Perioperative therapy in metastatic colorectal cancer: Pattern of use and survival outcomes.

BACKGROUND: Multimodality therapy of metastatic colorectal cancer (mCRC) is currently considered the standard of care. The aim of this study was to evaluate the impact of perioperative therapy on surgical resection in mCRC. METHODS: The National Cancer Database was analyzed for affected patients between 2004 and 2013. Univariate and multivariate analyses were done to identify factors associated with patient outcomes. Kaplan-Meier analysis and Cox proportional hazards models were used for the association between patient characteristics and survival. RESULTS: About 61,940 patients with mCRC were identified. Mean age = 63.4 years (SD ± 14). About 69% had a colon primary and 32% had only one metastatic site. Only 49% of those who underwent surgery for both primary and metastatic sites received postoperative chemotherapy (p < .001). Negative prognostic factors included no chemotherapy received (hazard ratio [HR], 2.32; 2.27-2.37; p < .001), more than three metastatic sites (HR, 2.28; 2.09-2.48; p < .001), year of diagnosis between 2004 and 2008 (HR, 1.71; 1.15-1.20; p < .001) and colon tumor location with right worse than left-sided (HR, 1.21; 1.19-1.24; p < .001). Five-year overall survival for resection of the primary and metastatic site (28.2%) was higher than for no surgical treatment (4.7%). CONCLUSION: Perioperative therapy was associated with improved survival, following resection of metastatic sites or primary tumor.

Potential Biomarkers in Atrial Fibrillation: Insight Into Their Clinical Significance.

ABSTRACT: In risk-stratifying patients with atrial fibrillation (AF), physicians rely heavily on clinical parameters that provide risk scores and determine treatment strategies. There has been increasing research on potential biomarkers in the blood that could more accurately determine both risk of complications in AF and risk of incidence of AF. This review highlights the clinical significance of 5 novel biomarkers that have been shown to be linked to AF. These biomarkers are carbohydrate antigen 125, galectin-3, growth differentiation factor-15, a member of the interleukin 1 receptor family, IL1RL1 (ST2), and N-terminal pro B-type natriuretic peptide.

Survival outcome of adjuvant chemotherapy in deficient mismatch repair stage III colon cancer.

BACKGROUND: The prognostic impact of DNA mismatch repair (MMR) status remains controversial in patients with stage III colon cancer who are treated with adjuvant chemotherapy (AC). The aim of this study was to evaluate the survival outcome of AC in deficient mismatch repair (dMMR)/microsatellite instable (MSI) stage III CC. METHODS: Patients with pathological stage III CC between 2010 and 2013 were identified from the National Cancer Database using International Classification of Diseases for Oncology (3rd Edition) morphology and topography codes 8140, 8480, and C18.0-18.8. Patients with pathologic stage T3N2, T4N1, or T4N were considered high risk; patients with stage T3N1 were considered low risk. Univariate and multivariable analyses were conducted, and Kaplan-Meier analysis and Cox proportional hazards models were used to identify the association between AC and overall survival (OS). RESULTS: A total of 9226 patients with pathological stage III CC were identified, of which 2384 (25.8%) were MSI-high (MSI-H) and met the inclusion criteria of the final analysis. MSI-low (MSI-L) patients (n = 6842) were excluded. There was a preponderance of women (55.0% [n = 1311]), and 76.6% (n = 1825) of patients were non-Hispanic white. The median age was 65 years (range, 19-90 years). The primary sites were the cecum (29.7% [n = 707]), ascending colon (26.0% [n = 620]), sigmoid colon (17.2% [n = 410]), and transverse colon (10.8% [n = 257]). The most common tumor grade was moderately differentiated (n = 50.4% [1202]), followed by poorly differentiated (34.1% [n = 813]) and well differentiated (5.1% [n = 121]). High-risk pathologic stage III CC (T4N1, TxN2) constituted 51.0% (n = 1215) of the study population. High-risk stage III was associated with worse OS compared with low-risk stage III on univariate (P < .001) analysis and displayed a similar trend on multivariable analysis, without a statistically significant difference. Multiagent AC was associated with improved OS compared with no treatment on univariate (P < .001) and multivariable (P < .001) analysis. When stratified by risk status, multiagent AC was associated with improved OS compared with no treatment for high-risk (P < .001) and low-risk (P < .001) stage III disease. CONCLUSION: Adjuvant chemotherapy is associated with better OS in stage III dMMR/MSI-H CC. An enhanced benefit was shown for high-risk stage III disease.

