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1.
Int J Clin Oncol ; 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32124094

RESUMO

BACKGROUND: The optimal dose of each drug used in the docetaxel, oxaliplatin, and S-1 (DOS) chemotherapy remains to be clarified for the Japanese population. The purpose of this study was to determine a recommended dose for a combination neoadjuvant DOS chemotherapy for Japanese patients with locally advanced adenocarcinoma of the esophagogastric junction (AEG). METHODS: Patients with cT3 or more advanced AEG without distant metastasis were eligible for this study. The planned dosages of docetaxel (mg/m2, day 1), oxaliplatin (mg/m2, day 1), and S-1 (mg/day, days 1-14) were: 50/100/80-120 at level 1, and 60/100/80-120 at level 2, respectively. The treatment cycle was repeated every 3 weeks, and patients were assessed for response to the treatment after 2 and 3 cycles. This study was registered in the UMIN Clinical Trial Registry (UMIN 000022210). RESULTS: We enrolled 12 patients with locally advanced AEG in this study. At dose level 1, one of the six patients experienced dose-limiting toxicity (DLT) of grade 3 diarrhea and grade 3 febrile neutropenia. Two of the next six patients also experienced DLT of need for more than 2-week delay of the start of the second cycle due to adverse events at dose level 2. Based on these results, level 2 was considered the recommended dose for this regimen. CONCLUSION: Recommended doses of docetaxel (mg/m2), oxaliplatin (mg/m2), and S-1 (mg/day) were 60/100/80-120. This chemotherapy scheme showed good preliminary efficacy with acceptable toxicity warranting a further phase II trial to investigate the efficacy of this regimen.

2.
J Surg Res ; 245: 552-563, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31472311

RESUMO

BACKGROUND: It is elusive which subtypes of immune cells are pivotal in cancer progression and prognosis in gastric cancer (GC). The aim of this study is to clarify clinical impact of immature myeloid-derived immune cells in patients with GC who underwent curative gastrectomy with curative lymphadenectomy and treated with S-1 (tegafur/gimeracil/oteracil) postoperatively. METHODS: The prognostic impact of recruited CD33+ immature myeloid-derived cells were clinicopathologically analyzed in curatively resected stage II and III GC. Correlation of preoperative peripheral leukocyte fractions with recruited CD33+ immature cells was also assessed. RESULTS: Patients with high CD33+ cell counts in primary tumor showed dramatically worse prognosis (5-y recurrence-free survival 29.0%) than that of the counterparts (79.4%). High CD33+ cell counts independently predicted poor prognosis in stage II/III (hazard ratio, 4.34; P < 0.001). In analyses of each stage, high CD33+ cell count was pivotally associated with poor prognosis in both stages. There was no significant correlation of each peripheral leukocyte fraction with CD33+ cell recruitment. Of note, high CD33+ cell count was significantly correlated with hematogenous recurrence. CONCLUSIONS: Recruitment of CD33+ immature myeloid cells critically predict hematogenous recurrences in curatively resected advanced GC. These results give rational to focusing on CD33+ myeloid-derived cells as a novel approach to tackle advanced GC.


Assuntos
Células Supressoras Mieloides/imunologia , Recidiva Local de Neoplasia/diagnóstico , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo , Neoplasias Gástricas/terapia , Estômago/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimioterapia Adjuvante/métodos , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Gastrectomia , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Células Supressoras Mieloides/metabolismo , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/imunologia , Estadiamento de Neoplasias , Ácido Oxônico/administração & dosagem , Prognóstico , Estômago/citologia , Estômago/cirurgia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia , Tegafur/administração & dosagem
3.
Asian J Endosc Surg ; 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31814306

