ATP6V1A is required for synaptic rearrangements and plasticity in murine hippocampal neurons.

AIM: Understanding the physiological role of ATP6V1A, a component of the cytosolic V1 domain of the proton pump vacuolar ATPase, in regulating neuronal development and function. METHODS: Modeling loss of function of Atp6v1a in primary murine hippocampal neurons and studying neuronal morphology and function by immunoimaging, electrophysiological recordings and electron microscopy. RESULTS: Atp6v1a depletion affects neurite elongation, stabilization, and function of excitatory synapses and prevents synaptic rearrangement upon induction of plasticity. These phenotypes are due to an overall decreased expression of the V1 subunits, that leads to impairment of lysosomal pH-regulation and autophagy progression with accumulation of aberrant lysosomes at neuronal soma and of enlarged vacuoles at synaptic boutons. CONCLUSIONS: These data suggest a physiological role of ATP6V1A in the surveillance of synaptic integrity and plasticity and highlight the pathophysiological significance of ATP6V1A loss in the alteration of synaptic function that is associated with neurodevelopmental and neurodegenerative diseases. The data further support the pivotal involvement of lysosomal function and autophagy flux in maintaining proper synaptic connectivity and adaptive neuronal properties.

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.

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.

Process and quality evaluation of different improved composts made with a smart laboratory pilot plant.

This study monitored the process and investigated the quality of compost obtained from different biomasses. Five blends of agri-food waste were composted by a laboratory pilot plant named COMPOSTER, that is designed to optimize biodegradation, and produce compost efficiently. The COMPOSTER consists of two 35-liter nearly adiabatic, aerated bioreactors that simulate an industrial process involving the typical sequence of mesophilic-thermophilic-mesophilic phases. It continuously monitors and records temperature, internal pressure, and biomass weight, while controlling and quantifying oxygen consumption and carbon dioxide emissions resulting from aerobic biodegradation. All composts were characterized for their main chemical, physical, and molecular features, as well as their suppressiveness against Fusarium oxysporum f.sp. lycopersici (FOL), tested on tomato seedlings. Optimized biodegradation yielded 50-60 % mature compost with a cumulative oxygen consumption ranging from 282 to 456 gO2 per kg of dry matter, with peaks of 2.55 gO2 per kg of volatile solids per hour, and carbon dioxide emissions of 22-36 % of the initial carbon content, with peaks of 5.89 g CO2 per kg of volatile solids per hour. Blends containing more ligno-cellulosic ingredients showed higher yields and lower CO2 emissions. Most of the nitrogen present initially was retained in the final compost; indeed, all mixtures exhibited an apparent nitrogen concentration increase due to carbon loss. Composting determined deep modifications in the molecular structure of the organic matter. 13C CPMAS-NMR and off-line thermochemolysis GC-MS analyses highlighted decomposition degree of polysaccharides and peptidic moieties, selective preservation of aliphatic and aromatic recalcitrant compounds, and optimal ongoing humification. All composts were non-phytotoxic, except for that including pepper crop residues, and all resulted rich in macro- and micro-elements for plant nutrition and proved to be active in controlling FOL disease. Compost comprising 81.2 % tomato crop waste exhibited the best growth performance and pathogen control on tomato. Mature, non-phytotoxic, nutrient-rich, and suppressive composts represent promising by-products that can be successfully recycled in agriculture, including high-value applications, leading to lower use of fertilizers and pesticides.

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.

The pan - COVID - AGICT study. The impact of COVID-19 pandemic on surgically treated pancreatic cancer patients. A multicentric Italian study.

BACKGROUND: In this article we aimed to perform a subgroup analysis using data from the COVID-AGICT study, to investigate the perioperative outcomes of patients undergoing surgery for pancreatic cancers (PC) during the COVID-19 pandemic. METHODS: The primary endpoint of the study was to find out any difference in the tumoral stage of surgically treated PC patients between 2019 and 2020. Surgical and oncological outcomes of the entire cohort of patients were also appraised dividing the entire peri-pandemic period into six three-month timeframes to balance out the comparison between 2019 and 2020. RESULTS: Overall, a total of 1815 patients were surgically treated during 2019 and 2020 in 14 Italian surgical Units. In 2020, the rate of patients treated with an advanced pathological stage was not different compared to 2019 (p = 0.846). During the pandemic, neoadjuvant chemotherapy (NCT) has dropped significantly (6.2% vs 21.4%, p < 0.001) and, for patients who didn't undergo NCT, the latency between diagnosis and surgery was shortened (49.58 ± 37 days vs 77.40 ± 83 days, p < 0.001). During 2020 there was a significant increase in minimally invasive procedures (p < 0.001). The rate of postoperative complication was the same in the two years but during 2020 there was an increase of the medical ones (19% vs 16.1%, p = 0.001). CONCLUSIONS: The post-pandemic dramatic modifications in healthcare provision, in Italy, did not significantly impair the clinical history of PC patients receiving surgical resection. The present study is one of the largest reports available on the argument and may provide the basis for long-term analyses.

