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BACKGROUND: Thermal 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. METHODS: We 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). RESULTS: The 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). CONCLUSION: For 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.

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BACKGROUND: This 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. METHODS: An 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). RESULTS: R1 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). CONCLUSION: R1 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.

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BACKGROUND: Subungual melanoma (SUM) is a rare tumor with historically poor outcomes. Thus, the benefit of proximal versus distal amputation in SUM remains unclear. METHODS: We performed a retrospective review of our prospectively-maintained institutional melanoma database, including SUM and non-subungual acral melanoma (AM) patients who underwent sentinel lymph node biopsy (SLNB) between 1999 and 2022. All SUMs had distal joint or proximal amputations. Primary endpoints were overall survival (OS) and recurrence free survival (RFS). Kaplan-Meier estimates, and Cox univariate and multivariate analyses were performed. Tests were repeated on propensity score matched (PSM) populations in a 2:1 ratio. RESULTS: 123 patients underwent resection with SLNB for SUM (n â€‹= â€‹27) and AM (n â€‹= â€‹96). Median follow-up was 9.2 years. Unadjusted median OS was 149.1 months for AM and 198.1 months for SUM. In the PSM comparison, median OS and RFS remained comparable between SUM and AM (149.5 months versus 198.1 months; p â€‹= â€‹0.612). Sentinel node positivity was associated with significantly worse overall survival outcome (Hazard Ratio 5.49; CI (1.59-18.97), p â€‹= â€‹0.007). In the PSM population, male sex was also associated with a significant hazard of death (HR 3.00, CI (1.03-8.71), p â€‹= â€‹0.043). Proximal amputations were associated with significantly worse OS (p â€‹< â€‹0.002) and RFS (p â€‹< â€‹0.01) compared to distal amputations in SUM. CONCLUSION: SUM was well-treated with distal amputations, and had better OS and RFS compared to SUM treated with proximal amputations. Sentinel lymph node status is an important prognostic factor for SUMs and AMs. SUMs can be treated similarly to AMs with comparably good long-term outcomes.

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Healthy human skin tissue is often used as a control for comparison to diseased skin in patients with skin pathologies, including skin cancers or other inflammatory conditions such as atopic dermatitis or psoriasis. Although non-affected skin from these patients is a more appropriate choice for comparison, there is a paucity of studies examining such tissue. This lack is exacerbated by the difficulty of processing skin tissue for experimental analysis. In addition, choosing a processing protocol for skin tissue which preserves cell viability and identity while sufficiently dissociating cells for single-cell analysis is not a trivial task. Here, we compare three digestion methods for human skin tissue, evaluating the cell yield and viability for each protocol. We find that the use of a sequential dissociation method with multiple enzymatic digestion steps produces the highest cell viability. Using single-cell sequencing, we show this method results in a relative increase in the proportion of non-antigen-presenting mast cells and CD8 T cells as well as a relative decrease in the proportion of antigen-presenting mast cells and KYNU+ CD4 T cells. Overall, our findings support the use of this sequential digestion method on freshly processed human skin samples for optimal cell yield and viability.

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BACKGROUND: The impact of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) on quality of life (QoL) for patients taking opioids and psychotropic medications preoperatively is unclear. METHODS: This study retrospectively reviewed a CRS-HIPEC single-center prospectively maintained database for 2012-2016. Demographics and clinical data on opioids/psychotropic medication use were collected via chart review. The study collected QoL outcomes at baseline, then 3, 6, and 12 months postoperatively via the Center for Epidemiologic Studies Depression Scale (CES-D), Brief Pain Inventory, Functional Assessment of Cancer Therapy, and 36-Item Short-Form Health Survey. Differences in QoL between the groups were calculated using repeated measures analysis of variance regression. Descriptive statistics and Kaplan-Meier analyses were performed. RESULTS: Of 388 patients, 44.8% were taking opioids/psychotropic medications preoperatively. At baseline, those taking opioids/psychotropic medications preoperatively versus those not taking these medications had significantly worse QoL. By 1 year postoperatively, the QoL measures did not differ significantly except for emotional functioning (e.g., no medications vs. opioids/psychotropic medications: CES-D, 5.6 vs. 10.1). Median survival did not differ significantly (opioids/psychotropic medications vs. no medications: 52.3 vs. 60.6 months; p = 0.66). At 1 year after surgery, a greater percentage of patients were taking opioids, psychotropic medications, or both than at baseline (63.2% vs. 44.8%; p < 0.001). CONCLUSION: Despite worse baseline QoL, patients who took opioids/psychotropic medications had QoL scores 1 year postoperatively similar to the scores of those who did not except in the emotional domains. These data point to the potential utility of a timed psychosocial intervention to enhance emotional adaptation and further support the role of CRS-HIPEC in improving QoL.

