Impairment of perioperative activities of daily living is associated with poor prognosis following pancreatectomy for pancreatic cancer.

PURPOSE: It has reported that the prevalence of frailty in patients with pancreatic cancer is 45%. The number of patients with pancreatic cancer is increasing, and within this cohort, patients often suffer from impaired activities of daily living (ADLs). This study aimed to examine the association between perioperative Barthel Index (BI) scores, a validated measure of ADLs, and survival outcomes after pancreatectomy for pancreatic cancer. METHODS: We analyzed the data of 201 patients who underwent pancreatectomy for pancreatic cancer between 2010 and 2020. Preoperative and postoperative ADLs were assessed using the BI (range: 0-100; higher scores indicated greater independence). A preoperative or postoperative BI score ≤ 85 was defined as an impairment of perioperative ADLs. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) after adjusting for potential confounders. RESULTS: Among the 201 patients, 14 (7.0%) had a preoperative BI score ≤ 85 and 50 (25%) had a postoperative BI score ≤ 85. Impairment of perioperative ADLs was independently associated with shorter overall survival (multivariable HR: 2.66, 95% confidence interval [95%CI]: 1.75-4.03, P < 0.001), cancer-specific survival (multivariable HR: 2.64, 95%CI: 1.15-4.25, P < 0.001), and recurrence-free survival (multivariable HR: 1.94, 95%CI: 1.08-3.50, P = 0.021). CONCLUSION: Impairment of perioperative ADLs is associated with poor prognosis following pancreatectomy for pancreatic cancer. The maintenance and improvement of perioperative ADLs could play an important role in providing favorable long-term outcomes in patients with pancreatic cancer.

Drainage and irrigation on demand may decrease severe septic complications and mortality in pancreatic resections.

PURPOSE: The necessity of routine drain placement in pancreatic resections is controversial. Some randomized controlled trials have shown that the omission of drainage is safe for some patients, whereas reintervention rates and mortality rates are substantial for others. The present study aimed to assess fistula-associated outcomes in the setting of routine drain placement and drain irrigation on demand. METHODS: Between 01/2017 and 12/2022, perioperative and outcome data from patients who underwent consecutive pancreatoduodenectomies (PD, n = 253) or distal pancreatectomies (DP, n = 72) were prospectively collected in the electronic StuDoQ database and analysed. All patients underwent intraoperative drain placement. Drains were removed starting at postoperative day 2 in PD or at day 5 in DP after testing for amylase concentration. In case of high amylase levels or macroscopically suspicious pancreatic fistulas, drain irrigation was started. Nondrained fluid collections underwent percutaneous radiologic or transluminal endoscopic evacuation. RESULTS: Clinically relevant pancreatic fistulas were detected in 53 of 325 patients (POPF grade B 16.3%, grade C 1.2%). 43.3% of those had drain irrigation. Additional interventional or endoscopic drainage was necessary in 14 and 5 patients, respectively (overall 5.8%), and were observed in 4.0% of patients with PD and in 12.5% with DP (p = 0.009). Delayed fistula-associated postpancreatectomy haemorrhage (PPH) was present in 1.2% (4/325) of patients. The fistula- and delayed PPH-associated reoperation rate was 1.5% (5/325). The 30-day and in-hospital mortality rates were both 1.5% (5/325), and the rate of fistula-associated mortality was 0.6% (2/325). The overall 90-day mortality rate was 4.5%. CONCLUSIONS: In pancreatectomies, a standardized drainage protocol including on-demand drain irrigation results in very low fistula-associated morbidity and mortality and an infrequent need for interventional or surgical reintervention as compared to previously published drainage studies.

Impact on survival of sarcopenia, systemic inflammatory response and anthropometric factors after pancreatectomy for resectable pancreatic adenocarcinoma.

