Assuntos
Infecções por Mycobacterium não Tuberculosas , Infecções por Mycobacterium , Mycobacterium abscessus , Antibacterianos/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Testes de Sensibilidade Microbiana , Infecções por Mycobacterium/diagnóstico , Infecções por Mycobacterium/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológicoRESUMO
Colorectal cancer (CRC) can be classified into subtypes based on gene expression signatures. Patients with stage III enterocyte subtype of the CRC Assigner classifier have been shown to benefit from oxaliplatin adjuvant therapy. Here, we investigated whether single nucleotide polymorphisms (SNPs) in two enterocyte subtype-related genes, MS4A12 and CDX2, could predict the efficacy of oxaliplatin in first-line treatment for patients with metastatic CRC (mCRC). Three cohorts of patients were included: a discovery cohort receiving FOLFOX ± bevacizumab (BEV) (n = 146), a validation cohort receiving FOLFOXIRI + BEV (n = 230), and a control cohort receiving FOLFIRI + BEV (n = 228). SNPs were analyzed by PCR-based direct sequencing. In the discovery cohort, MS4A12 rs4939378 and CDX2 rs3812863 were identified as potential markers of efficacy. In the validation cohort, any G allele of MS4A12 rs4939378 was associated with longer progression-free survival (PFS) than the A/A variant in both univariate analysis (12.4 vs. 10.9 months, hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.49-0.99, P = 0.033) and multivariable analysis (HR 0.65, 95%CI 0.44-0.97, P = 0.035) in patients expressing wild-type KRAS, but not mutant KRAS. In contrast, longer PFS was observed for patients expressing the CDX2 rs3812863 G/G variant than any A allele in univariate analysis (32.3 vs. 10.3 months, HR 0.39, 95%CI 0.19-0.81, P = 0.004) only in patients expressing mutant KRAS. These findings were not observed in the control cohort. Thus, MS4A12 and CDX2 SNPs may have utility as predictive biomarkers of response to oxaliplatin-based treatment in mCRC patients.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/secundário , Enterócitos/metabolismo , Oxaliplatina/uso terapêutico , Polimorfismo Genético/genética , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Biomarcadores Tumorais , Fator de Transcrição CDX2/genética , Estudos de Coortes , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Compostos Organoplatínicos/uso terapêutico , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos Testes , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas p21(ras)/genéticaRESUMO
OBJECTIVES: The enterocyte subtype of colorectal cancer (CRC) responds favorably to oxaliplatin-based adjuvant treatment for stage III CRC. We examined the clinical significance of single-nucleotide polymorphisms (SNPs) in enterocyte-related genes MS4A12 and CDX2 in response to adjuvant treatment for stage III CRC. PATIENTS AND METHODS: A total of 350 patients with stage III CRC were included: 274 received adjuvant treatment with surgical resection (discovery cohort) and 76 received surgery alone (control cohort). In the discovery cohort, 68 patients received FOLFOX and 206 received oral fluoropyrimidine. SNPs were analyzed by PCR-based direct sequencing. RESULTS: In the discovery cohort, the MS4A12 rs4939378 G/G variant was associated with lower 5-year survival than any A allele [70% vs. 90%, univariate: hazard ratio (HR) 2.29, 95% confidence interval (CI) 1.03-5.06, P = 0.035; multivariate: HR 2.58, 95% CI 1.15-5.76, P = 0.021]. Patients with the CDX2 rs3812863 G/G variant had better overall survival than those with any A allele, although this was not significant in multivariate analysis (5 year-survival: 95% vs. 82%, univariate: HR 0.34, 95% CI 0.12-0.97, P = 0.034; multivariate: HR 0.39, 95% CI 0.13-1.11, P = 0.078). The SNPs did not show significant association with overall survival in the control cohort, and significant interaction was observed between MS4A12 genotypes and groups (P = 0.007). CONCLUSIONS: Our findings suggest that MS4A12 and CDX2 gene polymorphisms may predict outcome in stage III CRC. However, the clinical significance of SNPs for response to oxaliplatin may differ by tumor stage.