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Joel Katz,1–3 Aliza Weinrib,1,2 Samantha R Fashler,2 Rita Katznelzon,1,3 Bansi R Shah,1 Salima SJ Ladak,1 Jiao Jiang,1 Qing Li,1 Kayla McMillan,1 Daniel Santa Mina,5,6 Kirsten Wentlandt,7 Karen McRae,1,3 Diana Tamir,1,3 Sheldon Lyn,1,3 Marc de Perrot,8 Vivek Rao,9 David Grant,10 Graham Roche-Nagle,11 Sean P Cleary,12 Stefan OP Hofer,13 Ralph Gilbert,14 Duminda Wijeysundera,1,3 Paul Ritvo,15 Tahir Janmohamed,16 Gerald O’Leary,1,3 Hance Clarke1,3 1Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, University of Toronto, 2Department of Psychology, York University, 3Department of Anesthesia, University of Toronto, 4Palliative Care, University Health Network, University of Toronto, 5Princess Margaret Cancer Centre, University Health Network, University of Toronto, 6Faculty of Kinesiology and Physical Education, University of Toronto, 7Department of Family and Community Medicine, University of Toronto, 8Division of Thoracic Surgery, Toronto General Hospital, 9Division of Cardiovascular Surgery, Toronto General Hospital, 10Multiorgan Transplant Program, Toronto General Hospital, 11Division of Vascular Surgery, Toronto General Hospital, 12Division of General Surgery, Toronto General Hospital, 13Division of Plastic Surgery, Toronto General Hospital, 14Division of Otolaryngology – Head and Neck Surgery, Toronto General Hospital, 15Department of Kinesiology and Health Science, York University, 16ManagingLife, Toronto, ON, CanadaAbstract: Chronic postsurgical pain (CPSP), an often unanticipated result of necessary and even life-saving procedures, develops in 5–10% of patients one-year after major surgery. Substantial advances have been made in identifying patients at elevated risk of developing CPSP based on perioperative pain, opioid use, and negative affect, including depression, anxiety, pain catastrophizing, and posttraumatic stress disorder-like symptoms. The Transitional Pain Service (TPS) at Toronto General Hospital (TGH) is the first to comprehensively address the problem of CPSP at three stages: 1) preoperatively, 2) postoperatively in hospital, and 3) postoperatively in an outpatient setting for up to 6 months after surgery. Patients at high risk for CPSP are identified early and offered coordinated and comprehensive care by the multidisciplinary team consisting of pain physicians, advanced practice nurses, psychologists, and physiotherapists. Access to expert intervention through the Transitional Pain Service bypasses typically long wait times for surgical patients to be referred and seen in chronic pain clinics. This affords the opportunity to impact patients' pain trajectories, preventing the transition from acute to chronic pain, and reducing suffering, disability, and health care costs. In this report, we describe the workings of the Transitional Pain Service at Toronto General Hospital, including the clinical algorithm used to identify patients, and clinical services offered to patients as they transition through the stages of surgical recovery. We describe the role of the psychological treatment, which draws on innovations in Acceptance and Commitment Therapy that allow for brief and effective behavioral interventions to be applied transdiagnostically and preventatively. Finally, we describe our vision for future growth. Keywords: Transitional Pain Service, chronic postsurgical pain, transition to chronic pain, opioid use, multidisciplinary treatment

Background: Pancreatoduodenectomy (PD) for pancreatic cancer has a profound impact on patients' lives. However, the long-term financial implications are poorly understood., Objective: Assess the financial burden of long-term survivors who underwent PD., Methods: Patients who underwent PD between January 2011 and June 2019 were identified. To evaluate the long-term financial burden, patients surviving ≥ 3 years post-resection were prospectively surveyed using the Comprehensive Score for financial Toxicity (COST-FACIT) and a customized institutionally developed questionnaire. A logistic regression model predicting high financial toxicity was used to identify predictive factors., Results: Among 238 eligible patients, 137 (57.6%) responded. Responders had a median age of 66 (59-73) years, with 86.7% identifying as financial prosperous or comfortable. However, 33.3% experienced financial distress due to treatment costs, 27.3% demonstrated high financial toxicity on the COST-FACIT survey, and 37.2% made sacrifices to afford treatment. Only 8.9% stated that the treatment costs influenced their decisions, and the majority (85.9%) did not discuss financial implications with healthcare providers. Multivariable analysis identified younger age as a risk factor for high financial toxicity., Conclusion: One in three long-term survivors experienced high financial toxicity, with younger age being a predictor. This emphasizes the need for efforts to provide comprehensive support and guidance to patients to navigate their oncological journey., (© 2024 Wiley Periodicals LLC.)

Background: Metastasis or recurrence of pancreatic neuroendocrine tumors (pNETs) after pancreatectomy is an important source of postsurgical morbidity. This study aimed to define disease-free survival (DFS) in this population., Methods: Patients who underwent pancreatectomy for pNETs between January 2005 and January 2022 were included. Clinicopathologic and survival data were collected, and the primary endpoint was DFS. Kaplan-Meier survival analysis and Cox proportional hazards regression modeling were performed., Results: Of the 223 patients, 144 (65%) distal/subtotal/partial pancreatectomies, 71 (32%) pancreaticoduodenectomies, 6 (3%) total pancreatectomies, and 2 (1%) enucleations were performed. Of the 223 patients, 45 (20%) experienced disease recurrence or metastasis after index pancreatectomy during the 17 years of the study. Nonfunctional pNETs (162 [73%]) were more common than hormonally functional subtypes. The 2- and 5-year DFSs were 82% and 76%, respectively. Kaplan-Meier analysis demonstrated that N1 node positive disease, size of ≥ 4 cm, lymphovascular invasion, perineural invasion, Ki-67 of ≥ 20%, and nonfunctional pNETs are significantly associated with a lower DFS (P < .05). Univariate Cox analysis identified the following predictors to be significantly associated with poorer DFS: larger tumor size (hazard ratio [HR], 1.16; 95% CI, 1.04-1.28), Ki-67 index of ≥ 20% (HR, 4.93; 95% CI, 2.00-11.44), perineural invasion (HR, 3.23; 95% CI, 1.40-7.89), open surgery (HR, 3.34; 95% CI, 1.03-1.33), node-positive disease (HR, 5.27; 95% CI, 2.28-13.26), and increased body mass index (HR, 1.10; 95% CI, 1.03-1.17) (P < .05)., Conclusion: Of note, 1 in 5 patients who underwent resection developed recurrence or metastasis after pancreatectomy. Prognostic predictors of DFS in pNETs could help optimize treatment and enhance follow-up protocols to improve quality and reduce morbidity., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Background: Surgical cytoreduction for neuroendocrine tumor liver metastasis (NETLM) consistently shows positive long-term outcomes. Despite reservations in guidelines for surgery when the primary tumor is unidentified (UP-NET), this study compared the surgical and oncologic long-term outcomes between patients with these rare cases undergoing cytoreductive surgery and patients who had liver resection for known primaries., Methods: The study identified 32 unknown primary liver metastases (UP-NETLM) in 522 retrospectively evaluated patients who underwent resection of well-differentiated NETLM between January 2000 and December 2020. Tumor and patient characteristics were compared with those in 490 cases of liver metastasis from small intestinal (SI-NETLM) or pancreatic (pNETLM) primaries. Survival analysis was performed to highlight long-term outcome differences. Surgical outcomes were compared between liver resections alone and simultaneous primary resections to assess surgical risk distinctions., Results: The UP-NET patients had fewer NETLMs (p = 0.004), which on the average were larger than SI-NETLMs or pNETLMs (p = 0.002). Expression of Ki-67 was balanced among the groups. Major hepatectomy was performed more often in the UP-NETLM group (p = 0.017). The 10-year survival rate of 53% for UP-NETLM was comparable with that for SI-NETML (58%; p = 0.463) and pNETLMs (47%; p = 0.497). The median hepatic progression-free survival was 26 months for the UP-NETLM patients and 25 months for the SI-NETLM patients compared to 12 months for the pNETLM patients (p < 0.001). Perioperative mortality was lower than 2%, and severe postoperative morbidity occurred in 21%, similarly distributed among all the groups., Conclusion: The surgical risk and long-term outcomes for the UP-NETLM patients were comparable with those for other NETLM cases, affirming the validity of equally aggressive surgical cytoreduction as a therapeutic option in carefully selected cases., (© 2024. Society of Surgical Oncology.)

