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Tetsuro Kubota

Publications and source records attributed to Tetsuro Kubota.

At least 19 recordsLinked to original sources
PubMed2006

Interim results of sentinel node biopsy during laparoscopic gastrectomy: possible role in function-preserving surgery for early cancer.

INTRODUCTION: Intraoperative detection of sentinel nodes (SNs) has been used clinically to predict regional lymph node (LN) metastasis in patients with breast cancer and malignant melanoma. Intraoperative lymphatic mapping and SN biopsy can potentially be combined with minimally invasive surgery. However, few reports have demonstrated the validity of SN biopsy during laparoscopic gastrectomy. The aim of this study was to investigate the feasibility and accuracy of laparoscopic lymphatic mapping in predicting LN status in patients with gastric cancer. METHODS: A total of 35 patients with gastric cancer diagnosed preoperatively as T1, N0 were enrolled. Endoscopic injection of technetium-99m-radiolabeled tin colloid was completed 16 hours before surgery, and radioactive SNs were identified with a gamma probe intraoperatively. Isosulfan blue dye was injected endoscopically during the operation. Laparoscopy-assisted gastrectomy with LN dissection was performed. All resected LNs were evaluated by routine pathology examination. RESULTS: SNs were detected in 33 (94.3%) of 35 patients. The mean number of SNs was 3.9, and the diagnostic accuracy according to SN status was 97.0% (32/33), as one patient with a false-negative result was observed. The patient with the false-negative specimen was finally diagnosed as having advanced gastric cancer with invasion into the proper muscular layer and severe lymphatic vessel invasion, causing destruction of normal lymphatic flow by the tumor. CONCLUSIONS: Radio-guided SN mapping during laparoscopic gastrectomy is an accurate diagnostic tool for detecting lymph node metastasis in patients with early-stage gastric cancer. Validation of this method requires further studies on technical issues, including indications, tracers, methods of lymph node retrieval, and diagnostic modalities of metastasis.

Adult↗
PubMed2006

Metastatic gastric cancer from malignant fibrous histiocytoma: report of a case.

Metastatic gastric cancer originating from malignant fibrous histiocytoma (MFH) is rare. To our knowledge, only nine other cases have been reported. We report the case of a 75-year-old man who underwent a distal gastrectomy for advanced gastric carcinoma, 2 years after resection of an MFH from the left side of his back. We based our preliminary diagnosis of primary advanced gastric carcinoma on the results of a preoperative biopsy specimen, which suggested either poorly differentiated adenocarcinoma or nonepithelial cell-originating malignant disease-like lymphoma. The resected stomach contained a large ulcerative tumor in the antral section, which was positive for Kp-1 and S-100 by immunohistochemical staining, confirming a pathological diagnosis of metastatic MFH of the stomach. He died of recurrence in the mediastinal space 16 months after the gastrectomy. Our analysis of this and previous cases suggests that resection may be inappropriate for patients with gastric metastasis of MFH because of the extremely high malignant potential of this tumor.

Aged↗
PubMed2006

Chemotherapy sensitivity and resistance testing: to be "standard" or to be individualized, that is the question.

Radical surgery with extended lymph-node dissection is the treatment of first choice and the only curative treatment for locally advanced gastric cancer. While recent combination chemotherapy with S-1 (a combination of tegafur with two biomodulators, gimeracil and oteracil) has achieved high response rates, controversy still remains regarding the significance of adjuvant cancer chemotherapy after surgery. We have been applying chemosensitivity testing in evaluating the appropriate adjuvant cancer chemotherapy for advanced gastric cancer. Our multiple studies have indicated that this chemosensitivity testing would be useful to improve the results of adjuvant chemotherapy, by increasing survivals in the sensitive group. The chemosensitivity testing is approved as "advanced clinical medicine" by the Japanese Ministry of Health, Welfare, and Labor at 11 institutes at present. While complete lymph-node dissection and chemosensitivity test-guided adjuvant chemotherapy has been reported to result in a survival benefit for patients with advanced gastrointestinal cancer, the clinical utility of the testing should be established by means of prospective, randomized clinical trials. Two pivotal clinical trials have been initiated to clarify the utility of chemosensitivity testing in the selection of the appropriate adjuvant cancer chemotherapy for gastric cancer.

Antineoplastic Agents↗
PubMed2006

Gastrointestinal stromal tumor (GIST) and imatinib.

