Minimally Invasive Thermal Ablation for Papillary Thyroid Microcarcinoma: Feasibility Analysis in Primary Healthcare Settings

ABSTRACTObjective:We aimed to evaluate the patients diagnosed with papillary thyroid carcinoma (PTC) and papillary thyroid microcarcinoma (PTMC) in terms of clinical, ultrasonographical (US) and histopathological features and their relationships with tumor size.Subjects and methods:We retrospectively evaluated 881 patients who underwent thyroid surgery in our clinic and diagnosed with PTC histopathologically were enrolled the study. Demographic characteristics, US findings and histopathological features were evaluated.Results:In total, 1264 nodules were identified in the 881 patients. The incidentality rates were higher in the PTMC group and also in the ≤ 5 mm group. In total multifocality rate was 32.9%, and was significantly higher in PTMC group than the PTC group. PTC and > 5 mm PTMC groups compared to PTMC and ≤ 5 mm groups respectively, were more aggresive histopathological features.Conclusions:Since the incidentality rates were found significantly more common in our patients with PTMC and those with ≤ 5 mm, ultrasonographic features of the nodules should be evaluated carefully and for cases which are suspicious with US, US-guided fine needle aspiration biopsy (FNAB) should be considered in order to make the correct treatment strategy. Also our study revealed that PTC and > 5 mm PTMC groups compared to PTMC and ≤ 5 mm groups respectively, have more aggresive histopathological features.

BackgroundOvertreatment of papillary thyroid microcarcinoma (PTMC) has become a common concern. This study aimed to compare clinicopathological features between PTMC and papillary thyroid carcinoma (PTC) and to explore whether surgery can confer significant survival benefits in all patients with PTC or PTMC.MethodsData of 145,951 patients with PTC registered in Surveillance, Epidemiology, and End Results (SEER) database and 8,751 patients with PTC in our institution were retrospectively collected. Patients with tumors less than 10 mm in diameter were classified as PTMC cohort and the rest as PTC cohort. Clinicopathological features between PTMC and PTC were compared on the basis of SEER cohort and validated with institutional data. Survival analysis was conducted to explore the effect of surgery on the prognosis of patients. To minimize potential confounders and selection bias, we performed propensity score matching (PSM) analysis to match more comparable cohorts.ResultsCompared with PTC, PTMC exhibited the following characteristics: more common in women and whites, older age at diagnosis, lower proportion of follicular variants, intraglandular dissemination, extraglandular and capsular invasion, higher proportion of multifocality, fewer lymph node and distant metastases, and higher cancer-specific survival (CSS) and overall survival (OS) (all p-value < 0.05). Regarding treatment, patients with PTMC received a lower proportion of radiotherapy, chemotherapy, and total thyroidectomy but a higher proportion of lobectomy and/or isthmectomy. There was no significant difference in CSS for patients with PTMC at stage T1N0M0 with or without surgery (P = 0.36).ConclusionGenerally, PTMC showed higher biological indolence than PTC, which meant a higher survival rate for patients in both OS and CSS. For patients with PTMC at staged T1N0M0, active surveillance (AS) may be a potentially feasible management strategy. However, the maintenance of good medical compliance and the management of psychological burden cannot be ignored for patients included in AS.

