Hisashi Onodera

Increased intratumor Valpha24-positive natural killer T cells: a prognostic factor for primary colorectal carcinomas.

Purpose: Human invariant natural killer T (NKT) cells are novel, distinct lymphocyte populations with a restricted T-cell receptor repertoire (Vα24-Vβ11). They play a pivotal role in immunoregulation and in antitumor activities. This study focused on Vα24+ NKT cells in colorectal carcinomas and their clinicopathologic significance. Experimental Design: Vα24+ NKT-cell infiltration immunohistochemistry was studied in a total of 103 colorectal carcinoma cases. The degree of NKT-cell infiltration in tumors was evaluated as low (<7 NKT cells/5 HPF) or high (≥7 NKT cells/5 HPF). The correlation between the degree of infiltrated Vα24+ NKT cells and clinicopathologic variables was studied statistically. Results: A small number of Vα24+ NKT cells were found in the normal colorectal mucosa (2.6 ± 3.7 cells/5 HPF); however, their number increased remarkably in colorectal carcinomas (15.2 ± 16.3 cells/5 HPF; P = 0.0003) and a majority showed phenotype of activation. Higher NKT-cell infiltration was more frequent in women than in men (P = 0.034) and correlated with fewer lymph node metastases (P = 0.042). Patients with high NKT-cell infiltration showed higher overall (P = 0.018) as well as disease-free (P = 0.0006) survival rates. Intratumor NKT-cell infiltration was an independent prognostic factor for the overall (P = 0.033) and disease-free (P = 0.0064) survival rates. Conclusions: Increased infiltration of Vα24+ NKT cells was observed in colorectal carcinomas. Higher Vα24+ NKT-cell infiltration in colorectal carcinomas was an independent prognostic factor for favorable prognosis.

Absence of Smooth Muscle Actin-Positive Pericyte Coverage of Tumor Vessels Correlates with Hematogenous Metastasis and Prognosis of Colorectal Cancer Patients

Objectives: Immature microvessels, which are not covered by pericytes, are irregular and leaky. We hypothesized that tumor cells can penetrate immature microvessels more easily than mature microvessels. In this study, we investigated the maturation of angiogenesis by the immunohistochemical staining of colorectal cancer specimens and determined the correlation between the microvessel count or the maturity of microvessels and clinicopathological variables. Methods: Ninety-two surgical specimens from our department were used. Double immunostaining of endothelial cells with anti-CD34 antibody and pericytes with anti-α-smooth muscle actin antibody was performed. The microvessel density (MVD) and microvessel pericyte coverage index (MPI) as an index of microvessel maturation were evaluated. Results: The MVD showed a significant positive correlation with tumor size, depth of invasion and Dukes’ stage. The MPI showed a significant positive correlation with the histological differentiation of the tumor tissues and distant metastasis at the time of operation. The high MVD group (≧26.0, n = 50) tended to have a poorer prognosis than the low MVD group (<26.0, n = 42) (p = 0.097). Next, the 50 patients in the high MVD group were classified into two subgroups of high MPI (≧78.1%, n = 25) and low MPI (<78.1%, n = 25). MPI showed a significant negative correlation with hematogenous metastasis, and the low MPI group demonstrated a significantly poorer survival than the high MPI group (p = 0.040). Conclusions: These findings demonstrate that immature neovascularization was observed in poorly differentiated tumors and was correlated with metastasis, resulting in a poorer prognosis. Taken together, not only microvessel density but also vascular maturation were crucial factors for colorectal cancer patients.

Tissue factor expression in human colorectal carcinoma

It has been suggested that tissue factor (TF) plays an important role in tumor metastasis. Its expression in sarcoma cells was reported to up‐regulate the vascular endothelial growth factor (VEGF) gene and thereby enhance tumor angiogenesis, which is essential to tumor metastasis. Although many malignant tumors have been reported to express this protein constitutively, recent clinical studies have focused mainly on the correlations among TF expression, tumor progression, and histologic grade. Therefore, to address the role of TF and the underlying mechanism of hematogenous metastasis of colorectal carcinoma, the authors analyzed the correlations among TF expression, hepatic metastasis, and VEGF gene expression in surgical specimens. Furthermore, they analyzed the prognostic significance of TF expression with respect to overall patient survival.

