DAXX is associated with early recurrence of pancreatic neuroendocrine tumors after R0 resection.

INTRODUCTION: ATRX, DAXX, MEN1, and PTEN mutations are proposed drivers of pancreatic neuroendocrine tumor tumorigenesis and independent prognostic factors for metastasis and mortality. However, their implications after R0 resection remain debated. Thus, we sought to identify genomic signatures of pancreatic neuroendocrine tumor disease-specific mortality and recurrence after surgery for curative intent. METHODS: Pancreatic neuroendocrine tumor patients who underwent whole exome sequencing with available survival data were identified using cBioPortal. Clinicopathologic variables, genomics, and outcomes were analyzed. RESULTS: Seventy patients who underwent R0 resection were identified. Forty-five of 70 patients were disease free at last follow-up, whereas 25 of 70 patients had disease-specific mortality or recurrent disease and therefore were categorized as part of the recurrent cohort. There were no significant differences in age (P = .245), sex (P = .201), or median follow-up (38.9 vs 33.7 months, P = .122) between groups. Clinicopathologically, the recurrent cohort had significantly greater tumor size (median 5.0 cm vs 3.2 cm, P = .012) and were more likely to have vascular invasion (88% vs 40%, P = .000), positive lymph nodes (68.0% vs 35.6%, P = .013), and metastatic disease (44% vs 4.4%, P < .000). For both cohorts, most tumors were well or moderately differentiated. Tumor mutation burden was greater in the recurrent cohort (median 0.77 vs 0.43 mutations/Mb, P = .004). DAXX mutations were more frequent in the recurrent cohort (36% vs 11%, P = .026) and in those with vascular invasion (51% vs 92%, P = .010). CONCLUSION: Our analysis demonstrated the prognostic significance of DAXX mutations after curative-intent surgery. Future studies investigating DAXX mutations as a biomarker for aggressive features to guide treatment are warranted.

Evaluating the clinical performance of an updated microRNA classifier in indeterminate and RAS-mutated thyroid nodule management: A multi-institutional study.

BACKGROUND: Integrating microRNA markers with next-generation sequencing panels may enhance risk assessment of cytologically indeterminate thyroid nodules. The ThyGeNEXT-ThyraMIRv1 multiplatform test version 1 demonstrated limited utility in risk-stratifying RAS-mutated indeterminate thyroid nodules. We sought to validate the updated ThyraMIRv2 platform in clinical practice. METHODS: ThyGeNEXT/ThyraMIRv2, a 3-tiered microRNA classifier, were evaluated using a previously studied multi-institutional cohort of Bethesda III/IV nodules, with positive results having risk of malignancy ≥10%. In addition, ThyraMIRv2's clinical utility in RAS-mutated indeterminate thyroid nodules was assessed. RESULTS: In 366 indeterminate thyroid nodules, ThyraMIRv2 platform yielded a 30.3% positive-call rate. ThyraMIRv2 platform + nodules had greater operative rates (63.9% vs 36.1%, P < .0001) and cancer/noninvasive follicular thyroid neoplasm with papillary-like nuclear features diagnosis (65.9% vs 25.0%, P < .0001) than ThyraMIRv2 platform nodules. Compared with multiplatform test version 1, ThyraMIRv2 platform's diagnostic testing parameters did not improve significantly. Among 68 RAS-mutated nodules, ThyraMIRv2 classified 36.8%, 55.9%, and 7.4% as positive, moderate, and negative, respectively. All moderate nodules had risk of malignancy ≥10% and were combined with the positive cohort. No significant differences existed in operative rate (81.0% vs 60.0%, P = .272) or cancer/noninvasive follicular thyroid neoplasm with papillary-like nuclear features diagnosis (47.6% vs 40.0%, P > .999) between RAS-mutated positive/moderate and negative groups. For RAS-mutated nodules, ThyraMIRv2 demonstrated improved sensitivity (93.8% vs 64.7, P = .003) and decreased specificity (4.5% vs 34.8%, P = .008) compared with ThyGeNEXT-ThyraMIRv1 multiplatform test version 1, with comparable negative predictive value (33.3% vs 40.0%, P = .731) and positive predictive value (58.8% vs 59.5%, P = .864). CONCLUSION: ThyraMIRv2 platform does not improve indeterminate thyroid nodule malignancy stratification compared to ThyGeNEXT-ThyraMIRv1 multiplatform test version 1. ThyraMIRv2 improves malignant RAS-mutated nodule detection but increases false positives. Future studies encompassing a larger cohort of RAS-mutated with surgical pathology results are warranted to better characterize the performance parameters of this classifier.

