A case of advanced gastric cancer responding remarkably to neo-adjuvant combination chemotherapy using CPT-11 plus S-1

Adjuvant chemotherapy for advanced gastric cancer has not yet been established. We report a patient with advanced gastric cancer responding remarkably to neo-adjuvant combination chemotherapy consisting of CPT-11 and S-1. The patient was a 69-year-old woman diagnosed with large type 3 advanced gastric cancer with esophageal invasion and having No.3 lymph node metastasis (cT3, cN1, cM0, cStage IIIA), treated with 2 courses of CPT-11 plus S-1 as neo-adjuvant chemotherapy. Computed tomography after neo-adjuvant chemotherapy showed improvement of gastric wall thickness and reduction of lymph node metastasis. Subsequently, she underwent an operation. There was no lymph node swelling,so we performed curative surgery consisting of total gastrectomy, splenectomy, cholecystectomy, and D 2 lymph node dissection. Histological diagnosis was pT2 (MP), pN1, pStage II, and estimation of the histological change by chemotherapy was Grade 2. The course after surgery was good, and she was treated by S-1 after discharge. To date, 8 months after surgery, there is no evidence of recurrence. Combination chemotherapy consisting of CPT-11 plus S-1 can be performed safely as a neo-adjuvant treatment, and may be an effective treatment modality for advanced gastric cancer.     

A case of complete response to S-1 plus CDDP in early-stage mucosal esophageal cancer

We report a case of early-stage mucosal esophageal cancer, showing a complete response to S-1 and cis-diamminedichloplatinum (CDDP). The patient was a 67-year-old man with synchronous double primary early-stage mucosal esophageal and advanced gastric cancer. We planned neoadjuvant chemotherapy with S-1 and CDDP for the advanced gastric cancer and endoscopic mucosal resection for the early-stage esophageal cancer. After the first course of chemotherapy, the endoscopy revealed that the esophageal cancer had become a normal mucosal lesion, and the biopsy was negative for cancer. We diagnosed a complete response to S-1 and CDDP in early-stage esophageal cancer. After two courses of chemotherapy, distal gastrectomy was performed. The patient is still alive with no sign of recurrence at 16 months after the disappearance of the original tumor. These results suggest that chemotherapy with S-1 plus CDDP may be effective in early-stage esophageal cancer.     

A case of long-term survival after resection of aortic arch for locally advanced non-small cell lung cancer with induction chemotherapy

Our patient was a 57-year-old male with a history of esophageal cancer. He was referred to our hospital for squamous cell lung carcinoma(SCC). Chest computed tomography identified a mass in the left lung field, which was suspected to be invading the reconstructed gastric tube, left subclavian artery, common carotid artery, and distal aortic arch. He was diagnosed as primary pulmonary squamous cell carcinoma(SCC)because six years had already passed since a previous surgery for early esophageal cancer. He received three courses of induction chemotherapy including S-1/CDDP. We evaluated the therapy as a partial response. He underwent an extended resection of distal aortic arch and left subclavian artery with left upper lobectomy, and those vessels were reconstructed using prosthetic grafts. Pathological findings showed the tumor as a well differentiated SCC of pT4N0M0 at stage III A, with a residual tumor on the reconstructed gastric tube, even though the effect of induction chemotherapy was Ef2. He received three courses of S-1/CDDP after surgery. The patient has been well without recurrence for 31 months after surgery.     

Pedunculated gastric tube interposition in an esophageal cancer patient with prepyloric adenocarcinoma

Gastric carcinoma is one of the malignancies that are most frequently associated with esophageal carcinoma.We describe herein our device for advanced esophageal cancer associated with early gastric cancer in the antrum.A 57-year-old man presenting with dysphagia and upper abdominal pain was admitted to our hospital.Preoperative examinations revealed locally advanced squamous cell carcinoma (SCC) of the middle thoracic esophagus (T3N0M0 Stage ⅡA) and mucosal signetring cell carcinoma of the gastric antrum (T1N0M0 Stage ⅠA).Although the gastric tumor appeared to be an intramucosal carcinoma,its margin was obscure,so endoscopic en-bloc resection was considered inadequate.We chose surgical resection of the gastric tumor as well as the esophageal SCC after neoadjuvant chemotherapy with 5-fluorouracil and cisplatin for advanced esophageal cancer.Following transthoracic esophagectomy with three-field lymph node dissection,the gastric carcinoma was removed by gastric antrectomy,which preserved the right gastroepiploic vessels,and a pedunculated short gastric tube was used as the esophageal substitute.Twenty-eight months after the surgery,the patient is well with no evidence of cancer recurrence.Because it minimizes surgical stress and organ sacrifice,gastric tube interposition is a potentially useful technique for esophageal cancer associated with localized early gastric cancer.     

