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Hepatic arterial infusion (HAI) pump chemotherapy is an effective therapy for colorectal liver metastases and intrahepatic cholangiocarcinoma. In the setting of recent reports suggesting favorable outcomes in these diseases with HAI, there has been a surge in interest in this treatment worldwide, prompting the opening of many new HAI programs. While significant technical expertise is required for pump implantation, this alone is insufficient to open a safe and sustainable HAI program, and numerous other factors must be considered prior to the first pump implantation. This expert perspective, established using an anonymous web-based survey of experienced multidisciplinary international HAI providers, details the minimum required personnel, expertise, training, and infrastructure to optimize success and sustainability of a safe and effective new HAI program., Competing Interests: Disclosure: Ryan P. Merkow: Relevant financial activities outside the submitted work (Intera Oncology). Louise C. Connell: Consultancy work (Intera Oncology). Bas Groot Koerkamp: In-kind contribution of pumps for a clinical trial investigating HAI (Tricumed), and support for clinical trials investigating HAI (Intera). Andrea Cercek: Relevant financial activities outside the submitted work (Abbvie, Amgen, Agenus, Daiichi Saynko, Merck, GSK, Pfizer, Regenen, Janssen, and Roche). Pending patents: Neoadjuvant PD-1 blockade for mismatch repair-deficient solid tumors; HAI liver-directed therapy for colorectal liver metastases in patients with DPD deficiency. Blase N. Polite: Speaking and consulting (Natera). Michael J. Cavnar, Ana L. Gleisner, Skye C. Mayo, Sepideh Gholami, Paul J. Karanicolas, Marjolein Y.V. Homs, Paul R. Helft, Reema A. Patel, Hope E. Uronis, Michael D’Angelica, and Michael E. Lidsky have no disclosures to declare that may be relevant to the contents of this article., (© 2025. Society of Surgical Oncology.)

Competing Interests: Disclosure: The authors declare no conflicts of interest.

Background: Hepatic arterial infusion (HAI) is an established treatment for patients with unresectable colorectal liver metastases (uCRLM). Until recently, HAI was only performed at a limited number of centers. We previously reported early outcomes suggesting that implementation of a new HAI program is safe and feasible. Here, we report perioperative and oncologic outcomes from an expanded series of patients with uCRLM treated with HAI., Methods: We analyzed outcomes from consecutive patients with uCRLM who underwent HAI pump (HAIP) placement at Duke University Hospital from 2018 to 2023. Demographics, prior treatment, and perioperative and oncologic outcomes were assessed., Results: Overall, 102 patients underwent HAIP placement for uCRLM; 62% were male and median age was 51 years. Most patients (97%) received a median of 12 (range 0-66) prior chemotherapy cycles. Postoperative HAI-specific complications occurred in 23% of patients, including biliary sclerosis in 6%, and the 90-day mortality rate was 3%. 20% converted to resection, 4% underwent transplant, and 2% achieved complete response at 6 months after floxuridine initiation. Median hepatic and extrahepatic progression-free survival (PFS) was 15.7 months and 11.6 months, respectively. Median overall survival (OS) was 38 months from the time of pump implantation (median follow-up time: 30 months)., Conclusions: HAI for uCRLM is safe, feasible, and effective at a new center, with outcomes that recapitulate those previously reported by established centers. Future analysis of our institutional data, which includes mutation status, primary tumor sidedness, and extent of prior therapy could inform selection and treatment strategies for new HAI programs., Competing Interests: Disclosures: John H. Strickler reports consultant or advisory roles for Abbvie, Agenus, Astellas, AstraZeneca, Bayer, Beigene, Daiichi-Sankyo, Eli Lilly, GSK, Johnson and Johnson, Jazz Pharmaceuticals, Merck, Natera, Pfizer, Roche/Genentech, Regeneron, Sanofi, Taiho, Takeda, and Xilio Therapeutics; stock options for Triumvira Immunologics; and research funding or contracted research for Abbvie, Amgen, AStar D3, Bayer, Beigene, Curegenix, Daiichi-Sankyo, Eli Lilly, Erasca, GSK, Leap Therapeutics, Novartis, Pfizer, Quanta Therapeutics, Revolution Medicines, and Roche/Genentech. Benjamin Wildman-Tobriner reports a consultant role for See-Mode Technologies. Annie Liu, Melissa Lowe, Donna Niedzwiecki, Kristen E. Rhodin, Jeremy Sharib, Terence Z. Wong, Charles Y. Kim, Julie Thacker, Christopher Mantyh, John Migaly, Billy Y. Lan, S. David Hsu, Daniel Nussbaum, Sabino Zani, Hope Uronis, Peter J. Allen, and Michael E. Lidsky have no disclosures to declare that may be relevant to the contents of this study., (© 2024. Society of Surgical Oncology.)

Competing Interests: Disclosures: James Harding has received research support from NCI P30-CA008748, NCI U01 CA238444 04, the Society of Memorial Sloan Kettering Cancer Center, Experimental Therapeutics Center, and Cycle for Survival. J.J.H. has received additional research support from AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, CytomX, Debiopharm, Eli Lilly, Genoscience, Incyte, Kinnate Biopharma, Loxo @ Lilly, Novartis, Polaris, Pfizer, Tvardi, Zymeworks, and Yiviva and consulting fees from Adaptimmune, Astrazenica, Bristol Myers Squibb, Exelexis, Elevar, Eisai, Genoscience (uncompensated), Hepion, Imvax, Merck (DSMB) Medivir, QED, RayzeBio, Servier, Tempus, Tyra, and Zymeworks (uncompensated). Jeffrey Drebin declares Equity shares of ALNY and IONS purchased via a brokerage account. Andrea Cercek receives advisory fees from Abbvie, Amgen, Agents, Daiichi Snayko, GSK, Merck, Janssen, Pfizer/Seagen, Regeneron, and Roche and research funding from GSK and Pfizer/Seagen. Eileen O'Reilly received research funding to institution from Genentech/Roche, BioNTech, AstraZeneca, Arcus, Elicio, Parker Institute, NIH/NCI, Digestive Care, Break Through Cancer, and Agenus; consulting fees/DSMB from Arcus, AstraZeneca, Ability Pharma, Alligator BioSciences, Agenus, BioNTech, Ipsen, Merck, Moma Therapeutics, Novartis, Syros, Leap Therapeutics, Astellas, BMS, Fibrogen, Revolution Medicines, Regeneron, Merus, and Tango and from Abbvie (spouse); and other support from American Association of Cancer Research, American Society of Clinical Oncology, Imedex, Research To Practice, SU2C. Alice Wei received consulting fees from Histosonics (DSMB member) and clinical trial funding from Ipsen. John Strickler has a consultant or advisory role with Abbvie, Amgen, Astellas, AstraZeneca, Bayer, Beigene, BMS, Daiichi-Sankyo, Eli Lilly, GE Healthcare, GSK, Ipsen, Johnson and Johnson, Jazz Pharmaceuticals, Merck, Natera, Pfizer, Roche/Genentech, Regeneron, Sanofi, Taiho, Takeda, and Xilio Therapeutics; stock options from Triumvira Immunologics; and research funding or contracted research from Abbvie, Amgen, Apollo Therapeutics, AStar D3, Bayer, Beigene, Curegenix, Daiichi-Sankyo, Eli Lilly, Erasca, GSK, Leap Therapeutics, Novartis, Pfizer, Quanta Therapeutics, Revolution Medicines, and Roche/ Genentech.

