M. J. Paul

Mapping the compound muscle action potentials of cricothyroid muscle using electromyography in thyroid operations: a novel method to clinically type the external branch of the superior laryngeal nerve.

Objective:Variations of the external branch of the superior laryngeal nerve (EBSLN) are well represented in literature but with conflicting reports about the types and variations. Using EMG, the cricothyroid compound muscle action potential (CMAP) was recorded, to identify the EBSLN and classified them according to clinical variation during routine thyroid operations. Summary Background Data:There is increasing awareness among patients and physicians of the consequences of injury to the external laryngeal nerve in thyroid surgeries. There are at least 4 types, which are described in the literature.1 The gold standard of nerve identification is EMG, which we used during operations in this study to identify all the EBSLN by demonstrating CMAP and reclassify them. Based on this principle, to avoid injury during thyroidectomy, we propose a new classification. Methods:This study was a prospective, descriptive study of the EBSLN done during elective thyroidectomy operations. CMAP was demonstrated and EMG was plotted to identify and type them according to clinical variations. The distance between the entry of superior thyroid vessels (STVs) to the lobe and the EBSLN, relationship with the cricothyroid muscle and inferior constrictor muscle were taken into consideration. Based on the possible risk to this during thyroidectomy, we divided them into 4 types. Results:A total of 70 external laryngeal nerves were dissected and confirmed by the CMAPs in 35 total thyroidectomy patients. Using CMAPs, all the nerves were identified. Ia.The nerve can be found within 1 cm from the entry of the vessels into the gland either anterior or intertwined to the STVs or within 3 cm from the cricoid cartilage. Ib.The nerve can be found posterior to the vessels but within 1 cm from the entry of the STV into the gland. This entry point was close to the anterior insertion line of the CT muscle onto cricoid cartilage. II.Nerve can be found within 1 to 3 cm from the entry of the vessels into the gland or within 3 to 5 cm from the cricoid cartilage. III.Nerve can be found between 3 and 5 cm from the entry of the vessels into the gland or more than 5 cm from the cricoid cartilage. Conclusion:New clinical typing of the EBSLN will give a better understanding of the EBSLN in the intraoperative period. EBSLN need not be identified in routine thyroidectomy operations. Even in large goiters, the incidence of nerve at risk does not increase significantly. Injury to EBSLN can be avoided if the principle of ligating the STVs individually away from the CT muscle and close to the capsule of the gland is followed.

Challenges in management of phyllodes tumors of the breast: A retrospective analysis of 150 patients

INTRODUCTION Phyllodes tumors (PT) of the breast seem to get pre-operatively misdiagnosed as fibroadenomas resulting in inadequate resections and high local recurrence rates. MATERIALS AND METHODS Data of 150 patients with PT of the breast managed from January, 2003 to February, 2013 were retrospectively analyzed. Statistical analysis performed using SPSS version 17 (Pearson Chi-square test and analysis of variance test for analysis). AIM The aim of this study is to compare clinico-pathological profile and recurrence rates in patients with benign (B), borderline malignant (BL) and malignant (M) PT. RESULTS In a total of 150 patients with PT (n = 77 B, n = 24 BL, n = 49 M), mean age was 36.92, 44.04 and 40.46 years respectively (P 0.015) and mean tumor size being 8.15 cm, 14.7 cm and 12.9 cm respectively (P 0.000). Pre-operatively cytology suggestive of PT in 24% patients with B PT and 63% in M PT; core tissue biopsy suggestive of PT in 85.4% patients with B PT and 100% in M PT. Recurrence seen in 34.7% out of which 32.7% were post-lumpectomy performed elsewhere. Majority of B PT had lumpectomy (49.3%)/wide local excision (WLE, 31.2%) compared with M PT where 55.1% had simple mastectomy (SM) due to large tumor size. Local recurrence was more in M PT (53%) compared with B PT (20%). We found recurrence rates in L (39.3%) compared with WLE (27.3%) and SM (33.9%) (P 0.049). CONCLUSIONS Larger tumor size, incomplete resection and M/BL histology predicted higher recurrence in PT. Core biopsy is much more accurate than fine needle cytology in the diagnosis.

