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Biomedical subjects

K Sugimachi

Publications and source records attributed to K Sugimachi.

At least 19 recordsLinked to original sources

Prediction of early and late recurrence after curative resection for gastric carcinoma.

BACKGROUND: Although several prognostic factors for patients with gastric carcinoma have been demonstrated, those predictive of early and late recurrences after surgery are still unclear. METHODS: Of 479 patients who underwent curative resection for gastric carcinoma from 1977 to 1987, 115 patients who died of recurrence were studied. RESULTS: The patients were divided into 2 groups: an early recurrence group that included 80 patients who died within 3 years after surgery, and a late recurrence group, that included 35 patients who died more than 3 years after surgery. Early recurrence was characterized by a large tumor (8.1 cm vs. 6.7 cm; P<0.05) and many involved lymph nodes (7.7 vs 4.4; P<0.01). However, the depth of invasion, as well as the level of positive lymph nodes were not different between the two groups. Multivariate analysis showed that tumor size and the number of positive lymph nodes independently influenced the survival period. CONCLUSIONS: Tumor size and the number of positive lymph nodes are the most important factors predicting the timing of recurrence after curative resection for gastric carcinoma.

Female

An integrated microsatellite length analysis using an automated fluorescent DNA sequencer.

Analyzing microsatellite instability (MI) in malignant tumors is thought to be useful for screening cancer patients to identify those patients with a higher risk of developing second malignant tumors. In this paper, we report a new, accurate, and efficient method of detecting MI using an automated fluorescent DNA sequencer and a computer that automatically calculates the size, height, and area of each fluorescent product, making it possible to assess MI more accurately and more rapidly. The primers for amplification of each microsatellite locus are labeled by two different fluorescent dyes, rox (red) and fam (blue). The rox-labeled primer was used for the tumor, whereas the fam-labeled primer was used for the corresponding normal tissue. Two amplified products from both the tumor and the normal tissue were co-loaded into a single lane of the sequencing gel and were analyzed. MI could be detected based on the presence of different waving patterns. Furthermore, several loci could also be analyzed simultaneously for MI in a single lane. Using this method, we examined the frequency of MI in gastric cancer. The results showed that 5 of 22 (22.7 %) gastric cancers were MI-positive, which corresponds to the findings of previous reports that used the radioisotopic method. The improved method may open up the possibility of performing routine examination of MI in many cancer patients and offers hope for the potential clinical application of Ml analysis as a follow-up evaluation of cancer patients.

Chromosome Aberrations

Factors correlated with portal venous invasion by hepatocellular carcinoma: univariate and multivariate analyses of 232 resected cases without preoperative treatments.

BACKGROUND: The postoperative intrahepatic recurrence of hepatocellular carcinoma (HCC) is high. It is difficult to distinguish whether the recurrence is metastatic or new primary lesion. To determine the malignant potential of HCC itself, we analyzed the risk factors associated with portal venous invasion since this is direct evidence of tumor invasiveness. METHODS: Two hundred and thirty-two patients who underwent curative hepatectomy for HCC without preoperative treatments were included in this study, because preoperative treatment caused the tumor to undergo a variety of histologic change. We analyzed the risk factors linked to portal venous invasion by both univariate and multivariate analyses. RESULTS: In an univariate analysis, tumors larger than 3 cm, high histologic grade (III or IV), the presence of fibrous capsule, necrosis, mitotic rate of more than 4/10 high power fields, peliotic change, presence of tumor giant cells, high platelet count, low level of indocyanine green retention rate at 15 minutes, and the absence of cirrhosis were significantly correlated with portal venous invasion. In multiple stepwise logistic regression analysis, tumors larger than 3 cm, high histologic grades, and the presence of fibrous capsule were strong predictors of portal venous invasion by HCC. CONCLUSIONS: Because the blood vessels of the fibrous capsule were frequently invaded by cancer cells, it may have been possible to prevent postoperative metastatic recurrence if HCC were resected before becoming large enough to have a fibrous capsule.

Adult

Age-related characteristics of gastric carcinoma in young and elderly patients.

