A case of lymph node metastasis following a curative endoscopic submucosal dissection of an early gastric cancer.

Currently in Japan, differentiated gastric submucosal invasive cancers <500 µm (SM1) with negative lymphovascular involvement are included in expanded pathological criteria for curative endoscopic treatment. This is based on a retrospective examination of surgical resection cases in which patients suitable for such expanded criteria were determined to have a negligible risk of lymph node metastasis. We performed endoscopic submucosal dissection on a 65-year-old male with early gastric cancer in April 2005, and pathology revealed a well-differentiated adenocarcinoma, 21 × 10 mm in size, SM1 invasion depth and negative lymphovascular invasion as well as tumor-free margins, so the case was diagnosed as a curative resection. This case, however, resulted in lymph node metastasis that was diagnosed by endoscopic ultrasonography with fine-needle aspiration biopsy in May 2009. Distal gastrectomy with D2 lymph node dissection was then performed, confirming lymph node metastasis from the original gastric cancer.

Identification of risk factors for esophagojejunal anastomotic leakage after gastric surgery.

BACKGROUND: Despite the development of the surgical technique and improvements in perioperative management, anastomotic leakage still occurs at esophagojejunal anastomoses after total or proximal gastrectomy. Anastomotic leakage is one of the major complications of concern, chiefly because it can lead to death. The objective of the present study was to identify the risk factors for esophagojejunal anastomotic leakage. METHODS: The study was based on retrospective analysis of the data of a total of 1,640 consecutive patients who underwent total, proximal, or completion gastrectomy, including esophagojejunal anastomosis, between 1999 and 2008. RESULTS: Thirty-five patients (2.1 %) developed anastomotic leakage. Univariate analysis revealed patient age, pulmonary insufficiency, lymph node dissection, combined resection of other organs, omental resection, operative time, blood loss, intraoperative blood transfusion, and postoperative creatinine level were the significant factors influencing anastomotic leakage. Multivariate analysis identified pulmonary insufficiency and the duration of the operation as the predictors of anastomotic leakage. CONCLUSIONS: To avoid leakage, surgeons should take care in creating the anastomosis in gastrectomy patients, particularly in cases of poor pulmonary function or when the procedure requires a longer operation.

Optimal extent of lymph node dissection for Siewert type II esophagogastric junction carcinoma.

OBJECTIVE: To determine the optimal extent of lymph node dissection for carcinomas of the true cardia, otherwise called Siewert type II esophagogastric junction (EGJ) carcinomas. BACKGROUND: In patients with cancer of the EGJ, comparable outcomes have been obtained with extended esophagectomy and total gastrectomy. The issue of the optimal surgical approach for EGJ tumors has been under debate. Nodal involvement is a strong predictor of survival, however, the optimal extent of prophylactic lymphadenectomy for Siewert type II tumors remains to be elucidated. METHODS: We retrospectively evaluated the distributions of the metastatic nodes, the recurrence pattern, and the oncological outcomes in a single-center large cohort of 225 patients with Siewert type II tumors. To assess the therapeutic outcomes of respective node dissection, we applied an index calculated by multiplication of the incidence of metastasis by the 5-year survival rate of patients with metastasis in the respective node stations. RESULTS: The incidence of nodal metastasis was high in the right paracardial (38.2%), lesser curve (35.1%) and left paracardial (23.1%) nodes, and also the nodes along the left gastric artery (20.9%). Involvement of the suprapancreatic nodes along the celiac artery, splenic artery and common hepatic artery was found in 23, 25, and 14 patients, respectively. According to the index of estimated benefit from lymph node dissection, dissection of the paracardial and lesser curve nodes yielded the highest therapeutic benefit. The number of metastatic nodes in these areas was as predictive of the disease-free and overall survivals as the TNM pN category. The 5-year overall survival rates in patients with no or 1-2 metastatic nodes were 76.6% and 62.3%, respectively, whereas the 5-year survival rate in those with 3 or more positive nodes was only 22.4%, comparable with the rate of 17.4% in patients with TNM pN3 tumors. CONCLUSIONS: Clear anatomic distinction of EGJ tumors is likely to provide insight into the appropriate extent of lymphadenectomy. Dissection of the paracardial and lesser curve nodes is essential for staging as well as for obtaining therapeutic benefit in surgery for in EGJ carcinomas (Siewert type II).

Management of adjuvant S-1 therapy after curative resection of gastric cancer: dose reduction and treatment schedule modification.