Causes of discordant or negative ultrasound of parathyroid glands in treatment naïve patients with primary hyperparathyroidism

OBJECTIVES To describe causes of discordant or negative parathyroid ultrasound and to assess factors influencing them. MATERIALS AND METHODS Retrospective review of patients who underwent parathyroidectomy between 2000 and 2012 was done. Imaging findings were compared with operative findings and pathology to identify discrepant (n=60; 32 negative, 28 incorrect) parathyroid ultrasounds. RESULTS Fifty (83.3%) patients had parathyroid adenoma, of which 10 (16.6%) were ectopic and three were double adenomas; 8 (13.3%) had multigland hyperplasia and two had parathyroid carcinoma. Discrepant reports were due to incorrect localisation in 8 (13.3%); difficulty in differentiating thyroid from parathyroid lesion in 12 (20%); large and small size in two and three patients, respectively; overcall in 5 (8.3%) and satisfaction of search in 7 (11.7%) patients. There was significant correlation between presence of multi-nodular goitre and incorrect reports (χ(2)=4.112, p=0.04). Experience of ultrasound operators performing initial and second look ultrasound was significantly different (p<0.0001). Second look ultrasound was concordant with surgical findings in 39(65%) patients; 21 (66%) patients with initially negative ultrasound and four out of five extra-mediastinal ectopic lesions. Ten patients with negative initial ultrasound had elongated parathyroid lesion. Scintigraphy was concordant in 44 (73.3%) patients and nine were ectopic. CONCLUSION Second look ultrasound performed by experienced operator for negative or discordant initial ultrasound of parathyroid is a useful strategy which will improve the accuracy of parathyroid ultrasound. Being able to differentiate thyroid from parathyroid lesion is a factor which will influence performance of parathyroid ultrasound.

Is TIRADS a practical and accurate system for use in daily clinical practice

Aim: To assess the positive predictive value (PPV) and inter-observer agreement of Thyroid Imaging Reporting and Data System (TIRADS) as described by Kwak et al. Materials and Methods: This was a prospective study wherein ultrasound was performed by two radiologists on patients with thyroid nodules >1 cm. The third radiologist interpreted archived images. Ultrasound features and TIRADS category were compared with cytology and surgical histopathology. PPV was calculated for all readers’ combined assessment. Inter-observer agreement was calculated using linear weighted kappa. Results: A total of 238 patients with 272 nodules of mean size 2.9 ± 1.7 cm were included. PPV for malignancy was 6.6%, 32%, 36%, 64%, 59%, and 91% for TIRADS 2, 3, 4a, 4b, 4c, and 5 categories, respectively. Inter-observer agreement was substantial [kappa (k) = 0.61-0.80] for assessment of nodule echogenicity, margins, calcification, and shape and good (k = 0.570, P < 0.001) for assessment of composition of the thyroid nodules. Overall agreement between observers was substantial for assigning TIRADS category [multi-rater weighted kappa coefficient (wt k) = 0.721, P < 0.001]. Conclusions: TIRADS is a simple and practical method of assessing thyroid nodules with high PPV and good inter-observer agreement.

A randomized controlled experimental study comparing chitosan coated polypropylene mesh and Proceed™ mesh for abdominal wall defect closure

Background Abdominal wall defects and hernias are commonly repaired with synthetic or biological materials. Adhesions and recurrences are a common problem. A study was conducted to compare Chitosan coated polypropylene mesh and a polypropylene–polydioxanone composite with oxidized cellulose coating mesh (Proceed™) in repair of abdominal wall defect in a Rabbit hernia model. Methods A randomized controlled experimental study was done on twelve New Zealand white rabbits. A ventral abdominal defect was created in each of the rabbits. The rabbits were divided into two groups. In one group the defect was repaired with Chitosan coated polypropylene mesh and Proceed mesh™ in the other. The rabbits were operated in two phases. They were followed up at four weeks and twelve weeks respectively after which the rabbits were sacrificed. They were evaluated by open exploration and histopathological examination. Their efficacy in reducing adhesion and ability of remodeling and tissue integration were studied. Results There was no statistical significance in the area of adhesion, the force required to remove the adhesions, tissue integration and remodeling between Chitosan and Proceed™ group. Histological analysis revealed that the inflammatory response, fibrosis, material degradation and remodeling were similar in both the groups. There were no hernias, wound infection or dehiscence in any of the studied animals. Conclusion Chitosan coated polypropylene mesh was found to have similar efficacy to Proceed™ mesh. Chitosan coated polypropylene mesh, can act as an anti adhesive barrier when used in the repair of incisional hernias and abdominal wall defects.