Background: Cytoreductive hepatectomy can improve survival and symptoms of hormonal excess in patients with small intestinal neuroendocrine tumor (siNET) liver metastases, but whether to proceed when peritoneal metastases are encountered at the time of planned cytoreductive hepatectomy is controversial., Methods: This was a retrospective review of patients who underwent surgical management of metastatic siNETs at Mayo Clinic between 2000 and 2020. Patients who underwent cytoreductive operation for isolated liver metastases or both liver and peritoneal metastases were compared., Results: Of 261 patients who underwent cytoreductive operation for siNETs, 211 had isolated liver metastases and 50 had liver and peritoneal metastases. Complete cytoreduction was achieved in 78% of patients with isolated liver metastases and 56% of those with liver and peritoneal metastases (p = 0.002). After complete cytoreduction, median overall survival (OS) was 11.5 years for isolated liver metastases and 11.2 years for liver and peritoneal metastases (p = 0.10), and relief of carcinoid syndrome was ≥ 97% in both groups. After incomplete cytoreduction with debulking of > 90% of hepatic disease and/or closing Lyon score of 1-2, median OS was 6.4 years for isolated liver metastases and 7.1 years for liver and peritoneal metastases (p = 0.12)., Conclusions: Patients with siNETs metastatic to both the liver and peritoneum have favorable outcomes after aggressive surgical cytoreduction, with the best outcomes observed after complete cytoreduction. Therefore, the presence of peritoneal metastases should not by itself preclude surgical cytoreduction in this population., (© 2024. Society of Surgical Oncology.)

Biliary tract cancers, including cholangiocarcinoma, gallbladder, and ampulla of Vater cancers, rank second among hepatobiliary cancers, known for their poor prognoses. The United States has witnessed a notable increase in intrahepatic cholangiocarcinoma incidence. This study examines the incidence and survival outcomes of biliary tract cancers in Olmsted County, Minnesota from 1976 to 2018. Using data from the Rochester Epidemiology Project (REP), residents aged 20 and above were analyzed across four eras. Incidence rates were calculated and adjusted for age and sex, and temporal trends were assessed using Poisson regression. Intrahepatic cholangiocarcinoma exhibited a significant escalation in incidence rates over time, while gallbladder cancers showed a decline among women. Median survival times for biliary tract cancers notably improved. These findings confirm the rising incidence of intrahepatic cholangiocarcinoma and suggest improving survival rates. Nevertheless, the overall prognosis for biliary tract cancers remains very poor, emphasizing the continual need for enhanced management strategies and further research.

Background and Aims: Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European descent populations (EDP)., Approach and Results: We conducted a 2-stage genome-wide association study (GWAS) on HCC not affected by HBV infections. A total of 1872 HCC cases and 2907 controls were included in the discovery stage, and 1200 HCC cases and 1832 controls in the validation. We analyzed the discovery and validation samples separately and then conducted a meta-analysis. All analyses were conducted in the presence and absence of HCV. The liability-scale heritability was 24.4% for overall HCC. Five regions with significant ORs (95% CI) were identified for nonviral HCC: 3p22.1, MOBP , rs9842969, (0.51, [0.40-0.65]); 5p15.33, TERT , rs2242652, (0.70, (0.62-0.79]); 19q13.11, TM6SF2 , rs58542926, (1.49, [1.29-1.72]); 19p13.11 MAU2 , rs58489806, (1.53, (1.33-1.75]); and 22q13.31, PNPLA3 , rs738409, (1.66, [1.51-1.83]). One region was identified for HCV-induced HCC: 6p21.31, human leukocyte antigen DQ beta 1, rs9275224, (0.79, [0.74-0.84]). A combination of homozygous variants of PNPLA3 and TERT showing a 6.5-fold higher risk for nonviral-related HCC compared to individuals lacking these genotypes. This observation suggests that gene-gene interactions may identify individuals at elevated risk for developing HCC., Conclusions: Our GWAS highlights novel genetic susceptibility of nonviral HCC among European descent populations from North America with substantial heritability. Selected genetic influences were observed for HCV-positive HCC. Our findings indicate the importance of genetic susceptibility to HCC development., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The management of invasive intraductal papillary mucinous cystic neoplasm (I-IPMN) does not differ from de novo pancreatic ductal adenocarcinoma (PDAC); however, I-IPMNs are debated to have better prognosis. Despite being managed similarly to PDAC, no data are available on the response of I-IPMN to neoadjuvant chemotherapy., Methods: All patients undergoing pancreatic resection for a pancreatic adenocarcinoma from 2011 to 2022 were included. The PDAC and I-IPMN cohorts were compared to evaluate response to neoadjuvant therapy (NAT) and overall survival (OS)., Results: This study included 1052 PDAC patients and 105 I-IPMN patients. NAT was performed in 25% of I-IPMN patients and 65% of PDAC patients. I-IPMN showed a similar pattern of pathological response to NAT compared with PDAC (p = 0.231). Furthermore, positron emission tomography (PET) response (71% vs. 61%; p = 0.447), CA19.9 normalization (85% vs. 76%, p = 0.290), and radiological response (32% vs. 37%, p = 0.628) were comparable between I-IPMN and PDAC. A significantly higher OS and disease-free survival (DFS) of I-IPMN was denoted by Kaplan-Meier analysis, with a p-value of < 0.001 in both plots. In a multivariate analysis, I-IPMN histology was independently associated with lower risk of recurrence and death., Conclusions: I-IPMN patients have a longer OS and DFS after surgical treatment when compared with PDAC patients. The more favorable oncologic outcome of I-IPMNs does not seem to be related to early detection, as I-IPMN histological subclass is independently associated with a lower risk of disease recurrence. Moreover, neoadjuvant effect on I-IPMN was non-inferior to PDAC in terms of pathological, CA19.9, PET, and radiological response and thus can be considered in selected patients., (© 2024. The Author(s).)

