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1.
Cancer Invest ; 41(9): 789-802, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37909664

RESUMEN

We assessed the efficacy, tolerability, and cost-effectiveness of a novel neoadjuvant regimen comprising docetaxel-cyclophosphamide alternating with epirubicin-cisplatin (ddDCEP) administered biweekly for 16 weeks in 116 patients with early triple-negative breast cancer. This regimen achieved a high pathological complete response (ypT0/TisN0) rate of 55.2% and favorable survival outcomes (30-month event-free survival, 91.2%; overall survival, 97%). Febrile neutropenia was observed in 4.3% of patients, and 98% completed at least six of eight cycles. ddDCEP was more cost-effective than contemporary carboplatin-based regimens. This novel approach offers an economically viable and effective alternative to current chemoimmunotherapy regimens, and merits further investigation.


Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Docetaxel/uso terapéutico , Epirrubicina/uso terapéutico , Cisplatino/efectos adversos , Platino (Metal)/uso terapéutico , Neoplasias de la Mama Triple Negativas/patología , Taxoides/efectos adversos , Resultado del Tratamiento , Ciclofosfamida/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Terapia Neoadyuvante
2.
Ann Hematol ; 101(9): 1987-2000, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35840818

RESUMEN

The role of next-generation sequencing (NGS) in identifying mutations in the driver, epigenetic regulator, RNA splicing, and signaling pathway genes in myeloproliferative neoplasms (MPNs) has contributed substantially to our understanding of the disease pathogenesis as well as disease evolution. NGS aids in determining the clonal nature of the disease in a subset of these disorders where mutations in the driver genes are not detected. There is a paucity of real-world data on the utility of this test in the characterization of triple-negative myeloproliferative neoplasms (TN-MPN). In this study, 46 samples of TN-MPN (essential thrombocythemia (ET) = 17; primary myelofibrosis (PMF) = 23; & myeloproliferative neoplasm unclassified (MPN-u) = 6) were screened for markers of clonality using targeted NGS. Among these, 25 (54.3%) patients had mutations that would help determine the clonal nature of the disease. Eight of the 17 TN-ET (47%) and 13 of the 23 TN-PMF (56.5%) patients had noncanonical mutations in the driver genes and mutations in the genes involved in epigenetic regulation. Identification of mutations categorized as high molecular markers (HMR) in 2 patients helped classify them as PMF with high risk according to the MIPSS 70 scoring system. A novel mutation in the MPIG6B (C6orf25) gene associated with childhood myelofibrosis was detected in a 14-year-old girl. The presence of clonal hematopoiesis could be confirmed in four of the six MPN-u patients in this cohort. This study demonstrates the utility of NGS in improving the characterization of TN-MPN by establishing clonality and detecting noncanonical mutations in driver genes, thereby aiding in clinical decision-making.


Asunto(s)
Trastornos Mieloproliferativos , Neoplasias , Trombocitemia Esencial , Adolescente , Niño , Epigénesis Genética , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Janus Quinasa 2/genética , Mutación , Trastornos Mieloproliferativos/diagnóstico , Trastornos Mieloproliferativos/genética , Trombocitemia Esencial/diagnóstico , Trombocitemia Esencial/genética
3.
Horm Metab Res ; 53(4): 245-256, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33853118

RESUMEN

Multiple Endocrine Neoplasia type-1 (MEN1) is an autosomal dominant disorder with a combined occurrence of tumours of parathyroid glands, pancreatic islets, and anterior pituitary. About 90% of these patients carry mutations in the MEN1 gene, though the spectrum is not well defined in India. Forty clinically suspected cases of MEN1 were enrolled prospectively over six years; 32 patients (23 index-cases and nine affected relatives) with≥2 classical endocrine tumours of MEN1 were considered definite, and eight were categorised as 'MEN1-like'. Details of their clinical presentation, treatment and mutational analysis including MEN1 gene, 3' and 5' untranslated regions (UTR) of MEN1, CDKN1B, and CaSR genes were collated. Asymptomatic first-degree relatives were also screened. Among the 32 definite MEN1 patients, all had primary hyperparathyroidism, 22 (68.7%) had gastroentero-pancreatic neuroendocrine tumours, and 21 (66%) had pituitary adenoma. Of the 23 definite index-cases, 13 (56.5%) carried mutations in the MEN1 gene. Five of nine affected first-degree relatives (55.5%), and four of 10 asymptomatic relatives (40%) also had MEN1 mutations. Seven of 10 MEN1 mutation-negative definite index-cases harboured p.V109G polymorphism in the CDKN1B gene. All eight MEN1-like cases were negative for mutations and large deletions in MEN1, mutations in 3' and 5' UTR of MEN1, CaSR and CDKN1B genes. The study has helped to clearly document the pattern of mutations among Indian MEN1 patients. However, the absence of MEN1 mutation in ~44% of cases and the presence of p.V109G polymorphism in CDKN1B gene raise the question whether such polymorphisms could independently contribute to pathogenesis.


