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1.
Anticancer Res ; 42(9): 4545-4552, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36039446

RESUMO

BACKGROUND/AIM: Preoperative sarcopenia is associated with various cancers and affects the long-term prognosis of patients. After gastrectomy for gastric cancer, dynamic changes in body composition occur, and sarcopenia becomes more apparent after surgery than before surgery. However, the relationship between sarcopenia in the early postoperative period and long-term survival is not fully understood. The aim of this study was to determine the effects of surgical sarcopenia on long-term outcomes of patents with gastric cancer. PATIENTS AND METHODS: We included 408 patients who underwent curative gastrectomy (distal or total gastrectomy) for gastric cancer at the Kanagawa Cancer Center from December 2013 to November 2017. Sarcopenia was defined using the skeletal muscle index (SMI), using computed tomography (CT) one month after gastrectomy. We compared the long-term outcomes between patients with and without sarcopenia. RESULTS: The 5-year overall survival (OS) rates were 83.2% and 91.4% in the surgical and non-surgical sarcopenia groups, respectively. The hazard ratio (HR) of surgical sarcopenia for OS was 2.410 (95% confidence interval (CI)=1.321-4.396). In addition, surgical sarcopenia was associated with non-cancer-related deaths and deaths from other cancers. CONCLUSION: Patients with surgical sarcopenia after gastrectomy should be carefully monitored not only for gastric cancer recurrence but also for the occurrence of other diseases, including other cancers.


Assuntos
Sarcopenia , Neoplasias Gástricas , Gastrectomia/efeitos adversos , Humanos , Músculo Esquelético/patologia , Recidiva Local de Neoplasia/patologia , Complicações Pós-Operatórias/patologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Sarcopenia/complicações , Sarcopenia/epidemiologia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/cirurgia
2.
Am J Surg Pathol ; 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35968980

RESUMO

Gastric foveolar-type adenoma (FA) is a rare benign neoplasm occurring either sporadically or in patients with familial adenomatous polyposis (FAP). However, the molecular features of FA and the relationship between sporadic and syndromic lesions remain unclear. In this study, we performed clinicopathological, immunohistochemical, and genetic analyses of 18 sporadic and 30 FAP-associated FAs. Most sporadic and FAP-associated FAs were located in the upper or middle third of the stomach, on a background of fundic gland mucosa. Most lesions were low-grade, but 3 lesions had a high-grade component. Sporadic FAs included 2 morphologically distinct subtypes, that is, flat and raspberry-like FAs, which we distinguished based on the endoscopic features. Seven lesions were regarded as flat FAs, appearing as large, slightly elevated lesions and measuring 11 to 87 mm in size. Conversely, 10 raspberry-like FAs were small bright-red polyps, measuring 2 to 8 mm in size. FAP-associated FAs, particularly larger lesions, exhibited morphologic features resembling flat FAs but varied significantly in size (2 to 103 mm). Mutation analysis identified APC and KRAS mutations in all flat FAs but never in raspberry-like FAs. Remarkably, somatic APC and KRAS mutations were also detected in 19 (63%) and 27 (90%) of FAP-associated FAs, respectively. This indicates that they are genetically equivalent to sporadic, flat FAs. This study showed that sporadic FA includes at least 2 morphologically and genetically distinct subtypes: flat and raspberry-like FA. Furthermore, flat FA represents a sporadic counterpart of FAP-associated FA.

