Diagnostic values of SurePath liquid-based cytology versus conventional smear in thyroid aspiration samples: A 13-year experience at a single institution.

BACKGROUND: Fine needle aspiration cytology (FNAC) is the most useful tool in the diagnosis of thyroid nodules. Liquid-based cytology (LBC) is replacing the conventional smear (CS) for evaluation of thyroid FNAC. In our institution, thyroid FNAC preparation was changed from CS to LBC SurePath in July 2016. This study aimed to compare the diagnostic value of SurePath with that of CS in thyroid lesions. METHODS: A total of 35,406 samples of thyroid FNAC (11,438 CS and 23,968 SurePath), collected from January 2010 to December 2022, were included in this study. We also examined the malignant rate using the surgical pathology diagnosis as the gold standard. RESULTS: The distribution of TBSRTC cytological categories was equivalent between CS and SurePath. The rate of nondiagnostic/unsatisfactory category was higher in CS compared to SurePath (43.4% vs. 22.3%; p < .05). After routine use of SurePath, the surgical resection rate was reduced from 12.0% to 8.6% (p < .05) and the malignant rate increased from 32.2% to 41.5% (p < .05). The sensitivities of CS and SurePath were 71.0% and 82.0%, respectively, and the specificities were 99.0% and 97.3%, respectively, whereas the positive predictive values were 97.8% and 96.8%, respectively, and the negative predictive values were 85.0% and 84.6%, respectively. Diagnostic accuracy of CS and SurePath were 88.5% and 89.7% respectively. CONCLUSION: SurePath can increase the sample adequacy, increase the sensitivity and reduce the workload and avoid unnecessary surgeries with similar accuracy to CS.

Judging robot ability: How people form implicit and explicit impressions of robot competence.

Robots' proliferation throughout society offers many opportunities and conveniences. However, our ability to effectively employ these machines relies heavily on our perceptions of their competence. In six studies (N = 2,660), participants played a competitive game with a robot to learn about its capabilities. After the learning experience, we measured explicit and implicit competence impressions to investigate how they reflected the learning experience. We observed two distinct dissociations between people's implicit and explicit competence impressions. Firstly, explicit impressions were uniquely sensitive to oddball behaviors. Implicit impressions only incorporated unexpected behaviors when they were moderately prevalent. Secondly, after forming a strong initial impression, explicit, but not implicit, impression updating demonstrated a positivity bias (i.e., an overvaluation of competence information). These findings suggest that the same learning experience with a robot is expressed differently at the implicit versus explicit level. We discuss implications from a social cognitive perspective, and how this work may inform emerging work on psychology toward robots. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Effectiveness of a Digital Decision Aid for Nutrition Support in Women with Gynaecological Cancer: A Comparative Study.

This study aimed to examine the effects of an animated Patient Decision Aid (PtDA) about dietary choices on decisional conflict and decision regret. A prospective, observational, two-group comparative effectiveness study was conducted with patients (n = 90) from a southern Taiwan oncology inpatient unit. Data included the Malnutrition Universal Screening Tool (MUST), laboratory results, 16-item Decisional Conflict Scale (sf-DCS), and 5-item Decision Regret Scale (DRSc). Data were collected at admission (T0), after the first-cycle of chemotherapy but before discharge (T1), and after the six-cycle chemotherapy protocol (T2) (around 3 months). Group A received standardized nutrition education and a printed brochure, while Group B watched a 10-minute information video during a one-on-one inpatient consultation and engaged in a values clarification exercise between T0 and T1. The percentage of women with a MUST score ≧1 in Group A sharply increased over time, but not in Group B. Decision aid usage significantly increased patients' hemoglobin and lymphocyte values over time (p < 0.05). The digital PtDA contributed to less decisional conflict and decision regret in at-risk patients and improved their nutritional well-being. Decision-aids help patients make healthcare decisions in line with their values, and are sustainable for use by busy clinicians.

Cytomorphological comparison of ThinPrep and SurePath liquid-based cytology in thyroid fine-needle aspiration.