INTRODUCTION: Pancreatic adenocarcinoma (PDAC) is becoming a public health issue with a 5-years survival rate around 10%. Patients with PDAC are often sarcopenic, which impacts postoperative outcome. At the same time, overweight population is increasing and adipose tissue promotes tumor related-inflammation. With several studies supporting independently these data, we aimed to assess if they held an impact on survival when combined. METHODS: We included 232 patients from two university hospitals (CHU de Lille, Institut Paoli Calmette), from January 2011 to December 2018, who underwent Pancreaticoduodenectomy (PD) for resectable PDAC. Preoperative CT scan was used to measure sarcopenia and visceral fat according to international cut-offs. Neutrophil to lymphocyte (NLR) and platelet to lymphocyte ratios (PLR) were used to measure inflammation. For univariate and multivariate analyses, the Cox proportional-hazard model was used. P-values below 0.05 were considered significant. RESULTS: Sarcopenic patients with visceral obesity were less likely to survive than the others in multivariate analysis (OS, HR 1.65, p= 0.043). Cutaneous obesity did not influence survival. We also observed an influence on survival when we studied sarcopenia with visceral obesity (OS, p= 0.056; PFS, p = 0.014), sarcopenia with cutaneous obesity (PFS, p= 0.005) and sarcopenia with PLR (PFS, p= 0.043). This poor prognosis was also found in sarcopenic obese patients with high PLR (OS, p= 0.05; PFS, p= 0.01). CONCLUSION: Sarcopenic obesity was associated with poor prognosis after PD for PDAC, especially in patients with systemic inflammation. Pre operative management of these factors should be addressed in pancreatic cancer patients.

Utility of ligamentum teres hepatis flap reinforcement to prevent postoperative pancreatic fistulas in robotic distal pancreatectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) is a significant contributor to morbidity and mortality after robotic distal pancreatectomy (RDP). Ligamentum teres hepatis (LTH) reinforcement of the pancreatic remnant may reduce the incidence of POPF. METHODS: Patients ≥18 years old, who underwent RDP at the University of Massachusetts Memorial Medical Center from 01/01/2018-08/31/2022. Primary endpoint was POPF incidence. Secondary outcomes included peri- and postoperative variables. RESULTS: Thirty-three patients underwent RDP, of which LTH reinforcement was used in 21 (64 â€‹%) cases. Six (18 â€‹%) patients developed a POPF. No association was identified between LTH flap reinforcement and POPF (OR 1.18, 95 â€‹% CI 0.18 to 7.85, p â€‹= â€‹0.87). There were no peri- or postoperative complications related to ligamentum teres flap creation. CONCLUSIONS: LTH reinforcement of the pancreatic remnant can be safely performed during RDP. Further studies are needed to assess the utility of this intervention to mitigate the risk of pancreatic fistula formation following RDP.

Comparative Analysis of Complications Following Distal Resections for Neuroendocrine Tumors and Adenocarcinoma: Unveiling the Differences.

BACKGROUND Adenocarcinomas and pancreatic neuroendocrine tumors (pNETs) display some similarities and differences. The aim of this study was to compare preoperative data and morphological parameters, and to assess postoperative complications after resection. MATERIAL AND METHODS Data of 162 patients who underwent distal pancreatic resection for neuroendocrine or adenocarcinoma tumor were retrospectively analyzed. After applying inclusion and exclusion criteria, 131 patients were included in the study. The preoperative data analyzed included age, sex, and ASA-PS (American Society of Anesthesiologists Physical Status) grade. The diameter of the pancreatic duct and the texture of the pancreas were analyzed. Postoperative data included grading (G1-G3), the presence of PanIN (pancreatic intraepithelial neoplasia), infiltration of structures, and postoperative complications. RESULTS Patients with adenocarcinoma were statistically older and had a higher ASA-PS class than patients with NET (P<0.001). Statistically significantly more patients with adenocarcinoma had a histopathological diagnosis of G3 (p<0.001). In patients with adenocarcinomas infiltration of structures occurred more frequently. Pancreatic duct diameter ≥3 mm was more common in patients with adenocarcinoma (P=0.045). Clinically significant pancreatic fistulas were more frequent in patients with neuroendocrine tumors (P=0.044). CONCLUSIONS Adenocarcinomas in the pancreatic body and tail are more aggressive, they cause more frequent infiltration of structures, and more often metastasize to lymph nodes compared to NETs. NETs tend to have softer pancreatic texture and higher incidence of clinically significant pancreatic fistulas, but postoperative complications of Clavien-Dindo grade ≥III occur at a similar rate in both groups.