Background: A growing number of centers offer hepatic artery infusion pump (HAIP) chemotherapy for advanced liver malignancies. While small series have demonstrated feasibility of robotic HAIP placement, comparison of outcomes with open placement is lacking. We compared outcomes after robotic versus open HAIP placement., Methods: We retrospectively reviewed HAIP placement without concurrent hepatectomy at Memorial Sloan Kettering Cancer Center from 1 January 2011 to 15 September 2022, and Duke Health from 1 November 2018 to 18 May 2023. Patients with prior liver surgery or who required catheterization of a non-standard vessel were excluded. Propensity score matching weights (PSMW) were calculated using age, sex, race, body mass index, American Society of Anesthesiologists class, neoadjuvant chemotherapy, colorectal procedure, and institution. Survey-weighted generalized linear models assessed the relationship between approach and outcomes., Results: Of 2002 consecutive HAIP placements, 819 (645 open/174 robotic) met the inclusion criteria. A higher proportion of open procedures involved combined colorectal procedures; other patient characteristics were similar. Overall, 15% of patients experienced an HAIP-specific complication and 12% required re-intervention; 2.7% had HAIP failure ≤ 90 days. After PSMW, the robotic approach had a longer operative time (β = 68 min, 95% confidence interval [CI] 55-81, p < 0.001) but shorter length of stay (β = - 1.8 days, 95% CI - 2.3 to 1.3, p < 0.001). The robotic approach was associated with increased HAIP-specific complications (odds ratio [OR] 1.72, p = 0.025) and re-intervention (OR 2.33, p < 0.001), with no difference in time to initiation of HAIP chemotherapy or HAIP failure., Conclusions: Robotic HAIP placement was associated with increased postoperative complications and significantly shorter length of stay, with similar time to initiation of HAIP therapy. There was no difference in the rate of early HAIP failure versus the open approach. These results suggest robotic HAIP placement is feasible and effective., Competing Interests: Disclosures: Alice C. Wei reports receiving consulting fees from Histosonics and institutional clinical trial funding from Ipsen. Sabino Zani reports consulting for Asensus Surgical. Jeffrey Drebin reports equity shares in ALNY, IONS and ARWR, purchased from a broker. Lauren E. Schleimer, Annie Liu, Hannah L. Kalvin, Ahmad Bashir Barekzai, Ankur P. Choubey, Joslyn Jung, Rubiya Haque, William R. Jarnagin, Vinod P. Balachandran, Ruben Geevarghese, Brett Marinelli, Mithat Gonen, Peter J. Allen, Michael I. D’Angelica, T. Peter Kingham, Michael E. Lidsky, and Kevin C. Soares have no conflicts of interest disclosures to report that may be relevant to the contents of this study., (© 2025. The Author(s).)

Background: Randomized data suggest improved survival with adjuvant chemotherapy for biliary tract cancers; however, subset analyses of intrahepatic cholangiocarcinoma (IHC) show limited survival benefit. This study evaluated the impact of adjuvant chemotherapy on recurrence patterns and overall survival (OS) in patients with resected IHC., Methods: Patients who underwent curative-intent resection for IHC were identified within a bi-institutional dataset and the National Cancer Database (NCDB). Patients were stratified by receipt of adjuvant chemotherapy. Site of first recurrence was categorized as liver only, regional, distant, or multifocal. Survival outcomes within each dataset were compared using Kaplan-Meier methods., Results: In the bi-institutional dataset, 347 patients underwent resection for IHC, and 149 (43%) patients received adjuvant cytotoxic chemotherapy. Recurrence was observed in 222 (64.0%) patients. OS was similar between groups (adjuvant vs. observation: 42 vs. 49 months; p = 0.13), and did not differ in patients who received capecitabine specifically (p = 0.09) or in a risk-adjusted multivariable analysis. Recurrence-free survival was worse in those who received adjuvant chemotherapy (p = 0.04), although the liver was the most common site of recurrence in both groups (0.63). A similar analysis of 1159 resected IHCs from the NCDB also demonstrated no association between adjuvant chemotherapy and OS (49 vs. 57 months; p = 0.1)., Conclusion: Adjuvant chemotherapy may not be associated with improved OS in IHC and did not have an impact on hepatic recurrence in this retrospective analysis. Future investigation to identify more effective adjuvant systemic regimens and/or explore the potential role of adjuvant liver-directed therapies to reduce hepatic recurrence that may improve OS for IHC is warranted., Competing Interests: Disclosures: James J. Harding has received research support from NCI P30-CA008748, NCI U01 CA238444 04, the Society of Memorial Sloan Kettering Cancer Center, Experimental Therapeutics Center, and Cycle for Survival; received additional research support from AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, CytomX, Debiopharm, Eli Lilly, Genoscience, Incyte, Kinnate Biopharma, Loxo @ Lilly, Novartis, Polaris, Pfizer, Tvardi, Zymeworks, and Yiviva; and received consulting fees from Adaptimmune, AstraZeneca, Bristol Myers Squibb, Exelexis, Elevar, Eisai, Genoscience (uncompensated), Hepion, Imvax, Merck (DSMB) Medivir, QED, RayzeBio, Servier, Tempus, Tyra, and Zymeworks (uncompensated). Jeffrey Drebin declares equity shares of ALNY and IONS purchased via a brokerage account. Andrea Cercek has participated in Advisory Boards for Abbvie, Amgen, Agents, Daiichi Snayko, GSK, Merck, Janssen, Pfizer/Seagen, Regeneron, and Roche, and has received research funding from GSK and Pfizer/Seagen. Eileen O'Reilly has received research funding (paid to her institution) from Genentech/Roche, BioNTech, AstraZeneca, Arcus, Elicio, Parker Institute, NIH/NCI, Digestive Care, Break Through Cancer, and Agenus; undertaken consulting work and is a member of the Data Safety Monitoring Board for Arcus, AstraZeneca, Ability Pharma, Alligator BioSciences, Agenus, BioNTech, Ipsen, Merck, Moma Therapeutics, Novartis, Syros, Leap Therapeutics, Astellas, BMS, Fibrogen, Revolution Medicines, Regeneron, Merus, and Tango; Abbvie (spouse); and ‘other’ disclosures pertaining to the American Association of Cancer Research, American Society of Clinical Oncology, Imedex, Research To Practice, and SU2C. Alice Wei has undertaken consulting work and is a member of the Data Safety Monitoring Board for Histosonics, and has received clinical trial funding from Ipsen. John Strickler has participated in consultancy or advisory roles for Abbvie, Amgen, Astellas, AstraZeneca, Bayer, Beigene, BMS, Daiichi-Sankyo, Eli Lilly, GE Healthcare, GSK, Ipsen, Johnson and Johnson, Jazz Pharmaceuticals, Merck, Natera, Pfizer, Roche/Genentech, Regeneron, Sanofi, Taiho, Takeda, and Xilio Therapeutics; has stock options in Triumvira Immunologics; and has received research funding from or undertaken contracted research for Abbvie, Amgen, Apollo Therapeutics, AStar D3, Bayer, Beigene, Curegenix, Daiichi-Sankyo, Eli Lilly, Erasca, GSK, Leap Therapeutics, Novartis, Pfizer, Quanta Therapeutics, Revolution Medicines, and Roche/Genentech. Jeremy Sharib, Kristen E. Rhodin, Annie Liu, Sarah McIntyre, Alex Bartholomew, Sabran Masoud, Isabel DeLaura, Nancy E. Kemeny, Ghassan K. Abou-Alfa, Diane Reidy-Lagunes, Louise Catherine Connell, Imane El Dika, Vinod P. Balachandran, Kevin C. Soares, T. Peter Kingham, Michael I. D’Angelica, Hope Uronis, S. David Hsu, Michael Morse, Sabino Zani, Peter J. Allen, William R. Jarnagin, and Michael E. Lidsky have no conflicts of interest to declare that may be relevant to the contents of this study., (© 2025. Society of Surgical Oncology.)

