Hisataka Fujiwara

Iwate Medical University, Morioka-shi, Iwate-ken, Japan

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Publications (21)33.1 Total impact

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    ABSTRACT: There has been a recent increase in the use of totally laparoscopic total gastrectomy (TLTG) for gastric cancer. However, there is no scientific evidence to determine which esophagojejunostomy (EJS) technique is the best. In addition, both short- and long-term oncological results of TLTG are inconsistent. We reviewed 25 articles about TLTG for gastric cancer in which at least 10 cases were included. We analyzed the short-term results, relationships between EJS techniques and complications, long-term oncological results, and comparative study results of TLTG. TLTG was performed in a total of 1170 patients. The mortality rate was 0.7%, and the short-term results were satisfactory. Regarding EJS techniques and complications, circular staplers (CSs) methods were significantly associated with leakage (4.7% vs. 1.1%, p < 0.001) and stenosis (8.3% vs. 1.8%, p < 0.001) of the EJS as compared with the linear stapler method. The long-term oncological prognosis was acceptable in patients with early gastric cancers and without metastases to lymph nodes. Although TLTG tended to increase surgical time compared with open total gastrectomy and laparoscopy-assisted total gastrectomy, it reduced intraoperative blood loss and was expected to shorten postoperative hospital stay. TLTG is found to be safer and more feasible than open total gastrectomy and laparoscopy-assisted total gastrectomy. At present, there is no evidence to encourage performing TLTG for patients with advanced gastric cancer from the viewpoint of long-term oncological prognosis. Although the current major EJS techniques are CS and linear stapler methods, in this review, CS methods are significantly associated with leakage and stenosis of the EJS.
    Asian Journal of Surgery. 11/2014;
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    ABSTRACT: Postoperative hyperglycemia is associated with infectious complications after various types of surgery. Our objective was to determine whether postoperative blood glucose levels up to 1 week after highly invasive esophageal cancer surgery are associated with the incidence of postoperative infections (POIs).
    Journal of Gastrointestinal Surgery 07/2014; · 2.36 Impact Factor
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    ABSTRACT: The aim of this study was to compare the outcomes of single-port laparoscopic gastric resection (SPLGR) with multiport laparoscopic gastric resection (MPLGR) for gastric gastrointestinal stromal tumors (GISTs). Between April 2009 and December 2012, 16 consecutive patients with gastric GISTs underwent SPLGR. The patients undergoing the SPLGR were case-matched for age, sex, body mass index and tumor location with those undergoing MPLGR. The demographic and surgical outcomes were analyzed and compared from the review of a prospectively collected database of 16 patients who underwent MPLGR. All 16 patients underwent complete SPLGR without any intraoperative complications. No significant differences were observed in the mean length of the operation (91.4 vs. 94.1 min), blood loss (6.3 vs. 10.1 ml) and length of postoperative hospital stay (4.7 vs. 5.4 days) between the SPLGR and MPLGR groups. The tumor size was similar (37.8 vs. 32.1 mm) and negative surgical margins were achieved in all patients. At a mean follow-up of 27 months, all 16 SPLGR patients were disease-free. Our initial comparison demonstrated that SPLGR, when performed by experienced surgeons, is a safe and feasible procedure for patients with gastric GISTs, resulting in good surgical and oncological outcomes.
    Surgery Today 08/2013; · 0.96 Impact Factor
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    ABSTRACT: We evaluated the outcome of esophageal stenting for esophagorespiratory fistula in patients with advanced esophageal cancer. Six patients with such fistula underwent esophageal stenting at our department from January 2000 to May 2012. Intraoral ingestion improved in all patients. Cough decreased immediately after stenting in 3 patients, and pneumonia detected by chest radiography improved within 1 week in 2 patients. Ventilation was weaned 2 days after stenting in 1 patient. The median survival duration after stenting was 31 days, and the cause of death was cancer in all patients. The following background factors were identified at the time of death: bleeding(n=3), mediastinitis(n=1), and pneumonia(n=1). Esophageal stenting, which should always be performed with the informed consent of the patient, improves respiratory symptoms, intraoral ingestion, and quality of life. Therefore, it is one of the best palliative therapies for patients with esophagorespiratory fistula associated with advanced esophageal cancer.
