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 report of metastatic neuroendocrine carcinoma of the right adrenal gland successfully treated with chemotherapy and surgery

Poorly differentiated neuroendocrine carcinoma has a poor prognosis, especially when associated with distant metastasis. A 60-year-old man was admitted to a private hospital because of dyspnea at work in 2007. Computed tomography revealed lung infarction and a right adrenal tumor sized 12 cm in diameter that was tightly compressed against the inferior vena cava (IVC). Moreover, multiple lymph node metastases around the celiac axis and a solitary liver metastasis at the lateral segment were observed. Thus, we planned chemotherapy without surgery. We selected a combination therapy of irinotecan (CPT-11) and cisplatin (CDDP) (i.e., IP therapy): administration of CDDP [60 mg/m² body surface area (BSA)] on day 1 plus CPT-11 (80 mg/m²) BSA on days 1 and 8. Thereafter, this protocol was repeated at 3-week intervals. After 15 months of this chemotherapy strategy, the whole lesions showed a partial response by RECIST. The primary tumor had shrunk to 4.2 cm in diameter. In November 2008, we planned surgery to perform resection of the whole lesions. Histological diagnosis of the specimen was a poorly differentiated neuroendocrine carcinoma based on the immunostaining features, i.e., synaptophysin- and chromogranin positive. There were no viable tumor cells at the dissected lymph nodes or at the liver tumor. After surgery, CPT-11 administration was continued. The patient has remained well for 9 months 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.     

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 successful control for primary duodenal cancer with combined CPT-11, CDDP and DOC chemotherapy

We have experienced a rare case of primary duodenal carcinoma with perforation of the duodenum. Combined CPT- 11, CDDP and DOC chemotherapy achieved a partial response. A 54-year-old man with serious abdominal pain visited our hospital with a diagnosis of acute peritonitis due to perforation of digestive tract on CT scan. An emergency operation was performed with patch for perforation of the duodenum. Endoscopic examination and biopsy after surgery showed duodenal adenocarcinoma. Abdominal CT scan revealed metastasis to the periaortic lymph nodes. Therefore, we diagnosed primary duodenal carcinoma with metastasis to the periaortic lymph nodes. Combined CPT-11, CDDP and DOC chemotherapy were performed. After two courses, endoscopic examination and biopsy showed primary lesion of the duodenum had disappeared. Metastatic lymph nodes were reduced from CT scan after three courses, and successfully controlled until nine courses. Then regimen was changed to S-1 alone and S-1/CPT-11. The patient remained alive for two years after the operation without tumor progression.     

A case of successfully treated sigmoid colon cancer with multiple regional metastases by chemotherapy and radiation therapy

Multiple regional metastases due to colon cancer usually show poor prognosis. Various treatments such as chemotherapy and radiation therapy are not sufficient, and the outcome is generally poor in many cases. We report here on a patient with multiple regional metastases who was successfully treated with several therapies and remains still alive. A 69-year-old man presented with fever and epigastralgia. A colonoscopy revealed primary sigmoid colon cancer. A computed tomography showed multiple hepatic metastases, and metastases to supraclavicular, mediastinal and para-aortic regional lymph nodes. The bone metastases were detected by scintigram. He was treated with combination chemotherapy of 5-FU via hepatic artery and CPT-11 by systemic administration. The primary tumor had completely disappeared (complete response), and metastases to liver and lymph nodes showed a remarkable shrinkage (partial response) after the chemotherapy. In contrast, bone metastases showed progressive growth (progressive disease). Radiation therapy and bisphosphonate infusion for bone metastases were achieved, and the treatments have controlled the growth of the metastases. Primary tumors and metastases are still controlled well for 3 years after the initial chemotherapy.     

Extra- and intra-hepatic metastasis successfully treated with alternative chemotherapy with hepatic arterial infusion and systemic intravenous infusion after responding to hepatic metastasis from colon cancer by hepatic arterial infusion--a case report

A 72-year-old woman, who had the carcinoma of cecum with unresectable multiple liver metastases, underwent ileocecal resection and insertion of hepatic arterial infusion catheter. Hepatic arterial infusion (HAI) chemotherapy using Leucovorin. 5-FU caused to decrease liver metastases after an initiation of HAI. However, the metastatic nodule at the right lobe of lung was found. Then systemic chemotherapy with CPT-11 CDDP was performed alternately with HAI chemotherapy. After the initiation of revised regimen, all metastatic lesions were shrunk. We here in present the case of extra- and intra-hepatic metastasis successfully treated with alternative chemotherapy with hepatic arterial infusion and systemic intravenous infusion after responding to hepatic metastasis from colon cancer by hepatic arterial infusion.     

