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Objectives Orthotopic liver transplantation (OLT) is the preferred treatment for hepatocellular carcinoma (HCC) in select patients. Many patients listed for OLT have a history of prior upper abdominal surgery (UAS). Repeat abdominal surgery increases operative complexity and may cause a greater incidence of complication. This study sought to compare outcomes after liver transplantation for patients with and without prior UAS. Methods Adult HCC patients undergoing OLT were identified using the database from the Organ Procurement and Transplantation Network (1987–2015). Patients were separated by presence of prior UAS into 2 propensity-matched cohorts. Overall survival (OS) and graft survival (GS) were analyzed by log-rank test and graphed using Kaplan-Meier method. Recipient and donor demographic and clinical characteristics were also studied using Cox regression models. Results A total of 15,043 patients were identified, of whom 6,205 had prior UAS (41.2%). After 1:1 propensity score matching, cohorts (UAS versus no UAS) contained 4,669 patients. UAS patients experienced shorter GS (122 months vs 129 months; P  < .001) and shorter OS (130 months vs 141 months; P  < .001). Median duration of stay for both cohorts was 8 days. Multivariate Cox regression models revealed that prior UAS was associated with an increased hazard ratio (HR) for GS (HR 1.14; 95% confidence interval (CI) 1.06–1.22; P  < .001) and OS (HR 1.14; 95% CI 1.06–1.23; P  < .001). Conclusion Prior UAS is an independent negative predictor of GS and OS after OLT for HCC. OLT performed in patients with UAS remains a well-tolerated and effective treatment for select HCC patients but may alter expected outcomes and influence follow-up protocols. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to determine the prognostic value of embryonic origin in patients undergoing resection after chemotherapy for colon cancer liver metastases (CCLM). Methods: We identified 725 patients with primary colon cancer and known RAS mutation status who underwent hepatic resection after preoperative chemotherapy for CCLM (1990 to 2015). Survival after resection of CCLM from midgut origin (n = 238) and hindgut origin (n = 487) was analyzed. Predictors of pathologic response and survival were determined. Prognostic value of embryonic origin was validated with a separate cohort of 252 patients with primary colon cancer who underwent resection of CCLM without preoperative chemotherapy. Results: Recurrence-free survival (RFS) and overall survival (OS) after hepatic resection were worse in patients with midgut origin tumors (RFS rate at 3 years: 15% vs 27%, P < 0.001; OS rate at 3 years: 46% vs 68%, P < 0.001). Independent factors associated with minor pathologic response were midgut embryonic origin [odds ratio (OR) 1.55, P = 0.010], absence of bevacizumab (OR 1.42, P = 0.034), and mutant RAS (OR 1.41, P = 0.043). Independent factors associated with worse OS were midgut embryonic origin [hazard ratio (HR) 2.04, P < 0.001], carcinoembryonic antigen value ≥5 ng/ mL at hepatic resection (HR 1.46, P = 0.0021), synchronous CCLM (HR 1.45, P = 0.012), and mutant RAS (HR 1.43, P = 0.0040). In the validation cohort, patients with CCLM of midgut origin had a worse 3-year OS rate (55% vs 78%, P = 0.003). Conclusions: Compared with CCLM from hindgut origin, CCLM from midgut origin are associated with worse pathologic response to chemotherapy and worse survival after resection. This effect appears to be independent of RAS mutation status. [ABSTRACT FROM AUTHOR]

Background Operative resection remains the definitive curative therapy for retroperitoneal sarcoma. Data published recently show a correlation between improved outcomes for complex oncologic operations and treatment at academic centers. For large retroperitoneal sarcomas, operative resection can be complex and require multidisciplinary care. We hypothesized that survival rates vary between type of treating center for patients undergoing resection for retroperitoneal sarcoma. Methods Patients with stage I to III nonmetastatic retroperitoneal sarcomas who underwent operative resection were identified from the National Cancer Database during the years 2004–2013. Treating centers were categorized as academic cancer centers or community cancer centers. Overall survival was analyzed by log-rank test and graphed using Kaplan-Meier method. Results A total of 2,762 patients were identified. A majority of patients (59.4%, n = 1,642) underwent resection at an academic cancer centers. Median age at diagnosis was 63 years old. Neoadjuvant radiotherapy was more common at academic cancer centers, while adjuvant radiotherapy was more common at community cancer centers. Improved overall survival was seen at academic cancer centers across all stages compared with community cancer centers ( P = .014) but, after multivariable Cox regression analysis, was not a significant independent predictor of survival (hazard ratio = 0.91, 95% confidence interval, 0.79–1.04, P = .171). Academic cancer centers exhibited a greater rate of R0 resection (55.9% vs 47.0%, P < .001) and a lesser odds of positive margins (odds ratio 0.83, 95% confidence interval, 0.69–0.99, P = .044) after multivariable logistic regression. Conclusion Resection for retroperitoneal sarcoma performed at academic cancer centers was an independent predictor of margin-negative resection but was not a statistically significant factor for survival. This observation suggests that site of care may contribute to some aspect of improved oncologic resection for retroperitoneal sarcoma. [ABSTRACT FROM AUTHOR]

