When diseased intestine (i.e., from colon cancer, diverticulitis) requires resection, its reconnection (termed anastomosis) can be complicated by non-healing of the newly joined intestine resulting in spillage of intestinal contents into the abdominal cavity (termed anastomotic leakage). While it is suspected that the intestinal microbiota have the capacity to both accelerate and complicate anastomotic healing, the associated genotypes and functions have not been characterized. Using 16S rRNA amplicon sequencing of samples collected on the day of surgery (postoperative day 0 (POD0)) and the 6th day following surgery (postoperative day 0 (POD6)), we analyzed the changes in luminal versus tissue-associated microbiota at anastomotic sites created in the colon of rats. Results indicated that anastomotic injury induced significant changes in the anastomotic tissue-associated microbiota with minimal differences in the luminal microbiota. The most striking difference was a 500-fold and 200-fold increase in the relative abundance of Enterococcus and Escherichia/Shigella, respectively. Functional profiling predicted the predominance of bacterial virulence-associated pathways in post-anastomotic tissues, including production of hemolysin, cytolethal toxins, fimbriae, invasins, cytotoxic necrotizing factors, and coccolysin. Taken together, our results suggest that compositional and functional changes accompany anastomotic tissues and may potentially accelerate or complicate anastomotic healing.

/pdf/intestinal-anastomotic-injury-alters-spatially-defined-c2f59gm2xw.pdf

Intestinal anastomotic injury alters spatially defined microbiome composition and function

The outcome and quality of surgical treatment in gastric cancer are closely associated with specific postoperative morbidity and mortality, in addition to an oncosurgically adequate resection status. In this context, a preventive concept of decreasing the insufficiency rate of esophageal anastomosis may have a great impact. Over a time period of 12 months (from 1 January 2002 to 31 December 2002), 1,199 patients (from 80 East German hospitals) with gastric carcinoma, carcinoma of the esophagogastral junction, or gastrointestinal stroma tumor (GIST) were enrolled in this prospective multicenter observational study with the aim of evaluating their early postoperative outcome. By means of a logistic regression analysis, independent variables, which alter significantly the healing of esophagojejunal anastomosis, were determined; in addition, their clinical impact on preventive management to lower the insufficiency rate of esophageal anastomosis was investigated. In 1,139 patients, histological investigation revealed gastric carcinoma. Out of these patients, 1,031 subjects underwent surgical intervention (90.5%) and 891 individuals underwent resection (86.4%). In 813 patients, radical resection (subtotal resection and gastrectomy) was executed (78.9%), whereas in 726 cases, R0 resection was achieved (81.5%). Gastrectomy was the preferred procedure in 649 patients, resulting in a gastrectomy rate of 62.9% relating to all patients who underwent operation (curative and palliative intention, 80.3% and 19.7%, respectively). The insufficiency rate of esophagojejunal anastomosis was 5.7% (37/649). Neither the comparison between the various procedures for the reconstruction of the esophagojejunal passage and anastomosing techniques after gastrectomy nor that between gastrectomies with curative and palliative intention revealed any significant difference. Dysphagia and gastric outlet syndrome due to a stenosis were determined as independent variables by a logistic regression analysis of all preoperative and intraoperative variables. In all patients with gastric carcinoma, both parameters were recorded in 9.9% (113/1,139) and 6.7% (76/1,139), respectively. Dysphagia and gastric stenosis, which significantly influence the healing of esophagojejunal anastomosis after gastrectomy, are considered characteristics of an advanced tumor growth and a pretherapeutic lack of an adequate nutrition. This emphasizes the necessity of an early diagnosis of gastric cancer in order to lower perioperative morbidity. In addition, dysphagia is commonly associated with an obstruction of the upper gastrointestinal tract, which can lead to nutritional deficits, and thus deserves specific care during preventive management.

Insufficiency risk of esophagojejunal anastomosis after total abdominal gastrectomy for gastric carcinoma.

