Mesorectal Excision With or Without Lateral Lymph Node Dissection for Clinical Stage II/III Lower Rectal Cancer (JCOG0212): A Multicenter, Randomized Controlled, Noninferiority Trial.

OBJECTIVE: The aim of the study was to confirm the noninferiority of mesorectal excision (ME) alone to ME with lateral lymph node dissection (LLND) in terms of efficacy. BACKGROUND: Lateral pelvic lymph node metastasis is occasionally found in clinical stage II or III lower rectal cancer, and ME with LLND is the standard procedure in Japan. ME alone, however, is the international standard surgical procedure for rectal cancer. METHODS: Eligibility criteria included histologically proven rectal cancer at clinical stage II/III; main lesion located in the rectum, with the lower margin below the peritoneal reflection; no lateral pelvic lymph node enlargement; Peformance Status of 0 or 1; and age 20 to 75 years. Patients were intraoperatively allocated to undergo ME with LLND or ME alone in a randomized manner. The primary endpoint was relapse-free survival, with a noninferiority margin for the hazard ratio of 1.34. Secondary endpoints included overall survival and local-recurrence-free survival. Analysis was by intention to treat. RESULTS: In total, 701 patients were randomized to the ME with LLND (n = 351) and ME alone (n = 350) groups. The 5-year relapse-free survival in the ME with LLND and ME alone groups were 73.4% and 73.3%, respectively (hazard ratio: 1.07, 90.9% confidence interval 0.84-1.36), with a 1-sided P value for noninferiority of 0.0547. The 5-year overall survival, and 5-year local-recurrence-free survival in the ME with LLND and ME alone groups were 92.6% and 90.2%, and 87.7% and 82.4%, respectively. The numbers of patients with local recurrence were 26 (7.4%) and 44 (12.6%) in the ME with LLND and ME alone groups, respectively (P = 0.024). CONCLUSIONS: The noninferiority of ME alone to ME with LLND was not confirmed in the intent-to-treat analysis. ME with LLND had a lower local recurrence, especially in the lateral pelvis, compared to ME alone.

Prognostic and predictive value of extended RAS mutation and mismatch repair status in stage III colorectal cancer.

The prognostic and predictive value of KRAS gene mutations in stage III colorectal cancer is controversial because many recent clinical trials have not involved a surgery-alone arm. Additionally, data on the significance of extended RAS (KRAS/NRAS) mutations in stage III cancer are not available. Hence, we undertook a combined analysis of two phase III randomized trials, in which the usefulness of adjuvant chemotherapy with tegafur-uracil (UFT) was evaluated, as compared with surgery alone. We determined the association of extended RAS and mismatch repair (MMR) status with the effectiveness of adjuvant chemotherapy. Mutations in KRAS exons 2, 3, and 4 and NRAS exons 2 and 3 were detected by direct DNA sequencing. Tumor MMR status was determined by immunohistochemistry. Total RAS mutations were detected in 134/304 (44%) patients. In patients with RAS mutations, a significant benefit was associated with adjuvant UFT in relapse-free survival (RFS) (hazard ratio = 0.49; P = 0.02) and overall survival (hazard ratio = 0.51; P = 0.03). In contrast, among patients without RAS mutations, there was no difference in RFS or overall survival between the adjuvant UFT group and surgery-alone group. We detected deficient DNA MMR in 23/304 (8%) patients. The MMR status was neither prognostic nor predictive for adjuvant chemotherapy. An interaction analysis showed that there was better RFS among patients treated with UFT with RAS mutations, but not for those without RAS mutations. Extended RAS (KRAS/NRAS) mutations are proposed as predictive indicators with respect to the efficacy of adjuvant UFT chemotherapy in patients with resected stage III colorectal cancer.

Inhibition of intestinal polyp growth by oral ingestion of bovine lactoferrin and immune cells in the large intestine.

