The Value of Textbook Outcome in Benchmarking Pancreatoduodenectomy for Nonfunctioning Pancreatic Neuroendocrine Tumors.

BACKGROUND: Textbook outcome (TO) is a composite variable that can define the quality of pancreatic surgery. The aim of this study is to evaluate TO after pancreatoduodenectomy (PD) for nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs). PATIENTS AND METHODS: All patients who underwent PD for NF-PanNETs (2007-2016) in different centers were included in this retrospective study. TO was defined as the absence of severe postoperative complications and mortality, length of hospital stay ≤ 19 days, R0 resection, and at least 12 lymph nodes harvested. RESULTS: Overall, 477 patients were included. The TO rate was 32%. Tumor size [odds ratio (OR) 1.696; p = 0.013], a minimally invasive approach (OR 12.896; p = 0.001), and surgical volume (OR 2.062; p = 0.023) were independent predictors of TO. The annual frequency of PDs increased over time as well as the overall rate of TO. At a median follow-up of 44 months, patients who achieved TO had similar disease-free (p = 0.487) and overall survival (p = 0.433) rates compared with patients who did not achieve TO. TO rate in patients with NF-PanNET > 2 cm was 35% versus 27% in patients with NF-PanNET ≤ 2 cm (p = 0.044). Considering only NF-PanNETs > 2 cm, patients with TO and those without TO had comparable 5-year overall survival rates (p = 0.766) CONCLUSIONS: TO is achieved in one-third of patients after PD for NF-PanNETs and is not associated with a benefit in terms of long-term survival.

Meta-analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer.

BACKGROUND: Studies comparing upfront surgery with neoadjuvant treatment in pancreatic cancer may report only patients who underwent resection and so survival will be skewed. The aim of this study was to report survival by intention to treat in a comparison of upfront surgery versus neoadjuvant treatment in resectable or borderline resectable pancreatic cancer. METHODS: MEDLINE, Embase and the Cochrane Library were searched for studies reporting median overall survival by intention to treat in patients with resectable or borderline resectable pancreatic cancer treated with or without neoadjuvant treatment. Secondary outcomes included overall and R0 resection rate, pathological lymph node rate, reasons for unresectability and toxicity of neoadjuvant treatment. RESULTS: In total, 38 studies were included with 3484 patients, of whom 1738 (49·9 per cent) had neoadjuvant treatment. The weighted median overall survival by intention to treat was 18·8 months for neoadjuvant treatment and 14·8 months for upfront surgery; the difference was larger among patients whose tumours were resected (26·1 versus 15·0 months respectively). The overall resection rate was lower with neoadjuvant treatment than with upfront surgery (66·0 versus 81·3 per cent; P < 0·001), but the R0 rate was higher (86·8 (95 per cent c.i. 84·6 to 88·7) versus 66·9 (64·2 to 69·6) per cent; P < 0·001). Reported by intention to treat, the R0 rates were 58·0 and 54·9 per cent respectively (P = 0·088). The pathological lymph node rate was 43·8 per cent after neoadjuvant therapy and 64·8 per cent in the upfront surgery group (P < 0·001). Toxicity of at least grade III was reported in up to 64 per cent of the patients. CONCLUSION: Neoadjuvant treatment appears to improve overall survival by intention to treat, despite lower overall resection rates for resectable or borderline resectable pancreatic cancer. PROSPERO registration number: CRD42016049374.

Nationwide comprehensive gastro-intestinal cancer cohorts: the 3P initiative.

