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.

Perioperative NALIRIFOX in patients with resectable pancreatic ductal adenocarcinoma: The open-label, multicenter, phase II nITRO trial.

BACKGROUND: Upfront surgery followed by postoperative treatment is a commonly adopted treatment for resectable pancreatic ductal adenocarcinoma (rPDAC). However, the risk of positive surgical margins, the poor recovery that often impairs postoperative treatments, and the risk of recurrence might limit the outcome of this strategy. This study evaluated the safety and the activity of liposomal irinotecan 50 mg/m2 + 5-fluorouracil 2400 mg/m2 + leucovorin 400 mg/m2 + oxaliplatin 60 mg/m2 (NALIRIFOX) in the perioperative treatment of patients with rPDAC. METHODS: Eligible patients had a rPDAC with < 180° interface with major veins' wall. Patients received 3 cycles before and 3 cycles after resection with NALIRIFOX, days 1 and 15 of a 28-day cycle. The primary endpoint was the proportion of patients undergoing an R0 resection. RESULTS: 107 patients began preoperative treatment. Nine patients discontinued the treatment because of related or unrelated adverse events. Disease-control rate was 92.9%. 87 patients underwent surgical exploration, 11 had intraoperative evidence of metastatic disease, and 1 died for surgical complications. R0 resection rate was 65.3%. 49 patients completed the three postoperative cycles. The most common grade ≥ 3 adverse events were diarrhea and neutropenia. Median overall survival (OS) of ITT patients was 32.3 months (95% CI 27.8-44.3). Median disease-free and OS from surgery of resected patients were 19.3 (95% CI 12.6-34.1) and 40.3 months (95% CI 29-NA), respectively. CONCLUSION: Perioperative NALIRIFOX was manageable and active, and deserves further investigation in randomized trials comparing it with standard upfront surgery followed by adjuvant therapy.

A dynamic analysis of empirical survival outcomes after pancreatectomy for pancreatic ductal adenocarcinoma.

BACKGROUND: Survival outcomes after pancreatectomy for pancreatic ductal adenocarcinoma may be biased by right-censoring. We herein analyzed a large dataset with no censored events for up to 5 years and dynamically investigated the impact of known prognostic factors, accounting for unobserved tumor characteristics. METHODS: Consecutive patients undergoing pancreatectomy from 2000 to July 2015 were included. The 1- to 5-year empirical survival rates were calculated, and factors associated with long-term survival (≥5 years) were analyzed using multivariable models. Dynamic analyses of survival and recurrence were conducted through landmarking, and the contribution of unobserved heterogeneity was estimated using frailty models. RESULTS: The study population included 1,048 patients. The median follow-up was 30.4 months in the whole cohort and 97.2 months in survivors. The median survival was 30.4 months, with empirical 1- to 5-year rates of 85.5%, 59.6%, 43.2%, 32.1%, and 27.5%. A favorable pathological profile was associated with 5-year survival, albeit 25.7% of long-survivors received an R1 resection, and 28.8% had N2 disease. The median recurrence-free survival was 17.2 months. At landmark analyses, baseline prognostic lost strength over time, with no independent predictors of survival being identified in the sets of patients alive at 4 and 5 years. There was a significant amount of unobserved heterogeneity in the early postoperative period. CONCLUSION: The 5-year post-pancreatectomy empirical survival was 27.5%. Dynamic analyses showed a time-varying structure of prognostic variables and a substantial impact of unobserved tumor characteristics that may drive the disease course under the selective pressure of surgical resection and adjuvant chemotherapy.

Intraoperative Blood Loss Estimation in Hepato-pancreato-biliary Surgery- Relevant, Not Reported, Not Standardized: Results From a Systematic Review and a Worldwide Snapshot Survey.

