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.

Reappraising the Role of Intraoperative Neck Margin Revision in Post-Neoadjuvant Pancreatoduodenectomy for Pancreatic Ductal Adenocarcinoma: A Multi-Institutional Analysis.

OBJECTIVE: To investigate whether revision of pancreatic neck margin based on intraoperative frozen section analysis has oncologic value in post-neoadjuvant pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). SUMMARY BACKGROUND DATA: The role of intraoperative neck margin revision has been controversial, with little information specific to post-neoadjuvant PD. METHODS: Patients who underwent post-neoadjuvant PD (2013-2019) for conventional PDAC with frozen section analysis of neck margin at three academic institutions were included. Overall survival (OS) and recurrence-free survival (RFS) were compared across three groups: complete resection achieved en-bloc (CR-EB), complete resection achieved non-en-bloc (CR-NEB), and incomplete resection (IR). RESULTS: Among the 671 patients included, 524 (78.1%) underwent CR-EB, 119 (17.7%) CR-NEB and 28 (4.2%) IR. Patients undergoing CR-NEB and IR exhibited larger tumors and lower rates of RECIST response, requiring vascular resections more often. Likewise, CR-NEB and IR were associated with a worse pathological profile than CR-EB. The incidence of postoperative complications and access to adjuvant treatment were comparable among groups. A CR-EB was associated with the longest OS duration (34.3 mo). In patients with positive neck margin, obtaining a CR-NEB via re-excision was associated with a comparable OS relative to patients with an IR (26.9 vs. 27.1 mo, P=0.901). Similar results were observed for RFS. At multivariable analysis, neck margin status was not independently associated with survival and recurrence. CONCLUSION: Conversion of an initially positive pancreatic neck margin by additional resection is not associated with oncologic benefits in post-neoadjuvant PD and cannot be routinely recommended.

The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS).

OBJECTIVE: To develop and update evidence-based and consensus-based guidelines on laparoscopic and robotic pancreatic surgery. SUMMARY BACKGROUND DATA: Minimally invasive pancreatic surgery (MIPS), including laparoscopic and robotic surgery, is complex and technically demanding. Minimizing the risk for patients requires stringent, evidence-based guidelines. Since the International Miami Guidelines on MIPS in 2019, new developments and key publications have been reported, necessitating an update. METHODS: Evidence-based guidelines on 22 topics in 8 domains were proposed: terminology, indications, patients, procedures, surgical techniques and instrumentation, assessment tools, implementation and training, and artificial intelligence. The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS, September 2022) used the Scottish Intercollegiate Guidelines Network (SIGN) methodology to assess the evidence and develop guideline recommendations, the Delphi method to establish consensus on the recommendations among the Expert Committee, and the AGREE II-GRS tool for guideline quality assessment and external validation by a Validation Committee. RESULTS: Overall, 27 European experts, 6 international experts, 22 international Validation Committee members, 11 Jury Committee members, 18 Research Committee members, and 121 registered attendees of the 2-day meeting were involved in the development and validation of the guidelines. In total, 98 recommendations were developed, including 33 on laparoscopic, 34 on robotic, and 31 on general MIPS, covering 22 topics in 8 domains. Out of 98 recommendations, 97 reached at least 80% consensus among the experts and congress attendees, and all recommendations were externally validated by the Validation Committee. CONCLUSIONS: The EGUMIPS evidence-based guidelines on laparoscopic and robotic MIPS can be applied in current clinical practice to provide guidance to patients, surgeons, policy-makers, and medical societies.

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.

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.

Combined SERS-Raman screening of HER2-overexpressing or silenced breast cancer cell lines.

