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 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 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.     

A case of multi-drug resistant breast cancer with liver metastasis treated effectively by S-1 monotherapy

We report a case of multi-drug-resistant breast cancer with liver metastases which completely responded and improved the quality of life (QOL)by S-1 monotherapy. The patient was a 53-year-old woman, who was diagnosed as breast cancer with invasive chest wall, cervical lymph node metastases, multiple bone metastases and bilateral pleural effusion[invasive ductal carcinoma, scirrhous type, ER(-), PgR(+), HER2(1+)]. After six courses of cyclophosphamide+epirubicin(CE)and weekly paclitaxel for 3 months, cervical lymph node metastasis was judged as a partial response(PR)and the bilateral pleural effusion disappeared. After chemotherapy, aromatase inhibitor (AI) was used. However, primary lesion and multiple bone metastases no change(NC). Following pass through AI+ oral anticancer drug combination chemotherapy and oral anticancer drug monotherapy, the therapy was changed to palliative, and she was referred to our hospital in January 2007. On arrival at the hospital, respiratory distress and bilateral pleural effusion had appeared, so it was an emergency admission. After removing the pleural effusion, pleurodesis was done and the symptoms disappeared. Although AI plus bisphosphonate therapy were started at hospital discharge, disease progression and fatigue appeared. In December 2007, we started S-1 monotherapy. S-1 was given orally at 80 mg/m2 for day 1-28 followed by a 2-week rest period, within a 6-week courses. Six months after treatment was started, multiple liver metastases disappeared and peritoneal effusion decreased. During the period of S-1 treatment, there were no serious adverse events, and treatment was possible without compromising QOL. This result suggested that S-1 treatment was a reasonable option for multi-drug-resistant breast cancer.     

A case of advanced gastric cancer responding to S-1 therapy, leading to pathologically complete response

Our patient was a 74-year-old man with abdominal pain. A gastrofiberscope revealed type 2 advanced gastric cancer. An abdominal computed tomography(CT)demonstrated liver and lymph node metastases. The No. 8a lymph node was 7 cm in diameter, and it invaded the head of the pancreas. Since a curative operation was deemed impossible, S-1 was administered orally for 28 consecutive days with a 14-day interval. After 2 courses of monotherapy, CT showed that metastatic lymph nodes were reduced and that liver metastases had mostly disappeared. After 8 courses, the primary lesion was scarred and the lymph node metastases were remarkably reduced. Therefore, we conducted distal gastrectomy and lymph node resection (D2). Histological findings revealed that there were no cancer cells in either the primary tumor or the lymph nodes, meaning that the resected lesions were Grade 3 in pathology. This rare case showed that S-1 monotherapy enabled curative surgery of unresectable gastric cancer with pathological CR.     

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.     

Successful bi-weekly paclitaxel treatment of an AFP-producing gastric cancer patient with peritoneal dissemination and multiple liver metastasis

The patient was a 71-year-old man. Chemotherapy was conducted in two courses combining TS-1 (120 mg) and CDDP (80 mg) under the diagnosis of AFP-producing gastric cancer with multiple liver metastasis and peritoneal dissemination. Peritoneal dissemination disappeared, liver metastasis almost disappeared after completion of two courses, and the therapeutic efficacy was rated as PR. Then, the patient underwent distal gastrectomy and lymph node dissection. He received TS-1 monotherapy after surgery, but his condition gradually became worse. TS-1 and CDDP combination were given again, but an ileus resulted due to peritonitis carcinomatous. We therefore administered bi-weekly paclitaxel (80 mg/m(2)) intravenously. The ileus disappeared after one week, liver metastatic lesions and ascites were improved after completion of one course, and therapeutic efficacy was rated as PR. Grade 3 neutropenia and grade 1 alopecia occurred, but no other adverse reaction occurred. This therapy made it possible to eat foods, conduct chemotherapy safely while ambulatory. Paclitaxel can be expected to show good therapeutic efficacy and improve QOL of a peritonitis carcinomatosa patient with TS-1 resistant advanced gastric cancer.     

A case of long-term survival after undergoing S-1 based multidisciplinary therapy for liver metastasis of gastric cancer

We encountered a case of gastric cancer accompanied with liver metastasis, which had a good response to chemotherapy of S-1. A 68-year-old female was admitted to our hospital due to further examination of gastric tumor detected by an outpatient physician. She was found to have a type-3 gastric cancer in upper gastrointestinal endoscopy and a metastatic tumor of the liver in abdominal CT. Although chemotherapy of S-1 was inducted for the lesions, both the primary and liver tumors were dramatically reduced. We subsequently performed total gastrectomy and partial hepatectomy. Abdominal CT scan at 11 months after the initial operation revealed metachronous liver metastasis. She received combination chemotherapy of S-1 and CDDP. After 5 courses of the combination chemotherapy, the liver tumor disappeared. She has survived for 8 years without a recurrence after the initial operation. There was negative findings of immunostaining with thymidylate synthetase (TS), which was target enzyme for 5-FU at a biopsy sample of the primary gastric tumor before chemotherapy of S-1. TS immunostaining may be a useful marker for S-1 combined therapy for gastric cancer associated with liver metastases.     

