A case of gastric cancer with liver metastasis responding to low-dose CDDP/5-FU combination chemotherapy

We reported a case of a 62-year-old female with gastric cancer accompanied by liver, Virchow and paraaortic lymph nodes, and bone metastasis (taken low-dose cisplatin (CDDP)/5-fluorouracil (5-FU) combination chemotherapy). CDDP (10 mg/body/day) was injected on 1-5 days i.v. and 5-FU (500 mg/body/day) was injected i.v. continuously on 1-7 days. This treatment cycle was repeated for 4 weeks. After 4 cycles, liver metastasis disappeared without severe side effects. Primary lesion and Virchow's lymph nodes metastasis were reduced. However, bone and paraaortic lymph node metastasis showed no response. It was considered that low-dose CDDP/5-FU combination chemotherapy was effective for liver and lymph nodes metastasis of gastric cancer in this case.     

A case of advanced cancer with liver metastasis and paraaortic lymph node metastasis responding remarkably to combination chemotherapy of low-dose CDDP, 5-FU and CPT-11

A 57-year-old male patient with upper epigastric discomfort was introduced to our hospital from another clinic because of gastric cancer. Several examinations showed massive liver metastasis and paraaortic lymph node metastasis from Type-3 gastric cancer beneath the posterior wall of the pyloric antrum. First we tried infusion of CDDP (10 mg/day for days 1-5 and 8-12) and continuous infusion of 5-FU (500 mg/day for 14 days). Concurrently, we added infusion of CPT-11 (80 mg/day on days 1,8). After 3 courses of chemotherapy, the tumor had decreased remarkably in size. Moreover, liver metastasis and paraaortic lymph node metastasis had vanished. This regimen thus appears to be effective for advanced gastric carcinoma.     

An oral anticancer drug, TS-1, enabled a patient with advanced gastric cancer with Virchow's metastasis to receive curative resection

We encountered a patient with advanced gastric cancer, with Virchow's lymph node metastasis, who subsequently underwent curative resection after neoadjuvant chemotherapy with the newly developed oral anticancer drug, TS-1. The patient was a 67-year-old woman who had a type 2 tumor in the middle third of the stomach, and Virchow's lymph node metastasis, which was diagnosed by fine-needle aspiration cytology; she also had swollen paraaortic lymph nodes. Curative resection was considered impossible, and TS-1 (100 mg/day) was administered for 28 days in one course, mainly in the outpatient clinic. Although grade 2 stomatitis interrupted the therapy on day 21 of the second course and on day 7 of the third course, the type 2 tumor showed marked remission (partial response; PR) and the metastasis in the Virchow's and paraaortic lymph nodes had completely disappeared after the third course (complete response; CR). Eleven weeks after the completion of the TS-1 treatment, total gastric resection with D3 lymph node dissection was performed. Histopathological examination revealed tumor involvement only in the mucosal and submucosal layers of the stomach and the no. 4d lymph node. Most of the tumor was replaced with fibrosis with granulomatous change in the muscularis propria of the stomach and in the no. 3, no. 6, and no. 7 lymph nodes. This may be the first report of a patient with advanced gastric cancer with Virchow's lymph node metastasis who successfully received curative resection following neoadjuvant chemotherapy with a single oral anticancer drug. Received: August 7, 2001 / Accepted: January 28, 2002     

A case of advanced gastric cancer with liver and intra-abdominal lymph node metastasis treated by hypertensive selective chemotherapy with pharmacokinetic modulating chemotherapy

There have been few effective chemotherapeutic regimens for advanced gastric cancer with liver and intra-abdominal lymph node metastasis. A 78-year-old male patient was admitted to our hospital because of anorexia and abdominal discomfort. Gastroendoscopy showed a type 4 advanced gastric cancer in the antrum of the stomach. Histological study of biopsy specimens from the tumor revealed poorly differentiated adenocarcinoma. Examination by computed tomography and ultrasonography showed swollen paraaortic lymph nodes and liver metastasis. He was diagnosed as having advanced gastric cancer with liver and lymph node metastasis. This patient was treated weekly with an intraarterial 5-FU (500 mg) and MTX (100 mg) including AT-II by subcutaneously implanted port system placed into the celiac artery. Furthermore, he was administered tegafur/uracil (400 mg/day) 5 days weekly as pharmacokinetic modulating chemotherapy (PMC). After ten courses of treatment with PMC, the liver and lymph node metastases were reduced in size. This therapy was considered to be an effective treatment for advanced gastric cancer with liver and lymph node metastasis. The theoretical purpose of hypertensive chemotherapy used together with injection of angiotensin-II is to increase the delivery of anticancer drug to the target tumor tissue by increasing the blood flow in the tumor. We conclude that this chemotherapy is effective in cases of advanced gastric cancer with liver and lymph node metastasis from the viewpoints of toxicities, antitumor effect and QOL of the patient.     

