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 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 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.     

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 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 gastric adenosquamous carcinoma with abdominal paraaortic lymph node metastases successfully treated by TS-1 plus CDDP neoadjuvant chemotherapy

A 62-year-old woman was admitted for anemia. An endoscopic examination revealed type 2 cancer from the upper body of the stomach to the antrum, and abdominal CT scan demonstrated enlarged abdominal paraaortic lymph nodes. The preoperative diagnosis was cStage IV gastric cancer (cT 3, cN 3, cH 0, cP 0, cM 0). Since a curative operation was deemed impossible, we conducted neoadjuvant chemotherapy using TS-1 plus cisplatin (CDDP) for downstaging. TS-1( 100 mg/day) was orally administered for 3 weeks,and CDDP (60 mg/m2) was given intravenously on day 8. Appetite loss of grade 3 and erythropenia of grade 1 were observed. After two courses of chemotherapy the primary lesion and the paraaortic lymph nodes were significantly reduced in size. She was judged as clinical PR, followed by distal gastrectomy and lymph node dissection, resulting in curability A. Histopathologically, the tumor was diagnosed as adenosquamous carcinoma of the stomach with lymph node metastasis at only No.3. This case suggests that neoadjuvant chemotherapy using TS-1 plus CDDP is effective for advanced gastric adenosquamous carcinoma with massive lymph node metastases.     

A case of advanced gastric cancer with liver metastases successively treated with S-1/CDDP combination therapy followed by curative resection

The patient was a 67-year-old male with type-3 gastric cancer from the upper body of the stomach to the cardia. An abdominal computed tomography scan revealed liver metastases(S8)(T2N0M0H1, Stage IV). The patient received neoadjuvant combined chemotherapy with S-1 and CDDP. S-1(120mg/body/day)was orally administered for 3 weeks followed by 2 drug-free weeks as a course, and CDDP(60mg/m2)was administered by intravenous infusion on day 8. After the second course, significant tumor reduction and disappearance of liver metastases resulted. Total gastrectomy, splenectomy, cholecystectomy, and D2 nodal dissection were performed. The histological diagnosis revealed no metastases in all lymph nodes: Stage I B. The combined neoadjuvant chemotherapy with S-1 and CDDP can be considered an effective treatment for advanced gastric 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.     

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.     

A case of advanced gastric cancer which became operable after chemotherapy with combination of TS-1/CDDP and in which complete disappearance of liver metastasis was histopathologically confirmed

We encountered a patient in whom TS-1/cisplatin (CDDP) combination chemotherapy was effective. The cancer became operable, and complete disappearance of liver metastasis was histopathologically confirmed. The patient was a 65-year-old man who presented with complaints of epigastric discomfort and anorexia. Based on upper GI endoscopy and abdominal CT, type 1 gastric cancer associated with liver and abdominal lymph node metastases was diagnosed. The cancer was judged to be inoperable, and chemotherapy with a combination of TS-1 and CDDP was initiated. One course of treatment consisted of administration of 120 mg/day of TS-1 for 21 days followed by 14 days of withdrawal, and administration of 100 mg/body/day of CDDP on day 8 (80 mg/body/day in the second course). After two courses of treatment, the primary lesion and the liver and lymph node metastatic lesions decreased in size (reduction ratios were 42.3%, 90.5% and 85.2%, respectively). The tumor marker values became normal. Subsequently, the cancer was judged to have become operable. After consultation with the patient, total gastrectomy, splenectomy, partial hepatectomy, and D3 dissection were performed, and curability B was achieved. The only adverse event of Grade 2 or more severity observed during drug administration was anorexia. Liver metastasis was judged from pathological findings to have disappeared. The postoperative course was uneventful and the patient was discharged from the hospital. To date, there have been no signs of recurrence. TS-1/CDDP therapy is believed to provide effective treatment against liver metastasis and lymph node metastasis of gastric cancer.     

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 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.     

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.     

