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Background: Merkel cell carcinoma (MCC) is a radiosensitive aggressive skin cancer that spreads via the lymphatics. There is uncertainty regarding the optimal management of the nodal basin for patients with MCC with clinically positive nodes. We study the efficacy of single node excision (SNE) as an alternative to a therapeutic lymph node dissection (TLND) in patients with limited nodal disease., Methods: We performed a retrospective cohort study of patients with MCC with clinical nodal disease who underwent resection in the form of either SNE or TLND using the National Cancer Database. The association between type of surgery and overall survival (OS) was estimated using the Kaplan-Meier method and Cox proportional hazards modeling., Results: 1835 patients met all inclusion criteria with 281 patients undergoing SNE and the remainder undergoing TLND. Patients receiving SNE and TLND were equally likely to receive radiation to the nodal basin (SNE 44.5% vs. TLND 48.5%, p = 0.22). There was no difference in 5-year OS between patients who received SNE versus TLND (SNE 43.9% vs. TLND 44.7%, p = 0.36). This persisted in a multivariable Cox proportional hazards model in which receipt of SNE remained not significantly associated with survival after adjusting for clinical and treatment factors including receipt of radiation (Hazard Ratio [HR] 1.17, 95% CI 0.96-1.42, p = 0.11). In patients undergoing SNE with radiation, 5-year OS was 54.4% (95% CI 44.1-63.6)., Conclusions: TLND is not associated with a survival advantage over SNE. Further prospective study into patterns of recurrence and safety of SNE is needed., (© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Introduction: We examined trends in major morbidity and mortality following total gastrectomy for malignancy in a national cohort., Methods: The National Surgical Quality Improvement Program was used to identify patients who underwent total gastrectomy for malignancy from 2007 to 2021. Joinpoint regression was used to determine annual percent changes (APCs) in thirty-day postoperative major morbidity, mortality, and length of stay (LOS). Major morbidity included deep and organ space surgical site infection, venous thromboembolism, cardiac event, pneumonia, acute renal failure, sepsis, and respiratory failure., Results: Of 3515 patients, the median age was 65 years (IQR = 55-73), 59% were male, and 57.9% were White. Major morbidity was 23%, which did not change over time (APC = -1.4, 95% CI = -3.4 to 0.58), nor were there changes in individual morbidities with time. The most common morbidities were organ space surgical site infection (9.2%) and pneumonia (8.5%). Mortality rate in the study cohort was 2.7% and did not change (APC = -6.2, 95% CI = -13.0 to 1.1). LOS (median 9 days) also did not vary with time (APC = -2.3, 95% CI = -7.8 to 3.9). There was an increase in patients with diabetes (21.6% vs. 11.2%, p < 0.05), BMI ≥ 30 (31.1% vs. 18.2%, p < 0.05), and ASA IV-V status (11.6% vs. 3.5%, p < 0.05)., Conclusion: Morbidity and mortality following total gastrectomy for malignancy have not significantly changed over the last fifteen years. While this may in part be explained by increased patient comorbidity, efforts should be made to improve patient selection and mitigate postoperative complications to allow for timely adjuvant therapies., (© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Background and Objectives: The impact of neoadjuvant immunotherapy (NIT) on overall survival (OS) in patients with resectable stage III melanoma remains unknown. We sought to identify factors associated with receipt of NIT and survival outcomes in patients with clinical stage III melanoma undergoing surgery., Methods: The National Cancer Database (2016-2020) was used to identify patients with clinical stage III melanoma who underwent surgery and received either NIT or adjuvant immunotherapy (AIT) only. Multivariable regression, Kaplan-Meier, and Cox proportional hazard methods were used to analyze variables of interest., Results: Patients with clinical N3 disease had 2.5 times the odds of NIT compared to those with N1 disease (95% CI 1.74-3.49). There was no difference in 3-year OS between the two cohorts: 79% (95% CI 73%-85%) for NIT patients and 75% (95% CI 73%-76%) for AIT patients (p = 0.078). Patients with N2/N3 disease had improved 3-year OS of 79% with NIT versus 71% for AIT-only (HR 0.61, 95% CI 0.38-0.97, p = 0.037)., Conclusions: NIT is given more selectively to clinical stage III patients with more advanced N category disease. Despite significant differences in N category between groups, there was no difference in OS observed at 3 years, and NIT was associated with a survival advantage among N2/N3 patients., (© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Background: Clinically localized Merkel cell carcinoma (MCC) is commonly treated with surgical excision and radiotherapy. The relationship between time to adjuvant radiotherapy and overall survival (OS) remains understudied., Methods: This retrospective study used data from the National Cancer Database (2006-2019). Patients with clinically localized MCC who received surgical excision and adjuvant radiotherapy were included. Multivariate regressions were used to account for various patient and tumor factors. The primary outcome was 5-year OS, and the secondary outcome was time from diagnosis to adjuvant radiation (TTR)., Results: Of the 1965 patients included, most were male (n = 1242, 63.2%) and white (n = 1915, 97.5%), and the median age was 74 years (interquartile range [IQR]: 66-81). The median TTR was 83 days (IQR: 65-106). A total of 83.6% of patients received radiotherapy to the primary site, 21.3% to the draining nodal basin, 17.1% to both, and 12.2% whose target location of radiotherapy was not recorded in the data. TTR of ≥79 days (the 45th percentile) was associated with worse OS on both univariate and multivariate analyses (log-rank p = 0.0014; hazard ratio [HR]: 1.258, 95% confidence interval [CI]: 1.055-1.500, p = 0.010). This persisted on sub-analyses of patients <80 years old (n = 1407; HR: 1.380, 95% CI: 1.080-1.764, p = 0.010) and of patients with Charlson comorbidity index (CCI) of 0 (n = 1411; HR: 1.284, 95% CI: 1.034-1.595, p = 0.024). Factors associated with delayed TTR included greater age (p = 0.039), male sex (p = 0.04), CCI > 1 (p = 0.036), academic facility (p < 0.001), rural county (p = 0.034), AJCC T2 stage (p = 0.010), negative margins (p = 0.017), 2+ pathologically positive regional nodes (p = 0.011), and margin size >2 cm (p = 0.015)., Conclusions: Delayed radiotherapy (≥79 days) was associated with worse OS of MCC patients. Further study in controlled cohorts is needed to ascertain this relationship., (© 2023 Wiley Periodicals LLC.)

