RESUMEN
BACKGROUND: Various functions in elderly patients with esophageal cancer deteriorate easily and their quality of life can be adversely affected by treatment. The age groups covered in previous studies are wide, and the impact on the elderly individuals is unknown. This study examined changes in quality of life scores after preoperative chemotherapy to clarify aspects of physical, psychological, and social quality of life in elderly patients with esophageal cancer. METHODS: Thirty-six patients aged over 65 years, who were scheduled to undergo preoperative chemotherapy for esophageal cancer surgery, were enrolled. The survey questionnaire comprised the EORTC QLQ-C30 Japanese Language Version, EORTC QLQ-OES 18 Japanese Language Version, and G8. The surveys were conducted before chemotherapy (pre-CT) and after chemotherapy (post-CT). RESULTS: In the functional scale of QLQ-C 30, physical functioning decreased significantly, while emotional functioning increased significantly post-CT (p = 0.021, p = 0.030, respectively). Global health status was not changed. In QLQ-OES18, the mean symptom scale score decreased significantly for dysphagia, trouble swallowing saliva, choking, eating, reflux, and pain post-CT (p = 0.014, p = 0.034, p = 0.033, p = 0.022, p = 0.026, p = 0.016, respectively). The mean G8 score decreased significantly from 11.7 to 10.7 (p = 0.022) post-CT, but the proportion of patients with dysfunction decreased. CONCLUSIONS: Quality of life scores of elderly patients with esophageal cancer who received preoperative chemotherapy decreased in terms of physical function but improved in terms of esophageal cancer symptoms and mental function. Our results suggest that alleviation of symptoms contributed to the improvements in mental health.
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Neoplasias Esofágicas , Calidad de Vida , Anciano , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/psicología , Neoplasias Esofágicas/cirugía , Humanos , Encuestas y CuestionariosRESUMEN
The use of azacitidine (AZA) has been known to lead to a high incidence of hematotoxic adverse events. The aims of this study were to identify the risk factors for thrombocytopenia after the administration of AZA and to analyze time to the initial platelet transfusion. Sixty-two patients with myelodysplastic syndrome (MDS), who were treated with AZA in Gifu Municipal Hospital between March 2012 and June 2020, were included in this study. The risk factors for thrombocytopenia were identified using univariate analysis of patient characteristics, disease type, and laboratory values immediately before the start of treatment. Variables with p<0.2 identified in the univariate analysis were used as independent variables in the multivariate analysis. This analysis identified "creatinine clearance (CCr) <60 mL/min" as a significant factor (odds ratio, 4.790; 95% confidence interval [CI], 1.380-16.70; p=0.014). Subsequently, time in days to the initial platelet transfusion after the initial administration of AZA was analyzed using the log-rank test. The overall median time in days to platelet transfusion was 370 days. The log-rank test was used to determine the influence of patient characteristics, disease type, and laboratory values immediately before the start of treatment. The subsequent Cox proportional hazard regression analysis using variables with p<0.2 as independent variables identified "hemoglobin (Hb) <8.0 g/dL" as a significant factor (hazard ratio, 2.143; 95% CI, 1.001-4.573; p=0.048). The results of this study led to the following clinical implications: first, patients with CCr of <60 mL/min at the start of treatment should be treated with caution due to the risk of thrombocytopenia. Second, patients with Hb of <8.0 g/dL at the start of treatment may require platelet transfusion in the early stage of treatment.
