Meta-analysis of an artery-first approach versus standard pancreatoduodenectomy on perioperative outcomes and survival.

BACKGROUND: The aim of this systematic review and meta-analysis was to evaluate perioperative outcomes and survival in patients undergoing an artery-first approach to pancreatoduodenectomy in comparison with those having standard pancreatoduodenectomy. METHODS: A systematic search of PubMed, MEDLINE, Embase and the Cochrane Database of Systematic Reviews was performed in accordance with PRISMA guidelines. Comparative studies including patients who underwent artery-first pancreatoduodenectomy and standard pancreatoduodenectomy were analysed. RESULTS: Seventeen studies were included in the final analysis. There were 16 retrospective cohort or case-control studies and one RCT. A total of 1472 patients were included in the meta-analysis, of whom 771 underwent artery-first pancreatoduodenectomy and 701 had standard pancreatoduodenectomy. Intraoperative blood loss (mean difference -389 ml; P < 0·001) and the proportion of patients requiring intraoperative transfusion (10·6 per cent (54 of 508) versus 40·1 per cent (186 of 464); P < 0·001) were significantly lower in the artery-first group. Although rates of perioperative mortality were comparable between the two groups, perioperative morbidity (35·5 per cent (263 of 741) versus 44·3 per cent (277 of 625); P = 0·002), and the incidence of grade B/C pancreatic fistula (7·4 per cent (26 of 353) versus 12·8 per cent (42 of 327); P = 0·031) were significantly lower in the artery-first group. The R0 resection rate (75·8 per cent (269 of 355) versus 67·0 per cent (280 of 418); P < 0·001) and overall survival (hazard ratio 0·72, 95 per cent c.i. 0·60 to 0·87; P < 0·001) were significantly higher in the artery-first group. CONCLUSION: The artery-first approach to pancreatoduodenectomy may be associated with improved perioperative outcomes and survival.

Bursectomy for gastric cancer: What does the evidence indicate?

Radical resection of the bursa omentalis (radical bursectomy) as part of a curative resection for gastric cancer has been advised for close to a century. However, the postulated associated morbidity and lack of a clear benefit in terms of survival preclude its routine use. To objectively review the available evidence on the role of bursectomy as part of a curative resection for gastric cancer. A systematic search of the scientific literature was carried out using Embase, PubMed, MedLine and the Cochrane central register of controlled trials for the years 1965-2013 to obtain access to all publications, especially randomized controlled trials (RCTs), systematic reviews and meta-analyses involving bursectomy in gastric cancer with the appropriate specific search terms, namely, "bursectomy," "stomach cancer," "gastric cancer," "survival," "morbidity," "outcomes" and "RCTs". Using the above search strategy, a total of 29 publications was retrieved of which five publications were identified describing bursectomy and its outcomes in gastric cancer. These included three retrospective cohort studies and two publications from a single RCT. Bursectomy do not appear to add the morbidity or mortality of the overall surgery. However, it did not appear to significantly improve overall survival neither in the retrospective cohort studies nor in the only RCT. The evidence to date is insufficient to suggest any additional benefit of routine bursectomy to a radical gastrectomy with D2 lymphadenectomy for gastric cancer. Results of an on-going RCT are awaited to determine if bursectomy may further improve overall survival in patients with advanced T-stage of disease.

A genetic model for gallbladder carcinogenesis and its dissemination.

Gallbladder cancer, although regarded as the most common malignancy of the biliary tract, continues to be associated with a dismal overall survival even in the present day. While complete surgical removal of the tumour offers a good chance of cure, only a fraction of the patients are amenable to curative surgery owing to their delayed presentation. Moreover, the current contribution of adjuvant therapies towards prolonging survival is marginal, at best. Thus, understanding the biology of the disease will not only enable a better appreciation of the pathways of progression but also facilitate the development of an accurate genetic model for gallbladder carcinogenesis and dissemination. This review provides an updated, evidence-based model of the pathways of carcinogenesis in gallbladder cancer and its dissemination. The model proposed could serve as the scaffolding for elucidation of the molecular mechanisms involved in gallbladder carcinogenesis. A better understanding of the pathways involved in gallbladder tumorigenesis will serve to identify patients at risk for the cancer (and who thus could be offered prophylactic cholecystectomy) as well as aid oncologists in planning the most suitable treatment for a particular patient, thereby setting us on the vanguard of transforming the current treatment paradigm for gallbladder cancer.