BACKGROUND: The two widely established systems for liquid-based cytology (LBC), ThinPrep and SurePath, employ different principles. The aim of this study was to compare the cytomorphology of thyroid lesions prepared by the two techniques. METHODS: We retrospectively reviewed 44 thyroid FNA specimens prepared by LBC, including 20 ThinPrep and 22 SurePath. Cytologic diagnoses were made according to the Bethesda system and cytomorphologic parameters were evaluated. RESULTS: Acellular smears were significantly frequent in ThinPrep than SurePath (10% vs. 0%). Both techniques produced a clean background, well cell preservation, and not apparent cell shrinkage. ThinPrep showed significantly lower cellularity than SurePath (25% vs. 4.3%). ThinPrep produced considerable flattening and fragmented clusters, while SurePath contained larger clusters in a three-dimensional configuration. Colloid was significantly reduced in amount and fragmented in ThinPrep, and was easily observed in SurePath. In cases of Hashimoto's thyroiditis, ThinPrep produced much less leukocytes in background than SurePath. Aggregates of fibrin and leukocytes were frequently present in 10/16 cases (62.5%) processed by ThinPrep. Air-dry artifact at periphery of the ring was present in 6/16 cases (37.5%) processed by ThinPrep. The nuclear features of papillary carcinoma were similarly evident in both LBC preparations. CONCLUSION: SurePath seems to be superior to ThinPrep for diagnosing benign entities based on adequate representation of colloid and lymphocytes. The cell quality of both techniques in thyroid FNA was comparable, while each method introduces its own unique cytologic artifacts related to its methodology. We should recognize the cytomorphologic alterations to avoid misinterpretations.

Lymphocyte-Rich Hepatocellular Carcinoma with Multiple Lymphadenopathy and Positive Epstein-Barr Virus Encoding Region.

Lymphocyte-rich hepatocellular carcinoma (HCC) represents the rarest subtype among the various subgroups of HCC, and limited clinical data are available for this particular subtype. It is commonly observed as a solitary lesion and tends to present at an early stage. Histopathological examination typically reveals tumor cells infiltrated by a lymphocyte-rich background, leading to its designation as lymphoepithelioma-like HCC. Unlike other lymphoepithelioma-like tumors associated with the Epstein-Barr virus (EBV), lymphocyte-rich HCC is predominantly negative for EBV. This subtype is characterized by more favorable clinical outcomes and prognosis compared to conventional HCC. Here, we present a case of lymphocyte-rich hepatocellular carcinoma (HCC) characterized by the presence of bilateral hepatic tumors and concurrent multiple lymphadenopathy. Interestingly, contrary to previous literature, the examination for the Epstein-Barr virus (EBV) revealed a positive result in this particular case.

Ten-year follow-up of renal adenomatosis with magnetic resonance imaging: a case report.

BACKGROUND: Renal adenomatosis is a rare disease that presents as multiple papillary adenomas in the bilateral kidneys. Moreover, papillary adenoma is considered a precursor to papillary renal cell carcinoma. Therefore, patients with renal adenomatosis may have higher risk of developing malignancy than patients without this benign condition. CASE PRESENTATION: We present the case of a 62-year-old Asian woman with past history of papillary thyroid cancer. She underwent contrast-enhanced magnetic resonance imaging of the abdomen to screen for metastasis in 2010 and was followed up with computed tomography or magnetic resonance imaging annually. She was found to have a right renal tumor on computed tomography and underwent partial nephrectomy. The pathological diagnosis of the right renal tumor was angiomyolipoma. Renal adenomatosis was also histologically confirmed in the renal parenchyma adjacent to the angiomyolipoma. In this case report, we demonstrate the natural course of renal adenomatosis over 10 years using imaging studies. The benign tumors gradually progressed during the follow-up period. Larger tumor sizes and more hypoenhanced nodules in the bilateral kidneys were observed on follow-up computed tomography and magnetic resonance imaging. CONCLUSIONS: Due to its malignant potential, the clinical course of renal adenomatosis must be monitored. We present the natural course of renal adenomatosis with magnetic resonance imaging during a 10-year follow-up period.

Nasopharyngeal Radiation-Induced Sarcoma: A Case Report.

