Complexity and Experience Grading to Guide Patient Selection for Minimally-invasive Pancreatoduodenectomy: An ISGPS Consensus.

OBJECTIVE: The ISGPS aims to develop a universally accepted complexity and experience grading system to guide the safe implementation of robotic and laparoscopic minimally-invasive pancreatoduodenectomy (MIPD). BACKGROUND: Despite the perceived advantages of MIPD, its global adoption has been slow due to the inherent complexity of the procedure and challenges to acquiring surgical experience. Its wider adoption must be undertaken with an emphasis towards appropriate patient selection according to adequate surgeon and center experience. METHODS: The ISGPS developed a complexity and experience grading system to guide patient selection for MIPD based on an evidence-based review and a series of discussions. RESULTS: The ISGPS complexity and experience grading system for MIPD is subclassified into patient-related risk factors and provider experience-related variables. The patient-related risk factors include anatomical (main pancreatic and common bile duct diameters), tumor-specific (vascular contact), and conditional (obesity and previous complicated upper abdominal surgery/disease) factors, all incorporated in an A-B-C classification, graded as no, a single, and multiple risk factors. The surgeon and center experience-related variables include surgeon total MIPD experience (cut-offs 40 and 80) and center annual MIPD volume (cut-offs 10 and 30), all also incorporated in an A-B-C classification. CONCLUSION: This ISGPS complexity and experience grading system for robotic and laparoscopic MIPD may enable surgeons to optimally select patients after duly considering specific risk factors known to influence the complexity of the procedure. This grading system will likely allow for a thoughtful and stepwise implementation of MIPD and facilitate a fair comparison of outcome between centers and countries.

REDISCOVER International Guidelines on the Perioperative Care of Surgical Patients With Borderline-resectable and Locally Advanced Pancreatic Cancer.

OBJECTIVE: The REDISCOVER consensus conference aimed at developing and validating guidelines on the perioperative care of patients with borderline-resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports the resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking. METHODS: The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach a consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to nonsurgical guidelines. RESULTS: Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis, and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive means to promptly advance our understanding in this field is to establish an international registry addressing this patient population ( https://rediscover.unipi.it/ ). CONCLUSIONS: The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR-PDAC and LA-PDAC, and serve as the basis of a new international registry for this patient population.

Outcomes of a 3-Year Prospective Surveillance in Individuals at High Risk of Pancreatic Cancer.

INTRODUCTION: Pancreatic cancer (PC) surveillance of high-risk individuals (HRI) is becoming more common worldwide, aiming at anticipating PC diagnosis at a preclinical stage. In 2015, the Italian Registry of Families at Risk of Pancreatic Cancer was created. We aimed to assess the prevalence and incidence of pancreatic findings, oncological outcomes, and harms 7 years after the Italian Registry of Families at Risk of Pancreatic Cancer inception, focusing on individuals with at least a 3-year follow-up or developing events before. METHODS: HRI (subjects with a family history or mutation carriers with/without a family history were enrolled in 18 centers). They underwent annual magnetic resonance with cholangiopancreatography or endoscopic ultrasound (NCT04095195). RESULTS: During the study period (June 2015-September 2022), 679 individuals were enrolled. Of these, 524 (77.2%) underwent at least baseline imaging, and 156 (29.8%) with at least a 3-year follow-up or pancreatic malignancy/premalignancy-related events, and represented the study population. The median age was 51 (interquartile range 16) years. Familial PC cases accounted for 81.4% of HRI and individuals with pathogenic variant for 18.6%. Malignant (n = 8) and premalignant (1 PanIN3) lesions were found in 9 individuals. Five of these 8 cases occurred in pathogenic variant carriers, 4 in familial PC cases (2 tested negative at germline testing and 2 others were not tested). Three of the 8 PC were stage I. Five of the 8 PC were resectable, 3 Stage I, all advanced cases being prevalent. The 1-, 2-, and 3-year cumulative hazard of PC was 1.7%, 2.5%, and 3%, respectively. Median overall and disease-free survival of patients with resected PC were 18 and 12 months (95% CI not computable). Considering HRI who underwent baseline imaging, 6 pancreatic neuroendocrine neoplasms (1 resected) and 1 low-yield surgery (low-grade mixed-intraductal papillary mucinous neoplasm) were also reported. DISCUSSION: PC surveillance in a fully public health care system is feasible and safe, and leads to early PC or premalignant lesions diagnoses, mostly at baseline but also over time.

Neoadjuvant 177Lu-DOTATATE for non-functioning pancreatic neuroendocrine tumours (NEOLUPANET): multicentre phase II study.

