Yutaka J. Kawamura

Assessment for frailty is useful for predicting morbidity in elderly patients undergoing colorectal cancer resection whose comorbidities are already optimized

BACKGROUND The clinical syndrome of frailty identified through the assessment of weight loss, gait speed, grip strength, physical activity, and physical exhaustion has been used to identify patients with reduced reserves. We hypothesized that frailty is useful in predicting adverse outcomes in optimized elective elderly colorectal surgery patients. METHODS A prospective study was conducted at 2 centers (Singapore and Japan). All patients over 75 years of age undergoing colorectal resection were assessed for the presence of the syndrome of frailty. All these patients had already had their comorbidities optimized for surgery. The outcome measure was postoperative major complications (defined as Clavien-Dindo type II and above complications). RESULTS Eighty-three patients were studied from February 2008 to April 2010. The mean age was 81.5 years (range 75-93 years). The mean comorbidity index was 3.37 (range 0-11). Twenty-six (31.3%) patients were an American Society of Anesthesiologists (ASA) score of 3 and above. Chi-square analysis revealed that the odds ratio of postoperative major complications was 4.083 (95% confidence interval, 1.433-11.638) when the patient satisfied the criteria for frailty. Albumin <35, ASA >3, comorbidity index >5, and Physiologic and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) scores were not predictive of postoperative major complications. CONCLUSIONS Preliminary findings show that frailty is a potent adjunctive tool of predicting postoperative morbidity. Frailty can be used to identify elderly patients needing further optimization before major surgery.

Predictive factors for lymph node metastasis in T1 stage colorectal carcinomas.

PurposeSelective endoscopie resection may cure early colorectal cancer (Tl), but the management is controversial. There is concern about the small risk of lymph node metastasis, which will not be treated by endoscopie resection alone. The authors sought predictive markers of lymph node metastasis to assist patient management. METHODS: The authors retrospectively analyzed consecutive cases of Tl stage colorectal cancer resected using endoscopie resection or bowel surgery over the period 1979 to 2000. The risk of lymph node metastasis was analyzed using logistic regression model for the markers selected by univariate analysis: the type of initial treatment, depth of submucosal invasion, lymphatic channel invasion, differentiation of histology, and invasive front histology. RESULTS: Two hundred seventy-eight patients were available for study. Twenty-one had lymph node metastasis. Depth of submucosal invasion (2 2,000 yum) and lymphatic channel invasion significantly predicted risk of lymph node metastasis in multivariate analysis. When these two factors were adopted for the prediction of lymph node metastasis, sensitivity, specificity, positive predictive value, and negative predictive value were 100, 55.6, 15.6, and 100 percent, respectively. CONCLUSIONS: Depth of submucosal invasion and lymphatic channel invasion were accurate predictive factors for lymph node metastasis. These two factors could be used in selecting appropriate cases for surgery after endoscopie resection.

Interleukin-6 and stress hormone responses after uncomplicated gasless laparoscopic-assisted and open sigmoid colectomy

PURPOSE: Laparoscopic colectomy has increasingly been advocated as an option for treatment of colonic disease. The purpose of this study was to compare effects of laparoscopicassisted sigmoid colectomy (LAS) and conventional open colectomy (OPEN) on postoperative cytokine and stress hormone responses. METHODS: Fourteen patients with sigmoid colon cancer, apparently free of preoperative complications, were analyzed. Patients in both groups underwent sigmoid colectomy with lymphadenectomy. LAS was performed by the gasless abdominal wall-lifting method. A 5 cm incision was placed at the beginning of the operation. Blood samples were taken preoperatively and postoperatively for measurement of interleukin-6, glucagon and C-reactive protein. Urinary catecholamine excretions were also determined postoperatively. RESULTS: The two groups of patients were similar with respect to age (61±7 for LASvs.64±9 for OPEN) and sex. Intraoperative blood loss did not differ significantly between groups (112±97 ml for LASvs.366±380 ml for OPEN). Operative times for LAS tended to be longer than those for OPEN (231±67vs.169±45 minutes;P=0.08). Similar time courses of postoperative interleukin-6, C-reactive protein, and stress hormone responses were observed in both groups. No significant differences were observed in the magnitude of changes except that the serum interleukin-6 level on day of surgery (postoperative day 0) was significantly higher in LAS patients than in those receiving OPEN. In addition, interleukin-6 levels showed a significant positive correlation with operative duration (r=0.582;P<0.05). CONCLUSIONS: Data suggest that stress responses after sigmoid colectomy, in patients undergoing LAS, are comparable with those of patients receiving OPEN and that the early interleukin-6 response after surgery appears to be associated with operative time.

Interleukin-13 Damages Intestinal Mucosa via TWEAK and Fn14 in Mice—A Pathway Associated With Ulcerative Colitis

BACKGROUND & AIMS TWEAK, a member of the tumor necrosis factor (TNF) superfamily, promotes intestinal epithelial cell injury and signals through the receptor Fn14 following irradiation-induced tissue damage and during development of colitis in mice. Interleukin (IL)-13, an effector of tissue damage in similar models, has been associated with the pathogenesis of ulcerative colitis (UC). We investigated interactions between TWEAK and IL-13 following mucosal damage in mice. METHODS We compared patterns of gene expression in intestinal tissues from wild-type and TWEAK knockout mice following γ-irradiation. Intestinal explants from these mice were used to detect cell damage induced by IL-13 and TNF-α. Levels of messenger RNA for IL-13, TWEAK, and Fn14 were measured in mucosal samples from patients with UC. RESULTS Based on gene expression analysis, TWEAK mediates γ-irradiation-induced epithelial cell cycle arrest and apoptosis. However, TWEAK alone did not induce damage or apoptosis of primary intestinal epithelial cells. On the other hand, exogenous IL-13 activated caspase-3 in naïve intestinal explants; this process required TWEAK, Fn14, and secretion of endogenous TNF-α which was mediated by ADAM17. Conversely, activation of caspase by exogenous TNF-α required IL-13, TWEAK, and Fn14. In mucosa from patients with UC, messenger RNA levels of IL-13, TWEAK, and Fn14 increased with level of disease severity. CONCLUSIONS IL-13-induced damage of intestinal epithelial cells requires TWEAK, its receptor (Fn14), and TNF-α. IL-13, TNF-α, TWEAK, and Fn14 could perpetuate and aggravate intestinal inflammation in patients with UC.