Escherichia coli Septu system, an anti-phage defense system, comprises two components: PtuA and PtuB. PtuA contains an ATPase domain, while PtuB is predicted to function as a nuclease. Here we show that PtuA and PtuB form a stable complex with a 6:2 stoichiometry. Cryo-electron microscopy structure of PtuAB reveals a distinctive horseshoe-like configuration. PtuA adopts a hexameric arrangement, organized as an asymmetric trimer of dimers, contrasting the ring-like structure by other ATPases. Notably, the three pairs of PtuA dimers assume distinct conformations and fulfill unique roles in recruiting PtuB. Our functional assays have further illuminated the importance of the oligomeric assembly of PtuAB in anti-phage defense. Moreover, we have uncovered that ATP molecules can directly bind to PtuA and inhibit the activities of PtuAB. Together, the assembly and function of the Septu system shed light on understanding other ATPase-containing systems in bacterial immunity., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Hepatopancreatobiliary (HPB) surgery requires specialized training and adequate case volumes to maintain procedural proficiency and optimal outcomes. Studies of individual HPB surgeon supply related to annual HPB case demand are sparse. This study assesses the supply and demand of the HPB surgical workforce in the United States (US)., Methods: The National Inpatient Sample (NIS) was queried from 1998-2019 to estimate the number of HPB procedures performed. To approximate the number of HPB surgeons, models based on previous HPB workforce publications were employed. We then calculated the number of HPB surgeons needed to maintain volume-outcome thresholds at current reported levels of centralization., Results: In 2019, approximately 37,335 patients underwent inpatient HPB procedures in the US, while an estimated 905-1191 HPB surgeons were practicing. Assuming 50% centralization and an optimal volume-outcome threshold of 24 HPB cases-per-year, only 778 HPB surgeons were needed. Without adjustment in centralization, by 2030 there will be a demand of fewer than 12 annual cases per HPB surgeon., Conclusion: The current supply of HPB surgeons may exceed demand in the United States. Without alteration in training pathways or improved care centralization, by 2030, there will be insufficient HPB case volume per surgeon to maintain published volume-outcome standards., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Pancreatic ductal adenocarcinoma (PDAC) impacts patients in their 60s, but its incidence in younger patients is increasing. We hypothesize that younger patients may have worse oncologic outcomes., Methods: Patients who underwent curative pancreatic resection for PDAC between January 2011 and December 2021 at a single institution were analyzed. Early-onset pancreatic cancer (EOPC) was defined as pancreatic cancer diagnosed in patients ≤50 years. Clinical and survival outcomes were compared between EOPC and Conventional Onset Pancreas Cancer (COPC)., Results: A total of 1133 patients were identified, 65 (5.7%) were EOPC. Preoperative patient characteristics including sex, smoking status, alcohol habitus, diabetes mellitus, CA 19-9, and neoadjuvant therapy were similar between EOPC and COPC (p > 0.05). EOPC patients were more likely non-white (p = 0.03), had lower ASA scores (p = 0.02) and larger median tumor size (33 vs 28 mm, p = 0.04), but had similar pathological stages and rate of R0 resections (p > 0.05). Postoperative outcomes were similar (p > 0.05). There was no statistically significant difference in overall (HR 0.93, CI 0.64, 1.33; p = 0.68) or recurrence free (HR 1.05, CI 0.75, 1.48; p = 0.77) survival between the EOPC and COPC after adjusting for significant factors., Conclusion: Patients with EOPC who underwent surgical resection had similar oncological outcomes compared to patients with COPC., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Minimally invasive approaches to liver resection (MILR) are associated with favorable outcomes. The aim of this study was to determine the implications of conversion to an open procedure on perioperative outcomes., Methods: Patients who underwent MILR at 10 North American institutions were identified from the Americas Minimally Invasive Liver Resection (AMILES) database. Outcomes of patients who required conversion were compared to those who did not. Additionally, outcomes after conversion due to unfavorable findings (poor visualization/access, lack of progress, disease extent) versus intraoperative events (bleeding, injury, cardiopulmonary instability) were compared., Results: Of 1675 patients who underwent MILR, 102 (6.1%) required conversion. Conversion rate ranged from 4.4% for left lateral sectionectomy to 10% for right hepatectomy. The primary reason for conversion was unfavorable findings in 67 patients (66%) and intraoperative adverse events in 35 patients (34%). By multivariable analysis, major resection, cirrhosis, prior liver surgery, and tumor proximity to major vessels were identified as risk factors for conversion (p < 0.05). Patients who required conversion had higher blood loss, transfusion requirements, operative time, and length of stay, (p < 0.05). They also had higher major complication rates (23% vs. 5.2%, p < 0.001) and 30-day mortality (8.8% vs. 1.3%, p < 0.001). When compared to those who required conversion due to unfavorable findings, patients who required conversion due to intraoperative adverse events had significantly higher major complication rates (43% vs. 14%, p = 0.012) and 30-day mortality (20% vs. 3.0%, p = 0.007)., Conclusions: Conversion from MILR to open surgery is associated with increased perioperative morbidity and mortality. Conversion due to intraoperative adverse events is rare but associated with significantly higher complication and mortality rates, while conversion due to unfavorable findings is associated with similar outcomes as planned open resection. High-risk patients may benefit from early conversion in a controlled fashion if difficulties are encountered or anticipated., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Data regarding oncologic outcomes of segmental bile duct resection (SBDR) versus pancreatoduodenectomy (PD) for bile duct cancers (BDC) are conflicting. We compared SBDR and PD for BDC utilizing pooled data analysis., Materials and Methods: A comprehensive PRISMA 2020 systematic review was performed. Studies comparing SBDR with PD for BDC were included. Pooled mean differences (MD), odds ratios (OR), and risk ratios (RR) with 95% confidence intervals (CI) were calculated. Subgroup analyses were performed. Study quality, bias, heterogeneity, and certainty were analyzed., Results: Twelve studies from 2004 to 2021 were included, comprising 533 SBDR and 1,313 PD. SBDR was associated with positive proximal duct margins (OR 1.56; CI 1.11-2.18; P = .01), and distal duct margins (OR 43.25; CI 10.38-180.16; P < .01). SBDR yielded fewer lymph nodes (MD -6.93 nodes; CI -9.72-4.15; P < .01) and detected fewer nodal metastases (OR 0.72; CI 0.55-0.94; P = .01). SBDR portended less perioperative morbidity (OR 0.31; CI 0.21-0.46; P < .01), but not mortality (OR 0.52; CI 0.20-1.32; P = .17). SBDR was associated with locoregional recurrences (OR 1.88; CI 1.01-3.53; P = .02), and lymph node recurrences (OR 2.13; CI 1.42-3.2; P = .04). SBDR yielded decreased 5-year OS (OR 0.75; CI 0.65-0.85; P < .01)., Conclusions: Despite decreased perioperative morbidity, SBDR appears to provide inferior oncologic control for BDC., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: Racial and gender biases exist within academic surgery; bias negatively impacts patient care, reimbursement, student training, and staff retention. Few studies have investigated the potential for bias in surgical fellowship recruitment. We aimed to compare the racial and gender diversity at our hepatopancreatobiliary (HPB) surgery fellowship program to nationwide standards. We further aimed to investigate differences in the demographics of resident interviewees versus matriculants to our HPB fellowship., Design: Retrospective review., Setting: North American HPB fellowship training programs., Participants: Mayo Clinic's HPB surgery fellowship interviewees and North American HPB surgery fellowship graduates from 2013 to 2020., Results: When compared to general surgery residency graduates during the study period (in 2019), a lower proportion of North American HPB surgery fellowship graduates were female (26% HPB fellowship graduates vs. 43.1% residents, p = 0.005), with no difference in proportion of racially under-represented in medicine (rURM) HPB fellowship graduates (10.7%) compared to rURM proportion of general surgery residents nationally (14.5%). There was an upward trend in female representation among North American HPB fellowship graduates from 11% in 2013 to 32% in 2020, but proportions of rURM HPB fellows remained steadily low. When comparing HPB interviewees at our institution to national general surgery residents, no differences were observed in proportions of female (34.4% interviewees vs. 43.1% residents, p = 0.17) or rURM (interviewees = 6.8%, residents = 14.5%, p = 0.09) applicants. Additionally, there was no significant difference between the proportion of female or rURM interviewees and matriculants to our HPB program., Conclusions: While fewer female graduating surgeons are pursuing HPB fellowship training than male graduates, this gender gap has narrowed over time. In contrast, the national percentage of rURM HPB fellowship graduates has remained low, mirroring stagnant proportions of rURM surgical residency graduates. When comparing HPB fellowship interviewees at our own institution to North American fellowship graduates, we observed similar proportions of female interviewees but lower proportions of rURM interviewees. Locally, these data will drive process change toward more intentional examination of our interview selection process. Nationally, more work is needed to increase the racial diversity of surgical residency and fellowship trainees to best reflect and serve our diverse patient populations., (Copyright © 2023 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Peritoneal metastases (PM) from pancreatic ductal adenocarcinoma (PDAC) are currently treated with palliative systemic chemotherapy alone, with unsatisfactory results. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may provide an oncologic benefit for highly selected patients., Patients and Methods: Patients with PDAC and isolated PM who completed ≥ 6 months of systemic chemotherapy with objective response between 2017 and 2022 were retrospectively reviewed. All patients met the inclusion/exclusion criteria as per our previously published PDAC CRS/HIPEC protocol. Patients who underwent CRS/HIPEC were compared with matched patients who underwent systemic therapy alone. Overall survival (OS) from diagnosis of PM and progression-free survival (PFS) from CRS/HIPEC was evaluated., Results: In total, 61 patients met the inclusion criteria: 38 underwent systemic therapy alone and 23 CRS/HIPEC. There were no differences in baseline prognostic factors, including age, sex, tumor size, tumor location, anatomic resectability, or serum cancer antigen (CA) 19-9 (p > 0.05). Median OS from PM diagnosis in patients who underwent systemic therapy alone was 19 months with 1, 2, and 3 year OS of 81%, 31%, and 8%, respectively. In contrast, median OS from PM diagnosis in patients who underwent CRS/HIPEC was 41 months with improved 1, 2, and 3 year OS of 91%, 66%, and 59%, respectively (p = 0.002). In the 21 patients who achieved complete cytoreduction (CC-0), no adjuvant therapy was administered and the median PFS was 17 months., Conclusions: CRS/HIPEC in highly selected patients with PDAC and PM results in promising oncologic outcomes that are unlikely to be achieved with systemic chemotherapy alone. Further investigation is warranted and ongoing (NCT04858009)., (© 2023. Society of Surgical Oncology.)

