Hui Li

Prognostic value of different metastatic sites for patients with FIGO stage IVB endometrial cancer after surgery: A SEER database analysis

AbstractObjectiveThis study aimed to investigate the association between different metastatic sites and survival in endometrial cancer (EC) patients with International Federation of Gynecology and Obstetrics (FIGO) stage IVB disease.MethodsFIGO stage IVB patients with EC were selected from the surveillance, epidemiology, and end results database. Overall survival (OS) and cause‐specific survival (CSS) were analyzed with Kaplan‐Meier analysis and log‐rank tests. Univariate and multivariate Cox proportional hazard models were used to identify the prognostic factors for OS and CSS.ResultsA total of 929 FIGO stage IVB patients with EC were identified. Patients with peritoneum metastasis were associated with significantly better OS and CSS compared to those with organ‐specific metastasis (median OS: 29 vs 19 months, P = .005; median CSS: 47 vs 25 months, P < .001). Moreover, the survival superiority of peritoneum metastasis remained significant when organ‐specific metastasis was further classified into specific single‐organ metastasis. The multivariate analysis also indicated that compared with peritoneum metastasis, bone, brain, and lung metastasis were independent prognostic factors for worse OS. Similarly, distant lymph node, bone, brain, liver, and lung metastasis were associated with worse CSS.ConclusionMetastatic sites affected prognosis in FIGO stage IVB patients with EC. Patients with peritoneum metastasis had significantly better survival outcomes than those with organ‐specific metastasis.

Ultrabright NIR-IIb Fluorescence Quantum Dots for Targeted Imaging-Guided Surgery

Pioneering approaches for precise tumor removal involve fluorescence-guided surgery, while challenges persist, including the low fluorescence contrast observed at tumor boundaries and the potential for excessive damage to normal tissue at the edges. Lead/cadmium sulfide quantum dots (PbS@CdS QDs), boasting high quantum yields (QYs) and vivid fluorescence, have facilitated advancements in the second near-infrared window (NIR-II, 900-1700 nm). However, during fluorescent surgical navigation operations, hydrophilic coatings of these inorganic nanoparticles (NPs) guarantee biosafety; it also comes at the expense of losing a significant portion of QY and NIR-II fluorescence, causing heightened damage to normal tissues caused by cutting edges. Herein, we present hydrophilic core-shell PbS@CdS@PEG NPs with an exceptionally small diameter (∼8 nm) and a brilliant NIR-IIb (1500-1700 nm) emission at approximately 1600 nm. The mPEG-SH (MW: 2000) addresses the hydrophobicity and enhances the biosafety of PbS@CdS QDs.

A phase I dose-finding trial of hyperthermic intraperitoneal docetaxel combined with cisplatin in patients with advanced-stage ovarian cancer

To identify the maximum tolerated dose (MTD) of docetaxel combined with a fixed dose of cisplatin (75 mg/m²) delivered as hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with ovarian cancer. In this phase I trial, a time-to-event Bayesian optimal interval design was used. Docetaxel was given at a starting dose of 60 mg/m² and was increased in 5 mg/m² increments until the MTD was determined or the maximum dose level of 75 mg/m² was reached. The dose-limiting toxicity (DLT) rate was set at 25%, with a total sample size of 30 patients. HIPEC was delivered immediately following debulking surgery at a target temperature of 43°C for 90 minutes. From August 2022 to November 2022, 30 patients were enrolled. Among the patients who received a dose of docetaxel ≤65 mg/m², no DLT was reported. DLTs were observed in one patient who received 70 mg/m² docetaxel (grade 3 anaemia) and in three patients who received 75 mg/m² docetaxel (one case of grade 3 anaemia, one case of grade 3 hepatic impairment and one case of grade 4 thrombocytopenia). Patients treated with docetaxel 75 mg/m² in combination with cisplatin 75 mg/m² had an estimated DLT rate of 25%, which was the closest to the target DLT rate and was therefore chosen as the MTD. Docetaxel, in combination with a fixed dose of cisplatin (75 mg/m²), can be used safely at intraperitoneal doses of 75 mg/m² in ovarian cancer patients who received HIPEC (43°C, 90 minutes) following debulking surgery. ClinicalTrials.gov Identifier: NCT05410483.

Fuzheng Jiedu Decoction Induces Apoptosis and Enhances Cisplatin Efficacy in Ovarian Cancer Cells In Vitro and In Vivo through Inhibiting the PI3K/AKT/mTOR/NF‐κB Signaling Pathway