BACKGROUND: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients. MATERIAL AND METHODS: All patients aged ≥18 years with pancreatic, esophageal/gastric or colorectal cancer are eligible. Patients provide informed consent for: (1) reuse of clinical data; (2) biobanking of primary tumor tissue; (3) collection of blood samples; (4) to be informed about relevant newly identified genomic aberrations; (5) collection of longitudinal PROs; and (6) to receive information on new interventional studies and possible participation in cohort multiple randomized controlled trials (cmRCT) in the future. RESULTS: In 2015, clinical data of 21,758 newly diagnosed patients were collected in the Netherlands Cancer Registry. Additional clinical data on the surgical procedures were registered in surgical audits for 13,845 patients. Within the first two years, tumor tissue and blood samples were obtained from 1507 patients; during this period, 1180 patients were included in the PRO registry. Response rate for PROs was 90%. The consent rate to receive information on new interventional studies and possible participation in cmRCTs in the future was >85%. The number of hospitals participating in the cohorts is steadily increasing. CONCLUSION: A comprehensive nationwide multidisciplinary gastrointestinal cancer cohort is feasible and surpasses the limitations of classical study designs. With this initiative, novel and innovative studies can be performed in an efficient, safe, and comprehensive setting.

Nationwide outcomes in patients undergoing surgical exploration without resection for pancreatic cancer.

BACKGROUND: Despite improvements in diagnostic imaging and staging, unresectable pancreatic cancer is still encountered during surgical exploration with curative intent. This nationwide study investigated outcomes in patients with unresectable pancreatic cancer found during surgical exploration. METHODS: All patients diagnosed with primary pancreatic (adeno)carcinoma (2009-2013) in the Netherlands Cancer Registry were included. Predictors of unresectability, 30-day mortality and poor survival were evaluated using logistic and Cox proportional hazards regression analysis. RESULTS: There were 10 595 patients with pancreatic cancer during the study interval. The proportion of patients undergoing surgical exploration increased from 19·9 to 27·0 per cent (P < 0·001). Among 2356 patients who underwent surgical exploration, the proportion of patients with tumour resection increased from 61·6 per cent in 2009 to 71·3 per cent in 2013 (P < 0·001), whereas the contribution of M1 disease (18·5 per cent overall) remained stable. Patients who had exploration only had an increased 30-day mortality rate compared with those who underwent tumour resection (7·8 versus 3·8 per cent; P < 0·001). In the non-resected group, among those with M0 (383 patients) and M1 (435) disease at surgical exploration, the 30-day mortality rate was 4·7 and 10·6 per cent (P = 0·002), median survival was 7·2 and 4·4 months (P < 0·001), and 1-year survival rates were 28·0 and 12·9 per cent, respectively. Among other factors, low hospital volume (0-20 resections per year) was an independent predictor for not undergoing tumour resection, but also for 30-day mortality and poor survival among patients without tumour resection. CONCLUSION: Exploration and resection rates increased, but one-third of patients who had surgical exploration for pancreatic cancer did not undergo resection. Non-resectional surgery doubled the 30-day mortality rate compared with that in patients undergoing tumour resection.

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).

The influence of somatostatin receptor scintigraphy during preoperative staging of non-functioning pancreatic neuroendocrine tumours.

AIM: To determine whether somatostatin receptor scintigraphy (SRS) influences the preoperative staging and clinical management of non-functioning pancreatic neuroendocrine tumours (NF-pNETs). MATERIALS AND METHODS: All SRS examinations performed between 2002-2013 were selected. Patients with NF-pNET were included if both computed tomography (CT) and SRS was performed during preoperative staging. The diagnostic accuracy of CT and SRS for detecting NF-pNET metastases was analysed. Altered TNM classification and changed clinical management were calculated. Changed management was defined as a change from surgical resection into systemic treatment or vice versa. NF-pNETs were defined as tumours without clinical symptoms of hormonal hypersecretion. RESULTS: Overall, 62 patients with NF-pNET were included with a mean age of 57 years (SD: 12.4)(2). In 28 patients (45%), CT and SRS were correct and in agreement in the detection of primary tumour/metastases. In 34 patients (55%), one of the techniques was incorrect and therefore, there was no agreement. SRS altered the TNM classification in 14 patients (23%) and clinical management in nine patients (15%). In patients without metastases on CT, SRS detected lymph node metastases in one patient. The sensitivity to detect the primary tumour with CT was 95% and with SRS was 73%. In detecting metastases, the sensitivity and specificity were both 85% for CT versus 80% and 90% for SRS. CONCLUSION: Overall, CT and SRS were in agreement in the detection of NF-pNET. In NF-pNET without suspicious metastatic lesions on CT, SRS has limited value. SRS may be indicated to confirm lesions suspicious for neuroendocrine tumours metastases.

