Romjoh 7 (2) 2015 by Innovation in Health Center

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T H I S J O U R N A L I S I N T E R D I S C I P L I N A R Y A N D I S D E D I C A T E D T O A L L S P E C I A L I S T S I N T H E M E D I C A L F I E L D R E L A T E D T O O N C O LO GY A N D H E M A T O LO GY

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Volume III I Issue 2 I 2015

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IBI Factor: 2,66

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BDI INDEXED: IBI Factor: 2,66

GIF Factor 2013 - 0,452 GIF Factor 2014 - 0,595

Editor-in-Chief & Managing Editor

Şef Lucrări Dr. Lucia Stănculeanu (Universitatea de Medicină şi Farmacie “Carol Davila”, Bucureşti, România)

Editor-in-Chief Assistants

Dr. Raluca Bunghez, Institutul Oncologic “Prof. Dr. Al. Trestioreanu”, Bucureşti Dr. Bogdan Georgescu, Institutul Oncologic “Prof. Dr. Al. Trestioreanu”, Bucureşti

Senior Editors Medical Oncology Prof. Dr. Rodica Anghel (Universitatea de Medicină şi Farmacie “Carol Davila”, Bucureşti, România) Prof. Dr. Florin Bădulescu (Universitatea de Medicină şi Farmacie Craiova, Craiova, România) Şef Lucrări Dr. Simona Mihuţiu (Universitatea de Medicină şi Farmacie Oradea, Oradea, România) Oncological Surgery Prof. Dr. Eugen Brătucu (Universitatea de Medicină şi Farmacie “Carol Davila”, Bucureşti, România) Conf. Dr. Nicolae Dan Straja (Universitatea de Medicină şi Farmacie “Carol Davila”, Bucureşti, România) Hematology Prof. Dr. Anca Roxana Lupu (Universitatea de Medicină şi Farmacie “Carol Davila”, Bucureşti, România) Paediatric & Oncology Conf. Dr. Monica Dragomir (Universitatea of Medicină şi Farmacie “Carol Davila”, Bucureşti, România) Radiology & Oncology Prof. Dr. Rodica Anghel (Universitatea de Medicină şi Farmacie “Carol Davila”, Bucureşti, România) Şef Lucr. Dr. Xenia Bacinschi (Universitatea de Medicină şi Farmacie “Carol Davila”, Bucureşti, România) Dr. Ciprian Enachescu (Centre Hospitalier Lyon Sud, Lyon, France) Gynecology & Oncology Prof. Dr. Alexandru Blidaru (Universitatea of Medicină şi Farmacie “Carol Davila”, Bucureşti, România) Conf. Dr. Alexandru Filipescu (Universitatea of Medicină şi Farmacie “Carol Davila”, Bucureşti, România) Asist. Univ . Dr. Mihai MITRAN (Universitatea of Medicină şi Farmacie “Carol Davila”, Bucureşti, România) Dermatology & Oncology Asist. Univ. Dr. Victor Gabriel Clătici (Universitatea of Medicină şi Farmacie “Carol Davila”, Bucureşti, România) ENT & Oncology Prof. Dr. Romeo Călăraşu (Institutul de Fonoaudiologie şi Chirurgie Funcţională ORL “Prof. Dr. D. Hociotă”, Bucureşti, România) Șef Lucr. Dr. Vlad Budu (Universitatea of Medicină şi Farmacie “Carol Davila”, Bucureşti, România) Stomatology & Oncology Prof. Dr. Marian Vladimir Constantinescu (Universitatea Titu Maiorescu, Bucureşti, România) Prevention & Screening Asist. Univ. Mircea O. D. Lupusoru (University of Medicine and Pharmacy “Carol Davila”; Director Medical - Spitalul de Psihiatrie Titan “Dr. C-tin Gorgos”)

Romanian Editorial Board

International Editorial Board

Prof. Dr. Oltean Galafteon (Universitatea of Medicină şi Farmacie Târgu Mureș, Târgu Mureș, România) Prof. Dr. Tudor-Eliade Ciuleanu (UMF “Iuliu Haţieganu” Cluj-Napoca) Prof. Dr. Lucian Miron (UMF „Gr. T. Popa” Iaşi) Prof. Dr. Ljubomir Petrov (Universitatea of Medicină şi Farmacie „Iuliu Haţieganu”, Cluj-Napoca, România) Prof. Dr. Ioniță Hortensia (Universitatea of Medicină şi Farmacie “Victor Babeș” , Timișoara, România) Prof. Dr. Cătălina Poiană (Universitatea of Medicină şi Farmacie “Carol Davila”, Bucureşti, România) Conf. Dr. Coriu Daniel (Universitatea of Medicină şi Farmacie “Carol Davila”, Bucureşti, România) Conf. Dr. Adriana Coliță (Universitatea of Medicină şi Farmacie “Carol Davila”, Bucureşti, România) Conf. Dr. Anca Coliţă (Universitatea of Medicină şi Farmacie “Carol Davila”, Bucureşti, România) Conf. Dr. Horia Bumbea (Universitatea of Medicină şi Farmacie “Carol Davila”, București, România) Conf. Dr. Elena Copaciu (Universitatea of Medicină şi Farmacie “Carol Davila”, București, România) Conf. Dr. Gabriel Kacso, (Universitatea of Medicină şi Farmacie „Iuliu Haţieganu”, Cluj-Napoca, România) Șef Lucrări Dr. Laura Mazilu (Facultatea de Medicină, Universitatea Ovidius, Constanţa, România) Șef Lucrări Dr. Andrei Coliță (Universitatea of Medicină şi Farmacie “Carol Davila”, Bucureşti, România) Şef Lucr. Dr. Laurenţia-Nicoleta Galeş (Universitatea of Medicină şi Farmacie “Carol Davila”, Bucureşti, România) Şef Lucrări Dr. Cristian Silviu Voinea (Universitatea of Medicină şi Farmacie “Carol Davila”, Bucureşti, România) Şef Lucrări Dr. Diana Paun (Universitatea of Medicină şi Farmacie “Carol Davila”, Bucureşti, România) Şef Lucrări Dr. Ioana Soare (Universitatea Titu Maiorescu, Facultatea de Medicină, București, România) Asist. Univ. Gabriela Elena Lupusoru (University of Medicine and Pharmacy “Carol Davila”) Asist. Univ. Dr. Nicolae Bacalbaşa (University of Medicine and Pharmacy “Carol Davila”) Asist. Univ. Dr. Carsote Mara (Universitatea of Medicină şi Farmacie “Carol Davila”, Bucureşti, România) Asist. univ. dr. Adina Alexandru (Universitatea de Medicina si Farmacie “Carol Davila”, Bucuresti, România) Asist. Univ. Dr. Trandafir Maria Silvia (Universitatea of Medicină şi Farmacie “Carol Davila”, Bucureşti, România) Dr. Adrian Udrea (Medisprof, Cluj-Napoca, România) Dr. Eugenia Carmen Lisencu – Institutul Oncologic “Prof.dr. Ion Chiricuţă”, Cluj-Napoca, România Dr. Radu Niculescu (Institutul Clinic Fundeni, Bucureşti, România) Dr. Ana Maria Boeru (Asociaţia Free of Pain, Bucureşti, România) Dr. Virgil Dincă (Asociația Română pentru Studiul Durerii, Bucureşti, România)

Prof. Dr. med. Anca-L. Grosu (Klinik für Strahlenheilkunde, Universität Freiburg, Freiburg, Germany) Prof. Dr. Shibo Li (University of Oklahoma Health Sciences Center, Oklahoma City, USA) Prof. Dr. Mariusz Z. Ratajczak (University of Louisville, Louisville, USA) Prof. Dr. Arnold Ganser (Hannover Medical School, Hanover, Germany) Prof. Dr. Saverio Bettuzzi (University of Parma Via Volturno, Parma, Italy) Prof. Dr. Lodovico Balducci (Moffitt Cancer Center, Tampa, USA) Prof. Dr. Leonard Wartofsky (Georgetown University School of Medicine, Washington, USA) Prof. Dr. Robert Amato (Memorial Hermann Cancer Center, Texas, USA) Prof Dr. Kevin R. Loughlin (Harvard University, Cambridge, USA) Prof. Dr. Maureen Markman (Drexel University College of Medicine, Philadelphia, USA) Prof. Dr. Stephen P. Hunger (University of Colorado School of Medicine, Colorado, USA) Prof. Dr. M.W.M. van den Brekel (Academic Medical Center Amsterdam, Amsterdam, Netherlands) Prof. Dr. M Sitki Copur (University of Nebraska Medical Center, Nebraska, USA) Prof. Dr. Derek Raghavan (UNC School of Medicine, Levine Cancer Institute, Charlotte, NC, USA) Prof. Dr. Richard J. Ablin (University of Arizona, Arizona, USA) Prof. Dr. Florian Strasser (Cantonal Hospital St. Gallen, Switzerland) Prof. Dr. Michel Rigaud (Scientific advisor - IRST, Meldola, Italy) Associate Prof. Dr. Mishu Popa McKiver (Massachusetts General Hospital, Massachusetts, USA) Assistant Prof. Dr. Alina Mihai (Univ Pittsburgh School Medicine, Pittsburgh, USA) Assistant Prof. Dr. Doru Paul (Hofstra North Shore-LIJ School of Medicine, New York, USA) Assistant Prof. Dr. Bruno Vincenzi (University Campus Bio-Medico, Rome, Italy Assistant Prof. Dr. Elizabeta C. Popa (Weill Cornell Medical College, NY, USA) Assistant Prof. Dr. Gabriela Oprea (Emory University, Atlanta, USA) Dr. Wainer Zoli (Director of the Bioscience Laboratory, IRST, Meldola, Italy) Dr. Javier Martín Broto (Son Espases Hospital, Palma de Mallorca Spain) Dr. David Gómez Almaguer (Universidad Autónoma de Nuevo León, Monterrey, México) Dr. Sankalp Yadav (General Duty Medical Officer-II, Chest Clinic Moti Nagar, North Delhi Municipal Corporation, New Delhi, India)

EDITORIAL

Lucrul în echipă – un beneficiu modern pentru pacientul oncologic Stanculeanu D.L.

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ASCO 2015 ECC 2015

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Vulvar neoplasia - synopsis and treatment trends Boiangiu A.,Vladu C., Clim N., Filipescu A.

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Hpv – silent and fearsome enemy in cervical cancer oncogenesis Penciu R., Zisu M., Tica V.

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REVIEWS

The role of urinary tract resections in advanced-stage ovarian cancer. – A Literature Review

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Obesity and breast Cancer – literature review Pantelimon I.

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Editorial

Lucrul în echipă – un beneficiu modern pentru pacientul oncologic

Dr. Dana Lucia Stănculeanu, Redactor-şef “Romanian Journal of Oncology & Hematology”

Pornind de la ierarhia valorilor umane, aproape în unanimitate, sănătatea este clasată pe primul loc. În zilele noastre, pe de o parte, pacientul este perceput ca o persoană care are o problemă de sănătate ce generează, pe lângă suferința specifică afecțiunii pe care o are, probleme psihologice și afectarea mediului social în care activează (activitatea profesională, relațiile familiale și sociale). Astfel, pacientul se află în centrul asistenței medicale de orice specialitate. Pe de altă parte, oricât de bine pregătit profesional ar fi, nici un medic nu poate să dețină toate cunoștințele și să stăpânească toate mijloacele tehnice necesare diagnosticului si tratamentului unui pacient, rezultatele cele mai bune obținându-se prin munca în echipă. Medicina modernă se bazează pe această noțiune, de muncă în echipă, de tratament interdisciplinar. Vremurile în care un pacient reprezenta doar o boală, un medic și o investigație sau operație au apus de mult, în zilele noastre, investigațiile și procedurile chirurgicale reprezentând doar o parte dintr-un lanț de proceduri diagnostice și terapeutice, al cărui scop este în final salvarea sau îmbunătățirea vieții pacientului. Consider că oncologia, poate mai mult decât orice altă specialitate medicală, cere o mare deschidere spre lucrul în echipă și colaborarea interdisciplinară între specialistul care depistează sau suspectează un caz de cancer, oncologul medical, radioterapeut, radioimagist, anatomopatolog, chirurg, psiholog si toti cei implicati in diagnostic, tratament sau urmarirea pacientului. Având pacientul în centrul preocupărilor noastre, este firesc să adunăm pentru fiecare caz în parte o echipă de specialiști din variate domenii medicale care își aduc, cu toții, contribuția la rezultatul final. Colaborarea interdisciplinară este un rezultatul firesc al specializării tot mai înalte a cadrelor medicale și duce implicit la creșterea calității actului medical, medicul specialist având capacitatea și cunoștințele necesare aplicării mijloacelor terapeutice specifice și posibilitatea însușirii informațiilor la zi privind progresele în diverse tehnici și tratamente. Terapia multimodală este un principiu modern aplicat în oncologie, ce constă în aplicarea succesivă, la un singur pacient, a mai multor metode terapeutice: chirurgie, chimioterapie, imunoterapie, radioterapie etc. Acestia alcătuiesc împreună o comisie de diagnostic si tratament, stabilind strategia terapeutică pentru fiecare caz în parte. Acest mod de colaborare duce la utilizarea optimă a fiecărei metode în beneficiul pacientului oncologic. Un vechi proverb chinezesc spune că “în spatele unui om capabil se află întotdeauna alți oameni capabili” și cred cu tărie că munca în echipă și colaborarea interdisciplinară și translațională sunt esențiale pentru a obține cele mai bune rezultate în tratamentul afecțiunilor oncologice, obiectivul final fiind viața pacientului și calitatea ei.

News

ASCO 2015

ASCO 2015: „EFFICACY AND SAFETY RESULTS FROM A PHASE III TRIAL OF NIVOLUMAB (NIVO) ALONE OR COMBINED WITH IPILIMUMAB (IPI) VERSUS IPI ALONE IN TREATMENT-NAIVE PATIENTS (PTS) WITH ADVANCED MELANOMA (MEL) (CHECKMATE 067).” -THE ASCO POST Dana Lucia Stanculeanu1, Raluca Ioana Bunghez2 1 Medic primar secția Oncologie Medicală I, Institutul Oncologic „Prof. Dr. Al. Trestioreanu” București 2Medic rezident Oncologie Medicală, Institutul Oncologic „Prof. Dr. Al. Trestioreanu” București Citation J Clin Oncol 33, 2015 (suppl; abstr LBA1), June 10, 2015, Volume 6, Issue 10 http://www.ascopost.com/issues/june-10,-2015/checkmate-067-dual-checkpoint-blockade-proveseffective-in-advanced-melanoma.aspx

Abstract

Open Access Article

In advanced melanoma, combination treatment with nivolumab (Opdivo) and ipilimumab (Yervoy) more than doubled the median progression-free survival time over ipilimumab alone in the CheckMate 067 trial. That said, single-agent nivolumab proved almost as powerful in patients expressing the programmed cell death ligand 1 (PD-L1). “Nivolumab alone and nivolumab plus ipilimumab significantly improved progression-free survival and objective response rates vs ipilimumab alone in patients with previously untreated melanoma,” Dr. Wolchok announced. “Nivolumab plus ipilimumab resulted in numerically longer progression-free survival and a higher response rate, but in patients whose tumors had at least 5% PD-L1 expression, both nivolumab alone and nivolumab/ipilimumab resulted in a similar prolongation in progression-free survival [14 months],” he reported. Dr. Wolchok concluded, “the combination represents a means to improve outcomes vs nivolumab alone, particularly for patients whose tumors have less than 5% PD-L1 expression.” (ASCO Plenary Session-Abstract LBA1)

ASCO 2015: „ELECTIVE VERSUS THERAPEUTIC NECK DISSECTION IN THE CLINICALLY NODE NEGATIVE EARLY ORAL CANCER: A RANDOMISED CONTROL TRIAL (RCT).” THE ASCO POST Citation J Clin Oncol 33, 2015 (suppl; abstr LBA3), June 25, 2015, Volume 6, Issue 11 http://www.ascopost.com/issues/june-25,-2015/elective-neck-dissection-beats-watch-and-waitapproach-in-early-oral-cancer.aspx

Abstract

Open Access Article

Elective neck dissection improved overall survival by 12.5%, reduced the risk of death by 36%, and reduced the risk of recurrence by 55% compared with therapeutic neck dissection (watch and wait approach) in the first 500 patients randomized to this trial. “Our conclusions are that elective neck dissection should be the standard of care for early node-negative squamous cell oral cancer. For every eight patients treated with elective neck dissection, one death is prevented, and for every four patients treated with elective neck dissection, one recurrence

ASCO 2015

is prevented,” stated lead author Anil K. D’Cruz, MBBS, MS, FRCS, Director, Tata Memorial Center, Head and Neck Services, Mumbai, India. Therapeutic neck dissection does not improve survival and can have associated morbidities associated with a second surgery. Performing both the primary and the neck dissection surgeries at the same time spares patients those effects. (ASCO Plenary Session-Abstract LBA3)

ASCO 2015: „REDUCTION IN LATE MORTALITY AMONG 5-YEAR SURVIVORS OF CHILDHOOD CANCER: A REPORT FROM THE CHILDHOOD CANCER SURVIVOR STUDY (CCSS)”. THE ASCO UNIVERSITY J Clin Oncol 33, 2015 (suppl; abstr LBA2), Citation http://meetinglibrary.asco.org/content/148284-156

Open Access Article

Abstract Background: Over the past four decades, treatment of many childhood cancers has been modified with the aim of achieving high survival rates while reducing the risk of life-threatening late-effects, and promoting risk-based follow-up care of survivors. Methods: Late mortality was evaluated in 34,033 5-year survivors (diagnosed < 21 years of age from 1970-1999, median follow-up 21 years, range 5-38) using cumulative incidence and Poisson regression models adjusted for demographic and disease factors to calculate relative risk (RR) and 95% confidence intervals (CI). Mortality due to non-recurrence/non-external (NR/NE) causes, which includes deaths that reflect lateeffects of cancer therapy, was evaluated. Results: 1,622 (41%) of the 3,958 deaths were attributable to NR/NE causes, including 751 subsequent neoplasm (SN), 243 cardiac, and 136 pulmonary deaths. Changes in therapy by decade included reduced rates of: cranial radiotherapy (RT) for acute lymphoblastic leukemia (ALL, 86%, 54%, 22%), RT for Wilms tumor (WT, 77%, 54%, 49%) and RT for Hodgkin lymphoma (HL, 96%, 88%, 77%). Reductions in 15 year cumulative NR/NE mortality were observed across treatment eras for ALL (p < .001), HL (p = .005), and WT (p = .005). Cardiac deaths decreased in ALL (p = .002), HL (p = .06), and WT (p = .04), and SN deaths decreased in WT (p < .001). Year of diagnosis (adjusted for age, sex, diagnosis, follow-up time) was significantly associated with a reduced risk of all-cause mortality (RR = 0.85, CI 0.83-0.87), NR/NE death (RR = 0.87, CI 0.84-0.91), death from SN (RR = 0.84, CI 0.80-0.89), cardiac death (RR = 0.78, CI 0.69-0.87) and pulmonary death (RR = 0.79, CI 0.68-0.91). Conclusions: The CCSS cohort provides evidence that the strategy of modifying therapy to reduce the occurrence of late-effects, and promotion of early detection, is successfully translating into a significant reduction in observed late mortality. (ASCO Plenary Session-Abstract LBA2)

October 2015

News

ASCO 2015

ASCO 2015: „NCCTG N0574 (ALLIANCE): A PHASE III RANDOMIZED TRIAL OF WHOLE BRAIN RADIATION THERAPY (WBRT) IN ADDITION TO RADIOSURGERY (SRS) IN PATIENTS WITH 1 TO 3 BRAIN METASTASES.” THE ASCO POST J Clin Oncol 33, 2015 (suppl; abstr LBA4), June 10, 2015, Volume 6, Issue 10 Citation http://www.ascopost.com/issues/june-10,-2015/whole-brain-radiation-risks-outweigh-benefitsfor-limited-brain-metastases.aspx

Open Access Article

Abstract The study found that although whole-brain radiation therapy improved local tumor control in patients with one to three brain metastases, but it exacerbated cognitive decline and did not improve overall survival. “Adjuvant whole-brain radiation therapy improved control of brain metastases but had no impact on survival. We saw decline in cognitive function with whole-brain radiation therapy, and quality of life was worse. We recommend treating initially with stereotactic radiosurgery and reserving whole-brain radiation therapy until the time of symptom progression,” said senior study author Jan C. Buckner, MD, of Mayo Clinic, Rochester. Studies have shown that the addition of whole-brain radiation therapy to stereotactic radiosurgery can reduce the number of patients with recurrence in treated sites and the number of new metastases. “New metastases have negative effects on cognitive function and may require additional therapy, so whole-brain radiation therapy is attractive. But on the other side, whole-brain radiation therapy carries risks. The question has been which is worse: the disease or the treatment,” Dr. Buckner continued. “A clear understanding of the risks of whole-brain radiation therapy is essential in making treatment decisions,” Dr. Brown noted at the Plenary Session. (ASCO Plenary Session-Abstract LBA4)

