Patients with non-germinal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL) often exhibit suboptimal responses to standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy.

This multicenter, phase II study evaluated the safety and efficacy of zanubrutinib, lenalidomide, and R-CHOP (ZR2-CHOP) in newly diagnosed non-GCB DLBCL. Patients received oral zanubrutinib (160 mg twice daily), lenalidomide (25 mg once daily on Days 1-7), and standard R-CHOP every 21 days for up to six cycles.

A total of 34 patients were enrolled. The median age was 55 years, with 29.4% over 60 years. Double-expressor lymphoma (DEL) was present in 64.7%, and 39.3% were classified as the MCD genetic subtype. The best overall response rate was 100%. Complete response (CR) was achieved in 70.6% of patients at mid-treatment and 94.1% at end-of-treatment. With a median follow-up of 28 months, the 2-year progression-free survival (PFS) rate was 84.8%, and the 2-year overall survival (OS) rate was 96.8%. In this small cohort, PFS benefit appeared consistent across high-risk subgroups, including those with DEL and MCD subtypes. Plasma ctDNA negativity was achieved in 84% (21/25) of evaluable patients during treatment. Grade 3-4 adverse events occurred in 67.6% of patients, primarily hematologic toxicities.

ZR2-CHOP demonstrated promising efficacy and manageable toxicity in newly diagnosed non-GCB DLBCL.

ClinicalTrials.gov Identifier: NCT05200312 (registered January 20, 2022).

Combination immunotherapies, such as pembrolizumab plus lenvatinib (PL), are commonly used in treatment for unresectable hepatocellular carcinoma (uHCC). However, it remains challenging to predict which patients will benefit from this therapy. This study aimed to address this issue by comparing immune cell profiles (ICPs) between uHCC patients with objective response (responders, R) and those with tumor progression (non-responders, NR) following PL therapy, and to identify the key contributors to ICPs.

We prospectively enrolled 51 uHCC patients between July 2019 and July 2023. Peripheral blood samples were collected prior to initiating PL therapy, and ICPs were analyzed according to tumor response according to RECIST 1.1 criteria. A machine learning (ML) model was developed to differentiate R from NR using baseline ICP data.

16 patients achieved objective tumor responses, while 11 experienced disease progression following PL therapy. Responders exhibited higher levels of total T cells, CD8 T cells, and PD-1⁺ subpopulations of CD4 T cells, CD8 T cells, and NK cells. In contrast, NR had higher proportions of PD-L1⁺ monocytes. The trained ICP-based ML model accurately discriminated between the two groups, achieving 100% sensitivity and 66.7% specificity, with CD8 T cells, PD-1⁺ CD8 NK cells, and PD-L1⁺ monocytes contributing significantly to the classification.

This study recognized distinct ICPs between uHCC patients with and without tumor response to PL therapy and identified key contributing immune subpopulations. These findings provide a foundation for developing predictive tools for clinical outcomes before initiating combination immunotherapy.

Cancer survivors in Germany face considerable challenges related to the late and long-term effects of treatment and a lack of post-treatment support. Despite an increasing number of cancer survivors, existing healthcare systems are insufficiently adapted to meet their ongoing needs, particularly for long-term survivors who may experience physical, emotional, and socio-economic hardships. This study aims to address the knowledge gaps in the care situation of long-term cancer survivors, focusing on their experiences and the barriers they face in accessing care.

This study protocol outlines the methodology for a quantitative survey involving up to 3,300 long-term cancer survivors across various cancer types in Germany. The survey assesses their experiences with cancer care, focusing on diet, exercise, mental health, sleep, cognition, overall health-related quality of life, and somatic late effects. Special attention is given to survivors from diverse socio-demographic backgrounds, including those with a migration history, in order to explore the unique challenges they face.

The results of the study will contribute to the development of needs-based care recommendations for cancer survivors, particularly those in potentially vulnerable groups. The findings will inform the design of more inclusive care strategies and interventions, leading to better long-term health outcomes for cancer survivors in Germany.

German Clinical Trials Register: DRKS00032146, registered on 03/12/2024.

Urinary frequency and vulvovaginitis are common diseases in girls, but there is insufficient emphasis on the relationship between them. This study aimed to investigate the effect of treatment for vulvovaginitis on urinary frequency in girls with urinary frequency and vulvovaginitis.

