Kul Ranjan Singh

Papillary Thyroid Cancer and Hashimoto's Thyroiditis: An Association Less Understood.

Hashimoto’s thyroiditis (HT), part of the spectrum of autoimmune thyroid diseases is a major cause of thyroid hypofunction worldwide. Papillary thyroid carcinoma (PTC), the most prevalent of all thyroid carcinomas has been associated with HT. Literature on this association are based on preoperative FNA or post thyroidectomy histopathology reports, which are subject to potential biases. Molecular, hormonal and histopathalogical basis of this association has been hypothesized, however a definite causal association has not been proved till date. This review aims to study the basis of this association and clinical features and management of HT concurrent with PTC. There are no distinctive clinical or radiological features that categorically differentiates HT concurrent with PTC from PTC or which can pick up a nodule harboring PTC in setting of HT. Smaller nodule size and radiological features like hypoechogenecity; hyper vascularity and calcification in a clinical setting of hypothyroidism have a higher odds ratio for malignancy and merit further investigations. PTC associated with HT has been seen to be less aggressive with earlier presentation with lesser chances of extra thyroidal extension and lymph nodal metastasis. The management and follow up of PTC in HT is no different from that of PTC alone. The prognosis of PTC concurrent with HT is better compared to age and stage matched PTC in terms of lower recurrence and disease free and overall survival.

Letter to the Editor: A Prospective Comparative Study on Improvement of Hyperthyroid Cardiovascular Dysfunction in Patients Undergoing Total Thyroidectomy Versus Medical Management

We read the article ‘‘A Prospective Comparative Study on Improvement of Hyperthyroid Cardiovascular Dysfunction in Patients Undergoing Total Thyroidectomy Versus Medical Management’’ [1] with great interest. We congratulate the authors for their study as it deals with a very pertinent issue faced by all endocrine surgeons. However, we have queries which we would like to put forward. All patients recruited in the study were given antithyroid drugs to render them euthyroid. What was the duration of this treatment and what were the criteria followed to declare a patient euthyroid? The ATA guidelines recommend a minimum of 12–18 weeks of antithyroid drugs as the optimum period for patients who choose medical management [2]. Were the non-surgical group of this study managed in accordance with this? Although surgery is the treatment of choice for patients with toxic multinodular goitre, Radioactive Iodine Ablation (RAIA) is an accepted treatment modality for Graves’ disease. Were the patients with Graves’ disease educated about it and given the option of RAIA [2]? As discussed in the paper, patients with diagnosed/known cardiac co-morbidities were left out of the study. How did the authors differentiate cardiac morbidity from hyperthyroidism from that because of co-existing, previously undiagnosed cardiac ailment, especially in older patients? This may be a source of bias, as treatment of cardiac condition with appropriate medications would have resulted in clinical improvement, which then was attributed to surgery. NT pro-BNP is a marker of cardiac morbidity, whose levels are elevated in a variety of conditions, including hyperthyroidism [3]. It is a good marker of systolic dysfunction, which is confounded by a lot of other factors and can be elevated in the absence of cardiac morbidity as well [4] (viz. old age, chronic renal failure), hence cannot be considered absolute marker of reversal of cardiac morbidity in post-thyroidectomy patients. Lastly, the normal reference ranges for cardiac parameters under consideration in this study are given in Table 1, while those observed in patients are mentioned in Table 2 [1]. Many of the parameters recorded at admission fall within the normal range, as evident in Table 2. How did the authors draw conclusion regarding improvement after surgery considering the fact that these parameters were normal or near normal?

P-Glycoprotein Expression in Indian Breast Cancer Patients with Reference to Molecular Subtypes and Response to Anthracycline-Based Chemotherapy—a Prospective Clinical Study from a Developing Country

Chemo-resistance is an important factor determining the response of tumor to neoadjuvant chemotherapy (NACT). Our study was aimed to determine the role of P-glycoprotein (P-glyp) expression as a predictor of response to NACT in locally advanced breast cancer (LABC) patients with special reference to molecular subtypes. Sixty cases of locally advanced breast cancer (LABC) were subjected to trucut biopsy and the tissue samples were evaluated immunohistochemically for P-glyp, ER, PR, and Her 2 neu status. Pre- and post-NACT P-glyp expression was correlated with clinical response (using WHO criteria after three cycles of CEF regimen) and molecular subtypes. The change in the P-glyp expression before (pre-) and after (post-) NACT was statistically significant with higher stage (p = 0.02), hormonal negative molecular subtypes (p = 0.01), and poor clinical response (p = 0.01). Pre-NACT-positive P-glyp expression is associated with higher stage and hormonal negative molecular subtypes and poor clinical response. The increased expression of P-glyp induced by NACT likely explains the concept of acquired chemo-resistance and may prove as an intermediate checkpoint in determining chemo-sensitivity for further treatment so that additional doses of ineffective chemotherapy may be avoided in non-responders translating into better patient safety.

