Role of Genetic Testing in the Management of Indeterminate Thyroid Nodules in the Indian Setting.

The increased detection of thyroid nodules in the human population has led to an increase in the number of thyroid surgeries without an improvement in survival outcomes. Though the choice for surgery is straightforward in malignant thyroid nodules, the decision is far more complex in those nodules that get categorized into indeterminate thyroid nodules (ITN) by fine needle aspiration. Therefore, there is a pressing need to develop a tool that will aid in decision-making among the ITN. In this context, the development of various molecular testing (MT) panels has helped to confirm or rule out malignancy, reducing unnecessary surgeries and potentially guiding the extent of surgery as well. Currently, such tests are widely used among the Western population but these MT panels are not used by the South Asian population because of non-availability of validated panels and the high cost involved. There is a need to develop a suitable panel which is population-specific and validate the same. In this review, we would focus on current trends in the management of ITN among the South Asian population and how to develop a novel MT panel which is cost-effective, with high diagnostic accuracy obviating the need for expensive panels that already exist.

Comparative analysis of mutational patterns in triple negative breast cancer before and after neoadjuvant chemotherapy in patients with residual disease.

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.

Dose-Dense Docetaxel-Cyclophosphamide and Epirubicin-Cisplatin(ddDCEP): Analysis of an Alternative Platinum-Containing Regimen in 116 Patients with Early Triple Negative Breast Cancer.

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.

Effectiveness of a monitored home isolation program for COVID-19 infection during the second wave of the pandemic.

Background: The rapidity of spread of COVID-19 infection during the second wave of the pandemic placed tremendous stress on healthcare resources. This study evaluated the effectiveness of a monitored home isolation (HI) program. Methods: In this descriptive longitudinal study, symptomatic patients were screened in the HI clinic and eligible patients were followed up at home using tele-consultation, until recovery or hospitalization. HI failure was defined as need for hospitalization. Factors associated with HI failure were assessed using logistic regression analysis and expressed as odds ratio (OR) with 95% confidence interval (CI). Results: During April and May 2021, 1957 RT-PCR confirmed patients (984 male) with mean (SD) age 40 (13.5) years were enrolled; 93.3% (n = 1825) were successfully managed at home. Of the 132 patients (6.7%) who failed HI, 57 (43.2%) required oxygen therapy and 23 needed intensive care admissions. Overall mortality was 0.4% (7/1957). On adjusted analysis, factors associated with HI failure were age ≥60 years (OR 2.24; 95%CI 1.26-3.99), male gender (OR 2.26; 95%CI 1.44-3.57), subjective reporting of breathing difficulty (OR 3.64; 95%CI 2.08-6.37), history of cough (OR 2.08; 95%CI 1.37-3.17), and higher heart rate (OR 1.04; 95%CI 1.02-1.05). Although patient status (non-healthcare workers), no prior vaccination and ≥2 comorbidities were associated with HI failure on unadjusted analysis, these were non-significant on adjusted analysis. Conclusion: Monitored HI program can be used successfully during a pandemic wave to judicially use scare hospital resources. Older male patients presenting with breathlessness or cough may warrant closer monitoring.

Adrenocortical Carcinoma: a Therapeutic Challenge - 44 Cases from a Single Tertiary Care Center in India.

This study was conducted among patients with adrenocortical carcinoma (ACC) to analyze their clinico-pathological profile, management outcomes, and risk factors for local recurrence, systemic metastasis, and survival. The data of patients with ACC who were managed at a single institution between January 2004 and December 2016 was retrospectively collected and analyzed using STATA 13.1. Forty-four patients with a diagnosis of ACC were included in the study. The mean age at presentation was 38.5 ± 14.6 (9-74) with a male preponderance. Functioning tumors represented 59.1% (n = 26), cortisol being the most common hormone secreted. Forty patients (90.9%) underwent surgery, 14 (35%) of whom required an en bloc resection of adjacent organs. Fifteen (37.5%) received radiation (RT) to the postoperative bed while chemotherapy and mitotane were administered in 12 (27.3%) and 9 (20.5%) respectively. The mean follow-up was 34.3 ± 32.7 months. Twelve (30%) patients developed local recurrence, 21 (55.3%) had systemic metastasis, and 15 (34.1%) expired. The mean 1-year and 5-year overall survival rates were 77% and 65.7% respectively. On multivariate analysis, patients with ENSAT stage III/IV were significantly associated with local recurrence (p = 0.011) and metastasis (p = 0.037). Age > 50 (p = 0.003) and ENSAT III/IV (p = 0.017) were significantly associated with mortality on univariate analysis but not on multivariate analysis. In our study population, patients presented at a younger age with a male preponderance. Ninety percent underwent surgery, a subset (35%) requiring resection of adjacent organs to ensure R0 resection. Patients presenting at ENSAT stage I/II have better outcomes.