Objective: To study the clinical and pathologic factors of papillary thyroid microcarcinoma (PTMC) and its significance as a histopathologic subtype of papillary thyroid carcinoma (PTC). Methods: A retrospective study of 719 patients with non-high-risk PTMC who underwent surgery for the first time in the Peking University People's Hospital from January 2007 to June 2019 was conducted, the relationship between clinicopathologic factors and lymph node metastasis, and the expression of four tumor markers CK19, HMBE1, Galectin-3 and CD56 by immunohistochemistry were evaluated. Some comparisons were made with PTC. Results: The peak patients' age was 40-49 years for both non-high-risk PTMC and PTC; the lymph node metastasis rate was higher in the 30-39 years age group than the 50-59 years age group (P<0.05); the lymph nodes metastasis rate was significantly higher for multiple lesions than for single lesion (P<0.05). Lymph node metastasis rate of PTMC with capsular invasion was significantly higher than those without (P<0.05). There was no significant correlation between lymph node metastasis of PTMC and patients' gender, tumor location, tumor size, and lymphocytic thyroiditis. The expression rates of CK19, HMBE1 and Galectin-3 both in PTMC and PTC were 100%, and the expression rates of CD56 were 25.6% (85/332) and 20.0% (70/350) respectively. Conclusion: As the main pathologic subtype of PTC, a variety of clinicopathologic factors of PTMC are related to lymph node metastasis, and it is highly recommended to pay close attention to PTMC. The expression of tumor marker CD56 alone cannot be used as a basis to exclude PTMC and PTC.

The clinical significance of papillary thyroid microcarcinoma (PTMC) tumors < or =1 cm is widely debated. The objective of this study was to compare conventional papillary thyroid carcinoma (PTC) (tumors >1 cm) to PTMC and assess for differences in tumor characteristics and patient outcome. A retrospective chart review of patients with PTC or PTMC who were followed for a minimum of 3 years postoperatively and managed at a single academic institute was performed. Of 202 patients in the study, 66 (32.7%) had PTMC and 136 (67.3%) had conventional PTC. Patient and tumor characteristics including tumor multifocality, extrathyroidal extension, angiolymphatic invasion, and lymph node metastasis were similar between both groups. Twenty-one percent of the PTMC tumors were discovered incidentally. Patients with conventional PTC were significantly more likely to undergo treatment with radioactive iodine therapy compared to PTMC patients (86.4% vs. 66.7%, respectively, p < 0.003). Disease recurrence was observed in 40 patients and was not statistically different between the two groups; 11 (16.7%) in PTMC and 29 (21.3%) in conventional PTC, p = 0.57. Within the PTMC group, tumors of patients that recurred were significantly larger than those who remained disease free (8.1 mm vs. 6.4 mm, p < 0.05). None of the patients with incidental PTMC had disease recurrence. Angiolymphatic invasion was the only significant prognostic indicator of recurrence on multivariate analysis (p < 0.02). Nonincidental PTMC can have aggressive tumor features and disease recurrence similar to conventional PTC. These tumors should be managed like any other papillary thyroid malignancy.

Appropriate antibiotic use is a key strategy to control antibacterial resistance. The first step in achieving this is to identify the major problems in antibiotic prescription in health care facilities, especially in primary health care settings, which is where most patients receive medical care. To identify current patterns of antibiotic use and explore the reasons for inappropriate prescription in primary health care settings in China. A total of 48 primary health care facilities in China were randomly selected from 6 provinces at various levels of economic development. Data for the years 2009 through 2011 from 39 qualifying facilities (23 city and 16 rural primary health care centers) were analyzed retrospectively. The study sample consisted of prescription records for 7311 outpatient visits and 2888 inpatient hospitalizations. General health center information, drug usage, disease diagnoses, and antibiotic use by outpatients and inpatients were surveyed. Cases of inappropriate antibiotic prescription were identified. Most staff in the primary health care facilities had less than a college degree, and the medical staff consisted primarily of physician assistants, assistant pharmacists, nurses, and nursing assistants. The median (range) governmental contribution to each facility was 34.0% (3.6%-92.5%) of total revenue. The facilities prescribed a median (range) of 28 (8-111) types of antibiotics, including 34 (10-115) individual agents. Antibiotics were included in 52.9% of the outpatient visit prescription records: of these, only 39.4% were prescribed properly. Of the inpatients, 77.5% received antibiotic therapy: of these, only 24.6% were prescribed properly. Antibiotics were prescribed for 78.0% of colds and 93.5% of cases of acute bronchitis. Of the antibiotic prescriptions, 28.0% contained cephalosporins and 15.7% fluoroquinolones. A total of 55.0% of the antibiotic prescriptions were for antibiotic combination therapy with 2 or more agents. In nonsurgical inpatients in cities, the mean (SD) duration of antibiotic therapy was 10.1 (7.8) days. Of the surgical patients, 98.0% received antibiotics, with 63.8% of these prescriptions for prophylaxis. Antibiotics are frequently prescribed in Chinese primary health care facilities, and a large proportion of these prescriptions are inappropriate. Frequent and inappropriate use of antibiotics in primary health care settings in China is a serious problem that likely contributes to antimicrobial resistance worldwide.