Gastrojejunostomy followed by chemotherapy with S-1 in unresectable gastric cancer with pyloric stenosis

We investigated the efficacy of gastrojejunostomy followed by S-1-based chemotherapy for unresectable gastric cancer with pyloric stenosis. We performed gastrojejunostomy and S-1-based chemotherapy in 14 unresectable gastric cancer patients with gastric outlet obstructions between April 2006 and June 2010. Although there were two complications after surgery, no treatment-related deaths were observed. The response rate of the S-1-based chemotherapy was 41.7%, and the median survival after surgery was 12.3 months. All patients were tolerating a regular diet and a significant improvement in oral intake lasted for at least 6 months. In conclusion, gastrojejunostomy followed by chemotherapy with S-1 appears to be an effective treatment modality for unresectable gastric cancer with pyloric stenosis. It enables us to practice S-1-based standard chemotherapy for advanced gastric cancer and improve the quality of life of patients.     

替吉奥联合奥沙利铂治疗晚期食管癌近期疗效观察

目的 观察替吉奥联合奥沙利铂治疗晚期食管癌的近期疗效及不良反应.方法 30例晚期食管癌均接受化疗,替吉奥80mg/(m2 ·d),分2次,餐后口服,dl-14;奥沙利铂130 mg/m2,dl,静脉滴注＞3小时,21天为1周期,2周期后行胸腹部CT及消化道钡餐造影或胃镜评价疗效,并评价不良反应.结果 30例患者均可评价疗效,完全缓解(CR)0例,部分缓解(PR) 12例,病情稳定(SD)8例,病情进展(PD) 10例,有效率(CR+ PR)为40.0％,临床获益率(CR+PR+SD)为66.7％.中位疾病进展时间5月,1年生存率63.3％.主要不良反应为血液学毒性、消化道反应、肝功能损伤、皮疹、神经毒性等.结论 替吉奥联合奥沙利铂治疗晚期食管癌疗效较好,不良反应可耐受.     

Docetaxel plus S-1 as a second-line chemotherapy for metastasis or recurrence of esophageal cancer

Although chemotherapy consisting of cisplatin and 5-fluorouracil(CF)has been a standard regimen for esophageal cancer, it might be difficult to use continuously. This study evaluated the response and safety of docetaxel plus S-1 used as a second line therapy. We reviewed 21 patients(postoperatively, 11; after definitive chemoradiotherapy, 8; after chemotherapy, 2) who received chemotherapy between 2006 and 2010. Metastatic or recurrent disease was detected in the organs(n=8), lymph nodes(n=8), main tumors(n=3), mediastinum(n=1), and pleura(n=1). Docetaxel 30mg/m2 was infused every 2 weeks, and S-1 80mg/m2 was taken for 2 weeks, then with 2 weeks rest until progression. Almost all of the patients received docetaxel in the outpatient chemotherapy room. The median number of treatment cycles was 3, ranging from 1-12. Among the 14 patients with a therapeutic response, three(21%)achieved PR, 8 showed SD, and 3 had PD. Toxicity which included grade 3/4 was neutropenia in 6 patients, and anemia in one patient. After a follow-up of over one year, the median overall survival was 10 months, and the one-year survival rate was 38%. Docetaxel plus S-1 might be a feasible regimen as a second-line chemotherapy for metastasis or recurrence of esophageal cancer.     

