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1.
World J Surg ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31953612

RESUMO

BACKGROUND: Surgery for gastric cancer should be performed as soon as possible after diagnosis. However, sometimes the waiting time for surgery tends to be longer. The relation between the waiting time for surgery and survival in patients with gastric cancer remains to be fully investigated. METHODS: This retrospective, single-center cohort study evaluated patients with gastric cancer who underwent curative surgery from 2006 through 2012 at Kanagawa Cancer Center in Japan. Patients who received neoadjuvant chemotherapy were excluded. The waiting time for surgery was defined as the time between the first visit and surgery. We investigated whether the waiting time for surgery has a linear negative impact on outcomes by using a Cox regression model with clinical prognostic factors. RESULTS: In total, 801 patients were eligible. The median waiting time was 45 days (range 10-269 days). The restricted cubic spline regression curve showed that the adjusted time-specific hazard ratios of waiting times did not indicate a linear negative trend on survival between 20 and 100 days (p = 0.759). In the Cox model with a quartile of waiting times, waiting times in the 32-44-day group, 43-62-day group, and ≥63 day groups were not associated with poorer overall survival as compared with the ≤31 day group (HR: 1.01, 95% CI 0.63-1.60, p = 0.984, HR: 1.17, 95% CI 0.70-1.94, p = 0.550, HR: 1.06, 95% CI 0.60-1.88, p = 0.831, respectively). CONCLUSIONS: There was no negative relation between the waiting time for surgery (within 100 days) and survival in patients with gastric cancer.

2.
Future Oncol ; 16(4): 31-38, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31920105

RESUMO

Background: Although surgical resection is necessary to cure the locally advanced gastric cancer, it is sometimes difficult for extensive nodal metastasis such as para-aortic nodal disease or bulky nodal metastasis around the major gastric branched arteries. We had conducted several Phase II studies and clarified preoperative chemotherapy with doublet regimen followed by surgery markedly improved the survival for this disease. Recently, preoperative chemotherapy with docetaxel, oxaliplatin and S-1 (DOS) showed promising efficacy and acceptable feasibility for resectable advanced gastric cancer. Aim: To describe the design and rationale for the multi-institutional, single-arm, Phase II trial of systemic chemotherapy with DOS followed by surgery in advanced gastric cancer with extensive lymph node metastasis (JCOG1704). If efficacy and safety of DOS can be shown, we will conduct a Phase III trial comparing preoperative DOS and current standard cisplatin and S-1. Trial registration: jRCTs031180028.

3.
Anticancer Res ; 40(1): 405-412, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892594

RESUMO

BACKGROUND/AIM: To evaluate the outcomes of curative resection for Borrmann type IV gastric cancer through an analysis of the clinical, surgical and pathological data and through identifying which of these prognostic factors are associated with survival. PATIENTS AND METHODS: We retrospectively analyzed 2798 patients who had undergone excision of the primary lesion and 122 patients with type IV gastric cancer undergoing curative resection (R0 or 1) at Yokohama City University Hospital and Kanagawa Cancer Center between November 1995 and May 2016. RESULTS: Borrmann type IV gastric cancer had more advanced and unfavorable clinicopathological factors compared to other types. The 5-year overall survival rate was 28%, and the median survival was 21.8 months. The overall survival rate was influenced by the depth of invasion, lymph node metastasis, peritoneal lavage cytology (CY), stage and intraoperative blood loss. Of these, independent prognostic factors were intraoperative blood loss (<400 vs. ≥400 ml, risk ratio 1.64; p=0.045) and CY (0 vs. 1, risk ratio 2.25; p=0.004). CONCLUSION: The control of intraoperative bleeding had a positive impact on the survival of patients receiving curative resection for Borrmann type IV gastric cancer.