Blood-Based Next-Generation Sequencing Analysis of Appendiceal Cancers.

BACKGROUND: Appendiceal cancers (ACs) are rare. The genomic landscape of ACs has not been well studied. The aim of this study was to confirm the feasibility of next-generation sequencing (NGS) using circulating tumor DNA (ctDNA) in ACs and characterize common genomic alterations. MATERIALS AND METHODS: Molecular alterations in 372 plasma samples from 303 patients with AC using clinical-grade NGS of ctDNA (Guardant360) across multiple institutions were evaluated. Test detects single nucleotide variants in 54-73 genes, copy number amplifications, fusions, and indels in selected genes. RESULTS: A total of 303 patients with AC were evaluated, of which 169 (56%) were female. Median age was 56.8 (25-83) years. ctDNA NGS testing was performed on 372 plasma samples; 48 patients had testing performed twice, 9 patients had testing performed three times, and 1 patient had testing performed four times. Genomic alterations were defined in 207 (n = 207/372, 55.6%) samples, and 288 alterations were identified excluding variants of uncertain significance and synonymous mutations. Alterations were identified in at least one sample from 184 patients; TP53-associated genes (n = 71, 38.6%), KRAS (n = 33, 17.9%), APC (n = 14, 7.6%), EGFR (n = 12, 6.5%), BRAF (n = 11, 5.9%), NF1 (n = 10, 5.4%), MYC (n = 9, 4.9%), GNAS (n = 8, 4.3%), MET (n = 6, 3.3%), PIK3CA (n = 5, 2.7%), and ATM (n = 5, 2.7%). Other low-frequency but clinically relevant genomic alterations were as follows: AR (n = 4, 2.2%), TERT (n = 4, 2.2%), ERBB2 (n = 4, 2.2%), SMAD4 (n = 3, 1.6%), CDK4 (n = 2, 1.1%), NRAS (n = 2, 1.1%), FGFR1 (n = 2, 1.1%), FGFR2 (n = 2, 1.1%), PTEN (n = 2, 1.1%), RB1 (n = 2, 1.1%), and CDK6, CDKN2A, BRCA1, BRCA2, JAK2, IDH2, MAPK, NTRK1, CDH1, ARID1A, and PDGFRA (n = 1, 0.5%). CONCLUSION: Evaluation of ctDNA is feasible among patients with AC. The frequency of genomic alterations is similar to that previously reported in tissue NGS. Liquid biopsies are not invasive and can provide personalized options for targeted therapies in patients with AC. IMPLICATIONS FOR PRACTICE: The complexity of appendiceal cancer and its unique genomic characteristics suggest that customized combination therapy may be required for many patients. Theoretically, as more oncogenic pathways are discovered and more targeted therapies are approved, customized treatment based on the patient's unique molecular profile will lead to personalized care and improve patient outcomes. Liquid biopsies are noninvasive, cost-effective, and promising methods that provide patients with access to personalized treatment.

Clinicopathological features and survival outcomes of rare histologic variants of gallbladder cancer.

BACKGROUND: Adenocarcinoma (AC) is the most common histological type in gallbladder carcinoma (GBC). Squamous cell carcinoma (SCC), adenosquamous carcinoma (ASC), and papillary carcinoma (PC) are rare histologic variants of GBC. METHODS: Patients with AC, SCC, ASC, and PC of the gallbladder between 2004 and 2013 were identified from the National Cancer Database. Univariate and multivariate analyses were performed, and Kaplan-Meier curves were used to compare overall survival (OS) based on histological subtype. RESULTS: A total of 5956 patients ≥18 years of age were included in the final analysis. Most patients (n = 5398; 90.6%) had AC compared with variant histologies. PC (n = 227; 3.8%) was the most common variant, followed by ASC (n = 216; 3.6%) and SCC (n = 115; 1.9%); 70.3% were female and 78.9% Caucasian. The median age was 70 (range, 25-90) years. Surgical resection was performed in 77.7% of AC, 53.0% of SCC, 88.9% of ASC, and 96.9% of PC (P < .001). Systemic therapy after surgery was administered in 25.1% of AC, 18.3% of SCC, 35.7% of ASC, and 19.4% of PC (P = .001). In multivariate analysis, multiagent chemotherapy was associated with improved OS in all histologies except for SCC and PC (p < .001), and adjuvant systemic therapy was associated with improved OS in ASC and AC (P < .001). CONCLUSION: Survival differs between the gallbladder variants. Except for SCC, GBC variants underwent surgical resection more often than AC. Adjuvant systemic therapy was associated with improved OS in ASC and AC.

