Interaction analysis of subgroup effects in randomized trials: the essential methodological points.

Subgroup analysis aims to identify subgroups (usually defined by baseline/demographic characteristics), who would (or not) benefit from an intervention under specific conditions. Often performed post hoc (not pre-specified in the protocol), subgroup analyses are prone to elevated type I error due to multiple testing, inadequate power, and inappropriate statistical interpretation. Aside from the well-known Bonferroni correction, subgroup treatment interaction tests can provide useful information to support the hypothesis. Using data from a previously published randomized trial where a p value of 0.015 was found for the comparison between standard and Hemopatch® groups in (the subgroup of) 135 patients who had hand-sewn pancreatic stump closure we first sought to determine whether there was interaction between the number and proportion of the dependent event of interest (POPF) among the subgroup population (patients with hand-sewn stump closure and use of Hemopatch®), Next, we calculated the relative excess risk due to interaction (RERI) and the "attributable proportion" (AP). The p value of the interaction was p = 0.034, the RERI was - 0.77 (p = 0.0204) (the probability of POPF was 0.77 because of the interaction), the RERI was 13% (patients are 13% less likely to sustain POPF because of the interaction), and the AP was - 0.616 (61.6% of patients who did not develop POPF did so because of the interaction). Although no causality can be implied, Hemopatch® may potentially decrease the POPF after distal pancreatectomy when the stump is closed hand-sewn. The hypothesis generated by our subgroup analysis requires confirmation by a specific, randomized trial, including only patients undergoing hand-sewn closure of the pancreatic stump after distal pancreatectomy.Trial registration: INS-621000-0760.

Associations of body composition parameters with postoperative outcome and perineural tumour invasion after oncological pancreatic resection.

BACKGROUND: Pancreatic cancer is often accompanied by wasting conditions. While surgery is the primary curative approach, it poses a substantial risk of postoperative complications, hindering subsequent treatments. Therefore, identifying patients at high risk for complications and optimizing their perioperative general condition is crucial. Sarcopenia and other body composition abnormalities have shown to adversely affect surgical and oncological outcomes in various cancer patients. As most pancreatic tumours are located close to the neuronal control centre for the digestive tract, it is possible that neural infiltration in this area deranges bowel functions and contributes to malabsorption and malnutrition and ultimately worsen sarcopenia and weight loss. METHODS: A retrospective analysis of CT scans was performed for pancreatic cancer patients who underwent surgical tumour resection at a single high-volume centre from 2007 to 2023. Sarcopenia prevalence was assessed by skeletal muscle index (SMI), and visceral obesity was determined by the visceral adipose tissue area (VAT). Obesity and malnutrition were determined by the GLIM criteria. Sarcopenic obesity was defined as simultaneous sarcopenia and obesity. Postoperative complications, mortality and perineural tumour invasion, were compared among patients with body composition abnormalities. RESULTS: Of 437 patients studied, 46% were female, the median age was 69 (61;74) years. CT analysis revealed 54.9% of patients with sarcopenia, 23.7% with sarcopenic obesity and 45.9% with visceral obesity. Sarcopenia and sarcopenic obesity were more prevalent in elderly and male patients. Postoperative surgical complications occurred in 67.7% of patients, most of which were mild (41.6%). Severe complications occurred in 22.7% of cases and the mortality rate was 3.4%. Severe postoperative complications were significantly more common in patients with sarcopenia or sarcopenic obesity. Visceral obesity or malnutrition based on BMI alone, did not significantly impact complications. Perineural invasion was found in 80.1% of patients and was unrelated to malnutrition or body composition parameters. CONCLUSIONS: This is the first and largest study evaluating the associations of CT-based body mass analysis with surgical outcome and histopathological perineural tumour invasion in pancreatic cancer patients. The results suggest that elderly and male patients are at high risk for sarcopenia and should be routinely evaluated by CT before undergoing pancreatic surgery, irrespective of their BMI. Confirmation of the results in prospective studies is needed to assess if pancreatic cancer patients with radiographic sarcopenia benefit from preoperative amelioration of muscle mass and function by exercise and nutritional interventions.

Clinical significance of postoperative complications after pancreatic surgery in time-to-complication and length of postoperative hospital stay: a retrospective study.

