Gaurav Agarwal

Is Total Thyroidectomy the Surgical Procedure of Choice for Benign Multinodular Goiter? An Evidence-Based Review

BackgroundBenign multinodular goiter is one of the most common endocrine surgical problems. The appropriate surgical procedure for its effective and safe management is a matter of debate. Though seen by some as an overly hazardous procedure because of the risk of recurrent laryngeal nerve injury and damage to parathyroid function, total thyroidectomy has replaced subtotal thyroidectomy as the procedure of choice, as the latter is associated with significant recurrences.MethodsA systemic literature review was undertaken of all available medical literature to evaluate whether total thyroidectomy is the appropriate, safe and effective surgical procedure for benign multinodular goiter.ResultsThere is consistent level II–IV evidence that subtotal thyroidectomy results in recurrence in up to 50% patients. Incidental thyroid cancers are detected in 3%–16.6% of apparently benign goiters in numerous studies, mostly providing level IV evidence, one third of which would need further surgical treatment after subtotal thyroidectomy. Studies comparing subtotal thyroidectomy and total thyroidectomy, including two each of prospective randomized and prospective nonrandomized ones, provide level II–IV evidence that permanent complication rates associated with subtotal thyroidectomy and total thyroidectomy are not different, although the rate of transient hypocalcemia is higher with total thyroidectomy. On basis of these findings, a grade B recommendation can be made that subtotal thyroidectomy is associated with significant recurrence of goiter, leaves a small number of incidentally detected thyroid cancers inadequately treated, and provides little significant safety advantage over total thyroidectomy. Grade C recommendations can also be made about total thyroidectomy being a safe and effective procedure for benign multinodular goiters in the hands of expert surgeons, based on the extensive level IV evidence, and limited level II and level III evidence, which show that the risk of permanent vocal cord palsy and hypoparathyroidism associated with total thyroidectomy is below the acceptable 2% rate, but not without exceptions.ConclusionTotal thyroidectomy is the procedure of choice for the surgical management of benign multinodular goiter.

Total thyroidectomy is now the preferred option for the surgical management of Graves’ disease

Purpose:  Subtotal thyroidectomy has been advocated as the standard treatment for Graves’ disease because of the possibility of avoiding thyroxine therapy as well as the assumed lower risk of complications compared to total thyroidectomy. However, the long‐term results of subtotal thyroidectomy are not as good as they were previously believed to be, as evidenced by the increasing incidence of hypothyroidism. If the risk of complications from total thyroidectomy is no higher, then that procedure offers significant advantages in the surgical management of Graves’ disease. The aim of this study therefore was to compare the complication rate of the two procedures in patients with Graves’ disease.

Breast Cancer Care in Developing Countries

BackgroundBreast cancer is the commonest cancer of women the world over, and its incidence is rising, especially in developing countries, where the disease poses a major health care challenge. This growing incidence in developing countries reflects the advanced stage at diagnosis, low levels of public awareness of the risk for the disease, and poor medical infrastructure and expertise, with the resultant poor treatment outcomes.MethodsThis article provides a collective edited summary of the presentations at the symposium titled “Breast Cancer Care in Developing Countries,” held as part of the Breast Surgery International program at the International Surgical week 2007, Montreal, Canada, August 2007. The aim of the presentations was to bring out the diverse clinical pathological and outcomes-related facts of breast cancer care available to women in several countries. As the incidence of breast cancer continues to rise steadily in the developing world, the lack of awareness of this disease and the absence of breast cancer screening programs make it almost certain that the majority of breast cancers are diagnosed at an advanced stage. In addition, the quality of care available for breast cancer patients varies widely according to where the patient is treated.ResultsThough there are some centers of excellence providing multimodality protocol-based treatment on a par with the best anywhere in the world, most breast cancer patients receive inadequate and inappropriate treatment because of a lack of high-quality infrastructure—and sometimes skills—and, above all, because of limited financial resources.ConclusionsIn countries where these limitations are present, there is a need to emphasize public health education, promoting early diagnosis. In addition, resources must be directed toward the creation of more public facilities for cancer treatment. As these goals are met, it is likely that there will be a much-needed improvement in breast cancer care in developing countries.

Minimally invasive parathyroidectomy using the 'focused' lateral approach. II. Surgical technique.

Background: This paper describes the technique of minimally invasive parathyroidectomy. The technique is based on a thorough understanding of the anatomy of the fascial planes in neck, the surgical pathology and embryology of parathyroid glands and precise anatomical interpretation of preoperative localization studies.

Minimally invasive parathyroidectomy using the ‘focused’ lateral approach. I. Results of the first 100 consecutive cases

Background: A feasibility study of ‘focused’ minimally invasive parathyroidectomy (MIP) using a lateral approach was commenced in 1999. The aim of the present paper was to evaluate the effectiveness and safety of this procedure in the first 100 consecutive patients.

