Thyroid Incidentalomas: Incidence and Oncological Implication in Patients with Esophageal Cancer.

INTRODUCTION: Thyroid incidentalomas are often encountered during imaging performed for the workup of esophageal cancer. Their oncological significance is unknown. This study aimed to establish incidence and etiology of thyroid incidentalomas found during the diagnostic workup of esophageal cancer. METHODS: All esophageal cancer patients referred to or diagnosed at the Amsterdam UMC between January 2012 and December 2016 were included. Radiology and multidisciplinary team meeting reports were reviewed for presence of thyroid incidentalomas. When present, the fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG-PET/CT) or CT was reassessed by a radiologist. Primary outcome was the incidence and etiology of thyroid incidentalomas. RESULTS: In total, 1,110 esophageal cancer patients were included. Median age was 66 years, most were male (77.2%) and had an adenocarcinoma (69.4%). For 115 patients (10.4%), a thyroid incidentaloma was reported. Two thyroidal lesions proved malignant. One was an esophageal cancer metastasis (0.9%) and one was a primary thyroid carcinoma (0.9%). Only the primary thyroid carcinoma resulted in treatment alteration. The other malignant thyroid incidentaloma was in the context of disseminated esophageal disease and ineligible for curative treatment. CONCLUSION: In this study, thyroid incidentalomas were only very rarely oncologically significant. Further etiological examination should only be considered in accordance with the TI-RADS classification system and when clinical consequences are to be expected.

International Validation of a Nomogram to Predict Recurrence after Resection of Grade 1 and 2 Nonfunctioning Pancreatic Neuroendocrine Tumors.

BACKGROUND: Despite the low recurrence rate of resected nonfunctional pancreatic neuroendocrine tumors (NF-pNETs), nearly all patients undergo long-term surveillance. A prediction model for recurrence may help select patients for less intensive surveillance or identify patients for adjuvant therapy. The objective of this study was to assess the external validity of a recently published model predicting recurrence within 5 years after surgery for NF-pNET in an international cohort. This prediction model includes tumor grade, lymph node status and perineural invasion as predictors. METHODS: Retrospectively, data were collected from 7 international referral centers on patients who underwent resection for a grade 1-2 NF-pNET between 1992 and 2018. Model performance was evaluated by calibration statistics, Harrel's C-statistic, and area under the curve (AUC) of the receiver operating characteristic curve for 5-year recurrence-free survival (RFS). A sub-analysis was performed in pNETs >2 cm. The model was improved to stratify patients into 3 risk groups (low, medium, high) for recurrence. RESULTS: Overall, 342 patients were included in the validation cohort with a 5-year RFS of 83% (95% confidence interval [CI]: 78-88%). Fifty-eight patients (17%) developed a recurrence. Calibration showed an intercept of 0 and a slope of 0.74. The C-statistic was 0.77 (95% CI: 0.70-0.83), and the AUC for the prediction of 5-year RFS was 0.74. The prediction model had a better performance in tumors >2 cm (C-statistic 0.80). CONCLUSIONS: External validity of this prediction model for recurrence after curative surgery for grade 1-2 NF-pNET showed accurate overall performance using 3 easily accessible parameters. This model is available via www.pancreascalculator.com.

Preoperative metabolic classification of thyroid nodules using mass spectrometry imaging of fine-needle aspiration biopsies.