Comparative anatomic and symptomatic recurrence outcomes of diaphragmatic suture cruroplasty versus biosynthetic mesh reinforcement in robotic hiatal and paraesophageal hernia repair.

BACKGROUND: Hiatal and paraesophageal hernia (HH/PEH) recurrence is the most common cause of failure after gastroesophageal anti-reflux surgery. Crural reinforcement with mesh has been suggested to address this issue, but its efficacy remains debated. In this study, we aimed to determine the impact of biosynthetic mesh reinforcement compared to suture cruroplasty on anatomic and symptomatic hernia recurrence. METHOD: Data of patients who underwent robotic HH/PEH repair with suture cruroplasty with or without biosynthetic mesh reinforcement between January 2012 and April 2024 were retrospectively reviewed. Gastroesophageal reflux disease symptoms and anatomic hernia recurrence were assessed at short-term (3 months to 1 year) and longer-term (≥ 1 year) follow-up. Symptomatic hernia recurrence was defined as having both anatomic recurrence and symptoms. RESULTS: Out of the 503 patients in the study, 308 had undergone biosynthetic mesh repair, while 195 had suture-only repair. After the surgery, both groups demonstrated comparable improvements in symptoms. Short-term anatomic hernia recurrence rates were 11.8% and 15.6% for mesh and suture groups, respectively (p = 0.609), while longer-term rates were 24.7% and 44.9% (p = 0.015). The rates of symptomatic hernia recurrence in the same group were 8.8% and 14.6% in the short-term (p = 0.256), and 17.2% and 42.2% in longer-term follow-ups (p = 0.003). In the repair of medium and large-size hernias, mesh reinforcement resulted in a 50.0% relative risk reduction in anatomic hernia recurrences and a 59.2% reduction in symptomatic hernia recurrences at ≥ 1-year follow-up. CONCLUSION: After more than a year of follow-up, it has been found that using biosynthetic mesh for medium and large hiatal or paraesophageal hernia repair significantly reduces the likelihood of both anatomic and symptomatic recurrence compared to using only suture cruroplasty. These findings strongly support the use of biosynthetic mesh to manage larger hernias. However, further long-term multicenter randomized studies are needed to provide more conclusive evidence.

Disparities in postoperative adjuvant therapy utilization and factors impacting survival among anaplastic thyroid cancer patients.

BACKGROUND: Anaplastic thyroid cancer (ATC) is highly aggressive with a poor prognosis. Adjuvant systemic therapy and radiation post-surgery are endorsed by NCCN and ATA guidelines. Our study aimed to identify those at risk of forgoing postoperative adjuvant treatment and to determine survival predictors. METHODS: We used the National Cancer Database (NCDB) to identify ATC patients who underwent upfront thyroidectomy from 2010 to 2017, excluding those opting for palliative care. We compared demographics, characteristics, treatments, and outcomes between those who received adjuvant therapy and those who did not. Predictors of receiving adjuvant therapy were identified using logistic regression, while Cox regression identified survival factors. RESULTS: Of 563 patients, 160 received no adjuvant treatment, 82 received radiation only, 16 received systemic therapy only, and 305 received combination therapy. Notably, over 75 â€‹% of patients who did not receive adjuvant treatment had it excluded from their treatment plan, not due to refusal. Older age (OR 0.92) and non-white race/ethnicity (OR 0.33) were significant predictors of not receiving adjuvant therapy. Undergoing a total thyroidectomy, an R0 or R1 resection, and radiation or combination therapy were associated with better survival, while non-metropolitan location, primary tumor size >7.5 â€‹cm, and stage IVC disease were negative factors. CONCLUSION: Total thyroidectomy, R0/R1 resection, and adjuvant therapy reduce mortality in ATC patients. However, older patients and minorities are less likely to receive adjuvant therapy, underscoring disparities in treatment adherence.

