Resection to Exploration Ratios and Associated Outcomes in Patients with Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: To investigate resection/exploration ratios (RER), reasons for omission of pancreatectomy, and survival outcomes in patients undergoing surgical exploration with resection intent for pancreatic ductal adenocarcinoma (PDAC). SUMMARY BACKGROUND DATA: While surgical indications for PDAC are expanding, information about intraoperative attrition is lacking. METHODS: The RER was calculated in PDAC patients undergoing exploration from 2018 through 2020. Factors associated with uncompleted resection and survival were identified using multivariable models. RESULTS: In total, 681 patients were included. Upfront explorations were 296 (43.7%), and post-neoadjuvant explorations were 385 (56.3%). The overall RER was 89.7% (90.5% in the upfront setting and 89.1% post-neoadjuvant treatment). In this latter subgroup, the RER decreased from 96.1% in resectable disease to 86.6% in borderline resectable disease and 61.9% in locally advanced disease. The primary reasons for uncompleted resection were occult metastases in presumed resectable/borderline resectable disease (without difference between upfront and post-neoadjuvant operations) and local unresectability in locally advanced disease. No preoperative variable was associated with uncompleted resection in upfront explorations, while anatomical staging informed the likelihood of surgical attrition following neoadjuvant treatment. Uncompleted resection was invariably associated with a median survival of around one year. The median post-pancreatectomy survival was 36.9 months in the upfront setting and 29.5 months following neoadjuvant treatment. The median survival from diagnosis in patients receiving post-neoadjuvant resection was 34.5 months. CONCLUSIONS: This analysis provided contemporary information about resection rates, reasons for intraoperative attrition, and survival outcomes in the entire spectrum of PDAC patients selected for surgical exploration at an experienced institution.

Morphologic Characterization of Pancreatic Ductal Adenocarcinoma following Post-neoadjuvant Pancreatectomy and Clinical value of Intratumor Heterogeneity.

OBJECTIVE: To evaluate the morphologic landscape of pancreatic ductal adenocarcinoma (PDAC), intratumor spatial heterogeneity, and the resulting clinical impact following post-neoadjuvant pancreatectomy. SUMMARY BACKGROUND DATA: The clinical value of PDAC morphologic subtypes and intratumor spatial heterogeneity post-treatment remains an open issue. MATERIALS AND METHODS: The study cohort included patients who underwent post-neoadjuvant pancreatectomy for PDAC at the University of Verona Hospital Trust between 2013 and 2019. All hematoxylin and eosin-stained slides were reviewed to assess PDAC histomorphology and intratumor heterogeneity. The relationship with other clinicopathological variables, overall survival (OS), and recurrence-free (RFS) survival was evaluated using standard statistics. RESULTS: The study cohort included 400 patients. Histological revision identified ten different morphologic subtypes. Gland-forming PDAC with a conventional pattern was the most frequently identified subtype (41.8%). Overall, 247 tumors (61.7%) showed only one histological pattern and were classified as homogeneous, whereas 153 (38.3%) showed different morphologies and were classified as heterogeneous tumors. The median post-resection survival was 30.1 months (95%CI 26.6-33.5). There was a substantial survival variability according to the morphologic subtype, ranging from 19.1 months in the gyriform subtype to 47.0 months in the papillary subtype. Tumors with a heterogeneous morphology displayed a higher rate of nodal metastases, worse tumor regression metrics, and worse oncologic outcomes relative to spatially homogeneous tumors. DISCUSSION: This paper provided a morphological taxonomy of residual tumors following post-neoadjuvant pancreatectomy for PDAC. The morphologic subtype and intratumor spatial heterogeneity have relevant prognostic implications and could be included in the pathology report to complement regression metrics.

Adjuvant Therapy After Upfront Resection of Resectable Pancreatic Cancer: Patterns of Omission and Use-A Prospective Real-Life Study.

