Abstract Background Thyroid cancer diagnoses are increasing and treatment can lead to significant morbidity. Long‐term health‐related quality of life (HRQoL) in thyroid cancer is understudied and lacks reference populations. This study compares long‐term HRQoL between patients with thyroid cancer or benign disease, following thyroid surgery. Methods Patients undergoing thyroidectomy between 2000 and 2017 were identified from a pathology database. 696 participants (278 malignant, 418 benign) were invited to complete a validated disease‐specific HRQoL tool, City of Hope—Thyroid Version. Propensity scores were used to adjust for demographic and clinical differences between cohorts. Results 206 patients (102 malignant, 104 benign), 71% female, returned surveys a median of 6.5 (range 1–19) years after thyroidectomy. Of the cancer cohort, 95% had differentiated thyroid cancer and 83% remained disease‐free. There were no significant differences in overall HRQoL scores between groups. In comparison to the benign cohort, cancer patients showed a significant detriment in the social subdomain score (OR 0.10–0.96, p = 0.017) but not in other subdomains (physical, psychological, spiritual). Female gender, increasing BMI and cancer recurrence were significantly associated with decreased overall HRQoL. Compared to the benign cohort, cancer patients reported more personal and family distress associated with diagnosis and treatment, increased future uncertainty, poorer concentration and greater financial burden. Conclusion Although no difference in overall HRQoL was found between patients undergoing thyroidectomy for benign or malignant disease, detriments in social well‐being may persist many years after surgery. Thyroid cancer patients and their families may benefit from increased supports around the time of diagnosis and treatment.
Summary Context TERT promoter mutations have been associated with adverse prognosis in papillary thyroid carcinomas ( PTC s). Objective We investigated the association between TERT promoter mutations and survival from PTC . Design Retrospective observational cohort study. Patients Eighty consecutive patients with PTC who underwent surgery between 1990 and 2003. Measurements TERT promoter was genotyped in DNA from 80 archival PTC s by Sanger sequencing. Median follow‐up was 106 months (range 1–270). Outcomes analysis was stratified according to disease and overall survival status. For each parameter, relative risk ( RR ) adjusted for age at first surgery and gender was estimated. Both univariate and multivariate analyses were performed using logistic regression, Kaplan–Meier survival analysis and Cox regression models. Results PTC s from 11 patients (14%) contained either C228T or C250T TERT promoter mutation. TERT mutations were significantly associated with adverse prognostic features such as older age ( P = 0·002), male gender ( P = 0·01) and Stage IV disease ( P = 0·03). Four patients died from PTC during follow‐up: 3 patients with TERT mutations (27%) and one without (1·5%). Disease‐related mortality rate with or without TERT mutations was 33·7 vs 1·6 per 1000 patient‐years respectively, that is 10 (95% CI = 1·0–104·1, P = 0·05) fold higher, after adjustment for age at first surgery and gender. The combination of TERT promoter mutation and BRAF V 600E significantly increased disease‐related death risk ( P = 0·002). TERT mutations increased expression of a reporter gene in thyroid cells containing BRAF V 600E . Conclusions TERT promoter mutations are a major indicator of death due to PTC s. Conversely, absence of TERT mutations portends better survival.