Clinical outcomes of endoscopic balloon dilation for dysphagia after anti-gastroesophageal reflux surgery.

BACKGROUND: Dysphagia is a potential complication following anti-gastroesophageal reflux surgery (ARS), with challenging management. Endoscopic balloon dilation is recommended for patients with significant dysphagia from tight wraps or strictures. We aim to evaluate factors associated with the need for post-ARS dilation and the outcomes of balloon dilation. Additionally, we assessed the predictors of sustained clinical failure after dilation. METHODS: A retrospective analysis was conducted on patients who underwent robotic or laparoscopic ARS between January 2012 and April 2023. Patients were divided based on whether they received balloon dilation using a through-the-scope wire-guided dilator. Excluded were those with pre-existing achalasia, other dilation devices, or inadequate follow-up. RESULTS: Of 1002 patients, 69 underwent 94 postoperative dilations, and the remainder were controls. The dilation cohort was older (63.78 vs. 56.14 years, P = 0.032) and had more magnetic sphincter augmentations (MSA) (P = 0.004), a prior history of ARS (P = 0.039), and a higher rate of laparoscopic surgery (P = 0.009) compared to controls. Of all dilations, 54 (57.5%) patients reported immediate dysphagia improvement, and 39 (41.5%) had sustained improvement. Sixteen (23.2%) patients required reoperation, primarily for hiatal hernia recurrence or slipped wrap. Multivariable logistic regression showed that MSA (OR 0.04, 95% CI 0.01-0.46, P = 0.031) and requiring multiple dilations (OR 0.16, CI 0.03-0.68) predicted sustained dilation failure. CONCLUSIONS: Factors including older age, history of prior ARS, and MSA are correlated with higher post-ARS dilation rates. Although dilation improves symptoms in approximately half of patients initially, one-fourth may eventually require reoperation, mostly due to a slipped wrap or hernia recurrence. Thus, in cases of persistent dysphagia, consideration for surgical failure is important, and further imaging and workup are warranted. Patients who undergo MSA and those who have more than one dilation are more likely to experience dilation failure.

The impact of obesity on gastroesophageal reflux disease recurrence following re-operative anti-reflux surgery.