3.
Oncol Lett ; 23(5): 151, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35836480

RESUMO

Basic and clinical reports have suggested that eicosapentaenoic acid (EPA) exhibits anti-tumor activity. The present study evaluated whether perioperative EPA could improve the survival of patients with localized gastric cancer as a key secondary endpoint of a randomized clinical study. The present study was designed as multicenter, open-label, superiority, randomized trial to confirm the preventive effect of EPA on body weight loss after total gastrectomy for gastric cancer. Eligible patients were randomized to either the standard-diet group (EPA-off group) or EPA-on group by a centralized dynamic method. An EPA-enriched supplement (ProSure®) was given to the EPA-on group in addition to their standard diet. This supplement included 600 kcal with 2.2 g/day of EPA. Among the 126 patients who were randomized, 123 patients (EPA-off group, n=60; EPA-on group, n=63) were examined in the survival analyses. All background factors were well balanced between the two groups. The 3-year and 5-year overall survival rates were 74.6 and 67.8%, respectively, in the EPA-off group, and 77.8 and 76.2% in the EPA-on group. There was no significant difference between the EPA-off and EPA-on groups (hazard ratio, 0.77; P=0.424). In the subgroup analysis, the hazard ratio was 0.39 in patients who received neoadjuvant chemotherapy and 0.57 in patients with nodal metastasis. In conclusion, a clear survival benefit of perioperative EPA was not observed in localized gastric cancer. The value of EPA should be further tested in a future study in patients with unfavorable advanced gastric cancer. Clinical trial number: UMIN000006380; date of registration, September 21, 2011.

4.
Eur J Surg Oncol ; 2022 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-35868951

RESUMO

BACKGROUND: Splenic hilar lymphadenectomy is not recommended for advanced proximal gastric cancer that does not invade the greater curvature according to the results of the previous studies. The efficacy of splenic hilar lymphadenectomy for type II and type III adenocarcinomas of the esophagogastric junction and easy spread to the greater curvature of the stomach remains unclear. This study aimed to investigate the efficacy of splenic hilar lymphadenectomy and identify the risk factors for metastasis to splenic hilar nodes. METHODS: We examined patients who underwent R0/1 gastrectomy for Siewert types II and III at a single high-volume center in Japan. We analyzed the metastatic incidence, therapeutic value index, and risk factors for splenic hilar lymph node metastasis. RESULTS: We examined 126 patients (74, type II; 52, type III). Splenectomy was performed in 76 patients. Metastatic incidence and the therapeutic value index of splenic hilar lymph nodes in patients with type II and type III tumors were 4.5% and 0, and 21.9% and 9.4, respectively. In the patients who underwent splenectomy, we identified Siewert type III tumors (odds ratio: 6.93, 95% confidence interval: 1.24-38.8, p = 0.027) and tumor location other than the lesser curvature (odds ratio: 7.36, 95% confidence interval: 1.32-41.1, p = 0.023) to be independent risk factors. The metastatic incidence (46.2%) and therapeutic value index (15.4) were high in patients with both risk factors. CONCLUSIONS: Splenic hilar lymphadenectomy may contribute to the survival of patients with Siewert type III tumors, especially when the predominant location is not the lesser curvature.

5.
World J Surg ; 46(10): 2433-2439, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35842544

RESUMO

INTRODUCTION: Patients requiring total gastrectomy for gastric cancer experience a decrease in food intake leading to severe body weight loss after surgery. This loss may be prevented using a high-density liquid diet of high caloric content and minimal volume. This phase II study evaluated the feasibility and safety of a high-density liquid diet (UpLead®; Terumo Corporation, Tokyo, Japan) after total gastrectomy. METHODS: UpLead® (1 pack, 100 mL, 400 kcal/day) was administered after surgery for 28 days. The primary endpoint was the % relative dose intensity of 28 days of UpLead intake®. The secondary endpoint was % body weight loss at 1 and 3 months after surgery. The sample size was 35 considering expected and threshold values of 80 and 60%, respectively, with a one-sided alpha error of 10% and statistical power of 80%. RESULTS: Among 35 patients enrolled before surgery between April 2018 and December 2019, 29 patients who could initiate UpLead® after surgery were analyzed. Seven patients had interrupted UpLead® intake due to taste intolerance (n = 6) and due to a duodenal stump fistula (n = 1). The remaining 22 patients completed 28 days of UpLead® intake, including temporary interruption, with no associated adverse events. The median relative dose intensity was 25.8% (95% confidence interval: 20.6-42.0%). The median body weight loss at 1 and 3 months after surgery was 7.2% (range: 3.2-13.9%) and 13.1% (range: 2.5-20.4%), respectively. CONCLUSIONS: Oral nutritional supplementation with a high-density liquid diet (UpLead®) was safely administered but was not feasible after total gastrectomy for gastric cancer. Clinical trial registration number UMIN000032291.