BACKGROUND: The clinicopathologic features of young and elderly patients with gastric carcinoma have been analyzed. METHODS: We analyzed the data from 174 patients with gastric carcinoma age 40 years and younger and from 356 patients with gastric carcinoma age 70 years and older who were surgically treated at the Department of Surgery II, Kyushu University, Japan. RESULTS: The rate of multiple gastric carcinomas was 2.9% (5/174) for the young patients and 13.2% (47/356) for the elderly. In subjects older than 70 years, male patients predominated, tumors were smaller, differentiated lesions more common, vascular involvement more frequent, tumors were less infiltrative, and the rate of liver metastasis was higher. For patients younger than age 40 years, undifferentiated type with infiltrative growth was frequent and the rate of liver metastasis was higher. There were no differences in the positive rate of p53 overexpression and the proliferating activity of the cancer cells determined by PCNA LI, between the young and elderly patients. The survival rate after curative resection was lower for the elderly compared with that for the young patients; hematogenous recurrence was higher in the former. CONCLUSIONS: The clinicopathological features of gastric carcinoma differed between the young and elderly patients, and these differences should be considered when age-oriented treatment is being designed.

Adult

What is the earliest malignant lesion in the esophagus?

BACKGROUND: The incidence of early esophageal cancer is definitely increasing due to recent advances in diagnostics. When we discuss early carcinoma of the esophagus, however, there is still controversy as to whether dysplasia is either benign or the earliest malignant lesion. METHODS: Nineteen resected esophaguses with both cancer and dysplasia (including 19 cancers concomitant with 26 dysplastic lesions) were studied for expression of p53 protein. RESULTS: Immunohistochemical overexpression of p53 protein in esophageal dysplasia is almost the same as that in cancer. CONCLUSIONS: Esophageal dysplasia should be recognized as the earliest malignant lesion which already demonstrates cancerous features although it is not immediately critical. A routine endoscopic Lugol's solution test is very useful for both detection and following-up of the early nests in the esophagus. These lesions are good candidates for endoscopic mucosal resection for the purpose of accurate diagnosis or curative treatment.

Esophageal Neoplasms

Transforming growth factor-beta 1 induces apoptosis in gastric cancer cells through a p53-independent pathway.

BACKGROUND: Apoptosis is induced by various anticancer agents or radiation through the tumor suppressor gene p53-dependent pathway and is also induced by other factors, including transforming growth factor-beta 1 (TGF-beta 1). In this study, the authors investigated whether TGF-beta 1 would induce apoptosis in gastrointestinal cancer cells, and its relation to the status of the p53 gene. METHODS: The induction of apoptosis by TGF-beta 1 was determined in 12 gastrointestinal cancer cell lines using DNA ladder formation. Status of the p53 gene was examined by sequencing of cDNA from p53 mRNA and expressions of TGF-beta 1 mRNA and TGF receptors I and II mRNAs were determined by Northern blot analysis and the reverse transcriptase-polymerase chain reaction analysis, respectively. RESULTS: Of 12 cell lines, wild-type p53 was present in 3 lines, point mutation was detected in 7 lines, and p53 mRNA was absent in 2 lines. TGF-beta 1 was expressed in all 12 lines, but both TGF receptors I and II were expressed in only 6 lines. Addition of TGF-beta 1 induced DNA ladder formation only in KATOIII cells, with deleted p53 mRNA, but expressed TGF receptors I and II. CONCLUSIONS: These findings show that TGF-beta 1 induces apoptosis in gastric cancer cells through TGF-beta receptors I and II and a p53-independent pathway.

Antineoplastic Agents

Expression of ornithine decarboxylase mRNA in gastric carcinoma.

BACKGROUND: Ornithine decarboxylase (ODC) is a key rate-limiting enzyme in polyamine biosynthesis. Several studies using an enzyme assay revealed that the ODC activity was higher in tumor tissue than in normal tissue. However, there is little information on the mRNA status of ODC in surgical specimens. ODC is a transcriptional target gene of c-myc. METHODS: cDNA was obtained by reverse transcription (RT) from fresh specimens of 56 surgical pairs of primary gastric carcinomas and corresponding normal tissue specimens. The ODC and c-myc mRNAs were subsequently detected by means of the polymerase chain reaction. The tumor/normal (T/N) ratio of ODC expression was calculated after correcting for glyceraldehyde-3-phosphate dehydrogenase as an internal control. The T/N ratio of ODC was plotted against that of c-myc. RESULTS: The corrected expression levels of ODC mRNA in the tumor were greater than those of the normal mucosa in 36 of 56 cases (64%). The cases of tumor with vascular vessel invasion showed a higher T/N ratio than those without vascular invasion (P < 0.01). Similarly, female patients showed a higher T/N ratio than male patients (P < 0.01). There was a significant correlation between the expressions of both ODC and c-myc genes (P < 0.05). CONCLUSIONS: The findings imply that (1) overexpression of ODC mRNA in tumor tissue may correlate with aggressive biologic behavior, such as vascular vessel invasion, and (2) there is an intimate correlation between ODC and c-myc genes.

