BACKGROUND:The special physiological changes during pregnancy pose a huge challenge to the diagnosis of cervical cancer in pregnancy (CCIP). However, due to the poor prognosis of advanced-stage CCIP, there is currently no consensus or guideline for diagnosis and treatment. CASE SUMMARY:In this case report, we presented the case of a 30-year-old woman at 30 weeks of gestation who presented with irregular vaginal bleeding and was admitted to a local hospital at 35 weeks of gestation with a sudden gush of fluid and underwent a C-section. During the surgery, a rotten fish-like solid mass in the lower segment of the posterior wall of the uterus was excised for biopsy. The patient was referred to our hospital because she experienced heavy vaginal bleeding 13 days after one chemotherapy session. The solid mass was initially misdiagnosed as uterine clear-cell carcinoma at local hospital but later confirmed as cervical adenosquamous carcinoma by a multidisciplinary team. Three months posttreatment, she succumbed to multiple tumor metastases. The infant was healthy at the latest 2-year follow-up. CONCLUSION:Obstetricians should expand differential diagnoses when obstetric factors cannot explain symptoms of persistent vaginal bleeding during pregnancy. Atypical and insidious clinical presentations are often concealed by physiological changes during pregnancy, which may increase the difficulty of diagnosis and result in misdiagnosis.

BACKGROUND:Floating-harbor syndrome (FHS) is a rare genetic disorder caused by pathogenic variants in the SRCAP gene. Most individuals with FHS have short stature, delayed speech and language development, and dysmorphic facial features. However, the patients with FHS are not easy to diagnose due to the overlap of clinical phenotypes with other disorders. CASE SUMMARY:We reported a 10-year-old boy who presented with severe short stature, developmental delay and distinctive facial features. Exome sequencing was provided for the proband and his parents. We identified a novel frameshift variant c.7235delinsGT (p.Thr2412fs) in SRCAP gene, and the variant was further validated by Sanger sequencing. The mother of the proband was referred to us for prenatal consultation during next pregnancy. We performed prenatal genetic diagnosis for the fetus. The result of Sanger sequencing for c.7235delinsGT (p.Thr2412fs) in SRCAP gene showed that the fetus did not carry the variant, so the fetus has been born successfully. The newborn does not show any similar symptom to the proband till one month. CONCLUSION:This case confirms that the c.7235delinsGT (p.Thr2412fs) variant in the SRCAP gene is associated with FHS and expands the spectrum of SRCAP variants.

Most patients with ovarian cancer experience disease recurrence or progression, and ultimately progress to platinum resistance. Standard treatments for platinum-resistant ovarian cancer (PROC) include non-platinum chemotherapy, targeted agents, and immunotherapy. Despite recent advances in individualized management of PROC, median progression-free survival remains limited. Effective treatments are still lacking for PROC treatment. Given the current landscape of immunotherapy in ovarian cancer, research is ongoing to investigate immune modulators to counteract immune escape and enhance the efficacy of immune checkpoint inhibitors. Here, we reported a successful administration of a triple regimen comprising pembrolizumab, lenvatinib and metronomic cyclophosphamide, as the third-line treatment in a patient with PROC. This combination resulted in a durable response, with a PFS of 52 months as of the last follow up. This is the first report on this triple regimen in PROC and its promising outcome suggested that this regimen deserves further investigation as a potential therapeutic option for PROC.

Hepatoid adenocarcinoma of the ovary represents a rare and malignant extrahepatic tumor that shares morphological and immunophenotypic similarities with hepatocellular carcinoma. Due to the ambiguous histomorphology and aggressive behavior, the diagnosis and management of hepatoid adenocarcinoma of the ovary present unique challenges. Here, we present a 67-year-old woman with massive ascites and disseminated peritoneal implants at initial diagnosis. She was treated with six cycles of neoadjuvant therapy (albumin-bound paclitaxel + nedaplatin + bevacizumab) and a debulking surgery, followed by eight cycles of postoperative adjuvant therapy (albumin-bound paclitaxel + carboplatin + bevacizumab). Elaborate pathology workup found significant involvement of angiogenesis in the tumor and confirmed the diagnosis via immunohistochemistry. Further molecular characterization of the tumor by whole-exome sequencing (WES) revealed a novel heterozygous germline mutation (NM_000057.2, c.1290_1291delinsATCAGGCCTCCATAG, p.Y430fs1) in gene BLM, likely pathogenic, suggesting a potential candidate for Poly (ADP-ribose) polymerase (PARP) inhibitors. For the maintenance therapy, she received a combination of the PARP inhibitor niraparib and the antiangiogenic anlotinib. As of now, the patient has achieved a partial response, with no apparent evidence of disease progression observed nearly 30 months. Our study sheds light on the WES-based profiling in rare cancers to screen for any treatable targets with otherwise no standard therapeutic options. The promising results with the niraparib-anlotinib combination suggest its potential as a maintenance therapy option for hepatoid adenocarcinoma of the ovary, which warrants validation in future larger cohort.

