Piermarco Papini

Background/Objectives: Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was reclassified as a non-malignant entity in 2016 to reduce overtreatment. A proportion of NIFTP-containing glands nonetheless harbour a synchronous differentiated thyroid carcinoma (DTC). We quantified its prevalence and pathological profile and assessed whether routinely collected pre-operative variables identify affected patients. Methods: A multicentre retrospective cohort of 1185 adults with NIFTP confirmed at second histological review, operated on between 2017 and 2023 in 22 centres. The outcome was a synchronous DTC in the surgical specimen. A weighted random forest and an elastic-net logistic regression based on 13 pre-operative predictors were evaluated with 20-times repeated five-fold cross-validation, with all data-driven steps nested within training folds, and with leave-one-centre-out and temporal validation. Results: A synchronous DTC was present in 61 patients (5.1%; 95% CI 4.0–6.6; 6.2% after review of the stored reports), with marked between-centre variation (none recorded in eight centres). Fifty-eight carcinomas (95%) were pT1a; none had gross extra-thyroidal extension or nodal metastasis (nodes examined in 27 patients), and none met the 2025 American Thyroid Association criteria mandating a more extensive operation. No pre-operative variable differed between groups after multiplicity adjustment. The cross-validated AUROC was 0.56 (95% CI 0.47–0.65) for the random forest and 0.58 (0.48–0.67) for the elastic net; the within-centre concordance was 0.48 and the temporal-validation AUROC 0.39, and decision-curve analysis showed no net benefit over default strategies. Conclusions: About one in twenty NIFTP-containing specimens harbours a synchronous DTC, usually a low-risk papillary microcarcinoma. Routinely available pre-operative variables do not identify these patients; management should be guided by the pathology of the carcinoma itself.

Background: The suitability of minimally invasive adrenalectomy (MIA) for adrenal tumors ≥6 cm remains debated due to technical challenges and oncological concerns. This study aimed to assess the safety and feasibility of MIA for large adrenal tumors by comparing surgical outcomes with smaller tumors. Methods: This retrospective cohort study included 269 patients who underwent MIA (2013–2023), divided into two groups: Group A (p = 0.031). Bilateral procedures and a higher Charlson comorbidity index were associated with longer LOS (p < 0.001 and p = 0.015, respectively). Conclusions: MIA is a safe and feasible approach for tumors ≥6 cm, despite being associated with a higher conversion rate.

Background: The suitability of minimally invasive adrenalectomy (MIA) for adrenal tumors ≥6 cm remains debated due to technical challenges and oncological concerns. This study aimed to assess the safety and feasibility of MIA for large adrenal tumors by comparing surgical outcomes with smaller tumors. Methods: This retrospective cohort study included 269 patients who underwent MIA (2013–2023), divided into two groups: Group A (< 6 cm, n=197) and Group B (≥6 cm, n=72). The primary endpoint was the postoperative complication rate; secondary endpoints included conversion to open surgery and postoperative length of stay (LOS). Results: Multivariate analysis identified no factors associated with postoperative complications, whereas tumor size ≥6 cm was associated with conversion to open surgery (p=0.031). Bilateral procedures and a higher Charlson comorbidity index were associated with longer LOS (p< 0.001 and p=0.015, respectively). Conclusion: MIA is a safe and feasible approach for tumors ≥6 cm, despite being associated with a higher conversion rate.

Background: Parathyroid gland (PG) surgery is often challenging due to the small size and indistinct nature of these glands. The introduction of intraoperative near-infrared autofluorescence (NIRAF) has shown promise in localizing parathyroid tissue. However, the NIRAF features of parathyroid adenomas remain unclear. The aim of this study is to assess the NIRAF pattern of parathyroid adenomas. Methods: Patients who underwent surgery for primary hyperparathyroidism at the University Hospital of Pisa, Endocrine Surgery Unit, between December 2021 and February 2022 were enrolled in this study. Intraoperative NIRAF patterns of suspected parathyroid adenomas were evaluated, with particular attention given to the presence of a bright cap. Results: A retrospective study was conducted on 11 patients with primary hyperparathyroidism who underwent parathyroidectomy at our institution. Histopathological examination of the 15 resected specimens confirmed 14 parathyroid adenomas (12 chief cell parathyroid adenomas, 1 oxyphil cell parathyroid adenoma, and 1 mixed cell parathyroid adenoma) and one schwannoma. All adenomas exhibited a heterogeneous NIRAF pattern, distinct from the homogeneous pattern observed in the schwannoma. A bright cap was identified in 9 out of 14 (64.3%) parathyroid adenomas (all chief cell adenomas). On the contrary, all 9 macroscopically normal PGs identified during surgery presented an homogeneous pattern. Conclusion: Our findings support the integration of NIRAF into parathyroid surgical procedures. The heterogeneous NIRAF pattern observed in parathyroid adenomas, often accompanied by a bright cap, offers a promising intraoperative diagnostic tool to differentiate hyperfunctioning from normal parathyroid tissue. Larger-scale randomized trials are warranted to further validate these findings.

