Long-term disease-free survival after MIBG therapy for metastatic pheochromocytoma.

Pheochromocytomas are rare tumours originating in chromaffin cells, representing 0.1%-1% of all secondary hypertension cases. The majority are benign and unilateral, characterised by the production of catecholamines and other neuropeptides. Mainly located in the adrenal gland, they are more frequent between the third and fifth decades of life. Iodine-131 metaiodobenzylguanidine (131I-MIBG), a radiopharmaceutical agent used for scintigraphic localisation of pheochromocytomas, has been employed to treat malignant pheochromocytomas since 1983 in a few specialised centres around the world. We reviewed our clinical experience in one such case of a young lady who presented with history of abdominal pain, headache and lower back pain. On evaluation, ultrasonography revealed a right adrenal mass and elevated urine vanillylmandelic acid levels. Following surgical resection and histopathological confirmation of pheochromocytoma, MIBG scintigraphy revealed osseous metastases and hence, she underwent 131I-MIBG therapy.

Therapeutic Response to PRRNT in a Rare Case of Metastatic Renal Neuroendocrine Carcinoma.

Neuroendocrine tumors (NETs) are a rare spectrum of neoplasms that are characterized by neuroendocrine and neural differentiation. The treatment can be challenging in view of the heterogeneity in differentiation and behavior. Primary renal origin NETs are rare and only a few cases have been reported in the literature. There is limited knowledge on their presentation and response to various lines of treatment. We report a case of a patient with a metastatic renal NET from a rare histological subtype of large cell neuroendocrine carcinoma, known to cause aggressive disease with poor prognosis. A multimodality treatment approach was followed. In spite of surgical management and second-line chemotherapy, the disease progressed. The patient subsequently received peptide receptor radionuclide therapy (PRRNT) using lutetium-177 DOTATATE, following which the patient demonstrated a remarkable clinical and radiological response and is stable to date. In a rare tumor with poor prognosis, the relevance of theranostics and the efficacy of targeted therapies like PRRNT are noteworthy.

Analysis of discordant PET and CT findings in 18F-FDG PET-CT scans in the management of oncology patients.

BACKGROUND: Discordant findings are often noted between PET-CT and CT images of 18F-FDG PET-CT scans and cause ambiguity in image interpretation. This study aimed at determining the significance of these findings in the management of oncology patients. CONTEXT: Discordant findings are often noted between PET-CT and CT images of 18F-FDG PET-CT scans and cause ambiguity in image interpretation. AIM: This study aimed at determining the significance of these findings in the management of oncology patients. METHODS: This was an observational, descriptive study. Hence, retrospective analysis of all discordant findings in oncology patients undergoing a PETCT imaging between Jan 2013 and Jan 2016 was done. Those patients who had a follow-up period of minimum 1 year in either of the following forms - repeat PETCT imaging, other radiological imaging, clinical, or histopathological evidence were included. From all the discordant lesions, the sensitivity, specificity, positive predictive, negative predictive value, and accuracy of both PET-CT and CT modalities were determined. RESULTS: Of 348 discordant lesions, 16.7% was noted in soft tissues, 25% in viscera, 28.7% in lungs, 14.1% in lymph nodes, and 15.5% in bones. At the end of follow-up, 15.2% lesions were PET true positive, 57.5% PET true negative, 10.1% CT true positive lesions, 13.8% CT true negative, and 3.4% were inconclusive. CONCLUSION: 18F-FDG PET-CT is superior to CT imaging and should be considered as the first-line imaging modality in oncology patients.

Validation of Deauville Score for Response Evaluation in Hodgkin's Lymphoma.