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Síndromes Mielodisplásicos , Trombocitopenia , Azacitidina/efectos adversos , Humanos , Síndromes Mielodisplásicos/inducido químicamente , Síndromes Mielodisplásicos/tratamiento farmacológico , Transfusión de Plaquetas/efectos adversos , Factores de Riesgo , Trombocitopenia/inducido químicamente , Trombocitopenia/tratamiento farmacológico , Trombocitopenia/epidemiologíaRESUMEN
BACKGROUND: Extramammary Paget's disease (EMPD) is a rare malignant skin cancer. One of the hallmarks of cancers, including EMPD, is an enhancement of aerobic glycolysis, which is also known as the Warburg effect. In the last step of glycolysis, the enzyme lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactic acid, the accumulation of which contributes to the creation of an acidic tumour microenvironment. This in turn results in immunosuppression in various types of cancers. However, the contribution of these pathways has not been well-studied in EMPD. OBJECTIVE: To investigate the significance of the Warburg effect and its contribution to the tumour immune microenvironment in EMPD. METHODS: The mRNA expression levels of molecules involved in glycolysis and immune-related cytokines were examined by ddPCR. The number of immune cells was assessed by immunohistochemistry (IHC). RESULTS: The levels of two glycolytic enzymes, HK2 and LDHA, in tumour tissues were significantly increased compared to those in paired-normal tissues. IHC analyses revealed increased numbers of PD-L1+ , PD-1+ , CD163+ M2 macrophages, Iba1+ macrophages and Foxp3+ Tregs that were associated with high LDHA levels in EMPD. ddPCR demonstrated that multiple cytokines including IL-4, IL-6, IL-10, TGF-ß and CCL-2 were upregulated and associated with high LDHA levels in EMPD. Statistical analyses showed that IL-6 mRNA expression correlated with the number of CD163+ , Iba-1+ and Foxp3+ cells. CONCLUSION: The Warburg effect contributes to immunomodulation in the tumour microenvironment and further elucidation may lead to better understanding of the pathogenesis of EMPD.
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L-Lactato Deshidrogenasa/genética , Enfermedad de Paget Extramamaria/inmunología , Microambiente Tumoral , Humanos , Inmunohistoquímica , Enfermedad de Paget Extramamaria/genéticaRESUMEN
BACKGROUND: Although carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA) are useful markers for extramammary Paget disease (EMPD), serum CEA and CYFRA levels are not elevated in most patients with EMPD without metastasis. Cell-free (cf)DNA has attracted attention as an indicator of clinical conditions in several cancers. OBJECTIVES: To identify further useful biomarkers for the detection of EMPD, including early lesions, and to study the clinical implications of cfDNA in EMPD. METHODS: cfDNA were isolated from serum of patients with EMPD with and without metastasis, and from healthy volunteers. Serum extracts were amplified using polymerase chain reaction. RESULTS: Serum cfDNA levels were significantly elevated in patients with EMPD with or without metastasis compared with those in healthy controls. Serum cfDNA was a better diagnostic marker for the presence of EMPD than serum CYFRA. Moreover, the postoperative serum cfDNA levels were significantly lower than those from the preoperative samples, and the change in serum cfDNA levels reflected the clinical courses of patients with EMPD treated with chemotherapy. CONCLUSIONS: Taking the evidence together, serum cfDNA levels may be a useful marker for diagnosis and disease progression in EMPD. What's already known about this topic? Serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA) are not elevated in most patients with extramammary Paget disease (EMPD) without metastasis. Cell-free (cf)DNA has attracted attention as an indicator of clinical conditions in several cancers. There are few reports of the clinical implications of cfDNA in dermatology. What does this study add? Serum cfDNA levels were significantly elevated in patients with EMPD with or without metastasis compared with those in healthy controls. Postoperative serum cfDNA levels were significantly lower than those from the preoperative samples. Changes in serum cfDNA levels reflected the clinical courses of patients with EMPD treated with chemotherapy. What is the translational message? Serum cfDNA levels in patients with EMPD are a useful marker for the detection of EMPD, including localized EMPD. Changes in serum cfDNA levels in an individual patient may reflect the clinical course of EMPD.