Inhibition of HSP90 overcomes resistance to chemotherapy and radiotherapy in pancreatic cancer.

Resistance of pancreatic ductal adenocarcinoma (PDAC) to radiotherapy and chemotherapy represents a significant clinical issue. Although the mechanisms of resistance are multi-faceted, client proteins of heat shock protein 90 (HSP90) such as hypoxia induced factor-1α (HIF-1α) have a central role in this process. The purpose of this investigation was to evaluate inhibition of HSP90 as a therapeutic strategy for radiosensitization in pancreatic cancer. Ganetespib, a selective inhibitor of HSP90, was evaluated as a radio-sensitizer in setting of PDAC. Inhibition of HSP90 by ganetespib potentiated the ability of radiation therapy to limit cell proliferation and colony formation in vitro. HIF-1α expression was upregulated by irradiation and HIF-1α-overexpressing stable cell lines were resistant to radiation. Inhibition of HSP90 with ganetespib reversed the effects of HIF-1α overexpression, by reducing signaling via proliferative, angiogenic and anti-apoptotic pathways. The potentiation of the antitumor effects of chemoradiotherapy by ganetespib and modulation of key pathways (e.g. HIF-1α, STAT3, and AKT) was confirmed in vivo in nude mice bearing HPAC xenograft tumors. These novel data highlight HIF-1α-mediated mechanisms of HSP90 inhibition that sensitize PDAC cells to chemoradiotherapy. This pathway and its pleiotropic effects warrant further evaluation in concert with conventional therapy in pancreatic cancer clinical trials.

A pilot study of the immune microenvironment of GI neuroendocrine carcinoma.

Gastroenteropancreatic high-grade (HG) neuroendocrine carcinoma (GEP-NEC) is an aggressive malignancy with limited treatment options and increasing incidence in the United States. Due to the rarity of the cancer and heterogeneity of the primary tumor location, data on GEP-NEC oncogenesis and its interaction with the host immune system are limited. A greater understanding of GEP-NEC and its tumor microenvironment (TME) would benefit efforts to develop more effective targeted therapies and rationally adapt immunotherapy to this disease. In this study, we profiled the expression of 770 unique genes using 21 biopsy samples from patients with GEP-NEC using the NanoString nCounter PanCancer IO 360 platform. Our results show several trends evident within the GEP-NEC TME. Greater expression of genes indicative of immune cell infiltration was present within the TME of patients <60 years of age and in patients with greater overall survival (OS). Tumors from patients with non-pancreatic NEC had diminished MHCII expression compared to pancreatic NEC, suggesting more prominent adaptive immune responses in the pancreatic GEP-NEC subtype. Patients with a >6 months OS had tumors with elevated NK cell gene signatures compared to patients with poor survival. Further, the analysis revealed numerous differentially expressed genes based on patient age, tumor location, response to treatment, and OS, which warrant future validation for assessing the relationship with clinical outcomes in patients.

Survival and Prognostic Factors in Patients With Pancreatic Colloid Carcinoma Compared With Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: Colloid carcinoma (CC) is a rare subtype of pancreatic carcinoma. The aims of the study are to characterize the clinicopathological features and to evaluate the overall survival (OS) of patients with CC. METHODS: Patients diagnosed with pancreatic CC and pancreatic ductal adenocarcinoma (PDAC) between 2004 and 2016 were identified from the National Cancer Database using International Classification of Disease-O-3 morphology (8480/3 and 8140/3) and topography (C25) codes. Kaplan-Meier analysis and Cox proportional hazards models were used to analyze OS. RESULTS: Fifty-six thousand eight hundred forty-six patients were identified. A total of 2430 patients (4.3%) were diagnosed with pancreatic CC. Males constituted 52.8% of CC and 52.2% of PDAC. Colloid carcinoma presented with pathological stage I disease more often (16.7% vs 5.9%) and stage IV disease less often (42.1% vs 52.4%) than PDAC (P < 0.001). Stage I CC received chemotherapy (36.0% vs 59.4%) and neoadjuvant chemotherapy (4.4% vs 14.2%) less often compared with PDAC (P < 0.001). Statistically significant improved OS was seen among stage I, II, and IV CC compared with PDAC. CONCLUSIONS: Pancreatic CC presented as stage I disease more often compared with PDAC. Neoadjuvant chemotherapy was administered more often in stage I PDAC compared with CC. Colloid carcinoma had improved OS compared with PDAC among all stages except stage III.

