Undiagnosed Primary Hyperparathyroidism and Recurrent Miscarriage: The First Prospective Pilot Study.

BACKGROUND: Primary hyperparathyroidism (pHPT) in pregnancy is reported to be associated with significant maternal and foetal complications and an up to threefold increase in the risk of miscarriage. However, the true incidence of pHPT in pregnancy, complete and miscarried, is unknown and there are no data on the prevalence of undiagnosed pHPT in recurrent miscarriage (RM) (≥3 consecutive miscarriages under 24-week gestation). This is the first prospective study aiming to establish the prevalence of undiagnosed pHPT in RM. METHODS: Following UK National ethics committee approval, women who had experienced 3 or more consecutive miscarriages were recruited from a nationwide RM clinic. Serum corrected calcium, phosphate, PTH and vitamin D were evaluated. Patients with raised serum calcium and/or PTH were recalled for confirmatory tests. Power calculations suggested that a minimum of 272 patients were required to demonstrate a clinically significant incidence of pHPT. RESULTS: Three hundred women were recruited, median age 35 years (range 19-42). Eleven patients had incomplete data, leaving 289 patients suitable for analysis; 50/289 patients (17%) with abnormal tests were recalled. The prevalence of vitamin D deficiency (<25 nmol/l) and insufficiency (25-75 nmol/l) was 8.7 and 67.8%, respectively. One patient was diagnosed with pHPT (0.34%) and underwent successful parathyroidectomy. CONCLUSIONS: The prevalence of undiagnosed pHPT (0.34%) in RM in this study appears to be many times greater than the 0.05% expected in this age group. The findings of this pilot study merit follow-up with a larger-scale study. Routine serum calcium estimation is not currently undertaken in RM and should be considered.

Is estrogen exposure a protective factor for pancreatic neuroendocrine tumours in female patients with multiple endocrine neoplasia syndrome type 1?

OBJECTIVE: Pancreatic neuroendocrine tumours (PNETs) are the most common cause of death in patients with multiple endocrine neoplasia type 1 (MEN1). Women have been shown to have improved survival, which may suggest a possible protective effect of female sex hormones. The aim of this study was to evaluate the relationship between estrogen exposure and PNET tumourigenesis, tumour growth and survival in female MEN1 patients with these tumours. DESIGN: We performed a retrospective chart review of the existing MEN1 database in our institution. Detailed information about female patients' menstrual and reproductive history, and PNET clinicopathologic characteristics was collected. Questionnaires regarding estrogen exposure were used to collect information that was missing in the database. PATIENTS: Of 293 confirmed MEN1 cases, 141 women met the inclusion criteria. MEASUREMENTS: We used measures of cumulative estrogen exposure time (CEET), parity, live birth pregnancies and bilateral oophorectomy to estimate estrogen exposure. RESULTS: There was no significant association between CEET and time to PNET diagnosis (hazard ratio = 0·966, P = 0·380). For the correlation between estrogen exposure and PNET type, size, numbers, distant metastasis, lymph node metastasis, lymphovascular invasion, AJCC (American Joint Committee on Cancer) stage and overall survival, only CEET was significantly correlated with PNET size (P = 0·043). CONCLUSIONS: In female patients with MEN1, estrogen exposure may inhibit PNET growth. A demonstrable protective effect against PNET tumourigenesis, tumour growth and survival of patients with these tumours may require a larger cohort.

Clinical features and prognosis of thymic neuroendocrine tumours associated with multiple endocrine neoplasia type 1: A single-centre study, systematic review and meta-analysis.