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Biomarcadores de Tumor/sangre , Ácidos Nucleicos Libres de Células/sangre , Enfermedad de Paget Extramamaria/diagnóstico , Neoplasias Cutáneas/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias/sangre , Biomarcadores de Tumor/genética , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Humanos , Queratina-19/sangre , Masculino , Persona de Mediana Edad , Enfermedad de Paget Extramamaria/sangre , Enfermedad de Paget Extramamaria/genética , Enfermedad de Paget Extramamaria/cirugía , Periodo Posoperatorio , Periodo Preoperatorio , Piel/patología , Neoplasias Cutáneas/sangre , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/cirugía , Adulto JovenRESUMEN
Trichohyalin-like (TCHHL)1 is a member of the fused-type S100 protein family. Its function remains unknown, although it has been reported to be expressed in the basal layer of the normal epidermis. The aim of this study was to investigate the effects of ultraviolet B (UVB) irradiation on the expression of TCHHL1 in human skin xenotransplants. Expression of TCHHL1 mRNA was increased in the UVB-exposed skin 2 days after UVB irradiation. TCHHL1 was immunohistochemically detected in the basal layers after sham irradiation. However, on Day 2 after irradiation, the TCHHL1 signals were spread throughout the basal and spinous layers of the irradiated skin, with increased expression of cytokeratin 14 and a dramatic increase in the number of Ki67-positive cells observed. These results show that TCHHL1 is a novel protein whose expression can be increased by UVB irradiation. In addition, this study experimentally shows that TCHHL1 is expressed in proliferative keratinocytes.
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Expresión Génica/efectos de la radiación , Proteínas S100/genética , Proteínas S100/metabolismo , Piel/metabolismo , Piel/efectos de la radiación , Rayos Ultravioleta , Animales , Humanos , Queratina-14/metabolismo , Queratinocitos/metabolismo , Queratinocitos/efectos de la radiación , Antígeno Ki-67/metabolismo , Ratones , ARN Mensajero/metabolismo , Trasplante de Piel , Trasplante HeterólogoRESUMEN
Chemotherapy for cancer is increasingly implemented in the outpatient setting. Pharmacists contribute to cancer treatment by conducting counseling during outpatient chemotherapy visits. They provide guidance on drug treatment, side effects, and side effect countermeasures on every visit. However, there have been few economic evaluations of pharmacist involvement in outpatient chemotherapy. Therefore, we performed a cost utility analysis. We assigned usual care (control) and pharmacist counseling to two groups of 19 patients receiving outpatient chemotherapy for breast cancer at Gifu Municipal hospital. Quality of life was measured at three timepoints before and during chemotherapy treatment using the EuroQol 5 dimension instrument (EQ-5D). EQ-5D values across the timepoints were 0.831, 0.757, and 0.791 for the control group, and 0.882, 0.883, and 0.921 for the pharmacist counseling group. The additional cost in the pharmacist counseling group was 2,227 yen per counseling session. The change in quality-adjusted life years (QALY) was a maximum of -0.021±0.186 in the control group and 0.007±0.199 in the pharmacist counseling group. The maximum cost for one QALY was 1,360,558 yen (≈12,460 US dollars). Pharmacists' counseling in outpatient cancer chemotherapy for breast cancer patients had an acceptable incremental cost-effect ratio, contributing to improved patient quality of life without significant additional expenditure to healthcare.
