The impact of Paclitaxel-based hyperthermic intraperitoneal chemotherapy in advanced high-grade serous ovarian cancer patients - interim analysis of safety and immediate efficacy of a randomized control trial (C-HOC trial).

OBJECTIVE: This study evaluates the potential superiority of combining paclitaxel-based hyperthermic intraperitoneal chemotherapy (HIPEC) with sequential intravenous neoadjuvant chemotherapy over intravenous neoadjuvant chemotherapy alone in Chinese patients with Federation of Gynecology and Obstetrics (FIGO) stage IIIC, IVA and IVB high-grade serous ovarian/fallopian tube carcinoma (HGSOC). This interim analysis focuses on the safety and immediate efficacy of both regimens to determine the feasibility of the planned trial (C-HOC Trial). METHODS: In a single-center, open-label, randomized control trial, FIGO stage IIIC, IVA, and IVB HGSOC patients (FAGOTTI score ≥ 8 during laparoscopic exploration) unsuitable for optimal cytoreduction in primary debulking surgery (PDS) were randomized 2:1 during laparoscopic exploration. The Experiment Group (HIPEC Group) received one cycle of intraperitoneal neoadjuvant laparoscopic hyperthermic intraperitoneal chemotherapy (paclitaxel) followed by three cycles of intravenous chemotherapy (paclitaxel plus carboplatin), while the Control Group received only three cycles of intravenous chemotherapy. Both groups subsequently underwent interval debulking surgery (IDS). The adverse effects of chemotherapy, postoperative complications, and pathological chemotherapy response scores (CRS) after IDS were compared. RESULTS: Among 65 enrolled patients, 39 HIPEC Group and 21 Control Group patients underwent IDS. Grade 3-4 chemotherapy-related adverse effects were primarily hematological with no significant differences between the two groups. The HIPEC Group exhibited a higher proportion of CRS 3 (20.5% vs. 4.8%; P = 0.000). R0 resection rates in IDS were 69.2% (HIPEC Group) and 66.7% (Control Group). R2 resection occurred in 2.6% (HIPEC Group) and 14.3% (Control Group) cases. No reoperations or postoperative deaths were reported, and complications were managed conservatively. CONCLUSIONS: Combining HIPEC with IV NACT in treating ovarian cancer demonstrated safety and feasibility, with no increased chemotherapy-related adverse effects or postoperative complications. HIPEC improved tumor response to neoadjuvant chemotherapy, potentially enhancing progression-free survival (PFS). However, the final overall survival results are pending, determining if HIPEC combined with IV NACT is superior to IV NACT alone.

Gastrointestinal Stromal Tumors (GISTs) Mimicking Primary Ovarian Tumors or Metastasizing to the Ovaries: A Systematic Literature Review.

Background: Gastrointestinal stromal tumors (GISTs) are a rare neoplasm, sometimes mimicking primary ovarian tumors (OTs) and/or metastasizing to the ovaries (M-OT). We performed a systematic literature review (SLR) of OTs and M-OTs, investigating differences in recurrence-free and overall survival. Methods: Our SLR was performed according to PRISMA guidelines, searching in Pubmed, Scopus, and Web of Science databases from inception until 21 April 2024. Results: Overall, 59 OTs (Group 1) and 21 M-OTs (Group 2) were retrieved. The absence of residual disease after surgery was achieved significantly in a higher percentage of patients with Group 1 GISTs (91.5%) compared with Group 2 GISTs (57.1%). Chemotherapy was more frequently administered to Group 2 patients (33% vs. 0%). Recurrence and deaths for disease were significantly more frequent in Group 2 than Group 1 cases (54.5% vs. 6.8%, and 37.5% vs. 9.8%, respectively). Conclusions: GISTs can rarely mimic primary ovarian cancers or even more rarely metastasize to the ovaries. Group 1 GISTs occurred in younger women, were not associated with elevated tumor markers, and had a better prognosis. In contrast, Group 2 GISTs occurred in older women, may exhibit elevated tumor markers, and presented a worse prognosis. However, no significant statistical difference for survival between the two studied groups was detected. Computed tomography scans can define the size of GISTs, which correlate to stage and prognostic risk classes. The gold standard treatment is complete surgical resection, which was achieved in almost all cases of Group 1 GISTs and in half of Group 2. Histopathology and immunohistochemistry are essential for the final diagnosis and guide chemotherapy treatment.

High-grade serous carcinoma of the fallopian tube in a young woman with chromosomal 4q abnormality: A case report.