OBJECTIVE: Thymic neuroendocrine tumour (TH-NET) accounts for almost 20% of multiple endocrine neoplasia type 1 (MEN1)-associated mortality. Identifying risk factors for the development of these rare tumours and prognostic factors for clinical outcomes will be helpful in clinical practice. DESIGN AND PATIENTS: We performed a retrospective analysis of patients treated for TH-NET associated with MEN1 in a single institution and meta-analysis of literature reports. We used a fixed effect model to pool results across studies to evaluate the prevalence, clinical features and prognosis. RESULTS: TH-NET was detected in 9 (7.4%) of 121 patients with MEN1 seen in our institution, and 5 (55.6%) were women. Seven additional studies were identified through a systematic review of the literature. The pool estimate of TH-NET prevalence was 3.7% (n = 99) in MEN1 (n = 2710), sex ratio was 79:20 (male vs female), and the median age at diagnosis was 43.0 years (range, 16.0-72.0 years). Forty-three patients died with a median survival time of 8.4 years. Older age at diagnosis (HR = 1.4, 95% CI = 1.0-1.8, P = .03), maximum tumour diameter (HR = 1.5, 95% CI = 1.0-2.3, P = .04) and presence of metastasis (HR = 1.6, 95% CI = 1.0-2.5, P = .04) were associated with worse outcome. A male predominance (91.9% vs 59.5%, P < .001) and history of smoking (59.0% vs 23.5%, P = .015) were more common in American/European series compared to Asian reports. CONCLUSION: TH-NET is a rare but fatal component of MEN1. Earlier detection of TH-NET in patients with MEN1 may be recommended which should theoretically result in better outcomes. Different genetic backgrounds (race) appear to result in clinical difference.

Differentiating Atypical Parathyroid Neoplasm from Parathyroid Cancer.

INTRODUCTION: The differentiation of benign parathyroid gland atypia and true parathyroid carcinoma (PC) can be challenging. In some instances, patients are classified as having 'atypical parathyroid neoplasms' (APNs), explicitly acknowledging that the distinction between benign and malignant disease appears impossible to determine. This 'grey area' diagnosis makes rendering an accurate prognosis difficult, and clouds clinical management and treatment planning. METHODS: We performed a retrospective chart review of all patients undergoing operation for primary hyperparathyroidism in our institution (2000-2014). Patients with a histopathological diagnosis of PC or APN were included. Demographics, clinical characteristics, and survival rates were analyzed, and analysis was conducted using SAS 9.4 (SAS Institute, Inc., Cary, NC, USA). RESULTS: Fifty-four patients were included in the study-31 (57.41 %) with PC and 23 (42.59 %) with APN. PC versus APN was associated with higher parathyroid hormone (PTH) (p = 0.005) and with males (p = 0.002). Five-year overall survival (OS) from diagnosis was 82.64 % [95 % confidence interval (CI) 59.82-93.17] for the PC group and 93.33 % (95 % CI 61.26-99.03) for the APN group, while the 5-year recurrence-free survival rate was 59.63 % (95 % CI 36.32-76.81) in the PC group and 90.91 % (95 % CI 50.81-98.67) in the APN group. CONCLUSION: PC and APN are distinct clinical entities with differences in tumor biology reflected in overall recurrence rates, disease-free survival, and OS. APNs present with a less accentuated biochemical profile and demonstrate an indolent clinical course compared with PCs. Efforts to improve categorization and staging of PC and APN are needed.

Utility of chromogranin A, pancreatic polypeptide, glucagon and gastrin in the diagnosis and follow-up of pancreatic neuroendocrine tumours in multiple endocrine neoplasia type 1 patients.

OBJECTIVE: Pancreatic neuroendocrine tumours (PNETs) are the major source of disease-specific mortality in multiple endocrine neoplasia type 1 (MEN1) patients. Chromogranin A (CgA), pancreatic polypeptide (PP), glucagon and gastrin have some diagnostic value in sporadic PNETs, but there is very little evidence for their efficacy in diagnosing PNETs in MEN1 patients. DESIGN: We performed a retrospective chart review of the existing MEN1 database in our institution. PATIENTS: One hundred and thirteen patients were eligible for diagnostic value analysis of tumour markers. Patients were excluded if measurement of tumour markers was missing, either 3 months prior to PNET diagnosis (PNET patients) or prior to abdominal imaging (non-PNET patients). MEASUREMENTS: Clinicopathologic characteristics and of tumour marker measurements were analysed. RESULTS: Of 293 confirmed MEN1 cases, 55 PNETs and 58 non-PNETs met inclusion criteria. The area under the curve (AUC) for CgA, PP, glucagon and gastrin in MEN1 cases was 59·5%, 64·1%, 77·0% and 75·9%, respectively. The AUC for the combination of CgA, PP and gastrin was 59·6%. PP, but not CgA, glucagon or gastrin was significantly associated with both age and PNET functional status (P = 0·0485 and 0·0188, respectively). No markers were significantly associated with sex, PNET size, tumour number, tumour location, American Joint Committee on Cancer (AJCC) stage, presence of lymph node metastasis, lymphovascular invasion or overall survival. CgA values were not significantly lower following PNET resection than pre-operatively (P = 0·554). CONCLUSIONS: The value of blood markers for diagnosing PNETs in MEN1 patients is relatively low, even when used in combination.

