The establishment of kidney cancer organoid line in drug testing.

INTRODUCTION: Kidney cancer is a common urological malignancy worldwide with an increasing incidence in recent years. Among all subtypes, renal cell carcinoma (RCC) represents the most predominant malignancy in kidney. Clinicians faced a major challenge to select the most effective and suitable treatment regime for patients from a wide range of modalities, despite improved understanding and diagnosis of RCC. OBJECTIVE: Recently, organoid culture gained more interest as the 3D model is shown to be highly patient specific which is hypothetically beneficial to the investigation of precision medicine. Nonetheless, the development and application of organotypic culture in RCC is still immature, therefore, the primary objective of this study was to establish an organoid model for RCC. MATERIALS AND METHODS: Patients diagnosed with renal tumor and underwent surgical intervention were recruited. RCC specimen was collected and derived into organoids. Derived organoids were validated by histological examminations, sequencing and xenograft. Drug response of organoids were compared with resistance cell line and patients' clinical outcomes. RESULTS: Our results demonstrated that organoids could be successfully derived from renal tumor and they exhibited high concordance in terms of immunoexpressional patterns. Sequencing results also depicted concordant mutations of driver genes in both organoids and parental tumor tissues. Critical and novel growth factors were discovered during the establishment of organoid model. Besides, organoids derived from renal tumor exhibited tumorigenic properties in vivo. In addition, organoids recapitulated patient's in vivo drug resistance and served as a platform to predict responsiveness of other therapeutic agents. CONCLUSION: Our RCC organoid model recaptiluated histological and genetic features observed in primary tumors. It also served as a potential platform in drug screening for RCC patients, though future studies are necessary before translating the outcomes into clinical practices.

Prognostic Significance of CD163+ and/or CD206+ Tumor-Associated Macrophages Is Linked to Their Spatial Distribution and Tumor-Infiltrating Lymphocytes in Breast Cancer.

Tumor-associated macrophages (TAMs) is a key element in the breast tumor microenvironment. CD163 and CD206 have been utilized for TAM identification, but the clinical implications of TAMs identified by these markers have not been thoroughly explored. This study conducted a comparative analysis of CD163 and CD206 TAMs using digital image analysis, focusing on their spatial distribution and prognostic significance in relation to tumor-infiltrating lymphocytes (TILs). Distinct clinico-pathological and prognostic characteristics were noted between the two types of TAMs. CD163 TAMs were linked to high-grade tumors (p = 0.006), whereas CD206 TAMs were associated with a higher incidence of nodal metastasis (p = 0.033). CD206 TAMs were predominantly found in the stroma, with more cases being stromal CD206-high (sCD206-high) than tumoral CD206-high (tCD206-high) (p = 0.024). Regarding prognostication, patients stratified according to stromal and tumoral densities of CD163 showed different disease-free survival (DFS) time. Specifically, those that were sCD163-low but tCD163-high exhibited the poorest DFS (chi-square = 10.853, p = 0.013). Furthermore, a high sCD163-to-stromal-TILs ratio was identified as an independent predictor of unfavorable survival outcomes (DFS: HR = 3.477, p = 0.018). The spatial distribution and interactions with TILs enhanced the prognostic value of CD163 TAMs, while CD206 TAMs appeared to have limited prognostic utility in breast cancer cases.

Transurethral En Bloc Resection Versus Standard Resection of Bladder Tumour: A Randomised, Multicentre, Phase 3 Trial.

