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The KEYNOTE-659 study evaluated the efficacy and safety of first-line pembrolizumab plus S-1 and oxaliplatin (SOX) (cohort 1) or S-1 and cisplatin (SP) (cohort 2) for advanced gastric/gastroesophageal junction (G/GEJ) cancer in Japan. Herein, we update the results of cohort 1 and describe the results of cohort 2. This open-label phase IIb study enrolled patients with advanced programmed death-ligand 1 (PD-L1)-positive (combined positive score ≥ 1) human epidermal growth factor receptor 2 (HER2)-negative G/GEJ adenocarcinoma. The primary end-point was the objective response rate (ORR). Other end-points were duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. One hundred patients were enrolled. In cohorts 1 and 2, median follow-up time was 16.9 and 17.1 months; ORR (central review), 72.2% and 80.4%; DOR, 10.6 and 9.5 months; DCR (central review), 96.3% and 97.8%; median PFS (central review), 9.4 and 8.3 months; and median OS, 16.9 and 17.1 months, respectively. Treatment-related adverse events (TRAEs) occurred in all patients, including peripheral sensory neuropathy (94.4%, cohort 1), decreased neutrophil count (82.6%, cohort 2), nausea (59.3% and 60.9% in cohorts 1 and 2), and decreased appetite (61.1% and 60.9% in cohorts 1 and 2). Grade 3 or higher TRAEs were reported by 59.3% (cohort 1) and 78.3% (cohort 2), including decreased platelet count (14.8%, cohort 1) and decreased neutrophil count (52.2%, cohort 2). Pembrolizumab in combination with SOX or SP showed favorable efficacy and safety in patients with PD-L1-positive, HER2-negative G/GEJ adenocarcinoma., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: A multi-institutional phase II study was conducted to evaluate the efficacy and safety of preoperative docetaxel, cisplatin and S-1 therapy in marginally resectable advanced gastric cancer., Methods: Patients with macroscopic type 4, large macroscopic type 3 and bulky lymph node metastasis received two cycles of preoperative docetaxel, cisplatin and S-1 therapy (docetaxel 40 mg/m2 and cisplatin 60 mg/m2 on day 1, and S-1 80 mg/m2 for 14 days, every 4 weeks). The primary endpoint was the pathological response rate, with an expected value of 65%., Results: Thirty-one patients were enrolled in this study. The pathological response rate was 54.8%, and it was higher than the threshold value but lower than the expected rate. The R0 resection rate was 93.5%. The frequencies of grade 3-4 toxicities during docetaxel, cisplatin and S-1 therapy were 41.9% for neutropenia, 6.5% for febrile neutropenia and 32.3% for nausea/vomiting. Grade 2 and 3 surgical morbidities occurred in 23.3 and 6.7% of the patients, respectively., Conclusions: Preoperative docetaxel, cisplatin and S-1 therapy was feasible in terms of chemotherapy-related toxicities and surgical morbidity, but the effect did not achieve the expected value. The association between the pathological response rate and survival will be evaluated in the final analysis of this clinical trial., (© The Author(s) 2020. Published by Oxford University Press.)

