Resistant starch (RS) is starch and products of its small intestinal digestion that enter the large bowel. It occurs for various reasons including chemical structure, cooking of food, chemical modification, and food mastication. Human colonic bacteria ferment RS and nonstarch polysaccharides (NSP; major components of dietary fiber) to short-chain fatty acids (SCFA), mainly acetate, propionate, and butyrate. SCFA stimulate colonic blood flow and fluid and electrolyte uptake. Butyrate is a preferred substrate for colonocytes and appears to promote a normal phenotype in these cells. Fermentation of some RS types favors butyrate production. Measurement of colonic fermentation in humans is difficult, and indirect measures (e.g., fecal samples) or animal models have been used. Of the latter, rodents appear to be of limited value, and pigs or dogs are preferable. RS is less effective than NSP in stool bulking, but epidemiological data suggest that it is more protective against colorectal cancer, possibly via butyrate. RS is a prebiotic, but knowledge of its other interactions with the microflora is limited. The contribution of RS to fermentation and colonic physiology seems to be greater than that of NSP. However, the lack of a generally accepted analytical procedure that accommodates the major influences on RS means this is yet to be established.

Short-Chain Fatty Acids and Human Colonic Function: Roles of Resistant Starch and Nonstarch Polysaccharides

PURPOSE: Preoperative chemoradiation reduces tumor size and nodal metastasis in patients with rectal cancer. Tumor downstaging has been associated with an increased probability of a sphincter-saving procedure and with improved local control. However, pathologic complete response to chemoradiation has not been correlated with local control and patient survival. We studied the prognostic value of pathologic complete response to preoperative chemoradiation in rectal cancer patients. METHODS: We have prospectively followed up 168 consecutive patients with ultrasound Stages II (46) and III (122) rectal cancer treated by preoperative chemoradiation followed by radical resection with mesorectal excision; 161 had a curative resection. Recurrence and survival were compared with tumor characteristics and pathologic complete response. Average follow-up was 37 months. RESULTS: Tumor downstaging occurred in 97 (58 percent) patients, including 21 (13 percent) patients who had a pathologic complete response. None of the clinical or pathologic variables was associated with pathologic complete response. The estimated 5-year rate of local recurrence was 5 percent; of distant metastasis, 14 percent. None of the patients with pathologic complete response has developed disease recurrence. We found no difference in survival among patients with pathologic Stages I, II, or III tumors. CONCLUSIONS: A pathologic complete response to preoperative chemoradiation is associated with improved local control and patient survival. For patients without pathologic complete response, the pathology stage does not have prognostic significance.

A pathologic complete response to preoperative chemoradiation is associated with lower local recurrence and improved survival in rectal cancer patients treated by mesorectal excision.

Purpose The purpose of this study was to examine the impact of the number of negative lymph nodes on survival in patients with stage III colon cancer. Patients and Methods Patients who underwent surgery for stage III colon cancer between January 1988 and December 1997 were identified from the Surveillance, Epidemiology and End Results cancer registry. The number of negative and positive nodes was determined for 20,702 eligible patients. Disease-specific survival was examined by substage according to the number of negative nodes identified. A proportional hazards model was constructed to determine the effect of the number of negative nodes on survival. Results For stage IIIB and IIIC patients, there was a significant decrease in disease-specific mortality as the number of negative nodes increased; cumulative 5-year cancer mortality was 27% in stage IIIB patients with 13 or more negative nodes identified versus 45% in those with three or fewer negative lymph nodes evaluated (P < .0001). In patients with sta...

Increasing negative lymph node count is independently associated with improved long-term survival in stage IIIB and IIIC colon cancer.

Summary Background Mesorectal excision is the international standard surgical procedure for lower rectal cancer. However, lateral pelvic lymph node metastasis occasionally occurs in patients with clinical stage II or stage III rectal cancer, and therefore mesorectal excision with lateral lymph node dissection is the standard procedure in Japan. We did a randomised controlled trial to confirm that the results of mesorectal excision alone are not inferior to those of mesorectal excision with lateral lymph node dissection. Methods This study was undertaken at 33 major hospitals in Japan. Eligibility criteria included histologically proven rectal cancer of clinical stage II or stage III, with the main lesion located in the rectum with the lower margin below the peritoneal reflection, and no lateral pelvic lymph node enlargement. After surgeons had confirmed macroscopic R0 resection by mesorectal excision, patients were intraoperatively randomised to mesorectal excision alone or with lateral lymph node dissection. The groups were balanced by a minimisation method according to clinical N staging (N0 or N1, 2), sex, and institution. Allocated procedure was not masked to investigators or patients. This study is now in the follow-up stage. The primary endpoint is relapse-free survival and will be reported after the primary analysis planned for 2015. Here, we compare operation time, blood loss, postoperative morbidity (grade 3 or 4), and hospital mortality between the two groups. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00190541. Findings 351 patients were randomly assigned to mesoretcal excision with lateral lymph node dissection and 350 to mesorectal excision alone, between June 11, 2003, and Aug 6, 2010. One patient in the mesorectal excision alone group underwent lateral lymph node dissection, but was analysed in their assigned group. Operation time was significantly longer in the mesorectal excision with lateral lymph node dissection group (median 360 min, IQR 296–429) than in the mesorectal excision alone group (254 min, 210–307, p vs 13 [5%] in the mesorectal excision alone group; p=0·46). One patient in the mesorectal excision with lateral lymph node dissection group died of anastomotic leakage followed by sepsis. Interpretation Mesorectal excision with lateral lymph node dissection required a significantly longer operation time and resulted in significantly greater blood loss than mesorectal excision alone. The primary analysis will help to show whether or not mesorectal excision alone is non-inferior to mesorectal excision with lateral lymph node dissection. Funding National Cancer Center, Ministry of Health, Labour and Welfare of Japan.

