Cooleyloomis0645

Background The only possibility for cure in patients with colon adenocarcinoma (CAC) with isolated liver metastases (ILM) is resection of both primary and metastatic tumors. Little is known about the implication of the sequence in which a colectomy and hepatectomy are performed on outcomes. This study analyzes whether resection sequence impacts clinical outcomes. Methods The National Cancer Database was queried for CAC cases with hepatic metastases from 2010-2015 with exclusion of extrahepatic metastases. We compared patients treated with a liver-first approach (LFA) to those treated with a colectomy-first or simultaneous approach using Kaplan Meier and multivariable Cox proportional hazards analysis. Results In 21,788 CAC patients identified, the LFA was uncommon (2%), but was associated with higher rates of completion resection of remaining tumor (41% vs. 22%, P less then 0.001). Patients selected for LFA were younger, less comorbid, and more commonly received upfront chemotherapy (P less then 0.05). The LFA was associated with increased median survival [34 months, 95% CI (30.5-39.6 months) vs. 24 months, 95% CI (23.7-24.6 months), logrank P less then 0.001] and decreased risk of death [HR 0.783; 95% CI (0.67-0.89), P=0.001]. Conclusions The LFA to CAC with synchronous ILM is uncommon but is associated with greater likelihood of receiving chemotherapy prior to surgery and increased survival in selected candidates. 2020 Journal of Gastrointestinal Oncology. All rights reserved.Background The incidence of esophageal cancer (EC) is increasing in the USA. Neoadjuvant therapy for locally advanced cancers followed by surgical resection is the standard of care. The most common post-esophagectomy cardiac complication is atrial fibrillation (AF). New-onset postoperative AF can require a prolonged hospital stay and may confer an overall poorer prognosis. In this study, we seek to identify clinical factors associated with postoperative AF. Methods Query of an IRB approved database of 1,039 esophagectomies at our institution revealed 677 patients with EC from 1999 to 2017 who underwent esophagectomy after neoadjuvant treatment. Age, treatment location (primary vs. other), gender, neoadjuvant radiation type [2D vs. 3D vs. intensity modulated radiation therapy (IMRT)], radiation dose, surgery type (transthoracic vs. transhiatal vs. three field), smoking history, coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD), operative time, blood transfusions, fluid management, anditored more closely in the postoperative setting and potentially referred earlier preoperatively for cardio-oncology assessment. Future study is required to determine if modification of current radiation techniques and cardiac dose constraints in this patient population may be warranted. 2020 Journal of Gastrointestinal Oncology. All rights reserved.Background Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with limited therapeutic options. We evaluated the safety and efficacy of the aminopeptidase inhibitor tosedostat with capecitabine in advanced PDAC. Methods We conducted a phase Ib/II trial of tosedostat with capecitabine as second-line therapy for advanced PDAC. Planned enrollment was 36 patients. Eligible patients were treated with capecitabine 1,000 mg/m2 oral twice-daily days 1-14 and oral tosedostat in a dose de-escalation design on days 1-21 of each 21-day cycle. Primary endpoints were the recommended phase 2 dose (RP2D) and progression-free survival (PFS). Results Sixteen patients were enrolled. Tosedostat 120 mg oral twice daily with capecitabine 1,000 mg/m2 oral twice daily was the RP2D. There was one dose-limiting toxicity (DLT) (grade 3 acute coronary syndrome) during phase Ib. The most common treatment-related adverse events were gastrointestinal (nausea, diarrhea), cardiac [QTc prolongation, decreased ejection fraction (EF)], and fatigue. The median PFS was 7.1 months, and the median treatment failure free survival was 3 months. Eight patients experienced stable disease for greater than 3 months. The study was closed early due to lack of drug availability. Conclusions Tosedostat with capecitabine displayed tolerable toxicity, and prolonged disease control in a subset of patients. These data encourage further exploration of aminopeptidase inhibitors in pancreatic cancer. 2020 Journal of Gastrointestinal Oncology. All rights reserved.Background Von Hoff et al. demonstrated survival improvement with gemcitabine (GEM) + nab-paclitaxel (NabP) for metastatic pancreatic ductal adenocarcinoma (PDAC) compared to GEM alone. GEM + NabP resulted in a median overall survival (OS) and progression-free survival (PFS) of 8.5 and 5.5 months, respectively. Patients with baseline hyperbilirubinemia were excluded. Primary objective was OS. Secondary objectives included time on treatment (TOT), disease control rate, dosing practices, delays/admissions, and adverse effects. Methods Patients with borderline resectable, locally advanced, or metastatic PDAC who initiated front-line GEM-NabP during July 01, 2013-July 01, 2017 were reviewed. Patients with a baseline total bilirubin ≥2 mg/dL were included. Results Twelve patients total were included. Median age was 71 years old. Median baseline total bilirubin was 2.4 mg/dL (range, 2.1-5.2 mg/dL). 58% had metastatic disease. Median doses were NabP 100 mg/m2 + GEM 600 mg/m2 IV with a fixed-dose rate infusion (10 mg/m2/min). GEM-NabP was given biweekly or 3 weeks on 1 week off. Median OS, TOT, and disease control rate were 13.9, 5.2 months, and 58%, respectively. Fifty percent of patients required a dose delay. Metastatic patients only (n=7) had median OS and TOT of 6.9 and 2.1 months, respectively. No admissions related to toxicity were found. Conclusions Our analysis revealed safety with NabP (median dose =100 mg/m2) + GEM (median dose =600 mg/m2 at fixed-dose rate) given predominately biweekly in patients with a baseline elevated total bilirubin (≥2 mg/dL). 2020 Journal of Gastrointestinal Oncology. All rights reserved.Background Genetic analysis of gastrointestinal malignancies shows a great number of mutations. read more Most mutations found in gastric tumors are also found in colorectal and esophageal tumors. The challenge remains to identify mutations that distinguish gastric from colorectal and esophageal cancers. Using open-access cancer genomics data, we sought to identify mutations that accounted for the unique phenotypic features of gastric tumors. Methods Thirteen cancer genomics datasets with demographic, clinical, and genetic variables were analyzed. Pathologic stage and histology were compared between subjects with and without a specific mutated gene using two-sample t-tests, adjusted for multiple gene testing. Sequence convergence and functional impact of genetic mutations were analyzed using permutation test and PolyPhen-2 score. Results Analysis included 1,915 subjects with valid pathologic stage and histology. Mean age was 68 years (SD =10). About 54% were female. The most common race was Caucasian (37%) while minorities were rare with high rates of missing data (44%).