Citations

Background Pancreatoduodenectomy (PD) is the only curative treatment for pancreatic cancer. Neoadjuvant therapy (NAT) has enhanced survival, especially for downstaging advanced tumors, while also introducing complexities and new complications. Despite surgical advances, some PD attempts remain unsuccessful. The management of these cases is not well defined. This study analyzes outcomes of repeat PD performed by two high-volume surgeons following previously unsuccessful attempts. Methods We retrospectively analyzed patients with pancreatic neoplasm undergoing successful pancreaticoduodenectomy (2013-2024) at two high-volume centers under two experienced surgeons. Only cases with prior aborted PD attempts for non-metastatic disease were included. Data from institutional records provided outcomes on failure reasons, procedure timing, surgical details, and 90-day complications. Results Of the 858 PD cases, 18 patients (2.1%; 12 males, 6 females; median age 69 years) had prior unsuccessful PD attempts at other institutions. Initial tumors were borderline resectable (33.3%), resectable (22.2%), or locally advanced (22.2%). Main causes for initial failure were vascular involvement (41.2%) and tumor infiltration (17.6%). Median time between attempts was 246 days, with 77.8% receiving chemotherapy before the second attempt. The second procedure achieved R0 resection in 94.4% of cases. Major 90-day complications occurred in 23.5% of patients, with no perioperative mortality. Disease recurrence occurred in 38.9% within the first year. Conclusion Repeat PD after an aborted attempt is feasible in select patients at specialized centers. However, complication and recurrence rates emphasize the need for careful patient selection. Further research is needed to optimize management strategies.

AbstractBackgroundThis study investigates the impact of margin status after colorectal liver metastasis (CLM) resection on outcomes of patients after neoadjuvant treatment versus those who underwent upfront resection.MethodsAn international collaborative database of CLM patients who underwent surgical resection was used. Proportional hazard regression models were created for single and multivariable models to assess the relationship between independent measures and median overall survival (mOS).ResultsR1 was associated with worse OS in the neoadjuvant group (mOS: 51.8 m for R0 vs. 26.0 m for R1; HR: 2.18). In the patients who underwent upfront surgery, R1 was not associated with OS. (mOS: 46.7 m for R0 vs. 42.6 m for R1). When patients with R1 in each group were stratified by adjuvant treatment, there was no significant difference in the neoadjuvant group, while in the upfront surgery group with R1, adjuvant treatment was associated with significant improvement in OS (mOS: 42.6 m for adjuvant vs. 25.0 m for no adjuvant treatment; HR: 0.21).ConclusionR1 is associated with worse outcomes in the patients who receive neoadjuvant treatment with no significant improvement with the addition of adjuvant therapy, likely representing an aggressive tumor biology. R1 did not impact OS in patients with upfront surgery who received postoperative chemotherapy.

AbstractBackgroundThermal ablation has recently become a key therapy for the treatment of colorectal liver metastasis (CLM). However, the role of ablation in combination with resection has not yet been firmly established. We hypothesize that in patients with CLM, those who undergo liver resection with ablation (RA) have similar outcomes compared with those who undergo liver resection only.MethodsWe reviewed a multicenter international database of 906 surgical procedures for CLM from 5 high volume hepatobiliary surgical units. Patients undergoing RA (n = 63) were matched based on the number of lesions and tumor size using a 1:1 balanced propensity score analysis with those having resection only (n = 63). Our primary outcomes were overall survival (OS) and disease‐free survival (DFS).ResultsThe mean age of our cohort was 58 ± 11 years, with 43% females. With a median follow‐up of 70.8 months, patients in the resection and RA group had a median OS of 45.1 and 54.8 months (p = 0.71), respectively. The median DFS was 22.7 and 14.2 months (p = 0.045), respectively. Using a multivariate Cox proportional hazards regression model, the treatment approach was not associated with OS (p = 0.94) or DFS (p = 0.059). A higher number of lesions is independently associated with worse DFS (hazard ratio: 1.12, p < 0.01). When there was disease recurrence, the region of recurrence was similar between the RA versus resection only groups (p = 0.27), but there was a shorter time to recurrence in the RA group (p = 0.002).ConclusionFor CLM, the treatment approach was not significantly associated with OS or DFS, while tumor biology likely played an important role. Prospective research on the quality and effectiveness of thermal ablation combined with hepatic resection is warranted.

