Clinico-pathologic profile and outcomes of pediatric endocrine patients managed by endocrine surgeons: Experience over three decades in a tertiary center in India.

BACKGROUND: Pediatric endocrine disorders requiring surgical intervention are rare and so are experienced surgeons dealing with these. The aim of the current study was to investigate disease profile and perioperative outcome of pediatric patients with surgical endocrine disorders in an endocrine surgery unit. METHODS: This retrospective study (Sep 1989-Aug 2019) consisted of pediatric endocrine surgery patients (<18 years) who were managed by a team of pediatric endocrinologists and endocrine surgeons at our center. Patients were divided into three cohorts consisting of a decade each. Clinico-pathologic variables, perioperative events operative and follow-up details were recorded. RESULTS: A total of 332 children were included and their mean age was 14.6 ± 3.9 years (M:F = 1:1.6). Thyroid disorders were most prevalent (59.8%), followed by adrenal (28.2%), parathyroid (10.4%), and pancreas (1.5%). Incidence of benign, malignant, and congenital/developmental disorders were 65.4, 28.1 and 8.3, respectively. Familial association was observed in 8.9% children, which is highest among pheochromocytoma patients. Overall, 201 thyroidectomies + associated procedures, 35 parathyroidectomies, 96 adrenal and paraganglioma resections, and 5 pancreatic procedures were performed. Median hospital stay was 5.6 ± 4.1 days. The number of cases increased significantly over 3 decades. Clinical profile and outcome did not vary except for significant decrease in incidence of malignant pathology (p = 0.04) and increase in VHL cases (p = 0.04) in the last decade though overall increase in familial cases was nonsignificant (p = 0.11). No perioperative mortality was observed except for 3% after adrenalectomy. CONCLUSION: A team of dedicated endocrine surgeons and pediatric endocrinologists is effective in management of pediatric endocrine surgery.

Predictive and Prognostic Role of Tumor-Infiltrating Lymphocytes in Patients with Advanced Breast Cancer Treated with Primary Systemic Therapy.

INTRODUCTION: Tumor-infiltrating lymphocytes (TILs) are gaining recognition as an important immunological biomarker with therapeutic potential in breast cancer. In this cohort study conducted on patients with advanced breast cancer treated with primary systemic therapy (PST), the TILs concentration was correlated with response to PST and survival outcomes. METHODS: Patients with primary breast cancer treated with PST between 2016 and 2020 were included in this study, approved by IEC, and registered on ClinicalTrials.gov (NCT05250336). Tumor core biopsies obtained prior to starting treatment from 489 patients were assessed for the proportion of stromal TILs by standardized method and categorized into low (0-10% immune cells), intermediate (11-59%), and high (≥ 60%) TILs. TIL concentration and complete pathological response (pCR), disease-free survival (DFS), and overall survival (OS) were correlated. RESULTS: Of the 489 patients, 372 matched the eligibility criteria for assessment of TILs and made the final study cohort. Among these, 135 were luminal, 129 HER2-enriched, and 108 triple-negative breast cancers (TNBC). Proportions of patients with high TILs were greater in TNBC (15.7%) and HER2-enriched (9.3%), compared to luminal cancers (4.4%). High TIL concentration was correlated with higher pCR in all subtypes. A pCR was achieved in 33.3, 50, and 52.9% of high TIL patients in luminal, HER2-enriched, and TNBC subtypes, respectively (p < 0.05). High TILs were linked to longer DFS and OS in TNBC and HER2-enriched breast cancers. CONCLUSION: In this first study of its kind from a low- and middle-income country, high TILs concentration was found to be a predictor of response to PST across all breast cancer subtypes. TILs concentration was found predictive of better DFS and OS in TNBC and HER2-enriched cancers. Prognostic role of TILs in luminal cancers was not so apparent.

Cost-Efficacy Analysis of Use of Frozen Section Histology for Margin Assessment During Breast Conservation Surgery in Breast Cancer Patients.

