[Strategy of treatment for gastric cancer with peritoneal metastasis].

In advanced gastric cancer with peritoneal metastasis, adjuvant chemotherapy after primary tumor resection showed considerably poor prognosis with a median survival time of only 232 days. So, we changed the strategy that we start systemic chemotherapy at the earliest opportunity without resecting the primary tumor for gastric cancer patients who were diagnosed peritoneal metastasis by laparotomy or staging laparoscopy. Eleven cases of gastric cancer with peritoneal metastasis were administered systemic chemotherapy first including S-1+paclitaxel (PTX). The regimen of chemotherapy of two weeks administration of S-1 (80 mg/m2/day)followed by one week rest and injections of PTX (50mg/m2) at day 1 and 8 for 21 days as one course. Five of eleven cases were performed S-1+PTX as the first-line, the other six cases as the second-line. In some cases, this therapy led to transient responses. Ultimately, most of them showed progressive disease. However, two of eleven cases showed a complete response in the peritoneal metastasis and could receive radical operation for gastric cancer. Both patients were still alive without any relapse at the time of this report. The median survival time of eleven cases of gastric cancer with peritoneal metastasis performed the systemic chemotherapy first with this regimen was 464 days. The survival was considerably prolonged (p=0. 0500), compared to 232 days in postoperative cases.

[Therapeutic outcome and prognosis in S-1+CDDP chemotherapy for advanced gastric cancer--postoperative histopathological assessment].

UNLABELLED: The efficacy and prognosis with neoadjuvant chemotherapy(NAC)for advanced gastric cancer were assessed by histopathological examination of resected tumors. The subjects consisted of cases (< or =75 y.o.) having type 4/large type 3 (diameter> or = 8 cm) gastric cancer curable by resection based on preoperative imaging diagnostics. The NAC regimen consisted of oral S-1 at 80-120 mg/body on Days 1-21 and CDDP at 60 mg/m2 on Day 8. After two courses, gastrectomy with D2 or more extended lymph node dissection was performed. Based on histopathological effect grading of resected tumors, patients were classified into responder(grade 2 or above)or nonresponder(grade 1b or below)and analyzed for TS and OPRT gene expressions and prognosis. There were 5 responders and 6 nonresponders. High OPRT expression was mainly associated with responders. On the other hand, high TS expression with low OPRT expression was more frequently associated with nonresponders. At a median follow-up of more than 56 months (minimum follow-up, 54 months; maximum follow-up, 60 months), the 4-year overall survival was 36. 4%. Compared to nonresponders, responders showed a longer survival (p=0. 0864) and relapse-free period (p=0. 0414). CONCLUSION: These results suggest that NAC with S-1+CDDP is promising against resectable advanced gastric cancer; however, its true value will only emerge after completion of the ongoing phase III study of NAC plus surgery and postoperative chemotherapy for resectable large type 3/type 4 advanced gastric cancer (JCOG0501).

[A multi-centric phase I/II study of intraperitoneal docetaxel combined with S-1 for patients with peritoneal dissemination of gastric cancer].

To determine the safety profile and activity of IP docetaxel combined with S-1 for patients with peritoneal dissemination of gastric cancer, a multi-centric phase I/II study has started. Patients with histologically confirmed peritoneal dissemination by laparoscopy or laparotomy were eligible to participate in this study, but the patients with a large amount of malignant ascites were excluded. In phase I part, the patients received variable doses of intraperitoneal docetaxel on day 1 and day 15 and 80 mg/m2 of daily oral S-1 on days 1-14 every 4 weeks. Phase I part determines the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD) and recommended dose (RD), and phase II part evaluates a safe successful execution. The response rate of peritoneal dissemination was explored as the secondary endpoint. After 2 cycles, peritoneal tumor response was assessed according to the new criteria of Society for the Study of Peritoneal Dissemination in Gastric Cancer. The response criteria included the following: a decrease in ascites and change in cytology negative; at least a 50% decrease in the sum of the longest diameter of peritoneal tumor using photographs of peritoneal lesions taken to confirm an objective response before and after the treatment.

[Neoadjuvant chemotherapy using TS-1 and CDDP against large type 3/Type 4/Bulky N 2 advanced gastric cancer].

This study was conducted to assess therapeutic results following neoadjuvant chemotherapy (NAC) for large type 3/type 4/Bulky N 2 advanced gastric cancer having a poor prognosis following resection. The subjects consisted of cases (< or = 75 y.o.) having large type 3 (diameter > or = 8 cm), type 4 or Bulky N 2 gastric cancer curable by resection based on preoperative imaging diagnostics. The NAC regimen consisted of TS-1 at 80-120 mg/body on days 1-21 p. o. and CDDP at 60 mg/m2 on day 8 divided. Upon completion of two courses of 4 weeks per course, gastrectomy with > or = D2 lymph node dissection was carried out on days 21-34. The average age of the subjects was 60.7 years, and the therapy completion rate was 80% (8/10 cases). Five of ten cases were responders diagnosed as grade 2 by histopathological examination of excised specimens (response rate 50%). Two of five responders were histopathologically evaluated as down-staging as a result of NAC (Stage III A--> f Stage I A, Stage IV--> f Stage I A). Three of the five non-responders have relapsed, and the relapse-free interval was an average 238 days. In the five responders,one has relapsed at 331 days,while the other 4 responders have shown no relapse yet. Although NAC consisting of TS-1 and CDDP is considered to be effective against advanced gastric cancer, a phase III study with surgical treatment only will be necessary to confirm its true value.