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INTRODUCTION: Treatment of advanced pancreatic adenocarcinoma remains suboptimal. Therapeutic agents with a novel mechanism of action are desperately needed; one such novel agent is CPI-613 targets. We here analyze the outcomes of 20 metastatic pancreatic cancer patients treated with CPI-613 and FOLFIRINOX in our institution and evaluate their outcomes to borderline-resectable patients treated with curative surgery. METHODS: A post hoc analysis was performed of the phase I CPI-613 trial data (NCT03504423) comparing survival outcomes to borderline-resectable cases treated with curative resection at the same institution. Survival was measured by overall survival (OS) for all study cases and disease-free survival (DFS) for resected cases with progression-free survival for CPI-613 cases. RESULTS: There were 20 patients in the CPI-613 cohort and 60 patients in the surgical cohort. Median follow-up times were 441 and 517 days for CPI-613 and resected cases, respectively. There was no difference in survival times between CPI-613 and resected cases with a mean OS of 1.8 versus 1.9 year (p = 0.779) and mean PFS/DFS of 1.4 versus 1.7 years (p = 0.512). There was also no difference in 3-year survival rates for OS (hazard ratio [HR] = 1.063, 95% confidence interval [CI] 0.302-3.744, p = 0.925) or DFS/PFS (HR = 1.462, 95% CI 0.285-7.505, p = 0.648). CONCLUSION: The first study to evaluate the survival between metastatic patients treated with CPI-613 versus borderline-resectable cases undergoing curative resection. Analysis revealed no significant differences in survival outcomes between the cohorts. Study results are suggestive that there may be potential utility with the addition of CPI-613 to potentially resectable pancreatic adenocarcinoma, although additional research with more comparable study groups are required.

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INTRODUCTION: There is a paucity in the literature in regard to the incidence, risk factors, and outcomes for post-operative cholangitis following hepatic resection. METHODS: Retrospective review of the ACS NSQIP main and targeted hepatectomy registries for 2012-2016. RESULTS: A total of 11,243 cases met the selection criteria. The incidence of post-operative cholangitis was 0.64% (151 cases). Multivariate analysis identified several risk factors associated with the development of post-operative cholangitis, stratified out by pre-operative and operative factors. The most significant risk factors were biliary anastomosis and pre-operative biliary stenting with odds ratios (OR) of 32.39 (95% CI 22.91-45.79, P value < 0.0001) and 18.32 (95% CI 10.51-31.94, P value < 0.0001) respectively. Cholangitis was significantly associated with post-operative bile leaks, liver failure, renal failure, organ space infections, sepsis/septic shock, need for reoperation, longer length of stay, increased readmission rates, and death. CONCLUSION: Largest analysis of post-operative cholangitis following hepatic resection. While a rare occurrence, it is associated with significantly increased risk for severe morbidity and mortality. The most significant risk factors were biliary anastomosis and stenting.

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INTRODUCTION: Complete resection of colorectal liver metastasis (CLM) improves long-term survival in colorectal cancer. However, there is limited recent data on conditional survival (CS) as postoperative survival milestones are achieved post-hepatectomy. METHODS: A retrospective analysis was performed on the penta-institutional Colorectal Liver Operative Metastasis International Collaborative (COLOMIC), with 906 consecutive CLM hepatectomy cases. CS was calculated using Bayes' theorem and Kaplan-Meier analysis. Additional CS analyses were performed on additional clinicopathologic risk factors, including colon cancer laterality, KRAS mutation status, and extrahepatic disease. RESULTS: The 5-year CS was 40.6%, 45.3%, 52.8%, and 65.3% at 0, 1, 2, and 3 years postoperatively, with significant improvements each year (p < 0.005). CS was not significantly different between right-sided and left-sided colorectal cancers by 3 years postoperatively. Patients with KRAS mutations had worse CS at all timepoints (p < 0.001). Extrahepatic disease was a poor prognostic factor for OS and CS (p < 0.001). However, CS for patients with KRAS mutations or extrahepatic disease improved significantly as 2-year, postoperative survival was achieved (p < 0.05). CONCLUSIONS: Five-year CS after hepatectomy for CLM improved with each passing year of survival postoperatively. Although extrahepatic disease and KRAS mutations are poor prognostic factors for OS, these populations still had improved CS after 2 years postoperatively.

