Postoperative Hyperamylasemia (POH) is an Early Predictor of Pancreatic Fistula Occurrence and Severity after Distal Pancreatectomy: Results from a European Multicentric Study.

OBJECTIVES: The aim of this international multicentric study is to characterize postoperative hyperamylasemia (POH) after distal pancreatectomy (DP), with particular focus on its relationship with postoperative pancreatic fistula (POPF) occurrence and severity. BACKGROUND: The clinical relevance of POH after DP and its relationship with the occurrence and severity of POPF have not been explored yet. METHODS: All patients undergoing DP for any indication between 2015 and 2021 at three European referral Centers for pancreatic surgery were retrospectively analyzed. Drain fluid amylase (DFA), C-reactive protein (C-RP), and serum amylase were examined from postoperative-day (POD) 1 to 3. Biochemical leak (BL), POPF, POH, and post-pancreatectomy hemorrhage (PPH) were defined and graded according to ISGPS definitions. RESULTS: In total 1192 patients were included. Overall rates of POH and POPF were 18% (n= 210) and 29% (n= 344), respectively. The presence of DFA ≥2000 U/L on POD 1 (OR=2.11, 95% CI 1.68-2.86), C-RP ≥200 mg/L on POD 3 (OR=2.19, 95% CI 1.68-2.86), and POH (OR=1.58, 95% CI 1.14-2.19) were all independent early predictors of POPF (all P< 0.01). The presence of POH almost doubled the rate of POPF (43% vs. 26%, P<0.001), and higher POPF severity presented also higher POH rates (no POPF= 12%; BL= 19%; B POPF= 24%; C POPF= 52%). Among patients developing POPF, patients with POH had higher rates of PPH (22% vs 9%, P= 0.001), sepsis (24% vs 13%; P=0.011), re-operation (21% vs 8%; P< 0.01), and mortality (3% vs 0.3%; P= 0.025). CONCLUSIONS: The occurrence of POH is an early predictor of POPF and its severity after DP. The diagnosis of POH might define patients at higher risk for a complicated course, targeting them for prevention / mitigation strategies against pancreas specific complications.

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.

Robotic hepaticojejunostomy training in novices using robotic simulation and dry-lab suturing (ROSIM): randomized controlled crossover trial.

BACKGROUND: Robotic suturing training is in increasing demand and can be done using suture-pads or robotic simulation training. Robotic simulation is less cumbersome, whereas a robotic suture-pad approach could be more effective but is more costly. A training curriculum with crossover between both approaches may be a practical solution. However, studies assessing the impact of starting with robotic simulation or suture-pads in robotic suturing training are lacking. METHODS: This was a randomized controlled crossover trial conducted with 20 robotic novices from 3 countries who underwent robotic suturing training using an Intuitive Surgical® X and Xi system with the SimNow (robotic simulation) and suture-pads (dry-lab). Participants were randomized to start with robotic simulation (intervention group, n = 10) or suture-pads (control group, n = 10). After the first and second training, all participants completed a robotic hepaticojejunostomy (HJ) in biotissue. Primary endpoint was the objective structured assessment of technical skill (OSATS) score during HJ, scored by two blinded raters. Secondary endpoints were force measurements and a qualitative analysis. After training, participants were surveyed regarding their preferences. RESULTS: Overall, 20 robotic novices completed both training sessions and performed 40 robotic HJs. After both trainings, OSATS was scored higher in the robotic simulation-first group (3.3 ± 0.9 vs 2.5 ± 0.8; p = 0.049), whereas the median maximum force (N) (5.0 [3.2-8.0] vs 3.8 [2.3-12.8]; p = 0.739) did not differ significantly between the groups. In the survey, 17/20 (85%) participants recommended to include robotic simulation training, 14/20 (70%) participants preferred to start with robotic simulation, and 20/20 (100%) to include suture-pad training. CONCLUSION: Surgical performance during robotic HJ in robotic novices was significantly better after robotic simulation-first training followed by suture-pad training. A robotic suturing curriculum including both robotic simulation and dry-lab suturing should ideally start with robotic simulation.

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.

Preoperative predictive factors of laparoscopic distal pancreatectomy difficulty.

BACKGROUND: Laparoscopic distal pancreatectomy (LDP) is a challenging operation due to technical complexity and tumor-related factors. Aim of this study was to identify preoperative risk factors affecting LDP difficulty. METHODS: Consecutive patients who underwent LDP between 2015 and 2018 at San Raffaele Hospital and Policlinico S.Orsola-Malpighi Hospital were enrolled retrospectively. Three variables were used to define surgical difficulty: conversion to open, duration of surgery >3rd quartile and intraoperative blood loss >3rd quartile. The presence of ≥1 of these 3 variables was considered as another measure of difficulty. RESULTS: Overall, 191 patients were included. Conversion to open was required in 25 patients (13%). At multiple regression analysis, tumor proximity to major vessels was the only independent predictor of conversion from laparoscopic to open (p < 0.001). No variables independently predicted an excessive duration of surgery. Male gender (p = 0.033) and increasing parenchymal thickness at resection line (p = 0.018) were independent predictors of excessive blood loss. Increasing parenchymal thickness at resection line (p = 0.014) and tumor proximity to major vessels (p = 0.002) were significant risk factors for the presence of ≥1 outcome of surgical difficulty. CONCLUSION: Male gender, increasing parenchymal thickness at resection line and tumor proximity to major vessels represent preoperative risk factors of LDP difficulty.

