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.     

A case of gastric neuroendocrine cell carcinoma successfully treated by neoadjuvant chemotherapy

A 74-year-old man, whose chief complaint was epigastralgia, was referred to our hospital and diagnosed gastric cancer with liver metastasis. Gastrointestinal endoscopy showed a tumor on the lesser curvature of cardia of stomach. He was diagnosed as neuroendocrine cell carcinoma by biopsy specimens. He was treated by combined chemotherapy of CPT-11 and CDDP. After 11 courses, endoscopic examination revealed a complete disappearance of the primary tumor. CT-scan and MRI showed that the liver metastasis had been disappeared. We diagnosed as clinical CR and performed total gastrectomy with lymph node dissection and partial hepatectomy. Histological findings revealed a few cells in stomach and no cancer cells in the liver. He was treated with adjuvant chemotherapy of S-1. After 3-course, he suffered from anemia of grade 3, thus we interrupted chemotherapy. The patient remains alive for 28 months without recurrence. We conclude that chemotherapy was effective for neuroendocrine cell carcinoma of the stomach, which was to be considered of poor prognosis, and that liver resectomy was often effective.     

A case of esophageal small cell carcinoma with multiple liver metastases responding to chemotherapy with irinotecan plus cisplatin

We report a case of small cell esophageal carcinoma (SCEC) with multiple liver metastases treated with some success by chemotherapy with irinotecan (CPT-11) plus cisplatin (CDDP). Radiologic and endoscopic examination of a 75-year-old man with multiple liver tumors disclosed a 4.0-cm type 2 tumor in the middle third of the esophagus. An endoscopically obtained biopsy specimen was diagnosed as undifferentiated small cell carcinoma. Multiple liver metastases were confirmed but lymph node metastases and distant metastases other than those in the liver were not detected. After six courses of chemotherapy with CPT-11 plus CDDP, the primary lesion showed complete response and liver metastases showed partial response. However, because all lesions almost immediately relapsed or progressed, arterial infusion chemotherapy for liver metastases and radiation for the primary lesion were given as second-line treatment. The primary lesion showed complete response with radiation. Arterial infusion chemotherapy prevented the progression of liver metastases once, but the patient died of liver failure at last. No distant lesions including metastatic lymph nodes were confirmed over the course of his illness, and the patient survived for a year after first diagnosis. Although the prognosis of SCEC is quite unfavorable due to highly aggressive behavior, a better prognosis is possible with effective chemotherapy and second-line treatment is important in improving prognosis.     

A case report of small cell carcinoma of the esophagus successfully treated by irinotecan and cisplatin

Small cell carcinoma of the esophagus is regarded as having a poor prognosis with frequent and early recurrence against various treatments. We have experienced a case of small cell carcinoma of the esophagus manifested by massive lymph node metastasis in the upper mediastinum successfully treated by CPT-11 and CDDP, and that a patient survived for 17 months after the initial treatment. A 62-year-old man underwent endoscopy due to a disturbance of the food passage. Pathological evaluation of biopsy specimen revealed small cell carcinoma of the esophagus. As he was diagnosed with bilateral lymph node metastasis in the upper mediastinum by CT scan, a systemic chemotherapy with CPT-11 and CDDP was adopted. After 2 courses of chemotherapy he could be discharged as the size of the tumor was reduced. After 3 courses of additional chemotherapy 8 months after the initial treatment, a recurrent tumor was indicated at the right side of the lymph node of the neck. A weekly radiation with concurrent administration of docetaxel was carried out as a second line treatment. He is surviving for 17 months after the initial treatment without any evidence of recurrence. Due to histo-pathological similarity, a treatment for small cell carcinoma of the esophagus resembles that of the lung. Recently, the combined treatment of CPT-11 and CDDP was reported to demonstrate a better influence on a patient's survival for small cell carcinoma of the lung. For the esophagus, CPT-11 and CDDP was also an effective treatment.     