Functional expression of sodium iodide symporter (NIS) in human breast cancer tissue.

Sodium iodide symporter (NIS) is a molecule involved in active accumulation of iodine in thyroid gland for the biosynthesis of thyroid hormone. Its expression has also been demonstrated in extra-thyroidal tissues including lactating mice mammary gland and also in human breast cancers. Iodide transport in thyroid cells through NIS is the basis for using radioiodine for diagnosis and treatment of differentiated thyroid carcinoma. The similar approach may prove beneficial for the diagnosis and treatment of breast cancer if iodine uptake, its retention and NIS expression can be shown unequivocally in malignant tumors. The aim of the present study was to investigate NIS expression, in vivo iodine transport ability and fate of iodine in human breast tumors. Women (age 33–58 years) with infiltrating duct carcinoma confirmed by FNAC and subsequent histopathology were the subject of this study. Expression of NIS RNA and protein was confirmed by RNAase protection assay, western blot and immunohistochemistry respectively in surgically excised breast tumor tissue. Iodine transport ability and its nature was assessed both in vivo and in vitro. We report high NIS expression at both transcriptional and translational level and its ability to transport iodine in human breast tumors. The in vivo iodine transport ability was confirmed by scintigraphy. Unlike thyroid, perchlorate and thiocyanate do not inhibit iodine transport in breast tumors. The presence of iodinated proteins suggests the longer retention time. The unequivocal demonstration of NIS expression, its functionality and retention of iodine by organification further provides supportive evidence for use of radioiodine as an additional treatment modality of human breast carcinoma.

Cardiovascular dysfunction and catecholamine cardiomyopathy in pheochromocytoma patients and their reversal following surgical cure: results of a prospective case-control study.

BACKGROUND Cardiovascular (CV) dysfunction and cardiomyopathy can cause perioperative morbidity in pheochromocytoma patients, but have not been studied systematically. This prospective, case-control study evaluated nature and extent of CV dysfunctions and their reversal following curative pheochromocytoma surgery. METHODS Thirty-five pheochromocytoma patients, 9 normotensive nonpheochromocytoma adrenal tumors and 10 essential hypertensives were evaluated with 2-dimensional echocardiography, tissue Doppler, and serum N-terminal pro-brain natriuretic peptide (s-NTpro-BNP, a sensitive myocardial damage biomarker) serially before and after treatment. RESULTS Pheochromocytoma patients had systolic and diastolic dysfunction, reduced left ventricular (LV) ejection fraction (EF), increased LV end-diastolic and systolic dimensions and volumes, myocardial performance index, and decreased transmitral early/late velocity ratio, which were worse compared with controls. All indices improved significantly with α-blockade and after pheochromocytoma resection, and normalized over 3-6 months. Tissue Doppler early velocity was lower (P = .04) and s-NT-proBNP higher (P = .0001) in pheochromocytoma patients compared with controls. Seven pheochromocytoma patients (20%) had significant LV dysfunction (LVEF <45%; s-NTpro-BNP levels >500 pg/mL) and had more marked postoperative improvement. CONCLUSION Global LV diastolic and systolic dysfunctions specific to pheochromocytoma are common and improve early postoperatively, with sustained improvement upon follow-up. Detailed cardiac evaluation with echocardiography, tissue Doppler, and s-NTpro-BNP may help to reduce perioperative morbidity and monitor recovery in pheochromocytoma patients.

Metastatic Differentiated Thyroid Carcinoma: Clinicopathological Profile and Outcome in an Iodine Deficient Area

Reports on metastatic differentiated carcinoma in endemic goiter regions are scarce. The aim of this study was to look into the clinicopathological profile and outcome of patients with metastatic differentiated thyroid carcinoma (DTC) of endemic origin. This was a retrospective study of 28 cases of metastatic DTC out of a total of 140 DTC patients managed between 1990 and June 1999. Demographic data, clinicopathological profile, operative and radioiodine ablation therapy details, and follow-up findings were noted. The overall incidence of distant metastases in our series was 20%. Mean age was 48.5 +/- 12.8 years (32.1%patients were < 45 years). Most metastases were detected synchronously (85.7%) and were multiple, with the skeletal system being the commonly affected site. Out of 22 cases having skeletal metastases, 6 patients were young (< 45 years). Though most patients with skeletal metastases had follicular carcinoma (FTC), 4 cases had papillary thyroid cancer (PTC). Near total or total thyroidectomy was done in 26 cases. Sixteen patients required regional lymph node dissection. Resection of metastases was performed in 9 cases. Histopathological diagnosis was PTC, FTC, and poorly differentiated carcinoma in 32.1%, 50.0%, and 17.9% of cases, respectively. Most patients had good symptomatic palliation following administration of I131 therapy. In 17.9% of cases there were locoregional recurrences. There was an overall 28.6% mortality. Two patients expired in the perioperative period. Six others died in follow-up (all within 3-9 months). In contrast to iodine sufficient regions, the incidence of metastases was high; the majority of cases had synchronous, symptomatic skeletal metastases. Skeletal metastases were not infrequent even in cases of PTC and in young patients. One-third of the cases were young. Though survival was poor despite aggressive management, significant symptomatic palliation could be achieved in most cases.

