Bariatric-metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): a multicentre, open-label, randomised trial.

BACKGROUND: Observational studies suggest that bariatric-metabolic surgery might greatly improve non-alcoholic steatohepatitis (NASH). However, the efficacy of surgery on NASH has not yet been compared with the effects of lifestyle interventions and medical therapy in a randomised trial. METHODS: We did a multicentre, open-label, randomised trial at three major hospitals in Rome, Italy. We included participants aged 25-70 years with obesity (BMI 30-55 kg/m2), with or without type 2 diabetes, with histologically confirmed NASH. We randomly assigned (1:1:1) participants to lifestyle modification plus best medical care, Roux-en-Y gastric bypass, or sleeve gastrectomy. The primary endpoint of the study was histological resolution of NASH without worsening of fibrosis at 1-year follow-up. This study is registered at ClinicalTrials.gov, NCT03524365. FINDINGS: Between April 15, 2019, and June 21, 2021, we biopsy screened 431 participants; of these, 103 (24%) did not have histological NASH and 40 (9%) declined to participate. We randomly assigned 288 (67%) participants with biopsy-proven NASH to lifestyle modification plus best medical care (n=96 [33%]), Roux-en-Y gastric bypass (n=96 [33%]), or sleeve gastrectomy (n=96 [33%]). In the intention-to-treat analysis, the percentage of participants who met the primary endpoint was significantly higher in the Roux-en-Y gastric bypass group (54 [56%]) and sleeve gastrectomy group (55 [57%]) compared with lifestyle modification (15 [16%]; p<0·0001). The calculated probability of NASH resolution was 3·60 times greater (95% CI 2·19-5·92; p<0·0001) in the Roux-en-Y gastric bypass group and 3·67 times greater (2·23-6·02; p<0·0001) in the sleeve gastrectomy group compared with in the lifestyle modification group. In the per protocol analysis (236 [82%] participants who completed the trial), the primary endpoint was met in 54 (70%) of 77 participants in the Roux-en-Y gastric bypass group and 55 (70%) of 79 participants in the sleeve gastrectomy group, compared with 15 (19%) of 80 in the lifestyle modification group (p<0·0001). No deaths or life-threatening complications were reported in this study. Severe adverse events occurred in ten (6%) participants who had bariatric-metabolic surgery, but these participants did not require re-operations and severe adverse events were resolved with medical or endoscopic management. INTERPRETATION: Bariatric-metabolic surgery is more effective than lifestyle interventions and optimised medical therapy in the treatment of NASH. FUNDING: Fondazione Policlinico Universitario A Gemelli, Policlinico Universitario Umberto I and S Camillo Hospital, Rome, Italy.

Single Institution Experience in the Management of Locally Advanced (pT4) Differentiated Thyroid Carcinomas.

BACKGROUND: Locally infiltrating (T4) differentiated thyroid carcinomas (DTC) represent a challenge. Surgical strategy and adjuvant therapy should be planned balancing morbidity and oncologic outcome. A series of patients with T4 DTC who underwent multidisciplinary evaluation and treatment is reported. The main study endpoints were the oncologic outcome, complication rates, and risk factors for tumor recurrence. PATIENTS AND METHODS: All DTC cases operated between 2009 and 2021 were reviewed and T4 DTC cases were identified. En bloc resection of inferior laryngeal nerve (ILN), tracheal, and/or internal jugular vein (IJV) was performed in cases of massive infiltration. In cases of pharyngoesophageal junction (PEJ) invasion, the shaving technique was always applied. RESULTS: Among 4775 DTC cases, 60 were T4. ILN infiltration was documented in 45 cases (en bloc resection in 9), tracheal infiltration in 14 (tracheal resection in 2), PEJ invasion in 11 (R0 resection in 7 cases and < 1 cm residual tissue in 4 cases), IJV resection in 6, and laryngeal in 2. In total, 11 postoperative ILN palsy, 23 transient hypoparathyroidisms, and 2 hematomas requiring reoperation were registered. Final histology showed 7 pN0, 22 pN1a, and 31 pN1b tumors. Aggressive variants were observed in 47 patients. All but 1 patient underwent radioiodine treatment, 12 underwent adjuvant external beam radiation therapy (EBRT), and 2 underwent chemotherapy. At a median follow-up of 58 months, no tumor-related death was registered, and seven patients required reoperation for recurrence. Tracheal invasion was the only significant factor negatively impacting recurrence (p = 0.045). CONCLUSIONS: A multidisciplinary approach is essential for the management of T4 DTC. Individualized and balanced surgical strategy and adjuvant treatments, in particular EBRT, ensure control of locally advanced disease with acceptable morbidity.

