The February 2012 Digital Edition of General Surgery News

The Society of Gastrointestinal and Endoscopic Surgeons

Convention issue:

®

GeneralsurGerynews.Com

The Independent Monthly Newspaper for the General Surgeon F ebruary 2012 • V olume 39 • Number 2

opinion

The Medical Arms Race

Study Asks: How Informed Should Your Patients Be? Surgeons’ Outcomes Matter to Patients; Legal Obligations in Flux

b y J oN c. W hite , mD

T

he term “mad” has always had numerous uses, but during the 1960s Cold War, it became popular as an acronym— MAD—shorthand for “mutually assured destruction.” It referred to the bizarre logic of the nuclear arms race, whereby the United States and the Soviet Union kept building up their nuclear arsenals to equal and then exceed the opposition, presumably as a deterrent to aggression. Eventually, the size of the arms buildups reached a point at which either country could destroy the other many times over. This policy was truly deserving of its ominous yet descriptive acronym.

Today, there is a similar situation in medicine that has appropriately been named “the medical arms race,” whereby competing hospitals or medical systems try to purchase the most up-to-date equipment and technology, which then can be used as a marketing ploy to compete for patients. Insurers do not question the provision of these services but

San FranciSco—Should surgeons disclose their volumes and outcomes during the informed consent process?

For years, it’s been a question hotly debated by surgeons, patients and jurists. Legally, there’s no resolution on the matter.

Now, the results of a new survey presented at the 2011 Clinical Congress of the American College of Surgeons suggest that surgeons do have an ethical obligation to disclose information about their experience during informed consent discussions. The disclosure

MedInfoNow Subscription see page 51

b y K ate o’r ourKe

LAP-BAND! SAFE 1 HOUR, FDA APPROVED 1-800-GETTHIN,” the billboard reads, featuring a fit blonde woman standing on a scale, flexing her biceps and flashing a wide smile.

San antonio—Doctors now have additional evidence that axillary lymph node dissection (ALND) does not add benefit to sentinel lymph node resection in clinically node-negative breast cancer patients with minimal sentinel node involvement. These results come from an update of the Phase III International Breast Cancer Study Group (IBCSG) trial 23-01. The study was reported at the San Antonio Breast Cancer Symposium (SABCS; abstract S3-1).

“Our findings are consistent with those of the ACOSOG Z-11 trial,” said Viviana Galimberti, MD, of the European Institute of Oncology in Milan, referring to the study conducted by the American College of Surgeons Oncology Group (ACOSOG). That randomized trial, first presented at the 2010 annual meeting of the American Society of Clinical Oncology, showed no benefit from ALND in clinically node-negative patients with one or two positive sentinel nodes. Since then, surgeons have gradually been adopting the more conservative approach to surgery. Dr. Galimberti said the two trials together should change clinical practice.

Patients eligible for the IBCSG 23-01 trial had clinically node-negative

see FDA GAstric BAnD page 10

see AxillAry page 22

see inForMeD consent page 14

FDA Squeezes Centers for Improper Promotion of Gastric Banding Deceitful Practices Target Patients Who May Not Need Surgery b y V ictoria S terN

I

Book page

No Benefit in Node-Negative Breast Cancer Patients

b y c hriStiNa F raNgou

see MAD page 38

More Evidence Against Axillary Dissection

f you live in California, perhaps you’ve noticed a billboard along the highway promoting weight loss with a safe, one-hour procedure that can be scheduled simply by calling a 1-800 number: “LOSE WEIGHT WITH THE

INSIDE

In the News

On the Spot

Opinion

From Napkin Sketch to FDA Approval: Developing Devices Challenging Yet Meaningful .................... 4

On the Spot: Treating the Sportsman’s Hernia; Gut Reaction on Various Topics in Surgery ......................... 26

Money for Drugs: Should Physicians Be Paid for Pharmaceutical Development and Clinical Research .......... 40

Gsn editorial 3

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

Thoughts of a Sailor Frederick L. Greene, MD Chairman, Department of General Surgery Carolinas Medical Center Charlotte, N.C.

O

ne of the memorable experiences of my life was my time as a Berry Planner, serving as a medical officer in the U.S. Navy after my surgical training. For those too young to remember the Berry Plan, this was a process by which medical students could select the branch of military service in which they would like to serve for two years after completing a portion of or all of their surgical training.

I selected the Navy and was fortunate to be assigned to the USS Nimitz, which was the first of the Nimitz-class nuclear carriers. In the mid-1970s, this ship was truly the showplace of the Navy.

The experience also provided me many interesting insights during the eight months I cruised the Mediterranean.

I remember many days and nights standing on the hanger deck, gazing out and watching both calm and rough seas.

I found that looking out at the water

had a calming effect, but also could be frightening when we noted 12- to 15-foot swells that many times kept us from disembarking at our ports of call. Because of the massive size of the ship, we never even felt the movement.

This was a good thing because during the operations that I performed on the Nimitz, the ship’s motion was not a contraindication to attempting surgical procedures. I also was amazed how, whether in calm conditions or severe storms, the ship’s navigation personnel could manipulate this behemoth of a vessel through rather confined spaces such as the Straits of Gibraltar and the narrow channels between Italy and Sicily.

My shipboard experience has helped me in many areas involving my work with patients and my administrative duties throughout the years. My recollection of my Navy experience and the admiration that I had for those who steered the ship conjure up one of my favorite sayings—“smooth seas do not make skillful sailors.” I actually keep this maxim on a sticky note on the top of my desk and reflect almost daily on its wisdom.

it would be delightful to have each day be free of any rocky encounters, but i must say this potentially would be quite boring!

All of us would like to have a nice stress-free existence, especially in our dealings with patients and the perioperative issues that we face. The same can be said for our interactions with medical colleagues, administrators, office staff, the bureaucracy in general and all of the intrigues that we face in our daily lives. The realization, however, is that if everything worked well and

Joseph J. Pietrafitta, MD Minneapolis, MN General Surgery, Laparoscopy, Colon and Rectal Surgery, Laser Surgery

Los Angeles, CA General Surgery, Laparoscopy, Surgical Education

Gary Hoffman, MD

Barry A. Salky, MD

Editorial Advisory Board

Los Angeles, CA Colorectal Surgery

New York, NY Laparoscopy

Maurice E. Arregui, MD

Namir Katkhouda, MD

Paul Alan Wetter, MD

Kay Ball, RN, CNOR, FAAN

Los Angeles, CA Laparoscopy

Miami, FL Ob/Gyn, Laparoscopy

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Lewis Center, OH Nursing

Youngstown, OH General Surgery, Laparoscopy

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Norfolk, VA General Surgery, Trauma/Critical Care

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Springfield, MA General Surgery, Laparoscopy

James Forrest Calland, MD Philadelphia, PA General Surgery, Trauma Surgery

Edward Felix, MD

Fresno, CA General Surgery, Laparoscopy

Robert J. Fitzgibbons Jr., MD Omaha, NE General Surgery, Laparoscopy, Surgical Oncology

David R. Flum, MD, MPH Seattle, WA General Surgery, Outcomes Research

Michael Goldfarb, MD Long Branch, NJ Laparoscopy, Telemedicine

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see sAilor page 6

David M. Reed, MD

Senior Medical Adviser

seamlessly, we would never have any challenges, and would never know how to deal with those thorny issues that life throws in our path. If the water were smooth on every occasion, we would learn to navigate without a problem; but once those ripples occur and the swells turn into raging seas, we might be lost and not able to find our way through those narrow straits.

mission statement It is the mission of General Surgery News to be an independent and reliable source of news and analysis about the current state of surgery. It strives to provide a venue for discussion and opinions, from all viewpoints, on the issues most important to surgeons.

Disclaimer Opinions and statements published in General Surgery News are those of the individual author or speaker and do not necessarily represent the views of the editorial advisory board, editorial staff or reporters.

INFECTIOUS DISEASE SPECIAL EDITION

4

in the news

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

From Napkin Sketch to FDA Approval: Developing Devices Successful Surgeon-inventors Provide Pearls of Wisdom b y g abriel m iller San antonio—The process of generating innovative technologies in surgery is difficult territory to traverse.

Surgeons who wish to develop new products face complex demands and challenges. For instance, technology has never been more central to surgery but devices are more expensive and time-consuming to bring to market than ever before.

At the 2011 annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), successful surgeon-inventors provided advice on how prospective innovators can navigate these issues and take their ideas from the drawing board to the operating room table.

determining whether or not the idea should be patented and protected as intellectual property. The purpose of intellectual property protection—trademarking, copyrighting and patenting, among many others—is to exclude others from an idea, or in this case a device concept, while that idea is given value.

“An idea, in and of itself, has absolutely no value,” said Thomas Fogarty, MD, professor of surgery at Stanford in Palo Alto, Calif., who manages several medical device companies and founded the venture capital firm Three Arch Partners. “Implementation of the idea is where the value lies.”

Henry Joseph Runge, JD, a senior licensing specialist at UNeMed Corporation, which handles technology transfer for the University of Nebraska Medical Center, agreed, adding that, “Even the really good ideas are still going to need a lot of improvement, especially in surgery because there is so much regulatory burden.”

to Develop or not to Develop, that is the Question Assuming that a surgical device can achieve its intended goal, there are still a number of nonclinical factors that have to be assessed before proceeding. One factor is whether the device has the potential to draw enough funding for development and, ultimately, for FDA approval.

“If you want to get funding, you need an idea that you can actually raise [funding] for,” said Raymond Onders, MD, chair of Surgical Innovation at University Hospitals Case Medical Center in Cleveland, Ohio. “Do you really have something that’s different and that’s going to work? And then you have to look at how much work is involved.”

Whether a device is “different” or “unique” typically has to do with its potential market or market share. For example, Dr. Onders has developed a device that stimulates the diaphragm electrically, allowing patients who might otherwise require a ventilator to breathe on their own. Although the market for the device, the NeuRx DPS, is relatively small, for patients with spinal cord injuries or Lou Gehrig’s disease the product represents a clear and significant advance. When determining the market for a device, “You have to look at all the applications of your technology,” said Dr. Onders.

Within this context, surgeons also should think about the cost of the device and whether or not it will be adopted within the culture of surgery, said Jeffrey Ponsky, MD, chairman of Surgery at Case Western Reserve University School of Medicine in Cleveland.

For example, a device that requires a technique or approach that most surgeons are not familiar with will never gain traction. “If the people who you want to use your device don’t have that skill, don’t design the device for them,” said Dr. Ponsky, who co-developed the percutaneous endoscopic gastrostomy catheter with Michael W.L. Gauderer, MD, at Rainbow Babies and Children’s Hospital in Cleveland.

Provided a market exists, the next step is

’an idea, in and of itself, has absolutely no value. implementation of the idea is where the value lies.’

—Thomas Fogarty, MD

Value for a device is created through the development, commercialization and regulatory process, which, broadly speaking, involves creating a prototype, testing it in the laboratory and ultimately demonstrating it in clinical, in-patient trials. And that takes money, a lot of money.

“There are always new rules with the FDA to get your device through a trial. You really have to know how much money it takes to do this,” said Dr. Onders.

raising money Inventors speaking on the topic at SAGES all provided similar advice on how to take that first step in device development: Get a partner with a business background to serve as CEO. “Most of us physicians are not true businessmen,” said Dr. Onders. “You need somebody who can write a business plan, talk to accountants and be a spokesperson for your idea.”

Surgeons can be particularly hard-headed on this point, said Dr. Fogarty. “Surgeons are used to being in charge,” he said. “You can’t do that with a team, particularly with engineers. They know things that you will not know. The physician does not bring the total value.”

A business plan is key, Dr. Onders added.

They are time-consuming and not necessarily easy to write. A partner with a background in business can articulate the long-range vision of the company and serve as its face during the fundraising and regulatory processes.

For many inventors, early funding typically comes from the “three Fs,” Dr. Onders said: friends, family and fools. Early funding also may come from angel investors, wealthy retired entrepreneurs or executives who provide start-up capital to businesses in exchange for ownership equity and tax benefits and who also, in some cases, gain social status by being affiliated with socially conscious projects.

There are, however, many other often overlooked options. Most cities and some states provide local assistance to start-up businesses that may bring jobs to the community, particularly cities hit hard by the economic recession. Likewise, the federal government also offers economic assistance to small businesses through the Small Business Innovation Research program. Additionally, there are many business plan competitions around the country that not only offer financial rewards for winning plans but also give entrepreneurs the chance to receive free advice from established business leaders as well as an opportunity to network with potential investors.

Early advice from other entrepreneurs and angel investors can go a long way during the more complicated stages of raising capital in later development.

“If you can get somebody in your local community to give you guidance, that will actually help you before you meet the venture capital sharks,” said Dr. Onders.

Early seed funding is used for preliminary business operations like market research and see Device page 7

In certain patients with MRSA* cSSSI† In certain patients with MRSA* cSSSI†

THE INFECTION INFECTION THE SCREAMS SCREAMS

‘ZYVOX’ ‘ZYVOX’ (linezolid IV/oral) IV/oral) (linezolid

With more than 10 years of experience treating cSSSI With more thanor 10suspected years of experience treatingZYVOX cSSSI for its: due to known MRSA, consider due to known or suspected MRSA, consider ZYVOX for its: – Established efficacy1 – Established efficacy1 – 100% bioavailable oral and IV formulations2 – 100% bioavailable oral and IV formulations2 – Excellent tissue penetration3 – Excellent tissue penetration3

*Methicillin-resistant Staphylococcus aureus. *Methicillin-resistant Staphylococcus aureus. † † Complicated skinskin andand skin structure infection.

Complicated skin structure infection.

INDICATIONS INDICATIONS ZYVOX formulations areareindicated ZYVOX formulations indicatedininthe thetreatment treatmentofof thethe following infections following infectionscaused causedbybysusceptible susceptiblestrains strains of ofthethedesignated designatedmicroorganisms. microorganisms. ZYVOX ZYVOX isis not not indicated treatment Gram-negativeinfections. infections. indicated forfor thethe treatment ofof Gram-negative criticalthat thatspecifi specifi Gram-negativetherapy therapy be be It It is iscritical c cGram-negative initiated immediately concomitantGram-negative Gram-negative initiated immediately if if a aconcomitant pathogen is documented suspected. pathogen is documented oror suspected.

Complicatedskin skinand andskin skinstructure structureinfections, infections, Complicated including diabetic diabetic foot foot infections, infections, without without including concomitant osteomyelitis,caused causedbybyStaphylococcus Staphylococcus concomitant osteomyelitis, aureus(methicillin-susceptible (methicillin-susceptibleand and-resistant -resistant strains), strains), aureus Streptococcus pyogenes,ororStreptococcus Streptococcusagalactiae. agalactiae.

Streptococcus pyogenes, ZYVOXhashasnot notbeen beenstudied studiedininthe the treatment treatment ofof ZYVOX decubitus ulcers. decubitus ulcers.

Uncomplicatedskin skinand andskin skinstructure structure infections infections Uncomplicated caused byby Staphylococcus Staphylococcus aureus aureus (methicillin(methicillincaused susceptible only) Streptococcuspyogenes. pyogenes. susceptible only) oror Streptococcus reduce development drug-resistantbacteria bacteria To To reduce thethe development ofofdrug-resistant and maintain the effectiveness of ZYVOX and other and maintain the effectiveness of ZYVOX and other antibacterial drugs, ZYVOX should be used only to antibacterial drugs, ZYVOX should be used only to treat or prevent infections that are proven or strongly treat or prevent thatby aresusceptible proven or strongly suspected to infections be caused bacteria. suspected to be caused by susceptible bacteria.

When culture and susceptibility information are When culture susceptibility information available, theyand should be considered in selectingareor available, they should be considered selecting or modifying antibacterial therapy.

In the in absence of such modifying antibacterial therapy.

In the absence of such data, local epidemiology and susceptibility patterns may data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. contribute to the empiric selection of therapy.

IMPORTANT SAFETY INFORMATION IMPORTANT SAFETY INFORMATION ZYVOX use is contraindicated in patients with known ZYVOX use is contraindicated in patients with product known hypersensitivity to linezolid or any of the other hypersensitivity components. to linezolid or any of the other product components.

ZYVOX should not be used in patients taking any ZYVOX should notwhich be used in monoamine patients taking any medicinal product inhibits oxidases medicinal product which isocarboxazid) inhibits monoamine oxidases A or B (e.g. phenelzine, or within 2 weeks A or (e.g. any phenelzine, isocarboxazid) or within 2 weeks of Btaking such product.

Unless are monitored for potential increases of taking anypatients such product. inUnless bloodpatients pressure, should be administered areZYVOX monitored fornot potential increases in blood pressure, ZYVOX should not be administered

to hypertension, to patients patients with with uncontrolled uncontrolled hypertension, pheochromocytoma, and/or patients patients pheochromocytoma, thyrotoxicosis thyrotoxicosis and/or taking directly and andindirectly indirectlyacting acting takingany anyof ofthe the following: following: directly sympathomimetic, and dopaminergic dopaminergic sympathomimetic, vasopressive, and agents. agents.

Unlesspatients patients are are carefully observed Unless observed for forsigns signsand/or and/or symptomsof ofserotonin serotonin syndrome, ZYVOX symptoms ZYVOXshould shouldnot notbe be administered to to patients patients with carcinoid administered carcinoid syndrome syndromeand/ and/ or patients patients taking taking any any of the following or following medications: medications: serotonin reuptake reuptake inhibitors, tricyclic serotonin tricyclic antidepressants, antidepressants, serotonin 5-HT1 5-HT1 receptor receptor agonists, serotonin agonists, meperidine, meperidine, orbuspirone. buspirone. or Spontaneous reports reports of of serotonin Spontaneous serotonin syndrome syndrome have have beenreported reported with with the the coadministration coadministration of been of ZYVOX ZYVOXand and serotonergic agents. agents. IfIf signs signs or serotonergic or symptoms symptoms of of serotonin serotonin syndrome, such such as as cognitive cognitive dysfunction, syndrome, dysfunction, hyperpyrexia, hyperpyrexia, hyperreflexia, exia, and and incoordination incoordination occur, hyperrefl occur, discontinuation discontinuation ofone oneor orboth both agents agents should should be of be considered. considered.

Myelosuppression (including (including anemia, Myelosuppression anemia, leukopenia, leukopenia, pancytopenia, and thrombocytopenia) has been reported pancytopenia, and thrombocytopenia) has been reported in patients receiving ZYVOX. In cases where the outcome inispatients receiving ZYVOX. In cases where the outcome known, when ZYVOX was discontinued, the affected ishematologic known, whenparameters ZYVOX wasreturned discontinued, the affected to pretreatment hematologic parameters returned to pretreatment levels. Complete blood counts should be monitored levels. countswho should be ZYVOX monitored weekly,Complete particularlyblood in patients receive for weekly, particularly in patients who receive ZYVOX for longer than 2 weeks. longer thanis2not weeks.

ZYVOX approved and should not be used for the ZYVOX isofnot approved should not be used for the treatment patients withand catheter-related bloodstream treatment with infections. catheter-related bloodstream infections of or patients catheter-site infections catheter-site infections.

ZYVOXor has no clinical activity against Gram-negative ZYVOX has no isclinical activity against pathogens and not indicated for theGram-negative treatment of pathogens and is not indicated for the that treatment Gram-negative infections.

It is critical specifiof c Gram-negative infections.

It is critical that specifi Gram-negative therapy be initiated immediately if ac Gram-negative therapy be initiated immediately if a concomitant Gram-negative pathogen is documented concomitant or suspected.Gram-negative pathogen is documented or suspected.

Clostridium difficile associated diarrhea has been Clostridium associated diarrhea has been reported with diffi usecile of nearly all antibacterial agents, including with ZYVOX, range severity from mild reported useand of may nearly all in antibacterial agents, diarrhea to fatal colitis. including ZYVOX, and may range in severity from mild diarrhea to fatal colitis.

Lactic acidosis acidosishas hasbeen beenreported reportedwith withthetheuseuse Lactic ZYVOX. Patients Patientsreceiving receivingZYVOX ZYVOXwho whodevelop develop ofof ZYVOX. recurrentnausea, nausea,vomiting, vomiting,unexplained unexplained acidosis, recurrent acidosis, or or a a lowbicarbonate bicarbonatelevel levelshould should receive immediate medical low receive immediate medical evaluation. evaluation.

Peripheral have been reported Peripheraland andoptic opticneuropathy neuropathy have been reported primarily with ZYVOX forfor longer than primarilyininpatients patientstreated treated with ZYVOX longer than the 2828 days.

If If themaximum maximumrecommended recommendedduration durationof of days. patients symptoms ofof visual impairment, patientsexperience experience symptoms visual impairment, prompt is is recommended. promptophthalmic ophthalmicevaluation evaluation recommended.

Convulsions in in patients treated Convulsionshave havebeen beenreported reported patients treated with these cases, a history of of seizures withZYVOX. ZYVOX.InInsome someofof these cases, a history seizures ororrisk was reported. riskfactors factorsfor forseizures seizures was reported.

The in in The most mostcommonly commonlyreported reportedadverse adverseevents events adults clinical trials were diarrhea, nausea, adultsacross acrossphase phase3 3 clinical trials were diarrhea, nausea, and andheadache. headache.

REFERENCES: REFERENCES:1.1.Itani ItaniK,K,Dryden DrydenMS, MS,Bhattacharyya Bhattacharyya H, EffiEffi cacy and H,Kunkel KunkelMJ, MJ,Baruch BaruchAM, AM,Weigelt WeigeltJA.JA. cacy and safety of linezolid versus vancomycin for the treatment safety of linezolid versus vancomycin for the treatment of complicated skin and soft-tissue infections proven of complicated skin and soft-tissue infections proven to be caused by methicillin-resistant Staphylococcus to be caused by methicillin-resistant aureus.

Am J Surg.

2010;199(6):804-816. Staphylococcus 2. Welshman aureus.

Surg. 2010;199(6):804-816.

2. Welshman IR, SissonAm TA,JJungbluth GL, Stalker DJ, Hopkins NK. IR, Sisson TA, Jungbluth GL, Stalker DJ, NK. Linezolid absolute bioavailability and theHopkins effect of Linezolid absolute bioavailability andDrug the Dispos. effect of food on oral bioavailability.

Biopharm food on oral bioavailability.

Biopharm DrugG,Dispos.

2001;22(3):91-97.

3. Majcher-Peszynska J, Haase Sass 2001;22(3):91-97.

3. Majcher-Peszynska J, Haase G, Sass M, et al. Pharmacokinetics and penetration of linezolid M, et Pharmacokinetics and penetration of linezolid into inflal. amed soft tissue in diabetic foot infections.

Eur amed soft2008;64(11):1093-1100. tissue in diabetic foot infections. Eur Jinto Clininfl Pharmacol.

J Clin Pharmacol. 2008;64(11):1093-1100.

Please see brief summary on adjacent pages.

Please see brief summary on adjacent pages.

6

Gsn editorial Sailor

continued from page 3 We know that life is not a smooth sea.

If we think about the activities that we perform everyday, there are multiple ups and downs that we deal with and we do learn to become “skillful sailors” when we meet and navigate those encounters that potentially might capsize us. It would be delightful to have each day be free of any rocky encounters, but I must say this potentially would be quite boring! We become “skillful sailors”

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

’if we can transcend and maneuver through these types of issues then ultimately we can face most any challenge that is thrown in our way.’ when we learn early in our careers to navigate those choppy waters.

A detailed plan or algorithm for navigation is not innate. We have to decipher this on our own through trial

and error. Our experiences as surgeons, both in and out of the operating room, coalesce to make us more skillful as we face a tough surgical dilemma, a potentially noncompliant patient or a disruptive colleague whose mission is to make us miserable. All of these opportunities potentially can help us as we navigate through life. Again, if everything were smooth and joyful we would never learn how to handle those issues that create chaos and disruption.

I think it is also important to use these examples of “rough seas” as we work with our junior partners and

ZYVOX® linezolid injection, tablets and for oral suspension Brief summary of prescribing information.

INDICATIONS AND USAGE ZYVOX formulations are indicated in the treatment of the following infections caused by susceptible strains of the designated microorganisms (see PRECAUTIONS, Pediatric Use). Vancomycin-Resistant Enterococcus faecium infections, including cases with concurrent bacteremia. Nosocomial pneumonia caused by Staphylococcus aureus (methicillin-susceptible and -resistant strains), or Streptococcus pneumoniae (including multidrug-resistant strains [MDRSP*]). Complicated skin and skin structure infections, including diabetic foot infections, without concomitant osteomyelitis, caused by Staphylococcus aureus (methicillin-susceptible and -resistant strains), Streptococcus pyogenes, or Streptococcus agalactiae. ZYVOX has not been studied in the treatment of decubitus ulcers. Uncomplicated skin and skin structure infections caused by Staphylococcus aureus (methicillin-susceptible only) or Streptococcus pyogenes. Community-acquired pneumonia caused by Streptococcus pneumoniae (including multidrug-resistant strains [MDRSP*]), including cases with concurrent bacteremia, or Staphylococcus aureus (methicillin-susceptible strains only).

To reduce the development of drug-resistant bacteria and maintain the effectiveness of ZYVOX and other antibacterial drugs, ZYVOX should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.

When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

CONTRAINDICATIONS ZYVOX formulations are contraindicated for use in patients who have known hypersensitivity to linezolid or any of the other product components.

ZYVOX should not be used in patients taking any medicinal product which inhibits monoamine oxidases A or B (e.g. phenelzine, isocarboxazid) or within 2 weeks of taking any such medicinal product. Unless patients are monitored for potential increases in blood pressure, ZYVOX should not be administered to patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis and/or patients taking any of the following types of medications: directly and indirectly acting sympathomimetic agents (e.g. pseudoephedrine), vasopressive agents (e.g. epinephrine, norepinephrine), and dopaminergic agents (e.g. dopamine, dobutamine). Unless patients are carefully observed for signs and/or symptoms of serotonin syndrome, ZYVOX should not be administered to patients with carcinoid syndrome and/or patients taking any of the following medications: serotonin re-uptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), meperidine, or buspirone.

WARNINGS Myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) has been reported in patients receiving ZYVOX. In cases where the outcome is known, when ZYVOX was discontinued, the affected hematologic parameters have risen toward pretreatment levels. Complete blood counts should be monitored weekly in patients who receive ZYVOX, particularly in those who receive ZYVOX for longer than two weeks, those with pre-existing myelosuppression, those receiving concomitant drugs that produce bone marrow suppression, or those with a chronic infection who have received previous or concomitant antibiotic therapy.

Discontinuation of therapy with ZYVOX should be considered in patients who develop or have worsening myelosuppression. In adult and juvenile dogs and rats, myelosuppression, reduced extramedullary hematopoiesis in spleen and liver, and lymphoid depletion of thymus, lymph nodes, and spleen were observed. Mortality Imbalance in an Investigational Study in Patients With Catheter-related Bloodstream Infections, Including Those With Catheter-site Infections. ZYVOX is not approved and should not be used for the treatment of patients with catheter-related bloodstream infections or catheter-site infections. In an open-label investigational study in seriously ill patients with intravascular catheter-related infections, an imbalance in mortality was seen in patients treated with ZYVOX compared with vancomycin/dicloxacillin/oxacillin.