Aim: The KEYNOTE-659 study evaluated the efficacy and safety of pembrolizumab in combination with chemotherapy as the first-line treatment in Japanese patients with advanced gastric/gastroesophageal junction (G/GEJ) cancer. In this paper, we report results from cohort 1 (S-1 plus oxaliplatin [SOX] with pembrolizumab)., Methods: This was a non-randomised, multicentre, open-label phase IIb study in patients with advanced programmed death-ligand 1 (PD-L1)-positive, human epidermal growth factor receptor 2-negative G/GEJ tumours. The primary endpoint was the objective response rate (ORR) assessed by blinded independent central review (BICR). Secondary endpoints were duration of response (DOR), disease control rate (DCR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and safety. Exploratory analyses were performed based on the PD-L1 combined positive score (CPS) status., Results: Fifty-four patients were evaluated. The median follow-up was 10.1 months. ORR and DCR by BICR were 72.2% (95% confidence interval [CI] 58.4-83.5) and 96.3% (95% CI 87.3-99.5), respectively. Median DOR, TTR, PFS and OS were as follows: not reached, 1.5 months, 9.4 months and not reached. The ORR was 73.9% in patients with CPS ≥1 to <10 and 71.0% in those with CPS ≥10. Grade ≥3 treatment-related adverse events (TRAEs) were reported by 57.4% of patients. The most common grade ≥3 TRAEs were decreased platelet count (14.8%), decreased neutrophil count (13.0%), colitis (5.6%) and adrenal insufficiency (5.6%)., Conclusions: SOX with pembrolizumab showed encouraging efficacy and a manageable safety profile for the first-line treatment of advanced G/GEJ cancer., Trial Registration: NCT03382600/JapicCTI-183829., Competing Interests: Conflict of interest statement Y. Negoro, M. Tsuda, S Shiratori, S.R. Han and T. Oshima, declare no conflicts of interest. A. Kawazoe reports grants and personal fees from Taiho Pharmaceutical and Ono Pharmaceutical and grants from Sumitomo Dainippon Pharma and MSD, outside the submitted work. N. Machida reports personal fees from Taiho Pharmaceutical and MSD, during the conduct of the study. K. Yamaguchi reports grants and personal fees from Taiho, grants from MSD, during the conduct of the study; grants and personal fees from Chugai Pharm, personal fees from Takeda, personal fees from Merck Serono, personal fees from Bayer, grants and personal fees from Daiichi-Sankyo, grants and personal fees from Ono Pharm, grants and personal fees from Lilly Japan, grants from Gilliad, grants from Dainippon Sumitomo, grants from Boehringer Ingelheim, personal fees from Bristol and grants from Sanofi, outside the submitted work. H. Yasui reports personal fees from Taiho Pharmaceutical and Yakult Honsha and grants from MSD, during the conduct of the study; personal fees from Chugai Pharmaceutical, Bristol-Myers Squibb Japan and Eli Lilly Japan; grants and personal fees from Daiichi Sankyo and grants from Ono Pharmaceutical, outside the submitted work. M. Azuma reports grants and personal fees from Taiho Pharmaceutical during the conduct of the study and grants and personal fees from Ono Pharmaceutical, outside the submitted work. K. Amagai reports grants from MSD, during the conduct of the study; grants from MSD, Taiho Pharmaceutical, Bayer, Hisamitsu and Daiichi Sankyo, outside the submitted work. H. Hara reports grants from Japan Agency for Medical Research and Development (AMED) during the conduct of the study; grants from AstraZeneca, Sumitomo Dainippon Pharma, Merck Serono, Eisai, LSK BioPharma, Incyte, Pfizer, Boehringer-Ingelheim and BeiGene; grants and personal fees from Daiichi Sankyo, MSD, Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical and BMS and personal fees from Eli Lilly, Yakult Honsha, Sanofi and Takeda Pharmaceutical, outside the submitted work. H. Baba reports grants, personal fees and non-financial support from Taiho Pharmaceutical, during the conduct of the study; grants, personal fees and non-financial support from Ono Pharmaceutical and Eli Lilly Japan; grants and personal fees from Takeda Pharmaceutical and Chugai Pharmaceutical; grants and non-financial support from Merck Serono, Yakult Honsha and Johnson & Johnson and grants from Shionogi & Co, Covidien Japan, Takeda Pharmaceutical, Shin Nippon Biomedical Laboratories, Novartis and Toyama Chemical, outside the submitted work. H. Hosaka reports grants from Taiho Pharmaceutical, Ono Pharmaceutical and Bristol-Myers Squibb, outside the submitted work. H. Kawakami reports personal fees from Bristol-Myers Squibb, Eli Lilly, Taiho Pharmaceutical, Ono Pharmaceutical, Takeda Pharmaceutical, MSD, AstraZeneca, Bayer and Yakult Honsha; grants and personal fees from Chugai Pharmaceutical, Daiichi Sankyo and grants from Eisai, outside the submitted work. Y. Omuro reports grants from MSD, during the conduct of the study and grants from Ono Pharmaceutical, Five Prime, Daiichi Sankyo, Astellas and BeiGene, outside the submitted work. T. Esaki reports grants from Astellas, MSD, Sumitomo Dainippon Pharma, Nihon Kayaku, Novartis and Pfizer; grants and personal fees from Daiichi-Sankyo, Ono Pharmaceutical, Merck Serono, Taiho Pharmaceutical, Eli Lilly, Bayer, Bristol-Myers Squibb; personal fees from Takeda Pharmaceutical, Kyowa Kirin, Chugai Pharmaceutical, Eisai and Sanofi, outside the submitted work. K. Yoshida reports grants and personal fees from Taiho Pharmaceutical and MSD, during the conduct of the study; grants and personal fees from Asahi Kasei Pharma, Chugai Pharmaceutical, Covidien Japan, Daiichi Sankyo, Eisai, Eli Lilly Japan, Johnson & Johnson, Merck Serono, Nippon Kayaku, Novartis, Ono Pharmaceutical, Otsuka Pharmaceutical, Sanofi, Tsumura and Yakult Honsha; grants from Abbott, AbbVie, Astellas, Biogen Japan, Celgene, GlaxoSmithKline, KCI, Kyowa Kirin, Meiji Seika Pharma and Toray Medical and personal fees from AstraZeneca, Bristol-Myers Squibb, Denka, EA Pharma, Olympus, Pfizer, Sanwa Kagaku Kenkyusho, SBI Pharma, Takeda Pharmaceutical, Teijin Pharmaceutical and TERUMO, outside the submitted work. T. Nishina reports grants and personal fees from Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb and Eli Lilly and grants from Daiichi Sankyo, MSD and Sumitomo Dainippon Pharma, outside the submitted work. Y. Komatsu reports grants and personal fees from Taiho Pharmaceutical, during the conduct of the study; grants and personal fees from Eli Lilly Japan K.K., Taiho Pharmaceutical, Chugai Pharmaceutical, Takeda Pharmaceutical, Bayer Yakuhin, Ltd., Bristol-Myers Squibb, Sanofi S.A., Merck Biopharma, Ono Pharmaceutical, MSD K.K., Yakult Honsha, Otsuka Pharmaceutical; grants from National Cancer Center Hospital, NanoCarrier, Baxter International Inc., Clinical Co., Ltd., Quintiles and IMS Health, Sysmex Corporation, Mediscience Planning Inc., Sumitomo Dainippon Pharma, Kyowa Kirin, Asahi Kasei Pharma Corporation and Nippon Zoki Pharmaceutical, outside the submitted work. K. Shitara reports grants and personal fees from Astellas Pharma, Eli Lilly, Ono Pharmaceutical and MSD; personal fees from Bristol-Myers Squibb, Takeda Pharmaceutical, Pfizer, Novartis, AbbVie and Yakult Honsha; grants from Sumitomo Dainippon Pharma, Daiichi Sankyo, Taiho Pharmaceutical, Chugai Pharmaceutical and MediScience, outside the submitted work., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The aim of the present study was to evaluate the clinical impact of the perioperative use of antiplatelet/anticoagulation therapy for postoperative bleeding after esophagectomy for esophageal cancer., Patients and Methods: Patients were selected from the medical records of consecutive patients who were diagnosed with primary esophageal adenocarcinoma or squamous cell carcinoma and who underwent complete resection at Yokohama City University from January 2005 to September 2018. The patients were divided into the antiplatelet/anticoagulation treatment group and the non-treatment group. We compared the safety and feasibility of esophagectomy between two groups., Results: One hundred and twenty-two patients underwent esophagectomy for esophageal cancer and were analyzed in the present study. Among them, 18 (14.8%) received anti-thrombotic therapy (anticoagulation group). The incidence of postoperative bleeding in patients overall was 8.2% (10/122). The incidence of postoperative bleeding in the anticoagulation group was 22.2% (4/18), while that in the non-anticoagulation group was 5.8% (6/104). Preoperative anticoagulation therapy was identified as a significant independent risk factor for postoperative bleeding (hazard ratio=4.673, 95% confidence interval=1.170-18.519; p=0.029)., Conclusion: The perioperative use of anti-thrombotic therapy was a significant risk factor for postoperative bleeding after esophagectomy for esophageal cancer. Thus, when patients receive perioperative antiplatelet/anticoagulation treatment, careful attention is required after esophagectomy due to their increased risk of postoperative bleeding., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: The enzymes gamma-glutamyl hydrolase (GGH) and folylpolyglutamate synthetase (FPGS) regulate intracellular folate concentrations needed for cell proliferation, DNA synthesis, and repair. High GGH expression affects 5-FU thymidylate synthase (TS) inhibition and is a risk factor for various malignancies. Here, the clinical significance of GGH and FPGS expression was investigated in Stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1., Methods: Surgical specimens of cancer tissue and adjacent normal mucosa, obtained from 253 patients with previously untreated gastric cancer, were examined. GGH and FPGS mRNA expression was measured by qPCR to evaluate their clinicopathological significance in gastric cancer patients after curative resection., Results: While FPGS expression showed no significant differences between the cancerous and normal samples, GGH expression was higher in cancer tissue than in adjacent normal mucosa. High GGH expression was correlated with age, histological type, and vascular invasion. Overall survival (OS) of patients with high GGH mRNA expression was significantly poorer than of patients with low GGH expression. Multivariate analysis showed that high GGH expression was an independent prognostic factor of OS (HR: 2.58, 95% CI 1.29-5.16). Patients who received S-1 adjuvant treatment showed a significantly poor OS between high GGH/low FPGS and low GGH/high FPGS. Patients without adjuvant treatment showed no significant difference., Conclusion: GGH expression was significantly higher in gastric cancer tissue than in adjacent normal mucosa. High GGH and low FPGS expression is a useful independent predictor of poor outcomes in stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1.

