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1.
Medicina (Kaunas) ; 60(5)2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38793001

RESUMEN

Background and Objectives: In ampullary cancer, 5-year survival rates are 30-50%, even with optimal resection and perioperative systemic therapies. We sought to determine the important clinicopathological features and adjuvant treatments in terms of the prognosis of patients with operable-stage ampullary carcinomas. Materials and Methods: We included 197 patients who underwent pancreaticoduodenectomy to treat ampullary carcinomas between December 2003 and May 2019. Demographics, clinical features, treatments, and outcomes/survival were analyzed. Results: The median disease-free survival (mDFS) and median overall survival (mOS) were 40.9 vs. 63.4 months, respectively. The mDFS was significantly lower in patients with lymphovascular invasion (p < 0.001) and lymph node involvement (p = 0.027). Potential predictors of decreased OS on univariate analysis included age ≥ 50 years (p = 0.045), poor performance status (p = 0.048), weight loss (p = 0.045), T3-T4 tumors (p = 0.018), surgical margin positivity (p = 0.01), lymph node involvement (p = 0.001), lymphovascular invasion (p < 0.001), perineural invasion (p = 0.007), and poor histological grade (p = 0.042). For the multivariate analysis, only nodal status (hazard ratio [HR]1.98; 95% confidence interval [CI], 1.08-3.65; p = 0.027) and surgical margin status (HR 2.61; 95% CI, 1.09-6.24; p = 0.03) were associated with OS. Conclusions: Nodal status and a positive surgical margin were independent predictors of a poor mOS for patients with ampullary carcinomas. Additional studies are required to explore the role of adjuvant therapy in patients with ampullary carcinomas.


Asunto(s)
Ampolla Hepatopancreática , Neoplasias del Conducto Colédoco , Pancreaticoduodenectomía , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Ampolla Hepatopancreática/cirugía , Ampolla Hepatopancreática/patología , Pronóstico , Neoplasias del Conducto Colédoco/cirugía , Neoplasias del Conducto Colédoco/mortalidad , Neoplasias del Conducto Colédoco/patología , Pancreaticoduodenectomía/métodos , Adulto , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Análisis de Supervivencia
2.
Int Ophthalmol ; 43(8): 2917-2924, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36930361

RESUMEN

OBJECTIVE: To evaluate the efficacy of the toric intraocular lens (IOL) and capsular tension ring (CTR) suturing technique in eyes with long axial length (AL) with a high risk of toric IOL rotation. METHODS: This is a retrospective observational case series. The data files of patients who underwent a one-piece acrylic toric IOL (Tecnis Toric IOL and Acrysof IQ Toric IOL) implantation with the toric IOL and CTR suturing technique for cataract and astigmatism or toric IOL repositioning were analyzed. Inclusion criteria were a regular total corneal astigmatism of ≥ 1.5 D and an AL of ≥ 26.0 mm. Preoperative and postoperative astigmatism, uncorrected distance visual acuity (UDVA), IOL rotation, intraoperative, and postoperative complications were evaluated. RESULTS: A total of 30 eyes of 29 patients were included in this study. The mean AL was 27.82 ± 1.53 mm (range, 26.08-31.07). UDVA revealed a statistically significant improvement from 0.84 ± 0.20 logMAR preoperatively to 0.04 ± 0.06 logMAR postoperatively (p < 0.001). The mean preoperative corneal astigmatism was 3.08 ± 1.01 D reduced to the postoperative residual astigmatism of 0.59 ± 0.32 D which was found also statistically significant (p < 0.001). Only 2 eyes (6.2%) had postoperative toric IOL rotation of 5° and 10°, respectively. The mean degree of postoperative rotation was 0.50 ± 2.01. CONCLUSION: This technique provided excellent rotational stability even in eyes with longer AL and did not require additional intervention.


Asunto(s)
Astigmatismo , Catarata , Lentes Intraoculares , Facoemulsificación , Humanos , Astigmatismo/cirugía , Astigmatismo/complicaciones , Implantación de Lentes Intraoculares/métodos , Facoemulsificación/métodos , Agudeza Visual , Catarata/complicaciones , Refracción Ocular
3.
BMC Cancer ; 22(1): 516, 2022 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-35525929