A case of advanced colon cancer with metastases to both the Virchow's and the paraaortic lymph nodes that achieved complete long-term response with levofolinate.5-FU therapy

A 48-year-old woman presented with a tumor in the supra-clavicular fossa. Under a diagnosis of advanced ileocecal colon cancer with metastases to Virchow's and the paraaortic lymph nodes, ileocecal resection was performed. After surgery, the patient was given 5-FU infused continuously at 500 mg/body per day, and levofolinate was dripped intravenously at 100 mg/body over 2 hours for 5 successive days per week. Two cycles were repeated each week. She was then intravenously given weekly modulation chemotherapy consisting of 125 mg/body levofolinate and 500 mg/body of 5-FU for about 5 months on an outpatient basis. Furthermore, the same administration schedule was continued bi-weekly for 1 year and 4 months. As a result, the enlarged paraaortic lymph nodes had completely disappeared by 5 months after administration of levofolinate.5-FU. The Virchow's lymph node metastasis has not been palpable for 11 months. Throughout the period of treatment, there were no severe side effects and as of this writing, no sign of recurrence for 3 years after surgery. A high quality of life has been maintained. In conclusion, this case seems significant from the viewpoint of the complete long-term response to a moderate dose of levofolinate.5-FU therapy and the long duration of administration, which was tolerable with few side effects. Moreover, we identified the presence of TS and DPD using immunohistochemical staining techniques, when both primary tumor and regional lymph nodes were all negative for the stain test. It was suggested that this cancer especially would responded to 5-FU chemotherapy.     

A case of nonresectable scirrhous type gastric cancer treated by hypertensive subselective chemotherapy with pharmacokinetic modulating chemotherapy

There have been few effective chemotherapeutic regimens for scirrhous type gastric cancer. A 62-year-old male patient was admitted to our hospital because of anorexia and abdominal discomfort. Gastroendoscopy showed a type 4 advanced gastric cancer in the upper gastric body. Histologic study of biopsy specimens from the tumor revealed poorly differentiated adenocarcinoma. Examination by computed tomography and ultrasonography revealed swollen paraaortic lymph nodes and peritonitis carcinomatosa. The patient was diagnosed as having a nonresectable scirrhous type gastric cancer with peritonitis carcinomatosa and paraaortic lymph node metastasis. This patient was treated weekly with an intraarterial 5-FU (500 mg) and MTX (100 mg) including AT-II by a subcutaneously implanted port system placed into the thoracic aorta. Furthermore, he was administered tegafur/uracil (400 mg/day) 5 days weekly as a pharmacokinetic modulating chemotherapy (PMC). After eight courses of treatment of PMC, paraaortic lymph node swelling and ascites decreased. This chemotherapy produced a partial response in the peritonitis carcinomatosa and paraaortic lymph nodes. This chemotherapy was repeated preoperatively. We reconsidered this case to show indications for operation. The patient died suddenly of acute heart failure before the operation. This therapy was considered an effective treatment for nonresectable gastric cancer.     

A case report of gastric carcinoma with complete remission of paraaortic lymph node metastasis by 5'-DFUR and MMC administration after resection of primary tumor

A 53-year-old man was referred to our hospital with Borrmann type 2 advanced gastric cancer with a Virchow's node metastasis. A CT scan revealed a paraaortic lymph node metastasis. Because the tumor was diagnosed as being a poor candidate for curative resection, only a total gastrectomy was done. After surgery, administration of 5'-DFUR and MMC was begun. As a result, the paraaortic lymph node metastasis disappeared and the Virchow's node metastasis was reduced. The patient is well with no sign of recurrence 20 months after the operation.     