A 66-year-old woman diagnosed with advanced Stage Ⅳ gastric cancer(T4aN3M1[LYM])received RAM plus wPTX as third-line chemotherapy(ramucirumab 8mg/kg on the 1st and 15th day, paclitaxel 80mg/m2 on the 1st, 8th, and 15th day).After receiving 3 courses of this treatment, para-aortic lymphadenopathy had diminished but anemia had progressed because of tumor hemorrhage.Six weeks after the last administration of RAM, an open distal gastrectomy with D1 plus lymph node dissection and Billroth Ⅰ reconstruction was performed.The patient was discharged on the 9th day after surgery without complications such as postoperative bleeding and delayed wound healing.RAM plus wPTX therapy was restarted 6 weeks after the operation.Postoperative late complication there is no adverse event including adenocarcinoma and continues the same therapy at present.The perioperative treatment under the use of angiogenesis inhibitor has risk of postoperative bleeding and wound healing delay and includes surgery timing of treatment may be difficult.In our case, surgery was performed 6 weeks after the final administration of RAM.

This is a case of a 70-year-old man. Two courses of docetaxel/cisplatin/S-1 combination therapy were administered after clinical trial registration with diagnosis of Stage Ⅳ gastric cancer(ypT3N3aM1). In June 2014, gastrectomy and splenectomy were performed. Postoperative S-1 adjuvant chemotherapy was administered; however, in September 2014, aorticl ymph node metastasis was diagnosed as recurrent. After recurrence, irinotecan/cisplatin therapy was administered. In February 2015, recurrent lymph node metastasis increased, and chemotherapy was changed to paclitaxel. In May 2015, numbness (Grade 2)of the fingers was observed, and treatment was changed to oxaliplatin/S-1. In February 2016, storage of ascites became remarkable; therefore, chemotherapy was discontinued as per policy. After that, we continued outpatient visit and observed increased recurrent lymph node metastasis on image evaluation; however, as the patient's general condition was good, chemotherapy was restarted. Ramucirumab/paclitaxel therapy started in February 2017. During the course of treatment, neutropenia(Grade 2)was observed as an adverse event, but therapy continuation was possible without loss of ramucirumab only with loss of paclitaxel. Thereafter, the recurrence of lymph node metastasis was reduced, and the ascites accumulation decreased. Until now, 1 year after the start of ramucirumab/paclitaxel therapy, the patient still visits the outpa- tient clinic.

Although chemotherapy is the standard treatment for unresectable advanced gastric cancer, its prognosis is poor and the median survival time is only around 10 months. With some literature consideration, we report that ovarian metastasis triggered the diagnosis of unresectable advanced gastric cancer with long-term survival through multidisciplinary treatment. This is the case of a 69-year-old woman, who was diagnosed with ovarian tumor and underwent right extracorporectomy and omentum resection in 2011. Pathological diagnosis suspected adenocarcinoma. In February 2012, EGD found a type 4 tumor in the upper portion of the pyloric area of the stomach. She was diagnosed with gastric cancer with Stage IV(T4aN0M1 [ovary])ovarian metastasis. Because the primary tumor was HER2 positive, XP plus HER therapy(capecitabine 1,000mg/m2 twice a day for 14 days, CDDP 80mg/m2 every 3 weeks on the first day, and trastuzumab 8 mg/kg every 3 weeks on the first day)was administered since March 2012. No metastasis was found in the imaging examination after 8 courses of chemotherapy, and we also confirmed the reduction of the primary tumor in the EGD. Based on the images, primary resection was already possible. In December 2012, after a diagnostic laparoscopy, total gastrectomy with D2 lymph node dissection was performed. Postoperative pathology was diagnosed as Stage IV(pT4aN0M1). To control postoperative micrometastasis, capecitabine therapy(1,000mg/m2 twice a day for 14 days)was administered for 12 months starting from February 2013. Then, recurrence and metastasis were not observed during follow-up. However, in January 2017, a circumstellar stenotic tumor was found in the rectum and was diagnosed as recurrence of peritoneal dissemination through images. In February 2017, artificial ostomy(in the sigmoid colon, double-mouth type)was made. Then, the patient underwent an outpatient chemotherapy, with hospital visits, and she survives.

We report a case of Stage IV gastric cancer showing pathological complete response(pCR)after neo-adjuvant chemotherapy( NAC)using S-1 and oxaliplatin(SOX).A woman 73-year-old was diagnosed as harming type 3 Stage IV gastric cancer with para-aortic lymph node(PAN)metastasis.She underwent 4 courses of NAC with SOX regimen.After the treatment, both the primary tumor and the metastatic PAN decreased in size remarkably.She underwent distal gastrectomy with D2 plus PAN dissection with curative intent.Pathological diagnosis revealed complete disappearance of cancer cells in both the primary lesion of the stomach and all dissected lymph nodes, confirming pCR.She is alive without recurrence 4 months after surgery.

The standard therapy for Stage IV gastric cancer is chemotherapy. It is not certain, but conversion surgery is expected to be effective. We report the cases of 3 patients who achieved long-term survival after conversion surgery. Case 1 was of a 59- year-old woman. The tumor was classified as L-Less Post, Type 2, tub1, cT3N2M1(#16a2lat), Stage IV. Then, we initiated S-1 plus cisplatin and the LN achieved PRafter 4 courses. We performed distal gastrectomy with D2 lymph node dissection in February 2011. It was classified as ypT2N2 and the primary lesion was histologically classified as Grade 1a. Case 2 was of a 74- year-old man. The tumor was classified as UM-Less Ant, Type 3, por1, cT3N2H0P1CY1, Stage IV. Then, we initiated docetaxel plus cisplatin plus S-1 and the primary tumor achieved PRafter 6 courses. There were no new tumors and we conducted a laparoscopic examination. After the decision of P0CY0, we performed total gastrectomy with D2 lymph node dissection in April 2012. It was classified as ypT3N1 and the primary lesion was histologically classified as Grade 2. Case 3 was of a 64-yearold woman. The tumor was classified as UM-Less, Type 3, por1, cT3N2H1M0(liver), Stage IV. Then, we initiated capecitabin plus cisplatin and liver metastasis achieved PRafter 6 courses. We performed total gastrectomy with D2 lymph node dissection in July 2012. It was classified as ypT3N1 and the primary lesion was histologically classified as Grade 1b. All postoperative chemotherapy courses were of only S-1. In case 1, the para aortic LN exhibited recurrence 6 months postoperatively. We initiated weekly paclitaxel as second-line therapy. It achieved CRafter 6 courses, and the same trend was maintained. In cases 2 and 3, no therapy was administered after 8 S-1 courses, but no recurrences occurred. All patients survived after 62-77 months postoperatively. A new clinical trial is needed to prove the improvement in prognosis for Stage IV gastric cancer after conversion surgery.