Objectives. This study is aimed at investigating the anticancer activity of Fuzheng Jiedu decoction (FJD) alone or in combination with cisplatin in ovarian cancer (OC) models, as well as its underlying mechanisms of action. Methods. The anticancer activities of FJD, cisplatin, and the combination of the PI3K inhibitor (LY294002, LY) or activator (IGF‐1) were evaluated in OC cell lines in vitro and in a SKOV3 xenograft mouse model in vivo. The cell proliferation and invasion ability were measured using MTT, EdU, and transwell assays, respectively. The cell apoptosis was examined by flow cytometry and JC‐1 assays. The expression levels of the Bcl‐2 family and the PI3K/AKT/mTOR/NF‐κB pathway‐related proteins were analyzed by Western blot. Results. The in vivo and in vitro studies showed that FJD administration could significantly inhibit cell proliferation and promote cell apoptosis in two OC cell lines SKOV3 and 3AO and partially decreased the tumor volumes and weights. In addition, FJD could significantly downregulate the protein levels of p‐PI3K/PI3K, p‐AKT/AKT, p‐mTOR/mTOR, NF‐κB, p38, and Bcl‐2 and upregulate the Bax, Cyt‐C, and cleaved caspase‐3 in OC tumor tissues and cells. FJD cotreatment increased the efficacy of cisplatin, including inhibiting OC cell proliferation and invasion, promoting cell apoptosis, and inhibiting the PI3K/AKT/mTOR signaling pathway, while this enhancement was suppressed by IGF‐1. Similarly, LY also enhanced the anticancer efficacy of cisplatin. Conclusions. This study indicated that FJD could improve the efficacy of cisplatin by inhibiting the PI3K/AKT/mTOR/NF‐κB signaling pathway. It is suggested that FJD may be a valuable adjuvant drug for the treatment of OC.

Prognostic nomogram and treatment efficacy analysis for vaginal cancer: A SEER database and external validation study

AbstractObjectivesTo analyze the prognosis and treatment decisions for patients with vaginal cancer through a large retrospective cohort study, in order to assist clinicians to evaluate the condition and choose treatment methods.MethodsThis was a retrospective study analyzed with Cox regression, nomogram, and external validation. The Kaplan–Meier curve was used for comparative analysis of various treatment modalities.ResultsA total of 6650 cases of vaginal cancer diagnosed between 2000 and 2018 from the Surveillance, Epidemiology, and End Results database and 106 cases diagnosed between 2006 and 2021 from Fujian Cancer Hospital were identified. Young age, early FIGO (the International Federation of Gynecology and Obstetrics) stage, well‐differentiated, squamous and adenocarcinoma, first primary malignancy, married, undergoing surgery, and chemoradiotherapy were good independent prognostic factors (P < 0.001). The internal and external validation concordance indices were 0.7102 and 0.7785, respectively. The Kaplan–Meier curves indicated that surgery, radiotherapy, and chemotherapy significantly improved survival in patients with vaginal cancer. Forest plots suggest that radiotherapy combined with surgery was superior to radiotherapy alone (P < 0.001).ConclusionWe established a specific nomogram to predict vaginal cancer prognosis. Surgery combined with external beam radiation plus brachytherapy may be the most recommended treatment option.

The First Human Vulvar Intraepithelial Neoplasia Cell Line with Naturally Infected Episomal HPV18 Genome

Persistent infection with high-risk HPV leads to cervical cancers and other anogenital cancers and head and neck carcinomas in both men and women. There is no effective drug fortreating HPV infection and HPV-associated carcinomas, largely due to a lack of models of natural HPV infection and the complexity of the HPV life cycle. There are no available cell lines from vulvar, anal, or penile lesions and cancers in the field. In this study, we established the first human cell line from vulvar intraepithelial neoplasia (VIN) with naturally infected HPV18 by conditional reprogramming (CR) method. Our data demonstrated that VIN cells possessed different biological characteristics and diploid karyotypes from HPV18-positive cancer cells (HeLa). Then, we determined that VIN cells contained episomal HPV18 using approaches including the ratio of HPV E2copy/E7copy, rolling cycle amplification, and sequencing. The VIN cells expressed squamous epithelium-specific markers that are different from HeLa cells, a cervical adenocarcinoma cell line. When cultured under 3D air–liquid interface (ALI) system, we observed the expression of both early and late differentiation markers involucrin and filaggrin. Most importantly, we were able to detect the expression of viral late gene L1 in the cornified layer of ALI 3D culture derived from VIN cells, suggesting quite different HPV genomic status from cancer cells. We also observed progeny viral particles under transmission electron microscopy (TEM) in ALI 3D cultures, confirming the episomal HPV18 genome and active viral life cycle in the new cell line. To our knowledge, this is the first human VIN cell line with naturally infected HPV18 genome and provides a valuable model for HPV biology studies, HPV-associated cancer initiation and progression, and drug-screening platforms.

Administration of Hyperthermic Intraperitoneal Chemotherapy in the General Ward

Ovarian cancer is the most lethal gynecologic malignancy. The majority of patients get diagnosed with advanced disease with peritoneal dissemination.It has been demonstrated that the addition of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to interval debulking surgery can improve the prognosis. The National Comprehensive Cancer Network (NCCN) treatment guideline has recommended HIPEC as a first-line treatment for patients with advanced ovarian cancer. However, the guideline recommended the "Dutch model" of HIPEC, which is limited for routinely being performed in China. So we propose a HIPEC treatment modality, the bedside closed HIPEC in the general ward (C-HIPEC), which is suitable for the clinical characteristics of China. The aim of this study was to evaluate the safety of this model as a way to lay the foundation for subsequent efficacy evaluation and clinical promotion.