Mission of the National Cancer Center Hospital in Japan to promote clinical trials for precision medicine

Precision medicine is a growing field worldwide.Despite its potential benefit to many patients,several major obstacles must be overcome before precision medicine can be more widely used in clinical practice.The main obstacles are associated with the quality of samples used for genomic analysis。

Non-robotic minimally invasive gastrectomy as an independent risk factor for postoperative intra-abdominal infectious complications: A single-center, retrospective and propensity score-matched analysis

BACKGROUND Minimally invasive surgery for gastric cancer(GC) has gained widespread use as a safe curative procedure especially for early GC.AIM To determine risk factors for postoperative complications after minimally invasive gastrectomy for GC.METHODS Between January 2009 and June 2019, 1716 consecutive patients were referred to our division for primary GC. Among them, 1401 patients who were diagnosed with both clinical and pathological Stage Ⅲ or lower GC and underwent robotic gastrectomy(RG) or laparoscopic gastrectomy(LG) were enrolled. Retrospective chart review and multivariate analysis were performed for identifying risk factors for postoperative morbidity.RESULTS Morbidity following minimally invasive gastrectomy was observed in 7.5% of the patients. Multivariate analyses demonstrated that non-robotic minimally invasive surgery, male gender, and an operative time of ≥ 360 min were significant independent risk factors for morbidity. Therefore, morbidity was compared between RG and LG. Accordingly, propensity-matched cohort analysis revealed that the RG group had significantly fewer intra-abdominal infectious complications than the LG group(2.5% vs 5.9%, respectively;P = 0.038), while no significant differences were noted for other local or systemic complications.Multivariate analyses of the propensity-matched cohort revealed that non-robotic minimally invasive surgery [odds ratio = 2.463(1.070–5.682);P = 0.034] was a significant independent risk factor for intra-abdominal infectious complications.CONCLUSION The findings showed that robotic surgery might improve short-term outcomes following minimally invasive radical gastrectomy by reducing intra-abdominal infectious complications.

Prognostic factors of minimally invasive surgery for gastric cancer: Does robotic gastrectomy bring oncological benefit?

BACKGROUND Gastric cancer is the third leading cause of cancer-related death worldwide and surgical resection remains the sole curative treatment for gastric cancer.Minimally invasive gastrectomy including laparoscopic and robotic approaches has been increasingly used in a few decades.Thus far,only a few reports have investigated the oncological outcomes following minimally invasive gastrectomy.AIM To determine the 5-year survival following minimally invasive gastrectomy for gastric cancer and identify prognostic predictors.METHODS This retrospective cohort study identified 939 patients who underwent gastrectomy for gastric cancer during the study period.After excluding 125 patients with non-curative surgery(n=77),other synchronous cancer(n=2),remnant gastric cancer(n=25),insufficient physical function(n=13),and open gastrectomy(n=8),a total of 814 consecutive patients with primary gastric cancer who underwent minimally invasive R0 gastrectomy at our institution between 2009 and 2014 were retrospectively examined.Accordingly,5-year overall and recurrence-free survival were analyzed using the Kaplan–Meier method with the log-rank test and Cox regression analyses,while factors associated with survival were determined using multivariate analysis.RESULTS Our analysis showed that age>65 years,American Society of Anesthesiologists(ASA)physical status 3,total or proximal gastrectomy,and pathological T4 and N positive status were independent predictors of both 5-year overall and recurrencefree survival.Accordingly,the included patients had a 5-year overall and recurrence-free survival of 80.3%and 78.2%,respectively.Among the 814 patients,157(19.3%)underwent robotic gastrectomy,while 308(37.2%)were diagnosed with pathological stage II or III disease.Notably,our findings showed that robotic gastrectomy was an independent positive predictor for recurrence-free survival in patients with pathological stage II/III[hazard ratio:0.56(0.33-0.96),P=0.035].Comparison of recurrence-free survival between the robotic and laparoscopic approach using propensity score matching analysis verified that the robotic group had less morbidity(P=0.005).CONCLUSION Age,ASA status,gastrectomy type,and pathological T and N status were prognostic factors of minimally invasive gastrectomy,with the robot approach possibly improving long-term outcomes of advanced gastric cancer.