Introduction: Lymph-nodal involvement (N+) represents an adverse prognostic factor after pancreatoduodenectomy (PD) for pancreatic adenocarcinoma (PDAC). Preoperative diagnostic and staging modalities lack sensitivity for identifying N+. This study aimed to investigate preoperative carbohydrate antigen 19.9 (CA 19.9) in predicting the N+ stage in resectable-PDAC (R-PDAC). Methods: Patients included in a multi-institutional retrospective database of PDs performed for R-PDAC from January 2000 to June 2021 were analysed. A preoperative laboratory value of CA 19.9 greater than 37 U/l was used in univariate and multivariate logistic regression analysis to determine a possible association with N+. Additionally, different cut-offs of CA 19.9 related to the preoperative clinical T (cT) stage was assessed to evaluate the risk of N+. Results: A total of 2034 PDs from thirteen centres were included in the study. CA 19.9 greater than 37 U/l was significantly associated with higher N+ at univariate and multivariate analysis ( P <0.001). CA 19.9 levels greater than 37 U/l were associated with N+ in 75.9%, 81.3%, and 85.7% of patients, respectively, in cT1, cT2, and cT3 tumours and with higher cut-off values for all cT stages. Conclusion: Lymph-nodal involvement is strongly related to preoperative CA 19.9 levels. Specially in patients staged as cT3 the CA 19.9 could represent a valid and easy tool to suspect nodal involvement. Due to these findings, R-PDAC patients with elevated CA 19.9 values should be considered in a more biologically advanced stage.

PURPOSE Pancreatic cancer (PC) carries a poor prognosis with high rates of unresectable/metastatic disease at diagnosis, recurrence after resection, and few systemic therapy options. Deficient mismatch repair (dMMR)/high microsatellite instability (MSI-H) PCs demonstrated uncharacteristically poor outcomes in KEYNOTE-158, evaluating pembrolizumab in MSI-H solid tumors. Our study aggregates the Mayo Clinic experience with dMMR/MSI-H PCs, characterizing the clinical, molecular, and treatment response patterns with a focus on response to immune checkpoint inhibitors (ICIs). METHODS Retrospective data were collected from the electronic medical record from December 2009 to February 2023. Patients were included if they had a pathologically confirmed pancreatic malignancy and had (1) deficient expression of mismatch repair (MMR) proteins by tumor immunohistochemistry, (2) pathogenic mutation of MMR genes on genomic sequencing, and/or (3) MSI-H by polymerase chain reaction. RESULTS Thirty-two patients were identified for inclusion, with all stages of disease represented. Sixteen of these patients underwent surgery or chemoradiotherapy. Of these patients, uncharacteristically favorable responses were seen, with a recurrence rate of only 19% (n = 3) despite a median follow-up of 25 months. In the palliative setting, excellent responses to ICI were seen, with overall response rate (ORR) of 75% (20% complete response). Median time to disease progression was not reached. Response rates to cytotoxic chemotherapy in the palliative setting were poor, with 30% ORR and median time to progression of 4 months. We observed a high rate of discrepancy between MMR and MSI testing methods, representing 19% of the entire cohort and 26% of evaluable cases. CONCLUSION Our data argue for the preferential use of ICI over cytotoxic chemotherapy in any patient with dMMR/MSI-H PC requiring systemic therapy, including in the metastatic and adjuvant/neoadjuvant settings.

Abstract Purpose To compare the outcomes between patients with cirrhosis and those without who have undergone pancreatoduodenectomy (PD) in our institution. Methods A review of patients undergoing PD from the time period of January 2010 to December 2020 was performed. Patients that have undergone open or laparoscopic PD and had liver cirrhosis diagnosed prior to surgery were included and matched on a 1:2 basis with non-cirrhotic patients based on age, gender, Eastern Cooperative Oncology Group (ECOG) and date of surgery. Data was obtained from our medical records and ten major postoperative complications variables were compared to the matched group. Results Overall, 16 patients with cirrhosis were compared to 32 matched controls. No significant differences were found in pancreatic fistula (18.8% vs. 21.8%; P = 1.000), hemorrhage (6.3% vs. 6.2%; P = 1.000), delayed gastric emptying (6.3% vs. 15.6%; P = 0.648), wound infection (0% vs. 9.3%; P = 0.541) intraabdominal abscess (31.2% vs 6.2%; 0.4998) for cirrhotic vs. non-cirrhotic respectively. There were no postop ileus, gastric fistula, mesenteric portal thrombosis, biliary fistula, abdominal ischemic event in either group. The average length of stay for both groups was similar (6.9 vs. 9.3 days; P = 0.4019). There were no mortalities and major morbidity was similar (37.5% vs 34.3%;P = 0.3549). One patient required readmission for liver-related decompensation with full recovery. Conclusion PD in patients with cirrhosis can be safe and feasible in well-selected patients. In a high-volume institution, postoperative complications are similar to those patients without cirrhosis of the liver

