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Enteral nutrition has been reported to be safe and effective in malnourished patients undergoing upper gastrointestinal surgery. In this study, we devised night home enteral nutrition (N-HEN) as a novel nutritional strategy and evaluated the efficacy in gastric cancer patients following total gastrectomy. Between January 2017 and March 2021, 24 patients were prospectively included in the protocol and supported by N-HEN for three postoperative months through a jejunostomy during the night (Elental:1200 kcal/day), and 22 patients without N-HEN were followed as a control group (CG). Body weight loss, nutritional indicators and tolerance to chemotherapy were evaluated. After 3 and 6 months, patients with N-HEN had significantly less body weight loss than CG (3 months P < 0.0001: N-HEN 4.0% vs. CG 15.2%, 6 months P < 0.0001: N-HEN 7.7% vs. CG 17.7%). Prealbumin was significantly higher in patients with N-HEN than CG after 3 and 6 months (3 months P < 0.0001, 6 months P = 0.0037). Albumin, total protein and hemoglobin, tended to be higher after 3 and 6 months in patients with N-HEN than CG, and total cholesterol after 6 months. Concerning the tolerance to adjuvant chemotherapy in Stage II-III patients, patients with N-HEN significantly had a higher completion rate (P = 0.0420: N-HEN 70% vs. CG 29%) and longer duration (P = 0.0313: N-HEN 458 days vs. CG 261 days) as planned. Continuous monitoring of blood glucose concentration in patients with N-HEN did not show nocturnal hypoglycemia or hyperglycemia. N-HEN could be a novel enforced and physiologically effective nutritional strategy to support potentially malnourished patients following total gastrectomy., (© 2022. The Author(s).)

Background: Preclinical studies have shown that mitomycin C (MMC) acts synergistically with irinotecan (CPT-11). In this phase II study, we evaluated the efficacy and toxicity of MMC/CPT-11 therapy as second-line chemotherapy for patients with fluoropyrimidine-resistant advanced gastric cancer., Methods: Eligible patients had evidence of tumor progression despite prior treatment with fluoropyrimidine-based regimens or had relapsed within 6 months after completion of therapy with adjuvant fluoropyrimidines. Treatment consisted of MMC (5 mg/m(2)) and CPT-11 (150 mg/m(2)) administered i.v. every 2 weeks. The primary endpoint was the response rate (RR). Our hypothesis was that this combination therapy was efficacious when the lower boundary of the 95% confidence interval (CI) of the RR exceeded 20% of the threshold RR., Results: Between April 2002 and July 2003, 45 eligible patients were registered and analyzed. Among the 45 patients, 40 (89%) had previously received chemotherapy for metastasis and 24 (53%) had a performance status (PS) of 0. Thirteen partial responses were obtained among the 45 patients, resulting in an overall RR of 29% (95% CI, 16-42%). The median time to progression was 4.1 months, and the median survival time was 10 months, with a 1-year survival rate of 36%. Grade 4 neutropenia was observed in 29% of the patients, whereas febrile neutropenia occurred in 9%. The incidence rates of grade 3 nausea and diarrhea were 13 and 2%, respectively., Conclusions: Although this study did not achieve the per-protocol definition of activity, the progression-free survival and overall survival appeared to be promising, with acceptable tolerability. Thus, MMC/CPT-11 therapy as second-line chemotherapy for fluoropyrimidine-resistant advanced gastric cancer presents a potential treatment option in patients with a good PS.

Objectives: To carry out a phase II multi-center study on the efficacy and safety of triple combination therapy with paclitaxel, S-1, and cisplatin in patients with unresectable/metastatic gastric cancer., Methods: A total of 63 patients from 8 institutions were included in this study. Paclitaxel (160 mg/m²) was administered by infusion for 3 h on the first day. S-1 (70 mg/m²/day) was administered orally for 14 consecutive days from the first day. Cisplatin (60 mg/m²) was administered intravenously over 24 h on day 14 of every 28-day cycle., Results: All 63 patients were assessed for clinical efficacy and safety. A total of 259 cycles of treatment were administered (median 4, range 1-10). Grade 3-4 toxicities included neutropenia in 30.2%, thrombocytopenia in 12.7%, and anemia in 11.1%. There was no grade 3-4 non-hematological toxicity or treatment-related death. Complete response was observed in 6 patients and partial response in 34 patients. The overall response rate was 63.5%. The median progression-free survival and response duration were 8.0 and 8.8 months, respectively, and median survival time was 15 months., Conclusions: Triple combination therapy with paclitaxel, S-1, and cisplatin showed promising safety and efficacy profiles with the potential to become a standard regimen for unresectable/metastatic gastric cancer., (Copyright © 2011 S. Karger AG, Basel.)