BACKGROUND: The aim of this study was to determine the optimal management of adjuvant S-1 therapy for stage II or III gastric cancer, encompassing the details of dose reduction and treatment schedule modification. METHODS: We retrospectively examined 97 patients with stage II or III gastric cancer who received S-1 chemotherapy following gastrectomy between January 2003 and December 2007. S-1 (80 mg/m² per day) was orally administered twice daily for 4 weeks, followed by a 2-week rest. As a rule, treatment was continued for 1 year after gastrectomy. Dose reduction or treatment schedule modification was performed according to toxicity profiles. RESULTS: Among the 97 patients, 57 (59%) underwent dose reduction at least once and 39 (40%) received treatment schedule modification. Of the 57 patients who required dose reduction, 45 (79%) underwent reduction within 3 months of the beginning of treatment. The most common reasons for dose reduction were anorexia (47%), followed by diarrhea (32%), leukopenia (24%), and rash (16%), with the reasons overlapping. Although the difference in the requirement for dose reduction was not significant, patients with a low creatinine clearance level or those who underwent total gastrectomy had a greater tendency to require dose reduction. The duration of the S-1 treatment period was at least 3 months in 88% of the patients, at least 6 months in 82%, and the planned 1-year period in 73% of the patients. CONCLUSIONS: In most patients, the planned 1-year adjuvant S-1 therapy for stage II or III gastric cancer could be completed by modifying the dose reduction and treatment schedule.

Present and future status of gastric cancer surgery.

The type of surgery and the role of adjuvant therapies in the treatment of gastric cancer have changed in recent times. The treatment of gastric cancer with curative intent is moving away from standard D2 or more extensive surgery to a tailored approach depending on the stage of the disease. Data collected from extensive lymphadenectomy for all stages of gastric cancer have confirmed that some subsets of early gastric cancer are very low risk for nodal metastasis. This group of patients may benefit from resection by endoscopic or laparoscopic techniques and may also be suitable for function-preserving procedures. The extent of resection for gastric cancer has always excited debate. D2 gastrectomy was criticized for its higher mortality in the early European Phase III trials, but recent studies from Taiwan and Italy have shown that the procedure is safe when performed by experienced surgeons and has a survival benefit over D1 gastrectomy. The role of para-aortic lymph node dissection for nodes without apparent metastasis in advanced gastric cancer was assessed by a Phase III Japanese trial and showed no additional benefit over D2 resection. Radical gastric resections, involving resection of adjacent organs for direct tumor invasion result in higher rates of complications, and the role of multi-visceral resections has also been reevaluated. Effective adjuvant therapies for gastric cancer have been reported since the early part of 2000. Development of more effective adjuvant therapy combined with D2 resection should continue to improve survival in the future.

Laparoscopy-assisted pylorus-preserving gastrectomy: a matched case-control study.

BACKGROUND: Pylorus-preserving gastrectomy (PPG) has been widely accepted as the standard treatment for early gastric cancer, and the laparoscopic approach has been gradually introduced. The aim of this study is to investigate the short-term outcome of laparoscopy-assisted PPG (LAPPG) in comparison with open PPG (OPPG). METHODS: Between April 2006 and May 2009, a cohort of 418 patients with early gastric cancer in the middle third of the stomach underwent PPG, and 90 of the LAPPG patients and 90 of the OPPG patients among them were matched for sex, age, and body mass index. The outcomes of the patients in the two groups were then compared. RESULTS: Operation time was significantly longer in the LAPPG group than in the OPPG group (270 vs. 195 min, P < 0.001), and there was significantly less blood loss in the LAPPG group than in the OPPG group (29 vs. 97 ml, P < 0.001). The overall incidence of surgery-related complications in the two groups was similar (8.9 vs. 11.1%). The proportion of patients who used analgesics after postoperative day 5 was significantly lower in the LAPPG group than in the OPPG group (35.6 vs. 61.1%, P = 0.001). There was no significant difference between the two groups in the interval between surgery and resumption of oral feeding, the interval between surgery and first flatus, number of patients with body temperature of 38°C or more, or length of hospital stay. CONCLUSIONS: LAPPG can be performed safely in terms of short-term outcome.

PON1 Q192R is associated with high platelet reactivity with clopidogrel in patients undergoing elective neurointervention: A prospective single-center cohort study.

