Unsuccessful laparoscopic resection of a large pelvic solitary fibrous tumor: A case report.

We present a rare case of a female pelvic solitary fibrous tumor unsuccessfully resected using single-port laparoscopy, requiring conversion to laparotomy. Although the resection was successful, the surgical approach could have been improved. For large tumors, minimally invasive results are possible with flexible choices of equipment and incision position.

Preparation of near-infrared photoacoustic imaging and photothermal treatment agent for cancer using a modifiable acid-triggered molecular platform.

Ratiometric near-infrared fluorescent pH probes with various pKa values were innovatively designed and synthesized based on cyanine with a diamine moiety. The photochemical properties of these probes were thoroughly evaluated. Among the series, IR-PHA exhibited an optimal pKa value of approximately 6.40, closely matching the pH of cancerous tissues. This feature is particularly valuable for real-time pH monitoring in both living cells and living mice. Moreover, when administered intravenously to tumor-bearing mice, IR-PHA demonstrated rapid and significant enhancement of near-infrared fluorescence and photoacoustic signals within the tumor region. This outcome underscores the probe's exceptional capability for dual-modal cancer imaging utilizing near-infrared fluorescence (NIRF) and photoacoustic (PA) modalities. Concurrently, the application of a continuous-wave near-infrared laser efficiently ablated cancer cells in vivo, attributed to the photothermal effect induced by IR-PHA. The results strongly indicate that IR-PHA is well-suited for NIRF/PA dual-modality imaging and photothermal therapy of tumors. This makes it a promising candidate for theranostic applications involving small molecules.

Assessment of Efficacy and Accuracy of Cervical Cytology Screening With Artificial Intelligence Assistive System.

The role of artificial intelligence (AI) in pathology offers many exciting new possibilities for improving patient care. This study contributes to this development by identifying the viability of the AICyte assistive system for cervical screening, and investigating the utility of the system in assisting with workflow and diagnostic capability. In this study, a novel scanner was developed using a Ruiqian WSI-2400, trademarked AICyte assistive system, to create an AI-generated gallery of the most diagnostically relevant images, objects of interest (OOI), and provide categorical assessment, according to Bethesda category, for cervical ThinPrep Pap slides. For validation purposes, 2 pathologists reviewed OOIs from 32,451 cases of ThinPrep Paps independently, and their interpretations were correlated with the original ThinPrep interpretations (OTPI). The analysis was focused on the comparison of reporting rates, correlation between cytological results and histologic follow-up findings, and the assessment of independent AICyte screening utility. Pathologists using the AICyte system had a mean reading time of 55.14 seconds for the first 3000 cases trending down to 12.90 seconds in the last 6000 cases. Overall average reading time was 22.23 seconds per case compared with a manual reading time approximation of 180 seconds. Usage of AICyte compared with OTPI had similar sensitivity (97.89% vs 97.89%) and a statistically significant increase in specificity (16.19% vs 6.77%) for the detection of cervical intraepithelial neoplsia 2 and above lesions. When AICyte was run alone at a 50% negative cutoff value, it was able to read slides with a sensitivity of 99.30% and a specificity of 9.87%. When AICyte was run independently at this cutoff value, no sole case of high-grade squamous intraepithelial lesions/squamous cell carcinoma squamous lesion was missed. AICyte can provide a potential tool to help pathologists in both diagnostic capability and efficiency, which remained reliable compared with the baseline standard. Also unique for AICyte is the development of a negative cutoff value for which AICyte can categorize cases as "not needed for review" to triage cases and lower pathologist workload. This is the largest case number study that pathologists reviewed OOI with an AI-assistive system. The study demonstrates that AI-assistive system can be broadly applied for cervical cancer screening.

Successful pregnancy and delivery after HiPorfin photodynamic therapy for cervical high-grade squamous intraepithelial lesion.