Base Sequence

Multidrug resistance-associated protein expression in clinical gastric carcinoma.

BACKGROUND: We examined the relationship between the expression of a multi-drug resistance-associated protein (MRP) and the biologic factors regarding invasion and metastasis of human gastric cancer. METHODS: In 75 patients with gastric cancer, the expression of MRP was immunohistochemically investigated and the expression of MRP mRNA was also detected using reverse transcription PCR (RT-PCR). Sensitivity to the anticancer agents, cisplatin (CDDP), doxorubicin (DXR), etoposide (VP-16), and mitomycin C (MMC) was examined using the MTT {3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl[2H]-tetra-zolium bromide} assay. The relation between MRP expression and development, invasion, and metastasis of cancer was analyzed, and overexpression of the tumor suppressor gene p53 was investigated, immunohistochemically. RESULTS: Immunohistochemically detected MRP positive tumors were noted in 34 of 75 excised tumors (45%), and confirmed by RT-PCR. There was no significant relation between MRP expression and clinicopathologic features or prognosis. Positive p53 staining was evident in 16 of 34 MRP positive tumors (47%) and 18 of 41 negative ones (44%), and there was no significant correlation between MRP and abnormal p53 expression. The MTT assay showed that MRP positive gastric cancer tissue was less sensitive to CDDP, DXR, and MMC compared with MRP negative ones. A similar tendency was noted with VP-16. CONCLUSIONS: MRP expression relates to the chemosensitivity of tumor cells against some anticancer drugs and is independent of known factors related to the development, invasion, and metastasis of human gastric cancers.

ATP-Binding Cassette Transporters

Microvessel quantification and its possible relation with liver metastasis in colorectal cancer.

BACKGROUND: Several studies have proven the usefulness of microvessel quantification as a prognostic factor for patients with various malignant tumors. The aim of this paper was to clarify the relationship between microvessel density (MVD) as a parameter of tumor angiogenesis and liver metastasis in colorectal cancer. METHODS: A total of 175 patients with advanced colorectal cancer were evaluated (58 with concurrent liver metastases). Microvessel quantification was performed immunohistochemically, using monoclonal antibodies against endothelial protein Factor VIII-related antigen (F8RA) and against endothelial surface marker CD34. Finally, the relationship between MVD and liver metastasis was analyzed. RESULTS: A significant correlation was observed between MVD for F8RA and MVD for CD34 (n = 175, r = 0.9560, P = 0.0001). MVD in the tumors stained for F8RA ranged from 15.2 to 78.6 microvessels per x 200 field (mean 32.8 +/- 11.7), while the tumors with liver metastatic disease compared with the tumors without liver metastasis (F8RA; mean 36.1 +/- 11.3 vs. 31.2 +/- 11.5, P = 0.0090; CD34; mean 64.4 +/- 20.4 vs. 52.0 +/- 19.4, P = 0.0010). CONCLUSIONS: Microvessel quantification within a colorectal tumor using immunohistochemical staining methods has shown a significant correlation between MVD and liver metastasis. Tumors with a greater MVD may thus have a greater hematogenous metastatic propensity.

Aged

Postoperative hepatitis status as a significant risk factor for recurrence in cirrhotic patients with small hepatocellular carcinoma.

