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1.
South Asian J Cancer ; 12(4): 378-383, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38130284

RESUMO

Prutha Jinwala T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) in adolescents and young adults (AYAs) is a clinically aggressive malignancy and life-threatening at diagnosis. Intensive chemotherapy protocols, inspired by the Berlin-Frankfurt-Münster (BFM) regimen, along with central nervous system (CNS) prophylaxis, have achieved a 75 to 85% 5-year disease-free survival rate. However, in cases of marrow and CNS relapses, second-line chemotherapy is usually ineffective. This study aimed to assess the safety and efficacy of the BFM 2002 protocol and to correlate clinical profiles and prognostic factors with survival outcomes in AYA T-ALL/LBL patients. We retrospectively analyzed data from T-ALL/LBL patients treated at the Department of Medical Oncology, Sri Aurobindo Institute of Medical Sciences (SAIMS), Indore, between 2018 and 2021. Twenty-one patients aged 15 to 29 years were studied for their clinical course and laboratory parameters over 36 months. Diagnosis and risk stratification were performed following the guidelines of the BFM 2002 protocol. All patients received treatment and monitoring according to this pediatric-inspired protocol. The median age of the patients was 17 years (range: 15-28 years). Eleven patients presented with mediastinal lymph node enlargement, 10% exhibited CNS involvement, and none had testicular involvement. Eleven patients had marrow blasts greater than 25%, indicative of acute lymphoblastic leukemia. All 21 patients were treated according to the intensive modified BFM 2002 protocol and achieved morphological remission after a median follow-up of 24 months (range: 18-36 months). Seventeen patients achieved minimal residual disease (MRD) negativity post-induction. MRD at day 33 showed a significant association with the probability of disease relapse ( p = 0.0015). There were five deaths (24%), one due to toxicity and four due to relapse. The study recorded an 18-month overall survival of 76%. These results were achieved despite financial constraints. Data were entered into a spreadsheet, and statistical analysis was performed using IBM SPSS version 23. Continuous data are presented as ranges and medians, while categorical variables are shown as percentages and numbers. A chi-squared test for association, with a significance level set at p < 0.05, was conducted as indicated. AYA T-ALL/LBL requires intensive treatment regimens. With biological characterization of LBL/ALL and close therapy monitoring, encouraging outcomes can be achieved even in resource-limited settings.

2.
Brachytherapy ; 22(6): 753-760, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37716821

RESUMO

PURPOSE: To evaluate clinical outcomes of recurrent gynaecological cancers treated with reirradiation (reRT) using advanced brachytherapy (BT) technique. METHODS AND MATERIALS: Seventy-six women who underwent reRT with BT for gynaecological cancers at our institute between January 2000 and December 2019 were analysed to determine patient, disease and treatment characteristics and clinical outcomes. Descriptive analysis was used for demographics, and the Kaplan Meir method was used for survival analysis. RESULTS: Median age at recurrence was 55 years (Range: 35-73). Forty-three patients had recurrent cervical cancer with intact uterus, and 33 had recurrent vault/vaginal cancers post adjuvant RT. Eight patients received EBRT prior to BT (Range: 30-50Gy). Twenty-two patients (28.9%) received salvage chemotherapy before consideration of brachytherapy. Brachytherapy application was done using MUPIT in 38, Vienna applicator in 20, Syed Neblett in 8, central vaginal cylinder in 3, multicatheter intravaginal applicator in 2, tandem-ovoids in 4 and Houdek applicator in 1 patient. Median cumulative EQD2 for all courses of radiation was 108 Gy (IQR 92-123 Gy). At median follow up of 39 months, local control (LC), progression-free survival (PFS) and Overall survival (OS) at 2-years was 60%, 56.3%, and 72.9 respectively. Patients who had recurrences beyond 2 years had significantly better OS compared to early recurrences. Patients who received BT doses >40 Gy had a higher LC and PFS. Grade 3 to 4 late rectal toxicity was seen in 10 (13%), bladder toxicity in 6 (8%) and vaginal fibrosis in 24 (31%) patients. CONCLUSION: The use of advanced BT approach in reirradiation setting is a feasible and safe option in treatment of post-treatment recurrent cervical, endometrial, and vaginal cancers.


