Tetsuichiro Muto

Correlations between lymph node metastasis and depth of submucosal invasion in submucosal invasive colorectal carcinoma: a Japanese collaborative study.

BackgroundDepth of submucosal invasion (SM depth) in submucosal invasive colorectal carcinoma (SICC) is considered an important predictive factor for lymph node metastasis. However, no nationwide reports have clarified the relationship between SM depth and rate of lymph node metastasis. Our aim was to investigate the correlations between lymph node metastasis and SM depth in SICC.MethodsSM depth was measured for 865 SICCs that were surgically resected at six institutions throughout Japan. For pedunculated SICC, the level 2 line according to Haggitt’s classification was used as baseline and the SM depth was measured from this baseline to the deepest portion in the submucosa. When the deepest portion of invasion was limited to above the baseline, the case was defined as a head invasion. For nonpedunculated SICC, when the muscularis mucosae could be identified, the muscularis mucosae was used as baseline and the vertical distance from this line to the deepest portion of invasion represented SM depth. When the muscularis mucosae could not be identified due to carcinomatous invasion, the superficial aspect of the SICC was used as baseline, and the vertical distance from this line to the deepest portion was determined.ResultsFor pedunculated SICC, rate of lymph node metastasis was 0% in head invasion cases and stalk invasion cases with SM depth <3000 µm if lymphatic invasion was negative. For nonpedunculated SICC, rate of lymph node metastasis was also 0% if SM depth was <1000 µm.ConclusionsThese results clarified rates of lymph node metastasis in SICC according to SM depth, and may contribute to defining therapeutic strategies for SICC.

Analysis of small cystic lesions of the pancreas

SummaryThere have been few reports on (1) the nature and pathogenesis of small cystic lesions of the pancreas, (2) their incidence, age distribution, and location, and (3) their significance as potential precursors of intraductal papillary tumors, mucinous cystic tumors, and duct cell carcinomas. Materials: Epithelial growth of small cystic lesions in 300 consecutive autopsy cases and in seven cases of small duct cell carcinoma from among 2300 elderly autopsy cases, was evaluated by histopathological analysis. One hundred eighty-six cystic lesions were found in 73 of 300 autopsy cases (24.3%). The incidence of cystic lesions increased with age. Cystic lesions were equally distributed throughout the pancreas. Epithelial atypia was histologically classified into five groups: normal epithelium; papillary hyperplasia without atypia; atypical hyperplasia; carcinomain situ; and invasive carcinoma. The incidence of each group was 47.5, 32.8, 16.4, 3.4, and 0%, respectively. Epithelia of atypical hyperplasia or carcinomain situ were more prevalent in small cystic lesions (less than 4 mm in diameter) than in larger lesions (chi-square test,p<0.05). Epithelia of dilated ductular branches adjacent to cystic lesions showed a similar degree of atypia as the epithelia of the cystic lesions themselves (p<0.01). Epithelial atypia of the main pancreatic duct was mild in all of the cases but two, and was not related to that of the cystic lesion. Among the seven cases of small duct cell carcinoma, two cases had small cancerous cystic lesions, 4.1 and 5.3 mm in diameter, within the tumor. Small cystic lesions appear to have the potential to progress to malignancy but definitive evidence has not been demonstrated. Additional studies, including molecular biological examinations, are necessary to fully understand the biology of these lesions.

Prediction of sensitivity of rectal cancer cells in response to preoperative radiotherapy by DNA microarray analysis of gene expression profiles.

Preoperative radiotherapy has been widely used to improve local control of disease and to improve survival in the treatment of rectal cancer. However, the response to radiotherapy differs among individual tumors. Our objective here was to identify a set of discriminating genes that can be used for characterization and prediction of response to radiotherapy in rectal cancer. Fifty-two rectal cancer patients who underwent preoperative radiotherapy were studied. Biopsy specimens were obtained from rectal cancer before preoperative radiotherapy. Response to radiotherapy was determined by histopathologic examination of surgically resected specimens and classified as responders or nonresponders. By determining gene expression profiles using human U95Av2 Gene Chip, we identified 33 novel discriminating genes of which the expression differed significantly between responders and nonresponders. Using this gene set, we were able to establish a new model to predict response to radiotherapy in rectal cancer with an accuracy of 82.4%. The list of discriminating genes included growth factor, apoptosis, cell proliferation, signal transduction, or cell adhesion-related genes. Among 33 discriminating genes, apoptosis inducers (lumican, thrombospondin 2, and galectin-1) showed higher expression in responders whereas apoptosis inhibitors (cyclophilin 40 and glutathione peroxidase) showed higher expression in nonresponders. The present study suggested the possibility that gene expression profiling may be useful in predicting response to radiotherapy to establish an individualized tailored therapy for rectal cancer. Global expression profiles of responders and nonresponders may provide insights into the development of novel therapeutic targets.