Background: Worldwide, almost one million new cases of stomach cancer were diagnosed in 2012, making it the fifth most common cancer, and the third leading cause of cancer deaths. The current tumor node metastasis (TNM) staging system represents a consensus between the East and the West, and will serve as a strong foundation upon which to build future evidence. In this review article, we first discuss the definition and optimal surgery for locally advanced gastric cancer, followed by the general principles when considering a pre vs . postoperative radiotherapy (RT) strategy. We then provide a synthesis of the existing randomized trial evidence in an attempt clarify the role of pre and postoperative RT in the management of locally advanced gastric cancer.
 Methods: A Medline search 1966-Jun 2014 was undertaken. Randomized trials including patients with locally advanced gastric cancer (using established definitions), comparing RT [with or without chemotherapy (CT)], with surgery alone or other treatment modalities were included. Systematic reviews and evidence based practice guidelines that include this body of primary studies were preferentially discussed. Medline, Cochrane Library, Clinicaltrial.gov, Guidelines Clearinghouse were searched.
 Results: Sixteen randomized trials, three systematic reviews and one practice guideline were included as the evidence base. In this group of studies, two reports compared postoperative chemoradiotherapy (CRT) with surgery alone. Driven predominantly by INT0116, they established the role of postoperative CRT to provide a survival benefit in a patient group that underwent surgery with predominantly D0-1 dissections. Preoperative RT (four studies) showed promise for survival benefit but the risks of bias in these trials were high. Postoperative CRT compared with CT alone (eight trials) showed no survival benefit with the addition of radiation although some evidence of activity can be observed with improved local regional control.
 Conclusions and future directions: Technical expertise to enable the delivery of high quality RT to complex target volumes as is required in gastric cancer, and surgical standards to ensure the delivery of high quality surgery, have matured in recent years. Six trials with large sample sizes are currently ongoing to better define the role of preoperative CRT (two studies) and postoperative CRT (four studies), when used in conjunction with high quality surgery and RT, and contemporary CT regimens. The moderate likelihood of locoregional recurrences and the favorable therapeutic ratio with using RT preoperatively in other settings, provide optimism that preoperative CRT would have a pivotal role to play in locally advanced gastric cancer. Active accrual into ongoing trials is strongly encouraged.

/pdf/postoperative-chemoradiotherapy-vs-preoperative-8l2m4fz041.pdf

Postoperative chemoradiotherapy vs . preoperative chemoradiotherapy for locally advanced (operable) gastric cancer: clarifying the role and technique of radiotherapy

Purpose We retrospectively analyzed the impact of intraoperative radiation therapy (IORT) on long-term survival in patients with resectable gastric cancer. Methods and Materials From 1991 to 2001, a total of 84 patients with gastric neoplasms underwent gastectomy or subtotal resection with IORT (23 Gy, 6–15 MeV; IORT-positive [IORT + ] group). Patients with a history of additional neoadjuvant chemotherapy, histologically confirmed R1 or R2 resection, or reoperation with curative intention after local recurrence were excluded from further analysis. The remaining 61 patients were retrospectively matched with 61 patients without IORT (IORT-negative [IORT − ] group) for Union Internationale Contre le Cancer (UICC) stage, patient age, histologic grading, extent of surgery, and level of lymph node dissection. Subgroups included postoperative UICC Stages I ( n = 31), II ( n = 11), III ( n = 14), and IV ( n = 5). Results Mean follow-up was 4.8 years in the IORT + group and 5.0 years in the IORT − group. The overall 5-year patient survival rate was 58% in the IORT + group vs. 59% in the IORT − group ( p = 0.99). Subgroup analysis showed no impact of IORT on 5-year patient survival for those with UICC Stages I/II (76% vs. 80%; p = 0.87) and III/IV (21% vs. 14%, IORT + vs. IORT − group; p = 0.30). Perioperative mortality rates were 4.9% and 4.9% in the IORT + vs. IORT − group. Total surgical complications were more common in the IORT + than IORT − group (44.3% vs. 19.7%; p + group. Conclusions Use of IORT was associated with low locoregional tumor recurrence, but had no benefit on long-term survival while significantly increasing surgical morbidity in patients with curable gastric cancer.