[A phase I study of combination chemotherapy using TS-1 and pirarubicin (THP) for advanced gastric cancer].

The safety of chemotherapy combining TS-1 and pirarubicin (THP) for treatment of recurrent or locally advanced gastric cancer was evaluated. THP was administered by intravenous drip infusion at a dose of 14 mg/m2 every other week. TS-1 was administered orally at a dose of 40 mg/m2 twice a day for 2 weeks followed by 2 weeks of rest (level 1), for 3 weeks followed by 2 weeks of rest (level 2), and for 4 weeks followed by 2 weeks of rest (level 3). Three patients were treated with the level 1 schedule. One patient with peritoneal dissemination received 22 courses of the treatment, and benefited from a long-term NC. However the remaining 2 cases were diagnosed as PD after 4 courses and were withdrawn from further treatment. Two patients in this group suffered from grade 2 adverse events according to the NCI-CTC. Only 1 patient who had liver metastasis was treated at level 2. Fourteen courses were administered, and a PR was achieved while grade 2 adverse events were observed. One of 3 patients who were treated with level 3 had grade 3 adverse events. Consequently, 3 more cases were added to this dose level, and no additional grade 3 adverse events were observed, while grade 2 adverse events were seen in 4 cases. Urinary urgency had completely disappeared in 1 patient with peritoneal recurrence. Myelosuppression, which was the main observed adverse event, was well controlled and of brief duration. The response, including alleviation of clinical symptoms, was confirmed in 3 of 5 chemo-naive patients.

Malignant lymphoma occurring in the residual stomach following gastrectomy: plus discussion based on the literature in Japan.

Malignant lymphoma of the remnant stomach was diagnosed in a 53-year-old man 8 years after gastrectomy for a perforated gastric ulcer. Endoscopic examination demonstrated protruding lesions spreading over the entire residual stomach, and biopsy revealed malignant lymphoma. Rectal cancer was diagnosed simultaneously. The residual stomach was completely excised, with splenectomy, in parallel with low anterior resection of the rectum. Histological studies revealed that the lesion in the residual stomach was a lymphoma of the diffuse, large-cell type, according to the Lymphoma-Leukemia Study Group (LSG) classification, with positivity for CD20 and CD45RA, leading to a diagnosis of B-cell lymphoma. Helicobacter pylori microorganisms were found on the luminal surface of the tumor. Despite postoperative chemotherapy, the patient died of disseminated lymphoma 34 months later. Although malignant lymphoma occurring in the residual stomach following gastrectomy is rare, particular attention should be given to the possible presence of a malignant tumor when examining the residual stomach following gastrectomy.

Differential alternative splicing expressions of thymidylate synthase isoforms.

We identified two novel deletion variants of the thymidylate synthase transcript in gastric cell lines. Sequence analyses indicate that none of these variants results in introduction of a premature stop-codon or a frame shifts. In 39 gastric cancer samples, both the full-length and one-deletion variant messages were detected in cancerous as well as non-cancerous tissues. However, another isoform was found in only seven of 39 cancerous tissues. Our results provide important information to assist more detailed studies on the regulation of thymidylate synthase activity.

A patient with small-cell carcinoma of the stomach with long survival after percutaneous microwave coagulating therapy (PMCT) for liver metastasis.

A 66-year-old man was admitted to our hospital with epigastralgia. Preoperative examinations revealed an 8.0 x 8.0-cm, Borrmann type 2 tumor in the posterior wall of the cardia, without distant metastases. Total gastrectomy with pancreato-splenectomy and regional lymph node dissection was performed curatively. Histologically, the tumor was composed mainly of small cells with hyperchromatic nuclei and scant cytoplasm, which showed positive staining for Grimelius, gamma-neuron-specific enolase (gamma-NSE), chromogranin A, and serotonin. About 10 months after the operation, a solitary tumor was revealed in S8 of the liver by abdominal computed tomography (CT), and it was histologically confirmed by needle biopsy to be a metastasis of the small-cell carcinoma from the stomach. Instead of hepatectomy, percutaneous microwave coagulating therapy (PMCT) was indicated, because of the patients' liver dysfunction (ICG R15, 39.9%); CT showed complete necrosis of the metastatic focus in the liver after the PMCT. Now, 33 months after the first detection of the liver metastasis (43 months after the gastrectomy), the patient is still alive without any growth of the liver metastasis. The 67 previously reported cases of small-cell carcinoma of the stomach in Japan, including ours, are also reviewed.