OBJECTIVE: To provide an overview of the current practice of intraoperative blood loss (BL) estimation in hepato-pancreato-biliary (HPB) surgery. BACKGROUND: Intraoperative BL is a major quality marker in HPB surgery and a predictor of perioperative outcomes. However, the method for BL estimation is not standardized. METHODS: A systematic review was performed of original studies published between 2006 and 2021 reporting the intraoperative BL of patients undergoing pancreatic or hepatic resections. A web-based snapshot survey was distributed globally to all members of the International Hepato-Pancreato-Biliary Association (IHPBA). RESULTS: A total of 806 studies were included; 480 (60%) had BL as their primary outcome, and 105 (13%) had BL as their secondary outcome. However, 669 (83%) did not specify how BL estimation was performed, and 9 different methods were found among the remaining 136 (17%) studies.The survey was completed by 252 surgeons. Most of the responders (94%) declared that they systematically performed BL estimation and considered BL predictive of postoperative complications after pancreatic (73%) and liver (74%) resection. All methods previously identified in the literature were used by responders with different frequencies. A calculation based on suction fluid amounts, operative gauze weight, and irrigation was the most used method in the literature (7%) and among responders (51%). Most responders (83%) felt that BL estimation in HPB surgery needs improved standardization. CONCLUSIONS: Standardization of intraoperative BL estimation is urgently needed in HPB surgery to ensure the consistency of reporting and reproducibility.

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.

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.

Long-Term Follow-Up after Surgery for Chronic Pancreatitis: A Bicentric Retrospective Experience.

INTRODUCTION: The impact of surgery on nutritional status, pancreatic function, and symptoms of patients affected by chronic pancreatitis (CP) has not been unequivocally determined. This study aimed to evaluate clinical follow-up after surgery for CP in an Italian-Austrian population. MATERIALS AND METHODS: Patients operated for CP at two high-volume centers between 2000 and 2018 were analyzed. The following parameters were compared between the pre- and postoperative period: nutritional status, endocrine and exocrine pancreatic functions, and chronic pain. RESULTS: Overall, 186 patients underwent surgery for CP. Among these, 68 (40%) answered a specific follow-up questionnaire. The body mass index showed a significant increase between pre- and postoperative assessments (21.1 vs. 22.5 p = 0.003). Furthermore, a 60% decrease in the prevalence of chronic pain (81 vs. 21%, p < 0.001) was observed. On the contrary, both exocrine and endocrine pancreatic functions pointed toward a worsening after surgery, with consistent higher rates of patients presenting with diabetes mellitus, as well as patients requiring insulin therapy and oral intake of pancreatic enzymes. The analysis of body composition performed on 40 (24%) patients with a complete imaging pack revealed no significant change in the nutritional status after surgery. DISCUSSION/CONCLUSION: Despite the good results observed in terms of pain relief, the surgical approach led to a consistent worsening of the global pancreatic function. No significant influence of surgery on the nutritional status of patients was detected.

Bioethics in an oncological surgery unit during the COVID-19 pandemic: the Verona experience.

The spread of COVID-19 has overwhelmed medical facilities across the globe, with patients filling beds in both regular wards and in intensive care units. The repurposing of hospital facilities has resulted in a dramatic decrease in the capacity of hospitals-in terms of available beds, surgical facilities, and medical and nursing staff- to care for oncology patients. The Italian National Board of Bioethics provided precise and homogeneous guidelines for the allocation of the scarce resources available. In our experience, strictly following these general guidelines and not considering the clinical vocation of each single health care center did not allow us to resume usual activities but generated further confusion in resource allocation. To face the scarcity of available resources and guarantee our patients fair access to the health care system we created a surgical triage with four fundamental steps. We took into consideration " well defined and widely accepted clinical prognostic factors " as stated by the Italian Society of Anesthesia and Resuscitation. We were able to draw up a list of patients giving priority to those who theoretically should have a greater chance of overcoming their critical situation. The age criterion has also been used in the overall evaluation of different cure options in each case, but it has never been considered on its own or outside the other clinical parameters. Although not considered acceptable by many we had to forcefully adopt the criterion of comparison between patients to give priority to those most in need of immediate care.

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.

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.

Pancreatic surgery during COVID-19 pandemic: major activity disruption of a third-level referral center during 2020.