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.

Intraperitoneal prophylactic drain after pancreaticoduodenectomy: an Italian survey.

Intraperitoneal prophylactic drain (IPD) use in pancreaticoduodenectomy (PD) is still controversial. A survey was designed to investigate surgeons' use of IPD in PD patients through 23 questions and one clinical vignette. For the clinical scenario, respondents were asked to report their regret of omission and commission regarding the use of IPD elicited on a scale between 0 (no regret) and 100 (maximum regret). The threshold model and a multilevel mixed regression were applied. One hundred three (97.2%) respondents confirmed using at least two IPDs. The median regret due to the omission of IPD was 84 (67-100, IQR). The median regret due to the commission of IPD was 10 (3.5-20, IQR). The CR-POPF probability threshold at which drainage omission was the less regrettable choice was 3% (1-50, IQR). The threshold was lower for those surgeons who performed minimally invasive PD (P = 0.048), adopted late removal (P = 0.002), perceived FRS able to predict the risk (P = 0.006), and IPD able to avoid relaparotomy P = 0.036). Drain management policies after PD remain heterogeneous among surgeons. The regret model suggested that IPD omission could be performed in low-risk patients.

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.

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.

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.

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.

Prospective minimally invasive pancreatic resections from the IGOMIPS registry: a snapshot of daily practice in Italy on 1191 between 2019 and 2022.

This retrospective analysis of the prospective IGOMIPS registry reports on 1191 minimally invasive pancreatic resections (MIPR) performed in Italy between 2019 and 2022, including 668 distal pancreatectomies (DP) (55.7%), 435 pancreatoduodenectomies (PD) (36.3%), 44 total pancreatectomies (3.7%), 36 tumor enucleations (3.0%), and 8 central pancreatectomies (0.7%). Spleen-preserving DP was performed in 109 patients (16.3%). Overall incidence of severe complications (Clavien-Dindo ≥ 3) was 17.6% with a 90-day mortality of 1.9%. This registry analysis provided some important information. First, robotic assistance was preferred for all MIPR but DP with splenectomy. Second, robotic assistance reduced conversion to open surgery and blood loss in comparison to laparoscopy. Robotic PD was also associated with lower incidence of severe postoperative complications and a trend toward lower mortality. Fourth, the annual cut-off of ≥ 20 MIPR and ≥ 20 MIPD improved selected outcome measures. Fifth, most MIPR were performed by a single surgeon. Sixth, only two-thirds of the centers performed spleen-preserving DP. Seventh, DP with splenectomy was associated with higher conversion rate when compared to spleen-preserving DP. Eighth, the use of pancreatojejunostomy was the prevalent reconstruction in PD. Ninth, final histology was similar for MIPR performed at high- and low-volume centers, but neoadjuvant chemotherapy was used more frequently at high-volume centers. Finally, this registry analysis raises important concerns about the reliability of R1 assessment underscoring the importance of standardized pathology of pancreatic specimens. In conclusion, MIPR can be safely implemented on a national scale. Further analyses are required to understand nuances of implementation of MIPR in Italy.

Minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer (DIPLOMA): an international randomised non-inferiority trial.