Background: The directed study of the functional proteome in colorectal cancer (CRC) has identified critical protein markers and signaling pathways; however, the prognostic relevance of many of these proteins remains unclear. Methods: We determined the prognostic implications of the functional proteome in 263 CRC tumor samples from patients treated at MD Anderson Cancer Center (MDACC) and 462 patients from The Cancer Genome Atlas (TCGA) to identify patterns of protein expression that drive tumorigenesis. A total of 163 validated proteins were analyzed by reverse phase protein array (RPPA). Unsupervised hierarchical clustering of the tumor proteins from the MDACC cohort was performed, and clustering was validated using RPPA data from TCGA CRC. Cox regression was used to identify predictors of tumor recurrence. Results: Clustering revealed dichotomization, with subtype A notable for a high epithelial-mesenchymal transition (EMT) protein signature, while subtype B was notable for high Akt/TSC/mTOR pathway components. Survival data were only available for the MDACC cohort and were used to evaluate prognostic relevance of these protein signatures. Group B demonstrated worse relapse-free survival (hazard ratio 2.11, 95% confidence interval 1.04-4.27, p = 0.039), although there was no difference in known genomic drivers between the two proteomic groups. Proteomic grouping and stage were significant predictors of recurrence on multivariate analysis. Eight proteins were found to be significant predictors of tumor recurrence on multivariate analysis: Collagen VI, FOXO3a, INPP4B, LcK, phospho-PEA15, phospho-PRAS40, Rad51, phospho-S6. Conclusion: CRC can be classified into distinct subtypes by proteomic features independent of common oncogenic driver mutations. Proteomic analysis has identified key biomarkers with prognostic importance, however these findings require further validation in an independent cohort. [ABSTRACT FROM AUTHOR]

Background The obesity epidemic has significantly increased the incidence and severity of hepatic steatosis in liver surgery patients and liver donors, potentially impacting postoperative liver regeneration and function. Development of a non-invasive means to quantify hepatic steatosis would facilitate selection of candidates for liver resection and transplant donation. Methods An IRB-approved protocol prospectively enrolled 28 patients with liver tumors requiring hepatic resection. In all patients, fast dual-echo gradient-echo MR images were acquired using 2-Point Dixon technique in 2D and 3D. The degree of steatosis was quantified by percent fat fraction (%FF) from in- and out-of-phase, and water-only and fat-only images. The technique-specific %FFs were compared to intraoperative and histopathological findings. Results For patients with >30% steatosis by histology, the mean %FF was 22% (SD ± 5.2%) compared to a mean %FF of 5.0% (SD ± 2.1%, p = 0.0001) in patients with <30% steatosis. Using scaled values for the MR-calculated %FF, all patients with >30% pathologic steatosis could be identified preoperatively. Conclusions Quantitative MRI identified patients with clinically-relevant steatosis with 100% accuracy. These findings could have significant impact on the management of liver resection patients and transplant donors. [ABSTRACT FROM AUTHOR]

Background Duty-hour regulations have increased the frequency of trainee-trainee patient handoffs. Each handoff creates a potential source for communication errors that can lead to near-miss and patient-harm events. We investigated the utility, efficacy, and trainee experience associated with implementation of a novel, standardized, electronic handoff system. Methods We conducted a prospective intervention study of trainee-trainee handoffs of inpatients undergoing complex general surgical oncology procedures at a large tertiary institution. Preimplementation data were measured using trainee surveys and direct observation and by tracking delinquencies in charting. A standardized electronic handoff tool was created in a research electronic data capture (REDCap) database using the previously validated I-PASS methodology (illness severity, patient summary, action list, situational awareness and contingency planning, and synthesis). Electronic handoff was augmented by direct communication via phone or face-to-face interaction for inpatients deemed “watcher” or “unstable.” Postimplementation handoff compliance, communication errors, and trainee work flow were measured and compared to preimplementation values using standard statistical analysis. Results A total of 474 handoffs (203 preintervention and 271 postintervention) were observed over the study period; 86 handoffs involved patients admitted to the surgical intensive care unit, 344 patients admitted to the surgical stepdown unit, and 44 patients on the surgery ward. Implementation of the structured electronic tool resulted in an increase in trainee handoff compliance from 73% to 96% ( P < .001) and decreased errors in communication by 50% ( P = .044) while improving trainee efficiency and workflow. Conclusion A standardized electronic tool augmented by direct communication for higher acuity patients can improve compliance, accuracy, and efficiency of handoff communication between surgery trainees. [ABSTRACT FROM AUTHOR]

Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with improved survival for patients with colorectal peritoneal metastases (CR-PM). However, the role of neoadjuvant chemotherapy (NAC) prior to CRS-HIPEC is poorly understood. A retrospective review of adult patients with CR-PM who underwent CRS+/-HIPEC from 2000–2017 was performed. Among 298 patients who underwent CRS+/-HIPEC, 196 (65.8%) received NAC while 102 (34.2%) underwent surgery first (SF). Patients who received NAC had lower peritoneal cancer index score (12.1 + 7.9 vs. 14.3 + 8.5, p = 0.034). There was no significant difference in grade III/IV complications (22.4% vs. 16.7%, p = 0.650), readmission (32.3% vs. 23.5%, p = 0.114), or 30-day mortality (1.5% vs. 2.9%, p = 0.411) between groups. NAC patients experienced longer overall survival (OS) (median 32.7 vs. 22.0 months, p = 0.044) but similar recurrence-free survival (RFS) (median 13.8 vs. 13.0 months, p = 0.456). After controlling for confounding factors, NAC was not independently associated with improved OS (OR 0.80) or RFS (OR 1.04). Among patients who underwent CRS+/-HIPEC for CR-PM, the use of NAC was associated with improved OS that did not persist on multivariable analysis. However, NAC prior to CRS+/-HIPEC was a safe and feasible strategy for CR-PM, which may aid in the appropriate selection of patients for aggressive cytoreductive surgery. [ABSTRACT FROM AUTHOR]

Purpose: Peak fertility commonly occurs during medical training, and delaying parenthood can complicate pregnancies. Trainee parental leave policies are varied and lack transparency. Research on the impacts of parenthood on trainee education is limited. Methods: A Qualtrics-based survey was distributed via e-mail/social media to program directors (PDs) within oncologic specialties with a request to forward a parallel survey to trainees. Questions assessed awareness of parental leave policies, supportiveness of parenthood, and impacts on trainee education. Statistical analyses included descriptive frequencies and bivariable comparisons by key groups. Results: A total of 195 PDs and 286 trainees responded. Twelve percent and 29% of PDs were unsure of maternity/paternity leave options, respectively. PDs felt they were more supportive of trainee parenthood than trainees perceived they were. Thirty-nine percent of nonparent trainees (NPTs) would have children already if not in medicine, and >80% of women trainees were concerned about declining fertility. Perceived impacts of parenthood on trainee overall education and academic productivity were more negative for women trainees when rated by PDs and NPTs; however, men/women parents self-reported equal impacts. Leave burden was perceived as higher for women trainees. Conclusions: A significant portion of PDs lack awareness of parental leave policies, highlighting needs for increased transparency. Trainees' perception of PD support for parenthood is less than PD self-reported support. Alongside significant rates of delayed parenthood and fertility concerns, this poses a problem for trainees seeking to start a family, particularly women who are perceived more negatively. Further work is needed to create a supportive culture for trainee parenthood. [ABSTRACT FROM AUTHOR]

We explored the association between weekend discharge and 30- and 90-d readmission rates in patients undergoing hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for peritoneal carcinomatosis. The US HIPEC Collaborative database, comprised of a longitudinal cohort of patients undergoing CRS/HIPEC for peritoneal carcinomatosis at twelve academic institutions between 2000 and 2017, was queried for date of discharge information. Patients were retrospectively divided into weekday and weekend/holiday discharge groups. Patients <18 y old, lacking day of discharge information, or who experienced intraoperative/in-hospital mortality were excluded. Comparisons were made between patients discharged on a weekday versus those discharged on a weekend or major holiday. 1415 patients met inclusion criteria for the study: 1108 (78%) patients with a weekday discharge and 308 (22%) with a weekend/holiday discharge. Median age at time of surgery was 55 y (Interquartile Range: 46-63); 59% (n = 841) patients were female, 25% (n = 328) of patients had high volume disease (defined as a peritoneal cancer index >20 intraoperatively), and 92% (n = 1210) of patients had a complete cytoreduction (defined as a completeness of cytoreduction score of 0 or 1). Overall, 15% (n = 218) of patients were readmitted within 30 d and 19% (n = 265) within 90 d. In a linear mixed effects model, weekend discharge was not associated with higher 30- or 90-d readmissions (P = 0.291, P = 0.743). Weekend discharges are safe following CRS/HIPEC. Length of stay initiatives should focus on discharging the patient when medically ready, rather than avoiding weekend discharge out of an abundance of caution. [ABSTRACT FROM AUTHOR]

Purpose/Objectives: Most patients with pancreatic adenocarcinoma (PDAC) will present with distant metastatic disease at diagnosis. We sought to identify clinical characteristics associated with prolonged overall survival (OS) in patients presenting with metastatic PDAC. Materials/Methods: Patients presenting with metastatic PDAC that received treatment at our institution with FOLFIRINOX or gemcitabine-based chemotherapies between August 1, 2011 and September 1, 2017 were included in the study. Metastatic disease burden was comprehensively characterized radiologically via individual diagnostic imaging segmentation. Landmark analysis was performed at 18months, and survival curves were estimated using the Kaplan– Meier method and compared between groups via the log-rank test. ECOG and Charlson Comorbidity Index (CCI) were calculated for all patients. Results: 121 patients were included with a median age of 62 years (37–86), 40% were female, 25% had ECOG 0 at presentation. Of the 121 patients included, 33% (n=41) were alive at 12months and 25% (n=31) were alive at 18months. Landmark analysis demonstrated a significant difference between patients surviving <18months and ≥18months regarding the presence of lung only metastases (36% vs. 16%, p=0.04), number of organs with metastases (≥2 vs. 1, p=0.04), and disease volume (mean of 19.1 cc vs. 1.4 cc, p=0.04). At Year 1, predictors for improved OS included ECOG status at diagnosis (ECOG 0 vs. ECOG 1, p=0.04), metastatic disease volume at diagnosis (≤0.1 cc vs. >60 cc, p=0.004), metastasis only in the liver (p=0.04), and normalization of CA 19-9 (p<0.001). At Year 2, the only predictor of improved OS was normalization of the CA 19-9 (p=0.03). In those patients that normalized their CA 19-9, median overall survival was 16months. Conclusions: In this exploratory analysis normalization of CA-19-9 or volumetric metastatic disease burden less than 0.2 cc demonstrated a remarkable OS, similar to that of patients with non-metastatic disease. These metrics are useful for counseling patients and identifying cohorts that may be optimal for trials exploring metastatic and/or local tumor-directed interventions. [ABSTRACT FROM AUTHOR]