BACKGROUND: Few studies have reported an association between an increased risk of acquiring cancers and survival in patients with 4q deletion syndrome. This study presents a rare association between chromosome 4q abnormalities and fallopian tube high-grade serous carcinoma (HGSC) in a young woman. CASE SUMMARY: A 35-year-old woman presented with acute dull abdominal pain and a known chromosomal abnormality involving 4q13.3 duplication and 4q23q24 deletion. Upon arrival at the emergency room, her abdomen appeared ovoid and distended with palpable shifting dullness. Ascites were identified through abdominal ultrasound, and computed tomography revealed an omentum cake and an enlarged bilateral adnexa. Blood tests showed elevated CA-125 levels. Paracentesis was conducted, and immunohistochemistry indicated that the cancer cells favored an ovarian origin, making us suspect ovarian cancer. The patient underwent debulking surgery, which led to a diagnosis of stage IIIC HGSC of the fallopian tube. Subsequently, the patient received adjuvant chemotherapy with carboplatin and paclitaxel, resulting in stable current condition. CONCLUSION: This study demonstrates a rare correlation between a chromosome 4q abnormality and HGSC. UBE2D3 may affect crucial cancer-related pathways, including P53, BRCA, cyclin D, and tyrosine kinase receptors, thereby possibly contributing to cancer development. In addition, ADH1 and DDIT4 may be potential influencers of both carcinogenic and therapeutic responses.

Incidence and Causes of Tubal Occlusion in Infertility: A Retrospective Cohort Study.

Background and Objectives: Fallopian tubal pathology is a primary risk factor for female infertility, with simple proximal disease and proximal disease extending more distally being more common than pure distal occlusion. Proximal tubal occlusion is often attributed to ascending events, such as pelvic inflammatory disease. Conversely, while distal occlusion can also be attributable to ascending pelvic inflammatory disease, it can also have a pelvic origin, such as through endometriosis and ruptured appendicitis. The aim of this study was to identify certain causes of infertility and their association with tubal occlusion. The focus was on the location of tubal occlusion, uni- versus bilateral occlusion, and other causes of infertility, including male factors. Methods: In a retrospective study cohort study, 373 women aged between 18 and 40 years, treated from 1 January 2017 to 31 December 2022, were included. Fallopian tube patency was tested using either hysterosalpingography, hysterosalpingo-contrast sonography, or laparoscopic chromopertubation. Results: In total, 95 of 373 women (25.5%) revealed at least one occluded tube, with unilateral occlusion being more common than bilateral occlusion (60/95, 63.2% vs. 35/95, 36.8%). The majority of tubal occlusions occurred proximally (86.2%). According to the adjusted multivariate regression models, the presence of hydrosalpinx (odds ratio, OR, 13.323, 95% confidence interval, CI: 2.679-66.253, p = 0.002), myomas (OR 2.108, 95%CI: 1.008-4.409; p = 0.048), and an abnormal sperm test result of the male partner (OR 2.105, 95%CI: 1.156-3.833; p = 0.015) were statistically significant associated factors for tubal occlusion. Conclusions: Fallopian tube patency testing is still of major relevance in fertility evaluation. The presence of uterine myomas, hydrosalpinges, and a male factor significantly increase the risk.

Human peritoneal fluid exerts ovulation- and nonovulation-sourced oncogenic activities on transforming fallopian tube epithelial cells.

Secretory cells in the fallopian tube fimbria epithelium (FTE) are regarded as the main cells of origin of ovarian high-grade serous carcinoma (HGSC). Ovulation is the main cause of FTE oncogenesis, which proceeds through a sequence of TP53 mutations, chromosomal instability due to Rb/cyclin E aberration, in situ carcinoma (STIC), and metastasis to the ovary and peritoneum (metastatic HGSC). Previously, we have identified multiple oncogenic activities of the ovulatory follicular fluid (FF), which exerts the full spectrum of transforming activity on FTE cells at different stages of transformation. After ovulation, the FF is transfused into the peritoneal fluid (PF), in which the FTE constantly bathes. We wondered whether PF exerts the same spectrum of oncogenic activities as done by FF and whether these activities are derived from FF. By using a panel of FTE cell lines with p53 mutation (FT282-V), p53/CCNE1 aberrations (FT282-CCNE1), and p53/Rb aberrations plus spontaneous transformation, and peritoneal metastasis (FEXT2), we analyzed the changes of different transformation phenotypes after treating with FF and PF collected before or after ovulation. Similar to effects exhibited by FF, we found that, to a lesser extent, PF promoted anchorage-independent growth (AIG), migration, anoikis resistance, and peritoneal attachment in transforming FTE cells. The more transformed cells were typically more affected. Among the transforming activities exhibited by PF treatment, AIG, Matrigel invasion, and peritoneal attachment growth were higher with luteal-phase PF treatment than with the proliferative-phase PF treatment, suggesting an ovulation source. In contrast, changes in anoikis resistance and migration activities were similar in response to treatment with PF collected before and after ovulation, suggesting an ovulation-independent source. The overall transforming activity of luteal-phase PF was verified in an i.p. co-injection xenograft mouse model. Co-injection of Luc-FEXT2 cells with either FF or luteal-phase PF supported early peritoneal implantation, whereas co-injection with follicular-phase PF did not. This study, for the first time, demonstrates that PF from ovulating women can promote different oncogenic phenotypes in FTE cells at different stages of malignant transformation. Most of these activities, other than anoikis resistance and cell migration, are sourced from ovulation.

