Gastric Cancer Patients In Japan Research Articles

Development of an artificial intelligence algorithm for adjuvant chemotherapy based on a nationwide registry of patients with gastric cancer by the Japanese Gastric Cancer Association (JGCA).

4063 Background: Recent marked advances in machine learning have led to expectations of the clinical application of artificial intelligence (AI) to support medical care. Methods: A survival analysis model which consisted of 31 covariates was adopted for AI algorithms using machine learning and these were constructed using clinical data sets for training. The performance of AI algorithms was evaluated in order to determine the optimal chemotherapy including surgery alone without any adjuvant chemotherapy with the highest survival rate for each patient. This involved using clinical data for verification to compare survival of an AI-recommended treatment group, for which therapy recommended by AI was actually administered, with an AI-deprecated group, for which therapy recommended by AI was not administered. Results: The clinical characteristics of 23653 patients and treatment are described in the Table from 2011 to 2018 in a nationwide registry of gastric cancer patients in Japan by the Japanese Gastric Cancer Association and were made available for this study. S-1 monotherapy was used the most frequently of all adjuvant chemotherapy in this study. We used the "restricted mean overall survival time" (RMST) of all the patients as metrics. The RMST in the AI-recommended and the AI-deprecated groups were 51.4 and 47.5 months, respectively. Patient data for the verification were matched baseline characteristics by the propensity score. This model predicted effectively overall survival after gastrectomy. The RMST of over 80 years old patients were 43.9 in the AI-recommended and 38.3 months in the AI-deprecated, respectively. This AI algorithm recommended adjuvant S-1 more frequently for patients with higher age, male, American Society of Anesthesiologists – physical status 2, Eastern Cooperative Oncology Group performance status 1, pT3/pT4, pN2/pN3, more than the upper normal limit of preoperative blood urea nitrogen, macroscopic types 2/3, differentiated adenocarcinoma, Roux-en-Y reconstruction, and Clavien-Dindo classification grade II/III. The RMST for pStage IIA/IIB/IIIA/IIIB/IIIC were 55.7/53.9/50.3/45.7/42.2 months in the AI-recommended and 55.1/50.7/43.9/36.9/32.0 months in the deprecated. This AI algorithm showed a higher survival rate in pStage III patients particularly. Conclusions: The AI algorithm could readily be integrated into clinical practice to choose adequate adjuvant chemotherapy for each patient based on each patient's baseline data because it trained and verified the nationwide registry has good predictive performance. [Table: see text]

PMD9 Cost-Minimization Analysis of Robotic-Assisted Surgery for Gastric Cancer Patients in JAPAN

The Robotic assisted surgical procedure had only been reimbursed for prostate / renal cancer patients under Japanese health insurance system. In 2018 it was expanded to twelve other disease areas, while no premium is given for extended area. Gastrectomy is thought to be important procedure among 12 ones in East Asia, as gastric cancer is more prevalent than that in Europe / the US. Our objective is to compare average length of stay (ALOS) and medical expenses among different surgery methods, or robotic-assisted, conventional, and open gastrectomy.

Predicting EQ-5D Utility Index Scores for Gastric Cancer Patients in Japan: A Preliminary Model

Predicting EQ-5D Utility Index Scores for Gastric Cancer Patients in Japan: A Preliminary Model

Evaluation of postgastrectomy symptoms after distal gastrectomy with Billroth-I reconstruction using the Postgastrectomy Syndrome Assessment Scale-45 (PGSAS-45).

Distal gastrectomy with Billroth-I reconstruction (DGBI) is the most commonly used treatment approach for gastric cancer patients in Japan. The aim of this study was to assess and elucidate the effect of different surgical DGBI techniques on postgastrectomy syndrome (PGS) using the Postgastrectomy Syndrome Assessment Scale-45 (PGSAS-45). The newly created PGSAS-45 composed of 45 questions was used in this study. The scale was distributed to 2,922 patients who underwent gastrectomy >1year prior. Completed forms were returned by 2,520 patients (86%), of which 909 underwent DGBI. The effects of performing the Kocher maneuver, differences in the size of the gastric remnant and differences the anastomosis technique had on the main outcome measures of PGSAS-45 were analyzed. Patients for whom the Kocher maneuver was performed experienced significantly worse meal-related distress and poorer quality of ingestion. Additionally, a less satisfactory physical and mental component summary from the SF-8 was reported. Patients with larger gastric remnants showed significantly better scores on the diarrhea subscale, a slightly better trend for the need for additional meals and dissatisfaction with eating. Regarding the anastomosis technique, there was no difference between the hand-sewn, circular stapler (CS) and linear stapler end-to-end anastomosis, and there was also no difference between the end-to-end and side-to-end anastomosis with the CS. The Kocher maneuver may increase meal-related distress, reduce the quality of ingestion and impart a negative effect on quality of life (QOL). The larger gastric remnants may cause reduction in diarrhea and an improvement in meal-related scores.