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BACKGROUND: Although colorectal hepatic metastases (HM) and peritoneal surface disease (PSD) are distinct biologic diseases, they may have similar long-term survival when optimally treated with surgery. METHODS: This study retrospectively reviewed prospectively managed databases. Patients undergoing R0 or R1 resections were analyzed with descriptive statistics, the Kaplan-Meier method, and Cox regression. Survival was compared over time for the following periods: 1993-2006, 2007-2012, and 2013-2020. RESULTS: The study enrolled 783 HM patients undergoing liver resection and 204 PSD patients undergoing cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). Compared with PSD patients, HM patients more often had R0 resections (90.3% vs. 32.4%), less often had pre-procedure chemotherapy (52.4% vs. 92.1%), and less often were functionally independent (79.7% vs. 95.6%). The 5-year overall survival for HM was 40.9%, with a median survival period of 45.8 months versus 25.8% and 33.4 months, respectively, for PSD (p < 0.05). When stratified by resection status, R0 HM and R0 PSD did not differ significantly in median survival (49.0 vs. 45.4 months; p = 0.83). The median survival after R1 resection also was similar between HM and PSD (32.6 vs. 26.9 months; p = 0.59). Survival between the two groups again was similar over time when stratified by resection status. The predictors of survival for HM patients were R0 resection, number of lesions, intraoperative transfusion, age, and adjuvant chemotherapy. For the PSD patients, the predictors were peritoneal cancer index (PCI) score, estimated blood loss (EBL), and female gender. CONCLUSION: The study showed that R0 resections are associated with improved outcomes and that median survival is similar between HM and PSD patients when it is achieved. Surveillance and treatment strategies that facilitate R0 resections are needed to improve results, particularly for PSD.

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BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare diagnosis with a dismal prognosis if untreated. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is shown to significantly improve survival. Our institution is uniquely positioned to report long-term outcomes in MPM with CRS-HIPEC, due to our robust peritoneal surface disease program existing over the past three decades. METHODS: Our prospectively maintained, single-institution database of CRS-HIPEC cases was reviewed, identifying 111 consecutive patients with MPM over 28 years (1993-2021). Prognostic, operative, and pathologic factors were reviewed. Overall survival (OS) and conditional survival (CS) analyses were performed. RESULTS: The average age was 55.1 years; 58.6% of patients were male; 17 of 111 patients (15.3%) had a second CRS-HIPEC. At first CRS-HIPEC, the average PCI score was 18.7, and the perfusate drugs were platinum-based (72.1%) and mitomycin C (27.9%). The resection status at first CRS-HIPEC was R2a (46.4%), followed by R0-1 (29.1%), and R2b-c (24.5%). Median OS was 3.3 years for the entire cohort, with 75th and 25th percentiles at 10.7 months and 10.6 years. Median CS was improved if patients survived to the 1-year postoperative mark (4.9 years, p < 0.01) and trended toward further improvement with each passing year. If 3-year postoperative survival was achieved, the median CS improved to 6.1 years. CONCLUSIONS: This represents one of the largest and lengthiest, single-center, longitudinal, case series of peritoneal mesothelioma treated with CRS-HIPEC. The OS suggests efficacy for CRS-HIPEC for MPM. Long-term survival improves significantly after patients achieve the 1-year, postoperative mark.

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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.

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The sartorius muscle transposition flap is the traditional method of femoral vessel coverage after superficial inguinal lymphadenectomy for regionally-metastatic cancers to the inguinal lymph nodes. However, if the groin has undergone radiotherapy, the sartorius muscle is contained within the irradiated field, and may be problematic for wound healing, in addition to being thin at its insertion and intimately related to several nerves. The gracilis muscle has been used for soft tissue defects and vascular graft infections, but its utility as an alternative to the sartorius muscle flap in the setting of radiation has never been reported. Here, we report the successful use of the retroflexed gracilis muscle flap for femoral vessel coverage after superficial inguinal lymphadenectomy, in a patient who previously underwent chemoradiation for locally-metastatic anal squamous cell carcinoma to the groin. An 86-year old female presented with Stage IIIB anal squamous cell carcinoma metastatic to one left inguinal lymph node. She underwent modified Nigro protocol chemoradiation treatment, which included radiation to the inguinal node basins. A left superficial inguinal lymphadenectomy was performed with a retroflexed gracilis muscle flap to cover the femoral vessels. This was chosen over a sartorius flap because the gracilis muscle was not located within the field of radiation. Despite a subsequent groin wound infection, the gracilis muscle flap remained viable and successfully protected the major vessels. We report the gracilis muscle flap as a viable alternative to the sartorius transposition muscle flap for femoral vessel coverage after oncologic superficial inguinal lymphadenectomy in the irradiated groin.