Assuntos
Dieta , Suplementos Nutricionais , Neoplasias Gástricas , Dieta/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Estudos de Viabilidade , Gastrectomia , Humanos , Neoplasias Gástricas/cirurgia , Redução de Peso
6.
Gastric Cancer ; 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35767198

RESUMO

BACKGROUND: The blood concentration of S-1 and adverse events are affected by renal function. Herein, an S-1 dosage formula was developed based on renal function, indicating the dose for a target blood concentration. This study aimed to explore the usefulness of the formula in adjuvant chemotherapy for gastric cancer. METHODS: In this ad hoc analysis of the JCOG1001 trial, which evaluated the role of bursectomy for resectable gastric cancer, the recommended dose of S-1 was calculated using the following formula: 1447.8 × (14.5 + 0.301 × CLcr + 8.23 × SEX [male = 1, female = 0]) × body surface area (BSA) (mg/day). Patients were divided into three groups by comparing the initial S-1 dose determined using BSA with the dose recommended by the formula: underdose (UD), equal dose (ED), and overdose (OD). RESULTS: Among 686 eligible patients, 58, 304, and 324 patients were classified into the UD, ED, and OD groups. The patients' characteristics in the UD/ED/OD groups were median age (53.5/64.0/67.5 years), male sex (98.3%/75.3%/58.0%), and median BMI (24.8/22.8/22.3), respectively. The planned 1-year adjuvant S-1 therapy was completed in 74.1%/73.7%/68.5%, dose reduction was required in 8.6%/21.1%/30.6%, and treatment schedule was altered in 8.6%/17.1/19.8% in the UD/ED/OD groups, resulting in the 5-year overall survival rates of 77.3%/74.3%/77.0%, respectively. The incidences of grade > 3 anemia, thrombocytopenia, diarrhea, stomatitis, and anorexia were significantly higher in the OD group than in the ED and UD groups. CONCLUSIONS: Dose optimization using an S-1 dosage formula can potentially reduce grade ≥ 3 adverse events for overdosed patients.

7.
BMC Surg ; 22(1): 220, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35672847

RESUMO

BACKGROUND: Pneumonia is a major cause of death in the elderly population. Considering body weight loss, muscle loss, and reflux after gastrectomy, elderly patients are considered to be at very high risk for pneumonia, which could decrease overall survival because early gastric cancer is mostly curable only by surgery. We aimed to clarify the incidence of pneumonia in the long-term period after gastrectomy in elderly patients who were diagnosed with early gastric cancer and its risk factors. METHODS: We retrospectively examined patients of > 75 years of age who underwent R0 gastrectomy for gastric cancer and who were diagnosed with T1 disease at National Cancer Center Hospital between 2005 and 2012. Long-term postoperative pneumonia was diagnosed by chest computed tomography every year until 2 years after surgery. The presence of preoperative sarcopenia was assessed using preoperative L3 skeletal muscle index. RESULTS: 167 patients were included in this study. Long-term postoperative pneumonia was observed in 44 (26%) patients. Of the 44 people diagnosed with long-term postoperative pneumonia, 33 were diagnosed in the 1st year and 11 in the 2nd year. 117 patients (70%) were diagnosed with sarcopenia which was significantly frequently found in the patients who developed long-term postoperative pneumonia (91%) than those without (63%). Preoperative sarcopenia was the only independent risk factor in multivariate analysis. Type of gastrectomy was not a significant risk factor. CONCLUSIONS: Long-term postoperative pneumonia was frequently observed in the elderly patients. Preoperative sarcopenia was associated with long-term postoperative pneumonia in elderly patients who underwent curative surgery for gastric cancer. After gastrectomy, long-term special care would be required for elderly patients, especially with sarcopenia.


