Laparoscopic and endoscopic cooperative surgery (LECS) to overcome the limitations of endoscopic resection for colorectal tumors.

Background and study aims We developed a laparoscopy endoscopy cooperative surgery (LECS) to overcome the limitations of endoscopic resection for colorectal tumors. The aim of this study was to evaluate the feasibility of LECS, which combines endoscopic submucosal dissection (ESD) and laparoscopic partial colectomy. Patients and methods We performed LECS for 17 colorectal tumors in 17 patients (male:female 10:7; mean age, 66.5 years). The clinicopathological outcomes of these 17 cases and the feasibility of LECS were evaluated retrospectively. Indications for LECS were as follows: 1) intramucosal cancer and adenoma accompanied by wide and severe fibrosis; 2) intramucosal cancer and adenoma involving the diverticulum or appendix; and 3) submucosal tumors. Results We successfully performed LECS procedures in 17 cases (intramucosal cancer [n = 6], adenoma [n = 9], schwannoma [n = 1], and gastro-intestinal stromal tumour [GIST] [n = 1]. Mean tumor diameter was 22.4 mm (range, 8 - 41 mm). LECS was successfully performed in all 17 cases without conversion to open surgery; the R0 rate was 100 %. LECS was applied to the following situations: involving the appendix (n = 6), tumor accompanied by severe fibrosis (n = 5), involving the diverticulum (n = 3), submucosal tumor (n = 2), and poor endoscopic operability (n = 1). We experienced no adverse events (e. g., leakage or anastomotic stricture) and the median hospital stay was 6.4 dayus (range, 4 to 12). All 17 patients who were followed for ≥ 3 months (median, 30.8 months; range, 3 - 72 months) showed no residual/local recurrence. Conclusion LECS was a safe, feasible, minimally invasive procedure that achieved full-thickness resection of colorectal tumors and showed excellent clinical outcomes.

Recurrence 30 Years after Surgical Resection of a Localized Rectal Neuroendocrine Tumor.

Localized small rectal neuroendocrine tumors (NETs) without any vascular involvement rarely metastasize, and their resection alone is considered curative. We herein report a case of localized rectal NET (10×8 mm) without vascular involvement. Although resected initially, it recurred as liver metastasis 30 years later. For rectal NETs smaller than 10 to 20 mm, surveillance for 12 months is considered sufficient. However, this case suggests that such tumors can recur even 30 years after curative resection. The interval of recurrence is the longest among reported cases.

Selective lateral pelvic lymph node dissection in patients with advanced low rectal cancer treated with preoperative chemoradiotherapy based on pretreatment imaging.

BACKGROUND: The significance of lateral pelvic lymph node (LPLN) metastasis in advanced low rectal cancer treated with preoperative chemoradiotherapy (CRT) remains unclear. The objective of this study was to evaluate the outcomes of selective LPLN dissection (LPLD) based on the pretreatment imaging in patients with advanced low rectal cancer treated with preoperative CRT. METHODS: We reviewed 127 consecutive patients with clinical stage II-III low rectal cancer below the peritoneal reflection who underwent preoperative CRT and curative resection. LPLD was performed in patients with suspected LPLN metastasis based on MDCT or MRI before CRT (LPLD group, N = 38), and only total mesorectal excision (TME) was performed in patients without suspected LPLN metastasis (TME group, N = 89). Clinical characteristics and the oncological outcome were compared between groups. RESULTS: The median tumor-to-anal verge distance was 40 mm in both groups. The median maximum long-axis LPLN diameter before CRT was 0 mm in the TME group and 10.5 mm in the LPLD group. Pathological LPLN metastasis was confirmed in 25 patients (66 %) in the LPLD group. Local recurrence at LPLN developed in 3 patients (3.4 %) in the TME group and in none (0 %) of the LPLD group. Multivariate analysis showed that only ypN was an independent prognostic factor for relapse-free survival (RFS), but LPLN metastasis was not associated with poor RFS. CONCLUSIONS: The incidence of LPLN metastasis is high even after preoperative CRT, and LPLD might improve local control and survival of patients with LPLN metastasis in advanced low rectal cancer treated with preoperative CRT.

Treatment strategy for rectal carcinoids: a clinicopathological analysis of 229 cases at a single cancer institution.

