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Contains fulltext : 291891.pdf (Publisher’s version ) (Closed access) BACKGROUND: The International Study Group of Pancreatic Surgery 4-tier (ie, A-D) risk classification for postoperative pancreatic fistula grade B/C is based on pancreatic texture and pancreatic duct size: A (not-soft texture and pancreatic duct >3 mm), B (not-soft texture and pancreatic duct ≤3 mm), C (soft texture and pancreatic duct >3 mm), and D (soft texture and pancreatic duct ≤3 mm). This study aimed to validate the International Study Group of Pancreatic Surgery risk classification for postoperative pancreatic fistula after pancreatoduodenectomy. METHODS: Consecutive patients after pancreatoduodenectomy for all indications (2014-2021) were included from the nationwide, mandatory Dutch Pancreatic Cancer Audit. The rate of postoperative pancreatic fistula grade B/C (according to the International Study Group of Pancreatic Surgery 2016 definition) was calculated per risk category. Model performance was assessed using the area under the receiver operating curve (discrimination) and calibration plots. RESULTS: Overall, 3,900 patients were included in risk categories: A (n = 1,046), B (n = 498), C (n = 963), and D (n = 1,393) with corresponding postoperative pancreatic fistula grade B/C rates of 3.8%, 12.2%, 15.6%, and 29.6%. Per category, the in-hospital mortality rates were 1.3%, 3.4%, 2.9%, and 4.1%, P = .001. There was no difference in the rate of postoperative pancreatic fistula between risk categories B and C (12.2% vs 15.6%, P = .101). When simplifying the classification system to a 3-tier classification system (based on 0, 1, and 2 risk factors), the discrimination was not significantly different (area under the receiver operating curve 0.697 vs area under the receiver operating curve 0.701, P = .077). CONCLUSION: This validation of the 4-tier International Study Group of Pancreatic Surgery risk classification for postoperative pancreatic fistula after pancreatoduodenectomy confirmed its predictive value. However, as the 2 middle risk categories provide no added predictive value, a simplified 3-tier classification with comparable predictive value is proposed and should be validated in future prospective studies.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma, the main cellular constituents of which are cancer-associated fibroblasts (CAFs). Stroma-targeting agents have been proposed to improve the poor outcome of current treatments. However, clinical trials using these agents showed disappointing results. Heterogeneity in the PDAC CAF population was recently delineated demonstrating that both tumor-promoting and tumor-suppressive activities co-exist in the stroma. Here, we aimed to identify biomarkers for the CAF population that contribute to a favorable outcome. RNA-sequencing reads from patient-derived xenografts (PDXs) were mapped to the human and mouse genome to allocate the expression of genes to the tumor or stroma. Survival meta-analysis for stromal genes was performed and applied to human protein atlas data to identify circulating biomarkers. The candidate protein was perturbed in co-cultures and assessed in existing and novel single-cell gene expression analysis from control, pancreatitis, pancreatitis-recovered and PDAC mouse models. Serum levels of the candidate biomarker were measured in two independent cohorts totaling 148 PDAC patients and related them to overall survival. Osteoglycin (OGN) was identified as a candidate serum prognostic marker. Single-cell analysis indicated that Ogn is derived from a subgroup of inflammatory CAFs. Ogn-expressing fibroblasts are distinct from resident healthy pancreatic stellate cells and arise during pancreatitis. Serum OGN levels were prognostic for favorable overall survival in two independent PDAC cohorts (HR = 0.47, P = .042 and HR = 0.53, P = .006). Altogether, we conclude that high circulating OGN levels inform on a previously unrecognized subgroup of CAFs and predict favorable outcomes in resectable PDAC.