A case of recurrent gastric cancer that responded dramatically to docetaxel and 5'-DFUR combination chemotherapy

A 54-year-old man suffering from Borrmann type 4 advanced gastric cancer with pancreatic invasion and paraaortic lymph node metastases underwent a total gastrectomy, which was a radical C operation. From postoperative month 4, he visited our hospital with multiple liver metastases and increased lymph node metastases. After chemotherapy with CDDP and 5-FU, CDDP and UFT was administered on an outpatient basis. The effect of this therapy was PD, therefore, docetaxel and 5'-DFUR combination chemotherapy was performed as second line therapy. After 2 courses of this therapy, the size of liver and lymph node metastases was reduced and the effect of this therapy was PR. The patient has undergone 4 courses of this therapy and is maintaining a clinical PR. It is conceivable that docetaxel and 5'-DFUR combination chemotherapy is useful for patients with advanced and recurrent gastric cancer, even if they had been treated with 5-FU administration as first line therapy.     

A case of advanced gastric cancer that responded to docetaxel with low-dose 5-FU and cisplatin combination chemotherapy after becoming chemoresistant to M-FLP

We report a case of advanced gastric cancer that responded to docetaxel with low-dose 5-FU and cisplatin combination chemotherapy after becoming chemoresistant to M-FLP. A 52-year-old male was diagnosed with type 3 gastric cancer of angulus (poorly differentiated adenocarcinoma) with left neck, Virchow, mediastinal and abdominal lymph nodes metastases. The patient was treated with 5 courses of M-FLP (MTX + 5-FU + LV + CDDP), and the effect of this therapy was PR, but the tumor was chemoresistant to the sixth course of this therapy. After 7 courses of M-FLP, docetaxel (TXT) with low-dose FP (5-FU + CDDP) was administered to the patient as second-line chemotherapy. After 2 courses of TXT with low-dose FP, the gastric cancer and metastatic lymph nodes were remarkably reduced and the effect of this therapy was PR. The toxic events were anemia (grade 2) and leukopenia (grade 3), which were treated with G-CSF. CDDP and 5-FU based regimens are considered as the first-line chemotherapy for metastatic advanced gastric cancer in Japan; however, a second-line chemotherapy has not been established. As in this case, a TXT based regimen is effective and well tolerated therapy as a second-line chemotherapy for metastatic gastric cancer after prior exposure to CDDP and 5-FU.     

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.     

Pathological evaluation of neoadjuvant chemotherapy with low-dose FP therapy for advanced gastric cancer

In the present study, we evaluated the pathological effects of preoperative chemotherapy with low-dose CDDP and 5-FU (low-dose FP therapy) in patients with advanced gastric cancer. 50 patients diagnosed as advanced gastric cancer were administered continuous infusion of 5-FU (300 mg/m(2)/day, x 14 days) and intermittent infusion of CDDP (3 mg/m(2)/day, day 1-5 and 8-12) before surgery. The pathological effects were considered comparatively regarding the response rate of chemotherapy for gastric cancer between primary lesions and metastasis of lymph nodes and the rate of downstaging cases with low-dose FP therapy. The rates of effective cases were 26% (primary lesions) and 28% (lymph nodes). Furthermore,in the same patient,the results of low-dose FP therapy with primary tumor were more effective than those of lymph nodes (the rates of effective cases were 34% and 19%, respectively). The rate of downstaging cases with low-dose FP therapy for gastric cancer was 6%, histologically. These results indicate low-dose FP therapy for gastric cancer is promising for effective clinical management of advanced gastric cancer in preoperative treatment.     

Curative resection of advanced gastric cancer responding to preoperative chemotherapy--a case report

A 56-year-old male was admitted for treatment of advanced gastric cancer. The patient was diagnosed as having an unresectable advanced gastric cancer because cancer cells had invaded the pancreas head and there were metastatic lymph nodes. The patient underwent preoperative chemotherapy (FLEP: intra-arterial infusion of CDDP, ETP and intravenous infusion of 5-FU, LV). The primary tumor and metastatic lymph nodes were reduced by three course of chemotherapy. The patient underwent curative resection and survived without recurrence for 14 months after operation. Preoperative chemotherapy using FLEP was performed in 15 patients with unresectable primary advanced gastric cancer. This therapy resulted in significantly higher survival times. In conclusion, FLEP has been shown to be effective for unresectable advanced gastric cancer.     

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.     

