Nearly Half of Patients with Anaplastic Thyroid Cancer May Be Amenable to Immunotherapy.

IMPORTANCE: Poorly differentiated cancer (PDC) and anaplastic thyroid cancer (ATC) have an aggressive course of disease with limited treatment options. The expression of programmed cell death ligand-1 (PD-L1) has been used to determine the responses of many cancers to immunotherapy. The aim of the study was to investigate the expression of PD-L1 in a cohort of patients with PDC and ATC to assess their suitability for immunotherapy. Data, settings, and participants: This study is a retrospective cohort review of patients treated for PDC and ATC treated at a tertiary referral institution during the period 2000-2020. PD-L1 22C3 pharmDx qualitative immunohistochemistry was performed on formalin-fixed, paraffin-embedded (FFPE) specimens of tumours to detect the presence of the PD-L1 protein. MAIN OUTCOME MEASURES: The percentage of tumours that were positive for PD-L1 immunohistochemistry and the PD-L1 protein expression as measured by using the Tumour Proportion Score (TPS). Secondary outcomes studied were the associations between demographic, clinicopathological, treatment and disease outcomes and PD-L1 expression. RESULTS: Nineteen patients (12F:7M) with a mean age of 65.4 (±14.3 SD) years were diagnosed with PDC in 4 (21%) and fifteen were diagnosed with ATC (79%) during the study period. Fifteen (79%) patients underwent some form of surgery, with R0 resection achieved in only three of the fifteen (20%) patients. Overall, PD-L1 expression was seen in seven of the fifteen (47%) of the patients with ATC, with no positivity seen in the patients with PDC. PD-L1 expression had no impact on treatment modality and positive expression was not significantly associated with stage of disease, metastasis, or survival. CONCLUSION: Nearly half of patients with ATC express PD-L1 and may be amenable to immunotherapy with pembrolizumab.

Challenges in genetic screening for inherited endocrinopathy affecting the thyroid, parathyroid and adrenal glands in Singapore.

Significant progress has been made in the understand-ing of many human diseases, especially cancers, which has contributed to improved and increased survival. The Human Genome Project and The Cancer Genome Atlas project brought about a new era, with an understanding of inherited diseases at a molecular level, which subsequently facilitated the option of precision medicine. Precision medicine has helped tailor treatment decisions at an individual level, for instance in terms of surgical treatments or targeted therapies in advanced diseases. Despite the increasing advances in genetic-lead precision medicine, this has not translated into increasing uptake among patients. Reasons for this may be potential knowledge gaps among clinicians; on reasons for poor uptake of genetic testing such as for cultural, religious or personal beliefs; and on financial implications such as lack of support from insurance companies. In this review, we look at the current scenario of genetic screening for common inherited endocrine conditions affecting the thyroid, parathyroid and adrenal glands in Singapore, and the implications associated with it.

Performance of a multigene genomic classifier and clinical parameters in predicting malignancy in a Southeast Asian cohort of patients with cytologically indeterminate thyroid nodules.

BACKGROUND: Most thyroid nodules are benign. It is important to determine the likelihood of malignancy in such nodules to avoid unnecessary surgery. The primary objective of this study was to characterize the genetic landscape and the performance of a multigene genomic classifier in fine-needle aspiration (FNA) biopsies of cytologically indeterminate thyroid nodules in a Southeast Asian cohort. The secondary objective was to assess the predictive contribution of clinical characteristics to thyroid malignancy. METHODS: This prospective, multicenter, blinded study included 132 patients with 134 nodules. Molecular testing (MT) with ThyroSeq v3 was performed on clinical or ex-vivo FNA samples. Centralized pathology review also was performed. RESULTS: Of 134 nodules, consisting of 61% Bethesda category III, 20% category IV, and 19% category V cytology, and 56% were histologically malignant. ThyroSeq yielded negative results in 37.3% of all FNA samples and in 42% of Bethesda category III-IV cytology nodules. Most positive samples had RAS-like (41.7%), followed by BRAF-like (22.6%), and high-risk (17.9%) alterations. Compared with North American patients, the authors observed a higher proportion of RAS-like mutations, specifically NRAS, in Bethesda categories III and IV and more BRAF-like mutations in Bethesda category III. The test had sensitivity, specificity, negative predictive value, and positive predictive value of 89.6%, 73.7%, 84.0%, and 82.1%, respectively. The risk of malignancy was predicted by positive MT and high-suspicion ultrasound characteristics according to American Thyroid Association criteria. CONCLUSIONS: Even in the current Southeast Asian cohort with nodules that had a high pretest cancer probability, MT could lead to potential avoidance of diagnostic surgery in 42% of patients with Bethesda category III-IV nodules. MT positivity was a stronger predictor of malignancy than clinical parameters.