While causality has not been established, mortality was higher in patients treated with ZYVOX who were infected with Gram-negative organisms alone, with both Grampositive and Gram-negative organisms, or who had no infection when they entered the study. Patients with Gram-positive infections had no difference in mortality. ZYVOX has no clinical activity against Gram-negative pathogens and is not indicated for the treatment of Gram-negative infections. It is critical that specific Gram-negative therapy be initiated immediately if a concomitant Gram-negative pathogen is documented or suspected. Clostridium difficile–associated diarrhea (CDAD) has been reported with the use of nearly all antibacterial agents, including ZYVOX, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C difficile. C difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing strains of C difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur more than 2 months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C difficile, and surgical evaluation should be instituted as clinically indicated.

PRECAUTIONS General Lactic acidosis has been reported with the use of ZYVOX. In reported cases, patients experienced repeated episodes of nausea and vomiting.

Patients who develop recurrent nausea or vomiting, unexplained acidosis, or a low bicarbonate level while receiving ZYVOX should receive immediate medical evaluation.

Spontaneous reports of serotonin syndrome associated with the co-administration of ZYVOX and serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs), have been reported (see PRECAUTIONS, Drug Interactions).

Where administration of ZYVOX and concomitant serotonergic agents is clinically appropriate, patients should be closely observed for signs and symptoms of serotonin syndrome such as cognitive dysfunction, hyperpyrexia, hyperreflexia and incoordination. If signs or symptoms occur physicians should consider discontinuation of either one or both agents. If the concomitant serotonergic agent is withdrawn, discontinuation symptoms can be observed (see package insert of the specified agent(s) for a description of the associated discontinuation symptoms). Peripheral and optic neuropathy have been reported in patients treated with ZYVOX, primarily those patients treated for longer than the maximum recommended duration of 28 days. In cases of optic neuropathy that progressed to loss of vision, patients were treated for extended periods beyond the maximum recommended duration. Visual blurring has been reported in some patients treated with ZYVOX for less than 28 days.

If patients experience symptoms of visual impairment, such as changes in visual acuity, changes in color vision, blurred vision, or visual field defect, prompt ophthalmic evaluation is recommended. Visual function should be monitored in all patients taking ZYVOX for extended periods (≥3 months) and in all patients reporting new visual symptoms regardless of length of therapy with ZYVOX. If peripheral or optic neuropathy occurs, the continued use of ZYVOX in these patients should be weighed against the potential risks. Convulsions have been reported in patients treated with ZYVOX. In some of these cases, a history of seizures or risk factors for seizures was reported. The use of antibiotics may promote the overgrowth of nonsusceptible organisms. Should superinfection occur during therapy, appropriate measures should be taken. ZYVOX has not been studied in patients with uncontrolled hypertension, pheochromocytoma, carcinoid syndrome, or untreated hyperthyroidism. The safety and efficacy of ZYVOX formulations given for longer than 28 days have not been evaluated in controlled clinical trials. Prescribing ZYVOX in the absence of a proven or

our residents to explain that there are potential “silver linings” even in worstcase scenarios. If we can transcend and maneuver through these types of issues then ultimately we can face most any challenge that is thrown in our way. Yes, it is my contention that our skills as physicians, administrators and human beings are enhanced when we have challenges. Indeed, smooth seas do not make skillful sailors or good physicians.

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We would like your opinion.

Please send letters to: khorty@mcmahonmed.com.

strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Information for Patients Patients should be advised that: ZYVOX may be taken with or without food. They should inform their physician if they have a history of hypertension. Large quantities of foods or beverages with high tyramine content should be avoided while taking ZYVOX. Quantities of tyramine consumed should be less than 100 mg per meal. Foods high in tyramine content include those that may have undergone protein changes by aging, fermentation, pickling, or smoking to improve flavor, such as aged cheeses (0 to 15 mg tyramine per ounce); fermented or air-dried meats (0.1 to 8 mg tyramine per ounce); sauerkraut (8 mg tyramine per 8 ounces); soy sauce (5 mg tyramine per 1 teaspoon); tap beers (4 mg tyramine per 12 ounces); red wines (0 to 6 mg tyramine per 8 ounces). The tyramine content of any protein-rich food may be increased if stored for long periods or improperly refrigerated. They should inform their physician if taking medications containing pseudoephedrine HCl or phenylpropanolamine HCl, such as cold remedies and decongestants. They should inform their physician if taking serotonin re-uptake inhibitors or other antidepressants.

Phenylketonurics: Each 5 mL of the 100 mg/5 mL ZYVOX for Oral Suspension contains 20 mg phenylalanine. The other ZYVOX formulations do not contain phenylalanine.

Contact your physician or pharmacist. They should inform their physician if they experience changes in vision. They should inform their physician if they have a history of seizures. Diarrhea is a common problem caused by antibiotics, which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible. Patients should be counseled that antibacterial drugs including ZYVOX should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When ZYVOX is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by ZYVOX or other antibacterial drugs in the future. Drug Interactions Monoamine Oxidase Inhibition: Linezolid is a reversible, nonselective inhibitor of monoamine oxidase. Therefore, linezolid has the potential for interaction with adrenergic and serotonergic agents. Adrenergic Agents: Some individuals receiving ZYVOX may experience a reversible enhancement of the pressor response to indirectacting sympathomimetic agents, vasopressor or dopaminergic agents. Commonly used drugs such as phenylpropanolamine and pseudoephedrine have been specifically studied. Initial doses of adrenergic agents, such as dopamine or epinephrine, should be reduced and titrated to achieve the desired response. Serotonergic Agents: Coadministration of linezolid and serotonergic agents was not associated with serotonin syndrome in Phase 1, 2 or 3 studies. Spontaneous reports of serotonin syndrome associated with co-administration of ZYVOX and serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs), have been reported. Patients who are treated with ZYVOX and concomitant serotonergic agents should be closely observed as described in the PRECAUTIONS, General Section. DrugLaboratory Test Interactions There are no reported drug-laboratory test interactions.

Pregnancy Teratogenic Effects. Pregnancy Category C: Linezolid was not teratogenic in mice, rats, or rabbits at exposure levels 6.5-fold (in mice), equivalent to (in rats), or 0.5-fold (in rabbits) the expected human exposure level, based on AUCs. However, embryo and fetal toxicities were seen (see Non-teratogenic Effects). There are no adequate and well-controlled studies in pregnant women. ZYVOX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Non-teratogenic Effects In mice, embryo and fetal toxicities were seen only at doses that caused maternal toxicity (clinical signs and reduced body weight gain). A dose of 450 mg/kg/day (6.5-fold the estimated human exposure level based on AUCs) correlated with increased postimplantational embryo death, including total litter loss, decreased fetal body weights, and an increased incidence of costal cartilage fusion. In rats, mild fetal toxicity was observed at 15 and 50 mg/kg/day (exposure levels 0.22-fold to approximately equivalent to the estimated human exposure, respectively based on AUCs). The effects consisted of decreased fetal body weights and reduced ossification of sternebrae, a finding often seen in association with decreased fetal body weights.

Slight maternal toxicity, in the form of reduced body weight gain, was seen at 50 mg/ kg/day. In rabbits, reduced fetal body weight occured only in the presence of maternal toxicity (clinical signs, reduced body weight gain and food consumption) when administered at a dose of 15 mg/kg/day (0.5-fold the estimated human exposure based on AUCs). When female rats were treated with 50 mg/kg/day (approximately equivalent to the estimated human exposure based on AUCs) of linezolid during pregnancy and lactation, survival of pups was decreased on postnatal days 1 to 4. Male and female pups permitted to mature to reproductive age, when mated, showed an increase in preimplantation loss. Nursing Mothers Linezolid and its metabolites are excreted in the milk of lactating rats. Concentrations in milk were similar to those in maternal plasma.

It is not known whether linezolid is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ZYVOX is administered to a nursing woman. Pediatric Use The safety and effectiveness of ZYVOX for the treatment of pediatric patients with the following infections are supported by evidence from adequate and well-controlled studies in adults, pharmacokinetic data in pediatric patients, and additional data from a comparator-controlled study of Gram-positive infections in pediatric patients ranging in age from birth through 11 years (see INDICATIONS AND USAGE): nosocomial pneumonia, complicated skin and skin structure infections, community-acquired pneumonia (also supported by evidence from an uncontrolled study in patients ranging in age from 8 months through 12 years), vancomycin-resistant Enterococcus faecium infections. The safety and effectiveness of ZYVOX for the treatment of pediatric patients with the following infection have been established in a comparator-controlled study in pediatric patients ranging in age from 5 through 17 years: uncomplicated skin and skin structure infections caused by Staphylococcus aureus (methicillin-susceptible strains only) or Streptococcus pyogenes.

Pharmacokinetic information generated in pediatric patients with ventriculoperitoneal shunts showed variable cerebrospinal fluid (CSF) linezolid concentrations following single and multiple dosing of linezolid; therapeutic concentrations were not consistently achieved or maintained in the CSF. Therefore, the use of linezolid for the empiric treatment of pediatric patients with central nervous system infections is not recommended. The Cmax and the volume of distribution (Vss) of linezolid are similar regardless of age in pediatric patients. However, linezolid clearance is a function of age. Excluding neonates less than a week of age, clearance is most rapid in the youngest age groups ranging from >1 week old to 11 years, resulting in lower singledose systemic exposure (AUC) and shorter half-life as compared with adults. As age of pediatric patients increases, the clearance of linezolid gradually decreases, and by adolescence, mean clearance values approach those observed for the adult population.

There is wider inter-subject variability in linezolid clearance and in systemic drug exposure (AUC) across all pediatric age groups as compared with adults. Similar mean daily AUC values were observed in pediatric patients from birth to 11 years of age dosed q8h relative to adolescents or adults dosed q12h. Therefore, the dosage for pediatric patients up to 11 years of age should be 10 mg/kg q8h. Pediatric patients 12 years and older should receive 600 mg q12h. Recommendations for the dosage regimen for pre-term neonates less than 7 days of age (gestational age less than 34 weeks) are based on pharmacokinetic data from 9 pre-term neonates. Most of these pre-term neonates have lower systemic linezolid clearance values and larger AUC

in the news 7

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

Device

continued from page 4 product development; after a device has been established as potentially viable, funding may then come from venture capital firms, which typically fund companies during their growth phase when they may not be able to secure bank loans.

Venture capital financing typically has three or four stages, each with its own set of rules, but the primary underlying point is that unlike raising debt

or taking a loan from a lender, venture capital is invested in exchange for an equity stake in the business. Invariably, a business owner’s equity will decrease with each round of financing, but that process—known as dilution—can be managed. “[Venture capitalists] want to know how much you want and you have to be very careful,” said Dr. Onders. “If they think you have a great idea and are only asking for $2 million, and they say ‘Yeah, it’s a winner, we’ll give you $10 million,’ you’re valuation didn’t change and now they just own you. If somebody

values than many full-term neonates and older infants. Therefore, these pre-term neonates should be initiated with a dosing regimen of 10 mg/kg q12h. Consideration may be given to the use of a 10 mg/kg q8h regimen in neonates with a sub-optimal clinical response. All neonatal patients should receive 10 mg/kg q8h by 7 days of life. In limited clinical experience, 5 out of 6 (83%) pediatric patients with infections due to Gram-positive pathogens with MICs of 4 μg/mL treated with ZYVOX had clinical cures.

However, pediatric patients exhibit wider variability in linezolid clearance and systemic exposure (AUC) compared with adults. In pediatric patients with a sub-optimal clinical response, particularly those with pathogens with MIC of 4 μg/mL, lower systemic exposure, site and severity of infection, and the underlying medical condition should be considered when assessing clinical response. Geriatric Use Of the 2046 patients treated with ZYVOX in Phase 3 comparator-controlled clinical trials, 589 (29%) were 65 years or older and 253 (12%) were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.

ADVERSE REACTIONS Adult Patients The safety of ZYVOX formulations was evaluated in 2046 adult patients enrolled in seven Phase 3 comparator-controlled clinical trials, who were treated for up to 28 days. In these studies, 85% of the adverse events reported with ZYVOX were described as mild to moderate in intensity. The incidence (%) of adverse events reported in at least 2% of patients treated with either ZYVOX (n=2046) or all comparators† (n=2001) in these trials were as follows: diarrhea 8.3 and 6.3; headache 6.5 and 5.5; nausea 6.2 and 4.6; vomiting 3.7 and 2.0; insomnia 2.5 and 1.7; constipation 2.2 and 2.1; rash 2.0 and 2.2; dizziness 2.0 and 1.9; and fever 1.6 and 2.1 respectively. The most common adverse events in patients treated with ZYVOX were diarrhea (incidence across studies: 2.8% to 11.0%), headache (incidence across studies: 0.5% to 11.3%), and nausea (incidence across studies: 3.4% to 9.6%). The percent of drug-related adverse events in at least 1% of adult patients in a trial involving the treatment of uncomplicated skin and skin structure infection comparing ZYVOX 400 mg q12h (n=548) to clarithromycin 250 mg q12h (n=537) were 25.4 and 19.6 respectively. The percent of patients discontinuing drug due to drug-related adverse events‡ were 3.5 and 2.4 respectively. The incidence of drug-related adverse events occurring in >1% of adult patients were diarrhea 5.3 and 4.8; nausea 3.5 and 3.5; headache 2.7 and 2.2; taste alteration 1.8 and 2.0; vaginal moniliasis 1.6 and 1.3; fungal infection 1.5 and 0.2; abnormal liver function tests 0.4 and 0.0; vomiting 0.9 and 0.4; tongue discoloration 1.1 and 0.0; dizziness 1.1 and 1.5; and oral moniliasis 0.4 and 0.0 respectively. The percent of drug-related adverse events in at least 1% of adult patients in all other indications of ZYVOX 600 mg q12h (n=1498) versus all other comparators§ (n=1464) with at least 1 drugrelated adverse event was 20.4 and 14.3 respectively. The percent of adult patients discontinuing due to drug-related adverse events‡ was 2.1 and 1.7 respectively. The incidence of drug-related adverse events occurring in >1% of adult patients were diarrhea 4.0 and 2.7; nausea 3.3 and 1.8; headache 1.9 and 1.0; taste alteration 0.9 and 0.2; vaginal moniliasis 1.0 and 0.4; fungal infection 0.1 and <0.1; abnormal liver function tests 1.3 and 0.5; vomiting 1.2 and 0.4; tongue discoloration 0.2 and 0.0; dizziness 0.4 and 0.3; and oral moniliasis 1.1 and 0.4. Other adverse events reported in Phase 2 and Phase 3 studies included oral moniliasis, vaginal moniliasis, hypertension, dyspepsia, localized abdominal pain, pruritus, and tongue discoloration. Pediatric Patients The safety of ZYVOX formulations was evaluated in 215 pediatric patients ranging in age from birth through 11 years, and in 248 pediatric patients aged 5 through 17 years (146 of these 248 were age 5 through 11 and 102 were age 12 to 17). These patients were enrolled in two Phase 3 comparator-controlled clinical trials and were treated for up to 28 days. In these studies, 83% and 99%, respectively, of the adverse events reported with ZYVOX were described as mild to moderate in intensity. In the study of hospitalized pediatric patients (birth through 11 years) with Gram-positive infections, who were randomized 2 to 1 (linezolid:vancomycin), mortality was 6.0% (13/215) in the linezolid arm and 3.0% (3/101) in the vancomycin arm. However, given the severe underlying illness in the patient population, no causality could be established. The incidence of adverse events reported in ≥2% of pediatric patients treated for uncomplicated skin and skin structure infections|| with ZYVOX (n=248) or cefadroxil (n= 251) were fever 2.9 and 3.6; diarrhea 7.8 and 8.0; vomiting 2.9 and 6.4; rash 1.6 and 1.2; headache 6.5 and 4.0; upper respiratory infection 3.7 and 5.2; nausea 3.7 and 3.2; trauma 3.3 and 4.8; pharyngitis 2.9 and 1.6; cough 2.4 and 4.0; generalized abdominal pain 2.4 and 2.8; localized abdominal pain 2.4 and 2.8; loose stools 1.6 and 0.8; localized pain 2.0 and 1.6; skin disorder 2.0 and 0.0 respectively. The incidence of adverse events reported in ≥2% of pediatric patients treated for all other indications¶ with either ZYVOX (n=215) or vancomycin (n=101) in comparator-controlled trials were fever 14.1 and 14.1; diarrhea 10.8 and 12.1; vomiting 9.4 and 9.1; sepsis 8.0 and 7.1; rash 7.0 and 15.2; headache 0.9 and 0.0; anemia 5.6 and 7.1; thrombocytopenia 4.7 and 2.0; upper respiratory infection 4.2 and 1.0; nausea 1.9 and 0.0; dyspnea 3.3 and 1.0; reaction at site of injection or of vascular catheter 3.3 and 5.1; trauma 2.8 and 2.0; pharyngitis 0.5 and 1.0; convulsion 2.8 and 2.0; hypokalemia 2.8 and 3.0; pneumonia 2.8 and 2.0; thrombocythemia 2.8 and 2.0; cough 0.9 and 0.0; generalized abdominal pain 0.9 and 2.0; localized abdominal pain 0.5 and 1.0; apnea 2.3 and 2.0; gastrointestinal bleeding 2.3 and 1.0; generalized edema 2.3 and 1.0; loose stools 2.3 and 3.0; localized pain 0.9 and 0.0; and skin disorder 0.9 and 1.0. The percent of pediatric patients treated for uncomplicated skin and skin structure infections|| with either ZYVOX (n=248) or cefadroxil (n=251) and with ≥1 drug-related adverse event occurring in more than 1% of patients were 19.2 and 14.1 respectively. The percent of pediatric patients discontinuing due to a drug-related adverse event was 1.6 and 2.4 respectively.

The incidence of drug-related adverse events reported in more than 1% of pediatric patients (and more than 1 patient) were diarrhea 5.7 and 5.2; nausea 3.3 and 2.0; headache 2.4 and 0.8; loose stools 1.2 and 0.8; vomiting 1.2 and 2.4; generalized abdominal pain 1.6 and 1.2; localized abdominal pain 1.6 and 1.2; eosinophilia 0.4 and 0.4; rash 0.4 and 1.2; vertigo 1.2 and 0.4 and pruritus at non-application site 0.4 and 0.0 respectively. The percent of pediatric patients treated for all other indications¶ with either ZYVOX (n=215) or vancomycin (n=101) and with ≥1 drug-related adverse event occurring in more than 1% of patients were 18.8 and 34.3 respectively. The percent of patients discontinuing due to a drug-related adverse event were 0.9 and 6.1 respectively. The incidence of drug-related adverse events reported in more than 1% of pediatric patients (and more than 1 patient) were diarrhea 3.8 and 6.1; nausea 1.4 and 0.0; loose stools 1.9 and 0.0; thrombocytopenia 1.9 and 0.0; vomiting 1.9 and 1.0; anemia 1.4 and 1.0; eosinophilia 1.4 and 0.0; rash 1.4 and 7.1; oral moniliasis 0.9 and 4.0; fever 0.5 and 3.0; pruritus at non-application site 0.0 and 2.0; and anaphylaxis 0.0 and 10.1# respectively. Laboratory Changes ZYVOX has been associated with thrombocytopenia when used in doses up to and including 600 mg every 12 hours for up to 28 days. In Phase 3 comparator-controlled trials, the percentage of adult patients who developed a substantially low platelet count (defined as less than 75% of lower limit of normal and/or baseline) was 2.4% (range among studies: 0.3 to 10.0%) with ZYVOX and 1.5% (range among studies: 0.4 to 7.0%) with a comparator. In a study of hospitalized pediatric patients ranging in age from birth through 11 years, the percentage of patients who developed a substantially low platelet count (defined as less than 75% of lower limit of normal and/or baseline) was 12.9% with ZYVOX and 13.4% with vancomycin. In an outpatient study of pediatric patients aged from 5 through 17 years, the percentage of patients who developed a substantially low platelet count was 0% with ZYVOX and 0.4% with cefadroxil. Thrombocytopenia associated with the use of ZYVOX appears to be dependent on duration of therapy, (generally greater than 2 weeks of treatment). The platelet counts for most patients returned to the normal range/baseline during the follow-up period. No related clinical adverse events were ZVU428507-01

© 2012 Pfizer Inc.

All rights reserved.

offers you a lot more money, think in the back of your mind, why are they offering me more money than I need?”

Physicians, Dr. Onders said, should be forewarned that it is unwise to think that financiers won’t know as much about the field as they do.

“You have to be careful,” he said.

“You may think, ‘Oh, I’m a doctor,’ but these guys are not stupid. They know the background, they may already have invested in your competitor; they know what they are doing. ... If you are passionate about this, you have to try and maintain some control.”

identified in Phase 3 clinical trials in patients developing thrombocytopenia. Bleeding events were identified in thrombocytopenic patients in a compassionate use program for ZYVOX; the role of linezolid in these events cannot be determined (see WARNINGS).

Changes seen in other laboratory parameters, without regard to drug relationship, revealed no substantial differences between ZYVOX and the comparators. These changes were generally not clinically significant, did not lead to discontinuation of therapy, and were reversible. The percent of adult patients with at least one substantially abnormal hematologic** value in patients treated with ZYVOX 400 mg q12h or clarithromycin 250 mg q12h for uncomplicated skin and skin structure infections were as follows: hemoglobin (g/dL) 0.9 and 0.0; platelet count (x 103/mm3) 0.7 and 0.8; WBC (x 103/mm3) 0.2 and 0.6; neutrophils (x 103/mm3) 0.0 and 0.2 respectively. The percent of adult patients with at least one substantially abnormal hematologic** value in patients treated with ZYVOX 600 mg q12h or a comparator§ were as follows: hemoglobin (g/dL) 7.1 and 6.6; platelet count (x 103/mm3) 3.0 and 1.8; WBC (x 103/mm3) 2.2 and 1.3 and neutrophils (x 103/mm3) 1.1 and 1.2 respectively. The percent of adult patients with at least one substantially abnormal serum chemistry†† value in patients treated with ZYVOX 400 mg q12h or clarithromycin 250 mg q12h for uncomplicated skin and skin structure infections were as follows: AST (U/L) 1.7 and 1.3; ALT (U/L) 1.7 and 1.7; LDH (U/L) 0.2 and 0.2; alkaline phosphatase (U/L) 0.2 and 0.2; lipase (U/L) 2.8 and 2.6; amylase (U/L) 0.2 and 0.2; total bilirubin (mg/dL) 0.2 and 0.0; BUN (mg/dL) 0.2 and 0.0; and creatinine (mg/dL) 0.2 and 0.0 respectively. The percent of adult patients with at least one substantially abnormal serum chemistry†† value in patients treated with ZYVOX 600 mg q12h or a comparator§ were as follows: AST (U/L) 5.0 and 6.8; ALT (U/L) 9.6 and 9.3; LDH (U/L) 1.8 and 1.5; alkaline phosphatase (U/L) 3.5 and 3.1; lipase (U/L) 4.3 and 4.2; amylase (U/L) 2.4 and 2.0; total bilirubin (mg/dL) 0.9 and 1.1; BUN (mg/dL) 2.1 and 1.5; and creatinine (mg/dL) 0.2 and 0.6 respectively. The percent of pediatric patients with at least one substantially abnormal hematologic‡‡ value in patients treated with ZYVOX or cefadroxil for uncomplicated skin and skin structure infections|| were as follows: hemoglobin (g/dL) 0.0 and 0.0; platelet count (x 103/mm3) 0.0 and 0.4; WBC (x 103/mm3) 0.8 and 0.8; neutrophils (x 103/mm3) 1.2 and 0.8 respectively. The percent of pediatric patients with at least one substantially abnormal hematologic‡‡ value in patients treated with ZYVOX or vancomycin for any other indication¶ were as follows: hemoglobin (g/dL) 15.7 and 12.4; platelet count (x 103/mm3) 12.9 and 13.4; WBC (x 103/ mm3) 12.4 and 10.3 and neutrophils (x 103/mm3) 5.9 and 4.3 respectively. The percent of pediatric patients with at least one substantially abnormal serum chemistrya value in patients treated with ZYVOX or cefadroxil for uncomplicated skin and skin structure infections|| were as follows: ALT (U/L) 0.0 and 0.0; lipase (U/L) 0.4 and 1.2; and creatinine (mg/dL) 0.4 and 0.0 respectively. The percent of pediatric patients with at least one substantially abnormal serum chemistrya value in patients treated with ZYVOX or vancomycin for any other indication¶ were as follows: ALT (U/L) 10.1 and 12.5; amylase (U/L) 0.6 and 1.3; total bilirubin (mg/dL) 6.3 and 5.2; and creatinine (mg/dL) 2.4 and 1.0 respectively. Postmarketing Experience Myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) has been reported during postmarketing use of ZYVOX (see WARNINGS). Peripheral neuropathy, and optic neuropathy sometimes progressing to loss of vision, have been reported in patients treated with ZYVOX. Lactic acidosis has been reported with the use of ZYVOX (see PRECAUTIONS). Although these reports have primarily been in patients treated for longer than the maximum recommended duration of 28 days, these events have also been reported in patients receiving shorter courses of therapy. Serotonin syndrome has been reported in patients receiving concomitant serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and ZYVOX (see PRECAUTIONS). Convulsions have been reported with the use of ZYVOX (see PRECAUTIONS). Anaphylaxis, angioedema, and bullous skin disorders such as those described as Stevens Johnson syndrome have been reported. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to ZYVOX, or a combination of these factors. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made and causal relationship cannot be precisely established. OVERDOSAGE In the event of overdosage, supportive care is advised, with maintenance of glomerular filtration. Hemodialysis may facilitate more rapid elimination of linezolid. In a Phase 1 clinical trial, approximately 30% of a dose of linezolid was removed during a 3-hour hemodialysis session beginning 3 hours after the dose of linezolid was administered.

Data are not available for removal of linezolid with peritoneal dialysis or hemoperfusion.