BACKGROUND AND PURPOSE: The impact of the paraoxonase-1 (PON1) polymorphism, Q192R, on platelet inhibition in response to clopidogrel remains controversial. We aimed to investigate the association between carrier status of PON1 Q192R and high platelet reactivity (HPR) with clopidogrel in patients undergoing elective neurointervention. METHODS: Post-clopidogrel platelet reactivity was measured using a VerifyNow® P2Y12 assay in P2Y12 reaction units (PRU) for consecutive patients before the treatment. Genotype testing was performed for PON1 Q192R and CYP2C19*2 and *3 (no function alleles), and *17. PRU was corrected on the basis of hematocrit. We investigated associations between factors including carrying ≥1 PON1 192R allele and HPR defined as original and corrected PRU ≥208. RESULTS: Of 475 patients (232 men, median age, 68 years), HPR by original and corrected PRU was observed in 259 and 199 patients (54.5% and 41.9%), respectively. Carriers of ≥1 PON1 192R allele more frequently had HPR by original and corrected PRU compared with non-carriers (91.5% vs 85.2%, P = 0.031 and 92.5% vs 85.9%, P = 0.026, respectively). In multivariate analyses, carrying ≥1 PON1 192R allele was associated with HPR by original (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.03-3.76) and corrected PRU (OR 2.34, 95% CI 1.21-4.74) after adjustment for age, sex, treatment with antihypertensive medications, hematocrit, platelet count, total cholesterol, and carrying ≥1 CYP2C19 no function allele. CONCLUSIONS: Carrying ≥1 PON1 192R allele is associated with HPR by original and corrected PRU with clopidogrel in patients undergoing elective neurointervention, although alternative results related to other genetic polymorphisms cannot be excluded.

Incidence of pulmonary thromboembolism in gastric cancer surgery using routine thromboprophylaxis.

BACKGROUND: There is a lack of published data on the incidence of pulmonary thromboembolism (PTE) after resections for gastric cancer. We report the incidence of PTE after gastric cancer surgery with routine thromboprophylaxis from a high-volume center. METHODS: Between October 2002 and December 2008, 3262 patients underwent gastric cancer surgery with routine thromboprophylaxis using low-dose unfractionated heparin, intermittent pneumatic compression, fluid infusion, and graduated compression stockings. Patients diagnosed with PTE were identified from a prospectively collected database that included complications related to thromboprophylaxis. RESULTS: Seven patients (0.2%) developed symptomatic PTE in this series. Multivariate analysis demonstrated that female sex (P = 0.029) and high body mass index (P = 0.025) were significant risk factors for PTE. The most common symptom was dyspnea (57%). Five patients (71%) developed PTE by the second postoperative day. All patients were treated successfully with medical treatment and no hospital deaths were recorded. Adverse events related to thromboprophylaxis included major postoperative bleeding in 10 (0.3%) of the 3262 patients. There were no cases of hematoma related to the insertion of epidural catheters for analgesia. CONCLUSION: The routine use of thromboprophylaxis in Japanese patients undergoing gastric resection is safe and effective in reducing the incidence of pulmonary thromboembolism.

Trends in characteristics of surgically treated early gastric cancer patients after the introduction of gastric cancer treatment guidelines in Japan.

BACKGROUND: The gastric cancer treatment guidelines (Guidelines) of the Japanese Gastric Cancer Association allow endoscopic treatment and a modified gastrectomy for the treatment of early gastric cancer (EGC). Endoscopic treatment is indicated for EGC with a minimal chance of nodal metastasis. Consequently, surgeons will likely treat an increasing number of EGC patients with greater chance of nodal metastasis using a reduced extent of lymphadenectomy. The aim of this study was to investigate the trends in characteristics and long-term oncological outcomes of surgically treated EGC patients after the introduction of the Guidelines. METHODS: Between 2001 and 2003, 696 patients underwent a gastrectomy according to the Guidelines. These 696 patients (the Guidelines group) were retrospectively compared with 635 patients (the control group) who had undergone a gastrectomy between 1991 and 1995 (before the introduction of the Guidelines). RESULTS: The incidence of nodal metastasis in mucosal cancers was higher in the Guidelines group than in the control group (6.5% vs 2.6%). The proportion of D2 or greater extended lymphadenectomy in the Guidelines group was lower than that in the control group (29.7% vs 62.5%). Nevertheless, the 5-year survival rate in the Guidelines group was similar to that in the control group (94.2% vs 92.3%). CONCLUSION: Surgeons treated more cases of mucosal cancer with nodal metastasis after the introduction of the Guidelines. The long-term oncological outcomes for patients with EGC remained excellent. So far, the Guidelines for the treatment of EGC appear acceptable.

