Advanced and Metastatic Gastrointestinal Stromal Tumors Presenting With Surgical Emergencies Managed With Surgical Resection: A Case Series.

Advanced and metastatic gastrointestinal stromal tumors (GISTs) presenting with surgical emergencies are rare. Neoadjuvant imatinib being the treatment of choice for non-metastatic advanced disease with a proven role in downstaging the disease may not be feasible in patients presenting with bleeding and obstruction. We present a case series with retrospective analysis of a prospectively maintained database of patients with advanced and metastatic GISTs presenting with surgical emergencies. Clinical characteristics, imaging and endoscopic findings, surgical procedures, histological findings, and outcomes in these patients were studied. Four patients were included in this case series, with three males and one female (age range: 24-60 years). Two patients presented with melena; one with hemodynamic instability despite multiple blood transfusions underwent urgent exploratory laparotomy for bleeding gastric GIST, while the other underwent surgical exploration after careful evaluation given the recurrent, metastatic disease with a stable metabolic response on six months of imatinib. One patient with metastatic jejunal GIST who presented with an umbilical nodule and intestinal obstruction was given a trial of non-operative management for 72 hours, but due to non-resolution of obstruction, segmental jejunal en bloc resection with the dome of the urinary bladder with reconstruction and metastasectomy was needed. The patient with advanced gastric GIST who presented with gastric outlet obstruction was resuscitated, and an attempt of endoscopic naso-jejunal tube placement was tried, which failed, and exploration was needed. The mean length of hospital stay was 7.5 days. Histopathological examination confirmed GIST in all four patients with microscopic negative resection margins. All patients were started on imatinib with dose escalation to 800 mg in the patient with recurrent and metastatic disease; however, the patient with bleeding gastric GIST experienced severe adverse effects of imatinib and discontinued the drug shortly. All four patients are disease-free on follow-ups of 15 months, 48 months for the patient with advanced non-metastatic disease, and six and 24 months for the patients with metastatic disease. In the era of tyrosine kinase inhibitor (TKI) therapy for advanced and metastatic disease, upfront surgery is usually reserved for surgical emergencies only. Surgical resection, the cornerstone for the treatment of resectable GIST, may also be clinically relevant in metastatic settings, although it requires a careful and individualized approach.

Hepatic artery vasospasm masquerading as early hepatic artery thrombosis in progressive familial intrahepatic cholestasis 3: a case report.

Post-liver transplant (LT) hepatic artery vasospasm is a vascular complication that is not well recognized and its incidence is not known. As a possible sequela to vasospasm, hepatic artery thrombosis is the second major cause of allograft failure after primary nonfunction and its reported incidence is 2.9% in adults and 8.3% in pediatric LT. Lacuna in knowledge regarding early hepatic artery vasospasm post-LT makes it a difficult condition to diagnose and treat, as the initial ischemic insult on graft can have devastating consequences. We report a case of pediatric progressive familial intrahepatic cholestasis type 3-related chronic liver disease who underwent cadaveric orthotopic LT and postoperatively developed fever, worsening hypotension, and elevated liver enzymes with an absence of arterial flow in intrahepatic branches on Doppler ultrasound. Suspecting early hepatic artery thrombosis, the patient was re-explored and the graft hepatic artery was found to be in a state of vasospasm. Following the infusion of intra-arterial papaverine, urokinase, and intravenous nicorandil, there was an improvement in blood flow. The patient responded well and was discharged on postoperative day 23 with normal liver enzymes.

Assessment of left ventricular dysfunction by strain echo in primary hyperparathyroidism and its reversal after parathyroidectomy.