P-0054 - The Change of Serum HER2 Extra Cellular Domain Concentration Before and After Resection in Operable Gastric Cancer Patients in Japan; Consider Relations with Pathological HER2 Status by IHC and Fish

Introduction: HER2 extra cellular domain (ECD) can be detected in the serum of healthy person, these concentrations are raised in the patients with cancer; this is dependent on tumor HER2 status and tumor burden. In previous reports, serum HER2-ECD status is useful for judgement of efficacy of anti-HER2 therapy in patients with HER2-positive breast cancer. Although, similarly to breast cancer, approximately 20% gastric cancer show HER2 amplification or overexpression and the efficacy of trastuzumab has been reported, we don't have enough date for serum HER2-ECD of gastric cancer patients.

Strategies for eliminating death from gastric cancer in Japan.

In Japan, efforts have been directed toward improving the detection of early gastric cancer by double contrast radiography and endoscopy, since early cancer has a good prognosis, resulting in Japan having the world’s best diagnostic system for early gastric cancer. The 5-year survival rate of gastric cancer patients in Japan is much higher than in Western countries by the development of endoscopic treatment for early gastric cancer. In February 2013, Japanese national health insurance cover for H. pylori eradication therapy was expanded to patients with H. pylori-associated gastritis, a type of chronic gastritis. H. pylori-associated gastritis causes gastric and duodenal ulcers and gastric polyps, therefore, providing treatment for this gastritis is likely to substantially decrease the prevalence of both gastric and duodenal ulcer and gastric cancer. Patients with gastritis are tested for H. pylori infection and those who are positive receive eradication therapy followed by periodic endoscopic surveillance. If such an approach is pursued further in Japan, gastric cancer deaths will show a dramatic decline after 10–20 years.

Status of tissue expression and serum levels of HER2 in gastric cancer patients in Japan.

The incidence of HER2 expression in gastric cancer varies among previous studies. Furthermore, serum HER2 levels have not been well studied in patients with gastric cancer. Cancerous gastric tissue was analyzed by immunohistochemistry (IHC) to give an IHC score (IHC0, 1+, 2+ or 3) for HER2 expression. Fluorescence in situ hybridization (FISH) was performed to examine HER2 gene expression in IHC2+ cases. Levels of HER2 in serum collected before surgery were determined by chemiluminescent enzyme immunoassay. Subjects were 105 gastric cancer patients who underwent surgical resection. Tissue expression of HER2 was positive (IHC3+, or IHC2+ plus FISH+) in 6.7% of patients (7/105). All HER2-positive tumors were highly differentiated. Mean serum HER2 level was 8.7±2.1 ng/dl in patients with primary gastric cancer. The mean serum HER2 level in the highly differentiated cancer group was 9.2±2.1 ng/dl, which was significantly higher than that (8.1±1.9 ng/dl) in the poorly differentiated group. Tissue expression of HER2 was found in 6.7% of examined Japanese gastric cancer patients, and all HER2-positive tumors were highly differentiated. Serum HER2 levels were significantly higher in patients with highly differentiated cancer, in good agreement with the higher tissue expression of HER2 in highly differentiated cancer.

