Nadia Talat

King's College Hospital NHS Foundation Trust, London, ENG, United Kingdom

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Publications (15)74.71 Total impact

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    ABSTRACT: This study analyses new information on gene mutations in paragangliomas and puts them into a clinical context. A suspicion of malignancy is critical to determine the workup and surgical approach in adrenal (A-PGL) and extra-adrenal (E-PGL) paragangliomas (PGLs). Malignancy rates vary with location, family history, and gene tests results. Currently there is no algorithm incorporating the above information for clinical use. A sum of 1 821 articles were retrieved from PubMed using the search terms "paraganglioma genetics". Thirty-seven articles were selected of which 9 were analyzed. It was found that 599/2 487 (24%) patients affected with paragangliomas had a germline mutation. Of these 30.2% were mutations in SDHB, 25% VHL, 19.4% RET, 18.4% SDHD, 5.0% NF1, and 2.0% SDHC genes. A family history was positive in 18.1-64.3% of patients. Adrenal PGLs accounted for 55.1% in mutation (+) and 81.0% in mutation (-) patients (RR 1.2, p<0.0001). Bilateral A-PGLs accounted for 56.4% in mutation (+) and 3.2% in mutation (-) patients (RR 8.7, p<0.0001). E-PGL were found in 33.6% of mut+ and 17.3% of mut- (RR 1.7, p<0.0001). In mutation (+) patients PGLs malignancy varied with location, adrenal (6.4%) thoraco-abdominal E-PGL (38%), H & N E-PGL (10%). Malignancy rates were 8.2% in mutation (-) and lower in mutation (+) PGLs except for SDHB 36.5% and SDHC 8.3%. Exclusion of a mutation lowered the probability of malignancy significantly in E-PGL (RR 0.03 (95% CI 0.1-0.6); p<0.001). Mutation analysis provides valuable preoperative information to assess the risk of malignancy in A-PG and E-PGLs and should be considered in the work up of all E-PGL lesions.
    07/2014;
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    ABSTRACT: Parathyroid cancer has a poor mid-term prognosis, often because of local recurrence, observed in half of all patients. Modern diagnostic workup increasingly enables a preoperative diagnosis of parathyroid cancer. There is limited evidence that more comprehensive oncologic surgery can reduce the risk of local recurrence. This study aims to identify the best specific surgical approach in parathyroid cancer. This observational cohort study comprises 19 consecutive patients who had undergone oncologic or nononcologic resection for parathyroid cancer. Baseline parameters were compared by using univariate analysis; outcomes were assessed by χ (2) testing and Kaplan-Meier statistics. Fifteen of 19 patients were primarily operated on in our tertiary center between 1996 and 2013, and four were referred for follow-up because of their cancer diagnosis. Patient cohorts defined by histologic R-status were comparable for established risk factors: sex, calcium levels, low-risk/high-risk status, and presence of vascular invasion. Oncologic resections were performed in 13 of 15 patients primarily treated in the center and 0 of 4 treated elsewhere (χ (2) = 5.6; p < 0.01). R0 margins were achieved in 11 of 13 (85 %) undergoing oncologic resection and 1 of 6 (17 %) undergoing local excision (χ (2) = 8.1; p < 0.01). R0 margins and primary oncologic resection were associated with higher disease-free survival rates (χ (2) = 7.9; p = 0.005 and χ (2) = 4.7; p = 0.03, respectively). Revision surgery achieved R0 margins in only 2 of 4 (50 %) of patients. In parathyroid cancer, a more comprehensive surgery (primary oncologic resection) provides significantly better outcomes than local excision as a result of reduction of R1 margins and locoregional recurrence.