PURPOSE: We retrospectively analyzed pancreatectomy patients and examined the occurrence rate and timing of postoperative complications (time-to-complication; TTC) and their impact on the length of postoperative hospital stay (POHS) to clarify their characteristics, provide appropriate postoperative management, and improve short-term outcomes in the future. METHODS: A total of 227 patients, composed of 118 pancreaticoduodenectomy (PD) and 109 distal pancreatectomy (DP) cases, were analyzed. We examined the frequency of occurrence, TTC, and POHS of each type of postoperative complication, and these were analyzed for each surgical procedure. Complications of the Clavien-Dindo (CD) classification Grade II or higher were considered clinically significant. RESULTS: Clinically significant complications were observed in 70.3% and 36.7% of the patients with PD and DP, respectively. Complications occurred at a median of 10 days in patients with PD and 6 days in patients with DP. Postoperative pancreatic fistula (POPF) occurred approximately 7 days postoperatively in both groups. For the POHS, in cases without significant postoperative complications (CD ≤ I), it was approximately 22 days for PD and 11 days for DP. In contrast, when any complications occurred, POHS increased to 30 days for PD and 19 days for DP (each with additional 8 days), respectively. In particular, POPF prolonged the hospital stay by approximately 11 days for both procedures. CONCLUSION: Each postoperative complication after pancreatectomy has its own characteristics in terms of the frequency of occurrence, TTC, and impact on POHS. A correct understanding of these factors will enable timely therapeutic intervention and improve short-term outcomes after pancreatectomy.

Association between chronic pancreatitis and pancreatic cancer at a central hospital in KwaZulu-Natal, South Africa.

BACKGROUND: The frequency of histological chronic pancreatitis (CP) evidence in the resident pancreas of resected periampullary cancers (PACs) has never been studied in Africa. This study aims to describe the spectrum of pathology and outcomes of pancreatic surgeries and address this deficit from a South African central hospital cohort. METHODS: A retrospective audit of patients undergoing pancreatic surgery at Inkosi Albert Luthuli Central Hospital (IALCH) between 2003 and 2023 was conducted. The patient demographics, human immunodeficiency virus (HIV) status, histological subtypes, type and extent of surgery, and 30-day and overall mortality were captured from medical records. The presence of CP in the resident pancreas of patients resected for pancreatic and PAC was obtained from the pathology reports. RESULTS: Of the cohort, 72% were Africans, presenting at an earlier average age than other races. Surgery was performed on 126 (107 for cancer, 19 for CP) patients. Of these, 77 were pancreaticoduodenectomy (PD), of which 34 were for pancreatic ductal adenocarcinoma (PDAC). The prevalence of CP in the resident pancreas was 29.9%, and 55.9% in PDAC. Age was the only factor significantly associated with 30-day mortality, as well as long-term survival amongst patients with pancreatic and PAC. The overall median survival for patients with PAC was seven months; 11 patients are alive. CONCLUSION: In a predominantly African cohort undergoing pancreatic surgery, PDAC presents at a younger age. The high perioperative mortality and low overall survival (OS) in the setting of high CP prevalence in the resident pancreas requires further investigation of its role in the aetiopathogenesis and prognosis in PDAC.

Effect of preoperative biliary drainage on intraoperative biliary cultures and surgical outcomes after pancreatic resection.

BACKGROUND: Prolonged obstructive jaundice (OJ), associated with resectable pancreatic pathology, has many deleterious effects that are potentially rectifiable by preoperative biliary drainage (POBD) at the cost of increased postoperative infective complications. The aim of this study is to assess the impact of POBD on intraoperative biliary cultures (IBCs) and surgical outcomes in patients undergoing pancreatic resection. METHODS: Data from patients at Groote Schuur Hospital, Cape Town, between October 2008 and May 2019 were analysed. Demographic, clinical, and outcome variables were evaluated, including perioperative morbidity, mortality, and 5-year survival. RESULTS: Among 128 patients, 69.5% underwent POBD. The overall perioperative mortality in this study was 8.8%. The POBD group had a significantly lower perioperative mortality rate compared to the non-drainage group (5.6% vs. 25.6%). POBD patients had a higher incidence of surgical site infections (55.1% vs. 23.1%), polymicrobial growth from IBCs and were more likely to culture resistant organisms. Five-year survival was similar in the two groups. CONCLUSION: POBD was associated with a high incidence of resistant organisms on the IBCs, a high incidence of surgical site infections and a high correlation between cultures from the surgical site infection and the IBCs.

One hundred consecutive pancreatic resections using a novel pancreatico-jejunostomy technique.