RESUMO

INTRODUCTION: The aim of this study is to evaluate the efficacy of delta-shaped anastomosis compared to circular stapler anastomosis in laparoscopic distal gastrectomy with Billroth I reconstruction. METHODS: This is a single-center randomized controlled study. Eligibility criteria included histologically proven gastric adenocarcinoma in the lower third of the stomach, clinical stage I tumor. Patients were preoperatively randomized to circular stapler anastomosis or delta-shaped anastomosis. The primary endpoint is the number of analgesics used during three days after surgery. We compared the surgical outcomes of the two groups. Postoperative quality of life was evaluated using the Postgastrectomy Syndrome Assessment Scale-45. This trial was registered at the UMIN Clinical Trials Registry as UMIN000025160. RESULTS: Between December 2016 and September 2018, 39 patients (delta-shaped anastomosis 18, circular stapler anastomosis 21) were enrolled. There was no difference in the number of analgesics used during three days after surgery (median nine: delta-shaped anastomosis vs nine: circular stapler anastomosis, P = .91). There was no difference in the overall proportion with in-hospital grade II-IIIB surgical complications (11%: delta-shaped anastomosis, 14%: circular stapler anastomosis). There was no operation-related death in either arm. Regarding postoperative quality of life evaluated one month after surgery, diarrhea subscale was significantly worse in delta-shaped anastomosis than in circular stapler anastomosis. CONCLUSION: We did not demonstrate the advantage of delta-shaped anastomosis in terms of postoperative pain. Since delta-shaped anastomosis tended to cause postoperative abdominal symptoms related to diarrhea, we should carefully apply the delta-shaped anastomosis to laparoscopic distal gastrectomy with Billroth I reconstruction.

4.
Ann Surg Oncol ; 26(13): 4814-4825, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31529309

RESUMO

BACKGROUND: OBP-801 is a novel histone deacetylase inhibitor being developed as an anticancer drug. In this study, we explored genes to predict drug resistance in human cancer. METHODS: OBP-801 resistance was assessed in 37 strains of human cancer cell lines. Expression microarrays harboring 54,675 genes were used to focus on candidate genes, which were validated for both functional and clinical relevance in esophageal squamous cell carcinoma (ESCC). RESULTS: OBP-801 is sensitive to esophageal, gastric, and thyroid cancer, and resistant to some esophageal and colorectal cancers. We therefore used ESCC to explore genes. Comprehensive exploration focused on ΔNp63/SOX2, which were both genetically and epigenetically overexpressed in ESCC. Genomic amplifications of ΔNp63/SOX2 were tightly correlated each other (r = 0.81). Importantly, genomic amplification of ΔNp63/SOX2 in the resected tumors after neoadjuvant chemotherapy was significantly associated with histological grade of response (G1). Forced expression of either of these two genes did not induce each other, suggesting that their functional relevances were independent and showed robust drug resistance in OBP-801, as well as 5-fluorouracil. Furthermore, ΔNp63 could exert a potent oncogenic potential. RNA interference of ΔNp63 supported its oncological properties, as well as drug resistance. CONCLUSION: Comprehensive exploration of genes involved in anticancer drug residence could identify critical oncogenes of ΔNp63/SOX2 that would predict chemotherapy response in ESCC.

5.
Esophagus ; 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31321580

RESUMO

BACKGROUND: Standard treatment for resectable small cell neuroendocrine carcinoma of the esophagus (SCNEC-E) remains to be established. METHODS: We retrospectively studied 7 consecutive patients with resectable SCNEC-E who received definitive chemoradiotherapy (dCRT) to evaluate the safety and efficacy. Treatment consisted of two courses of chemotherapy with cisplatin (80 mg/m2 on day 1) and etoposide (100 mg/m2 on days 1-3) or carboplatin (AUC 5 on day 1) and etoposide (80 mg/m2 on days 1-3) given every 4 weeks during dCRT. The total radiation dose was 50.4 Gy (28 fractions). RESULTS: The clinical stage was IA in 1 patient, IB in 2 patients, IIA in 3 patients, and IIB in 1 patient. Definitive CRT was completed in all patients. The median overall treatment time of radiotherapy was 44 days. The chemotherapy regimen included in dCRT was cisplatin and etoposide in 3 patients and carboplatin and etoposide in 4 patients. Acute adverse events of grade 3 or 4 were neutropenia 100%, thrombocytopenia 43%, febrile neutropenia 43%, and nausea 14%. There were no late grade 3 or 4 adverse events. The median survival time was 32 months. The complete response rate was 100%. The recurrence rate was 43%. The median survival of the 4 patients without recurrence was 56 months. CONCLUSIONS: Definitive CRT with cisplatin and etoposide or carboplatin and etoposide is a feasible treatment for the resectable SCNEC-E, and long-term survival can be achieved in some patients.