Imatinib mesylate is the first and only effective drug for the treatment of gastrointestinal stromal tumor at present. Mutated exon 11 of the KIT receptor is essential for the pathogenesis and response to imatinib mesylate of gastrointestinal stromal tumor; the efficacy rate (complete response+partial response) of imatinib mesylate is 53.8%, and the disease-control rate (complete response+partial response+stable disease) is 84%. Almost 90% of patients experienced non-hematological and hematological adverse effects, which were tolerable, in particular at a daily dose of 400 mg imatinib mesylate, which warranted response induction for half of the patients, and is the dose approved by Japanese medical insurance. Clinical trials suggest that an increased dose of imatinib mesylate would be beneficial, and that the interruption of imatinib treatment might result in disease progression even after a partial response. Tentative Japanese guidelines for the diagnosis and therapy of gastrointestinal stromal tumors are being prepared by the Gastrointestinal Stromal Tumor Committee of the Japan Society of Clinical Oncology, and are presented here for critical comments by colleagues.

Algorithms↗
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↗
PubMed2006

Antiangiogenic agent SU6668 suppresses the tumor growth of xenografted A-431 cells.

SU6668 is an antiangiogenic agent that acts as a tyrosine kinase inhibitor for the vascular endothelial growth factor (VEGF) receptor. We treated xenografted A-431, a human squamous cell carcinoma cell line, with SU6668 to investigate the efficacy of tumor dormant therapy using angiogenesis inhibitors for patients with squamous cell carcinoma. A-431 cells were transplanted into severe combined immunodeficient (SCID) mice. The treatment group was given SU6668 at a dose of 200 mg/kg orally twice a day for 3 weeks; the control group was given only the vehicle in the same manner and intervals. SU6668 suppressed tumor growth of A-431 cells in the xenograft model. Furthermore, tumor volume and the number of vessels were significantly reduced in the treatment group compared with those of the control. No significant differences in body weight were found between the treatment and control groups, and no toxic reactions occurred during the experiment. We concluded that this agent was safe, efficient and potentially useful for the treatment of patients with squamous cell carcinoma.

Angiogenesis Inhibitors↗
PubMed2006

Antitumor effect of combination of S-1 and docetaxel on the human breast cancer xenograft transplanted into SCID mice.

In vivo experiments were performed on breast cancer xenografts to examine whether the combination therapy with S-1, an oral dihydrouracil dehydrogenase (DPD) inhibitory fluoropyrimidine, plus docetaxel functions as an additive/synergistic modulator in tumor growth. The human breast cancer xenograft, MDA-MB-435SHM, was inoculated into SCID female mice. The tumor growth and thymidylate synthase (TS)/DPD activity of tumors treated with the agents were investigated. The T/C value (relative mean tumor weight of the treated group/relative tumor weight of the control group) of the group treated with docetaxel, S-1 and combination therapy were 45.3, 63.1 and 29.8%, respectively; suggesting the positive antitumor effects of the combination therapy in particular. In addition, significant down-regulation of DPD activity was also observed in the tumors treated with S-1, docetaxel and their combination. Down-regulation of the DPD activity of the tumors is also considered to be correlated with the antitumor effect of the treated groups, suggesting its influence on the synergistic effect of the combination therapy.

Animals↗
PubMed2006

[A recent trial of chemo-radiation with S-1 against gastric cancer].

A recent development of novel anticancer agents like S-1, CPT-11 or taxanes has improved a therapeutic outcome for advanced gastric cancer, while conventional anticancer agents showed less anticancer effect against gastric cancer. The present main drug in Japan is S-1, which is easily used for outpatient with a high efficacy rate and low toxicity, also shows better effect in combination with other anticancer drugs than S-1 alone. In the present article, we demonstrated significant meaning of additional radiation therapy with anticancer drugs like S-1. With novel anticancer drugs like S-1, we will expose a clinical advantage and appropriateness for chemo-radiation therapy against gastric cancer discussed in the present references according to chemo-radiation therapy. Although chemo-radiation therapy has been recognized as one of the standard therapies for gastric cancer in Western countries, radiation therapy was selected in Japan for palliation therapy of recurrent disease or a terminal cancer to improve patients' QOL. On the other hand, we demonstrated in our trial of chemo-radiation therapy with S-1/low-dose CDDP/radiation (TSLDR), which was applied to initial treatment against highly advanced Stage IV gastric cancer and revealed the usefulness of the regimen in anticancer effect and toxicity. In addition, chemo-radiation therapy including novel anticancer agents like S-1 will be discussed based on various kinds of view points, expecting a better clinical outcome of multimodal therapies against advanced gastric cancer.

Adult↗
PubMed2005

Recent advances in sentinel node navigation for gastric cancer: a paradigm shift of surgical management.