RESUMEN

INTRODUCTION: Approximately 20-33% of all cancer patients are treated with acid-reducing agents (ARAs), most commonly proton pump inhibitors (PPIs), to reduce gastroesophageal reflux disease symptoms. Palbociclib and ribociclib are weak bases so their solubility depends on different pH. The solubility of palbociclib dramatically decreases to < 0.5 mg/ml when pH is above 4,5 but ribociclibs' solubility decreases when pH increases above 6,5. In the current study, we aimed to investigate the effects of concurrent PPIs on palbociclib and ribociclib efficacy in terms of progression-free survival in metastatic breast cancer (mBC) patients. PATIENTS AND METHODS: We enrolled hormone receptor-positive, HER2-negative mBC patients treated with endocrine treatment (letrozole or fulvestrant) combined palbociclib or ribociclib alone or with PPI accompanying our observational study. During palbociclib/ribociclib therapy, patients should be treated with "concurrent PPIs" defined as all or more than half of treatment with palbociclib/ribociclib, If no PPI was applied, it was defined as 'no concurrent PPI', those who used PPI but less than half were excluded from the study. All data was collected from real-life retrospectively. RESULTS: Our study included 217 patients, 105 of whom received palbociclib and 112 received ribociclib treatment. In the study population CDK inhibitor treatment was added to fulvestrant 102 patients ( 47%), to letrozole 115 patients (53%). In the Palbociclib arm fulvestrant/letrozole ratio was 53.3/46.7%, in the ribociclib arm it was 41.07/58.93%. Of 105 patients who received palbociclib, 65 were on concomitant PPI therapy, 40 were not. Of the 112 patients who received ribociclib, 61 were on concomitant PPI therapy, 51 were not. In the palbociclib group, the PFS of the patients using PPIs was shorter than the PFS of the patients not using (13.04 months vs. unreachable, p < 0.001). It was determined that taking PPIs was an independent predictor of shortening PFS (p < 0.001) in the multivariate analysis, In the ribociclib group, the PFS of the patients using PPIs was shorter than the PFS of the patients not using (12.64 months vs. unreachable, p = 0.003). It was determined that taking PPIs was single statistically independent predictor of shortening PFS (p = 0.003, univariate analysis). CONCLUSIONS: Our study demonstrated that concomitant usage of PPIs was associated with shorter PFS in mBC treated with both ribociclib and especially palbociclib. If it needs to be used, PPI selection should be made carefully and low-strength PPI or other ARAs (eg H2 antagonists, antacids) should be preferred.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Inhibidores de Proteínas Quinasas , Inhibidores de la Bomba de Protones , Aminopiridinas , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Interacciones Farmacológicas , Femenino , Fulvestrant , Humanos , Letrozol , Piperazinas , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de la Bomba de Protones/efectos adversos , Inhibidores de la Bomba de Protones/uso terapéutico , Purinas , Piridinas , Receptor ErbB-2/uso terapéutico , Estudios Retrospectivos
4.
Int J Gynecol Cancer ; 32(4): 502-507, 2022 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-35086927

RESUMEN

OBJECTIVE: Cisplatin-paclitaxel and bevacizumab is a frequently used treatment regimen for metastatic or recurrent cervical cancer, and carboplatin-paclitaxel and bevacizumab are also among the recommended regimens. In this study we aimed to evaluate the efficacy of these two regimens for the treatment of metastatic or recurrent cervical cancer. METHODS: Patients with metastatic or recurrent cervical cancer treated with cisplatin-paclitaxel and bevacizumab or carboplatin-paclitaxel and bevacizumab were retrospectively evaluated in this study. The clinical and demographic characteristics of patients in each group were evaluated. Median overall survival, progression-free survival, and response rates between the two groups were compared. RESULTS: A total of 250 patients were included. Overall, the numbers of patients with recurrent disease and metastatic disease were 159 and 91, respectively. The most common histologic subtype was squamous cell carcinoma (83.2%). The median duration of follow-up was 13.6 (range 0.5-86) months. The median progression-free survival was 10.5 (95% CI 9.0 to 11.8) months in the cisplatin-paclitaxel and bevacizumab group (group 1), and 10.8 (95% CI 8.6 to 13.0) months in the carboplatin-paclitaxel and bevacizumab group (group 2) (HR 1.20; 95% CI 0.88 to 1.63; p=0.25). The median overall survival was 19.1 (95% CI 13.0 to 25.1) months in group 1 and 18.3 (95% CI 15.3 to 21.3) months in group 2 (HR 1.28; 95% CI 0.91 to 1.80; p=0.15). CONCLUSIONS: There is no survival difference between cisplatin or carboplatin combined with paclitaxel and bevacizumab in metastatic or recurrent cervical cancer.


Asunto(s)
Cisplatino , Neoplasias del Cuello Uterino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/uso terapéutico , Carboplatino/efectos adversos , Cisplatino/uso terapéutico , Femenino , Humanos , Recurrencia Local de Neoplasia/patología , Paclitaxel/efectos adversos , Estudios Retrospectivos , Neoplasias del Cuello Uterino/patología
5.
N Engl J Med ; 372(16): 1510-8, 2015 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-25875256