BACKGROUND: Conventionally, standard resection (SR) is performed by resecting the bladder tumour in a piecemeal manner. En bloc resection of the bladder tumour (ERBT) has been proposed as an alternative technique in treating non-muscle-invasive bladder cancer (NMIBC). OBJECTIVE: To investigate whether ERBT could improve the 1-yr recurrence rate of NMIBC, as compared with SR. DESIGN, SETTING, AND PARTICIPANTS: A multicentre, randomised, phase 3 trial was conducted in Hong Kong. Adults with bladder tumour(s) of ≤3 cm were enrolled from April 2017 to December 2020, and followed up until 1 yr after surgery. INTERVENTION: Patients were randomly assigned to receive either ERBT or SR in a 1:1 ratio. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was 1-yr recurrence rate. A modified intention-to-treat analysis on patients with histologically confirmed NMIBC was performed. The main secondary outcomes included detrusor muscle sampling rate, operative time, hospital stay, 30-d complications, any residual or upstaging of disease upon second-look transurethral resection, and 1-yr progression rate. RESULTS AND LIMITATIONS: A total of 350 patients underwent randomisation, and 276 patients were histologically confirmed to have NMIBC. At 1 yr, 31 patients in the ERBT group and 46 in the SR group developed recurrence; the Kaplan-Meier estimate of 1-yr recurrence rates were 29% (95% confidence interval, 18-37) in the ERBT group and 38% (95% confidence interval, 28-46) in the SR group (p = 0.007). Upon a subgroup analysis, patients with 1-3 cm tumour, single tumour, Ta disease, or intermediate-risk NMIBC had a significant benefit from ERBT. None of the patients in the ERBT group and three patients in the SR group developed progression to muscle-invasive bladder cancer; the Kaplan-Meier estimates of 1-yr progression rates were 0% in the ERBT group and 2.6% (95% confidence interval, 0-5.5) in the SR group (p = 0.065). The median operative time was 28 min (interquartile range, 20-45) in the ERBT group and 22 min (interquartile range, 15-30) in the SR group (p < 0.001). All other secondary outcomes were similar in the two groups. CONCLUSIONS: In patients with NMIBC of ≤3 cm, ERBT resulted in a significant reduction in the 1-yr recurrence rate when compared with SR (funded by GRF/ECS, RGC, reference no.: 24116518; ClinicalTrials.gov number, NCT02993211). PATIENT SUMMARY: Conventionally, non-muscle-invasive bladder cancer is treated by resecting the bladder tumour in a piecemeal manner. In this study, we found that en bloc resection, that is, removal of the bladder tumour in one piece, could reduce the 1-yr recurrence rate of non-muscle-invasive bladder cancer.

Deep Learning in Breast Cancer Imaging: A Decade of Progress and Future Directions.

Breast cancer has reached the highest incidence rate worldwide among all malignancies since 2020. Breast imaging plays a significant role in early diagnosis and intervention to improve the outcome of breast cancer patients. In the past decade, deep learning has shown remarkable progress in breast cancer imaging analysis, holding great promise in interpreting the rich information and complex context of breast imaging modalities. Considering the rapid improvement in deep learning technology and the increasing severity of breast cancer, it is critical to summarize past progress and identify future challenges to be addressed. This paper provides an extensive review of deep learning-based breast cancer imaging research, covering studies on mammograms, ultrasound, magnetic resonance imaging, and digital pathology images over the past decade. The major deep learning methods and applications on imaging-based screening, diagnosis, treatment response prediction, and prognosis are elaborated and discussed. Drawn from the findings of this survey, we present a comprehensive discussion of the challenges and potential avenues for future research in deep learning-based breast cancer imaging.

Spatial Distribution and Densities of CD103+ and FoxP3+ Tumor Infiltrating Lymphocytes by Digital Analysis for Outcome Prediction in Breast Cancer.

BACKGROUND: The evaluation of tumor-infiltrating lymphocytes (TILs) for breast cancer prognosis is now established. However, the clinical value for their spatial distributions of specific immune subsets, namely CD103+ tissue-resident memory T cells FoxP3+ regulatory T ells, have not been thoroughly examined. METHOD: Representative whole sections of breast cancers were subjected to CD103 and FoxP3 double staining. Their density, ratio, and spatial features were analyzed in tumor area and tumor-stromal interface. Their associations with clinicopathological parameters and patient's prognosis were analyzed. RESULTS: CD103 TILs were closer to tumor nests than FoxP3 TILs in the tumor-stromal interface. Their densities were associated with high-grade disease, TNBC, and stromal TILs. High stromal FoxP3 (sFoxP3) TILs and close proximity of sCD103 TILs to tumor were independently associated with better survival at multivariate analysis. Subgroup analysis showed the high FoxP3 TILs density associated better survival was seen in HER2-OE and TNBC subtypes while the proximity of CD103 TILs to tumor nests associated better survival was seen in luminal cancers. CONCLUSION: The prognostic impact of CD103 and FoxP3 TILs in breast cancer depends on their spatial localization. High sFoxP3 TIL density and the lower distance of CD103 TILs from the tumor nests had independent favorable prognostic values.