One-Anastomosis Gastric Bypass (OABG) vs. Single Anastomosis Duodeno-Ileal Bypass (SADI) as revisional procedure following Sleeve Gastrectomy: results of a multicenter study.

PURPOSE: Sleeve Gastrectomy (SG) is the most performed bariatric surgery, but a considerable number of patients may require revisional procedures for suboptimal clinical response/recurrence of weight (SCR/RoW). Conversion options include One-Anastomosis Gastric Bypass (OAGB) and Single Anastomosis Duodeno-Ileal Bypass (SADI). The study aims to compare SADI vs. OAGB as revisional procedures in terms of early and mid-term complications, operative time, postoperative hospital stay and clinical outcomes. METHODS: All patients who underwent OAGB or SADI as revisional procedures following SG for SCR/RoW at three high-volume bariatric centers between January 2014 and April 2021 were included. Propensity score matching (PSM) analysis was performed. Demographic, operative, and postoperative outcomes of the two groups were compared. RESULTS: One hundred and sixty-eight patients were identified. After PSM, the two groups included 42 OAGB and 42 SADI patients. Early (≤ 30 days) postoperative complications rate did not differ significantly between OAGB and SADI groups (3 bleedings vs. 0, p = 0.241). Mid-term (within 2 years) complications rate was significantly higher in the OAGB group (21.4% vs. 2.4%, p = 0.007), mainly anastomotic complications and reflux disease (12% of OAGBs). Seven OAGB patients required conversion to another procedure (Roux-en-Y Gastric Bypass-RYGB) vs. none among the SADI patients (p = 0.006). CONCLUSIONS: SADI and OAGB are both effective as revisional procedures for SCR/RoW after SG. OAGB is associated with a significantly higher rate of mid-term complications and a not negligible rate of conversion (RYGB). Larger studies are necessary to draw definitive conclusions.

Accurate liquid biopsy for the diagnosis of non-alcoholic steatohepatitis and liver fibrosis.