Individualized management, incorporating papillary thyroid cancer (PTC) variant-specific risk, is conceivably a useful treatment strategy for PTC, which awaits comprehensive data demonstrating differential risks of PTC variants to support.This study sought to establish the differential clinicopathological risk of major PTC variants: conventional PTC (CPTC), follicular-variant PTC (FVPTC), and tall-cell PTC (TCPTC).This was a retrospective study of clinicopathological outcomes of 6282 PTC patients (4799 females and 1483 males) from 26 centers and The Cancer Genome Atlas in 14 countries with a median age of 44 years (interquartile range, 33-56 y) and median follow-up time of 37 months (interquartile range, 15-82 mo).The cohort consisted of 4702 (74.8%) patients with CPTC, 1126 (17.9%) with FVPTC, and 239 (3.8%) with TCPTC. The prevalence of high-risk parameters was significantly different among the three variants, including extrathyroidal invasion, lymph node metastasis, stages III/IV, disease recurrence, mortality, and the use (need) of radioiodine treatment (all P < .001), being highest in TCPTC, lowest in FVPTC, and intermediate in CPTC, following an order of TCPTC > CPTC ≫ FVPTC. Recurrence and mortality in TCPTC, CPTC, and FVPTC were 27.3 and 6.7%, 16.1 and 2.5%, and 9.1 and 0.6%, corresponding to events per 1000 person-years (95% confidence interval [CI]) of 92.47 (64.66-132.26) and 24.61 (12.31-49.21), 34.46 (30.71-38.66), and 5.87 (4.37-7.88), and 24.73 (18.34-33.35) and 1.68 (0.54-5.21), respectively. Mortality hazard ratios of CPTC and TCPTC over FVPTC were 3.44 (95% CI, 1.07-11.11) and 14.96 (95% CI, 3.93-56.89), respectively. Kaplan-Meier survival analyses showed the best prognosis in FVPTC, worst in TCPTC, and intermediate in CPTC in disease recurrence-free probability and disease-specific patient survival. This was particularly the case in patients at least 45 years old.This large multicenter study demonstrates differential prognostic risks of the three major PTC variants and establishes a unique risk order of TCPTC > CPTC ≫ FVPTC, providing important clinical implications for specific variant-based management of PTC.
Surgical treatment for primary hyperparathyroidism (PHPT) has traditionally prioritized "bones and stones" over "moans and groans". As widespread routine biochemical testing and screening for osteoporosis becomes commonplace, more patients with "asymptomatic" or "minimally symptomatic" disease are being diagnosed. Strong indications for surgery remain confined to young patients and those with established osteoporosis or renal calculi.1 There remains some reluctance to refer patients for surgery where disease is "asymptomatic" particularly in those aged >50 years.2 Current guidelines focus on biochemical cure and longer-term improvements in bone mineral density and reduction in renal calculi as measures of success following surgery.1 From the patient perspective, the most concerning symptoms are often the "nonspecific symptoms" of PHPT. These include anxiety, depression, fatigue, cognitive decline, aches, and pains. Improvements in these "nonspecific symptoms" are well-documented following surgery and can be measured by both validated disease-specific patient-reported outcome measures (PROMs) and correlated with global health-related quality of life scores.3 As clinicians, it is difficult to predict the degree to which any individual patient will benefit from surgery particularly regarding neurocognitive symptoms. Why one patient bounds back into the clinic after surgery and another is disappointed at the lack of improvement in symptoms is not fully understood. Longer-term data on neurocognitive symptom change and the development of neuropsychiatric diagnoses after parathyroidectomy is lacking. In this manuscript, Song and colleagues investigate the effect of parathyroidectomy on the subsequent diagnosis of neuropsychiatric disorders.4 The study population is a large retrospective cohort of 3728 patients from their institutional database, encompassing health data from a population of over one million individuals. Notably, individuals with both "classical PHPT" (with elevation of both serum calcium and PTH) and "normohormonal PHPT" (elevation of serum calcium with normal PTH) are included. Normocalcemic patients and those with secondary causes of hyperparathyroidism are excluded. Just under half of the patients received surgery. Baseline differences in age, race, marital status, and PTH levels between the nonoperative and operative groups suggest some bias in surgical selection. Propensity score matching has been used to adjust for these potential confounders. At a median of 4.2 years follow-up, there was a significantly lower rate of new diagnoses of cognitive impairment, somnolence, and schizophrenia in the operative group. Diagnoses of anxiety, depression, and suicidal ideation were