After distal gastrectomy in a patient with early gastric cancer, 27 regional lymph nodes around the stomach were evaluated for the existence of metastasis. There was a 0IIa+IIc type tumor 2.0 x1.5 cm in size in the gastric angle of the lesser curvature according to the Japanese Classification of Gastric Carcinoma (JCGC). Histologically, the lesion extended no deeper than the muscularis mucosae. The cancer stage was so early that no metastasis was expected to occur but a lymph node with metastasis was found in one lymph node along the common anterior hepatic artery (station No.8a). This histological type was a little different from that of a primary tumor. The doctor began to suspect that the lymph node with metastasis might have been from another patient by mistake. Therefore, DNA typing using the AmpFlSTR Identifiler kit was performed in formaldehyde-fixed paraffin-embedded (FFPE) tissues: 2 parts of gastric mucosa without cancer, one part of gastric mucosa with cancer, 4 lymph nodes without metastasis, and the lymph node station No.8a with metastasis. STR typing was successful in 6~14 STR loci and amelogenin gene, and the detected STR type was the same in all samples. Compared with the STR type using DNA from the patient's blood, the lymph node station No.8a was from the same patient. The lymph node with metastasis turned out to be not from another patient. Therefore, we suggest that DNA typing using the AmpFlSTR Identifiler Kit for FFPE samples is useful in such clinical cases.

Objective: The objective of this study was to determine the dose-limiting toxicity (DLT), the maximum tolerated dose (MTD), the recommended dose (RD) and the preliminary antitumor activity of S-1, oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimide, in combination with cisplatin and paclitaxel for advanced gastric cancer., Patients and Methods: Paclitaxel was administered on day 1. A fixed dose of S-1 (70 mg/m2/day) was orally administered for 14 consecutive days from day 1 and a 24-h infusion of a fixed dose of cisplatin (60 mg/m2) was administered on day 14 of every 28-day cycle. Four dose escalation levels of paclitaxcel were studied (120, 140, 160 and 180 mg/m2)., Results: Twenty patients were enrolled. The toxicities were generally mild no grade 4 hematological toxicity or grade 3 non-hematological toxicity were observed. Level 4 was considered as the MTD because of a treatment delay of more than 2 weeks in 3 out of 6 patients. The RD of paclitaxcel was 160 mg/m2. The overall response rate was 75%., Conclusion: A triple combination chemotherapy consisting of S-1, cisplatin and paclitaxel showed a tolerable level of adverse reactions and favorable antitumor activity.

We have investigated the effect of glycyrrhetic acid (GR) which is metabolic substance of glycyrrhizin, on DNA of human hepatoma (HLE), promyelotic leukemia (HL-60) and stomach cancer (KATO III) cells. GR displayed apoptotic effects against HLE, HL-60 and KATO III cells. The fragmentation of DNA by GR to oligonucleosomal-sized fragments, a characteristic of apoptosis, was dose- and time-dependent in these cell lines. These findings suggest that growth inhibition of these cell lines by GR result from the induction of apoptosis by the compound. Inhibitors of caspases did not suppress the DNA fragmentation caused by GR. N-acetyl-L-cysteine, an antioxidant drug, weakly inhibited the DNA fragmentation caused by GR suggesting that active oxidants work partly as an apoptosis-inducing transfer substance.

Background: The aim of this multicentric trial was to determine the clinical toxicities and antitumor effects of a chemotherapy regimen of S-1 combined with cisplatin in patients with inoperable locally or metastatic advanced gastric cancer., Patients and Methods: Forty-two patients were entered into the study. S-1 (80 mg/m2) was administered orally daily for 14 consecutive days and 24-h infusion of cisplatin (70 mg/m2) was administered on day 8 of every 28-day cycle., Results: The overall response rate was 50% and complete response rate was 5%. The most common adverse event was leucopenia, which occurred with grade 3 in 7 patients (16.6%) and grade 4 in 2 patients (4.8%). Non-hematological adverse events were generally mild. The median survival time was 342 days. The 2-year survival rate was 22.9%., Conclusion: This combination chemotherapy is active, convenient and well tolerated in patients with high-grade advanced gastric cancer.

