Incidental parathyroidectomy in thyroidectomy and central neck dissection

BackgroundAlthough higher thyroidectomy volume has been linked with lower complication rates, its association with incidental parathyroidectomy remains less studied. The volume relationship is even less clear for central neck dissection, where individual parathyroid glands are at greater risk.MethodsPatients undergoing thyroidectomy with or without central neck dissection were evaluated for incidental parathyroidectomy, hypoparathyroidism, and hypocalcemia. Univariate and multivariable analyses were performed using binary logistic regression.ResultsOverall, 1,114 thyroidectomies and 396 concurrent central neck dissections were performed across 7 surgeons. Incidental parathyroidectomy occurred in 22.4% of surgeries (range, 16.9%–43.6%), affecting 7.1% of parathyroids at risk (range, 5.8%–14.5%). When stratified by surgeon, lower incidental parathyroidectomy rates were associated with higher thyroidectomy volumes (R² = 0.77, P = .008) and higher central neck dissection volumes (R² = 0.93, P < .001). On multivariable analysis, low-volume surgeon (odds ratio 2.94, 95% confidence interval 2.06–4.19, P < .001), extrathyroidal extension (odds ratio 3.13, 95% confidence interval 1.24–7.87, P = .016), prophylactic central neck dissection (odds ratio 2.68, 95% confidence interval 1.65–4.35, P <.001), and therapeutic central neck dissection (odds ratio 4.44, 95% confidence interval 1.98–9.96, P < .001) were the most significant factors associated with incidental parathyroidectomy. In addition, incidental parathyroidectomy was associated with a higher likelihood of temporary hypoparathyroidism (odds ratio 2.79, 95% confidence interval 1.45–5.38, P = .002) and permanent hypoparathyroidism (odds ratio 4.62, 95% confidence interval 1.41–5.96, P = .025), but not permanent hypocalcemia (odds ratio 1.27, 95% confidence interval 0.48–3.35, P = .63). Higher lymph node yield in central neck dissection was not associated with higher incidental parathyroidectomy rates (odds ratio 1.13, 95% confidence interval 0.85–8.81, P = .82).ConclusionHigher surgical volume conferred a lower rate of incidental parathyroidectomy. Nonetheless, greater lymph node yield in central neck dissections did not result in greater parathyroid-related morbidity. Such findings support the value of leveraging surgical volume to both optimize oncologic resection and minimize complication rates.     

Parathyroidectomy for patients with secondary hyperparathyroidism in a changing landscape for the management of end-stage renal disease

BackgroundThe landscape of patients with end-stage renal disease is changing with the increasing availability of kidney transplantation. In the near future, a less aggressive approach to treat secondary hyperparathyroidism might be beneficial. We report outcomes of parathyroidectomy for end-stage renal disease–related hyperparathyroidism comparing the outcomes of limited, subtotal, and total parathyroidectomy.MethodsWe performed a retrospective analysis of prospectively collected data. Patients were divided into 3 parathyroidectomy subgroups: limited (<3 glands removed), subtotal (3–3.5 glands), and total (4 glands) parathyroidectomy. Primary outcome was serum levels of parathyroid hormone. Secondary endpoints were serum levels of calcium, phosphate, and alkaline phosphatase, postoperative complications, and persistent or recurrent disease rates.ResultsIn total, 195 patients were included for analysis of whom 13.8% underwent limited parathyroidectomy, 46.7% subtotal parathyroidectomy, and 39.5% total parathyroidectomy. Preoperative parathyroid hormone levels (pg/mL) were 471 (210–868), 1,087 (627–1,795), and 1,070 (475–1,632) for the limited, subtotal, and total parathyroidectomy groups, respectively (P < .001). A decrease in serum parathyroid hormone was seen in all groups; however, postoperative levels remained greater in the limited parathyroidectomy group compared to the subtotal and total parathyroidectomy groups (P < .001). Serum calcium, phosphate, and alkaline phosphatase levels decreased in all groups to within the reference range. In the limited parathyroidectomy group, persistent disease and recurrence occurred more frequently (P = .02 and P = .07, respectively).ConclusionSubtotal parathyroidectomy is the optimal strategy in an era with an increasing availability of kidney transplantation and improved regimens of dialysis. In this changing practice, the approach to parathyroid surgery, however, might shift to a less aggressive and patient-tailored approach.     

