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M Yasutomi

Publications and source records attributed to M Yasutomi.

At least 19 recordsLinked to original sources

The extent of lymph node dissection for colon carcinoma: the potential impact on laparoscopic surgery.

BACKGROUND: The surgeon is no longer able to palpate the mesocolon for lymph node metastases during laparoscopic colectomy. The extent of lymph node dissection should be determined beforehand for cancer control. METHODS: The distribution of lymph node metastases was obtained by the clearing method on colon carcinomas for 164 patients. RESULTS: For pericolic spread: for pT1 tumors, the distance from the primary tumor to a metastatic lymph node was 2.5 cm; for pT2, the distance was within 5 cm; for 97.0 % of pT3 tumors with lymph node metastases, the distance was within 7 cm; for 93.3 % of pT4 tumors with lymph node metastases, the distance was within 7 cm. For central spread: for pT1 tumors, the rate of metastasis to central lymph nodes was 0 %; for pT2, the rate of metastasis was 20.0 % to intermediate lymph nodes; for pT3, the rate of metastasis was 30.6 % to intermediate lymph nodes and 15.3 % to main lymph nodes; for pT4, the rate of metastasis was 44.4 % to intermediate lymph nodes and 22.2 % to main lymph nodes. CONCLUSIONS: Central lymph node dissection is not required for patients with T1 carcinomas, but proximal and distal 3-cm margins of resection are required. For T2, central lymph node dissection that includes the intermediate lymph node should be performed, as well as 5-cm proximal and distal margins of resection. For T3 and T4, central lymph node dissection including the main lymph node should be performed, as well as 7-cm proximal and distal margins of resection. [See editorial on pages 177-8, this issue.]

Colectomy

The importance of neural invasion (NI) as a prognostic factor in diffuse invasive gastric cancer.

The relationship between histological factors, including neural invasion (NI), and survival rates in patients with Borrmann type IV diffuse invasive gastric cancer was examined to determine the significance of NI as a prognostic factor. NI was studied histochemically in 75 patients who underwent resection after 1982, 37 of whom underwent curative resection. The 3-year and 5-year survival rates of the 37 patients who underwent curative resection were 37.2% and 12.7%, respectively. Recurrence was detected as peritoneal dissemination in 19 of those patients (82.6%), and the most significant prognostic factor was the depth of wall invasion (P < 0.01). While NI (P = 0.06) and lymph node metastasis (P = 0.09) appeared to be prognostic factors, there were no significant differences. Therefore, the depth of wall invasion was classified as T2 and T3 or 4 to examine the association of NI and lymph node metastasis with prognosis, whereby NI was shown to be a significant prognostic factor in T2. In conclusion, NI may be a significant prognostic factor in patients with wall invasion of T2 without serosal invasion, as it provides a pathway for the progression to peritoneal dissemination.

Disease Progression

Measurement of portal venous flow velocity with an implantable miniature Doppler probe in pig liver transplantation.

Portal venous flow (PVF) was serially monitored after pig liver transplantation (LTX) with the use of an implantable, miniature Doppler probe developed in our laboratory. Throughout the study period, the mean PVF in pigs that underwent LTX was significantly greater than that in pigs that were sham operated. For three animals with early graft failure secondary to primary nonfunction and for six that survived longer than 7 days, the mean PVF on postoperative day (POD) 1 was 18.7 +/- 3.8 cm/s and 41.7 +/- 11.2 cm/s, respectively (P < 0.05). For animals with acute cellular rejection (ACR), the mean PVF was 61.3 +/- 9.9 cm/s on POD 7 and 54.3 +/- 6.38 cm/s on POD 14. These values were significantly higher than those for animals without ACR (P < 0.05). Moreover, the increase in PVF correlated well with the degree of ACR. The actual PVF volume was measured by ex vivo perfusion, which showed a clear correlation with the PVF velocity obtained with the implanted, miniature Doppler probe. We feel that the liver graft requires increased PVF volume after transplantation to facilitate functional recovery from damage to hepatocytes due to preservation-reperfusion injury, and that ACR is also associated with an increased PVF. We conclude that monitoring the PVF in the early postoperative period after LTX is useful in the evaluation of graft function, particularly for predicting primary nonfunction and severity of ACR.