Monocyte-derived fibrocytes elimination had little contribution on liver fibrosis

Background:Monocyte-derived fibrocytes play an important role in the progression of fibrosis in the skin,lungs,heart and kidney.However,the contribution of fibrocytes to liver fibrosis is unclear.The aim of this study was to investigate whether fibrocytes contributed to fibrosis progression in the livers of carbon tetrachloride(CCl 4)-treated mice.Methods:C57BL/6J mice were divided into 4 groups:normal control group,CCl 4-treated group,CCl 4+control liposome-treated group,and CCl 4+clodronate liposome-treated group.For the elimination of systemic monocyte and monocyte-derived fibrocyte,one group was treated with clodronate liposome,and another group with control liposome as a control.After 4 weeks of treatment,hepatic mononuclear cells were subjected to immunofluorescent(IF)staining and fluorescence-activated cell sorter(FACS)analysis to detect fibrocytes.Measurement of collagen-positive Sirius red stained area and collagen-I mRNA expression in the liver were performed to evaluate the degree of liver fibrosis quantitatively.Results:In the liver of the CCl 4-treated and CCl 4+control liposome-treated groups,the number of fibrocytes,the area positive for Sirius red staining and collagen-I mRNA expression significantly increased compared with those in the normal control group.In the liver of the CCl 4+clodronate liposome-treated group,few fibrocytes was observed as in the normal control group,but Sirius red staining positive area and collagen-I mRNA expression were increased and equivalent to the CCl 4-treated and CCl 4+control liposome-treated groups.Conclusion:Monocyte-derived fibrocytes play a minimal role in CCl 4-induced liver fibrosis.Cells other than fibrocytes such as hepatic stellate cells play a central role in liver fibrosis.

Efficacy and safety of sofosbuvir and ledipasvir in Japanese patients aged 75 years or over with hepatitis C genotype 1

AIM To evaluate the efficacy and safety of a regimen containing sofosbuvir(SOF) and ledipasvir(LDV) in Japanese patients aged ≥ 75 years with hepatitis C genotype 1.METHODS This multicenter, retrospective study consisted of 246 Japanese patients with HCV genotype 1 at nine centers in Miyazaki prefecture in Japan. Demographic, clinical, virological, and adverse effects(AE)-related data obtained during and after SOF/LDV therapy were collected from medical records. These patients were divided into two groups, younger(aged < 75 years) and elderly(aged ≥ 75 years). Virological data and AEs were analyzed by age group.RESULTS The sustained virological response(SVR) rates at 12 wk after treatment were 99.2%, 99.4%, and 98.7% in the overall population and in patients aged < 75 and ≥ 75 years, respectively. Common AEs during therapy were headache, pruritus, constipation, and insomnia. These occurred in fewer than 10% of patients, and their incidence was not significantly different between the younger and elderly groups. Two patients discontinued treatment, one due to a skin eruption and the other due to cerebral bleeding. CONCLUSION Compared with younger patients, elderly patients had a similar virological response and tolerance to SOF/LDV therapy.

Circulating tumor cells in gastric cancer

Circulating tumor cells(CTCs)have received a lot of attention as a novel biomarker for cancer research in past decades.CTCs infiltrate the bloodstream derived from the primary tumor,and are significantly involved in cancer metastasis and recurrence.Although clinical applications have been challenging owing to the difficulties of CTC identification,recent development of technology for specific enrichment and detection of CTCs contributes to diagnosis and treatment.Furthermore,CTC analyses will shed new light on the biological mechanisms of cancer progression and metastasis.A number of clinical studies have already been carried out on the basis of CTC technology.Nevertheless,the clinical utility of CTCs is still unknown in gastric cancer.In this review,we elaborate on the latest advances of CTC research in gastric cancer.

Overview of genetic and epigenetic alterations in the pathogenesis of esophagogastric junctional adenocarcinoma and esophageal adenocarcinoma: recent fi ndings by next generation sequencing

Esophagogastric junctional adenocarcinoma is commonly treated as esophageal adenocarcinoma(EAC)and has dramatically increased in Western countries for several decades.The similar trend has been observed in Asian countries(not in China).Barrett’s esophagus(BE)is a widely accepted precursor of EAC.Recent advances of next-generation sequencing could provide researchers with a better understanding of genetic and epigenetic alterations in the carcinogenesis of EAC.In this review,we have summarized the recently reported major genetic and epigenetic alterations in both BE and EAC.Sonic hedgehog/bone morphogenetic protein axis,which is a key signaling for esophageal development,plays an important role in BE intestinal metaplasia.Single nucleotide polymorphisms related to esophageal organogenesis,such as FOXF1 and FOXP3,are frequently detected in BE patients.During the progression of BE to adenocarcinoma,lacking of normal function of TP53 and CDKN2A by loss of heterozygosity(LOH),mutation,or promoter methylation has been frequently observed.LOH at 9p(coding CDKN2A)is an earlier event to EAC carcinogenesis compared to that at 17q(coding TP53)LOH.In order to further elucidate the pathogenesis of BE and EAC,it will be necessary to analyze these genetic/epigenetic alterations in combination with clinical data in a large-scale cohort.