INTRODUCTION: Obese patients represent a large proportion of patients experiencing recurrent reflux and re-operations after initial anti-reflux surgery. However, there is a limited data describing the impact of obesity on GERD recurrence following re-operative procedures. METHODS: A review of patients who underwent re-operative anti-reflux surgery (Re-ARS) between 2012 and 2023. Peri-operative characteristics and post-operative Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL) scores were compared across the three BMI categories: (BMI < 25 kg/m2, 25 ≤ BMI > 30 kg/m2, and BMI ≥ 30 kg/m2) over 12 IQR (9-14.9) months follow-up. Impedance planimetry measurements were included when it was utilized intraoperatively. RESULTS: Of 718 patients who underwent robotic ARS, 84 patients (11.6%) underwent Re-ARS, of which 29.7% had a BMI < 25 kg/m2, 35.7% were ≤ 25 BMI < 30 kg/m2, and 34.5% had a BMI ≥ 30 kg/m2. The lower esophageal sphincter distensibility decreased similarly between groups with no differences in post-induction [3.2 ± 2 vs 4.5 ± 3.1 vs 3.9 ± 2.5 mm2/mmHg, p = 0.44] or post-fundoplication values [1 ± 0.6 vs 1.3 ± 0.7 vs 1.2 ± 0.6 mm2/mmHg, p = 0.46]. There was a significant improvement in GERD-HRQL scores postoperatively compared to preoperative levels across the three BMI classes (BMI < 25 kg/m2: pre 17 IQR (12-22), post 7.5 (1.5-15), p = 0.04 vs ≤ 25 BMI < 30 kg/m2: pre 26 IQR (10-34), post 8 IQR (0-17), p < 0.01 vs BMI ≥ 30 kg/m2: pre 44 IQR (26-51), post 5 IQR (3.5-14.5), p < 0.001) during 12 IQR (9-14.9) months follow-up. The rates of hiatal hernia recurrence on barium swallow [5.2 vs 15.7 vs 13.7%, p = 0.32] during 7 IQR (5.2-9.2) months follow-up, and endoscopy [13.3 vs 16.6 vs 7.1%, p = 0.74] during 11.8 (IQR 5.6-17.1) months follow-up period were also similar between groups. CONCLUSION: GERD-HRQL scores in obese patients are expected to improve similarly compared to non-obese patients. Indicating that Re-ARS may be appropriate for patients across a range of BMIs.

Determination of causes of post-operative dysphagia after anti-reflux surgery based on intra-operative planimetry.

INTRODUCTION: Dysphagia after anti-reflux surgery (ARS) is one of the most common indications for re-operative anti-reflux surgery and a leading cause of patient dissatisfaction. Unfortunately, the factors affecting its development are poorly understood. We investigated the correlation between pre-operative manometric and the intra-operative impedance planimetry (EndoFLIP™) measurements and development of post-operative dysphagia. METHODS: A review of patients who underwent index robotic ARS in our institution. Patients who underwent pre-operative manometry and intra-operative EndoFLIP™ were included in our study. Dysphagia was assessed pre-operatively and at 3-month after surgery. RESULTS: Fifty-five patients (26.9%) reported post-operative dysphagia, and 34 (16.6%) reported new or worsening dysphagia. On pre-operative manometry, patients with post-operative dysphagia had a lower distal contractile integral [868.7 (IQR 402.2-1447) mmHg s cm vs 1207 (IQR 612.1-2111) mmHg s cm, p = 0.006) and lower esophageal sphincter (LES) pressure [14.7 IQR (8.9-23.6) mmHg vs 20.7 IQR (10.2-32.6) mmHg, p = 0.01] compared to those without post-operative dysphagia. They were also found to have higher pre-operative cross-sectional surface area (CSA) [83 IQR (44.5-112) mm2 vs 66 IQR (42-93) mm2, p = 0.02], and distensibility index (DI) [4.2 IQR (2.2-5.5) mm2/mmHg vs 2.9 IQR (1.6-4.6) mm2/mmHg, p = 0.003] compared to patients without post-operative dysphagia. Additionally, the decrease in CSA [- 34 (- 18.5, - 74.5) mm2 vs - 26.5 (- 10.5, - 53.7) mm2, p = 0.03] and DI [- 2.3 (- 1.2, - 3.7) mm2/mmHg vs - 1.6 (- 0.7, - 3.3) mm2/mmHg, p = 0.03] measurements were greater in patients with post-operative dysphagia. CONCLUSION: Patients who developed dysphagia post-operatively had poorer pre-operative motility and a greater change in LES characteristics intra-operatively. This finding suggests the utility of pre-operative manometry and intra-operative EndoFLIP in identifying patients at risk of developing dysphagia post-operatively.

Safety and efficacy of robotic anti-reflux surgery in geriatric patients: a comparative analysis.