RESUMEN

BACKGROUND: Oral ulcers, the hallmark of Behçet's syndrome, can be resistant to conventional treatment; therefore, alternative agents are needed. Apremilast is an oral phosphodiesterase-4 inhibitor that modulates several inflammatory pathways. METHODS: We conducted a phase 2, multicenter, placebo-controlled study in which 111 patients with Behçet's syndrome who had two or more oral ulcers were randomly assigned to receive 30 mg of apremilast twice daily or placebo for 12 weeks. This regimen was followed by a 12-week extension phase in which the placebo group was switched to apremilast and a 28-day post-treatment observational follow-up phase. The patients and clinicians were unaware of the study assignments throughout the trial. The primary end point was the number of oral ulcers at week 12. Secondary outcomes included pain from these ulcers (measured on a 100-mm visual-analogue scale, with higher scores indicating worse pain), the number of genital ulcers, overall disease activity, and quality of life. RESULTS: The mean (±SD) number of oral ulcers per patient at week 12 was significantly lower in the apremilast group than in the placebo group (0.5±1.0 vs. 2.1±2.6) (P<0.001). The mean decline in pain from oral ulcers from baseline to week 12 was greater with apremilast than with placebo (-44.7±24.3 mm vs. -16.0±32.5 mm) (P<0.001). Nausea, vomiting, and diarrhea were more common in the apremilast group (with 22, 9, and 12 incidents, respectively, among 55 patients) than in the placebo group (with 10, 1, and 2 incidents, respectively, among 56 patients), findings that were similar to those in previous studies of apremilast. There were two serious adverse events in patients receiving apremilast. CONCLUSIONS: Apremilast was effective in treating oral ulcers, which are the cardinal manifestation of Behçet's syndrome. This preliminary study was neither large enough nor long enough to assess long-term efficacy, the effect on other manifestations of Behçet's syndrome, or the risk of uncommon serious adverse events. (Funded by Celgene; ClinicalTrials.gov number, NCT00866359.).


Asunto(s)
Síndrome de Behçet/tratamiento farmacológico , Úlceras Bucales/tratamiento farmacológico , Inhibidores de Fosfodiesterasa 4/uso terapéutico , Talidomida/análogos & derivados , Adulto , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/uso terapéutico , Área Bajo la Curva , Síndrome de Behçet/complicaciones , Método Doble Ciego , Femenino , Enfermedades de los Genitales Femeninos/tratamiento farmacológico , Enfermedades de los Genitales Masculinos/tratamiento farmacológico , Humanos , Masculino , Úlceras Bucales/etiología , Inhibidores de Fosfodiesterasa 4/efectos adversos , Talidomida/efectos adversos , Talidomida/uso terapéutico
6.
Oral Health Prev Dent ; 16(6): 541-547, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30574608

RESUMEN

PURPOSE: Gestational diabetes mellitus (GDM) is defined as glucose intolerance with first onset or diagnosis in pregnancy. This study evaluated clinical and biochemical parameters in a possible association between GDM and gingival inflammation. MATERIALS AND METHODS: A total of 87 pregnant women - 44 with GDM and 43 without (NGDM) - were included. Subgroups were created according to gingival inflammation. Plaque index (PI), bleeding on probing (BOP), and probing depth (PD) were recorded. RESULTS: Age, anthropometric variables and baby weight (g) were all statistically significantly higher in the GDM group (p < 0.0001). Systolic and diastolic blood pressure (mmHg), saliva, serum leptin and adiponectin levels were similar in the GDM and NGDM groups (p = 0.605, p = 0.662, p = 0.737, and p = 0.596, respectively). Salivary adiponectin levels were statistically significantly higher in the two subgroups with gingivitis compared to those with clinically healthy periodontium (p < 0.01). Serum adiponectin levels were statistically significantly higher in the NGDM subgroup with gingivitis than the NGDM group with clinically healthy periodontium (p < 0.05). Statistically significant positive correlations were found between PD, PI, BOP and saliva adiponectin levels in the GDM group (p < 0.05). Positive correlations were also found between clinical periodontal parameters and saliva, serum levels of adiponectin in the control group without GDM (p < 0.05). CONCLUSION: The higher salivary adiponectin levels in the gingivitis groups suggest that gingival inflammation is more likely to influence local inflammatory parameters both in the presence and absence of GDM. Further larger-scale studies are required to better clarify the possible interactions between gingival inflammation and GDM.


Asunto(s)
Adiponectina/análisis , Diabetes Gestacional/metabolismo , Gingivitis/metabolismo , Leptina/análisis , Saliva/química , Adiponectina/sangre , Adulto , Diabetes Gestacional/sangre , Femenino , Humanos , Leptina/sangre , Embarazo
7.
Cutan Ocul Toxicol ; 36(1): 5-8, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26911396