Oncologic progress for the treatment of parathyroid carcinoma is needed.

BACKGROUND AND OBJECTIVES: Parathyroid carcinoma (PC) is rare but potentially lethal. No standardized staging system or treatment guidelines have been established. We aimed to determine whether management of PC and patient outcomes have changed at our institution over the past 35 years. METHODS: Retrospective review of patients with PC at our institution between 1980 and 2015. Patients were grouped by date of initial surgery: group 1, 1980-2001; group 2, 2002-2015. RESULTS: About 57 patients (26 in group 1; 31 in group 2) were included. Group 2 had more female patients (61%) than group 1 (31%; P = 0.033). Patients in group 2 were older at the time of initial operation (mean age 48 years in group 1 (SD:14.3) and 56 years (SD:14.6) in group 2; P = 0.034). The 5-year OS rates were 82% (95%CI 59.6%, 93%) for group 1 and 72% (95%CI 45.0%, 87.7%) for group 2. The 5-year DFS rates were 62% (95%CI 36.4%, 79.9%) for group 1 and 66% (95%CI 40.6%, 82.2%) for group 2. CONCLUSION: Management of PC and patient outcomes (OS and DFS) have not significantly changed over the past 35 years at our institution. This rare malignancy needs oncologic improvement. J. Surg. Oncol. 2016;114:708-713. © 2016 Wiley Periodicals, Inc.

Learning curve of vessel cannulation in rats using cumulative sum analysis.

BACKGROUND: Intravascular access routes are widely used for administering agents or taking blood samples in rodents. Vessel cannulation in rats is a technically challenging procedure with a risk for significant complications. The use of cumulative sum (CUSUM) analysis allows continuous monitoring of the performer's outcomes to evaluate the learning curve for a particular procedure. The aim of the present study was to assess a researcher's learning curve in the cannulation of the jugular and femoral vein in rats using CUSUM analysis. MATERIALS AND METHODS: A single researcher performed two hundred microsurgical operations between September 2012 and September 2013. The animals (male Wistar rats) were anesthetized with isoflurane whereas the right jugular vein and the left femoral vein were catheterized. Prospective data were collected and analyzed using CUSUM analysis. For the purposes of the study, the rat population was divided in four groups based on the order of studies; group 1 represents the first 50 animals cannulated, group 2 the next batch of 50 animals, and so forth. RESULTS: The operating times required for cannulation of the jugular vein for groups 1, 2, 3, and 4 were 24.6 ± 4.8, 15.9 ± 2.5, 15.2 ± 3.2, and 15.7 ± 3.3 min, respectively. Group 1's operating time was significantly longer than all the other groups (P < 0.001 compared with all other groups). The operating times for groups 2, 3, and 4 did not differ significantly (P > 0.05). The cannulation of the femoral vein required a mean of 32 ± 5.3 min for group 1, 24.9 ± 5.7 min for group 2, 18.4 ± 4 min for group 3, and 17.2 ± 3.4 min for group 4. The operating time of group 1 was significantly longer when compared with all groups (P < 0.001 for all groups). Group 2 also had a longer operating time than groups 3 and 4 (P < 0.001 compared with both groups). Groups 3 and 4 did not show any statistical significant difference when their operating time was compared (P > 0.05). CUSUM analysis suggested that the number of cases required to achieve the required experience to most effectively cannulate the jugular and femoral vein is approximately 50 and 100 cases, respectively. The adverse effects of the procedure included two unexpected deaths, both of which occurred in group 1 (0.5% in total). CONCLUSIONS: The authors' experience regarding the learning curve of the cannulation of the femoral and jugular vein in rats from 200 animals operated over a period of 1 y for the evaluation of the pharmacokinetic properties of drug candidates suggests significant experience is required to optimize the operating time required for the procedure.

Retroperitoneoscopic or laparoscopic adrenalectomy? A single-centre UK experience.