BACKGROUND: Margin assessment is an essential component of breast conservation surgery (BCS). Re-excision of infiltrated margin(s) detected on paraffin section histology (PSH) needs reoperation, adding time, inconvenience and cost. Intra-operative assessment of margins using frozen section histology (IFSH) can potentially obviate need for re-operation, thus facilitating one-step oncologically complete BCS. METHODS: IFSH and PSH reports of consecutive patients undergoing BCS (2010-2020) were reviewed. Accuracy and cost-efficacy of IFSH were assessed, considering PSH as gold standard. Cost of achieving oncologically complete BCS in whole cohort with IFSH (Scenario-A) was calculated and compared using appropriate statistical tests, with hospital costs for the cohort in a hypothetical Scenario-B, where IFSH was presumed not to have been used and all patients with infiltrated margin(s) on PSH would have been re-operated. RESULTS: Of the 367 patients screened, 39 were excluded due to incomplete IFSH data. Of 328 patients analyzed, 59 (18%) had one or more margins were reported infiltrated on IFSH, managed by re-excision or mastectomy in the same sitting, thus avoiding a reoperation. Additional 8 (2.4%) had involved margins on PSH (False negative IFSH). Significantly higher number of reoperations (p < 0.001) would have been needed in scenario-B. Average cost of the first operation with use of IFSH was Indian Rupees (INR) 25791 which included INR660 as IFSH cost. The average cost of reoperation was INR23724 which could be avoided in 59 (18%) by use of IFSH. The average cost per patient to achieve oncologically complete surgery in scenario A utilizing IFSH was significantly lower (p = 0.001) by INR3101 (11.7%), c.w. that in scenario B. Significant cost-saving with IFSH was maintained in cost-efficacy analysis undertaken with various higher and lower costs assumptions. CONCLUSIONS: Use of IFSH facilitates one-step oncologically complete BCS in majority of patients and results in considerable cost saving, resulting in avoidance of reoperations, besides preventing patient anxiety and delay in adjuvant treatment. TRIAL REGISTRATION: Clinical Trials Registry-India (CTRI/2021/08/035896).

Cardiac Changes and Their Reversal Following Curative Surgery in Pheochromocytoma: PheoCard Prospective Cohort Study.

BACKGROUND: Pheochromocytoma and paraganglioma (PPGL) are catecholamine producing tumors of chromaffin cell origin, known to cause varied cardiovascular manifestations from hypertension to myocardial infarction. This study sought to objectively evaluate the cardiac changes in PPGL patients and their reversal following curative surgery. METHODS: The PheoCard study was registered in ClinicalTrials.gov (NCT05082311) and involved 35 consecutive PPGL patients managed as per standard protocol involving alpha blockade followed by curative surgery. They underwent detailed cardiac evaluation using 2D-echocardiography and speckle tracking echocardiography at the time of diagnosis, 7-10 days after alpha blockade, and at 7 days, 3 months, and 6 months after surgical removal. Age- and gender-matched essential hypertensives and healthy individuals (10 in each group) served as two control groups. RESULTS: Patients with PPGLs had significantly higher mean blood pressure, left ventricle end-diastolic dimension and volume (LVEDD, LVEDV), left ventricle end-systolic volume (LVESV), septal wall thickness, LV hypertrophy, lower mean LV ejection fraction (LVEF), early diastolic mitral annular velocity (E/A), decreased amplitude of LV longitudinal strain, and increased circumferential strain (p < 0.001) when compared with the control groups at baseline. After alpha blockade, there was marked reduction in the mean LVEDD, LVEDV, LVESV, and normalization of E/A ratio (p < 0.001) in the PPGL patients. Following curative surgery (normalization of fractionated urinary metanephrines at 7-10 days post-operatively), there was early improvement in all echocardiographic parameters and it continued to improve even at 6 months after surgery. There was marked improvement in the global longitudinal strain as seen on serial speckle tracking echocardiography with recovery of most of the segments of LV depicting the reversal of subclinical endocardial dysfunction (p < 0.001). CONCLUSION: PPGL patients despite normal systolic function have subclinical LV diastolic dysfunction which is reversed after curative surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT05082311.

