Nylla Shanthly

Recent Trends in Soft-Tissue Infection Imaging

This article discusses the current techniques and future directions of infection imaging with particular attention to respiratory, central nervous system, abdominal, and postoperative infections. The agents currently in use localize to areas of infection and inflammation. An infection-specific imaging agent would greatly improve the utility of scintigraphy in imaging occult infections. The superior spatial resolution of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) and its lack of reliance on a functional immune system, gives this agent certain advantages over the other radiopharmaceuticals. In respiratory tract infection imaging, an important advancement would be the ability to quantitatively delineate lung inflammation, allowing one to monitor the therapeutic response in a variety of conditions. Current studies suggest PET should be considered the most accurate quantitative method. Scintigraphy has much to offer in localizing abdominal infection as well as inflammation. We may begin to see a gradual increase in the usage of (18)F-FDG-PET in detecting occult abdominal infections. Commonly used modalities for imaging inflammatory bowel disease are scintigraphy with (111)In-oxine/(99m)Tc-HMPAO labeled autologous white blood cells. The literature on central nervous system infection imaging is relatively scarce. Few clinical studies have been performed and numerous new agents have been developed for this use with varying results. Further studies are needed to more clearly delineate the future direction of this field. In evaluating the postoperative spine, (99m)Tc-ciprofloxacin single-photon emission computed tomography (SPECT) was reported to be >80% sensitive in patients more than 6 months after surgery. FDG-PET has also been suggested for this purpose and may play a larger role than originally thought. It appears PET/computed tomography (CT) is gaining support, especially in imaging those with fever of unknown origin or nonfunctional immune systems. Although an infection-specific agent is lacking, the development of one would greatly advance our ability to detect, localize, and quantify infections. Overall, imaging such an agent via SPECT/CT or PET/CT will pave the way for greater clinical reliability in the localization of infection.

Afferent loop syndrome: the role of Tc-99m mebrofenin hepatobiliary scintigraphy.

Afferent loop syndrome is caused by intermittent mechanical obstruction of the afferent loop of a gastrojejunostomy and may present early as an acute type or late as a chronic type. The authors describe two patients who were examined for a history of bilious vomiting after gastrojejunostomy, and who were thought to have afferent loop syndrome (chronic type) based on clinical findings. Results of routine investigations, such as upper gastrointestinal endoscopy, and ultrasonography were inconclusive. Findings from the barium meal follow-through studies were normal in the first patient and revealed a dilated duodenum in the second patient. Tc-99m bromotriethyl-iminodiacetic acid has been used to identify afferent loop obstruction as represented in these studies.

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.

Toxic Thyroid Adenoma in McCune-Albright Syndrome

Case A 17-year-old lady presented with history of palpitations, tremors, heat intolerance and weight loss, all of two months duration. She also had a history of fractures, following a trivial trauma. The first fracture was in left forearm at the age of 10 years, which was managed conservatively and the second was in neck of left femur two months ago, for which she had undergone closed reduction and internal fixation [Table/Fig-1]. She also had noticed a left facial swelling since childhood, which had been gradually progressive and was operated two years back. Her age of menarche was 13 years and she had regular menstrual cycles.

Abnormal Appearance of Spinal Hemangioma Mimicking Metastasis in Bone Scintigraphy and SPECT-CT: Case Report

Study design: Case reports of abnormal appearance of hemangioma in thoracolumbar spine in bone scintigraphy. Objective: To report an unusual presentation of spinal hemangioma mimicking metastasis in bone scintigraphy and SPECT-CT. Summary of back ground data: Spinal hemangiomas are usually incidental findings. Most of them are asymptomatic and bone scintigraphy will be normal in majority of them. In the back ground of an underlying malignancy, an abnormal hot spot in bone scan always arouse a high suspicion of bone metastasis. Methods: Two middle aged ladies, treated for carcinoma cervix and carcinoma breast respectively, were undergoing regular follow ups. One patient had complaints of back pain on and off and her bone scan showed abnormal increase in tracer uptake in L1 vertebra suspicious of metastasis. Second lady had suspected intra abdominal metastatic disease and her bone scan showed abnormal increase in tracer uptake in thoracolumbar spine mimicking metastasis. Results: Both patients underwent further detailed evaluations and MRI study of spine was reported as hemangioma and PET-CT ruled out the possibilities of recurrent or metastatic malignancy. During further follow up, both patients were disease free. Conclusion: Hemangioma of spine appearing as a hot spot in bone scan is rare. In the back ground of a malignancy, a ‘hot’ lesion can be studied better with metabolic imaging with PET – CT which could dispel the suspicion of a metastatic focus quite clearly. MRI could also give a diagnostic clue.