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Fator de Transcrição CDX2/genética , Neoplasias Colorretais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Adulto , Idoso , Alelos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Terapia Combinada , Intervalo Livre de Doença , Enterócitos/efeitos dos fármacos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Polimorfismo de Nucleotídeo Único/genética , PrognósticoRESUMO
BACKGROUND/AIM: The Controlling Nutritional Status (CONUT) score is a useful nutritional evaluation, that is calculated from serum albumin, total cholesterol concentrations, and total lymphocyte count. This study aimed to investigate the association between the CONUT score and prognosis in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: The CONUT score was retrospectively calculated in 211 patients with mCRC receiving first-line chemotherapy. The patients were divided into three groups: the CONUT low-group (0-1), intermediate-group (2-4), and high-group (5-). The associations of the CONUT score with clinicopathological factors and survival outcomes were evaluated. RESULTS: The higher CONUT score was significantly associated with synchronous metastases, and no primary tumor resection. The higher CONUT score group showed a significant shorter progression-free survival (log-rank p<0.05) and overall survival (log-rank p<0.001). CONCLUSION: The CONUT score is a useful prognostic marker for predicting survival outcomes of patients with mCRC.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais , Avaliação Nutricional , Estado Nutricional/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Colesterol/sangue , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Albumina Sérica/análiseRESUMO
BACKGROUND/AIM: Sarcopenia is recognized as a condition related to quality of life and prognosis in patients with chronic liver disease, although no useful strategy for improving muscle volume and strength has been established. Here, we evaluated the efficacy of supplementation with branched-chain amino acid (BCAA) administration and walking exercise. PATIENTS AND METHODS: From December 2015 to July 2016, 33 Japanese outpatients with liver cirrhosis were enrolled (median: 67 years, HCV : HBV : alcohol : others=26 : 2 : 2 : 3, male : female=13 : 20, Child-Pugh A : B=30 : 3). None had a history of BCAA supplementation. After calculating the average number of daily steps using a pedometer for a 2-3-week period, BCAA supplementation (protein 13.5 g, 210 kcal/day) as a late evening snack and walking exercise (additional 2000 steps/day prescribed) were started. Body composition including muscle volume was analyzed using a bioelectrical impedance analysis method, and serological data and muscle strength (leg, handgrip) were evaluated at enrollment, and then 1, 2, and 3 months after starting the protocol. RESULTS: The median average number of daily steps was 3791 (interquartile range: 2238-5484). The average period of BCAA supplementation was 2.7±0.7 months. During the period from enrollment to 3 months after starting the protocol, HbA1c and NH3 were not significantly changed, whereas the BCAA/tyrosine ratio improved (4.3±1.35 to 5.24±2.04, P=0.001). In addition, the ratios for average daily steps (1.595, P=0.02) as well as muscle volume, leg strength, and handgrip strength (1.013, 1.110, and 1.056, respectively; all P<0.01) were increased at 3 months. CONCLUSION: BCAA supplementation and walking exercise were found to be effective and easily implemented for improving muscle volume and strength in liver cirrhosis patients.