Clinical, Biochemical, Tumoural and Mutation Profile of VHL- and MEN2A-Associated Pheochromocytoma: A Comparative Study.

OBJECTIVE: To compare clinical, biochemical, tumoural and mutational characteristics of Von Hippel Lindau Syndrome (VHL)-associated pheochromocytoma (PCC) to multiple endocrine neoplasia 2A (MEN2A)-associated pheochromocytoma. DESIGN: Retrospective study design in a tertiary health care centre in Northern India. METHODS: A total of 47 patients with biochemical and histologically proven pheochromocytoma/paraganglioma (PCC/PGL): 29 associated with VHL and 18 with MEN2A, were divided in two cohorts, respectively. Analysis of their medical records along with a prospective follow-up was done. RESULTS: There were more children <19 years in VHL group (13 vs 1). Despite majority of VHL-PCC showing elevation of normetanephrine (NMN) (93%) as compared to MEN2A-PCC (22.2%), 75.8% presented with hypertension as compared to MEN2A (33.3%). The average size of VHL-PCC tumours was 5.66 cm. VHL-PCC as compared to MEN2A-PCC were multifocal (75% vs 61.1%), bilateral synchronous (72.4 vs 61.1%) and extra-adrenal (17.2% vs 0%). Both VHL (24%) and MEN2A-PCC (27.7%) showed multiple nodules, but more MEN2A PCC showed extra-tumoural hyperplasia (44.4% vs. 6.8%). In VHL, the commonest mutation (n = 17) was missense mutation with a hot spot on exon 3, while in MEN2A-PCC majority (66.6%) had 634 mutation in exon 11 and only 2 patients had the rare 611 mutation in exon 10. CONCLUSION: In contrast to world literature, our study suggests Indian VHL-PCC can be symptomatic in spite of noradrenergic phenotype, large in size and multifocal. Multiple nodules in VHL-PCC could increase risk of recurrence following subtotal adrenalectomy.

Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy.

Esophageal cancer (EC) is a disease often marked by aggressive growth and poor prognosis. Lack of targeted therapies, resistance to chemoradiation therapy, and distant metastases among patients with advanced disease account for the high mortality rate. The tumor microenvironment (TME) contains several cell types, including fibroblasts, immune cells, adipocytes, stromal proteins, and growth factors, which play a significant role in supporting the growth and aggressive behavior of cancer cells. The complex and dynamic interactions of the secreted cytokines, chemokines, growth factors, and their receptors mediate chronic inflammation and immunosuppressive TME favoring tumor progression, metastasis, and decreased response to therapy. The molecular changes in the TME are used as biological markers for diagnosis, prognosis, and response to treatment in patients. This review highlighted the novel insights into the understanding and functional impact of deregulated cytokines and chemokines in imparting aggressive EC, stressing the nature and therapeutic consequences of the cytokine-chemokine network. We also discuss cytokine-chemokine oncogenic potential by contributing to the Epithelial-Mesenchymal Transition (EMT), angiogenesis, immunosuppression, metastatic niche, and therapeutic resistance development. In addition, it discusses the wide range of changes and intracellular signaling pathways that occur in the TME. Overall, this is a relatively unexplored field that could provide crucial insights into tumor immunology and encourage the effective application of modulatory cytokine-chemokine therapy to EC.

Hereditary Medullary Thyroid Carcinoma: Genotype, Phenotype and Outcomes in a North Indian Cohort.

