Search

Background The aim of the study was to evaluate the current opinion and clinical decision-making process of international pancreatologists, and to systematically identify key study questions regarding the diagnosis and treatment of chronic pancreatitis (CP) for future research. Methods An online survey, including questions regarding the diagnosis and treatment of CP and several controversial clinical case vignettes, was send by e-mail to members of various international pancreatic associations: IHPBA, APA, EPC, ESGE and DPSG. Results A total of 288 pancreatologists, 56% surgeons and 44% gastroenterologists, from at least 47 countries, participated in the survey. About half (48%) of the specialists used a classification tool for the diagnosis of CP, including the Mayo Clinic (28%), Mannheim (25%), or Büchler (25%) tools. Overall, CT was the preferred imaging modality for evaluation of an enlarged pancreatic head (59%), pseudocyst (55%), calcifications (75%), and peripancreatic fat infiltration (68%). MRI was preferred for assessment of main pancreatic duct (MPD) abnormalities (60%). Total pancreatectomy with auto-islet transplantation was the preferred treatment in patients with parenchymal calcifications without MPD abnormalities and in patients with refractory pain despite maximal medical, endoscopic, and surgical treatment. In patients with an enlarged pancreatic head, 58% preferred initial surgery (PPPD) versus 42% initial endoscopy. In patients with a dilated MPD and intraductal stones 56% preferred initial endoscopic ± ESWL treatment and 29% preferred initial surgical treatment. Conclusion Worldwide, clinical decision-making in CP is largely based on local expertise, beliefs and disbeliefs. Further development of evidence-based guidelines based on well designed (randomized) studies is strongly encouraged. [ABSTRACT FROM AUTHOR]

Background: The additional value of perioperative antibiotic prophylaxis in preventing infectious complications after emergency cholecystectomy for acute cholecystitis is a much-debated subject in the surgical community. Evidence-based guidelines are lacking, and consequently the use of antibiotic prophylaxis varies greatly among surgeons and hospitals. Recently, high-level evidence became available demonstrating that postoperative antibiotic prophylaxis in patients with acute cholecystitis does not reduce the risk of infectious complications. Preoperative antibiotic prophylaxis in relation to the risk of infectious complications, however, has never been studied.Methods: The PEANUTS II trial is a randomized, controlled, multicenter, open-label noninferiority trial whose aim is to determine the utility of preoperative antibiotic prophylaxis in patients undergoing emergency cholecystectomy for acute calculous cholecystitis. Patients with mild or moderate acute cholecystitis, as defined according the Tokyo Guidelines, will be randomly assigned to a single preoperative dose of antibiotic prophylaxis (2000 mg of first-generation cephalosporin delivered intravenously) or no antibiotic prophylaxis before emergency cholecystectomy. The primary endpoint is a composite endpoint consisting of all postoperative infectious complications occurring during the first 30 days after surgery. Secondary endpoints include all the individual components of the primary endpoint, all other complications, duration of hospital stay, and total costs. The hypothesis is that the absence of antibiotic prophylaxis is noninferior to the presence of antibiotic prophylaxis. A noninferiority margin of 10% is assumed. With a 1-sided risk of 2.5% and a power of 80%, a total of 454 subjects will have to be included. Analysis will be performed according to the intention-to-treat principle.Discussion: The PEANUTS II trial will provide evidence-based advice concerning the utility of antibiotic prophylaxis in patients undergoing emergency cholecystectomy for acute calculous cholecystitis.Trial Registration: Netherlands Trial Register, NTR5802 . Registered on 4 June 2016. [ABSTRACT FROM AUTHOR]

Background The majority of patients who have undergone a pancreatic resection for pancreatic cancer develop disease recurrence within two years. In around 30% of these patients, isolated local recurrence (ILR) is found. The aim of this study was to systematically review treatment options for this subgroup of patients. Methods A systematic search was performed in PubMed, Embase and the Cochrane Library. Studies reporting on the treatment of ILR after initial curative-intent resection of primary pancreatic cancer were included. Primary endpoints were morbidity, mortality and survival after ILR treatment. Results After screening 1152 studies, 18 studies reporting on 313 patients undergoing treatment for ILR were included. Treatment options for ILR included surgical re-resection (8 studies, 100 patients), chemoradiotherapy (7 studies, 153 patients) and stereotactic body radiation therapy (SBRT) (4 studies, 60 patients). Morbidity and mortality were reported for re-resection (29% and 1%, respectively), chemoradiotherapy (54% and 0%) and SBRT (3% and 1%). Most patients had a prolonged disease-free interval before recurrence. Median survival after treatment of ILR of up to 32, 19 and 16 months was reported for re-resection, chemoradiotherapy and SBRT, respectively. Conclusion In selected patients, treatment of ILR following pancreatic resection for pancreatic cancer seems safe, feasible and associated with relatively good survival. [ABSTRACT FROM AUTHOR]

Objectives: Computed tomography (CT) is the most widely used method to assess resectability of pancreatic and peri-ampullary cancer. One of the contra-indications for curative resection is the presence of extra-regional lymph node metastases. This meta-analysis investigates the accuracy of CT in assessing extra-regional lymph node metastases in pancreatic and peri-ampullary cancer. Methods: We systematically reviewed the literature according to the PRISMA guidelines. Studies reporting on CT assessment of extra-regional lymph nodes in patients undergoing pan-creatoduodenectomy were included. Data on baseline characteristics, CT-investigations and histopath-ological outcomes were extracted. Diagnostic accuracy, positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity were calculated for individual studies and pooled data. Results: After screening, 4 cohort studies reporting on CT-findings and histopathological outcome in 157 patients with pancreatic or peri-ampullary cancer were included. Overall, diagnostic accuracy, specificity and NPV varied from 63 to 81, 80-100% and 67-90% respectively. However, PPV and sensitivity ranged from 0 to 100% and 0-38%. Pooled sensitivity, specificity, PPV and NPV were 25%, 86%, 28% and 84% respectively. Conclusions: CT has a low diagnostic accuracy in assessing extra-regional lymph node metastases in pancreatic and peri-ampullary cancer. Therefore, suspicion of extra-regional lymph node metastases on CT alone should not be considered a contra-indication for exploration [ABSTRACT FROM AUTHOR]

The article discusses a randomized study of the proinflammatory response (PR) and clinical outcome of endoscopic transgastric (ET) and surgical necrosectomy (SN) for patients with infected necrotizing pancreatitis (INP). The researchers randomized 22 patients with signs of INP and had an indication for intervention in 3 academic hospitals and one regional teaching hospital in the Netherlands between August 20, 2008 and March 3, 2010. They found that ET lowered the PR and the composite clinical end point compared with SN. INSET: Box. Definitions of Clinical End Points.

Background: In predicted severe acute pancreatitis, infections have a negative effect on clinical outcome. A start of enteral nutrition (EN) within 24 hours of onset may reduce the number of infections as compared to the current practice of starting an oral diet and EN if necessary at 3-4 days after admission. Methods/Design: The PYTHON trial is a randomised controlled, parallel-group, superiority multicenter trial. Patients with predicted severe acute pancreatitis (Imrie-score = 3 or APACHE-II score = 8 or CRP > 150 mg/L) will be randomised to EN within 24 hours or an oral diet and EN if necessary, after 72 hours after hospital admission. During a 3-year period, 208 patients will be enrolled from 20 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite of mortality or infections (bacteraemia, infected pancreatic or peripancreatic necrosis, pneumonia) during hospital stay or within 6 months following randomisation. Secondary endpoints include other major morbidity (e.g. new onset organ failure, need for intervention), intolerance of enteral feeding and total costs from a societal perspective. Discussion: The PYTHON trial is designed to show that a very early (< 24 h) start of EN reduces the combined endpoint of mortality or infections as compared to the current practice of an oral diet and EN if necessary at around 72 hours after admission for predicted severe acute pancreatitis. [ABSTRACT FROM AUTHOR]