Endometriosis is a common gynecological disease caused by the implantation of active endometrial cells outside the uterine cavity. In most cases, endometriosis occurs in the pelvic area, such as the ovary, Douglas' pouch, or uterine sacral ligament. Some rare cases of extrapelvic endometriosis can also occur in the perineum, urinary system, gastrointestinal tract, nervous system, chest, subcutaneous tissue, and skin. Endometriosis of the perineum is usually secondary to obstetric trauma, such as perineal laceration or episiotomy. To date, few cases of spontaneous perineal endometriosis have been reported. Herein, we report a rare case of spontaneous deep perineal endometriosis. Notably, the patient had typical symptoms of regular pain during menstruation with no history of delivery or perineal trauma. The patient recovered well after postoperative gonadotropin releasing hormone agonist injection.

BackgroundUrachal carcinoma (UrC) is a rare malignancy with no known specific early symptoms. It is often diagnosed at advanced stages and is associated with poor prognosis.Case presentationThis study presents a rare case of urachal adenocarcinoma (UrAC) invading the bladder and vagina in a female patient. Initially, the patient was misdiagnosed as having a primary cervical adenocarcinoma 2.5 years prior. Subsequently, anterior pelvic exenteration and bilateral ureterocutaneostomies were performed. Twenty months after the first surgery, the patient was diagnosed with rectal metastasis and received gemcitabine chemotherapy. After achieving a stable disease state, the patient underwent laparoscopic ultralow rectal anterior resection, ultralow anastomosis of the sigmoid colon and rectum, prophylactic transverse colostomy, and right common iliac and external iliac lymph node dissection. The patient then received a cycle of postoperative chemotherapy with oxaliplatin and capecitabine; however, treatment was stopped due to adverse reactions. The patient continues to receive regular follow-ups, and her general condition is good.ConclusionsUrC is rare, and preoperative differential diagnosis is difficult. This is the first report of UrC being misdiagnosed as cervical cancer. The presented case highlights the importance of accurate histopathological examination and comprehensive analysis. Anterior pelvic exenteration was also identified as a potentially effective treatment strategy for patients with local pelvic recurrence of UrC, although further investigation is required.

Despite the improvements in clinical outcomes for patients with Diffuse Large B-Cell Lymphoma (DLBCL), a significant proportion of those patients still face challenges with refractory/relapsed (R/R) disease after receiving first-line R-CHOP treatment. Characterizing the heterogeneity of the tumor microenvironment (TME) in diffuse large B cell lymphoma (DLBCL) is crucial for understanding relapsed/refractory disease. However, the complex and diverse nature of the TME has impeded progress. Here, using single-cell RNA sequencing(scRNA-seq), we explored the DLBCL landscape at single-cell resolution, profiling 77,344 cells from both primary and relapsed DLBCL patients. We further investigated the shared and distinct molecular and cellular features of tumor microenvironment in both primary and relapsed DLBCL tumors by integrating next-generation DNA sequencing data and multiple scRNA-seq datasets from total 72,351 cells. Our results demonstrated that there was a significant decrease of CD4+CXCR5+PD-1- Tfh cells, along with excessive activation of the TNF-NFκB signaling pathways in malignant B cells in R/R disease. Furthermore, by using multiplex IHC, we confirmed that CD4+CXCR5+PD-1- Tfh cells are prognostic and predictive biomarkers for response to R-CHOP treatment. As a proof of concept, we successfully generated mutilplexed images of CD4+CXCR5+PD-1- Tfh cells from a single DAPI staining in human DLBCL tissues through using generative artificial intelligence. Our study offers critical insights into the heterogeneity and molecular features of DLBCL, shedding light on the crucial role of CD4+CXCR5+PD-1- Tfh cells in the recurrent process. ### Competing Interest Statement The authors H.J., P.W., S.Y. H.K. and X. Z are co-inventors on patents for the methods described herein filed by Force Biotech Ltd. H.J. is a co-founder of Force Biotech Ltd.

