Kazuhiro Seike

Laser Doppler assessment of the influence of division at the root of the inferior mesenteric artery on anastomotic blood flow in rectosigmoid cancer surgery

AimsThe aim of this study is to evaluate the influence of dividing the inferior mesenteric artery (IMA) and preserving the left colic artery (LCA) on rectosigmoid cancer surgery.Patients and methodsColonic blood flow at the proximal site of the anastomosis was measured by laser Doppler flowmetry in 96 patients with cancer of the rectum and sigmoid colon while clamping IMA or LCA. Results were analyzed with patient characteristics and postoperative complications.ResultsBlood flow was significantly decreased by either IMA or LCA clamping, and its reduction rate was 38.5 ± 1.8%, ranged from 0 to 82.8%, or 16.4 ± 1.8%, ranged from 0 to 66.2%, respectively. For multivariate analyses, aging and male gender were predictive factors of high blood flow reduction by IMA clamping. The reduction rate was significantly correlated with aging in male patients, while no such correlation was observed in women. Aging correlation in men was more significant in ultralow anterior resection cases. Three elderly male patients received IMA high ligation among 19 patients who demonstrated more than 50% blood flow reduction by IMA clamping. Among these, two patients, those who underwent ultralow anterior resection, suffered severe anastomotic ischemia.ConclusionsColonic blood flow at the proximal site of the anastomosis was significantly decreased by either IMA or LCA clamping. Patients with high reduction by IMA clamping need intraoperative efforts to prevent anastomotic ischemia, particularly in elderly male patients who undergo ultralow anterior resection.

Preoperative natural killer cell activity as a prognostic factor for distant metastasis following surgery for colon cancer.

Background/Aims: To determine whether preoperative natural killer (NK) cell activity has any prognostic significance in colon cancer patients. Methods: The study population consisted of 140 patients with colon cancer. NK cell activity was determined within 2 weeks before surgery in 128 patients and at the time of diagnosis in the remaining 12 patients who either did not undergo surgery or who underwent palliative surgery only. Disease progression and postoperative prognosis were examined in relation to NK cell activity. Results: Decreases in NK cell activity did not necessarily correspond to tumor stage. In curatively operated stage I–III diseases, preoperative NK cell activity of 20% or less correlated with poor survival. Lower activity was also associated with metachronous distant metastases but not with local recurrences. In particular, more than half the stage III patients with attenuated NK cell activity developed metastases. Multivariate analysis indicated that attenuated NK cell activity was a significant parameter for predicting distant metastasis following curative surgery for colon cancer. Conclusion: Preoperative NK cell activity has a significant prognostic value in curatively operated colon cancer, particularly for the development of metachronous distant metastasis in stage III patients.

Denervation of the neorectum as a potential cause of defecatory disorder following low anterior resection for rectal cancer

PURPOSEThe aim of this study was to determine whether denervation of the sigmoid colon during low anterior resection contributes to the postoperative motility characteristics of the neorectum and to the defecatory function of patients.METHODSSixty-seven patients who underwent either low or ultralow anterior resection for rectal cancer were evaluated. In accordance with the length of denervated neorectum, each patient was assigned to either the short-denervation or long-denervation group, determined by whether the inferior mesenteric artery was divided. Colonic propagated contraction was then measured by means of intraluminal pressure monitoring. Transit time was calculated with orally administered radiopaque markers.RESULTSPropagated contraction down to the neorectum was significantly less common in the long-denervation group (14/36) than in the short group (12/15, P < 0.05), whereas spastic minor contraction at the neorectum was significantly more common in the long-denervation group (21/36) than the in short group (3/15, P < 0.05). Colonic transit time below the sigmoid colon was significantly longer in long group (6.4 hours) than in the short group (3.4 hours, P < 0.01). Although motility disorder of the neorectum was correlated with clinical defecatory malfunctions, including multiple evacuations, urgency, and soiling, no significant correlation was noted between the length of the denervated neorectum and the defecatory disorders.CONCLUSIONSMotility of the neorectum following low anterior resection appears degraded by intraoperative maneuvers that cause denervation of the remnant sigmoid colon. Motility disorder of the neorectum, but not the length of the denervated neorectum causing the disorder, correlates well with several defecatory malfunctions. This finding suggests that postoperative defecatory disorder as a result of low anterior resection is caused by many factors in addition to denervation of the neorectum.