Black patients are more likely to undergo parathyroidectomy for secondary hyperparathyroidism

BackgroundPrior studies have demonstrated racial disparities in the severity of secondary hyperparathyroidism among dialysis patients. Our primary objective was to study the racial and socioeconomic differences in the timing and likelihood of parathyroidectomy in patients with secondary hyperparathyroidism.MethodsWe used the United States Renal Data System to identify 634,428 adult (age ≥18) patients who were on maintenance dialysis between 2006 and 2016 with Medicare as their primary payor. Adjusted multivariable Cox regression was performed to quantify the differences in parathyroidectomy by race.ResultsOf this cohort, 27.3% (173,267) were of Black race. Compared to 15.4% of White patients, 23.1% of Black patients lived in a neighborhood that was below a predefined poverty level (P < .001). The cumulative incidence of parathyroidectomy at 10 years after dialysis initiation was 8.8% among Black patients compared to 4.3% among White patients (P < .001). On univariable analysis, Black patients were more likely to undergo parathyroidectomy (adjusted hazard ratio = 1.83; 95% confidence interval, 1.74–1.93). This association persisted after adjusting for age, sex, cause of end-stage renal disease, body mass index, comorbidities, dialysis modality, and poverty level (adjusted hazard ratio = 1.35; 95% confidence interval, 1.27–1.43). Therefore, patient characteristics and socioeconomic status explained 26% of the association between race and likelihood of parathyroidectomy.ConclusionBlack patients with secondary hyperparathyroidism due to end-stage renal disease are more likely to undergo parathyroidectomy with shorter intervals between dialysis initiation and parathyroidectomy. This association is only partially explained by patient characteristics and socioeconomic factors.     

Factores de riesgo de persistencia en pacientes con tratamiento quirúrgico de hiperparatiroidismo primario

IntroductionPrimary hyperparathyroidism is the third most common endocrine disease. The aim of our study was to determine long-term outcomes and risk factors for persistence in patients undergoing parathyroidectomy for primary hyperparathyroidism.MethodsRetrospective study including patients undergoing parathyroidectomy between 2009- 2019. Cure was defined as reestablishment of normal calcium homeostasis lasting a minimum of 6 months. Persistence was defined by ongoing hypercalcemia more than 6 months after surgery. Recurrent PHTP was defined by recurrence of hypercalcemia after a normocalcemic interval at more than 6 months after surgery. A more detailed analysis was performed on patients with normocalcemia and persistently elevated PTH levels after surgery. Variables independently related to persistence were analyzed by multivariate analysis.ResultsWe included 212 patients. Mean age was 59 years and 83% were women. Cure was observed in 204 patients (96.2%), persistence in 8 (3.8%) and recurrence in 3 (1.4%). Four patients (1.9%) presented normocalcemia and persistently elevated PTH after surgery. All presented parathyroid pathology (2 adenomas and 2 hyperplasia). In follow-up we observed that adenoma subgroup presented one patient with CKD and one with vitamin D deficiency while in the hyperplasia subgroup two patients presented CKD. Persistence was independently associated with hyperplasia (Odds ratio=12.6, IC95%=1.28-124, p=0.030) and normal parathyroid tissue (Odds ratio=188, IC95%=9.33-379, p=0.001) on histopathological report.ConclusiónPrimary hyperparathyroidism is a safe procedure in terms of morbidity and long-term outcomes. Hyperplasia and normal parathyroid tissue on histopathological report are risk factors for persistence. An interdisciplinary diagnostic and therapeutic approach is required to prevent persistence.     

Undertreatment of primary hyperparathyroidism in a privately insured US population: Decreasing utilization of parathyroidectomy despite expanding surgical guidelines

BackgroundPrimary hyperparathyroidism is associated with substantial morbidity, including osteoporosis, nephrolithiasis, and chronic kidney disease. Parathyroidectomy can prevent these sequelae but is poorly utilized in many practice settings.MethodsWe performed a retrospective cohort study using the national Optum de-identified Clinformatics Data Mart Database. We identified patients aged ≥35 with a first observed primary hyperparathyroidism diagnosis from 2004 to 2016. Multivariable logistic regression was used to determine patient/provider characteristics associated with parathyroidectomy.ResultsOf 26,522 patients with primary hyperparathyroidism, 10,101 (38.1%) underwent parathyroidectomy. Of the 14,896 patients with any operative indication, 5,791 (38.9%) underwent parathyroidectomy. Over time, there was a decreasing trend in the rate of parathyroidectomy overall (2004: 54.4% to 2016: 32.4%, P < .001) and among groups with and without an operative indication. On multivariable analysis, increasing age and comorbidities were strongly, inversely associated with parathyroidectomy (age 75–84, odds ratio 0.50 [95% confidence interval 0.45–0.55]; age ≥85, odds ratio 0.21 [95% confidence interval 0.17–0.26] vs age 35–49; Charlson Comorbidity Index ≥2 vs 0 odds ratio 0.62 [95% confidence interval 0.58–0.66]).ConclusionThe majority of US privately insured patients with primary hyperparathyroidism are not treated with parathyroidectomy. Having an operative indication only modestly increases the likelihood of parathyroidectomy. Further research is needed to address barriers to treatment and the gap between guidelines and clinical care in primary hyperparathyroidism.     