Assuntos
Perda Sanguínea Cirúrgica , Cuidados Intraoperatórios , Neoplasias Gástricas/cirurgia , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/patologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
4.
Lancet Gastroenterol Hepatol ; 5(2): 142-151, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31757656

RESUMO

BACKGROUND: Laparoscopy-assisted distal gastrectomy (LADG) is increasingly being used as an alternative to open distal gastrectomy (ODG) for gastric cancer treatment. Retrospective studies have shown equivalent survival with the two procedures, but these studies are limited by selection bias because LADG is more technically difficult than ODG. We aimed to evaluate whether LADG was non-inferior to ODG in terms of long-term survival outcomes. METHODS: We did an open-label, multicentre, non-inferiority, phase 3 randomised controlled trial at 33 institutions in Japan. Patients aged 20-80 years with histologically confirmed gastric adenocarcinoma (T1N0, T1N1, or T2[MP]N0), clinical stage I, in the middle or lower third of the stomach, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, with a body-mass index of less than 30 kg/m2, were randomly assigned (1:1) to receive ODG or LADG. Randomisation was done by telephone, fax, or with a web-based system in the Japan Clinical Oncology Group Data Center; a minimisation method with a random component was used to adjust for institution and clinical stage (IA or IB). Only study-accredited surgeons performed ODG and LADG. The primary endpoint was relapse-free survival and was analysed according to the intention-to-treat principle. The non-inferiority margin (LADG vs ODG) was set at a hazard ratio (HR) of 1·54. The trial was registered with the UMIN Clinical Trials Registry, UMIN000003319. FINDINGS: Between March 15, 2010, and Nov 29, 2013, 921 patients were enrolled and randomly assigned to receive ODG (n=459) or LADG (n=462). 912 (99%) participants had the assigned surgery. 5-year relapse-free survival was 94·0% (95% CI 91·4-95·9) in the ODG group and 95·1% (92·7-96·8) in the LADG group. LADG was non-inferior to ODG for relapse-free survival (HR 0·84 [90% CI 0·56-1·27]), p=0·0075). The most common grade 3 or 4 adverse event was bowel obstruction, occurring in 11 (2%) of 455 patients in the ODG group and five (1%) of 457 patients in the LADG group. There were no treatment-related deaths. INTERPRETATION: This trial supports the non-inferiority of LADG compared with ODG for clinical stage I gastric cancer relapse-free survival, suggesting that LADG should be considered a standard treatment option when performed by experienced surgeons. FUNDING: Japan National Cancer Center, Ministry of Health, Labour and Welfare of Japan, Japan Agency for Medical Research and Development.

5.
Eur J Cancer ; 124: 67-76, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31759294

RESUMO

The aim of this manuscript is to discuss the viewpoint of the European Organisation for Research and Treatment of Cancer (EORTC) Gastric Cancer Taskforce and Japan Clinical Oncology Group (JCOG) Gastric Cancer Study Group on the current challenges in the multidisciplinary management of stage II-III gastric and gastro-oesophageal junction (GEJ) cancer. We seek to outline how these challenges are addressed in current trials of both groups. Key elements of future trials of EORTC and JCOG in this indication are described, and a joint vision on how multidisciplinary research of gastric and GEJ cancer patients should be organised is outlined.

6.
Int J Clin Oncol ; 25(2): 301-311, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31620931

RESUMO

BACKGROUND: The phase III JACOB trial (NCT01774786) compared the efficacy and safety of pertuzumab and trastuzumab plus chemotherapy with placebo and trastuzumab plus chemotherapy in patients with previously untreated human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric or gastroesophageal junction cancer. We conducted a subgroup analysis in Japanese patients. METHODS: Patients were randomized 1:1 to pertuzumab 840 mg or placebo, plus trastuzumab (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) and chemotherapy (cisplatin 80 mg/m2, and capecitabine 1000 mg/m2 twice daily for 28 doses or 5-fluorouracil 800 mg/m2 every 24 h for 120 h), every 3 weeks. Continuation of chemotherapy after 6 cycles was at the discretion of the patient and the treating physician. RESULTS: A total of 40 Japanese patients were included in each arm. Median overall survival was 22.0 months (95% confidence interval [CI] 13.8-not evaluable) and 15.6 months (95% CI 9.7-19.2) in the pertuzumab and placebo arms, respectively (hazard ratio [HR] 0.64 [95% CI 0.37-1.10]). Median progression-free survival was 12.4 months (95% CI 6.1-14.1) in the pertuzumab arm and 6.3 months (95% CI 4.3-8.1) in the placebo arm (HR 0.50 [95% CI 0.30-0.82]). Grade ≥ 3 adverse events and serious adverse events were more frequent in the pertuzumab arm than the placebo arm. CONCLUSIONS: Results from this subgroup analysis of the JACOB trial suggest similar efficacy of pertuzumab in Japanese patients and patients in the overall population, encouraging continued investigation of new agents for gastric cancer in Japanese patients.