Role of local therapy in the management of patients with metastatic anal squamous cell carcinoma: a National Cancer Database study.

Background: About 10-20% of patients with anal squamous cell carcinoma (SCCa) present with metastatic disease and are usually treated with systemic chemotherapy. However, primary tumor control is crucial as local failure is associated with significant morbidity. Using the largest cohort to date, we report the impact of local therapy on survival among patients with metastatic anal SCCa. Methods: Data were collected from US hospitals that contributed to the National Cancer Database (NCDB) between 2004 and 2015. Patients who did not receive palliative systemic chemotherapy were excluded from analysis. Univariate (UVA) and multivariable analyses (MVA) were performed to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to evaluate the association between tumor/patient characteristics and overall survival (OS). Results: A total of 1,160 patients were identified over the 12 years of study. Median age was 57 years. Majority were female (64.9%), non-Hispanic Whites (79.1%) and had Charlson-Deyo Score of 0 (83.6%). Most common metastatic sites were liver (25.9%), lung (11.6%) and bone (8.5%). More than 79% of the patients had received radiation to the primary site, and 10.4% underwent surgical resection for local control. Use of local therapy correlated closely with OS on MVA (HR 0.66; 0.55-0.79; P<0.001), with a 12-month and 5-year OS rates of 72.8% and 25.7% respectively, compared with 61.1% and 14.6% for patients treated with chemotherapy only. Poor prognostic factors included male gender (HR 1.44; 1.24-1.67; P<0.001), age >70 years (HR 1.28; 1.02-1.62; P=0.034), lack of health insurance (HR 1.32; 1.02-1.71; P=0.034), and cloacogenic zone location (HR 4.02; 1.43-11.30; P=0.008). There was no benefit from abdominoperineal resection (mOS =19.7 months; HR 1.05; 0.48-2.29; P=0.909), but both local resection of the primary (mOS =24.8 months, HR 0.48; 0.29-0.80; P=0.005) and palliative radiation (mOS =22.6 months; HR 0.66; 0.55-0.79; P<0.001) were associated with improved OS. Conclusions: In addition to systemic therapy, resection of the primary tumor or palliative radiation improved OS in patients with anal SCCa. Patients unlikely to benefit from local control were those >70 years of age, male, lack of health insurance and cloacogenic carcinoma.

Survival Outcomes of Acinar Cell Pancreatic Cancer: A National Cancer Database Analysis.

OBJECTIVES: Acinar cell pancreatic carcinomas (ACPCs) are rare neoplasms accounting for 1% to 2% of pancreatic tumors in adults. The objective of this study is to evaluate the benefit of chemotherapy in the adjuvant setting in resected ACPC and in the palliative setting for metastatic ACPC. METHODS: Data were obtained from all US hospitals that contributed to the National Cancer Database between 2004 and 2014. Cases were identified using the histology code 8550. RESULTS: A total of 593 patients with ACPC were identified. The mean age was 64.4 years (range, 18-90 years), with a male preponderance (72.8%, n = 432). Localized stage disease comprised 52.3% (n = 310) of patients. Among localized ACPC patients, 88.0% (n = 191) underwent surgery and 50.6% (n = 91) received adjuvant chemotherapy. The 5-year overall survival in those who received adjuvant treatment was slightly higher than those who did not receive adjuvant treatment (46.7% vs 44.8%, P = 0.3271). Among advanced-stage ACPC patients, 67.6% received chemotherapy, which translated into improved 5-year overall survival compared with no chemotherapy (8.1% vs 0%, P < 0.0001). CONCLUSIONS: Chemotherapy in the palliative setting for advanced-stage ACPC patients was associated with improved survival. Adjuvant therapy did not translate into significant survival benefit.

Impact of Tumor Side on Clinical Outcomes in Stage II and III Colon Cancer With Known Microsatellite Instability Status.