Insurance prior authorization (PA) is a determination of need, required by a health insurer for an ordered test/procedure. If the test/procedure is denied, a peer-to-peer (P2P) discussion between ordering provider and payer is used to appeal the decision. The objective of this study was to measure the number and patterns of unnecessary PA denials. This was a retrospective review at a quaternary cancer center from October 2021 to March 2022. Included were all patients with outpatient imaging orders for surgical planning or surveillance of gastrointestinal, endocrine, or skin cancer. Primary outcome was unnecessary initial denial (UID) defined as an order that required preauthorization, was initially denied by the insurer, and subsequently overturned by P2P. Nine hundred fifty seven orders were placed and 419 required PA (44%). Of tests requiring authorization, 55/419 (13.1%) were denied. Variability in the likelihood of initial denial was seen across insurers, ranging from 0% to 57%. Following P2P, 32/55 were overturned (58.2% UID). The insurers most likely to have a UID were Aetna (100%), Anthem (77.8%), and Cigna (50.0%). UID was most common for gastrointestinal (58.9%) and endocrine (58.3%) cancers. Average P2P was 33.5 min (interquartile range 28-40). The majority of imaging studies initially denied were overturned after P2P. If all UIDs were eliminated, this would represent 108 less P2P discussions with an estimated time-savings of 60.3 h annually within a high-volume surgical oncology practice. Combined personnel costs to the health systems and stress on patients with cancer due to image-associated PAs and P2P appear hard to justify. [ABSTRACT FROM AUTHOR]

Background: Among patients with localized pancreatic cancer (PC), the benefit of adjuvant therapy after neoadjuvant therapy and surgery is unknown.Methods: Patients with localized PC who completed all intended neoadjuvant therapy and surgery were categorized based on the receipt of adjuvant therapy and by pathologic lymph node status (LN-/LN+).Results: Data was available from 234 consecutive patients, 121 (52%) with resectable and 113 (48%) with borderline resectable PC. Of the 234 patients, 92 (39%) were LN+ and 142 (61%) were LN-. The median overall survival (OS) for the 234 patients was 39 months, 42.3 months for patients who received any adjuvant therapy and 34.1 months for those who did not (p = 0.29). Of the 92 LN+ patients, the median OS with and without adjuvant therapy was 29.5 and 23.2 months, respectively (p = 0.02). Of the142 LN- patients, the median OS was 45 months with or without adjuvant therapy (p = 0.86). In an adjusted hazard model, additional adjuvant therapy had a significant protective effect among LN+ patients (HR 0.39; 95% CI 0.21-0.70; p = 0.002) but not in LN- patients (HR 0.89; 95% CI 0.53-1.52; p = 0.68).Conclusion: Among patients with localized PC who received neoadjuvant therapy and surgery, the benefit of adjuvant therapy was limited to those with node-positive disease. [ABSTRACT FROM AUTHOR]

Early postoperative mortality risk prediction is crucial for clinical management of gastric cancer. This study aims to predict 90-day mortality in gastric cancer patients undergoing gastrectomy using automated machine learning (AutoML), optimize models for preoperative prediction, and identify factors influential in prediction. National Cancer Database was used to identify stage I–III gastric cancer patients undergoing gastrectomy between 2004 and 2016. 26 features were used to train predictive models using H2O.ai AutoML. Performance on validation cohort was measured. In 39,108 patients, 90-day mortality rate was 8.8%. The highest performing model was an ensemble (AUC = 0.77); older age, nodal ratio, and length of inpatient stay (LOS) following surgery were most influential for prediction. Removing the latter two parameters decreased model performance (AUC 0.71). For optimizing models for preoperative use, models were developed to first predict node ratio or LOS, and these predicted values were inputted for 90-day mortality prediction (AUC of 0.73–0.74). AutoML performed well in predicting 90-day mortality in a larger cohort of gastric cancer patients that underwent gastrectomy. These models can be implemented preoperatively to inform prognostication and patient selection for surgery. Our study supports broader evaluation and application of AutoML to guide surgical oncologic care. [ABSTRACT FROM AUTHOR]