A resected case of advanced gastric cancer with multiple liver metastasis successfully treated by preoperative and postoperative S-1/CPT-11 combination chemotherapy

CASE: A 75-year-old man was admitted for anemia, and a tar stool found by endoscopic examination revealed a type 3 advanced gastric cancer in the lower stomach. Multiple liver metastases 4 cm in diameter were shown on CT. Because we thought that the case was unresectable, S-1/CPT-11 chemotherapy was performed. S-1 (80mg/body/day) was orally administered for 2 weeks followed by a drug-free 1 week, and CPT-11 (100mg/body/day) was given intravenously on days 1 and 8. After 3 courses of chemotherapy, the primary lesion, the regional lymph nodes, and the metastatic lesion of the liver were slightly reduced in size. He was judged as clinical PR, and distal gastrectomy and lymph node dissection were performed. One month after surgery the tumor marker values became normal, and CT could hardly detect metastatic liver tumors. Now, after 3 years, the PR stage has been maintained. Combined use of peroral S-1 and CPT-11 by intravenous infusion is effective for multiple liver metastasis after gastrectomy in gastric cancer.     

Successful combination chemotherapy for a case of small cell carcinoma of the rectum with multiple liver metastasis

A 69-year-old-man with small cell carcinoma of the rectum and multiple liver metastases was admitted in December 1996. Poorly differentiated adenocarcinoma was preoperatively diagnosed in a biopsy specimen from the rectum. Chemolipiodolization using 50 mg DXR and 6 ml lipiodol was performed for the multiple liver metastases. Ten days later, he underwent rectal amputation including lymph node dissection combined with the implantation of reservoir for hepatic arterial infusion chemotherapy. After operation 5-FU (500 mg, days 1-5) and CDDP (10 mg, days 1-5) were injected for 3 weeks through hepatic arterial route. The metastatic lesions in the liver represented a good response to the chemolipiodolization, though the metastatic tumor in the liver S4 region did not disappear on CT scan. The histological diagnosis of the resected rectum revealed small cell carcinoma so we attempted additional chemotherapy according to the regimen for treatment of small cell lung cancer. ETP + CDDP therapy was performed, in which ETP (100 mg, days 1-3) and CDDP (80 mg, day 1) were intraarterially infused. After three courses of this therapy, he achieved a complete response (CR) for the liver metastasis. Two courses of ETP + CDDP therapy were additionally performed in the outpatient department, and treatment is currently continued by oral administration of ETP (75 mg/day). He has been free of the disease for 16 months with few side effects. The combination therapy of chemolipiodolization and hepatic arterial infusion chemotherapy with ETP and CDDP may assure a good prognosis for multiple liver metastases of small cell rectal cancer.     

Two cases of stage IV gastric cancer undergoing adjuvant surgery after down staging by chemotherapy

CASE 1: A 72-year-old man with epigastralgia was diagnosed with gastric cancer and referred to our hospital. An abdominal CT scan revealed liver metastasis and para-aortic lymph node metastasis. He was treated with S-1+CDDP. After 4 courses of this treatment, the liver metastasis and para-aortic lymph node metastasis disappeared, and adjuvant surgery was performed. There has been no recurrence for 16 months postoperatively. CASE 2: A 66-year-old man with anorexia was diagnosed with gastric cancer and referred to our hospital. An abdominal CT scan revealed para-aortic lymph node metastasis. He was treated with S-1+CDDP. After 9 courses of this treatment, para-aortic lymph node metastasis disappeared, and adjuvant surgery was performed. Eight months after the operation, lymph node metastases were confirmed by abdominal CT scan, and he was treated with chemotherapy as an outpatient as of 13 months after the operation. We experienced two cases of Stage IV gastric cancer undergoing adjuvant surgery after down staging by chemotherapy. It was suggested that adjuvant surgery to highly advanced gastric cancer could improve the prognosis of patients.     