A 63-year-old man underwent low anterior resection for rectal cancer.A synchronous liver metastasis located in segment 8 was 12 cm in diameter and unresectable due to its proximity to the inferior vena cava(IVC).The postoperative pathological findings revealed a T3(SS), N0, M1(liver)Stage IV tumor, and wild type K-RAS was expressed.We chose FOLFIRI plus cetuximab(Cmab)for first-line chemotherapy.After 6 courses, we changed the molecular target drug from Cmab to bevacizumab( Bmab)because the liver metastasis remained unresectable.The patient had long-term stable disease(SD)for approximately 30 months with the FOLFIRI-based regimen.We then changed the regimen to mFOLFOX6 plus Bmab for second-line, Cmab for third-line, and trifluridine/tipiracil hydrochloride for fourth-line chemotherapy to treat progressive disease(PD).After treatment with these chemotherapies, the patient wished to continue treatment.We restarted FOLFIRI plus Bmab for fifth-line chemotherapy as his general condition was still good.Consequently, his tumor markers levels decreased with stabilization of the disease on CT scans, and he continued therapy for 6 months while maintaining a good quality of life.This case suggested that rechallenge with anti-cancer agents could be effective and improve the prognosis of colorectal cancer patients after using all key drugs.

Purpose: Curative resection and adjuvant chemotherapy is the standard treatment for Stage II/III gastric cancer, and S-1 is widely used for adjuvant chemotherapy. The type 1 insulin-like growth factor receptor (IGF1R) is involved in cell proliferation and prevention of apoptosis in many tumors. We evaluated the relative expression of the IGF1R gene to determine whether such expression correlates with outcomes in patients with Stage II/III gastric cancer., Methods: We measured the expression levels of the IGF1R gene in specimens of cancer and adjacent normal mucosa obtained from 134 patients with Stage II/III gastric cancer who received curative resection and adjuvant chemotherapy with S-1. We then evaluated whether the IGF1R gene expression levels correlate with clinicopathological characteristics and outcomes., Results: IGF1R mRNA expression levels tended to be higher in cancer tissue than in the normal adjacent mucosa (P = 0.078). Multivariate analysis showed that high IGF1R gene expression was a significant independent predictor of poor survival in Stage II/III gastric cancer after curative resection and adjuvant chemotherapy with S-1 (HR 3.681, P = 0.007). The overall survival rate was significantly lower in patients with high IGF1R gene expression than in those with low expression (P = 0.012)., Conclusions: IGF1R overexpression is considered a useful independent predictor of outcomes in Stage II/III gastric cancer after curative resection and adjuvant chemotherapy with S-1.

A 35-year-old man was diagnosed to have gastric cancer by endoscopic and histological examinations. Staging laparoscopy detected peritoneal metastasis. Systemic chemotherapy was started, but the patient complained of severe headache. Subsequently, a lumbar puncture demonstrated adenocarcinoma cells in the spinal fluid, suggesting the occurrence of meningeal carcinomatosis (MC) from gastric cancer. MC occurs only rarely in patients with gastric cancer, but the prognosis is invariably poor. However, this patient nevertheless survived for 12 months after receiving intrathecal MTX/Ara-C together with systemic chemotherapy. Therefore, the early detection of meningeal irritation sign and intrathecal chemotherapy might greatly improve the prognosis of gastric cancer patients with MC.

A 67-year-old woman was referred to our hospital for type 1 gastric cancer. We diagnosed the patient with advanced gastric cancer (tub2>por, HER2-positive), and the clinical findings were T4aN1M1 (lung), Stage Ⅳ. The patient had cancer cachexia. As first-line chemotherapy, a regimen consisting of capecitabine (X) (1,600 mg/m2/day, days 1-14), cisplatin (P) (60 mg/m2/day, day 1), and trastuzumab (H) (8 mg/kg/day>6 mg/kg/day, day 1) was administered every 3 weeks and repeated 6 times. After receiving 6 courses, the patient's general condition and cancer cachexia symptoms improved. The size of the primary lesion significantly decreased, and lung metastasis was not visible on a PET scan. Simultaneously, a new 0-Ⅱc tumor was detected in the cardia, and a biopsy revealed a malignant lymphoma. Total gastrectomy and D2 lymph node dissection without splenectomy were performed. The final diagnosis was T4aN0M0. After treatment, the tumor was histologically evaluated as Grade 1b, and the remnant cancer cells were found to be HER2-negative (loss of HER2). The patient has been alive for 5 months and is receiving adjuvant chemotherapy comprising capecitabine and trastuzumab. Following chemotherapy containing trastuzumab, the patient with cachexia who was diagnosed with unresectable HER2-positive advanced gastric cancer showed improvement in the cachexia symptoms and the disappearance of lung metastasis.

A 64-year-old woman was diagnosed with Stage IV gastric cancer with lymph node and multiple liver metastases. She was treated with 6 courses of chemotherapy, in 3-week courses, with capecitabine (1,000 mg/m/(2)) plus cisplatin(80 mg/m(2)) administered for 2 weeks, followed by a drug-free week. She underwent curative total gastrectomy with D2 lymph node dissection and reconstruction by using the Roux-en-Y method. The postoperative pathological findings revealed a T3 (SE), N1M1, Stage II B tumor; the tumor was determined to be Grade 1b owing to the chemotherapeutic effect. Postoperatively, only S-1 therapy was administered, because of the development of Grade 3 hand-foot syndrome. The patient is alive 1 year and 8 months after the initial gastrectomy.

We report a case of gastric small cell carcinoma with liver and lymph node metastases responding to CPT-11 plus cisplatin (CDDP) chemotherapy. The patient was a 77-year-old woman with advanced gastric cancer, clinically diagnosed as P0H1M1CY0T4aN3. The immunostaining and pathological analysis of a biopsied specimen obtained during a gastrointestinal tract endoscopy indicated small cell carcinoma of the stomach. The patient received the following chemotherapy treatments: 11 courses of CPT-11 plus CDDP, 8 courses of docetaxel plus S-1, and 2 courses of paclitaxel. The patient is alive 2 years after the first chemotherapy treatment. We conclude that the combination of chemotherapy used was effective for treating the patient's small cell carcinoma of the stomach, which is considered to have a poor prognosis.