Long-term results after intraoperative radiation therapy for gastric cancer.

Pattern of failures in gastric cancer patients with lymph node involvement treated by surgery, intraoperative and external beam radiotherapy.

UNLABELLED It was the aim of the study to find by retrospective analysis of data from totally gastrectomized patients risk factors for the development of esophago-jejunal anastomotic leakage, that may be avoidable or influenced therapeutically. PATIENTS AND METHODS The study design was retrospective involving 838 patients with total gastrectomy for gastric cancer from the years 1973-1993. In 134 cases leakage of the esophago-jejunostomy occurred. The relative risk for the development of leakage associated with individual parameters was determined by comparing the data from 704 patients without leakage to the data from 134 patients presenting with this complication. For a subgroup of 86 patients with anastomotic leakage microbiological data of swabs taken from the anastomoses were available, which were evaluated with respect to potentially pathogenic bacilli. RESULTS The overall leakage rate of esophago-jejunal anastomoses was 15.9% (n = 134). The mortality rate during this time period amounted to 14.3%. Leakage was a most highly significant factor for mortality (p = 0.0001). Significant risk factors for leakage of the esophago-jejunostomy were tumors of the cardia, splenectomy, a duration of operating time of more than 5 hours and manual suture technique compared to stapler anastomoses. Tumor unrelated associated disease, tumor stage and a history of other preexisting gastric diseases were not associated with an increased relative risk. At the time of the initial clinical manifestation of leakage the following pathogenic bacilli could be isolated from leaking anastomoses with decreasing incidence: E. coli, S. aureus, Proteus mirabilis, Pseudomonas aeruginosa, Klebsiella pneumoniae a.o. The bacterial spectrum has not changed during the observation period of 20 years. SUMMARY With the exception of the choice of suture techniques the identified clinical risk factors cannot be avoided or influenced therapeutically due to a lack of potentially curative treatment alternatives. In contrast potentially pathogenic bacilli associated with leakage can be prevented from coming in contact with anastomoses thereby preventing infection and leakage.

Risk factors and pathogenic microorganisms in patients with insufficient esophagojejunostomy after gastrectomy

In order to evaluate the role of adjuvant IORT in the treatment of resectable gastric carcinoma, we carried out a randomized trial comparing surgery and surgery+adjuvant IORT. The study included 115 patients within a 74-month period, 51 of them received a single application of 28 Gy to the celiac axis. Patients were comparable with regard to age, sex, tumor stage and operative morbidity. The difference in mean survival time (IORT: 26.9 months vs. non-IORT, 30.8 months) and tumor-related death in the long-term course (mean follow-up period 29.2 months) with 29.4% (15/51) in the IORT-treated patients vs. 31.2% (20/64) in non-irradiated patients did not reach significance.

Adjuvant intraoperative radiotherapy of stomach carcinoma

Early Results of IORT in the Treatment of Gastric Cancer

In order to evaluate the role of adjuvant IORT in the treatment of resectable gastric carcinoma, we carried out a randomized trial comparing surgery and surgery + adjuvant IORT. The study included 115 patients within a 74-month period, 51 of them received a single application of 28 Gy to the celiac axis. Patients were comparable with regard to age, sex, tumor stage and operative morbidity. The difference in mean survival time (IORT: 26.9 months vs. non-IORT: 30.8 months) and tumor-related death in the long-term course (mean follow-up period 29.2 months) with 29.4% (15/51) in the IORT-treated patients vs. 31.2% (20/64) in non-irradiated patients did not reach significance.

Adjuvante intraoperative Strahlentherapie (IORT) beim Magenkarzinom

Risikofaktoren und pathogene mikroorganismen bei patienten mit insuffizienter osophago-jejunostomie nach gastrektomie

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