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.     

Long-term survival of patient with gastric cancer treated by S-1 + paclitaxel combination chemotherapy against multiple liver metastases after gastrectomy and adrenalectomy

The patient was a 74-year-old man whose chief complaint was epigastralgia. A detailed examination revealed a gastric cancer located from antrum to duodenal bulb with multiple liver metastases. Because of a difficulty with oral intake, we performed a distal gastrectomy at first. After the operation, a combination chemotherapy with S-1 and weekly paclitaxel was performed, and liver metastases were successfully disappeared after 4 courses of the regimen. A subsequent CT evaluation after 6 courses of the regimen revealed that liver metastases maintained the clinical complete response (cCR), but a right adrenal tumor was detected. We performed a right adrenalectomy after 13 months from gastrectomy, and a histopathological examination revealed that the adrenal tumor was a recurrent gastric cancer. After the second operation, only one course treatment of S-1 alone was performed because the patient rejected the chemotherapy. The patient is alive without a chemotherapy and maintained cCR for 75 months after the second operation.     

Highly advanced gastric cancer that responded to neoadjuvant combination chemotherapy with docetaxel/CDDP/S-1 (DCS)

A 60-year-old male was found to have advanced gastric cancer and multiple lymph node metastases. Since curative surgery was concluded to be unfeasible, we tried neoadjuvant chemotherapy with the aim of controlling the lymph node metastasis. S-1 (80 mg/m2) was administered orally for two weeks then followed by 2-week rest period. CDDP (60 mg/ m2) and docetaxel (40 mg/m2) were simultaneously administered on day 1. Two courses of treatment resulted in marked shrinkage of the primary lesion and a reduction in size of the lymph nodes. The results were evaluated as a clinical PR based on RECIST, and radical resection was considered possible. The patient experienced a grade 3 leukocytopenia and neutropenia as adverse events of the chemotherapy. Total gastrectomy, splenectomy, and D2 lymph node dissection were performed with curative intent, and the postoperative course was uneventful. Histological examination of the surgical specimens revealed almost complete disappearance of cancer cells in the primary lesion in the stomach and complete disappearance in the lymph nodes. Pathological efficacy was Grade 2. The patient experienced a grade 3 appetite loss, and the adjuvant chemotherapy (S-1 regimen) was discontinued. The patient died of peritoneal dissemination eight months after the operation. We concluded that DCS as neoadjuvant chemotherapy was a promising strategy for patients with highly advanced gastric cancer because of its rapid antitumor effect.     

Successful treatment of advanced gastric cancer by surgical resection following combination chemotherapy with oral S-1 and biweekly paclitaxel

We report on the successful treatment of advanced gastric cancer by surgical resection following neoadjuvant chemotherapy. A 67-year-old man was referred to our hospital with a diagnosis of pancreatic cancer. Meticulous examination, however, revealed the presence of gastric cancer with ascites and large lymph node metastasis adjacent to the pancreas. We selected combination chemotherapy with oral S-1 and biweekly paclitaxel. After two courses, both the primary tumor and metastatic lymph nodes were greatly reduced, and the ascites had disappeared. Using laparoscopy, there was no evidence of peritoneal metastases, and the cytological examination was negative. The patient underwent distal gastrectomy with D2 lymph node dissection. Histological examination revealed that the cancer cells were still present in part, but no lymph node metastases were found. The tumor was pathologically diagnosed as pT2, pN0, P0, M0, CY0, and p-stage II. The patient is healthy over 4 years after surgery without recurrence.     

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 synchronous gastric and hepatocellular carcinoma successfully treated by TS-1 and hepatic arterial infusion chemotherapy (HAI) of low-dose CDDP

A 75-year-old man underwent distal gastrectomy for advanced gastric cancer with liver and lymph node metastases and synchronous hepatocellular carcinoma in April 2004. HAI with low-dose CDDP/TS-1 combination therapy was initiated after gastrectomy. Liver and lymph node metastases decreased significantly, with achievement of a partial response (PR) and a complete response (CR), respectively, and the hepatocellular carcinoma was reduced to 54.1% of its initial size after 3 sessions of this chemotherapy. These results suggested that combined chemotherapy with TS-1 and HAI with low-dose CDDP was not only useful for liver and lymph node metastases from gastric cancer, but for hepatocellular carcinoma as well.     