Purposes: The trastuzumab for Gastric Cancer study newly defined tumors that were positive for human epidermal receptor-2 (Her-2) and created a Her-2-oriented treatment strategy that is also applicable in the adjuvant setting for stage 2/3 cancers. However, there is currently no information available on the rate of Her-2 positivity and the relapse-free survival (RFS) stratified by Her-2 status in stage 2/3 patients., Methods: The Her-2 status, defined by the current standard method, was examined in 100 gastric cancer patients who underwent curative D2 surgery, who were pathologically diagnosed with stage 2/3 cancer, and received adjuvant S-1 chemotherapy between June 2002 and December 2011., Results: Ten of the 100 patients were Her-2 positive. Her-2-positive status was more frequently seen in tumors with a differentiated histology. The 5-year RFS rate was 56.3 % in Her-2-positive cases, and 48.8 % in Her-2 negative cases, which was not significantly different (P = 0.786)., Conclusions: The Her-2-positive rate for stage 2/3 gastric cancer patients was low, at only 10 %. Although the RFS was not significantly different based on the Her-2 status, the low positive rate made interpretation difficult. A multi-center study with a large sample size is necessary to clarify the prognostic impact of Her-2 in stage 2/3 gastric cancer patients.

Objectives: Concurrent chemoradiotherapy for regionally advanced stage III non-small cell lung cancer is the standard treatment method. However, the clinical implications of consolidation chemotherapy following chemoradiation have been unclear. Therefore, we conducted a phase II study of concurrent weekly carboplatin plus paclitaxel treatment in combination with radiotherapy followed by vinorelbine monotherapy. The primary endpoint was the 1-year survival rate., Patients and Methods: Chemonaive PS 0-1 patients with stage IIIA/B NSCLC were enrolled. During the concurrent chemoradiation phase, patients were treated with weekly paclitaxel 40 mg/m(2) plus carboplatin AUC 2. The primary tumor and involved nodes received 60 Gy in 2-Gy fractions over 6 weeks. During the consolidation phase, vinorelbine 25 mg/m(2) on days 1 and 8 was repeated for three cycles., Results: A total of 40 eligible patients (72.5 % male; median age, 63 years; range 29-74 years) were analyzed for efficacy. Squamous cell carcinoma was the most common histology (47.5 %), and more patients had clinical stage IIIB (55 %) cancer. The average radiation dose was 56.5 Gy, and the average number of carboplatin plus paclitaxel cycles was 4.93. Seventeen patients proceeded to the consolidation chemotherapy phase, and 14 completed three cycles of vinorelbine monotherapy. The objective response rate was 75.0 %, including 1 patient who achieved a complete response. Progression-free survival and overall survival (OS) were 46 weeks [95 % confidence interval (CI) 31-64 weeks] and 110 weeks (95 % CI 90-184 weeks), respectively. The OS rate at 1 and 2 years was 85.0 % (95 % CI 69.6-93.0 %) and 53.9 % (95 % CI 37.1-68.0 %), respectively., Conclusion: Concurrent chemoradiation with weekly carboplatin and paclitaxel followed by vinorelbine consolidation is effective for stage III non-small cell lung cancer and shows a generally mild toxicity profile.

Purpose: The aim of this study was to evaluate the safety and feasibility of gastrectomy after neoadjuvant chemotherapy in patients with gastric cancer., Patients and Methods: Forty-five patients received neoadjuvant chemotherapy and curative gastrectomy between December 2002 and May 2011. Surgical complications were evaluated according to the Clavien- Dindo classification., Result: The median age of the patients was 63 years. Twenty-three patients received a PTX and CDDP regimen, 20 received an S-1 and CDDP regimen, 1 received an S-1 regimen, and 1 received an CPT-11 and CDDP regimen as neoadjuvant chemotherapy. Distal gastrectomy was performed in 6 patients, and total gastrectomy was performed in 39 patients. The median operation time was 268 minutes, and the median blood loss was 249.5 mL. Complications more severe than grade 2 were observed in 10 patients: anatomic bleeding( grade 3a) was observed in 2 patients; abdominal abscess( grade 2), in 1 patient; and pancreatic fistula( grade 2), in 7 patients. No surgical mortality was observed., Discussion: The results of our study suggest that gastrectomy after neoadjuvant chemotherapy for the treatment of patients with gastric cancer is safe and feasible.

Here, we report the case of a patient with advanced gastric cancer complicated by pyloric stenosis and direct invasion into the pancreas who underwent curative resection after bi-weekly S-1/docetaxel(DS)therapy after gastrojejunostomy. A 73-year-old man consulted a general practitioner because of indigestibility, and upper gastrointestinal endoscopy indicated gastric cancer. He was referred to our hospital. Gastric cancer, whole stomach tumor(LMU), 150×80 mm, Type 3, T4a(SE), N2, M0, stage III B was diagnosed, and surgery was performed. The tumor was seen to directly invade the pancreas and the middle colic artery intraoperatively, so only a gastrojejunostomy was performed. After the operation, the patient was treated with DS therapy for 13 courses, and the response was defined as non-complete response(CR)and non-progressive disease (PD). During the second laparotomy, a curative operation was performed via distal gastrectomy because frozen-section diagnosis revealed that no cancer cells were present at the oral margin. Postoperatively, the tumor was diagnosed as LM, 10× 7 mm, 10×2.5 mm, pType 4, pT2(MP), pN0, pM0, CY0, stage I B. The patient is now receiving S-1 adjuvant chemotherapy and is still alive 2 years and 4 months after the first operation.

We report a curative resection of a case with advanced gastric cancer responding remarkably well to combination chemotherapy of docetaxel, cisplatin and S-1. The patient was a 71-year-old man with gastric cancer of Borrmann type 3 accompanied with N3. Staging laparoscopy revealed peritoneal dissemination. He was administered docetaxel intravenously at 40mg/ m2 on day 1, cisplatin intravenously at 60 mg/m2 on day 1, and S-1 orally at 80 mg/m2 on days 1 to 14. This treatment was repeated every 28 days as one course. According to gastroscope and CT findings, a significant tumor reduction was obtained after 4 courses. After 6 courses, a CT scan revealed partial response of the lymph node metastasis, and the serum CEA value was normalized. Curative total gastrectomy was performed. The histological effect of the primary lesion was judged to be grade 2. Combination chemotherapy of S-1, cisplatin and docetaxel can be effective and feasible for advanced gastric cancer.