BACKGROUND AND AIM: A treatment strategy for tumors with only venous invasion and characteristics of small rectal carcinoids with metastasis have not been clearly documented. The present study aims to determine the risk factors for lymph node metastasis and to elucidate characteristics of small tumors with metastasis. METHODS: We investigated a total of 229 patients with rectal carcinoids. The relationship between each clinicopathological variable and the presence of lymph node metastasis was evaluated. RESULTS: Tumor size (larger than 10 mm), presence of central depression, depth of tumor invasion, lymphatic invasion, and venous invasion were significantly associated with the incidence of lymph node metastasis (P < 0.001). Multivariate analysis revealed that tumor size (odds ratio: 63.3, P < 0.001) and venous invasion (odds ratio: 40.9, P < 0.001) were independently predictive of lymph node metastasis. In 204 patients with small (no larger than 10 mm) tumors, 10 patients had lymph node metastasis. All 10 tumors had low proliferation values indicated by mitosis and Ki-67 index. Multivariate analysis for the 204 patients revealed that only venous invasion was independently associated with metastasis (odds ratio: 40.1, P < 0.001). Five-year disease free survival rates of the total patients with metastasis and without metastasis were 81.1% and 95.5%, respectively (P < 0.001, log-rank test). CONCLUSIONS: Venous invasion as well as tumor size and lymphatic invasion indicates high malignant potential to metastasize to lymph node and would provide useful information in considering the addition of radical surgery. Postoperative pathological examinations of specimens obtained by local resection are very important to avoid underestimation.

Chromosomal instability (CIN) phenotype, CIN high or CIN low, predicts survival for colorectal cancer.

PURPOSE: To examine whether chromosomal instability (CIN) phenotype, determined by the severity of CIN, can predict survival for stages II and III colorectal cancer (CRC). PATIENTS AND METHODS: We determined microsatellite instability (MSI) and loss of heterozygosity (LOH) status in 1,103 patients (training [n = 845] and validation [n = 258] sets with stages II and III CRC). The LOH ratio was defined as the frequency of LOH in chromosomes 2p, 5q, 17p, and 18q. According to the LOH ratio, non-MSI high tumors were classified as CIN high (LOH ratio ≥ 33%) or CIN low (LOH ratio < 33%). CIN-high tumors were subclassified as CIN high (mild type; LOH ratio < 75%) or CIN high (severe type; LOH ratio ≥ 75%). We used microarrays to identify a gene signature that could classify the CIN phenotype and evaluated its ability to predict prognosis. RESULTS: CIN high showed the worst survival (P < .001), whereas there was no significant difference between CIN low and MSI high. CIN high (severe type) showed poorer survival than CIN high (mild type; P < .001). Multivariate analysis revealed that CIN phenotype was an independent risk factor for disease-free and overall survival, respectively, in both the training (P < .001 and P = .0155) and validation sets (P < .001 and P = .0076). Microarray analysis also revealed that survival was significantly poorer in those with the CIN-high than in the CIN-low gene signature (P = .0203). In a validation of 290 independent CRCs (GSE14333), the CIN-high gene signature showed significantly poorer survival than the CIN-low signature (P = .0047). CONCLUSION: The CIN phenotype is a predictive marker for survival and may be used to select high-risk patients with stages II and III CRC.

Results of a Japanese nationwide multi-institutional study on lateral pelvic lymph node metastasis in low rectal cancer: is it regional or distant disease?

