Ashwin Rammohan

A gist of gastrointestinal stromal tumors: A review.

Gastrointestinal stromal tumors (GISTs) have been recognized as a biologically distinctive tumor type, different from smooth muscle and neural tumors of the gastrointestinal tract (GIT). They constitute the majority of gastrointestinal mesenchymal tumors of the GIT and are known to be refractory to conventional chemotherapy or radiation. They are defined and diagnosed by the expression of a proto-oncogene protein detected by immunohistochemistry which serves as a crucial diagnostic and therapeutic target. The identification of these mutations has resulted in a better understanding of their oncogenic mechanisms. The remarkable antitumor effects of the molecular inhibitor imatinib have necessitated accurate diagnosis of GIST and their distinction from other gastrointestinal mesenchymal tumors. Both traditional and minimally invasive surgery are used to remove these tumors with minimal morbidity and excellent perioperative outcomes. The revolutionary use of specific, molecularly-targeted therapies, such as imatinib mesylate, reduces the frequency of disease recurrence when used as an adjuvant following complete resection. Neoadjuvant treatment with these agents appears to stabilize disease in the majority of patients and may reduce the extent of surgical resection required for subsequent complete tumor removal. The important interplay between the molecular genetics of GIST and responses to targeted therapeutics serves as a model for the study of targeted therapies in other solid tumors. This review summarizes our current knowledge and recent advances regarding the histogenesis, pathology, molecular biology, the basis for the novel targeted cancer therapy and current evidence based management of these unique tumors.

Hemosuccus Pancreaticus: 15-Year Experience from a Tertiary Care GI Bleed Centre

Background. Hemosuccus pancreaticus (HP) is a very rare and obscure cause of upper gastrointestinal bleeding. Due to its rarity, the diagnostic and therapeutic strategy for the management of this potentially life threatening problem remains undefined. The objective of our study is to highlight the challenges in the diagnosis and management of HP and to formulate a protocol to effectively and safely manage this condition. Methods. We retrospectively reviewed the records of all patients who presented with HP over the last 15 years at our institution between January 1997 and December 2011. Results. There were a total of 51 patients with a mean age of 32 years. Nineteen patients had chronic alcoholic pancreatitis; twenty-six, five, and one patient had tropical pancreatitis, acute pancreatitis, and idiopathic pancreatitis, respectively. Six patients were managed conservatively. Selective arterial embolization was attempted in 40 of 45 (89%) patients and was successful in 29 of the 40 (72.5%). 16 of 51 (31.4%) patients required surgery. Overall mortality was 7.8%. Length of followup ranged from 6 months to 15 years. Conclusions. Upper gastrointestinal bleeding in a patient with a history of chronic pancreatitis could be caused by HP. All hemodynamically stable patients with HP should undergo prompt initial angiographic evaluation, and if possible, embolization. Hemodynamically unstable patients and those following unsuccessful embolization should undergo emergency haemostatic surgery. Centralization of GI bleed services along with a multidisciplinary team approach and a well-defined management protocol is essential to reduce the mortality and morbidity of this condition.

Synbiotics in Surgery for Chronic Pancreatitis: Are They Truly Effective? A Single-blind Prospective Randomized Control Trial

BACKGROUND Postoperative infectious complications in patients undergoing pancreatic surgery are a significant cause for morbidity and mortality. Although synbiotics have beneficial effects on human health, their clinical value in surgical patients remains unclear given a paucity of applicable clinical studies. AIM To determine the impact of perioperative synbiotic therapy on postoperative infectious complications, morbidity and mortality in patients undergoing pancreatic surgery for chronic pancreatitis. METHODS A trial was conducted in patients with chronic calcific pancreatitis undergoing Freys procedure. Group A received a specific synbiotic composition, 5 days prior and 10 days after the surgery. Group B received a placebo. Primary study endpoint was the occurrence of postoperative infection during the first 30 days. Secondary outcome measures were mortality, length of hospital stay, days in intensive care unit, and duration of antibiotic therapy. Using previously accrued data, with α of 0.05 and power 80%, the sample size was calculated as 35 patients for each group with a dropout rate of 10%. RESULTS Of the 79 patients enrolled, 75 completed the trial [group A (n = 39) and group B (n = 36)]. The incidence of postoperative infectious complications (12.8% vs 39%; P < 0.05), duration of antibiotics therapy (P < 0.05), and length of hospital stay (P < 0.05) were significantly lower in the synbiotic group. CONCLUSIONS Synbiotics significantly reduce septic complications, hospital stay, and antibiotic requirement in patients undergoing pancreatic surgery for chronic pancreatitis. Furthermore, basic and clinical research would clarify the underlying mechanisms of their therapeutic effect and define the appropriate conditions for use.