Objective: This study aims at establishing benchmark values for best achievable outcomes following open major anatomic hepatectomy for liver tumors of all dignities., Background: Outcomes after open major hepatectomies vary widely lacking reference values for comparisons among centers, indications, types of resections, and minimally invasive procedures., Methods: A standard benchmark methodology was used covering consecutive patients, who underwent open major anatomic hepatectomy from 44 high-volume liver centers from 5 continents over a 5-year period (2016-2020). Benchmark cases were low-risk non-cirrhotic patients without significant comorbidities treated in high-volume centers (≥30 major liver resections/year). Benchmark values were set at the 75th percentile of median values of all centers. Minimum follow-up period was 1 year in each patient., Results: Of 8044 patients, 2908 (36%) qualified as benchmark (low-risk) cases. Benchmark cutoffs for all indications include R0 resection ≥78%; liver failure (grade B/C) ≤10%; bile leak (grade B/C) ≤18%; complications ≥grade 3 and CCI ® ≤46% and ≤9 at 3 months, respectively. Benchmark values differed significantly between malignant and benign conditions so that reference values must be adjusted accordingly. Extended right hepatectomy (H1, 4-8 or H4-8) disclosed a higher cutoff for liver failure, while extended left (H1-5,8 or H2-5,8) were associated with higher cutoffs for bile leaks, but had superior oncologic outcomes, when compared to formal left hepatectomy (H1-4 or H2-4). The minimal follow-up for a conclusive outcome evaluation following open anatomic major resection must be 3 months., Conclusion: These new benchmark cutoffs for open major hepatectomy provide a powerful tool to convincingly evaluate other approaches including parenchymal-sparing procedures, laparoscopic/robotic approaches, and alternative treatments, such as ablation therapy, irradiation, or novel chemotherapy regimens., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Open combined resections of colorectal primary tumors and synchronous liver metastases have become common in selected cases. However, evidences favoring a minimally invasive (MIS) approach are still limited. The aim of this study is to evaluate the outcomes of MIS vs. open synchronous liver and colorectal resections., Methods: 384 cases of synchronous colorectal and liver resections performed at one institution were identified during the study period. MIS vs open approach were compared after a propensity score matching; surgical outcomes were analyzed., Results: MIS cases featured longer operative time (399 vs 300 min, p < 0.001), fewer blood loss (200 vs 500 ml, p = 0.003), and shorter hospitalization (median LOS 4 vs 6 days, p = 0.001). No difference was observed between the two groups for use of Pringle maneuver (p = 0.083), intraoperative blood transfusion (p = 0.061), achievement of negative colorectal (p = 0.176) and liver margins (p = 1.000), postoperative complications (p = 1.000) and significant (Clavien-Dindo ≥ 3a) complications (p = 0.817), delay of adjuvant therapy due to complications (p = 0.555), 30- and 90-day mortality., Conclusion: Synchronous colorectal and liver metastases resections via a minimally-invasive approach in high-volume centers with appropriate expertise result in significantly lower blood loss and length of stay despite longer operative time in comparison to open, with no oncological inferiority., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Objective and Background: Clinically significant posthepatectomy liver failure (PHLF B+C) remains the main cause of mortality after major hepatic resection. This study aimed to establish an APRI+ALBI, aspartate aminotransferase to platelet ratio (APRI) combined with albumin-bilirubin grade (ALBI), based multivariable model (MVM) to predict PHLF and compare its performance to indocyanine green clearance (ICG-R15 or ICG-PDR) and albumin-ICG evaluation (ALICE)., Methods: 12,056 patients from the National Surgical Quality Improvement Program (NSQIP) database were used to generate a MVM to predict PHLF B+C. The model was determined using stepwise backwards elimination. Performance of the model was tested using receiver operating characteristic curve analysis and validated in an international cohort of 2,525 patients. In 620 patients, the APRI+ALBI MVM, trained in the NSQIP cohort, was compared with MVM's based on other liver function tests (ICG clearance, ALICE) by comparing the areas under the curve (AUC)., Results: A MVM including APRI+ALBI, age, sex, tumor type and extent of resection was found to predict PHLF B+C with an AUC of 0.77, with comparable performance in the validation cohort (AUC 0.74). In direct comparison with other MVM's based on more expensive and time-consuming liver function tests (ICG clearance, ALICE), the APRI+ALBI MVM demonstrated equal predictive potential for PHLF B+C. A smartphone application for calculation of the APRI+ALBI MVM was designed., Conclusion: Risk assessment via the APRI+ALBI MVM for PHLF B+C increases preoperative predictive accuracy and represents an universally available and cost-effective risk assessment prior to hepatectomy, facilitated by a freely available smartphone app., Competing Interests: Disclosure of Conflicts: Patrick Starlinger and Johannes Starlinger were involved in the development of a freely available smartphone-first application (TELLAPRIALBI, https://tellaprialbi.howto.health), all other authors have no conflict of interest to declare., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Most patients with intrahepatic cholangiocarcinoma (IHCC) develop recurrence after resection. Adjuvant capecitabine remains the standard of care for resected IHCC. A combination of gemcitabine, cisplatin, and nab-paclitaxel (GAP) was associated with a 45% response rate and 20% conversion rate among patients with unresectable biliary tract cancers. The aim of this study was to evaluate the feasibility of delivering GAP in the neoadjuvant setting for resectable, high-risk IHCC., Methods: A multi-institutional, single-arm, phase II trial was conducted for patients with resectable, high-risk IHCC, defined as tumor size > 5 cm, multiple tumors, presence of radiographic major vascular invasion, or lymph node involvement. Patients received preoperative GAP (gemcitabine 800 mg/m 2 , cisplatin 25 mg/m 2 , and nab-paclitaxel 100 mg/m 2 on days 1 and 8 of a 21-day cycle) for a total of 4 cycles prior to an attempt at curative-intent surgical resection. The primary endpoint was completion of both preoperative chemotherapy and surgical resection. Secondary endpoints were adverse events, radiologic response, recurrence-free survival (RFS), and overall survival (OS)., Results: Thirty evaluable patients were enrolled. Median age was 60.5 years. Median follow-up for all patients was 17 months. Ten patients (33%) experienced grade ≥ 3 treatment-related adverse events, the most common being neutropenia and diarrhea; 50% required ≥ 1 dose reduction. The disease control rate was 90% (progressive disease: 10%, partial response: 23%, stable disease: 67%). There was zero treatment-related mortality. Twenty-two patients (73%, 90% CI 57-86; p = 0.008) completed all chemotherapy and surgery. Two patients (9%) who successfully underwent resection had minor postoperative complications. Median length of hospital stay was 4 days. Median RFS was 7.1 months. Median OS for the entire cohort was 24 months and was not reached in patients who underwent surgical resection., Conclusion: Neoadjuvant treatment with gemcitabine, cisplatin, and nab-paclitaxel is feasible and safe prior to resection of intrahepatic cholangiocarcinoma and does not adversely impact perioperative outcomes., (© 2023. Society of Surgical Oncology.)