    Annals of Surgical Oncology 02/2014; · 4.12 Impact Factor
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    ABSTRACT: Background: Mid-term outcome information in risk stratified patient cohort is needed to inform prognosis in individual patients with paragangliomas (PGL), adjuvant therapy choice and future research. The objective is to define the outcome relevance of a novel risk stratification scheme for PGLs. Design: A classification scheme for PGLs was devised and specimen were assessed for invasion capacity (infiltrative edges with broad fibrous bands, extra-adrenal extension [recording capsular, microscopic periadrenal and gross periadrenal], capsular and peritumoral vascular invasion [recording thin- and thick-walled blood vessels]), tumorigenic expansion (expansile nodules with diffuse areas, hypercellular homogenous areas, necrosis [recording multifocal and confluent subtypes]) and mitogenic activity (MFC/10HPF, presence of atypical mitotic figures). Patients were prospectively stratified as low risk or high risk (presence of at least one feature of invasive capacity and two features of tumorigenic expansion). Patients underwent systematic treatment and follow up for their PGLs in a tertiary referral center. Results: The multilevel analysis based on 78 patients identified statistically significant differences in clinical and biochemical presentation between low risk and high risk patients for gender (p<0.05), noradrenalin (4.6±8.5 vs 11.6±16.9), dopamine (0.6±0.3 vs 1.7±2.4), size of lesion (49.8±19.5 vs 89.2±45.8) and malignancy, 0% vs 21.6% (p<0.01), treatment modalities for MIBG therapy, 0% vs 40.5% (p<.0001), MVR, 0% vs 23.3% (p<.001) and lymph node dissection, 13.5% vs 40.5% (p<0.01) and distant metastases, 0% vs 21.6% (p<0.01). Disease free survival was significantly lower in HR patients 0% vs 78.4% (p=0.004). Histological risk stratification predicts DFS with AUC of 0.8 (95% CI: 0.69-0.90; p<0.01). 7/37 patients with HR had a synchronous diagnosis of malignancy based on other criteria and 4 patients suffered local recurrence. Conclusions: Stratification as low risk excluded a synchronous diagnosis of malignancy and disease recurrence of a follow-up interval of 1-75 months (median 12 months). A high-risk status is associated with high risk of malignancy and disease recurrence.
    Modern Pathology 02/2014; 27(S2):152. · 5.25 Impact Factor
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    ABSTRACT: The aim of this study was to assess the utility of combined C-methionine and F-FDG PET/CT imaging in hyperparathyroidism. We reviewed all scans performed for hyperparathyroidism with both C-methionine and F-FDG PET/CT or PET in our institution since 1993. Forty-three patients (47 pairs of scans) were included (13 men and 30 women) with a mean age of 63 years. C-methionine and F-FDG PET/CT scans were classified as positive or negative for localization of abnormal parathyroid tissue, and the site of uptake was noted in the positive scans. Other concurrent imaging (Tc-MIBI scintigraphy, ultrasonography, CT, or MRI) findings were also noted when performed. Clinical follow-up information was available in 27 patients (30 episodes). Of the 47 PET scan episodes, 23 (49%) were positive. Twenty-two C-methionine scans showed abnormal focal localization of which 10 also showed concordant abnormal F-FDG uptake. One patient was positive with F-FDG and negative with C-methionine.Of the 16 patients who underwent subsequent surgery, 6 had concordant C-methionine, F-FDG, and surgical findings; 6 had concordant C-methionine and surgical findings; 1 had concordant F-FDG and surgical findings; and 3 had both PET scans negative but had adenomas excised during surgery.Of the 3 with both PET scans negative and discordant surgical findings, 1 had mediastinal parathyroid lipoadenoma excised and 2 had normally sited parathyroid adenoma excised. F-FDG PET/CT rarely provides additional information and could be saved for patients in whom C-methionine PET/CT is negative.