Correlation between the length of the pyloric cuff and postoperative evaluation after pylorus-preserving gastrectomy.

BACKGROUND: Recent years have seen the preserved pyloric cuff being lengthened in pylorus-preserving gastrectomy for early gastric cancer. We performed clinical assessment of the symptoms after pylorus-preserving gastrectomy in patients treated at the National Cancer Center Hospital in Japan during the past 9 years. METHODS: Four hundred and fifty-six patients who had undergone pylorus-preserving gastrectomy and been followed up for at least 3 years were studied. We classified the patients into two groups according to the length of the pyloric cuff (group A, within 3.0 cm; group B, more than 3.0 cm). Medical records were reviewed for further histological and follow-up data. A questionnaire regarding dumping syndrome and gastric stasis was also completed by the patients. RESULTS: Our results showed no statistically significant differences in symptoms, such as dumping syndrome or emptying disturbances, between the two groups. CONCLUSION: Our study revealed that the differences in several functions and symptom scales were not pronounced between the two groups. Regardless of the length of the pyloric cuff, pylorus-preserving gastrectomy can be utilized for the treatment of early gastric cancer even if the tumor is located proximal to the middle body.

Safety and feasibility of laparoscopy-assisted distal gastrectomy with suprapancreatic nodal dissection for clinical stage I gastric cancer: a multicenter phase II trial (JCOG 0703).

BACKGROUND: Although the number of patients undergoing laparoscopy-assisted distal gastrectomy (LADG) has been increasing, a prospective study with a sample size sufficient to investigate the benefit of LADG has never been reported. We conducted a multi-institutional phase II trial to evaluate the safety of LADG with nodal dissection for clinical stage I gastric cancer patients. METHODS: The subjects comprised patients with clinical stage I gastric cancer who were able to undergo a distal gastrectomy. LADG with D1 plus suprapancreatic node dissection was performed. The primary endpoint was the proportion of patients who developed either anastomotic leakage or a pancreatic fistula. The secondary endpoints included surgical morbidity and short-term clinical outcome. RESULTS: Between November 2007 and September 2008, 176 eligible patients were enrolled. The proportion of patients who developed anastomotic leakage or a pancreatic fistula was 1.7%. The overall proportion of in-hospital grade 3 or 4 adverse events was 5.1%. The short-term clinical outcomes were as follows: 43.2% of the patients requested an analgesic on postoperative days 5-10; the median time from surgery until the first episode of flatus was 2 days; and 88 patients (50.0%) had a body temperature of 38 °C or higher during their hospital stay. CONCLUSIONS: This trial confirmed the safety of LADG performed by credentialed surgeons in terms of the incidence of anastomotic leakage or pancreatic fistula formation. A phase III trial (JCOG 0912) to confirm the noninferiority of LADG to an open gastrectomy in terms of overall survival is ongoing.

Afferent loop obstruction after distal gastrectomy with Roux-en-Y reconstruction.

BACKGROUND: The incidence of afferent loop obstruction after gastrectomy with Roux-en-Y reconstruction has not yet been reported. The aim of this study was to elucidate the incidence of afferent loop obstruction after distal gastrectomy with Roux-en-Y reconstruction performed through an open approach. METHODS: We conducted a retrospective review of the data of 1908 patients who underwent distal gastrectomy followed by Roux-en-Y reconstruction through an open approach between January 1999 and December 2008. RESULTS: Four patients (0.2%) developed afferent loop obstruction. The median age of the patients, consisting of three men and one woman, was 64 years (range 46-78 years). The cause of the afferent loop obstruction was internal herniation in two patients, adhesion in one patient, and peritoneal recurrence in one patient. The internal herniation occurred at the mesenteric gap in the region of the jejunojejunostomy. The interval between the initial gastrectomies and the emergency operations for afferent loop obstruction ranged from 3 weeks to 2 years (median 5 months). Three of the four patients were symptomatic, with vomiting and abdominal pain. All patients recovered following the emergency operations, and none died of this complication. CONCLUSIONS: Afferent loop obstruction develops rarely after distal gastrectomy with Roux-en-Y reconstruction through an open approach. This rare but fatal complication should be considered when a patient complains of abdominal pain and/or vomiting after distal gastrectomy with Roux-en-Y reconstruction.

Stenosis of esophago-jejuno anastomosis after gastric surgery.