IMMUNOMODULATORY ACTIVITY OF NIVOLUMAB IN METASTATIC RENAL CELL CARCINOMA (MRCC): ASSOCIATION OF BIOMARKERS WITH CLINICAL OUTCOMES. THE ASCO UNIVERSITY J Clin Oncol 33, 2015 (suppl; abstr 4500) Citation http://meetinglibrary.asco.org/content/147934-156

Abstract

Open Access Article

This prospective biomarker study in patients (pts) with mRCC treated with the programmed death-1 (PD-1) inhibitor antibody nivolumab assessed baseline (BL) and changes in serum chemokines, tumor T cell infiltrates (TIL), gene expression, T cell repertoire (TCR), and other biomarkers potentially associated with clinical outcomes. Association of immune markers at BL with subsequent tumor burden response suggests that infiltrating immune activating cells may mediate response to nivolumab in mRCC pts. Consistent with the randomized phase II study of nivolumab in mRCC, OS appears longer in PD-L1+ pts but promising in both PD-L1+ and PD-L1– pts, especially when treatment-naive. (ASCO 2015 Oral Abstract Session, Genitourinary (Nonprostate) Cancer, Abstract 4500)

ASCO 2015

ASCO 2015 „PHASE III, RANDOMIZED TRIAL (CHECKMATE 057) OF NIVOLUMAB (NIVO) VERSUS DOCETAXEL (DOC) IN ADVANCED NON-SQUAMOUS CELL (NON-SQ) NON-SMALL CELL LUNG CANCER (NSCLC)”. THE ASCO POST Citation J Clin Oncol 33, 2015 (suppl; abstr LBA10), June 10, 2015, Volume 6, Issue 10 http://www.ascopost.com/issues/june-10,-2015/second-line-nivolumab-therapy-improvessurvival-in-patients-with-nonsquamous-non-small-cell-lung-cancer.aspx

Open Access Article

Abstract Dr Paz-Ares reported the results of the phase III CheckMate 057 trial at a press conference during the 2015 ASCO Annual Meeting. Anti–programmed cell death protein 1 (PD-1) immunotherapy with nivolumab (Opdivo) extended survival in patients with the most common form of lung cancer—nonsquamous non–small cell lung cancer (NSCLC). Patients whose disease progressed on standard platinum doublet therapy who were treated with nivolumab lived an average of 3 months longer than those treated with docetaxel in this setting. “Nivolumab is the first PD-1 inhibitor to significantly improve overall survival vs docetaxel in previously treated patients with advanced nonsquamous NSCLC. Nivolumab appears to be particularly active in patients with PD-1 ligand (PD-L1)–positive tumors. Nivolumab significantly improved response rates, with objective response rates as high as 36% in PD-L1 expressors. Overall survival approximately doubled with nivolumab vs docetaxel across the PD-L1–expressing continuum,” said Luis Paz-Ares, MD, PhD. In the subgroup of patients with the highest level of PD-L1 expression (≥ 10% of cells), median overall survival with nivolumab was 19 months, compared with 8 months for those treated with docetaxel. Median overall survival was also substantially higher with nivolumab compared with docetaxel in those with PD-L1 ≥ 5% and ≥ 1%. “These results suggest that PD-L1 expression is predictive of the survival benefit of nivolumab, with a huge benefit observed in those with positive expression: a 41% to 60% reduction in the risk of death, which was not found in patients with low or undetectable PD-L1 levels,” Dr. Paz-Ares noted. No difference in median overall survival was observed between the two treatment arms in those with low PD-L1 expression (< 10% of cells). Safety results were reassuring, Dr. Schuchter commented. “Toxicities can be immune-related, and immunotherapies have unique toxicities,” she continued. “In this study, the immune-related adverse events were less severe than those seen with chemotherapy.” (ASCO 2015 Clinical Science Symposium, Immunotherapy for Every Patient: Check Your Enthusiasm, -Abstract LBA10)

October 2015

News

ASCO 2015

ANTITUMOR ACTIVITY AND SAFETY OF PEMBROLIZUMAB IN PATIENTS (PTS) WITH ADVANCED SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK (SCCHN): PRELIMINARY RESULTS FROM KEYNOTE-012 EXPANSION COHORT. THE ASCO POST Citation J Clin Oncol 33, 2015 (suppl; abstr LBA6008), June 10, 2015, Volume 6, Issue 10 http://www.ascopost.com/issues/june-10,-2015/clinically-meaningful-preliminary-resultswith-pembrolizumab-in-recurrent-head-and-neck-cancer.aspx

Open Access Article

Abstract Pembrolizumab (Keytruda) has encouraging results in heavily pre-treated patients with recurrent or metastatic squamous cell carcinoma of the head and neck, according to a report on the expansion-cohort KEYNOTE-012 study presented at the 2015 ASCO Annual Meeting. “The efficacy we saw was remarkable. This is the largest experience with immunotherapy in head and neck cancer. Pembrolizumab was roughly twice as effective when measured by response as we have seen with cetuximab [Erbitux], our only approved targeted therapy for head and neck cancer. Responses are durable, which has not been seen before in head and neck cancer and pembrolizumab seems to be broadly active regardless of HPV status, PD-L1 status, or prior treatment,” said lead author Tanguy Y. Seiwert, MD, Assistant Professor of Medicine and Associate Program Leader for Head and Neck Cancer at the University of Chicago. Pembrolizumab is the first anti–programmed cell death protein 1 (PD-1) therapy to be approved by the U.S. Food and Drug Administration. It is approved in advanced melanoma and is now being studied in other solid tumors. This expansion cohort enrolled 132 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, irrespective of PD-L1 or HPV status. All patients received fixed-dose pembrolizumab (infusion of 200 mg every 3 weeks) for 24 months or until disease progression or intolerable toxicity. About 59% had been previously treated with two or more therapies for recurrent or metastatic head and neck cancer. Tumor shrinkage was reported in 56%. The overall objective response rate was 24.8%: 27.2% in HPV-negative patients and 20.6% in HPV-positive patients. About 25% of patients had stable disease, for a disease control rate of about 50%, which Dr. Seiwert called “very promising” as many patients with prolonged stable disease may ultimately also benefit from immunotherapy, Dr. Seiwert said. “Pembrolizumab was well tolerated, better than with chemotherapy or radiation,” Dr. Seiwert said. About 60% of patients had any adverse events, but were mostly mild: 15% had mild, low grade (grade 1/2) side effects included hypothyroidism (9.1%), decreased appetite (7.6%), and rash (7.6%). Furthermore, it may be possible to predict who is most likely to benefit from pembrolizumab using PD-L1 as a biomarker, Dr. Seiwart noted. Analysis of PD-L1 status and response is ongoing. (ASCO 2015 Oral Abstract Session, Head and Neck Cancer, Abstract LBA6008)

ASCO 2015

RANDOMIZED, OPEN-LABEL, MULTICENTER, PHASE III STUDY OF ERIBULIN VERSUS DACARBAZINE IN PATIENTS (PTS) WITH LEIOMYOSARCOMA (LMS) AND ADIPOCYTIC SARCOMA (ADI). THE ASCO POST Citation J Clin Oncol 33, 2015 (suppl; abstr LBA10502), June 25, 2015, Volume 6, Issue 11 http://www.ascopost.com/issues/june-25,-2015/eribulin-improves-overall-survival-in-difficultto-treat-sarcoma-types.aspx

Open Access Article

Abstract Eribulin is a microtubule inhibitor that blocks cell division. In preclinical models, it also has been shown to impact tumor cells via vascular remodeling, reversal of epithelial-mesenchymal transition, as well as suppression of migration and invasion. In the global phase III study (Study 309), eribulin reduced the risk of death by 23%, compared with dacarbazine, in patients with advanced liposarcomas and leiomyosarcomas, reported Patrick SchÖffski, MD, of University Hospitals Leuven in Belgium. “The study’s primary endpoint of overall survival— a very reliable endpoint—was met. Eribulin had a favorable median survival of 13.5 months, vs the standard agent dacarbazine, 11.5 months (hazard ratio = 0.768; P = .0169).” Secondary endpoints, however, were not significantly different. Median progression-free survival was 2.6 months in both arms. The progression-free survival rate at 12 weeks was 33% for the eribulin arm and 29% for the dacarbazine arm. Gary K. Schwartz, MD, noted, “There’s never been a randomized study of this type showing a survival benefit in advanced sarcoma in the history of medical oncology. It’s a small step forward in oncology but a major step for sarcoma patients.” (ASCO 2015 Oral Abstract Session, Sarcoma Abstract LBA10502)

PALOMA3: A DOUBLE-BLIND, PHASE III TRIAL OF FULVESTRANT WITH OR WITHOUT PALBOCICLIB IN PRE- AND POST-MENOPAUSAL WOMEN WITH HORMONE RECEPTOR-POSITIVE, HER2-NEGATIVE METASTATIC BREAST CANCER THAT PROGRESSED ON PRIOR ENDOCRINE THERAPY. THE ASCO POST J Clin Oncol 33, 2015 (suppl; abstr LBA502), June 25, 2015, Volume 6, Issue 11 Citation http://www.ascopost.com/issues/june-25,-2015/palbociclib-slows-progression-ofhormone-receptor-positive-breast-cancer.aspx

Abstract

Open Access Article

PALOMA3 enrolled 521 premenopausal or postmenopausal women who had progressed on prior endocrine therapy and had no more than one prior treatment for advanced cancer. They were randomized 2:1 to the combination arm (n = 347), which was palbociclib (125 mg/d for 3 weeks on, 1 week off) plus fulvestrant (500 mg) every 4 weeks, or fulvestrant plus placebo (n = 174). The primary endpoint was investigator-assessed progression-free survival. At the time of the preplanned interim analysis, median progression-free survival was 9.2 months in the palbociclib/fulvestrant arm and 3.8 months in the placebo arm, producing a highly significant hazard ratio of 0.422 (P < .000001). Asked by The ASCO Post how this October 2015

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ASCO 2015

doublet compares with everolimus (Afinitor) plus exemestane, Dr. Turner commented, “Palbociclib more than doubled the progression-free survival in this study, but importantly, it was very well tolerated. Very few patients had to stop because of side effects, and that will be key as palbociclib moves forward.” He also explained the choice of fulvestrant as the endocrine therapy. “We are identifying in hormone receptor–positive breast cancer that CDK4/6 is a key gene allowing these cancers to proliferate. This study confirms that as breast cancers become resistant to endocrine therapy, CDK4/6 is still a target, and palbociclib is still very active. It’s a standard hormone therapy and is likely the most active one. We have significant laboratory data showing synergy between palbociclib and fulvestrant in two cell line models of endocrine resistance.” “This phase III trial identifies and confirms CDK4/6 as a key target for hormone receptor–positive breast cancer,” Dr. Turner commented at a press briefing. (ASCO 2015 Oral Abstract Session, Breast Cancer—HER2/ER, Abstract LBA502)

A PHASE III PROTOCOL OF ANDROGEN SUPPRESSION (AS) AND 3DCRT/IMRT VERSUS AS AND 3DCRT/IMRT FOLLOWED BY CHEMOTHERAPY (CT) WITH DOCETAXEL AND PREDNISONE FOR LOCALIZED, HIGH-RISK PROSTATE CANCER (RTOG 0521). THE ASCO POST Citation J Clin Oncol 33, 2015 (suppl; abstr LBA5002), June 10, 2015, Volume 6, Issue 10 http://www.ascopost.com/issues/june-25,-2015/adjuvant-chemotherapy-proves-effectivein-localized,-high-risk-prostate-cancer.aspx

Open Access Article

Abstract “This is the first study to demonstrate a survival benefit for high-risk localized prostate cancer with chemotherapy as adjuvant therapy plus androgen-deprivation therapy and radiation. The follow-up is relatively short, but there is significant separation of the survival curves at 5 to 6 years, and we would expect that to continue with longer follow-up. This is treatment with curative intent.” Said Dr. Ryan, Clinical Program Leader for Genitourinary Medical Oncology at the University of California San Francisco, Helen Diller Family Comprehensive Cancer Center. Patients included in the trial had Gleason scores between 8 and 10, prostate-specific antigen (PSA) ≥ 20 ng/mL, or ≥ T2 stage. The median age was 66 years. The median PSA level was 15.1 ng/mL; 53% had Gleason scores of between 9 and 10; 31% had a Gleason score of 8; 16% had a Gleason score of 7; and 33% had node-negative disease. At a median follow-up of 5.5 years, 4-year overall survival was 89% in arm 1 and 93% with docetaxel, for an absolute benefit of 4% (one-sided P value of .04). This represented a 30% reduction in risk of death favoring adjuvant docetaxel. Docetaxel also achieved a reduction in distant metastases at any time during the trial compared with androgen suppression and radiotherapy alone; 41 events were observed in arm 1 and 26, in arm 2. The risk of biochemical failure was reduced by 20% in the docetaxel-containing arm. Adverse events were as expected, with more grade 3 and 4 hematologic toxicity in the docetaxel arm. The investigators stressed that longer follow-up is needed to determine whether such therapy also improves metastasis-free or overall survival. (ASCO 2015 Oral Abstract Session, Genitourinary (Prostate) Cancer, Abstract LBA5002)

ECC 2015

NEWS IN BREAST CANCER ECC 2015 „OVARIAN SUPPRESSION WITH LUTEINIZING HORMONE-RELEASING HORMONE AGONISTS DURING CHEMOTHERAPY AS A STRATEGY TO PRESERVE OVARIAN FUNCTION AND FERTILITY IN BREAST CANCER PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED STUDIES”

Dana Lucia Stanculeanu1, Raluca Ioana Bunghez2 1 Medic primar secția Oncologie Medicală I, Institutul Oncologic „Prof. Dr. Al. Trestioreanu” București 2Medic rezident Oncologie Medicală, Institutul Oncologic „Prof. Dr. Al. Trestioreanu” București

1 Citation Abstract number: 1957, , M. Lambertini, Italy. P146 - Monday 28th September 2015 – 09:1511:15 Poster Session HALL C, Abstract at ECC 2015, held 25–29 September in Vienna, Austria; 2 Moore HCF et al, 2015. Ovarian protection during adjuvant chemotherapy. N Engl J Med; 372(23):2269–70. (link: http://www.esmo.org/Conferences/European-Cancer-Congress-2015/News/Preserving-fertility-inbreast-cancer-patients-new-promises) ECC 2015-Poster Session-Breast Cancer , Abstract number: 1957, by Matteo Lambertini et al. Annals of Oncology. doi:10.1093/annonc/mdv374

Open Access Article

Abstract Meta-analiza prezentata a evidentiat ca suprimarea temporara functiei ovariene cu agonist LH-RH reduce semnificativ riscul insuficientei ovariane induse de chimioterapie si pare a fi asociat cu o rata mai mare a sarcinilor in cazul pacientelor tinere cu cancer de san. Rolul inhibitiei ovariane cu agonisti LH-RH in prevenirea insuficientei ovariene premature induse de chimioterapie (POF) este inca controversata. Noi date prezentate la ECC 2015 sugereaza eficacitatea administrarii agonistilor LH-RH pentru pastrarea functiei ovariane la pacientele cu cancer de san. Meta-analiza prezentata si-a propus sa investigheze daca utilizarea LH-RHa in timpul chimioterapiei la pacientele cu cancer de san in premenopauza ar reduce rata insuficientei ovariene legate de tratamentul citostatic si daca se observa o crestere a ratei sarcinilor ulterioare. Un total de 12 studii clinice randomizate au fost eligibile si au inclus 1.231 de paciente cu cancer de san. In cadrul studiilor s-au utilizat diferite definitii ale insuficientei ovariene (amenoree cu sau fara nivel hormonal dozat) si au cuprins evaluari la 6, 8, 12, 24 sau 36 luni. Analiza a fost restrictionata la 8 studii cu informatii disponibile cu privire la rata amenoreei la un an dupa terminarea chimioterapiei. Adaugarea agonistului LH-RH a confirmat existenta unui efect benefic (OR = 0.55; 95% CI 0.41-0.73, p <0.001), cu nici o heterogenitate semnificativa intre studii (I pătrat = 0.0%, p = 0.936). Cinci dintre studii au raportat numarul de sarcini aparute dupa terminarea tratamentului citostatic: 33 de sarcini au aparut la pacientele la care s-a administrat concomitent chimioterapie cu agonist LH-RH si 19 sarcini in cazul pacientelor care au urmat doar chimioterapie (OR = 1,83; 95% CI 1.02-3.28, p = 0,041). 1Dr Lambertini declara “Major international guidelines from ASCO and ESMO consider the administration of LHRHa during chemotherapy an experimental strategy to preserve ovarian function and fertility. This is mainly because of the lack of data on long-term ovarian function and pregnancies. However, these guidelines were published before two of the larger studies became available, the POEMS-SWOG S0230 trial[3] and the updated results of the PROMISE-GIM6 study[4].” Trialurile POEMS-SWOG S0230 si PROMISE-GIM6 au analizat intervalul liber de boala (disease-free survival) dupa terminarea tratamentului citostatic. Studiul POEMS-SWOG S0230, care a inclus paciente cu receptori hormonali negativi a evidentiat o crestere a DFS daca au primit agonist LH-RH concomitent cu tratamentul citostatic. Rezultatele studiului PROMISEGIM6 au aratat ca nu exista nicio diferenta privind supravietuirea, chiar si in subgrupul pacientelor cu receptori hormonali prezenti (majoritatea pacientelor inrolate in studiu). October 2015

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ECC 2015

Pana in prezent aceasta abordare in conservarea fertilitatii ramane controversata, dar noile date sugereaza ca utilizarea inhibitiei ovariene poate fi utila si realizata in conditii de siguranta atat in cazul pacientelor cu neoplasm mamar cu receptori negativi, cat si in cazul celor cu receptori hormonali pozitivi, ce reprezinta majoritatea in cazul femeilor tinere recent diagnosticate cu neoplasm mamar.1,2

„PRELIMINARY SAFETY RESULTS FROM PERUSE, A STUDY OF 1436 PATIENTS (PTS) TREATED WITH FIRST-LINE PERTUZUMAB (P) COMBINED WITH TRASTUZUMAB (H) AND TAXANE THERAPY FOR HER2-POSITIVE LOCALLY RECURRENT/ METASTATIC BREAST CANCER (LR/MBC)” 1 Abstract number: 1816, D. Miles, UK. Monday 28th September 2015 – 08:00-09:00 Citation Poster Discussion Session HALL D1, Abstract presented at ECC 2015, held 25–29 September in Vienna, Austria; 2 Baselga J, Cortés J, Kim SB, et al: Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 366:109-119, 2012. http://www.esmo.org/Conferences/European-Cancer-Congress-2015/News/Preliminary-Results-fromPERUSE-Study-Increase-Treatment-Options-in-HER-Positive-Patients-with-Metastatic-Breast-Cancer

ECC 2015-Poster Session-Breast Cancer , Abstract number: 1816, by D. Miles et al.

