A Thalamic Orphan Receptor Drives Variability in Short-Term Memory.

Working memory is a form of short-term memory that involves maintaining and updating task-relevant information toward goal-directed pursuits. Classical models posit persistent activity in prefrontal cortex (PFC) as a primary neural correlate, but emerging views suggest additional mechanisms may exist. We screened ∼200 genetically diverse mice on a working memory task and identified a genetic locus on chromosome 5 that contributes to a substantial proportion (17%) of the phenotypic variance. Within the locus, we identified a gene encoding an orphan G-protein-coupled receptor, Gpr12, which is sufficient to drive substantial and bidirectional changes in working memory. Molecular, cellular, and imaging studies revealed that Gpr12 enables high thalamus-PFC synchrony to support memory maintenance and choice accuracy. These findings identify an orphan receptor as a potent modifier of short-term memory and supplement classical PFC-based models with an emerging thalamus-centric framework for the mechanistic understanding of working memory.

Cervical cancer prevention and control in women living with human immunodeficiency virus.

Despite being highly preventable, cervical cancer is the fourth most common cancer and cause of cancer death in women globally. In low-income countries, cervical cancer is often the leading cause of cancer-related morbidity and mortality. Women living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome are at a particularly high risk of cervical cancer because of an impaired immune response to human papillomavirus, the obligate cause of virtually all cervical cancers. Globally, approximately 1 in 20 cervical cancers is attributable to HIV; in sub-Saharan Africa, approximately 1 in 5 cervical cancers is due to HIV. Here, the authors provide a critical appraisal of the evidence to date on the impact of HIV disease on cervical cancer risk, describe key methodologic issues, and frame the key outstanding research questions, especially as they apply to ongoing global efforts for prevention and control of cervical cancer. Expanded efforts to integrate HIV care with cervical cancer prevention and control, and vice versa, could assist the global effort to eliminate cervical cancer as a public health problem.

Effect of Vaginal Microecological Disorders on the Increased Risk of Abnormal Cervical Cytology Among Women With Human Immunodeficiency Virus in China.

BACKGROUND: Abnormal cervical cytology is commonly observed in women with human immunodeficiency virus (WWH). METHODS: A cross-sectional study was conducted with 130 WWH and 147 age-matched healthy controls, who underwent gynecological examinations at Beijing Ditan Hospital. The presence of abnormal cervical cytology in WWH was predicted after performing a logistic regression analysis. RESULTS: Multivariate logistic regression revealed 3 independent factors, among which CD4 cell count ≥350 cells/µL was the protective factor, while human papillomavirus infection and abnormal vaginal pH were the risk factors. CONCLUSIONS: Vaginal microecological disorders can increase the risk of abnormal cervical cytology in WWH.

Cumulative Detection of Anal High-Grade Squamous Intraepithelial Lesions Over 2-Year Follow-up in Men Who Have Sex With Men Living With Human Immunodeficiency Virus in France.

We assessed cumulative detection and determinants of anal high-grade squamous intraepithelial lesions (HSILs) in men who have sex with men living with human immunodeficiency virus and who underwent 3 visits over 2 years, with cytology and high-resolution anoscopy, within the ANRS-EP57-APACHES study. The cumulative HSIL detection rate was 33% (134 of 410), of which 48% HSILs were detected at baseline. HSIL detection varied considerably by center (from 13% to 51%). The strongest HSIL determinants were baseline human papillomavirus 16 (adjusted odds ratio, 8.2; 95% confidence interval, 3.6-18.9) and p16/Ki67 (4.6 [2.3-9.1]). Repeated annual cytology and high-resolution anoscopy improved HSIL detection but did not fully compensate for between-center heterogeneity.

Two-Year Incidence and Cumulative Risk and Predictors of Anal High-Grade Squamous Intraepithelial Lesions (Anal Precancer) Among Women With Human Immunodeficiency Virus.

