Prospective observational study comparing the perioperative outcomes of laparoscopic colectomy with or without epidural anesthesia: the Kanagawa Yokohama Colorectal Cancer Study Group (KYCC) 1806.

PURPOSE: There have been no adequate comparisons of the efficacy, safety, and efficiency of analgesia after laparoscopic colorectal resection (LAC), with and without epidural anesthesia (EDA). METHODS: This was a multicenter prospective observational study of patients undergoing LAC. The primary end point was the mean visual analog scale (VAS) score on postoperative days (PODs) 1-7. The secondary end points were the highest VAS, complication rate, days to first ambulation and fatigue, length of hospital stay, and time to commencement of surgery. RESULTS: We compared an EDA group (Group E, n = 48) and a no-EDA group (Group O, n = 48) after matching. The mean VAS was not significantly different between the groups (28.7 vs. 30.1, p = 0.288). On assessing the secondary end points, the highest VAS was not significantly different between the groups. In fact, the VAS was lower in Group E only on POD 2. There was no difference in the incidence of complications, the time to first postoperative evacuation was shorter in Group E, and postoperative hospitalization was similar. The time to surgery was shorter in Group O. CONCLUSION: These results suggest that LAC without EDA is a feasible option, but with the early and regular use of adjunctive measures to provide more stable analgesia.

[A Case of Overwhelming Post Splenectomy Infection(OPSI)after Operation for Sigmoid Colon Cancer].

A 64-year-old woman was diagnosed with hereditary spherocytosis 30 years ago and underwent splenectomy. She presented to the hospital with lower abdominal pain and was diagnosed with sigmoid colon cancer(cT3N3M1[LYM], H1, Stage Ⅳ)for which sigmoidectomy was performed. On the 7th postoperative day, a fever of 40℃ and an inflammatory reaction were observed. She developed a consciousness disorder the next day, and her condition rapidly deteriorated along with the development of septic shock and disseminated intravascular coagulation(DIC). With the aid of a ventilator, immediate treatment for DIC was started, but reversion of septic shock and DIC was not possible, and the patient died of multiple organ dysfunction on the 17th postoperative day. Computed tomography and urinalysis performed during the course of treatment showed no infected lesion, but Citrobacter spp. was detected thrice in venous blood culture. Hence, the patient was diagnosed as a case of Citrobacter overwhelming post splenectomy infection(OPSI). To our knowledge, this is the first report of Citrobacter spp. infection following an abrupt course of OPSI.

[A Case Survived Long Period after Repeated Operation against the Small Intestinal GIST with Perforation].

A patient was 60-year-old man. In March 2011, the small bowel tumor with perforation was found and the partial resection of small intestine was urgently performed. KIT of resected specimen was positive. Then, diagnosis as GIST was defined. Oral administration of imatinib was started, but it was finished in 5 months because of development of the systemic edema. In February 2013, the abdominal CT revealed a tumor of 20 cm in size in the pelvis. Upon laparotomy, we detected the GIST recurrence generated at the region of small intestine anastomosis where manipulated previously, then resected all of tumor and partially small intestine. Afterward, we diagnosed as a recurrence of GIST. In March 2014, the abdominal CT found 4 cm sized mesenteric tumor and 2 cm sized abdominal wall tumor. The laparotomy was performed and we found 5 disseminated nodules intraperitoneally. We confirmed that all of these disseminated nodules were successfully removed. We defined them as re-recurrence of GIST. Six years and 5 months have elapsed since the first operation was performed, but there is no sign of three times recurrence.

[Long-Term Survival after Resection for Repeated Abdominal Wall Recurrence of Gallbladder Cancer].

