A case of gastric endocrine cell carcinoma with liver metastases treated with S-1/CDDP

Gastric endocrine cell carcinoma is known to be highly malignant with a poor prognosis, and no standard treatment has been established. We experienced a case of gastric endocrine cell carcinoma with liver and lymph node metastases. The lesions became resectable after chemotherapy with S-1/cisplatin (CDDP). The patient was a 68-year-old male. He had gastrointestinal endoscopy for screening without complains. The endoscopy findings showed that a type 3 gastric cancer on lesser curvature of ventricular angle of the stomach, and was histologically diagnosed as an endocrine cell carcinoma by the biopsy specimen. A computed tomography (CT) scan showed metastatic lesions at S2 and S3 of the liver, and No.6 lymph node enlargement. Thus he was diagnosed as gastric endocrine cell carcinoma with liver and lymph node metastases. He was treated chemotherapy with S-1/CDDP every 5 weeks. After these courses of treatment, liver and lymph node metastatic lesions had reduced in size, but the primary lesion was still remained. Then he suffered from a drug induced eruption due to S-1. We changed the chemotherapy to biweekly CPT-11/CDDP. After 21 courses, he underwent distal gastrectomy with lymph node dissection and a partial liver resection. Histological findings revealed that there were no cancer cells in removed specimens. He had treated 8 courses of CPT-11/CDDP therapy after the surgery, and survived for 5 years without recurrence.     

A case of metastatic gastric endocrine cell carcinoma which could be curably resected after chemotherapy with S-1/CDDP

Gastric endocrine cell carcinoma is known to be highly malignant with a poor prognosis, and no standard treatment has been established. We experienced a case of endocrine cell carcinoma of the stomach with liver and lymph node metastases. The lesions became resectable at curability B after chemotherapy with S-1/cisplatin (CDDP). A 59-year-old man, who had no specific complaint, had gastrointestinal endoscopy for screening. A 30-mm tumor was found at the greater curvature of the lower body of the stomach, and was histologically diagnosed as an endocrine cell carcinoma from the biopsy specimen. A computed tomography (CT) scan and abdominal magnetic resonance imaging (MRI) showed masses at S5 and S6 of the liver, and No. 4 lymph node enlargement. Diagnosed as gastric endocrine cell carcinoma with liver and lymph node metastases, he was referred to our hospital. We started chemotherapy with a daily dose of S-1 administered on days 1 to 14 and CDDP of 70 mg/m(2) on day 8, every 4 weeks. After three courses of treatment, the primary lesion became a small scar and the metastatic lesions vanished from the CT and MRI. Then we performed distal gastrectomy with lymph node dissection and partial liver resectomy. Histological findings revealed no cancer cells, except for a few cells in the S5 liver lesion.     

Two cases of gastric endocrine cell carcinoma

Gastric endocrine cell carcinoma is rare and associated with a poor prognosis. The first case was a man in his sixties with gastric endocrine cell carcinoma, of which a clinical finding was T2N1M0H1 (Stage IV). S-1 + CDDP therapy was selected and failed. CDDP+CPT-11 therapy was started and CT showed a partial response in ten months. But the tumor was re-grown and the patient died twenty months after diagnosis. The second case was a man in his seventies with gastric endocrine cell carcinoma, of which a clinical finding was T3N1M0H0P0, Stage IIIa, underwent total gastrectomy. Abdominal contrast-enhanced CT scan performed a month after the operation disclosed hepatic metastasis. After two months of S-1 regimen, CDDP + CPT-11 therapy was started.     