Abstract

Open Access Article

Rezultatele preliminare ale studiului PERUSE prezentate la ECC 2015 din Viena aduc in discutie utilizarea paclitaxelului si nab-paclitaxelului in cazul pacientelor cu cancer mamar metastatic, HER2-pozitiv. Pornind de studiul de faza III CLEOPATRA ce a demonstrat rezultate superioare privind intervalul liber de boala si supravietuirea globala la adaugarea pertuzumabului in prima linie alaturi de herceptin + docetaxel la pacientele cu cancer de san metastatic, HER2-pozitiv, s-a pus problema inlocuirii docetaxelului cu paclitaxel, putine date existand despre combinatia pertuzumab + herceptin + paclitaxel / nab-paclitaxel. 1,2 Studiul multicentric de faza IIIb PERUSE compara administrarea in prima linie a pertuzumab + herceptin + paclitaxel / nab-paclitaxel si pertuzumab + herceptin + docetaxel in cazul pacientelor cu cancer de san metastatic/recidivat loco-regional, HER2-pozitiv. Rezultatele preliminare au relevat date despre siguranta, incidenta si severitatea reactiilor adverse si afectarea cardiaca. Efectul secundar comun administrarii de pertuzumab / trastuzumab a fost diareea, care a fost observata in cazul tuturor celor trei tipuri de taxani. In cazul docetaxelului au fost raportate mai multe cazuri de mucozita, toxicitate hematologica și neutropenie febrila decat in randul pacientelor care au primit nab-paclitaxel si paclitaxel. Acestea din urma au dus mai frecvent la aparitia neuropatiei periferice. Privind afectarea cardiaca nu au existat diferente importante care sa sugereze o deterioarea a functiei cardiace mai mare fata de administrarea pertuzumab + herceptin + docetaxel. Date privind eficacitatea tratamentului inca nu sunt disponibile, studiul PERUSE confirmand pentru moment siguranta si tolerabilitatea utilizarii altor taxani, exceptand docetaxelul, alaturi de pertuzumab + herceptin.1.2

ECC 2015

„FINAL RESULTS FOR OVERALL SURVIVAL (OS), THE PRIMARY ENDPOINT OF THE CECOG TURANDOT PROSPECTIVE RANDOMISED TRIAL EVALUATING BEVACIZUMAB-PACLITAXEL (BEV-PAC) VS BEV-CAPECITABINE (CAP) FOR HER2-NEGATIVE LOCALLY RECURRENT/METASTATIC BREAST CANCER (LR/MBC)” Dana Lucia Stanculeanu1, Raluca Ioana Bunghez2 1 Medic primar secția Oncologie Medicală I, Institutul Oncologic „Prof. Dr. Al. Trestioreanu” București 2Medic rezident Oncologie Medicală, Institutul Oncologic „Prof. Dr. Al. Trestioreanu” București 1 Citation Abstract number: 1800, C.C. Zielinski et al, Vienna, Austria. Monday 26th September 2015 – Proffered Paper Session HALL D1, Abstract presented at ECC 2015, held 25–29 September in Vienna, Austria http://www.esmo.org/Conferences/European-Cancer-Congress-2015/News/TURANDOT-First-Line-Bevacizumab-Plus-Capecitabine-Shows-Non-Inferior-Overall-Survival-versus-Bevacizumab-plus-Paclitaxel-forMetastatic-Breast-Cancer ECC 2015-Proffered Paper Session-Breast Cancer , Abstract number: 1800, by C.C. Zielinski et al.

Open Access Article

Abstract Studiul de faza III TURANDOT (NCT00600340) compara administrarea in prima linie a bevacizumab+capecitabina vs bevacizumab plus paclitaxel in cazul celor 564 de paciente inrolate cu neoplasm mamar, recidivat loco-regional/metastatic, HER2-negativ. Obiectivul studiului a fost de a demonstra non-inferioritatea in privinta supravietuirii globale intre cele doua asocieri. Pacientele au fost randomizate sa primeasca in prima linie bevacizumab plus paclitaxel (i.v. bevacizumab 10 mg/kg- ziua 1 si 15 plus i.v. paclitaxel 90 mg/m2 in ziua 1, 8 and 15, repetat la 4 saptamani; n=285) sau bevacizumab+capecitabina (i.v. bevacizumab 15 mg/kg-ziua 1 plus capecitabina oral 1000 mg/m2 x 2/zi ziua 1–14, repetat la 3 saptamani; n=279), pana la progresia bolii sau toxicitate importanta. Stratificarea s-a efectuat in functie de origine, statusul menopauzal si prezenta receptorilor hormanali (ER/PGR). Studiul a demonstrat non-inferioritate in privinta supravietuirii globale (obiectiv primar) a bevacizumab / capecitabina, comparativ cu bevacizumab / paclitaxel în analiza primara (analiza stratificata in populația per-protocol (PP)). Cu toate acestea, rezultatele analizelor de sensibilitate nestratificata au fost în contradictie cu rezultatele primare, urmand ca autorii sa exploreze acesta incoerenta, precum si heterogenitatea dintre subgrupuri. In privinta PFS-ului (obiectiv secundar) a avut rezultate semnificativ superioare bratul cu bevacizumab / paclitaxel comparativ cu bevacizumab / capecitabina. Pe baza constatarilor studiului TURANDOT, selectarea unui anumit regim continand bevacizumab ar trebui luata in considerare in functie de multi factori, inclusiv de particularitatile fiecarui pacient.1

October 2015

Original article

Radical gastrectomy with para-aortic lymph node dissection for non-Hodgkin gastric lymphoma –a case report

RADICAL GASTRECTOMY WITH PARA-AORTIC LYMPH NODE DISSECTION FOR NON-HODGKIN GASTRIC LYMPHOMA – A CASE REPORT Nicolae Bacalbasa1, Irina Balescu2 “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania 2 “Ponderas” Hospital, Bucharest, Romania Corresponding author: Nicolae Bacalbașa, Adress: Dimitrie Racoviță Street, no. 2, Bucharest, Romania E-mail: nicolae_bacalbasa@yahoo.ro Phone no: +40723540426

Open Access Article

Abstract Keywords: non-Hodgkin gastric lymphoma, chemotherapy, radical surgery

Gastric lymphoma is a rare condition which can be treated by neoadjuvant chemotherapy followed by surgery or chemotherapy alone. However in some cases in which patients develop severe complications during chemotherapy, surgery remains the only option of choice. We present the case of a 62 year old patient diagnosed with small cell non-Hodgkin lymphoma, who developed a severe gastric bleeding during chemotherapy so she was submitted to surgery. A total gastrectomy with para-ortic lymph node dissection was performed with good outcomes.

Introduction

Received: October 2015 Reviewed: October 2015 Accepted: October 2015

Cite this article: Bacalbasa N., Balescu I. Radical gastrectomy with para-aortic lymph node dissection for non-Hodgkin gastric lymphoma–a case report Rom J Oncol Hematol. 2015; 7(2):86-88

Gastric non-Hodgkin lymphoma is a rare condition accounting for up to 5 % of all gastric malignancies for which no therapeutic consensus exists (1,2). In the mean time, the stomach is the most common extranodal involvement of non-Hodgkin lymphoma (3-5). When it comes to long term outcomes, gastric lymphoma is associated with an improved outcome when compared to other gastric malignancies including gastric adenocarcinoma (6-8) and many therapeutic strategies have been proposed; An well established consensus has not yet been obtained (1). Nowadays large studies opiniate for CHOP regimen chemotherapy as first line therapy; however it is not possible in all cases due to the development of local complications (1). Case report A 62 year old patient was initially investigated for an upper digestive hemmorhage after previous administration of non-steroidian anti-inflammatory treatment one week earlier. The upper digestive fibroscopy revealed multiple ulcerated tumors developed on the greater curvature of the stomach with a high suspicion of malignancy. The biopsy indicated the presence of diffuse lymphoid infiltration involving the muscularis mucosae with high suspicion of lymphoma. The immunohistochemi-

Figure 1. The initial aspect: the stomach is

infiltrated on the whole length of the greater curvature cal studies revealed the presence of CD20, the absence of CD3, the presence of diffuse positive Kappa and rarely positive Lambda, Kappa/Lambda =6/1, while Ki67 was positive in 2% of all tumor cells, sustaining the idea of the presence of a small cell non-Hodgkin malignant lymphoma. The whole body MRI performed indicated the presence of a large gastric tumor invading the upper part of the

Bacalbasa N., Balescu I.

Figure 2. The left gastric artery is ligated at itsâ&#x20AC;&#x2122;

origin greater curvature associated with the presence of multiple enlarged lymph nodes in the peri-gastric and para-aortic lymph node stations. The patient was submitted to chemotherapy with CHOP regimen, but during the third cycle she developed a severe bleeding with haemorrhagic shock, so she was addressed in emergency to Visceral Surgery service. A total gastrectomy with para-aortic lymph node dissection was performed with good outcomes, the patient being discharged in the 8th postoperative day (Fig 1-5). The macroscopic aspect of the specimen showed the presence of multiple ulcerated tumors, enabling us to consider that a partial remission of the tumor was achieved under chemotherapy. However in this certain case the rapid degradation of the general biological status due to the apparition of a severe upper digestive haemorrhage imposed an emergency laparotomy in order to perform a resection with haemostatic purpose. Discussions Malignant lymphoma of the gastrointestinal tract represent up to 15% of all lymphoma, the stomach being by far the most commonly involoved gastrointestinal site (1,2,9,10). Usually these proliferative diseases originate in the lymphoid viscera or in other sites and have a significant number of lymphoid cells; less common, they can develop in sites which do not have a well represented lymphoid tissues such as the stomach. The most frequent symptoms at diagnosis include abdominal pain, hematemesis and weight loss, hence it is difficult to differentiate it from other malignant conditions such as adenocarcinoma (11). The initial aspect during upper endoscopy is similar to an ulceration with extensive gastric wall involvement, gastric fibroscopy being able to provide the positive diagnosis in 75-90% of cases (1,12,13). In order to have a positive diagnosis of gastric lymphoma and to establish the histopatho-

Figure 3. Lymph node dissection at the level of

the hepatic pedicle logical subtype, immunohistochemistry is needed. The basic immunohistochemical panel includes antibodies against B-cell (CD20) and T-cell (CD3) antigens and light chains determination in cases presenting numerous plasma cells; the presence of CD45, CD15, and CD30 should be tested if large dysplastic cells are seen. Based on the morphology, cases presenting alteration of B-cell areas, antibodies against CD5, CD10, CD23, CD43, B-cell lymphoma 2 protein (BCL-2), and B-cell lymphoma 6 protein (BCL- 6) would also be useful to further characterize the process. Testing the presence of kappa and lambda light chains may help to identify the presence of an abnormal clonal population, particularly plasma cells. However, immunohistochemistry is less sensitive than flow cytometry for the detection of immunoglobulin expression, as it does not detect the surface immunoglobulin (14). Once the positive diagnosis of non Hodgkin gastric lymphoma is achieved, the most effective therapeutical strategy remains a matter of debate. Initially it has been considered that total or partial gastrectomy is the first therapeutic option (15,16). The rationale for this option consisted in providing a complete tumor removal and an adequate staging; it could also diminish the rates of chemotherapy administration which was taught to have unacceptable risks of hemorrhagy and tumor perforation (1). However, more recent studies demonstrated that the postoperative complications after gastrectomy are also significant, with a mortality rate of up to 18%, while the overall survival is not significantly improved in cases treated by surgery when compared to those submitted to chemotherapy (5,17). When it comes to the most important prognostic factors influencing the long term outcomes, it has been widely demonstrated that the cellular type and the stage significantly impact on survival. Musshoff et al modificated Ann Arbor classificiation and separated the cases included in stage II of the disease into cases with local nodal inOctober 2015

Original article

Radical gastrectomy with para-aortic lymph node dissection for non-Hodgkin gastric lymphoma –a case report

Figure 4. The final aspect after para-aortic lymph

Figure 5. The specimen presenting large

node dissection

infiltrative zones with haemorrhagic stigmata

volvement (II1) and cases with more distant spread to para-aortic nodes (II2); they demonstrated that patients with stage II2 disease have a significantly worse prognosis than those with stage II1 disease (18).

tions of oncological treatment and to improve the long term outcome.

Conclusions

This work received financial support through the project entitled “CERO – Career profile: Romanian Researcher”, grant number POSDRU/159/1.5/S/135760, cofinanced by the European Social Fund for Sectoral Operational Programme Human Resources Development 2007-2013.

Although large studies could not clearly demonstrate the effectiveness of surgery followed by chemotherapy when compared to chemotherapy only for gastric lymphoma, there are cases in which surgery is the only potential curative solution due to the significant chemotherapy related complications which might develop. In our case, total gastrectomy with lymph node dissection seemed the best therapeutic protocol in order to minimise the complica-

Acknowledgement:

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References 1. Ho CL, Hsieh AT, Dai MS, Chen YC, Kao WY, Chao TY. Non-Hodgkin’s lymphoma of the stomach: treatment outcomes for 57 patients over a 20year period. J Chin Med Assoc 2005; 68(1):11-15. 2. Nakamura S, Matsumoto T, Iida M, Yao T, Tsuneyoshi M. Primary gastrointestinal lymphoma in Japan: a clinicopathologic analysis of 455 patients with special reference to its time trends. Cancer 2003; 97(10):2462-2473. 3. Hockey MS, Powell J, Crocker J, Fielding JW. Primary gastric lymphoma. Br J Surg 1987; 74(6):483-487. 4. Dworkin B, Lightdale CJ, Weingrad DN, DeCosse JJ, Lieberman P, Filippa DA et al. Primary gastric lymphoma. A review of 50 cases. Dig Dis Sci 1982; 27(11):986-992. 5. Dragosics B, Bauer P, Radaszkiewicz T. Primary gastrointestinal nonHodgkin’s lymphomas. A retrospective clinicopathologic study of 150 cases. Cancer 1985; 55(5):1060-1073. 6. Krugmann J, Dirnhofer S, Gschwendtner A, Berresheim U, Greil R, Krugmann K et al. Primary gastrointestinal B-cell lymphoma. A clincopathological and immunohistochemical study of 61 cases with an evaluation of prognostic parameters. Pathol Res Pract 2001; 197(6):385393. 7. Pandey M, Wadhwa MK, Patel HP, Kothari KC, Shah M, Patel DD. Malignant lymphoma of the gastrointestinal tract. Eur J Surg Oncol 1999; 25(2):164167. 8. Ohtsu A. The latest advances in chemotherapy for gastrointestinal cancers. Int J Clin Oncol 2003; 8(4):234-238. 9. d’Amore F, Brincker H, Gronbaek K, Thorling K, Pedersen M, Jensen MK et al. Non-Hodgkin’s lymphoma of the gastrointestinal tract: a populationbased analysis of incidence, geographic distribution, clinicopathologic presentation features, and prognosis. Danish Lymphoma Study Group. J

Clin Oncol 1994; 12(8):1673-1684. 10. Arenas R. Gastric lymphoma. In: Posner M, Vokes E, Weichselbaum R eds. Cancer of the Upper Gastrointestinal Tract. London: BC Decker, Inc 2002: 322-335 11. Al Akwaa AM, Siddiqui N, Al Mofleh IA. Primary gastric lymphoma. World J Gastroenterol 2004; 10(1):5-11. 12. Ben Yosef R, Hoppe RT. Treatment of early-stage gastric lymphoma. J Surg Oncol 1994; 57(2):78-86. 13. Maor MH, Maddux B, Osborne BM, Fuller LM, Sullivan JA, Nelson RS et al. Stages IE and IIE non-Hodgkin’s lymphomas of the stomach. Comparison of treatment modalities. Cancer 1984; 54(11):2330-2337. 14.Higgins RA, Blankenship JE, Kinney MC. Application of immunohistochemistry in the diagnosis of non-Hodgkin and Hodgkin lymphoma. Arch Pathol Lab Med 2008; 132(3):441-461. 15. Gobbi PG, Dionigi P, Barbieri F, Corbella F, Bertoloni D, Grignani G et al. The role of surgery in the multimodal treatment of primary gastric nonHodgkin’s lymphomas. A report of 76 cases and review of the literature. Cancer 1990; 65(11):2528-2536. 16. Shchepotin IB, Evans SR, Shabahang M, Chorny V, Buras RR, Korobko V et al. Primary non-Hodgkin’s lymphoma of the stomach: three radical modalities of treatment in 75 patients. Ann Surg Oncol 1996; 3(3):277284. 17. Romagurea JE, Velasquez WS, Silvermintz KB, Fuller LB, Hagemeister FB, McLaughlin P et al. Surgical debulking is associated with improved survival in stage I-II diffuse large cell lymphoma. Cancer 1990; 66(2):267272. 18. Musshoff K, Schmidt-Vollmer H. Proceedings: Prognosis of nonHodgkin’s lymphomas with special emphasis on the staging classification. Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 1975; 83(4):323-341.

October 2015

Original article

Vulvar neoplasia - synopsis and treatment trends

VULVAR NEOPLASIA - SYNOPSIS AND TREATMENT TRENDS Andreea Boiangiu1, Cristina Vladu1, Nicoleta Clim1, Alexandru Filipescu1,2 1. Department of Obstetrics and Gynecology – University Hospital ELIAS, Bucharest; 2. University Of Medicine and Pharmacy “Carol Davila”, Bucharest Corresponding author: Andreea Boiangiu, andreeaboiangiu@gmail.com

Abstract Keywords: vulvar carcinoma, tumor, HPV infection

Vulvar carcinoma is a rare, uncommon tumor representing about 4% from all gynecological malignancies. Although etiological agents are controversial two independent pathways of vulvar carcinogenesis currently exist, the first related to mucosal HPV infection and the second related to chronic inflammatory (vulvar dystrophy) or autoimmune processes . Squamous carcinoma of the vulva usually proceeds in a predictable fashion through its regional lymphatics, first to the inguinal-femoral nodes and only then to pelvic and distant sites. One of the most important recent developments in the treatment of vulvar carcinoma has been the individualization of treatment with less radical surgery for early stage disease.

Introduction:

Received: October 2015 Reviewed: October 2015 Accepted: October 2015

Vulvar carcinoma is a rare, uncommon tumor representing about 4% from all gynecological malignancies. Postmenopausal womans are predominately affected in the 6th and 7th decade[1]. Histopathological approximately 95% of malignant tumors of the vulva are scuamos cells carcinomas, but melanomas, adenocarcinomas, sarcomas and other malignant forms are also described. The worldwide reported incidence is 1–2 per 100 000 women. Labia majora and labia minora are the most common sites were vulvar neoplasia occurs, but it can also apear on the perineum and clitoris. The majority of vulvar SCC are solitary. However, multifocal tumors are seen in 10% of cases. SCC may appear as an exophytic or an endophytic ulcerated lesion[2].

Risk factors

Risk factors for vulvar cancer include cigarette smoking, vulvar dystrophy (eg, lichen sclerosus), human papillomavirus (HPV) infection, immunodeficiency syndromes, a prior history of cervical cancer and northern European ancestry [3,4]. Although etiological agents are controversial, two independent pathways of vulvar carcinogenesis currently Cite this article: exist. The first is related to mucosal HPV infection Boiangiu A.,Vladu C., Clim N., Filipescu A. and the second is related to chronic inflammatory Vulvar neoplasia (vulvar dystrophy) or autoimmune processes [5]. synopsis and treatment HPV has been shown to be responsible for 60 pertrends [6] Rom J Oncol Hematol. cent of vulvar cancers . Specifically, HPV 16 and 33 are the predominant subtypes accounting for 2015; 7(2):90-93

Figure 1. Vulvar midline lesions

55.5 percent of all HPV-related vulvar cancers [7]. Carter et al. have observed the occurrence of invasive vulvar cancer also in younger premenopausal patients, with a trend for multifocal lesions associated with vulvar intraepithelial neoplasia (VIN) and these lesions are associated with human papillomavirus (HPV) infections. HPV DNA is found more commonly in vulvar cancers of young women who smoke as compared with older nonsmokers[6]. Early detection and treatment of vulvar intraepithelial neoplasia may prevent the development

Boiangiu A., Vladu C., Clim N., Filipescu A.

