Nobuhiro Tokunaga

Detection of tumor cells in the portal and peripheral blood of patients with colorectal carcinoma using competitive reverse transcriptase-polymerase chain reaction

In spite of many reports, it remains unclear whether the presence of tumor cells in circulating blood flow predicts a poor prognosis.

Small cell neuroendocrine carcinoma of the rectum

Poorly differentiated small cell neuroendocrine (NE) carcinoma of the colon and rectum is a rare primaty epithelial malignancy at this location. A case of a highly aggressive NE tumor of small cell type, combined with non‐invasive well‐differentiated papillary adenocarcinoma in villous adenoma is reported. The patient died rapidly with massive and progressive liver metastasis. The tumor cells were argyrophilic and diffusely immunoreactive for neuron‐specific enolase and synaptophysin. Ultrastructural analysis disclosed NE‐type cored granules in most of the small tumor cells. NE tumors of the colon and rectum are briefly reviewed.

Immunohistochemical localization of carcinoembryonic antigen as a predictor of lymph node status in submucosa-invasive colorectal carcinoma

PURPOSE: Submucosa-invasive colorectal carcinoma is a colorectal carcinoma extending only into the submucosal layer. To clarify the metastatic potential of submucosa-invasive colorectal carcinoma, we studied the relationship between the immunohistochemical staining pattern of carcinoembryonic antigen (CEA) and that of lymphatic invasion/ lymph node metastasis. METHODS: We investigated 49 submucosa-invasive colorectal carcinomas resected surgically or endoscopically. CEA distribution patterns of the neoplastic tissues were divided into three patterns: Pattern 1 = luminal type; Pattern 2 = apical cytoplasmic type; and Pattern 3 = diffuse cytoplasmic type. We also observed the submucosal stromal staining of CEA. RESULTS: Lymphatic invasion and lymph node metastasis were found in 48.8 percent (21/43) and 11.6 percent (5/43) of the Pattern 2/Pattern 3 cases, whereas these were seen in none (0/6) of Pattern 1 cases. Lymphatic invasion and lymph node metastasis were found in 63.3 percent (19/30) (chi-squared =21.94;P<0.001) and 16.7 percent (5/30) of the positive stromal CEA cases, whereas these were seen in 10.5 percent (2/19) and none (0/14) of the negative stromal CEA cases, respectively. CONCLUSION: Pattern 2/Pattern 3 and stromal CEA can be predictors of the lymph node metastasis with 11.6 percent and 16.7 percent risks.

A new method of evaluating hemorrhoids with the retroflexed fiberoptic colonoscope

BACKGROUND The conventional classification of the degree of hemorrhoids does not consider the severity of hemorrhage. The purpose of this study was to establish a new objective method for evaluating hemorrhoids in close relation to the main symptoms, hemorrhage and prolapse, as observed through a retroflexed colonoscope in the rectum. METHODS The subjects were 531 consecutive patients who complained of symptoms related to the rectum or the anus. The degree of mucosal elevation of the rectal columns, changes in color (the existence and degree of red color sign, dilated vein, and white area), and the existence and size of hypertrophied anal papillae were evaluated by colonoscopy. RESULTS Red color sign was the finding closely related to hemorrhage (p < 0.0001). Dilated vein, white area, and a large hypertrophied anal papilla were related to prolapse (p < 0.0001). The degree of mucosal elevation of the rectal columns was related to both hemorrhage and prolapse (p < 0.0005, p < 0.05). CONCLUSION Retroflexing the colonoscope intrarectally facilitated identification of findings in the anal canal related to hemorrhage and prolapse, which are the clinical manifestations of hemorrhoids.

