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A 66-year-old male came to our hospital because of occult blood in stool and anemia. The patient was diagnosed as unresectable advanced gastric cancer,( ML/Less, type 2, tub2, cT4b[liver], cN+, cM0, cStage Ⅳ, HER2 negative). He was given oxaliplatin plus S-1 therapy. In the 3rd course of chemotherapy, he had severe anemia, and active bleeding from the tumor. To control the bleeding he underwent distal gastrectomy, lateral segmentectomy of the liver, and S4 partial hepatectomy. The patient underwent adjuvant chemotherapy with docetaxel plus S-1. Three months after surgery, lymph nodes recurrence was observed. He underwent second-line therapy with paclitaxel and ramucirumab. Seven months after surgery, lymph nodes recurrence was increased. He was switched to third-line therapy with nivolumab. He is currently arrive 12 months after surgery.

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.)

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.

Background: The C-reactive protein (CRP)-to-serum albumin ratio is associated with a poor prognosis in patients with several cancers. The purpose of this study was to clarify the relationship between the preoperative CRP/Alb ratio and overall survival of pancreatic ductal adenocarcinoma (PDAC) in patients who received radical surgery and S-1 adjuvant chemotherapy., Patients and Methods: We included 117 patients who underwent radical surgery with S-1 adjuvant chemotherapy. We constructed receiver operating characteristic curve (ROC curve) of the CRP/Alb ratio to determine the cut-off value. We analyzed the relationship among the CRP/Alb ratio, clinicopathological status, and survival., Results: The optimal cut-off value of the CRP/Alb ratio was 0.036. All patients were divided into a high-ratio group (CRP/Alb ratio ≥0.036) and low-ratio group (CRP/Alb ratio <0.036). The 5-year overall survival (OS) rates in the high- and low-ratio groups were 22.5% and 36.4%, respectively (p=0.0089). The 5-year disease-free survival (DFS) rates in the high- and low-ratio groups were 12.5% and 22.1%, respectively (p=0.0097). The univariate and multivariate analyses of the OS showed that the pathological N factor and CRP/Alb ratio were independent factors of the survival. The univariate and multivariate analyses of the RFS showed that the pathological N factor, resection margin, and CRP/Alb ratio were independent factors of the survival., Conclusion: The preoperative CRP/Alb ratio is a strong prognostic factor for PDAC patients with undergo curative resection with S-1 adjuvant chemotherapy., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

A 72-year-old man presented with right lower abdominal pain. Abdominal enhanced CT showed a large tumor in the ascending colon. Colonoscopyrevealed a type 2 tumor infiltrating three-quarters of the ascending colon. The biopsyspecimen showed a malignant lymphoma. Thus, the patient underwent ileocecal resection with D3 lymph node dissection. The histopathological diagnosis was primarydiffuse large B-cell lymphoma of the ascending colon. Post-operative PET-CT showed disseminated extra-nodal involvement, Stage Ⅳ(Lugano staging system). He was administered 2 courses of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy. However, the patient was diagnosed with progressive disease. He received several chemotherapies and finallydied 8 months after surgery. We report our present case and literature review.

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.

A 63-year-old man was admitted to our hospital for examination and treatment of a pancreatic head tumor detected at a nearby hospital. After CT, EUS-FNA, and PET-CT, he was diagnosed with unresectable pancreatic cancer with liver metastasis. After 9 courses of gemcitabine and nab-paclitaxel therapy, the primary tumor was dramatically reduced in size and the liver metastasis had disappeared. He underwent subtotal stomach-preserving pancreaticoduodenectomy. The postoperative diagnosis according to the General Rules of the Study of Pancreatic Cancer(7th edition)was Ph, TS1(15mm), adenosquamous carcinoma, ypT3, ypRP1, ypPL1, R0, ypN0(0/29), M0, CY0, ypStage ⅡA. The histological response was Grade 2. The patient remains alive without recurrence 5 months after surgical resection.

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.