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INTRODUCTION: Hepatobiliary malignancies present with advanced disease precluding upfront resection. Liver-directed therapy (LDT), particularly Y-90 radioembolization and transarterial chemoembolization (TACE), has become increasingly utilized to facilitate attempt at oncologic resection. However, the safety profile of preoperative LDT is limited. METHODS: Retrospective review of the ACS NSQIP main and targeted hepatectomy registries for 2014-2016. Primary objective was evaluation of outcomes between preoperative LDT cases and those that received upfront resection. RESULTS: A total of 8923 cases met selection criteria. 192 cases (2.15%) received either Y-90 or TACE prior to hepatectomy. Multivariate analysis for all study patients revealed preoperative LDT significantly increased the risk of perioperative transfusion (OR 2.19, 95% CI 1.445-3.328, P < 0.0001), sepsis (OR 2.21, 95% CI 1.104-4.411, P = 0.022), and liver failure (OR 2.72, 95% CI 1.562-4.747, P < 0.0001). Subgroup analysis found for primary hepatobiliary malignancies LDT only increased the risk for liver failure. While for secondary hepatic tumors LDT significantly increased perioperative transfusion, sepsis, cardiac failure, renal failure, liver failure, and mortality. The complication profile also significantly increased with advanced T stage. Conversely, on propensity score matching preoperative LDT did not significantly increase perioperative complications. CONCLUSION: Preoperative LDT has the potential to convert inoperable hepatic tumors into resectable disease but there is a general increased risk for significant postoperative complications, most notable liver failure. However, on controlled analysis preoperative LDT does not increase perioperative complications and should not be considered a contraindication to resection.

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INTRODUCTION: Pancreaticoduodenectomy performed with underlying hepatic disease has been reported to have increased adverse events postoperatively. This study aimed to further evaluate that association. METHODS: Retrospective review of the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) main and targeted pancreatectomy registries for 2014-2016. High-risk liver patients were defined by MELD scores, received neoadjuvant chemotherapy, and had hepatosteatosis; two separate subgroups of MELD ≥9 and ≥ 11. High-risk liver patients were then compared to control cases via propensity score matching. RESULTS: There were 156 and 132 cases that met the high-risk liver criteria for the MELD cutoffs of ≥9 and ≥ 11 respectively. Propensity score matching left 2527 cases for final adjusted analysis. On both univariate and multivariate analysis high-risk liver patients were not associated with increased adverse events following Whipple resection. Lack of association with increased adverse events held for both the ≥9 and ≥ 11 MELD score cohorts. CONCLUSION: High-risk liver patients defined by MELD scores, neoadjuvant chemotherapy utilization, and hepatosteatosis were not associated with any increased incidence of adverse events following pancreaticoduodenectomy. Patients with underlying high-risk liver disease in this study did not appear to pose as a contraindication for oncologic resection of pancreatic adenocarcinoma.

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INTRODUCTION: Patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) are commonly exposed to oxaliplatin neoadjuvant chemotherapy (NAT) regimens. The impact of systemic exposure to oxaliplatin prior to HIPEC with oxaliplatin is unknown. METHODS: We conducted a retrospective review of our institutional registry of CRS/HIPEC cases who received oxaliplatin-containing NAT, and compared patients who underwent HIPEC with oxaliplatin versus cases perfused with mitomycin C. The primary outcome was survival, defined by overall survival (OS) and disease-free survival (DFS). Subgroup analysis was performed based on primary tumor etiology and completeness of cytoreduction. RESULTS: A total of 333 cases satisfied the selection criteria-159 appendiceal primaries (all high-grade disease) and 174 colorectal cases. Thirty-one cases (9.3%) underwent HIPEC with oxaliplatin, with the remaining 302 cases (90.7%) receiving mitomycin C. Both cohorts were identical in regard to baseline characteristics, and both groups were alike in regard to NAT regimens and oxaliplatin exposure. There was no difference in survival outcomes. OS times were 2.9 (± 2.8) and 2.8 ( ± 3.6) years for oxaliplatin and mitomycin C perfusions, respectively (p = 0.94), and the 5-year OS rates were also similar at 9.7 and 18.5% (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.14-1.67, p = 0.24) for oxaliplatin and mitomycin cases, respectively. Likewise, DFS findings were similar, with survival of 2.5 (± 4.5) and 1.8 (± 2.4) years for oxaliplatin and mitomycin perfusions, respectively (p = 0.21). There was no difference in 5-year DFS rates, at 10.5 and 7.8% (OR 1.39, 95% CI 0.30-6.56, p = 0.68) for oxaliplatin and mitomycin C, respectively. Subgroup analysis found minimal discordant findings from the main results. CONCLUSION: This analysis found no discernable association with NAT oxaliplatin exposure in regard to survival outcomes following CRS/HIPEC stratified out by perfusion agent.

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