Johanna A. M. G. Tol

Metal or plastic stents for preoperative biliary drainage in resectable pancreatic cancer

Introduction In pancreatic cancer, preoperative biliary drainage (PBD) increases complications compared with surgery without PBD, demonstrated by a recent randomised controlled trial (RCT). This outcome might be related to the plastic endoprosthesis used. Metal stents may reduce the PBD-related complications risk. Methods A prospective multicentre cohort study was performed including patients with obstructive jaundice due to pancreatic cancer, scheduled to undergo PBD before surgery. This cohort was added to the earlier RCT (ISRCTN31939699). The RCT protocol was adhered to, except PBD was performed with a fully covered self-expandable metal stent (FCSEMS). This FCSEMS cohort was compared with the RCT’s plastic stent cohort. PBD-related complications were the primary outcome. Three-group comparison of overall complications including early surgery patients was performed. Results 53 patients underwent PBD with FCSEMS compared with 102 patients treated with plastic stents. Patients’ characteristics did not differ. PBD-related complication rates were 24% in the FCSEMS group vs 46% in the plastic stent group (relative risk of plastic stent use 1.9, 95% CI 1.1 to 3.2, p=0.011). Stent-related complications (occlusion and exchange) were 6% vs 31%. Surgical complications did not differ, 40% vs 47%. Overall complication rates for the FCSEMS, plastic stent and early surgery groups were 51% vs 74% vs 39%. Conclusions For PBD in pancreatic cancer, FCSEMS yield a better outcome compared with plastic stents. Although early surgery without PBD remains the treatment of choice, FCSEMS should be preferred over plastic stents whenever PBD is indicated. Trial registration number: Dutch Trial Registry (NTR3142).

Impact of lymph node ratio on survival in patients with pancreatic and periampullary cancer

According to some studies, the number of lymph nodes with metastases in relation to the total number of removed lymph nodes, the lymph node ratio (LNR), is one of the most powerful predictors of survival after resection in patients with pancreatic cancer. However, contradictory results have been reported, and small sample sizes of the cohorts and different definitions of a microscopic positive resection margin (R1) hamper the interpretation of data.

Centralization of Highly Complex Low-Volume Procedures in Upper Gastrointestinal Surgery. A Summary of Systematic Reviews and Meta-Analyses

Centralization of complex upper gastrointestinal (GI) surgery and the effect on postoperative outcomes, especially mortality, has been reported extensively in the literature. In this review the highest level of evidence on the volume outcome relationship is discussed together with other important aspects that can influence postoperative outcomes. Do high-volume centers and surgeons result in better outcomes after surgery for the different upper GI surgical procedures such as esophageal, gastric, liver and pancreatic tumors? Twelve systematic reviews including four meta-analyses described the effect of hospital and/or surgeon volume on mortality. The majority of reviews (>90%) showed a lower mortality in high-volume hospitals. This correlation was also reported when analyzing the different GI procedures separately for esophageal, gastric, hepatic and pancreatic tumors. The volume discussion has limitations and therefore the relationship between hospital structure and process of care in hospitals and the outcome of surgery has also been acknowledged. Besides surgeon expertise and skills, high-intensity intensive care units, 24/7 availability of interventional radiology, effective prevention and managing of complications and adequate patient selection will influence postoperative outcomes. These forms of hospital structures and process of care might even play a more important role in surgical outcomes.

Establishment of patient-derived xenograft models and cell lines for malignancies of the upper gastrointestinal tract

BackgroundThe upper gastrointestinal tract is home to some of most notorious cancers like esophagogastric and pancreatic cancer. Several factors contribute to the lethality of these tumors, but one that stands out for both tumor types is the strong inter- as well as intratumor heterogeneity. Unfortunately, genetic tumor models do not match this heterogeneity, and for esophageal cancer no adequate genetic models exist. To allow for an improved understanding of these diseases, tissue banks with sufficient amount of samples to cover the extent of diversity of human cancers are required. Additionally, xenograft models that faithfully mimic and span the breadth of human disease are essential to perform meaningful functional experiments.MethodsWe describe here the establishment of a tissue biobank, patient derived xenografts (PDXs) and cell line models of esophagogastric and pancreatic cancer patients. Biopsy material was grafted into immunocompromised mice and PDXs were used to establish primary cell cultures to perform functional studies. Expression of Hedgehog ligands in patient tumor and matching PDX was assessed by immunohistochemical staining, and quantitative real-time PCR as well as flow cytometry was used for cultured cells. Cocultures with Hedgehog reporter cells were performed to study paracrine signaling potency. Furthermore, SHH expression was modulated in primary cultures using lentiviral mediated knockdown.ResultsWe have established a panel of 29 PDXs from esophagogastric and pancreatic cancers, and demonstrate that these PDXs mirror several of the (immuno)histological and biochemical characteristics of the original tumors. Derived cell lines can be genetically manipulated and used to further study tumor biology and signaling capacity. In addition, we demonstrate an active (paracrine) Hedgehog signaling mode by both tumor types, the magnitude of which has not been compared directly in previous studies.ConclusionsOur established PDXs and their matching primary cell lines retain important characteristics seen in the original tumors, and this should enable future studies to address the responses of these tumors to different treatment modalities, but also help in gaining mechanistic insight in how some tumors respond to certain regimens and others do not.

The quandary of preresection biliary drainage for pancreatic cancer.

