Development of a cost-effective ex vivo lung perfusion system for lung transplantation in India

Background & objectives: Standard donor lung preservation with cold flush and storage allows up to six hours between retrieval of lungs from the donor and transplantation in the recipient. Ex vivo lung perfusion (EVLP) systems mimic physiological ventilation and perfusion in the donor lungs with potential for prolonged lung preservation and donor lung reconditioning. In this study, it was aimed to perform EVLP on discarded donor lungs using a locally developed EVLP system. Methods: Equipment that are routinely used for cardiac surgeries were collected and a functional EVLP system was assembled. This system was used on five pairs of lungs retrieved from brain-dead organ donors. The lungs were ventilated and pulmonary circulation was continuously perfused with a solution containing oxygen and nutrients for four hours. The system was tested without red blood cells (RBCs) added to the solution (acellular group; n=3; A1, A2 and A3) and also with RBCs added to the solution (cellular group; n=2; C1 and C2). Results: The EVLP system was successfully used in four (A1, A2, A3 and C2) of the five lung pairs. Mechanical and gas exchange functions of the lungs were preserved in these lung pairs. One lung pair (C1) worsened and developed pulmonary oedema. Histopathological examination of all five lung pairs was satisfactory at the end of the procedure. Major challenges faced were leakage of solution from the system and obstruction to drainage of RBCs containing solution from the lungs. Interpretation & conclusions: The results of the present study suggest that, it is possible to maintain the lungs retrieved for transplantation in a physiological condition using a locally prepared EVLP system and a solution without RBCs.

Invasive micropapillary carcinoma of urinary bladder: A clinicopathological study.

Context: Micropapillary variant of urothelial carcinoma (MPUC) is a rare but well-recognized tumor of the urinary bladder. Tumors with micropapillary areas accompanying conventional urothelial carcinoma are more aggressive compared to conventional urothelial carcinoma and show variable keratin 7, keratin 20 and human epidermal growth factor receptor 2 (Her 2)neu expression. Aim: The aim of the study was to analyze the clinical, morphological and immunohistochemical profi le of MPUC. Materials and Methods: Transurethral resection of bladder tumor (TURBT) chips of seven cases of invasive MPUC with subsequent cystoprostatectomy specimens of five patients was reviewed. Epithelial membrane antigen (EMA), Keratin 7, Keratin 20, and Her 2 immunohistochemistry were performed in all cases. Follow-up information was available for all patients (2-36 months). Results: All seven patients were male, and their ages ranged from 50 to 62 years. All cases presented with hematuria. The micropapillary pattern was seen in 20-95% of the tumor. All cases showed extensive lymphatic emboli with detrusor muscle invasion. Lymph node metastasis was present in all cases undergoing cystoprostatectomy except one. Keratin 7 and abluminal pattern of EMA positivity were seen in all cases. Keratin 20 was positive in fi ve cases (71%), and Her 2neu positivity was seen in four cases. Three patients died 2, 3, and 6 months after initial diagnosis, among which two were Her 2 positive and one was Her 2 negative. There was no clear prognostic signifi cance of Her 2 positivity. Conclusion: (1) MPUC is a rare but highly aggressive tumor. (2) Micropapillary is usually the predominant pattern. (3) Keratin 7 is expressed universally, whereas Keratin 20 expression is variable. (4) Her 2 expression has no clear infl uence on the survival

Vallecular cyst-revisited.

We report a 3 months-old-male infant presented with recurrent cough, noisy breathing and regurgitation of feeds since 15 days of life. Examination revealed inspiratory stridor. CECT showed cystic lesion in base of tongue. After excision it was proved a case of vallecular cyst on histopathology. Although rare, vallecular cyst should be included in the differential diagnosis of congenital laryngeal stridor in neonates. The literature of vallecular cyst is being reviewed in the current article.

An autopsy report of a rare pediatric lung tumor: pleuropulmonary blastoma.

An autopsy report of pleuropulmonary blastoma (PPB) is described in a two-and-a-half-year-old male child who died within a few days of starting chemotherapy. Autopsy revealed a large tumor almost occupying the whole of left hemithorax with widespread extension to pleura. The diagnosis was confirmed to be PPB, type III on autopsy.

Membranoproliferative glomerulonephritis in a carcinoma with unknown primary: an autopsy study.