Five cases of early gastric cancer in the reconstructed gastric tube after radical resection for esophageal cancer

We report seven early gastric cancers in five patients, which arose in the reconstructed gastric tube after radical resection for esophageal cancer. Four of them occurred in the middle gastric tube and three in the distal gastric tube. Three of 5 cases were reconstructed via the retromediastinal route and two via the presternal route. They all were diagnosed by follow-up endoscopy from 8 months to 5 years after esophagectomy. All of them were treated surgically with partial resection of the gastric tube because they were suspected to have invaded the submucosal layer or large enough to be treated with endoscopic mucosal resection (EMR). Histologically, six of seven were diagnosed as well differentiated adenocarcinoma and one as signet ring cell carcinoma. Although one of them died for reasons other than cancer itself, the others are alive and well without any recurrence. Recently, gastric tube cancer after esophagectomy has been increasingly reported to be accompanied with prolongation of survival of esophageal cancer patients. Total or partial gastrectomy is proposed for surgical treatment of gastric tube cancer, but the operating procedure is complicated and invasive, especially in the case of gastric tube reconstructed via the retromediastinal route. Total gastrectomy is much more invasive because it needs re-reconstruction with other organs. Therefore, it is important to detect the lesion in early stages so as to treat it with minimally invasive surgery such as EMR or partial resection. Hence intensive follow up with endoscopy is necessary after resection of esophageal cancer.     

A carcinoma of the reconstructed gastric tube after a radical esophageal cancer operation

Reported are five patients who developed a carcinoma of the reconstructed gastric tube. In 3 of the 5 patients, the esophageal cancer was preceded by a gastric cancer, and the intervals before the gastric cancer was detected were 34, 24, and 60 months. The gastric tube the had been reconstructed by the retrosternal rout was resected with a median sternotomy in cases 1 and 2. In case 3, since a liver and lung metastasis had been detected by routine examination, surgery was not performed. Cases 4 and 5 had an esophageal cancer associated with a simultaneous early gastric cancer located in the lesser curvature of the upper body. Thus, a esophagectomy and a partial gastrectomy were performed. Twenty-eight and 21 months later, respectively, an early gastric cancer was found at the stump of the gastric tube that had been reconstructed by the retrosternal route. Endoscopic laser therapy was subsequently employed for both patients. Because of these findings, the author have concluded that postoperative serial examination of the gastric tube are very important, since cases of a gastric tube cancer are increasing.     

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.     

Two cases of stage IV gastric cancer responding to chemotherapy with S-1 or UFT

We report patients with advanced Stage IV gastric cancer responding to chemotherapy with S-1 or UFT. Case 1: The patient was a 59-year-old man with Stage IV gastric cancer because of CY 1. After surgery, chemotherapy with S-1 (100 mg/body/day) was performed for one year and 11 months. At present, 5 years and 5 months after surgery, this patient shows no signs of tumor recurrence. Case 2: The patient was a 68-year-old woman with Stage IV gastric cancer because of P 1. She was treated with 200 mg/day of UFT for one year and 9 months. At present, 5 years after surgery, she shows no signs of tumor recurrence. We considered that the longterm survival of such patients is attributable to chemotherapy with S-1 or UFT. The OPRT activity of the two cases was high, so chemotherapy with S-1 or UFT was thought to be effective for them.     

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 esophageal cancer with intramural metastasis demonstrates a good clinical course after induction chemotherapy followed by chemoradiation

A 63-year-old man with dysphagia visited our hospital in February 2007. Esophagogastroduodenoscopy and computed tomography revealed that he suffered from advanced esophageal cancer with intramural metastasis at clinical stage III (T3N1). The patient underwent induction chemotherapy because he had great difficulty deciding which treatment would be more beneficial for him use dash surgery or chemoradiation. The reason for his in decision was that esophageal cancer with intramural metastasis is known to have a poor prognosis after surgery, and although chemoradiation is the more attractive therapy that avoids invasive surgery, it is very difficult to predict a response. Currently, he has survived for more than 3 years with no recurrence, after chemoradiation that followed a good response to induction chemotherapy. This result suggested that induction chemotherapy followed by chemoradiation can be one of the useful strategies for patients who have esophageal cancer with a negative prognosis factor for surgery, such as intramural metastasis.     