Galanin receptor 3--a potential target for acute pancreatitis therapy.

BACKGROUND: Galanin participates in the pathogenesis of acute pancreatitis (AP). The galanin receptor (GALR) sub-types involved, however, are unclear. We aimed to determine GALRs messenger RNA (mRNA) expression in mouse pancreas, describe their localization, and ascertain if GALR2 and GALR3 are involved in AP. METHODS: Galanin receptor expression in murine whole pancreas, acinar, and islet cells was quantified by polymerase chain reaction amplification of reverse-transcribed RNA for mRNA, Western blot analysis for protein and in situ hybridization for GALR localization. Isolated acinar cells were used to determine galanin's effect on amylase secretion. Acute pancreatitis was induced in mice by caerulein injections. Mice, with and without AP, were treated with the highly selective GALR2 antagonist M871, or the specific GALR3 antagonist SNAP-37889. Indices of AP were measured at 12 h. KEY RESULTS: Murine pancreas expresses mRNA for GALRs. In islets the expression of all GALR are comparable, whereas in acinar cells GALR3 is predominantly expressed. Western blot analysis confirmed that the GALR proteins are expressed by acinar cells. In situ hybridization analysis confirmed that GALR3 mRNA is present in islet and acinar cells, while mRNA for GALR1 and 2 is confined to islets. Galanin did not influence basal and caerulein-stimulated amylase release from acinar cells. M871 treatment reduced some, whereas SNAP-37889 treatment reduced all indices of AP (by 40-80%). CONCLUSIONS & INFERENCES: Galanin receptor mRNA and protein are expressed in mouse pancreas, with GALR3 mRNA predominating. GALR3 antagonism reduced the severity of AP whereas GALR2 antagonism was less effective. GALR3 is a potential target for treatment of AP.

Cholelithiasis in gallbladder cancer: coincidence, cofactor, or cause!

BACKGROUND: While gallstones are associated with cancers of the gallbladder, the actual nature of their relationship needs to be clarified. This would aid the recommendations on the need for prophylactic cholecystectomy. METHODS: A systematic search of the scientific literature was carried out using the Medline, the Embase, and the Cochrane Central Register of Controlled Trials for the years 1891-2009 to obtain access to all publications involving gallstones in gallbladder cancer. RESULTS: While some epidemiological evidence supports a causal relationship for gallstones in gallbladder cancer, other studies have demonstrated a relatively low incidence of gallbladder cancer in countries reporting a high incidence of gallstones as a whole. In those studies where gallstones appear to have a causative role for cancer, the risk increases with increasing size, volume and weight, and number of the stones. The impact of duration of the stone or its composition is not clear. Experimental evidence from studies examining the impact of artificially introducing gallstones in the gallbladder has failed to lead to carcinogenesis. CONCLUSIONS: The evidence at the current time indicates that gallstones are a cofactor in the causation of gallbladder cancer. Absolute proof of their role as a cause for gallbladder cancer is lacking. The recommendation for prophylactic cholecystectomy in countries reporting a high incidence of gallbladder cancer and associated gallstones needs to be tailored to the epidemiological profile of the place.

Galanin receptor antagonist m35 but not m40 or c7 ameliorates cerulein-induced acute pancreatitis in mice.

