Factors Impacting Academic Productivity and Satisfaction of Surgeon-scientists: A Nationwide Survey.

OBJECTIVE: To identify factors related to research success for academic surgeons. SUMMARY BACKGROUND DATA: Many recognize mounting barriers to scientific success for academic surgeons, but little is known about factors that predict success for individual surgeons. METHODS: A phase 1 survey was emailed to department chairpersons at highly funded US departments of surgery. Participating chairpersons distributed a phase 2 survey to their faculty surgeons. Training- and faculty-stage exposures and demographic data were collected and compared with participant-reported measures of research productivity. Five primary measures of productivity were assessed including number of grants applied for, grants funded, papers published, first/senior author papers published, and satisfaction in research. RESULTS: Twenty chairpersons and 464 faculty surgeons completed the survey, and 444 faculty responses were included in the final analysis. Having a research-focused degree was significantly associated with more grants applied for (PhD, incidence rate ratio (IRR)=6.93; masters, IRR=4.34) and funded (PhD, IRR=4.74; masters, IRR=4.01) compared to surgeons with only clinical degrees (all P<0.01). Having a formal research mentor was significantly associated with more grants applied for (IRR=1.57, P=0.03) and higher satisfaction in research (IRR=2.22, P<0.01). Contractually protected research time was significantly associated with more grants applied for (IRR=3.73), grants funded (IRR=2.14), papers published (IRR=2.12), first/senior authors published (IRR=1.72), and research satisfaction (Odds ratio=2.15) (all P<0.01). The primary surgeon-identified barrier to research productivity was lack of protection from clinical burden. CONCLUSIONS: Surgeons pursuing research-focused careers should consider the benefits of attaining a research-focused degree, negotiating for contractually protected research time, and obtaining formal research mentorship.

Molecular signature incorporating the immune microenvironment enhances thyroid cancer outcome prediction.

Genomic and transcriptomic analysis has furthered our understanding of many tumors. Yet, thyroid cancer management is largely guided by staging and histology, with few molecular prognostic and treatment biomarkers. Here, we utilize a large cohort of 251 patients with 312 samples from two tertiary medical centers and perform DNA/RNA sequencing, spatial transcriptomics, and multiplex immunofluorescence to identify biomarkers of aggressive thyroid malignancy. We identify high-risk mutations and discover a unique molecular signature of aggressive disease, the Molecular Aggression and Prediction (MAP) score, which provides improved prognostication over high-risk mutations alone. The MAP score is enriched for genes involved in epithelial de-differentiation, cellular division, and the tumor microenvironment. The MAP score also identifies aggressive tumors with lymphocyte-rich stroma that may benefit from immunotherapy. Future clinical profiling of the stromal microenvironment of thyroid cancer could improve prognostication, inform immunotherapy, and support development of novel therapeutics for thyroid cancer and other stroma-rich tumors.

Does the Use of Probe-based Near-infrared Autofluorescence Parathyroid Detection Benefit Parathyroidectomy?: A Randomized Single-center Clinical Trial.

OBJECTIVE: To evaluate the benefits of probe-based near-infrared autofluorescence (NIRAF) parathyroid identification during parathyroidectomy. BACKGROUND: Intraoperative parathyroid gland identification during parathyroidectomy can be challenging, while additionally requiring costly frozen sections. Earlier studies have established NIRAF detection as a reliable intraoperative adjunct for parathyroid identification. METHODS: Patients undergoing parathyroidectomy for primary hyperparathyroidism were prospectively enrolled by a senior surgeon (>20 years experience) and a junior surgeon (<5 years experience), while being randomly allocated to the probe-based NIRAF or control group. Data collected included procedure type, number of parathyroids identified with high confidence by the surgeon and the resident, number of frozen sections performed, parathyroidectomy duration, and number of patients with persistent disease at the first postoperative visit. RESULTS: One hundred sixty patients were randomly enrolled under both surgeons to the probe group (n=80) versus control (n=80). In the probe group, parathyroid identification rate of the senior surgeon improved significantly from 3.2 to 3.6 parathyroids per patient ( P <0.001), while that of the junior surgeon also rose significantly from 2.2 to 2.5 parathyroids per patient ( P =0.001). Parathyroid identification was even more prominent for residents increasing significantly from 0.9 to 2.9 parathyroids per patient ( P <0.001). Furthermore, there was a significant reduction in frozen sections utilized in the probe group versus control (17 vs 47, P =0.005). CONCLUSION: Probe-based NIRAF detection can be a valuable intraoperative adjunct and educational tool for improving confidence in parathyroid gland identification, while potentially reducing the number of frozen sections required.