Background: The oncological safety of minimally invasive surgery has been questioned for several abdominal cancers. Concerns also exist regarding the use of minimally invasive distal pancreatectomy (MIDP) in patients with resectable pancreatic cancer as randomised trials are lacking. Methods: In this international randomised non-inferiority trial, we recruited adults with resectable pancreatic cancer from 35 centres in 12 countries. Patients were randomly assigned to either MIDP (laparoscopic or robotic) or open distal pancreatectomy (ODP). Both patients and pathologists were blinded to the assigned approach. Primary endpoint was radical resection (R0, ≥1 mm free margin) in patients who had ultimately undergone resection. Analyses for the primary endpoint were by modified intention-to-treat, excluding patients with missing data on primary endpoint. The pre-defined non-inferiority margin of -7% was compared with the lower limit of the two-sided 90% confidence interval (CI) of absolute difference in the primary endpoint. This trial is registered with the ISRCTN registry (ISRCTN44897265). Findings: Between May 8, 2018 and May 7, 2021, 258 patients were randomly assigned to MIDP (131 patients) or ODP (127 patients). Modified intention-to-treat analysis included 114 patients in the MIDP group and 110 patients in the ODP group. An R0 resection occurred in 83 (73%) patients in the MIDP group and in 76 (69%) patients in the ODP group (difference 3.7%, 90% CI -6.2 to 13.6%; pnon-inferiority = 0.039). Median lymph node yield was comparable (22.0 [16.0-30.0] vs 23.0 [14.0-32.0] nodes, p = 0.86), as was the rate of intraperitoneal recurrence (41% vs 38%, p = 0.45). Median follow-up was 23.5 (interquartile range 17.0-30.0) months. Other postoperative outcomes were comparable, including median time to functional recovery (5 [95% CI 4.5-5.5] vs 5 [95% CI 4.7-5.3] days; p = 0.22) and overall survival (HR 0.99, 95% CI 0.67-1.46, p = 0.94). Serious adverse events were reported in 23 (18%) of 131 patients in the MIDP group vs 28 (22%) of 127 patients in the ODP group. Interpretation: This trial provides evidence on the non-inferiority of MIDP compared to ODP regarding radical resection rates in patients with resectable pancreatic cancer. The present findings support the applicability of minimally invasive surgery in patients with resectable left-sided pancreatic cancer. Funding: Medtronic Covidien AG, Johnson & Johnson Medical Limited, Dutch Gastroenterology Society.

Learning Curves of Minimally Invasive Distal Pancreatectomy in Experienced Pancreatic Centers.

Importance: Understanding the learning curve of a new complex surgical technique helps to reduce potential patient harm. Current series on the learning curve of minimally invasive distal pancreatectomy (MIDP) are mostly small, single-center series, thus providing limited data. Objective: To evaluate the length of pooled learning curves of MIDP in experienced centers. Design, Setting, and Participants: This international, multicenter, retrospective cohort study included MIDP procedures performed from January 1, 2006, through June 30, 2019, in 26 European centers from 8 countries that each performed more than 15 distal pancreatectomies annually, with an overall experience exceeding 50 MIDP procedures. Consecutive patients who underwent elective laparoscopic or robotic distal pancreatectomy for all indications were included. Data were analyzed between September 1, 2021, and May 1, 2022. Exposures: The learning curve for MIDP was estimated by pooling data from all centers. Main Outcomes and Measures: The learning curve was assessed for the primary textbook outcome (TBO), which is a composite measure that reflects optimal outcome, and for surgical mastery. Generalized additive models and a 2-piece linear model with a break point were used to estimate the learning curve length of MIDP. Case mix-expected probabilities were plotted and compared with observed outcomes to assess the association of changing case mix with outcomes. The learning curve also was assessed for the secondary outcomes of operation time, intraoperative blood loss, conversion to open rate, and postoperative pancreatic fistula grade B/C. Results: From a total of 2610 MIDP procedures, the learning curve analysis was conducted on 2041 procedures (mean [SD] patient age, 58 [15.3] years; among 2040 with reported sex, 1249 were female [61.2%] and 791 male [38.8%]). The 2-piece model showed an increase and eventually a break point for TBO at 85 procedures (95% CI, 13-157 procedures), with a plateau TBO rate at 70%. The learning-associated loss of TBO rate was estimated at 3.3%. For conversion, a break point was estimated at 40 procedures (95% CI, 11-68 procedures); for operation time, at 56 procedures (95% CI, 35-77 procedures); and for intraoperative blood loss, at 71 procedures (95% CI, 28-114 procedures). For postoperative pancreatic fistula, no break point could be estimated. Conclusion and Relevance: In experienced international centers, the learning curve length of MIDP for TBO was considerable with 85 procedures. These findings suggest that although learning curves for conversion, operation time, and intraoperative blood loss are completed earlier, extensive experience may be needed to master the learning curve of MIDP.