BACKGROUND/AIMS: We compared the galanin antagonists C7, M35, M40 and galantide, for their ability to ameliorate acute pancreatitis (AP). METHODS: Galanin antagonists were co-administered with 7 hourly cerulein injections used to induce AP. Plasma amylase and lipase activities were measured as indices of AP, and pancreata were harvested at 12 h for histological examination and estimation of myeloperoxidase (MPO) activity. RESULTS: Treatment with galantide, M35 and C7 ameliorated the AP-induced plasma hyperenzymemia by 40-75%. Administration of M40 did not significantly alter plasma hyperenzymemia. Galantide, M35 and M40 significantly reduced the pancreatic MPO activity by 65-80%, whereas C7 increased MPO activity. Galantide and M35 but not C7 or M40 treatment significantly reduced the AP-induced necrosis score by 30-50% compared to the AP alone group. C7 alone increased plasma lipase activity and the pancreatic necrosis score compared with saline treatment alone, whereas the other antagonists were without effect. CONCLUSION: Galantide and M35 ameliorated the severity of AP, but M40 and C7 had mixed effects. Complex galanin pathways may be involved in cerulein-induced AP. M35 and galantide are potential therapeutic peptides for the treatment of AP and further evaluation should be considered. and IAP.

Colovesical fistula following an open preperitoneal "Kugel" mesh repair of an inguinal hernia.

Erosion of the "Kugel" mesh into intraperitoneal organs has not been previously reported in the medical literature. We report such an occurrence in a 54-year-old male, 4 years following a "Kugel" preperitoneal repair of a left-sided inguinal hernia. The patient presented with septicaemia, pneumaturia and left iliac fossa pain. His computed tomography (CT) scan indicated the presence of gas in the bladder and a thickened loop of sigmoid colon attached to the region of the dome of the bladder. Colonoscopy showed some scattered diverticula in the sigmoid colon but no tumour. On surgical exploration, the "Kugel" mesh was found to erode the sigmoid colon and the bladder wall, leading to a colovesical fistula. An anterior resection of the rectum with removal of the mesh with closure of the bladder wall defect was performed.

Defining the role of surgery for complications after pancreatoduodenectomy.

BACKGROUND: Although mortality rates following pancreatoduodenectomy have drastically reduced over the last few decades, high morbidity rates have continued to trouble pancreatic surgeons across the world. Interventional radiology has reduced the need for re-exploration for complications following pancreatoduodenectomy. There remain specific indications for re-exploration in such scenarios. It is thus pertinent to identify those clinical scenarios where surgery still has a role in managing complications of pancreatoduodenectomy. The aim of the study was to define the role of surgery for dealing with complications following pancreatoduodenectomy. METHODS: One hundred and fifty-seven consecutive pancreatoduodenectomies carried out at a single institution between 1 January 2001 and 28 February 2007, were analysed. The database was looked into to identify patients who underwent re-exploration for complications and to define the indications for the exploration in these patients. RESULTS: Out of the 157 pancreatoduodenectomies, there were, in all, 39 complications (24.2%) in 38 patients. Most of these complications were successfully managed conservatively and with the help of interventional radiology. Seventeen patients had to be re-explored (10.8%). The indications were primarily for haemorrhage, clinically significant pancreatic leaks, biliary leaks, adhesive intestinal obstruction and burst abdomen. The overall mortality rate was 3.1%. The mortality rate in the patients undergoing re-exploration was 11.7%. CONCLUSION: Early haemorrhage (from the pancreatic stump or anastomotic line), clinically significant pancreatic anastomotic leak with discharge from the main wound and an early biliary anastomotic leak are prime indications for re-exploration in patients with complications following pancreatoduodenectomy.

Simultaneous gallbladder and bile duct cancers: revisiting the pathological possibilities.

The pathogenesis of gallbladder cancer presenting synchronously with malignancy of the bile duct has not been clearly understood. The possible causes for the simultaneous presence of these tumors could be due to local spread, metastases, de novo multifocal origin, or as part of a field change in the extrahepatic biliary apparatus. In this article, we discuss the cases of four patients with simultaneous gallbladder and bile duct malignancies and analyze their individual pathologies to provide an explanation into the mechanisms that may play a role in such conditions.

Application of Six Sigma towards improving surgical outcomes.

