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.

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.

Clinical Prediction Models for Recurrence in Patients with Resectable Grade 1 and 2 Sporadic Non-Functional Pancreatic Neuroendocrine Tumors: A Systematic Review.

Recurrence after resection in patients with non-functional pancreatic neuroendocrine tumors (NF-pNET) has a considerable impact on overall survival. Accurate risk stratification will tailor optimal follow-up strategies. This systematic review assessed available prediction models, including their quality. This systematic review followed PRISMA and CHARMS guidelines. PubMed, Embase, and the Cochrane Library were searched up to December 2022 for studies that developed, updated, or validated prediction models for recurrence in resectable grade 1 or 2 NF-pNET. Studies were critically appraised. After screening 1883 studies, 14 studies with 3583 patients were included: 13 original prediction models and 1 prediction model validation. Four models were developed for preoperative and nine for postoperative use. Six models were presented as scoring systems, five as nomograms, and two as staging systems. The c statistic ranged from 0.67 to 0.94. The most frequently included predictors were tumor grade, tumor size, and lymph node positivity. Critical appraisal deemed all development studies as having a high risk of bias and the validation study as having a low risk of bias. This systematic review identified 13 prediction models for recurrence in resectable NF-pNET with external validations for 3 of them. External validation of prediction models improves their reliability and stimulates use in daily practice.

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.

Long-Term Oncological Outcomes of Papillary Thyroid Cancer and Follicular Thyroid Cancer in Children: A Nationwide Population-Based Study.

Introduction: Pediatric thyroid carcinoma is a rare malignancy and data on long-term oncological outcomes are sparse. The aim of this study was to describe the long-term oncological outcomes of pediatric papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) in a national cohort, and to identify risk factors for recurrence. Methods: We conducted a nationwide, retrospective cohort study, in which we combined two national databases. Patients aged <18 years, diagnosed with PTC or FTC in the Netherlands between 2000 and 2016, were included. pT-stage, pN-stage, multifocality and angioinvasion were included in a Cox-regression analysis for the identification of risk factors for recurrence. Results: 133 patients were included: 110 with PTC and 23 with FTC. Patients with PTC most often presented with pT2 tumors (24%) and pN1b (45%). During a median follow-up of 11.3 years, 21 patients with PTC developed a recurrence (19%). Nineteen recurrences were regional (91%) and 2 were pulmonary (9%). No risk factors for recurrence could be determined. One patient who developed pulmonary recurrence died two years later. Cause of death was not captured. Patients with FTC most often presented with pT2 tumors (57%). One patient presented with pN1b (4%). In 70%, no lymph nodes were collected. None of the patients with FTC developed a recurrence or died. Conclusion: Pediatric PTC and FTC are two distinct diseases. Recurrence in pediatric PTC is common, but in FTC it is not. Survival for both pediatric PTC and FTC is very good.

Treatment patterns for adrenal metastases using surgery and SABR during a 10-year period.

We studied treatment patterns for adrenal metastases using surgery or SABR at a single institution during a 10-year period. The number of patients undergoing SABR doubled since 2016, without a change in numbers undergoing surgery. Both treatments resulted in low rates of acute toxicity and similar survivals.

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.

International survey on opinions and use of minimally invasive surgery in small bowel neuroendocrine neoplasms.

INTRODUCTION: Although minimally invasive surgery is becoming the standard technique in gastrointestinal surgery, implementation for small bowel neuroendocrine neoplasms (SB-NEN) is lagging behind. The aim of this international survey was to gain insights into attitudes towards minimally invasive surgery for resection of SB-NEN and current practices. METHODS: An anonymous survey was sent to surgeons between February and May 2021 via (neuro)endocrine and colorectal societies worldwide. The survey consisted of questions regarding experience of the surgeon with minimally invasive SB-NEN resection and training. RESULTS: A total of 58 responses from five societies across 20 countries were included. Forty-one (71%) respondents worked at academic centers. Thirty-seven (64%) practiced colorectal surgery, 24 (41%) endocrine surgery and 45 (78%) had experience in advanced minimally invasive surgery. An open, laparoscopic or robotic approach was preferred by 23 (42%), 24 (44%), and 8 (15%) respondents, respectively. Reasons to opt for a minimally invasive approach were mainly related to peri-operative benefits, while an open approach was preferred for optimal mesenteric lymphadenectomy and tactile feedback. Additional training in minimally invasive SB-NEN resection was welcomed by 29 (52%) respondents. Forty-three (74%) respondents were interested in collaborating in future studies, with a cumulative median (IQR) annual case load of 172 (86-258). CONCLUSIONS: Among respondents, 69% applies minimally invasive surgery for resection of SB-NEN. Arguments for specific operative approaches differ, and insufficient training in advanced laparoscopic techniques seems to be a barrier. Future collaborative studies can provide better insight in selection criteria and optimal technique.