BACKGROUND: Strain echocardiography is a highly sensitive modality for detecting myocardial disease at an early stage. Therefore, we aim to evaluate subclinical left ventricular dysfunction in primary hyperparathyroidism (PHPT) patients with myocardial strain imaging in addition to conventional echocardiography and to look for its reversal after parathyroidectomy (PTx). METHODS: Thirty patients who underwent curative parathyroidectomy for PHPT were included. All patients were evaluated with M mode echo, 2D echo and strain imaging before and 6 months after PTx. Left ventricular ejection fraction, left ventricular diastolic dysfunction, left ventricular hypertrophy (LVH), Global Longitudinal Strain (GLS) and global circumferential strain (GCS) were recorded. RESULTS: On M mode echo, LVH was present in 15 patients and 8 of them improved completely after PTx (p < 0.038). Incidence of systolic and diastolic dysfunction on 2D echo was 10% and 13.3% respectively; while myocardial strain imaging showed impaired systolic function in 46.7% patients. Hence, compared to conventional 2D echo, strain imaging showed 36.7% high detection rate of subnormal cardiac function. There was improvement in left ventricle dysfunction (p = 0.083), GLS and GCS (p = 0.034) after PTx. Serum parathormone demonstrated a strong positive correlation with change in GLS and GCS (p = 0.013, p = 0.126) while serum calcium showed a weak correlation with change in GLS and GCS following surgery. CONCLUSION: Myocardial strain imaging should be considered for all PHPT patients as early identification of subclinical ventricle dysfunction provides an opportunity for an early intervention and thereby preventing development of irreversible LV dysfunction.

Effect of Preoperative Carbohydrate Drink and Postoperative Chewing Gum on Postoperative Nausea and Vomiting in Patients Undergoing Day Care Laparoscopic Cholecystectomy: A Randomized Controlled Trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) causes an unexpected prolonged hospital stay after ambulatory surgery. Novel measures such as preoperative loading of oral carbohydrates and postoperative chewing gum have recently gained momentum for postoperative recovery. This study evaluated the effects of preoperative carbohydrate loading and postoperative chewing gum (CG) on PONV after daycare laparoscopic cholecystectomy (LC). METHODS: A total of 100 patients were randomized to group A (preoperative carbohydrate loading with 200 ml of water with 25 g of carbohydrate and postoperative chewing gum (CG) when the patient responded to his/her name) and group B (standard care). The incidence of PONV and pain was assessed by using visual analogue scale. Quality of recovery (QoR-15) was assessed by using QoR15 questionnaire at 6 h, 24 h and 48 h after surgery. RESULTS: The incidence of PONV and pain was lower in group A; however, it was not significant (p > 0.05). The severity of PONV, pain and the need for rescue antiemetic was significantly lower in group A (p < 0.05). The episodes of PONV and required dose of antiemetic were less in group A. Group A also had a significantly higher QoR-15 score at all time points (p < 0.001). Preoperative dyspepsia was also noticed as a significant confounding predictor for postoperative vomiting. CONCLUSION: Preoperative carbohydrate drinks and early postoperative CG reduces the severity of PONV and requirement of antiemetics in patients undergoing LC. Hence, these simple measures can be used as a standard of care to optimize perioperative care in patients undergoing daycare surgery.

Outcomes of open revascularization for chronic mesenteric ischemia at a tertiary care center in India.

OBJECTIVE: Chronic mesenteric ischemia (CMI) is a rare, debilitating disease associated with higher morbidity and mortality if not treated on time. In the past two decades, there has been a paradigm shift in its management with endovascular modality due to reduced perioperative morbidity and mortality. In the endovascular era, only a few patients require surgical therapy. We conducted this study to report our experience with open surgical revascularization at our hospital. METHODS: We have conducted a retrospective study after obtaining approval from Institutional Ethics Committee. Data regarding patients who underwent open revascularization for CMI with long-segment occlusion from 2016 to 2021 has been retrieved from the institutional database. The demographic data, clinical presentation, type of surgery and graft used, perioperative mortality and morbidity and length of hospital stay were evaluated. Overall survival and disease-free survival were assessed using Kaplan-Meier analysis. RESULTS: Twenty-one patients underwent open surgical revascularization; 16 were males and five females. The median age was 43 years. Fourteen (66.7%) were smokers. The mean duration of follow-up was 28.4 ± 13.6 months. Thirty-day postoperative mortality was 0% and morbidity was 28%. The average duration of hospital stay and postoperative weight gain were 6.9 ± 3.7 days and 11 ± 4.9 kgs, respectively. One patient died at two years of follow-up due to myocardial infarction and one had a recurrence. Long-term survival at 60 months of follow-up was 91.6% and the primary-patency rate was 95.2%. CONCLUSION: Owing to better long-term and reintervention-free patency, open revascularization should be considered in patients who are fit for surgery, particularly in patients with long-segment mesenteric artery occlusion.