The primary treatment for nasopharyngeal carcinoma (NPC) is radiotherapy. In rare cases, patients with NPC treated with radiotherapy may develop radiation-induced sarcoma (RIS), a malignant tumor, in the field of previous radiation. The prognosis is poor, and complete surgical resection is the only potentially curative treatment. We report a case of radiation-induced nasopharyngeal sarcoma after radiotherapy for NPC with suspected lung and liver metastases in a 69-year-old woman.

Cost and Effectiveness of Long-Term Care Following Integrated Discharge Planning: A Prospective Cohort Study.

Little is known about the effects of seamless hospital discharge planning on long-term care (LTC) costs and effectiveness. This study evaluates the cost and effectiveness of the recently implemented policy from hospital to LTC between patients discharged under seamless transition and standard transition. A total of 49 elderly patients in the standard transition cohort and 119 in the seamless transition cohort were recruited from November 2016 to February 2018. Data collected from medical records included the Multimorbidity Frailty Index, Activities of Daily Living Scale, and Malnutrition Universal Screening Tool during hospitalization. Multiple linear regression and Cox regression models were used to explore risk factors for medical resource utilization and medical outcomes. After adjustment for effective predictors, the seamless cohort had lower direct medical costs, a shorter length of stay, a higher survival rate, and a lower unplanned readmission rate compared to the standard cohort. However, only mean total direct medical costs during hospitalization and 6 months after discharge were significantly (p < 0.001) lower in the seamless cohort (USD 6192) compared to the standard cohort (USD 8361). Additionally, the annual per-patient economic burden in the seamless cohort approximated USD 2.9-3.3 billion. Analysis of the economic burden of disability in the elderly population in Taiwan indicates that seamless transition planning can save approximately USD 3 billion in annual healthcare costs. Implementing this policy would achieve continuous improvement in LTC quality and reduce the financial burden of healthcare on the Taiwanese government.

Primary small cell neuroendocrine carcinoma in the nasal cavity: A CARE-compliant case report.

RATIONALE: Small cell neuroendocrine carcinoma of the nasal cavity and paranasal sinuses is a rare but aggressive neoplasm with a poor prognosis and a strong propensity for regional recurrence and distant metastasis. Diagnosis is challenging and relies on immunohistochemical study. Treatment includes surgical resection, radiation therapy, chemotherapy, or a combination of these modalities. However, the optimal therapeutic strategy is still controversial. Due to its rarity, the complexity of the histological diagnosis, and the variety of the treatment regimens, we presented a case of primary small cell neuroendocrine carcinoma in the nasal cavity with description of the clinical manifestation, pathology features, and our treatment regimen. PATIENT CONCERNS: An 82-year-old female patient with hypertension presented with right epistaxis on and off with nasal obstruction for several days. DIAGNOSIS: An exophytic mass over the posterior end of the right inferior turbinate was found on nasopharyngoscope. Biopsy was done and the pathology confirmed small cell carcinoma, strongly positive for cytokeratin (AE1/AE3) and insulinoma-associated protein 1 (INSM-1), scatteredly positive for chromogranin A, synaptophysin and CD56. The final diagnosis was small cell neuroendocrine carcinoma of right nasal cavity, pT1N0M0, stage I. INTERVENTIONS: The patient underwent wide excision of right intra-nasal tumor and post-operative radiotherapy with a dose of 6600 cGy in 33 fractions. OUTCOMES: No local recurrence or distant metastasis was noted during the 12 months of follow-up. LESSONS: Multimodality treatment remains the most common therapeutic strategy, although no proven algorithm has been established due to the rarity of this disease. Further investigation is needed for providing evidence to standardize the treatment protocol.