Background: Necrotizing pancreatitis with infected necrotic tissue is associated with a high rate of complications and death. Standard treatment is open necrosectomy. The outcome may be improved by a minimally invasive step-up approach. Methods: In this multicenter study, we randomly assigned 88 patients with necrotizing pancreatitis and suspected or confirmed infected necrotic tissue to undergo primary open necrosectomy or a step-up approach to treatment. The step-up approach consisted of percutaneous drainage followed, if necessary, by minimally invasive retroperitoneal necrosectomy. The primary end point was a composite of major complications (new-onset multiple-organ failure or multiple systemic complications, perforation of a visceral organ or enterocutaneous fistula, or bleeding) or death. Results: The primary end point occurred in 31 of 45 patients (69%) assigned to open necrosectomy and in 17 of 43 patients (40%) assigned to the step-up approach (risk ratio with the step-up approach, 0.57; 95% confidence interval, 0.38 to 0.87; P=0.006). Of the patients assigned to the step-up approach, 35% were treated with percutaneous drainage only. New-onset multiple-organ failure occurred less often in patients assigned to the step-up approach than in those assigned to open necrosectomy (12% vs. 40%, P=0.002). The rate of death did not differ significantly between groups (19% vs. 16%, P=0.70). Patients assigned to the step-up approach had a lower rate of incisional hernias (7% vs. 24%, P=0.03) and new-onset diabetes (16% vs. 38%, P=0.02). Conclusions: A minimally invasive step-up approach, as compared with open necrosectomy, reduced the rate of the composite end point of major complications or death among patients with necrotizing pancreatitis and infected necrotic tissue. (Current Controlled Trials number, ISRCTN13975868.) N Engl J Med 2010;362:1491-502. [ABSTRACT FROM AUTHOR]

The article focuses on research which examined probiotic prophylaxis in predicted severe acute pancreatitis. In the research 298 patients with predicted severe acute pancreatitis were studied. researchers found that in patients with predicted severe acute pancreatitis, probiotic prophylaxis with a combination of probiotic strains did not reduce the risk of infectious complications and was also associated with an increased risk of mortality. Researchers suggested that probiotic prophylaxis should not be administered in patients with predicted severe acute pancreatitis.

BACKGROUND: Oral refeeding in patients recovering from acute pancreatitis may cause pain relapse. Patients with pain relapse may be ill for prolonged periods, thereby consuming additional health care resources. We aimed to determine the incidence and risk factors of pain relapse on the basis of reviewing all studies on oral refeeding in acute pancreatitis. METHODS: Relevant literature cited in three electronic databases (Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE) as well as the abstracts of major gastroenterological meetings was reviewed. Outcome measures studied were the incidence of pain relapse and length of hospital stay. RESULTS: A total of three studies met the inclusion criteria. Sixty of 274 patients (21.9%) experienced pain relapse during the course of acute pancreatitis. In 47 of 60 (78.3%) patients pain relapse occurred within 48 h after commencement of oral refeeding. Two studies showed a significantly higher Balthazar's CT score on hospital admission in patients with pain relapse, whereas all three studies found no difference in the severity scores between patients with and without pain relapse. All three studies found a significant increase in the length of hospital stay in patients with pain relapse. CONCLUSIONS: The incidence of pain relapse after oral refeeding in acute pancreatitis is relatively high. Thereby, the quest for new therapeutical modalities that can prevent pain relapse is of current importance. [ABSTRACT FROM AUTHOR]

Minimally invasive necrosectomy through a retroperitoneal approach is gaining popularity for the treatment of necrotizing pancreatitis. There is, however, no substantial evidence from comparative studies in favor of this technique over laparotomy. The aim of this case-matched study was to perform the first head-to-head comparison of necrosectomy by the retroperitoneal approach with laparotomy in patients with necrotizing pancreatitis. Between 2001 and 2005, there were 15 of 841 consecutive acute pancreatitis patients who underwent necrosectomy by the retroperitoneal approach using a small flank incision. These patients were matched for the presence of preoperative organ failure, status of infection, timing of surgery, age, and computed tomography severity index score with 15 of 46 patients treated with necrosectomy by laparotomy and continuous postoperative lavage (CPL). In addition to all matched preoperative characteristics, there were no significant differences in sex, preoperative intensive care unit (ICU) admission, preoperative ICU stay, preoperative APACHE-II scores, and preoperative multiple organ failure (MOF). Postoperative complications requiring reintervention occurred in six patients in each group ( p = 1.000). Postoperative new-onset MOF occurred in 10 patients in the laparotomy/CPL group versus 2 patients in the retroperitoneal approach group ( p = 0.008). Six patients died in the laparotomy/CPL group versus 1 patient in the retroperitoneal approach group ( p = 0.080). The less postoperative organ failure and the trend toward lower mortality may point to a benefit of the retroperitoneal approach over laparotomy. A randomized controlled design is, however, still required to answer definitively the question of which operative technique is preferably for patients with (infected) necrotizing pancreatitis. [ABSTRACT FROM AUTHOR]

Radiation therapy (RT) initiates a local and systemic immune response which can induce antitumor immunity and improve immunotherapy efficacy. Neutrophils are among the first immune cells that infiltrate tumors after RT and are suggested to be essential for the initial antitumor immune response. However, neutrophils in tumors are associated with poor outcomes and RT-induced neutrophil infiltration could also change the composition of the tumor microenvironment (TME) in favor of tumor progression. To improve RT efficacy for patients with cancer it is important to understand the interplay between RT and neutrophils. Here, we review the literature on how RT affects the infiltration and function of neutrophils in the TME of solid tumors, using both patients studies and preclinical murine in vivo models. In general, it was found that neutrophil levels increase and reach maximal levels in the first days after RT and can remain elevated up to 3 weeks. Most studies report an immunosuppressive role of neutrophils in the TME after RT, caused by upregulated expression of neutrophil indoleamine 2,3-dioxygenase 1 and arginase 1, as well as neutrophil extracellular trap formation. RT was also associated with increased reactive oxygen species production by neutrophils, which can both improve and inhibit antitumor immunity. In addition, multiple murine models showed improved RT efficacy when depleting neutrophils, suggesting that neutrophils have a protumor phenotype after RT. We conclude that the role of neutrophils should not be overlooked when developing RT strategies and requires further investigation in specific tumor types. In addition, neutrophils can possibly be exploited to enhance RT efficacy by combining RT with neutrophil-targeting therapies. [ABSTRACT FROM AUTHOR]

Background & Aims: Endoscopic retrograde cholangiopancreatography (ERCP) with brush cytology is an important tool in the diagnosis of hepatobiliary malignancies. However, reported sensitivity of brush cytology is suboptimal and differs markedly per study. The aim of this study is to analyze the optimal technique of endobiliary brushing during ERCP. Methods: A systematic review and meta-analysis according was performed using Pubmed, Embase and Cochrane library, and reported reported according to the PRISMA guidelines. The intervention reported should involve ERCP, performed by the endoscopist with a comparison of different brushing techniques. The primary outcome was sensitivity for malignancy. Studies published up to December 2022 were included. Percutaneous techniques and cytological or laboratory techniques for processing of material were excluded. Bias was assessed using the Quadas-2 tool. Pooled sensitivity rates and Forest plots were analyzed for the primary outcome. Results: A total of 16 studies were included. Three studies reported on brushing before or after dilation of a biliary stricture. No improvement in sensitivity was found. Five studies reported on alternative brush designs. This did not lead to improved sensitivity. Seven studies reported on the aspiration and analysis of bile fluid, which resulted in a 16% increase in sensitivity (95% CI 4-29%). One study reported an increased in the number of brush passes to the stricture, providing an increase in sensitivity of 20%. Substantial heterogeneity between studies was found, both methodological and statistical. Conclusions: Increasing the number of brush-passes and sending bile fluid for cytology increases the sensitivity of biliary brushings during ERCP. Dilation before brushing or alternative brush designs did not increase sensitivity. [ABSTRACT FROM AUTHOR]