A Case of Parathyroid Carcinoma in Renal Hyperparathyroidism.

Introduction: Parathyroid carcinoma is a rare malignant endocrine tumor that is usually associated with primary hyperparathyroidism. The coexistence of parathyroid carcinoma and renal hyperparathyroidism is a rare phenomenon. Hence, we present a case of parathyroid carcinoma in a patient with tertiary hyperparathyroidism. Case Presentation: Our patient is a 31-year-old woman with a past medical history of end-stage renal failure (ESRF), on hemodialysis for the past 18 years. She was referred by her nephrologist to the endocrine surgery department for consideration of parathyroidectomy in view of long-standing tertiary hyperparathyroidism complicated by hypercalcemia. Bedside ultrasonography scan (US) of the thyroid revealed three parathyroid glands and a hypoechoic right lower pole thyroid nodule with central calcification. Fine-needle aspiration cytology was performed for the suspected thyroid nodule on the same day, which eventually yielded a follicular lesion of undetermined significance. A right hemithyroidectomy and total parathyroidectomy with deltoid implantation was performed. Intraoperative exploration revealed that the thyroid nodule noted at initial US was found to be the right superior parathyroid gland invading into the right thyroid itself. The right superior parathyroid gland was excised en bloc with the right hemithyroidectomy. Post-operatively, the patient was hypocalcemic but was discharged well on post-operative day 5. Histopathological diagnosis of the right hemithyroidectomy specimen containing the right superior parathyroid gland was consistent with that of parathyroid carcinoma. Conclusion: Parathyroid carcinoma is a rare entity that is difficult to diagnose. In patients with ESRF, the presence of concurrent tertiary hyperparathyroidism makes this even more challenging.

Role of Truncated O-GalNAc Glycans in Cancer Progression and Metastasis in Endocrine Cancers.

Glycans are an essential part of cells, playing a fundamental role in many pathophysiological processes such as cell differentiation, adhesion, motility, signal transduction, host-pathogen interactions, tumour cell invasion, and metastasis development. These glycans are also able to exert control over the changes in tumour immunogenicity, interfering with tumour-editing events and leading to immune-resistant cancer cells. The incomplete synthesis of O-glycans or the formation of truncated glycans such as the Tn-antigen (Thomsen nouveau; GalNAcα- Ser/Thr), its sialylated version the STn-antigen (sialyl-Tn; Neu5Acα2-6GalNAcα-Ser/Thr) and the elongated T-antigen (Thomsen-Friedenreich; Galß1-3GalNAcα-Ser/Thr) has been shown to be associated with tumour progression and metastatic state in many human cancers. Prognosis in various human cancers is significantly poor when they dedifferentiate or metastasise. Recent studies in glycobiology have shown truncated O-glycans to be a hallmark of cancer cells, and when expressed, increase the oncogenicity by promoting dedifferentiation, risk of metastasis by impaired adhesion (mediated by selectins and integrins), and resistance to immunological killing by NK cells. Insight into these truncated glycans provides a complimentary and attractive route for cancer antigen discovery. The recent emergence of immunotherapies against cancers is predicted to harness the potential of using such agents against cancer-associated truncated glycans. In this review, we explore the role of truncated O-glycans in cancer progression and metastasis along with some recent studies on the role of O-glycans in endocrine cancers affecting the thyroid and adrenal gland.

