Search

Purpose: The aim of this study is to identify gene expression signatures that accompany dedifferentiation at the cancer invasion front in colorectal cancer.Experimental Design: Two types of colorectal cancer were selected. Both types were well-differentiated adenocarcinomas at the superficial lesion. One type showed a dedifferentiated phenotype at the invasion front (type A, 13 samples); the other showed almost no dedifferentiated cancer cells at the invasion front (type B, 12 samples). Laser microdissection was combined with a cDNA microarray analysis to investigate the superficial lesions and the invasion front in colorectal cancers.Results: Eighty-three genes were differentially expressed between types A and B in the superficial lesions, and the samples of superficial lesions were divided correctly into two clusters by these genes. Interestingly, the samples of the invasion front were also divided into the two same clusters by these genes. The text mining method selected 10 genes involved in potential mechanisms causing dedifferentiation of cancer cells at the invasion front. The potential mechanisms include the networks of transforming growth factor-β, Wnt, and Hedgehog signals. The expression levels of 10 genes were calculated by quantitative reverse transcription-PCR and 8 genes were confirmed to be significantly differentially expressed between two types (P < 0.05). The gene expression profiles of 8 genes divided 12 test cases into two clusters with one misclassification.Conclusions: The molecular mechanisms constructed with 8 genes from three networks of transforming growth factor-β, Wnt, and Hedgehog signals were found to correlate with dedifferentiation at the invasion front of colorectal cancer.

Activating mutations in the ABCC8 gene cause diabetes and inactivating mutations usually cause hyperinsulinemic hypoglycemia in infancy. Patients with hypoglycemia in infancy due to a heterozygous inactivating mutation have been reported to occasionally progress to diabetes later in life. We explored the gene responsible for diabetes in two brothers, who were suspected to have diabetes at 15 and 18 years‐of‐age, respectively, with whole exome sequencing, and identified a compound heterozygous ABCC8 gene mutation (p.Arg168Cys and p.Arg1421Cys). Although their father and mother were heterozygous carriers of the p.Arg168Cys and the p.Arg1421Cys mutation, respectively, neither parent had diabetes. These mutations have been reported to be responsible for hypoglycemia in infancy and function as an inactivating mutation. Our results suggest that the inactivating ABCC8 gene mutation is also important in the etiology of diabetes., Pedigree of a family with young‐onset diabetes due to a compound heterozygous inactivating ABCC8 gene mutation (p.Arg168Cys and p.Arg1421Cys). These mutations had been reported to be responsible for hypoglycemia in infancy and be functional inactivating mutations.

Risks for postoperative small bowel obstruction have been demonstrated in several reports, most of which indicated male sex was a risk factor, but with the reason remaining unknown. We tested the hypothesis that it could be because males have more visceral fat than females. This prospective observational study aims to examine risks of early postoperative small bowel obstruction (EPSBO) after colorectal cancer surgery and the association between visceral to subcutaneous fat area ratio (V/S ratio) and EPSBO.Four hundred and seventy-four patients who underwent colectomy for colorectal cancer in our hospital were enrolled in this study. The influence of several factors including V/S ratio on the development of EPSBO was analyzed.Thirty-one of the 474 patients (6.5%) developed EPSBO. EPSBO occurred more frequently in males (p = 0.03) and cases who developed postoperative anastomotic leakage (p 0.001) or wound infection (p = 0.02). Higher V/S ratio was strongly related to male sex (p 0.001). Multivariate analysis revealed higher V/S ratio (OR 2.25; p = 0.049) and anastomotic leakage (OR 5.86; p 0.001) were independent risk factors for EPSBO.Higher V/S ratio was significantly related to EPSBO, suggesting that one of the reasons EPSBO was more likely to occur in males because they have more visceral fat than females. Preoperative identification of this risk factor could help us watch out for this potential complication.