Studies using animal models have demonstrated that ingestion of bovine lactoferrin (bLF) inhibits carcinogenesis in the colon and other organs of experimental animals. As a result of these studies, a blinded, randomized, controlled clinical trial was conducted in the National Cancer Center Hospital, Tokyo, Japan to determine whether ingestion of bLF had an effect on the growth of colorectal polyps in humans. Patients with colorectal polyps ≤5 mm diameter and likely to be adenomas ingested 0, 1.5, or 3.0 g bLF daily for 1 year. Ingestion of 3.0 g bLF suppressed the growth of colorectal polyps and increased the level of serum human lactoferrin in trial participants 63 years old or younger. The purpose of the present study was to investigate correlations between immune parameters and changes in polyp size. Trial participants with regressing polyps had increased NK cell activity, increased serum hLF levels (indicating increased neutrophil activity), and increased numbers of CD4+ cells in the polyps. These findings are consistent with a correlation between higher immune activity and suppression of colorectal polyps. In addition, participants with regressing polyps had lower numbers of PMNs and increased numbers of S100A8+ cells in the polyps, consistent with a correlation between lower inflammatory potential in the colon and suppression of colorectal polyps. Trial participants ingesting bLF had increased serum hLF levels, a possible increase in systemic NK cell activity, and increased numbers of CD4+ and CD161+ cells in the polyps. Taken together, our findings suggest that bLF suppressed colorectal polyps by enhancing immune responsiveness.

Case-matched comparison of the short-term outcomes between laparoscopic and open abdominoperineal resection for rectal cancer.

PURPOSE: The aim of this study was to evaluate the short-term surgical outcomes of laparoscopic abdominoperineal resection (APR) for rectal cancer, by comparing it with a case-control series of open APR. METHODS: Fourteen patients with rectal cancer who underwent laparoscopic APR between August 2004 and November 2011 were compared with the open APR group of 14 patients matched for age, gender, and surgical procedure. RESULTS: There were no cases of conversion to laparotomy in the laparoscopic APR group and no mortality in either of the groups. The median operation was longer (P = 0.002), but the median amount of blood loss was smaller (P = 0.019), in the laparoscopic APR group. The median length of hospital stay of the laparoscopic APR group was 8 days, shorter than that of the open APR group (16 days, P < 0.001). The changes of the WBC count and serum CRP level after operations were significantly smaller in the laparoscopic APR group (P < 0.05). There were no significant differences between the groups in terms of the perioperative morbidity and readmission rates within 30 days. CONCLUSION: Patients undergoing laparoscopic APR had superior perioperative outcomes to those undergoing open APR, except for the longer operation.

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.

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<0·0001). Blood loss was significantly higher in the mesorectal excision with lateral lymph node dissection group (576 mL, IQR 352-900) than in the mesorectal excision alone group (337 mL, 170-566; p<0·0001). 26 (7%) patients in the mesorectal excision with lateral lymph node dissection group had lateral pelvic lymph node metastasis. Grade 3-4 postoperative complications occurred in 76 (22%) patients in the mesorectal excision with lateral lymph node dissection group and 56 (16%) patients in the mesorectal excision alone group. The most common grade 3 or 4 postoperative complication was anastomotic leakage (18 [6%] patients in the mesorectal excision with lateral lymph node dissection group 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.

Clinicopathological characteristics and prognostic factors of advanced colorectal mucinous adenocarcinoma.