Background: The regenerating gene Iα (REG Iα) is involved in gastric carcinogenesis as an antiapoptotic factor. Therefore, we investigated whether REG Iα confers resistance to chemotherapeutic drugs in gastric cancer (GC) cells and whether REG Iα expression is useful for predicting the response to chemotherapy and outcome in patients with GC., Methods: A total of 70 patients with unresectable stage IV GC received first-line chemotherapy with S-1 and cisplatin (S-1/CDDP). The expression of REG Iα was evaluated immunohistochemically using biopsy samples obtained before chemotherapy, and its relationship to clinicopathological parameters was analysed statistically. The effects of REG Iα gene induction on resistance to 5-FU or CDDP treatment were examined by cell survival assay and flow cytometry., Results: Of the 70 patients with unresectable stage IV GC, 19 (27%) were positive for REG Iα expression. The expression of REG Iα was independently predictive of poorer progression-free and overall survival in such patients (hazard ratio (HR) 2.46; P=0.002 and HR 1.89; P=0.037, respectively). The gene induction of REG Iα conferred resistance to cell death induced by 5-FU or CDDP in GC cells., Conclusion: In patients with stage IV GC, REG Iα, which confers resistance to chemotherapeutic drugs in GC cells, is a potential biomarker for predicting resistance to S-1/CDDP treatment.

Background/aim: This study assessed the toxicity and activity of biweekly docetaxel and S-1 combination therapy in elderly patients with advanced gastric cancer., Patients and Methods: One-hundred and thirteen patients were enrolled: 35 were 75 years old or more. The objective response rate, toxicity, progression-free survival (PFS), and overall survival (OS) were compared., Results: Dose reduction was significantly frequent in the elderly group (24/35 versus 25/78, p<0.001). The overall response rate was 54.9%. Out of these, 18 (15.9%) underwent gastrectomy (13 R0 gastrectomy). The median OS was 17.3 months and the median PFS was 8.0 months. Neutropenia was the most frequently observed hematological toxicity at grade 3 and 4 (34.5%), followed by leukopenia (24.8%). Most non-hematological toxicities were of grade 1 or 2. There were no significant differences in overall response rate, median OS, median PFS, or toxicities between the two groups., Conclusion: This combination offers favourable survival benefits with controllable tolerance for therapy of AGC in the elderly.

To establish a safe, long-term regimen of docetaxel (DOC) and cisplatin (CDDP) in an outpatient setting for gastric cancer refractory to S-1 adjuvant chemotherapy, a dose-escalating phase I study was conducted. Cohorts of patients were treated with escalating doses of DOC (starting at 20 mg/m² per week with 5 mg/m² increments) and a fixed dose of CDDP (25 mg/m²). Drugs were administered on days 1, 8, and 15. A cycle of this treatment was 28 days. In total, 52 courses were performed, and the mean number of courses was 5.3. Two of the four patients at dose level 3 showed dose-limiting toxicities (grade 4 neutropenia, and grade 3 anorexia and dehydration). The recommended dose (RD) of DOC was therefore defined as 25 mg/m². There is a need for a phase II clinical trial using this regimen in patients with S-1-refractory stage II/III gastric cancer.

The patient was a 31-year-old man with advanced gastric cancer, clinically diagnosed as ML, Less, Type 3, sig, cT3, cN0, cH0, cP0, cM0, cCY0, cStage IIA. He underwent D2 distal gastrectomy. On microscopic examination, tumor cells were detected in the distal margin of the resected stomach. After surgery, he received 1 course of S-1 followed by chemoradiation therapy(1.8 Gy×25, a total of 45 Gy) with 90 mg/m2 of paclitaxel and 40 mg/m2 of CDDP on days 1, 15, and 29 over 5 weeks. Subsequently, he received 5 cycles of S-1 chemotherapy. To date, no recurrence has been observed 5 years after surgery. This sequential therapy is an option to consider for enabling local and systemic control after gastric cancer surgery.

Background/aims: The outcomes of patients with scirrhous gastric cancer (SGC) remain poor. We retrospectively compared outcomes according to historically different treatments for SGC and studied the therapeutic usefulness of NAC with S-1 plus cisplatin followed by postoperative sequential chemotherapy., Methodology: We studied 93 patients with SGC. Between 1995 and 2000, 29 patients did not receive NAC and were instead given conventional anti-cancer drugs. Between 2000 and 2003, 20 patients received 4 weeks of NAC with low-dose cisplatin plus 5-fluorouracil (5-FU) followed by postoperative sequential treatment with new anticancer agents (neoadjuvant low-dose FP group). Between 2003 and 2006, 44 patients received 2 courses of NAC with S-1+cisplatin followed by postoperative sequential administration of new anticancer agents (neoadjuvant S-1+cisplatin group). Response rates and overall survival were compared among the treatment groups., Results: The rates of response to NAC were 15% in the neoadjuvant low-dose FP group and 36% in the neoadjuvant S-1+cisplatin group. Overall survival was significantly longer in the neoadjuvant S-1+cisplatin group than the other groups., Conclusions: Our results suggest that multidisciplinary therapy combining NAC with S-1+cisplatin and postoperative sequential administration of new anticancer drugs is therapeutically useful in patients with SGC.

Objectives: This study was conducted to determine the prognostic value of the Glasgow Prognostic Score (GPS), an inflammation-based prognostic score composed of C-reactive protein and albumin, for patients with advanced cancer., Methods: A total of 83 advanced gastric cancer patients receiving biweekly docetaxel/S-1 treatment (DS) were included in the study. To identify the value of GPS as prognostic factor for disease-specific survival (DSS) and progression-free survival (PFS), univariate and multivariate analyses were performed., Results: Unresectable tumors were observed in 78 patients and recurrent tumors were detected in 5 patients. Of these, 12 patients underwent gastrectomy. There were significant correlations between the GPS and the neutrophil/lymphocyte ratio. Univariate analysis revealed that the GPS, Eastern Cooperative Oncology Group performance status and gastrectomy after DS treatment significantly affected prognosis. Multivariate analysis showed that the GPS, age and gastrectomy independently influenced DSS, and that the GPS and gastrectomy also influenced PFS. Multivariate analysis restricted to patients without gastrectomy showed that the GPS and age independently affected DSS, and that the GPS influenced PFS., Conclusion: In the low GPS group, it may be possible to obtain favorable outcomes by chemotherapy in advanced gastric cancer patients. However, a well-designed prospective trial in a large patient cohort is required to corroborate the prognostic value of the GPS., (Copyright © 2012 S. Karger AG, Basel.)

In Japan, a one-year administration of S-1 is the standard adjuvant treatment for stage II/III gastric cancer after curative gastrectomy with a D2 lymph-node dissection.The treatment is recommended in the Japanese Guidelines for Treatment of Gastric Cancer(3rd Edition).Using data from results of a 5-year follow-up of the ACTS-GC trial, it was confirmed that using S-1 significantly improves the 5-year overall survival over surgery alone.However, the recurrence rate of stage III gastric cancer is still too high.More powerful treatment using multiple drugs is needed for this disease.This paper presents a new perspective for the development of post-operative adjuvant chemotherapy in the future, based on clinical trials recently reported.