OBJECTIVE: To evaluate whether lateral pelvic lymph nodes (LNs) in low rectal cancer are metastatic disease or part of regional LNs that are amenable to curative resection. BACKGROUND: It is highly controversial whether lateral pelvic LNs should be considered as regional or distant disease, although the American Joint Committee on Cancer (AJCC) defines internal iliac LNs as regional LNs of rectal cancer. METHODS: Data of patients with stage I to III low rectal cancer who underwent curative resection from 1978 to 1998 were extracted from the multi-institutional registry of large bowel cancer in Japan. Patients with only mesorectal LN metastasis were classified as the mesorectal-LN group. Patients with lateral pelvic LN metastasis localized to or extending beyond the internal iliac area were classified as the internal lateral pelvic lymph nodes (LPLN) group and external-LPLN group, respectively. Overall survival (OS) and cancer-specific survival (CSS) were compared between the groups. RESULTS: Lateral pelvic LN dissection was performed in 5789 (50%) of 11,567 patients. Overall, 3905 (34%), 411 (3.6%), and 244 (2.1%) patients were classified as the mesorectal-LN, internal-LPLN, and external-LPLN groups, respectively. When the mesorectal LN group was subdivided as defined by the AJCC, both 5-year OS and CSS were not significantly different between the N2a and internal-LPLN groups (OS: 45% vs 45%, P = 0.9585; CSS: 51% vs 49%, P = 0.5742), and the N2b and external-LPLN groups (OS: 32% vs 29%, P = 0.3342; CSS: 37% vs 34%, P = 0.4347). OS and CSS were significantly better in the external-LPLN group than in stage IV patients who underwent curative resection (OS: 29% vs 24%, P = 0.0240; CSS: 34% vs 27%, P = 0.0117). CONCLUSIONS: Lateral pelvic LNs can be considered as regional LNs in low rectal cancer, although metastasis extending beyond the internal iliac area is associated with poorer survival.

Nationwide survey on adult type chronic intestinal pseudo-obstruction in surgical institutions in Japan.

BACKGROUND: No appropriate management of chronic intestinal pseudo-obstruction (CIP) has been established. PATIENTS AND METHODS: The clinicopathological parameters of 103 cases collected by a nationwide questionnaire study were reviewed. RESULTS: The CIP cases were primary in 86 (83%) cases and secondary in 15 (15%) cases. The age of onset of the primary type was significantly younger than that of the secondary type (p = 0.011). The diseased segments of the bowel were the large bowel in 60 (58%), the small bowel in 17 (17%), and both in 23 (22%) cases, respectively. Abdominal distension and pain were common symptoms regardless of the types of the diseased bowel; however, constipation was frequently seen in the large bowel type (p = 0.0258). Vomiting and diarrhea were seen with marginally higher frequency in the small bowel type (p = 0.0569, 0.0642). Surgical treatment was most effective in the large bowel type, less effective in the small bowel type, and least effective in the large and small bowel type. The prognosis of the primary CIP was significantly better than that of the secondary CIP (p = 0.033). CONCLUSIONS: The segments of the diseased bowels should be considered in determining the indications for surgical treatments in CIP patients.

Number of lymph nodes retrieved is an important determinant of survival of patients with stage II and stage III colorectal cancer.

OBJECTIVE: The number of lymph nodes retrieved is recognized to be a prognostic factor of Stage II colorectal cancer. However, the prognostic significance of the number of lymph nodes retrieved in Stage III colorectal cancer remains controversial. METHODS: The relationship between the number of lymph nodes retrieved and clinical and pathological factors, and significance of the number of lymph nodes retrieved for prognosis of Stage II and III colorectal cancer were investigated. A total of 16 865 patients with T3/T4 colorectal cancer who had R0 resection were analysed. RESULTS: The arithmetic mean of the number of lymph nodes retrieved of all cases was 20.0. The number of lymph nodes retrieved were varied according to several clinical and pathological variables with significant difference, and the greater difference was observed in scope of nodal dissection. Survival of Stages II and III was significantly associated with the number of lymph nodes retrieved. Five-year overall survival of the patients with ≤ 9 of the number of lymph nodes retrieved and those with >27 differed by 6.4% for Stage II colon cancer, 8.8% for Stage III colon cancer, 12.5% for Stage II rectal cancer and 10.6% for Stage III rectal cancer. With one increase in the number of lymph nodes retrieved, the mortality risk was decreased by 2.1% for Stage II and by 0.8% for Stage III, respectively. The cut-off point of the number of lymph nodes retrieved was not obtained. CONCLUSIONS: The number of lymph nodes retrieved was shown to be an important prognostic variable not only in Stage II but also in Stage III colorectal cancer, and it was most prominently determined by the scope of nodal dissection. A cut-off value for the number of lymph nodes retrieved was not found, and it is necessary to carry out appropriate nodal dissection and examine as many lymph nodes as possible.

Is rectal cancer prone to metastasize to lymph nodes than colon cancer?