Introduction: Many patients with high-risk soft tissue sarcoma (STS) develop distant metastases. Meta-analyses suggest that chemotherapy confers a small survival benefit, though few studies focus on neoadjuvant chemotherapy (NCT). There has been more frequent use of neoadjuvant radiation therapy (NRT) in STS, but the utility of NCT for these patients remains unclear., Methods: Patients with stage II-III trunk/extremity STS who underwent NRT and resection were identified using the National Cancer Database (2006-2019). Predictors of NCT were analyzed using logistic regression. Change in rate of NCT use over time was assessed using log-linear regression modeling. Survival was examined using Kaplan-Meier (KM) and Cox proportional hazard modeling., Results: Of 5740 patients, 25% underwent NCT. The overall median age was 62, 55% of patients were male, and 67% had stage III disease. The most common histological subtypes were fibrosarcoma/myxofibrosarcoma (39%) and liposarcoma (16%). Use of NCT decreased by 4.0% per year throughout the study period (p < 0.01). Predictors of NCT included younger age (median 54, IQR 42-64 vs. median 65, IQR 53-75, p < 0.01), treatment at an academic center (odds ratio [OR] 1.5, p < 0.01), and stage III disease (OR 2.2, p < 0.01). Histologic predictors of NCT included synovial sarcoma (52%) and angiosarcoma (45%). With a median follow-up time of 77 months, NCT was associated with improved 5-year survival compared to NRT alone on KM analysis (70% vs. 63%, p < 0.01). This difference persisted on multivariate analysis (hazard ratio 0.86, p = 0.027) and after propensity matching (70% vs. 65%, p = 0.0064)., Conclusion: Despite risk of distant failure in high-risk STS, use of NCT has decreased over time in patients receiving NRT. In this retrospective analysis, NCT was associated with a modestly improved overall survival., (© 2023 Wiley Periodicals LLC.)