The incidence of papillary thyroid carcinoma (PTC) has been rising annually, with papillary thyroid microcarcinoma (PTMC) accounting for more than half of the cases. While most PTMCs exhibit indolent growth and a favorable prognosis, some undergo clinical progression with poor outcomes. Thus, identifying biomarkers associated with PTC, particularly those related to PTMC progression, is crucial for precise risk stratification and treatment planning. This study utilized single-cell RNA sequencing on 19 surgical tissue specimens from 15 patients, including four para-tumor tissues, four non-progressive PTMCs, five progressive PTMCs, and six progressive PTCs. Key findings are corroborated through in vivo and in vitro experiments. Single-cell RNA sequencing and spatial transcriptomics characterized the cellular ecosystem within PTC, revealing multi-directional evolutionary patterns as PTMC progresses. Analysis of progression-specific alterations in intercellular communication networks highlighted the PROS1-MERTK signaling interaction as pivotal in PTMC progression. In vitro and in vivo models confirm that the PROS1-MERTK axis accelerates PTMC progression via paracrine and autocrine signaling. Furthermore, NFYB and FOXP2 are identified as activators of PROS1 transcription in fibroblasts, promoting PTMC progression through the MERTK/WNT/TGF-β signaling. These findings underscore the PROS1/MERTK axis as a critical component of the cellular microenvironment and a key regulatory mechanism in PTMC progression.

Objective:To explore the application value of high frequency ultrasound and ultrasound-guided fine needle aspiration biopsy（US-FNAB） in the diagnosis of papillary thyroid microcarcinoma（PTMC）, and to compare the characteristics and value of the two methods, so as to find a more convenient and non-invasive diagnostic method of PTMC, reduce unnecessary puncture and operation. Methods:The data of 190 postoperative pathologically confirmed PTMC patients admitted to Henan Province Cancer Hospital and Henan Provincial Hospital from January to June 2020 were retrospectively analyzed, with a total of 305 nodules, including 198 PTMC nodules and 107 benign thyroid nodules（BTN）. According to the postoperative pathological results, they were divided into groups, and the relationship between the ultrasound appearance of the nodules and whether the cervical lymph nodes could be explored and PTMC was analyzed by chi-square test and logistic regression, and its diagnostic value was evaluated. The Kappa consistency test was used to analyze the consistency between ultrasound, FNAB and surgical pathological diagnosis results. The accuracy, sensitivity and specificity of high-frequency ultrasound and US-FNAB were compared, and the ROC curve was used to calculate the maximum area under the curve to evaluate its effectiveness. Results:The chi-square test showed that there were statistically significant differences in the morphology, margin, internal echo, echo uniformity, calcification, aspect ratio, blood flow signal, and whether the cervical lymph nodes can be detected and other ultrasound signs between the PTMC group and the BTN group. Logistic regression analysis showed that irregular shape, unclear edges, internal hypoechoic, intranodular calcification are independent risk factors for PTMC. By consistency test, the consistency between high-frequency ultrasound, US-FNAB examination and surgical pathological diagnosis was good, Kappa value was 0.802 and 0.893（P<0.05）. Each nodule was examined by high-frequency ultrasound, and the diagnostic sensitivity, specificity, accuracy and AUC were 95.45%, 83.18%, 91.15% and 0.877 respectively. US-FNAB was performed on 189 of 305 thyroid nodules, and the diagnostic sensitivity, specificity, accuracy and AUC were 96.03%, 93.65%, 95.24% and 0.948 respectively. Conclusion:High frequency ultrasonic features such as internal hypoechoic, calcification in the nodules, unclear edges, and irregular morphology are of high value for the diagnosis of PTMC. Through data analysis, both high-frequency ultrasound and US-FNAB examination have high diagnostic value for PTMC. Compared with US-FNAB, high-frequency ultrasound has the advantages of low examination cost, non-invasive, simple operation and so on. For some patients with PTMC who do not have high risk factors, ultrasound can be used to actively monitor disease progression to avoid some unnecessary surgery.