    Clinical nuclear medicine 01/2014; · 3.92 Impact Factor
  • Klaus-Martin Schulte, Nadia Talat
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    ABSTRACT: Parathyroid cancer is rare, but often fatal, as preoperative identification of malignancy against the backdrop of benign parathyroid disease is challenging. Advanced genetic, laboratory and imaging techniques can help to identify parathyroid cancer. In patients with clinically suspected parathyroid cancer, malignancy of any individual lesion is established by three criteria: demonstration of metastasis, specific ultrasonographic features, and a ratio >1 for the results of third-generation:second-generation parathyroid hormone assays. Positive findings for all three criteria dictate an oncological surgical approach, as appropriate radical surgery can achieve a cure. Mutation screening pinpoints associated conditions and asymptomatic carriers. Molecular profiling of tumour cells can identify high-risk features, such as differential expression of specific micro-RNAs and proteins, and germ line mutations in CDC73, but is unsuitable for preoperative assessment owing to the potential risks associated with biopsy. A validated, histopathology-based prognostic classification can identify patients in need of close follow-up and adjuvant therapy, and should prove valuable to stratify clinical trial cohorts: low-risk patients rarely die from parathyroid cancer, even on long-term follow-up, whereas 5-year mortality in high-risk patients is around 50%. This insight has improved the approach to parathyroid cancer by enabling risk-adapted surgery and follow-up.
    Nature Reviews Endocrinology 07/2012; 8(10):612-22. · 11.03 Impact Factor
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    ABSTRACT: Parathyroid cancer is rare and often has a poor outcome. There is no classification system that permits prediction of outcome in patients with parathyroid cancer. This study was designed to validate two prognostic classification systems developed by Talat and Schulte in 2010 ("Clinical Presentation, Staging and Long-term Evolution of Parathyroid Cancer," Ann Surg Oncol 2010;17:2156-74) derived from a retrospective literature review of 330 patients. This study contains 82 formerly unreported patients with parathyroid cancer. Death due to disease was the primary end point, and recurrence and disease-free survival were the secondary end points. Data acquisition used a questionnaire of predefined criteria. Low risk was defined by capsular and soft tissue invasion alone; high risk was defined by vascular or organ invasion, and/or lymph node or distant metastasis. A differentiated classification system further classified high-risk cancer into vascular invasion alone (class II), lymph node metastasis or organ invasion (class III), and distant metastasis (class IV). Statistical analyses included risk analysis, Kaplan-Meier analysis, and receiver-operating characteristic (ROC) analysis. Follow-up ranged 2-347 months (mean 76 months). Mortality was exclusive to the high- risk group, which also predicted a significant risk of recurrence (risk ratio 9.6; 95% confidence interval 2.4-38.4; P < 0.0001), with significantly lower 5-year disease-free survival (χ(2) = 8.7; P < 0.005 for n = 45). The differentiated classification also provided a good prognostic model with an area under the ROC curve of 0.83 in ROC analysis, with significant impairment of survival between classes (98.6%, 79.2%, 71.4%, 40.0%, P < 0.05 between each class). This study confirms the validity of both classification systems for disease outcome in patients with parathyroid cancer.
    Annals of Surgical Oncology 03/2012; 19(8):2620-8. · 4.12 Impact Factor
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    ABSTRACT: We undertook a systematic review of 404 published cases of Castleman's disease to identify the role of the surgeon beyond assistance in tissue-based diagnosis. Castleman's disease is a rare primary disease of the lymph node caused by infection with herpesviridae. Little is known about the role of surgery in this condition. Medline, Embase, Cochrane Database of Systematic Reviews, ISI Thompson Web of Knowledge, and hand search of articles' bibliography. Of the 1791 citations identified through the initial electronic search and screened for possible inclusion, 488 articles were retained after title and abstract reviews. Of these, 239 were accepted for this review. A complete dataset containing age, gender, centricity (unicentric vs multicentric), histopathologic type (hyaline vascular [HV] vs plasma cell [PC]), anatomical location of the only focus in unicentric Castleman's disease (UCD) or the dominant focus in multicentric Castleman's disease (MCD), nature of the surgical approach (resective vs diagnostic), and outcome (disease-free survival [DFS] vs death due to disease) was extracted. A resective or debulking surgical approach was described in 77.0% of all patients, but was far more common in unicentric (262/278; 94.2%) than multicentric (49/126; 38.9%) disease (χ² 146.8; P < 0.0001). Unicentric disease had a significantly higher overall survival (95.3% vs 61.1%; χ² 55.7; P < 0.0001), 3 year DFS (89.7% vs 55.6%; χ² 27.8; P < 0.0001), and 5 year DFS (81.2% vs 34.4%; χ² 28.6; P < 0.0001) than multicentric disease. Failure to treat unicentric disease by resective surgery resulted in a significant mortality (17.6% vs 3.8% χ²; P < 0.05). In multicentric disease, outcomes are comparable between debulking surgery alone, immunochemotherapy alone, or a combination of both (28.0% vs 28.9% vs 50.0%; P = nonsignificant). Surgery is the gold standard for treatment of unicentric Castelman's disease. The role of debulking surgery in human immunodeficiency virus (-) MCD needs to be evaluated in prospective studies.