Endoscopic balloon dilation for obstructive colorectal cancer: a basic study on morphologic and pathologic features associated with perforation

BACKGROUND The use of endoscopic dilation and a self-expandable stent for colorectal cancer (CRC) presenting with a stricture or obstruction, either prior to surgery or as a palliative measure (an alternative to colostomy), causes perforation with relative high incidence (1%-17%). OBJECTIVE To experimentally investigate risk factors associated with perforation in excised CRC specimens. DESIGN Experimental study. SETTING Ex vivo experiment on freshly excised human colon cancer specimens at an academic hospital. PATIENTS This study involved 47 patients with strictured CRCs of <15 mm in internal diameter as assessed by a preoperative contrast enema. INTERVENTION Immediately after surgical resection, a balloon with a diameter of 18 mm was placed in the stricture. The balloon was inflated slowly with hydrostatic pressure over 1 minute and kept at the maximum diameter for 1 minute. MAIN OUTCOME MEASUREMENTS Correlations between macroscopic perforation and 20 items, including morphological and histopathological characteristics. RESULTS Perforation occurred in 8 of 47 (17.0%) CRC specimens. Four items showed statistically significant (P < .05) correlations with perforation: peritumoral proliferation of collagen fibers (relative area > or =23.9% in the visual field), annularity of the tumor, severe stricture (<7.9 mm), and fewer residual smooth muscle cells in the muscularis propria, reflecting tumor encroachment. The best predictor of perforation was a combination of severe stricture and pronounced peritumoral proliferation of collagen fibers. LIMITATIONS An uncontrolled study with a small number of patients. CONCLUSION Histopathological and morphological items associated with a decrease in elastic compliance were more important as predictors of perforation than dilation procedure parameters, such as balloon pressure.

Development of an irradiation method of intraoperative radiation therapy for curatively resected rectal cancer

AbstractBackground. Intraoperative radiation therapy (IORT) has been performed to prevent local recurrence of rectal cancer only when positive margins are suspected. To further reduce local recurrence, we attempted to develop a new IORT irradiation method in which electron beam irradiation is administered as uniformly as possible to the intrapelvic dissection surfaces. Methods. Low anterior resection and abdominoperineal resection were performed in one male and one female cadaver. Electron beam irradiation was administered by four different methods, and absorbed doses were measured at 15 sites within the pelvis. We also attempted to measure absorbed doses at nine sites within the pelvis in 14 patients treated with IORT. Results. The cadaver study revealed low absorbed doses in the lateral walls of the pelvis when a single irradiation was delivered from the anterior. When the lateral walls of the pelvis were irradiated twice, once each time on the right and left, the absorbed doses were low in the central pelvis and presacrum. Relatively high absorbed doses were achieved in all of these areas by a technique that combined these two methods. Adequate absorbed doses were not achieved by a single irradiation administered from the perineum. Conclusion. This study suggests that electron beam irradiation administered three times to the dissected surfaces in the pelvis after resection of rectal cancer (i.e., to the central pelvis and presacrum from the anterior, and to the left and right lateral walls of the pelvis) is the most suitable method for achieving adequate absorbed doses.

Peritoneal Recurrence of Colon Cancer Detected by Positron Emission Tomography: Report of a Case

Increased glucose metabolism has been reported to occur in association with colorectal cancer. As positron emission tomography (PET) using [18F]fluorodeoxyglucose is able to depict hypermetabolic sites, it can therefore be used to detect colorectal cancer. A 69-year-old male patient with a recurrent solitary liver metastasis from colon cancer underwent whole-body PET which revealed high [18F]fluorodeoxyglucose uptake in the lesion. Furthermore, PET revealed peritoneal metastases that had not been detected by conventional imaging methods. Consequently, PET proved useful in helping us to avoid performing unnecessary treatment for the liver metastasis. Although it is uncertain whether early identification of recurrence can prolong survival, it may help to prevent unnecessary treatments being carried out. Thus, the application of PET in carefully selected patients could be beneficial to the management of recurrent colorectal cancer.