Competing Interests: Disclosures: John H. Strickler reports a consultant or advisory role for Abbvie, Agenus, Astellas, AstraZeneca, Bayer, Beigene, Daiichi-Sankyo, Eli Lilly, GSK, Johnson and Johnson, Jazz Pharmaceuticals, Merck, Natera, Pfizer, Roche/Genentech, Regeneron, Sanofi, Taiho, Takeda, and Xilio Therapeutics; holds stock options in Triumvira Immunologics; and has received research funding from or contracted research for Abbvie, Amgen, AStar D3, Bayer, Beigene, Curegenix, Daiichi-Sankyo, Eli Lilly, Erasca, GSK, Leap Therapeutics, Novartis, Pfizer, Quanta Therapeutics, Revolution Medicines, and Roche/ Genentech. Benjamin Wildman-Tobriner is a consultant for See-Mode Technologies. Annie Liu, Melissa Lowe, Donna Niedzwiecki, Kristen E. Rhodin, Jeremy Sharib, Terence Z. Wong, Charles Y. Kim, Julie Thacker, Christopher Mantyh, John Migaly, Billy Y. Lan, S. David Hsu, Daniel Nussbaum, Sabino Zani, Hope Uronis, Peter J. Allen, and Michael E. Lidsky have no disclosures to declare that may be relevant to the contents of this study.

Importance: Ampullary adenocarcinoma (AA) is characterized by clinical and genomic heterogeneity. A previously developed genomic classifier defined biologically distinct phenotypes with greater accuracy than standard histologic classification. External validation is needed before routine clinical use., Objective: To test external validity of the prognostic value of the hidden genome classifier of AA., Design, Setting, and Participants: This retrospective cohort study took place at 6 international academic institutions. Consecutive patients (n = 192) who underwent curative-intent resection of histologically confirmed AA were included. The data were analyzed from January 2005 through July 2020., Exposures: The multilevel meta-feature regression model previously trained on a prospectively sequenced cohort of 3411 patients (1001 pancreatic adenocarcinoma, 165 distal bile duct adenocarcinoma, and 2245 colorectal adenocarcinoma) was applied to AA sequencing data to quantify the relative proportions of parental cell of origin., Main Outcome and Measures: Genomic classification was correlated with immunohistologic subtype (intestinal [INT] or pancreatobiliary [PB]) and with overall survival (OS), using the log-rank test and Cox proportional hazard models., Results: Among 192 patients with AA (median age, 69.0 [IQR, 60.0-74.0] years and 134 were male [64%]), concordance between immunohistologic and genomic subtypes was 55%. Most INT subtype tumors were categorized into the colorectal genomic subtype (43 of 57 [72.9%]). Of the 114 PB subtype tumors, 29 had a pancreatic genomic profile (25.4%) and 24 had a distal bile duct genomic profile (21.1%). Whereas the standard immunohistologic subtypes were not associated with survival (log rank P = .26), predicted genomic probabilities were correlated with survival probability. Genomic scores with higher colorectal probability were associated with higher survival probability; higher pancreatic and distal bile duct probabilities were associated with lower survival probability., Conclusions and Relevance: The AA genomic classifier is reproducible with available molecular testing in a diverse international cohort of patients and improves stratification of the divergent clinical outcomes beyond standard immunohistologic classification. These data provide a molecular classification that may be incorporated into clinical trials for prospective validation.

Background: Pancreatic acinar cell carcinoma (pACC) is a rare neoplasm of the exocrine pancreas. There is a dearth of information about tumor characteristics and patient outcomes. This study describes the clinical characteristics, genetic alterations, and survival outcomes of resected pACC., Patients and Methods: Consecutive patients undergoing pancreatectomy for pathologically confirmed pACC from 1999 to 2022 across three high-volume pancreas surgery centers were analyzed. Patient demographics, tumor characteristics, treatment data, and genetic sequencing were obtained through retrospective abstraction., Results: A total of 61 patients with resected pACC were identified. Median overall survival (OS) was 73 months and median recurrence free survival was 22 months. Nine patients underwent resection for oligometastatic disease; median OS was not reached after a median follow-up of 31 months from date of metastasectomy. Adjuvant chemotherapy was administered in 67% of patients with FOLFOX/FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin, ± irinotecan) the most common regimen (58%). Sequencing data were obtained in 47 (77%) patients. A mutation in at least one of three core genes associated with the homologous recombination repair (HRR) pathway (BRCA1, BRCA2, or PALB2) occurred in 26% (n = 12) with BRCA2 the most frequently identified. A mutation in any other "non-core" gene associated with DNA damage repair or the HRR pathway was identified in 45% (n = 21) with a high tumor mutational burden of > 10 mutations per megabase in 13%., Conclusions: Resection of pACC is associated with favorable survival outcomes, even in the setting of oligometastatic disease. Mutations in the HRR pathway are common, providing opportunities for potential targeted therapeutic options., (© 2024. The Author(s).)

Background: The Centers for Medicare and Medicaid Services (CMS) price transparency rule tries to facilitate cost-conscious decision-making. For surgical services, such as pancreaticoduodenectomy (PD), factors mediating transparency and real-world reimbursement are not well described., Methods: The Leapfrog Survey was used to identify United States hospitals performing PD. Financial and operational data were obtained from Turquoise Health and CMS Cost Reports. Chi-square tests and modified Poisson regression evaluated associations with reimbursement disclosure. Two-part logistic and gamma regression models estimated effects of hospital factors on commercial, Medicare, and self-pay reimbursements for PD., Results: Of 452 Leapfrog hospitals, 295 (65%) disclosed PD hospital or procedure reimbursements. Disclosing hospitals were larger (beds > 200: 81.0% vs. 71.3%, p = 0.04), reported higher net margins (0.7% vs. - 2.1%, p = 0.04), more likely for-profit (26.1% vs. 6.4%, p < 0.001), and teaching-affiliated (82.0% vs. 65.6%, p < 0.001). Nonprofit status conferred hospitalization reimbursement increases of $8683-$12,329, while moderate market concentration predicted savings up to $5066. Teaching affiliation conferred reimbursement increases of $4589-$16,393 for hospitalizations and $644 for procedures. Top Leapfrog volume ratings predicted an increase of up to $7795 for only Medicare hospitalization reimbursement., Conclusions: Nondisclosure of hospital and procedural reimbursements for PD remains a major issue. Transparency was noted in hospitals with higher margins, size, and academic affiliation. Factors associated with higher reimbursement were non-profit status, academic affiliation, and more equitable market share. Reimbursement inconsistently tracked with PD quality or volume measures. Policy changes may be required to incentivize reimbursement disclosure and translate transparency into increased value for patients., (© 2024. Society of Surgical Oncology.)

Introduction: Desmoid tumors (DTs) are rare, fibroblastic cell proliferations that can exhibit locally aggressive behavior but lack metastatic potential. Initial management has traditionally involved upfront resection; however, contemporary guidelines and expert panels have increasingly advocated for prioritizing active surveillance strategies., Methods: A single-institution, retrospective chart review identified all patients diagnosed with a primary DT at any site from 2007 to 2020. The primary outcome was the initial management strategy over time. Secondary outcomes included treatment-free survival (TFS) and time to treatment (TTT) for those undergoing active surveillance, as well as recurrence-free survival (RFS) and time to recurrence for those undergoing resection., Results: Overall, 103 patients were included, with 68% female and a median follow-up of 44 months [24-74]. The most common tumor locations included the abdominal wall (27%), intra-abdominal/mesenteric (25%), chest wall (19%), and extremity (10%). Initial management included resection (60%), systemic therapy (20%), active surveillance (18%), and cryoablation (2%). Rates of surgical resection significantly decreased (p < 0.001) over time, from 69.6% prior to 2018 to 29.2% after 2018. For those treated with upfront resection, 5-year RFS was 41.2%, and for patients undergoing initial active surveillance, TFS was 66.7% at 2 years, with a median TTT of 4 months [4-10]., Conclusions: This single-institution cohort at a tertiary medical center spanning over a decade demonstrates the transition to active surveillance for initial management of DTs, and highlights salient metrics in the era of surveillance. This trend mirrors recommended treatment strategies by expert panels and consensus guidelines., (© 2024. Society of Surgical Oncology.)