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Antineoplásicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Farmacéuticos/organización & administración , Servicio de Farmacia en Hospital/organización & administración , Adulto , Anciano , Análisis Costo-Beneficio , Consejo/economía , Consejo/métodos , Femenino , Humanos , Japón , Persona de Mediana Edad , Pacientes Ambulatorios , Farmacéuticos/economía , Servicio de Farmacia en Hospital/economía , Rol Profesional , Calidad de Vida , Años de Vida Ajustados por Calidad de VidaRESUMEN
Although no consensus is available on the treatment of esophageal squamous cell carcinoma (ESCC) invading adjacent organs (T4), establishing effective induction treatments is crucial to altering an unresectable status and achieving curative resection. Here, we evaluated the efficacy of chemotherapy using 5-fluorouracil, cisplatin, and docetaxel (DCF) as the initial induction treatment for T4 ESCC. Fifty patients without distant metastasis who underwent initial induction chemotherapy using DCF for T4 ESCC were propensity score-matched with 50 patients who underwent radiotherapy concurrent with cisplatin and 5-fluorouracil (CRT). In the DCF group, 24 (48.0%) patients underwent surgery, achieving a 64% clinical response rate compared to 72.0% for induction CRT. CRT was also performed in another 24 (48.0%) patients in the DCF group in whom surgical resection was not indicated. The DCF group had significantly higher overall resectability than the CRT group (78.0% vs. 48.0%, P = 0.0017). The esophageal perforation rate during induction treatments was significantly lower in the DCF group than the CRT group (4.0% vs. 18.0%, P = 0.0205). Prognosis was significantly better in the DCF group than the CRT group (5-year cancer-specific survival 42.1% vs. 22.2%, P = 0.0146). Thus, induction DCF chemotherapy in patients with T4 ESCC reduced esophageal perforation and increased overall resectability, leading to better survival than CRT alone. Therefore, DCF chemotherapy may be an effective and safe option for initial induction treatment of T4 ESCC.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Células Escamosas/terapia , Cisplatino/administración & dosificación , Neoplasias Esofágicas/terapia , Fluorouracilo/administración & dosificación , Quimioterapia de Inducción/métodos , Taxoides/administración & dosificación , Anciano , Carcinoma de Células Escamosas/patología , Quimioradioterapia/métodos , Docetaxel , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago , Esofagoscopía/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Resultado del TratamientoRESUMEN
Reflux following an esophagectomy with gastric conduit reconstruction in the posterior mediastinum is a clinically significant problem. In this study, we investigated the frequency and impact of reflux on the quality of life (QOL) among 158 patients who underwent an esophagectomy for esophageal cancer using an original questionnaire and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Version 3.0 (EORTC QLQ-C30). Reflux frequency was assessed using the original questionnaire. The number of patients who complained of reflux every day, two or three times a week, once a week, or less than once a week was 16 (10.1%), 21 (13.3%), 26 (16.5%), and 60 (38.0%), respectively. Out of 35 patients (22.2%) reported no reflux symptoms. Patients were divided into two groups: those with reflux ≥ once/week (63 patients) and those with low frequency of symptoms (95 patients). Time elapsed following surgery was the only factor to influence reflux frequency. Reflux frequency decreased within two years of surgery; however, the frequency plateaued after more than two years. QOL was assessed using the EORTC QLQ-C30. The ≥ once/week reflux group had a significantly lower global health status score than the low-frequency reflux group (59.6 ± 24.2 vs. 70.8 ± 20.7; P = 0.007). In addition, the ≥ once/week reflux group had a significantly lower social functioning score than the low-frequency reflux group (81.6 ± 24.1 vs. 88.4 ± 19.8; P = 0.035). Regarding symptoms, the ≥ once/week reflux group had significantly higher scores for fatigue, nausea, and vomiting, dyspnea and insomnia compared to the low-frequency reflux group (fatigue: 42.4 ± 21.9 vs. 28.9 ± 18.4, P < 0.001; nausea and vomiting: 17.3 ± 17.1 vs. 4.9 ± 10.6, P < 0. 001; dyspnea: 29.2 ± 26.0 vs. 21.7 ± 26.8, P = 0.043; insomnia: 22.2 ± 31.1 vs. 10.5 ± 21.7, P = 0.015). Thus, reflux after an esophagectomy was associated with a lower QOL.
