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Biomedical subjects

Toshiharu Furukawa

Publications and source records attributed to Toshiharu Furukawa.

At least 19 recordsLinked to original sources
PubMed2006

Operative indications for relatively small (2-5 cm) gastrointestinal stromal tumor of the stomach based on analysis of 60 operated cases.

BACKGROUND: Removal of the primary lesion with a clear operative margin is the standard treatment for gastrointestinal stromal tumor (GIST) of the stomach. However, there are few reports on the operative indications for relatively small GIST. METHODS: Clinicopathologic features and survival data of all 60 patients with GIST of the stomach treated at Keio University Hospital from 1993 to 2004 were analyzed. Laparoscopic wedge resection was used as the primary procedure for tumors between 2 to 5 cm. Tumors larger than 5 cm were resected by laparotomy or laparoscopy-assisted operation. RESULTS: Thirty-five lesions (58.3%) were resected by laparoscopic wedge resection, 3 by laparoscopic operation with a small skin incision and 22 by conventional open procedures. The mean size of the tumors was 42.5 mm, with a range of 18 to 150 mm and a median value of 35.5 mm. All operative margins were clear, but 1 patient had liver metastases at the time of resection of the primary lesion. The median follow-up period was 53 months and the 5-year disease-free survival rate (DFS) was 96.1%. No local recurrence or distant metastasis was encountered in patients with tumors smaller than 4 cm. A statistically significant correlation was observed between tumor size and mitotic count in this cohort (P = .010). Tumors from the intermediate- (n = 14) and high-risk (n = 10) groups as classified by the Risk Assessment Classification showed significantly worse DFS than the low-risk and very low risk group (n = 35) (89.9% vs 100% in 5-year DFS, P = .045). Even among tumors smaller than 3 cm, 2 of 14 cases (14.3%) were classified into the intermediate-risk group. CONCLUSIONS: Although a prospective randomized trial remains to be performed, this study provides additional evidence suggesting that the early removal of GIST, at 5 cm or less in size, provides better DFS than later removal of the tumor at a larger size.

Adult↗
PubMed2005

Gallstone disease after extended (D2) lymph node dissection for gastric cancer.

Few studies have reported the incidence and clinical outcomes of gallstone disease after extended (D2) lymph node dissection for gastric cancer. The present study was designed to retrospectively compare limited (D1) and D2 dissections in terms of gallstone formation, presentation of gallstones, and surgery for gallstone disease. A total of 805 Japanese gastric cancer patients (595 male, 210 female) who underwent curative resection with D1 (n = 490) or D2 (n = 315) dissection were retrospectively reviewed. Of those subjects followed for 70.5 +/- 44.3 months (range: 2-196 months), 102 (12.7%) developed gallstones. The incidence of gallstone formation was higher in the D2 group than in the D1 group (17.8% vs. 9.4%, p = 0.001). The interval between gastrectomy and detection of gallstones was shorter in the D2 group than in the Dl group (18.8 +/- 11.4 months vs. 29.4 +/- 18.3 months, p = 0.002). Of those with gallstones followed for 48.0 +/- 28.6 months (range: 1-158 months), 74 (72.5%) remained asymptomatic, and 15 (14.7%) experienced mild biliary pain. Thirteen patients (12.7%) developed recurrent biliary pain (n = 3) or biliary complications (n = 10; 6 acute cholecystitis, 3 obstructive jaundice, and 1 cholangitis), and required surgical treatment. Surgery was more frequently sought in the D2 group than in the D1 group (19.5% vs. 4.3%, p = 0.033). In conclusion, patients with D2 dissection developed gallstones more frequently and earlier than patients with D1 dissection. Of those with gallstones, patients with D2 dissection required surgery more often than patients with D1 dissection. A closer follow-up should be mandatory for gallstone disease after D2 dissection, but further studies are needed before generalizations can be made.

Aged↗
PubMed2005

Gastric cancer mimicking a submucosal tumor diagnosed by laparoscopic excision biopsy.

We report a case of advanced gastric cancer exhibiting the features of a submucosal tumor (SMT) of the gastric body. The patient was a 50-year-old male in whom a gastric SMT was detected during a mass screening examination. Upper gastrointestinal endoscopy revealed a protuberant tumor, 2 cm in diameter, covered with normal-appearing mucosa. Examination of an endoscopic biopsy specimen of the tumor revealed chronic gastritis with regenerative and erosive changes. An endoscopic ultrasound examination demonstrated a hypoechoic mass in the third layer of the gastric wall. The clinical diagnosis was gastric SMT, and the patient's course was monitored. Twenty-six months after the initial visit to our hospital, an endosonograph-guided biopsy revealed Group III (borderline lesion). Three months after the biopsy, the size of the SMT had increased slightly. Laparoscopic wedge resection of the tumor was performed to make a pathologic diagnosis and we were able to make a diagnosis of gastric lymphoepithelioma-like carcinoma intraoperatively. Gastrectomy with lymph node dissection was followed as curative surgery. Laparoscopic total excision biopsy is a useful technique in patients with a gastric SMT whose diagnosis has not been confirmed pathologically.