RESUMEN

OBJECTIVE: To investigate the effect and safety of intravitreal injection (IVI) of bevacizumab and ranibizumab on corneal endothelial cell count and morphology in patients with diabetic macular edema. MATERIALS AND METHODS: A total of 60 eyes from 60 consecutive patients who received 0.5 mg/0.05 ml IVIs of bevacizumab (n = 30, IVB group) or 1.25 mg/0.05 ml ranibizumab (n = 30, IVR group) for three consecutive months were investigated prospectively. Specular microscopy was performed to evaluate endothelial cell count, the percentage of hexagonal cells (pleomorphism), and the coefficient of variation of the cell size (polymegathism); optical biometry was performed to evaluate central corneal thickness. Results before injection and 1 month after the first and third injections were compared. RESULTS: The groups were matched for age (p = 0.11) and gender (p = 0.32). There was no significant difference in endothelial cell count (IVB group, p = 0.66; IVR group, p = 0.74), pleomorphism (IVB group, p = 0.44; IVR group, p = 0.88) and polymegathism (IVB group, p = 0.21; IVR group, p = 0.24) before injection or 1 month after the first and third injections. There was also no difference in central corneal thickness (IVB group, p = 0.15; IVR group, p = 0.58) before injection or 1 month after the first and third injections. CONCLUSION: Monthly 1.25 mg/0.05 ml IVIs of bevacizumab or 0.5 mg/0.05 ml of ranibizumab for three consecutive months in the treatment of diabetic macular edema does not affect corneal morphology and has no harmful effects on the endothelium.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Bevacizumab/uso terapéutico , Retinopatía Diabética/tratamiento farmacológico , Endotelio Corneal/efectos de los fármacos , Edema Macular/tratamiento farmacológico , Ranibizumab/uso terapéutico , Anciano , Inhibidores de la Angiogénesis/administración & dosificación , Bevacizumab/administración & dosificación , Endotelio Corneal/anatomía & histología , Endotelio Corneal/citología , Femenino , Humanos , Inyecciones Intravítreas , Masculino , Persona de Mediana Edad , Ranibizumab/administración & dosificación
8.
J Clin Periodontol ; 42(6): 506-12, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25959628

RESUMEN

AIM: Gestational diabetes mellitus (GDM), gingivitis, infection with specific periodontal pathogens and systemic inflammation each increase the risk for poor pregnancy outcome. We set out to monitor the interactions of gingivitis and GDM with respect to oral infection and the systemic inflammatory burden. MATERIALS AND METHODS: Four case-control groups (n = 117) were recruited, (1) No gingivitis, No GDM (n = 27); (2) Gingivitis, No GDM (n = 31); (3) No gingivitis, GDM (n = 21); and (4) Gingivitis, GDM (n = 38). Oral infection with three key periodontal pathogens was determined by PCR. Systemic inflammation was determined by quantification of CRP by EIA. RESULTS: Gingivitis during pregnancy was associated with oral infection with Porphyromonas gingivalis, Filifactor alocis and Treponema denticola and combinations thereof (all p < 0.01). GDM was also associated with increased infection with individual and multiple oral pathogens (all p < 0.05). Gingivitis during pregnancy led to a 325% increase in systemic CRP (mean, 2495 versus 8116 ng/ml, p < 0.01). CONCLUSIONS: Diabetes and gingivitis act in concert to increase risk biomarkers for poor pregnancy outcome.


Asunto(s)
Diabetes Gestacional/microbiología , Gingivitis/microbiología , Complicaciones Infecciosas del Embarazo/microbiología , Adulto , Bacterias Anaerobias/aislamiento & purificación , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Cotinina/análisis , Índice de Placa Dental , Diabetes Gestacional/sangre , Femenino , Gingivitis/sangre , Bacterias Grampositivas/aislamiento & purificación , Humanos , Índice Periodontal , Bolsa Periodontal/clasificación , Porphyromonas gingivalis/aislamiento & purificación , Embarazo , Complicaciones Infecciosas del Embarazo/sangre , Resultado del Embarazo , Saliva/química , Saliva/microbiología , Treponema denticola/aislamiento & purificación , Adulto Joven
9.
Endocr Res ; 39(2): 56-60, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24067097

RESUMEN

INTRODUCTION: The aim of the present study was to investigate the reference intervals for thyroid stimulating hormone (TSH) in healthy individuals with normal levels of serum free thyroxine (fT4) and without sonographic pathologies, and determine the effects of age, gender, and residence on the TSH reference intervals. SUBJECTS AND METHODS: This research was a population-based study conducted in 70 regions. The random sampling method was used to select the 1095 subjects of the study among inhabitants aged 18 and above. Patients who had a previous history of thyroid disease and had been taking medication were excluded from the study as this may have affected their fT4 or TSH levels. In addition, subjects who had serum fT4 without a reference range and abnormal ultrasonography findings were also excluded. A total of 408 subjects were used for establishing the reference intervals for TSH. RESULTS: The data for TSH in the study group were not normally distributed according to the Kolmogorov-Smirnov index. The geometric mean was 1.62 mIU/L, the median was 1.40 mIU/L, and the 95% reference intervals were 0.38-4.22 mIU/L. The median TSH level was higher in females compared to males (p < 0.05). In the female subjects 2.5th percentile of TSH was lower and 97.5th percentile was higher than those of males. The reference intervals of TSH were of lower values in subjects over 50 years old (p < 0.001). DISCUSSION: Studies suggest that determination of the TSH reference intervals may differ due to environmental influences or due to age, gender, and race. It is suggested that the lower limit of normal TSH for the adult Turkish population would be 0.38 mIU/L and the upper limit similar to the traditional value of 4.2 mIU/L. If each clinician uses their population-specific reference interval for TSH, thyroid function abnormalities can be accurately estimated.