BACKGROUND: Little is known about adjuvant therapy (AT) omission and use outside of randomized trials. We aimed to assess the patterns of AT omission and use in a cohort of upfront resected pancreatic cancer patients in a real-life scenario. METHODS: From January 2019 to July 2022, 317 patients with resected pancreatic cancer and operated upfront were prospectively enrolled in this prospective observational trial according to the previously calculated sample size. The association between perioperative variables and the risk of AT omission and AT delay was analyzed using multivariable logistic regression. RESULTS: Eighty patients (25.2%) did not receive AT. The main reasons for AT omission were postoperative complications (38.8%), oncologist's choice (21.2%), baseline comorbidities (20%), patient's choice (10%), and early recurrence (10%). At the multivariable analysis, the odds of not receiving AT increased significantly for older patients (odds ratio [OR] 1.1, p < 0.001), those having an American Society of Anesthesiologists score ≥II (OR 2.03, p = 0.015), or developing postoperative pancreatic fistula (OR 2.5, p = 0.019). The likelihood of not receiving FOLFIRINOX as AT increased for older patients (OR 1.1, p < 0.001), in the presence of early-stage disease (stage I-IIa vs. IIb-III, OR 2.82, p =0.031; N0 vs. N+, OR 3, p = 0.03), and for patients who experienced postoperative major complications (OR 4.7, p = 0.009). A twofold increased likelihood of delay in AT was found in patients experiencing postoperative complications (OR 3.86, p = 0.011). CONCLUSIONS: AT is not delivered in about one-quarter of upfront resected pancreatic cancer patients. Age, comorbidities, and postoperative complications are the main drivers of AT omission and mFOLFIRINOX non-use. CLINICALTRIALS REGISTRATION: NCT03788382.

Association of high-risk stigmata and worrisome features with advanced neoplasia in intraductal papillary mucinous neoplasms (IPMN): A systematic review.

BACKGROUND: This systematic review aimed to assess the diagnostic accuracy of the International Consensus Fukuoka Guidelines (ICG2017) in identifying high-risk lesions of Intraductal Papillary Mucinous Neoplasms (IPMNs). METHODS: The ICG2017 revision committee conducted a comprehensive literature review to establish evidence-based statements on IPMNs. The review focused on articles examining the diagnostic value of imaging features (e.g., cyst or main pancreatic duct diameter), clinical symptoms associated with IPMN, and serum biomarkers. Five clinical questions regarding high-risk stigmata (HRS) and worrisome features (WF) in the ICG2017 guidelines were addressed. RESULTS: A total of 210 articles were reviewed. The findings revealed a significant association between the presence of mural nodules ≥5 mm in diameter or solid components with contrast enhancement and the diagnosis of high-grade dysplasia or invasive carcinoma. Contrast-enhanced diagnostic tools, such as CT, MRI, or EUS, demonstrated the highest prediction rate and were recommended. Positive cytology was identified as an HRS, while symptoms like acute pancreatitis and cyst diameter growth ≥2.5 mm per year were considered WFs. The use of nomograms and multiple diagnostic factors was recommended for optimal IPMN management. CONCLUSIONS: This systematic review provides evidence supporting the improved diagnostic accuracy of ICG2017 in identifying high-risk lesions of IPMN. The multidisciplinary incorporation of HRS and WF based on imaging findings and clinical symptoms is crucial. These findings should inform the revision of ICG2017, enhancing the evaluation and management of IPMN patients. By implementing these recommendations, clinicians can make more informed decisions, leading to better diagnosis and treatment outcomes for high-risk IPMN cases.

Diurnal and day-to-day biological variation of salivary cortisol and cortisone.

OBJECTIVES: There is a growing interest in the relevance of salivary cortisol and cortisone concentrations in stress-related research. To correctly attribute the magnitude of salivary cortisol and cortisone variation as an effect of a stressful event, a coherent understanding of the day-to-day intra-individual and inter-individual variability across the diurnal cycle of the two steroids is required. However, such information is currently lacking. METHODS: This study aimed to overcome these existing limitations by performing an investigation of the biological variation (BV) of salivary cortisol and cortisone within one day and between five days using an LC-MS/MS method. Saliva samples were collected from 20 healthy volunteers immediately after waking up, at 8:00, 12:00, 15:00, 19:00 and 23:00 on each day over five days. All samples were analyzed in duplicate in one run. Nested ANOVA was used to calculate the sums of squares for analytical and biological components of variation. RESULTS: The within-subject BV of salivary cortisol and cortisone (CVI) ranged from a minimum of 29.3 and 19.0 % to a maximum of 56.5 and 49.1 %, respectively, while the between-subject biological variation (CVG) ranged from 29.7 and 29.0 % to 51.6 and 43.6 %. The reference change values (RCVs) ranged from 96 to 245 % for cortisol and from 55 to 194 % for cortisone. A medium index of individuality was observed for both compounds at all time points. CONCLUSIONS: This study provides updated BV estimates and RCVs for different times of day that can be used to assess the magnitude of change in biomarkers in future stress-related research.