Asunto(s)
Neoplasia Endocrina Múltiple Tipo 1/genética , Mutación , Proteínas Proto-Oncogénicas/genética , Adolescente , Adulto , Anciano , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , Análisis Mutacional de ADN , Femenino , Humanos , India , Masculino , Persona de Mediana Edad , Neoplasia Endocrina Múltiple Tipo 1/metabolismo , Linaje , Estudios Prospectivos , Proteínas Proto-Oncogénicas/metabolismo , Receptores Sensibles al Calcio/genética , Regiones no Traducidas , Adulto Joven
4.
Endocr Pract ; 26(12): 1442-1450, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33471736

RESUMEN

OBJECTIVE: This prospective study was carried out to assess trabecular bone score, bone mineral density (BMD), and bone biochemistry in Indian subjects with symptomatic primary hyperparathyroidism (PHPT), and to study the influence of baseline parathyroid hormone (PTH) on recovery of these parameters following curative surgery. METHODS: This was a 2-year prospective study conducted at a tertiary care centre in southern India. Baseline assessment included demographic details, mode of presentation, bone mineral biochemistry, BMD, trabecular bone score (TBS), and bone turnover markers (BTMs). These parameters were reassessed at the end of the first and second years following curative parathyroid surgery. RESULTS: Fifty-one subjects (32 men and 19 women) with PHPT who had undergone curative parathyroidectomy were included in this study. The mean (SD) age was 44.6 (13.7) years. The TBS, BTMs, and BMD at lumbar spine and forearm were significantly worse at baseline in subjects with higher baseline PTH (≥250 pg/mL) when compared to the group with lower baseline PTH (<250 pg/mL). At the end of 2 years, the difference between high versus low PTH groups (mean ± SD) persisted only for forearm BMD (0.638±0.093 versus 0.698±0.041 g/cm2; P =.01). However, on follow-up visits in the first and second year after curative parathyroidectomy, there was no significant difference in BTMs, BMD at the femoral neck, lumbar spine, and TBS between the 2 groups stratified by baseline PTH. CONCLUSION: The BMD at the forearm remained significantly worse in individuals with high baseline PTH even at 2 years after surgery, while other parameters including TBS improved significantly from baseline. ABBREVIATIONS: 25(OH)D = 25-hydroxyvitamin D; BMD = bone mineral density; BMI = body mass index; BTMs = Bone turnover markers; CTX = C-terminal telopeptide of type 1 collagen; DXA = dual energy X-ray absorptiometry; P1NP = N-terminal propeptide of type 1 procollagen; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; TBS = trabecular bone score.


Asunto(s)
Densidad Ósea , Hiperparatiroidismo Primario , Absorciometría de Fotón , Adulto , Remodelación Ósea , Hueso Esponjoso , Femenino , Humanos , Hiperparatiroidismo Primario/cirugía , India , Masculino , Hormona Paratiroidea , Paratiroidectomía , Estudios Prospectivos
5.
Indian J Med Res ; 147(5): 464-470, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-30082570

RESUMEN

Background & objectives: Peripheral T cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin's lymphomas (NHLs), with universally poor outcome. This study was undertaken to provide data on demographics and outcomes of patients with PTCL who underwent treatment in a single tertiary care centre in southern India. Methods: Retrospective study was done on all patients (age ≥18 yr) diagnosed with PTCL from January 2007 to December 2012. The diagnosis of PTCL was made according to the WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues. Results: A total of 244 adult patients were diagnosed with PTCL (non-cutaneous). The most common subtype was PTCL-not otherwise specified (35.7%), followed by anaplastic large cell lymphoma (ALCL), ALK negative (21.3%), natural killer/T cell lymphoma, angioimmunoblastic T-cell lymphoma (AITL), ALCL, ALK positive, hepatosplenic T cell lymphoma (HSTCL) and adult T cell leukaemia/lymphoma followed in frequency with 13.1, 11.5, 8.6, 8.2 and 1.6 per cent cases, respectively. The three-year Kaplan-Meier overall survival (OS) and event-free survival (EFS) for the patients who received chemotherapy (n=122) were 33.8±5.0 and 29.3±4.7 per cent, respectively. Various prognostic indices developed for T cell lymphomas were found to be useful. Interpretation & conclusions: Except for ALCL, ALK positive, all other PTCLs showed poor long-term outcome with CHOP-based chemotherapy. Novel therapies are needed to improve the outcome.