Assuntos
Aminoácidos de Cadeia Ramificada/uso terapêutico , Suplementos Nutricionais , Cirrose Hepática/complicações , Músculo Esquelético/patologia , Sarcopenia/prevenção & controle , Caminhada/fisiologia , Idoso , Aminoácidos de Cadeia Ramificada/sangue , Amônia/sangue , Composição Corporal , Teste de Esforço , Terapia por Exercício , Feminino , Hemoglobinas Glicadas/metabolismo , Força da Mão , Humanos , Cirrose Hepática/sangue , Extremidade Inferior/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Sarcopenia/sangue , Sarcopenia/etiologia , Tirosina/sangueAssuntos
Antibacterianos/uso terapêutico , Hipertermia Induzida , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Mycobacterium marinum/isolamento & purificação , Idoso , Animais , Biópsia , Terapia Combinada/métodos , Antebraço , Mãos , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/microbiologia , Infecções por Mycobacterium não Tuberculosas/patologia , Infecções por Mycobacterium não Tuberculosas/terapia , Pele/microbiologia , Pele/patologia , Resultado do TratamentoRESUMO
PURPOSE: The most frequent bevacizumab-related side-effects are hypertension, proteinuria, bleeding and thromboembolism. To date, there is no biomarker that predicts anti-VEGF-associated toxicity. As autophagy inhibits angiogenesis, we hypothesised that single-nucleotide polymorphisms (SNPs) within autophagy-related genes may predict bevacizumab-mediated toxicity in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients with mCRC treated with first-line FOLFIRI and bevacizumab in two phase III randomised trials, namely the TRIBE trial (n = 219, discovery cohort) and the FIRE-3 trial (n = 234, validation cohort) were included in this study. Patients receiving treatment with FOLFIRI and cetuximab (FIRE-3, n = 204) served as a negative control. 12 SNPs in eight autophagy-related genes (ATG3/5/8/13, beclin 1, FIP200, unc-51-like kinase 1, UVRAG) were analysed by PCR-based direct sequencing. RESULTS: The FIP200 rs1129660 variant showed significant associations with hypertension in the TRIBE cohort. Patients harbouring any G allele of the FIP200 rs1129660 SNP showed a significantly lower rate of grade 2-3 hypertension compared with the A/A genotype (3% versus 15%, odds ratio [OR] 0.17; 95% confidence interval [CI], 0.02-0.73; P = 0.009). Similarly, G allele carriers of the FIP200 rs1129660 SNP were less likely to develop grade 2-3 hypertension than patients with an A/A genotype in the FIRE-3 validation cohort (9% versus 20%, OR 0.43; 95% CI, 0.14-1.11; P = 0.077), whereas this association could not be observed in the control cohort (12% versus 9%, OR 1.40; 95% CI, 0.45-4.04; P = 0.60). CONCLUSION: This is the first report demonstrating that polymorphisms in the autophagy-related FIP200 gene may predict hypertension in patients with mCRC treated with FOLFIRI and bevacizumab.
Assuntos
Autofagia/genética , Bevacizumab/efeitos adversos , Hipertensão/induzido quimicamente , Polimorfismo de Nucleotídeo Único/genética , Proteínas Tirosina Quinases/genética , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteínas Relacionadas à Autofagia , Bevacizumab/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Cetuximab/administração & dosagem , Quimioterapia Adjuvante , Neoplasias Colorretais/tratamento farmacológico , Feminino , Fluoruracila/administração & dosagem , Genótipo , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metástase NeoplásicaRESUMO
For decades, hyperbaric oxygen therapy has been considered a treatment option in patients with chronic radiation-induced proctitis after pelvic radiation therapy. Refractory cases of chronic radiation-induced proctitis include ulceration, stenosis, and intestinal fistulas with perforation. Appropriate treatment needs to be given. In the present study, we assessed the efficacy of hyperbaric oxygen therapy in five patients with radiation-induced rectal ulcers. Significant improvement and complete ulcer resolution were observed in all treated patients; no side-effects were reported. Hyperbaric oxygen therapy has a low toxicity profile and appears to be highly effective in patients with radiation-induced rectal ulcers. However, hyperbaric oxygen therapy alone failed to improve telangiectasia and easy bleeding in four of the five patients; these patients were further treated with argon plasma coagulation (APC). Although hyperbaric oxygen therapy may be effective in healing patients with ulcers, it seems inadequate in cases with easy bleeding. Altogether, these data suggest that combination therapy with hyperbaric oxygen therapy and APC may be an effective and safe treatment strategy in patients with radiation-induced rectal ulcers.