Establishment and characterization of long-term human primary parathyroid tumor subclones derived from Indian PHPT.

The continuous cell line of epithelial human parathyroid cells has been proven difficult. Previously, PTH-C1 cell line was only established rat parathyroid tissue cell line known to express the parathyroid hormone-related peptide (Pthrp) gene. The paucity of continuous cell line of human parathyroid cells secreting parathyroid hormone (PTH) has imposed hurdle in in vitro assessment of the mechanisms involved in the control of parathyroid cell function and proliferation. The primary cell cultures of human parathyroid cells were derived from parathyroid adenoma tissue biopsy (n = 5). The cells were subsequently subcultured to maintained primary subclones. Karyotyping analysis was performed to analyze the genotypic identity of derived subclones. The expression of calcium-sensing receptor (CaSR) and intact parathyroid hormone (iPTH) were analyzed using immunocytochemistry and immunofluorescence. In the present study, we have used a defined condition medium to generate the continuous culture of human parathyroid cells derived from patients with parathyroid adenoma due to primary hyperparathyroidism. The subcultured primary subclones were maintained epithelial and polygonal morphology, doubling time of approximately 25 h, displaying a diploid chromosome number, and secretion of PTH. This cell line produces PTH and expresses the calcium-sensing receptor (CaSR) known to be involved in parathyroid function. Altogether these findings indicate the uniqueness of the human parathyroid cell line as an in vitro model for cellular and molecular studies on parathyroid physiopathology.

Visceral Obesity as a Predictor of Postoperative Complications After Pancreaticoduodenectomy.

INTRODUCTION: Obesity is associated with increased morbidity and mortality post surgery. The measurement of visceral obesity can predict postoperative outcomes after pancreaticoduodenectomy. METHODS: This is a prospective observational study. Visceral obesity was calculated by measuring the fat thickness in the retro-renal area by using a computed tomography scan. Visceral obesity was defined as retro-renal fat thickness (RRFT) of ≥ 2 cm. Patients were divided into two groups: Group-A (RRFT < 2 cm, non-obese) and Group-B (RRFT > 2 cm, obese). Demographic, clinical, and intraoperative variables were correlated with postoperative outcomes. RESULTS: Fifty-six patients were included in the study. Thirty-two patients were included in Group-A, and 24 patients were included in Group-B. The two groups had comparable outcomes. A total of 21 patients in Group-A (65.62%) and 17 patients in Group-B (70.83%) had comorbidities, including diabetes mellitus, hypertension, and coronary disease (p=0.680). American Society of Anesthesiologists (ASA) grading was comparable (p=0.927). BMI was also comparable (p=0.354). Type of pancreaticoduodenectomy, pancreatic texture, pancreatic duct diameter, and technique of pancreaticojejunostomy anastomosis were comparable. The mean operative time was longer in Group-B (362 ± 36.2 min vs. 298 ± 45.2 min) (p=0.001). Intraoperative blood loss was more in Group-B (312 ± 36.8 ml vs. 267 ± 23.7 ml) (p=0.001). The rates of postoperative pancreatic fistula and delayed gastric emptying were comparable (p=0.402 and p=0.134, respectively). The length of hospital stay was longer in patients in Group-B (p=0.004). There was one death in Group-B (obese group). CONCLUSION: Visceral obesity is a risk factor for postoperative complications after a pancreaticoduodenectomy.

Treatment outcomes of adjuvant radiotherapy in adrenocortical carcinoma - A 13-years experience from a tertiary care centre.