The biology of colorectal cancer differs according to its location within the large intestine. A report published in a previous issue of World Journal of Gastroenterology (November 2010) evaluated the importance of tumor location as a risk factor for lymph node metastasis in colorectal cancer, and showed that rectal cancer is prone to metastasize to lymph nodes as compared with colon cancer. However, in order to conclude that the tumor location is independently associated with the occurrence of lymph node metastasis, it is necessary to consider a selection bias or other patient- and tumor-related factors carefully.

Predicting ulcerative colitis-associated colorectal cancer using reverse-transcription polymerase chain reaction analysis.

BACKGROUND: Widespread genetic alterations are present not only in ulcerative colitis (UC)-associated neoplastic lesions but also in the adjacent normal colonic mucosa. This suggests that genetic changes in nonneoplastic mucosa might be effective markers for predicting the development of UC-associated cancer (UC-Ca). This study aimed to build a predictive model for the development of UC-Ca based on gene expression levels measured by reverse-transcription polymerase chain reaction (RT-PCR) analysis in nonneoplastic rectal mucosa. PATIENTS AND METHODS: Fifty-three UC patients were examined, of which 10 had UC-Ca and 43 did not (UC-NonCa). In addition to the 40 genes and transcripts previously shown to be predictive for developing UC-Ca in our microarray studies, 149 new genes, reported to be important in carcinogenesis, were selected for low density array (LDA) analysis. The expression of a total of 189 genes was examined by RT-PCR in nonneoplastic rectal mucosa. RESULTS: We identified 20 genes showing differential expression in UC-Ca and UC-NonCa patients, including cancer-related genes such as CYP27B1, RUNX3, SAMSN1, EDIL3, NOL3, CXCL9, ITGB2, and LYN. Using these 20 genes, we were able to build a predictive model that distinguished patients with and without UC-Ca with a high accuracy rate of 83% and a negative predictive value of 100%. CONCLUSION: This predictive model suggests that it is possible to identify UC patients at a high risk of developing cancer. These results have important implications for improving the efficacy of surveillance by colonoscopy and suggest directions for future research into the molecular mechanisms of UC-associated cancer.

Factors affecting encouragement of relatives among families with Lynch syndrome to seek medical assessment.

Lynch syndrome (HNPCC) is an autosomal dominant hereditary cancer syndrome, and members of affected families are at-risk for developing colorectal and other associated tumors. Such individuals should disseminate familial genetic information, so they can seek specific medical assessment or genetic testing to reduce mortality and morbidity rates by early detection. Since published results have been encouraging, we explored which factors influence the likelihood of good communication within families regarding medical assessment. We studied 40 individuals from 33 families who satisfied the Japanese clinical criteria for Lynch syndrome and their relatives at our hospital. We determined the status of relatives of the 40 individuals after genetic counseling and testing using questionnaires and semi-structured interviews based on pedigree charts. We also examined their knowledge or perception of colorectal cancer syndrome, levels of intimacy and whether or not they encouraged their relatives to have specific medical assessments. We found that 75% of the individuals advised their relatives to seek medical assessment, and any significant background factors that promoted such encouragement were observed. They tended to encourage first degree relatives and discuss the issue with other family members such as spouses before undertaking such attempts at encouragement. The reasons and methods of imparting encouragement were essentially identical. We also found that genetic testing for at-risk or more distant relatives was not encouraged so often. Therefore, providing individuals who have been tested for Lynch syndrome with opportunities for disseminating familial genetic information through appropriate genetic counseling is important.

Gene expression signature and response to the use of leucovorin, fluorouracil and oxaliplatin in colorectal cancer patients.