Partial pancreatoduodenectomy versus total pancreatectomy in patients with preoperative diabetes mellitus: Comparison of surgical outcomes and quality of life.

PURPOSE: To reduce perioperative risks among patients with a preoperative diabetes mellitus (DM) a total pancreatectomy (TP) might be a alternative to pancreatoduodenectomy (PD). This study aimed to compare the postoperative quality of life (QoL) of patients with preoperative DM undergoing PD or TP. METHODS: A single-centre retrospective study was conducted, all consecutive patients with preoperative DM undergoing PD or TP between 2011 and 2023 were identified in a prospective database. The primary endpoint was QoL, prospectively assessed using EORTC QLQ-C30 questionnaires at 3, 6, and 12 months after surgery and then annually until death. Secondary endpoints were morbidity and mortality. RESULTS: Seventy-one patients were included, 17 after TP and 54 after PD. Insulin-dependent DM occurred in 21 (39%) of the PD patients. QoL was worse after TP, especially in terms of physical functioning (-31.7 points; 95% CI: -50.0 to -13.3; P < 0.001), role functioning (-41.3 points; 95% CI: -61.3 to -21.3; P < 0.001), emotional functioning (-27.5 points; 95% CI: -50.4 to -4.6; P = 0.019), fatigue symptoms (20 points; 95% CI: 2.7 to 37.4; P = 0.024) and pain symptoms (30.2 points; 95% CI: 4.1 to 56.3; P = 0.024). The rates of postoperative major complications (29% vs. 35%; P = 0.853) and mortality (11% vs. 7%; P = 0.857) were similar between TP and PD. CONCLUSION: Postoperative morbidity and mortality were comparable between PD and TP, however QoL is significantly lower after TP. Importantly, patients with preoperative DM have a 60% chance of remaining noninsulin-dependent after PD.

Early Drain Removal Versus Routine Drain Removal After Pancreaticoduodenectomy and/or Distal Pancreatectomy: A Meta-Analysis and Systematic Review.

BACKGROUND: Early drain removal (EDR) has been widely accepted, but not been routinely used in patients after pancreaticoduodenectomy (PD) and distal pancreatectomy (DP). This study aimed to evaluate the safety and benefits of EDR versus routine drain removal (RDR) after PD or DP. METHODS: A systematic search was conducted on medical search engines from January 1, 2008 to November 1, 2023, for articles that compared EDR versus RDR after PD or DP. The primary outcome was clinically relevant postoperative pancreatic fistula (CR-POPF). Further analysis of studies including patients with low-drain fluid amylase (low-DFA) on postoperative day 1 and defining EDR timing as within 3 days was also performed. RESULTS: Four randomized controlled trials (RCTs) and eleven non-RCTs with a total of 9465 patients were included in this analysis. For the primary outcome, the EDR group had a significantly lower rate of CR-POPF (OR 0.23; p < 0.001). For the secondary outcomes, a lower incidence was observed in delayed gastric emptying (OR 0.63, p = 0.02), Clavien-Dindo III-V complications (OR 0.48, p < 0.001), postoperative hemorrhage (OR 0.55, p = 0.02), reoperation (OR 0.57, p < 0.001), readmission (OR 0.70, p = 0.003) and length of stay (MD -2.04, p < 0.001) in EDR. Consistent outcomes were observed in the subgroup analysis of low-DFA patients and definite EDR timing, except for postoperative hemorrhage in EDR. CONCLUSION: EDR after PD or DP is beneficial and safe, reducing the incidence of CR-POPF and other postoperative complications. Further prospective studies and RCTs are required to validate this finding.