Thyroid neoplasia is common and requires appropriate clinical workup with imaging and fine-needle aspiration (FNA) biopsy to evaluate for cancer. Yet, up to 20% of thyroid nodule FNA biopsies will be indeterminate in diagnosis based on cytological evaluation. Genomic approaches to characterize the malignant potential of nodules showed initial promise but have provided only modest improvement in diagnosis. Here, we describe a method using metabolic analysis by desorption electrospray ionization mass spectrometry (DESI-MS) imaging for direct analysis and diagnosis of follicular cell-derived neoplasia tissues and FNA biopsies. DESI-MS was used to analyze 178 tissue samples to determine the molecular signatures of normal, benign follicular adenoma (FTA), and malignant follicular carcinoma (FTC) and papillary carcinoma (PTC) thyroid tissues. Statistical classifiers, including benign thyroid versus PTC and benign thyroid versus FTC, were built and validated with 114,125 mass spectra, with accuracy assessed in correlation with clinical pathology. Clinical FNA smears were prospectively collected and analyzed using DESI-MS imaging, and the performance of the statistical classifiers was tested with 69 prospectively collected clinical FNA smears. High performance was achieved for both models when predicting on the FNA test set, which included 24 nodules with indeterminate preoperative cytology, with accuracies of 93% and 89%. Our results strongly suggest that DESI-MS imaging is a valuable technology for identification of malignant potential of thyroid nodules.

A Novel and Generic Workflow of Indocyanine Green Perfusion Assessment Integrating Standardization and Quantification Toward Clinical Implementation.

OBJECTIVE: This study aims to generate a reproducible and generalizable Workflow model of ICG-angiography integrating Standardization and Quantification (WISQ) that can be applied uniformly within the surgical innovation realm independent of the user. SUMMARY BACKGROUND DATA: Tissue perfusion based on indocyanine green (ICG)-angiography is a rapidly growing application in surgical innovation. Interpretation of results has been subjective and error-prone due to the lack of a standardized and quantitative ICG-workflow and analytical methodology. There is a clinical need for a more generic, reproducible, and quantitative ICG perfusion model for objective assessment of tissue perfusion. METHODS: In this multicenter, proof-of-concept study, we present a generic and reproducible ICG-workflow integrating standardization and quantification for perfusion assessment. To evaluate our model's clinical feasibility and reproducibility, we assessed the viability of parathyroid glands after performing thyroidectomy. Biochemical hypoparathyroidism was used as the postoperative endpoint and its correlation with ICG quantification intraoperatively. Parathyroid gland is an ideal model as parathyroid function post-surgery is only affected by perfusion. RESULTS: We show that visual subjective interpretation of ICG-angiography by experienced surgeons on parathyroid perfusion cannot reliably predict organ function impairment postoperatively, emphasizing the importance of an ICG quantification model. WISQ was able to standardize and quantify ICG-angiography and provided a robust and reproducible perfusion curve analysis. A low ingress slope of the perfusion curve combined with a compromised egress slope was indicative for parathyroid organ dysfunction in 100% of the cases. CONCLUSION: WISQ needs prospective validation in larger series and may eventually support clinical decision-making to predict and prevent postoperative organ function impairment in a large and varied surgical population.

Value of Laparoscopy for Resection of Small-Bowel Neuroendocrine Neoplasms Including Central Mesenteric Lymphadenectomy.