PURPOSE: FOLFOX (a combination of leucovorin, fluorouracil and oxaliplatin) has achieved substantial success in the treatment of colorectal cancer (CRC) patients. However, about half of all patients show resistance to this regimen and some develop adverse symptoms such as neurotoxicity. In order to select patients who would benefit most from this therapy, we aimed to build a predictor for the response to FOLFOX using microarray gene expression profiles of primary CRC samples. PATIENTS AND METHODS: Forty patients who underwent surgery for primary lesions were examined. All patients had metastatic or recurrent CRC and received modified FOLFOX6. Responders and nonresponders were determined according to the best observed response at the end of the first-line treatment. Gene-expression profiles of primary CRC were determined using Human Genome GeneChip arrays U133. We identified discriminating genes whose expression differed significantly between responders and nonresponders and then carried out supervised class prediction using the k-nearest-neighbour method. RESULTS: We identified 27 probes that were differentially expressed between responders and nonresponders at significant levels. Based on the expression of these genes, we constructed a FOLFOX response predictor with an overall accuracy of 92.5%. The sensitivity, specificity, positive and negative predictive values were 78.6%, 100%, 100% and 89.7%, respectively. CONCLUSION: The present model suggests the possibility of selecting patients who would benefit from FOLFOX therapy both in the metastatic and the adjuvant setting. To our knowledge, this is the first study to establish a prediction model for the response to FOLFOX chemotherapy based on gene expression by microarray analysis.

Mid-term prognosis after endoscopic resection for submucosal colorectal carcinoma: summary of a multicenter questionnaire survey conducted by the colorectal endoscopic resection standardization implementation working group in Japanese Society for Cancer of the Colon and Rectum.

We carried out a retrospective questionnaire survey of 792 submucosal colorectal carcinoma (CRC) cases from 15 institutions affiliated with the Colorectal Endoscopic Resection Standardization Implementation Working Group in Japanese Society for Cancer of the Colon and Rectum. In these cases, endoscopic resection (ER) and surveillance was carried out without additional surgical resection. Local recurrence or metastasis was observed in 18 cases. Local submucosal recurrence was observed in 11 cases, and metastatic recurrence was observed in 13 cases. Among the 15 cases in which the depth of submucosal invasion was measured, two cases showed depth less than 1000 µm, which has other risk factors for metastasis. Metastatic recurrence was observed in the lung, liver, lymph node, bone, adrenal glands, and the brain; in some cases, metastatic recurrence was observed in multiple organs. Death due to primary disease was observed in six cases. The average interval between ER and recurrence was 19.7 ± 9.2 months. In 16 cases, recurrence was observed within 3 years after ER. Thus, validity of ER without additional surgical resection for cases with the conditions that the depth of submucosal invasion is less than 1000 µm and the histological grade is well or moderately differentiated adenocarcinoma with no lymphatic and venous involvement was proven.

Multimedia article. Lateral lymph node dissection with preoperative chemoradiation for locally advanced lower rectal cancer through a laparoscopic approach.

BACKGROUND: Lateral lymph node (LLN) dissection contributes to a decrease in local recurrence and prolongs survival in locally advanced lower rectal cancer patients as compared with total mesorectal excision (TME) alone [1, 2]. However, this procedure is also accompanied by increased bleeding and postoperative complications [3, 4]. Recently, laparoscopic TME has become a safe and feasible approach for lower rectal cancer even after preoperative chemoradiation [5-7]. Laparoscopic LLN dissection could be the next promising approach and could not only provide a survival benefit but also minimize bleeding and postoperative complications with enhanced visualization, as reported in gynecological and urological malignancies [8, 9]. METHODS: A total of 14 patients underwent laparoscopic LLN dissection with TME after preoperative chemoradiation. Our standardized procedure for LLN dissection is seen in the video. After completion of TME, as described previously [5, 6], the obturator nerve is identified between the external and internal iliac arteries and the obturator lymph nodes are dissected along this nerve to reach the obturator foramen. The internal iliac lymph nodes are dissected along the surface of the internal iliac vein, carefully preserving the pelvic nerve plexus. RESULTS: The procedure was successfully accomplished in all cases without conversion to laparotomy. The median amount of bleeding and operative time were 25 (range=5-1190) ml and 413 (range=277-596) min, respectively. The median number of retrieved lymph nodes was 23 (range=14-33), and eight cases had metastasis in the retrieved LLNs. Postoperative recovery was excellent, with median time to flatus of 1 (range=1-2) day. Postoperative complications included three wound infections, one anastomotic leakage, and one presacral abscess, and all recovered without surgical intervention. There was no urinary dysfunction. After a mean follow-up of 17 (range=8-43) months, all 14 patients were alive without recurrence. CONCLUSIONS: Laparoscopic LLN dissection can be safely conducted with minimal postoperative complications.