Backgrounds: In Japan, standard regimens for advanced gastric cancer (AGC) include S-1 chemotherapy. The standard treatment for early relapse after adjuvant chemotherapy with fluoropyrimidine alone is platinum-based chemotherapy, while the standard treatment for early relapse after adjuvant chemotherapy with fluoropyrimidine plus platinum is second-line chemotherapy. To evaluate the efficacy and safety of capecitabine plus cisplatin (XP) treatment for AGC patients who relapse within 6 months after S-1-based therapy, we conducted a multicenter phase II trial (NCT01412294)., Methods: HER2-negative gastric cancer patients treated with adjuvant chemotherapy including S-1 for more than 12 weeks and relapsed within 6 months were treated with capecitabine 1000 mg/m 2 bid for 14 days plus cisplatin 80 mg/m 2 on day 1 of a 3-week cycle. The primary endpoint was PFS; secondary endpoints were OS, time to treatment failure, overall response rate (ORR) and safety., Results: Forty patients (median age 64) were enrolled; of those, 37 (92.5%) received adjuvant S-1 monotherapy. Median PFS was 4.4 months (95% CI 3.6-5.1), which was longer than the 2-month protocol-specified threshold (p < 0.001). Median OS was 13.7 months (95% CI 9.0-17.7) and ORR was 8/30 (26.7%) (95% CI 14.2-44.4). Most common grade ≥ 3 adverse events were neutropenia (23%), anemia (18%), elevated serum creatinine (18%), fatigue (13%), diarrhea (7.5%), and anorexia (7.5%)., Conclusions: XP was safe and effective in patients with early relapse after S-1 adjuvant chemotherapy for curatively resected gastric cancers. XP may be a good option for the treatment of patients after early failure after adjuvant S-1., Trial Registration: NCT01412294.

Background: Capecitabine plus cisplatin (XP) is a standard global regimen, while S-1 plus cisplatin (SP) is a Japanese standard for first-line treatment of advanced gastric cancer (AGC). We conducted a phase II trial comparing XP with SP for patients with AGC to confirm whether these regimens can be used as controls in a phase III study and to explore whether histological subtypes favour XP or SP., Patients and Methods: Eligible patients were randomised to receive either S-1 40 mg/m 2 for 21 days plus cisplatin 60 mg/m 2 (q5w) or capecitabine 1000 mg/m 2 for 14 days plus cisplatin 80 mg/m 2 (q3w). The primary end-point was progression-free survival (PFS). The secondary end-points were overall survival (OS), overall response rate (ORR) and safety., Results: In 110 eligible patients, 24-week PFS was higher in both groups (SP 50.9%, XP 43.5%) than the protocol-specified threshold of 40%. The median PFS for SP versus XP was 5.6 and 5.1 months (hazard ratio [HR], 1.126; p = 0.5626); OS was 13.5 and 12.6 months (HR, 0.942; p = 0.7769) and the ORR was 42.4% and 69.4% (p = 0.0237), respectively. The most common grade ≥3 adverse events with SP/XP were anaemia (16%/20%), neutropenia (9%/18%) and anorexia (18%/13%). Subgroup analysis by histological classification showed no statistical difference between treatments., Conclusions: XP and SP are comparable and can be recommended as control arms in a phase III study for AGC. Histological subtypes were not sensitive markers for the selection of XP or SP., Clinical Trial Registration: NCT00140624., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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.

We report the case of a 69-year-old man diagnosed with gastric cancer.The patient underwent distal gastrectomy(D2) and Billroth I reconstruction in March, 2010. Postoperative histopathological examination indicated M, Ant, Type 5, 100×50 mm, pap>por2>sig, T4aN3M0, pStage III C.We performed S-1 therapy as adjuvant chemotherapy.Abdominal CT showed para-aortic lymph node recurrence in February, 2015. Since HER2 protein was overexpressed in primary tumor immunostaining, he was treated with capecitabine plus CDDP plus trastuzumab therapy.After the chemotherapy, CEA levels decreased to the normal range and the enlarged lymph node was remarkably decreased in size in May, 2015.T he patient is alive 24 months after the chemotherapy with no evidence of recurrence.

