Intraoperative thyroid frozen section: indications, results and consequences.

Background: Frozen section (FS) analysis is strongly influenced by the experience of surgeons and pathologists. We analyzed its performance in a secondary care hospital with surgical and pathologic experience transferred from a university hospital. Methods: Indications, results, and consequences of all thyroid FS performed between January 1, 2021 and December 31, 2022 were critically reviewed. Results: FS was performed in 90 (26.5%) of 340 procedures. Indications consisted in a suspicious fine needle biopsy in 28 (31.1%) cases, (99m) Technetium-Methoxy-Isobutyl-Isonitrile (MIBI) retaining hypofunctional nodules in 25 (27.8%), the intraoperative appearance in 18 (20%), the sonographic appearance in 18 (20%) and a positron emission tomography (PET) positive result in 1 case (1.1%). Malignancy was diagnosed in 21 (23.3%) and confirmed by final histology in all cases (100%). In the remaining 69 (76.7%) FS displaying no positive malignancy criteria, final histology delivered benign in 62 (89.8%) and malignant diagnoses in 7 cases (10.1%). 25% of thyroid carcinomas could not be diagnosed by FS. FS sensitivity was consequently 75% (95% CI: 55.1-89.3%). All missed malignancies were papillary thyroid carcinomas of follicular variant (fvPTC). FS sensitivity was lowest in MIBI positive hypofunctional nodules (33%) and Bethesda III (50%) as opposed to Bethesda V (92.9%) and to those cases with suspicious sonographic or intraoperative appearance (71.4%). Two-staged surgery was necessary in 10 (15.8%) of carcinomas. Conclusions: Sensitivity of FS in a secondary care hospital offering surgical and pathologic experience from a specialized university center is 75% and mainly reduced by the prevalence of fvPTC. Omitting FS in Bethesda III and MIBI positive hypofunctional nodules might improve FS performance.

TERT RNAscope analysis of sub-centimetric papillary thyroid carcinomas and synchronous lymph node metastases.

BACKGROUND: Sub-centrimetric papillary thyroid carcinomas usually have a good prognosis with a cancer specific survival of > 99%, however in up to 65% of patients, lymph node metastases can be observed. Molecular alterations in BRAF, TERT and TP53 are associated with worse clinicopathological outcome in patients with papillary thyroid carcinoma. MATERIAL AND METHODS: Twenty-two cases of papillary thyroid carcinomas measuring ≤ 1 cm with synchronous lymph node metastases were examined regarding morphological patterns and immunohistochemical status of p53, Ki-67, and BRAF V600E status. TERT RNA expression in lymph node metastases were evaluated by RNAScope®. RESULTS: Morphological patterns were heterogeneous in both primary tumors and lymph node metastases. Proliferation indices measured by Ki-67 were low. Both primary and lymph node metastases were wild type for p53 by immunohistochemical analysis. No lymph node metastasis showed TERT expression by RNAScope®. CONCLUSIONS: Our data indicate that TERT expression is not involved in the development early lymph node metastasis in patients with sub-centimetric PTC.

The Impact of the COVID Pandemic on Adrenal Surgery at an Academic Endocrine Surgery Unit.

COVID-19 has severely affected the delivery of surgical care worldwide. The aim of the present study was to evaluate its impact on adrenal surgery at our academic endocrine center. All primary adrenal surgeries performed at the University Hospital of Cologne, Germany between 01.01.2019 and 31.07.2022 were included. This time frame was divided into pre-Covid (before 02/20), acute Covid (until 05/21), and post acute period (after 05/2021). Demographics, clinic-pathologic characteristics and treatment of these patients were analyzed. One hundred adrenalectomies were included: 22 before, 30 during, and 48 after the acute phase. The percentage of Conn adenomas and pheochromocytomas decreased during the acute phase (from 45.4 to 26.6% and from 18 to 10%, respectively) in favor of Cushing adenomas and suspicious tumors (from 4.5 to 20% and from 31.8 to 36.6%). About 90.9% of tumors resected for suspicion of malignancy were confirmed malignant by final histopathology, as opposed to 71.4% and 52.6% before and after the acute phase. The operative technique was similar during the three phases (63% retroperitoneoscopic, 34% laparoscopic and 2% open resections), with a significantly shorter operative time for retroperitoneoscopy (p=0.04). ICU monitoring demand increased during the acute phase (from 13.6% to 43.3%), according to the increase in Cushing adenomas and malignant tumors. During the acute phase of COVID-19 pandemic adrenal surgery for Cushing and malignant tumors increased, while a delay in pheochromocytoma surgery to the post acute phase was observed. The suspicion of malignancy formulated by the endocrine tumor board was accurate in 90.9% of cases.

Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study.

BACKGROUND: Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours. METHODS: In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186. FINDINGS: Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6-3·4]) compared with the prepandemic phase (2·0 [0·9-3·7]; p<0·0001) and pandemic decrease phase (2·3 [1·0-5·0]; p<0·0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69·0%] of 3704 vs 1515 [71·5%] of 2119; OR 1·1 [95% CI 1·0-1·3]; p=0·042), lymph node metastases (343 [9·3%] vs 264 [12·5%]; OR 1·4 [1·2-1·7]; p=0·0001), and tumours at high risk of structural disease recurrence (203 [5·7%] of 3584 vs 155 [7·7%] of 2006; OR 1·4 [1·1-1·7]; p=0·0039). INTERPRETATION: Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation. FUNDING: None.

Extension of resection after positive intraoperative pathology during surgery for gastric and gastroesophageal junction adenocarcinoma: a retrospective cohort study.

BACKGROUND: Residual tumor at the resection margins after surgery for gastric and gastroesophageal junction (GEJ) adenocarcinoma is a known prognostic factor. In this single-center, retrospective cohort study in a tertiary referral center, the authors aimed to evaluate the relevance of intraoperative pathology consultation (IOC) and consecutive extension of surgery on patient survival. STUDY DESIGN: Of 737 consecutive patients undergoing (sub)total gastrectomy for gastric or GEJ adenocarcinoma, 679 cases with curative intent surgery between 05/1996 and 03/2019 were included. Patients were categorized into: R0 without further resection (direct R0), R0 after positive IOC and extension of resection (converted R0), and R1. RESULTS: IOC was performed in 242 (35.6%) patients, in 216 (89.3%) at the proximal resection margin. Direct R0-status was achieved in 598 (88.1%), converted R0 in 26 (3.8%) of 38 (5.6%) patients with positive IOC and R1 in 55 (8.1%) patients. The median follow-up was 29 months for surviving patients. 3-year survival rate (3-YSR) was significantly higher for direct R0 compared to converted R0 with 62.3% compared to 21.8% (hazard ratio=0.298; 95% CI=0.186-0.477, P <0.001). 3-YSR was similar between converted R0 and R1 (21.8 vs. 13.3%; hazard ratio =0.928; 95% CI=0.526-1.636, P =0.792). In multivariate analysis, advanced T ( P <0.001), N ( P <0.001), R ( P =0.003), and M1 status ( P <0.001) were associated with worse overall survival. CONCLUSION: IOC and consecutive extended resection for positive resection margins in gastrectomy for the proximal gastric and GEJ adenocarcinoma does not achieve long-term survival benefits in advanced tumor stages.

Differentiated Thyroid Cancer in Adolescents: Single Center Experience and Considerations for Surgical Management and Radioiodine Treatment

Objective: Differentiated thyroid cancer (DTC) in adolescents rare but with a favorable outcome, despite higher rates of cervical lymph node and pulmonary metastasis compared to adults. The aim of this study was to critically evaluate treatment of adolescents with DTC at a single center. Methods: Patients receiving postoperative radioiodine treatment (RAIT) for DTC between 2005 and 2020 at our institution were screened to identify adolescents according to the World Health Organization definition (10-19 years of age). Demographics, clinico-pathological characteristics, treatment and outcome were analyzed. Results: Among 1,897 DTC patients, 23 (1.3%) were adolescents with a median (range) age of 16 (10-18) years. The female to male ratio was 3.6:1. Sixty percent had classic papillary thyroid cancer, with follicular variant in 40%, which was higher than previously reported (15-25%) for this age group. pT-status was pT1 in 9 (39.2%), pT2 in 8 (34.8%), pT3 in 3 (13%) and pT4 in 3 (13%) patients. In 19 (82.6%) patients, central lymphadenectomy was performed and metastasis was seen in 57%. All patients received RAIT with initial activities of 1.2 (n=1, 4.3%), 2 (n=12, 52.2%) or 3.7 GBq (n=10, 43.5%). Eighteen (78.2%) patients were free of biochemical and radiologic disease at a median follow-up of 60.7 months. Second-line surgery for lymph node relapse was necessary in 3 (13%) cases. There was one disease-associated death. Conclusion: Despite high rates of metastasis, most patients were cured, and second-line surgery was rarely required. Further prospective studies are needed to determine whether less aggressive surgical management or omitting adjuvant RAIT are feasible in patients with limited stages at diagnosis.