Preoperative chemoradiotherapy for esophageal or junctional cancer.

BACKGROUND: The role of neoadjuvant chemoradiotherapy in the treatment of patients with esophageal or esophagogastric-junction cancer is not well established. We compared chemoradiotherapy followed by surgery with surgery alone in this patient population. METHODS: We randomly assigned patients with resectable tumors to receive surgery alone or weekly administration of carboplatin (doses titrated to achieve an area under the curve of 2 mg per milliliter per minute) and paclitaxel (50 mg per square meter of body-surface area) for 5 weeks and concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week), followed by surgery. RESULTS: From March 2004 through December 2008, we enrolled 368 patients, 366 of whom were included in the analysis: 275 (75%) had adenocarcinoma, 84 (23%) had squamous-cell carcinoma, and 7 (2%) had large-cell undifferentiated carcinoma. Of the 366 patients, 178 were randomly assigned to chemoradiotherapy followed by surgery, and 188 to surgery alone. The most common major hematologic toxic effects in the chemoradiotherapy-surgery group were leukopenia (6%) and neutropenia (2%); the most common major nonhematologic toxic effects were anorexia (5%) and fatigue (3%). Complete resection with no tumor within 1 mm of the resection margins (R0) was achieved in 92% of patients in the chemoradiotherapy-surgery group versus 69% in the surgery group (P<0.001). A pathological complete response was achieved in 47 of 161 patients (29%) who underwent resection after chemoradiotherapy. Postoperative complications were similar in the two treatment groups, and in-hospital mortality was 4% in both. Median overall survival was 49.4 months in the chemoradiotherapy-surgery group versus 24.0 months in the surgery group. Overall survival was significantly better in the chemoradiotherapy-surgery group (hazard ratio, 0.657; 95% confidence interval, 0.495 to 0.871; P=0.003). CONCLUSIONS: Preoperative chemoradiotherapy improved survival among patients with potentially curable esophageal or esophagogastric-junction cancer. The regimen was associated with acceptable adverse-event rates. (Funded by the Dutch Cancer Foundation [KWF Kankerbestrijding]; Netherlands Trial Register number, NTR487.).

Survival after resection of perihilar cholangiocarcinoma-development and external validation of a prognostic nomogram.

BACKGROUND: The objective of this study was to derive and validate a prognostic nomogram to predict disease-specific survival (DSS) after a curative intent resection of perihilar cholangiocarcinoma (PHC). PATIENTS AND METHODS: A nomogram was developed from 173 patients treated at Memorial Sloan Kettering Cancer Center (MSKCC), New York, USA. The nomogram was externally validated in 133 patients treated at the Academic Medical Center (AMC), Amsterdam, The Netherlands. Prognostic accuracy was assessed with concordance estimates and calibration, and compared with the American Joint Committee on Cancer (AJCC) staging system. The nomogram will be available as web-based calculator at mskcc.org/nomograms. RESULTS: For all 306 patients, the median overall survival (OS) was 40 months and the median DSS 41 months. Median follow-up for patients alive at last follow-up was 48 months. Lymph node involvement, resection margin status, and tumor differentiation were independent prognostic factors in the derivation cohort (MSKCC). A nomogram with these prognostic factors had a concordance index of 0.73 compared with 0.66 for the AJCC staging system. In the validation cohort (AMC), the concordance index was 0.72, compared with 0.60 for the AJCC staging system. Calibration was good in the derivation cohort; in the validation cohort patients had a better median DSS than predicted by the model. CONCLUSIONS: The proposed nomogram to predict DSS after curative intent resection of PHC had a better prognostic accuracy than the AJCC staging system. Calibration was suboptimal because DSS differed between the two institutions. The nomogram can inform patients and physicians, guide shared decision making for adjuvant therapy, and stratify patients in future randomized, controlled trials.