    Annals of surgery 02/2012; 255(4):677-84. · 7.90 Impact Factor
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    ABSTRACT: Inflammatory disorders of the parathyroid gland are very rare as compared with those of other endocrine organs. The aim of this study was to provide the first systematic review of this condition. A 42-year-old patient underwent surgery for recurrent secondary hyperparathyroidism. Histology showed hyperplastic parathyroiditis defined by a mixed inflammatory infiltrate with active germinal centres. Molecular markers revealed significant upregulation of CD68 in an ischaemic background (hypoxia-inducible factor 1 upregulation) with mitochondrial reaction (malate dehydrogenase 2 upregulation) and hyperparathyroidism (carbonic anhydrase 4 upregulation). Our case demonstrates true intraparathyroid inflammation with terminal B-cell differentiation. We searched PubMed, ISI Thompson and Google Scholar up to January 2011, using the terms 'parathyroiditis', 'inflammation of parathyroid gland', 'lymphocytic infiltrate', 'tuberculosis of the parathyroid', 'sarcoidosis', and 'graulomatous inflammation'. Three autopsy series, 27 articles and 96 case reports with inflammatory parathyroid disorders were identified. Autopsy series showed lymphocytic infiltrates in up to 16% of all cases. The entire material reported lymphocytic infiltrates (n=69), parathyroiditis with germinal centres (n=15), sarcoidosis (n=6), tuberculosis (n=4), and other granulomatous diseases (n=2). Distinct inflammatory and granulomatous processes in the parathyroid gland are rare. Scanty lymphocytic infiltrates are common, and occur in generalized inflammatory conditions or venous congestion. We note the surprising absence of an association between histological proof of parathyroiditis and hypoparathyroidism.
    Histopathology 11/2011; 59(5):897-908. · 2.86 Impact Factor
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    Nadia Talat, Klaus-Martin Schulte
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    ABSTRACT: Castleman's disease is a rare primary disease of the lymph nodes with limited available clinical information. A systematic literature search identified 416 cases amenable to detailed analysis. In HIV(-) patients, centricity, pathology type, the presence of symptoms, gender, and age all predict outcome in univariate analyses. The 3-year disease-free survival (DFS) rate for patients with unicentric hyaline vascular disease (49.5% of cases, class I) was 92.5%, versus 45.7% for those with multicentric plasma cell disease (20.2% of cases, class III) and 78.0% for those with any other combination (22.6% of cases, class II) (p < .0001). HIV(+) patients (class IV) exclusively presented with multicentric plasma cell disease and had a 3-year DFS rate of only 27.8%. Kaposi's sarcoma and lymphoma were observed in 59.3% and 9.4% of HIV(+) patients and in 2.6% and 3.6% of HIV(-) patients (p < .0001). Paraneoplastic pemphigus and the syndrome of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes were observed exclusively in HIV(-) patients at a rate of 1.3% and 1.8%, respectively. Clinical, pathological, and viral markers allow for the classification of Castleman's disease into groups with markedly different outcomes and disease associations.