The Potential Clinical Benefits of Direct Surgical Transgastric Pancreatic Necrosectomy for Patients With Infected Necrotizing Pancreatitis.

OBJECTIVE: Surgical transgastric pancreatic necrosectomy (STGN) has the potential to overcome the shortcomings (ie, repeat interventions, prolonged hospitalization) of the step-up approach for infected necrotizing pancreatitis. We aimed to determine the outcomes of STGN for infected necrotizing pancreatitis. MATERIALS AND METHODS: This observational cohort study included adult patients who underwent STGN for infected necrosis at two centers from 2008 to 2022. Patients with a procedure for pancreatic necrosis before STGN were excluded. Primary outcomes included mortality, length of hospital and intensive care unit (ICU) stay, new-onset organ failure, repeat interventions, pancreatic fistulas, readmissions, and time to episode closure. RESULTS: Forty-three patients underwent STGN at a median of 48 days (interquartile range [IQR] 32-70) after disease onset. Mortality rate was 7% (n = 3). After STGN, the median length of hospital was 8 days (IQR 6-17), 23 patients (53.5%) required ICU admission (2 days [IQR 1-7]), and new-onset organ failure occurred in 8 patients (18.6%). Three patients (7%) required a reintervention, 1 (2.3%) developed a pancreatic fistula, and 11 (25.6%) were readmitted. The median time to episode closure was 11 days (IQR 6-22). CONCLUSIONS: STGN allows for treatment of retrogastric infected necrosis in one procedure and with rapid episode resolution. With these advantages and few pancreatic fistulas, direct STGN challenges the step-up approach.

Evaluation of pancreatic morphometric parameters, exocrine function, and nutritional status and their causal relationships in long-term survivors following pancreatectomy.

BACKGROUND: Patients undergoing pancreatectomy are at risk for pancreatic exocrine insufficiency and malnutrition. However, the incidence of these complications and the associated risk factors have not been sufficiently examined. This study aimed to investigate the changes in pancreatic morphology, pancreatic exocrine function, and long-term nutritional status after pancreatectomy. METHODS: We assessed the nutritional status, pancreatic morphologic parameters, and pancreatic exocrine function in patients undergoing pancreaticoduodenectomy and distal pancreatectomy. Nutritional status was evaluated on the basis of body weight change, body mass index, and skeletal muscle mass. Pancreatic parenchymal texture at the time of surgery, remnant volume of the pancreatic parenchyma, and diameter of the pancreatic duct were measured. Exocrine function was measured using the N-benzoyl-L-tyrosyl-p-aminobenzoic acid excretion test and the clinical signs of steatorrhea and nonalcoholic steatohepatitis. We then investigated potential causal relationships. RESULTS: Seventy patients were included in the study. Moderate and severe malnutrition were diagnosed in 19 (27%) and 15 patients (21%), respectively. Most patients with malnutrition before surgery were also found to be malnourished postoperatively. Body weight and skeletal muscle mass decreased after pancreatectomy in most patients, even in the longer term. Subclinical and clinical pancreatic exocrine insufficiency was found in 36 (51%) and 25 patients (36%), respectively, and pancreatic ductal adenocarcinoma, pancreaticoduodenectomy, dilated pancreatic duct, low preoperative body mass index, and pancreatic exocrine insufficiency grade were found to contribute to postoperative malnutrition. CONCLUSION: Pancreatic ductal adenocarcinoma, dilated pancreatic duct, pancreaticoduodenectomy, low preoperative body mass index, and pancreatic exocrine insufficiency were risk factors for postoperative malnutrition.

International differences in the selection and outcome of minimally invasive and open distal pancreatectomy: A transatlantic analysis.

