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.

Differentiating Benign from Malignant Adrenocortical Tumors by a Single Morphological Parameter-a Clinicopathological Study on 837 Adrenocortical Neoplasias.

The morphological differentiation between benign and malignant adrenocortical tumors is an ongoing problem in diagnostic pathology. In recent decades the complex scoring systems have been widely used to calculate the probability of malignancy in adrenocortical tumors on the basis of a variety of histomorphological parameters. We herewith present a substantially simplified method to diagnose adrenocortical carcinoma by a single histomorphological parameter on a consecutive series of more than 800 adrenocortical tumors. Between January 2000 and May 2019, altogether 2305 adrenalectomies for of all types of diseases were removed, approximately 98% by minimally invasive approaches. After exclusion of pheochromocytomas, adrenal ganglioneuromas, adrenal metastases, Cushing's disease related specimens, and Conn's adenomas, the present series finally consisted of 837 adrenocortical tumors. All tumors were analyzed by experienced pathologists of a single institution using standard histopathological methods (Hematoxylin-Eosin and Ki67 stained sections). Clinical and histopathologic data were prospectively collected and retrospectively analyzed. Clinically, 385 patients had 420 functioning tumors (FT), and 417 had non-functioning adrenal tumors (NFT). The mean size of FT was 3.8 ± 1.4 cm (range 0.5-16 cm) and for NFT 4.5 ± 1.6 cm (range 1.5-18 cm). Histomorphologically, 32 adrenal tumors were classified as adrenocortical carcinoma (ACC; 3.8%). In all 32 cases (tumor size 9.1 ± 4.0 cm, range 3-18 cm), confluenting tumor necrosis could be demonstrated. The remaining 805 tumors (control group) completely lacked this highly reproducible single morphological feature. Ki67 levels above 10% were found in 31 of 32 ACCs and never in adrenocortical adenomas (ACA). With a mean follow-up of 8.2 years, 24 out of 32 patients primarily diagnosed as ACC developed distant metastases (75.0%), whereas all patients in the control group remained free of local or distant recurrence. We conclude that a single morphological parameter (confluenting tumor necrosis) is sufficient to predict a poor clinical course in adrenocortical tumors. The histomorphological diagnosis of this parameter is straightforward and highly reproducible.

Fluorescence-enabled assessment of adrenal gland localization and perfusion in posterior retroperitoneoscopic adrenal surgery in a preclinical model.

BACKGROUND: The posterior retroperitoneoscopic adrenal access represents a challenge in orientation and working space creation. The aim of this experimental acute study was to evaluate the impact of computer-assisted quantitative fluorescence imaging on adrenal gland identification and assessment of intraoperative remnant perfusion for adrenal resection in the posterior retroperitoneoscopic approach. METHODS: Six pigs underwent simultaneous (n = 5) or sequential (n = 1) bilateral posterior retroperitoneoscopic adrenalectomy (n = 12). Fluorescence imaging was obtained via intravenous administration of 3 mL of Indocyanine Green (ICG) and by switching the camera systems to near-infrared mode (D-LIGHT P, KARL STORZ; Germany). Fluorescence-based visualization of adrenal glands before vascular division (n = 4), after the main vascular pedicle ligation (negative control, n = 1) or after adrenal resection (n = 7), was followed by completion adrenalectomy. The fluorescence signal intensity dynamics were recorded and analyzed using proprietary software. For each pixel, the slope of fluorescence signal intensity evolution over time was translated into a color-coded perfusion cartography, which was superimposed onto real-time images obtained with the corresponding left and right camera systems. Quantitative fluorescence signal analysis in the regions of interest (ROIs) served to assess adrenal remnant perfusion in divided adrenal glands. RESULTS: In the retroperitoneum, the vascular anatomy was illuminated in fluorescence imaging first. The adrenal glands were promptly highlighted after primary intravenous ICG administration (n = 9) or showed a fluorescence signal intensity increase upon reinjection (n = 3). Quantitative fluorescence analysis showed a statistically significant difference between perfused and ischemic segments in divided glands (p = 0.0156). CONCLUSIONS: Fluorescence imaging provides real-time guidance during minimally invasive adrenal surgery. Prior to dissection, it allows to easily discriminate the adrenal gland from surrounding retroperitoneal structures. After adrenal gland division, ICG injection associated with a computer-assisted quantitative analysis helps to distinguish between well-perfused and ischemic segments. Further studies are underway to establish the correlation between remnant perfusion and viability.

