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.)

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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

Prophylaktische Eingriffe am Magen setzen den Nachweis molekularer oder histopathologischer pramaligner Veranderungen mit einem hohen Magenkarzinomrisiko voraus. Der Nachweis einer E-Cadherin-Keimbahnmutation geht mit einem 70–80%igen Lebenszeitrisiko fur ein diffuses Magenkarzinom, der Nachweis einer hochgradigen intraepithelialen Neoplasie mit einem 60–70%igem Magenkarzinomrisiko einher. Andere pramaligne Veranderungen wie das HNPCC-Syndrom (Magenkarzinome mit 5% an 3. Stelle) sowie eine geringgradige intraepitheliale Neoplasie (ca. 10%iges Magenkarzinomrisiko) stellen moderate Risikofaktoren fur die Magenkarzinomentstehung dar. Sie rechtfertigen keine prophylaktisch-chirurgischen wohl aber Fruherkennungsmasnahmen und bei Nachweis einer hochgradigen intraepithelialen Neoplasie bzw. eines Fruhkarzinoms die Option einer erweiterten Radikalitat im Sinne einer totalen Gastrektomie anstelle einer subtotalen Resektion. Eine positive Magenkarzinomfamilienanamnese sowie eine fruhe Magenkarzinommanifestation stellen Risikofaktoren dar, die bei der Indikationsstellung einer prophylaktischen Gastrektomie oder erweiterten Radikalitat berucksichtigt werden sollten.

Prophylaktische Chirurgie des Magens

In the majority of patients with esophageal cancer local tumor infiltration and/or distant metastases are responsible for the poor prognosis. Therefore to improve life expectancy additional modalities - chemotherapy alone or in combination with simultaneous radiation - have been introduced perioperatively. In spite of a possible increase of resectability convincing data are lacking which could argue for an uncontrolled introduction of the neoadjuvant approach outside investigational studies.

Perioperative chemotherapy in squamous cell carcinomas of the esophagus

Die radikale Ausraumung der Lymphabflusgebiete zusammen mit der kompletten Entfernung des Primartumors (Ro-Resektion) mus beim kolorektalen Karzinom als oberste Pramisse gelten, da hierdurch die Prognose gerade auch bei fortgeschrittenen Tumoren entscheidend beeinflust wird (Abb. 1). Die Erreichung dieses Ziels erfordert haufig erweiterte Eingriffe, sog. multiviszerale Resektionen und hat somit zu einer zunehmenden Aggressivitat im Bereich des Urogenitaltraktes gefuhrt. Aufgrund der engen topographisch-anatomischen Beziehungen wird dieses Organsystem zunehmend in das Resektionsausmas mit einbezogen.

Technik und Taktik chirurgischer Eingriffe im Becken bei Rektum- und Kolonkarzinom

German Society of Visceral Surgery

Purpose: Tumor targeting is defined as the specific transport of molecules to a tumor for diagnostic or therapeutic purposes. An efficient targeting vector must satisfy several challenges: molecular specificity, fast uptake in tumor cells, low immunogenic potential and the capacity to withstand degradation or inactivation. The non toxic B-subunit of the bacterial Shiga toxin (STxB) satisfies these requirements. The cellular receptor of Shiga toxin, the glycosphingolipid Gb3 (CD77), is significantly increased on a wide range of solid tumors. Studies on mouse models for human cancer showed that radioactively labelled STxB is suitable for non-invasive tumor imaging. Experimental Design: Samples of 125 malignant or benign tissues of the colorectal tract were collected, 96 were utilized for quantification of Gb3 expression levels by thin layer chromatography. In addition, the Gb3 expression of 16 pancreatic carcinomas and 13 healthy pancreata was quantified. 53 colorectal tissues were utilized for the preparation of short-term primary cell cultures. The cell cultures were treated with fluorescently labelled recombinant STxB, and uptake was monitored by immunofluorescence microscopy. Furthermore, a presumed apoptotic effect of STxB on tumor cells was investigated by labelling of cleaved caspase-3. Results: The Gb3 receptor expression is significantly increased in the majority of pancreatic carcinomas, colorectal carcinomas and liver metastasis, but not in benign adenomas, as compared to normal tissue. Intracellular STxB uptake was observed in the majority of tumor cells of every primary culture studied. In contrast, primary cultures of benign adenomas with low expression of the Gb3 receptor showed only low levels of STxB uptake. Within 60 min of uptake, STxB co-localized with the Golgi marker Golgin p97 and could be detected in intracellular vesicular compartments even five days after the initial uptake. The STxB-treatment of cells did not induce detectable levels of apoptosis as compared to untreated cell cultures. Conclusion: The data presented here demonstrate that STxB can be used for successful and specific targeting of colorectal tumor cells. Thus, STxB has great potential for future in vivo imaging applications, and also for therapeutic tumor targeting.

J. R. Siewert

Papers

Prophylaktische Chirurgie des Magens

Perioperative chemotherapy in squamous cell carcinomas of the esophagus

Technik und Taktik chirurgischer Eingriffe im Becken bei Rektum- und Kolonkarzinom

German Society of Visceral Surgery

Shigatoxin-B als neuartiger Vektor für das spezifische Tumor-Targeting von kolorektalen Karzinomen und Lebermetastasen