Table 1. FIGO staging of vulvar carcinoma (1995)Â Stage

Clinical Findings

Carcinoma in situ

Confined to vulva or perineum, <2 cm in greatest dimension; no nodal metastasis

Stromal invasion <1.0 mm

Stromal invasion >1.0 mm

Confined to vulva or perineum, >2 cm; nodes are negative

III

Any size lesion with spread to urethra, vagina, or anus or with unilateral regional lymph node metastasis

IVA

Invasion of upper urethra, bladder mucosa, rectal mucosa, pelvic bone, or bilateral regional node metastasis

IVB

Any distant metastasis, includes pelvic lymph nodes

Figure 2. Labia majora lesion

of cancer. This may explain why the incidence of invasive vulvar cancer has remained stable even though the incidence of vulvar intraepithelial neoplasia has increased.[5,6,7] As already noted, there has been a substantial increase in the prevalence of VIN in young patients. VIN usually is multifocal and the most common sites are the hairless skin of interlabial folds, the posterior fourchette, and the perineum. Lesions may be macular or papular with a keratotic rough surface. White lesions are caused by hyperkeratosis, whereas red ones represent hypervascularity. Gray or brown lesions are produced by melanocytic overactivity and pigment incontinence.[7] Vulvoscopy and punch biopsies are the most important tools in the diagnostic approach. The use of a colposcope is of benefit in the evaluation of these lesions, but grading of the lesion is limited because of the keratin layer. Unlike the cervix and vagina, the histologic abnormality may extend beyond the area of a lesion visible with colposcopy. Wide local excision, removing a full thickness of skin encompassing epidermis and dermis with a 2-cm lateral margin, is sufficient treatment.[8] The histologic abnormality may extend beyond the clinically or colposcopical apparent lesion. Frozen-

Figure 3. Hemivulvectomy

section evaluation of the margins has been advocated by some authors to trim an additional margin and achieve complete excision. Nevertheless, a more conservative approach can be followed for microscopically positive margins waiting for the development of clinical lesions before proceeding with re-excision procedures.[9]

Staging Clinical criteria for staging of carcinoma of the vulva were formulated and adopted in 1970 by the FIGO. A modified surgical staging system was adopted in 1989 and revised in 1995 (Table 1).[10] The staging emphasizes definition of the primary tumor by size and location, including the involvement of structures contiguous with the vulva. Status of the nodes is based on surgical evaluation of the groin. The presence or absence of distant metastasis also is considered, including cystoscopic or proctoscopic evaluation. The survival results for stages I and II are similar and excellent, approximately 90% when no positive groin nodes are present.[11] Stage III lesions have a 50% 5-year survival rate, although successful treatment of 60â&#x20AC;&#x201C;70% of patients has been reported.[12] October 2015

Original article

Figure 4. Inguinal lymphadenectomy

Vulvar neoplasia - synopsis and treatment trends

Figure 5. Hemivulvectomy with bilateral inguinal

lymphadenectomy

Figure 6. Post hemivulvectomy status

Treatment Squamous carcinoma of the vulva usually proceeds in a predictable fashion through its regional lymphatics, first to the inguinal-femoral nodes and only then to pelvic and distant sites. Therefore, the superficial inguinal lymph nodes are the most common site for detecting metastasis. Metastasis to the contralateral nodes in the absence of involvement of the ipsilateral nodes is rare.[13] Midline lesions involving the clitoris may have spread to bilateral inguinal nodes. Direct metastasis of invasive squamous carcinoma of the vulva to the pelvic lymph nodes is rare, occurring with a frequency of 5% of all the cases, 15â&#x20AC;&#x201C;20% of the patients with positive groin nodes and nearly 0% of those with negative groin nodes.[14] Appropriate groin dissection is the most important factor in decreasing mortality for early vulvar cancer.[15] Patients who develop groin lymph nodal recurrence

have a 90% mortality.[16] When lymphadenectomy is performed, this should always include superficial and even deep lymph nodes and should be bilateral in presence of central location of the primary lesions or lymph node involvement. The modification of the groin dissection increases groin recurrence and mortality[17] . Size and location of the lesion are the primary parameters in deciding what procedure to perform. Early stage lesions are treated surgically. Advanced stage lesions are treated preferentially with chemoradiation. Pelvic exenteration with radical vulvectomy and inguinal lymph node dissection is a surgical option with significant physical and psychological morbidity as well as mortality. Microinvasive tumors (less than 1 mm of invasion, stage IA) may be treated by wide local excision with low risk of groin lymph node or vulvar recurrence.[18,19] A 1-cm lateral margin is recommended. Lesions less than 2 cm in diameter (stage IB) may be treated successfully by wide radical excision. A 2-cm lateral margin is obtained, and dissection is carried down to the fascia of the urogenital diaphragm for the deep margin. [20] When the invasion of the lesion is greater than 1 mm, ipsilateral groin lymph node dissection is recommended. This approach of radical local excision and ipsilateral node dissection works best for lesions that are lateral or posterior. Stage II lesions (greater than 2 cm in diameter) are treated by radical vulvectomy with inguinal-femoral lymph node dissection. Certain stage III lesions with extension to the lower urethra or proximal vagina may be treated the same way.[19,20,21]One of the most important recent developments in the treatment of vulvar carcinoma has been the individualization of treatment. Less radical surgery for early stage disease does not compromise survival. No lymphadenectomy is needed for patients with microinvasive tumors (stage IA). For unilateral lesions less than 2 cm in diameter, contralateral lymphadenectomy is not required unless lymph node metastasis is found in the ipsilateral side at the time of surgery.

Boiangiu A., Vladu C., Clim N., Filipescu A.

Performing separate incisions for inguinal lymph node dissection results in better wound healing with a reduced rate of infection [22,23]. In recent years, physicians have understood the fundamental importance of quality of life, and have tried to reduce permanent morbidity by tailoring surgery and attempting alternative treatments. Although the effective use of radiation therapy for the treatment of vulvar carcinoma has been demonstrated in prospective and retrospective studies, the use of elective groin irradiation in patients with vulvar cancer is controversial. Locoregional control, survival rates, and complications may be improved by the use of radiation in advanced vulvar cancer. In particular, the need for exenterative surgery can be reduced with the utilization of preoperative radiation[24]. Therefore in patients affected by vulvar cancer with multiple lymph node metastases, radical surgery followed by adjuvant chemotherapy is a feasible strategy, with an acceptable short- and longterm complication rate. Results in terms of overall survival and disease-free survival are promising. Further studies are needed to determine the optimal combined modality treatment. The role of chemotherapy alone will probably remain confined to

palliative treatment of metastatic and recurrent tumors.[25,26]

Conclusions One of the most important recent developments in the treatment of vulvar carcinoma has been the individualization of treatment. Surgery remains the gold standard in patients with primary vulvar cancer. The “triple incision”, a more conservative technique that consists of separation of the treatment of the primary lesion from the dissection of the regional lymph nodes assure less wound complications and better wound healing. Less radical surgery for early stage disease does not compromise survival. In the future the trend will be to adopt more frequently such a procedure in a neoadjuvant setting in order to reduce surgical aggressiveness and therefore reduce postoperative morbidity and increase the quality of life of these patients. This work is licensed under a Creative Commons Attribution 4 .0 Unported License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc/4.0/

References [1] H. P. van de Nieuwenhof, I. A. M. van der Avoort, and J. A. de Hullu, “Review of squamous premalignant vulvar lesions,”Critical Reviews in Oncology/Hematology, vol. 68, no. 2, pp.131–156, 2008. [2] M. R. Nucci and E. Oliva, in Gynecologic Pathology: A Volume in Foundation in Diagnostic Pathology Series, Churchill Livingstone, New York, NY, USA, 2009 [3] Ansink A. Vulvar squamous cell carcinoma. Semin Dermatol 1996; 15:51. [4] Madsen BS, Jensen HL, van den Brule AJ, et al. Risk factors for invasive squamous cell carcinoma of the vulva and vagina--population-based casecontrol study in Denmark. Int J Cancer 2008; 122:2827. [5] de Koning MN, Quint WG, Pirog EC. Prevalence of mucosal and cutaneous human papillomaviruses in different histologic subtypes of vulvar carcinoma. Mod Pathol 2008; 21:334. [6] Monk BJ, Burger RA, Lin F, et al. Prognostic significance of human papillomavirus DNA in vulvar carcinoma. Obstet Gynecol 1995; 85:709. [7] Insinga RP, Liaw KL, Johnson LG, Madeleine MM. A systematic review of the prevalence and attribution of human papillomavirus types among cervical, vaginal, and vulvar precancers and cancers in the United States. Cancer Epidemiol Biomarkers Prev 2008; 17:1611. [8]Joura EA: Epidemiology, diagnosis and treatment of vulvar intraepithelial neoplasia. Curr Opin Obstet Gynecol 14(1): 39–43, 2002 [9] Hillemanns P, Wang X, Staehle S, Michels W, Dannecker C: Evaluation of different treatment modalities for vulvar intraepithelial neoplasia (VIN): CO(2) laser vaporization, photodynamic therapy, excision and vulvectomy. Gynecol Oncol 100(2): 271–5, 2006 [10] Creasman WT: New gynecologic cancer staging. Gynecol Oncol 58: 157, 1995 [11] Microinvasive cancer of the vulva: Report of the ISSVD task force. J Reprod Med 29: 454, 1984 [12]Kosary CL: FIGO stage, histology, histologic grade, age and race as prognostic factors in determining survival for cancers of the female gynecological system: An analysis of 1973-87 SEER cases of cancers of the endometrium, cervix, ovary, vulva and vagina. Semin Surg Oncol 10: 31, 1994 [13] Hoffman JS, Kumar NB, Morley GW: Prognostic significance of groin lymph node metastasis in squamous cell carcinoma of the vulva. Obstet

Gynecol 66: 402, 1985 [14] Cavanagh D: Vulvar Cancer-continuing evolution in management. Gynecol Oncol 66: 362–7, 1997 [15] Raspagliesi F, Hanozet F, Ditto A et al: Clinical and pathological prognostic factors in squamous cell carcinoma of the vulva. Gynecol Oncol 102(2): 333–7, 2006 [16] Marsden DE, Hacker NF: Contemporary management of primary carcinoma of the vulva. Surg Clin North Am 81(4): 799–813, 2001 [17] Stehman FB, Bundy BN et al: Early stage I carcinoma of the vulva treated with ipsilateral superficial inguinal lymphadenectomy and modified radical hemivulvectomy: a prospective study of the GOG. Obstet Gynecol 79(4): 490–497, 1992 [18] Kelley JL III, Burke TW, Tornos C et al: Minimally invasive vulvar carcinoma: An indication for conservative surgical therapy. Gynecol Oncol 144: 240, 1991 [19] Magrina JF, Gonzalez-Bosquet J, Weaver AL et al: Squamous cell carcinoma of the vulva stage IA: Long-term results. Gynecol Oncol 76: 24, 2000 [20] Taussig F: Carcinoma to the vulva: an analysis of 155 cases. Am J Obstet Gynecol 40: 764, 1940 [21] Way S: Carcinoma to the vulva: an analysis of 155 cases. Am J Obstet Gynecol 791: 692, 1960 [22] Heaps JM, Fu YS, Montz FJ et al: Surgical-pathologic variables predictive of local recurrence in squamous cell carcinoma of the vulva. Gynecol Oncol 38: 309, 1990 [23] De Hullu JA, Hollema H, Lolkema S et al: Vulvar carcinoma. The price of less radical surgery. Cancer 95(11): 2331–8, 2002 [24] Homesley HD, Bundy BN, Sedlis A et al: Radiation therapy versus pelvic node resection for carcinoma of the vulva with positive groin nodes. Obstet Gynecol 68: 733, 1986 [25] Han SC, Kim DH, Higgins SA et al: Chemoradiation as primary or adjuvant treatment for locally advanced carcinoma of the vulva. Int J Radiat Oncol Biol Phys 47: 1235, 2000 [26] Van Doorn HC, Ansink A, Verhaar-Langereis M, Stalpers L. Neoadjuvant chemoradiation for advanced primary vulvar cancer. Cochrane Database Syst Rev 3: CD003752, 2006

October 2015

Original article

Hpv – silent and fearsome enemy in cervical cancer oncogenesis

HPV – SILENT AND FEARSOME ENEMY IN CERVICAL CANCER ONCOGENESIS Roxana Penciu, Mihai Zisu, Vlad Tica

Abstract Keywords: HPV, oncogenesis, cervical cancer

Received: October 2015 Reviewed: October 2015 Accepted: October 2015

Cite this article: Penciu R., Zisu M., Tica V. Hpv – silent and fearsome enemy in cervical cancer oncogenesis Rom J Oncol Hematol. 2015; 7(2):94-97

Cervical cancer is the fourth most frequent feminine cancer in the world; 527,624 new cases and 265,653 deaths were estimated in 2012. Globally, cervical cancer’s mortality rates are substantially lower than the incidence, with a ratio mortality / incidence of 50%. The most frequent types of cervical cancer are the squamous ones and, subsequently, adenocarcinomas. Causal connection HPV (human papilloma virus) – cervical cancer is supported by the fact that persistent infection with oncogenic HPV serotypes is considered to be the necessary cause for cervical cancer; presence of oncogenic HPV subtypes is revealed in 99,7% of cervical cancer biopsies. HPV is capable of being transferred by direct contact, by free viral particles entering through small skin or mucous gaps. The target of HPV infection is the keratinocyte, which will contain 50-100 HPV virions. HPV has a sophisticated mechanism to hide and the immune human system cannot always eliminate or control the HPV infection. One of the most effective hiding mechanisms is represented by the viral infection of only the basal cells, without invading the circulatory system, so without generating viremia. Oncogenic process takes generally up to 10-40 years (even if, rarely, it can be reduced to 1-2 years). One of the two HPV genome regions is Open Reading Frames – which contains an Early Region (E), necessary for the replication, cellular transformation and for the viral transcription control. Within E, E2 gene has an important role in DNA replication as it normally (among other functions) inhibits the expression of E6 and E7 oncogenes. Persistent infection is associated with the inclusion of the viral DNA into the basal cells’ genoma. E6 and E7 are not blocked anymore by E2. E6 oncoprotein inhibits the TP53 gene while E7 oncoprotein inhibits the Rb blocking. Those changes disturb the cellular cycle and produce uncontrolled cellular multiplication and genomic instability. Finally, they can produce irreversible cellular changes. The importance of discovering this mechanism and its medical utility was emphasized by granting the Nobel Prize in 2008 to Professor Harald zur Hausen – for discovering the causal role of papilloma viruses in cervical cancer - which contributed to creating a successfully anti-HPV vaccine.

Roxana Penciu, Mihai Zisu, Vlad Tica

Rezumat Cuvinte-cheie: HPV, oncogeneză, cancer de col uterin

Cancerul de col uterin este pe locul 4 în lume ca incidenţă între neoplaziile feminine. Este, astfel, estimat un număr de 527.624 cazuri nou diagnosticate și 265.653 decese în 2012. În total, rata mortalității cancerului de col uterin este substanțial mai mică decât incidența, cu un raport mortalitate/incidență de 50%. Predomină cazurile de cancer de col uterin de tip scuamos, urmate de adenocarcinoame. Legătura cauzală HPV (human papilloma virus) – CCU (cancer de col uterin) este susținută prin faptul că infecția persistentă cu serotipuri oncogenice de HPV este considerată cauza necesară pentru apariția cancerului de col uterin; prezența serotipurilor HPV oncogenice este relevată în 99,7% din biopsiile de CCU. Transmiterea HPV se face prin contact direct, prin particule virale libere care pătrund prin mici breșe ale pielii sau mucoasei. Ținta infectării de către HPV este cheratinocitul, care va conține aproximativ 50–100 virioni HPV. HPV prezintă un mecanism sofisticat de camuflaj, iar sistemul imun uman nu reușește întotdeauna să elimine sau să controleze infecția HPV. Unul dintre cele mai eficace mecanisme de camuflaj este reprezentat de infecţia virală doar a celulelor stratului epitelial cervical bazal, fără invazia sistemului sangvin, deci fără a produce viremie. Persistența infecției se asociază cu riscul ca genomul viral să se integreze în genomul celulelor bazale. Procesul oncogenic durează în general 10-40 ani (deși, în cazuri rare, el poate fi redus și la 1-2 ani). Una dintre cele două regiuni ale genomului HPV este Open Reading Frames – care conţine o „Early Region” (E) necesară pentru replicare, transformare celulară şi pentru controlul transcripţiei virale. În cadrul E, gena E2 are un rol important în replicarea ADN deoarece ea (printre alte funcţii) inhibă exresia oncogenelor E6 şi E7. Persistenţa infecţiei este asociată cu pătrunderea ADN-ului viral în genomul celulelor stratului bazal. E6 şi E7 nu mai sunt blocate de E2. Oncoprotena E6 inhibă gena TP53 iar E7 inhibă blocarea Rb. Aceste modificări afectează ciclul celular şi produc multiplicare celulară necontrolată şi instabilitate genomică. În final, pot produce modificări celulare ireversibile. Importanța descoperirii acestui mecanism și a relevanței sale medicale a fost subliniată prin acordarea Premiului Nobel în 2008 Profesorului Harald zur Hausen - “pentru descoperirea rolului cauzal al virusurilor papilomatoase în cancerul cervical care a dus la dezvoltarea unui vaccin anti-HPV plin de succes”.

Cervical cancer is the fourth most frequent feminine cancer in the world. Available data suggest a number of 527,624 new cases and 265,653 deaths in 2012. Globally, cervical cancer’s mortality rates are substantially lower than the incidence, with a ratio mortality-incidence of 50% (GLOBOCAN 2012). The most frequent types of cervical cancer are the squamous ones and, secondly, adenocarcinomas. (1-5) In Romania, women population includes about 9.54 million individuals aged 15 years or more, which have risk of cervical cancer. Actual estimations indicate that, in Romania, every year, 4343 women are diagnosed with cervical cancer and 1909 die because of it. Cervical cancer, in Romania, is the third most frequent cancer in women and the second most frequent cancer type in women with ages between 15 and 44 years. (1) Causal relation HPV (human papilloma virus) – CC (cervical cancer) is supported by the fact that persistent infection with oncogenic HPV

serotypes is considered to be the necessary cause for cervical cancer. The presence of oncogenic HPV is revealed in 99,7% of cervical cancer biopsies. (6, 7) therefore, HPV is accepted as the principal causal factor for cervical cancer. Presently, 150 HPV subtypes are discovered; 40 of them can be sexually transmitted. There are two subtypes of HPV strains. They are classified as low risk strains and high risk strains (14 subtypes: 16, 18, 31, 33, 39, 45, 51, 52, 56, 58, 59, 66, 68 and 73) – the last ones representing the cause of more than 99% of cervical cancers. Among the high risk strains, subtypes 16 and 18 are responsible of about 70% of cervical cancer cases. (1) One should emphasize, as a severity factor, that 50-80% of women will probably be HPV infected during their whole life. Up to 50% of them will be infected with an oncogenic HPV serotype – and these infections are usually asymptomatic. (8-10) In Romania recent statistical data (2012) show that every year 1909 women October 2015

Original article

Figure 1. Invasive cervical cancer ( Personal archives)

die because of cervical cancer. Cervical cancer is placed among the mortality causes and it represents the most important cause of death in women with ages between 15 and 44 years. (11)

Oncogenesis Papillomaviruses are small nonenveloped viruses with 55-nm-diameter icosahedral capsids which contain double-stranded DNA genomes of about 8,000 bp. These viruses are widely distributed throughout the animal kingdom and they specifically infect squamous epithelia and cause the generation of warts. The infectious etiology of warts was suspected and eventually proven in the 19th century. One of the first recorded experimental wart transmission cases in humans seems to have been accidental and was reported in 1845 by a certain Chandler, who “when removing a large acicular condyloma with his instrument injured his assistance beneath the thumbnail. On the injured place appeared after a short time a wart, which was repeatedly destroyed, but reappeared, until the nail of the injured thumb was removed”.(12) Ullmann also noted a similar accidental transmission of laryngeal papillomas and he did self-inoculation experiments with laryngeal papilloma extracts. He applied them to scarified sites on his forearm, and warts yielded after a lengthy latency period of about 9 months. (12) Genital warts and cervical cancer were considered to be manifestations of then-common venereal diseases like syphilis and gonorrhea. This theory was contested in a paper published in 1917. Extracts from a penile condyloma that was harvested from a young medical student who did not exhibit other overt symptoms of venereal diseases were inoculated in sites on the forearms of the author and his assistant as well as the genital mucosa of a “virgo intacta” woman. After a period of 2 months and a half, the unfortunate female subject developed genital condyloma, and the two male subjects had flat warts on the forearms. (12) HPV is capable to be transferred by direct contact, by free viral particles entering through small skin or mucous gaps. The target of HPV infection is the keratinocyte - which will contain about 50-100 HPV virions. (13, 14) Infectious HPV cycle is represented

Hpv – silent and fearsome enemy in cervical cancer oncogenesis

Figure 2. Cervical adenocarcinoma ( Personal archives)

by: basal cells infection, inclusion of viral DNA in the keratinocyte genoma, replication of viral DNA and the releasing virions with desquamated cells. (13, 14) It seems that HPV can be eliminated in 8 to 12 months (rarely up to 2 years) out of the body. A possible theory is that the host’s immune system finds and eliminates basal infected cells with HPV. In 10% of cases, HPV is not eliminated and persists after 2 years from the initial infection. (15, 16) Low-risk mucosal HPVs such as HPV-6 and HPV-11 cause genital warts (condyloma accuminata), whereas the high-risk HPVs cause squamous intraepithelial lesions that can progress to an invasive squamous cell carcinoma. (12) Infection with HPV typically leads to benign epithelial proliferations. A growing number of viral subsets have been associated with epithelial cancers. However, most of those cases do not progress to cancer, even in patients that were infected with these oncogenic, “high-risk” subsets. Malignant transformation, if it occurs, tends to appear only after a long latency period. This suggests that infection with HPV is necessary, but not sufficient for developing of HPV-associated cancers. (15) Viral particles consist of about 7900 basepairs (7.9 kbp) long circular DNA molecules which are wrapped into a protein shell. The HPV genome can be divided into two regions: Upstream Regulatory Region (URR) and Open Reading Frames (ORFs). URR does not code for proteins, but it contains cis-elements which are required for the regulation of gene’s expression and replication of the genome, and its packaging into virus particles. ORFs can be divided into the Early Region (E), which is necessary for the replication, cellular transformation and for control of viral transcription, and Late Region (L) that is capable to code the capsid proteins that comprises the outer coat of the virus. Within the Early Regions (E) it can be possible to distinguish different genes with specific functions as E1 and E2. These two genes have an important role in basal DNA replication. During viral persistence, the immune system is capable to keep the infection in this state. E2 normally participates in the regulation of LCR (low-copy repeats) transcriptions, and decreases the expression of E6 and E7. (16)