Transcutaneous laryngeal ultrasonography (TLUS) as an alternative to direct flexible laryngoscopy (DFL) in the perioperative evaluation of the vocal cord mobility in thyroid surgery.

PURPOSE: Direct flexible laryngoscopy (DFL) is the golden standard to evaluate the vocal cord (VC) function in thyroid and parathyroid surgery pre- and postoperatively. Transcutaneous laryngeal ultrasonography (TLUS) could represent an alternative to the DFL and has been evaluated in the present study comparing the results of both methods performed at two referral centers for endocrine pathologies. METHODS: In the setting of a retrospective study, 668 patients (560 female, 118 male; mean age 50.3 ± 14.2) were included from two tertiary referral centers of endocrine surgery. In all patients, TLUS was performed pre- and postoperatively prior to transnasal DFL, which served as a golden standard. TLUS was performed by B-scan (probe 5-13 MHz, aperture 40 mm). RESULTS: Preoperative visualization of the vocal cords by TLUS was possible in 526 patients (78.7%). Due to the frequent thyroid cartilage calcification (TCC) in male patients, a significant difference in the visualization rate was found between female and male (88.7% vs. 26.8%) [p < 0.0001]. Additionally, the visualization rate was inversely related to the patient's age [p < 0.001]. The sensitivity of preoperative TLUS was found to be 66.7%, the specificity 100%. DFL confirmed a postoperative palsy in 34 out of 40 patients with supposed abnormal vocal cord mobility at TLUS and demonstrated a palsy in four more cases with supposed regular mobility at TLUS. Therefore, the sensitivity of postoperative TLUS was 86%, the specificity of 99.1%, positive predictive value 89.4%, negative predictive value 98.7%. CONCLUSIONS: TLUS could represent an alternative for the evaluation of vocal cords mobility. This method has the potential to replace the DFL in the majority of cases, especially in female patients. Nevertheless, DFL is still necessary in about 20% of the patients with failed visualization at TLUS.

Minimally Invasive Surgery (MIS) in Children and Adolescents with Pheochromocytomas and Retroperitoneal Paragangliomas: Experiences in 42 Patients.

BACKGROUND: Pheochromocytomas (PH) and paragangliomas (PGL) are rare tumours in children accounting for about 1% of the paediatric hypertension. While minimally invasive surgical techniques are well established in adult patients with PH, the experience in children is extremely limited. To the best of our knowledge, we herewith present the largest series of young patients operated on chromaffin tumours by minimally invasive access. MATERIALS: In the setting of a prospective study (1/2001-12/2016), 42 consecutive children and adolescents (33 m, 9 f) were operated on. Thirty-seven patients (88%) suffered from inherited diseases. Twenty-six patients had PH, 11 presented retroperitoneal PGL, and five patients suffered from both. Altogether, 70 tumours (mean size 2.7 cm) were removed (45 PH, 25 PGL). All operations were performed by a minimally invasive access (retroperitoneoscopic, laparoscopic, extraperitoneal). Partial adrenalectomy was the preferred procedure for PH (31 out of 39 patients). Twenty patients received α-receptor blockade preoperatively. RESULTS: One patient died after induction of anaesthesia due to cardiac arrest. All other complications were minor. Conversion to open surgery was necessary in two cases with PGL. Median operating time for unilateral PH was 55 min, in bilateral cases 125, 143 min in PGs, and 180 min in combined cases. Median blood loss was 20 ml (range 0-1000). Blood transfusion was necessary in two cases. Intraoperative, systolic peak pressure was 170 ± 39 mmHg with α-receptor blockade and 191 ± 33 mmHg without α-receptor blockade (p = 0.41). The median post-operative hospital stay was 3 days. After a mean follow-up of 8.5 years, two patients presented ipsilateral recurrence (after partial adrenalectomy). All patients with bilateral PH (n = 13) are steroid independent post-operatively. CONCLUSIONS: PH and PGL in children and adolescents should preferably be removed by minimally invasive surgery. Partial adrenalectomy provides long-term steroid independence in bilateral PH and a low rate of (ipsilateral) recurrence. α-Receptor blockade may not be necessary in these patients.

