Postoperative Survival in Colitis-associated Colorectal Cancer With Ulcerative Colitis in Japan: A Multicenter Analysis.

BACKGROUND/AIM: The aim of the study was to analyze the postoperative survival of colitis-associated colorectal cancer (CAC) with ulcerative colitis (UC), and the risk factors affecting it. PATIENTS AND METHODS: A questionnaire including postoperative survival was sent to 88 hospitals that reported CAC patients in the literature up until January, 2006 and to members of the Research Group of Intractable Inflammatory Bowel Disease. RESULTS: The 5-year postoperative overall survival (OS) of 170 CAC patients was 74.2% which was similar to sporadic colorectal cancer in Japan (72.1%). Pathologic TNM stage, histological type, type of surgical procedure (proctocolectomy, segmental resection), and preoperative cancer surveillance were statistically significant factors for OS. By Cox regression analysis, pathologic TNM stage and proctocolectomy were statistically significant prognostic factors for OS. CONCLUSION: In CAC with UC, the postoperative OS was similar to sporadic colorectal cancer. Pathologic TNM stage and proctocolectomy were confirmed as important prognostic factors.

Clinical benefit of surgery for stage IV colorectal cancer with synchronous peritoneal metastasis.

BACKGROUND: Peritoneal metastasis is well-known as a poor prognostic factor in patients with colorectal cancer. It is important to improve the prognosis of patients with colorectal cancer and synchronous peritoneal metastasis. This study aimed to clarify the factors affecting R0 resection and the prognosis of colorectal cancer patients with synchronous peritoneal metastasis. METHODS: We investigated the data of patients with stage IV colorectal cancer between 1991 and 2007 in 16 hospitals that were members of the Japanese Society for Cancer of the Colon and Rectum. RESULTS: Of the 564 colorectal cancer patients with synchronous peritoneal metastases, 341 also had hematogenous metastases. The 5-year overall survival rates in patients with and without R0 resection were 32.4 and 4.7 %, respectively. A Cox proportional hazards model showed that histologic type of poorly differentiated adenocarcinoma, regional lymph node metastasis, liver metastasis, chemotherapy after surgery, R0 resection, the Japanese classification of peritoneal metastasis, and the size of peritoneal metastases were independent prognostic factors. Of the 564 patients, 28.4 % had R0 resection. The Japanese classification of peritoneal metastasis (P1-P2, p = 0.0024) and absence of hematogenous metastases (p < 0.0001) were associated with R0 resection. CONCLUSIONS: P1-P2 peritoneal metastasis and the absence of hematogenous metastasis were the most favorable factors benefiting from synchronous resection of peritoneal metastasis. In addition, chemotherapy after surgery was essential.

Risk factors for surgical site infection in Japanese patients with ulcerative colitis: a multicenter prospective study.

PURPOSE: A prospective, multicenter, observational study was performed to investigate the risk factors of surgical site infection (SSI) in patients with ulcerative colitis (UC). METHODS: From 2009 to 2010, perioperative clinicopathological data were collected from patients who had undergone surgery for UC within the research period, for up to 6 consecutive months in 13 hospitals in Japan. The primary outcome was the development of SSI. RESULTS: A total of 195 patients with UC who underwent colorectal surgery were enrolled. SSI was diagnosed in 38 (19.5 %) patients, in the form of incisional infection in 23 (11.8 %), organ/space infection in 16 (8.2 %), and both in 1 (0.5 %). There were no significant risk factors associated with an increased risk of development of incisional SSI. An American Society of Anesthesiologists physical status of ≥ 3 was indicated as the only significant risk factor for organ/space SSI (P = 0.02) compared with other factors, such as a neutrophil count of >100 × 10(2)/mm(3), albumin level of <3.5 g/dl, perioperative packed red blood cell transfusion, fair or poor colonic cleanliness, and therapeutic use of antibiotics. CONCLUSION: Poor general physical status was the significant independent risk factor for organ/space SSI in patients with UC in Japan.

Histologic evaluation of intrahepatic micrometastases in patients treated with or without neoadjuvant chemotherapy for colorectal carcinoma liver metastasis.