Context: Positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG) for treatment monitoring in patients with lymphoma is one of the most well-developed clinical applications. Deauville five-point score (DS) is recommended for response assessment in international guidelines. DS gives the threshold for adequate or inadequate response to be adapted according to the clinical context or research question. Aims: We aimed to validate DS in Hodgkin's lymphoma (HL) by retrospectively assigning this score to F-18 FDG PET-computed tomography (CT) studies done before 2016 and analyzing its concordance with the line of management. The secondary aim was to assess the reproducibility of DS in the interpretation of PET-CT scans. Subjects and Methods: A total of 100 eligible consecutive patients underwent F-18 FDG PET-CT scans between January 2014 and December 2015. Their interim, end of treatment, and follow-up PET scans were retrospectively visually analyzed and assigned DS by three nuclear medicine physicians. Concordance was defined as agreement between the DS assigned and the line of treatment. Interobserver variability was calculated using weighted Kappa and presented with 95% confidence interval. Results: Among 212 scans assigned DS, 165 scans showed agreement between the DS and line of treatment. Of these, 95.2% of scans scored DS 1-3 were kept on following or the same treatment plan was continued and patients did well. Among the scans that showed discordance, 24 scans scored DS 4/5 were continued on the same treatment regimen and the next assessment showed disease progression. Conclusions: Our study confirmed that DS is a useful tool to aid in reporting F-18 FDG PET-CT in the management of HL with good positive and negative predictive values. This study also demonstrated good interobserver agreement.

Comparison of Lymphatic Drainage of the Lower Limbs After Soft Tissue Reconstruction by Microvascular Muscle Flap Versus Fasciocutaneous Flaps.

INTRODUCTION: Complex traumatic injuries of the lower limb are increasingly being salvaged. The common long-term morbidity includes secondary lymphedema. The role of microvascular flaps is often discussed for lymph flow restoration. However, the differential effect of using muscle flap versus fasciocutaneous flap in the lower-limb trauma to avoid secondary lymphedema is not studied. METHODS: Forty patients who underwent microvascular flap reconstruction were reviewed retrospectively to obtain data regarding clinical demographics and surgical procedure. Assessment for presence of clinical lymphedema was done. The lymphatic drainage in all these patients was assessed by 99mTc lymphoscintigraphy. RESULTS: Of the 40 patients included in the study, group A (n = 23) underwent muscle-based free flap reconstruction, and group B (n = 17) had fasciocutaneous flaps. Clinical lymphedema was present in 21 patients, of which 18 were of group A and 3 of group B. On lymphoscintigraphy, 14 patients had either partial or complete obstruction in the reconstructed lower limb, 11 in group A and 3 in group B. All of them (n = 14) were found to have associated clinical lymphedema. The association of clinical lymphedema (P < 0.001) and obstructive pattern on lymphoscintigraphy (P < 0.05) with muscle flaps was found to be statistically significant. CONCLUSIONS: With the advancement in surgery and techniques, not only salvageability but also stable and morbidity free outcomes are the goals. Fasciocutaneous flaps may have better lymphatic outcomes than the muscle-based flaps, and the criteria for lower-limb reconstruction can be reformed to include simultaneous soft tissue and lymphatic reconstruction.

Utility of positron emission tomography-computed tomography in the evaluation of fever of unknown origin in a resource-limited tropical nation.

Positron emission tomography-computed tomography (PET-CT) has been used as an imaging modality in workup of fever of unknown origin (FUO). The aim of our study is to evaluate the diagnostic utility of PET-CT in FUO workup in a resource-limited setting. We also looked at laboratory parameters as predictors of contributory PET-CT scans and propose an algorithm for evaluation of FUO in resource-limited tropical regions. This retrospective observational study included patients admitted for FUO workup under general medicine in a teaching hospital in South India from June 2013 to May 2016. PET-CT was done when the patient remained undiagnosed after a detailed clinical assessment and first- and second-tier investigations. Among 43 patients included in our study, a definite diagnosis was established in 74% (32). Noninfectious inflammatory diseases, infections, malignancies, and miscellaneous diseases were diagnosed in 37.2% (16/43), 23.3% (10/43), 9.3% (4/43), and 4.7% (2/43), respectively. Tuberculosis was the single most common disease seen in 20.9% (9/43). PET-CT scans were contributory toward establishment of final diagnosis in 90.7% (39/43). High C-reactive protein (CRP) and aspartate aminotransferase (AST) levels were associated with contributory PET-CT scans (P = 0.006 and 0.011, respectively). PET-CT delineating organ/tissue for diagnostic biopsy was associated with final diagnosis of infectious disease (P = 0.001). Sensitivity, specificity, and positive and negative predictive value of PET-CT scans were 76.9% (20/26), 33.3% (2/6), 83% (20/24), and 25% (2/8), respectively. High CRP and AST were predictors of contributory PET-CT scans. PET-CT scans have high sensitivity and positive predictive value when used in evaluation of FUO. Although it is a useful tool in FUO workup, especially in the diagnosis of tropical infections, PET-CT should be done after a comprehensive clinical assessment and basic investigations.