Prognostic Value of a Glycolytic Signature and Its Regulation by Y-Box-Binding Protein 1 in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer as it shows a high capacity for metastasis and poor prognoses. Metabolic reprogramming is one of the hallmarks of cancer, and aberrant glycolysis was reported to be upregulated in TNBC. Thus, identifying metabolic biomarkers for diagnoses and investigating cross-talk between glycolysis and invasiveness could potentially enable the development of therapeutics for patients with TNBC. In order to determine novel and reliable metabolic biomarkers for predicting clinical outcomes of TNBC, we analyzed transcriptome levels of glycolysis-related genes in various subtypes of breast cancer from public databases and identified a distinct glycolysis gene signature, which included ENO1, SLC2A6, LDHA, PFKP, PGAM1, and GPI, that was elevated and associated with poorer prognoses of TNBC patients. Notably, we found a transcription factor named Y-box-binding protein 1 (YBX1) to be strongly associated with this glycolysis gene signature, and it was overexpressed in TNBC. A mechanistic study further validated that YBX1 was upregulated in TNBC cell lines, and knockdown of YBX1 suppressed expression of those glycolytic genes. Moreover, YBX1 expression was positively associated with epithelial-to-mesenchymal transition (EMT) genes in breast cancer patients, and suppression of YBX1 downregulated expressions of EMT-related genes and tumor migration and invasion in MDA-MB-231 and BT549 TNBC cells. Our data revealed an YBX1-glycolysis-EMT network as an attractive diagnostic marker and metabolic target in TNBC patients.

Diagnostic Agreement for High-Grade Urothelial Cell Carcinoma in Atypical Urine Cytology: A Nationwide Survey Reveals a Tendency for Overestimation in Specimens with an N/C Ratio Approaching 0.5.

In the Paris System (TPS), standardized cytomorphological criteria and diagnostic categories were proposed for reporting urine cytology. To evaluate the diagnostic agreement and interobserver concordance for assessing TPS criteria, the Taiwan Society of Clinical Cytology organized an online survey with 10 atypical urine cytology cases. A total of 137 participants completed the survey. The mean agreement of diagnosis was 51.2%, ranging from 34.3% to 83.2% for each case. For 60% (6/10) of cases, the agreement was <50%. The interobserver concordance of diagnosis and cytological criteria assessment showed poor agreement. The nuclear-to-cytoplasmic (N/C) ratio had the highest kappa value of 0.386, indicating a significantly higher interobserver concordance and reproducibility than the other three TPS criteria. The correct rate of assessing the N/C ratio increased as the N/C ratio increased (correlation coefficient: 0.891, p < 0.01). Three cases with an N/C ratio near 0.5 were overestimated. Poor interobserver concordance of diagnosis and TPS criteria was revealed. Compared with other cytological features, the N/C ratio assessment was quantitative and more reproducible, but a tendency to overestimate cells was noted when the N/C ratio was approximately 0.5. Continuing education programs should emphasize the accurate assessment of N/C ratio to improve the application of TPS.

Time-Dependent Squamous Cell Carcinoma Antigen in Prediction of Relapse and Death of Patients With Cervical Cancer.

OBJECTIVE: The aim of the study was to develop a methodology to identify the best use of a longitudinally measured biomarker in relevance to prognosis. MATERIALS AND METHODS: Data of squamous cell carcinoma antigen (SCC-Ag) from 770 patients with cervical squamous cell carcinoma (SCC) were used. The pretreatment, nadir, and time-dependent SCC-Ag values were analyzed in relevance to disease relapse and death with univariate and multivariate analysis side by side with a variety of available clinicopathologic factors. The predictive power of the significant variates was evaluated by C-index with 5-fold cross validation. RESULTS: The pretreatment, nadir, and time-dependent SCC-Ag were all significant risk factors for both relapse and death in the univariate analysis (p < .05), and the time-dependent SCC-Ag had the highest C-index in both events. The nadir and time-dependent SCC-Ag were both independently significant in response to relapse with International Federation of Gynecology and Obstetrics (FIGO) stage as the covariate, and the latter had a higher C-index (0.745). Only the time-dependent SCC-Ag was independently significant together with FIGO stage in response to death with the C-index at 0.844. CONCLUSIONS: Increases in the serum level of SCC-Ag in cervical SCC patients suggest a higher risk of both relapse and death. The best use of serial SCC-Ag measurements is to include the time-dependent value in prognostic assessment with FIGO stage also accounted for. Cervical SCC patients should be followed up on their levels of SCC-Ag, and prognostic evaluation should be updated with recent measurements.

Metastatic Colorectal Cancer Rewrites Metabolic Program Through a Glut3-YAP-dependent Signaling Circuit.