Multicenter Randomized Controlled Trial for the Treatment of Ulcerative Colitis with a Leukocytapheresis Column

The administration of steroids is not always effective for the treatment of ulcerative colitis (UC). Their long-term use often causes adverse effects which sometimes result in their stoppage and acute exacerbation. Therefore, an alternative treatment is necessary in order to decrease steroid dosage and avoid the clinical problems associated with steroids. Methods The effectiveness and adverse effects of a leukocytapheresis (LCAP) were investigated in a controlled multicenter trial with randomized assignment of 76 active-stage UC patients in two groups. In the LCAP group (39 patients), LCAP weekly for 5 weeks as an intensive therapy was added to the on-going drug therapy, while steroids were maintained but not increased, and then LCAP was gradually reduced to once every 4 weeks as a maintenance therapy. In the high dose prednisolone (h-PSL) group (37 patients), PSL was added or increased 30 approximately 40 mg/day for moderately severe and 60 approximately 80 mg/day for severe patients and then gradually tapered. Findings The LCAP group showed a significantly higher effectiveness (74% vs. 38%; p=0.005) and lower incidence of adverse effects (24% vs. 68%; p<0.001). The patients were able to continue the trial for a longer period in the LCAP group than the h-PSL group (p=0.012). Clinical activity and endoscopic indexes showed the LCAP group had better improvements than the h-PSL group. Interpretation The results of the trial show that LCAP permits a reduction in total PSL dosage and is more effective and safer than high-dose PSL administration for intensive therapy, and LCAP may maintain remission longer than PSL.

Randomized, controlled trial of lateral node dissection vs. nerve-preserving resection in patients with rectal cancer after preoperative radiotherapy.

PURPOSE: The effectiveness of preoperative radiation therapy for advanced lower rectal carcinoma to preserve the function of pelvic organs and reduce local recurrences was examined in a prospective, randomized, controlled study. METHODS: Fifty-one patients with a diagnosis of localized and resectable adenocarcinoma of the lower rectum undergoing 50 Gy of preoperative radiotherapy were recruited into the trial between April 1993 and March 1995. The patients were randomly allocated to complete autonomic nerve-preserving surgery without lateral node dissection (D1), or surgery with dissection of the lateral lymph nodes including autonomic nerves (D2) followed by oral administration of carmofur for one year. RESULTS: No difference was observed in either survival or disease-free survival between D1 and D2 groups. There was no difference between the two groups in terms of recurrence rate. A significant difference was observed in urinary and sexual function (P= 0.02 and 0.02, respectively) one year after surgery between D1 and D2 groups. CONCLUSION: This study suggests that lateral node dissection is not necessary in terms of curability for patients with advanced carcinoma of the lower rectum who undergo preoperative radiotherapy.

Prognosis and risk factors of metastasis in colorectal carcinoids: results of a nationwide registry over 15 years

Background: Colorectal carcinoids are often described as low-grade malignant. However, no study has compared the survival between patients with colorectal carcinoids and those with carcinomas, in a large series. In addition, no global consensus has been established on the crucial determinants of metastasis in colorectal carcinoids. Aim: To determine the predictive factors for metastasis in colorectal carcinoids and clarify their prognosis compared with adenocarcinomas. Methods: Data of all patients diagnosed as having colorectal carcinoids were extracted from a large nationwide database of colorectal tumours, the Multi-Institutional Registry of Large-Bowel Cancer in Japan, for the period from 1984 to 1998. Risk factors for lymph node (LN) metastases and distant metastases were analysed among those who were undergoing surgery, by univariate and multivariate analysis. Cancer-specific survival was also compared between patients with colorectal carcinoids and those with adenocarcinomas registered in the same period. Results: Among the 90 057 cases of colorectal tumours that were diagnosed, a total of 345 cases of carcinoids were identified, including 247 colorectal carcinoids of those undergoing surgery. Risk factors for LN metastasis were tumour size ⩾11 mm and lymphatic invasion, whereas those for distant metastasis were tumour size ⩾21 mm and venous invasion. Colorectal carcinoids without these risk factors exhibited no LN metastasis or distant metastasis. Cancer-specific survival of patients with colorectal carcinoids without metastasis was better than that of those with adenocarcinomas. However, the survival was similar between carcinoids and adenocarcinomas if the tumours had LN metastasis or distant metastasis. Conclusions: The presence of metastasis in colorectal carcinoids could lead to survival that is as poor as in adenocarcinomas. Tumours ⩽10 mm and without lymphatic invasion could be curatively treated by local resection, but others would need radical LN dissection.