BACKGROUND: The efficacy and safety of minimally invasive distal pancreatectomy have been confirmed by randomized trials, but current patient selection and outcome of minimally invasive distal pancreatectomy in large international cohorts is unknown. This study aimed to compare the use and outcome of minimally invasive distal pancreatectomy in North America, the Netherlands, Germany, and Sweden. METHODS: All patients in the 4 Global Audits on Pancreatic Surgery Group (GAPASURG) registries who underwent minimally invasive distal pancreatectomy or open distal pancreatectomy during 2014-2020 were included. RESULTS: Overall, 20,158 distal pancreatectomies were included, of which 7,316 (36%) were minimally invasive distal pancreatectomies. Use of minimally invasive distal pancreatectomy varied from 29% to 54% among registries, of which 13% to 35% were performed robotically. Both the use of minimally invasive distal pancreatectomy and robotic surgery were the highest in the Netherlands. Patients undergoing minimally invasive distal pancreatectomy tended to have a younger age (Germany and Sweden), female sex (North America, Germany), higher body mass index (North America, the Netherlands, Germany), lower comorbidity classification (North America, Germany, Sweden), lower performance status (Germany), and lower rate of pancreatic adenocarcinoma (all). The minimally invasive distal pancreatectomy group had fewer vascular resections (all) and lower rates of severe complications and mortality (North America, Germany). In the multivariable regression analysis, country was associated with severe complications but not with 30-day mortality. Minimally invasive distal pancreatectomy was associated with a lower risk of 30-day mortality compared with open distal pancreatectomy (odds ratio 1.633, 95% CI 1.159-2.300, P = .005). CONCLUSIONS: Considerable disparities were seen in the use of minimally invasive distal pancreatectomy among 4 transatlantic registries of pancreatic surgery. Overall, minimally invasive distal pancreatectomy was associated with decreased mortality as compared with open distal pancreatectomy. Differences in patient selection among countries could imply that countries are in different stages of the learning curve.

Efficacy of Reinforced Stapler for Preventing Postoperative Pancreatic Fistula After Minimally Invasive Distal Pancreatectomy.

BACKGROUND/AIM: Although minimally invasive distal pancreatectomy (MIDP) has become a treatment option for benign and malignant pancreatic tumors, the safety and efficacy of reinforced staplers in MIDP remain controversial. The present study was performed to evaluate the safety of reinforced staplers in MIDP and identify the risk factors for postoperative pancreatic fistula (POPF) after MIDP with reinforced staplers. PATIENTS AND METHODS: In total, 92 consecutive patients who underwent MIDP at NHO Kyushu Medical Center from July 2016 to August 2023 were enrolled in this retrospective study. In all patients, a reinforced black cartridge triple-row stapler (Covidien Japan, Tokyo, Japan) was used during MIDP. The primary endpoint was the incidence of clinically relevant POPF. The risk factors for POPF were evaluated using multivariate analysis. RESULTS: Among the 92 patients, 74 underwent laparoscopic distal pancreatectomy and 18 underwent robot-assisted distal pancreatectomy. Clinically relevant POPF occurred in seven (7.6%) of 92 patients. The rate of severe complications (Clavien-Dindo grade ≥III) was 10.8%, and the mortality rate was 0%. The median postoperative hospital stay was 14 days. Multivariate logistic regression analysis showed that the independent risk factor for clinically relevant POPF after MIDP with a reinforced stapler was a body mass index of ≥22.6 kg/m2 (p=0.050, odds ratio=7.60). CONCLUSION: This study confirmed the safety and efficacy of reinforced staplers for preventing POPF after MIDP. A high body mass index was the only risk factor for clinically relevant POPF after MIDP with a reinforced stapler.

Laparoscopic Total Pancreatectomy After Laparoscopic Whipple.