Assessment of Rectal Aberrant Crypt Foci by Standard Chromoscopy and its Predictive Value for Colonic Advanced Neoplasms

BACKGROUND AND AIMS:Aberrant crypt foci (ACF) are thought to be preneoplastic lesions and are assessed by magnifying chromoscopy with methylene blue staining. The aim of this study was to evaluate the predictive value of rectal ACF recognized by conventional chromoscopy for colonic advanced neoplasms.METHODS:Total colonoscopy, involving rectal chromoscopy using indigo carmine with standard colonoscopies, was performed on 386 patients. Patients who showed no ACF were classified as Grade 0, and those who had 1–4, 5–9, and 10+ ACF were classified as Grades 1, 2, or 3, respectively. The correlation between ACF grading and the prevalence of colonic advanced neoplasm, any adenoma ≥1 cm in size and/or with villous or tubulovillous morphology, and/or with high-grade dysplasia or invasive cancer, was assessed.RESULTS:Sixty-three patients were classified as ACF Grade 0, 119 as Grade 1, 116 as Grade 2, and 88 as Grade 3. Colonic advanced neoplasm was observed in 4 patients (6.3%) for Grade 0, 43 (36.1%) for Grade 1, 61 (52.6%) for Grade 2, and 57 (64.8%) for Grade 3. As the ACF grade increased, the chance of a patient having a colonic advanced neoplasm increased. For multivariate analyses, compared with patients with Grade 0, those with Grades 1, 2, or 3 had a greater risk of colonic advanced neoplasm (odds ratio [OR] 9.18, 95% CI 3.08–27.33, OR 20.44, 95% CI 6.81–61.42, and OR 32.94, 95% CI 10.49–103.41, respectively).CONCLUSIONS:Chromoscopic assessment of rectal ACF by conventional techniques is useful for predicting colonic advanced neoplasms.

Natural killer cell activity and distant metastasis in rectal cancers treated surgically with and without neoadjuvant chemoradiotherapy.

BACKGROUND We investigated whether impaired preoperative natural killer (NK) cell activity correlates with asynchronous distant metastasis after curative surgery for rectal cancers. In addition, we examined if preoperative chemoradiotherapy for rectal cancers impairs NK cell activity and contributes to the induction of distant metastasis. STUDY DESIGN Preoperative NK cell activity was examined in 174 rectal cancer patients. All patients were enrolled in this study and followed until asynchronous distant metastasis occurred. RESULTS The mean NK activity in patients with stage IV disease (n = 20) was significantly lower than seen in other stages. There were no differences among stage I to stage III patients. In stage III patients, the cumulative distant metastasis-free rate after curative surgery was significantly lower in cases with NK activity of 25% or less than those with more than 25%. Preoperative chemoradiotherapy for stage I to III patients significantly impaired NK cell activity (n = 39), and the metastasis-positive ratio significantly increased among patients with stage II or stage III diseases (n = 30). Multivariate analysis indicated that dichotomized NK cell activity was a significant risk factor that is associated with distant metastasis as well as nodal involvement. CONCLUSIONS In primary rectal cancers, NK cell activity is not necessarily impaired in accordance with the disease progression. It is considered an important background factor for developing asynchronous distant metastases in stage III rectal cancers. Neoadjuvant chemoradiotherapy impaired NK cell activity in selected patients, suggesting the necessity of concurrent immunotherapy for better outcomes.

Detection of Epstein-Barr virus in gastric carcinoma cells and surrounding lymphocytes

AbstractBackground. Epstein-Barr virus (EBV), the etiological agent of infectious mononucleosis, has an important role in the oncogenesis of EBV-related malignant diseases. The association of EBV with gastric carcinoma cells has become well known recently, but there are only a few reports concerning its association with surrounding epithelia and infiltrating lymphocytes. In this study, we investigated the association of EBV with gastric carcinoma and surrounding cells. Methods. One hundred and two cases of gastric carcinoma were studied. The specimens were studied for the presence of the EBV genome by polymerase chain reaction (PCR), and then by in situ hybridization (ISH) technique to determine the localization of EBV. Results. Of 97 informative cases, EBV was detected in 21 cases (21.6%) by the PCR method. ISH studies showed that EBV RNA was expressed in 5 of the 97 cases (5.2%) and was localized to the nuclei of carcinoma cells. All these 5 lesions were found in male patients. In these 5 cases, 3 were diffuse type and 2 were intestinal type, and all cases arose in the proximal region of the stomach. EBV RNA was not detected in non-neoplastic epithelia, but it was detected in 24 of the 97 cases (24.7%) in small lymphocytes. Conclusion. EBV was detected in 5.2% of gastric carcinomas and in 24.7% of infiltrating lymphocytes by the ISH method. The high positive rate (21.6%) by the PCR method corresponds to the presence of the EBV genome in surrounding lymphocytes.