[Modern molecular and imaging diagnostics in pancreatic neuroendocrine neoplasms]. / Moderne molekulare und bildgebende Diagnostik bei neuroendokrinen Neoplasien des Pankreas.

BACKGROUND AND OBJECTIVE: New molecular diagnostic and radiologic imaging techniques can be used to assess the extent, risk of recurrence, prognosis and response to treatment of pancreatic neuroendocrine neoplasms (pNENs). They therefore represent a decisive help in setting the indications for surgical treatment, especially in advanced stages. METHODS: This article presents a narrative assessment of the options and evidence for modern molecular and radiologic imaging diagnostics of pNENs based on the current literature. RESULTS: While circulating DNA, circulating tumor cells and microRNAs have not yet become established in everyday clinical practice, the current literature suggests a promising role for the so-called NETest. Recent studies demonstrated its possible importance for the surgical management of pNENs. Besides [68Ga]Ga-DOTA-SSA-PET and [18]FDG-PET, which remain the gold standards for imaging NENs, radiomics represent an exciting alternative to biopsies and will possibly play an increasingly important role in the future. DISCUSSION: There are new promising alternatives to chromogranin A, which has been clinically widespread since the 1970s despite several drawbacks, to map the extent, risk of recurrence, prognosis and response to treatment of pancreatic pNENs. In terms of personalized medicine, modern molecular and radiological diagnostics should play an increasing role for indicating and planning surgical treatment and for follow-up in the future.

Subacute thyroiditis after SARS-Cov2 vaccination: A review of the cases being described and personal experience.

Objective. The present study evaluates the occurrence of subacute thyroiditis in temporal connection with SARS-Cov2 vaccinations described in the literature last year and confirmed by our clinical routine. Methods. Systematic literature search in Medline for studies reporting diagnosis of subacute thyroiditis in temporal connection with vaccinations against Covid 19. Results. The literature search yielded 24 relevant references out of which 22 were "case reports" and two "Letters to the Editor" and encompassed 37 patient cases, in total. They had received a SARS-Cov2 vaccination shortly before the diagnosis (median interval to vaccination six days). In none of these cases, infection of the upper respiratory tract had previously been identified as a classic trigger of the disease. Newly occurring hyperthyroidism and increased laboratory signs of inflammation were described in 78% and 74% of cases, respectively. Atypical clinical pictures (asymptomatic, euthyroid, no inflammation marks) have been observed in both the literature and our patients suspected of thyroid cancer referred to surgery. Conclusions. In times of pandemics and the resulting vaccination, new rapidly occurring sonographic changes in the thyroid gland should be revaluated after 2-3 weeks, or recommended to undergo a fine-needle biopsy, in order to avoid unnecessary surgical interventions.

Hürthle Cell Carcinoma: Single Center Analysis and Considerations for Surgical Management Based on the Recent Literature.

Background: Hürthle cell carcinoma (HCC) of the thyroid is rare. There are contrasting data on its clinical behavior. The aim of this study was to describe clinic-pathological features and outcomes of HCC patients at our institution, in order to adapt our surgical management. Methods: We retrospectively studied 51 cases of HCC treated at the interdisciplinary endocrine center of the University Hospital of Cologne, Germany between 2005 and 2020. Results: Patients median age was 63 years (range 29-78) with 64.7% of cases being female. Primary treatment included surgery and postoperative radioiodine therapy with 3.7 GBq in all patients. Surgery consisted of total thyroidectomy in all cases and additional central lymphadenectomy in 90.2% of cases. The median number of harvested lymph nodes was 11 (range 2-31). Lymph node involvement was found in two (4.3%) pT4a tumors. In all other cases (95.7%), central lymphadenectomy was prophylactic and lymph nodes were free of metastasis in final histopathology. Twelve (23.5%) patients with incomplete biochemical response to primary treatment were diagnosed with structural relapse during the course of disease, for which seven (58.4%) underwent resection of isolated cervical metastasis. Histopathology revealed soft tissue implants in all cases and cervical surgery led to biochemical and radiologic cure in only two (28.5%) cases. Five (41.6%) patients developed metastatic disease, followed by systemic therapy in two patients. Vascular invasion of the primary tumor was significantly associated with relapse (p<0.01). Conclusions: Recurrence of HCC was common in this study. Given the low rate of lymph node metastases both in this study and in recent literature and the nature of relapse (soft tissue instead of nodal metastasis), the benefit of routine prophylactic central lymph node dissection for HCC remains unclear, especially in the absence of vascular invasion from the primary tumor.