Synthesis and evaluation of [18F]cinacalcet for the imaging of parathyroid hyperplasia.

INTRODUCTION: Parathyroid hyperplasia is a disease characterized by overactive parathyroid glands secreting increased levels of parathyroid hormone. Surgical removal of the parathyroid glands is the standard treatment but requires precise pre-operative localization of the glands. However, currently available imaging modalities show limited sensitivity. Since positron emission tomography (PET) is a molecular imaging technique with high accuracy and sensitivity, our aim was to develop a new PET tracer for overactive parathyroid glands imaging by radiolabelling cinacalcet, a drug binding to the calcium-sensing receptor of the parathyroid glands. METHODS: [18F]Cinacalcet was synthesized by copper-catalysed [18F]trifluoromethylation of a boronic acid precursor using high molar activity [18F]fluoroform. Ex vivo biodistribution and metabolism were evaluated in 12 healthy male Wistar rats at 5, 15, 45 and 90 min. PET scans were performed at baseline and after blocking with NPS R-568. RESULTS: [18F]Cinacalcet was obtained in an overall radiosynthesis time of 1 h with a radiochemical purity of 98 ± 1%, a radiochemical yield of 8 ± 4% (overall, n = 7, corrected for decay) and a molar activity of 40 ± 11 GBq/µmol (n = 7, at EOS). The ex vivo biodistribution showed uptake in the thyroid and parathyroid glands as well as in other glands such as adrenals, salivary glands and pancreas. The tracer was rapidly cleared from the blood via liver and kidneys and showed fast metabolism. PET images confirmed uptake in the target organ. However, in a blocking study with NPS R-568 specific binding of [18F]cinacalcet to the CaSR could not be confirmed. CONCLUSIONS: [18F]Cinacalcet was successfully synthesized. First in vivo experiments in healthy rats showed uptake of the tracer in the target organ and fast metabolism, encouraging further in vivo evaluation of this tracer.

Complications After Thyroidectomy in Children: Lymph Node Dissection Is a Risk Factor for Permanent Hypocalcemia.

Background: Thyroidectomy is a treatment option in some benign thyroid disorders and the definitive treatment option for thyroid cancer. As postoperative mortality is extremely rare data on postoperative complications and long-term health consequences are important. Objective: To evaluate the frequencies of short- and long-term complications, and their risk factors in pediatric patients (0-18 years) who underwent a thyroidectomy in a tertiary children's hospital. Methods: A retrospective single center study was performed including all pediatric patients who underwent a thyroidectomy between January 2013 and February 2020. Results: Forty-eight patients were included in this study (mean age 14.6 years). Twenty-nine total thyroidectomies and 19 hemithyroidectomies were conducted. Thyroid carcinoma was the indication to perform a thyroidectomy in 12 patients, 36 patients underwent a thyroidectomy because of a benign thyroid disorder. Postoperative hypocalcemia was evaluated in patients who underwent a total thyroidectomy. Rapidly resolved hypocalcemia was observed in three patients (10.3%), transient hypocalcemia in 10 patients (34.5%) and permanent hypocalcemia in six patients (20.7%). Permanent hypocalcemia was only seen in patients who underwent a thyroidectomy combined with additional lymph node dissection because of thyroid carcinoma [thyroid carcinoma: OR 43.73, 95% CI (2.11-904.95); lymph node dissection: OR 76.14, 95% CI (3.49-458.98)]. Transient and permanent recurrent laryngeal nerve injury was reported in four (8.3%) and one (2.1%) of all patients, respectively. Conclusion: Permanent postoperative complications after thyroidectomy are rare in pediatric patients undergoing a thyroidectomy without lymph node dissection. However, in this age group permanent hypocalcemia occurs more frequently after thyroidectomy with additional lymph node dissection because of thyroid cancer. With respect to quality of life, especially of pediatric thyroid cancer patients, reducing this complication is an important goal.

Persistent Postthyroidectomy Hypoparathyroidism in the Netherlands.