INTRODUCTION: As our population ages, older adults are being considered for anti-reflux surgery (ARS). Geriatric patients typically have heightened surgical risk, and literature has shown mixed results regarding postoperative outcomes. We sought to evaluate the safety and efficacy of robotic ARS in the geriatric population. METHODS: We conducted a single-institution review of ARS procedures performed between 2009 and 2023. Patients ≥ 65 were assigned to the geriatric cohort. We compared operative details, lengths of stay (LOS), readmissions, reoperations, and complications between the two cohorts. The gastroesophageal reflux disease health-related quality of life (GERD-HRQL) survey and review of clinic notes were used to evaluate ARS efficacy. RESULTS: 628 patients were included, with 190 in the geriatric cohort. This cohort had a higher frequency of diabetes (16.3% vs 5.9% p < 0.0001), hypertension (50.0% vs 21.5% p < 0.0001), and heart disease (17.9% vs 2.3% p < 0.0001). Geriatric patients were more likely to exhibit hiatal hernias on imaging (51.6% vs 34.2% p < 0.0001) and were more likely to have large hernias (30.0% vs 7.1% p < 0.0001). Older adults were more likely to undergo Toupet fundoplications (58.4% vs 41.3%, p < 0.0001), Collis gastroplasties (9.5% vs 2.7% p < 0.0001), and relaxing incisions (11.6% vs 1.4% p < 0.0001). Operative time was longer for geriatric patients (132.0 min vs 104.5 min p < 0.0001). There were no significant differences in LOS, readmissions, or reoperations between cohorts. Geriatric patients exhibited lower rates of complications (7.4% vs. 14.6%, p = 0.011), but similar complication grades. Both groups had significant reduction in symptom scores from preoperative values. There were no significant differences in the reported symptoms between cohorts at any follow-up timepoint. CONCLUSION: Geriatric robotic ARS patients tend to do as well as younger adults regarding postoperative and symptomatic outcomes, despite presenting with larger hiatal hernias and shorter esophagi. Clinicians should be aware of possible need for lengthening procedures or relaxing incisions in this population.

Developing a predictive model for metastatic potential in pancreatic neuroendocrine tumor.

CONTEXT: Pancreatic neuroendocrine tumors (PNETs) exhibit a wide range of behavior from localized disease to aggressive metastasis. A comprehensive transcriptomic profile capable of differentiating between these phenotypes remains elusive. OBJECTIVE: Use machine learning to develop predictive models of PNET metastatic potential dependent upon transcriptomic signature. METHODS: RNA-sequencing data were analyzed from 95 surgically-resected primary PNETs in an international cohort. Two cohorts were generated with equally balanced metastatic PNET composition. Machine learning was used to create predictive models distinguishing between localized and metastatic tumors. Models were validated on an independent cohort of 29 formalin-fixed, paraffin-embedded samples using NanoString nCounter®, a clinically-available mRNA quantification platform. RESULTS: Gene expression analysis identified concordant differentially expressed genes between the two cohorts. Gene set enrichment analysis identified additional genes that contributed to enriched biologic pathways in metastatic PNETs. Expression values for these genes were combined with an additional 7 genes known to contribute to PNET oncogenesis and prognosis, including ARX and PDX1. Eight specific genes (AURKA, CDCA8, CPB2, MYT1L, NDC80, PAPPA2, SFMBT1, ZPLD1) were identified as sufficient to classify the metastatic status with high sensitivity (87.5% - 93.8%) and specificity (78.1% - 96.9%). These models remained predictive of the metastatic phenotype using NanoString nCounter® on the independent validation cohort, achieving a median AUROC of 0.886. CONCLUSIONS: We identified and validated an eight-gene panel predictive of the metastatic phenotype in PNETs, which can be detected using the clinically-available NanoString nCounter® system. This panel should be studied prospectively to determine its utility in guiding operative versus non-operative management.

Patterns in the Reporting of Aggressive Histologic Subtypes in Papillary Thyroid Cancer.