7.
J Cancer Res Clin Oncol ; 146(1): 75-86, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31754833

RESUMO

PURPOSE: The enzymes gamma-glutamyl hydrolase (GGH) and folylpolyglutamate synthetase (FPGS) regulate intracellular folate concentrations needed for cell proliferation, DNA synthesis, and repair. High GGH expression affects 5-FU thymidylate synthase (TS) inhibition and is a risk factor for various malignancies. Here, the clinical significance of GGH and FPGS expression was investigated in Stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1. METHODS: Surgical specimens of cancer tissue and adjacent normal mucosa, obtained from 253 patients with previously untreated gastric cancer, were examined. GGH and FPGS mRNA expression was measured by qPCR to evaluate their clinicopathological significance in gastric cancer patients after curative resection. RESULTS: While FPGS expression showed no significant differences between the cancerous and normal samples, GGH expression was higher in cancer tissue than in adjacent normal mucosa. High GGH expression was correlated with age, histological type, and vascular invasion. Overall survival (OS) of patients with high GGH mRNA expression was significantly poorer than of patients with low GGH expression. Multivariate analysis showed that high GGH expression was an independent prognostic factor of OS (HR: 2.58, 95% CI 1.29-5.16). Patients who received S-1 adjuvant treatment showed a significantly poor OS between high GGH/low FPGS and low GGH/high FPGS. Patients without adjuvant treatment showed no significant difference. CONCLUSION: GGH expression was significantly higher in gastric cancer tissue than in adjacent normal mucosa. High GGH and low FPGS expression is a useful independent predictor of poor outcomes in stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/biossíntese , Peptídeo Sintases/biossíntese , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/enzimologia , gama-Glutamil Hidrolase/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Quimioterapia Adjuvante , Combinação de Medicamentos , Feminino , Mucosa Gástrica/enzimologia , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ácido Oxônico/administração & dosagem , Peptídeo Sintases/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Tegafur/administração & dosagem , gama-Glutamil Hidrolase/genética
8.
Gastric Cancer ; 23(1): 143-153, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31087200

RESUMO

BACKGROUND: Data on immune checkpoint inhibitor efficacy in patients with human epidermal growth factor receptor 2-positive (HER2+) advanced gastric/gastroesophageal junction (G/GEJ) cancer are lacking. Because HER2 status was not captured in the ATTRACTION-2 trial, we used patients with prior trastuzumab use (Tmab+) as surrogate for HER2 expression status to evaluate the efficacy and safety of nivolumab as third- or later-line therapy in these patients. METHODS: In ATTRACTION-2, a randomized, double-blind, placebo-controlled, phase 3 multicenter trial, patients were randomized (2:1) to receive nivolumab (3 mg/kg) or placebo every 2 weeks until disease progression or toxicity requiring study discontinuation. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety were assessed. RESULTS: Of 493 enrolled patients, 81 (nivolumab, n = 59; placebo, n = 22) were Tmab+ and 412 (nivolumab, n = 271; placebo, n = 141) were Tmab-. In both groups, patients receiving nivolumab showed a longer median OS vs placebo (Tmab+, 8.3 [95% confidence interval, 5.3-12.9] vs 3.1 [1.9-5.3] months, hazard ratio, 0.38 [0.22-0.66]; P = 0.0006; Tmab-, 4.8 [4.1-6.0] vs 4.2 [3.6-4.9] months, 0.71 [0.57-0.88]; P = 0.0022). PFS was longer in both groups receiving nivolumab vs placebo (Tmab+, 1.6 [1.5-4.0] vs 1.5 [1.3-2.9] months, 0.49 [0.29-0.85]; P = 0.0111; Tmab-, 1.6 [1.5-2.4] vs 1.5 [1.5-1.5] months, 0.64 [0.51-0.80]; P = 0.0001). CONCLUSIONS: Nivolumab was efficacious and safe as third- or later-line therapy regardless of prior trastuzumab use in patients with advanced G/GEJ cancer.