Nationwide cost-effectiveness and quality of life analysis of minimally invasive distal pancreatectomy.

BACKGROUND: This study analyzed the Quality of Life (QoL) and cost-effectiveness of laparoscopic (LDP) versus robotic distal pancreatectomy (RDP). METHODS: Consecutive patients submitted to LDP or RDP from 2010 to 2020 in four high-volume Italian centers were included, with a minimum of 12 months of postoperative follow-up were included. QoL was evaluated using the EORTC QLQ-C30 and EQ-5D questionnaires, self-reported by patients. After a propensity score matching, which included BMI, gender, operation time, multiorgan and vascular resections, splenic preservation, and pancreatic stump management, the mean differential cost and Quality-Adjusted Life Years (QALY) were calculated and plotted on a cost-utility plane. RESULTS: The study population consisted of 564 patients. Among these, 271 (49%) patients were submitted to LDP, while 293 (51%) patients to RDP. After propensity score matching, the study population was composed of 159 patients in each group, with a median follow-up of 59 months. As regards the QoL analysis, global health and emotional functioning domains showed better results in the RDP group (p = 0.037 and p = 0.026, respectively), whereas the other did not differ. As expected, the median crude costs analysis confirmed that RDP was more expensive than LDP (16,041 Euros vs. 10,335 Euros, p < 0.001). However, the robotic approach had a higher probability of being more cost-effective than the laparoscopic procedure when a willingness to pay more than 5697 Euros/QALY was accepted. CONCLUSION: RDP was associated with better QoL as explored by specific domains. Crude costs were higher for RDP, and the cost-effectiveness threshold was set at 5697 euros/QALY.

Surgical optomics: hyperspectral imaging and deep learning towards precision intraoperative automatic tissue recognition-results from the EX-MACHYNA trial.

BACKGROUND: Hyperspectral imaging (HSI), combined with machine learning, can help to identify characteristic tissue signatures enabling automatic tissue recognition during surgery. This study aims to develop the first HSI-based automatic abdominal tissue recognition with human data in a prospective bi-center setting. METHODS: Data were collected from patients undergoing elective open abdominal surgery at two international tertiary referral hospitals from September 2020 to June 2021. HS images were captured at various time points throughout the surgical procedure. Resulting RGB images were annotated with 13 distinct organ labels. Convolutional Neural Networks (CNNs) were employed for the analysis, with both external and internal validation settings utilized. RESULTS: A total of 169 patients were included, 73 (43.2%) from Strasbourg and 96 (56.8%) from Verona. The internal validation within centers combined patients from both centers into a single cohort, randomly allocated to the training (127 patients, 75.1%, 585 images) and test sets (42 patients, 24.9%, 181 images). This validation setting showed the best performance. The highest true positive rate was achieved for the skin (100%) and the liver (97%). Misclassifications included tissues with a similar embryological origin (omentum and mesentery: 32%) or with overlaying boundaries (liver and hepatic ligament: 22%). The median DICE score for ten tissue classes exceeded 80%. CONCLUSION: To improve automatic surgical scene segmentation and to drive clinical translation, multicenter accurate HSI datasets are essential, but further work is needed to quantify the clinical value of HSI. HSI might be included in a new omics science, namely surgical optomics, which uses light to extract quantifiable tissue features during surgery.

Pancreatic Enucleation Patients Share the Same Quality of Life as the General Population at Long-Term Follow-Up: A Propensity Score-Matched Analysis.

