Bevacizumab is associated with a higher gastrointestinal/genitourinary fistula or perforation risk in cervical cancer patients undergoing pelvic radiotherapy.

BACKGROUND: Bevacizumab serves as an effective treatment in cervical cancer patients with metastatic, recurrent, or advanced disease. However, gastrointestinal (GI)/genitourinary (GU) toxicities have been observed after bevacizumab treatment. Radiotherapy (RT) is the mainstay of treatment of cervical cancer. OBJECTIVES: To investigate the risk of GI/GU toxicities with bevacizumab plus RT compared with RT alone in cervical cancer patients. SEARCH STRATEGY: In this meta-analysis, PubMed, Embase, Web of Science, and Cochrane databases were searched from inception to September 25, 2022. SELECTION CRITERIA: Cohort studies evaluating the association between bevacizumab and GI/GU fistula or perforation in irradiated metastatic, recurrent, or advanced cervical cancer patients. DATA COLLECTION AND ANALYSIS: Results are expressed as odds ratios (OR) with 95% confidence intervals (CI). The inconsistency test (I2) was used to assess heterogeneity. Egger's regression test with a two-tailed P value was used to evaluate publication bias. MAIN RESULTS: Four cohort studies met the inclusion criteria with a total of 597 women included. There was a significant association between GI fistula/perforation and GU fistula/perforation in irradiated cervical cancer patients receiving bevacizumab (OR 4.03 [95% CI: 1.76-9.20] and OR 4.71 [95% CI: 1.51-14.70], respectively). CONCLUSIONS: The bevacizumab-containing regimen was associated with an increased risk of GI or GU toxicities in cervical cancer individuals undergoing pelvic RT. These results suggest the bevacizumab-associated benefits and risk should be better weighted to reach an optimal treatment strategy. Further investigation on optimal dosage and timing of bevacizumab and RT is vital to minimize the adverse events and maximize the benefits.

Cervical cancer: Part I human papilloma virus vaccination in Taiwan.

A significant decline in both incidence and prevalence of cervical cancers after widespread-introducing cervical screening strategy by Papanicolau test (Pap test) has been found in the world, but cervical cancer is still one of the most common female cancers, reporting the fourth prevalence and also one of the leading causes to result in main women-associated morbidity and mortality, particularly for those women living in low- and middle-income countries. Cervical cancer is one of the most important health concerns directly destroying the global health-care system, partly because of not only increasing the disability either secondary to diseases themselves of victims or mediated by treatment-related adverse events to the survivors but also acting as a leading cause of death of diseased patients worldwide, alarming the urgent need to do something to minimize the catastrophic diseases-related heavy socioeconomic burden. It is fortunate that cervical cancer is a preventable disease, based on its strong association with human papillomavirus (HPV) infection (more than 95%), particularly for those high-risk HPV (HR-HPV) and its high possibility by detecting HPV infection before the development of cervical cancer as well as an effective prevention by HPV vaccination. That is why WHO (World Health Organization) considers cervical cancer as a public problem and attempts to accelerate the elimination of cervical cancer program by three-pillar approach (90:70:90% targets), including (1) 90% of girls are fully vaccinated with HPV vaccine by 15 years of age; (2) 70% of women are screened with a high-performance test by 35 and 45 years of age and precancerous lesions are treated early; and (3) 90% of women identified with cervical diseases receive appropriate and adequate treatment. Herein, this review focuses on the HPV vaccination as Part I, including global recommendations and Taiwan government's policy for HPV vaccination.

Efficacy and safety of fezolinetant for moderate to severe vasomotor symptoms associated with menopause among women in East Asia: a phase 3 randomized study (MOONLIGHT I).

OBJECTIVE: To evaluate the efficacy and safety of fezolinetant for moderate to severe vasomotor symptoms (VMS) associated with menopause in East Asian women. METHODS: In this phase 3, randomized, double-blind study, postmenopausal women with moderate to severe VMS (minimum average frequency in the 10 days before randomization, ≥7/day or 50/week) received fezolinetant 30 mg/day or placebo (weeks 1-12), followed by an open-label extension phase with fezolinetant 30 mg/day (weeks 13-24). The co-primary endpoints were the mean changes in the daily frequency and severity of VMS at weeks 4 and 12. RESULTS: Among 301 participants, the difference in the least squares mean change (95% confidence interval) from baseline in the daily frequency of moderate to severe VMS versus placebo was -0.65 (-1.41 to 0.12) at week 4 and -0.55 (-1.35 to 0.26) at week 12. The differences in the least squares mean change from baseline in the VMS severity score versus placebo were -0.06 (-0.14 to 0.03) and -0.13 (-0.27 to 0.01) at weeks 4 and 12, respectively. Serious adverse events occurred in 0.7% of participants receiving fezolinetant in weeks 1 to 12, compared with 1.3% of those receiving placebo. CONCLUSIONS: Fezolinetant was generally safe but did not reduce the frequency or severity of VMS versus placebo in postmenopausal women in this study.ClinicalTrials.Gov Identifier: NCT04234204.

Intrauterine adhesion.