OBJECTIVE: Clinical diagnosis and approval of new medications for non-alcoholic steatohepatitis (NASH) require invasive liver biopsies. The aim of our study was to identify non-invasive biomarkers of NASH and/or liver fibrosis. DESIGN: This multicentre study includes 250 patients (discovery cohort, n=100 subjects (Bariatric Surgery Versus Non-alcoholic Steato-hepatitis - BRAVES trial); validation cohort, n=150 (Liquid Biopsy for NASH and Liver Fibrosis - LIBRA trial)) with histologically proven non-alcoholic fatty liver (NAFL) or NASH with or without fibrosis. Proteomics was performed in monocytes and hepatic stellate cells (HSCs) with iTRAQ-nano- Liquid Chromatography - Mass Spectrometry/Mass Spectrometry (LC-MS/MS), while flow cytometry measured perilipin-2 (PLIN2) and RAB14 in peripheral blood CD14+CD16- monocytes. Neural network classifiers were used to predict presence/absence of NASH and NASH stages. Logistic bootstrap-based regression was used to measure the accuracy of predicting liver fibrosis. RESULTS: The algorithm for NASH using PLIN2 mean florescence intensity (MFI) combined with waist circumference, triglyceride, alanine aminotransferase (ALT) and presence/absence of diabetes as covariates had an accuracy of 93% in the discovery cohort and of 92% in the validation cohort. Sensitivity and specificity were 95% and 90% in the discovery cohort and 88% and 100% in the validation cohort, respectively.The area under the receiver operating characteristic (AUROC) for NAS level prediction ranged from 83.7% (CI 75.6% to 91.8%) in the discovery cohort to 97.8% (CI 95.8% to 99.8%) in the validation cohort.The algorithm including RAB14 MFI, age, waist circumference, high-density lipoprotein cholesterol, plasma glucose and ALT levels as covariates to predict the presence of liver fibrosis yielded an AUROC of 95.9% (CI 87.9% to 100%) in the discovery cohort and 99.3% (CI 98.1% to 100%) in the validation cohort, respectively. Accuracy was 99.25%, sensitivity 100% and specificity 95.8% in the discovery cohort and 97.6%, 99% and 89.6% in the validation cohort. This novel biomarker was superior to currently used FIB4, non-alcoholic fatty liver disease fibrosis score and aspartate aminotransferase (AST)-to-platelet ratio and was comparable to ultrasound two-dimensional shear wave elastography. CONCLUSIONS: The proposed novel liquid biopsy is accurate, sensitive and specific in diagnosing the presence and severity of NASH or liver fibrosis and is more reliable than currently used biomarkers. CLINICAL TRIALS: Discovery multicentre cohort: Bariatric Surgery versus Non-Alcoholic Steatohepatitis, BRAVES, ClinicalTrials.gov identifier: NCT03524365.Validation multicentre cohort: Liquid Biopsy for NASH and Fibrosis, LIBRA, ClinicalTrials.gov identifier: NCT04677101.

Is There Any Reliable Predictor of Functional Recovery Following Post-thyroidectomy Vocal Fold Paralysis?

BACKGROUND: Predicting definitive outcomes of post-thyroidectomy vocal fold paralysis (VFP) is challenging. We aimed to identify reliable predictors based on intraoperative neuromonitoring (IONM) and flexible fiberoptic laryngostroboscopy (FFL) findings. METHODS: Among 1172 thyroid operations performed from April to December 2021, all patients who exhibited vocal fold paralysis (VFP) at post-operative laryngoscopy were included. IONM data, including type of loss of signal (LOS), were collected. Patients underwent FFL, with arytenoid motility assessment, at 15, 45 and 120 days post-operatively. Patients were divided into two groups: those who recovered vocal fold motility (VFM) by the 120th post-operative day (recovery group) and those who did not (non-recovery group). RESULTS: Fifty-nine VFP cases (5.0% of total patients) met the inclusion criteria. Eight patients were lost at follow-up and were excluded. Overall, 9 patients were included in the non-recovery group (0.8% of total patients) and 42 in the recovery group. Among various predictive factors, only arytenoid fixation (AF) at the 15th post-operative day and Type I LOS were significant predictors for no VFM recovery (p = 0.007, RR = 9.739, CI:1.3-72.3 and p = 0.001, RR = 9.25, CI:2.2-39.3 for AF and Type I injury, respectively). The combination of type of LOS and arytenoid motility at the 15th post-op day yielded satisfactory predictive values for the progression of transient VFP to permanent. CONCLUSIONS: Arytenoid motility at the 15th post-op day and type II LOS are associated with recovery of VFM. Type of LOS and FFL could be included in the follow-up protocols of patients with VFP to reliably predict clinical outcomes.

SICOB-endorsed national Delphi consensus on obesity treatment optimization: focus on diagnosis, pre-operative management, and weight regain/insufficient weight loss approach.