Clinical signs of acute toxicity in animals were decreased activity and ataxia in rats and vomiting and tremors in dogs treated with 3000 mg/kg/day and 2000 mg/kg/day, respectively. * MDRSP refers to isolates resistant to 2 or more of the following antibiotics: penicillin, second-generation cephalosporins, macrolides, tetracycline, and trimethoprim/ sulfamethoxazole. † Comparators included cefpodoxime proxetil 200 mg PO q12h; ceftriaxone 1 g IV q12h; clarithromycin 250 mg PO q12h; dicloxacillin 500 mg PO q6h; oxacillin 2 g IV q6h; vancomycin 1 g IV q12h. ‡ The most commonly reported drug-related adverse events leading to discontinuation in patients treated with ZYVOX were nausea, headache, diarrhea, and vomiting. § Comparators included cefpodoxime proxetil 200 mg PO q12h; ceftriaxone 1 g IV q12h; dicloxacillin 500 mg PO q6h; oxacillin 2 g IV q6h; vancomycin 1 g IV q12h. || Patients 5 through 11 years of age received ZYVOX 10 mg/kg PO q12h or cefadroxil 15 mg/kg PO q12h. Patients 12 years or older received ZYVOX 600 mg PO q12h or cefadroxil 500 mg PO q12h. ¶ Patients from birth through 11 years of age received ZYVOX 10 mg/kg IV/PO q8h or vancomycin 10 to 15 mg/kg IV q6-24h, depending on age and renal clearance. # These reports were of ‘red-man syndrome,’ which were coded as anaphylaxis. ** <75% (<50% for neutrophils) of Lower Limit of Normal (LLN) for values normal at baseline; <75% (<50% for neutrophils) of LLN and of baseline for values abnormal at baseline. †† >2 x Upper Limit of Normal (ULN) for values normal at baseline; >2 x ULN and >2 x baseline for values abnormal at baseline. ‡‡ <75% (<50% for neutrophils) of Lower Limit of Normal (LLN) for values normal at baseline; <75% (<50% for neutrophils) of LLN and <75% (<50% for neutrophils, <90% for hemoglobin if baseline <LLN) of baseline for values abnormal at baseline. a >2 x Upper Limit of Normal (ULN) for values normal at baseline; >2 x ULN and >2 (>1.5 for total bilirubin) x baseline for values abnormal at baseline.

Rx only Rev. May 2008

’you can be in a situation where you spend a year, even two years, trying to get a clinical trial going and by the time you get it going, it’s no longer available.’

—Jeffrey Ponsky, MD Throughout the funding process, the business will have to demonstrate that it is hitting milestones in development, chiefly in the form of laboratory testing and regulatory submissions. This is the stepwise progression from prototype to approved commercial device.

From idea to Clinical use Surgeons can use a device off-label at any point, but if they plan to study it in patients in order to add value through research, the device then requires regulatory approval at some level.

“When you use a new tool today, you can do anything you want,” said Dr. Ponsky. “But if you’re going to publish and you’re going to study it, you need IRB [institutional review board] approval.”

Typically this is done at an academic medical center and, here again, it is important to remember that the institution will likely gain some equity as a result.

“You may think, ‘I did this myself while I was here at my university, I own it and I’m going to be a millionaire.

Slow down,” Dr. Ponsky said. “Normally, if you work at an institution and it’s paying you a salary, the institution has some skin in the game. Understand what your contract is with your employer and with your commercial [sponsor].”

It’s important, Dr. Ponsky added, that regardless of the type of device or stage in testing, that study results be published. “If you have an interesting device, write it up so you stamp your foot there,” he said. As an example Dr. Ponsky points to natural orifice transluminal endoscopic surgery (NOTES).

At meetings, he’s frequently cited as an inventor of the procedure, even though Indian surgeons actually developed the surgical techniques.

“I have the first published NOTES paper in the whole world in a human. It is nonsense,” he said, “but nobody else wrote it up.”

The role of IRBs is a contentious one among device developers.

Many centers require approval from a number of committees, which can slow down and even halt the development of a product. “You can be in a situation see Device page 8

January 2012

8

in the news Device

Continued from page 7 where you spend a year, even two years, trying to get a clinical trial going and by the time you get it going, it’s no longer available. Some other institution has already done it,” Dr. Fogarty said.

The business of clinical trials has also changed dramatically, reaching billions of dollars for some devices. In the 1960s, Dr. Fogarty said he brought a device to market—doing research that he said was equivalent to today’s FDA requirements—for $30,000. Currently, one device he’s involved with has cost $2 billion and the technology is still not available in the United States.

’this is a lot of fun when you have a good idea.

Don’t be discouraged, get involved in this process and have some fun with it. But get the advice of people who’ve done it before.’

—Jeffrey Ponsky, MD The key difference here is whether a device is “substantially equivalent to one legally in commercial distribution” or a “premarket device” requiring an investigational device exemption. In layman’s terms: Is it an improvement of an existing device or is it doing something no one has ever done before?

All devices coming to market, whether they are equivalent or investigational, are categorized by the FDA as class I, II or III depending on the degree of risk to patients. The difference in regulatory effort and costs between bringing a “substantially equivalent class I device” to market versus those associated with an “investigational class III device” are enormous, probably to the point that they can’t be overstated.

“It’s very important to understand how the FDA is looking at you,” Dr. Onders said.

Dr. Fogarty added, “The cost of innovation in the medical device and drug area currently is not sustainable in the U.S. At the end of the day it has become very, very expensive and there are many, many buckets. But one of the biggest buckets is clinical trials.”

’never, never Give up’ Successful innovators are quick to enumerate the difficulties of bringing a device to market, but they are just as quick to point out that it is incredibly meaningful and downright enjoyable. Some find it so important they’re willing to mortgage their home to fund

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

a fledgling company, as Dr. Onders has.

“This is a lot of fun when you have a good idea,” said Dr. Ponsky.

“Don’t be discouraged; get involved in this process and have some fun with it. But get the advice of people who’ve done it before.”

Dr. Fogarty, who has some 80 patents to his name and has cofounded more than 30

start-up device companies, said that despite the growing regulatory barriers, now “is a time to be amazed” by innovation in medicine. The first step, he said, is imagination. “I don’t say things won’t work anymore because everything that I said wouldn’t work is in the process of working or has already worked,” he said.

“The message is never, never give up,” he said.

“You’ve got to have fun but

if you say you’re going to do something you’ve got to do it. Be prepared to handle failure, because at steps along the way you will fail, but you have to be persistent and you have to be passionate.”

Disclosures: Dr. Fogarty reported receiving royalties from Covidien, Medtronic and Tyco. Dr. Onders reported an ownership interest in Synapse Biomedical. Dr. Ponsky reported receiving honoraria as a consultant for US Endoscopy. Dr. Runge reported no relevant financial or commercial relationships.

in the news 9

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

Seeing the (Green) Light In the Operating Room Researchers Take On Poor Visibility During Surgery b y J ohN D illoN

O

perating rooms that are too dark should go green, according to a new study that purposely sheds little light on a safety issue.

The research, presented at the 2011 annual meeting of the American Society

of Anesthesiologists [abstract 1660], found that rather than shutting off the overhead fixtures in the OR—a common practice that gives surgeons the clearest view of monitors—bathing the room in a dim green light accomplishes the same goal more safely and without forcing others to feel as if they are working in a tomb.

“Surgeons depend on excellent image quality from their monitors,” said Julian Goldman, MD, medical director of

biomedical engineering at Partners Healthcare System in Boston. “Historically we have turned off the OR light to achieve that. They want high contrast and low glare.” That’s no different, he said, from anyone who prefers the house lights out in a movie theater, but surgeons cannot afford to experience “washout” on a monitor during a laparoscopic procedure.

But what’s good for the surgeon is not necessarily ideal for others in the

From top: Ambient room, green room, white room.

OR, including the patient. “There are a lot of hazards in the operating room,” said Kirk Shelley, MD, PhD, professor of anesthesiology at the Yale School of Medicine, in New Haven, Conn., and immediate past-president of the Society for Technology in Anesthesia. “One of them is tripping hazards. Also, there’s stuff overhead. You need a certain amount of light. We’re keeping anesthesia records. You have to take notes.

You have to read the bottles.” Anesthesiologists and other personnel use desk lamps and flashlights to see what they are doing when lighting is low.

Dr. Goldman was aware of previous experiments using green light, so he launched a pilot project for minimally invasive procedures in the “Operating Room of the Future” at Massachusetts General Hospital (MGH), in Boston, where he is principal anesthesiologist.

The solution was decidedly low-tech— and cheap.

Operating rooms often are too bright.

The two ORs where the trial was held had nine fluorescent fixtures. The light meter reading with the white lights on was nearly 1,800 lux; with the lights off, see Green liGht page 30

10

in the news FDa gaStric BanD continued from page 1

But not so fast. On Dec. 13, the FDA issued warning letters to eight surgical centers in California and one marketing firm regarding the misleading advertisements about gastric banding.

“The warning was issued because the Los Angeles County Public Health Department submitted a request that the FDA investigate the promotion of Lap-Band,” said Morgan Liscinsky, press officer at the FDA Office of

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

Public Affairs.

Warning letters were sent to Bakersfield Surgery Institute Inc., Beverly Hills Surgery Center, Palmdale Ambulatory Surgery Center, Valley Surgical Center, Top Surgeons LLC, Valencia Ambulatory Center LLC, Cosmopolitan Plastic & Reconstructive Surgery, San Diego Ambulatory Center LLC and 1 800 GET THIN LLC. In the letters, the FDA cautioned that billboards and advertising inserts used by these companies to promote the gastric band failed to provide required risk information, including warnings,

precautions, possible side effects and contraindications.

“The FDA takes seriously its responsibility to protect consumers from products promoted without adequate warnings,” said Steve Silverman, director of the Office of Compliance in the FDA’s Center for Devices and Radiological Health, in an FDA press statement. “It’s particularly troublesome when advertisements don’t communicate the serious risks associated with medical devices.”

For example, one of the advertising inserts claims: “LET YOUR NEW

on Dec. 13, the FDa issued a warning to eight surgical centers in California and one marketing firm regarding misleading lap-Band advertisements, such as the one depicted in this billboard along interstate 5 in Commerce, Calif.

Photo: Glenn Koenig/los angeles times.

Copyright, 2011, los angeles times. reprinted with permission.

LIFE BEGIN!” followed by a photograph of woman with the caption: “I LOST 130 POUNDS.” Below the photograph, in “very small print” the FDA said, is information related to risks. Below the risk information, in “very large font,” business operating hours are listed: “CALL NOW! 1-800-GET-THIN HOURS: 6:30AM - 10PM.” “FDA’s concern is that these ads glamorize the Lap-Band without communicating any of the risks,” Mr. Silverman said. “Consumers, who may be influenced by misleading advertising, need to be fully aware of the risks of any surgical procedure.”

In warning letters to the surgical centers and marketing firm, the FDA stated that the marketing of the Lap-Band by these businesses violates the Federal Food, Drug and Cosmetic Act. The agency’s “approval of the Lap-Band restricted this device by requiring that it only be sold and distributed upon authorization by a licensed practitioner (i.e., under prescription). Section 502(q) of the Act provides that a restricted device is misbranded if its advertising is false or misleading in any particular.”

The letters also stated that these “advertisements fail to reveal material facts, including relevant risk information regarding the use of the Lap-Band, age and other qualifying requirements for the Lap-Band procedure, and the need for ongoing modification of eating habits, as provided in the approved Lap-Band labeling.”

The FDA requested that the companies “immediately cease marketing

in the news 11

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

a big role in FDA’s decision to issue the warning letters. I’m sure this is something that FDA has been aware of for a while.”

Mr. Stearns added that, “Ultimately, this decision involves a balancing of the nature of the violations, the potential harm to the public, FDA’s limited resources and the expectation of voluntary compliance by the offending parties.”

Company responds to FDa Pressure 1 800 GET THIN issued an immediate response to the FDA warning on its Web site: “In response to the recent FDA letter

the Lap-Band using advertising that violates the Act” and that they “take prompt action to correct the violations addressed in this letter.” Failure to correct these violations promptly may cause the FDA to initiate regulatory actions against the companies, including seizure, injunction and civil money penalties.

FDa warning not the First Before the FDA issued the complaint, several lawsuits were filed against the companies in question. In one, relatives of two California women, who died within days of undergoing Lap-Band procedures at clinics linked to the 1 800 GET THIN marketing campaign, filed a false advertising complaint. Additionally, the plaintiffs alleged that Topsurgeons.com runs a call center, in which employees are paid a minimum wage plus a commission when they sell the company’s services, answer prospective patients’ routine questions about the Lap-Band and schedule surgical appointments.

“The existence of the lawsuits and the fact that the advertising is very blatant and directly to the public make this activity higher-profile than most,” said Frederick A. Stearns, JD, partner at the law firm Keller and Heckman LLP, who specializes in legal issues involving the regulation of drugs and medical devices. “FDA’s position about the lack of appropriate risk information is not unusual. The safety concerns coupled with the very public nature of the advertising certainly played

’the warning was issued because the los angeles County Public Health Department submitted a request that the FDa investigate the promotion of lap-Band.’

regarding 1 800 GET THIN advertisements, 1 800 GET THIN is committed to working with the FDA to resolve any outstanding issue,” the statement said.

“1 800 GET THIN does not provide medical services nor do they manufacture, distribute or sell the Lap Band medical device. All individuals who call 1-800-GET-THIN are referred to licensed physicians and accredited facilities where every individual will receive a full and complete disclosure of the risks and benefits of surgical weight loss,” the company said. “1 800 GET THIN has verified that prior to any surgical

procedure every potential surgical candidate will undergo a thorough medical evaluation which includes consultations with nutritionists, therapists and various independent medical doctors.”

In the FDA’s press release, the agency clarified that health care providers who choose to promote the gastric banding procedure are required to educate patients about the risks involved, which must also be included in any advertising and promotional materials.

“The decision to undergo a gastric banding procedure should be done in see FDA GAstric BAnD page 12

Less pain.

Less opioids.

OFIRMEV® provides significant pain relief*1 • OFIRMEV 1 g (Q6h) + patient-controlled analgesia (PCA) morphine demonstrated significant pain relief vs placebo + PCA morphine (P<0.05 over 6 h)1 • OFIRMEV 1 g (Q6h) + PCA morphine showed greater reduction in pain intensity over 24 h (SPID24)† compared to placebo + PCA morphine (P<0.001)2

OFIRMEV reduces opioid consumption*1 • OFIRMEV 1 g (Q6h) + PCA morphine significantly reduced morphine consumption vs placebo + PCA morphine (–46% over 6 h, P<0.01; –33% over 24 h, P<0.01)1 • The clinical benefit of reduced opioid consumption was not demonstrated

Schedule OFIRMEV Q6h for the first 24 h • Continue OFIRMEV or transition to PO analgesia based on patient assessment

Indication OFIRMEV is indicated for the management of mild to moderate pain; the management of moderate to severe pain with adjunctive opioid analgesics; and the reduction of fever.

Important Safety Information OFIRMEV is contraindicated in patients with severe hepatic impairment, severe active liver disease or with known hypersensitivity to acetaminophen or to any of the excipients in the formulation. Acetaminophen should be used with caution in patients with the following conditions: hepatic impairment or active hepatic disease, alcoholism, chronic malnutrition, severe hypovolemia, or severe renal impairment.

Do not exceed the maximum recommended daily dose of acetaminophen.

Administration of acetaminophen by any route in doses higher than recommended may result in hepatic injury, including the risk of severe hepatotoxicity and death.

OFIRMEV should be administered only as a 15-minute intravenous infusion.

Discontinue OFIRMEV immediately if symptoms associated with allergy or hypersensitivity occur. Do not use in patients with acetaminophen allergy.

The most common adverse reactions in patients treated with OFIRMEV were nausea, vomiting, headache, and insomnia in adult patients and nausea, vomiting, constipation, pruritus, agitation, and atelectasis in pediatric patients.

OFIRMEV is approved for use in patients ≥2 years of age.

The antipyretic effects of OFIRMEV may mask fever in patients treated for postsurgical pain.

To report SUSPECTED ADVERSE REACTIONS, contact Cadence Pharmaceuticals, Inc. at 1-877-647-2239 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.com.

Please see Brief Summary of Prescribing Information on adjacent page or full Prescribing Information at OFIRMEV.com.

*Randomized, double-blind, placebo-controlled, single- and repeated-dose 24-h study (n=101). Patients received OFIRMEV 1 g + PCA morphine or placebo + PCA morphine the morning following total hip or knee replacement surgery. Primary endpoint: pain relief measured on a 5-point verbal scale over 6 h.

Morphine rescue was administered as needed. †SPID24=sum of pain intensity differences, based on VAS score, from baseline, at 0 to 24 h.

References: 1. Sinatra RS, Jahr JS, Reynolds LW, Viscusi ER, Groudine SB, Payen-Champenois C. Efficacy and safety of single and repeated administration of 1 gram intravenous acetaminophen injection (paracetamol) for pain management after major orthopedic surgery. Anesthesiology. 2005;102:822-831.

2. Data on file. Cadence Pharmaceuticals, Inc.

—Morgan Liscinsky, FDA press officer ©2012 Cadence Pharmaceuticals, Inc. All rights reserved.

OFIRMEV and the OFIRMEV dot design are trademarks of Cadence Pharmaceuticals, Inc.

OFV11310112

OFIRMEV.com

12

in the news FDa gaStric BanD continued from page 11

close consultation between a patient and his or her health care provider,” said Kimber Richter, MD, deputy director for medical affairs in the Office of Compliance in the FDA’s Center for Devices and Radiological Health. “It is important for the patient to fully understand both the risks and the benefits of the procedure and for the health care provider to be sure the procedure is appropriate for the patient.”

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

For instance, patients must understand that gastric banding is used when nonsurgical weight loss methods have been unsuccessful. Patients considering gastric banding must be willing to make major changes in eating habits and lifestyle, and only those who can follow dietary and other health and lifestyle recommendations should consider the procedure.

surgeons respond to the Campaign Several surgeons responded to the misleading Lap-Band advertisements, reflecting on the ethics of promoting

surgical techniques to the public. ’FDa’s concern is that these ads Edward L. Felix, MD, stated that, “Competition is good for the glamorize the lap-Band without system and can give a procedure communicating any of the risks.’ more credibility. Ads let people —Steve Silverman know about the procedure. Cedar Sinai Hospital [in Los Angeles] advertises, we advertise. I don’t see Bariatric Program at Clovis Commuanything wrong with that.” nity Medical Center. “The difference “But this [Lap-Band] advertising here is if you do market and get peois doing the opposite and will lead to ple interested [in a procedure], you have a bad name for the procedure,” added to do so responsibly. Our hospital actuDr. Felix, assistant clinical professor of ally markets what bariatric and diabetic surgery, University of California, San surgery can do for the patient and what Francisco, and medical director of the the risks are.”

Walter J. Pories, MD, FACS, agreed with Dr. Felix that advertising, in general, is not a bad thing. “Although you might consider it distasteful, with our right to free speech, there isn’t a lot we can do about [advertising]. Medical boards who attempt to rule against [aggressive] advertising usually find doing so is a violation of free speech.”

“I’m not defending this [campaign],” added Dr. Pories, chief of the Metabolic Institute and professor of surgery at Brody School of Medicine, East Carolina University, Greenville, N.C. “But when you really look at things carefully, there’s a tremendous amount of false advertising on TV, especially for weight loss products. Very few actually work and most people know they don’t work.”

Robin Blackstone, MD, FACS, FASMBS, president of the American Society for Metabolic & Bariatric Surgery (ASMBS), commented on the questionable principles of the gastric band advertisers. “This massive advertising campaign has been problematic, partly because bariatric surgery is a serious surgical therapy for very serious metabolic diseases, namely diabetes, and the ads, which portray surgery as a cosmetic solution, does not do bariatric surgery justice.”

“Some advertising can be balanced and fair with a good educational message that ultimately leaves the decision to be made between the surgeon and patients. However, these ads seem to give people the impression that somehow [gastric banding] is not surgery and it doesn’t make them aware of all the options. That’s a disservice to the public and one that is being recognized by the FDA,” added Dr. Blackstone, medical director of Scottsdale Healthcare Bariatric Center at Scottsdale Healthcare in Arizona, and clinical associate professor of surgery at the University of Arizona College of Medicine.

Dr. Blackstone acknowledged that, “It’s been frustrating for the Society to not have better ways to address this [misleading advertising] because the surgeons involved are not members of our society and so they do not come

in the news 13

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

’this massive advertising campaign has been problematic, partly because bariatric surgery is a serious surgical therapy for very serious metabolic diseases, namely diabetes, and the ads, which portray surgery as a cosmetic solution, does not do bariatric surgery justice.’

lot of money and then realize it’s all a scam.”

Additionally, all eight facilities mentioned in the FDA warning letters are owned and operated by the same group of physicians. If you browse the list of physicians on Palmdale Ambulatory Surgery Center’s Web site (http://palmdale-asc.com/physicians.html) and then on Bakersfield Surgery Institute Inc. (http://bakersfield-surgery.com/physicians.html), you will encounter many of the same names.

As reported in a March 4 2010 LA Times article, an inspection report of

Almont Ambulatory Surgery Center, issued in June 2010, included 22 pages of violations. For instance, inspectors found unsanitary conditions in surgical areas, surgical instruments that were not properly disinfected as well as expired or missing medications and supplies to treat complications from anesthesia.

“It’s difficult when surgeons work outside the society’s ethics and rules,” said Dr. Blackstone. “People can practice all types of surgeries in surgical centers and for the most part they practice high quality procedures; however, these centers have to acknowledge to the

public that surgery centers are not regulated like hospitals. And each state has an obligation to make patients aware of the level of regulation and oversight that’s done in these centers.”

The FDA encourages consumers and health care professionals who suspect a problem with a gastric banding device to file a voluntary report through MedWatch, the FDA Safety Information and Adverse Event Reporting program.

For more information about the FDA warning, visit www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ ucm283455.htm.

—Robin Blackstone, MD

under our ethics guidelines. We also do not have access to the information that we would need, like medical records and data on the centers to determine the circumstances of the problems. The regulatory federal and state authorities who do have that information need to act in such a way that they can protect the public.”

Dr. Felix noted that although he thinks the “FDA was right” to issue these warning letters, nothing will likely come of it. “The companies will change their number and their name and continue to advertise.” Case in point, “Instead of decreasing, the ads are spreading north.

They are metastasizing, moving up to San Francisco and beyond.”

Beyond the advertisements It appears that the FDA may have only scratched the surface of these gastric band ads by issuing its warning letters. The misleading ads are just the beginning of the problem.

After calling 1-800-GET-THIN, potential patients are “farmed out” to one of the eight surgical centers.

According to an article published in LA Times on Feb. 14 2010, TopSurgeons convinced a patient during an office visit to apply for a special credit card offered by a branch of General Electric Co. in order to check her credit.

The patient was approved within hours and several weeks later received a bill for $15,000 from General Electric for a surgery that she decided against after consulting with an outside physician.

The con doesn’t end here. “These centers also often put patients through a huge workup, which may include sleep studies, a cardiac workup and endoscopy even if there is no medical indication for the study,” said Dr. Felix. “The patients end up with a huge bill before they even get the surgery and some don’t end up having the procedure at all. Patients who go through this can get very discouraged. They can spend a

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Schedule subject to change.While clinical studies support the use of the daVinci Surgical System as an effective tool for minimally invasive surgery, individual results may vary. Before performing any clinical procedure utilizing the System, physicians are responsible for receiving sufficient training and proctoring to ensure that they have the requisite training,skill,and experience necessary to protect the health and safety of the patient.For technical information,including full cautions and warnings on using the da Vinci System, please refer to the System User Manual. Read all instructions carefully. Failure to properly follow instructions, notes, cautions and warnings associated with this equipment may lead to serious injury or complications for the patient. Presentations are not intended to substitute for formal medical training or certification. Intuitive Surgical trains only on the use of its products. © 2012 Intuitive Surgical. All rights reserved. Intuitive, Intuitive Surgical, da Vinci, da Vinci S HD, da Vinci Si, InSite, TilePro, Single-Site and EndoWrist are trademarks or registered trademarks of Intuitive Surgical. All other product names are trademarks or registered trademarks of their respective holders. PN 875814 Rev A 1/12

14

in the news

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

inFormeD conSent continued from page 1

may one day be legally mandated in some jurisdictions, said the study authors.

In a survey of more than 380 patients, nearly 80% said that they believe a surgeon’s experience is essential information that patients need in order to make an informed decision about elective surgery.

Lead author Susan J. Lee Char, MD, a lawyer and general surgery resident at the University of California-San Francisco, said if patients feel they need to know about a surgeon’s volumes and outcomes,

then surgeons need to provide them that information.

“That information should include their own volumes and outcomes if accurate data are available, and whether it would be their first time performing the procedure,” she said.

At least half of U.S. states use a “reasonable patient standard”—what a reasonable patient would need to know in order to make an informed decision about surgery—to define what should be disclosed during informed consent.

The findings raise the possibility that in states where courts used a reasonable

patient standard to define the scope of disclosure, a surgeon’s volumes and outcomes also may become legally mandated, said Dr. Lee Char.

Interestingly, the 85 surgeons who completed the same survey felt differently than the patients: Only 55% thought that this information was essential to patient decision making.

The study hits on a long-standing debate in surgery about whether surgeons should be required to disclose their volumes and outcomes when obtaining informed consent.

George Chang, MD, associate

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1 Twardowski ZJ et al “Intraabdominal Pressures during Natural Activities in Patients Treated with Continuous Ambulatory Peritoneal Dialysis” Nephron 44:129-135 1986. Cobb WS et al. “The Argument for Lightweight Polypropylene Mesh in Hernia Repair” Surgical Innovation. Vol 12 (1).63-69, 2005.

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surgeons often lack accurate data on their volumes and outcomes or accurate comparisons for how their volumes and outcomes rate against those of other surgeons. professor of surgery and director of clinical operations for the Minimally Invasive and New Technologies in Oncologic Surgery Program, at the University of Texas MD Anderson Cancer Center in Houston, said the study shows a “disconnect” between what physicians think is important based on their understanding of data and what patients think is important based on their emotions and experiences.

“Clearly, there is an imbalance,” he said, adding the study will help define informed consent.

Surgeons have many valid concerns about disclosing their volumes and outcomes, said Dr. Lee Char. They often lack accurate data on their volumes and outcomes or accurate comparisons for how their volumes and outcomes rate against those of other surgeons. Such a process could make things extremely difficult for surgeons just starting out in practice because they have not amassed large volumes. Plus, there are additional fears that some patients may be deterred from surgeons with lower volumes even if their outcomes are good. So far, the courts have not established a standard for what must be disclosed during the informed consent process.

In half of U.S. states, courts use a “reasonable physician standard” as the basis for their decisions on what type of disclosure is necessary, meaning that information should be included if a reasonable physician believes it is relevant for a patient deciding whether to have surgery. The other half of U.S. states uses a reasonable patient standard to determine what is relevant.

Two main state cases have addressed the issue of whether surgeons must disclose their experience when obtaining informed consent and they came to contrary conclusions. In Johnson v. Kokemoor (1996), Donna Johnson brought a case against neurosurgeon Richard Kokemoor, MD, alleging that he failed to obtain her informed consent before surgery. Ms. Johnson underwent a maxillary artery clipping by Dr. Kokemoor; she became a quadriplegic. The Wisconsin Supreme Court found that informed consent was inadequate because, under the reasonable patient standard, the surgeon should have divulged his inadequate experience, compared morbidity and mortality between experienced and inexperienced surgeons and offered to refer the

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

patient to a tertiary care center with more experienced surgeons. The Court found that if a reasonable person in the patient’s position possessed this information before consenting to surgery, that person would have been better able to make an informed and intelligent decision.