BACKGROUND: Aggressiveness of hereditary medullary thyroid carcinoma (hMTC) has been conventionally described to correlate with American Thyroid Association (ATA) risk groups based on RET mutations. Recent evidence increasingly contradicts this notion. We studied the RET genotype and its correlation with disease phenotype and survival outcomes in a cohort of hMTC patients. METHODS: In a retrospective cohort of 55 hMTC patients from 23 families treated at a north Indian tertiary care institute over 15-years, RET genotype was correlated with disease phenotype (clinical, biochemical, and pathological attributes) and outcomes in terms of biochemical cure (normalization of serum calcitonin), structural cure, overall survival (OS) and disease specific survival (DSS). RESULTS: Forty-nine patients had Multiple Endocrine Neoplasia (MEN)-type 2A syndrome, 02 had MEN-2B, and 4 had familial MTC. Two patients belonged to highest ATA risk, 41 to high-risk, and 12 to moderate risk categories. Age of the patients or stage of disease at presentation did not differ significantly between the ATA risk groups. Though the baseline serum calcitonin was significantly higher in highest risk category, the biochemical cure rates were not significantly different. At a median follow up of 48 months (Inter-quartile range 18-84, range 12-192) structural cure rates in ATA moderate and high risk groups were significantly higher than highest risk group (p = 0.04). No significant difference in OS between the three ATA groups of hMTC among the patients who underwent surgical treatment was observed (p = 0.098). CONCLUSIONS: The ATA moderate and high risk groups have better structural cure rates compared to ATA highest risk group. The biochemical cure and overall survival rates did not significantly differ between ATA risk-groups, and were impacted by the disease stage at presentation. The current ATA risk-groups do not reliably predict the outcomes in terms of biochemical cure and survival in hMTC patients.

Pediatric Primary Hyperparathyroidism: Experience in a Tertiary Care Referral Center in a Developing Country Over Three Decades.

BACKGROUND: There is limited experience in managing pediatric primary hyperparathyroidism (PHPT). The aim of this study was to analyze the clinical presentation and outcome of surgery in children with PHPT managed at a tertiary referral center. METHODS: This retrospective study (September 1989-August 2019) consisted of 35 pediatric PHPT patients (< 18 years) who underwent parathyroidectomy. Clinico-pathologic profile and outcome were noted. RESULTS: The mean age of cohort was 15.2±2.9 years and girls outnumbered boys (M:F = 1:1.9). Familial and symptomatic disease was noted in 8.5 and 94.3% cases, respectively. Skeletal manifestations (83%) were the commonest followed by renal (29%). Fifty-four percent children had skeletal fractures, and 23% were bed-ridden. Among rare manifestations, hypercalcemic crisis, recurrent pancreatitis and stigmata of rickets were observed in 2.8, 11.4 and 14.2% children, respectively. Mean calcium concentration was 12.1 ± 2.0 mg/dl and PTH 91.8 ± 66.5 pmol/L. The sensitivity of preoperative imaging in parathyroid localization was 91.4%. Minimally invasive parathyroidectomy (MIP) was performed in 40% cases. Parathyroid adenoma was observed in 91.4% patients, whereas remaining had hyperplasia. Thirty-four percent suffered from Hungry bone syndrome in postoperative period. The cure rate following primary surgery was 97%. One child with persistent PHPT had successful re-operation. Median follow-up was 5 (1-17) years, and no recurrence or familial disease was revealed during this period. CONCLUSION: Majority of pediatric patients present with symptomatic PHPT. Despite relatively high incidence of familial disease select pediatric patients can undergo successful MIP.

Molecular xenomonitoring of Dengue, Chikungunya and Zika infections: a year-round study from two Dengue endemic districts of central India.