Charge detection mass spectrometry (CDMS) enables the direct mass measurement of heterogeneous samples on the megadalton scale, as the charge state for a single ion is determined simultaneously with the mass-to-charge ratio ( m / z ). Surface-induced dissociation (SID) is an effective activation method to dissociate non-intertwined, non-covalent protein complexes without extensive gas-phase restructuring, producing various subcomplexes reflective of the native protein topology. Here, we demonstrate that using CDMS after SID on an Orbitrap platform offers subunit connectivity, topology, proteoform information, and relative interfacial strengths of the intact macromolecular assemblies. SID dissects the capsids (∼3.7 MDa) of adeno-associated viruses (AAVs) into trimer-containing fragments (3mer, 6mer, 9mer, 15mer, etc.) that can be detected by the individual ion mass spectrometry (I2MS) approach on Orbitrap instruments. SID coupled to CDMS provides unique structural insights into heterogeneous assemblies that are not readily obtained by traditional MS measurements.

Background: Post-operative pancreatic fluid collections (POPFCs) can be drained using percutaneous or endoscopic approaches. The primary aim of this study was to compare rates of clinical success between endoscopic ultrasound-guided drainage (EUSD) with percutaneous drainage (PTD) in the management of symptomatic POPFCs after distal pancreatectomy. Secondary outcomes included technical success, total number of interventions, time to resolution, rates of adverse events (AEs), and POPFC recurrence., Methods: Adults who underwent distal pancreatectomy from January 2012 to August 2021 and developed symptomatic POPFC in the resection bed were retrospectively identified from a single academic center database. Demographic data, procedural data, and clinical outcomes were abstracted. Clinical success was defined as symptomatic improvement and radiographic resolution without requiring an alternate drainage modality. Quantitative variables were compared using a two-tailed t-test and categorical data were compared using Chi-squared or Fisher's exact tests., Results: Of 1046 patients that underwent distal pancreatectomy, 217 met study inclusion criteria (median age 60 years, 51.2% female), of whom 106 underwent EUSD and 111 PTD. There were no significant differences in baseline pathology and POPFC size. PTD was generally performed earlier after surgery (10 vs. 27 days; p < 0.001) and more commonly in the inpatient setting (82.9% vs. 49.1%; p < 0.001). EUSD was associated with a significantly higher rate of clinical success (92.5% vs. 76.6%; p = 0.001), fewer median number of interventions (2 vs. 4; p < 0.001), and lower rate of POPFC recurrence (7.6% vs. 20.7%; p = 0.007). AEs were similar between EUSD (10.4%) and PTD (6.3%, p = 0.28), with approximately one-third of EUSD AEs due to stent migration., Conclusion: In patients with POPFCs after distal pancreatectomy, delayed drainage with EUSD was associated with higher rates of clinical success, fewer interventions, and lower rates of recurrence than earlier drainage with PTD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Distant metastases are the strongest predictor of poor prognosis for patients with neuroendocrine tumors (NETs). Cytoreductive hepatectomy (CRH) can relieve symptoms of hormonal excess and prolong survival for patients with liver metastases (NETLMs), but long-term outcomes are poorly characterized., Methods: This retrospective single-institution analysis analyzed patients who underwent CRH for well-differentiated NETLMs from 2000 to 2020. Kaplan-Meier analysis estimated symptom-free interval and overall and progression-free survival. Multivariable Cox regression analysis evaluated factors associated with survival., Results: The inclusion criteria were met by 546 patients. The most common primary sites were the small intestine (n = 279) and the pancreas (n = 194). Simultaneous primary tumor resection was performed for 60 % of the cases. Major hepatectomy comprised 27% of the cases, but this rate decreased during the study period (p < 0.001). Major complications occurred in 20%, and the 90-day mortality rate was 1.6%. Functional disease was present in 37 %, and symptomatic relief was achieved in 96%. The median symptom-free interval was 41 months (62 months after complete cytoreduction and 21 months with gross residual disease) (p = 0.021). The median overall survival was 122 months, and progression-free survival was 17 months. In the multivariable analysis, worse overall survival was associated with age, pancreatic primary tumor, Ki-67, number and size of lesions, and extrahepatic metastases, with Ki-67 as the strongest predictor (odds ratio [OR], 1.90 for Ki-67 [3-20%; p = 0.018] and OR, 4.25 for Ki-67 [>20%; p < 0.001])., Conclusion: The study showed that CRH for NETLMs is associated with low perioperative morbidity and mortality and excellent overall survival, although the majority will experience recurrence/progression. For patients with functional tumors, CRH can provide durable symptomatic relief., (© 2023. The Author(s).)

Background: Portal or superior mesenteric vein (PV-SMV) resection and reconstruction is sometimes required during pancreatic tumor resection. In patients requiring segmental venous resection with interposition grafting, the left renal vein (LRV) is an accessible autologous solution. However, long-term patency outcomes of the LRV as an interposition conduit in this setting have not been analyzed., Study Design: We conducted a retrospective analysis of patients undergoing pancreatic resection with PV-SMV reconstruction using LRV between 2002 and 2022. The primary outcome was PV-SMV patency at last follow-up, assessed with postoperative CT scans and analyzed using Kaplan-Meier survival methods that account for variation in follow-up duration. Development of any postoperative acute kidney injury within 7 days of surgery and morbidity were secondary outcomes., Results: The study cohort includes 65 patients who underwent LRV harvest; 60 (92%) ultimately underwent successful reconstruction with harvested LRV graft. Kaplan-Meier 2-year estimated patency rate of the LRV graft was 88%, with no cases of complete occlusion. Six (10%) patients experienced graft stenosis. Nine of 61 (15%) patients experienced grade II or III acute kidney injury, 6 of 9 returning to normal renal function before discharge. No difference in median serum creatinine was observed at baseline, 6 and 12 months from surgery. LRV remnant thrombosis was seen in 7 of 65 (11%) patients. Only 3 of 61 (5%) patients had persistent acute kidney injury caused by complications unrelated to LRV harvesting., Conclusions: Autologous LRV graft was a reliable conduit for segmental PV-SMV reconstruction, resulting in a high patency rate and marginal impact on renal function. LRV harvest is a safe and potentially ideal surgical option for PV-SMV reconstruction in pancreatic surgery., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Accurate staging prior to resection of pancreatic ductal adenocarcinoma (PDAC) is imperative to avoid unnecessary operative morbidity and oncologic futility in patients with occult intra-abdominal distant metastases. We aimed to determine the diagnostic yield of staging laparoscopy (SL) and to identify factors associated with increased risk of positive laparoscopy (PL) in the modern era., Study Design: Patients with radiographically localized PDAC who underwent SL from 2017 to 2021 were retrospectively reviewed. The yield of SL was defined as the proportion of patients with PL, including gross metastases and/or positive peritoneal cytology. Factors associated with PL were assessed using univariate analysis and multivariable logistic regression., Results: Of 1,004 patients who underwent SL, 180 (18%) had PL due to gross metastases (n = 140) and/or positive cytology (n = 96). Patients who had neoadjuvant chemotherapy prior to laparoscopy had lower rates of PL (14% vs 22%, p = 0.002). When the analysis was restricted to chemo-naive patients who had concurrent peritoneal lavage performed, 95 of 419 patients (23%) had PL. In multivariable analysis, PL was associated with younger (<60) age, indeterminate extrapancreatic lesions on preoperative imaging, body/tail tumor location, larger tumor size, and elevated serum CA 19-9 (all p < 0.05). Among patients with no indeterminate extrapancreatic lesions on preoperative imaging, the rate of PL ranged from 1.6% in patients with no risk factors to 42% in young patients with large body/tail tumors and elevated serum CA 19-9., Conclusions: The rate of PL in patients with PDAC remains high in the modern era. SL with peritoneal lavage should be considered for the majority of patients prior to resection, specifically those with high-risk features, and ideally prior to neoadjuvant chemotherapy., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Surgeons.)