A case of gastric cancer with abdominal paraaortic lymph node metastases responding to TS-1 plus CDDP neoadjuvant chemotherapy

A 62-year-old woman was admitted because of epigastralgia and tarry stool. An endoscopic examination revealed type 3 cancer in the lower body of the stomach, and abdominal CT scan demonstrated enlarged abdominal paraaortic lymph nodes. The preoperative diagnosis was cStage IV gastric cancer (cT3, cN3, cH0, cP0, cM0). Since a curative operation was deemed impossible, we started neoadjuvant chemotherapy using TS1 plus cisplatin (CDDP) for downstaging. TS-1 (100 mg/day) was orally administered for 3 weeks, and CDDP (90 mg/body) was administered intravenously on day 8. Appetite loss of grade 3 and leucopenia of grade 1 were observed. After two courses of chemotherapy, the primary lesion was reduced in size, and the paraaortic lymph nodes disappeared on abdominal CT scan. The serum tumor marker became normal. Subsequently, she underwent curative total gastrectomy with splenectomy and lymph node dissection. Histological examination of the primary lesion revealed marked fibrosis and a small amount of residual cancer cells. The histological changes by neoadjuvant chemotherapy were judged to be grade 2 for the main tumor. It is suggested that neoadjuvant chemotherapy using TS-1 plus CDDP is effective for advanced gastric cancer with massive lymph node metastases.     

A patient with gastric cancer and liver metastases successfully treated with combination chemotherapy including S-1

We report the case of a 62-year-old man with advanced gastric cancer and multiple liver metastases who was successfully treated with combined chemotherapy including S-1. The patient was clinically diagnosed with stage IV (T3 N2 H1 P0) disease and was initially treated with 100 mg/body per day S-1 administered orally for 21 days and 10 mg/body per day cisplatin (CDDP) infused on days 1–5, 8–12, and 15–19. This chemotherapy resulted in significant reduction of the liver and gastric tumors. After receiving additional CDDP/S-1 administration as an outpatient, the patient's liver masses disappeared as shown on abdominal computed tomography (CT). With the patient's desire and informed consent, he underwent curative surgery with total gastrectomy, D1+α lymph node dissection, and partial resection of liver S4. After discharge without any surgical complication, CT revealed regrowth of the S4 liver mass, and combined docetaxel and CDDP was selected as second-line chemotherapy with local radiation therapy against the hepatic metastasis. Additionally, a third regimen with irinotecan and S-1 was given. At 2 years 7 months after the initial treatment, no sign of cancer (including liver metastasis and peritoneal dissemination) has been identified by radiological follow-up examinations.     

A patient with stage IVb small cell carcinoma of the esophagus who survived 23 months after systemic cancer chemotherapy

A 59-year-old male visited our hospital with complaints of difficulty in swallowing. X-ray barium studies and upper gastrointestinal endoscopic examination revealed an irregular ulcerated lesion in the lower portion of the esophagus, which was diagnosed based on pathology tests as small cell carcinoma. A computed tomography scan showed para-aortic lymph node swelling and multiple liver metastases. Treatment with chemotherapy of CDDP and 5-FU showed clinical complete remission. However, the patient died of paraaortic lymph node metastasis, recurrence of the original lesion, multiple liver metastasis and brain metastasis 23 months after diagnosis. The prognosis of small cell carcinoma of the esophagus is quite unfavorable because of the highly aggressive biological behavior. However, if remission is achieved by chemotherapy as in this case, a better prognosis is possible.     

A case of multiple para-aortic lymph node metastases from squamous cell carcinoma of an unknown primary responding completely to chemotherapy

We report a case of disease -free survival with combination chemotherapy against squamous cell carcinoma(SCC)of an unknown primary. A 54-year-old male had an intraabdominal malignant lymph node tumor beside the common hepatic artery which was revealed by image studies including CT, MRI and PET-CT. After extirpation of the tumor, the resected specimens were diagnosed as metastatic SCC in the lymph nodes by pathology and immunohistochemistry. Cancers of an unknown primary are divided into two sub-groups, favorable and unfavorable, based on their clinical output. During hesitation to cure because of the unfavorable sub-group, the authors recognized multiple Virchow's and para-aortic lymph node metastases in this case. However, chemotherapy with CDDP/5-FU, followed by S-1, and then DOC were effective, resulting in a CR. The patient has been well without any sign of recurrence over 3 years after the first chemotherapy and about 2 years after the last chemotherapy. If a primary site is not found immediately after careful detection cancer of an unknown primary should be cured.     