Background and Aims: In high-risk individuals (HRIs), we aimed to assess the cumulative incidence of intraductal papillary mucinous neoplasms (IPMNs) and compare IPMN growth, neoplastic progression rate, and the value of growth as predictor for neoplastic progression to these in sporadic IPMNs. Methods: We performed annual surveillance of Dutch HRIs, involving carriers of germline pathogenic variants (PVs) and PV-negative familial pancreatic cancer kindreds. HRIs with IPMNs were compared with Italian individuals without familial risk under surveillance for sporadic IPMNs. Results: A total of 457 HRIs were followed for 48 (range 2–172) months; the estimated cumulative IPMN incidence was 46% (95% confidence interval, 28%–64%). In comparison with 442 control individuals, IPMNs in HRIs were more likely to grow ≥2.5 mm/y (31% vs 7%; P < .001) and develop worrisome features (32% vs 19%; P = .010). PV carriers with IPMNs more often displayed neoplastic progression (n = 3 [11%] vs n = 6 [1%]; P = .011), while familial pancreatic cancer kindreds did not (n = 0 [0%]; P = 1.000). The malignancy risk in a PV carrier with an IPMN was 23% for growth rates ≥2.5 mm/y (n = 13), 30% for ≥5 mm/y (n = 10), and 60% for ≥10 mm/y (n = 5). Conclusions: The cumulative incidence of IPMNs in HRIs is higher than previously reported in the general population. Compared with sporadic IPMNs, they have an increased growth rate. PV carriers with IPMNs are suggested to be at a higher malignancy risk. Intensive follow-up should be considered for PV carriers with an IPMN growing ≥2.5 mm/y, and surgical resection for those growing ≥5 mm/y.

OBJECTIVE: To describe outcome after pancreatic surgery in the first six years of a mandatory nationwide audit. BACKGROUND: Within the Dutch Pancreatic Cancer Group, efforts have been made to improve outcome after pancreatic surgery. These include collaborative projects, clinical auditing, and implementation of an algorithm for early recognition and management of postoperative complications. However, nationwide changes in outcome over time have not yet been described. METHODS: This nationwide cohort study included consecutive patients after pancreatoduodenectomy and distal pancreatectomy from the mandatory Dutch Pancreatic Cancer Audit (January 2014-December 2019). Patient, tumor, and treatment characteristics were compared between three time periods (2014-2015, 2016-2017, and 2018-2019). Short-term surgical outcome was investigated using multilevel multivariable logistic regression analyses. Primary endpoints were failure to rescue and in-hospital mortality. RESULTS: Overall, 5345 patients were included, of whom 4227 after pancreatoduodenectomy and 1118 after distal pancreatectomy. After pancreatoduodenectomy, failure to rescue improved from 13% to 7.4% (OR 0.64, 95%CI 0.50-0.80, P75 years (18% to 22%, P=0.006), ASA score ≥3 (19% to 31%, P

The aim of this study was to assess the clinical impact and risk factors of chyle leak (CL).In 2017, the International Study Group for Pancreatic Surgery (ISGPS) published the consensus definition of CL. Multicenter series validating this definition are lacking and previous studies investigating risk factors have used different definitions and showed heterogeneous results.This observational cohort study included all consecutive patients after pancreatoduodenectomy in all 19 centers in the mandatory nationwide Dutch Pancreatic Cancer Audit (2017-2019). The primary endpoint was CL (ISGPS grade B/C). Multivariable logistic regression analyses were performed.Overall, 2159 patients after pancreatoduodenectomy were included. The rate of CL was 7.0% (n=152), including 6.9% (n=150) grade B and 0.1% (n=2) grade C. CL was independently associated with a prolonged hospital stay [odds ratio (OR)=2.84, 95% confidence interval (CI): 1.85-4.36, P0.001] but not with mortality (OR=0.3, 95% CI: 0.0-2.3, P=0.244). In multivariable analyses, independent predictors for CL were vascular resection (OR=2.1, 95% CI: 1.4-3.2, P0.001) and open surgery (OR=3.5, 95% CI: 1.7-7.2, P=0.001). The number of resected lymph nodes and aortocaval lymph node sampling were not identified as predictors in multivariable analysis.In this nationwide analysis, the rate of ISGPS grade B/C CL after pancreatoduodenectomy was 7.0%. Although CL is associated with a prolonged hospital stay, the clinical impact is relatively minor in the vast majority (98%) of patients. Vascular resection and open surgery are predictors of CL.