There are multiple pathologic subtypes of papillary thyroid carcinoma (PTC), each with distinct clinical prognoses. However, the available data on the clinicopathologic risks associated with several common PTC subtypes are controversial and require more comprehensive evaluation. To address this, we conducted a systematic search of English-language databases, including PubMed, EMbase, Cochrane Library, and Web of Science, for studies on six PTC subtypes, including classic papillary thyroid carcinoma (CPTC), papillary thyroid microcarcinoma (PTMC), follicular variant of papillary thyroid carcinoma (FVPTC), tall cell variant of papillary thyroid carcinoma (TCVPTC), diffuse sclerosing variant of papillary thyroid carcinoma (DSVPTC), and columnar cell papillary thyroid carcinoma (CCVPTC). Our case-control study of clinicopathological prognostic analyses of six subtypes, with a search date of January 2000 to May 2024. Two researchers independently screened the literature, extracted data, and assessed quality and risk of bias according to set criteria. R software gemtc package, Stata 15.1 software were applied to perform reticulated Meta-analysis methods were applied to compare the clinicopathological features and prognostic assessment of classic papillary thyroid carcinoma and the other five subtypes in all the studies.The risk of distant metastasis was higher in patients with CCVPTC, TCVPTC, and DSVPTC than in CPTC.FVPTC and PTMC exhibit a lower risk of in situ tumor relapse compared to CPTC. The tumour size of TCVPTC was significantly larger than that of CPTC, while there was no significant difference in the tumour size of CCV, DSV, FVPTC, CPTC and PTMC. DSVPTC was significantly more multifocal than the other subtypes. This network meta-analysis confirms the aggressive biological behavior and poor prognosis associated with TCVPTC, DSVPTC, and CCVPTC. Therefore, these subtypes should be managed aggressively with total thyroidectomy and lymph node dissection if diagnosed preoperatively. In contrast, FVPTC and PTMC are less aggressive and have a better prognosis, suggesting that treatment and follow-up strategies for PTC should be tailored according to the histopathological subtype.