We describe 4 cases of locally advanced colorectal cancer resected successfully after neoadjuvant chemotherapy(NAC) conducted between April 2015 and August 2016. The NAC with mFOLFOX6 plus bevacizumab was performed after ileostomy for prevention of obstruction, because of tumor invasion into other organs. After chemotherapy, we could perform resection and avoid invasive surgery in either cases.

A 75-year-old man admitted for left lateral abdominal pain was found to have advanced poorly differentiated gastric adenocarcinoma with abdominal para-aortic and Virchow's lymph node metastases, which was diagnosed to be clinical Stage IV (T3N3H0M1[LYM]). As curative surgery was not deemed possible, we started chemotherapy administration using S-1 (120mg/day)administered orally for 3 weeks and cisplatin(CDDP 100mg/body)administered intravenously on day 8. After 6 courses of chemotherapy, a CT scan showed that all lymph nodes metastases had disappeared, resulting in downstaging to clinical Stage II (T3[SE]N0H0P0M0). Thus, we performed total gastrectomy, lymph node dissection(D2), and splenectomy. Histological findings showed no residual tumor cells in any of the lymph nodes. However, cancer cells remained in the primary gastric lesion. The pathological response to chemotherapy was judged to be Grade 2. The patient has been recurrence-free for 5 years after 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.

Adrenal metastasis from colorectal cancer occurs in the presence of multiple synchronous metastases at other sites. We report a case of heterochronous solitary adrenal metastasis from rectal cancer. A 55-year-old man underwent anterior resection with D3 lymph node dissection for rectal cancer. The pathological stage of the tumor was III b, and adjuvant chemotherapy with mFOLFOX6 was administered for 6 months. Eighteen months after surgery, abdominal computed tomography(CT) revealed right solitary adrenal metastasis. His tumor marker levels were considerably elevated; therefore, he received preoperative chemotherapy with FOLFIRI plus bevacizumab(BV). After preoperative chemotherapy, his tumor marker levels decreased, and CT and FDG-PET/CT did not uncover any other metastatic lesions. The patient was diagnosed with solitary adrenal metastasis, and right adrenalectomy was performed. Histological examination confirmed the tumor to be adrenal metastasis from rectal cancer, and the histopathological Grade was 2. The patient received adjuvant chemotherapy with mFOLFOX6, and he is alive 7 months after adrenalectomy without evidence of recurrence. Adrenalectomy is recommended for solitary adrenal metastasis from colorectal cancer. Additionally, adrenalectomy after preoperative chemotherapy is an effective strategy for patients with solitary adrenal metastasis and high tumor marker levels.

We report a case of advanced esophageal and gastric cancer that was successfully treated via multimodal therapy. A 65- year-old man with hoarseness was referred to our hospital. He was diagnosed with clinical T4aN2M0, Stage IV esophageal squamous cell carcinoma and clinical T3N1M0, Stage II B gastric adenocarcinoma. He was treated with 3 courses of chemotherapy, administered over 4weeks, with S-1(80mg/m / / 2: day 1-14), cisplatin(60mg/m2: day 1), and docetaxel(40mg/m2: day 1). Computed tomography(CT)revealed shrinkage of the primary esophageal tumor, gastric tumor, and lymph node metastases. Next, we selected definitive radiation chemotherapy(CRT), because lymph node metastases remained around the bilateral recurrent laryngeal nerves. After CRT with a total 60 Gy plus administration of 5-fluorouracil and cisplatin, CT showed that the primary esophageal tumor and lymph node metastases had disappeared. Then, distal gastrectomy was performed for the remaining gastric cancer, as part of the multimodal therapy. After gastrectomy, no systemic chemotherapy was performed. At a follow-up examination 5 years and 6 months after the start of chemotherapy, the patient is alive without recurrence.