A Survey on Breast Cancer Awareness Among Medical, Paramedical, and General Population in North India Using Self-Designed Questionnaire: a Prospective Study

Breast cancer (BC) has become the most common cancer in urban women. Unfortunately, most women are not aware of BC symptoms/signs, prevention, and management. In resource-limited countries like India where we do not have structured screening/awareness programs, a majority of women present with locally advanced BC. The aim of our study is to identify the present status of awareness about BC prevention, early detection, symptoms, and management in urban and rural Indian women (medical, paramedical, and nonmedical) and to assess whether education and socioeconomic strata have any role in better awareness about BC or not. We did a prospective cross-sectional observation study among the medical, paramedical, and nonmedical women in the northern part of India. We designed a questionnaire keeping in mind the three domains about BC—knowledge (questions 1–25 include risk factors, genetics, lifestyle changes, hormones, associated cancers, and modes of presentation like lump, nipple/skin changes), breast self-examination (questions 25–37), and attitude to prevention and early detection (questions 38–44). We also asked how many do breast self-examination (BSE) and what they think are the three main factors responsible for late presentation and the three main ways to increase BC awareness. The Likert scale was used for objective assessment. We analyzed the whole data using SPSS software version 15. A total of 220 women out of 270 completed the questionnaire. Out of 220 women, 26.4% were medical, 20.9% paramedical, and 52.7% nonmedical. Most women were educated (82.7%) and married (65%). 59.5% women resided in urban areas and the rest (40.5%) were from rural areas. We found that there was relatively more knowledge in the medical group; however, the skills of BSE and attitude to prevention and early detection in all the three subgroups and among rural and urban women were suboptimal and not different significantly. The three main factors responsible for delayed presentation were shyness and not knowing BSE, ignorance about BC symptoms, and social stigma of cancer along with financial constraints. The three main ways to improve BC awareness suggested were to have more advertisements on television and social media, roadside campaigns and in colleges along with group discussions and debates, and at grassroots level to involve Anganwadi workers and nurses to create more awareness in villages. There was less breast cancer knowledge and awareness among the nonmedical women compared to those among the medical and paramedical, the skills of BSE and attitude to prevention and early detection were suboptimal in all the three groups. Rural or urban dwellings did not make much difference in BC knowledge, skills of BSE, and attitude to prevention. More awareness regarding breast cancer symptoms with early detection and BSE need to be addressed with more information dissemination via social media, campaigns, and involvement of paramedics and social workers.

Expression of vitamin D receptor and vitamin D status in patients with oral neoplasms and effect of vitamin D supplementation on quality of life in advanced cancer treatment

Aim of the study Vitamin D receptor (VDR) expression and serum vitamin D scores in oral premalignant lesions and oral cancer have not been widely analyzed. The role of vitamin D supplementation in advanced oral cancer for improving quality of life (QOL) is also a matter of research. Material and methods Vitamin D receptor expression and vitamin D scores were analyzed in normal oral mucosa (n = 95), leukoplakia (n = 23) and oral cancer (n = 87). 45 patients with advanced oral cancer subjected to chemoradiation were evaluated for the effect of vitamin D supplementation on most observable QOL parameters such as oral mucositis, swallowing performance and overall QOL. Results Vitamin D receptor expression was increased in oral neoplastic lesions. Vitamin D scores were significantly lower in cases compared to healthy controls (p = 0.002). Vitamin D supplementation significantly reduced the therapy-related toxicities in advanced cancer, thus reducing morbidity and improving QOL. Conclusions Vitamin D receptor expression is increased in premalignant lesions and oral cancer. Vitamin D insufficiency and deficiency are prevalent in patients with oral neoplastic lesions. Vitamin D supplementation has a role in reducing treatment-related toxicities, especially in advanced cancer.

Adrenal Teratoma: Unusual Tumor with Typical Imaging Characteristics

Teratomas per se are rare and retroperitoneal teratomas are a still rarer entity. We report the image of a patient who presented with a large adrenal teratoma which was nonfunctional biochemically and who underwent surgical excision. The imaging characteristics are suggestive of teratoma and must be kept in mind while managing large adrenal tumors.

Surgical Techniques for Dealing with Intraluminal Thrombus of Great Vessels in Advanced Differentiated Thyroid Carcinoma

Aim: We aim to define and refine the surgical technique for dealing with intraluminal thrombus of great vessels in advanced differentiated thyroid carcinoma (DTC) to reduce the morbidity. Background: Venous tumor thrombus from DTC is a rare occurrence with sequelae that cause increased morbidity and early mortality. Management of such patients poses a challenge to surgeons. Materials and methods: We define the surgical planning and road map for surgical management of advanced DTC with tumor thrombus involving the internal jugular vein (IJV) and superior vena cava (SVC) by sacrificing one IJV and retrieving the thrombus from the SVC by Fogarty catheter. This technique has minimal morbidity with good outcome. Conclusion: By appropriate planning and meticulous surgical techniques, we can aggressively manage patients of advanced DTC with venous tumor thrombus and reduce the morbidity. Clinical significance: By surgical techniques leading to complete surgical resections and saving native vital structures, we can aim for successful aggressive surgical management of advanced DTC with venous tumor thrombus.