Current status of treatment strategy for elderly patients with gastric cancer

The World Health Organization (WHO) has defined the chronological age of 65 or older as a definition of ‘‘elderly’’ or older person, and defined the former aged for people from 65 to 74 years, the latter aged for people from 75 to 84 years, and the super aged for people 85 years and more. In industrialized countries, life expectancy has increased consistently over the past decades. Life expectancy (male/ female) in Japan was 18.86/23.89 years for those 65 years old, 11.58/15.38 years for those 75 years old, and 6.18/ 8.30 years for those 85 years old by the complete life table in 2010, respectively. In Japan the population peaked in 2004 and has been decreasing recently. However, the number of people 65 years old and over is increasing continuously, being 23.0 % in 2010; further, 20 % of gastric cancer patients in Japan are more than 80 years old. According to the aging society, the current status of treatment strategy for elderly patients with gastric cancer is discussed. There is controversy regarding strategies for treating elderly patients with gastric cancer. The number of deaths of elderly patients with gastric cancer is increasing, but objective indicators for appropriate criteria of surgery and standard criteria of perioperative complications are not yet established. In the treatment algorithm of the NCCN guideline, there are items of ‘‘medically fit’’ and ‘‘medically unfit,’’ but no definite criteria. There are several prediction scoring systems for postoperative complications such as E-PASS, POSSUM Score, and so on. However, the published research is very limited because of the strict selection and underrepresentation of elderly patients in clinical trials. Elderly patients had significantly more co-morbidities and a poorer nutritional status than younger patients. The presence of co-morbidities was the independent factor affecting morbidity and mortality. In elderly patients, surgical strategies must be modulated on the basis of comorbidities, tumor stage, and future quality of life. It is important to control intraoperative bleeding and to avoid extensive lymph node dissection and combined resection of other organs. Extended lymph node dissection in elderly patients did not influence the 5-year survival rate, and the mortality and morbidity rates in extended lymph node dissection were higher than in limited dissection. Therefore, the surgical intervention had best be minimized. The decision whether to perform surgery for elderly patients should be made according to the individual physical and clinical condition such as favorable respiratory function, cardiac function, performance status, and general condition. Preoperative rehabilitation or training might be somewhat effective. The remote survival rate after curative gastrectomy of the elderly patients was lower than that of the younger patients because there were more non-cancer deaths. However, they also had a good prognosis whether or not other causes of death were considered. Recent improvements in the surgical techniques and perioperative management have made gastrectomy for elderly patients who have no co-morbidities to be safe. Chronological age alone is not sufficient reason to withhold curative or palliative treatment from elderly gastric cancer patients. Patient selection and risk-adapted surgery in elderly patients can obtain an acceptable therapeutic result comparable to that This is an editorial to the article available at doi:10.1007/s10147-012-0482-9.

S-1 combined with cisplatin neoadjuvant chemotherapy in gastric carcinoma

S-1 is a kind of fouth-generation oral fluoropyrimidine,including tegafur(FT),5-chloro-2,4-dihydroxypyridine(CDHP),and potassium oxonate(Oxo).S-1 is now used in 80% advanced gastric cancer patients in Japan,it's reported that CR+RR is over 44.6%.Neoadjuvant chemotherapy can reduce tumor loading,degrade the staging,afford operation possibility.S-1 combined with CDDP as a new neoadjuvant chemotherapy,is the most efficient therapy in advanced gastric cancer at present,it's CR can be over 76%. Key words: Chemotherapy,adjuvant; Stomach neoplasms; Cisplatin; S-1

Safety evaluation of oral fluoropyrimidine S-1 for short- and long-term delivery in advanced gastric cancer: analysis of 3,758 patients

To evaluate the comprehensive safety profile of S-1, a promising novel oral fluoropyrimidine derivative, based on large cohort data. Study subjects were identified from a prospective registry of 3,758 advanced gastric cancer patients in Japan. Each patient was treated with an identical regimen of S-1 monotherapy (40 mg b.i.d. on days 1-28, every 6 weeks) and assessed for all adverse events. The median duration of treatment was 88 days; 1,605 (43%) patients underwent three or more treatment cycles. The relative dose intensity was 0.87 in the first two cycles (short-term treatment period) and 0.89 thereafter (long-term treatment period). Neutropenia was the most common severe (grade 3-4) hematological event (6.3% in the short-term period and 5.3% in the long-term period). Other hematological or key gastrointestinal events (diarrhea, nausea/vomiting, and stomatitis) had a low incidence of severe cases throughout the whole administration period (0.3-3.8%). The time to onset of severe events did not differ between patients with mild renal impairment (creatinine clearance, 50-79 ml/min) and those with normal renal function (>or=80 ml/min) (hazard ratio, 1.04; 95% CI, 0.87-1.23; P = 0.691). S-1 had manageable severe toxicity and allowed good compliance regardless of treatment duration. Prolonged administration of the drug was sustainable.