Assuntos
Braquiterapia , Neoplasias dos Genitais Femininos , Reirradiação , Neoplasias Vaginais , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias Vaginais/radioterapia , Braquiterapia/métodos , Dosagem Radioterapêutica , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/etiologia
3.
Malar J ; 22(1): 62, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36810077

RESUMO

BACKGROUND: Global malaria cases rose by 14 million, and deaths by 69,000, in 2020. In India, a 46% decline has been reported between 2020 and 2019. In 2017, the Malaria Elimination Demonstration Project conducted a needs-assessment of the Accredited Social Health Activists (ASHAs) of Mandla district. This survey revealed the inadequate level of knowledge in malaria diagnosis and treatment. Subsequently, a training programme was launched for enhancing malaria-related knowledge of ASHAs. The present study was conducted in 2021 to evaluate the impact of training on malaria-related knowledge and practices of ASHAs in Mandla. This assessment was also done in two adjoining districts: Balaghat and Dindori. METHODS: A cross-sectional survey using a structured questionnaire was administered to ASHAs to measure their knowledge and practices related to malaria etiology, prevention, diagnosis, and treatment. A comparison of information collected from these three districts was performed using simple descriptive statistics, comparison of means and multivariate logistic regression analysis. RESULTS: Significant improvement was noted amongst ASHAs of district Mandla between 2017 (baseline) and 2021 (endline) in knowledge related to malaria transmission, preventive measures, adherence to the national drug policy, diagnosis using rapid diagnostic tests, and identification of age group-specific, colour-coded artemisinin combination therapy blister packs (p < 0.05). The multivariate logistic regression analysis revealed that odds of Mandla baseline was 0.39, 0.48, 0.34, and 0.07 times lower for malaria-related knowledge on disease etiology, prevention, diagnosis, and treatment, respectively (p < 0.001). Further, participants in districts Balaghat and Dindori showed significantly lower odds for knowledge (p < 0.001) and treatment practices (p < 0.01) compared to Mandla endline. Education, attended training, having a malaria learner's guide, and minimum 10 years' work experience were potential predictors for good treatment practices. CONCLUSION: The findings of the study unequivocally establishes significant improvement in overall malaria-related knowledge and practices of ASHAs in Mandla as a result of periodic training and capacity building efforts. The study suggests that learnings from Mandla district could be helpful in improving level of knowledge and practices among frontline health workers.


Assuntos
Malária , Humanos , Estudos Transversais , Índia , Agentes Comunitários de Saúde , Inquéritos e Questionários
4.
EClinicalMedicine ; 47: 101390, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35480072

RESUMO

Background: Adverse event reporting in oncology trials lacks temporal description. We propose a toxicity summarizing method that incorporates time. Methods: Patients recruited in a phase III trial (NCT01279135) that compared three-dimensional conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) for late toxicity in cervical cancer were included. Adverse events were reported using Common Terminology Criteria for Adverse Events (CTCAE) v3.0 and quality of life (QOL) with EORTC QLQ-C30 and CX24. A total of six symptoms with a related QOL question (diarrhoea, abdominal pain, anorexia, urinary incontinence, frequency and fatigue) were included. Month and severity score [MOSES= ∑ (CTCAE grade x proportionate time)] was calculated. Cumulative-MOSES (C-MOSES) was calculated by summating these 6 individual MOSES. QoL was categorized as "substantially symptomatic" or "not". Receiver operator curve analysis was performed to determine the MOSES cut off that predicts for substantial QOL symptoms. CTCAE and MOSES were tested for accurately categorizing QOL impact. Findings: In the construction dataset, 201/300 patients had symptoms. MOSES > 0.20 had higher accuracy than CTCAE for predicting impact on QOL related to diarrhoea (85% vs. 69%), anorexia (61% vs 51%), abdominal pain (71% vs. 57%), urinary incontinence (72% vs. 61%) and frequency (62% vs. 59%). C-MOSES > 0·70 correlated with reduction in role functioning and global QOL. While no difference was seen in CTCAE grade ≥1 Gastrointestinal (GI) toxicity between 3DCRT or IMRT arm, 3DCRT had higher C-MOSES than IMRT (HR=0.64;95% CI 0.41-0.99, p = 0.04). Interpretation: MOSES has higher accuracy than CTCAE in categorizing symptom specific and functional QOL. These results require further external validation. Funding: None.