Background: Early-onset colorectal cancer with synchronous liver metastasis (EO-CRLM) is a growing concern with a grim prognosis., Methods: EO-CRLM patients were identified from the National Cancer Database. Random survival forest model and random forest (RF) model were developed for the prediction of overall survival (OS) and 6-month mortality, respectively., Results: The variables with top contributions for random survival forest model of OS included primary tumor resection, chemotherapy and bone metastases. The AUCs of 1-, 3- and 5-year OS were 0.787, 0.763 and 0.761, respectively. The individualized risk profile predicted by the models closely aligned with the actual survival outcomes observed for the patients. The variables with top contributions for RF model for 6-month mortality included chemotherapy, Charlson-Deyo comorbidity score and presence of tumor deposits. RF model for 6-month mortality resulted in an AUC of 0.821 in training set, 0.828 in cross-validation and 0.852 in testing cohort. RF models for OS and 6-month mortality exhibited great net benefit with favorable clinical utility., Conclusion: The models generated in this study accurately identified EO-CRLM patients at risk of worse OS and short-term mortality, which may complement standard clinical assessment and aid in creation of advanced care planning., Competing Interests: Conflicts of interest None to declare.., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. All rights reserved.)

Background: Liver transplantation (LT) has been shown to be superior to resection in highly selected patients with perihilar cholangiocarcinoma (CCA), yet has traditionally been contraindicated for intrahepatic CCA (iCCA). Herein, we aimed to examine contemporary trends and outcomes for surgical resection and LT for iCCA., Methods: The National Cancer Database was queried for patients presenting with stage I-III iCCA between 2010 and 2018 who underwent resection or LT. Overall survival (OS) was compared with Kaplan-Meier and multivariable Cox proportional hazards methods stratified by management. Secondary analysis of patients undergoing transplant for CCA was performed with the United Network for Organ Sharing database., Results: Of 2565 patients, 2412 (94.0%) underwent resection and 153 (5.96%) LT of whom 84 (54.9%) received neoadjuvant therapy. Utilization of LT remained between 3.9% and 7.8% annually. Unadjusted 5-year OS was higher for LT than resection (59.8% vs 39.9%, P = .0067), yet adjusted analysis revealed no significant difference in mortality (hazard ratio, 0.91; 95% CI, 0.66-1.27; P = .58). On secondary analysis including 437 patients with all subtypes of CCA, unadjusted 5-year OS was higher for non-CCA indications (79% vs 52%-54%, P < .001)., Conclusion: Utilization of LT for iCCA remains low and many cases are likely incidental. Although partial hepatectomy remains the standard of care for patients with resectable disease, our findings suggest that highly selected patients with unresectable iCCA may achieve favorable outcomes after LT. Granular, prospective data are needed to identify patients most likely to benefit from transplant and allocate scarce liver grafts., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Background: Radical cholecystectomy is recommended for T1B and greater gallbladder cancer, however, there are conflicting reports on the utility of extended resection for T1B disease. Herein, we characterize outcomes following simple and radical cholecystectomy for pathologic stage T1B gallbladder cancer., Methods: The National Cancer Database (NCDB) was queried for patients with pathologic T1B gallbladder cancer diagnosed from 2004 to 2018. Patients were stratified by surgical management. Overall survival (OS) was compared with Kaplan-Meier and multivariable Cox proportional hazards methods., Results: Altogether, 950 patients were identified with pathologic T1B gallbladder cancer: 187 (19.7 %) receiving simple and 763 (80.3 %) radical cholecystectomy. Median OS was 89.5 (95 % CI 62.5-137) and 91.4 (95 % CI 75.9-112) months for simple and radical cholecystectomy, respectively (log-rank p = 0.55). Receipt of simple cholecystectomy was not associated with greater hazard of mortality compared to radical cholecystectomy (HR 1.23, 95 % CI 0.95-1.59, p = 0.12)., Discussion: In this analysis, we report comparable outcomes with simple cholecystectomy among patients with pathologic T1B gallbladder cancer. These findings suggest that highly selected patients, such as those with R0 resection and imaging at low risk for residual disease and/or nodal metastasis, may not benefit from extended resection; however, radical cholecystectomy remains standard of care until prospective validation can be achieved., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Robotic pancreaticoduodenectomy (RPD) has a learning curve of approximately 30-250 cases to reach proficiency. The learning curve for laparoscopic pancreaticoduodenectomy (LPD) at Duke University was previously defined as 50 cases. This study describes the RPD learning curve for a single surgeon following experience with LPD. LPD and RPD were retrospectively analyzed. Continuous pathologic and perioperative metrics were compared and learning curve were defined with respect to operative time using CUSUM analysis. Seventeen LPD and 69 RPD were analyzed LPD had an inverted learning curve possibly accounting for proficiency attained during the surgeon's fellowship and acquisition of new skills coinciding with more complex patient selection. The learning curve for RPD had three phases: accelerated early experience (cases 1-10), skill consolidation (cases 11-40), and improvement (cases 41-69), marked by reduction in operative time. Compared to LPD, RPD had shorter operative time (379 vs 479 min, p < 0.005), less EBL (250 vs 500, p < 0.02), and similar R0 resection. RPD also had improved LOS (7 vs 10 days, p < 0.007), and lower rates of surgical site infection (10% vs 47%, p < 0.002), DGE (19% vs 47%, p < 0.03), and readmission (13% vs 41%, p < 0.02). Experience in LPD may shorten the learning curve for RPD. The gap in surgical quality and perioperative outcomes between LPD and RPD will likely widen as exposure to robotics in General Surgery, Hepatopancreaticobiliary, and Surgical Oncology training programs increase., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Competing Interests: The authors declare no conflicts of interest.

Purpose: Intrahepatic cholangiocarcinoma (ICCA) is characterized by significant phenotypic and clinical heterogeneities and poor response to systemic therapy, potentially related to underlying heterogeneity in oncogenic alterations. We aimed to characterize the genomic heterogeneity between primary tumors and advanced disease in patients with ICCA., Methods: Biopsy-proven CCA specimens (primary tumor and paired advanced disease [metastatic disease, progressive disease on systemic therapy, or postoperative recurrence]) from two institutions were subjected to targeted next-generation sequencing. Overall concordance (oncogenic driver mutations, copy number alterations, and fusion events) and mutational concordance (only oncogenic mutations) were compared across paired samples. A subgroup analysis was performed on the basis of exposure to systemic therapy. Patients with extrahepatic CCA (ECCA) were included as a comparison group., Results: Sample pairs from 65 patients with ICCA (n = 54) and ECCA (n = 11) were analyzed. The median time between sample collection was 19.6 months (range, 2.7-122.9). For the entire cohort, the overall oncogenic concordance was 49% and the mutational concordance was 62% between primary and advanced disease samples. Subgroup analyses of ICCA and ECCA revealed overall/mutational concordance rates of 47%/58% and 60%/84%, respectively. Oncogenic concordance was similarly low for pairs exposed to systemic therapy between sample collections (n = 50, 53% overall, 68% mutational). In patients treated with targeted therapy for IDH1/2 alterations (n = 6) or FGFR2 fusions (n = 3), there was 100% concordance between the primary and advanced disease specimens. In two patients, FGFR2 (n = 1) and IDH1 (n = 1) alterations were detected de novo in the advanced disease specimens., Conclusion: The results reflect a high degree of heterogeneity in ICCA and argue for reassessment of the dominant driver mutations with change in disease status.

