M.F. von Meyenfeldt

Extended Lymph-Node Dissection for Gastric Cancer

BACKGROUND Curative resection is the treatment of choice for gastric cancer, but it is unclear whether this operation should include an extended (D2) lymph-node dissection, as recommended by the Japanese medical community, or a limited (D1) dissection. We conducted a randomized trial in 80 Dutch hospitals in which we compared D1 with D2 lymph-node dissection for gastric cancer in terms of morbidity, postoperative mortality, long-term survival, and cumulative risk of relapse after surgery. METHODS Between August 1989 and July 1993, a total of 996 patients entered the study. Of these patients, 711 (380 in the D1 group and 331 in the D2 group) underwent the randomly assigned treatment with curative intent, and 285 received palliative treatment. The procedures for quality control included instruction and supervision in the operating room and monitoring of the pathological results. RESULTS Patients in the D2 group had a significantly higher rate of complications than did those in the D1 group (43 percent vs. 25 percent, P<0.001), more postoperative deaths (10 percent vs. 4 percent, P= 0.004), and longer hospital stays (median, 16 vs. 14 days; P<0.001). Five-year survival rates were similar in the two groups: 45 percent for the D1 group and 47 percent for the D2 group (95 percent confidence interval for the difference, -9.6 percent to +5.6 percent). The patients who had R0 resections (i.e., who had no microscopical evidence of remaining disease), excluding those who died postoperatively, had cumulative risks of relapse at five years of 43 percent with D1 dissection and 37 percent with D2 dissection (95 percent confidence interval for the difference, -2.4 percent to +14.4 percent). CONCLUSIONS Our results in Dutch patients do not support the routine use of D2 lymph-node dissection in patients with gastric cancer.

Randomised comparison of morbidity after D1 and D2 dissection for gastric cancer in 996 Dutch patients

For patients with gastric cancer deemed curable the only treatment option is surgery, but there is disagreement about whether accompanying lymph-node dissection should be limited to the perigastric nodes (D1) or should extend to regional lymph nodes outside the perigastric area (D2). We carried out a multicentre randomised comparison of D1 and D2 dissection. 1078 patients were randomised (539 to each group). 26 allocated D1 and 56 allocated D2 were found not to satisfy eligibility criteria (histologically confirmed adenocarcinoma of the stomach without clinical evidence of distant metastasis). Each of the remainder was attended by one of eleven supervising surgeons who decided whether curative resection was possible and, if so, assisted with the allocated procedure. Among the 711 patients (380 D1, 331 D2) judged to have curable lesions, D2 patients had a higher operative mortality rate than D1 patients (10 vs 4%, p = 0.004) and experienced more complications (43 vs 25%, p < 0.001). They also needed longer postoperative hospital stays (median 25 [range 7-277] vs 18 [7-143] days, p < 0.001). Morbidity and mortality differences persisted in almost all subgroup analyses. While we await survival results, D2 dissection should not be used as standard treatment for western patients.

Accuracy of magnetic resonance imaging in prediction of tumour-free resection margin in rectal cancer surgery

BACKGROUND Incomplete surgical removal of the circumferential tumour spread is believed to be the main cause of local recurrence after resection of rectal cancer. This study assessed the accuracy of magnetic resonance imaging (MRI) with a phased-array coil for preoperative staging and prediction of the distance of the tumour from the circumferential resection margin in a total mesorectal excision. METHODS 76 patients with primary rectal cancer were preoperatively assessed by MRI at 1.5 T, with a phased-array coil. Two observers independently scored, on two occasions, the tumour stage and measured the distance to the mesorectal fascia. Their findings were compared with the final histological findings. FINDINGS The MRI tumour stage agreed with the histological stage in 63 (83%) of 76 patients (weighted kappa=0.77 [95% CI 0.66-0.89]) for observer 1, and in 51 (67%) patients (weighted kappa=0.52 [0.37-0.67]) for observer 2. The intraobserver agreement on the tumour stage was good (kappa=0.80 [0.69-0.91]) for observer 1 but moderate (kappa=0.49 [0.34-0.65]) for observer 2. The interobserver agreement was moderate (kappa=0.53 [0.38-0.69]). In 12 patients with an obvious T4 tumour, a margin of 0 mm was correctly predicted. Of 29 patients for whom the pathologist reported a distance of at least 10 mm without specifying the actual distance, a distance of at least 10 mm was predicted in 28 by observer 1 and 27 by observer 2. For the remaining 35 patients, a regression curve was constructed; from this, a histological distance of at least 1.0 mm can be predicted with high confidence when the measured distance on MRI is at least 5.0 mm. INTERPRETATION MRI with a phased-array coil showed moderate accuracy and reproducibility for predicting the tumour stage of rectal cancers. The clinically more important circumferential resection margin can, however, be predicted with high accuracy and consistency, allowing preoperative identification of patients at risk of recurrence who will benefit from preoperative radiotherapy, more extensive surgery, or both.