A case report of bowel obstruction due to peritonitis carcinomatosa using combined administration with CPT-11 and CDDP

We report here a case of recurrent gastric cancer that responded to third-line chemotherapy with CPT-11 and CDDP. The patient was a 61-year-old man with recurrent gastric cancer, who had administered TS-1 for first-line chemotherapy and paclitaxel for second-line chemotherapy. After such therapy, bowel obstruction was revealed due to peritoneal dissemination. The patient underwent third-line chemotherapy with CPT-11 and CDDP after drainage of gastrointestinal juice by nasogastric tube. The treatment schedule for CPT-11 and CDDP therapy consisted of CPT-11 60 mg/m2 div at day 1, day 15 and CDDP 60 mg/m2 div at day 1. It was repeated every 4 weeks. After first administration, the bowel obstruction was improved, so the treatment was continued for 8 months on an outpatient basis. These findings imply that this treatment can be a useful second-line or third-line chemotherapy for unresectable advanced or recurrent gastric cancer.     

A case of recurrent pleural effusion and positive cytology of advanced gastric cancer treated by TS-1 plus weekly taxane as second-line chemotherapy

A second-line chemotherapy for advanced gastric cancer has not been established. We report a case of good response in a 39-year-old woman who had recurrent pleural effusion and positive cytology of type 4 gastric cancer and was treated with TS-1, a DPD inhibitory fluoropyrimidine, in combination with weekly taxane. After a partial response for type 4 gastric cancer from the treatment with 2 courses of TS-1 plus low-dose cisplatinum (CDDP), followed by outpatient chemotherapy with TS-1 alone or TS-1 plus weekly CDDP, left pleural effusion appeared and CA19-9 increased during the 7th course of the chemotherapy. Cytology of the effusion was class IV. The patient was treated with a course of TS-1 (120 mg/day, day 1-21) plus paclitaxel (50 mg/m2, day 1, 8) followed by 2 week washout. In the following courses, paclitaxel was replaced with docetaxel (30 mg/m2, day 1 and 8) and the course was continued in the outpatient setting. After 2 courses, the left pleural effusion disappeared and remained absent after 6 courses. Gastric biopsy showed no cancer cells and abdominal CT showed no recurrence. Serum CA19-9 doubled 1 week after taxane treatment and decreased gradually week by week during the course. This case suggests that a combination of TS-1 and taxane is effective against recurrent pleural effusion of advanced gastric cancer and useful as a second-line chemotherapy.     

A case of gastric cancer with abdominal para-aortic lymph node metastases responding to TS-1 + CDDP neoadjuvant chemotherapy

The patient was a 54-year-old woman with extremely advanced gastric cancer of type 3. A CT scan of the abdomen showed enlargement of many huge abdominal para-aortic lymph nodes. Combined chemotherapy of TS-1 and CDDP was planned in order to reduce the tumor. TS-1 (100 mg/body/day) was administered for 21 days followed by 14 days rest as one course. CDDP (96 mg/body) was administered 8 days after the start of TS-1. After 2 courses of treatment, a CT scan showed complete disappearance of lymph node metastasis, and no high grade toxicities. Therefore, one month after the completion of the chemotherapy, total gastrectomy and D2 lymph node dissection were performed. The histological effect was judged to be grade 1a-1b. There were no viable cancer cells in any lymph nodes. One year after surgery, the patient is still alive without recurrence. Neoadjuvant chemotherapy with TS-1 and CDDP is so effective that can it be adapted for advanced gastric cancer with para-aortic lymph node enlargement for downstaging.     

A case treated successfully with low-dose CDDP and 5-FU for the treatment of liver and para-aortic lymph node metastases and second metastasis to anterior mediastinum lymph nodes from gastric cancer after gastrectomy

A 64-year-old-male had recurrent paraaortic lymph node and liver metastases eight months after total gastrectomy and with distal pancreatectomy and splenectomy for advanced gastric cancer. Combined chemotherapy with 5-FU and a low-dose of CDDP was effective and the both lesions disappeared. Thirteen months later, a second recurrence of anterior mediastinum lymph node metastases occurred. After the same protocol, the lesions showed a partial response and lymph node dissection was performed. Histopathological examination showed that the resected lymph nodes had 99% necrosis and fibrotic change. Immunohistochemical examination of p53 of the primary gastric cancer showed negative staining. The patient has been followed for three years after the operation, and has no recurrent lesions.     