Purpose: Adrenocortical carcinoma (ACC) is a rare and highly aggressive malignant neoplasm, usually diagnosed in advanced stage. Role and efficacy of adjuvant radiotherapy has not been well defined. The objective of this study is to describe the various clinical characteristics and prognostic factors affecting the survival of ACC along with the role radiotherapy on overall survival and relapse free survival. Methods: A retrospective analysis of 30 patients registered between 2007 and 2019 was carried out. The medical records containing clinical and treatment details were analysed. Data was analysed using SPSS 25.0. Survival curves were computed using Kaplan-Meier method. Univariate and multivariate analyses were performed to analyze the prognostic factors affecting the outcome. A p value of less than 0.05 was considered to be statistically significant. Results: The median age of patients was 37.5 years (range, 5-72 years). 20 patients were females. Twenty-six patients had advanced stage (III/IV) disease while only four patients presented in early stage. Twenty-six patients underwent total adrenalectomy. Eighty three percent patients received adjuvant radiation therapy. The median follow up was 35.5 months (range, 7 monthss-132months). The estimated three- and 5-years overall survival (OS) was 67.2% and 23.3%, respectively. Capsular invasion and positive margins were the independent prognostic factors influencing both OS and relapse free survival (RFS). Out of 25 patients who received adjuvant radiation, only three patients had local relapse. Conclusion: ACC is a rare and aggressive neoplasm with majority of patients presenting in advanced stage. Surgical resection with negative margins remains the mainstay of treatment. Capsular invasion and positive margins are independent prognostic factors for survival. Adjuvant radiation reduces the risk of local relapse and is well tolerated. Radiation can be used effectively in adjuvant and palliative settings in ACC.

Cytomorphologic and immunocytochemical diagnosis of primary hepatic angiosarcoma in a young adult: Challenging diagnosis of a rare, aggressive malignancy.

Primary hepatic angiosarcoma (PHA) is a rare, rapidly growing, highly aggressive hepatic malignancy, primarily seen in elderly males. Establishing an accurate clinical diagnosis is challenging owing to its rarity and nonspecific presentation. Rendering a cytologic diagnosis of PHA is extremely difficult, and immunocytochemistry(ICC) on cell block(CB) sections is essential to confirm the diagnosis. The characteristic cytomorphologic features of PHA have rarely been documented, further augmenting the diagnostic challenge. A 32-year-old male presented with abdominal pain, abdominal distension, and significant weight loss over the past 9 months. On examination, the abdomen was distended, with multiple spider angiomas and a large mass in the right hypochondrium. His renal function tests, liver function tests, and serum tumor markers were within normal limits. An abdominal triphasic computerized tomography revealed a large lobulated mass in the right lobe with central necrosis. An ultrasound-guided FNA was performed from the liver lesion. The cytologic smears showed singly scattered large, markedly pleomorphic, epithelioid-elongated tumor cells having oval-elongated nuclei, irregular nuclear contours, coarse chromatin, prominent macronucleoli, and abundant finely vacuolated cytoplasm in a background of blood. ICC on the CB demonstrated diffuse positivity for vimentin, CD31, and nuclear positivity for FLI-1, confirming a vascular origin. Hence, a final cytologic diagnosis of primary hepatic angiosarcoma was rendered. The index report describes the characteristic cytomorphologic and immunocytochemical features of a rare hepatic malignancy in a young male and reiterates the usefulness of FNAC coupled with CB-ICC in the quick and precise diagnosis of such challenging cases.

Multilevel Annotation of Germline MEN1 Variants of Synonymous, Nonsynonymous, and Uncertain Significance in Indian Patients With Sporadic Primary Hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is third most common endocrine disorder characterized by hypercalcemia with elevated or nonsuppressed parathyroid hormone levels by parathyroid tumors. Familial PHPT, as part of multiple endocrine type-1, occurs due to the germline mutation in the MEN1 gene. The involvement and the role of germline MEN1 variations in sporadic PHPT of Indian PHPT patients are unknown. Precise classifications of different types of MEN1 variations are fundamental for determining clinical relevance and diagnostic role. This prospective cohort study was performed on 82 patients with PHPT (with no clinical or history of MEN1) who underwent screening for MEN1 variations through Sanger sequencing. Multilevel computational analysis was performed to determine the structure-function relationship of synonymous, nonsynonymous, and variants of uncertain significance (VUS). Of the 82 PHPT patients, 42 (51%) had 26 germline MEN1 variants, including eight nonsynonymous, seven synonymous, nine VUS, one splice site, and one regulatory variation. Five most common germline variations (c.1838A>G, c.1817C>T, c.1525C>A, c.-35A>T, and c.250T>C) were observed in this study. c.-35A>T (5' untranslated region [UTR]) was associated with recurrence of PHPT (odds ratio [OR] = 5.4; p = 0.04) and subsequent detection of other endocrine tumors (OR = 13.6, p = 0.035). c.1525C>A was associated with multi glandular parathyroid tumor (OR = 13.6, p = 0.035). Align-Grantham variation and Grantham deviation (Align-GVGD), functional analysis through hidden Markov MODEL (FATHMM), and MutationTaster analysis reported the disease-specific potential of VUS and synonymous variations. Significant linkage disequilibrium was observed in c.1785G>A and c.1817C>T (r2  = 0.3859, p = 0.0001), c.1475C>G and c.1525C>A (r2  = 0.385, p = 0.0004), and c.1569T>C and c.1838A>G (r2  = 0.488, p = 0.0001). The detection of MEN1 variations, especially those with disease-specific potential, can prompt early screening for other MEN1-related tumors and disease recurrence. © 2022 American Society for Bone and Mineral Research (ASBMR).