Kidney disease frequently complicates malignancy and its treatment. Although many solid and hematologic cancers may involve the renal parenchyma, clinical sequelae are usually not prominent. Published reports cite membranous nephropathy as the most common malignancy-associated glomerulopathy, occurring with many carcinomas and occasionally with leukemia and lymphoma followed by minimal change disease. Rarely membranoproliferative glomerulonephritis (MPGN) has been reported in patients with malignancy. The mechanism by which malignancy induces disease remains unproved, but may involve deposition of tumor antigen in the subepithelial space with in situ immune complex formation and subsequent complement activation. Treatment of the underlying malignancy may lead to resolution of nephrotic syndrome, lending indirect support to this theory. We report a rare autopsy case of a patient with metastatic carcinoma (with unknown primary) associated with MPGN. The association between MPGN and metastatic carcinoma with unknown primary is uncommon and has not been previously reported in the literature.

Insulin tolerance test is comparable to homeostasis model assessment for insulin resistance in patients with nonalcoholic fatty liver disease.

INTRODUCTION: Insulin resistance (IR) is common in patients with nonalcoholic fatty liver disease (NAFLD). We compared the performance of insulin tolerance test and the homeostasis model assessment (HOMA) for measuring IR in such patients. METHODS: In a prospective study, IR was determined using both insulin tolerance test and HOMA in 22 patients with NAFLD. Rate constant for insulin tolerance test (KITT) was calculated using the formula KITT (%/min) = 0.693/t(1/2), where t(1/2) was calculated from the slope of plasma glucose concentration during 3-15 minutes after administration of intravenous insulin. IR was assessed using HOMA as the product of fasting insulin (microU/L) and fasting plasma glucose (mmol/L) levels divided by 22.5. RESULTS: All the 22 patients had IR. Results of KITT and HOMA-IR for determining IR showed a fair correlation (r = 0.55; p = 0.03). CONCLUSIONS: Insulin tolerance test may be a useful method for assessing IR in patients with NAFLD.

Disseminated herpes simplex infection with cystic fibrosis: a case report.

A 6 months old female infant presented with history of fever, cough and severe respiratory distress. There was past history of recurrent attacks of pneumonia. She succumbed to the illness after a hospital stay of 7 days. Postmortem revealed morphological evidence of cystic fibrosis along with herpes simplex infection of liver and adrenals. The co-existence of disseminated herpes simplex infection and cystic fibrosis is very rare.

Histopatholgical spectrum of thymic neoplasms: twelve-year experience at a referral hospital in north India.

This study was undertaken to determine the histopathological spectrum and clinical profile of thymic neoplasms at a tertiary referral care centre. A total of 96 thymectomy specimens were received during the study period (1992-2004), which consisted of 54 neoplasms and 42 benign lesions. Among the neoplasms there were 48 thymic epithelial tumors, 3 thymolipomas and 3 thymic carcinoids. The former comprised of 36 male (75%) and 12 female patients (25%) ranging in age from 2-70 years (mean 37 years). Among paraneoplastic syndromes in thymic epithelial tumours, 27 out of 48 (56.25%) cases were associated with myasthenia gravis and one case was associated with pure red cell aplasia. The most frequent histological subtype was cortical thymoma (43.24%) followed by predominantly cortical (24.32%) and well-differentiated thymic carcinoma (18.92%). On staging, all cases of mixed and predominantly cortical subtype were stage 1 whereas one medullary and 2 cortical thymomas and 4 well differentiated thymic carcinoma (WDTC) showed pleural and pericardial invasion (stage III). This study has revealed that half of thymic epithelial tumours presented as myasthenia gravis. The cortical thymoma was the most frequently encountered histologic subtype and most commonly associated with myasthenia gravis.

Unconjugated hyperbilirubinemia in nonalcoholic steatohepatitis--is it Gilbert's syndrome?

BACKGROUND: Patients with nonalcoholic steatohepatitis (NASH) have normal liver function tests except for raised transaminases until they have progressed to cirrhosis of liver. The objective of this study was to evaluate patients of NASH for the presence of hyperbilirubinemia at presentation. METHOD: Sixty-seven patients of NASH were studied for the presence of hyperbilirubinemia at presentation. All patients were worked up for the presence of cirrhosis and hemolytic work up and fasting test were done in those found with unconjugated hyperbilirubinemia. RESULTS: Five out of 67 patients (7.5%) of NASH were found to have unconjugated hyperbilirubinemia. Though the fasting test was not positive, they all had a negative hemolytic workup and none of them had underlying cirrhosis. Clinical characteristics of patients with unconjugated hyperbilirubinemia were similar to those with normal serum bilirubin levels. CONCLUSION: Unconjugated hyperbilirubinemia in patients with NASH may suggest an associated Gilbert's syndrome.