Diffuse Infiltrative Non-mass-like Brain Parenchymal Lesions on MRI: Differentiating Lymphomatosis Cerebri from its Mimics.

OBJECTIVES: Diffuse infiltrative "non-mass-like" parenchymal lesions on MRI brain are a known presentation of an aggressive condition called lymphomatosis cerebri (LC) but are often misdiagnosed due to its non-specific clinical and imaging findings. We aim to identify clues to differentiate lymphomatosis from its less aggressive mimics based on imaging features. MATERIAL AND METHODS: MRI brain studies showing diffuse infiltrative "non-mass-like" parenchymal lesions between January 2013 and March 2020 were retrospectively identified and read for lesion location, signal characteristics, and enhancement pattern by two radiologists. Additional findings on MRI spine and whole-body fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) were recorded wherever available. The clinical diagnosis, patient demographics, symptoms, laboratory and histopathology results, treatment details, and follow-up details were also noted. RESULTS: Of the 67 patients, 28 (41.7%) were diagnosed with lymphomatosis. The remaining 39 (13.4%) patients were classified as non-lymphomas (infective, vasculitis, and inflammatory conditions). Diffusion restriction on MRI (20/67, P = 0.007) and increased regional activity on FDG PET-CT (12/31, P = 0.017) were the two imaging parameters found to significantly favor lymphomatosis over other conditions, whereas the presence of microhemorrhages on susceptibility-weighted imaging was significantly associated with vasculitis (P = 0.002). Rapid clinical or imaging deterioration on a short trial of steroids (P = 0.00) was the only relevant clinical factor to raise an early alarm of lymphomatosis. Positive serological markers and non-central nervous system systemic diseases were associated with non-lymphomatous diseases. CONCLUSION: LC and its less aggressive mimics can be differentiated on diffusion-weighted imaging-MRI and PET-CT when read in conjunction with rapid progression of clinical features, serological workup, and systemic evaluation.

Myelofibrosis and Pancytopenia Associated With Primary Hyperparathyroidism.

OBJECTIVE: Primary hyperparathyroidism (PHPT) has varied clinical presentations. Hematologic abnormalities secondary to PHPT have been described before. However, pancytopenia as the initial presentation has rarely been reported. We report a patient with PHPT who presented for evaluation of pancytopenia. METHODS: Histopathology of the bone marrow at presentation is described. Bone biochemistry results and the hematologic profile before and after curative parathyroidectomy are presented. RESULTS: A 48-year-old woman presented with pancytopenia (hemoglobin, 6.3 g/dL; total leucocyte count, 3000 cells/mm3; and platelet count, 60 000 cells/mm3), and her bone marrow study showed marrow fibrosis. Biochemical evaluation revealed hypercalcemia (15.5 mg/dL), hypophosphatemia (2.2 mg/dL), and elevated total alkaline phosphatase (4132 U/L). Bone mineral density assessment by dual-energy X-ray absorptiometry scan revealed osteoporosis at all 3 sites, which was more severe in the distal one third of the forearm. Further investigations confirmed the diagnosis of PHPT (serum parathyroid hormone, 2082 pg/mL). Following curative parathyroidectomy, in addition to normalization of calcium, there was restoration of all 3 hematologic cell lines at 3 months. CONCLUSION: Pancytopenia may be a rare manifestation of PHPT. Thus, it may be prudent to evaluate the calcium profile in patients with chronic refractory anemia and pancytopenia.