    Gan to kagaku ryoho. Cancer & chemotherapy 11/2012; 39(12):1849-51.
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    ABSTRACT: To confirm the clinical significance of NF-κB and JNK protein expression from experimentally identified candidates for predicting prognosis for patients with 5-FU treatment, we evaluated the protein expression of surgically removed specimens. A total of 79 specimens were obtained from 30 gastric and 49 colorectal cancer patients who underwent R0 resection followed by postoperative 5-FU based adjuvant chemotherapy. Immunohistochemical examinations of NF-κB and JNK on tissue microarrays (TMAs) revealed that significantly shorter time-to-relapse (TTR) in both NF-κB(+) and JNK(-) subgroups in both gastric (NF-κB(+), p = 0.0002, HR11.7. 95%CI3 3.2-43.4; JNK(-), p = 0.0302, HR4.4, 95%CI 1.2-16.6) and colon (NF-κB(+), p = 0.0038, HR36.9, 95%CI 3.2-426.0; JNK(-), p = 0.0098, HR3.2, 95%CI 1.3-7.7) cancers. These protein expression patterns also show strong discriminately power in gastric cancer patients for overall survival rate, suggesting a potential utility as prognostic or chemosensitivity markers. Baseline expression of these proteins using gastric cancer cell lines demonstrated the reciprocal patterns between NF-κB and JNK, while 5-FU exposure of these cell lines only induced NF-κB, suggesting that NF-κB plays a dominant role in the response to 5-FU. Subsequent siRNA experiments confirmed that gene knockdown of NF-κB increased 5-FU-specific sensitivity, whereas that of JNK did not affect the chemosensitivity. These results suggest that the expression of these proteins may aid in the decisions involved with adjuvant chemotherapy for gastrointestinal tract cancers.
    PLoS ONE 01/2012; 7(8):e43236. · 3.53 Impact Factor
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    ABSTRACT: We describe a 46-year-old man who presented with the chief complaint of lower back pain. The patient was diagnosed with advanced gastric cancer accompanied by multiple bone metastases, with compression fractures in the thoracolumbar vertebrae as well as distant lymph node metastases. He was administered eight courses of S-1/CDDP combination chemotherapy. Treatment results were as follows: primary lesion, non-CR/non-PD; lymph node metastases, CR; and bone metastases, non-CR/non-PD. As only the primary lesion showed a tendency toward progression after completion of eight courses, distal gastrectomy with D1 dissection was performed. Histopathological test results were ypT1b(SM1)and ypN1(2/22). The histological grade following treatment was grade 2 for both the primary lesion and the lymph nodes Following subsequent treatment with S-1 monotherapy and zoledronic acid, the disease did not progress, and at one year and four months since diagnosis and six months since surgery, CR and non-CR/non-PD have been maintained for the lymph node metastases and bone metastases, respectively.
    Gan to kagaku ryoho. Cancer & chemotherapy 01/2012; 39(1):115-8.
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    ABSTRACT: The patient was a 66-year-old male with adenocarcinoma of the esophagogastric junction and severe esophageal invasion, which was diagnosed as cType 3, cT4a (SE) cN3cM1 (LYM), cStage IV(histopathology: por 1). We tried concurrent chemoradiotherapy consisting of PTX 60 mg/m(2) and CDDP 25 mg/m(2), respectively (once a week), and a total of 45 Gy of radiotherapy treatment. Then, for effective continuation, chemotherapy using S-1 was performed as second-line therapy. A complete response was achieved and continued for more than 2 years after initial chemoradiotherapy; his complaints abated and his quality of life improved. Although gastro-intestinal symptoms and bone marrow suppression were observed as adverse effects, they were within a tolerable range and did not interfere with the concurrent chemoradiotherapy. This regimen appears to be feasible and effective for advanced gastric carcinoma refractory to other regimens.
    Gan to kagaku ryoho. Cancer & chemotherapy 10/2011; 38(10):1683-6.