OBJECTIVE: The study analyzed HiPorfin-Photodynamic therapy (PDT) for young women with cervial high-grade squamous intraepithelial lesion (HSIL) and evaluated the impact of PDT on their pregnancy and delivery. METHODS: Retrospective analysis of 4 patients (21-33 years old) were treated with HiPorfin® (2 mg/kg) PDT in 2019-2022. 1 patient suffered from cervical intraepithelial neoplasia (CIN)Ⅱ and 3 patients from CIN Ⅲ. 630 nm laser light irradiated the cervical surface and endocervical canal with light dose of 150 J/cm2 and 100-120 J/cm2 respectively. RESULTS: The median observation time period was 40.5 months. Cure rate, HPV eradication rate and negative conversion rate of cytology were all 100.0 % at 3, 6 and 12 months. All cervical canal lesions completely turned negative. No recurrence occurred during the long-term follow-up period. None of patients suffered from infertility. Three patients delivered vaginally and one delivered by C-section to healthy infants at term. CONCLUSION: HiPorfin® PDT for cervical HSIL was proved to be a safe method without adverse effects on female fertility and allowing these women to have healthy, full-term children.

Metabolic profiles outperform the microbiota in assessing the response of vaginal microenvironments to the changed state of HPV infection.

There is a deficiency in population-based studies investigating the impact of HPV infection on vaginal microenvironment, which influences the risk of persistent HPV infection. This prospective study aimed to unravel the dynamics of vaginal microbiota (VM) and vaginal metabolome in reaction to the changed state of HPV infection. Our results propose that the vaginal metabolome may be a superior indicator to VM when assessing the impact of altered HPV state on the vaginal microenvironment.

Restoration of Pregnancy Function Using a GT/PCL Biofilm in a Rabbit Model of Uterine Injury.

Biomaterial scaffolds have been used successfully to promote the regenerative repair of small endometrial lesions in small rodents, providing partial restoration of gestational function. The use of rabbits in this study allowed us to investigate a larger endometrial tissue defect and myometrial injury model. A gelatin/polycaprolactone (GT/PCL) gradient-layer biofilm was sutured at the defect to guide the reconstruction of the original tissue structure. Twenty-eight days postimplantation, the uterine cavity had been restored to its original morphology, endometrial growth was accompanied by the formation of glands and blood vessels, and the fragmented myofibers of the uterine smooth muscle had begun to resemble the normal structure of the lagomorph uterine cavity, arranging in a circular luminal pattern and a longitudinal serosal pattern. In addition, the repair site supported both embryonic implantation into the placenta and normal embryonic development. Four-dimensional label-free proteomic analysis identified the cell adhesion molecules, phagosome, ferroptosis, rap1 signaling pathways, hematopoietic cell lineage, complement and coagulation cascades, tricarboxylic acid cycle, carbon metabolism, and hypoxia inducible factor (HIF)-1 signaling pathways as important in the endogenous repair process of uterine tissue injury, and acetylation of protein modification sites upregulated these signaling pathways.

Photodynamic therapy with HiPorfin for cervical squamous intraepithelial lesion at childbearing age.

OBJECTIVE: To evaluate the clinical efficacy and safety of HiPorfin® photodynamic therapy (PDT) in the treatment of young women at reproductive age with high-grade squamous intraepithelial lesion (HSIL) of the cervix. METHODS: Prospective study of 41 patients aged 28.8 ± 4.6 years old with cervical intraepithelial neoplasia (CIN) Ⅱ-Ⅲ at Peking University Shenzhen Hospital from March 2019 to January 2023. HiPorfin® (2 mg/kg) was infused intravenously, and 48-72 h later, 630-nm laser irradiation was performed in cervical canal and cervical surface with an irradiation dose of 100-120 J/cm2 and 150 J/cm2 respectively. RESULTS: All 41 patients with no recurrence had been observed at least 12 months follow-up period after PDT. The number of nulliparous women was 30 (30/41, 73.2 %). CIN Ⅱ were 22 cases (22/41,53.7 %) and CIN Ⅲ were 19 cases (19/41,46.3 %). Complete response (CR) was in 95.5 % (21/22) patients with CIN Ⅱ and 78.9 % (15/19) patients with CIN Ⅲ at 6 months follow-up. Meanwhile, CR rate was 100.0 % (22/22) and 84.2 % (16/19) in CIN Ⅱ and CIN Ⅲ group respectively at 12 months. Pre-treatment, all patients (41/41,100 %) were Human papilloma virus (HPV) positive. HPV eradication rate was 63.4 % (26/41), 73.2 % (30/41) and 92.7 % (38/41) at 3, 6 and 12 months after PDT respectively. Before treatment, cytology ≥ atypical squamous cells of undetermined significance (ASCUS) was 78.0 % (32/41). Negative conversion ratio of cytology was 75.0 % (24/32), 90.6 % (29/32) and 100.0 % (32/32) at 3, 6 and 12 months after PDT respectively. There were no serious adverse effects in patients during and after PDT. CONCLUSION: HiPorfin-PDT is a promising and organ-saving approach for cervical HSIL, which also eradicates HPV infection effectively and can be a beacon of hope for the young women with fertility preservation requirement.