Biopsy↗
PubMed2004

Clinical and pathological disappearance of peritoneal dissemination in a patient with advanced gastric cancer receiving chemotherapy with S-1 and low-dose cisplatin.

A 54-year-old woman with severe abdominal distention suffered from massive ascites. Cytological examination revealed adenocarcinoma cells, leading to a diagnosis of peritonitis carcinomatosa. Gastrointestinal fiberscopy (GIF) resulted in a histological diagnosis of type 4 advanced gastric cancer with signet-ring cell carcinoma. The clinical diagnosis was confirmed to be cT3(SE)cN1cM0cH0cP1, cStage IV gastric cancer, type 4, according to the Japanese classification of gastric carcinoma. The patient was treated with S-1 and low-dose cisplatin (CDDP) in order to alleviate the critical state of the disease. After the third cycle of the regimen, the clinical response of P1 was classified as a partial response (PR) according to the World Health Organization (WHO) criteria. The patient's appetite loss and abdominal discomfort were markedly alleviated. The patient experienced grade 2 leukocytopenia throughout the regimen. Surgery was performed. Ascites and peritoneal disseminated lesions were not observed, and cytological examination of the peritoneal washes was negative. Total gastrectomy with D1 lymph node dissection was performed, and the surgical diagnosis was sT3(SE)sN0sM0sH0sP0; sStage II. Microscopically, viable cancer cells were found to be scattered throughout the subserosal-serosal layers in the resected stomach. All of the samples from lesions that were potentially cancers involving peritoneal dissemination were diagnosed as fibrous scar tissues without any viable cancer cells. The patient is alive without recurrence at 10 months after surgery and 14 months after the initial chemotherapy. Thus, systemic chemotherapy with S-1/low-dose CDDP achieved desirable control of peritoneal disseminated cells, as assessed microscopically, suggesting that the regimen may be an effective strategy for the treatment of advanced gastric cancer with peritonitis carcinomatosa.

Ascites↗
PubMed2003

Chemosensitivity testing--present and future in Japan.

Radical surgery with extended lymph node dissection is the first and only curative treatment of gastrointestinal cancer. Although the combined cancer chemotherapy has achieved 30%-50% response rates, a controversy still remains over the significance of the adjuvant cancer chemotherapy after surgery. To break through this limitation, we have introduced the chemosensitivity test to evaluate the appropriate adjuvant cancer chemotherapy for advanced gastrointestinal cancer. Our plural studies indicated that the chemosensitivity test would be useful in evaluating the appropriated adjuvant chemotherapy by increasing survival in the sensitive group. Recently, the molecular targets have been clarified for the conventionally available antitumor agents, e.g., thymidylate synthetase for 5-fluorouracil, ATP-binding cassette transporters for anthracyclines, glutathione-related detoxification for platins, and topoisomerase I for CPT-11, which will be applied for dinical use in evaluating the appropriate cancer chemotherapy. The chemosensitivity test is approved as "advanced clinical medicine" by the Japanese Ministry of Health, Welfare, and Labor in five institutes at present. Because complete dissection and chemosensitivity test-guided adjuvant chemotherapy will result in a survival benefit for patients with advanced gastrointestinal cancer, this test should be approved as "social insurance" for further wide clinical application.

Antineoplastic Agents↗
PubMed2003

Gastric carcinoid tumors with aggressive lymphovascular invasion and lymph node metastasis.

We report a patient with multiple gastric carcinoid tumors without hypergastrinemia. An abdominal computed tomography (CT) scan was performed in a 66-year-old Japanese man who had abdominal discomfort. An abnormal, round, 2.5 cm mass close to the lesser curvature of the stomach was detected. Multiple small gastric carcinoid tumors were also detected by endoscopy. A total gastrectomy with lymph node dissection was performed after it was determined that the round mass was a lymph node metastasis of carcinoid tumor. Further pathological investigation of the surgical specimen revealed multiple gastric carcinoid tumors with severe lymphovascular invasion. The carcinoid tumors in the present patient were not related to hypergastrinemia. These lesions could not be grouped as any of the three types of gastric carcinoid tumors in the recent classification. Furthermore, as a simple distal gastrectomy is the standard treatment for multiple carcinoid tumors of the stomach, we recommend that a precise histopathological evaluation should be performed before an appropriate curative surgical treatment is selected.

Abdominal Pain↗
PubMed2003

Reduced angiogenesis in peritoneal dissemination of gastric cancer through gelatinase inhibition.

Marimastat is a broad-spectrum matrix metalloproteinase (MMP) inhibitor that inhibits almost all major MMPs, key enzymes in gastric cancer invasion and metastasis. We investigated the ability of marimastat to inhibit tumor angiogenesis in the severe combined immuno-deficient (SCID) mouse/human gastric cancer model of peritoneal dissemination. A human stomach adenocarcinoma cell line, TMK-1, was injected intraperitoneally into SCID mice. On the 7th day after tumor inoculation, the administration of marimastat (27 mg/kg/day) was initiated and the treatment was continued for 2 weeks using subcutaneously-inoculating mini-osmotic pumps. On the 21st day, the mice were killed and the disseminated nodules were evaluated. Total weights, numbers, and the microvascular density of the disseminating nodules were significantly lower in mice treated with marimastat compared to the control group. Film in situ zymography demonstrated that net gelatinolytic activity in the tissues was weaker in treated-group nodules than in control-group nodules. Thus, our results suggested that marimastat inhibited peritoneal dissemination of human gastric cancer cells through inhibition of tumor angiogenesis, possibly involving the down-regulation of gelatinases, in SCID mice injected with human gastric cancer cells.

