Aetiology, clinical presentatio n and outcome of upper gastrointestinal 2009 by lawjuris

AETIOLOGY, CLINICAL PRESENTATION AND OUTCOME OF UPPER GASTROINTESTINAL BLEEDING A STUDY OF 100 CASES INTRODUCTION Upper gastro intestinal haemorrhage is a common & serious medical as well as surgical emergency. The most common presenting features of upper gastro intestinal haemorrhage are haematemesis & maelena1. Haematemesis indicates an upper gastro intestinal source of bleeding (above the ligament of treitz)". Haematemesis may be red with clots when bleeding is profuse or black (coffee ground) when less severe. Syncope may occur and it is due to hypotension from intravascular volume depletion. Symptoms of anemia suggest chronic bleeding.3 Melaena is the term used to describe the passage of black, foul smelling, tarry, stools containing altered blood.3 Melaena indicates that blood has been present in upper gastro intestinal tract for at least 14 hours 2. Melaena develops after as little as 50-100 ml blood loss in the upper gastro intestinal tract. The characteristic appearance is result of action of digestive enzymes and bacteria upon haemoglobin 3. In USA approximately 115 patients per 100,000 populations are hospitalized each year for the episode of upper gastro intestinal haemorrhage 4. This leads to approximately 250,000 new hospital admissions per year 5. Among them 3362% are due to peptic ulceration, 4-31% from varices, 3-11% due to gastroduodenal erosion and 1-4% from malignancy2 .

Mortality from bleeding increases with age 6. Mortality of patient admitted to hospital following gastro intestinal haemorrhage is about 10% 3. The mortality rate for patients under 60 years of age without any organ failure or malignancy is <1%2. However mortality from a first bleed from varices is around 50% 7 and most8 survivors rebleed with an inpatient mortality of about 30%8. As an immediate management of all cases of recent (within 48 hours) significant gastro intestinal haemorrhage should be admitted into hospital9. Upper GI endoscopy is the best choice in patient with upper gastro intestinal haemorrhage. Emergency endoscopy enables diagnosis as well as appropriate therapy & provides important prognostic significance. With the introduction of widespread fibre optic endoscopy service it became clear that many minor mucosal lesions had been missed when diagnosis of the cause of bleeding had relied on clinical and radiological means. From different studies in home and abroad leading causes of upper Gl haemorrhage are-7 1. Duodenal ulcer. 2. Gastric erosion. 3. Gastric ulcer. 4. Ruptured esophageal varices. 5. Gastric cancers. 6. Miscellaneous.

It is sometimes very difficult to find out the causes of UGIB from the list of numerous aetiology, which are already mentioned, ranges from curable peptic ulcer disease to killer disease like carcinoma.

Considering the diverse aetiology and its effect which can be minimal to fatal, all cases of recent (within 48 hours) significant gastrointestinal bleeding should be admitted to hospital, the causes of UGIB should be identified as early as possible and treated promptly. In approximately 80% of patients presenting with acute UGIB, bleeding ceases spontaneously and does not recur 10. Such cases are often initially treated with intravenous crystalloid or colloid solution & blood is given to restore blood pressure when patients is shocked or when haemoglobin concentration is less then 100g per liter before detecting aetiology 3. Knowledge regarding common causes of UGIB in our country is therefore necessary because it is an important problem in our hospital where we deal with these patients frequently. In Bangladesh endoscope is now available in almost every medical college hospital, in some private clinics and diagnostic centers of the country. For detection of causes of upper GIT bleeding there is no alternative for actual visualization of bleeding points by endoscopy. This will not only solve some of our problems but also provide with an opportunity to make an appraisal of UGIB. However endoscopy is not available in district and upazila hospital where often our junior doctors manage the patients. Considering all these, the study which has been carried out in 100 patients will help create awareness among all level of medical practitioners and enhance prompt diagnosis or at least early referral. That may reduce sufferings and cost of expensive tests for the poor patient of this country and our doctor can even appropriately manage patients with upper GIT bleeding outside tertiary hospital.

KNOWLEDGE ABOUT UPPER GASTRO-INTESTINAL HAEMORRHAGE Most patient with haematemesis and melaena present in the hospital as primary bleeder while some patients (secondary bleeders) who are critically ill develop haematemesis and melaena in the hospital. The mortality is very high in patient with bleeding that develops in the hospital and this is usually a result of systemic diseases. 12 Haematemesis means the vomiting of fresh blood, blood with clots, or blood which has been subjected to digestion by gastric juices. The presence of fresh blood in the vomitus implies recent haemorrhage, often moderately large volume, from the upper alimentary tract, where as the presence of â&#x20AC;&#x2DC;coffee groundâ&#x20AC;&#x2122; vomit suggests UGI bleeding, sometimes of smaller volume, over a more prolonged period13. Melaena is the term used to describe passage of black tarry stool containing altered blood; this is usually due to bleeding from upper GI tract, although haemorrhage from the right side of the colon is occasionally responsible. The characteristic appearance is the result of action of digestive enzymes and bacteria upon haemoglobin. Such stools are tarrying ("sticky") and have a characteristic odour.14 In case of bleeding from the stomach, the process is initiated by acid pepsin at the initial site. Other factors influencing the production of tarry stool are: 1.

Site of bleeding

Amount of bleeding

Rapidity of bleeding

Intestinal transit time

Bacterial breakdown of haemoglobin in the intestine.

Haematemesis results from a combination of large amount of blood filling the stomach together with the urge to vomit. So haematemesis generally indicates a more severe bleeding episode than melaena. On the other hand, at least 60ml. blood is required in the upper GIT to produce a single black stool. Melaena usually denotes bleeding from the esophagus, stomach or duodenum but lesion in the jejunum, ileum and even ascending colon may occasionally because melaena provided the gastrointestinal transit time is sufficiently prolonged. Haematochezia is the passage of bright red blood per rectum, generally signifies bleeding from a source distal to the ligament of treitz. However, brisk proximal bleeding can cause haematochezia due to rapid transit.

AETIOLOGY OF UPPER GASTROINTESTINAL BLEEDING Haematemesis and melaena, the commonest presentation of upper GI haemorrhage results from a variety of causes: Common Causes: 1. Peptic Ulcer -Duodenal ulcer and Gastric ulcer 2. 3. 4. 5. 6.

Erosive gastritis Varices or portal hypertension Reflux oesophagitis Mallory-Weiss tear Vascular malformation

Uncommon causes: 1. Gastric carcinoma, lymphoma, polyp and other gastric tumour. 2. Duodenal and jejunal diverticuli. 3. Aorto-duodenal fistula 4. Primary aortoesophageal fistula 5. Haemobilia following hepatic surgery or trauma

6. Primary blood dyscrasias. 7. Vasculitis. 8. Hereditary hemorrhagic telangiectasia 9. Connective tissue disorder: eg. PAN. 15 10. Uraemia 11. No sources identified Peptic ulcer is the common cause of upper GI bleeding. In Greece a study conducted in 1534 patientsâ&#x20AC;&#x2122; shows that peptic ulcer (67%) is the main cause of upper GI bleeding.16 In a study in Thailand on 5000 patients of haematemesis and melaena showed peptic ulcer-51.24%, acute mucosal erosions-31.6 %, cancerous bleeding1.66%, gastric polyp-28%, normal study-2.46%, Another study in Jerusalem showed DU-16.9%, esophageal varices-7.5%, erosive gastritis-8,2%, esophagitis7.5%.17 In one study of American society of gastro endoscopy, shows usually the frequency of haemorrhage is directly related to the duration of disease. However, there is a greater tendency to bleed during the first year 84% as opposed to 5.4%, 5% & 5.9% in subsequent years respectively. In national American Society of Gastroenterology (ASGE) survey on upper GIT involving 2225 patients, six pathological entities were responsible for most bleeding episode. These include in decreasing order of frequency duodenal & gastric ulcer, acute gastritis, oesophageal varices, esophagitis and Mallory-Weiss tear. 19 acute gastric erosions & gastritis have become increasingly common and assumed an important position among the causes of upper GI haemorrhage. The study of gastritis has been widened by the use of the fibreoptic endoscope. Massive haematemesis and /or melaena are caused by gastritis in 21.5%, acute haemorrhagic erosive gastritis in 18.5% of the hospitalized patients for upper GI

haemorrhage. Massive bleeding in patients with cirrhosis of liver may be due to gastritis and is 22%. Similarly variceal bleeding is much more common, In a survey in England, Scotland & Sweden bleeding from varices was 7.3% but in USA it was 11.2%.20 The proportion of cases of variceal bleeding is greater in countries where alcohol consumption is higher and where hepatitis B virus infection is common. In recent years UGI bleeding has been associated with the ingestion of NSAIDs taken for arthritis or local motor disorders. Among the patients bleeding from peptic ulceration about 35% had ingested NSAIDs in the week prior to presentation and the majority (84%) over the age 60 year . 15 A study of Somerville K 20has shown that 35-55% of elderly patients admitted with upper GI bleeding have taken NSAIDs. Up to 22% of bleeding episode may be due to these drugs with a mortality of 10%. Vascular anomalies are found throughout the gastrointestinal tract may the source of acute upper GI bleed. The account for about 7% of causes of bleeding vascular ectasias (angiodysplasia) has a bright red stellete appearance. They may be part of systemic condition (hereditary hemorrhagic telangiectasiaCREST syndrome) 21. In a small but definite proportion of cases no identifiable source of bleeding is found are also have some interest? Upper gastrointestinal bleeding with no identifiable cause: 1. Lesion missed: Site obscured (blood clots etc) Gastric fundus not fully examined 2. Inexperienced operator 3. Lesion healed 4. Intermittent bleeding

5. Delay in investigation 6. Site not considered / reached: Nasopharynx Second part of duodenum Biliary tract Pancreas PATHOPHYSIOLOGY Ulcer: Ulcers are defined as disruption of mucosa integrity of the stomach or duodenum leading to local defect or excavation due to active inflammation. Ulcer occurs in the stomach or duodenum often chronic in nature. 22

Peptic ulcer: Peptic ulcers are chronic, most often solitary lesions that occur in any portion of the gastrointestinal tract exposed to the aggressive action of acidpepsin juices.22 Distinctive features of peptic ulcer: 23 1. Usually a single lesion. 2. Tends to be less than 4 cm in diameter. 3. By definition penetrates muscular is mucosa; may perforate gastric wall. 4.Is

frequently

recurrent,

with

intermittent

healing.

5. Is located in the following sites, with decreasing frequency; I. Duodenum, first part, ii. Stomach, usually antrum. iii. Within barret's mucosa. Iv. In the margins of a gastroenterostomy (stomal ulcer) V. In the duodenum, stomach, or jejunum of patients with Zollinger-Ellison syndrome. vi.

Within or adjacent to a meckel's diverticulum that contains ectopic

gastric mucosa.

Morphology: Ninty eight percent of peptic ulcers are located in the first part of duodenum, or in the stomach in a ratio 4:1, most duodenal ulcer is in the first part of the duodenum within a few cm of pyloric ring. The anterior wall of the duodenum is more often affected than the posterior wall. Gastric ulcers are predominantly located in the lesser curvature in and around the border zone between the corpus and the antral mucosa. Less frequently they may occur on the anterior or posterior wall of the greater curvature of the stomach. In 10 to 20% of patients with gastric ulceration, there may be a coexistent duodenal ulcer. Irrespective of the site, chronic peptic ulcer has a fairly standard gross appearance. Small lesion less than 0.3 cm are more likely to be shallow erosion, those greater than 0.6 cm are likely to be ulcer. Although more than 50% peptic ulcers have a diameter of less than 2 cm, about 10% of benign ulcer greater than 4 cm. Even carcinomatous ulcer is may be less than 4 cm in size. So, size does not differentiate benign from a malignant ulcer. Histological appearance: The histological appearance varies from active necrosis to chronic inflammation and scarring to healing. In active ulcers with ongoing necrosis, four zones are demonstrable: 1. The base and margins have a superficial thin layer of necrotic: fibrinoid debris not visible to the naked eye. 2. Beneath this layer is the zone of a nonspecific inflammatory infiltrate with neutrophils predominating. 3. In the deeper layers, especially in the base of the ulcer, there is an active granulation tissue infiltrated with mononuclear leukocytes. 4. The granulation rests on a more solid fibrous or collagenous scar.