9.
Gastric Cancer ; 23(1): 195-201, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31302790

RESUMO

BACKGROUND: Curative surgery for remnant gastric cancer (RGC) after gastrectomy for gastric cancer (GC) can be challenging. We examined the risk factors for lymph node metastasis in RGC, especially for tumors located at the greater curvature (G) or non-greater curvature (NG), to determine the appropriate indications of curative surgery. METHODS: Data from the two high-volume centers of Japan between 1998 and 2018 were retrospectively reviewed. Among the 137 patients enrolled in this study, 34 were classified as the G group and 103 as the NG group. The incidence of lymph node metastasis and its risk factors was evaluated. RESULTS: Lymph node metastasis was observed in 21.2% (29/137), including 38.2% (13/34) in the G group and 15.5% (16/103) in the NG group (p = 0.008). A logistic regression analysis showed that tumor location of G or NG (p = 0.042), tumor size (p = 0.002) and depth of invasion (p = 0.009) were significant independent risk factors for nodal metastasis. Risk classification using these factors showed that clinical T1-T2 with a maximum size < 35 mm located at the non-greater curvature had the lowest nodal metastatic risk (4.3%). CONCLUSIONS: Tumor location at the G or NG was a significant risk factor for nodal metastasis in RGC. When selecting curative surgery for RGC, physicians should consider the nodal metastatic risk calculated by the tumor location, size and depth of invasion.

10.
In Vivo ; 34(1): 461-467, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31882514

RESUMO

BACKGROUND/AIM: Endothelial cell-specific molecule-1 (ESM-1) is a soluble proteoglycan which has important role in various biological events. We investigated the impact of the ESM-1 expression in cancer tissues on outcomes in stage II/III gastric cancer patients who received adjuvant S-1 chemotherapy. PATIENTS AND METHODS: The ESM-1 mRNA expression in cancerous tissues and adjacent normal mucosa from 253 patients was measured. The associations between the ESM-1 gene expression and the survival and clinicopathological features were investigated. RESULTS: A significant association was observed between high ESM-1 expression and undifferentiated adenocarcinoma. The overall survival curve was significantly lower in patients with high ESM-1 expression than in those with low expression (p=0.005). High ESM-1 expression was a significant independent prognosticator (HR=2.291, p=0.007). CONCLUSION: ESM-1 gene expression in cancerous tissues is an important prognosticator in stage II/III gastric cancer patients who received adjuvant S-1 chemotherapy.

11.
Anticancer Res ; 39(12): 6567-6573, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810922

RESUMO

BACKGROUND/AIM: The KIAA1199 gene has been associated with cancer-cell proliferation, but its functions remain poorly studied. Here, we examined the clinical significance of the KIAA1199 mRNA levels in locally advanced gastric cancer (GC). Materials and Methods/Results: Using samples from 254 patients with stage II/III GC, we found significantly higher KIAA1199 levels in cancerous tissues compared to adjacent normal mucosa (ANM). There was no significant relationship between KIAA1199 expression and clinical features. Although overall survival rates (OSR) of patients, who underwent surgery did not correlate with KIAA1199 expression, patients who underwent adjuvant chemotherapy with S-1 and had high KIAA1199 levels displayed significantly lower OSR. KIAA1199 knock down (KIAA1199-KD) suppressed proliferation, invasiveness, and sensitivity of GC cells to 5-fluorouracil (5-FU). CONCLUSION: KIAA1199 expression appears to be a promising prognostic marker in patients with locally advanced GC, who underwent postoperative adjuvant chemotherapy with S-1. KIAA1199 may represent a novel target for GC pharmacotherapy.


Assuntos
Hialuronoglucosaminidase/genética , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/terapia , Tegafur/uso terapêutico , Regulação para Cima , Idoso , Linhagem Celular Tumoral , Proliferação de Células , Quimioterapia Adjuvante , Procedimentos Cirúrgicos do Sistema Digestório , Combinação de Medicamentos , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Análise de Sobrevida
12.
Gastric Cancer ; 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31863227