BACKGROUND: Laparoscopic adrenalectomy (LA) is the "gold standard" approach to benign adrenal tumours. Retroperitoneoscopic adrenalectomy (RA) is an increasingly popular alternative. The purpose of this study was to compare our preliminary experience with RA to the more established LA. METHODS: Data on patients undergoing adrenalectomy over a 2-year period from 2010 were reviewed. Patients undergoing open adrenalectomy, bilateral adrenal surgery, or paraganglioma resection were excluded. The LA and RA patients were compared according to their operative time, time to first oral intake, complications, analgesic requirements, and length of hospital stay. Further analysis was performed on patients matched for all patient and disease-related criteria. Statistical analysis was performed using the χ (2) test and the Mann-Whitney U test as appropriate. RESULTS: A total of 71 adrenalectomies that fit the inclusion criteria were performed during the period studied of which 36 patients underwent LA and 35 patients underwent RA. Mean tumour size differed between the two groups (2.83 cm in RA group vs. 4.1 cm in LA group; p = 0.033). Operative time, time to first oral intake, analgesic requirements, length of hospital stay, and postoperative complications were all significantly lower in the RA group. Analysis of matched patients showed a significant difference between RA and LA in analgesia requirements (5 vs. 8 paracetamol doses, p = 0.014; 2 vs. 10 tramadol doses, p = 0.042) as well as in the length of hospital stay (1.58 vs. 3.58 days, p = 0.038). CONCLUSIONS: RA may be associated with reduced postoperative pain and length of hospital stay. It is a valuable alternative to LA in smaller tumours where it may prove to be superior.

Analysis of false-positive and false-negative results in 99mTc-MIBI SPECT/CT parathyroid imaging.

Background: Exact preoperative localization is desirable to perform minimally invasive parathyroidectomy for hyperparathyroidism (HPT). This study aimed to evaluate the diagnostic values of 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) single photon emission computed tomography/computed tomography (SPECT/CT) of parathyroid glands by analyzing the relationship between lesion weight and false-negative (FN) results, as well as to explain the possible reason. Methods: The data from 314 patients with suspected HPT who underwent 99mTc-MIBI SPECT/CT parathyroid imaging between 2011 and 2022 were retrospectively evaluated. The sensitivity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of parathyroid 99mTc-MIBI SPECT/CT were calculated, and the false-positive (FP) and FN findings were analyzed. Results: Accurate localization by 99mTc-MIBI SPECT/CT was significantly associated with the parathyroid hormone (PTH) level. The 99mTc-MIBI SPECT/CT for diagnosis/lesion location reached a sensitivity of 84.6%/56.8%, a PPV of 97.3%/98.4%, an NPV of only 23.7%/4.18%, and an accuracy of 83.4%/57.1%, respectively. The largest diameter, shortest diameter, and lesion volume were lower in the FN group than in the TP group. A total of 7 FP cases were found, including 2 cases of thyroid nodules, 4 cases of thyroid tissue, and 1 case of hibernoma. A total of 45 FN patients, including 321 FN lesions, were confirmed, of which parathyroid hyperplasia accounted for 97.8%. Lesion weights greater than 20 µg were able to be detected, but lightweight lesions less than 100 mg were the principal source of FN results, accounting for approximately 39.3%. With lesion weights 0-100, 101-300, 301-1,000, and >1,000 mg, the FN rate was 70.8% (126/178), 51.8% (103/199), 34.6% (81/234), and 8.33% (11/132), respectively. Conclusions: 99mTc-MIBI SPECT/CT parathyroid imaging provides good sensitivity and high specificity in HPT location. Correct localization by 99mTc-MIBI SPECT/CT correlates positively with lesion weight and PTH levels. The smaller the lesion, the higher the FN rate in 99mTc-MIBI SPECT/CT parathyroid imaging, and lesions weighing less than 100 mg are the main source of FN results in 99mTc-MIBI SPECT/CT parathyroid imaging.

Vertical sleeve gastrectomy normalizes circulating glucocorticoid levels and lowers glucocorticoid action tissue-selectively in mice.