Gastric emptying and quality of life after pancreatoduodenectomy with retrocolic or antecolic gastroenteric anastomosis.

BACKGROUND: Delayed gastric emptying (DGE) is a major problem after pancreatoduodenectomy (PD). A recent multicentre randomized trial reported no difference in gastric emptying rates between retrocolic and antecolic reconstruction routes. The present study looked at quality of life with these two approaches and the correlation with gastric emptying. METHODS: This was a substudy of patients completing a panel of quality-of-life questionnaires within a randomized trial comparing retrocolic and antecolic gastroenteric reconstruction after PD. Gastric emptying was assessed by scintigraphy 1 week after surgery. Quality of life was measured with the EuroQoL - 5D questionnaire (EQ-5D), the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30) with its pancreatic cancer module (PAN26), and the Gastrointestinal Quality of Life Index (GIQLI). RESULTS: There were 38 patients in the retrocolic and 35 in the antecolic group. Baseline characteristics and clinical outcomes were similar in the two groups. Median time to half-emptying of stomach content after surgery was 145 and 64 min in the retrocolic and antecolic group respectively (P = 0.189). Median percentages of residual activity after 2 h were 64 and 28 per cent respectively (P = 0.213). Quality of life did not differ at any time point between the groups. At 2 weeks after surgery, patients with DGE had significantly worse outcomes on two EQ-5D domains, ten QLQ-C30/PAN26 subscales, and two GIQLI subscales and total score. Effect sizes were moderate to large. CONCLUSION: The route of gastroenteric reconstruction after PD does not influence either gastric emptying at scintigraphy or quality of life. The impact of DGE on quality of life is clinically significant. Registration number NTR1697 (www.trialregister.nl).

Hospital of diagnosis and likelihood of surgical treatment for pancreatic cancer.

BACKGROUND: Surgical resection for pancreatic cancer offers the only chance of cure. Assessment of the resectability of a pancreatic tumour is therefore of great importance. The aim of the study was to investigate whether centre of diagnosis influences the likelihood of surgery and whether this affects long-term survival. METHODS: Patients diagnosed with non-metastasized pancreatic cancer (M0) between 2005 and 2013 in the Netherlands were selected from the Netherlands Cancer Registry. Hospitals were classified as a pancreatic centre (at least 20 resections/year) or a non-pancreatic centre (fewer than 20 resections/year). The relationship between centre of diagnosis and likelihood of surgery was analysed by multivariable logistic regression. Influence of centre on overall survival was assessed by means of multivariable Cox regression analysis. RESULTS: Some 8141 patients were diagnosed with non-metastasized pancreatic cancer, of whom 3123 (38·4 per cent) underwent surgery. Of the 2712 patients diagnosed in one of 19 pancreatic centres, 52·4 per cent had exploratory laparotomy compared with 31·4 per cent of 5429 patients diagnosed in one of 74 non-pancreatic centres (P < 0·001). A pancreatectomy was performed in 42·8 and 24·6 per cent of the patients respectively (P < 0·001). Multivariable analysis revealed that patients diagnosed in a pancreatic centre had a higher chance of undergoing surgery (odds ratio 2·21, 95 per cent c.i. 1·98 to 2·47). Centre of diagnosis was not associated with improved long-term survival (hazard ratio 0·95, 95 per cent c.i. 0·91 to 1·00). CONCLUSION: Patients with non-metastasized pancreatic cancer had a greater likelihood of having surgical treatment when the diagnosis was established in a pancreatic centre.