Misdiagnosis of a Drain-site Hernia Containing Fallopian Tube Fimbria on 18F-FDG PET/CT.

In a 55-year-old woman with sigmoid colon cancer, a subcutaneous mass in the left lower abdomen was incidentally found and gradually enlarged. For further diagnosis and staging, an 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography scan was performed, which revealed a subcutaneous mass in the left lower abdomen with mild uptake of 18F-FDG, suggesting the possibility of metastasis. However, post-surgery and pathological confirmation, this mass was diagnosed as a drain-site hernia containing fallopian tube fimbria, which is extremely rare but should be considered in the differential diagnosis of subcutaneous mass in the lower abdomen.

Metastasis of colorectal cancer to the uterine body and fallopian tube: case report and literature review.

Colorectal cancer typically metastasizes to the peritoneum, liver, and lungs. However, metastases to the fallopian tube and uterus are uncommon. This case report delves into this rare occurrence of metastasis and discusses its characteristics, diagnostic methods, and treatments based on an extensive literature review. We present the case of a 61-year-old female patient who underwent her initial hospitalization for da Vinci robotic surgery to address colorectal cancer, stage pT3N0M0. However, during routine postoperative follow-up 6 months later, a localized rectal recurrence was detected. The patient commenced chemoradiotherapy with full response. Subsequently, the patient was readmitted due to pelvic pain again, and a magnetic resonance imaging scan revealed an abnormal mass in the patient's left fallopian tube and uterine corpus, infiltrating the myometrium. Consequently, total hysterectomy with bilateral adnexectomy was performed, along with omentectomy, which confirmed metastatic involvement from rectal cancer upon postoperative pathological examination. This case may inform further diagnosis and treatment of colorectal cancer metastasis to the fallopian tube.

An Incidental Fallopian Tube Focal Serous Tubal Intraepithelial Lesion (STIL) Discovered on a Postoperative Pathology Report Following Hysterectomy and Salpingectomy: A Case Report.

A focal serous tubal intraepithelial lesion (STIL) is a rare lesion found on fallopian tubes that are characterized by atypical epithelial cells exhibiting morphological abnormalities with the accumulation of mutant p53 proteins. The p53 gene is a tumor suppressor gene, and when mutated gives rise to mutant p53 proteins that promote cancer cell growth and survival. We present a case of a 47-year-old gravida 2, para 2002 (G2P2) female who presented to the outpatient clinic with bilateral lower quadrant abdominal pain and back pain of four years' duration. The patient's history included endometriosis with lysis of adhesions and gynecological laparoscopy, leiomyomata, infertility, ovarian cyst, dysmenorrhea, two full term births, and Essure implants used for contraception; her family history included maternal grandfather with breast cancer. Multiple fibroids and endometriosis were confirmed on pelvic ultrasound (US) and magnetic resonance imaging (MRI). Due to worsening pain, the patient chose to have an elective hysterectomy and Essure implant removal with bilateral salpingectomy. The postoperative pathology report revealed a right fallopian tube with a STIL. Multiple genetic mutations are known to contribute to the development of STILs including p53 and the breast cancer gene (BRCA). There are two BRCA genes, BRCA1 and BRCA2, that have many functions including producing proteins that repair damaged DNA. When mutated, this allows cells to divide and change rapidly, leading to certain types of cancer. Given the patient's family history of breast cancer, the patient was tested for BRCA1 and BRCA2 for which the results were negative. However, even without having a BRCA mutation that is known to increase the risk of ovarian, fallopian tube, and peritoneal cancers, STILs continue to pose an increased risk of high-grade serous ovarian carcinoma (HGSOC). This case demonstrates the reasoning behind prophylactic salpingectomies alongside hysterectomies and the significance of the postoperative pathology report from gynecological procedures.