Asunto(s)
Linfoma de Células T Periférico , Adulto , Humanos , India , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/terapia , Recurrencia Local de Neoplasia , Pronóstico , Estudios Retrospectivos , Centros de Atención Terciaria
6.
Gene ; 895: 147980, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-37951371

RESUMEN

Triple-negative breast cancer (TNBC) is a heterogeneous disease with poor survival compared to other subtypes. Patients with residual disease after neoadjuvant chemotherapy (NAC) face an increased risk of relapse and death. We aimed to characterize the mutational landscape of this subset to offer insights into relapse pathogenesis and potential therapeutic targets. We retrospectively analyzed archived paired (pre- and post-NAC) tumor samples from 25 patients with TNBC with residual disease using a targeted 72-gene next-generation sequencing panel. Our findings revealed a stable mutational burden in both pre- and post-NAC samples, with a median count of 12 variants (IQR 7-17.25) per sample. TP53, PMS2, PTEN, ERBB2, and NOTCH1 variants were observed in pre-NAC samples predominantly. Notably, post-NAC samples exhibited a significant increase in AR gene mutations, suggesting potential prognostic and predictive implications. No difference in mutational burden was found between patients who did and did not receive platinum (p = 0.94), or between those with and without recurrence (p = 0.49). We employed K-means clustering to categorize the patients based on their variant profiles, aiding in the prediction of possible patterns associated with recurrence. Our study was limited by its small sample size and retrospective design, suggesting the need for further validation in larger prospective cohorts.


Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Estudios Retrospectivos , Terapia Neoadyuvante , Estudios Prospectivos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Neoplasia Residual/genética , Neoplasia Residual/tratamiento farmacológico , Neoplasia Residual/patología , Mutación , Recurrencia
7.
Indian J Urol ; 29(4): 282-7, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24235788

RESUMEN

AIMS: There are few studies on the pathology of warty carcinoma (WC) of the penis and these have been from South America. Penile cancers are not uncommon in India. We reviewed the frequency of subtypes of penile squamous carcinoma (SC) and the pathological features and outcome of WC when compared to squamous carcinoma-not otherwise specified (SC-NOS). We also compared the clinicopathological features of WC in our series with those published earlier. MATERIALS AND METHODS: We studied 103 cases of penile cancers over 6 years. Cases were classified into different subtypes according to established histologic criteria. Clinicopathologic features were studied in detail and compared among the different subtypes, especially between WC and SC-NOS. The patients were followed-up and disease free survival in months was noted. RESULTS: SC-NOS constituted 75.7% of all penile cancer cases in our series. The frequency of other subtypes was WC: 9.7%, verrucous: 3.9%, basaloid type and papillary type: 0.97% each, and mixed types 8.7%. The average tumor size and depth of invasion did not differ significantly between the two subtypes. Frequency of lymphovascular emboli and percentage of lymph node metastasis in WC (30 and 10%) were lesser than in SC-NOS (49.37 and 26.58%), respectively. There were no recurrences after partial penectomy in the WC subtype. In the SC-NOS type, three cases had recurrence after partial/total penectomy. CONCLUSION: Warty carcinoma constitutes nearly 10% of all penile squamous cell cancers. These patients seem to have a less aggressive behavior than SC-NOS.

8.
Indian J Pathol Microbiol ; 66(4): 714-719, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38084521

RESUMEN

Classifying diffuse large B cell lymphomas, not otherwise specified (DLBCL, NOS), is based on their cell-of-origin (COO) which is included in the WHO classification (2016), is essential to characterize them better in context of prognostication. While gene expression profiling (GEP) considered the gold standard and more recently, the Nanostring-based approach, classify these tumors accurately, many laboratories with limited resources and instrumentation need an alternate approach that is reliable, inexpensive, and with a reasonable turnaround. The Reverse Transcriptase Multiplex Ligation Dependant Probe Amplification (RT-MLPA) to subtype DLBCL, NOS cases, as designed by CALYM group appears to provide a good alternative but needs to be validated in other centres. Therefore, this study evaluated DLBCL, NOS and compared the results of RT-MLPA to that obtained by immunohistochemistry using the Hans algorithm. Materials and Methods: Sixty-five DLBCL, NOS cases were included and the RT-MLPA was set up and standardized using probes that were designed by the CALYM study group. Briefly, RNA was extracted converted to cDNA and the 21-gene expression classifier that also included probes to detect MYD88 mutations and EBER mRNA was performed by MLPA. The results were analyzed by the open home grown software designed by the same group and compared to the results obtained by IHC. Results: Forty-four of the sixty-five cases provided concordant results (k = 0.35) and if the MYD88 results were to be used as a classifier the concordance would have improved from 67.7% to 82%. The 21 discordant cases were divided into five categories to provide a possible explanation for the discordance. Further 26% and 31% of the samples tested were positive for MYD88 mutations and EBER mRNA, respectively. The test had a turnaround of three days. Conclusion: The test provided moderate (67.7%) concordance when compared with IHC and perhaps would have provided higher concordance if compared with GEP. The test also has the advantage of providing information on the MYD88 and EBV infection status. It was found to be reliable, easy to perform and standardize, requiring only routine instruments available in most molecular laboratories. The RT-MLPA assay therefore provides an alternative for laboratories that would require subtyping of DLBCL, NOS cases in the absence of an access to GEP or other instrument intensive methods.