Abstract Surgery in patients with obstructive jaundice caused by a tumor in the pancreatic head area is associated with a higher risk of postoperative complications. Preoperative biliary drainage was introduced in an attempt to improve the general condition and reduce morbidity and mortality. Extensive experimental studies have been performed to analyze the beneficial effect of biliary drainage and showed improvement in liver function, nutritional status, and cell-mediated immune function as well as reduction in mortality. However, despite the results seen in the experimental studies, clinical studies reported both beneficial and adverse effects, and most studies advised against routinely performing preoperative biliary drainage. To add clarity to the ongoing controversy, a recent randomized controlled trial was performed and reported more overall complications in patients with jaundice who underwent preoperative biliary drainage followed by surgery compared to those who underwent surgery alone. Many of these complications were stent related. Like most clinical studies, a plastic stent was used to initiate biliary drainage. Patients with jaundice because of a tumor in the pancreatic head area without locoregional irresectability or metastases should be candidates for early surgery. Preoperative biliary drainage should not be performed routinely. However, some selected patients might benefit from preoperative biliary drainage, in cases of severe jaundice, neoadjuvant therapy, or postponed surgery due to logistics. In these cases, the use of metal biliary stents is indicated.

Leakage of the gastroenteric anastomosis after pancreatoduodenectomy.

BACKGROUND Common anastomotic complications after pancreatoduodenectomy (PD) are leakage from the pancreaticojejunostomy or hepaticojejunostomy. Leakage from the gastroenteric anastomosis has rarely been described. We evaluated the incidence of gastroenteric leakage after PD and described its presentation, treatment, and outcome. METHODS Between 1992 and 2012, a consecutive series of 1,036 patients underwent PD in the Academic Medical Center. By use of a prospective database and medical records, we identified patients with gastroenteric leakage. Clinicopathologic data were compared with patients without gastroenteric leakage, and presentation, radiologic findings, treatment, and outcome of gastroenteric leaks were analyzed. RESULTS Twelve patients (1.2%) had gastroenteric leakage. Patients with gastroenteric leaks had undergone longer operative procedures, had more pancreatic fistulas and other complications, and had a significantly longer hospital stay. Median postoperative day of diagnosis was 8 (range, 2-23). Clinical signs included tender abdomen and high drain output suspicious of gastric content. Common radiologic findings were pneumoperitoneum and intra-abdominal fluid. Seven patients (58%) were treated operatively, 4 (33%) by percutaneous drainage, and 1 (8%) underwent no specific treatment duo to his poor clinical condition. This patient died in hospital, resulting in a hospital mortality of 8%. CONCLUSION Gastroenteric leakage after PD is rare. Clinical presentation is not specific, unlike leakage from other sites. Drain output suspicious of gastric content may help to differentiate from pancreatic or hepatic anastomotic leakage. It may be associated with a longer duration of operation and concomitant pancreatic fistula. A good outcome depends on prompt diagnosis and is mostly achieved by operative intervention.

Management of Severe Pancreatic Fistula After Pancreatoduodenectomy

Importance Postoperative pancreatic fistula is a potentially life-threatening complication after pancreatoduodenectomy. Evidence for best management is lacking. Objective To evaluate the clinical outcome of patients undergoing catheter drainage compared with relaparotomy as primary treatment for pancreatic fistula after pancreatoduodenectomy. Design, Setting, and Participants A multicenter, retrospective, propensity-matched cohort study was conducted in 9 centers of the Dutch Pancreatic Cancer Group from January 1, 2005, to September 30, 2013. From a cohort of 2196 consecutive patients who underwent pancreatoduodenectomy, 309 patients with severe pancreatic fistula were included. Propensity score matching (based on sex, age, comorbidity, disease severity, and previous reinterventions) was used to minimize selection bias. Data analysis was performed from January to July 2016. Exposures First intervention for pancreatic fistula: catheter drainage or relaparotomy. Main Outcomes and Measures Primary end point was in-hospital mortality; secondary end points included new-onset organ failure. Results Of the 309 patients included in the analysis, 209 (67.6%) were men, and mean (SD) age was 64.6 (10.1) years. Overall in-hospital mortality was 17.8% (55 patients): 227 patients (73.5%) underwent primary catheter drainage and 82 patients (26.5%) underwent primary relaparotomy. Primary catheter drainage was successful (ie, survival without relaparotomy) in 175 patients (77.1%). With propensity score matching, 64 patients undergoing primary relaparotomy were matched to 64 patients undergoing primary catheter drainage. Mortality was lower after catheter drainage (14.1% vs 35.9%; P = .007; risk ratio, 0.39; 95% CI, 0.20-0.76). The rate of new-onset single-organ failure (4.7% vs 20.3%; P = .007; risk ratio, 0.15; 95% CI, 0.03-0.60) and new-onset multiple-organ failure (15.6% vs 39.1%; P = .008; risk ratio, 0.40; 95% CI, 0.20-0.77) were also lower after primary catheter drainage. Conclusions and Relevance In this propensity-matched cohort, catheter drainage as first intervention for severe pancreatic fistula after pancreatoduodenectomy was associated with a better clinical outcome, including lower mortality, compared with primary relaparotomy.

Recent Advances in Pancreatic Cancer Surgery of Relevance to the Practicing Pathologist

Recent advances in pancreatic surgery have the potential to improve outcomes for patients with pancreatic cancer. We address 3 new, trending topics in pancreatic surgery that are of relevance to the pathologist. First, increasing awareness of the prognostic impact of intraoperatively detected extraregional and regional lymph node metastases and the international consensus definition on lymph node sampling and reporting. Second, neoadjuvant chemotherapy, which is capable of changing 10% to 20% of initially unresectable, to resectable disease. Third, in patients who remain unresectable following neoadjuvant chemotherapy, local ablative therapies may change indications for treatment and improve outcomes.