Assuntos
Pneumonia , Sarcopenia , Neoplasias Gástricas , Idoso , Gastrectomia/efeitos adversos , Humanos , Pneumonia/epidemiologia , Pneumonia/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Sarcopenia/complicações , Sarcopenia/epidemiologia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/cirurgia
9.
Sci Rep ; 12(1): 8509, 2022 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-35595817

RESUMO

Biomarkers for selecting gastric cancer (GC) patients likely to benefit from sequential paclitaxel treatment followed by fluorinated-pyrimidine-based adjuvant chemotherapy (sequential paclitaxel) were investigated using tissue samples of patients recruited into SAMIT, a phase III randomized controlled trial. Total RNA was extracted from 556 GC resection samples. The expression of 105 genes was quantified using real-time PCR. Genes predicting the benefit of sequential paclitaxel on overall survival, disease-free survival, and cumulative incidence of relapse were identified based on the ranking of p-values associated with the interaction between the biomarker and sequential paclitaxel or monotherapy groups. Low VSNL1 and CD44 expression predicted the benefit of sequential paclitaxel treatment for all three endpoints. Patients with combined low expression of both genes benefitted most from sequential paclitaxel therapy (hazard ratio = 0.48 [95% confidence interval, 0.30-0.78]; p < 0.01; interaction p-value < 0.01). This is the first study to identify VSNL1 and CD44 RNA expression levels as biomarkers for selecting GC patients that are likely to benefit from sequential paclitaxel treatment followed by fluorinated-pyrimidine-based adjuvant chemotherapy. Our findings may facilitate clinical trials on biomarker-oriented postoperative adjuvant chemotherapy for patients with locally advanced GC.


Assuntos
Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais/genética , Quimioterapia Adjuvante/efeitos adversos , Intervalo Livre de Doença , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Paclitaxel/uso terapêutico , Pirimidinas/uso terapêutico , RNA , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirurgia
10.
Future Oncol ; 18(20): 2511-2519, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35582901

RESUMO

Background: To improve the diagnostic accuracy of preoperative T staging in gastric cancer, the authors evaluated tumor-related factors that might affect the diagnosis. Materials & methods: The authors analyzed the data of cT2-4b gastric cancer patients enrolled in the prospective, multicenter JCOG1302A study. They used contrast-enhanced computed tomography to analyze the association between tumor-related factors and the diagnostic accuracy of T3-4b staging for gastric cancer. Results: Among 876 cT3-4b tumors, the diagnostic accuracy was relatively low in the lower third of the stomach compared with those in the upper or middle. A multivariable analysis revealed that accuracy was higher in the lesser curvature or entire circumference region than in other areas (p < 0.001), in macroscopic types 3/5 than in types 0/1/2 (p = 0.003) and in the undifferentiated histological type than in the differentiated type (p = 0.011). Conclusion: The authors found tumor-related factors affecting preoperative T staging by enhanced computed tomography.


Additional chemotherapy before surgery is expected to have potentially beneficial effects on prognosis compared with chemotherapy only after surgery for advanced gastric cancer. The consideration of chemotherapy before surgery depends on preoperative diagnosis of the depth of tumor invasion in the stomach wall. Overdiagnosis of the depth of tumor invasion may lead to unnecessary administration of chemotherapy that is harmful to the patient. Tumor-related factors such as tumor location, macroscopic type and histological type may affect the diagnosis. Therefore, these factors should be considered with special care for the diagnosis, which may lead to higher accuracy in diagnosing the depth of tumor invasion in gastric cancer.