Four cases of isolated fallopian tube torsion successfully treated with laparoscopic surgery:A case series.

We report four cases of isolated fallopian tube torsion (IFTT) successfully treated with laparoscopic surgery over the past 10 years. Two young women (each 19 years old) were IFTT with paraovarian cyst (POC) and tubal preservation was possible with detorsion and cystectomy. The other two patients (a 41-year-old woman with hydrosalpinx and a 50-year-old woman with hematosalpinx) underwent salpingectomy and adnexectomy, respectively, because there was no desire for tubal preservation. One patient had emergency surgery due to severe abdominal pain, one had semi-emergency surgery due to mild abdominal pain, and the other two were diagnosed during scheduled surgery without symptoms.Although IFTT was considered a very rare disease, our case series and recent reports suggest that it may have been underestimated, as it accounts for approximately 10% of adnexal torsion cases. Preoperative diagnosis of IFTT may be more difficult than for adnexal torsion because of its infrequency and nonspecific, vague clinical symptoms.　Since the prevalent age for this disease is young, as in our first 2 patients, early surgical intervention to preserve the fallopian tubes should be chosen when necessary, and it seems to be important for gynecologists to be aware of this disease for earlier diagnosis and appropriate surgical intervention.

Endometrioid carcinoma of the fallopian tube misdiagnosed as an infected endometrioma: A case report.

INTRODUCTION: Fallopian tube cancer is a rare tumor, representing between 0.3 and 1.8 % of all malignant tumors in the gynecological sphere. Due to the proximity of the uterus and ovary, the diagnosis of primary fallopian tube cancer is very difficult to establish and relies on very strict criteria. The endometrioid form is exceptional and of controversial etiopathogenesis. Only a few cases have been previously reported. Diagnosis most often occurs incidentally during histological examination. This case presents a distinctive aspect with the rare occurrence of endometrioid-type fallopian tube cancer, notably associated with endometriosis, and initially misdiagnosed as an infected endometrioma. It underscores the diagnostic complexities encountered in identifying primary fallopian tube cancer. CASE REPORT: We present the case of a 49-year-old patient, followed for chronic pelvic pain associated with menorrhagia. Imaging revealed a myomatous and adenomyotic uterus, a right ovarian endometrioma, and a left multicystic ovarian formation with thick walls, measuring 135 mm, requiring histological verification. She underwent an exploratory laparotomy. During the procedure, extensive retro- and supravaginal adhesive tissue involving the uterus, both adnexa, and the digestive tract was found. Careful adhesiolysis was performed. The left adnexa harbored a formation suggestive of an infected endometrioma. A total hysterectomy with bilateral adnexectomy and peritoneal washing was performed. The postoperative course was uneventful. Histopathological examination revealed an endometrioid carcinoma of the left fallopian tube, classified as pT1a according to FIGO guidelines. DISCUSSION: Tubal cancer is a rare cancer of unknown etiology, underestimated, and sometimes confused with ovarian pathology. Preoperative diagnosis is difficult because the clinical presentation is polymorphic and imaging is nonspecific. The endometrioid form is exceptional and of controversial etiopathogenesis. Treatment mirrors that of malignant epithelial ovarian tumors, with prognosis depending on FIGO stage and histological type. CONCLUSION: Due to its unpredictable nature, fallopian tube cancer should not be overlooked as a differential diagnosis for any adnexal mass.

Modeling of Intracellular Taurine Levels Associated with Ovarian Cancer Reveals Activation of p53, ERK, mTOR and DNA-Damage-Sensing-Dependent Cell Protection.