The MIS-COVID-AGICT Study: Trend of Minimally Invasive Surgery for Gastrointestinal Cancer Treatment During the First Waves of the COVID-19 Pandemic in Italy. Subgroup Analysis from the COVID-AGICT Study: COVID-19 and Advanced Gastrointestinal Cancer Surgical Treatment.

Background: A preliminary analysis from the COVID-Advanced Gastrointestinal Cancer Surgical Treatment (AGICT) study showed that the rate of minimally invasive surgery (MIS) for elective and urgent procedures did not decrease during the pandemic year. In this article, we aimed to perform a subgroup analysis using data from the COVID-AGICT study to evaluate the trend of MIS during the COVID-19 pandemic period in Italy. Methods: This study was conducted collecting data of MIS patients from the COVID-AGICT database. The primary endpoint was to demonstrate whether the SARS-CoV-2 pandemic scenario reduced MIS for elective treatment of gastrointestinal cancer (GIC) in Italy in 2020. The secondary endpoint was to evaluate the impact of the pandemic period on perioperative outcomes in the MIS group. Results: In the pandemic year, 62% of patients underwent surgery with a minimally invasive approach, compared to 63% in 2019 (P = .23). In 2020, the proportion of patients undergoing elective MIS decreased compared to the previous year (80% versus 82%, P = .04), and the rate of urgent MIS did not differ between the 2 years (31% and 33% in 2019 and 2020 - P = .66). Colorectal cancer was less likely to be treated with MIS approach during 2020 (78% versus 75%, P < .001). Conversely, the rate of MIS pancreatic resection was higher in 2020 (28% versus 22%, P < .002). Conversion to an open approach was lower in 2020 (7.2% versus 9.2% - P = .01). Major postoperative complications were similar in both years (11% versus 11%, P = .9). Conclusion: In conclusion, although MIS for elective treatment of GIC in Italy was reduced during the COVID-19 pandemic period, our study revealed that the overall proportion of MIS (elective and urgent) and postoperative outcomes were comparable to the prepandemic period. ClinicalTrial.gov (NCT04686747).

The COVID - AGICT study: COVID-19 and advanced gastro-intestinal cancer surgical treatment. A multicentric Italian study on the SARS-CoV-2 pandemic impact on gastro-intestinal cancers surgical treatment during the 2020. Analysis of perioperative and short-term oncological outcomes.

BACKGROUND: This Italian multicentric retrospective study aimed to investigate the possible changes in outcomes of patients undergoing surgery for gastrointestinal cancers during the COVID-19 pandemic. METHOD: Our primary endpoint was to determine whether the pandemic scenario increased the rate of patients with colorectal, gastroesophageal, and pancreatic cancers resected at an advanced stage in 2020 compared to 2019. Considering different cancer staging systems, we divided tumors into early stages and advanced stages, using pathological outcomes. Furthermore, to assess the impact of the COVID-19 pandemic on surgical outcomes, perioperative data of both 2020 and 2019 were also examined. RESULTS: Overall, a total of 8250 patients, 4370 (53%) and 3880 (47%) were surgically treated during 2019 and 2020 respectively, in 62 Italian surgical Units. In 2020, the rate of patients treated with an advanced pathological stage was not different compared to 2019 (P = 0.25). Nevertheless, the analysis of quarters revealed that in the second half of 2020 the rate of advanced cancer resected, tented to be higher compared with the same months of 2019 (P = 0.05). During the pandemic year 'Charlson Comorbidity Index score of cancer patients (5.38 ± 2.08 vs 5.28 ± 2.22, P = 0.036), neoadjuvant treatments (23.9% vs. 19.5%, P < 0.001), rate of urgent diagnosis (24.2% vs 20.3%, P < 0.001), colorectal cancer urgent resection (9.4% vs. 7.37, P < 0.001), and the rate of positive nodes on the total nodes resected per surgery increased significantly (7 vs 9% - 2.02 ± 4.21 vs 2.39 ± 5.23, P < 0.001). CONCLUSIONS: Although the SARS-CoV-2 pandemic did not influence the pathological stage of colorectal, gastroesophageal, and pancreatic cancers at the time of surgery, our study revealed that the pandemic scenario negatively impacted on several perioperative and post-operative outcomes.