Introduction: Synchronous robotic colorectal and liver resection for metastatic colorectal cancer (mCRC) is gaining popularity. This case series describes our initial institutional experience., Methods: A retrospective study of synchronous robotic colorectal and liver resections for metastatic colorectal cancer (March 2020 to December 2021)., Results: Eight patients underwent synchronous robotic resections. The median age was 59 (45-72), and the median body mass index was 29 (20-33). Seven received neoadjuvant chemotherapy, and five rectal cancers received neoadjuvant radiotherapy. One patient had a low anterior resection with major hepatectomy, two had low anterior resection with minor hepatectomy, and one had abdominoperineal resection with major hepatectomy. One patient had a left colectomy with minor hepatectomy, and two had right colectomies with minor hepatectomy. We used five robotic 8/12 mm ports in all cases. Extraction incisions were Pfannenstiel in four patients, colostomy site in two patients, one perineal incision, and one supra-umbilical incision. The median estimated blood loss was 200 mL (25-500), and the median operative time was 448 min (374-576). There were no intra-operative complications or conversions. Five patients had the liver resection first, and two of six anastomoses were performed before the liver resection. The Median length of stay was 4 days (3-14). There were two post-operative complications, prolonged ileus and DVT, with a Clavien-Dindo complication grade of I and II, respectively. There were no readmissions or reoperations. All colorectal and liver resection margins were negative., Conclusions: Synchronous robotic colorectal and liver resection can be performed effectively utilizing one port configuration with acceptable short-term outcomes and quality of oncologic resection.

Background: Minimally invasive approach represents the gold standard for the resection of the left lateral section of the liver. Recently, the American Minimally Invasive Liver Resection (AMILES) registry has become available to track outcomes of laparoscopic and robotic liver resection in the Americas. The aim of the present study is to determine the benchmark performance of MILLS throughout the AMILES database., Methods: The AMILES registry was interrogated for cases of minimally invasive left lateral sectionectomies (MILLS). Centers with best practices according to the achievement of textbook outcomes (TOs) were identified and were used to define benchmark performances., Results: Seven institutions from US and Canada entered 1665 minimally invasive liver resections, encompassing 203 MILLS. Overall, 49% of cases of MILLS satisfied contemporarily all textbook outcomes. While all centers obtained TOs with different rates of success, the outcomes of the top-ranking centers were used for benchmarking. Benchmark performance metrics of MILLS across North America are: conversion rate ≤ 3.7%, blood loss ≤ 200 ml, OR time ≤ 199 min, transfusion rate ≤ 4.5%, complication rate ≤ 7.9%, LOS ≤ 4 days., Conclusion: Benchmark performances of MILLS have been defined on a large multi-institutional database in North America. As more institutions join the collaboration and more prospective cases accrue, benchmark for additional procedures and approaches will be defined., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Colorectal liver metastases (CRLM) occur in roughly half of patients with colorectal cancer. Minimally invasive surgery (MIS) has become an increasingly acceptable and utilized technique for resection in these patients, but there is a lack of specific guidelines on the use of MIS hepatectomy in this setting. A multidisciplinary expert panel was convened to develop evidence-based recommendations regarding the decision between MIS and open techniques for the resection of CRLM., Methods: Systematic review was conducted for two key questions (KQ) regarding the use of MIS versus open surgery for the resection of isolated liver metastases from colon and rectal cancer. Evidence-based recommendations were formulated using the GRADE methodology by subject experts. Additionally, the panel developed recommendations for future research., Results: The panel addressed two KQs, which pertained to staged or simultaneous resection of resectable colon or rectal metastases. The panel made conditional recommendations for the use of MIS hepatectomy for both staged and simultaneous resection when deemed safe, feasible, and oncologically effective by the surgeon based on the individual patient characteristics. These recommendations were based on low and very low certainty of evidence., Conclusions: These evidence-based recommendations should provide guidance regarding surgical decision-making in the treatment of CRLM and highlight the importance of individual considerations of each case. Pursuing the identified research needs may help further refine the evidence and improve future versions of guidelines for the use of MIS techniques in the treatment of CRLM., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Data regarding laparoscopic liver resections(LLRs) for Gallbladder cancer(GBC) and Intrahepatic Cholangiocarcinoma(iCCA) are sparse. This study compared LLRs with open liver resections(OLRs) in a high-volume center., Methods: Data of patients who underwent LLR or OLR for GBC or iCCA at Mayo-Clinic between 01/2016 and 04/2021 were retrospectively compared. Proportional hazards models were used to compare the approach on survival., Results: 32 and 52 patients underwent LLR and OLR during the study period, respectively. 64 and 20 patients had iCCA and GBC, respectively. LLR had lower median blood loss (250 mL vs. 475 mL, p = 0.001) and shorter median length of stay compared to OLR (3.0 days vs. 6.0 days, p = 0.001). LLR and OLR did not differ in post-operative major complication (25% vs. 32.7%, p = 0.62), negative margin (100% vs. 90.4%, p = 0.15) and completeness of lymphadenectomy rates (36.8% vs. 45.5%, p = 0.59). The median number of harvested lymph node was 4.0 and 5.0 for LLR and OLR, respectively (p = 0.347). There were no associations between approach and 3-year overall and disease-free survival between LLR and OLR (49.8% vs. 63.2% and 39.6% vs. 21.5%, p = 0.66 and p = 0.69)., Discussion: With appropriate patient selection and when compared to OLRs, LLRs for GBC and iCCA are feasible, safe and offer potential short-term benefits without compromising on oncological resection principals and long-term outcomes., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Perioperative neurocognitive disorders (PNDs) are characterized by confusion, difficulty with executive function, and episodic memory impairment in the hours to months following a surgical procedure. Postoperative cognitive dysfunction (POCD) represents such impairments that last beyond 30 d postsurgery and is associated with increased risk of comorbidities, progression to dementia, and higher mortality. While it is clear that neuroinflammation plays a key role in PND development, what factors underlie shorter self-resolving versus persistent PNDs remains unclear. We have previously shown that postoperative morphine treatment extends POCD from 4 d (without morphine) to at least 8 weeks (with morphine) in aged male rats, and that this effect is likely dependent on the proinflammatory capabilities of morphine via activation of toll-like receptor 4 (TLR4). Here, we extend these findings to show that TLR4 blockade, using the selective TLR4 antagonist lipopolysaccharide from the bacterium Rhodobacter sphaeroides (LPS-RS Ultrapure), ameliorates morphine-induced POCD in aged male rats. Using either a single central preoperative treatment or a 1 week postoperative central treatment regimen, we demonstrate that TLR4 antagonism (1) prevents and reverses the long-term memory impairment associated with surgery and morphine treatment, (2) ameliorates morphine-induced dysregulation of the postsynaptic proteins postsynaptic density 95 and synaptopodin, (3) mitigates reductions in mature BDNF, and (4) prevents decreased activation of the BDNF receptor TrkB (tropomyosin-related kinase B), all at 4 weeks postsurgery. We also reveal that LPS-RS Ultrapure likely exerts its beneficial effects by preventing endogenous danger signal HMGB1 (high-mobility group box 1) from activating TLR4, rather than by blocking continuous activation by morphine or its metabolites. These findings suggest TLR4 as a promising therapeutic target to prevent or treat PNDs. SIGNIFICANCE STATEMENT With humans living longer than ever, it is crucial that we identify mechanisms that contribute to aging-related vulnerability to cognitive impairment. Here, we show that the innate immune receptor toll-like receptor 4 (TLR4) is a key mediator of cognitive dysfunction in aged rodents following surgery and postoperative morphine treatment. Inhibition of TLR4 both prevented and reversed surgery plus morphine-associated memory impairment, dysregulation of synaptic elements, and reduced BDNF signaling. Together, these findings implicate TLR4 in the development of postoperative cognitive dysfunction, providing mechanistic insight and novel therapeutic targets for the treatment of cognitive impairments following immune challenges such as surgery in older individuals., (Copyright © 2023 the authors.)