INTRODUCTION: The COVID-19 pandemic has severely limited the access to cancer surgery, but it is not known to what extent referral centers for pancreatic diseases were affected by its outbreak. The aim of this study is to describe the effect of COVID-19 pandemic on a third-level referral center for pancreatic surgery in Italy. METHODS: The 2020 activity of The Pancreas Institute of the University of Verona was reviewed, comparing different phases of the COVID-19 pandemic outbreaks using the pre-COVID era as a control. Endpoints were the overall caseload of pancreatic resections, surgical waiting list, administration of preoperative therapy, major morbidity and mortality, residents' training; number of inpatients beds, outpatient visits/procedures/diagnostics. RESULTS: In 2020, there was an overall significant reduction of pancreatic resections performed (394 vs. 506 in 2019), particularly during the first (March-May) and second (October-December) COVID-19 outbreaks, with an all-time-low of 16 resections/months in April (compared to 43 average resection/month in 2019). The rates of major morbidity (Clavien-Dindo ≥ 3) and mortality were similar to 2019 (16 vs 12%, p = 0.11 and 3 vs 2%, p = 0.29, respectively). During the first and second outbreaks resident's training, inpatient beds, outpatient visits, diagnostics, and procedures were severely impaired, while the waiting list for up-front cancer resections and the use of preoperative chemotherapy concomitantly raised. CONCLUSION: The COVID-19 pandemic has severely disrupted the activity of a third-level referral center for pancreatic surgery, affecting the access to cancer surgical procedures and raising concerns regarding the solidity of the current centralization model.

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.

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.

Surgery for chronic pancreatitis: the comparison of two high-volume centers reveals lack of a uniform operative management.

PURPOSE: Many aspects of surgical therapy for chronic pancreatitis (CP), including the correct indication and timing, as well as the most appropriate operative techniques, are still a matter of debate in the surgical community and vary widely across different centers. The aim of the present study was to uncover and analyze these differences by comparing the experiences of two specialized surgical units in Italy and Austria. METHODS: All patients operated for CP between 2000 and 2018 at the two centers involved were included in this retrospective analysis. Data regarding the clinical history and the pre- and perioperative surgical course were analyzed and compared between the two institutions. RESULTS: Our analysis showed a progressive decrease in the annual rate of pancreatic surgical procedures performed for CP in Verona (no. = 91) over the last two decades (from 3% to less than 1%); by contrast, this percentage increased from 3 to 9% in Vienna (no. = 77) during the same time frame. Considerable differences were also detected with regard to the timing of surgery from the first diagnosis of CP - 4 years (IQR 5.5) in the Austrian series vs two (IQR 4.0) in the Italian series -, and of indications for surgery, with a 12% higher prevalence of groove pancreatitis among patients in the Verona cohort. CONCLUSION: The comparison of the surgical attitude towards CP between two surgical centers proved that a consistent approach to this pathology still is lacking. The identification of common guidelines and labels of surgical eligibility is advisable in order to avoid interinstitutional treatment disparities.

Assessment of difficulty in laparoscopic distal pancreatectomy: A modification of the Japanese difficulty scoring system - A single-center high-volume experience.

BACKGROUND: The Japanese difficulty scoring system (DSS) was developed to assess the difficulty of laparoscopic distal pancreatectomy (LDP). The study aimed to validate a modified DSS (mDSS) in a European high-volume center. METHODS: Patients' clinical data underwent LDP for benign and malignant pancreatic lesion between September 2013 and February 2020 were reviewed. Expert laparoscopic surgeons performed the procedures. The mDSS consisted of seven variables, such as type of operation, malignancy, neoadjuvant therapy, pancreatic resection line, tumor close to major vessels, tumor extension to peripancreatic tissue, and left-sided portal hypertension and/or splenomegaly. According to the difficulty level and previous score, the mDSS was subdivided into three classes: low, intermediate, and high. Surrogates of case complexity (operative time, intraoperative blood loss and blood transfusion requirements, conversion rate) were used to validate the new scoring system. RESULTS: The study population included 140 LDP. Ninety-five (68%), 35 (25%) and 10 (7%) patients belonged to low, intermediate, and high difficulty groups. The mDSS identified the complexity of the surgical case of the series for all the surrogates of complexity considered, namely conversion rate (P = .004), operative time (P = .033) and intraoperative blood loss (P = .009). No differences were recorded in the postoperative outcomes (P > .05). CONCLUSION: The mDSS for LDP better stratified the pancreatic procedures according to their complexity. The new scoring system may allow an appropriate preoperative evaluation of surgical difficulty, facilitating LDP's training program. Future prospective studies are needed to validate the mDSS.