Background: The efficacy of systemic chemotherapy against peritoneal dissemination from advanced gastric cancer (AGC) remains unclear, because the peritoneal dissemination was not defined as a measurable lesion in conventional phase II studies. In this study, we evaluated the efficacy and toxicity of sequential MTX and 5FU therapy (MF) in chemotherapy-naive patients with AGC accompanied by malignant ascites in a phase II setting., Methods: The treatment schedule comprised weekly administration of MTX (100 mg/m2, i.v. bolus) followed by 5FU (600 mg/m2, i.v. bolus) with a 3 h interval. Leucovorin rescue (10 mg/m2 every 6 h, for a total of six times) was commenced 24 h after MTX administration., Results: Thirty-seven chemotherapy-naive patients with AGC presenting with malignant ascites were enrolled in this trial. The median age was 60 years (range, 25-74 years) and most patients (86%) had a performance status of 0-1. In total, 355 administrations of the sequential MTX/5FU therapy were performed. Major toxicity consisted of myelosuppression and gastrointestinal toxicity. Grade 4 neutropenia occurred in 10.8% of the patients. The overall objective response rate was 5.7% (two partial responses in 35 patients; 95% confidence interval: 0.7-19.2%). However, the response rate of ascites was 35.1% (complete disappearance in three patients and apparent decrease in 10 patients; 95% confidence interval: 20.2-52.5%)., Conclusions: Sequential MTX/5FU therapy is effective against AGC with malignant ascites with acceptable toxicity and warrants further investigations in a phase III setting.

A 51-year-old male patient with esophageal cancer and cervical, thoracic and celiac artery lymph node metastases was treated by combination chemotherapy of TS-1 and cisplatin. TS-1 (80 mg/m2/day) was administered for 14 days followed by 14 days rest as 1 course. Cisplatin (70 mg/m2/day) was administered in 24-hour continuous intravenous infusion at day 8 after the start of TS-1. Before treatment, the tumor marker, CEA showed 27,060 ng/ml. After 5 courses of chemotherapy, endoscopy revealed that the primary tumor had disappeared and no cancer cells were detected by endoscopic biopsy. Chest and abdominal CT scan also showed almost total disappearance of the lymph nodes metastases. CEA decreased to 710 ng/ml. No high-grade toxicities (WHO grade 3 or 4) were seen during the chemotherapy. He is now very well. This TS-1/cisplatin chemotherapy regimen might be a useful treatment for metastatic esophageal cancer.

A 75-year-old male patient with small cell carcinoma of the stomach and liver metastasis was treated by combined chemotherapy of TS-1 and CDDP. One course consisted of TS-1 (120 mg/day) administered for 14 days followed by 14 days rest. CDDP (108 mg/day) was administered by 24-hour continuous intravenous infusion at day 8 after the start of TS-1. After 3 courses, endoscopic examination revealed complete disappearance of the primary tumor with no cancer cells detected by endoscopic biopsy. CT-scan showed that the metastasis of the left lobe of the liver had disappeared and also that the metastasis of the right lobe of the liver was remarkably reduced (75%). The primary lesion was estimated CR, the metastasis PR, and the synthesis PR. The TS-1/CDDP chemotherapy regimen is considered effective for small cell carcinoma of the stomach with liver metastasis.

A 54-year-old patient with scirrhous type 3 gastric cancer having bulky N2 and para-aorta lymph node metastases was treated by combined chemotherapy of TS-1 and CDDP. Before treatment, CEA was 28.4 mg/ml. TS-1 (120 mg/day) administered for 14 days followed by 14 days rest was one course. CDDP (80 mg/m2) was administered by 24 hour continuous intravenous infusion at day 8 after the start of TS-1. After 2 courses of treatment, the level of CEA decreased to 1.4 mg/ml and the primary legion with lymph node metastases had decreased significantly. After 5 courses, endoscopic examination revealed complete disappearance of the primary tumor with no cancer cells detected by endoscopic biopsy. A CT scan also showed complete disappearance of all lymph node metastases. No severe adverse effects (NCI-CTC grade 3 of 4) were observed with this therapy. TS-1/CDDP chemotherapy is considered very effective for scirrhous gastric cancer with far advanced lymph node metastases.