Glutamine and the preservation of gut integrity

Parenteral glutamine dipeptide improves nitrogen balance in postoperative patients on total parenteral nutrition (TPM). Animal studies show that the structure and function of the gut is preserved by glutamine. It is not known if this is the case in human beings. 20 patients admitted to hospital for total parenteral nutrition were randomly allocated to receive parenteral nutrition enriched with glycyl-L-glutamine (Gln TPN), or standard parenteral nutrition (STPN). Mucosal biopsy specimens were taken from the second part of the duodenum before starting parenteral nutrition, and after two weeks. The ratio between the urine concentrations of lactulose and mannitol after enteral administration was used to measure intestinal permeability. After two weeks of parenteral nutrition in the GlnTPN group, intestinal permeability was unchanged, whereas permeability in the STPN group increased. Villus height was unaltered in the GlnTPN group but in the STPN group it decreased. The addition of glutamine to parenteral nutrition prevents deterioration of gut permeability and preserves mucosal structure.

Systematic review of enhanced recovery programmes in colonic surgery.

Fast track (FT) programmes optimize perioperative care in an attempt to accelerate recovery, reduce morbidity and shorten hospital stay. The aim of this review was to assess FT programmes for elective segmental colonic resections.

A protocol is not enough to implement an enhanced recovery programme for colorectal resection

Single‐centre studies have suggested that enhanced recovery can be achieved with multimodal perioperative care protocols. This international observational study evaluated the implementation of an enhanced recovery programme in five European centres and examined the determinants affecting recovery and length of hospital stay.

Perioperative nutritional support: a randomised clinical trial

Ever since methods of artificial nutritional support became available, attempts have been made using this form of treatment to reduce mortality and morbidity in surgical patients. Many trials have addressed this question, but very few have given a meaningful answer because of conceptual and methodological flaws. We therefore undertook a prospective randomised trial investigating the effects of at least 10 days pre-operative total parenteral nutrition (TPN) (n = 51) or total enteral nutrition (TEN) (n = 50) providing 150% basal energy expenditure (BEE) non-protein energy, to reduce major postoperative complications and mortality in a homogeneous patient group with signs of depletion. 50 patients served as a depleted control group (D) and 49 patients served as a non-depleted reference group (ND) and were operated upon without delay. Depleted control patients suffered significantly more septic complications than did patients in the non-depleted reference group (p < 0.05). There was no significant difference, however, in septic complications between either of the nutritional support groups and the non-depleted control group. In high risk patients, with weight loss >10% of body weight and over 500 ml blood loss during operation, a significant decrease in major complications was observed (p < 0.05) as a result of nutritional support. We conclude that pre-operative nutritional support, in patients with severe depletion, results in a reduction in major complications to a degree that justifies its routine use in this selected group of patients.