Objectives: Glucocorticoids produced by the adrenal cortex are essential for the maintenance of metabolic homeostasis. Glucocorticoid activation is catalysed by 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1). Excess glucocorticoids are associated with insulin resistance and hyperglycaemia. A small number of studies have demonstrated effects on glucocorticoid metabolism of bariatric surgery, a group of gastrointestinal procedures known to improve insulin sensitivity and secretion, which were assumed to result from weight loss. In this study, we hypothesize that a reduction in glucocorticoid action following bariatric surgery contributes to the widely observed euglycemic effects of the treatment. Methods: Glucose and insulin tolerance tests were performed at ten weeks post operatively and circulating corticosterone was measured. Liver and adipose tissues were harvested from fed mice and 11ß-HSD1 levels were measured by quantitative RT-PCR or Western (immuno-) blotting, respectively. 11ß-HSD1 null mice (Hsd11b1 -/-) were generated using CRISPR/Cas9 genome editing. Wild type and littermate Hsd11b1 -/- mice underwent Vertical Sleeve Gastrectomy (VSG) or sham surgery. Results: Under the conditions used, no differences in weight loss were observed between VSG treated and sham operated mice. However, both lean and obese WT VSG mice displayed significantly improved glucose clearance and insulin sensitivity. Remarkably, VSG restored physiological corticosterone production in HFD mice and reduced 11ß-HSD1 expression in liver and adipose tissue post-surgery. Elimination of the 11ß-HSD1/Hsd11b1 gene by CRISPR/Cas9 mimicked the effects of VSG on body weight and tolerance to 1g/kg glucose challenge. However, at higher glucose loads, the euglycemic effect of VSG was superior to Hsd11b1 elimination. Conclusions: Bariatric surgery improves insulin sensitivity and reduces glucocorticoid activation at the tissular level, under physiological and pathophysiological (obesity) conditions, irrespective of weight loss. These findings point towards a physiologically relevant gut-glucocorticoid axis, and suggest that lowered glucocorticoid exposure may represent an additional contribution to the health benefits of bariatric surgery.

Gastric perforation secondary to Rapunzel syndrome.

Rapunzel syndrome is rare and describes a trichobezoar that extends through the pylorus into the jejunum, ileum or even the colon. Due to the large intraluminal size and weight they can attain, acute presentations of obstruction or perforation may occur. We report a case of a 17-year-old girl who presented to the emergency department following a syncopal episode. On examination, a left upper quadrant mass was appreciated with no signs of peritonism. Contrast-enhanced CT demonstrated a giant trichobezoar with resulting gastric perforation and intra-abdominal free fluid. Laparotomy and gastrotomy were performed and the patient had an uneventful recovery with psychiatric review prior to discharge. Though uncommon, bezoars should be included in our differential diagnosis as they can present in various ways owing to their size and weight. This case illustrates the risk of gastric perforation with large gastric bezoars.

Understanding the clinical course of genotype-negative MEN1 patients can inform management strategies.

BACKGROUND: It is unclear whether genotype-negative clinical multiple endocrine neoplasia type 1 patients derive equal benefit from prospective surveillance as genotype-positive patients. METHODS: In this retrospective cohort study, we compared genotype-negative patients with clinical multiple endocrine neoplasia type 1 with genotype-positive index cases. Primary outcome was age-related penetrance of manifestations; secondary outcomes were disease-specific survival and clinical course of endocrine tumors. RESULTS: We included 39 genotype-negative patients with clinical multiple endocrine neoplasia type 1 (Male: 33%) and 63 genotype-positive multiple endocrine neoplasia type 1 index cases (Male: 59%). Genotype-negative patients with clinical multiple endocrine neoplasia type 1 were 65 years old at last follow-up; genotype-positive multiple endocrine neoplasia type 1 index cases were 50 (P < .001). Genotype-negative patients with clinical multiple endocrine neoplasia type 1 were significantly older at their first and second primary manifestation. Only 1 developed a third primary manifestation. No genotype-negative patients with clinical multiple endocrine neoplasia type 1 with primary hyperparathyroidism and a pituitary adenoma developed a duodenopancreatic neuroendocrine tumor. Disease-specific survival was significantly better in genotype-negative patients with clinical multiple endocrine neoplasia type 1. In genotype-negative patients with clinical multiple endocrine neoplasia type 1, primary hyperparathyroidism was single-gland disease in 47% of parathyroidectomies versus 0% in genotype-positive multiple endocrine neoplasia type 1 index cases. In genotype-negative patients with clinical multiple endocrine neoplasia type 1, 17% of duodenopancreatic neuroendocrine tumors were multifocal versus 68% in genotype-positive multiple endocrine neoplasia type 1 index cases. Genotype-negative patients with clinical multiple endocrine neoplasia type 1 had more pituitary macroadenomas, fewer prolactinomas, and more somatotroph adenomas. CONCLUSION: Genotype-negative patients with clinical multiple endocrine neoplasia type 1 have a different clinical course than genotype-positive multiple endocrine neoplasia type 1 index cases. This may support a separate classification and a tailored surveillance regimen. Of the genotype-negative patients with clinical multiple endocrine neoplasia type 1 who had parathyroidectomy, almost half had no evidence of multigland disease and may be potential candidates for a more targeted single-gland approach.

