Recombinant Macrophage Targeted Enzyme Replacement Therapy for Gaucher Disease in India.

Objective: Gaucher disease in India has been reported only in a few case reports from India. The aim of the study was to assess the response to enzyme replacement therapy in Indian patients with Gaucher disease. Design: Retrospective analysis of patients receiving CHO-derived recombinant macrophage-targetted glucocorebrosidase. Setting: Five centers from India with experience in treating lysosomal storage disorders. Patients: The diagnosis of Gaucher disease was confirmed by low glucocerebrosidase levels, though it was first made on splenectomy in 8 and on bone marrow examination in 9 patients. Twenty five of 52 patients diagnosed with Gaucher disease (17 Type I, 8 mild Type III) received treatment for >6 months. Indications for treatment included symptomatic anemia, thrombocytopenia, organomegaly, bone disease or mild neurological symptoms leading to impairment of quality of life. Patients with significant neurological involvement were excluded. The drug infusions were given intravenously every 15 days. Main Outcome measures: Hemoglobin, platelet counts, liver and spleen volumes and growth parameters. Results: 22 of the 25 children who survived were analyzed. After 6 months of treatment, the mean (range) increase in hemoglobin was 1.5 (-3.4 to 6.1) g/dL (P=0.01) and in platelet count was 32 x 109/L (-98.5 x 109 to 145.5 x109) /L (P=0.02). The mean (range) increase in weight was 3 kg (-5.6 to 10.5) (P=0.04) and in height was 7.1 cm (0 to 26.5) (P=0.0003). Liver size decreased by a mean (range) of 38.5% (- 5.5 to 86.7) (P=0.0003) and the spleen size by 34.8% (0 to 91.7) (P=0.004). All patients had improvement in bone pains and in 2 patients, neurological symptoms improved with others remaining static. Conclusions: This is the first reported cohort of patients in India reporting our experience with imiglucerase enzyme replacement therapy for treatment of Gaucher Disease in India.

Transjugular Intrahepatic Portosystemic Shunt (TIPSS) for Budd Chiari Syndrome.

We report a four year old boy who presented with liver failure secondary to antithrombin III deficiency related Budd Chiari syndrome. He was treated with TIPSS (transjugular intrahepatic porto systemic shunt) which reversed the encephalopathy, normalised the liver function and improved growth, pre-empting the need for a liver transplantation. This is the first reported case of TIPSS in a child with a fulminant presentation of Budd-Chiari Syndrome.

Dapsone hypersensitivity syndrome with coexisting acute hepatitis E.

A 14-year-old girl presented with fever, generalized lymphadenopathy, skin rash and hepatitis after starting dapsone. All abnormalities reversed with institution of prednisolone therapy after discontinuation of dapsone. The hepatic involvement was of hepatocellular type; it was associated with IgM anti-HEV antibodies, suggesting coexisting acute hepatitis E. We believe a causal link between the hepatotrophic viruses and dapsone hypersensitivity syndrome could exist.

Hepatic sickling crisis mimicking recurrent cholangitis.

A 22-year-old man with homozygous sickle cell disease presented with recurrent fever, right upper quadrant pain and jaundice. Liver biopsy confirmed the diagnosis of hepatic sickling crisis; the symptoms responded to hydroxyurea therapy. Hepatic vasocclusive crisis can diagnosed on liver biopsy, and need not be a diagnosis of exclusion.

Portal hemodynamics in chronic liver disease.

Portal hypertension is a result of interplay of numerous static and dynamic forces. Portal hemodynamic characterization involves pressure and flow studies which in turn estimate portal pressure. Hepatic venous pressure gradient is the gold standard for determining portal pressure. Portal hemodynamic measurement has helped to understand the pathogenesis and prognosis of chronic liver disease and to define clinically important hepatic venous pressure gradients. Management strategies for ascites and prevention of variceal hemorrhage have been influenced by hemodynamic studies in animals and humans. The hemodynamics in non-cirrhotic portal fibrosis is ambiguous. The role of portal hemodynamic studies outside clinical trials needs further study.

Autoimmune sclerosing cholangitis: an overlap syndrome in a child.

We report an overlap syndrome of autoimmune chronic liver disease and primary sclerosing cholangitis in a young girl. This could be the first such report from India.

Epidemiology of digestive tract cancers in India. II. Stomach, and gastrointestinal lymphomas.

The incidence of stomach cancer and GI lymphomas is low in most parts of India. There is paucity of analytical epidemiologic data on these from India. While the time trends for the incidence of gastric cancer are encouraging, most cancers are diagnosed in an advanced stage when long-term cure is only a remote possibility. Multi-center epidemiologic studies should be undertaken to solve some of the enigmas and observations peculiar to India.

Intrapulmonary vascular dilatations with hypoxemia in extrahepatic portal vein obstruction.

Several mechanisms have been suggested for the development of hypoxemia in cirrhosis. A few patients of portal hypertension due to non cirrhotic liver disease with cyanosis have also been reported earlier. We report probably the first documented case of portal hypertension with portal cavernoma and a normal liver, who had intrapulmonary vascular dilatations leading to hypoxemia and cyanosis. Our case suggests that changes leading to hypoxemia can occur due to portal hypertension alone, in the presence of a normal liver.

Splenic abscess--a possible complication of endoscopic variceal sclerotherapy.