ObjectiveWe aimed to determine the long-term yield of pancreatic cancer surveillance in hereditary predisposed high-risk individuals.DesignFrom 2006 to 2019, we prospectively enrolled asymptomatic individuals with an estimated 10% or greater lifetime risk of pancreatic ductal adenocarcinoma (PDAC) after obligatory evaluation by a clinical geneticist and genetic testing, and subjected them to annual surveillance with both endoscopic ultrasonography (EUS) and MRI/cholangiopancreatography (MRI/MRCP) at each visit.Results366 individuals (201 mutation-negative familial pancreatic cancer (FPC) kindreds and 165 PDAC susceptibility gene mutation carriers; mean age 54 years, SD 9.9) were followed for 63 months on average (SD 43.2). Ten individuals developed PDAC, of which four presented with a symptomatic interval carcinoma and six underwent resection. The cumulative PDAC incidence was 9.3% in the mutation carriers and 0% in the FPC kindreds (pConclusionThe diagnostic yield of PDAC was substantial in established high-risk mutation carriers, but non-existent in the mutation-negative proven FPC kindreds. Nevertheless, timely identification of resectable lesions proved challenging despite the concurrent use of two imaging modalities, with EUS outperforming MRI/MRCP. Overall, surveillance by imaging yields suboptimal results with a clear need for more sensitive diagnostic markers, including biomarkers.

Background Early recognition and management of postoperative complications, before they become clinically relevant, can improve postoperative outcomes for patients, especially for high-risk procedures such as pancreatic resection. Methods We did an open-label, nationwide, stepped-wedge cluster-randomised trial that included all patients having pancreatic resection during a 22-month period in the Netherlands. In this trial design, all 17 centres that did pancreatic surgery were randomly allocated for the timing of the crossover from usual care (the control group) to treatment given in accordance with a multimodal, multidisciplinary algorithm for the early recognition and minimally invasive management of postoperative complications (the intervention group). Randomisation was done by an independent statistician using a computer-generated scheme, stratified to ensure that low-medium-volume centres alternated with high-volume centres. Patients and investigators were not masked to treatment. A smartphone app was designed that incorporated the algorithm and included the daily evaluation of clinical and biochemical markers. The algorithm determined when to do abdominal CT, radiological drainage, start antibiotic treatment, and remove abdominal drains. After crossover, clinicians were trained in how to use the algorithm during a 4-week wash-in period; analyses comparing outcomes between the control group and the intervention group included all patients other than those having pancreatic resection during this wash-in period. The primary outcome was a composite of bleeding that required invasive intervention, organ failure, and 90-day mortality, and was assessed by a masked adjudication committee. This trial was registered in the Netherlands Trial Register, NL6671. Findings From Jan 8, 2018, to Nov 9, 2019, all 1805 patients who had pancreatic resection in the Netherlands were eligible for and included in this study. 57 patients who underwent resection during the wash-in phase were excluded from the primary analysis. 1748 patients (885 receiving usual care and 863 receiving algorithm-centred care) were included. The primary outcome occurred in fewer patients in the algorithm-centred care group than in the usual care group (73 [8%] of 863 patients vs 124 [14%] of 885 patients; adjusted risk ratio [RR] 0middot48, 95% CI 0middot38-0middot61; p

Background: Surgical outcome after pancreatoduodenectomy for duodenal adenocarcinoma could differ from pancreatoduodenectomy for other cancers, but large multicenter series are lacking. This study aimed to determine surgical outcome in patients after pancreatoduodenectomy for duodenal adenocarcinoma, compared with other periampullary cancers, in a nationwide multicenter cohort. Methods: After pancreatoduodenectomy for cancer between 2014 and 2019, consecutive patients were included from the nationwide, mandatory Dutch Pancreatic Cancer Audit. Patients were stratified by diagnosis. Baseline, treatment characteristics, and postoperative outcome were compared between groups. The association between diagnosis and major complications (Clavien–Dindo grade III or higher) was assessed via multivariable regression analysis. Results: Overall, 3113 patients, after pancreatoduodenectomy for cancer, were included in this study: 264 (8.5%) patients with duodenal adenocarcinomas and 2849 (91.5%) with other cancers. After pancreatoduodenectomy for duodenal adenocarcinoma, patients had higher rates of major complications (42.8% vs. 28.6%; p