Assuntos
Neoplasias Gástricas , Humanos , Estadiamento de Neoplasias , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Tomografia Computadorizada por Raios X/métodos
11.
Eur J Surg Oncol ; 48(8): 1785-1789, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35396146

RESUMO

BACKGROUND: Surgery for T1b gastric cancer requires suprapancreatic nodes (SPA nodes) and perigastric nodes (PG nodes), however, SPA nodal dissection can cause pancreatic complications. If endoscopic treatment followed by additional surgery is planned, it may be possible to predict SPA nodal metastasis by analyzing the pathological information of the primary tumor in addition to the clinical findings. METHODS: Patients who underwent D1+ or D2 and who were pathologically diagnosed with pT1b were retrospectively analyzed. The stations were divided into the nodes located at the perigastric area (PG nodes; #1-7) and the nodes located at the suprapancreatic area (SPA nodes; #8a-12a). The patients were classified into those with and without metastasis to the SPA nodes. Clinicopathological factors were investigated for their possible association with metastasis to the SPA nodes. RESULTS: A total of 2017 patients were examined in this study. Metastasis to the SPA nodes was observed in 80 patients (4%). In a multivariate analysis, undifferentiated histology, lower third, and lymphovascular invasion were independent risk factors for metastasis to the SPA nodes. The risk of metastasis to the SPA nodes was <2% in upper/middle tumors of differentiated type with no lymphovascular invasion and in lower tumors of undifferentiated type with no lymphovascular invasion. On the other hand, the risk of metastasis to the SPA nodes was >10% in lower tumors of undifferentiated type with lymphovascular invasion. CONCLUSION: SPA nodal metastasis can be predicted when endoscopic treatment is initially planned. SPA nodal dissection should not be uniformly selected for T1b gastric cancer.


Assuntos
Neoplasias Gástricas , Gastrectomia , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática/patologia , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
13.
Jpn J Clin Oncol ; 52(5): 417-424, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35246684

RESUMO

Esophagogastric junction cancer is defined as adenocarcinoma with the epicenter within 5 cm of the esophagogastric junction in the West according to the Siewert classification. In contrast, it is defined as cancer of any histological type with the epicenter located within 2 cm proximal or distal to the esophagogastric junction in Japan according to the Nishi classification. Recently, the incidence of esophagogastric junction cancer has been rapidly rising all over the world, leading to much attention. Esophagogastric junction cancer was previously treated like gastric cancer or esophageal cancer because it is a less frequently occurring tumor. Esophagogastric junction cancer is considered to have worse prognosis than gastric cancer. Therefore, in recent years, esophagogastric junction cancer has been recognized as an independent malignant disease with poor prognosis, and thus development of treatment strategies focused on esophagogastric junction cancer is needed. The mapping of frequent metastasis in the mediastinal and abdominal lymph nodes has revealed the lymphatic flow from esophagogastric junction cancer specifically, establishing the optimal lymph node dissection area and surgical approach. The development of multimodal treatment that includes chemotherapy, radiotherapy and immunotherapy has been applied to improve the survival of esophagogastric junction cancer. In this review, we summarize clinical trials with important evidence on surgical and multimodal perioperative treatments for esophagogastric junction cancer.


Assuntos
Neoplasias Esofágicas , Neoplasias Gástricas , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Junção Esofagogástrica/patologia , Junção Esofagogástrica/cirurgia , Gastrectomia , Humanos , Excisão de Linfonodo , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
14.
Gastric Cancer ; 25(3): 619-628, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35254550