Mutational analysis of RET proto-oncogene among patients with medullary thyroid carcinoma and ‘at risk’ carriers from India

Mutations associated with the RET proto-oncogene have been extensively investigated in patients with medullary thyroid carcinoma (MTC) since its first description in 1993. Several germline activating point mutations on exons 10, 11, 13, 14, 15 and 16 of this gene, are known to be associated with multiple endocrine neoplasia type 2 (MEN 2) and familial MTC (FMTC). These mutations are inherited in an autosomal dominant manner necessitating screening of index cases and their families to identify carriers who could benefit from early prophylactic thyroidectomy. In addition to these mutations, several single nucleotide polymorphisms (SNPs) have also been described though it is debatable whether these polymorphisms have either a predisposing or a modifying role in the pathogenesis of MTC. MTC is a malignancy with a good prognosis where patients have reasonable longevity even in the presence of metastases. Our previous experience over a 20-year period has shown that survival rates are favorable even in cases with metastases (43%) at the time of diagnosis. Understanding the mutational profile of MTC in the Indian population is therefore crucial to establishing a diagnosis and performing early prophylactic thyroidectomy before development of disease. However, a detailed report of the mutational profile among Indian patients is lacking. We report RET mutational analysis of the six ‘risk exons’ along with characterization of the four known exonic RET polymorphisms among patients with MTC and among ‘at risk’ carriers. Thirty-six patients with MTC who attended the outpatient clinic between January 2008 to December 2009 were included in the study. The diagnosis of MTC was based on the histopathology of the tumor after thyroidectomy. Peripheral venous blood was collected from all these patients and 11 ‘at risk’ carriers after obtaining consent. Genomic DNA extracted from 200 ll of blood was amplified with primers for exons 10, 11, 13, 14, 15 and 16. PCR products were sequenced using the ABI PRISM 310 genetic analyzer (Applied Biosystems, Foster City, CA, USA). The association between mutational status and various demographic, clinical factors were evaluated by Chi-square test or Fisher’s exact test using stata 10.0 (StataCorp, College Station, TX, USA). The 36 index cases (24 males and 13 females), included cases of MEN IIA (n = 3), MEN IIB (n = 2), FMTC (n = 2) and apparently sporadic MTC (sMTC, n = 29). The mean age of patients included was 47 years (range 19–74 years) and median serum calcitonin was 4650 pg/ml (range 133–97, 8000 pg/ml). Metastases were observed in 72% of patients (n = 26). Mutational analysis showed that 28% (10/36) of patients in this study carried a germline mutation which included all cases of MEN II and FMTCs and three patients (10%; 3/36) who were apparently sporadic cases (Table 1). Mutations at codon 634/exon 11 was most common (n = 5), while two patients had a mutation at codon 618 and one each at codon 804, 891 and 918. Similar sequence analysis was performed for all the 11 ‘at risk’ carriers and six harbored the same mutations as in the index case. Four of them underwent prophylactic thyroidectomy. While the percentage of mutations among the familial and sporadic cases of MTC in this study are comparable to the previous reported studies from other geographic regions of the world, it differs from the only other Indian study which reported a larger number (18/24) of sMTC. Irrespective of these differences, the presence of mutations in sporadic cases and among ‘at risk’ carriers, demonstrates the benefit of routine screening of all patients with MTC and their first degree relatives even in a resource limited setting. Sequences were also analyzed for the four known exonic polymorphisms (G691S/exon 11, L769L/exon 13, S836S/ exon 14 and S904S/exon 15). SNPs at 691 and 769 were more common (47% each) than polymorphisms at 904 (35%) and 836 (20%). Interestingly, nine sporadic cases with no mutations also had the G691S polymorphism, which is the only SNP associated with an amino acid change. Further, all cases that had G691S polymorphism also had S904S polymorphism. Although G691S is not considered an oncogenic mutation, a functional role for this SNP has not been entirely ruled out. In fact Elsei et al. reported a significantly higher allelic frequency of G691S among sMTC when compared to normal controls suggesting a putative role for this SNP as a genetic modifier. However, our study has the drawback of characterizing these polymorphisms only among patients’ with MTCs without

Mutations seen among patients with pheochromocytoma and paraganglioma at a referral center from India.