Deep learning-derived spatial organization features on histology images predicts prognosis in colorectal liver metastasis patients after hepatectomy.

Histopathological images of colorectal liver metastases (CRLM) contain rich morphometric information that may predict patients' outcomes. However, to our knowledge, no study has reported any practical deep learning framework based on the histology images of CRLM, and their direct association with prognosis remains largely unknown. In this study, we developed a deep learning-based framework for fully automated tissue classification and quantification of clinically relevant spatial organization features (SOFs) in H&E-stained images of CRLM. The SOFs based risk-scoring system demonstrated a strong and robust prognostic value that is independent of the current clinical risk score (CRS) system in independent clinical cohorts. Our framework enables fully automated tissue classification of H&E images of CRLM, which could significantly reduce assessment subjectivity and the workload of pathologists. The risk-scoring system provides a time- and cost-efficient tool to assist clinical decision-making for patients with CRLM, which could potentially be implemented in clinical practice.

A randomized trial of the effectiveness of an ultrasonic denture hygiene intervention program among community dwelling elders.

Purpose: This study aimed to assess the effectiveness of ultrasonic denture hygiene interventions in improving denture cleanliness among elderly individuals. Materials and methods: Sixty-six participants who had received upper metal framework removable partial dentures within the past 5 years were randomly allocated into three denture hygiene intervention groups: group 1 (mechanical cleaning with a toothbrush and ultrasonic cleaning with cetylpyridinium chloride), group 2 (mechanical cleaning with a toothbrush and ultrasonic cleaning with distilled water), and control (mechanical cleaning with a toothbrush only). Denture cleanliness was assessed at baseline and 1-month using: i) Denture Cleanliness Index (DCI) scores; ii) plaque coverage percentage; and (iii) microbiological samples for bacterial and yeast detection. Differences between groups were assessed with one-way analysis of variance and Chi-squared tests. Results: Mean DCI scores and mean percentages of plaque coverage area were significantly reduced in group 1 and group 2, compared to the control group for both cobalt chromium (CoCr) and acrylic fitting surfaces (p<0.001). No significant differences were found between groups 1 and 2 with regard to the prevalence and viable counts of yeasts or total microbial viable counts. No significant differences in the investigated clinical and microbiological parameters were observed between CoCr and acrylic surfaces following the intervention period. Conclusion: The ultrasonic cleaner was significantly more effective than mechanical cleaning in the reduction of biofilm coverage on metal framework removable partial dentures over a 1-month intervention period. Nevertheless, the adjunctive use of cetylpyridinium chloride with ultrasonic cleaning did not yield additional benefits.

Plasma vaspin levels and clinical outcome in incident peritoneal dialysis patients.

BACKGROUND: Vaspin is an adipokine that regulates glucose and lipid metabolism. Plasma vaspin level is increased in chronic kidney disease but decreased in hemodialysis patients. However, plasma vaspin level in peritoneal dialysis (PD) patients, as well as its prognostic role, has not been studied. METHODS: We recruited 146 incident PD patients. Their baseline plasma vaspin levels, body anthropometry, the profile of insulin resistance, bioimpedance spectroscopy parameters, dialysis adequacy, and nutritional indices were measured. They were followed for up to 5 years for survival analysis. RESULTS: The average age was 58.4 ± 11.8 years; 96 patients (65.8%) were men, and 90 (61.6%) had diabetes. The median vaspin level was 0.18 ng/dL (interquartile range [IQR] 0.11 to 0.30 ng/dL). Plasma vaspin level did not have a significant correlation with adipose tissue mass or baseline insulin level. However, plasma vaspin level had a modest correlation with the change in insulin resistance, as represented by the HOMA-IR index, in non-diabetic patients (r = -0.358, p = 0.048). Although the plasma vaspin level quartile did not have a significant association with patient survival in the entire cohort, it had a significant interaction with diabetic status (p < 0.001). In nondiabetic patients, plasma vaspin level quartile was an independent predictor of patient survival after adjusting for confounding clinical factors (adjusted hazard ratio 2.038, 95% confidence interval 1.191-3.487, p = 0.009), while the result for diabetic patients was not significant. CONCLUSIONS: Plasma vaspin level quartile had a significant association with patient survival in non-diabetic PD patients. Baseline plasma vaspin level also had a modest inverse correlation with the subsequent change in the severity of insulin resistance, but the exact biological role of vaspin deserves further studies.