AmpFire HPV and ScreenFire RS HPV validation trial.

OBJECTIVES: The human papillomavirus (HPV) screening assays from Atila Biosystems, including the new AmpFire (14 type) and ScreenFire RS (13 type), were subjected to a series of validation tests. METHODS: We used a set of samples from the Chinese Multi-Site Screening Trial (previously tested with cobas 4800 and the next-generation SeqHPV) to satisfy Meijer's criteria for clinical end-point validation. We selected 556 self-collected specimens composed of 273 high-risk HPV (hrHPV) positives and 283 hrHPV negatives on the cobas 4800 and SeqHPV. Of the 273 hrHPV-positive cases, 108 had a disease end point of cervical intraepithelial neoplasia grade 2 (CIN2) or higher, including 47 with cervical intraepithelial neoplasia grade 3 (CIN3+) or higher. We simulated the VALGENT framework for inter- and intralaboratory validation and evaluated the new 4-channel risk-stratified ScreenFire assay in a hierarchal fashion. RESULTS: Both AmpFire and ScreenFire detected 106 (98.1%) of 108 cases with CIN2 or higher, with specificities of 56.7% and 58.1%, respectively. Intralaboratory concordance for 2 runs of AmpFire and ScreenFire was 95.13% and 96.03%, respectively, for overall hrHPV types and 99.10% and 99.46%, respectively, for HPV 16. The interlaboratory concordance of AmpFire and ScreenFire was 93.68% and 94.04% for overall hrHPV and 98.92% and 99.28%, respectively, for HPV 16. Other genotype correlation percentages were similarly high, with κs ranging from 0.86 to 0.94. The ScreenFire RS assay demonstrated excellent "genotype-specific concordance" when evaluated for "clinical guidance" in a hierarchal fashion (noting only the highest risk channel) with both the cobas 4800 and SeqHPV for less than CIN2, CIN2, and CIN3 or higher. CONCLUSIONS: The excellent intra- and interlaboratory reproducibility and the established clinical performance, together with the platforms' simplicity, make these assays particularly applicable to low-resource settings.

AI-assisted system improves the work efficiency of cytologists via excluding cytology-negative slides and accelerating the slide interpretation.

Given the shortage of cytologists, women in low-resource regions had inequitable access to cervical cytology which plays an pivotal role in cervical cancer screening. Emerging studies indicated the potential of AI-assisted system in promoting the implementation of cytology in resource-limited settings. However, there is a deficiency in evaluating the aid of AI in the improvement of cytologists' work efficiency. This study aimed to evaluate the feasibility of AI in excluding cytology-negative slides and improve the efficiency of slide interpretation. Well-annotated slides were included to develop the classification model that was applied to classify slides in the validation group. Nearly 70% of validation slides were reported as negative by the AI system, and none of these slides were diagnosed as high-grade lesions by expert cytologists. With the aid of AI system, the average of interpretation time for each slide decreased from 3 minutes to 30 seconds. These findings suggested the potential of AI-assisted system in accelerating slide interpretation in the large-scale cervical cancer screening.

Outcome of uterine functional structures protection by fertility preservative PUSH surgery in diffuse adenomyosis.