Anatomical major resection versus nonanatomical limited resection for liver metastases from colorectal carcinoma

BACKGROUND Although systematic anatomical hepatic resection has been reported to improve patient survival in hepatocellular carcinoma, principles of hepatectomy procedure have not been clearly demonstrated in secondary hepatic malignancy. The purpose of the present study was to determine whether selection of surgical procedures for liver resection is associated with the pattern of tumor recurrence or patient survival. METHODS During the period of 1980 through 1999, 174 cases underwent liver resection for hepatic metastasis from colorectal cancer. Of these, 96 underwent systematic anatomical major hepatic resection (anatomical group) and 78 cases underwent nonanatomical limited resection (nonanatomical group). Subset analysis of 115 patients with unilobar single or double tumors was also conducted. RESULTS The overall 5-year survival rate of 174 patients was 43.2%. Univariate analysis did not show a significant difference in patient survival according to surgical procedure (anatomical group versus nonanatomical group). Operative morbidity and mortality rates were slightly higher in anatomical group. From the subset analysis in unilobar single or double tumors, anatomical major hepatectomy was unnecessary in 80.4% of the cases if the tumors were resectable by nonanatomical limited resection. Ninety percent of the ipsilateral recurrence, which could have been avoided if the first operation was anatomical hemihepatectomy, could undergo second hepatectomy with 5-year survival rate of 58.3%. CONCLUSIONS There was not a significant difference in patient survival according to surgical procedure. To minimize surgical stress and operative risk, nonanatomical limited liver resection should be a basic surgical procedure for colorectal metastases.

Multiple primary cancer: an experience at the Cancer Institute Hospital with special reference to colorectal cancer

AbstractBackground. Cancer patients are at high risk of developing a second cancer after the treatment of initial cancers. Understanding the characteristics of multiple primary cancer is important to establish an effective surveillance program for the early detection of second cancers. Methods. We analyzed the cancer registry records from 1986 to 1995 at the Cancer Institute Hospital. The combination of the sites of the index and second cancers and the time intervals between the two cancers were examined. For colorectal cancer, another database of patients between 1946 and 1991 was analyzed, with special reference to synchronous and metachronous cancers. Results. Out of 24,498 registered cases, there were 1281 (5.2%) multiple cancers, of which 464 (1.9%) were in the same organs and 817 (3.3%) were in other organs. Gastric or colorectal cancer frequently developed as the second cancer regardless of the site of the index cancer. Although the majority of the second cancers developed within 3 years after the index cancer, some developed 5 years or more after the index cancer. In colorectal cancer, the cases with metachronous cancer were similar to those with hereditary nonpolyposis colon cancer. The frequent combination of an advanced index cancer and an advanced second cancer and relatively poor survival after the second cancers in the metachronous cases may reflect delayed diagnosis of the second colorectal cancer. Conclusion. Careful attention should always be paid to the second cancer in treating cancer patients. Further analysis by individual site of the index cancers is needed to construct an effective surveillance for second cancers.

Self-limited spontaneous dissection of the main trunk of the superior mesenteric artery

Spontaneous dissection of the splanchnic arteries is rare and reportedly carries a high risk of mortality. Two cases with spontaneous dissection of the main trunk of the superior mesenteric artery followed by a self-limited clinical course are presented. Current management strategies, including bypass operation, patch angioplasty, and conservative treatments, are discussed. Emphasis is placed on the role of nonsurgical management with careful follow-up with the use of new technologies such as duplex and computed tomography scanning.