Subtotal parathyroidectomy for primary chief cell hyperplasia of the multiple endocrine neoplasia type I syndrome.

To evaluate the efficacy of subtotal parathyroidectomy (STP) in the treatment of primary hyperparathyroidism due to multiple gland disease, 12 patients with multiple endocrine neoplasia (MEN) type I syndrome were reviewed out of 132 patients undergoing parathyroidectomy. Each patient had yearly follow-up examinations and calcium determinations for a minimum of four years except for one patient who died one year after S.T.P. Permanent hypoparathyroidism occurred in three patients. Two patients remained persistently hypercalcemic, and two patients developed recurrent hypercalcemia. One patient required oral administration of calcium and vitamin D for ten years following STP before recurrent hypercalcemia developed. Another patient was normocalcemic for three years before recurrent hypercalcemia was noted. Only five of these 12 patients remain normocalcemic without need of calcium and vitamin D therapy. In patients with MEN type I, the long-term results of STP are less than satisfactory. Not only is it difficult to gauge how viable parathyroid tissue must be left to prevent both permanent hypoparathyroidism and persistent hyperparathyroidism but there is also a long-term risk of recurrence.     

Total parathyroidectomy versus total parathyroidectomy with autotransplantation for secondary hyperparathyroidism: systematic review and meta-analysis

Background: Total parathyroidectomy (tPTX) and total parathyroidectomy with autotransplantation (tPTX?+?AT) are effective and inexpensive treatments for secondary hyperparathyroidism (sHPT), but we do not know which one is the optimal approach. Therefore, we undertook a meta-analysis to compare the safety and efficacy of these two surgical procedures.

Methodology: Studies published in English on PubMed, Embase and the Cochrane Library from inception to 27 September 2016 were searched systematically. Eligible studies comparing tPTX with tPTX?+?AT for sHPT were included and Review Manager v5.3 was used.

Results: Eleven studies were included in this meta-analysis. Ten cohort studies and one randomized controlled trial (RCT) involving 1108 patients with sHPT were identified. There was no significant difference in the prevalence of surgical complications (relative risk [RR], 1.71; 95% confidence interval [CI], 0.77–3.79; p?=?.19), all-cause mortality (RR, 0.68; 95% CI, 0.33–1.39; p?=?.29), sHPT persistence (RR, 3.81; 95% CI, 0.56–25.95; p?=?.17) or symptomatic improvement (RR, 1.02; 95% CI, 0.91–1.13; p?=?.79). tPTX could reduce the risk of sHPT recurrence (RR, 0.19; 95% CI, 0.09–0.41; p?p?=?.01) compared with tPTX?+?AT. Simultaneously, tPTX increased the risk of hypoparathyroidism (RR, 2.63; 95% CI, 1.06–6.51; p?=?.04).

Conclusions: We found tPTX and tPTX?+?AT to be useful methods for sHPT treatment. tPTX was superior for reducing the risk of sHPT recurrence and reoperation than tPTX?+?AT but, due to a lack of high statistical-power RCTs, comparative studies will be needed in the future.     

Predicting endocrine function after total pancreatectomy and islet cell autotransplantation: A novel approach utilizing computed tomography texture analysis

BackgroundIslet cell autotransplantation is an effective method to prevent morbidity associated with type IIIc diabetes after total pancreatectomy. However, there is no valid method to predict long-term endocrine function. Our aim was to assess computed tomography texture analysis as a strategy to predict long-term endocrine function after total pancreatectomy and islet cell autotransplantation.MethodsAll patients undergoing total pancreatectomy and islet cell autotransplantation from 2007 to 2020 who had high-quality preoperative computed tomography imaging available for texture analysis were included. The primary outcome was optimal long-term endocrine function, defined as stable glycemic control with <10 units of insulin/day.ResultsSixty-three patients met inclusion criteria. Median yield was 6,111 islet equivalent/kg body weight. At a median follow-up of 64.2 months, 12.7% (n = 8) of patients were insulin independent and 39.7% (n = 25) demonstrated optimal endocrine function. Neither total islet equivalent nor islet equivalent/kg body weight alone were associated with optimal endocrine function. To improve endocrine function prediction, computed tomography texture analysis parameters were analyzed, identifying an association between kurtosis (odds ratio, 2.32; 95% confidence interval, 1.08–4.80; P = .02) and optimal endocrine function. Sensitivity analysis discovered a cutoff for kurtosis = 0.60, with optimal endocrine function seen in 66.7% with kurtosis ≥0.60, compared with only 26.2% with kurtosis <0.60 (P < .01). On multivariate logistic regression including islet equivalent yield, only kurtosis ≥0.60 (odds ratio, 5.61; 95% confidence interval, 1.56–20.19; P = .01) and fewer small islet equivalent (odds ratio, 1.00; 95% confidence interval, 1.00–1.00; P = .02) were associated with optimal endocrine function, with the whole model demonstrating excellent prediction of long-term endocrine function (area under the curve, 0.775).ConclusionComputed tomography texture analysis can provide qualitative data, that when used in combination with quantitative islet equivalent yield, can accurately predict long-term endocrine function after total pancreatectomy and islet cell autotransplantation.     

