Savio George Barreto

Justifying vein resection with pancreatoduodenectomy

Interest in radical surgery to achieve complete resection and improve long-term survival in patients undergoing pancreatoduodenectomy for ductal adenocarcinoma has been renewed. This surgery includes extended lymphadenectomy, multivisceral resections, and synchronous arterial and venous resections. The evidence that these surgeries improve long-term survival is poor, except perhaps for synchronous venous resection, which can be justified if a margin negative (R0) resection is achieved without increased morbidity and mortality, and if there is no invasion of the vein wall. The recognition of patients with borderline resectable pancreatic cancer and the increasing use of neoadjuvant treatment makes it more difficult to know if the vein is invaded, increases reliance on trial dissection to establish resectability, and might increase the number of synchronous venous resections done. This Personal View seeks to review the justification for pancreatoduodenectomy with synchronous venous resection to promote debate and draw attention to the gaps in knowledge for further research.

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.

How does cigarette smoking cause acute pancreatitis

INTRODUCTION Acute Pancreatitis (AP) is an emerging health problem world-wide and it is a major cause of admissions for gastrointestinal disease in many countries. Amongst the more common causes (alcohol and gallstones), recent evidence has emerged indicating that smoking is an independent risk factor for AP. However, the mechanisms involved in smoking-induced AP have not been completely elucidated. This review puts together all the published evidence in literature to present the clinical and laboratory evidence relating smoking to the causation of AP. DISCUSSION The two main metabolites from cigarette smoke, namely nicotine and NNK are able to induce functional and histological changes within the pancreas consistent with AP. The major mechanisms involved include their action on acinar cells and zymogen secretion through pathways involving CCK and the nicotinic preganglionic receptors. Effects on the pancreatic microvasculature may be mediated through the nitric oxide pathway. There is indirect evidence to suggest that nicotine and acrolein may lead to CFTR dysfunction thereby influencing ductal secretion. However, direct evidence for this effect is needed. The effect of cigarette smoke metabolites on stellate cells and the islets warrants further investigation in the context of pathogenesis of AP. CONCLUSION Using a step-wise approach, the review revisits the effects of the various metabolites of cigarette smoke on the constituents of the pancreas (exocrine, endocrine, neurohormonal, stellate cells, ductal system) and highlights their proven, and potential, mechanisms in triggering off an attack of AP.

Vitamin D and pancreatic cancer

Pancreatic cancer is currently the fourth leading cause of cancer-related death, and it is projected that within the next two decades it will become the second most common cause of death due to cancer. Few patients are diagnosed when surgical resection is feasible and the efficacy of existing chemotherapeutic agents for advanced/metastatic cancer is limited. Thus, there is a need to identify agents that can prevent pancreatic cancer or improve survival in those affected. Vitamin D and its analogues, with their ability to regulate cell growth, differentiation, apoptosis and angiogenesis, may be promising agents. This review explores the published literature about the potential role of vitamin D and its analogues in preventing or treating pancreatic cancer. The vitamin D system is altered in pancreatic cancer. Pancreatic cancer tissue expresses vitamin D receptors, but the calcitriol analogues may affect pancreatic cancer tissue by mechanisms that do not involve interaction with its receptors. Experimental evidence postulates multiple potential mechanisms by which calcitriol analogues may exert their anti-cancer effect, the most common being by action on cyclin-dependent kinases p21 and p27. Use of calcitriol analogues in pancreatic cancer remains largely underexplored and warrants further clinical trials.

Pancreatoduodenectomy - Preventing Complications

Increased awareness of periampullary & pancreatic head cancers, and the accompanying improved outcomes following pancreatoduodenectomy (PD), has possibly led to an increase in patients seeking treatment for the same. While there has definitely been a reduction in morbidity rates following PD in the last few decades, this decline has not mirrored the drastic fall in mortality. Amongst the foremost in the factors responsible for this reduction in mortality is the standardization of surgical technique and development of dedicated teams to manage all aspects of this demanding procedure. This review intends to provide the reader with an overview of major complications following this major surgery and measures to prevent them based on the authors’ experience.