RESUMO

BACKGROUND: Nivolumab showed improvement in overall survival (OS) in ATTRACTION-2, the first phase 3 study in patients with gastric/gastroesophageal junction (G/GEJ) cancer treated with ≥ 2 chemotherapy regimens. The 2-year follow-up results of ATTRACTION-2 are presented herein. METHODS: ATTRACTION-2 was a randomized, double-blind, placebo-controlled, phase 3 trial (49 sites; Japan, South Korea, and Taiwan). The median (min-max) follow-up period was 27.3 (24.1-36.3) months. The primary endpoint was OS. A subanalysis of OS was performed based on best overall response and tumor-programmed death ligand-1 (PD-L1) expression status. RESULTS: Overall, 493 of 601 screened patients were randomized (2:1) to receive nivolumab (330) or placebo (163). OS (median [95% confidence interval; CI]) was significantly longer in the nivolumab group (5.26 [4.60-6.37] vs 4.14 [3.42-4.86] months in placebo group) at the 2-year follow-up (hazard ratio [95% CI], 0.62 [0.51-0.76]; P < 0.0001). A higher OS rate was observed in the nivolumab vs placebo group at 1 (27.3% vs 11.6%) and 2 years (10.6% vs 3.2%). The OS benefit was observed regardless of tumor PD-L1 expression. Among patients with a complete or partial response (CR or PR) in the nivolumab group, the median OS (95% CI) was 26.6 (21.65-not applicable) months; the OS rates at 1 and 2 years were 87.1% and 61.3%, respectively. No new safety signals were identified. CONCLUSIONS: Nivolumab treatment resulted in clinically meaningful long-term improvements in OS in patients with previously treated G/GEJ cancer. The long-term survival benefit of nivolumab was most evident in patients with a CR or PR.

13.
J Cancer ; 10(22): 5527-5535, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632496

RESUMO

Background: The aim of this study was to determine whether or not the short- and long-term outcomes were affected by the age-adjusted Charlson comorbidity index (ACCI) in patients who underwent curative resection for gastric cancer. Methods: The patients were retrospectively selected from among the medical records of consecutive patients who underwent curative gastrectomy with nodal dissection for gastric cancer at Yokohama City University and Kanagawa Cancer Center from January 2000 to August 2015. Results: A total of 2254 patients were eligible for inclusion in the present study. One thousand six hundred fifty-six patients had an ACCI of <6 points (ACCI low group), while 598 had a score of ≥6 points (ACCI high group). The median age (p<0.001) and American Society of Anesthesiologists physical status (ASA-PS) score (p<0.001) of the ACCI high group were higher in comparison to the ACCI low group. The incidence of surgical complications in the ACCI high group was significantly higher than that in the ACCI low group (12.0% vs. 7.2%, p<0.001). Univariate and multivariate analyses demonstrated that an ACCI high classification was a significant risk factor for postoperative complications. In addition, the 5-year OS rates of the ACCI low and ACCI high groups were 85.4% and 74.1%, respectively. The difference was statistically significant (p<0.001). The univariate and multivariate analyses demonstrated that an ACCI high classification was a significant prognostic factor for OS. Conclusions: Our results support that a high ACCI value is an independent risk factor for the short- and long-term outcomes of patients with gastric cancer. To improve the survival of patients with gastric cancer, it is necessary to carefully plan the perioperative care and the surgical strategy according to the ACCI.

14.
J Cancer ; 10(21): 5130-5138, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31602266

RESUMO

Purpose: A comprehensive molecular analysis was conducted to identify prognostic and predictive markers for adjuvant S-1 chemotherapy in stage II/III Japanese gastric cancer (GC) patients and to evaluate their potential suitability for alternative cytotoxic or targeted drugs. Experimental Design: We investigated genetic polymorphisms of enzymes potentially involved in 5-fluoruracil (5-FU) metabolism as well as platinum resistance, previously identified genomic subtypes potentially predicting 5-FU benefit, and mRNA expression levels of receptor tyrosine kinases and KRAS as potential treatment targets in a single institution cohort of 252 stage II/III GC patients treated with or without S-1 after D2 gastrectomy. Results: 88% and 62% GC had a potentially 5-FU sensitive phenotype by SNP analyses of TS 3'UTR, and TS 5'UTR, respectively. 24%, 46%, 40%, 5%, and 44% GC had a potentially platinum sensitive phenotype by SNP analyses of GSTP1, ERCC1 rs11615, ERCC1 rs3212986, ERCC2, and XRCC1, respectively. High HER2, EGFR, FGFR2, or MET mRNA expression was observed in 49%, 66%, 72%, and 54% GC, respectively. High HER2 expression was the only significant prognosticator (HR=3.912, 95%CI: 1.706-8.973, p=0.0005). High HER2 (p=0.031), low EGFR (p=0.124), high MET (p=0.165) RNA expression, and TS 5'UTR subtype 2R/2R, 2R/3C, or 3C (p=0.058) were significant independent predictors for S-1 resistance. Conclusions: The present study suggests that platinum-based or RTK targeted agents could be alternative treatment options for a substantial subgroup of Japanese GC patients currently treated with S-1. HER2, EGFR, MET, and TS 5'UTR SNP appear to be promising predictive markers for S-1 resistance warranting validation in an independent GC series.