Asunto(s)
Química Clínica/normas , Glándula Tiroides/diagnóstico por imagen , Tirotropina/sangre , Tiroxina/sangre , Adolescente , Adulto , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , Estadísticas no Paramétricas , Turquía , Ultrasonografía , Adulto Joven
10.
Expert Opin Pharmacother ; 25(11): 1555-1563, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39115275

RESUMEN

OBJECTIVES: We aimed to evaluate the efficacy and safety of granulocyte-colony stimulating factor (G-CSF) prophylaxis during chemoimmunotherapy with carboplatin plus etoposide and atezolizumab in extensive-stage small cell lung cancer (ES-SCLC). METHODS: This retrospective, multicenter study enrolled ES-SCLC patients receiving carboplatin plus etoposide and atezolizumab, categorized into G-CSF and non-G-CSF groups. Demographic and disease-related data were collected. Response rates, progression-free survival (PFS), overall survival (OS), and toxicity were analyzed. RESULTS: Of 119 patients (median age: 63 years), the overall response rate (ORR) and disease control rate (DCR) were 72.3% and 81.5%, respectively. In the G-CSF group, the ORR was 76.4% compared to 60.0% in the non-G-CSF group (p = 0.33), and the DCR was 85.4% versus 70.0%, respectively (p = 0.46). Median PFS was 8.3 months (95% CI, 6.8-9.8) in the G-CSF group and 6.8 months (95% CI, 6.2-7.5) in the non-G-CSF group (p = 0.24). Median OS was 13.8 months (95% CI, 9.6-18.1) for the G-CSF group and 10.6 months (95% CI, 7.9-13.3) for the non-G-CSF group (p = 0.47). Grade 3 ≥ adverse events were similar between groups (49.4% vs. 33.3%, respectively, p = 0.12). CONCLUSION: G-CSF prophylaxis can be safely used in ES-SCLC patients undergoing carboplatin plus etoposide and atezolizumab regimen without significantly altering efficacy or increasing toxicity.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Carboplatino , Etopósido , Factor Estimulante de Colonias de Granulocitos , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Masculino , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Carboplatino/uso terapéutico , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/patología , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Etopósido/administración & dosificación , Etopósido/efectos adversos , Etopósido/uso terapéutico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Adulto , Inmunoterapia/métodos , Supervivencia sin Progresión , Anciano de 80 o más Años , Tasa de Supervivencia , Estadificación de Neoplasias , Resultado del Tratamiento
11.
J Chemother ; : 1-12, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39257075

RESUMEN

Non-clear cell renal cell carcinoma (non-ccRCC) is a highly heterogeneous disease group, accounting for approximately 25% of all RCC cases. Due to its rarity and especially heterogeneity, phase III trial data is limited and treatment options generally follow those of clear cell RCC. In the literature, there exists a number of studies with sunitinib, cabozantinib, and everolimus, but data on the efficacy of pazopanib are limited. Our aim in this study was to compare the efficacy of pazopanib and sunitinib, in a multicenter retrospective cohort of non-ccRCC patients. Our study included patients diagnosed with non-ccRCC who received pazopanib or sunitinib treatment as first-line therapy from 22 tertiary hospitals. We compared the progression-free survival (PFS), overall survival (OS), and response rates of pazopanib and sunitinib treatments. Additionally, we investigated prognostic factors in non-ccRCC. PFS and response rates of sunitinib and pazopanib were found to be similar, while a numerical difference was observed in OS. Being 65 years and older, being in the intermediate or poor risk group according to the International Metastatic Renal Cell Carcinoma Database Consortium, having liver metastases, presence of a sarcomatoid component, and having de novo metastatic disease were found to be significantly associated with shorter PFS. Pazopanib treatment appears to have similar efficacy in the treatment of non-ccRCC compared to sunitinib. Though randomized controlled trials are lacking and will probably be never be available, we suggest that pazopanib could be a preferred agent like sunitinib and cabozantinib.


Pazopanib and sunitinib treatments show similar progression free survival, overall survival and objective response rate.IMDC risk group, liver metastasis, sarcomatoid component and de novo metastatic disease were determined as prognostic factors.

12.
J Chemother ; : 1-7, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38497444

RESUMEN

The only phase 3 study on the effectiveness of CDK 4-6 inhibitors in first-line treatment in premenopausal patients with hormone receptor (HR) positive, HER2 negative metastatic breast cancer is the MONALEESA-7 study, and data on the effectiveness of palbociclib is limited. Data are also limited regarding the effectiveness of CDK 4-6 inhibitors in patients whose dose was reduced due to neutropenia, the most common side effect of CDK 4-6 inhibitors. In our study, we aimed to evaluate the effectiveness of palbociclib and ribociclib in first-line treatment in patients with premenopausal metastatic breast cancer and the effect of dose reduction due to neutropenia on progression-free survival. Our study is a multicenter, retrospective study, and factors affecting progression-free survival (PFS) were examined in patients diagnosed with metastatic premenopausal breast cancer from 29 different centers and receiving combination therapy containing palbociclib or ribociclib in the metastatic stage. 319 patients were included in the study. The mPFS for patients treated with palbociclib was 26.83 months, and for those receiving ribociclib, the mPFS was 29.86 months (p = 0.924). mPFS was 32.00 months in patients who received a reduced dose, and mPFS was 25.96 months in patients who could take the initial dose, and there was no statistical difference (p = 0.238). Liver metastasis, using a fulvestrant together with a CDK 4-6 inhibitor, ECOG PS 1 was found to be a negative prognostic factor. No new adverse events were observed. In our study, we found PFS over 27 months in patients diagnosed with premenopausal breast cancer with CDK 4-6 inhibitors used in first-line treatment, similar to post-menopausal patients. We did not detect any difference between the effectiveness of the two CDK 4-6 inhibitors, and we showed that there was no decrease in the effectiveness of the CDK 4-6 inhibitor in patients whose dose was reduced due to neutropenia.