Complete response in an elderly patient with advanced gastric scirrhous cancer treated with combined chemotherapy of TS-1 and CDDP

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 successful resected case of advanced esophageal cancer with early gastric cancer responding to neoadjuvant chemotherapy of docetaxel, CDDP and 5-FU

A 72-year-old male with a chief complaint of dysphagia was admitted to our hospital. Upper gastrointestinal endoscopic examination showed double cancers with thoracic esophageal cancer in the middle esophagus and gastric cancer in the antrum. Pathological examinations of the double cancer revealed the first one to be moderately-differentiated squamous cell carcinoma and the second to be well-differentiated adenocarcinoma. Computed tomography (CT) of the chest and abdomen showed no distant or lymph node metastases. Clinical stagings of the double cancer were stage II (T2N0M0)in esophageal cancer and stage I A (T1N0M0) in gastric cancer. The patient received neoadjuvant chemotherapy using docetaxel, CDDP and 5-FU. After 2 courses of chemotherapy, the adverse event was grade 2 in leucopenia and grade 2 in alopecia. Repeated macroscopic and histological examinations after chemotherapy revealed that the esophageal cancer had significant reductions in the size of tumors, leading to a partial response, and the gastric cancer had disappeared, leading to a complete response. He underwent thoracoscopy-assisted esophagectomy in the prone position, and laparoscopy-assisted gastric tube reconstruction. This neoadjuvant chemotherapy of docetaxel, CDDP and 5-FU might be effective and tolerable as with patients with double cancer of esophageal and gastric cancers.     

A partial response to combined TS-1 and docetaxel chemotherapy enabling a curative resection after the failure of combined TS-1 and CDDP chemotherapy in a patient with unresectable gastric cancer

A 60-year-old man visited our hospital complaining of epigastric pain. Gastrofiberscopy revealed an advanced gastric cancer located on the anterior wall of the antrum. Abdominal computed tomography (CT) revealed metastases to the paraaortic lymph nodes. The patient subsequently underwent combined chemotherapy consisting of TS-1 and low-dose CDDP for the treatment of unresectable gastric cancer. No reductions in the paraaortic lymph node metastases were noted after one cycle. The patient was then treated with TS-1 combined with docetaxel as a second-line chemotherapy. TS-1 (80 mg/m2) was orally administered for 2 weeks followed by a 2 week interval, while docetaxel (25 mg/m2) was simultaneously administered weekly (days 1, 8, and 15). One cycle of chemotherapy was 28 days. An abdominal CT revealed a partial response after 3 cycles. The patient experienced grade 2 leukocytopenia and grade 3 neutropenia. We decided that the patient could undergo a curative resection, and a distal gastrectomy with D2+para-aortic LN dissection was performed. The pathological efficacy was Grade 2. The patient is presently alive with no sign of recurrence after 20 months. Combined TS-1 and docetaxel chemotherapy is a promising second-line regimen for the treatment of unresectable gastric cancer, after treatment with TS 1 combined with CDDP has failed.     

Three successful cases with CPT-11 + CDDP chemotherapy where S-1 failed to respond to recurrent gastric cancer

We report three successful cases with irinotecan (CPT-11 60 mg/m2) + cisplatin (CDDP 30mg/m2) chemotherapy (once in 2 weeks) where S-1 failed to respond to recurrent gastric cancer. Case 1: A total gastrectomy and splenectomy were performed for a cardiac gastric cancer (T3, N2, H0, P0, CY0, por 1, Stage IIIB). An abdominal CT revealed paraortic lymph node metastases 4 months after the surgery. No reductions were noted after S-1 monotherapy. We next treated this patient with CPT-11 + CDDP. An abdominal CT revealed a CRin after 11 courses. Case 2: A total gastrectomy, splenectomy and cholecystectomy were performed for a cardiac gastric cancer (T3, N3, H0, P0, CY1, tub1, Stage IV). After the surgery, we treated this patient with S-1 mono-therapy. However, we finished this treatment for abdominal recurrence. We next treated this patient with CPT-11 + CDDP. An abdominal CT revealed a CR after 24 courses. Case 3: A distal gastrectomy and cholecystectomy were performed for a pyloric gastric cancer (T2, N1, H0, P0, CY0, tub 2, Stage II). An abdominal CT revealed paraortic lymph node metastases 10 months after the surgery. We treated this patient with S-1 + paclitaxel (PTX) chemotherapy. No reductions were noted after 2 courses. We next treated this patient with CPT-11 + CDDP. An abdominal CT revealed a CR after 8 courses.     