Duct stenting versus modified Blalock–Taussig shunt in neonates and infants with duct-dependent pulmonary blood flow: A systematic review and meta-analysis

ObjectiveThe aim of this systematic review and meta-analysis is to evaluate whether duct stenting is associated with better survival and other clinical outcomes compared with the modified Blalock–Taussig shunt in infants with duct-dependent pulmonary flow.MethodsA systematic search of the Medline, Embase, and Cochrane databases was performed by 4 independent reviewers from inception to March 2019. Meta-analysis was performed using the DerSimonian and Laird method with inverse-variance weighting. The quality of evidence was summarized using the Grading of Recommendations, Assessment, Development, and Evaluation framework.ResultsSix comparative observational studies were included, of which 3 were rated low risk of bias. There was no difference in 30-day mortality between the Blalock–Taussig shunt and duct stenting groups (risk ratio, 1.02; 95% confidence interval, 0.46-2.27; P = .96; I² = 0%). However, there was benefit in favor of duct stenting for medium-term mortality (risk ratio, 0.63; 95% confidence interval, 0.40-0.99; P = .05; I² = 0%). Duct stenting demonstrated a reduced risk for procedural complications compared with the Blalock–Taussig shunt (risk ratio, 0.50; 95% confidence interval, 0.31-0.81; P = .005; I² = 0%). However, there was an increased risk for unplanned reintervention for duct stenting (risk ratio, 1.77; 95% confidence interval, 1.39-2.26; P < .00001; I² = 10%). Duct stenting demonstrated shorter mean intensive care unit length of stay (mean difference, ?4.69 days; 95% confidence interval, ?7.30 to ?2.07; P = .0004; I² = 80%), as well as shorter hospital length of stay (mean difference, ?5.78 days; 95% confidence interval, ?9.27 to ?2.28; P = .0009, I² = 75%). The overall quality of evidence was rated low using the Grading of Recommendations, Assessment, Development, and Evaluation framework.ConclusionsDuct stenting demonstrated comparable early mortality, lower medium-term mortality, lower risk of procedural complications, and higher risk of reintervention compared with the Blalock–Taussig shunt.     

Disparities in Time to Surgeon Evaluation Among Patients with Primary Hyperparathyroidism

BackgroundA majority of patients with primary hyperparathyroidism are not referred for surgical evaluation. We hypothesized that disparities in the rate of surgeon evaluation by language, race and ethnicity, and insurance contribute to this deficit.MethodsWe queried our institutional electronic health record registry for patients with first-incident hypercalcemia between 2010 and 2018 and subsequent biochemical diagnosis of primary hyperparathyroidism. We used the Kaplan-Meier method and Cox proportional hazards modeling to investigate estimated time to surgeon evaluation by language, race and ethnicity, and insurance status.ResultsOf 1,333 patients with a diagnosis of primary hyperparathyroidism, 74% were female, 67% were White, 44% were privately insured, and 88% preferred English. Fewer than one third (n = 377; 28%) were evaluated by a surgeon. After adjusting for demographic and clinical factors, Asian (hazard ratio = 0.38; 95% confidence interval, 0.18–0.84; P = .016) and Black or African American patients (hazard ratio = 0.59; 95% confidence interval, 0.39–0.90; P = .014) had a lower rate of surgeon evaluation compared to White patients. Although patients with Medicaid had a lower rate of surgeon evaluation compared to privately insured patients (hazard ratio = 0.52; 95% confidence interval, 0.35–0.77; P = .001), there was no difference in rate for those with Medicare or who were uninsured. Patients with non-English and non-Spanish language had a lower rate of evaluation compared to those who preferred English (hazard ratio = 0.47; 95% confidence interval, 0.23–0.98; P = .043).ConclusionRates of surgeon evaluation vary by race and ethnicity, insurance status, and preferred language. Evaluation of factors contributing to these disparities is needed to improve access to surgeon referral.     

Unilateral Clearance for Primary Hyperparathyroidism in Selected Patients with Multiple Endocrine Neoplasia Type 1

Background

Primary hyperparathyroidism is the most common manifestation of multiple endocrine neoplasia type 1 (MEN1). Guidelines advocate subtotal parathyroidectomy (STP) or total parathyroidectomy with autotransplantation due to high prevalence of multiglandular disease; however, both are associated with a significant risk of permanent hypoparathyroidism. More accurate imaging and use of intraoperative PTH levels may allow a less extensive initial parathyroidectomy (unilateral clearance, removing both parathyroids with cervical thymectomy) in selected MEN1 patients with primary hyperparathyroidism.