BACKGROUND: Breast cancer (BC) is a heterogeneous neoplasm characterized by several subtypes. One of the most aggressive with high metastasis rates presents overexpression of the human epidermal growth factor receptor 2 (HER2). A quantitative evaluation of HER2 levels is essential for a correct diagnosis, selection of the most appropriate therapeutic strategy and monitoring the response to therapy. RESULTS: In this paper, we propose the synergistic use of SERS and Raman technologies for the identification of HER2 expressing cells and its accurate assessment. To this end, we selected SKBR3 and MDA-MB-468 breast cancer cell lines, which have the highest and lowest HER2 expression, respectively, and MCF10A, a non-tumorigenic cell line from normal breast epithelium for comparison. The combined approach provides a quantitative estimate of HER2 expression and visualization of its distribution on the membrane at single cell level, clearly identifying cancer cells. Moreover, it provides a more comprehensive picture of the investigated cells disclosing a metabolic signature represented by an elevated content of proteins and aromatic amino acids. We further support these data by silencing the HER2 gene in SKBR3 cells, using the RNA interference technology, generating stable clones further analysed with the same combined methodology. Significant changes in HER2 expression are detected at single cell level before and after HER2 silencing and the HER2 status correlates with variations of fatty acids and downstream signalling molecule contents in the context of the general metabolic rewiring occurring in cancer cells. Specifically, HER2 silencing does reduce the growth ability but not the lipid metabolism that, instead, increases, suggesting that higher fatty acids biosynthesis and metabolism can occur independently of the proliferating potential tied to HER2 overexpression. CONCLUSIONS: Our results clearly demonstrate the efficacy of the combined SERS and Raman approach to definitely pose a correct diagnosis, further supported by the data obtained by the HER2 gene silencing. Furthermore, they pave the way to a new approach to monitor the efficacy of pharmacologic treatments with the aim to tailor personalized therapies and optimize patients' outcome.

TGS1 impacts snRNA 3'-end processing, ameliorates survival motor neuron-dependent neurological phenotypes in vivo and prevents neurodegeneration.

Trimethylguanosine synthase 1 (TGS1) is a highly conserved enzyme that converts the 5'-monomethylguanosine cap of small nuclear RNAs (snRNAs) to a trimethylguanosine cap. Here, we show that loss of TGS1 in Caenorhabditis elegans, Drosophila melanogaster and Danio rerio results in neurological phenotypes similar to those caused by survival motor neuron (SMN) deficiency. Importantly, expression of human TGS1 ameliorates the SMN-dependent neurological phenotypes in both flies and worms, revealing that TGS1 can partly counteract the effects of SMN deficiency. TGS1 loss in HeLa cells leads to the accumulation of immature U2 and U4atac snRNAs with long 3' tails that are often uridylated. snRNAs with defective 3' terminations also accumulate in Drosophila Tgs1 mutants. Consistent with defective snRNA maturation, TGS1 and SMN mutant cells also exhibit partially overlapping transcriptome alterations that include aberrantly spliced and readthrough transcripts. Together, these results identify a neuroprotective function for TGS1 and reinforce the view that defective snRNA maturation affects neuronal viability and function.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Importance of Nodal Metastases Location in Pancreatoduodenectomy for Pancreatic Ductal Adenocarcinoma: Results from a Prospective, Lymphadenectomy Protocol.

BACKGROUND: Implementing a prospective lymphadenectomy protocol, we investigated the nodal yields and metastases per anatomical stations and nodal echelon following upfront pancreatoduodenectomy (PD) for cancer. Next, the relationship between the extension of nodal dissection, the number of examined and positive nodes (ELN/PLN), disease staging and prognosis was assessed. METHODS: Lymphadenectomy included stations 5, 6, 8a-p, 12a-b-p, 13, 14a-b, 17, and jejunal mesentery nodes. Data were stratified by N-status, anatomical stations, and nodal echelons. First echelon was defined as stations embedded in the main specimen and second echelon as stations sampled as separate specimens. Recurrence and survival analyses were performed by using standard statistics. RESULTS: Overall, 424 patients were enrolled from June 2013 through December 2018. The median number of ELN and PLN was 42 (interquartile range [IQR] 34-50) and 4 (IQR 2-8). Node-positive patients were 88.2%. The commonest metastatic sites were stations 13 (77.8%) and 14 (57.5%). The median number of ELN and PLN in the first echelon was 28 (IQR 23-34) and 4 (IQR 1-7). While first-echelon dissection provided enough ELN for optimal nodal staging, the aggregate rate of second-echelon metastases approached 30%. Nodal-related factors associated with recurrence and survival were N-status, multiple metastatic stations, metastases to station 14, and jejunal mesentery nodes. CONCLUSIONS: First-echelon dissection provides adequate number of ELN for optimal staging. Nodal metastases occur mostly at stations 13/14, although second-echelon involvement is frequent. Only station 14 and jejunal mesentery nodes involvement was prognostically relevant. This latter station should be included in the standard nodal map and analyzed pathologically.

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.