6.
Oncotarget ; 10(25): 2423-2434, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-31069006

RESUMO

Background: Early detection of remnant gastric cancer (RGC) is required to reduce the risk of death, but long-term endoscopic surveillance is difficult after gastrectomy. In this study, data for the methylation status of 4 methylation genes (CDO1, HOPX, Reprimo, and E-cadherin) to predict the onset of RGC are presented. Results: The 4 genes showed hypermethylation in RGC tumors in contrast to the corresponding non-cancerous mucosa tissues. The methylation level in the non-cancerous mucosa tissues of the initial surgery was obviously high in initial malignant disease for CDO1 (P = 0.0001), while in initial benign one for E-cadherin (P = 0.003). Promoter DNA methylation status in the remnant non-cancerous mucosa tissues together with the basic clinical data in turn predicted either initial malignant disease or initial benign disease with a high AUC score of 0.94, suggesting that methylation events are differentially recognized between the initial malignant and benign disease. We then finally confirmed that 4 genes hypermethylation of the non-cancerous tissues by biopsy prior to onset of RGC could predict terms until RGC occurred (P < 0.0001). Methods: A total of 58 RGC patients were used to establish the model. The 4 genes promoter methylation were analyzed for DNA obtained from the patient's specimens using quantitative methylation specific polymerase chain reaction. Conclusions: This risk model would help provide guidance for endoscopic surveillance plan of RGC after gastrectomy.

7.
PLoS One ; 14(4): e0214872, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30934021

RESUMO

BACKGROUND: There have been few available prognostic biomarkers in gastric cancer. We rigorously assessed the clinical relevance of promoter DNA methylation of Cysteine dioxygenase type 1 (CDO1) gene, a cancer-specific aberration, in human gastric cancer. METHODS: Quantitative CDO1 methylation value (TaqMeth V) was initially calculated in 138 gastric cancer patients operated in 2005, and its clinical significance was elucidated. As a subsequent expanded set, 154 gastric cancer patients with pathological stage (pStage) II / III with no postoperative therapy were validated between 2000 and 2010. RESULTS: (1) Median TaqMeth V of CDO1 gene methylation of gastric cancer was 25.6, ranging from 0 to 120.9. As pStage progressed, CDO1 TaqMeth V became higher (p < 0.0001). (2) The optimal cut-off value was determined to be 32.6; gastric cancer patients with high CDO1 gene methylation showed a significantly worse prognosis than those with low CDO1 gene methylation (p < 0.0001). (3) A multivariate cox proportional hazards model identified high CDO1 gene methylation (p = 0.033) as an independent prognostic factor. (4) The results were recapitulated in the expanded set in pStage III, where high CDO1 gene methylation group had a significantly worse prognosis than low CDO1 gene methylation group (p = 0.0065). Hematogenous metastasis was unique in pStage III with high CDO1 gene methylation (p = 0.0075). (5) Anchorage independent growth was reduced in several gastric cancer cell lines due to forced expression of the CDO1 gene, suggesting that abnormal CDO1 gene expression may represent distant metastatic ability. CONCLUSIONS: Promoter DNA hypermethylation of CDO1 gene was rigorously validated as an important prognostic biomarker in primary gastric cancer with specific stage.


Assuntos
Biomarcadores Tumorais/genética , Cisteína Dioxigenase/genética , Neoplasias Gástricas/genética , Idoso , Linhagem Celular Tumoral , Metilação de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Regiões Promotoras Genéticas , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/patologia , Transfecção
8.
Ann Gastroenterol Surg ; 3(2): 122-129, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30923781