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    ABSTRACT: We reviewed five patients with advanced gastroesophageal cancer who were successfully treated with chemoradiotherapy followed by a curative resection. Patients with histologically-documented adenocarcinoma of the gastroesophageal junction were eligible. Direct tumor extension into the stomach (cT3 or cT4), and involvement of lymph nodes were observed. The patients stopped receiving orally administered carcinostatic drugs due to digestive stenosis or tumor bleeding. They received 25 mg/m2 of cisplatin and 60 mg/m2 of paclitaxel once a week on days 1, 8, 15 and 22. Radiation was administered concurrently at a total dose of 45 Gy in 1.8 Gy fractions for over 25 treatments. Effectiveness of the therapy was evaluated 4 weeks after the chemoradiotherapy. All patients with clinical partial responses underwent gastrectomy (n=4) or esophagogastrectomy (n=1). Curative resection was performed in 5 patients (resection A/B 4/1), and no patient suffered from major postoperative complications. Four patients were downstaged according to the pathological findings. The histologically effective responses of all patients were Grade 2. The obvious chemotherapeutic efficacy of the present regimen suggested that it may be a good treatment option for advanced gastroesophageal cancers. Further studies including randomized controlled trials are needed to evaluate the significance of preoperative chemoradiotherapy.
    Gan to kagaku ryoho. Cancer & chemotherapy 11/2010; 37(11):2169-71.
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    ABSTRACT: Cancer cachexia, a catabolic state characterized by weight loss, occurs frequently in patients with terminal-stage neoplastic diseases. Gastrointestinal hormones and cytokines may be associated with anorexia and wasting in cancer cachexia. This study aimed to examine the mechanism of anorexia in cachectic patients through a prospective investigation of plasma cytokines, ghrelin, and leptin in 16 cachectic patients with cancer of the digestive organs and 10 healthy volunteers. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-1 receptor antagonist (IL-1Ra), and ghrelin levels were significantly higher in cachectic cancer patients than in the healthy volunteers, whereas leptin was significantly lower in the cachectic cancer patients. Plasma leptin levels and cytokine levels (TNF-alpha and IL-6) correlated significantly with body mass index (BMI), but plasma ghrelin levels did not correlate with BMI or with the grade of symptoms. Neither weight loss nor the grade of symptoms seemed to be directly associated with the increase in ghrelin levels. Hence, it is considered that the increase in ghrelin levels cannot simply be explained by an increase in ghrelin secretion, suggesting that other mechanisms, such as the decreased inactivation of ghrelin, may also play a role. Further studies are needed to clarify the mechanisms of the increase in ghrelin levels. Additionally, the changes in plasma cytokines (TNF-alpha and IL-6) and leptin in cachectic cancer patients suggest that these molecules may be useful markers for the evaluation of cancer cachexia.
    International Journal of Clinical Oncology 09/2009; 14(4):315-20. · 1.41 Impact Factor
  • Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association) 01/2007; 68(9):2229-2232.
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    ABSTRACT: To evaluate the ability of ultrasonically activated shears (USAS) to occlude lymphatic vessels, we investigated the bursting pressure of lymphatic vessels occluded with USAS and compared with pressures in an artery and a vein. The inguinal lymphatic vessels, testicular arteries, and testicular veins were removed from male pigs. The vessels were occluded by USAS at power level 2. The bursting pressures of the harvested vessels were measured ex vivo. The bursting pressure of the artery (average, 1154 mmHg; range, 1000-1341 mmHg) was significantly greater than that in the vein (average, 747 mmHg; range, 560-973 mmHg; p = 0.0024) or the lymphatic vessel (average, 610 mmHg; range, 491-996 mmHg; p = 0.0003). There was no significant difference of bursting pressure between the vein and lymphatic vessel (p = 0.2226). Although the bursting pressures of the vein and lymphatic vessel were significantly lower than that of the artery, they were much higher than that found in physiologic conditions. USAS is considered to be a powerful tool for lymph node dissection for malignant diseases in open surgery as well as laparoscopic surgery.