5.
Clin Oncol (R Coll Radiol) ; 34(1): e1-e6, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34716084

RESUMO

AIMS: To determine the factors influencing the outcomes of patients with recurrences post-hysterectomy for cervical cancers treated with external beam radiotherapy (EBRT) and interstitial brachytherapy. MATERIALS AND METHODS: This prospective study accrued 90 patients between October 2008 and May 2014. All patients had had a prior hysterectomy and were diagnosed with recurrent vaginal apex cancers with squamous cell carcinomas. All underwent EBRT of 50 Gy (2 Gy/fraction) using tomotherapy-based image-guided intensity-modulated radiotherapy with concurrent chemotherapy of weekly cisplatin (40 mg/m2) followed by high dose rate interstitial brachytherapy boost of 20 Gy (4 Gy/fraction twice a day). Local relapse, disease-free and overall survival were determined. RESULTS: At a median follow-up of 74 months (4-123 months), 10/90 (11%) patients had local failure as the first site of relapse and 12/90 (13.3%) had first distant relapse. Only one patient had synchronous local and distant relapse. The 7-year local relapse-free, disease-free and overall survival were 87.6, 68.3 and 68.3%, respectively. Grade 2 and 3 rectal toxicity were seen in 5.6 and 3.1% of patients, respectively. Among these, two (2.2%) patients underwent temporary diversion colostomy due to vaginal sigmoid and rectovaginal fistula. Grade 2 and 3 bladder toxicity were seen in 5.6 and 1.1% of patients, respectively. In summary, the lateral disease extent (P = 0.048) and the presence of nodal disease at diagnosis (P = 0.08) had a statistically significant or borderline impact on local relapse without any impact on disease-free survival. Tumour size in itself did not affect overall survival. CONCLUSION: With the integration of EBRT and interstitial brachytherapy, most vaginal apex recurrences can be salvaged. An excellent local control and survival is achievable using intensity-modulated radiotherapy with image guidance and concurrent chemotherapy followed by high dose rate interstitial brachytherapy.


Assuntos
Braquiterapia , Carcinoma de Células Escamosas , Neoplasias do Colo do Útero , Feminino , Humanos , Recidiva Local de Neoplasia/radioterapia , Estudos Prospectivos , Dosagem Radioterapêutica , Tomografia Computadorizada por Raios X , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/radioterapia
6.
Clin Oncol (R Coll Radiol) ; 34(3): 189-197, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34736842

RESUMO

AIMS: Uterocervical motions and organ filling during cervical cancer conformal radiotherapy is complex. This prospective, observational study investigated set-up margins (clinical target vo, ume [CTV] to planning target volume [PTV]) for pelvic nodal CTV and internal margin (CTV to internal target volume [ITV]) expansions for uterocervical movements during cervical cancer radiotherapy. MATERIALS AND METHODS: During cervical cancer radiotherapy, a daily kilovoltage, cone-beam computed tomography (CBCT) scan was acquired. Bony anatomy-based rigid co-registration and matching to vessels/pelvic nodal region was carried out to document shifts, errors (systematic and random) and to calculate CTV to PTV margins. Subsequently, soft-tissue matching was carried out at the mid-cervical region and uterine fundus to record shifts, errors and to calculate CTV to ITV margins. RESULTS: In 67 patients, 1380 CBCT scans were analysed. The mean (±standard deviation) couch shifts for CTV pelvic nodal region in all directions were within 4.5-5.3 mm, systematic and random errors 3.0-3.6 mm and set-up margins of within 10 mm (except anterior margin 10.3 mm). For the mid-cervical region, mean shifts were 4.5-5.5 mm, systematic and random errors 2-4 mm amounting to <10 mm internal margins (CTV-ITV for cervix) and for uterine fundus mean (±standard deviation) shifts were larger in the superior direction (12.1 mm) but 4.0-7.5 mm in other directions, systematic and random errors 2-7 mm amounting to anisotropic margins in various directions (10 mm in anterior-posterior and lateral directions, 12-20 mm in superior-inferior directions) (CTV-ITV for uterine fundus). CONCLUSION: Our study suggests anisotropic CTV to ITV and CTV to PTV margins for cervical cancer radiotherapy.


Assuntos
Radioterapia Guiada por Imagem , Neoplasias do Colo do Útero , Colo do Útero/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico , Feminino , Humanos , Movimentos dos Órgãos , Estudos Prospectivos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Erros de Configuração em Radioterapia , Radioterapia Guiada por Imagem/métodos , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/radioterapia
7.
J Stomatol Oral Maxillofac Surg ; 121(3): 248-253, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31336212