RESUMO

BACKGROUND: Nivolumab monotherapy has demonstrated superior efficacy in advanced unresectable gastric cancer (GC), but its impact on resectable GC remains unknown. This phase I study aimed to evaluate safety, feasibility, and potential biomarkers of neoadjuvant nivolumab monotherapy in resectable GC. METHODS: Untreated, resectable, cT2 or more advanced gastric adenocarcinomas with clinical stage I, II, or III were treated with two doses of nivolumab before gastrectomy. Patients were excluded if their tumors may be applicable to neoadjuvant chemotherapy. The primary endpoint was the incidence of adverse event (AE) categories of special interest. RESULTS: All of the 31 enrolled patients completed 2 doses of nivolumab monotherapy. While 30 (97%) patients underwent surgery with curative intent, 1 patient discontinued before the planned surgical intervention because of a newly emerging liver metastasis. Seven patients (23%) had nivolumab treatment-related AEs, and one patient had a treatment-related AE of grade 3-4. The incidences of treatment-related AE categories of special interest ranged from 0 to 6%. Notable surgical complications included two cases of grade 3 anastomotic leakage and two cases of pancreatic fistula. The major pathologic response (MPR) assessed by the independent pathology review committee was achieved in five (16%) patients, of which one patient had a pathologic complete response. The MPR was mostly observed in patients with positive PD-L1 expression, high microsatellite instability, and/or high tumor mutation burden. CONCLUSIONS: Neoadjuvant nivolumab monotherapy is feasible with an acceptable safety profile and induces a MPR in certain patients with resectable GC. (Registration: clinicaltrials.jp, JapicCTI-183895).


Assuntos
Adenocarcinoma , Nivolumabe , Neoplasias Gástricas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Humanos , Instabilidade de Microssatélites , Terapia Neoadjuvante/efeitos adversos , Nivolumabe/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia
15.
Br J Surg ; 109(3): 291-297, 2022 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-35179206

RESUMO

BACKGROUND: Patients with Epstein-Barr virus-positive gastric cancers or those with microsatellite instability appear to have a favourable prognosis. However, the prognostic value of the chromosomal status (chromosome-stable (CS) versus chromosomal instable (CIN)) remains unclear in gastric cancer. METHODS: Gene copy number aberrations (CNAs) were determined in 16 CIN-associated genes in a retrospective study including test and validation cohorts of patients with gastric cancer. Patients were stratified into CS (no CNA), CINlow (1-2 CNAs) or CINhigh (3 or more CNAs). The relationship between chromosomal status, clinicopathological variables, and overall survival (OS) was analysed. The relationship between chromosomal status, p53 expression, and tumour infiltrating immune cells was also assessed and validated externally. RESULTS: The test and validation cohorts included 206 and 748 patients, respectively. CINlow and CINhigh were seen in 35.0 and 15.0 per cent of patients, respectively, in the test cohort, and 48.5 and 20.7 per cent in the validation cohort. Patients with CINhigh gastric cancer had the poorest OS in the test and validation cohorts. In multivariable analysis, CINlow, CINhigh and pTNM stage III-IV (P < 0.001) were independently associated with poor OS. CIN was associated with high p53 expression and low immune cell infiltration. CONCLUSION: CIN may be a potential new prognostic biomarker independent of pTNM stage in gastric cancer. Patients with gastric cancer demonstrating CIN appear to be immunosuppressed, which might represent one of the underlying mechanisms explaining the poor survival and may help guide future therapeutic decisions.


Assuntos
Adenocarcinoma/genética , Adenocarcinoma/imunologia , Instabilidade Cromossômica , Dosagem de Genes , Hospedeiro Imunocomprometido , Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologia , Adenocarcinoma/patologia , Adenocarcinoma/virologia , Idoso , Biomarcadores Tumorais/genética , Feminino , Genes p53/genética , Herpesvirus Humano 4/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/virologia
16.
J Gastroenterol ; 57(5): 333-343, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35188590

RESUMO

BACKGROUND: The heterotopic submucosal gland (HSG) is a common incidental finding in gastrectomy specimens. The majority of HSGs are small incidental lesions, which are also known as gastritis cystica profunda. However, larger lesions may appear as an inverted growth of well-organized mucosa referred to as gastric inverted polyps. METHODS: To determine whether genetic alterations are involved in HSG development, we analyzed 63 gastric HSG lesions using targeted next-generation sequencing and immunohistochemistry. RESULTS: Histologically, HSG lesions consistently had areas of pyloric gland differentiation with variable extent of foveolar differentiation. Although the background mucosa showed intestinal metaplasia in most cases (98%), intestinal-type epithelium was seen in only one HSG lesion (2%). Sequencing analysis identified activating KRAS, BRAF, CTNNB1, and GNAS mutations in 34 (54%), 1 (2%), 1 (2%), and 7 (11%) lesions, respectively. HSG lesions harboring a KRAS mutation were more likely to present extensive foveolar differentiation (P = 0.013) and absence of parietal cells (P = 0.0081). Five HSG lesions had a dysplastic component, and concordant genetic alterations were detected between the non-dysplastic and dysplastic areas of two lesions that were successfully analyzed. Immunohistochemical staining demonstrated diffuse expression of mutant KRAS protein in lesions with the most common genetic alteration, KRAS G12D. CONCLUSIONS: Our study demonstrated that a major proportion of HSGs were proliferative lesions associated with oncogenic mutations, with more than half of lesions harboring activating KRAS mutations.