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 71-year-old man was diagnosed with gastric cancer (LM, Less, type 2, T4aN2M0, cStageⅢb). A diagnostic laparoscopic surgery revealed serosal invasion without peritoneal dissemination. Two courses of neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer using DCS (DTX: 20 mg/m2 on day 1, CDDP: 50 mg/m2 on day 1, S-1: 120 mg/day, twice a day on days 1-14) was performed, which resulted in a clinical partial response. Consequently, distal gastrectomy with D2 lymph node dissection, and BillrothⅠreconstruction were carried out. Histopathological examination revealed no residual cancer cells both in the primary lesion and in the lymph nodes, indicating a pathological complete response (grade 3). Six courses of S-1 (120 mg/day on days 1-28, followed by 2 weeks of rest) were administered as adjuvant chemotherapy. At the 2 years 10 months follow-up after adjuvant therapy, the patient has had no recurrence. Combination chemotherapy with NAC-DCS can be a safe and effective regimen for locally advanced gastric cancer.

A 77-year-old man underwent total gastrectomy with D1+ lymph node dissection after being diagnosed with cT4aN2M0, cStage ⅢB gastric cancer. Peritoneal dissemination was detected in the bursa omentalis. The pathological diagnosis after surgery was pT4aN3b (21/41) M1 (P1). He was treated with 6 courses of S-1 chemotherapy. Two years after surgery, upper gastrointestinal endoscopy revealed the presence of a tumor in the mid-thoracic esophagus. It was diagnosed to as metastatic esophageal cancer and treated with combination chemotherapy consisting of docetaxel (25 mg/m2, days 1, 8, 15) and cisplatin (25 mg/m2, days 1, 8, 15) in a 28-day cycle. A clinically complete response was observed after 5 courses of chemotherapy. Currently, the patient is alive with no signs of recurrence 12 months after the initial recurrence.

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.

We report a case of gastric carcinoma with metastasis to the liver responding to surgery and chemotherapy.The patient was a 74-year-old man with gastric cancer, clinically diagnosed as P0H0M0T3N0.We initially planned to perform an open distal gastrectomy.However, intraoperative findings revealed metastatic tumors in the liver.Therefore, the patient underwent a D1 distal gastrectomy.After surgery, the patient received the following chemotherapy regimens: 1 course of S-1 and 8 courses of a S-1 and cisplatin (CDDP) combination.After 8 courses of S-1 plus CDDP treatment, liver metastases could not be detected by computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET). The patient was assessed to have a clinical complete response.Fifty months after surgery, the patient is alive without recurrence.

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.

A 45-year-old man was transferred to our hospital because of advanced gastric cancer and peritoneal dissemination. After he received an S-1 plus cisplatin( CDDP) regimen for 6 courses, the primary lesion and ascites had disappeared. However, the primary lesion recurred, and he underwent treatment with 16 courses of an S-1 plus docetaxel regimen. He subsequently developed peripheral neuropathy, and was switched to the irinotecan (CPT-11) regimen. As he experienced appetite loss, it was impossible to continue the chemotherapy. Therefore, he underwent a salvage surgery and an R0 resection was performed. However, 9 months after the surgery, he experienced paraaortic lymph node recurrence and peritoneal dissemination. The patient died 13 months after the surgery.

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.

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.

In adenocarcinoma of the small intestine, delays in diagnosis are frequent. The majority of patients present with advancedstage disease, and have either lymph node involvement or distant metastatic disease. Surgical resection is a mainstay in treatment of this disease, and the effectiveness of chemotherapy for advanced-stage or metastatic disease has been reported. We report a case of adenocarcinoma of the small intestine surviving for many years after surgical resection and chemotherapy. A 47-year-old woman underwent a small intestine resection, because she had a small intestinal tumor with obstruction. Histopathological examination revealed moderately-differentiated adenocarcinoma with lymph node metastasis. Adjuvant chemotherapy with S-1 was administered for a year, but in March 2006, a recurrent lesion at the right ovary was detected, and she underwent right adnexectomy. Because the ascites cytology revealed class V, chemotherapy was administered. In December 2008, CA19-9 elevated and magnetic resonance imaging showed a tumor behind the uterus, which was diagnosed as a recurrent disease. Because the tumor invaded the rectum, she received a low anterior resection, hysterectomy, and left adnexectomy. After surgical resection, UFT/UZEL was administered for half a year. In July 2010, computed tomography showed multiple lung metastases, and chemotherapy was performed again. However, the regimen was changed because her tumor marker elevated. She is being treated using a combination of cisplatin and irinotecan.