Background: Despite recommendations for primary tumor resection (PTR) with or without liver resection (LR) in the patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and isolated liver metastases, there are conflicting data for their impact on overall survival (OS)., Methods: 2320 patients with GEP-NETs and isolated liver metastases were identified from NCDB. Multiple imputations were used to accommodate missing data, and inverse probability of treatment weighting (IPTW) was conducted to minimize bias., Results: Patients with PTR had a greater OS than those without PTR (3-year rate of 88.6% vs. 69.9%, P < 0.001), which was preserved in the adjusted analysis (IPTW-adjusted HR = 0.387, 95% CI: 0.264-0.567; P < 0.001). Patients with LR had a greater OS than those without LR (3-year rate 87.7% vs. 75.2%, P = 0.003), which was also preserved in adjusted analysis (IPTW-adjusted HR = 0.450, 95% CI: 0.229-0.885; P = 0.021). Patients undergoing both PTR and LR had the greatest survival advantage than those with other surgical interventions (P < 0.001)., Conclusions: Either PTR or LR is associated with improved survival for GEP-NET patients with isolated liver metastases. However, there remains significant selection bias in the current study, and caution should be exercised when selecting patients for resection., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Objectives: We performed a retrospective analysis within a national cancer registry on outcomes following resection or ablation for intrahepatic cholangiocarcinoma (iCCA)., Methods: The National Cancer Database was queried for patients with clinical stage I-III iCCA diagnosed during 2010-2018, who underwent resection or ablation. Overall survival (OS) was compared with Kaplan-Meier and multivariable Cox proportional hazards methods., Results: Of 2140 patients, 1877 (87.7%) underwent resection and 263 (12.3%) underwent ablation, with median tumor sizes of 5.5 and 3 cm, respectively. Overall, resection was associated with greater median OS (41.2 months (95% confidence interval [95% CI]: 37.6-46.2) vs. 28 months (95% CI: 15.9-28.6) on univariable analysis (p < 0.0001). There was no significant difference on multivariable analysis (p = 0.42); however, there was a significant interaction between tumor size and management. On subgroup analysis of patients with tumors <3 cm, there was no difference in OS between resection versus ablation. However, ablation was associated with increased mortality for tumors ≥3 cm., Conclusion: Although resection is associated with improved OS for tumors ≥3 cm, we observed no difference in survival between management strategies for tumors < 3 cm. Ablation may be an alternative therapeutic strategy for small iCCA, particularly in patients at risk for high surgical morbidity., (© 2023 Wiley Periodicals LLC.)

Background: An increasing number of hepatic artery infusion (HAI) programs have been established worldwide. Practice patterns for this complex therapy across these programs have not been reported. This survey aimed to identify current practice patterns in HAI therapy with the long-term goal of defining best practices and performing prospective studies., Methods: Using SurveyMonkey TM , a 28-question survey assessing current practices in HAI was developed by 12 HAI Consortium Research Network (HCRN) surgical oncologists. Content analysis was used to code textual responses, and the frequency of categories was calculated. Scores for rank-order questions were generated by calculating average ranking for each answer choice., Results: Thirty-six (72%) HCRN members responded to the survey. The most common intended initial indications for HAI at new programs were unresectable colorectal liver metastases (uCRLM; 100%) and unresectable intrahepatic cholangiocarcinoma (uIHC; 56%). Practice patterns evolved such that uCRLM (94%) and adjuvant therapy for CRLM (adjCRLM; 72%) have become the most common current indications for HAI at established centers. Referral patterns for pump placement differed between uCRLM and uIHC, with most patients referred while receiving second- and first-line therapy, respectively, with physicians preferring to evaluate patients for HAI while receiving first-line therapy for CRLM. Concern for extrahepatic disease was ranked as the most important factor when considering a patient for HAI., Conclusions: Indication and patient selection factors for HAI therapy are relatively uniform across most HCRN centers. The increasing use of adjuvant HAI therapy and overall consistency of practice patterns among HCRN centers provides a robust environment for prospective data collection and randomized clinical trials., (© 2023. Society of Surgical Oncology.)

Background: Society guidelines remain inconsistent on the role of endoscopic and radiographic surveillance as an alternative to surgical resection of small gastric gastrointestinal stromal tumors (GISTs). Herein, we aimed to assess survival among patients with gastric GISTs undergoing observation versus surgical resection, stratified by tumor size., Methods: The National Cancer Database (NCDB) was queried for gastric GISTs < 2 cm diagnosed from 2010-2017. Patients were stratified by management strategy-observation vs surgical resection. The primary outcome, overall survival (OS), was examined with Kaplan-Meier and multivariable Cox proportional hazard methods. Subgroup analyses were conducted on tumors < 1 cm and 1-2 cm in size., Results: Altogether, 1208 patients were identified: 439 (36.3%) undergoing observation and 769 (63.7%) receiving surgical resection. In the overall cohort, patients undergoing surgical resection demonstrated improved survival (93.6 vs. 88.8% 5-year OS, p=0.02). In multivariable analysis, upfront surgical resection was not associated with a reduction in mortality; however, there was a significant interaction with tumor size. For patients with tumors < 1 cm, there was no difference in survival based on management strategy. However, resection of tumors 1-2 cm was associated with improved survival relative to surveillance., Conclusions: While surgical resection and surveillance were associated with similar survival for patients with gastric GISTs < 1 cm, this NCDB analysis suggests that patients with tumor size ≥ 1 cm may benefit from upfront surgical resection. Prospective studies comparing these two approaches and their impact on recurrence-free and disease-specific survival are needed to better align consensus guidelines and recommendations., (© 2023. The Society for Surgery of the Alimentary Tract.)

Background: Hepatectomy is the cornerstone of curative-intent treatment for intrahepatic cholangiocarcinoma (ICC). However, in patients unable to be resected, data comparing efficacy of alternatives including thermal ablation and radiation therapy (RT) remain limited. Herein, we compared survival between resection and other liver-directed therapies for small ICC within a national cancer registry., Patients and Methods: Patients with clinical stage I-III ICC < 3 cm diagnosed 2010-2018 who underwent resection, ablation, or RT were identified in the National Cancer Database. Overall survival (OS) was compared using Kaplan-Meier and multivariable Cox proportional hazards methods., Results: Of 545 patients, 297 (54.5%) underwent resection, 114 (20.9%) ablation, and 134 (24.6%) RT. Median OS was similar between resection and ablation [50.5 months, 95% confidence interval (CI) 37.5-73.9; 39.5 months, 95% CI 28.7-58.4, p = 0.14], both exceeding that of RT (20.9 months, 95% CI 14.1-28.3). RT patients had high rates of stage III disease (10.4% RT vs. 1.8% ablation vs. 11.8% resection, p < 0.001), but the lowest rates of chemotherapy utilization (9.0% RT vs. 15.8% ablation vs. 38.7% resection, p < 0.001). In multivariable analysis, resection and ablation were associated with reduced mortality compared with RT [hazard ratio (HR) 0.44, 95% CI 0.33-0.58 and HR 0.53, 95% CI 0.38-0.75, p < 0.001, respectively]., Conclusion: Resection and ablation were associated with improved survival in patients with ICC < 3 cm compared with RT. Acknowledging confounders, anatomic constraints of ablation, limitations of available data, and need for prospective study, these results favor ablation in small ICC where resection is not feasible., (© 2023. Society of Surgical Oncology.)