INTRODUCTION: The tall cell, columnar, and diffuse sclerosing subtypes are aggressive histologic subtypes of papillary thyroid cancer (PTC) with increasing incidence, yet there is a wide variation in reporting. We aimed to identify and compare factors associated with the reporting of these aggressive subtypes (aPTC) to classic PTC (cPTC) and secondarily identify differences in outcomes. METHODS: The National Cancer Database was utilized to identify cPTC and aPTC from 2004 to 2017. Patient and facility demographics and clinicopathologic variables were analyzed. Independent predictors of aPTC reporting were identified and a survival analysis was performed. RESULTS: The majority of aPTC (67%) were reported by academic facilities. Compared to academic facilities, all other facility types were 1.4-2.0 times less likely to report aPTC (P < 0.05). Regional variation in reporting was noted, with more cases reported in the Middle Atlantic, despite there being more total facilities in the South Atlantic and East North Central regions. Compared to the Middle Atlantic, all other regions were 1.4-5 times less likely to report aPTC (P < 0.001). Patient characteristics including race and income were not associated with aPTC reporting. Compared to cPTC, aPTC had higher rates of aggressive features and worse 5-y overall survival (90.5% versus 94.5%, log rank P < 0.001). CONCLUSIONS: Aggressive subtypes of PTC are associated with worse outcomes. Academic and other facilities in the Middle Atlantic were more likely to report aPTC. This suggests the need for further evaluation of environmental or geographic factors versus a need for increased awareness and more accurate diagnosis of these subtypes.

Radioactive iodine administration is not associated with improved disease-specific survival in classic papillary thyroid carcinoma greater than 4 cm confined to the thyroid.

BACKGROUND: We aimed to evaluate the impact of radioactive iodine on disease-specific survival in intrathyroidal (N0M0) papillary thyroid carcinoma >4 cm, given conflicting data in the American Thyroid Association guidelines regarding their management. METHODS: The Surveillance, Epidemiology, and End Results database was queried for N0M0 classic papillary thyroid carcinoma >4 cm. Kaplan-Meier estimates were performed to compare disease-specific survival between radioactive iodine-treated and untreated groups. A multivariable Cox regression was performed to identify predictors of disease-specific survival. RESULTS: There were more patients aged ≥55 (41.7% vs 32.3%, P = .001) and fewer multifocal tumors (25.3% vs 30.6%, P = .006) in the no radioactive iodine group. Ten-year disease-specific survival was similar between the radioactive iodine treated and untreated groups (97.2% vs 95.6%, P = .34). Radioactive iodine was not associated with a significant disease-specific survival benefit (adjusted hazard ratio = 0.78, confidence interval [0.39-1.58], P = .49). Age ≥55 (adjusted hazard ratio = 3.50, confidence interval [1.69-7.26], P = .001) and larger tumor size (adjusted hazard ratio = 1.04, confidence interval [1.02-1.06], P < .001) were associated with an increased risk of disease-specific death. Subgroup analyses did not demonstrate improved disease-specific survival with radioactive iodine in patients ≥55 and in tumors >5 cm. CONCLUSION: Adjuvant radioactive iodine administration in classic papillary thyroid carcinoma >4 cm confined to the thyroid did not significantly impact disease-specific survival. Thus, these patients may not require routine treatment with adjuvant radioactive iodine.

Low Mitotic Activity in Papillary Thyroid Cancer: A Marker for Aggressive Features and Recurrence.