Label-free intraoperative nerve detection and visualization using ratiometric diffuse reflectance spectroscopy.

Iatrogenic nerve injuries contribute significantly to postoperative morbidity across various surgical disciplines and occur in approximately 500,000 cases annually in the US alone. Currently, there are no clinically adopted means to intraoperatively visualize nerves beyond the surgeon's visual assessment. Here, we report a label-free method for nerve detection using diffuse reflectance spectroscopy (DRS). Starting with an in vivo rat model, fiber- and imaging-based DRS independently identified similar wavelengths that provided optimal contrast for nerve identification with an accuracy of 92%. Optical property measurements of rat and human cadaver tissues verify that the source of contrast between nerve and surrounding tissues is largely due to higher scattering in nerve and differences in oxygenated hemoglobin content. Clinical feasibility was demonstrated in patients undergoing thyroidectomies using both probe-based and imaging-based approaches where the nerve were identified with 91% accuracy. Based on our preliminary results, DRS has the potential to both provide surgeons with a label-free, intraoperative means of nerve visualization and reduce the incidence of iatrogenic nerve injuries along with its detrimental complications.

Adoption of Robotic Adrenalectomy: A Two-Institution Study of Surgeon Learning Curve.

BACKGROUND: Robotic adrenalectomy is feasible and safe, yet concerns over increased operative times and the learning curve (LC) for proficiency have limited its adoption. This study aimed to assess the LC for robotic adrenalectomy. METHODS: This is a two-institution retrospective review of consecutive unilateral minimally invasive adrenalectomies performed by four high-volume adrenal surgeons between 2007 and 2022. Two surgeons transitioned from laparoscopic to robotic adrenalectomy, and two surgeons adopted the approach, with proctoring, after completion of fellowship training without robotic experience. Operative time and complications were analyzed. Multivariable regression was used to identify factors associated with operative time. The number of cases required to overcome the LC was determined using the LC-cumulative-sum (LC-CUSUM) analysis. RESULTS: Of 457 adrenalectomies, 182 (40%) were laparoscopic and 275 (60%) robotic. The robotic approach was associated with shorter median operative time (106 vs 119 min; p = 0.002), fewer complications (6% vs 13%; p = 0.018), and fewer conversions to open adrenalectomy (1% vs 4%; p = 0.030), with no difference between the senior and junior surgeons. On adjusted analysis, factors associated with increased operative time were male sex (p < 0.001), BMI > 30 kg/m2 (p < 0.001), and higher gland weight (p < 0.001). The LC-CUSUM analysis showed proficiency after 8-29 procedures. Compared with the first 10 cases, there was a mean reduction in operative time of 14 min after 10-20 cases, 28 min after 20-30 cases, and 29 min after > 30 cases, regardless of surgeon experience. DISCUSSION: With dedicated teams and proctoring, robotic adrenalectomy can be safely adopted at high-volume centers with a minimal LC.

Adrenal Metastasectomy in the Era of Immuno- and Targeted Therapy.