Background and Objectives: We aim to assess the quality and readability of online information available to patients considering cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC)., Methods: The top three search engines (Google, Bing, and Yahoo) were searched in March 2022. Websites were classified as academic, hospital-affiliated, foundation/advocacy, commercial, or unspecified. Quality of information was assessed using the JAMA benchmark criteria (0-4) and DISCERN tool (16-80), and the presence of a Health On the Net code (HONcode) seal. Readability was evaluated using the Flesch Reading Ease score., Results: Fifty unique websites were included. The average JAMA and DISCERN scores of all websites were 0.72 ± 1.14 and 39.58 ± 13.71, respectively. Foundation/advocacy websites had significantly higher JAMA mean score than commercial (p = 0.044), academic (p < 0.001), and hospital-affiliated websites (p = 0.001). Foundation/advocacy sites had a significantly higher DISCERN mean score than hospital-affiliated (p = 0.035) and academic websites (p = 0.030). The HONcode seal was present in 4 (8%) websites analyzed. Readability was difficult and at the level of college students., Conclusions: The overall quality of patient-oriented online information on CRS-HIPEC is poor and available resources may not be comprehensible to the general public. Patients seeking information on CRS-HIPEC should be directed to sites affiliated with foundation/advocacy organizations., (© 2022 Wiley Periodicals LLC.)

Background and Objectives: Type II diabetes mellitus (T2DM) can lead to an immunosuppressed state, but whether T2DM is associated with worse outcomes for patients with melanoma has not been well studied., Methods: Consecutive patients diagnosed with clinical stage I-II cutaneous melanoma who underwent sentinel lymph node biopsy at a single institution (2007-2016) were identified. Melanoma characteristics and recurrence/survival outcomes were compared between patients with and without T2DM at the time of melanoma diagnosis., Results: Of 1128 patients evaluated, 111 (9.8%) had T2DM (n = 94 [84.7%] non-insulin dependent [NID-T2DM]; n = 17 [15.3%] insulin dependent [ID-T2DM]). T2DM patients were more likely to be older (odds ratio [OR] 1.04, p < 0.001), male (OR 2.15, p = 0.003), have tumors >1.0 mm (OR 1.88, p = 0.023), and have microsatellitosis (OR 2.29, p = 0.030). Five-year cumulative incidence of melanoma recurrence was significantly higher for patients with ID-T2DM (46.7% ID-T2DM vs. 25.7% NID-T2DM vs. 17.1% no T2DM, p < 0.001), and on multivariable analysis, ID-T2DM was independently associated with melanoma recurrence (hazard ratio 2.57, p = 0.015). No difference in 5-year disease-specific survival was observed between groups., Conclusions: ID-T2DM appears to be associated with more advanced melanoma and increased risk for melanoma recurrence. Further study as to whether this reflects differences in tumor biology or host factors is warranted., (© 2022 Wiley Periodicals LLC.)