Non-typhoidal Salmonella DNA traces in gallbladder cancer

BackgroundWe earlier proposed a genetic model for gallbladder carcinogenesis and its dissemination cascade. However, the association of gallbladder cancer and ‘inflammatory stimulus’ to drive the initial cascade in the model remained unclear. A recent study suggested infection with Salmonella can lead to changes in the host signalling pathways in gallbladder cancer.FindingsWe examined the whole exomes of 26 primary gall bladder tumour and paired normal samples for presence of 143 HPV (Human papilloma virus) types along with 6 common Salmonella serotypes (S. typhi Ty2, S. typhi CT18, S. typhimurium LT2, S. choleraesuis SCB67, S. paratyphi TCC, and S. paratyphi SPB7) using a computational subtraction pipeline based on the HPVDetector, we recently described. Based on our evaluation of 26 whole exome gallbladder primary tumours and matched normal samples: association of typhoidal Salmonella species were found in 11 of 26 gallbladder cancer samples, and non-typhoidal Salmonella species in 12 of 26 gallbladder cancer, with 6 samples were found co-infected with both.ConclusionsWe present the first evidence to support the association of non-typhoidal Salmonella species along with typhoidal strains in gallbladder cancer. Salmonella infection in the chronic carrier state fits the role of the ‘inflammatory stimulus’ in the genetic model for gallbladder carcinogenesis that may play a role in gallbladder cancer analogous to Helicobacter pylori in gastric cancer.

The cost of Pancreatoduodenectomy – An analysis of clinical determinants

BACKGROUND Health care spending is increasing the world over. Determining preventable or correctable factors may offer us valuable insights into developing strategies aimed at reducing costs and improving patient care. The aim of this study was to conduct an exploratory analysis of clinical factors influencing costs of Pancreatoduodenectomy (PD). METHODS The financial and clinical records of 173 consecutive patients who underwent PD at a tertiary care referral centre, between January 2013 and June 2015 were analysed. RESULTS Complications, by themselves, did not increase costs associated with PD unless they resulted in an increase in the duration of stay more than 11 days. Intraoperative blood transfusion (p-.098) and performance of an end-to-side PJ (p-.043) were independent factors significantly affecting costs. Synchronous venous resections significantly increased costs (p-.006) without affecting duration of stay. Advancing age, hypertension, neurological and respiratory disorders, preoperative endoscopic retrograde cholangiopancreatography (ERCP), performance of a feeding jejunostomy, and surgical complications eg PPH, POPF and DGE significantly increased the duration of stay sufficient enough to influence costs of PD. CONCLUSIONS It is not the merely the development, but severity of complications that significantly increase the cost of PD by increasing hospital stay. Strategies aimed at reducing intraoperative blood transfusion requirement as well as minimising the development of POPF can help reduce costs. Synchronous venous resections significantly increase costs independent of hospital stay. This study identified nine factors that may be included in the development of a preoperative nomogram that could be used in preoperative financial counselling of patients undergoing PD.

To improve outcomes of gallbladder cancer we need to better understand it

The famous and most revered Chinese Philosopher, Lao Tzu once said, ‘ A journey of a thousand miles begins with a single step ’. The words of this wise man hold true for every sphere of life, and certainly medicine is not excluded.

The fight against cancer: Is it worthwhile?

This article alludes to the findings of Tomasetti and Vogelstein and argues that for clinicians and scientists no matter how difficult understanding the pathogenesis of cancer may be, they remain the only hope for patients suffering from the disease. Data citing wide differences in cancer incidence in different parts of the world is presented to drive home the point that ′Bad luck′ is not a good enough explanation for cancer pathogenesis. There remains a lot to be uncovered in cancer and clinicians and scientists should strive to this end.

Indian Council of Medical Research consensus document for the management of gastrointestinal stromal tumors

EXECUTIVE SUMMARY This consensus statement was produced along with the gastric cancer discussions as stomach is the most common site for gastrointestinal stromal tumor (GIST). The recommendations apply to treatment of GIST. Evaluation of a patient with newly diagnosed GIST should include essential tests: A standard white light endoscopy with 6-8 biopsies (c-KIT testing on immunohistochemistry) from the tumor for confirmation of the diagnosis, a computed tomography (CT) scan (multi-detector or helical) of the abdomen and pelvis for staging with a CT chest or chest X-ray, and complete blood counts, renal function tests and liver function tests. Endoscopic ultrasonography (EUS)/magnetic resonance imaging (MRI)/positron emission tomography (PET)-CT are not recommended for all patients. For localized and resectable disease, surgery is recommended. The need for adjuvant treatment with imatinib would be guided by the risk stratification on the histopathological analysis of the resected specimen. For localized but borderline resectable tumors, upfront surgery may be considered only if complications due to the tumor are present such as major bleeding or gastric outlet obstruction. In all other patients, neoadjuvant imatinib should be considered to downstage the disease followed by surgery (with a curative intent, if feasible) in those with stable or partial response. This may be followed by adjuvant imatinib. In those patients with a poor response, further imatinib with dose escalation or sunitinib may be considered. Patients with metastatic disease must be assessed for treatment with imatinib as first-line therapy followed by sunitinib as second-line therapy versus best supportive care on an individual basis.