Shailesh V. Shrikhande

Borderline resectable pancreatic cancer: A consensus statement by the International Study Group of Pancreatic Surgery (ISGPS)

BACKGROUND This position statement was developed to expedite a consensus on definition and treatment for borderline resectable pancreatic ductal adenocarcinoma (BRPC) that would have worldwide acceptability. METHODS An international panel of pancreatic surgeons from well-established, high-volume centers collaborated on a literature review and development of consensus on issues related to borderline resectable pancreatic cancer. RESULTS The International Study Group of Pancreatic Surgery (ISGPS) supports the National Comprehensive Cancer Network criteria for the definition of BRPC. Current evidence supports operative exploration and resection in the case of involvement of the mesentericoportal venous axis; in addition, a new classification of extrahepatic mesentericoportal venous resections is proposed by the ISGPS. Suspicion of arterial involvement should lead to exploration to confirm the imaging-based findings. Formal arterial resections are not recommended; however, in exceptional circumstances, individual therapeutic approaches may be evaluated under experimental protocols. The ISGPS endorses the recommendations for specimen examination and the definition of an R1 resection (tumor within 1 mm from the margin) used by the British Royal College of Pathologists. Standard preoperative diagnostics for BRPC may include: (1) serum levels of CA19-9, because CA19-9 levels predict survival in large retrospective series; and also (2) the modified Glasgow Prognostic Score and the neutrophil/lymphocyte ratio because of the prognostic relevance of the systemic inflammatory response. Various regimens of neoadjuvant therapy are recommended only in the setting of prospective trials at high-volume centers. CONCLUSION Current evidence justifies portomesenteric venous resection in patients with BRPC. Basic definitions were identified, that are currently lacking but that are needed to obtain further evidence and improvement for this important patient subgroup. A consensus for each topic is given.

The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 Years After

Background. In 2005, the International Study Group of Pancreatic Fistula developed a definition and grading of postoperative pancreatic fistula that has been accepted universally. Eleven years later, because postoperative pancreatic fistula remains one of the most relevant and harmful complications of pancreatic operation, the International Study Group of Pancreatic Fistula classification has become the gold standard in defining postoperative pancreatic fistula in clinical practice. The aim of the present report is to verify the value of the International Study Group of Pancreatic Fistula definition and grading of postoperative pancreatic fistula and to update the International Study Group of Pancreatic Fistula classification in light of recent evidence that has emerged, as well as to address the lingering controversies about the original definition and grading of postoperative pancreatic fistula. Methods. The International Study Group of Pancreatic Fistula reconvened as the International Study Group in Pancreatic Surgery in order to perform a review of the recent literature and consequently to update and revise the grading system of postoperative pancreatic fistula. Results. Based on the literature since 2005 investigating the validity and clinical use of the original International Study Group of Pancreatic Fistula classification, a clinically relevant postoperative pancreatic fistula is now redefined as a drain output of any measurable volume of fluid with an amylase level >3 times the upper limit of institutional normal serum amylase activity, associated with a clinically relevant development/condition related directly to the postoperative pancreatic fistula. Consequently, the former “grade A postoperative pancreatic fistula” is now redefined and called a “biochemical leak,” because it has no clinical importance and is no longer referred to a true pancreatic fistula. Postoperative pancreatic fistula grades B and C are confirmed but defined more strictly. In particular, grade B requires a change in the postoperative management; drains are either left in place >3 weeks or repositioned through endoscopic or percutaneous procedures. Grade C postoperative pancreatic fistula refers to those postoperative pancreatic fistula that require reoperation or lead to single or multiple organ failure and/or mortality attributable to the pancreatic fistula. Conclusion. This new definition and grading system of postoperative pancreatic fistula should lead to a more universally consistent evaluation of operative outcomes after pancreatic operation and will allow for a better comparison of techniques used to mitigate the rate and clinical impact of a pancreatic fistula. Use of this updated classification will also allow for more precise comparisons of surgical quality between surgeons and units who perform pancreatic surgery.

