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Biomedical subjects

S Adachi

Publications and source records attributed to S Adachi.

535 records · Page 30Linked to original sources

A phase I study of cisplatin i.p. and carboplatin i.v. with G-CSF in patients with ovarian cancer.

We conducted a dose-escalation study with a fixed dose of intraperitoneal cisplatin and G-CSF support of carboplatin using the Calvert formula in epithelial ovarian cancer. Twenty-five patients were entered in this study. On day 1, carboplatin was administered intravenously at target AUCs of 4, 5, 6, and 7. On day 2, cisplatin was given i.p. in 70 mg/m2. G-CSF, 50 microgram/m2, was administered subcutaneously from day 7 to 16. Cycles were scheduled to be delivered every four weeks. A total of 85 cycles were administered. The maximum tolerated dose was AUC 7 mg/ml x min of carboplatin. The overall response rate was 80% (12/15). The combination in this regimen is feasible, and a phase II study of this regimen is warranted.

Adult↗

Benefits of combining radiotherapy with aggressive resection for stage IV gallbladder cancer.

BACKGROUND/AIMS: The efficacy of combining resection and radiation in the management of advanced gallbladder cancer has not yet been defined. In this study, effects of combining radiation therapy on survival, local control and the pattern of recurrences were analyzed as a retrospective review. METHODOLOGY: From October 1976 to May 1996, 85 patients with stage IV (pTNM) gallbladder cancer underwent various aggressive resection modalities in our institute, including 34 liver resections, 30 hepatopancreaticoduodenectomies. Intra-operative, external or intracavitary radiation therapy was supplemented to resection in 47 patients. RESULTS: The 30-day operative mortality rate was 5.9% and the overall 5-year survival rate of stage IV disease patients was 6.3%; 3 patients are living well more than 6 years after surgery. Adjuvant radiotherapy yielded a significantly (p=0.0023) higher 5-year survival rate (8.9%) than resection alone (2.9%). The local control rate was significantly (p=0.0467) higher in the adjuvant radiation group than in the resection alone group (59.1% vs. 36.1%). However, there was no statistical difference in the frequency of distant metastasis between the two groups. Significant improvement (p=0.0028) of long-term survival was exhibited when radiation was used appropriately on patients with microscopic residues only. Those with macroscopic or without microscopic residues failed to improve. The 5-year survival rate and median survival time of patients receiving adjuvant radiation therapy for microscopic residues were 17.2% and 463 days, respectively. CONCLUSIONS: Adjuvant radiation therapy following aggressive resection, in certain circumstances, improves prognosis with acceptable operative mortality for stage IV gallbladder cancer.

Adenocarcinoma↗

Correlation of chemosensitivity to anticancer drugs and telomere length, telomerase activity and telomerase RNA expression in human ovarian cancer cells.

BACKGROUND: We examined the correlations among telomere length (TRF), telomerase activity (TA) and the steady-state level of telomerase RNA expression (hTR) of human ovarian cancer cells with different phenotypes and investigated whether the cells' sensitivities to anticancer agents correlate with TRF, TA or hTR. MATERIALS AND METHODS: The TRF, TA and hTR of 11 human ovarian cancer cell lines and 2 cisplatin-resistant ovarian cancer cell lines were determined by genomic Southern blotting, a telomeric repeat amplification protocol and reverse transcription-polymerase chain reaction. The chemosensitivities of the cell lines to cisplatin (CDDP), paclitaxel (TAX), etoposide (ETO), CPT-11 (CPT), cyclophosphamide (CYC), ifomide (IFO) and doxorubicin (DOX) were decided as IC50 values by calorimetric assay. RESULTS: All 11 cell lines presented shorter mean TRFs (5.0 kb) than normal control tissue (8.0 kb); 10 cell lines presented a 3.2-fold higher mean TA than the control and all 11 cell lines expressed hTR. Quantitatively, the steady-state levels of hTR correlated with the TRF (p < 0.05). Significant positive correlations between hTR and CDDP sensitivities (at 24 hours of exposure), ETO (72 hours), CPT (48 hours) and CYC/IFO (24-72 hours) were observed. The same was true for TRF and the CDDP sensitivities (at 24 hours). TAX and DOX did not have any impact on these factors. The TRF, TA and hTR values in the two CDDP-resistant cell lines were generally reduced, compared to their parent cell lines. CONCLUSIONS: Alkylating agents (CDDP, CYC and IFO) and topoisomerase inhibitors (ETO, CPT) may have the potential to influence the structural alteration of hTRs and telomeres and thus, the down-regulation of the TA in ovarian cancer cells.

Antineoplastic Agents↗

Prognostic results of cisplatin IP and carboplatin IV with G-CSF in patients with ovarian cancer.