Roxana Penciu, Mihai Zisu, Vlad Tica

Infection’s persistence is associated with the risk that the viral genoma can enter in basal cells’ genoma. They are still generating viral material, the same time with viral oncogenes expression E6 and E7 (because they are not blocked by E2). Blocking the TP53 gene (by E6 oncoprotein) and the inhibition of the Rb blocking (by E7 oncoprotein) disturb the cellular cycle and produce uncontrolled multiplication up to the apoptosis arrest. Persistent HPV infection generates an uncontrolled cellular multiplication and genomic instability. Finally, they produce irreversible cellular changes. (2, 17, 18) Oncogenic process takes generally up to 10-40 years (even if, rarely, it can be reduced to 1-2 years. (17, 18) HPV has a sophisticated mechanism to hide – so that the immune human system cannot always eliminate or control the HPV infection. The virus infects the cells of basal layer without invading the circulatory system, therefore without generating viremia. By lowering the secretion of interferon in tissues, the virus causes local immunosuppression. More, the virus is released from the desquamated cells, on pavimental epithelia surface – in the vagina – so, far away from the antigen presenting epithelial cells and macrophages – which are present in the blood and subepithelial tissue. Finally, HPV infection does not determine destruction of host’s cells; therefore it does not produce proinflammatory cytokines with subsequent inflammatory reaction. (2, 17, 18) The importance of discovering this mechanism and its medical utility was emphasized by granting the Nobel Prize in 2008 to Professor Harald zur Hausen – for the discovery of the causal role of papilloma viruses in cervical cancer, discovery that contributed to creating a successfully antiHPV vaccine. (17, 18) The screening for cervical cancer implies Babes-Papanicolaou testing. Different guidelines recommend different age of beginning / stopping and different frequency of this screening. It is important to respect the collecting conditions – no sexual contact or vaginal washing 24 - 48 hours before the test. Before collection, the physician needs to treat any vaginal or

cervical pathology, because they can influence the results of the test. In case of any dysplastic lesion, DNA genotyping is necessary, in order to identify the HPV presence. (19) Associated factors for HPV persistence and progression to cervical cancer could be immunosuppression, multiparity, first pregnancy at an early age, oral contraceptives for long periods, smoking, sexually transmitted diseases (e.g.: chlamydia trachomatis or herpes simplex virus 2) and HIV infection. (19) On 10th of December 2014, FDA (Food and Drug Association) announced the approval of a 9-valent HPV vaccine. This vaccine includes 5 new HPV types – 31, 33, 45, 52, 58 besides the previously included HPV types 6, 11, 16 and 18. It is estimated that the protection against the new 5 types will reduce in the future the HPV generated cervical cancer with 14% in women and with 5% in men, upgrading vaccination and leading to cervical cancer lowering rate with 70-90%. (20-24) On 27 February 2015, ACIP centers (Advisory Committee on Immunization Practices) recommended that anti-HPV – 9-valent vaccine to be added as an option of vaccination calendar for teens and young adults. ACIP recommends that the new or previously introduced vaccines can be alternatively used as routine vaccinations. Anti-HPV vaccine is recommended for both previously unvaccinated girls and women with ages between 13 and 16 years as well as for unvaccinated boys and men between 13 and 21 years. (20-24) According to ACIP the administration of the 3 doses (therefore the medical visits) can be more flexibles, so that the second dose can be given one or two months after the first one and the third one, 6 months after the first dose. (20-24)

References 1. Human Papillomavirus and Related Diseases, Summary Report 2014. 2. Stanley M. - Vaccine 2006, Vol. 24, Suppl 3. 3. Stanley M - Vaccine 2008, Vol. 26, Suppl 10. 4. Stanley M - Vaccine 2012, Vol. 30, Suppl 5. 5. IARC Monographs 2007, Vol. 90. 6. Bosch FX et al. J Nat Cancer Inst Monograph 2003; 31: 3–13. 7. Walboomers JM et al. J Pathol 1999; 189: 12-19. 8. Baseman JG et al. J Clin Virol 2005; 32 Suppl 1; S16-24. 9. Ho GY et al. N Engl J Med 1998; 338: 423–8. 10. Brown DR et al. J Infect Dis 2005; 191: 182–92. 11. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http:// globocan.iarc.fr, accessed on 15/01/2014. 12. Mechanisms of Human Papillomavirus-Induced Oncogenesis - Karl HYPERLINK “http://www.ncbi.nlm.nih.gov/pubmed/?term=M%26%23 x000fc%3Bnger%20K%5Bauth%5D”Münger,* Amy Baldwin, Kirsten M. Edwards, Hiroyuki Hayakawa, Christine L. Nguyen, Michael Owens, Miranda Grace, and KyungWon Huh; J Virol. 2004 Nov; 78(21): 11451–11460. 13. Bryan JT, Brown DR. Virology. 2001;281:35–42. 14. Meyers C, Bromberg-White JL, Zhang J, et al. J Virol. 2002;76:4723– 4733. 15. The Oncogenic Potential of Human Papillomaviruses: A Review on the Role of Host Genetics and Environmental Cofactors -V.K. Madkan; R.H.

Cook-Norris; M.C. Steadman; A. Arora; N. Mendoza; S.K. Tyring; The British Journal of Dermatology. 2007;157(2):228-241. 16. Oncogenic Aspects of HPV Infections of the Female Genital Tract - Josko Zekan, Maja Sirotkovic-Skerlev and Mihael Skerlev;DOI: 10.5772/1916; Biochemistry, Genetics and Molecular Biology ISBN 978-953-307-593-8 17. Culp TD, Christensen ND. Virology. 2004;319:152–161. 18. Carter JJ, et al. J Infect Dis. 2000; 181:1911–1919. 19. Cervical cancer, human papillomavirus (HPV), and HPV vaccines -WHO Document Production Services, Geneva, Switzerland, WHO/RHR/08.14. 20. 9-valent Human Papillomavirus Virus (HPV) Vaccine -Marcia L. Buck, Pharm.D., FCCP, FPPAG- Pediatr Pharm. 2015;21(3) 21. U.S. Food and Drug Administration. FDA approves Gardasil 9 for prevention of certain cancers caused by five additional types of HPV. December 10, 2014. Available at: http://www.medicine.virginia.edu/ clinical/departments/pediatrics/education/pharm-news (accessed 2/23/15). 22. Gardasil® 9 prescribing information. Merck & Co., Inc. February 2015. Available at: http://www.merck.com/product/usa/pi_circulars/g/ gardasil_9/gardasil_9_pi.pdf (accessed 3/7/15). 23. Serrano B, Alemany L, Tous S, et al. Potential impact of a nine-valent vaccine in human papillomavirus related cervical disease. Infect Agents Cancer 2012;7:38. Available at: http://www.infectagentscancer.com/ content/7/1/38 (accessed 3/7/15). 24. Centers for Disease Control and Prevention. Human papillomavirus vaccination: recommendation of the Advisory Committee on Immunization Practices (ACIP). Morbid Mortal Weekly Report 2014;63(5):1–29.

October 2015

Review

The role of urinary tract resections in advanced-stage ovarian cancer. A Literature Review

THE ROLE OF URINARY TRACT RESECTIONS IN ADVANCED-STAGE OVARIAN CANCER – A LITERATURE REVIEW Nicolae Bacalbasa (1) ,Olivia Ionescu (2), “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania 2“ BUCUR” MATERNITY HOSPITAL BUCHAREST Corresponding author: Nicolae Bacalbașa, Adress: Dimitrie Racoviță Street, no. 2, Bucharest, Romania E-mail: nicolae_bacalbasa@yahoo.ro Phone no: +40723540426

Open Access Article

Abstract Keywords: ovarian cancer, ureteral resections, urinary tract, ureteroneocystostomy;

Abbreviations: ASOC=advancedstage ovarian cancer; CS= cytoreductive surgery; RD=residual disease;PCS=primary cytoreductive surgery; UTR=urinary tract reconstruction; SCS=secondary cytoreductive surgery; IHP=inferior hypogastric plexus; Received: October 2015 Reviewed: October 2015 Accepted: October 2015

Rationale: Advanced –stage ovarian cancer(ASOC) can invade or obstruct the lower urinary tract. Radical surgery, the mainstay treatment, may require extension of the surgical procedures to the urinary structures. Objective: The aim of this review is to present the incidence and types of urinary tract resections, the methods used for urinary tract reconstruction (UTR), as well as the assessment of preoperative factors influencing the occurrence of urological procedures and their impact on bladder function. Material and method: Information about the urological procedures with attention to the clinical history, surgical technique and patient outcomes was searched through Pubmed and Medline using controlled vocabulary (e.g urological procedures) and key words (ureteric replacement). Systematic reviews and retrospective studies were analyzed. No restrictions regarding date or language were used. Conclusions: Optimal cytoreductive surgery for ovarian cancer often requires excision of a portion of the bladder or ureter. The Bricker ileal conduit remains the gold standard for the treatment of severe urinary tract injuries or for pelvic exenterative procedures. Alternatively, after resection of a portion of the pelvic ureter, the urinary tract can be successfully reconstructed with direct ureteroneocystostomy.

Introduction

The effectiveness of optimal cytoreductive surgery (CS) for the management of advanced-stage ovarian cancer(ASOC) is generally accepted and its completeness is necessary to maximize survival [1,2]. The notion of optimal debulking surgery has changed over time from residual disease(RD) 2 cm to 1 cm and currently to no gross RD. Maximal cytoreduction to a visibly disease-free state has been demonstrated to be the most powerful determinant of Cite this article: median and 5-year survival rates [3]. Bacalbasa N., Ionescu O. ASOC frequently extends beyond the anatomic The role of urinary tract resections in advanced- boundary of origin due to direct extension or sestage ovarian cancer. rosal implantation [4]. The intimately anatomical – A Literature Review association of the female genital tract with renal Rom J Oncol Hematol. excretory pathways may imply accidental opera2015; 7(2):100-103

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tive injuries to the urological structures during , even relatively straightforward, gynecologic operations [5]. Moreover, the complete eradication of the tumor requires sometimes the partial or total excision of a portion of the bladder or ureter and, therefore, necessitates urological procedures both intent, demolitive and reconstructive [6]. Taking into account these considerations, the aim of this article is to make a review of the most important types of urologic procedures and to clarify their relevance during the surgical treatment of ASOC.

Ureteral resections and methods of repair The incidence of ureteral resection for PCS reported in the literature is 0.7% [7]. For patients undergoing rectosigmoid colectomy for resection of

Bacalbasa N., Ionescu O.

primary or recurrent gynecologic cancer, the incidence of concomitant ureteral resection is higher (6%) [8]. The reported types of injury are: transections, avulsion or severe crush injury of the distal ureter[9,10] and a possible risk factor predicting the probability of iatrogenic ureteral lesions include: extensive previous pelvic surgery, extensive pelvic disease, obesity, severe haemorrhage [11]. Ureteroneocystostomy followed by a tunneled, antireflux anastomosis is recommended by most authors, as well as the election method of repair when an isolated injury within the distal 5 cm of the pelvic ureter occurs during an operation[ 9,11,12,13] . It appears to be agreed due to the high success rate, ease, and security of the procedure. When an isolated injury is recognized at the proximal pelvic ureter (eg, pelvic brim), the optimal management is debatable [8,14]. An extensively mobilized distal ureter results in an important devascularization of the ureter that is distal to the lesion and therefore in a suboptimal anastomotic healing. In this cases, the solution is also ureteroneocystostomy [15]. On the other hand, bridging a large ureteral defect with ureteroneocystostomy may not be secure especially in patients with a contracted or radiated bladder [16]. Stenting the ureteral anastomosis and placing of a closed-suction drain in the vicinity of the ureteral anastomosis are generally considered to bring multiple benefits. As the ureter is stabilized and immobile during healing and has no tendency to be angulated, the likelihood of urinary extravasation is reduced and the repair is isolated from potential infected fluid collections, retroperitoneal fibrosis, and cancer[8,9,17].

Urinary tract reconstruction The treatment of advanced or recurrent ovarian cancer often entails exenterative type procedures requiring reconstruction of the pelvic viscera [18]. When the pelvic ureter is completely resected the solutions are: ureteroneocystostomy (using a psoas hitch, bladder mobilization, bladder flap, bladder elongation, mobilization of the kidney), ileal ureter, transureteroureterostomy, cutaneous ureterostomy, autotransplantation, or nephrectomy [19,20]. While some sequelae may be treated with drainage or primary repair, the Bricker ileal conduit remains the gold standard for the treatment of severe urinary tract injuries or for pelvic exenterative procedures[21]. Goodwin described firstly the use of ileum for ureteric replacement in 1959 and helped coin the phrase â&#x20AC;&#x153;ileal ureterâ&#x20AC;?[22]. Other reports in the urologic literature have demonstrated that use of ileum for ureteric replacement either isolated or in conjunction with the cecum is a standard in urinary tract reconstruction (UTR) [18,19]. The essential benefit of both procedures, an ileocystoplasty and an ileal interposition is the preservation of urethral voiding. An ileal conduit is advantageous because it creates a low-pressure reservoir with little risk for obstruction, but the possible reported compli-

cations are: stomal hernias, stomal stenosis, uretero-ileal strictures, reflux, hydronephrosis, stone formation, electrolyte disturbances, a cutaneous stoma and thus loss of normal micturition [20]. The bowel segments used for urinary tract reconstruction may be either small or large bowel. While the jejunum has a high absorption rate and can lead to electrolyte disorders, the colon should be avoided when its segments are affected by diverticular disease or are significantly radiated such as recto-sigmoid colon which can result in fistula formation[21,22]. Currently, non- irradiated ileum is the most frequently used for urinary tract reconstruction (UTR) because it has a rich vascularization and can assure a very low-pressure system when detubularized [23]. However, after using an ileal segment for UTR, the posibble complications are: hyperchloremic metabolic acidosis, which may cause skeletal demineralization and osteoporosis [24], and a malign transformation of the remaining intestinal and bladder epithelium [25]. Elkas et al [21] reported a series series of ten patients with recurrent ovarian or cervical carcinoma who underwent lower UTR with ileum as part of tumor extirpation or repair of radiation sequalae. Patients who underwent extensive ureteral resection or bypass, ureteroneocystotomy with or without a Psoas hitch, a Boari was performed. When the length of residual ureteral was insufficient an ileal interposition was the best option, in oppositon to a transureteroureterostomy, which potentially compromises a normally functioning contralateral side. All patients without significant renal insufficiency or small bowel pathology are candidates for an ileal interposition. In the same study, two women with low-grade ovarian neoplasms and isolated pelvic recurrences, underwent a subtotal cystectomy at time of a secondary cytoreductive surgery (SCS) procedure. Each woman required a partial cystectomy, ileocystoplasty, and unilateral distal ureteral resection as part of SCS. Before considering a subtotal cystectomy and ileocystoplasty, authors recommend that vesical margins should be grossly and histologically negative [26]. The optimal candidates for a subtotal cystectomy and ileocystoplasty are those with small (<2 cm) central or posterior recurrences in which adequate margins can be obtained while preserving the patientâ&#x20AC;&#x2122;s bladder neck to include at least the urethral portion of the trigone [26]. The bladder continence can be retained even after radical cystectomy due to the presence of the rhabdosphincter muscle located in the mid to lower third of the urethra [20,26]. A healthy appearing ileum segment with a rich blood supply can be used to repair urinary tract sequelae from pelvic radiation such as ureteral obstruction or stricture, vesicovaginal and ureterovaginal fistulas, bladder fibrosis and contracture. Because irradiated tissues have a prolonged healing, treatment of the mentioned sequelae should be conservative for up to 2 months. Moreover, October 2015

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The role of urinary tract resections in advanced-stage ovarian cancer. A Literature Review

Table 1. Major post-operative complications34] Early non-urological -Hemorrhage -Sepsis -Abdominal abscess -Wound infection/dehiscence -Heart dysfunction -Acute abdominal pain -Deep Venous Thrombosis -Acute renal failure -Bowel occlusion -Vaginal vault dehiscence Early and late urological -Urinary dysfunction (early)a -Fistula -Vesico-Vaginal -Ureteral-Abdominal -Ureteral stenosis 2 (0.3) e 2 (0.3) a

Voiding dysfunction, mild incontinence

the area of reconstructions can be covered with omental J-flaps which increases the vascularization the tissues and decreases the fistula rate. In the same way, the application of fibrin tissue adhesives may prevent urinary drainage at anastomosis sites [26].

Retrospectively analyzing a larger single-institution series of patients submitted to major gynecological surgery, the report of Constantini et al [27] tried identify possible preoperative predictive variables related to the occurrence of urological procedures. Firstly, they found that, for ASOC, hydronephrosis is the major pre-operative risk factor predicting the involvement of the urinary tract. In order to preserve the renal function, a preferable positioning of nephrostomy or â&#x20AC;&#x153;double jâ&#x20AC;? stent before surgery should be indicated [28]. Secondly, recurrent ovarian cancer after previous treatmentPCS, adjuvant chemotherapy- is another predictive factor as the pelvic anatomy and tissue texture are consequently modified, therefore demanding urological demolitive and reconstructive procedures [29].Overall, in the literature data, the rate of urological complications after gynecological procedures is 3% [30,31] and 8,8% for non-urological complicatios (sepsis, hemorrhage) [32]; In the early postoperative period, the rate of vesicovaginal or uretero-vaginal fistulas ranges from 0.9 to 2%, after radical hysterectomy [33]. The major post-operative complications according to Dindo et el [34] are presented in Table 1.

exenteration without consideration for the autonomic nerves can lead to postoperative bladder dysfunction in patients treated for gynecological [36, 37] . The incidence of postoperative bladder dysfunction after conventional radical hysterectomy has been reported to occur in 70â&#x20AC;&#x201C;85% of patients. Lesions of the autonomic nerves of the inferior hypogastric plexus (IHP) may result in increased resistance at the bladder neck and motor and sensory impairment of the detrusor [38]. In the retrospective study of Kato et al [39], a greater bladder dysfunction was observed in patients in whom unilateral nerve-sparing radical hysterectomy was performed than in those with bilateral nerve-sparing radical hysterectomy. In the same study, 73% women with bilateral or unilateral nerve-sparing surgery presented preoperative storage symptoms such as increased frequency of micturition. This may be due to a smaller bladder capacity caused by compression from the pelvic tumor. After cytoreductive surgery, this symptom tended to be resolved postoperatively. Moreover, 3 months after surgery, women were inable to maintain adequate detrusor contraction or relax the urethra, which lead to a weak urinary stream. Long-term severe intrinsic bladder dysfunction consisting of urgency, urge incontinence, stress incontinence, contracted bladder, or periurethral fibrosis can also occur [40]. Therefore, preoperative assessments of urinary symptoms in women undergoing radical pelvic procedures are very important in order to evaluate the postoperative bladder dysfunction.

Postoperative bladder function

Conclusions

The sympathetic and parasympathetic nervous systems in the pelvis are essential for successful micturition [35]. Performing modified posterior

Debulking surgery for advanced ovarian cancer can necessitate partial resection of the urinary tract to achieve optimal cytoreduction.

Predictors of and complications after urological procedures

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Bacalbasa N., Ionescu O.