Yet, the second major case to deal with

informed consent ruled differently. In Whiteside v. Lukson (1997), the defending surgeon had taken a two-day course in laparoscopic cholecystectomy. During those two days, he performed the procedure on three pigs. When he obtained consent for his first human laparoscopic cholecystectomy, he did not disclose that he had only previously done the procedure in pigs. After sustaining a bile duct injury, the patient sued for breach of informed consent. The Court of Appeals of Washington found that under the reasonable patient standard, the surgeon was not required to disclose his lack of experience

when obtaining informed consent.

With no clear rules on disclosing experience during informed consent, Dr. Lee Char and colleagues set out to answer two important questions: What types of information about volumes and outcomes are essential to patients deciding whether to have surgery? How do patients and surgeons differ on what information is important during the informed consent process?

The investigators surveyed 383 patients and 85 surgeons from the University of California-San Francisco and affiliated hospitals. The patients, who had already undergone surgery at the university, were

Next stop: GeneralSurgeryNews.com

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in the news 15 approximately two-thirds of patients considered their surgeon’s volumes/outcomes essential; only one-third of surgeons felt the same. questioned about a hypothetical case scenario involving a partial hepatectomy.

They were asked to use a six-point Likert scale to rate the importance of 16 different types of information that could be included in an informed consent discussion.

Results showed that, for patients, the single most important piece of information was if the surgeon would be performing the surgery for the first time (mean Likert score, 5.81). In all, 80% of patients considered this information essential to decision making.

Patients also felt that their surgeon’s volumes and outcomes were critical pieces of information, ranking these after risks– benefits in overall importance (mean Likert scores, 5.53 and 5.73, respectively).

Surgeons, however, felt their volumes/ outcomes and their previous number of cases were not as relevant to the informed consent process as discussion of risks and benefits. Approximately two-thirds of patients considered their surgeon’s volumes/outcomes essential to decision making, whereas only one-third of surgeons considered this information essential (Pearsons c2; P<0.001). Only 55% of surgeons felt it was essential to tell patients that it was the surgeon’s first time compared with 79% of patients (P<0.001).

The investigators also looked at whether patients’ concerns changed when their surgeon proposed using newer techniques.

Patients were asked to rate the importance of varying types of information for undergoing a partial hepatectomy by a standard open surgery, laparoscopic or robotic resection, each representing an increasing level of innovation. As the level of innovation increased, so did patients’ desire for information about their surgeon’s experience and training, results showed.

The least valued type of information dealt with conflicts of interest. Few patients and even fewer surgeons considered these topics critical or essential to decision making. About 50% of patients wanted to know if their surgeon was a paid consultant, whereas 40% of surgeons felt it was relevant. Only 27% of patients and 20% of surgeons felt it was relevant to disclose if the surgeon was doing research.

The study has several limitations. The results are based on a hypothetical case scenario and not an actual informed consent discussion. The study cohort was predominantly well educated and female, which may not reflect the general population.

16

surgeons’ lounge

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

Dear Readers, Welcome to the February issue of The Surgeons’ Lounge. This issue features Conrad H. Simpfendorfer, MD, director of hepatobiliary and pancreatic surgery in the Department of General and Vascular Surgery, Cleveland Clinic Florida, in Weston, as our guest expert. Dr. Simpfendorfer will review and discuss the case of a patient with a liver mass found during an elective laparoscopic cholecystectomy for repeated bouts of biliary colic.

Take the Surgeons’ Challenge, and see what our experts say about laparoscopic cholecystectomy as an outpatient procedure in the Expert Express!

We look forward to your comments and questions.

Sincerely, Samuel Szomstein, MD, FACS Editor, The Surgeons’ Lounge

Dr. Szomstein is associate director, Bariatric Institute, Section of Minimally Invasive Surgery, Department of General and Vascular Surgery, Cleveland Clinic Florida, Weston.

Dr. Simpfendorfer’s

Reply

Question for Dr. Simpfendorfer From Carlos Esquivel Sanatorio Allende, Cordoba, Argentina

A 57-year-old woman underwent elective laparoscopic cholecystectomy for repeated bouts of biliary colic. During surgery, a mass was found on the liver and a biopsy was performed (Figure).

Laparoscopic cholecystectomy was completed and no further intervention was done. The pathology report five days later revealed mesenchymal hamartoma.

What would you do now? As I have no expertise in liver surgery, was my management appropriate? Would you have done anything differently during elective laparoscopic cholecystectomy considering your expertise in liver surgery? How frequent are incidental masses in the liver during elective laparoscopic cholecystectomy?

Mesenchymal hamartoma of the liver (MHL) is an uncommon benign tumor that mainly appears in childhood, and accounts for about 3% to 8% of all primary tumors in childhood.

The condition is extremely rare in adults: Less than 5% of cases of MHL occur in patients older than 5 years, with fewer than 20 adult cases reported.

The pathophysiology of the disease remains unknown. For years, physicians have accepted that this disease is the result of a failure of the ductal plate to develop normally in utero, a reaction to biliary obstruction or even the result of regional ischemia. Recent

immunohistochemical and flow cytometry studies have suggested that MHL is a true neoplasm rather than a developmental anomaly, and that it may be the initial step or another stage in the development of an embryonal sarcoma of the liver.

Imaging methods that help establish the diagnosis most often include ultrasound and computed tomography (CT) or magnetic resonance imaging (MRI). Biopsy of the MHL usually demonstrates variable mixtures of liver tissues on histology. The predominant component is mesenchymal, and consists of loose connective tissue with cyst-like collections of fluid, dilated lymphatics and blood vessels and multiple branched and tortuous bile ducts.

Treatment most often is by surgical resection and depends on the state of the patient, the size of the tumor and

Figure. mass on liver seen during laparoscopic cholecystectomy.

its relation to surrounding structures.

Alternate treatments reported include embolization, and there have been three cases of liver transplantation.

In this case, the finding of a liver mass adjacent to the gallbladder at the time of laparoscopic cholecystectomy was incidental. The mass did not invade the gallbladder. A biopsy of the mass was obtained and the cholecystectomy was completed in a routine fashion, as I would have done. The incidence of tumors coincidentally recognized during laparoscopic cholecystectomy is unknown in the literature, but it is known that 0.5% of gallbladder carcinomas are found coincidentally during laparoscopic cholecystectomy, and approximately 70% of asymptomatic carcinoids are found during laparotomy or endoscopy.

During follow-up, I would obtain routine lab work including liver function test, a-fetoprotein, carcinoembryonic antigen and CA19-9. I would also recommend a triphasic liver CT or MRI to better evaluate the extent of the lesion and its relationship to hepatic structures. If the lesion is resectable, I would then determine if I am going to perform a laparoscopic resection or an open liver resection. Results with surgery are very good, with an extremely low incidence of recurrence.

Surgeon’s Challenge

A

79-year-old man with a known umbilical hernia presents with abdominal pain. To date, the patient has been able to self-reduce the hernia.

On presentation, there is a very hard, tender mass noted at the umbilical hernia site, which cannot be reduced in the emergency room. The patient is taken to the operating room, where a small midline laparotomy incision is placed about 5 cm above and 2 cm below the umbilicus. The hernia sac is opened and there is approximately 7 inches of incarcerated bowel with evidence of ischemia and suffering.

There is no necrosis; good peristalsis exists along the incarcerated segment of bowel; and after a brief observation period, the ischemic segment appears well perfused. A partial omentectomy is performed and the bowel, along with the remaining omentum,

is reduced back into the abdominal cavity. The hernia sac is excised. The defect is closed with polydioxanone interrupted sutures. On postoperative day 2, the patient’s abdomen is markedly distended, and a nasogastric tube is placed. The output is approximately 2.5 L over 24 hours. The white blood cell count is 8,000/cu mm with no shift, no fever and no abdominal pain. A computed tomography scan is ordered on postoperative day 3 and the impression is ileus versus partial bowel obstruction. The patient is comfortable, although the abdomen is still markedly distended and the nasogastric tube output is over 1 L per shift. The patient’s vital signs and lab results are all normal. What would you do?

See next issue for discussion.

Continued on page 21

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WARNING: LIMITATIONS OF USE, GASTROINTESTINAL, BLEEDING, CARDIOVASCULAR, and RENAL RISK Limitations of Use–SPRIX® (ketorolac tromethamine) Nasal Spray, a nonsteroidal anti-inflammatory drug (NSAID), is indicated for short-term (up to 5 days in adults) management of moderate to moderately severe pain that requires analgesia at the opioid level.

Do not exceed a total combined duration of use of SPRIX® and other ketorolac formulations (IM/IV or oral) of 5 days.

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IMPORTANT SAFETY INFORMATION WARNING: LIMITATIONS OF USE, GASTROINTESTINAL, BLEEDING, CARDIOVASCULAR, and RENAL RISK Limitations of Use–SPRIX® (ketorolac tromethamine) Nasal Spray, a nonsteroidal anti-inflammatory drug (NSAID), is indicated for short-term (up to 5 days in adults) management of moderate to moderately severe pain that requires analgesia at the opioid level. Do not exceed a total combined duration of use of SPRIX® and other ketorolac formulations (IM/IV or oral) of 5 days.

SPRIX® is not indicated for use in pediatric patients and it is not indicated for minor or chronic painful conditions.

Gastrointestinal Risk–Ketorolac tromethamine, including SPRIX®, can cause peptic ulcers, gastrointestinal bleeding and/ or perforation of the stomach or intestines, which can be fatal.

These events can occur at any time during use and without warning symptoms. Therefore, SPRIX ® is contraindicated in patients with active peptic ulcer disease, in patients with recent gastrointestinal bleeding or perforation, and in patients with a history of peptic ulcer disease or gastrointestinal bleeding. Elderly patients are at greater risk for serious gastrointestinal events.

Bleeding Risk–Ketorolac tromethamine inhibits platelet function and is, therefore, contraindicated in patients with suspected or confirmed cerebrovascular bleeding, patients with hemorrhagic diathesis, incomplete hemostasis and those at high risk of bleeding.

Cardiovascular Risk–NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk.

SPRIX® is contraindicated for treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.

Renal Risk–SPRIX® is contraindicated in patients with advanced renal impairment and in patients at risk for renal failure due to volume depletion.

SPRIX® is contraindicated in patients with known hypersensitivity or history of asthma, urticaria, or other allergic-type reactions to aspirin, ketorolac, other NSAIDs or EDTA. However, anaphylactoid reactions may occur in patients with or without a history of allergic reactions to aspirin or NSAIDs. SPRIX® is contraindicated in patients as a prophylactic analgesic prior to major surgery; or in labor, delivery, or nursing mothers because of the potential adverse effects of prostaglandin-inhibiting drugs on neonates.

SPRIX® should not be used concomitantly with IM/IV or oral ketorolac, aspirin, or other NSAIDs, or with probenecid or pentoxifylline. When ketorolac is administered with aspirin, its protein binding is reduced, although the clearance of free ketorolac is not altered. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of SPRIX® and aspirin is not generally recommended because of the potential of increased adverse effects.

Do not use SPRIX® in patients for whom hemostasis is critical.

Clinical studies, as well as postmarketing observations, have shown that ketorolac can reduce the natriuretic effect of furosemide and thiazides in some patients.

Concomitant use of ACE inhibitors and/or angiotensin II receptor antagonists may increase the risk of renal impairment, particularly in volume-depleted patients. NSAIDs may diminish the antihypertensive effect of ACE inhibitors and/or angiotensin II receptor antagonists.

Consider this interaction in patients taking SPRIX® concomitantly with ACE inhibitors and/or angiotensin II receptor antagonists.

Ketorolac can cause serious GI adverse events including bleeding, ulceration, and perforation. Elderly patients are at increased risk for serious GI events.

Use SPRIX® with caution in patients with impaired hepatic function or a history of liver disease.

The pharmacologic activity of SPRIX® in reducing inflammation and fever may diminish the utility of these diagnostic signs in detecting infections.

SPRIX® is a non-narcotic option for patients who require analgesia at the opioid level In a study of post-abdominal or -orthopedic surgery, SPRIX® provided signiĮcantly greater pain reducƟon vs placebo2 P=0.012 SPRIX®

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1.55 mg m or m maatc t hiing plaace cebo boo foollloow wiiing ng suurrggeeryy (da d y 0)). Al A l pa p titiennts t hadd accceesss ss to to morph orrpphhinne su sulf ulfat lffat a e (M MS) S) by pa patitien tien entt co cont ontro nttroolllledd ana nalg lgges esia es siaa (PCA (P CA)) be CA begi giinn nnin ingg on dayy 0. Th in T e sttud u y wa wass ddeessiignneedd wiitth a muulttiddosse regi reegiime m n of SPRIX PPR RIX IX® 311..5 mg mg or matc matc ma tchi tchi h ng ng pla lace ceeboo addm min inis isste tereed th thre ree titime time mess p r da pe dayy foor up to 5 daays ys.. B Baack ckup kupp ana nalg llgges esia iaa was per ermitt mitt mi tted teedd. TToottaal hy hyst stteerrecto ecto ec tomi miies m e weerre th the ma majoorir tyy of ab abdo bddoom miina nal suurgger ery pr proc oced oc eddurre (887% 7%). %). Hipp reepl plac acceem acem men entss wer eree th t e mo most st com mmo mon or orthhoped orth oppeddic pro roceedu duree (72 72%)). O Ottheer pprroc o eedduurres es werre ov ovaarria ian cy cyst steccto tomy omy my,, laam miinneeccttom my, y rot otaattoorr cufff rreepa pair airr, frac fr actu ac tuure redduc uctitit on andd fixat a ioon, saallpi ping n oo--ooph ooopphhoorreecctoomy my,, bbrrea east sstt rec econ onnst onst struct ruuccttioon, n, appppennde dect dect ctom oom my, y, anndd kne neee an and aannkklle reepl p acceem men e t.3 A ter Af teer suurg rger ery, er y int y, ntrraave v noouuss opi pioi oiid wa was aaddmi mini n st ster ereedd at thhe ddiiscre er ssccreettiion on of thhe innvveessttiggator aattorr. Pa Patitit eennts reeccor orde dedd pain de paainn int nten ensi en s ty (PI si PI)) raatit nggs us u ing inng a Vi Visu sual a al Anal An a ogg Scaale al l (VA V S) S) of 0 (n ( o pa pain iinn) to to 100 00 mm (w wor orst st pai a n) n). Wh Wheenn PI rraatiting ngs eq equa u leed at ua at lea east asstt 40 on the he VAS AS, paatitien ents en ts rec ecei eive ei vedd SP ve S RI R X® or pl p ac aceb ebo. o4 o.

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increased incidence of cardiovascular events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. Fluid retention, edema, retention of NaCl, oliguria, and elevations of serum urea nitrogen and creatinine have been reported in clinical trials with ketorolac. Only use SPRIX® very cautiously in patients with cardiac decompensation or similar conditions.

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Treat patients for the shortest duration possible, and do not exceed 5 days of therapy with SPRIX®.

Please see following pages for Brief Summary of Prescribing Information, including Boxed Warning.

References: 1. Boyer KC, McDonald P, Zoetis T. A novel formulation of ketorolac tromethamine for intranasal administration: preclinical safety evaluation. Int J Toxicol. 2010;29(5):467-478.

2. Levin RA. Clinical Review of NDA 22.382. FDA Center for Drug Evaluation and Research. October 5, 2009. 3. Brown C, Moodie J, Bisley E, Bynum L. Intranasal ketorolac for postoperative pain: a phase 3, double-blind, randomized study. Pain Med. 2009;10(6):1106-1114. 4. Singla N, Singla S, Minkowitz HS, Moodie J, Brown C. Intranasal ketorolac for acute postoperative pain.

Curr Med Res Opin. 2010;26(8):1915-1923.

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HIGHLIGHTS OF PRESCRIBING INFORMATION * * * *

WARNING: LIMITATIONS OF USE, GASTROINTESTINAL, BLEEDING, CARDIOVASCULAR, and RENAL RISK See first page for complete boxed warning • Limitations of Use – The total duration of use of SPRIX and other ketorolac formulations should not exceed 5 days.

• Gastrointestinal (GI) Risk – Ketorolac can cause peptic ulcers, GI bleeding, and/or perforation of the stomach or intestines, which can be fatal. SPRIX is CONTRAINDICATED in patients with peptic ulcer disease or history of GI bleeding.

• Bleeding Risk – SPRIX inhibits platelet function and is CONTRAINDICATED in patients with suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis, or high risk of bleeding.

• Cardiovascular (CV) Risk – NSAIDs may cause an increased risk of serious CV thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with CV disease or risk factors for CV disease may be at greater risk. SPRIX is CONTRAINDICATED for treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.

• Renal risk – SPRIX is CONTRAINDICATED in patients with advanced renal impairment and in patients at risk for renal failure due to volume depletion.

SPRIX is available as an intranasal spray product containing the active ingredient (ketorolac tromethamine) and the excipients edetate disodium (EDTA), monobasic potassium phosphate, sodium hydroxide, and water for injection. Each single-day nasal spray bottle contains a sufficient quantity of solution to deliver 8 sprays for a total of 126 mg of ketorolac tromethamine. Each spray delivers 15.75 mg of ketorolac tromethamine. ®

INDICATIONS AND USAGE SPRIXX® is indicated in adult patients for the short term (up to 5 days) management of moderate to moderately severe pain that requires analgesia at the opioid level. (1)*

• Serious and potentially fatal cardiovascular thrombotic events, myocardial infarction, and stroke can occur with NSAID treatment. (5.6)

resulted in renal papillary necrosis and other renal injury such as interstitial nephritis and nephrotic syndrome.

• Fluid retention and edema have been observed in patients taking NSAIDs. SPRIX® should be used with caution in patients with cardiac decompensation or similar conditions. (5.4, 5.6)

Anaphylactoid Reactions. As with other NSAIDs, anaphylactoid reactions may occur in patients with or without a history of allergic reactions to aspirin or NSAIDs and in patients without known prior exposure to ketorolac. SPRIXX® should not be given to patients with the aspirin triad.

• NSAIDs can cause serious dermatologic adverse reactions such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, which can be fatal. SPRIXX® should be discontinued immediately in patients with skin reactions. (4, 5.7) • During pregnancy, use of SPRIX® beyond 30 weeks gestation can cause premature closure of the ductus arteriosus, resulting in fetal harm. (5.8) ADVERSE REACTIONS The most common adverse reactions (incidence > 2%) in patients treated with SPRIXX® and occurring at a rate at least twice that of placebo are nasal discomfort, rhinalgia, increased lacrimation, throat irritation, oliguria, rash, bradycardia, decreased urine output, increased ALT and/or AST, hypertension, and rhinitis. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact American Regent, Inc. at 1-800-734-9236 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch DRUG INTERACTIONS • Concomitant use with anticoagulants may increase the risk of serious GI bleeding. (7.1) * * * * SEE ADDITIONAL INFORMATION BELOW AND FULL PRESCRIBING INFORMATION. Limitations of Use. The total duration of use of SPRIX® alone or sequentially with other formulations of ketorolac (IM/IV or oral) must not exceed 5 days because of the potential for increasing the frequency and severity of adverse reactions associated with the recommended doses. Treat patients for the shortest duration possible, and do not exceed 5 days of therapy with SPRIX®.

SPRIX® must not be used concomitantly with other forms of ketorolac or other NSAIDs. CONTRAINDICATIONS • Use in patients with active peptic ulcer disease, in patients with recent gastrointestinal bleeding or perforation, and in patients with a history of peptic ulcer disease or gastrointestinal bleeding

DOSAGE AND ADMINISTRATION

• Use in patients with a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs

• For adult patients < 65 years of age: 31.5 mg (one 15.75 mg spray in each nostril) every 6 to 8 hours. The maximum daily dose is 126 mg. (2.2)

• Use as a prophylactic analgesic before any major surgery

• For patients > 65 years of age, renally impaired patients, and patients less than 50 kg (110 lbs): 15.75 mg (one 15.75 mg spray in only one nostril) every 6 to 8 hours. The maximum daily dose is 63 mg. (2.3) • SPRIXX® has not been shown to be safe and effective in pediatric patients. (2.1) • SPRIX® nasal spray should be discarded within 24 hours of taking the first dose, even if the bottle still contains some medication. (2.4)

• Use during the perioperative period in the setting of coronary artery bypass graft (CABG) surgery. Use in patients with advanced renal disease or patients at risk for renal failure due to volume depletion • Use in labor and delivery. Through its prostaglandin synthesis inhibitory effect, ketorolac may adversely affect fetal circulation and inhibit uterine contractions, thus increasing the risk of uterine hemorrhage

DOSAGE FORM AND STRENGTHS

• Use in nursing mothers because of the potential adverse effects of prostaglandin-inhibiting drugs on neonates

Nasal spray: 15.75 mg of ketorolac tromethamine in each 100 μL spray.

Each 1.7 g bottle contains 8 sprays. (3)

• Use in patients a with suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis, or those for whom hemostasis is critical

CONTRAINDICATIONS • Known hypersensitivity to ketorolac, aspirin, other NSAIDs, or EDTA (4, 5.5, 5.7, 5.11)

• Known hypersensitivity to ketorolac tromethamine, aspirin, to other NSAIDs or ethylenediamine tetraacetic acid (EDTA) T

• Use in patients with active peptic ulcer disease, recent GI bleeding or perforation, or a history of peptic ulcers or GI bleeding (4, 5.2)

• Concomitant use with probenecid or pentoxifylline W WARNINGS AND PRECAUTIONS

• Use in patients with a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs (4, 5.5, 5.7, 5.11)

Gastrointestinal (GI) Effects - Risk of Ulceration, Bleeding, and Perforation

• Use as a prophylactic analgesic before any major surgery (4, 5.3) • Use during the perioperative period in the setting of coronary artery bypass graft (CABG) surgery (4, 5.6) • Use in patients with advanced renal disease or patients at risk for renal failure due to volume depletion (4, 5.4, 5.6) • Use in labor and delivery (4, 5.8) • Use in patients with suspected or confirmed cerebrovascular bleeding, patients with hemorrhagic diathesis, incomplete hemostasis, and those at high risk of bleeding (4, 5.3) W WARNINGS AND PRECAUTIONS • SPRIXX® should not be used concomitantly with IM/IV or oral ketorolac, aspirin, or other NSAIDs. (5.1) • Ketorolac can cause serious GI adverse events including bleeding, ulceration, and perforation. SPRIX® should be prescribed with caution in patients with a prior history of ulcer disease or GI bleeding. Elderly patients are at greater risk for serious GI events. (4, 5.2) • NSAIDs affect platelet aggregation and may cause bleeding complications.

SPRIX® should be used with caution in patients who have coagulation disorders or are on therapy that affects hemostasis. Do not use SPRIX® in patients for whom hemostasis is critical. (4, 5.3) • Ketorolac can cause renal injury. SPRIX® should not be used in patients with advanced renal disease or patients at risk for renal failure due to volume depletion, and should be used with caution in patients taking diuretics or ACE inhibitors. (4, 5.4, 12.4) • Anaphylactoid reactions may occur in patients with or without a history of allergic reactions to aspirin or NSAIDs. SPRIX® should be discontinued immediately in patients with allergic reactions. (4, 5.5, 5.7, 5.11) * Numbers refer to section of full prescribing information.

SPRIXX® is contraindicated in patients with previously documented peptic ulcers and/or GI bleeding. Ketorolac tromethamine can cause serious GI adverse events including bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. The incidence and severity of GI complications increases with increasing dose of, and duration of treatment with, ketorolac. In addition to past history of ulcer disease, other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients, and therefore, special care should be taken in treating this population. To T minimize the potential risk for an adverse GI event, the lowest effective dose should be used for the shortest possible duration. For high risk patients, consider alternate therapies that do not involve NSAIDs. Use great care when giving SPRIXX® to patients with a history of inflammatory bowel disease (ulcerative colitis, Crohn’s disease) as their condition may be exacerbated. a Hematological Effects. Use caution with use of ketorolac tromethamine in patients who have coagulation disorders, and monitor these patients carefully. Postoperative hematomas and other signs of wound bleeding have been reported in association with peri-operative use. Therefore, use SPRIX® with caution in the postoperative setting when hemostasis is critical. Do not use SPRIX® in patients for whom hemostasis is critical.

Renal Effects. Ketorolac and its metabolites are eliminated primarily by the kidneys. Patients with reduced creatinine clearance will have diminished clearance of the drug. SPRIX® is contraindicated in patients with advanced renal impairment. Patients treated with SPRIX® should be adequately hydrated. Use SPRIX® with caution in patients with impaired renal function, heart failure, liver dysfunction, those taking diuretics or ACE inhibitors, and the elderly. Long-term administration of NSAIDs has

Cardiovascular Effects • Cardiovascular (CV) Thrombotic Events Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious CV thrombotic events, myocardial infarction and stroke, which can be fatal.

Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible.

• Hypertension NSAIDs can lead to onset of new hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. • Congestive Heart Failure and Edema Fluid retention, edema, retention of NaCl, oliguria, and elevations of serum urea nitrogen and creatinine have been reported in clinical trials with ketorolac.

Therefore, only use SPRIX® very cautiously in patients with cardiac decompensation a or similar conditions.

Skin Reactions. NSAIDs, including ketorolac, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal.

These serious events may occur without warning. Inform patients about the signs and symptoms of serious skin manifestations, and discontinue use of the drug at the first appearance of skin rash or any other sign of hypersensitivity.

Pregnancy. Starting at 30 weeks gestation, SPRIX® can cause fetal harm when administered to a pregnant woman due to an increased risk of premature closure of the ductus arteriosus. If SPRIX® is used at or after 30 weeks gestation, the patient should be apprised of the potential hazard to a fetus.

Hepatic Effects. Use SPRIX® with caution in patients with impaired hepatic function or a history of liver disease. Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs, including ketorolac. In addition, rare cases of severe hepatic reactions, including jaundice, fulminant hepatitis, liver necrosis, and hepatic failure, some of them with fatal outcomes, have been reported.

Inflammation and Fever. The pharmacological activity of SPRIX® in reducing inflammation and fever may diminish the utility of these diagnostic signs in detecting infections.

Preexisting Asthma. Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, a do not administer SPRIXX® to patients with this form of aspirin sensitivity, and use with caution in patients with preexisting asthma.

Eye Exposure. Avoid contact of SPRIX® with the eyes. If eye irritation occurs, wash out eye with water or saline, and consult a physician if irritation persists for more than one hour.