Pseudomesotheliomatous presentation of primary signet ring cell carcinoma of lung.

Signet ring cell carcinoma is a unique mucin secreting adenocarcinoma. It generally arises from stomach, colon, rectum or breast and rarely from lung. Pleural membrane involvement is common in lung cancer manifesting as pleural effusion. Rarely, it may encase the whole lung without effusion mimicking mesothelioma and is termed as "pseudomesothelioma". A 35-year-old male presented with a pleural mass encasing the whole of the right lung without any pleural effusion and investigations revealed it to be primary signet ring cell adenocarcinoma of the lung.

Acute liver failure and severe hemophagocytosis secondary to parvovirus B19 infection.

Parvovirus infection presenting as severe hemophagocytosis is extremely rare. We report a 13-year-old girl with acute parvovirus infection who had severe hemophagocytosis resulting in severe pancytopenia and hepatic failure.

Inflammatory pseudotumor of gall bladder fossa of liver.

Inflammatory pseudotumor has been described in the lung, liver and other sites, but pseudotumors of the gall bladder fossa have not been reported earlier. We report a 39-year-old woman with inflammatory pseudotumor of the liver in the gall bladder fossa that resembled carcinoma gall bladder.

Transfusion associated graft versus host disease.

Transfusion-associated graft-versus-host disease (TA-GVHD) is a dreaded complication in immunocompromized hosts. The diagnosis is often delayed because of lack of awareness and the non-specific clinical features. More than 90% patients succumb to refractory infections. The only effective preventive measure is administration of irradiated blood products, which must be made available in centers managing immunocompromised patients. We report three cases and discuss pathophysiology and preventive strategies in this communication.

Assessment of insulin resistance and effect of metformin in nonalcoholic steatohepatitis--a preliminary report.

INTRODUCTION: Insulin resistance plays a major role in the pathogenesis of nonalcoholic steatohepatitis (NASH). Insulin-sensitizing drugs like metformin may have a role in the treatment of this disease. OBJECTIVE: To determine insulin resistance and the role of metformin in the treatment of NASH. METHODS: We prospectively studied 25 patients with NASH over a period of one and a half years. In addition to clinicopathological profile, we studied the insulin resistance by insulin tolerance test in 10 of them; seven of them, who did not respond to 3 months of low-calorie, low-fat diet, exercise, weight reduction and ursodeoxycholic acid (UDCA), were treated with metformin for six months. Results were compared with control groups. RESULTS: All 10 patients with NASH tested had low insulin sensitivity; there was significant difference in the rate constant for insulin sensitivity (Kitt) between patients with NASH and normal volunteers. Thirteen (52%) patients responded to dietary restriction, exercise, weight reduction and UDCA. Four of 7 patients treated with metformin had normalization of ALT. CONCLUSION: Patients with NASH have insulin resistance. Metformin may have a role in the treatment of these patients.

Prevalence of obesity, diabetes mellitus and hyperlipidaemia in patients with cryptogenic liver cirrhosis.

Non-alcoholic steatohepatitis (NASH) is emerging as an important cause of cryptogenic cirrhosis. Obesity, diabetes mellitus and hyperlipidaemia are important risk factors for NASH. The presence of these risk factors in patients with cryptogenic cirrhosis may suggest NASH as an aetiology of cirrhosis in them. Twenty-five patients of cryptogenic cirrhosis were compared with 18 patients of hepatitis B virus and hepatitis C virus related cirrhosis and primary biliary cirrhosis for the presence of obesity, diabetes mellitus and hyperlipidaemia. Patients with cryptogenic cirrhosis were found to have a significantly higher body - mass index increased prevalence of diabetes mellitus and lower high-density lipoprotein compared to the controls. Increased body weight and diabetes mellitus may play a role in the causation of cirrhosis in patients with cryptogenic cirrhosis.

Papillary carcinoma thyroid presenting as a choroidal metastasis. Report of a case and brief review of literature.

A patient of papillary thyroid carcinoma, who initially presented with a choroidal metastasis and secondary intractable glaucoma is reported. The orange-coloured tumour posed a diagnostic difficulty, until histopathology of the enucleated eye confirmed the metastasis from the thyroid. The initial presentation of distant metastasis in patients with thyroid cancer is rare.