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

BACKGROUND: 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. METHODS: The predictive value of LNR for 3-year survival was assessed using a Cox proportional hazards model. From 1992 to 2012, all patients with pancreatic and periampullary cancer operated on with pancreatoduodenectomy were selected from a database. Clinicopathological characteristics were analysed. Microscopic positive resection margin was defined as the microscopic presence of tumour cells within 1 mm of the margins. A nomogram was created. RESULTS: Some 760 patients were included. Predictive factors for death in 350 patients with pancreatic ductal adenocarcinoma included in the nomogram were: R1 resection (hazard ratio (HR) 1·55, 95 per cent c.i. 1·07 to 2·25), poor tumour differentiation (HR 2·78, 1·40 to 5·52), LNR above 0·18 (HR 1·75, 1·13 to 2·70) and no adjuvant therapy (HR 1·54, 1·01 to 2·34). The C statistic was 0·658 (0·632 to 0·698), and calibration was good (Hosmer-Lemeshow χ(2) = 5·67, P =0·773). LNR and poor tumour differentiation (HR 4·51 and 3·30 respectively) were also predictive in patients with distal common bile duct (CBD) cancer. LNR, R1 resection and jaundice were predictors of death in patients with ampullary cancer (HR 7·82, 2·68 and 1·93 respectively). CONCLUSION: LNR is a common predictor of poor survival in pancreatic, distal CBD and ampullary cancer.

Systematic review of innovative ablative therapies for the treatment of locally advanced pancreatic cancer.

BACKGROUND: Locally advanced pancreatic cancer (LAPC) is associated with a very poor prognosis. Current palliative (radio)chemotherapy provides only a marginal survival benefit of 2-3 months. Several innovative local ablative therapies have been explored as new treatment options. This systematic review aims to provide an overview of the clinical outcomes of these ablative therapies. METHODS: A systematic search in PubMed, Embase and the Cochrane Library was performed to identify clinical studies, published before 1 June 2014, involving ablative therapies in LAPC. Outcomes of interest were safety, survival, quality of life and pain. RESULTS: After screening 1037 articles, 38 clinical studies involving 1164 patients with LAPC, treated with ablative therapies, were included. These studies concerned radiofrequency ablation (RFA) (7 studies), irreversible electroporation (IRE) (4), stereotactic body radiation therapy (SBRT) (16), high-intensity focused ultrasound (HIFU) (5), iodine-125 (2), iodine-125-cryosurgery (2), photodynamic therapy (1) and microwave ablation (1). All strategies appeared to be feasible and safe. Outcomes for postoperative, procedure-related morbidity and mortality were reported only for RFA (4-22 and 0-11 per cent respectively), IRE (9-15 and 0-4 per cent) and SBRT (0-25 and 0 per cent). Median survival of up to 25·6, 20·2, 24·0 and 12·6 months was reported for RFA, IRE, SBRT and HIFU respectively. Pain relief was demonstrated for RFA, IRE, SBRT and HIFU. Quality-of-life outcomes were reported only for SBRT, and showed promising results. CONCLUSION: Ablative therapies in patients with LAPC appear to be feasible and safe.

Is current perioperative practice in hepatic surgery based on enhanced recovery after surgery (ERAS) principles?

BACKGROUND: The worldwide introduction of multimodal enhanced recovery programs has also changed perioperative care in patients who undergo liver resection. This study was performed to assess current perioperative practice in liver surgery in 11 European HPB centers and compare it to enhanced recovery after surgery (ERAS) principles. METHODS: In each unit, 15 consecutive patients (N = 165) who underwent hepatectomy between 2010 and 2012 were retrospectively analyzed. Compliance was classified as "full," "partial," or "poor" whenever ≥ 80, ≥ 50, or <50 % of the 22 ERAS protocol core items were met. The primary study end point was overall compliance with the ERAS core program per unit and per perioperative phase. RESULTS: Most patients were operated on for malignancy (91 %) and 56 % were minor hepatectomies. The median number of implemented ERAS core items was 9 (range = 7-12) across all centers. Compliance was partial in the preoperative (median 2 of 3 items, range = 1-3) and perioperative phases (median 5 of 10 items, range: 4-7). Median postoperative compliance was poor (median 2 of 9 items, range = 0-4). A statistically significant difference was observed between median length of stay and median time to recovery (7 vs. 5 days, P < 0.001). CONCLUSION: Perioperative care among centers that perform liver resections varied substantially. In current HPB surgical practice, some elements of the ERAS program, e.g., preoperative counselling and minimal fasting, have already been implemented. Elements in the perioperative phase (avoidance of drains and nasogastric tube) and postoperative phase (early resumption of oral intake, early mobilization, and use of recovery criteria) should be further optimized.

