Faculty Bibliography

The estimated mortality rates for breast and cervical cancer in Cambodia are high, perhaps because the Cambodian population lacks information about their detection and prevention. This cross-sectional study assessed the distribution of cervical cancers among and the behavioural and clinical characteristics of Cambodian women. It comprised 1039 Cambodian women who were interviewed between August 2013 and January 2016; the interviews were conducted in person using structured questionnaires. Among the participants, 801 (77.2%) and 709 (68.3%) had heard of cervical cancer and cervical cancer detection tests, respectively. However, 830 (80.2%) had never undergone a Pap smear, and 633 (60.9%) had never heard of breast self-examination. Despite the high mortality rates for breast and cervical cancer in Cambodia, only a small percentage of the participants had risk factors (e.g. smoking, alcohol consumption) for female cancers. A nationwide survey of the knowledge, attitudes and practices related to female cancers is recommended.Impact StatementWhat is already known on this subject? The estimated incidence and mortality rates of breast and cervical cancers in Cambodia are high. How much Cambodian women know about these cancers and whether they are receptive to cancer screening are questions requiring further study.What do the results of this study add? To our knowledge, this is the first study to describe the female cancer-related behavioural and clinical characteristics of Cambodian women. We show that rural Cambodian women are mostly unaware of breast and cervical cancer screening and that only a small percentage had risk factors for these cancers, despite the high incidence of these cancers in Cambodia.What are the implications of these findings for clinical practice and/or further research? Our findings potentially aid the design of programmes that increase awareness of breast and cervical cancers in Cambodia. Such programmes would be expected to reduce the incidence and mortality rates of these cancers in this country. Nationwide screening programmes for female cancers should be implemented in Cambodia.

Molecular mechanisms mediating tonic secretion of parathyroid hormone (PTH) in response to hypocalcaemia and hyperparathyroidism (HPT) are unclear. Here we demonstrate increased heterocomplex formation between the calcium-sensing receptor (CaSR) and metabotropic γ-aminobutyric acid (GABA) B₁ receptor (GABA_B1R) in hyperplastic parathyroid glands (PTGs) of patients with primary and secondary HPT. Targeted ablation of GABA_B1R or glutamic acid decarboxylase 1 and 2 in PTGs produces hypocalcaemia and hypoparathyroidism, and prevents PTH hypersecretion in PTGs cultured from mouse models of hereditary HPT and dietary calcium-deficiency. Cobinding of the CaSR/GABA_B1R complex by baclofen and high extracellular calcium blocks the coupling of heterotrimeric G-proteins to homomeric CaSRs in cultured cells and promotes PTH secretion in cultured mouse PTGs. These results combined with the ability of PTG to synthesize GABA support a critical autocrine action of GABA/GABA_B1R in mediating tonic PTH secretion of PTGs and ascribe aberrant activities of CaSR/GABA_B1R heteromer to HPT.

BACKGROUND:The transoral endoscopic approach to thyroidectomy aims to eliminate a visible neck incision. Early experience has demonstrated promising safety and efficacy results but has uncovered unique drawbacks from the middle oral incision. We present a case series of our institutional experience with a technical innovation called the TransOral and Submental Technique (TOaST) designed to address these limitations. MATERIALS AND METHODS:We reviewed all patients who successfully underwent TOaST thyroidectomy at our institution from November 2017 to November 2018. Demographics, surgical indications, technical details, and perioperative outcomes were recorded in a prospective database and analyzed retrospectively. RESULTS:Fourteen patients underwent TOaST thyroidectomy, with mean follow-up of 17 wk. Mean age was 38 y, and all but one was female. Most cases were cytologically benign or indeterminate nodules. There were no injuries to the recurrent laryngeal or mental nerves. TOaST had no instances of chin pain or specimen disruption, two complications that have been associated with the standard transoral approach. The cosmetic outcomes remained excellent. CONCLUSIONS:This pilot study of TOaST indicates that it is a technically feasible and safe approach to thyroidectomy for selected patients.

BACKGROUND:New persistent opioid use has been identified following minor surgical procedures and may contribute to the national opioid epidemic. Prescription patterns vary and we have limited data on patient pain experiences in the outpatient setting. We devised a novel short messaging service survey to record pain scores and opioid use following outpatient thyroid or parathyroid surgery. MATERIALS AND METHODS:Automated short messaging service was sent daily starting the evening of the operation until postoperative day (POD) 10. Pain was assessed on a 0-10 numeric pain rating scale and opioid use over the prior 24 h was queried. RESULTS:A total of 1264 survey questions were sent with overall response rate of 84.3%. Fifty-three of 58 patients had a response rate >50% and were included in the final analysis. Average pain score was highest on POD1 at 3.2. Overall, 42.5% of patients utilized opioids on POD0, 55.6% on POD1, and steadily decreased to 7% by POD10. Overall, 34% of patients did not utilize any opioids postoperatively. Scaled total pain scores were higher in patients with thyroid surgery (23.5 versus 12.1, P = 0.02) and lower in those who reported alcohol use (14.9 versus 31.6, P < 0.02). Scaled total opioid days were lower in those aged >60 (1.5 versus 3.6, P < 0.01) and higher in those with active tobacco use (4.5 versus 2.3, P = 0.04). Pain scores correlated weakly with total opioid days (r = 0.32). CONCLUSIONS:We demonstrate a novel approach of obtaining patient reported daily, prospective pain scores. This may help us understand patient pain and opioid use in the acute postoperative period especially following outpatient surgery.

