Evidence for presence of mismatch repair gene expression positive Lynch syndrome cases in India.

Lynch syndrome (LS), the most common form of familial CRC predisposition that causes tumor onset at a young age, is characterized by the presence of microsatellite instability (MSI) in tumors due to germline inactivation of mismatch repair (MMR) system. Two MMR genes namely MLH1 and MSH2 account for majority of LS cases while MSH6 and PMS2 may account for a minor proportion. In order to identify MMR genes causing LS in India, we analyzed MSI and determined expression status of the four MMR genes in forty eight suspected LS patient colorectal tumor samples. Though a majority exhibited MSI, only 58% exhibited loss of MMR expression, a significantly low proportion compared to reports from other populations. PCR-DNA sequencing and MLPA-based mutation and exonic deletion/duplication screening respectively, revealed genetic lesions in samples with and without MMR gene expression. Interestingly, tumor samples with and without MMR expression exhibited significant differences with respect to histological (mucin content) and molecular (instability exhibited by mononucleotide microsatellites) features. The study has revealed for the first time a significant proportion of LS tumors not exhibiting loss of MMR expression.

Evidence for possible non-canonical pathway(s) driven early-onset colorectal cancer in India.

Two genetic instability pathways viz. chromosomal instability, driven primarily by APC mutation induced deregulated Wnt signaling, and microsatellite instability (MSI) caused by mismatch repair (MMR) inactivation, together account for >90% of late-onset colorectal cancer (CRC). Our understanding of early-onset sporadic CRC is however comparatively limited. In addition, most seminal studies have been performed in the western population and analyses of tumorigenesis pathway(s) causing CRC in developing nations have been rare. We performed a comparative analysis of early and late-onset CRC from India with respect to common genetic aberrations including Wnt, KRAS, and p53 (constituting the classical CRC progression sequence) in addition to MSI. Our results revealed the absence of Wnt and MSI in a significant proportion of early-onset as against late-onset CRC in India. In addition, KRAS mutation frequency was significantly lower in early-onset CRC indicating that a significant proportion of CRC in India may follow tumorigenesis pathways distinct from the classical CRC progression sequence. Our study has therefore revealed the possible existence of non-canonical tumorigenesis pathways in early-onset CRC in India.

PNUTS functions as a proto-oncogene by sequestering PTEN.

PTEN is a well-defined tumor suppressor gene that antagonizes the PI3K/Akt pathway to regulate a multitude of cellular processes, such as survival, growth, motility, invasiveness, and angiogenesis. While the functions of PTEN have been studied extensively, the regulation of its activity during normal and disease conditions still remains incompletely understood. In this study, we identified the protein phosphatase-1 nuclear targeting subunit PNUTS (PPP1R10) as a PTEN-associated protein. PNUTS directly interacted with the lipid-binding domain (C2 domain) of PTEN and sequestered it in the nucleus. Depletion of PNUTS leads to increased apoptosis and reduced cellular proliferation in a PTEN-dependent manner. PNUTS expression was elevated in certain cancers compared with matched normal tissues. Collectively, our studies reveal PNUTS as a novel PTEN regulator and a likely oncogene.

Pseudoaneurysm of left colic artery after Tenckhoff catheter removal, with unrecognized fungal peritonitis.

A 42-year-old continuous ambulatory peritoneal dialysis patient had presented to us with symptoms and signs of peritonitis, complicated by intestinal obstruction. On fourth day after admission, the Tenckhoff catheter was removed, as there was no response to intraperitoneal antibiotic. He developed hypotension during one of the hemodialysis sessions and was found to have low hemoglobin of 4 g/dL. Computed tomography revealed high-density fluid suggestive of fresh blood and clots in the peritoneal cavity. Conventional visceral angiogram with selective inferior mesenteric arterial cannulation revealed pseudoaneurysm arising from the descending branch of the left colic artery. An effort to embolize the pseudoaneurysm failed on 2 occasions. At laparotomy the pseudoaneurysm of the left colic artery was identified after evacuation of blood clots. The pseudoaneurysm was then excised and a lateral rent in the descending branch of left colic artery was repaired. The pus showed septate hyphae on potassium hydroxide mount. He was treated with injections of amphotericin B and oral voriconazole as the culture showed growth of Aspergillus flavus. The early fibrinous, ''easy'' flimsy adhesions formed during the initial intestinal obstruction phase might have resulted in formation of the pseudoaneurysm when the Tenckhoff catheter was removed with traction. The removal of the Tenckhoff catheter, drop in hemoglobin and distension of the abdomen were temporally so closely related that the pseudoaneurysm as a result of the traction removal of the catheter was undeniable. A controlled trial would provide firm evidence either in favor or against formal dissection for the removal of Tenckhoff catheters.

Central pancreatectomy for neoplasm of mid pancreas - a report of four cases.

Central pancreatectomy (CP) originally done for pancreatic trauma and focal pancreatitis is recently being performed for benign and low grade malignant neoplasm of mid pancreas. It offers the advantage of conserving pancreatic tissue and preserving gastroduodenal-biliary anatomy, important for maintenance of endocrine and exocrine pancreatic function. We reviewed our database between Jan. 2005 and June 2007. Four patients (2 males and 2 females) in the age range of 12 to 55 years underwent CP for a mass in the mid pancreas. Two were known diabetic. Histology reported solid variant of serous cystadenoma (1), solid pseudopapillary tumor (1), focal pancreatitis (1) and ductal adenocarcinoma (1). Postoperatively one patient had transient pancreatic fistula which was managed conservatively. There was no mortality. On follow-up (7 to 43 months) none of the patients required enzyme supplements and diabetes did not worsen. Patient with ductal adenocarcinoma progressed within 7 months. CP may be a viable option for mid pancreatic lesions of benign or low grade malignant potential.

Postcholecystectomy surgical site infection by Salmonella enterica var. Weltevreden.

BACKGROUND: Surgical site infections (SSI) are the most common complication of gastrointestinal surgery. The most common endogenous organisms encountered are the enteric pathogens. METHODS: We report a rare case of S. enterica var. Weltevreden as a cause of SSI after cholecystectomy and common bile duct exploration. Pertinent literature is reviewed. RESULTS: The infection was due to bile spillage and contamination during surgery. The organism was found to be sensitive only to imipenem, and the patient recovered following intravenous treatment with that carbapenem. CONCLUSIONS: This case illustrates the fact that cholecystectomy with bile spillage is a definite risk factor for SSI. Although controversial, isolation of the pathogen from the bile and the surgical site must be made to allow this rare pathogen to be identified. Appropriate antibiotic could then be directed against the pathogen.