TS-1 is a novel oral fluoropyrimidine anticancer agent and show synergism with CDDP. The objectives of this study were to determine the clinical toxicities, antitumor effect, survival duration, and a recommended dosage schedule in combination with TS-1 and CDDP. Patients with measurable, locally advanced or metastatic gastric cancer were candidates for the study. Three patients were assigned to one of four levels of treatment, as follows. At first, TS-1 was administered orally twice a day for 14 consecutive days followed by 14 days rest and a 24-h infusion of CDDP (70 mg/m2) was administered on day 8 of 28 every 4 weeks. Next, duration of S1 administration was increased in increments of 25% and in increments of 50%. At last, only the dose of CDDP was increased in increments of 10 mg/m2. The first three patients did not have over grade 3 hematologic and nonhematological toxicity during any course. Grade 4 neutropenia occurred during the second course in two patients consecutively in increments of 50% of TS-1. Neutropenia was considered as a dose limiting toxicity. Nonhematologic side effects generally were mild. The overall response rate including all levels was 90.9%. Three complete responses (27.3%) and 8 partial responses (63.6%) were observed among the 11 patients. At first schedule, CR was two of three patients, and PR by the other (overall response rate, 100%). Survival rate of all cases in eight months were 100%. In conclusion, a combination of TS-1 and CDDP chemotherapy showed favorable antitumor activity and less adverse reaction compared to results reported with other chemotherapy. Administration of TS-1 for 14 days followed by 14 days rest, plus CDDP (70 mg/m2) on day 8 every 4 weeks would be recommended in the view of high responsibility and low adverse reaction.

A 79-year-old male was diagnosed as having a scirrhous cancer of the stomach. Carcinomatous peritonitis was suspected on abdominal CT examination and the CA19-9 showed a high level of 95 U/ml. The patient was treated with combined chemotherapy of TS-1 and CDDP. TS-1 (100 mg/day) was administered for 14 days followed by 14 days rest as one course. CDDP was administered in 24-h continuous intravenous infusion on day 8. This treatment was done every 4 weeks regularly. After 5 courses, X-ray and endoscopy examinations revealed disappearance of cancerous lesions in the stomach with an improvement in the extensibility. No cancer cell were confirmed by endoscopic biopsy, nor did a CT-scan detect carcinomatous peritonitis. The CA19-9 decreased within the normal limit. Ten months after chemotherapy was started, the patient was very healthy without a recurrence of cancer. This combined chemotherapy has administered in 8 courses, and during this period no high grade toxicities (WHO grade 3 or 4) occurred. This TS-1/CDDP chemotherapy was effective for scirrhous gastric cancer and might be administered safely even for aged patients.

A 75-year-old male patient was hospitalized for examination of abdominal trouble. Endoscopic examination simultaneously revealed 0-I pl + II c esophageal cancer and type 3 gastric cancer. Endoscopic treatment is impossible to resect the lesion completely. It is difficult for the patient to undergo an operation because he has suffered from a cardiac infarction and pulmonary trouble. Thus, gastric cancer was treated by chemotherapy and esophageal cancer by concurrent chemoradiotherapy with chemotherapy used for gastric cancer. Chemotherapy consisted of CDDP and TS-1 every 4 weeks. TS-1 (100 mg/day) was administered on days 1 to 21, and CDDP (70 mg/m2) was infused for 24 hours on day 8. Radiotherapy (5 days/week) at 2 Gy/day was concurrently started from the beginning of chemotherapy. At day 8 in the 2nd course of chemotherapy, leucocytopenia of grade 2 and appetite loss of grade 3 (NCI-CTC) were seen. Chemoradiotherapy was then suspended for one week. After recovery from toxicity, treatment was continued for a week. A total of 64 Gy was administered. After treatment, endoscopic examination with biopsy revealed the disappearance of gastric and esophageal cancer.