We conducted a retrospective analysis of clinical data of 102 girls with urinary frequency and vulvovaginitis who visited the Urologic Surgery Clinic of our hospital between January 1, 2022 and December 31, 2023. After one week of treatment for vulvovaginitis we evaluated the improvement of urinary frequency symptoms. If there was a significant improvement or cure of urinary frequency it was considered that symptoms were related. If there was no significant improvement in urinary frequency, it was considered that symptoms were unrelated. Patients were grouped by their response to treatment. Clinical data were compared between the two groups.

Among the 452 girls with urinary frequency seen in the outpatient clinic, 102 (22.6%) had vulvovaginitis, and all showed daytime urinary frequency. Related group: 81 (79.4%) age 2-9 years, mean age (4.321±1.738), unrelated group: 21 (20.6%) age 2-9 years, mean age (4.905±1.947), there was no significant difference in age between the two groups. The children in the unrelated group had a statistically significant longer duration of urinary frequency (9.286±7.747 days) on first visit than girls in the related group (4.284±2.812 days) (P<0.05). The incidence of enuresis, constipation, and voiding with vulvar pain in the unrelated group (14.3%, 33.3%, and 38.1%) were higher than in the related group (0%, 9.9%, and 6.2%), with a statistically significant difference, all P<0.05. The incidence of urinary incontinence, vulvar secretions, and vulvar pruritus in the related group (0%, 12.3%, and 7.4%) didn't vary significantly from the unrelated group (4.8%, 19.0%, and 9.5%), all P＞0.05. Girls with longer urinary frequency duration (OR=1.25, P=0.004), constipation (OR=4.295, P=0.046) and voiding with vulvar pain (OR=9.772, P=0.002) were more likely to have no improvement in urinary frequency after treatment of vulvovaginitis.

Vulvovaginitis is a common cause of urinary frequency. Girls with urinary frequency combined with vulvovaginitis should first be treated for vulvovaginitis. For children with a long course of illness or accompanying constipation, and voiding with vulvar pain, treatment for urinary frequency should be started simultaneously with vulvovaginitis treatment, as well as treatment for constipation.

Human papillomavirus (HPV) infection is a significant public health concern globally, with its burden increasing in regions with limited access to screening and preventive measures. Understanding how HPV affects different populations is crucial, genetic background, behavioral factors, sexual health practices, co-infections, and access to screening and vaccination services significantly influence disease dynamics, prevalence of high-risk genotypes, and progression to malignancies such as cervical cancer. Such variations underscore the importance of region-specific epidemiological studies and serve as key predictors which can impact the well-being of the population. The study aims to investigate the prevalence and burden of HPV and its association with different risk factors among the indigenous Mizo women of Mizoram, Northeast India.

This cross- sectional study was conducted among 1018 women age (20-73 years) from November 2023 to 2024 from different districts in Mizoram. Cervical swabs were collected in VTM after obtaining consent from the patients as well as the demographic and clinical data via a questionnaire. DNA-based HPV genotyping and Pap smear analysis were performed. Statistical analysis was performed by using SPSS version 22.0 software to determine the association between HPV and the risk factors.

Out of the 1018 participants, findings revealed a 14.9% overall prevalence of HPV infection, with most participants being from the district capital, Aizawl (78.7%). Age group 51-60 years age group had a notable proportion of HPV-positive individuals (11.5%), they exhibited significantly lower odds of HPV infection compared to younger age groups (OR = 0.155, 95% CI: 0.038-0.632; p = 0.009). Most participants were married (93.3%) with 78.5% being housewives. Among different occupations, participants employed in government sectors have a higher odds ratio 1.898 of HPV infection suggesting potential occupational or lifestyle-related influence on infection risk. Key lifestyle factors such as betel nut consumption and early sexual debut are associated with increased infection risk. Cervicitis, chronic pelvic pain and multiple pregnancies were significant clinical indicators. Ingestion of oral contraceptives were less likely to be HPV positive than were those who did not ingest them (OR: 0.604, Cl: 0.399-0.915; p = 0.017). Pap smear results revealed associations with high-grade squamous intraepithelial lesions (p = 0.025). Genotypes HPV-16 (26.97%) and HPV-18 (17.11%) were the most prevalent genotypes. Approximately 23.4% of the patients presented with multiple genotype infections.

This study underscores the importance of tailored public health strategies for high-risk regions such as Mizoram. These include promoting HPV vaccination, enhancing screening programs, and addressing sociocultural practices contributing to infection risk. While the cross-sectional design, female-only participation, and lack of follow-up limit causal interpretation and generalizability. Comprehensive interventions and awareness campaigns are crucial to mitigate the HPV burden and reduce the incidence of cervical cancer in this unique sociodemographic context.