BACKGROUND: Literature on laparoscopic resection of small-bowel neuroendocrine neoplasms consists of single case descriptions or small selected case-series only, likely because of challenging mesenteric lymphadenectomy. OBJECTIVE: We evaluated an institutional change in approach from open to laparoscopic resection of small-bowel neuroendocrine neoplasm independent from lymph node involvement. DESIGN: This is a retrospective comparative cohort study. SETTING: This study was conducted at a tertiary referral center. PATIENTS: Patients with small-bowel neuroendocrine neoplasms were included. INTERVENTIONS: Laparoscopic or open segmental bowel resection with central mesenteric lymphadenectomy was the studied intervention. MAIN OUTCOME MEASURES: Complexity of lymphadenectomy was assessed by determining the distance between suspect lymph nodes and main mesenteric branches on preoperative CT. Number of (tumor-positive) lymph nodes, conversion to open surgery, and postoperative complications according to Clavien-Dindo classification and length of stay were measured. RESULTS: A total of 34 patients were identified, of whom 11 (32%) underwent open and 23 (68%) laparoscopic surgery. Distances between lymph nodes and main mesenteric branches and number of examined and tumor-positive lymph nodes did not differ significantly. Laparoscopy was converted in 7 patients (30%). Major postoperative complications (grades 3-5) occurred in 1 patient (9%) in the open surgery group (grade 5) and 2 patients (9%) in the laparoscopic surgery group (grade 3b). The length of stay was 8 days (range, 6-18 d) in the open surgery group and 4 days (4-8 d) in the laparoscopic group (p = 0.036). LIMITATIONS: Long-term outcomes could not reliably be assessed because of the relatively short follow-up time of the laparoscopy group. CONCLUSIONS: Laparoscopic bowel resection with central mesenteric lymphadenectomy for small-bowel neuroendocrine neoplasm appears safe and associated with similar pathologic outcome and shorter length of stay in the setting of a tertiary referral center. See Video Abstract at http://links.lww.com/DCR/B512. VALOR DE LA LAPAROSCOPIA PARA LA RESECCIN DE NEOPLASIAS NEUROENDOCRINAS DEL INTESTINO DELGADO, INCLUIDA LA LINFADENECTOMA MESENTRICA CENTRAL: ANTECEDENTES:La literatura sobre la resección laparoscópica de neoplasias neuroendocrinas del intestino delgado consiste en descripciones de casos únicos o en series de pequeños casos seleccionados, probablemente debido a la dificultad de la linfadenectomía mesentérica.OBJETIVO:Evaluamos un cambio institucional en el enfoque de la resección abierta a laparoscópica de SB-NEN independientemente de la afectación de los ganglios linfáticos.DISEÑO:Este es un estudio de cohorte comparativo retrospectivo.AJUSTE:Este estudio se realizó en un centro de referencia terciario.PACIENTES:Pacientes con neoplasias neuroendocrinas de intestino delgado.INTERVENCIONES:Resección intestinal segmentaria laparoscópica o abierta con linfadenectomía mesentérica central.PRINCIPALES MEDIDAS DE RESULTADO:La complejidad de la linfadenectomía se evaluó determinando la distancia entre los ganglios linfáticos sospechosos y las principales ramas mesentéricas en la TC preoperatoria. Número de ganglios linfáticos (tumor positivos), conversión a cirugía abierta, complicaciones postoperatorias según Clavien-Dindo y duración de la estancia.RESULTADOS:Se identificaron 34 pacientes, de los cuales 11 (32%) fueron sometidos a cirugía abierta y 23 (68%) laparoscópica. Las distancias entre los ganglios linfáticos y las principales ramas mesentéricas y el número de ganglios linfáticos examinados y con tumores positivos no difirieron significativamente. La laparoscopia se convirtió en 7 pacientes (30%). Se produjeron complicaciones posoperatorias importantes (grados 3-5) en un paciente (9%) en el grupo de cirugía abierta (grado 5) y en 2 (9%) pacientes en el grupo de cirugía laparoscópica (grado 3b). La estancia intrahospitalaria fue de 8 días (rango 6-18) en el grupo de cirugía abierta y 4 días (4-8) en el grupo laparoscópico (p = 0.036).LIMITACIONES:Los resultados a largo plazo no se pudieron evaluar de manera confiable debido al seguimiento relativamente corto del grupo de laparoscopia.CONCLUSIONES:La resección intestinal laparoscópica con linfadenectomía mesentérica central para SB-NEN parece segura y se asocia con un resultado patológico similar y una estadía más corta en el contexto de un centro de referencia terciario. Consulte Video Resumen en http://links.lww.com/DCR/B512.

Evaluating Nationwide Application of Minimally Invasive Surgery for Treatment of Small Bowel Neuroendocrine Neoplasms.