BACKGROUND: The introduction of modern chemotherapy a decade ago has led to increased use of neoadjuvant therapy (NAT) in patients with pancreatic ductal adenocarcinoma (PDAC). A recent North American study demonstrated increased use of NAT and improved operative outcomes in patients with PDAC. The aims of this study were to compare the use of NAT and shortterm outcomes in patients with PDAC undergoing pancreatoduodenectomy (PD) among registries from the US and Canada, Germany, the Netherlands, and Sweden. STUDY DESIGN: Databases from 2 multicenter (voluntary) and 2 nationwide (mandatory) registries were queried from 2018 to 2020. Patients undergoing PD for PDAC were compared based on the use of upfront surgery vs NAT. Adoption of NAT was measured in each country over time. Thirty-day outcomes, including the composite measure (ideal outcomes), were compared by multivariable analyses. Sensitivity analyses of patients undergoing vascular resection were performed. RESULTS: Overall, 11,402 patients underwent PD for PDAC with 33.7% of patients receiving NAT. The use of NAT increased steadily from 28.3% in 2018 to 38.5% in 2020 (p < 0.0001). However, use of NAT varied widely by country: the US (46.8%), the Netherlands (44.9%), Sweden (11.0%), and Germany (7.8%). On multivariable analysis, NAT was significantly (p < 0.01) associated with reduced rates of serious morbidity, clinically relevant pancreatic fistulae, reoperations, and increased ideal outcomes. These associations remained on sensitivity analysis of patients undergoing vascular resection. CONCLUSIONS: NAT before PD for pancreatic cancer varied widely among 4 Western audits yet increased by 26% during 3 years. NAT was associated with improved short-term outcomes. [ABSTRACT FROM AUTHOR]

Treatment guidelines for splanchnic vein thrombosis in necrotizing pancreatitis are lacking due to insufficient data on the full clinical spectrum. We performed a post-hoc analysis of a nationwide prospective necrotizing pancreatitis cohort. Multivariable analyses were used to identify risk factors and compare the clinical course of patients with and without SVT. SVT was detected in 97 of the 432 included patients (22%) (median onset: 4 days). Risk factors were left, central, or subtotal necrosis (OR 28.52; 95% CI 20.11–40.45), right or diffuse necrosis (OR 5.76; 95% CI 3.89–8.51), and younger age (OR 0.94; 95% CI 0.90–0.97). Patients with SVT had higher rates of bleeding (n = 10,11%) and bowel ischemia (n = 4,4%) compared to patients without SVT (n = 14,4% and n = 2,0.6%; OR 3.24; 95% CI 1.27–8.23 and OR 7.29; 95% CI 1.31–40.4, respectively), and were independently associated with ICU admission (adjusted OR 2.53; 95% CI 1.37–4.68). Spontaneous recanalization occurred in 62% of patients (n = 40/71). Radiological and clinical outcomes did not differ between patients treated with and without anticoagulants. SVT is a common and early complication of necrotizing pancreatitis, associated with parenchymal necrosis and younger age. SVT is associated with increased complications and a worse clinical course, whereas anticoagulant use does not appear to affect outcomes. [ABSTRACT FROM AUTHOR]

Early detection of major complications after pancreatoduodenectomy could improve patient management and decrease the "failure-to-rescue" rate. In this retrospective cohort study, we aimed to compare the value of C-reactive protein (CRP) and white blood cell count (WBC) in the early detection of complications after pancreatoduodenectomy. We assessed pancreatoduodenectomies between January 2012 and December 2017. Major complications were defined as grade III or higher according to the Clavien-Dindo classification. Postoperative pancreatic fistula (POPF) was a secondary endpoint. ROC-curve and logistic regression analysis were performed for CRP and WBC. Results were validated in an external cohort. In the development cohort (n = 285), 103 (36.1%) patients experienced a major complication. CRP was superior to WBC in detecting major complications on postoperative day (POD) 3 (AUC:0.74 vs. 0.54, P < 0.001) and POD 5 (AUC:0.77 vs. 0.68, P = 0.031), however not on POD 7 (AUC:0.77 vs. 0.76, P = 0.773). These results were confirmed in multivariable analysis and in the validation cohort (n = 202). CRP was also superior to WBC in detecting POPF on POD 3 (AUC: 0.78 vs. 0.54, P < 0.001) and POD 5 (AUC: 0.83 vs. 0.71, P < 0.001). CRP appears to be superior to WBC in the early detection of major complications and POPF after pancreatoduodenectomy. [ABSTRACT FROM AUTHOR]

Background: Although robotic pancreatoduodenectomy has shown promising outcomes in experienced high-volume centres, it is unclear whether implementation on a nationwide scale is safe and beneficial. The aim of this study was to compare the outcomes of the early experience with robotic pancreatoduodenectomy versus open pancreatoduodenectomy in the Netherlands. Methods: This was a nationwide retrospective cohort study of all consecutive patients who underwent robotic pancreatoduodenectomy or open pancreatoduodenectomy who were registered in the mandatory Dutch Pancreatic Cancer Audit (18 centres, 2014–2021), starting from the first robotic pancreatoduodenectomy procedure per centre. The main endpoints were major complications (Clavien–Dindo grade greater than or equal to III) and in-hospital/30-day mortality. Propensity-score matching (1 : 1) was used to minimize selection bias. Results: Overall, 701 patients who underwent robotic pancreatoduodenectomy and 4447 patients who underwent open pancreatoduodenectomy were included. Among the eight centres that performed robotic pancreatoduodenectomy, the median robotic pancreatoduodenectomy experience was 86 (range 48–149), with a 7.3% conversion rate. After matching (698 robotic pancreatoduodenectomy patients versus 698 open pancreatoduodenectomy control patients), no significant differences were found in major complications (40.3% versus 36.2% respectively; P = 0.186), in-hospital/30-day mortality (4.0% versus 3.1% respectively; P = 0.326), and postoperative pancreatic fistula grade B/C (24.9% versus 23.5% respectively; P = 0.578). Robotic pancreatoduodenectomy was associated with a longer operating time (359 min versus 301 min; P < 0.001), less intraoperative blood loss (200 ml versus 500 ml; P < 0.001), fewer wound infections (7.4% versus 12.2%; P = 0.008), and a shorter hospital stay (11 days versus 12 days; P < 0.001). Centres performing greater than or equal to 20 robotic pancreatoduodenectomies annually had a lower mortality rate (2.9% versus 7.3%; P = 0.009) and a lower conversion rate (6.3% versus 11.2%; P = 0.032). Conclusion: This study indicates that robotic pancreatoduodenectomy was safely implemented nationwide, without significant differences in major morbidity and mortality compared with matched open pancreatoduodenectomy patients. Randomized trials should be carried out to verify these findings and confirm the observed benefits of robotic pancreatoduodenectomy versus open pancreatoduodenectomy. This nationwide study in 18 centres compared the surgical outcomes of 698 patients who underwent robotic pancreatoduodenectomy with those of 698 propensity-score-matched patients who underwent open pancreatoduodenectomy. The rates of major complications and mortality did not differ significantly, whereas robotic pancreatoduodenectomy was associated with less intraoperative blood loss, a longer operating time, a shorter hospital stay, fewer grade B/C chyle leaks, and fewer wound infections than open pancreatoduodenectomy. [ABSTRACT FROM AUTHOR]

Purpose: Distal pancreatectomy (DP) is associated with a high complication rate of 30–50% with postoperative pancreatic fistula (POPF) as a dominant contributor. Adequate risk estimation for POPF enables surgeons to use a tailor-made approach. Assessment of the risk of POPF prior to DP can lead to the application of preventive strategies. The current study aims to validate the recently published preoperative and intraoperative distal fistula risk score (D-FRS) in a nationwide cohort. Methods: This nationwide retrospective Dutch cohort study included all patients after DP for any indication, all of whom were registered in the Dutch Pancreatic Cancer Audit (DPCA) database between 2013 and 2021. The D-FRS was validated by filling in the probability equations with data from this cohort. The predictive capacity of the models was represented by an area under the receiver operating characteristic (AUROC) curve. Results: A total of 896 patients underwent DP of which 152 (17%) developed POPF of whom 144 grade B (95%) and 8 grade C (5%). The preoperative D-FRS, consisting of the variables pancreatic neck thickness and pancreatic duct diameter, showed an AUROC of 0.73 (95%CI 0.68–0.78). The intraoperative D-FRS, comprising pancreatic neck, duct diameter, BMI, operating time, and soft pancreatic aspect, showed an AUROC of 0.69 (95%CI 0.64–0.74). Conclusion: The current study is the first nationwide validation of the preoperative and intraoperative D-FRS showing acceptable distinguishing capacity for only the preoperative D-FRS for POPF. Therefore, the preoperative score could improve prevention and mitigation strategies such as drain management, which is currently investigated in the multicenter PANDORINA trial. [ABSTRACT FROM AUTHOR]

