Published papers

Background CXCL-8, known as proinflammatory cytokine interleukin (IL)-8, and its receptor, CXCR-2, are expressed in various cancer cells. CXCL-8/CXCR-2 network is believed to be involved in angiogenesis, growth, and invasion of tumor cells. To date, the clinical significance of CXCL-8/CXCR-2 network in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we investigated the role of CXCL- 8/CXCR-2 network in ESCC. Methods The subjects included 78 patients with primary ESCC. We examined CXCL-8 and CXCR-2 expression in surgically resected specimens using immunohistochemistry. The association between CXCL-8/CXCR-2 expression and level of preoperative serum cytokines, C-reactive protein (CRP), coagulation factors, clinicopathologic background factors, and survival of ESCC patients was assessed. Results Thirty-seven (47%) and 36 (46%) patients were positive for CXCL-8 and CXCR-2 expression, respectively. Both CXCL-8 and CXCR-2 were expressed in 26 patients (33%). We compared the results of these 26 patients [CXCL-8(+)/CXCR-2(+) group] with those of the other group (n = 52). The depth of invasion (pT factor; P <.001), lymph node metastasis (pN factor; P =.001), pathologic stage (P <.001), lymphatic invasion (P =.010), and venous invasion (P =.001) were significantly more advanced in the CXCL-8(+)/CXCR-2(+) group compared with the other group. Preoperative IL-6, IL-8, CRP, fibrin/fibrinogen degradation product, and fibrinogen levels in the CXCL-8(+)/CXCR-2(+) group were also significantly higher than those in the other group (P =.046,.009,.029,.010, and <.001, respectively). The CXCL-8(+)/CXCR-2(+) group also showed a significantly lower recurrence-free survival (RFS; P <.001) and disease-specific survival (P =.008). As per Cox's hazards model, CXCL-8/CXCR-2 expression (hazard ratio, 2.89; P =.008) was independent predictive factor for RFS. Conclusion Increased expression of both CXCL-8 and CXCR-2 correlated with tumor progression, metastasis, higher preoperative levels of proinflammatory cytokines, CRP, activation of exogenous coagulation factors, and poor prognosis in ESCC patients. These results indicate that overexpression of both CXCL-8 and CXCR-2 may be a useful marker for predicting the outcome in ESCC patients, and more important, has potential in becoming a critical diagnostic marker for selection of appropriate treatments.

An identification of bronchial arteries (BAs) is critical in esophageal cancer surgery to avoid tracheobronchial ischemia and unexpected massive bleeding during surgical procedure particularly in thoracoscopic video-assisted esophagectomy. We describe the efficacy of three-dimensional computed tomographic angiography (3D-CTA) of BAs for preoperative evaluation in esophageal cancer surgery. Sixty-four patients with esophageal cancer who preoperatively underwent multidetector computed tomography examination were included in this study. We evaluated the number, origin, and intraoperative preservation rate of BAs, and we compared the number of thoracic paratracheal lymph nodes harvested between two groups comprising patients who either underwent preoperative 3D-CTA of BAs (3D-CTA group) or did not (non-3D-CTA group). The right and left BAs were preoperatively identified in 62 patients (97%) and 55 patients (86%), respectively, using 3D-CTA. In 34 patients (53%), the right BA originated as a common trunk with the right intercostal artery. In 48 patients (75%), the left BA originated from the descending aorta as a single or double branch. Some anomalies such as the right BA originated from the left subclavian artery were observed. In all patients, either the right or the left BA was preserved. The number of harvested lymph nodes in left side of paratrachea was significantly increased in 3D-CTA group, than those in non-3D-CTA group. 3D-CTA clearly revealed BA anatomy, contributing to BA preservation and safe and precise lymphadenectomy in esophageal cancer surgery. 3D-CTA of BAs is useful for preoperative evaluation in esophageal cancer surgery.

We report a case of chylothorax treated successfully by a new diagnostic tool: indocyanine green (ICG) fluorescence lymphography. The patient, a 65-year-old man with adenocarcinoma of the esophagogastric junction, underwent radical esophagectomy, which was followed by the development of chylothorax. On postoperative day 10, we performed transabdominal ligation of the thoracic duct. During the re-operation, we injected ICG into the mesentery of the small bowel. We then performed mass ligation of the tissue right and dorsal of the aorta, including the thoracic duct, after which a near-infrared camera system revealed a fluorescent stripe on the caudal part of the ligation. The remnant thoracic duct appeared to be dilated as a result of lymphatic stasis. The patient was discharged 35 days after his initial surgery. We report this case to demonstrate the usefulness of intraoperative ICG lymphography as a tool to identify and confirm ligation of the thoracic duct transabdominally.