Taurine, a non-proteogenic amino acid and commonly used nutritional supplement, can protect various tissues from degeneration associated with the action of the DNA-damaging chemotherapeutic agent cisplatin. Whether and how taurine protects human ovarian cancer (OC) cells from DNA damage caused by cisplatin is not well understood. We found that OC ascites-derived cells contained significantly more intracellular taurine than cell culture-modeled OC. In culture, elevation of intracellular taurine concentration to OC ascites-cell-associated levels suppressed proliferation of various OC cell lines and patient-derived organoids, reduced glycolysis, and induced cell protection from cisplatin. Taurine cell protection was associated with decreased DNA damage in response to cisplatin. A combination of RNA sequencing, reverse-phase protein arrays, live-cell microscopy, flow cytometry, and biochemical validation experiments provided evidence for taurine-mediated induction of mutant or wild-type p53 binding to DNA, activation of p53 effectors involved in negative regulation of the cell cycle (p21), and glycolysis (TIGAR). Paradoxically, taurine's suppression of cell proliferation was associated with activation of pro-mitogenic signal transduction including ERK, mTOR, and increased mRNA expression of major DNA damage-sensing molecules such as DNAPK, ATM and ATR. While inhibition of ERK or p53 did not interfere with taurine's ability to protect cells from cisplatin, suppression of mTOR with Torin2, a clinically relevant inhibitor that also targets DNAPK and ATM/ATR, broke taurine's cell protection. Our studies implicate that elevation of intracellular taurine could suppress cell growth and metabolism, and activate cell protective mechanisms involving mTOR and DNA damage-sensing signal transducti.

Primary ovarian cancer combined with primary fallopian tube cancer: A case report.

BACKGROUND: Low grade serous carcinoma of the ovary (LGSOC) is a rare type of epithelial ovarian cancer with a low incidence rate. The origin of ovarian cancer has always been a hot topic in gynecological oncology research, and some scholars believe that the origin of ovarian malignant tumors is the fallopian tubes. Primary fallopian tube cancer is the lowest incidence of malignant tumors in the female reproductive system. There are only a few reports in the literature, but the mortality rate is very high. But in clinical practice, fallopian tube cancer is very common, but in most cases, it is classified as ovarian cancer. CASE SUMMARY: We report a 54 years old postmenopausal woman who was hospitalized with a lower abdominal mass and underwent surgical treatment. The final pathological confirmation was low-grade serous carcinoma of the right ovary and low-grade serous carcinoma of the left fallopian tube. No special treatment was performed after the surgery, and the patient was instructed to undergo regular follow-up without any signs of disease progression. CONCLUSION: The prognosis of LGSOC is relatively good, over 80% of patients still experience disease recurrence.

Comprehensive next-generation sequencing identifies novel putative pathogenic or likely pathogenic germline variants in patients with concurrent tubo-ovarian and endometrial serous and endometrioid carcinomas or precursors.

BACKGROUND: Endometrial serous carcinoma (ESC) and tubo-ovarian high-grade serous carcinoma (HGSC) are characterized by late-stage presentation and high mortality. Current guidelines for prevention recommend risk-reducing salpingo-oophorectomy (RRSO) in patients with hereditary mutations in cancer susceptibility genes. However, HGSC displays extensive genetic heterogeneity with alterations in 168 genes identified in TCGA study, but current germline testing panels are often limited to the handful of recurrently mutated genes, leaving families with rare hereditary gene mutations potentially at-risk. OBJECTIVE: To determine if there are rare germline mutations that may aid in early identification of more patients at-risk for ESC and/or HGSC by evaluating patients with concurrent ESC, HGSC or precursor lesions, and endometrial atypical hyperplasia (CAH) or low-grade endometrial endometrioid adenocarcinoma (LGEEA). METHODS: We performed targeted next-generation sequencing using TSO 500, a 523 gene panel, on formalin-fixed paraffin-embedded tumor and matched benign non-tumor tissue blocks from 5 patients with concurrent ESC, HGSC or precursor lesions, and CAH or LGEEA. RESULTS: We identified germline pathogenic, likely pathogenic or uncertain significance variants in cancer susceptibility genes in 4 of 5 patients - affected genes included GLI1, PIK3R1, FOXP1, FANCD2, INPP4B and H3F3C. Notably, none of these genes were included in the commercially available germline testing panels initially used to evaluate the patients at the time of their diagnoses. CONCLUSION: Comprehensive germline testing of patients with concurrent LGEEA or CAH and ESC, HGSC or precursor lesions may aid in early identification of relatives at-risk for cancer who may be candidates for RRSO with hysterectomy.

Robotic HIPEC with use of a vaginal GelPoint®.