Asunto(s)
Linfoma de Células B Grandes Difuso , ADN Polimerasa Dirigida por ARN , Humanos , ADN Polimerasa Dirigida por ARN/genética , ADN Polimerasa Dirigida por ARN/metabolismo , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Perfilación de la Expresión Génica , ARN Mensajero , Proteínas Adaptadoras Transductoras de Señales/genética , Pronóstico
9.
Mol Cytogenet ; 16(1): 24, 2023 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-37716945

RESUMEN

BACKGROUND: Cytogenetic analysis continues to have an important role in the management of acute myeloid leukemia (AML) because it is essential for prognostication. It is also necessary to diagnose specific categories of AML and to determine the most effective form of treatment. Reports from South Asia are few because the availability of cytogenetic services is relatively limited. METHODS: We performed a retrospective analysis of the cytogenetic findings in adults with AML seen consecutively in a single centre in India. The results were categorised according to the 2022 World Health Organisation (WHO), International Consensus Classification (ICC) and European LeukemiaNet (ELN) classifications. RESULTS: There were 1791 patients aged 18-85 years (median age 42, 1086 males). Normal karyotypes were seen in 646 (36%) patients. The 1145 (64%) abnormal karyotypes comprised 585 (32.7%) with recurrent genetic abnormalities (RGA), 403 (22.5%) with myelodysplasia-related cytogenetic abnormalities (MRC), and 157 (8.8%) with other abnormalities. There were 567 (31.7%) patients with solitary abnormalities and 299 (16.7%) with two abnormalities. Among the 279 (15.6%) patients with ≥ 3 abnormalities, 200 (11.2%) had complex karyotypes (CK) as per the WHO/ICC and 184 (10.3%), as per the ELN definition. There were 158 (8.8%) monosomal karyotypes (MK). Patients with normal karyotypes had a higher median age (45 years) than those with abnormal karyotypes (40 years, p < 0.001), and those with ≥ 3 abnormalities (43 years), than those with fewer abnormalities (39 years, p = 0.005). Patients with CK (WHO/ICC) and monosomal karyotypes had a median age of 48 years. Those with RGA had a lower median age (35 years, p < 0.001) than MRC (46 years) or other abnormalities (44 years). The t(15;17) was the most common abnormality (16.7%),followed by trisomy 8 (11.6%), monosomy 7/del 7q (9.3%), t(8;21) (7.2%), monosomy 5/del 5q (6.7%) and monosomy 17/del 17p (5.2%). CONCLUSION: Our findings confirm the lower age profile of AML in India and show similarities and differences with respect to the frequencies of individual abnormalities compared to the literature. The frequencies of the t(15;17), trisomy 8 and the high-risk abnormalities monosomy 7 and monosomy 5/del 5q were higher, and that of the inv(16), lower than in most reports.