BACKGROUND: Tumor sidedness as a prognostic factor in advanced stage colon cancer (CC) is well established. The impact of tumor sidedness on the clinical outcomes of stage II and III CC has not been well studied. METHODS: The National Cancer Database (NCDB) was utilized to identify patients with pathological stage II and III primary adenocarcinoma of the colon from 2010 to 2015 using ICD-O-3 morphology and topography codes: 8140-47, 8210-11, 8220-21, 8260-63, 8480-81, 8490 and C18.0, 18.2,18.3, 18.5,18.6, 18.7. Univariate (UVA) and multivariable (MVA) survival analyses and Kaplan-Meier Curves with Log-rank test were utilized to compare overall survival (OS) based on tumor location and treatment received. RESULTS: A total of 35,071 patients with stage II (n = 17,629) and III (n = 17,442) CC were identified. 51.3% female; 81.5% Caucasian; median age 66 (range, 18-90). Majority of stage II and III tumors were right sided, 61.2% (n = 10,794) and 56.0% (n = 9,763). Microsatellite instability high (MSI-H) was more common in stage II compared to III, 23.3% (n = 4,115) vs 18.2% (n = 3,171) (p < 0.0001). In stage II MSI-H CC right was more common than left, 78.3% (n = 3223) vs 21.7% (n = 892). There was no significant difference in survival between stage II MSI-H left vs right (5-year OS 76.2 vs 74.7%, p = 0.1578). Stage II MSS CC right was more common than left, 56.0% (n = 7571) vs 44.0% (n = 5943), and survival was better in the left vs right (5-year OS 73.2 vs 70.8%, p = 0.0029). Stage III MSI-H CC was more common in the right than in the left, 75.6% (n = 2,397) vs 24.4% (n = 774) and survival was better in the left (5-year OS 62.5 vs 56.5%, p = 0.0026). Stage III MSS CC was more common in the right than in the left, 51.6% (n = 7,366) vs 48.4% (n = 6,905), and survival was better in the left vs right (5-year OS 67.0 vs 54.4%, p < 0.001). CONCLUSION: Survival was better in left sided tumors compared to right in stage II MSS, stage III MSS, and stage III MSI-H CC.

Predictive and Prognostic Effects of Primary Tumor Size on Colorectal Cancer Survival.

BACKGROUND: Pathologic staging is crucial in colorectal cancer (CRC). Unlike the majority of solid tumors, the current staging model does not use tumor size as a criterion. We evaluated the predictive and prognostic impact of primary tumor size on all stages of CRC. METHODS: Using the National Cancer Database (NCDB), we conducted an analysis of CRC patients diagnosed between 2010 and 2015 who underwent resection of their primary cancer. Univariate and multivariate analyses were used to identify predictive and prognostic factors, Kaplan-Meier analysis and Cox proportional hazards models for association between tumor size and survival. RESULTS: About 61,000 patients met the inclusion criteria. Median age was 63 years and majority of the tumors were colon primary (82.7%). AJCC stage distribution was: I - 20.1%; II - 32.1%; III - 34.7% and IV - 13.1%. The prognostic impact of tumor size was strongly associated with survival in stage III disease. Compared to patients with tumors <2cm; those with 2-5cm (HR 1.33; 1.19-1.49; p<0.001), 5-10cm (HR 1.51 (1.34-1.70; p<0.001) and >10cm (HR 1.95 (1.65-2.31; p<0.001) had worse survival independent of other variables. Stage II treated without adjuvant chemotherapy had comparable survival outcomes (HR 1.09; 0.97-1.523; p=0.148) with stage III patients who did, while Stage II patients who received adjuvant chemotherapy did much better than both groups (HR 0.76; 0.67-0.86; p<0.001). Stage III patients who did not receive adjuvant chemotherapy had the worst outcomes among the non-metastatic disease subgroups (HR 2.66; 2.48-2.86; p<0.001). Larger tumors were associated with advanced stage, MSI high, non-rectal primary and positive resection margins. CONCLUSIONS: Further studies are needed to clarify the role of tumor size in prognostic staging models, and how to incorporate it into therapy decisions.

Role of Resection of the Primary in Metastatic Well-Differentiated Neuroendocrine Tumors.

OBJECTIVE: Resection of the primary (RP) in metastatic neuroendocrine tumor (NET) is controversial. The aim was to evaluate survival outcomes for RP in metastatic NET patients. METHODS: Data were obtained from US hospitals at the National Cancer Database between 2004 and 2014. χ2, analysis of variance tests, univariate, and multivariate cox proportional hazards models were evaluated. Kaplan-Meier curves and log-rank tests conducted to compare the survival difference of patient characteristics. RESULTS: A total of 2361 patients were identified. The mean age was 62.1 years (standard deviation, 13 years), male-to-female ratio 1:1; 33% were small intestine, 26.3% pancreas, and 24.4% lung; 69.6% were well-differentiated; and 42.5% underwent RP. The 5-year overall survival (OS) was significantly improved for patients who underwent RP in small intestine (5-year OS, 63.9% vs 44.2%), lung (5-year OS, 65.4% vs 20.2%), and pancreas tumors (5-year OS, 75.6% vs 30.6%). On multivariate analysis, RP (hazard ratio, 0.46; 95% confidence interval, 0.29-0.73; P < 0.001), female, year of diagnosis 2010-2014, margin, Charlson-Deyo score less than 2, and age less than 51 years, were associated with better OS. CONCLUSIONS: Resection of the primary in metastatic well-differentiated NET is associated with improved OS compared with no RP.