We performed a dose-escalation study of carboplatin combined with a fixed dose of intraperitoneal cisplatin and G-CSF in patients with epithelial ovarian cancer, and analyzed the progression-free and overall survival. Six of the patients who entered the study with stage IC and II disease are still alive with no evidence of disease. The five-year survival rate was 61% for the 18 patients with stage III and IV disease; progression-free survival over 5 years was 32%. Our results show this to be an effective treatment regimen for epithelial ovarian cancer. Prognosis is good with this combined carboplatin/cisplatin/G-CSF therapy, especially for those patients with microscopic or no residual disease.

Adenocarcinoma↗

A pilot study of paclitaxel and carboplatin for recurrent ovarian cancer.

Combination chemotherapy with paclitaxel and platinum is the most effective regimen for advanced ovarian cancer. Second-line chemotherapy with paclitaxel (135 mg/m2, 24 h) and carboplatin (AUC 5-6) is also effective for patients who relapse on the same regimen after 6 months or more. However, it has been shown that the same efficacy and less myelosuppression can be achieved with a 3-h infusion of paclitaxel (135 mg/m2), and that dose intensification of carboplatin to an AUC values larger than 4-6 is meaningless. Therefore, we decided to conduct a pilot study of paclitaxel (135 mg/m2, 3 h) and carboplatin (AUC 4-5) for ovarian cancer patients who had relapsed or were resistant to a platinum-containing regimen without paclitaxel. Eligibility criteria included patients with relapsed or resistant ovarian cancer (no specified duration from prior therapy), age 16-75 years, with performance status 0-2, and adequate bone marrow, renal, and hepatic function. Paclitaxel was administered at a fixed dose of 135 mg/m2 followed by one of two carboplatin doses (AUC 4 or 5). Specific doses were alternated between individual patients by the order in which they entered the study. Treatment was repeated every 3 weeks, and more than 4 cycles were administered. A total of 11 patients were enrolled. Carboplatin was administered to 6 patients at an AUC of 4 and to 5 patients at an AUC of 5. The age of patients ranged from 18 to 65 years (median: 54). Other patient data (number of patients): serous (8), non serous (3), patients with measurable disease (9), assessable/CA 125 (3), study drug administration less than 6 months after prior therapy (5), study drug administration 6 months or more after prior therapy (6). Response was defined by CT and CA 125 level. CR was observed in 25% (2/8), PR in 38% (3/8), NC in 25% (2/8), and PD in 13% (1/8) of the patients. The response rate with assessable patients was 100% (3/3), and the overall response rate was 73% (8/11). Two patients with grade 1 tachycardia and grade 4 thrombocytopenia, respectively, refused further treatment after 2 cycles. No other patients experienced grade 4 hematologic toxicity or grade 3 non-hematologic toxicity. The median survival duration after paclitaxel and carboplatin therapy was 21+ months (6-26+ months). This regimen is easy to manage in heavily pretreated patients and seems to have good efficacy. To further assess the efficacy, a phase II study is needed.

Adenocarcinoma↗

Hepatic resection for metastatic tumors from noncolorectal carcinoma.

BACKGROUND/AIMS: The role of liver resection for hepatic metastases from noncolorectal carcinomas has yet to be clarified. The present study examines a single institutional experience of hepatic resection for noncolorectal metastases. METHODOLOGY: From January 1987 to March 1999, 14 patients underwent curative resection for liver metastases from noncolorectal carcinomas. Records of these patients were reviewed. RESULTS: Resections were performed for liver metastases from gastric cancers (n = 8), pancreatic cancers (n = 2), and cancers of bile duct, the papilla of Vater, kidney, and breast (n = 1, each). Six patients (5 with gastric cancers and 1 with pancreas cancer) presented with synchronous disease and 8 with metachronous disease. In the gastric cancer patients, there are 2 disease-free survivors (26 and 53 months) in the metachronous group, though all of the 5 patients with synchronous disease died within 29 months. All of the 4 patients with pancreatobiliary carcinomas died within 2 years. One case of breast cancer and another of renal cell cancer are alive without disease at 49 and 9 months, respectively. CONCLUSIONS: For metastases from gastric cancers, better survival after hepatic resection is expected in metachronous cases than in synchronous cases. Hepatic resection may afford little benefit for patients with liver metastases from pancretobiliary cancers.

Aged↗

Retroperitoneal multiple lymphangioma with differential cyst contents causing hydronephrosis and biliary dilatation.