A case of advanced gastric cancer with peritoneal dissemination responding to S-1/CDDP neoadjuvant chemotherapy

The patient was a 72-year-old male diagnosed with type III poorly-differentiated adenocarcinoma in the lesser curvature by gastric fiberscopy. An abdominal computed tomography (CT) scan showed the thickness of the gastric wall and the enlarged lymph node around the stomach and laparoscopic examination revealed peritoneal dissemination. The patient received neoadjuvant combined chemotherapy with S-1 and CDDP. S-1 (100 mg/day) was orally administered for 3 weeks followed by 2 drug-free weeks as a course, and CDDP (100 mg/body) was administered by intravenous drip on day 8. After the third course, significant tumor reduction was obtained. Total gastrectomy, splenectomy and D2 nodal dissection were performed. Peritoneal dissemination disappeared, and the histological diagnosis revealed complete disappearance of cancer cells in the ascites and no metastasis in all lymph nodes. The patient has now been in good health with no recurrence for 22 months after surgery. The combined neoadjuvant chemotherapy with S-1 and CDDP can be an effective treatment of choice for advanced gastric carcinoma with peritoneal dissemination.     

Pathological complete response in advanced gastric carcinoma by S-1/CDDP combination chemotherapy

A59 -year-old woman was referred to our hospital for a close examination and treatment of an advanced gastric carcinoma. A physical examination and CT scan showed that the right cervical and axillar lymph nodes were swelling, and a histopathological examination of the axillar lymph node revealed metastatic growth of the gastric carcinoma (Stage IV). Then, we started S-1/CDDP combination chemotherapy. S-1 (80 mg/m2/day)was orally administered for 3 weeks followed by 2 weeks of rest, and CDDP (60 mg/m2) was administered by drip on day 8. Since the distant metastases were greatly reduced after 6 courses of combination therapy, a distal gastrectomy with lymph nodes dissection (D2) was performed. Histopathological examination of the resected tissues revealed no residual cancer cells, suggesting a pathologically complete response. The clinical course after the operation went well without any complications, and the patient is alive with no evidence of recurrence 1 year after surgery. S-1/CDDP combination chemotherapy appears to be one of the effective treatments for advanced gastric carcinoma.     

Histological complete response in a case of advanced gastric cancer treated by chemotherapy with S-1 plus low-dose cisplatin and radiation

A 76-year-old male was diagnosed with stage IV (cT4, cN2, cP0, cH0, cM0) gastric carcinoma with a type 3 tumor in the cardia with lymph node metastases, determined by gastrofiberscope and abdominal computed tomography (CT). The patient was treated with chemotherapy consisting of S-1 and low-dose cisplatin (CDDP) during the first cycle (3 weeks). S-1 was orally administered at a dose of 100 mg/day (60 mg/m(2)/day) on days 1-21. CDDP was infused at a dose of 10 mg/day (6 mg/m(2)/day) on days 1-5, 8-12 and 15-19. After this cycle, the clinical response was evaluated as no change (NC). In the second cycle, radiation therapy (2 Gy/day for 5 days/week) was initiated along with the chemotherapy. The CDDP dose was decreased to 7.5 mg/day because of the grade 3 thrombocytopenia and grade 2 leukocytopenia that occurred during the first cycle. The second cycle was stopped at a total radiation dose of 48 Gy due to grade 3 thrombocytopenia and grade 2 leukocytopenia. Examination after this treatment showed remarkable reduction of tumor volume in the primary lesion and lymph nodes, which was defined as a partial response (PR). The patient then underwent total gastrectomy with D1 lymph node dissection. The postoperative course was uneventful without surgical complications. At this time, no gastric cancer cells were detected in the resected specimen, including the primary lesion and lymph nodes, confirming a pathological complete response (CR grade 3). Thus, the chemo-radiation treatment regimen described here may be a potent tool to control advanced gastric carcinoma.