    World Journal of Surgery 02/2005; 29(1):106-9. · 2.23 Impact Factor
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    ABSTRACT: The patient was a 72-year-old female with gastric carcinoma. A liver metastatic recurrence was detected 27 months after operation. Although temporary partial responses were obtained by each effective chemotherapy, which was a combination chemotherapy with 5'-DFUR and TXT, TS-1 and TXL, the metastatic lesion proved refractory to all of them. Then we tried combination chemotherapy consisting of CDDP 30 mg/m2 and CPT-11 60 mg/m2, respectively (day 1 and 15, every 4 weeks). A partial response was achieved and continued for 8.5 months, and her complaints abated and quality of life improved. Although gastro-intestinal symptoms and bone marrow suppression were observed as side effects, they were within a tolerable range and did not interfere with the combination therapy. This regimen appears to be feasible and effective for recurrent gastric carcinoma refractory to other regimens.
    Gan to kagaku ryoho. Cancer & chemotherapy 12/2004; 31(12):2035-8.
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    ABSTRACT: To elucidate the mechanism of the enhanced antitumour activity of S-1 (1 M tegafur, 0.4 M 5-chloro-2, 4-dihydroxypyridine, and 1 M potassium oxonate) in terms of the phosphorylation and degradation pathways of 5-fluorouracil (5-FU) metabolism, we investigated tumoral thymidylate synthase (TS) content, dihydropyrimidine dehydrogenase (DPD) activity, the TS inhibition rate (TS-IR), and 5-FU incorporated into RNA (F-RNA) in four human gastric cancer xenografts (MKN-28, MKN-74, GCIY and GT3TKB) and compared the results obtained with S-1 with those obtained with 5-FU and UFT (1 M tegafur, 4 M uracil). 5-FU was administered intraperitoneally (i.p.) to mice at a dose of 50 mg/kg, three times, on days 0, 4 and 8. S-1 and UFT were administered orally at doses of 10 and 24 mg/kg, respectively, once a day, for 9 consecutive days. Antitumour activity was evaluated as the maximum inhibition of tumour growth in each animal. S-1 showed a better antitumour activity than 5-FU and UFT in tumours with a high DPD activity (GCIY and GT3TKB). There were inverse correlations between the antitumour activity and both TS content and DPD activity in the 5-FU and UFT groups. However, no such correlations were observed in the S-1 group. In GCIY and GT3TKB xenografts, TS-IR was significantly higher in the S-1 group than in the 5-FU or UFT groups. In GT3TKB xenografts, the F-RNA level was significantly higher in the S-1 group than in the 5-FU or UFT groups. The superior cytotoxicity of S-1 appears to be attributable to both an increased inhibition of DNA synthesis and an enhanced blockade of RNA function against tumours with a high DPD activity.
    European Journal of Cancer 12/2003; 39(16):2387-94. · 5.06 Impact Factor
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    ABSTRACT: To improve the therapeutic efficacy and minimize the toxicity of 5-fluorouracil (5-FU), intermittent therapy consisting of alternate 24-h intravenous infusion and based on differences in generation time (T(G)) between normal cells and tumor cells was investigated. Two human gastric cancer cell lines MKN-7 and MKN-74 with T(G) of 35 h and 17 h, respectively, were used in an in vitro cytotoxic assay. The drug exposure schedule consisted of a continuous 144-h exposure and alternate 24-h exposures. In a clinical trial, a total of 23 patients with advanced or recurrent gastric cancer were treated with intermittent therapy consisting of 24-h intravenous infusion with 5-FU 700 mg/m(2) per day on days 1, 3 and 5 in combination with low-dose cisplatin (CDDP) at 3.3 mg/m(2) per day on days 1 to 5. One cycle of the combined chemotherapy lasted for four consecutive weeks, followed by withdrawal over 1-2 weeks. Plasma 5-FU concentrations were measured by high-performance liquid chromatography in 15 patients and dihydropyrimidine dehydrogenase (DPD) activity in peripheral blood mononuclear cells (PBMC) was measured in 13 patients. The in vitro study revealed no statistically significant difference in cytotoxicity of 5-FU between the two drug exposure schedules in MKN-7 cells. In MKN-74 cells, however, a statistically significant decrease in cytotoxicity was found with the alternate 24-h exposure. In a clinical trial, plasma 5-FU concentrations showed a trapezoidal pattern. There was a significant correlation between DPD activity in PBMC and total body clearance of 5-FU. There were eight partial responders (8/22, 36%). Toxicities were very mild in severity, with no grade 3 or 4 toxicity. In particular, diarrhea and stomatitis were infrequent (one patient), and none of the patients developed thrombocytopenia. Toxicities which may be observed in rapidly growing cells such as bone marrow cells and gastrointestinal epithelial cells following continuous intravenous infusion of 5-FU seemed to be reduced by intermittent therapy of 5-FU consisting of alternate 24-h intravenous infusions.