In high-risk individuals participating in a pancreatic cancer surveillance program, worrisome features warrant for intensified surveillance or, occasionally, surgery. Our objectives were to determine the patient-reported burden of intensified surveillance and/or surgery, and to assess post-operative quality of life and opinion of surgery. Participants in our pancreatic cancer surveillance program completed questionnaires including the Cancer Worry Scale (CWS) and the Hospital Anxiety and Depression Scale (HADS). For individuals who underwent intensified surveillance, questionnaires before, during, and ≥ 3 weeks after were analyzed. In addition, subjects who underwent intensified surveillance in the past 3 years or underwent surgery at any time, were invited for an interview, that included the Short-Form 12 (SF-12). A total of 31 high-risk individuals were studied. During the intensified surveillance period, median CWS scores were higher (14, IQR 7), as compared to before (12, IQR 9, P = 0.007) and after (11, IQR 7, P = 0.014), but eventually returned back to baseline (P = 0.823). Median HADS scores were low: 5 (IQR 6) for anxiety and 3 (IQR 5) for depression, and they were unaffected by the intensified surveillance period. Of the 10 operated patients, 1 (10%) developed diabetes and 7 (70%) pancreatic exocrine insufficiency. The interviews yielded median quality-of-life scores comparable to the general population. Also, after surgery, patients’ attitudes towards surveillance were unchanged (5/10, 50%) or became more positive (4/10, 40%). Although patients were aware of the (sometimes benign) pathological outcome, when asked if surgery had been justified, only 20% (2/10) disagreed, and all would again have chosen to undergo surgery. In conclusion, in individuals at high risk for pancreatic cancer, intensified surveillance temporarily increased cancer worries, without affecting general anxiety or depression. Although pancreatic surgery led to substantial co-morbidity, quality of life was similar to the general population, and surgery did not negatively affect the attitude towards surveillance. Electronic supplementary material The online version of this article (10.1007/s10689-020-00171-8) contains supplementary material, which is available to authorized users.

Background: This study sought to assess patient satisfaction and quality of life (QoL) before and after treatment of pancreatic and periampullary cancer. Methods: We conducted a prospective multicenter study of patients treated for pancreatic and periampullary cancer. General patient satisfaction was measured using the EORTC satisfaction with care questionnaire (IN-PATSAT32) at baseline and 3 months after treatment initiation, with a 10-point change on the Likert scale considered clinically meaningful. QoL was measured using the EORTC Core Quality of Life Questionnaire (QLQ-C30). The influence of treatment (curative and palliative) on patient satisfaction and QoL was determined. Results: Of 100 patients, 71 completed follow-up questionnaires. General satisfaction with care decreased from 74.3 before treatment to 61.9 after treatment (PP=.39). Clinically meaningful reductions were also observed for the reported interpersonal skills of doctors (from 73.4 to 63.3) and exchange of information within the care team (from 63.5 to 52.5). Satisfaction scores were lower for patients treated with curative intent than for those treated with palliative intent regarding interpersonal skills of doctors (P=.01), information provision by doctors (P=.004), information provision by nurses (P=.02), availability of nurses (P=.004), exchange of information within the care team (P=.01), and hospital access (P=.02). In multivariable analysis, clinicopathologic or QoL factors were not independently associated with general patient satisfaction. Conclusions: Satisfaction with care, but not QoL, decreased after pancreatic cancer treatment. Improvements in communication and interpersonal skills are needed to maintain patient satisfaction after treatment.

