Background
Perineural invasion (PNI) is associated with aggressive tumor behavior, increased locoregional recurrence, and decreased survival in many carcinomas. However, the significance of PNI in ...papillary thyroid cancer (PTC) is incompletely characterized.
Methods
Patients diagnosed with PTC and PNI from 2010-2020 at a single, academic center were identified and matched using a 1:2 scheme to patients without PNI based on gross extrathyroidal extension (ETE), nodal metastasis, positive margins, and tumor size (±4 cm). Mixed and fixed effects models were used to analyze the association of PNI with extranodal extension (ENE)—a surrogate marker of poor prognosis.
Results
In total, 78 patients were included (26 with PNI, 52 without PNI). Both groups had similar demographics and ultrasound characteristics preoperatively. Central compartment lymph node dissection was performed in most patients (71%, n = 55), and 31% (n = 24) underwent a lateral neck dissection. Patients with PNI had higher rates of lymphovascular invasion (50.0% vs. 25.0%,
p
= 0.027), microscopic ETE (80.8% vs. 44.0%,
p
= 0.002), and a larger burden median 5 (interquartile range IQR 2-13) vs. 2 (1-5),
p
= 0.010 and size median 1.2 cm (IQR 0.6-2.6) vs. 0.4 (0.2-1.4),
p
= 0.008 of nodal metastasis. Among patients with nodal metastasis, those with PNI had an almost fivefold increase in ENE odds ratio OR 4.9 (95% confidence interval CI 1.5-16.5),
p
= 0.008 compared with those without PNI. More than a quarter (26%) of all patients had either persistent or recurrent disease over follow-up (IQR 16-54 months).
Conclusions
PNI is a rare, pathologic finding that is associated with ENE in a matched cohort. Additional investigation into PNI as a prognostic feature in PTC is warranted.
Although unilateral primary aldosteronism is the most common surgically correctable cause of hypertension, no standard criteria exist to classify surgical outcomes. We aimed to create consensus ...criteria for clinical and biochemical outcomes and follow-up of adrenalectomy for unilateral primary aldosteronism and apply these criteria to an international cohort to analyse the frequency of remission and identify preoperative determinants of successful outcome.
The Primary Aldosteronism Surgical Outcome (PASO) study was an international project to develop consensus criteria for outcomes and follow-up of adrenalectomy for unilateral primary aldosteronism. An international panel of 31 experts from 28 centres, including six endocrine surgeons, used the Delphi method to reach consensus. We then retrospectively analysed follow-up data from prospective cohorts for outcome assessment of patients diagnosed with unilateral primary aldosteronism by adrenal venous sampling who had undergone a total adrenalectomy, consecutively included from 12 referral centres in nine countries. On the basis of standardised criteria, we determined the proportions of patients achieving complete, partial, or absent clinical and biochemical success in accordance with the consensus. We then used logistic regression analyses to identify preoperative factors associated with clinical and biochemical outcomes.
Consensus was reached for criteria for six outcomes (complete, partial, and absent success of clinical and biochemical outcomes) based on blood pressure, use of antihypertensive drugs, plasma potassium and aldosterone concentrations, and plasma renin concentrations or activities. Consensus was also reached for two recommendations for the timing of follow-up assessment. For the international cohort analysis, we analysed clinical data from 705 patients recruited between 1994 and 2015, of whom 699 also had biochemical data. Complete clinical success was achieved in 259 (37%) of 705 patients, with a wide variance (range 17-62), and partial clinical success in an additional 334 (47%, range 35-66); complete biochemical success was seen in 656 (94%, 83-100) of 699 patients. Female patients had a higher likelihood of complete clinical success (odds ratio OR 2·25, 95% CI 1·40-3·62; p=0·001) and clinical benefit (complete plus partial clinical success; OR 2·89, 1·49-5·59; p=0·002) than male patients. Younger patients had a higher likelihood of complete clinical success (OR 0·95 per extra year, 0·93-0·98; p<0·001) and clinical benefit (OR 0·95 per extra year, 0·92-0·98; p=0·004). Higher levels of preoperative medication were associated with lower levels of complete clinical success (OR 0·80 per unit increase, 0·70-0·90; p<0·001).
These standardised outcome criteria are relevant for the assessment of the success of surgical treatment in individual patients and will allow the comparison of outcome data in future studies. The variable baseline clinical characteristics of our international cohort contributed to wide variation in clinical outcomes. Most patients derive clinical benefit from adrenalectomy, with younger patients and female patients more likely to have a favourable surgical outcome. Screening for primary aldosteronism should nonetheless be done in every individual fulfilling US Endocrine Society guideline criteria because biochemical success without clinical success is by itself clinically important and older women and men can also derive post-operative clinical benefit.
European Research Council; European Union's Horizon 2020; Else Kröner-Fresenius Stiftung; Netherlands Organisation for Health Research and Development-Medical Sciences; Japanese Ministry of Health, Labour and Welfare; Ministry of Health, Slovenia; US National Institutes of Health; and CONICYT-FONDECYT (Chile).
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.
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.
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.
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.