Children are at a high risk of hypocalcaemia and hypoparathyroidism after total thyroidectomy.

PURPOSE: Disruption of calcium homeostasis is the most common complication after total thyroidectomy in adults. We explored the incidence and risk factors of hypocalcaemia and hypoparathyroidism after total thyroidectomy in children (≤18 years of age). METHODS: One hundred six children underwent total thyroidectomy. Patient, operative and outcome data were collected and analyzed. RESULTS: The indication for surgery was Graves' disease in 52 children (49.1%), Multiple Endocrine Neoplasia type-2 in 36 (33.9%), multinodular goiter in 3 (2.8%) and follicular/papillary thyroid carcinoma in 15 (14.2%). Neck dissection was performed in 23 children (18.9%). In 14 children (13.2%), autotransplantation was performed; in 31 (29.2%), ≥1 glands were found in the specimen. Hypocalcaemia within 24 h of thyroidectomy was observed in 63 children (59.4%) and 52 (49.3%) were discharged on supplements. Hypoparathyroidism at 6 months persisted in 23 children (21.7%). The ratios of all forms of calcium-related-morbidity were larger among children with less than four parathyroid glands remaining in situ: hypocalcaemia within 24 h of thyroidectomy (54.0% versus 47.5%; p = 0.01), hypoparathyroidism on discharge (64.4% versus 37.7%; p = 0.004) and long-term hypoparathyroidism (31.1% versus 14.8%; p = 0.04). CONCLUSION: The incidence of postoperative hypocalcaemia and hypoparathyroidism among children undergoing total thyroidectomy is considerable. The inability to preserve the parathyroid glands in situ during surgery seems an important factor. For optimal outcomes, the parathyroid glands should be preserved in situ. TYPE OF STUDY: Prognosis Study. LEVEL OF EVIDENCE: Level IV.

Long-term quality of voice is usually acceptable after initial hoarseness caused by a thyroidectomy or a parathyroidectomy.

BACKGROUND: Vocal cord (VC) palsy following a thyroidectomy or parathyroidectomy can result in significant morbidity for the patient. We aimed to investigate the incidence of VC palsy in a tertiary referral Institution, track the management of these cases and record the long-term outcomes and VC recovery rates. METHODS: Retrospective review of all thyroidectomy/parathyroidectomy operations performed over 11 years. Patients with an unequivocal hoarse voice postoperatively were included. We analysed the patient's clinical characteristics and voice outcomes, operative, pathology and laryngoscopy reports during their follow-up. RESULTS: Ten patients fitted the inclusion criteria and were analysed. Median age at date of operation was 47.5 years (range, 16-81 years) and the M:F ratio was 1:2.3 (M:3, F:7). The median FU was 62.5 months (range, 12-144 months). The median hospital stay was 1.5 days (range, 1-87 days). There were 7 recurrent laryngeal nerve (RLN) injuries by manipulation, 1 case of RLN resection, 1 inadvertent division (with primary nerve repair) and 1 RLN was shaved off the thyroid. Long-term voice outcomes for the 7 patients with an RLN manipulation injury were: 3/7 patients had normal voice, 3/7 had moderate hoarseness and 1/7 had long-term hoarseness. The long-term voice outcome of the patient with RLN shaving off the thyroid gland was excellent while the 2 remaining patients (RLN resection and inadvertent division) needed 12 and 18 months respectively to achieve a normal quality of voice. Four out of the 10 patients had permanent VC palsy in the long-term and their voice outcomes varied: 1 patient had a normal voice, 2 patients had moderate hoarseness and 1 patient had persistent hoarseness. Only 1/10 patients did not show any voice improvement after 12 months. CONCLUSIONS: In the vast majority of cases post-operative hoarseness due to RLN palsy improves in the long-term, albeit voice may not return completely to normal.

Establishing a successful rat model of duodenal- jejunal bypass: A detailed guide.