Locally advanced pancreatic cancer (LAPC) has several definitions but essentially is a nonmetastasized pancreatic cancer, in which upfront resection is considered not beneficial due to extensive vascular involvement and consequent high chance of a nonradical resection. The introduction of FOLFIRINOX chemotherapy and gemcitabine-nab-paclitaxel (gem-nab) has had major implications for the management and outcome of patients with LAPC. After 4–6 months induction chemotherapy, the majority of patients have stable disease or even tumor-regression. Of these, 12 to 35% are successfully downstaged to resectable disease. Several studies have reported a 30–35 months overall survival after resection; although it currently remains unclear if this is a result of the resection or the good response to chemotherapy. Following chemotherapy, selection of patients for resection is difficult, as contrast-enhanced computed-tomography (CT) scan is unreliable in differentiating between viable tumor and fibrosis. In case a resection is not considered possible but stable disease is observed, local ablative techniques are being studied, such as irreversible electroporation, radiofrequency ablation, and stereotactic body radiation therapy. Pragmatic, multicenter, randomized studies will ultimately have to confirm the exact role of both surgical exploration and ablation in these patients. Since evidence-based guidelines for the management of LAPC are lacking, this review proposes a standardized approach for the treatment of LAPC based on the best available evidence.

Item does not contain fulltext BACKGROUND: Auditing is an important tool to identify practice variation and 'best practices'. The Dutch Pancreatic Cancer Audit is mandatory in all 18 Dutch centers for pancreatic surgery. METHODS: Performance indicators and case-mix factors were identified by a PubMed search for randomized controlled trials (RCT's) and large series in pancreatic surgery. In addition, data dictionaries of two national audits, three institutional databases, and the Dutch national cancer registry were evaluated. Morbidity, mortality, and length of stay were analyzed of all pancreatic resections registered during the first two audit years. Case ascertainment was cross-checked with the Dutch healthcare inspectorate and key-variables validated in all centers. RESULTS: Sixteen RCT's and three large series were found. Sixteen indicators and 20 case-mix factors were included in the audit. During 2014-2015, 1785 pancreatic resections were registered including 1345 pancreatoduodenectomies. Overall in-hospital mortality was 3.6%. Following pancreatoduodenectomy, mortality was 4.1%, Clavien-Dindo grade >/= III morbidity was 29.9%, median (IQR) length of stay 12 (9-18) days, and readmission rate 16.0%. In total 97.2% of >40,000 variables validated were consistent with the medical charts. CONCLUSIONS: The Dutch Pancreatic Cancer Audit, with high quality data, reports good outcomes of pancreatic surgery on a national level.

Item does not contain fulltext OBJECTIVES: Severe acute pancreatitis is associated with peripancreatic morphologic changes as seen on imaging. Uniform communication regarding these morphologic findings is crucial for accurate diagnosis and treatment. For the original 1992 Atlanta classification, interobserver agreement is poor. We hypothesized that for the revised Atlanta classification, interobserver agreement will be better. METHODS: An international, interobserver agreement study was performed among expert and nonexpert radiologists (n = 14), surgeons (n = 15), and gastroenterologists (n = 8). Representative computed tomographies of all stages of acute pancreatitis were selected from 55 patients and were assessed according to the revised Atlanta classification. The interobserver agreement was calculated among all reviewers and subgroups, that is, expert and nonexpert reviewers; interobserver agreement was defined as poor (

Item does not contain fulltext BACKGROUND: Diagnosing infected necrotizing pancreatitis (INP) may be challenging. The aim of this study was to determine the added value of routine fine-needle aspiration (FNA) in addition to clinical and imaging signs of infection in patients who underwent intervention for suspected INP. METHODS: We conducted a post hoc analysis of 208 consecutive patients from a prospective, multicenter database who underwent intervention because of suspected INP. In retrospect, 3 groups were constructed based on the patients preoperative characteristics: Clinical, imaging, and FNA. Patients in the clinical group had clinical signs of infection but no gas on preoperative computed tomography (CT) and no FNA performed before intervention. Patients in the imaging group had gas bubbles on the preoperative CT but no was FNA performed, whereas patients in the FNA group had a positive FNA before intervention. The reference standard for infection was the culture taken during the first intervention (either catheter drainage or necrosectomy). RESULTS: The initial intervention for INP was performed a median of 27 days (interquartile range, 20-39) after admission without difference between the 3 groups (P = .15). Infection was confirmed in 80% of 92 patients of the clinical group, in 94% of 88 patients of the imaging group, and in 86% of 28 patients of the FNA group (P = .07). Mortality was 19% and was not different between groups (P = .39). CONCLUSION: INP can generally be diagnosed based on clinical or imaging signs of infection. FNA may be useful in patients with unclear clinical signs and no imaging signs of INP.