BACKGROUND: The incidence of a second de novo pancreatic ductal adenocarcinoma (PDAC) among patients with prior cancer has been reported to be 6%.1,2 however, as survival increases through improvements in systemic therapy, this incidence of a de novo PDAC after prior PDAC may become more prevalent.3-8 In this context, a structured and stepwise approach to a total pancreatectomy for a second de novo PDAC after a prior PDAC treated with a pancreaticoduodenectomy is detailed. PATIENTS: We present two similar cases. The first patient was a 71-year-old female with de novo body PDAC, and the second was a 50-year-old female with de novo tail PDAC. To rule out recurrence, immunohistochemical staining as well as the review of biopsies by two experienced pathologists were employed. Both patients had undergone a laparoscopic pancreatoduodenectomy for PDAC 4 and 3 years prior. Each patient received four cycles of neoadjuvant chemotherapy and underwent a safe laparoscopic total pancreatectomy. TECHNIQUE: Prior to surgery, three-dimensional anatomic and port site modeling is performed to optimize the understanding of the spatial relationship between the tumor, blood vessels, and adjacent organs involved. The port site modeling (including pneumoperitoneum simulation) focuses on the optimal port set-up for dissecting the biliopancreatic limb off the portal vein. Following complete mobilization of the biliopancreatic limb, the biliopancreatic limb is staple-divided between the hepatico- and pancreaticojejunostomy. Great care must be taken to avoid accidental staple injury to the hepatic artery or celiac trunk. The remainder of the dissection is akin to a standard distal pancreaticosplenectomy. CONCLUSION: Virtual pancreatectomy modeling facilitates an optimal set-up for the critical step of this case, i.e. dissection of the pancreaticojejunostomy off the portal vein. Early division of the biliopancreatic limb between hepatico- and pancreatojejunostomy is crucial to facilitating the remainder of the dissection. Laparoscopic total pancreatectomy for a de novo PDAC after laparoscopic pancreaticoduodenectomy may become more common as survival of patients with prior PDAC improves over time.

The utility of axial imaging among selected patients in the early postoperative period after pancreatectomy.

BACKGROUND: Postoperative computed tomography imaging has been shown to play an important role in avoiding failure-to-rescue. We sought to examine the impact of the timing of such imaging studies on outcomes after pancreatectomy. METHODS: Patients who underwent pancreatic resection at our institution from 2017 to 2022 were reviewed retrospectively to identify those undergoing computed tomography for any indication before discharge. Patients were subdivided by the postoperative day that the first computed tomography scan was obtained: immediate (postoperative day <3), early (postoperative day 3-7), and delayed (postoperative day >7). RESULTS: Of 370 patients, 110 (30%) had a computed tomography during the initial surgical stay. The 3 timing groups were similar in age, comorbidities, pathology, operative time, and number of scans. When comparing the early with the delayed group, we found that antibiotic usage, percutaneous drainage, and overall invasive interventions during surgical stay were all similar. However, those patients who were scanned in the early period had significantly shorter length of stay (17.05 vs 22.82, P = .0008) and fewer composite days hospitalized (20.1 vs 24.9, P = .01) relative to the delayed group. Importantly, early computed tomography imaging was found to be the only independent predictor of a postoperative length of stay ≤15 days on multivariate analysis. Surgical stay mortality rates were significantly lower in the early compared with delayed group (0% vs 11%, P = .02). A change in treatment was observed in 59% after computed tomography, with 15% undergoing invasive interventions, 27% treated medically, and 16% with expectant management. CONCLUSION: In our cohort, patients imaged early after pancreatectomy experienced shorter hospital stays and lower inpatient mortality relative to those scanned after the first postoperative week.

Early mobilization after pancreatic surgery: A randomized controlled trial.