F-18 FDG PET-CT for response evaluation in head and neck malignancy: Experience from a tertiary level hospital in south India.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) accounts for 90% of head and neck cancers. There has been no established qualitative system of interpretation for therapy response assessment using PET-CT for HNSCC. AIM: To assess response evaluation of nodal status in post-treatment PET-CT scans in HNSCC using a 5-point Likert scale (Deauville score [DS]). METHODS AND RESULTS: Retro-prospective analysis was performed of the nodal status of pre and post-RT PET-CT in patients diagnosed with HNSCC (n = 43) from May 2013 to March 2018. All eligible patients underwent a pre-RT PET-CT scan before the start of RT. Another post-RT PET-CT scan was performed 12 weeks after the completion of RT. The median time from completion of radiotherapy (RT) to post-RT PET-CT was 92 days; 80% of the patients had their post-RT PET-CT scan between 77 and 147 days after therapy. Of 43 patients (M/33, F/10, age range 18 to 80 years (median 54 years) selected for the study, good concordance was noted between DS and clinical response in these patients. The change in SUV from pre-RT PET to post-RT PET was analyzed using a paired t-test. The P-value was found to be statistically significant while comparing pre and post-RT SUVmax levels showing that RT had significantly reduced the SUVmax levels of the nodes in DS 2-3 groups whereas the number of patients was too small to allow a reliable calculation in DS 4-5 groups. It was found that 36/39 patients with DS 1-3 had no nodal recurrence showing a high NPV of 92.3%. Of the four patients with DS 4-5, all had active disease showing PPV of 100%. Applying Fisher's exact test, the P-value was found to be .004. CONCLUSION: DS seems to satisfy the requirements for a simple qualitative method of interpreting PET scans and for identifying patients requiring neck dissection. Consensus regarding qualitative assessment would facilitate standardization of PET reporting in clinical practice and enable comparative multicentric studies.

Papillary Thyroid Carcinoma in Children: Clinicopathological Profile and Outcomes of Management.

BACKGROUND: We aim to analyze the clinicopathological profile and outcomes of management for children with papillary thyroid carcinoma (PTC). METHODS: Relevant clinical data of children ≤ 18 years of age managed for PTC between January 2006 and July 2018 as well as details of their follow-up till December 2019 were retrospectively collected and analyzed. RESULTS: There were 82 children with PTC that were managed during the study period. At presentation, 39 (47.6%) had cervical lymphadenopathy, while 9 (11%) had systemic metastasis. Majority of patients 39 (47.6%) underwent total thyroidectomy with a selective neck dissection, while total thyroidectomy alone was performed in 26 (31.7%). Following surgery, hypocalcemia was seen in 39 (47.6%): 28 (34.1%) were temporary, while 11 (13.4%) were permanent. Twenty-eight (34%) developed persistent disease after surgery and 131I therapy. Significant risk factors for persistence and metastatic disease were metastatic cervical lymph node at presentation (p = 0.002) and tumor size (p = 0.014), respectively. The mean duration of follow-up was 60.3 (range 12-150) months with a mean overall disease-free survival of 60 months (95% CI 57.11, 77.95). CONCLUSION: Children with papillary thyroid cancers present with aggressive disease, 47.6% with cervical nodal metastasis and 11% with distant metastasis in this cohort. The rate of post-thyroidectomy hypocalcemia in this study is substantial, and efforts to reduce it are actively being pursued. The presence of metastatic cervical lymph node at presentation (p = 0.002) and tumor size (p = 0.014) were the only significant risk factors for persistent and metastatic disease, respectively, in this study.