RESUMO

Pathological outcomes are definitely the most important prognostic factors in gastric cancer, but they can be obtained only after surgical resection. Use of preoperative adjuvant chemotherapy is becoming widespread for aggressive human cancer, so clinical factors such as macroscopic features are important as they are highly predictive for patient prognosis. In gastric cancer, the macroscopic type represents a distinct prognosis; Type 0 represents early gastric cancer with excellent prognosis, but, among advanced tumors, giant Type III and Type IV tumors have a dismal prognosis. Japan Clinical Oncology Group (JCOG) Stomach Cancer Study Group adopted macroscopic features as high-risk entities in clinical trials. It makes sense for risk classification to use macroscopic phenotypes because The Cancer Genome Atlas (TCGA) Network has lately subcategorized different histologies associated with specific macroscopic types by the molecular features of the whole genome. Dismal prognosis of Type IV gastric cancer is notorious, but similar prognosis was seen in giant Type III gastric cancer defined as 8 cm or beyond, both of which are unique for their propensity of peritoneal dissemination. In this review, clinical relevance including prognosis of such macroscopic high-risk features will be separately debated in the context of precision medicine and updated prognostic outcomes will be presented under the present standard therapy of curative surgery followed by postoperative S-1 chemotherapy. Moreover, promising emerging novel therapeutic strategies including trimodal potent regimens or intraperitoneal chemotherapy will be described for such aggressive gastric cancer.

9.
J Surg Res ; 238: 224-231, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30772681

RESUMO

BACKGROUND: Conventional laparoscopic and open distal gastrectomy procedures have inherent limitations such as restricted movement of straight forceps and tremor of the tip of the devices that can potentially be overcome using robotic distal gastrectomy (RDG). This single-institutional phase II trial aimed to evaluate the safety and feasibility of RDG with lymph node dissection for clinical stage IA gastric cancer. METHODS: The study included patients with clinical stage IA gastric cancer in the lower two-thirds of the stomach considered to be curatively resected via distal gastrectomy. The primary end point was the proportion of patients who developed intra-abdominal complications, requiring medical or interventional treatment. The planned sample size was 25, calculated based on an expected complication rate of 3% and a threshold complication rate of 15%, with a one-sided alpha of 10%, power of 70%. RESULTS: Overall postoperative complications rate was 16%. The proportion of patients who developed intra-abdominal complications, requiring treatment was 0% (90% confidence interval, 0-9.8%). No patient developed in-hospital adverse events of grade 3 or higher. The short-term clinical outcomes were as follows: the median duration of postoperative hospital stay was 7 d, and 10 patients (40.0%) had a body temperature of 38°C or higher during their hospital stay. CONCLUSIONS: This trial confirmed the safety of RDG with limitation by the restriction of dedicated surgeons. A phase III trial to confirm the superiority of RDG to conventional laparoscopic distal gastrectomy is warranted.


Assuntos
Gastrectomia/efeitos adversos , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Gastrectomia/métodos , Humanos , Incidência , Laparoscopia/métodos , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/métodos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Gástricas/patologia , Resultado do Tratamento
10.
Ann Surg Oncol ; 26(4): 996-1004, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30737666

RESUMO

PURPOSE: The aim of this study is to elucidate the optimized lymph node dissection range in middle thoracic (Mt) esophageal squamous cell carcinoma (ESCC) requiring surgery. PATIENTS AND METHODS: We retrospectively analyzed 165 ESCC patients who underwent surgery with curative intent between 2009 and 2016, including 99 (60%) with MtESCC. Preoperative chemotherapy was administered in more than 80% of cStage II/III MtESCC patients. The rates of pathological and potential metastasis (representing recurrences) to lymph nodes and prognosis (median follow-up 52 months) were clarified. Lymph node dissection efficacy was assessed by calculating the efficacy index (EI) for each lymph node. RESULTS: No. 2R had the highest rate of metastasis, with frequencies of 13/38/46% in cStage I/II/III, respectively, with the highest EI in MtESCC. Recurrences were seen in about 2-10% in the regional (nos. 1, 2L, 4R, and 10) and extraregional lymph nodes (paraaortic lymph node). The EI of lymph nodes was found to exhibit the highest score of 15 for no. 2R, followed by 11.5 for no. 17. The 5-year overall survival (OS) in MtESCC patients who underwent no. 2R lymph node dissection was 73.8%, while those who did not undergo no. 2R dissection did never reach 5-year OS (P = 0.002). CONCLUSIONS: Meticulous lymph node dissection of no. 2R is the most important for long-term survival, and mandatory with the highest priority in MtESCC.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/mortalidade , Excisão de Linfonodo/mortalidade , Recidiva Local de Neoplasia/cirurgia , Neoplasias Torácicas/cirurgia , Idoso , Carcinoma de Células Escamosas/secundário , Progressão da Doença , Neoplasias Esofágicas/patologia , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias Torácicas/patologia
11.
Oncol Lett ; 17(1): 578-586, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30655804