AIM: Open resection of small bowel neuroendocrine neoplasms (SB-NEN) is still considered standard-of-care, mainly because of frequently encountered multifocality and central mesenteric masses. The aim of this study was to evaluate surgical approach for SB-NEN at a national level and determine predictors for overall survival. METHODS: Patients with SB-NEN who underwent resection between 2005 and 2015 were included from the Netherlands Cancer Registry. Patient and tumor characteristics were compared between laparoscopic and open approach. Overall survival was assessed by Kaplan-Meier and compared with the Log-rank test. Independent predictors were determined by Cox proportional hazards model. RESULTS: In total, 482 patients were included, of whom 342 (71%) underwent open and 140 (29%) laparoscopic resection. The open resection group had significantly more multifocal tumors resected (24% vs. 14%), pN2 lymph nodes (18% vs. 7%) and stage IV disease (36% vs. 22%). Overall survival after open resection was significantly shorter compared to laparoscopic resection (3-year: 81% vs. 89%, 5-year: 71% vs. 84%, p = 0.004). In multivariable analysis, age above 60-years (60-75, HR 3.38 (95% CI 1.84-6.23); > 75 years, HR 7.63 (95% CI 3.86-15.07)), stage IV disease (HR 1.86 (95% CI 1.18-2.94)) and a laparoscopic approach (HR 0.51 (95% CI 0.28-0.94)) were independently associated with overall survival, whereas multifocal primary tumor, grade and resection margin status were not. CONCLUSION: Laparoscopic resection was the approach in 29% of SB-NEN at a national level with selection of the more favorable patients. Laparoscopic resection remained independently associated with better overall survival besides age and stage, but residual confounding cannot be excluded.

Update on Incidence, Prevalence, Treatment and Survival of Patients with Small Bowel Neuroendocrine Neoplasms in the Netherlands.

BACKGROUND: Small bowel neuroendocrine neoplasms (SB-NEN) are rare cancers, population-based studies are needed to study this rare indolent disease. The aim of this study was to explore trends in epidemiology, treatment and survival outcomes of patients with SB-NEN based on Dutch nationwide data. PATIENTS AND METHODS: Patients with grade 1 or 2 SB-NEN diagnosed between 2005 and 2015 were retrieved from the Netherlands Cancer Registry and linked to The Nationwide Network and Registry of Histo- and Cytopathology in the Netherlands. Age-adjusted incidence rates were calculated based using the direct standardization method. Survival analyses were performed with the Kaplan-Meier method. RESULTS: A total of 1132 patients were included for epidemiological analyses. The age-adjusted incidence rate of SB-NEN increased from 0.52 to 0.81 per 100.000 person-years between 2005 and 2015. Incidence was higher for males than females (0.93 vs. 0.69 in 2015). Most patients had grade 1 tumours (83%). Surgery was performed in 86% of patients, with resection of the primary tumour in 99%. During the study period, administration of somatostatin analogues (SSAs) increased from 5 to 22% for stage III and from 27 to 63% for stage IV disease. Mean follow-up was 61 (standard deviation 38) months. Survival data were complete for 975/1132 patients and five-year overall survival was 75% for stage I-II, 75% for stage III and 57% for stage IV. CONCLUSIONS: This study shows an increase in the incidence of SB-NEN in the Netherlands. A predominant role of surgery was found in all disease stages. Use of SSAs has increased over time.

Outcomes of parathyroidectomy versus calcimimetics for secondary hyperparathyroidism and kidney transplantation: a propensity-matched analysis.

PURPOSE: Calcimimetics are currently indicated for severe secondary hyperparathyroidism (SHPT). However, the role of parathyroidectomy (PTX) for these patients is still under debate, and its impact on subsequent kidney transplantation (KTX) is unclear. In this study, we compare the outcomes of kidney transplantation after PTX or medical treatment. METHODS: Patients who underwent KTX and had SHPT were analyzed retrospectively. Two groups were selected (patients who had either PTX or calcimimetics prior to KTX) using a propensity score for sex, age, donor type, and parathyroid hormone levels (PTH) during dialysis. The primary outcome was graft failure, and secondary outcomes were surgical KTX complications, survival, serum PTH, serum calcium, and serum phosphate levels post-KTX. RESULTS: Matching succeeded for 92 patients. After PTX, PTH was significantly lower on the day of KTX as well as at 1 and 3 years post-KTX (14.00 pmol/L (3.80-34.00) vs. 71.30 pmol/L (30.70-108.30), p < 0.01, 10.10 pmol/L (2.00-21.00) vs. 32.35 pmol/L (21.58-51.76), p < 0.01 and 13.00 pmol/L (6.00-16.60) vs. 19.25 pmol/L (13.03-31.88), p = 0.027, respectively). No significant differences in post-KTX calcium and phosphate levels were noted between groups. Severe KTX complications were more common in the calcimimetics group (56.5% vs. 30.4%, p = 0.047). There were no differences in 10-year graft failure and overall survival. CONCLUSION: PTX resulted in lower PTH after KTX in comparison to patients who received calcimimetics. Severe complications were more common after calcimimetics, but graft failure and overall survival were similar.