OBJECTIVE:To investigate the prognostic significance of molecular classification on treatment outcomes of fertility-sparing treatment (FST) in early-stage endometrial cancer (EC), and its potential in optimizing fertility-sparing management. METHODS:Patients with early-stage EC who received FST with ProMisE classification were investigated. Oncological and reproductive outcomes were compared across four molecular subtypes. Factors influencing complete response (CR) were analyzed. RESULTS:Among 116 molecularly classified patients, 80 were evaluated for therapeutic effects, including 64 (80.0 %) p53wt, 7 (8.7 %) MMR-D, 5 (6.3 %) POLE EDM, and 4 (5.0 %) p53abn. Overall CR rates were comparable across four molecular subtypes, with 92.2 % of p53wt, 71.4 % of MMR-D, 100.0 % of POLE EDM, and 75.0 % of p53abn (P = 0.145). MMR-D patients needed the longest median treatment time to achieve CR (7.9 months, range 3.5-15.9), while POLE EDM required the shortest (3.0 months, range 2.8-6.4), followed by p53abn (3.5 months, range 3.0-3.7) and p53wt (3.7 months, range 2.2-22.8) (P = 0.049). Among 14 p53wt patients with superficial myometrial invasion (MI) or G2 histology, 13 (92.9 %) achieved CR, and of 8 who attempted to conceive,4 delivered. Multivariable analysis identified MMR-D, superficial MI and insulin resistance negatively predicted CR, while POLE EDM was a positive factor. CONCLUSIONS:Molecular classification of EC may serve as a tool for predicting response to FST and assist in identifying candidates for FST. POLE EDM patients tended to obtain promising outcomes. MMR-D cases should be cautiously administrated for FST with close surveillance. Patients with p53wt demonstrated favorable outcomes, including those with superficial MI or G2 EC. Patients with endometrium-confined p53abn tumors may benefit from FST. However, given the small sample sizes of certain subtypes, further investigation is necessary to validate these findings.

Pancreatic ductal adenocarcinoma (PDAC) is a highly fibrotic and stiff tumor, and tumor-associated macrophages (TAMs) are pivotal in driving ECM remodeling, PDAC progression and immune evasion. The contribution of mechanical cues to monocyte differentiation into TAMs remains largely unexplored. Here we show that mechanical force is required for monocyte-to-macrophage differentiation. PYK2, as an innovative immunomechanical checkpoint, de facto governs this differentiation process. We demonstrated that PYK2 responds to mechanical signals within the tumor microenvironment (TME) via Piezo1 and integrins, leading to its activation and subsequent F-actin polymerization. Activated PYK2 then translocates to the nucleus, where it engages with promoters of genes governing mechanotransduction and differentiation, including ACTR3 and RELA. Targeted deletion of PYK2 impairs the differentiation and polarization of monocyte-derived macrophages, reshapes the PDAC microenvironment, and enhances the efficacy of anti-PD-1 immunotherapy. These findings underscore the critical role of mechanical cues in monocyte differentiation and suggest that targeting PYK2 is a promising strategy to modulate TAM function and improve immunotherapy outcomes in patients with PDAC. ### Competing Interest Statement The authors H.J., P.W., W.Y.X. and X.Y. are co-inventors on patents for the methods described herein filed by Force Biotech Ltd.. H.J. and Q.W. are co-founders of Force Biotech Ltd..