Determining the mutational status of susceptibility genes including RET, VHL, SDHx (SDHB, SDHC, SDHD) among patients with pheochromocytoma/paraganglioma (PCC/PGL) is gaining importance. These genes have not been systematically characterized among patients with PCC/PGL from India. The aim of the work was to screen the most frequently mutated genes among patients with PCC/PGL to determine the frequency and spectrum of mutations seen in this region. Fifty patients with PCC/PGL treated at our tertiary care hospital between January 2010 and June 2012 were screened for mutations in susceptibility genes using an algorithmic approach. Thirty-two percent (16/50) of patients were found to be positive for mutations including mutations among RET (n=4), VHL (n=6), SDHB (n=3), and SDHD (n=3) genes. None of these patients were positive for SDHC mutations. A significant association was found between young patients with bilateral tumors and VHL mutations (p=0.002). Two of the 3 patients with extra-adrenal SDHB associated tumors, had unique mutations, viz., c.436delT (exon 5) and c.788_857del (exon 8), one of which was malignant. High frequency of mutations seen among patients in this study emphasizes the need to consider mutational analysis among Indian patients with PCC/PGL.

Metastatic parathyroid carcinoma treated with radiofrequency ablation: A novel therapeutic modality.

Parathyroid carcinoma (PCA), accounting for less than one per cent of all endocrine malignancies, is a rare cause of primary hyperparathyroidism. A diagnosis of parathyroid carcinoma may be challenging in the presence of localised disease and involves a histological diagnosis based on capsular, vascular, or perineural invasion or the presence of metastasis. Distant metastasis remains a rare presentation, with the lung being the most common site. Surgery remains the treatment of choice as radiotherapy and chemotherapy have proved to be of limited benefit in metastatic disease. This case reports suggests that radiofrequency ablation has the potential to be a novel and effective treatment option in these patients.

Preoperative Ultrasonography Assessment of Vocal Cord Movement During Thyroid and Parathyroid Surgery

Wereadwithinterestthearticle‘‘Preoperativeultrasonographyassessment of vocal cord movement during thyroid andparathyroid surgery’’ by Cheng et al. [1]. We congratulate theauthors on using a noninvasive modality for evaluating vocalcords preoperatively with no added cost or time. It was apatient-friendly initiative in a resource-constrained environ-ment. Patients with vocal cord palsy may be asymptomatic.Indirect laryngoscopy is not adequate in all cases. If it isperformed routinely, it becomes costly, as do visits tooutpatient clinics. There is also patient discomfort to beconsidered as it is an invasive procedure. ENT surgeons arenot widely available; and even if available, these patientsare not a priority. The cost incurred, the discomfort for thepatient, and the physician’s expertise are issues associatedwith performing regular fiberoptic bronchoscopy. Thequestion of attending surgeons performing indirect laryn-goscopy in terms of medicolegal purposes continues to beconsidered by many surgical societies. If the same logisticsare adopted for ultrasonography, the question arises whe-ther it would be more prudent to have the vocal cordexamined by radiologists. We have a few queries related tothe present study [1–6].Nonrecurrent laryngeal nerves are rare [2]. Did the Ysign done for evaluation increase the time taken to performultrasonography (USG)? Did the authors use USG forperforming guided fine-needle aspiration cytology? Werethe vocal cords evaluated postoperatively with USG? Ifyes, then what was the sensitivity and specificity of USGpostoperatively [4]? Was pulsed Doppler used to quantifythe tissue displacement velocity in the vibrating vocal foldsection [3]? Did the authors perform the Valsalva maneu-ver to adduct the vocal cords? Did the severe sniffing resultin displacement of the probe, thereby causing difficultywhen performing USG?References

Role of cortical sparing adrenalectomy and novel variant of mutation in patient with von Hippel-Lindau disease.

Neurofibromatosis type 1 is the most common phakomatoses and is inherited in autosomal dominant fashion with complete penetrance. Secondary hypertension is common in these patients due to various causes including adrenal tumors. Pheochromocytoma is a rare catecholamine producing tumor seen in 0.5% to 5% of patients with neurofibromatosis. The combination of pheochromocytoma with neurofibromatosis is rarely reported in the literature. We recently encountered an elderly lady with this combination who successfully underwent adrenalectomy. We report the case for the uncommon occurrence and to highlight the relevant literature review about pheochromocytoma in neurofibromatosis.