    Cancer Chemotherapy and Pharmacology 04/2003; 51(3):240-6. · 2.80 Impact Factor
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    ABSTRACT: This study was designed to investigate the role of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and thymidine phosphorylase (TP) in tumor progression and sensitivity to 5-fluorouracil (5-FU). A total of 275 tumor samples from 275 patients with gastric cancer were utilized in this study. TS activity was determined in 130 samples by 5-fluorodeoxyuridine monophosphate binding assay. DPD activity was measured in 140 samples by radioenzymatic assay, and TP protein level was determined in 157 samples by an enzyme-linked immunosorbent assay (ELISA) system. These parameters were compared with several clinicopathologic factors and sensitivity to 5-FU determined by in-vitro ATP assay. The antitumor activities of 5-FU, uracil plus tegafur (UFT), and 1M tegafur--0.4 M 5-chloro-2,4-dihydroxypyridine--1 M potassium oxonate (S-1 [TS-1]) were also compared, using three human gastric cancer xenografts in nude mice. There was no correlation between either TS or TP and sensitivity to 5-FU. However, a weak inverse correlation was found between DPD activity and sensitivity to 5-FU. High DPD activity in tumor resulted in poor prognosis, especially in patients who received 5-FU-based adjuvant chemotherapy. Although TP was significantly correlated with depth of tumor invasion and with lymphatic and venous invasions, TP alone had no impact on survival. On the other hand, TS, as well as peritoneal, hepatic, and lymph node metastases, was selected as an independent prognostic factor in gastric cancer. In the animal model, there was no significant difference in antitumor activities among the drugs in a tumor with low DPD activity. However, S-1 showed superior antitumor activity to 5-FU or UFT in tumors with high DPD activity. DPD is considered to be a most important predictive factor of 5-FU sensitivity. The use of DPD inhibitory fluoropyrimidines is strongly recommended for tumors with high DPD activity.
    Gastric Cancer 02/2003; 6 Suppl 1:71-81. · 3.99 Impact Factor
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    ABSTRACT: This study was designed to investigate the role of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) on tumour progression and sensitivity to 5'-deoxy-5-fluorouridine (5'-DFUR). Tumour tissue was obtained from surgically resected samples from 93 patients with primary gastric cancer. Tumour TP and DPD expression levels were determined by the enzyme-linked immunosorbent assay (ELISA) system and compared with several clinicopathological factors and in vitro sensitivity to 5'-DFUR. DPD showed no correlation with any clinicopathological factors. However, the TP level was significantly correlated with the depth of tumour, lymphatic invasion and venous invasion. In comparison with 5'-DFUR sensitivity, there was a weak inverse correlation between the DPD level and the sensitivity to 5'-DFUR (r(s)=-0.361). Furthermore, the TP/DPD ratio showed a significant correlation with 5'-DFUR sensitivity (r(s)=0.634). In a subgroup of patients with postoperative 5'-DFUR administration, the survival rate was significantly better in patients with a high TP/DPD ratio (n=8) than in those with low TP/DPD ratio (n=14) (P=0.0140). These results suggest that sensitivity to 5'-DFUR is predictable by measurement of both TP and DPD levels.