Laryngotracheal Resection in Thyroid Cancer - Experience from a Single Centre Series of 22 Cases.

Involvement of the aerodigestive tract is reported in one-third of patients with locally invasive thyroid cancer. It is associated with significant morbidity and mortality, with airway obstruction being the immediate cause of death in 50% of patients who die of thyroid cancer. Management is challenging and includes the risks of extensive surgery as well as decisions regarding the type of surgery and adjuvant therapy. Retrospective cohort study, reporting institutional experience with patients who underwent laryngotracheal resection for invasive thyroid cancer over the past 10 years. Twenty-two patients were included in the study. All patients had Shin stage 4 disease. The median follow-up was 18 months. Five patients had systemic metastasis at diagnosis. Nineteen patients underwent tracheal resection and end to end anastomosis, and 3 underwent laryngectomy. The mean length of the resected trachea was 2.94 cm. Tracheal releasing manoeuvres were utilized in 11 patients. Three patients required a tracheostomy postoperatively. Other complications included a temporary vocal cord palsy in 5 patients, temporary hypocalcemia in 6 and permanent hypocalcemia in 1 patient. Adjuvant radiotherapy was utilized in 9 patients and I-131 therapy in 13 patients. Three patients died during follow-up. Two patients developed thyroid bed recurrence, two patients developed systemic metastasis on follow-up. Most patients survived for a prolonged period with only biochemical evidence of disease persistence and three with no evidence of disease. Laryngotracheal resection with primary anastomosis is a safe and effective option, providing adequate symptomatic relief as well as prolonged survival in carefully selected patients with invasive Shin stage 4 disease.

Time to Revisit a Low-Cost Alternative? Palpation Assessment Nerve Monitoring (PANM) for Recurrent Laryngeal Nerve to Predict Postoperative Vocal Cord Function-a Validation Study Using an In-House Neuromonitoring Device.

Neuromonitoring has proved to be a useful technique in reducing nerve injury during thyroid surgery; however, costs continue to limit its use in resource-constrained settings. This study was done to assess the functional integrity of the recurrent laryngeal nerve (RLN) during thyroid surgery using palpation assessment of posterior cricoarytenoid muscle twitch in response to RLN stimulation. Between August 2016 and July 2017, 24 patients with 47 nerves at risk (NARs) underwent thyroid surgery with visual identification and testing of 44 RLNs. The functional integrity of the RLN was checked by stimulation of the RLN. Intraoperative assessment showed 100% sensitivity and positive predictive value in predicting postoperative vocal cord function. The postoperative vocal cord assessment confirmed all 44 nerves tested to be normally functioning. The mean (standard deviation) peak-to-peak amplitude and latency of the CMAP were 0.889 (0.740)/1.336 (1.660) mV and 2.295 (0.319)/2.217 (0.393) ms for left/right side NARs, respectively, with no statistically significant difference (P > 0.05). Palpation assessment of the posterior cricoarytenoid muscle provides a simple and reliable technique for confirming integrity of the RLN. Combining palpation assessment with CMAP from the inferior constrictor muscle may help reduce potential false negative results. With the use of our in-house built device which is significantly cheaper than the commercial ones, this could be considered a low-cost alternative to current established techniques.

Impact of thyroidectomy on quality of life in benign goitres: results from a prospective cohort study.

PURPOSE: Benign thyroid diseases encompass a large spectrum of conditions that are chronic and subtle in nature. A majority of patients choose non-surgical management and continue living their daily lives with subconscious impairment of optimal functioning. We studied the effect of thyroidectomy on the quality of life (QoL) in patients with benign goitres. METHODS: A prospective study was conducted on 50 patients between January 2017 and August 2018 using the ThyPRO 39 questionnaire. This is a disease-specific health-related questionnaire administered the day before surgery and 6 months following surgery. Data analysis was performed using EpiData Manager and EpiData Entry Client (v 3.1). RESULTS: The mean age of the cohort was 43.30 years ± 11.61, with a female preponderance (34:16). The most common indications for surgery were suspicion of malignancy and compressive symptoms in 34% and 30%, respectively. The most common histopathology reported was nodular/adenomatous hyperplasia (56%). Prior to surgery, the most common domains affected were emotional susceptibility and tiredness. Following surgery, a significant improvement in all domains of the ThyPRO 39 questionnaire were seen except for psychological well-being (p=0.126). In addition, the composite scores significantly improved (p<0.001). Younger age, female gender, and longer duration of goitre were the factors that significantly affected the outcomes in various domains. CONCLUSION: Patients with benign goitres have subtle impairment of QoL which showed significant improvement following thyroidectomy.