ADVERSE REACTIONS The most frequently reported adverse reactions were related to local symptoms, i.e., nasal discomfort or irritation. These reactions were generally mild and transient in nature. The most common drug-related adverse events leading to premature discontinuation were nasal discomfort or nasal pain (rhinalgia).The data described below reflect exposure to SPRIXX® in patients enrolled in placebo-controlled efficacy studies of acute pain following major surgery. Most patients were receiving concomitant opioids, primarily PCA morphine.

Table 1. Post-operative Patients with Adverse Reactions Observed at a rate of 2% or more and at least twice the incidence of the placebo group.

SPRIX® (N=455) Placebo (N= 245) Nasal discomfort

15%

2%

Rhinalgia

13%

<1%

Lacrimation increased

5%

0%

Throat irritation

4%

<1%

Oliguria

3%

1%

Rash

3%

<1%

Bradycardia

2%

<1%

Urine output decreased

2%

<1%

ALT and/or AST increased

2%

1%

Hypertension

2%

1%

Rhinitis

2%

<1%

In controlled clinical trials in major surgery, primarily knee and hip replacements and abdominal hysterectomies, seven patients (N=455, 1.5%) treated with SPRIX® experienced serious adverse events of bleeding (4 patients) or hematoma (3 patients) at the operative site versus one patient (N=245, 0.4%) treated with placebo (hematoma). Six of the seven patients treated with SPRIX® underwent a surgical procedure and/or blood transfusion and the placebo patient subsequently required a blood transfusion.

DRUG INTERACTIONS Ketorolac is highly bound to human plasma protein (mean 99.2%). There is no evidence in animal or human studies that ketorolac induces or inhibits hepatic enzymes capable of metabolizing itself or other drugs.

GENERAL SuRGERY NEWS / FEBRuARY 2012

surgeons’ lounge 21

continued from page 16

Expertess Expr

you think laparoscopic Q.Docholecystectomy is an outpatient procedure?

Warfarin, Digoxin, Salicylate, and Heparin. Therapeutic concentrations of digoxin, warfarin, ibuprofen, naproxen, piroxicam, acetaminophen, phenytoin, and tolbutamide did not alter ketorolac protein binding.

michael sarr, mD: yes

Daniel Herron, mD: yes, if done early on a healthy patient

Aspirin. When ketorolac is administered with aspirin, its protein binding is reduced, although the clearance of free ketorolac is not altered. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of SPRIX® and aspirin is not generally recommended because of the potential of increased side effects.

Diuretics. Clinical studies, as well as postmarketing observations, have shown that ketorolac can reduce the natriuretic effect of furosemide and thiazides in some patients.

Jeffrey Ponsky, mD:

yes

Probenecid. Concomitant administration of oral ketorolac and probenecid resulted in decreased clearance and volume of distribution of ketorolac and significant increases in ketorolac plasma levels (total AUC increased approximately threefold from 5.4 to 17.8 mcg/h/mL), and terminal half-life increased approximately twofold from 6.6 to 15.1 hours. Therefore, concomitant use of SPRIX® and probenecid is contraindicated.

ronald Hinder, mD: yes r

Lithium. NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance.

The mean minimum lithium concentration increased 15%, and the renal clearance was decreased by approximately 20%. Thus, when SPRIX® and lithium are administered concurrently, observe patients carefully for signs of lithium toxicity.

Methotrexate. NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that they could enhance the toxicity of methotrexate. Use caution when SPRIXX® is adminitered concomitantly with methotrexate.

edward Felix, mD: of course, if it’s elective but in some acute patients, hospitalization is required

ed Phillips, mD: yes, for some patients alejandro Gandsas, mD: yes

ACE Inhibitors/Angiotensin II Receptor Antagonists. Concomitant use of ACE inhibitors and/or angiotensin II receptor antagonists may increase the risk of renal impairment, particularly in volume-depleted patients. Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE inhibitors and/or angiotensin II receptor antagonists. Consider this interaction in patients taking SPRIX® concomitantly with ACE inhibitors and/or angiotensin II receptor antagonists.

anthony Petrick, mD: yes a

Antiepileptic Drugs. Sporadic cases of seizures have been reported during concomitant use of ketorolac and antiepileptic drugs (phenytoin, carbamazepine).

michael schweitzer, mD: yes, for some patients

Psychoactive Drugs. Hallucinations have been reported when ketorolac was used in patients taking psychoactive drugs (fluoxetine, thiothixene, alprazolam).

Pentoxifylline. When ketorolac is administered concurrently with pentoxifylline, there is an increased tendency to bleeding. Therefore, concomitant use of SPRIX® and Pentoxifylline is contraindicated.

natan Zundel, mD: yes, in 10% to 12% of the time

lee swanstrom, mD:

yes

Nondepolarizing Muscle Relaxants. In postmarketing experience there have been reports of a possible interaction between ketorolac and nondepolarizing muscle relaxants that resulted in apnea.

Selective Serotonin Reuptake Inhibitors (SSRIs). There is an increased risk of gastrointestinal bleeding when selective serotonin reuptake inhibitors (SSRIs) are combined with NSAIDs. Fluticasone/Oxymetazoline. The rate and extent of absorption of ketorolac from SPRIX® administration were assessed in subjects with allergic rhinitis before and after the administration of a single daily dose of fluticasone and oxymetazoline. There was no effect on the pharmacokinetic characteristics of SPRIX® that can be considered clinically significant.

maher abbas, mD: yes

alfons Pomp, mD: yes, in about half of my patients

DRUG ABUSE AND DEPENDENCE Ketorolac does not bind to opiate receptors.

Symptoms and Signs. Symptoms following acute NSAID overdose are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care.

Gastrointestinal bleeding can occur.r Hypertension, acute renal failure, respiratory depression, and coma may occur, but are rare.

Treatment. Manage patients using symptomatic and supportive care following an NSAID overdose. There are no specific antidotes.

estuardo Behrens, mD: yes

ed lin, mD: yes

Frederick Greene, mD: no

emanuelle lo menzo, mD: no

PATIENT COUNSELING INFORMATION Instruct patients to read the NSAID Medication Guide that accompanies each prescription dispensed.

Bruce ramshaw, mD: usually

David edelman, mD: no, I prefer 23-hour overnight stay

ashutosh Kaul, mD: most

of the time BS8880A Revised 7/2011

Distributed by: American Regent, Inc. Shirley, NY 11967

raul rosenthal, mD:

no

22

in the news

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

Surgical Education: Finally, There Are Some Apps for That ‘there are many social networks but this one is for surgery residents to connect purely on an educational level. we aim to facilitate education and the exchange of ideas.’

b y V ictoria S terN

I

n 2009, Dale Dangleben, MD, FACS, got his first iPhone. After perusing the iPhone’s functions and available applications, he realized that very few surgical education tools existed in the app store.

“Smartphone apps are designed to be easy to use, quick to load and high yield. They can be created, edited and revised very quickly compared with traditional textbooks. So, I began the journey to create really functional apps for the students of surgery,” said Dr. Dangleben, associate residency program director in the Department of Surgery at Lehigh Valley Health Network, Allentown, Penn.

Dr. Dangleben and his colleague James Lee, MD, created several free surgical education apps for iPhones and iPads to give surgeons the tools to practice their skills at any time without having to carry around cumbersome surgical textbooks. The free tools include an app for surgeons to practice taking the ABSITE; apps that present radiographic, trauma, minimally invasive and lower endoscopy scenarios; and an app that provides the American Association for the Surgery of Trauma organ injury scale (visit http://surgeryresidentnetwork.ning.com for more details).

The pair also founded the Surgery Resident Network, a free educational service.

Within the group, surgery residents can share content with their peers. They can start a discussion in the forum, launch a blog, take a quiz, share lectures and more.

Additionally, the site does not allow patient information.

“There are many social networks but this one is for surgery residents to connect purely on an educational level,” Dr. Dangleben explained. “We aim to facilitate

—Dale Dangleben, MD, FACS education and the exchange of ideas.”

Dr. Dangleben credits his residents, especially Dr. Lee; Firas Madbak, MD; Ryan Lawless MD; and Ramon Garza, MD, for being instrumental in helping implement these ideas.

inside the apps Figure 1. a radiographic app allows users to view a variety of scenarios specific to a topic.

Figure 2. the trauma app allows surgeons to view real cases and apply their knowledge.

axillary

continued from page 1 breast tumors that were 5 cm or smaller as well as minimal sentinel node (SN) involvement, defined as one or more micrometastatic (≤2 mm) SNs. Patients were not included if they had pure ductal carcinoma in situ, previous systemic therapy for breast cancer, chemoprevention within the past year, distant metastases, palpable axillary lymph nodes and a previous or concomitant malignancy.

Patients were randomized to either receive ALND or not to receive ALND. The arms were well balanced in terms of tumor size, tumor grade, tumor histology, estrogen and progesterone receptor status and local and systemic treatment.

At SABCS, the researchers discussed outcomes of

Surgical residents can study and practice their skills using the ABSITE quiz app, which provides a thorough review of general surgery questions. Each question comes with a full explanation and added references for further reading.

The radiographic, trauma, minimally invasive and lower endoscopy apps allow users to view a variety of scenarios specific to each topic. The apps provide a range of images or scenarios and the user has to find the pathology or diagnose the patient. Each app also comes with multiple-choice questions or a quiz related to the image or scenario. The trauma app, for instance, allows surgeons to view real cases and apply their knowledge to manage the patient (Figures 1 and 2).

“The surgical apps not only present everyday cases but also [provide] challenging clinical diagnoses,” said Dr. Dangleben. “They allow the surgeon to develop a fundamental knowledge of surgery and identify and answer relevant questions related to certain diseases.”

931 patients. With a median folBoth IBCSG 23-01 and ACOSOG ‘i hope everyone will Z-11 met less than half of their tarlow-up of 57 months, no difference was identified between the go home and stop doing geted accrual goals, reflecting the diftwo arms in the primary end point ficulties in conducting a trial that axillary dissections on challenges conventional practice; howof disease-free survival (88.4%, no ALND vs. 87.3%, ALND; hazard women with clinically ever, the results demonstrate the value ratio, 0.87; 80% confidence interof such trials. negative nodes and a val, 0.67-1.12; below noninferi“I hope everyone will go home ority boundary of 1.25; P=0.48) positive sentinel node.’ and stop doing axillary dissections on and for the secondary end point women with clinically negative nodes —Laura Esserman, MD and a positive sentinel node,” said of overall survival (98.0%, no ALND vs. 97.6%; P=0.35).

Laura Esserman, MD, professor in the As expected, adverse events were more frequent in Departments of Surgery and Radiology and affiliate patients in the ALND arm than in the non-ALND faculty at the Institute for Health Policy Studies, and group, including sensory neuropathy (18% vs. 12%), director of the Carol Franc Buck Breast Care Center, lymphedema (13% vs. 4%) and motor neuropathy (8% University of California, San Francisco. “More is not vs. 3%). better—that is what the data show.”

12 to 14 times more effective

maximised absorption

early enteral feeding Speed Patient Recovery with Moss Tubes Feeding patients immediately after surgery has been proven to accelerate healing and shorten hospital stays. The best way to adminster post-operative feeding is with Moss Gastrostomy Tubes.

Their patented design permits delivery of nourishment directly to the distal duodenum while providing 12 to 14 times more effective decompression than conventional gastric suction devices.

In short, Moss Tubes help patients maximise nutritional absorption, experience greater comfort, and enjoy a quicker return to health.

For more information, call (800) 827-0470 or fax (518) 674-8067 Moss Tubes, Inc. P.O. Box 378, West Sand Lake, NY 12196-0378

www.mosstubesinc.com

24

in the news

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

Surgeons Address Gastric Band Slips in Post-Pars Flaccida Era Two Approaches Focus on Prevention and Staged Repair b y g abriel m iller San antonio—Following the success and widespread adoption of the pars flaccida technique in gastric banding, surgeons are now turning their attention to preventing and managing the small percentage of patients who still

prolapse, particularly in the anterior stomach.

Two studies addressed the issue: One aimed to show the effectiveness of preventing band slips with sutures and a second suggested that a staged repair may help the most serious prolapsed patients.

To prevent slips, several suturing techniques are based on the idea that fixing the stomach more firmly in place prevents the movement that causes bands

to slip. Suturing techniques are now relatively common in practice, even though there is no firm data to support it.

“I place additional plication sutures in the fundus below the band when I think there is a lot of floppy stomach because I feel like it may help and it doesn’t add too much to the surgery,” said Jaime Ponce, MD, a bariatric surgeon at Dalton Surgical Group in Dalton, Ga., and president-elect of the American Society for Metabolic and Bariatric Surgery.

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“There is no real science, but in our mind we feel that it is helping.”

The suturing study, originally presented at the annual meeting of the Society of Gastrointestinal and Endoscopic Surgeons, was conducted by one of the most experienced gastric banding groups in the country at New York University in New York City. In the study, Jonathan Zagzag, MD, retrospectively compared the gastric band slippage rate between two of the four surgeons in the group from July 2007 to May 2010 (Surg Endosc 2011 Sep 23. [Epub ahead of print]). One surgeon used an additional plication suture below the band in every patient (n=589), the other never used an additional suturing technique (n=776). Revision was the main outcome. Both surgeons performed a hiatal hernia repair in more than 70% of patients at the time of band placement.

Dr. Zagzag described the suturing technique in the study as “basically three sutures right below the band, with three bites—one at the greater curvature, one in the middle of the stomach and one at the lesser curvature—to hopefully decrease the laxity of the stomach.”

Overall, both surgeons had very low revision rates. Among the patients who did not receive the additional plication sutures, only 0.26% required revision compared with 1.5% of patients in the suture group. The difference was not statistically significant (P<0.09).

The results demonstrate one of the problems of studying gastric band prolapse in the post-pars flaccida era: Although it is one of the most common complications, the rates are already so low that a study would require a very large number of patients to find a statistically significant difference in slip rates.

“It’s tough to go against 0.26%,” said Dr. Zagzag. “Unfortunately, we didn’t see a statistical difference but we did see a very low rate [in the suture group] compared with the accepted average.”

Although retrospective study cannot settle the question, it provides early data and suggests that a prospective study might be warranted, particularly because the suture group had a relatively low rate of band slippage.

“This retrospective study has less scientific validity because there were two different surgeons doing two different techniques,” said Dr. Ponce, “but the importance is that it’s the first time that there’s been a comparison.”

The second study examined the efficacy

in the news 25

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

’there is no CPt [Current Procedural terminology] code for unbuckling the band and then coming back and repositioning it. ... i think a lot of insurers may not pay for it.’

—Jaime Ponce, MD of a two-stage revision procedure for patients with the most serious gastric band prolapses (Surg Endosc 2011 [Epub ahead of print]). The technique—which requires unbuckling the band, reducing the slipped tissue and later returning for definitive revision— is not groundbreaking, but the study provides important data on the viability of the procedure for the patients who have severe inflammation at the site of the band.

The research also presents an option for general surgeons in rural areas who see gastric band patients with emergent food intolerance or dysphagia.

“It’s a viable option, but not necessarily the first line of treatment,” said lead author Sebastian Eid, MD, a bariatric surgeon at Hackensack University Medical Center (HUMC) in Hackensack, N.J. “Also, this may be the preferred treatment for non-bariatric surgeons, especially at rural hospitals, who see patients with bands. After this treatment, they can refer the patient to a bariatric surgeon for revision at a later date.”

Of the 1,548 patients who received gastric bands between January 2006 and August 2010 at HUMC, 12 underwent a staged repair for band slippage, with one patient lost to follow-up due to medical illness. The mean time to slip diagnosis was 28.45 months, at which point patients’ mean body mass index (BMI) dropped from 45 to 27 kg/m2.

The average “wait time” between slip diagnosis and final revision was 15.7 weeks, during which time patients’ BMI climbed back to 33 kg/m2, a 22% increase between the first “unbuckling” stage and the second definitive revision.

After final revision, patients’ BMI remained constant at three-, six- and 12-month measurements.

Two of the bands were ultimately explanted at patients’ request because of nausea and discomfort, although Dr. Eid said that esophogram and intraoperative evaluation showed the bands to be in an appropriate position.

Originally, Dr. Eid said the investigators planned to bring patients back for revision within six weeks of slip diagnosis, but reimbursement and payment issues delayed the final revision in several cases.

“We are usually able to get them back, but I think that may be part of why the time in between the first and second stages was so long—trying to get the insurance [companies]s to approve it,” Dr. Eid said.

The problem is a significant one and it’s not likely to resolve any time soon; a one-stage revision has a relatively

low complication rate, but even getting approval for the one-stage standard band revision can be time-consuming and difficult.

“It is going to get a little bit tricky with the insurance,” said Dr. Ponce.

“There is no CPT [current procedural terminology] code for unbuckling the band and then coming back and repositioning it. ... I think a lot of insurers may not pay for it.”

Nevertheless, for the most extreme cases, Dr. Ponce agreed that it might be medically necessary. “I wouldn’t call it a routine way to approach slippages,” he

said. “But if you see that the stomach is very nasty—a lot of tissue damage from the slippage or strangulation of the tissue, or it’s edematous—if you try to do something when [the stomach] is damaged that’s when problems arise, so clinical judgment is important to decide when it’s appropriate to stage it.”

Disclosures: Drs. Eid and Zagzag reported no relevant financial relationships or commercial interests to disclose. Dr. Ponce reported previously receiving honoraria or other consulting fees from Allergan and Ethicon Endo-Surgery.

More effective than iodine-based products at eliminating skin microorganisms.

Period.

ChloraPrep® products have been shown to outperform iodine-based products.1,2 The evidence is in. When it comes to eliminating bacteria from the skin, there is a difference. ChloraPrep® skin antiseptic is becoming a new standard of care for preoperative skin antisepsis.

“Chlorhexidine gluconate is superior to povidoneiodine for preoperative antisepsis for the patient and surgeon.” 3

References: 1. Saltzman MD, Nuber GW, Gryzlo SM, Marecek GS, Koh JL. Efficacy of surgical preparation solutions in shoulder surgery. J Bone Joint Surg Am. 2009;91(8):1949–1953. 2. Ostrander RV, Botte MJ, Brage ME. Efficacy of surgical preparation solutions in foot and ankle surgery. J Bone Joint Surg Am. 2005;87(5):980–985. 3. Fletcher N, Sofianos DM, Berkes MB, Obremskey WT. Prevention of perioperative infection. J Bone Joint Surg Am. 2007;89(7):1605–1618.

carefusion.com/chloraprep | 800.523.0502

© 2012 CareFusion Corporation or one of its subsidiaries. All rights reserved.

CHLORAPREP is a registered trademark of CareFusion Corporation or one of its subsidiaries. ADV-Period1211

26

on the spot

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

with Colleen Hutchinson

”the art of Herniology” introduction

As we did in the January 2012 issue of General Surgery News, this month we focus on “the art of herniology.” We have another round of hernia meetings coming up, and their high annual attendance reflects the need for guidance, education and maybe even consensus in this area of general surgery. But there are still many options within the realm of hernia care

that surgeons do not agree on, and we explore those areas of debate in the Gut Reaction Table below and in the roundtable discussion of the treatment of sportsman’s hernia on page 27. As long as hernia repair remains the most common procedure performed by surgeons in the united States, this should be required reading.

—Colleen Hutchinson — Colleen Hutchinson is a communications consultant who specializes in the areas of general surgery and bariatrics. She can be reached at colleen@cmhadvisors.com.

Gut Reaction: Hernia (continued from January 2012, page 24) Contributor

association membership and attendee Fees

Centers of excellence

annual meetings = education

industry-driven science

Karl LeBlanc, MD

Too high, choices are not necessary

Unnecessary; the cream will rise to the top.

In most cases, yes

Unproven mesh technologies looking for validation

Michael Rosen, MD

Going to become a problem

Too soon for hernias

Sometimes

Unfortunate fact of life

William Richards, MD

Out of control

Instrumental in reducing operative mortality and creating data regarding the outcomes of bariatric surgery that go beyond the case series so prevalent in the past

For most, the annual meetings are key CME events

Some are very valuable, whereas others are pure marketing

Dmitry Oleynikov, MD

Who says there is no inflation?

No!

Only if you show up!

Follow the money

Alfons Pomp, MD

Necessary evil (Advamed)

Inevitable as outcomes are assessed

Not always in the lecture halls

NOTES, robotics, single incision

B. Todd Heniford, MD

Pick those that continue to educate and inspire me

Each hospital should be a center where excellence is achieved

Yes

Important, but stagnant and copycat of late

Parviz Amid/David Chen, MD

You get what you pay for.

Absolutely

Good annual meetings

A necessity, but be well informed and impartial

Michael Sarr, MD

Appropriate, needed

Great idea need better audits of data

Good idea but depends on the surgeon

The future—need collaborative efforts

Aurora Pryor, MD

Part of my practice

Should focus on quality

Yes! Also networking and innovating

Unfortunate truth to capitalism

Colleen Hutchinson

The intersection of bureaucracy and inflation or of innovation and learning?

Dr. LeBlanc: The cream will rise to the top

Let’s check back in a year.

Dr. Pories: It’s been way overmaligned. Participation of the industry is essential for progress.

Dr. Gagner: Each individual is an industry.

Dr. Schauer: True science is agnostic to the funder.

on the spot 27

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

Sportsman’s Hernia: A panel of experts was asked whether they recommend rest or surgery for the treatment of sportsman’s hernia, based on their own clinical expertise. Here are the responses. surgeon Panelist

recommend rest/reach for the scalpel

Adrian Park, MD

Recommend rest. Following a thorough history and physical examination—nothing new or earth-shattering here, but particularly important in this situation—my initial plan of action is actually inaction … for the patient. Rest usually is accompanied by a trial of NSAIDs [nonsteroidal anti-inflammatory drugs] and often the services of an expert physical therapist. Also key is patient education to refrain from exercising or playing again until he or she starts to feel better (because the patient can be potentially at a lower threshold for reinjury otherwise). It is not that I see no role for surgery, but the literature offers little guidance at this point. If I do operate for a “sports hernia,” it’s because I have identified a clear lesion to be addressed.

Michael Sarr, MD

For mildly symptomatic patients, a trial of physical therapy and physiotherapy is appropriate for a sportsman’s hernia. However, when they don’t respond, an operative approach is indicated. Whether this is a placement of a prosthetic material in the preperitoneal area or whether it is a more complicated release of the appropriate involved tendons is debatable. The literature is not definitive on this topic.

Sometimes, the need for intervention in sportsman’s hernias is indicated by the inability of these patients to do what they want to do.

In this case, if there is no response to physiotherapy or physical therapy, an operative approach probably is indicated.

B. Todd Heniford, MD

Rest and medical treatment first, surgery second. As many surgeons can attest, the topic of sportsman’s hernias has become a true phenomenon. The surgical technique, although significantly varied by authors in the literature, appears to be straightforward. The diagnosis, preoperative treatment and the possible timing of surgery, however, are not as well delineated. My progression in therapy involves a team approach and always starts by having the patient seen by a true sports medicine physician. Typically, treatment commences with having the patient rest from the activity in question, medication, and physical therapy. Surgery is the fallback if this fails.

Michael Franz, MD

Reach for the scalpel. You don’t go from an intact inguinal canal to a mature hernia overnight. There is an obvious continuum. Clearly, athletic individuals are most likely to be symptomatic and to benefit from surgical therapy. I agree with the large European experience, and now others, that at operation occult defects in the posterior fascia of the inguinal canal are found.

A skilled and dedicated ultrasonographer can help select these patients preoperatively with dynamic studies. Finally, operations like the Munich repair are safe, and do not require mesh.

Aurora Pryor, MD

Recommend rest. There are data that support good outcomes from repair, but I question if the repair just leads to forced rehabilitation. I have seen patients do well with just a committed approach to rest and eventually physical therapy.

Michael Rosen, MD

Recommend rest. I do not entirely believe in the entity of sportsman’s hernia, and if you are not dealing with a professional-level athlete (i.e., soccer or hockey player), you need to put the knife down, find a great physical therapist and stay out of the groin.

our Health Care system lacks

our surgical unit has most need For

our most underrated staff member is

my mentor

Cms Classification of Bariatric wound infections as never-events

open surgery is

Consideration for the providers of care

A systems-based approach

Operative crew

Arthur Gilbert, MD

Ridiculous!

The preferred approach in the appropriate setting

A leader or a goal

Improved efficiency

A great intern

Jeff Ponsky, MD

What a joke!

Something we still need to teach

Incentives for providing costeffective care

More operating rooms

Scrub nurses

Has been instrumental in many aspects of my career

A ridiculous bureaucratic invention that Always going to be with us defies the laws of nature

Common sense

Time

The fellow

Too many to mention; learn from everyone

They are crazy; what’s new?

A necessary evil

Access for all

More ancillary staff (to care for patients), fewer administrators with lab coats and Blackberrys

Staff (floor) nurse

Wish I would have had one; have had great partners instead

More bureaucratic idiocy

Still sometimes necessary

Enough databases and people to track every patient outcome

More OR time

Scrub tech and statistician

My father, Hiram Polk, Dr. Ponsky, Mike Henderson; inspirational

Impossible; I live on a place called Earth

Often required

Efficiency

Consistency

The residents

Dr. Amid: Irving Lichtenstein, MD; Dr. Chen: Dr. Amid

Wishful thinking

A hernia waiting to happen

Insight, teeth, leadership and it needs to be out of Congress’ hands

Good administrative leadership

Pediatrician

Taught me lots

This is ridiculous, especially with redo open surgery

Still needed, and I am worried about who will do it in the future

Money

More staff

My scrub tech/nurse

I have several. That way it’s less work for each of them!

Wishful thinking on their part

Still needed for some cases

This box is not big enough.

I'm with Dr. Pomp on this one.

All great answers

My parents

This is like hitting an open wound, no pun intended.

As Dr. Richards says, “Always going to be with us….” As long as there are surgeons who know how to do it.

28

in the news

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

Preliminary Study: Patients Prefer Single-Incision Chole Despite Higher Wound Complication Rate; Surgeons Divided Over Study b y g abriel m iller San antonio—Single-incision cholecystectomy comes with a higher risk for wound complications as well as slightly more pain compared with traditional, four-port laparoscopy, according to an

ongoing study (Surg Endosc 2011 Nov 15. [Epub ahead of print]).

Despite the slightly better performance of traditional laparoscopy, patients said they clearly preferred the more cosmetic outcome of the single-incision approach.

The results, originally presented at the 2011 annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), demonstrate that single-incision cholecystectomy

“was technically feasible with no increase in biliary injury,” said lead author Melissa Phillips, MD, assistant professor of surgery at the University of Tennessee in Knoxville.

Dr. Phillips and her colleagues randomized 200 patients at 10 sites to receive standard four-port laparoscopic cholecystectomy or a single 20-mm umbilical incision using the SILS Port manufactured by Covidien. Patients with acute cholecystitis were excluded from

29th Annual

the study, as were patients with a history of umbilical hernia and those with a body mass index (BMI) greater than 45 kg/m2. Despite randomization, patients in the standard laparoscopic group had a statistically significant higher BMI of 31 kg/m2 compared with 28.9 kg/m2 in the single-incision group.