BACKGROUND & OBJECTIVES: Infections caused by arboviruses and transmitted by Aedes species mosquitoes are a serious health concern. India is endemic for diseases like Dengue, Chikungunya and recently Zika has been reported from few states. Vector control is the only way to contain these diseases, however, data regarding vectors from central India is lacking; to fulfill the lacuna we conducted this study. METHODS: Entomological surveys were conducted from November 2017 to December 2018 for Aedes species in Dengue endemic areas of central India. The mosquitoes were identified, pooled and tested for the presence of Dengue, Chikungunya and Zika viruses by RT-PCR. The PCR products were sequenced to identify serotypes and genotypes of viruses. RESULTS: A total of 2991 adults of Aedes specimens were collected and tested. Ae. aegypti (94.6%) was found to be the most abundant species. Highest mosquito density was recorded in the monsoon periods. Dengue (n=5) and Chikungunya (n=4) virus were detected from pools of female Ae. aegypti. One pool of male Ae. aegypti was positive for Dengue virus-3 and Chikungunya virus. Zika virus was not detected from any pool. INTERPRETATION & CONCLUSION: The findings suggest that Ae. aegypti is the principal vector of Dengue and Chikungunya, which is capable to transmit these viruses vertically. The findings have epidemiological importance and will be helpful to program managers.

Robotic thyroid surgery using bilateral axillo-breast approach: From a trainees' point of view.

BACKGROUND: Across surgical disciplines, the demand for cosmetically superior procedures is stronger than ever and patient-centered health care has become the standard of care. Endoscopic thyroidectomy has revolutionized the field of minimal access endocrine surgery and akin to other surgical disciplines, there has been a natural progression towards robot-assisted thyroidectomy. Amongst the many described approaches, bilateral axillo-breast approach (BABA) and transaxillary are most widely practiced. AIMS AND OBJECTIVES: Our aim was to describe the technique of robot-assisted thyroid surgery (RATS) using BABA. METHODS: This is based on the corresponding authors' training and experience of over 50 cases of RATS using BABA, at the Seoul National University, Republic of Korea. RESULTS: Post-operative outcomes were excellent with lesser pain, better cosmesis and similar oncological outcomes in carefully selected thyroid cancers in comparison to conventional thyroidectomy. CONCLUSION: RATS using BABA is easy to master for endoscopic thyroid surgeons and offers excellent postoperative outcomes, ergonomics, vision and dexterity.

Changing paradigms in endoscopic thyroid surgery: A comparison between scarless-in-the-neck axillo-breast approach and totally scarless transoral approach.

BACKGROUND: To avoid cervical scar in thyroid surgery, various approaches have been proposed. The commonly used approach is combined axillo-breast approach (ABA). However, trans-orovestibular approach (TOVA) is getting popular. The aim of this study is to compare surgical outcomes of patients who underwent endoscopic hemithyroidectomy (EHT) by either ABA or TOVA. PATIENTS AND METHODS: This was a retrospective analysis of clinical data of patients who underwent EHT from January 2013 to December 2018. Patients were divided into two groups: Group A - through ABA and Group B - through TOVA. RESULTS: A total of eighty patients underwent EHT in Group A and 25 in Group B. In both groups, most patients were female (male: female = 1:4.7 in Group A and 1:7.33 in Group B, P = 0.515). In both groups, there was no difference in age (the mean age was 33.44 ± 10.44 years in Group A and 33.04 ± 14.01 years in Group B, P = 0.391) and in size of the nodule (Group A - 3.91 ± 1.17 cm and Group B - 3.6 ± 1.39 cm, P = 0.228). The operating time was significantly less in Group B (Group A - 152.25 ± 30.19 mins and Group B - 126.80 ± 22.94 mins, P ≤ 0.01). The post-operative hospital stay was significantly less in Group B (mean 3.17 ± 0.97 days in Group A and 2.24 ± 0.60 days in Group B, P ≤ 0.01). CONCLUSION: TOVA is associated with shorter operating time and hospital stay with comparable outcomes. Cosmetic outcome is excellent in TOVA, however requires further subjective evaluation.

Endoscopic versus Conventional Thyroid Surgery: A Comparison of Quality of Life, Cosmetic Outcomes and Overall Patient Satisfaction with Treatment.