Background Early postoperative small bowel obstruction (EPSBO) is one of the most common complications after colorectal cancer (CRC) surgery, and clarification of its causes is desired. Several reports have demonstrated the risks of EPSBO, but few have focused on laparoscopic surgery for CRC and intraoperative maneuvers. We therefore prospectively examined the risk factors for EPSBO after laparoscopic CRC resection. Methods We prospectively enrolled 706 patients with CRC that underwent laparoscopic CRC resection in our hospital and affiliated hospitals. We analyzed several factors concerning EPSBO including intraoperative procedures. Results EPSBO developed in 43 of the 706 cases (6.1%). Univariate analysis showed that risk factors for EPSBO were male sex, increased operative time, repositioning of the small intestine before wound closure and anastomotic leakage. Risk factors for EPSBO according to multivariate analysis were increased operative time (odds ratio (OR) 2.41; P = 0.032), repositioning of the small intestine before wound closure (OR 3.58; P = 0.005) and anastomotic leakage (OR 3.91; P = 0.006). Conclusion To reduce EPSBO after laparoscopic CRC surgery, the operation should be finished as soon as possible without performing optional maneuvers. To avoid development to EPSBO, particular care is required in cases where the risk of anastomotic leakage is predicted to be high.

Background Defaecatory function is often poor after anterior resection. Denervation of the neorectum following high ligation of the inferior mesenteric artery (IMA) is a possible cause of impaired defaecatory function. The purpose of this randomized clinical trial was to clarify whether the level of ligation of the IMA in patients with rectal cancer affects defaecatory function. Methods Between 2008 and 2011, patients who underwent anterior resection for rectal cancer were randomized to receive either high or low ligation of the IMA. The primary endpoint was to demonstrate the superiority of low ligation in terms of defaecatory function. Results One hundred patients were enrolled in the study; 51 were randomized to high ligation of the IMA and 49 to low ligation. There were no differences between the groups in terms of clinical data, except tumour stage, which was more advanced in the high-ligation group (P = 0·046). Nor were there any differences in defaecatory function, self-assessment of defaecation, Faecal Incontinence Quality of Life scale or continence score between groups at 3 months and 1 year. The number of harvested lymph nodes was similar. The rate of symptomatic anastomotic leakage was 16 per cent in the high-ligation group and 10 per cent in the low-ligation group (P = 0·415). Conclusion The level of ligation of the IMA in patients with rectal cancer did not affect defaecatory function or the incidence of postoperative complications. Registration number: NCT00701012 (http://www.clinicaltrials.gov).

This study evaluated the impact of obesity on learning to perform laparoscopic surgery for colon cancer.We compared the outcomes for 72 patients with colon cancer treated by a single surgeon between June 2005 and July 2008. The first 36 patients who underwent surgery were considered to be during the "early period," and the other 36 patients who underwent surgery as the "late period," and the patients with a body mass index (BMI) ≥25 kg/m(2) were defined as being obese.During the early period, the tumor stages of obese patients were less advanced than those of nonobese patients, whereas the length of the operation, surgical blood loss, and wound diameter of obese patients were worse than those of nonobese patients. Furthermore, the tumor stages in the obese patients during the late period were more advanced than those in obese patients during the early period, whereas the length of the operation and number of dissected lymph nodes in the obese patients during the late period were better than those in obese patients during the early period.We demonstrated that the differences of the surgical outcomes between obese and nonobese patients undergoing laparoscopic colon resection decreased as the surgeon's experience increased.

BACKGROUND: A laparoscopic low anterior resection with double-stapling technique for lower rectal cancer is considered to be technically challenging because it is difficult to perform rectal transection and anastomosis in the narrow pelvic cavity. METHODS: We developed a new method for transecting the rectum with stapling a small number of cartridges. In laparoscopic low anterior resection, a 70-mm endovascular clip clamps the rectal wall at the anal side of the tumor. An endolinear stapler is applied at the rectal wall parallel and caudal to the 70-mm endovascular clip. A Nelaton catheter of 3.5 to 4.5 mm in outer diameter is inserted, and the loop of the Nelaton catheter is made behind the rectum. The Nelaton catheter loop is applied at the rectal wall parallel and caudal to the endolinear stapler and is pulled parallel the endolinear stapler toward the anterior side of the rectum. The endolinear stapler with opened jaws can be pushed deeper into the space, then the jaws can be closed in a position that can transect the rectum with one firing using only one cartridge. RESULTS: Curative low anterior resection with rectal transection using the Nelaton catheter pulling method was performed in 13 patients with rectal cancer. The median value and range of tumor distance from the anal verge were 6.0 and 4.5 to 10.0 cm. The median duration of the operation was 284 minutes, and median blood loss was 10 mL. The number of stapling cartridges used for rectal transection was 1 in all cases, and there were no major complications. CONCLUSIONS: We have demonstrated a safe, easy, and effective new transection method for rectal cancer resection using one firing with a Nelaton catheter.