Methods

We performed a retrospective cohort study at a high-volume tertiary medical center including patients with MEN1 and primary hyperparathyroidism, who underwent STP or unilateral clearance as their initial surgery from 1995 to 2015. Unilateral clearance was offered to patients who had concordant sestamibi and ultrasound showing a single enlarged parathyroid gland. For both the groups, we compared rates of persistent/recurrent disease and permanent hypoparathyroidism.

Results

Eight patients had unilateral clearance and 16 had STP. Subtotal parathyroidectomy patients were younger (37 vs 52 years). One patient in each group had persistent disease. One (13 %) unilateral clearance and five (31 %) STP patients had recurrent hyperparathyroidism after a mean follow-up of 47 and 68 months (p = 0.62). No unilateral clearance patients and two of 16 SPT patients had permanent hypoparathyroidism (p = 0.54).

Conclusions

Some MEN1 patients with primary hyperparathyroidism who have concordant localizing studies may be selected for unilateral clearance as an alternative to STP. For appropriately selected MEN1 patients, unilateral clearance can achieve similar results as STP and has no risk of permanent hypoparathyroidism, and may facilitate possible future reoperations.

     

Muscle strength,physical performance,and metabolic changes after subtotal parathyroidectomy for secondary hyperparathyroidism

BackgroundHyperparathyroidism in patients on chronic hemodialysis presents with bone pain, pruritus, and extra-skeletal calcifications. Little attention has been paid to low plasma protein concentrations and muscle weakness in these patients. The present study was undertaken to characterize the impact of subtotal parathyroidectomy for chronic hemodialysis on body composition, muscle strength, plasma proteins, quality of life, and long-term clinical course.MethodsWe performed a prospective observational before-after assessment study of consecutive chronic hemodialysis patients referred for parathyroidectomy. Patients were investigated at baseline before parathyroidectomy and then at 1 and 6 months after surgery, with the aim to assess changes in metabolic parameters, body composition by bioimpedance, muscle strength, and quality of life (36-items Short Form Health Survey questionnaire). Follow-up was terminated when patients reached 1 of the 3 pre-defined end points: recurrence of secondary hyperparathyroidism, transplantation, or death.ResultsA group of 23 patients on hemodialysis were included. Preoperative handgrip strength was diminished by 52.4 ± 17%. After parathyroidectomy, a drop of immunoreactive parathyroid hormone concentrations (1,153 vs 237 pg/mL; P < .001) was observed together with increases in plasma protein (total: 6.8 vs7.8 g/dL, s-albumin 3.7 vs 4.4 g/dL and prealbumin: 31.7 vs 35.2 mg/dL; P < .001), handgrip strength (18.3 vs 22.9 kg: P = .001) as well as an improvement in physical dimension (32.9 vs 35.6; P = .004) and vitality (32.3 vs 47.1; P = .002) domains of the 36-items Short Form Health Survey questionnaire. After10 years, one-third of the patients had died, one-third of the patients had a recurrence of secondary hyperparathyroidism, and one-third of patients had received a kidney transplant and maintained a normal parathyroid function.ConclusionSubtotal parathyroidectomy improves protein metabolic markers, muscle strength, and physical performance in chronic hemodialysis patients.     

Risk factors for breast cancer mortality after ductal carcinoma in situ diagnosis differ from those for invasive recurrence