PURPOSE: Overweight and obesity affects 60% of adults causing more than 1.2 million deaths across world every year. Fight against involved different specialist figures and multiple are the approved weapons. Aim of the present survey endorsed by the Italian Society of Bariatric Surgery (SICOB) is to reach a national consensus on obesity treatment optimization through a Delphi process. METHODS: Eleven key opinion leaders (KOLs) identified 22 statements with a major need of clarification and debate. The explored pathways were: (1) Management of patient candidate to bariatric/metabolic surgery (BMS); (2) Management of patient not eligible for BMS; (3) Management of patient with short-term (2 years) weight regain (WR) or insufficient weight loss (IWL); (4) Management of the patient with medium-term (5 years) WR; and (5) Association between drugs and BMS as WR prevention. The questionnaire was distributed to 65 national experts via an online platform with anonymized results. RESULTS: 54 out of 65 invited panelists (83%) respond. Positive consensus was reached for 18/22 statements (82%); while, negative consensus (s20.4; s21.5) and no consensus (s11.5, s17) were reached for 2 statements, respectively (9%). CONCLUSION: The Delphi results underline the importance of first-line interdisciplinary management, with large pre-treatment examination, and establish a common opinion on how to properly manage post-operative IWL/WR. LEVEL OF EVIDENCE V: Report of expert committees.

Approach to FNA of Thyroid Gland Cysts.

Fine needle aspiration is a well-known procedure for the diagnosis and management of thyroid lesions, representing the first diagnostic tool for the definition of their nature. In clinical practice, a thyroid nodule can be classified as solid, cystic, and partially cystic based on its internal components. Different thyroid imaging reporting systems and cytologic diagnostic systems have focused their attention on solid nodules, which are more frequently linked with a malignant outcome. In fact, numerous papers demonstrated that nodules with microcalcifications, a taller-than-wide shape, hypoechogeneity, and irregular margins, are more likely to be malignant on histology. Nevertheless, according to the literature, the risk of malignancy in a partially cystic thyroid nodule ranges between 3.3 and 17-5%, including, for instance, the possible diagnosis of a cystic papillary thyroid carcinoma and other malignant entities. Therefore, in the current review article, we are going to discuss the approach to thyroid cystic lesions on fine needle aspiration cytology.

Integration of molecular imaging in the personalized approach of patients with adrenal masses.

Adrenal masses are a frequent finding in clinical practice. Many of them are incidentally discovered with a prevalence of 4% in patients undergoing abdominal anatomic imaging and require a differential diagnosis. Biochemical tests, evaluating hormonal production of both adrenal cortex and medulla (in particular, mineralocorticoids, glucocorticoids and catecholamines), have a primary importance in distinguishing functional or non-functional lesions. Conventional imaging techniques, in particular computerized tomography (CT) and magnetic resonance imaging (MRI), are required to differentiate between benign and malignant lesions according to their appearance (size stability, contrast enhanced CT and/or chemical shift on MRI). In selected patients, functional imaging is a non-invasive tool able to explore the metabolic pathways involved thus providing additional diagnostic information. Several single photon emission tomography (SPET) and positron emission tomography (PET) radiopharmaceuticals have been developed and are available, each of them suitable for studying specific pathological conditions. In functional masses causing hypersecreting diseases (mainly adrenal hypercortisolism, primary hyperaldosteronism and pheochromocytoma), functional imaging can lateralize the involvement and guide the therapeutic strategy in both unilateral and bilateral lesions. In non-functioning adrenal masses with inconclusive imaging findings at CT/MR, [18F]-FDG evaluation of tumor metabolism can be helpful to characterize them by distinguishing between benign nodules and primary malignant adrenal disease (mainly adrenocortical carcinoma), thus modulating the surgical approach. In oncologic patients, [18F]-FDG uptake can differentiate between benign nodule and adrenal metastasis from extra-adrenal primary malignancies.

Robot-assisted vs laparoscopic lateral transabdominal adrenalectomy: a propensity score matching analysis.