Background: A previous phase II study of doxifluridine in non-elderly patients with advanced gastric cancer demonstrated a favorable survival with mild toxicity, despite a low response rate. The objectives of this study were to evaluate efficacy and feasibility of this agent for elderly patients., Methods: This study protocol required elderly patients, aged 76-80 years, with advanced gastric cancer and having no prior chemotherapy. Doxifluridine, at a dose of 1400 mg/m(2)/day, was administered for four consecutive days followed by a 10-day rest., Results: Between October 1994 and March 1998, 18 patients were registered. The study was then closed because of poor accrual. Toxicity was moderate; three patients suffered from grade 3 anemia and one patient each had grade 3 thrombocytopenia, nausea/vomiting and grade 4 diarrhea. There was one partial response, seven with no change and 10 with progressive disease, yielding a response rate of 5.6%. The median progression-free survival and median survival time for the 18 patients were 55 and 164 days, respectively, with a 1-year survival rate of 5.6%., Conclusions: Although the number of patients was too small to draw any definitive conclusions, this study failed to demonstrate the survival advantage of doxifluridine.

A 67-year-old male patient with gastric cancer of Borrmann type 2 and liver and intra-abdominal lymph node metastases was treated by combined chemotherapy of TS-1 and CDDP TS-1 (100 mg/day) was administered for 14 days followed by 14 days rest as one course. CDDP (70 mg/m2) was administered in 24-hour continuous intravenous infusion at 8 days after the start of TS-1. After 3 courses of treatment, X-ray and endoscopic examinations revealed complete disappearance of the primary tumor and no cancer cells were detected by endoscopic biopsy. A CT-scan also showed complete disappearance of metastatic sites. This combined chemotherapy was finished after 5 courses, and no high grade toxicities (WHO grade 3 or 4), specifically nausea, diarrhea, or leucocytopenia, were seen. This TS-1/CDDP chemotherapy seemed to be effective for advanced gastric cancer in view of toxicities, antitumor effect and QOL of the patient.

A 68-year-old man was diagnosed as having a scirrhous cancer of the stomach. Carcinomatous peritonitis was suspected on abdominal CT examination. Three courses of uracil and tegafur (UFT)/cisplatin (CDDP) chemotherapy were administered. The primary foci were reduced in size, then total gastrectomy was performed. Histological findings revealed a poorly differentiated adenocarcinoma with scirrhous invasion into the subserosa. Histological efficacy of the chemotherapy was judged to be grade 2. The patient has been alive without disease for more than five years after total gastrectomy. Neoadjuvant chemotherapy with UFT and CDDP may have contributed to the favorable clinical outcome in this patient.

We administered a mixture of uracil and tegafur (UFT)/cisplatin (CDDP) chemotherapy in 28 patients with scirrhous gastric cancer. In the regimen, UFT was orally administered at a dose of 200 mg/m2 twice a day. The CDDP was administered at a dose of 90 mg/m2 by 24-hour continuous infusion every 4 weeks. As a result, antitumor effects for primary gastric foci were achieved in 14 of the 28 patients (50%). Ascites from peritoneal dissemination disappeared completely in eight of 13 patients (62%). Total gastrectomy was performed in ten patients after 2 to 3 courses of chemotherapy. Histological response grades assessed on the resected specimen were Grade 2 in four, Grade 1b in three, Grade 1a in one and Grade 0 in two patients. Neoadjuvant chemotherapy is feasible against scirrhous gastric cancer and a subsequent prospective randomized trial should be prepared to clarify the survival benefit of the treatment.

Forty-eight patients with unresectable gastric cancer were enrolled for a randomized trial of FP (n = 24) vs FEP (n = 24) combination chemotherapy with respect to their effects on survival period. Of these, excluding 7 patients, 21 in FP group were treated with 400 mg/m2 UFT po daily and 50 mg/m2 CDDP i.v. on days 1 and 8 every 4 weeks, and 20 in FEP group were treated with 400 mg/m2 UFT po daily, 50 mg/m2 etoposide iv and 50 mg/m2 CDDP i.v. on days 1 and 8 every 4 weeks. In FP group, 10 PR in primary lesions were observed with an overall response rate of 52.4%. In FEP group, 5 PR in primary lesions were observed with an overall response rate of 35.0%. Toxicities over Grade 3 were anorexia (35%), vomiting (25%), and leukopenia (12%), which were manageable. The 50% survival time in FP and FEP group was 233 and 176 days, respectively. Because of the high response rate and prolongation of the survival period, combination chemotherapy with FP seemed to be useful for the treatment of patients with advanced gastric cancer.