BACKGROUND: Detection and treatment of anal histologic high-grade squamous intraepithelial lesions (hHSIL) prevents anal cancer. However, anal hHSIL incidence among women with human immunodeficiency virus (HIV, WHIV) remains unknown. Performance of anal high-risk human papillomavirus ([hr]HPV), anal cytology (anal-cyt), and both for hHSIL detection longitudinally over 2 years also remains undetermined. METHODS: We determined 2-year incidence and cumulative risk estimates (2-y-CR) of anal hHSIL among WHIV using prevalence and incidence (per 100 person-years [py]) observations stratified by baseline hrHPV and/or anal-cyt results. RESULTS: In total, 229 WHIV with complete baseline data were included in the analysis; 114 women without prevalent anal hHSIL were followed with 2 annual evaluations. Median age was 51, 63% were Black, and 23% were Hispanic. Anal hrHPV or abnormal anal-cyt was associated with an increased risk of incident anal hHSIL at 2 years (18.9/100py [95% confidence interval {CI} 11.4-31.3] and 13.4/100py [95% CI 8.0-22.7], respectively) compared with no detection of anal HPV or negative cytology (2.8/100py [95% CI 1.1-7.4] and 4.2 [95% CI, 1.8-10.2]) The presence of anal hrHPV with abnormal cytology was associated with 2-y-CR of anal hHSIL of 65.6% (95% CI 55.4%-75%); negative hrHPV with negative cytology was associated with 2-y-CR of anal hHSIL of 9.2% (95% CI 7.0-16.0). CONCLUSIONS: Detection of anal hrHPV or abnormal anal cytology are comparable predictors for 2-y-CR of anal hHSIL. The absence of anal hrHPV combined with negative cytology was predictive of a lower (but measurable) risk of developing anal hHSIL. These findings provide important data to inform anal cancer screening guidelines for WHIV.

Clinically validated HPV assays offer comparable long-term safety in primary cervical cancer screening: A 9-year follow-up of a population-based screening cohort.

Molecular testing for human papillomaviruses (HPV) is gradually replacing cytology in cervical cancer screening. In this longitudinal population-based cohort study, 4140 women 20 to 64 years old attending organized screening were tested at baseline by five different screening methods and followed for 9 years. To assess long-term safety, the cumulative risks of CIN2+/CIN3+ were estimated after a negative baseline result obtained by conventional cytology and four clinically validated HPV assays: Hybrid Capture 2 (hc2), RealTime High Risk HPV assay (RealTime), cobas 4800 HPV Test (cobas_4800), and Alinity m HR HPV (Alinity). HPV-negative women at baseline had a substantially lower risk for CIN2+ compared to those with normal baseline cytology: 0.84% (95% CI, 0.46-1.22), 0.90% (95% CI, 0.51-1.29), 0.78% (95% CI, 0.42-1.15), and 0.75% (95% CI, 0.39-1.11) for hc2, RealTime, cobas_4800, and Alinity, respectively, compared to 2.46% (95% CI, 1.88-3.03) for cytology. No differences were observed between HPV assays in longitudinal sensitivity (range: 86.21%-90.36%) and negative predictive values (range: 99.54%-99.70%) for CIN2+ in women ≥30 years, but were significantly different from cytology (p < .05). The 9-year cumulative risk of CIN2+ differed significantly between HPV genotypes, reaching 32.1% (95% CI, 14.5-46.1) for HPV16, 24.9% (95% CI, 4.7-40.8) for HPV18/45, 27.2% (95% CI, 14.6-37.8) for HPV31/33/35/52/58, and 8.1% (95% CI, 0.0-16.7) for HPV39/51/56/59. Four clinically validated HPV assays showed comparable safety and better assurance against precancerous lesions than cytology, but some important differences were identified in the performance characteristics of HPV assays impacting the referral rate. Information about the HPV genotype is valuable for guiding further clinical action in HPV-based screening programs.

Self-collected versus clinician-collected anal swabs for anal cancer screening: A systematic review and meta-analysis.