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 curatively resected AFP producing gastric cancer with massive lymph node metastasis effectively treated by neoadjuvant-chemotherapy of S-1 and CDDP

A 65-year-old man who had AFP producing gastric cancer with massive lymph-node metastasis was admitted to our institution. Because of bulky lymph-node metastasis, the tumor was considered unresectable. He was treated with neoadjuvant chemotherapy of S-1 and cisplatin (CDDP).S-1 (80 mg/m2/day) was administered for 21 consecutive days followed by 14 days rest as one course,and CDDP (60 mg/m2) was infused over 2 hours on day 8. After 1 course, radiographic examination showed remarkable improvement in the tumor size of the stomach, and computed tomography showed markedly reduced paraaortic lymph node metastasis. However, surgery was performed after 3 weeks,because of the adverse effect of diarrhea grade 3 after one course of the chemotherapy. This is a rare case in which neoadjuvant chemotherapy of S-1 and CDDP may well be an effective treatment for unresectable AFP producing gastric cancer with bulky lymph-node metastasis.     

A case of unresectable advanced gall bladder cancer successfully treated by hepatic arterial chemotherapy with reservoir (HACR) using CDDP and 5-FU

A 64-year-old female was admitted for treatment of a huge tumor (10 cm in diameter) in segment S4-S5 of the liver. The lymph node (2 cm in diameter) was located posterior to the pancreas head. The patient was diagnosed with an unresectable advanced gall bladder cancer with direct invasion of the liver bed and lymph node metastasis. At first, hepatic arterial infusion of CDDP, MMC and ADM through the hepatic artery was performed. Then, hepatic arterial chemotherapy with reservoir (HACR) using CDDP and 5-FU (CDDP 20 mg/body/day, 5-FU 750 mg/body/day) was started. As a result, the primary tumor and enlarged lymph node almost disappeared in two years. Mild bone marrow suppression, nausea and vomiting were encountered, but no severe side effects were noted. We conclude that this strategy is effective for unresectable advanced cancer of the gall bladder with lymph node metastasis.     

A case of advanced gastric cancer with giant lymph node metastasis responding to S-1/CDDP neoadjuvant chemotherapy

The patient was a 66-year-old man with advanced gastric cancer and bulky lymph node metastases. Since a radical resection appeared impossible, we tried neoadjuvant chemotherapy(NAC)with S-1/CDDP, expecting down staging of the tumor. S-1(120 mg/body)was orally administered for 21 days and CDDP(40 mg/body)was administered by intravenous drip on day 8, 15 and 22. Partial response(PR)was obtained after 2 courses, and distal gastrectomy with D2 lymph node dissection was performed. The histological diagnosis revealed complete disappearance of cancer cells in stomach and a few regional lymph node metastasis(3/30). The patient was administered S-1 for one year after operation, and he is well without recurrence at one year and four months postoperatively. We considered the S-1 and CDDP in combination useful as preoperative chemotherapy for advanced gastric cancer.     

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.     

Complete response of a highly advanced gastric carcinoma to preoperative chemoradiotherapy with S-1 and low-dose cisplatin

S-1 has been developed as a new oral anticancer drug, based on the biological modulation of 5-fluorouracil. We report a patient with highly advanced gastric carcinoma who was treated successfully with a new combination chemoradiotherapy using S-1 and cisplatin (CDDP). The patient was a 37-year-old man who was diagnosed with advanced gastric carcinoma (T4N3M0) that had invaded the diaphragm and the paraaortic tissues. Remarkable tumor reduction was observed in the primary tumor and metastatic lymph nodes around the stomach after three cycles of the therapy. Radiological examination before surgery determined that a partial response (PR) had been achieved by the initial therapy. Adverse effects included only a gastrointestinal disorder that was limited to grade 2 when low-dose CDDP was utilized in the regimen, while an initial high dose of CDDP resulted in grade 3 toxicity, due to myelosuppression. The patient underwent curative surgery, including total gastrectomy, D2 lymph node dissection, and splenectomy, after completion of the radiochemotherapy regimen. No surgical complication was observed. No tumor cells were detected by pathological evaluation of the resected stomach and all the regional lymph nodes, confirming a pathological complete response (CR; grade 3). This regimen is a potent treatment for advanced gastric carcinoma, especially when used as preoperative chemotherapy to control cancer cells.     

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.