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Esofagectomía/efectos adversos , Reflujo Gastroesofágico/psicología , Procedimientos de Cirugía Plástica/efectos adversos , Complicaciones Posoperatorias/psicología , Calidad de Vida/psicología , Anciano , Neoplasias Esofágicas/cirugía , Esofagectomía/métodos , Unión Esofagogástrica/cirugía , Femenino , Reflujo Gastroesofágico/epidemiología , Reflujo Gastroesofágico/etiología , Humanos , Masculino , Mediastino/cirugía , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Periodo Posoperatorio , Procedimientos de Cirugía Plástica/métodos , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
BACKGROUND: This phase II trial evaluated the efficacy of cisplatin and fluorouracil (CF)-based combination neoadjuvant chemotherapy on the outcome of patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC). We compared the recurrence-free survival (RFS) associated with CF plus Adriamycin (ACF) with that associated with CF plus docetaxel (DCF) to select an alternative regimen in a new phase III trial investigating the optimal neoadjuvant treatment of patients with ESCC. PATIENTS AND METHODS: Patients with resectable advanced ESCC were randomly assigned to either ACF (Adriamycin 35 mg/m2, cisplatin 70 mg/m2 i.v. on day 1, fluorouracil 700 mg/m2 continuous infusion for 7 days) every 4 weeks or DCF (docetaxel 70 mg/m2, cisplatin 70 mg/m2 i.v. on day 1, fluorouracil 700 mg/m2 continuous infusion for 5 days) every 3 weeks. Surgery was scheduled after completion of two cycles of chemotherapy. The primary end point was RFS, analyzed by the intention-to-treat. RESULTS: Between October 2011 and October 2013, 162 patients at 10 institutions were enrolled in the study, all of whom were eligible and randomly assigned to the two groups (81 to the ACF group and 81 to the DCF group). The R0 resection rates for the ACF and DCF groups were equivalent (95.9% versus 96.2%, P = 0.93). The 2-year RFS and overall survival rates for DCF versus ACF were 64.1% versus 42.9% (hazard ratio 0.53, 95% confidence interval 0.33-0.83, P = 0.0057) and 78.6% versus 65.4% (P = 0.08), respectively. CONCLUSION: Compared with ACF, DCF chemotherapy was associated with prolonged RFS for patients with resectable advanced ESCC. Thus, DCF chemotherapy has potential as a standard neoadjuvant therapy for resectable ESCC. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry of Japan (identification number UMIN000004555/000004616).
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Doxorrubicina/administración & dosificación , Neoplasias Esofágicas/tratamiento farmacológico , Taxoides/administración & dosificación , Adulto , Anciano , Carcinoma de Células Escamosas/mortalidad , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Supervivencia sin Enfermedad , Docetaxel , Doxorrubicina/efectos adversos , Neoplasias Esofágicas/mortalidad , Carcinoma de Células Escamosas de Esófago , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Taxoides/efectos adversos , Resultado del TratamientoRESUMEN
Although 3-field lymph node dissection (3-FLD) is often performed for thoracic esophageal squamous cell carcinoma (ESCC), the clinical effects of cervical lymph node dissection in addition to mediastinal and abdominal dissections on postoperative complications remain unclear. A total of 367 ESCC patients who underwent curative esophagectomy for thoracic esophageal cancer in our hospital from 2010 to 2015 were included in the study: 157 patients who underwent 2-field lymph node dissection (2-FLD) and 210 patients who underwent 3-FLD. Clinicopathological parameters and postoperative complications based on the Clavien-Dindo classification were compared between the two groups. We performed propensity score matching (PSM) analyses to compare the groups with well-balanced backgrounds. In terms of patient background, clinical T (p < 0.001), N (p < 0.001), and M (p = 0.002) stage of tumor was significantly more advanced; therefore, preoperative treatment was more frequently performed in the 3-FLD group than in the 2-FLD group (91.0% vs. 79.0%, P< 0.001). However, perioperative parameters including operation time, blood loss, and the number of dissected mediastinal and abdominal lymph nodes did not differ between the groups. In terms of postoperative complications, the occurrence rate of pneumonia increased significantly in patients with 3-FLD compared to 2-FLD (grade III or higher: 10.5% vs. 3.2%, P= 0.025). Although the duration of systemic inflammatory response syndrome (SIRS) was longer in the 3-FLD group than in the 2-FLD group (median 3 days vs. 2 days, P= 0.025), other postoperative parameters (including the highest level of postoperative serum C-reactive protein, intensive care unit stay, re-operation rate, and postoperative hospital stay) were similar between the groups. After PSM, the differences in the background between the groups disappeared. PSM analysis showed that there was no significant difference in each complication between the groups. The duration of SIRS tended to be longer in the 3-FLD group than in the 2-FLD group, but the difference was not significant. The field of lymphadenectomy negatively impacted the short-term outcome in ESCC patients in terms of pneumonia and inflammatory response. However, because the results of the PSM analyses indicate that the short-term outcome was similar between the two groups, 3-FLD could be as feasible as 2-FLD in ESCC patients.