Because the results presented were preliminary, only 28% of all patients had met the planned one-year follow-up period.

'i want everyone to take this paper and recognize that this is data that tells you [that] you do not have to jump on the single-port bandwagon.'

—Carl Voyles, MD

al Special surgic ions oncology sess d Friday Thursday an afternoon.

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Visit us online for more information and registration: MiamiBreast2012.CancerLearning.com Course Director

Surgical Topics Include:

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• Axillary management in breast cancer—the next step toward individualized cancer care • Ablative therapy for benign lesions and small breast cancers • Management of common benign problems— case-based panel discussion • Surgical technique in intra-operative radiotherapy • Nipple-sparing mastectomy • Mammoplastic techniques in oncologic surgery • Partial breast reconstruction with pedicled perforated flap • Contralateral prophylactic mastectomy: pros and cons • Prophylactic mastectomy and autologous breast reconstruction • Managing breast cancer in patients with breast implants • Implant reconstruction in the irradiated breast • Management of central breast tumors • Acellular tissue matrices in breast reconstruction • Radiotherapy and autologous breast reconstruction • Surgical treatment of lymphedema

Co-Chairs Patrick I. Borgen, MD Robert DerHagopian, MD J. Michael Dixon, MD Debu Tripathy, MD

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Intraoperatively, the single-incision approach added an additional 12 minutes to the procedure (four-port, 45.2 minutes vs. single-incision, 57.2 minutes; P<0.0001), however, blood loss was nearly identical. Overall, there were no major differences in complications between the two surgical approaches.

“The total number of adverse events between the two groups were equal,” said Dr. Phillips; however, “when you start to look at the subcategories of these adverse events, you find some interesting differences.”

The most significant difference was found with wound complications.

Although none were severe, wound complications were four times more common in the single-incision arm (four-port, 2.5% vs. single-incision, 10.3%; P=0.047).

“It’s important to mention, however, that none of these wound complications required opening the incision or admission for IV antibiotics,” Dr. Phillips added.

Pain scores also were very similar, but at a few time points, “worst pain” and “average pain” scores were statistically higher in the single-incision group. At no point were the differences in pain scores greater than 1 on a 10-point scale, which has minimal, if any, clinical impact, Dr. Phillips said. Analgesic use postoperatively, for example, was equivalent between the groups.

One striking difference, the investigators noted, was patients’ preference for the single-incision operation. At all time points measured, patients preferred a single-incision over the four-port operation, as measured using a self-reported cosmesis scale and a photo questionnaire in which patients ranked their own scars against a series of other patients’ scars.

in the news 29

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

Quality-of-life measurements were less clear. At two time points, day 3 and week 2, single-incision patients reported higher quality-of-life scores, the explanation for which “is still a little unclear,” Dr. Phillips said.

Dr. Phillips emphasized, however, that the results are intermediate and cannot be extrapolated to patients with acute cholecystitis. Moreover, the results reflect the work of experienced surgeons, all of

whom had performed at least 10 pervious single-incision operations before enrolling patients.

The early results left surgeons divided: Advocates said it confirmed that the safety and feasibility thresholds for single-incision cholecystectomy had been met, whereas detractors said it meant that surgeons should not be in any rush to abandon traditional laparoscopy.

Driven by heavy marketing from

device manufacturers and a relatively manageable learning curve, single-incision techniques are becoming increasingly popular, a trend that’s reflected in the number of single-incision studies presented at SAGES. However, even among surgeons already performing the operation, there is no clear consensus that a single incision is better.

“I want everyone to take this paper and recognize that this is data that tells you [that] you do not have to jump on the single-port bandwagon,” said Carl Voyles, MD, clinical associate professor of surgery at the University of Mississippi Medical Center in Jackson. Dr. Voyles said he recently audited his last 150 patients with standard four-port technique and found much shorter operating room times and times to discharge compared with single-port techniques.

However, perhaps the biggest question regarding single-incision surgery— the one that may ultimately define the operation’s future—is the umbilical hernia rate that eventually comes out with longer follow-up.

The umbilical port is the most susceptible to late hernia and the incidence will certainly be increased with single-incision cases over time, Dr. Voyles said. “And one umbilical hernia blows

cosmesis to pieces,” he added.

In fact, some see the trial as essentially a hernia study comparing incision sizes. “[They’re] really comparing two types of umbilical incisions, one that may be as small as 3 to 7 mm versus a larger one for your multiport and it will be interesting to see how these patients do in the future and how many of them have umbilical complications or hernias,” said Andrew Morfesis, MD, private practice surgeon at Owen Drive Surgical Clinic in Fayetteville, N.C. One factor that could potentially affect the umbilical hernia rates in the four-port group is the extraction site for the gallbladder, which was not accounted for in the preliminary study, Dr. Phillips said.

Dr. Phillips said she hopes to have a multivariate analysis of the study for presentation at the American College of Surgeons annual Clinical Congress in October.

The study was sponsored by Covidien. Dr. Phillips reported she has received contracted research support from Covidien. Drs. Morfesis and Voyles reported no financial ties or other relationships with any manufacturer or provider of commercial products or services relevant to this study.

30

in the news

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

In Large Colectomy Study, Open Approach Seen as Harmful Selection Bias a Major Limitation of the Data b y g abriel m iller

O

laparoscopic group (odds ratio [OR], 4.87; P<0.001).

The investigators then conducted a regression analysis to correct for patient comorbidities as well as a logistic regression, which accounted for ASA class, preoperative functional status, wound class and emergency cases.

With these factors accounted for, the OR with open colectomy remained greater than 1.5 for each of the individual ICU-level complications measured and was 1.74 for a Clavien Grade IV or V complication. The OR for mortality was 1.54 for an open procedure.

“This is a spectacular use of the NSQIP database,” said Jo Buyske, MD, associate executive director of

Bilimoria, MD, MS, assistant professor of surgery at the Northwestern Feinberg School of Medicine in Chicago, who has published more than a dozen papers on NSQIP patients.

“The authors have done their best to risk adjust for the two patient populations, but there is no opportunity to understand or adjust for selection bias,” said Heidi Nelson, MD, professor of surgery at Mayo Clinic in Rochester, Minn., and co-chair of the American College of Surgeons Oncology Group. “The bottom line is we know that practices are not equivalent and patients are not equivalent, and the selection that goes on is complex and exceeds an ability to adjust for it.”

The question, then, is how to interpret the entire body of data on laparoscopic versus open colectomy.

“The big randomized trials didn’t show major differences in complications,” said Dr. Nelson, who led the landmark COST trial published in 2004, which found similar recurrence and survival rates among patients prospectively randomized to either open or laparoscopic colectomy (N Engl J Med 2004;350:2050-2059). “[Laparoscopy] wasn’t safer—but it was as safe.”

Gregory Kennedy, MD, PhD, assistant professor of surgery at the University of Wisconsin in Madison, added, “If we’re sticking to good data from randomized controlled trials, we cannot support the stance that laparoscopy provides improved short-term outcomes.”

However, even though the NSQIP study likely had significant selection bias, “with 12,000 patients in one arm and 33,000 in another, it’s such a big group that it can’t all be biased, there have got to be some differences and there is probably some truth to what they are saying,” Dr. Kennedy said. “Furthermore, every paper that has been published has found the same thing from retrospective databases.

So there has got to be some truth to it, but are these data enough to say that laparoscopy can be the gold standard?” he added. “Unfortunately, probably not.”

For a more thorough discussion of laparoscopic colectomy and the barriers to wider adoption, see the September issue of General Surgery News (“Lap Colectomy Rates Still Low, Despite Strong Outcomes,” 2011;38:9).

Disclosures: Drs. Bilimoria, Kennedy, Nelson and Webb all reported no relevant financial relationships or significant commercial interests. Dr. Buyske reported she is an employee of the American Board of Surgery and that has an ownership interest in Sunstones Biotech.

So Mr. Forde rewired some switches and slipped green sleeves over just four bulbs (as opposed to 42 under “white” conditions). Under these conditions, the average light reading was 86 lux, just 5% of that under white lights.

At first glance, the green light “looks weird,” Dr. Goldman admitted. “Initially a lot of people didn’t like it. I didn’t like it. It made me feel just a little off balance. But I and everyone else got used to it quickly.”

Mr. Forde said eyes adjust quickly to the green, and in three to five minutes “you feel as if you have stepped into a bright room again.”

The internal surgical site is unaffected because it is still illuminated under white light. No glare or screen washout was seen. Anesthesiologists were able to read labels and plunger lines without walking over to a reading light and potentially tripping en route. They could also better assess the patient to see whether his or her head or limbs moved. Flashlights are still kept handy, however, Dr. Goldman said.

The success of the trial has led MGH to expand the green lights to 28 ORs. “Once you go green,” Dr. Goldman said, “it’s hard to go back.”

pen colectomy is an independent risk factor for intensive care unit (ICU)-level complications and death when compared with laparoscopic colectomy, according to a recently published study in Surgical Endoscopy (2011 Oct 25. [Epub ahead of print]).

The study, which was originally presented at the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) meeting, not only adds to a growing body of literature suggesting that laparoscopic colectomy is safer ’the big randomized trials didn’t show major than open colectomy over the shortterm, but also extends that implica- differences in complications. laparoscopy wasn’t tion to the most serious ICU-level safer—but it was as safe.’ complications.

Many previous studies compar- Heidi Nelson, MD ing the safety of laparoscopic versus open colectomy have focused on short-term end points like length of stay, whereas larger randomized trials like the COST (Clinical Outcomes of Surgical Therapy) study and the UK MRC CLASICC (United Kingdom Medical Research Council Conventional versus Laparoscopic-Assisted Surgery in Colorectal Cancer) trial have been powered primarily for oncologic outcomes, such as tumor recurrence or resection success.

In the current study, which is a risk-adjusted analysis of some 45,000 colectomy patients, Shawn Webb, MD, colon and rectal surgeon at Henry Ford Health System in Detroit, and colleagues reviewed all laparoscopic and open colectomies in the American College of Surgeons National Surgical Quality Initiative Plan (NSQIP) database from 2005 to 2008. NSQIP data are prospectively collected and observational: Assigning patients to either the laparoscopic or open group is done at the discretion of the operating surgeon.

The investigators screened patients specifically for Clavien Grade IV and V complications, such as single-organ dysfunction requiring dialysis or a ventila- the American Board of Surgery and past president of tor, which are considered life threatening. During the SAGES. “People complain about the expense and difthree-year study period, 12,455 patients underwent lap- ficulty of it, but [this study] shows its power.” aroscopic colectomy, compared with 33,190 who had an But because the study is based on observational open procedure. Patients in the open group had a worse data, and colectomy patients vary widely, selection bias American Society of Anesthesiologists (ASA) classifi- is a major limitation. cation score prior to surgery.

“Basically, no matter what kind of adjustment you When the data were unadjusted for preoperative do, you can’t adjust completely, and there are too patient characteristics, 15.4% of patients in the open many differences and reasons that people choose to group had a complication, compared with 3.5% in the have surgery open versus laparoscopically,” said Karl

green light

Continued from page 9 it was 3.44 lux. (A typical living room, by contrast, is about 50 lux, Dr. Goldman said.) Ryan Forde, an engineer at MGH who assisted in the project, said most ORs have two or three switches and no dimmers, probably because of limitations with the ballast.

Monitors have improved dramatically over the years to cut the glare, but more was needed. The human eye is most sensitive to the color green, said Dr. Goldman.

TYGACIL is in the IDSA/SIS guidelines for cIAI and the SIS guidelines for cSSSI.1,2

Expanded broad-spectrum coverage * is on your side

*TYGACIL does not cover Pseudomonas aeruginosa.

TYGACIL is indicated for the treatment of adults with: s Complicated skin and skin structure infections caused by Escherichia coli, Enterococcus faecalis (vancomycin-susceptible isolates), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus agalactiae, Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Streptococcus pyogenes, Enterobacter cloacae, Klebsiella pneumoniae, and Bacteroides fragilis s Complicated intra-abdominal infections caused by Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Enterococcus faecalis (vancomycin-susceptible isolates), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Clostridium perfringens, and Peptostreptococcus micros s Community-acquired bacterial pneumonia caused by Streptococcus pneumoniae (penicillin-susceptible isolates), including cases with concurrent bacteremia, Haemophilus influenzae (beta-lactamase negative isolates), and Legionella pneumophila

Important Safety Information s 49'!#), IS CONTRAINDICATED IN PATIENTS WITH KNOWN HYPERSENSITIVITY TO TIGECYCLINE s !NAPHYLAXIS ANAPHYLACTOID REACTIONS HAVE BEEN REPORTED WITH NEARLY ALL ANTIBACTERIAL AGENTS INCLUDING TIGECYCLINE AND MAY BE LIFE THREATENING 49'!#), SHOULD BE ADMINISTERED WITH CAUTION IN PATIENTS WITH KNOWN HYPERSENSITIVITY TO TETRACYCLINE CLASS ANTIBIOTICS s )SOLATED CASES OF SIGNIlCANT HEPATIC DYSFUNCTION AND HEPATIC FAILURE HAVE BEEN REPORTED IN PATIENTS BEING TREATED WITH TIGECYCLINE 3OME OF THESE PATIENTS WERE RECEIVING MULTIPLE CONCOMITANT MEDICATIONS 0ATIENTS WHO DEVELOP ABNORMAL LIVER FUNCTION TESTS DURING TIGECYCLINE THERAPY SHOULD BE MONITORED FOR EVIDENCE OF WORSENING HEPATIC FUNCTION !DVERSE EVENTS MAY OCCUR AFTER THE DRUG HAS BEEN DISCONTINUED s 4HE SAFETY AND EFlCACY OF 49'!#), IN PATIENTS WITH HOSPITAL ACQUIRED PNEUMONIA HAVE NOT BEEN ESTABLISHED s An increase in all-cause mortality has been observed across phase 3 and 4 clinical studies in TYGACIL-treated patients versus comparator-treated patients. The cause of this increase has not been established. This increase in all-cause mortality should be considered when selecting among treatment options s TYGACIL may cause fetal harm when administered to a pregnant woman s The use of TYGACIL during tooth development may cause permanent discoloration of the teeth. 49'!#), SHOULD NOT BE USED DURING TOOTH DEVELOPMENT UNLESS OTHER DRUGS ARE NOT LIKELY TO BE EFFECTIVE OR ARE CONTRAINDICATED s !CUTE PANCREATITIS INCLUDING FATAL CASES HAS OCCURRED IN ASSOCIATION WITH TIGECYCLINE TREATMENT #ONSIDERATION SHOULD BE GIVEN TO THE CESSATION OF THE TREATMENT WITH TIGECYCLINE IN CASES SUSPECTED OF HAVING DEVELOPED PANCREATITIS s Clostridium difficile ASSOCIATED DIARRHEA #$!$ HAS BEEN REPORTED WITH USE OF NEARLY ALL ANTIBACTERIAL AGENTS INCLUDING 49'!#), AND MAY RANGE IN SEVERITY FROM MILD DIARRHEA TO FATAL COLITIS s -ONOTHERAPY SHOULD BE USED WITH CAUTION IN PATIENTS WITH CLINICALLY APPARENT INTESTINAL PERFORATION s 49'!#), IS STRUCTURALLY SIMILAR TO TETRACYCLINE CLASS ANTIBIOTICS AND MAY HAVE SIMILAR ADVERSE EFFECTS 3UCH EFFECTS MAY INCLUDE PHOTOSENSITIVITY PSEUDOTUMOR cerebri, and anti-anabolic action (which has led to increased BUN, azotemia, acidosis, and hyperphosphatemia). As with tetracyclines, pancreatitis has been REPORTED WITH THE USE OF 49'!#), s 4O REDUCE THE DEVELOPMENT OF DRUG RESISTANT BACTERIA AND MAINTAIN THE EFFECTIVENESS OF 49'!#), AND OTHER ANTIBACTERIAL DRUGS 49'!#), SHOULD BE USED ONLY TO TREAT INFECTIONS PROVEN OR STRONGLY SUSPECTED TO BE CAUSED BY SUSCEPTIBLE BACTERIA !S WITH OTHER ANTIBACTERIAL DRUGS USE OF 49'!#), MAY RESULT IN OVERGROWTH OF NON SUSCEPTIBLE ORGANISMS INCLUDING FUNGI s 4HE MOST COMMON ADVERSE REACTIONS INCIDENCE ARE NAUSEA VOMITING DIARRHEA INFECTION HEADACHE AND ABDOMINAL PAIN s 0ROTHROMBIN TIME OR OTHER SUITABLE ANTICOAGULANT TEST SHOULD BE MONITORED IF 49'!#), IS ADMINISTERED WITH WARFARIN s #ONCURRENT USE OF ANTIBACTERIAL DRUGS WITH ORAL CONTRACEPTIVES MAY RENDER ORAL CONTRACEPTIVES LESS EFFECTIVE s 4HE SAFETY AND EFFECTIVENESS OF 49'!#), IN PATIENTS BELOW AGE AND LACTATING WOMEN HAVE NOT BEEN ESTABLISHED Please see brief summary of Prescribing Information on adjacent page.

References: 1. 3OLOMKIN *3 -AZUSKI *% "RADLEY *3 ET AL $IAGNOSIS AND MANAGEMENT OF COMPLICATED INTRA ABDOMINAL INFECTION IN ADULTS AND CHILDREN GUIDELINES BY THE 3URGICAL )NFECTION 3OCIETY AND THE )NFECTIOUS $ISEASES 3OCIETY OF !MERICA Clin Infect Dis 2. -AY !+ 3TAFFORD 2% "ULGER %- ET AL 3URGICAL )NFECTION 3OCIETY 'UIDELINES 4REATMENT OF COMPLICATED SKIN AND SOFT TISSUE INFECTIONS Surg Infect 3. 49'!#),® TIGECYCLINE 0RESCRIBING )NFORMATION Wyeth Pharmaceuticals Inc. TYG281206-01 © 2011 Pfizer Inc. All rights reserved. Printed in USA/April 2011

32

a TYGACIL® (tigecycline) Brief Summary Vancomycin/Aztreonam, Imipenem/Cilastatin, Levofloxacin, Linezolid. b See package insert for full Prescribing Information. For further product information and current package insert, please LFT abnormalities in TYGACIL-treated patients were reported more frequently in the post therapy period than those visit www.wyeth.com or call our medical communications department toll-free at 1-800-934-5556. in comparator-treated patients, which occurred more often on therapy.

INDICATIONS AND USAGE In all Phase 3 and 4 studies that included a comparator, death occurred in 4.0% (150/3788) of patients receiving TYGACIL is indicated for the treatment of adults with complicated skin and skin structure infections caused by TYGACIL and 3.0% (110/3646) of patients receiving comparator drugs. An increase in all-cause mortality has been Escherichia coli, Enterococcus faecalis (vancomycin-susceptible isolates), Staphylococcus aureus (methicillinobserved across phase 3 and 4 clinical studies in TYGACIL treated patients versus comparator. The cause of susceptible and -resistant isolates), Streptococcus agalactiae, Streptococcus anginosus grp. (includes S. anginosus, this increase has not been established. This increase should be considered when selecting among treatment S. intermedius, and S. constellatus), Streptococcus pyogenes, Enterobacter cloacae, Klebsiella pneumoniae, and options. (See Table 2.)

Bacteroides fragilis.

Table 2. Patients with Outcome of Death by Infection Type TYGACIL is indicated for the treatment of adults with complicated intra-abdominal infections caused by Citrobacter TYGACIL Comparator Risk Difference* freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Enterococcus faecalis Infection Type n/N % n/N % % (95% CI) (vancomycin-susceptible isolates), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Bacteroides fragilis, cSSSI 12/834 1.4 6/813 0.7 0.7 (-0.3, 1.7) Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Clostridium perfringens, and cIAI 42/1382 3.0 31/1393 2.2 0.8 (-0.4, 2.0) Peptostreptococcus micros.

CAP 12/424 2.8 11/422 2.6 0.2 (-2.0, 2.4) TYGACIL is indicated for the treatment of adults with community-acquired pneumonia infections caused HAP 66/467 14.1 57/467 12.2 1.9 (-2.4, 6.3) a

by Streptococcus pneumoniae (penicillin-susceptible isolates), including cases with concurrent bacteremia, 41/336 12.2 42/345 12.2 0.0 (-4.9, 4.9) Non-VAP Haemophilus influenzae (beta-lactamase negative isolates), and Legionella pneumophila.

25/131 19.1 15/122 12.3 6.8 (-2.1, 15.7) VAPa CONTRAINDICATIONS RP 11/128 8.6 2/43 4.7 3.9 (-4.0, 11.9) TYGACIL is contraindicated for use in patients who have known hypersensitivity to tigecycline.

DFI 7/553 1.3 3/508 0.6 0.7 (-0.5, 1.8) WARNINGS AND PRECAUTIONS Overall Adjusted 150/3788 4.0 110/3646 3.0 0.6 (0.1, 1.2)** Anaphylaxis/Anaphylactoid Reactions CAP = Community-acquired pneumonia; cIAI = Complicated intra-abdominal infections; cSSSI = Complicated skin and Anaphylaxis/anaphylactoid reactions have been reported with nearly all antibacterial agents, including skin structure infections; HAP = Hospital-acquired pneumonia; VAP = Ventilator-associated pneumonia; RP = Resistant TYGACIL, and may be life-threatening. TYGACIL is structurally similar to tetracycline-class antibiotics and pathogens; DFI = Diabetic foot infections. should be administered with caution in patients with known hypersensitivity to tetracycline-class antibiotics. * The difference between the percentage of patients who died in TYGACIL and comparator treatment groups. The 95% Hepatic Effects CI for each infection type was calculated using the normal approximation method without continuity correction.

Increases in total bilirubin concentration, prothrombin time and transaminases have been seen in patients treated ** Overall adjusted (random effects model by trial weight) risk difference estimate and 95% CI. with tigecycline. Isolated cases of significant hepatic dysfunction and hepatic failure have been reported in patients a These are subgroups of the HAP population. being treated with tigecycline. Some of these patients were receiving multiple concomitant medications. Patients who develop abnormal liver function tests during tigecycline therapy should be monitored for evidence of worsening Note: The studies include 300, 305, 900 (cSSSI), 301, 306, 315, 316, 400 (cIAI), 308 and 313 (CAP), 311 (HAP), 307 hepatic function and evaluated for risk/benefit of continuing tigecycline therapy. Adverse events may occur after the [Resistant gram-positive pathogen study in patients with MRSA or Vancomycin-Resistant Enterococcus (VRE)], and 319 (DFI with and without osteomyelitis). drug has been discontinued.

In comparative clinical studies, infection-related serious adverse events were more frequently reported for subjects Mortality Imbalance and Lower Cure Rates in Ventilator-Associated Pneumonia treated with TYGACIL (7%) versus comparators (6%). Serious adverse events of sepsis/septic shock were more A study of patients with hospital acquired pneumonia failed to demonstrate the efficacy of TYGACIL. In this study, patients were randomized to receive TYGACIL (100 mg initially, then 50 mg every 12 hours) or a comparator. In addition, frequently reported for subjects treated with TYGACIL (2%) versus comparators (1%). Due to baseline differences between treatment groups in this subset of patients, the relationship of this outcome to treatment cannot be patients were allowed to receive specified adjunctive therapies. The sub-group of patients with ventilator-associated pneumonia who received TYGACIL had lower cure rates (47.9% versus 70.1% for the clinically evaluable population) established [see WARNINGS AND PRECAUTIONS].

The most common treatment-emergent adverse reactions were nausea and vomiting which generally occurred during and greater mortality (25/131 [19.1%] versus 14/122 [11.5%]) than the comparator. the first 1 – 2 days of therapy. The majority of cases of nausea and vomiting associated with TYGACIL and comparators Use During Pregnancy were either mild or moderate in severity. In patients treated with TYGACIL, nausea incidence was 26% (17% mild, 8% TYGACIL may cause fetal harm when administered to a pregnant woman. If the patient becomes pregnant while taking tigecycline, the patient should be apprised of the potential hazard to the fetus. Results of animal studies moderate, 1% severe) and vomiting incidence was 18% (11% mild, 6% moderate, 1% severe). indicate that tigecycline crosses the placenta and is found in fetal tissues. Decreased fetal weights in rats and rabbits In patients treated for complicated skin and skin structure infections (cSSSI), nausea incidence was 35% for TYGACIL and 9% for vancomycin/aztreonam; vomiting incidence was 20% for TYGACIL and 4% for vancomycin/aztreonam. In (with associated delays in ossification) and fetal loss in rabbits have been observed with tigecycline [see USE IN patients treated for complicated intra-abdominal infections (cIAI), nausea incidence was 25% for TYGACIL and 21% SPECIFIC POPULATIONS]. for imipenem/cilastatin; vomiting incidence was 20% for TYGACIL and 15% for imipenem/cilastatin. In patients treated Tooth Development for community-acquired bacterial pneumonia (CABP), nausea incidence was 24% for TYGACIL and 8% for levofloxacin; The use of TYGACIL during tooth development (last half of pregnancy, infancy, and childhood to the age of vomiting incidence was 16% for TYGACIL and 6% for levofloxacin.

8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). Results of studies in rats with Discontinuation from tigecycline was most frequently associated with nausea (1%) and vomiting (1%).

TYGACIL have shown bone discoloration. TYGACIL should not be used during tooth development unless other drugs For comparators, discontinuation was most frequently associated with nausea (<1%). are not likely to be effective or are contraindicated.

The following adverse reactions were reported infrequently (<2%) in patients receiving TYGACIL in clinical studies: Clostridium difficile-Associated Diarrhea Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Body as a Whole: injection site inflammation, injection site pain, injection site reaction, septic shock, allergic reaction, chills, injection site edema, injection site phlebitis TYGACIL, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the Cardiovascular System: thrombophlebitis normal flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these Digestive System: anorexia, jaundice, abnormal stools infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients Metabolic/Nutritional System: increased creatinine, hypocalcemia, hypoglycemia who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported Special Senses: taste perversion to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing Hemic and Lymphatic System: partial thromboplastin time (aPTT), prolonged prothrombin time (PT), eosinophilia, antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte increased international normalized ratio (INR), thrombocytopenia management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted Skin and Appendages: pruritus as clinically indicated.

Urogenital System: vaginal moniliasis, vaginitis, leukorrhea Patients With Intestinal Perforation Post-Marketing Experience Caution should be exercised when considering TYGACIL monotherapy in patients with complicated intra-abdominal The following adverse reactions have been identified during postapproval use of TYGACIL. Because these reactions infections (cIAI) secondary to clinically apparent intestinal perforation. In cIAI studies (n=1642), 6 patients treated with are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their TYGACIL and 2 patients treated with imipenem/cilastatin presented with intestinal perforations and developed sepsis/ frequency or establish causal relationship to drug exposure. Anaphylaxis/anaphylactoid reactions, acute pancreatitis, septic shock. The 6 patients treated with TYGACIL had higher APACHE II scores (median = 13) versus the 2 patients hepatic cholestasis, jaundice, and severe skin reactions, including Stevens-Johnson Syndrome. treated with imipenem/cilastatin (APACHE II scores = 4 and 6). Due to differences in baseline APACHE II scores between DRUG INTERACTIONS treatment groups and small overall numbers, the relationship of this outcome to treatment cannot be established.