AIMS: Mucinous adenocarcinoma (MUC) is a histological variant of colorectal adenocarcinoma. The aim of the present study was to characterize clinicopathological features and identify prognostic factors of MUCs. METHODS AND RESULTS: A total of 181 patients with MUC who underwent surgery between 1975 and 2003 were reviewed. The clinicopathological features of these patients were compared with those of 4125 non-MUC patients. Univariate and multivariate analyses were conducted to identify significant prognostic factors in 102 patients with pT3 or pT4 tumour who underwent curative surgery. Patients with MUCs tended to present with more advanced clinical stages. The overall 5-year survival rate of MUC patients was lower than that of non-MUC patients; however, no prognostic difference was found when patients with the same clinical stages were compared. Multivariate analysis revealed male sex, bowel obstruction and infiltrating growth type as independent prognostic factors. Five-year cancer-specific survival rates for MUC patients with ≤1, 2 and 3 risk factors identified by multivariate analysis were 95.5%, 52.1% and 0.0%, respectively (P < 0.001). CONCLUSIONS: Mucinous adenocarcinoma represents a distinct clinicopathological entity. Sex, bowel obstruction and growth patterns might be useful prognostic factors to identify patients with a high risk of recurrence after curative resection of advanced MUCs.

Dome-type carcinoma of the colon; a rare variant of adenocarcinoma resembling a submucosal tumor: a case report.

BACKGROUND: Dome-type carcinoma (DC) is a distinct variant of colorectal adenocarcinoma and less than 10 cases have been described in the literature. Most of the previously reported cases were early lesions and no endoscopic observations have been described so far. We herein report a case of a DC invading the subserosal layer, including endoscopic findings. CASE PRESENTATION: A highly elevated lesion in the transverse colon was diagnosed by colonoscopy in a 77-year-old man. The tumor appeared to be similar to a submucosal tumor (SMT), however, a demarcated area of reddish and irregular mucosa was observed at the top of the tumor. There were no erosions or ulcers. Laparoscopic-assisted right hemicolectomy was performed and pathological examination revealed a well-circumscribed tumor invading the subserosal layer. The tumor was a well-differentiated adenocarcinoma associated with a dense lymphocytic infiltration and showed expansive growth. The overlying mucosal layer showed high-grade dysplasia. CONCLUSION: The present lesion was diagnosed as a DC of the colon invading the subserosal layer. Because the association of mucosal dysplasia is common in DCs, the detection of dysplastic epithelium would be important to discriminate DCs from SMTs.

Prognostic factors of rectal cancer patients with lateral pelvic lymph node metastasis.

BACKGROUND/AIMS: We examined the clinicopathological characteristics of rectal cancer patients with lateral pelvic lymph node (LPLN) metastasis in order to clarify their associated prognostic factors. METHODOLOGY: A total of 91 rectal cancer patients with LPLN metastasis who underwent curative resection at the National Cancer Center Hospital between 1985 and 2004 were reviewed. RESULTS: The five-year overall survival rate and disease-free survival rate of the studied patient were 39% and 27%, respectively. Univariate analysis showed that tumor differentiation, lymphatic invasion, venous invasion, mesenteric lymph node status and LPLN status were significant prognostic factors. Multivariate analysis showed that tumor differentiation, mesenteric lymph node status and LPLN status were significant prognostic factors. Among 15 patients with LPLN metastasis and without mesenteric lymph node metastasis, 11 patients (73.3%) with one or two LPLN metastases survived more than five years. Among 12 patients with four or more LPLN metastases, two(16.7%) survived more than five years. CONCLUSIONS: Tumor differentiation, mesenteric lymph node status and LPLN status are significant prognostic factors of patients with LPLN metastasis. Because some patients with LPLN metastasis survive for a long period, LPLN dissection should be considered for them.

Validation of the histone methyltransferase EZH2 as a therapeutic target for various types of human cancer and as a prognostic marker.