Does Baseline PTH Influence Recovery of Bone Mineral Density, Trabecular Bone Score and Bone Turnover Markers? A Prospective Study Following Curative PArathyroidectomy in Primary Hyperparathyroidism.

OBJECTIVE: This prospective study was carried out to assess trabecular bone score, bone mineral density (BMD), and bone biochemistry in Indian subjects with symptomatic primary hyperparathyroidism (PHPT), and to study the influence of baseline parathyroid hormone (PTH) on recovery of these parameters following curative surgery. METHODS: This was a 2-year prospective study conducted at a tertiary care centre in southern India. Baseline assessment included demographic details, mode of presentation, bone mineral biochemistry, BMD, trabecular bone score (TBS), and bone turnover markers (BTMs). These parameters were reassessed at the end of the first and second years following curative parathyroid surgery. RESULTS: Fifty-one subjects (32 men and 19 women) with PHPT who had undergone curative parathyroidectomy were included in this study. The mean (SD) age was 44.6 (13.7) years. The TBS, BTMs, and BMD at lumbar spine and forearm were significantly worse at baseline in subjects with higher baseline PTH (≥250 pg/mL) when compared to the group with lower baseline PTH (<250 pg/mL). At the end of 2 years, the difference between high versus low PTH groups (mean ± SD) persisted only for forearm BMD (0.638±0.093 versus 0.698±0.041 g/cm2; P =.01). However, on follow-up visits in the first and second year after curative parathyroidectomy, there was no significant difference in BTMs, BMD at the femoral neck, lumbar spine, and TBS between the 2 groups stratified by baseline PTH. CONCLUSION: The BMD at the forearm remained significantly worse in individuals with high baseline PTH even at 2 years after surgery, while other parameters including TBS improved significantly from baseline. ABBREVIATIONS: 25(OH)D = 25-hydroxyvitamin D; BMD = bone mineral density; BMI = body mass index; BTMs = Bone turnover markers; CTX = C-terminal telopeptide of type 1 collagen; DXA = dual energy X-ray absorptiometry; P1NP = N-terminal propeptide of type 1 procollagen; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; TBS = trabecular bone score.

Ga-68 DOTATATE Positron Emission Tomography-Computed Tomography Imaging in Oncogenic Osteomalacia: Experience from a Tertiary Level Hospital in South India.

AIM: Utility of Ga68 DOTATATE PETCT imaging to localise cause for oncogenic osteomalacia (OOM). MATERIALS AND METHODS: Retrospective analysis between March 2015 to March 2018 of all patients with a clinical diagnosis (based on a combination of clinical history, hypophosphatemia and elevated FGF-23 values) of OOM who underwent Ga-68 DOTATATE PET/CT. RESULTS: Total of 27 patients had undergone Ga-68 DOTATATE PET/CT imaging in our centre from March 2015 to March 2018. Of these 16 patients with clinically suspected oncogenic osteomalacia were included in our study. Age range 18-61 years of which 12 were males. Total of 13 (81.25%) patients were found to be positive on imaging for a possible mesenchymal tumour. Most common site of tumour was the lower limb (76%). Most common presenting symptom was bone pain (81%) followed by muscle weakness (19%). Overall, 10 patients underwent surgery, all of whose biopsy was reported as phosphaturic mesenchymal tumour. During the three month follow up, serum phosphorous measured in 15/16, post-surgical/ medical treatment had normalised in all except two patients who had undergone only medical therapy with neutral phosphate. Fall in FGF-23 was more pronounced in surgically treated patients as compared to those who received medical treatment. CONCLUSION: Ga68-DOTATE PET/CT is a useful investigatory modality for localizing cause for oncogenic osteomalacia.

An uncommon cause of polyarthralgia.