Targeted Therapy for Adrenocortical Carcinoma: A Genomic-Based Search for Available and Emerging Options.

In rare diseases such as adrenocortical carcinoma (ACC), in silico analysis can help select promising therapy options. We screened all drugs approved by the FDA and those in current clinical studies to identify drugs that target genomic alterations, also known to be present in patients with ACC. We identified FDA-approved drugs in the My Cancer Genome and National Cancer Institute databases and identified genetic alterations that could predict drug response. In total, 155 FDA-approved drugs and 905 drugs in clinical trials were identified and linked to 375 genes of 89 TCGA patients. The most frequent potentially targetable genetic alterations included TP53 (20%), BRD9 (13%), TERT (13%), CTNNB1 (13%), CDK4 (7%), FLT4 (7%), and MDM2 (7%). We identified TP53-modulating drugs to be possibly effective in 20-26% of patients, followed by the Wnt signaling pathway inhibitors (15%), Telomelysin and INO5401 (13%), FHD-609 (13%), etc. According to our data, 67% of ACC patients exhibited genomic alterations that might be targeted by FDA-approved drugs or drugs being tested in current clinical trials. Although there are not many current therapy options directly targeting reported ACC alterations, this study identifies emerging options that could be tested in clinical trials.

[Incidental Finding of Appendiceal Neuroendocrine Tumour]. / Zufallsbefund NEN Appendix.

With an incidence of 80%, neuroendocrine neoplasia (NEN) is the most common neoplasia of the appendix. In most cases, these tumours are diagnosed as an incidental finding after appendectomy with suspected appendicitis. They are usually highly differentiated neuroendocrine tumours. Due to their frequent location on the apex of the appendix, the NENs of the appendix are usually not the cause of the symptoms typical for appendicitis.Most patients (80-90%) receive adequate oncological treatment by laparoscopic or open appendectomy that has already been performed. However, if there are risk factors such as tumour size > 2 cm, location close to the base, angioinvasion, perforation or infiltration of neighbouring organs, proliferation index of > 2% or infiltration of the mesoappendix by more than 3 mm in the final histopathological finding, subsequent resection as an oncological right sided hemicolectomy is recommended .Due to their mostly early tumour stage at diagnosis without proven lymph node metastasis, patients with NEN of the appendix have an excellent 5-year survival rate of 70-85% across all tumour stages.

Adrenal Surgery in the Era of Multidisciplinary Endocrine Tumor Boards.

Work up of adrenal masses includes assessment of endocrine activity and malignancy risk. There is no indication for surgical removal of nonfunctional adrenal adenomas, according to the guidelines. In the present study, we aimed at evaluating the impact of a university endocrine tumor board on the quality of the indications for adrenal surgery at our institution. One hundred consecutive patients receiving primary adrenal surgery at the University Hospital of Cologne, Germany were included. Their demographics, clinic-pathologic characteristics, treatment and outcome were analyzed. In 55 (55%) cases, indication for surgery consisted in functional benign tumors, including Conn, Cushing adenomas and pheochromocytomas. Forty (40%) tumors were referred to surgery for malignancy suspicion and 5 (5%) myelolipomas were removed due to their size. Eighty-nine percent of surgeries were performed as minimally invasive procedures. Overall morbidity included two (2%) self-limiting pancreatic fistulas after left laparoscopic adrenalectomy for pheochromocytoma. All functional tumors were confirmed benign by final histology. Only 33 (82.5%) of 40 suspicious cases turned out to be malignant. Consequently, nonfunctional benign adenomas were "unnecessarily" removed in only 7 (7%) patients, with 6 (85.7%) of them having a history of extra-adrenal cancer and all of them fulfilling criteria for surgery, according to the international guidelines. In conclusion, the endocrine tumor board provided an excellent adherence to the guidelines with most surgeries being performed either for functional or malignant tumors. In nonfunctional tumors with history of extra adrenal cancer, CT guided biopsy might be considered for obviating surgery.