RESUMO

Esophageal carcinosarcoma (ECS) has been suggested to result from an epithelial mesenchymal transition (EMT) phenomenon. However, knowledge on its underlying molecular features is limited. The clinical and pathological features, and the prognosis of ECS require further investigation. In the present study, a total of 325 patients with esophageal tumors were observed between January 2004 and December 2014, of which 6 patients were diagnosed pathologically with ECS. The clinicopathological features were compared with those of corresponding cases with the identical pathological T stage (pT) of esophageal squamous cell carcinoma (ESCC). In terms of the clinical T stage (cT), the 6 cases were composed of cT1, cT2, cT3 and cT4 in 1, 1, 3 and 1 case, respectively. Nevertheless, pT was eventually diagnosed as pT1 in all cases. There was a large discrepancy between clinically diagnosed depth of tumor invasion prior to surgery and depth of tumor invasion following surgery. Zinc finger E-box-binding homeobox 1 (ZEB1), an EMT-associated transcription factor, was expressed only in the sarcoma component in all 6 cases of ECS. The ECS cases had a significantly poorer prognosis compared with the 115 pT1 ESCC cases. The present study suggests that the depth of invasion of ECS lesions does not correspond with their respective size, and the EMT of the carcinoma component may affect the prognosis by overexpression of the ZEB1 gene.

12.
Langenbecks Arch Surg ; 404(1): 81-91, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30612151

RESUMO

BACKGROUND: Laparoscopy-assisted proximal gastrectomy (LAPG) with esophagogastrostomy using the double-flap technique has been reported to rarely cause gastroesophageal reflux. However, quantitative evaluation of the reflux has hardly been performed. The aim of this study was to clarify the superiority of the double-flap technique of LAPG with esophagogastrostomy compared with the OrVil technique in terms of preventing gastroesophageal reflux. METHODS: A total of 40 and 51 patients who underwent LAPG with esophagogastrostomy using the double-flap and OrVil techniques, respectively, for upper one-third gastric cancer were included in this study. Of these, 22 and 13 patients in the double-flap and OrVil groups, respectively, consented to undergo a 24-h impedance-pH monitoring test at 3 months postoperatively. Postoperative complications, including gastroesophageal reflux and anastomotic stricture, were assessed retrospectively. RESULTS: No significant differences were observed in the patients' background between both groups, except for a higher D1+ dissection rate observed in double-flap group than in the OrVil group (93% vs 25%, P < 0.001). Operative time was significantly longer in the double-flap group than in the OrVil group (353 min vs 280 min, P < 0.001). All reflux % time was significantly lower in the double-flap group than in the OrVil group (1.29% vs 2.62%, P = 0.043). On the other hand, the proportion of anastomotic stricture requiring endoscopic balloon dilatation was lower in the double-flap group than in the OrVil group but without statistical significance (18% vs 27%; P = 0.32). CONCLUSIONS: Despite its longer operative time and still relatively high anastomotic stricture rate, the double-flap technique would be better than the OrVil technique in terms of preventing gastroesophageal reflux in patients who underwent LAPG with esophagogastrostomy.


Assuntos
Gastrectomia/métodos , Refluxo Gastroesofágico/prevenção & controle , Laparoscopia/métodos , Complicações Pós-Operatórias/prevenção & controle , Neoplasias Gástricas/cirurgia , Retalhos Cirúrgicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Esofagostomia , Feminino , Gastrectomia/efeitos adversos , Refluxo Gastroesofágico/etiologia , Gastrostomia , Humanos , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
13.
Gastric Cancer ; 22(3): 598-606, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30284080