RESUMO

INTRODUCTION: Intra-space drug administration have recently gained popularity in the clinical practice posing several advantages over the conventional routes of drug administration. A preliminary prospective randomized triple blind clinical study was conducted to compare the latency and duration of anesthesia with twin mix (1.8ml 2% lignocaine with 1:200,000 epinephrine and 1ml/4mg dexamethasone) and modified twin mix (1.7ml of 4% articaine with 1:100,000 epinephrine and 1ml/4mg dexamethasone) to two conventional local anesthesia solutions along with co-relation of clinical effects in the postoperative phase in patients undergoing extraction of impacted mandibular third molars in terms of patients comfort post-surgery. MATERIALS AND METHODS: The study was conducted among 20 patients with bilateral impacted mandibular third molars who were randomly allotted to two groups, Group A and B. Each patients in both the groups was allotted with study and control site. Among Group A, patients were further divided into Sub-group L (Control) and Sub-group TM (Twin Mix). Group B patients were divided as Sub-group A (Control) and sub-group MTM (Modified Twin Mix). Sub-group L patients received 1.8ml of 2% lignocaine with 1:200,000 adrenaline and sub-group TM received twin mix. Sub-group A received 1.7ml of 4% articaine with 1:100,000 adrenaline and sub-group MTM received modified twin mix solution. All the procedure was performed by a single operator with a gap of 1 month between the two interventions among both the groups. Various subjective and objective parameters were measured pre-operatively and postoperatively to assess the latency and efficacy of various anesthesia solutions used in this study for third molar removal. RESULTS: Mean (±SD) VAS scores for sting on injection and pain were found to be less in TM and MTM sub-group with a score of 2.3 (±0.768) and 2.7 (±0.065) respectively. The anesthetic latency was significantly less in sub-group TM, with a mean (±SD) of 52.4 (±28.3) seconds. Sub-groups A and MTM had longer latency of anesthesia when compared with L and TM sub-groups. The duration of soft tissue anesthesia was maximum in sub-group MTM as compared to the other sub-groups. Patients from control sub-groups among both the groups had increased swelling, post-surgical pain and trismus postoperatively. DISCUSSION: Intra-space administration of twin mix and modified twin mix is clinically efficacious in impacted mandibular third molars surgery with better clinical outcomes postoperatively. We observed one significant difference between TM and MTM that the latter solution provided a prolonged duration of anesthesia increasing the patient's comfort postoperatively after surgical removal of mandibular third molars.


Assuntos
Dente Serotino/cirurgia , Dente Impactado/cirurgia , Método Duplo-Cego , Humanos , Estudos Prospectivos , Extração Dentária
8.
Clin Nucl Med ; 44(9): e517-e518, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31348093

RESUMO

Paratesticular paragangliomas are a rare occurrence. We present the case of a 43-year-old man who presented with paresthesia and paraparesis and was found to have pathologic fracture involving D1 vertebra as a manifestation of metastasis from a nonsecretory right paratesticular paraganglioma.


Assuntos
Paraganglioma/diagnóstico por imagem , Paraganglioma/patologia , Neoplasias Testiculares/diagnóstico por imagem , Neoplasias Testiculares/patologia , Adulto , Humanos , Imageamento por Ressonância Magnética , Masculino , Metástase Neoplásica
9.
Clin Oncol (R Coll Radiol) ; 31(8): 529-538, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31229379

RESUMO

Despite the advances in the primary prevention of cervical cancer, there is an absolute increase in the incidence of cervical cancer as a result of an increase in world population. A vast majority of patients in low and low-middle income countries continue to present at a locally advanced stage, necessitating treatment with chemoradiation and brachytherapy. There is a dearth of equipment and trained professionals for the treatment of cervical cancer, especially in low and low-middle income countries. There is an urgent need to improve treatment availability and develop better treatments. Worldwide trends, however, reveal a low number of therapeutic and innovative research trials in cervical cancer. The present article elucidates the existing challenges and provides solutions to improve outcomes. The proposed strategies hinge on strengthening collaborations for global advocacy.


Assuntos
Carga Global da Doença/métodos , Neoplasias do Colo do Útero/epidemiologia , Feminino , Humanos , Neoplasias do Colo do Útero/patologia
10.
Clin Oncol (R Coll Radiol) ; 31(1): e67-e74, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30322681