症例は86歳の男性で，便秘と腹部膨満感を主訴に近医を受診した．下部消化管内視鏡検査にて盲腸に腫瘍を認めたため当院紹介となった．CTにて肝両葉に多数の肝転移を認めた．イレウスにて緊急手術となり，回盲部切除，D2郭清を施行した．術後，病理組織学的検査所見では虫垂構造を中心に病変がみられ，小細胞癌の様相を呈していた．また，一部虫垂と思われる部位に，粘液産性，管状構造を呈する粘液嚢胞腺癌の像が認められ，虫垂原発の小細胞癌と粘液嚢胞腺癌の混合腫瘍と診断された．術後経過は良好であったが，病状が急速に進展し，術後54日で死亡した．病理組織学的に腺癌，小細胞癌の両腫瘍成分が混在し，腺癌成分はSynaptophysin染色検査で陽性を示すことから，腺癌から小細胞癌への分化の潜在性を有すると考え，両腫瘍成分は同一起源である可能性が考えられた．今回，このまれな虫垂原発の小細胞癌と粘液嚢胞腺癌が混合した腫瘍について報告する．

Background: The prognosis of T1 plus T2 stage III rectal cancer patients is better than that of T3 stage III rectal cancer patients. However, it is thought that T1 rectal cancer patients have a better prognosis than T2 rectal cancer patients. Aim: This study attempted to clarify the difference of the short- and long-term outcomes in T2 and T3 stage III rectal cancer patients deleting T1 cancer. Methods: The study demonstrated the potential predictors of the survival after surgery, the factors associated with T3 and T2, and the recurrence sites in 134 patients with stage III rectal cancer who underwent surgery, including 111 patients with T3 and 23 patients with T2. Results: The disease-free survival (DFS) of the T3 stage III patients was worse than the T2 stage III patients (5-year DFS rates, 52 vs. 78%; 10-year DFS rates, 43 vs. 78%; p =0.044). The maximum tumor size and operative blood loss were significant tumor characteristics associated with the depth of invasion (p =0.007,p =0.011,respectively). There was no significant difference in the recurrence sites after surgery between the two groups. Conclusion: As a result, a more detailed subdivision for stage III rectal cancer is considered necessary.

Preoperative assessment of the lateral pelvic lymph nodes is important for treatment strategy to patients with lower rectal cancer. Fifty-three patients with primary lower rectal cancer were preoperatively assessed by spiral computed tomography (CT) and magnetic resonance imaging (MRI) at 1.5 T with a phased-array coil. Preoperative tumor and lymph node stages were compared with the final histological findings. The MRI tumor stage coincided with the histological stage in 36 of 53 patients (68%). The MRI and CT lymph node stage coincided with the histological stage in 33 (62%) and 26 (49%) of 53 patients, respectively. However the accuracy of MRI in detecting the lateral pelvic lymph node involvement was 83%, compared to 77% of CT (p

症例は73歳,男性. 1999年4月,体重減少と食欲不振にて近医を受診し,胆嚢癌を疑われた.腹部US, CT, ERCPにて胆嚢底部に腫瘍および肝S4, S5への直接浸潤を認めた.胃透視,内視鏡, EUSで胃壁および十二指腸球部から下行脚に直接浸潤を疑わせる所見も認めた. 1999年6月に手術を施行した.腫瘍は胆嚢底部原発で肝右葉に浸潤していたものの,胃と十二指腸への浸潤はなかったが,左上腹部腹膜に腹膜播種を疑う結節を認め,術中迅速病理検査に提出したところundifferenciated carcinomaであったため,胆摘・肝床部切除にとどめ,手術を終了した.術後の病理組織学診断ではneuroendo-crine carcinomaで,免疫組織染色ではNSEが陽性であった.患者は術後6カ月後に死亡した.胆嚢原発内分泌細胞癌の1例を経験したのでここに報告する.

PURPOSE This study evaluated the impact of the pelvic pillow on a single surgeon's learning how to perform laparoscopic low anterior resection (LAR) for rectal cancer. METHODS We compared the outcomes for 23 patients with rectal cancer including the first 11 patients who underwent laparoscopic LAR without the pelvic pillow, and the latter 12 patients with the pelvic pillow by a single surgeon. RESULTS The stage of the pelvic pillow (+) was more advanced than that of the pelvic pillow (-). The length of the operation and postoperative start of oral intake for the pelvic pillow (+) were shorter and earlier than those of the pelvic pillow (-). The pelvic surgical field in the pelvic pillow (+) was better and allowed better evaluation than the pelvic pillow (-). CONCLUSIONS Maintaining an excellent view of the pelvic surgical field with the pelvic pillow might have an impact on learning laparoscopic LAR.