    The Oncologist 07/2011; 16(9):1316-24. · 4.10 Impact Factor
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    ABSTRACT: Nearly all reported parathyroid cancers are >15 mm at presentation. The objective was to identify ultrasound criteria of malignancy in parathyroid lesions of >15 mm in size. This study was approved by a local ethics committee. A retrospective review of patients identified from a database from 2004-2009 was performed. All patients underwent ultrasound imaging according to the protocol. Two trained observers categorized findings using the pre-determined features: shape, calcification, pattern of vascularity, local infiltration and internal lesion gray scale appearances. Sixty-nine patients (mean age 54.3 years, range 19-79 years; male = 16, female = 53) fulfilled the criteria of a parathyroid lesion >15 mm; 8/69 (11.6%) with parathyroid cancer and 61/69 (88.4%) with benign solitary parathyroid adenoma. A high positive predictive value (PPV) for cancer was identified for infiltration (PPV 100%) and calcification (PPV 100%), whilst a high negative predictive value (NPV) was found for the absence of suspicious vascularity (NPV 97.6%), a thick capsule (NPV 96.7) and inhomogeneity (NPV 100%). In lesions >15 mm systematic ultrasound assessment of specific features provides a valuable tool to identify parathyroid cancers before surgery.
    European Radiology 05/2011; 21(9):1865-73. · 3.55 Impact Factor
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    ABSTRACT: A 78-year-old woman with B-symptoms was referred for a left adrenal incidentaloma of 5 cm. Imaging revealed features compatible with adrenal cancer. The authors excluded excess production of catecholamines or adrenal steroids. The tumour was removed by en bloc radical left retroperitonectomy with adrenalectomy, nephrectomy, interaortocaval lymphadenectomy and splenectomy. Histology demonstrated periadrenal hyaline vascular Castleman's disease with local infiltration and 14 positive lymph nodes. The lymphoid infiltrate spilled into the adjacent renal cortex. HHV8 was negative. The Ki67 proliferative index was 30-40% in germinal centres. There was no syn- or metachronous disease on extended imaging including fluorodeoxyglucose positron emission tomography-CT and narrow follow-up at 3 years. This is a rare case of unicentric hyaline vascular Castleman's disease with documented locoregional lymph node involvement. The case exemplifies the transition from unifocal unicentric disease into disseminated disease with involvement of multiple lymph node stations (multicentric disease). The authors demonstrate surgical cure by oncological resection.
    Case Reports 01/2011; 2011.
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    ABSTRACT: The best surgical approach to parathyroid cancer is disputed. Recommendations vary and are built on incoherent evidence. High rates of recurrence and death require an in-depth review of underlying findings. This retrospective study includes 11 patients with parathyroid cancer who underwent surgery with central and/or lateral neck dissection by a single surgeon between 2005 and 2010. The diagnosis was based on histopathological criteria in all patients. Patterns of lymph node and soft tissue involvement of these and formerly reported patients were analysed based on full-text review of all published cases of parathyroid cancer. In this series only 1 of 11 patients (9.1%) manifested lymph node metastasis. In the literature, lymph node metastases have been reported in only 6.5% of 972 published patients, or in 32.1% of the 196 in whom lymph node involvement was assessed by the authors. They were, with few exceptions, localised in the central compartment. Recurrence in soft tissue is more frequent than in locoregional lymph nodes. Oncological en bloc clearance of the central compartment with meticulous removal of all possibly involved soft tissues, including a systematic central lymph node resection, may improve outcomes and should be included in the routine approach to the suspicious parathyroid lesion. There is no need for a prophylactic lateral neck dissection.
    World Journal of Surgery 11/2010; 34(11):2611-20. · 2.23 Impact Factor
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    ABSTRACT: Germline missense mutations of the RET protooncogene cause a clinical spectrum called multiple endocrine neoplasia (MEN) type 2. A strong genotype-phenotype correlation results in major implications for the clinical approach. More information on less common mutations is needed to advance specific guidance. We report individualized patient information on 36 carriers of the intracellular RET gene mutation S891A from three centers and clustered data of 38 former patients reported in the literature in nine additional studies. S891A mutation accounts for up to 5% of all patients to date reported with RET mutations and 16% of those hitherto reported with intracellular mutations. S891A mutation caused medullary thyroid cancer (MTC) in 69.4%, pheochromocytoma in 2.8%, and parathyroid hyperplasia in 8.3% of the 36 patients of this case series and in 63.5, 4.1, and 4.1%, respectively, for the entire groups of 74 patients. The youngest age of onset for MTC in this group was 17 yr (median, 46 yr; range, 17-80 yr), for pheochromocytoma 46 yr (median, 46 yr), and for parathyroid hyperplasia 17 yr (median, 20 yr, range, 17-46 yr). Persistence of MTC was described in 14.3% of patients with available follow-up. Additional findings included corneal nerve thickening in three of 74 patients (4.1%). This intracellular mutation can initiate the full spectrum of MEN2a, initiates MTC at an early age, and causes recurrence and death if undertreated. We recommend stringent adherence to established guidance in MEN2a in this rare mutation.