GASTRIC PHYSIOLOGY RELATED TO PEPTIC ULCER: A. Aggressive factors:Acid and pepsin: The gastric mucosa has an extraordinary capacity to secrete acid. The parietal cells scattered along the course of the mucosal glands (oxyntic mucosa) of the body and fundus of the stomach secretes HCL by a process involving oxdative phosphorylation. The estimated concentration of HCL by parietal cells is approximately 160 ml. For each H+ Secreted into lumen, one HCO3- is released into the gastric venous circulation, accounting for alkaline tide, reflection of gastric HCL secretion. The final step in H+ secretion is accompanied by a proton pump mechanism involving specific hydrogen potassium adenosine triphosphatase (H+K+ ATPase) located in the apical micro villous1 membrane and tubulovesicular apparatus. The major physiological stimulus for gastric acid secretion is ingestion of food. Traditionally regulation of gastric acid secretion has been classified into three phases. Phases: Cephalic, gastric and intestinal. Cephalic phase: Is initated by the sight of taste, smell, chewing & swallowing of palatable food. This phase is largely mediated by direct vagal stimulation of gastric release.

Gastric Phase: Induced by food in the stomach. Intestinal Phase: Is initiated when food containing digested protein enters the proximal small intestine. The stimulation of acid secretion that occurs at that time is thought to be related to elaboration in the small intestine of a polypeptide quite distinct from gastrin. The proteolysis effect of pepsin in concert with the corrosive properties of secreted gastric acid contributes to the tissue injury that produce peptic ulcer. Gastric acid catalyzes the cleavage of inactive pepsinogen molecules, converting them to proteolytically active pepsins and also provides the low P H required for pepsin activity. B. Mucosal Defense: The mechanism by which the normal stomach & duodenum resists the corrosive effects of acid & pepsin (i.e. the mechanism of mucosal resistance to injury or mucosal defense) have not been defined clearly. However, a variety of factors have been identified that contribute to or compromises mucosal defense. Factors areGastric Mucus Bicarbonate (HCO3~) Prostaglandin Epithelial barrier Mucosal blood flow Neural & muscular component.

Gastric mucus: Secreted by mucous cells of gastric mucosal epithelium and gastric gland is important in mucosal defense and in preventing peptic ulceration. Mucus secretion is stimulated by mechanical or chemical irritation and by cholinergic stimulation. Gastric mucus is present in two phases: In a stable phase; in gastric juice & as in insoluble mucus gel layer, approximately 0.2 mm thick, which coats the mucosal surface of the stomach. When intact this mucus gel serves as a unstirred water layer that slows ionic diffusion but more impermeable to penetration macromolecule such as pepsins (Mol.wt 34,000). Gel thickness is increased by prostaglandin E & reduced by aspirin & other NSAIDs. Gastric mucus glycoproteins also contain antigenic determinants used to classify ABO blood group substance. Approximately 3/4th of the population secretes gastric juice containing these ABO substances. Such individuals are referred to as secretors. Bicarbonate (HCO3): Non parietal gastric epithelial cells secrete HCO3- ions into mucus gel which help create a microenvironment with a substantial H + ion gradient ranging from PH 1 to 2 in the luminal side of the gel layer to PH 6 to 7 in the zone in contact with gastric mucosal cells. As an unstirred water layer, the mucus gel slows the diffusion of H+ toward the gastric mucosal surface allowing buffering by HCO 3with the gel gastric HCO3- is stimulated by calcium, certain prostaglandin of E&F series, cholinergic agents & dibutyryl cyclic guanidine monophosphate. Aspirin & NSAIDs, acetazolamide, adrenergic agents inhibit it. Epithelial barrier (Tight junction): Normally the luminal surfaces and intercellular tight millions of the gastric epithelial cells create a gastric mucosal barrier that is almost completely impermeable to diffusion of the H+ from the lumen. There barrier can be interrupted by bile acids, ethanol, & weak organic acids, permitting H+ to

diffuse into the gastric tissue. The result may be cell injury and release of histamine from mast cells, further stimulation of acid secretion, and damage to small blood vessels, mucosal haemorrhage, and erosion or ulceration. Mucosal blood flow: The gastric mucosa has a rich blood supply consisting of extensively arborising capillaries. A rich blood flow is necessary to provide O2, HCO3-, and nutrients to epithelial cells and to remove back diffused acids. Mucosal blood flow is regulated by local vasoactive mediators, particularly endogenous nitric oxide (generated by endothelial cells), prostaglandins, and neuropeptides, increased blood flow occurs simultaneously with stimulation of acid secretion. Gastric blood flow may be adversely affected by severe medical or surgical stress exogenous agents such as aspirin & alcohol and entry into the lamina propriety of luminal agents such as acid and pepsin. Prostaglandin: Prostaglandins are abundant in the gastric mucosa. Administration to animals of various prostaglandins, particularly those of E series has been shown to prevent mucosal injury caused by a wide variety of agents. Endogenous prostaglandins stimulate secretion of gastric mucus, gastric and duodenal HCO 3- . They participate in the maintenance of gastric mucosal blood flow and of the integrity of the gastric mucosal barrier and promote epithelial cell renewal in response to mucosal injury.24 Neural and muscular component: Afferent neurons within the mucosa of the stomach and perhaps the duodenum can trigger a protective reflex vasodilatation when toxins or acid breach the epithelial barrier. In addition muscular is mucosa may serve to limit the injury. Superficial damage limited to the mucosa can heal within hours to days. When

damage extends in the sub mucosa, a minimum of several weeks is required for complete healing. Pathogenesis of peptic ulcer 25: 1. Peptic

ulcers

are

produced

imbalance

between

the

gastroduodenal defense mechanisms and the damaging forces. 2. Some level of acid pepsin secretion is requisite for the development of duodenal & gastric ulcreation. 3. For duodenal ulcers, major causal influences appear to be exposure of gastroduodenal mucosa to excessive amounts of acid & pepsin. 4. For Gastric ulcers, the major causal influence appears to be some break down in gastric mucosal defense against acid & pepsin. Duodenal ulcers: In general, duodenal ulcer patients have: 1) Increased capacity to secrete acid & pepsin 2) Increased responsiveness to stimuli of acid secretion and 3) In some patients with DU, there is too rapid gastric emptying exposing the duodenal mucosa to an excessive acid load.

Gastric Ulcer: GU patients as a group have acid secretion rate that is normal or reduced compared with non ulcer subjects, although true achlorhydria almost rever occurs with benign GU. It is suggested from different data that is existence of some primary defect in gastric mucosal resistance likeo an increased tendency of back diffusion of H + augmenting some derangement in the gastric mucosal barrier. o Frequent association of chronic antral gastritis with the ulcer. Gastritis is present in association with ulceration in most cases. o Gastritis persists even after the ulcer heals, suggesting that gastritis is primary and gastric ulcer secondary. Helicobacter pylori in gastroduodenal disease: Helicobacter pylori colonize the gastric mucosa. It is found primarily in the deeper positions of the mucus gel that coats the gastric mucosa and between the mucus gel layer and apical surfaces of the gastric mucosal epithelial cells. H pylori may adhere to the luminal surfaces of gastric epithelial cells but does not invade the gastric mucosa. H pylori produce a variety of proteins that appear to mediate or facilitate its damaging effect on the gastric mucosa. Urease produced by H pylori catalyzes the hydrolysis of urea to ammonia and carbon dioxide. Hydroxide ions generated by equilibration of water with ammonia may contribute to gastric mucosal epithelial damage. H.pylori produces surface proteins that are chemotactic for human neutophils and monocytes and secrets platelet activating factors which is also pro inflammatory. H pylori activate monocots which express HLA-DR & IL2 receptors on their cell surfaces and produce superoxides IL1 and TNF. This organism also produces protease and phospholipase, which degrade the glycoprotein lipid complex of the mucus gel layer, this activity reduces the thickness and viscosity of the mucus gel layer overlying the gastric mucosal epithelial cell layer.26'27

Risk Factors for peptic Ulcer: Dietary factors: Dyspepsia may be caused by certain foods, spices beverages. Tovey in 1979,

reported that DU is more in rice eating belt in south India compared

with wheat eating areas in the north and there is no geographic correlation between habitual consumption of hot spices and the high prevalence of DU in some case. Alcohol: Alcohol has not been proved to cause peptic ulceration directly. But according to Hudson30 possibly alcohol ingestion has got some relationship with development of erosive mucosal disease in the stomach leading to bleeding. Drugs: Aspirin and other NSAIDs cause acute gastric mucosal damage and precipitate upper GI bleeding. Cigarette smoking: Cigarette smoking has been associated with an increased incidence of DU, a Decreased response to DU therapy and an increased mortality from DU. Cigarette smoking impairs healing and favours recurrence and so is suspected of being ulcerogenic, possibly by suppression of mucosal prostaglandin synthesis29.

Association with blood groups, antigens HLA and secretary status: Patients with DU have an increased frequency of blood group O and of the non secretary status (absence of secretion of blood group) ABO antigens into the gastric juice), but these association are weak. More over the association with blood group O may relate to preferential binding of group O antigens to H pylori. An increased incidence of HLA-B5 antigen has been reported in white male subjects with DU. Association of peptic ulcer with some other disease: 1. Gastrinoma and MEN type- 1 2. Chronic obstructive pulmonary disease. 3. CRF. 4. Cirrhosis of liver 5. Alpha 1-antitrypsin deficiency 6. Systemic mastocytosis. 7. Basophilic leukaemia. Acute erosion and stress ulceration: Definition: 23 Focal acutely developing gastric mucosal defects may appear following severe stress, whatever its nature-hence the designation stress ulcer. Stress erosions and ulcer are most commonly encountered in patients with shock, extensive burn, sepsis or severe trauma (Curlingâ&#x20AC;&#x2122;s ulcer), in any intracranial conditions that raises intracranial pressure. Erosion: Is defined as mere shedding of the superficial epithelium of the stomach and occasionally of the duodenum. When they involve the entire mucosal thickness they are termed stress ulcer.

Criteria of erosion: 1) Acute gastric ulcer is usually less than 1 cm is diameter, is circular and rarely penetrates beyond the mucosa. 2) The ulcer base is frequently stained a dark brown by the acid digestion of extruded blood. 3) They may occur singly or more often multiply throughout the stomach and duodenum. 4) Conspicuously absent are scarring or thickening of blood vessels, as seen in chronic peptic ulcer. 5) Healing with complete re-epithelization occurs after the causative factors are removed. Recurrent ulcer: 21 Recurrent ulcerations occur in approximately 5% of all patients after surgery for peptic ulcer. The risk for recurrence is 3 to 10% after surgery for DU and approximately 2% other GU surgery. Recurrence is more common after vagotomy with enterectomy. When ulcers occur after partial gastric resection, the ulcer is usually located at the anastomosis (stomal or marginal ulcer) or immediately distal in the small intestine. Aetiology of recurrent ulcer: 30 Inadequate surgical procedures: Simple gastroenterostomy is the most obvious example of an inadequate surgical procedure in that it fails to reduce vagal stimulation, antral gastritis or parietal cell population. Inadequate vagotomy, inadequate gastric resection, inadequate drainage after gastroenterostomy and pyloroplasty etc. are the common causes of recurrent ulceration.

Unrecognized endocrine factors: Hypergastrinoma is due to Zollinger-Ellison syndrome and antral G-cell hyperplasia. Ulcerogenic agents: Chronic use of aspirin and other NSAIDS have been associated with recurrent ulcers. In Cirrosis of liver when there is congestive gastropathy intake of NSAIDs 3 1 may lead to develop ulcer31. Smoking is also associated with recurrent ulcer32. Tumours of the Stomach:33'34 Benign 1. Hyperplastic polyp

Malignant 1. Carcinoma of stomach

2. Leiomyoma.

2.Metastatic tumour

3. Fibroma.

3. Lymphoma.

4. Neurofibroma

4. Leiomyosarcoma

5. Heterotypic pancreas.

5. Sarcoma.

6. Lipoma.

6. Carcinoid

7. Leiomyoblastoma.

7. Malignant vascular tumor.

8. Gastric cyst.

8. Haemangiopericytoma.

9. Vascular tumours.

9. Haemangioendothelioma 10. Kaposis sarcoma.

Clinically recognizable benign gastric lesions probably occur in about 5% of all patients. 50% of the benign tumours discovered incidentally when investigations done for other reasons. Usually these lesions are symptompless. The most common presentations are pain and gastro-intestinal bleeding. The overlying mucosa of the many submucosal tumours tends to ulcerate and

massive haemorrhage may result. This most often takes the form of melaena, although haematemesis can also occur. 33 Among the malignant tumours that occur in the stomach, carcinoma is the overwhelmingly, the most important and the most common (90 to 95%). Next in order of frequency lymphoma (4%), characinoid (3%) and malignant spindle cell tumour (2%). Esophageal varices: Varies are tortuous dilated veins lying primarily within the submucosa of the distal oesophagus and proximal stomach. Venous channels directly beneath the oesophageal epithelium may also become massively dilated. Oesophageal varices are mainly supplied by the left gastric vein and gastric varices are largely supplied by the short gastric veins and drain into the deep intrinsic veins

of the oesophagus.35 Haemorrhage from the oesophageal varices is a

major complication of portal hypertension. The bleeding from the varices may occur when the portal pressure exceeds 11 to 12 mm of Hg above the

inferior

venacaval pressure. However not all patients with pressure above these levels have bleeding varices. The tension on the vessel wall is greater in larger than in small varices for given pressure. Therefore, large varices are more likely to rupture and bleed than are smaller ones36. Oesophageal varices is a common cause of bleeding and carry a mortality rate of 50% and most survivors rebleed an inpatient mortality of 30%36 and most survivors rebleed an inpatient mortality of 30%11, gastric varices develop in the settings of portal hypertension but ten times less than oesophageal varies. Gastric varices lie within 2 to 3 cm of gastroesophageal junction and rarely occur in the absence of esophageal varices.