Ulcerative colitis-associated colorectal cancer shows a poorer survival than sporadic colorectal cancer: a nationwide Japanese study.

BACKGROUND: The clinicopathological features of ulcerative colitis-associated colorectal cancer (UC-CRC) have not yet been fully clarified, especially in Asian populations. This study aimed to clarify the prognosis and clinicopathological features of UC-CRC in comparison with sporadic CRC in the Japanese population. METHODS: Histologically diagnosed UC-CRC patients between 1978 to 1998 were extracted from the Multi-Institutional Registry of Large-Bowel Cancer in Japan, a large nationwide CRC database, and the clinicopathological features and postoperative survival rates of UC-CRC patients and sporadic CRC patients were compared. RESULTS: Among the 108,536 CRC patients registered between 1978 and 1998, a total of 169 UC-CRC patients were identified, including 121 patients who had been treated surgically. The proportion of UC-CRC patients increased in the period between 1995 and 1998 compared to that between 1978 and 1994. Comparisons with the sporadic CRC patients showed that the UC-CRC patients were younger, had a higher proportion of multiple cancer lesions, had higher proportions of superficial type lesions and invasive type lesions morphologically, and had higher proportions of mucinous or signet ring cell carcinomas. In stage III, UC-CRC patients had a poorer survival rate than the sporadic CRC patients (43.3% versus 57.4%, P = 0.0320). CONCLUSIONS: UC-CRC increased over the investigated time periods and showed a poorer survival than sporadic CRC in the advanced stage, while no difference was observed in the early stage. By detecting UC-CRC at an early stage we can expect a similar postoperative outcomes to that of sporadic CRC. These results stress the importance of surveillance for the early detection of UC-CRC.

RUNX3 copy number predicts the development of UC-associated colorectal cancer.

RUNX3 is a tumour suppressor gene that plays an important role in the development of various cancers. The present study aimed to compare RUNX3 mRNA expression levels and DNA copy numbers in the non-neoplastic rectal mucosa between ulcerative colitis (UC) patients with and without UC-associated colorectal cancer (UC-Ca). We further aimed to build a predictive model of the development of UC-Ca based on the RUNX3 DNA copy number. RUNX3 mRNA expression levels were quantified by RT-PCR. The hypermethylation and DNA copy number of RUNX3 were also determined. Thirty-five UC patients were examined, 17 of whom had UC-Ca (UC-Ca group) and 18 who did not (UC-NonCa group). The UC-Ca group had significantly lower mRUNX3 expression levels and smaller DNA copy numbers than the UC-NonCa group (p=0.04, p=0.0016, respectively). RUNX3 expression levels correlated with DNA copy numbers. Classification of the UC-Ca and UC-NonCa group based on DNA copy number gave an accuracy of 82.9%. RUNX3 expression levels in the non-neoplastic rectal mucosa was significantly decreased in the UC-Ca group and it is suggested that this was attributable to the decrease in RUNX3 DNA copy number. The present predictive model may be useful in the selection of high risk UC-Ca patients and to improve the efficacy of surveillance colonoscopy. The present study suggests that RUNX3 might play an important role in the development of UC-Ca.

Gene expression of mesenchyme forkhead 1 (FOXC2) significantly correlates with the degree of lymph node metastasis in colorectal cancer.

In stage III colorectal cancer, patients with N1 stage tumors show poorer outcome than patients with N2 stage tumors. Our objective was to identify genes that are predictive for the presence of lymph node metastasis, and to characterize the aggressiveness of lymph node metastases. Gene expression profiles of colorectal cancer were determined by microarray in training (n = 116) and test (n = 25) sets of patients. We identified 40 discriminating probes in patients with and without lymph node metastases. Using these probes, we could predict the presence of lymph node metastasis with an accuracy of 87.1% (training set) and 76.0% (test set). Among discriminating probes, FOXC2 expression was significantly correlated with the degree of lymph node metastasis. FOXC2 was expressed significantly and disparately in patients with N1 and N2 stage tumors as analyzed by real-time reverse transcriptase-polymerase chain reaction. FOXC2 appears to be involved in determining the aggressiveness of lymph node metastasis in colorectal cancer.

Preoperative chemoradiation and extended pelvic lymphadenectomy for rectal cancer: Two distinct principles.