The sentinel node (SN) is defined as the first draining node from the primary lesion and it has proven to be a good indicator of the metastatic status of regional lymph nodes in solid tumors. In the past 5 years, the validity of SN concept for gastric cancer has been demonstrated by a number of single institutional studies. Using a dual tracer method as the optimal procedure, the radio-guided method allows us to confirm the complete harvest of SNs by gamma probing, while the dye procedure enables us to perform real time observation of the lymphatic vessels. From previous reports, clinically staged T1N0 gastric cancer seems to be a good entity on which to try to change the therapeutic approach based on SN biopsy. At present, two large scale prospective multicenter trials are on-going in Japan. To overcome some remaining issues, such as limited sensitivity of intra-operative diagnosis of metastasis, and technical difficulty in laparoscopic SN detection, further technical and instrumental developments will be required. During this transitional phase, focused lymph node dissection targeted to sentinel lymphatic basins and modified resection of the stomach is an acceptable approach. Although there are several remaining issues, SN navigation should provide a paradigm shift for the surgical management of early gastric cancer in near future.

Clinical Trials as Topic↗
PubMed2005

Morphologic analysis of gastroesophageal reflux diseases in patients after distal gastrectomy.

The precise mechanisms that cause gastroesophageal reflux after distal gastrectomy remain unclear. We analyzed the endoscopic findings of the cardia and the position of the remnant stomach, which are related to gastroesophageal reflux. We retrospectively examined the records of 45 patients with Billroth I (B-I) and 39 patients with Roux-en-Y (R-Y) procedure for gastric cancer. Esophagitis was evaluated by the Los Angeles (LA) classification. The endoscopic findings of hiatus hernia were classified according to the criteria of the Keio Cancer Detection Center form (K-form). The valvular appearance of the cardia was classified according to V-grades. The height of the remnant stomach was measured on computed tomography scans. The postoperative findings of esophagitis in the B-I group were significantly worse than the preoperative findings, but no significant change was observed in the R-Y group. The postoperative V-grades and K-forrn findings in the B-I group were worse than their preoperative findings. In the R-Y group, however, there was no significant change in the V-grades or K-form findings. In addition, the height of the remnant stomach was significantly higher in the B-I group than in the R-Y group. This study suggested that an aggravated cardia is associated with the B-I procedure and that the position of the remnant stomach may therefore play an important role in the occurrence of postoperative reflux esophagitis. In contrast, the R-Y operation was shown to preserve the cardia and the position of the remnant stomach better. As a result, R-Y might help prevent not only duodenogastric reflux but also gastroesophageal reflux.

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

Minimally invasive surgery for gastric cancer--toward a confluence of two major streams: a review.

The minimalization of therapeutic invasiveness in order to preserve quality of life (QOL) is a major topic in the management of early gastric cancer. After laparoscopic surgery for gastric cancer was introduced by Kitano et al. in 1991, an enthusiasm to develop laparoscopic procedures has grown steadily. In the initial phase, early gastric cancer limited to the mucosal layer with no risk of lymph node metastasis was treated by laparoscopic wedge resection or intragastric mucosal resection. Since technical and instrumental advances in endoscopic treatment were achieved by gastroenterologists, these cases can be managed by intraluminal endoscopic approaches. The attention of surgeons then shifted to more radical procedures such as laparoscopic gastrectomy with lymph node dissection, which is comparable to open surgery and can be indicated even in advanced cancer. Although this paradigm shift has already been realized in the field of colorectal surgery, we must pay attention to the particular biological nature of gastric cancer in terms of the potential of peritoneal dissemination. While early-phase recovery after surgery has been improved by laparoscopic surgery, preservation of late-phase QOL by function-preserving surgery is also essential in this regard; therefore, the sentinel node (SN) concept has been a much-discussed topic in gastric cancer surgery to approach this aspect. Recently, the validity of the SN concept has been demonstrated by a number of single institutional studies, and prospective multicenter trials are currently ongoing. Theoretically, various types of function-preserving surgery could be applied in cases of early gastric cancer with negative SNs as less invasive surgery to improve long-term QOL. Although we still have to solve several remaining issues in the treatment of gastric cancers, a confluence of these two major streams, laparoscopic surgery and sentinel node navigation surgery, would enable us to apply a novel individualized minimally invasive approach, both in terms of degree of incisional access and extent of function preservation.

Gastrectomy↗
PubMed2005

Partial resection of the second portion of the duodenum for gastrointestinal stromal tumor after effective transarterial embolization.