Bile duct thrombi in hepatocellular carcinoma: is aggressive surgery worthwhile?

INTRODUCTION Obstructive jaundice as a result of bile duct tumour thrombus (BDTT) is an unusual clinical entity and an uncommon presenting feature of hepatocellular carcinoma (HCC). This study evaluates the outcome of hepatectomy for HCC with obstructive jaundice as a result of BDTT in non-cirrhotic livers. METHODS Between 1997 and 2012, out of 426 patients with HCC in non-cirrhotic livers, 39 patients with BDTT (Group I n = 39), who underwent a hepatectomy, were analysed and compared with the non-BDTT group (Group II n = 387). RESULTS The demographic profile and biochemical parameters between Group I and Group II were compared; apart from the presence of jaundice at presentation and an elevated serum bilirubin, there were no significant differences. Post-operative morbidity and mortality were 11 (28.2%) and 2 (5.1%), respectively, in Group I. There were no differences between the groups with regards to the operative variables and short-term outcomes. The 1-, 3- and 5-year survival rates in Group I were 82%, 48% and 10%, respectively, with a median survival of 28.6 months and were significantly poorer than Group II (90%, 55% and 38%, respectively, with a median survival of 39.2 months). CONCLUSION The mere presence of BDTT in HCC does not indicate an advanced or inoperable lesion. When technically feasible, a formal hepatic resection is the preferred first-line treatment option in these patients.

Implications of the presence of an aberrant right hepatic artery in patients undergoing pancreaticoduodenectomy.

AIM To analyze the differences in outcomes and the clinical impact following pancreatoduodenectomy (PD) in patients with and without aberrant right hepatic artery (aRHA). METHODS All patients undergoing PD between January 2008 and December 2012 were divided into two groups, one with aRHA and the other without. These groups were compared to identify differences in the intraoperative variables, the oncological clearance and the postoperative morbidity, mortality and hospital stay. RESULTS A total of 225 patients underwent PD, of which 43 (19.1%) patients were found to have either accessory or replaced right hepatic arteries (aRHA group). The aRHA was preserved in 79% of the patients. There was no significant difference in the intraoperative blood loss but operative time was prolonged, reflecting the complexity of the procedure [420 ± 44 (240-540) min vs 480 ± 45 (300-600) min, P < 0.05)]. There were no differences in the incidence of postoperative complications (pancreatic leak, pancreatic fistula, delayed gastric emptying and mortality) and hospital stay. Oncological clearance in the form of positive resection margins [13 (7.1%) vs 3 (6.9%)] and lymph node yield were also similar in the two groups. CONCLUSION An aRHA is found in approximately one fifth of patients undergoing PD. Preservation is technically possible in most patients and can increase the operative complexity but does not negatively affect the safety or oncological outcomes of the procedure.

Xanthogranulomatous Cholecystitis Masquerading as Gallbladder Cancer: Can It Be Diagnosed Preoperatively?

Background. Xanthogranulomatous cholecystitis (XGC) is often misdiagnosed as gallbladder cancer (GBC). We aimed to determine the preoperative characteristics that could potentially aid in an accurate diagnosis of XGC masquerading as GBC. Methods. An analysis of patients operated upon with a preoperative diagnosis of GBC between January 2008 and December 2012 was conducted to determine the clinical and radiological features which could assist in a preoperative diagnosis of XGC. Results. Out of 77 patients who underwent radical cholecystectomy, 16 were reported as XGC on final histopathology (Group A), while 60 were GBC (Group B). The incidences of abdominal pain, cholelithiasis, choledocholithiasis, and acute cholecystitis were significantly higher in Group A, while anorexia and weight loss were higher in Group B. On CT, diffuse gallbladder wall thickening, continuous mucosal line enhancement, and submucosal hypoattenuated nodules were significant findings in Group A. CT findings on retrospect revealed at least one of these findings in 68.7% of the cases. Conclusion. Differentiating XGC from GBC is difficult, and a definitive diagnosis still necessitates a histopathological examination. An accurate preoperative diagnosis requires an integrated review of clinical and characteristic radiological features, the presence of which may help avoid radical resection and avoidable morbidity in selected cases.