    European Journal of Cancer 01/2003; 38(18):2375-81. · 5.06 Impact Factor
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    ABSTRACT: We used real-time reverse-transcription polymerase chain reaction (RT-PCR) to assay expression of the mRNA of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) in gastric cancer tissue with the objective of establishing a system to measure TS and DPD in ultra-low-volume samples. Nude mouse xenografts of 5 human gastric cancer cell lines and 85 clinical samples were used as the specimens in this study. Sensitivity to 5-fluorouracil (5-FU) was determined on the basis of the relative tumor proliferation rate in mice and the results of ATP assay using serum-free cultures of the clinical samples. mRNA expression was measured in tumor tissue by real-time RT-PCR using the ABI PRISM 7700 system. The values for expression of the mRNA for TS and DPD were corrected according to the level of glyceraldehyde-3-phosphate dehydrogenase mRNA expression. The xenografts yielded correlations between TS and DPD mRNA expression and the activity of the enzymes (TS: rs=0.700, DPD: rs=0.900), and an inverse correlation was noted between the mRNA levels and sensitivity to 5-FU (TS: rs=-0.900, DPD: rs=-0.800). The clinical samples showed an inverse correlation between 5-FU sensitivity and mRNA expression (TS: rs=-0.518, DPD: rs=-0.564). Sensitivity to 5-FU was noted only in cases in which TS mRNA expression and DPD mRNA expression were both low. Real-time RT-PCR can provide a highly sensitive assessment of TS and DPD mRNA expression in gastric cancer, and it was useful for predicting 5-FU sensitivity.
    Japanese journal of cancer research: Gann 01/2003; 93(12):1342-50.
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    ABSTRACT: In order to evaluate the utility of combination chemotherapy with intra-peritoneal infusion of CDDP and continuous intravenous infusion of 5-FU, we performed this therapy in 23 primary gastric cancer patients with peritoneal metastasis. CDDP was administered intraperitoneally at a dose of 70 mg/m2 over 2 hours on day 1, and 5-FU was continuously administered intravenously at a dose of 700 mg/m2 for 5 consecutive days from day 1, respectively. This treatment was given twice. Median survival time with this treatment was 343 days, and the depth of invasion was selected as an independent prognostic factor according to multivariate analysis. Five patients (21.7%) have survived more than 3 years. Major toxicities were less than Grade 2 except for two patients with each anemia (Grade 3) and venous thrombosis (Grade 3), respectively. This regimen appears to be feasible and effective for gastric cancer patients with peritoneal metastases. Long term survival may be obtained in patients without adjacent organ invasion.
    Gan to kagaku ryoho. Cancer & chemotherapy 12/2002; 29(12):2342-5.
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    ABSTRACT: The role of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) enzyme activities in tumor progression and sensitivity to 5-fluorouracil (5-FU) were evaluated. TS and DPD activities were measured in 81 clinical samples of gastric cancer. TS and DPD activities were determined by 5-fluorodeoxyuridine monophosphate binding assay and by radioenzymatic assay, respectively. Sensitivity to 5-FU was determined by in vitro ATP assay. There was no correlation between TS activity and sensitivity to 5-FU. However, a weak correlation was found between DPD activity and sensitivity to 5-FU. In a subgroup of patients who did not receive adjuvant chemotherapy, overall survival was poorer in patients with high TS activity (p=0.0265). Conversely, in a subgroup of patients who received 5-FU-based adjuvant chemotherapy, overall survival was poorer in patients with high DPD activity (p=0.0465). These results suggest that TS has an important role in tumor progression and DPD may be the dominant predictor of 5-FU sensitivity in gastric cancer.
    Anticancer research 01/2002; 22(2A):761-8. · 1.71 Impact Factor
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    ABSTRACT: A combination chemotherapy with intra-peritoneal infusion of CDDP and continuous intravenous infusion of 5-FU was used with a total of 16 gastric cancer patients with peritoneal metastasis (P 2 or P 3). Infuse A-port was inserted at the time of operation, CDDP 70 mg/m2 was administered intra-peritoneally at day 1, and 5-FU 700 mg/m2 was continuously administered intravenously at day 1-5. This treatment was repeated twice. Toxicity was evaluated according to the criteria from JCOG. Major toxicities of this regimen were anemia, leukocytopenia and nausea/vomiting. Except for one patient with Grade 3 venous thrombosis, all toxicities were less than Grade 2 and well tolerable. Median survival time was 343 days, but, one patient has survived more than 6 years. According to the multivariate analyses, depth of invasion was selected as an independent prognostic factor for this treatment. This therapy is considered to be a safe and effective treatment modality for gastric cancer patients with peritoneal metastasis.
    Gan to kagaku ryoho. Cancer & chemotherapy 11/1999; 26(12):1806-8.