Understanding the mechanisms of immune resistance in pancreatic and ampullary cancers is crucial for the development of suitable biomarkers and effective immunotherapeutics. Our aim was to examine the expression of the immune inhibiting molecules PD-L1, Galectin-9, HVEM, IDO and HLA-G, as well as CD8+ and FoxP3+ tumor infiltrating lymphocytes (TIL), in pancreatic and ampullary cancers, and to relate their individual, as well as their combined expression, to cancer survival. Tumor tissue from 224 patients with resected pancreatic (n = 148) and ampullary (n = 76) cancer was used to construct tissue-microarrays. Expression of immune inhibitory molecules and TIL was examined by immunohistochemistry. We show that immune inhibitory molecules are prevalently expressed. Moreover, high tumor expression of PD-L1 (p = 0.002), Gal-9 (p = 0.003), HVEM (p = 0.001), IDO (p = 0.049), HLA-G (p = 0.004) and high CD8/FoxP3 TIL ratio (p = 0.006) were associated with improved cancer-specific survival. All immune biomarkers, with the exception of IDO, were individually predictive of cancer-specific survival when adjusted for clinicopathologic characteristics. For every additional immune biomarker present survival was almost two-fold prolonged (HR 0.57 95%CI 0.47-0.69, p 0.0001). When patients with pancreatic and ampullary cancer were analyzed separately the results were similar. We conclude that pancreas and ampullary cancers are rich in expression of immune-inhibitory molecules. These molecules can be targets for future immunotherapeutics, as well as form powerful immunological biomarkers. We propose that such immune biomarker panels be included in future prospective immunotherapy trials.

Item does not contain fulltext BACKGROUND: The optimal diagnostic strategy and timing of intervention in infected necrotizing pancreatitis is subject to debate. We performed a survey on these topics amongst a group of international expert pancreatologists. METHODS: An online survey including case vignettes was sent to 118 international pancreatologists. We evaluated the use and timing of fine needle aspiration (FNA), antibiotics, catheter drainage and (minimally invasive) necrosectomy. RESULTS: The response rate was 74% (N = 87). None of the respondents use FNA routinely, 85% selectively and 15% never. Most respondents (87%) use a step-up approach in patients with infected necrosis. Walled-off necrosis (WON) is considered a prerequisite for endoscopic drainage and percutaneous drainage by 66% and 12%, respectively. After diagnosing infected necrosis, 55% routinely postpone invasive interventions, whereas 45% proceed immediately to intervention. Lack of consensus about timing of intervention was apparent on day 14 with proven infected necrosis (58% intervention vs. 42% non-invasive) as well as on day 20 with only clinically suspected infected necrosis (59% intervention vs. 41% non-invasive). DISCUSSION: The step-up approach is the preferred treatment strategy in infected necrotizing pancreatitis amongst expert pancreatologists. There is no uniformity regarding the use of FNA and timing of intervention in the first 2-3 weeks of infected necrotizing pancreatitis.