Oesophagitis: Injury

the

oesophageal

mucosa with

subsequent

inflammation

called oesophagitis. According to aetiology it is of three types: 1. Reflux 5. Infective 3. Others Reflux oesophagitis: Consists of esophageal mucosal change caused by reflux of gastric or intestinal contents in the oesophagus. Depending on the causative agents it is referred to as peptic, bile or alkaline oesophagitis.38 The normal anti reflux mechanism consists of the lower oesophageal sphincter & the anatomic configuration of gastro-oesophageal junction. Reflux occurs only when the gradient of pressure between the lower oesophageal sphincter (LES) and the stomach is lost. It can be caused by increased intra thoracic pressure or by a transient or sustained decrease in LES tone. Decreased tone may be due to: Primary cause: Due to muscle weakness or to inappropriate sphincter relaxation mediated by inhibitory nerves. Secondary causes: Scleroderma. Myopathy Pregnancy Smoking Smooth muscle relaxant, (Beta-blocker, aminophyline, nitrates and calcium channel blocker) Surgical resection Hiatus hernia. Infective oesophagitis: 39

Most commonly candidal, rarely viral like CMV, HIV and bacterial. Candidal oesophagitis Many Candida species are normal commensal in the throats but become pathogenic and produce oesophagitis

in immunodeficiency states.

Occasionaly monilial esophagi is occurs in absence of any predisposing Factor. Patient may be asymptomatic or complain of odynophagia and dysphasia. Rarely candida oesophagitis is complicated by bleeding, perforation & stricture or by systemic invasion. Mallory-Weiss tear: This is a longitudinal tear below the gastro-oesophageal junction, which is induced by repetitive and strenuous vomiting. Doubtless, many such lesions may occur and does not cause bleeding. When it is a cause of haematemesis the lesion may often be missed as it can be difficult to see as it is just below the gastro-oesophageal junction, a position that can be difficult for inexperienced endoscopes. Occasionally the lesions continue to bleed and require surgical treatment. Tambours of the oesophagus: 40 Benign tumour: 1.

Leiomyoma.

Lipoma.

Angioma

Inflammatory fibroid polyp.

Epithelial papilloma.

Malignant tumour: 1.

Carcinoma of oesophagus.

Sarcoma: sarcoma of the oesophagus is exceedingly rare, but

leiomyosarcoma and rhabdomyosarcoma have been reported. 3.

Malignant melanoma.

CLINICAL CORRELATION : Clinical manifestation depends upon the site, extent and rate of haemorrhage and the presence of coincidental disease. # Blood loss less than 500 ml is rarely associated with systemic signs exception include bleeding in the elderly or in the anaemic patients in whom smaller amount of blood loss may produce haemodynamic alteration. # Rapid haemorrhage of greater volume results in decreased venous return to the heart decreased cardiac output and increased peripheral resistance due to reflex vasoconstriction. # Orthostatic hypotension greater than a change of 10 mm of Hg usually indicates a 20% or a greater reduction in blood volume, concomitant symptoms may include light headedness, syncope, nausea, sweating and thirst. # when blood loss is 20 to 40% of blood volume shock frequently ensues with Pronounced tachycardia and hypotension, pallor and cool skin. # In the settings of rapid haemorrhage, the initial haematocrit may not accurately reflect the magnitude of blood loss, since equilibration with the extra vascular fluid and haemodilution often require over 8 hours. Common laboratory findings include mild leucocytosis and thrombocytosis which develop within 6 hours after the onset of bleeding. BUN may be elevated out of proportion to the creatinine.

Effects of acute haemorrhage: It depends upon two factors: 1.

Amount of blood loss.

Speed with which the loss occurs

If loss of 500 ml: no sign

<20% slight effect.

Sudden loss of 35% or more : Death.

But over 50% of blood volume, not necessarily fatal, if greater than 50% , it is always serious. There is individual variation in the response to blood loss, even though the amount and rate are constant. It is therefore impossible to assess accurately the magnitude of any haemorrhage on purely clinical ground. Some workers like to use the term-massive, moderate and mild in describing the amount of bleeding in cases of haematemesis and melaena. Massive haemorrhage has been described as having the following criteria: 1.

Active haemorrhage.

One or more of the followinga) Shock b) Hb below7gm/dl orHct<25. c) 7 or more units of blood transfusion are required within 24 hours to achieve a stable blood pressure.33

In case of moderate haemorrhage: Blood loss is roughly assumed to be less than 500 ml. Symptoms and signs likegiddiness, weakness, palpitation, sweating, thirst and postural hypotension etc. In mild haemorrhage:

GIT haemorrhage not exceeding 500 ml produces very few symptoms and has been described as mild haemorrhage. Continued or renewed haemorrhage may lead to shock, even though the initial presentation was leveled as mild haemorrhage. This impending catastrophe is detected by the time tested signs: 1.

Increased pulse rate.

Decreasing blood pressure.

Weakening of peripheral pulse.

Increasing pallor, coldness and sweating of skin.

Monitoring of central venous pressure permits the optimal maintenance of blood volume in patients with acute hypovolumia and excellently determines the need for transfusion. The urine output meassured hourly is also an excellent index of tissue perfusion. A drop in urine output 0.5 ml/kg/hour is a good evidence of moderate to marked hypovolumia, provided there is no existing renal disease. Ordinarily the occurence of anuria during shock is associated with poor prognosis. Shock: The

major

consequences

of massive

haemorrhage,

state

insufficient microcirculatory flow, under perfusion and cellular hypoxia. It is clinically characterized by: Rapid thready pulse. Hypotension with systolic BP below 100 mm of Hg. Moist pallor skin. Collapsed veins. Rapid shallow breathing. Anxious, restless, agitated, stupor, coma and death.

Heamatologic and blood volume change: Haematocrit & Hb% level, these are not reliable indicators of the bleeding; for the Haematocrit to fall, the blood plasma must be equilibrated with extracellular or with adminstered intravascular fluids. It takes few hours (3-4hrs) to changes to occur. Massive dilution occurs usually after 24 to 72 hrs, average time is 32 hours. It depends upon: 1. State of body hydration 2. Preexisting anemia. 3. Recurrent or continued bleeding. Therefore, extent of blood loss cannot be ascertained by haemoglobin percentage, haematocrit or erythrocyte count. Even after cessation of bleeding, the Hb%, Hct or erythrocyte count continue to fall till a steady state is attained. White cells: Polymorphonuclear leucocytosis (10,000 to 20,000 / mm 3) occurs in 2 to 5 hours following GI bleeding white cell count becomes normal in 3 to 4 days. There is shift to left in myeloid series. Platelet: Count rises within an hour after a brisk haemorrhage.

Reticulocyte count: Reticulocytosis begins after 24 hrs, and attains peak value (5-15% or more) 4 to 7 days after GI bleeding. Persistence of reticulocytosis after 10-14 days suggests continued bleeding. Change in Hct parallels the changes in haemoglobin. Cardiac changes: MI especially in those with coronary artery disease & elderly, arrhythmia and CCF. Renal and adrenal complication: 1.

Acute tubular necrosis.

Adrenal haemorrhage and insufficiency in case of prolonged shock.

Cerebral effects: 1. Cerebral hypoxia leading to restlessness, anxiety, apathy, sleepiness, confusion, disorientation, delirium and coma. 2. Cerebral vascular thrombosis especially in elderly and atherosclerotic. Hence prompt correction of shock and early ambulation after bleeding is desirable in elderly people. Hepatic effect: 1. Hepatic coma may be precipitated in patient with cirrhosis of liver perhaps due to the effect of shock on liver and absorption of nitrogenous products from gut. 2.

Centrilobular hepatic necrosis.

Change in liver function test.

Effect of recumbence: Hypostatic pneumonia may occur especially in patients with chronic chest disease and also in elderly patients following prolonged recumbency.

DIAGNOSTIC APPROACH Upper GI hemorrhage is a medical as well as surgical emergency which needs immediate resuscitation of the patient, early detection of the cause of bleeding and appropriate treatment. Accurate diagnosis is a prerequisite for improvement in patient care and management. The first priority of any case of upper GI haemorrhage is resuscitation. The second priority is the history, physical examination and investigation. History: It is not always possible to diagnose with certainty the causes of dyspepsia merely from history and examination, either in the routine setting or in the bleeding patient41 However, history from the patient, attendance & family doctor may give some clues to the diagnosis. 1. History of antecedent epigastria pain or discomfort and antacid consumption suggests peptic ulcer disease. 2. Aspirin and other NSAIDs consumption suggest erosive gastritis or gastric erosion. 3. Symptoms and signs of aneamia indicate chronic blood loss, where as anorexia, weight loss and epigastric discomfort and asthenia suggests Carcinoma stomach. 4. Past history of jaundice or ascites suggests variceal bleeding. 5. Dysphagia and discomfort during swallowing suggests benign or malignant oesophageal tumours or oesophagitis, 6. Prolonged forceful retching or vomiting of non bloody materials followed by blood vomiting suggests Mallory-Weiss tear. 7. Presence

of bleeding

disorder,

anticoagulant therapy or

hereditary

telangiactasia suggests the possible cause of bleeding. 8. Presence of fresh clotted blood into the stool for 24 hours after the onset

of bleeding suggests either persistent bleeding or bleeding near to the colon not from upper GIT. 9. Clots in stool indicate massive haemorrhage. If the patient had a haematemesis or fresh melaena in the previous 24 hours, this two is significantly correlated with the mortality which fits with previous studies showing that a major haemorrhage with postural drop in BP, shock or fresh melaena with or without a haemetemesis will be associated with an increase in mortality.42 Physical Examination: 1.

Examination should evaluate the patients general condition and assess the signs of shock and hypovolumia (as for example; pulse. BP respiratory

rate,

temperature,

skin

condition

and

level

consciousness), 2.

Signs of chronic liver disease if present are of crucial importance since patient bleeding from portal hypertension have a high mortality (upto 50%). In the presence of liver failure or ascites, variceal bleeding carries an even higher mortality.

Epigastric tenderness suggests peptic ulceration, oesophagitis, and hiatus hernia.

A palpable epigastria mass with Virchowâ&#x20AC;&#x2122;s node suggests gastric cancer.

Petechiae or ecchymosis suggests a haemorrhagic disorder.

Melanin

spots,

telangiectasia,

neurofibromatosis

and

other

mucocutaneous lesions give clues to the causes of bleeding. 7.

Purpura together with splenomegaly or enlarged lymph nodes suggests blood dyscrasias.45

The presence of aortic valvular disease may be associated with mucosal vascular abnormalities of the intestinal tract.

Investigation: 1. Blood for: I. Grouping and cross matching for patient management. II. Hb% III. ESR - Increased in aplastic anaemia and malignancy. IV. Total count of WBC-Increased after haemorrhage or leucopenia in case of aplastic anaemia V. DC-Neutrophilia after haemorrhage VI. Platelet count- Increased after haemorrhage. VII. BT, CT, VonWF & APTT: When haematological causes are suspected for upper gastrointestinal haemorrhage. 2.

Liver function tests?

When

liver

disease

suspected to be

the

cause

of upper

gastrointestinal haemorrhage, the following tests should be done. I. Serum total protein with albumin and globulin ration. In liver disease serum total protein is reduced with alteration of albumin and globulin ratio. II. Prothrombin time -It is increased in chronic liver disease & in patients on oral anticogulant. III. Serum bilirubin, SGPT is mildly increased in cirrhosis of liver. IV. Viral markers- HBsAg, Anti-HCV, HBeAg. 3. USG of hepatobiliary system in CLD to see hepatic echotexture, splenic size and portal vein diameter. 4.

BUN is helpful indicating previously unrecognize chronic renal failure.