Assuntos
Braquiterapia/efeitos adversos , Oxigenoterapia Hiperbárica/métodos , Proctite/terapia , Lesões por Radiação/patologia , Lesões por Radiação/terapia , Doenças Retais/terapia , Adulto , Idoso , Braquiterapia/métodos , Relação Dose-Resposta à Radiação , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Proctite/etiologia , Lesões por Radiação/diagnóstico , Dosagem Radioterapêutica , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodos , Doenças Retais/etiologia , Doenças Retais/patologia , Estudos de Amostragem , Resultado do Tratamento , Úlcera/etiologia , Úlcera/patologia , Úlcera/terapia , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/cirurgiaRESUMO
BACKGROUND: Positron emission tomography (PET) response criteria in solid tumors were recently proposed as a standardized method for the metabolic and quantitative assessment of response to chemotherapy. However, use of these criteria is limited in many institutions because of the need for exclusive software. This study was designed to clarify whether tumor to normal esophageal (T/N) ratio on (18)F-fluorodeoxyglucose PET/computed tomography could predict response to neoadjuvant chemotherapy and stratify prognosis in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Clinicopathological data were collected for 73 patients with ESCC who received neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil followed by curative resection. The right liver lobe and normal esophagus were utilized as reference tissues for diagnosing complete metabolic response (CMR). Statistical methods included Kaplan-Meier analysis and univariate and multivariate Cox proportional hazards regression analyses. RESULTS: CMR was achieved in 24 patients on the basis of maximum standardized uptake value (SUVmax) and in 11 on the basis of SUVmax evaluation with T/N ratio. Although prognosis was poorer in patients who achieved CMR than partial metabolic response based on SUVmax, the responses were significantly correlated with disease-free survival (DFS) based on SUVmax evaluation with T/N ratio (P = 0.0011). Receiver operating characteristic curve analysis showed that SUVmax evaluation with T/N ratio was the best predictor of pGrade 3. Multivariate analysis showed that SUVmax evaluation with T/N ratio was an independent predictor of DFS in patients with pGrade 1 pathologic response. CONCLUSIONS: SUVmax evaluation with T/N ratio is useful for evaluating the effects of neoadjuvant chemotherapy in patients with ESCC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/tratamento farmacológico , Esôfago/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Docetaxel , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Esofagectomia , Feminino , Fluordesoxiglucose F18 , Fluoruracila/administração & dosagem , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Taxoides/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND/AIM: Preoperative chemoradiotherapy followed by total mesorectal excision (TME) is the standard treatment for stage III lower rectal cancer worldwide. However, in Japan, the standard treatment is TME with lateral pelvic lymph node dissection (LPLD) followed by adjuvant chemotherapy. We examined the safety and efficacy of adjuvant therapy with oxaliplatin, leucovorin, and 5-fluorouracil (modified FOLFOX6) after TME with LPLD. PATIENTS AND METHODS: This retrospective study included 33 patients who received modified FOLFOX6 after TME with LPLD for stage III lower rectal cancer. RESULTS: The overall completion rate of 12 cycles of adjuvant modified FOLFOX6 was 76%. Grade 3 or 4 neutropenia was observed in eight patients (24%). Sensory neuropathy was observed in 32 patients (97%) with 4 (12%) having a grade 3 event. The disease-free survival (DFS) rate was 45% at 3 years. CONCLUSION: Adjuvant modified FOLFOX6 was feasible in patients with stage III lower rectal cancer after TME with LPLD.