This study reports the outcomes of an innovative fertility-preserving surgery for the treatment of diffuse adenomyosis that is known as a surgery for protection of uterine structure for healing (PUSH Surgery). Developed at Peking University Shenzhen Hospital, PUSH Surgery aims to achieve radical excision of adenomyotic lesions by reconstructing the uterus with overlapping muscle flaps to promote optimal healing of the uterine wall and reduce the risk of scar rupture in subsequent pregnancies. PUSH Surgery was performed on 146 patients with diffuse adenomyosis, with uteri measuring from 8 to 16 gestational weeks and an average volume of 230 ± 150cm³. Regular follow-up was conducted for up to 156 months, revealing a significant reduction in VAS pain scores from 9.4 ± 1.2 before the surgery to 0.3 ± 0.8 and 0.6 ± 1.0 at 1 and 2 years post-surgery, respectively, with a continuous alleviation rate of 96.4% after the operations. Notably, 100% of patients with severe menorrhagia reported normal menstruation volumes within 2 years. Additionally, 31 patients attempted to conceive, resulting in a 58% postoperative pregnancy rate and a 60.0% intrauterine live embryo rate. Operation-related complications occurred in 2.7% of patients, with a 3.6% recurrence rate after more than 2 years of follow-up. Importantly, no cases of uterine rupture or severe complications were observed in the pregnant patients. In conclusion, PUSH Surgery offers a promising approach for the radical excision of adenomyotic lesions, promoting improved tissue healing and significant symptom relief.

Inducing tumor ferroptosis via a pH-responsive NIR-II photothermal agent initiating lysosomal dysfunction.

Ferroptosis is a unique programmed cell death process that was discovered a few years ago and plays an important role in tumor biology and treatment. However, it still remains a challenge to modulate tumor ferroptosis by spatiotemporally controlled cell-intrinsic Fenton chemistry. Herein, a pH activated photothermal sensitizer IR-PE has been designed and synthesized on the basis of cyanine bearing a diamine moiety, which is capable of triggering the lysosomal dysfunction-mediated Fenton pathway under the irradiation of near-infrared light to evoke ferroptosis, thereby improving antitumor efficacy and mitigating systemic side effects.

Diagnostic Potential of Endometrial Cancer DNA from Pipelle, Pap-Brush, and Swab Sampling.

Endometrial cancer (EC) is a major gynecological malignancy with rising morbidity and mortality worldwide. The aim of this study was to explore a safe and readily available sample and a sensitive and effective detection method and its biomarkers for early diagnosis of EC, which is critical for patient prognosis. This study designed a panel targeting variants for EC-related genes, assessed its technical performance by comparing it with whole-exon sequencing, and explored the diagnostic potential of endometrial biopsies using the Pipelle aspirator, cervical samples using the Pap brush, and vaginal specimens using the swab from 38 EC patients and 208 women with risk factors for EC by applying targeted panel sequencing (TPS). TPS produced high-quality data (Q30 > 85% and mapping ratios > 99.35%) and was found to have strong consistency with whole-exome sequencing (WES) in detecting pathogenic mutations (92.11%), calculating homologous recombination deficiency (HRD) scores (r = 0.65), and assessing the microsatellite instability (MSI) status of EC (100%). The sensitivity of TPS in detection of EC is slightly better than that of WES (86.84% vs. 84.21%). Of the three types of samples detected using TPS, endometrial biopsy using the Pipelle aspirator had the highest sensitivity in detection of pathogenic mutations (81.87%) and the best consistency with surgical tumor specimens in MSI (85.16%). About 84% of EC patients contained pathogenic mutations in PIK3CA, PTEN, TP53, ARID1A, CTNNB1, KRAS, and MTOR, suggesting that this small gene set can achieve an excellent pathogenic mutation detection rate in Chinese EC patients. The custom panel combined with ultra-deep sequencing serves as a sensitive method for detecting genetic lesions from endometrial biopsy using the Pipelle aspirator.

CAM-VT: A Weakly supervised cervical cancer nest image identification approach using conjugated attention mechanism and visual transformer.