Adrenal metastasectomy has an increasing role in multimodality oncologic care for diverse primary cancer types. In this review, we discuss the epidemiology, evaluation, and contemporary best practices in the management of adrenal metastases from various primaries. Initial evaluation of suspected adrenal metastases should include diagnostic imaging to assess the extent of tumor involvement and determine surgical resectability, as well as biochemical evaluation for hormone secretion. Biopsy has a minimal role and should only be performed in tumors that are established to be non-hormone secreting and when the biopsy results would change clinical management. Adrenal metastasectomy is associated with survival benefit in selected patients. We suggest that adrenal metastasectomy has the greatest benefit in four clinical scenarios: (1) disease limited to the adrenal gland in which adrenalectomy renders the patient disease-free; (2) isolated progression in the adrenal gland in the setting of otherwise controlled metastatic extra-adrenal disease; (3) need for palliation of symptoms related to adrenal metastases; or (4) in the context of tissue-based clinical trials. Both minimally invasive and open adrenalectomy techniques are safe and appear to have equivalent oncologic outcomes. Minimally invasive approaches are favored when technically feasible while maintaining oncologic principles. A multidisciplinary evaluation including clinicians with expertise in the primary cancer type is essential to the successful management of adrenal metastases.

Ultrasound Follow-Up of Benign Thyroid Nodules: A Scoping Review.

Background: For cytologically benign thyroid nodules with very low to intermediate suspicion ultrasound patterns, optimal ultrasound follow-up intervals and outcomes of discontinuing follow-up are unclear. Methods: Ovid MEDLINE, Embase, and Cochrane Central were searched through August 2022 for studies comparing different ultrasound follow-up intervals and discontinuation versus continuation of ultrasound follow-up. The population was patients with cytologically benign thyroid nodules and very low to intermediate suspicion ultrasound patterns, and the primary outcome was missed thyroid cancers. Utilizing a scoping approach, we also included studies that were not restricted to very low to intermediate suspicion ultrasound patterns or evaluated additional outcomes such as thyroid cancer-related mortality rate, nodule growth, and subsequent procedures. Quality assessment was performed, and evidence was synthesized qualitatively. Results: One retrospective cohort study (n = 1254; 1819 nodules) compared different first follow-up ultrasound intervals for cytologically benign thyroid nodules. There was no difference between >4- versus 1- to 2-year intervals to first follow-up ultrasound in the likelihood of malignancy (0.4% [1/223] vs. 0.3% [2/715]), and no cancer-related deaths occurred. Follow-up ultrasound at >4 years was associated with increased likelihood of ≥50% nodule growth (35.0% [78/223] vs. 15.1% [108/715]), repeat fine needle aspiration (19.3% [43/223] vs. 5.6% [40/715]), and thyroidectomy (4.0% [9/223] vs. 0.8% [6/715]). The study did not describe ultrasound patterns or control for confounders, and analyses were based on interval to first follow-up ultrasound only. Other methodological limitations were not controlling for variability in follow-up duration and unclear attrition. The certainty of evidence was very low. No study compared discontinuation of ultrasound follow-up versus continuation. Conclusions: This scoping review found that evidence comparing different ultrasound follow-up intervals in patients with benign thyroid nodules is limited to one observational study, but suggests that the subsequent development of thyroid malignancies is very uncommon regardless of follow-up interval. Longer follow-up may be associated with more repeat biopsies and thyroidectomies, which could be related to more interval nodule growth that meets thresholds for further evaluation. Research is needed to clarify optimal ultrasound follow-up intervals for low to intermediate suspicion cytologically benign thyroid nodules and outcomes of discontinuing ultrasound follow-up for very low suspicion nodules.

Emerging Imaging Technologies for Parathyroid Gland Identification and Vascular Assessment in Thyroid Surgery: A Review From the American Head and Neck Society Endocrine Surgery Section.