13.
Am J Hum Genet ; 86(5): 797-804, 2010 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-20451170

RESUMEN

More than 270 million people worldwide have hearing loss that affects normal communication. Although astonishing progress has been made in the identification of more than 50 genes for deafness during the past decade, the majority of deafness genes are yet to be identified. In this study, we mapped a previously unknown autosomal-recessive nonsyndromic sensorineural hearing loss locus (DFNB91) to chromosome 6p25 in a consanguineous Turkish family. The degree of hearing loss was moderate to severe in affected individuals. We subsequently identified a nonsense mutation (p.E245X) in SERPINB6, which is located within the linkage interval for DFNB91 and encodes for an intracellular protease inhibitor. The p.E245X mutation cosegregated in the family as a completely penetrant autosomal-recessive trait and was absent in 300 Turkish controls. The mRNA expression of SERPINB6 was reduced and production of protein was absent in the peripheral leukocytes of homozygotes, suggesting that the hearing loss is due to loss of function of SERPINB6. We also demonstrated that SERPINB6 was expressed primarily in the inner ear hair cells. We propose that SERPINB6 plays an important role in the inner ear in the protection against leakage of lysosomal content during stress and that loss of this protection results in cell death and sensorineural hearing loss.


Asunto(s)
Codón sin Sentido , Pérdida Auditiva Sensorineural/genética , Pérdida Auditiva/genética , Mutación , Serpinas/genética , Consanguinidad , Familia , Herencia , Homocigoto , Humanos
14.
Nat Genet ; 35(4): 318-21, 2003 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-14595441

RESUMEN

Congenital fibrosis of the extraocular muscles type 1 (CFEOM1; OMIM #135700) is an autosomal dominant strabismus disorder associated with defects of the oculomotor nerve. We show that individuals with CFEOM1 harbor heterozygous missense mutations in a kinesin motor protein encoded by KIF21A. We identified six different mutations in 44 of 45 probands. The primary mutational hotspots are in the stalk domain, highlighting an important new role for KIF21A and its stalk in the formation of the oculomotor axis.


Asunto(s)
Variación Genética , Cinesinas/genética , Mutación/genética , Proteínas del Tejido Nervioso/genética , Músculos Oculomotores/patología , Oftalmoplejía/congénito , Secuencia de Aminoácidos , Niño , Femenino , Fibrosis , Ligamiento Genético , Heterocigoto , Humanos , Masculino , Datos de Secuencia Molecular , Oftalmoplejía/patología , Linaje , Fenotipo , Homología de Secuencia de Aminoácido
15.
Indian J Pathol Microbiol ; 65(2): 321-327, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35435366

RESUMEN

Context: HER2-targeted therapy has been shown to benefit HER2-positive gastric cancer. It is very important to determine the HER2 expression level correctly to select the appropriate test and sampling method. Aim: In this study, we investigated the frequency of overexpression of HER2 and intratumoral heterogeneity of HER2-positive cases, comparison of HER2 used immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) performance in biopsy and resection specimens, the correlation of HER2 status between biopsy and resection specimens, and its relationship with clinicopathological findings. Materials and Methods: Formalin-fixed, paraffin-embedded specimens of a total of 40 surgically resected and biopsy specimens of gastric cancer were analyzed. HER2 status was examined using both IHC and FISH techniques, and the findings and their association with different clinicopathological parameters were evaluated. Results: The concordance rate between the results of IHC and FISH in biopsy and resection specimens was 96.6% and 86.6%, respectively. In paired 20 cases, the overall concordance rate of HER2-IHC and HER2-FISH status between biopsy and resection specimens was 90% and 100%, respectively. HER2-IHC analysis revealed that 5/40 cases were IHC 2+ and only 1 of 5 IHC 2+ cases demonstrated HER2-FISH amplification. Conclusion: Our results showed that HER2-IHC was well concordant with FISH in cases with a score of 0/1+ or 3+ and demonstrates strong concordance between biopsy and resection specimens. FISH should be performed when the IHC result is equivocal. In our study, no statistically significant correlation was observed between HER2 positivity and clinicopathological parameters. Overall, both biopsy and resection specimens are appropriate for HER2 testing.