BACKGROUND:Several risk factors have been identified that compromise the treatment outcome in patients with early-to-mid-stage cervical cancer (CC) who are primarily treated with radical surgery. However, there is no report on the impact of intraoperative frozen pathology examination of vaginal margins on the prognosis of patients with CC. This study aimed to conduct a randomized controlled trial (RCT) to determine whether selective vaginal resection can reduce the incidence of operative complications and the risk of postoperative radiotherapy. The impact of the length of the vagina removed in radical hysterectomy (RH) on prognosis and quality of life (QoL) for IB2-IIA2 CC patients will be investigated. METHODS:A multicenter, non-inferiority, RCT at 7 institutions in China is designed to investigate the effect of intraoperative frozen pathology exam of vaginal margin in RH on the survival outcomes for patients with IB2-IIA2 CC. Eligible patients aged 18-70 years will be randomly assigned online by one-to-one random allocation to receive intraoperative frozen pathology exam of vaginal margin or not. If frozen pathology indicates positive margin, continue resection of 1 centimeter of vaginal tissue until negative margin is achieved. The primary end point is 2-year disease-free survival (DFS). Adverse events (AEs) caused by further vagina resection, 5-year DFS, 2-year overall survival (OS), 5-year OS and AEs caused by radiotherapy and QoL are secondary end points. A total of 310 patients will be enrolled from 7 tertiary hospitals in China within 3-year period and followed up for 5 years. TRIAL REGISTRATION:Chinese Clinical Trial Registry Identifier: ChiCTR2000035668.

Dysregulated proteome is an essential contributor in carcinogenesis. Protein fluctuations fuel the progression of malignant transformation, such as uncontrolled proliferation, metastasis, and chemo/radiotherapy resistance, which severely impair therapeutic effectiveness and cause disease recurrence and eventually mortality among cancer patients. Cellular heterogeneity is widely observed in cancer and numerous cell subtypes have been characterized that greatly influence cancer progression. Population-averaged research may not fully reveal the heterogeneity, leading to inaccurate conclusions. Thus, deep mining of the multiplex proteome at the single-cell resolution will provide new insights into cancer biology, to develop prognostic biomarkers and treatments. Considering the recent advances in single-cell proteomics, herein we review several novel technologies with particular focus on single-cell mass spectrometry analysis, and summarize their advantages and practical applications in the diagnosis and treatment for cancer. Technological development in single-cell proteomics will bring a paradigm shift in cancer detection, intervention, and therapy.

Objective: To investigate the role of the dedicator of cytokinesis 6 gene (DOCK6) in epithelial ovarian cancer (EOC). Methods: The expression of DOCK6 was measured through immunohistochemistry in samples from sixty-five EOC patients. The correlations between DOCK6 immunoreactivity and different clinicopathological characteristics were determined by Pearson's chi 2 test or Fisher's exact test. Different clinicopathological characteristics in relation to patient survival were evaluated by the Kaplan-Meier survival analysis and multivariate Cox regressions. Results: High DOCK6 expression in EOC tissues was positively associated with an advanced (III+IV) Federation International of Gynecology and Obstetrics (FIGO) stage (P=0.01) and high tumor grade (P=0.01). Using multivariate CI=1.39-106.28) and any residual tumor (P=0.02, HR=3.14, 95% CI=1.19-8.27) were shown to be independent prognostic factors. Conclusion: The overexpression of DOCK6 in EOC tissues was associated with advanced FIGO stage, suggesting that DOCK6 might be involved in the progression of EOC. More importantly, these data validate DOCK6 expression in addition to two pathological parameters (FIGO stage and residual tumor) as independent prognostic markers for EOC patients.

BACKGROUND:The EDGE SP1000 is a newly developed single-port (SP) robotic surgical system whose clinical evaluation in gynaecology has not yet been addressed.METHODS:This is a single-arm clinical trial evaluating the perioperative outcomes of patients receiving EDGE SP1000 assisted surgeries. Patients with either benign or malignant gynaecological diseases suitable for robotic surgery were included, and their data were prospectively collected.RESULTS:Eighteen patients were included and 8 of them had malignant conditions. The total operative time was 190.1 ± 83.3 min for benign diseases and 254.4 ± 59.4 min for malignant diseases. The mean estimated blood loss was 25 mL (range, 5-100). No assistant ports or conversions were required. No perioperative complications occurred. Overall satisfaction with the umbilical wounds was expressed at the 1-month follow-up.CONCLUSION:EDGE SP1000 SP robotic surgical system is technically feasible and safe in various gynaecological surgeries with good cosmetic effects.