This study demonstrated the usefulness of the post/preoperative serum carcinoembryonic antigen (CEA) ratio as a predictor of survival after surgery for stage III rectal cancer patients. One hundred and four patients with stage III rectal cancer who underwent surgery between 1991 and 2000 were enrolled. The ratio of the postoperative serum CEA value divided by the preoperative serum CEA value was defined as post/preoperative serum CEA ratio, and the patients were separated into two groups: post/preoperative serum CEA ratio ≤1 (n = 86) and >1 (n = 18). The multivariate analyses demonstrated that the intraoperative blood loss, lack of a sphincter-saving procedure and a post/preoperative serum CEA ratio >1 were independent factors predicting a poor prognosis for the overall and disease-free survival. The overall and disease-free survival rates among patients with a high preoperative serum CEA level (>5 ng/ml) or patients with a high postoperative serum CEA (>5 ng/ml) were longer in patients with a post/preoperative serum CEA ratio ≤1, in comparison to those with a post/preoperative serum CEA ratio >1. Liver metastasis was observed more frequently in patients with a post/preoperative serum CEA ratio >1. The post/preoperative serum CEA ratio may be a predictor of the prognosis after surgery for stage III rectal cancer patients.

Background The identification of molecular markers that are useful for predicting lymph node metastasis is urgently needed to determine treatment strategies for T1 colorectal cancer (CRC). We previously showed that 10 candidate genes are correlated with de-differentiation at the invasion front of CRC using a gene expression analysis. These 10 genes are potential markers that may predict lymph node metastasis by CRC. Materials and methods Samples were obtained from 161 patients with CRC. Quantitative real-time reverse transcription-polymerase chain reaction assays were performed using 66 T3 samples in order to extract genes correlated with lymph node metastasis. Immunohistochemical studies of the extracted genes were performed on 66 T3 and 95 T1 samples. A univariate analysis followed by a multivariate logistic regression model was used to examine independent risk factors for lymph node metastasis. Results The CITED1 messenger RNA expression was found to be an independent risk factor for lymph node metastasis in T3 CRC patients ( P = 0.040). A high CITED1 protein expression, as detected with immunohistochemistry, was also an independent risk factor in T3 CRC patients ( P = 0.035). In T1 colorectal cancer patients, a high CITED1 protein expression was found to be an independent risk factor for lymph node metastasis ( P = 0.010). The positive predictive and negative predictive values in the T1 colorectal cancer patients were 27.5% and 95.5%, respectively. Conclusions The CITED1 expression is correlated with lymph node metastasis in patients with CRC. In T1 colorectal cancer patients, CITED1 has the potential ability to predict the presence of lymph node metastasis.

The purpose of this study was to show the clinical features of up-front surgery of the primary tumor in asymptomatic patients with incurable colorectal PC.Forty-six patients that were diagnosed between 1998 and 2007 with asymptomatic colorectal PC who could not be successfully cured by surgery were assessed retrospectively.A univariate analysis revealed the presence of liver metastases, without the use of oxaliplatin (OX)/irinotecan (IRI) and without a primary tumor resection to be poor prognostic factors for survival (p = 0.044, p = 0.030, p0.001, respectively). According to a multivariate analysis, no use of OX/IRI and no primary tumor resection, were found to be independent poor prognostic factors for survival (HR 2.57; p = 0.047, HR 6.62; p = 0.003, respectively). The median survival time of patients treated with and without OX/IRI was 18 and 7 months, respectively. The median survival time of patients with and without primary tumor resection was 10 and 2 months, respectively. The number of patients needing surgical intervention for intestinal obstruction after surgery significantly increased in patients treated with OX/IRI (p = 0.001).Improvement of survival may be related to widespread use of modern systemic chemotherapy and primary tumor resection. However, an increased number of patients that needed surgery for an intestinal obstruction were observed, even after up-front surgery, when patients were treated with modern systemic chemotherapy.