RESUMO

BACKGROUND: The prognosis of patients with gastric cancer with bulky node metastasis, linitis plastica (type 4), or large ulcero-invasive-type tumors (type 3) remains poor. We conducted a phase II study to evaluate the safety and efficacy of neoadjuvant chemotherapy with docetaxel, cisplatin, and S-1 (DCS) for establishing a new treatment modality that improves prognosis. METHODS: Patients received up to four 28-day cycles of DCS therapy (docetaxel at 40 mg/m2, cisplatin at 60 mg/m2 on day 1, and S-1 at 40 mg/m2 twice daily for 2 weeks) followed by gastrectomy with D2 nodal dissection. S-1 chemotherapy was administered for 1 year after surgical resection. The primary endpoint was the percentage of complete resections of the primary tumor with clear margins (R0 resection). The planned sample size was 40; this was calculated based on an expected R0 rate of 85% and a threshold R0 rate of 65%, with a one-sided alpha of 5% and a power of 90%. RESULTS: Between 2010 and 2017, 40 patients were enrolled. The R0 resection rate was 90%. The most common grade 3 or 4 adverse events during DCS therapy were leukocytopenia (27.5%), neutropenia (55.0%), and hyponatremia (22.5%). The most common grade 3 or 4 surgical morbidity was pancreatic fistula (12.5%); mortality was 0%. The pathological response rate was 57.5% with a grade 3 histological response rate of 8%. CONCLUSIONS: Neoadjuvant chemotherapy with DCS was feasible and showed a sufficient R0 resection rate. A future study with a sufficient follow-up period should confirm survival outcomes.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gastrectomia/métodos , Terapia Neoadjuvante , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Adulto , Idoso , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Docetaxel/administração & dosagem , Combinação de Medicamentos , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Ácido Oxônico/administração & dosagem , Cuidados Pós-Operatórios , Prognóstico , Estudos Prospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida , Tegafur/administração & dosagem , Adulto Jovem
14.
Cancer Sci ; 109(12): 3695-3706, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30264476

RESUMO

Promoter DNA methylation, which occurs on cytosine nucleotides across CpG islands, results in gene silencing and represents a major epigenetic alteration in human cancer. Methylation-specific PCR can amplify these modifications as markers in cancer cells. In the present work, we rigorously review the published literatures describing DNA methylation in the promoters of critical tumor suppressor genes; detection of promoter DNA methylation in various body fluids permits early detection of cancer cells during perioperative courses of clinical treatment. The latest whole-genome comprehensive explorations identified excellent epigenetic biomarkers that could be detected at high frequency with high specificity; these biomarkers, which are designated highly relevant methylation genes (HRMG), permit the discrimination of tumor tissues from the corresponding normal tissues; these markers are also associated with unique cancer phenotypes, including dismal prognosis. In humans, HRMG include the CDO1, GSHR, RASSF1 and SFRP1 genes, with these markers permitting discrimination depending on the organs tested. The combination of several HRMG increased the early detection of cancer and exhibited reliable surveillance potential in human body fluids. Cancer clinics using such epigenetic biomarkers are entering a new era of enhanced decision-making with the potential for improved cancer prognosis.


Assuntos
Biomarcadores Tumorais/genética , Metilação de DNA , Neoplasias/genética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Cisteína Dioxigenase/genética , Epigênese Genética/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Proteínas de Membrana/genética , Neoplasias/tratamento farmacológico , Regiões Promotoras Genéticas , Proteínas Supressoras de Tumor/genética
15.
Oncol Lett ; 16(3): 3281-3289, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30127926

RESUMO

The distribution of lymph node metastases, including recurrences, remains elusive in lower thoracic esophageal squamous cell carcinoma (LtESCC). The present study was a retrospective investigation into the optimized lymph node dissection range during LtESCC. Esophagectomies were performed on 163 patients with ESCC between 2009 and 2016, among whom 41 patients with LtESCC were examined. The rates of pathological and potential (including recurrences) metastases to lymph nodes and the prognosis (median, 34 months) were determined. Preoperative Docetaxel, Cisplatin and 5-fluorouracil chemotherapy was administered in >60% of cStage II/III LtESCC. During stage progression, abdominal lymph node metastasis rapidly becomes aggressive in LtESCC and lymph node metastases to the para-aortic area were more dominant than cervical and recurrent laryngeal nerve (RLN) areas. There were few control failures of regional lymph node metastases in LtESCC with surgery, if 1 unique case with cStage III who had metastases and recurrences of multiple lymph nodes during the clinical course was excluded. Defective lymph node dissection around the RLN did not worsen LtESCC prognosis with no RLN palsy. In the context of the potent preoperative chemotherapy and esophagectomy, lymph node dissection of cervical, para-aortic and RLN areas are putatively not mandatory to all LtESCC patients.