Background: Literature is lacking on the impact of advancements in minimally invasive surgery (MIS) on outcomes for patients with gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs). Herein, we compared perioperative and oncologic outcomes among patients with GEP-NECs undergoing open, laparoscopic, and robotic resection., Methods: Patients with GEP-NECs diagnosed 2010-2019 were identified from the National Cancer Database (NCDB). We used the inverse probability of treatment weighting method to account for selection bias. Patients were stratified by surgical approach; and pairwise comparisons were conducted by analyzing short- and long-term outcomes., Results: Receipt of MIS increased from 34.2% in 2010 to 67.5 % in 2019. Altogether, 6560 patients met study criteria: 3444 (52.5%) underwent open resection, 2783 (42.4%) underwent laparoscopic resection and 333 (5.1%) underwent robotic resection. Compared with open resection, laparoscopic or robotic resection were associated with shorter post-operative length of stay, reduced 30-day and 90-day post-operative mortality, and prolonged overall survival (OS). Compared with laparoscopic resection, robotic resection was associated with reduced 90-day post-operative mortality, however, there was no significant difference in OS., Conclusion: This NCDB analysis demonstrates that MIS approaches for treating GEP-NECs have become more common, with improved perioperative mortality, shorter post-operative length of stay and favorable OS, compared with open resection., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Resection remains the cornerstone of curative-intent treatment for biliary tract cancers (BTCs). However, recent randomized data also support a role for adjuvant chemotherapy (AC). This study aimed to characterize trends in the use of AC and subsequent outcomes in gallbladder cancer and cholangiocarcinoma (CCA)., Methods: The National Cancer Database (NCDB) was queried for patients with resected, localized BTC from 2010 to 2018. Trends in AC were compared among BTC subtypes and stages of disease. Multivariable logistic regression was used to identify factors associated with receipt of AC. Survival analysis was performed with Kaplan-Meier and multivariable Cox proportional hazards methods., Results: The study identified 7039 patients: 4657 (66%) with gallbladder cancer, 1159 (17%) with intrahepatic CCA (iCCA), and 1223 (17%) with extrahepatic CCA (eCCA). Adjuvant chemotherapy was administered to 2172 (31%) patients, increasing from 23% in 2010 to 41% in 2018. Factors associated with AC included female sex, year of diagnosis, private insurance, care at an academic center, higher education, eCCA (vs iCCA), positive margins, and stage II or III disease (vs stage I). Alternatively, increasing age, higher comorbidity score, gallbladder cancer (vs iCCA), and farther travel distance for treatment were associated with reduced odds of AC. Overall, AC was not associated with a survival advantage. However, subgroup analysis showed that AC was associated with a significant reduction in mortality among patients with eCCA., Conclusions: Among the patients with resected BTC, those who received AC were in the minority. In the context of recent randomized data and evolving recommendations, emphasis on guideline concordance with a focus on at-risk populations may improve outcomes., (© 2023. Society of Surgical Oncology.)

Patients with unresectable colorectal liver metastases are commonly treated with systemic chemotherapy to convert their disease to an operable state. Unfortunately, many patients remain unresectable after first-line chemotherapy and resort to second- and third-line regimens with poor results. Liver-directed strategies have historically been used in this setting. There has been a renewed interest in offering hepatic artery infusion chemotherapy combined with systemic chemotherapy to improve resectability or palliate disease. Prospective studies over the past 2 decades have produced encouraging data, even in chemorefractory patients. This therapy has expanded to multiple centers across North America and worldwide with similar results. This review addresses these data, specifically focusing on conversion to resection and palliation of colorectal liver metastases after patients have received multiple lines of systemic chemotherapy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The role of primary tumor resection (PTR) in the survival of gastrointestinal neuroendocrine carcinoma (GI-NEC) patients with liver metastases only remains poorly defined. Therefore, we investigated the impact of PTR on the survival of GI-NEC patients with nonresected liver metastases., Methods: GI-NEC patients with a liver-confined metastatic disease diagnosed between 2016 and 2018 were identified in the National Cancer Database. Multiple imputations by chained equations were used to account for missing data, and the inverse probability of treatment weighting (IPTW) method was used to eliminate selection bias. Overall survival (OS) was compared by adjusted Kaplan-Meier curves and log-rank test with IPTW., Results: A total of 767 GI-NEC patients with nonresected liver metastases were identified. Among all patients, 177 (23.1%) received PTR and had a significantly favorable OS before (median: 43.6 months [interquartile range, IQR, 10.3-64.4] vs. 8.8 months [IQR, 2.1-23.1], p < 0.001 in log-rank test) and after (median: 25.7 months [IQR, 10.0-64.4] vs. 9.3 months [IQR, 2.2-26.4], p < 0.001 in IPTW-adjusted log-rank test) the IPTW adjustment. Additionally, this survival advantage persisted in an adjusted Cox model (IPTW adjusted hazard ratio = 0.431, 95% confidence interval: 0.332-0.560; p < 0.001). The improved survival persisted in subgroups stratified by primary tumor site, tumor grade, and N stage, even in the complete cohort (excluding patients with missing data)., Conclusions: PTR led to improved survival for GI-NEC patients with nonresected liver metastases regardless of primary tumor site, tumor grade, and N stage. However, the decision for PTR should be made on an individualized basis following multidisciplinary evaluation., (© 2023 Wiley Periodicals LLC.)