RESUMO

AIMS: To report the findings of an audit for radiotherapy errors from a low-middle-income country (LMICs) centre. This would serve as baseline data for radiotherapy error rates, their severity and causes, in such centres where modern error reporting and learning processes still do not exist. MATERIALS AND METHODS: A planned cross-sectional weekly audit of electronic radiotherapy charts at the radiotherapy planning and delivery step for all patients treated with curative intent was conducted. Detailed analysis was carried out to determine the step of origin of error, time and contributing factors. They were graded as per indigenous institutional (TMC) radiotherapy error grading (TREG) system and the contributing factors identified were prioritised using the product of frequency, severity and ease of detection. RESULTS: In total, 1005 consecutive radically treated patients' charts were audited, 67 radiotherapy errors affecting 60 patients, including 42 incidents and 25 near-misses were identified. Transcriptional errors (29%) were the most common type. Most errors occurred at the time of treatment planning (59.7%), with "plan information transfer to the radiation oncology information system" being the most frequently affected sub-step of the radiotherapy process (47.8%). More errors were noted at cobalt units (52/67; 77.6%) than at linear accelerators. Trend analysis showed an increased number of radiotherapy incidents on Fridays and near-misses on Mondays. Trend for increased radiotherapy errors noted in the evening over other shifts. On severity grading, most of the errors (54/60; 90%) were clinically insignificant (grade I/II). Inadequacies and non-adherence towards standard operating procedures, poor documentation and lack of continuing education were the three most prominent causes. CONCLUSION: Preliminary data suggest a vulnerability of LMIC set-up to radiotherapy errors and emphasises the need for the development of longitudinal prospective processes, such as voluntary reporting and a continued education system, to ensure robust and comprehensive safe practises on par with centres in developed countries.


Assuntos
Erros Médicos/tendências , Radioterapia/métodos , Comissão Para Atividades Profissionais e Hospitalares , Estudos Transversais , Humanos , Pobreza , Estudos Prospectivos , Classe Social
11.
Indian J Cancer ; 55(1): 45-49, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30147092

RESUMO

BACKGROUND: Cervical cancer is the second most common cancer among Indian women. This present retrospective study was conducted to report patient outcomes with locally advanced cervical cancer treated in the year 2010. MATERIALS AND METHODS: Case records of cervical cancer patients registered from January 1, 2010, to December 31, 2010 were retrieved. A total of 1200 patients were registered, of which 583 received either definitive or adjuvant radiotherapy (RT). Of these, 345 patients who received complete treatment at our hospital were included for outcome analysis. Descriptive statistics were used to summarize patient- and treatment-related variables, and Kaplan-Meier analysis was performed for survival analysis. RESULTS: The median age was 56 years (range: 33-90). Squamous carcinoma was the most common histology (91.4%) and the majority were FIGO Stage III (45.4%). Median follow-up of the cohort was 44 months (1-85 months). The 5-year disease-free survival (DFS) across stages was 50%. Most important predictor of DFS was FIGO staging (Stage II vs. Stage III: 62% vs. 45%) and use of concurrent chemoradiotherapy (CTRT) l (RT vs. CTRT: 32% vs. 57%, respectively). Patients aged >70 years had a significantly poor DFS at 5 years; however, did not have any effect on survival. Grade 3 or more late toxicity was seen in only 5% of the patients. CONCLUSION: Five-year DFS of 62% and 45% of Stage II and III patients treated under routine care represents comparable stage-matched results to the rest of the world, respectively.


Assuntos
Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/radioterapia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/efeitos adversos , Quimiorradioterapia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia
12.
Cancer Radiother ; 22(4): 334-340, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29859762

RESUMO

PURPOSE: To report our experience of failure mode and effective analysis for high dose rate brachytherapy of gynaecological cancer carried out in our hospital. MATERIALS AND METHODS: Failure mode and effective analysis process described in AAPM TG 100 was followed: a multidisciplinary team consisting of two physicians, physicists, dosimetrists, a medical resident, a nurse, and a secretary was formed. A weekly meeting was held for four months. A process tree was created based on the overview of the entire process, with the main branches as follows: procedure in the operating room, patient imaging, contouring, treatment planning, machine quality assurance and treatment delivery. Each team member assigned the risk probability numbers based on the predefined scoring system. For a particular failure mode, if the risk probability number assigned by one member differed from the other, the highest risk probability number was taken into consideration. RESULTS: The process tree consisted of 185 nodes, with risk probability numbers ranging from 1-220, with 77 possible failure modes. Four nodes were found with risk probability numbers greater than 200, which were considered for immediate process improvements. Twenty-four nodes were found to be with risk probability numbers ranging from 100 to 200. All 24 processes were considered for process improvement, out of which 12 were found effective and feasible, which includes failure nodes with high severity score at least 8. The processes with high-risk probability numbers (greater than 200) were reduced after the introduction of process improvements. For the other processes, standard procedures were modified. The common causes of failure, were found to be due to lack of attention, human error and work pressure. CONCLUSIONS: Failure mode and effective analysis is a useful tool that uses a systematic approach for quality management of a specific process.