Reduced uptake pattern on 68 Ga-DOTATATE-scan may indicate necrosis predicting aggressive behavior in pheochromocytoma and paragangliomas (PPGLs).

BACKGROUND: Predicting malignancy among pheochromocytoma paragangliomas (PPGLs) remains a challenge, with only limited understanding of the clinical and molecular characteristics. It has been suggested that reduced avidity of a PPGL on 68 Ga-DOTATATE PET/CT could be a sign of not only altered metabolic activity, but also of increased biologic aggressiveness, possibly due to loss of SSTR-expression. DESIGN: Retrospective cohort review. PATIENTS AND MEASUREMENTS: Thirty-seven patients who underwent treatment for PPGL at a tertiary institution over the period 2010-2022, had their biochemical, radiological, and clinicopathological variables collected. RESULTS: Five of 37 (13%) patients (5 males) with a mean age of 42 years were found to have malignant PPGLs. The mean size of the tumors were 5.4 cm, with 4 located in the paraaortic area and 1 in right adrenal. Functional imaging with 68 Ga-DOTATATE PET/CT showed a mean SUVmax of 4.5. Four of 5 patients underwent open resection of the tumors under general anesthesia following preoperative alpha blockade with oral phenoxybenzamine. The mean PASS score of the excised tumors was 5.5 in keeping with biologically aggressive tumors, with evidence of necrosis. All but 1 patient had germline SDHB-mutation (Deletion Exon 1). Postintervention after a mean follow-up of 31 months, 2 of 5 (40%) patient developed spinal metastasis and 1 patients (25%) died of cardiac complications. CONCLUSION: A non-highly avid PPGL on DOTATE scan should be considered as possibly having necrosis of tumors indicating a more aggressive tumor-biology. There might be a subgroup of patients in whom FDG-PET scan should be considered to gain additional information.

Variant anatomy of non-recurrent laryngeal nerve: when and how should it be taught in surgical residency?

INTRODUCTION: While the performance of a thyroidectomy is generally associated with a low risk of injury to the recurrent laryngeal nerve (RLN), the presence of a non-recurrent nerve (NRLN) increases the risk of this complication. Generally, the intraoperative detection via visual appreciation of variant anatomy of the RLN has been regarded as poor, possibly due to a lack of knowledge of both the normal and aberrant anatomy of the RLN. MATERIALS AND METHODS: Articles for the review were searched through PubMed using the search terms and their combinations: "non-recurrent laryngeal nerve," "thyroidectomy," "injury," "palsy," "variant anatomy," and "residency," from January 1, 2000, to December 2022. Papers considered for the review were the articles published in English, with additional classic and articles of surgical importance retrieved from the reference list of papers. Only papers relevant to the scope of the review were considered for this review. FINDINGS: The NRLN has been found to be associated with concurrent vascular abnormalities, such as the presence of an aberrant right subclavian artery (ARSA) or an arteria lusoria originating from the aortic arch. However, it seems that both the normal as well as aberrant anatomy of the RLN is currently not emphasized enough during postgraduate surgical training. With the increased use of intraoperative neuromonitoring (IONM), detection of NRLN has become possible through appropriate neural mapping during thyroid surgery, besides other pointers such as visualization during surgery, computerised tomography, and duplex ultrasound scans to visualize the variant vascular anatomy. There is also a possible role for cadaveric courses, either during medical school or in a post-graduate setting-adapted to the student's level to teach the variant anatomy. With the development of newer techniques such as artificial intelligence, there are potential new options for teaching and training anatomy in the near future. CONCLUSIONS AND RELEVANCE: Adequate knowledge of the normal and aberrant anatomy of the RLN remains essential for the best outcomes in thyroid surgery, even in the era of the IONM. Moving forward, the knowledge of (aberrant) anatomy should be made an integral part of the core competencies of both medical students and surgical trainees. It is imperative that leaders of the different field work closely together to combine their knowledge towards providing their trainees with the best possible training options.