10.
Turk Patoloji Derg ; 38(1): 25-33, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34514582

RESUMEN

OBJECTIVE: Recent WHO 2017 guidelines mandates mutational analysis for the diagnosis of myeloproliferative disorders (MPN). JAK2V617F has been found in only 50-60% of Primary myelofibrosis (PMF) and Essential thrombocythaemia (ET). A recently discovered somatic Calreticulin (CALR) mutation has been linked to MPN. This mutation leads to a common 36 amino acid C-terminus that can be detected accurately by immunohistochemistry (IHC). Limited published literature exists on the utility of CAL2IHC as a diagnostic tool. The study aimed to validate the sensitivity and specificity of CAL2IHC for its use as a cost effective and rapid diagnostic tool. MATERIAL AND METHOD: Subjects included 23 patients of MPN (15 PMF, 6 ET, 2 PV (Polycythaemia Vera)), diagnosed between January 2014 to November 2016 with adequate available tissue for histopathological and mutational analysis. Mutational analysis had been performed with Bidirectional Sanger sequencing. CAL2IHC was performed in all cases and the sensitivity and specificity of CAL2 IHC to identify the Calreticulin mutation was evaluated with respect to comparison with the gold standard mutation analysis. RESULTS: In the 23 MPN patients, CAL2 IHC detected CALR mutation with a sensitivity of 95% and a specificity of 100%. Both cases of PV were negative for CAL2IHC. CAL2IHC showed cytoplasmic positivity in ET (2-3+) and PMF (1-3+) with (62-69%) positive megakaryocyte staining. All 6 ET cases and all 14/15 PMF cases were CAL2IHC positive, and these results were concordant with CALR mutational analysis. CONCLUSION: Anti-CAL2 immunohistochemistry is a specific and a sensitive marker to detect CALR mutation. Its' cost effectiveness and fast results are quite advantageous as compared to molecular analysis.


Asunto(s)
Calreticulina , Trastornos Mieloproliferativos , Neoplasias , Calreticulina/genética , Calreticulina/metabolismo , Análisis Costo-Beneficio , Humanos , Inmunohistoquímica , Mutación , Trastornos Mieloproliferativos/diagnóstico , Trastornos Mieloproliferativos/genética , Trastornos Mieloproliferativos/metabolismo , Trastornos Mieloproliferativos/patología , Estudios Retrospectivos
11.
Indian J Pathol Microbiol ; 65(1): 137-141, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35074979

RESUMEN

Primary follicular lymphoma of the gut (PFL-GI) is a rare entity. This study aims to compare the clinicopathologic features of PFL-GI with cases of gastrointestinal involvement by disseminated nodal follicular lymphoma. This is a retrospective study with 6 cases of primary follicular lymphoma and 8 cases of secondary involvement of the gut, over a period of 9 years. The slides and blocks were retrieved and reviewed. Clinical data was obtained from hospital records. Clinicopathologic features were compared. PFL-GI cases had a slightly higher median age group (p value 0.23) and no gender predilection when compared to cases with secondary involvement which showed a female preponderance. Para-aortic lymphadenopathy was seen in all secondary cases whereas none of the primary cases showed significant lymphadenopathy. The only microscopic feature that was different was the presence of hollowed out pattern of immunostaining for follicular dendritic cells seen in all cases of PFL-GI but in none of the secondary cases.


Asunto(s)
Tracto Gastrointestinal/patología , Linfoma Folicular/complicaciones , Linfoma Folicular/patología , Adulto , Femenino , Técnicas Histológicas , Humanos , India , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estudios Retrospectivos
12.
Hematol Oncol Stem Cell Ther ; 15(2): 13-20, 2022 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-33789164

RESUMEN

OBJECTIVE/BACKGROUND: Recurrent somatic mutations in the JAK2, calreticulin (CALR), and the MPL genes are described as drivers of BCR-ABL1-negative myeloproliferative neoplasms (MPN) that includes polycythemia vera (PV), essential thrombocytosis (ET), primary myelofibrosis (PMF), and MPN unclassified (MPN-U). METHODS: We describe the mutation profile and clinical features of MPN cases diagnosed at a tertiary care center. JAK2V617F and MPL (S505/W515) mutations were screened by allele-specific polymerase chain reaction, while CALR exon 9 and JAK2 exon 12 mutations were screened by fragment analysis/Sanger sequencing. Among the 1,570 patients tested for these mutations during the study period, 407 were classified as MPN with a diagnosis of PV, ET, PMF, and MPN-U seen in 30%, 17%, 36%, and 17%, respectively, screened. RESULTS: Similar to previous reports from Asian countries, the incidence of PMF was the highest among the classic MPN. JAK2V617F mutation was detected in 90% of PV, 38% of ET, 48% of PMF, and 65% of MPN-U. JAK2 exon 12 mutations were seen in 5.7% of PV and 1.4% of PMF. CALR exon 9 mutations were seen in 33% of ET, 33% of PMF, and 12% of MPN-U. MPL mutations were detected in 2.8%, 2.7%, and 2.9% of ET, PMF, and MPN-U, respectively. Fifteen % of PMF, 26% of ET, and 22% of MPN-U were triple negative. CONCLUSION: There was a significantly higher incidence of CALR mutation in PMF and ET cases. Our study highlights the challenges in the diagnosis of JAK2-negative PV and the need for harmonization of criteria for the same.