Replaced Right Hepatic Artery Arising From the Celiac Trunk: A Rare and Challenging Anatomical Variant of the Pancreaticoduodenectomy Procedure.

Anatomic variation of the hepatic artery is common and often seen in patients with periampullary carcinoma undergoing a pancreatic duodenectomy. Replaced right hepatic artery from the superior mesenteric artery is the most common variant encountered. Here we present a rare case of an unclassified pattern of the variant anatomy of replaced right hepatic artery originating from the celiac trunk along with an accessory left hepatic artery arising from the left gastric artery in a patient with periampullary carcinoma undergoing pancreaticoduodenectomy.

Baseline renal dysfunction determines mortality following parathyroidectomy in primary hyperparathyroidism: analysis of Indian PHPT registry.

INTRODUCTION: Primary hyperparathyroidism (PHPT) in India is mostly symptomatic with renal and skeletal complications. Evidence on mortality outcomes following parathyroidectomy from India, where the disease is predominantly symptomatic is limited. MATERIAL AND METHODS: This was a prospective study to evaluate mortality outcomes in the Indian PHPT registry over the past 25 years (n = 464). Pre- and postoperative parameters and mortality data were obtained from medical records and/or by verbal autopsy, a method validated by WHO for data collection in settings where several deaths are noninstitutional. Patients were divided into survivor (SG) and nonsurvivor groups (NSG) to ascertain differences in presentation and the effect of parathyroidectomy. RESULTS: The overall mortality was 8.8% at a median follow-up of 8 years (IQR 1-13) after parathyroidectomy. Chronic kidney disease was the most common background cause of death (43.5%), followed by pancreatitis (28.2%). NSG had significantly more frequent renal dysfunction (91.9% vs 73.9%), anaemia (50 vs 16.6%) and pancreatitis (24.3 vs 6.4%). PTH (61.9 vs 38.3 pmol/l) and baseline creatinine (97.2 vs 70.7 µmol/l) were significantly higher and eGFR lower (66.7 vs 90.7 ml/min/1.73m2) in the NSG than SG. By Cox proportional modelling, renal dysfunction [HR 2.88 (1.42-5.84)], anaemia [HR 2.45 (1.11-5.42)] and pancreatitis [HR 2.65 (1.24-5.66)] on univariate and renal dysfunction [HR 3.33 (1.13-9.77)] on multivariate analysis were significant for mortality. Survival curves demonstrated a significantly higher mortality with lower eGFR values. CONCLUSIONS: Nonsurvivors in PHPT had greater prevalence and more severe baseline renal dysfunction than survivors. Survival after parathyroidectomy was significantly associated with estimated glomerular filtration rate at baseline.