BackgroundBreast cancer mortality after ductal carcinoma in situ is rare, making it difficult to predict which patients are at risk and to identify whether risk factors for this outcome are the same as those for invasive recurrence. We aimed to identify whether risk factors for invasive recurrences are similar to those for breast cancer death after a diagnosis of pure ductal carcinoma in situ.MethodsThe Surveillance, Epidemiology, and End Results Program was queried for female patients diagnosed with pure ductal carcinoma in situ. Cumulative incidence was estimated by treatment group using competing risks. Competing risks regression was then performed for the development of in-breast invasive recurrence with competing risks of breast and non–breast cancer death. Competing risks regression was then again performed for development of breast cancer mortality with the competing risk of non–breast cancer death.ResultsA total of 29,515 patients were identified. Of them, 164 patients suffered breast cancer mortality without an intervening invasive recurrence, and 44 suffered breast cancer mortality after an invasive in-breast recurrence. On competing risks analysis for invasive in-breast recurrence, significant factors included lesion size >5 cm (hazard ratio = 1.59, 95% confidence interval 1.24–2.04, P < .001), diffuse disease (hazard ratio = 0.0005, 95% confidence interval 0.0003–0.0007, P < .001), other race (hazard ratio = 1.29, 95% confidence interval 1.10–1.52, P = .002), Black race (hazard ratio = 1.21, 95% confidence interval 1.01–1.46, P = .04), age at diagnosis (hazard ratio = 0.99, confidence interval 0.98–1.00, P = .02), low-grade disease (hazard ratio = 0.79, 95% confidence interval 0.64–0.96, P = .02), lumpectomy with radiation (hazard ratio = 0.67, 95% confidence interval 0.58-0.77, P < .001), and mastectomy (hazard ratio = 0.36, 95% confidence interval 0.30–0.44, P < .001). Significant factors for breast cancer mortality included age at diagnosis (hazard ratio = 1.04, 95% confidence interval 1.03–1.05, P < .001), Black race (hazard ratio = 2.88, 95% confidence interval 2.08–3.99, P < .001), diffuse disease (hazard ratio = 6.02, 95% confidence interval 1.39–26.07, P = .02), lumpectomy with radiation (hazard ratio = 0.51, 95% confidence interval 0.36–0.72, P < .001), and mastectomy (hazard ratio = 0.60, 95% confidence interval 0.50–0.92, P = .02).ConclusionOur results suggested that risk factors for in-breast invasive recurrence after a diagnosis of pure ductal carcinoma in situ differ from risk factors for breast cancer mortality and development of metastatic recurrence. In-breast invasive recurrence is not the only consideration for breast cancer specific mortality in ductal carcinoma in situ patients.     

Hyperparathyroidism at 1 year after kidney transplantation is associated with graft loss

BackgroundHyperparathyroidism persists in many patients after kidney transplantation. The purpose of this study was to evaluate the association between post-transplant hyperparathyroidism and kidney transplantation outcomes.MethodsWe identified 824 participants from a prospective longitudinal cohort of adult patients who underwent kidney transplantation at a single institution between December 2008 and February 2020. Parathyroid hormone levels before and after kidney transplantation were abstracted from medical records. Post-transplant hyperparathyroidism was defined as parathyroid hormone level ≥70 pg/mL 1 year after kidney transplantation. Cox proportional hazards models were used to estimate the adjusted hazard ratios of mortality and death-censored graft loss by post-transplant hyperparathyroidism. Models were adjusted for age, sex, race/ethnicity, college education, parathyroid hormone level before kidney transplantation, cause of kidney failure, and years on dialysis before kidney transplantation. A Wald test for interactions was used to evaluate the risk of death-censored graft loss by age, sex, and race.ResultsOf 824 recipients, 60.9% had post-transplant hyperparathyroidism. Compared with non-hyperparathyroidism patients, those with post-transplant hyperparathyroidism were more likely to be Black (47.2% vs 32.6%), undergo dialysis before kidney transplantation (86.9% vs 76.6%), and have a parathyroid hormone level ≥300 pg/mL before kidney transplantation (26.8% vs 9.5%) (all P < .001). Patients with post-transplant hyperparathyroidism had a 1.6-fold higher risk of death-censored graft loss (adjusted hazard ratio = 1.60, 95% confidence interval: 1.02–2.49) compared with those without post-transplant hyperparathyroidism. This risk more than doubled in those with parathyroid hormone ≥300 pg/mL 1 year after kidney transplantation (adjusted hazard ratio = 4.19, 95% confidence interval: 1.95–9.03). The risk of death-censored graft loss did not differ by age, sex, or race (all P_interaction > .05). There was no association between post-transplant hyperparathyroidism and mortality.ConclusionThe risk of graft loss was significantly higher among patients with post-transplant hyperparathyroidism when compared with patients without post-transplant hyperparathyroidism.     

Neuropsychologic changes in primary hyperparathyroidism after parathyroidectomy from a dual-institution prospective study

BackgroundThe impact of parathyroidectomy on neuropsychiatric symptoms in primary hyperparathyroidism remains poorly defined. The validated scales Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 can be used to assess depression and anxiety, respectively. Our aim was to prospectively characterize the changes in neuropsychiatric symptoms after parathyroidectomy.MethodsPatients undergoing parathyroidectomy and thyroidectomy (control) from two institutions between 2014 and 2019 were prospectively administered a questionnaire assessing neuropsychiatric symptoms before and after surgery. Paired t tests compared preoperative with postoperative neuropsychiatric symptoms and t tests compared differences in neuropsychiatric symptoms between parathyroidectomy and thyroidectomy.ResultsA total of 244 patients underwent parathyroidectomy and 161 underwent thyroidectomy. We observed improvement in neuropsychiatric symptoms after parathyroidectomy (6.2 [5.0–7.4], P < .01). Preoperatively, neuropsychiatric symptoms were more prevalent in patients undergoing parathyroidectomy when compared with thyroidectomy (11.2 ± 11.5 vs 7.5 ± 8.2, P < .01); however, after surgery there was no difference between the two groups (5.1 ± 7.1 vs 5.4 ± 7.2, P = .59). Preoperatively, 27.5% and 18.0% of patients endorsed moderate to severe depression and anxiety, which fell to 8.2% and 5.3%, respectively, (P < .01) after surgery.ConclusionPatients undergoing parathyroidectomy showed significant improvement in neuropsychiatric symptoms after surgery. Neuropsychiatric symptoms are more prevalent in patients with primary hyperparathyroidism. Neuropsychiatric symptoms should be assessed in all patients with primary hyperparathyroidism and should be considered a relative indication for parathyroidectomy.     