Purpose: We evaluated the efficacy and toxicity of biweekly S-1 and docetaxel combination therapy in patients with advanced gastric cancer., Methods: Patients with histologically proven, unresectable advanced or recurrent gastric cancer, a performance status (PS) of 0-2 and no prior chemotherapy history were eligible for inclusion (n = 45). Patients received a total of 215 treatment courses (median, 4; range, 2-12) of S-1 oral administration twice daily for 1 week followed by a drug-free interval of 1 week. Docetaxel (40 mg/m(2)) was administered intravenously on days 1 and 15., Results: We observed 25 partial responses (55.6%) and one complete response (2.2%), resulting in an overall response rate of 57.8%. Twenty-four patients (53.3%) received second-line chemotherapy. Five patients (11.1%) underwent R0 gastrectomy during the course of the study. The median overall survival time was 15.3 months, the median time to progression was 6.9 months, and the median duration of response in 26 patients was 8.0 months. Neutropenia was the most frequently observed (40.4%) haematological toxicity at grades 3 and 4 and leucopenia was the second most common (29.8%). There were no treatment-related deaths., Conclusions: S-1 plus docetaxel combination therapy in an outpatient setting provided promising activity with acceptable adverse toxicities.

The clinical efficacy and safety of CPT-11+CDDP therapy were studied retrospectively in 34 patients with advanced and recurrent gastric cancer. The overall response rate was 5. 9%; MST was 209 days. The adverse effects observed were grade 3 in 7 patients(20. 6%). CPT-11+CDDP therapy could be useful and safe as third-line chemotherapy.

We report three cases of advanced gastric cancer successfully treated by combination therapy of S-1 and docetaxel (DOC). We administered S-1 orally at 80 mg/m² on days 1 to 7 and days 15 to 21, and DOC intravenously at 40 mg/m² on day 1 and 15, and evaluation was conducted every two courses. Case 1: A 73-year-old man with gastric cancer of cT4a, accompanied with bulky N2 lymph node metastasis, was treated with two courses of S-1 and DOC. Partial response was confirmed, followed by total gastrectomy, which revealed his histological grade to be 1b. Case 2: A 65-year-old man with gastric cancer of cT4a, accompanied with bulky lymph node metastasis, was treated with two courses of S-1 and DOC. Partial response was confirmed, followed by distal gastrectomy, which revealed his histological grade to be 1b. Case 3: A 76-year-old woman with gastric cancer of cT4b (panc), was treated with four courses of S-1 and DOC. After that, the main tumor was judged to be cT4a, followed by total gastrectomy, which revealed her histological grade to be 1b. Combined S-1 and DOC chemotherapy is an effective regimen for the treatment of unresectable gastric cancer.

A 70-year-old male patient had advanced gastric cancer with severe lymph node metastasis. He was treated by combination chemotherapy of S-1 120 mg/body (1-week administration and 1-week rest)and docetaxel (DOC) 40 mg/body( day 1 and 15). After 2 courses of treatment, the primary lesion was remarkably improved and para-aortic lymph nodes disappeared by CT scan, so we diagnosed it as a partial response (PR). Anemia (WHO grade 3) was observed as toxicity and treated with transfusion. This regimen could be performed on an outpatient basis for over 2 years, and the response was maintained on CT and endoscopic examination after 20 courses of treatment. The biweekly docetaxel and S-1 combination chemotherapy was thought to be an effective method as chemotherapy for an outpatient with advanced gastric cancer.

A 73-year-old man with gastric cancer of Borrmann type 3 accompanied with N3 was treated by combination therapy of S-1 and docetaxel (DOC). He received DOC intravenously at 45 mg/m/2 on day 1 and 15, and S-1 orally at 120 mg/body on day 1 to 7 and day 15 to 21. This treatment was repeated every 28 days as one course. After 4 courses of treatment, a CT scan revealed partial response of the lymph node metastases, and imaging modalities showed complete response of the primary lesion. The serum CEA value normalized after 4 courses of treatment. Toxicities included leukocytopenia (grade 3-4) and neutropenia (grade 3-4). Chemotherapy in the outpatient setting was possible by reduction of dose (DOC 45-->40-->35 mg/m2). Total gastrectomy was performed after 4 courses of treatment. The histological effect of primary lesion was judged to be Grade 2.

Background: Docetaxel and S-1 are novel antitumour chemotherapeutic agents with distinct toxicities. Here a phase I study of combined docetaxel and S-1 therapy for advanced gastric cancer is reported., Patients and Methods: The study group comprised 21 patients who received at least two courses of treatment. Intravenous docetaxel was administered with dose escalation from 20-45 mg/m2 depending on the dose-limiting toxicity (DLT) on days 1 and 15, and oral S-1 (BSA < 1.25 m2, 80 mg/day; 1.25 < or = BSA < 1.50 m2, 100 mg/day; 1.50 m2 < or = BSA, 120 mg/day) was administered on days 1-7 and 15-21., Results: The maximum tolerated dose of docetaxel was 45 mg/m2 and the DLT was defined as neutropenia. The recommended docetaxel dose was identified as 40 mg/m2. The response rate (including partial responses) was 57.1%. Five cases showed no change and four showed progressive disease after two courses of treatment. The mean survival rate was 15 months., Conclusion: A phase II clinical trial is required to confirm these results.

A 55-year-old man with advanced gastric cancer underwent total gastrectomy (T3N0M0, stage II , por, sig) in the USA. Following his return to Japan, the patient then suffered from a recurrence with ileus, bilateral hydronephrosis and ascites caused by peritoneal dissemination. Systemic chemotherapy of paclitaxel combined with 5-FU was performed, and after four cycles, ileus, bilateral hydronephrosis and ascites disappeared. S-1 monotherapy was started to maintain his QOL, but after five cycles, ileus of the transverse colon recurred. Colostomy was performed and systemic chemotherapy of paclitaxel combined with S-1 was performed. For 13 months, the patient's condition remained stable and he returned to society, but died 30 months after the first recurrence. This case suggests that paclitaxel-based chemotherapy is a promising treatment for gastric cancer with peritoneal dissemination.

The prognosis of a colorectal cancer patient with unresectable hepatic metastases is extremely poor. To improve the prognosis, when the hepatic metastases were initially unresectable, we performed second-look hepatectomy (s-l hepatectomy) after neoadjuvant hepatic arterial 5-FU infusion plus UFT (HAI-PMC). Here, we report the case of a sigmoid colon cancer patient with initially unresectable hepatic metastases showing a prolonged survival (6.5 years) by second-look operation after HAI-PMC. A 57-year-old woman was diagnosed with sigmoid colon cancer with unresectable liver metastases. Sigmoidectomy and hepatic arterial catheterization were performed in the initial operation, and HAI-PMC was performed 6 months after. Metastatic foci of the liver had shrunk (90.9%), but solitary metastatic lung cancer was detected during HAI. As no other metastatic lesion was observed, partial resection of the liver and lung was performed as a second-look operation, 6 months after the initial operation. The woman continued venous infusion chemotherapy as an outpatient, and she survived for 6.5 years after the initial operation. This result suggests that strategic multidisciplinary treatment utilizing s-l hepatectomy after neoadjuvant chemotherapy can lead to better prognosis for colorectal cancer patients with hepatic metastases.