Two cases of recurrent gastric cancer treated by combined chemotherapy of TS-1 and low-dose cis-platinum

We report 2 patients with recurrent gastric cancer treated by combined chemotherapy of TS-1 and low-dose cis-platinum (TS-1/LCDDP). Who both obtained long-term survival while maintaining good QOL. Case 1: A 60-year-old man underwent total gastrectomy for gastric cancer (pT3, pN2, Stage III B). Three months after surgery, multiple liver metastases were identified, for which TS-1/LCDDP therapy (TS-1 100 mg/body/day, CDDP 10 mg/body/week; 1 course for 4 weeks) was started without hospitalization. After CR was obtained after 4 courses, an additional 4 courses were carried out. At present, 1 year and 11 months have passed since the initial treatment, and CR has been maintained. Regarding adverse events, only grade-1 pigmentation was observed. Case 2: A 65-year-old man with gastric cancer (pT3, pN1, Stage III A) underwent distal gastrectomy. One year after surgery, CT showed both multiple liver and pulmonary metastases. Twelve courses of TS-1/LCDDP therapy have been carried out for 2 years and 4 months. Therapeutic effect was NC, but the patient was able to tolerate the treatments as an outpatient without any subjective symptoms. Leukopenia (grade 2), pigmentation, stomatitis and nausea (grade 1) were observed. Both patients received TS-1/LCDDP therapy as outpatients with good QOL and performance status (0). Recently, chemotherapy for recurrent cancer has been focusing on long-term survival and maintenance of QOL, instead of tumor shrinkage. These results suggest that TS-1/LCDDP treatment is useful as a first-line chemotherapy for patients with recurrent gastric cancer.     

A case of type 4 gastric cancer,diagnosed after operation for Krukenberg's tumor,treated by TS-1 plus low-dose cisplatinum

Survival of patients with advanced gastric cancer with Krukenberg's tumor is poor. We report the case of a good response in a 37-year-old woman who had type 4 gastric cancer, diagnosed after the operation of Krukenberg's tumor, and then was treated with TS-1, a DPD inhibitory fluoropyrimidine, in combination with a low-dose cisplatinum (CDDP). Endoscopic gastric biopsy showed signet-ring cell adenocarcinoma and moderately differentiated tubular adenocarcinoma, and computed tomography (CT) showed the para-aortic lymph node metastasis before the chemotherapy. The patient was treated with two courses of TS-1 (100 mg/day, day 1-21) plus CDDP (10 mg/m2, day 1-5, 8-12, 15-19) with two-week interval. After the first course, gastric biopsy did not show any cancer cells and lymph node metastasis had disappeared. Serum CA19-9 decreased gradually week by week during the chemotherapy, even during the washout period after the first course, and was normalized after two courses. This case suggests that the combination of TS-1 and low-dose CDDP is effective against type 4 advanced gastric cancer.     