15.
BMJ Open ; 9(9): e026002, 2019 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-31542733

RESUMO

OBJECTIVES: Recent meta-analyses of eradication therapy in Helicobacter pylori-infected adults reported significant reductions in gastric carcinoma risk. However, concerns about supporting unfocused screening and eradication programme in healthy, asymptomatic populations have arisen. We performed a systematic review and Bayesian meta-analysis to provide an accurate interpretation of randomised evidence on the preventive effectiveness of eradication therapy on gastric carcinoma risk. METHODS: We searched databases including PubMed, Cochrane Central and Embase for reference and citation tracking without language restrictions, from inception through 31 July 2018. Paired investigators independently selected randomised controlled trials (RCTs) comparing eradication therapy with placebo or no treatment for asymptomatic or dyspeptic H. pylori-infected adults with no previous gastric carcinoma. The main outcome was gastric carcinoma incidence; secondary outcomes included gastric carcinoma-specific, non-gastric carcinoma and all-cause mortality. RESULTS: A total of 5 population-based and 2 outpatient care-based RCTs involving 7303 adults were eligible. Eradication algorithms were heterogeneous, and unsuccessful eradication and reinfection were frequently observed. A Bayesian meta-analysis with competing risk outcomes found low-certainty evidence that eradication therapy might be more likely than control to reduce gastric carcinoma risk (HR=0.65; 95% credible interval (CrI) 0.41 to 1.0; I2 =11%). The CrIs included the null effects across the subgroup and sensitivity analyses, apart from those based on particular models that excluded two RCTs that enrolled subjects with specific histological findings only (HR=0.55; CrI 0.30 to 0.89; I2 =14%). The uncertainty of the average 41% risk reduction in gastric carcinoma-specific mortality included a clinically important mortality risk increase (HR=0.59 favouring eradication therapy; CrI 0.25 to 1.20; I2 =13%; low certainty). CONCLUSIONS: There is insufficient evidence to support or refute the effectiveness of eradication therapy in preventing gastric carcinoma in H. pylori-infected, high-risk populations. Rigorously conducted large RCTs of healthy infected adults only would provide evidence of the true efficacy of successful eradication. PROSPERO registration number: CRD42014009245.

16.
Gastric Cancer ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31512081

RESUMO

BACKGROUND: Whether or not surgery alone is sufficient for treating patients with pathological stage T1N2M0 (Stage IIA), T1N3a/bM0 (Stage IIB/IIIB), and T3N0M0 (Stage IIA) gastric cancer who were not indicated for adjuvant treatment according to the Japanese gastric cancer treatment guideline remains unclear. METHODS: We retrospectively reviewed the clinical records of 236 patients who had been diagnosed with pT1N2-3b/pT3N0 gastric cancer and undergone R0 gastrectomy with lymph node dissection between January 2000 and December 2012 at the National Cancer Center Hospital, Japan. RESULTS: The 5-year recurrence-free survival (RFS) rates (95% confidence interval [CI]) of the patients with pathological (p) T1N2-3b and T3N0 cancer were 73.9% (63.1-84.7) and 89.5% (84.0-95.0), respectively. The only significant prognostic factors for the survival identified by a multivariate Cox regression analysis in patients with pT1N2-3 cancer were the pN stage (N3a/N2: hazard ratio [HR] 2.940, 95% CI 1.314-5.577; N3b/N2: HR 8.688, 95% CI 3.096-24.382) and tumor diameter (<30/ ≥ 30 mm) (HR 2.919; 95% CI 1.351-6.304). We divided the patients with pT1N2-3 gastric cancer into 3 risk categories (high, moderate, low) using these 2 significant prognostic factors and found that the 5-year RFS rates were significantly different among the 3 risk groups (low risk, 93.0%; moderate risk, 66.7%; high risk, 25.0%; P < 0.001). CONCLUSIONS: pT3N0 and large pT1N2 with a diameter ≥ 30 mm had an excellent prognosis, while pT1N2-3 with at least N3a/b or a tumor diameter < 30 mm showed a relatively poor prognosis. These patients may be candidates for adjuvant chemotherapy.