BACKGROUND: Resection of non-functioning pancreatic neuroendocrine tumours (NF-PanNETs) is curative in most patients. The potential benefits of neoadjuvant treatments have, however, never been explored. The primary aim of this study was to evaluate the safety of neoadjuvant 177Lu-labelled DOTA0-octreotate (177Lu-DOTATATE) followed by surgery in patients with NF-PanNETs. METHODS: NEOLUPANET was a multicentre, single-arm, phase II trial of patients with sporadic, resectable or potentially resectable NF-PanNETs at high-risk of recurrence; those with positive 68Ga-labelled DOTA PET were eligible. All patients were candidates for neoadjuvant 177Lu-DOTATATE followed by surgery. A sample size of 30 patients was calculated to test postoperative complication rates against predefined cut-offs. The primary endpoint was safety, reflected by postoperative morbidity and mortality within 90 days. Secondary endpoints included rate of objective radiological response and quality of life. RESULTS: From March 2020 to February 2023, 31 patients were enrolled, of whom 26 completed 4 cycles of 177Lu-DOTATATE. A partial radiological response was observed in 18 of 31 patients, and 13 patients had stable disease. Disease progression was not observed. Twenty-four R0 resections and 4 R1 resections were performed in 29 patients who underwent surgery. One tumour was unresectable owing to vascular involvement. There was no postoperative death. Postoperative complications occurred in 21 of 29 patients. Severe complications were observed in seven patients. Quality of life remained stable after 177Lu-DOTATATE and decreased after surgery. CONCLUSION: Neoadjuvant treatment with 177Lu-DOTATATE is safe and effective for patients with NF-PanNETs.

Surgical removal of non-functioning pancreatic neuroendocrine tumours (NF-PanNETs) can often cure patients. However, it is not known whether treating patients before surgery provides additional benefits. The main aim of the study was to investigate safety of treatment called peptide receptor radionuclide therapy with 177Lu-labelled DOTA0-octreotate (177Lu-DOTATATE) before surgery in patients with NF-PanNETs. The NEOLUPANET study was conducted from March 2020 to February 2023 across multiple centres. Patients with NF-PanNETs that were at high risk of recurrence after surgery were included. All patients received 177Lu-DOTATATE before surgery. The main measure of success was safety, reflected by complications or death within 90 days after surgery. The study enrolled 31 patients and 26 completed four cycles of 177Lu-DOTATATE. Tumours shrank partially in 18 patients, and in 13 patients the tumour remained the same. No tumours increased in size. The entire tumour was removed in 28 of 29 patients. No patients died, but 72% had some complications (severe in 7 patients). The study found that using 177Lu-DOTATATE before surgery is safe and useful for treating patients with NF-PanNETs.

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.

Conversion to open surgery in obese patients undergoing minimally invasive distal pancreatectomy: results from a multicenter analysis.

BACKGROUND: Although minimally invasive distal pancreatectomy (MIDP) is considered a standard approach it still presents a non-negligible rate of conversion to open that is mainly related to some difficulty factors, as obesity. The aim of this study is to analyze the preoperative factors associated with conversion in obese patients with MIDP. METHODS: In this multicenter study, all obese patients who underwent MIDP at 18 international expert centers were included. The preoperative factors associated with conversion to open surgery were analyzed. RESULTS: Out of 436 patients, 91 (20.9%) underwent conversion to open, presenting higher blood loss, longer operative time and similar rate of major complications. Twenty (22%) patients received emergent conversion. At univariate analysis, the type of approach, radiological invasion of adjacent organs, preoperative enlarged lymphnodes and ASA ≥ III were significantly associated with conversion to open. At multivariate analysis, robotic approach showed a significantly lower conversion rate (14.6 % vs 27.3%, OR = 2.380, p = 0.001). ASA ≥ III (OR = 2.391, p = 0.002) and preoperative enlarged lymphnodes (OR = 3.836, p = 0.003) were also independently associated with conversion. CONCLUSION: Conversion rate is significantly lower in patients undergoing robotic approach. Radiological enlarged lymphnodes and ASA ≥ III are also associated with conversion to open. Conversion is associated with poorer perioperative outcomes, especially in case of intraoperative hemorrhage.

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.

Robot-Assisted Versus Laparoscopic Distal Pancreatectomy in Patients with Resectable Pancreatic Cancer: An International, Retrospective, Cohort Study.