BACKGROUND: No single technique of remnant pancreas reconstruction after pancreaticoduodenectomy (PD) has been demonstrated to be superior to the others in the prevention of post-operative pancreatic fistula (POPF), and the accumulation of surgical experience is closely related to the quality of this anastomosis. The aim of the current study was to evaluate the feasibility and patient outcomes of a simplified technique involving a single-layer continuous pancreaticojejunostomy (PJA) with Falciform ligament reinforcement that can be used with all types of pancreases. METHODS: A single-centre and single-surgeon study was performed. One hundred consecutive patients undergoing pancreatic resection with subsequent PJA using a novel technique performed by a single surgeon were included in the study. Patient demographics, pre-operative treatments, risk factors for POPF, and post-operative morbidity and mortality and long-term patient outcome were prospectively recorded and reported. RESULTS: From March 2018 to March 2022, 59 male and 41 female patients were included. 91 patients underwent PD for malignancy with 32 receiving neoadjuvant treatment. 59 patients were classified as intermediate/high risk for POPF according to validated fistula prediction models. There were 12 POPF Type B and 2 POPF Type C. The overall morbidity rate was 16% with no 90-day mortality. 3 patients underwent reoperation. The median length of hospitalisation was 12.6 days and 82% of eligible patients commenced and completed adjuvant chemotherapy. CONCLUSION: Single-layer continuous dunking PJA with Falciform ligament reinforcement is a simplified and feasible method for PJA with a low associated complication rate.

Scope transition and early arterial inflow control provide safe and comfortable dissection in robotic distal pancreatectomy.

PURPOSE: We describe details and outcomes of a novel technique for optimizing the surgical field during robotic distal pancreatectomy (RDP) for distal pancreatic lesions, which has become common with potential advantages over laparoscopic surgery. METHODS: For suprapancreatic lymph node dissection and splenic artery ligation, we used the basic center position with a scope through the midline port. During manipulation of the perisplenic area, the left position was used by moving the scope to the left medial side. The left lateral position is optionally used by moving the scope to the left lateral port when scope access to the perisplenic area is difficult. In addition, early splenic artery clipping and short gastric artery dissection for inflow block were performed to minimize bleeding around the spleen. We evaluated retrospectively the surgical outcomes of our method using a scoring system that allocated one point for blood inflow control and one point for optimizing the surgical view in the left position. RESULTS: We analyzed 34 patients who underwent RDP or R-radical antegrade modular pancreatosplenectomy (RAMPS). The left position was applied in 14 patients, and the left lateral position was applied in 6. Based on the scoring system, only the 0-point group (n = 8) had four bleeding cases (50%) with splenic injury or blood pooling; the other 1-point or 2-point groups (n = 13, respectively) had no bleeding cases (p = 0.0046). CONCLUSION: Optimization of the surgical field using scope transition and inflow control ensured safe dissection during RDP.

Multivisceral Oncological Resections Involving the Pancreas: Protocol for a Systematic Review and Meta-Analysis.

BACKGROUND: With the continuous advancement of cancer treatments, a comprehensive analysis of the impact of multivisceral oncological pancreatic resections on morbidity, mortality, and long-term survival is currently lacking. OBJECTIVE: This manuscript presents the protocol for a systematic review and meta-analysis designed to summarize the existing evidence concerning the outcomes of multivisceral oncological pancreatic resections across diverse tumor entities. METHODS: We will conduct a systematic search of the PubMed or MEDLINE, Embase, Cochrane Library, CINAHL, and ClinicalTrials.gov databases in strict accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The predefined outcomes encompass postoperative mortality, postoperative morbidity, overall and disease-free survival (1- to 5-year survival rates), the proportion of macroscopically complete (R0) resections (according to the Royal College of Pathologists definition), duration of hospital stay (in days), reoperation rate (%), postoperative complications (covering all complications according to the Clavien-Dindo classification), as well as pancreatic fistula, postpancreatectomy hemorrhage, and delayed gastric emptying (all according to the definitions of the International Study Group of Pancreas Surgery). RESULTS: Systematic database searches will begin in July 2024. The completion of the meta-analysis is anticipated by December 2024. Before completion, the literature search will be checked for new publications that must be considered in the context of the work. CONCLUSIONS: The forthcoming findings will provide an up-to-date overview of the feasibility, safety, and oncological efficacy of multivisceral pancreatic resections across diverse tumor entities. This data will serve as a valuable resource for health care professionals and patients to make well-informed clinical decisions. TRIAL REGISTRATION: PROSPERO CRD42023437858; https://tinyurl.com/bde5xmfw. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/54089.