Asunto(s)
Trastornos Mieloproliferativos , Policitemia Vera , Trombocitemia Esencial , Humanos , Calreticulina/genética , Calreticulina/metabolismo , India , Janus Quinasa 2/genética , Mutación , Trastornos Mieloproliferativos/genética , Policitemia Vera/genética , Receptores de Trombopoyetina/genética , Receptores de Trombopoyetina/metabolismo , Trombocitemia Esencial/genética
13.
Nephrol Dial Transplant ; 26(10): 3412-5, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21775763

RESUMEN

Current treatment of Kaposi's sarcoma is reduction of immunosuppression with or without addition of mammalian target of rapamycin inhibitors (mTORi). Akt signalling plays a central role in oncogenesis of Kaposi's sarcoma. We describe a case of multifocal Kaposi's sarcoma in a renal allograft recipient, which showed unsatisfactory early response to immunosuppression reduction along with everolimus therapy but completely resolved after adding leflunomide. mTORi impair Kaposi's sarcoma oncogenesis by inhibiting mTOR downstream from the Akt signalling. Leflunomide inhibits Akt phosphorylation. This synergistic effect may be beneficial in treatment of Kaposi sarcoma and needs to be explored in trials.


Asunto(s)
Inmunosupresores/uso terapéutico , Isoxazoles/uso terapéutico , Enfermedades Renales/complicaciones , Trasplante de Riñón/efectos adversos , Sarcoma de Kaposi/tratamiento farmacológico , Sirolimus/análogos & derivados , Antineoplásicos/uso terapéutico , Everolimus , Humanos , Enfermedades Renales/terapia , Leflunamida , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sarcoma de Kaposi/etiología , Sirolimus/uso terapéutico , Trasplante Homólogo , Resultado del Tratamiento
14.
AACE Clin Case Rep ; 7(1): 69-71, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33851024

RESUMEN

OBJECTIVE: Primary hyperparathyroidism (PHPT) has varied clinical presentations. Hematologic abnormalities secondary to PHPT have been described before. However, pancytopenia as the initial presentation has rarely been reported. We report a patient with PHPT who presented for evaluation of pancytopenia. METHODS: Histopathology of the bone marrow at presentation is described. Bone biochemistry results and the hematologic profile before and after curative parathyroidectomy are presented. RESULTS: A 48-year-old woman presented with pancytopenia (hemoglobin, 6.3 g/dL; total leucocyte count, 3000 cells/mm3; and platelet count, 60 000 cells/mm3), and her bone marrow study showed marrow fibrosis. Biochemical evaluation revealed hypercalcemia (15.5 mg/dL), hypophosphatemia (2.2 mg/dL), and elevated total alkaline phosphatase (4132 U/L). Bone mineral density assessment by dual-energy X-ray absorptiometry scan revealed osteoporosis at all 3 sites, which was more severe in the distal one third of the forearm. Further investigations confirmed the diagnosis of PHPT (serum parathyroid hormone, 2082 pg/mL). Following curative parathyroidectomy, in addition to normalization of calcium, there was restoration of all 3 hematologic cell lines at 3 months. CONCLUSION: Pancytopenia may be a rare manifestation of PHPT. Thus, it may be prudent to evaluate the calcium profile in patients with chronic refractory anemia and pancytopenia.

15.
Ecancermedicalscience ; 15: 1207, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33912232

RESUMEN

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is associated with poor prognosis and access to anti-HER2 treatment is still a challenge in lower-middle income countries. The availability of the biosimilar trastuzumab has improved access by lowering the costs. We report the pattern of use of neoadjuvant ± adjuvant trastuzumab and outcomes in patients with HER2-positive non-metastatic breast cancer treated with regimens incorporating shorter durations of therapy and the use of the biosimilar trastuzumab compared to the innovator. METHODS: We conducted a retrospective analysis of patients with non-metastatic HER2-positive breast cancer treated with neoadjuvant ± adjuvant trastuzumab (innovator (n = 34 (33%)) and biosimilar (n = 70 (67%)) manufactured by Biocon Biologics) with chemotherapy. Information regarding chemotherapy regimens, duration of trastuzumab use (≤12 weeks and >12 weeks), pathological response (Miller Payne grade), disease free survival (DFS), overall survival (OS) and safety data were collected from electronic medical records. RESULTS: A total of 135 patients were analysed with a median age of 51 years (range: 23-82); of these, 57% were postmenopausal, 31.8% were hormone receptor positive and 62.9% had stage III disease. The overall pathological complete response (p-CR) in both breast and axilla increased to 37.6% in patients treated with trastuzumab preoperatively as compared to 22.2% in patients who did not receive any trastuzumab. Patients receiving innovator trastuzumab and biosimilar trastuzumab showed a p-CR of 28.5% and 41.7%, respectively. At a median follow-up of 42 months (range: 3-114), there were 18 relapses and 11 deaths. The 3-year DFS was 87.1% and OS was 92.2%. Cardiac dysfunction developed in 4 of 78 (5.1%) evaluable patients. CONCLUSION: Access to anti-HER2 therapy in the treatment of non-metastatic HER2-positive breast cancer in resource-constrained settings has improved significantly with the availability of the biosimilar trastuzumab. Imbalances in patient profiles at baseline in routine clinical practice led to inconclusive outcomes of ≤12 weeks versus >12 weeks trastuzumab treatment. However, on the basis of historical data, patients could be offered shorter duration of trastuzumab when a standard 1-year treatment of adjuvant trastuzumab is not feasible in resource-constrained settings. The p-CR using the biosimilar trastuzumab in neoadjuvant treatment has been observed to be comparable to the innovator trastuzumab.