Although occurring infrequently, esophagomediastinal fistula is potentially life-threatening.Wereport a rare case of intractable esophago-mediastinal fistula following thoracoabdominal aortic replacement. A 62-year-old male patient with aortic dissection underwent thoracoabdominal aortic replacement. He suddenly developed septic shock with esophageal perforation on the 6th postoperative day. Conservative therapy was employed, and he was discharged from the hospital. However, he suffered another attack of septic shock resulting from an esophago-mediastinal fistula. Gastrointestinal endoscopy revealed a suture thread beside an esophageal fistula. The patient consequently underwent esophagectomy. After removal of the esophagus, we found a suture thread with pledgets in the mediastinum and removed it. He recovered successfully thereafter. Esophago-mediastinal fistula associated with pledgets is a rare complication of thoracoabdominal aortic replacement. We believe that radical surgery can be an effective treatment. A review of the current literature did not reveal any similar cases. In this report, we discuss the clinical course of such a rare case.

Background Laparoscopy-assisted proximal gastrectomy (LAPG) remains a relatively uncommon procedure because of certain technical issues, such as curability, safety, and retention of postoperative patients' quality of life. The aim of the present study was to evaluate the feasibility of a newly developed LAPG procedure for early-stage proximal gastric cancer. Methods We enrolled 37 consecutive patients who were preoperatively diagnosed with cT1N0M0 primary gastric cancer in the upper third of the stomach with the primary tumor diameter less than 4 cm. Laparoscopy-assisted proximal gastrectomy with sentinel node (SN) mapping and esophagogastric anastomosis with a circular stapler and transoral placement of the anvil was attempted. Results The LAPG procedure was completed in 36 patients. It was converted to laparoscopy-assisted total gastrectomy in one patient because one SN detected intraoperatively was positive for metastasis by intraoperative pathological diagnosis. There were no severe postoperative complications in any patient. Only one patient (3%) complained of mild reflux symptoms immediately after operation, which were graded endoscopically as B by the Los Angeles Classification of gastroesophageal reflux disease; however, the symptoms were controlled well by a proton-pump inhibitor. Sentinel nodes were detected successfully in 37 (100%) of our patients. The mean number of dissected lymph nodes and identified SNs per case was 29.7 and 5.8, respectively. The sensitivity of prediction of nodal metastasis (including isolated tumor cells) and diagnostic accuracy based on SN status were 100% (3/3) and 100% (37/37), respectively. All patients have been free from recurrence for a median follow-up period of 26 months. Conclusions This study reveals that our novel LAPG approach is curative and represents a feasible minimally invasive surgical procedure with minimal morbidity and postoperative reflux esophagitis in patients with upper-third early-stage gastric cancer.

Proton pump inhibitors have been reported to be more useful than histamine-2 receptor antagonists for the prevention of bleeding after endoscopic submucosal dissection (ESD) for superficial gastric neoplasia. The aim of this study was to assess the effects of the proton pump inhibitor lansoprazole and the histamine-2 receptor antagonist roxatidine for the prevention of bleeding and the promotion of ulcer healing after ESD and to compare the cost-effectiveness of these two drugs. The study subjects were 129 patients who underwent ESD for superficial gastric neoplasia. The patients were randomly assigned to the lansoprazole group (L group) or the roxatidine group (R group). Either drug was administered intravenously from the morning of the ESD day to the day after the ESD, followed by oral treatment for an additional 8 weeks. A second-look endoscopy was performed on the day after the ESD, and a repeat endoscopy was performed at 8 weeks after the ESD. The incidence of bleeding and the ulcer-healing rate at 8 weeks after the ESD were analyzed, as well as the total cost of treatment with these antisecretory agents. Three patients in each group were excluded from the analysis, leaving 62 patients in L group and 61 in R group. Two of the 62 patients (3.2%) in L group and three of the 61 patients (4.9%) in R group showed bleeding after ESD ; there was no significant difference between the two groups (P = 0.68). The ulcer-healing rate was 93.5% (58/62) in L group and 93.4% (57/61) in R group (P = 1). The total cost of treatment with the antisecretory agent from the day of the ESD to day 56 after the ESD was Yen 13,212 for lansoprazole and Yen 5,841 for roxatidine. Roxatidine appears to have high cost-effectiveness in the prevention of bleeding and in the promotion of ulcer healing after ESD for superficial gastric neoplasia.