Importance:Transoral endocrine surgery (TES) allows thyroid and parathyroid operations to be performed without leaving any visible scar on the body. Controversy regarding the value of TES remains, in part owing to the common belief that TES is only applicable to a small, select group of patients. Knowledge of the overall applicability of these procedures is essential to understand the operation, as well as to decide the amount of effort and resources that should be allocated to further study the safety, efficacy, and value of these operations. Objective:To determine what percentage of US patients undergoing thyroid and parathyroid surgery are eligible for TES using currently accepted exclusion criteria. Design, Setting, and Participants:Cross-sectional study of 1000 consecutive thyroid and parathyroid operations (with or without neck dissection) performed between July 1, 2015, and July 1, 2018, at 3 high-volume academic US thyroid- and parathyroid-focused surgical practices (2 general surgery, 1 otolaryngology-head and neck endocrine surgery). Eligibility for TES was determined by retrospectively applying previously published exclusion criteria to the cases. Main Outcomes and Measures:The primary outcome was the percentage of thyroid and parathyroid cases eligible for TES. Secondary outcomes were a subgroup analysis of the percentage of specific types of cases eligible and the reasons for ineligibility. Results:The mean (SD) age of the 1000 surgical patients was 53 (15) years, mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 29 (7), and 747 (75.0%) of the patients were women. Five hundred fifty-eight (55.8%) of the patients were eligible for TES. Most patients with thyroid nodules with cytologically indeterminate behavior (165 of 217 [76.0%]), benign thyroid conditions (166 of 240 [69.2%]), and primary hyperparathyroidism (158 of 273 [57.9%]) were eligible for TES, but only 67 of 231 (29.0%) of patients with thyroid cancer were eligible. Among all 1000 cases reviewed, previous neck operation (97 of 441 [22.0%]), nonlocalized primary hyperparathyroidism (78 of 441 [17.7%]), and need for neck dissection (66 of 441 [15.0%]) were the most common reasons for ineligibility. Conclusions and Relevance:More than half of all patients undergoing thyroid and parathyroid surgery in this study were eligible for TES. This broad applicability suggests that a prospective multicenter trial is reasonable to definitively study the safety, outcomes, and cost of TES.

BACKGROUND:Several malignancies metastasize to the adrenal gland, especially non-small cell lung cancer, renal cell carcinoma, and melanoma. Adrenalectomy is associated with prolonged survival, but laparoscopic adrenalectomy for this indication is controversial. Our objective was to characterize and quantify outcomes after laparoscopic adrenalectomy for metastases to the adrenal gland. METHODS:A prospectively maintained surgical database and institutional cancer registry were queried for patients who underwent adrenalectomy for metastases. From 1995 to 2016, a total of 62 patients underwent adrenalectomy for metastases, with 59 (95.%) having been performed laparoscopically. Primary end points were cumulative probability of 5-year survival and median survival. Patients in the institutional series were compared with Surveillance, Epidemiology, and End Results patients with metastatic non-small cell lung cancer, renal cell carcinoma, and melanoma. RESULTS:There were no deaths within a 30-day period, 6 complications, and 2 conversions to open adrenalectomy. Non-small cell lung cancer (N = 20), renal cell carcinoma (N = 14), and melanoma (N = 8) were the 3 most common adrenal metastases. Overall, cumulative probability of 5-year survival was 37% and median survival was 34 months (95% CI 26-53 months). Median survival for non-small cell lung cancer was 26 months, for renal cell carcinoma was 67 months, and for melanoma was 30 months (P = NS). There was no demonstrable survival benefit for metachronous versus synchronous presentations, no association with size or disease-free interval, nor the presence/history of other metastases. CONCLUSION:Laparoscopic adrenalectomy for metastases is safe when performed by experienced surgeons. Outcomes are similar or improved compared with series with predominantly open adrenalectomies. Patients selected for laparoscopic adrenalectomy to treat metastatic disease also have prolonged survival compared with Surveillance, Epidemiology, and End Results patients with metastatic non-small cell lung cancer, renal cell carcinoma, or melanoma who do not undergo resection of metastatic disease.