The impact of type and number of bowel resections on anastomotic leakage risk in advanced ovarian cancer surgery.

OBJECTIVE: To identify risk factors for anastomotic leakage (AL) in patients undergoing primary advanced ovarian cancer surgery and to evaluate the prognostic implication of AL on overall survival in these patients. METHODS: We analyzed our institutional database for primary EOC and included all consecutive patients treated by debulking surgery including any type of full circumferential bowel resection beyond appendectomy between 1999 and 2015. We performed logistic regression models to identify risk factors for AL and log-rank tests and Cox proportional hazards models to evaluate the association between AL and survival. RESULTS: AL occurred in 36/800 (4.5%; 95% confidence interval [3%-6%]) of all patients with advanced ovarian cancer and 36/518 (6.9% [5%-9%]) patients undergoing bowel resection during debulking surgery. One hundred fifty-six (30.1%) patients had multiple bowel resections. In these patients, AL rate per patient was only slightly higher (9.0% [5%-13%]) than in patients with rectosigmoid resection only (6.9% [4%-10%]), despite the higher number of anastomosis. No independent predictive factors for AL were identified. AL was independently associated with shortened overall survival (HR 1.9 [1.2-3.4], p=0.01). CONCLUSION: In the present study, no predictive pre- and/or intraoperative risk factors for AL were identified. AL rate was mainly influenced by rectosigmoid resection and only marginally increased by additional bowel resections.

Posterior retroperitoneoscopic adrenal surgery for clinical and subclinical Cushing's syndrome in patients with bilateral adrenal disease.

BACKGROUND: The treatment of hypercortisolism for patients with bilateral adrenal disease (BAD) is controversial. Bilateral total adrenalectomy results in permanent hypocortisolaemia requiring lifelong steroid replacement. A more conservative surgical approach, with less than bilateral total adrenalectomy (leaving functional adrenal tissue either unilaterally or bilaterally), represents an alternative option; however, long-term outcome or recurrence data are limited. We report our experience with the surgical management of hypercortisolism caused by BAD. METHODS: Between 2004 and 2016, 42 patients (12 male, 30 female; mean age 58 ± 10 years) with clinical or subclinical Cushing's syndrome (CS/sCS) caused by BAD underwent adrenal surgery via the posterior retroperitoneoscopic approach. Adrenal surgery was defined as "adrenalectomy" when total gland excision was performed or "resection" when a partial or subtotal adrenal resection was performed. Clinical, radiological and biochemical parameters were evaluated preoperatively and postoperatively. RESULTS: Seventy adrenal operations performed in total included unilateral resection (n = 3), unilateral adrenalectomy (n = 15), bilateral resection (n = 9), adrenalectomy and contralateral resection (n = 14) and bilateral total adrenalectomy (n = 3). Median operating time was 47.5 min (30-150) with no difference between unilateral and bilateral (synchronous included) procedures (p = 0.15). Mortality was zero. Clavien-Dindo grade of postoperative complications was I (n = 5) and IV (n = 3). All but one patient with CS and 17/31 patients with sCS received postoperative steroid supplementation for a median duration of 20 (1.5-129) months. After median follow-up of 40 months (3-129), the remission rate was 92%; 11 patients required ongoing steroid supplementation. There were three biochemical recurrences (two underwent contralateral resection); two patients with new/progressive radiological nodularity are biochemically eucortisolaemic. A significant reduction in BMI (p = 0.01) and antihypertensive requirements (p = 0.04) was observed postoperatively. CONCLUSION: A surgical approach which facilitates the conservation of functional adrenal tissue represents a suitable strategy for hypercortisolism caused by BAD. This approach avoids the necessity for lifelong steroid replacement in the majority of cases with low rates of adrenal insufficiency and recurrence.

Local recurrence in the neck and survival after thyroidectomy for metastatic renal cell carcinoma.