Anal squamous cell carcinoma (ASCC) incidence is increasing globally. International consensus guidelines published in 2024 include HPV and/or cytology testing of anal swabs in those at greatest risk of ASCC. Self-collected anal swabs may be important for increasing screening uptake, but evidence is needed as to their equivalence to clinician-collected swabs. We searched Medline, Embase, Cochrane Library, and CINAHL databases for publications to 13 June 2023. Studies were included if reporting data on HPV testing, cytology testing, or acceptability, for both self- and clinician-collected anal swabs. Risk of bias was assessed using the QUADAS-2 assessment tool. The primary outcome was HPV and cytology sampling adequacy. Secondary outcomes were HPV and cytology results, and acceptability of collection methods. Thirteen papers describing 10 studies were eligible. Sample adequacy was comparable between self- and clinician-collected swabs for HPV testing (meta-adequacy ratio: 1.01 [95% CI 0.97-1.05]) but slightly lower for cytology by self-collection (meta-adequacy ratio: 0.91 [95% CI 0.88-0.95]). There was no significant difference in prevalence (meta-prevalence ratio: 0.83 (95% CI 0.65-1.07) for any HR-HPV, 0.98 (95% CI 0.84-1.14) for any HPV, and 0.68 (95% CI 0.33-1.37) for HPV16), or any cytological abnormality (meta-prevalence ratio 1.01 [95% CI 0.86-1.18]). Only three papers reported acceptability results. Findings indicate self-collection gives equivalent sample adequacy for HPV testing and ~ 10% inferior adequacy for cytological testing. Meta-prevalence was similar for HPV and cytology, but confidence intervals were wide. Larger studies are required to definitively assess use of self-collected swabs in anal cancer screening programs, including acceptability.

International Anal Neoplasia Society's consensus guidelines for anal cancer screening.

The International Anal Neoplasia Society (IANS) developed consensus guidelines to inform anal cancer screening use among various high-risk groups. Anal cancer incidence estimates by age among risk groups provided the basis to identify risk thresholds to recommend screening. Guided by risk thresholds, screening initiation at age 35 years was recommended for men who have sex with men (MSM) and transgender women (TW) with HIV. For other people with HIV and MSM and TW not with HIV, screening initiation at age 45 years was recommended. For solid organ transplant recipients, screening initiation beginning from 10 years post-transplant was recommended. For persons with a history of vulvar precancer or cancer, screening initiation was recommended starting within 1 year of diagnosis of vulvar precancer or cancer. Persons aged ≥45 years with a history of cervical/vaginal HSIL or cancer, perianal warts, persistent (>1 year) cervical HPV16, or autoimmune conditions could be considered for screening with shared decision-making, provided there is adequate capacity to perform diagnostic procedures (high-resolution anoscopy [HRA]). Anal cytology, high-risk (hr) human papillomavirus (HPV) testing (including genotyping for HPV16), and hrHPV-cytology co-testing are different strategies currently used for anal cancer screening that show acceptable performance. Thresholds for referral for HRA or follow-up screening tests are delineated. These recommendations from IANS provide the basis to inform management of abnormal screening results, considering currently available screening tools. These guidelines provide a pivotal foundation to help generate consensus among providers and inform the introduction and implementation of risk-targeted screening for anal cancer prevention.

Long-term follow-up of cervical cancer incidence after normal cytological findings.

An increase in cervical cancer incidence in Sweden from 2014 to 2015 has been attributed to an increase in false-negative cytological findings before cancer diagnoses. Years later, we performed a long-term follow-up to investigate whether the problem persisted. At each calendar year from 2016 to 2020, we identified women with prior normal cervical screening results through linkage to the Swedish National Cervical Screening Registry. We reported their incidence rates (IRs) of invasive cervical cancer in consecutive years and compared the IRs over time. For the years 2016 to 2020, there was no overall change in cervical cancer incidence after two normal cytology in the last two screening intervals. However, there was a further 62% increase among women 50 to 60 years of age with normal cytology in the past two screening intervals. The incidence rate of cervical cancer was high among nonscreened women and low among HPV-screened women with negative results, with no trends over time. Our results imply that the previously reported decrease in sensitivity of cervical cytology is persisting. Although primary cytology screening is no longer used, cytology is used in triaging among HPV-positive women. Our findings suggest that improved triaging is needed, for example, improved quality assurance and/or use of alternative triage tests.

Is prostatic adenocarcinoma detectable by urine cytology-A multicenter retrospective review.