Warfarin Tetracycline-Class Effects Prothrombin time or other suitable anticoagulation test should be monitored if tigecycline is administered with warfarin TYGACIL is structurally similar to tetracycline-class antibiotics and may have similar adverse effects. Such effects may include: photosensitivity, pseudotumor cerebri, and anti-anabolic action (which has led to increased BUN, azotemia, [see CLINICAL PHARMACOLOGY (12.3) in full Prescribing Information].

Oral Contraceptives acidosis, and hyperphosphatemia). As with tetracyclines, pancreatitis has been reported with the use of TYGACIL. Concurrent use of antibacterial drugs with oral contraceptives may render oral contraceptives less effective.

Superinfection As with other antibacterial drugs, use of TYGACIL may result in overgrowth of non-susceptible organisms, including fungi. USE IN SPECIFIC POPULATIONS Pregnancy Patients should be carefully monitored during therapy. If superinfection occurs, appropriate measures should be taken.

Teratogenic Effects—Pregnancy Category D [see WARNINGS AND PRECAUTIONS] Development of Drug-Resistant Bacteria 14 Prescribing TYGACIL in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit Tigecycline was not teratogenic in the rat or rabbit. In preclinical safety studies, C-labeled tigecycline crossed the placenta and was found in fetal tissues, including fetal bony structures. The administration of tigecycline was to the patient and increases the risk of the development of drug-resistant bacteria. associated with slight reductions in fetal weights and an increased incidence of minor skeletal anomalies (delays ADVERSE REACTIONS Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical in bone ossification) at exposures of 5 times and 1 times the human daily dose based on AUC in rats and rabbits, trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates respectively (28 mcg·hr/mL and 6 mcg·hr/mL at 12 and 4 mg/kg/day). An increased incidence of fetal loss was observed at maternotoxic doses in the rabbits with exposure equivalent to human dose. observed in practice.

There are no adequate and well-controlled studies of tigecycline in pregnant women. TYGACIL should be used during In clinical trials, 2514 patients were treated with TYGACIL. TYGACIL was discontinued due to adverse reactions in pregnancy only if the potential benefit justifies the potential risk to the fetus.

7% of patients compared to 6% for all comparators. Table 1 shows the incidence of treatment-emergent adverse Nursing Mothers reactions through test of cure reported in 2% of patients in these trials.

Results from animal studies using 14C-labeled tigecycline indicate that tigecycline is excreted readily via the milk of Table 1. Incidence (%) of Adverse Reactions Through Test of Cure lactating rats. Consistent with the limited oral bioavailability of tigecycline, there is little or no systemic exposure to Reported in 2% of Patients Treated in Clinical Studies tigecycline in nursing pups as a result of exposure via maternal milk.

Body System TYGACIL Comparatorsa It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution Adverse Reactions (N=2514) (N=2307) should be exercised when TYGACIL is administered to a nursing woman [see WARNINGS AND PRECAUTIONS].

Body as a Whole Pediatric Use Abdominal pain 6 4 Safety and effectiveness in pediatric patients below the age of 18 years have not been established. Because of effects Abscess 2 2 on tooth development, use in patients under 8 years of age is not recommended [see WARNINGS AND PRECAUTIONS].

Asthenia 3 2 Geriatric Use Headache 6 7 Of the total number of subjects who received TYGACIL in Phase 3 clinical studies (n=2514), 664 were 65 and over, Infection 7 5 while 288 were 75 and over. No unexpected overall differences in safety or effectiveness were observed between Cardiovascular System these subjects and younger subjects, but greater sensitivity to adverse events of some older individuals cannot be Phlebitis 3 4 ruled out.

Digestive System No significant difference in tigecycline exposure was observed between healthy elderly subjects and younger subjects Diarrhea 12 11 following a single 100 mg dose of tigecycline [see CLINICAL PHARMACOLOGY (12.3) in full Prescribing Information].

Dyspepsia 2 2 Hepatic Impairment Nausea 26 13 Vomiting 18 9 No dosage adjustment is warranted in patients with mild to moderate hepatic impairment (Child Pugh A and Child Hemic and Lymphatic System Pugh B). In patients with severe hepatic impairment (Child Pugh C), the initial dose of tigecycline should be 100 mg Anemia 5 6 followed by a reduced maintenance dose of 25 mg every 12 hours. Patients with severe hepatic impairment (Child Metabolic and Nutritional Pugh C) should be treated with caution and monitored for treatment response [see CLINICAL PHARMACOLOGY (12.3) Alkaline Phosphatase Increased 3 3 and DOSAGE AND ADMINISTRATION (2.2) in full Prescribing Information].

Amylase Increased 3 2 OVERDOSAGE Bilirubinemia 2 1 No specific information is available on the treatment of overdosage with tigecycline. Intravenous administration of BUN Increased 3 1 TYGACIL at a single dose of 300 mg over 60 minutes in healthy volunteers resulted in an increased incidence of Healing Abnormal 3 2 nausea and vomiting. In single-dose intravenous toxicity studies conducted with tigecycline in mice, the estimated Hyponatremia 2 1 median lethal dose (LD50) was 124 mg/kg in males and 98 mg/kg in females. In rats, the estimated LD50 was Hypoproteinemia 5 3 106 mg/kg for both sexes. Tigecycline is not removed in significant quantities by hemodialysis. b 4 5 SGOT Increased This Brief Summary is based on TYGACIL direction circular LAB-0458-2.0, revised 01/11. b SGPT Increased 5 5 Respiratory System Pneumonia 2 2 Nervous System Dizziness 3 3 Skin and Appendages Rash 3 4 TYG279434 © 2011 Pfizer Inc. All rights reserved. Printed in USA/February 2011

FEBRuARY 2012

The New England Journal at 200 b y g eorge o choa

T

he New England Journal of Medicine is turning 200 years old. From humble beginnings—the first issue in 1812 was distributed on horseback— NEJM now, in the words of its own Jan. 5, 2012 editorial, is “considered to be one of the premier journals in the field” (366:83).

The Jan. 5, 2012 issue includes a historical overview of NEJM (366:17), featuring such highlights as the first demonstration of surgical anesthesia in 1846, and early clinical descriptions of AIDS.

’we purposefully edit the journal so physicians from all specialties can find something of interest.’

—Jeffery Drazon, MD Allan M. Brandt, PhD, a historian of medicine at Harvard Medical School, in Boston, and author of the overview, said in an interview that NEJM “has a long history of publishing cuttingedge science in a wide area of medical domains. At the same time, however, it has also published major articles in broad areas of health policy, medical ethics, and public health that draw together a diverse constituency of readers.”

NEJM editor-in-chief Jeffrey Drazen, MD, said the journal has 10 editors— nine physicians and one geneticist— ”who spend a large amount of time seeking out and editing the best medical research in the world. Any research manuscript submitted for consideration as an original article or special article is reviewed and edited by at least five experts before it is published.” Dr. Drazen told General Surgery News, “We purposefully edit the journal so physicians from all specialties can find something of interest.”

To mark its 200th anniversary, NEJM is publishing anniversaryrelated articles throughout the year. It also has launched an anniversary Web site (http://nejm200.nejm.org) with an interactive historical timeline, plans to release a documentary and will host a symposium at Harvard Medical School.

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36

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GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

Milling Around b y P eter K im , mD

M

eetings have become the bane of a surgeon’s existence, mostly because we don’t get much out of them. I do, however, look forward to the opportunity to meet people I want to talk to, usually before or after the meeting, while I’m on my way to throw out my coffee cup. Or better yet, while I’m waiting for the elevator, a medicine attending might spot me and tell me about a patient, often dying in the medical intensive care unit (MICU), and how the medicine team has not been able to reach the surgery resident for a consult for two days. Then I say exactly what they want to hear, “Let’s go see the patient together, now.”

i am savoring this human activity now because i am aware of the ’nighthawk’ system, which will soon become the ’Dayhawk’ system.

In the era of “IT,” or instant technology, everything is fast and powerful, but like instant coffee, you get what you pay for. True, things are fast and the images on picture archiving and communication systems (PACS) are available at your fingertips; I see doctors yelling and hitting the screen when they can’t download a computed tomography (CT) scan within seconds. My job as a junior resident in the last decade of the 20th century was to collect all the films during the week and bring them to the operating rooms for the attending surgeons.

My favorite teaching times were when we met with specialists and I could learn something new. On certain services we would meet with the radiologists at a certain time every day and review films. Once a month, we would go to pathology and review slides on interesting cases. I must confess that these were the experiences as a resident that now give me the greatest pleasure as an attending. I visit my radiologists and talk about films for patients on whom I will operate, and usually they are happy to see a human being and hear additional clinical history, but they never turn on the lights.

The pathologists have nice paintings hanging in their hallways, bright lights and also are happy to see a human being

and hear some additional clinical history. The clinical history of “abdominal pain” entered on the computer requisition, which by the way is all the history that is known by the keypuncher, just doesn’t cut it.

So, radiologists make surgical diagnoses, and now they dictate care because— are you sitting down?—physicians who have not looked at the CT images themselves are now making clinical decisions.

Surgery consults are called after the images

are read, and some are radiologist. I am savoring Hang on to your performed when no one human activity now surgery caps, folks, this has looked at the images because I am aware of except an on-call postbecause surgery is the “Nighthawk” system, graduate year-2 radiolowill soon become now being outsourced which gy resident. Having been the “Dayhawk” system. burned—no, singed to a My highly paid radiology as well. crisp—by these earnest colleagues tell me there but misguided efforts, are no jobs any more. The my first stop on the way to the emer- recent medical student and radiology resgency room is usually the reading room idency graduates are in for a Big Bang where I can review the images with the because technology is no longer their

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friend. For the same reason that digital images allow radiology and surgical subspecialty attendings to no longer have to be in-house on-call like Level 1 trauma attendings, digital technology also allows images to be read by someone in Australia, Asia or Austria. U.S. board-certified radiologists can read a CT scan at 3 a.m., for less money, with more accuracy, and they will even talk to you on the phone or Skype if you have a question. Radiology now can be outsourced to save the system a few bucks. Hence, there will be no radiology reading jobs in America in 10 years.

Hang on to your surgery caps, folks,

because surgery is now being outsourced as well. On a recent trip to Costa Rica, I learned that insurance companies will pay for patients to receive certain procedures in foreign countries because these countries provide services that are cheaper, maybe better and tack on a postoperative medical spa service with a tour of the countryside for patients who can ambulate. The success of this business justifies from every perspective what is now called medical tourism. The activity of turismo de medicina has received one of the highest priorities for commerce from the Costa Rican government, and for

elective procedures covered by the Blues, the Reds, or the Blacks, why wouldn’t a savvy administrator support a less-expensive, elective procedure that saves everyone money? “Just Do It,” says the poster hanging next to the administrator’s MBA of health administration diploma.

So, as a general surgeon I mill around the hospital before and after meetings. I visit the emergency room first when I’m on-call to see what is happening before they call me. I take my frozen sections to pathology myself and watch them cut the tissue. I like talking to my consulting physicians face to face in the MICU.

Hitting “accept” on the computer screen, and sometimes even yelling into a cell phone, just doesn’t provide the same level of satisfaction. Like the great rooftop bars in Los Angeles, Las Vegas and Manhattan, part of the dying pleasures of medicine includes seeing and being seen.

—Dr. Kim is assistant professor of surgery, Albert Einstein College of Medicine, New York City.

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Continued from page 1 pass along the added expense to their customers. Many of these technologies need only be available in a single center in a local catchment area, but the rules of competition dictate that everyone who wants to be competitive must offer all of them. The result is to duplicate unnecessary equipment, which is purchased and now requires use. As the expression goes, “when you have a hammer, everything starts to look like a nail.”

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

Potential health care consumers are constantly barraged with advertising hype about the best hospitals in the area, which usually highlight their advanced technologies that start with catchy words such as robotic, laser, or cyber. When is the last time you heard an advertisement on television or the radio claiming that a medical center provides the least expensive or most appropriate care in the area?

This sales approach is in sharp contrast to other industries that always advertise the lowest price for automobiles, computers, airfares, or any product or service they are selling. Consequently, the cost

when is the last time you heard an advertisement on television or the radio claiming that a medical center provides the least expensive or most appropriate care in the area? of medical care is higher in communities where there is a lot of competition between providers than in communities

that have little to no competition. This surprising finding runs contrary to longheld theories of capitalism, which postulate that competition should drive down the prices of services.

This aberration in health care economics can be explained by the medical arms race, which is more intensely practiced in medically competitive communities. Hospitals or medical centers that are not competing for their share of the market have a lower need to provide boutique services or unneeded cutting-edge technology to attract patients. They can apply themselves to providing the most cost-effective and appropriate care.

The medical arms race, which is as wrong-headed and financially destructive as its nuclear forerunner, is one reason that we find ourselves in the difficult financial situation we face today. There are other reasons, however, including a dysfunctional tort system, a failure to audit and control Medicare and Medicaid expenditures and an inability to control expenditures for futile care, especially in the terminal stages of life. All of these are difficult problems, but they can be fixed.

Another popular concept from the Cold War era, the “Nash Equilibrium,” is useful to consider in this context. This game theory concept, first suggested by John Forbes Nash, holds that in most standoffs neither side gains by changing its behavior unilaterally, and therefore nobody changes. During the Cold War, neither the United States nor the Soviet Union would disarm unilaterally because each country feared that the loss of equilibrium would be at its own expense.

You might compare this standoff to situations occurring in medicine today. A huge increase in diagnostic studies is one problem that contributes to our rapidly increasing medical expenses. Doctors cannot be cost-conscious in their use of diagnostics because of the medical-legal consequences of not ordering the most sophisticated, and usually most expensive, diagnostic procedures. This situation should be addressed by appropriate tort reform. Lawyers, however, will not allow changes in the medical-legal system, which has been very profitable for them. Neither side will act unilaterally.

Another example is the sustainable growth rate (SGR) formula, which was developed to curb unsustainable inflation. Physicians, noting that their income will decrease with the application of the SGR formula, have been successful in temporarily blocking it for years and are trying to get it repealed. Lawmakers who see the tremendous inflation in medical expenses do not want to abandon the SGR formula, which they see as the best way to rein in expenses. Every two to six months, the issue is painfully revisited to the detriment of both parties involved.

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GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

the cost of medical care is higher in communities where there is a lot of competition between providers than in communities that have little to no competition.

The eventual thawing of the Cold War was achieved by a progressive deescalation of the irrational arms buildups through a series of acts such as the Nuclear Test Ban Treaty (1963), the Nuclear Non-Proliferation Treaty (1970), the Helsinki Accords (1975), the Strategic Arms Limitation Treaties I and II (1972 and 1979) and the Strategic Arms Reduction Treaties I and II (1991 and 1993). This negotiated drawdown led to restructuring (perestroika) and openness (glasnost) in the Soviet Union, which culminated in opening that country’s borders to the West.

On the other side of the world, things have changed as well. The North American Aerospace Defense Command (NORAD), the American–Canadian entity, which was built to detect and respond to intercontinental ballistic missiles, has been retooled in a swords-toplowshares strategy. According to its Web site, the organization is now tracking mainly domestic flights. Recently, one of the highest-level alerts was for a small Cessna that had flown too close to the U.S. Capitol building.

The field of medicine needs the same kind of negotiated disarmament. First, physicians and lawyers have to discuss tort reform. Doctors should accept that malpractice does exist and sometimes the victims should be compensated. On the other hand, judgments should be reviewed and adjudicated by experts.

In the case that payment is appropriate, it should go to the victim. The lawyers should not be the main beneficiaries of the system but should work on an hourly basis and not for a percentage of the award. They should not work on contingency, and frivolous suits should be

discouraged by appropriate penalties.

Additionally, there should be regulations to limit unnecessary diagnostics.

For example, the U.S. Preventive Services Task Force (part of the Department of Health and Human Services) has studied and advises against screening colonoscopies after 75 years of age, for prostate cancer after 75, and for cervical cancer after 65. In all these cases the risks outweigh the benefits, yet Medicare and Medicaid pay for all procedures even when the recipients are outside of these recommended age limits.

Medicare and Medicaid also pay for implantable cardiac defibrillators, cardiac stents and certain vertebral procedures

(such as vertebroplasty and kyphoplasty) for patients to whom these procedures provide no benefit and are sometimes harmful. In fact, it has been estimated that Medicare spends from 15% to 30% of its budget on contraindicated procedures, which translates roughly into $75 billion to $150 billion annually (nytimes. com/2011/05/26/opinion).

Patients and their doctors insist on these procedures and the purchasers of health insurance and the taxpayers are saddled with the bill. End-of-life decisions also are a political hot potato that nobody wants to handle. A significant portion of our health care resources is poured into the last days or weeks of life, often when it is known that the efforts are futile. All these issues call for a negotiated de-escalation and should be on the table.

In each situation described, there are some people who want to continue business as usual and to receive every kind of medical device, advanced technology, diagnostic procedure or end-of-life measure that is available, despite evidence that it will not be helpful. I think this is fine: People should be allowed to make choices about what treatment they wish to receive, but if the efficacy of the treatment they demand is not supported by clinical evidence, [then] they should

purchase it at their own expense. The medical insurance industry (and their customers) or the taxpayers should not be obligated to pay for ineffective, futile or harmful care.

Taking on these very emotional issues will require the political will and courage of our profession, the legal industry and lawmakers. In the 1960s, when our country was brought to the brink by the Cuban Missile crisis, the need for negotiation became clear. I think we are on the brink again, this time with health care financing; and it is time again for us to roll up our sleeves and start on the road to détente.

When I was in school in the 1950s and 1960s, we practiced what to do in case of a nuclear war. We were taught to crouch under our desks, put our heads between our legs and so forth. Some enterprising families in our neighborhood were digging bomb shelters and stocking them with nonperishable food. In contrast, today’s students are being told what clothes to pack when they travel to Moscow and Beijing on school trips. Basements, these days, are for game rooms stocked with flat-screen TVs, XBox consoles and snacks. It seems the negotiated de-escalation of the nuclear arms race has been successful. I hope that in medicine, we can follow this example. Maybe if we learn to negotiate, we won’t be so mad.

—Dr. White is Chief of Surgical Services, VAMC, and Professor of Surgery, George Washington University, Washington, DC.

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Money for Drugs

Part 2 of a 3-Part series

Should Physicians Be Paid for Pharmaceutical Development and Clinical Investigations?

[Editor’s Note: The following article was originally published in Missouri Medicine, September/October 2011;108:321. It has been edited slightly for in-house style.]

medicine lost its moral no Has Compass? by art gale, mD Two former editors of The New England Journal of Medicine (NEJM), Marcia Angell, MD, and Jerome Kassirer, MD, wrote separate books, both published in 2005, on how financial conflicts of interest involving physicians and the pharmaceutical industry have undermined the validity of clinical research and compromised the integrity of the medical profession.

Dr. Angell’s book is titled “The Truth about Drug Companies” (Random House Trade Paperbacks; 2005) and Dr. Kassirer’s book is “On the Take” (Oxford University Press, USA; 2005).

Each work takes a slightly different approach. Dr. Angell focuses mainly on drug companies, whereas Dr. Kassirer’s book focuses mainly on physicians.

Both authors document the wellknown practices drug companies use to entice physicians to prescribe their products. These include gifts, dinners at expensive restaurants and payments to be a “consultant” in name only.

Dr. Angell also discusses at length the role of contract research organizations that establish networks of practicing physicians who perform clinical studies. There are approximately 1,000 such organizations. They receive revenues of about $7 billion annually from their drug company clients. In 2001, these organizations offered bounties to physicians that averaged about $7,000 per patient enrolled. In one trial, physicians were offered $12,000 per patient and another $30,000 on enrollment of a sixth patient. Many of the drugs tested are already approved, so-called postmarketing or Phase IV studies.

With decreasing reimbursement from managed care and increasing professional liability premiums, one can understand why so many doctors enroll their patients in these trials. A physician can make much more money from clinical trials than from seeing patients. And the work is a lot easier.

is Crucial for yes Cooperation lifesaving medications

Many critics view these studies as just excuses to pay doctors to put patients on a company’s already approved drug.

The authors reserve their harshest criticism for their colleagues in academia.

As former editors of one of the world’s premier medical journals, Drs. Angell and Kassirer have reviewed hundreds of articles submitted for publication and are eminently qualified to analyze clinical investigators and the conflicts of interest that affect their research.

Dr. Angell writes, “Until the 1980s, researchers were largely independent of the companies that sponsored their work. Now, however, companies are involved in every detail of the research ... even whether to publish the results.”

She thoroughly documents the financial relationship between academic medical centers, especially her own (Harvard) and the drug companies.

Harvard is hardly unique. Two-thirds of academic medical centers hold equity in companies that sponsor some of their research. The academic medical centers reap huge profits from these arrangements. They also receive major gifts and endowments from the drug companies. But there is a price to pay. In Dr. Angell’s view, researchers become little more than “hired hands” of the pharmaceutical industry. She concludes “all of this makes a mockery of the traditional role of researchers as independent impartial scientists.”

Both authors cite a particularly egregious example of authors’ financial ties to drug companies. These ties were so extensive that there was insufficient see ”no” page 42

b y m arJorie P oWell , JD Physicians play a vitally important role in conducting clinical trials of potential new medicines and helping to explain new treatments and how they work to other health care providers.

Collaborations between biopharmaceutical research companies and physicians at respected research institutions have been critical to the development of clinical trials of new medicines for years.

The United States leads the world in the development of new medicines and most of the drugs that U.S. companies have created are still on the market today saving and enhancing the lives of millions of patients and helping to control the costs of surgery and hospitalization.

Clinical trials are crucial to determining the safety and effectiveness of new medicines, and are an essential part of the increasingly expensive 10- to 15-year drug development and approval process. Biopharmaceutical companies often turn to physicians at respected academic medical centers, including the University of Missouri School of Medicine, the University of Kansas Medical Center and the Washington University School of Medicine in St. Louis, to conduct their clinical research.

The clinical testing database of the NIH shows that in the arena of new cancer medicine development alone, these three respected institutions are conducting nearly 70 trials of potential new

anticancer drugs in collaboration with biopharmaceutical companies.

University medical centers attract some of the nation’s best physician clinicians and researchers. This finite pool of talented physicians is precisely the dynamic, experienced expertise companies want, and need, to conduct their clinical trials. Importantly, extensive safeguards exist to protect the interests of patients, help avoid biased clinical trial results and maintain the highest standards of medical research ethics.

FDA regulations are in place and detailed guidelines have been provided by the NIH and the medical schools themselves to help assure that clinical research is conducted in a way that protects all participating patients. At the University of Missouri School of Medicine, for example, all clinical tests of new medicines are reviewed and approved by an institutional review board and all faculty members are required to submit conflict of interest reports that disclose all outside activities and relationships, including involvement in clinical trials of new medicines being developed by biopharmaceutical companies.

The Pharmaceutical Research and Manufacturers of America (PhRMA), meanwhile, provides its “Principles on Conduct of Clinical Trials and Communication of Clinical Trial Results” to help ensure that clinical research sponsored by biopharmaceutical companies is carefully conducted and meaningful research results are published for health care professionals and patients.

Revisions to the Principles, put in place nearly two years ago, call for increased transparency about clinical tests for physicians and their patients and improved disclosure to better manage potential conflicts of interest in medical research.

Some critics, who ignore the many effective efforts to protect the integrity of clinical trial data, insist that only tests conducted by the NIH are truly unbiased. They overlook a key fact: NIH officials have repeatedly acknowledged that their institutes are not equipped to conduct the thousands of clinical tests needed for the development of new medicines every year. see ”yes” page 42

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42

opinion

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

continued FroM pAGe 41

to publish them in print. no room Instead, they had to be published on NEJM’s Web site, where they consumed three single-spaced typewritten pages!

Conflicts of interest extend even to the venerable National Institutes of Health (NIH). In 1995, the director of the NIH, Harold Varmus, MD, “quietly rescinded the policy that barred NIH directors from accepting consulting fees and stock options from companies.” As a result, directors of various institutes have earned hundreds of thousands of dollars in “consulting” fees. For example, the deputy director of the NIH Laboratory of Immunology, whose salary was $179,000 in 2003, earned $1.4 million in consulting fees over 11 years and received stock options valued at $865,000. Other senior scientists with ties to industry included the director of the National Institute of Arthritis, a director of the National Institute of Diabetes and Digestive and Kidney Disease and the former director of the National Human Genome Research Institute.

How can physicians believe anything that they are told by so-called experts when they learn that clinical guidelines are based on flawed research that may not be independent and objective?

When these revelations were published, a former acting director of the NIH opined that none of these revelations compromised the public interest because NIH scientists are “highly ethical people with enormous integrity.”

Dr. Kassirer quotes the current director of NIH, Elias Zerhouni, MD, who found no evidence that “medical decisions had been influenced by company payments to agency officials.” After Congress promised a full investigation, Dr. Zerhouni changed his mind and said that NIH top scientists were no longer accepting consulting fees or stock options.

The conflict of interest in clinical research is so pervasive that, as editor of the NEJM, Dr. Kassirer had difficulty finding independent authors to write review articles. In the late 1990s, he stated, “We occasionally had to reject five or six prominent authors before we found one who had no conflicts.” His successor at NEJM solved this problem by changing the policy because he found it too difficult to find authors who were free of such conflicts.

What do all the conflicts of interest

have to do with the practice of medicine?

The answer is: a lot. Probably their most important effect is through the development of clinical guidelines—guidelines that practicing physicians are supposed to follow in treating patients.

The government and industry now are promoting “evidence-based medicine.” But has anyone asked where the “evidence” comes from? It often comes from the same conflicted studies by the same conflicted clinical investigators just described. How can physicians believe anything that they are told by so-called experts when they learn that clinical guidelines are based on flawed research that may not be independent and objective?

Dr. Kassirer cites two physicians, one the dean of Cornell Medical School in New York City and the other chief of cardiovascular medicine at Brigham and Women’s Hospital in Boston, as examples of experts who are promoting stricter guidelines for blood lipid levels. Both have financial ties to Pfizer. Dr. Kassirer asked one of the physicians, Peter Libby, MD, of Brigham Hospital, why he lent his distinguished name to brochures and Web sites that promote lipid-lowering drugs. Dr. Libby replied that it is a way to spread an educational message that he believes in. He believes that by disclosing all of his financial conflicts of interests he can maintain his “independence, objectivity, and reputation.” According to Dr. Kassirer, Dr. Libby “asserts that he exploits a corrupt system in a way that benefits patients.” Apparently, Dr. Libby and other “distinguished” researchers hold to the discredited tenet that the end justifies the means.