Tumour induced osteomalacia (TIO) is a paraneoplastic syndrome characterized by renal phosphate wasting and hypophosphatemic osteomalacia, caused by FGF-23 (Fibroblast growth factor-23) producing mesenchymal tumours. Here, we report the case of a 40 year old lady referred by her family physician for multiple joint pains of 2 years duration. There was no evidence of inflammatory arthritis. Biochemical investigations revealed low phosphorus, with raised alkaline phosphatase and high levels of FGF-23. As a TIO was considered likely, functional imaging with a DOTATATE PET scan was done, which revealed a DOTA avid lesion in the right foot. Following surgical excision of the tumour, there was significant relief in symptoms and gradual recovery of phosphate to normal levels. It is relevant and important for family physicians as in subjects with symptom like polyarthralgia, a simple measurement of analytes like phosphate, calcium and alkaline phosphatase in primary care setting will help to arrive at a cause and referral for further evaluation as this condition is potentially treatable.

Is hemi-thyroidectomy adequate in low risk differentiated thyroid cancer?

In low-risk differentiated thyroid carcinoma (LRDTC), appropriate surgical procedure in terms of hemi/total thyroidectomy (TT) has been an area of debate. The aim was to determine whether in LRDTC patients, hemithyroidectomy would be an adequate treatment, determine incidence of disease in contralateral lobe and evaluate the effect of radioactive iodine ablation (RAIA). Retrospective study was done from 2008 to 2014 at a single institution. Preoperative ultrasound (USG) and histopathology reports of all LRDTC patients following total/completion thyroidectomy were recorded. Details of postthyroidectomy, thyroid whole body scan, and stimulated serum thyroglobulin (sTg) levels were also documented and results analyzed. A total of 114/562 patients met inclusion criteria. Of these, 25/114 (22%) underwent hemithyroidectomy followed by a completion thyroidectomy while remaining 89/114 (78%) underwent TT initially. Preoperative USG detected single-lobe involvement in 44 patients; however, among them, histopathology revealed bilateral lobe disease in 17 (38.6%). There was a significant fall of sTg level following RAIA as compared to that before RAIA in T1b-T2 (P = 0.009 and 0.012, respectively). Median follow-up was 2 years (range: 1-7 years) with no distant metastasis or deaths recorded till 2017, except for one local recurrence 4 years after RAIA. In conclusion, the role of TT in LRDTC patients is important as 46% of patients were found to have tumor in contralateral lobe as well. Significant fall in sTg levels following RAIA justifies RAIA of remnant lobe even in LRDTC (T > 1a). It facilitates early detection of recurrence when sTg alone is used for follow-up.

Outcome of Treatment for Medullary Thyroid Carcinoma-a Single Centre Experience.

We conducted this study to evaluate the demography, clinical presentation, management and outcomes of medullary thyroid carcinoma (MTC) from the Indian context. This was a retrospective study of patients with MTC managed between January 2008 and December 2016. All pertinent data was collected and the results were analysed using STATA (v.13.1). MTC accounted for 90/2022 (4.45%) patients managed with thyroid cancer during the study period. The mean age of presentation was 40 years (range 14-70 years) with 47 males and 43 females. The most common presentation included goitre with cervical lymphadenopathy seen in 60 patients (66.7%). There were 11 patients (12.2%) with systemic metastasis at presentation. Rearranged during transfection (RET) testing was performed in 71 patients and was positive in 25 (35.2%). The mutations among these patients were seen in the following codons: 634 (12), 804 (8), 790 (3) and 618 (2). Persistent hypercalcitoninemia (calcitonin > 50 pg/ml) was observed in 62/80 (77.5%) patients. Forty patients underwent a meta-iodo-benzyl-guanidine (MIBG) scan in the postoperative period, 10 were positive. The mean duration of follow-up was 32 months and 10 patients defaulted from follow-up. Sixteen patients developed metastasis during the period of follow-up while eight patients expired. The mean survival was 85.75 months (95% CI 78.7-92.7). MTC accounted for 4.5% of thyroid carcinomas in this cohort among which 35% were hereditary. Persistent hypercalcitoninemia following surgery is seen in more than 70% of patients but this does not affect survival. RET screening should be performed for all patients with MTC as curative surgery can be offered for mutation positive offspring.

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.