The utility of indocyanine green (ICG) for the identification and assessment of viability of the parathyroid glands during thyroidectomy.

We conducted this study to evaluate the ability of indocyanine green (ICG) and near infra-red fluorescence (NIRF) camera to aid in the identification and assessment of viability of parathyroid glands during thyroid surgery. A prospective observational study was conducted between May and October 2020 among 50 consecutive patients who underwent total thyroidectomy at a single institution. Parathyroid glands were identified under white light during thyroidectomy following which reconstituted ICG was injected through a peripheral vein and the location of parathyroid glands was confirmed. The perfusion to the parathyroid gland was assessed by documenting the fluorescence intensity score (FIS) and the parathyroid angiogram score (PAS). There was no difference in the number of parathyroid glands seen on visual inspection 147 (73.5%) when compared to under NIRF camera, 146 (73%). Though the rate of postoperative hypoparathyroidism was lower in the cohort with FIS 3 (14.2%) compared to score 2 and 1 (28.5% and 100%, respectively), this was not significant (p = 0.35). A significant correlation was noted between a delayed flow on PAS and the development of post-thyroidectomy hypoparathyroidism (p = 0.01). PAS had a sensitivity of 100%, specificity of 88.6%, NPV of 100% and PPV of 55.6% to predict the development of post-thyroidectomy hypoparathyroidism. In this study, there was no additional benefit of ICG and NIRF camera in the identification of parathyroid glands. However, ICG angiogram seems to be a good adjunct for the intraoperative assessment of the viability of the parathyroid glands and accurately predicts the development of postoperative hypoparathyroidism.

Myelofibrosis and Pancytopenia Associated With Primary Hyperparathyroidism.

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.

Neoadjuvant chemotherapy with biosimilar trastuzumab in human epidermal growth factor receptor 2 overexpressed non-metastatic breast cancer: patterns of use and clinical outcomes in India.

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.

Clinical Profile and Mutations Associated with Multiple Endocrine Neoplasia-Type1 (MEN1) and Their First-Degree Relatives at Risk of Developing MEN1: A Prospective Study.

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.

Sentinel Lymph Node Biopsy in Early Breast Cancer Using Methylene Blue Dye Alone: a Safe, Simple, and Cost-Effective Procedure in Resource-Constrained Settings.

Sentinel lymph node biopsy (SLNB) is done by different techniques in clinically node-negative patients with early breast cancer. In this study, we aim to estimate the identification rates, positivity rates, cost-effectiveness, and outcomes for patients who underwent sentinel node biopsy using methylene blue dye alone. This was a retrospective review of 172 patients with early breast cancer (cT1-3, N0) who underwent SLNB using methylene blue dye alone between January 2014 and December 2018 including their follow-up details until December 2019. The mean age was 51 ± 10.3 (range: 28 to 76) years. There were 63 (36.6%) patients with cT1 tumor, 108 (62.7%) with cT2, and only 1 patient with cT3 tumor. Breast conservation surgery was performed in 62 (36%) while the remaining 110 (64%) underwent simple mastectomy. Sentinel nodes were successfully identified in 165 (95.9%) with a positivity rate of 23.6%. There was no dye-related adverse reactions intra-operatively. The mean duration of follow-up was 26.68 ± 15.9 months (range: 1-60). Chronic arm pain was present in 7 (4%) while none of the patients had lymphedema or restriction of shoulder joint motion. There were no documented axillary nodal recurrences in this cohort. Eight (4.65%) patients were detected to have systemic metastasis. One patient died of brain metastasis from bilateral breast cancer. The mean disease-free survival was 57 months (95% CI: 55-59). Sentinel lymph node biopsy using methylene dye alone is a safe, simple, and cost-effective alternative to isosulfan blue or radio isotope technique in surgical centers with resource constraints.

Papillary Thyroid Carcinoma in Children: Clinicopathological Profile and Outcomes of Management.