Simple Summary: The use of imaging, in general and during follow-up after resection of pancreatic cancer, is increasing. Consequently, the number of asymptomatic patients diagnosed with metastatic pancreatic cancer (mPDAC), both at initial diagnosis and during the diagnosis of recurrent disease, is increasing. In these patients, palliative systemic therapy is the only (tumor-directed) therapy and, hence, is often immediately initiated. However, delaying therapy until symptoms occur may preserve quality of life and avoid therapy-related toxicity, but the impact on survival of this approach is unknown. Using an online survey sent to all first and last authors of published trials on mPDAC and to medical oncologists of the Dutch Pancreatic Cancer group, this study aimed to gain insight into the current perspectives and clinical decision-making of experts. Overall, 78 of 291 (27%) medical oncologists from 15 countries responded. Two-thirds of respondents (63%) preferred an immediate initiation of chemotherapy following diagnosis. In 3/9 case-vignettes, delayed treatment was favored in specific clinical contexts (i.e., patient with only one small lung metastasis, significant comorbidities, and higher age). Respondents from the Netherlands, as well as medical oncologists with fewer years of experience, more often favored delayed treatment. Although the response rate was limited, in this increasing group of asymptomatic patients with mPDAC, immediate treatment is most often preferred, although in specific clinical contexts (i.e., limited metastatic disease, more comorbidities, and higher age), delaying treatment until symptoms occur is considered. Background: The use of imaging, in general, and during follow-up after resection of pancreatic cancer, is increasing. Consequently, the number of asymptomatic patients diagnosed with metastatic pancreatic cancer (mPDAC) is increasing. In these patients, palliative systemic therapy is the only tumor-directed treatment option; hence, it is often immediately initiated. However, delaying therapy in asymptomatic palliative patients may preserve quality of life and avoid therapy-related toxicity, but the impact on survival is unknown. This study aimed to gain insight into the current perspectives and clinical decision=making of experts regarding the timing of treatment initiation of patients with asymptomatic mPDAC. Methods: An online survey (13 questions, 9 case-vignettes) was sent to all first and last authors of published clinical trials on mPDAC over the past 10 years and medical oncologists of the Dutch Pancreatic Cancer Group. Inter-rater variability was determined using the Kappa Light test. Differences in the preferred timing of treatment initiation among countries, continents, and years of experience were analyzed using Fisher's exact test. Results: Overall, 78 of 291 (27%) medical oncologists from 15 countries responded (62% from Europe, 23% from North America, and 15% from Asia–Pacific). The majority of respondents (63%) preferred the immediate initiation of chemotherapy following diagnosis. In 3/9 case-vignettes, delayed treatment was favored in specific clinical contexts (i.e., patient with only one small lung metastasis, significant comorbidities, and higher age). A significant degree of inter-rater variability was present within 7/9 case-vignettes. The recommended timing of treatment initiation differed between continents for 2/9 case-vignettes (22%), in 7/9 (77.9%) comparing the Netherlands with other countries, and based on years of experience for 5/9 (56%). Conclusions: Although the response rate was limited, in asymptomatic patients with mPDAC, immediate treatment is most often preferred. Delaying treatment until symptoms occur is considered in patients with limited metastatic disease, more comorbidities, and higher age. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Dutch Pancreatitis Study Group. Endoscopic transgastric vs surgical necrosectomy for infected necrotizing pancreatitis: a randomized trial," in the 2012 issue of the journal and a response by the authors is also presented.

A letter to the editor is presented in response to an article on the drainage of sterile fluid collections in acute pancreatitis, which was published in a previous issue.

A response by H. C. Santvoort and colleagues to a letter to the editor regarding the article "Minimally Invasive Step-up Approach versus Maximal Necrosectomy in Patients with Acute Necrotizing Pancreatitis (PANTER)" in the April 22, 20109 issue is presented.

A letter to the editor is presented in response to the article "Probiotics in patients with severe acute pancreatitis: a meta-analysis," by S. Sun and colleagues, in a 2008 issue.

Previous studies have reported conflicting results of prolonged antibiotic prophylaxis on infectious complications after pancreatoduodenectomy. This study evaluated the effect of prolonged antibiotics on surgical-site infections (SSIs) after pancreatoduodenectomy. Methods: A systematic review and meta-analysis was undertaken of SSIs in patients with perioperative (within 24 h) versus prolonged antibiotic (over 24 h) prophylaxis after pancreatoduodenectomy. SSIs were classified as organ/space infections or superficial SSI within 30 days after surgery. ORs were calculated using a Mantel-Haenszel fixed-effect model. Results: Ten studies were included in the qualitative analysis, of which 8 reporting on 1170 patients were included in the quantitative analysis. The duration of prolonged antibiotic prophylaxis varied between 2 and 10 days after surgery. Four studies reporting on 782 patients showed comparable organ/space infection rates in patients receiving perioperative and prolonged antibiotics (OR 1.35, 95 per cent c.i. 0.94 to 1.93). However, among patients with preoperative biliary drainage (5 studies reporting on 577 patients), organ/space infection rates were lower with prolonged compared with perioperative antibiotics (OR 2.09, 1.43 to 3.07). Three studies (633 patients) demonstrated comparable superficial SSI rates between patients receiving perioperative versus prolonged prophylaxis (OR 1.54, 0.97 to 2.44), as well as in patients with preoperative biliary drainage in 4 studies reporting on 431 patients (OR 1.60, 0.89 to 2.88). Conclusion: Prolonged antibiotic prophylaxis is associated with fewer organ/space infection in patients who undergo preoperative biliary drainage. However, the optimal duration of antibiotic prophylaxis after pancreatoduodenectomy remains to be determined and warrants confirmation in an RCT. [ABSTRACT FROM AUTHOR]

Background: Infected necrotising pancreatitis is a potentially lethal disease and an indication for invasive intervention. The surgical step-up approach is the standard treatment. A promising alternative is the endoscopic step-up approach. We compared both approaches to see whether the endoscopic step-up approach was superior to the surgical step-up approach in terms of clinical and economic outcomes.Methods: In this multicentre, randomised, superiority trial, we recruited adult patients with infected necrotising pancreatitis and an indication for invasive intervention from 19 hospitals in the Netherlands. Patients were randomly assigned to either the endoscopic or the surgical step-up approach. The endoscopic approach consisted of endoscopic ultrasound-guided transluminal drainage followed, if necessary, by endoscopic necrosectomy. The surgical approach consisted of percutaneous catheter drainage followed, if necessary, by video-assisted retroperitoneal debridement. The primary endpoint was a composite of major complications or death during 6-month follow-up. Analyses were by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN09186711.Findings: Between Sept 20, 2011, and Jan 29, 2015, we screened 418 patients with pancreatic or extrapancreatic necrosis, of which 98 patients were enrolled and randomly assigned to the endoscopic step-up approach (n=51) or the surgical step-up approach (n=47). The primary endpoint occurred in 22 (43%) of 51 patients in the endoscopy group and in 21 (45%) of 47 patients in the surgery group (risk ratio [RR] 0·97, 95% CI 0·62-1·51; p=0·88). Mortality did not differ between groups (nine [18%] patients in the endoscopy group vs six [13%] patients in the surgery group; RR 1·38, 95% CI 0·53-3·59, p=0·50), nor did any of the major complications included in the primary endpoint.Interpretation: In patients with infected necrotising pancreatitis, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing major complications or death. The rate of pancreatic fistulas and length of hospital stay were lower in the endoscopy group. The outcome of this trial will probably result in a shift to the endoscopic step-up approach as treatment preference.Funding: The Dutch Digestive Disease Foundation, Fonds NutsOhra, and the Netherlands Organization for Health Research and Development. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "ERCP for gallstone pancreatitis" by Evan L. Fogel and Stuart Sherman in the January 9, 2014 issue.