Assuntos
Proteínas Proto-Oncogênicas p21(ras) , Neoplasias Gástricas , Pólipos Adenomatosos , Cromograninas/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Humanos , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Gástricas/patologia
17.
Cancer Lett ; 532: 215587, 2022 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-35131383

RESUMO

The CpG island methylator phenotype (CIMP) is associated with prognosis and drug sensitivity in multiple cancer types. In gastric cancer, the CIMP is closely associated with Epstein-Barr virus (EBV) infection and AT-rich interactive domain 1A (ARID1A) mutations, a component of the SWI/SNF chromatin remodeling complex. However, the involvement of SWI/SNF defects in CIMP induction has been unclear. In this study, we demonstrate a causal role of ARID1A loss-of-function in CIMP induction. Mutations of SWI/SNF components, especially ARID1A, was associated with the CIMP, as well as EBV infection, in gastric cancers, and also in uterine endometrial and colorectal cancers, which are not affected by EBV infection. Genome-wide DNA methylation analysis showed that ARID1A knockout (KO) in cultured 293FT cells and gastric epithelial cells, GES1, induced aberrant DNA methylation of a substantial number of CpG sites. DNA methylation was induced at genomic regions with high levels of pre-existing histone H3 lysine 27 trimethylation (H3K27me3) and those with acquired H3K27me3 by ARID1A KO. These results showed that the ARID1A mutation induced aberrant DNA methylation, and this is likely to be one of the potential mechanisms of CIMP induction.


Assuntos
Neoplasias Colorretais , Infecções por Vírus Epstein-Barr , Neoplasias Gástricas , Neoplasias Colorretais/genética , Ilhas de CpG , Metilação de DNA , Proteínas de Ligação a DNA/genética , Infecções por Vírus Epstein-Barr/genética , Herpesvirus Humano 4/genética , Histonas/genética , Humanos , Fenótipo , Neoplasias Gástricas/genética , Fatores de Transcrição/genética
18.
Eur J Surg Oncol ; 48(8): 1753-1759, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35082047

RESUMO

BACKGROUND: Indications for adjuvant chemotherapy for advanced gastric cancer are determined based on the pathological diagnosis. However, macroscopic diagnoses have been reported as predictors of peritoneal recurrence and survival. This study investigated the predictability of peritoneal recurrence and survival based on macroscopically (sT) and pathologically (pT) diagnosed serosal invasion to identify more sensitive predictors of peritoneal recurrence. METHODS: This study included 396 patients who underwent R0 resection without adjuvant chemotherapy with S-1 in the JCOG0110 study. Tumor depth limited to the subserosa (SS) was defined as serosal invasion negative (T-), while tumors with serosal invasion (SE, SI) were defined as serosal invasion positive (T+). The predictability of peritoneal recurrence based on sT and pT was evaluated using the Fine and Gray model. Cox regression analyses were performed for overall survival (OS) and relapse-free survival (RFS) with sT or pT as covariates. FINDINGS: A total of 150 patients (37.9%) were sT+ and 82 (26.3%) were pT+. Sixty-two patients (15.7%) were sT+/pT+, 88 (22.2%) were sT+/pT-, 20 (5.1%) were sT-/pT+, and 226 (57.1%) were sT-/pT-. Both sT and pT were found to be independent predictors of peritoneal recurrence, OS, and RFS. The 5-year RFS rates of sT+/pT+, sT+/pT-, sT-/pT+, and sT-/pT-patients were 45.2%, 63.6%, 55.0%, and 81.8%, respectively. CONCLUSION: Intraoperatively diagnosed macroscopic serosal invasion showed a similar predictive value for peritoneal recurrence as pathologically diagnosed serosal invasion. The establishment of a novel staging system incorporating macroscopic serosal invasion is recommended.