Endoscopic variceal sclerotherapy, though a safe and effective therapy for esophageal varices, is not devoid of local and distant complications. We report a patient with postnecrotic cirrhosis and diabetes mellitus who developed a splenic abscess while on a sclerotherapy program. The abscess may have been a consequence of retrograde thrombosis of the portal venous system or of bacteremia following sclerotherapy.

Pulmonary function tests in cirrhotic and non-cirrhotic portal hypertension.

OBJECTIVE: To determine pulmonary functions in portal hypertension of different etiologies and with various grades of ascites. SETTING: Gastrointestinal clinic in a large community based and secondary referral hospital. PATIENTS AND METHODS: Forty five patients with portal hypertension, including 19 cirrhotics with tense ascites, 8 with moderate ascites, 6 with no ascites and 12 patients with non-cirrhotic portal hypertension. All patients underwent basal pulmonary function testing by spirometry and helium dilution technique, and arterial blood gas estimation and measurement of ascitic fluid pressure. Patients with tense ascites underwent paracentesis of up to 2 liters following which ascitic fluid pressure and pulmonary functions were estimated again. MAIN RESULTS: In cirrhotic patients without ascites, FVC (forced vital capacity), RV (residual volume), TLC (total lung capacity) and FRC (functional residual capacity) were lower than predicted values. In patients with ascites, FVC, FEV1 (forced expired volume in one second) and FEF25-75 (forced expired volume in one second) and FEF25-75 (forced expiratory flow rate between 25% and 75% of forced vital capacity) were significantly lower as compared to predicted values. FVC, FEV1, FEF25-75, pO2, pCO2 and SaO2% decreased significantly with increasing ascites. Paracentesis in patients with tense ascites led to clinical improvement and significantly improved lung volumes. CONCLUSIONS: Pulmonary functions are impaired in patients with cirrhosis, and ascites causes further deterioration. Patients with non-cirrhotic portal hypertension have normal pulmonary functions.

A prospective study of radiation induced damage of pancreatic ducts.

To study radiation-induced pancreatic duct damage, endoscopic retrograde pancreatograms of 11 patients with primary gastric lymphoma who had completed chemotherapy and moderate dose external radiation therapy were compared with those of 22 normal subjects. No significant alteration was seen in the length and caliber of the main pancreatic duct and number of side branches. Clubbing of one or two side branches was observed in four patients who had received radiation (p = ns). We conclude that significant structural changes do not develop in the pancreas following moderate dose upper abdominal radiation.

Radionuclide assessment of peritoneovenous shunt patency.

Denver shunt patency can be easily assessed by sequential scintigraphy with a Gamma camera after an intraperitoneal injection of 99mTc sulphur colloid. If the shunt is patent, the tracer will be seen throughout the shunt upto it's opening into the right atrium. The following case report illustrates the application and usefulness of this procedure.

Out-patient esophageal dilation: an experience in 130 patients using Savary-Gilliard dilators.

Experience of outpatient esophageal dilation using Savary-Gilliard dilators in 130 patients during a 17 month period is reported. The strictures were radiation induced (48), tumoral stenoses (40), anastomotic (16) and due to other causes (26). Both fluoroscopy and endoscopy were used in 58%, endoscopy alone in 23% and fluoroscopy alone in 19% of patients for placement of the guide wire. One hundred and twenty six stricture dilations (97%) were technically successful. Eighty one (62%) patients could be dilated to 14 mm or more. One hundred and nineteen (94%) patients were dilated in one or two sessions. Among the 109 patients who followed up, dilation was successful in providing adequate dysphagia relief in 97 patients and facilitated the performance of other therapies in 9 patients. Major complications included severe continuous chest pain (1 case), hematemesis (2), fever (4) and transient stridor (2). The patient with persistent pain and 9 patients undergoing other therapies required hospitalization. There were no perforations or death. We conclude that esophageal dilation with Savary-Gilliard dilators is safe and effective even in tumors and post-radiation strictures. It can be performed on an outpatient basis in a majority of patients.

Outpatient dilation of anastomotic strictures of the upper gastrointestinal tract.

Anastomotic upper gastrointestinal strictures in 32 patients were dilated on an outpatient basis. Strictures had developed following resection-anastomosis of the esophagus in 27, total esophagectomy in two and total/partial gastrectomy in three patients. Patients with benign anastomotic strictures (group A; n = 21) presented within 6 (median 2) months of surgery while those with recurrent tumors at the site of anastomosis (group B; n = 11) presented 7 (median 14) months later. Dilation using Savary-Gilliard (n = 24), through the scope balloon (n = 2) and Eder Puestow (n = 1) dilators or a combination of these (n = 1) was possible in 20 (95%) patients in group A and 8 (73%) patients in group B. All the 28 patients had relief of dysphagia. Median duration of response after first dilation was 4.2 and 1.2 months in groups A and B respectively. Nature of previous surgery, length of the remaining stomach and recurrence of tumor at anastomosis appeared to affect the technique and outcome of dilation. Savary-Gilliard dilators can be used in a majority of patients except those with short stomachs where through the scope balloon dilators may be preferred.

Double primary neoplasms of the stomach and kidney.

We report a case of synchronous double primary neoplasms of the stomach and kidney. Immunohistochemistry confirmed the two primaries to be of different origin based on antigen expression.

Percutaneous endoscopic gastrostomy for enteral feeding.

Percutaneous endoscopic gastrostomy was performed for enteral feeding in a patient with orocutaneous fistula. The method of construction of the gastrostomy tube from locally available material is described.