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 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 gastric cancer with liver metastases successfully treated with combination therapy of systemic and hepatic arterial infusion chemotherapy

A 67-year-old man was admitted to our hospital because of advanced gastric cancer associated with metastases to the liver, the lymph nodes along the lesser curvature and the infradiaphragmatic lymph nodes. As we considered the primary lesion and the liver metastases to be unresectable, we treated him with combination therapy of systemic and hepatic arterial infusion chemotherapy. The regimen of systemic chemotherapy consisted of cisplatin (CDDP) and UFT. Hepatic arterial infusion chemotherapy included 5-fluorouracil (5-FU), doxorubicin (DXR) and mitomycin C (MMC). We repeated this therapy six times. The size of the primary lesion and the lymph node metastases decreased significantly after the chemotherapy. The size of the liver metastases did not change, but they appeared to necrotize. The patient maintained a good quality of life during the therapy. He finally died of peritonitis carcinomatosa 18 months after the diagnosis. This case indicated that combination therapy of systemic and hepatic arterial infusion chemotherapy was effective in cases of unresectable gastric cancer associated with liver metastases.     

A case of multiple lung and liver metastases from colon cancer treated with clinical benefit by hepatic arterial infusion chemotherapy plus cetuximab mono-therapy after standard chemotherapy failure

We report a case of multiple lung and liver metastases from colon cancer treated with clinical benefit by hepatic arterial infusion chemotherapy plus cetuximab mono-therapy after a standard chemotherapy was failed. A 61-year-old female who had sigmoid colon cancer with unresectable multiple lung and liver metastases underwent sigmoidectomy. Bevacizumab plus mFOLFOX6 was performed as first-line therapy. Partial response was obtained temporarily. After the first-line therapy failed, bevacizumab plus FOLFIRI as second-line, and cetuximab plus CPT-11 as third-line therapy were performed. Since these regimens did not work, her performance status got worse by cholangitis due to progressive liver metastases and anemia. Hepatic arterial infusion chemotherapy for liver metastases and cetuximab for lung metastases as fourth therapy were chosen because we thought her liver metastases should be critical for the maintenance of her QOL and diagnosis. After that, serum CEA was reduced from 14,715 to 6,940 ng/mL during the 3 month period. And her performance status got better as cholongitis and anemia were improved. Additionally, lung metastases were controlled by cetuximab.     

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 advanced gastric cancer with multiple liver metastases successfully treated with TS-1 and CDDP

A Case of Advanced Gastric Cancer with Multiple Liver Metastases Successfully Treated with TS-1 and CDDP: Akihiro Tsukahara, Kazuhiro Kaneko and Syuji Tanaka (Dept. of Surgery, Niigata Prefectural Koide Hospital) Summary A 70-year-old advanced gastric cancer patient with liver and lymph node metastases was treated by chemotherapy with TS-1 and CDDP. One course consisted of administration of TS-1 100 mg/body for 21 days followed by 14 days rest and infusion of CDDP 80 mg/body on day 8. At the end of 2 courses, the primary tumor showed a hypertrophic wall, but a partial response of the liver metastases (reduction ratio was 78.3%) and a complete response of the LN metastasis were achieved. PR and CR were maintained after 4 courses. There were no remarkable side effects for 4 courses. This chemotherapy may have therapeutic efficacy in cases of advanced gastric cancer with liver and lymph node metastases.     

A case of small cell carcinoma of esophagus treated by chemotherapy with CDDP plus CPT-11 and radiotherapy

We present a case of small cell carcinoma of esophagus treated by chemotherapy with CDDP plus CPT-11 and radiotherapy. A 73-year-old woman visited our hospital with complaints of neck mass and discomfort during swallowing. Upper gastrointestinal endoscopy revealed a type 3 tumor in the middle portion of the esophagus, which was pathologically diagnosed as small cell carcinoma. A computed tomography showed lymph node swelling from neck to mediastinum. Then she was administered chemotherapy with CDDP plus CPT-11 and radiotherapy. The main tumor and lymph node swelling was remarkably reduced by chemoradiotherapy. The prognosis of small cell carcinoma of the esophagus is extremely poor because it may cause a general metastasis in early stage. This case was for long-term survival with chemoradiotherapy, and we report our case with the literature cited.     

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 advanced gastric cancer with multiple liver metastases responding completely to hepatic arterial infusion and systemic chemotherapies

A 41-year-old male complaining of epigastric discomfort visited another hospital for a medical checkup. Gastrointestinal fiberscopic examination revealed a type 3 lesion on the lesser curvature of the lower portion, and biopsy specimens showed tubular adenocarcinoma. Abdominal CT demonstrated multiple liver metastases. After receiving a low-dose FP chemotherapy via IVH catheter for 1 week, the patient undertook a distal gastrectomy accompanied by D2 lymph node dissection. From the 19th postoperative day (POD), hepatic arterial infusion chemotherapy (HAIC) using 5-FU (500 mg/day) plus CDDP (10 mg/day) was performed for about 14 months. On the 47th POD, oral administration of UFT began and continued for 2 years. After 4 months of HAIC, the metastatic lesions of the liver disappeared completely. The patient has been free from recurrence since then for about 2 years. In the peripheral blood, Th1/Th2 ratio and activity of NK/LAK (IL-2 induced) kept increasing during this period. IHAC using 5-FU plus CDDP seems to be an efficient and worthy therapeutic modality if there are no other lesions except multiple liver metastases and a curative gastric resection is indicated.     