A case of gastric cancer presenting with obstructive jaundice and responding to biweekly CPT-11 and CDDP combination administration

A 74-year-old man was suffering from Borrmann type 2 advanced gastric cancer with abdominal lymph node metastases and multiple lung metastases. He started to undergo outpatient treatment with oral administration of TS-1. But pyloric stenosis was found after 6 courses of TS-1 chemotherapy, so he underwent palliative distal gastrectomy. TS-1 chemotherapy was continued afterwards, however obstructive jaundice was found. So combination chemotherapy of CPT-11 60 mg/m(2)and CDDP 30 mg/m(2)biweekly was selected as a second-line therapy after PTCD. As no side effects were found, he could be treated on an outpatient basis by CPT-11 60 mg/body and CDDP 30 mg/body biweekly. Four months has passed since the palliative operation, and the PTCD tube was successfully removed. The abdominal lymph nodes had decreased in size and the patient has maintained good QOL. Thus, combination CPT-11 and CDDP therapy could well be a new candidate for a second-line chemotherapy in outpatients.     

A case of advanced gastric cancer found to be remaining by gastrectomy after a clinically complete response to chemotherapy

The patient was a 72-year-old woman diagnosed with advanced gastric cancer, hepatic portal lymph node and para-aortic lymph node metastases. After five courses of S-1/CDDP combination therapy, both the primary tumor and lymph node metastases disappeared clinically. She wished to continue chemotherapy instead of having a resection. After three more courses of S-1/CDDP therapy, gastric cancer and lymph node metastases were still completely regressed, but complications of carcinoma of the gallbladder were suspected. Gastrectomy was performed with cholecystectomy, and a histopathological examination revealed cancer cells remaining in the gastric submucosa and xanthogranulomatous cholecystitis. We consider surgical therapy for clinically completely disappearing advanced gastric cancer by chemotherapy, in addition to case report.     

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.     

A successful case with CPT-11 + CDDP chemotherapy for recurrent gastric cancer of the remnant stomach

We report a successful case with irinotecan (CPT-11 60 mg/m2) + cisplatin (CDDP 30 mg/m2) chemotherapy (once in 2 weeks) for recurrent gastric cancer of the remnant stomach. A 77-year-old man was performed a distal gastrectomy for duodenal ulcer 42 years ago. He had a total gastrectomy for gastric cancer of remnant stomach when he was at 73 years old. After the surgery, we treated this patient with S-1 mono-therapy for five courses. However, we finished this treatment for lymph-node metastases. Next we treated him with CPT-11 + CDDP. An abdominal CT revealed a CR after 6 courses. We finished this treatment after 12 courses for anemia (grade 3). After the treatment, the metastatic lymph-nodes appeared in no change. So we considered that CR was continued for 3.5 years.     

A recurrent endocrine cell cancer of the stomach showing almost complete remission after chemotherapy for 1 year

We report a recurrent case of gastric endocrine cell cancer that showed a remarkable response to systemic chemotherapy. A 70-year-old male who underwent gastroscopy at our hospital showed a 0-IIa-like lesion, but no abnormal CT findings. He was diagnosed with gastric cancer, and underwent a proximal gastrectomy. The resected specimen showed endocrine cell cancer. The tumor was Grimelius-positive histologically and chromogranin A-and NSE-positive immunohistochemically. About 2 years after surgery, liver, lymph node, and bone metastases were detected. Systemic chemotherapy with TS-1 and CDDP was started, and the lesions progressed. Then, by approximately 1 year after CDDP and CPT-11 treatments, the recurrent lesions had diminished remarkably and were no longer seen on CT or FDG-PET.     

Combination of operation, chemotherapy and radiation for AFP producing gastric cancer--a case report

We report a case of AFP producing gastric cancer after a combination of operation, chemotherapy and radiation. A 70-year-old man was admitted complaining of abdominal fullness. He was diagnosed as having type 3 advanced gastric cancer with multiple lymph node metastasis, including No. 8p lymph node, by endoscopy and computed tomography. Distal gastrectomy and D2 lymph node dissection were performed after chemotherapy using S-1, low-dose CDDP and CPT-11. Histopathological study showed moderately differentiated adenocarcinoma, and immunohistochemical study revealed a few AFP-positive tumor cells. Postoperatively, radiation (50 Gy) was performed for paraaortic lymph node metastasis and right hepatic lobectomy for liver metastasis. However, about 2 months after hepatic lobectomy, liver metastasis was diagnosed again by computed tomography, and radiation (30 Gy) was performed. He died 13 months after first surgery.     