Anaplastic thyroid cancer: genome-based search for new targeted therapy options.

Objective: Anaplastic thyroid cancer (ATC) is one of the most lethal human cancers with meager treatment options. We aimed to identify the targeted drugs already approved by the Food and Drug Administration (FDA) for solid cancer in general, which could be effective in ATC. Design: Database mining. Methods: FDA-approved drugs for targeted therapy were identified by screening the databases of MyCancerGenome and the National Cancer Institute. Drugs were linked to the target genes by querying Drugbank. Subsequently, MyCancerGenome, CIViC, TARGET and OncoKB were mined for genetic alterations which are predicted to lead to drug sensitivity or resistance. We searched the Cancer Genome Atlas database (TCGA) for patients with ATC and probed their sequencing data for genetic alterations which predict a drug response. Results: In the study,155 FDA-approved drugs with 136 potentially targetable genes were identified. Seventeen (52%) of 33 patients found in TCGA had at least one genetic alteration in targetable genes. The point mutation BRAF V600E was seen in 45% of patients. PIK3CA occurred in 18% of cases. Amplifications of ALK and SRC were detected in 3% of cases, respectively. Fifteen percent of the patients displayed a co-mutation of BRAF and PIK3CA. Besides BRAF-inhibitors, the PIK3CA-inhibitor copanlisib showed a genetically predicted response. The 146 (94%) remaining drugs showed no or low (under 4% cases) genetically predicted drug response. Conclusions: While ATC carrying BRAF mutations can benefit from BRAF inhibitors and this effect might be enhanced by a combined strategy including PIK3CA inhibitors in some of the patients, alterations in BRAFWT ATC are not directly targeted by currently FDA-approved options.

Lymphatic Vessel Invasion in Routine Pathology Reports of Papillary Thyroid Cancer.

Purpose: It is not mandatory to report lymphatic vessel invasion in pathology reports of papillary thyroid cancer (PTC) according to the current Union for International Cancer Control (UICC) TNM (tumor, nodes, and metastases) classification. However, there is some evidence for its correlation with lymph node metastasis (LNM) and prognosis. The aim of this study was to explore the clinical implication of lymphatic vessel invasion documentation of PTC because pathology reports play a pivotal role in postsurgical clinical decision-making in endocrine tumor boards. Methods: Patients undergoing postoperative radioiodine treatment for PTC at the University Hospital of Cologne, Germany between December 2015 and March 2020 were identified. Pathology reports were screened for documentation of lymphatic vessel invasion. Demographics and clinicopathologic data of patients documented, including lymphatic vessel invasion and lymph nodal involvement were analyzed. Results: A total of 578 patients were identified and included. Lymphatic vessel invasion was reported in pathology reports of 366 (63.3%) and omitted in 112 (36.7%) patients. Positive lymphatic vessel invasion (L1) was diagnosed in 67 (18.3%) of 366 patients and was documented as absent (L0) in 299 (81.7%) patients. Lymph nodal (N) status was positive (N+) in 126 (45.6%) and negative (N0) in 150 (54.3%) of these patients. In 54 (80.6%) L1 cases N+ status and in 137 (65.6%) L0 cases N0 status was diagnosed. In 13 (19.4%) cases with L1 status, there were no LNMs (L1 N0). In total, 72 (34.4%) patients had LNM despite L0 status (L0 N+). The sensitivity and specificity of LVI reporting for LNM were 0.42 and 0.91, respectively. Conclusion: In routine pathology reports of PTC used for indication to postoperative radioiodine treatment by a German endocrine tumor board, lymphatic vessel invasion was found to be reported inconsistently and mostly as L0. L1 diagnoses, however, reliably correlated with reported LNM and might, thus, be relevant for clinical decision-making. For this reason, we advocate for standardized pathologic reassessment of lymphatic vessel invasion, in particular for cases where lymph nodes are not included in the pathologic specimen and if L0 is documented.

Clinical Presentation, Treatment, and Outcome of Parathyroid Carcinoma: Results of the NEKAR Retrospective International Multicenter Study.