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.

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.

Purpose: As a project of the Kanagawa Colorectal Cancer Study Group, we performed this study to analyze the efficacy and the safety of modified FOLFIRI (irinotecan: 150 mg/m2) therapy for Japanese patients with metastatic colorectal cancer., Patients and Methods: We treated PS 0-1 Japanese patients with measurable or assessable colorectal cancer who either had not received preliminary treatment, or were postoperative with metastasis and had undergone radiation therapy or adjuvant chemotherapy before more than four weeks, and further had provided written acceptance of our proposed procedures. Twenty patients received modified FOLFIRI therapy as a 2-hour infusion of CPT-11 150 mg/m/2 and l-LV 200 mg/m2 followed by a bolus 5-FU 400 mg/m/2 and 46-hour infusion 5-FU 2, 400 mg/m2. Tumor response was assessed by RECIST and toxicity by NCI-CTC., Results: Thirty males and seven females underwent an average 10 courses of treatment. This therapy achieved a 50% response rate, 80%disease-control rate, and 316+/-40 days PHS. Regarding hematological toxicity, 11 patients (55%) experienced leukemia, which developed to grade 3/4 in 5 (25%) of them. Twelve patients (65%) experienced neutropenia, which developed to grade 3/4 in 10 (50%) of them. Digestive toxicity was observed in 16 patients (80%), which developed to grade 3/4 in only one patient (5%) with gastric ulcer. Six patients (30%) experienced alopecia, which was grade 1/2 only., Conclusion: This clinical study was safely carried out. The efficacy was as good as in previous reports using a regular dose of CPT-11.

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.

In May 2006, a 79-year-old man underwent left colectomy and D2 lymphadenectomy for descending colon cancer (fStage II , Cur A). No adjuvant chemotherapy was done. Eighteen months after surgery, the serum tumor marker level was increased (CA19-9 526 U/mL), and multiple liver metastases (H2) and peritoneal dissemination were detected using abdominal CT. He was treated with S-1 plus CPT-11 therapy, because mFOLFOX6 as a standard chemotherapy for advanced colorectal cancer was rejected. After 4 courses, tumor markers normalized and abdominal CT revealed a partial response. At present, progression-free survival (PFS) is 240 days. In our case, this regimen was found to be convenient and safe in an outpatient compared with FOLFIRI and FOLFOX. This case suggested that S-1 plus CPT-11 therapy could well be a promising systemic chemotherapy for patients with advanced colorectal cancer.

We report a case of small cell carcinoma of the esophagus(SCEC)treated by chemotherapy with 5-fluorouracil(5- FU)plus cisplatin(CDDP)and operation. A 60-year-old man was seen at the hospital because of a sensation of food sticking in his throat at meals. Gastrointestinal endoscopy revealed a type 2 tumor in the middle portion of the esophagus, which was pathologically diagnosed as small cell carcinoma. With a diagnosis of SCEC, preoperative chemotherapy with 5-FU plus CDDP was given. Primary lesion showed complete response. After chemotherapy, an operation was performed. The tumor had histopathologically disappeared, and the patient has been free of any signs of recurrence, as of 6 years 2 months after the operation. Primary small cell carcinoma of the esophagus is a rare disease with early systemic metastasis, and the prognosis remains poor. In a review of the literature, all patients with SCEC who had survived for 2 years or more had undergone combined therapies including operation, chemotherapy and radiotherapy. This study deals with a long-term surviving patient without any signs of recurrence after excision of the foci followed by chemotherapy.

A 74-year old man was treated with first-cycle chemotherapy of paclitaxel (70 mg/m2=110 mg day 1, 8, 15) and carboplatin (AUC5=500 mg day 1) for lung cancer (c-T3N2M0, stage III A). On day 6 abdominal pain appeared, while on day 7 abdominal CT showed a perforation of the digestive tract. Thirty-three hours after the onset he underwent Hartmann operation during which we recognized a perforation 1.7 cm in size in the rectum. Although the cause of the perforation was unknown from the pathological findings, anticancer agents were suspected to be involved. Perforation should be taken into consideration in connection with acute abdominal disease after chemotherapy.