Background and Objectives: Medicaid expansion has improved healthcare coverage and preventive health service use. To what extent this has resulted in earlier stage colorectal cancer diagnoses and impacted perioperative outcomes is unclear., Methods: This was a retrospective difference-in-difference study using the National Cancer Database on adults (40-64) with Medicaid or no insurance, diagnosed with colorectal adenocarcinomas before (2010-2013) and after (2015-2018) expansion. The primary outcome was early-stage (American Joint Committee on Cancer Stage 0-1) diagnosis. The secondary outcomes were rate of local excision, emergency surgery, postoperative length of stay, rates of minimally invasive surgery, postoperative mortality, and overall survival (OS)., Results: Medicaid expansion was associated with an increase in early-stage diagnoses for patients with colorectal cancers (odds ratio [OR]: 1.28, 95% confidence interval [CI]: 1.15-1.43), an increase in local excision (OR: 1.39, 95% CI: 1.13-1.69), and a decreased rate of emergent surgery (OR: 0.85, 95% CI: 0.75-0.97) and 90-day mortality (OR: 0.75, 95% CI: 0.59-0.97). Additionally, patients in expansion states postexpansion had an improved 5-year OS (hazard ratio: 0.88, 95% CI: 0.83-0.94)., Conclusions: Insurance coverage expansion may be particularly important for optimizing stage of diagnosis, subsequent survival, and perioperative outcomes for socioeconomically vulnerable patients., (© 2022 Wiley Periodicals LLC.)

Background: We sought to identify factors associated with 30-day morbidity, and their impact on 30-day mortality, among patients undergoing splenectomy for immune thrombocytopenic purpura (ITP)., Methods: Using the ACS-NSQIP database, patients undergoing splenectomy for ITP were identified (2005-2019), and those with and without postoperative complications within 30 days of surgery were compared., Results: Of 2483 patients evaluated, 280 (11.3%) developed 30-day morbidity: infection (n= 145 [5.8%]), venous thromboembolism (n = 71 [2.9%]), acute renal failure (n = 7 [0.3%]), respiratory failure (n = 40 [1.6%]), cardiac arrest/myocardial infarction (n = 16 [0.6%]), cerebrovascular accident (n = 4 [0.2%]), or postoperative blood transfusion (n = 62 [2.5%]). Risk-factors for 30-day morbidity included age ≥50 years (odds ratio [OR] 1.50, p = 0.020), body mass index ≥30 kg/m 2 (OR 1.45, p = 0.023), functional dependence (OR 2.90, p = 0.009), preoperative albumin <3.5 g/dL (OR 2.10, p < 0.001), preoperative platelets <30 000/μL (OR 1.54, p = 0.020), open surgical approach (OR 2.32, p < 0.001), and inpatient status before surgery (OR 1.85, p = 0.040). Among patients at low-risk for 30-day morbidity (no risk-factors present), the 30-day morbidity rate was 5.0% versus 41.5% for ≥5 risk-factors (p < 0.001). Thirty-day mortality was 1.2%., Conclusions: Thirty-day morbidity and mortality are low with splenectomy for ITP. Select patients have particularly low perioperative risk and may benefit from early splenectomy if initial medical therapy fails., (© 2022 Wiley Periodicals LLC.)

Background and Objectives: Conditional survival (CS) analysis has emerged as a dynamic prognostication methodology. The goal of this study was to determine disease-specific CS rates in Merkel cell carcinoma (MCC)., Methods: This retrospective study included patients with MCC from the Surveillance Epidemiology and End Results (SEER) registry (1988-2016). Stage-specific 5-year MCC-specific CS rates for study and survivor cohorts were estimated, and the significance of clinicopathologic factors to predict 1-year MCC-specific death was evaluated using multivariate logistic regression., Results: Within stage, 5-year CS survival rates improved with increasing survivorship. Pathologic Stage I patients had the highest 5-year CS rate at diagnosis (89.1%) but the smallest increase over time (96% among 5-year survivors). Stage IV patients experienced the greatest change in 5-year CS rates from 25.4% (at diagnosis) to 88% (5-year survivors). At diagnosis stage, age, sex, and primary site were all significantly associated with 1-year MCC-related death in the multivariate analysis. In contrast, among 5-year survivors only sex and age at diagnosis were significant predictors., Conclusions: MCC CS rates improved across all disease stages over time. Additionally, the relationships of prognostic factors with 1-year MCC-death changed with increasing survivorship. This perspective can provide a foundation for informed decision-making., (© 2022 Wiley Periodicals LLC.)

