Novel Prognostic Factors in Resected Small Bowel Adenocarcinoma

BackgroundSmall bowel adenocarcinoma (SBA) is a rare malignancy affecting approximately 3000 patients per year in the United States, and there is limited evidence prognosticating patients with resected SBA. We aimed to evaluate prognostic factors and the role of adjuvant therapy in patients with resected SBA.Patients and MethodsTwo hundred forty-one patients who had resected stage I-III SBA were retrospectively identified at a single tertiary referral institution. Overall survival (OS) analysis was performed by the Kaplan-Meier method, and Wilcoxon tests were used for statistical comparisons. Cox proportional hazards were performed to identify significant variables by univariate and multivariate analysis.ResultsMedian OS for the entire group was 54.5 months (95% confidence interval [CI], 37.2-81.2 months), with 5- and 10-year OS of 48% and 35%. Median follow-up was 113.7 months (95% CI, 97.9-126.6 months). For patients with stage III disease who received adjuvant therapy, the median OS was 33.8 months (95% CI, 27.8-78.8) compared to 24.7 months (95% CI, 11.5-37.8) for patients with no adjuvant therapy (P < .01). Male sex, advanced T stage, advanced N stage, increased positive lymph node ratio, lymphocyte-to-monocyte ratio < 1.56, presence of residual disease, and earlier date of diagnosis predicted worse survival on univariate analysis. Age > 60 years, lymphocyte-to-monocyte ratio < 1.56, and advanced T stage were identified as independent negative predictors of OS for all patients by multivariate analysis.ConclusionAdvanced age, advanced T stage, and lymphocyte-to-monocyte ratio < 1.56 independently predicted survival in resected SBA. Adjuvant therapy is associated with improved survival in patients with resected stage III SBA.     

食管—胃交界癌根治术后的疗效观察及预后因素分析

[目的]回顾性分析食管—胃交界癌根治术后患者的远期生存情况,并探讨其预后影响因素。[方法]收集2000年10月至2002年10月间行食管—胃交界癌根治术治疗的137例患者的临床病理资料,对所有患者治疗结果进行随访。Kaplan-Meier法行生存分析,Cox比例风险模型筛选独立的预后影响因素。[结果]本组患者平均生存时间为(38.0±2.52)个月,中位生存时间为25个月;5年总生存率和无瘤生存率分别为32.9%、32.5%。单因素分析结果显示临床分期、T分期、N分期、性别、年龄、肿瘤最长径、术后化疗、清扫淋巴结总数、上瘤距、下瘤距对治疗预后有显著影响。Cox多因素分析显示T分期、N分期、术后化疗、下瘤距、清扫淋巴结总数为独立的预后影响因素。[结论]术后辅助化疗可明显提高患者生存期。肿瘤切除范围包括7cm以上正常食管和胃组织,可避免绝大多数切缘阳性。食管—胃交界癌根治术淋巴结清扫多于9枚患者有明显生存获益。     