Timing of Parathyroidectomy Does Not Influence Renal Function After Kidney Transplantation.

BACKGROUND: Parathyroidectomy (PTx) is the treatment of choice for end-stage renal disease (ESRD) patients with therapy-resistant hyperparathyroidism (HPT). The optimal timing of PTx for ESRD-related HPT-before or after kidney transplantation (KTx)-is subject of debate. METHODS: Patients with ESRD-related HPT who underwent both PTx and KTx between 1994 and 2015 were included in a multicenter retrospective study in four university hospitals. Two groups were formed according to treatment sequence: PTx before KTx (PTxKTx) and PTx after KTx (KTxPTx). Primary endpoint was renal function (eGFR, CKD-EPI) between both groups at several time points post-transplantation. Correlation between the timing of PTx and KTx and the course of eGFR was assessed using generalized estimating equations (GEE). RESULTS: The PTxKTx group consisted of 102 (55.1%) and the KTxPTx group of 83 (44.9%) patients. Recipient age, donor type, PTx type, and pre-KTx PTH levels were significantly different between groups. At 5 years after transplantation, eGFR was similar in the PTxKTx group (eGFR 44.5 ± 4.0 ml/min/1.73 m2) and KTxPTx group (40.0 ± 6.4 ml/min/1.73 m2, p = 0.43). The unadjusted GEE model showed that timing of PTx was not correlated with graft function over time (mean difference -1.0 ml/min/1.73 m2, 95% confidence interval -8.4 to 6.4, p = 0.79). Adjustment for potential confounders including recipient age and sex, various donor characteristics, PTx type, and PTH levels did not materially influence the results. CONCLUSIONS: In this multicenter cohort study, timing of PTx before or after KTx does not independently impact graft function over time.

Safety and efficacy of subtotal or total parathyroidectomy for patients with secondary or tertiary hyperparathyroidism in four academic centers in the Netherlands.

PURPOSE: Hyperparathyroidism (HPT) is a common abnormality in patients with end-stage renal disease (ESRD). Since the introduction of cinacalcet in 2004, a shift from surgery toward predominantly medical treatment has occurred. Surgery is thought to be associated with more complications than oral medication. The aim of this retrospective study was to evaluate 30-day outcomes and effectiveness of parathyroidectomy (PTx) in ESRD patients in the Netherlands. METHODS: A national database containing data from four academic medical centers in the Netherlands of patients with ESRD-related HPT, who had undergone PTx and kidney transplantation between 1994 and 2015, was established. Primary endpoints were 30-day mortality and complication rate. Secondary endpoints were biochemical measurements. RESULTS: We identified 187 HPT patients undergoing PTx, with a median age of 46 years. Median preoperative PTH level was 866 pg/mL (interquartile range [IQR] 407-1547 pg/mL). At 3 months, the median PTH drop from baseline was 93% (IQR, 71-98%) to a median of 61 pg/mL (IQR, 23-148 pg/mL, p < 0.001). Over the 25-year inclusion period, 13 patients (7.0%) required re-exploration for persistent or recurrent disease. Thirty-day mortality and complication rate were 0.0% and 7.9% respectively. Median serum calcium levels improved significantly postoperatively from 2.6 (2.4-2.8) mmol/L to 2.3 (2.1-2.5) mmol/L (p < 0.001). CONCLUSIONS: PTx is a safe and effective procedure in the frail ESRD population. These data show that there should be no reluctance for surgical intervention and when indicated, nephrologists can safely refer these patients for PTx.