BACKGROUND: We aim to analyze the clinicopathological profile and outcomes of management for children with papillary thyroid carcinoma (PTC). METHODS: Relevant clinical data of children ≤ 18 years of age managed for PTC between January 2006 and July 2018 as well as details of their follow-up till December 2019 were retrospectively collected and analyzed. RESULTS: There were 82 children with PTC that were managed during the study period. At presentation, 39 (47.6%) had cervical lymphadenopathy, while 9 (11%) had systemic metastasis. Majority of patients 39 (47.6%) underwent total thyroidectomy with a selective neck dissection, while total thyroidectomy alone was performed in 26 (31.7%). Following surgery, hypocalcemia was seen in 39 (47.6%): 28 (34.1%) were temporary, while 11 (13.4%) were permanent. Twenty-eight (34%) developed persistent disease after surgery and 131I therapy. Significant risk factors for persistence and metastatic disease were metastatic cervical lymph node at presentation (p = 0.002) and tumor size (p = 0.014), respectively. The mean duration of follow-up was 60.3 (range 12-150) months with a mean overall disease-free survival of 60 months (95% CI 57.11, 77.95). CONCLUSION: Children with papillary thyroid cancers present with aggressive disease, 47.6% with cervical nodal metastasis and 11% with distant metastasis in this cohort. The rate of post-thyroidectomy hypocalcemia in this study is substantial, and efforts to reduce it are actively being pursued. The presence of metastatic cervical lymph node at presentation (p = 0.002) and tumor size (p = 0.014) were the only significant risk factors for persistent and metastatic disease, respectively, in this study.

The impact of operative duration and intraoperative fluid dynamics on postoperative hypocalcemia after total thyroidectomy: a prospective non-randomized study.

BACKGROUND: Postoperative hypocalcemia after total thyroidectomy (TT) still remains common. This prospective observation study examined the role of intraoperative time period (IOP) and intravenous fluids (IVF) in transient and permanent (> 6 months) hypocalcemia post-TT. SUBJECTS AND METHOD: Consecutive patients (n = 328; age = median (IQR); 34 (15) years; M:F = 65:263) with benign or malignant thyroid disease undergoing TT were evaluated for IOP, intraoperative IVF, serum corrected calcium, intact parathormone (iPTH), and 25-hydroxyvitamin D (25OHD) levels at baseline, 48 h, and 6 months post-TT. RESULTS: The incidence of symptomatic transient and permanent hypocalcemia post-TT was 33.5% and 7.9% respectively. In multivariate logistic regression analysis, the independent risk factors for transient hypocalcemia were IOP (odds ratio: 11.6), 48-h iPTH (4.8), IVF (2.9), hyperthyroidism (2.8), and percent calcium decline (1.07), while 25OHD deficiency increased the risk by 10.5 odds in subset with preoperative hypocalcemia. In receiver operating characteristic analysis, IOP, and IVF strongly predicted transient hypocalcemia with a threshold of 123 min and 1085 mL. Area under the curve, sensitivity, and specificity were 0.883 (95% CI: 0.838-0.928), 88.1%, and 74.4% and 0.883 (0.840-0.926; each P = 0.001), 84.4%, and 74.4% respectively. Serum 48-h calcium < 7.8 mg/dL was the only reliable predictor of permanent hypocalcemia. CONCLUSION: Operative duration > 123 min and IVF > 1085 mL increased the risk of transient hypocalcemia post-TT manyfold but not permanent hypocalcemia. Routine intraoperative identification, preservation of viable in situ parathyroid glands, and laryngeal nerves increased IOP and rates of transient hypocalcemia but improved long-term outcome.

Does Baseline PTH Influence Recovery of Bone Mineral Density, Trabecular Bone Score and Bone Turnover Markers? A Prospective Study Following Curative PArathyroidectomy in Primary Hyperparathyroidism.

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.

The Effect of Hypomagnesemia on Refractory Hypocalcemia after Total Thyroidectomy: A Single-Center Prospective Cohort Study.