Laparoscopic surgery for colorectal disease has become widespread as a minimally invasive treatment. This is important because the increasing availability of new devices allows us to perform procedures with a reduced length of surgery and decreased blood loss. We herein report the results of a literature review of energy sources for laparoscopic colorectal surgery, focused especially on 6 studies comparing ultrasonic coagulating shears (UCS) and other instruments. We also describe our laparoscopic dissection techniques using UCS for colorectal cancer. The short-term outcomes of surgeries using UCS and Ligasure for laparoscopic colorectal surgery were superior to conventional electrosurgery. Some authors have reported that the length of surgery or blood loss when Ligasure was used for laparoscopic colorectal surgery is less than when UCS was used. On the other hand, a recent study demonstrated that there were no significant differences between the short-term outcomes of UCS and Ligasure for laparoscopic colorectal surgery. It is therefore suggested that the choice of technique used should be made according to the surgeon’s preference. We also describe our laparoscopic dissection techniques using UCS (Harmonic ACE) for colorectal cancer with regard to the retroperitoneum dissection, dissection technique, dissection technique around the feeding artery, and various other dissection techniques. We therefore review the outcomes of using various energy sources for laparoscopic colorectal surgery and describe our laparoscopic dissection techniques with UCS (Harmonic ACE) for colorectal cancer.

Background The differences between the metastatic property of moderately (Mod) and well (Wel) differentiated colorectal adenocarcinoma remain unclear. Since Mod is unable to form complete acini, therefore an epithelial-mesenchymal transition (EMT) can occur in that structure. Herein, we hypothesized that Mod metastasizes more easily than the Wel counterparts. Methods The medical records of 283 consecutive patients with Mod (n = 71) or Wel (n = 212) who underwent surgery were reviewed between January 1, 2001, and December 31, 2003, for actual 5-year overall survival. We examined the differences between the clinicopathological characteristics of the Mod and the Wel groups. Results The lymph node involvement (p < 0.0001), lymphatic permeation, venous permeation, depth of invasion, liver metastasis, and carcinomatous peritonitis were significantly higher in the Mod group in comparison to the Wel group. The independent risk factors by a logistic regression analysis for lymph node involvement were as follows: lymphatic permeation, liver metastasis, and Mod (p = 0.0291, Relative Risk of 1.991: 95% Confidence Interval: 1.073-3.697). A Kaplan-Meier survival curve showed that Mod had a trend towards a poor survival (p = 0.0517). Conclusion Mod metastasizes to the lymph nodes more easily in comparison to Wel. Therefore, patients with Mod may be considered the existence of lymph node involvement.

Anastomotic recurrence after an anterior resection for rectal cancer has not been analyzed in detail in the era of total mesorectal excision. This study tried to clarify the characteristics of patients with anastomotic recurrence when compared to the pelvic recurrence. This study compared the clinicopathological data of 21 isolated recurrent patients that were treated between 1998 and 2007, including eight with anastomotic recurrence and 13 with pelvic recurrence. The rate of positive serum carcinoembryonic antigen level at the time of recurrence is 0% in the anastomotic recurrence group and 85% in the pelvic recurrence group (p

There are increasing reports showing the clinical significance of the p53 polymorphism status in terms of the response to chemotherapy. We investigated whether p53 polymorphism and mutation were associated with in vitro sensitivity to 5-fluorouracil (5-FU) in patients with colorectal cancer. Chemosensitivity to 5-FU was evaluated by the collagen gel droplet embedded culture drug sensitivity test. 5-FU sensitivity of tumor cells without inactive p53 mutation in the arginine/arginine (Arg/Arg) variant was significantly higher than that of tumor cells with or without inactive p53 mutation in other variants (p = 0.022), whereas the 5-FU sensitivity of tumor cells with inactive p53 mutation in the Arg/Arg variant was significantly lower than that of tumor cells with or without inactive p53 mutation in other variants (p = 0.002). In the Arg/Arg variant, apoptotic cells induced by 5-FU treatment in patients without inactive p53 mutation were more markedly increased than those in patients with inactive p53 mutation (p = 0.037). Bax and Bcl-2 protein expressions in tumor tissue treated with 5-FU were associated with both 5-FU sensitivity and the apoptotic cell count. Our data show that the Arg/Arg genotype without inactive p53 mutation could be predictive of a more favorable response and the Arg/Arg genotype with inactive p53 mutation a less favorable response to chemotherapy using 5-FU in CRC. The combination of the p53 codon 72 polymorphism and p53 mutation status is a potential predictive marker of sensitivity to 5-FU in CRC.