Animals

Evaluation of tetrahydropyranyladriamycin as an immunosuppressant in concordant xenotransplantation.

BACKGROUND: Tetrahydropyranyladriamycin (THP), a derivative of anthracycline, exhibits a stronger antiproliferative activity and a lower cardiotoxicity than the other anthracyclines. The value of THP as an immunosuppressant has not been examined yet, whereas cyclophosphamide, which is another antiproliferative drug, has shown promise as an immunosuppressant in concordant xenotransplantation. METHODS: The effect of THP on the marginal zone in the spleen and anti-species antibody production was evaluated and was compared with that of cyclophosphamide in a concordant xenogeneic splenocyte injection model (hamster-to-rat). Next, THP was used as monotherapy for hamster-to-rat heart transplantation to substantiate the potency of its immunosuppressive activity in concordant xenotransplantation. Finally, combination therapy with THP plus FK506 was tried. RESULTS: THP (5 mg/kg) suppressed the expansion of the marginal zone more than did cyclophosphamide (40 mg/kg) and inhibited the production of antispecies antibody as much as did cyclophosphamide (40 mg/kg) in the splenocyte injection model. THP monotherapy could prolong the survival of hamster-to-rat heart grafts up to 14.5 +/- 3.2 days (n = 21). The rejected grafts in the THP-treated animals did not show any histologic evidence of vascular endothelial damage but did exhibit a mononuclear cell infiltration. Combination therapy with THP plus FK506 provided excellent graft survival. CONCLUSIONS: THP can prevent early phase humoral rejection in concordant xenotransplantation.

Animals

Does lateral lymph node dissection improve survival in rectal carcinoma? Examination of node metastases by the clearing method.

BACKGROUND: The treatment of rectal carcinoma by lateral lymph node dissection has risks and benefits. Therefore, we investigated the therapeutic efficacy of lateral lymph node dissection. STUDY DESIGN: We studied 198 patients with rectal carcinoma who underwent lateral lymph node dissection. Metastases to the lymph nodes were examined by the clearing method. The incidence of urinary and male sexual dysfunction was determined by measuring the residual urine volume and individual interview 1 year after operation. RESULTS: The rate of metastasis to lateral lymph nodes was 11.1 percent, and metastasis to the lateral lymph nodes occurred more frequently with lower rectal carcinoma classified as pT3 or pT4 in the TNM system. The rate of local recurrence was 12.5 percent and the 5-year survival rate after curative resection was 70.1 percent. The 5-year survival rate in patients with metastasis to the lateral lymph nodes was 25.1 percent, and this rate was significantly lower than the 5-year survival rate of 74.3 percent in patients without metastasis to the lateral lymph nodes. Urinary dysfunction was observed in 67.5 percent of patients, and male sexual dysfunction was found in 97.4 percent of men younger than 60 years of age with prior sexual ability. CONCLUSIONS: The prognosis for patients with metastasis to the lateral lymph nodes is poor, and the improvement in survival rate from lateral lymph node dissection is minimal.

Female

Lymph node metastases detected in the mesorectum distal to carcinoma of the rectum by the clearing method: justification of total mesorectal excision.

BACKGROUND: Total mesorectal excision effectively reduces the local recurrence rate of carcinoma of the rectum. This study was undertaken to clarify the rationale for total mesorectal excision. STUDY DESIGN: We retrospectively reviewed the records of 198 patients who underwent resection of a carcinoma of the rectum. The presence of nodal metastases in the mesorectum distal to the primary tumor was examined by the clearing method. RESULTS: The metastatic rate in the distal mesorectum was 20.2 percent. The metastatic rates according to the extent and site of the tumor were as follows: pT1, 0 percent; pT2, 0 percent; pT3, 21.9 percent; pT4, 50 percent; rectosigmoid, 10 percent; upper rectum, 26.3 percent; and lower rectum, 19.2 percent. The longest distal spread from the primary tumor to the metastatic node was 2 cm in carcinoma of the rectosigmoid, 4 cm in carcinoma of the upper rectum, and 3 cm in carcinoma of the lower rectum. CONCLUSIONS: Total mesorectal excision is required for patients with T3 and T4 tumors in the lower rectum, and excision of all mesorectal tissue down to at least 5 cm below the tumor is required for patients with T3 and T4 tumors in the upper rectum.