BACKGROUND: Most investigations of thyroidectomy for metastatic renal cell carcinoma (RCC) are case studies or small series. This study was conducted to determine the contribution of clinical and histopathologic variables to local recurrence in the neck and overall survival after thyroidectomy for RCC metastases. METHODS: The medical records of 140 patients with thyroidectomy for metastatic RCC performed between 1979 and 2012 at 25 institutions in Germany and Austria were analyzed. RESULTS: The median interval between nephrectomy and thyroidectomy was 120 months. Concurrence of thyroid and pancreatic metastases was present in 23 % of the patients and concurrence of thyroid and adrenal metastases in 13 % of the patients. Clinical outcome data were available for 130 patients with a median follow-up period of 34 months. The 5-year overall survival rate was 46 %, and 28 % of patients developed a local neck recurrence at a median of 12 months after thyroidectomy. Multivariate analysis showed that invasion of adjacent cervical structures (hazard ratio [HR] 3.2; p = 0.001), patient age exceeding 70 years (HR 2.5; p = 0.004), and current or past evidence of metastases to nonendocrine organs (HR 2.4; p = 0.003) were independent determinants of inferior overall survival. Conversely, invasion of adjacent cervical structures (HR 12.1; p < 0.0001) and year of thyroidectomy (HR 5.7 before 2000; p < 0.0001) were shown to be independently associated with local recurrence in the neck by multivariate analysis. CONCLUSIONS: Although significant improvement of local disease control in patients with thyroid metastases of RCC has been achieved during the last decade, overall outcome continues to be poor for patients with locally invasive thyroid metastases.

Comprehensive re-sequencing of adrenal aldosterone producing lesions reveal three somatic mutations near the KCNJ5 potassium channel selectivity filter.

BACKGROUND: Aldosterone producing lesions are a common cause of hypertension, but genetic alterations for tumorigenesis have been unclear. Recently, either of two recurrent somatic missense mutations (G151R or L168R) was found in the potassium channel KCNJ5 gene in aldosterone producing adenomas. These mutations alter the channel selectivity filter and result in Na(+) conductance and cell depolarization, stimulating aldosterone production and cell proliferation. Because a similar mutation occurs in a mendelian form of primary aldosteronism, these mutations appear to be sufficient for cell proliferation and aldosterone production. The prevalence and spectrum of KCNJ5 mutations in different entities of adrenocortical lesions remain to be defined. MATERIALS AND METHODS: The coding region and flanking intronic segments of KCNJ5 were subjected to Sanger DNA sequencing in 351 aldosterone producing lesions, from patients with primary aldosteronism and 130 other adrenocortical lesions. The specimens had been collected from 10 different worldwide referral centers. RESULTS: G151R or L168R somatic mutations were identified in 47% of aldosterone producing adenomas, each with similar frequency. A previously unreported somatic mutation near the selectivity filter, E145Q, was observed twice. Somatic G151R or L168R mutations were also found in 40% of aldosterone producing adenomas associated with marked hyperplasia, but not in specimens with merely unilateral hyperplasia. Mutations were absent in 130 non-aldosterone secreting lesions. KCNJ5 mutations were overrepresented in aldosterone producing adenomas from female compared to male patients (63 vs. 24%). Males with KCNJ5 mutations were significantly younger than those without (45 vs. 54, respectively; p<0.005) and their APAs with KCNJ5 mutations were larger than those without (27.1 mm vs. 17.1 mm; p<0.005). DISCUSSION: Either of two somatic KCNJ5 mutations are highly prevalent and specific for aldosterone producing lesions. These findings provide new insight into the pathogenesis of primary aldosteronism.

Is minimally invasive, video-assisted thyroidectomy feasible in Graves' disease?