The prognosis of T1 plus T2 stage III rectal cancer patients is better than that of T3 stage III rectal cancer patients. However, it is thought that T1 rectal cancer patients have a better prognosis than T2 rectal cancer patients.This study attempted to clarify the difference of the short- and long-term outcomes in T2 and T3 stage III rectal cancer patients deleting T1 cancer.The study demonstrated the potential predictors of the survival after surgery, the factors associated with T3 and T2, and the recurrence sites in 134 patients with stage III rectal cancer who underwent surgery, including 111 patients with T3 and 23 patients with T2.The disease-free survival (DFS) of the T3 stage III patients was worse than the T2 stage III patients (5-year DFS rates, 52 vs. 78%; 10-year DFS rates, 43 vs. 78%; p =0.044). The maximum tumor size and operative blood loss were significant tumor characteristics associated with the depth of invasion (p =0.007,p =0.011,respectively). There was no significant difference in the recurrence sites after surgery between the two groups.As a result, a more detailed subdivision for stage III rectal cancer is considered necessary.

This report is an attempt to clarify the effect of diabetes mellitus on perineal wound complications including infectious entities and delayed wound healing after abdominoperineal resection and also tried to show the risk factors for perineal wound complications. The data of 80 patients who underwent an abdominoperineal resection were reviewed from April 1996 to March 2006. The rate of perineal wound complications is higher in diabetics (67%) than in nondiabetics (18%, p = 0.005). In a multivariate analysis, diabetes mellitus and operation time (≥420 min) were the risk factors for perineal wound complications (p = 0.040, p = 0.027, respectively). Infectious perineal wound complication was associated with diabetes mellitus (p

A hepatectomy is the only treatment offering long-term survival in patients with colorectal liver metastases. However, 70-80% of the patients with a complete resection develop recurrent disease after an initial hepatectomy. Sixty-one patients who underwent metastases from colorectal carcinoma with a curative hepatectomy were entered into this study. Recurrence after hepatectomy was observed in 41 patients (67.2%). We reviewed the outcome of these 41 patients. Repeat reduction surgery was performed on 16 out of 41 patients (39.0%). According to a multivariate analysis, repeat reduction surgery and tumor size were found to be independent prognostic factors for the survival rate (p=0.007, p=0.018). Furthermore, in the group that underwent repeat reduction surgery, the rate of positive lymph nodes was significantly lower in the primary lesions, and the disease-free interval (DFI) was also significantly longer than in the group that did not undergo repeat reduction surgery (p=0.023, p=0.045), respectively. Repeat reduction surgery was found to be the most important prognostic factor. Patients with a longer DFI and with negative lymph node findings at the primary site may therefore be considered to be good candidates for repeat reduction surgery.

It is difficult to establish a clear-cut indication for rectal surgery in elderly patients because of greater risk. We tried to clarify the factors associated with the short-term and long-term outcomes between elderly and younger patients.We clarified the potential predictors of the cancer-related and disease-free survivals after surgery, the factors associated with the elderly, preoperative comorbid conditions, and postoperative complications in 158 patients with stage III rectal cancer who underwent surgery, including 33 elderly patients (or=75 years) and 125 younger patients (75 years).An old age and macroscopic types 3 and 4 were independent poor prognostic factors of cancer-related survival, whereas the disease-free survival of the younger patients was not longer than for the elderly patients. Interestingly, the survival rate in the elderly patients with recurrence was shorter than that in the younger patients. Histopathological type except well differentiated and without chemotherapy were significant tumor characteristics associated with the elderly patients. On preoperative comorbid conditions, elderly patients have more cardiovascular diseases than younger patients, whereas there were no significant differences in the postoperative complications.Strength of the adjuvant and intensive therapies after recurrence may contribute to gain long-term survival in the elderly rectal cancer patients.

Liver resection has been recognized as the best treatment for patients with colorectal liver metastases, but as a curative resection for multiple and bilobar colorectal liver metastases (MBCLM) it is definitely less effective. We clarify predictors of survival for unresectable MBCLM. Potential predictors of overall survival, and the correlation between tumor marker and survival were evaluated for patients with synchronous unresectable MBCLM, including 6 rectal and 17 colon cancers. In univariate analysis, survival in patients with the following parameters were longer than those without them: number of liver metastases (/=10), without lung metastasis and peritoneal invasion, and with a1.0 ratio of postoperative CEA/preoperative CEA. In multivariate analysis, the numbers of liver metastases (10) and a1.0 ratio of postoperative CEA/preoperative CEA were factors of poor prognosis, and patients with two such factors had an even worse prognosis. There was a tendency for correlation between the ratio of postoperative CEA/pre-operative CEA and survival (R=-0.492, P=0.053; y=17.388-3.733x). Thus, we clarified some of the predictors of survival for MBCLM, and the usefulness of serum CEA.