Experience With Changing Etiology and Nontransplant Curative Treatment Modalities for Hepatocellular Carcinoma in a Real-Life Setting-A Retrospective Descriptive Analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) has variable etiological risk factors. Radiofrequency ablation (RFA) and surgical resection (SR) are frequently used as curative treatment options. In the present study, we assessed the etiological factors and efficacy of RFA and SR in patients with unifocal HCC in a real-life setting. METHODS: Of 870 patients with HCC seen over a period of nine years, 785 patients were assessed for stage and etiological risk factors. Of these, 110 (14%) patients with single HCC who were either treated with RFA (n = 72) or SR (n = 38) were evaluated for their outcomes in terms of overall survival (OS) and disease-free survival (DFS) over 3 years. RESULTS: Of 785 patients [median age 60 (range 51-65) years, males (n = 685, 87.3%)] with HCC, viral hepatitis [HBV and HCV with or without alcohol = 502 (63.9%)] was the most common etiology; nonalcoholic steatohepatitis (NASH) and alcohol as an etiology showed increase over the years. About 677 (86.2%) patients had evidence of cirrhosis; NASH and HBV were predominant causes in noncirrhotic patients. Even though the groups were not matched, in 110 patients subjected to either RFA [mean tumor size, 2.2 (1.9-2.8) cm] or SR [mean tumor size, 7.1 (4.8-9.7) cm], tumor progression was observed in 49 (68%) and 16 (42%) patients in RFA and SR groups, respectively, with superior DFS in the SR group (P < 0.01). Of total 31 deaths, 20 (27.8%) deaths were in the RFA group and 11 (28.9%) in the SR group with no difference in OS at 3 years. CONCLUSION: Viral hepatitis with or without alcohol is the commonest etiological factor for HCC in Northern India; NASH and alcohol are increasing over the years. In a real-life setting, in patients with unifocal HCC, there is no difference in overall 3-year survival subjected to SR or RFA with better DFS in the SR group.

Rare case of concomitant juxtarenal aortic aneurysm and type 1 Inferior Vena Cava duplication: -intraoperative challenges to avoid catastrophe.

Duplication of the inferior vena cava is a rare congenital anomaly, with an incidence of 0.2-3%. Despite being asymptomatic, anomalies of IVC are important in aortoiliac and retroperitoneal surgeries. Preoperative CT imaging is essential to identify any IVC anomaly and to prevent unexpected hemorrhage during surgery. Here, we report a case of a juxtarenal abdominal aortic aneurysm in which we encountered a type I IVC duplication anomaly intraoperatively while performing transperitoneal aneurysmorrhaphy and took precautions to avoid any iatrogenic injuries to either of the two trunks or the pre-aortic trunk of the anomalous duplicate IVC.

A duplicação da veia cava inferior (VCI) é uma anomalia congênita rara com incidência de 0,2 a 3%. Apesar de assintomáticas, anomalias da VCI são importantes em cirurgias aortoilíacas e retroperitoneais. A imagem da tomografia pré-operatória é essencial para identificar qualquer anomalia de VCI e para evitar hemorragia inesperada durante a cirurgia. Relatamos um caso de aneurisma de aorta abdominal justarrenal, no qual encontramos uma anomalia de duplicação de VCI do tipo 1 intraoperatório enquanto realizávamos correção cirúrgica de aneurisma transperitoneal. Por isso, tomamos a precaução para evitar qualquer lesão iatrogênica nos dois troncos e no tronco pré-aórtico de VCI duplicada anômala.

Demographic Patterns, Risk Factors, and Outcomes of Abdominal Aortic Aneurysms in Young Adults ≤55 Years: An Experience in a Tertiary Care Centre of India.

Introduction Abdominal aortic aneurysms (AAA) are uncommon in young adults ≤55 years of age. There is a lack of literature on clinical characteristics, risk factors, and therapeutic outcomes so we present a case series of 11 patients of AAA aged ≤55 years. Methods We included single-center retrospective case series between 2013 to 2020. We reviewed 44 patients who were operated for AAA in a tertiary care center in India. We identified 13 patients who were ≤55 years; two patients with incomplete records were excluded. A patient information sheet was used to retrieve demographic data, clinical presentation, outcomes, and follow-up. Results Out of 11 patients, 10 were men. Nine patients (81.8%) had symptomatic AAA. The majority (45.4%) exhibited an infrarenal aneurysm and the median size of the aneurysm was 5.8 cm (IQR: 5.5-6.4 cm). Eight patients (72.7%) had a history of smoking. Hypertension was observed in six patients and one patient had associated coronary artery disease. Clamping time was > 45 minutes among three patients; all smokers. Blood loss was > 500 ml in five patients. The median length of hospital stay was 10 days (7-40); more among patients with metabolic equivalents (METS) score < 4, 14.5 (8-19) days. No grade III-IV complications and mortality were noted with a median follow-up of 15 months, with all patients living. Conclusion The aneurysm was symptomatic in the majority of participants. An association of smoking in increasing both the median clamping time and length of hospital stay was seen. No mortality and good disease-free follow-up suggested good outcomes.