Impact of the Introduction of Calcimimetics on Timing of Parathyroidectomy in Secondary and Tertiary Hyperparathyroidism.

BACKGROUND: Hyperparathyroidism (HPT), both secondary and tertiary, is common in patients with end-stage renal disease, and is associated with severe bone disorders, cardiovascular complications, and increased mortality. Since the introduction of calcimimetics in 2004, treatment of HPT has shifted from surgery to predominantly medical therapy. OBJECTIVE: The aim of this study was to evaluate the impact of this change of management on the HPT patient population before undergoing (sub-)total parathyroidectomy (PTx). METHODS: Overall, 119 patients with secondary or tertiary HPT undergoing PTx were included in a retrospective, single-center cohort. Group A, who underwent PTx before January 2005, was compared with group B, who underwent PTx after January 2005. Patient characteristics, time interval between HPT diagnosis and PTx, and postoperative complications were compared. RESULTS: Group A comprised 70 (58.8 %) patients and group B comprised 49 (41.2 %) patients. The median interval between HPT diagnosis and PTx was 27 (interquartile range [IQR] 12.5-48.0) and 49 (IQR 21.0-75.0) months for group A and B, respectively (p = 0.007). Baseline characteristics were similar among both groups. The median preoperative serum parathyroid hormone (PTH) level was 936 pg/mL (IQR 600-1273) for group A versus 1091 pg/mL (IQR 482-1373) for group B (p = 0.38). PTx resulted in a dramatic PTH reduction (less than twofold the upper limit: A, 80.0 %; B, 85.4 %), and postoperative complication rates were low in both groups (A: 7.8 %; B: 10.2 %) [p = 0.66]. CONCLUSIONS: The introduction of calcimimetics in 2004 is associated with a significant 2-year delay of surgery with continuously elevated preoperative PTH levels, while parathyroid surgery, even in a fragile population, is considered a safe and effective procedure.

Effect of parathyroidectomy and cinacalcet on quality of life in patients with end-stage renal disease-related hyperparathyroidism: a systematic review.

BACKGROUND: Patients with end-stage renal disease (ESRD) have a decreased quality of life (QoL), which is attributable in part to ESRD-related hyperparathyroidism (HPT). Both cinacalcet and parathyroidectomy (PTx) are treatments for advanced HPT, but their effects on QoL are unclear. We performed a systematic review to evaluate the impact of cinacalcet and PTx on QoL. METHODS: A systematic literature search was performed using PubMed and EMBASE databases to identify relevant articles. The search was based on the following keywords: 'parathyroidectomy' or 'cinacalcet', 'secondary hyperparathyroidism' or 'renal hyperparathyroidism' combined with 'quality of life' or 'SF-36' or 'symptomatology'. Only studies reporting on QoL at baseline and during follow-up were included. QoL scores were extracted from the selected manuscripts and weighted means were calculated. Due to a lack of available data on QoL improvement in patients using cinacalcet, a meta-analysis could not be performed. RESULTS: In all, eight articles reached our inclusion criteria. Of this, five articles reported the effect of PTx on QoL. All PTx studies were observational and non-controlled. The physical component scores of the 36-item Medical Outcomes Study Short-Form Health Survey increased significantly with a weighted mean of 35.5% (P < 0.05). Mental component scores increased with 13.7% (P < 0.05). Parathyroidectomy assessment of symptom scores improved from 561 preoperatively to 302 postoperatively (-259 points; -46.2%). Visual analogue scale scores decreased significantly for skin itching (46.6%), joint pain (30.4%) and muscle weakness (28.7%) (P < 0.05). Three studies on the effect of cinacalcet on QoL were included, including one randomized controlled trial. None of these studies showed significant improvement of physical component and mental component scores. CONCLUSIONS: PTx improved QoL in patients treated for ESRD-related HPT, whereas cinacalcet did not. The difference in impact between PTx and cinacalcet on QoL has not been compared directly.