16.
Lung India ; 37(3): 232-237, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32367845

RESUMEN

CONTEXT: Tuberculosis (TB) and diabetes mellitus (DM) are converging epidemics, each worsening the morbidity of the other. A study of the prevalence of DM in TB patients assumes great importance. AIMS: The study aims to evaluate the association between DM and TB over a 10-year period in a tertiary care hospital. SETTINGS AND DESIGN: A retrospective observational study in a southern Indian tertiary care teaching hospital was conducted. MATERIALS AND METHODS: All patients with TB diagnosed and treated during the 10-year study period were identified from the hospital database. All relevant clinical, microbiological, and laboratory results pertaining to diagnosis of DM were collected. The diagnosis of TB and DM was made as per the standard criteria. STATISTICAL ANALYSIS: Categorical variables were analyzed using Chi-square test while continuous variables using independent sample t-test. RESULTS: From 2001 to 2012, we studied 1979 TB patients among whom data on DM were available. The prevalence of DM was 29%, 21%, and 14%, in smear positive, smear negative and extrapulmonary TB respectively (overall 24%). Diabetics were more likely to be men (77.3% vs. 61%;P = 0.001); >40 years of age (81.7% vs. 38.9%;P < 0.001); heavier (59.96 vs. 50.37;P = 0.004); tobacco smokers (16.1% vs. 8.1%;P < 0.001); and alcohol consumers (6.8% vs. 4%;P = 0.02). They were less likely to be HIV coinfected (1.8% vs. 6.1%;P < 0.001). HIV coinfection was seen in 5% of patients and was substantially higher in extrapulmonary TB group (19.4%). Multidrug-resistant TB was lower in DM (11.7%) compared to non-DM (15.9%) (P = 0.02). Overall, 48% of the DM patients were diagnosed at the time of TB diagnosis. Over 10 years, no obvious changes in the trend were evident. CONCLUSIONS: Over a 10-year study period, 24% of the TB patients were diabetic, nearly half were detected at the time of TB diagnosis. There may be a good case for screening all TB patients for DM.

17.
Acta Cytol ; 63(3): 182-188, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30889578

RESUMEN

BACKGROUND: Atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) criterion in thyroid fine-needle aspirates (FNAs) has been a heterogeneous entity with much inter-observer variation. Sub-categorisation of AUS/FLUS has been observed to play an effective role in risk stratification. We aimed to validate AUS/FLUS sub-categorisation in correlation with the spectrum of malignancy. STUDY DESIGN: Subjects included patients with AUS/FLUS diagnosed between January 2015 and December 2016. AUS/FLUS cases were sub-categorised into those exhibiting (1) architectural atypia, (2) cytological atypia, (3) architectural and cytological atypia, (4) AUS with Hürthle cells, and (5) AUS not otherwise specified (AUS-NOS). Each sub-category was correlated with their corresponding incidence of malignancy in surgical resections. RESULT: The overall incidence of AUS/FLUS in our centre was 13% (132/1,018). On retrospective review of 117 patients with AUS/FLUS, smears with cytological atypia showed a higher incidence of malignancy (78.3%) than those with architectural atypia (75.3%). AUS/FLUS cases with both cytological and architectural atypia had a malignancy rate of 71.4%. CONCLUSION: AUS/FLUS cases with cytological atypia had a higher risk of malignancy than those with architectural atypia. The sub-categorisation of AUS/FLUS is diagnostically important for the proper risk stratification of patients.