BACKGROUND: Recurrence of small hepatocellular carcinoma (HCC) is common. Recent studies have suggested that the status of the underlying liver parenchyma is a significant risk factor for recurrence of HCC. METHODS: The postoperative values of transaminase were examined every 6 months after surgery in 57 patients with a surgically resected solitary small HCC measuring up to 3 cm in greatest dimension. Based on the patterns of the transaminase values, the patients were divided into two groups. Group 1 (n = 20) had a high transaminase level; the values of postoperative transaminase were always more than 100 IU/L. Group II (n = 37) had a low transaminase level; the values of postoperative transaminase were sometimes lower than 100 IU/L. RESULTS: The cumulative carcinoma-free survival rates in Groups I and II were 91% and 80%, respectively, at 1 year, 64.5% and 5.5%, respectively, at 3 years, and 48.2% and 0%, respectively, at 5 years after surgery. The disease free survival rates in Group I were significantly lower than those in Group II (P = 0.0007), although no significant differences in histologic risk factors for recurrence or in clinical backgrounds were observed. With regard to the recurrence pattern, solitary recurrence was more frequently observed in Group I (P = 0.02), compared with the patients in Group II. A histologic comparison between the primary and recurrent tumor in patients who underwent re-resection for solitary recurrence demonstrated the possible multicentric occurrence of HCC in 2 of 8 patients (25%) in Group I. CONCLUSIONS: This study suggests that the hepatitis status of the remnant liver plays an important role in the recurrence rates and patterns of small HCC after hepatectomy.

Carcinoma, Hepatocellular

Biologic characteristics of esophageal epithelial dysplasia assessed by proliferating cell nuclear antigen.

BACKGROUND: Proliferating cell nuclear antigen (PCNA) correlates with the cell proliferative state. Using a PCNA specific monoclonal antibody, various malignant neoplasms have been assessed for cell proliferation and malignant potential. However, there are few studies regarding the expression of PCNA in esophageal dysplasia. METHODS: PCNA expression was immunohistochemically determined in resected specimens from 27 patients with superficial esophageal carcinoma that contained areas with various degrees of dysplasia, carcinoma in situ (CIS), and carcinoma invading the mucosal layer. The authors estimated the cell proliferative activity and biologic characteristics of the basal and parabasal cells of these esophageal epithelial disorders. RESULTS: The degrees of PCNA labeling index (PCNA LI) of the basal layers were lower than those of the parabasal layers in normal epithelium and dysplastic lesions, respectively, whereas no difference in CIS was recognized between the two layers. The proportion of PCNA LI in the basal layer of moderate dysplasia was lower than that in the basal layer of severe dysplasia. Conversely, there were no statistical differences between severe dysplasia and CIS in both basal and parabasal layers. In terms of lymphocytic infiltration beneath the dysplasia, there was a close relationship between the degree of lymphocytic infiltration and the PCNA index of the basal and parabasal layers. CONCLUSIONS: PCNA expression may be a useful marker to reflect the biologic characteristics of esophageal dysplasia, suggesting that a high grade of dysplasia is as serious a lesion as esophageal carcinoma.

Biomarkers

Postoperative chemotherapy for colorectal cancer by combining 5-fluorouracil infusion and 1-hexylcarbamoyl-5-fluorouracil administration after curative resection.

BACKGROUND: Colorectal cancer is one of the major malignant diseases and, recently, its incidence appears to be increasing. Surgical resectability is an important prognostic determinant; however, recurrent tumors are commonly noted, even after apparently curative surgery. Because such metastatic disease cannot be cured, better adjuvant therapies are urgently called for. METHODS: We studied the effect of postoperative chemotherapy using 5-fluorouracil (5-FU) infusions and 1-hexylcarbamoyl-5-fluorouracil (HCFU) oral administration for curatively resected Stage II to IV colorectal cancer. This study was prospectively randomized and controlled and 251 (93.3%) of 269 patients were determined to be candidates for statistical assessment. The inductive regimen for Group A included a total of 6 5-FU intravenous injections, 10 mg/kg, on postoperative days 0, 1, 2, 7, 8, and 9. For maintenance therapy, Group A also received oral HCFU, 300 mg daily for 52 weeks beginning 2 weeks after surgery. The regimen for Group B included only 5-FU injections of Group A. RESULTS: There were no differences in the prognostic factors or doses of 5-FU between Groups A and B. In addition, no difference was observed in the toxicity rate between the two groups. Group A, with 5-FU infusions plus oral HCFU administration, produced a reduction in the recurrence rate and a prolongation of the survival time for patients with rectal cancer. In a retrospective analysis, this protocol was also effective for patients with Stage III to IV, wall invasion-positive, and lymph node metastasis-positive colorectal cancers. CONCLUSIONS: This study suggests that the combination of 5-FU infusions and the continuous oral administration of HCFU is a reasonable therapeutic approach for patients with surgically resected colorectal cancer and a high risk of recurrence.