Androgen Receptor Expression in an Indian Breast Cancer Cohort with Relation to Molecular Subtypes and Response to Neoadjuvant Chemotherapy - a Prospective Clinical Study

Background: Breast cancer (BC) is associated with advanced presentation in developing countries like India due to various socio-economic factors. The presence of BC molecular subtypes such as the triple-negative (TN) subtype adds to this menace. Androgen receptor (AR) is emerging as a new biological marker. The aim of this study was to examine the prevalence of AR with relation to different BC subtypes, and its role in predicting response to neoadjuvant chemotherapy. Methods: 116 cases of invasive BC (infiltrating ductal carcinoma, not otherwise specified) were evaluated. AR expression was correlated with clinicopathological factors, established prognostic markers, BC subtypes and it ability for predicting response to neoadjuvant chemotherapy. Results: AR was expressed in 56% of the cases. AR expression was significantly associated with early stage (p < 0.03), low axillary burden (p < 0.04), estrogen receptor (p = 0.002), progesterone receptor (p = 0.001) expression and luminal A molecular subtype. No significant association was observed with age, tumor size and HER2/neu status. One-third of TNBC cases expressed AR. Higher AR expression corelated to good clinical response to neoadjuvant chemotherapy. Conclusion: AR can be utilized as a predictor of response to neoadjuvant chemotherapy especially in developing countries such as India where the load of advanced disease is high.

Surgical Techniques for operating on Large Adherent Cervical Nodal Metastases from Thyroid Cancer causing Severe Neck Pain and Compression Effects and encasing Major Vessels

Aim: We aim to refine and define surgical techniques for doing difficult adherent bulky cervical nodal metastases from thyroid cancer to help surgeons do dissections with better curability and lesser morbidity. Background: Patients with thyroid cancer with large nodal metastases presenting with severe neck pain due to compression effects and encasing carotid artery and other major vessels pose a challenge to surgeons to do complete resections while preserving important structures in the neck. Materials and methods: We define surgical planning and road map to dissect difficult bulky adherent cervical nodes encasing carotid artery and jugular vein by splaying the plane over carotid sheath by doing adventitial level dissection and dissecting medial and lateral to carotid sheath the large nodal mass adherent to adjacent structures preserving the major vessels and nerve plexus. Conclusion: By appropriate surgical planning and meticulous dissection techniques, we can do major neck dissections with complete resections and same time preserving important structures in the neck minimizing morbidity. Clinical significance: By doing neck dissections with complete oncological resections and saving vital structures in the neck, we aim to offer best possible chance of cure to the patient along with reduced morbidity at same time.

Day Case Thyroid and Parathyroid Surgery: Time to Replicate Same in Developing Countries.

We would like to congratulate the authors for making the concept of same day-discharge in thyroid and parathyroid surgery a seemingly attainable goal [1]. This is more appealing in a developing country like India considering the high incidence of disease and limited patient to bed ratio. In this attempt; however, the patient’s safety should not be in advertently compromised, a few issues need to be clarified before we can replicate a similar practice here. The large number of patients (n = 2,102) analyzed over a decade happens to be a major strength of this study. However, the retrospective nature of the database and the fact that the surgeries were performed by two consultant surgeons and a surgical trainee/ fellow is likely to impact the robustness of inferences from this study. The likelihood of post-operative complications has been related to volume of both the hospital and the surgeon [2]. We concur with the authors that a safe day case surgery begins with proper patient selection; however, the author have not made it clear as to which were the patients personaland home-related circumstances that rendered one suitable for day case surgery. With respect to procedures which can be offered as a day case procedure, it is not clear if the authors offered day case surgery to all patients listed in the less suitable or contra indicated group. More over there remains a continuing controversy between definitions of goiter in terms of size, more so as to what is the threshold for large goiters [3]. The authors have not mentioned the break up of procedure performed for the nodular goiters and follicular adenoma in terms of hemi/total thyroidectomy and the differences between the characteristics of patients between the three groups (day case, ambulatory, and in patients) in patients of various pathologies of thyroid and parathyroid. Also the authors have not made clear, the breakup of complications in terms of the underlying thyroid pathology or procedure that was performed. Both these information would be needed to come to any definite conclusion regarding safety and widespread replication of day case surgery. The practice of administering prophylactic calcium adopted by the unit has proven to be safe and cost-effective in preventing post-operative hypocalcemia after total or completion thyroidectomy [4]. However, the advent of rapid PTH measurement has made prediction of hypocalcemia post-thyroidectomy possible with acceptable accuracy. It has also proven to be cost-effective [5]. Nomo grams predicting post-operative hypocalcemia can avoid unnecessary calcium supplementation which occasionally poses as a risk to patients.