Effect of preoperative biliary stenting on immediate outcome after pancreaticoduodenectomy

Preoperative biliary stenting is associated with bacterial contamination of bile and an increased rate of infectious complications after pancreaticoduodenectomy. Preoperative drainage has been found to have conflicting effects on morbidity and mortality, and no studies have been published on the effect of stent complications and duration of stenting on postoperative outcome. This study examined the effects of preoperative biliary stenting on early outcome after pancreaticoduodenectomy.

Definition of a standard lymphadenectomy in surgery for pancreatic ductal adenocarcinoma: A consensus statement by the International Study Group on Pancreatic Surgery (ISGPS)

BACKGROUND The lymph node (Ln) status of patients with resectable pancreatic ductal adenocarcinoma is an important predictor of survival. The survival benefit of extended lymphadenectomy during pancreatectomy is, however, disputed, and there is no true definition of the optimal extent of the lymphadenectomy. The aim of this study was to formulate a definition for standard lymphadenectomy during pancreatectomy. METHODS During a consensus meeting of the International Study Group on Pancreatic Surgery, pancreatic surgeons formulated a consensus statement based on available literature and their experience. RESULTS The nomenclature of the Japanese Pancreas Society was accepted by all participants. Extended lymphadenectomy during pancreatoduodenectomy with resection of Lns along the left side of the superior mesenteric artery (SMA) and around the celiac trunk, splenic artery, or left gastric artery showed no survival benefit compared with a standard lymphadenectomy. No level I evidence was available on prognostic impact of positive para-aortic Lns. Consensus was reached on selectively removing suspected Lns outside the resection area for frozen section. No consensus was reached on continuing or terminating resection in cases where these nodes were positive. CONCLUSION Extended lymphadenectomy cannot be recommended. Standard lymphadenectomy for pancreatoduodenectomy should strive to resect Ln stations no. 5, 6, 8a, 12b1, 12b2, 12c, 13a, 13b, 14a, 14b, 17a, and 17b. For cancers of the body and tail of the pancreas, removal of stations 10, 11, and 18 is standard. Furthermore, lymphadenectomy is important for adequate nodal staging. Both pancreatic resection in relatively fit patients or nonresectional palliative treatment were accepted as acceptable treatment in cases of positive Lns outside the resection plane. This consensus statement could serve as a guide for surgeons and researchers in future directives and new clinical studies.

‘Artery‐first’ approaches to pancreatoduodenectomy

The technique of pancreatoduodenectomy (PD) has evolved. Previously, non‐resectability was determined by involvement of the portal vein–superior mesenteric vein. Because venous resection can be achieved safely and with greater awareness of the prognostic significance of the status of the posteromedial resection margin, non‐resectability is now determined by involvement of the superior mesenteric artery (SMA). This change, with a need for early determination of resectability before an irreversible step, has promoted the development of an ‘artery‐first’ approach. The aim of this study was to review, and illustrate, this approach.

Pancreatic Anastomoses after Pancreaticoduodenectomy: Do We Need Further Studies?

Pancreatic anastomotic leak is the single most important factor responsible for the considerable morbidity and mortality associated with pancreaticoduodenectomy. Management of the pancreatic remnant is controversially discussed, reflecting the complexity of anastomosing a pancreas of different textures to the digestive tract. A number of studies evaluating diverse options have often provided conflicting conclusions. This information is confusing particularly to those surgeons outside of large-volume centers with broad experience and to general surgeons who perform pancreatic surgery. A PubMed search with the key words pancreaticoduodenectomy, pancreatic anastomosis, pancreaticojejunostomy, pancreaticogastrostomy, and pancreatic fistula was performed. Major series of pancreatic anastomosis published between 1990 and 2002 were studied from diverse centers worldwide. Their results with regard to pancreatic fistula, morbidity, and mortality were documented. Nine series of pancreaticojejunostomy and seven series of pancreaticogastrostomy were evaluated. Eight comparative studies evaluating the two techniques were also analyzed. A single randomized controlled trial was identified among these comparative studies. Equally good results were observed with the two techniques. Other uncommon methods of management of the pancreatic remnant (duct occlusion and ligation) were also evaluated. Pancreaticojejunostomy followed by pancreaticogastrostomy are the most favored techniques. A duct-to-mucosa anastomosis is preferred over other methods. Fistula rates of less than 5%–10% should be the standard irrespective of the technique used. Unlike in the past, mortality can be reduced even in the event of an anastomotic dehiscence, and this aspect is primarily dependent on a meticulous anastomosis based on sound surgical principles rather than the method per se. Based on the information accumulated, adherence to these specific principles could ensure a safe and reliable pancreatic anastomosis with mimimal morbidity and mortality after pancreaticoduodenectomy, even in the hands of general surgeons operating outside high-volume centers.