Comparison of glomerular filtration rate measured by plasma sample technique, Cockroft Gault method and Gates' method in voluntary kidney donors and renal transplant recipients

Background: There are numerous methods for calculation of glomerular filtration rate (GFR), which is a crucial measurement to identify patients with renal disease. Aims: The aim of this study is to compare four different methods of GFR calculation. Settings and Design: Clinical setup, prospective study. Materials and Methods: Data was collected from routine renal scans done for voluntary kidney donors (VKD) or renal transplant recipients 6 months after transplantation. Following technetium-99m diethylene triamine penta acetic acid injection, venous blood samples were collected from contralateral arm at 120, 180, and 240 min through an indwelling venous cannula and direct collection by syringe. A total volume of 1 ml of plasma from each sample and standards were counted in an automatic gamma counter for 1 min. Blood samples taken at 120 min and 240 min were used for double plasma sample method (DPSM) and a sample taken at 180 min for single plasma sample method (SPSM). Russells formulae for SPSM and DPSM were used for GFR estimation. Gates’ method GFR was calculated by vendor provided software. Correlation analysis was performed using Pearsons correlation test. Results: SPSM correlated well with DPSM. GFR value in healthy potential kidney donors has a significant role in the selection of donors. The mean GFR ± (standard deviation) in VKD using SPSM, DPSM, camera depth method and Cockroft Gault method was 134.6 (25.9), 137.5 (42.4), 98.6 (15.9), 83.5 (21.1) respectively. Gates’ GFR calculation did not correlate well with plasma sampling method. Conclusions: Calculation of GFR plays a vital role in the management of renal patients, hence it was noted that Gates GFR may not be a reliable method of calculation. SPSM was more reliable. DPSM is reliable but cumbersome. It is difficult to accurately calculate GFR without a gold standard.

Iodine-131MIBG SPECT/CT in neuroendocrine tumours: An institutional experience

Context: Radiolabelled metaiodobenzylguanidine (MIBG) is commonly used for imaging of neuroendocrine tumors (NETs). The hybrid imaging with single photon emission computerized tomography/computerized tomography (SPECT/CT) co-registration can give that additional edge to this functional imaging modality. Aims: To study the additional value of 131I-MIBG SPECT/CT scintigraphy in evaluation of NETs. Settings and Design: We performed a retrospective study of the scintigraphic data of patients referred to our department for detection and follow-up of NETs from 2004 to 2008. Materials and Methods: Total number of studies were 370. Twenty-eight patients with equivocal findings on planar imaging had undergone additional SPECT/CT imaging. The contribution made by SPECT/CT imaging in these studies was analyzed. Results: In 27 of 28 cases, SPECT/CT provided vital additional information. Conclusions: We concluded that SPECT/CT co-registration helps in exclusion, identification, and localization of primary and metastatic NETs. It differentiates physiological from pathological tracer distribution. It helps increase the confidence in reporting, especially in equivocal findings on planar imaging.

Stimulated serum thyroglobulin levels versus unstimulated serum thyroglobulin in the follow-up of patients with papillary thyroid carcinoma

Serum thyroglobulin (Tg) and thyroid whole-body radioiodine scintigraphy (TWBS) are used in the follow-up of patients with papillary thyroid carcinoma (PTC) after total thyroidectomy. Symptoms of hypothyroidism are frequent as patients discontinue levothyroxine 1 month before visit, favoring the use of unstimulated serum Tg (uSTg) only. This study was done to determine the reliability of stimulated serum Tg levels (sSTg) over uSTg. A total of 650 patients with PTC came for follow-up between June 2011 and 2016. In those who had levels of uSTg and sSTg months measured within an interval of median of 3 months (range from 1 to 8 months), risk stratification was done as per the American Thyroid Association guidelines 2015. Intervention was based on a cutoff value of sSTg >10 ng/ml in our institution and the same was used for data analysis. Out of 650 patients, 106 had paired Tg values. Low-, intermediate-, and high-risk groups comprised 40, 31, and 35 patients, respectively. The sSTg >10 ng/ml with uSTg <10 ng/ml in the same patient was noted in 22.5% (9/40) of the low-risk, 41.9% (13/31) of the intermediate-risk, and 14.2% (5/35) of the high-risk groups. The levels were corroborated with tumor burden as determined by additional clinical, ultrasonography neck, and TWBS findings. Our study highlights the superiority of sSTg over uSTg in the follow-up of PTC patients. Follow-up with uSTg alone may result in underestimating the tumor burden.

A thyroid nodule mimic.

A 48-year-old man, known for well-controlled hypertension over the past 8 years, was evaluated for low back pain. The clinical examination was unremarkable except for a 4 cm right-sided nodule in the region of the thyroid gland. So a clinical diagnosis of right solitary thyroid nodule was made and investigated. His biochemistry showed a high serum calcium level of 11.4 mg/dL (8.3–10.3) and phosphate of 1.4 mg/dL (2.5–5.5) with intact parathormone (PTH) …