We report the case of a 79-year-old woman with repeated abdominal wall recurrence of gallbladder cancer. The original diagnosis was gallbladder carcinoma. She underwent open liver bed dissection and lymph node dissection. Postoperative pathological examination indicated T2N1M0, Stage III disease. She received 6 courses of postoperative chemotherapy with gemcitabine. Two years and 2 months after the surgery, we detected a 13 mm mass under the abdominal wall scar on CT, and we resected this tumor. Pathological findings indicated adenocarcinoma, which was found to be metastasis of the gallbladder cancer. She was treated with S-1 for 8 courses postoperatively. However, 3 years 4 months after the first surgery, a tumor of 22mm was detected in the abdominal wall on the caudal side away from the previous tumor excision site. We resected the abdominal wall including the tumor. The pathological examination revealed adenocarcinoma, which was again metastasis from gallbladder cancer. The increase of CA19-9 was confirmed around 4 years and 7months after the first operation. An abdominal wall tumor of 45mm was detected in contact with the iliac bone near the last excision site and it proved to be a recurrence of gallbladder carcinoma. We performed abdominal wall tumor resection, again identifying adenocarcinoma, which was the third recurrence of gallbladder cancer. Despite continued abdominal wall recurrence, she is alive and well without metastasis for more than 5 years.

The regulation of soluble receptor for AGEs contributes to carbonyl stress in schizophrenia.

Our previous study showed that enhanced carbonyl stress is closely related to schizophrenia. The endogenous secretory receptor for advanced glycation end-products (esRAGE) is a splice variant of the AGER gene and is one of the soluble forms of RAGE. esRAGE is considered to be a key molecule for alleviating the burden of carbonyl stress by entrapping advanced glycation end-products (AGEs). In the current study, we conducted genetic association analyses focusing on AGER, in which we compared 212 schizophrenic patients to 214 control subjects. We also compared esRAGE levels among a subgroup of 104 patients and 89 controls and further carried out measurements of total circulating soluble RAGE (sRAGE) in 25 patients and 49 healthy subjects. Although the genetic association study yielded inconclusive results, multiple regression analysis indicated that a specific haplotype composed of rs17846798, rs2071288, and a 63 bp deletion, which were in perfect linkage disequilibrium (r2 = 1), and rs2070600 (Gly82Ser) were significantly associated with a marked decrease in serum esRAGE levels. Furthermore, compared to healthy subjects, schizophrenia showed significantly lower esRAGE (p = 0.007) and sRAGE (p = 0.03) levels, respectively. This is the first study to show that serum esRAGE levels are regulated by a newly identified specific haplotype in AGER and that a subpopulation of schizophrenic patients are more vulnerable to carbonyl stress.

[A Case of Stage IV Gastric Cancer Successfully Treated Using Salvage Surgery after S-1/CDDP Therapy].

A 75-year-old man admitted for left lateral abdominal pain was found to have advanced poorly differentiated gastric adenocarcinoma with abdominal para-aortic and Virchow's lymph node metastases, which was diagnosed to be clinical Stage IV (T3N3H0M1[LYM]). As curative surgery was not deemed possible, we started chemotherapy administration using S-1 (120mg/day)administered orally for 3 weeks and cisplatin(CDDP 100mg/body)administered intravenously on day 8. After 6 courses of chemotherapy, a CT scan showed that all lymph nodes metastases had disappeared, resulting in downstaging to clinical Stage II (T3[SE]N0H0P0M0). Thus, we performed total gastrectomy, lymph node dissection(D2), and splenectomy. Histological findings showed no residual tumor cells in any of the lymph nodes. However, cancer cells remained in the primary gastric lesion. The pathological response to chemotherapy was judged to be Grade 2. The patient has been recurrence-free for 5 years after surgery.

cAMP ameliorates inflammation by modulation of macrophage receptor for advanced glycation end-products.