Assuntos
Braquiterapia/métodos , Análise do Modo e do Efeito de Falhas na Assistência à Saúde , Neoplasias do Colo do Útero/radioterapia , Feminino , Hospitais , Humanos , Índia , Dosagem Radioterapêutica/normas
13.
J Viral Hepat ; 24(9): 742-749, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28267900

RESUMO

Treatment for chronic hepatitis C virus (HCV) infection has rapidly evolved into interferon-free directly acting antiviral regimens (DAA) that result in high sustained virologic response. DAAs primarily work by suppressing HCV replication and rely less on the immune system than interferon-based therapies. However, it is unclear whether the immune system recovers with suppression of HCV replication and contributes to HCV clearance with DAA therapy. We previously demonstrated HCV clearance is associated with increased HCV-specific immunity in CHCV-GT-1-infected patients during treatment with sofosbuvir (SOF)+ribavirin (RBV). Here, we aimed to analyse changes in HCV-specific immunological responses associated with viral clearance with combination DAA therapy of SOF+ledipasvir (LDV) for 12 weeks in CHCV-GT1 (N=14) patients who relapsed without augmentation of HCV-specific immunity during treatment with SOF+RBV. Phenotypic and functional changes within the T-cell compartment of PBMCs pre- and post-treatment were analysed. Retreatment of relapsers with LDV/SOF resulted in all patients attaining SVR12 . Suppression of HCV was associated with a decline in T-cell exhaustion markers (CD57; Tim3; PD1) along with augmented of HCV-specific T-cell IFN-gamma responses post-treatment. Addition of LDV to SOF was associated with augmentation of HCV-specific immunity and SVR in patients who previously failed SOF+RBV therapy without increased immunity. These findings demonstrate a novel effect of DAA in inducing host immune responses to aid HCV clearance and achieve SVR.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/imunologia , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/imunologia , Imunidade Celular , Resposta Viral Sustentada , Idoso , Feminino , Humanos , Interferon gama/metabolismo , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia , Resultado do Tratamento
14.
J Clin Exp Hepatol ; 7(1): 1-8, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28348464

RESUMO

BACKGROUND: While highly active anti-retroviral therapy (HAART) has improved survival of HIV-infected patients, there is increasing liver disease and progressive Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) related liver disease. AIMS: To study the liver function tests (LFT) and HBV and HCV co-infection in HIV-infected patients. MATERIAL AND METHODS: All HIV-positive patients presenting to a tertiary level hospital from April 2009 to April 2011 were evaluated. Baseline LFT, CD4/CD8 counts, ultrasound abdomen, HBsAg, IgG anti-HBc, HBVDNA, Anti-HCV and HCVRNA were done in all patients. LFT was repeated monthly or more frequently with anti-tubercular therapy (ATT)/HAART. RESULTS: Abnormal LFT were seen in 143/320 (44.6%) HIV-infected patients (n = 320; M-282, F-38; mean age-35.4 ± 7.3 years). Baseline LFT was abnormal in 48 (15%) [hepatotropic viruses-19, alcohol-24, NAFLD-1, disseminated TB-1, idiopathic-03). Subsequent LFT derangement developed in 95/272 (34.9%). In the majority, the LFT abnormality was mild (119/143-83.2%) and multi-factorial [HAART 132 (76.4%), alcohol 69 (48.2%), ATT 31 (21.7%), HBV 16 (11.2%), HCV 15 (10.4%)]. Using multivariate analysis, abnormal LFT were associated with HAART (OR, 5.92; 95%CI, 2.83-12.37), ATT (OR, 2.06; 95%CI, 1.06-3.99) or HCV infection (OR, 2.54; 95%CI, 1.03-6.26). Significant hepatotoxicity requiring drug modification was seen in only 7 cases. HBV, HCV and HBV + HCV co-infection were seen in 37 (11.6%), 28 (8.8%) and 2 (0.6%) respectively. Occult co-infections were rare [HBV-1 (0.3%); HCV-3 (0.9%)]. CONCLUSION: While LFT abnormalities in HIV are common, they are usually mild and multifactorial. HBV and HCV co-infections were seen in 11.6% and 8.8%, respectively. Occult HBV and HCV infections were rare.