Surgical outcome after focused parathyroidectomy: experience from a tertiary care centre in North India.

<b style="color: #075541"> Introduction:</b> Focused parathyroidectomy is the gold standard treatment for primary hyperparathyroidism (PHPT) due to single gland disease with a comparable success rate as that of conventional four gland exploration. It is also associated with fewer surgical complications. Despite these benefits, there is still controversy about the high recurrence following the focused approach. </br> </br> <b style="color: #075541">Aim:</b> The aim was to analyse our experience regarding the success rate of focused parathyroidectomy for PHPT. </br> </br> <b style="color: #075541">Methods:</b> This was a retrospective analysis of 192 patients of PHPT between January 2017 and August 2020 who underwent focused parathyroidectomy without intraoperative parathormone analysis, and had a minimum follow up of six months. Demographic profile, biochemical (pre and postoperative), radiological, operative and histological detail of all patients were recorded. Parathyroidectomy was considered curative if the patient maintained normal serum calcium and parathormone (PTH) levels six months after surgery. Persistent hyperparathyroidism was considered if hypercalcemia or high PTH levels persisted, or recurrent disease when a patient had rising serum calcium and / or PTH levels six months after curative parathyroidectomy. </br> </br> <b style="color: #075541">Results:</b> No patient had pain and wound-related complications after parathyroidectomy. Two patients had voice change in the immediate postoperative period which recovered subsequently; no patient had documented vocal cord paralysis. The persistent disease was present in two patients; both required neck exploration. Five patients had recurrence of PHPT within six months of parathyroidectomy; all of them had hyperplasia on the final biopsy. The overall cure rate was 97.92%. </br> </br> <b style="color: #075541">Conclusion:</b> Therefore, we propose focused surgery for sporadic PHPT should be considered as a preferred treatment with acceptable recurrence rate and surgical complications.</br> </br> <b style="color: #075541">KEYWORDS:</b>focused parathyroidectomy, parathyroidectomy, primary hyperparathyroidism.

GCM2 Silencing in Parathyroid Adenoma Is Associated With Promoter Hypermethylation and Gain of Methylation on Histone 3.

CONTEXT: Glial cells missing 2 (GCM2), a zinc finger-transcription factor, is essentially required for the development of the parathyroid glands. OBJECTIVE: We sought to identify whether the epigenetic alterations in GCM2 transcription are involved in the pathogenesis of sporadic parathyroid adenoma. In addition, we examined the association between promoter methylation and histone modifications with disease indices. METHODS: Messenger RNA (mRNA) and protein expression of GCM2 were analyzed by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry in 33 adenomatous and 10 control parathyroid tissues. DNA methylation and histone methylation/acetylation of the GCM2 promoter were measured by bisulfite sequencing and chromatin immunoprecipitation-qPCR. Additionally, we investigated the role of epigenetic modifications on GCM2 and DNA methyltransferase 1 (DNMT1) expression in parathyroid (PTH)-C1 cells by treating with 5-aza-2'-deoxycytidine (DAC) and BRD4770 and assessed for GCM2 mRNA and DNMT1 protein levels. RESULTS: mRNA and protein expression of GCM2 were lower in sporadic adenomatous than in control parathyroid tissues. This reduction correlated with hypermethylation (P < .001) and higher H3K9me3 levels in the GCM2 promoter (P < .04) in adenomas. In PTH-C1 cells, DAC treatment resulted in increased GCM2 transcription and decreased DNMT1 protein expression, while cells treated with the BRD4770 showed reduced H3K9me3 levels but a nonsignificant change in GCM2 transcription. CONCLUSION: These findings suggest the concurrent association of promoter hypermethylation and higher H3K9me3 with the repression of GCM2 expression in parathyroid adenomas. Treatment with DAC restored GCM2 expression in PTH-C1 cells. Our results showed a possible epigenetic landscape in the tumorigenesis of parathyroid adenoma and also that DAC may be a promising avenue of research for parathyroid adenoma therapeutics.