Background: Although high volume centers (HVC) equate to improved outcomes in rectal cancer, the impact of surgical volume related to race is less defined., Methods: Patients who underwent surgical resection for stage I-III rectal adenocarcinoma were divided into cohorts based on race and hospital surgical volume. Outcomes were analyzed following 1:1 propensity-score matching using logistic, Poisson, and Cox regression analyses with marginal effects., Results: Fifty-four thousand one hundred and eighty-four (91.5%) non-Black and 5043 (8.5%) Black patients underwent resection of rectal cancer. Following 1:1 matching of non-Black (N = 5026) and Black patients, 5-year overall survival (OS) of Black patients was worse (72% vs. 74.4%, average marginal effects [AME] 0.66, p = 0.04) than non-Black patients. When compared to non-Black patients managed at HVCs, Black patients had worse OS (70.1% vs. 74.7%, AME 1.55, p = 0.03), but this difference was not significant when comparing OS between non-Black and Black patients managed at HVCs (72.3% vs. 74.7%, AME 0.62, p = 0.06). Length of stay was longer among Black and HVC patients across all cohorts. There was no difference across cohorts in 90-day mortality., Conclusions: Although racial disparities exist in rectal cancer, this disparity appears to be ameliorated when patients are managed at HVCs., (© 2021 Wiley Periodicals LLC.)

Background and Objectives: Neoadjuvant radiation (NRT) is frequently utilized in soft tissue sarcomas to increase local control. Its utility in cutaneous and soft tissue angiosarcoma remains poorly defined., Methods: This retrospective cohort study was performed using the National Cancer Database (2004-2016) evaluating patients with clinically localized, surgically resected angiosarcomas. Factors associated with receipt of NRT in the overall cohort and margin positivity in treatment naïve patients were identified by univariate and multivariable logistic regression analyses. Survival was assessed using Kaplan-Meier analysis., Results: Of 597 patients, 27 (4.5%) received NRT. Increasing age (odds ratio [OR] 0.95, p = 0.025), tumor size more than or equal to 5 cm (OR 3.16, p = 0.02), and extremity tumor location (OR 3.99, p = 0.04) were associated with receipt of NRT. All patients who received NRT achieved an R0 resection (p = 0.03) compared with 17.9% of patients without NRT. Factors associated with risk of margin positivity included tumor size more than or equal to 5 cm (OR 1.85, p = 0.01), and head/neck location (OR 2.24, p = 0.006). NRT was not significantly associated with improved survival (p = 0.21)., Conclusions: NRT improves rates of R0 resection but is infrequently utilized in cutaneous and soft tissue angiosarcoma. Increased usage of NRT, particularly for patients with lesions more than or equal to 5 cm, or head and neck location, may help achieve complete resections., (© 2021 Wiley Periodicals LLC.)

Background: Rates of nonoperative management of acute appendicitis and appendiceal adenocarcinoma have increased over a decade, but the presentation and outcomes of appendiceal adenocarcinoma over this period is not well-characterized., Methods: Patients with surgically resected Stage I-III appendiceal adenocarcinoma were identified from the 2006 to 2015 National Cancer Data Base and classified into two cohorts, 2006-2010 and 2011-2015, based on year of diagnosis. Three-year overall survival (OS) was analyzed using Cox proportional hazards regression and Kaplan-Meier survival estimates., Results: Of 4233 patients, 1369 (32.3%) and 2864 (67.7%) were diagnosed in 2006-2010 and 2011-2015, respectively. Following multivariable analysis, patients in 2011-2015 were more likely to be <40 years of age (6.4% vs. 4.7%, odds ratio [OR] 1.53, p .015), present with pT4 tumors (40.2% vs. 34.4%, OR 1.46, p .004), and undergo hyperthermic intraperitoneal chemotherapy (4.4% vs. 2.4%, OR 1.97, p .001). Comparing patients diagnosed in 2011-2015 to 2006-2010, adjusted 3-year OS was no different among all patients (81.1% vs. 79%, p .778)., Conclusions: There has been an increase in the proportion of patients with pT4 appendix tumors over time, primarily among older (≥60 years) patients. Even so, these shifts in presentation have not resulted in differences in survival outcomes., (© 2020 Wiley Periodicals LLC.)