The efficacy of adjuvant radioactive iodine after reoperation in patients with persistent or recurrent differentiated thyroid cancer: a systematic review.

OBJECTIVE: The effectiveness of adjuvant radioiodine (RAI) after reoperation in patients with persistent or recurrent differentiated thyroid cancer (DTC) is controversial. Although various organizations recognize that strong evidence for the use of RAI is lacking, they continue to recommend the use of adjuvant RAI therapy for select groups of patients. This is concerning as RAI therapy has potential side effects such as gastrointestinal symptoms, bone marrow suppression, and gonadal damage. METHODS: Four electronic databases were systematically searched for randomized trials or observational studies that examined the outcomes of adjuvant RAI after reoperation for recurrent DTC, among patients of any age. The baseline characteristics, treatment response, disease progression, and overall survival of these studies were synthesized and reported. A meta-analysis of the use of RAI on progression-free survival was also performed. RESULTS: Six observational studies, comprising a combined cohort of 437 patients who underwent reoperation, were included from 1212 records. Adjuvant RAI after reoperation in recurrent DTC was not associated with longer progression-free or overall survival. There was also no association of RAI with excellent structural or biochemical treatment response, lower thyroglobulin levels, nor a lower rate of second recurrence or distant metastases. CONCLUSIONS: Adjuvant RAI after reoperation in recurrent DTC was not associated with improved cancer or treatment-related outcomes. However, as the included studies were of inadequate quality, there is an urgent need for randomized trials and well-analyzed cohort studies. Physicians should exercise clinical judgment to prescribe adjuvant RAI for only selected, high-risk patients.

Open versus laparoscopic intraperitoneal on-lay mesh repair: A comparison of outcomes in small ventral hernia.

PURPOSE: The ideal surgical treatment of small ventral hernias (defect less than 4 cm) is still debatable. In our study, we sought to compare the outcomes of open versus laparoscopic intraperitoneal on-lay mesh (IPOM) repair in small ventral hernias. METHODS: Patients with a single ventral hernia defect of less than 4 cm undergoing surgical mesh repair between January 2016 and September 2018 were prospectively registered for this study. The minimum follow-up duration was 12 months. Patient demographics, operative findings and regular post-operative follow-up details including recurrence rates and complications were recorded and analysed. RESULTS: 41 patients underwent laparoscopic IPOM repair and 47 patients underwent open IPOM repair. The mean age for both groups is similar with no significant difference. The mean hernia defect size for the laparoscopic group is 2.8 cm (±0.8) whereas the mean hernia defect size for the open repair group is 2.1 cm (±0.4). The mean surgery duration for open IPOM repair was significantly shorter (59 min (±17) vs 74 min (±26); p = 0.001). There was no significant difference in the incidence of seroma formation and surgical site infections post-operatively. There was also no significant difference in both groups in terms of chronic pain and recurrence at 1-year follow-up. CONCLUSION: Open IPOM repair for small ventral hernias may be superior to laparoscopic IPOM repair due to the shorter operative duration, single incision, and no additional risk of port-site hernias. There was no difference in chronic pain, wound infection and recurrence rate between the two groups.

The impact of value-driven outcomes initiative on endo-laparoscopic groin hernia repair.