Cervical cancer is the fourth most common cancer among women, and cytopathological images are often used to screen for this cancer. However, manual examination is very troublesome and the misdiagnosis rate is high. In addition, cervical cancer nest cells are denser and more complex, with high overlap and opacity, increasing the difficulty of identification. The appearance of the computer aided automatic diagnosis system solves this problem. In this paper, a weakly supervised cervical cancer nest image identification approach using Conjugated Attention Mechanism and Visual Transformer (CAM-VT), which can analyze pap slides quickly and accurately. CAM-VT proposes conjugated attention mechanism and visual transformer modules for local and global feature extraction respectively, and then designs an ensemble learning module to further improve the identification capability. In order to determine a reasonable interpretation, comparative experiments are conducted on our datasets. The average accuracy of the validation set of three repeated experiments using CAM-VT framework is 88.92%, which is higher than the optimal result of 22 well-known deep learning models. Moreover, we conduct ablation experiments and extended experiments on Hematoxylin and Eosin stained gastric histopathological image datasets to verify the ability and generalization ability of the framework. Finally, the top 5 and top 10 positive probability values of cervical nests are 97.36% and 96.84%, which have important clinical and practical significance. The experimental results show that the proposed CAM-VT framework has excellent performance in potential cervical cancer nest image identification tasks for practical clinical work.

A case of endocervical adenocarcinoma of the gastric type that was repeatedly misdiagnosed: A case report and literature review.

RATIONALE: Gastric-type endocervical adenocarcinoma (GAS) is non-human papillomavirus-associated cervical cancer and the location of the lesions is in the cervical canal mostly. PATIENT CONCERNS: Vaginal discharge is mistakenly thought to be caused by uterine fibroids. Misdiagnosis leads to disease progression. DIAGNOSES: Magnetic resonance imaging is an auxiliary tool and pathology is the gold standard for the diagnosis. INTERVENTIONS: Surgery and supplementary radiotherapy and chemotherapy ± targeted therapy are the main treatment methods. OUTCOMES: GAS with high malignant degree poor prognosis and insidious development, tends to develop toward the cervical canal and is lack of specific tumor markers, so it is easy to misdiagnosis and missed diagnosis. LESSONS: This case highlights the importance of improving the understanding of GAS. And when patients perform vaginal discharge, cervical canal hypertrophy, and cervical cancer screening negative, clinicians ought to be highly alert to GAS.

Determination of soluble HLA-G serum levels in patients with adenomyosis and uterine fibroids before and after surgery.

Adenomyosis is a benign gynaecological disease caused by the growth of endometrial tissue in the myometrium that affects approximately 30 % of child-bearing-age women. We evaluated the levels of soluble human leukocyte antigen G (sHLA-G) in the serum of patients with adenomyosis before and after treatment. Serum samples of 34 patients with adenomyosis and 31 patients with uterine fibroids were collected before and after the operation and were analysed for sHLA-G levels byELISAassay. The preoperative levels of serum sHLA-G in the adenomyosis group (28.05 ± 2.466 ng/ml) were significantly higher than those in the uterine fibroid group (18.53 ± 1.435 ng/ml) (P < 0.05). Serum sHLA-G levels in the adenomyosis group showed a decreasing trend at different time points after surgery (28.05 ± 14.38 ng/ml, 18.41 ± 8.34 ng/ml, and 14.45 ± 5.77 ng/ml). Adenomyosis patients who underwent total hysterectomy (n = 20) had a more significant decrease in sHLA-G levels in the early postoperative period (2 days post-operative) than those who underwent partial hysterectomy (n = 14). These results suggest that immunologic dysfunctions may be detected in patients with adenomyosis.

A meta-analysis of pregnancy outcomes in the diagnosis of isolated foetal renal parenchyma by prenatal ultrasonography.