A phase II trial proposal of total neoadjuvant treatment with primary chemotherapy, stereotactic body radiation therapy, and intraoperative radiation therapy in borderline resectable pancreatic adenocarcinoma.

BACKGROUND: The current management guidelines recommend that patients with borderline resectable pancreatic adenocarcinoma (BRPC) should initially receive neoadjuvant chemotherapy. The addition of advanced radiation therapy modalities, including stereotactic body radiation therapy (SBRT) and intraoperative radiation therapy (IORT), could result in a more effective neoadjuvant strategy, with higher rates of margin-free resections and improved survival outcomes. METHODS/DESIGN: In this single-center, single-arm, intention-to-treat, phase II trial newly diagnosed BRPC will receive a "total neoadjuvant" therapy with FOLFIRINOX (5-fluorouracil, irinotecan and oxaliplatin) and hypofractionated SBRT (5 fractions, total dose of 30 Gy with simultaneous integrated boost of 50 Gy on tumor-vessel interface). Following surgical exploration or resection, IORT will be also delivered (10 Gy). The primary endpoint is 3-year survival. Secondary endpoints include completion of neoadjuvant treatment, resection rate, acute and late toxicities, and progression-free survival. In the subset of patients undergoing resection, per-protocol analysis of disease-free and disease-specific survival will be performed. The estimated sample size is 100 patients over a 36-month period. The trial is currently recruiting. TRIAL REGISTRATION: NCT04090463 at clinicaltrials.gov.

Predictors of pancreatic fistula healing time after distal pancreatectomy.

INTRODUCTION: Postoperative pancreatic fistula (POPF) is common after distal pancreatectomy (DP). Whilst extensive investigation into potential predictors has been carried out, there is little evidence regarding POPF healing time. METHODS: This is a retrospective analysis of all consecutive DPs performed at the Department of General and Pancreatic Surgery, University of Verona Hospital Trust, from 2015 to 2019. Perioperative variables were analyzed identifying possible predictors of POPF healing time defined as days between surgery and last drain removal due to POPF. RESULTS: A total of 496 patients were included. POPF rate was 28.2% and median POPF healing time was 30 days (95% CI 28-31). Independent predictors of POPF were body mass index (BMI) (OR 1.073, 95% CI 1.010-1.147, p = 0.040), operative time (OR 95% CI 1.002-1.009, P = .003), and postoperative acute pancreatitis (OR 3.793, 95% CI, 1.852-7.767, P < .001). Independent predictors of POPF healing time were female sex (HR 1.323, 95% CI 1.093-1.998, P = .042), preoperative pancreatic enzyme replacement therapy (HR 2.319, 95% CI 1.195-4.498, P = .013), ASA score 3 (HR 0.278, 95% CI 0.119-0.646, P = .003), pancreatic transection with ultrasonic dissector (HR 0.605, 95% CI 0.404-0.907, P = .015), and positive drain cultures (HR 0.635, 95% CI 0.443-0.910, P = .013). CONCLUSION: POPF healing after DP is a slow process since only half of patients recover within 30 days of surgery. A longer healing time can be predicted early in the postoperative period with significant implications in therapeutic choices.

Redefining the Role of Drain Amylase Value for a Risk-Based Drain Management after Pancreaticoduodenectomy: Early Drain Removal Still Is Beneficial.