Clarification of the roles of PAMPs (pathogen-associated molecular patterns) and DAMPs (damage-associated molecular patterns) is indispensable for therapeutic strategies against various inflammatory diseases. RAGE (receptor for advanced glycation end-products) is one of the PRRs (pattern recognition receptors) and has been implicated in autoimmune and inflammatory diseases. Effective remedies targeting RAGE are required for the diseases. In the present study, we show that cAMP-induced modulation of the RAGE isoform in macrophages can control the inflammatory state in both in vitro and in vivo experimental conditions. The RAGE ligand S100B stimulated MCP-1 (monocyte chemoattractant protein-1) secretion from peritoneal macrophages, but cAMP elevation suppressed it by converting the RAGE isoform from a membrane-bound into a soluble form. This shedding is the result of ectodomain cleavage of mRAGE (membrane-bound RAGE) by MMP9 (matrix metalloproteinase 9). Furthermore, forskolin significantly inhibited peritoneal macrophage accumulation in a mouse S100B-induced peritonitis model. These results suggest that cAMP serves as a negative regulator of ligand-RAGE signalling and macrophage recruitment by mRAGE down-regulation and formation of decoys as soluble receptors. The present study should deepen our understanding of the pathogenesis of RAGE-mediated tissue derangement and provide new clues for overcoming RAGE-related inflammatory diseases.

[Experience of the Pharmacotherapy against Appendix and Sigmoid Colon Signet Ring Cell Carcinoma with the Peritoneal Dissemination].

We report 2 cases of signet ring cell carcinoma of the appendix and colon. Case 1: A 61-year-old man was admitted for lower abdominal pain. Colonoscopy revealed an elevated lesion in the orifice of the appendix. Signet ring cell carcinoma was diagnosed on biopsy. The surgical findings showed multiple peritoneal dissemination nodules, while the primary tumor was unresectable owing to extensive invasion into the retroperitoneum. The histopathological findings were signet ring cell carcinoma, T4b (retroperitoneum), NX, P3, Stage Ⅳ. Although the patient received 14 courses of treatment with S-1 as postoperative chemotherapy, he died of his illness at 32 postoperative months. Case 2: A 76-year-old man was admitted for abdominal pain. Perforation of the lower gastrointestinal tract was diagnosed on abdominal CT, and an emergency operation was performed. The surgical findings demonstrated a large number of peritoneal dissemination nodules, cecal invasion of a sigmoid tumor, and perforation of the ascending colon. The primary tumor was thought to be unresectable, and the perforated segment was resected. The histopathological findings were signet ring cell carcinoma, T4b (cecum), NX, P3, Stage Ⅳ. Although 11 courses of treatment using FOLFIRI+Bev were administered as postoperative chemotherapy, the patient died of his illness at 26 postoperative months.

[Clinicopathological Features and Outcomes of Treatment for HER2 Positive Gastric Cancer].

In March 2011, trastuzumab was approved for treating human epidermal growth factor receptor 2 (HER2) positive advanced gastric cancer (AGC) in Japan. Therefore, all patients with AGC should be evaluated for HER2 status. In this study, we analyzed the clinicopathological features and current status of treatment in HER2 positive gastric cancer. One hundred 6 gastric cancer patients were examined for HER2 expression in our hospital between March 2011 and August 2014. Sixteen patients (15.1%) were HER2 positive. There was no correlation between HER2 status and age, sex, and location of tumor; however, HER2 positivity was significantly more frequent in patients with intestinal type tumors and had a tendency towards being more frequent in patients with macroscopic types 0, 1 or 2. Trastuzumab was administered to 10 patients with HER2 positive AGC. The total number of doses of trastuzumab was 1 to 44 (median 7.5), and the therapeutic effect of trastuzumab combination chemotherapy was 1 patient with a complete response and 4 with a partial response. Adverse events due to trastuzumab were not observed. The incidence of HER2 over-expression was 15.1%, and trastuzumab combination chemotherapy was relatively safe and effective.

[The Outcomes of Laparoscopy-Assisted Surgery in Elderly Patients with Colorectal Carcinoma].