BACKGROUND:Aldosterone excess is hypothesized to worsen obstructive sleep apnea (OSA) symptoms by promoting peripharyngeal edema. However, the extent to which primary aldosteronism (PA), hypertension, and body mass index (BMI) influence OSA pathogenesis remains unclear. METHODS:We conducted a cross-sectional study of PA patients from our endocrine database to retrospectively evaluate OSA probability before and after adrenalectomy or medical management of PA. A control group of patients undergoing adrenalectomy for nonfunctioning benign adrenal masses was also evaluated. We categorized patients as high or low OSA probability after evaluation with the Berlin Questionnaire, a validated 10-question survey that explores sleep, fatigue, hypertension, and BMI. RESULTS:We interviewed 91 patients (83 PA patients and eight control patients). Median follow-up time was 2.6 y. The proportion of high OSA probability in all PA patients decreased from 64% to 35% after treatment for PA (mean Berlin score 1.64 versus 1.35, P < 0.001). This decline correlated with improvements in hypertension (P < 0.001) and fatigue symptoms (P = 0.03). Both surgical (n = 48; 1.69 versus 1.33, P < 0.001) and medical (n = 35; 1.57 versus 1.37, P = 0.03) treatment groups demonstrated reduced OSA probability. BMI remained unchanged after PA treatment (29.1 versus 28.6, P = nonsignificant), and the impact of treatment on OSA probability was independent of BMI. The control surgical group showed no change in OSA probability after adrenalectomy (1.25 versus 1.25, P = nonsignificant). CONCLUSIONS:Both surgical and medical treatments of PA reduce sleep apnea probability independent of BMI and are associated with improvements in hypertension and fatigue. Improved screening for PA could reduce OSA burden.

BACKGROUND:The volume of adrenal surgery is increasing. There has been a concern that the widespread use of axial imaging and minimally invasive approaches has led to changing indications for adrenalectomy. We reviewed trends in adrenal surgery at a single academic institution. MATERIALS AND METHODS:This was a retrospective analysis of all patients who underwent adrenal surgery between 1993 and 2018 by the endocrine surgery service. Patient demographics, diagnosis, operative details, and perioperative complications were evaluated. Trend analysis was performed across ordered year groups (<2000, 2000-2004, 2005-2009, 2010-2014, and 2015-2018). RESULTS:We identified 732 patients who underwent 751 adrenal operations. Fifty-seven percent of the patients were women, and the median age was 51 y (range: 5-88). There was an increase in the number of procedures performed (P < 0.01, trend analysis). Over time, there was a higher proportion of patients with hypertension (54.7% [<2000] versus 73.6% [>2015], P < 0.01), diabetes (4.7% versus 22.1%, P = 0.01), and classified as American Society of Anesthesiology class 3/4 (15.7% versus 45.7%, P < 0.01). More patients had their adrenal lesion found incidentally (19.4% versus 39.3%, P < 0.01), and there was a larger proportion of pheochromocytomas (25% versus 36.4%, P < 0.01) and fewer nonfunctioning adenomas (7.4% versus 4.3%, P = 0.03). Median tumor size decreased from 3.5 cm to 2.9 cm (P = 0.03). Complication rates increased over time (8.3% versus 15%, P < 0.01), but the overall 30-d mortality remained low (0.3%). CONCLUSIONS:Adrenal surgery is being performed more commonly with an increasing number of incidentalomas and pheochromocytomas. Our patients have higher comorbidities with increase in complication rates over time, although perioperative mortality remains low. This highlights the importance of a thorough preoperative evaluation to identify suitable patients who may benefit from adrenalectomy.

Medullary thyroid carcinoma (MTC) is a malignant tumor of the parafollicular cells, which produce calcitonin. As a result, calcitonin is an important tool for diagnosing MTC. When there is focal or no calcitonin staining, diagnosis of MTC can be challenging as this may suggest differences in cell origin and in prognosis and recurrence of the disease. The prognosis and guidelines for management and follow up for MTC remain inconclusive. Here, we present a case of primary neuroendocrine tumor of the thyroid gland with only focal calcitonin staining on immunohistochemistry and low serum calcitonin level despite a tumor size of almost 4 cm. The assumption of C-cell origin was made from positive staining for carcinoembryonic agent (CEA), thyroid transcription factor 1 (TTF-1) and paired box 8 (PAX8) without expression of thyroglobulin (Tg). The patient underwent thyroid lobectomy and follow-up monitoring with ultrasound and measurements of calcitonin and CEA levels, without any further surgical intervention. Few cases of neuroendocrine tumors with limited calcitonin expression have been published and the etiology and prognosis are still unknown. Our case suggests that limited calcitonin expression cannot completely exclude the diagnosis of MTC. This rare type of MTC should be differentiated from the typical presentation of MTC. Treatment and post-operative surveillance should be tailored based on the individual.