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

Neoadjuvant chemotherapy for locally advanced gastric cancer leads to major histopathological response in less than 30 % of patients. Data on interim endoscopic response assessment do not exist. This exploratory prospective study evaluates early endoscopy after 50 % of the chemotherapy as predictor for later response and prognosis. Forty-seven consecutive patients were included (45 resected; 33 R0 resections). All patients received baseline endoscopy and CT scans, after 50 % of their chemotherapy (EGD-1, CT-1) and after completion of chemotherapy (EGD-2, CT-2). Interim endoscopic response (EGD-1) was assessed after having received 50 % (6 weeks) of the planned 12 weeks of neoadjuvant chemotherapy. Post-chemotherapy response was clinically assessed by a combination of CT scan (CT-2) and endoscopy (EGD-2). Histopathological response was determined by a standardized scoring system (Becker criteria). Endoscopic response was defined as a reduction of >75 % of the tumor mass. Twelve patients were responders at EGD-1 and 13 at EGD-2. Nine patients (19.1 %) were clinical responders and 7 patients (15.6 %) were histopathological responders after chemotherapy. Specificity, accuracy, and negative predictive value of the interim EGD-1 for subsequent histopathological response were 31/38 (82 %), 36/47 (76 %), and 31/33 (93 %); and for recurrence or death, 28/30 (93.3 %), 38/47 (80.9 %), and 28/35 (80.0 %). Response at EGD-1 was significantly associated with histopathological response (p = 0.010), survival (p < 0.001), and recurrence-free survival (p = 0.009). Interim endoscopy after 6 weeks predicts response and prognosis. Therefore, tailoring treatment according to interim endoscopic assessment could be feasible, but the findings of this study should be validated in a larger patient cohort.

/pdf/interim-endoscopy-results-during-neoadjuvant-therapy-for-52mj99bhqm.pdf

Interim endoscopy results during neoadjuvant therapy for gastric cancer correlate with histopathological response and prognosis.

Die laparoskopische Ultraschalluntersuchung (LUS) vergrosert den Informationsgewinn bei der diagnostischen Laparoskopie (DL) durch die Beurteilung der “dritten Dimension”, da des Organinnere und der Retroperitonealraum sichtbar gemacht werden. Die dazu notwendigen technischen Voraussetzungen sind mit der Einfuhrung flexibler Ultraschallsonden, Bildmixingsystemen und dem Dopplermodus gegeben. Beim Magenkarzinom kann die LUS wertvolle Aufschlusse fiber die retrogastrale Ausbreitung, die Vergroserung von Lymphknoten im Bereich der kleinen Kurvatur oder Infiltrationen des Diaphragmas geben. Ebenso werden Lebermetastasen darstellbar, die fur die klassischen bildgebenden Verfahren zu klein sind. In einer eigenen Untersuchungsserie wurde allein durch die sonographische Diagnostik eine Anderung des praoperativen Befundes in 8% der Falle erzielt. Auch die bisher unbefriedigende preoperative Abklarung des fruhen Pankreaskarzinoms konnte durch die Verwendung der LUS verbessert werden. Der Tumor kann exakt lokalisiert und die Invasion von Blutgefasen oder eine lokale oder regionale Lymphknotenmetastasierung mittels LUS konnen beurteilt werden. Beim Speiserohrenkarzinom bzw. Kardiakarzinom kann die LUS zum Ausschlus kleiner Lebermetastasen, einer Zwerchfellinfiltration oder eines abdominellen Lymphknotenbefalls hilfreich sein. Bei Leberprozessen ermoglicht die LUS eine gezielte Dignitatsabklarung durch Punktion. Unter zusdtzlicher Beurteilung des extrahepatischen Lymphknotenstatus ersetzt die LUS eine ansonsten erforderliche diagnostische Laparotomie vor Lebertransplantation. Die heutigen Erfahrungen bestatigen bereits die Rolle der LUS als wertvolle Erweiterung der diagnostischen Laparoskopie, die nicht nur den Informationsgewinn durch DL erweitert, sondern auch zusatzliche Informationen im Vergleich zu konventionellen bildgebenden Verfahren erbringt.