CONTEXT: The significance of low mitotic activity in papillary thyroid cancer (PTC) is largely undefined. OBJECTIVE: We aimed to determine the behavioral landscape of PTC with low mitotic activity compared to that of no- and high-mitotic activity. METHODS: A single-institution consecutive series of PTC patients from 2018-2022 was reviewed. Mitotic activity was defined as no mitoses, low (1-2 mitoses/2 mm2) or high (≥3 mitoses/2 mm2) per the World Health Organization. The 2015 American Thyroid Association risk stratification was applied to the cohort, and clinicopathologic features were compared between groups. For patients with ≥6 months follow-up, Cox regression analyses for recurrence were performed. RESULTS: 640 PTCs were included - 515 (80.5%) no mitotic activity, 110 (17.2%) low mitotic activity, and 15 (2.3%) high mitotic activity. Overall, low mitotic activity exhibited rates of clinicopathologic features including vascular invasion, gross extrathyroidal extension, and lymph node metastases in between those of no- and high-mitotic activity. PTCs with low mitotic activity had higher rates of intermediate- and high-risk ATA risk stratification compared to those with no mitotic activity (p < 0.001). Low mitotic activity PTCs also had higher recurrence rates (15.5% vs. 4.5%, p < 0.001). Low mitotic activity was associated with recurrence, independent of the ATA risk stratification (HR 2.96; 95% CI 1.28-6.87, p = 0.01). CONCLUSIONS: Low mitotic activity is relatively common in PTC and its behavior lies within a spectrum between no- and high-mitotic activity. Given its association with aggressive clinicopathologic features and recurrence, low mitotic activity should be considered when risk stratifying PTC patients for recurrence.

Impedance planimetry (EndoFLIPTM) and surgical outcomes after Hill compared to Toupet fundoplication.

INTRODUCTION: Endoluminal functional lumen imaging probe (EndoFLIP) provides a real-time assessment of gastroesophageal junction (GEJ) compliance during fundoplication. Given the limited data on EndoFLIP measurements during the Hill procedure, we investigated the impact of the Hill procedure on GEJ compliance compared to Toupet fundoplication. METHODS: Patients who underwent robotic Hill or Toupet fundoplication with intraoperative EndoFLIP between 2017 and 2022 were included. EndoFLIP measurements of the GEJ included cross sectional surface area (CSA), intra-balloon pressure, high pressure zone length (HPZ), distensibility index (DI), and compliance. Subjective reflux symptoms, gastroesophageal reflux disease-health related quality of life (GERD-HRQL) score, and dysphagia score were assessed pre-operatively as well as at short- and longer-term follow-up. RESULTS: One-hundred and fifty-four patients (71.9%) had a Toupet fundoplication while sixty (28%) patients underwent the Hill procedure. The CSA [27.7 ± 10.9 mm2 vs 42.2 ± 17.8 mm2, p < 0.0001], pressure [29.5 ± 6.2 mmHg vs 33.9 ± 8.5 mmHg, p = 0.0009], DI [0.9 ± 0.4 mm2/mmHg vs 1.3 ± 0.6 mm2/mmHg, p = 0.001], and compliance [25.9 ± 12.8 mm3/mmHg vs 35.4 ± 13.4 mm3/mmHg, p = 0.01] were lower after the Hill procedure compared to Toupet. However, there was no difference in post-fundoplication HPZ between procedures [Hill: 2.9 ± 0.4 cm, Toupet: 3.1 ± 0.6 cm, p = 0.15]. Follow-up showed no significant differences in GERD-HRQL scores, overall dysphagia scores or atypical symptoms between groups (p > 0.05). CONCLUSION: The Hill procedure is as effective to the Toupet fundoplication in surgically treating gastroesophageal reflux disease (GERD) despite the lower CSA, DI, and compliance after the Hill procedure. Both procedures led to DI < 2 mm2/mmHg with no significant differences in dysphagia reporting (12-24) months after the procedure. Further studies to elucidate a cutoff value for DI for postoperative dysphagia development are still warranted.

Clinical utility of a microRNA classifier in cytologically indeterminate thyroid nodules with RAS mutations: A multi-institutional study.