INTRODUCTION: Urine cytology is robust for the diagnosis of urothelial lesions, but data on the detection rates of prostatic adenocarcinoma in urine cytology is limited. In this study, a multicenter review was performed to define the clinical role of urine cytology in diagnosis of prostatic adenocarcinoma. METHODS: Cytologic diagnoses of lower tract urine cytology specimens with histology-proven prostatic adenocarcinoma from three institutions, from a period of over two decades, were reviewed. Clinicopathological parameters-tumor grade, stage, histologic features, and preanalytical factors-prostate-specific antigen (PSA) level and lesion size, were retrieved and compared with cytologic diagnoses. RESULTS: In total, 2115 urine cytology specimens from 1119 patients were retrieved. The atypia (or above/C3+) and suspicious (or above/C4+) rates were 19.48% and 3.36%. Bilobar and extracapsular involvement, lymphovascular invasion, Gleason score, and International Society of Urological Pathology grade were associated with a positive urine diagnosis (p < 0.05). The atypia (C3+) and suspicious (C4+) rates of urine cytology in patients with a PSA level of ≤4.0 ng/mL was paradoxically higher (p < 0.01), but PSA levels correlated positively with urine diagnosis at higher cutoffs (>10, >20, >50, >100 ng/mL). All these factors remained significant on multivariate analysis (p < 0.05), including a negative correlation with low-PSA (≤4.0 ng/mL, p = 0.001) and positive correlation with high-PSA (>20 ng/mL, p = 0.020). Lesion size and multifocality were not associated with urine cytology diagnosis (p > 0.05). CONCLUSION: Urine cytology showed low sensitivity in detection of prostatic adenocarcinoma. Detection rates were largely positively correlated with PSA levels but not for lesion size nor multifocality, limiting its clinical utility.

Phase 1 trial of intraperitoneal paclitaxel in patients with gastric adenocarcinoma and carcinomatosis or positive cytology.

BACKGROUND: The purpose of this phase 1 trial was to evaluate the safety and toxicity of repeated normothermic intraperitoneal paclitaxel (PTX) for patients with gastric cancer metastatic to the peritoneum. METHODS: A Bayesian optimal interval design was used to prospectively identify the safety and tolerability of escalating doses of intraperitoneal paclitaxel at weekly treatments for 3 weeks, followed by a 1-week break, and then three additional treatments. The primary objective was to define the maximum tolerated dose. Secondary end points included safety, tolerability, and antitumor activity. RESULTS: A total of 25 patients were treated between January 2020 and April 2023. Five dose-limiting toxicities were observed at 100 mg/m2. Treatment-related grade 3-4 toxicity included leukopenia (32%) and neutropenia (32%). Seven patients required a schedule change to every other week treatments. The maximum tolerated dose for intraperitoneal PTX was 100 mg/m2. The peritoneum post-intraperitoneal PTX demonstrated progression in five (20%), stable disease in five (20%), improvement in 10 (40%), and not evaluable in five (20%). Eight patients (32%) had resolution of their peritoneal disease and seven (28%) underwent attempted resection. The median overall survival (OS) from the diagnosis of metastatic disease was 18.8 months and from the date of treatment initiation was 10.8 months. One-, 2-, and 3-year OS rates from the diagnosis of metastatic disease were 84%, 38%, and 25%, respectively. CONCLUSIONS: Paclitaxel may be safely used at intraperitoneal doses of 100 mg/m2. Neutropenia associated with weekly treatments was common. Peritoneal complete clinical response rates with multimodality therapy including PTX were promising.

Contemporary Management of Thyroid Nodules.

Thyroid nodules are common in the general population, with higher prevalence in women and with advancing age. Approximately 5% of thyroid nodules are malignant; the majority of this subset represents papillary thyroid cancer. Ultrasonography is the standard technique to assess the underlying thyroid parenchyma, characterize the features of thyroid nodules, and evaluate for abnormal cervical lymphadenopathy. Various risk stratification systems exist to categorize the risk of malignancy based on the ultrasound appearance of a thyroid nodule. Nodules are selected for fine-needle aspiration biopsy on the basis of ultrasound features, size, and high-risk clinical history. Cytology results are classified by the Bethesda system into six categories ranging from benign to malignant. When cytology is indeterminate, molecular testing can further risk-stratify patients for observation or surgery. Surveillance is indicated for nodules with benign cytology, indeterminate cytology with reassuring molecular testing, or non-biopsied nodules without a benign sonographic appearance.

Platelet aggregates in lung capillaries in severely decompensated pulmonary hypertension.

