Treatment Response following Radioactive Iodine Therapy in Miliary versus Macronodular Pulmonary Metastases in Papillary Thyroid Carcinoma.

Background Pulmonary metastases in papillary thyroid carcinoma have two common presentations-micro/miliary (MM) and macronodular metastases (MN). The mainstay of treatment, posttotal thyroidectomy, is multiple radioactive iodine ablations (RAIA) every 6 to 12 months. Response assessment is determined by decline in stimulated serum thyroglobulin levels (sTg), disease regression on chest x-ray (CXR), computed tomography thorax, or whole body iodine scintigraphy (TWBS). Aim This study aims to assess the difference in response to RAIA based on the pattern of presentation. Methodology Retrospective analysis of patients from January 2008 to July 2017 was done. Patients with pulmonary metastases treated with RAIA (3700MBq per therapy as opposed to theAmerican Thyroid Association recommendation of 7400MBq per therapy) and a minimum follow-up of 8 months were included. The initial and the final sTg, TWBS, and CXR were analyzed for both groups. Final outcome in terms of complete response, disease regression, static disease, and disease progression was determined. Results Of the total of 1,793 patients, 71 were included. There were 43 females and 28 males. The median age was 39 years and the range was 14 to 79 years. Forty-five (63.3%) patients had MM and 26 (36.6%) patients had MN disease. The average number of therapies was three and maximum follow-up period was 15 years. Of the 45 MM patients, 1 had progression, 7 were static, 23 had regression, and 14 had complete response. Of the 26 MN patients, 22 had progression, 2 were static, 1 had regression, and 1 had complete response. Conclusion MM metastases, when compared with MN disease, respond to RAIA with a better outcome. In addition to achieving comparable response with a lower dose per therapy, there were no radiation-related long-term complications reported.

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.

Stem cells: a regenerative pharmaceutical.

Stem cells (SC), found in both adult and fetal tissues, are self-renewing elements that can generate the various cell types in the body. There are 3 classes of SC: totipotent, multipotent, and pluripotent. The SC with a significant developmental potential are the embryonic stem (ES) cells, which are derived from the early stages of mammalian embryo. SC possess regenerative properties and this offers unprecedented opportunities for developing medical therapies for debilitating diseases. Hematopoietic SC have been used successfully in bone marrow transplants for over 40 years. Pluripotent SC offer renewable source of replacement of cells and tissues to treat a myriad of diseases. However there are limiting factors. Adult SC are rare and cannot multiply as the ES. Pluripotent SC have great therapeutic potential, but face technical challenges. A serious concern is the ethical issue since they are derived from human embryos or fetal tissue. Quite often SC have been targets of mutations and risk carcinogenesis. Various markers have been identified based on the uniqueness of SC receptors and in vivo tracking studies using nanocolloids and radioactive tracers have been performed. Though 111In-oxine has been used to image SC transplants, PET with a high spatial resolution would be ideal. Currently 2 agents are being studied, 18F-FDG and 64Cu-Pyruvaldehyde bi(N4-methylthiosemicarbazone). The following few pages bring forth the various limitations and summarize progress made in SC utilization so as to create awareness of SC research in ISORBE community and to foster strategy that ISORBE community can disseminate information and exchange knowledge on radio labeled SC.

99mTc-Fanolesomab: affinity, pharmacokinetics and preliminary evaluation.

Localization of infection is critical for both diagnosis and treatment. Several radioactive compounds such as (67)Gallium citrate, (111I)ndium and (99m)Technetium-labeled leukocytes, peptides and antibodies have been used to localize sites of bacterial infection and phlegmons when anatomical imaging techniques failed. With labeled leukocytes the major concern besides the cost, was the in vitro procedure requiring more than 2 h and trained personnel to handle blood samples. Such limitations paved the way for the emergence of new agents like human immunoglobulin, interleukin-1, peptides and monoclonal antibodies. Following the intensive study of 10 monoclonal antibodies the anti SSEA-1 antibody specific for CD15 antigen was found to have a high Kd value of 1.6x10(-11) M for human neutrophils. Labeling of anti CD15 antibody (NeutroSpec) with (99m)Tc and its FDA approval was a boon to diagnostic imaging as it promised to eliminate many of the well known drawbacks of the in vitro WBC labeling. This antibody has a large number of antigenic binding sites: 5.1x10(5) per circulating human neutrophil. It has been established that very little CD15 antigen is expressed on the other blood cell lines. Upon intravenous administration to patients there was no adverse reaction except in those with underlying cardiovascular compromise or chronic pulmonary obstructive disease. Another advantage is that, this particular monoclonal antibody has not produced significant human antimouse antibody in research volunteers and patients. Twenty-four hour imaging, SPECT or planar was not required. The following pages describe the various stages of the research activity carried out towards NeutroSpec.

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.

Phaeochromocytoma: experience from a referral hospital in southern India.

BACKGROUND: Phaeochromocytoma has been traditionally called the 'Tumour of Tens'. Many investigators have reported the prevalence of extra-adrenal phaeochromocytoma to be more than 10%. METHODS: All consecutive adult patients diagnosed to have phaeochromocytoma by the departments of endocrinology and surgical endocrinology of the Christian Medical Hospital, India, over a period of 10 years from 1988 to 1998, were included in the study. RESULTS: A total of 30 patients were diagnosed to have phaeochromocytoma. Extra-adrenal phaeochromocytoma accounted for 26.6% of cases, Ten per cent of cases were bilateral, 6.6% were malignant and one patient had a familial tumour (multiple endocrine neoplasia IIB). The tumours were localized pre-operatively in all patients. Multicentric extra-adrenal tumours were not found in this series. All patients except one were explored by the anterior transperitoneal approach. Persistent hypertension was noted in 30% of patients. CONCLUSIONS: Our series shows a higher prevalence (26.6%) of extra-adrenal tumours than the traditionally described 10%. With accurate pre-operative localization, a transperitoneal approach may not be necessary. The laparoscopic approach needs to be evaluated in light of these findings.

Association of a bleeding Meckel's diverticulum with upper thoracic vertebral anomalies and tetralogy of Fallot.

A 14-month-old child presented with recurrent episodes of melaena, upper thoracic hemivertebrae, and tetralogy of Fallot. The presence of the upper thoracic hemivertebrae led to the suspicion of intestinal duplication. However, technetium (Tc99m) scintigraphy revealed a Meckel's diverticulum. Following laparotomy and excision of the diverticulum, the histopathological examination confirmed the diagnosis.