Thymidylate Synthase and Dihydropyrimidine Dehydrogenase are Related to Histological Effects of 5-Fluorouracil and Cisplatin Neoadjuvant Chemotherapy for Primary Gastric Cancer Patients

Thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and vascular endothelial growth factor (VEGF) are associated with the effect of 5-fluorouracil (5-FU) based adjuvant chemotherapy. However, very few studies have investigated the relationship between these factors and 5-FU neoadjuvant chemotherapy for primary gastric cancer patients. In this study, we studied the correlation between these markers and the histological chemotherapeutic effect in advanced gastric cancer with neoadjuvant chemotherapy. Methods: Sixty-two primary advanced gastric cancer patients were recruited into the study. One cycle of continuous infusion of 5-FU (300 mg/m2/day, 14 days) plus drip infusion of cisplatin (15 mg/m2/day, Day one and Day two) was performed as neoadjuvant chemotherapy. Histological chemotherapeutic responses of the resected specimens were classified into responders and nonresponders. TS, DPD, VEGF expressions both before and after neoadjuvant chemotherapy were examined immunohistochemically. Results: There was an association between the TS-low group and the responders (p < 0.05); the DPD-low group and the responders in both biopsy and surgical specimens (p < 0.01). A combination of the low-TS and low-DPD group was further associated with responders (p < 0.01). The immunoexpressions of biopsied and surgical specimens were significantly associated with each other. Conclusion: Neoadjuvant chemotherapy for primary gastric cancer with one cycle of 5-FU and cisplatin was associated with histological findings in patients with low baseline TS and DPD. This dual determination may predict for efficacy of neoadjuvant treatment with these drugs.

Advanced moderately differentiated neuroendocrine carcinoma of the rectum with favorable prognosis by postoperative chemoradiation

Rectal neuroendocrine carcinoma is rare with poor prognosis. We report herein a case of advanced moderately differentiated neuroendocrine carcinoma of the rectum with relatively favorable prognosis treated by postoperative adjuvant chemoradiation therapy. A 58-year-old Japanese female was referred and colonofiberscopy revealed an easy-bleeding irregular tumor in the lower rectum, which was pathologically diagnosed as a neuroendocrine carcinoma. Surgical treatment consisted of abdominoperineal resection and lymph node dissection. The tumor invaded deeply into perirectal tissues, and 9 of 11 lymph node metastases were observed. Immunohistochemically, chromogranin A showed diffuse and strong staining, and the MIB-1 labeling index was 18.3 ± 5.6, supporting the high proliferation of the tumor. Some nucleus of the tumor showed positive staining for p21/WAF1. A total dose of 46 Gy of radiotherapy was delivered with 800 mg of daily oral doxifluridine. At 5 years post-surgery, the patient demonstrated no clinical evidence of intrapelvic recurrence or distant metastases.

Mesenteric transection decreases expression of interstitial cells of Cajal in an experimental model

After anterior resection for rectal carcinoma patients often complain of defaecatory dysfunction. The aim of this study was to examine the number of interstitial cells of Cajal (ICCs) and ganglion cells in the distal colon partially denervated by mesenteric transection in a rat model.

Efficacy of surgery after successful chemotherapy for advanced gastric cancer

BackgroundWe evaluated the efficacy of surgical resection after successful chemotherapies in patients with advanced gastric cancer.MethodsEighteen surgical patients who had had successful chemotherapies were selected after a review of 218 case records.ResultsThe 18 patients were grouped by their pretreatment status: 8 patients with distant lymph node metastases (N4 group), 7 with a small amount of ascites (P group), and 3 with both factors (N4+P group). Good responses were achieved in all of the 11 patients with node metastases, including 4 patients with a complete response. Ascites in 7 of 10 patients disappeared. Two of 18 patients (11%) achieved curability A resections, while 8 patients (44%) achieved curability B and 8 (44%) achieved curability C resections. Pathologic complete responses were documented in 2 patients of the N4 group. The median survival time of the 18 patients was 14 months, with a 1-year survival rate of 61%. Six patients have survived more than 2 years, and 3 more than 5 years to date. The 8 N4-group patients who had surgery showed significantly better survival than 19 similar patients who had distant metastases and responded to chemotherapy but did not have surgery. A similar comparison of the P-group patients found no significant difference in survival associated with surgery.ConclusionsSurgery after chemotherapy might be beneficial for patients with distant lymph node metastases, but not effective for those with peritoneal dissemination.