Lenvatinib resistance significantly limits treatment efficacy in hepatocellular carcinoma (HCC), yet the underlying mechanisms remain poorly understood. This study investigates the role of EZH2 in mediating lenvatinib resistance through ferroptosis regulation, aiming to identify novel therapeutic targets for overcoming drug resistance in HCC.

EZH2 expression patterns were analyzed using TCGA datasets and validated in clinical HCC samples through RT-qPCR. Lenvatinib-resistant HCC cell lines were established to examine EZH2's functional role. The impact of EZH2 on ferroptosis was evaluated by measuring cell proliferation, reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) levels. Mechanistic investigations were performed using EZH2 knockdown, ACSL1 expression analysis, and H3K27me3 modification assays. The therapeutic potential of EZH2 inhibition was further assessed in xenograft models.

EZH2 was significantly overexpressed in HCC tissues and correlated with poor patient survival. Resistant cell models demonstrated EZH2-mediated suppression of ferroptosis through ACSL1 downregulation via H3K27me3, evidenced by altered ROS, MDA and GSH levels. Genetic inhibition of EZH2 restored lenvatinib sensitivity by upregulating ACSL1 and promoting ferroptosis. In vivo studies confirmed that EZH2 targeting enhanced lenvatinib's antitumor effects in resistant HCC models.

Our findings establish EZH2 as a critical regulator of lenvatinib resistance in HCC through ACSL1-mediated ferroptosis suppression. The EZH2-H3K27me3-ACSL1 axis represents a promising therapeutic target for overcoming drug resistance, offering new strategies to improve HCC treatment outcomes.

Medullary thyroid carcinoma (MTC) is a rare malignancy with limited treatment options in the metastatic setting. While peptide receptor radionuclide therapy (PRRT) with [¹⁷⁷Lu]Lu-DOTA-TATE has been well established in gastroenteropancreatic neuroendocrine tumors, its clinical utility in MTC remains under investigation.

We retrospectively analyzed 18 patients with advanced, somatostatin receptor-positive MTC treated with [¹⁷⁷Lu]Lu-DOTA-TATE. Treatment decisions-including in patients with low somatostatin receptor (SSTR) expression or first-line PRRT indication-were made by a multidisciplinary tumor board. Anatomical response was assessed using RECIST 1.1 on [⁶⁸Ga]Ga-DOTA-TATE PET/CT after two cycles. Biochemical and clinical outcomes were also recorded. Progression-free survival (PFS) was evaluated using Kaplan-Meier and Cox regression.

Median PFS was 37.0 months. Radiologic disease control -defined as partial response (PR) or stable disease (SD) -was achieved in 78%, and biochemical response (≥ 50% decrease in calcitonin) in 44% of patients. Patients with bone metastases had significantly shorter PFS (24.6 vs. 47.0 months, p = 0.027). Longer PFS was also observed in those receiving higher cumulative dose, those with larger solitary tumors, and those treated in the first-line setting, although these trends did not reach statistical significance. Discordance between anatomical and biochemical response was observed in 50% of cases, highlighting limitations of calcitonin-based monitoring.

PRRT with [¹⁷⁷Lu]Lu-DOTA-TATE is a well-tolerated treatment option for selected patients with advanced MTC, including those receiving first-line therapy and those with low SSTR expression. In our limited cohort, bone metastases were associated with shorter PFS, and discordant imaging/biochemical responses are common. Functional imaging-guided selection and individualized response assessment are essential for optimal management.

The exact value of cluster of differentiation 47 (CD47), known as the "don't eat me" signal, in colorectal cancer (CRC) has not been clearly revealed. Thus, we investigated the impact of its expression on the overall survival (OS) of CRC patients who underwent colectomy.

Ninety-eight CRC patients were included. The patient population was grouped into two categories based on the median value of CD47 expression examined with immunohistochemistry: negative (< median) and positive (≥ median). The estimation of OS was executed with the Kaplan-Meier method, and the difference in prognostic groups was tested with the log-rank test. The association of CD47 with OS was examined with univariate and multivariate Cox regression models.