The mechanism of thrombocytopenia during acute pulmonary hypertension (PH) decompensation may be partly due to platelet aggregation in the lung. Platelet aggregates in explanted lung from 16 lung transplant patients during acute PH decompensation with and without thrombocytopenia were identified by immunohistochemistry. Scanning electron microscopy (SEM) was performed. 7 explant lung controls without PH and thrombocytopenia were also examined. Compared with controls, the median number of platelet aggregates was higher in patients with acute PH decompensation with thrombocytopenia (19.4 [IQR 3.4-38.3] vs 147.5 [IQR 26.5-203.2]). SEM showed capillaries filled with platelet aggregates. Our study suggests that platelets may aggregate in the lungs during acute PH decompensation.

Pulmonary fibrosis and lung cancer: an analysis of the Clinical Practice Research Datalink linked to the National Cancer Registration Dataset.

We quantified the proportion of diagnoses of pulmonary fibrosis (PF) among 25 136 people with lung cancer and 250 583 matched controls and compared the natural history of lung cancer in people with and without PF. Diagnoses of PF were more common in people with lung cancer than those without (1.5% vs 0.8%, OR 1.97; 95% CI 1.77 to 2.21). Within people with PF, squamous cell carcinoma was more (22.9% vs 19.1%), and adenocarcinoma was less common (18.0% vs 21.3%). People with PF were less likely to have stage 4 disease at diagnosis (OR 0.43, 95% CI 0.28 to 0.65) but their survival was worse.

Long-Term Outcomes of Endoscopic Ultrasound-Guided Ablation Vs Surgery for Pancreatic Cystic Tumors.

BACKGROUND & AIMS: Endoscopic ultrasound-guided pancreatic cyst ablation (EUS-PCA) is performed as an alternative to surgical resection in selected patients with pancreatic cystic tumors (PCTs). We aimed to directly compare the long-term outcomes between EUS-PCA and surgery for PCTs. METHODS: We reviewed a PCT database to identify patients with unilocular or oligolocular PCTs who underwent EUS-PCA or surgery between January 2004 and July 2019. We performed 1:1 propensity score matching based on potential confounding factors. The primary outcome was long-term morbidities. Secondary outcomes included early (≤14 days) and late (>14 days) major adverse events (MAEs), development of diabetes mellitus, readmission, length of hospital stay, and therapeutic efficacy. RESULTS: A total of 620 patients (EUS-PCA, n = 310; surgery, n = 310) were selected after propensity score matching. The EUS-PCA group showed a lower 10-year rate of cumulative long-term morbidities (1.6% vs 33.5%; P = .001) as well as lower rates of early MAE (1.0% vs 8.7%; P = .001), late MAE (0.3% vs 5.5%; P = .001), and readmission (1.0% vs 15.2%; P = .001). The EUS-PCA group had a shorter hospital stay (3.5 vs 10.3 d; P = .001) and a lower incidence of diabetes mellitus (2.2% vs 22.8%; P = .001), whereas the surgery group had a higher complete resolution rate (76.5% vs 100%; P = .001) and a lower relapse rate (4.6% vs 0.3%; P = .001). CONCLUSIONS: For select patients with PCTs, EUS-PCA showed superior results to surgery in terms of long-term safety profile and preservation of pancreatic function.

Stomatal penetration: the cornerstone of plant resistance to the fungal pathogen Zymoseptoria tritici.