Effective treatment of malignant melanomas is dependent upon accurate histopathological staging of preoperative biopsy specimens. While narrow excision is the gold standard for melanoma diagnosis, superficial shave biopsies have become the preferred method by dermatologists but may transect the lesion and result in inaccurate Breslow thickness assessment. This is a retrospective cohort study evaluating an initial method of biopsy for diagnosis of cutaneous melanoma and indication for reoperation based on inaccurate initial T-staging. We retrospectively analyzed consecutive patients referred to the Medical College of Wisconsin, a tertiary cancer center, with a diagnosis of primary cutaneous melanoma. Adult patients seen between 2015 and 2018 were included. Fisher's exact test was used to assess the association between method of initial biopsy and need for unplanned reoperation. Three hundred twenty three patients with cutaneous melanoma from the head and neck (H& N , n = 101, 31%), trunk (n = 90, 15%), upper extremity (n = 84, 26%), and lower extremity (n = 48, 28%) were analyzed. Median Breslow thickness was 0.54 mm (interquartile range = 0.65). Shave biopsy was the method of initial biopsy in 244 (76%), excision in 23 (7%), and punch biopsy in 56 (17%). Thirty nine (33%) shave biopsies had a positive deep margin, as did seven (23%) punch biopsies and 0 excisional biopsies. Residual melanoma at definitive excision was found in 131 (42.5%) of all surgical specimens: 95 (40.6%) shave biopsy patients, 32 (60.4%) punch biopsy patients, and four (19.0%) excision biopsy patients. Recommendations for excision margin or sentinel lymph node biopsy changed in 15 (6%) shave biopsy patients and five (9%) punch biopsy patients. Shave biopsy is the most frequent method of diagnosis of cutaneous melanoma in the modern era. While shave and punch biopsies may underestimate true T-stage, there was no difference in need for reoperation due to T-upstaging based on initial biopsy type, supporting current diagnostic practices. Partial biopsies can thus be used to guide appropriate treatment and definitive wide local excision when adjusting for understaging. [ABSTRACT FROM AUTHOR]

Palliation is a controversial indication for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Patients with peritoneal carcinomatosis (PC) are living longer, and the roles of palliative CRS and HIPEC are increasingly challenged. The purpose of this study is to evaluate indications, morbidity, and symptom improvement from CRS/HIPEC in advanced PC. A retrospective review of patients undergoing CRS and/or HIPEC with a palliative intent at a single institution from February 2008 to February 2018 was performed. Main end points included symptom improvement, symptom-free interval, and overall survival. Two hundred and seventy seven patients were referred for CRS/HIPEC during the study period and 17 underwent 20 palliative procedures. Appendiceal (n = 6) and colorectal cancers (n = 6) were the most common malignancies. Ascites (n = 8) and bowel obstruction (n = 8) were the most common indications for intervention. The postoperative complication rate was 50% and major complication rate was 20%. Partial symptom improvement or resolution of symptoms was achieved in 18 (90%) cases. A durable symptom control at 90 d was achieved in 13 (65%) cases. The median time to symptom recurrence was 5.1 mo (interquartile range: 2-11.4), and the median overall survival was 11.6 mo (interquartile range: 3.8-28.5). Palliative CRS and/or HIPEC achieve symptom improvement in patients with advanced PC. Risk assessment and expected time to recovery from surgery remain paramount for patient selection. • Advanced peritoneal carcinomatosis (PC) can cause debilitating symptoms. • To benefit patients, palliative surgery must be safe in terms of morbidity and mortality and effective in terms of symptom relief. • In highly selected patients, palliative CRS and/or HIPEC can offer durable symptom relief. • Important factors in patient selection include patient factors, disease characteristics, and operative approach. [ABSTRACT FROM AUTHOR]

The role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with extraperitoneal disease (EPD) is controversial. Among patients with peritoneal metastases from appendiceal cancer (AC) and colorectal cancer (CRC) who underwent CRS-HIPEC, those with EPD (liver, lung, or retroperitoneal lymph nodes [RP LN]) were retrospectively compared to those without EPD. Overall (OS) and recurrence-free survival (RFS) analyses were performed before/after propensity score matching (PSM). Among 1341 patients with AC (64%) or CRC (36%) who underwent CRS ± HIPEC, 134 (10%) had EPD whereas 1207 (90%) did not. EPD was located in the lungs (47%), RP LN (28%), liver (18%), or multiple (6%). Patients with EPD experienced worse median OS (34 versus 63 mo; P = 0.002) and RFS (12 versus 19 mo; P < 0.001). On a multivariable analysis, EPD was associated with worse RFS (P = 0.003), but not OS (P = 0.071). After PSM, the association of EPD with OS (P = 0.204) and RFS (P = 0.056) was no longer significant. In the multivariable analysis of the PSM cohort, EPD was not associated with OS (P = 0.157) or RFS (P = 0.110). The findings of this large retrospective multi-institutional study suggest that EPD alone, while a negative prognostic indicator, should not be considered an absolute contraindication to CRS ± HIPEC for otherwise well-selected patients with peritoneal surface malignancies. Further research is needed to delineate whether location of EPD influences OS and RFS following CRS-HIPEC. [ABSTRACT FROM AUTHOR]