Impact of Sarcopenia, BMI, and Inflammatory Biomarkers on Survival in Advanced Hepatocellular Carcinoma Treated With Anti-PD-1 Antibody.

BACKGROUND: Sarcopenia and inflammation are independently associated with worse survival in cancer patients. This study aims to determine the impact of sarcopenia, body mass index (BMI), and inflammatory biomarkers on survival in advanced hepatocellular carcinoma (HCC) patients treated with anti-PD-1 antibody-based immunotherapy. METHODS: A retrospective review of advanced HCC patients treated with immunotherapy at Winship Cancer Institute between 2015 and 2019 was performed. Baseline computed tomography and magnetic resonance images were collected at mid-L3 level, assessed for skeletal muscle density using SliceOmatic (TomoVision, version 5.0) and converted to skeletal muscle index (SMI) by dividing it by height (m2). Sex-specific sarcopenia was defined by the median value of SMI. The optimal cut for continuous inflammation biomarker was determined by bias-adjusted log-rank test. Overall survival (OS) was set as primary outcome and Cox proportional hazard model was used for association with survival. RESULTS: A total of 57 patients were included; 77.2% male, 52.6% Caucasian, 58.5% Eastern Cooperative Oncology Group performance status 0-1, 80.7% Child Pugh A. Treatment was second line and beyond in 71.9% of patients. The median follow-up time was 6 months. Sarcopenia cut-off for males and females was SMI of 43 and 39, respectively. 49.1% of patients had sarcopenia. Median OS was 5 versus 14.3 months in sarcopenic versus nonsarcopenic patients (Log-rank P=0.054). Median OS was 5 and 17.5 months in patients with BMI <25 and BMI ≥25, respectively (Log-rank P=0.034). Median OS was 3.6 and 14.3 months for patients with neutrophil-to-lymphocyte ratio (NLR) ≥5.15 versus NLR <5.15 (Log-rank P<0.001). In multivariable Cox regression model, higher baseline NLR was associated with worse OS (hazard ratio [HR]: 4.17, 95% confidence interval [CI]: 1.52-11.39, P=0.005). Sex-specific sarcopenia showed a trend of worse OS (HR: 1.71, 95% CI: 0.73-4.00, P=0.215) but was not statistically significant. BMI<25 was associated with worse OS (HR: 2.28, 95% CI: 0.92-5.65, P=0.076). In the association with progression free survival, neither baseline BMI nor sex-specific sarcopenia showed statistical significance. CONCLUSION: After controlling for baseline Child Pugh score and NLR, sex-specific sarcopenia does not predict OS. Baseline BMI and NLR together may predict OS in advanced HCC patients treated with anti-PD-1 antibody.

Is adjuvant chemotherapy beneficial for stage II-III goblet cell carcinoid/goblet cell adenocarcinoma of the appendix?

BACKGROUND: Goblet cell carcinoma (GCC), formerly known as goblet cell carcinoid, of the appendix constitutes less than 14% of all primary appendiceal neoplasms. Surgical resection is the main treatment and the role of adjuvant chemotherapy (AC) is not established. This study aims to evaluate the impact of AC in stage II-III appendiceal GCC. METHODS: Patients with pathological stage II and III GCC who underwent surgical resection between 2006 and 2015 were identified from the National Cancer Database (NCDB) using ICD-O-3 morphology and topography codes: 8243/3 (goblet cell carcinoid) and C18.1. Patients treated with neoadjuvant systemic and/or radiation therapy and adjuvant radiation were excluded. Univariate and multivariable analyses were conducted, and Kaplan-Meier Curves were used to compare overall survival (OS) based on treatment received with Log-rank test. RESULTS: A total of 619 patients were identified. 54.4% males and 89.0% Caucasian; median age 56 (range, 23-90) years. Distribution across pathological stages II-III was 82.7% (N = 512) and 17.3% (N = 107) respectively. AC was administered in 9.4% (N = 48) of stage II and 47.7% (N = 51) of stage III patients. For stage II patients, AC was not associated with better OS in univariate (HR 0.32; 95% CI 0.04-2.34; p = 0.261) or multivariable analyses (HR 0.29; 95% CI 0.04-2.12; p = 0.221). By contrast, in stage III patients, AC was associated with better OS in univariate (HR 0.35; 95% CI 0.17-0.71; p = 0.004) and multivariable analyses (HR 0.25; 95% CI 0.07-0.88; p = 0.031). In the entire cohort 5-year OS for patients that received AC was 85.5% (74.0%, 92.1%) versus 82.7% (77.5%, 86.8%) (p = 0.801) with no AC. For stage II patients, 5-year OS was 96.9% with AC vs. 89.1% with no AC (p = 0.236). For stage III patients, 5-year OS was 77.1% with AC vs. 42.8% with no AC (p = 0.003). CONCLUSION: AC was associated with improved OS in patients with pathological stage III GCC of the appendix, but not with pathological stage II.