17.
Ann Surg ; 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31404008

RESUMO

MINI: A prospective nationwide multicenter study revealed that total gastrectomy and para-aortic nodal dissection were not needed for esophagogastric junction tumors. Subtotal esophagectomy with dissection of upper mediastinal station 106recR should be selected if esophageal involvement exceeds 4.0 cm. Lower mediastinal station 110 should be dissected if esophageal involvement exceeds 2.0 cm. OBJECTIVE: The aim of the study was to determine the optimal extent of lymph node dissection for the 2 histological types of esophagogastric junction (EGJ) tumors based on the incidence of metastasis in a prospective nationwide multicenter study. BACKGROUND: Because most previous studies were retrospective, the optimal surgical procedure for EGJ tumors has not been standardized. METHODS: Patients with cT2-T4 adenocarcinoma or squamous cell carcinoma located within 2.0 cm of the EGJ were enrolled before surgery. Surgeons dissected all lymph nodes prespecified in the protocol, using either the abdominal transhiatal or right transthoracic approach. The primary endpoint was the metastasis rate of each lymph node. Lymph nodes were classified according to metastasis rate, as follows: category-1 (strongly recommended for dissection), rate more than 10%; category-2 (weakly recommended for dissection), rate from 5% to 10%; and category-3 (not recommended for dissection), rate less than 5%. RESULTS: Between 2014 and 2017, 1065 patients with EGJ tumor were screened, and 371 were enrolled. Among 358 patients who underwent surgical resection, category-1 nodes included abdominal stations 1, 2, 3, 7, 9, and 11p, whereas category-2 nodes included abdominal stations 8a, 19, and lower mediastinal station 110. If esophageal involvement exceeded 2.0 cm, station 110 was assigned to category-1. Among 98 patients who had either adenocarcinoma with esophageal involvement over 3.0 cm or squamous cell carcinoma, there were no category-1 nodes in the upper/middle mediastinal field, whereas category-2 nodes included upper mediastinal station 106recR and middle mediastinal station 108. When esophageal involvement exceeded 4.0 cm, station 106recR was assigned to category-1. CONCLUSION: The study accurately identified the distribution of lymph node metastases from EGJ tumors and the optimal extent of subsequent lymph node dissection.