Introduction:Impairment of the mucosal barrier plays an important role in the pathophysiology of acute pancreatitis. The myosin IXB (MYO9B) gene and the two tight-junction adaptor genes, PARD3 and MAGI2, have been linked to gastrointestinal permeability. Common variants of these genes are associated with celiac disease and inflammatory bowel disease, two other conditions in which intestinal permeability plays a role. We investigated genetic variation in MYO9B, PARD3 and MAGI2 for association with acute pancreatitis. Methods:Five single nucleotide polymorphisms (SNPs) in MYO9B, two SNPs in PARD3, and three SNPs in MAGI2 were studied in a Dutch cohort of 387 patients with acute pancreatitis and over 800 controls, and in a German cohort of 235 patients and 250 controls. Results:Association to MYO9B and PARD3 was observed in the Dutch cohort, but only one SNP in MYO9B and one in MAGI2 showed association in the German cohort (p < 0.05). Joint analysis of the combined cohorts showed that, after correcting for multiple testing, only two SNPs in MYO9B remained associated (rs7259292, p = 0.0031, odds ratio (OR) 1.94, 95% confidence interval (95% CI) 1.35-2.78; rs1545620, p = 0.0006, OR 1.33, 95% CI 1.16-1.53). SNP rs1545620 is a non-synonymous SNP previously suspected to impact on ulcerative colitis. None of the SNPs showed association to disease severity or etiology. Conclusion:Variants in MYO9B may be involved in acute pancreatitis, but we found no evidence for involvement of PARD3 or MAGI2. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Chronic pancreatitis (CP) has a negative impact on quality of life (QoL). Because CP is a chronic condition, multiple assessments of QoL are required to obtain a thorough understanding of its impact on patients. Such studies are currently lacking. This study aims to gain insight into the course and predictors of QoL in patients with CP using prospective longitudinal data from a large cohort of patients. METHODS: Post hoc analysis of consecutive patients with definite CP registered in a prospective database between 2011 and 2019 in the Netherlands. Patient and disease characteristics, nutritional status, pain severity, medication usage, pancreatic function, and pancreatic interventions were assessed from medical records and through standard follow-up questionnaires. The physical and mental component summary scales of the Short-Form 36 were used to assess physical and mental QoL at baseline and during follow-up. The course of both physical and mental QoL and their associated factors were longitudinally assessed by using generalized linear mixed models. RESULTS: Overall, 1,165 patients with definite CP were included for this analysis. During 10-year follow-up, generalized linear mixed model analyses revealed improvements in both physical (41.6-45.2, P < 0.001) and mental (45.9-46.6, P = 0.047) QoL. Younger age, current alcohol consumption, employment, no need for dietetic consultation, no steatorrhea, lower Izbicki pain score, and pain coping mechanism were positively associated with physical QoL (P < 0.05). For mental QoL, a positive correlation was found between employment, nonalcoholic CP, no need for dietetic consultation, no steatorrhea, lower Izbicki pain score, pain coping mechanism, and surgical treatment. No association was observed between disease duration and longitudinal QoL per patient. DISCUSSION: This nationwide study provides insight into the dynamics of physical and mental QoL in patients with CP over time. Important and potentially influenceable factors to improve QoL are nutritional status, exocrine pancreatic function, employment status, and patients' coping strategy. [ABSTRACT FROM AUTHOR]

Background: Cholangitis is a late complication after pancreatoduodenectomy with considerable clinical impact and is difficult to treat. The aim of this systematic review was to provide an overview of the literature identifying risk factors for postoperative cholangitis. Methods: A systematic search of the databases PUBMED and EMBASE was performed to identify all studies reporting on possible risk factors for cholangitis following pancreatoduodenectomy. Data on patient, peri- and postoperative characteristics were collected. Risk of bias assessment was done according to the methodological index for non-randomized studies (MINORS) criteria. Results: In total, 464 studies were identified. Eight studies met the inclusion criteria for this analysis. The definition of postoperative cholangitis was inconsistent, with four studies using the Tokyo Guidelines, whereas other studies used different definitions. Data on 26 potential risk factors concerning the patient, peri- and postoperative characteristics were analyzed. Five factors were significantly associated with cholangitis in two or more studies: high body mass index, duration of surgery, benign disease, postoperative pancreatic fistula, and postoperative serum alkaline phosphatase. Conclusion: Multiple potential risk factors for postoperative cholangitis were identified, with large discrepancies between studies. Prospective research, with consensus on the definition, is required to determine the true relevance of these risk factors. [ABSTRACT FROM AUTHOR]

Background: In the era of advanced surgical techniques and improved perioperative care, the willingness to perform emergency operations in elderly patients continues to increase. This systematic review aimed at assessing the clinical outcomes of early cholecystectomy in elderly patients with acute cholecystitis. Methods: Medline, Embase, and Cochrane Library databases were systematically searched for studies reporting on early cholecystectomy for acute cholecystitis in patients aged = 70 years. The conversion rate, perioperative morbidity, and mortality were calculated using a random-effects model. Results: Eight articles fell within the scope of this study. In total, 592 patients were identified. The mean age was 81 years. Early cholecystectomy was performed laparoscopically in 316 patients (53%) and open in 276 patients (47%). The procedure was associated with a conversion rate of 23% (95% CI 18.6-28.3), a perioperative morbidity of 24% (95% CI 20.5-27.5), and a mortality of 3.5% (95% CI 2.3-5.4). Conclusion: Early cholecystectomy seems to be a feasible treatment in elderly patients with acute cholecystitis. To reduce morbidity, patients who may benefit from surgery ought to be selected carefully. Future prospective studies should compare early cholecystectomy with alternative treatments to select the treatment that is most appropriate for elderly patients. [ABSTRACT FROM AUTHOR]

In this letter Marc G. Besselink responds to criticism of the article "Probiotic Prophylaxis in Predicted Severe Acute Pancreatitis: A Randomised Double-Blind Placebo Controlled Trial" published in volume 371 of this journal in 2008.

Background: Chronic pancreatitis (CP) is an inflammatory disease that may be complicated by abdominal pain, pancreatic dysfunction, nutritional deficiencies, and diminished bone density. Importantly, it is also associated with a substantially impaired quality of life and reduced life expectancy. This may partly be explained by suboptimal treatment, in particular the long-term management of this chronic condition, despite several national and international guidelines. Standardization of care through a structured implementation of guideline recommendations may improve the level of care and lower the complication rate of these patients. Therefore, the aim of the present study is to evaluate to what extent patient education and standardization of care, through the implementation of an evidence-based integrated management algorithm, improve quality of life and reduce pain severity in patients with CP. Methods: The COMBO trial is a nationwide stepped-wedge cluster-randomized controlled trial. In a stepwise manner, 26 centers, clustered in 6 health regions, cross-over from current practice to care according to an evidence-based integrated management algorithm. During the current practice phase, study participants are recruited and followed longitudinally through questionnaires. Individual patients contribute data to both study periods. Co-primary study endpoints consist of quality of life (assessed by the PANQOLI score) and level of pain (assessed by the Izbicki questionnaire). Secondary outcomes include process measure outcomes, clinical outcomes (e.g., pancreatic function, nutritional status, bone health, interventions, medication use), utilization of healthcare resources, (in) direct costs, and the level of social participation. Standard follow-up is 35 months from the start of the trial. Discussion: This is the first stepped-wedge cluster-randomized controlled trial to investigate whether an evidence-based integrated therapeutic approach improves quality of life and pain severity in patients with CP as compared with current practice. Trial registration: ISRCTN, ISRCTN13042622. Registered on 5 September 2020. [ABSTRACT FROM AUTHOR]