Background: It has been suggested that gastric cancer in young patients has a worse prognosis than in older patients, but this is controversial. This retrospective investigation was undertaken to understand the clinicopathological features and identify the prognostic factors of gastric cancer in young patients. Methods: Patients included in this study were those treated and followed up for gastric cancer from 1989 to 2005. Operative records, clinical, pathological, and follow-up data were reviewed. The critical age cut-off value for obtaining distinctive prognoses was 34 years. Results: Of 1730 gastric cancer patients whose records were reviewed, 27 were less than 34 years old (YGC group). The YGC group contained significantly higher percentages of females, stage IV, macroscopic type 4 tumors, poorly differentiated histology, peritoneal dissemination, and epigastric pain symptoms than the gastric cancer group aged 34 years or more (OGC group). Survival in the YGC group was significantly worse than in the OGC group (p = 0.0363). Ten-year survival was 68.5% in the YGC group and 81.8% in the OGC group. Survival in the YGC group was poorer for the stage IV patients, compared with OGC patients, especially for the stage IV patients with peritoneal dissemination and without liver metastases (H0P1 patients) (p = 0.049). Conclusions: Age in gastric cancer affects the prognosis, which in gastric cancer patients less than 34 years old was significantly poorer than for older patients, because of the high incidence of stage IV cancer with peritoneal dissemination in gastric cancer patients less than 34 years old.

Endoscopic submucosal dissection (ESD) is a novel endoscopic resection technique that enables reliable en bloc resection of large and difficult gastrointestinal lesions. We initially performed ESD using the tip of a thin-type snare to serve as a blunt-end short needle knife. However, the device had limitations; therefore, we developed a more reliable and durable device, the Flex knife. It cut well in any direction and was easy to control because of its soft and flexible nature, making it extremely useful for ESD of colorectal and esophageal lesions that required delicate maneuvering. Although the Flex knife achieved excellent treatment results, its use was still technically limited by the loop-shape tip, resulting in difficulty with knife length adjustments, frequent intraprocedure accumulation of debris on the tip, and slippage of the knife tip away from the operating field. Therefore, we designed an improved version of the Flex knife, the Dual knife. It resembles a short needle knife with a small apical disk. It has a fixed knife length: 1.5 mm for esophageal and colorectal ESD and 2 mm for gastric ESD. The small disk is useful for marking and hemostasis in a closed position and for stabilization of the knife movement against scarred or floppy tissue in an opened position, resulting in overall improved knife maneuverability and durability. In the practical Flex and Dual knife technique, sufficient submucosal injection and partial incision as well as partial submucosal dissection is key for successful ESD. Combining the endoscopist's knowledge and skill with the soft and flexible properties of the Flex and the Dual knives results in relatively safe and highly effective ESD outcomes.

Background: There is a great need for effective outpatient chemotherapy for advanced gastric cancer in patients with good performance status. The present pilot study evaluated the use of combination chemotherapy with S-1 and fractional CDDP for unresectable-recurrent gastric cancer in an outpatient setting. Patients and Methods: A total of 41 patients with unresectable or recurrent gastric cancer were treated with this combination chemotherapy. S-1 was administered orally every day on days 1-28 and CDDP was infused on days 1, 15, and 29. Results: Thirty-six patients had measurable lesions and 19 patients had partial responses, resulting in an overall response rate of 52.8%. The median survival time was 494 days. There was no grade 4 haematological toxicity, no grade 3 or more non-haematological toxicity, and no treatment-related death. Conclusion: This combination chemotherapy has no serious toxicities in patients with unresectable and recurrent gastric cancer and can be used effectively in an outpatient setting.