CD47 expression was recorded in 56.1% of CRC patients. Among the clinicopathological variables, the only significant difference between the prognostic groups was the presence of lymph node involvement (p = 0.005). The OS of patients with CD47 expression was lower than those with no CD47 expression (39.3 months vs. not reached, p = 0.001, respectively). Additionally, in metastatic CRC patients treated with biologic agents, patients with CD47 expression had numerically inferior OS times than those without CD47 expression (37 months vs. 58.5 months, p = 0.05, respectively). Our multivariate analysis showed that CD47 was an independent prognostic factor associated with OS in this cohort (HR: 2.142, p = 0.006).

Our study suggests that CD47 may serve as a potential prognostic marker and a promising therapeutic target for anti-CD47-based treatments in CRC.

The National Health System is responsible for 8-10% of total greenhouse gas emissions. Operating rooms are responsible for 60-70% of all hospital waste. Over the last 30 years abdominal surgery transcended from a laparoscopic approach toward a robot-assisted approach. The role of robot-assisted laparoscopic surgery is still debated in some procedures, such as colorectal surgery. The studies available in scientific literature comparing laparoscopic and robot-assisted left hemicolectomy are focused on clinical outcomes. The environmental sustainability of these procedures remains largely unexplored, representing a key area that our study seeks to investigate.

In this pilot study consecutive patients scheduled for a minimally invasive left hemicolectomy for diverticular disease or cancer were recruited and randomly assigned 1:1 to the laparoscopic or robotic groups. The "Green Team" supported the operating room staff in separate waste collection during the surgical procedures. Primary end point was CO₂ consumption and secondary endpoints the specific mass of the most important waste stream.

Ten patients were enrolled. Robot-assisted left hemicolectomy required more CO₂ consumption in liters to maintain pneumoperitoneum (p = 0.03) compared with laparoscopic left hemicolectomy and required a longer operation time (p = 0.04). In total, the robot and laparoscopic approaches produced a total of 74.5 and 54 kg of plastic, non-woven fabric (TNT), unsorted waste bins, and biohazardous waste combined, which cost €92 and €71 to dispose of.

Robot-assisted left hemicolectomy seems to have a greater environmental impact compared with laparoscopic left hemicolectomy in terms of both CO₂ emissions and waste production. Given the growing focus on operating room sustainability, further studies are needed to compare laparoscopic and robotic techniques to inform surgical decisions.

To compare the real-world efficacy and safety of bispecific antibodies (BsAbs, PD-1/CTLA-4) versus PD-1 inhibitors (ICIs), each combined with platinum-based chemotherapy ± bevacizumab, as first-line treatment for persistent, recurrent, or metastatic cervical cancer (p/r/m CC).

In our single-center retrospective matched cohort study, 121 patients treated between January 2021 and February 2025 were recruited. They were divided into two groups: the bispecific antibody combination group and the PD-1 inhibitor combination group. After propensity score matching (PSM, 1:1, caliper = 0.2), early response to treatment, survival outcomes, and treatment-related adverse events (TRAEs) were assessed. Subgroup analyses, prognostic analyses, and sensitivity analyses were also conducted.

After PSM, 86 patients were analyzed (43 per group). The median follow-up duration was 20.8 months (interquartile range [IQR], 12.1-27.1 months). Early response assessment after two treatment cycles showed no significant difference between the BsAb-Combo and PD-1i-Combo groups (ORR 60.5% vs. 51.2%, p = 0.385; DCR 95.3% vs. 97.7%, p = 1.000). The mPFS was 20.2 months (95% CI, 18.6-not reached) in the BsAb-Combo group and 27.2 months (95% CI, 12.6-not reached) in the PD-1i-Combo group (HR = 0.88, 95% CI 0.44-1.75; log-rank p = 0.708). Grade 3-5 decreased white blood cell count was more frequent with PD-1i-Combo (37.2% vs. 9.3%, p = 0.002), whereas all-grade diarrhea was more common with BsAb-Combo (46.5% vs. 25.6%, p = 0.043). Subgroup analyses suggested that persistent/recurrent with distant metastases tended to benefit more from BsAb-Combo. In multivariate Cox models, ECOG Performance Status 2, lung metastasis, and ≥ 1-year maintenance therapy were independent prognostic factors for PFS.

BsAbs (PD-1/CTLA-4) combined with platinum-based chemotherapy ± bevacizumab demonstrated comparable efficacy and safety to PD-1 inhibitors and showed a favorable hazard-ratio trend. Hypothesis-generating signals observed in select subgroups, such as those with persistent or recurrent disease with distant metastases, warrant confirmation in prospective studies with extended follow-up.