18.
JAMA Netw Open ; 2(8): e198243, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31373648

RESUMO

Importance: Ramucirumab, a human IgG 1 antibody against vascular endothelial growth factor receptor 2, has been shown to improve progression-free survival and overall survival in patients with advanced gastric cancer in the second-line setting. Objective: To compare progression-free survival for S-1 and oxaliplatin plus ramucirumab with that for S-1 and oxaliplatin plus placebo in patients with advanced gastric cancer. Design, Setting, and Participants: This phase 2, double-blind randomized clinical trial (RAINSTORM [First-line S-1 Plus Oxaliplatin With or Without Ramucirumab Followed by Paclitaxel Plus Ramucirumab in Patients With Advanced Gastric Cancer]) was conducted from October 12, 2015, to April 11, 2018, at 36 sites in Japan, South Korea, and Taiwan. Participants were chemotherapy-naive patients (n = 189) with metastatic gastric or gastroesophageal adenocarcinoma. Analyses of the full analysis set and safety population were conducted between November 27, 2017, and June 4, 2018. Interventions: Patients randomized to the ramucirumab plus S-1 and oxaliplatin arm received S-1, 80 to 120 mg/d twice daily, on days 1 to 14 and oxaliplatin, 100 mg/m2, on day 1 with ramucirumab, 8 mg/kg, on days 1 and 8 in part A (21-day cycle). Patients randomized to the placebo plus S-1 and oxaliplatin arm received the same S-1 and oxaliplatin dosage as well as placebo on days 1 and 8 in part A. Eligible patients received second-line paclitaxel, 80 mg/m2, on days 1, 8, and 15 and ramucirumab, 8 mg/kg, on days 1 and 15 in part B (28-day cycle). Main Outcomes and Measures: The primary end point was progression-free survival, analyzed using the stratified log-rank test; the hazard ratio (HR) was estimated using the stratified Cox proportional hazards regression model. Secondary end points included overall survival and adverse events. Results: In total, 189 patients were randomized and received treatment: 96 to the ramucirumab plus S-1 and oxaliplatin arm and 93 to the placebo plus S-1 and oxaliplatin arm. Among the 189 patients, 121 (64.0%) were male, and the median (range) age was 62.0 (26-84) years. Median progression-free survival was not prolonged in the ramucirumab plus S-1 and oxaliplatin arm compared with the placebo plus S-1 and oxaliplatin arm (6.34 [80% CI, 5.65-6.93] vs 6.74 [80% CI, 5.75-7.13] months; HR, 1.07; 80% CI, 0.86-1.33; P = .70). Median overall survival was 14.65 (80% CI, 12.39-15.67) months in the ramucirumab plus S-1 and oxaliplatin arm and 14.26 (80% CI, 13.83-17.31) months in the placebo plus S-1 and oxaliplatin arm (HR, 1.11; 80% CI, 0.89-1.40; P = .55). The most commonly reported grade 3 or higher treatment-emergent adverse events in the ramucirumab plus S-1 and oxaliplatin arm in part A were decreased neutrophil count (14 patients [14.6%]), hypertension (10 patients [10.4%]), and anemia (10 patients [10.4%]). Conclusions and Relevance: In this randomized clinical trial, the addition of ramucirumab to first-line S-1 and oxaliplatin treatment did not prolong progression-free survival or overall survival compared with S-1 and oxaliplatin alone among East Asian patients with advanced gastric cancer; no new safety signals for ramucirumab were identified. Trial Registration: ClinicalTrials.gov identifier: NCT02539225.

19.
Asian J Endosc Surg ; 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31297969

RESUMO

INTRODUCTION: We propose a novel technique to close Petersen's defect using barbed sutures and evaluate the safety and usefulness of this technique by assessing postoperative complications and measuring the time required to close Petersen's defect. MATERIALS AND SURGICAL TECHNIQUE: Petersen's defect was closed laparoscopically with running non-absorbable barbed sutures (V-loc®) after a nodal dissection and reconstruction procedure. First, the transverse colon was elevated cranially, making the dorsal side of the transverse mesocolon a flattened surface. The intersection of the transverse mesocolon and Roux limb mesentery was then identified, and closure was started from this point. We continued to sew the transverse mesocolon and Roux limb mesentery toward the transverse colon with a running suture. At the end of suturing, we placed one or two stitches in the fatty appendices of the transverse colon and cut the free tail of thread as short as possible. DISCUSSION: We investigated postoperative complications and measured the time required to close Petersen's defect in 64 patients who underwent this technique. The results showed that this closure technique could be performed promptly and safely regardless of the patient, surgical procedure, and the experience of the operator.

20.
J Cancer ; 10(11): 2450-2456, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31258750

RESUMO

Aims: We previously demonstrated that a loss of lean body mass loss at one month after gastrectomy was an independent risk factor for the continuation of adjuvant chemotherapy with S-1. However, it is unclear whether or not lean body mass loss after gastrectomy leads to a poor survival through poor compliance to adjuvant chemotherapy with S-1. Methods: The recurrence free survival (RFS) overall survival (OS) and were examined in 115 patients who underwent curative gastrectomy and were pathologically diagnosed with stage II or III gastric cancer and who received postoperative adjuvant chemotherapy with S-1 between May 2011 and September 2016. Results: The median follow-up period was 40.6 months. The RFS rates at 5 years after surgery were 57.8% in the lean body mass loss ≥5% group and 73.5% in the lean body mass loss <5% group. The univariate and multivariate analyses for the disease free survival (RFS) demonstrated that a lean body mass loss >5% was a significant risk factor. The OS rates at 5 years after surgery were 72.0% in the lean body mass loss ≥5% group and 77.3% in the lean body mass loss <5% group. The OS was slightly worse in the lean body mass loss ≥5% group than in the lean body mass loss <5% group (p=0.2062). Conclusions: The lean body mass loss at one month, which is closely associated with poor S-1 compliance, was an important risk factor for the RFS. A prospective cohort study is necessary to confirm whether or not the lean body mass loss affects the gastric cancer survival.

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