A proof-of-concept study on endoscopic ultrasound-guided biopsy of detrusor muscle in porcine bladders.

Introduction: Conventionally, we rely on transurethral resection of bladder tumour (TURBT) for local staging of muscle-invasive bladder cancer (MIBC). However, the procedure is limited by its staging inaccuracy which may delay the definitive treatment of MIBC. Methods: We conducted a proof-of concept study on endoscopic ultrasound (EUS)-guided biopsy of detrusor muscle in porcine bladders. Five porcine bladders were used in this experiment. Upon EUS, four layers of tissue including the mucosa (hypoechoic), submucosa (hyperechoic), detrusor muscle (hypoechoic) and serosa (hyperechoic) could be identified. Results: A total of 37 EUS-guided biopsies were taken from 15 sites (three sites per bladder), and the mean number of biopsies taken from each site was 2.47±0.64. Among the 37 biopsies, 30 of them (81.1%) obtained detrusor muscle in the biopsy specimen. For the per biopsy site analysis, detrusor muscle was obtained in 73.3% if only one biopsy was taken, and 100% if two or more biopsies were taken from the same biopsy site. Overall, detrusor muscle was successfully obtained from all 15 biopsy sites (100%). No bladder perforation was observed throughout all biopsy processes. Conclusion: EUS-guided biopsy of the detrusor muscle could be performed during the initial cystoscopy session, thus expediting the histological diagnosis and subsequent treatment of MIBC.

Word reading transfer in two distinct languages in reading interventions: How Chinese-English bilingual children with reading difficulties learn to read.

PURPOSE: Skills developed from literacy training in L1 are shown to transfer to reading in L2 when both languages involve an alphabetic writing system. However, transfer of literacy skills between a logographic L1 and an alphabetic L2 is less studied. This study examined whether the gain in literacy skills after an 8-week training on 1) Chinese character recognition or 2) English phonics, may generalize across the two languages in Chinese elementary students with reading disabilities. METHODS: Chinese-speaking students identified with reading difficulties were randomly assigned to the Chinese intervention (Chinese character orthography training), English intervention (English phonics training), and control groups. Their Chinese and English literacy skills were measured before and after the interventions. RESULTS: Though training on the orthography of Chinese characters significantly improved performance in Chinese word reading and Chinese orthographic awareness, our results did not provide evidence for the generalization of word-decoding skills from L1 Chinese to word reading in L2 English. However, phonics training in L2 English benefitted not only English word reading, but also cross-language word reading in L1 Chinese. CONCLUSION: We postulated that teaching children analytical skills in decoding words in an alphabetic writing system might likewise benefit their word decoding in a logographic script.

Omentin-1 Levels and Outcomes in Incident Peritoneal Dialysis Patients.

Rationale & Objective: Omentin-1 is an adipokine with anti-inflammatory and cardioprotective properties. The objective of this study was to determine the prognostic role of plasma omentin-1 levels in incident peritoneal dialysis (PD) patients. Study Design: Retrospective analysis of prospective cohort. Setting & Participants: 152 incident PD patients. Predictors: Plasma omentin-1 level, adipose tissue omentin-1 messenger RNA (mRNA) expression. Outcomes: Patient survival, technique survival, hospital admission, and duration of stay. Analytical Approach: Time-to-event survival analyses; linear regression for hospitalization. Results: The mean age was 58.4 ± 11.7 years; 102 were men, and 92 had diabetes. There was no significant correlation between plasma omentin-1 level and its adipose tissue mRNA expression. A higher plasma omentin-1 level quartile was not associated with patient survival (P = 0.92) or technique survival (P = 0.83) but had a modest correlation with a lower number of hospital admissions (P = 0.07) and shorter duration of hospital stay (P = 0.04). In adjusted models using multivariable linear regression, a higher plasma omentin-1 level quartile remained significantly associated with fewer hospital admissions (ß, -0.13; 95% CI, -0.26 to -0.002; P = 0.05) and shorter hospitalization duration (ß, -0.20; 95% CI, -0.38 to -0.02; P = 0.03). Limitations: Observational study with baseline measures only. Conclusions: Plasma omentin-1 level was not associated with patient survival, technique survival, or peritonitis, but higher plasma omentin-1 levels were associated with fewer hospital admissions and shorter duration of hospitalization among incident PD patients.