To compare the abilities of ultrasonography (US) and Computed Tomography (CT) to identify calcifications and to predict probability of malignancy for Papillary Thyroid Carcinoma (PTC) and Papillary Thyroid Microcarcinoma (PTMC). We reviewed 1008 cases of PTC/PTMC with calcifications reported by pre-operative US, CT, or post-operative pathology. The size of the thyroid nodule was obtained from the US report and the maximum diameter (d) was documented. According to the nodule size (d), the PTC and PTMC groups were each divided into two subgroups, as follows: large PTC group (d ≥ 2 cm), small PTC group (1 cm < d < 2 cm), large PTMC group (0.6 cm ≤ d ≤ 1 cm), and small PTMC group (d < 0.6 cm). In the 1008 patients, the ratio of females to males was 2.29 and the mean age was 40.9 years (standard deviation: 11.7 years). Of the 1008 records, 92.8% were found to have calcifications according to the US report, while 50.4% showed calcifications according to the CT report. This difference between US and CT reports was statistically significant (p < 0.0005). The percentages of US reports showing calcifications were similar for all four PTC and PTMC subgroups (93.7%, 94.3%, 92.1%, and 85.1%, respectively; p = 0.052), while the percentages of CT reports showing calcifications were significantly different among the PTC and PTMC subgroups (62.3%, 52.2%, 45.4%, and 31.3%, respectively; p < 0.0005). As for the prediction of malignancy, US was superior to CT in all four subgroups (large PTC group: 97.1% vs. 54.1%, small PTC group: 94.8% vs. 42.9%, large PTMC group: 97.2% vs. 32.0%, small PTMC group: 95.5% vs. 14.9%; p < 0.0005 for all pairwise comparisons). No significant difference was observed in terms of the ability of US to predict the malignancy of PTC versus PTMC (p = 0.31), while CT showed significant superiority in diagnosing PTC versus PTMC (p < 0.0005). The predictive value of CT for PTC declined as the nodule size decreased (p < 0.05 for all pairwise comparisons). Our results showed that US detected calcifications and predicted the malignancy of all nodule sizes of thyroid papillary carcinoma equally well, while the performance of CT declined with the reduction of nodule size.

As the high-pace development of sonography in recent years, the incidence of papillary thyroid carcinoma (PTC) has increased sharply worldwide, especially papillary thyroid microcarcinoma (PTMC). As we all know, PTMC is an indolent tumor, and level I lymph nodes (LNs) at a higher region relatively, so the majority of PTMCs admitted to surgery before the level I LNs metastasis. It is rare to see PTMC with level I LNs metastasis. At best of our known, there is only one Chinese research mentioned it but without a description of it. In this case, we reported a 30-year-old female who developed a recurrent submental cystic mass after being received treatment to remove a certain volume of light-yellow fluid. Pathology verified that mass in the submental area involved by PTMC. We consider that it may relate to age, multifocality, the diameter of PTMC, numbers of central compartment LNs, and "re-metastasis".

PurposeOur purposes were: 1) to estimate the prediction performance (PP) of cytology in identifying papillary thyroid carcinoma (PTC) subtypes; 2) to explore how the PTC subtypes distribute among the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) categories.MethodsNodules were included if both the histology with the PTC subtype report and the cytology report with the possible PTC subtype were available. The PP was calculated by making the proportion of True positives/False positives+false negatives.Results309 cytologically “suspicious for malignancy” and “malignant” thyroid nodules with PTC histology were evaluated. ACR TI-RADS categorization for classical PTC was significantly different from non-classical PTC (p-value 0.02). For the whole cohort the PP of cytologically classical cases was 0.74, while that of cytologically non classical cases was 0.41. ACR TI-RADS categorization was not significantly different for aggressive vs non-aggressive PTC subtypes (p-value 0.1). When considering only aggressive or non-aggressive PTC subtypes, the PP of cytologically classical cases was respectively 0.86 and 0.87, while that of cytologically non classical cases was respectively 0.27 and 0.22. The PP of cytologically classical cases was 0.73 and 0.79, respectively for macroPTCs and microPTCs, while that of cytologically non classical cases was 0.55 and 0.33, respectively for macroPTCs and microPTCs.ConclusionCytology examination reliably performed in predicting classical PTC versus non classical PTC subtypes. ACR TI-RADS categorization was significantly different among classical PTC versus non classical PTC subtypes.