Asunto(s)
Neoplasias de la Mama , Carcinoma , Neoplasias Gástricas , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Biopsia , Femenino , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Receptor ErbB-2/análisis , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética
16.
Turk J Ophthalmol ; 52(1): 14-22, 2022 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-35196835

RESUMEN

Objectives: This study evaluated acoustic biofeedback training using microperimetry in patients with foveal scars and an eligible retinal locus for better fixation. Materials and Methods: A total of 29 eligible patients were enrolled in the study. The acoustic biofeedback training module in the MAIA (Macular Integrity Assessment, CenterVue®, Italy) microperimeter was used for training. To determine the treatment efficacy, the following variables were compared before and after testing: best corrected visual acuity (BCVA); MAIA microperimeter full threshold 4-2 test parameters of average threshold value, fixation parameters P1 and P2, and bivariate contour ellipse area (BCEA) for 63% and 95% of fixation points; contrast sensitivity (CSV 1000E Contrast Sensitivity Test); reading speed using the Minnesota Low-Vision Reading Test (MNREAD reading chart); and quality of life (NEI-VFQ-25). In addition, fixation stability parameters were recorded during each session. Results: The study group consisted of 29 patients with a mean age of 68.72±8.34 years. Median BCVA was initially 0.8 (0.2-1.6) logMAR and was 0.8 (0.1-1.6) logMAR after 8 weeks of preferred retinal locus training (p=0.003). The fixation stability parameter P1 improved from a mean of 21.28±3.08% to 32.69±3.69% (p=0.001) while mean P2 improved from 52.79±4.53% to 68.31±3.89% (p=0.001). Mean BCEA 63% decreased from 16.11±2.27°2 to 13.34±2.26°2 (p=0.127) and mean BCEA 95% decreased from 45.87±6.72°2 to 40.01±6.78°2 (p=0.247) after training. Binocular reading speed was 38.28±6.25 words per minute (wpm) before training and 45.34±7.35 wpm after training (p<0.001). Statistically significant improvement was observed in contrast sensitivity and quality of life questionnaire scores after training. Conclusion: Beginning with the fifth session, biofeedback training for a new trained retinal locus improved average sensitivity, fixation stability, reading speed, contrast sensitivity, and quality of life in patients with macular scarring.


Asunto(s)
Baja Visión , Campos Visuales , Anciano , Fijación Ocular , Humanos , Persona de Mediana Edad , Calidad de Vida , Agudeza Visual
17.
J Oncol Pharm Pract ; 17(3): 285-7, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20551113

RESUMEN

Tyrosine kinase inhibitors (TKIs) are targeted treatments for various cancers. Skin toxicities are one of the most common nonhematological side-effects of TKIs. We report an imatinib mesylate (IM) induced hyperpigmented acne rosacea (AR) and sunitinib-induced palmar hyperkeratosis in the case with gastrointestinal stromal tumor. AR was arisen due to the discontinuation of IM. To the best of our knowledge, this kind of cutaneous side-effect with IM has not been documented previously.


Asunto(s)
Antineoplásicos/efectos adversos , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Neoplasias Intestinales/tratamiento farmacológico , Piperazinas/efectos adversos , Inhibidores de Proteínas Quinasas/efectos adversos , Pirimidinas/efectos adversos , Rosácea/inducido químicamente , Piel/efectos de los fármacos , Inhibidores de la Angiogénesis/efectos adversos , Benzamidas , Biopsia , Tumores del Estroma Gastrointestinal/enzimología , Tumores del Estroma Gastrointestinal/patología , Antagonistas de los Receptores Histamínicos/uso terapéutico , Humanos , Hiperpigmentación/inducido químicamente , Hiperpigmentación/patología , Mesilato de Imatinib , Indoles/efectos adversos , Neoplasias Intestinales/enzimología , Neoplasias Intestinales/patología , Queratodermia Palmoplantar/inducido químicamente , Queratodermia Palmoplantar/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/metabolismo , Pirroles/efectos adversos , Rosácea/tratamiento farmacológico , Rosácea/patología , Piel/patología , Pigmentación de la Piel/efectos de los fármacos , Sunitinib , Resultado del Tratamiento
18.
Arch Gynecol Obstet ; 284(2): 405-9, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20872226