Extended pelvic lymphadenectomy (EPL) with total mesorectal excision (TME) has been reported to provide oncological benefit in lower rectal cancer in Japan. In Western countries EPL is not widely accepted because of frequent morbidity but instead preoperative chemoradiation (CRT) followed by TME has been established as a standard treatment for decreasing local recurrence. Recently, several studies have focused on the comparison between these two distinct therapeutic approaches in Western countries and Japan. A study comparing Dutch trial data and Japanese data revealed that EPL and RT are almost equivalent in decreasing local recurrence in lower rectal cancer as compared with TME alone. Considering that almost 45% survival can be achieved by EPL even in the presence of metastatic lateral lymph nodes (LLNs), EPL performed by experienced surgeons definitely contributes to decrease local recurrence. On the other hand, a randomized controlled trial in Japan that compared EPL with conventional TME following preoperative RT revealed that EPL is associated with a higher frequency of sexual and urinary dysfunction without oncological benefits in the presence of preoperative RT. On this point, preoperative CRT followed by conventional TME without EPL would be a better therapeutic approach in patients without evident metastatic LLNs. For future treatment, it would be desirable to have a narrower indication for EPL using full advantage of recent improvement in image diagnosis. Although objective comparison of these two principles between Japan and the West is difficult due to differences in patient groups, further studies would lead to the next great step towards future improvement in treating lower rectal cancer.

Treatment of colorectal carcinoids: A new paradigm.

It is often difficult to evaluate the grade of malignancy and choose an appropriate treatment for colorectal carcinoids in clinical settings. Although tumor size and depth of invasion are evidently not enough to stratify the risk of this rare tumor, the present guidelines or staging systems do not mention other clinicopathological variables. Recent studies, however, have shed light on the impact of lymphovascular invasion on the outcome of colorectal carcinoids. It has been revealed that the presence of lymphovascular invasion was among the strongest risk factors for metastasis along with tumor size and depth of invasion. Furthermore, tumors smaller than 1 cm, within submucosal invasion and without lymphovascular invasion, carry minimal risk for metastasis with 100% 5-year survival in the studies from Japan as well as from the USA. This would suggest that these tumors could be curatively treated by endoscopic resection or transanal local excision. On the other hand, colorectal carcinoids with either lymphovascular invasion or tumor size larger than 1 cm carry the risk for metastasis equivalent to adenocarcinomas. Therefore, it should be emphasized that histological examination of lymphovascular invasion is mandatory in the specimens obtained by endoscopic resection or transanal local excision, as this would provide useful information for determining the need for additional radical surgery with regional lymph node dissection. Although the present guidelines or TNM staging system do not mention the impact of lymphovascular invasion, this would be among the next promising targets in order to establish better guidelines and staging systems, particularly in early-stage colorectal carcinoids.

Current status in the occurrence of postoperative bleeding, perforation and residual/local recurrence during colonoscopic treatment in Japan.

Bleeding, perforation, and residual/local recurrence are the main complications associated with colonoscopic treatment of colorectal tumor. However, current status regarding the average incidence of these complications in Japan is not available. We conducted a questionnaire survey, prepared by the Colorectal Endoscopic Resection Standardization Implementation Working Group, Japanese Society for Cancer of the Colon and Rectum (JSCCR), to clarify the incidence of postoperative bleeding, perforation, and residual/local recurrence associated with colonoscopic treatment. The total incidence of postoperative bleeding was 1.2% and the incidence was 0.26% with hot biopsy, 1.3% with polypectomy, 1.4% with endoscopic mucosal resection (EMR), and 1.7% with endoscopic submucosal dissection (ESD). The total incidence of perforation was 0.74% (0.01% with the hot biopsy, 0.17% with polypectomy, 0.91% with EMR, and 3.3% with ESD). The total incidence of residual/local recurrence was 0.73% (0.007% with hot biopsy, 0.34% with polypectomy, 1.4% with EMR, and 2.3% with ESD). Colonoscopic examination was used as a surveillance method for detecting residual/local recurrence in all hospitals. The surveillance period differed among the hospitals; however, most of the hospitals reported a surveillance period of 3-6 months with mainly transabdominal ultrasonography and computed tomography in combination with the colonoscopic examination.