Safety and feasibility of minimally invasive distal pancreatectomy for pancreatic cancer in elderly patients: A retrospective study.

INTRODUCTION: Previous studies have not evaluated the surgical difficulty of minimally invasive distal pancreatectomy for pancreatic cancer in elderly patients. Therefore, we aimed to investigate the effect of elderly age on the perioperative outcomes of minimally invasive distal pancreatectomy, focusing on surgical difficulty. METHODS: This single-center retrospective study included patients who underwent minimally invasive distal pancreatectomy for pancreatic cancer at Kansai Rosai Hospital between September 2012 and December 2023. Perioperative outcomes were investigated between the elderly (>75 years) and non-elderly (≤75 years) groups. RESULTS: Fifty-six patients were included: 26 and 30 in the elderly and non-elderly groups, respectively. The median operative time was significantly shorter in the elderly group than in the non-elderly group (324 vs. 414 min, p = .022), but other surgical outcomes were not significantly different including oncological factors. The median difficulty score was similar between the elderly and non-elderly groups (6 vs. 7, respectively; p = .699). The incidences of postoperative complications and pancreatic fistulas were not significantly different in the elderly and non-elderly groups (23% vs. 43%, p = .159, and 19% vs. 36%, p = .236, respectively), even though analyzed in subgroups with low-to-intermediate or high difficulty score. CONCLUSIONS: The safety and feasibility of minimally invasive distal pancreatectomy for pancreatic cancer were not significantly different between elderly and non-elderly patients, even when surgical difficulty was considered. This surgical procedure can be safe and feasible for elderly patients.

Middle-segment preserving pancreatectomy: a literature review and case report.

PURPOSE: Middle segment-preserving pancreatectomy (MSPP) is a relatively new parenchymal-sparing surgery that has been introduced as an alternative to total pancreatectomy (TP) for multicentric benign and borderline pancreatic diseases. To date, only 36 cases have been reported in English. METHODS: We reviewed 22 published articles on MSPP and reported an additional case. RESULTS: Our patient was a 49-year-old Japanese man diagnosed with Zollinger-Elison syndrome (ZES) caused by duodenal and pancreatic gastrinoma associated with multiple endocrine neoplasia syndrome type 1. We avoided TP and chose MSPP as the operative technique due to his relatively young age. The patient developed a grade B postoperative pancreatic fistula (POPF), which improved with conservative treatment. He was discharged without further treatment. To date, no tumor has recurred, and pancreatic function seems to be maintained. According to a literature review, the morbidity rate of MSPP is as high as 54%, mainly due to the high incidence of POPF (32%). In contrast, there was no perioperative mortality, and postoperative pancreatic function was comparable to that after conventional pancreatectomy. CONCLUSIONS: Despite the high incidence of POPF, MSPP appears to be safe, with low perioperative mortality and good postoperative pancreatic sufficiency.

Hemorrhagic Cysts in the Pancreas: Risk Factors, Treatment, and Outcomes - Insights from a Single-Center Study.

BACKGROUND Hemorrhagic cysts are rarely discussed subtypes of pancreatic pseudocysts that occur in about 10% of these cases. They are caused by erosion of the walls of neighboring vessels by extravasated proteolytic pancreatic enzymes. A retrospective analysis was performed to clinically characterize risk factors, treatment, and outcome in patients with hemorrhagic cysts of the pancreas. MATERIAL AND METHODS The retrospective study included patients from the Department of Digestive Tract Surgery in Katowice, Poland, who were treated surgically for a pancreatic hemorrhagic cyst from January 2016 to November 2022. We gathered and assessed data on cyst etiology, symptoms, imaging examinations, risk factors, time, type, and complications of surgery. RESULTS The main symptom was abdominal pain, noted in 5 (62.5%) patients. The most common etiology of cyst was acute pancreatitis, which occurred in 5 patients (62.5%). The most common localization was the tail of pancreas, found in 3 patients (36.5%). The largest dimension of the cyst was 98±68 (30-200) mm. Every patient needed surgical intervention. Patients underwent distal pancreatectomy (n=3) or marsupialization (n=5). One (12.5%) postoperative complication was observed, while mortality was 0%. CONCLUSIONS Hemorrhagic cyst is a life-threatening complication of pancreatitis requiring immediate treatment. In most cases, open surgery is the treatment of choice. Despite the continuous development of minimally invasive techniques, surgical treatment remains the only effective treatment method. Depending on the cyst localization and technical possibilities, pancreatectomy or marsupialization can be applied, and both of them have low complication and mortality rates.