AIM: To evaluate short-term outcomes of laparoscopy-assisted colectomy (LAC) in elderly patients with colorectal carcinoma. METHODS: A total of 289 colorectal cancer patients underwent LAC between 2008 and 2013. They were divided into an elderly group (<80 years of age, group E), and a younger group (<80 years of age, group Y). The treatment results, including the surgery-related factors, the perioperative course, and the pre- and postoperative complications, were retrospectively analyzed. RESULTS: There were 49 patients in group E, and 240 patients in group Y. There was no significant difference between the 2 groups considering the operative time, blood loss, rate of transfusion, post-operative hospital stay, rate of conversion to open surgery, or rate of complications, except for the number of patients with an ASA classification of greater than Grade 2 and the degree of lymph node dissection. CONCLUSIONS: LAC in elderly patients was found to be relatively safe because it was associated with a reduction in damage to the abdominal wall, and with an early recovery from surgery. These results suggest that the indications of LAC could be expanded for elderly patients.

Induction of receptor for advanced glycation end products by insufficient leptin action triggers pancreatic ß-cell failure in type 2 diabetes.

Glucolipotoxicity, which is exerted by free fatty acids (FFA) and prolonged hyperglycemia, is implicated in pancreatic ß-cell failure in diabetes. Pattern recognition receptors such as receptor for advanced glycation end products (RAGE) and toll-like receptors 2 and 4 could mediate danger signals in ß-cells. We examined whether RAGE contributes to ß-cell failure in a type 2 diabetes mouse model. Pancreatic islets were isolated from ob/ob, db/db, diet-induced obesity (DIO), RAGE-null (RAGE(-/-) ), and RAGE(+/+) wild-type (WT) control mice and dispersed into single cells for flow cytometry. RAGE expression was detected in insulin-positive ß-cells of ob/ob and db/db mice, but not of WT, DIO, or RAGE(-/-) mice: thus, inadequate leptin receptor signaling and RAGE expression may be linked. Compared with RAGE(+/+) db/db mice, RAGE(-/-) db/db mice showed higher ß-cell number and mass with less apoptosis as well as glucose tolerance with higher insulin secretion without any differences in serum levels of FFA and adiponectin. Palmitate or oleate pretreatment combined with a leptin antagonist induced RAGE expression, AGE-elicited apoptosis, and impaired glucose-stimulated insulin secretion by advanced glycation end products (AGE) in MIN6 cells. FFA elevation with concomitant AGE formation during prolonged hyperglycemia could cause ß-cell damage through insufficient leptin action and subsequent RAGE induction in type 2 diabetes.

[The role of staging laparoscopy in clinical stage III/IV gastric cancer].

We investigated the significance of staging laparoscopy (SL) for clinical Stage III/IVgastric cancer.SL was performed in 60 patients with clinical Stages III/IV gastric cancer.Pre -SL Stages were T3/4a/4b in 3/49/8 patients, N1/2/3 in 14/21/25, M0/ 1 in 38/22, and IIIA/IIIB/IIIC/IV in 16/13/9/22 patients, respectively.After SL, 11 patients were downstaged from T4a to T3, and 3 patients were downstaged from T4b to T4a.Moreover, 14 patients of P0 were identified as P1 or CY1, and 1 patient of H0 was identified as H1 after SL.As a result, post-SL Stages were IIB/IIIA/IIIB/IIIC/IV in 3/17/9/2/29 patients, respectively. In Stage III patients, staging was changed in 17 patients (44.7%) and the treatment strategies were changed in 9 patients (23.7%).In Stage IV cases, none of the patients changed staging and treatment strategies after SL.In conclusion, SL is useful for accurate staging and determining the treatment strategies in Stage III gastric cancer; however, re-evaluation is needed for the indication of SL in Stage IV gastric cancer.

[Clinical Impact of adjuvant chemotherapy in patients with T1N2/3 Gastric cancer].