5. Nasogastric aspiration: Is done: I. To determine the site of bleeding. II. To determine whether there is any active bleeding or not. If there is no aspirate through nasogastric tube, it means there is no active bleeding. If the patient shows the features of active bleeding despite negative aspiration indicates that the bleeding is from below the ligament of treitz46. If red blood or coffee ground materials is aspirated from the nasogastric suction, saline aspiration should be instituted. Irrigation serves two puroses: -Assessment of rapidity of bleeding. -Clear the stomach of old clot prior to possible endoscopy. 6. Upper GI endoscopy: Endoscopes have revolutionized the examination of the gastrointestial tract. Because of the flexibility of the instrument & controllability of the instrument tip, the operator can steer the endoscope around multiple bends under visual control. A channel permits the passage of a variety of endoscopic tools, such as biopsy forceps, cytology brushes, wash tube, injecting devices and electro cautery probes and snares. The video endoscope is a modification of the original fibre endoscope in which a charge coupled device on the tip of the instrument transmits the image to a TV screen. This system is being used increasingly because it permits storage, analysis and transmission of the endoscopic images.

Upper Gl bleeding and oesophagogastroduodenoscopy: 47, 48 Endoscopy within first 12 to 24 hours of an upper gastrointestinal haemorrhage is useful in planning rational therapy by visualizing the bleeding source. In formations obtained include1.

Location of the bleeding source.

Whether bleeding is continuing.

Whether bleeding is arterial.

Which of the multiple lesions a bleeding and

Whether a visible vessel is present in an ulcer base.

Recognition of bleeding type: 1.

Visible active bleeding.

Stigmata of recent haemorrhage: a) Presence of adherent clots, which can not be washed off with a powerful jet of water. b) Presence of a visible vessel or an ulcer whose base is hemorrhagic,

Contraindication of upper GIT Endoscopy: Virtually there is no contraindication but relative contraindication are: 1.

Profund shock

Severely compromised cardiopulmonary state

Large zenker diverticula of the pharynx.

Anterior osteophytic proliferation of the cervical spine

Coma

Non cooperative patient

Complications: 1. Perforation 2. Bleeding 3. Transient suppression of respiration due to medication 4. Cardiovascular complication 5. Infection 6. Aspiration. Indication for endoscopy in case haematemesis and melaena: 1. As a first procedure and it is the general recommendation to scope all patients within 24-48 hours of admission following acute episode of bleeding. 2. To locate the exact site of bleeding. 3. When surgery is contemplated. 4. When rebleeding occurs often acute self limited blood loss. 5. When portal hypertension or aortoenteric fistula is suspected. 6. For therapeutic purpose of haematemesis & melaena. a)

In varices-both therapeutic and prophylactic sclerotherapy and

banding. b)

In Focal -non variceal bleeding. Electro coagulation Thermal heat probe technique LASER photo coagulation.

When radiology fails to detect any lesion.

To confirm radiological finding.

When biopsy is indicated.

Endoscopy versus X-Ray: Upper gastro-intestinal radiology using conventional single contrast barium meal is impressingly disappointing as compared with endoscopy in patients with haematemesis and melaena. It is the double contrast barium meal, which is not yet well practiced in Bangladesh, has got superiority regarding accuracy of radiological findings of the GI tract. Endoscopy diagnose over 90% of cases, whereas double contrast radiology diagnose over 80 %49. Moreover a good x-ray machine with television monitoring is much more expensive than an endoscopy. Besides a medical doctor can be trained with a fairly short times for endoscopy 50.

MANAGEMENT Acute upper gastrointestinal bleeding is a medical as well as surgical emergency. The patient should be hospitalized immediately. Steps of management: 1.

Intravenous access: The first step of management is to gain intravenous access using at least one large bore canulla.

Initial clinical assessment of the patient: i.

Assessment of the cardiorespiratory status: Severe bleeding causes tachycardia with hypotension and oliguria. The patient is cold, is sweating and may be agitated.

ii.

To seek evidence of liver disease: Jaundice, cutaneous stigmata, hepatosplenomegaly and ascites may be present in decompensated cirrhosis.

iii.

morbidity:

The

presence

cardiorespiratory,

cerebrovascular or renal disease is important, because these may be worsened by acute bleeding and because these disease increase the hazards of endoscopy and surgical operation.

3. Blood tests: These include: A full blood count. Chronic or subsequent bleeding leads anaemia but the haemoglobin concentration may be normal after sudden major bleeding until haemodilution occurs. 1.

Urea and electrolytes. This may show evidence of renal failure. The urea rises as the absorbed products of luminal blood are metabolized by the liver.

Liver function tests.

Prothrombin time, if there is clinical suggestion of liver disease or in patients.

Cross matching of at least 2 units of blood.

4. Resuscitation: I). Intravenous crystalloid fluid or colloid are given to restore the blood pressure but normal saline should be avoided in patients with liver disease because it can cause ascites. II). Blood transfusion. Indication of blood transfusion is: 1. When the patient is in shock- signs of hemorrhagic shock indicate the urgent need to reestablish an adequate circulation to vital organs. 2. Continuing bleeding, as evidenced by continuing haematemesis or melaena,

persisting

tachycardia,

and

active

bowel

sounds,

also an indication for blood transfusion. 3. A low haemoglobin level: When the haemoglobin concentration is less than 100g/liter. III). Central venous pressure monitoring: It is used in severe bleeding, particularly in patients who have cardiac disease,

to assess in defining the volume of fluid replacement and identification of re bleeding. IV). Oxygen: This must be given by face mask to all shocked patients. V). Monitoring: pulse, blood pressure and urine output hourly. Empirical therapy: For active bleeding: 1. Gastric lavage. 2. Drug therapy. 1. Gastric lavage: It is performed in different centers with the view to remove blood clots, within the stomach and to reduce the rate of blood loss. It has been shown that gastric lavage can cause temporary cessation of bleeding in most of patients, regardless of cause of bleeding. Experimental evidence suggests that room temperature tap water lavage is as effective as ice cold saline lavage. 2. Drug therapy: Approximately 80% of bleeding ceases spontaneously. It has been customary in use some drugs with varying degree of success to control acute episode of bleeding. The drugs are: 1. H2 receptor antagonists e.g. Ranitidine parenteally/orally. 2. H+K+ATPase inhibitor e.g. Omeprazole, lansoprazole etc. H2 recetor antagonists have not shown to be of benefit in stopping bleeding or reducing incidence of rebleeding.70 High dose proton pump inhibitor (i.e. Omeprazole 40 mg or Lansoprazole 60mg have shown to reduce the risk bleeding in patients with peptic ulcer with high risk features (active bleeding , visible vessels or adherent clot). Pending the results of endoscopic examination,

it may be reasonable to initiate therapy with a proton pump inhibitor in patients with suspected peptic ulcer bleeding70. 3. Vasopressin: Can be used intravenously with iv nitroglycerine to lower portal venous pressure to stop variceal bleeding. 4. Somatostatin and octreotide13. These drugs can be used to control oesophageal variceal bleeding. Somatostatin is an effective treatment for the control of non variceal acute UGI bleeding in high risk patients, i.e. those in whom haemorrhage does not cease spontaneously or is likely to recur. In contrast, there is no good evidence available to support a role of octreotide, H2 receptor blocker or proton pump inhibitors in this indication. Pharmacological therapy to prevent recurrent bleeding: For the prevention of recurrent variceal bleeding a non selective betaadrenorecoeptor antagonist like propranolol which lowers portal pressure, can be used and effective now a days. 5 .Endoscopy: Once the patient is haemodynainically stable, endoscopy should be performed to identify the source of bleeding. Early endoscopy also may provide prognostic information to whether the patient is likely to rebleed and to permit ; endoscopic therapy. Depending on the aetiology of the source of bleeding found on endoscopy treatment will vary.

A. Treatment of non variceal group: 1. Peptic ulcer disease: a) Non operative treatment: Some recent non operative advances in the management of upper GI bleeding due to peptic disease are: 1. Thermal endoscopic modalities: a) Laser photocoagulation. b) Endoscopic electro coagulation. c) Heater probe method. 2. Non thermal endoscopic modalities: a) Endoscopic injection sclerotherapy. b)

Spraying.

Spraying

crystalline

collagen,

clotting

factor

cyanoacrylate tissue glue to the bleeding lesion. 3. Angiographic technique. Surgical treatment: I) Emergency surgery. II) Elective surgery. Indication of emergency surgery: When homeostasis fails to stop active bleeding. Rebleeding occurs in one occasion in an elderly or frail patient. Rebleeding occurs twice in young fitter patient.

Indication of elective surgery: 1. When a patient has bled from a gastric or duodenal ulcer on more than one occasion. 2. Visible vessel in the base of the ulcer. 3. Bleeding with evidence of gastrinoma (e.g. Zollinger-Ellison syndrome).

1. Acute erosive gastritis: Gastric erosion are usually are associated with ingestion of gastric irritants, e.g. aspirin and other NSAIDs and alcohol. The lesion usually rapidly regresses with avoidance of the precipitant and use of H2 receptor blocker and proton pump inhibitor. They are also effective in erosive gastritis associated with liver failure. Perfusion of the stomach with ice is sometimes effective in stopping bleeding. Occasionally surgery is necessary when haemorrhage continues. 2. Mallory- Weiss tear: Bleeding usually ceases spontaneously but it may require cautery or injection therapy if bleeding persists. 3. Oesophageal candidiasis: Specific antifungal therapy and removal of the precipitating causes along with the general measure to stop bleeding. Nystatin oral suspension, ketoconazole, fluconazole are effective treatment. The treatment is for 7 to 10 days. 4. Oesophagitis (Non specific): General measure for avoidance of reflux like weight reduction, stopping smoking, antireflux drugs and H2 receptor blockers are used in treating the condition. Omeprazole 20mg in the morning is the drug of choice for reflux oesophagitis16. 5. Neoplasm of upper GIT: Upper GI haemorrhage due to neoplasm may require surgical intervention or palliative chemotherapy because they usually continue to bleed. As an alternative to surgery, selective arterial embolzation, electrocoagulation or laser photocoagulation can be done.

B. Treatment of variceal bleeding:

Oesophageal variceal bleeding usually requires endopscopic intervention. The varices may be actively spurting or oozing blood or may show evidence of recent bleeding by "red wale" marks of cherry red spots. Until now, the most common approach to stop bleeding has been sclerotherapy. Besides selerotherapy, there are also other treatment modalities which are described below: Sclerotherapy: Involves injection of varices with sclerosing agents such as ethanoamine, sodium tetradecyl sulphate, or absolute ethanol. Side effect is oesophageal stricture formation. Banding: Oesophageal variceal banding ligation is an increasingly used technique. It has lowered risk of oesophageal stricture formation and it does not have any systemic toxicity. Vasopressin: Systemic use of vasopressin together with intravenous nitroglycerine lowers portal venous pressure and may be used adjunctively to control variceal bleeding. Similarly systemic somatostatin or it's an analogue (octreotide) can also be used. They do not cause peripheral vasoconstriction, only lowers portal venous pressure.

Baloon temponade: If endoscopes or pharmacological methods fail to control, variceal bleeding, then balloon temponade with the Sengstaken or Blakemore or Limon tube may be used to compress the varices directly and thereby can be attempted Transjugular intra hepatic portosystemic shunt (TIPSS): This procedure involves placing an expandable metal stent through the liver to connect the portal vein and hepatic vein. Other emergency procedures are: 1. Percutaneous transhepatic obliteration of varices. 2. Laser coagulation 3. Electrocoagulation or electrocautery. Long term therapeutic management after variceal bleeding: Treatment options are: 1.

Conservative medical management of the causative liver disease.

Repeated injection sclerotherapy.

Insertion of portosystemic shunts.

Transection & devascularisation operation

Long term prophylactic therapy: Beta blocker such as propranool which lowers portal venous pressure, and propranolol and sclerotherapy are equally effective for the long term care of patients with cirrhosis. AIMS AND OBJECTIVE: 1.

To find out the clinical presentation and aetiology of upper GIT

bleeding. 2. To find out the morbidity or mortality of patients with upper GIT bleeding. 3. To find out the investigation which are mostly helpful in aetiologial diagnosis of the disease. 4. To assess the clinical outcome of the disease. 5. To report precautionary measures for prevention of the disease.