We report a 40-year-old woman with retroperitoneal multiple cystic lymphangioma. Multiple cystic lesions were found on both sides of the aorta in the retroperitoneal and right pelvic spaces. These thin-walled cysts gradually increased in size leading to left hydronephrosis and dilatation of the common bile duct with cholecystitis, requiring resection. Analysis of cystic contents revealed differences between the cysts. The right cyst contained high concentrations of amylase, 3429 U/L, while the left cyst contained high concentrations of triglyceride, 470 mg/dL. No reports of patients with idiopathic retroperitoneal cystic lymphangioma have described differences in cystic contents. Differences in cystic contents according to tumor location strongly suggest that the cause of retroperitoneal lymphangioma is a developmental malformation in which lymphangiectasia follows the failure of developing lymphatic tissue to establish normal communication with the remainder of the lymphatic system.

Adult↗

Bone morphogenetic protein-2 and type IV collagen expression in psammoma body forming ovarian cancer.

Psammoma bodies (PBs), characterized as calco-spherules with concentric laminations, are common in serous tumors of the ovary. However, there is no agreements as to how the PBs are formed. Bone morphogenetic protein-2 (BMP-2) has recently been proposed to be involved in the calcification of tumor cells and recent electron microscopic studies demonstrated the presence of type IV collagen in PBs. Based on this evidence, we postulated a possibe role for BMP-2 and type IV collagen in the formation of PBs in ovarian cancer. We examined the expression of BMP-2 and typle IV collagen by immunohistochemistry and reverse transcription PCR (RT-PCR) in PBs-forming (NK-211) and -non-forming (SHIN-3, KF-1, A2780, KK-92, KOC-2S, SKOV-3, OMC-3, MN-1, EC, and KEN-3) ovarian cancer cell lines in vitro and in surgical specimens of serous adenocarcinoma (SA) with/without PBs and mucinous adenocarcinoma (MA) of the ovary. Cellular growth of cell lines was also evaluated by their doubling time in vitro. Transcripts for BMP-2 mRNA were detected by RT-PCR in all cell lines. By immunohistochemistry, BMP-2 protein expression was positive in 45% (5 out of 11) of cell lines. 36.4% (4 out of 11) were positive for type IV collagen. PBs-forming NK-211 was intensively positive for both BMP-2 and type IV collagen. In addition, NK-211 demonstrated extremely slow growth with a doubling time of 450 hours. In surgical specimens, BMP-2 vs. type IV collagen positivities in tumor cells were 100% (20 out of 20) vs. 40% (8 out of 20) in SA with PBs, 61.1% (11 out of 18) vs. 0% (0 out of 18) in SA without PBs and 75% (9 out of 12) vs. 0% (0 out of 12) in MA. In PBs themselves, 100% (20 out of 20) positivity for BMP-2 and 80% (16 out of 20) for type IV collagen was shown. These results raise the possibility that BMP-2 and type IV collagen-producing slow growing tumor cells form PBs in ovarian cancer.

Bone Morphogenetic Protein 2↗

Preparation of peptide mixture with high Fischer ratio from protein hydrolysate by adsorption on activated carbon.

A peptide mixture with a high Fischer ratio (a molar ratio of Val + Leu + Ile to Phe + Tyr) was prepared by the adsorptive separation of a casein hydrolysate by activated carbon. The effects of the pH and ethanol content of the hydrolysate on the Fischer ratio and on the yield of the resulting peptide mixture were examined. A peptide mixture with the Fischer ratio of 31.6 was obtained at pH 2.5 without the addition of ethanol. The Fischer ratio was close to the ratio of the infusion solution of free amino acids that is now used for patients with liver diseases.

Adsorption↗

A radical operation for the Budd-Chiari syndrome associated with obstruction of the inferior vena cava. A report of six patients.

The Budd-Chiari syndrome is caused by an occlusion of the hepatic veins and is often associated with an obstruction in the hepatic portion of the inferior vena cava (IVC). Therefore, the various shunt operations done in an attempt to relieve the portal hypertension are often not effective. By using a radical surgical technique on six patients with Budd-Chiari syndrome, the liver was freed and a wide longitudinal incision was made in the hepatic portion of the IVC. The obstructed hepatic vein was reopened using a Fogarty catheter, and a pericardial patch reinforced with a Teflon prosthesis was secured over the incision. Two patients were still asymptomatic 3 and 4 years after operation. Two patients died postoperatively of pneumonia and hepatic insufficiency. The two other patients were discharged in fair condition, and one died 6 months postoperatively following hepatic failure.

Adult↗

Radiology of lung cancer.

It is of vital importance not only to prevent lung cancer but also to detect and treat it as early as possible. Plain chest X-ray examination often provides preliminary data useful for the early detection of lung cancer, and multiple diagnostic modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) are used to obtain more accurate information. The authors describe the clinical utility of imaging diagnosis by computed radiography (CR), advanced multiple beam equalization radiography (AMBER), CT, and MRI in term of the imaging-pathologic correlation. We would like to emphasize that these modalities are not competitive but supplementary. It should be anticipated that, as technological improvements continue to be made, each modality will assume an increasingly important role in the imaging of lung cancer.

Diagnostic Imaging↗