Dihydropyrimidine dehydrogenase (DPD) is considered to be a key enzyme affecting the prognosis for patients with colorectal cancer. We investigated whether a correlation exists between the expression of DPD and survival in patients with colorectal cancer. The present study was designed to quantify the DPD level using an enzyme-linked immunosorbent assay in tumors and normal tissue specimens obtained from 22 colorectal cancer patients. There were no significant differences in the preoperative features, neither in the intra- and post-operative findings of patients between the high DPD and low DPD groups in tumor tissue. In patients showing an expression of DPD in tumor tissue, the overall survival in the low DPD group tended to be longer than that in the high DPD group (P = 0.076). In contrast, in patients showing an expression of DPD in normal tissue, no significant difference was observed in the overall survival between the high DPD and low DPD groups (P = 0.358). In patients showing an expression of DPD in tumor tissue, the disease-free survival in the low DPD group was longer than that in the high DPD group (P = 0.046), whereas in patients showing an expression of DPD in normal tissue, no significant difference was seen in the disease-free survival between the high DPD and low DPD groups (P = 0.473). There tended to be a correlation between the DPD expression in tumor tissue and that in adjacent normal tissue (R = 0.390, P = 0.073). Based on these findings, we demonstrated the importance of DPD expression in tumor tissue as a prognostic factor in patients with colorectal cancer.

Patients with stage III colorectal cancer have a substantial risk of microscopic metastatic disease at the time of resection. Treatment with leucovorin (LV)/5-Fluorouracil (5FU) has been demonstrated to be effective for advanced colorectal cancer; however, the clinical impact of l-LV/5FU is still unclear. 1-LV/5FU for patients with stage III colorectal cancer may play an important role, as an adjuvant chemotherapy, in improving survival.The clinicopathological features of 36 patients receiving adjuvant l-LV/54 administration and 16 not, univariate analysis of potential predictors of overall survival and disease-free survival, relative risk of overall survival and disease-free survival by multivariate analysis and the occurrence of chemotherapy-induced toxic effects were studied in 52 patients with stage III colorectal cancer, including 30 with rectal and 22 with colon cancer, who had undergone surgery.No significant differences were found in the clinicopathological features of the 2 groups. On univariate analysis, there were no significant differences in overall survival in either group; disease-free survival in patients with adjuvant I-LV/5FU was longer than that in patients without it (p0.001). Moreover, multivariate analysis demonstrated that I-LV/5FU adjuvant chemotherapy was an independent prognostic factor in terms of disease-free survival (p =0.001; RR, 17.492; 95% CI, 3.298-92.778).I-LV/5FU adjuvant chemotherapy in patients with stage III colorectal cancer is important as an independent prognostic factor in terms of disease-free survival.

The prognosis of patients with colorectal cancer is considered to be affected by several factors. Recently, chemotherapy for this disease has been demonstrated to be effective for long-term survival. In this study, the potential predictors, including chemotherapy regimens for survival after surgery, in patients with stage IV colorectal cancer are presented.Univariate and multivariate analyses of potential predictors of survival after surgery were carried out for 56 patients with stage IV colorectal cancer who had undergone surgery, including 22 with rectal and 34 with colon cancer.The survival in patients who had had a primary liver resection was longer than that in patients who had not (p=0.007). There was a significant difference among chemotherapy regimens (p=0.021). The survival in patients who were administered l-leucovorin/5-fluorouracil (l-LV/5FU) was longer than that in patients who received uracil-tegafur (UFT) and cisplatin (CDDP)/5FU (p=0.024, p=0.004, respectively). In multivariate analyses, there were 5 favorable factors that influenced overall survival after surgery: lymph node metastasis (p=0.029), no bone metastasis (p=0.012), no peritoneal invasion (p=0.018), no primary liver resection (p=0.004) and the chemotherapy regimen (p=0.008). Furthermore, the survival in patients with a continued l-LV/5FU plus modified IFL regimen (additional irinotecan) was longer than for those patients who received other regimens, in both univariate and multivariate analyses.Five factors, namely lymph node metastasis, bone metastasis, peritoneal invasion, primary liver resection and chemotherapy, are potential predictors of survival after surgery for patients with stage IV colorectal cancer.