Asunto(s)
Adenocarcinoma Folicular/patología , Biopsia con Aguja Fina/métodos , Glándula Tiroides/patología , Neoplasias de la Tiroides/patología , Nódulo Tiroideo/patología , Biopsia con Aguja Fina/clasificación , Biopsia con Aguja Fina/estadística & datos numéricos , Femenino , Humanos , India , Masculino , Variaciones Dependientes del Observador , Células Oxífilas/patología , Patología Clínica/métodos , Patología Clínica/estadística & datos numéricos , Reproducibilidad de los Resultados , Estudios Retrospectivos
18.
Indian J Pathol Microbiol ; 62(1): 73-78, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30706863

RESUMEN

CONTEXT: Relative risk of non-Hodgkin lymphoma (NHL) in people living with HIV is 60-200 times that of normal population. This is the largest series from India on lymphomas arising in HIV-infected individuals including workup for Epstein-Barr virus (EBV) and human herpesvirus-8 (HHV-8). AIMS: This study aims to ascertain the distribution and detailed clinicopathologic features of lymphoma arising in HIV-infected persons in India. SETTINGS AND DESIGN: The study was done during the period of 2007-2011 in the pathology department of a tertiary care center in South India. SUBJECTS AND METHODS: All cases diagnosed as lymphoma in the department of pathology during the study period were identified, and patients with HIV positive by serology were included in the study. Clinical details were obtained from electronic records, slides were reviewed and tissue blocks retrieved, and immunohistochemistry for HHV-8 and in situ hybridization for EBV-encoded RNA was done. STATISTICAL ANALYSIS USED: Descriptive statistics were done using SPSS software. Kaplan-Meier curves were used to do survival analysis. RESULTS: Of 3346 patients diagnosed with lymphoma, 73 (2%) were diagnosed to be positive for HIV. About 87.6% of the cases were NHL, of which diffuse large B-cell lymphoma was the most common and plasmablastic lymphoma was the second common subtype. Survival was uniformly poor in 36% of the cases where follow-up was available. CONCLUSIONS: The striking differences from world literature included higher frequency of plasmablastic lymphomas, lack of primary central nervous system lymphomas, and low association with HHV8.


Asunto(s)
Infecciones por VIH/complicaciones , Linfoma no Hodgkin/diagnóstico , Linfoma no Hodgkin/patología , Adolescente , Adulto , Anciano , Niño , Registros Electrónicos de Salud , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/epidemiología , Femenino , Infecciones por VIH/epidemiología , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Inmunohistoquímica , Hibridación in Situ , India/epidemiología , Linfoma de Células B Grandes Difuso/complicaciones , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/patología , Linfoma no Hodgkin/epidemiología , Masculino , Persona de Mediana Edad , ARN Viral/genética , Adulto Joven
19.
Int J Gynecol Pathol ; 27(3): 398-401, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18580317

RESUMEN

A case of müllerian adenosarcoma arising in ovarian endometriosis is reported in which the whole of the mesenchymal component exhibited striking deciduoid morphology, a phenomenon that has not been previously described. The patient was not taking hormonal preparations. We discuss the differential diagnosis and the possible pathogenesis of the deciduoid stromal alteration.


Asunto(s)
Adenosarcoma/patología , Endometriosis/patología , Neoplasias Ováricas/patología , Adenosarcoma/etiología , Adulto , Endometriosis/complicaciones , Femenino , Humanos , Neoplasias Ováricas/etiología
20.
J Reprod Med ; 53(11): 874-6, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19097522

RESUMEN

BACKGROUND: Vaginal wall cysts and pelvic organ prolapse, although commonly encountered, rarely occur together. Typically, the differential diagnosis of vaginal wall prolapse includes anterior and/or posterior wall support defects. Although large vaginal cysts have the potential to disturb normal vaginal supports, these coexisting abnormalities are rarely reported. CASE: A 39-year-old multipara woman presented with a progressively enlarging vaginal bulge for 6 years, erroneously diagnosed as an enterocele with a unilateral paravaginal support defect. The enterocele was subsequently confirmed to be a 10 x 5-cm, thick-walled cystic mass histologically confirmed to be a Bartholin gland abscess. CONCLUSION: Unusual forms of vaginal prolapse require adequate ancillary investigation such as imaging to avoid diagnostic error and to improve preoperative planning and treatment.


Asunto(s)
Absceso/diagnóstico , Glándulas Vestibulares Mayores , Quistes/diagnóstico , Errores Diagnósticos , Hernia/diagnóstico , Absceso/patología , Absceso/cirugía , Adulto , Glándulas Vestibulares Mayores/patología , Glándulas Vestibulares Mayores/cirugía , Quistes/patología , Quistes/cirugía , Femenino , Herniorrafia , Humanos
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