In the present retrospective study, we tested the hypothesis that neoadjuvant chemotherapy (NAC) as a treatment for patients with colorectal carcinoma liver metastases (CRLM) may reduce intrahepatic micrometastases. The incidence and distribution of intrahepatic micrometastases were determined in specimens resected from 63 patients who underwent hepatectomy for CRLM (21 treated with NAC and 42 without). In addition, the therapeutic efficacy of NAC was evaluated histologically. Intrahepatic micrometastases were defined as microscopic lesions spatially separated from the gross tumor. The distance from these lesions to the border of the hepatic tumor was measured on histological specimens and the density of intrahepatic micrometastases (number of lesions/mm(2)) was determined in regions close to (<1 cm) the gross hepatic tumor. Of the 21 patients treated with NAC, 13 were identified as having a partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines; thus, the overall response rate was 62%. Histologic evaluation of the therapeutic efficacy of NAC was significantly associated with tumor response to NAC according to the RECIST guidelines (p=0.048). In all, 260 intrahepatic micrometastases were detected in 39 patients (62%). Intrahepatic micrometastases were less frequently detected in NAC-treated patients than in untreated patients (5/21 [24%] vs. 34/42 [81%], respectively; p<0.001). There were no significant differences in the distance and density of intrahepatic micrometastases between the two groups (p=0.313 and p=0.526, respectively). In conclusion, NAC reduces the incidence of intrahepatic micrometastases in patients with CRLM, but NAC has no significant effect on their distribution when intrahepatic micrometastases are present.

[A case of advanced rectal cancer resected successfully after preoperative XELOX chemotherapy].

A-35-year-old female visited our hospital complaining of lower abdominal pain and atypical genital bleeding. A detailed examination revealed a rectal cancer with metastasis to the right ovary. Invasions to the uterus and right ureter were also detected. Three courses of XELOX therapy were administered as neoadjuvant chemotherapy. A subsequent examination revealed a significantly smaller metastatic lesion, and we therefore performed a radical resection. The pathological examination revealed that all surgical margins were negative for malignancy. We determined that there was no residual cancer and evaluated the surgery as curability A. The patient was administered XELOX therapy as adjuvant chemotherapy a month after the operation. Three months after the operation, the patient has remained in good condition with no signs or symptoms of tumor recurrence.

Postoperative defecatory function of an ileal pouch-anal anastomosis after a restorative proctocolectomy for ulcerative colitis: evaluation using fecoflowmetry.

An ileal pouch is usually reconstructed as an alternative to a neorectum after a total proctocolectomy for ulcerative colitis (UC). However, the real defecatory function of an ileal pouch is uncertain. This study was designed to analyze the functional and clinical outcomes after a proctocolectomy and ileal pouch-anal anastomosis (IPAA) for UC using fecoflowmetry (FFM). Sixteen patients who underwent IPAA for UC between 1990 and 2005 were studied. They were evaluated by FFM, together with Kelly's clinical score (KCS), and anorectal manometric assessments were also performed. FFM showed that the fecoflow pattern (FFP) of 14 patients (87%) was the block type and of 2 patients (13%) was the segmental type. The clinical score and tolerance volume showed no improvement 1 year or more after IPAA. However, the value of the maximum fecal stream flow rate (Fmax) improved with time. FFM shows that the defecatory function improved after IPAA, and it may therefore contribute to a good long-term outcome after the surgery.

[A case of fungal pyogenic spondylitis with ulcerative colitis].

A 58-year-old man with refractory ulcerative colitis underwent subtotal colectomy 4 months after the diagnosis. He developed intense back pain and high fever 9 days after the operation. Findings of a CT scan and an MRI confirmed the diagnosis of pyogenic spondylitis, and Candida albicans was cultured from the biopsy specimen. His clinical condition gradually improved after receiving therapy with rest and antifungal agents. Physicians should be aware of the possibility of pyogenic spondylitis in patients with back pain is treated for ulcerative colitis.

Comparison of a colonic J-pouch and transverse coloplasty pouch in patients with rectal cancer after an ultralow anterior resection using fecoflowmetric profiles.

PURPOSE: Because the standard straight coloanal anastomosis for low rectal cancer tends to result in unfavorable outcomes in terms of defecatory function, colonic pouch reconstruction has therefore recently been adopted in many institutions. The colonic J-pouch (CJP)- and transverse coloplasty pouch (TCP)-anal anastomoses have been adopted worldwide. However, the comparative benefits and drawbacks of the two procedures are uncertain. This study was designed to analyze the functional and clinical outcomes after an ultralow anterior resection (ULAR) using the fecoflowmetry (FFM). METHODS: Between November 1996 and July 2005, 18 patients were studied retrospectively. They were evaluated by FFM, together with Kelly's clinical score (KCS), and anorectal manometric assessments were also performed. RESULTS: The KCS directly correlated to the maximum fecal stream flow rate (Fmax). In this study, postoperative patients with good KCS as well as a high value of Fmax were seen more in the patients with CJP than in those with TCP. CONCLUSION: From the viewpoint of FFM, the patients with CJP had a more favorable functional outcome than those with TCP. FFM provided quantitative and qualitative evaluations concerning the anorectal motor activity in patients who had undergone an ULAR for rectal cancer.