Contains fulltext : 80886.pdf (Publisher’s version ) (Closed access) SUMMARY BACKGROUND DATA: The role of early endoscopic retrograde cholangiopancreatography (ERCP) in acute biliary pancreatitis (ABP) remains controversial. Previous studies have included only a relatively small number of patients with predicted severe ABP. We investigated the clinical effects of early ERCP in these patients. METHODS: We performed a prospective, observational multicenter study in 8 university medical centers and 7 major teaching hospitals. One hundred fifty-three patients with predicted severe ABP without cholangitis enrolled in a randomized multicenter trial on probiotic prophylaxis in acute pancreatitis were prospectively followed. Conservative treatment or ERCP within 72 hours after symptom onset (at discretion of the treating physician) were compared for complications and mortality. Patients without and with cholestasis (bilirubin: >2.3 mg/dL [40 mumol/L] and/or dilated common bile duct) were analyzed separately. RESULTS: Of the 153 patients, 81 (53%) underwent ERCP and 72 (47%) conservative treatment. Groups were highly comparable at baseline. Seventy-eight patients (51%) had cholestasis. In patients with cholestasis, ERCP (52/78 patients: 67%), as compared with conservative treatment, was associated with fewer complications (25% vs. 54%, P = 0.020, multivariate adjusted odds ratio [OR]: 0.35, 95% confidence interval [CI]: 0.13-0.99, P= 0.049). This included fewer patients with >30% pancreatic necrosis (8% vs. 31%, P = 0.010). Mortality was nonsignificantly lower after ERCP (6% vs. 15%, P = 0.213, multivariate adjusted OR: 0.44, 95% CI: 0.08-2.28, P = 0.330). In patients without cholestasis, ERCP (29/75 patients: 39%) was not associated with reduced complications (45% vs. 41%, P = 0.814, multivariate adjusted OR: 1.36; 95% CI: 0.49-3.76; P = 0.554) or mortality (14% vs. 17%, P = 0.754, multivariate adjusted OR: 0.78; 95% CI: 0.19-3.12, P = 0.734). CONCLUSIONS: Early ERCP is associated with fewer complications in predicted severe ABP if cholestasis is present.

To evaluate the indications, complications and survival after pancreatoduodenectomy, with special attention for the outcome after extended resection due to tumour extension and in elderly patients.Retrospective, partly cross-sectional study.All 275 consecutive adult patients who underwent explorative laparotomy for a suspected resectable pancreatic head tumour or periampulary tumour in two Dutch tertiary centres between 2007 and 2010 were included. We graded the postoperative complications according to international classifications and collected data on survival.In 218/275 patients (79%) the tumour could be resected by pancreatoduodenectomy with or without an extended resection. Malignancy was confirmed in 190/218 patients (87%); in 153/190 patients (81%) a microscopically radical (R0) resection was achieved. Fifteen percent of the patients required a re-intervention (radiological, endoscopic or surgical) because of an intra-abdominal complication. The post-operative 30-day mortality was 4.1%. Eighty-six patients (39%) were ultimately diagnosed with 'pancreatic adenocarcinoma'; they had a 1- and 2-year survival rate of 63% and 34%, respectively. In 27 patients (12%) who underwent an extended resection for oncological reasons, such as partial hepatic portal vein resection, the 30-day mortality was 0% and the survival rates were comparable to patients with a standard resection. The 81 patients (37%) aged 70 or older had a 30-day mortality and survival similar to younger patients.More than 75% of potentially resectable tumours were resected by a pancreatoduodenectomy with or without an extended resection, with a relatively low postoperative mortality and an adequate survival benefit. After multidisciplinary assessment, both limited tumour extension and a higher age are not necessarily contraindications for a resection, as a comparable survival benefit can be obtained for these groups of patients as for other groups.

Epidemiological research consistently shows a female advantage in melanoma survival. So far, no definite candidate for the explanation of this phenomenon has emerged. We propose that gender differences in oxidative stress caused by radical oxygen species (ROS) underlie these survival differences. It is known that males express lower amounts of anti-oxidant enzymes, resulting in more oxidative stress than females. The primary melanoma environment is characterized by high ROS levels, from exogenous sources as well as ROS production within melanoma cells themselves. ROS are known to be able to promote metastasis through a wide variety of mechanisms. We hypothesize that the higher levels of ROS in men enhance selection of ROS-resistance in melanoma cells. Subsequently, ROS can stimulate the metastatic potential of melanoma cells. In addition, due to the lower anti-oxidant defenses in men, ROS produced by melanoma cells cause more damage to healthy tissues surrounding the tumor, further stimulating metastasis. Therefore, ROS may explain the observed differences between males and females in melanoma survival.