The emphasis in anticancer drug discovery has always been on finding a drug with great antitumor potential but few side-effects. This can be achieved if the drug is specific for a molecular site found only in tumor cells. Here, we find the enhancer of zeste homolog 2 (EZH2) to be highly overexpressed in lung and other cancers, and show that EZH2 is integral to proliferation in cancer cells. Quantitative real-time PCR analysis revealed higher expression of EZH2 in clinical bladder cancer tissues than in corresponding non-neoplastic tissues (P < 0.0001), and we confirmed that a wide range of cancers also overexpress EZH2, using cDNA microarray analysis. Immunohistochemical analysis showed positive staining for EZH2 in 14 of 29 cases of bladder cancer, 135 of 292 cases of non-small-cell lung cancer (NSCLC), and 214 of 245 cases of colorectal cancer, whereas no significant staining was observed in various normal tissues. We found elevated expression of EZH2 to be associated with poor prognosis for patients with NSCLC (P = 0.0239). In lung and bladder cancer cells overexpressing EZH2, suppression of EZH2 using specific siRNAs inhibited incorporation of BrdU and resulted in significant suppression of cell growth, even though no significant effect was observed in the normal cell strain CCD-18Co, which has undetectable EZH2. Because EZH2 expression was scarcely detectable in all normal tissues we examined, EZH2 shows promise as a tumor-specific therapeutic target. Furthermore, as elevated levels of EZH2 are associated with poor prognosis of patients with NSCLC, its overexpression in resected specimens could prove a useful molecular marker, indicating the necessity for a more extensive follow-up in some lung cancer patients after surgical treatment.

Short-term outcomes of laparoscopic intersphincteric resection for lower rectal cancer and comparison with open approach.

BACKGROUND/AIMS: To evaluate the short-term surgical outcomes of laparoscopic intersphincteric resection (ISR) for lower rectal cancer, and to compare them with a case-control series of open ISR. METHODS: Between July 2002 and March 2011, 29 patients with lower rectal cancer underwent laparoscopic ISR, and 22 of 29 patients who underwent laparoscopic ISR were compared with the control open ISR group of patients matched for age, gender, operative procedure and pathological stage. RESULTS: There was no perioperative mortality, 8 complications occurred in 7 patients, and the morbidity rate was 24.1% (7/29). Leakage occurred in 1 patient (3.4%) in the laparoscopic ISR group. Regarding the matched case-control study, the operative time was significantly longer (p = 0.0007), but blood loss was significantly lower (p = 0.0003) in the laparoscopic ISR group. The median postoperative hospital stay was 8 days in the laparoscopic ISR group, which was significantly shorter than in the open ISR group (14 days). Postoperative complication rates were similar. In the laparoscopic ISR group, the levels of C-reactive protein on postoperative days 1-3 were significantly lower than in the open ISR group. CONCLUSIONS: Laparoscopic ISR for lower rectal cancer provides benefits in the early postoperative period without increasing morbidity or mortality.

[Treatment of lateral node metastasis from lower rectal cancer].

Lateral lymphatics of the rectum originate in the area where branches of the inferior hypogastric plexus and the middle rectal vessels from the internal iliac vessels enter the mesorectum below the level of the peritoneal reflection in the pelvis, then reach the bifurcation of iliac vessels along the internal iliac vessels. Among lateral lymph nodes, the middle rectal, obturator, and internal iliac lymph nodes are important from the viewpoint of both the incidence of metastais and treatment effects. Although total mesorectal excision (TME) had become the standard surgical treatment for rectal cancer by the 1990s, this technique does not treat lateral node metastasis. A randomized clinical trial of TME versus D3 lymphadenectomy (JCOG0212) was started in 2003, and the registration of 701 patients with lower rectal cancer was completed in August 2010. The results of this clinical trial are highly anticipated. In Japan, where the rate of local recurrence after surgery is low, patients at high risk of local recurrence such as those with lateral node metastasis, T4 disease, and multiple lymph node metastases in the mesorectum should be selected to receive preoperative chemoradiation. Japanese surgeons who treat rectal cancers are in an advantageous position because they have the additional measure of lateral node dissection along with TME and chemoradiotherapy.

Risk factors for surgical site infection and association of surgical site infection with survival of lower rectal cancer patients without clinical lateral pelvic lymph node metastasis (clinical Stage II/III): Analysis of data from JCOG0212.