Intrauterine adhesions (IUA) occurred in the reproductive-age women are a big economic and health problem, resulting in severe impairment of social, psychological and physical function of the female genital organs. IUA-related symptoms or signs are varied greatly from free of symptoms or ambiguous symptoms (an incidental finding during the intervention) to ceased menstruation and loss of fecundability. The underlying pathophysiology is not completely understood, but intrauterine damage with broken basal layers of the endometrium formatting scar tissues or fibrosis in the endometrium with subsequently causing partial or complete occlusion of the uterine cavity may be a well-accepted hypothesis. Previously, infection is the most common cause to develop IUA, but now, intrauterine surgery may be a critical cause contributing to the majority of cases of IUA. In the current review, update information about the etiology, epidemiology, pathophysiology, sequelae and prevention of IUA will be renewed. We emphasize the importance of awareness of IUA, and primary prevention should be considered in the routine clinical practice if intrauterine surgery has been applied, based on uncertainty of ideal treatment for the established IUA and unpredictable outcomes after IUA treatment. So far, evidence supports that hyaluronic acid with/without other strategy is the most valuable and effective method to reduce the formation and re-formation of IUA as well as to achieve the best fertility outcome.

Facilitating safe and sustained submucosal lift through an endoscopically injectable shear-thinning carboxymethyl starch sodium hydrogel.

Traditional submucosal filling materials frequently show insufficient lifting height and duration during clinical procedures. Here, the anionic polysaccharide polymer sodium carboxymethyl starch and cationic Laponite to prepare a hydrogel with excellent shear-thinning ability through physical cross-linking, so that it can achieve continuous improvement of the mucosal cushion through endoscopic injection. The results showed that the hydrogel (56.54 kPa) had a lower injection pressure compared to MucoUp (68.56 kPa). The height of submucosal lifting height produced by hydrogel was higher than MucoUp, and the height maintenance ability after 2 h was 3.20 times that of MucoUp. At the same time, the hydrogel also showed satisfactory degradability and biosafety, completely degrading within 200 h. The hemolysis rate is as low as 0.76 %, and the cell survival rate > 80 %. Subcutaneous implantation experiments confirmed that the hydrogel showed no obvious systemic toxicity. Animal experiments clearly demonstrated the in vivo feasibility of using hydrogels for submucosal uplift. Furthermore, successful endoscopic submucosal dissection was executed on a live pig stomach, affirming the capacity of hydrogel to safely and effectively facilitate submucosal dissection and mitigate adverse events, such as bleeding. These results indicate that shear-thinning hydrogels have a wide range applications as submucosal injection materials.

Unveiling intratumoral microbiota: An emerging force for colorectal cancer diagnosis and therapy.

Microbes, including bacteria, viruses, fungi, and other eukaryotic organisms, are commonly present in multiple organs of the human body and contribute significantly to both physiological and pathological processes. Nowadays, the development of sequencing technology has revealed the presence and composition of the intratumoral microbiota, which includes Fusobacterium, Bifidobacteria, and Bacteroides, and has shed light on the significant involvement in the progression of colorectal cancer (CRC). Here, we summarized the current understanding of the intratumoral microbiota in CRC and outline the potential translational and clinical applications in the diagnosis, prevention, and treatment of CRC. We focused on reviewing the development of microbial therapies targeting the intratumoral microbiota to improve the efficacy and safety of chemotherapy and immunotherapy for CRC and to identify biomarkers for the diagnosis and prognosis of CRC. Finally, we emphasized the obstacles and potential solutions to translating the knowledge of the intratumoral microbiota into clinical practice.

A convenient protonated strategy for constructing nanodrugs from hydrophobic drug-inhibitor conjugates to reverse tumor multidrug resistance.

Combination therapy has proven effective in counteracting tumor multidrug resistance (MDR). However, the pharmacokinetic differences among various drugs and inherent water insolubility for most small molecule agents greatly hinder their synergistic effects, which makes the delivery of drugs for combination therapy in vivo a key problem. Herein, we propose a protonated strategy to transform a water-insoluble small molecule drug-inhibitor conjugate into an amphiphilic one, which then self-assembles into nanoparticles for co-delivery in vivo to overcome tumor MDR. Specifically, paclitaxel (PTX) is first coupled with a third-generation P-glycoprotein (P-gp) inhibitor zosuquidar (Zos) through a glutathione (GSH)-responsive disulfide bond to produce a hydrophobic drug-inhibitor conjugate (PTX-ss-Zos). Subsequently treated with hydrochloric acid ethanol solution (HCl/EtOH), PTX-ss-Zos is transformed into the amphiphilic protonated precursor and then forms nanoparticles (PTX-ss-Zos@HCl NPs) in water by molecular self-assembly. PTX-ss-Zos@HCl NPs can be administered intravenously and accumulated specifically at tumor sites. Once internalized by cancer cells, PTX-ss-Zos@HCl NPs can be degraded under the overexpressed GSH to release PTX and Zos simultaneously, which synergistically reverse tumor MDR and inhibit tumor growth. This offers a promising strategy to develop small molecule self-assembled nanoagents to reverse tumor MDR in combination therapy.

Recent advances of ultrasound-responsive nanosystems in tumor immunotherapy.

Immunotherapy has revolutionized cancer treatment by boosting the immune system and preventing disease escape mechanisms. Despite its potential, challenges like limited response rates and adverse immune effects impede its widespread clinical adoption. Ultrasound (US), known for its safety and effectiveness in tumor diagnosis and therapy, has been shown to significantly enhance immunotherapy when used with nanosystems. High-intensity focused ultrasound (HIFU) can obliterate tumor cells and elicit immune reactions through the creation of immunogenic debris. Low-intensity focused ultrasound (LIFU) bolsters tumor immunosuppression and mitigates metastasis risk by concentrating dendritic cells. Ultrasonic cavitation (UC) produces microbubbles that can transport immune enhancers directly, thus strengthening the immune response and therapeutic impact. Sonodynamic therapy (SDT) merges nanotechnology with immunotherapy, using specialized sonosensitizers to kill cancer cells and stimulate immune responses, increasing treatment success. This review discusses the integration of ultrasound-responsive nanosystems in tumor immunotherapy, exploring future opportunities and current hurdles.