Impact of EDP-M on survival of patients with metastatic adrenocortical carcinoma: A population-based study.

INTRODUCTION: Historically, stage IV adrenocortical carcinoma (mACC) has a poor prognosis with a median overall survival (OS) of only 5 months. Based on the FIRM-ACT trial published in 2012, guidelines now advise first line systemic treatment with etoposide, cisplatin, doxorubicin and mitotane (EDP-M). The effect of EDP-M on patient survival in clinical practice in the Netherlands is unknown. METHODS: The data of all patients with mACC (2005-2020) were obtained from the Netherlands comprehensive cancer organization (IKNL). The effect of EDP-M on patient survival was assessed using Kaplan-Meier analysis and multivariate Cox regression analysis including clinical, therapy and tumor characteristics. RESULTS: In total 167 patients with mACC were included. For patients diagnosed from 2014 onwards, EDP-M (in 22 patients (22%)) lead to a numerically but not statistically significant improved OS compared to those not receiving EDP-M (11.8 vs 5.6 months, p = 0.525). For systemic treatments, patients treated with mitotane only had the best 5-year OS (11.4%, p = 0.006) regardless of year of diagnosis. In multivariate Cox regression analysis EPD-M was not associated with OS; palliative adrenalectomy (HR: 0.26, p = <.001) and local treatment of metastases (HR: 0.35, p = 0.001) were associated with a better OS and a primary tumor Ki-67 index > 20% (HR: 2.67, p = 0.003) with a worse OS from 2014 onwards. Patients diagnosed before 2014 had a significantly poorer OS compared to from 2014 onwards (5-yr: 4.5 vs 8.4%, OS: 6.8 vs 8.3 months, p = 0.032). CONCLUSION: OS for mACC in the Netherlands has improved in the last decade. Receiving EDP-M did not significantly improve OS for patients with mACC. The use of multimodality treatment including palliative adrenalectomy, mitotane and local treatment of (oligo-)metastases in appropriately selected patients has improved the OS for mACC patients since 2014.

Deescalating Follow-up After Hemithyroidectomy for Patients With Low-risk Papillary Thyroid Microcarcinoma.

Importance: Structural recurrent disease (RD) after surgical treatment of papillary thyroid microcarcinoma (mPTC) is rare. We hypothesized that the RD rate after hemithyroidectomy in low-risk patients with mPTC is low. Objective: To assess the occurrence of RD in Dutch patients with mPTC who received surgical treatment according to the Dutch guidelines. Design, Setting, and Participants: This nationwide retrospective cohort study included all patients who had undergone surgery with a diagnosis of cN0/cNx mPTC in the Netherlands between January 2000 and December 2020 were identified from the Netherlands Cancer Registry database. Patients with preoperative lymph node metastases were excluded. Two groups were defined: group 1 (incidental), mPTC in pathology report after thyroid surgery for another indication; and group 2 (nonincidental), patients with a preoperative highly suspect thyroid nodule (Bethesda 5) or proven mPTC (Bethesda 6). Dutch guidelines state that a hemithyroidectomy is sufficient in patients with unifocal, intrathyroidal mPTC. Main Outcomes and Measures: The occurrence of RD in patients with low-risk mPTC after hemithyroidectomy. Results: In total, 1636 patients with mPTC were included. Patients had a median (IQR) follow-up time of 71 (32-118) months. Median (IQR) age at time of diagnosis was 51 (41-61) years and 1292 (79.0%) were women. Overall, RD after initial treatment was seen in 25 patients (1.5%). The median (IQR) time to RD was 8.2 (3.6-16.5) months and 22 of the 25 (88%) patients developed RD within 2 years. Recurrent disease was not significantly different between both groups (group 1, n = 15 [1.3%]; group 2, n = 10 [2.1%]; difference, 0.8%; 95% CI, -0.5% to 2.5%). Of the 484 patients with nonincidental mPTC (group 2), 246 (50.8%) patients were treated with a hemithyroidectomy and follow-up in accordance with Dutch guidelines. Lymph node metastases were found in 1 of 246 (0.4%) patients after hemithyreoidectomy, and new mPTC in the contralateral thyroid was detected in 3 of 246 (1.2%) patients. Median (IQR) follow-up of this patient group was 37 (18-71) months. The 10-year probability of RD was 1.3% for patients without vascular invasion and 24.4% for patients with vascular invasion. Conclusions and Relevance: This nationwide cohort study found that overall, RD after hemithyroidectomy for patients with low-risk mPTC was rare (<2%). Based on these results, it seems reasonable to deescalate follow-up of patients with low-risk mPTC without vascular invasion after hemithyroidectomy. From a health care perspective, deescalation of follow-up may contribute to increased sustainability and accessibility to health care, both large challenges for the future.