Assuntos
Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Membrana Serosa/patologia , Neoplasias Gástricas/patologia
19.
Eur J Surg Oncol ; 48(3): 597-603, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35031158

RESUMO

BACKGROUND: There is no consensus on the extent of nodal dissection for duodenal bulbar NENs (neuroendocrine neoplasms). MATERIALS AND METHODS: We constructed and analyzed a combined dataset consisting of the patients who received surgery in our hospital and the patients from the literature based on a systematic review. The incidence, risk factors and location of nodal metastases were examined. RESULTS: Fifty-nine cases including 11 cases managed at our hospital and 48 cases identified from the literature search were examined. Nodal metastasis was observed in 24 patients (40.7%). The 5-year overall survival rate was 100%, regardless of nodal metastasis. Risk factors for lymph node metastasis were tumor size ≥15 mm and muscularis propria or deeper invasion. Stomach-related lymph node metastasis was found in >20% of patients who were positive for at least one risk factor and 15.4% when patients were negative for both risk factors, while pancreas-related lymph node metastasis was observed in 45.5% of patients who were positive for both risk factors, 7.7% who were only positive for one risk factor, and 0% who were negative for both risk factors. CONCLUSIONS: Tumor size and depth of invasion would determine whether the optimal surgery for duodenal bulbar NENs is distal gastrectomy or pancreatico-duodenectomy.


Assuntos
Neoplasias Duodenais , Tumores Neuroendócrinos , Neoplasias Gástricas , Dissecação , Neoplasias Duodenais/patologia , Neoplasias Duodenais/cirurgia , Gastrectomia , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática/patologia , Tumores Neuroendócrinos/patologia , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
20.
Surg Today ; 52(2): 231-238, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34286401

RESUMO

PURPOSES: The spread of coronavirus disease 2019 (COVID-19) has affected socioeconomic and healthcare systems in many countries. Accordingly, many individuals may have canceled their annual health-check programs, including esophagogastroduodenoscopy, which would have resulted in lower numbers of newly diagnosed patients with gastric cancer in comparison to other times. METHODS: Questionnaires were distributed to 62 hospitals every week from May 2020 to August 2020 (total 744) through mailing lists of the Stomach Cancer Study Group of the Japan Clinical Oncology Group. The number of patients with gastric cancer and hospital systems during the COVID-19 pandemic were surveyed. RESULTS: In total, 74% (551 out of 744) of the questionnaires were answered and analyzed. In early May, approximately 50% of hospitals had to restrict surgical slots due to the COVID-19 pandemic. However, they gradually loosened the restrictions thereafter. The number of gastrectomies was < 80% that of the same period in the previous year, and hospitals in Tokyo were seriously affected by a 50% decrease in the number of gastrectomies. CONCLUSIONS: The number of gastrectomies was lower than that in the previous year. Further multi-center follow-up studies are required to evaluate the long-term effects of COVID-19 on the clinical outcomes of patients with gastric cancer.


Assuntos
COVID-19/epidemiologia , Atenção à Saúde/organização & administração , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Controle de Infecções/organização & administração , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia , COVID-19/prevenção & controle , COVID-19/transmissão , Endoscopia do Sistema Digestório/estatística & dados numéricos , Utilização de Instalações e Serviços , Gastrectomia/estatística & dados numéricos , Humanos , Japão , Utilização de Procedimentos e Técnicas , Neoplasias Gástricas/epidemiologia , Inquéritos e Questionários
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