OBJECTIVE: The aim of this study was to assess short- and long-term outcomes including quality of life (QoL) following pancreatic enucleation (PE). BACKGROUND: PE is deemed to preserve both the endocrine and the exocrine function while ensuring radicality. However, to assess whether this reflects an actual benefit perceived by patients, QoL has to be considered. METHODS: Data from all consecutive patients undergoing PE from January 2010 to December 2019 were retrospectively analyzed. Surgical outcomes were graded according to the Clavien-Dindo classification, and EORTC-C30 and the EORTC-Pan26 were administered as a cross-sectional assessment of QoL. A control group consisting of healthy individuals from the general population was obtained and matched using the propensity score matching method. RESULTS: Eighty-one patients underwent PE using the open (59.3%), laparoscopic (27.2%), or robot-assisted (13.5%) approach. Sixty-five (80.2%) patients exhibited functioning/nonfunctioning pancreatic neuroendocrine tumors at final pathology.Surgical morbidity and complications of a Clavien-Dindo grade ≥3 were 48.1% and 16.0%, respectively. In-hospital mortality was 0%. Postoperative pancreatic fistula, post-pancreatectomy hemorrhage, and delayed gastric emptying rates were 21.0%, 9.9%, and 4.9%, respectively.Patients returned the questionnaires after a median of 74.2 months from the index surgery. Postoperative new onset of diabetes mellitus (NODM) was observed in 5 subjects (7.1%), with age being an independent predictor. Seven patients (10.0%) developed postoperative exocrine insufficiency. At the analysis of QoL, all function and symptom scales were comparable between the 2 groups, except for 2 of the EORTC-Pan 26 symptom scales, ("worries for the future" and "body image", P < 0.05). CONCLUSIONS: Despite being associated with significant postoperative morbidity, PE provides excellent long-term outcomes. The risk of NODM is low and related to patient age, with QoL being comparable to the general population. Such information should drive surgeons to pursue PE whenever properly indicated.

Distal Pancreatectomy Fistula Risk Score (D-FRS): Development and International Validation.

OBJECTIVE: To develop 2 distinct preoperative and intraoperative risk scores to predict postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP) to improve preventive and mitigation strategies, respectively. BACKGROUND: POPF remains the most common complication after DP. Despite several known risk factors, an adequate risk model has not been developed yet. METHODS: Two prediction risk scores were designed using data of patients undergoing DP in 2 Italian centers (2014-2016) utilizing multivariable logistic regression. The preoperative score (calculated before surgery) aims to facilitate preventive strategies and the intraoperative score (calculated at the end of surgery) aims to facilitate mitigation strategies. Internal validation was achieved using bootstrapping. These data were pooled with data from 5 centers from the United States and the Netherlands (2007-2016) to assess discrimination and calibration in an internal-external validation procedure. RESULTS: Overall, 1336 patients after DP were included, of whom 291 (22%) developed POPF. The preoperative distal fistula risk score (preoperative D-FRS) included 2 variables: pancreatic neck thickness [odds ratio: 1.14; 95% confidence interval (CI): 1.11-1.17 per mm increase] and pancreatic duct diameter (OR: 1.46; 95% CI: 1.32-1.65 per mm increase). The model performed well with an area under the receiver operating characteristic curve of 0.83 (95% CI: 0.78-0.88) and 0.73 (95% CI: 0.70-0.76) upon internal-external validation. Three risk groups were identified: low risk (<10%), intermediate risk (10%-25%), and high risk (>25%) for POPF with 238 (18%), 684 (51%), and 414 (31%) patients, respectively. The intraoperative risk score (intraoperative D-FRS) added body mass index, pancreatic texture, and operative time as variables with an area under the receiver operating characteristic curve of 0.80 (95% CI: 0.74-0.85). CONCLUSIONS: The preoperative and the intraoperative D-FRS are the first validated risk scores for POPF after DP and are readily available at: http://www.pancreascalculator.com . The 3 distinct risk groups allow for personalized treatment and benchmarking.

Short-term Outcomes After Spleen-preserving Minimally Invasive Distal Pancreatectomy With or Without Preservation of Splenic Vessels: A Pan-European Retrospective Study in High-volume Centers.