Number Needed to Diagnose in Malignant Ascites: Effects of Volume, Repeating Collection, and Primary Malignancy on Diagnostic Performance in Peritoneal Fluid Cytology.

INTRODUCTION: Volume recommendations of 80-200 mL have been proposed for peritoneal fluid cytology. While cutoffs are impractical when volume is limited by the amount present and disease factors, collections, however, can be repeated. This study addresses adequacy and number needed to diagnose by comparing diagnostic agreement to volumes in single specimens, total volumes collected daily, and within admissions. The diagnostic yield of repeating collection within a single day, admission, and throughout admissions of a patient's lifetime was also investigated. METHODS: Peritoneal fluid cytology specimens over a 27-year period were retrieved and matched by collection date, admission number, and patient number. Case notes were reviewed to establish all cases of malignant ascites. RESULTS: In total, 19,392 specimens from 14,327 admissions and 11,089 patients were retrieved, with 1,531 patients confirmed with malignant ascites. Agreements between cytologic diagnoses within the same day and admission were high (κ > 0.8). Fluid volume increased with grade of cytologic diagnosis (p < 0.001), and greater volume was associated with higher discordance (p < 0.05). Specimens of 60-100 mL showed the best diagnostic concordance. To achieve a 99.5% diagnostic rate, three sequential aliquots, collections from two different days in an admission, or three admissions within a lifetime are required. The diagnostic yield of one aliquot within batches from the same day was only 88.9%. Gastrointestinal (p = 0.040), gynecologic (p = 0.005), and lung (p < 0.001) malignancies required the least repeats for diagnosis. CONCLUSIONS: Omission of any fluid from laboratory submission is strongly discouraged. As a simple rule, three repeats are necessary for excluding malignant ascites.

Circulating and Adipose Tissue Adiponectin Level and Outcomes in Incident Peritoneal Dialysis Patients.

Rationale & Objective: Cardiovascular disease is the major cause of mortality and morbidity in peritoneal dialysis (PD) patients. Adiponectin, a key adipokine, is related to obesity and insulin resistance. We determined the clinical and prognostic value of plasma adiponectin level and its adipose tissue messenger RNA (mRNA) expression in new PD patients. Study Design: Retrospective analysis of a prospective observational study. Setting & Participants: 152 new PD patients from a single center; 6 adults undergoing abdominal surgeries without kidney disease served as controls. Predictors: Plasma adiponectin level and its adipose tissue mRNA expression. Outcomes: Body build and composition, patient and technique survival. Analytical Approach: Adiponectin level and mRNA expression were grouped in quartiles for correlation analysis for body build and Cox regression for survival analysis. Results: The median plasma adiponectin level was 31.98 µg/mL (IQR, 16.81-49.49 µg/mL), and adiponectin mRNA expression in adipose tissue was 1.65 times higher than in controls (IQR, 0.98-2.63). There was a modest but statistically significant correlation between plasma adiponectin and its adipose tissue mRNA expression (r = 0.40, P < 0.001). Plasma adiponectin level inversely correlated with body mass index, waist-hip ratio, mid-arm circumference, adipose tissue mass, plasma triglyceride (r = -0.39, -0.38, -0.41, -0.38, and -0.30, respectively; P < 0.001 for all), as well as serum insulin level (r = -0.24, P = 0.005). Similar correlations were present but less marked with adipose tissue adiponectin mRNA level. Neither plasma adiponectin level nor adipose tissue adiponectin mRNA level predicted patient or technique survival. Limitations: Observational study, single center, single baseline measurement. Conclusions: Plasma adiponectin level correlated with the degree of adiposity in new PD patients. However, neither plasma adiponectin level nor its adipose tissue mRNA expression was an independent prognostic indicator in kidney failure patients newly started on PD.

A comparative study of diagnostic accuracy in 3026 pleural biopsies and matched pleural effusion cytology with clinical correlation.