The close proximity of the urinary tract to the reproductive organs makes it highly susceptible to be involved in radical surgery or injured from adjuvant therapy. Pre-operative hydronephrosis and the recurrent ovarian cancer are warning factors associated to a higher probability of urologic procedures. When significant injury to the pelvic ureter occurs during radical pelvic surgery, UTR can be successfully realized with direct ureteroneocystostomy. As an alternative, a more limited bladder or ureteral resection with reconstruction using ileum for interposition or augmentation may offer preservation of urethral

voiding. A nerve-sparing modified posterior exenteration is feasible, effective and avoids postoperative bladder dysfunction. However, as the surgical techniques evolve, anterior reconstruction or even an orthotopic bladder substitution may be the gold standard treatment for lower UTR. This work is licensed under a Creative Commons Attribution 4 .0 Unported License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc/4.0/

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Arch Esp Urol 2003;56:69–71. 21. Bricker EM. Bladder substitution after pelvic evisceration. Surg Clin North Am 1950;30:1511 22. Goodwin WE, Winter CC, Turner RD. Replacement of the urter by small intestine—clinical application and results of the ileal ureter. J Urol 1959;81:406–18. 23. Elkas JC, Berek JS, Leuchter R ,Lagasse LD, Karlan BY. Lower urinary tract reconstruction with ileum in the treatment of gynecologic malignancies. Gynecologic Oncology 97 ;2005;685–692. 24. Nurse DE, Mundy AR. Metabolic complications and cystoplasty. Br J Urol 1989;63:165– 70. 25. Nurse DE, Mundy AR. Assessment of the malignant potential of cystoplasty. Br J Urol 1989;64:489– 92. 26. Evans LA, Ferguson KH, Rozanski TA, Morey AF. Fibrin sealant for the management of genitourinary injuries, fistulas and surgical complications. J Urol 2003;169:1360 – 2. 27. Costantini B, Vizzielli G, Fanfani F, D’Addessi A, Ercoli A, Avenia N, Margariti PA, Gallotta V, Scambia G, Fagotti A. Urologic surgery in gynecologic oncology: A large single-institution experience. EJSO 40;2014;756-761. 28. Stefanovic A, Jeremic K, Kadija S, et al. Intestinal surgery in treatment of advanced ovarian cancer e review of our experience. Eur J Gynaecol Oncol 2011;32(4):419–22. 29. Likic-Ladevic I, Kadija S, Ladevic N, et al. Urological complications after radical hysterectomy: incidence rates and predisposing factors. Vojnosanit Pregl 2007 Jun;64(6):381–4. 30. Gabriel B, Nassif J, Trompoukis P, et al. Prevalence and management of urinary tract endometriosis: a clinical case series. Urology 2011;78(6):1269–74. 31. Soriano D, Schonman R, Nadu A, et al. Multidisciplinary team approach to management of severe endometriosis affecting the ureter: long-term outcome data and treatment algorithm. J Minim Invasive Gynecol 2011;18(4):483–8. 32. Fagotti A, Costantini B, Fanfani F, et al. Risk of postoperative pelvic abscess in major gynecologic oncology surgery: one-year single-institution experience. Ann Surg Oncol 2010;17:2452–8. 33. Bouya PA, Odzebe AW, Otiobanda FG, et al. Urological complications of gynecologic surgery. Prog Urol 2011;21(12):875–8. 34. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004;240(2):205–13. 35. Fujii S, Takakura K, Matsumura N, Higuchi T, Yura S, Mandai M, et al. Anatomic identification and functional outcomes of the nerve sparing Okabayashi radical hysterectomy. Gynecol Oncol 2007;107:4–13. 36. Dursun P,AyhanA, Kuscu E.Nerve-sparing radical hysterectomy for cervical carcinoma.Crit Rev Oncol Hematol 2009;70:195–205. 37. Jackson KS, Naik R. Pelvic floor dysfunction and radical hysterectomy. Int J Gynecol Cancer 2006;16:354–63. 38. Raspagliesi F, Ditto A, Fontanelli R, Solima E, Hanozet F, Zanaboni F, et al. Nerve-sparing radical hysterectomy: a surgical technique for preserving the autonomic hypogastric nerve. Gynecol Oncol 2004;93:307–14. 39. Kato K , Tate S, Nishikimi K, Shozu M. Bladder function after modified posterior exenteration for primary gynecological cancer. Gynecologic Oncology 129;2013; 229–233. 40.Parkin DE, Davis JA, Symonds RP. Long-term bladder symptomatology following radiotherapy for cervical carcinoma. Radiother Oncol 1987;9:195 – 9.

October 2015

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Review

Obesity and breast Cancer – literature review

OBESITY AND BREAST CANCER – LITERATURE REVIEW Dr. Iuliana Pantelimon Spitalul Universitar de Urgența Elias, Secția Oncologie

Rezumat Cuvinte-cheie: neoplasm, sân, obezitate

Received: October 2015 Reviewed: October 2015 Accepted: October 2015

Această lucrare reprezintă o analiză a literaturii medicale în ceea ce privește influența obezității asupra apariției neoplasmului de sân. În cadrul acestei lucrări sunt prezentate cele mai importante studii de specialitate atât preclinice cât si clinice. În cazul studiilor preclinice , leptina are un rol important. Studiile clinice se bazează pe evaluarea răspunsului la tratament. Excesul de țesut adipos are un rol important în evoluția neoplasmului de sân atât în ceea ce privește apariția și dezvoltarea neoplasmului de sân, cât și în răspunsul la diverse tipuri de tratamente sistemice.

Introducere

Studii preclinice

În România incidența neoplasmului de sân este de 66,2/100.000 și mortalitatea de 21,6/100.000 (1) . Asociația Europeană pentru Studiul Obezității arată că prevalența obezității în Europa este de 10-25% la bărbați și 10-30% în cazul femeilor. Conform unor studii din literatura de specialitate reiese faptul că 21% din decesele în cazul neoplasmului mamar sunt datorate consumului de alcool, supraponderabilității și obezității, precum și lipsei de activitate fizică.(2) Mai multe studii epidemiologice au pus în evidență faptul că țesutul adipos în exces determină o creștere a riscului de a dezvolta neoplasm mamar și de asemenea excesul de țesut adipos pare să fie asociat cu tumori mamare cu un fenotip agresiv. (3,4) Obezitatea este asociată cu o creștere a riscului pentru cancer de sân în postmenopauză și cu o creștere a mortalității determinate de acesta. Creșterea în greutate pare să joace un rol important și complex în apariția și progresia neoplasmului de sân. În copilărie creșterea rapidă este corelată cu o menarhă precoce, acesta fiind un factor de risc cunoscut pentru apariția neoplasmului de sân. Datele din literatură sunt mai elocvente pentru influența obezității asupra apariției si evoluției neoplasmului de sân la pacientele aflate în post-menopauză, însă un studiu publicat recent în Annals of Oncology (POSH) a demonstrat efectul detrimental al obezității asupra supraviețuirii globale la paciente tinere cu vârstă sub 40 de ani. (5)

Conexiunea dintre diferitele molecule implicate în semnalizarea intercelulara sintetizate de către țesutul adipos și carcinogeneza reprezintă subiectul a numeroase studii atât preclinice, cât și clinice. Una dintre cele mai studiate adipokine implicate în biologia neoplasmului de sân este leptina. Aceasta prin intermediul receptorului său determină modificarea metabolismului energetic al celulei mamare către un metabolism caracteristic celulei de tip neoplazic, respectiv o trecere de la betaoxidarea mitocondrială la un metabolism de tip glicolitic aerob. (6) Astfel dezvoltarea neoplasmului de sân, precum și evoluția acestuia reprezintă un proces multistadial care presupune o interacțiune permanentă între celulele transformate tumoral și micromediu. Un studiu publicat de către Polyak a evidențiat rolul micromediului în dezvoltarea și progresia cancerului mamar (7). Caracteristicile legate de fenotipul celulelor maligne sunt determinate nu numai de către celulele maligne, dar și de către celulele din stroma înconjurătoare. Stroma înconjurătoare în cazul celulelor glandei mamare este reprezentată în cea mai mare parte de către adipocite. Acestea au capacitatea de a sintetiza în jur de 50 de peptide cunoscute sub numele de adipokine. Dintre acestea, cea mai cunoscută și studiată este leptina. Aceasta este produsă și de către celulele maligne mamare și este implicată în mecanisme celulare precum: invazia și migrația celulară, formarea de vase de neoangiogeneză, proliferare celulară. Leptina are un rol important în dezvoltarea neoplasmului de sân, fapt confirmat de către un studiu publicat de către Cirillo D (8). Se pare că leptina induce o amplificare a semnalizării prin intermediul receptorilor estrogenici, însă studiile arată că această adipokină influențează atât celulele mamare neoplazice estrogen pozitive, cât și pe cele estrogen negative. (9) La pacientele obeze leptina determină conversia androgenilor (androstenedionul și dehidroepiandrosteronul) la estrogeni crescând astfel concentrația aces-

Material și metode În cadrul acestei lucrării a fost efectuată o analiză a literaturii de specialitate actuale și a celor mai importante articole din baza de date PubMed în ceea Cite this article: ce privește influența excesului de țesut adipos asuPantelimon I. Obesity and breast Can- pra apariției și evoluției neoplasmului de sân. Au fost selectate articole din baza de date Pubmed focer – literature review Rom J Oncol Hematol. losind cuvinte cheie precum: cancer de sân, obezi2015; 7(2):104-106 tate, țesut adipos, leptina, adipokine.

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tora la nivel local. Acest efect apare atât la nivelul țesutului adipos, cât și la nivelul celulelor epiteliale mamare. (10) O altă proprietate a leptinei este aceea de a manifesta chemotactism pentru monocite și macrofage. Conform studiilor lui Vander celulele neoplazice prezintă o fosforilare oxidativă mitocondrială redusă și o creștere a glicolizei de la nivelul citoplasmei, un fenomen cunoscut sub numele de efect Warburg (11). Activarea unor oncogene determină de asemenea efectul Warburg. Aceste oncogene par să includă AKT1 și hipoxia inducible factor 1 alfa (HIF1A). Un studiu preclinic publicat în anul 2013 de către Qiao Zheng a investigat ipoteza conform căreia receptorul pentru leptină ar fi responsabil pentru proprietățile stem-like ale celulelor maligne mamare, proprietăți responsabile de capacitatea de metastazare a acestor celule. Această ipoteză este confirmată de către respectivul studiu preclinic. (12)

Studii clinice În prezent, există o creștere a incidenței obezității în special în țările dezvoltate. În contextul în care studiile preclinice au arătat o influență a excesului de țesut adipos asupra apariției și evoluției neoplasmului de sân, în ultimii ani au fost publicate mai multe studii clinice în vederea investigării rolului acestui factor de risc modificabil în apariția și dezvoltarea neoplasmului de sân. Amenoreea chimioindusă este considerată a fi un factor predictiv al răspunsului la tratament. Un studiu condus de Mehta a arătat că 71% din pacientele obeze devin amenoreice post chimioterapie comparativ cu 81% din pacientele care nu sunt afectate de obezitate. Altundag K și colaboratorii au propus o ipoteză conform căreia obezitatea, prin suprimarea amenoreei indusă de chimioterapie, reprezintă un factor de prognostic nefavorabil pentru pacientele aflate în premenopauza (13).

Un studiu important a arătat faptul că nivelul de supresie al estradiolului și estron sulfatului în cazul pacientelor aflate în postmenopauză tratate cu inhibitori de aromatază este mai puțin eficient la pacientele cu un indice de masă corporală crescut. (14) Unul dintre cele mai importante studii din acest domeniu este reprezentat de către studiul prospectiv britanic (POSH) publicat recent, care a urmărit evoluția a 2956 de paciente cu vârsta sub 40 de ani diagnosticate cu neoplasm de sân în perioada 2001-2007 și care a demonstrat impactul negativ al obezității asupra supraviețuirii globale. Astfel obezitatea este asociată cu o scădere a eficacității atât a chimioterapiei, cât și a hormonoterapiei la aceste paciente.

Concluzii Influența excesului de țesut adipos asupra apariției și evoluției neoplasmului de sân este evaluată în cadrul a numeroase studii preclinice și clinice. Obezitatea prin intermediul adipokinelor are un rol important în apariția și dezvoltarea neoplasmului de sân. De asemenea excesul de țesut adipos determină o scădere a eficacității tratamentelor oncologice standard. Studii ulterioare sunt necesare în vederea personalizării tratamentului la aceste paciente pentru o mai bună eficacitate. De asemenea, este necesară implementarea unor politici de sănătate publică în vederea diminuării prevalenței obezitații atât în populația general, cât și în rândul pacientelor diagnosticate cu neoplasm de sân.

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Review

Obesity and breast Cancer – literature review

References 1. WHO EUCAN Breast Cancer:estimated incidence, prevalence and mortality http://eco.iarc.fr/EUCAN/CancerOne.aspx?Cancer=46&Gender=2 2 Danaei G, Ding EL, Mozaffarian D, Taylor B, Rehm J, et al: The Preventable Causes of Death in the United States: Comparative Risk Assessment of Dietary, Lifestyle, and Metabolic Risk Factors. PLoS Med 8(1)(2011) 3 LahmanP.H. et al Body size and breast cancer risk : findings from the European Prospective Investigation into Cancer and Nutrition (EPIC) .Int.J.Cancer111,762-771(2004) 4 Renehan, A.G. , Tyson M., Egger M., Heller R..F., & Zwahlen ,M., Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies .Lancet 371, 569-578(2008) 5 E.R.Copson, R.I.Cutress,T. Maishman et al ,Obesity and the outcome of young breast cancer patientsin the UK : the Posh study, Annals of Oncology26: 101-112,2015 6. Sebastiano Ando and Ștefănia Catalano, The multifactorial role of leptin în driving breast cancer microenviroment, S.Nat. Rev. Endocrinology 8,263275(2012) 7 Polyak, K. & Kalluri R. The role of the microenviroment in mammary gland development and breast cancer Cold Spring Harb.Perspect. Biol. 2. ,a003244(2010)

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8. Cirillo D, Rachiglio A. M., La Montagna R., Giordano A. , & Normanno N , Leptin signaling in breast cancer : an overview. J. Cell. Biochem. 105, 956-964 (2008) 9. Ray A., Nkhata K.J., & Cleary M.P. Effects of leptin on human breast cancer cell lines in relationship to estrogen receptor and Her2 status.. Int. J. Oncol.30. 1499-1509 (2007) 10 Pasqualini J.R. et al Concentration of estrone and estrone sulfate and evaluation of sulfatase and aromatase activities in pre and postmenopausal breast cancer patients . J.Clin.Endocrinol. Metab.81, 1460-1464(1996) 11. Vander Heiden, M.G.,Cantley L.C.&Thomson C.B.-Understanding the Warburg effect :the metabolic requirement of cell proliferation. Science 324,1029-1033(2009 12. Qiao Zheng et al, Leptin receptor maintains cancer stem-like properties în triple negative breast cancer cells, Endocrine-Related Cancer, 20,797-808, (2013) 13. Altundaq K,Altundaq O, Morandi P, Gunduz M, “ Obesity may decrease the amenorrhea associated with chemotherapy in premenopausal breast cancer patients, Ann. Oncol.2005 Feb; 16(2):333-4 14 Folkerd EJ, Dixon JM, RenshawL, A’HernRP, Dowsett M “ Suppresion of plasma estrogen levels by letrozole and anastrozole is related to body mass index in patients with cancer”, J Clin Oncol. 2012 Aug; 30 (24) : 2977-80

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Caiet de abstracte

INTESTINAL MICROBIOTA, SMALL INTESTINAL BACTERIAL OVERGROWTH AND IMPLICATIONS IN DERMATOLOGY

Mihai Andrei Gastroenterology, Hepatology and Endoscopy Unit, Elias Emergency Hospital

Open Access Article

Abstract Keywords: intestinal microbiota, SIBO, dermatology, rosacea

Small intestinal bacterial overgrowth (SIBO) is defined by the presence of at least 100.000 colony forming units of bacterial in 1 ml of jejunal aspirate. It’s associated with many gastrointestinal pathological conditions: inflammatory bowel diseases, aclorhydria, exocrine pancreatic insufficiency, coeliac disease, post-surgical conditions and with extradigestive pathologies: acromegaly, hypothyreosis, selective IgA deficiency, lymphomas. Recent data sugest that SIBO is involved in may other diseases, especially in dermatology. When breath test is used, association of SIBO with rosacea is 40-50%. Our purpose is to review the most important data in literature regarding intestinal microbiota, small intestinal bacterial overgrowth and the connections between those and dermatological pathologies.

COMPLEXITY OF LABORATORY DIAGNOSIS IN RARE PATHOGENS CUTANEOUS INFECTIONS Violeta Corina Cristea1,2, Ramona Gîlcă1, Gabriela Neacșu1, Roxana Pricop1, Radu Sorin Serea1, Mircea Ioan Popa2 1. Laboratorul Central de Referință Synevo București Universitatea de Medicină și Farmacie “Carol Davila”, București

Open Access Article

Abstract Keywords:

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skin infections, A. Neuii, P. oryzihabitans, A. Haemlyticum, A. xylosoxidans

Skin and soft tissues infections represent an important morbidity and even mortality in hospitalized pacients. Early diagnosis and choosing the proper treatment for the microorganism involved in etiology represents of the key for terapeutical success. Given the context of infectious pathology changes from the last decades it was observed that commensal microorganisms or conditionally pathogens became fully pathogens or even emerged in immunosupressed pacients. Establishing the etiological diagnosis in these situations is possible through advanced diagnostic technologies that allow a fast and accurate identification of microorganisms that are difficult to be identify through classical systems: Actinomyces neuii, Pseudomonas oryzihabitans, Arcanobacterium haemlyticum, Achromobacter xylosoxidans. In recent specialty literature (2015), numerous studies and case presentations that describe the pathological implications of these microorganisms are published. Identification of pathological agents for these emergent infections and disseminating the information about them, play a key role in understanding the global evolution of infectious pathology.

A 5-a ediție Interdisciplinară a Conferinței HEALTH MEETING "INFECȚIILE PIELII - DE LA CERCETARE LA IMPACTUL ASUPRA SĂNĂTĂȚII PUBLICE"

COMPLEXITATEA DIAGNOSTICULUI DE LABORATOR ÎN INFECȚIILE CUTANATE DE ETIOLOGIE RARĂ Rezumat Cuvinte-cheie: infectii cutanate, A. Neuii, P. oryzihabitans, A. Haemlyticum, A. xylosoxidans

Infecțiile pielii și ale țesuturilor moi reprezintă o cauză importantă de morbiditate, uneori și de mortalitate, în cazul pacienților spitalizați. Diagnosticul precoce și alegerea tratamentului adecvat tipului de microorganism implicat în etiologie, reprezintă cheia succesului terapeutic. În contextul modificărilor patologiei infecțioase din ultimele decade s-a constatat faptul că microorganisme comensale sau condiționat patogene au devenit patogene sau chiar emergente la pacienții imunodeprimați. Stabilirea diagnosticului etiologic în aceste cazuri este posibilă prin utilizarea tehnologiilor avansate de diagnostic care permit identificarea cu acuratețe și în timp rapid a microorganismelor greu identificabile prin metode clasice: Actinomyces neuii, Pseudomonas oryzihabitans, Arcanobacterium haemolyticum, Achromobacter xylosoxidans. În literatura de specialitate recentă (2015) sunt publicate studii și numeroase prezentări de cazuri care descriu implicațiile acestor bacterii în patologie. Importanța identificării microorganismelor emergente și publicarea acestor cazuri joacă un rol important în înțelegerea evoluției globale a patologiei infecțioase.