Advanced gastric cancer frequently RESULTS in the inability to ingest food or drink orally, a condition called malignant gastrointestinal obstruction (MGO). MGO is clinically defned as a gastrointestinal outlet obstruction caused by a large tumor, or malignant bowel obstruction with peritoneal dissemination. MGO impacts the quality of life by interfering with oral intake and by causing gastrointestinal symptoms, such as nausea, vomiting and abdominal pain. Octreotide acetate (OA) is an analogue of somatostatin which has been increasingly used to relieve gastrointestinal symptoms since it decreases the secretion of digestive juices and increases the absorption of water and electrolytes. In Japan, the oral anticancer drug S-1 was recently adopted as a key chemotherapeutic agent in advanced gastric cancer; however, its oral formulation precludes its utility in the MGO setting. This is a pilot study of chemoradiotherapy plus OA in gastric cancer with MGO. Patients were initially treated with OA to control gastrointestinal symptoms. Following resolution of their symptoms, the patients received chemotherapy with S-1 plus low-dose cisplatin and radiation. Irradiation was targeted at the primary tumor and surrounding lesions, including the lymph nodes. Grade 4 toxicity was observed in only 1 patient, and no treatment-related deaths were noted. After treatment, 3 patients achieved a partial response and 4 achieved stable disease. Of the 9 patients, 8 were able to tolerate solid food orally and were discharged. The outcomes of these cases suggest that OA is a useful adjunctive therapy that enables advanced gastric cancer patients with MGO to receive S-1-containing chemotherapy.

Normal stem cells (NSCs) are reported to exist in most tissues, including the brain, bone marrow, and probably the gastrointestinal tract. In the latter case, they are thought to possess both the self-renewal capacity and asymmetrical division capacity to generate progenitor cells which differentiate into epithelial cells. NSCs in the normal gastric mucosa are thought to be present in the proliferative zone of the neck/isthmus region, and to undergo a complex bipolar migration from the neck/isthmus region either upward or downward, becoming differentiated normal epithelial cells. NSCs in human gastric mucosa are difficult to identify due to the current lack of a useful marker. A precise definition of cancer stem cells (CSCs) is still under discussion. CSCs are generally defined as malignant cells with NSC capacity. However, many studies of CSCs have demonstrated their rapid growth and high metastatic potential, while NSCs are thought to be slow-growing and self-renewing, and to lack functional capacities such as cell migration and attachment. Recent evidence suggests the existence of CSCs in a wide variety of solid tumors. In this review, we will discuss the existence and cell biology of gastric NSCs and CSCs. We will also discuss whether gastric CSCs originate as organ-specific stem cells or as bone marrow-derived cells (BMDCs). Under certain conditions, the local microenvironment may promote the development of gastric cancer. Thus, Helicobacter pylori infection and the accompanying chronic inflammatory processes will supply critical initiators inducing cell growth and the tissue repair response, leading to carcinogenesis. This mechanism will be discussed in light of stem cell research. Progress in stem cell research in the gastric field is still limited to experimental animal models. However, recent studies should enhance our understanding of human cancer biology, and provide novel tools for the treatment of incurable gastric cancer.

Background: Salvage esophagectomy is potentially the only treatment available that can offer a chance of long-term survival when definitive chemoradiotherapy (CRT) fails to achieve local control for patients with esophageal squamous cell carcinoma (ESCC). However, salvage esophagectomy is a highly invasive procedure with various postoperative complications compared to planned esophagectomy after neoadjuvant chemoradiotherapy (CRT). We hypothesize that severe postoperative complications may affect not only surgical mortality but also tumor recurrence and long-term survival for patients with salvage esophagectomy after definitive CRT. Methods: For the present study we reviewed the surgical procedures, postoperative complications, and the prognosis of 65 consecutive patients with thoracic ESCC who underwent the esophagectomy after neoadjuvant (neoadjuvant group: n = 40) or definitive (salvage group: n = 25) CRT. Results: Most patients underwent right-transthoracic extended esophagectomy and reconstruction using gastric conduit by way of subcutaneous route with left cervical anastomosis. The incidence of postoperative pneumonia was found to be higher in the salvage group than in the neoadjuvant group. In both groups, the survival of patients with R0 resection was significantly better than those with R1/R2 resection. Moreover, in the salvage group, the postoperative survival rate of patients with pneumonia or bacteremia/sepsis was significantly lower than that for patients who did not suffer the same complications. In the neoadjuvant group, R0 resection was selected to be the only independent prognostic factor in univariate and multivariate analysis. In contrast, in the salvage group, R0 resection and bacteremia/sepsis remained significant and were independent of the other factors in multivariate analysis. Conclusions: This study reveals that postoperative morbidity affects not only the perioperative mortality but also the long-term survival of patients with ESCC who undergo salvage esophagectomy after definitive CRT.

