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.

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.

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.

Analysis of East Asia subgroup in Study 309/KEYNOTE-775: lenvatinib plus pembrolizumab versus treatment of physician's choice chemotherapy in patients with previously treated advanced or recurrent endometrial cancer.

OBJECTIVE: In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician's choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis. METHODS: Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks (≤35 cycles) or TPC (doxorubicin or paclitaxel). Primary endpoints were PFS per RECIST v1.1 by blinded independent central review and OS. No alpha was assigned for this subgroup analysis. RESULTS: Among 155 East Asian patients (lenvatinib+pembrolizumab, n=77; TPC, n=78), median follow-up time (data cutoff: March 1, 2022) was 34.3 (range, 25.1-43.0) months. Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS (lenvatinib+pembrolizumab vs. TPC) were 0.74 (0.49-1.10) and 0.64 (0.44-0.94) in the mismatch repair proficient (pMMR) and all-comer populations, respectively. HRs (95% CI) for OS were 0.68 (0.45-1.02) and 0.61 (0.41-0.90), respectively. ORRs were 36% with lenvatinib+pembrolizumab and 22% with TPC (pMMR) and 39% and 21%, respectively (all-comers). Treatment-related adverse events occurred in 97% and 96% (grade 3-5, 74% and 72%), respectively. CONCLUSION: Lenvatinib+pembrolizumab provided clinically meaningful benefit with manageable safety compared with TPC, supporting its use in East Asian patients with previously treated advanced/recurrent EC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03517449.

Front-line chemoimmunotherapy for treating epithelial ovarian cancer: Part II promising results of phase 2 study of paclitaxel-carboplatin-oregovomab regimen.

In the Part I, we have discussed the background of CA125 and the development of anti-CA125 monoclonal antibody (MAb) to highlight the potential role of CA125 and anti-CA125 MAb in the management of women with advanced stage epithelial ovarian cancer (EOC). Glycosylation change either by N-link or by O-link of CA125 is supposed to play a role in the modification of immunity. Anti-CA125 MAb, which can be classified as OC 125-like Abs, M11-like Abs, and OV197-like Abs, is often used for diagnosing, screening, monitoring and detecting the mesothelin-related diseases of the abdominal cavity, particular for those women with EOC. Additionally, anti-CA125 MAb also plays a therapeutic role, named as OvaRex MAb-B43.13 (oregovomab), which has also been extensively reviewed in the Part I review article. The main mechanisms include (a) forming CA125 immune complexes to activate the antigen-presenting cells; (b) triggering induction of CA125-specific immune responses, including anti-CA125 Abs against various epitopes and CA125-specific B and T cell responses; and (c) triggering CD4 and CD8 T-cell responses specific for B43.13 to produce specific and non-specific immune response. With success in vitro, in vivo and in primitive studies, phase II study was conducted to test the effectiveness of chemoimmunotherapy (CIT) for the management of EOC patients. In the 97 EOC patients after optimal debulking surgery (residual tumor <1 cm or no gross residual tumor), patients treated with CIT had a dramatical and statistically significant improvement of both progression-free survival (PFS) and overall survival (OS) compared to those treated with chemotherapy alone with a median PFS of 41.8 months versus 12.2 months (hazard ratio [HR] 0.46, 95 % confidence interval [CI] 0.28-0.7) and OS not yet been reached (NE) versus 42.3 months (HR 0.35, 95 % CI 0.16-0.74), respectively. The current review as Part II will explore the possibility of using CIT as front-line therapy in the management of advanced-stage EOC patients after maximal cytoreductive surgery based on the evidence by many phase 2 studies.