BACKGROUND: Laparoscopic adrenalectomy (LA) is the gold standard treatment for adrenal lesions. Robot-assisted adrenalectomy (RAA) is a safe approach, associated with higher costs in absence of clear-cut benefits. Several series reported some advantages of RAA over LA in challenging cases, but definitive conclusions are lacking. We evaluated the cost effectiveness and outcomes of robotic (R-LTA) and laparoscopic (L-LTA) approach for lateral transabdominal adrenalectomy in a high-volume center. METHODS: Among 356 minimally invasive adrenalectomies (January 2012-August 2021), 286 were performed with a lateral transabdominal approach: 191 L-LTA and 95 R-LTA. The R-LTA and L-LTA patients were matched for lesion side and size, hormone secretion, and BMI with propensity score matching (PSM) analysis. Postoperative complications, operative time (OT), postoperative stay (POS), and costs were compared. RESULTS: PSM analysis identified 184 patients, 92 in R-LTA and 92 in L-LTA group. The two groups were well matched. The median lesion size was 4 cm in both groups (p = 0.533). Hormonal hypersecretion was detected in 55 and 54 patients of R-LTA and L-LTA group, respectively (p = 1). Median OT was significantly longer in R-LTA group (90.0 vs 65.0 min) (p < 0.001). No conversion was registered. Median POS was similar (4.0 vs 3.0 days in the R-LTA and L-LTA) (p = 0.467). No difference in postoperative complications was found (p = 1). The cost margin analysis showed a positive income for both procedures (3137 vs 3968 € for R-LTA and L-LTA). In the multiple logistic regression analysis, independent risk factors for postoperative complications were hypercortisolism (OR = 3.926, p = 0.049) and OT > 75 min (OR = 8.177, p = 0.048). CONCLUSIONS: The postoperative outcomes of R-LTA and L-TLA were similar in our experience. Despite the higher cost, RAA appears to be cost effective and economically sustainable in a high-volume center (60 adrenalectomies/year), especially if performed in challenging cases, including patients with large (> 6 cm) and/or functioning tumors.

Single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S): experience from a high-bariatric volume center.

PURPOSE: Biliopancreatic diversion with duodenal switch and single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) are technically demanding hypo-absorptive bariatric procedures generally indicated in super-obese patients (BMI ≥ 50 kg/m2). Data from the literature prove the procedure to be safe and effective, with promising bariatric and metabolic effects. Anyway, international societies support the creation of multicentric national and international registries to obtain more homogeneous data over the long period. We aimed to report our experience with this procedure. METHODS: Among 2313 patients who underwent bariatric procedures at our institution, between July 2016 and August 2021, 121 (5.2%) consenting patients were scheduled for SADI-S as primary (SADIS) or revisional procedure after sleeve gastrectomy (SADI) (respectively 87 and 34 patients). Early and late post-operative complications, operative time, post-operative stay, and follow-up data were analyzed. RESULTS: Overall, the median preoperative BMI was 52.3 (48.75-57.05) kg/m2 with a median age of 44 (39-51) years, the median operative time was 120 (100-155) min. Complications at 30th-day post-op were registered in 4 (3.3%) patients and late complications in 4 (3.3%) patients. At a median follow-up of 31 (14-39) months, the median percentage excess weight loss was 79.8 (55.15-91.45)%, and the median total weight loss was 57.0650 (43.3925-71.3475)%. CONCLUSION: Our data, coherently with the literature, confirm that SADI-S is a safe, effective procedure with acceptable complications rate. Larger studies with longer follow-ups are necessary to draw definitive conclusions.

Small intestinal metabolism is central to whole-body insulin resistance.