The prognosis for advanced gastric cancer remains very poor due to the limited effectiveness of chemotherapy agents. The range in efficacy of these chemotherapy agents is likely the result of various factors including gene expression. In addition, the emergence of drug resistance during chemotherapy can result in the undesirable outcome of patients experiencing the side effects of chemotherapy without benefiting in terms of tumor response. Gene expression profiling provides a unique opportunity to gain insight into the development of different types of gastric cancer. We applied the TaqMan low density array to investigate the expression of 96 genes in four gastric cancer cell lines (TMK-1, MKN-45, MKN-74 and CDDP-resistant MKN-74). The cell lines displayed different patterns of gene expression alteration after exposure to the chemotherapeutic drugs cisplatin and 5-fluorouracil. We also established that cisplatin-resistant MKN-74 cells do not show the same gene expression patterns as the parental MKN-74 cell line at 0, 8 and 24 h after CDDP exposure. This study reveals the underlying complexity of biological and pathological events and could, perhaps, contribute to new experimental protocols or treatments that would achieve a consistent and desirable outcome of chemotherapy.

A 68-year-old woman presented with severe bowel obstruction and was subsequently diagnosed with stage IV gastric cancer with peritoneal dissemination. She was immediately stabilized in the hospital with the placement of a nasointestinal tube. Abdominal computed tomography showed multiple intraperitoneal nodules consistent with peritoneal dissemination of the gastric cancer. The patient's inability to tolerate oral intake was a contraindication to using S-1 chemotherapy, currently one of the most effective medications used for gastric cancer in Japan. Therefore, she was initially treated with octreotide acetate (OA). Her bowel obstruction was sufficiently attenuated on the seventh day after the initiation of treatment with OA to permit the initiation of oral S-1, along with low-dose cisplatin (CDDP) and radiation. S-1 was orally administered at a dose of 100 mg/day per body (80 mg/m2 per day) on days 1-28, and CDDP was infused at a dose of 7.8 mg/day per body (6 mg/m2 per day) on days 1-5, 8-12, and 15-19. Radiation therapy (2 Gy/day for 5 days/week) was performed with the chemotherapy. Despite no change being shown on her imaging findings with the chemotherapy, the patient's bowel obstruction resolved and she was able to tolerate both liquids and solid food orally. She was discharged 2 months after admission. Seven months after beginning the chemotherapy, she was still doing well on outpatient chemotherapy with S-1 and CDDP, and had no decline in her quality of life or progression of her disease.

A 68-year-old male was diagnosed as type 2 gastric cancer in the upper part of the stomach, then diagnosed as cT2 (MP) N0M0H0P0, cStage I B. Total gastrectomy and splenectomy with D2 lymph node dissection were performed. Final diagnosis including pathology was pT1 (SM) N1M0H0P0, pStage IB, and with his informed consent, an anti-cancer drug, UFT, was given as postoperative adjuvant therapy. Four months after the surgery, a 35-mm sized tumor recurring around the distal region of pancreas was detected by abdominal computed tomography (ACT). Then, combination chemo-radiotherapy using S-1, cisplatin and radiation (50 Gy) was performed. One year after the initial surgery, ACT showed a complete response (CR) of the recurred tumor, while outpatient chemotherapy with S-1+CPT-11 and S-1+paclitaxel was continuously performed, because of elevated CEA. Two years after initial surgery, the CEA value was elevated to 28.4 ng/mL, and so S-1 +docetaxel was applied. The patient is still alive with no sign of lesion recurrence by CT 3 years after initial surgery. Outpatient chemotherapy helped the patient maintain good quality of life. In addition, initial therapy for the recurred tumor including radiation proved to be a powerful way to control local growth of gastric cancer, even if hematogenous/lymphatic spreading of gastric cancer cells might be difficult to suppress with such chemo-radiotherapy.