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Carcinoma de Células Escamosas/cirugía , Neoplasias Esofágicas/cirugía , Esofagectomía/métodos , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/cirugía , Complicaciones Posoperatorias/etiología , Abdomen , Adulto , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/análisis , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/patología , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago , Femenino , Humanos , Tiempo de Internación , Ganglios Linfáticos/patología , Masculino , Mediastino , Persona de Mediana Edad , Cuello , Tempo Operativo , Neumonía/etiología , Periodo Posoperatorio , Puntaje de Propensión , Estudios Prospectivos , Estudios Retrospectivos , Síndrome de Respuesta Inflamatoria Sistémica/etiología , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: [(18) F]fluorodeoxyglucose (FDG)-PET has been used to evaluate the response of primary tumours to neoadjuvant therapy for oesophageal cancer. The clinical significance of the number of PET-positive nodes before and after therapy has not been investigated previously. METHODS: [(18) F]FDG-PET was performed before and 2-3 weeks after completion of neoadjuvant chemotherapy to identify the number of PET-positive nodes, and these numbers were assessed in relation to metabolic changes in the primary tumour. RESULTS: Of 302 patients in total, 90 had no PET-positive nodes, 83 had one, 59 had two and 70 patients had three or more positive nodes before therapy. After treatment, the numbers were: none in 207 patients, one in 59, two in 20 and three or more in 16 patients. The number of PET-positive nodes after treatment was influenced by both the number of PET-positive nodes before therapy and the response to preoperative therapy, and correlated with the number of metastatic lymph nodes. Overall survival was longer in patients who had no PET-positive nodes after treatment than in those who had one or more. Multivariable analysis identified the numbers of PET-positive nodes before and after chemotherapy as independent prognostic factors, together with clinical response, tumour depth and lymph node involvement. CONCLUSION: The number of PET-positive nodes after treatment correlated with survival in patients with oesophageal cancer who underwent neoadjuvant chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias Esofágicas/tratamiento farmacológico , Esofagectomía , Ganglios Linfáticos/diagnóstico por imagen , Tomografía de Emisión de Positrones , Adulto , Anciano , Antineoplásicos/administración & dosificación , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/cirugía , Quimioterapia Adyuvante , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/cirugía , Femenino , Fluorodesoxiglucosa F18 , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Análisis Multivariante , Radiofármacos , Resultado del TratamientoRESUMEN
Erythropoietic protoporphyria (EPP) is an inherited cutaneous porphyria caused by both the partial deficiency of ferrochelatase (FECH) and the existence of cytosine at IVS3-48 in trans to a mutated FECH allele. However, physicians occasionally encounter patients with EPP with a mild phenotype associated with a slight increase in the erythrocyte-free protoporphyrin concentration and no FECH gene mutations. In this study, genetic analyses were performed on three patients with a mild phenotype of EPP, with photosensitivity, slightly increased erythrocyte-free protoporphyrin concentrations and only a few fluorocytes in the peripheral blood. After obtaining the patients' and their parents' informed consent, a direct sequence analysis of the FECH gene and a restriction fragment length polymorphism analysis were performed on samples from the patients. The FECH gene mutation was not detected in the direct sequence analyses in any of the patients. However, all three patients had the homozygous IVS3-48C polymorphism. These findings suggest that homozygous IVS3-48C polymorphism of the FECH gene is associated with a slight elevation of the protoporphyrin level in erythrocytes, resulting in a mild EPP phenotype.