This study aimed to examine the risk factors for surgical site infection (SSI) and the association of that with recurrence in JCOG0212. The results for secondary endpoints showed that compared with the mesorectal excision (ME) alone group, ME with lateral lymph node dissection (LLND) group showed significantly longer operative time and significantly higher blood loss. These results suggested that LLND was a risk factor for SSI. All 701 patients registered in JCOG0212 were analyzed in this study. Wound infection was defined as incisional/deep SSI, and pelvic abscess and anastomotic leakage were defined as organ/space SSI. The risk factors for the incidence of SSI and the effect of SSI on relapse-free survival (RFS) were investigated. Multivariable odds ratio of Grade 2 or higher all SSI was 0.58 [95% Confidence interval: 0.36-0.93] for female (vs. male) and that of Grade 2 or higher incisional/deep SSI was 2.24 [1.03-4.86] for blood infusion. For RFS, patients with Grade 3 or higher all SSI showed poor prognosis (multivariable hazard ratio: 1.66 [1.03-2.68]). LLND is not significant factor for the incidence of all SSI. Male sex might be a risk factor of Grade 2 or higher SSI, and blood transfusion is a possible risk factor of Grade 2 or higher incisional/deep SSI. Grade 3 or higher all SSI might be a significant worse prognostic factor for lower rectal cancer.

Plasma concentrations of VCAM-1 and PAI-1: a predictive biomarker for post-operative recurrence in colorectal cancer.

This prospective study used antibody suspension bead arrays to identify biomarkers capable of predicting post-operative recurrence with distal metastasis in patients with colorectal cancer. One hundred colorectal cancer patients who underwent surgery were enrolled in this study. The median follow-up period was 3.9 years. The pre-operative plasma concentrations of 24 angiogenesis-related molecules were analyzed with regard to the TNM stage and the development of post-operative recurrence. The concentrations of half of the examined molecules (13/24) increased significantly according to the TNM stage (P < 0.05). Meanwhile, a multivariate logistic regression analysis revealed that the concentrations of vascular cell adhesion molecule 1 (VCAM-1) and plasminogen activator inhibitor-1 (PAI-1) were significantly higher in the post-operative recurrence group. The VCAM-1 and PAI-1 model discriminated post-operative recurrence with an area under the curve of 0.82, a sensitivity of 0.75, and a specificity of 0.73. A leave-one-out cross-validation was applied to the model to assess the prediction performance, and the result indicated that the cross-validated error rate was 12.5% (12/96). In conclusion, our results demonstrate that antibody suspension bead arrays are a powerful tool to screen biomarkers in the clinical setting, and the plasma levels of VCAM-1 and PAI-1 together may be a promising biomarker for predicting post-operative recurrence in patients with colorectal cancer.

Is surgical resection justified for stage IV colorectal cancer patients having bilobar hepatic metastases?--an analysis of survival of 77 patients undergoing hepatectomy.

BACKGROUND: Surgical indication for stage IV colorectal cancer patients with bilobar hepatic metastases may be controversial. METHODS: Retrospective cohort analysis was performed using data of 200 patients who underwent surgical resections for synchronous metastases of colorectal cancer between 1990 and 2005. Of these, 80 patients had solitary, 43 had unilobar multiple, and 77 had bilobar metastases. Prognostic factors of the 77 bilobar metastases were evaluated using multivariate analysis. The survival was compared with that of 95 patients undergoing chemotherapy for unresectable bilobar hepatic metastases. RESULTS: Univariate and multivariate analyses revealed that the number of metastasis (≥6) [relative risk (RR), 2.7; P = 0.002] and depth of invasion (T4) (RR, 2.0; P = 0.04) were predictors of survival of the 77 patients. The survival of 11 T4 cancer patients with six or more metastases was poor, but significantly better than that of 95 patients with unresectable bilobar metastases (P = 0.04). CONCLUSION: Surgical resection in stage IV colorectal cancer patients having bilobar hepatic metastases was justified in the present setting.