BACKGROUND: Pleural effusion can be caused by a wide range of benign and malignant conditions. Pleural biopsy and effusion cytology represent two key methods of pathological diagnosis. To compare the performance these two methods, a large cohort of matched pleural biopsy and effusion cytology with clinical follow-up was reviewed. METHODS: Pleural biopsies and effusion cytology specimens over a period of 18 years were retrieved. Cytology specimens collected within 7 days of pleural biopsy were matched. Reports were reviewed, and the cause for pleural effusion was determined by hospital disease coding and clinical data. RESULTS: Totally, 3026 cases were included. The leading cause of benign effusion was tuberculosis (n = 650). Malignant pleural effusion (MPE) was more common in older females (p < 0.001) and mostly due to lung cancer (n = 959), breast cancer (n = 64), and mesothelioma (n = 48). The inadequate/insufficient (B1/C1) rate of biopsy was higher than cytology (15.6% vs. 0.3%) but the rates for other diagnostic categories were similar. Biopsy and cytology showed a correlation coefficient of 0.315, improving to 0.449 when inadequate/insufficient (B1/C1) cases were excluded. The ROM for benign cytology (C2) was lower than biopsy (B2) (p < 0.001). Compared with biopsy, the diagnostic accuracy was higher in cytology overall and for metastatic carcinomas (p < 0.001) but lower for hematolymphoid malignancies (p = 0.014) and mesotheliomas (p = 0.002). CONCLUSIONS: These results suggest that effusion cytology may be better for confirming benignity and diagnosing carcinomatous MPE. In these cases, pleural biopsy may be withheld to reduce procedural risks. However, for suspected hematolymphoid malignancies and mesothelioma, biopsy should be considered.

Artificial intelligence in breast cancer histopathology.

This is a review on the use of artificial intelligence for digital breast pathology. A systematic search on PubMed was conducted, identifying 17,324 research papers related to breast cancer pathology. Following a semimanual screening, 664 papers were retrieved and pursued. The papers are grouped into six major tasks performed by pathologists-namely, molecular and hormonal analysis, grading, mitotic figure counting, ki-67 indexing, tumour-infiltrating lymphocyte assessment, and lymph node metastases identification. Under each task, open-source datasets for research to build artificial intelligence (AI) tools are also listed. Many AI tools showed promise and demonstrated feasibility in the automation of routine pathology investigations. We expect continued growth of AI in this field as new algorithms mature.

Idiopathic granulomatous mastitis and cystic neutrophilic granulomatous mastitis: two sides of the same coin or distinct entities?

Idiopathic granulomatous mastitis (IGM) is a benign mimic of breast carcinomas. It is defined histologically by the presence of granulomas and inflammation. The closely related cystic neutrophilic granulomatous mastitis (CNGM) shows lipogranulomas, with a reported association with corynebacteria. A large cohort of IGM was reviewed to compare clinical, microbiological and histological features between non-CNGM IGM and CNGM. Cases of IGM were reviewed for histological parameters including the presence of lipogranulomas and composition of inflammatory cells. Clinical data were obtained through hospital records. The cohort included 79 cases, including 51 non-CNGM IGM and 28 CNGM. Comparing non-CNGM IGM and CNGM, there were no differences in clinical or demographical data, other than a younger age of presentation (36.2 vs 41.5 years, p=0.012) for CNGM. Most IGM resolved within the follow-up period (n=57/64, 89.1%), with similar outcomes regardless of treatment (p>0.05). In CNGM, there were more infiltrates of neutrophils (p=0.001), histiocytes (p=0.047), and multinucleated giant cells (p=0.006), but less lymphocytes (p=0.008). Corynebacteria was cultured in two (25%) cases of CNGM, and one non-CNGM IGM (14.3%). Gram-positive bacilli were identified in two cases of CNGM. 'Early' lipogranulomas were observed closely associated to inflamed ducts in three cases of CNGM. Apart from age, there was no distinct clinical or microbiological feature for CNGM. These findings do not support CNGM as a distinct entity. Rather, CNGM-pattern may represent a continuum of IGM, possibly age-related and attributable to ductal inflammation and cystic changes in the breast parenchyma.

Deep learning for computational cytology: A survey.