Correlation of Tensile Strength with Bursting Pressure in the Evaluation of Intestinal Anastomosis

Background: Although bursting pressure and tensile strength have long been measured to evaluate anastomotic techniques, it has yet to be clarified whether or not they are correlated, what implications they have, and which should be used as a gold standard. Material and Methods: Using an experimental model to estimate pressure and tension in the same colonic anastomosis, the following variables were measured in 48 rats between days 0 and 14: bursting pressure (BP); minimal tensile strength (MITS) necessary to break a part of the anastomosis, and maximal tensile strength (MATS) needed to disrupt the whole anastomosis. Also, circulatory wall tension (CWT) was derived from BP and the anastomotic circumference (AC), and longitudinal wall tension (LWT) from MITS and AC. These variables were compared using correlation and regression analysis. Results: During the lag phase (days ≤4) there was poor correlation between pressure-related and tension-related variables whereas highly significant correlations were noted in the subsequent fibroplastic phase (day ≥5). It was shown by regression lines that positive MITS and MATS were expected when BP was zero. Conclusion: Contrary to the previous assumption, no correlation was found between BP and tensile strength in the critical postoperative period. Based on our present and previous studies, measurement of MITS is recommended to evaluate the healing of colonic anastomosis.

Implication of vascular endothelial growth factor and p53 status for angiogenesis in noninvasive colorectal carcinoma

It still is unclear when angiogenic potential, which is believed to be a prerequisite for tumor development, is acquired. The current study was designed 1) to clarify when the phenotypic change of angiogenicity occurs during the development of colon carcinoma and 2) to investigate the possible roles of vascular endothelial growth factor (VEGF) and p53 in angiogenesis.

New Pancreas-preserving Total Duodenectomy Technique

Pancreas-preserving total duodenectomy (PPTD) was first described by Chung et al. in 1994. Since then, several surgeons have used PPTD to treat diseases that involve the duodenum diffusely but not the head of the pancreas, mostly familial adenomatous polyposis (FAP). The PPTD method has been changed in each report and seems to have improved over time. We performed PPTD on three patients with different diseases-one with intestinal hemorrhage due to small intestinal amyloidosis; another with numerous duodenal gastrinomas in a patient with multiple endocrine neoplasia type 1 (MEN-1) and Zollinger-Ellison syndrome (ZES); and the third with numerous duodenal polyposis and FAP-using a new method that is simpler and safer than those previously reported. When resecting the whole duodenum, we performed mucosectomy of the major papillar portion and saved the structure of the major papilla. After an approximately 8 mm long sphincteropapillotomy, the opened major papilla was anastomosed to an incisional opening of the small intestine. The orifice of the main pancreatic duct (MPD) was stented by a catheter, and the MPD was kept intact under direct vision during the operative procedures. The head of the pancreas was fixed with the small intestine by interrupted 4-0 silk sutures. Reconstruction of the alimentary tract was performed after either the Billroth I or the Billroth II method. This is the first report of PPTD in which the entire MPD was preserved to simplify the biliopancreatic-ductal reconstruction.

Expression of Insulin-Like Growth Factor-2 Can Predict the Prognosis of Human Colorectal Cancer Patients: Correlation with Tumor Progression, Proliferative Activity and Survival

Expression of insulin-like growth factor-2 (IGF-2) has been reported in tissue specimens and cell lines of human colorectal cancers. However, the effects of IGF-2 in colorectal cancer patients are not well known. In this study, IGF-2 staining was performed on tissue samples from 92 patients with colorectal cancer, and the relationship of IGF-2 staining to clinicopathological variables, proliferating cell nuclear antigen (PCNA) staining and patient survival was analyzed. IGF-2 staining was correlated with tumor progression, PCNA staining and patient survival. Our results suggest that IGF-2 plays an important role in tumor progression and that IGF-2 staining is useful as a prognostic factor in colorectal cancer patients.