Pilot study of intraperitoneal administration of paclitaxel and oral S-1 for patients with peritoneal metastasis due to advanced gastric cancer

Background  There is no standard treatment for peritoneal dissemination from gastric cancer. A novel combination chemotherapy has been introduced for patients with advanced gastric cancer with peritoneal metastasis. Methods  This pilot study was performed on four patients to confirm safety and efficacy. They were diagnosed with unresectable gastric cancer with severe peritoneal dissemination by staging laparoscopy, or with metastasis to the transverse colon. We selected combined chemotherapy with both paclitaxel and S-1. Paclitaxel at 60 mg/m² or 60 mg/body was administered intraperitoneally on days 1 and 8 and S-1, at 80–120 mg/body, was administered orally for 14 days followed by 7 days’ rest, as one course. After five courses of this therapy, the primary gastric tumors were evaluated by conventional examinations, and second-look laparoscopy was performed to assess the efficacy of the treatment against the peritoneal metastases. Results  After five courses, primary tumor reductions were confirmed, and no cancer cells were detected on pathocytological investigation during second-look laparoscopy in any of the patients. Three patients underwent total gastrectomy with lymph node dissection and one underwent left upper abdominal evisceration. Final histological staging showed two stage 3 and two stage 4 patients. The intraperitoneal administration of paclitaxel and the oral administration of S-1 were well tolerated. Three patients died, at 8, 15, and 29 months, respectively, after the initial treatment, and one has been alive for 54 months without recurrence. Conclusion  This chemotherapy can be used in the treatment of patients with peritoneal metastasis of gastric cancer.     

A patient with esophageal cancer recurrence responding to S-1 combined with cisplatin (CDDP)

We administered a combination chemotherapy of S-1 plus cisplatin (CDDP) therapy to a patient with recurrenced cancer of esophagus in lymph node. S-1 (80 mg/m(2)/day), taken out of the capsule, was administered via the catheter for tube feeding on day 1 to day 21 and CDDP at 60 mg/m(2)/day by intravenous drip infusion on day 8 for 3 weeks followed by a drug-free 2 week period as the first course. After 2 courses, CT findings showed a complete regression of the lymph node for complete response (CR). He has been alive for 10 months without recurrence. Combined use of S-1 and CDDP is effective as chemotherapy for recurrenced esophageal cancer.     

Preliminary trial of adjuvant surgery for advanced gastric cancer

In patients with stage IV gastric cancer, systemic chemotherapy is the key treatment. Combination chemotherapy (cis-diamminedichloride platinum plus S-1 and docetaxel plus S-1) results in long-term survival in clinical practice. In selected cases, additional (adjuvant) surgery may result in further long-term survival. This study aimed to evaluate the efficacy of adjuvant surgery following the response to chemotherapy for advanced gastric cancer. Based on response to chemotherapy, the indications for adjuvant surgery (surgery after the response to chemotherapy) are that resection is expected to be curative rather than palliative, provided that no other distant metastases occur. The study included 20 advanced gastric cancer patients who had undergone gastrectomies after the response to the combination chemotherapy of docetaxel and S-1, between September 2003 and December 2008 at Hiroshima University Hospital. At a median follow-up of 980 days, the median overall survival was 855 days. A 2- and 3-year survival was observed in 80 and 54.9% of patients, respectively, following macroscopic curative surgery. In the palliative group, the median overall survival was 510 days, but a 3-year survival was not observed. In the partial response group, the median overall survival was 865 days and a 3-year survival was observed in 37% of patients. One-year survival was not observed in the stable disease group. The patient survival in the partial response group was statistically more prolonged than in the stable disease group. The median overall survival in patients with liver metastasis was 865 days, while that in patients with peritoneal dissemination was 510 days. In conclusion, adjuvant surgery may be effective in gastric cancer patients diagnosed as stage IV by means of liver or distant lymph node metastasis, except in cases of peritoneal dissemination.     