MATERIALS AND METHODS: It is a prospective cross sectional study was carried out in different medicine units of tertiary care hospital like Dhaka medical college hospital and Bangabanbhue sheikh mujib medical University, Dhaka, on randomly selected 100 patients admitted with upper GIT bleeding. Form January to June 2009 was included in this study. The cases were evaluated through 1. Proper history taking 2. Thorough clinical examination 3. Endoscope examination : Endoscopic examination was carried out within 48 hours of first presentation of haematemesis and /or melaena 4. Other related investigations 5. Outcome at he end of the hospital staty. For the purpose of analysis, the cases of acute UGI bleeding are divided into six diagonostic group. Drodenal ulcer, gastric ulcer, oesophagal varices, gastric erosion, Miscellaneous group and source unknown (table-1). Patient from both sexes who were admitted to hospital, Patient presented with haematemesis and melaena who are haemodynamically stable after resuscitation included in this study but patient below 12 years of age, very debilated, patient who were not

stabilized within 48 hours of resuscitation, bleeding from different parts of the body without the history of haematemesis or melaena and contraindication to Endoscopy were excluded from the study. A printed proforma show on appendix was made, to record all the information collected from the patient and for subsequent analysis.

Result All the relevant data have been arranged in tables: Table-1 Aetiological pattern of haemetemesis & melaena (n=100) Aetiological pattern Duodenal ulcer Gastric ulcer Oesophageal varices Gastric erosion Miscellaneous i. Gastric cancer ii.

Reflux

No of patients 38 12 22 8 16 8

Number and percents 34 (34%) 12 (12%) 22(22%) 8 (8%) 16 (16%) 8 (8%)

4 (4%)

Oesophagitis iii.

ITP

2 (2%)

iv.

AML

1 (1%)

1 4

1 (1%) 4(4%)

v. Haemophilla Source unknown

The final diagnosis was made after endoscopy (table-1). Grouping was according to aetiology. Out of 100 cases, peptic ulcer disease was the commonest cause (50%).

Table -2

Aetiological relation with age and sex of the Patients (n=100) Aetiology

Mean age in years

Duodenal ulcer Gastric ulcer Gastric erosion Oesophageal varices Miscellaneous Source unknown

35.5 45 38 45.5 48 42

Sex Male 34 10 6 18 12 3

Male: Female Female 4 2 2 4 4 1

8.5:1 5:1 3:1 4.5:1 3:1 3:1

Over all male to female ratio 4.5:1, indoudeual ulcer it is 8.5:1. In these studies the age incidence was lower in DU. which is 35.5 in comparison to other groups. The ratio between DU and GU is 3:1 and ratio of bleeding peptic ulcer in male and female is 7:1

Table-3 Relation with ulcerogenic agents (n=100) Aetiology Duodenal ulcer Gastric ulcer Varices Erosive Gastritis Miscellaneous Source unknown

Smoking % 19 (50%) 6 (50%) 0 (0%) 2 (25%) 6 (37.5%) 1 (25%)

NSAIDs% 6 (15.78%) 3 (25%) 1 (4.54%) 4 (50%) 1 (6.25%) 1 (25%)

Steroid % 0 0 0 0 0 0

Correlation with upper GI haemorrhage with smoking was found 19 (50%), 6 (50%) and 2 (25%) cases of duodenal ulcer, gastric ulcer and erosive gastritis respectively. NASAIDs also were found 6 (15%), 3 (25%) and 4 (50%) cases of duodenal ulcer, gastric ulcer and erosive gastritis respectively. Table-4 Occupational distribution of the patients (n=100)

Occupation

Total

DU no(%)

number

no Erosion

Varices

Miscellan

Source

(%)

No (%)

eous

unknown

6 (30%) 2 (10%) 8 (40%) 2 (10%) 2 (10%)

no(%) 2 (12.5%) 0 4 (25%) 0 2 (12.5%)

no(%) 2 (50%) 0 0 0 0

4 (25%)

2 (50%)

Service Business Cultivator Student Day

22 (22%) 8 (8%) 28 (28%) 8 (8%) 11 (11%)

8 (21%) 6 (16%) 10 (25%) 4 (10%) 8 (21.05%)

2 (17%) 0 4 (33%) 2 (17%) 1 (8.5%)

2 (25%) 0 2 (25%) 0 2 (25%)

labourer Others

21 (21%)

2 (5% )

3 (24%)

2 (25%) 0

Cultivator 28 (28%), service holder 22 (22%) and student 8 (8%) suffered more

from upper GI haemorrhage. Cultivator 10 (25%), service holder 8 (21%) and business man 6 (16%) suffered

more from doudenal ulcer.

Table-5 Economical status of the patients (n=100) Monthly Total income

Erosion Varices Miscellaneous Source

number no(%) no(%) no(%) n=38

n=12

n=8

no(%)

no (%)

unknown

n=22

n=16

no(%) n=4

<5000 50008000 >8000

60 (60%)

6 (75%)

16 (73%)

8 (150%)

2 (50%)

30 (30%)

(61%) 13

(42%) 5

2 (25%)

4 (18%)

4 (25%)

2 (50%)

10 (10%)

(31%) 2 (5%)

(42%) 2

2 (9%)

4 (25%)

(16%)

Lower income group (<5000/- month) experiences the episode of upper GI haemorrhage much more (60%) of the total, 61% of the duodenal ulcer, 42% of the gastric ulcer, 75% of the erosive gastritis, 73% of the variceal bleeder than other income groups. Table-6 Relation with habitat of the patients (n=100) Habitat Total

no=100 no%

Erosion Varices Miscellaneous Source

no%

unknown

n=38 n=12 n=8

n=22

n=16

no% n=4

Urban

38 (38%)

4 (50%)

8 (36%)

8 (50%)

1 (25%)

Rural

62 (62%)

(32%) 26

(30%) 8

4 (50%)

14(64%)

8 (50%)

03 (75%)

(69%)

(70%)

Rural people (62%) suffered increased episode of upper GI haemorrhage.

Table-7 Clinical Presentation of the patients (n=100) Symptoms

Total

Erosion Varices Miscellaneous Source

no%

unknown

n=38 n=12 n=8

n=22

n=16

no% n=4

20 (20%)

2 (25%)

5 (23%)

4 (25%)

1 (25%)

28 (28%)

(16%) 12

(17%) 4

2 (25%)

5 (23%)

4 (25%)

1 (25%)

52 (52%)

(32%) 20

(33%) 6

4 (50%)

12 (54%)

8 (50%)

2 (50%)

(52%)

(50%)

no=100 no% Haematemesis Melaena Haematemesis & Melaena

Haemaemesis, melaena and both haematemesis and melaena were the presenting features of 20%, 28% and 52% of the patients respectively. Among them 8 (16%) patients of DU, 2 (17%) patients of GU & 5 (23%) patients of oesophageal varices presented with haematemesis and 12 (32%) patients of DU 4 (33%) patients of GU & 5 (23%) patients of oesophageal varices presented with melaena 20 (52%) patients of DU presented with haematemesis and melaena. Table-8 Correlation with past history of the patients (n-100) Past history

Epigastric

Total

D.U

G.U.

Erosion Varics

Misc.

Un-

100

Known

pain (47%) Haemetemesis 24

(64%) 8

(75%) 3

(25%) 2

& melaena Jaundice

(21%) 0

(25%) 0

(24%) 10 (10%)

4 (1%) 8

04 1

(50%) 4

(25%) 2

(27%) 9

(25%) 0

(50%) 1

(41%)

(25%)

Past history of epigastria pain was noted 24 (64%) and 8 (75%) cases of duodenal ulcer and gastric ulcer patients respectively. Past history of jaundice was obtained in 8 (21%) cases with oesophageal varices. Past history of haematemesis and melaena was obtained in 3 (25%) & 6 (27%) cases of duodenal ulcer and oesophagcal varices. Table-09 Correlation with personal history (n=100) Aetiology

H/O-

Sexual Alcohol

1/V drug abuse

Duodenal ulcer Gastric ulcer Oesophageal

exposure 0 0 3

consumption 4 2 2

0 0 2

varices Erosive gastritis

Here duodenal ulcer is associate with alcohol consumption and oesophageal varices with history of exposure and alcohol consumption. Table-10 Analysis of Vital Signs (N=100) Vital sign Pulse (beat/ min)

Position Supine

Mean 95.00

Systolic blood pressure

Sitting Supine

103.00 95.00

Diastolic blood pressure

Sitting Supine

80.00 65.00

Sitting

60.00

Analysis of vital signs show lower normal limit of pulse & BP in supine

position but in sitting position pulse rate rise and blood pressure falls due to postural drop. Table-11 Correlation with sign of the Patients (n=100) Signs Anaemia Epigastric tenderness Splenomegaly Ascites Signs of hepatic failure

Number of Patients 77 65 19 20 18

Percentage 77% 65% 19% 20% 18%

Anemia, epigastric tenderness, splenomegaly were found in 77%, 65% and 19% cases respectively.

Table-12 Haematological and Serological Change of the patients (n=100) Name of the investigation Haemoglobin estimation (g/dl) Total leukocyte count/ mm3 Platelet count/ mm3 ESR mm in first hour HBsAg (Positive) Anti-HCV (Positive)

Mean 6.50 8000 2,90,000 28 14% 2%

Total leukocyte and platelet counts were within normal range. There was mild rise of ESR and moderate fall of haemoglobin values. HBsAg were positive in 14 cases and Anti-HCV was positive in 2 cases. Table-13 Clinical & Endoscopic Correlation of the patients (n=100)

Aetiology Duodenal ulcer Gastric ulcer Erosive gastritis Oesophageal varices Miscellaneous

Clinical diagnosis no% 50 (50%) 6 (6%) 4 (4%) 28 (28%) 7 (7%)

Endoscopic finding no% 38 (38%) 12 (12%) 8 (8%) 22 (22%) 16 (16%)

Clinically 50 cases were diagnosed as duodenal ulcer, 28 cases as oesophageal varices but endoscopically it were 38 and 22 cases respectively.

Table-14 Management of the patients (n=100) Type of therapy H2 blocker Proton pump inhibitor Vasopressin Octreotide Sclerotherapy Banding Surgery

Total 65 90 5 2 10 3 1

Percentage 65% 90% 5% 2% 10% 3% 1%

In managing the cases with haematemesis and malaena 65 patients (65%) were treated with H2 receptor blocker and 90 patients (90%) were treated with proton pump inhibitor (e.g. omeprazole), one patient with duodenal ulcer treated surgically in whom bleeding did not stop in spite of conservative treatment. Among the clinically suspected oesophageal varices patients five were treated with vasopressin and two were treated with octreotide. Among the endoscopically diagnosed a vertical bleeders 10 were treated with sclerotherapy and three were treated with banding.

Table-15

Relation with blood group of the patients (n=100) Blood

Total

D.U. 38

G.U. 12 Erosion Verices

Group A

N=100 30

(30%) 25

(21.05%) (66.7%) (25%) 7 2 2

(30.7%) (25%) 8 4

2 (50%)

(25%) 10

(18.42%) (16.7%) (25%) 3 2 0

(38.3%) (25%) 1 4

(10%)

(7.89%)

(7.7%)

(16.7%)

8 2

22 7

Misc.

Unknown

16 4

4 1 (25%)

(25%)

(35%)

(52.63%)

1 (25%)

(50%)

(23.1%) (25%)

As a whole patient with "O" blood group suffered more (35%) from haematemesis & melaena with especially due to duodenal ulcer (52.63%). Whereas patients- with blood group "A" suffered more (66.7%) from gastric ulcer. Table-16 Requirement of Blood Transfusion of the patients (n=100) Aetiology DU GU Gastric Erosion Oeso Varices Miscellaneous Source unknown

No. of patient

Total

38 12 8 22 16 4

blood 133 36 20 99 40 6

units

of Mean (Unit) 3.5 3.0 2.50 4.50 2.5 1.50

Average needs of blood transfusions were maximum in variceal bleeders followed by those with duodenal ulcer. Table-17 Mean hospital Stay & out come (n=100) Aetiology

No.