A dose-escalation study was conducted for postoperative patients with stage IV gastric cancer to determine the recommended dose of daily intravenous cisplatin combined with a fixed dose of TS-1. TS-1 was administered orally twice daily for 2 weeks followed by a 1-week rest. The dose of TS-1 was based on the body surface area (BSA) as follows: 80 mg/day for BSA less than 1.25, 100 mg/day for BSA 1.25 to less than 1.50, and 120 mg/day for BSA 1.5 or more. Three dose levels of cisplatin (2, 4, 6 mg/m(2)) were studied, and two courses were performed. Cisplatin was infused on day 1-5 and 8-12 for 30 minutes. The National Cancer Institute common toxicity criteria (NCI-CTC Version 3) were used to evaluate the grade of toxicity. Three patients enrolled in each level. Dose escalation was performed when dose-limiting toxicities (DLT) were seen in 0/3, and 3 more cases of the same level were added when DLTs were seen 1-2/3. Maximum-tolerated dose (MTD) were determined when DLTs were seen in 3 cases. DLTs were not recorded during the administration of CDDP up to 4 mg/m(2). However, DLTs were seen 3/3 at level 3. From these results, cisplatin of 4 mg/m(2)was determined to be the recommended dose (RD) in this protocol for postoperative stage IV gastric carcinoma.

Purpose: Desmoid tumors are locally aggressive and can be fatal in familial adenomatous polyposis (FAP) patients if they are not suitable for surgery or radiation therapy. Here, we prospectively investigated the efficacy of a chemotherapeutic regimen involving doxorubicin (DOX) and dacarbazine (DTIC) for inoperable FAP-associated desmoid tumors., Patients and Methods: From an initial group of 120 FAP patients, seven of the 11 individuals with symptomatic unresectable desmoid tumors that were unresponsive to conventional hormone therapy were enrolled onto this study. The general chemotherapy regimen comprised four or five cycles of DOX (20 mg/m2 daily) plus DTIC (150 mg/m2 daily) throughout 4 days of drip intravenous infusion (day 1 through 4) every 28 days, followed by the cyclooxygenase-2 inhibitor meloxicam (10 mg/m2). The primary end point was relapse-free survival. The secondary end points included toxicity, clinical improvement, and tumor regression according to computed tomography., Results: Significant tumor regression was observed clinically and radiologically in all seven patients. Three patients showed a complete response. The average progression-free survival period was 74.0 months (range, 32.5 to 107.5 months). Three patients showed grade 3 adverse events with no treatment-related mortality. All seven patients survived and remained without tumor progression. An adenomatous polyposis coli germline-mutation analysis revealed no mutations in the specified regions., Conclusion: A chemotherapeutic regimen of DOX plus DTIC followed by meloxicam is an effective and safe treatment for FAP-associated desmoid tumors. This modality should be considered for use as first-line chemotherapy in symptomatic desmoid tumors that are unresponsive to conventional medical therapy, due to the absence of useful presymptomatic markers.

Background: To date, we have few effective chemotherapeutic agents against advanced and recurrent gastric cancer. 5-Fluorouracil (5-FU) and cisplatin (CDDP) are the most widely used drugs, and their combination has demonstrated favorable outcomes. However, the method (especially the timing) of CDDP administration is not well established., Methods: We examined the in-vitro effect of a combination of 5-FU and CDDP on four human gastric cancer cell lines: MKN-1, MKN-28, MKN-45, and MKN-74. The cell lines were exposed to 50% of the inhibitory concentrations of 5-FU and CDDP for 72 h and 8 h, respectively. CDDP was applied before, simultaneously with, and after the start of treatment with 5-FU., Results: When CDDP was applied after 5-FU, the cytotoxic activity against MKN-28, MKN-45, and MKN-74 was significantly potentiated. Against MKN-1, the earlier the initiation of CDDP treatment, the stronger was the cytotoxic effect., Conclusion: Our results suggest that the cytotoxicity of a combination of 5-FU and CDDP against human gastric cancer cells is both cell-line- and schedule-dependent and is especially affected by the timing of the CDDP treatment.

The combined effects of TNP-470 (TNP), a semisynthetic analogue of fumagillin, and 5-fluorouracil (5FU), a representative chemotherapeutic agent for colorectal cancer, were investigated using murine colon 26 adenocarcinoma (CT 26) cells. In a cell-proliferation study in vitro, 50% inhibitory concentrations (IC50) were determined to be 5.2 microg/ml and 240 ng/ml for TNP and 5FU, respectively. When CT 26 cells were treated with TNP and 5FU in combination, a remarkable cytotoxic effect was obtained. Isobologram analysis revealed synergism of these two agents in inhibition of the cell growth. In vivo, using a dorsal air sac assay, we found that TNP significantly inhibited the CT 26-induced angiogenesis. In addition, the combination of TNP and 5FU exerted a synergistic anti-tumor effect in a model of hepatic metastasis by portal injection of CT 26 cells. Since TNP is known to exert inhibitory effects on tumor cell growth through suppression of cell cycle progress from the G1 to S phases as well as neovascularization, it is speculated that the treatment with TNP enhanced the anti-tumor effect of 5FU through suppression of the cell cycle and tumor-derived angiogenesis. Taken together, these results suggest that combined treatment with TNP and 5FU is potentially useful for inhibition of tumor cell growth and liver metastasis of colorectal cancer.

A 3 Fr single lumen balloon catheter was successfully introduced for arterial infusion chemotherapy by percutaneous transfemoral arterial insertion. This balloon catheter was combined with a 6.3 Fr outer catheter coaxially. After placing the catheter into the target artery, the balloon was ruptured by injecting 1 ml of contrast medium. Alternatively, the balloon was made into a leaky balloon catheter by a small needle puncture before use. In 34 patients with liver tumors, we used this method combined with the continuous infusion of 5-fluorouracil for three to five weeks and once-a-week intra-arterial administration of mitomycin C and adriamycin. The result of this therapy was as follows: CR, 8.8%; PR, 29.4%; NC, 50.0%; and PD, 11.8%. No serious complications were encountered in our series except for some minor arterial problems caused by the catheter tip.

A case of sigmoid cancer with multiple liver metastases (S2PON3 + H3) who was treated by multi-modal treatment was reported. The multi-modal treatment is including intra-arterial administration of anti-cancer drugs as a pre-surgery treatment, intra-arterial infusion chemotherapy lasting for three to five weeks (three times), hyperthermia treatment combined with intra-arterial administration of anti-cancer drugs and intra-arterial expandable metalic stent. The patients lived for 2 years and 4 months in good condition.