PURPOSE: Value driven outcome (VDO) initiative is a value-based, patient-focused tool which utilizes a clinical outcome-based approach to optimize value of care based on clinically relevant quality indicators and costs required to achieve the care. In this study, we evaluate the impact of a VDO initiative on groin hernia repair, a commonly performed elective surgery in our hospital. METHODS: A VDO initiative was implemented in 2019 to encourage elective inguinal hernia repair to be performed at a day surgery setting. A comparison of outcomes was made between hernia surgeries performed in 2019 with those in 2020 and 2021. Pre-defined criteria were used to select patients that can be operated at a day surgery setting. Patients' expectations were addressed preoperatively about day surgery procedure and postoperative recovery. Day surgery bundles were used to standardize pre- and post-surgery protocols. Pain control was optimized using a specialized local anesthesia regime. RESULTS: A total of 263 laparoscopic hernia surgeries were performed between May 2019 and December 2021. After implementation of VDO initiative, the percentage of patients discharged within 24 h increased from 78% in year 2019 to 97% in year 2020 and 99% in year 2021. Conversion rate for day surgery to short stay decreased from 9% in year 2019 to 1% in year 2020 and 2% in year 2021. In 2019 to 2021, there were no 30-day readmission, no hernia recurrence in 90 days, no conversion to open surgery. CONCLUSION: VDO initiative is a promising tool to deliver better value-based care for patients undergoing endo-laparoscopic inguinal hernia repair.

A systematic cohort review of pheochromocytoma-induced typical versus atypical Takotsubo cardiomyopathy.

BACKGROUND: A rare presentation of pheochromocytoma (PCC) is catecholamine-induced-cardiomyopathy, or Takotsubo cardiomyopathy (TCM). PCC-induced TCM(PCC-TCM) can present as a typical or atypical type, based on the location of cardiac wall motion abnormalities. In this review, we sought to assess features and outcomes for PCC-TCM, and to compare typical and atypical subtypes. METHODS: A search was conducted on two databases (PubMed and Embase) for case series or reports on PCC-TCM from 2006 to 2020. RESULTS: One-hundred-and-two papers with a total of 104 cases of PCC-TCM were retrieved: 67(64.4%) typical and 37(35.6%) atypical subtypes. Overall median age was 50[range:23-86] years, the atypical group about a decade younger(p < 0.001). A female preponderance was seen for either subtype (∼75%). The most common presentations were chest pain(n = 60;58%), dyspnoea(n = 46;44%), and headache(n = 41;39.4%). Those with atypical subtype more often presented with fluid overload (typical:3% versus atypical:60%); acute pulmonary oedema (35% versus 60%); and cardiogenic shock (22% versus 43%) (all p < 0.05). Six patients (6%) died pre-operatively (typical:8% versus atypical:3%; p = 0.32). Non-fatal pre-operative complications occurred more among those with atypical TCM(p < 0.001), specifically cardiac arrest (typical:5% versus atypical:32%) and respiratory failure (9% versus 24%; both p < 0.05). Overall, 98 underwent surgery, majority undergoing laparoscopic adrenalectomy (81%); similar among the subtypes(p = 0.71). No robust data was provided on short-term outcomes, although two patients suffered from post-operative complications. CONCLUSION: Although quite similar in presentation to either standalone TCM or PCC, PCC-TCM seems to be associated with a higher degree of morbidity and mortality. The atypical PCC-TCM subgroup seems to have a more severe course with possibly a poorer outcome. Further research is needed to make more reliable inferences.