BACKGROUND: Robot-assisted distal pancreatectomy (RDP) is increasingly used as an alternative to laparoscopic distal pancreatectomy (LDP) in patients with resectable pancreatic cancer but comparative multicenter studies confirming the safety and efficacy of RDP are lacking. METHODS: An international, multicenter, retrospective, cohort study, including consecutive patients undergoing RDP and LDP for resectable pancreatic cancer in 33 experienced centers from 11 countries (2010-2019). The primary outcome was R0-resection. Secondary outcomes included lymph node yield, major complications, conversion rate, and overall survival. RESULTS: In total, 542 patients after minimally invasive distal pancreatectomy were included: 103 RDP (19%) and 439 LDP (81%). The R0-resection rate was comparable (75.7% RDP vs. 69.3% LDP, p = 0.404). RDP was associated with longer operative time (290 vs. 240 min, p < 0.001), more vascular resections (7.6% vs. 2.7%, p = 0.030), lower conversion rate (4.9% vs. 17.3%, p = 0.001), more major complications (26.2% vs. 16.3%, p = 0.019), improved lymph node yield (18 vs. 16, p = 0.021), and longer hospital stay (10 vs. 8 days, p = 0.001). The 90-day mortality (1.9% vs. 0.7%, p = 0.268) and overall survival (median 28 vs. 31 months, p = 0.599) did not differ significantly between RDP and LDP, respectively. CONCLUSIONS: In selected patients with resectable pancreatic cancer, RDP and LDP provide a comparable R0-resection rate and overall survival in experienced centers. Although the lymph node yield and conversion rate appeared favorable after RDP, LDP was associated with shorter operating time, less major complications, and shorter hospital stay. The specific benefits associated with each approach should be confirmed by multicenter, randomized trials.

Surgical and Oncological Outcomes After Preoperative FOLFIRINOX Chemotherapy in Resected Pancreatic Cancer: An International Multicenter Cohort Study.

BACKGROUND: Preoperative FOLFIRINOX chemotherapy is increasingly administered to patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) to improve overall survival (OS). Multicenter studies reporting on the impact from the number of preoperative cycles and the use of adjuvant chemotherapy in relation to outcomes in this setting are lacking. This study aimed to assess the outcome of pancreatectomy after preoperative FOLFIRINOX, including predictors of OS. METHODS: This international multicenter retrospective cohort study included patients from 31 centers in 19 European countries and the United States undergoing pancreatectomy after preoperative FOLFIRINOX chemotherapy (2012-2016). The primary end point was OS from diagnosis. Survival was assessed using Kaplan-Meier analysis and Cox regression. RESULTS: The study included 423 patients who underwent pancreatectomy after a median of six (IQR 5-8) preoperative cycles of FOLFIRINOX. Postoperative major morbidity occurred for 88 (20.8%) patients and 90-day mortality for 12 (2.8%) patients. An R0 resection was achieved for 243 (57.4%) patients, and 259 (61.2%) patients received adjuvant chemotherapy. The median OS was 38 months (95% confidence interval [CI] 34-42 months) for BRPC and 33 months (95% CI 27-45 months) for LAPC. Overall survival was significantly associated with R0 resection (hazard ratio [HR] 1.63; 95% CI 1.20-2.20) and tumor differentiation (HR 1.43; 95% CI 1.08-1.91). Neither the number of preoperative chemotherapy cycles nor the use adjuvant chemotherapy was associated with OS. CONCLUSIONS: This international multicenter study found that pancreatectomy after FOLFIRINOX chemotherapy is associated with favorable outcomes for patients with BRPC and those with LAPC. Future studies should confirm that the number of neoadjuvant cycles and the use adjuvant chemotherapy have no relation to OS after resection.

Prognostic value of major pathological response following neoadjuvant therapy for non resectable pancreatic ductal adenocarcinoma.