Clinical Outcomes of Small Bowel Adenocarcinoma

BackgroundSmall bowel adenocarcinomas (SBAs) are rare tumors. Management of SBA is extrapolated from colorectal cancer treatments. Recent evidence suggests that the biology and molecular features of SBA differ from colorectal cancer. The aim of this study was to evaluate the management and outcome of SBA patients.Patients and MethodsThe National Cancer Data Base (NCDB) was queried for patients with SBA between 2004 and 2013 using ICD-O-3 histology code 8140/3 and topography codes C17.0, C17.1, C17.2, C17.8, and C17.9. Univariate and multivariate survival analyses were conducted to analyze the association between SBA location and overall survival (OS) stratified by stage. Treatment outcomes of surgery, radiation, and systemic therapy were compared.ResultsA total of 7954 SBA patients were identified; duodenum (D) 4607 (57.9%), jejunum (J) 1241 (15.6%), ileum (I) 857 (10.8%), and unspecified 1249 (15.7%). A total of 53.6% patients were male, and 76.6% white. Median age was 66 years. D mostly presented as stage IV disease (37.6%), J as stage II (34.5%) and IV disease (33.8%), and I as stage II (32.2%) and III (30.3%) disease (P < .001). Grade distribution was similar among D, J, and I; the majority were moderately differentiated (40.8%-55.0%), followed by poorly differentiated (30.9%-35.8%) and well differentiated (6.0%-12.4%) (P < .001). D underwent surgery (50.2%) less often than J (90.8%) and I (94.5%) (P < .001). Adjuvant radiation was provided in 8.5% of D, 2.6% of J, and 2.1% of I (P < .001). Adjuvant chemotherapy was provided in 21.9% of D, 50.2% of J, and 42.0% of I (P < .001). The rate of adjuvant chemotherapy was the highest in patients with stage III SBA, and was as follows: D (43.4%), J (65.4%), and I (63.6%) (P < .001). In univariate and multivariate analyses of all patients, adjuvant chemotherapy was associated with improved OS in stage II-III SBA patients. J had the best 5-year OS rate (42.0%; 95% confidence interval, 38.8-45.1, P < .001), and D had the worst (23.0%; 95% confidence interval, 21.6-24.2, P < .001). In multivariate analysis stratified by stage, chemotherapy was associated with improved OS in patients with stage II-IV SBA.ConclusionMost SBA patients present with stage IV disease. D underwent surgery less often than J and I. Stage II and III D received adjuvant chemotherapy less often compared to stage II and III J and I. Adjuvant chemotherapy was associated with improved OS in patients with stage II-III disease. J had the best 5-year OS rate, and D had the worst.     

The Evolving Use of Prognostic Factors After Resection of Colorectal Liver Metastases

The expanding use of surgical therapy for patients with colorectal liver metastases (CRLM) and developments in chemotherapeutic regimens have led to a significant improvement in survival. However, outcomes can vary substantially and criteria for determining the prognosis of individual patients are lacking. Traditionally, clinicopathologic factors, for example primary tumor stage, number and size of liver metastases, preoperative carcinoembryonic antigen levels, presence of extrahepatic disease, and others, have been used to determine which patients are more likely to experience recurrence and poor survival. However, these factors, both separately and as part of scoring systems, have been inconsistent and conflicting in determining prognosis. Recently, molecular and biological indicators have emerged as potential prognosticators for CRLM patients undergoing hepatic resection. Tumor response to chemotherapy, both on imaging and on pathology, mutation status of such oncogenes as KRAS and BRAF, and expression patterns of proliferative markers including MACC1 and Ki-67, have all furnished promising results in prediction of patient outcomes. Moreover, circulating tumor cells and tumor DNA may not only be a useful prognostic instrument but also an excellent means of screening for early detection of recurrence.     

影响食管癌切除术后患者预后的多因素分析

目的探讨影响食管癌切除术后患者预后的因素.方法从525例食管癌患者的临床病理和随访资料中选择12项指标,先后进行单因素和逐步Cox回归分析,建立术后生存预测模型.结果淋巴结转移数目、TNM分期、肿瘤浸润深度、肿瘤长度和生长部位是影响患者预后的主要因素(P＜0.01);预后指数值小的患者预后好.结论淋巴结转移是影响食管癌切除术后患者预后的最主要因素,为提高患者预后,应加强对区域淋巴结的处理;可应用预测模型来预测不同患者的术后生存率.     

Clinicopathological Characteristics and Prognosis of Patients According to Recurrence Time After Curative Resection for Colorectal Cancer

Purpose: To investigate clinicopathological features in patients with recurrent colorectal cancer within 1 yearand more than 1 year after curative resection. Materials and Methods: We retrospectively evaluated 103 patientswith disease recurrence before versus after 1 year of resection. Thirty-two patients (31%) were diagnosed withrecurrence less than 1 year after curative resection for colorectal cancer (early recurrence) and 71 (69%) after morethan 1 year (non-early recurrence). Results: The early recurrence group displayed a significantly lower overallsurvival rate for both colon cancer (p=0, 01) and rectal cancer (p<0.001). Inadequate lymph node dissection wasa significant predictor for early relapse. There were no statistically significant differences in clinicopathologicalvariables such as age, sex, primary tumor localization, stage, depth of invasion, lymphovascular invasion andperineural invasion between the early and non-early recurrence groups. However, a K-ras mutation subgroupwas significantly associated with early recurrence (p<0.001). Conclusions: Poor survival is associated with earlyrecurrence for patients undergoing resection for non-metastatic colorectal cancer, as well as K-ras mutation.     