BACKGROUND: Our aim was to investigate whether the surgical approach, i.e. endoscopic (ET) versus conventional/open thyroidectomy (ConT), contributes towards the improvement in quality of life (QoL), cosmetic outcomes and overall patient satisfaction with treatment. METHODS: We conducted a prospective study (October 2016-August 2018) consisting of patients undergoing hemithyroidectomy for euthyroid, non-malignant solitary thyroid nodules (STNs). Patients were divided into two groups: Group I (ET)-41 patients and Group II (ConT)-52 patients. ET was performed via bilateral-axillo breast approach (BABA). A thyroid disease-specific questionnaire "ThyPRO-39hin" was used to evaluate pre- and post-operative QoL. Visual analogue scale (VAS) was used for post-operative pain. Cosmetic satisfaction, paraesthesia and overall satisfaction with treatment were evaluated using Likert-type verbal response scales. Pre- and post-operative scores (>6 months) were compared, and p value < 0.05 was considered significant. RESULTS: Mean age (p = 0.26), gender distribution (p = 0.07), mean tumour size (p = 0.74) and preoperative scores of QoL were comparable between the two groups. Post-operatively scores of symptom domain (p = 0.03), tiredness (p = 0.03), impaired social life (p = 0.03), cosmetic complaints (p = < 0.001) and overall QoL (p = < 0.001) were significantly better in Group I. Also, post-operative pain perception at first follow-up visit (p = 0.001) was lower in patients undergoing ET/Group I, with higher scar satisfaction scores (p = < 0.001) and overall satisfaction with treatment (p = < 0.001). Post-operative paraesthesia perception was comparable (p = 0.06) amongst the two groups. CONCLUSION: In this cohort study, patients undergoing endoscopic thyroid surgery reported superior post-operative QoL, cosmetic and overall satisfaction with treatment as compared to conventional/open thyroidectomy.

Low-cost Fluorescein as an Alternative to Radio-colloid for Sentinel Lymph Node Biopsy-a Prospective Validation Study in Early Breast Cancer.

BACKGROUND: Sentinel lymph node biopsy (SLNB) using radio-pharmaceutical (RP) and a blue dye is gold standard for axillary staging in clinically node-negative early breast cancer. High costs and limited availability of RP and/or gamma probe are major deterrents in performing SLNB in developing countries. Fluorescence-guided SLNB can obviate the need for RP and gamma probe. Fluorescein is an inexpensive fluorescent lymphatic tracer. In this study, we compared SLN identification rate (SLN-IR) and false negative rates (FNR) of fluorescein-guided SLNB and radio-guided SLNB using 99mTc-Sulfur-colloid, in isolation, or in combination with methylene blue dye (MBD). METHODS: Sixty-five cN0 early and large operable breast cancer patients underwent validation SLNB using fluorescein (and blue LED light), 99mTc-Sulfur-colloid (and gamma probe) and MBD. Inj Fluorescein 4% was injected, 1 ml each peri-tumoral and sub-areolar five minutes before axillary incision. Axillary dissection was performed irrespective of SLNB histology. The SLN-IR and FNR with various tracers and their combinations were compared. RESULTS: The mean number of SLNs identified was 3.5 ± 1.8 (range 1-6). The SLN-IR using RP alone was 94%, fluorescein alone was 92%, and MBD alone was 82%. The SLN-IR using fluorescein plus MBD combination was 95.4%, compared to 97% using MBD plus RP combination. FNR was 6.3% using fluorescein plus MBD, as well as RP plus MBD combinations. CONCLUSIONS: SLN-IR of > 90% and SLN-FNR of < 10% using fluorescein plus MBD combination are in acceptable range, and are comparable to that of RP plus MBD combination. Fluorescein can replace RP for performing SLNB, in combination with MBD.

Extracervical endoscopic thyroid surgery via Bilateral Axillo-Breast approach (BABA).

Extracervical, scarless in-the-neck endoscopic thyroidectomy (SET) is a relatively new offshoot of minimal access neck surgery which is gaining popularity rapidly. Among all the approaches described, hybrid approaches such as axillary-breast and bilateral axillo-breast (BABA) are most practiced world over. We have performed more than 130 cases of SET using various approaches (ABA, BABA and transoral vestibular approach). We find BABA most suitable for patients who present with larger goitres (≥6cm), toxic glands or low-grade thyroid cancers and are desirous of SET. Here, we describe the surgical technique of BABA, its pros and pitfalls based on our experience.