Importance: Identification and preservation of parathyroid glands (PGs) remain challenging despite advances in surgical techniques. Considerable morbidity and even mortality result from hypoparathyroidism caused by devascularization or inadvertent removal of PGs. Emerging imaging technologies hold promise to improve identification and preservation of PGs during thyroid surgery. Observation: This narrative review (1) comprehensively reviews PG identification and vascular assessment using near-infrared autofluorescence (NIRAF)-both label free and in combination with indocyanine green-based on a comprehensive literature review and (2) offers a manual for possible implementation these emerging technologies in thyroid surgery. Conclusions and Relevance: Emerging technologies hold promise to improve PG identification and preservation during thyroidectomy. Future research should address variables affecting the degree of fluorescence in NIRAF, standardization of signal quantification, definitions and standardization of parameters of indocyanine green injection that correlate with postoperative PG function, the financial effect of these emerging technologies on near-term and longer-term costs, the adoption learning curve and effect on surgical training, and long-term outcomes of key quality metrics in adequately powered randomized clinical trials evaluating PG preservation.

The use of an educational time-out in thyroid and parathyroid surgery to move the needle in periprocedural education.

BACKGROUND: As surgical training shifts toward a competency-based paradigm, deliberate practice for procedures must be a point of focus. The purpose of this study was to assess the impact of an educational time-out intervention on educational experience and operative performance in endocrine surgery. METHODS: For 12 months, third-year general surgery residents used the educational time-out to establish an operative step of focus for thyroidectomy and parathyroidectomy procedures. Data were collected using the System for Improving and Measuring Procedural Learning application and post-rotation surveys. The Zwisch scale was used to classify supervision, with meaningful autonomy defined as passive help or supervision only. RESULTS: Eight residents and 3 attending surgeons performed the educational time-out for a total of 211 operations (93% completion rate). At the end of each rotation, there was improvement in the frequency of goal setting. There was strong agreement (90%) that the intervention strengthened the educational experience. For most cases (52%), the residents were rated at active help. Residents performed a median of 3/6 thyroidectomy steps at meaningful autonomy and a median of 2/5 parathyroidectomy steps at meaningful autonomy. Review of the qualitative data revealed that optimal feedback was provided in 46% of cases. CONCLUSION: The educational time-out strengthened educational experiences. Stepwise procedural data revealed the varying levels of supervision that exist within an operation. Broader implementation of this intervention could facilitate competency-based procedural education.

Engineering functional 3-dimensional patient-derived endocrine organoids for broad multiplatform applications.

BACKGROUND: Recent advancements in 3-dimensional patient-derived organoid models have revolutionized the field of cancer biology. There is an urgent need for development of endocrine tumor organoid models for medullary thyroid carcinoma, adrenocortical carcinoma, papillary thyroid carcinoma, and a spectrum of benign hyperfunctioning parathyroid and adrenal neoplasms. We aimed to engineer functionally intact 3-dimensional endocrine patient-derived organoids to expand the in vitro and translational applications for the advancement of endocrine research. METHODS: Using our recently developed fine needle aspiration-based methodology, we established patient-derived 3-dimensional endocrine organoid models using prospectively collected human papillary thyroid carcinoma (n = 6), medullary thyroid carcinoma (n = 3), adrenocortical carcinoma (n = 3), and parathyroid (n = 5). and adrenal (n = 5) neoplasms. Multiplatform analyses of endocrine patient-derived organoids and applications in oncoimmunology, near-infrared autofluorescence, and radiosensitization studies under 3-dimensional in vitro conditions were performed. RESULTS: We have successfully modeled and analyzed the complex endocrine microenvironment for a spectrum of endocrine neoplasms in 3-dimensional culture. The endocrine patient-derived organoids recapitulated complex tumor microenvironment of endocrine neoplasms morphologically and functionally and maintained cytokine production and near-infrared autofluorescence properties. CONCLUSION: Our novel engineered endocrine patient-derived organoid models of thyroid, parathyroid and adrenal neoplasms represent an exciting and elegant alternative to current limited 2-dimensional systems and afford future broad multiplatform in vitro and translational applications, including in endocrine oncoimmunology.

Use of fluorescence imaging and indocyanine green during thyroid and parathyroid surgery: Results of an intercontinental, multidisciplinary Delphi survey.