Background: Tumor markers are commonly utilized in the diagnostic evaluation, treatment decision making, and surveillance of appendiceal tumors. In this study, we aimed to determine the prognostic significance of elevated preoperative tumor markers in patients with pseudomyxoma peritonei secondary to low-grade appendiceal mucinous neoplasm who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Methods: Using a multi-institutional database, eligible patients with measured preoperative tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), or cancer antigen 125 (CA-125)] were identified. Univariate and multivariate Cox-proportional hazards regression analysis assessed relationships between normal and elevated serum tumor markers with progression-free and overall survival in the context of multiple clinicopathologic variables. Results: zTwo hundred and sixty-four patients met criteria. CEA was the most commonly measured tumor marker (97%). Patients who had any elevated tumor marker had a higher peritoneal carcinomatosis index (PCI) as compared to those with normal range markers. Elevated CEA and CA 19-9 levels were individually associated with longer inpatient length of stay, requirement for intraoperative transfusion, and incomplete cytoreduction. Utilization of neoadjuvant chemotherapy, increased PCI score, elevated CA 19-9 (p = 0.007), and CA-125 levels (p = 0.01) were predictive of decreased progression-free survival on univariate analysis. However, in a multivariate model, only elevated PCI was a statistically significant predictor of progression-free survival. Conclusion: Elevated preoperative tumor markers indicate a higher burden of disease but are not independently associated with survival in this retrospective multi-institutional cohort. Further prospective studies are needed to clarify the utility of these markers in this patient population. [ABSTRACT FROM AUTHOR]

Background: Prognostication based on preoperative clinical factors is lacking in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). This study aims to determine the value of preoperative tumor markers as predictors of progression-free survival (PFS) and overall survival (OS) for patients with peritoneal carcinomatosis from a primary mucinous adenocarcinoma of the appendix (MACA). Methods: We queried the United States HIPEC Collaborative, a database of patients with peritoneal carcinomatosis treated with CRS/HIPEC at twelve institutions between 2000 and 2017, identifying 409 patients with MACA. Multivariate analysis was used to identify independent predictors of disease progression. Subgroup analysis was conducted to evaluate the impact of tumor grade on the predictive value of tumor markers. Results: CA19-9 [HR 2.44, CI 1.2–3.4] emerged as an independent predictor of PFS while CEA [HR 4.98, CI 1.06–23.46] was independently predictive of OS (p <0.01). Tumor differentiation was the most potent predictor of both PFS (poorly differentiated vs well, [HR 4.5 CI 2.01–9.94]) and OS ([poorly differentiated vs well-differentiated: [HR 13.5, CI 3.16–57.78]), p <0.05. Among patients with combined CA19-9 elevation and poorly differentiated histology, 86% recurred within a year of CRS/HIPEC (p < 0.01). Similarly, the coexistence of CEA elevation and unfavorable histology led to the lowest survival rate at two years [36%, p < 0.01]. CA-125 was not predictive of PFS or OS. Conclusion: Elevated preoperative CA19-9 portends worse PFS, while elevated CEA predicts worse OS after CRS/HIPEC in patients with MACA. This study provides additional evidence that CA19-9 and CEA levels should be collected during standard preoperative bloodwork, while CA-125 can likely be omitted. Tumor differentiation, when added to preoperative tumor marker levels, provides powerful prognostic information. Prospective studies are required to confirm this association. [ABSTRACT FROM AUTHOR]

Current guidelines recommend genetic testing for all patients with pancreatic cancer (PC). Patients with localized PC who received neoadjuvant therapy between 2009 and 2018 were identified. Genetic consultation (including personal and family history of cancer), genetic testing, and variant data were abstracted. Of 510 patients identified, 163 (32%) underwent genetic counseling and genetic testing was performed in 127 (25%). Patients who underwent genetic testing were younger (median age: 63 vs. 67, p = 0.01). Multi-gene testing was performed in 114 (90%) of 127 patients, targeted gene testing was performed in 8 (6%), and not specified in 5 (4%). Of 127 patients who underwent genetic testing, 20 (16%) had pathogenic (P)/likely pathogenic (LP) variants, observed in ATM (n = 7/105,7%), CHEK2 (n = 3/98, 3%), BRCA1 (n = 2/117, 2%), BRCA2 (n = 2/122, 2%), PALB2 (n = 1/115, 1%), MUTYH (n = 1/98, 1%), CDKN2A (n = 1/94, 1%), STK11 (n = 1/97, 1%), NBN (n = 1/98, 1%), and MSH6 (n = 1/97, 1%). Of 20 patients with either a P/LP variant, nine (45%) had a prior cancer, three (15%) had a first-degree relative with PC, and six (30%) had an any-degree relative with PC. Pathogenic/likely pathogenic variants were identified in 16% of patients who underwent genetic testing, 60% of which occurred in the homologous recombination pathway. [ABSTRACT FROM AUTHOR]