The development of a specific antibody for cancer therapy could enable a potent strategy for overcoming cancer. As ideal immunotherapy, a human monoclonal antibody (HuMoAb) might have a useful antitumor effect without any lethal toxicities. Thirty-six unique clones producing HuMoAbs were successfully developed using tumor infiltrating lymphocytes collected from 28 patients with several malignant solid tumors. The 36 tumor-specific immunoglobins were found among 9,450 clones after 43 fusions by the conventional hybridoma method. Among these 36 HuMoAbs, 9 had a remarkable tumor-specific reaction and no reaction with normal tissues, as determined with quantum dots-streptavidin and a fluorescence microscope. The inhibition of cell proliferation by the HuMoAbs was evaluated with the MTT assay. Over 40% cell growth inhibition was confirmed with 4 of the 36 HuMoAbs. Two of the antibodies had highly-specific reactivity to carcinomatous lesions with strong growth inhibition and up to 94.3% inhibition of the control growth. In conclusion, 36 clones with HuMoAbs that have specific reactions with cancer cells were successfully established. These HuMoAbs might be utilized as either anticancer or drug delivery agents.

Purpose: The results of a pilot study using S-1/low-dose cisplatin/radiotherapy led us to hypothesize that the initial chemoradiotherapy regimen would induce a 70% efficacy rate with a 10% pathologic complete response rate. Patients and Methods: Only patients with unresectable or incurable advanced gastric cancer were eligible. The patients received induction S-1 and cisplatin therapy with radiotherapy followed by chemotherapy alone. Results: Of the 30 patients recruited and assessed, 29 were eligible for clinical evaluation of measurable lesions. The response rate was 65.5%, with 19 with a partial response, 8 with no change, and 2 with progressive disease of 29 patients. Of the 30 patients recruited, 10 (33.3%) underwent stomach resection and D2 LN dissections. The pathologic complete response rate was 13.3% (4 patients), and the R0 resection rate was 100% (10 patients). The survival analysis showed a median survival time of 25 months. Grade 3 toxicity occurred in 66.7% for leukocytopenia, 33.3% for thrombocytopenia, 23.3% for nausea and appetite loss, and 6.7% for anemia, diarrhea, and renal dysfunction. Although all the patients had been hospitalized with a poor performance status with a giant tumor, 97% (29 of 30) could be discharged after the first cycle, resulting in an improvement in quality of life. Conclusion: Chemoradiotherapy could be a powerful regimen for controlling tumor progression in advanced gastric cancer, improving patients' quality of life with tolerable toxicity. A complete histologic response rate of >10% would be expected, even for large tumors with metastatic lesions.

We have performed chemoradiation with S-1 and low-dose CDDP as an initial treatment for 27 patients with incurable or unresectable highly advanced gastric cancer since 2002. Twelve out of 27 patients received combination chemotherapy of S-1 and CPT-11 as the second-line chemotherapy. On this regimen, S-1 was administered orally at a dose of 80 mg-120 mg daily, and CPT-11 at a dose of 60 mg/m(2) once in 2 or 3 weeks for outpatients. Clinical effects after therapy showed a response rate of 30.0%. Considering the prognostic outcome of the regimen, the one-year survival rate of the therapy was 66.7%, and the median survival time was more than 1 year, suggesting second-line chemotherapy will be one of the beneficial regimens in gastric cancer patients. Although 4 patients showed grade 3 bone marrow suppression (33.3%), they were all able to continue the therapy, after recovering from toxicity by means of G-CSF and/ or cessation of chemotherapy. The incidence and level of toxicity accompanying subjective symptoms, however, were relatively low, and the regimen was useful as an outpatient treatment maintaining good quality of life and improving their prognosis. Treatment with an appropriate regimen at an appropriate time will enable these patients to have good quality of life and survival.

Recent development and clinical application of novel anticancer agents like S-1 have been reported to show a good outcome against gastric cancer (GC) with peritoneal dissemination (P). In our study, a retrospective analysis of the treatment for GC with P was performed. Since 1989, a chemosensitivity test with MTT assay (MTTA) using surgical specimen was performed to choose chemotherapy after surgery, resulting in good prognosis in patients who received drugs which were determined effective by the MTTA. Since 1999, S-1 was introduced as adjuvant chemotherapy, and, since 2002, initial treatment with S-1/CDDP was used for GC with P, suggesting a better prognostic outcome compared with previous results with ineffective chemotherapy or surgery alone. In conclusion, prognosis of GC with P has been improving by effective regimens with novel anticancer agents like S-1. Further research and clinical trials will be necessary to achieve a more satisfactory outcome with the treatment of GC with P.

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