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

Tracheo-bronchial lesions with air leak are rare but a catastrophic complications of esophageal resections. We analyzed the management and outcome of 31 patients who developed a non-malignant lesion of the trachea or main stem bronchus after esophagectomy for esophageal cancer. All patients initially required endotracheal intubation to control respiratory distress. A modified respiratory therapy with a reduced tidal volume and high respiratory rate markedly decreased the air leakage from 2.8 to 1.1/min (P < 0.001). Early extubation was possible in 23 patients with a complete healing or decrease of the fistula size. Jet ventilation, endoluminal stenting of the fistula, bronchoscopic fibrin sealing of the fistula, and surgical closure of the fistula with a muscular pedicle flap were attempted with variable success in patients with otherwise not manageable air leaks. Ten of the 31 patients (33%) died during the postoperative course, in eight out of 10 patients, postoperative mortality resulted from an unhealed lesions at the bifurcation or in the left main stem bronchus. These data show that reduction of airway pressure and spontaneous breathing are the key to closure of the airway leak. The entire armamentarium of respiratory, bronchoscopic, and surgical techniques must be available for a successful management of these patients.

Respiratory management and outcome of non-malignant tracheo-bronchial fistula following esophagectomy.

Expression of prostaglandin E synthase (PGES) - an enzyme of the prostaglandin biosynthetic pathway with suspected impact on carcinogenesis--was studied in Barrett's cancer to determine its pathogenetic role and prognostic impact in this entity. Expression analysis of PGES was performed on mRNA level (quantitative reverse transcription polymerase chain rection [RT-PCR]) in a large surgical series of 123 primary resected adenocarcinomas of the distal esophagus (Barrett's cancer). Gene expression results were correlated with clinical parameters, overall survival and expression levels of previously analyzed target genes of the cyclooxygenase (COX) pathway (COX-1, COX-2) and mediators of angiogenesis (vascular endothelial growth factor [VEGF]-A) and lymphangiogenesis [VEGF-C]. Expression of PGES was demonstrated in all 123 tumors (100%) on mRNA level (quantitative RT-PCR). Relative mRNA expression levels were highly variable between different cases. Gene expression showed a strong positive correlation with both COX isoforms (COX-1: r = 0.502, P < 0.001; COX-2: r = 0.679, P < 0.001), with the angiogenetic VEGF-A (r = 0.583, P < 0.001) and with the lymphangiogentic VEGF-C (r = 0.465, P < 0.001). PGES mRNA expression showed no significant correlation with clinicopathologic parameters (i.e. pTNM categories, UICC stage, survival). Variable overexpression of PGES seems to be potentially implicated in Barrett's carcinogenesis. Gene expression of PGES is strongly correlated with other mediators of the prostaglandin biosynthetic pathway, that is both COX isoforms (COX-1 and COX-2). However, no impact on patients' outcome in relation to PGES expression was found.

Expression of prostaglandin E synthase in Barrett's cancer.

Whole body hyperthermia was produced in 14 patients with conventionally incurable malignant disease. The technique consisted of arteriovenous shunting involving extracorporeal circulation with heat exchange during general anaesthesia. A temperature of 41.8 degrees C was maintained for periods of 6 hours. After achieving hyperthermic temperatures treatment was enlarged by administration of 5-fluorouracil (1000 mg) in patients with colorectal carcinoma and by dacarazine (200 mg/m2) in patients with malignant melanoma. In 5 out 6 patients with stage IV colorectal carcinoma stabilisation of the disease was seen for an average of 10 months. In contrast, progression of the disease was seen in patients with malignant melanoma and mean survival was only 5 months. These preliminary results in a small number of patients indicate that 1. induction and maintenance of whole body hyperthermia is clinically possible, 2. technical requirements are considerable, however feasible, 3. different tumours react differently to treatment.

[Extracorporeally induced whole-body hyperthermia in conventionally incurable malignant tumor patients].

A case of an acute abdomen caused by a massive intrahepatic hemorrhage in a 77-year old man is presented. The hemorrhage was the first manifestation of an underlying polyarteritis nodosa which had not been diagnosed prior to the event. The diagnosis was suspected after a preoperatively performed angiography, surgical treatment was required to control the bleeding. This case demonstrates the differential diagnosis of acute intrahepatic hemorrhage which includes rare causes of vasculitis.

Massive intrahepatic hemorrhage as first manifestation of polyarteritis nodosa.

Raise Your Head Reflux often strikes when you are laying down flat, because stomach fluid can flow back more easily. Try raising the head of your bed 4-6” by sliding blocks or books under the legs at the head of your bed, or place a wedge under the mattress. Tilt the whole bed or mattress, rather than trying to sleep on several pillows, which increases pressure on your stomach and can actually make GERD worse.

J. R. Siewert

Papers

Respiratory management and outcome of non-malignant tracheo-bronchial fistula following esophagectomy.

Expression of prostaglandin E synthase in Barrett's cancer.

[Extracorporeally induced whole-body hyperthermia in conventionally incurable malignant tumor patients].

Massive intrahepatic hemorrhage as first manifestation of polyarteritis nodosa.

[Gastro-esophageal reflux].