Poorly differentiated thyroid carcinoma and poorly differentiated area in differentiated thyroid carcinoma: is there any difference?

PURPOSE: Poorly differentiated thyroid carcinoma (PDTC) patients have worse outcomes than patients with differentiated thyroid carcinoma (DTC), but the implication of poorly differentiated areas (PDAs) noted in DTC is not very well understood. The aim of the present study was to compare the clinicopathologic profiles and outcomes of PDTC and DTC with PDA. METHODS: A total of 142 patients, managed at out center between September 1989 and June 2016, were enrolled in this retrospective study. Histology was reviewed, and the patients were divided in the following three groups: poorly differentiated carcinoma [PDTC; group 1 (n = 27)]; papillary thyroid carcinoma with PDA [PTC with PDA; group 2 (n = 27)]; and follicular thyroid carcinoma with PDA [FTC with PDA; group 3 (n = 88)]. Clinico-pathologic profiles and outcomes were compared between the three groups. The Kaplan-Meier method was used for survival analysis. The log-rank test and Cox regression model were used to perform univariate and multivariate analyses of the factors affecting the overall survival (OS). RESULTS: The clinical profiles of the three groups were comparable except for significantly less incidence of lymph node involvement (p = 0.002) and extra-thyroidal invasion (p = 0.002) and higher incidence of distant metastases (p = 0.01) in group 3. Median follow-up period was 47.5 months, and 5- and 10-year OS were 57 and 14%, respectively. There was no difference between OS of PDTC and DTC (group 2 + 3), but group 3 patients had significantly better OS than group 2 patients. Univariate analysis revealed that tumor size (p = 0.04), extra-thyroidal invasion (p = 0.05), lateral compartment lymphadenopathy (p = 0.002), distant metastases (p = < 0.001), absence of encapsulation (p = 0.03), and > 75% PDA (p = 0.001) were associated with worse OS. Multivariate analysis revealed tumor size (p = 0.005), distant metastases (p = 0.012), lymphadenopathy (p = 0.017), TNM staging (p = < 0.001), and PDA > 75% (p = < 0.001) to be significantly associated with OS. CONCLUSION: There is no difference in the outcomes of PDTC and DTC with PDA. However, PTC patients with PDA have worse outcomes than FTC patients with PDA. Irrespective of tumor type, the presence of more than 75% PDA in DTC is associated with adverse outcomes.

Outbreaks of dengue in Central India in 2016: Clinical, laboratory & epidemiological study.

Background & objectives: Dengue virus (DENV) causes outbreaks and sporadic cases in tropical and subtropical countries. Documenting intricacies of DEN outbreaks is important for future interventions. The objective of this study was to report clinical, laboratory and epidemiological features of DEN outbreaks reported in different districts of Central India in 2016. Methods: In 2016, outbreaks (n=4) suspected of DEN were investigated by rapid response team. Door-to-door fever and entomological surveys were conducted. Blood samples were collected and tested using NS1 or IgM ELISA; real-time reverse transcription-polymerase chain reaction was done to identify serotypes of DEN virus (DENV). NS1-positive samples were tested for the presence of IgG by ELISA. Clinical and demographic data were collected and analyzed. Results: Outbreaks occurred in both urban and rural areas in monsoon season and Aedes aegypti was identified as the vector. Fever, chills, headache and myalgia were the major symptoms; no fatality was recorded. Of the 268 DEN suspects, 135 (50.4%) were found serologically positive. DEN positivity was higher (n=75; 55.56%) among males and in the age group of 16-45 yr (n=78; 57.8%). DENV 3 followed by DENV 2 were detected as the major responsible serotypes. High attack rates (up to 38/1000) and low cumulative IgG prevalence (14.9%) were recorded in rural areas. Interpretation & conclusions: Our study showed that DENV 3 was the major serotype responsible for outbreaks that occurred in monsoon. High attack rates and lower number of secondary infections in rural areas indicated that DENV is emerging in rural parts of Central India. Early diagnosis at local level and timely intervention by mosquito control activities are needed to avoid such outbreaks in future.