OBJECTIVE: To assess the role of jejunum in insulin resistance in humans and in experimental animals. DESIGN: Twenty-four subjects undergoing biliopancreatic diversion (BPD) or Roux-en-Y gastric bypass (RYGB) were enrolled. Insulin sensitivity was measured at baseline and at 1 week after surgery using oral glucose minimal model.We excluded the jejunum from intestinal continuity in pigs and created a jejunal loop with its vascular and nerve supply intact accessible from two cutaneous stomas, and reconnected the bowel with an end-to-end anastomosis. Glucose stable isotopes were given in the stomach or in the jejunal loop.In vitro studies using primary porcine and human hepatocytes or myoblasts tested the effects of plasma on gluconeogenesis or glucose uptake and insulin signalling. RESULTS: Whole-body insulin sensitivity (SI∙104: 0.54±0.12 before vs 0.82±0.11 after BPD, p=0.024 and 0.41±0.09 before vs 0.65±0.09/pM/min after RYGB, p=not significant) and Glucose Disposition Index increased only after BPD. In pigs, insulin sensitivity was significantly lower when glucose was administered in the jejunal loop than in the stomach (glucose rate of disappearance (Rd) area under the curve (AUC)/insulin AUC∙10: 1.82±0.31 vs 2.96±0.33 mmol/pM/min, p=0.0017).Metabolomics showed a similar pattern before surgery and during jejunal-loop stimulation, pointing to a higher expression of gluconeogenetic substrates, a metabolic signature of impaired insulin sensitivity.A greater hepatocyte phosphoenolpyruvate-carboxykinase and glucose-6-phosphatase gene expression was elicited with plasma from porcine jejunal loop or before surgery compared with plasma from jejunectomy in pigs or jejunal bypass in humans.Stimulation of myoblasts with plasma from porcine jejunal loop or before surgery reduced glucose uptake, Ser473-Akt phosphorylation and GLUT4 expression compared with plasma obtained during gastric glucose administration after jejunectomy in pigs or after jejunal bypass in humans. CONCLUSION: Proximal gut plays a crucial role in controlling insulin sensitivity through a distinctive metabolic signature involving hepatic gluconeogenesis and muscle insulin resistance. Bypassing the jejunum is beneficial in terms of insulin-mediated glucose disposal in obesity. TRIAL REGISTRATION NUMBER: NCT03111953.

Analysis and outcomes of wrong site thyroid surgery.

BACKGROUND: In thyroid surgery, wrong-site surgery (WSS) is considered a rare event and seldom reported in the literature. CASE PRESENTATION: This report presents 5 WSS cases following thyroid surgery in a 20-year period. We stratified the subtypes of WSS in wrong target, wrong side, wrong procedure and wrong patient. Only planned and elective thyroid surgeries present WSS cases. The interventions were performed in low-volume hospitals, and subsequently, the patients were referred to our centres. Four cases of wrong-target procedures (thymectomies [n = 3] and lymph node excision [n = 1] performed instead of thyroidectomies) and one case of wrong-side procedure were observed in this study. Two wrong target cases resulting additionally in wrong procedure were noted. Wrong patient cases were not detected in the review. Patients experienced benign, malignant, or suspicious pathology and underwent traditional surgery (no endoscopic or robotic surgery). 40% of WSS led to legal action against the surgeon or a monetary settlement. CONCLUSION: WSS is also observed in thyroid surgery. Considering that reports regarding the serious complications of WSS are not yet available, these complications should be discussed with the surgical community. Etiologic causes, outcomes, preventive strategies of WSS and expert opinion are presented.

Preoperative psychological characteristics affecting mid-term outcome after bariatric surgery: a follow-up study.

BACKGROUND: The purpose of this study was to investigate the relationship between preoperative psychological factors and percentage of total weight loss (%TWL) after laparoscopic Roux-en-Y gastric bypass (LRYGB) to identify possible psychological therapy targets to improve the outcome of bariatric surgery. METHODS: Seventy-six patients completed the Hamilton's Anxiety and Depression Scales (HAM-A, HAM-D) and Toronto Alexithymia Scale (TAS-20) the day before surgery (T0). The pre-operative body weight and the %TWL at 3 (T1), 6 (T2), and 24-30 (T3) months were collected. RESULTS: At T3, depressed and alexithymic patients showed a lower %TWL compared to non-depressed patients (p = 0.03) and to non-alexithymic patients (p = 0.02), respectively. Finally, patients who had at least one of the three analyzed psychological factors showed less weight loss, at T2 (p = 0.02) and T3 (p = 0.0004). CONCLUSIONS: Psychological factors may also affect long-term outcome of bariatric surgery. This study shows an association between alexithymia/depression pre-operative levels and the weight loss at 30 months'follow-up after bariatric surgery. LEVEL OF EVIDENCE: Level III, longitudinal cohort study.