Background: Regionalization of oncologic care has increased, but less is known whether patient outcomes are influenced by receipt of multimodality care through multicenter care (MCC) or single-center care (SCC)., Methods: Patients from 2004 to 2015 National Cancer Data Base diagnosed with stage II-III esophageal (EA), stage II-III pancreatic (PA), and stage II-IV rectal (RA) adenocarcinoma who underwent resection at a high volume center (HVC) and required radiation and/or chemotherapy were included. MCC (care at 2+ facilities) and SCC patients were propensity-score matched 1:2 and Cox proportional hazards regression used to analyze survival., Results: On multivariable regression analysis, MCC in RA patients (N = 325/2097, 15.5%) was more associated with residing ≥40 miles from the HVC (odds ratio [OR] = 2.37; P = .044) and receipt of neoadjuvant chemotherapy (1.42, P = .040). In PA patients (N = 75/380, 19.7%), residing ≥40 miles from the HVC (OR = 3.22; P = .001), and in EA patients (N = 88/534, 16.5%), younger patients (<50 years: OR = 2.96; P = .011) were associated with MCC. Following propensity score matching, EA (N = 147), PA (N = 133), and RA (N = 661) patients had no difference in 1-year and 3-year overall survival when comparing MCC to SCC., Conclusions: The use of MCC appears safe without a difference in survival and may offer significant advantages in convenience to patients as they undergo their complex oncologic care., (© 2020 Wiley Periodicals LLC.)

Background and Objectives: Hepatocellular carcinoma (HCC) patients are often not candidates for resection. This study hypothesized that external beam radiation (XRT) could be equally effective compared to ablation therapy (AT) for selected HCC patients., Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify HCC patients (2004-2012) undergoing XRT or AT for solitary HCC lesions. Propensity score modeling was utilized to adjust for baseline characteristics., Results: Propensity matching identified 784 patients: 157 (20%) XRT and 627 (80%) AT. Median OS for XRT and AT was 22, and 32 months (P < 0.001), respectively. AT demonstrated improved OS for tumors 3-5 cm (30 vs 16 m, P < 0.001) and >5 cm (25 vs 9 m, P < 0.001). Similar survival was found in patients with tumor size <3 cm (37 vs 47 m P = 0.508). Following multivariate analyses, XRT was associated with an increased hazard ratio (HR = 1.64, P < 0.001). Elevated AFP at diagnosis (HR = 1.54, P = 0.001) and tumor size >3 were identified as negative predictors of survival., Conclusions: Similar survival for solitary HCC lesions <3 cm exists between XRT and AT. However, AT demonstrates improved survival rates compared to XRT for lesions >3 cm. This 3 cm reference point may serve as a valuable metric to guide treatment decisions and future investigations., (© 2017 Wiley Periodicals, Inc.)