A case of recurrent gastric cancer with lymph node metastasis successfully treated by CPT-11/CDDP therapy

We report a case ofa 76-year-old man suffering from advanced gastric cancer with lymph node recurrence. Distal gastrectomy was performed for gastric cancer with pylorus stenosis in April 2001. Pathological staging was III A(T3, N1, M0, Cur B). He underwent outpatient treatment with oral administration of UFT 400mg/day as postoperative adjuvant chemotherapy, but stopped after two months because of loss of appetite and general fatigue. Partial liver resection(S4/5)was performed for liver metastasis(S4)in June 2002, and S-1 was administered 80mg/day as adjuvant chemotherapy. However, obstructive jaundice was detected for lymph node recurrence in March 2003, and conducted bile duct stent after PTCD. He started to undergo a biweekly combination chemotherapy of irinotecan (CPT-11)60mg/m / 2 and cisplatin(CDDP)30mg/m2. Three months later, the lymph node had decreased in size. We reduced this therapy, extended the interval, and discontinued it after 24 courses due to adverse reactions, such as leucopenia(grade 3)and general fatigue(grade 2). Afterward, he had no recurrence for over 5 years.     

A case of AFP-producing gastric cancer resected after efficient S-1/CDDP combination chemotherapy

A 62-year-old male was diagnosed as AFP-producing gastric cancer with lymph node metastases and multiple liver metastases. He was treated with S-1 and CDDP combination chemotherapy. At the end of the first course, both primary and metastatic lesions were remarkably decreased in size, and the serum AFP level was also decreased. The chemotherapy was effective against the cancer and led to a partial response (PR) according to the RECIST guideline. Following the nine months of PR, the primary lesion which had once nearly disappeared, emerged again. Because distant lymph node metastases and liver metastases were considered to have disappeared, distal gastrectomy with D2 lymphadenectomy was performed. The patient received S-1 monotherapy for 6 months after the operation. At present the patient has achieved progression-free survival for 1 year and 3 months after the operation. Though AFP-producing gastric cancer is known for its poor prognosis, combination treatment such as operation or hepatic arterial infusion chemotherapy may improve the prognosis in patients with advanced AFP-producing gastric cancer when systemic chemotherapy is effective.     

A case of Stage IV gastric cancer with liver and peritoneal metastases responding completely to tailored S-1/CPT- 11 combination therapy

A 75-year-old man with advanced gastric cancer underwent distal gastrectomy with lymph node dissection(D1)and Roux-en Y reconstruction. Pathological staging was Stage IV (T3N3P1CY1M1), and curability was Cur C. He started adjuvant chemotherapy with oral administration of S-1(100 mg/body weight), but experienced grade 3 anorexia for one month. Abdominal computed tomography(CT)2 months postoperatively showed multiple liver metastases and ascites. We then conducted tailored S-1/CPT-11 as second-line chemotherapy(S-1 80 mg/body weight on days 1-5 and 8-12, CPT-11 60 mg/body weight on days 1 and 8). After 5 courses of this therapy, CT showed that the liver metastases and ascites had disappeared, leading to a complete response(CR). The only adverse event was general grade 1 fatigue. He continues to undergo oral administration of S-1(80 mg/body weight)as maintenance therapy, and maintained CR for 12 months since undergoing chemotherapy. Adverse events in tailored S-1/CPT-11 combination therapy are mild and tolerable, making this regimen a potential therapeutic strategy for patients with advanced or recurrent gastric cancer.     