Humans

Prognostic factors for patients with colon or rectal carcinoma treated with resection only. Five-year follow-up report.

BACKGROUND: The prognostic factors and natural history of recurrence in patients with colorectal carcinoma who underwent curative resection and no other therapy were analyzed. METHODS: The object of analysis was the potentially curative resection only subgroup in the randomized clinical trial (RCT) that we performed. Cox's proportional hazards model was used mainly to analyze recurrence rates during the first 5 years after surgery. RESULTS: The analysis was performed on a subgroup of the RCT (279 patients with colon carcinoma and 293 patients with rectal carcinoma). Five-year disease free survival rates were 76.3% and 56.5% for colon and rectal carcinomas, respectively. The prognostic factors for recurrence for colon carcinoma patients were different from those with rectal carcinoma. For colon carcinoma, only Dukes stage was significant, whereas for rectal carcinoma, Dukes stage, age, location of the tumor, and serosal and venous invasion by cancer cells were prognostic factors. Log-transformed disease free survival rates were linear in Dukes Stage B and biphasic in Dukes Stage C for both colon and rectal carcinoma. The two phases in Dukes Stage C intersected at 2.85 and 3.04 years, respectively. The annual hazard value was high for the first 3 years in both colon and rectal carcinoma. CONCLUSIONS: We conclude that follow-up of patients with colorectal carcinoma who undergo potentially curative resection is of particular importance in the first 3 years after surgery. Furthermore, the usefulness of adjuvant chemotherapy can be adequately evaluated from data yielded during this postoperative period.

Chemotherapy, Adjuvant

Allelic loss of chromosome 17p, mutation of the p53 gene, and microsatellite instability in right- and left-sided colorectal cancer.

BACKGROUND: Epidemiologic and genetic studies suggest that cancer of the right and left sides of the bowel arise through different mechanisms. To investigate the molecular mechanisms, allelic loss of chromosome 17p, p53 mutations, and microsatellite instability were analyzed in colorectal cancer according to tumor site. METHODS: Using the polymerase chain reaction and single strand conformation polymorphism (PCR-SSCP) method, mutations within exons 5-8 of the p53 gene were examined in 108 colorectal cancers including 30 right-sided and 78 left-sided colorectal cancers. Allelic loss of chromosome 17p was studied by restriction fragment length polymorphism analysis, and genetic instability was examined for replication error (RER) at three microsatellite loci on chromosomes 2p, 17p, and 17q. RESULTS: Allelic loss was observed in 61% (14 of 23 informative cases) of right-sided tumors and in 60% (26 of 43 informative cases) of left-sided tumors. PCR-SSCP analysis demonstrated that 63 of 108 tumors had a mutated p53 gene in exons 5, 6, 7, or 8. When comparing the frequency of mutation in each exon based on tumor site, the frequency of mutation in exon 8 in right-sided (2 of 18 informative cases) tumors was significantly lower than that observed in left-sided (17 of 45 informative cases) tumors. RER(+) was observed in 43% of right-sided tumors, whereas 24% of left-sided tumors were RER(+). Although the difference was not statistically significant, a trend was observed between RER(+) phenotype and tumor site. CONCLUSIONS: Our results suggest that the molecular mechanisms of colorectal carcinogens may differ between right- and left-sided tumors.

Alleles

Immunohistochemical analysis of p53 and ras p21 expression in colorectal adenomas and early carcinomas.