BACKGROUND: Pancreatic surgery has long been burdened with high postoperative morbidity. Early mobilization has been advocated to prevent complications and improve functional capacity. However, there is a lack of high-quality evidence supporting how to implement early mobilization and its independent impact on postoperative outcomes. The aim of this study was to investigate the effectiveness of implementing early mobilization in reducing postoperative complications and enhancing recovery in patients undergoing pancreatic surgery. METHODS: We conducted a single-blind, randomized trial in patients who underwent pancreatic surgery in a tertiary hospital in China. Eligible participants were randomly assigned to either the control group or the intervention group. Patients in the control group received usual care, whereas those in the intervention group received the early enforced mobilization protocol. The protocol consisted of 2 key components: professional assistance with the first ambulation on postoperative day 1 and family-involved supervision to achieve daily walking goals. The primary outcome was postoperative complications within 30 days, measured by the Comprehensive Complication Index. Secondary outcomes were postoperative mobilization, time to recovery of gastrointestinal function, postoperative pulmonary complications, pancreatic surgery-specific complications, patient-reported outcome measures, and 30-day readmission and mortality. RESULTS: A total of 135 patients were enrolled: 67 in the intervention group and 68 in the control group. The median Comprehensive Complication Index was not statistically significant between groups (mean difference -1.7; 95% confidence interval -8.7 to 0). Patients in the intervention group had earlier first ambulation postoperatively, walked greater distances on postoperative days 1-7, and had earlier time to first defecation. Trends for improvement in patient-reported outcomes showed that scores of Quality of Recovery 15 at postoperative day 3, physical function of Quality of Life Questionnaire C30 at postoperative day 7, and global quality of life at postoperative day 30 were significantly greater in the intervention group. There was no between-group difference in other domains of the Quality of Life Questionnaire C30 or other secondary outcome measures. CONCLUSION: Early enforced mobilization intervention did not reduce postoperative complications of patients undergoing pancreatic surgery, but it can enhance postoperative mobilization and improve the recovery of gastrointestinal function and patient-perceived quality of recovery.

Prognostic Factors for Early Recurrence After Resection of Pancreatic Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: More than half of pancreatic ductal adenocarcinomas (PDACs) recur within 12 months after curative-intent resection. This systematic review and meta-analysis was conducted to identify all reported prognostic factors for early recurrence in resected PDACs. METHODS: After a systematic literature search, a meta-analysis was conducted using a random effects model. Separate analyses were performed for adjusted vs unadjusted effect estimates as well as reported odds ratios (ORs) and hazard ratios (HRs). Risk of bias was assessed using the Quality in Prognostic Studies tool, and evidence was rated according to Grading of Recommendations Assessment, Development and Evaluation recommendations. RESULTS: After 2903 abstracts were screened, 65 studies were included. Of these, 28 studies (43.1%) defined early recurrence as evidence of recurrence within 6 months, whereas 34 (52.3%) defined it as evidence of recurrence within 12 months after surgery. Other definitions were uncommon. Analysis of unadjusted ORs and HRs revealed 41 and 5 prognostic factors for early recurrence within 6 months, respectively. When exclusively considering adjusted data, we identified 25 and 10 prognostic factors based on OR and HR, respectively. Using a 12-month definition, we identified 38 (OR) and 15 (HR) prognostic factors from unadjusted data and 38 (OR) and 30 (HR) prognostic factors from adjusted data, respectively. On the basis of frequency counts of adjusted data, preoperative carbohydrate antigen 19-9, N status, nondelivery of adjuvant therapy, grading, and tumor size based on imaging were identified as key prognostic factors for early recurrence. CONCLUSIONS: Reported prognostic factors of early recurrence vary considerably. Identified key prognostic factors could aid in the development of a risk stratification framework for early recurrence. However, prospective validation is necessary.

Recurrent disease detection after resection of pancreatic ductal adenocarcinoma using a recurrence-focused surveillance strategy (RADAR-PANC): protocol of an international randomized controlled trial according to the Trials within Cohorts design.