Background:Radical hysterectomy (RH) is considered a cornerstone in the treatment of early-stage cervical cancer. However, the debate surrounding the optimal surgical approach, whether minimally invasive or open surgery, remains controversial. The objective of this trial is to evaluate the survival outcomes of cervical cancer patients who undergo different surgical approaches.Methods:This study is designed as a prospective, multicenter, open, parallel, and randomized controlled trial. A total of 500 patients diagnosed with stage IA1 with LVSI, IA2, IB1, or IB2 (2018 FIGO) will be recruited. Recruitment of participants started in November 2020. The participants will be randomly assigned to one of three groups: conventional laparoscopic RH, gasless laparoscopic RH, or abdominal RH. The primary endpoint of this trial is the 2-year disease-free survival (DFS) rate. The secondary endpoints will include the 2-year overall survival (OS) rate, 5-year DFS/OS, recurrence rates, operation time, intraoperative blood loss, surgery-related complications, and impact on quality of life (QoL).Discussion:We expect this trial to provide compelling and high-quality evidence to guide the selection of the most appropriate surgical approach for early-stage cervical cancer.Clinical trial registration:Chinese Clinical Trial Register, identifier ChiCTR2000035515.

This is an annual report issued by the Department of Gynecology of West China Second University Hospital of Sichuan University (WCSUH-SCU) to document the achievements of the gynecologic surgery teams at WCSUH-SCU in 2020. Patients who received gynecologic surgeries between January 1, 2017 and December 31, 2020 in the Department of Gynecology were retrospectively collected. Detailed data on surgical volume and procedures for different gynecologic diseases (cervical cancer, endometrial cancer, ovarian cancer, endometriosis, pelvic dysfunction and genital tract malformation) were analyzed separately. In the year 2020, 71 doctors (19 senior doctors, 17 associate senior doctors, 28 attending doctors, and 7 residents) performed 12,990 surgical procedures for 1,036 cervical cancer patients, 547 endometrial cancer patients, 544 ovarian cancer patients, 3,337 endometriosis patients, pelvic dysfunction patients 231 and genital malformation patients 42. The total surgical volume decreased by 944 (7.51%) over 2019. Accomplishments of research and education of the department’s surgical teams were also declared. The department also made significant progress in scientific research, education, and other areas in 2020. All staff in the department will continue to deliver quality health care, achieve innovative research and education, and improve the department’s academic impact.

Background: The McCune -Albright syndrome (MAS) (OMIM#174800) is a rare congenital disease, involving a triad of fibrous dysplasia (FD), caf & eacute; au lait skin spots, and peripheral precocious puberty; however, other endocrinological problems are also noted. The rarity of this disease and its variable clinical manifestations have led to delayed diagnoses and misdiagnoses. We report a case that was diagnosed by laparoscopy for early intervention to decrease skeletal lesions. Case Description: We reported the case of a 5 -year -old East Asian Chinese girl with breast enlargement, vaginal bleeding, and an ovarian cyst. Examination revealed normal anthropometric parameters. Pelvic ultrasound identified right ovarian cyst and multiple follicles. Biochemical investigations before and after cystectomy revealed no changes in the follicle -stimulating hormone and luteinizing hormone levels. We performed a cystectomy and collected a small tissue sample from the right ovary for genetic sequencing. She was diagnosed with MAS based on a genetic analysis of the ovarian tissue after laparoscopic cystectomy. Genetic testing of the right ovarian tissue revealed a mutation in guanine nucleotide -binding protein of the alpha -stimulating activity polypeptide (GNAS) (p.Arg201 + p.Gln227), and cyst was pathologically diagnosed as a follicular cyst. The patient recovered immediately after the surgery. She was treated with oral vitamin D subsequently and both of her breasts decreased in size and no vaginal bleeding occurred until the last follow-up. The patient had no caf & eacute; au lait skin spots or FD during follow-up. Conclusions: Our observations indicate that early diagnosis and intervention are crucial for improving the prognosis of patients with MAS. Ovarian cystectomy, when indicated, should be considered for establishing the diagnosis of MAS on a histological and genetic basis.