METRICII – INSTRUMENTE DE PROMOVARE A CERCETĂRII ȘI CERCETĂTORILOR Cristina Huidiu Trainer Elsevier pentru Romania si coordonator al programului de pre-evaluare a jurnalelor in vederea indexarii in Scopus pentru Europa de Est si tarile baltice

Open Access Article This work is licensed under a Creative Commons Attribution 4.0 Unported License. The images or other third party material in Prezentarea își propune să explice pe scurt care sunt this article are included instrumentele de analiză a cercetării folosite de Elsevier, care in the article’s Creative Commons license, unless sunt metricii disponibili (SNIP, SJR, FWCI etc) pe platformele otherwise in the Elsevier de analiză a cercetării și care este utilitatea lor. Pe de o indicated credit line; if the material parte se va discuta despre avantajele pe care le oferă utilizarea is not included under the Creative Commons lor dar și limitele acestora. Metricii vor fi priviți atât din users will need perspectiva cercetătorilor cât și a editorilor de jurnale și se va license, to obtain permission prezenta modul în care aceștia pot fi folosiți pentru a descoperi from the license holder to reproduce the material. hub-uri de inovație sau direcții de dezvoltare To view a copy of this a unui domeniu. license, visit http:// creativecommons.org/ licenses/by-nc/4.0/

Rezumat Cuvinte-cheie: metrici, SNIP, SJR, FWCI, Elsevier

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Caiet de abstracte

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SOME OBSERVATIONS ABOUT ROSACEA BY DERMOSCOPY AND BACILUS SPECIES FINDINGS Alin Laurentiu Tatu University Dunarea de Jos,Faculty of Medicine and Pharmacy,Galati,Romania;

Open Access Article

Abstract Keywords: Rosacea, Dermoscopy, Spinulosis, Demodex Folliculorum, comorbidities, metabolic disorders

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Background: From clinical point of view sometime the diagnosis of Rosacea it is evident: papules, pustules, telangiectasias, flushing, blushing, phymas and ocular signs(5). Sometime we need better ways to see this condition on the skin and to detect early some infraclinical features. Dermoscopy is a useful tool in this situations for better view and recognize the specific conditions,the disease severity and also for the follow up of the treatment result.Bacillus Oleronius was isolated from Demodex Folicullorum at some Rosacea patients. Objective of the study was to find the dermoscopic features of Rosacea, some clinico dermoscopic corelations and to find some Bacillus species from Demodex Folicullorum. Methods: 138 patients with variable Rosacea clinical manifestations and subtypes were examined clinically and by dermoscopy .Demodex was identified by scraping and from 18 patients after vortexing, the sample for bacterial culture was spun two minutes and then was plated on trypticase soy agar culture media and Columbia agar with 5% sheep blood with incubation in normal atmosphere at 37ºC 24 hours. Identification was performed by microorganisms grown mass spectrometry MALDI-TOF (Matrix Assisted Laser Desorption Ionization Time-of-Flight). Results: 71,73% were women and 28,27% men ; the mean age was 44,7 years. The erithemato-telangiectatic clinical subtype was found at 42,75% of patients, with a rate of 2,68 to 1 for women to men, the papulopustular clinical subtype at 49,27% of patients,with a ratio of 5,09 to 1,the phymatous clinical subtype was found at 9,42% of patients with a ratio of 1 to 5,5 and ocular Rosacea was found at 34,05%,with a ratio of 1 to 2,91; 89,74% of the rosacea male patients had ocular symptoms. By dermoscopy I found on the face of Rosacea group the following dermoscopic features: vessels, red areas, follicular plugs, Demodex tails, scales, pustules. The most important dermoscopic sign in Rosacea is polygonal vessels, 64,49% showed red diffuse areas with or without vessels. Dermoscopy improved the detection of Demodex Folliculorum features from. 50% (with clinical spinulosis) to 62,31% of patients,of pustules from 49,27% to 56,52% and of scales from 33,33% to 39,13%. At 4 patients with Demodex Folliculorum we found the following species of Bacillus and at 2 patients with Demodex brevis we found those species of Bacillus. Conclusion: All of the patients showed clinically telangiectasias They are seen more clearly and specific with dermoscopy as red dilatated, reticular, linear, tortuous or poligonal vessels. 62,31% of the patients showed Demodex features. All patients with areas of spinulosis showed Demodex features at dermoscopy of the area and were confirmed by scraping. Dermoscopy improves the infraclinic detection of Roscea features. We did not find Bacilus oleronius. Aknowledgements: This paper is supported by the Sectoral Operational Programme Human Resources Development (SOP HRD), financed from the European Social Fund and by the Romanian Government under the contract POSDRU/159/1.5/S/137390/

A 5-a ediție Interdisciplinară a Conferinței HEALTH MEETING "INFECȚIILE PIELII - DE LA CERCETARE LA IMPACTUL ASUPRA SĂNĂTĂȚII PUBLICE"

ADULT ACNE – A PUBLIC HEALTH OPPORTUNITY FOR PREVENTING AND REDUCING ANTIBIOTIC RESISTANCE

Victor Gabriel Clătici Dermatology Department, ELIAS Emergency Universitary Hospital, Bucharest, Romania;

Open Access Article

Abstract Keywords: acne, Propionibacterium acnes, antibiotic resistance, guidelines.

Antibiotic resistance is a major concern of patients, families, and physicians, and is an important issue to consider in acne treatment with current guidelinesrecommending both acute intervention and maintenance treatment. Acne affects the vast majority of the world’s population and acne is considered now a chronic disease requiring adherence to a long duration of treatment, with antibiotics (topicals and sistemic) use for cvasimajority of patients. In the last few decades Propionibacterium acnes (P. acnes) has become resistant to many different antibiotics, making them less efficacious in treating acne. Historically, in 1976, there was no evidence of antibiotic-resistant propionibacteria on the skin of over 1000 patients with acne and the first report of resistance of P. acnes to antibiotics was in the United States in 1979, by Crawford. Resistance to antibiotic of P acnes are associated with reduced clinical response to antibiotic therapy, potential increase in pathogenicity of P. acnes and transfer of resistance to more pathogenic organisms. Resistance of P acnes to antibiotics may manifest as a reduced response, no response, or relapse and the prevalence of antibioticresistant P. acnes strains might also have implications for other potential systemic infections (a transmission of factors conferring resistance to bacteria other than P. acnes is described). The main objectives of the guidelines for acne are improvement in the care of acne patients, reduction of serious conditions and scarring, promotion of adherence and reduction the antibiotic resistance of P acnes. The Global Alliance to Improve Outcome in Acne Group recommended the following strategies to limit the development of resistance in P. acnes which included: (1) combine a topical retinoid plus an antimicrobial; (2) limit the use of antibiotics to short periods and discontinue when there is no further improvement or the improvement is only slight; (3) co-prescribe a benzoyl peroxide-containing product or use as washout; (4) oral and topical antibiotics should not be used as monotherapy; (5) concurrent use of oral and topical antibiotics should be avoided, particularly if chemically different; (6) do not switch antibiotics without adequate justification; (7) use topical retinoids for maintenance therapy, with benzoyl peroxide added for an antimicrobial effect if needed; and (8) avoid use of antibiotics for maintenance therapy.

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Caiet de abstracte

CANCER OR INFECTION? MAMMARY PATHOLOGY AT THE BOUNDARY BETWEEN BENIGN AND MALIGNANT Nicoleta CLIM1, Amelia MILULESCU1,2, Andreea Gratiana BOIANGIU1, George Alexandru FILIPESCU1,2 Obstetrics and Gynaecology Department, “Elias” Emergency University Hospital, Bucharest, Romania 2 University of Medicine and Pharmacy “Carol Davila” Bucharest, Romania

Open Access Article

Abstract Keywords: inflamatory breast cancer, examinations, breat biopsy, mastitis.

This work is licensed under a Creative Commons Attribution 4.0 Unported License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http:// creativecommons.org/ licenses/by-nc/4.0/

CANCER SAU INFECȚIE? PATOLOGIA MAMARĂ LA LIMITA ÎNTRE BENIGN ȘI MALIGN Rezumat Cuvinte-cheie: mastita carcinomatoasă, investigații, biopsie mamară, inflamație mamară

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Whether it is about lactational mastitis, breast cellulite, breast abscess, Paget’s disease of the breast, superficial thrombophlebitis, spontaneous gangrene of the breast or bite wound, a high degree of suspicion must be permanently maintained not to overlook a diagnosis of major impact on the patients lives. Inflammatory breast cancer or any other type of breast cancer presenting with infection is the matter of discussion. Several diseases can be confused with it, leading to delayed diagnosis. Clinical manifestations such as pain, diffuse erythema, tenderness, with or without systemic symptoms like fever and chills, clinical examination and laboratory tests orientate diagnosis. Persistent or recurrent symptoms after antibiotic and anti-inflammatory treatment in breast pathology apparently infectious require further investigations. Imaging examinations such as breast ultrasound, mammography or magnetic resonance imaging may be useful in the systematical differential diagnosis. Breast biopsy should be performed without delay whenever the degree of suspicion is high.

Fie că este vorba despre mastita de lactație, celulită, abces mamar, boala Paget a sânului, tromboflebita superficială, gangrena spontană a sânului sau plaga mușcata, trebuie menținut în permanență un grad înalt de suspiciune pentru a nu trece cu vederea un diagnostic cu impact major asupra vieții pacientelor. Este vorba despre mastita carcinomatoasă sau orice alt tip de cancer mamar care se prezintă cu infecție. Mai multe patologii pot fi confundate cu mastita carcinomatoasă, ducând la întarzierea stabilirii diagnosticului. Manifestările clinice precum durerea, eritemul difuz, edemul, însoțite sau nu de simptome sistemice precum febra și frisonul, examenul clinic și examenele paraclinice orientează diagnosticul. Persistența sau recurența simptomatologiei dupa tratament antibiotic si antiinflamator în patologia aparent infecțioasă a sânului necesită investigații suplimentare. Examenele imagistice, precum ecografia mamară, mamografia sau rezonanța magnetică pot fi utile în diagnosticul diferențial sistematic. Biopsia mamară trebuie practicată fără întarziere ori de câte ori gradul de suspiciune este înalt.

A 5-a ediție Interdisciplinară a Conferinței HEALTH MEETING "INFECȚIILE PIELII - DE LA CERCETARE LA IMPACTUL ASUPRA SĂNĂTĂȚII PUBLICE"

MICROBIOME AND MANAGEMENT OF ATOPIC DERMATITIS

Coman Oana Andreia 1. MD PhD, Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Medicine and Pharmacy “Carol Davila”, Bucharest, MD, Clinical Hospital of Infectious and Tropical Diseases „Dr. Victor Babeş”, Bucharest;

Open Access Article

Abstract Keywords: atopic dermatitis, human microbiome, dysbiosis, emollients, cutaneous homeostasis

Atopic dermatitis (AD) is the most common skin disease in childhood, but it has been shown that the atopic march can occur at any age. If AD cannot be controlled by topical therapy, systemic therapy should be considered. Also it is important to prevent relapses with an adequate treatment. Human microbiome is a very complex symbiotic ecosystem of commensal microorganisms, which is in homeostasis with the host, representing an entire living organism in our body. Skin microbiome includes bacteria, viruses, fungi and protozoa. Microbiome has a major impact on body functions providing antiinfectious protection, reactivity of the immune system and sometimes can augment the susceptibility to auto-inflammatory diseases. On the skin, microbiome has two ubiquitous members represented by Staphylococcus epidermidis and Propionibacterium acnes. Imbalance of skin microbiome or dysbiosis may help maintain the vicious circle of atopy. A possible favorable role of emollients was observed, regarding the relief of symptoms of atopic dermatitis, by increasing microbial diversity. Composition of these emollients improved by adding extracts of saprophytic bacteria. One such example materialized in practice isVitreoscilla filiformis bacterial lysate grown in La Roche Posay Thermal Water (Aqua Posae Filiformis). This approach allows stimulating the immune system of the skin in parallel with the regulation of cutaneous homeostasis, which would break the pathologic vicious circle of atopic dermatitis.

MICROBIOMUL CUTANAT ȘI MANAGEMENTUL DERMATITEI ATOPICE Rezumat Cuvinte-cheie: dermatita atopică, microbiom uman, disbioza, emoliente, homeostazie cutanată

This work is licensed under a Creative Commons Attribution 4.0 Unported License. The images or other Dermatita atopică (DA) reprezintă cea mai frecventă afecțiune third party material in cutanată a copilariei, însă s-a arătat că terenul atopic poate să this article are included apară la orice vârstă. Dacă DA nu poate fi controlată cu terapie in the article’s Creative Commons license, unless topică, tratamentul sistemic trebuie luat în considerare. De asemenea, este importantă prevenția recăderilor cu un tratament indicated otherwise in the credit line; if the material corespunzător. Microbiomul uman este un ecosistem foarte is not included under complex, simbiotic, al microorganismelor comensale, care se află the Creative Commons în homeostazie cu gazda, reprezentând un întreg organism viu din license, users will need to obtain permission corpul nostru. Microbiomul cutanat include bacterii, virusuri, fungi from the license holder to și protozoare. Microbiomul are un impact major asupra funcțiilor reproduce the material. To view a copy of this organismului asigurând protecția antiinfecțioasă și reactivitatea license, visit http:// sistemului imun și uneori poate favoriza predispoziția creativecommons.org/ licenses/by-nc/4.0/

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Caiet de abstracte

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pentru afecțiuni autoinflamatorii.Dezechilibrul microbiomului cutanat sau disbioza de la nivelul pielii poate contribui la menținerea cercului vicios al atopiei. S-a observat un posibil rol favorabil al unor emoliente în ameliorarea simptomatologiei din dermatita atopică, în speță pentru creșterea diversității microbiene. În consecință s-a îmbunătățit compoziția acestor emoliente prin adăugarea extractelor unor bacterii saprofite. Un astfel de exemplu concretizat în practică este lizatul bacteriei Vitreoscilla filiformis cultivat în apă termală La Roche Posay (Aqua Posae Filiformis).Această abordare permite stimularea sistemului imun al pielii în paralel cu reglarea homeostaziei cutanate, fapt care ar întrerupe cercul vicios fiziopatologic al dermatitei atopice DA poate fi văzută ca o combinație între o imunitate înnăscută și dobândită afectate care interacționează împreună în cadrul unui sistem imunitar cutanat cu funcția de barieră suboptimală .Pentru a determina extinderea și severitatea bolii se folosește scorul SCORAD (SCORing Atopic Dermatitis). Dermatologii utilizează acest scor înainte și după terminarea tratamentului pentru a determina eficacitatea acestuia. În ceea ce privește tratamentul dermatitei atopice sunt descrise o varietate largă de modalități. O combinație de terapie cu emoliente, antiinflamatorii și antimicrobiene este considerate optimă pentru majoritatea pacienților aflați în puseu acut al bolii. Emolientele constituie baza de tratament pentru formele acute și cronice de boală, dar cei mai multi pacienti necesită, de asemenea, terapie antiinflamatoare, fie cu corticosteroizi topici sau inhibitori de calcineurină topici pentru gestionarea, episoadelor acute. Dacă dermatita atopică nu poate fi controlată cu terapie topică, tratamentul sistemic trebuie luat în considerare .Pacienții cu forme severe de boală sunt, în principal, cei cu debut precoce, cei cu leziuni cutanate generalizate și cu evoluție continuă . Microbiomul uman (din greacă micro-mic, biosviață) reprezintă totalitatea microbilor și elementelor genetice ale acestora aflați în cadrul unui mediu particular. Microbiomul uman este un ecosistem. În timp ce fiecare celulă din corp care conține moștenirea genetică constituie primul genom, putem spune că microbiomul este al doilea genom. Acest microbiom este caracteristic fiecărei celule în parte, putând fi comparat cu o amprentă sau o semnătură. După naștere, pielea umană se colonizează cu diverse microorganisme care în timp formează un ecosistem complex constituit din microorganism indigene (rezidente) sau tranzitorii. Compoziția acestei comunități microbiene este diferită atât între diferiți oameni cât și în cadrul aceluiași individ, în funcție de diverși factori de mediu sau fiziologici cum ar fi vârsta, statusul hormonal, umiditatea locală, localizarea anatomică, producția de sebum și sudoare, etc. Această comunitate microbiană, denumită microbiom cutanat, include bacterii, virusuri, fungi și protozoare, iar stabilitatea sa se datorează echilibrului dintre proporția germenilor comensali și capacitatea de apărare a gazdei. Microbiomul are un impact major asupra funcțiilor organismului asigurând protecția antiinfecțioasă și reactivitatea sistemului imun și uneori poate favoriza predispoziția pentru afecțiuni autoinflamatorii. La nivel cutanat, microbiomul are 2 membri ubicuitari reprezentați de Staphylococcus epidermidis, care are capacitatea de a produce substanțe antimicrobiene și Propionibacterium acnes, care produce acizi grași cu lanț ușor sub acțiunea unor lipaze de la nivelul foliculilor pilosebacei, având în plus și proprietăți imunomodulatorii. Aceste calități sunt favorabile prin potențarea componentelor înnăscute ale gazdei de apărare imună, menținând compoziția unui microbiom cutanat sănătos. Se pare că pe pielea umană sănătoasă pot fi găsite aproape 1 miliard de bacterii pe cm2, grupate în peste 1000 de specii. Aceste specii codifică de 150 ori mai multe gene decât cele prezente în genomul uman. În ultimii ani tot mai multe studii au avut ca obiectiv cercetarea unei eventuale legături dintre microbiomul cutanat și apariția unor pusee de dermatită atopică. S-a emis ipoteza că modificarea diversității microbiene cutanate poate preceda erupțiile de atopie. Este de presupus că orice dezechilibru în microbiomul cutanat poate duce la posibilitatea apariției unor suprainfecții bacteriene la nivelul pielii. Astfel s-a constatat că înainte de erupție diversitatea florei microbiene saprofite cutanate începe să scadă, fiind urmată rapid de creșterea proporției de stafilococi, moment în care se declanșează erupția cutanată. O dată cu reducerea intensității erupției, proporția stafilococilor începe să scadă, în paralel cu creșterea diversității microbiene și revenirea microbiomului la compoziția sa normală, fiziologică. Din aceste date se poate concluziona că dezechilibrul microbiomului

A 5-a ediție Interdisciplinară a Conferinței HEALTH MEETING "INFECȚIILE PIELII - DE LA CERCETARE LA IMPACTUL ASUPRA SĂNĂTĂȚII PUBLICE"

cutanat sau disbioza de la nivelul pielii poate contribui la menținerea cercului vicios al atopiei. La pacienții atopici diversitatea microbiană de la nivelul pielii a fost mai scăzută, scăderea ei fiind direct proporțională cu severitatea dermatitei atopice. În tratamentul pacienților cu dermatită atopică s-a aplicat un emolient care s-a observat că a influențat microbiomul cutanat, prin reducerea semnificativă a tuturor stafilococilor (epidermidis, aureus, haemolyticus). S-a demonstrat pentru prima oară că tratamentul cu un emolient modifică diversitatea microbiană redusă asociată leziunilor atopice, cu reducerea proporției de stafilococi și restaurarea unei microflore diversificate (creșterea predominanței Corynebaterium sp sau Sterotrophomonas sp.). În legătură cu posibilul rol favorabil al unor emoliente în ameliorarea simptomatologiei din dermatita atopică, în speță pentru creșterea diversității microbiene, s-a pus problema îmbunătățirii compoziției acestor emoliente prin adăugarea extractelor unor bacterii saprofite. Un astfel de exemplu concretizat în practică este lizatul bacteriei Vitreoscilla filiformis cultivat în apă termală La Roche Posay, sau Aqua Posae Filiformis, care este rodul a 26 de ani de cercetare și a făcut obiectul a multorpatente de invenții În concluzie, în urma rezultatelor prezentate în multiple studii din literatura de specialitate se conturează că o abordare terapeutică rațională a dermatitei atopice ar putea consta în modularea microbiomului cutanat, cu creșterea diversității speciilor bacteriene care îl compun, în parallel cu reducerea proporției de stafilococi patogeni. Această abordare ar permite și stimularea sistemului imun al pielii în paralel cu reglarea homeostaziei cutanate, fapt care ar întrerupe cercul vicios fiziopatologic al dermatitei atopice. Nu în ultimul rând, se poate presupune că reechilibrarea microbiomului cutanat prin aplicarea unor emoliente care să conțină lizate ale unor bacterii saprofite este o abordare mult mai rațională comparativ cu utilizarea unui antibiotic clasic care distruge bacteriile neselectiv și aleator, mai ales în cazul în care nu este demonstrată prezența unei infecții cutanate.

STATUSUL DE IMUNODEFICIENȚĂ AL FEMEILOR SEROPOZITIVE - FACTOR MAJOR DE RISC ONCOGENIC HPV INDUS Mihai Mitran1, 2, Carmen Georgescu 1, Sorin Puia, Maria Comănescu 1,2 1.

Spitalul Clinic de Obstetrică-Ginecologie ”Prof. Dr. Panait Sîrbu” București 2. UMF ”Carol Davila” București

Open Access Article

Abstract Keywords: HIV, HPV, co-infection, oncogenesis

The HPV-HIV co-infection represents an aggravating circumstance for the development of the cervical neoplasia. In the co-infection cases, the axiom according to which the HPV infection is asymptomatic and self-limited does not apply due to the immunological status of immunosuppression in the case of HIV positive patients. The study carried out over a period of 1 year confirms this hypothesis, namely: - The HPV co-infection with clinical manifestation at the HIV positive patients is of 75% - The oncogene potential is much more increased than with the general population – 84,30% - The high-risk HPV roots are present in 67% of the cases A diagnosis and a precocious therapeutic measure is required with this category of patients

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Caiet de abstracte

Rezumat Cuvinte-cheie: HIV, HPV, coinfecție, oncogeneză

Confecția HPV-HIV reprezintă o circumstanță agravantă pentru dezvoltarea neoplaziei de col uterin. În cazurile de coinfecție, axioma conform căreia infecția HPV este asimptomatică și autolimitată, nu este valabilă, datorită statusului imunologic de imunosupresie la pacientele HIV pozitive. Datele studiului nostru efectuar pe o perioadă de 1 an confirmă această ipoteză și anume: - Coinfecția HPV cu exprimare clinică la pacientele HIV pozitive este de 75% - Potențialul oncogen este mult mai crescut decât în populația generală – 84,3% - Tulpinile HPV high-risk sunt prezente în 67% din cazuri Se impune la această categorie de paciente un diagnostic și o sancțiune terapeutică precoce.