BACKGROUND: In recent years, fluorescence imaging-relying both on parathyroid gland autofluorescence under near-infrared light and angiography using the fluorescent dye indocyanine green-has been used to reduce risk of iatrogenic parathyroid injury during thyroid and parathyroid resections, but no published guidelines exist regarding its use. In this study, orchestrated by the International Society for Fluorescence Guided Surgery, areas of consensus and nonconsensus were examined among international experts to facilitate future drafting of such guidelines. METHODS: A 2-round, online Delphi survey was conducted of 10 international experts in fluorescence imaging use during endocrine surgery, asking them to vote on 75 statements divided into 5 modules: 1 = patient preparation and contraindications to fluorescence imaging (n = 11 statements); 2 = technical logistics (n = 16); 3 = indications (n = 21); 4 = potential advantages and disadvantages of fluorescence imaging (n = 20); and 5 = training and research (n = 7). Several methodological steps were taken to minimize voter bias. RESULTS: Overall, parathyroid autofluorescence was considered better than indocyanine green angiography for localizing parathyroid glands, whereas indocyanine green angiography was deemed superior assessing parathyroid perfusion. Additional surgical scenarios where indocyanine green angiography was thought to facilitate surgery are (1) when >1 parathyroid gland requires resection; (2) during redo surgeries, (3) facilitating parathyroid autoimplantation; and (4) for the predissection visualization of abnormal glands. Both parathyroid autofluorescence and indocyanine green angiography can be used during the same procedure and employing the same imaging equipment. However, further research is needed to optimize the dose and timing of indocyanine green administration. CONCLUSION: Though further research remains necessary, using fluorescence imaging appears to have uses during thyroid and parathyroid surgery.

Intraoperative Ultrasound Guided Laparoscopic Spleen-Preserving Distal Pancreatectomy for Primitive Neuroendocrine Tumors in a Pediatric Patient With MEN-1.

This case details the presentation and surgical management of a 15-year-old male patient with multiple endocrine neoplasia syndrome type 1 (MEN1) who required distal pancreatectomy for multiple nonfunctional pancreatic tumors. An intraoperative ultrasound was utilized to allow for proper location of the distal pancreatectomy, as well as visualization of the splenic vessel relationships and to ensure all lesions were contained within the specimen. Pathology demonstrated 5 well-differentiated neuroendocrine tumors with no evidence of malignancy. This case utilized innovative technology and a multidisciplinary approach in a challenging case to achieve a safe minimally invasive resection. The use of ultrasound intraoperatively provided confidence that all lesions had been identified, as well as demonstration of safe planes separate from the nearby vasculature.

Survival After Adrenalectomy for Metastatic Lung Cancer.

BACKGROUND: Adrenal metastasectomy is associated with increased survival in non-small cell lung cancer (NSCLC) with isolated adrenal metastases. Although clinical use of adrenal metastasectomy has expanded, indications remain poorly defined. The aim of this study was to evaluate the clinical benefit of adrenal metastasectomy for all lung cancer subtypes. PATIENTS AND METHODS: We performed a retrospective cohort study of patients who underwent adrenal metastasectomy for metastatic lung cancer at six institutions between 2001 and 2015. The primary outcomes were disease-free survival (DFS) and overall survival (OS). Cox proportional hazards regressions and Kaplan-Meier survival analysis were performed. RESULTS: For 122 patients, the mean age was 60.5 years and 49.2% were female. Median time to detection of the metastasis was 11 months, and 41.8% were ipsilateral to the primary lung cancer. Median DFS was 40 months (1 year: 64.8%; 5 year: 42.9%). Factors associated with longer DFS included primary tumor resection [hazard ratio (HR): 0.001; p = 0.005], longer time to adrenal metastasis (HR: 0.94; p = 0.005), and ipsilateral metastases (HR: 0.13; p = 0.004). Shorter DFS corresponded with older age (HR: 1.11; p = 0.01), R1 resection (HR: 8.94; p = 0.01), adjuvant radiation (HR: 9.45; p = 0.02), and open adrenal metastasectomy (HR: 10.0; p = 0.03). Median OS was 47 months (1 year: 80.2%; 5 year: 35.2%). Longer OS was associated with ipsilateral metastasis (HR: 0.55; p = 0.02) and adjuvant chemotherapy (HR: 0.35; p = 0.02). Shorter OS was associated with extra-adrenal metastases at adrenalectomy (HR: 3.52; p = 0.007), small cell histology (HR: 15.0; p = 0.04), and lung radiation (HR: 3.37; p = 0.002). DISCUSSION: Durable survival was observed in patients undergoing adrenal metastasectomy and should be considered for isolated adrenal metastases of NSCLC. Small cell histology and extra-adrenal metastases are relative contraindications to adrenal metastasectomy.