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Ferroquelatasa/genética , Mutación/genética , Polimorfismo Genético/genética , Protoporfiria Eritropoyética/genética , Niño , ADN Recombinante/genética , Femenino , Homocigoto , Humanos , Masculino , RecurrenciaAsunto(s)
Hipopigmentación/genética , Hipopigmentación/patología , Mosaicismo , Femenino , Humanos , Lactante , Pigmentación de la Piel , Luz SolarAsunto(s)
Enfermedades del Pie , Terapia por Láser , Láseres de Gas , Verrugas , Humanos , Láseres de Gas/uso terapéuticoAsunto(s)
Dermatofibrosarcoma/genética , Proteínas de Fusión Oncogénica/genética , Neoplasias Cutáneas/genética , Adulto , Anciano , Puntos de Rotura del Cromosoma , Colágeno Tipo I/genética , Cadena alfa 1 del Colágeno Tipo I , Dermatofibrosarcoma/diagnóstico , Dermatofibrosarcoma/patología , Exones/genética , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Factor de Crecimiento Derivado de Plaquetas/genética , Estudios Retrospectivos , Neoplasias Cutáneas/patología , UniversidadesRESUMEN
Previous studies of oral microbiota by culture-dependent or targeted DNA approaches demonstrated that hyposalivation, a reduction in salivary secretions, might increase the amount of certain oral pathogens. However, the relationship between hyposalivation and the balance of oral microbiota, especially uncultivable bacteria, remains still unclear. The aim of this study was to elucidate the relationship between hyposalivation and oral microbiota by analyzing terminal restriction fragment length polymorphism (T-RFLP) of 16S rDNA. The 61 subjects were divided into two groups, hyposalivation group and normo-salivation group. The microbiota of tongue-coating samples was analyzed by T-RFLP. The amount of saliva, the number of Candida albicans, and also the dental status including plaque index, gingival index, bleeding on probing, probing pocket depth and decayed, missing, and filled teeth (DMFT) were assessed. Regarding the dental status, none of the evaluated factors were significantly different between the groups except the number of DMFT. According to the T-RFLP profiles, the patterns of microbiota in the tongue coating were classified into two groups, Clusters I and II. Cluster I is made up 76% of subjects with hyposalivation, while Cluster II is made up 61% of subjects with normo-salivation (p<0.001). Compared with the microbiota found in Cluster II, that in Cluster I had higher proportions of T-RFs corresponding to genera Veillonella, Dialister, Prevotella, Fusobacterium, and Streptococcus. T-RFLP analysis showed a significant role of salivary volume in determining the composition of the microbial community, regardless of the cultivability of the bacteria.
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Fenómenos Fisiológicos Bacterianos , Biodiversidad , Microbiota/genética , Polimorfismo de Longitud del Fragmento de Restricción , Xerostomía/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Bacterias/genética , Candida albicans/fisiología , ADN Ribosómico/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de Componente Principal , Saliva/química , Saliva/microbiología , Enfermedades Estomatognáticas/microbiología , Lengua/microbiologíaRESUMEN
OBJECTIVES: The toll-like receptor (TLR) family is thought to be expressed in many cell types in the skin and play a role in various diseases. The expression pattern and role of TLRs in systemic sclerosis (SSc) is to be clarified. We investigated the expression profiles of TLR-related genes in SSc fibroblasts, and tried to clarify their roles in the pathogenesis of this disease. METHODS: The expression profile of TLR-related genes was assessed by gene array. Real-time PCR was used to confirm the array result. The protein expression of TLRs and type I collagen was determined by immunoblotting and immunohistochemistry. RESULTS: PCR array revealed that several genes were up- or down-regulated in SSc fibroblasts compared to normal cells. Among them, both mRNA and protein levels of TLR5 and TLR10 were up-regulated in SSc fibroblasts. The transfection of Smad3 siRNA into SSc fibroblasts resulted in the down-regulation of TLR proteins. There was no significant difference in mRNA half-lives of TLR5 and TLR10 between normal and SSc fibroblasts. Immunohistochemical staining revealed that TLRs expression was strongly detected in SSc fibroblasts in vivo. The stimulation of TLR5 signal with flagellin reduced the expression of type I collagen in SSc fibroblasts, but not in normal fibroblasts. CONCLUSIONS: TLR5 and TLR10 expression is increased in SSc fibroblasts in vitro and in vivo, probably at transcript level via the TGF-ß/Smad3 activation. Furthermore, TLR5 itself may have suppressive effects on collagen expression, and its overexpression in SSc fibroblasts may be the negative feedback against tissue fibrosis.