Functional outcome, quality of life, and efficacy of probiotics in postoperative patients with colorectal cancer.

PurposeWe investigated the functional outcome and health-related quality of life (QOL) of patients who underwent a surgical resection of colorectal cancer, and reviewed the efficacy of probiotics for improving bowel function.MethodsA questionnaire was mailed to 193 patients. Questionnaires contained the Medical Outcomes Study Short-Form 36-Item Health Survey and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 as QOL scores, the Wexner incontinence score, and original questionnaire items about bowel functions. Probiotics, containing Bacillus natto and Lactobacillus acidophilus, were given to 77 patients for 3 months; after 3 months of treatment, the same questionnaire was administered. The results were analyzed by location of the resected cancer: rectal, colonic, right, and left.ResultsIn the rectal group, defecation frequency, anal pain, and the Wexner score were significantly worse than in the colonic group. In the right group, the fecal form was looser and nighttime defecation frequency was higher than those of the left group. Three items in the QOL score of the right group were significantly worse compared with the left group. Functional outcome including defecation frequency, feeling of incomplete defecation, and five items in the QOL score were significantly improved after taking probiotics. Improvement in functional outcome and/or QOL was observed in all groups.ConclusionsNot only rectal resection but also rightside colectomy affected bowel dysfunction. Probiotics could be an effective treatment for improvement in functional outcome and QOL after colorectal resection.

Reappraisal of Surgical Treatment for Radiation Enteritis

Although radiation enteritis is a well-recognized sequel of therapeutic irradiation, the standard surgical method is not universally agreed upon. Not only the short-term effect but also the long-term effect after a surgical intervention has been fairly well reported. To reassess the surgical therapy for radiation enteritis, we retrospectively analyzed 48 patients (5 males and 43 females, mean age 58.6 years) who had been operated on in our department. These patients were divided into two types according to the time of surgery or the clinical manifestation, and operative methods were analyzed. Patient’s status such as bowel movement, body weight, and serum albumin value after surgery were analyzed, together with the patients survival. Our surgical methods were small intestinal resection for the intestinal obstruction, and pull-through reconstruction for proctitis. Two patients died of multiple organ failure caused by perforated peritonitis irrespective of emergent operation. Although the overall morbidity was 21.7%, there was no leakage when bowels were anastomosed. Overall survival after radiation-related complication in patients without previous neoplastic disease recurrence was 89%, 79%, and 69%, at 1, 3, and 5 years after surgery, respectively. Bowel motility, serum albumin level, and body weight recovered gradually soon after the operation and reached satisfactory levels within 6 months. Our analysis showed that small bowel injury should be treated by generous resection of the affected bowel followed by careful anastomosis of the disease-free ends, while rectal resection is best dealt with by restorative proctectomy. This may provide a good quality of life and minimize major postoperative complications such as leakage.

Intramuscular metastasis from gastric cancer

Abstract.Skeletal muscle is an uncommon site of hematogenous metastasis of gastric carcinoma. We report here a rare case of gastric carcinoma with multiple intramuscular metastases. Our patient had advanced gastric carcinoma and complained of left gluteal induration with tenderness. Because magnetic resonance imaging (MRI) revealed that the gluteal tumor showed iso-signal intensity on T1-weighted images and high signal intensity on T2-weighted images, with reticulated texture around the tumor, and the patient had advanced gastric carcinoma, we speculated that the tumor was an intramuscular metastatic tumor from primary gastric carcinoma. There were also multiple intramuscular metastatic lesions in both gluteal muscles on the MRI findings that were not detected by physical examination. Therefore, the patient underwent total gastrectomy with combined resection of spleen, with subsequent chemotherapy. Three months after the operation, we excised the gluteal tumor to alleviate the gluteal pain. Histological examinations confirmed that the gluteal tumor was a metastasis from primary gastric carcinoma.