OBJECTIVE: To compare short-term clinical outcomes after Kimura and Warshaw MIDP. BACKGROUND: Spleen preservation during distal pancreatectomy can be achieved by either preservation (Kimura) or resection (Warshaw) of the splenic vessels. Multicenter studies reporting outcomes of Kimura and Warshaw spleen-preserving MIDP are scarce. METHODS: Multicenter retrospective study including consecutive MIDP procedures intended to be spleen-preserving from 29 high-volume centers (≥15 distal pancreatectomies annually) in 8 European countries. Primary outcomes were secondary splenectomy for ischemia and major (Clavien-Dindo grade ≥III) complications. Sensitivity analysis assessed the impact of excluding ("rescue") Warshaw procedures which were performed in centers that typically (>75%) performed Kimura MIDP. RESULTS: Overall, 1095 patients after MIDP were included with successful splenic preservation in 878 patients (80%), including 634 Kimura and 244 Warshaw procedures. Rates of clinically relevant splenic ischemia (0.6% vs 1.6%, P = 0.127) and major complications (11.5% vs 14.4%, P = 0.308) did not differ significantly between Kimura and Warshaw MIDP, respectively. Mortality rates were higher after Warshaw MIDP (0.0% vs 1.2%, P = 0.023), and decreased in the sensitivity analysis (0.0% vs 0.6%, P = 0.052). Kimura MIDP was associated with longer operative time (202 vs 184 minutes, P = 0.033) and less blood loss (100 vs 150 mL, P < 0.001) as compared to Warshaw MIDP. Unplanned splenectomy was associated with a higher conversion rate (20.7% vs 5.0%, P < 0.001). CONCLUSIONS: Kimura and Warshaw spleen-preserving MIDP provide equivalent short-term outcomes with low rates of secondary splenectomy and postoperative morbidity. Further analyses of long-term outcomes are needed.

Pancreatic Anastomosis in Robotic-Assisted Pancreaticoduodenectomy: Different Surgical Techniques.

Robot-assisted pancreatoduodenectomy (R-PD) may provide challenges but potential benefits for pancreatic-enteric anastomosis fashioning. Despite numerous trials comparing different pancreatic-enteric anastomosis techniques, an ideal method is still missing. This study aims to describe different management strategies and surgical techniques of standardized pancreatic-enteric anastomoses during an R-PD. This study reported the robotic technical steps of the modified end-to-side Blumgart pancreaticojejunostomy, the Cattel-Warren duct-to-mucosa pancreatojejunostomy, with internal or external pancreatic duct stent, and the modified end-to-side, double-layer pancreogastrostomy. A dual-console da Vinci Xi Surgical System® (Intuitive Surgical Xi, Sunnyvale, CA) was used to perform all the R-PD. Different robotic pancreatic-enteric anastomosis techniques can be used during the reconstruction phase, possibly reproducing the open technique. The type of anastomosis and applied mitigation strategies should balance surgical strategy adaptability and operative technique standardization. R-PD should be performed in high-volume centers by surgeons with extensive experience in pancreatic and advanced MI surgery, enabling different but standardized anastomotic techniques based on patients' risk factors and intraoperative findings. Future studies on robotic pancreatic anastomosis should focus on personalized approaches after adequate risk stratification.

Nationwide validation of the distal fistula risk score (D-FRS).

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.

Pancreatoduodenectomy at the Verona Pancreas Institute: the Evolution of Indications, Surgical Techniques, and Outcomes: A Retrospective Analysis of 3000 Consecutive Cases.

OBJECTIVE: The aim of the present study was to critically reappraise the experience at our high-volume institution to obtain new insights for future directions. SUMMARY BACKGROUND DATA: The indications, surgical techniques, and perioperative management of pancreatoduodenectomy (PD) have profoundly evolved over the last 20 years. METHODS: All consecutive PDs performed during the last 20 years at the Verona Pancreas Institute were divided into four 5-year timeframes and retrospectively analyzed in terms of indications, intraoperative features, and surgical outcomes. Significant milestones were provided to understand practice changes using a before-after analysis method. RESULTS: The study population consisted of 3000 patients. The median age, ASA ≥ 3 and number of nonbenchmark cases significantly increased over time ( P < 0.005). Pancreatic cancer was the leading indication, representing 60% of patients/year in the last timeframe, 40% of whom received neoadjuvant treatment. Conversely, after the development of International Guidelines, the proportion of resected cystic neoplasms progressively and thoroughly decreased. Given the increased complexity of surgery for pancreatic cancer, the evolution of technologies, surgical techniques, and postoperative management allowed the maintenance of favorable surgical outcomes over time, with a stable 20.0% of patients with a Clavien-Dindo grade ≥ 3, an 11.7% failure to rescue and a 2.3% in-hospital mortality rate. The incidence of postoperative pancreatic fistula, hemorrhage, and delayed gastric emptying was 22.4%, 13.4%, and 12.4%, respectively. CONCLUSIONS: PD significantly evolved in Verona over the past 2 decades. Surgeries of greater complexity are currently performed on increasingly frailer patients, mostly for pancreatic cancer and often after neoadjuvant chemotherapy. However, the progression of all fields of pancreatic surgery, including the expanding use of postoperative pancreatic fistula mitigation strategies, has allowed satisfactory outcomes to be maintained.

