Background A regimen of epirubicin, cisplatin, and infused fluorouracil (ECF) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma. We assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer. Methods We randomly assigned patients with resectable adenocarcinoma of the stomach, esophagogastric junction, or lower esophagus to either perioperative chemotherapy and surgery (250 patients) or surgery alone (253 patients). Chemotherapy consisted of three preoperative and three postoperative cycles of intravenous epirubicin (50 mg per square meter of body-surface area) and cisplatin (60 mg per square meter) on day 1, and a continuous intravenous infusion of fluorouracil (200 mg per square meter per day) for 21 days. The primary end point was overall survival. Results ECF-related adverse effects were similar to those previously reported among patients with advanced gastric cancer. Rates of postoperative complications were similar in the perioperative-chemotherapy group and the surgery group (46 percent and 45 percent, respectively), as were the numbers of deaths within 30 days after surgery. The resected tumors were significantly smaller and less advanced in the perioperative-chemotherapy group. With a median follow-up of four years, 149 patients in the perioperative-chemotherapy group and 170 in the surgery group had died. As compared with the surgery group, the perioperative-chemotherapy group had a higher likelihood of overall survival (hazard ratio for death, 0.75; 95 percent confidence interval, 0.60 to 0.93; P = 0.009; five-year survival rate, 36 percent vs. 23 percent) and of progression-free survival (hazard ratio for progression, 0.66; 95 percent confidence interval, 0.53 to 0.81; P<0.001). Conclusions In patients with operable gastric or lower esophageal adenocarcinomas, a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival. (Current Controlled Trials number, ISRCTN93793971.)

/pdf/perioperative-chemotherapy-versus-surgery-alone-for-5bm4upx1bz.pdf

Perioperative Chemotherapy versus Surgery Alone for Resectable Gastroesophageal Cancer

https://www.chpso.org/sites/main/files/file-attachments/chest-2008-geerts-381s-453s.pdf

Prevention of Venous Thromboembolism* American College of Chest Physicians Evidence- Based Clinical Practice Guidelines (8th Edition)

Sepsis is the leading cause of death in critically ill patients in the United States. Yet the individual host response to septicemia is variable, depending on the patient's immune response, age, nutritional status, and coexisting conditions, as well as on the virulence of the organism and the size of the inoculum. This review examines evolving concepts of sepsis and discusses new and potential therapies. Recent clinical advances include therapy with activated protein C, stringent control of blood glucose, and early goal-directed therapy to treat cellular oxygen deficit. Future therapies may be focused on modulating the immune response in the light of the characteristics of the specific pathogen, the genetic profile of the patient, and the duration of the disease.

https://www.nejm.org/doi/pdf/10.1056/NEJMra021333

The pathophysiology and treatment of sepsis.

The purpose of this article is to review the status and limitations of anatomic tumor response metrics including the World Health Organization (WHO) criteria, the Response Evaluation Criteria in Solid Tumors (RECIST), and RECIST 1.1. This article also reviews qualitative and quantitative approaches to metabolic tumor response assessment with 18 F-FDG PET and proposes a draft framework for PET Response Criteria in Solid Tumors (PERCIST), version 1.0. Methods: PubMed searches, including searches for the terms RECIST, positron, WHO, FDG, cancer (including specific types), treatment response, region of interest, and derivative references, were performed. Abstracts and articles judged most relevant to the goals of this report were reviewed with emphasis on limitations and strengths of the anatomic and PET approaches to treatment response assessment. On the basis of these data and the authors’ experience, draft criteria were formulated for PET tumor response to treatment. Results: Approximately 3,000 potentially relevant references were screened. Anatomic imaging alone using standard WHO, RECIST, and RECIST 1.1 criteria is widely applied but still has

https://jnm.snmjournals.org/content/jnumed/50/Suppl_1/122S.full.pdf

From RECIST to PERCIST: Evolving Considerations for PET Response Criteria in Solid Tumors