Rationale: Cancer cells reprogram cellular metabolism to fulfill their needs for rapid growth and metastasis. However, the mechanism controlling this reprogramming is poorly understood. We searched for upregulated signaling in metastatic colorectal cancer and investigated the mechanism by which Glut3 promotes tumor metastasis. Methods: We compared RNA levels and glycolytic capacity in primary and metastatic colon cancer. The expression and association of Glut3 with clinical prognosis in colon cancer tissues was determined by immunohistochemistry. Glut3 gain-of-function and loss-of-function were established using colon cancer HCT116, HT29, and metastatic 116-LM cells, and tumor invasiveness and stemness properties were evaluated. Metabolomic profiles were analyzed by GC/MS and CE-TOF/MS. The metastatic burden in mice fed a high-fat sucrose diet was assessed by intravenous inoculation with Glut3 knockdown 116-LM cells. Results: Upregulation of glycolytic genes and glycolytic capacity was detected in metastatic colorectal cancer cells. Specifically, Glut3 overexpression was associated with metastasis and poor survival in colorectal cancer patients. Mechanistically, Glut3 promoted invasiveness and stemness in a Yes-associated protein (YAP)-dependent manner. Activation of YAP in turn transactivated Glut3 and regulated a group of glycolytic genes. Interestingly, the expression and phosphorylation of PKM2 were concomitantly upregulated in metastatic colorectal cancer, and it was found to interact with YAP and enhance the expression of Glut3. Importantly, a high-fat high-sucrose diet promoted tumor metastasis, whereas the inhibition of either Glut3 or YAP effectively reduced the metastatic burden. Conclusion: Activation of the Glut3-YAP signaling pathway acts as a master activator to reprogram cancer metabolism and thereby promotes metastasis. Our findings reveal the importance of metabolic reprogramming in supporting cancer metastasis as well as possible therapeutic targets.

Succinate Dehydrogenase-Deficient Renal Cell Carcinoma.

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma is a recently recognized distinct subtype of renal cell carcinoma in the 2016 World Health Organization classification. It is associated with SDH gene germline mutations, which also cause paraganglioma/pheochromocytoma, gastrointestinal stromal tumor, and pituitary adenoma. The tumor most commonly presents in young adulthood. The tumors are arranged in solid nests or in tubules and frequently show cystic change. The tumors are composed of cuboidal to oval cells with round nuclei, dispersed chromatin, and inconspicuous nucleoli. The cytoplasm is eosinophilic or flocculent but not truly oncocytic. The most distinctive histologic feature is the presence of cytoplasmic vacuoles or inclusions. Loss of SDH subunit B immunostaining is needed for a definite diagnosis. The prognosis is good for low-grade tumors but worse for tumors with high-grade nuclei, sarcomatoid change, or coagulative necrosis. Long-term follow-up is indicated.

The antipsychotic chlorpromazine suppresses YAP signaling, stemness properties, and drug resistance in breast cancer cells.

The major obstacle in current cancer therapy is the existence of cancer stem cells (CSCs), which are responsible for therapeutic resistance and contribute to metastasis and recurrence. Identification of reliable biomarkers for diagnostic and therapeutic targets is necessary for drug development and cancer treatment. In this study, we identified that the antipsychotic chlorpromazine (CPZ) exhibited potent anti-breast cancer and anti-CSC capabilities. Treatment with CPZ suppressed stemness properties including mammosphere formation, aldehyde dehydrogenase (ALDH) activity, and stemness-related gene expressions in breast cancer cells and CSCs. Moreover, CPZ increased the susceptibility of breast cancer MCF7 cells and drug-resistant MCF7/ADR cells when combined with chemotherapies. Mechanistically, we identified that CPZ suppressed yes-associated protein (YAP) through modulating Hippo signaling and promoting proteasomal degradation of YAP. Elevated expression of YAP was confirmed to be crucial for stemness-related gene expressions, and was associated with invasiveness and stem-like signatures in breast cancer patients. Moreover, overexpression of YAP conferred poor outcomes particularly of basal-like breast cancer patients. Our data showed that YAP is a promising therapeutic target for breast CSCs, and CPZ has the potential to be a repurposed drug for breast cancer treatment.

Activation of fibroblasts by nicotine promotes the epithelial-mesenchymal transition and motility of breast cancer cells.