Introduction: Resection of oligometastatic pancreatic ductal adenocarcinoma (PDAC) has historically been ineffective, however modern systemic chemotherapy has improved survival. Thus, re-evaluating safety and outcomes of surgical resection in selected patients with limited peritoneal metastasis (PM) warrants consideration., Methods: From 2018 to 2021, patients with PDAC and positive cytology or limited PM without extraperitoneal metastasis and who had an objective response to ≥ 6 months of systemic chemotherapy were enrolled. Patients underwent laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin/mitomycin C. If amenable to a complete cytoreduction, patients went on to cytoreduction and HIPEC., Results: Overall, 18 patients were enrolled and received a median of 14 (interquartile range [IQR] 12-17) cycles of chemotherapy; 16 (89%) patients received chemoradiation. Laparoscopic HIPEC was completed in 17 patients, with a median length of stay of 1 day, and no grade III complications or hematological toxicities were observed. All 18 patients subsequently underwent a complete cytoreduction (CC-0) along with definitive treatment of the primary tumor, with formal resection (7/18), irreversible electroporation (IRE; 10/18), or intraoperative radiation therapy (IORT; 1/18). Median PCI was 2 (IQR 0-4), median LOS was 7 days (IQR 6-8), and 7 (39%) patients were readmitted. Eight (44%) patients experienced grade 3 or higher complications, including one 30-day mortality. At a median follow-up of 16 months, the median progression-free survival was 20 months and the median overall survival was 26 months., Conclusion: Cytoreduction and HIPEC for selected patients with low-volume PM from PDAC is safe and feasible with favorable short-term outcomes. A phase II trial (NCT04858009) is now enrolling to further assess this multimodality approach in select patients., (© 2022. Society of Surgical Oncology.)

Background: Perihilar cholangiocarcinoma (PHC) is a rare malignancy that arises at the biliary confluence. Achieving a margin-negative resection (R0) is challenging given the anatomic location of tumors and remains the most important prognostic indicator of long-term survival. The objective of this study is to review the impact of intraoperative revision of positive biliary margins in PHC on oncologic outcomes., Patients and Methods: Electronic databases were searched from inception to October 2021. Studies comparing three types of patients undergoing resection of PHC with intraoperative frozen section of the proximal and/or distal bile ducts were identified: those who were margin-negative (R0), those with an initially positive margin who had revised negative margins (R1R0), and those with a persistently positive margin with or without revision of a positive margin (R1). The primary outcome was overall survival (OS). Secondary outcomes included risk of postoperative complication., Results: A total of 449 studies were screened. Ten retrospective observational studies reporting on 1955 patients were included. Patients undergoing successful revision of a positive proximal and/or distal bile duct margin (R1R0) had similar OS to those with a primary margin-negative resection (R0) [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.72-1.19, p = 0.56, I 2 = 84%], and significantly better OS than patients with a positive final bile duct margin (R1) (HR 0.52, 95% CI 0.34-0.79, p = 0.002, I 2 = 0%). There was no increase in the risk of postoperative complications associated with additional resection, although postoperative morbidity was inconsistently reported., Conclusions: This review supports routine intraoperative biliary margin evaluation during resection of PHC with revision if technically feasible., (© 2022. Society of Surgical Oncology.)

Background: Arterial resection (AR) for pancreatic adenocarcinoma is increasingly considered at specialized centers. We aimed to examine the incidence, risk factors, and outcomes of hepatic artery (HA) occlusion after revascularization., Methods: We included patients undergoing HA resection with interposition graft (IG) or primary end-to-end anastomoses (EE). Complete arterial occlusion (CAO) was defined as "early" (EO) or "late" (LO) before/after 90 days respectively. Kaplan-Meier and change-point analysis for CAO was performed., Results: HA resection was performed in 108 patients, IG in 61% (66/108) and EE in 39% (42/108). An equal proportion (50%) underwent HA resection alone or in combination with celiac and/or superior mesenteric artery. CAO was identified in 18% of patients (19/108) with arterial IG least likely to occlude (p=0.019). Hepatic complications occurred in 42% (45/108) and correlated with CAO, symptomatic patients, venous resection, and postoperative portal venous patency. CAO-related operative mortality was 4.6% and significantly higher in EO vs LO (p = 0.046). Median CAO occlusion was 126 days. With change-point analysis, CAO was minimal beyond postoperative day 158., Conclusion: CAO can occur in up to 18% of patients and the first 5-month post-operative period is critical for surveillance. LO is associated with better outcomes compared to EO unless there is inadequate portal venous inflow., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: Following liver resection (LR) for HCC, the likelihood of survival is dynamic, in that multiple recurrences and/or metastases are possible, each having variable impacts on outcomes. We sought to evaluate the natural progression, pattern, and timing of various disease states after LR for HCC using multistate modeling and to create a practical calculator to provide prognostic information for patients and clinicians., Approach and Results: Adult patients undergoing LR for HCC between January 2000 and December 2018 were retrospectively identified at a single center. Multistate analysis modeled post-LR tumor progression by describing transitions between distinct disease states. In this model, the states included surgery, intrahepatic recurrence (first, second, third, fourth, fifth), distant metastasis with or without intrahepatic recurrence, and death. Of the 486 patients included, 169 (34.8%) remained recurrence-free, 205 (42.2%) developed intrahepatic recurrence, 80 (16.5%) developed distant metastasis, and 32 (7%) died. For an average patient having undergone LR, there was a 33.1% chance of remaining disease-free, a 31.0% chance of at least one intrahepatic recurrence, a 16.3% chance of distant metastasis, and a 19.8% chance of death within the first 60 months post-LR. The transition probability from surgery to first intrahepatic recurrence, without a subsequent state transition, increased from 3% (3 months) to 17.4% (30 months) and 17.2% (60 months). Factors that could modify these probabilities included tumor size, satellite lesions, and microvascular invasion. The online multistate model calculator can be found on https://multistatehcc.shinyapps.io/home/., Conclusions: In contrast to standard single time-to-event estimates, multistate modeling provides more realistic prognostication of outcomes after LR for HCC by taking into account many postoperative disease states and transitions between them. Our multistate modeling calculator can provide meaningful data to guide the management of patients undergoing postoperative surveillance and therapy., (© 2022 American Association for the Study of Liver Diseases.)