Global cancer surgery: delivering safe, affordable, and timely cancer surgery

Surgery is essential for global cancer care in all resource settings. Of the 15.2 million new cases of cancer in 2015, over 80% of cases will need surgery, some several times. By 2030, we estimate that annually 45 million surgical procedures will be needed worldwide. Yet, less than 25% of patients with cancer worldwide actually get safe, affordable, or timely surgery. This Commission on global cancer surgery, building on Global Surgery 2030, has examined the state of global cancer surgery through an analysis of the burden of surgical disease and breadth of cancer surgery, economics and financing, factors for strengthening surgical systems for cancer with multiple-country studies, the research agenda, and the political factors that frame policy making in this area. We found wide equity and economic gaps in global cancer surgery. Many patients throughout the world do not have access to cancer surgery, and the failure to train more cancer surgeons and strengthen systems could result in as much as US

Neurokinin-1 Receptor Expression and Its Potential Effects on Tumor Growth in Human Pancreatic Cancer

6.2 trillion in lost cumulative gross domestic product by 2030. Many of the key adjunct treatment modalities for cancer surgery--e.g., pathology and imaging--are also inadequate. Our analysis identified substantial issues, but also highlights solutions and innovations. Issues of access, a paucity of investment in public surgical systems, low investment in research, and training and education gaps are remarkably widespread. Solutions include better regulated public systems, international partnerships, super-centralisation of surgical services, novel surgical clinical trials, and new approaches to improve quality and scale up cancer surgical systems through education and training. Our key messages are directed at many global stakeholders, but the central message is that to deliver safe, affordable, and timely cancer surgery to all, surgery must be at the heart of global and national cancer control planning.

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

The neurokinin-1 receptor (NK-1R) and its ligand substance P (SP) are involved in the pathogenesis of certain neural tumors. Because nerves are significantly altered in pancreatic cancer, evidence for alteration of this pathway in human pancreatic cancer was sought. Expression of NK-1R was analyzed by real-time quantitative RT-PCR, in situ hybridization, immunohistochemistry, and Western blot analysis in normal human pancreatic and pancreatic cancer tissue samples and in pancreatic cancer cell lines. Furthermore, the influence of SP analogs and of the NK-1R antagonist MEN 11467 on pancreatic cancer cell growth was analyzed by sulforhodamine B (SRB) assay. By real-time quantitative RT-PCR, NK-1R mRNA was increased 36.7-fold (p < 0.001) in human pancreatic cancer samples compared with normal controls. Enhanced NK-1R expression levels were not related to tumor grade but were associated with advanced tumor stage and poorer prognosis. By in situ hybridization and immunohistochemistry, NK-1R mRNA and immunoreactivity were only occasionally weakly present in acinar and ductal cells in the normal pancreas. In contrast, moderate to strong NK-1R mRNA signals and immunoreactivity were present in most cancer cells. By Western blot analysis, NK-1R was increased 26-fold (p < 0.01) in pancreatic cancer samples in comparison to normal controls. NK-1R mRNA was detected in five pancreatic cancer cell lines by real-time quantitative RT-PCR, with the highest levels in CAPAN-1 cells and the lowest in ASPC-1 cells. SP analogs stimulated pancreatic cancer cell growth, depending on the NK-1R expression level, and this effect could be blocked by a selective NK-1R antagonist. These findings illustrate that the NK-1R pathway is activated in human pancreatic cancer and has the potential to contribute to cancer cell growth, thus suggesting the existence of a neuro-cancer cell interaction in vivo.

When to perform a pancreatoduodenectomy in the absence of positive histology? A consensus statement by the International Study Group of Pancreatic Surgery

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.