Safety and feasibility of esophagectomy following combined immunotherapy and chemoradiotherapy for esophageal cancer

ObjectivesWe sought to determine the safety and feasibility of esophagectomy after neoadjuvant immunotherapy and chemoradiotherapy in clinical trial patients with locally advanced esophageal cancer.MethodsWe retrospectively identified patients who were treated with neoadjuvant immunotherapy and chemoradiotherapy (n = 25) or chemoradiotherapy alone (n = 143) at our institution between 2017 and 2020. The primary end point was risk of 30-day major complications (Clavien-Dindo classification system grade ≥ 3), which was assessed between groups using a multivariable log-binomial regression model to obtain adjusted relative risk ratios. Secondary end points were interval to surgery, 30-day readmission rate, and 30-day mortality.ResultsAll included patients successfully completed neoadjuvant therapy and underwent esophagectomy with negative margins. Age, sex, performance status, clinical stage, histologic subtype, procedure type, and operative approach were similar between groups. Neoadjuvant immunotherapy was not associated with a statistically significantly increased risk of developing a major pulmonary (relative risk, 1.43; 95% confidence interval, 0.53-3.84; P = .5), anastomotic (relative risk, 1.34; 95% confidence interval, 0.45-3.94; P = .6), or other complication (relative risk, 1.29; 95% confidence interval, 0.26-6.28; P = .8). Median (interquartile range) interval to surgery was 54 days (47-61 days) in the immune checkpoint inhibitor group versus 53 days (47-66 days) in the control group (P = .6). Minimally invasive approaches were successful in 72% of cases, with only 1 conversion. Thirty-day mortality and readmission rates were 0% and 17%, respectively, in the immune checkpoint inhibitor group and 1.4% and 13%, respectively, in the control group.ConclusionsOn the basis of our preliminary experience, esophagectomy appears to be safe and feasible following combined neoadjuvant immunotherapy and standard chemoradiotherapy for locally advanced esophageal cancer.     

Parathyroid surgery in patients with renal failure.

A subtotal parathyroidectomy was performed in 32 patients with hyperparathyroidism and renal dysfunction. Minimal long-term sequelae were observed [two patients with recurrent hyperparathyroidism (6.2%), one patient with persistent hypoparathyroidism (3.1%)]. This experience is compared with reports in the literature advocating total parathyroidectomy and autotransplantation. A subtotal parathyroidectomy remains the preferred approach at this institution. Patients with elevated alkaline phosphatase levels before surgery should be monitored carefully for early postoperative hypocalcemia. The low incidence (3.2%) of hyperparathyroidism observed in patients following successful renal transplantation indicates that hypercalcemic allograft recipients should be observed for at least 4 months before contemplating surgical intervention.     

Phenotypes of primary hyperparathyroidism: Does parathyroidectomy improve clinical outcomes for all?

BackgroundPrimary hyperparathyroidism consists of 3 biochemical phenotypes: classic, normocalcemic, and normohormonal primary hyperparathyroidism. The clinical outcomes of patients with normocalcemic primary hyperparathyroidism and normohormonal primary hyperparathyroidism are not well described.MethodA retrospective review of patients who underwent parathyroidectomy at a single institution was performed. A logistical regression analysis of postoperative nephrolithiasis and highest percentage change in dual-energy x-ray absorptiometry scan comparison using Kruskal-Wallis test and Cox proportional hazard analysis of recurrence-free survival were performed.ResultsA total of 421 patients were included (340 classic, 39 normocalcemic primary hyperparathyroidism, 42 normohormonal primary hyperparathyroidism). Median follow-up was 8.8 months (range 0–126). Higher rates of multigland disease were seen in normocalcemic primary hyperparathyroidism (64.1%) and normohormonal primary hyperparathyroidism (56.1%) compared to the classic (25.8%), P < .001. There were no differences in postoperative complications. The largest percentage increases in bone mineral density at the first postoperative dual-energy x-ray absorptiometry scan were higher for classic (mean ± SD, 6.4 ± 9.1) and normocalcemic primary hyperparathyroidism (4.8 ± 11.9) compared to normohormonal primary hyperparathyroidism, which remained stable (0.2 ± 14.2). Normocalcemic primary hyperparathyroidism were more likely to experience nephrolithiasis postoperatively, 6/13 (46.2%) compared to 11/68 (16.2%) classic, and 2/13 (15.4%) normohormonal primary hyperparathyroidism, P = .0429. Normocalcemic primary hyperparathyroidism was the only univariate predictor of postoperative nephrolithiasis recurrence (odds ratio [95% confidence interval] 4.44 [1.25–15.77], P = .029). Normocalcemic primary hyperparathyroidism was significantly associated with persistent disease with 6/32 (18.8%) compared to 1/36 (2.8%) and 3/252 (1.2%) in normohormonal primary hyperparathyroidism and classic (P < .001).ConclusionThree phenotypes of primary hyperparathyroidism are distinct clinical entities. Normocalcemic primary hyperparathyroidism had higher incidence of persistent disease and postoperative nephrolithiasis but demonstrated improvements in postoperative bone density. These data should inform preoperative discussions with patients with normocalcemic primary hyperparathyroidism and normohormonal primary hyperparathyroidism regarding postoperative expectations.     