16.
Asian J Endosc Surg ; 11(4): 337-345, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29573227

RESUMO

INTRODUCTION: Despite technical improvements in laparoscopic gastrectomy, gastric stasis is still a serious problem in laparoscopy-assisted pylorus-preserving gastrectomy (LAPPG). The aim of this study was to investigate the factors that might cause gastric stasis in LAPPG. METHODS: From April 2004 through November 2012, 85 patients with cT1N0 middle-third gastric cancer who underwent LAPPG at Kitasato University Hospital; these patients were included in the present study. Infra-pyloric vein (IPV)-preserving LAPPG was performed in 41 patients. We compared the rate of gastric stasis in the IPV-preserving and the IPV-non-preserving groups, and analyzed the clinicopathological factors that might have caused gastric stasis. RESULTS: We did not demonstrate that preservation of the IPV could prevent gastric stasis in the early and late postoperative periods. Symptoms of gastric stasis were most frequently recognized 1 year after surgery. A significantly higher proportion of preoperative ASA class 2 patients had gastric stasis than did not (80.0% [12/15] vs 48.6% [34/70], P=0.02). Among the ASA class 2 patients, a significantly greater proportion of those with depressed activities of daily living than those with normal activities of daily living had gastric stasis (66.7% [4/6] vs 20.0% [8/40], P = 0.015). CONCLUSIONS: The clinical significance of the IPV preservation in LAPPG could not be demonstrated. LAPPG should be performed for ASA class 1 patients or those with maintained preoperative activities of daily living.


Assuntos
Adenocarcinoma/cirurgia , Gastrectomia/métodos , Gastroparesia/etiologia , Laparoscopia , Complicações Pós-Operatórias/etiologia , Piloro/cirurgia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Gastroparesia/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Período Pré-Operatório , Piloro/irrigação sanguínea , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Veias
17.
Oncol Lett ; 15(2): 1853-1860, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29434882

RESUMO

Curative gastrectomy and adjuvant chemotherapy using S-1 is a standard treatment for stage II/III gastric cancer in Japan. The purpose of the present study was to evaluate the prognostic relevance of fibroblast growth factor receptor (FGFR)2 expression in patients with stage II/III gastric cancer that underwent postoperative adjuvant chemotherapy with S-1. Formalin-fixed paraffin-embedded surgical specimens were retrospectively examined in 167 patients with stage II/III gastric cancer that underwent curative gastrectomy followed by adjuvant S1 chemotherapy. FGFR2 expression was measured using immunohistochemistry (IHC) staining. The IHC results for FGFR2 were as follows: Grade 1+, 32; grade 2+, 80; grade 3+, 55 patients. The FGFR2 expression level was not significantly associated with relapse-free or overall survival rates. However, in the diffuse type, the FGFR2 expression level tended to be negatively correlated with relapse-free survival. In particular, the proportion of patients who recurred >5 years following surgery was significantly larger in the FGFR2 grade 3+ group than in the grade 1+, 2+ group (4/22 vs. 1/35; P=0.047). The recurrent sites of long-term failure were mostly peritoneum among the diffuse type. To the best of our knowledge, the present study indicated for the first time that FGFR2 could predict long-term failure of adjuvant S-1 chemotherapy in curative advanced gastric cancer. There was no interaction between FGFR2 expression and patient survival outcomes in stage II/III gastric cancer. Patients with FGFR2 3+ in stage II/III gastric cancer should carefully be followed-up for >5 years after surgery.