Prognostic Factors After Pancreatectomy for Pancreatic Cancer Initially Metastatic to the Liver.

BACKGROUND: Resection of initially oligometastatic pancreatic ductal adenocarcinoma (PDAC) following response to first-line chemotherapy is controversial. We herein updated a previous case series to investigate the oncologic outcomes and preoperative factors that could drive the decision-making process. METHODS: This retrospective analysis was limited to patients with liver-only synchronous metastases who experienced complete regression of the metastatic component and underwent pancreatectomy between October 2008 and July 2020 at two high-volume institutions. Clinical-pathologic variables were captured, and inflammation-based prognostic scores were calculated. Recurrence and survival analyses were performed using standard statistical methods. RESULTS: Overall, 52 patients were included. FOLFIRINOX was the most employed chemotherapy regimen (63.5%). Post-treatment tumor size, serum carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) were significantly decreased relative to baseline evaluation. The median time from diagnosis to pancreatectomy was 10.2 months, while the median time from chemotherapy completion to pancreatectomy was 2 months. Major postoperative complications occurred in 26.9% of patients, while postoperative mortality was nil. The median disease-free survival (DFS) and overall survival (OS) from pancreatectomy were 16.5 and 23.0 months, respectively, and the median OS from diagnosis was 37.2 months. At multivariable analysis, vascular resection, operative time, prognostic nutrition index (PNI) and neutrophil-to-lymphocyte ratio (NLR) were associated with OS. Operative time, platelet × neutrophil/lymphocyte count (SII), and PNI were associated with DFS. CONCLUSIONS: We confirm promising outcomes of selected patients who underwent pancreatectomy following downstaging of liver metastases. The absence of vascular involvement of the primary tumor, good nutritional status, and low inflammatory index scores could be useful to select candidates for resection.

Benchmarking of robotic and laparoscopic spleen-preserving distal pancreatectomy by using two different methods.

BACKGROUND: Benchmarking is an important tool for quality comparison and improvement. However, no benchmark values are available for minimally invasive spleen-preserving distal pancreatectomy, either laparoscopically or robotically assisted. The aim of this study was to establish benchmarks for these techniques using two different methods. METHODS: Data from patients undergoing laparoscopically or robotically assisted spleen-preserving distal pancreatectomy were extracted from a multicentre database (2006-2019). Benchmarks for 10 outcomes were calculated using the Achievable Benchmark of Care (ABC) and best-patient-in-best-centre methods. RESULTS: Overall, 951 laparoscopically assisted (77.3 per cent) and 279 robotically assisted (22.7 per cent) procedures were included. Using the ABC method, the benchmarks for laparoscopically assisted and robotically assisted spleen-preserving distal pancreatectomy respectively were: 150 and 207 min for duration of operation, 55 and 100 ml for blood loss, 3.5 and 1.7 per cent for conversion, 0 and 1.7 per cent for failure to preserve the spleen, 27.3 and 34.0 per cent for overall morbidity, 5.1 and 3.3 per cent for major morbidity, 3.6 and 7.1 per cent for pancreatic fistula grade B/C, 5 and 6 days for duration of hospital stay, 2.9 and 5.4 per cent for readmissions, and 0 and 0 per cent for 90-day mortality. Best-patient-in-best-centre methodology revealed milder benchmark cut-offs for laparoscopically and robotically assisted procedures, with operating times of 254 and 262.5 min, blood loss of 150 and 195 ml, conversion rates of 5.8 and 8.2 per cent, rates of failure to salvage spleen of 29.9 and 27.3 per cent, overall morbidity rates of 62.7 and 55.7 per cent, major morbidity rates of 20.4 and 14 per cent, POPF B/C rates of 23.8 and 24.2 per cent, duration of hospital stay of 8 and 8 days, readmission rates of 20 and 15.1 per cent, and 90-day mortality rates of 0 and 0 per cent respectively. CONCLUSION: Two benchmark methods for minimally invasive distal pancreatectomy produced different values, and should be interpreted and applied differently.