Impact of high-risk features for stage II adenocarcinoma of the appendix.

BACKGROUND: Clinico-pathological high-risk features are frequently utilized in adjuvant chemotherapy (AC) decisions in stage II colorectal cancer and their utility in stage II appendiceal adenocarcinoma (AA) is not established. The aim of this study is to determine the impact of high-risk features in clinical outcomes and whether high risk features are predictive of AC benefit in stage II AA. METHODS: Patients with pathological stage II AA between 2010 and 2015 were identified from the National Cancer Database (NCDB) using ICD-O-3 morphology and topography codes: 8140, 8480 and C18.1. High risk stage II AA was defined as having at least one of the following clinicopathological features: T4 tumor, <12 lymph nodes examined, poorly differentiated histology, positive margins, or lymphovascular invasion. Patients with none of these features were defined as low-risk. RESULTS: A total of 1040 patients with pathological stage II AA were identified. 51.0% males, 84.5% Caucasian; median age 61 (range, 19-90). 46.4% were determined to have high-risk stage II AA. High-risk status was associated with worse OS compared to low-risk in univariate (HR 1.55; 95% CI 1.18-2.02; p = 0.001) and multivariable analyses (HR 1.36; 95% CI 1.03-1.79; p = 0.028). High-risk stage II AA patients had significantly worse 5-year OS compared to low-risk patients (67.1% vs. 74.5%, p = 0.0013). AC was administered in 34.4% (n = 166) of high-risk patients and in 36.5% (n = 203) of low-risk patients. Among high-risk patients, AC was not associated with better OS in univariate (HR 0.86; 95% CI 0.59-1.26; p = 0.448) and multivariable analyses (HR 1.35; 95% CI 0.90-2.04; p = 0.151) compared to no AC. Similarly, among low-risk patients, AC was not associated with better OS in univariate (HR 0.92; 95% CI 0.60-1.39; p = 0.679) and multivariable analyses (HR 1.27; 95% CI 0.81-2.02; p = 0.299) compared to no AC. For high-risk patients, 5-year OS was 68.3% in patients that received AC vs. 66.5% in patients that did not (p = 0.722). For low-risk patients, 5-year OS was 74.0% in patients that received AC vs. 76.3% in patients that did not (p = 0.813). CONCLUSION: High-risk stage II AA patients had significantly worse 5-year OS compared to low-risk patients. AC did not improve survival regardless of high-risk features in stage II AA in this retrospective study. A prospective randomized clinical trial would be required to determine the impact of high-risk features on AC in stage II AA.

Clinical Nutrition and Human Rights. An International Position Paper.

The International Working Group for Patients' Right to Nutritional Care presents its position paper regarding nutritional care as a human right intrinsically linked to the right to food and the right to health. All people should have access to food and evidence-based medical nutrition therapy including artificial nutrition and hydration. In this regard, the hospitalized malnourished ill should mandatorily have access to screening, diagnosis, nutritional assessment, with optimal and timely nutritional therapy in order to overcome malnutrition associated morbidity and mortality, while reducing the rates of disease-related malnutrition. This right does not imply there is an obligation to feed all patients at any stage of life and at any cost. On the contrary, this right implies, from an ethical point of view, that the best decision for the patient must be taken and this may include, under certain circumstances, the decision not to feed. Application of the human rights-based approach to the field of clinical nutrition will contribute to the construction of a moral, political, and legal focus to the concept of nutritional care. Moreover, it will be the cornerstone to the rationale of political and legal instruments in the field of clinical nutrition.

Clinical nutrition and human rights. An international position paper.