A 15-year-old Girl with a Lateral Neck Mass Turning Out to Be Papillary Thyroid Carcinoma-Lateral Ectopic Papillary Thyroid Carcinoma or Lymph Node Metastasis?

Lateral neck lesions in children are common and involve various infectious or inflammatory etiologies as well as embryological remnants such as branchial cleft cysts. Although unusual, ectopic thyroid tissue can also present as a lateral neck mass. Here, we present an unusual case of a 15-year-old girl treated for an asymptomatic lateral neck mass that after surgical removal was found to be papillary thyroid carcinoma (PTC). However, after removal of the thyroid gland, no primary thyroid tumor was found. The question arose whether the lateral neck lesion was a lymph node metastasis without identifiable primary tumor (at histological evaluation) or rather malignant degeneration of ectopic thyroid tissue. Total thyroidectomy was performed with postoperative adjuvant radioactive iodine ablation. Even though PTC in a lateral neck mass without a primary thyroid tumor has been described previously, pediatric cases have not been reported. In this report we share our experience on diagnosis, treatment and follow-up, and review the existing literature.

Bilaterality, not multifocality, is an independent risk factor for recurrence in low-risk papillary thyroid cancer.

BACKGROUND: The impact of multifocality and bilaterality on recurrence in patients with low-risk papillary thyroid cancer (PTC) is relevant when considering patients for a de-escalated treatment strategy: hemithyroidectomy instead of total thyroidectomy followed with or without radioactive iodine. This study aims to analyze contralateral tumor probability in patients treated for low-risk PTC and assess multifocality and bilaterality as possible predictors for recurrence. METHODS: Patients with low-risk PTC treated with total thyroidectomy followed with or without radioactive iodine in the Netherlands between 2005 and 2015 were included in this study. Patients were identified from the Netherlands Comprehensive Cancer Organization (IKNL) and linked with the nationwide network and registry of Pathology in the Netherlands (PALGA). Contralateral tumor probability and recurrence were assessed. RESULTS: Of 791 included patients, 41.8% (331 of 791) had multifocal disease, with 68.9% (228 of 331) of those patients having bilateral disease. The contralateral tumor probability after hemithyroidectomy was 24.6% (150 of 610) for patients with unifocal disease and 43.1% (78 of 181) for patients with multifocal disease. We found a higher trend of recurrence in patients with bilateral disease, regardless of multifocality: in patients with contralateral disease after precompletion diagnosed unifocal disease 7.3% (11 of 150) had recurrent disease, and patients without contralateral disease after precompletion diagnosed multifocal disease 1.9% (2 per 103) had recurrence. Cox regression analysis showed that bilaterality (hazard ratio = 3.621, 95% confidence interval = 1.548 to 8.471) was the sole statistically significant risk factor for recurrence. CONCLUSION: Low recurrence rates are found in patients with either multifocal or bilateral disease with low-risk PTC. Bilaterality should be taken into account when considering these patients for de-escalated treatment strategy.