The ACTS-GC trial showed the efficacy of S-1 adjuvant chemotherapy in patients with pathological Stage II/III gastric cancer who had undergone D2 gastrectomy; however, T1 patients were excluded from this trial.In this study, we compared the prognosis of T1N2/3 gastric cancer with the outcomes of ACTS-GC.From 2000 to 2009, out of 480 patients with resected T1 gastric cancer, 27 patients(5.6%) were pN2/3.Six patients received S-1 adjuvant chemotherapy (group S), whereas 21 patients did not(group N).The 3-year overall survival rates of T1N0/1 and T1N2/3 were 91.7% and 71.3%, respectively. Among T1N2/3 gastric cancer patients, the 3-year survival rate and relapse-free survival rate were 100%/100% in group S and 72.7%/71.1% in group N, respectively. The prognosis of group N was poorer than that of the surgery-alone group in Stage II of ACTS-GC.Furthermore, 5 patients (23.8%) of group N had recurrences; the primary sites of recurrences were lymph nodes in 4 cases, and lymph nodes and liver in 1 case.The prognosis of T1N2/3 gastric cancer is poor; we should, therefore, consider evaluating the efficacy of adjuvant chemotherapy in T1N2/3 gastric cancer patients.

[Outcomes of laparoscopic surgery after preoperative metallic stent placement for obstructive colorectal cancer].

AIM: To assess the outcomes of preoperative colonic stent placement for obstructive colorectal cancer. PATIENTS AND METHODS: A total of 30 patients with colorectal cancer were treated after preoperative colonic metallic stent placement between July 2012 and March 2014. We reviewed their medical records to assess the usefulness of stent placement and the clinical course. The effects of various clinicopathological variables on post-operative complications were analyzed statistically. RESULTS: Stent insertion was effective in 93% of the 30 patients with obstructive colorectal cancer. Preoperative colonoscopy or enema for proximal colonic survey was possible in 70% of the patients after stent placement; colonic lesions requiring simultaneous resection were noted in 5 patients (24%). The mean interval between stent insertion and operation was 19 days, and 23%of the patients underwent laparoscopic surgery. Statistical analysis revealed that the occurrence of complications was associated with laparoscopic surgery and the amount of operative blood loss. CONCLUSION: Preoperative stent placement in patients with obstructive colorectal cancer is feasible and laparoscopic surgery can be selected after stent placement.

Low molecular weight heparin suppresses receptor for advanced glycation end products-mediated expression of malignant phenotype in human fibrosarcoma cells.

The receptor for advanced glycation end products (RAGE) is a pattern-recognition receptor and its engagement by ligands such as high mobility group box 1 (HMGB1) is implicated in tumor growth and metastasis. Low molecular weight heparin (LMWH) has an antagonistic effect on the RAGE axis and is also reported to exert an antitumor effect beyond the known activity of anticoagulation. However, the link between the anti-RAGE and antitumor activities of LMWH has not yet to be fully elucidated. In this study, we investigated whether LMWH could inhibit tumor cell proliferation, invasion, and metastasis by blocking the RAGE axis using in vitro and in vivo assay systems. Stably transformed HT1080 human fibrosarcoma cell lines were obtained, including human full-length RAGE-overexpressing (HT1080(RAGE)), RAGE dominant-negative, intracellular tail-deleted RAGE-overexpressing (HT1080(dnRAGE)), and mock-transfected control (HT1080(mock)) cells. Confocal microscopy showed the expression of HMGB1 and RAGE in HT1080 cells. The LMWH significantly inhibited HMGB1-induced NFκB activation through RAGE using an NFκB-dependent luciferase reporter assay and the HT1080 cell lines. Overexpression of RAGE significantly accelerated, but dnRAGE expression attenuated HT1080 cell proliferation and invasion in vitro, along with similar effects on local tumor mass growth and lung metastasis in vivo. Treatment with LMWH significantly inhibited the migration, invasion, tumor formation, and lung metastasis of HT1080(RAGE) cells, but not of HT1080(mock) or HT1080(dnRAGE) cells. In conclusion, this study revealed that RAGE exacerbated the malignant phenotype of human fibrosarcoma cells, and that this exacerbation could be ameliorated by LMWH. It is suggested that LMWH has therapeutic potential in patients with certain types of malignant tumors.