To further investigate whether multiple genetic changes are involved in the development of colorectal cancer, we performed an immunohistochemical analysis of p53 and ras p21 protein expression in 139 specimens of colorectal adenoma with varying degrees of dysplasia, 57 specimens of early cancer with an adenomatous component, and 12 specimens of superficial early cancer without any adenomatous component. Positive p53 staining was found in 15% of the adenomas with moderate dysplasia and in 42% of the adenomas with severe dysplasia or intramucosal carcinoma (IMCA). Positive immunostaining of p53 was observed to be significantly correlated with the degree of dysplasia and the depth of invasion, as was the expression of ras p21. However, a closer correlation was observed with the increasing size of the adenomas. Furthermore, p53 staining was positive in 42% of the 12 superficial early cancer specimens, while ras staining was positive in only 1 specimen (8%). These results indicate that p53 gene overexpression may play some biological role in both the adenoma-to-carcinoma sequence and in de novo cancer development, whereas ras p21 expression may not be as involved in de novo cancer development as in the malignant conversion of colorectal adenomas.

Adenomatous Polyps

IL-2 perfusion to the liver augments the hepatic extraction rate of accompanying anticancer drugs.

A pilot study we conducted on hepatic infusion chemotherapy combined with interleukin-2 (IL-2) for metastatic liver malignancies revealed very encouraging results indicating that this treatment modality is more effective than either of the anticancer drugs used alone. To clarify the mechanisms underlying the synergism of these modalities, the pharmacokinetics of anticancer drugs were examined in a rat model. Adult rats were given 5-fluorouracil (5-FU) or mitomycin C (MMC) combined with various doses of IL-2 up to 7500 JRU/kg per minute for the measurement of hepatic extraction rates (HER). The HER of 5-FU was significantly increased (P < 0.01) in combination with IL-2 in a dose-dependent fashion while that of MMC also showed a tendency to increase. Thus, it is conceivable that the increase of vascular permeability caused by IL-2 results in augmentation of the HER of associated anticancer drugs. This effect may improve the delivery of anticancer drugs to the liver and alleviate general toxicity by reducing the amount of circulating anticancer agents.

Animals

Liberation of vasoactive substances and its prevention with thromboxane A2 synthase inhibitor in pig liver transplantation.

There are multiple causes of liver graft nonfunction in the early post-transplant period. Since a severe microcirculatory disturbance based on ischemia-reperfusion liver injury is considered to be the main underlying pathophysiology, it is suspected that various vasoactive substances are liberated after reperfusion of the graft. In order to investigate this matter, we conducted an experimental study with pig liver allotransplantation. Two groups of animals received donor grafts with or without thromboxane synthase inhibitor (sodium ozagrel), 1.25 mg/ kg body weight intravenously, given at the time of liver harvesting. All of the recipient animals in the treatment group (n = 10) survived longer than 7 days whereas three of ten animals in the control group died within 7 days. Serum lactate dehydrogenase (LDH) in the recipient serum at 1 h after reperfusion was significantly lower in the treatment group (915.1 +/- 167.3 U/l) than in the control group (1264.4 +/- 134.7 U/l). Serum thromboxane B2 (2261.7 +/- 1055.7 pg/ml) and endothelin-1 (6.3 +/- 2.2 pg/ml) after reperfusion in the treatment group were significantly lower than those in the control group (4220.0 +/- 1711.0 pg/ml and 11.2 +/- 3.1 pg/ml, respectively). Although serum angiotensin II after reperfusion tended to be lower in the treatment group than in the controls serum renin activity was less than 3 ng/ml in both groups of animals. There were no differences in the plasma endotoxin levels between the two groups. We conclude that the administration of sodium ozagrel to the donor animals provided better graft function in recipients than no such treatment. We speculate that the inhibition of thromboxane A2 production suppresses the liberation of other vasoconstrictive substances, preventing microcirculatory disturbance and, thereby, contributing to improved graft function after liver transplantation.

Angiotensin II

Second-look operation for recurrent colorectal cancer based on carcinoembryonic antigen and imaging techniques.