OBJECTIVE: In this retrospective cohort study, we describe the clinical presentation and workup of parathyroid carcinoma (PC) and determine its clinical prognostic parameters. Primary outcome was recurrence free survival. SUMMARY BACKGROUND DATA: PC is an orphan malignancy for which diagnostic workup and treatment is not established. METHODS: Eighty-three patients were diagnosed with PC between 1986 and 2018. Disease-specific and recurrence-free survivals were estimated with the Kaplan-Meier method. Risk factors for recurrence were identified by binary logistic regression with adjustment for age and sex. Thirty-nine tumors underwent central histopathological review. RESULTS: Renal (39.8%), gastrointestinal (24.1%), bone (22.9%), and psychiatric (19.3%) symptoms were the most common symptoms. Surgical treatment was heterogeneous [parathyroidectomy [PTx)] alone: 22.9%; PTx and hemithyroidectomy: 24.1%; en bloc resection 15.7%; others 37.3%] and complications of surgery were frequent (recurrent laryngeal nerve palsy 25.3%; hypoparathyroidism 6%). Recurrence of PC was observed in 32 of 83 cases. In univariate analysis, rate of recurrence was reduced when extended initial surgery had been performed (P = 0.04). In multivariate analysis low T status [odds ratio (OR) = 2.65, 95% confidence interval (CI) 1.02-6.88, P = 0.045], N0 stage at initial diagnosis (OR = 6.32, 95% CI 1.33-30.01, P = 0.02), Ki-67 <10% (OR = 14.07, 95% CI 2.09-94.9, P = 0.007), and postoperative biochemical remission (OR = 0.023, 95% CI 0.001-0.52, P = 0.018) were beneficial prognostic parameters for recurrence-free survival. CONCLUSION: Despite a favorable overall prognosis, PC shows high rates of recurrence leading to repeated surgery and postoperative recurrent laryngeal nerve palsy and hypoparathyroidism. In view of the reduced recurrence rate in cases of extended surgery, ipsilateral completion surgery may be considered when PC is confirmed.

Gender benefit in laparoscopic surgical performance using a 3D-display system: data from a randomized cross-over trial.

BACKGROUND: The use of 3D technique compared to high-resolution 2D-4K-display technique has been shown to optimize spatial orientation and surgical performance in laparoscopic surgery. Since women make up an increasing amount of medical students and surgeons, this study was designed to investigate whether one gender has a greater benefit from using a 3D compared to a 4K-display system. METHODS: In a randomized cross-over trial, the surgical performance of male and female medical students (MS), non-board certified surgeons (NBCS), and board certified surgeons (BCS) was compared using 3D- vs. 4K-display technique at a minimally invasive training parkour with multiple surgical tasks and repetitions. RESULTS: 128 participants (56 women, 72 men) were included. Overall parkour time in seconds was 3D vs. 4K for all women 770.7 ± 31.9 vs. 1068.1 ± 50.0 (p < 0.001) and all men 664.5 ± 19.9 vs. 889.7 ± 31.2 (p < 0.001). Regarding overall mistakes, participants tend to commit less mistakes while using the 3D-vision system, showing 10.2 ± 1.1 vs. 13.3 ± 1.3 (p = 0.005) for all women and 9.6 ± 0.7 vs. 12.2 ± 1.0 (p = 0.001) for all men. The benefit of using a 3D system, measured by the difference in seconds, was for women 297.3 ± 41.8 (27.84%) vs. 225.2 ± 23.3 (25.31%) for men (p = 0.005). This can be confirmed in the MS group with 327.6 ± 65.5 (35.82%) vs. 249.8 ± 33.7 (32.12%), p = 0.041 and in the NBCS group 359 ± 52.4 (28.25%) vs. 198.2 ± 54.2 (18.62%), p = 0.003. There was no significant difference in the BCS group. CONCLUSION: 3D laparoscopic display technique optimizes surgical performance compared to the 2D-4K technique for both women and men. The greatest 3D benefit was found for women with less surgical experience. As a possible result of surgical education, this gender specific difference disappears with higher grade of experience. Using a 3D-vision system could facilitate surgical apprenticeship, especially for women.

[The value of thymectomy in the treatment of non-thymomatous myasthenia gravis]. / Der Stellenwert der Thymektomie ohne Thymom in der Therapie der Myasthenia gravis.

