Costanza Chiapponi

The aim of the present study is to discuss the benefits of intraoperative frozen sections (FS) for the surgical management of endocrine tumors. A systematic search of the literature of the last ten years on FS in the field of oncologic endocrine surgery was carried out and a discussion based on the available evidence and experience of the authors is provided. A group of publications focused on the role of intraoperative FS in thyroid surgery in identifying the malignant potential of thyroid nodules. The detection of lymph node metastasis and extrathyroidal growth in differentiated thyroid cancer (DTC) were also two other topical groups as well as the diagnosis of lymph node involvement based on stromal desmoplasia in medullary thyroid cancer (MTC). A further group investigated the possibilities of deep learning to overcome technical problems and another investigated the cost-benefit analyses. There is no relevant literature on the role of FS in the surgical treatment of parathyroid and adrenal cancers. The synthesis of the available evidence suggests that FS investigations of the thyroid glands should be restricted to Bethesda V nodules. The technical limitations in the exclusion of vascular and capsular invasion make the FS unsuitable for follicular neoplasms and oncocytic lesions. The Delphi lymph node seems to be suitable for investigation using FS and when positive represents an indication for lymphadenectomy in cN0 patients. Larger studies are necessary in the future to confirm if the absence of desmoplasia with an intact tumor capsule can reliably justify omitting lymph node resection in MTC, independent of the calcitonin level. The costs and benefits depend on the individual context so that generalization is difficult. Deep learning models could generally improve the performance of FS analysis in the future. In thyroid surgery awareness of the technical limitations of FS is crucial for correct implementation and thus to optimize its performance. A preoperative fine needle biopsy and surgical experience help in selecting the nodules that can benefit from FS. Deep image learning could help to overcome current problems in the future. In adrenal and parathyroid oncologic surgery FS do not play a relevant role.

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.

Zusammenfassung Hintergrund Das molekulare Profiling ist derzeit in Deutschland noch nicht verbreitet und seine Möglichkeiten, solitäre Schilddrüsenknoten personalisiert zu behandeln, nicht ausgeschöpft. Methode Narrative Bewertung der verfügbaren Optionen und deren Evidenz auf der Basis der aktuellen internationalen Literatur sowie Diskussion der möglichen Anwendungen im deutschen Kontext aus Sicht eines Schilddrüsenchirurgen und eines -pathologen. Ergebnisse Die vor allem in US-amerikanischen Raum verfügbaren kommerziellen Tests für molekulares Profiling von Schilddrüsenknoten bieten gute Rule-in- und etwas schlechtere Rule-out-Möglichkeiten, da viele differenzierte Schilddrüsenkarzinome keine genetischen Alterationen aufweisen. Die Kosten dieser Tests und der molekularen Pathologie für Knotenabklärung sind noch hoch und die einzelnen Mutationen noch nicht eindeutig charakterisiert. Diskussion Es ist davon auszugehen, dass das molekulare Profiling in den nächsten Jahren an Bedeutung gewinnen und einen Weg in die klinische Routine finden wird. Zum jetzigen Zeitpunkt ist die Evidenz der klinischen Bedeutung der meisten Mutationen der Schilddrüsenkarzinome jedoch noch nicht ausreichend, um therapeutische Konsequenzen daraus abzuleiten.

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.

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.

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, PP=0.792). In multivariate analysis, advanced T (PPP=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.

Editorial Black thyroid: a note for the surgeon, the pathologist and the dermatologist Costanza Chiapponi, Anne Maria Schultheis