Duodenal ulcer Gastric ulcer Gastric Erosion Eso. Varices Miscellaneous Source unknown

patient 38 12 8 22 16 4

of Mean hospital Recovery stay in days 3.5 3.3 5.3 8 4.5 2

36 12 8 20 12 4

Mortality no % 2 (5.5%) 0 0 2 (9%) 1 (6.25%) 0

Maximum hospital stay was in oesophageal varices group (8 days) followed by gastric erosion (5.3 days). Overall moratlity was 5 (5%). Table-18 Recurrence of bleeding during hospital stay (N=100) Aetiology

Number of Treatment Total Conservative Surgery Others patient no (Sclerotherapy, % Banding) 7 (18.42%) 6 1 15 (15%)

Duodenal

ulcer Oeso varices 8 (36.36%) 3 0 5 During hospital stay 15 patients (15% of the total patients), 7 (18.42% from duodenal ulcer and 8 (36.36%) from oesophageal varices group developed recurrent bleeding. Table-19 Characteristic of nasogastric aspiration (n=100) Nasogastric aspiration Positive Negative

Number of patients 70 30

Percentage 70% 30%

Nasogastric aspiration shows 70% of the patients having fresh or coffee ground colour of aspirated material which is suggestive for haematemesis. DISCUSSION In this study, the mean age of the patients was 35.5 years for duodenal ulcer and 45 years for gastric ulcers (Table-2). Mamun 45 in his study showed that the mean age of the patients with upper gastrointestinal

haemorrhage was 35.65 years and 49.40 years for duodenal ulcer and gastric ulcer respectively. Alam46 in his study showed the mean age incidence for duodenal ulcer & gastric ulcer was 36.14 years and 41.6 years respectively. Islam47 found that the maen age incidence of duodenal ulcer was 38.4 years and gastric ulcer 47.0 years. Miah48 in his study found mean age for DU as 42.85 years and that for GU as 41.75 years. Alam49 in his study found mean age for DU as 34.95 years that for G.U as 46years.Our findings in the current study were very similar to the above studies. In the current study male female ratio is 7 for bleeding peptic ulcer. This ratio was 8.5 & 5 for duodenal ulcer and gastric ulcer respectively (Table2). These findings are similar to those of Mamun45.Alam46 and Miah48 found male to female ratio of haematemesis and melaena 6.6, 7.5 and 7.3 respectively. These

findings

are dissimilar

(2.0)

to that

obtained from USA 50.

Zimmerman5Iet.al. also found male preponderance among the bleeders. This increased incidence of the ratio in our country reflects that males are more sufferers. The ratio of bleeding duodenal ulcer to gastric ulcer was 3.5 (Table-2) in the present study. Alam46 Mamun45 and Miah48 found the ratio 5.7, 11.66 and 3.5 respectively. Ratio of bleeding between DU to GU in the western countries varies from 0.8 to 1.2 only. The reason for the higher proportion of the duodenal ulcer to gastric ulcer bleeding in our country than that of the western countries may be due to geographical and racial variation as well as poor heath care facilities.52 ' . Peptic ulcer is the commonest cause of haematemesis and melaena 53. The majority of such ulcers are found in the duodenum. Peptic ulcer disease is responsible for approximately half of all hospital admission with upper gastrointestinal haemorrhage in the western countries. In the present study

peptic ulcer disease is the commonest cause of haematemesis & melaena and comprises 50% and duodenal ulcer is of all cases and gastric ulcer is 38% of all cases and gastric ulcer is 12%. Saowaros at all in a study of endoscopic review of 5000 patients with upper GI haemorrhage in Thailand it was found 51.24% of causes were due to peptic ulcer disease. Zimmermair 51 at all in Jerusalem in a study found 39.5% duodenal ulcer and 16.9% gastric ulcer. Oberale ET al 56 in study found 62.55% of bleeding episode was due to peptic ulcer disease and duodenal ulcer as 53.12%. Alam46 conducted a study in Chittagong medical college hospital and found 75% of haemetemis and melaena were due to peptic ulcer disease and duodenal ulcer was 58.33%. Mamun45 (1992) in a study in Dhaka medical college hospital showed, 56% of the causes of upper GI haemorrhage was due to peptic ulcer disease and duodenal ulcer was 46%. Miah48 in another showed in DMCH in 1995 showed peptic ulcer disease (34%) was responsible for haematemesis and melaena and duodenal ulcer was 26%. Alam 49 in his study showed PUD responsible for 50% for haematemesis & 58% was the leading causes of upper GI haemorrhage which is similar to the study of Mamun 45 and Alam46 but dissimilar to that of Miah48. Variceal bleeding is an important cause of upper GI haemorrhage.In our present study 22% cases (Table-1) were due to variceal bleeding. It was similar to the findings of Alam46, Mamun45 Miah48. Saowaros, 7 in Thailand and Zimmennun in Jerusalem; but dissimilar to those reported from 3% in north Scotland and 2.4% in Oxford55. In USA it is similar to our study (20%).53 The variation in variceal bleeding in different countries could not be predicted properly. In our country consequence of variceal haemorrhage with post viral cirrhosis play a role, as alcoholism in western countries. 57, 58 Erosive gastritis is an important cause of upper GI haemorrhage. It is implicated

in up to 20% of cases of acute upper GI bleeding with an over all mortality of 10%. Mamun45, in his study, found 16% cases of upper GI hemorrhage was due to gastric erosion which was similar to those of Alam

& Zimmerman et al 51;

whereas Miah 48 in his study found only 10%. In our present study, it is only 8% which is similar to that of Miah 48 and Alam49 but dissimilar to those of Mamun 45 and Alam46. This may be due to small number of study population in this study. If the study would done in a large scale this picture could have been changed. Again may be due to intake, of newer NSAIDs and are less irritant to the gastric mucosa and increase consciousness need among both urban and ruler people about adverse effect of NSAIDs. Tomopoulos K et al35 in Greece in a study (1998) of 1534 cases of upper Gl haemorrhage tried to show that the incidence of gastroduodenitis is decreasing than the previous decades. Bleeding source can not be found always inspite of extensive gastrointestinal endoscopy56. The source of bleeding could not be detected at endoscopy in 3 (6%) cases. Mamun45 Miah48 and Alam49 were unable to detect the source of bleeding in: 3(4%) 4(8%) and 3(6%) cases respectively. In the miscellaneous group of this study GIT malignancy contributes 8 (8%) Cases of haematemesis and melaena which is similar to the study of Miah 48 and Alam49. In this group we had 4 (4%) case of oesophagitis, 2(2%) cases of ITP, 1(1%) case of AML & which is similar to that of Miah48 & Alam49. Smoking was associated with 27.7% cases of patient with duodenal ulcer bleeding & 66% cases of gastric ulcer and 25% cases with erosive gastritis. Alam, Mamun and Miah found 40%, 45.83% and 76% cases with duodenal ulcer respectively and 66.6%, 40% and 80% cases with gastric ulcer respectively. Our findings were similar to those of Alam and Mamun. Islam,

found 50% and 50% of patients associated with smoking for DU and GU respectively. Intake of ulcerogenic drugs especially aspirin and other NSAIDs assumed to cause peptic ulceration in 15-25% of patients

and were associated with

relative risk for ulcer bleeding of up to 5 fold. Chalmers et.a'l, 59 in their met analysis recorded that the incidence of upper Gl bleeding was three times more common in patients taking NSAIDs, than in the control group. Up to 22% of bleeding episodes may be due to these drugs with a mortality of 10% 26. In the present series 50% of patients with erosive gastritis. gastric ulcer &

33.3% of patients with

11% patients with duodenal ulcer give history of taking

NSAIDs before starting haematemesis and melaena. Mamun 45 in his study found 20% gastric ulcer and 17.39% patients of duodenal ulcer had history of taking NSAIDs prior to haemetemesis and melaenin. Miah in his study showed 25% of gastric ulcer and 75% of cases of erosive gastritis with upper GI haemorrhage had history of taking NSAIDs. Alam46 in his study has shown that upper GI bleeding due to erosive gastritis occured after exposure to aspirin and other NSAIDs were 60% of the patients. These findings are similar to our finding regarding with erosive gastritis. In our series we found no history of taking steroid in patients with upper GI haemorrhage. There is an increased incidence of duodenal ulcer in stressful occupation. In the present series, 10 (25%), 8 (21%) and 6 (16%) patients with duodenal ulcer with upper GI bleeding were cultivators, service holders and businessmen respectively. Mamun45 in his series found 21.74%, 30.43% & 26.09% of duodenal ulcer bleeders were service holders, businessman and students respectively. Miah48 in his study found 30.7% day labourer, 23% service holders and 15.3% businessmen were duodenal ulcer bleeders. Our findings are similar to those of Mamun, Miah and Alam. Now dayâ&#x20AC;&#x2122;s farmers remain under stressful condition due to their poor socioeconomic condition. They are irregular in

taking meals. Again, as they are very poor, they can not take anti ulcer drugs regularly. The incidence of upper Gl hemorrhage was high 60% of the total bleeders in the lower income group (5000 taka/month). It was 61% in duodenal ulcer group, 48% of gastric ulcer group, 75% of erosive gastritis group, 73% of variceal bleeder group. 30% of the total bleeders were of medium income group (600010000 taka / month) and 10% patients were of higher income group (Table-5) The lower class people suffered more than other class. Tovey28 showed that duodenal ulcer is predominant in lower income group. In these study group rural people 62% suffered more from bleeding peptic ulcer which is similar to Alam75 which was about 58%. In respect of ABO blood group system, "O" preponderance was seen in most (35%) of the bleeders. Patients with upper GI bleeding and among duodenal ulcer patients it was 52.6%. This findings is similar to those of Mamun 45, Alam46 Miah48 and Alam49 who found 39.1% 57.1% 61.5% and 60% respectively of patients with DU bleeders had blood group "O". Most of the patients of the present series had past history of epigastric pain or discomfort which is similar to other studies carried out in Dhaka, Rajshahi and Chittagong .45'46'48'49 In the present series, past history of haematemesis and melaena (Table-9) was obtained in 8 (21%) patients of uuodenal ulcer, 6(37%) patients of variceal bleeding and 2(50%) patients with Ca-stomach. Miah

in his study found

15.3% of DU, 25% of gastric ulcer and 37.0% of oesophageal varices group had history of haematemesis and melaena. Alam49 in his study found 15% of DU

and 37.5% of variceal bleeding our findings regarding duodenal ulcer and variceal bleeders are similar to that Miah48 and Alam49. In the present series, most of the patients with upper gastrointestinal haemorrhage presented with both haematemesis and melaena in 52% cases, melaena in 28% cases and haematemesis in only 20% cases (Table-8). A bleeding duodenal ulcer is likely to be presented with melaena more frequently than haematemesis while a bleeding gastric ulcer patient may present with haematemesis more frequently than melaena. In the present series, patients presented with both haematemesis and melaena in 52%

melaena in 28%

haemetemesis in 20%. In the D.U. group, 52% of patients presented with both haematemesis and melaena and 16.6% presented with haematemesis and 32% presented with melaena each. In variceal group, 54% of patients presented with both heamatemesis and melaena & 23% patients with melaena and 23% patients with heamatemesis. Miah48 showed DU patients presented with both haematemesis and melaena in 46.3% cases, melaena in 38.4%, and haematemesis in 15% cases. Alam46 showed that DU patients presented with haematemesis in 17.1 % cases, melaena in 31.4% cases and both haemeaemesis and melaena in 51.1% cases. Bleeding gastric ulcer & oesophageal varices presented equally 33.3% with both haematemesis and melaena. Variation in presentation in cases of upper GI haemorrhage different studies maybe explained by the fact that haemetemesis and melaena is dependent upon the rate, amount and site of bleeding,

Shock or postural changes in vital signs are the most useful indicator of severity of bleeding. Shock is an indicator of acute blood volume loss of at least 20-40%. In our current study, the mean pulse rate was 95 beats/min and 103 beats/min in supine and sitting position respectively. Mean systolic BP

was 95of Hg and 80mm of Hg in supine and sitting position respectively. The variation in pulse rate & BP was not much significant. This variation depends on the cardiac function, vascular integrity, and state of hydration & intactness of autonomic nervous system of individual patients. Anaemia is reliable guide for chronic blood loss and was found in 77% of cases. Some patients of these series may have some degree of preexisting anaemia due to other causes. Some degree of anaemia can not be explained by the acute loss. Epigastric tenderness was present in 65% of patients of this series; it is a significant physical finding in active peptic ulcer disease. Miah 48 found epigastric tenderness in 70% of cases. Alam46 found epigastric tenderness in 76.6% of cases. Our finding is similar to that of Miah and Alam. Splenomegaly was present in all cases (19%) of variceal bleeding. Stigmata of chronic liver disease with splenomegaly helps in diagnosing a case of cirrhosis clinically. Splenomegaly is the most consistent finding of the patients presented with variceal bleeding. Splenomegaly is also a feature of haematological malignancy. Nasogastric aspirate (Table-16) for blood was positive in 70% of cases of upper GI haemorrhage which is similar to the findings of other studies

46 48

' . Haemoglobin

percentage does not change immediately after haematemesis and melaena. It usually takes 48 hours for haemodilution to occur. In our series the mean Hb% was

6.50gm/dl. HBsAg was done in all cases and Anti-HCV was done in all variceal bleeding patients. HBsAg was positive in 14 variceal bleeding patients. Anti-HCV was positive in 2 cases.

Oesophagogastroduodenoscopy (OGD) is the diagnostic tool in acute upper gastrointstinal haemorrhage60. Duodenal ulcer was diagnosed clinically in 50 (50%) patients but at endoscopy it was only 38 (38%). Accuracy rate was 76%. Azad Khan ET. Al 61 also found accurate diagnosis in 69.65% of the cases. 13of 16 cases. Of clinically suspected variceal bleeding were proved to be correct endoscopically. Alam

also found accurate diagnosis in 83.3% in bleeding peptic

ulcer & 72.72% in case of suspected variceal bleeding. Various literature .showed that in 20-31% of patients bleeding frequently arises from sources other than varices e.g from small erosion in the stomach (portal gastropathy).