A 42-year-old man with a remittent fever was found to have both para-aortic and hepatic tumors with generalized lymphadenopathy. The pathological findings from biopsy specimens from the para-aortic lymph node and hepatic tumor by laparotomy and from left supraclavicular lymphadenectomy showed undifferentiated carcinoma. However, the location of the primary lesion could not be determined. Chemotherapy temporarily reduced the size of the metastatic lymph nodes and the hepatic tumor and also suppressed the remittent fever. Fifteen months after onset, massive polyclonal hypergammapathy developed together with plasmacytosis (30% plasmacytes) in bone marrow, consisting of normal mature plasmacytes. Among cytokines, including interleukin (IL) 1 beta, IL-3, IL-4, IL-6, and tumor necrosis factor alpha, a high value of IL-6 was detected in the serum. Postmortem pathological examination showed the scirrhous type of gastric carcinoma with specific staining by polyclonal antibody against human IL-6. To our knowledge, this is the first report of a gastric carcinoma producing IL-6 associated with fever, hypergammaglobulinemia, and plasmacytosis in bone marrow.

5-fluorouracil analogs investigated in this study include a combination of uracil and Ftorafur (UFT), Ethyl (+/-)-t-butoxy-5-fluoro-hexahydro-2, 4-dioxopyrimidine r-5-carboxylate (TAC-278), and 5'-deoxy-5-fluorouridine (5'-DFUR). In a total of 45 patients with gastric cancer, tumor tissue level of 5-fluorouracil (5-FU) was determined at 2, 4, 6, 8, and 12 hours following the oral administration of drug, using a resected stomach specimen as material. As a result, it was demonstrated that oral administration of 200 mg/m2 of UFT maintained above 0.05 microgram/g (minimum inhibitory concentration: MIC) of 5-FU in tumor tissues over 12 hours in 11 of 13 patients. On the contrary, 133 mg/m2 of TAC-278, and 200 mg/m2 or 300 mg/m2 of 5'-DFUR (which is activated by thymidine phosphorylase in man) did not produce an effective 5-FU concentration in tumor tissues. Serum 5-FU level was high in order of TAC-278, UFT, and 5'-DFUR. Clinical response rates obtained with UFT (200 mg/m2 twice a day), or TAC-278 (133-200 mg/m2, 3 times daily) were 27.5% (49 of 178 cases), and 8.3% (3 of 36 cases, by Koyama et al.), respectively. Fisher's direct probability test revealed that there was a significant difference (p less than 0.05) between them in the response rate. It was considered that the measurement of concentration of anticancer drugs in tumor tissues might provide us useful information for the designing of chemotherapy of gastric cancer.

It became increasingly evident that UFTM chemotherapy, a combination of UFT and mitomycin C is one of the most recommendable therapy for advanced gastric cancer, especially for the treatment of Borrmann type 4 gastric cancer. Objective responses were achieved in 18 out of 26 (69.2%) patients with Borrmann type 4 gastric cancer. Moreover, UFTM-Dpc treatment, a combination therapy of UFTM plus D-penicillamine (suppressor of collagen synthesis), is proposed for the treatment of Borrmann type 4 gastric cancer from the point of view of collagen synthesis inhibition. It is likely that D-penicillamine might inhibit the peritoneal metastatic involvements, which is lethal to the patients finally.

A 69-year-old male visited our hospital in December, 1983, complaining of dysphasia. X-ray and endoscopic examination of the stomach revealed Borrmann's type 3 of the cardia. A biopsy specimen revealed typical features of adenocarcinoma. Because the tumor could not be resected, chemotherapy was started in February, 1984 with a combination of UFT (600 mg/day) and mitomycin (6 mg/week). After five courses of the combination chemotherapy, UFT therapy was continued. Follow-up endoscopy in August, 1985, showed a discolored area of the cardia. A biopsy specimen revealed no evidence of carcinoma. UFT-M therapy is a useful chemotherapy for gastric cancer.