Novel 1,4-benzothazines obliterate COX-2 mediated JAK-2/STAT-3 signals with potential regulation of oxidative and metabolic stress during colorectal cancer.

1,4-benzothiazines have ameliorative effects through inhibition of COX-2 mediated STAT-3 pathways at G-protein couple receptor site. As per this scenario, we recently prepared and tested novel 1,4-benzothiazine derivatives against HT-29 human colon cancer cell line. Two compounds namely AR13 and AR15 showed higher inhibitions among all the synthesized compounds. In the present context, we conducted the in vivo antiproliferative action and identified the molecular mechanism associated to cytotoxic action of AR13 and AR15 in dimethylhydrazine (DMH) induced colorectal carcinoma (CRC) model. Various physiological, oxidative stress, histopathology, ELISA, qRT-PCR, western blot and NMR-based metabolomics were accomplished to evaluate the anticancer effect of titled compounds. Both compounds were subjected to histological and biochemical tests to observe the protective action of the compounds. ELISA showed potential role of these compounds to normalize increased levels of IL-2, IL-6 and COX-2 mediators. This action was more pronounced for COX-2 rather than IL-2 and IL-6. Gene expression analyses further revealed that both of them attenuated the over-expressed COX-2 gene. Furthermore, it was confirmed that these compounds exerted antitumor potential via preventing COX-2 induced JAK-2 and STAT-3 phosphorylation. This action was substansiated by immunohistochemistry using JAK2, p-JAK2, STAT3 and p-STAT3 targets in colon tissue. Finally, score plots of PLS-DA models exhibited significant metabolic discriminations between the treated and CRC groups, and both compounds showed ability to restore the imbalance of multiple metabolites during CRC. In conclusion, our study provided the evidence towards better antiproliferative effect of AR13 and AR15 in DMH-induced CRC through the blockade of COX-2/JAK-2/STAT-3 signal transduction pathway and could be demonstrated as useful anti-CRC candidate molecules for future anticancer therapy.

Changing Profile of Primary Hyperparathyroidism Over Two and Half Decades: A Study in Tertiary Referral Center of North India.

BACKGROUND: Most of the cases of PHPT in developing countries present in symptomatic stage, some even in very advanced stage but in recent years the trend seems to be changing. This has been corroborated from few recently published literature from developing countries. The scope of this study is to further carry out an in-depth analysis of various clinical and biochemical parameters of PHPT patients at a tertiary care center of northern India. METHODS: In this retrospective analysis, a total of 333 patients with PHPT from the year 1990 to 2016 were studied. The study population was divided into three subgroups based on the time span; 1990-1999 (n = 34), 2000-2009 (n = 112), 2010-2016 (n = 187), and clinical and biochemical parameters were compared. RESULTS: The clinical presentation has evolved progressively with increase in older age group (35 vs 39 vs 43.85, p < 0.001), less patients with musculoskeletal symptoms (85.3 vs 76.8 vs 61%, p = 0.002) and less patients with severe bone disease (29.4 vs 10.7 vs 10.7%, p = 0.088). Biochemical parameters also showed a changing trend with significant decrease in mean S. Alkaline phosphatase (1393 vs 965 vs 414.8 IU/L, p < 0.001) and S. iPTH (837.52 vs 812.89 vs 635.74 pg/mL, p = 0.02). Vitamin D nutrition status is still suboptimal but shows improvement, and more patients are insufficient as compared to previous deficient state (mean S. Vitamin D-10.31 vs 16.16 vs 25.30 ng/mL, p < 0.001). CONCLUSIONS: Our study reveals a change in trend in PHPT which is similar to evolution of this disease in western population and positively corroborated with observations from China, Hong Kong and Turkey.