    The Journal of clinical endocrinology and metabolism 09/2010; 95(9):E92-7. · 6.50 Impact Factor
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    Klaus-Martin Schulte, Nadia Talat
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    ABSTRACT: Castleman's disease is a primary infectious disease of the lymph node that causes local symptoms or a systemic inflammatory syndrome. Histopathology reveals a destroyed lymph node architecture that can range from hyaline-vascular disease to plasma-cell disease. Viral interleukin 6 (vIL-6) produced during the replication of human herpesvirus type 8 (HHV8) is the key driver of systemic inflammation and cellular proliferation. Stage progression of Castleman's disease results from switches between viral latency and lytic replication, and lymphatic and hematogenous spread. Multicentric plasma-cell disease in HIV-1 patients is associated with HHV8 infection. Polyclonal plasmablast proliferation escapes control in the germinal center with eventual malignant transformation into non-Hodgkin lymphoma. Surgery produces excellent results in unicentric disease, while multicentric disease responds to anti-CD20 therapy or IL-6 and chemotherapy. Lymphovascular endothelium and naive B cells are infectious reservoir-opening options for antiangiogenic and anti-CD19 strategies to enhance outcomes in patients with systemic disease.
    Nature Reviews Clinical Oncology 09/2010; 7(9):533-43. · 15.03 Impact Factor
  • Nadia Talat, Klaus-Martin Schulte
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    ABSTRACT: Parathyroid cancer is rare and often fatal. This review provides an in-depth analysis of 330 clinical cases reported in detail. These data are used to inform a proposal for a hitherto lacking TNM staging system. All case reports or series with sufficient case details of parathyroid cancer were identified from PubMed, and data were analyzed using SPSS. Of 330 patients, 117 (35%) died of disease and 207 (63%) experienced recurrence in a total of 2007 follow-up years and a mean length of follow-up of 6.1 years. Histopathology findings rather than biochemical or clinical features predict outcome. In univariate analysis, survival and recurrence rates are significantly influenced by gender (male relative risk [RR] 1.7, 95% confidence interval [95% CI] 1.0-2.7, P < .01), and presence of vascular invasion (RR 4.3, 95% CI 1.1-17.7, P < .01), or lymph node metastases (RR 6.2, 95 %CI 0.9-42.9, P < .001). Failure to perform oncological surgery carries a high risk for recurrence and death (local versus en bloc resection RR 2.0, CI 1.2-3.2, P < .01) as for redo surgery. Staging by a novel anatomy-based TNM system identifies significant outcome variation as to recurrence and death. Separation of patients into low and high risk identifies a 3.5-7.0 fold higher risk of recurrence and death (P < .01) for the high-risk group. Distant metastases predominantly target mediastinum and lung. Understaging and undertreatment are shown to contribute to high recurrence rates and death toll. To improve outcome, en bloc resection including central lymph node dissection should be the minimal surgical approach in any patient with suspected parathyroid cancer.
    Annals of Surgical Oncology 03/2010; 17(8):2156-74. · 4.12 Impact Factor

Publication Stats

79 Citations
74.71 Total Impact Points

Institutions

  • 2011
    • King's College Hospital NHS Foundation Trust
      • Department of Radiology
      London, ENG, United Kingdom
  • 2010
    • King's College London
      Londinium, England, United Kingdom