Evaluation of Bevacizumab in Advanced Small Bowel Adenocarcinoma

Background

Small bowel adenocarcinomas (SBAs) are rarely seen tumors. Data regarding the use of chemotherapy together with bevacizumab in patients with advanced SBA are lacking. The aim of this study was the evaluation of treatment with bevacizumab in advanced SBA.

肌层浸润性膀胱癌根治术患者的预后影响因素分析

目的 分析肌层浸润性膀胱癌根治术患者的预后影响因素.方法 选取肌层浸润性膀胱癌患者71例,统计1年生存率,收集患者年龄、性别、肿瘤直径等信息,分析预后影响因素.结果 本组71例患者,1年生存率为88.73％(63/71).肿瘤直径、肿瘤数量、有无淋巴结转移、有无术前新辅助化疗、有无术后辅助放化疗是肌层浸润性膀胱癌患者术...     

Analysis of Clinicopathological Features and Prognostic Factors of Desmoplastic Small Round Cell Tumor

Desmoplastic small round cell tumor (DSRCT) is a relatively uncommon and highly aggressive malignancy in young males. It is associated with a poor outcome, due in part to missed diagnosis. To characterize the clinical pathological features of DSRCT in Chinese patients and to find out the characteristics of treatment and prognostic factors, the authors collected and analyzed the clinical information of 48 cases. A total of 48 cases of DSRCT between March 1995 and March 2012 were retrospectively reviewed and analyzed. The clinical information, histological results and survival data of the patients were collected. Median age was 26.96?±?14.09 years with a range of 6–66 years. Thirty-three patients (68.75 %) were seen before 30 years old, and 15 patients (31.25 %) were diagnosed after 30 years old. The male-to-female ratio is 3.36 :1. Among them, 37 cases presented with tumors in the abdominal or pelvic cavity; the other 11 cases had extra-abdominal tumors. The most common symptoms were abdominal pain (19/48, 39.58 %) and palpable mass (12/48, 25.00 %). The percentage of patients received surgery, complete surgery, and chemotherapy was 79.17 %, 37.50 %, and 52.08 %, respectively. Median follow-up duration was 2.67 years. Median overall survival for all patients was 24.33 months (95 % CI: 9.74–38.92 months) and median event-free survival for all patients was 8.00 months (95 % CI: 5.13–10.89 months). Univariate analysis revealed that surgery, effective debulking surgery, chemotherapy and any two or more combined therapeutics were significant prognostic factors for longer overall survival (p?<?0.05). Cox regression analysis showed complete surgery was an independent prognostic factor. Standard therapy for DSRCT consists of combination of surgical resection and postoperative chemotherapy. Complete surgery is an independent prognostic factor and should be further investigated.     

Retrospective Analysis of Taxane-Based Therapy in Small Bowel Adenocarcinoma

Currently, treatment of small bowel adenocarcinoma (SBA) mirrors that of colorectal cancer (CRC). Recent genomic data have demonstrated SBA to be a genetically unique entity, suggesting that therapies not traditionally utilized in CRC should be explored. In order to further characterize the activity of taxanes in this rare cancer, we completed a single-center retrospective study. Twenty patients were found to have been treated with taxane-based regimens (monotherapy in 3, combination therapy in 17). Median time to progression was 3.8 months (95% confidence interval [CI] 2.9–4.6), and median overall survival was 10.7 months (95% CI: 3.1–18.3). The results of this study demonstrate clinical activity from taxane-based therapy in advanced SBA and support further clinical trial investigation.     