Gastric bypass surgery, an operation that restricts the stomach and bypasses the duodenum and part of the jejunum, results in major improvement or remission of type 2 diabetes. Duodenual-jejunal bypass was developed by one of the authors (FR) as an experimental, stomach-sparing variant of gastric bypass surgery to investigate weight-independent mechanisms of surgical control of diabetes. Duodenual-jejunal bypass has been shown to improve various aspects of glucose homeostasis in rodents and in humans, thus providing an experimental model for investigating mechanisms of action of surgery and elusive aspects of gastrointestinal physiology. Performing duodenual-jejunal bypass in rodents, however, is associated with a steep learning curve. Here we report our experience with duodenual-jejunal bypass and provide practical tips for successful surgery in rats. Duodenual-jejunal bypass was performed on 50 lean rats as part of a study aimed at investigating the effect of the procedure on the physiologic mechanisms of glucose homeostasis. During the study, we have progressively refined details of anatomic exposure, technical aspects of duodeno-jejunostomy and peri-operative care. We analysed the role of such refinements in improving operative time and post-operative mortality. We found that refinement of exposure methods of the gastro-duodenal junction aimed at minimizing tension on small visceral vasculature, technical aspects of duodeno-jejunal anastomosis and peri-operative management played a major role in improving the survival rate and operative time. Overall, an experimental model of duodenual-jejunal bypass was successfully reproduced. Based on this experience, we describe here what we believe are the most important technical tips to reduce the learning curve for the procedure.

Seventeen Cases of Primary Hyperparathyroidism in Pregnancy: A Call for Management Guidelines.

CONTEXT: The risks of primary hyperparathyroidism (pHPT) to pregnant women and their fetuses appear to increase commensurate with serum calcium levels. The management strategy for pHPT must be adapted in pregnancy and should reflect the severity of hypercalcemia. However, no guidelines exist to assist clinicians. METHODS: The experience of a high-volume multidisciplinary endocrine surgical service in treating a consecutive series of pregnant women with pHPT referred for parathyroidectomy is presented and data are compared with a nonpregnant cohort with pHPT. A review of pHPT and pregnancy outcomes in the literature is provided. RESULTS: Seventeen pregnant women and 247 age range-matched nonpregnant women with pHPT were referred for surgery over 11 years. Mean serum calcium level was higher in the pregnant cohort (2.89 vs 2.78 mmol/L; P = 0.03). Preoperative localization with ultrasound succeeded in eight pregnant women (47%) and sestamibi scanning did in two of six (33% imaged preconception), compared with 84 (34%) and 102 (42%) control subjects, respectively (not significant). Parathyroidectomy was performed under general anesthesia between 12 and 28 weeks' gestation with no adverse pregnancy outcomes resulting. Cure rate was 100% vs 96% in controls. CONCLUSION: pHPT in pregnancy is a threat to mother and child. Medical management may be appropriate in mild disease, but in moderate to severe disease, parathyroidectomy under general anesthesia in the second trimester is safe. Localization using ionizing radiation/MRI is unnecessary, because surgical intervention in a high-volume multidisciplinary setting has excellent outcomes. Guidelines on the topic would assist clinicians.

Using a Novel Diagnostic Nomogram to Differentiate Malignant from Benign Parathyroid Neoplasms.

We sought to develop an immunohistochemical (IHC) tool to support the diagnosis of parathyroid carcinoma (PC) and help differentiate it from atypical parathyroid neoplasms (atypical) and benign adenomas. Distinguishing PC from benign parathyroid neoplasms can be challenging. Many cases of PC are histopathologically borderline for definitive malignancy. Recently, individual IHC biomarkers have been evaluated to aid in discrimination between parathyroid neoplasms. PC, atypical parathyroid neoplasms, and parathyroid adenomas treated at our institution from 1997 to 2014 were studied retrospectively. IHC analysis was performed to evaluate parafibromin, retinoblastoma (RB), protein gene product 9.5 (PGP9.5), Ki67, galectin-3, and E-cadherin expression. Receiver operating characteristic (ROC) analysis and multivariable logistic regression model for combinations of biomarkers were evaluated to classify patients as PC or atypical/adenoma. A diagnostic nomogram using 5 biomarkers was created for PC. Sixty-three patients were evaluated. The percent staining of parafibromin (p < 0.0001), RB (p = 0.04), Ki67 (p = 0.02), PGP9.5 (p = 0.04), and Galectin-3 (p = 0.01) differed significantly in the three diagnostic groups. ROC analysis demonstrated that parafibromin had the best performance in discriminating PC from atypical/adenoma; area under the curve (AUC) was 81% (cutoff, 92.5%; sensitivity rate, 64%; specificity rate, 87%). We created a diagnostic nomogram using a combination of biomarkers; AUC was 84.9% (95% confidence interval, 73.4-96.4%). The optimism-adjusted AUC for this model was 80.5% (mean absolute error, 0.043). A diagnostic nomogram utilizing an immunoexpression, a combination of immunohistochemical biomarkers, can be used to help differentiate PC from other parathyroid neoplasms, thus potentially improving diagnostic classification.