Objectives: To investigate national mortality trends over a 12-year period for patients with severe acute pancreatitis (SAP) admitted to Dutch ICUs. Additionally, an assessment of outcome in SAP was undertaken to differentiate between early (< 14 d of ICU admission) and late (> 14 d of ICU admission) mortality.Design: Data from the Dutch National Intensive Care Evaluation and health insurance companies' databases were extracted. Outcomes included 14-day, ICU, hospital, and 1-year mortality. Mortality before and after 2010 was compared using mixed logistic regression and mixed Cox proportional-hazards models. Sensitivity analyses, excluding early mortality, were performed to assess trends in late mortality.Setting: Not applicable.Patients: Consecutive adult patients with SAP admitted to all 81 Dutch ICUs between 2007 and 2018.Interventions: Not applicable.Measurements and Main Results: Among 4,160 patients treated in 81 ICUs, 14-day mortality was 17%, ICU mortality 17%, hospital mortality 23%, and 1-year mortality 33%. After 2010 in-hospital mortality adjusted for age, sex, modified Marshall, and Acute Physiology and Chronic Health Evaluation III scores were lower (odds ratio [OR], 0.76; 95% CI, 0.61-0.94) than before 2010. There was no change in ICU and 1-year mortality. Sensitivity analyses excluding patients with early mortality demonstrated a decreased ICU mortality (OR, 0.45; 95% CI, 0.32-0.64), decreased in-hospital (OR, 0.48; 95% CI, 0.36-0.63), and decreased 1-year mortality (hazard ratio, 0.81; 95% CI, 0.68-0.96) after 2010 compared with 2007-2010.Conclusions: Over the 12-year period examined, mortality in patients with SAP admitted to Dutch ICUs did not change, although after 2010 late mortality decreased. Novel therapies should focus on preventing early mortality in SAP. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic cancer has a poor prognosis, even in patients that can be surgically treated with curative intent. An interesting subgroup of resected pancreatic cancers are those associated with pancreatic cystic neoplasms (PCN), since overall survival might differ from pancreatic cancer not associated with PCN. Although several single-center studies published conflicting data on this topic, nationwide studies are lacking. In this nationwide, registry-based study, we aimed to compare the overall survival between patients with PCN-associated pancreatic cancers to those with pancreatic cancer not associated with PCN. We found that 12% of resected pancreatic cancers patients were PCN-associated. Overall survival was better in patients with PCN-associated pancreatic cancer as compared to those not associated with PCN. Future prospective studies should focus on the impact of these findings, such as the impact of (neo)adjuvant treatment regimens in this specific patient group. Background: Outcome after resection of pancreatic ductal adenocarcinoma associated with pancreatic cystic neoplasms (PCN-PDAC) might differ from PDAC not associated with PCN. This nationwide, registry-based study aimed to compare the overall survival (OS) in these patients. Methods: Data from consecutive patients after pancreatic resection for PDAC between 2013 and 2018 were matched with the corresponding pathology reports. Primary outcome was OS for PCN-PDAC and PDAC including 1-year and 5-year OS. Cox regression analysis was used to correct for prognostic factors (e.g., pT-stage, pN-stage, and vascular invasion). Results: In total, 1994 patients underwent resection for PDAC including 233 (12%) with PCN-PDAC. Median estimated OS was better in patients with PCN-PDAC (34.5 months [95%CI 25.6 to 43.5]) as compared to PDAC not associated with PCN (18.2 months [95%CI 17.3 to 19.2]; hazard ratio 0.53 [95%CI 0.44–0.63]; p < 0.001). The difference in OS remained after correction for prognostic factors (adjusted hazard ratio 1.58 [95%CI 1.32−1.90]; p < 0.001). Conclusions: This nationwide registry-based study showed that 12% of resected PDAC were PCN-associated. Patients with PCN-PDAC had better OS as compared to PDAC not associated with PCN. [ABSTRACT FROM AUTHOR]

Background: Acute pancreatitis is a severe condition that requires early identification of patients at risk of developing potentially lethal complications. Current clinical scoring systems and biochemical parameters are insufficient. In this study, we aimed to assess whether early plasma Angiopoietin-2 (Ang-2) is associated with adverse outcomes in patients with predicted severe acute pancreatitis (SAP). Study Design: This analysis is a substudy of the PROPATRIA trial (probiotics vs placebo in patients with predicted SAP). The Ang-2 levels were measured prospectively in plasma in the first 5 days after admission in 115 patients. Results: Early Ang-2 levels were higher in patients who developed SAP: 6.4 vs 3.1 μg/L (p < 0.001) and also were higher in patients who developed multiorgan failure in the first week (p = 0.001) and after the first week (p = 0.049). Furthermore, high Ang-2 levels were associated with infectious complications in the first week (p < 0.001) and after the first week (p < 0.001). Finally, plasma Ang-2 was significantly higher in patients who died (p < 0.001) and in patients who developed bowel ischemia (p < 0.001). As a predictor of adverse outcomes, plasma Ang-2 was superior to a number of current scores, such as the APACHE II score, the Imrie score, C-reactive protein, lipopolysaccharide binding protein, and procalcitonin. Conclusions: In the setting of this randomized controlled trial, early plasma Ang-2 was found to be an accurate predictor of SAP, multiorgan failure, and infectious complications. As a biomarker, it did outperform all of the investigated conventional predictors that are currently used in clinical practice. [Copyright &y& Elsevier]

Background: Surgery is the most effective treatment in patients with painful chronic pancreatitis and a dilated pancreatic duct. Studies reporting the outcomes of selected surgical approach according to the pancreatic head size in these patients are lacking. Method: This was a retrospective, observational single-centre study of consecutive patients who underwent either a Frey procedure or extended lateral pancreaticojejunostomy (eLPJ) for pain due to chronic pancreatitis with a dilated main pancreatic duct (5mm or more) between 2006 and 2017. A Frey procedure was used in patients with pancreatic head enlargement (40mm or more) and eLPJ (full-length pancreaticojejunostomy, including transection of the gastroduodenal artery) in others. A biliodigestive bypass was added in the case of biliary obstruction. Results: Overall, 140 of 220 patients met the eligibility criteria: 70 underwent a Frey procedure and 70 an eLPJ. Hepaticojejunostomy was added in 17.1 per cent of patients (Frey: 24.3 per cent; eLPJ: 10.0 per cent (P=0.025)). Major morbidity occurred in 15.0 per cent of patients (Frey: 21.4 per cent; eLPJ: 8.6 per cent (P=0.033)). After a median 7.8 years of follow-up, the mean (s.d.) decrease in Izbicki pain score was 33 (27) points (34 (28) points after a Frey procedure; 32 (26) points after an eLPJ). Pain relief was reported as 'very much' by 87.5 per cent of patients (Frey: 86.1 per cent; eLPJ: 88.9 per cent) and as 'partial' by 11.1 per cent (Frey: 13.8 per cent; eLPJ: 8.3 per cent). Conclusion: Selective-use of either a Frey procedure or eLPJ in patients with symptomatic chronic pancreatitis was-associated with low morbidity and long-term pain relief. Adding a-biliodigestive bypass did not increase morbidity. [ABSTRACT FROM AUTHOR]

Complementary to percutaneous intra-abdominal drainage, percutaneous transhepatic biliary drainage (PTBD) might ameliorate healing of pancreatic fistula and biliary leakage after pancreatoduodenectomy by diversion of bile from the site of leakage. This study evaluated technical and clinical outcomes of PTBD for this indication. All patients undergoing PTBD for leakage after pancreatoduodenectomy were retrospectively evaluated in two tertiary pancreatic centers (2014–2019). Technical success was defined as external biliary drainage. Clinical success was defined as discharge with a resolved leak, without additional surgical interventions for anastomotic leakage other than percutaneous intra-abdominal drainage. Following 822 pancreatoduodenectomies, 65 patients (8%) underwent PTBD. Indications were leakage of the pancreaticojejunostomy (n = 25; 38%), hepaticojejunostomy (n = 15; 23%) and of both (n = 25; 38%). PTBD was technically successful in 64 patients (98%) with drain revision in 40 patients (63%). Clinical success occurred in 60 patients (94%). Leakage resolved after median 33 days (IQR 21–60). PTBD related complications occurred in 23 patients (35%), including cholangitis (n = 14; 21%), hemobilia (n = 7; 11%) and PTBD related bleeding requiring re-intervention (n = 4; 6%). In hospital mortality was 3% (n = 2). Although drain revisions and complications are common, PTBD is highly feasible and appears to be effective in the treatment of biliopancreatic leakage after pancreatoduodenectomy. [ABSTRACT FROM AUTHOR]