Purpose: Assessing vocal cord mobility is crucial for patients undergoing thyroid surgery. We aimed to evaluate the feasibility and efficacy of surgeon-performed transcutaneous laryngeal ultrasound (TLUS) compared to flexible nasolaryngoscopy. Method: From February 2022 to December 2022, we conducted a prospective observational study on patients scheduled for total thyroidectomy at our Institution. All patients underwent TLUS followed by flexible nasolaryngoscopy by a blinded otolaryngologist. Findings were classified as normal or vocal cord movement impairment and then compared. Patients evaluable on TLUS were included in Group A, while those not evaluable were included in Group B, and their features were compared. Results: Group A included 180 patients, while Group B included 21 patients. Male sex (p < 0.001), age (p = 0.034), BMI (p < 0.001), thyroid volume (p = 0.038), and neck circumference (p < 0.001) were associated with Group B. TLUS showed a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100%, 99.4%, 94.4%, 100%, and 99.4%, respectively. Cohen’s K value was 0.984. Conclusion: TLUS is a valid, easy-to-perform, non-invasive, and painless alternative for evaluating vocal cords in selected patients. It can be used either as a first level exam and as screening tool for selecting cases for flexible nasolaryngoscopy. TLUS should be integrated into routine thyroid ultrasound examination.

Background: The use of robot‐assisted transaxillary thyroidectomy (RATT) has rapidly spread in the last 2 decades, although it is mostly limited to Asian countries.Method: We retrospectively enroled all patients with histologic diagnoses of thyroid cancer who underwent RATT at the University Hospital of Pisa from May 2012 to September 2020.Results: The study included 242 patients; 128 (47%) underwent total thyroidectomy and 114 (53%) underwent thyroid lobectomy, among which 28 patients (24.6%) required completion thyroidectomy. Radioactive iodine ablation therapy was required in 90 patients (37%). The complication rate was 5.3%. After a median follow‐up of 38 months, an excellent response to therapy was achieved in 107 patients (74%), whereas the response was indeterminate in 12 (8%) and incomplete in 16 (11%). No local or distant relapses or increases in thyroglobulin or antibody levels were documented.Conclusions: In experienced hands, RATT represents a valid option for the treatment of thyroid cancer in selected cases.

Robot-assisted transaxillary thyroidectomy is widely performed in Asian countries, although it is still under discussion in the Western World. However, there have been few studies reporting on the learning curve of robot-assisted transaxillary thyroidectomy. We used the cumulative sum (CUSUM) analysis to assess the learning curve of gasless robot-assisted transaxillary thyroidectomy at a third-level institution in Europe. We included all consecutive patients operated by a single surgeon without previous experience of robotic surgery from February 2012 to January 2023. The primary endpoint of the study was the learning curve extracted from the median operative time using the CUSUM method for the quantitative assessment. Overall, 583 patients were enrolled. The median operative time for thyroid lobectomy and total thyroidectomy was 70 and 90 min, respectively. The CUSUM analysis showed that the learning curve for thyroid lobectomy and total thyroidectomy is 66 and 56 cases, respectively. Moreover, the presence of thyroiditis resulted associated with shorter operative time for total thyroidectomy (p = 0.044), whereas no factors resulted associated with surgical complications. The learning curve for performing robotic transaxillary thyroid lobectomy for a surgeon without previous robotic experience is 66 cases. After that, 56 cases must be performed to acquire proficiency in robotic transaxillary total thyroidectomy. Training programs may reduce the slope of the learning curve.