NOSOCOMIAL INFECTIONS OF THE SKIN AND SOFT TISSUE IN PLASTIC SURGERY: THE ROLE OF ANTIBIOTIC PROPHYLAXIS Cristian Radu Jecan *,**, Silviu Constantin Badoiu *,**, Laura Raducu *,**, Ovidiu Stefanescu *, Adriana Neagu *, Ioana Dogaru *, Daniel Hernic *, Cristina Cozma * * Department of Plastic and Reconstructive Surgery - “Prof. Dr. Agrippa Ionescu “, Clinical Emergency Hospital, Ion Mincu St., Nr. 7, Postal Code 011356, Sect. 1, Bucharest, Romania ** ”Carol Davila” University of Medicine and Pharmacy, Bd. Eroii Sanitari, Nr. 8, Postal Code 050474, Sect. 1, Bucharest, Romania

Open Access Article

Abstract Keywords:

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nosocomial infections, antibiotic prophylaxis, surgical site infections

Health care-associated infections during hospitalisation represent an important public health issue, increasing the morbidity and mortality of the underlying disease, as well as adding to the financial burden of the case. Haematogenously spreaded infections, pneumonia, urinary tract infections and surgical site infections are most frequently described in literature. Among these, the plastic surgeon is especially faced with the latter. A surgical site infection is a post-operative infection that occurs in the part of the body where the surgery took place. Antibiotic prophylaxis, as well as other measures, is extensively used to prevent these surgical site infections. Although at present antibiotics are frequently administered, the benefit they bring to the prevention of post-surgical infections should be weighed against the risks of antibiotic treatment. A clear link has been established between excessive use of antibiotics and drug resistance. This has consequences not only for the patient (through gastro-intestinal symptoms, Clostridium difficile infection, allergic reactions), but also for the health-care setting (increased drug resistance, low antibiotic efficacy). Numerous therapeutic guidelines regarding antibiotic prophylaxis exist, but without being specifically targeted at plastic surgery. The objective of this presentation is to

A 5-a ediție Interdisciplinară a Conferinței HEALTH MEETING "INFECȚIILE PIELII - DE LA CERCETARE LA IMPACTUL ASUPRA SĂNĂTĂȚII PUBLICE"

describe and evaluate, in conformity with the principles of evidence-based medicine, the efficacy and safety of antibiotic prophylaxis in plastic surgery. A systematic research of MEDLINE, Cochrane Library and Embase databases led to the selection of relevant literature sources. It identified about 50 relevant studies regarding breast surgery, head and neck, rhinoplasty, hand surgery, skin surgery and abdominoplasty. A classification of wounds and surgical procedures including their degree of contamination is presented (clean, clean / contaminated, contaminated and dirty / infected). Results and current recommendations regarding antibiotic prophylaxis are detailed and analyzed, according to the type of surgical site involved. Systematic antibiotic prophylaxis is advised in the case of contaminated or infected surgical sites in head/neck surgery, and in clean breast surgery. It is not advised in the case of clean head/neck, hand, arm or skin surgery, or in the case of abdominoplasty.

HISTOPATHOLOGIC DIAGNOSIS OF SUBCUTANEOUS MYCOSES IN DAILY PRACTICE S. Zurac* **, C. Popp**, R. Andrei**, F. Staniceanu* **, V. Chitu* **, C. Rosculet***, A. Streinu-Cercel* *** * University of Medicine and Pharmacy Carol Davila Bucharest ** Colentina University Hospital ***Matei Bals National Institute of Infectious Disease

Open Access Article

Abstract Keywords: subcutaneous mycosis, immunosuppresion, PAS stain, Grochott stain

Introduction: Subcutaneous mycoses are infrequent lesions commonly related with immunosuppression of different causes; both clinical and pathologic appearances are inconspicuous, positive diagnosis being difficult. Usually the key of accurate diagnosis stays in adequate use of special stains (PAS, Grochott). Methods: We illustrate the spectrum of subcutaneous mycoses with several cases involving different types of fungi (mucormycetes, coccidioides imitis, aspergillus) in patients with various causes of immunodepression (corticotherapy, diabetes, autoimmune diseases, HIV infection). Results: Clinical aspects were variable and unspecific: some cases had pseudo-tumoral appearances, two of them being treated with surgical resection, other had deceptive clinical appearance suggestive of vasculitis, pyoderma gangrenosum or pemphigus vegetans, and one case had systemic involvement with severe evolution (death by septic shock and bronchopneumonia due to ocular involvement and maxillary and ethmoidal sinusitis). Histopathologic aspects included: polymorphous inflammatory infiltrate with small foci of suppurative necrosis and, occasionally, vascular lesions; microscopic diagnosis is sometimes difficult due to the scarcity of fungi identifiable even on special stains. Always, histopathologic examination should be completed with fungal cultures. Conclusion: Immunodepressed patients have a higher risk of subcutaneous mycosis, frequently with atypical presentation. A high degree of clinical and histopathological suspicion and routine use of PAS stain are very important for this diagnosis, with tremendous importance since systemic mycoses can be life threatening diseases.

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Caiet de abstracte

IMPLEMENTATION OF THERAPEUTIC PROTOCOLS IN ANOGENITAL WARTS TREATMENT Prof. Dr. Radu Vlădăreanu, Șef Lucr. Dr. Simona Vlădăreanu UMF “Carol Davila”, București

Open Access Article

Abstract Keywords: anogenital warts, clinical protocol, treatment algorithm

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Anogenital warts (Condyloma acuminata) is a common and chronic health problem among the population, with a significant impact on quality of life and health costs for the economy. In terms of pathogenesis, CA is represented by squamous epithelium benign neoplasia, highly transmissible, caused by infection with Human Papillomavirus (HPV), particularly with low-risk strains 6 and 11. Lifetime prevalence is estimated about 10%, therefore Condyloma Acuminata is considered a viral disease with the highest rate of sexual transmission. Therapeutic alternatives are mainly surgical therapy or pharmacological treatment used in hospital, or applied directly to the patient. Therapeutic methods include curettage or electrocautery and laser ablative procedures or photodynamic therapy. Topically applied substances by the doctor include mostly trichloroacetic acid, in high concentration, and cryotherapy. Regarding medical treatment administered at home by the patient, they are used mainly three groups of substances: catechins in green tea extract, podophyllotoxin (solution or cream), and imiquimod. Comparing treatment rates and relapses rate of various therapeutic options is aiming to create a clinical protocol based on available evidence, to create a treatment algorithm useful in everyday clinical practice. Invasive surgical procedures generally provide higher healing rates compared to the pharmacological treatment. Mainly referring to the curettage, the treatment rate is estimated at 89%, similar to electrocautery, the rate of which is between 61-94%. Also ablative laser treatment (23-51%) and photodynamic therapy (66-95%) reported high rates of treatment. The indication for this procedure exists, particularly in large areas and in high rate of relapses. There must be taken into account the risk of complications, namely necrosis as a result of aminolevulinic acid. For substances applied topically by the physician there are reported treatment rates of 64-88% (trichloroacetic acid) or 50-90% (cryotherapy). By comparison data, these procedures are associated with higher relapse rates in comparison with local therapy administered at home, especially sinecatehinelor. Regarding the cure rate two studies on sinecatechine (Veregen) Stockfleth et al. and Tatti S et al., showed a high treatment rate of all existing and newly emerging warts during treatment (60.7% and 57.2%). More intense local side effects in the group that received treatment with sinecatechine than the group treated with placebo were highlighted in the study by Stockfleth et al. (4.0% versus 1.9%). The occurrence of local side effects were associated with a higher treatment rate. Also, studies show the lowest relapse rate (6.5%) following treatment with sinecatechine.

A 5-a ediție Interdisciplinară a Conferinței HEALTH MEETING "INFECȚIILE PIELII - DE LA CERCETARE LA IMPACTUL ASUPRA SĂNĂTĂȚII PUBLICE"

IMPLEMENTAREA PROTOCOALELOR TERAPEUTICE ÎN TRATAMENTUL CONDILOMATOZEI ANOGENITALE Rezumat Cuvinte-cheie: veruci anogenitale, protocol clinic, algoritm terapeutic

Verucile anogenitale (Condyloma acuminata) reprezintă o problemă frecventă şi cronică de sănătate în rândul populaţiei, cu un impact semnificativ asupra calităţii vieţii şi costuri importante pentru economia sănătăţii. Din punct de vedere al patogenezei, CA este reprezentată de neoplazii benigne ale epiteliului scuamos, cu grad ridicat de transmisibilitate, cauzate de infecţia cu Human Papilomavirus (HPV), în special cu tulpinile cu risc scazut 6 şi 11. Prevalenţa pe parcursul vieţii este estimată la aproximativ 10%, astfel ca Condilomatoza Acuminata este considerată o afecţiunea virală cu cea mai ridicată rată de transmisie pe cale sexuală. Alternativele terapeutice utilizate sunt în principal de tip chirurgical sau medicamentos, utilizate în ambulatorul de specialitate sau aplicate de către pacient direct. Metodele terapeutice includ chiuretarea sau electrocauterizarea, precum şi proceduri ablative cu laser sau terapie fotodinamică. Substanțele aplicate local de către medic includ mai ales acidul tricloracetic, cu concentraţie ridicată, precum şi crioterapia. În ceea ce priveşte tratamentul medicamentos administrat la domiciliu de către pacient, sunt utilizate în principal trei grupe de substanţe: catehine din extract de ceai verde, podofilotoxină sub formă de soluţie sau de cremă, precum şi imiquimod. Compararea ratelor de vindecare şi de recidivă a diferitelor opţiuni terapeutice are rolul de a crea o bază decizională bazată pe evidenţele clinice disponibile, pentru a crea un algoritm de tratament util în activitatea clinică cotidiană. Procedurile chirurgicale invazive asigură în general rate mai ridicate de vindecare în comparaţie cu terapiile medicamentoase. În principal ne referim la chiuretare, cu o rată de vindecare evaluată la 89%, similară cu a electrocauterizării, a cărei rată este intre 61-94 %. Şi pentru tratamentul cu laser ablativ (23-52%, respectiv 81%) şi terapia fotodinamică (66-95%) sunt raportate rate ridicate de vindecare. Indicaţia pentru această procedură există, în special în cazurile pe zone extinse şi recidivante. Trebuie luat în calcul riscul de apariţie a complicațiilor, respectiv a necrozelor, ca urmare a acidului aminolevulinic. Pentru substanțele aplicate local de către medic sunt raportate rate de vindecare de 64-88% (acid tricloracetic) respectiv 50-90% (crioterapie). This work is Prin comparația datelor, aceste proceduri sunt asociate cu rate de licensed under a Creative recidivă superioare terapiilor locale administrate la domiciliu, în Commons Attribution 4.0 Unported License. special ale sinecatehinelor. Referitor la rata de vindecare, două The images or other third party material in studii efectuate pe sinecatechine (Veregen), Stockfleth et al. și this article are included Tatti S et al.,au prezentat o rată ridicată de vindecare a tuturor in the article’s Creative condiloamelor existente și nou apărute pe durata tratamentului Commons license, unless (60.7%, respectiv 57.2 % ). Efecte secundare locale mai intense în indicated otherwise in the cadrul grupului care a beneficiat de tratamentul cu sinecatechine, credit line; if the material is not included under precum şi al celui tratat cu preparate placebo au fost evidenţiate the Creative Commons în studiul efectuat de Stockfleth et al. (4.0% versus 1.9 %). Apariţia license, users will need to obtain permission efectelor secundare locale a fost asociată cu o rată mai ridicată from the license holder to de vindecare. Totodată, studiile efectuate demonstrează cea reproduce the material. To view a copy of this mai scăzută rată de recidivă (6.5%) în urma tratamentului cu license, visit http:// sinecatechine. creativecommons.org/ licenses/by-nc/4.0/

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Caiet de abstracte

INFECTIOUS FACTORS IN SKIN CANCERS

Prof. Dr. Solovan Caius Dermatologie , Universitatea de Medicina si Farmacie „Victor Babes”, Timisoara

Open Access Article

Abstract In the present presentation we performed a review of the relation between microbioma and immune function of the skin, of the pathways which promote and develope skin neoplasia. All these together define the tumor as an organ. We tried to exemplify those aspects by models from skin and general pathology. We underlined with evidence the more and more precise relationship between the genomic sequence and the promoting respectiv the progression facts of the neoplasia process

Keywords: microboma, skin immunology, skin neoplasia

FACTORII INFECȚIOȘI ÎN CANCERELE CUTANATE Rezumat Cuvinte-cheie: This work is licensed under a Creative Commons Attribution 4.0 Unported License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http:// creativecommons.org/ licenses/by-nc/4.0/

microbiom, imunologie cutanata, neoplazii cutanate

În lucrarea de față ne-am propus o trecere în revistă a relației între microbiom și funcția imună a pielii, a circuitelor care stau la baza inițierii și progresiunii neoplazice cutanate, fapte care definesc tumora ca și un organ. Am încercat sa exemplificăm aceste aspecte cu modele din patologia cutanată dar și generală. Am scos în evidență cu date relația tot mai precizată între secvența genomică și procesul de inițiere respectiv progresie a procesului neoplazic.

BOLILE CU TRANSMITERE SEXUALĂ ÎN MEDICINA SEXUALITĂȚII

Radu Mihalcaa, Andreea Ruxandra Albub, Endocrinolog-Androlog, Sanamed Hospital, București, Romania b Ginecolog, Spitalul Universitar de Urgență, București, Romania

Open Access Article

Rezumat Cuvinte-cheie: BTS, patologii, infertilitate, disfuncții sexuale

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Bolile cu transmitere sexuală (BTS) sunt între cele mai vechi patologii studiate în medicina umană. Importanța acestora de-a lungul istoriei a fost foarte mare. Prevalanța actuală a BTS la tineri este de circa 15%, cu o incidență anuală la nivel mondial de circa 19.000.000 de cazuri. În secolul XXI BTS nu mai sunt asociate cu mortalitatea semnificativă din trecut dar continuă să reprezinte o problemă de sanătate publică datorită prevalenței și a impactului asupra calității vieții pacientului. Infertilitatea și disfuncțiile sexuale sunt consecințe frecvente ale BTS, prevenția fiind în acest caz modalitatea principală de abordare.

A 5-a ediție Interdisciplinară a Conferinței HEALTH MEETING "INFECȚIILE PIELII - DE LA CERCETARE LA IMPACTUL ASUPRA SĂNĂTĂȚII PUBLICE"

CIRCUITUL, COLECTAREA ȘI CALITATEA DATELOR DIN SISTEMUL DE SUPRAVEGHERE AL ITS LA NIVEL NAȚIONAL

Dr. Viorica Gheorghiu

Centrul Național de Supraveghere și Control al bolilor Transmisibile

Open Access Article

Rezumat Cuvinte-cheie: boli cu transmitere sexuala,

sifilis, ITS

În România bolile cu transmitere sexuală reprezintă înca o problemă de Sănătate publică, iar pentru sifilis ne aflăm în topul țărilor cu cea mai mare incidență în cadrul Uniunii Europene. Sistemul de supraveghere al infecțiilor cu transmitere sexuală la nivel național este legalizat prin ordinul MS 1342/noiembrie 2013 și intrat în vigoare de la 1 noiembrie 2014. Dintre bolile cu transmitere sexuală, sifilisul, gonoreea și infecția genitală cu Chlamydia Trachomatis sunt obligatorii. La nivel national, datele colectate prin reteua de boli dermatovenerice (D-V)sunt centralizate de Direcțiile de Sănătate Publică județene și transmise la Centrul National de Supraveghere și Control al Bolilor Transmisibile. Cu toate că modalitatea de colectare a datelor a fost simplificată iar fișa de declarare a cazului nou de ITS este disponibilă și în format electronic, există încă multe lacune în notificarea acestor afecțiuni. Nerespectarea cadrului legal este recunoscută și acceptată de către specialiștii dermato-venerologi ca una dintre cauzele principale ale subraportării. Medicii de alte specialități (mai ales ginecologie) care au dreptul sa diagnosticheze și să trateze cazurile de infecție cu Chlamydia ignoră total obligația raportării acestora la nivel național. Pentru îmbunătățirea raportării și a supravegherii ITS la nivel național se impune o mai bună colaborare, comunicare și instruire între specialiștii retelei D-V, alți specialiști și epidemiologi de la nivelul DSP județene.

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TALON DE ABONAMENT Revistă creditată de CMR cu 5 credite EMC pentru abonamentele plătite

Doresc să mă abonez la qA bonament pentru 1 an 4 numere ale revistei qA bonament pentru 2 ani 8 numere ale revistei

90 RON 160 RON

Nume:................................................................................... Prenume: ............................................................................... Dna Dl Dra Adresă domiciliu: ..................................................................................................................................................................... Municipiu: ........................................................................ Sect.: ................ Judeţ:............................................................ Oraş:................................................................. Comună: ...................................................................................................... Cod poştal: ............................................... Telefon: ............................................................................................................... Specialitate ................................................................................................................................................................................ student rezident medic specialist medic primar Competenţă ............................................................................... Denumire instituţie: ....................................................... Domeniu de activitate: Privat Public Secţie: ................................................................................................. Funcţie: ...................................................................... Specialitate: ................................................................. Adresă instituţie: ............................................................................ .................................................... Municipiu: ....................................................Sect.: ........... Judeţ:................................. Oraş:................................................................. Comună: ...................................................................................................... Cod poştal: ............................................... Telefon: .......................................... Mobil: ...................................................... E-mail: ........................................................................ Web: ................................................................................................... CUI instituţie: Plătitor de TVA: da nu Factură - vă rugăm să completaţi cu coordonatele necesare emiterii facturii: Denumire persoană: ...................................................... Denumire instituţie: .................................................................. Adresa pentru primirea revistelor MEDIA SYSTEMS COMMUNICATION: Domiciliu Instituţie Data:

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După completare, vă rugăm să trimiteţi talonul însoţit de dovada efectuării plăţii la adresa: MEDIA SYSTEMS COMMUNICATION S.R.L., Calea Rahovei nr. 266-268, corp 2, etaj 2, camerele 22-23, Sector 5, Bucureşti, cod poştal 050912, prin fax (031) 432.82.30 sau scanate prin e-mail la office@msc-ro.com. Mulţumim!

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Plata abonamentului se va efectua prin mandat poştal sau prin ordin de plată pe coordonatele: MEDIA SYSTEMS COMMUNICATION S.R.L., Calea Rahovei nr. 266-268, corp 2, etaj 2, camerele 22-23, Sector 5, Bucureşti, cod poştal 050912, CUI RO31922876, J40/8111/2013. Cont RON IBAN: RO05BACX0000000912742000, deschis la Unicredit Țiriac Bank, Sucursala Rahova.

Doresc să primesc o copie a facturii abonamentului: q Da, la adresa de e-mail: ..................................................................... q Da, la fax: .....................................................................

SC MEDIA SYSTEMS COMMUNICATION cu sediul în București, Calea Rahovei nr. 266-268, corp 2, etaj 2, camerele 22-23, CUI RO31922876, J40/8111/2013 prelucrează datele cu caracter personal furnizate de dumneavoastră prin acest document în scopul actualizării bazei de date. Pe viitor, datele menționate ne permit să vă ţinem la curent cu activitatea noastră. În cazul în care nu doriţi această informare, bifaţi

Conform Legii nr. 677/2001, beneficiaţi de dreptul de acces, de intervenţie asupra datelor, dreptul de a nu fi supus unei decizii individuale. Aveţi dreptul să vă opuneţi prelucrării datelor personale care vă privesc şi să solicitaţi ştergerea datelor. Pentru exercitarea acestor drepturi, vă puteţi adresa cu o cerere scrisă, datată şi semnată la sediul social din Calea Rahovei nr. 266-268 corp 2 etaj 2 camerele 22-23, București. De asemenea, vă este recunoscut dreptul de a vă adresa justiţiei. Media Systems Communication este înregistrată la Autoritatea Națională de Supraveghere a Prelucrării Datelor cu Caracter Personal sub numărul 29878/7.11.2013.

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