Predictive value of chemotherapy-induced neutropenia for the efficacy of oral fluoropyrimidine S-1 in advanced gastric carcinoma

Myelosuppression that occurs during chemotherapy has been reported to be a predictor of better survival in patients with breast or lung carcinomas. We evaluated the prognostic implications of chemotherapy-induced neutropenia in advanced gastric carcinoma. Data from a prospective survey of oral fluoropyrimidine S-1 for advanced gastric cancer patients in Japan were reviewed. We identified 1055 untreated patients with adequate baseline bone marrow function. During treatment with S-1, a total of 293 (28%) patients experienced grade 1 or higher neutropenia. The adjusted hazard ratio of death for the presence of neutropenia, as compared with the absence of such toxicity, from a multivariate Cox model was 0.72 (95% confidence interval, 0.54–0.95; P=0.0189) for grade 1 neutropenia, 0.63 (0.50–0.78; P<0.0001) for grade 2 neutropenia and 0.71 (0.51–0.98; P=0.0388) for grade 3–4 neutropenia. These findings suggest that the occurrence of neutropenia during chemotherapy is an independent predictor of increased survival in patients with advanced gastric cancer, whereas the absence of such toxicity indicates that the dosages of drugs are not pharmacologically adequate. Monitoring of neutropenia in patients who receive chemotherapy may contribute to improved drug efficacy and favourable survival.

A single nucleotide polymorphism in the extracellular domain of TRAIL receptor DR4 at nucleotide 626 in gastric cancer patients in Japan

Death receptor 4 (DR4) is a member of the tumor necrosis factor-related apoptosis-inducing ligand receptor genes. A single nucleotide polymorphism (Thr or Arg, C or G) in the extracellular domain was reported to be associated with a risk of lung cancer, head and neck cancer, and bladder cancer. In this study, we examined the association between the DR4 polymorphism and gastric cancer. The Thr/Thr, Thr/Arg and Arg/Arg genotypes were found in 250 (91.2%), 23 (8.4%) and 1 (0.4%) of 274 gastric cancer patients and in 317 (92.2%), 21 (6.1%) and 6 (1.7%) of 344 control subjects, respectively. The OR of Thr/Arg or Arg/Arg genotype did not reveal a significantly enhanced risk of 1.13 (95% CI, 0.63-2.00) compared to Thr/Thr genotype, suggesting that the DR4 polymorphism did not modify the risk of gastric cancer. In patients, no association between the genotype and clinicopathological characteristics (depth of invasion, lymph node metastasis, distant metastasis, stage and grade of differentiation) of gastric carcinoma was found. DR4 was constantly expressed in gastric carcinoma, but not in non-neoplastic gastric epithelium in immunohistochemistry. In conclusion, a Thr to Arg single nucleotide polymorphism in the extracellular domain of DR4 could not be associated with the development and progression of gastric cancer.

Gastric cancer surgery in the elderly.

Although there is a decreasing number of gastric cancer patients in Japan, the number of patients over 80 years of age is increasing. Forty patients over 80 years of age (from 80 to 88 years) with gastric cancer (Group 1) during the 10 years from 1980 to 1989 were retrospectively investigated and compared with those 70-79 years of age (Group 2). The resectability rate was 80% in Group 1 and 89% in Group 2. Early gastric cancer was observed at a rate of only 25% in Group 1 and 39% in Group 2. Pathologically, the differentiated type occurred in 78% of those in Group 1 and 68% of Group 2. Total gastrectomy was performed in only 6% of the resected cases in Group 1 and in 25% of Group 2. A combined resection including such operations as pancreatico-splenectomy or splenectomy (PS) was employed in none of the total gastrectomy cases in Group 1 and in 30% of Group 2. R3 gastrectomy was performed in none of the patients in Group 1 and in 21% of those in Group 2. Postoperative complications occurred in 25% of Group 1 patients and in 12% of Group 2 patients. Anastomotic leakage occurred in 3% of those in Group 1 and in 4% of those in Group 2. The 5-year survival rate was 47% for all the resected cases in Group 1 and 68% for Group 2. The 5-year survival rate was 61% for those who underwent a curative (radical) gastrectomy in Group 1, and 84% for those in Group 2.