PURPOSE: The usefulness of postoperative carcinoembryonic antigen (CEA) monitoring and improvements in imaging techniques have renewed enthusiasm for second-look operations (SLO) as the most effective treatment for recurrent colorectal cancer by reresection following early detection. The aim of our study is to evaluate the role of CEA and imaging techniques-directed SLO. METHODS: Seven hundred fifty-six patients with Dukes Stages B and C, who had undergone curative resection, were monitored postoperatively using CEA and imaging techniques. An SLO was performed on any potentially resectable recurrence, and in addition, an SLO was done when a persistently rising CEA value was detected. RESULTS: Recurrence developed in 18.8 percent (142/756) of patients, and 90.8 percent (129/142) of the recurrences were detected within the first three years following curative resection. When comparing carcinomas of the colon with that of the rectum, the former were associated with significantly more hepatic and intraabdominal recurrences, whereas the latter had significantly more locoregional and pulmonary recurrences. Seventy-two patients underwent SLO. Of these patients, 54.2 percent (39/72) had all of their disease resected, and 1.4 percent (1/72) had no detectable disease at the SLO. Among the 142 patients with recurrence, 71 (50 percent) patients underwent SLO. The resectable group at SLO carried a significantly better survival than the unresectable recurrence group (41.3 vs. 5.2 percent; P<0.01). CONCLUSIONS: Complete removal of colorectal cancer recurrences by SLO, on the basis of postoperative, follow-up CEA and imaging technique findings, results in improved survival.

Actuarial Analysis

Functional outcome after low anterior resection with low anastomosis for rectal cancer using the colonic J-pouch. Prospective randomized study for determination of optimum pouch size.

PURPOSE: Functional outcome after low anterior resection with ultralow coloanal anastomosis for rectal cancer is improved by construction of a colonic J-pouch vs. straight anastomosis. Optimum size of this pouch has yet to be determined. Therefore, we initiated a prospective, randomized trial using 5-cm and 10-cm pouches to determine this size. METHODS: Patients with tumors 5 to 10 cm from the anal verge were included in the study. Before a low anterior resection anastomosis was performed, patients were randomized to either a 5-cm J-pouch group (5-J group) or a 10-cm J-pouch group (10-J group). Functional assessments were performed one year postoperatively. Clinical functions were evaluated using a functional scoring system. Physiologic functions, such as sphincter and reservoir function, were evaluated by anorectal manometry and evacuation function by the balloon expulsion and saline evacuation tests. RESULTS: Forty patients among 43 randomized patients were assessed for functional outcome one year postoperatively (5-J group, n = 20; 10-J group, n = 20). The functional score was similar for the two groups, although reservoir function in the 5-J group was significantly less than in the 10-J group. Sphincter function was similar between the two groups. Evacuation function in the 5-J group was significantly superior to that in the 10-J group. CONCLUSIONS: The 5-cm J-pouch conferred adequate reservoir function without compromising evacuation.

Adult

Analysis of regional lymph node metastases from rectal carcinoma by the clearing method. Justification of the use of sigmoid in J-pouch construction after low anterior resection.