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 mm
2
vs 42.2 ± 17.8 mm
2
,
p
< 0.0001, pressure 29.5 ± 6.2 mmHg vs 33.9 ± 8.5 mmHg,
p
= 0.0009, DI 0.9 ± 0.4 mm
2
/mmHg vs 1.3 ± 0.6 mm
2
/mmHg,
p
= 0.001, and compliance 25.9 ± 12.8 mm
3
/mmHg vs 35.4 ± 13.4 mm
3
/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 mm
2
/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.
Background
The effectiveness of prophylactic central neck dissection (pCND) in the treatment of patients with papillary thyroid carcinoma (PTC) to prevent local recurrence is controversial. We ...performed a meta-analysis to assess the effect of pCND on local recurrence in PTC.
Methods
Exhaustive search of online search engines identified five retrospective studies that compared the local recurrence rates of PTC in patients without clinically detectable nodal disease in patients undergoing thyroidectomy + pCND (group A) to those undergoing thyroidectomy alone (group B). A meta-analysis was performed by the fixed effects method. Recurrence was documented by imaging, thyroglobulin detection, or reoperation. Location of recurrence was identified in either the central or lateral neck compartment.
Results
A total of 1264 patients were included, 396 in group A and 868 in group B. Follow-up ranged from 6 months to 27 years. The overall recurrence rate was 2.02% in group A versus 3.92% in group B (odds ratio OR = 1.05, 95% confidence interval 95% CI 0.48–2.31). The recurrence rate in the central neck compartment in group A was 1.86% compared to 1.68% in group B (OR = 1.31, 95% CI 0.44–3.91). The recurrence rate in the lateral neck compartment in group A was 3.73% compared to 3.79% in group B (OR = 1.21, 95% CI 0.52–2.75). There was no statistically significant difference in the OR in the local recurrence between the two groups.
Conclusions
This meta-analysis indicates that pCND does not greatly reduce local recurrence in thyroid cancer. However, the available studies have substantial limitations and a prospective multicenter study to determine the indications for pCND is warranted.
Risk assessment is critical to determine the timing of elective surgeries and preserve valuable resources in time of pandemic. This study was undertaken to better understand the potential value of ...molecular testing to risk‐stratify thyroid nodules with malignant cytology (Bethesda VI). Systematic review of the literature contributed 21 studies representing 2036 preoperative specimens. The BRAF p.V600E substitution was detected in 46% to 90% of cases with a pooled positivity rate of 70% (95% confidence intervals: 64%‐76%). None of the studies used comprehensive oncogene panels. Retrospective analysis of 531 clinical specimens evaluated with the next‐generation sequencing ThyGeNEXT Thyroid Oncogene Panel identified a total of 436 gene alterations. BRAF mutation rate was 64% in specimens tested as part of standard clinical care and 75% in specimens from cross‐sectional research studies (P = .022). Testing for additional actionable gene alterations such as TERT promoter mutations or RET and NTRK gene rearrangements further increased the diagnostic yield to 78%‐85% and up to 95% when including the ThyraMIR Thyroid miRNA Classifier. These data support the role of molecular cytopathology in surgical and therapeutic decision‐making and warrant additional studies.
Background
Vonoprazan is a new potassium-competitive acid blocker (P-CAB) that was recently approved by the FDA. It is associated with a fast onset of action and a longer acid inhibition time. ...Vonoprazan-containing therapy for helicobacter pylori eradication is highly effective and several studies have demonstrated that a vonoprazan-antibiotic regimen affects gut microbiota. However, the impact of vonoprazan alone on gut microbiota is still unclear.
Methods
We conducted a prospective randomized 12-week experimental trial with 18 Wistar rats. Rats were randomly assigned to one of 3 groups: (1) drinking water as negative control group, (2) oral vonoprazan (4 mg/kg) for 12 weeks, and (3) oral vonoprazan (4 mg/kg) for 4 weeks, followed by 8 weeks off vonoprazan. To investigate gut microbiota, we carried out a metagenomic shotgun sequencing of fecal samples at week 0 and week 12.
Results
For alpha diversity metrics at week 12, both long and short vonoprazan groups had lower Pielou’s evenness index than the control group (
p
= 0.019); however, observed operational taxonomic units (
p
= 0.332) and Shannon’s diversity index (
p
= 0.070) were not statistically different between groups. Beta diversity was significantly different in the three groups, using Bray–Curtis (
p
= 0.003) and Jaccard distances (
p
= 0.002). At week 12, differences in relative abundance were observed at all levels. At phylum level, short vonoprazan group had less of
Actinobacteria
(log fold change = − 1.88, adjusted
p
-value = 0.048) and
Verrucomicrobia
(lfc = − 1.76,
p
= 0.009).
At the genus level, long vonoprazan group had more
Bacteroidales
(lfc = 5.01,
p
= 0.021) and
Prevotella
(lfc = 7.79,
p
= 0.001). At family level, long vonoprazan group had more
Lactobacillaceae
(lfc = 0.97,
p
= 0.001),
Prevotellaceae
(lfc = 8.01,
p
< 0.001), and less
Erysipelotrichaceae
(lfc = − 2.9,
p
= 0.029).
Conclusion
This study provides evidence that vonoprazan impacts the gut microbiota and permits a precise delineation of the composition and relative abundance of the bacteria at all different taxonomic levels.
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.
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.
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).
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.
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