Prolonged pre-firing pancreatic compression with linear staplers in distal pancreatectomy: a valuable technique for post-operative pancreatic fistula prevention.

PURPOSE: Post-operative pancreatic fistula (POPF) remains the main complication after distal pancreatectomy (DP). The aim of this study is to evaluate the potential benefit of different durations of progressive stapler closure on POPF rate and severity after DP. METHODS: Patients who underwent DP between 2016 and 2023 were retrospectively enrolled and divided into two groups according to the duration of the stapler closure: those who underwent a progressive compression for < 10 min and those for ≥ 10 min. RESULTS: Among 155 DPs, 83 (53.5%) patients underwent pre-firing compression for < 10 min and 72 (46.5%) for ≥ 10 min. As a whole, 101 (65.1%) developed POPF. A lower incidence rate was found in case of ≥ 10 min compression (34-47.2%) compared to < 10 min compression (67- 80.7%) (p = 0.001). When only clinically relevant (CR) POPFs were considered, a prolonged pre-firing compression led to a lower rate (15-20.8%) than the < 10 min cohort (32-38.6%; p = 0.02). At the multivariate analysis, a compression time of at least 10 min was confirmed as a protective factor for both POPF (OR: 5.47, 95% CI: 2.16-13.87; p = 0.04) and CR-POPF (OR: 2.5, 95% CI: 1.19-5.45; p = 0.04) development. In case of a thick pancreatic gland, a prolonged pancreatic compression for at least 10 min was significantly associated to a lower rate of CR-POPF compared to < 10 min (p = 0.04). CONCLUSION: A prolonged pre-firing pancreatic compression for at least 10 min seems to significantly reduce the risk of CR-POPF development. Moreover, significant advantages are documented in case of a thick pancreatic gland.

Assessing quality of hepato-pancreato-biliary surgery: nationwide benchmarking.

BACKGROUND: Clinical auditing is a powerful tool to evaluate and improve healthcare. Deviations from the expected quality of care are identified by benchmarking the results of individual hospitals using national averages. This study aimed to evaluate the use of quality indicators for benchmarking hepato-pancreato-biliary (HPB) surgery and when outlier hospitals could be identified. METHODS: A population-based study used data from two nationwide Dutch HPB audits (DHBA and DPCA) from 2014 to 2021. Sample size calculations determined the threshold (in percentage points) to identify centres as statistical outliers, based on current volume requirements (annual minimum of 20 resections) on a two-year period (2020-2021), covering mortality rate, failure to rescue (FTR), major morbidity rate and textbook/ideal outcome (TO) for minor liver resection (LR), major LR, pancreaticoduodenectomy (PD) and distal pancreatectomy (DP). RESULTS: In total, 10 963 and 7365 patients who underwent liver and pancreatic resection respectively were included. Benchmark and corresponding range of mortality rates were 0.6% (0 -3.2%) and 3.3% (0-16.7%) for minor and major LR, and 2.7% (0-7.0%) and 0.6% (0-4.2%) for PD and DP respectively. FTR rates were 5.4% (0-33.3%), 14.2% (0-100%), 7.5% (1.6%-28.5%) and 3.1% (0-14.9%). For major morbidity rate, corresponding rates were 9.8% (0-20.5%), 28.1% (0-47.1%), 36% (15.8%-58.3%) and 22.3% (5.2%-46.1%). For TO, corresponding rates were 73.6% (61.3%-94.4%), 54.1% (35.3-100), 46.8% (25.3%-59.4%) and 63.3% (30.7%-84.6%). Mortality rate thresholds indicating a significant outlier were 8.6% and 15.4% for minor and major LR and 14.2% and 8.6% for PD and DP. For FTR, these thresholds were 17.9%, 31.6%, 22.9% and 15.0%. For major morbidity rate, these thresholds were 26.1%, 49.7%, 57.9% and 52.9% respectively. For TO, lower thresholds were 52.5%, 32.5%, 25.8% and 41.4% respectively. Higher hospital volumes decrease thresholds to detect outliers. CONCLUSION: Current event rates and minimum volume requirements per hospital are too low to detect any meaningful between hospital differences in mortality rate and FTR. Major morbidity rate and TO are better candidates to use for benchmarking.