62, 63, 64

Recurrent bleeding during hospital stay was found in 15 (15%) cases, 3 cases variceal bleeding 8 (36.36%) and 7 (18.42%) cases of duodenal ulcer bleeders. Kaniz

in a retrospective study of 126 to 1996 in Holy Family Red Crescent

Hospital, Dhaka, found recurrent bleeding in 19.04% cases. Our findings has similarity with that of Kaniz65. Study in UK is also has similarity to our study66. Haematemesis and melaena result from various pathological conditions such as

peptic ulcer, erosive gastrodudenitis, oesophagitis, oesophgeal varices, castomach ca-oesophgus & blood dscrasias. A single therapeutic modality should not consistently reduce bleeding from such an array on selected subgroup of patients such as portal hypertensive naturopathy. Drug treatment may significantly reduce mortality and morbidity. In our present series we used H2 receptor antagonist routinely ihn all variceal bleeding 22 patients although there is no controlled evidence of benefit of use of H2 receptor antagonist or antacid in variceal bleeding though they are used to prevent bleeding from stress induced acute mucosal ulcer. Vasopressin stops variceal bleeding in 35-60% cases65. It controls haemorrhage from oesophageal varices by lowering portal venous pressure. We use vasopressin to 5 & octreotide to 2 of our patients 10 of 22 patients & 3 of 22 patients with variceal bleeding were treated by endoscopic sclerotherapy & banding respectively after stabilizing haemodynamically. The H2 receptor antagonist drugs block the production of acid by the parietal

cells and heal 60-90% of duodenal ulcer over 4to 8 weeks with compared with 35-45% with placebo plus antacid as required for relief of pain 67 In the present series, among 50 patients of haemetemesis and melaena due to peptic ulcer oral H2 receptor blocker in 20(40%) and proton pump inhibitor (omeprazole) in 45(90%) cases. One of our patient with bleeding duodernal ulcer required surgical treatment. Patients with haematemesis and melaena need blood transfusion for resuscitation. Patients need blood transfusion until their vital signs are stable, bleeding ceases and enough red cells in circulation to provide adequate oxygenation54 .In the present study highest blood transfusion was needed in the variceal group(4.50 unit) followed by duodenal ulcer (3.5 unit). This finding is similar to theta of Miah48, Alam46 and Johanston33. In the present series, mean hospital stay was highest in the variceal bleeders (8 days) and it was lowest in the source unknown group (2 days). The mortality of patients admitted to hospital following a diagnosis of acute upper GI bleeding is about 102. Mortality from first bleed from oesophageal varices is around 50% & most survivors rebleed with patient mortality of 30%11 Secondary bleeders have got higher mortality. In our present series 5(5%) patients died during hospital stay; two of them were from DU diseases, two from oesophagal varices & one from miscellaneous group. Miah48 found that the mortality was only 6%. The high rate of mortality from variceal bleeding may be due is the advanced stage of cirrhosis of liver and development of complications such as hepatic encephalopathy, renal failure, rebleeding and hepatocellular carcinoma etc. The mortality from DU diseases is due to having co-morbid conditions. It might also be that most of the patients admitted to hospital were from average and por socioeconomic group who were unable to bear the cost of medicine & blood

transfusion. SUMMARY Fifty cases with episode of upper gastrointestinal haemorrhage admitted into different medical units of Dhaka Medical College Hospital & BSMMU, from January 2009 to June 2009, were studied. Duodenal ulcer was the commonest cause of haematemesis and melaena followed by oesophageal varices, gastric ulcer, erosive gastritis and reflux oesophagitis. The peak incidence was among 35 to 45 years of age. Males were more sufferer than female. Overall male to female ratio were 4.5:1 but in duodenal ulcer it was 8.5:1 Cultivators were the commonest (28%) sufferer of upper GI haemorrhage and amongst duodenal ulcer bleeders service holder (21%) and day labourer (21.05%) followed and businessmen (16.7%). Lower income group patients suffered more than other income group patients. Rural (62%) people suffered more episode of upper GI haemorrhage than urban (38%) people. "O" blood group was commoner among the total cases of haematemesis and melaena and it was also commoner among the duodenal ulcer bleeders. Past history of epigastric pain was noted in 64%, 75% and 25% of duodenal ulcer, gastric ulcer and erosive gastritis respectively. Previous history of jaundice was noted in 10% cases of total patient and among variceal bleeders it was 41%. Haematemesis, melaena and both haematemesis & melaena were noted in 20% 28% and 52% of the patients respectively. Anaemia, epigastric tenderness splenomegaly and ascites were found in 77%, 65%, 19% & 20% cases respectively. Total leukocyte count and platelet count were within normal range. There was moderate fall of hemoglobin values and mild rise of erythrocyte sedimentation rate. Clinically the number of duodenal ulcer, gastric ulcer and erosive gastritis and

variceal bleeders were 50,6, 4 and 28 but at endoscopy it was 38,12,8 and 22 respectively. During hospital stay 7 cases of DU and 8 cases of oesophageal varices suffered from recurrent bleeding. Maximum blood transfusion was needed in variceal bleeder and maximal hospital stay was also noted in the variceal bleeders. CONCLUSION

Haematemesis and melaena is a common medical emergency which needs immediate medical attention. Often it is very difficult to identify the underlying causes of haematemesis and melaena. . Our study, done in a tertiary hospital of Bangladesh, revealed results comparable with studies done in other parts of this country. Peptic ulcer is the commonest cause of upper GI haemorrhage and the majority of the ulcers are located in the duodenum. Other common causes of haematemesis and melaena are ruptured oesophageal varices and erosive gastritis. Sex and blood group distribution are almost similar with other studies conducted at home and abroad. But age distribution varies from country to country and it is a little bit lower in countries like us than those of western countries. Endoscopic examination is the most important diagnostic tool in the diagnosis as well as management of upper GI haemorrhage. Death due to haematemesis and melaena is still a challenge for the investigators

to modify treatment modalities to improve the prognosis. A large scale study is needed to reveal the actual situation regarding aetiology, prompt management to reach a favorable outcome in our country. THREE CASE RECORDS Case-1

Mr. Amanullah 35 years unemployed, non smoker from average socioeconomic income group family, hailing from Kalihati under Tangail district, was admitted into Medicine unit of Dhaka Medical College Hospital on 13.06.2009 with the complains of vomiting of blood for two times, passage of black tarry stool two times and epigastric pain since morning of that day. He had a history of melaena one year back and he has been suffering from occasional epigastric pain for the last 2 years. For this complain he was taking cap-omeprazole (20mg) irregularly. On examination, he had an average body built and nutrition, moderately anaemic but there was no jaundice, clubbing, koilonychia, oedema, dehydration, and lymph nodes were not palpable, hair distribution and skin conditions were normal. His pulse was 110 beats/min, BP-80/50 mm of Hg and respiratory rate was 19/min. abdominal examination revealed tender duodenal point and other systems were normal. After admission a sample of blood was sent for grouping and cross matching, 4 units of blood was transfused. Endoscopy (done on the 2nd day) of upper GIT revealed a round shaped ulcer with active bleeding from its margin situated in the posterior wall of the duodenal bulb. Hb% was 4.8gm/dl, total count of WBC was 8000/cmm, platelet count was 280000/cmm, ESR-25 mm in 1 st hour, liver function tests, BT and CT were normal.

He was treated with Inj. omeprazole. (40mg) intravenously daily with all other supportive measures. On the third -day he again developed an episode of Haematemesis and melaena. He was again transfused with 3 units of blood. Inspite of all conservative management his condition was not improving evidenced by tachycardia, hypotension etc. On the 5th day he was transferred to the surgical ward for proper management. Discussion: Peptic ulcer disease is the commonest cause of upper gastrointestinal haemorrhage. Majority of such ulcers are found in the duodenum53.

Bangladesh duodenal ulcer is also the leading cause of haematemesis and melaena. Duodenal ulcer bleeding is more common than gastric ulcer & morein male than female21, Johnston et al33 in their study found past history of duodenal ulcer in 36% cases, they also found 40% of cases had no abdominal pain or discomfort immediately preceding bleeding and 32% patients had only melaena. Most of the patients respond with conservative treatment. Our patient was suffering from epigastric pain for last 2 years. He had a history of melaena 1 year back. He was on PPI irregularly. He developed same episodes of bleeding while he was admitted in medicine ward and ultimately he was transferred to surgery ward for further management.

Case-2 Mrs. Rahima Banu 50 years, Housewife from an average socioeconomic status came Narinda Dhaka was admitted in a medical unit of DMCH on 30.05.2009 with the complains of vomiting of blood & passage of black tarry stool several times for last one days.

On examination, she was pale looking, moderately anaemic but there was no jaundice, cyanosis, clubbing, koilonychia, edema and lymphadenopathy. She had leukonychia, spider naevi on the front and back of the upper chest, no engorged veins over the abdomen. Her breast atrophied & palms were erythematous. Abdominal examination revealed mild splenomegaly and ascites. Other systemic examination revealed no abnormality. Her Hb was 7 gm/dl, TC of WBC was 8500/cmm, Platelet count 260,000/cmm , ESR-30mm in 1st hour, Serum bilirubin 1.8 mg/dl, serum total protein 6.5 gm/dl, Serum albumin was 3.25gm/dl & s. globulin was 3.25 gm/dl and albumin & globulin ratio 1, Prothrombin time was 17 sec (control 11 sec). HBsAg and Anti-HCV were negative, USG revealed splenomegaly with mild ascites coarser hepatic echotexture. Endoscopy of upper GIT revealed oesophageal varices (grade-2) she was diagnosed as a case of haemetemesis and melaena due to ruptured oesophageal varices. She was managed conservatively with bed rest, blood transfusion 6 units. Intravenous omeprazole, tab, propranolol, bleeding ceased with all of the above measures. Endoscopic sclerotherapy was done two days later. She was discharged after one week with cap-omeprazole, tab spironolactone and propranolol. She was advised to attend the hospital at regular interval for follow up. Discussion: Hepatic cirrhosis is the commonest cause of portal hypertension of all cases with cirrhosis died of upper Gl haemorrhage.

Variceal haemorrhage

occurs in around 30% of patients with chronic liver disease. Mortality from a first bleed is around 50% and most survivors rebreed with an inpatient mortality of 30% Bardirgor Sclerotherapy remains the mainstay of treatment. It controls

bleeding in tipto 90% & can be repeated for rebreeding and adverse effects including oesophageal ulceration and stricture formation are common. Active bleeding during endoscopy makes this process difficult. Vasopressin is a non selective vasoconstrictor that reduces portal venous pressure but achieves control of vertical bleeding in only 50% cases. More recently infusion of somatostatin or its synthetic analogue, octreotide has shown to be highly effective in controlling vertical bleeding. These agents provide acute control of vertical bleeding in up to 80% patients and may be comparable in efficacy to oesophageal sclerotherapy. Our patients got benefit with variceal ligation. Case-3 Mr. Habibur Rahman 60 years, non smoker from an average income group family of Raipura, Narshingdi, was admitted into a medicine ward of DMCH on 13.04. 2009 with the complain of passage of black tarry stool for 4 days. He had a history of epigastric pain for several month for which he was taking cap. Omeprazole. He also gave a history of recent loss of weight. On examination he was found cachexic, pale and severely anaemic with a palpable left supraclavicular lymph node. But there was no jaundice, edema, dehydration, and clubbing koilonychias. Skin condition and hair distribution was

normal.

Abdominal

examination

revealed

epigastic

tenderness.