BACKGROUND: Stenosis of esophago-jejuno anastomosis is one of the postoperative complications of gastric surgery. This complication usually manifests with the symptom of dysphagia and is treated by endoscopic dilatation. No large-scale studies have been conducted to determine the incidence of this complication after surgery. METHODS: The data of a total of 1478 consecutive patients who underwent total, proximal, or completion gastrectomy, including esophago-jejuno anastomosis, between 2000 and 2008 were analyzed retrospectively with a view to determining the incidence of anastomotic stenosis. RESULTS: Sixty patients (4.1%) developed stenosis of the esophago-jejuno anastomosis which needed to be treated by endoscopic balloon dilatation. The average interval between the surgery and detection of stenosis was 67.4 days (median = 58.0). Multivariate analysis identified female gender, proximal gastrectomy, use of a narrow-sized stapler, and the choice of the stapling device as significant factors influencing the risk of development of anastomotic stenosis. CONCLUSION: Esophago-jejuno anastomotic stenosis appears to be a common late postoperative complication after gastric surgery. Endoscopic examination and treatment yielded favorable outcomes in patients complaining of dysphagia after gastric surgery.

Significance of lavage cytology in advanced gastric cancer patients.

BACKGROUND: Lavage cytology positive (Cy1) is well known as a poor prognostic factor in advanced gastric cancer patients. However, the optimal therapeutic strategy for patients with Cy1 has not yet been established. The aim of this study was to evaluate the clinical significance of Cy1 for the purpose of establishing a suitable therapeutic strategy. METHODS: The data of 996 consecutive advanced gastric cancer patients who underwent gastrectomy between 1992 and 1998 at the National Cancer Center Hospital were retrospectively studied. RESULTS: The 2- and 5-year survival rates of the patients who underwent gastrectomy without any other noncurative factors besides Cy1 were 25.3 and 7.8%, respectively. When the analysis was limited to type 4 advanced gastric cancer patients, none of the patients with Cy1 survived for more than 40 months. CONCLUSIONS: The prognosis of gastric cancer patients with Cy1 is very poor. Some patients show long survival after standard gastrectomy with D2 lymph node dissection; however, the prognosis of type 4 gastric cancer patients with Cy1 is so poor that multimodality therapy, including perioperative chemotherapy, is essential.

Identification of prognostic biomarkers in gastric cancer using endoscopic biopsy samples.

Endoscopic biopsy prior to chemotherapy provides an opportunity for studying biomarkers to predict the overall survival in gastric cancer patients. This prospective study was performed to identify prognostic biomarkers in patients with unresected gastric cancer. Fifty-nine cases of chemotherapy-naive metastatic gastric cancer were enrolled in this study. A microarray analysis was performed using 40 biopsy samples to identify candidate genes whose expressions might be correlated with the overall survival. After adjusting for clinical covariates based on a multivariate analysis, the identified genes were validated using real-time reverse transcription polymerase chain reaction (RT-PCR) analysis in 19 independent validation samples. Ninety-eight candidate genes whose expression levels were significantly correlated with the overall survival were identified using a microarray analysis based on a proportional hazards model (P < 0.005). Multivariate analysis was performed to assess 10 of these genes, and the results yielded a statistical significance level for DACH1 and PDCD6. We further evaluated these two genes in independent samples using real-time RT-PCR and found that lower mRNA expression levels of PDCD6 were correlated significantly with a poor overall survival. We identified PDCD6 as a prognostic biomarker in patients with unresected gastric cancer using endoscopic biopsy samples. Our PCR-based single gene prediction strategy successfully predicted the overall survival and may lead to a better understanding of this disease subgroup.

[Reconstruction after distal gastrectomy].

To select the best reconstruction method after distal gastrectomy, we analyzed the endoscopic features and gastrointestinal quality of life in patients who underwent either Billroth I or Roux-en-Y reconstruction. The Billroth I procedure is simpler, more physiologically normal, and allows easier endoscopic access to the duodenum. Although it is more complex, the Roux-en Y procedure can prevent bile reflux, is safe, and is superior to the Billroth I procedure both functionally and symptomatically. The Roux-en-Y procedure is thus one of the best options after distal gastrectomy. Selection of the reconstruction procedure should be based on clinical evidence.

Dural and Pial Arteriovenous Fistulas Connected to the Same Drainer in the Middle Cranial Fossa: A Case Report.