Cancer prevention by bovine lactoferrin: from animal studies to human trial.

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers and, despite improved colonoscopic screening, CRC is a leading cause of death from cancer. Administration of bovine lactoferrin (bLF) suppresses carcinogenesis in the colon and other organs of test animals, and recently it was shown that ingestion of bLF inhibits the growth of adenomatous polyps in human patients. Here we review work which established bLF as an anti-carcinogenic agent in laboratory animals and the results of a clinical trial which demonstrated that bLF can reduce the risk of colon carcinogenesis in humans.

A case of advanced rectal adenocarcinoid tumor with long-term survival.

Adenocarcinoid tumor most commonly occurs in the appendix and a tumor arising in the rectum is extremely rare. A 58-year-old man underwent total pelvic exenteration with extended lateral lymph node dissection for rectal adenocarcinoid tumor invading the urethra with lateral lymph node metastasis. Microscopically and immunohistochemically, the tumor consisted of carcinoid-like components and signet-ring-cell-carcinoma-like components, and an adenocarcinoid tumor was diagnosed. Postoperatively, the patient received combination chemotherapy of fluorouracil and leucovorin as an adjuvant therapy. Three years and 5 years after the initial surgery, the patient developed left groin and left external iliac lymph node recurrences, and lymphadenectomy was performed each time. As a result, the patient is alive more than 5 years after the initial surgery. There is no consensus on the indication of surgical treatment for adenocarcinoid tumor. However, in advanced cases, an aggressive surgical procedure might result in long-term survival when resectable.

Improving prediction of lateral node spread in low rectal cancers--multivariate analysis of clinicopathological factors in 1,046 cases.

INTRODUCTION: This study aims to search for independent predictors of lateral node metastasis in low rectal cancers. MATERIALS AND METHODS: We analyzed 1,046 patients who underwent curative resection for lower rectal cancer in our prospectively collected database. All lymph nodes were dissected from the fresh specimen, and their locations were documented prospectively according to the classification by the Japanese Society of Cancer of the Colon and Rectum. RESULTS: More than 35% of the patients had demonstrated upward nodal metastasis in the direction of the inferior mesenteric vessels, while 11% demonstrated lateral node metastasis, which was present in 17.3% of patients with T3 and T4 lesions. Multivariate analysis revealed five factors to be statistically significant independent predictors of lateral node metastasis: female sex, tumors that were not well differentiated, pathological T3 and above, positive microscopic lymphatic invasion, and positive mesorectal nodes. Using the variables sex, differentiation, T stage, and mesorectal nodes as risk factors, because these could be elucidated preoperatively, the presence of lateral node metastasis was then analyzed according to the number of positive risk factors. When there were fewer than three positive factors, the risk of lateral nodal spread was low (4.5%). When three or more risk factors were positive, the odds of lateral node metastasis were more than 7.5 times higher (p < 0.001). CONCLUSION: The findings of this study provide a scoring system that can be used to guide the clinician to the presence of lateral node metastasis in low rectal cancers.

A novel multimodal approach for locally advanced rectal cancer involving the pelvic sidewall.

BACKGROUND/AIMS: Total mesorectal excision (TME) is the standard surgery for locally advanced rectal cancer. In instances when the primary tumor invades adjacent organs, en-bloc excision is required for a curative resection. However, when lateral pelvic lymph node metastases involve the pelvic sidewall, treatment strategy is not established yet. METHODS: We here report on a case treated with a novel multimodal approach consisting of neoadjuvant chemoradiotherapy, followed by TME plus extended lateral pelvic lymph node dissection and en-bloc resection of the internal iliac artery and vein. RESULTS: There were no complications. Serial sections of the rectum showed only fibrosis and inflammatory cell aggregation. None of the mesorectal nodes contained tumor cells, but one each of the right and left lateral pelvic nodes demonstrated residual adenocarcinoma with foci of necrosis and fibrosis. Chemoradiotherapy increased the circumferential resection margin from 0 mm to 2 mm. An additional 5 mm clearance was obtained following resection of the internal iliac vessels yielding a total clearance margin of 7 mm. The patient remained free of disease 2.5 years after surgery. CONCLUSION: This seems to be the only strategy offering the possibility of cure for such a condition.