Patients with advanced stage ovarian cancers commonly undergo hyperthermic intraperitoneal chemotherapy (HIPEC) following interval debulking via exploratory laparotomy. This video demonstrates the feasibility of HIPEC delivery via a minimally invasive approach with the use of a vaginal GelPoint® port. This video demonstrates a 56-year-old patient with Stage 3 bilateral fallopian tube cancer who underwent 3 cycles of neoadjuvant chemotherapy with cisplatin and paclitaxel. Prior to administration of HIPEC the patient underwent an uncomplicated robotic assisted radical hysterectomy, bilateral salpingo-oopherectomy and infracolic omentectomy. Additionally, the falciform ligament was transected. The vaginal cuff was then used for placement of the GelPoint® port. The inflow and outflow cannulas were placed at the level of the liver and pelvis robotically. To minimize risk of inadvertent spillage, robotic obturators were replaced. Prior to administration of HIPEC, 4 L of warm saline was administered. An additional safety check was performed with no areas of leak. Cisplatin was administered for 90 min followed by sodium thiosulfate and 3 L of normal saline. Confirmation of no residual fluid was noted laparoscopically. The patient was discharged 2 days postoperatively without postoperative complications. In this video we demonstrated the innovative technique of performing HIPEC via a minimally invasive approach, that typically requires an open procedure. With the use of a vaginal Gelpoint® we were able to safely administer intraperitoneal chemotherapy without risk to our patient. We were also able to minimize their length of hospital stay and expedite postoperative recovery. Further implementation of this technique may improve hospital resource allocation.

In vitro effect of hyoscine-N-butyl bromide and diclofenac sodium in human tuba uterina.

INTRODUCTION: To investigate the in vitro effect of diclofenac on tubal smooth muscle as an alternative to hyoscine-N-butyl bromide, which is used for premedication before hysterosalpingography (HSG). MATERIAL AND METHODS: Fallopian tubes were retrieved from seven healthy women after bilateral tubal ligation and in vitro contractility and histological studies were conducted using tissue bath and immunohistochemistry. RESULTS: Diclofenac sodium and hyoscine-N-butyl bromide did not significantly change the basal mean tension; however, they decreased the contractions induced by potassium chloride (KCl). The relaxant effect of diclofenac sodium and hyoscine-N-butyl bromide was not statistically significantly different. The presence of cyclooxygenase (COX)-2 enzyme in the fallopian tube was demonstrated by immunohistochemical studies. CONCLUSIONS: The in vitro relaxant effect of diclofenac sodium on the fallopian tube is similar to hyoscine-N-butyl bromide. Diclofenac may have the potential to be used as an alternative to hyoscine-N-butyl bromide in premedication in HSG.

Evaluation of tubal patency based on peak injection pressure in four-dimensional hysterosalpingo-contrast sonography among infertile females: a preliminary study.

Background: Although the application of four-dimensional hysterosalpingo-contrast sonography (4D-HyCoSy) has relatively good diagnostic accuracy for assessing the patency of the fallopian tubes, the evaluation process mainly relies on morphological findings of the fallopian tubes and pelvic cavity. The purpose of this study was to explore the relationship of peak injection pressure during 4D-HyCoSy and tubal patency to provide a quantitative indicator for the evaluation of fallopian tube patency. Methods: This study included infertile patients who underwent 4D-HyCoSy and laparoscopic chromopertubation (LC) between 2020 and 2022, with LC serving as the reference test for assessing tubal patency. For the HyCoSy procedure, the ultrasound contrast agent was injected automatically using a liquid injection machine, and real-time pressure values were recorded. Patients were classified based on tubal patency status in LC as bilaterally patent, unilaterally patent, or bilaterally nonpatent. The average peak injection pressure and contrast agent volume of different groups were compared. Receiver operating characteristic (ROC) curve analysis was employed to determine the cutoff value. Results: A total of 268 infertile patients were enrolled in the study. With LC as the standard examination, the sensitivity and specificity of 4D-HyCoSy in diagnosing nonpatent fallopian tubes were 91.1% and 95.1%, respectively. In general, peak injection pressure was observed to gradually increase as tubal patency decreased (P<0.001), with average peak injection pressures of 233.5±66.3, 338.8±99.8, and 469.6±63.1 mmHg in the bilaterally patent, unilaterally patent, and bilaterally nonpatent groups, respectively. The volume of contrast agent used in patients in the bilaterally nonpatent group was significantly lower than that in the other two groups (P<0.01), with average volumes of 22.7±6.3, 24.3±9.3, and 18.9±9.2 mL, respectively. When one fallopian tube was patent, the area under the curve (AUC) for distinguishing obstruction from patency of the other fallopian tube was 0.827, with a sensitivity of 79.8% and a specificity of 74.3% (cutoff value: 254.3 mmHg). Similarly, when one fallopian tube was nonpatent, the AUC was 0.866, with a sensitivity of 90.6% and a specificity of 78.3% (cutoff value: 401.3 mmHg). Conclusions: Peak injection pressure during 4D-HyCoSy demonstrates promising diagnostic performance in evaluating fallopian tube patency in infertile patients.