ACR Appropriateness Criteria® Parathyroid Adenoma.

Hyperparathyroidism is defined as excessive parathyroid hormone production. The diagnosis is made through biochemical testing, in which imaging has no role. However, imaging is appropriate for preoperative parathyroid gland localization with the intent of surgical cure. Imaging is particularly useful in the setting of primary hyperparathyroidism whereby accurate localization of a single parathyroid adenoma can facilitate minimally invasive parathyroidectomy. Imaging can also be useful to localize ectopic or supernumerary parathyroid glands and detail anatomy, which may impact surgery. This document summarizes the literature and provides imaging recommendations for hyperparathyroidism including primary hyperparathyroidism, recurrent or persistent primary hyperparathyroidism after parathyroid surgery, secondary hyperparathyroidism, and tertiary hyperparathyroidism. Recommendations include ultrasound, CT neck without and with contrast, and nuclear medicine parathyroid scans. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Assessing Intraoperative Laser Speckle Contrast Imaging of Parathyroid Glands in Relation to Total Thyroidectomy Patient Outcomes.

Background: Accurate assessment of parathyroid gland vascularity is important during thyroidectomy to preserve the function of parathyroid glands and to prevent postoperative hypocalcemia. Laser speckle contrast imaging (LSCI) has been shown to be accurate in detecting differences in parathyroid vascularity. In this surgeon-blinded prognostic study, we evaluate the relationship between intraoperative LSCI measurements and postoperative outcomes of total thyroidectomy patients. Methods: Seventy-two thyroidectomy patients were included in this study. After thyroid resection, an LSCI device was used to image all parathyroid glands identified, and a speckle contrast value was calculated for each. An average value was calculated for each patient, and the data were grouped according to whether the patient had normal (16-77 pg/mL) or low levels of parathyroid hormone (PTH) measured on postoperative day 1 (POD1). The aim of this study was to establish a speckle contrast threshold for classifying a parathyroid gland as adequately perfused and to determine how many such glands are required for normal postoperative parathyroid function. Results: A speckle contrast limit of 0.186 separated the normoparathyroid and hypoparathyroid groups with 87.5% sensitivity and 84.4% specificity: 7 of 8 patients with low PTH on POD1 had an average parathyroid speckle contrast above this limit, while 54 of 64 patients with normal postoperative PTH had an average parathyroid speckle contrast below this limit. Taking this value as the threshold for adequate parathyroid perfusion, it was determined that only one vascularized gland was needed for normal postoperative parathyroid function: 64 of 69 patients (92.8%) with at least one vascularized gland (determined by LSCI) had normal postoperative PTH, while all 3 patients (100%) with no vascularized glands had low postoperative PTH. Overall, the rates of temporary and permanent hypoparathyroidism in this study were 8.3% and 1.4%, respectively. Conclusions: LSCI is a promising technique for assessing parathyroid gland vascularity. It has the potential to help reduce the incidence of hypocalcemia after thyroidectomy by providing surgeons with additional information during surgery to aid in the preservation of parathyroid function.