Adult

Spindle cell hepatocellular carcinoma. A clinicopathologic and immunohistochemical analysis of 15 cases.

BACKGROUND: Spindle cell hepatocellular carcinoma (SpHCC) has rarely been reported, and its clinicopathologic characteristics, histogenesis, and prognosis after hepatic resection have yet to be clarified. METHODS: Fifteen cases of SpHCC, including 13 surgically resected patients and 2 autopsy cases, were studied clinicopathologically and immunohistochemically. RESULTS: In 13 resected patients, all except 1 were male and the serum alpha-fetoprotein (AFP) was positive in 6 (46%). Portal venous invasion and intrahepatic metastases were frequent. In an immunohistochemical analysis of 13 SpHCC tumors, cytokeratin CAM 5.2 and AFP were positive in 8 (62%) tumors and 3 (23%) tumors in both ordinary HCC and spindle cell components, respectively. The spindle cell components, but not ordinary HCC components, revealed a positive reaction for vimentin in 8 (62%) tumors, S-100 protein and HAM-56 in 3 (23%) tumors, HHF-35 in 2 (15%) tumors, and alpha-smooth muscle actin, desmin, and KP-1 in 1 (8%) tumor, respectively. p53 overexpression was found in two SpHCC tumors. The survival curve after hepatic resection in the 13 patients with SpHCC was significantly worse than that of the 371 patients with Stage II-IV ordinary HCC (P < 0.001). CONCLUSIONS: These results suggest that SpHCC represents a sarcomatous transformation of HCC. The spindle cell components revealed an immunohistochemical expression of several markers of mesenchymal cells. In addition, poor survival after hepatic resection was documented.

Adult

Results of 280 liver resections for hepatocellular carcinoma.

OBJECTIVE: To evaluate the recent results of liver resection in patients with hepatocellular carcinoma. DESIGN: Retrospective study. SETTING: A university hospital in Japan. PATIENTS: Two hundred eighty patients who underwent liver resection with complete extirpation of hepatocellular carcinoma from 1985 to 1993. MAIN OUTCOME MEASURES: Morbidity and survival after operation and the pathologic features of hepatocellular carcinoma according to the TNM classification of the International Union Against Cancer. RESULTS: More than 40% of the patients with stages I and II disease underwent a partial resection of the liver, whereas 50% of those with stages III and IVA were operated on with more than a bisegmentectomy. Fifty percent of all patients had no postoperative complications. The morbidities included intra-abdominal abscess (7%), bile leakage (5%), and hepatic failure (4%, of whom half died; mortality rate, 2%). Histopathologically, 32% of the stage I tumors were well differentiated (grade 1), while, in stage III, 56% had portal invasion and 61% had daughter lesions in the liver. The cumulative survival rates of patients with stages I, II, and III disease and all patients at 5 years were 69%, 52%, 32%, and 50%, respectively, while the disease-free survival rates at 5 years were 38%, 34%, 17%, and 29%, respectively. CONCLUSION: The recent results of liver resection for hepatocellular carcinoma are generally satisfactory; however, the recurrence rate is still high.

Aged

Simplified inflow control using stapling devices for major hepatic resection.

We describe the efficacy of a new technique for hepatic inflow division using stapling devices in major hepatic resections. We studied 28 consecutive patients who underwent major hepatic resection at a tertiary referral center by en masse inflow control of Glisson's pedicle in 1993 and 1994, of whom 10 underwent inflow control with stapling devices. Although stapling devices were used for larger tumors (mean +/- SD, 12.2 +/- 8.6 vs 5.7 +/- 5.0 cm; P = .02), the operation time (261 +/- 57 vs 301 +/- 143 minutes), operative blood loss (2071 +/- 1318 vs 4792 +/- 6586 mL), postoperative intra-abdominal bleeding (0% [0/10] vs 17% [3/18]), and hospital stay (16.0 +/- 2.6 vs 20.6 +/- 7.4 days) were favorable for resections with staplers vs resections without staplers; the overall incidences of postoperative complications (40% [4/10] vs 39% [7/18]) and hospital death (10% [1/10] vs 6% [1/18]) were comparable in the two groups. We conclude that stapling devices allow simple, quick, and safe en masse inflow control in major hepatic resections.