[A long-term survival case of far-advanced colon cancer with Virchow's lymph node and lung metastasis that responded to multidisciplinary therapy].

The patient was a 73-year-old male. Under a diagnosis of advanced cecal colon cancer with metastasis to Virchow's and paraaortic lymph nodes and lungs, a laparoscopic-assisted ileocecal resection with D2 lymph node dissection was performed. Histological examination of the resected specimens revealed moderately-differentiated adenocarcinoma which had invaded the terminal ileum. The lesion was judged to be SI(ileum), N2, H0, P0, M1(Virchow's lymph node, No. 216, lungs), Stage IV. After the operation, he received chemotherapy with 5-FU/l-LV(RPMI method), LV/UFT, FOLFOX, FOLFIRI in succession, and cancer aggravation was generally controlled. He has survived for 3 years since operation, and shows good QOL under the treatment.

Potentiation of intestinal immunity by micellary mushroom extracts.

Mushroom (shiitake) extracts were dispersed with lecithin micelles to prepare superfine particles (0.05 to 0.2 microm in diameter) of beta-1,3-glucan (micellary mushroom extracts). When mice were fed with these micelles of beta-glucan (0.75 mg/day/mouse, smaller amounts of beta-glucan), the number of lymphocytes yielded by the small intestine increased by up to 40%. More interestingly, the ratio of CD8alphabeta(+)TCRalphabeta(+) cells/CD8alphaalpha(+)TCRalphabeta(+) cells increased prominently. In parallel with this deviation in the distribution of lymphocyte subsets, tumor cytotoxicity against P815 cells and cytokine productions were also augmented. In other words, phylogenetically developed lymphocytes (CD8alphabeta(+), TCRalphabeta(+)) were much more effectively activated by the oral administration of micellary beta-glucan. These results suggest that smaller amounts of micellary beta-glucan might be useful for the potentiation of intestinal immunity.

Common carotid arterial thrombosis associated with ulcerative colitis.

A 26-year-old woman with ulcerative colitis was transferred to our hospital with left hemiparesis due to cerebral infarction. Cervical ultrasonography and magnetic resonance imaging angiography revealed thrombosis at the right common carotid artery and the right internal carotid artery. Antithrombotic and anticoagulant therapies were commenced. After about 2 wk of the treatment, the frequency of her diarrhea increased. She underwent emergency subtotal colectomy, but 10 d later an abundant hemorrhage from the remnant rectum occurred, so the remnant rectum was resected and an ileal pouch anal anastomosis was performed. Antithrombotic and anticoagulant therapies were continued, but neither her neurological status nor magnetic resonance imaging angiography findings showed subsequent changes. She was discharged 3 mon after operation. This is a rare case of common carotid arterial thrombosis occurring as a complication of ulcerative colitis, in which antithrombotic and anticoagulant therapies are considered to provoke a deterioration of the patient's bowel disease.

Possible role of human cytomegalovirus in pouchitis after proctocolectomy with ileal pouch-anal anastomosis in patients with ulcerative colitis.

AIM: To detect the presence of human cytomegalovirus (HCMV) proteins and genes on the ileal pouch of patients with ulcerative colitis who have undergone proctocolectomy with ileal pouch-anal anastomosis (IPAA). METHODS: Immunohistochemistry, polymerase chain reaction (PCR) and PCR sequencing methods were utilized to test the presence of HCMV in pouch specimens taken from 34 patients in 86 endoscopies. RESULTS: HCMV genes and proteins were detected in samples from 12 (35.2%) patients. The rate of detection was significant in the endoscopies from patients diagnosed with pouchitis (5 of 12, 41.6%), according to the Japanese classification of pouchitis, in comparison to patients with normal pouch (7 of 62, 11.2%; P = 0.021). In all patients with pouchitis in which the HCMV was detected, it was the first episode of pouchitis. The virus was not detected in previous biopsies taken in normal endoscopies of these patients. During the follow-up, HCMV was detected in one patient with recurrent pouchitis and in 3 patients whose pouchitis episodes improved but whose positive endoscopic findings persisted. CONCLUSION: HCMV can take part in the inflammatory process of the pouch in some patients with ulcerative colitis who have undergone proctocolectomy with IPAA.

Prognostic groups in colorectal carcinoma patients based on tumor cell proliferation and classification and regression tree (CART) survival analysis.