PURPOSE: It has been reported that functional outcome following low anterior resection of resection of rectal cancer is improved by construction of a colonic J-pouch compared with straight anastomosis. Hence, we tried to justify use of the sigmoid colon in the construction of a J-pouch by the analysis of regional lymph node metastases. METHODS: A total of 182 patients underwent resection for rectal cancer. Node metastases were examined by the clearing method. According to Japanese General Rules for Clinical and Pathological Studies on Cancer of the Colon, Rectum and Anus (JGR), nodes were classified into the perirectal nodes (PR-N), pericolic nodes (PC-N), central intermediate nodes (C-IM-N), central main nodes (C-M-N), lateral intermediate nodes (L-IM-N), and lateral main nodes (L-M-N). RESULTS: Metastatic rate (number of patients with node metastases/total number of patients) of PR-N was 57.1 percent. Metastatic rate of C-IM-N was 18.7 percent and that of C-M-N was 7.1 percent. Metastatic rates of L-IM-N and L-M-N were 8.8 and 3.3 percent, respectively, and both were highest in the case of lower rectal cancer. Metastatic rate of PC-N was only 1.1 percent. The number of cases without node metastases (n(-) cases) was 78, that with only PR-N metastases (PR-N cases) was 63, that with intermediate but not main node metastases (IM-N cases) was 29, and that with main node metastases (M-N cases) was 12. Five-year survival rate after curative resection was 88.5 percent for n(-) cases, 70.9 percent for PR-N cases, 65.9 percent for IM-N cases, and 41.7 percent for M-N cases. CONCLUSIONS: In low anterior resection, high ligation of the inferior mesenteric artery and dissection of C-M-N, C-IM-N and PR-N are necessary, with the addition of the L-IM-N and L-M-N in the case of lower rectal cancer. Resection of sigmoid colon is not required, and therefore, a J-pouch can be constructed using the sigmoid colon. Nodal classification according to the JGR was predictive of case distribution and five-year survival rate.

Anastomosis, Surgical

Measurement of 5-fluorouracil in scalp hair: a possible index of patient compliance with oral adjuvant chemotherapy.

OBJECTIVE: Little is known about patient compliance with oral adjuvant chemotherapy. It is estimated to be poor especially in Japan, where it is still unusual for patients to be directly informed of their diagnosis of malignancy. 5-Fluorouracil (5-FU) was measured in hair samples to assess patient exposure to 5-FU, and its potential usefulness is discussed as an index of compliance with postoperative adjuvant chemotherapy. METHODS: Hair samples obtained from 55 patients, who had received oral 5-FU (total dose 27-41 g) as postoperative adjuvant chemotherapy over a 6-month period, were used for the analysis of 5-FU. The drug was extracted from the hair using ethyl acetate, and its fluorescence derivatization was employed for measurement with HPLC. The detection limit of 5-FU in hair was 0.01 ppm. RESULTS: In 22 out of 55 samples 5-FU content was under the detection limit, whereas in the remaining 33 samples the drug was detected in a range of 0.006-2.125 ng per hair strand; in addition, drug content showed a lognormal distribution. 5-FU was detected in the hair collected from those patients who were possibly compliant with the postoperative oral adjuvant chemotherapy. CONCLUSION: As many as 40% of the patients analysed were supposed to be much less compliant. Even in the possibly compliant patients, the degree of compliance with the therapy varied according to a log-normal distribution.

Animals

Prognostic factors of colorectal cancer. Results of multivariate analysis of curative resection cases with or without adjuvant chemotherapy.

One thousand two hundred fifty-four cases (610 colonic and 644 rectal cancers resected during 2 years from 1984 and followed up for more than 5 years) were entered from 140 institutions in Japan and analyzed by means of Cox's proportional hazards model. The analyzed pathologic variables were the size and depth of invasion, Dukes' stage, venous invasion, lymphatic permeation, and other clinical features, such as the sex and age of the patient and location of the tumor. The extent of dissection, serum carcinoembryonic antigen (CEA) level, and the presence or absence of adjuvant chemotherapy were also analyzed. Adjuvant chemotherapy consisted of three arms for both colonic and rectal cancers. For colonic cancer, arm I was a combination of i.p. (intraportal) and i.v. mitomycin C (MMC) + p.o. 5-fluorouracil (5-FU); arm II was i.v. MMC + p.o. 5-FU; and arm III was surgery only. For rectal cancer, arm IV was a combination of i.a. (inferior mesenteric artery) and i.v. MMC + p.o. 5-FU; arm V was i.v. MMC + p.o. 5-FU; and arm VI was surgery only. As for the factors affecting the disease-free survival of the patient, multivariate analysis disclosed nodal involvement, venous invasion, an elevated CEA level, and the lower part of the rectum. The effect of adjuvant chemotherapy on the patient's survival was proven for rectal cancer but not for colonic cancer. We conclude that these factors should be considered in setting the stage of tumor pre- and postoperatively.

Aged