Septic shock is associated with receptor for advanced glycation end products ligation of LPS.

Septic shock is a severe systemic response to bacterial infection. Receptor for advanced glycation end products (RAGE) plays a role in immune reactions to recognize specific molecular patterns as pathogen recognition receptors. However, the interaction between LPS, the bioactive component of bacterial cell walls, and RAGE is unclear. In this study, we found direct LPS binding to RAGE by a surface plasmon resonance assay, a plate competition assay, and flow cytometry. LPS increased TNF-α secretion from peritoneal macrophages and an NF-κB promoter-driven luciferase activity through RAGE. Blood neutrophils and monocytes expressed RAGE, and TLR2 was counterregulated in RAGE(-/-) mice. After LPS injection, RAGE(+/+) mice showed a higher mortality, higher serum levels of IL-6, TNF-α, high mobility group box 1, and endothelin-1, and severe lung and liver pathologies compared with RAGE(-/-) mice without significant differences in plasma LPS level. Administration of soluble RAGE significantly reduced the LPS-induced cytokine release and tissue damage and improved the LPS-induced lethality even in RAGE(-/-) as well as RAGE(+/+) mice. The results thus suggest that RAGE can associate with LPS and that RAGE system can regulate inflammatory responses. Soluble RAGE would be a therapeutic tool for LPS-induced septic shock.

[The clinical outcomes of endoscopic stent placement for patients with malignant gastric outlet obstruction - a comparison with gastrojejunostomy].

Owing to its less invasiveness, endoscopic stent placement is a potential treatment option for gastric cancer patients with gastric outlet obstruction( GOO). We compared the clinical outcomes of stent placement with gastrojejunostomy( GJ) bypass in terms of postoperative oral intake status, duration of oral intake, and overall survival. Thirty-eight patients who had unresectable gastric cancer with GOO were enrolled in this study. The stent placement group was divided into 2 subgroups: group P comprising 9 patients who received palliative treatment; and group A comprising 12 patients who received aggressive chemotherapy. Stent placement was performed for almost all the patients who had massive peritoneal metastasis and poor performance status. Improvement in oral intake was achieved in 19( 90.5%) of 21 patients after stent placement. Moreover, oral intake improved significantly in patients who underwent chemotherapy after stent placement. The median duration of oral intake and median overall survival was shorter in group P (1.8 and 2.8 months, respectively) and group A (3.2 and 4.8 months, respectively) than in group GJ( 11.8 and 12.7 months, respectively). In conclusion, endoscopic stent placement is effective in improving the oral intake status; however, it may be insufficient to improve the duration of oral intake. Thus, further studies are needed to clarify the clinical benefit of stent placement.

Characteristics of tumor thrombosis in the inferior mesenteric vein from colorectal cancer: A report of three cases and review of the literature.

INTRODUCTION: Intravenous tumor thrombosis is a rare condition in colorectal cancer and shows a locally aggressive biological behavior. We herein report three cases of colorectal cancer with tumor thrombosis in the inferior mesenteric vein (IMV) treated by colorectal resection combined with resection of the IMV under laparoscopic surgery. CASE PRESENTATION: In these three colorectal cancer patients with IMV tumor thrombus, IMV tumor thrombus was detected in all instances on preoperative computed tomography. Preoperative chemotherapy was also performed in one patient with concurrent liver metastasis. All patients underwent laparoscopic locally R0 resection; however, the pathological findings showed a positive margin for IMV resection in all patients. CLINICAL DISCUSSION: We reviewed 19 previously reported cases along with our 3 present cases and clarified the characteristics of colorectal cancer accompanied by IMV tumor thrombosis. IMV tumor thrombosis may be a risk factor for liver metastasis and R1 resection, and systemic treatment, including neoadjuvant chemotherapy (NAC), may be quite important. CONCLUSION: IMV tumor thrombosis may have a tendency to cause hematogenous metastasis. Systemic therapy, including NAC, may be useful, but since this is a rare condition, the accumulation of further cases is needed.