BACKGROUND: Dural arteriovenous fistulas (AVFs) in the middle cranial fossa are rare. Pial AVFs are similarly rare but differ from dural AVFs in that they derive their arterial supply from pial or cortical arterial vessels and do not lie within the intradural region. We report an extremely rare case of dural and pial AVF connected to the same drainer in the middle cranial fossa. CASE DESCRIPTION: In a 58-year-old man with a subcortical hemorrhage in the right temporal lobe, digital subtraction angiography showed a dural AVF in the middle cranial fossa fed by the middle meningeal artery (MMA) and draining into the sphenopetrosal vein. A combination with a small pial AVF connected to the same sphenopetrosal vein was suspected. Open surgery was performed to directly observe the shunt points. Transarterial indocyanine green (ICG) angiography using the MMA via the superficial temporal artery on a skin flap was performed to repeatedly and distinctly evaluate the dural shunt points and to prevent cerebral thromboembolism. Although the dural supply was completely disconnected, the sphenopetrosal vein remained arterialized. ICG angiography revealed pial AVF, which was fed by the cortical arteries draining into the same drainer. The pial supply was completely disconnected, and disappearance of the dural and pial AVF was confirmed. CONCLUSIONS: We report an extremely rare case of dural and pial AVF connected to the same drainer in the middle cranial fossa. To our knowledge, this is the first such case report described in the literature.

[Informed consent for gastric cancer surgery].

Gastric cancer patients must have sufficient information on their prognosis and the risks and benefits associated with different therapeutic options before giving informed consent for treatment. The clinical stage of the cancer should be explained, along with the possibility of stage migration after surgery. The procedure proposed should be compared with other therapies including best supportive care, with explanations of postoperative prognosis, actual morbidity and mortality rates at the individual institution, and aftereffects. The surgeon should also explain measures to prevent and treat aftereffects, including dietary restrictions, reflux, dumping syndrome, and adhesive bowel obstruction. Because some patients refuse blood transfusions on religious grounds, the consent to undergo transfusion should be obtained separately from that to undergo surgery. Resected tissue is considered to be personal information, and consent must be obtained for its use in subsequent research after histopathologic examination. Adjuvant chemotherapy using S-1 is a standard treatment option in advanced gastric cancer of stage II or III, for which patients should make an informed choice after sufficient explanations of its efficacy and adverse effects.

Improving treatment times for patients with in-hospital stroke using a standardized protocol.

BACKGROUND: Previous reports have shown significant delays in treatment of in-hospital stroke (IHS). We developed and implemented our IHS alert protocol in April 2014. We aimed to determine the influence of implementation of our IHS alert protocol. METHODS: Our implementation processes comprise the following four main steps: IHS protocol development, workshops for hospital staff to learn about the protocol, preparation of standardized IHS treatment kits, and obtaining feedback in a monthly hospital staff conference. We retrospectively compared protocol metrics and clinical outcomes of patients with IHS treated with intravenous thrombolysis and/or endovascular therapy between before (January 2008-March 2014) and after implementation (April 2014-December 2016). RESULTS: Fifty-five patients were included (pre, 25; post, 30). After the implementation, significant reductions occurred in the median time from stroke recognition to evaluation by a neurologist (30 vs. 13.5min, p<0.01) and to first neuroimaging (50 vs. 26.5min, p<0.01) and in the median time from first neuroimaging to intravenous thrombolysis (45 vs. 16min, p=0.02). The median time from first neuroimaging to endovascular therapy had a tendency to decrease (75 vs. 53min, p=0.08). There were no differences in the favorable outcomes (modified Rankin scale score of 0-2) at discharge or the incidence of symptomatic intracranial hemorrhage between the two periods. CONCLUSION: Our IHS alert protocol implementation saved time in treating patients with IHS without compromising safety.

[Adjuvant chemotherapy using S-1 for curatively resected gastric cancer-the nationwide clinical trial].

Actually there has been no established adjuvant therapy for curable gastric cancer. Thus it is strongly recommended in the guidelines to actively carry out clinical trials. A large scale clinical trial on adjuvant chemotherapy for gastric cancer using S-1 (ACTS-GC) started in 2001. This was the first large trial having the surgery alone as control after 1980. The target population was Stage II, IIIA, IIIB, and the expected hazard ratio was less than 0.70. Between October 2001 and December 2004, for 3 years and 2 months, 1,056 patients were enrolled. Thus it was proven that we should carry out a pivotal study instead of making meta-analysis in the field of gastric cancer. Certainly, the results of this trial will strongly affect the clinical practice in Japan. If the results are negative, the use of adjuvant chemotherapy in practice and in social insurance might be restricted.