Operation duration and adrenal gland size, but not BMI, are correlated with complication rate for posterior retroperitoneoscopic adrenalectomy for benign diseases.

BACKGROUND: We sought to determine whether obesity is correlated with complications after posterior retroperitoneoscopic adrenalectomy for benign diseases and to develop surrogate markers of abdominal fat in preoperative computed tomography. METHODS: We conducted a retrospective chart review of all patients who had undergone posterior retroperitoneoscopic adrenalectomy and preoperative computed tomography between January 1, 2008 and December 31, 2015. The cross-sectional components of fat assessed by computed tomography included total fat area, subcutaneous fat area, retroperitoneal fat area, and peritoneal fat area. The patients were grouped into 2 categories according to the absence or presence of a postoperative complication (the no-complications group and the complications group, respectively). RESULTS: Of 116 study patients, 20 patients (17%) had a postoperative complication. Operations of greater duration and smaller adrenal gland size were significantly correlated with complications both in univariate and multivariate analyses. Body mass index, total fat area, subcutaneous fat area, retroperitoneal fat area, peritoneal fat area, and distance of skin to muscle (in axial and sagittal images) correlated with complications in univariate analysis but not in multivariate analysis. In the no-complications group, the removed adrenal gland was larger than that removed in the complications group (6 vs 4 cm, respectively, P = .001), whereas the complications group had a greater operative duration (139 vs 104 min, respectively, P = .001) and a greater duration of hospital stay (3 days vs 1 day, respectively, P = .001). CONCLUSION: In this study, operations of greater duration and smaller adrenal gland size were better predictors of complications after posterior retroperitoneoscopic adrenalectomy for benign disease than measures of obesity, including body mass index.

Comprehensive Genomic Characterization of Parathyroid Cancer Identifies Novel Candidate Driver Mutations and Core Pathways.

CONTEXT: Elucidating the genomic landscape of sporadic parathyroid carcinoma (PC) has been limited by low tumor incidence. OBJECTIVE: Identify driver mutations of sporadic PC and potential actionable pathways. METHODS: Patients undergoing surgical resection for sporadic PC between 1980 and 2016 at MD Anderson Cancer Center were identified. Patients with sporadic PC according to World Health Organization diagnostic criteria and with available formalin-fixed, paraffin-embedded (FFPE) PC tumor tissue were included and their clinical data analyzed to assess extent of disease. Patients with parathyroid tumors of uncertain malignancy or atypical parathyroid neoplasms were excluded. Thirty-one patients meeting diagnostic criteria had available tissue for analysis. FFPE PC tumors were subjected to DNA extraction and next-generation whole-exome sequencing. All variant calls are single-algorithm only. Twenty-nine samples passed quality assurance after DNA extraction. MAIN OUTCOME MEASURES: Somatic or private germline mutations present in sporadic PC and identification of pathways involved in tumorigenesis. RESULTS: We identified 35 genes with considerable mutational load; only eight genes were previously identified in other PC cohorts. These genes mediate critical processes, including chromosome organization, DNA repair, and cell cycle regulations. Gene mutations involved in MAPK signaling and immune response are also heavily implicated. These findings are limited by inherent molecular artifacts in FFPE tissue analysis and the absence of matched germline DNA. Additionally, variant calls are only single algorithm and may include false-positive/negative calls. CONCLUSION: We identified 33 candidate driver genes of sporadic PC, in addition to previously known driver genes CDC73 and MEN1.

Metastasis to the thyroid gland from a tonsil squamous cell carcinoma.

We present a case of rare metastasis of tonsil squamous cell carcinoma to the thyroid gland, after 2 years of treatment without recurrence at the primary site. The patient had incidental finding of a nodule in the left lobe of the thyroid gland during a screening scan for his previous tonsil squamous cell carcinoma that was treated surgically 2 years ago. The patient was completely asymptomatic with normal thyroid function tests. After further investigations and discussion in the MDT meeting, the patient underwent left thyroid lobectomy as a definitive treatment for his thyroid metastasis.