Pelvic drainage for anterior resection revisited: use of drains in anastomotic leaks.

Background:  Although routine pelvic drainage in colorectal surgery has not been justified in randomized controlled trials, nevertheless, many surgical institutes routinely use pelvic drains after anterior resection. Some reports have focused mainly on the effect of a pelvic drain on anastomotic complications. The purpose of this study was to assess the effectiveness of pelvic drainage in the management of anastomotic leak following anterior resection.

Pathological Predictors for Lymph Node Metastasis in T1 Colorectal Cancer

PurposeTo clarify pathological predictor for lymph node metastasis in T1 colorectal cancer.MethodsOne hundred and sixty-four patients who underwent surgery for single T1 colorectal cancer were reviewed. The pathological differentiations of non-well differentiation, invasion depth (≥2 000 μm), lymphatic channel involvement, venous invasion, and tumor budding were selected as candidate predictors. Tumor budding was estimated according to the definition proposed by Ueno et al. (Gastroenterology 2004; 127:385–394). The lymph node status was set for the endpoint. Logistic regression model was applied to analyze the predictors.ResultsLymph node involvement was observed in 9.8%. The positive rates were 13.4% for the pathological differentiations of non-well differentiation, 51.8% for invasion depth (≥2 000 μm), 6.1% for lymphatic channel involvement, 8.5% for venous invasion, and 14.6% for tumor budding. The pathological differentiations of non-well differentiation (P < 0.001) and tumor budding (P = 0.002) were significantly associated with lymph node metastasis in multivariate analysis. When either two significant factors was adopted for the prediction of the lymph node metastasis, the sensitivity, specificity, positive predictive value, and negative predictive value were 94%, 82%, 36%, and 99%, respectively.ConclusionThe pathological differentiations of non-well differentiation and tumor budding are useful predictors for lymph node metastasis in T1 colorectal cancer.

Effect of high ligation on the long-term result of patients with operable colon cancer, particularly those with limited nodal involvement

OBJECTIVE To find out what effect the extent of nodal dissection has on patients with operable colonic cancer. DESIGN Retrospective study. SETTING Teaching hospital, Japan. PATIENTS 564 consecutive patients who had potentially curative operations for colon cancer. Patients treated by limited nodal dissection, in which only pericolonic nodes were dissected, were excluded. MAIN OUTCOME MEASURES Disease free survival classified by extent of nodal dissection. RESULTS High ligation gave no significant advantage when patients were subgrouped according to degree of nodal involvement. However, number of patients with aggressive involvement (including intermediate or central nodes) was small. 511 patients (91%) had limited nodal involvement (no nodal involvement or nodal involvement confined to pericolonic nodes). High ligation of the vessels gave no advantage even with meticulous subgrouping according to age, site, and depth of invasion. CONCLUSION Most patients with colonic cancer had limited nodal involvement. High ligation did not affect the long term results in these patients, so, less invasive low ligation should be considered. A larger study will be necessary to clarify the indications for low and high ligation for patients with aggressive nodal involvement.

Distribution of the first metastatic lymph node in colon cancer and its clinical significance

Introduction  The pattern of distribution of lymph node metastasis in resected specimens of colon cancer has been rarely reported in the English literature. The aim of this study was to determine the location of the first metastatic lymph node, giving insight into the drainage pattern of colon cancer lymphatics.

Distribution of lymph node metastasis in T1 sigmoid colon carcinoma: should we ligate the inferior mesenteric artery?

Objective In standard oncological sigmoid colectomy, the inferior mesenteric artery is ligated either at its origin or at the level of the left colic artery. However, in patients with early-stage carcinoma, the distribution of metastatic nodes may be limited. The aim of this study was to clarify the prevalence and distribution of lymph node metastasis in T1 sigmoid colon carcinoma and to determine the adequate range of lymph node dissection. Material and methods The study included 121 consecutive patients treated for T1 sigmoid colon carcinoma. Clinicopathologic factors associated with nodal metastasis and the distribution of metastatic nodes were analyzed. Results Conclusions Of 121 patients, 12 (10%) had nodal involvement. The depth of invasion and the presence of lymphatic and vascular invasion were significantly associated with nodal metastasis. Of these 12 patients, 11 (92%) had lymph node metastasis confined to pericolic nodes. Nodes along the sigmoidal artery were involved in one patient. There was no involved node along the superior rectal artery or at the root of the inferior mesenteric artery. Lymph node dissection for T1 sigmoid colon carcinoma should be limited to the root of the sigmoidal artery, and the inferior mesenteric artery should be preserved.

Promoter hypermethylation of tumor-related genes in peritoneal lavage and the prognosis of patients with colorectal cancer

The predictive value of free cancer cells in the peritoneal fluid of patients with colorectal cancer (CRC) remain to be elucidated. The aim of this study was to determine the prognostic relevance of the methylation of tumor‐related genes detected in the peritoneal lavage fluid (PLF) of patients undergoing a resection for CRC.