BACKGROUND: The aim of this study is to evaluate the impact of major pathological response on overall survival (OS) in borderline resectable and locally advanced pancreatic ductal adenocarcinoma following neoadjuvant treatment, and to identify predictors of major pathological response. METHODS: Patients surgically resected following neoadjuvant treatment between 2010 and 2020 at the Pederzoli Hospital were retrospectively analyzed. Pathologic response was assessed using the College of American Pathologists (CAP) score, and major pathological response was defined as CAP 0-1. OS was estimated and compared using the Kaplan-Meier method and log-rank test. A logistic and Cox regression model were performed to identify predictors of major pathologic response and OS. RESULTS: Overall, 200 patients were included in the study. A major and complete pathological response were observed in 52(26.0%) and 15(7.3%) patients respectively. The 1-, 3-, 5-year OS was 92.7, 67.2, and 41.7%, and 71.0, 37.4, and 20.8% in patients with or without major pathologic response respectively (log-rank test p < 0.001). Major pathologic response was confirmed as independent predictor of OS (OR 0.50 95%CI 0.29-0.88, p = 0.01). Post-treatment CA19-9 normalization (OR 4.20 95%CI 1.14-10.35, p = 0.02) and radiological post-treatment tumor residual size<25 mm (OR 2.71 95%CI 1.27-5.79, p = 0.01) were found to be independent predictors of major pathologic response. CONCLUSION: Patients experienced a major pathological response after neoadjuvant treatment have an increased survival, and major pathologic response is an independent predictor of OS. A normal CA19-9 value and radiological tumor size at restaging are confirmed to be independent predictors of major pathologic response.

Robotic versus laparoscopic distal pancreatectomy in obese patients.

BACKGROUND: Although robotic distal pancreatectomy (RDP) has a lower conversion rate to open surgery and causes less blood loss than laparoscopic distal pancreatectomy (LDP), clear evidence on the impact of the surgical approach on morbidity is lacking. Prior studies have shown a higher rate of complications among obese patients undergoing pancreatectomy. The primary aim of this study is to compare short-term outcomes of RDP vs. LDP in patients with a BMI ≥ 30. METHODS: In this multicenter study, all obese patients who underwent RDP or LDP for any indication between 2012 and 2022 at 18 international expert centers were included. The baseline characteristics underwent inverse probability treatment weighting to minimize allocation bias. RESULTS: Of 446 patients, 219 (50.2%) patients underwent RDP. The median age was 60 years, the median BMI was 33 (31-36), and the preoperative diagnosis was ductal adenocarcinoma in 21% of cases. The conversion rate was 19.9%, the overall complication rate was 57.8%, and the 90-day mortality rate was 0.7% (3 patients). RDP was associated with a lower complication rate (OR 0.68, 95% CI 0.52-0.89; p = 0.005), less blood loss (150 vs. 200 ml; p < 0.001), fewer blood transfusion requirements (OR 0.28, 95% CI 0.15-0.50; p < 0.001) and a lower Comprehensive Complications Index (8.7 vs. 8.9, p < 0.001) than LPD. RPD had a lower conversion rate (OR 0.27, 95% CI 0.19-0.39; p < 0.001) and achieved better spleen preservation rate (OR 1.96, 95% CI 1.13-3.39; p = 0.016) than LPD. CONCLUSIONS: In obese patients, RDP is associated with a lower conversion rate, fewer complications and better short-term outcomes than LPD.

Hepatic Artery Anomalies in Pancreaticoduodenectomy: Outcomes from a High-Volume Center.

INTRODUCTION: Hepatic artery anomalies (HAA) may have an impact on surgical and oncological outcomes of patients undergoing pancreaticoduodenectomy (PD). METHODS: Patients who underwent PD at our institution between July 2015 and January 2020 were retrospectively reviewed and classified into two groups: group 1, with presence of HAA, and group 2, with no HAA. A weighted logistic regression model was employed to assess the association between HAA and postoperative complications, and to assess the association between HAA and R status in patients with pancreatic cancer. RESULTS: 502 patients were considered for analysis, with 75 (15%) of them in group 1. They had either an accessory (n = 28, 40.8%) or replaced (n = 26, 36.6%) right hepatic artery. Most patients underwent surgery for a malignancy (n = 451; 90%); among them, vascular resection was performed in 69 cases (15%). The presence of a HAA was reported at preoperative imaging only in 4 cases (5%) and the aberrant vessel was preserved in 72% of patients. At weighted multivariable logistic regression analysis, HAA were not associated to higher odds of morbidity (odds ratio [OR]: 0.753, 95% confidence interval [CI]: 0.543-1.043) nor to R1 status in case of pancreatic cancer (OR: 1.583, 95% CI: 0.979-2.561). CONCLUSION: At our institution, the presence of HAA does not have an impact on postoperative outcomes or affects oncological clearance after PD. Hospitals', surgeons', volume and systematic review of preoperative imaging are all factors that help reduce possible adverse events.

Telemedicine and Pancreatic Cancer: A Systematic Review.