BACKGROUND: Although the safety and advantages of minimally invasive, video-assisted thyroidectomy (MIVAT) are well documented in nodular thyroid disease, its role in Graves' disease is controversial. We compared the outcomes of patients undergoing MIVAT with those undergoing conventional thyroidectomy for Graves' disease. METHODS: Of the 497 patients with Graves' disease referred for surgery (1999-2009), 157 (31.6%) patients underwent the MIVAT procedure (video-assisted group). As a control group, 340 patients undergoing conventional thyroidectomy (conventional thyroidectomy group) were included in the current analysis. MIVAT was proposed if the thyroid volume was ≤ 30 mL. The data were obtained through a prospectively maintained surgical database. RESULTS: Most patients in both groups underwent total thyroidectomy (98% in the MIVAT group and 96.5% in the conventional group). Three (1.9%) conversions to open surgery occurred in the video-assisted group. Hospital stay was significantly shorter (P = .008) in the video-assisted group (2.1 ± 0.4 days) compared with the conventional thyroidectomy group (2.4 ± 1.4 days). The mean operative time was shorter (84 ± 29 min; range, 15-240) for the video-assisted group compared with the conventional thyroidectomy group (94 ± 43 min; range, 20-360), although this difference was not statistically significant (P = .05). Postoperative transient hypocalcemia occurred in 14 (8.9%), transient recurrent laryngeal nerve palsy occurred in 2 (1.3%), and postoperative hematoma occurred in 5 (3.2%) patients in the video-assisted group compared with 23 (6.8%), 11 (3.2%), and 8 (2.3%) patients in the conventional thyroidectomy group, respectively (P = ns). CONCLUSION: In selected patients with Graves' disease, MIVAT is feasible and can be performed safely with results comparable with open surgery.

Video-assisted bilateral neck exploration in patients with primary hyperparathyroidism and failed localization studies.

BACKGROUND: In primary hyperparathyroidism (pHPT) positive preoperative localization studies are accepted as a precondition for applying minimally invasive surgical techniques. Without localization, open bilateral neck exploration (BNE) is considered the standard option. The present study analyzes the feasibility and effectiveness of minimally invasive video-assisted BNE in patients with pHPT and negative or discordant localization studies. METHODS: From a prospective series of 380 minimally invasive video-assisted parathyroidectomies (MIVAP) performed in 367 patients for pHPT (1999-2009), 68 patients (10 male, 58 female; mean age: 58 years) were selected. These patients had failed localization studies and underwent BNE with the MIVAP technique. Operative time, complications, conversions to open technique, and cure rate were determined. RESULTS: Mean operative time was 52 +/- 26 min (range: 20-180 min). MIVAP with BNE was successfully completed in 66 (97%) patients with two conversions to open technique. Recurrent laryngeal nerve palsy occurred in one patient. Biochemical cure was achieved in 67 patients (98.5%), in 65 patients (95.5%) after the first operation and in two more patients by video-assisted re-exploration on the first postoperative day. One patient remained with persistent disease even after repeated open BNE. CONCLUSIONS: In experienced hands, video-assisted BNE with the MIVAP technique, for pHPT and failed localization studies, is feasible, safe, and gives results equivalent to the conventional open technique.

Posterior retroperitoneoscopic adrenalectomy for clinical and subclinical Cushing's syndrome.

BACKGROUND: Because of co-morbidity, adrenalectomy for adrenal Cushing's syndrome may be associated with an increased complication rate and long operating times. In the present study we report our experience with the posterior retroperitoneoscopic adrenalectomy in a large group of patients with clinical or subclinical Cushing's syndrome. PATIENTS AND METHODS: Between July 1994 and June 2009, 170 patients (17 males, 153 females age 50 +/- 13 years; range: 12-78 years) affected by Cushing's syndrome underwent operation via posterior retroperitoneoscopic access. Patients were divided into two groups, those with manifest Cushing's syndrome (mCS) [99 patients: 6 male, 93 female; age 45 +/- 13 years] and those with subclinical Cushing's syndrome (sCS) [71 patients: 11 male, 60 female; age: 56 +/- 11 years]. The sCS classification was assumed in cases without typical clinical symptoms but with a pathological dexamethasone suppression test. Partial adrenalectomy was performed in 35 cases (24 in the mCS-group and 11 in the sCS-group). RESULTS: Mortality was zero; major complications did not occur. The incidence of postoperative minor complications was 5.3%. Mean operating time was 58 +/- 36 min (range: 20-230 min) and did not differ between mCS and sCS patients (58 versus 59 min; p = ns). Postoperative oral steroids supplementation (POSS) was administered in 136 patients (99 mCS, 37 sCS). If POSS was started, mean duration of therapy was 12.3 months (mCS) and 10.3 months (sCS) [p = 0.08], respectively. After a mean follow-up of 70.9 +/- 46.5 months the cure rate was 99.4%. CONCLUSIONS: The posterior retroperitoneoscopic approach is fast and safe even in patients with Cushing's syndrome. Partial adrenalectomy represents a new option in the treatment of cortisol-producing adenomas.