SPONTANEOUS THYROID NODULE HEMORRHAGE IN THE EMERGENCY DEPARTMENT.

Objective: Spontaneous thyroid gland hemorrhage is a rare event. The present retrospective study considered its clinical impact and management in a referral center. Methods: Clinical records of adult patients accessed in the last 10 years (2009-2018) in the Emergency Department of Policlinico Gemelli IRCCS were reviewed to study patients with spontaneous thyroid nodule hemorrhage. All demographic and radiologic or surgical parameters were included, with special attention to the characteristics of thyroid disease and clinical management. Results: Among the 631,129 adults who were registered during the period considered, 59 consecutive patients were included in the study. The mean age was 48.3 ± 14.3 years, with a prevalence of females. The main symptoms were acute neck pain, dyspnea, and dysphagia. All patients underwent ultrasound evaluation; computed tomography scan was performed on only 3 patients, finding one case of active intranodular bleeding requiring urgent surgery. Six patients required hospitalization; the others were discharged and referred for ambulatory endocrinology follow-up. Among them, 7 patients underwent surgery in the next 6 months, with malignant disease found in 3 cases (5.1%). Conclusion: Intrathyroidal spontaneous hemorrhage is a rare event, occurring in multinodular as well as in single-nodule thyroid disease. Although the clinical course is mostly benign, this condition should be carefully evaluated as, in rare circumstances, active bleeding could induce airway obstruction with the need for emergency surgery. Patients should be referred to endocrinology ambulatory follow-up because bleeding could arise as the first sign of malignant lesions in some cases. Abbreviations: CT = computed tomography; ED = emergency department; FNA = fine-needle aspiration; US = ultrasound.

Relevance of rosette patterns in variants of papillary thyroid carcinoma.

INTRODUCTION: The detection of rosette-like clusters (RLC) of follicular cells in thyroid carcinoma has been reported mostly in the columnar cell variant of papillary thyroid carcinoma (PTC). Despite the fact that diagnosing variants of PTC is no longer encouraged by The Bethesda System for Reporting Thyroid Cytopathology, the identification of cytomorphological features such as RLC linked with these tumours might help reduce possible misinterpretation in thyroid fine needle aspiration (FNA) cytology. We accordingly investigated the potential correlation of architectural patterns including RLC with PTC variants. METHODS: We analysed 225 thyroid FNA cytology cases diagnosed as suspicious for malignancy (SFM) and positive for malignancy (M) over a 1-year time where all samples had corresponding histology. We also included 150 benign lesions from the same period. The presence of RLC vs similar appearing solid clusters, papillary structures and microfollicles were evaluated. We also performed immunocytochemistry and molecular testing for BRAFV600E. RESULTS: We included 100 (44.4%) SFM favouring PTC and 125 (55.6%) M cases with cyto-histological correlation. On histology, all SFM and M cases showed malignancy including 140 (62.2%) classic PTC and 85 (37.8%) PTC variants. The cytomorphological patterns in all FNA samples included solid (74%), papillary (89%), microfollicular (70%), and pseudo-RLC morphology (25.7%). We identified only pseudo-RLC in 33 FNA specimens from PTC variant cases that included tall cell variant (42.4%), hobnail variant (21.2%) and miscellaneous variants (36.3%) of PTC. No definitive RLC were detected in our series. Immunocytochemistry and BRAFV600E were not specifically linked with an RLC pattern. CONCLUSIONS: These findings demonstrate that in our dataset the architectural pattern of RLC was not recognised within PTC variants. However, we did identify a pseudo-RLC pattern that was observed in association with tall cell variant and hobnail variant cases of PTC.