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(12)70158-4.pdf

Postoperative morbidity and mortality after mesorectal excision with and without lateral lymph node dissection for clinical stage II or stage III lower rectal cancer (JCOG0212): results from a multicentre, randomised controlled, non-inferiority trial.

Surgical site infection (SSI) is the most frequent nosocomial infection among surgical patients, accounting for 38% of all such infections.1,2 It increases medical costs, prolongs hospital stay, and occasionally leads to mortality.1,3,4 Nationwide SSI surveillance has been conducted in more than 300 hospitals in the United States since the establishment of the National Nosocomial Infection Surveillance (NNIS) system in 1970 and, as a result, an enormous amount of data has been accumulated.5

In colorectal surgery, in particular, SSI is a frequent cause of morbidity with an incidence of up to 30% in previous studies.6–10 The NNIS system categorizes all colorectal surgeries into the same “COLO” group, and the SSI rates within this group are stratified according to the NNIS risk index, which consists of the following three factors: an American Society of Anesthesiologists (ASA) score of 3, 4, or 5; a wound classification of contaminated or dirty-infected; and duration of operation lasting more than 3 hours.5 However, previous studies have suggested that SSI rates might not be the same in colon and rectal surgery.11,12 Surgery for rectal cancer is often associated with ostomy formation, preoperative radiation and total mesorectal excision (TME) with anastomosis close to the anal verge, all of which could lead to surgery that lasts longer and has greater bacterial contamination.13–15,16 Therefore, rectal surgery might have a higher risk for developing SSI. Furthermore, the NNIS risk index has been criticized as being unsuitable for risk evaluation in elective colorectal surgery because most patients undergoing such a procedure have an ASA score of 1 or 2 and a wound classification of clean-contaminated.10,16,17 The risk factors for colon and rectal procedures developing SSI may differ, and risk factors that are more specific to each procedure would be more predictive.

In an attempt to clarify the difference between colon and rectal surgery with regard to SSI, we started a prospective SSI surveillance program in a department specializing in colorectal surgery at a university hospital in Japan. The aim of this study was: 1) to determine the actual incidence of incisional SSI in elective colon and rectal surgery, and 2) to identify the risk factors for developing incisional SSIs in these two procedures.

Elective colon and rectal surgery differ in risk factors for wound infection: results of prospective surveillance.

PURPOSE: The effectiveness of preoperative radiation therapy for advanced lower rectal carcinoma to preserve the function of pelvic organs and reduce local recurrences was examined in a prospective, randomized, controlled study. METHODS: Fifty-one patients with a diagnosis of localized and resectable adenocarcinoma of the lower rectum undergoing 50 Gy of preoperative radiotherapy were recruited into the trial between April 1993 and March 1995. The patients were randomly allocated to complete autonomic nerve-preserving surgery without lateral node dissection (D1), or surgery with dissection of the lateral lymph nodes including autonomic nerves (D2) followed by oral administration of carmofur for one year. RESULTS: No difference was observed in either survival or disease-free survival between D1 and D2 groups. There was no difference between the two groups in terms of recurrence rate. A significant difference was observed in urinary and sexual function (P= 0.02 and 0.02, respectively) one year after surgery between D1 and D2 groups. CONCLUSION: This study suggests that lateral node dissection is not necessary in terms of curability for patients with advanced carcinoma of the lower rectum who undergo preoperative radiotherapy.

Randomized, controlled trial of lateral node dissection vs. nerve-preserving resection in patients with rectal cancer after preoperative radiotherapy.

Extended lymphadenectomy and preoperative radiotherapy for lower rectal cancers.