Background: Guidelines recommending antibiotic prophylaxis at emergency cholecystectomy for cholecystitis were based on low-quality evidence. The aim of this trial was to demonstrate that omitting antibiotics is not inferior to their prophylactic use. Methods: This multicentre, randomized, open-label, non-inferiority clinical trial randomly assigned adults with mild-to-moderate acute calculous cholecystitis (immediate cholecystectomy indicated) to 2 g cefazolin administered before incision or no antibiotic prophylaxis. The primary endpoint was a composite of all postoperative infectious complications in the first 30 days after surgery. Secondary endpoints included all individual components of the primary endpoint, other morbidity, and duration of hospital stay. Results: Sixteen of 226 patients (7.1 per cent) in the single-dose prophylaxis group and 29 of 231 (12.6 per cent) in the no-prophylaxis group developed postoperative infectious complications (absolute difference 5.5 (95 per cent c.i. -0.4 to 11.3) per cent). With a noninferiority margin of 10 per cent, non-inferiority of no prophylaxis was not proven. The number of surgical-site infections was significantly higher in the no-prophylaxis group (5.3 versus 12.1 per cent; P=0.010). No differences were observed in the number of other complications, or duration of hospital stay. Conclusion: Omitting antibiotic prophylaxis is not recommended. [ABSTRACT FROM AUTHOR]

The diagnosis of pancreatic ductal adenocarcinoma (PDAC) has an enormous impact on patients, and even more so if they are of younger age. It is unclear how their treatment and outcome compare to older patients. This study compares clinicopathological characteristics and overall survival (OS) of PDAC patients aged <60 years to older PDAC patients. This is a retrospective, population-based cohort study using Netherlands Cancer Registry data of patients diagnosed with PDAC (1 January 2015–31 December 2018). Kaplan–Meier curves and Cox proportional hazards models were used to assess OS. Overall, 10,298 patients were included, of whom 1551 (15%) were <60 years. Patients <60 years were more often male, had better performance status, less comorbidities and less stage I disease, and more often received anticancer treatment (67 vs. 33%, p < 0.001) than older patients. Patients <60 years underwent resection of the tumour more often (22 vs. 14%p < 0.001), more often received chemotherapy, and had a better median OS (6.9 vs. 3.3 months, p < 0.001) compared to older patients. No differences in median OS were demonstrated between both age groups of patients who underwent resection (19.7 vs. 19.4 months, p = 0.123), received chemotherapy alone (7.8 vs. 8.5 months, p = 0.191), or received no anticancer treatment (1.8 vs. 1.9 months, p = 0.600). Patients <60 years with stage-IV disease receiving chemotherapy had a somewhat better OS (7.5 vs. 6.3 months, p = 0.026). Patients with PDAC <60 years more often underwent resection despite less stage I disease and had superior OS. Stratified for treatment, however, survival was largely similar. [ABSTRACT FROM AUTHOR]

Neoadjuvant therapy may improve survival compared with upfront surgery in patients with resectable and borderline resectable pancreatic cancer, but high-quality evidence is lacking. We systematically searched for randomised trials comparing neoadjuvant therapy with upfront surgery for resectable and borderline resectable pancreatic cancer published since database inception until December 2020. The primary outcome was overall survival (OS) by intention-to-treat with subgroup analyses for resectability status. Meta-analyses using a random-effects model were performed. Certainty of evidence was assessed using the GRADE approach. Seven trials with 938 patients were included. All trials included a neoadjuvant gemcitabine-based chemo(radio)therapy arm. None of the studies used adjuvant FOLFIRINOX. Neoadjuvant therapy improved OS (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.52–0.85; P = 0.001; I 2 = 46%) compared with upfront surgery. This represents an increase in median OS from 19 to 29 months. In the subgroup of resectable pancreatic cancer (i.e., venous contact ≤180°, no arterial contact), no statistically significant difference in OS was observed (HR 0.77, 95% CI 0.53–1.12; P = 0.18; I 2 = 20%). In the subgroup of borderline resectable pancreatic cancer (i.e. venous contact >180°, any arterial contact), neoadjuvant therapy improved OS (HR 0.61, 95% CI 0.44–0.85; P = 0.004; I 2 = 59%). The GRADE certainty of evidence was high for the outcome of OS. Neoadjuvant therapy improves OS compared with upfront surgery in patients with borderline resectable pancreatic cancer. More evidence is required on whether neoadjuvant therapy improves survival for patients with resectable pancreatic cancer. • Neoadjuvant therapy was superior for borderline resectable pancreatic cancer. • For patients with resectable pancreatic cancer, no difference was demonstrated. • More evidence is required for patients with resectable pancreatic cancer. • A limitation of the study is the use of gemcitabine-based adjuvant regimens. [ABSTRACT FROM AUTHOR]

Background: Venous resection of the superior mesenteric or portal vein is increasingly performed in pancreatic cancer surgery, whereas results of studies on short- and long-term outcomes are contradictory. The aim of this study was to evaluate the impact of the type of venous resection in pancreatoduodenectomy for pancreatic cancer on postoperative morbidity and overall survival. Methods: This nationwide retrospective cohort study included all patients who underwent pancreatoduodenectomy for pancreatic cancer in 18 centres (2013-2017). Results: A total of 1311 patients were included, of whom 17 per cent underwent wedge resection and 10 per cent segmental resection. Patients with segmental resection had higher rates of major morbidity (39 versus 20 versus 23 per cent, respectively; P<0.001) and portal or superior mesenteric vein thrombosis (18 versus 5 versus 1 per cent, respectively; P<0.001) and worse overall survival (median 12 versus 16 versus 20months, respectively; P<0.001), compared to patients with wedge resection and those without venous resection. Multivariable analysis showed patients with segmental resection, but not those who had wedge resection, had higher rates of major morbidity (odds ratio=1.93, 95 per cent c.i. 1.20 to 3.11) and worse overall survival (hazard ratio=1.40, 95 per cent c.i. 1.10 to 1.78), compared to patients without venous resection. Among patients who received neoadjuvant therapy, there was no difference in overall survival among patients with segmental and wedge resection and those without venous resection (median 32 versus 25 versus 33months, respectively; P=0.470), although there was a difference in majormorbidity rates (52 versus 19 versus 21 per cent, respectively; P =0.012). Conclusion: In pancreatic surgery, the short- and long-term outcomes are worse in patients with venous segmental resection, compared to patients with wedge resection and those without venous resection. [ABSTRACT FROM AUTHOR]

Introduction of online adaptive MR-guided radiotherapy enables stereotactic body radiation therapy (SBRT) of upper abdominal tumors. This study aimed to evaluate the feasibility of MR-guided SBRT on a 1.5 T MR-linac in patients with unresectable upper abdominal malignancies. Patients treated at the UMC Utrecht (April 2019 to December 2020) were identified in the prospective 'Multi-OutcoMe EvaluatioN of radiation Therapy Using the MR-linac' (MOMENTUM) study. Feasibility of treatment was arbitrarily defined as an on-table time interval of ≤60 min for >75% of delivered fractions and completion of >95% of fractions as scheduled, reflecting patient tolerability. Acute treatment-related toxicity was assessed at 3 months of follow-up and graded according to the National Cancer Institute Common Terminology Criteria of Adverse Events version 5.0. Twenty-five consecutive patients with a median follow-up time of 8 (range 4–23) months were treated with 35 Gray (n = 4) and 40 Gray (n = 21) in five fractions over 2 weeks. For all fractions, contours were adapted based on the daily anatomy and delivered within 47 min/fraction (range 30–74). In 98/117 fractions (84%), adapted treatment was completed within 1 h. All patients received the scheduled irradiation dose as planned. No acute grade 3 toxicity or higher was reported. Treatment resulted in pain alleviation in 11/13 patients. Online adaptive MR-guided SBRT on a 1.5 T MR-linac is feasible and well-tolerated in patients with unresectable upper abdominal malignancies. Dose escalation studies, followed by comparative studies, are needed to determine the optimal radiation dose for irradiation of upper abdominal malignancies. [ABSTRACT FROM AUTHOR]