Thirty-day prevalence and clinical impact of fluid collections at the resection margin after distal pancreatectomy: Follow-up of a multicentric randomized controlled trial.

BACKGROUND: Postoperative fluid collections at the resection margin of the pancreatic stump are frequent after distal pancreatectomy, yet their clinical impact is unclear. The aim of this study was to assess the 30-day prevalence of postoperative fluid collections after distal pancreatectomy and the factors associated with a clinically relevant condition. METHODS: Patients enrolled in a randomized controlled trial of parenchymal transection with either reinforced, triple-row staple, or ultrasonic dissector underwent routine magnetic resonance 30 days postoperatively. Postoperative fluid collection was defined as a cyst-like lesion of at least 1 cm at the pancreatic resection margin. Postoperative fluid collections requiring any therapy were defined as clinically relevant. RESULTS: A total of 133 patients were analyzed; 69 were in the triple-row staple transection arm, and 64 were in the ultrasonic dissector transection arm. The overall 30-day prevalence of postoperative fluid collections was 68% (n = 90), without any significant difference between the two trial arms. Postoperative serum hyperamylasemia was more frequent in patients with postoperative fluid collections than those without (31% vs 7%, P = .001). Among the postoperative fluid collection population, an early postoperative pancreatic fistula (odds ratio 14.9, P = .002), post pancreatectomy acute pancreatitis (odds ratio 12.7, P = .036), and postoperative fluid collection size larger than 50 mm (odds ratio 6.6, P = .046) were independently associated with a clinically relevant postoperative fluid collection. CONCLUSION: Postoperative fluid collections at the resection margin are common after distal pancreatectomy and can be predicted by early assessment of postoperative serum hyperamylasemia. A preceding pancreatectomy acute pancreatitis and/or postoperative pancreatic fistula and large collections (>50 mm) were associated with a clinically relevant postoperative fluid collection, representing targets for closer follow-up or earlier therapeutic interventions.

Continuous drain irrigation as a risk mitigation strategy for postoperative pancreatic fistula: a meta-analysis.

BACKGROUND: Postoperative pancreatic fistula serves as the principle cause for the morbidity and mortality observed after pancreatectomy. Continuous drain irrigation as a treatment strategy for infected pancreatic necrosis has previously been described; however, its role adter pancreatectomy has yet to be determined. The aim of this study was to determine whether continuous drain irrigation reduces postoperative pancreatic fistula. METHODS: A meta-analysis of the pre-existing literature was performed. The primary end point was whether continuous drain irrigation reduced postoperative pancreatic fistula after pancreatectomy. The secondary end point evaluated its impact on postoperative morbidity, mortality, and length of stay. RESULTS: Nine articles involving 782 patients were included. Continuous drain irrigation use was associated with a statistically significant reduction in postoperative pancreatic fistula rates (odds ratio [95% confidence interval] 0.40 [0.19-0.82], P = .01). Upon subgroup analysis, a significant reduction in clinically relevant postoperative pancreatic fistula was also noted (odds ratio 0.37 [0.20-0.66], P = .0008). A reduction in postoperative complications was also observed-delayed gastric emptying (0.45 [0.24-0.84], P = .01) and the need for re-operation (0.33 [0.11-0.96], P = .04). This reduction in postoperative complications translated into a reduced length of stay (mean difference -2.62 [-4.97 to -0.26], P = .03). CONCLUSION: Continuous drain irrigation after pancreatectomy is a novel treatment strategy with a limited body of published evidence. After acknowledging the limitations of the data, initial analysis would suggest that it may serve as an effective risk mitigation strategy against postoperative pancreatic fistula. Further research in a prospective context utilizing patient risk stratification for fistula development is, however, required to define its role within clinical practice.

Correlation between relative dose intensity of adjuvant S-1 chemotherapy and psoas muscle mass volume and survival after resection of pancreatic ductal adenocarcinoma: A retrospective study.