The technique of laparoscopic ultrasound study in diagnostic laparoscopy

The incidence of adenocarcinoma of the distal esophagus is increasing at an alarming rate. Intestinal metaplasia in the distal esophagus, i.e. Barrett’s esophagus, has been identified as the single most important risk factor for these tumors. Barrett’s esophagus develops as a consequence of chronic mucosal injury in up to 10% of patients with long-lasting gastroesophageal reflux disease. Experimental and clinical data indicate that adenocarcinoma of the distal esophagus is a direct consequence of mixed (i.e., acid and bile) reflux into the esophagus. Interestingly, Helicobacter pylori infection of the stomach appears to exert a protective effect against the development of esophageal adenocarcinoma. Neither aggressive medical acid suppression nor antireflux surgery can induce a predictable regression of Barrett’s esophagus or exert a protective effect against its malignant degeneration. Endoscopic ablation of Barrett’s esophagus, although appealing, currently constitutes a potentially dangerous procedure without proven benefit for the patient. Since the development of Barrett’s adenocarcinoma follows a multistep process from metaplasia through increasingly severe grades of dysplasia, close endoscopic surveillance with extensive biopsies currently remains the only means to identify patients at risk for malignant degeneration and detect esophageal adenocarcinoma at an early and curable stage.

Malignant Degeneration of Barrett’s Esophagus: Clinical Point of View

The effect of low-molecular weight (LMW) heparin fragment (one injection of 1500 aPTT [activated partial thromboplastin time]-U/24 h)--group 1--was compared with unfractionated (UF) heparin (3 x 5000 IU/24 h)--group 2--in a randomized prospective double-blind trial of 404 patients (202 patients in each group), aged 50 years or older, undergoing abdominal surgery. The two groups were well matched for thromboembolic risk factors. The first subcutaneous injection was made two hours preoperatively; postoperative injections continued for at least seven days. The radiofibrinogen test served as the test criterion. If positive, phlebography and lung sequence scanning were performed. On complete prophylaxis the thrombosis rate was nearly identical in the two groups--10.8% vs 11.4%. No pulmonary emboli were detected in either group if correctly treated. There was no significant difference between the two groups with respect to peroperative blood loss, re-operation rate and wound haematoma rate. But there was a significantly higher number of injection haematomas in group 2. These results suggest that a single daily injection of 1500 aPTT-U LMW heparin provides effective prophylaxis against postoperative venous thromboembolism.

Thromboembolieprophylaxe mit niedermolekularem Heparin in der Abdominalchirurgie

The fatalistic approach towards surgical therapy of esophageal squamous cell cancer has been replaced in recent years by a more differentiated view. This was triggered by the establishment of individualized therapeutic modalities based on tumor stage, tumor location, general patient status, and comorbidity. Despite advances in nonsurgical therapy of squamous cell esophageal cancer, esophagectomy remains the central therapeutic modality. Primary subtotal en-bloc esophagectomy with lymphadenectomy is the only curative option with a high likelihood of success for resectable tumors (uT1-3 categories) located below the level of the tracheal bifurcation and for early more proximal tumors. In patients with locally advanced tumors at or above the level of the tracheal bifurcation, surgical resection can still cure those who respond to neoadjuvant radiochemotherapy. Preoperative "conditioning" of risk patients, surgical safety strategies in risk situations, and standardization of both the operative procedure and the perioperative management have resulted in a marked reduction of the previously substantial postoperative mortality to below 3% in experienced centers. In our own experience of 900 esophagectomies for squamous cell esophageal cancer, the 5-year survival rate rose from about 20% to more than 50% in the last two decades. Esophagectomy thus has become a safe operation and remains the only therapeutic option offering cure for a substantial proportion of patients with squamous cell cancer of the esophagus.

J. R. Siewert

Papers

Interim endoscopy results during neoadjuvant therapy for gastric cancer correlate with histopathological response and prognosis.

The technique of laparoscopic ultrasound study in diagnostic laparoscopy

Malignant Degeneration of Barrett’s Esophagus: Clinical Point of View

Thromboembolieprophylaxe mit niedermolekularem Heparin in der Abdominalchirurgie

Esophagectomy as therapeutic principle for squamous cell esophageal cancer