Inhibition of autophagy stimulate molecular iodine-induced apoptosis in hormone independent breast tumors

Estrogen receptor negative (ER(-ve)) and p53 mutant breast tumors are highly aggressive and have fewer treatment options. Previously, we showed that molecular Iodine (I(2)) induces apoptosis in hormone responsive MCF-7 breast cancer cells, and non-apoptotic cell death in ER(-ve)-p53 mutant MDA-MB231 cells (Shrivastava, 2006). Here we show that I(2) (3 μM) treatment enhanced the features of autophagy in MDA-MB231 cells. Since autophagy is a cell survival response to most anti-cancer therapies, we used both in vitro and in vivo systems to determine whether ER(-ve) mammary tumors could be sensitized to I(2)-induced apoptosis by inhibiting autophagy. Autophagy inhibition with chloroquine (CQ) and inhibitors for PI3K (3MA, LY294002) and H+/ATPase (baflomycin) resulted in enhanced cell death in I(2) treated MDA-MB231 cells. Further, CQ (20 μM) in combination with I(2), showed apoptotic features such as increased sub-G1 fraction (∼5-fold), expression of cleaved caspase-9 and -3 compared to I(2) treatment alone. Flowcytometry of I(2) and CQ co-treated cells revealed increase in mitochondrial membrane permeability (p<0.01) and translocation of cathepsin D activity to cytosol relative to I(2) treatment. For in vivo studies ICRC mice were transplanted subcutaneously with MMTV-induced mammary tumors. A significant reduction in tumor volumes, as measured by MRI, was found in I(2) and CQ co-treated mice relative to I(2) or vehicle treated mice. These data indicate that inhibition of autophagy renders ER(-ve) breast tumor cells more sensitive to I(2) induced apoptosis. Thus, I(2) together with autophagy inhibitor could have a potential tumorostatic role in ER(-ve) aggressive breast tumors that may be evaluated in future studies.

Cardiovascular dysfunction in symptomatic primary hyperparathyroidism and its reversal after curative parathyroidectomy: Results of a prospective case control study

BACKGROUND Cardiovascular mortality in primary hyperparathyroidism (PHPT) is attributed to myocardial and endothelial dysfunction. In this prospective, case-control study we assessed cardiovascular dysfunction in patients with symptomatic PHPT and its reversal after successful parathyroidectomy. METHODS Fifty-six patients with symptomatic PHPT underwent two-dimensional echocardiography, tissue Doppler (diastolic function assessment), serum N-terminal pro-brain natriuretic peptide (s-NTproBNP, a myocardial damage marker), and endothelial- and smooth muscle-dependent vasodilatory response (vascular dysfunction) studies before, 3, and 6 months after parathyroidectomy; 25 age-matched controls were studied similarly. RESULTS Patients had greater left ventricular mass (192 ± 70 vs. 149 ± 44 g; P = .006), interventricular septal thickness (10.8 ± 2.5 vs. 9.0 ± 1.6 mm; P = .001), posterior wall thickness (9.9 ± 2.0 vs. 8.6 ± 2.2 mm; P = .004), and diastolic dysfunction (lower E/A trans-mitral flow velocity ratio [1.0 ± 0.4 vs. 1.3 ± 0.4; P = .01). Patients had greater s-NTproBNP (4,625 ± 1,130 vs. 58 ± 49 pg/mL; P = .002) and lower endothelial-mediated vasodilation (9.3 ± 8.6 vs. 11.7 ± 6.3%; P = .03) and smooth muscle-mediated vasodilation (20.1 ± 17.9 vs. 23.8 ± 11.2%; P = .01). Improvements in left ventricular mass, systolic and diastolic function, and smooth muscle-mediated vasodilation were noted from 3 to 6 months after parathyroidectomy. Endothelial-mediated vasodilation did not improve significantly. S-NTproBNP levels mirrored echocardiographic changes with a substantial, sustained decrease. Results were similar in hypertensive and normotensive patients. CONCLUSION Symptomatic PHPT patients have substantial cardiac and vascular dysfunction, which improve by 6 months after parathyroidectomy. Objective cardiovascular evaluation may improve outcomes in symptomatic PHPT patients.