Using a national database of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) recipients, we sought to determine risk factors for nonhome discharge (NHD) in a cohort of patients. Patients undergoing CRS/HIPEC at any one of 12 participating sites between 2000 and 2017 were identified. Univariate analysis was used to compare the characteristics, operative variables, and postoperative complications of patients discharged home and patients with NHD. Multivariate logistic regression was used to identify independent risk factors of NHD. The cohort included 1593 patients, of which 70 (4.4%) had an NHD. The median [range] peritoneal cancer index in our cohort was 14 [0-39]. Significant predictors of NHD identified in our regression analysis were advanced age (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.05-1.12; P < 0.001), an American Society of Anesthesiologists (ASA) score of 4 (OR, 2.87; 95% CI, 1.21-6.83; P = 0.017), appendiceal histology (OR, 3.14; 95% CI 1.57-6.28; P = 0.001), smoking history (OR, 3.22; 95% CI, 1.70-6.12; P < 0.001), postoperative total parenteral nutrition (OR, 3.14; 95% CI, 1.70-5.81; P < 0.001), respiratory complications (OR, 7.40; 95% CI, 3.36-16.31; P < 0.001), wound site infections (OR, 3.12; 95% CI, 1.58-6.17; P = 0.001), preoperative hemoglobin (OR, 0.81; 95% CI, 0.70-0.94; P = 0.006), and total number of complications (OR, 1.41; 95% CI, 1.16-1.73; P < 0.001). Early identification of patients at high risk for NHD after CRS/HIPEC is key for preoperative and postoperative counseling and resource allocation, as well as minimizing hospital-acquired conditions and associated health care costs. [ABSTRACT FROM AUTHOR]

Elevations in inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR) or platelet-to-lymphocyte ratio (PLR), are reportedly associated with decreased overall survival (OS) or recurrence-free survival (RFS) in patients with numerous cancers. A large multicenter sarcoma data set was used to determine if elevated NLR or PLR was associated with worse survival and can guide treatment selection. A total of 409 patients with a primary retroperitoneal sarcoma (n = 268) or truncal (n = 141) sarcoma from 2000 to 2015 were analyzed using the US Sarcoma Collaboration database. Binary NLR and PLR values were developed using receiver operating characteristic curves. Kaplan-Meier model and Cox proportional hazards model identified predictors of decreased OS and RFS. Point biserial analyses were used to correlate binary and continuous data. Neither elevated NLR nor PLR was predictive of decreased OS or RFS. These findings persisted despite exclusion of comorbid inflammatory conditions. Further, NLR and PLR were not correlated with tumor grade. In multivariate models, decreased RFS was associated with tumor factors (e.g., positive margins, tumor grade, tumor size, necrosis, positive nodes); decreased OS was associated with histologic subtype, male gender, and nodal involvement. Although several small studies have suggested that elevated NLR and PLR are associated with decreased survival in patients with abdominal or truncal sarcoma, this large multicenter study demonstrates no association with decreased OS, decreased RFS, or tumor grade. Rather, survival outcomes are best predicted using previously established tumoral factors. [ABSTRACT FROM AUTHOR]

Background: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) results in significant morbidity and readmissions. Previous studies have been limited by single-institution design or lack of tumor details in the database used.Methods: The 12-institution US HIPEC Collaborative Database was queried between 1999 and 2017. Preoperative and intraoperative patient and tumor details were analyzed for associations with readmissions.Results: A total of 2017 of 2372 cases were included in the analysis. The 30-day readmission rate was 15.9% (n = 321). Common indications for readmission included failure to thrive (29.9%), infection (23.6%), and ileus/bowel obstruction (15.1%). The readmitted cohort had more complications, including intra-abdominal abscess (21.2% vs 6.2%), ileus (28.0% vs 17.2%), anastomotic leak (11.2% vs 2.2%), enteric fistula (5.6% vs 1.5%), deep venous thrombosis (6.2% vs 2.5%), and pulmonary embolism (6.9% vs 2.5%). Factors independently associated with readmission (p < 0.05) included ECOG score ≥ 3 (OR 3.4), depression (OR 2.4), total parenteral nutrition (OR 3.6), low anterior resection or partial colectomy (OR 2.0), and stoma creation (OR 2.2). Factors not associated included neoadjuvant chemotherapy, peritoneal cancer index, and completeness of cytoreduction. Readmission rate between 31 and 90 days was 3.9% (n = 78). Independent predictors (p < 0.05) included operative time (OR 1.1), low anterior resection or partial colectomy (OR 1.7), and stoma creation (OR 2.2).Conclusions: In the largest study to date examining readmissions after CRS-HIPEC, 30-day readmission rate was 15.9%. Tumor factors failed to predict readmission, whereas preoperative functional status and depression along with individual cytoreductive procedures predicted readmission. Patients with these risk factors or postoperative complications may benefit from closer post-discharge monitoring. [ABSTRACT FROM AUTHOR]

Background: Appendiceal adenocarcinoma with signet ring cells (SCA) is associated with worse overall survival (OS), and it is unclear whether cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) should be pursued in this patient population. We assessed the prognostic implications of signet ring cells in patients with appendiceal adenocarcinoma and peritoneal carcinomatosis undergoing CRS-HIPEC.Methods: The US HIPEC Collaborative, a 12-center, multi-institutional database of patients undergoing CRS-HIPEC, was reviewed for patients with SCA. Univariate and multivariate analyses were performed.Results: Of 514 patients undergoing CRS-HIPEC for appendiceal adenocarcinoma, 125 (24%) had SCA. The SCA and non-SCA groups had similar baseline characteristics. SCA had worse OS compared with non-SCA (32.0 vs 91.4 months, p < 0.001). In univariate analysis for only SCA cases, there was worse OS in patients with poorly differentiated tumors, positive lymph nodes, LVI, PCI > 20, or incomplete cytoreduction (CC-2/3). However, multivariate analysis showed only positive lymph nodes (HR 1.14 [95% CI 1.00-1.31], p = 0.04), poor differentiation (5.60 [1.29-24.39], p = 0.02), and incomplete cytoreduction (4.90 [1.11-12.70], p = 0.03) were independently associated with decreased OS for SCA.Conclusion: While signet cells are a negative prognostic feature, they should not be a contraindication to CRS-HIPEC in patients with well-moderately differentiated tumors with negative lymph nodes, where complete cytoreduction can be achieved. [ABSTRACT FROM AUTHOR]