2021 Asia-Pacific Graves' Disease Consortium Survey of Clinical Practice Patterns in the Management of Graves' Disease.

AIM: Although Graves' disease (GD) is common in endocrine practices worldwide, global differences in diagnosis and management remain. We sought to assess the current practices for GD in countries across Asia and the Pacific (APAC), and to compare these with previously published surveys from North America and Europe. METHODS: A web-based survey on GD management was conducted on practicing clinicians. Responses from 542 clinicians were received and subsequently analysed and compared to outcomes from similar surveys from other regions. RESULTS: A total of 542 respondents participated in the survey, 515 (95%) of whom completed all sections. Of these, 86% were medical specialists, 11% surgeons, and 3% nuclear medicine physicians. In addition to serum thyroid-stimulating hormone (TSH) and free thyroxine assays, most respondents would request TSH-receptor autoantibody (TRAb) measurement (68%) during initial work-up. Thyroid ultrasound is requested by about half of respondents (53%), while the use of nuclear medicine scans is limited. The preferred first-line treatment is anti-thyroid drug (ATD) therapy (79%) with methimazole (MMI) or carbimazole (CBZ), followed by radioiodine (RAI; 19%) and surgery (2%). In case of surgery, one-third of respondents would opt for a subtotal rather than a total thyroidectomy. In case of mild Graves orbitopathy (GO), ATDs (67%) remains the preferred treatment, but a larger proportion of clinicians prefer surgery (20%). For a patient with intention to conceive, the preferred treatment pattern remained unchanged, although propylthiouracil (PTU) became the preferred ATD-agent during the first trimester. In comparison to European and American practices, marked differences were noted in the relatively infrequent usage of nuclear medicine scans and the overall higher use of a ATDs and ß-blockers and adjunctive ATD-treatment during RAI in the APAC-group. CONCLUSION: Although regional differences regarding the diagnosis and management of GD are apparent in this first pan-Asia-Pacific survey, this study reveals the overall approach to the management of this disease in Asia-Pacific generally tends to fall between the trends appreciated in the American and European cohorts.

Locally invasive recurrence or metastasis of pheochromocytoma into the liver?-clinicopathological challenges.

Pheochromocytomas (PCC) are rare and functional neuroendocrine tumors developing from adrenal chromaffin cells. Predicting malignant behavior especially in the absence of metastasis can be quite challenging even in the era of improved understanding of the molecular mechanisms involved in PCCs. Currently, two histopathological grading systems Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and Grading of Adrenal Pheochromocytoma and Paraganglioma (GAPP) score are used in clinical practice, but these are subject to significant interobserver variability. Some of the most useful clinical factors associated with malignancy are large size ([4-5 cm), and genetic features such as presence of SDHB germline mutations. Local invasion is uncommon in PCC and metastasis seen in 10 to 17% but higher in germline mutations and when this occurs management can be challenging. Here, we report on a case with challenges faced by the pathologist and clinicians alike in diagnosis and management of PCC recurrence.

Revisiting the Evidence for Routine Transcervical Thymectomy for the Prevention of Thymic Carcinoid Tumours in MEN-1 Patients.

BACKGROUND: Malignant thymic carcinoids are uncommon tumours among patients with multiple endocrine neoplasia type 1 (MEN-1). Current guidelines advise performance of a preventative, routine transcervical thymectomy (TCT) during parathyroidectomy, although data on the yield is scarce. In this review, we aimed to revisit available literature to investigate and summarize the efficacy of routine TCT for the prevention of thymic carcinoid tumours among MEN-1 patients after searching four databases (PubMed, Embase, Medline, and Cochrane Library). SUMMARY: Seven eligible studies were identified: retrospective observational studies: 3 and case reports describing one or more patients: 4. A total of 122 patients were included, 56 males (45.9%) and a pooled mean age of 40 years (±10). All underwent a routine TCT as part of parathyroidectomy; no details on the extent of TCT were available. Overall, only one (0.9%) incidental carcinoid was found. However, although all other patients underwent prophylactic TCT at the time of parathyroidectomy, an additional nine (7.4%) developed a thymic carcinoid during follow-up, after a median time of 36 months (range: 8-226). KEY MESSAGES: There is currently not enough evidence to support the efficacy of a routine TCT to prevent the development of thymic carcinoid among MEN-1 patients. As this is a rare but potentially highly aggressive tumour, attention should be shifted towards improving follow-up programs and developing specific imaging-screening protocols. This enables early detection of thymic carcinoids in a timely manner and improves outcomes, even after performance of a routine TCT.

Continuing challenges of primary neuroendocrine tumours of the thymus: A concisereview.