Usefulness of S-1/gemcitabine combination therapy for advanced pancreatic cancer

Combination chemotherapy with S-1 and gemcitabine(GEM)was given to patients with advanced pancreatic cancer and favorable results were obtained. These patients were 77-(Stage IVa), 68-(Stage IVb), and 64-year-old males (Stage IVb). They were administered S-1 at a dose of 80-100 mg/day for 2 weeks and GEM at a dose of 1,000-1,200 mg/body on days 8 and 15 followed by a 2-week recovery period. One course consisted of a 2-week treatment period and a recovery period; this course was repeated in all of these patients. The 3 types of patients have survived for a year and five months, a year and three months, and nine months, respectively, after diagnosis. In the first patient, who was in Stage IVa, the primary cancer has been maintained in a reduced state without metastasis. In the other two patients, who were in Stage IVb, the primary cancer and hepatic metastatic lesions have been reduced remarkably. Quality of life is good in all the patients. Combination therapy with S-1 and GEM can be provided for a long-term treatment with few adverse reactions on an outpatient basis. Based on the changes in tumor markers, we observed that the inhibitory effects of this combination chemotherapy are immediate and persistent with long-term treatment. Therefore, we expect S-1/GEM combination therapy to be the chemotherapy of choice for advanced pancreatic cancer.     

Chemoradiotherapy for esophageal cancer

Since mucosal (T1a) esophageal cancer is well controlled by endoscopic treatment, chemoradiotherapy (CRTx) is not indicated. However, for a submucosal (T1b, N0) esophageal cancer, CRTx may be the first line of treatment, since it can provide a good response rate, with an excellent survival rate comparable to that after esophagectomy. Definitive CRTx is also in the first line of treatment for a T4 esophageal cancer, because there was no difference in the survival rate between CRTx with surgery and CRTx without surgery in our trial. Esophagectomy is indicated only for non-responders or recurrence-salvage surgery. For patients with a potentially-resectable (T2-T3) esophageal cancer, esophagectomy offered a longer survival rate than CRTx did, in our series. However, there remains controversy over the efficacy of CRTx for a T2-T3 esophageal cancer. It has been reported by the National Cancer Center Hospital East Group that definitive CRTx provided the same survival rate as esophagectomy. A prospective trial comparing the survival rate after esophagectomy and that after CRTx for a T2-T3 esophageal cancer is needed.     

A case of unresectable gastric cancer presenting pylorus stenosis treated orally with S-1 therapy after gastrojejunostomy

We reported a case of unresectable gastric cancer presenting pylorus stenosis treated orally by S-1 therapy in a 72-year-old man who underwent gastrojejunostomy. He was admitted to our hospital complaining of appetite loss and body weight loss. Detailed examination showed gastric cancer with pylorus stenosis. After insertion of the naso-gastric tube with washing, a laparotomy was done. The operative findings revealed sT3, sN2, sP1, sH0 and sM1 (metastases of No. 14a lymph nodes invading the super mesenteric artery and pancreas) as an unresectable case with stage IV. Gastrojejunostomy and Braun anastomosis were made through the antecolic route. After the operation, intake therapy of S-1 was started (80-100 mg/body/dayx28 days). After 2 courses of the therapy, gastrointestinal fiber showed clinically a partial response of the main tumor. After 3 courses of this treatment, the tumor presented multiple liver metastases as a clinically progressive disease state. Paclitaxel therapy was conducted at a dose of 80 mg/body/weekx3 timesx2 courses. The patient had no effective benefits from the treatment and died of the cancer. He had survived 9 months, and the intervals of the intake and home stay were 7.5 months and five months, respectively, after the operation with no side effect of the chemotherapy. Survival was no longer than for patients only operated without S-1 therapy.     

A case of long survival of a scirrhous gastric cancer patient with esophageal invasion and peritoneal dissemination through chemotherapy and palliative surgery

We report a case of advanced scirrhous gastric cancer treated by operation and chemotherapy for over four years. The patient was a 54-year-old female who had suffered from gastric cancer with esophageal invasion. She underwent total gastrectomy with D2 dissection. Operative findings revealed peritoneal dissemination, and it resulted in non-curative resection. After surgery, combination chemotherapy with low-dose CDDP administered intraperitoneally and S-1, combination chemotherapy with paclitaxel and 5-FU, and then combination chemotherapy with docetaxel and S-1 were sequentially performed. She also underwent palliative surgery for intestinal obstruction resulting from carcinomatous peritonitis. She achieved long survival with good quality of life(QOL)by multidisciplinary therapy of chemotherapy and surgical operation.