Importance: Hypoparathyroidism is one of the most common complications after total or completion thyroidectomy. The reported incidence rate of hypoparathyroidism in the literature is highly variable. Data that provide a better understanding of the magnitude of this postoperative complication are warranted and can provide a stepping stone for further collaborations that aim to reduce complication rates and establish uniform treatment protocols. Objective: To evaluate the incidence of postoperative, persistent hypoparathyroidism after total or completion thyroidectomy in patients who were referred to university hospital centers and assess the association of different definitions with the incidence of hypoparathyroidism. Design, Setting, and Participants: This retrospective multicenter cohort study conducted throughout 2016 in 7 Dutch university hospital centers included 200 patients who were undergoing a total or completion thyroidectomy. Data analysis was conducted in January 2021. Main Outcomes and Measures: We report on the incidence of persistent hypoparathyroidism, defined as the need for active vitamin D with or without calcium supplementation longer than 1 year after surgery. Results: A total of 200 patients (143 women [71.5%]; mean [IQR] age, 49.0 [37.0-62.0] years) were included and 30 patients (15.0%) developed persistent hypoparathyroidism. The incidence of persistent hypoparathyroidism varied between 14.5% (calcium and active vitamin D 1 year postsurgery) to 28.5% (calcium and/or active vitamin D 6 months postsurgery) depending on the definition used. Conclusions and Relevance: In this cohort study, the risk of persistent hypoparathyroidism after total or completion thyroidectomy was 15% in patients who were referred to university hospital centers. The high rate of persistent hypoparathyroidism warrants efforts to reduce this complication rate. There is discrepancy in the definition and treatment of persistent hypoparathyroidism, and use of uniform evidence-based treatment guidelines enables comparison of interventions.

Postoperative morbidity and mortality after surgical resection of small bowel neuroendocrine neoplasms: A systematic review and meta-analysis.

Although small bowel resection is generally considered a low risk gastrointestinal procedure, this might not be true for small bowel neuroendocrine neoplasms (SB-NEN) as a result of potential central mesenteric involvement. We aimed to determine the reported morbidity and mortality after resection of SB-NEN in the literature and assess the effect of hospital volume on postoperative morbidity and mortality. A systematic review was performed by searching MEDLINE and Embase in March 2021. All studies reporting morbidity and/or mortality after SB-NEN resection were included. Pooled proportions of overall morbidity (Clavien-Dindo I-IV), severe morbidity (Clavien-Dindo III-IV), 30-day mortality, 90-day mortality and in-hospital mortality were calculated, as well as the association with hospital volume (high volume defined as the fourth quartile). Thirteen studies were included, with a total of 1087 patients. Pooled proportions revealed an overall morbidity of 13% (95% confidence interval [CI] = 7%-24%, I2  = 90%), severe morbidity of 7% (95% CI = 4%-14%, I2  = 70%), 30-day mortality of 2% (95% CI = 1%-3%, I2  = 0%), 90-day mortality of2% (95% CI = 2%-4%, I2  = 35%) and in-hospital mortality of 1% (95% CI = 0%-2%, I2  = 0%). An annual hospital volume of nine or more resections was associated with lower overall and severe morbidity compared to lower volume: 10% vs 15% and 4% vs 9%, respectively. Thirty-day mortality was similar (2% vs 1%) and 90-day mortality was higher in high-volume hospitals: 4% vs 1%. This systematic review with meta-analyses showed severe morbidity of 7% and low mortality rates after resection of SB-NEN. The currently available literature suggests a certain impact of hospital volume on postoperative outcomes, although heterogeneity among the included studies constrains interpretation.

Parathyroid Function Saving Total Thyroidectomy Using Autofluorescence and Quantified Indocyanine Green Angiography.

Introduction: Postoperative hypoparathyroidism is one of the most common complications after total thyroidectomy. In recent years, several techniques have been employed, trying to save parathyroid glands during thyroid surgery, such as autofluorescence and indocyanine green (ICG) angiography. In this study, we present a systematic approach to a parathyroid function saving total thyroidectomy using autofluorescence and quantified ICG angiography. Materials and Methods: Step-by-step video demonstration of a total thyroidectomy for thyroid cancer utilizing parathyroid autofluorescence and ICG angiography. Results: A systematic step-wise approach to a total thyroidectomy using autofluorescence and quantified ICG angiography is demonstrated. The set moments of deployment, settings of the camera, and a standardized workflow model for parathyroid autofluorescence and ICG angiography are noted. Conclusion: A systematic approach to parathyroid autofluorescence and quantified ICG angiography during total thyroidectomy may eventually guide the surgeon in early identification of the parathyroid glands and the need for parathyroid autotransplantation, thereby predicting and preventing postoperative hypoparathyroidism. The authors have no related personal conflicts of interest to declare that could be perceived as prejudicing the impartiality of the research reported. For this study, the Quest Spectrum was used. The authors have no conflicts with this or any other commercial entity. This research did not receive any specific grant from any funding agency in the public or commercial sector. Runtime of video: 9 mins 59 secs This video was presented at the Third Symposium on Parathyroid Fluorescence 2021.

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.

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.

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.

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.