Background and Objectives: The multi-modal treatment of retroperitoneal sarcoma has seen increased use of neoadjuvant radiation. However, its effect on local recurrence and survival remain controversial. We aimed to synthesize and evaluate the literature., Methods: The review was conducted according the recommendation of the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) group with pre-specified inclusion and exclusion criteria., Results: Of 8,701 citations collected, 15 articles reported on 464 patients. The median age was 56 years (45-64). The predominant histological subtypes were liposarcoma (51.54%) and leiomyosarcoma (23.26%). Tumor differentiation composed of 37.1% well-, 12.8% moderate-, 46.0% poorly-, and 4.1% undifferentiated. Most studies featured external beam radiation therapy (EBRT) treatment regimen with some who included patients treated with IMRT instead. Median follow-up averaged 41.4 months (19-106 months). Median 5-year OS, PFS, and LRR rates were 58%, 71.5%, and 25%. Using the NCI CTCAE, toxicities from Grade 1 (Mild) through Grade 5 (death) were experienced by 18.8%, 10.2%, 16.3%, 0.7%, and 1.6% of patients., Conclusions: NART is a safe to use for RPS, but its effect toward survival and local control remains unclear. Without randomized control trials, common reporting criteria for pro- and retrospective studies are needed to allow comparison between studies. J. Surg. Oncol. 2016;113:628-634. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background and Objectives: Effective therapies for hepatocellular carcinoma (HCC) are limited. Molecular profiling of HCC was performed to identify novel therapeutic targets., Methods: 350 HCC samples were evaluated using a multiplatform profiling service (Caris Life Sciences, Phoenix, AZ), including gene sequencing, amplification, and protein expression., Results: EGFR, TOPO1, PD-1, TOP2A, SPARC, and c-Met were overexpressed in 25-83% of samples. Decreased expression of RRM1,TS, PTEN, and MGMT occurred in 31-82% of samples. TP53 was mutated in 30%, CTNNB1 in 20%, and BRCA2 in 18%; other gene mutation rates were <5%. TP53-mutated tumors showed significantly higher TOPO2A (90% vs. 38%, P < 0.0001) and TS (56% vs. 29%, P = 0.0139) expression. CTNNB1-mutated tumors had significantly higher AR (56% vs. 21%, P = 0.0017), SPARC (61% vs. 29%, P = 0.0135), PDL1 (29% vs. 0%, P = 0.0256) expression, and BRCA2 mutations (50% vs. 6%, P = 0.0458). Metastases exhibited significantly higher infiltration by PD-1+ lymphocytes (79% vs. 50%, P = 0.047) and TS (31% vs. 14%, P < 0.0003) than primary HCC., Conclusions: Multiplatform profiling reveals molecular heterogeneity in HCC and identifies potential therapies including tyrosine kinase, PI3 kinase, or PARP inhibitors for molecular subtypes. Chemotherapy may benefit some tumors. CTNNB1-mutated tumors may respond to multi-target inhibition. These limited and preliminary data require clinical validation., (© 2015 Wiley Periodicals, Inc.)

Background: Hepatic artery based therapies (HAT) are offered for patients with unresectable intrahepatic cholangiocarcinoma (ICC). We aimed to evaluate the comparative effectiveness of HAT -hepatic arterial infusion (HAI), transcatheter arterial chemoembolization (TACE), drug-eluting bead TACE (DEB-TACE), and Yttrium(90) radioembolization (Y-90) for unresectable ICC., Methods: A meta-analysis was performed using a prospectively registered search strategy at PROSPERO (CRD42013004830) that utilized PubMed (2003-2013). Primary outcome was median overall survival (OS), and secondary outcomes were tumor response to therapy and toxicity., Results: A total of 20 articles (of 793, n=657 patients) were selected for data extraction. Highest Median OS was observed for HAI (22.8, 95% CI 9.8-35.8) months versus Y90 (13.9, 9.5-18.3) months versus TACE (12.4, 10.9-13.9) months versus DEB-TACE (12.3, 11-13.5) months. Response to therapy (complete and partial) was highest for HAI (56.9%, 95%CI 41.0-72.8) versus Y90 (27.4%, 17.4-37.5) versus TACE (17.3%, 6.8-27.8). The grade III/IV toxicity (Events per patient) was highest for HAI (0.35, 95% CI 0.22-0.48) versus TACE (0.26, 0.21-0.32) versus DEB-TACE (0.32, 0.17-0.48)., Conclusion: For patients with unresectable ICC treated with HAT, HAI offered the best outcomes in terms of tumor response and survival but may be limited by toxicity., (© 2014 Wiley Periodicals, Inc.)