BACKGROUND: Recent studies showed that p53 and p21 may play major roles in determining tumor radiosensitivity through the apoptosis pathway. The aim of this study was to investigate the predicting value of radiosensitivity in human rectal carcinoma. METHODS: p53 and p21/WAF1 expressions in formalin fixed, paraffin-embedded, preradiation biopsy samples from 49 patients with primary rectal carcinoma were analyzed immunohistochemically. p53 and p21 expressions and their relationships with histopathologic changes after radiation and other clinical features were evaluated. RESULTS: Expressions of p53 and p21/WAF1 were 49 and 28.6 percent, respectively. In 36.7 percent of total tumors, significant histopathologic effect can be observed. There was a significant inverse expression of p53 and p21. Most of the p53(+) or p21(−) tumors were radioresistant, and the majority of p53(−) or p21(+) tumors were radiosensitive. Tumors size in the radiosensitive, p53(−), or p21(+) group decreased more significantly than in radioresistant, p53(+), or p21(−) group (P<0.01), and patients with radioresistant, p53(+), or p21(−) tumors had more local recurrence, more distant metastasis, and a shorter five-year survival rate than those with radiosensitive, p53(−), or p21(+) tumors, but without statistic significance. No statistically significant correlation can be observed between other tumor clinical features and radiosensitivity, p53, or p21 expressions. CONCLUSION: Immunohistochemistry detection of p53 and p21 expressions may be useful parameters for more radiosensitive patients selected for preoperative radiotherapy.

Role of p53 and p21/WAF1 detection in patient selection for preoperative radiotherapy in rectal cancer patients.

The major operative indication for ulcerative colitis is intractability. Although steroid side effects appear to be closely associated with surgical indications for intractable ulcerative colitis, this relationship has yet to be analyzed in detail. To elucidate this relationship, we investigated 39 surgical patients with intractable ulcerative colitis, as defined by the Research Committee for Intractable Diseases of the Ministry of Health and welfare of Japan, and 66 conservatively treated patients with ulcerative colitis, of whom 6 had intractable disease. All patients with major steroid side effects and 17/24 (71%) patients with minor side effects underwent surgery. The median number of admissions was higher in patients with major side effects than in those with less severe or no side effects in the operative series, while this value was lower in the non-operative series than in the operative series. This tendency was similar for the total duration of hospitalization and the number of relapses. In the operative series, markedly higher steroid doses were administered to patients with side effects than to those without, and lower doses were given in the non-operative series. On multivariate regression analysis, the presence of steroid side effects, disease extent, and disease duration were significantly associated with surgery. Patients without side effects had a higher postoperative complication rate than those with minor side effects. We conclude that major side effects are a surgical indication for patients with intractable ulcerative colitis, and that even minor side effects should be taken as a surgical indication in view of the patient's quality of life.

Steroid complications and surgery in intractable ulcerative colitis.

PURPOSE: The accuracy of diagnosis of metastatic lymph nodes for rectal carcinoma has not improved. A low echoic lesion more than 5 mm in size detected by endorectal ultrasonography is preoperatively assessed as a metastatic lymph node. What does a low echoic lesion more than 5 mm in size correspond to histologically? METHODS: Forty-seven patients with lower rectal carcinoma (Term I, 1986–1990) and 48 patients with lower rectal carcinoma (Term II, 1991–1995) undergoing endorectal ultrasonography were reviewed. Surgically resected rectal specimens from 40 patients with rectal carcinoma underwent ultrasonography. Low echoic lesions more than 5 mm in size were taken from resected specimens and were stained with hematoxylin, followed by histologic examination. RESULTS: The accuracy of diagnosis of metastatic lymph nodes of Term II was not higher than that of Term I. Twenty-five low echoic lesions were detected by ultrasonography using 40 resected specimens. Seventeen of these 25 lesions (68 percent) were histologically confirmed to be metastatic lymph nodes. One of 25 (4 percent) was found to be lymphadenitis with no metastasis. Among the 25 lesions, 5 (20 percent) were histologically confirmed to be tumor deposits, 2 (8 percent) fatty tissue, and 22 (88 percent) carcinoma. CONCLUSIONS: Low echoic lesions were histologically confirmed to be tumor deposits (20 percent) and metastatic lymph nodes (68 percent). Although these data show deficiencies and limitations of the accuracy of endorectal ultrasonography, they compare favorably with other series, and no other current technology can show similar accuracy.

Yoshiki Higuchi

Papers

Randomized, controlled trial of lateral node dissection vs. nerve-preserving resection in patients with rectal cancer after preoperative radiotherapy.

Extended lymphadenectomy and preoperative radiotherapy for lower rectal cancers.

Role of p53 and p21/WAF1 detection in patient selection for preoperative radiotherapy in rectal cancer patients.

Steroid complications and surgery in intractable ulcerative colitis.

Limitations of endorectal ultrasonography : What does a Low echoic lesion more than 5 mm in size correspond to histologically?