A case of advanced gastric cancer successfully treated with S-1 and paclitaxel followed by curative resection

A 59-year-old man diagnosed with Stage IV advanced gastric cancer due to pancreatic invasion(T4)and splenic hilum lymph node metastasis(N3)was initially treated with neoadjuvant chemotherapy using S-1 and CDDP. However, it was discontinued because the tumor marker increased after 1 course. Instead of S-1 and CDDP, S-1 and paclitaxel were then administered. After 4 courses, CT scan revealed reduced tumor size and the disappearance of splenic hilum lymph node swelling that indicated PR of the chemotherapy. Moreover, serum CEA was remarkably decreased to 77 ng/mL from 1,092 ng/mL. He could undergo subtotal gastrectomy(Billroth II)with lymph node dissection(D2)and cholecystectomy. Histopathological examination revealed Stage II (pT2(SS), pN1, CY0, ly1, v2)advanced gastric cancer that showed good effect of S-1 and paclitaxel. At this writing (October 2007), the patient has remained free of disease for more than 1 year and 6 months with good nutrition. Neoadjuvant chemotherapy using S-1 and paclitaxel for advanced gastric cancer seems to have been effective.     

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 advanced gastric cancer with multiple bone metastases and distant lymph node metastases successfully treated by S-1/CDDP combination chemotherapy

We describe a 46-year-old man who presented with the chief complaint of lower back pain. The patient was diagnosed with advanced gastric cancer accompanied by multiple bone metastases, with compression fractures in the thoracolumbar vertebrae as well as distant lymph node metastases. He was administered eight courses of S-1/CDDP combination chemotherapy. Treatment results were as follows: primary lesion, non-CR/non-PD; lymph node metastases, CR; and bone metastases, non-CR/non-PD. As only the primary lesion showed a tendency toward progression after completion of eight courses, distal gastrectomy with D1 dissection was performed. Histopathological test results were ypT1b(SM1)and ypN1(2/22). The histological grade following treatment was grade 2 for both the primary lesion and the lymph nodes Following subsequent treatment with S-1 monotherapy and zoledronic acid, the disease did not progress, and at one year and four months since diagnosis and six months since surgery, CR and non-CR/non-PD have been maintained for the lymph node metastases and bone metastases, respectively.     

A case of advanced gastric cancer with Virchow's and paraaortic lymph node metastases successfully resected after combined chemotherapy of low-dose CDDP and 5-FU

The patient was a 61-year-old woman who had Stage IV advanced gastric cancer with Virchow's and paraaortic lymph node metastases. The lesions were considered surgically incurable, so she was placed on neoadjuvant chemotherapy consisting of low-dose CDDP and 5-FU. After 3 courses of chemotherapy, the tumor had decreased remarkably in size and Virchow's metastasis had disappeared. She was considered to have a partial response (PR) and underwent distal gastrectomy. Histopathological examination of the primary tumor revealed that almost all cancer cells existed in the mucosal and submucosal layers; few had infiltrated the serosa. A few paraaortic lymph nodes were positive for metastasis, but a curative resection (Cur B) was performed. The patient received another course of chemotherapy after the operation. Low-dose CDDP and 5-FU therapy was associated with few adverse events in this case, and thought to be effective against advanced gastric cancer.     

A case of gastric cancer with liver metastasis had a good reaction to S-1/CDDP chemotherapy after S-1 chemotherapy was ineffective

A woman in her sixties underwent total gastrectomy for gastric cancer. The pathological diagnosis was pT3, pN3, sH0, pCY0, sP0, sM0, fStage IV. Chemotherapy with S-1 was used after surgical treatment. Because a CT scan after three courses chemotherapy showed the paraaortic lymph nodes swelling, combination chemotherapy with S-1 and docetaxel was used as a second-line chemotherapy. When the CT scan after 8 courses of this combination chemotherapy revealed multiple liver metastases, the chemotherapy was changed to CPT-11 monotherapy and paclitaxel monotherapy as the third-and fourth-line chemotherapy, respectively. In spite of those chemotherapies, the metastatic disease progressed, and therefore, combination chemotherapy with S-1 and CDDP was used as the fifth-line chemotherapy. After 6 courses of this treatment, serum CEA and CA19-9 levels dropped into the normal range. Multiple liver metastases were markedly reduced, and were considered as a partial response(PR). The patient is still alive, maintaining the effect of PR for 17 months without any adverse effects except appetite loss and vomiting of grade 2.     

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.