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Colágeno Tipo I/metabolismo , Citocinas/genética , Fibroblastos/metabolismo , ARN Mensajero/metabolismo , Esclerodermia Sistémica/genética , Receptores Toll-Like/genética , Western Blotting , Células Cultivadas , Citocinas/metabolismo , Dermis/citología , Regulación hacia Abajo , Perfilación de la Expresión Génica , Humanos , Inmunohistoquímica , ARN Interferente Pequeño , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Esclerodermia Sistémica/metabolismo , Receptores Toll-Like/metabolismo , TransfecciónRESUMEN
AIM: The natural history and appropriate management of anastomotic sinus has not been clearly defined. The aim of this study was to evaluate the incidence, management and outcomes of anastomotic sinus. METHOD: The medical records of all patients who underwent a low anterior resection (LAR) or an ileal pouch-anal anastomosis (IPAA) with a diverting loop ileostomy (LI) and with contrast enema performed before planned stoma closure between 2001 and 2011 were retrospectively reviewed. The radiological features of the sinus tract, treatment and outcome of anastomotic sinus were studied. RESULTS: Twenty patients (8.2%) were found to have anastomotic sinuses out of the total of 244 patients who had undergone LAR (n = 146) or IPAA (n = 98) with LI. Of these, 13 (65%) had prior symptomatic leaks, while seven did not. Twelve patients (60%) were found to have simple sinus tracts, while eight had complex sinuses (associated with either pelvic cavities or severe strictures). Five patients with simple tracts were treated with observation alone. Fifteen patients underwent surgical interventions. Overall, with a median follow-up of 28 (6-73) months, 16 patients (80%) had resolution of their sinuses. All of 12 patients (100%) with simple sinus tracts and four of eight patients (50%) with complex sinuses underwent successful stoma reversals after 8 (3.5-24) months following the initial surgery (P = 0.01). CONCLUSION: Patients with simple tracts are significantly more likely to have complete resolution of sinuses than patients with complex sinuses. Persistent sinus associated with either a pelvic cavity or severe stricture despite surgical intervention is likely to lead to a permanent stoma.
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Canal Anal/cirugía , Anastomosis Quirúrgica , Reservorios Cólicos , Íleon/cirugía , Complicaciones Posoperatorias/terapia , Recto/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Fuga Anastomótica/etiología , Medios de Contraste , Enema , Femenino , Humanos , Ileostomía , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Adulto JovenRESUMEN
Linear IgA bullous disease (LABD) has been reported in association with inflammatory bowel disease, in particular ulcerative colitis (UC). We reporting a 34-year-old female who developed LABD during a flare-up of UC. We administered infliximab, which has been approved for the treatment of UC; infliximab dramatically improved the cutaneous lesions and bowel symptoms. This is the first report showing a marked effect of infliximab on LABD. First, we hypothesize that infliximab works for UC and then calms down excessive production of inflammatory cytokines and autoantibodies, and so stricter control of UC by infliximab is beneficial against the skin condition of LABD. Second, we suggest that TNF-α production in the lesion of LABD is increased, so TNF-α plays an important role in developing cutaneous lesions. This case suggests that infliximab, a monoclonal antibody against TNF-α, is efficacious in the cutaneous symptoms of LABD.