Male urinary and sexual functions after mesorectal excision alone or in combination with extended lateral pelvic lymph node dissection for rectal cancer.

BACKGROUND: Mesorectal excision reduced the incidence of genitourinary dysfunction compared with conventional surgery. In Japan, extended lateral pelvic lymph node dissection (ELD) is added to mesorectal excision when lateral pelvic node metastasis is suspected. The aim of this study was to evaluate male genitourinary function after mesorectal excision or mesorectal excision plus ELD for rectal cancer. METHODS: According to the degree of pelvic-plexus preservation (PPP) and ELD, patients were grouped into PG1, mesorectal excision alone (bilateral PPP without ELD) (n = 27); PG2, bilateral PPP with ELD (n = 12); PG3, unilateral PPP with ELD (n = 26); and PG4, no PPP with ELD (n = 4). The assessment included measurements of the time interval to residual urine becoming <50 mL, interviews assessing sexual function, and nocturnal penile tumescence measurements. RESULTS: Proportions of patients with residual urine becoming <50 mL within 14 days after surgery were 96% in PG1, 73% in PG2, 23% in PG3, and 0% in PG4 (P < .001). Proportions of patients answering the ability to maintain sexual intercourse at 1 year were 95% in PG1, 56% in PG2, 45% in PG3, and 0% in PG4 (P < .001). Proportions of patients having nocturnal penile rigidity of >65% at 1 year were 95% in PG1, 33% in PG2, 50% in PG3, and 0% in PG4 (P < .001). CONCLUSIONS: Patients undergoing mesorectal excision alone can expect excellent genitourinary function, but functional results after mesorectal excision plus ELD are far worse. Degrees of dysfunction depend on the extents of both autonomic nerve resection and ELD.

Accuracy of high-resolution magnetic resonance imaging in preoperative staging of rectal cancer.

BACKGROUND: To achieve better prognosis and quality of life for patients with rectal cancer, extent of surgery and neoadjuvant chemoradiotherapy should accurately reflect disease extent. The aim of this study was to evaluate accuracy of high-resolution magnetic resonance imaging (HRMRI) for preoperative staging of rectal cancer. METHODS: Between 2001 and 2003, 104 patients with primary rectal cancer were examined with HRMRI and underwent radical surgery. Transmural invasion depth and lymph node metastasis were assessed prospectively and classified according to the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) system by both HRMRI and histopathology, and results were compared. Criteria for mesorectal and lateral pelvic lymph node involvement were short-axis diameters of > or =5 mm and > or =4 mm, respectively. RESULTS: There were 15 pT1, 25 pT2, 50 pT3, and 14 pT4 tumors. Overall accuracy rate for transmural invasion depth was 84%. The mesorectal fascia could be visualized in 98% of patients. Twenty-three patients had mesorectal fascia involvement and the overall accuracy rate was 96% (sensitivity, 96%; specificity, 96%). Fifty-three patients had mesorectal lymph node metastasis and the overall accuracy rate was 74% (sensitivity, 83%; specificity, 64%). Lateral pelvic lymph node metastasis was observed in 15 patients and the overall accuracy rate was 87% (sensitivity, 87%; specificity, 87%). CONCLUSIONS: HRMRI was moderately accurate for prediction of mesorectal lymph node metastasis and highly accurate regarding transmural invasion depth, and mesorectal fascia and lateral pelvic node involvement. Therefore, HRMRI appears useful for preoperative decision-making in rectal cancer treatment.