Background and Objectives: Fibrolamellar carcinoma (FLC) presents in young, otherwise-healthy individuals. This study examined recurrence and survival characteristics after surgical resection for FLC by utilizing an international multi-institutional database., Methods: Consecutive patients undergoing hepatectomy for FLC from six institutions (1993-2010) were reviewed retrospectively. Survival was studied with life tables and Cox regression models., Results: Thirty-five patients (13 female, 37%) were included (median age: 32 years). R0 resection was achieved in all curative-intent operations (n = 30), and palliative operations were performed for five patients. Crude 30-day morbidity and mortality rates were 22% and 3%, respectively. For curative-intent surgery, overall and recurrence-free survivals at 5 years were 62% and 45%, respectively. In patients who achieved a 4-year disease-free interval after surgery, none subsequently developed recurrence. In multivariate models, presence of extrahepatic disease was the only factor that independently predicted overall (hazard ratio [HR]: 5.58, 95% confidence interval [CI]: 1.38-22.55, P = 0.016) and recurrence-free survival (HR: 5.64, 95% CI: 1.48-21.49, P = 0.011)., Conclusions: Patients with surgically amenable FLC had encouraging long-term survival. Recurrence-free survival to 4 years suggested possible freedom from disease thereafter. Recurrent resectable disease was associated with an excellent prognosis, and repeat surgery should be strongly considered., (© 2014 Wiley Periodicals, Inc.)

Background and Objectives: Current NCCN guidelines recommend epirubicin (E), cisplatin (C), and 5-fluorouracil (F) as a first-line therapeutic approach for operable gastric adenocarcinoma (GC). Molecular profiling (MP) was used to evaluate the expression of chemotherapy targeted biomarkers associated with ECF therapy and other first-line cytotoxic regimens for GC., Methods: GC specimens were analyzed by immunohistochemistry (IHC) for TOP2A, TS, ERCC1, PGP, and TOPO1 expression (Caris Life Sciences, Phoenix, AZ) from 2009 to 2012., Results: A total of 230 GC specimens were analyzed. The median age of patients was 61 (IQR: 50-72) years with the majority being male (n = 139, 60%). IHC actionable targets included: 60% (n = 138) high TOP2A, 55% (n = 127) negative ERCC1, and 63% (n = 145) negative TS, indicating potential benefit from E, C, and F, respectively. Simultaneous expression analysis demonstrated only 24% (n = 55) of patients had gene expression levels that suggested uniform sensitivity to ECF. Biomarker results of 6.5% (n = 15) of patients revealed a potential complete lack of sensitivity to first-line ECF., Conclusions: MP of GC has the potential to define patients who would derive the greatest benefit from current therapies. Prospective controlled studies are required to validate the role of biomarkers in the management of GC patients., (© 2014 Wiley Periodicals, Inc.)

Background and Objectives: Malignant vascular tumors (MVT) of the liver are uncommon and poorly understood. We hypothesized that tumor histology is a predominant factor associated with survival in these tumors., Methods: Patients with malignant histopathologic diagnoses of hepatic angiosarcoma (AS), hemangioendothelioma (HE) and its epithelioid variant (EHE), or hemangiopericytoma (HP) were identified using the SEER database (1973-2007). Overall survival (OS) was studied with Kaplan-Meier curves., Results: We included 297 patients with MVT (207 AS, 28 HE, 56 EHE, 6 HP). All tumors demonstrated metastatic potential, although EHE and AS had the highest rate of regional or distant metastases (75% each). Patients with AS had the shortest median OS (1 month), however, those undergoing surgery had improved survival (6 months). Three patients with AS underwent liver transplant and lived for 11, 21, and 91 months each. Patients with EHE had the longest overall median survival of 75 months (30-183, P < 0.001). Surgical resection and transplant did not demonstrate an improvement in OS of patients with EHE in multivariable models., Conclusions: Histology is an important factor in determining survival for patients with hepatic MVT. Patients with EHE have the longest OS, whereas patients with AS have shorter survival but may benefit from surgery., (© 2013 Wiley Periodicals, Inc.)