Primary neuroendocrine tumours of the thymus (NETTs) are exceedingly rare tumours, usually presenting around mid-life, which have a propensity towards males and smokers. They are seen more often in those with MEN-1, but multiple different genetic mutations have been found to be involved in the tumorigenesis of NETTs. Histologically, NETTs are classified according to number of mitoses, the presence of necrosis, and the presence or absence of small cell features. NETTs display a wide spectrum of behavior, and they can be incidentally found on chest imaging, on screening in MEN-1, or present with symptoms of local compression. Advanced disease and paraneoplastic syndromes are common. CT-, PET/CT-, MRI-scans, and somatostatin receptor scintigraphy are the imaging modalities of choice both for the initial assessment as well as for monitoring after treatment. For patients with localized disease, complete surgical resection with lymphadenectomy provides the best chance of long-term, disease-free survival, and can be achieved through either an open or thoracoscopic approach. While chemotherapy-regimens based on platinum, taxane, and temozolomide are used most often, the optimum chemotherapy regimen in the adjuvant and palliative settings remains unclear, as does the role of radiotherapy. Ongoing research on the most effective use of somatostatin analogues, peptide receptor radionuclide therapy (PPRT), kinase inhibitors and immunotherapy in patients with other types of advanced neuroendocrine tumours may lead to further treatment options for NETTs in the future.

Cognitive deficits in primary hyperparathyroidism - what we know and what we do not know: A narrative review.

Classic symptoms of primary hyperparathyroidism (PHPT) are seen in approximately 20% of patients. While features such as kidney stones and skeletal disease are often highlighted as directly related to the disease, others can be even more prevalent. For example, cognitive dysfunction and reduced quality of life are common complaints in many patients, even among those who are classified as being asymptomatic. The pathophysiology of PHPT involves the impact of excess parathyroid hormone (PTH) on calcium metabolism. Referencing putative neurocognitive issues, many animal studies have illustrated the potential roles of PTH and PTH receptors in the brain. Functional imaging and pre-and post-parathyroidectomy studies have suggested a link between the neuronal impact of elevated PTH levels on specific functional aspects of the central nervous system, such as cognition. Confounding a direct role for PTH are hypercalcemia and vitamin D deficiency, both of which could conceivably alter CNS function in PHPT. The lack of strong evidence that parathyroidectomy improves cognition in patients with PHPT raises the question as to whether parathyroid surgery should be recommended on this basis alone. This narrative review summarizes the available literature on neurocognitive function in PHPT.

Hungry bone syndrome following parathyroidectomy for primary hyperparathyroidism in a developed country in the Asia Pacific. A cohort study.

Objectives: We sought to assess the incidence of hungry bone syndrome (HBS) following parathyroidectomy (PTX) for primary hyperparathyroidism (PHPT) in a cohort of multi-ethnic patients from a developed country in the Asia Pacific. Methods: One hundred and sixty-four patients who underwent PTX for PHPT between 2012 and 2019 at the 2 largest public hospitals in Singapore were identified. HBS was defined as serum albumin-adjusted calcium ≤ 2.1 mmol/L with normal or raised serum intact parathyroid hormone (iPTH) levels, manifesting on or after the 3rd day, or persisting for more than 3 days post-operatively. Results: Chinese constituted 73.8%, Malays 12.2%, Indians 9.8%, and other races 4.3%. HBS developed in 4 patients (2.4%) (95% CI, 0.8%-6.5%). HBS patients had significantly longer in-hospital stays; 20 days [IQR:15-22] vs 2 days [IQR:1-3]; P < 0.001in those who did not develop HBS. There was no difference in the incidence of HBS stratifying for age, sex, vitamin D status, or use of preoperative anti-resorptive medication use. For every 10 unit increase in iPTH and alkaline phosphatase (ALP) levels, the risk of HBS increased by 14% and 11%; RR (95% CI), 1.14 (1.05-1.21) and 1.11 (1.03-1.18), respectively. Conclusions: The low incidence of HBS in multi-ethnic patients undergoing PTX by multiple surgeons for PHPT at the 2 largest public hospitals that see the most such patients in Singapore, a developed country, is consistent with the asymptomatic/milder form of presentation of PHPT in the developed world.