A case of multiple skin metastases from gastric cancer successfully treated with docetaxel combined with doxifluridine

The results of treatment of gastric cancer with docetaxel have scarcely been reported. Combination chemotherapy of docetaxel and doxifluridine was administered to five patients with recurrent or unresectable gastric cancer in the authors' department, and the overall response rate was 40%. Among them, we report here a case of multiple skin metastases successfully treated with this chemotherapy. A 71-year-old man had already undergone total gastrectomy with splenectomy about one year previously because of advanced gastric cancer: type 3, tub2, se, n1, INF gamma, ly3(+), v1(+), stage IIIa. He was treated with adjuvant chemotherapy of low-dose FP (CDDP/5-FU) for two weeks, and thereafter 5-FU (200 mg/day orally) was administered. Skin metastases appeared on the right upper eyelid and the left femoral region, though no recurrent findings were detected by CT, US, and the like one year after operation. The combination chemotherapy of docetaxel and doxifluridine was administered because multiple skin tumors rapidly appeared on the back and the right upper eyelid region. These tumors disappeared after 3 weeks and he has had no recurrence more than one year after chemotherapy.     

A case of advanced gastric cancer successfully treated by TS-1 and CDDP after jejunostomy

A 65-year-old female with unresectable advanced gastric cancer accompanied by multiple lung metastases underwent jejunostomy and was treated with TS-1 and CDDP. One course consisted of TS-1 (80 mg/day) via an intestinal fistula tube from days 1 to 14 followed by 14 days rest and CDDP (80 mg/day) was administered by 24-hour continuous intravenous infusion on day 8. After 3 courses, the primary tumor and lymph node metastases decreased in size (PR), and CT scan showed the multiple lung metastases had disappeared. Total gastrectomy (D 2) and splenectomy were performed after chemotherapy. The final diagnosis was Stage IIIA and the pathological response to chemotherapy was Grade 2. The patient has survived for over 14 months after surgery and has presented no signs of recurrence.     

A case of gastric cancer with paraaortic lymph node metastasis responding to TS-1/CDDP as neoadjuvant chemotherapy

A 64-year-old male visited our hospital with complaints of epigastric pain. Computed tomography (CT) showed gastric cancer with extensive paraaortic lymph node metastasis. We decided that a curative operation was impossible, and administered the following chemotherapy. After 120 mg/day of TS-1 was orally administered for 3 weeks followed by 2 drug-free weeks with 90 mg of CDDP was administered intravenously on day 8, CT showed a 90.6% reduction in the paraaortic lymph node metastasis. No serious adverse reaction was observed. After 2 courses of this chemotherapy, surgery was performed after informed consent was obtained from the patient. Histrogical result showed PR. The patient is now healthy and no sign of recurrence has been observed. TS-1/CDDP therapy is useful for advanced gastric cancer.     

Trans-arterial infusion chemotherapy through the inferior epigastric artery for malignant abdominal tumors without laparotomy

A new technique of intra-arterial catheterization through the inferior epigastric artery using a subcutaneously-implanted silicon reservoir was tried for arterial infusion chemotherapy in patients with cancer located in specific lesions. Eight surgically uncontrollable tumors, consisting of 6 hepatic metastasis, one surgically incurable gastric cancer and one recurrent rectal cancer, were treated by continuous arterial infusion of cis-diamminedichloroplatinum (CDDP) using this new method. Clinical antitumor effect was evaluated by CT scan, sonography or operation. CR, PR and NC were observed in 3, 3 and 2 patients, respectively. No significant difference in CDDP levels in serum was found between CR plus PR and NC cases. Since this method can be done without laparotomy, more patients may benefits from arterial infusion chemotherapy.     