The International Working Group for Patients' Right to Nutritional Care presents its position paper regarding nutritional care as a human right intrinsically linked to the right to food and the right to health. All people should have access to food and evidence-based medical nutrition therapy including artificial nutrition and hydration. In this regard, the hospitalized malnourished ill should mandatorily have access to screening, diagnosis, nutritional assessment, with optimal and timely nutritional therapy in order to overcome malnutrition associated morbidity and mortality, while reducing the rates of disease-related malnutrition. This right does not imply there is an obligation to feed all patients at any stage of life and at any cost. On the contrary, this right implies, from an ethical point of view, that the best decision for the patient must be taken and this may include, under certain circumstances, the decision not to feed. Application of the human rights-based approach to the field of clinical nutrition will contribute to the construction of a moral, political and legal focus to the concept of nutritional care. Moreover, it will be the cornerstone to the rationale of political and legal instruments in the field of clinical nutrition.

Acute myocardial injury after administration of intravenous epinephrine for allergic reaction.

Myocardial injury or infarction in the setting of anaphylaxis can be due to anaphylaxis itself, known as Kounis syndrome, or as a result of treatment with epinephrine. Myocardial ischemia caused by therapeutic doses of epinephrine in the setting of anaphylaxis is a rare event attributed to coronary artery vasospasm. A 41-year-old female with past medical history of recurrent costochondritis, chronic thrombocytopenia, and nonspecific palindromic rheumatism presented to the emergency department with perioral numbness, flushing and throat tightness after a meal containing fish and almonds. Intramuscular epinephrine was ordered but inadvertently administered intravenously, after which she developed sharp, substernal chest pain and palpitations. Electrocardiogram showed normal sinus rhythm with QT interval prolongation. Troponin peaked at 1.41 ng/mL. She was given 324 mg of aspirin in the emergency department. Transthoracic echocardiogram showed normal ejection fraction with lateral wall motion abnormality. We present a case of a patient with no significant risk factors for coronary artery disease who developed myocardial injury following inadvertent IV administration of a therapeutic dose of epinephrine for an anaphylactic-like reaction. The development of myocardial injury after epinephrine is rare, with only six reported cases in literature and just one after intravenous administration. This is the first described case of known myocardial injury without ST-T wave changes on electrocardiogram . The proposed mechanism is an alpha-1 receptor-mediated coronary vascular spasm resulting in myocardial ischemia. The aim of this case is to raise awareness of the potential for acute myocardial injury after inadvertent intravenous administration of epinephrine for anaphylaxis, even in patients with no known risk factors for coronary artery disease, as well as to demonstrate that this clinical scenario can present regardless of troponin elevation and without ST-T wave ECG changes.

Nonbacterial Thrombotic Endocarditis and Widespread Skin Necrosis in Newly Diagnosed Lung Adenocarcinoma.

Nonbacterial thrombotic endocarditis (NBTE) is a rare entity most commonly diagnosed postmortem with rates in autopsy series ranging from 0.9 to 1.6%. A 63-year-old female with past medical history of hypertension and mitral valve prolapse presented to the hospital with shortness of breath, headache, and necrotic skin lesions on her hands and feet. Computed tomography (CT) scan of her chest demonstrated a pulmonary embolus in the right lower lung segmental artery and right upper lobe lobar to segmental pulmonary artery, a mass-like consolidation in the left upper lung field impeding the hilum. CT scan of the abdomen demonstrated metastatic disease in liver and bone and bilateral femoral deep vein thrombosis. Transesophageal echocardiography revealed severe mitral regurgitation with two small mobile plaques on the mitral valve and two immobile plaques on the descending aorta. Magnetic resonance imaging of the brain was consistent with subacute infarcts and metastatic disease. Bronchoscopy was performed and pathology revealed primary adenocarcinoma of the lung. She was treated with anticoagulation and systemic chemotherapy. The patient and family elected to proceed with hospice due to her clinical decline, poor performance status, and poor prognosis after a prolonged hospital stay. Underlying malignancy is detected in approximately 40-85% of patients with NBTE. Lung cancer is the most frequently associated malignancy followed by pancreatic, stomach, breast, and ovarian cancer. Widespread necrotic skin lesions as presenting symptoms of primary lung adenocarcinoma are rare. In the present case, the diagnosis of necrotic skin lesions and NBTE preceded that of the neoplastic disease. Necrotic skin lesions and NBTE can be the first manifestations of an occult malignancy causing extensive multi-organ infarcts. NBTE can present with such extensive skin lesions as a first presenting sign of malignancy. To the best of our knowledge, this is the first case to present with such extensive skin lesions as the first presenting symptom of lung adenocarcinoma.