BACKGROUND: Disease recurrence remains one of the biggest concerns in patients after resection of pancreatic ductal adenocarcinoma (PDAC). Despite (neo)adjuvant systemic therapy, most patients experience local and/or distant PDAC recurrence within 2 years. High-level evidence regarding the benefits of recurrence-focused surveillance after PDAC resection is missing, and the impact of early detection and treatment of recurrence on survival and quality of life is unknown. In most European countries, recurrence-focused follow-up after surgery for PDAC is currently lacking. Consequently, guidelines regarding postoperative surveillance are based on expert opinion and other low-level evidence. The recent emergence of more potent local and systemic treatment options for PDAC recurrence has increased interest in early diagnosis. To determine whether early detection and treatment of recurrence can lead to improved survival and quality of life, we designed an international randomized trial. METHODS: This randomized controlled trial is nested within an existing prospective cohort in pancreatic cancer centers in the Netherlands (Dutch Pancreatic Cancer Project; PACAP) and the United Kingdom (UK) (Pancreas Cancer: Observations of Practice and survival; PACOPS) according to the "Trials within Cohorts" (TwiCs) design. All PACAP/PACOPS participants with a macroscopically radical resection (R0-R1) of histologically confirmed PDAC, who provided informed consent for TwiCs and participation in quality of life questionnaires, are included. Participants randomized to the intervention arm are offered recurrence-focused surveillance, existing of clinical evaluation, serum cancer antigen (CA) 19-9 testing, and contrast-enhanced computed tomography (CT) of chest and abdomen every three months during the first 2 years after surgery. Participants in the control arm of the study will undergo non-standardized clinical follow-up, generally consisting of clinical follow-up with imaging and serum tumor marker testing only in case of onset of symptoms, according to local practice in the participating hospital. The primary endpoint is overall survival. Secondary endpoints include quality of life, patterns of recurrence, compliance to and costs of recurrence-focused follow-up, and the impact on recurrence-focused treatment. DISCUSSION: The RADAR-PANC trial will be the first randomized controlled trial to generate high level evidence for the current clinical equipoise regarding the value of recurrence-focused postoperative surveillance with serial tumor marker testing and routine imaging in patients after PDAC resection. The Trials within Cohort design allows us to study the acceptability of recurrence-focused surveillance among cohort participants and increases the generalizability of findings to the general population. While it is strongly encouraged to offer all trial participants treatment at time of recurrence diagnosis, type and timing of treatment will be determined through shared decision-making. This might reduce the potential survival benefits of recurrence-focused surveillance, although insights into the impact on patients' quality of life will be obtained. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04875325 . Registered on May 6, 2021.

Impact of pancreas transection site on incidence of pancreatic fistula after distal pancreatectomy: a propensity score matched study.

BACKGROUND: Distal pancreatectomy (DP) is performed for lesions in the body and tail of the pancreas. The morbidity profile is considerable, mainly due to clinically relevant postoperative pancreatic fistula (CR-POPF). This study aims to investigate potential differences in CR-POPF related to transection site. METHODS: An observational cohort study from a prospectively maintained database was performed. Subtotal distal pancreatectomy (SDP) was defined as transection over the superior mesenteric vein, and DP was defined as transection lateral to this point. Propensity score matching (PSM) in 1:1 fashion was applied based on demographical and perioperative variables. RESULTS: Six hundred and six patients were included in the analysis (1997-2020). Four hundred twenty (69.3%) underwent DP, while 186 (30.7%) underwent SDP. The rate of CR-POPF was 19.3% after DP and 20.4% after SDP (p = 0.74). SDP was associated with older age (63.1 vs 60.1 years, p = 0.016), higher occurrence of ductal adenocarcinoma (37.1 vs 17.6%, p = 0.001) and more frequent use of neoadjuvant chemotherapy (3.8 vs 0.7%, p = 0.012). After PSM, 155 patients were left in each group. The difference in CR-POPF between DP and SDP remained statistically non-significant (20.6 vs 18.7%, p = 0.67). CONCLUSION: This study found no difference in CR-POPF related to transection site during distal pancreatectomy.