Systematic review and network meta-analysis of hydrosalpinx treatment before in vitro fertilization.

OBJECTIVES: To compare different methods to treat hydrosalpinx, based on both ablative and non-ablative approaches, in infertile patients before undergoing IVF-ET. METHODS: Systematic review and network meta-analysis (NMA) of comparisons between different treatments of hydrosalpinx in infertile patients undergoing IVF. DATA SOURCES: structured searches in common citation databases. Study inclusion criteria: peer-reviewed randomized trials (RCT) or cohort studies comparing effects of salpingectomy, laparoscopic proximal tubal occlusion (LTO), insertion of intratubal device (ITD), sclerotherapy, ultrasound-guided aspiration and no treatment, on live birth, ongoing pregnancy, clinical pregnancy as main outcomes, considering also miscarriage, ectopic pregnancy and complications as secondary outcomes. Principal NMA included RCT, and aggregated NMA of RCT and observational studies was carried out. Pooled effects have been estimated by Odds Ratio (OR) and its 95% confidence interval (CI) for direct and indirect-mixed comparisons, derived from random-effects models. Imprecision and heterogeneity of NMA estimations was assessed by comparison of its 95% CI with predefined intervals for clinically relevant size of effect (OR <0.9 or >1.1). Surface under the cumulative ranking curve (SUCRA) were used to predict treatment rankings for each outcome. RESULTS: Nine RCT were included in main analysis, plus 17 additional observational studies in additional analysis. NMA of RCT did not identify significant differences in the effect of compared treatments on live birth rate, and LTO was the option with the highest value of SUCRA (0.92, mean rank: 1.2). Salpingectomy and US-aspiration associated to a significant increase of ongoing pregnancy rate compared to no treatment, according to NMA results (NMA OR: 4.35; 95% CI: 1.7, 11.14 and 2.8; 95% CI: 1.03, 7.58 respectively). Salpingectomy had the highest SUCRA value (0.88, mean rank: 1.4). NMA estimated significant increase of clinical pregnancy rate for salpingectomy compared with no treatment (NMA OR: 2.24; 95% CI: 1.3, 3.86) as well as for LTO versus no treatment (NMA OR: 2.55; 95% CI: 1.2, 5.41). Both comparisons were affected by a high grade of heterogeneity. For clinical pregnancy, LTO was the intervention with highest SUCRA (0.85; mean rank: 1.6). Regarding secondary outcomes, feasible NMA estimates did not support significant differences between treatments effects. According to aggregated NMA including randomized and observational studies, sclerotherapy showed significant beneficial effects on live birth rate compared to no treatment (NMA (OR: 4.6; 95% CI: 1.21, 17.46). Compared with untreated patients, the aggregated NMA estimates a higher ongoing pregnancy rate in patients treated with salpingectomy (NMA OR: 3.35; 95% CI: 2.12, 5.12), US-aspiration (NMA OR: 2.16; 95% CI: 1.28, 3.65) and LTO (NMA OR: 2.46; 95% CI: 1.11, 5.43). Salpingectomy and LTO produced a higher beneficial effect compared to ITD, based on both direct and indirect comparisons. Salpingectomy obtained the highest SUCRA value in rank of effects on ongoing pregnancy (0.94; mean rank: 1.2). NMA found significant effects on clinical pregnancy for comparisons between the different active management procedures compared with no treatments, with the exception of ITD insertion. LTO had more increasing effect on clinical pregnancy rate compared with US-aspiration (NMA OR: 2.04; 95% CI: 1.05, 3.97), while for the rest of the comparisons between procedures no significant differences were identified. NMA ranked LTO as the treatment with a highest SUCRA value (0.91; mean rank: 1.5). NMA prediction models identified LTO as best intervention to reduce miscarriage (SUCRA value: 0.84; mean rank: 1.8), as sclerotherapy as safer option in terms of ovarian response to IVF stimulation. CONCLUSIONS: The present NMA fails to support the effectiveness of any option to treat hydrosalpinx before IVF in order to improve live birth rates, although the beneficial effect of salpingectomy and US aspirations on ongoing pregnancy rates and of both salpingectomy and LTO on clinical pregnancy rates emerges from our analysis, which reinforces current recommendations. Based on the aggregated analyses, sclerotherapy could be a promising alternative to conventional laparoscopic techniques, combined with a favorable safety profile. This article is protected by copyright. All rights reserved.