BACKGROUND: The application of postoperative pancreatic fistula (POPF) risk stratification and mitigation strategies requires an update of the protocol for an early drain removal after pancreaticoduodenectomy (PD). The aim of the study is to highlight the unreliability of a single drain fluid amylase (DFA) cutoff-based protocol in the setting of a risk-based drain management. METHODS: The role of postoperative day one (POD1) DFA in predicting POPF was explored in the setting of both selective drain placement and early drain removal protocols. Receiver operating characteristics (ROC) curves were used to assess the POPF diagnostic performance in terms of negative predictive value (NPV) of several POD1 DFA cutoffs in different clinical scenarios according to POPF risk and mitigation strategies. RESULTS: The areas under the curve (AUCs) for POD1-DFA were 0.815 for intermediate risk and pancreaticojejunostomy (PJ) (best cutoff 1000 IU/L, NPV 92.9%), 0.712 for intermediate risk and PJ with external stent (best cutoff 1000 IU/L, NPV 88.8%), and 0.574 for high risk and external stent (best cutoff 250 IU/L, NPV 93.7%). Independent predictors of POPF were body mass index, pancreatic texture, and early drain removal, whereas POD1 DFA was not. CONCLUSION: In the era of risk stratification and mitigation strategies, selective early drain removal still is associated with a reduced rate of POPF. However, a single protocol based on POD1-DFA is not suitable for all clinical scenarios after PD.

Pancreatic surgery is a safe teaching model for tutoring residents in the setting of a high-volume academic hospital: a retrospective analysis of surgical and pathological outcomes.

BACKGROUND: Academic hospitals must train future surgeons, but whether residents could negatively affect the outcomes of major procedures is a matter of concern. The aim of this study is to assess if pancreatic surgery is a safe teaching model. METHODS: Outcomes of 1230 major pancreatic resections performed at a high-volume pancreatic teaching hospital between 2015 and 2018 were compared according to the first surgeon type, attending vs resident. RESULTS: Residents performed a selection of 132 (16%) pancreaticoduodenectomies (PD) and 46 (11%) distal pancreatectomies (DP). For PD, pancreatic fistula (25% vs 0, p < 0.001), biliary fistula (7.1% vs 3.5%, p = 0.04) and operative time (400 vs 390 min, p < 0.001) were lower for residents but post-pancreatectomy hemorrhage was higher (20.5% vs 13% p = 0.024). For DP, pancreatic fistula rate was lower for residents (31.7% vs 17.5% p = 0.046). There was no difference in terms of lymph nodes retrieval both for PDs and DPs, while the R1 resections were more frequent among PDs performed by attending surgeons (31.5% vs 15.7%, p = 0.023). CONCLUSION: The active participation of residents does not negatively affect outcomes of major pancreatic resections in a high-volume center. By means of case selection and continuous tutoring, pancreatic surgery represents a safe and valid teaching model.

Cost-effectiveness and quality of life analysis of laparoscopic and robotic distal pancreatectomy: a propensity score-matched study.

BACKGROUND: This study analyzed the Quality of Life (QoL) and cost-effectiveness of laparoscopic (LDP) versus robotic distal pancreatectomy (RDP). METHOD: All patients who underwent LDP or RDP from 2011 to 2017 and with a minimum postoperative follow-up of 12 months were included in the study. To minimize bias, a propensity score-matched analysis (1:2) was performed. Two different questionnaires (EORTC QLQ-C30 and EQ-5D) were completed by the patients. The mean differential cost and mean differential Quality Adjusted Life Years (QALY) were calculated and plotted on a cost-utility plane. RESULTS: The study population consisted of 152 patients. After having applied the propensity score matching, the final population included 103 patients divided into RDP group (n = 37, 36%) and LDP (n = 66, 64%). No differences were found between groups regarding the baseline, intraoperative, postoperative, and pathological variables (p > 0.05). The QoL analysis showed a significant improvement in the RDP group on the postoperative social function, nausea, vomiting, and financial status (p = 0.010, p = 0.050, and p = 0.030, respectively). As expected, the crude costs analysis confirmed that RDP was more expensive than LDP (12,053 Euros vs. 5519 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 of more than 4800 Euros/QALY was accepted. CONCLUSION: RDP was associated with QoL improvement in specific domains. Crude costs were higher relative to LDP. Cost-effectiveness threshold resulted to be 4800 euros/QALY. The increasing worldwide diffusion of the robotic technology, with easier access and possible cost reduction, could increase the sustainability of this procedure.