Arterial infusion therapy with low-dose cisplatin and continuous 5-fluorouracil for isolated hepatic recurrence of gastric carcinoma

Patients with metachronous liver metastasis after curative resection of gastric carcinoma generally have a poor prognosis, even when recurrence is confined to the liver. We report a patient in whom hepatic arterial infusion therapy with bolus low-dose cisplatin (CDDP) and continuous 5-fluorouracil (5-FU) was effective against large metastases confined to the liver. An 83-year-old man was admitted with huge liver metastases from gastric carcinoma. Intra-arterial bolus injection of low-dose CDDP (5 mg) and continuous intra-arterial infusion of 5-FU (250 mg/day for 7 days) was started. After four courses of this arterial infusion therapy, computed tomography scans revealed shrinkage of the liver metastases. He was followed-up as an outpatient and continued to receive the arterial infusion therapy once every 4 weeks. Throughout the course of the chemotherapy, a partial response of the liver metastases was maintained. The patient had an improved quality of life after starting the chemotherapy, and he survived for 16 months from the commencement of the therapy. Arterial infusion therapy with bolus low-dose CDDP and continuous 5-FU may be recommended for patients with isolated hepatic recurrence of gastric carcinoma. Received: September 6, 1999 / Accepted: January 31, 2000     

A case of advanced gastric cancer responding to neoadjuvant TS-1/CDDP therapy

A 62-year-old advanced gastric cancer patient with bulky N2 lymph node metastases was treated by neoadjuvant chemotherapy with TS-1 and CDDP. TS-1 (100 mg/body/day) was orally administered for 3 weeks followed by a drug-free 2-week period as 1 course, and 75 mg/body/day of CDDP was administered by intravenous drip on day 8. After the first course, the primary lesion and the regional lymph node metastases showed partial response in terms of size. No serious drug adverse reaction was observed. During the second course, urgent total gastrectomy with distal pancreatectomy and splenectomy was performed for massive bleeding from a deep gastric peptic ulcer. The histopathological findings showed complete response of the carcinoma as primary lesion except for two sites of minimal lymphatic permeation and one lymph node (No. 8a) metastasis. The combined use of TS-1 and CDDP is useful as neoadjuvant chemotherapy for advanced gastric cancer.     

A case of remnant liver metastases after resection of liver metastases from rectal cancer following treatment with 5-FU, L-OHP and CPT-11, with markedly effective treatment by cetuximab plus S-1

FOLFOX or FOLFIRI are commonly used as first- or second-line chemotherapy for unresectable colorectal cancer or its metastases.Recently, it had become a trend to add bevacizumab or cetuximab(Cmab)limited to the K-ras wild-type or panitumumab(Pmab)limited to the K-ras wild-type.At the present time, a common third-line chemotherapy is CPT-11 plus Cmab limited to the K-ras wild-type, or Cmab/Pmab.However, the results are unsatisfactory.With Cmab plus S-1 we treated a case of remnant liver metastases from rectal cancer which was a K-ras wild-type, after treating 5-FU, L-OHP and CPT-11. The tumor marker dropped and 7 focuses of liver metastases disappeared after 6 courses of treatment(complete response: CR in)and CR was achieved after 9 courses treatment.After 10 courses of treatment, a new lesion appeared on S5 of the liver and we performed percutaneous radiofrequency ablation.     

Second-line chemotherapy with bi-weekly CPT-11 and cisplatin for recurrent colorectal cancer resistant to 5-FU based chemotherapy

Second-line chemotherapy with bi-weekly CPT-11 and cisplatin (CDDP) was given to 19 patients with recurrent colorectal cancer resistant to 5-FU based chemotherapy. The 19 patients consisted of 18 men and 1 woman with a mean age of 61.3 years. Nine patients had liver metastasis, 4 had lung metastasis, 2 had local recurrence, 2 had both local recurrence and lung metastasis, respectively, 1 had local metastasis and lymph node metastasis, and 1 had bone metastasis. CPT-11 (80 mg/m2) and CDDP (30 mg/m2) were administered bi-weekly. The objective overall response rate was 15.8%. The time to progression was 146 days, and the median survival time was 477 days. Grade 3 leucopenia and nausea occurred in 1 patient (5.3%). CPT-11 and CDDP treatment should be considered as second-line chemotherapy for colorectal cancer resistant to 5-FU based chemotherapy.