BACKGROUND: To effectively circumvent foetal structural abnormalities and serious newborn sequelae, antenatal ultrasound evaluation can support making an early diagnosis for potential prenatal management or the termination of pregnancy. OBJECTIVE: This study systematically evaluated a meta-analysis of different pregnancy outcomes in the diagnosis of isolated foetal renal parenchymal echogenicity (IHEK) by prenatal ultrasonography. METHODS: Two researchers conducted a literature search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The following databases were included in the search: China National Knowledge Infrastructure, Wanfang Medical Network, China Academic Journals Full-text Database, PubMed, Web Of Science and Springer Link; additional library websites were also included, and the search reviewed different pregnancies among patients with IHEK. The outcome indicators were the live birth rate, the incidence of polycystic renal dysplasia and the incidence of pregnancy termination/neonatal death. The meta-analysis was performed using the Stata/SE 12.0 software. RESULTS: A total of 14 studies were included in the meta-analysis (total sample content, 1,115 cases). The combined effect size of prenatal ultrasound diagnosis of pregnancy termination/neonatal mortality in patients with IHEK was 0.289 (confidence interval (CI) 95%; range, 0.102-0.397). The combined effect size of the live birth rate of pregnancy outcomes was 0.742 (CI 95%; range, 0.634-0.850. The combined effect size of the polycystic kidney dysplasia rate was 0.066 (CI 95%; range, 0.030-0.102). The heterogeneity of all three results was > 50%; accordingly, a random-effects model was used. CONCLUSION: The indications for eugenic labour should not be included in a prenatal ultrasound diagnosis of patients with IHEK. In the results of this meta-analysis, the live birth and polycystic dysplasia rates were optimistic in terms of pregnancy outcomes. Therefore, under the condition of excluding other unfavourable factors, it is necessary to A thorough technical inspection is required to make an accurate judgment.

Increased NKG2A+CD8+ T-cell exhaustion in patients with adenomyosis.

Immune dysregulation has long been proposed to be associated with adenomyosis, but the underlying mediators and mechanisms remain largely unexplored. Here, we used flow cytometry to investigate the alterations in immune cell subsets in adenomyotic uteri and analyze the phenotype and function of abnormal immune cells. We found that an increase in cluster of differentiation (CD)8+ T-cell number was the predominant alteration in ectopic lesions in patients with adenomyosis and was significantly associated with the severity of adenomyosis. Importantly, we identified an exhausted natural killer group protein 2A (NKG2A)+CD8+ T-cell subset that was associated with the severity of adenomyosis and found that the number of these cells was significantly increased in the eutopic endometrium and ectopic lesions. In addition, the increases in the expression of NKG2A ligand histocompatibility leucocyte antigen E and interleukin-15 in glandular epithelial cells in the adenomyotic microenvironment might contribute to CD8+ T-cell exhaustion by promoting NKG2A expression on CD8+ T cells or inhibiting the effector function of these cells. In conclusion, our data revealed a previously unrecognized role for NKG2A+CD8+ T-cell exhaustion in the pathogenesis of adenomyosis, indicating that therapeutic interventions designed to target and reinvigorate exhausted CD8+ T cells may be beneficial for patients with adenomyosis.

A Polyoxometalate-Encapsulated Metal-Organic Framework Nanoplatform for Synergistic Photothermal-Chemotherapy and Anti-Inflammation of Ovarian Cancer.

Photothermal therapy (PTT), as a noninvasive and local treatment, has emerged as a promising anti-tumor strategy with minimal damage to normal tissue under spatiotemporally controllable irradiation. However, the necrosis of cancer cells during PTT will induce an inflammatory reaction, which may motivate tumor regeneration and resistance to therapy. In this study, polyoxometalates and a chloroquine diphosphate (CQ) co-loaded metal-organic framework nanoplatform with hyaluronic acid coating was constructed for efficient ovarian cancer therapy and anti-inflammation. Our results demonstrated that this nanoplatform not only displayed considerable photothermal therapeutic capacity under 808 nm near-infrared laser, but also had an impressive anti-inflammatory capacity by scavenging reactive oxygen species in the tumor microenvironment. CQ with pH dependence was used for the deacidification of lysosomes and the inhibition of autophagy, cutting off a self-protection pathway induced by cell necrosis-autophagy, and achieving the synergistic treatment of tumors. Therefore, we combined the excellent properties of these materials to synthesize a nanoplatform and explored its therapeutic effects in various aspects. This work provides a promising novel prospect for PTT/anti-inflammation/anti-autophagy combinations for efficient ovarian cancer treatment through the fine tuning of material design.