A case of advanced gastric cancer showing a complete histological response after S-1/CDDP neoadjuvant chemotherapy

We experienced a case of advanced gastric cancer treated by curative operation after neoadjuvant chemotherapy with S-1/ CDDP. Gastric endoscopy was carried out on a 76-year-old man with epigastric discomfort and revealed a type 1 lesion in his stomach. Papillary adenocarcinoma was pathologically shown by endoscopic biopsy. The patient was initially treated by two courses of neoadjuvant chemotherapy with S-1/CDDP due to the large lymph node metastases around the lesser curvature of the stomach and celiac axis. Completion of chemotherapy resulted in a marked shrinkage of the primary lesion and a reduction of lymph node metastases. Later, total gastrectomy, splenectomy and D2 lymph node dissection were performed. Histopathological examination revealed no cancer cells in either the primary lesion of the stomach or dissected lymph nodes, confirming a pathologically complete response.     

A case of endocrine cell carcinoma of the esophagus successfully treated by chemoradiotherapy

The patient was a 74-year-old man who suffered from epigastric abdominal pain. He visited our hospital in April 2008. An esophageal endocrine cell carcinoma was pointed out by gastrointestinal endoscopy, and he was diagnosed as esophageal endoscopic cell carcinoma with mediastinum lymph node by CT scan(Stage IVa: cT3N4M0). Concurrent chemoradiotherapy using CDDP+EP was started. After two courses, the primary tumor was markedly reduced, and endoscopy showed only a scar. We diagnosed the patient as being in complete remission. However, CT showed a liver metastasis relapse in June 2009, and we started AMR as second-line chemotherapy. His general condition went into a decline, however, He died on October 2, 2009.     

A case of unresectable gastric cancer complicated by serious pyloric stenosis in which S-1 administration after gastrojejunostomy proved effective

We report a patient with unresectable gastric cancer who was effectively treated with S-1 after gastrojejunostomy. A 64-year-old man was referred to our hospital for anorexia and epigastric palpable mass. Upper gastrointestinal endoscopy revealed an ulcerous tumor in the antrum of the stomach, and gastric roentgenography showed pyloric stenosis. CT showed simultaneous multiple liver metastases. We performed gastrojejunostomy to allow oral intake. He was treated with daily oral administration of 120-80 mg S-1 for two weeks followed by one week rest as one course. The treatment was repeated for 19 courses until remission was observed. Weekly paclitaxel therapy (80 mg/m(2)/week) was then chosen as second-line chemotherapy. Administration was continued for three weeks with one-week rest. The treatment course was repeated for 6 courses. Bi-weekly administration of CPT-11 (80 mg) and CDDP (30 mg) was chosen as third-line chemotherapy. He died of progressive disease 2 years and 2 months after surgery. During chemotherapy, he maintained a performance status of 0 to 1, and maintained quality of life. This case suggested that the gastrojejunostomy was a useful method for treating unresectable gastric cancer, allowing the possibility of oral intake, and the use of S-1.     

A case of gastric cancer with multiple liver metastasis responding to combination therapy of CPT-11 and CDDP

A 63-year-old man suffering from advanced gastric carcinoma after distal gastric resection had multiple liver metastases 5 months after the operation. He underwent 3 courses of combination chemotherapy of 5-FU 600 mg/day with CDDP 50 mg/day, etoposide 100 mg/day and Leucovorin 30 mg/day for 5 days (FLEP), but progressive disease (PD) was noted. One additional course of combination chemotherapy with CPT-11 140 mg/day and CDDP 40 mg/day biweekly was performed and a complete response (CR) was noted. After 4 months, recurrence of a liver metastasis on S8 was demonstrated and 2 courses of the same chemotherapeutic regimen were carried out. Over 5 months, recurrence of the liver metastasis showed no change (NC) and resection of S8 of the liver was performed. No recurrence was after 6 months, but the patient died 34 months after the first detection of the occurrence of multiple liver metastases. The combination chemotherapy of CPT-11 with CDDP was also administered to other patients at our outpatient clinic and seems to be useful therapy for improving outcome.