BACKGROUND: In this study, an alternative analytical method was used to model colorectal cancer (CRC) patients' long-term survival by assessing the prognostic value of the Ki-67 protein as a marker of tumor cell proliferation, and to illustrate the interaction between standard clinicopathologic variables and the proliferation marker in relation to their impact on survival. METHODS: A cohort of 106 surgically treated CRC patients was used for analysis. The expression of the cell-cycle-related Ki-67 protein in tumor samples was evaluated by immunohistochemistry. A score was assigned as the percentage of positive tumor cell staining, denoted as proliferation index (PI), and was used in a multivariate analysis using a recursive partitioning algorithm referred to as classification and regression tree (CART) to characterize the long-term survival after surgery. RESULTS: Of the covariates selected for their prognostic value, PI contributed most to the classification of survival status of patients. However, CART analysis selected the presence of distant metastasis as the best first split-up factor for predicting 5-year survival. CART then selected the following covariates for building up subgroups at risk for death: (1) PI; (2) pathological lymph node metastasis; (3) tumor size. Seven terminal subgroups were formed, with an overall misclassification rate of 16%. CONCLUSIONS: These analyses demonstrated that a Ki-67-protein-based tumor proliferation index appeared as an independent prognostic variable that was consistently applied by the CART algorithm to classify patients into groups with similar clinical features and survival.

Change in the bacterial flora of pouchitis.

BACKGROUND/AIMS: Pouchitis is the most frequent complication of ileal pouch-anal anastomosis for patients with ulcerative colitis. While the mechanism of pouchitis is still unknown, a role involving the bacterial flora is suspected. The aim of the present study is to investigate the association between pouchitis and change in the bacterial flora. METHODOLOGY: This study included 22 patients who underwent ileal pouch-anal anastomosis in our department to treat ulcerative colitis. The mean age was 46.2 years. The male-to-female ratio was 10:12. The mean interval between surgery and this study was 95.6 months. Collected feces was serially diluted 10-fold to 10-8 and each solution was cultured. We diagnosed pouchitis using the pouchitis disease activity index. RESULTS: Nine of the 22 patients were diagnosed as having pouchitis. In the obligate anaerobes, the numbers of Bacteroidaceae and Bifidobacterium were significantly lower in the pouchitis group (P<0.01 and P<0.001). In the facultative anaerobic bacteria, the number of Lactobacillus was significantly lower in the pouchitis group (P<0.05). CONCLUSIONS: The numbers of Bacteroidaceae, Bifidobacterium and Lactobacillus were significantly lower in the bacterial flora of the pouchitis group. Our findings suggest that there is an association between change in the bacterial flora and pouchitis.

Activation of CD1d-independent NK1.1+ T cells in the large intestine by Lactobacilli.

Among digestive organs, the liver and the large intestine are abundant in T cells expressing NK1.1. NK1.1+ T cells in the liver are mostly CD1d-dependent whereas those in the large intestine are CD1d-independent. In this study, we investigated the effects of Lactobacilli on NK1.1+ T cells in the digestive organs of mice. C57BL/6 mice were orally given a dietary supplement prepared from mixed cultures of eight strains of Lactobacilli. Oral administration of Lactobacilli to mice resulted in the selective expansion of NK1.1+ T cells in the large intestine. These colon NK1.1+ T cells activated by Lactobacilli were found to express IFN-gamma mRNA. The level of IFN-gamma in the serum was also elevated by the administration of Lactobacilli. Our results suggest that Lactobacilli selectively activate CD1d-independent NK1.1+ T cells in the large intestine to produce IFN-gamma and therefore modulate Th1 immune responses.

[Repeated administration of alpha-galactosyl ceramide attenuates of natural killer T cells].

alpha-Galactosyl ceramide (alpha-GalCer) is well known as a specific ligand which can activate natural killer T (NKT) cells. This drug potentially induces anti-tumor effect of NKT cells, and clinical trials for alpha-GalCer in cancer patients are ongoing in the world. The aim of this study is to investigate how repeated alpha-GalCer injection affects the activation of NKT cells in mice. The initial administration of alpha-GalCer triggered a rapid production of both IFN-gamma and IL-4 in NKT cells and induced subsequent apoptosis in the majority of those cells. Meanwhile, no increase in IFN-gamma production was observed after further injections, and NKT cells maintained the low level secretion of IL-4 since the first injection. After repeated alpha-GalCer administration, activation markers on NKT cells were down-regulated and autologous cytotoxicity against liver cells decreased, suggesting that repeated stimulation attenuates the response of NKT cells to the ligand. These data indicate that prudent discussion is required to determine the dosing interval of alpha-GalCer in clinical applications. A further study is needed for establishing effective methods of sustained NKT cell activation.