Prevention of Venous Thromboembolism : The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy

Classification of adenocarcinoma of the oesophagogastric junction

PURPOSE: Preoperative chemotherapy in patients with gastroesophageal cancer is hampered by the lack of reliable predictors of tumor response. This study evaluates whether positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) may predict response early in the course of therapy. PATIENTS AND METHODS: Forty consecutive patients with locally advanced adenocarcinomas of the esophagogastric junction were studied by FDG-PET at baseline and 14 days after initiation of cisplatin-based polychemotherapy. Clinical response (reduction of tumor length and wall thickness by > 50%) was evaluated after 3 months of therapy using endoscopy and standard imaging techniques. Patients with potentially resectable tumors underwent surgery, and tumor regression was assessed histopathologically. RESULTS: The reduction of tumor FDG uptake (mean ± 1 SD) after 14 days of therapy was significantly different between responding (−54% ± 17%) and nonresponding tumors (−15% ± 21%). Optimal differentiation was achieve...

Prediction of Response to Preoperative Chemotherapy in Adenocarcinomas of the Esophagogastric Junction by Metabolic Imaging

Objective
To analyze the changing pattern in tumor type and postoperative deaths at a national referral center for esophageal cancer in the Western world and to assess prognostic factors for long-term survival after resection.

Histologic tumor type is an independent prognostic parameter in esophageal cancer: lessons from more than 1,000 consecutive resections at a single center in the Western world.

Purpose A previous study suggested that measurement of therapy-induced changes in tumor glucose metabolism by positron emission tomography (PET) with the glucose analog [18F]fluorodeoxyglucose (FDG) allows to select patients most likely to benefit from preoperative chemotherapy in adenocarcinomas of the esophagogastric junction (AEG). The aim of this study was to prospectively validate these findings by using an a priori definition of metabolic response. Patients and Methods Sixty-five patients with locally advanced AEGs were included. Tumor glucose utilization was quantitatively assessed by FDG-PET before chemotherapy and 14 days after initiation of therapy. Patients were classified as metabolic responders when the metabolic activity of the primary tumor had decreased by more than 35% at the time of the second PET. Results Metabolic responders showed a high histopathologic response rate (44%) with a 3-year survival rate of 70%. In contrast, prognosis was poor for metabolic nonresponders with a histopatho...

Metabolic imaging predicts response, survival, and recurrence in adenocarcinomas of the esophagogastric junction.

In a prospective multicentre study of 2394 patients with gastric carcinoma the prognostic relevance of systematic lymph node dissection was evaluated Of 1654 patients undergoing resection, 558 had a standard lymph node dissection, defined as fewer than 26 nodes in the specimen, and 1096 underwent radical lymphadenectomy, ie 26 or more nodes in the specimen Radical dissection signficantly improved the survival rate in patients with Union Internacional Contra la Cancrum (UICC) stages II and IIIA tumours Multivariate analysis identified radical dissection as an independent prognostic factor in the subgroups of patients with UICC tumour stages II and IIIA Radical dissection conferred no survival advantage in patients with pN2 tumours There was no significant difference in morbidity and mortality rates between radical and standard lymph node dissection Radical lymphadenectomy improves survival in patients with UICC gastric cancer stages II and IIIA, and should be the recommended treatment for such patients

https://bjssjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/bjs.1800820954

J. R. Siewert

Papers

Classification of adenocarcinoma of the oesophagogastric junction

Prediction of Response to Preoperative Chemotherapy in Adenocarcinomas of the Esophagogastric Junction by Metabolic Imaging

Histologic tumor type is an independent prognostic parameter in esophageal cancer: lessons from more than 1,000 consecutive resections at a single center in the Western world.

Metabolic imaging predicts response, survival, and recurrence in adenocarcinomas of the esophagogastric junction.

Prognostic relevance of systematic lymph node dissection in gastric carcinoma