18.
Oncol Lett ; 15(1): 1200-1210, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29399174

RESUMO

Globally, the incidence of esophago-gastric junction (EGJ) cancer is rapidly increasing. However, the proposed strategies for the treatment of these types of cancer are so diverse that there is no established consensus on the optimal treatment. The aim of the present study was to identify independent prognostic factors to delineate the optimal strategies for the treatment of EGJ cancer. The medical records of 150 patients with EGJ cancer who underwent curative surgery at the Kitasato University were retrospectively reviewed. The median follow-up period was 48 months. The patients with tumors that were classified as post-treatment primary tumor stage 3 [(y)pT3] or higher had a 5-year disease-specific survival (DSS) rate of 53%, whereas those with tumors that were classified as (y)pT0-2 had a 5-year DSS rate of 90%. Therefore, prognostic analysis was restricted to those tumors that were designated (y)pT3 or higher. A multivariate Cox's proportional hazards model identified the following independent prognostic factors that negatively influenced the DSS: i) Presence of tumors classified as post-treatment regional lymph node stage 1-3 [(y)pN1-3] [hazard ratio (HR), 3.62; 95% confidence interval (CI), 1.39-12.36]; ii) not undergoing treatment with splenectomy (HR, 2.40; 95% CI, 1.15-5.15); and iii) undergoing treatment with thoracotomy (HR, 2.07; 95% CI, 1.02-4.23). In patients with (y)pN0 tumors, the DSS rate was significantly improved for those who underwent splenectomy than for those who did not (P=0.024). In patients with (y)pN1-3 tumors, the DSS rate was significantly worse for those who underwent thoracotomy compared with those who did not (P=0.004). Splenectomy and thoracotomy may critically affect prognosis in locally advanced EGJ cancer that are classified as (y)pN0 and (y)pN1-3, respectively. Surgical treatments require optimization in order to improve prognoses in advanced EGJ cancer.

19.
Surg Today ; 48(5): 478-485, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29256147

RESUMO

PURPOSE: The prognosis of most patients with stage IB node-negative gastric cancer is good without postoperative chemotherapy; however, about 10% suffer recurrence and inevitably die. We conducted this study to establish the optimal indications for postoperative adjuvant chemotherapy in patients at risk of recurrence. METHODS: The subjects of this retrospective study were 124 patients with stage IB node-negative gastric cancer, who underwent gastrectomy at the Kitasato University East Hospital, between 2001 and 2010. We reviewed EGFR immunohistochemistry (IHC) as well as clinicopathological factors. RESULTS: Of the 124 patients, 47 (38%) showed intense EGFR IHC (2+ or 3+), with significantly less frequency than in stage II/III advanced gastric cancer (p < 0.001). According to univariate analysis, intense EGFR IHC was significantly associated with relapse-free survival (RFS) (p = 0.023) and associated with overall survival (OS) (p = 0.045) as well as vascular invasion (p = 0.031). On the multivariate Cox proportional hazards model, intense EGFR IHC(p = 0.016) was an independent prognostic predictor for RFS, and both vascular invasion (p = 0.033) and intense EGFR IHC (p = 0.031) were independent prognostic predictors for OS. The combination of both factors increased the risk of recurrence (p = 0.001). CONCLUSIONS: In stage IB node-negative gastric cancer, vascular invasion and intense EGFR IHC increase the likelihood of recurrence. We recommend adjuvant chemotherapy for such patients because of the high risk of metachronous recurrence.


Assuntos
Biomarcadores Tumorais/análise , Quimioterapia Adjuvante , Receptores ErbB/análise , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia , Idoso , Seguimentos , Gastrectomia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/irrigação sanguínea , Neoplasias Gástricas/patologia
20.
Asian J Endosc Surg ; 11(2): 160-164, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28856802

RESUMO

A 66-year-old man was referred to our hospital for treatment of esophagogastric junction cancer. He was diagnosed as cT2N0M0, and the esophageal invasion was found to be 1 cm from the esophagogastric junction. He underwent laparoscopy-assisted proximal gastrectomy and lower esophagectomy with esophagogastrostomy using the intrathoracic double-flap technique through the transhiatal approach. The operative time was 662 min (suturing time was 198 min), and blood loss was 200 mL. The operative time was much longer for this procedure than for esophagogastrostomy with the conventional (intra-abdominal) double-flap technique. The postoperative course was uneventful. No abnormal gastroesophageal reflux, esophageal motility, or lower esophageal sphincter (LES) pressure was demonstrated 3 months after the operation. Laparoscopic proximal gastrectomy and lower esophagectomy with esophagogastrostomy using the double-flap technique through the transhiatal approach is safe and feasible. It may be recommended for patients with esophagogastric junction cancer with esophageal invasion of about 1 cm.


Assuntos
Adenocarcinoma/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Junção Esofagogástrica/cirurgia , Gastrectomia/métodos , Laparoscopia/métodos , Neoplasias Gástricas/cirurgia , Idoso , Humanos , Masculino , Retalhos Cirúrgicos
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