Benchmarking of minimally invasive distal pancreatectomy with splenectomy: European multicentre study.

BACKGROUND: Benchmarking is the process to used assess the best achievable results and compare outcomes with that standard. This study aimed to assess best achievable outcomes in minimally invasive distal pancreatectomy with splenectomy (MIDPS). METHODS: This retrospective study included consecutive patients undergoing MIDPS for any indication, between 2003 and 2019, in 31 European centres. Benchmarks of the main clinical outcomes were calculated according to the Achievable Benchmark of Care (ABC™) method. After identifying independent risk factors for severe morbidity and conversion, risk-adjusted ABCs were calculated for each subgroup of patients at risk. RESULTS: A total of 1595 patients were included. The ABC was 2.5 per cent for conversion and 8.4 per cent for severe morbidity. ABC values were 160 min for duration of operation time, 8.3 per cent for POPF, 1.8 per cent for reoperation, and 0 per cent for mortality. Multivariable analysis showed that conversion was associated with male sex (OR 1.48), BMI exceeding 30 kg/m2 (OR 2.42), multivisceral resection (OR 3.04), and laparoscopy (OR 2.24). Increased risk of severe morbidity was associated with ASA fitness grade above II (OR 1.60), multivisceral resection (OR 1.88), and robotic approach (OR 1.87). CONCLUSION: The benchmark values obtained using the ABC method represent optimal outcomes from best achievable care, including low complication rates and zero mortality. These benchmarks should be used to set standards to improve patient outcomes.

Routine prophylactic abdominal drainage versus no-drain strategy after distal pancreatectomy: A multicenter propensity score matched analysis.

BACKGROUND: /Objectives Postoperative pancreatic fistula (POPF) remains the most common complication after distal pancreatectomy (DP). Traditionally, surgical drains are placed routinely after DP, but some question its efficacy and postulate that the use of drains may convert a self-limiting postoperative collection into a POPF. This study aimed to compare outcomes between three institutions with varying drainage strategies. METHODS: The study is a retrospective propensity score-matched analysis of intraoperative prophylactic drain placement during DP (2010-2019). The primary outcome is major morbidity. Propensity score matching was used to obtain comparable groups. RESULTS: Overall, 963 patients after DP were included. One center did not place a surgical drain routinely, but decided to place a drain when unsatisfactory pancreatic closure occurred. Prophylactic abdominal drains were placed in 805 patients (84%) of which 74 could be matched to 74 patients without a drain. The rate of major morbidity (8% vs 19%, p = 0.054) and radiological interventions (5% vs 12%, p = 0.147) were non-significantly lower in the no-drain group as compared to the prophylactic drain group, respectively. The rates of POPF (4% vs 16%, p = 0.014) were lower in the no-drain group. CONCLUSION: In this international retrospective multicenter study, a selective no-drain strategy after DP was not associated with higher rates major morbidity or radiological interventions as compared to routine prophylactic abdominal drainage. Although the rate of POPF was lower in the no-drain group, randomized trials should confirm the safety and outcome of a no-drain strategy after DP.

401 consecutive minimally invasive distal pancreatectomies: lessons learned from 20 years of experience.

BACKGROUND: This study aimed to discuss and report the trend, outcomes, and learning curve effect after minimally invasive distal pancreatectomy (MIDP) at two high-volume centres. METHODS: Patients undergoing MIDP between January 1999 and December 2018 were retrospectively identified from prospectively maintained electronic databases. The entire cohort was divided into two groups constituting the "early" and "recent" phases. The learning curve effect was analyzed for laparoscopic (LDP) and robotic distal pancreatectomy (RDP). The follow-up was at least 2 years. RESULTS: The study population included 401 consecutive patients (LDP n = 300, RDP n = 101). Twelve surgeons performed MIDP during the study period. Although patients were more carefully selected in the early phase, in terms of median age (49 vs. 55 years, p = 0.026), ASA class higher than 2 (3% vs. 9%, p = 0.018), previous abdominal surgery (10% vs. 34%, p < 0.001), and pancreatic adenocarcinoma (PDAC) (7% vs. 15%, p = 0.017), the recent phase had similar perioperative outcomes. The increase of experience in LDP was inversely associated with the operative time (240 vs 210 min, p < 0.001), morbidity rate (56.5% vs. 40.1%, p = 0.005), intra-abdominal collection (28.3% vs. 17.3%, p = 0.023), and length of stay (8 vs. 7 days, p = 0.009). Median survival in the PDAC subgroup was 53 months. CONCLUSION: In the setting of high-volume centres, the surgical training of MIDP is associated with acceptable rates of morbidity. The learning curve can be largely achieved by several team members, improving outcomes over time. Whenever possible resection of PDAC guarantees adequate oncological results and survival.