The cytotoxic effect of trastuzumab in combination with oral fluoropyrimidine S-1 on human epidermal growth factor receptor 2 (HER2)-overexpressing human pancreatic cancer cell line TRG in vitro and in vivo was investigated. HER2 expression in TRG was analyzed by RT-PCR and flow cytometry. For in vitro experiments, 5-fluorouracil (5-FU) was used instead of S-1. In vivo studies were conducted with TRG xenografts in athymic mice. Trastuzumab (10 mg/kg) was administered intraperitoneally once a week for 4 weeks. S-1 (10 mg/kg) was administered orally 5 days a week for 4 weeks. The results showed that TRG cells were positive for HER2 mRNA and overexpressed HER2 protein. Either trastuzumab or 5-FU concentration-dependently inhibited the growth of TRG cells. The combination of trastuzumab and 5-FU resulted in a significant inhibition of growth of TRG cells compared to either agent alone (P<0.001). Incubation of TRG cells with peripheral blood mononuclear cells after treatment with trastuzumab enhanced the antiproliferative effect of trastuzumab, which could be the result of antibody-dependent cellular cytotoxicity. The combination of trastuzumab and S-1 resulted in a significant reduction in xenograft volume compared to each agent alone (P<0.0001). In conclusion, this study showed that combination therapy with trastuzumab and S-1 may be effective for HER2-overexpressing pancreatic cancer patients.

We treated two patients in whom irinotecan (CPT-11)+cisplatin (CDDP) and irradiation showed efficacy against brain metastases of gastric cancer. CPT-11 and CDDP were administered on days 1 and 15 of a 28-day cycle at 60 mg/m(2) and 30 mg/m(2), respectively. The first patient was a 63-year-old man,who complained of headache and weakness. In March 2003, he was diagnosed as having Stage IV gastric cancer with peritoneal dissemination (T3, Nx, P1) and underwent total gastrectomy with D1 dissection. Chemotherapy with S-1 was continued after surgery. Two years and two months later, a metastatic tumor was found in the upper lobe of the right lung. The protocol was changed to S-1+CDDP, but progression of his disease occurred. The weekly paclitaxel (PTX) therapy was tried instead. Seven months later, he developed headache and weakness, and multiple brain metastases were diagnosed by CT scanning. We performed total brain irradiation (30 Gy) and started CPT-11+CDDP therapy, which was continued on a fortnightly basis at 60 mg/m(2) and 30 mg/m(2), respectively. The brain metastases regressed (PR), and this therapy led to a marked improvement in his quality of life. The second patient was a 78-year-old man, who complained of weakness of the lower extremities and dizziness. In November 2003, he was diagnosed as having stage IB gastric cancer (T2 (ss), N0, P0), and underwent total gastrectomy and splenectomy with D2 dissection. One year and four months later, local recurrence at the anastomosis was detected, as well as a metastatic tumor in the right lung. S-1, S-1+CDDP, and weekly PTX therapy were all tried. One year later, the patient was admitted with weakness and dizziness,and brain metastases were detected by CT scanning. We then performed Cyber Knife treatment and administered CPT-11+CDDP. As a result, his brain metastases partially regressed (PR).