15.
Indian J Cancer ; 53(1): 181-5, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27146774

RESUMO

INTRODUCTION: Endometrial cancer (EC) is one of the most common gynecological cancers and the fourth most common cancer in the female. Although clinical evaluation with diagnostic imaging has not yet proved to be accurate enough in the evaluation of tumor extent to replace surgical staging, it may enable optimization of the surgical procedure and a better tailored therapeutic strategy. This study will review the characteristic magnetic resonance imaging (MRI) findings in endometrial carcinomas in the pre-operative staging of endometrial carcinomas and compare it with the newly revised Federation of Gynecology and Obstetrics (FIGO) staging scheme of 2009 based on post-operative surgical histopathology. MATERIALS AND METHODS: It is a retrospective analysis of 36 patients diagnosed and treated for endometrial carcinoma in our institute from January 2009 to December 2012. RESULTS: Majority of the patients (61%) were between the age group of 41-60 years. Most of the patients (72%) were postmenopausal at the time of presentation. Most common histopathology of endometrial carcinoma was endometroid adenocarcinoma (27 patients, 75%). FIGO staging of 12 patients (85.7%) showed concordance with MRI Staging for Stage Ia, with up-gradation of two patients to Stage Ib. CONCLUSION: The information provided by MRI can define prognosis, help planning the surgical approach and identify those patients requiring neoadjuvant chemotherapy or radiation therapy.


Assuntos
Neoplasias do Endométrio/diagnóstico por imagem , Adulto , Animais , Embrião de Galinha , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos
16.
Eur J Radiol Open ; 3: 22-30, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27069975

RESUMO

OBJECTIVES: To assess the diagnostic value of multiparametric-MRI (MPMRI) with hypoxia imaging as a functional marker for characterizing and detecting vaginal vault/local recurrence following primary surgery for cervical cancer. METHODS: With institutional review board approval and written informed consent 30 women (median age: 45 years) from October 2009 to March 2010 with previous operated carcinoma cervix and suspected clinical vaginal vault/local recurrence were examined with 3.0T-MRI. MRI imaging included conventional and MPMRI sequences [dynamic contrast enhanced (DCE), diffusion weighted (DW), 1H-MR spectroscopy (1HMRS), blood oxygen level dependent hypoxia imaging (BOLD)]. Two radiologists, blinded to pathologic findings, independently assessed the pretherapy MRI findings and then correlated it with histopathology findings. Sensitivity, specificity, positive predictive value, negative predictive value and their confidence intervals were calculated. The pre and post therapy conventional and MPMRI parameters were analyzed and correlated with response to therapy. RESULTS: Of the 30 patients, there were 24 recurrent tumors and 6 benign lesions. The accuracy of diagnosing recurrent vault lesions was highest at combined MPMRI and conventional MRI (100%) than at conventional-MRI (70%) or MPMRI (96.7%) alone. Significant correlation was seen between percentage tumor regression and pre-treatment parameters such as negative enhancement integral (NEI) (p = 0.02), the maximum slope (p = 0.04), mADC value (p = 0.001) and amount of hypoxic fraction on the pretherapy MRI (p = 0.01). CONCLUSION: Conventional-MR with MPMRI significantly increases the diagnostic accuracy for suspected vaginal vault/local recurrence. Post therapy serial MPMRI with hypoxia imaging follow-up objectively documents the response. MPMRI and BOLD hypoxia imaging provide information regarding tumor biology at the molecular, subcellular, cellular and tissue levels and this information may be used as an appropriate and reliable biologic target for radiation dose painting to optimize therapy in future.

17.
Ann Surg Oncol ; 23(9): 3009-15, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27075323

RESUMO

PURPOSE: Locally advanced (T3/T4) gallbladder cancers with large fixed portal nodes have a dismal prognosis. If undertaken, surgery entails extensive resections with high morbidity; therefore, in many centers, patients are offered palliative chemotherapy. In this prospective study, we used neoadjuvant concurrent chemoradiation with the intention of downstaging and facilitating R0 resection of these tumors. PATIENTS AND METHODS: Twenty-eight patients with locally advanced carcinoma gallbladder (stage III, having deep liver infiltrations and/or large portal nodes) underwent prior positron emission tomography/computed tomography to rule out metastatic disease. All were treated with concomitant chemoradiation using helical tomotherapy (dose of 57 Gy over 25 fractions to the gross tumor and 45 Gy over 25 fractions to the surrounding nodes) with injectable gemcitabine (300 mg/m(2)/week × 5 weeks). RESULTS: Of the 28 patients, 25 (89 %) successfully completed planned chemoradiation and 20 (71 %) achieved partial or complete radiologic response. Eighteen (64 %) patients were surgically explored, of whom 14 (56 %) achieved R0 resection. At the median follow-up of 37 months for the surviving patients, the median overall survival (OS) was 20 months for all patients. Only one patient recurred in the common bile duct postsurgery, whereas six patients had distant metastasis. The 5-year OS was 24 % for all patients and 47 % for patients with R0 resection. Biliary leak was seen in 6 (43 %) patients, of whom two required interventions. CONCLUSION: Locally advanced unresectable cancers may benefit from neoadjuvant chemoradiation to facilitate a curative resection with a good survival.