A randomized controlled trial of stapled versus ultrasonic transection in distal pancreatectomy.

BACKGROUND: The pancreatic transection method during distal pancreatectomy is thought to influence postoperative fistula rates. Yet, the optimal technique for minimizing fistula occurrence is still unclear. The present randomized controlled trial compared stapled versus ultrasonic transection in elective distal pancreatectomy. METHODS: Patients undergoing distal pancreatectomy from July 2018 to July 2020 at two high-volume institutions were considered for inclusion. Exclusion criteria were contiguous organ resection and a parenchymal thickness > 17 mm on intraoperative ultrasound. Eligible patients were randomized in a 1:1 ratio to stapled transection (Endo GIA Reinforced Reload with Tri-Staple Technology®) or ultrasonic transection (Harmonic Focus® + or Harmonic Ace® + shears). The primary endpoint was postoperative pancreatic fistula. Secondary endpoints included overall complications, abdominal collections, and length of hospital stay. RESULTS: Overall, 72 patients were randomized in the stapled transection arm and 73 patients in the ultrasonic transection arm. Postoperative pancreatic fistula occurred in 23 patients (16%), with a comparable incidence between groups (12% in stapled transection versus 19% in ultrasonic dissection arm, p = 0.191). Overall complications did not differ substantially (35% in stapled transection versus 44% in ultrasonic transection arm, p = 0.170). There was an increased incidence of abdominal collections in the ultrasonic dissection group (32% versus 14%, p = 0.009), yet the need for percutaneous drain did not differ between randomization arms (p = 0.169). The median length of stay was 8 days in both groups (p = 0.880). Intraoperative blood transfusion was the only factor independently associated with postoperative pancreatic fistula on logistic regression analysis (OR 4.8, 95% CI 1.2-20.0, p = 0.032). CONCLUSION: The present randomized controlled trial of stapled versus ultrasonic transection in elective distal pancreatectomy demonstrated no significant difference in postoperative pancreatic fistula rates and no substantial clinical impact on other secondary endpoints.

Modified Frailty Index to Assess Risk in Elderly Patients Undergoing Distal Pancreatectomy: A Retrospective Single-Center Study.

BACKGROUND: To compare the postoperative course of elderly patients (≥70 years) submitted to minimally invasive (MIDP) versus open distal pancreatectomy (ODP) and to evaluate if the modified Frailty Index (mFI) predicts the surgical course of elderly patients submitted to DP. METHODS: Data of patients aged ≥70 who underwent DP at a single institution between March 2011 and December 2019 were retrospectively retrieved. A 2:1 propensity score matching (PSM) was used to correct for differences in baseline characteristics. Then, postoperative complications were compared between the two groups (MIDP vs. ODP). Additionally, the entire cohort of DP elderly patients was stratified according to the mFI into three groups: non-frail (mFI = 0), mildly frail (mFI = 1/2), or severely frail (mFI = 3) and then compared. RESULTS: A total of 204 patients were analyzed. After PSM, 40 MIDP and 80 ODP patients were identified. The complications considered stratified homogenously between the two groups, with no statistically significant differences. The severity of the postoperative course increased as mFI did among the three groups regarding any complication (p = 0.022), abdominal collection (p = 0.014), pulmonary complication (p = 0.001), postoperative confusion (p = 0.047), Clavien-Dindo severity ≥3 events (p = 0.036), and length of stay (p = 0.018). CONCLUSIONS: Elderly patients can be safely submitted to MIDP. The mFI identifies frail elderly patients more prone to develop surgical and non-surgical complications after DP.