BACKGROUND/AIMS: Six Sigma is a 'process excellence' tool targeting continuous improvement achieved by providing a methodology for improving key steps of a process. It is ripe for application into health care since almost all health care processes require a near-zero tolerance for mistakes. The aim of this study is to apply the Six Sigma methodology into a clinical surgical process and to assess the improvement (if any) in the outcomes and patient care. METHODOLOGY: The guiding principles of Six Sigma, namely DMAIC (Define, Measure, Analyze, Improve, Control), were used to analyze the impact of double stapling technique (DST) towards improving sphincter preservation rates for rectal cancer. RESULTS: The analysis using the Six Sigma methodology revealed a Sigma score of 2.10 in relation to successful sphincter preservation. This score demonstrates an improvement over the previous technique (73% over previous 54%). CONCLUSIONS: This study represents one of the first clinical applications of Six Sigma in the surgical field. By understanding, accepting, and applying the principles of Six Sigma, we have an opportunity to transfer a very successful management philosophy to facilitate the identification of key steps that can improve outcomes and ultimately patient safety and the quality of surgical care provided.

Acute pancreatitis in Goa--a hospital-based study.

A prospective analysis of the epidemiology and outcome of patients admitted with acute pancreatitis to a tertiary health care centre in Goa was carried out during the time period of 1st June, 2003 to 31st January, 2005. The patients studied were those who were admitted to the Goa Medical College with a diagnosis of acute pancreatitis based on a serum amylase of greater than 180 Somogyii units with appropriate clinical and radiographic evidence. The selection criteria were fulfilled by 282 patients. Acute pancreatitis accounted for 2.29% of all admissions and 4.9% of all deaths in the department of surgery. The disease was seen to affect males more commonly (96.1%), alcohol, being the predominant (92.2%) aetiological factor. The median age for occurrence of the disease was 40 years. Severe acute pancreatitis was encountered in 32.9% cases with a mortality rate of 12.05%. Mortality was higher in patients older than 50 years. Complications included pseudocysts (n = 34), abscess (n = 2), necrosis (n = 6), ascites (n = 13), acute respiratory distress syndrome (n = 13), acute renal failure (n = 14), shock (n = 14), coagulopathy (n = 1) and pleural effusion (n = 26). The widespread availability and use of locally made cheaper varieties of alcohol in our geographical location explains the trend towards alcoholic pancreatitis and younger age groups being affected by the disease.

Laparoscopy in pancreatic tumors.

Recently, increasing number of manuscripts - original articles and case reports have attempted to provide evidence of the forays of minimal access surgery into pancreatic diseases. Many, based on the lack of Level I evidence, still believe that laparoscopy in pancreatic surgery is experimental. This article attempts to look into data exploring the existing use of minimally invasive surgery in pancreatic disease to answer a vital question - what does the evidence say on the current status of laparoscopic surgery in pancreatic tumors.

Is there a role for estrogen and progesterone receptors in gall bladder cancer?

BACKGROUND/AIMS: The concept of metaplastic and non-metaplastic types of gall bladder cancer and the likelihood of hormone receptor expression in the nuclei of tumour cells raised the possibility of a potential role for anti-estrogen therapy in gall bladder cancer. This study was carried out to determine the hormone receptors (ER/PR) expression level in gall bladder cancer using specific immunohistochemical assays and correlate it with patient and tumour histopathological characteristics. PATIENTS AND METHODS: Histopathological tumour specimens of 62 patients who underwent a radical cholecystectomy were analysed. Pronase pretreatment and primary monoclonal antibodies were used to perform immunohistochemical analysis for ER and PR. RESULTS: The histology was adenocarcinoma--predominantly, moderately to poorly differentiated (91%). Gallstones were present in 90% of the individuals. Of the 62 specimens analysed, 62 (100%) and 61 (98%) were negative for ER and PR, respectively. CONCLUSION: The high incidence of gallstone-related gall bladder cancer in India is associated with metaplasia and a tendency to poorer differentiation in the tumour histology. These tumours are consequently less likely to express hormone receptors. Thus, there does not seem to be a role for anti-hormone therapy in patients with histogenesis similar to that seen in India.