Introduction: Pancreatic cancer requires a multidisciplinary approach in a high-volume center for all the steps of the diagnostic-therapeutic course. However, the most experienced centers are not evenly distributed throughout the country causing a real "health migration" that involves patients and families with relevant economic, time, and energy costs to bear. The COVID-19 pandemic had a deep impact on surgical and oncological care and the travel limits due to COVID-related restrictions, have delayed the care of cancer patient living far from the referral centers. In this scenario, several telemedicine approaches have been proposed to reduce the distance between clinicians and patients and to allow a fast and effective access to care even for patients distant from referral centers. The aim of the study is to analyze the evidence and describe the current utility of telemedicine tool for patients with pancreatic cancer. Methods: We systematically searched the literature in the following databases: Web of Science, PubMed, Scopus, and MEDLINE. The inclusion criteria were article describing a telemedicine intervention (virtual visits, telephone follow-up/counseling, mobile or online apps, telemonitoring) and focusing on adult patients with pancreatic cancer at any stage of the disease. Results: In total, 846 titles/abstracts were identified. Following quality assessment, the review included 40 studies. Telemedicine has been proposed in multiple clinical settings, demonstrating high levels of patient and health professional satisfaction. Conclusion: Successful telemedicine applications in patients with pancreatic cancer are telerehabilitation and nutritional assessment, remote symptom control, teledischarge after pancreatic surgery, tele-education and medical mentoring regarding pancreatic disease as well as telepathology.

Treatment characteristics and outcomes of pure Acinar cell carcinoma of the pancreas - A multicentric European study on radically resected patients.

BACKGROUND: Acinar cell carcinomas (ACC) belong to the exocrine pancreatic malignancies. Due to their rarity, there is no consensus regarding treatment strategies for resectable ACC. METHODS: This is a retrospective multicentric study of radically resected pure pancreatic ACC. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Further endpoints were oncologic outcomes related to tumor stage and therapeutic protocols. RESULTS: 59 patients (44 men) with a median age of 64 years were included. The median tumor size was 45.0 mm. 61.0% were pT3 (n = 36), nodal positivity rate was 37.3% (n = 22), and synchronous distant metastases were present in 10.1% of the patients (n = 6). 5-Years OS was 60.9% and median DFS 30 months. 24 out of 31 recurred systemically (n = 18 only systemic, n = 6 local and systemic). Regarding TNM-staging, only the N2-stage negatively influenced OS and DFS (p = 0.004, p = 0.001). Adjuvant treatment protocols (performed in 62.7%) did neither improve OS (p = 0.542) nor DFS (p = 0.159). In 9 cases, radical resection was achieved following neoadjuvant therapy. DISCUSSION: Radical surgery is currently the mainstay for resectable ACC, even for limited metastatic disease. Novel (neo)adjuvant treatment strategies are needed, since current systemic therapies do not result in a clear survival benefit in the perioperative setting.

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.

Clinical Outcomes After Total Pancreatectomy: A Prospective Multicenter Pan-European Snapshot Study.

OBJECTIVE: To assess outcomes among patients undergoing total pancreatectomy (TP) including predictors for complications and in-hospital mortality. BACKGROUND: Current studies on TP mostly originate from high-volume centers and span long time periods and therefore may not reflect daily practice. METHODS: This prospective pan-European snapshot study included patients who underwent elective (primary or completion) TP in 43 centers in 16 European countries (June 2018-June 2019). Subgroup analysis included cutoff values for annual volume of pancreatoduodenectomies (<60 vs ≥60).Predictors for major complications and in-hospital mortality were assessed in multivariable logistic regression. RESULTS: In total, 277 patients underwent TP, mostly for malignant disease (73%). Major postoperative complications occurred in 70 patients (25%). Median hospital stay was 12 days (IQR 9-18) and 40 patients were readmitted (15%). In-hospital mortality was 5% and 90-day mortality 8%. In the subgroup analysis, in-hospital mortality was lower in patients operated in centers with ≥60 pancreatoduodenectomies compared <60 (4% vs 10%, P = 0.046). In multivariable analysis, annual volume <60 pancreatoduodenectomies (OR 3.78, 95% CI 1.18-12.16, P = 0.026), age (OR 1.07, 95% CI 1.01-1.14, P = 0.046), and estimated blood loss ≥2L (OR 11.89, 95% CI 2.64-53.61, P = 0.001) were associated with in-hospital mortality. ASA ≥3 (OR 2.87, 95% CI 1.56-5.26, P = 0.001) and estimated blood loss ≥2L (OR 3.52, 95% CI 1.25-9.90, P = 0.017) were associated with major complications. CONCLUSION: This pan-European prospective snapshot study found a 5% inhospital mortality after TP. The identified predictors for mortality, including low-volume centers, age, and increased blood loss, may be used to improve outcomes.

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.

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.