Aged

Postoperative complications after pneumonectomy for treatment of lung cancer: multivariate analysis.

The charts of 62 patients with primary lung cancer who underwent a pneumonectomy at our department from 1979 through 1992 were reviewed for the evaluation of postoperative morbidity and mortality. The 30-day mortality was 3/62 or 4.8%. Postoperative complication occurred in 37 of 62 patients (60%). The most common complication was a supraventricular tachyarrythmia. A major complication, which was defined as one necessitating re-thoracotomy or one which caused death, occurred in 19 patients (31%). We analyzed 43 perioperative variables for their predictive value of postoperative morbidity and mortality. Univariate analysis indicated that an elevated serum LDH, low predicted forced vital capacity, low predicted forced expiratory volume in 1 sec (FEV1) were significantly associated with the occurrence of a major complication. A multivariate logistic regression model indicated that a high LDH level, a low predicted FEV1 and no extubation following surgery were associated independently with a postoperative major complication. Since only the complete removal of a tumor offers a chance for cure for the treatment of non-small cell lung cancer, it is sometimes necessary to perform a pneumonectomy for these high-risk patients. Patients identified as being at high risk of a major complication should be candidates for intensive preoperative evaluation and perioperative care.

Adult

Postoperative recurrence of solitary small hepatocellular carcinoma.

The prognosis of hepatocellular carcinoma after hepatic resection remains poor. The major cause is postoperative recurrence, most frequently intrahepatic. During the past 7 years, we conducted a detailed study of recurrence after hepatectomy in 34 patients with solitary small hepatocellular carcinoma measuring no larger than 4 cm in diameter, in which 13 cases had postoperative recurrent tumors, and two cases were considered multicentric. Eighty-five percent of recurrences were diagnosed at 6-18 months after the operation. The cumulative recurrence rates were 61% at 5 years after operation. When analyzing the factors affecting recurrence, a significant difference was observed regarding tumor diameter. After recurrence, most patients underwent percutaneous ethanol injection treatment and/or transcatheter arterial chemoembolization and lipiodolization. Four patients died of progressive disease within 1 year after recurrence; the treatment thus seemed to have no effect. The other patients with recurrence remain alive with the disease. The overall cumulative survival rates in this series were 76% at 3 years and 60% at 5 years after operation. To obtain better results after hepatectomy, even for small hepatocellular carcinoma, careful, long-term follow-up evaluation is therefore necessary for the multidisciplinary treatment of the postoperative recurrence, as well as the early diagnosis of tumors in high-risk patients.

Adult

Immunohistochemical expression of sialyl Tn, sialyl Lewis a, sialyl Lewis a-b-, and sialyl Lewis x in primary tumor and metastatic lymph nodes in human gastric cancer.

Sialyl Lewis Tn(STN), sialyl Lewis a(CA-9-9), sialyl Lewis a-b-(DU-PAN-2), and sialyl Lewis x(SLX) antigens were immunohistochemically examined in the primary tumor and metastatic lymph nodes in 35 patients with advanced gastric cancer. STN, CA-19-9, DU-PAN-2, and SLX were expressed in 91%, 60%, 31%, and 60% in the primary lesion, and 77%, 54%, 22%, and 51% in the metastatic lesion, respectively. In only four cases, (11%) were all four antigens expressed in both the primary and metastatic lesions. Three antigens were expressed in 49% of primary lesions and in 20% of metastatic lesions. Compared with expression in primary lesions, increased, unchanged and decreased expressions in metastatic lesions were noted in 23%, 37%, and 40% for STN, 20%, 40%, and 40% for CA-19-9, 17%, 57%, and 26% for DU-PAN-2, and 26%, 31%, and 43% for SLX, respectively. These results indicate that the tumor in the primary and metastatic lesions has a heterogeneous expression of sialyl-related antigens. However, metastases cannot be predicted based upon the expression of these antigens.

Adult