Background: Liver transplantation (LT) is the preferred treatment for early hepatocellular carcinoma (HCC) in select patients. Differences in outcomes after LT have been previously described between recipient races, but the role of donor race is not well defined. This study sought to examine the effect of donor-recipient race-matching on overall survival after liver transplantation for HCC in African-American patients (AA).Study Design: Adult AA patients with HCC undergoing liver transplantation were identified using the Organ Procurement and Transplantation Network database (1994 to 2015). Recipient and donor demographic and clinical characteristics were collected. Patients were separated into unadjusted cohorts based on whether the liver donor was AA (matched) or another race (unmatched). The primary outcome was overall survival, which was analyzed by log-rank test and graphed using the Kaplan-Meier method. Multivariate regression modeling was used to determine adjusted hazard ratios (HR) for overall survival.Results: Of 1,384 AA patients identified, 325 (23.5%) were race-matched. Matched patients experienced significantly better median overall survival when compared with the unmatched cohort (135 vs 78 months, p = 0.007). Multivariate analysis revealed an adjusted hazard ratio of 0.66 for race-matched transplantation (95% CI 0.49 to 0.88; p = 0.004). Matched patients also experienced an improved 5-year survival (64.2% vs 56.9%; p = 0.019).Conclusions: African-American HCC patients undergoing liver transplantation experienced significantly improved overall survival when the donor race matched the recipient race. Donor-recipient race-matching remained an independent predictor of improved survival after adjusting for comorbidities and disease characteristics. Race-matching should be considered in the process of organ allocation because it may affect long-term survival in African-American HCC patients. [ABSTRACT FROM AUTHOR]

Background Transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) remains controversial. This systematic review sought to examine the role of TACE in the treatment of HCC with PVT in either the main portal vein (MPV) or portal vein branches (PVB). Methods PubMed was searched for “hepatocellular carcinoma” and “transarterial chemoembolization” from January 1, 2006 to August 31, 2016. Cohorts treated with TACE for HCC with PVT were included. Meta-analysis of overall survival (OS), mRECIST response, and complication incidence was performed. MPV and PVB subgroups were compared. Results Of 136 search results, 13 studies with 1933 TACE patients were included. Median OS (95% CI) was eight (5–15) months. Survival rates after one, three, and five years were 29% (20%–40%), 4% (1%–11%), and 1% (0%–5%), respectively. Only 1% experienced liver failure and 18% had post-treatment complications. Patients with MPV thrombosis had worse survival than PVB patients (p < 0.001), but similar mRECIST response rates (14% vs. 16%, p = 0.238). Conclusion TACE is a safe treatment for a highly selected population of HCC patients with PVT. Despite worse survival rates compared to PVB thrombosis, PVT in the MPV should not be considered an absolute contraindication to TACE. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to generate a map of local recurrences after neoadjuvant chemotherapy and radiation (total neoadjuvant therapy [TNT]) followed by surgical resection for pancreatic ductal adenocarcinoma (PDAC). Such recurrence patterns will serve to inform radiation treatment planning volumes that should be given in the neoadjuvant setting., Methods and Materials: Locoregional recurrences after TNT followed by surgery treated between 2009 and 2022 were radiologically identified. Recurrences were individually segmented using MIM software and complied in a single base scan. All contour compilations were used to create a threshold contour encompassing 80% of recurrences among all patients, head only, and body/tail only. The distance between organs at risk and the threshold contour were measured to design an optimal clinical target volume contour for patients treated with TNT. Recurrence patterns were also compared with existing adjuvant guidelines to assess coverage., Results: A database of 474 patients managed with TNT for PDAC was queried. While locoregional recurrences were rare in this cohort, we identified 80 patients with either isolated locoregional or simultaneous local and distant recurrences. Patients with diagnostic imaging at the time of recurrence were identified. The majority of recurrences were partially in the field of published contouring guidelines or volumetric expansions off of vessels, and volumetric coverage was low for all. Common areas of recurrence include the aorticodiaphragmatic junction, retropancreatic duodenal nodal basin, and the region to the right of the superior mesenteric artery. A novel set of proposed neoadjuvant contours was designed to cover the central-most 80% of recurrences., Conclusions: This is the largest collection of local/regional PDAC recurrences from a cohort of patients treated exclusively with TNT. Patterns of local/regional recurrence using TNT in PDAC vary significantly from those patients with PDAC treated with a surgery-first approach. Novel contouring guidelines presented in this study can help to ensure optimal coverage of high risk regions and avoid reliance on the current adjuvant guidelines to guide treatment planning., (Published by Elsevier Inc.)

Competing Interests: Conflicts of Interest and Source of Funding: None.