We experienced three cases of postoperative hemorrhage from a stapled gastrointestinal anastomosis, and established endoscopic microwave coagulation therapy (EMCT) with a cylinder-type electrode. We were able to treat postoperative hemorrhage over the entire circumference of stapled anastomosis successfully. Two patients had undergone a lower third thoracic esophagogastrectomy through a left thoraco-abdominal approach for gastric cancer in the cardia, while the other case had undergone Billroth I gastrectomy. They each had fresh bleeding from the stapled anastomosis after the operation. Emergency endoscopic examination was immediately performed. Endoscopy revealed bleeding on the suture line. We performed hemostasis endoscopically with microwave coagulation therapy safely. They were discharged from the hospital without complications such as leakage and stenosis. Since EMCT with the cylinder-type electrode can coagulate shallowly and widely, it is very effective for hemorrhage from a stapled anastomosis.

l-leucovorin (LV)/5-fluorouracil (5FU) may play an important role, as an adjuvant chemotherapy, in improving the survival of patients with stage III colorectal cancer. However, severe toxicity of the chemotherapeutic agent could be fatal. Adverse effects, including bone marrow suppression, liver damage, renal damage, and glucose tolerance, were evaluated daily during 3 courses of l-LV/5FU-modified RPMI regimen adjuvant chemotherapy for 22 patients with stage III colorectal cancer. Decrease in the serum levels of neutrophils and platelets occurred in the 1st course, which became more obvious after three or four administrations of l-LV/5FU in the 1st course. Furthermore, serum levels of leukocytes, neutrophils, and platelets on the re-start day of this chemotherapy after 2-week intervals were lower than those on the start day of this chemotherapy. In the evaluation of liver damage, renal damage, and glucose tolerance; serum alanine aminotransferase level in the 2nd course, serum total bilirubin (T.Bil) level in the 1st course, and serum creatinine level in the 1st course deteriorated during the course. T.Bil levels on the re-start day of this chemotherapy after 2-week intervals were especially high compared to that on the start day. The more courses of this chemotherapy we perform, the more attention we must pay to bone marrow suppression and hyperbilirubinemia. Thus, we clarified the attentive point of side effect of l-LV/5FU adjuvant chemotherapy for colorectal cancer.

BACKGROUND: Spheroid with hollow (SWH) induced by Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 (CEACAM1) and inner cells apoptosis is observed in three-dimensional (3D) in vitro culture and in an in vivo mouse model. However, it is unclear whether SWH exists in clinical cancer tissue. The aim of the current study is to address which cytoplasmic domain of CEACAM1 is responsible for SWH formation, and to elucidate the existence and the implication of SWH in colorectal cancer. METHODS: To address which cytoplasmic domain of CEACAM1 is responsible for SWH formation, 3D culture was conducted to investigate lumen formation of colorectal cancer cells (LS174T and HT29) transfected with CEACAM1-4L (long cytoplasmic isoform), -4S (short cytoplasmic isoform), or shRNA for CEACAM1. Immunohistochemical analyses were conducted with CEACAM1, CEACAM1-L (long cytoplasmic isoform) and M30 (cleaved cytokeratin 18 fragment) as an apoptosis marker on clinical samples from 164 patients with colorectal cancer. The risk factors for metastases and survival were calculated using univariate and multivariate analyses. RESULTS: In 3D culture experiment, CEACAM1-L is responsible for lumen formation of colorectal cancer cells. Knock down of CEACAM1 or over-expression of CEACAM1-4S inhibited lumen formation, indicating that modulation of CEACAM1 can control SWH structure. Immunohistochemical analyses showed that CEACAM1 expressing spheroid with hollow accompanying with central cells apoptosis shown by M30 staining existed at the invasion front of colorectal cancer tissues. All of SWH was stained by CEACAM1 and CEACAM1-L. It means that SWH at the invasion front has already acquired tumor initiating property. A multivariate analysis showed that the SWH is an independent risk factor for lymph node metastasis (p=0.004) and distant metastasis (p=0.002). The SWH was also identified to be an independent prognostic factor by a Cox proportional hazards model (p=0.020). The Kaplan-Meier evaluation for the overall survival analysis showed that SWH was significantly associated with a shorter survival (p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5234. doi:10.1158/1538-7445.AM2011-5234