BACKGROUND: Molecular testing guides the management of cytologically indeterminate thyroid nodules. We evaluated the real-world clinical benefit of a commercially available thyroid mutation panel plus microRNA risk classifier in classifying RAS-mutated nodules. METHODS: We performed a subgroup analysis of the results of molecular testing of Bethesda III/IV nodules using the ThyGenX/ThyGeNEXT-ThyraMIR platform at 3 tertiary-care centers between 2017 and 2021, defining a positive result as 10% or greater risk of malignancy. RESULTS: We identified 387 nodules from 375 patients (70.7% female, median age 59.3 years) who underwent testing. Positive nodules (32.3%) were associated with increased surgical intervention (74.4% vs 14.9%, P < .0001) and carcinoma on surgical pathology (46.4% vs 3.4%, P < .0001) compared to negative modules. RAS mutations were the most common mutations, identified in 71 of 380 (18.7%) nodules, and were classified as ThyraMIR- (28 of 71; 39.4%) or ThyraMIR+ (43 of 71; 60.6%). Among RAS-mutated nodules, there was no significant difference in operative rate (P = .2212) or carcinoma diagnosis (P = .6277) between the ThyraMIR+ and ThyraMIR- groups, and the sensitivity, specificity, negative predictive value, and positive predictive value of ThyraMIR were 64.7%, 34.8%, 40.0%, and 59.5%, respectively. CONCLUSION: Although testing positive is associated with malignancy in surgical pathology, the ThyraMIR classifier failed to differentiate between benign and malignant RAS-mutated nodules. Diagnostic lobectomy should be considered for RAS-mutated nodules, regardless of microRNA expression status.

How to Support a Surgeon Scientist: Lessons from National Institutes of Health K-Award Recipients.

BACKGROUND: Success in academic surgery is challenging and research cannot survive without funding. NIH K-awards are designed to mentor junior investigators to achieve independence. As a result we aimed to study K awardees in departments of surgery and learn from their experience. MATERIAL AND METHODS: Utilizing the NIH RePORTer database and filtering by department of surgery, clinically active surgeons receiving a K-award between 2008 and 2018 were asked to complete an online survey. Qualitative data from two open-ended questions were coded independently using standard qualitative methods by three researchers. Using grounded theory, major themes emerged from the codes. RESULTS: Of the 144 academic surgeons identified, 89 (62%) completed the survey. The average age was 39 ± 3 when the K-award was granted. Most identified as white (69%). Men (70%) were more likely to be married (P = 0.02) and have children (P = 0.05). To identify intention to pursue R01 funding, surgeons having a K-award for 5 y or more were analyzed (n = 45). Most either intended to (11%) or had already applied (80%) of which 36% were successful. Men were more likely to apply (P = 0.05). Major themes to succeed include protected time, mentorship, and support from leadership. Common barriers to overcome include balancing time, pressures to be clinically productive, and funding. CONCLUSIONS: The demographics and career trajectory of NIH K-awarded surgeons is described. The lack of underrepresented minorities receiving grants is concerning. Most recipients required more than one application attempt and plan to or have applied for R01 funding. The major themes were very similar; a supportive environment and time available for research are the most crucial factors to succeed as an academic surgeon.

PCP and SAX-3/Robo Pathways Cooperate to Regulate Convergent Extension-Based Nerve Cord Assembly in C. elegans.

Formation and resolution of multicellular rosettes can drive convergent extension (CE) type cell rearrangements during tissue morphogenesis. Rosette dynamics are regulated by both planar cell polarity (PCP)-dependent and -independent pathways. Here we show that CE is involved in ventral nerve cord (VNC) assembly in Caenorhabditis elegans. We show that a VANG-1/Van Gogh and PRKL-1/Prickle containing PCP pathway and a Slit-independent SAX-3/Robo pathway cooperate to regulate, via rosette intermediaries, the intercalation of post-mitotic neuronal cell bodies during VNC formation. We show that VANG-1 and SAX-3 are localized to contracting edges and rosette foci and act to specify edge contraction during rosette formation and to mediate timely rosette resolution. Simultaneous loss of both pathways severely curtails CE resulting in a shortened, anteriorly displaced distribution of VNC neurons at hatching. Our results establish rosette-based CE as an evolutionarily conserved mechanism of nerve cord morphogenesis and reveal a role for SAX-3/Robo in this process.