Examination of other system reveals normal findings. His Hb was 40gm%, TC of WBC was 6000/ cmm, platelet count 200,000/cmm, prothrombin time and BT, CT was normal. , Immediately after admission, a sample of blood was sent for grouping and cross matching. A total of 5 units of blood were transfused. Endoscopy of upper GIT was done on the 2nd day and revealed a huge irregularly shaped ulcerated tumour, covered with bloody uneven floor in the anterior and posterior wall of the body of the stomach extending up to the lesser curvature suggestive of

advanced gastric cancer. Four biopsy specimens were taken from different margins of the ulcer and histopathological examination showed adenocarcinoma of stomach. Discussion: Ca-stomach may present with haemetemesis and melaena. It is usually responsible for about 2% case of upper GI haemorrhage It is extremely common in Japan, China and parts of South America less in UK and uncommon in USA. Gastric cancer is more common in men and the incidence rises sharply after 50 years of age. Helicobacter pylorus is associated with chronic atrophic gastritis and gastric cancer. Diet rich in salted, smoked or pickled food and consumption of nitrates and nitrites are associated with cancer risk. Other risk factors are smoking, heavy alcohol intake etc. Of the gastric cancers 50% occur in the antrum, 20% are found in the cardia and 20-30% is situated in the gastric body. Macroscopically it may be classified as polypoid, ulcerating, fungating or diffuse. Gastric cancer again is classified as early gastric cancer when cancer is confined only to the mucosa and submucosa, regardless of lymph node involvement. Advanced gastric cancer. Early gastric cancer is usually asymptomatic but occasionally can present as dyspepsia. Two-thirds of patients with advanced gastric cancer have weight loss and 50% have ulcer like pain. It may also present as anorexia, nausea, early satiety and haematemesis and/or melaena. Dysphagia occurs in rumours of the gastric cardia obstructing the gastroesophageal junction. Anaemia from occult bleeding is also common. In addition to upper GIT endoscopy, CT scan, endoscopic ultrasound, may be required for staging and assessment of resectiblity of the tumour.

REFERENCES 1. Kenneth R. McQuaid.Current Medical Diagnosis & Treatment Edn, Me Graw Hill. Alimentary Tract 2007; 14: 564-567. 2.

Epsiein A, Issel bacher K.J. Gastrointestinal bleeding. Harrison's Principle of Internal Medicine, 17th Edn, MCGraw Hill.2005; Vol 1: Page: 235-237.

Palmer KR, Penman ID. Diseases of the alimentary system and pancreas, Davidson's Principle and Practice of Medicine. 20th Edn, Churchil Livingstone.2006; 22: Page: 860-868

Elashhoff JD, Grossman ML Trends in hospital admissions death rate for peptic ulcer in the United States from 1970 to 1978 Gastroenterogy 19SO;78;page: 280-285.

Khan AKM, Hassan M, Roy PK et al. Peptic ulcer in Bangladesh. Bang Med Res Councill Bull 1987; XIll (l):29-42.

6. Ali 1. Zulfiqar M & Shah MA. Etiology of haemetemesis. A study of 350 cases, Special Pakistan' journal of medical sciences July-Sept 1999; Vol 15: Page: 301-306. 7/ Sao\varos V, Udayachalem S, Wee Sakal B, Upper gastro intesinal bleeding in Thai patients, review of 5,000 upper GIT endoscopy, J-Med-assoc-Thai, 1995 Nov. 77; page: 561-5. 8.

Schiller, K et al. Haemetemesis and melaena with special reference to factors influencing the outcome. Br Med J 1970, 2; page; 7-14.

9. Allan R, Dykes P. A study of the factors influencing mortality rates from G.I haemorrhage, Q J Med I976; chapter: 45, page: 533-550. 10. Bangerjee ST, Chatterjee a & Ghitacharrya S. Clinical and Endoscopic Evaluation of upper GI Bleeding J. Indian Med. Assoc, 1994 Jul; 92(7) 2212. 11. Jenkins SA, Drug therapy for non-Vertical upper gastrointestinal bleeding. Assessment option. Digestion 1999; 60 suppl 3; 39-49 12. Lewis JD, Shin EJ, Metz DC. Characterization of gastrointestinal bleeding

in severely ill hospitalized patients. Crit Care Med 2000 Jan; 28(l); 261-2. 13.Nijhawan S, Patani T, Agrawal S, Vijayvergiya R, Raj RR. Primary aortoesophageal

fitula

Presenting as massive

upper gastrointestinal

haemorrhage, Indian J Paediatr. 1996 Sept-Oct-63(5); page: 696-8 14. Editorial-Drug treatment of acute upper gastrointestinal bleeding works in selected subgroups of patients, Br. Med. Journal 1992;304,135-136. 15. LAN T Gilmore & Robert Shields-gastro inestinal emergency (1-70). 16.Thomopoulos

K, Katsakoulis E, Vagianos C, Mimklis K, Margariti

V,,NikoIopoulou V. Causes and clinical outcome of acute upper gastrointestinal bleeding , a prospective analysis of 1534 cases, Int J Clin Pract 1998 Nov-Dec; 52 (8); 547-50. 17. Terblance J Issue in gastrointestinal endoscopy, oesophageal varices. Inject, band, medicate or operate, Scand J Gastroenterology. 1992; 63-66. IS.Bogoch A, Berk JE (Ed) Bolkus bleeding peptic ulcer, gastroenterology 4 the edition, vol-l, Phil Adelphia, WB Saunders Company .1985; 65-110. 19. Liberman, D, Gastrointestinal bleeding. Initial management Gastroenterol clin North Am.1993; 80; 1035.

20. Somerville K; Faulkner, G & Langman, M. NSAIDs and bleeding peptic ulcer, Lancet. 1986; 462-4. 2 I. Kenneth R McQueen M.D. Vascular anomalies as a cause of bleeding from upper G.I.T. Current Medical Diagnosis and Treatment. McGrawHill, 2007; 14:564-566. 22. John Del Valle: Peptic ulcer and related disorder, In Harrisonâ&#x20AC;&#x2122;s Principles of Internal Medicine, 2005; Vol 2 page: I746-1747. 23. Crawford JM. The gastrointestinal tract, In Robin's Pathological Basis of Disease, 6th Edn, W.B. Saunders Company .Chapter 18: Page: 775-843. 24. Hudson N, Faulker G, Smith SJ,Late mortality in elderly patients surviving acute peptic ulcer bleeding Gut. 1995; 177-181. 25. Boyd LJS, Wormsley KG. Etiology and pathogenesis of peptic ulcer, In

Berk JE (ed), Bockus Gastro-enterology, 4th ed. vol-l philadephia, WB saunders S Company. 1995; 1013-1059. 26. Graham, Clinical presentation of Acute upper GIT bleeding Br. J. Hosp. 1980; 23:333-337 27. Horrocks J.C. and de Dombal F.T (1978); Gut, 19:19. 28. Tovey FI, Peptic ulcer in India and Bangladesh. 1979; 20:329-347. 29. Silverstein F.E, Gilbert D.A, Tedesco FJ, Buenger N.K. and Persing J. (1981); Gastrointestinal. Endosc, 27, 73. 30. Allison DJ, Hemingway A.P. and Cunninghum D.A (1982); Lancet.33. 31. Jutabha, R, Jensen, D. Management of upper gastrointestinal bleeding in patients with chronic liver disease. Med, Clin. North Am. 1996; 80; 1035. 32. Collin-Jones D.G. Acute upper GI bleeding, Management Topic in gastroenterology 11, 3-12. 33. Johanston SJ, Jones PF, Kyle J, Needhan CD. Epidemiology and course of Gasro-intestinal

haemorrhage

north

east

Scotland,

Br-Med-Jou

1973; 333,655-660. 34.Misra RC, Tevvary A, Jain SK, Dewan R, Menotra SK, Clinico-endoscopic correlation in patient with upper gastro intestinal bleeding; Indian J. Gastroenterology, 1984; 3(4);211-213. 35. NorthfieId TC; Factors predisposing to recurrent haemorrhage after acute gastro intestinal bleeding Br med-j-1971; 1:26. 36. Griffin MR, JM, Daugherly JR, Suowden M, Ray WA, NSAID use and increased risk for peptic ulcer disease in elderly persons Ann-Inter med, 1991;! 14:257-263. 37. McKay DG-Haemorrhagic ulceration of Gut. BMJ July 1971; (p-13) 38. Tanker NC. The diagnosis and management of massive haemetemesis. Br. -Med-J 1965; 51:754. 39. Venegas F, Montalvo RD, Alvarez OA, Donelson SS Lee M. Massive upper gastrointestinal haemorrhage due to cytomegalovirus infection in two

patients with due to cytomegalovirus infection in two patients with acquired immunodeficiency syndrome. South Med J 2000 Feb, 93; (2) 235-8. 40. Askar K, Deeb LS, Biphasic RK, Arnaout MS. Unusual manifestation of an ampullary tumour presenting with severe upper gastrointestinal bleeding. 1999 No-Dec; 60 (6): 583-6 41. Chojkier M et.al. Predictors of outcome in massive upper gastrointestinal haemorrhage, clin Gastroenterol 1986, 8:16-22. 42. Cello J.P and Thoeni R.F (1980) J. Amer. Med Ass.243, 685. 43. Apel D, Riemann JF, Emergency endoscopy, Can J gastroenterol .2000 Mar; 14(3); 199-203. 44. Howand M, Spiro. Clinical gastroenterology .214-339. 45. Mamun, AA. Clinical presentation of upper GIT bleeding, Dissertation 1990. 46. Alam MR. Clinical evaluation of upper gastrointestinal bleeding, Dissertation 1988-81. 47. Islam MN. Clinical picture of endoscopically proven peptic ulcer in Bangladesh. Bangladesh Medical Journal 1982; 10(4)137-142. 48. Miah, Md. Titu. Aetiological pattern of haematemesis and melaena. Dissertation 1996. 49. Alam Towhid. A study on aetiology of upper G.I.T haemorrhage and its prognosis. Dissertation, BCPS. 2000. 50-Culter JA, Mandeloff AL. Upper gastrointestinal bleeding. Nature and magnitude of the problem in US, Dig Dis Sci 1981; 26; 90s-96s. 51. Zimmerman J, Meroz Y, Signencia J, Isvang E. Gastroenterology unit, Hadassah University Jerusalem, Israel. Upper gastrointestinal haemorrhage, Comparison of the causes and prognosis in primary and secondary bleeders, Scand-Jou-gastroenterology; 1994 Sep; 29 (9); 795-8, 52. Hemer B, Kallgard B, Lauritzen G. Haemetemesis and melaena from limited reception area during 5 year period. Acta Med Scand 1965; 177; 483-

492. 53. Wara P. Incidence, diagnosis and natural course of upper GI haemorrhage: Prognostic value of clinical factors and endoscopy, Scand J Gastroenterol 1978; 22(Suppl 137): 26-27. 54. Person WI. Gastrointestinal bleeding. In Sleisenger MH, Fordten JS (Eds), gastrointestinal disease 4th Ed Philadelphia, WB Saunders company. 1989; 397-427. 55. Schiller KFR, Truelove SC, Willums DG. Haemetemesis and melaena, with special reference to factors influencing the outcome. Br J Med 1970; 2:7-14. 56. Oberle E. Burner J, Munch R, Rhyner K, Suspicion of anaemia inducing gastrointestinal bleeding, how far should assessment schweiz. Med. ' wocher-schr. 1992; 122(12); 428-31. 57. Sohrabuzzaman APH. Clinical and histological correlation in the diagnosis of cirrhosis of liver. Dissertation, Dhaka: IPGMR 1987. 58. Hassar, MM. Clinical Presentation of cirrhosis of liver, Dissertation Dhaka, IPGMR 1989.

59. Chalmer TC, Berrier J, Hewitt P ET. all Meta-analysis of randomized controlled trials as a method of estimating rare complications of NSAIDs therapy Aliment Pharmacol Ther 1988;2(suppl)9-26. 60. Chung YF, Wong Wk, Soo KC, Diagnostic failures in endoscopy for acute upper gastrointestinal haemorrhage. Br J Surg 2000 May 87(5); 614-7. 61. Azad Khan AK, Alam MM, Mohsen AQM, Hoque KM. Upper gastrointestinal endoscopy-experiencey in IPGMR. Bang Med J 1982! 1(1): 15-22. 62.Merigin

TC, Hollister RM, Hryska PF, Starkey WB, Davidson CS;

Gastrointestinal bleeding from cirrhosis. A study of 172 episode in 158 patients. N Eng J med 1960; 263:263:579-585. 63. Thomas E, Rosenthal WS, Rymer W, Kats D: Upper gastrointestinal haemorrhage in patients with alcoholic liver diseases and oesophageal

varices: Source outcome and short term impact on liver function. AM J Gastroenterol 1979; 72; 623-629? 64. Dagradi AE, Mehlar R, Tan DTD, Stempein SJ. Sources of upper gastrointestinal bleeding in patients with liver cirrhosis and large esophagogastric varices. Am J Gastroenteroll 1970; 54:458-463? 65. Moula, Kaniz, Mohammad R.J. Experienced with upper gastrointestinal bleeding in relation to endoscopy, Annals official journal of the college of general practitioner of Bangladesh, Aug 2000; Vol-1: page: 12-14 66. Clinical assesment of acute upper gastrointestinal bleeding in selected subgroups of patients, Br. Med. Journal 1997; 304, 135-136. 67. Sherlocks Dj. Portal Venous system and portal hypertensio Lancet-19978, 31: 241