Development of an ontology for laparoscopic transabdominal adrenalectomy via a comprehensive modified Delphi survey and its validation on a multicentric pilot data set for surgical training and future video analysis with machine learning algorithms.

Surgical technique is essential to ensure safe minimally invasive adrenalectomy. Due to the relative rarity of adrenal surgery, it is challenging to ensure adequate exposure in surgical training. Surgical video analysis supports auto-evaluation, expert assessment and could be a target for automatization. The developed ontology was validated by a European expert consensus and is applicable across the surgical techniques encountered in all participating centres, with an exemplary demonstration in bi-centric recordings. Standardization of adrenalectomy video analysis may foster surgical training and enable machine learning training for automated safety alerts.

Conversion During Laparoscopic Adrenalectomy for Pheochromocytoma: A Cohort Study in 244 Patients.

BACKGROUND: Recent advances in anesthetic and laparoscopic surgical management have improved perioperative outcomes in patients with pheochromocytoma. However, patients converted to laparotomy during laparoscopic adrenalectomy for pheochromocytoma have never been evaluated specifically in terms of intraoperative hemodynamic instability and postoperative complications. METHODS: Retrospective analysis of prospectively maintained databases in five medical centers from 2002 to 2013. Inclusion criteria were consecutive patients who underwent laparoscopic unilateral total adrenalectomy for pheochromocytoma. RESULTS: Two hundred forty-four patients were included. Mean tumor size was 43.9 ± 20 mm with 92 patients (38%) having a tumor diameter > 50 mm. During adrenalectomy, 19 of 244 patients (7.7%) had to be converted to laparotomy. In multivariable analysis, the need for preoperative hospitalization (3.379, 1.209-9.445; P = 0.020), tumor size > 6 cm (2.97, 0.996-8.868; P = 0.050), and ratio of intraoperative systolic blood pressure >200 mmHg duration to anesthesia duration (1.060, 1.007-1.117; P = 0.027) remained significantly associated with conversion. Conversion was significantly associated with postoperative grade II-V Clavien morbidity rate (4.259, 1.471-12.326; P = 0.007) and duration of hospitalization (12.92, 2.90-58.82; P < 0.001). CONCLUSIONS: This study shows that preoperative hospitalization and larger tumor were more frequent in patients undergoing conversion to laparotomy during laparoscopic adrenalectomy for pheochromocytoma. Conversion is associated with increased intraoperative hypertensive episodes and postoperative complications rate. Clinicians should be cognizant of these risks and prepare patients appropriately for conversion when deemed necessary.

Training in endocrine surgery.

BACKGROUND/PURPOSE: In Europe, the Division of Endocrine Surgery (DES) determines the number of operations (thyroid, neck dissection, parathyroids, adrenals, neuroendocrine tumors of the gastro-entero-pancreatic tract (GEP-NETs)) to be required for the European Board of Surgery Qualification in (neck) endocrine surgery. However, it is the national surgical boards that determine how surgical training is delivered in their respective countries. There is a lack of knowledge on the current situation concerning the training of surgical residents and fellows with regard to (neck) endocrine surgery in Europe. METHODS: A survey was sent out to all 28 current national delegates of the DES. One questionnaire was addressing the training of surgical residents while the other was addressing the training of fellows in endocrine surgery. Particular focus was put on the numbers of operations considered appropriate. RESULTS: For most of the operations, the overall number as defined by national surgical boards matched quite well the views of the national delegates even though differences exist between countries. In addition, the current numbers required for the EBSQ exam are well within this range for thyroid and parathyroid procedures but below for neck dissections as well as operations on the adrenals and GEP-NETs. CONCLUSIONS: Training in endocrine surgery should be performed in units that perform a minimum of 100 thyroid, 50 parathyroid, 15 adrenal, and/or 10 GEP-NET operations yearly. Fellows should be expected to have been the performing surgeon of a minimum of 50 thyroid operations, 10 (central or lateral) lymph node dissections, 15 parathyroid, 5 adrenal, and 5 GEP-NET operations.