This study aimed to investigate the prognostic relationship between relative dose intensity (RDI) of adjuvant S-1 chemotherapy and psoas muscle mass volume (PMV) in patients with resected pancreatic ductal adenocarcinoma. We enrolled 105 patients with histologically confirmed pancreatic ductal adenocarcinoma who had undergone pancreatectomy. Adjuvant S-1 chemotherapy was administered to 72 (68.6%) of the 105 patients and not to the remaining 33 patients. Patients who received adjuvant S-1 chemotherapy were stratified into high- and low-RDI groups by the cutoff value for RDI. Five-year overall survival (OS) and relapse-free survival (RFS) rates were significantly higher in the high- than in the low-RDI group. Similarly, both the 5-year OS and RFS rates were significantly greater among patients in the high-PMV group than among patients in the low-PMV group. The RDI was an independent prognostic factor in our study patients. Furthermore, patients who received adjuvant S-1 chemotherapy were stratified into 3 groups: those with both high RDI and high-PMV, Group A; those with either high RDI or high PMV (but not both), Group B; and those with both low RDI and low-PMV, group C. There were statistically significant differences in 5-year OS and RFS between 3 patient groups (5-year overall survival: P = .023, 5-year relapse-free survival: P = .001). The area under the curve for the combination of RDI and PMV (0.674) was greater than that for RDI alone (0.645). A sufficient dosage of adjuvant S-1 chemotherapy is important in improving survival of patients with resected pancreatic ductal adenocarcinoma. A combination of RDI and PMV may predict the prognosis of patients with resected pancreatic ductal adenocarcinoma more effective than RDI alone.

Evaluating the economic efficiency of open, laparoscopic, and robotic distal pancreatectomy: an updated systematic review and network meta-analysis.

BACKGROUND: This study compared the cost-effectiveness of open (ODP), laparoscopic (LDP), and robotic (RDP) distal pancreatectomy (DP). METHODS: Studies reporting the costs of DP were included in a literature search until August 2023. Bayesian network meta-analysis was conducted, and surface under cumulative ranking area (SUCRA) values, mean difference (MD), odds ratio (OR), and 95% credible intervals (CrIs) were calculated for outcomes of interest. Cluster analysis was performed to examine the similarity and classification of DP approaches into homogeneous clusters. A decision model-based cost-utility analysis was conducted for the cost-effectiveness analysis of DP strategies. RESULTS: Twenty-six studies with 29,164 patients were included in the analysis. Among the three groups, LDP had the lowest overall costs, while ODP had the highest overall costs (LDP vs. ODP: MD - 3521.36, 95% CrI - 6172.91 to - 1228.59). RDP had the highest procedural costs (ODP vs. RDP: MD - 4311.15, 95% CrI - 6005.40 to - 2599.16; LDP vs. RDP: MD - 3772.25, 95% CrI - 4989.50 to - 2535.16), but incurred the lowest hospitalization costs. Both LDP (MD - 3663.82, 95% CrI - 6906.52 to - 747.69) and RDP (MD - 6678.42, 95% CrI - 11,434.30 to - 2972.89) had significantly reduced hospitalization costs compared to ODP. LDP and RDP demonstrated a superior profile regarding costs-morbidity, costs-mortality, costs-efficacy, and costs-utility compared to ODP. Compared to ODP, LDP and RDP cost $3110 and $817 less per patient, resulting in 0.03 and 0.05 additional quality-adjusted life years (QALYs), respectively, with positive incremental net monetary benefit (NMB). RDP costs $2293 more than LDP with a negative incremental NMB but generates 0.02 additional QALYs with improved postoperative morbidity and spleen preservation. Probabilistic sensitivity analysis suggests that LDP and RDP are more cost-effective options compared to ODP at various willingness-to-pay thresholds. CONCLUSION: LDP and RDP are more cost-effective than ODP, with LDP exhibiting better cost savings and RDP demonstrating superior surgical outcomes and improved QALYs.

The radiomorphological appearance of the invasive margin in pancreatic cancer is associated with tumor budding.

PURPOSE: Pancreatic cancer (PDAC) is characterized by infiltrative, spiculated tumor growth into the surrounding non-neoplastic tissue. Clinically, its diagnosis is often established by magnetic resonance imaging (MRI). At the invasive margin, tumor buds can be detected by histology, an established marker associated with poor prognosis in different types of tumors. METHODS: We analyzed PDAC by determining the degree of tumor spiculation on T2-weighted MRI using a 3-tier grading system. The grade of spiculation was correlated with the density of tumor buds quantified in histological sections of the respective surgical specimen according to the guidelines of the International Tumor Budding Consensus Conference (n = 28 patients). RESULTS: 64% of tumors revealed intermediate to high spiculation on MRI. In over 90% of cases, tumor buds were detected. We observed a significant positive rank correlation between the grade of radiological tumor spiculation and the histopathological number of tumor buds (rs = 0.745, p < 0.001). The number of tumor buds was not significantly associated with tumor stage, presence of lymph node metastases, or histopathological grading (p ≥ 0.352). CONCLUSION: Our study identifies a readily available radiological marker for non-invasive estimation of tumor budding, as a correlate for infiltrative tumor growth. This finding could help to identify PDAC patients who might benefit from more extensive peripancreatic soft tissue resection during surgery or stratify patients for personalized therapy concepts.