BACKGROUND: Surgical intervention remains the cornerstone of a multidisciplinary approach in the treatment of colorectal liver metastases (CLM). Nevertheless, patient outcomes vary greatly. While predictive tools can assist decision-making and patient counseling, decades of efforts have yet to result in generating a universally adopted tool in clinical practice. STUDY DESIGN: An international collaborative database of CLM patients who underwent surgical therapy between 2000 and 2018 was used to select 1,004 operations for this study. Two different machine learning methods were applied to construct 2 predictive models for recurrence and death, using 128 clinicopathologic variables: gradient-boosted trees (GBTs) and logistic regression with bootstrapping (LRB) in a leave-one-out cross-validation. RESULTS: Median survival after resection was 47.2 months, and disease-free survival was 19.0 months, with a median follow-up of 32.0 months in the cohort. Both models had good predictive power, with GBT demonstrating a superior performance in predicting overall survival (area under the receiver operating curve [AUC] 0.773, 95% CI 0.743 to 0.801 vs LRB: AUC 0.648, 95% CI 0.614 to 0.682) and recurrence (AUC 0.635, 95% CI 0.599 to 0.669 vs LRB: AUC 0.570, 95% CI 0.535 to 0.601). Similarly, better performances were observed predicting 3- and 5-year survival, as well as 3- and 5-year recurrence, with GBT methods generating higher AUCs. CONCLUSIONS: Machine learning provides powerful tools to create predictive models of survival and recurrence after surgery for CLM. The effectiveness of both machine learning models varies, but on most occasions, GBT outperforms LRB. Prospective validation of these models lays the groundwork to adopt them in clinical practice.

AbstractBackgroundThe aim of this study is to report the feasibility and short‐term outcomes of pancreaticoduodenectomy (PD) in patients who have undergone orthotopic liver transplantation (OLT).MethodsWe performed a retrospective review of a prospectively maintained pancreatic surgical database for all patients undergoing pancreaticoduodenectomy (PD) after liver transplant from January 1995 until June 2022. Demographics, indications for pancreatic resection, liver transplant and time from liver transplant to PD were reported. Operative mortality and morbidity were recorded within 90 days of surgery. Continuous variables were recorded as mean and range, while categorical variables were summarized using frequency and percentage. Postoperative complications within 90 days from PD were graded based on Clavien–Dindo classification with major complication recorded as grade IIIa or higher. Additionally, a comprehensive literature review was performed.ResultsA total of 916 patients who underwent PD at our institution between January 1995 and June 2022 were identified, and 9 patients had previous OLT. Five patients were females and 4 males with a mean age of 65 years (range 51–78). Average body mass index (BMI) was 30.8. Two patients had major complications, and three patients had minor complications. No clinically relevant POPF, PPH or DGE were observed. One patient died within 90 days from PD due to ischemic biliary pancreatic limb causing intrabdominal sepsis.ConclusionAlthough uncommon, PD after OLT is feasible with acceptable outcomes at high volume institutions and if performed by experienced surgeons.

AbstractBackgroundResection of colorectal liver metastasis (CLM) is beneficial when feasible. However, the benefit of second hepatectomy for hepatic recurrence in CLM remains unclear.MethodsThe Colorectal Liver Operative Metastasis International Collaborative retrospectively examined 1004 CLM cases from 2000 to 2018 from a total of 953 patients. Hepatic recurrence after initial hepatectomy was identified in 218 patients. Kaplan–Meier analysis was performed for overall survival (OS) and recurrence‐free survival (RFS). Propensity score matching (PSM) was performed to offset selection bias. Cox proportional‐hazards regression was performed to identify risk factors associated with OS.ResultsA total of 51 patients underwent second hepatectomy. Unadjusted median OS was 60.1 months in repeat‐hepatectomy versus 38.3 months in the single‐hepatectomy group (p = 0.015). In the PSM population, median OS remained significantly better in the repeat‐hepatectomy group (60.1 vs. 33.1 months; p = 0.0023); median RFS was 12.4 months for the repeat‐hepatectomy group, versus 9.8 months in the single‐hepatectomy group (p = 0.0050). Repeat hepatectomy was associated with lower risk of death (hazard ratio: 0.283; p = 0.000012). Obesity, tobacco use, and high intraoperative blood loss were associated with significant risk of death (p < 0.05).ConclusionIn CLM with hepatic recurrence, second hepatectomy was beneficial for OS. With PSM, the OS benefit of performing a second hepatectomy remained significant.