Effect of Cinacalcet in Kidney Transplant Patients With Hyperparathyroidism

ObjectiveIn dialysis patients, cinacalcet could be an effective alternative to parathyroidectomy for treating hyperparathyroidism. In the present study, we aimed to determine the characteristics of subjects with persistent hyperparathyroidism who require parathyroidectomy despite the use of cinacalcet.MethodsNine kidney transplant patients (7 men, 2 women; mean age 53.2 [SD, 8.9] years) who had tertiary hyperparathyroidism were reviewed in a single center. Pre- and postcinacalcet levels of calcium, phosphorous, intact parathyroid hormone (iPTH), and renal function were analyzed to evaluate the effect of cinacalcet treatment in these patients. The baseline parameters before cinacalcet treatment were compared in patients who did and did not undergo parathyroidectomy.ResultsCinacalcet reduced serum calcium levels in all patients (11.48 [SD, 0.73] mg/dL to 10.20 [0.70] mg/dL; P = .008). Serum phosphorous levels significantly increased from 2.28 (SD, 0.77) mg/dL to 3.02 (SD, 0.65) mg/dL (P = .03). The iPTH levels in 7 patients decreased, while the mean level remained unchanged in total subjects. The iPTH levels increased even with cinacalcet treatment in 2 patients. In 3 patients, serum calcium levels abruptly increased after cinacalcet withdrawal. Five patients who showed persistent hypercalcemia due to hyperparathyroidism underwent parathyroidectomy. These 5 patients had significantly different characteristics compared with 4 patients who did not undergo parathyroidectomy: hypercalcemia (11.92 [SD, 0.68] mg/dL vs 10.93 [SD, 0.26] mg/dL; P = .02), hypophosphatemia (1.74 [SD, 0.36] mg/dL vs 2.95 [SD, 0.58] mg/dL; P = .03), and hyperparathyroidism (252.2 [SD, 131.4] pg/dL vs 101.5 [SD, 18.4] pg/dL; P = .02).ConclusionCinacalcet reduced hypercalcemia due to hyperparathyroidism in the transplant patients. However, patients who had pre-existing higher iPTH, hypercalcemia, and hypophosphatemia needed parathyroidectomy. Therefore, cinacalcet could be considered an alternative to parathyroidectomy in selected patients.     

Ectopic and supernumerary parathyroid glands in patients with refractory renal hyperparathyroidism

BackgroundThe aims of this study were to determine the rate of ectopic and supernumerary parathyroid glands and the outcome of surgical therapy in patients with refractory renal hyperparathyroidism.Materials and MethodsA retrospective review of all patients who underwent parathyroidectomy for refractory renal hyperparathyroidism was completed. Operative and pathology reports were reviewed, and the number and location of resected parathyroid glands, patient outcomes, and follow-up were determined.ResultsDuring the period 1993–2019, a total of 68 patients underwent subtotal or total parathyroidectomy for renal hyperparathyroidism. Of those, 59 patients (87%) were on dialysis for an average of 6.7 years. We determined that 18 patients (26%) had 24 ectopic parathyroid glands, including 9 (13%) patients with 11 supernumerary glands. A total of 2 patients had a supernumerary gland in a normal anatomic location. Of the 24 ectopic glands, 14 (58%) were in the thymus. After parathyroidectomy, 4 patients (5.9%) had persistent hyperparathyroidism, 6 patients (8.8%) developed recurrent hyperparathyroidism, and 2 patients (3%) had permanent hypoparathyroidism.ConclusionEctopic and supernumerary parathyroid glands occurred in 26% and 16% of patients with renal hyperparathyroidism, respectively, and the thymus was the most common location. Thorough neck exploration and transcervical thymectomy are important to help reduce persistent and recurrent hyperparathyroidism after parathyroidectomy for renal hyperparathyroidism.