Three successful case reports of advanced gastric cancer with chemotherapy

We report three successful cases with continuous systemic chemotherapy for advanced gastric cancer. Case 1: A 67-year-old male with gastric cancer. Abdominal CT showed the invasion in the pancreas and as a result, continuous systemic infusion of low-dose cisplatin (CDDP 20 mg/day) and 5-fluorouracil (5-FU 1,000 mg/day) was performed. This infusion chemotherapy, CDDP and 5-FU, was continued for 5 days and discontinued for 25 days. Three months after the chemotherapy, the main tumor was remarkably reduced (downstaging was obtained), and consequently, total gastrectomy was performed. Case 2: A 78-year-old male with gastric cancer and hepatic multiple metastases. Abdominal CT scan before operation did not reveal the hepatic metastasis. In the operation for distal gastrectomy, we found multiple metastases on the surface of the liver. Continuous systemic infusion of low-dose CDDP (20 mg/day) and 5-FU (1,000 mg/day) was performed. This infusion chemotherapy, CDDP and 5-FU, was continued for 5 days and discontinued for 2 days. One month after the chemotherapy, Liver metastases had almost disappeared. Case 3: A 73-year-old male had received a distal gastrectomy based on the diagnosis of gastric cancer. The tumor marker, CA19-9, immediately decreased after the operation, but had increased again. He was treated with a combination chemotherapy of TS-1 and CDDP. The treatment consisted of 4 weeks of TS-1 administration (100 mg daily) followed by a 2-week break. CDDP of 10 mg/day was infused intravenously (day 1-5). Four weeks after the infusion, CA19-9 had returned to almost normal. We conclude that the combination chemotherapy of 5-FU (or TS-1) and CDDP might be an effective treatment for advanced and metastatic gastric cancer.     

Three cases of advanced gastric cancer treated by TS-1 in combination with low-dose cisplatinum

TS-1, a DPD inhibitory fluoropyrimidine, is a novel oral formation of 5-fluorouracil (5-FU). In patients with advanced gastric cancer, the response rate was reportedly over 40%. We report three cases of advanced gastric cancer treated using TS-1 in combination with a low-dose of cisplatinum (CDDP) that well responded. Case 1: A 62-year-old women underwent total gastrectomy. Ten weeks later, she suffered intestinal obstruction due to peritoneal recurrence of gastric cancer. Eighty mg of TS-1 in combination with bi-weekly administration of CDDP (10 mg) improved her intestinal obstruction. Case 2: A 50-year-old man suffered peritoneal recurrence of gastric cancer. Computed tomography (CT) showed intestinal obstruction, ascites, and hydronephrosis. After 100 mg of TS-1 in combination with bi-weekly administration of CDDP (20 mg) for 1 year, CT showed almost complete improvement of peritonitis carcinomatosa. Case 3: A 58-year-old man, who suffered advanced gastric cancer with peritonitis carcinomatosa, was administrated 100 mg of TS-1 in combination with bi-weekly administration of CDDP (20 mg). After 2 months of administration, remarkable improvement was observed in the upper gastrointestinal series. Adverse reactions, which were grade 1 for stomatitis, were observed only in case 1. All three patients are alive (case 1 and 2 have survived more than one year) and therapy is continuing. In conclusion, combined chemotherapy of TS-1 and low-dose CDDP was effective and well tolerable for advanced gastric cancer patients. It was suggested that effective biochemical modulation might be achieved by these two drugs.     

Two resected cases of advanced gastric cancer with peritoneal dissemination after successful treatment with TS-1 plus low-dose CDDP

We report two resected cases of advanced gastric cancer with peritoneal dissemination after successful treatment with TS-1 plus low-dose CDDP. Patient 1 presented with right hypochondralgia and underwent laparotomy with diagnosis of type 4 gastric cancer by gastrointestinal fiberscopy. However, the tumor was judged to be unresectable due to peritoneal dissemination, and chemotherapy was performed. At the completion of course 1, he underwent laparotomy again. Although the tumor involved the body of the pancreas and transverse colon, there was no peritoneal dissemination. Therefore, a total gastrectomy was performed with distal pancreatectomy, partial colectomy, cholecystectomy, and D2 lymph node dissection. Patient 2 presented with anorexia and was diagnosed with type 3 gastric cancer by gastrointestinal fiberscopy. CT revealed the tumor was unresectable due to peritoneal dissemination, and so chemotherapy was performed. He underwent laparotomy at the completion of course 3. There was no peritoneal dissemination, so a total gastrectomy was performed with cholecystectomy and D2 lymph node dissection. Both patients remain alive and in good condition without any signs of recurrence after surgery.