Background: S-1 is a novel oral fluorouracil antitumor drug that contains a combination of 3 pharmacological agents: tegafur (FT), a 5-fluorouracil (5-FU) prodrug, 5-chloro-2,4-dihydroxypyridine (CDHP), which inhibits the activity of dihydropyrimidine dehydrogenase (DPD), and potassium oxonate (Oxo), which reduces the gastrointestinal toxicity of 5-FU. S-1 and docetaxel have both been identified as effective agents for the treatment of gastric cancer. However, little is known about the effects and/or adverse effects of a combination of these drugs in the treatment of gastric cancer. The aim of this phase I study was to determine the maximum-tolerated dose (MTD) and the recommended dose of docetaxel with a fixed dose of S-1 in patients with advanced or recurrent gastric cancer., Patients and Methods: Patients with metastatic, recurrent, or unresectable gastric cancer received docetaxel at a starting dose of 25 mg/m2 by i.v. infusion over 1 h on days 1, 15 and 29, and S-1 at the full dose of 80 mg/m2 daily for 4 weeks of every 6 weeks. Nine patients were treated with increasing dosages of docetaxel as follows: (docetaxel/S-1, mg/m2): 25/80 (level 1), 30/80 (level 2) and 35/80 (level 3). All cases were assessable for drug safety and 7 were assessable for response. Colony-stimulating factor (CSF) was not used in this study. The adverse effects of treatment were analyzed according to NCI-CTC, version 2 and the response was assessed according to the Japanese Classification of Gastric Cancer, 13th Ed., Results: The MTD was reached at the 35/80 mg/m2 dose-level in 3 out of 3 patients. These patients experienced some dose-limiting toxicity (DLT) or grade 3 anemia. The reported DLTs included diarrhea, stomatitis and general fatigue. Due to these results, 3 additional patients were not enrolled at this dose-level. No hematological or non-hematological adverse effects (more severe than grade 2) were observed in any of the level 1 or 2 patients. However, among the level 1 patients, 66.7% developed grade 2 leukocytopenia and 33.3% developed grade 2 neutropenia. Among the level 2 patients, 33.3% developed grade 2 appetite loss, diarrhea and general fatigue. Partial responses were achieved in 3 (42.9%) out of the 7 patients with evaluable lesions. These results indicated that the appropriate doses of the 2 drugs in combination therapy are 30 mg/m2 for docetaxel and 80 mg/m2 for S-1., Conclusion: The S-1/docetaxel drug combination showed a good safety profile, with diarrhea and general fatigue being common, but manageable, adverse reactions. Moreover, the responses observed in this study suggest that the drug combination shows a high degree of efficacy in patients with advanced and/or recurrent gastric cancer.

A patient was a 66-year-old male who had advanced gastric cancer with left gastric artery lymph node metastasis and invasion of pancreas and spleen. We thought a complete resection was difficult, so he was given neo-adjuvant chemotherapy by combined of TS-1 100 mg/day (2 weeks administration and 1 week rest) and Paclitaxel (PTX) 75 mg/body (day 1, 8). After 2 courses of this neo-adjuvant chemotherapy, tumor and lymph node swelling had decreased in size, and the tumor markers were reduced remarkably (CEA 9 2.5 --> 12.2 ng/ml, CA 19-9 2, 739 --> 19 3 U/ml). He underwent total gastrectomy and Roux-en Y reconstruction. No.4 d and No.7 lymph nodes were swollen and hard, but white with a neurotic-like appearance. On pathological study, no malignancy was seen in the lymph nodes, and a good partial response was achieved. In this chemotherapy, no side effects were seen, and he maintained good quality of life. TS-1/PTX therapy was thought to be an effective neoadjuvant chemotherapy for advanced gastric cancer.

The aim of this study was to evaluate the efficacy and toxicity of 5-fluorouracil (5-FU) and l-leucovorin (l-LV) given at the same dose intensity and administered monthly (given weekly for 3 weeks followed by a week of rest; arm A) or every 2 months (given weekly for 6 weeks followed by 2 weeks rest; arm B) to patients with advanced colorectal carcinoma. The dose of 5-FU was 500 mg/body or 750 mg/body, with an average dose of 432.8 mg/m2. A total of 7 institutions participated in this multi-center study and were randomly divided into 2 groups of arms A and B. Thirty-three patients were entered into arm A and 21 into B. The overall response rate was significantly (p = 0.007) greater in arm B (23.5%) than in arm A (0%). The most frequently observed toxicity was diarrhea, which was observed in 6.5% of arm A and in 33.3% of arm B, marking a significant difference (p = 0.034). These data suggest that a monthly 5-FU/l-LV regimen might be less toxic than a 2-months regimen and less effective at the dose given as above. Further study is needed to evaluate the efficacy of a monthly regimen.