Animals↗
PubMed2003

Cystic partially differentiated nephroblastoma, embryonal rhabdomyosarcoma, and multiple congenital anomalies associated with variegated mosaic aneuploidy and premature centromere division: a case report.

A rare association of embryonal genitourinary tumor(s) with cerebral malformations has been reported in eight infants with variegated mosaic aneuploidy (VMA) and premature centromere division. The authors report a new case of cystic partially differentiated nephroblastoma and embryonal rhabdomyosarcoma associated with VMA, premature centromere division, microcephalus, Dandy-Walker malformation, and cataracts. Nonrandom involvement of the chromosomes was found in VMA of the lymphocytes and the skin fibroblasts. In the cultured nephroblastoma cells, hyperdiploidy involving the same group of chromosomes involved in VMA of the somatic cells was observed, suggesting their derivation from the aneuploid population of the somatic cells.

Abnormalities, Multiple↗
PubMed2003

Possible chemoresistance-related genes for gastric cancer detected by cDNA microarray.

To identify chemoresistance-related genes of gastric cancer, we utilized cDNA microarray technology. Thirty-five gastric cancer specimens surgically resected at our institute between 1998 and 1999 were studied for quantification of expression of 6300 genes by means of oligonucleotide microarray methods, and the results were evaluated in comparison with the chemoresistance of the specimens, which was determined by MTT (tetrazolium-based 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Inhibition rates (IR) were determined for cisplatin (DDP), 5-fluorouracil (5-FU), mitomycin C or doxorubicin. IR of 60% or more was regarded as sensitive to each agent, and IR of less than 40% was defined as resistant. Clustering was successfully completed for DDP, resulting in selection of 23 candidates as DDP-resistance-related genes, including vascular permeability factor, 2 membrane transporting subunits, and retinoblastoma-binding protein-1. In addition, further selection of DDP-resistance-related genes was performed according to these criteria: 1) Expression of the gene can be detected in more than 70% of resistant tumors. 2) Expression can be detected in less than 30% of sensitive tumors. 3) Expression in tumors is more than twice that of normal mucosa in more than 50% of specimens. Then, metallothionein-IG and heparin-binding epidermal growth factor-like growth factor (HB-EGF) were identified as candidate DDP-resistance-related genes. When known DDP-resistance-related genes were analyzed according to the MTT assay result, families of glutathione-S-transferase and cyclooxygenase-2 genes were also evaluated as resistance-related genes. For 5-FU resistance, dihydropyrimidine dehydrogenase and HB-EGF-like growth factor genes were also suggested to be resistance-related genes. The present study demonstrated that oligonucleotide microarrays can provide information regarding chemoresistance factors in cancer.

Antineoplastic Agents↗
PubMed2003

[Reporting of patient deaths and grave injury incidental to clinical practice].

The Japan Surgical Society has developed guidelines for the reporting of patient deaths and grave injury incidentally occurring in their clinical courses, following its declaration in March 2001 in reference to practitioners' duty to notify the police under Article 21 of the Medical Act. These guidelines can be summarized into three points. First, they are ethical guidelines for practitioners and are not concerned with the legal duty required under the Medical Act. Second, they require reporting of patient deaths even if the cause is still not confirmed as medical malpractice, and reporting of grave injury due to apparent medical malpractice, not mention deaths due to apparent medical malpractice. Third, it is emphasized that the guidelines be applicable for the time being until some generalized system is established, which is specialized to accept reports about patient deaths and grave injury incidentally occurring in their clinical course from every hospital nationwide and to collect data concerning small incidents and risks in medical practice. The Japan Surgical Society strongly requests that such a general system start to function as soon as possible. In advance, the current guidelines should be amended repeatedly in reference to problems occurring in actual cases.

General Surgery↗
PubMed2003

[Standardization of cancer treatment and legal medical standards].

Legal medical standards are usually applied in two ways in Japanese medical malpractice cases. One application is a judgment on the quality of medical treatment, and the other is an evaluation of the validity of informed consent. Legal medical standards are not equivalent in all medical institutions. If physicians in a medical institution are expected to be aware of the most recent medical knowledge, that becomes the medical standard of the institution. For physicians in major metropolitan medical institutions, such knowledge constitutes the medical standard even before it is published in the guidelines of a committee of an established national medicoprofessional society. The standardization of cancer treatment may be used as evidence in medical malpractice suits brought by cancer patients based on both the quality of treatment and valid informed consent. In addition, it is possible that the validity of informed consent may be given more weight by the courts than the following of a course of standardized treatment by individual physicians/medical institutions in cases where patients have done extensive research on and exhibit informed knowledge of new treatment modalities.

Humans↗