Data regarding long-term quality of life and exocrine and endocrine insufficiency after pancreatic surgery for premalignant and benign (non-pancreatitis) disease are lacking. This cross-sectional study included patients ≥3 years after pancreatoduodenectomy or left pancreatectomy in six Dutch centers (2006–2016). Outcomes were measured with the EQ-5D-5L, the EORTC QLQ-C30, an exocrine and endocrine pancreatic insufficiency questionnaire, and PAID20. Questionnaires were completed by 153/183 patients (response rate 84%, median follow-up 6.3 years). Surgery related complaints were reported by 72/153 patients (47%) and 13 patients (8.4%) would not undergo this procedure again. The VAS (EQ-5D-5L) was 76 ± 17 versus 82 ± 0.4 in the general population (p < 0.001). The mean global health status (QLQ-C30) was 78 ± 17 versus 78 ± 17, p = 1.000. Fatigue, insomnia, and diarrhea were clinically relevantly worse in patients. Exocrine pancreatic insufficiency was reported by 62 patients (41%) with relieve of symptoms by enzyme supplementation in 48%. New-onset diabetes mellitus was present in 22 patients (14%). The median PAID20 score was 6.9/20 (IQR 2.5–17.8). Although generic quality of life after pancreatic resection for pre-malignant and benign disease was similar to the general population and diabetes-related distress was low, almost half suffered from a range of symptoms highlighting the need for long-term counseling. [ABSTRACT FROM AUTHOR]

Aim: Unlike meta‐analyses of randomized controlled trials, population‐based studies in colorectal cancer (CRC) patients have shown a significant association between open surgery and increased 30‐ and 90‐day mortality compared with laparoscopic surgery. Long‐term mortality, however, is scarcely reported. This retrospective population‐based study aimed to compare long‐term mortality after open and laparoscopic surgery for CRC. Method: The Dutch Colorectal Audit and the Dutch Cancer Centre registry were used to identify patients from three large nonacademic teaching hospitals who underwent curative resection for CRC between 2009 and 2018. Patients with relative contraindications for laparoscopic surgery (cT4 or pT4 tumours, distant metastasis requiring additional resection and emergency surgery) were excluded. Multivariable regression was used to assess the effect of laparoscopic surgery on long‐term mortality with adjustment for gender, age, American Society of Anesthesiologists score, TNM stage, chemoradiation therapy and other confounders. Results: We included 4531 patients, of whom 1298 (29%) underwent open surgery. The median follow‐up was 43 months (interquartile range 23–71 months). Open surgery was associated with an increased risk of long‐term mortality (adjusted hazard ratio 1.26, 95% confidence interval 1.10–1.45, p = 0.001). Mixed‐effects Cox regression with year of surgery as a random effect also showed an increased risk after open surgery (adjusted hazard ratio 1.33, 95% confidence interval 1.11–1.52, p = 0.004). Conclusion: Open surgery seems to be associated with increased long‐term mortality in the elective setting for CRC patients. A minimally invasive approach might improve long‐term outcomes. [ABSTRACT FROM AUTHOR]

In pancreatoduodenectomy specimens, dissection method may affect the assessment of primary tumour origin (i.e. pancreatic, distal bile duct or ampullary adenocarcinoma), which is primarily determined macroscopically. This is the first study to prospectively compare the two commonly used techniques, i.e. axial slicing and bivalving. In four centres, a randomized controlled trial was performed in specimens of patients with a suspected (pre)malignant tumour in the pancreatic head. Primary outcome measure was the level of certainty (scale 0–100) regarding tumour origin by four independent gastrointestinal pathologists based on macroscopic assessment. Secondary outcomes were inter-observer agreement and R1 rate. In total, 128 pancreatoduodenectomy specimens were randomized. The level of certainty in determining the primary tumour origin did not differ between axial slicing and bivalving (mean score 72 [sd 13] vs. 68 [sd 16], p = 0.21), nor did inter-observer agreement, both being moderate (kappa 0.45 vs. 0.47). In pancreatic cancer specimens, R1 rate (60% vs. 55%, p = 0.71) and the number of harvested lymph nodes (median 16 vs. 17, p = 0.58) were similar. This study demonstrated no differences in determining the tumour origin between axial slicing and bivalving. Both techniques performed similarly regarding inter-observer agreement, R1 rate, and lymph node harvest. [ABSTRACT FROM AUTHOR]

Pancreatic duct disruption or disconnection is a potentially severe complication of necrotizing pancreatitis. With no existing treatment guidelines, it is unclear whether there is any consensus among experts in clinical practice. We evaluated current expert opinion regarding the diagnosis and treatment of pancreatic duct disruption and disconnection in an international case vignette study. An online case vignette survey was sent to 110 international expert pancreatologists. Expert selection was based on publications in the last 5 years and/or participation in development of IAP/APA and ESGE guidelines on acute pancreatitis. Consensus was defined as agreement by at least 75% of the experts. The response rate was 51% (n = 56). Forty-four experts (79%) obtained a MRI/MRCP and 52 experts (93%) measured amylase levels in percutaneous drain fluid to evaluate pancreatic duct integrity. The majority of experts favored endoscopic transluminal drainage for infected (peri)pancreatic necrosis and pancreatic duct disruption (84%, n = 45) or disconnection (88%, n = 43). Consensus was lacking regarding the treatment of patients with persistent percutaneous drain production, and with persistent sterile necrosis. This international survey of experts demonstrates that there are many areas for which no consensus existed, providing clear focus for future investigation. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine pancreatic surgery specific short- and long-term complications of pediatric, adolescent and young adult (PAYA) patients who underwent pancreatic resection, as compared to a comparator cohort of adults. A nationwide retrospective cohort study was performed in PAYA patients who underwent pancreatic resection between 2007 and 2016. PAYA was defined as all patients <40 years at time of surgery. Pancreatic surgery-specific complications were assessed according to international definitions and textbook outcome was determined. A total of 230 patients were included in the PAYA cohort (112 distal pancreatectomies, 99 pancreatoduodenectomies), and 2526 patients in the comparator cohort. For pancreatoduodenectomy, severe morbidity (29.3% vs. 28.6%; P = 0.881), in-hospital mortality (1% vs. 4%; P = 0.179) and textbook outcome (62% vs. 58%; P = 0.572) were comparable between the PAYA and the comparator cohort. These outcomes were also similar for distal pancreatectomy. After pancreatoduodenectomy, new-onset diabetes mellitus (8% vs. 16%) and exocrine pancreatic insufficiency (27% vs. 73%) were lower in the PAYA cohort when compared to adult literature. Pancreatic surgery-specific complications were comparable with patients ≥40 years. Development of endocrine and exocrine insufficiency in PAYA patients who underwent pancreatoduodenectomy, however, was substantially lower compared to adult literature. [ABSTRACT FROM AUTHOR]

Background: Severe pancreatitis may result in a disrupted pancreatic duct, which is associated with a complicated clinical course. Diagnosis of a disrupted pancreatic duct is not standardized in clinical practice or international guidelines. We performed a systematic review of the literature on imaging modalities for diagnosing a disrupted pancreatic duct in patients with acute pancreatitis. Methods: A systematic search was performed in PubMed, Embase and Cochrane library databases to identify all studies evaluating diagnostic modalities for the diagnosis of a disrupted pancreatic duct in acute pancreatitis. All data regarding diagnostic accuracy were extracted. Results: We included 8 studies, evaluating five different diagnostic modalities in 142 patients with severe acute pancreatitis. Study quality was assessed, with proportionally divided high and low risk of bias and low applicability concerns in 75% of the studies. A sensitivity of 100% was reported for endoscopic ultrasound and endoscopic retrograde cholangiopancreatography. The sensitivity of magnetic resonance cholangiopancreatography with or without secretin was 83%. A sensitivity of 92% was demonstrated for a combined cohort of secretin-magnetic resonance cholangiopancreatography and magnetic resonance cholangiopancreatography. A sensitivity of 100% and specificity of 50% was found for amylase measurements in drain fluid compared with ERCP. Conclusions: This review suggests that various diagnostic modalities are accurate in diagnosing a disrupted pancreatic duct in patients with acute pancreatitis. Amylase measurement in drain fluid should be standardized. Given the invasive nature of other modalities, secretin-magnetic resonance cholangiopancreatography or magnetic resonance cholangiopancreatography would be recommended as first diagnostic modality. Further prospective studies, however, are needed. [ABSTRACT FROM AUTHOR]