Computational cytology is a critical, rapid-developing, yet challenging topic in medical image computing concerned with analyzing digitized cytology images by computer-aided technologies for cancer screening. Recently, an increasing number of deep learning (DL) approaches have made significant achievements in medical image analysis, leading to boosting publications of cytological studies. In this article, we survey more than 120 publications of DL-based cytology image analysis to investigate the advanced methods and comprehensive applications. We first introduce various deep learning schemes, including fully supervised, weakly supervised, unsupervised, and transfer learning. Then, we systematically summarize public datasets, evaluation metrics, versatile cytology image analysis applications including cell classification, slide-level cancer screening, nuclei or cell detection and segmentation. Finally, we discuss current challenges and potential research directions of computational cytology.

Adipose and Plasma microRNAs miR-221 and 222 Associate with Obesity, Insulin Resistance, and New Onset Diabetes after Peritoneal Dialysis.

BACKGROUND: The correlation between microRNA, obesity, and glycemic intolerance in patients on peritoneal dialysis (PD) is unknown. We aimed to measure the adipose and plasma miR-221 and -222 levels, and to evaluate their association with adiposity, glucose intolerance, and new onset diabetes mellitus (NODM) after the commencement of PD. METHODS: We prospectively recruited incident adult PD patients. miR-221 and -222 were measured from adipose tissue and plasma obtained during PD catheter insertion. These patients were followed for 24 months, and the outcomes were changes in adiposity, insulin resistance, and NODM after PD. RESULTS: One hundred and sixty-five patients were recruited. Patients with pre-existing DM had higher adipose miR-221 (1.1 ± 1.2 vs. 0.7 ± 0.9-fold, p = 0.02) and -222 (1.9 ± 2.0 vs. 1.2 ± 1.3-fold, p = 0.01). High adipose miR-221 and -222 levels were associated with a greater increase in waist circumference (miR-221: beta 1.82, 95% CI 0.57-3.07, p = 0.005; miR-222: beta 1.35, 95% CI 0.08-2.63, p = 0.038), Homeostatic Model Assessment for Insulin Resistance (HOMA) index (miR-221: beta 8.16, 95% CI 2.80-13.53, p = 0.003; miR-222: beta 6.59, 95% CI 1.13-12.05, p = 0.018), and insulin requirements (miR-221: beta 0.05, 95% CI 0.006-0.09, p = 0.02; miR-222: beta 0.06, 95% CI 0.02-0.11, p = 0.002) after PD. The plasma miR-222 level predicted the onset of NODM (OR 8.25, 95% CI 1.35-50.5, p = 0.02). CONCLUSION: miR-221 and -222 are associated with the progression of obesity, insulin resistance, and NODM after PD.

EGFR testing in paraffin-embedded cell block cytology material is reliable with increased detection for effusion fluid.

INTRODUCTION: Cytology is integral to lung cancer diagnosis. Aspiration and exfoliative fluid specimens represent valuable tumor material for molecular testing. In this study, a large retrospective cohort of EGFR tests was reviewed to address the adequacy, detection and discrepancy rate in tests performed with cytology material. METHODS: EGFR tests performed from 2013 to 2022 were reviewed and classified by the modality of obtaining tissue and by tissue type. EGFR tests for tissue specimens were performed on unstained sections of paraffin-embedded material on glass slides. Adequacy and types of mutation(s) detected were analysed. Cases where multiple EGFR testing was performed on the same patient were reviewed for discordance. RESULTS: There were 5,504 tests retrieved, with 1,855, 3,607 and 42 performed on cytology, surgical and blood specimens. Lung and excision specimens were more often adequate (p < 0.001). Cytology material showed lower adequacy rates (p < 0.01). EGFR detection (positive) rate was higher in pleural fluid compared to biopsy (59.8 % vs 50.7 %, p = 0.022), but similar between lung and lymph node cytology and non-cytology specimens. Effusion fluid specimens had the highest adequacy (81.5 %) and detection rate (59.3 %) among cytology specimens (p < 0.001). Four (4.4 %) cases showed discordant results in cytology specimens. Two were false negatives in the non-cytology material. Only in one case was cytology material genuinely discrepant. The remaining discordance was attributed to the interval treatment effect. CONCLUSION: The findings support that EGFR testing in cell block is reliable and complements tissue material. In addition, pleural fluid appears to be superior to pleural biopsies for molecular testing.