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor and remains a fatal malignancy in the majority of patients. Approximately 20%-30% of patients are eligible for resection, which is considered the only potentially curative treatment; and, after resection, a median survival of 53 months has been reported when sequenced with adjuvant capecitabine. For the 70%-80% of patients who present with locally unresectable or distant metastatic disease, systemic therapy may delay progression, but survival remains limited to approximately 1 year. For the past decade, doublet chemotherapy with gemcitabine and cisplatin has been considered the most effective first-line regimen, but results from the recent use of triplet regimens and even immunotherapy may shift the paradigm. More effective treatment strategies, including those that combine systemic therapy with locoregional therapies like radioembolization or hepatic artery infusion, have also been developed. Molecular therapies, including those that target fibroblast growth factor receptor and isocitrate dehydrogenase, have recently received US Food and Drug Administration approval for a defined role as second-line treatment for up to 40% of patients harboring these actionable genomic alterations, and whether they should be considered in the first-line setting is under investigation. Furthermore, as the oncology field seeks to expand indications for immunotherapy, recent data demonstrated that combining durvalumab with standard cytotoxic therapy improved survival in patients with ICC. This review focuses on the current and future strategies for ICC treatment, including a summary of the primary literature for each treatment modality and an algorithm that can be used to drive a personalized and multidisciplinary approach for patients with this challenging malignancy., (© 2022 The Authors. CA: A Cancer Journal for Clinicians published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Despite a steady decline in incidence and mortality rates, colorectal cancer (CRC) remains the second most common cancer diagnosis in women and the third most common in men worldwide. Notably, the liver is recognized as the most common site of CRC metastasis, and metastases to the liver remain the primary driver of disease-specific mortality for patients with CRC. Although hepatic resection is the backbone of curative-intent treatment, management of CRLM has become increasingly multimodal during the last decade and includes the use of downstaging chemotherapy, ablation techniques, and locoregional therapy, each of which are reviewed herein., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Hepatic artery infusion (HAI) is a liver-directed therapy that delivers high-dose chemotherapy to the liver through the hepatic arterial system for colorectal liver metastases and intrahepatic cholangiocarcinoma. Utilization of HAI is rapidly expanding worldwide., Objective and Methods: This review describes the conduct of HAI pump implantation, with focus on common technical pitfalls and their associated solutions. Perioperative identification and management of common postoperative complications is also described., Results: HAI therapy is most commonly performed with the surgical implantation of a subcutaneous pump, and placement of its catheter into the hepatic arterial system for inline flow of pump chemotherapy directly to the liver. Intraoperative challenges and abnormal hepatic perfusion can arise due to aberrant anatomy, vascular disease, technical or patient factors. However, solutions to prevent or overcome technical pitfalls are present for the majority of cases. Postoperative HAI-specific complications arise in 22% to 28% of patients in the form of pump pocket (8%-18%), catheter (10%-26%), vascular (5%-10%), or biliary (2%-8%) complications. The majority of patients can be rescued from these complications with early identification and aggressive intervention to continue to deliver safe and effective HAI therapy., Conclusions: This HAI toolkit provides the HAI team a reference to manage commonly encountered HAI-specific perioperative obstacles and complications. Overcoming these challenges is critical to ensure safe and effective pump implantation and delivery of HAI therapy, and key to successful implementation of new programs and expansion of HAI to patients who may benefit from such a highly specialized treatment strategy., Competing Interests: The authors report no conflict of interests., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Widespread implementation of HAI pump chemotherapy has been limited by logistic and feasibility concerns. Recent studies demonstrating excellent outcomes have fueled renewed enthusiasm and multiple new programs have emerged. This survey aims to identify barriers critical to establish a successful HAI program., Methods: Using SurveyMonkey™, a 17-question survey assessing factors required for establishing a successful program was developed by 12 HAI Consortium Research Network (HCRN) surgical oncologists. Content analysis was used to code textual responses. Frequency of categories and average rank scores for each choice were calculated., Results: Twenty-eight HCRN members responded to the survey. Implementation time varied, with 15 institutions requiring less than a year. Most programs (n = 17) became active in the past 5 years. Medical and surgical oncology were ranked most important for building a program (average ranking scores: 7.96 and 6.59/8). Administrative or regulatory approval was required at half of the institutions. The top 3 challenges faced when building a program were related to regulatory approval (6.65/9), device/equipment access (6.33/9), and drug (FUDR) access (6.25/9)., Conclusion: Development of successful programs outside of historically established centers is feasible and requires a multidisciplinary team. Future collaborative efforts are critical for sustainability of safe/effective new programs., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Intrahepatic cholangiocarcinoma (ICC) remains a deadly malignancy lacking systemic therapies for advanced disease. Recent advancements include selective FGFR1-3 inhibitors for the 15% of ICC patients harboring fusions, although survival is limited by poor response and resistance. Herein we report generation of a patient-derived FGFR2 fusion-positive ICC model system consisting of a cell line, organoid, and xenograft, which have undergone complete histologic, genomic, and phenotypic characterization, including testing standard-of-care systemic therapies. Using these FGFR2 fusion-positive ICC models, we conducted an unbiased high-throughput small molecule screen to prioritize combination strategies with FGFR inhibition, from which HDAC inhibition together with pemigatinib was validated in vitro and in vivo as a synergistic therapy for ICC. Additionally, we demonstrate broad utility of the FGFR/HDAC combination for other FGFR fusion-positive solid tumors. These data are directly translatable and justify early phase trials to establish dosing, safety, and therapeutic efficacy of this synergistic combination., (© 2022. The Author(s).)

Background: Standard of care for resectable pancreatic cancer is a combination of surgical resection (SR) and multiagent chemotherapy (MCT). We aim to determine whether SR or MCT is associated with superior survival for patients receiving only single-modality therapy., Methods: Patients with stage I-IIb pancreatic head adenocarcinoma who received either MCT or SR were identified in the NCDB (2013-2015). Following a piecewise approach to estimating hazards over the course of follow-up, conditional overall survival (OS) at 30, 60, and 90 days after treatment initiation was estimated using landmark analyses., Results: 3103 patients received MCT alone (60.3%) and 2043 underwent SR alone (39.7%). SR had an OS disadvantage at 30 (HR 3.99, 95% CI 3.12-5.11) and 60 days (HR 1.85, 95% CI 1.4-2.45), but an OS advantage after 90 days (HR 0.59, 95% CI 0.55-0.64). In a landmark analysis conditioned on 90 days survival post treatment initiation, median OS was improved for SR (17.0 vs. 12.2 months, p < 0.0001); SR improved 3-year OS by 21.3% (p < 0.05), despite patients being older (median 72 vs. 67 years, p < 0.0001) with higher Charlson-Deyo comorbidity scores (≥2: 11.2 vs. 8.6%, p = 0.006)., Conclusion: For patients with resectable pancreatic cancer, SR is associated with superior long-term survival compared to MCT., (Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Colorectal liver metastases (CRLM) are the most common cause of disease-specific mortality in patients with colorectal cancer. Hepatic artery infusion (HAI) combined with systemic chemotherapy improves survival for these patients. The safety of colorectal resection at the time of HAI pump placement has not been well established., Methods: Patients with CRLM who underwent combined HAI pump placement and colorectal (primary) resection or HAI pump placement alone were evaluated for perioperative outcomes, pump-specific complications, infectious complications, and time to treatment initiation. These outcomes were compared using comparative statistics., Results: Patients who underwent combined HAI pump placement and primary resection (n = 19) vs HAI pump placement alone (n = 13) had similar demographics and rates of combined hepatectomy. Combined HAI pump placement and primary resection group had similar operative time and blood loss (both p = NS), but longer length of stay (6 vs 4 days, p = 0.02) compared to pump placement alone. Overall postoperative complications (21% vs 8%) and pump-specific complications (16% vs 31%) were similar (both p = NS). Infection rates were not different between groups, nor was time to initiation of HAI therapy (19 vs 16 days p = NS), or systemic therapy (34 vs 35 days p = NS)., Conclusion: Combining colorectal resection with HAI pump implantation is a safe surgical approach for management of unresectable CRLM. Postoperative complications, specifically infectious complications, were not increased, nor was there a delay to initiation of HAI or systemic chemotherapy. Investigation of long-term oncologic outcomes for HAI pump placement and primary tumor resection in patients with unresectable CRLM is ongoing., (© 2021. The Society for Surgery of the Alimentary Tract.)

Background: The aim of the present study was to evaluate the impact of routine NGT decompression after PD on postoperative outcomes in the era of an enhanced recovery after surgery (ERAS) protocol., Materials and Methods: A retrospective review of all patients undergoing PD between January 2015 and October 2017 at our institution was performed comparing routine post-operative NGT decompression versus omission. The incidence of delayed gastric emptying, post-operative pancreatic fistula, hospital length of stay, operative time, 30-day readmission rate as well the time to first oral intake were evaluated., Results: Out of 149 patients who underwent PD, 65 maintained post-operative NGT decompression while post-operative NGT decompression was omitted in 84 patients. No differences were noted in delayed gastric emptying rates (both p>0.05). The median length of stay (9 days for NGT group versus 8.5 days for no NGT group) and 30-day readmission rates (13.8% versus 15.5%, respectively) were similar (p=0.781). Compared with patients who had routine post-operative NGT placed, those who had omission of a post-operative NGT had a lower need for reinsertion, shorter time to PO intake, and a lower likelihood of extended length of stay., Conclusions: In the era of ERAS protocols, we observed no association between routine post-operative NGT decompression after PD and improved postoperative outcomes., Competing Interests: Conflict of interest None declared., (Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Hepatic arterial infusion (HAI) entails the surgical implantation of a subcutaneous pump to deliver chemotherapeutic agents directly to the liver in the setting of primary or secondary liver cancer. The purpose of HAI chemotherapy is to maximize hepatic drug concentrations while minimizing systemic toxicity, facilitating more effective treatment. HAI is used in combination with systemic chemotherapy and can be considered in several clinical scenarios, including adjuvant therapy, conversion of unresectable disease to resectable disease, and unresectable disease. Radiologists are key members of the multidisciplinary team involved in the selection and management of these patients with complex liver disease. As these devices begin to be used at more sites across the country, radiologists should become familiar with the guiding principles behind pump placement, expected imaging appearances of these devices, and potential associated complications. The authors provide an overview of HAI therapy, with a focus on the key imaging findings associated with this treatment that radiologists may encounter. © RSNA, 2021.