We report herein the case of 64-year-old man with gastrointestinal stromal tumor (GIST), who was treated by partial resection of the duodenum after preoperative transarterial embolization. He presented to our hospital with a history of tarry stools, dizziness, and severe anemia (hemoglobin, 7.5 g/dl). Gastroduodenal endoscopy revealed the presence of a submucosal tumor in the second portion of the duodenum. The presence of the tumor was subsequently confirmed by double-contrast gastrointestinal radiography and abdominal computed tomography. Super-selective angiography showed tumor staining fed from the anterior and posterior superior pancreaticoduodenal arteries, and the inferior pancreaticoduodenal artery. Two weeks after transarterial embolization through these vessels, the tumor size was found to have shrunk to 40% of its original size. Partial resection of the duodenum was performed and absence of tumor cells at the surgical margin was confirmed by intraoperative frozen-section examination. Histopathological examination revealed that the duodenal submucosal tumor consisted of spindle cells, and immunohistochemical analysis revealed positive tumor staining for c-kit protein, CD34 and alpha-smooth muscle actin (SMA), and negative staining for desmin and S-100; the positivity rate for MIB-1 staining was 2.2%. Based on these findings, the tumor was diagnosed as a GIST of low-grade malignancy, classified as the muscular type. It is considered that preoperative treatment of duodenal GISTs, such as transarterial embolization, may be useful for reducing the extent of resection, from pancreaticoduodenenctomy to a partial resection.

Duodenal Neoplasms↗
PubMed2005

Surgical site infection surveillance after open gastrectomy and risk factors for surgical site infection.

Surgical site infection (SSI) surveillance was examined in gastric cancer patients who had undergone an open gastrectomy between 1997 and 2003 at Keio University Hospital in Tokyo, Japan. National Nosocomial Infections Surveillance (NNIS) reports and several studies have discussed SSI risk factors, but only open gastrectomy was analyzed by regression analysis. The purpose of this study was to examine these issues by performing a regression analysis for the prediction of SSI. SSI was defined by the surgical patient component according to the NNIS system (1999) produced by the Centers for Disease Control and Prevention. Patients undergoing an open gastrectomy were followed up and monitored for SSIs. Risk factors for SSI, after all factors were considered, were studied using single and multivariate analysis. The study enrolled 984 patients who had undergoing an open gastrectomy. Using multivariate and logistic regression analysis, the duration of the operation was identified as a [corrected] risk factor for SSI at open gastrectomy. Although numerous potential risk factors in surgical patients were examined, the duration of the operation was the only significant risk factor for SSIs after open gastrectomy.

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↗
PubMed2005

Real-time RT-PCR (TaqMan) of tumor mRNA to predict sensitivity of specimens to 5-fluorouracil.

5-Fluorouracil (5-FU) is still a key drug in the treatment of various kinds of advanced cancer, including breast and gastrointestinal carcinomas. To predict the sensitivity of colorectal cancer to 5-FU, mRNA is extracted from surgically obtained cancer specimens and expression of thymidylate synthetase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), uridine phosphorylase (UP), es-nucleoside transporter (NT), and E2F1 are detected by real-time reverse transcription polymerase chain reaction (RT-PCR) (TaqMan). Previous results have shown that the catabolic rate-limiting enzymes DPD and NT, which are important membranous transporter of nucleosides, may regulate the sensitivity to 5-FU.

Antimetabolites, Antineoplastic↗
PubMed2005

Is chemoradiation effective or harmful for stage VI gastric cancer patients?

We aim to clarify beneficial effect of pre-operative radiation with chemotherapy in highly advanced gastric cancer patients, evaluating histological response, toxicity and patients' quality of life (QOL). We used pre-operative radiation with S-1 and low-dose cisplatin to treat 8 patients with highly advanced gastric cancer (clinical stage IV) in a pilot study. Clinical staging after therapy showed 5 PRs (partial response), 2 NCs (no change), and 1 PD (partial disease) following evaluation of the primary tumor and suspicious metastatic lesions in the lymph nodes, esophagus, liver, and peritoneum, for a response rate of 62.5% (5/8 cases). Of 8 patients, 6 underwent surgery, and 2 of these 6 patients had a histologically complete response (grade 3 effect) and 3 patients had a partial response (grade 2 effect), suggesting that a high histological response (5/6 cases; 83.3%) is expected by the chemoradiation. The survival analysis showed that 5 out of the 8 patients died within 10 months after initiating therapy, while 3 patients are alive without recurrence at 15, 18, and 30 months after therapy, suggesting a relatively good outcome for clinical stage IV gastric cancer. All cases showed grade 2-4 bone marrow suppression toxicity and/or grade 0-2 gastro-intestinal toxicity, while 5 out of 8 patients (62.5%) showed improvement in appetite loss at the end of the therapy, indicating that the patients' quality of life (QOL) was preserved. Chemoradiation may be a powerful regimen for obtaining histological response with tolerable toxicity and improved QOL in highly advanced gastric cancer patients.

Adult↗