Functional compromise reflected by sarcopenia, frailty, and nutritional depletion predicts adverse postoperative outcome after colorectal cancer surgery

OBJECTIVE To determine the association of sarcopenia with postoperative morbidity and mortality after colorectal surgery. BACKGROUND Functional compromise in elderly colorectal surgical patients is considered as a significant factor of impaired postoperative recovery. Therefore, the predictive value of preoperative functional compromise assessment was investigated. Sarcopenia is a hallmark of functional compromise. METHODS A total of 310 consecutive patients who underwent oncologic colorectal surgery were included in a prospective digital database. Sarcopenia was assessed using the L3 muscle index utilizing Osirix on preoperative computed tomography. Groningen Frailty Indicator and Short Nutritional Assessment Questionnaire scores were used to assess frailty and nutritional compromise. Predictors for anastomotic leakage, sepsis, and mortality were analyzed by logistic regression analysis. RESULTS Age was an independent predictor of mortality [P = 0.04; odds ratio, 1.17; 95% confidence interval (CI), 1.01-1.37]. Thirty-day/in-hospital mortality rate in sarcopenic patients was 8.8% versus 0.7% in nonsarcopenic patients (P = 0.001; odds ratio, 15.5; 95% CI, 2.00-120). Sarcopenia was not predictive for anastomotic leakage or sepsis. Combination of high Short Nutritional Assessment Questionnaire score, high Groningen Frailty Indicator score, and sarcopenia strongly predicted sepsis (P = 0.001; odds ratio, 25.1; 95% CI, 5.11-123), sensitivity, 46%; specificity, 97%; positive likelihood ratio, 13 (95% CI, 4.4-38); negative likelihood ratio, 0.57 (95% CI, 0.33-0.97). CONCLUSIONS Functional compromise in colorectal cancer surgery is associated with adverse postoperative outcome. Assessment of functional compromise by means of a nutritional questionnaire (Short Nutritional Assessment Questionnaire), a frailty questionnaire (Groningen Frailty Indicator), and sarcopenia measurement (L3 muscle index) can accurately predict postoperative sepsis.

Citrulline: A physiologic marker enabling quantitation and monitoring of epithelial radiation-induced small bowel damage

PURPOSE Small bowel irradiation results in epithelial cell loss and consequently impairs function and metabolism. We investigated whether citrulline, a metabolic end product of small bowel enterocytes, can be used for quantifying radiation-induced epithelial cell loss. METHODS AND MATERIALS NMRI mice were subjected to single-dose whole body irradiation (WBI). The time course of citrullinemia was assessed up to 11 days after WBI. A dose-response relationship was determined at 84 h after WBI. In addition, citrullinemia was correlated with morphologic parameters at this time point and used to calculate the dose-modifying factor (DMF) of glutamine and amifostine on acute small bowel radiation damage. RESULTS After WBI, a time- and dose-dependent decrease in plasma citrulline level was observed with a significant dose-response relationship at 84 h. At this time point, citrullinemia significantly correlated with jejunal crypt regeneration (p < 0.001) and epithelial surface lining (p = 0.001). A DMF of 1.0 and 1.5 was computed at the effective dose 50 (ED50) level for glutamine and amifostine, respectively. CONCLUSIONS Citrullinemia can be used to quantify acute small bowel epithelial radiation damage after single-dose WBI. Radiation-induced changes in citrullinemia are most pronounced at 3 1/2 to 4 days postirradiation. At this time point, citrullinemia correlates with morphologic endpoints for epithelial radiation damage.

Gut permeability, intestinal morphology, and nutritional depletion.

Nutritional depletion increases the risk for postoperative complications. The intestinal barrier may be important in the underlying pathophysiologic mechanism. In this study, 26 patients were evaluated to determine whether nutritional depletion was related to gut integrity and intestinal morphology. Nutritional depletion was estimated by calculating percentage ideal body weight (PIB) or percentage ideal fat free mass (PIFFM). To assess gut integrity, a lactulose/mannitol (L/M) test was performed. Duodenal biopsies were taken, and villous height, crypt depth, number of IgA-producing plasma cells, intraepithelial lymphocytes (IELs), and proliferating index were determined. The L/M ratio was increased, and villous height was decreased in depleted patients. Depletion was not associated with differences in the number of immune cells or proliferating index. The number of IgA-producing plasma cells was positively correlated with the L/M ratio. This study shows that nutritional depletion is associated with increased intestinal permeability and a decrease in villous height.