Molecular Rearrangements and Morphology in Thyroid Cancer

Objective: To investigate the difference of prognostic factors and recurrence rates between papillary thyroid microcarcinoma (PTMC) and lager papillary thyroid carcinoma (PTC) and analyze the clinical pathological characteristics of PTMC suitable for surgery. Methods: A retrospective analysis on the clinicopathological features, expression level of of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E gene mutation and pigment epithelium-derived factor (PEDF), and postoperative follow-up results of the 251 PTC patients who underwent surgical treatment from October 2011 to October 2013, including 169 cases with PTMC and 82 with lager PTC (Tumor diameter>1 cm). Results: The BRAF V600E mutation rates of PTMC and lager PTC patients are 65.1%(110/169)and 78.0% (64/82) respectively, and the difference is statistically significant (P<0.05). The prevalence of extrathyroidal invasion (7.1%) and lymph nodes metastasis (27.2%) of the patients with PTMC were significantly lower than those of the patients with larger PTC (15.9% and 46.3%, respectively)(P<0.01). The follow-up durations for PTMC and lager PTC were (45.6±3.6) months and (45.0±3.4) months, respectively (P>0.05). There was no statistic significance for the difference in age, gender, coexistent hashimoto's thyroiditis, PEDF expression, and recurrence rate between the patients with PTMC and with larger PTC (P>0.05). The recurrence rate of the patients who have the high risk factors of PTMC was 1.6%(2/122)and that of larger PTC was 4.9% (4/82). Conclusions: Extrathyroid invasion, lymph node metastases and BRAF V600E gene mutation are the high risk factors of recurrent PTMC. The same treatment strategy should be considered for PTMC with coexistent high risk factors as that for larger PTC. For PTMC with BRAF V600E gene mutation, earlier surgical treatment is suggested. PTMC patients with BRAF V600E gene mutation and high cell subtype are suggested to undergo total thyroidectomy for the first operation in order to reduce the potential risk of recurrence.

When surgeons decide to perform lobectomy as the treatment of papillary thyroid carcinomas (PTCs), they must consider the possibility of contralateral cancer. We wanted to determine the incidence of bilateral PTCs (bPTCs) and analyze their characteristics. We also wanted to determine how many patients with bPTC were missed preoperatively. From January 2007 to May 2011, a total of 466 patients with PTC who were treated by total thyroidectomy at a single institution were enrolled. Patients were divided into two groups based on bilaterality. The patients with bPTCs were further investigated regarding the preoperative presence of the contralateral tumor. Bilaterality was seen in 29.8 % of PTC patients. In all, 36.8 % of PTCs ≥ 1 cm, and 25.7 % were papillary thyroid microcarcinomas (PTMCs). The presence of PTC in the contralateral lobe was missed in 15.8 % of bPTCs and in 21.3 % of bPTMCs. The rates of preoperatively nondetected contralateral cancer were 4.7 and 5.5 % for PTCs and PTMCs, respectively. Tumor size and multifocality were factors associated with bilaterality (p = 0.014 and p < 0.001, respectively). Bilaterality is found more frequently when the tumor is large. Multifocality also can help predict the possibility of bilaterality. Therefore, total thyroidectomy may be necessary for patients with a multifocal or large tumor. It should be noted that the presence of a contralateral cancer is missed in 4.7 and 5.5 % of patients with preoperatively diagnosed unilateral PTC and PTMC, respectively.

It has been broadly demonstrated that there has been a dramatic, worldwide, increase in the incidence of papillary thyroid carcinoma (PTC). Leenhardt et al. [2004] showed that there was approximately a 10-fold increase in the ratio of thyroid cancer for the cohort born in 1978 compared to those born in 1928. Davies & Welch [2006] found that the incidence of thyroid cancer in the United States had more than doubled from 1973 to 2002 and that this augmentation was virtually entirely due to an increase in PTC. However, it is uncertain whether this increase is a real phenomenon, or whether it is simply due to an increased rate of detection. Practices for management of thyroid diseases were deeply modified over the past few decades. The wide availability of ultrasonography (US) and fine needle aspiration biopsy (FNAB), as well as the improved accuracy of histopathological examination of surgical samples (that is the thinness of the anatomical slice of the thyroid specimen) are indicated as causes of this so-called spreading of the epidemic [Grodski & Delbridge, 2008]. Furthermore, the characteristics of PTCs, especially its size at diagnosis, have changed over time.