BACKGROUND: Septoria tritici blotch (STB), caused by the foliar fungus Zymoseptoria tritici, is one of the most damaging disease of wheat in Europe. Genetic resistance against this fungus relies on different types of resistance from non-host resistance (NHR) and host species specific resistance (HSSR) to host resistance mediated by quantitative trait loci (QTLs) or major resistance genes (Stb). Characterizing the diversity of theses resistances is of great importance for breeding wheat cultivars with efficient and durable resistance. While the functional mechanisms underlying these resistance types are not well understood, increasing piece of evidence suggest that fungus stomatal penetration and early establishment in the apoplast are both crucial for the outcome of some interactions between Z. tritici and plants. To validate and extend these previous observations, we conducted quantitative comparative phenotypical and cytological analyses of the infection process corresponding to 22 different interactions between plant species and Z. tritici isolates. These interactions included four major bread wheat Stb genes, four bread wheat accessions with contrasting quantitative resistance, two species resistant to Z. tritici isolates from bread wheat (HSSR) and four plant species resistant to all Z. tritici isolates (NHR). RESULTS: Infiltration of Z. tritici spores into plant leaves allowed the partial bypass of all bread wheat resistances and durum wheat resistance, but not resistances from other plants species. Quantitative comparative cytological analysis showed that in the non-grass plant Nicotiana benthamiana, Z. tritici was stopped before stomatal penetration. By contrast, in all resistant grass plants, Z. tritici was stopped, at least partly, during stomatal penetration. The intensity of this early plant control process varied depending on resistance types, quantitative resistances being the least effective. These analyses also demonstrated that Stb-mediated resistances, HSSR and NHR, but not quantitative resistances, relied on the strong growth inhibition of the few Z. tritici penetrating hyphae at their entry point in the sub-stomatal cavity. CONCLUSIONS: In addition to furnishing a robust quantitative cytological assessment system, our study uncovered three stopping patterns of Z. tritici by plant resistances. Stomatal resistance was found important for most resistances to Z. tritici, independently of its type (Stb, HSSR, NHR). These results provided a basis for the functional analysis of wheat resistance to Z. tritici and its improvement.

Morphological heterogeneity of neurons in the human central amygdaloid nucleus.

The central amygdaloid nucleus (CeA) has an ancient phylogenetic development and functions relevant for animal survival. Local cells receive intrinsic amygdaloidal information that codes emotional stimuli of fear, integrate them, and send cortical and subcortical output projections that prompt rapid visceral and social behavior responses. We aimed to describe the morphology of the neurons that compose the human CeA (N = 8 adult men). Cells within CeA coronal borders were identified using the thionine staining and were further analyzed using the "single-section" Golgi method followed by open-source software procedures for two-dimensional and three-dimensional image reconstructions. Our results evidenced varied neuronal cell body features, number and thickness of primary shafts, dendritic branching patterns, and density and shape of dendritic spines. Based on these criteria, we propose the existence of 12 morphologically different spiny neurons in the human CeA and discuss the variability in the dendritic architecture within cellular types, including likely interneurons. Some dendritic shafts were long and straight, displayed few collaterals, and had planar radiation within the coronal neuropil volume. Most of the sampled neurons showed a few to moderate density of small stubby/wide spines. Long spines (thin and mushroom) were observed occasionally. These novel data address the synaptic processing and plasticity in the human CeA. Our morphological description can be combined with further transcriptomic, immunohistochemical, and electrophysiological/connectional approaches. It serves also to investigate how neurons are altered in neurological and psychiatric disorders with hindered emotional perception, in anxiety, following atrophy in schizophrenia, and along different stages of Alzheimer's disease.

Case report & review: Bilateral NIFTP harboring concomitant HRAS and KRAS mutation: Report of an unusual case and literature review.

Diagnosis and treatment of thyroid disease are affected by the wide range of thyroid cancer subtypes and their varying degrees of aggressiveness. To better describe the indolent nature of thyroid neoplasms previously classified as noninvasive follicular variant of papillary thyroid carcinoma (NI-FVPTC), the Endocrine Pathology Society working group has recently coined the term "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP). The purpose of this nomenclature change is to avoid patients the distress of cancer diagnosis and to decrease the overtreatment of thyroid nodules with a RAS-LIKE molecular profile similar to follicular adenoma. Consequently, the reclassification has a significant impact on thyroid nodule clinical care as well as histopathologic and cytopathologic diagnosis. This paper will focus on a unique case of Bilateral NIFTP harboring concomitant HRAS and KRAS mutation; we will also review the background, molecular features, and clinical implications of NIFTP as well as the factors behind the nomenclature update. It also seemed helpful to emphasize the impact of NIFTP on clinical practice to avoid overtreating nodules that could be safely managed with lobectomy alone. Actually, despite the diagnosis is postsurgery, a comprehensive preoperative evaluation may raise a suspicion of NIFTP and suggest a more careful plan for treatment. Here, we present a unique case of bilateral NIFTP after total thyroidectomy; subsequent molecular analysis revealed that the patient's right nodule harbored an isolated p.(Q61K) HRAS mutation, while the left a p.(Q61K) KRAS mutation. To the best of our knowledge, this is the first case report of this nature. The existence of simultaneous mutations highlights the occurrence of intratumoral heterogeneity (ITH) also in the context of FVPTC, which requires comprehensive investigation. The available information shows that NIFTP, identified in accordance with stringent inclusion and exclusion criteria, exhibits a very latent clinical behavior even in the face of conservative lobectomy, lacking of radioactive iodine therapy. However, it cannot be regarded as a benign lesion because there is a small but significant incidence of adverse events, such as lymph nodes and distant metastases. Currently, NIFTP can only be suspected before surgery: several efforts could be explored to identify key molecular, cytological, and ultrasonographic traits that may be helpful in raising the possibility of NIFTP in the preoperative context. Additionally, our discovery of simultaneous mutations within the same lesion strengthens the evidence of ITH even in FVPTC. Although the extent and biological impact of this phenomenon in NIFTP are still debated, a deeper understanding is essential to ensure appropriate clinical management.