Assuntos
Adenocarcinoma/terapia , Quimiorradioterapia , Neoplasias da Vesícula Biliar/terapia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Feminino , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Invasividade Neoplásica , Estadiamento de Neoplasias , Complicações Pós-Operatórias , Estudos Prospectivos , Taxa de Sobrevida , Resultado do Tratamento
18.
Rev Recent Clin Trials ; 10(4): 289-97, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26411952

RESUMO

CONTEXT: Vaginal cancer is a rare gynecologic cancer with very little documentation. OBJECTIVE: Literature search to have useful information for the management of vaginal cancer and share. MATERIAL METHODS: We have searched the PUBMED database, Google search engine and other database. A total of 26 references were taken into account. COMMENTS: Once spread from primary other cancers or vulva is ruled out, vaginal cancer is designated to be primary in origin. It was revealed that majority of vaginal cancers reported are squamous cell carcinomas. The most common risk factors implicated are Human Papiloma Virus, age. Most common presenting symptoms were abnormal vaginal bleeding,. Diagnosis requires pathological confirmation. Management depends on staging work-up. Vaginal cancer is staged by FIGO system of staging and TNM staging. There are many prognostic factors influencing the choice of treatment. Lymph node metastasis is one of the important prognostic factors, others to mention are histology, size, age. In a recent SEER analysis of over 2000 patients, the 5 year disease specific survival was 84% for stage 1, 75% for stage II and 57% for advanced tumors. Early carcinomas are generally treated with either surgery or radiation therapy. Advanced cancers are treated with radiation therapy with simultaneous administration of combined chemotherapy. Preventive strategies include safe sex and HPV vaccination. CONCLUSION: Primary vaginal cancer is a rare entity, if there is no history of cancer cervix or vulva in past or absence of cervical squamous cell carcinoma or vulvar carcinoma within 5 years is usually considered as primary vaginal cancer. Though early stage vaginal cancers have better outcome treated with surgery or radiotherapy or surgery followed by radiotherapy, radiotherapy alone is preferred mode of treatment in vaginal cancers.


Assuntos
Carcinoma de Células Escamosas/patologia , Infecções por Papillomavirus/patologia , Neoplasias Vaginais/patologia , Neoplasias Vaginais/virologia , Adulto , Biópsia por Agulha , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Incidência , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Prognóstico , Doenças Raras , Medição de Risco , Programa de SEER , Resultado do Tratamento , Neoplasias Vaginais/epidemiologia , Neoplasias Vaginais/terapia
20.
Epidemiol Infect ; 143(8): 1599-605, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25314901

RESUMO

Dengue fever, a mosquito-borne viral disease, has become a major public health problem with marked expansion in recent decades. Dengue has now become hyperendemic in India with co-circulation of all the four serotypes. Herein, we report an unprecedented outbreak which occurred during August to October 2011 in Odisha, eastern India. This is the first report of a large epidemic in Odisha. Detailed serological and molecular investigation was carried out to identify the aetiology. Almost half of the samples were found to be dengue antigen (NS1) positive. Further molecular assays revealed circulation of mixed dengue serotypes (DENV-2 and DENV-3). Cosmopolitan genotype of DENV-2 and -3 were identified as the aetiology by phylogenetic analysis. Interestingly, a new lineage of DENV-3 within cosmopolitan genotype was incriminated in this outbreak. The emergence of the unprecedented magnitude of the dengue outbreak with the involvement of a novel lineage of DENV in a newer state of India is a major cause for concern. There is an urgent need to monitor phylodynamics of dengue viruses in other endemic areas.


Assuntos
Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Vírus da Dengue/imunologia , Epidemias , RNA Viral/genética , Dengue Grave/epidemiologia , Adolescente , Adulto , Dengue/epidemiologia , Dengue/virologia , Vírus da Dengue/genética , Feminino , Genótipo , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Filogenia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sorogrupo , Dengue Grave/virologia , Adulto Jovem
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