The tumor microenvironment plays an important role in tumor initiation and progression. It is well documented that nicotine participates in cigarette smoking-related malignancies. Previous studies focused on the effects of nicotine on tumor cells; however, the role of the microenvironment in nicotine-mediated tumorigenesis is poorly understood. Herein, we investigated the effect and molecular mechanism of nicotine on fibroblasts and its contribution to breast cancer. We found that nicotine induced the epithelial-mesenchymal transition (EMT) of breast cancer cells and promoted activation of fibroblasts. Interestingly, conditioned medium from nicotine-activated fibroblasts (Nic-CM) had a greater impact on promoting the EMT and migratory capability toward cancer cells than did treatment with nicotine alone. Production of connective tissue growth factor (CTGF) and transforming growth factor (TGF)-ß by nicotine-treated fibroblasts was demonstrated to be crucial for promoting the EMT and cancer cell migration, and blocking of CTGF and TGF-ß in Nic-CM-suppressed tumor motility. Moreover, nicotine induced expressions of CTGF, and TGF-ß in fibroblasts as identified through α7 nicotinic acetylcholine receptor (nAChR)-dependent activation of the AKT/TAZ signaling mechanism. Together, our data showed for the first time that activation of fibroblasts is largely responsible for accelerating smoking-mediated breast cancer progression.

Podocalyxin-Like Protein 1 Regulates TAZ Signaling and Stemness Properties in Colon Cancer.

Colon cancer is the third most common cancer in the world and the second most common cause of cancer-related mortality. Molecular biomarkers for colon cancer have undergone vigorous discovery and validation. Recent studies reported that overexpression of podocalyxin-like protein 1 (PODXL) is associated with distant metastasis and poor prognosis across several types of malignancies. Its role and underlying molecular mechanism, however, are not yet fully understood. In the present study, we revealed that the Hippo transducer, the transcriptional coactivator with PDZ-binding motif (TAZ), acts as a downstream mediator of PODXL in colon cancer. Inhibition of PODXL resulted in the suppression of TAZ signaling and the downregulation of Hippo downstream genes. Moreover, PODXL plays a critical role in cancer stemness, invasiveness, and sensitivity to chemotherapies in colon cancer HCT15 cells. Notably, expression of PODXL showed a positive correlation with stem-like and epithelial-mesenchymal transition (EMT) core signatures, and was associated with poor survival outcomes in patients with colon cancer. These findings provide novel insights into the molecular mechanism of PODXL-mediated tumorigenesis in colon cancer.

Panobinostat sensitizes KRAS-mutant non-small-cell lung cancer to gefitinib by targeting TAZ.

Mutation of KRAS in non-small-cell lung cancer (NSCLC) shows a poor response to epidermal growth factor receptor (EGFR) inhibitors and chemotherapy. Currently, there are no direct anti-KRAS therapies available. Thus, new strategies have emerged for targeting KRAS downstream signaling. Panobinostat is a clinically available histone deacetylase inhibitor for treating myelomas and also shows potentiality in NSCLC. However, the therapeutic efficacy of panobinostat against gefitinib-resistant NSCLC is unclear. In this study, we demonstrated that panobinostat overcame resistance to gefitinib in KRAS-mutant/EGFR-wild-type NSCLC. Combined panobinostat and gefitinib synergistically reduced tumor growth in vitro and in vivo. Mechanistically, we identified that panobinostat-but not gefitinib-inhibited TAZ transcription, and the combination of panobinostat and gefitinib synergistically downregulated TAZ and TAZ downstream targets, including EGFR and EGFR ligand. Inhibition of TAZ by panobinostat or short hairpin RNA sensitized KRAS-mutant/EGFR-wild-type NSCLC to gefitinib through abrogating AKT/mammalian target of rapamycin (mTOR) signaling. Clinically, TAZ was positively correlated with EGFR signaling, and coexpression of TAZ/EGFR conferred a poorer prognosis in lung cancer patients. Our findings identify that targeting TAZ-mediated compensatory mechanism is a novel therapeutic approach to overcome gefitinib resistance in KRAS-mutant/EGFR-wild-type NSCLC.