Safety and Efficacy of Avelumab in Small Bowel Adenocarcinoma

IntroductionSmall bowel adenocarcinomas (SBAs) are rare and frequently treated like large intestinal adenocarcinomas. However, SBAs have a very different microenvironment and could respond differently to the same therapies. Our previous data suggested that SBAs might benefit from targeting the PD-1/PD-L1 axis based on PD-L1 staining in almost 50% of SBA tissue samples tested. Thus, we designed a phase 2 study to explore safety and efficacy of avelumab in SBA.Patients and MethodsPatients with advanced or metastatic disease were enrolled; ampullary tumors were considered part of the duodenum and allowed. Prior PD-1/PD-L1 inhibition was not allowed. Avelumab (10 mg/kg) was given every 2 weeks, and imaging was performed every 8 weeks. Primary endpoint was response rate.ResultsEight patients (n = 5, small intestine; n = 3, ampullary) were enrolled, with a majority (88%) being male and a median age of 61 years. Of 7 efficacy-evaluable patients, 2 (29%) experienced partial responses; stable disease occurred in 3 additional patients (71%). Median progression-free survival was 3.35 months. Most frequent, related toxicities were anemia, fatigue, and infusion-related reaction (25% each), mostly grade ≤2; grade 3 hypokalemia and hyponatremia occurred in one patient, and another reported grade 4 diabetic ketoacidosis.ConclusionsDespite the observed benefit, accrual was slower than expected and the study was closed early due to feasibility. A general clinic observation was that patients were receiving immunotherapy off-label as the availability of these agents increased. Off-label availability and disease rarity were likely drivers of insufficient accrual.     

脑膜瘤的临床病理分型及预后因素分析

目的：探讨脑膜瘤的临床病理分型及影响预后的因素。方法：用ＷＨＯ新近的良性、不典型性和恶性脑膜瘤分类，分析１１６例脑膜瘤临床和病理表现。结果：此分类与脑膜瘤复发、生存时间等预后密切相关，实用性强。患者４、５、８、１０年生存率分别为７１．４％，５５．６％，４５．９％和３７．４％，手术复发率为２０．７％，５０．９％有后遗症，１３．５％尤重。复发与手术级别密切相关。结论：Ｃｏｘ模型单因素和多因素分析，病理分类、肿瘤发生部位是影响预后的主要因素，手术级别为间接因素。ＣＴ与病理诊断配对分析两者有很好的一致性     

Chemotherapeutic Management of Small Bowel Adenocarcinoma Associated with Crohn's Disease

Abstract

Four patients with metastatic primary small bowel adenocarcinoma associated with Crohn's disease were successfully treated with low dose combination chemotherapy consisting of 5-fluorouracil, leucovorin and irinotecan with or without gemcitabine. Benefits included prolonged survival, objective responses, response of resistant tumors, downstaging, and a successful secondary complete resection (Ro) with a durable remission.     

Prognostic Significance of p53 and ras Gene Abnormalities in Lung Adenocarcinoma Patients with Stage I Disease after Curative Resection

We investigated the prognostic significance of p53 gene abnormalities and ras gene mutations in patients with curatively resected stage I lung adenocarciiioma. Formalin-fixed and paraffin-embedded tissues were obtained from 30 patients who had undergone curative resection for stage I lung adenocarciiioma. Abnormalities of the p53 gene were detected using polymcrasc chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) analysis and immunohistochemistry and ras mutations were detected using PCR-restriction fragment length polymorphism (RFLP) analysis. Both univariate and multivariate analyses were performed to assess the relationship between the presence of abnormalities of these genes and the patients'disease-free survival. Eleven tumors (37%) had mutated p53 sequences and 11 (37%) showed p53 overexpression. A total of 15 tumors (50%) had p53 gene abnormalities and the concordance rate was 73%. Seven tumors (23%) showed mutated ras sequences. The univariate analysis revealed that the disease-free survival of patients with any p53 abnormality was shorter than that of those without abnormalities ( P= 0.02, generalized Wilcoxon test), and survival of those with p53 protein overexpression was more significantly shorter ( P= 0.003, generalized Wilcoxon test). Multivariate analysis using the Cox proportional hazards model indicated that the presence of p53 abnormalities was a significantly ( P =0.01) unfavorable prognostic factor. There was no significant correlation between the presence of ras mutation and survival. These results suggest that analysis of the p53 gene may be helpful for the selection of high-risk patients for clinical trials of adjuvant therapy for stage I lung adenocarcinoma.