BACKGROUND: Hypomagnesemia is known to impede hypocalcemia correction. This prospective observational study aimed to evaluate the impact of serum magnesium levels on the development of refractory hypocalcemia, which remains a concerning problem after total thyroidectomy (TT). SUBJECTS AND METHODS: Consecutive subjects (n = 312; mean age = 38.4 [range: 13-83] years; M:F = 62:250) undergoing TT for benign or malignant thyroid diseases were evaluated for serum corrected-calcium (8.4-10.4 mg/dL), magnesium (1.7-2.4 mg/dL), intact parathormone (iPTH), and 25-hydroxycholecalciferol (25OHD) levels preoperatively, at 48-h and 6-month post-TT. RESULTS: Postoperatively, 98 subjects (31.4%) exhibited transient hypocalcemia, 96 (30.8%) had hypomagnesemia, and 52 (16.7%) had refractory hypocalcemia. Preoperatively, 38 subjects (12.2%) had asymptomatic hypocalcemia and 77 (24.7%) had hypomagnesemia. In multivariate logistic regression analysis, independent risk factors of transient hypocalcemia were hyperthyroidism (odd's ratio [OR]: 5.6), 48-h iPTH (OR: 3.2), 48-h magnesium (OR: 2.7), preoperative 25OHD (OR: 0.96), and preoperative calcium (OR: 0.5; each P < 0.01). In receiver-operating characteristic analysis, percent calcium decline and 48-h magnesium reliably predicted transient hypocalcemia with a threshold of 10.5% and 1.9 mg/dL, respectively. Area under curve, sensitivity, and specificity were 0.822, 82.7%, and 72.9%; and 0.649 (each P < 0.001), 68.4%, and 63.1%, respectively. CONCLUSION: Serum magnesium below 1.9 mg/dL had 2.7 times higher odds of developing transient hypocalcemia post-TT. Hypomagnesemia and percent calcium decline >10.5% within 48-h post-TT are associated with refractory hypocalcemia, which necessitates correction of both the deficiencies for prompt resolution of symptoms.

Focused Parathyroidectomy Under Local Anesthesia - A Feasibility Study.

PURPOSE: We conducted this study to evaluate the feasibility, patient satisfaction, and cost of performing focused parathyroidectomy under local anesthesia (LA) and mild sedation, administered and monitored by a surgeon. MATERIALS AND METHODS: This was a prospective observational study of 30 patients with primary hyperparathyroidism (PHPT) undergoing a focused parathyroidectomy under LA and mild sedation at a single institution. The clinical features, gland weight, operating time, procedure time, postoperative pain scores, overall patient satisfaction, postoperative nausea and vomiting, analgesic requirements, complications, cost, and cure rates were documented. Data were analyzed using SPSS software version 17.0. RESULTS: In two patients (6.7%), the procedure had to be completed under general anesthesia (GA). Postoperative temporary hypocalcemia was witnessed in 14 of 30 (46.7%), but only 1 required intravenous calcium infusion. About 21 of 30 (75%) were completely satisfied with LA, whereas 25 of 30 (89%) were completely satisfied with surgical procedure. Furthermore, all patients were keen to recommend this procedure under LA to their friends and family. Comparing the cost between performing the procedure under LA with that under GA, a significant difference was witnessed (P = 0.001). Among the 26 patients reviewed at 6 months, all had a normal serum calcium and parathyroid hormone levels indicating 100% cure rate. CONCLUSION: Performing focused parathyroidectomy under LA is feasible; additionally, this method can significantly reduce the cost of the procedure (P = 0.001).

An Insight into the Utility of Sub-Categorisation of Atypia of Undetermined Significance for Risk Stratification: A Retrospective Study on an Indian Cohort with Histopathological Correlation.

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.

Re-operative Surgery for Pheochromocytoma-Paraganglioma: Analysis of 13 Cases from a Single Institution.

Re-operative adrenal surgery for recurrent pheochromocytoma/paraganglioma (PCC/PGL) is a therapeutic situation not commonly encountered. The recurrence rate of pheochromocytoma is estimated to be 6.1-16.5% of patients from published retrospective series; there are no reports from the Asian continent. A retrospective analysis of the departmental database was performed on patients who had undergone surgery for PCC/PGL from January 2004 to December 2014 at the Christian Medical College Hospital, Vellore, India. Among 99 patients identified during the study period, there were 14 recurrent tumours and 13 patients underwent re-operative surgery. We located eight recurrences on the right side, three on the left side and three in the midline. All 14 recurrences were functioning, and the biochemical analysis as well as imaging studies were positive in 13 of them. The mean duration to recurrence from the time of the primary surgery was 76.3 months (range 6-180 months). Of the 89 patients who underwent their first operation at our centre, 67.4% reported for follow-up for a mean period of 25 months (range 4-132 months). Four of these required re-operation with a recurrence rate of 4.5% (4/89). The open approach was used for all but one of the recurrent tumours. Recurrence following surgery for PCC/PGL is a rarely studied though significant problem. Right adrenal tumour recurrences were most common, and all these recurrences were in the retrocaval region; this typical phenomenon may be dubbed the 'right retrocaval trap'. The reason for this was presumably due to difficult access and inadequate exposure of this area in open and laparoscopic surgery, resulting in incomplete dissection.