RESUMEN

BACKGROUND: Non-Hodgkin lymphomas of the breast are uncommon cancers that occur as either primary extranodal diseases or secondary localizations of a systemic disease. The term "primary breast lymphoma" (PBL) is used to define malignant lymphomas primarily occurring in the breast in the absence of previously detected lymphoma localizations. In this report, we analyzed nine patients with primary diffuse large B cell lymphoma (DLBCL) of breast. PATIENTS AND METHODS: Patients with newly diagnosed PBLs treated between 1997 and 2009 in five institutions were retrospectively evaluated. RESULTS: The median age of the patients with PBL was 49 years (range 30-82 years), and four patients had left-sided and five had right-sided disease. All of the nine patients were classified as DLBCL. Five patients with DLBCL received chemotherapy followed by involved-field or elective-field radiotherapy and four received chemotherapy alone. Complete remission (CR) following primary treatment for all patients with PBL except for two cases was obtained. In two patients, recurrence occurred. At the median follow-up of 24.2 months, the 5-year OS rate was 76.2%. Univariate analysis indicated that age, ECOG PS, clinical stage, international prognostic index score, lactate dehydrogenase levels and the presence of B symptoms were not important prognostic factors in our study. CONCLUSIONS: Our series contained a small sample size, but it is interesting because it included only DLBCL cases. However, definitive conclusions about treatment and follow-up options of patients cannot be made in such a small series of patients. There are very few reports of patients with PBL treated with R-CHOP rather than CHOP alone. The followup is probably still too short and sample size very few to know how R-CHOP compares with CHOP-treated patients in other series, but this is definitely worth looking at in more detail when reasonable median follow-up has been achieved and sample size are sufficient.


Asunto(s)
Neoplasias de la Mama/patología , Linfoma de Células B Grandes Difuso/patología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/sangre , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/radioterapia , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Estimación de Kaplan-Meier , L-Lactato Deshidrogenasa/sangre , Linfoma de Células B Grandes Difuso/sangre , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/radioterapia , Persona de Mediana Edad , Prednisona/administración & dosificación , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Rituximab , Resultado del Tratamiento , Vincristina/administración & dosificación
19.
Indian J Ophthalmol ; 69(2): 301-306, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33463578

RESUMEN

Purpose: The study aimed to investigate the changes in choroidal thickness (CT), retinal nerve fiber layer thickness (RNFL), and visual field parameters in morbidly obese patients following bariatric surgery. Methods: The study included 40 morbidly obese patients with body mass indexes (BMI) ≥40 who had undergone bariatric surgery (Group 1) and 40 age-and sex-matched healthy subjects with normal BMI values (Group 2). RNFL and CT measurements by optical coherence tomography (OCT) and visual field test were performed preoperatively and the 1st, 6th, and 12th months postoperatively. CT measurements were obtained from the subfoveal, nasal (N), and temporal (T) regions at distances of 500 µm and 1,000 µm from the fovea. Results: No significant pathology was detected during ophthalmological examinations following bariatric surgery. The BMIs were found to be significantly lower in all of the periods after bariatric surgery (P < 0.0001). The CT measurements decreased significantly in all periods after bariatric surgery (P < 0.0001). No differences were found in terms of the mean RNFL thicknesses in all postoperative periods (P = 0.125). Visual field tests showed no significant changes during scheduled visits. (P = 0.877). No visual field defect was detected in any patient during the follow-up periods after bariatric surgery. Conclusion: These results have suggested that CT is positively correlated with BMI and decreased with a reduction in BMI progressively. Nutritional disorders resulting from malabsorption have not caused any nutritional optic neuropathy and visual field defect for at least the first postoperative year after bariatric surgery.


Asunto(s)
Cirugía Bariátrica , Obesidad Mórbida , Coroides/diagnóstico por imagen , Humanos , Fibras Nerviosas , Obesidad Mórbida/cirugía , Tomografía de Coherencia Óptica , Campos Visuales
20.
Cancer Invest ; 28(1): 33-7, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19995229

RESUMEN

BACKGROUND: Treatment of patients with metastatic colorectal cancer (MCRC) previously exposed to oxaliplatin-based regimen is challenging. Efficacy and toxicity of bevacizumab plus irinotecan-based regimens were assessed in the second-line treatment of MCRC patients. PATIENTS AND METHODS: Forty patients with a median age of 53 years (range, 31-75) were retrospectively evaluated. Patients progressing or relapsing after treatment with oxaliplatin-based regimens were given bevacizumab 5 mg/kg every 2 weeks in combination with irinotecan-based regimens. All patients had previously received oxaliplatin either in the adjuvant setting (n = 8) or for metastatic disease (n = 32). RESULTS: Three patients achieved a complete response (7.5%), 5 partial responses (12.5%) and 14 (35%) stable disease resulting in an overall response rate of 20%. Median progression-free survival was 6 months (95% CI, 4.0-8.0) with a median overall survival of 14 months (95% CI, 10.2-17.8). One-year survival rate was 55.9%. Grade 3-4 toxicities were as follows: neutropenia (n = 15, 37.5%), febrile neutropenia (n = 2, 5%), diarrhea (n = 11, 27.5%), nausea and vomiting (n = 3, 7.5%), gastrointestinal perforation (n = 2, 5%), and thromboembolism (n = 2, 5%). CONCLUSION: Bevacizumab plus irinotecan-based combination chemotherapy is an active and safe treatment option in patients failing oxaliplatin-based therapy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adulto , Anciano , Inhibidores de la Angiogénesis/administración & dosificación , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Quimioterapia Adyuvante , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/secundario , Progresión de la Enfermedad , Femenino , Humanos , Irinotecán , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Estudios Retrospectivos , Factores de Tiempo , Insuficiencia del Tratamiento
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