Assuntos
Excisão de Linfonodo , Neoplasias Retais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Neoplasias Retais/mortalidade , Neoplasias Retais/cirurgia , Estudos RetrospectivosRESUMO
INTRODUCTION: S-1 is an oral fluoropyrimidine that consists of tegafur, 5-chloro-2, 4-dihydroxypyridine and potassium oxonate. It has been developed as a prodrug of 5-fluorouracil with the goal of improving therapeutic efficacy and tolerability. AREAS COVERED: This review aims to provide an evidence-based update of clinical trials that have investigated the clinical efficacy, adverse-event profile, dosage and administration of S-1, given alone or in combination with conventional chemotherapeutics and new target-oriented drugs, in the management of colorectal cancer (CRC). Additionally, differences in the tolerability and pharmacokinetics of S-1 between Caucasians and Asians have been described. Finally, the therapeutic efficacy of S-1 regarding metastatic CRC or postoperative CRC has been discussed. Available data have stimulated further research, including Phase III trials for the treatment of advanced CRC. EXPERT OPINION: Treatment using S-1 combined with oxaliplatin (± bevacizumab) and irinotecan has achieved promising results in terms of feasibility, safety and effectiveness. Furthermore, S-1 is an acceptable treatment as adjuvant chemotherapy for colon cancer.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Compostos Organoplatínicos/uso terapêutico , Ácido Oxônico/uso terapêutico , Tegafur/uso terapêutico , Animais , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/uso terapêutico , Quimioterapia Adjuvante , Colo/efeitos dos fármacos , Colo/patologia , Neoplasias Colorretais/patologia , Combinação de Medicamentos , Humanos , Irinotecano , Metástase Neoplásica/tratamento farmacológico , Metástase Neoplásica/patologia , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Reto/efeitos dos fármacos , Reto/patologia , Tegafur/administração & dosagem , Tegafur/efeitos adversosRESUMO
BACKGROUND: The role of adjuvant chemotherapy for stage IV colorectal cancer has so far been under-investigated. The aim of this study was to assess the feasibility and short-term outcome of adjuvant chemotherapy with the FOLFOX regimen following liver resection for patients with colorectal liver metastasis (CRLM). METHODS: From May 2005 to September 2010, 86 patients with CRLM underwent hepatic resection in the Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University. Of these patients, 24 received FOLFOX4 or modified FOLFOX6 as postoperative adjuvant chemotherapy. RESULTS: Nineteen male and 5 female patients received adjuvant chemotherapy following liver resection. Twenty-one (87.5 %) of these patients completed 6 cycles of adjuvant chemotherapy. Five patients required a dose reduction due to neutropenia, and the dose intensities of oxaliplatin and 5-FU were 93.6 and 94.1 %, respectively. There were no severe adverse events from the treatments. The median follow-up period was 48.4 months. Recurrences developed in 12 patients, and 3 patients died during the follow-up period. The 3- and 5-year disease-free survival and overall survival were 51.6 and 45.1 % and 95.5 and 76.0 %, respectively. CONCLUSIONS: Adjuvant FOLFOX is feasible and might provide a good prognosis for CRLM patients who undergo liver resection.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Estudos de Viabilidade , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Hepatectomia , Humanos , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Estudos Prospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Genome-wide DNA hypomethylation plays a role in genomic instability and carcinogenesis. DNA methylation in the long interspersed nucleotide element 1 L1 (LINE-1) repetitive element is a good indicator of global DNA methylation level. LINE-1 methylation is a useful marker for predicting cancer prognosis and monitoring efficacy of adjuvant therapy. Nonetheless, no study has examined LINE-1 methylation in esophageal squamous cell carcinoma (ESCC). The aim of this study is to assess the precision of sodium bisulfite conversion and polymerase chain reaction (PCR) pyrosequencing assay for evaluating LINE-1 methylation in ESCC. METHODS: To measure assay precision, we performed bisulfite conversion on 5 different DNA specimen aliquots (bisulfite-to-bisulfite) and repeated PCR pyrosequencing five times (run to run). Second, to assess heterogeneity of LINE-1 methylation levels within tumor, we made 5 different tissue sections from one tumor and examined LINE-1 methylation level of each section (section to section). Third, to evaluate LINE-1 methylation status in ESCC, we applied this assay to 30 ESCCs and 30 matched normal esophageal mucosa. RESULTS: Bisulfite-to-bisulfite standard deviation (SD) ranged from 1.44 to 2.90 (median 2.32) in ESCCs; and 0.57 to 4.02 (median 1.23) in normal esophagus. Run-to-run SD ranged from 0.63 to 3.25 (median 1.54) in ESCCs. Section-to-section SD ranged from 1.37 to 3.31 (median 1.94). ESCC tissues showed significantly lower levels of LINE-1 methylation than matched normal mucosa (P < .0001; n = 30). There was no significant relationship between LINE-1 methylation level and tumor stage (P = 0.14). CONCLUSIONS: Bisulfite conversion and PCR pyrosequencing assay can measure LINE-1 methylation in ESCC, and may be useful in clinical and research settings.