Bloodless liver resection using the Monopolar Floating Ball plus Ligasure diathermy: Preliminary results of 16 liver resections

Blood loss during liver transection and ischemia-reperfusion injury associated with hepatic inflow occlusion are significant drawbacks during liver surgery. Sixteen patients underwent liver resection using the Monopolar Floating Ball (FB) plus LigaSure (LS) diathermy without occlusion of the hepatoduodenal ligament (group FB-LS). The liver parenchyma was precoagulated using the FB, and the uncovered tiny vessels were sealed using LS. Surgical outcomes were retrospectively compared with 16 well matched patients who underwent liver resection using the conventional clamp crushing method with Pringle’s maneuver (group CC). The amount of blood loss during liver transection was significantly less in group FB-LS than in group CC [200 ml (0–990 ml) vs. 480 ml (120–1800 ml);p = 0.006]. The median time it took to complete the liver transection was significantly longer in group FB-LS than in group CC [144 minutes (43–335 minutes) vs. 58 minutes (18–94 minutes); p < 0.0001]. Hepatic inflow occlusion was temporally used in five patients in group FB-LS to achieve hemostasis in hepatic venous tributaries for 6,10, 19, 26, and 61 minutes, respectively. Using these two electronic devices allows liver resection to be safely performed, with the advantage of minimal blood loss and a reduced inflow occlusion period compared to the conventional method. The major disadvantage may be a slower transection speed. A prospective randomized trial is needed to clarify the clinical benefits of liver resections performed using this novel technique.RésuméLes pertes sanguines lors de la résection hépatique et les lésions d’ischémie-reperfusion en rapport avec la manoeuvre de Pringle (occlusion du pédicule hépatique) sont parmi les inconvénients les plus importants dans la chirurgie hépatique. Seize patients ont eu une résection hépatique utilisant soit la coagulation monopolaire «Floating Ball (FB)» plus « LigaSure (LS)» sans occlusion du pédicule hépatique (groupe FB-LS). Le parenchyme hépatique a été précoagulé par la technique FB et les vaisseaux ainsi découverts ont été coagulés par la LS. L’évolution chirurgicale a été comparée rétrospectivement à celle de 16 patients bien appariés qui ont eu une résection hépatique par des techniques conventionnelles (Kelly clasie) sous clampage pédiculaire (groupe CC). La quantité de sang perdu pendant la résection hépatique a été significativement moins élevé dans le groupe FB-LS que dans le groupe CC [200 (0–990) vs. 480 (120–1800) ml, p = 0.006]. La durée médiane de la résection hépatique a été significativement plus longue dans le groupe FB-LS que dans le groupe CC [144 (43–335) vs. 58 (18–94) min, p < 0.0001]. Dans le groupe FB-LS, l’occlusion par clampage pédiculaire hépatique a été utilisé temporairement chez cinq patients afin d’obtenir une hémostase active à partir des branches hépatiques veineuses pendant 6, 10, 19, 26, et 61 minutes. Par l’utilisation de ces deux appareils électroniques, la résection hépatique peut être réalisée avec sécurité avec un minimum de pertes sanguines et une durée d’occlusion pédiculaire réduite par rapport aux techniques conventionnelles. L’inconvénient majeur est la durée plus longue nécessaire à la transection. Une étude prospective randomisée est nécessaire pour clarifier les bénéfices réels pour les résections hépatiques avec cette nouvelle technique.ResumenLa hemorragia en la sección transversal del hígado y el síndrome de isquemia-reperfusión tras la oclusión del flujo sanguíneo hepático constituyen serios problemas en la cirugía del hígado. 16 pacientes fueron sometidos a una resección hepática sin oclusión del ligamento hepatoduodenal empleando el Monopolar Floating Ball (FB) y la diatermia Liga Sure (LS). El parénquima hepático fue cauterizado utilizando el FB y los pequeños vasos sellados empleando el LS. Los resultados quirúrgicos fueron comparados retrospectivamente con un grupo homogéneo de 16 pacientes sometidos a resección hepática convencional utilizando la pinza de forcipresión de Storm junto con la maniobra de Pringle (grupo CC). La hemorragia tras la sección hepática fue significativamente menor en el grupo FB-LS que en el grupo CC [200 (0–990) trente a 480 (120–1800) ml, p = 0.006]. La duración media de la sección hepática fue significativamente mayor en el grupo FB-LS que en el grupo CC [144 (43–335) trente a 58 (18–94) minutes, p < 0.0001]. 5 pacientes del grupo FB-LS precisaron de oclusión temporal del flujo sanguíneo hepático, durante 6, 10, 19, 26, y 61 minutes para realizar la hemostasia de venas hepáticas colaterales. Utilizando dos aparatos electrónicos, la resección hepática puede efectuarse, sin peligro alguno, produciéndose una hemorragia escasa, al mismo tiempo que se minimiza el periodo de oclusión del flujo sanguíneo hepático con relación a la técnica operatoria convencional. La gran desventaja de este proceder viene dada por la lenta velocidad de la sección hepática. Se precisan estudios prospectivos randomizados para aclarar la utilidad clínica de la resección hepática efectuada mediante esta nueva técnica.