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.

A 71-year-old woman presented with an abdominal mass and ascites and was subsequently admitted to our hospital in June 1995. Further examination revealed that the mass was malignant and, as a result, surgery was indicated. However, the mass demonstrated widespread peritoneal dissemination, which therefore could not be resected, and pathological findings suggested a malignant peritoneal mesothelioma. The patient showed a remarkable response to combined chemotherapy with an accompanying intraperitoneal injection of cisplatin and etoposide and an intravenous injection of caffeine. However, owing to side effects, this regimen was discontinued. The patient was administered a combination drug of uracil and tegafur (UFT) in addition to intraperitoneal injection of cisplatin as an outpatient. By the 223rd day after surgery, the tumor mass and ascites had completely disappeared according to the CT. Hence chemotherapy was judged to have resulted in complete remission. Such a marked response to chemotherapy is rare in an advanced malignant peritoneal mesothelioma such as the present case. Eight months later, the tumor recurred in the pleura. Another regimen of chemotherapy with cisplatin and CPT-11 was performed. However, this treatment proved ineffective. The patient subsequently died of respiratory failure in January 1997 due to the mesothelioma. This is a case report of complete remission of malignant peritoneal mesothelioma by combined chemotherapy.

The combination effect of 5-fluorouracil (5-FU) and cisplatin was examined in terms of the proliferation, morphology and expression of Ki-67 antigen, and propidium iodide (PI) staining using four cultured human gastric cancer cell lines, and we assessed how such activity was affected by the exposure time and the timing of treatment. MKN-1, MKN-28, MKN-45 and MKN-74 cells were exposed to various concentrations of 5-FU for 72 h and cisplatin for 8 or 72 h. At IC50, MKN-28 cells were more sensitive to 5-FU than other cell lines, whereas MKN-1 and MKN-45 cells were more sensitive to cisplatin than other cell lines. The cell growth-inhibitory activity of cisplatin was found to be 'area under the curve' dependent. When 5-FU and cisplatin were combined simultaneously, the combination effect was higher than that of 5-FU or cisplatin alone. On the other hand, when cisplatin was applied before 5-FU, there was no potentiation of the cell growth-inhibitory activity by combination treatment. In 5-FU-treated MKN-74 cells, the size, morphology and PI staining of nuclei were almost the same as those of the untreated cells, and the expression of Ki-67 antigen was less than that of the untreated cells. In cisplatin-treated MKN-74 cells, the size of cells and nuclei was larger than that of the untreated cells and fragmentation of nuclei was observed. The expression of Ki-67 antigen was less than the untreated cells but more than that of 5-FU-treated cells. In the cells treated with 5-FU and cisplatin in combination, the above changes were an intermediate of those of 5-FU-treated cells and cisplatin-treated cells. In conclusion, the cell growth-inhibitory activity of 5-FU and cisplatin against gastric cancer cells was potentiated by the combined treatment with 5-FU and cisplatin simultaneously, but not with cisplatin followed by 5-FU.

We encountered a rare case of postbulbar ulcer caused by adjuvant chemotherapy after gastrectomy. A 64 year-old woman, who received chemotherapy with CDDP-5-FU after gastrectomy, developed severe hematemesis. Endoscopic examination revealed a gigantic ulcer at the anal site of Vater's papilla. The ulcer was healed with PPI and soft diet.

We performed combination chemotherapy consisting of 5-FU, leucovorin, and CDDP (FLP therapy) against noncurative resected or recurrent stomach cancer in outpatients as of August 1991. Seventeen outpatients patients underwent FLP therapy until February 1993. Therapeutic responses, survival time after the operation or recurrence, rate at home, and the improvement of performance status (PS) were studied. The response rate was 54.5%, median survival time was 410 days, the rate at home was 75.5 +/- 14.7%, and the rate of improvement of PS was 82.4%. Toxicities were observed in 70.6%. Thrombocytopenia must be followed carefully, but it was encountered in only a few patients. FLP therapy for advanced or recurrent stomach cancer in outpatients was expected to improve the QOL.