The scope of our study was to compare the predictive ability of American Joint Committee on Cancer (AJCC) 7th and 8th edition in gallbladder carcinoma (GBC) patients, investigate the effect of AJCC 8th nodal status on the survival, and identify risk factors associated with the survival after N reclassification using the National Cancer Database (NCDB) in the period 2005-2015. The cohort consisted of 7743 patients diagnosed with GBC; 202 patients met the criteria for reclassification and were denoted as stage ≥III by AJCC 7th and 8th edition criteria. Overall survival concordance indices were similar for patients when classified by AJCC 8th (OS c-index: 0.665) versus AJCC 7th edition (OS c-index: 0.663). Relative mortality was higher within strata of T1, T2, and T3 patients with N2 compared with N1 stage (T1 HR: 2.258, p < 0.001; T2 HR: 1.607, p < 0.001; Τ3 HR: 1.306, p < 0.001). The risk of death was higher in T1-T3 patients with Nx compared with N1 stage (T1 HR: 1.281, p = 0.043, T2 HR: 2.221, p < 0.001, T3 HR: 2.194, p < 0.001). In patients with AJCC 8th edition stage ≥IIIB GBC and an available grade, univariate analysis showed that higher stage, Charlson-Deyo score ≥ 2, higher tumor grade, and unknown nodal status were associated with an increased risk of death, while year of diagnosis after 2013, academic center, chemotherapy. and radiation therapy were associated with decreased risk of death. Chemotherapy and radiation therapy were associated with decreased risk of death in patients with T3-T4 and T2-T4 GBC, respectively. In conclusion, the updated AJCC 8th GBC staging system was comparable to the 7th edition, with the recently implemented changes in N classification assessment failing to improve the prognostic performance of the staging system. Further prospective studies are needed to validate the T2 stage subclassification as well as to clarify the association, if any is actually present, between advanced N staging and increased risk of death in patients of the same T stage.

Background: Hepatic artery infusion pump (HAIP) chemotherapy is an advanced cancer therapy for primary and secondary hepatic malignancies. The risk of concurrent hepatic and/or colorectal operations with HAIP placement is unknown. Our objective was to characterize the short-term outcomes of concurrent surgery with HAIP placement., Methods: The 2005-2017 ACS NSQIP dataset was queried for patients undergoing hepatic and colorectal operations with or without HAIP placement. Outcomes were compared for HAIP placement with different combined procedures. Patients who underwent procedures without HAIP placement were propensity score matched with those with HAIP placement. The primary outcome was 30-day death or serious morbidity (DSM). Secondary outcomes included infectious complications, wound complications, length of stay (LOS), and operative time., Results: Of 467 patients who underwent HAIP placement, 83.9% had concurrent surgery. The rate of DSM was 10.7% for HAIP placement alone, 19.2% with concurrent minor hepatic procedures, 22.1% with concurrent colorectal resection, 23.2% with concurrent minor hepatic plus colorectal procedures, 28.4% with concurrent major hepatic resection, and 41.7% with concurrent major hepatic plus colorectal resection. On matched analyses, there was no difference in DSM, infectious, or wound complications for procedures with HAIP placement compared with the additional procedure alone, but operative time (294.7 vs 239.8 min, difference 54.9, 95% CI 42.8-67.0) and LOS (6 vs 5, IRR 1.20, 95% CI 1.08-1.33) were increased., Conclusions: HAIP placement is not associated with additional morbidity when performed with hepatic and/or colorectal surgery. Decisions regarding HAIP placement should consider the risks of concurrent operations, and patient- and disease-specific factors.

Background: Hepatic artery infusion (HAI) combined with systemic chemotherapy is a treatment strategy for patients with unresectable liver-only or liver-dominant colorectal liver metastases (CRLM). Although HAI has previously been performed in only a few centers, this study aimed to describe patient selection and initial perioperative outcomes during implementation of a new HAI program., Methods: The study enrolled patients with CRLM selected for HAI after multi-disciplinary review November 2018-January 2020. Demographics, prior treatment, and perioperative outcomes were assessed. Objective hepatic response was calculated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1., Results: During a 14-month period, 21 patients with CRLM underwent HAI pump placement. Of these 21 patients, 20 (95%) had unresectable disease. Most of the patients had synchronous disease (n = 18, 86%) and had received prior chemotherapy (n = 20, 95%) with extended treatment cycles (median 16; interquartile range, 8-22; range, 0-66). The median number of CRLMs was 7 (range, 2-40). Operations often were performed with combined hepatectomy (n = 4, 19%) and/or colectomy/proctectomy (n = 11, 52%). The study had no 90-day mortality. The overall surgical morbidity was 19%. The HAI-specific complications included pump pocket seroma (n = 2), hematoma (n = 1), surgical-site infection (n = 1), and extrahepatic perfusion (n = 1). HAI was initiated in 20 patients (95%). The hepatic response rates at 3 months included partial response (n = 4, 24%), stable disease (n = 9, 53%), and progression of disease (n = 4, 24%), yielding a 3-month hepatic disease control rate (DCR) of 76%., Conclusion: Implementation of a new HAI program is feasible, and HAI can be delivered safely to selected patients with CRLM. The initial response and DCR are promising, even for patients heavily pretreated with chemotherapy.

Background: Musculoskeletal symptoms and injuries among surgeons are underestimated but are increasingly recognized to constitute a major problem. However, it has not been established when symptoms start and what factors contribute to the development of symptoms., Methods: A 19-question survey approved by our institution's review board, and American Council of Academic Plastic Surgery was sent to all plastic surgery residents enrolled in Accreditation Council for Graduate Medical Education-accredited plastic surgery training programs in the United States. The presence of various musculoskeletal symptoms was calculated, and predictors of these symptoms were evaluated., Results: We received 104 total responses. Ninety-four percent of residents had experienced musculoskeletal pain in the operating room. The neck was the most commonly affected area (54%) followed by the back (32%) and extremities (12%). Interestingly, 52% of responders developed these symptoms during the first 2 years of their residency. Furthermore, increasing postgraduate year level (P = 0.3) and independent versus integrated status (P = 0.6) had no correlation with pain, suggesting that symptoms began early in training.Pain symptoms were frequent for 47%, whereas 5% reported experiencing symptoms during every case. The use of a headlight correlated with frequent pain (odds ratio, 2.5; P = 0.027). The use of microscope and loupes did not correlate with frequent pain. Eighty-nine percent of responders were aware of having bad surgical posture, but only 22% had received some form of ergonomics training at their institution. Sixty-four percent of responders believe that the operating room culture does not allow them to report the onset of symptoms and ask for adjustments. This was more common among residents reporting frequent pain (odds ratio, 3.12; P = 0.009)., Conclusions: Plastic surgeons are at high risk for occupational symptoms and injuries. Surprisingly, symptoms start early during residency. Because residents are aware of the problem and looking for solutions, this suggests an opportunity for educational intervention to improve the health and career longevity of the next generation of surgeons.

Hilar cholangiocarcinoma, which represents approximately 60% of biliary tract malignancies, is increasing in incidence and presents an ongoing challenge for patients and hepatobiliary surgeons. Although the majority of patients present with advanced disease, the remaining minority of patients are best treated with surgical resection or transplant. Transplant is typically reserved for locally unresectable tumors often in the setting of underlying hepatic dysfunction and will not be discussed herein. This review, therefore, focuses on oncological resection and the strategies implemented for the treatment of hilar cholangiocarcinoma at a quaternary referral center, including preoperative considerations such as patient selection and optimization of the future liver remnant, nuances to the operative approach for these tumors such as resection under low central venous pressure and management of the bile duct, as well as postoperative management.