Evaluation of women's aging influence on sperm passage inside the fallopian tube using 3D dynamic mechanical modeling.

The fallopian tubes play an important role in human fertility by facilitating the spermatozoa passage to the oocyte as well as later actively facilitating the fertilized oocyte transportation to the uterus cavity. The fallopian tubes undergo changes involving biological, physical, and morphological processes due to women aging, which may impair fertility. Here, we have modelled fallopian tubes of women at different ages and evaluated the chances of normal and pathological sperm cells reaching the fertilization site, the ampulla. By utilizing a unique combination of simulative tools, we implemented dynamic three-dimensional (3D) detailed geometrical models of many normal and pathological sperm cells swimming together in 3D geometrical models of three fallopian tubes associated with different women's age groups. By tracking the sperm cell swim, we found that for all age groups, the number of normal sperm cells in the ampulla is the largest, compared with the pathological sperm cells. On the other hand, the number of normal sperm cells in the fertilization site decreases due to the morphological and mechanical changes that occur in the fallopian tube with age. Moreover, in older ages, the normal sperm cells swim with lower velocities and for shorter distances inside the ampulla toward the ovary. Thus, the changes that the human fallopian tube undergoes due to women's aging have a significant influence on the human sperm cell motility. Our model of sperm cell motility through the fallopian tube in relation to the woman's age morphological changes provides a new scope for the investigation and treatment of diseases and infertility cases associated with aging, as well as a potential personalized medicine tool for evaluating the chances of a natural fertilization per specific features of a man's sperm and a woman's reproductive system.

NB compounds are potent and efficacious FOXM1 inhibitors in high-grade serous ovarian cancer cells.

BACKGROUND: Genetic studies implicate the oncogenic transcription factor Forkhead Box M1 (FOXM1) as a potential therapeutic target in high-grade serous ovarian cancer (HGSOC). We evaluated the activity of different FOXM1 inhibitors in HGSOC cell models. RESULTS: We treated HGSOC and fallopian tube epithelial (FTE) cells with a panel of previously reported FOXM1 inhibitors. Based on drug potency, efficacy, and selectivity, determined through cell viability assays, we focused on two compounds, NB-73 and NB-115 (NB compounds), for further investigation. NB compounds potently and selectively inhibited FOXM1 with lesser effects on other FOX family members. NB compounds decreased FOXM1 expression via targeting the FOXM1 protein by promoting its proteasome-mediated degradation, and effectively suppressed FOXM1 gene targets at both the protein and mRNA level. At the cellular level, NB compounds promoted apoptotic cell death. Importantly, while inhibition of apoptosis using a pan-caspase inhibitor rescued HGSOC cells from NB compound-induced cell death, it did not rescue FOXM1 protein degradation, supporting that FOXM1 protein loss from NB compound treatment is specific and not a general consequence of cytotoxicity. Drug washout studies indicated that FOXM1 reduction was retained for at least 72 h post-treatment, suggesting that NB compounds exhibit long-lasting effects in HGSOC cells. NB compounds effectively suppressed both two-dimensional and three-dimensional HGSOC cell colony formation at sub-micromolar concentrations. Finally, NB compounds exhibited synergistic activity with carboplatin in HGSOC cells. CONCLUSIONS: NB compounds are potent, selective, and efficacious inhibitors of FOXM1 in HGSOC cells and are worthy of further investigation as HGSOC therapeutics.

Predictors of olaparib discontinuation owing to adverse drug events in patients with ovarian, peritoneal, or fallopian tube cancer: a retrospective observational study.

We investigated predictors of olaparib discontinuation owing to adverse effects. Patients with ovarian, peritoneal, or fallopian tube cancers treated with olaparib at Osaka Medical and Pharmaceutical University Hospital between April 2018 and September 2022 were included in this study. The exclusion criteria were as follows: discontinuation of treatment due to disease progression, use of anaemia medications, and use of cytochrome P450 (CYP3A4) inhibitors. The follow-up period was 90 d. Of the 46 eligible patients, 21 patients discontinued olaparib, including 15 patients with grade 3 or higher anaemia, eight patients with grade 3 or higher neutropenia, and four patients with non-haematological toxicity (including multiple onset). Multivariate logistic regression analysis showed that grade 4 neutropenia and anaemia progression to grades 2-3 due to chemotherapy administered before olaparib administration were predictors of olaparib discontinuation. The severity of neutropenia and anaemia due to chemotherapy before olaparib administration may be a potential marker for its discontinuation.