On a more personal level, when drug reps come into our offices, they present studies that show why their drug is the best. Most of these studies are sponsored by drug companies and are conducted by, to quote Dr. Angell again, “hired hands,” and therefore are suspect. When I asked a drug rep recently whether his company sponsored a study he was citing, he replied, “Of course, what did you expect?”

Most practicing physicians are well aware that they cannot always take the word of the drug reps at face value. So why make a big fuss about it? The facts are that the pharmaceutical industry spends far more on marketing than on research. Their marketing is effective or they wouldn’t spend so much money on trying to influence physicians. The ultimate cost of all these suspect drug studies is borne by our patients—often our Medicare patients, who can least afford the drugs that are being promoted.

Drs. Angell and Kassirer do not deny that many products of the pharmaceutical industry have improved the lives of see ”no” page 43

The NIH and its grantees yes conduct vitally important basic

presented and that materials contain legitimate information. Strict federal research that can be used by biopharma- regulations and self-imposed stringent ceutical companies to help develop new industry standards are already in place medicines. But actual drug development, to ensure the accuracy of discussions including preclinical and clinical testing, and documents offered during indusis the expensive and time-consuming try–physician interactions. The FDA responsibility of our nation’s innovative requires that materials be “truthful, accudrug companies, which must spend tens rate and consistent with product labelof billions of dollars annually to get the ing” approved by the agency. Companies job done. are held accountable for the presentaIn 2010, America’s biopharmaceutical tions of their speakers. Biopharmaceuresearch companies spent a record $67.4 tical research companies and PhRMA billion on research and development. have launched a number of wide-rangAnd various estimates show that clini- ing efforts to help guarantee compliance cal trials account for 45% to 75% of total with federal rules and industry standards. pharmaceutical development costs. Our For example, the PhRMA Code on drug development and approval process Interactions with Healthcare Professiontoday, one that is carefully monitored by als says company decisions to hire phythe FDA, is working well. And perhaps sicians as speakers should be based on the best evidence of the system’s success the doctors’ medical knowledge, experis the progress that has been made in the tise in a particular therapeutic area, comfight against disease that can be, in large munication skills, faculty and medical part, attributed to new society affiliations, parin the end, the medicines. For examticipation in clinical trials ple, the development and reputation. contentions of of new heart disease For their part, the our critics distort many biopharmaceutical and stroke medicines has helped to reduce companies adhering to the value of deaths from these two the PhRMA Code conmajor killers by near- company–physician duct periodic reviews of ly 30%. New anticanspeakers to determine if interactions and cer drugs, meanwhile, they are complying with worse, threaten to FDA regulations and have contributed to an increase in cancer surjeopardize patient their own ethical complivivors from 3 million ance policies. The speakcare. in 1971 to 11.7 million ers may be fired if they in 2007. violate federal rules or Physicians learn about new medicines company policies. Biopharmaceutical from a range of sources, including first- research companies are also commithand experience, medical journals, con- ted to transparency in their relationships tinuing medical education programs with health care professionals. PhRMA and discussions with biopharmaceuti- and its members supported recent Concal company representatives and fellow gressional transparency efforts, includphysicians at company-sponsored meet- ing enactment of the Physician Payment ings. PhRMA agrees with the American Sunshine Act. Several companies have Medical Association, which in Congres- voluntarily released information about sional testimony said, “There is a clear payments to doctors before implementaneed for interactions between physi- tion of the Sunshine Act. cians and the pharmaceutical industry When the law is fully implemented in to ensure the free flow of valid scientif- 2014, drug companies will be required ic information. When the information is to provide a thorough listing of payaccurate and complete, physicians have ments or other transfers of value to phythe necessary tools to make the right sicians and teaching hospitals to the U.S. prescribing decisions.”

Department of Health and Human SerWhen physicians meet with biophar- vices, which will post the information maceutical company representatives or on a federal Web site. Additionally, the attend events at which fellow physicians PhRMA Code, which was strengthened explain medicines and how they work, in July 2008, requires that health care they are given the latest FDA-regulated providers serving on committees that information about the benefits, risks and establish clinical guidelines or formularappropriate uses of drugs. At physician ies must disclose to the committees their speaker forums, health care providers can speaking and consulting arrangements discuss this important information with with biopharmaceutical companies. a peer who has firsthand knowledge and In the end, the contentions of our critexpertise in the therapeutic area being ics distort the value of company–physician discussed. That interaction helps to interactions and worse, threaten to jeopimprove knowledge and patient care. ardize patient care. Allegations that the It is, of course, vitally important to promotional efforts of biopharmaceutical see ”yes” page 43 guarantee that sound scientific data are

opinion 43

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

money For DrugS Continued from page 43

Nor do they deny the imporno patients. tance of the researchers, often physi-

cians, in developing these products. But Dr. Kassirer believes that pharmaceutical companies, in their lust for profits, have crossed the line between “advancing the cause of science and the betterment of patient care on the one hand and the pecuniary interests of physicians on the other. Too many physicians have become mere tools of industry’s promotional and marketing efforts. Others have engaged in pseudoscientific studies and published biased articles that foster industry’s goals over patient goals.”

The final sentence in Dr. Angell’s book sums it up: “Nowadays, even the most distinguished and apparently unbiased academics may be on the pharmaceutical industry’s payroll. If they are, you need to be especially skeptical about their pronouncements.”

As we enter the third millennium, is this the kind of reputation we want our profession to have? Do we want future generations to look back and say we were, in Dr. Kassirer’s words, “on the take”? If we have lost our moral compass, we need to regain it.

In their concluding chapters, Drs. Angell and Kassirer make specific recommendations on ways that the pharmaceutical industry and the medical profession can reclaim the high ground. But they have a healthy skepticism that this can be accomplished. Their books are more directed to the public than to doctors or drug companies. They believe that the public needs to learn the facts. The message is clear: If we as profession do not police ourselves, the pubic eventually will.

Disclosures: None reported.

—Dr. Gale practices internal medicine in St. Louis. unduly influence physiyes companies cian prescribing and help to drive

up health care costs are contradicted by a simple fact: 78% of the prescriptions written today are for generic drugs, not brandname medicines.

The educational programs of biopharmaceutical firms help to make physicians aware of appropriate, often newly FDA approved, medicines and their proper uses. Their arsenal of weapons to treat and prevent disease is growing, and that means better patient care.

Disclosures: None reported.

—Marjorie Powell, JD, is senior assistant general counsel at Pharmaceutical Research and Manufacturers of America.

yes soros’ money in Campaign against Physicians receiving research Funds should Be Disclosed

b y J ohN c. h agaN iii, mD Much of the agitprop generated in the media and fourth estate originates from the Center on Medicine as a Profession (CMAP). “CMAP was established in October 2003 at the Columbia College of Physicians & Surgeons through a joint agreement by

Figure Comparing r&D spending with FDa approvals, page 50 the Institute on Medicine as a Profession (IMAP) and Columbia University. In February 2003, George Soros, Chairman of the Open Society Institute, generously funded the establishment of IMAP with a gift of $7.5 million. CMAP carries out IMAP’s programmatic agenda.”1 This connection with Soros, a financier who is spending many billions of dollars attempting to reshape the world into his view of a leftist utopia, is rarely

to never disclosed by Soros-compensated physicians doing his bidding, nor the journalists that use CMAP for source material and physician quotes. This is disingenuous, hypocritical and completely undermines CMAP credibility. reference 1.

http://www.cmap.columbia.edu/index.shtml

—Dr. Hagan is the editor of Missouri Medicine and an ophthalmologist in Kansas City, Missouri.

44

letters to the editor

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

money for Drugs

our efforts. Rather than address the bias that may exist in the physician–pharma relationship, why not focus our energies To the Editor: I read with some dismay the “Money on a much larger, much more pervasive for Drugs” discussion in the December and destructive biased relationship?

2011, issue of General Surgery News (page I am speaking of course about the 26). I am a private practice diagnostic specter of Big Government, not only and interventional radiologist, and the over the doctor–patient relationship, son of a retired general surgeon. I am a but the entire practice of medicine and simple man, and when confronted with structure of health care as it exists today. complex situations, I try to break them The deleterious effects of corporate and down into their most commercial influence on fundamental, simple the deleterious effects of medicine are dwarfed by elements in an effort corporate and commercial the blanket of oppressive government intervention to gain clarity. influence on medicine are that has fueled the decline In the pro/con dwarfed by the blanket of of our profession in the discussion by Drs. Van oppressive government name of the public good.

Way and Bohigian, I While the motivating am encouraged to see intervention that has that both authors are fueled the decline of our bias of politicians and policymakers can often set on establishing profession. be labyrinthine and and preserving the cryptic, it can also be virtue of service to the patient as top priority. On that, I readily apparent to those who simply think we all agree. But, on the matter of open their eyes and look. For example, so-called Big Pharma and the potential the most glaring conflict of interest for harmful bias, I am compelled to point in politics is that most law makers are out the obvious: Efforts to completely lawyers. Tort reform anyone? Ponder extinguish bias are futile, as it is part of that one, and then explain to me why we human nature and cannot be eliminated. should engage in any handwringing over I am not saying we should not try. a $1,000 honorarium.

The discussion in your Money for Instead, I am suggesting that we redirect

Drugs series is important and timely. I simply wish to step back and add some perspective. The thrust of my argument is simple: If we are going to address the evils of bias, let us first take aim at the biggest of those threats to ourselves and to our patients. Let us address these smaller threats but not be distracted by them. Let us demand effective selfregulation and self-discipline not only on the part of physicians but also corporate shareholders and corporate governance.

And finally, let us not just chip away at the toxins that decay our profession, but instead confront head on the undeniable bias of government and the cancer of imposed government regulation while it is offered as a cure.

Ronald B. Workman Jr., MD Huntsville, AL

Posted @ generalsurgerynews.com

spam in a Can [Re: Spam in a Can, January 2012, page 1] As usual, Dr. [David] Cossman’s writing is insightful, literate, witty and thought-provoking. But I wonder if the current trends in surgical practice are

due more to generational differences in attitude rather than organizational and political mandates. Young surgeons today simply do not have the same goals and aspirations as those of us who trained 30 or 40 years ago. They don’t seem to care about swagger, or about being “heroes.” Is this good or bad for the profession? I’m not sure. The more important question is: Is it good or bad for patients? I think the jury’s still out on that one.

As far as the comments of “patri...” are concerned, the government is only a small part of the problem. I agree with Dr. Cossman that accountable care organizations are doomed to failure, but part of “Obamacare” addresses a very real problem in this country by providing access to care for millions of people who did not have it before. We will never see a return to the old, unbridled, fee-forservice system, and for good reason. As medicine has become more and more technology driven, it has simply become too expensive for people to pay for on their own. Actually, it’s partly the result of capitalism that we are in so much trouble—the insurance companies have cleverly used managed care to line their own pockets at our expense.

Posted Jan. 19, 2012

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opinion 45

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

50 Tips for Coping With Burnout, Aging in Surgical Practice 2.

4.

M b y m oShe S cheiN , mD, FacS

uch has been written recently about burnout among surgeons and how they can cope with it (Ann Surg 2009;3:463-471; Adv Surg 2010;44:2947). Although some studies point to a higher rate of burnout among younger surgeons, common sense suggests that the more we engage in a demanding activity, the more likely we are to become fed up with it. The same can and does happen in any arduous and stressful profession. An infantryman rotting in the trenches—without significant periods of rest and relaxation—will develop physical and emotional fatigue.

He will burn out.

When general surgeons finally become well trained and self-sufficient after medical school, residency, fellowships and early years in practice, they are not so young anymore. Just take a back seat in the auditorium at an American College of Surgeons meeting or in your own departmental Morbidity and Mortality conference, and calculate the small percentage of attendees who do not sport a bald spot or gray hair—yes, dyed hair is easy to spot. This sight may make many of you ponder your imminent senescence, if it’s not already at the gate.

This article presents a few points, not in order of importance, to help you combat burnout and to achieve graceful aging in surgery. The list is based on my own experience of 32 years in this profession. Having survived the chaos of moving across continents, counties, various practices, and political upheavals, I have found peace of mind and some degree of stability while in the pre-winter of my surgical career.

This list of recommendations may sound tacky or cheesy, pretentious, repetitive and cliché-laden to the highbrows among you. Without doubt, only saints could comply with all the stipulations.

Surgeons, including myself, are rarely saints; nevertheless, I hope these observations and recommendations might be beneficial to some of you. I’ll bet that many of you could add more items to the list.

(Note: All quotations and aphorisms by surgeons in this article are from my books: Aphorisms and Quotations for the Surgeon [2004] and A Companion to Aphorisms and Quotations for the Surgeon [2008].

“For surgeons, an old man is somebody 10 years older than you.”

—Avi Shapira, MD Recognize, be aware, and admit that yes, you are aging.

1.

“Don’t constantly chase money. Don’t get greedy. Cure yourself of the obsession to produce more relative value units.

You did not become a general surgeon to be a millionaire. Be satisfied with what you have. A young doctor’s chief practice is the practice of economy”—J. Chalmers Da Costa, MD; but at your age it should not be like this anymore.

Save and invest carefully. Solid retirement plans will provide security and relieve stress.

“A surgeon can continue to operate as long as his hand is steady and his eye keen. Hand and eye are apt to fail in the 60s.”—Dr. Da Costa.

Recognize and acknowledge your aging physiology. Don’t do more than you can cope with and don’t over-commit yourself.

“And middle-of-night aneurysms never failed to leave his nerves jangling like a steel on speed. As a young man he could catnap on a washing line,

5.

3.

yet be instantly awake when necessary; but now at 58, his old bones took longer to settle and even longer to spring into action.”—Mike Albany, MD Plan your schedule carefully. Acknowledge that you are no longer the tireless-around-the-clock-I-can-do-itall-surgeon. Your strained body, particularly your central nervous system, needs longer periods of rest and sleep to recover properly. see AGinG surGeon page 46

Scan the QR code with your smart phone to catch up on the latest news anywhere!

Next stop: GeneralSurgeryNews.com ®

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46

opinion

GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

aging Surgeon continued from page 45

6.

Avoid decision fatigue. Decisions made early during the day tend to be wiser. Start with the most difficult case, and do the other major case another day.

And instead of doing five cases per day, satisfy yourself with two.

“Surgeons who take unnecessary risks and operate by the clock are exciting from the onlooker’s standpoint, but they are not necessarily those in whose hands you would by preference choose to place yourself.”—Theodor Kocher, MD Don’t rush, and do not allow yourself to be rushed by others. Ignore the watch.

Who cares if the nurses whisper “uf, look how slow he is. … Dr. Kumar would have finished that lap chole already an hour ago.” Operate at leisure and enjoy yourself.

Be aware that advanced age tends to be linked with growing impatience and diminishing attention span. Hence, be extra cautious with each operative step. Banal, preventable complications are inherent in the younger surgeon’s practice but it should not happen to someone with your experience.

Adapt to the physiologic limitations of your advancing age. There is nothing like a power nap to bring vigor back to your brain. Try dozing 10 to 20 minutes in your office between long cases, or after lunch. If you don’t have a bed, use a recliner, or get a pillow and lie on the carpet. Don’t be embarrassed about the need to snooze. Instead, let your staff know that “the old guy is taking a nap.” It is better than being a “tired old surgeon.”

Avoid operating through others.

You may be blessed with a team of dedicated disciples, younger partners or superb chief residents. But do not embark on lengthy and complex procedures because they can assist you. Let them do whatever they are trained and able to do, but take responsibility only for operations you could start and complete by yourself if you were alone. Do not let them murmur behind your back, “the old man took the credit while I had to do the operation for him.”

“The young physician starts life with 20 drugs for each disease, and the old physician ends life with one drug for 20 diseases.”

—William Osler, MD Similarly, the greenhorn surgeon knows about numerous surgical options for each condition, but when aging, he adheres to the one option that he can do best. This is the way to go: Stick to procedures you are comfortable with.

Just because your younger partner can remove the pancreas through a singleincision laparoscopy does not mean that

23. adapt to the physiologic limitations of your advancing age.

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it at least 30 minutes a day. Being physically fit will improve and preserve your performance in and out of the operating room.

Nourish yourself properly. Plan your meals. Bring your lunch from home: a nutritious sandwich or a box of salad rather than helping yourself from the tray of sugary cookies at the nursing station. Enjoy what you eat: Everything in moderation is OK, as long as it makes you happy. Avoid overeating or else you will be huffing and puffing when operating on obese patients. And what example will you serve to your patients? However, do not forget that a small amount of pure sugar at the end of the working day may help combat decision fatigue.

Do not deprive yourself of small doses of “poisonous” treats. Despite the current politically correct guidelines, a glass of wine at dinner is OK even when you are on call. And the occasional cigar won’t kill you. Aging surgeons are not fakirs [ascetics].

Get yourself a good physician, preferably the best internist or family doctor in your environment. See him or her formally, avoiding curbside consults. And don’t forget your daily dose of aspirin.

“Young surgeons err in believing that knowledge can compensate for lack of experience; old surgeons err in believing that experience can compensate for lack of knowledge.”—Unknown Preserve your mind. This does not mean watching television and movies.

Engage in intellectual pursuits, and continue to be inquisitive and critical. Read, read, read.

“In the lecture hall he preaches what he heard at the last association meeting, but in practice he continues to do what he did since his residency.”—Unknown Practice what you preach. Do not succumb to the “old chairman syndrome.”

“The keen clinician, as he grows in experience, becomes more and more valuable as age advances.”—William J. Mayo, MD Cherish your well-deserved role as the elder statesman. Be proud of your new role as one of the local old wise men.

Stand and speak up, if necessary, in support of your colleagues and staff. At your age, you mustn’t be hesitant combating injustice.

“When a man falls into his anecdotage, it is a sign for him to retire.”—Benjamin Disraeli, MD Know when to offer your opinion and when to shut up.

“Hardening of the attitude occurs before hardening of the arteries.”—Unknown Try not to be dogmatic.

now you have to try and do the same.

Leave surgical acrobatics (e.g., natural orifice transluminal endoscopic surgery) to the younger and less wise.

“Young surgeons, busy mastering the technicalities of the art, are particularly alert to seize every legitimate opportunity to practice technical maneuvers, the more complicated the better.”

—Stanley O. Hoerr, MD But by now you must know better.

Avoid gimmicks—leave the doubtful glory of robotic ventral hernia repair to others. Do it the best way—your way!

“The old surgeon … knows that the mortality published as 2%, at best, is such only in the hands of the most experienced operators, and finally most likely the statistics are wrong.”

—Arthur E. Hertzler, MD Avoid the stress of learning and doing a “new operation” only because somebody has described it.

“Once you start studying medicine, you never get through with it.”—Charles H. Mayo, MD Do not become obsolete. Keep updating yourself about the modern practice of surgery until you retire or drop dead.

Know more about the procedures you choose not to do than those you prefer to do.

We know that you can do it all.

But now learn to refer to people who can do it even better. Accept that you are not an almighty God, but just a humble human being who cares for the safety of your patients and your own health.

The older you become, the more cases you should refer out, not only for the sake of the patient but for your own sake.

“Everything in surgery is patient selection—the chief determinant of mortality and morbidity.”—Unknown It does not matter that 10 years ago, you could do a Whipple in two hours.

Now that you are 67 years old, you have the option to select out of major cases like this one. You do not need people saying, “What is that old fart doing? Can he still

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do it?”

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“Many people like their doctors moldy like their cheese.”—Oliver Wendell Holmes, MD Not all is lost! Many patients will appreciate your seniority and seek your counsel. Cherish their trust and treat them with compassion. By now you probably agree that basic surgery, like relieving the pain of an anal fissure or removing a perforated appendix, is no less beneficial to the patient than a laparoscopic sleeve gastrectomy. Be happy with your new role as a bread-and-butter surgeon.

Do not try to look much younger than you are. A new set of perfect, white, glossy teeth when combined with a wig and a facelift will make you look pathetic—a laughingstock of your department.

Relish your white hair because it reflects experience. Let your younger colleagues enjoy their glory (of doing 101 bariatric procedures per month, while presenting three abstracts in Melbourne, Acapulco and Rome). You do not need such distractions anymore. You are now wise enough to realize that doing three appendectomies, a pilonidal or two and reading a nice fat novel are more satisfying and soothing.

Take care of yourself. A neglected old man appears older than he actually is. Although a two-day beard looks cool on a movie star, it makes you look like a hobo. Long and wavy white hair may be fashionable among Continental intellectuals, but you will look more youthful and vigorous with welltrimmed hair.

Dress appropriately to your specific type and location of practice.

Try to look respectable but do not overdo it: A rural surgeon wearing a three-piece Pierre Cardin suit looks ridiculous.

Take care of your body. Exercise every day. Do it sensibly so as not to overburden your aging joints. Walk, bike, swim, golf, kayak, cross-country ski and avoid the elevator—whatever, but do

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see AGinG surGeon page 50

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GENERALSuRGERYNEWS.COM / GENERAL SuRGERY NEWS / FEBRuARY 2012

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opinion aging Surgeon continued from page 46

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“Every Chief of Service should have a pet dog.

When he retires from the hospital, he should leave his dog on the floor of the department he served, because when he returns the only one who will recognize him will be his dog.”—Béla Schick, MD Get yourself a dog long before you retire to help fill the void after your kids have left your nest empty.

By now, you have earned the right to be a grumpy old man. But these days you are not allowed to be grumpy. Grumpiness combined with arrogance is particularly bad.

Smile as much as possible and be kind—to everybody! That includes nurses, scrub technicians, janitors and secretaries. As your light dims, the supporting staff could be your best advocates. As you age, it’s better to stop playing the surgical cockerel; instead, assume the role of the benign and charming surgical grandfather.

“Be kind to people on the way up—you’ll meet them again on your way down.”—Jimmy Durante Be extra gentle to younger colleagues, whether they are surgeons or not. Teach them by example and do not expect anything in return. Don’t be upset if they don’t recognize “who you really are” or “who you were.”

Do not cite repeatedly from your own studies and publications. Do not force copies of your manuscripts or books on your younger colleagues, residents, or students. For most of them, your past academic achievements belong to history as you will soon.

Don’t criticize younger doctors for their clinical errors. You can suggest politely that “things could have been done differently,” but do not disparage them.

By now, you must know that errors and delays in diagnosis and treatment are part of the game. Yes, they could have called you about the perforated appendix before you have left for the day; sure, they could have diagnosed the colonic obstruction already three days ago and not on Friday afternoon. But this is life and you cannot change things. There always will be good doctors and bad doctors. Be happy that you are doing things right!

“What to do with the competent but physically limited old surgeons? Make them administrators—they’ll still make mistakes, but won’t cause any bleeding.”—Andy Gage, MD Avoid conflicts. Shun nonsurgical stressful situations.

In fact, surgical emergencies have a calming effect on most of us. For example, if your nature is argumentative, avoid talking at Morbidity and Mortality meetings. But if sitting at brainstorming meetings calms you down, gradually quit surgery and become a full-time administrator.

Change your roles as necessary. In our profession, we can and should move around and move on. Why suffer in Cleveland, where everybody wants to screw you. Move on to Florida! Working in a hateful environment reduces your longevity.

Relocate to the countryside. There is a growing shortage of rural surgeons in the United States.

Why do you need to compete with the nearby hernia or breast centers of (so-called) “excellence” for every hernia or lumpectomy? When you become the lone surgeon in the county, all hernias and breasts will be yours.

Rural surgery can provide the optimal environment for the aging but still vigorous and competent surgeon who wishes to unwind in a kinder environment.

Cherish your family life. The extreme importance of a stable family life to the surgeon’s wellbeing does not need further emphasis.

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There are studies suggesting that having a spouse who works as a health care provider contributes to surgeon burnout. Obviously, it is more relaxing to talk at home about literature or music rather than about the last case or hospital politics. Well, at this stage it is too late to choose another spouse—or is it?

“When I was younger, I always told the residents that the first sign of senility in a surgeon is when he demonstrates an interest in surgical history.”—Leo Gordon, MD This is of course nonsense: The more our younger colleagues know about the surgical past, the less they would be inclined to reinvent the wheel.

Learn to turn off your Smartphone or laptop intermittently. While spending a week with your wife in Tuscany, there is no need to check your hospital email. Addiction to electronic devices is exhausting.

“Although a doctor may be in the winter of his years, the icicles should never gather in his heart and the lamp of pity should never be extinguished in his soul.”—J. Chalmers Da Costa, MD Be optimistic and proud of what you are doing. Yes, it is often frustrating for us old surgeons to adjust to the brave new world of surgical practice: the younger generation’s decreased sense of commitment to the profession, the rampant political correctness, the new leadership boasting administrative skills rather than surgical greatness. But let us continue enjoying what we are doing best—saving lives and relieving suffering—as long as we can.

Don’t dwell nostalgically on the good old days when giants (you among them) walked the earth.

Accept that times are changing and you are as well.

“Shakiness of the hand may be some bar to the successful performance of an operation, but he of a shaky mind is hopeless.”—William Macewen, MD But, “when a surgeon is old enough to have experience, that’s all he’s got going for himself.”—Unknown How true! But both deteriorating mental and physical capacities should make you think about retiring.

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“Incompetence does not necessarily come with age. Generally, the incompetent physician was that way from the start of his career. What comes with age are stiff fingers, perhaps a tremor, less visual acuity, diminished endurance, losing technical skills as a result.”—Dr. Gage Don’t wait until the operating room nurses whisper behind your back. Don’t wait until your colleagues, like Cromwell in Parliament (1653), said: “You have sat here too long for any good you have been doing lately. …

Depart, I say; and let us be done with you. In the name of God, go!”

“Surgeons of old experience … consciously or subconsciously long for the day when they shall do their last operation.”—Dr. Hertzler Plan your retirement in advance and carefully. We all know it is coming; rather than being forced out, let us hang up the gloves voluntarily and gracefully, when the time comes.

“The young man knows the rules, but the old man knows the exceptions. … The young man feels uneasy if he is not continually doing something to stir up his patient’s internal arrangements. The old man takes things more quietly, and is much more willing to let well enough alone.”—Dr. Holmes But please do not retire too early. You can still do much good! Rather than retire, consider gradually decreasing your workload: A day off in the middle of the week could rejuvenate your systems. Do not keep postponing gratification: Start taking pleasure in life earlier and this will prolong your satisfactory career as a surgeon.

Generally, calm down and try to enjoy each day as it comes. Have fun until your last surgical day.

What to do after that is another story.

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I wish to thank David Dent, MD, of Cape Town, South Africa, Paul Rogers of Glasgow, United Kingdom and members of SURGINET for their invaluable input.

—Dr. Schein is a general surgeon in Ladysmith, Wisc.

money for Drugs

As Resarch and Development has increased the number of drugs approved by the FDA has decreased, 1996-2006.

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