Partial liver resection because of bile duct injury.

AIM: To analyze the outcome of partial liver resection (PHx) after bile duct injury (BDI) in patients after multimodality treatment. METHODS: Between 1990 and 2012, 800 BDI patients were referred to our tertiary center. Patient characteristics and long-term outcomes were described. RESULTS: PHx was performed in 11 patients (1.4%), mean age 48.3 years (range 29.3-83.5 years), mainly because of complex injury [Amsterdam classification type D (n = 10, 91%), Strasberg type E (n = 7, 64%) and Bismuth type IV (n = 8, 73%)]. In 7 patients (64%), concomitant vasculobiliary injury had occurred in the right hepatic artery (n = 3), proper hepatic artery (n = 1), portal vein (PV; n = 2) and the right hepatic artery and PV simultaneously (n = 1). Early PHx was performed in 2 patients and delayed resection in 9 patients after a median of 57.8 months (range 3.9-183.4 months). The in-hospital mortality was 18% (n = 2) and long-term mortality 9% (n = 1). There were no significant differences in postoperative complications between early and late resection. CONCLUSIONS: Indications for PHx after BDI in patients referred to a tertiary center are relatively low (1.4%) and generally apply to vasculobiliary injury. The implications for treatment are important, so it is worthwhile to classify vascular injuries in the management of BDI.

Neoadjuvant chemoradiotherapy followed by esophagectomy does not increase morbidity in patients over 70.

Esophagectomy in elderly esophageal carcinoma patients is correlated with a high morbidity and even mortality. Studies on neoadjuvant chemoradiotherapy (NT) in elderly patients are scarce. The aim of this study was to evaluate the effect of advanced age in combination with NT in esophageal carcinoma patients who underwent an esophagectomy. Patients who underwent NT prior to esophagectomy between 1993 and 2010 were divided into three groups: <70, 70-74, and ≥75 years. Toxicity of NT and postoperative morbidity were compared between groups. Primary endpoints were toxicity, complication rate, and survival. Two hundred thirteen patients underwent NT during the study period, 26 were aged 70-74 years, and 17 were ≥70 years. Toxicity of NT was comparable for younger and elderly patients (46% vs. 54% vs. 47%, P = 0.263). Overall complications occurred in 62% of younger patients versus 73% and 71% among patients aged 70-74 years and ≥75 years, respectively (P = 0.836). Cardiac complications occurred in 14% of younger patients versus 27% and 41% of elderly patients (P = 0.021). Three-year survival rates were 59% versus 44% versus 31% among patients aged <70, 70-74, and ≥75 years, respectively (P = 0.237). Higher age (odds ratio 1.750, P < 0.001) was an independent risk factor for development of cardiac complications. Toxicity of NT and postoperative complications are comparable for patients aged <70, 70-74, and ≥75 years, with the exception of cardiac complications. Therefore, we consider NT followed by esophagectomy in elderly patients a safe treatment modality in our center.

Survival analysis and prognostic nomogram for patients undergoing resection of extrahepatic cholangiocarcinoma.

BACKGROUND: Tumor location of extrahepatic cholangiocarcinoma (CCA) might influence survival after resection. METHODS: A consecutive series of 175 patients who had undergone a potentially curative resection of extrahepatic CCA was analyzed. We calculated concordance indices of different constructed prognostic models for survival including TNM (tumour-node-metastasis) staging and developed a nomogram of the most sensitive model. RESULTS: Overall cancer-specific survival rates were 83%, 58%, and 26% at 1, 2, and 5 years, respectively. Cancer-specific survival according to location was 42% for proximal, 23% for mid, and 19% for distal CCA after 5 years. Tumor location was not an independent significant predictor (P = 0.06). A prognostic model using all potential prognostic variables predicted survival better compared with TNM staging (concordance index 0.65 versus 0.63). A reduced model containing only lymph node status, microscopically residual tumor status, and tumor differentiation grade, also outperformed TNM staging (concordance index 0.66). CONCLUSIONS: Tumor location of extrahepatic CCA does not independently predict cancer-specific survival after resection. We developed a nomogram, based on a prognostic model with lymph node status, microscopically residual tumor status of resection margins, and tumor differentiation grade, that predicted survival better than TNM staging.