Transpancreatic Hepatomesenteric Trunk Complicating Pancreaticoduodenectomy

CONTEXT Standard celiac and hepatic arterial anatomy occur in approximately 60% of the patients; for the remaining, multiple variations have been described. A thorough knowledge of these anomalies is important in order to avoid unnecessary complications. In this report we describe one of the rarest arterial anomalies, a hepatomesenteric trunk supplying the liver. We attempt to elucidate its implications pertaining to the safe performance of a pancreaticoduodenectomy. CASE REPORT A 45-year-old male with a one-month duration painless progressive jaundice was evaluated and diagnosed as having a periampullary growth. Preoperative imaging did not suggest any arterial anomalies. Intraoperatively, the common hepatic artery was found to originate from the superior mesenteric artery. He underwent a pylorus preserving pancreaticoduodenectomy with a meticulous dissection and preservation of the aberrant hepatomesenteric trunk. His postoperative period was uneventful and is doing well on follow up. CONCLUSION Variations in hepatic and celiac arterial anatomy are common, and may not get picked up on preoperative imaging. A high index of suspicion in every patient along with a precise knowledge of the normal anatomy and awareness of the aberrant anatomy is a sine qua non to the performance of a safe pancreaticoduodenectomy.

Pembrolizumab for metastatic hepatocellular carcinoma following live donor liver transplantation: The silver bullet?

Treatment options for hepatocellular carcinoma (HCC) recurrence following liver transplantation (LT) are extremely limited. HCCs are a heterogenous group of tumors driven by inflammation and hence the rationale to evaluate immunotherapy in these patients. The immune checkpoint protein, programmed death receptor 1 (PD-1), is an inhibitory molecule expressed on the surface of multiple tissue types and keeps T cells from attacking tumor cells. We report on a case of metastatic HCC following LT that responded dramatically to pembrolizumab, a PD-1 inhibitor, after failure of therapy with sorafenib.

Impact of perioperative enteral synbiotics in hepatic and pancreatic surgery: design and rationale of a single blind placebo controlled prospective randomised control trial

Background Prebiotics and probiotics influence all pathogenic mechanisms of bacterial translocation. Used in combination, they are called synbiotics. Postoperative infective complications in patients undergoing hepatic and pancreatic surgery lead to a significant prolongation of hospital stay and increased costs. While synbiotics are considered to have beneficial effects on human health, their clinical value in surgical patients, especially in South Asia remains unclear given a paucity of applicable clinical studies. In this study we aim to assess their clinical usefulness in patients who undergo hepatic and pancreatic surgery. Methods A prospective monocentric randomised single blind controlled trial is being conducted in patients undergoing major pancreatic resections (Whipple procedure, distal pancreatectomy, Frey procedure) and hepatic resections. Group A received a specific synbiotic composition, 5 days prior and 10 days after the surgery. Group B received a placebo. Primary study end point was the occurrence of postoperative infection during the first 30 days. Secondary outcome measures were mortality, first bowel movement, days in intensive care unit, length of hospital stay, and duration of antibiotic therapy. Side effects of probiotics were evaluated. From previous studies we assumed that perioperative synbiotics reduce the proportion of patients with infectious complications from 50% to 12%, with α of 0.05 and power 80%, the calculated sample size was 35 patients for each group with a dropout rate of 10%. Conclusions This study is intended at determining the impact of perioperative synbiotic therapy on postoperative infectious complications, morbidity and mortality in patients undergoing major pancreatic and hepatic surgery. Clinical trial The Clinical Trials Registry of India (CTRI/2013/06/003737).

Inflammatory pseudotumour secondary to spilled intra-abdominal gallstones

INTRODUCTION Spillage of calculi in the abdomen is frequent during Laparoscopic Cholecystectomy (LC). Though uncommon, these stones may lead to early or late complications. We describe a rare case of spilled gallstone presenting four years after the index procedure, with a mass in the parietal wall mimicking a neoplastic lesion. PRESENTATION OF CASE A 50 year old male presented with a mass in the right upper quadrant for the past 2 years. His past surgical history included a LC done four years ago. Intraoperative procedural details of the surgery were not available. A Computed Tomography (CT) scan showed an extrahepatic mass in the subdiaphragmatic space extending onto the soft tissues of the parietal wall. He underwent laparoscopic piecemeal excision of this organized mass. His post operative period was uneventful and he was pain-free on follow up. DISCUSSION Gallbladder perforation can occur due to excessive traction during retraction or during dissection from the liver bed. It can also occur during extraction from the abdomen. Infected bile, pigment gallstones, male gender, advanced age, perihepatic location of spilled gallstones, more than 15 gallstones and an average size greater than 1.5cm have been identified as risk factors for complications. Definitive treatment is surgery with excision of the organized inflammatory mass and extraction of gallstones to avoid future recurrence. CONCLUSION Spilled gallstones can be a diagnostic challenge and can cause significant morbidity to the patient. Clear documentation of spillage and explanation to the patient is of utmost importance, as this will enable prompt recognition and treatment of any complications. Prevention of spillage is the best policy.