Background: While surgical resection has a demonstrated utility for patients with colorectal liver metastases (CRLM), it is unclear whether minimally invasive surgery (MIS) or an open approach should be used. This review sought to assess the efficacy and safety of MIS versus open hepatectomy for isolated, resectable CRLM when performed separately from (Key Question (KQ) 1) or simultaneously with (KQ2) the resection of the primary tumor., Methods: PubMed, Embase, Google Scholar, Cochrane CENTRAL, International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov databases were searched to identify both randomized controlled trials (RCTs) and non-randomized comparative studies published during January 2000-September 2020. Two independent reviewers screened literature for eligibility, extracted data from included studies, and assessed internal validity using the Cochrane Risk of Bias 2.0 Tool and the Newcastle-Ottawa Scale. A random-effects meta-analysis was performed using risk ratios (RR) and mean differences (MD)., Results: From 2304 publications, 35 studies were included for meta-analysis. For staged resections, three RCTs and 20 observational studies were included. Data from RCTs indicated MIS having similar disease-free survival (DFS) at 1-year (RR 1.03, 95%CI 0.70-1.50), overall survival (OS) at 5-years (RR 1.04, 95%CI 0.84-1.28), fewer complications of Clavien-Dindo Grade III (RR 0.62, 95%CI 0.38-1.00), and shorter hospital length of stay (LOS) (MD -6.6 days, 95%CI -10.2, -3.0). For simultaneous resections, 12 observational studies were included. There was no evidence of a difference between MIS and the open group for DFS-1-year, OS-5-year, complications, R0 resections, blood transfusions, along with lower blood loss (MD -177.35 mL, 95%CI -273.17, -81.53) and shorter LOS (MD -3.0 days, 95%CI -3.82, -2.17)., Conclusions: Current evidence regarding the optimal approach for CRLM resection demonstrates similar oncologic outcomes between MIS and open techniques, however MIS hepatectomy had a shorter LOS, lower blood loss and complication rate, for both staged and simultaneous resections., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To identify change management (CM) strategies for implementing novel artificial intelligence and similar novel technologies in operating rooms and create a new CM model for future trials and applications inspired by the abovementioned strategies and established models., Methods: Key phases of technology implementation were defined, and strategies for transformational CM were created and applied in a recent CM experience at our institution between October 15, 2020 and October 15, 2021. We appraised existing CM models and propose the newly created model., Results: The key phases of the technology implementation were as follows: (1) team assembly; (2) committee approvals; (3) CM; and (4) system installation and go-live. Key strategies were (1) assemble team with necessary expertise; (2) anticipate potential institutional cultural and regulatory hurdles; (3) add agility to project planning and execution; (4) accommodate institutional culture and regulations; (5) early clinical partner buy-in and stakeholder engagement; and (6) consistent communication, all of which contributed to the new CM model creation., Conclusion: Key CM strategies and a new CM model addressing the unique needs and characteristics of operating room novel technology implementation were identified and created. The new model may be customized and tested for individual institution and project's needs and characteristics., (© 2022 The Authors.)

Background: Margin-negative (R0) resection is the strongest positive prognostic factor in perihilar cholangiocarcinoma (PHC). Due to its anatomic location, the caudate lobe is frequently involved in PHC. This review aimed to examine the impact of caudate lobe resection (CLR) in addition to hepatectomy and bile duct resection for patients with PHC., Methods: The MEDLINE, EMBASE, and Cochrane databases were systematically reviewed from inception to October 2021 to identify studies comparing patients undergoing surgical resection with hepatectomy and bile duct resection with or without CLR for treatment of PHC. Outcomes included the proportion of patients achieving R0 resection, overall survival (OS), and perioperative morbidity., Results: Altogether, 949 studies were screened. The review included eight observational studies reporting on 1137 patients. The patients who underwent CLR had a higher likelihood of R0 resection (odds ratio [OR], 5.85; 95% confidence interval [CI], 2.64-12.95) and a better OS (hazard ratio [HR], 0.65; 95% CI, 0.54-0.79) than those who did not. The use of CLR did not increase the risk of perioperative morbidity (OR, 1.03; 95% CI, 0.65-1.63)., Conclusions: Given the higher likelihood of R0 resection, improved OS, and no apparent increase in perioperative morbidity, this review supports routine caudate lobectomy in the surgical management of PHC. These results should be interpreted with caution given the lack of high-quality prospective data and the high probability of selection bias., (© 2022. Society of Surgical Oncology.)

Background: Approximately 40-50% of patients with pancreatic neuroendocrine tumors (pNETs) initially present with distant metastases. Little is known about the outcomes of patients undergoing combined pancreatic and hepatic resections for this indication., Methods: Patients who underwent hepatectomy for metastatic pNETs at Mayo Clinic Rochester from 2000 to 2020 were retrospectively reviewed. Major pancreatectomy was defined as pancreaticoduodenectomy or total pancreatectomy, and major hepatectomy as right hepatectomy or trisegmentectomy. Characteristics and outcomes of patients who underwent pancreatectomy with simultaneous hepatectomy were compared with those of patients who underwent isolated hepatectomy (with or without prior history of pancreatectomy)., Results: 205 patients who underwent hepatectomy for metastatic pNETs were identified: 131 underwent pancreatectomy with simultaneous hepatectomy and 74 underwent isolated hepatectomy. Among patients undergoing simultaneous hepatectomy, 89 patients underwent minor pancreatectomy with minor hepatectomy, 11 patients underwent major pancreatectomy with minor hepatectomy, 30 patients underwent minor pancreatectomy with major hepatectomy, and 1 patient underwent major pancreatectomy with major hepatectomy. Patients undergoing simultaneous hepatectomy had more numerous liver lesions (10 or more lesions in 54% vs. 34%, p = 0.008), but the groups were otherwise similar. Rates of any major complications (31% versus 24%, p = 0.43), hepatectomy-specific complications such as bile leak, hemorrhage, and liver failure (0.8-7.6% vs. 1.4-12%, p = 0.30-0.99), and 90-day mortality (1.5% vs. 2.7%, p = 0.62) were similar between the two groups. 5-year overall survival was 64% after combined resections and 65% after isolated hepatectomy (p = 0.93)., Conclusion: For patients with metastatic pNETs, combined pancreatic and hepatic resections can be performed with acceptable morbidity and mortality in selected patients at high-volume institutions., (© 2022. The Author(s).)

Background: The decision to undertake pancreaticoduodenectomy for benign and precancerous lesions has historically relied on outcomes data from operations for cancer. We aimed to describe risks for these specific patients and identify the highest risk groups., Methods: The ACS-NSQIP pancreatic targeted data was queried for pancreaticoduodenectomies for benign and pre-cancerous neoplasms from 2014 to 2018. Baseline characteristics, operative techniques and outcomes were examined. Multivariate regression was performed to identify predictors of major complications., Results: 748 patients underwent pancreaticoduodenectomy for (n = 541,72.3%) IPMN, (n = 87,11.6%) MCN, (n = 78,10.4%) serous cystadenoma, and (n = 42,5.6%) solid pseudopapillary neoplasm. Median LOS was 8 days. Major complications (n = 135,18.0%), non-home discharges (n = 83,11.1%) and readmissions (n = 153,20.5%) occurred frequently. In patients ≥ 80 years of age (n = 37), major complications (n = 11,29.7%) and non-home discharge (n = 9,24.3%) were quite common. 5-item modified frailty index ≥ 0.4 (OR 1.84,95%CI 1.06-3.19,p = 0.030), Male sex (OR 1.729,95%CI 1.152-2.595,p = 0.008), Age ≥ 65 (OR 1.63,95%CI 1.05-2.54,p = 0.29) and African-American race (OR 2.50,95%CI 1.22-5.16,p = 0.013) were independent predictors of major morbidity., Conclusions: Pancreaticoduodenectomies in this setting have high rates of major complications. Morbidity extends beyond the index hospitalization, with frequent readmission and non-home discharge. Patient specific factors, rather than technical or disease factors predicted outcomes. In certain patients, particularly those older than 80, the morbidity of this operation may exceed the cancer prevention benefits., (Copyright © 2022. Published by Elsevier Ltd.)