REDISCOVER guidelines for borderline-resectable and locally advanced pancreatic cancer: management algorithm, unanswered questions, and future perspectives.

The REDISCOVER guidelines present 34 recommendations for the selection and perioperative care of borderline-resectable (BR-PDAC) and locally advanced ductal adenocarcinoma of the pancreas (LA-PDAC). These guidelines represent a significant shift from previous approaches, prioritizing tumor biology over anatomical features as the primary indication for resection. Condensed herein, they provide a practical management algorithm for clinical practice. However, the guidelines also highlight the need to redefine LA-PDAC to align with modern treatment strategies and to solve some contradictions within the current definition, such as grouping "difficult" and "impossible" to resect tumors together. Furthermore, the REDISCOVER guidelines highlight several areas requiring urgent research. These include the resection of the superior mesenteric artery, the management strategies for patients with LA-PDAC who are fit for surgery but unable to receive multi-agent neoadjuvant chemotherapy, the approach to patients with LA-PDAC who are fit for surgery but demonstrate high serum Ca 19.9 levels even after neoadjuvant treatment, and the optimal timing and number of chemotherapy cycles prior to surgery. Additionally, the role of primary chemoradiotherapy versus chemotherapy alone in LA-PDAC, the timing of surgical resection post-neoadjuvant/primary chemoradiotherapy, the efficacy of ablation therapies, and the management of oligometastasis in patients with LA-PDAC warrant investigation. Given the limited evidence for many issues, refining existing management strategies is imperative. The establishment of the REDISCOVER registry ( https://rediscover.unipi.it/ ) offers promise of a unified research platform to advance understanding and improve the management of BR-PDAC and LA-PDAC.

Treatment strategies to prevent or mitigate the outcome of post-pancreatectomy hemorrhage (PPH): a review of randomized trials.

BACKGROUND: Post-pancreatectomy hemorrhage (PPH) is a leading cause for surgical mortality after pancreatic surgery. Several strategies for the prevention and management of PPH have been studied in randomized controlled trials (RCTs) but a systematic review is lacking. We systematically reviewed RCTs regarding the impact of treatment strategies on the incidence and outcome of PPH. MATERIAL AND METHODS: Eligible RCTs reporting on impact of treatment on the rate of PPH were identified through a systematic literature search using the Evidence Map of Pancreatic Surgery (2012-2022). Methodological quality was assessed using the Cochrane Risk of Bias 2 (RoB-2) tool for RCTs. Various definitions of PPH were accepted and outcome reported separately for the International Study Group for Pancreatic Surgery (ISGPS) definition. RESULTS: Overall, 99 RCTs fulfilled the eligibility criteria with a pooled 6.1% rate of PPH (range 1%-32%). The pooled rate of PPH defined as ISGPS grade B/C was 8.1% (range 0-24.9%). Five RCTs reported five strategies that significantly reduced the rate of PPH. Three concerned surgical technique: pancreatic anastomosis with small jejunal incision, falciform ligament wrap around the gastroduodenal artery stump, and pancreaticojejunostomy (vs pancreaticogastrostomy). Two concerned perioperative management: perioperative pasireotide administration, and algorithm-based postoperative patient management. No single RCT specifically focused on the treatment of patients with PPH. CONCLUSION: This systematic review of RCTs identified five strategies which reduce the rate of PPH; three concerning intraoperative surgical technique and two concerning peri-operative patient management. Future studies should focus on the treatment of patients with PPH as RCTs are currently lacking.

Robotic D3 Partial Duodenal Resection with Primary Side-to-Side Anastomosis.

Duodenal stenosis is a condition that can be related to several diseases, being either intrinsic, such as neoplasm and inflammatory stenosis, or extrinsic, such as pancreatic pseudocyst, superior mesenteric artery syndrome, and foreign bodies. Current treatments range from endoscopic approaches, such as endoscopic resection and stent placement, to surgical approaches, including duodenal resection, pancreaticoduodenectomy, and gastrointestinal bypass. Minimally invasive robot-assisted surgery is gaining importance due to its potential to decrease surgical stress, intraoperative blood loss, and postoperative pain, while its instruments and 3D-vision facilitate fine dissection and intra-abdominal suturing, all leading to a reduced time to functional recovery and shorter hospital stay. We present a case of a 75-year-old female who underwent robotic D3 partial duodenal resection with primary side-to-side duodeno-jejunal anastomosis for a 5 cm adenoma with focal high-grade dysplasia.

Evaluation of cost-effectiveness among open, laparoscopic and robotic distal pancreatectomy: A systematic review and meta-analysis.

BACKGROUND: The cost-effectiveness of minimally invasive distal pancreatectomy (MIDP) is still a matter of debate. This study compares the cost-effectiveness of open (ODP), laparoscopic (LDP) and robotic distal pancreatectomy (RDP). METHODS: Pubmed, Web of Science and Cochrane Library databases were searched. Studies comparing cost-effectiveness of ODP and MIDP were included. RESULTS: A total of 1052 titles were screened and 16 articles were included in the study, 2431 patients in total. LDP resulted the most cost-efficient procedure, with a mean total cost of 14,682 ± 5665 € and the lowest readmission rates. ODP had lower surgical procedure costs, 3867 ± 768 €. RDP was the safest approach regarding hospital stay costs (5239 ± 1741 €), length of hospital stay, morbidity, clinically relevant pancreatic fistula and reoperations. CONCLUSION: In this meta-analysis MIDP resulted as the most cost-effective approach. LDP seems to be protective against high costs, but RDP seems to be safer.