Immunohistochemical analysis of human equilibrative nucleoside transporter-1 (hENT1) predicts survival in resected pancreatic cancer patients treated with adjuvant gemcitabine monotherapy.

BACKGROUND: Gemcitabine is a promising adjuvant treatment for patients with resected pancreatic cancer. Human equilibrative nucleoside transporter-1 (hENT1) is the major transporter responsible for gemcitabine uptake into cells. The aim of this study was to retrospectively determine the relationship between the outcome of pancreatic cancer after surgery followed by postoperative gemcitabine monotherapy and the expression of hENT1. METHODS: A total of 27 resected pancreatic cancer patients treated with adjuvant gemcitabine were analyzed for tumor hENT1 expression via an immunohistochemical analysis. The staining intensity and the percentage of positive tumor cells were scored, and the composite score (hENT1 score) was obtained by obtaining the sum of these two scores. RESULTS: There were 11 patients assigned to the low hENT1 expression group, and 16 patients to the high hENT1 group. The patients with tumors that had higher hENT1 expression had a significantly longer disease-free survival (DFS) (log rank, P = 0.022) and overall survival (OS) (P = 0.024). The hENT1 expression was indicated to be a significant and independent prognostic factor for OS by the univariate (P = 0.030) and multivariate analyses (P = 0.019). CONCLUSIONS: A high expression of hENT1 in pancreatic cancer was found to be significantly associated with a longer survival in patients who received adjuvant gemcitabine monotherapy after curative resection, and hENT1 immunohistochemistry may well serve as a significant prognostic factor for these patients.

The clinicopathological features of colorectal mucinous adenocarcinoma and a therapeutic strategy for the disease.

BACKGROUND: The guidelines established by the National Comprehensive Cancer Network do not describe mucinous histology as a clinical factor that should influence the therapeutic algorithm. However, previous studies show conflicting results regarding the prognosis of colorectal mucinous adenocarcinoma. In this study, we described the clinicopathological features of mucinous adenocarcinoma in Japan, to identify optimal therapeutic strategies. METHODS: 144 patients with mucinous and 2673 with non-mucinous adenocarcinomas who underwent primary resection in two major centers in Yokohama, Japan were retrospectively evaluated for clinicopathological features and treatment factors. A multivariate analysis for overall survival followed by the comparison of overall survival using Cox proportional hazard model were performed. RESULTS: Patients with mucinous adenocarcinoma had larger primary lesions, higher preoperative CEA levels, a deeper depth of invasion, higher rates of nodal and distant metastasis, and more metastatic sites. A multivariate analysis for overall survival revealed a mucinous histology to be an independent prognostic factor. In the subgroup analysis stratified by stage, Patients diagnosed as stageIII and IV disease had a worse survival in mucinous adenocarcinoma than non-mucinous, while survival did not differ significantly in patients diagnosed as Stage0-II disease. In stageIII, local recurrence in rectal cases and peritoneal dissemination were more frequently observed in patients with a mucinous histology. CONCLUSIONS: Our study indentified that mucinous adenocarcinoma was associated with a worse survival compared with non-mucinous in patients with stageIII and IV disease. In rectal StageIII disease with mucinous histology, additional therapy to control local recurrence followed by surgical resection may be a strategical alternative. Further molecular investigations considering genetic features of mucinous histology will lead to drug development and better management of peritoneal metastasis.