Preliminary study on the optimal dosage schedule for oral tegafur/uracil (UFT) chemotherapy

BackgroundWe evaluated a new dose-intensive schedule for oral UFT (tegafur and uracil in a molar ratio of 1:4) administered for 5 consecutive days followed by 2 drug-free days (weekly-5-method), in comparison with conventional daily administration (weekly-7 method), in Yoshida-sarcoma-bearing rats.MethodsThe single dose of 20 mg/kg of UFT for rats corresponds to the human single dose when converted to dose per unit of body-surface area. The drug was administered 3 times a day for the weekly-5 method and twice a day for the weekly-7 method. A 7-day period was considered 1 course. The total doses per course were almost the same in both methods. Antitumor efficacy and survival effect were evaluated after 3 courses. Body weight changes and food consumption were also measured as indices of toxicity. The plasma pharmacokinetics were analyzed by simulating dosage patterns.ResultsSignificant tumor-growth inhibition was seen with both the weekly-5 and the weekly-7 methods as compared to the control. Moreover, the weekly-5 method showed higher tumor-growth inhibition and a better survival effect than the weekly-7 method. These results appear to be related to the duration of plasma concentrations of 5-FU being maintained above a certain concentration for a longer time with the weekly-5 method. Food consumption with the weekly-5 method recovered to the control level after the drug-free period, and body weight gain was also favorable.ConclusionThe results of this study suggest that the dose-intensive method of administering UFT orally for the weekly-5 method is a useful dosage schedule. Thus, this dosage schedule is recommended for use in clinical trials.

Clinical Experiences with Laparoscopic Colectomy

Abstract: The indications for laparoscopic colon resection and the associated complications are discussed herein. This procedure was indicated for patients with benign disease or malignant disease with invasion limited to the submucosal layer. The subjects consisted of 14 cases with submucosal tumor invasion diagnosed preoperative, three with submucosal invasion clarified by endoscopic polypectomy, three with adenomas larger than 2 cm in diameter strongly suspected of being focal submucosal tumor invasion considered unsuitable for endoscopic mucosal resection and one with Crohns disease with ileus. Two cases in whom laparoscopic surgery was not appropriate were included in this series. In one case with a superficial elevated lesion (Ma type), 15 mm in diameter, a diagnosis of moderately differentiated adenocarcinoma of the cecum was made preoperatively, but subserosal tumor invasion of the colonic wall with negative lymph node metastasis (nO) was revealed by examination of the resected specimen. The histology of the second superficial elevated lesion (Ha+lie type), which had a central depression, 13 mm in diameter and located above Bauhins valve, was a well differentiated adenocarcinoma of which the cancerous portion invaded the proper muscle with positive lymph node metastasis (n1). Complications occurred in four cases. There were two cases of intraoperative vascular injury necessitating conversion to a standard laparotomy. One case with complete transection of the left ureter by End‐GIA later underwent reoperation. The other case with minor leakage at the anastomotic site was managed with conservative therapy. In both of these cases the depth of tumor invasion had been incorrectly assessed as representing small elevated lesions, 15 mm in diameter, in the right colon. Furthermore, the cases who experienced complications had left colonic lesions. These results suggest that preoperative ultrasonic‐endoscopy should be conducted as extensively as possible and that a good bloodless visual field appears to be necessary to avoid injuring adjacent organs.

Recurrence after Curative Resection of Submucosal Invasive Colorectal Carcinoma.

過去10年間の大腸sm癌外科切除104例の中で, 6例(5.8%)に術後転移再発を認めた. 局所・リンパ節再発は4例で, 直腸3例, 下行結腸1例であった. 組織型は中分化腺癌が3例, 高分化腺癌が1例で, 4例中3例はリンパ節転移陽性, 全例リンパ管侵襲陽性であり, 壁深達度細分類ではsm3であった. 3例に再切除を行い, 2例生存中である. 肝再発は2例で, 横行結腸1例, 上行結腸1例であった. 2例とも単発肝再発であり, 血中CEA値の上昇で, 肝再発を指摘しえ, 肝部分切除後無再発生存中である. 大腸sm癌の初回手術時の病理所見で中分化腺癌, リンパ節転移陽性例, リンパ管侵襲陽性例は, 局所・リンパ節再発のhigh risk groupとして, より入念な経過観察が必要である. 肝再発の予測は困難であるが, 肝転移を念頭においた術後の経過観察が重要であると思われた.