Anal intraepithelial neoplasia screening in women from the largest center for lower genital tract disease in China.

This study aimed to provide comprehensive clinical screening data for anal intraepithelial neoplasia (AIN). This study included 312 patients who underwent high-resolution anoscopy (HRA) examinations between January 1, 2020 and April 15, 2024. Clinical data, including demographic information, clinical history, cytology/high-risk human papilloma virus (hrHPV) results, and HRA records, were analyzed. The median age of all patients was 42 years (interquartile range: 33-52 years). Approximately 26.3% reported a history of VIN2/3+, 13.5% had a history of VaIN2/3+, 29.8% had a history of CIN2/3+, 44.6% had persistent cervical HPV16 infection, and 12.5% had immune suppression. Among the 312 patients, 14.4% were diagnosed with AIN2/3, 25.0% with AIN1 and 60.6% were normal. Anal cytological abnormalities were found in 41.3% of all patients, with a significantly higher rate in AIN2/3 patients than in ≤AIN1, 71.1% versus 36.3%, p < 0.001. The hrHPV positivity rate was 89.7%, with HPV16 being the most prevalent. The complete agreement rate for HRA impressions was 79.5%. Multi-variable analysis revealed immune suppression (odds ratio [OR]: 3.47, 95% confidence interval [CI]: 1.42-8.5) and VIN2/3+ (OR: 2.82, 95% CI: 1.27-6.28) were independent risk factors for AIN2/3. Abnormal cytology results (OR: 3.3, 95% CI: 1.52-7.17) and anal HPV16 infection (OR: 3.2, 95% CI: 1.26-8.12) demonstrated similar ORs for AIN2/3. Early screening for AIN2/3+ is crucial in Chinese women with lower genital tract precancerous and cancerous lesions, particularly in those with VIN2/3+ and immune suppression.

Clinical Significance of Primary Tumor Resection in Perihilar Cholangiocarcinoma with Positive Peritoneal Lavage Cytology.

BACKGROUND: The prognostic impact of positive peritoneal lavage cytology (CY+) in patients with perihilar cholangiocarcinoma (PHC) remains unclear. The present study investigated the clinical significance of primary tumor resection of CY+ PHC. METHODS: We retrospectively evaluated 282 patients who underwent surgery for PHC between September 2002 and March 2022. The patients' clinicopathological characteristics and survival outcomes were compared between the CY negative (CY-) resected (n = 262), CY+ resected (n = 12), and CY+ unresected (n = 8) groups. Univariate and multivariate analyses were performed to identify prognostic factors for overall survival. RESULTS: The expected residual liver volume was significantly higher in the CY+ resected group (61%) than in the CY- resected (47%) and CY+ unresected (37%) groups (p = 0.004 and 0.007, respectively). The CY+ resected group had a higher administration rate of postoperative therapy than the CY- resected group (58% vs. 16%, p = 0.002). Overall survival of the CY+ resected group was similar to that of the CY- resected group (median survival time [MST] 44.5 vs. 44.6, p = 0.404) and was significantly better than that of the CY+ unresected group (MST 44.5 vs. 17.1, p = 0.006). CY positivity was not a prognostic factor according to a multivariate analysis in patients with primary tumor resection. CONCLUSIONS: The CY+ resected group showed better survival than the CY+ unresected group and a similar survival to that of the CY- resected group. Resection of the primary tumor with CY+ PHC may improve the prognosis in selected patients.