The efficacy and safety of cinacalcet in primary hyperparathyroidism: a systematic review and meta-analysis of randomized controlled trials and cohort studies.

Cinacalcet, a positive allosteric modulator of the calcium sensing receptor (CaSR) reduces parathyroid hormone (PTH) secretion by increasing the sensitivity of the CaSR on parathyroid cells. We conducted a systematic review and meta-analysis on the safety and efficacy of cinacalcet in Primary Hyperparathyroidism (PHPT). MEDLINE, Embase, BIOSIS, and the Cochrane Library were searched for published articles (from database inception to Sept 2020). All double-blind RCTs and cohort studies that reported data on the efficacy and safety of cinacalcet therapy in individuals ≥ 18 with PHPT were included. Random effect meta-analysis was performed to estimate the efficacy of cinacalcet in lowering serum calcium and PTH levels compared with placebo. 4 RCTs (177 participants) and 17 cohort studies (763 participants) were eligible for final analysis. Pooled results from the RCTs suggest that, when compared to placebo and administered for up to 28 weeks, cinacalcet normalizes serum calcium (≤ 10.3 mg/dl) in patients with PHPT [RR 20 (95% CI 6.04 - 68.52, I2 = 0%, pheterogeneity < 0·00001)]. Serum PTH levels decreased significantly after 2 weeks and up to 28 weeks after treatment with cinacalcet. In the pooled analysis of the 17 cohort studies, serum calcium levels normalized in 76% (95% CI 66% to 86%; I2 = 92%, pheterogeneity < 0·00001) of patients regardless of the duration of treatment. In most studies, PTH levels decreased by 13% to 55%. No RCT reported on BMD as a primary or secondary outcome, and no improvement in BMD was noted in the 2 non-randomized studies that reported densitometric findings. No significant difference in urinary calcium was noted with cinacalcet therapy in either the RCTs or non-randomized studies. There was no significant difference in overall adverse events (AE) (RD 0.01, 95% CI -0.07 to 0.26) compared to placebo noted in the RCTs. In the non-randomized studies, pooled weighted AE rate was 45% (95% CI 32 to 59%). Risk of bias was low in 2/4 RCTs and 6/17cohort studies; risk was intermediate in 2/4 RCTs and 8/17 cohort studies, and risk was high in 3/17 cohort studies. In PHPT, cinacalcet lowers serum calcium and PTH with greater effects on calcium than on PTH in the short term. In the doses reported, the drug is safe with tolerable side effects. These findings can help inform targeted medical therapy of PHPT in those for whom lowering the serum calcium is indicated and for whom parathyroidectomy is not an option.

Trainee participation does not adversely affect the safety of thyroid surgery: Systematic review and meta-analysis.

Surgical traineeship is essential but must be safe for patients. In thyroid surgery, surgeon volume correlates with improved clinical/economic outcomes. However, it is presently unclear how far does trainee participation affect post-thyroidectomy complication rates in real-world and randomized data. We systematically searched four databases for associations of trainee participation with any post-thyroidectomy outcome. We conducted univariate meta-analyses, sensitivity analyses, and assessed publication bias qualitatively and quantitatively. We included 1 randomized and 15 observational studies from 3755 records, comprising 34 774 thyroid surgical patients. Trainee participation was associated with 12 min longer operative time, but not higher complication rates (hypoparathyroidism, recurrent laryngeal nerve palsy, hematoma, blood loss, return to operating room, hospitalization duration, readmission, and mortality). Sensitivity, publication bias, and multivariate analyses did not change our findings. Real-world and limited randomized data suggest that trainee participation in thyroid surgery is safe, given adequate consultant supervision and appropriate case selection.