Effect of artificial or autologous coverage of the pancreatic remnant or anastomosis on postoperative pancreatic fistulas after partial pancreatectomy: meta-analysis of randomized clinical trials.

BACKGROUND: Postoperative pancreatic fistulas remain a driver of major complications after partial pancreatectomy. It is unclear whether coverage of the anastomosis or pancreatic remnant can reduce the incidence of postoperative pancreatic fistulas. The aim of this study was to evaluate the effect of autologous or artificial coverage of the pancreatic remnant or anastomosis on outcomes after partial pancreatectomy. METHODS: A systematic literature search was performed using MEDLINE and the Cochrane Central Register of Controlled Trials (CENTRAL) up to March 2024. All RCTs analysing a coverage method in patients undergoing partial pancreatoduodenectomy or distal pancreatectomy were included. The primary outcome was postoperative pancreatic fistula development. Subgroup analyses for pancreatoduodenectomy or distal pancreatectomy and artificial or autologous coverage were conducted. RESULTS: A total of 18 RCTs with 2326 patients were included. In the overall analysis, coverage decreased the incidence of postoperative pancreatic fistulas by 29% (OR 0.71, 95% c.i. 0.54 to 0.93, P < 0.01). This decrease was also seen in the 12 RCTs covering the remnant after distal pancreatectomy (OR 0.69, 95% c.i. 0.51 to 0.94, P < 0.02) and the 4 RCTs applying autologous coverage after pancreatoduodenectomy and distal pancreatectomy (OR 0.53, 95% c.i. 0.29 to 0.96, P < 0.04). Other subgroup analyses (artificial coverage or pancreatoduodenectomy) showed no statistically significant differences. The secondary endpoints of mortality, reoperations, and re-interventions were each affected positively by the use of coverage techniques. The certainty of evidence was very low to moderate. CONCLUSION: The implementation of coverage, whether artificial or autologous, is beneficial after partial pancreatectomy, especially in patients undergoing distal pancreatectomy with autologous coverage.

Efficacy of Pancreatic Dissection With a Triple-row Stapler in Laparoscopic Distal Pancreatectomy: A Retrospective Observational Study.

BACKGROUND: Postoperative pancreatic fistulas (POPFs) occur after 20% to 30% of laparoscopic distal pancreatectomies. This study aimed to evaluate the clinical efficacy of laparoscopic distal pancreatectomy using triple-row staplers in preventing POPFs. METHODS: Between April 2016 and May 2023, 59 patients underwent complete laparoscopic distal pancreatectomies. There were more females (n=34, 57.6%) than males (n=25, 42.4%). The median age of the patients was 68.9 years. The patients were divided into slow-compression (n=19) and no-compression (n=40) groups and examined for pancreatic leakage. Both groups were examined with respect to age, sex, body mass index (BMI), pancreatic thickness at the pancreatic dissection site, pancreatic texture, diagnosis, operative time, blood loss, presence of POPF, date of drain removal, and length of hospital stay. In addition, risk factors for POPF were examined in a multivariate analysis. RESULTS: Grade B POPFs were found in 9 patients (15.3%). Using univariate analysis, the operative time, blood loss, postoperative pancreatic fluid leakage, day of drain removal, and hospital stay were shorter in the no-compression group than in the slow-compression group. Using multivariate analysis, the absence of POPFs was significantly more frequent in the no-compression group (odds ratio, 5.69; 95% CI, 1.241-26.109; P =0.025). The no-compression pancreatic dissection method was a simple method for reducing POPF incidence. CONCLUSIONS: The method of quickly dissecting the pancreas without compression yielded better results than the method of slowly dissecting the pancreas with slow compression. This quick dissection without compression was a simple and safe method that minimized postoperative pancreatic fluid leakage, shortened the operative time and length of hospital stay, and reduced medical costs. Therefore, this method might be a clinically successful option.