not influenced by operative management. In addition, a decreased likelihood of needing future hospitalization for neuropsychiatric disorders was found in those who underwent parathyroidectomy. The authors are to be congratulated on putting together such a large dataset investigating this important question. Steps have been taken to ensure the completeness of the data; reporting only a 3.4% loss to follow-up. The authors have been open about the limitations of their research and measured in their conclusions. Unlike prior studies on this topic that have utilized PROMs, the outcome measure in this study involves a neuropsychiatric diagnosis. No threshold for "diagnosis" is given, but it is probable that only those who sought health care for neuropsychiatric symptoms severe enough to warrant a "diagnosis" are included in this study. Thus, although the subtleties of the patient experience (including less prominent anxiety and depressive symptoms) are unlikely to be captured, this study brings us data about healthcare utilization for neuropsychiatric symptoms including hospitalization. The suggestion that parathyroidectomy might prevent or delay future neuropsychiatric disorders is persuasive. Further prospective data are required to confirm this association, establish causation, and identify those subsets of patients who are most likely to benefit. Nevertheless, this study brings to the evidence base tantalizing data indicating a possible role in neuropsychiatric health prevention (or preservation) with parathyroidectomy. This is likely to be an attractive proposition to many patients and their physicians and suggests that the indications for parathyroidectomy in "asymptomatic PHPT" be expanded. This is consistent with evolving modern surgical practice, including the recent Australian and New Zealand guidelines advocating for surgery in any patient with PHPT and an expected life expectancy of >10 years.5 For many years, endocrine surgeons have argued that "asymptomatic PHPT" is not truly asymptomatic and that surgery should be considered in all patients fit for anesthesia. This manuscript suggests that we move a little further beyond this notion, and turn our focus to the role of parathyroidectomy in preventing future health morbidity (physical and psychological), to the longer term benefit of both our patients and the health system. Open access publishing facilitated by The University of Newcastle, as part of the Wiley - The University of Newcastle agreement via the Council of Australian University Librarians. Christine J. O'Neill: Conceptualization; writing—original draft; writing—review & editing.
Evidence from experimental studies suggests that PTH has a regulatory influence on renal perfusion, glomerular filtration rate and mesangial cell function. Decline in renal function following parathyroidectomy has been demonstrated in some renal transplant recipients. The impact of parathyroidectomy on residual kidney functions in non-transplant chronic kidney disease (CKD) is unclear. We hypothesised parathyroidectomy in patients with CKD could accelerate GFR decline which may or may not recover to baseline.
Pathogenic ALK translocations have been reported in papillary thyroid carcinoma (PTC). We developed and validated a screening algorithm based on immunohistochemistry (IHC), followed by fluorescence in situ hybridization (FISH) in IHC-positive cases to identify ALK-rearranged PTC. IHC and FISH were performed in a cohort of 259 thyroid carcinomas enriched for aggressive variants. IHC was positive in 8 cases, 6 confirmed translocated by FISH (specificity 75%). All 251 IHC-negative cases were FISH negative (sensitivity 100%). Having validated this approach, we performed screening IHC, followed by FISH in IHC-positive cases in an expanded cohort. ALK translocations were identified in 11 of 498 (2.2%) of all consecutive unselected PTCs and 3 of 23 (13%) patients with diffuse sclerosing variant PTCs. No ALK translocations were identified in 36 PTCs with distant metastases, 28 poorly differentiated (insular) carcinomas, and 20 anaplastic carcinomas. All 14 patients with ALK translocations were female (P=0.0425), and translocations occurred at a younger age (mean 38 vs. 48 y, P=0.0289 in unselected patients). ALK translocation was an early clonal event present in all neoplastic cells and mutually exclusive with BRAF mutation. ALK translocation was not associated with aggressive clinicopathologic features (size, stage, metastasis, vascular invasion, extrathyroidal extension, multifocality, risk for recurrence, radioiodine resistance). We conclude that 2.2% of PTCs are ALK-translocated and can be identified by screening IHC followed by FISH. ALK translocations may be more common in young females and diffuse sclerosing variant PTC but do not connote more aggressive disease.
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