A high body mass index in esophageal cancer patients does not influence postoperative outcome or long-term survival.

BACKGROUND: The body mass index (BMI) in the general population has increased over the past decades. A high BMI is a known risk factor for the development of esophageal adenocarcinoma. Several studies on the influence of a high BMI on the postoperative course and survival after esophagectomy have shown contradictory results. The aim of the present study was to determine the influence of a high BMI on postoperative complications and survival among a large cohort of esophageal cancer patients. METHODS: Patients who underwent an esophagectomy between 1993 and 2010 were divided into three groups according to their BMI: normal weight (<25 kg/m(2)), overweight (25-30 kg/m(2)) or obese (≥ 30 kg/m(2)). Severity of complications was scored according to the Dindo classification, which was divided into three categories: no complications, minor to moderate complications, and severe complications. Long-term survival was determined according to the Kaplan-Meier method. RESULTS: A total of 736 esophagectomy patients were divided into three groups: normal weight (n = 352), overweight (n = 308), and obese (n = 72). Complications rates were similar for all groups (65-72%, P = 0.241). The incidence of anastomotic leakage was higher among obese patients compared to the other groups (20% vs. 10-12% respectively, P = 0.019), but there was no significant difference between the three groups regarding the severity of complications according to the Dindo classification (P = 0.660) or in 5-year survival rates (P = 0.517). CONCLUSIONS: A high BMI is not associated with an increased incidence or severity of complications after esophagectomy; however, anastomotic leakage occurred more frequently in obese patients. Five-year survival rates were not influenced by the preoperative BMI. A high BMI is therefore ought not be an exclusion criterion for esophagectomy.

Impact of nationwide centralization of pancreaticoduodenectomy on hospital mortality.

BACKGROUND: The impact of nationwide centralization of pancreaticoduodenectomy (PD) on mortality is largely unknown. The aim of this study was to analyse changes in hospital volumes and in-hospital mortality after PD in the Netherlands between 2004 and 2009. METHODS: Nationwide data on International Classification of Diseases, ninth revision (ICD-9) code 5-526 (PD, including Whipple), patient age, sex and mortality were retrieved from the independent nationwide KiwaPrismant registry. Based on established cut-off points of annually performed PDs, hospitals were categorized as very low (fewer than 5), low (5-10), medium (11-19) or high (at least 20) volume. A subgroup analysis based on a cut-off age of 70 years was also performed. RESULTS: Some 2155 PDs were included. The number of hospitals performing PD decreased from 48 in 2004 to 30 in 2009 (P = 0·011). In these specific years, the proportion of patients undergoing PD in a medium- or high-volume centre increased from 52·9 to 91·2 per cent (P < 0·001). Nationwide mortality rates after PD decreased from 9·8 to 5·1 per cent (P = 0·044). The mortality rate during the 6-year period was 14·7, 9·8, 6·3 and 3·3 per cent in very low-, low-, medium- and high-volume hospitals respectively (P < 0·001). The difference in mortality between medium- and high-volume centres was statistically significant (P = 0·004). The volume-outcome relationship was not influenced by age (P = 0·467). The mortality rate after PD in patients aged at least 70 years was 10·4 per cent compared with 4·4 per cent in younger patients (P < 0·001). CONCLUSION: With nationwide centralization of PD, the in-hospital mortality rate after this procedure decreased. Further centralization of PD is likely to decrease mortality further, especially in the elderly.