The value of thymectomy in the treatment of non-thymomatous myasthenia gravis has been controversially discussed. The relatively low incidence and prevalence of this disease, the inconsistent documentation in various studies and the necessity of a long-term follow-up to assess the therapeutic effects has made the generation of valid data difficult. The publication in 2016 of the MGTX trial in the New England Journal of Medicine delivered the first randomized controlled data in which patients aged 18-65 years with generalized myasthenia gravis and positive for acetylcholine receptor antibodies showed a significant benefit after surgical resection of the thymus via median sternotomy. Despite a lack of validation of the advantages of thymectomy by minimally invasive surgery from randomized controlled studies, this technique seems to positively influence the outcome of certain patient groups in a similar way. Video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracic surgery (RATS) using subxyphoidal and transcervical access routes showed not only esthetic advantages but also showed no relevant inferiority in the influence on clinical outcomes of myasthenia gravis compared to median sternotomy; however, not only the benefits and the esthetic results show differences but also the advantages in the various subtypes of myasthenia gravis show divergent prospects of success with respect to remission. The clinical spectrum of myasthenia is heterogeneous with respect to the occurrence of antibodies, the body region affected and the age of the patient at first diagnosis. Ultimately, thymectomy is an effective causal treatment of myasthenia gravis.

Radioiodine Refractory Follicular Thyroid Cancer and Surgery for Cervical Relapse.

Compared to its more common counterpart papillary thyroid cancer (PTC), follicular thyroid cancer (FTC) has a less favorable outcome, due to its higher incidence of distant metastases and advanced stages at diagnosis. Despite radioiodine (RAI) avidity, metastatic FTC often progresses after radioiodine treatment (RAIT). We aimed at evaluating the indications and outcomes of surgery for cervical relapse of radioiodine refractory FTC. Patients receiving RAIT between 2005 and 2015 at the University Hospital of Cologne, Germany, were screened. Patients with FTC were identified. Demographics, clinic-pathologic characteristics, treatment, and outcome of patients diagnosed with RAI refractory FTC, who underwent cervical surgery in the course of disease, were analyzed. FTC accounted for 8.8% of all thyroid carcinomas undergoing RAIT. In 35.2% of FTC patients, disease persisted or recurred despite a cumulative mean RAI activity of 18.7 GBq ± 11.6 (follow-up 83.5 ± 56.7 months). Distant metastases were diagnosed in 75% of these patients, as bone (57.6%), lung (54.6%), and liver metastases (12.1%). Cervical relapse occurred in 63.6% of these patients and was treated in 57.1% with surgery with, and without, external beam radiation therapy (EBRT). Despite surgery and EBRT, in 75% of patients, cervical relapse recurred again. In conclusion, surgery for cervical radioiodine refractory FTC relapse is often performed in metastatic setting. With and without EBRT, cure is rare, although metastases can appear radioiodine avid. Early biological marker and systemic treatments for these patients are still needed.

Targeted Therapy of Papillary Thyroid Cancer: A Comprehensive Genomic Analysis.

Background: A limited number of targeted therapy options exist for papillary thyroid cancer (PTC) to date. Based on genetic alterations reported by the "The Cancer Genome Atlas (TCGA)", we explored whether PTC shows alterations that may be targetable by drugs approved by the FDA for other solid cancers. Methods: Databases of the National Cancer Institute and MyCancerGenome were screened to identify FDA-approved drugs for targeted therapy. Target genes were identified using Drugbank. Genetic alterations were classified into conferring drug sensitivity or resistance using MyCancerGenome, CiViC, TARGET, and OncoKB. Genomic data for PTC were extracted from TCGA and mined for alterations predicting drug response. Results: A total of 129 FDA-approved drugs with 128 targetable genes were identified. One hundred ninety-six (70%) of 282 classic, 21 (25%) of 84 follicular, and all 30 tall-cell variant PTCs harbored druggable alterations: 259 occurred in 29, 39 in 19, and 31 in 2 targetable genes, respectively. The BRAF V600 mutation was seen in 68% of classic, 16% of follicular variant, and 93% of tall-cell variant PTCs. The RET gene fusion was seen in 8% of classic PTCs, NTRK1 and 3 gene fusions in 3%, and other alterations in <2% of classic variant PTCs. Ninety-nine of 128 (77%) FDA-approved targetable genes did not show any genetic alteration in PTC. Beside selective and non-selective BRAF-inhibitors, no other FDA-approved drug showed any frequent predicted drug sensitivity (<10%). Conclusion: Treatment strategies need to focus on resistance mechanisms to BRAF inhibition and on genetic alteration-independent alternatives rather than on current targeted drugs.