Multi-gene panel analysis in BRCA1/2-negative patients suspected of hereditary breast and ovarian cancer syndrome: Real-world data from a single institution.

AIM: Although BRCA1/2 is most frequently associated with hereditary breast and ovarian cancer (HBOC), many other related genes have been implicated. Therefore, we investigated the prevalence of non-BRCA1/2 genes associated with hereditary cancer predisposition in BRCA1/2-negative patients from the Department of Genetic Medicine and Services with breast and ovarian cancer using a multi-gene panel (MGP) analysis. METHODS: We conducted a retrospective MGP analysis (National Cancer Center Onco-Panel for Familial Cancer; NOP_FC) in BRCA1/2-negative patients with breast, ovarian, and overlapping breast/ovarian cancers who visited our genetic counseling between April 2004 and October 2022. RESULTS: NOP_FC was performed in 128 of the 390 BRCA test-negative cases (117 breast cancer, 9 ovarian cancer, and 2 overlapping breast/ovarian cancer cases). Among the BRCA1/2-negative patients, nine (7.7%) with breast cancer and one (11%) with ovarian cancer had pathogenic variants (PVs) in non-BRCA1/2 genes associated with breast and ovarian cancers, respectively. Five patients had PVs in RAD51D, two in PALB2, one in BARD1, one in ATM, and one in RAD51C. CONCLUSIONS: Additional MGP testing of germline genes associated with hereditary cancer predisposition syndrome in BRCA1/2-negative breast and ovarian cancer patients revealed PVs in non-BRCA1/2 breast cancer- and ovarian cancer-related genes in 7.7% of breast cancer and 11% of ovarian cancer. Therefore, additional testing may provide useful information for subsequent risk-reducing surgery and surveillance in BRCA1/2-negative patients.

Ovarian Mucinous Tumor Presenting Atypical Lobular Endocervical Glandular Hyperplasia-Like Appearance in a Patient With Germline STK11 p.F354L Variant: A Case Report.

Peutz-Jeghers syndrome (PJS) is associated with female genital lesions, such as cervical gastric-type adenocarcinoma and lobular endocervical glandular hyperplasia (LEGH). However, ovarian mucinous borderline tumors (OMBT) with atypical LEGH-like histology have not been described. The patient was a 60-year-old female with PJS clinically diagnosed at 23 years old with gastrointestinal polyposis. Abdominal distension was noted, and computed tomography scan revealed bilateral breast masses, multiple lung nodules, and a multicystic ovarian tumor. A needle biopsy revealed invasive ductal carcinoma of the breast. For the ovarian tumor, simple hysterectomy and bilateral salpingo-oophorectomy were performed. The left ovarian tumor was 25 × 20 × 12 cm in size and a multicystic tumor containing yellowish mucus without a solid part. Histologically, the cyst wall was covered with mucus cells with focal mild-to-moderate cellular atypia, forming LEGH-like architectures. The glandular cells were immunohistochemically positive for MUC5AC, MUC6 (focal), HIK1083 (focal), and HNF4α. Stromal invasion was not observed. Cervical lesions were not observed. The final pathological diagnosis was OMBT showing atypical LEGH morphology. Targeted sequencing of nontumor tissues revealed the germline STK11 p.F354L variant. Six months later, peritoneal dissemination of adenocarcinoma showing features similar to those of the ovarian tumor was observed, and the patient died of the disease. In summary, we report a case of OMBT with an atypical LEGH-like appearance in a patient with germline STK11 p.F354L variant. This case provides us with unresolved questions regarding the pathogenicity of this STK11 variant and the malignant potential of OMBT with this unusual morphology.

Characteristics and outcomes of neonates hospitalised with SARS-CoV-2 infection in the UK by variant: a prospective national cohort study.

OBJECTIVE: Neonatal infection with wildtype SARS-CoV-2 is rare and good outcomes predominate. We investigated neonatal outcomes using national population-level data to describe the impact of different SARS-CoV-2 variants. DESIGN: Prospective population-based cohort study. SETTING: Neonatal, paediatric and paediatric intensive care inpatient care settings in the UK. PATIENTS: Neonates (first 28 days after birth) with confirmed SARS-CoV-2 infection who received inpatient care, March 2020 to April 2022. Neonates were identified through active national surveillance with linkage to national SARS-CoV-2 testing data, routinely recorded neonatal data, paediatric intensive care data and obstetric and perinatal mortality surveillance data. OUTCOMES: Presenting signs, clinical course, severe disease requiring respiratory support are presented by the dominant SARS-CoV-2 variant in circulation at the time. RESULTS: 344 neonates with SARS-CoV-2 infection received inpatient care; breakdown by dominant variant: 146 wildtype, 123 alpha, 57 delta and 18 omicron. Overall, 44.7% (153/342) neonates required respiratory support; short-term outcomes were good with 93.6% (322/344) of neonates discharged home. Eleven neonates died: seven unrelated to SARS-CoV-2 infection, four were attributed to neonatal SARS-CoV-2 infection (case fatality 4/344, 1.2% 95% CI 0.3% to 3.0%) of which three were born preterm due to maternal COVID-19. More neonates were born very preterm (23/54) and required invasive ventilation (27/57) when delta variant was predominant, and all four SARS-CoV-2-related deaths occurred in this period. CONCLUSIONS: Inpatient care for neonates with SARS-CoV-2 was uncommon. Although rare, severe neonatal illness was more common during the delta variant period, potentially reflecting more severe maternal disease and associated preterm birth. TRIAL REGISTRATION NUMBER: ISRCTN60033461.

Gynecological technical notes for appropriate spacer injections.

BACKGROUND: Despite its efficacy, if adherence to dose constraints for surrounding normal tissues proves unattainable, the risk of late radiation-related adverse events after primary radiotherapy involving brachytherapy remains a noteworthy concern. Some studies suggest that similar to prostate radiotherapy, spacers may potentially reduce doses to surrounding healthy rectal or bladder tissues. However, guidance on spacer injections for gynecologic brachytherapy is scarce, and the optimal anatomical location for spacer placement remains undefined. We discuss maximizing the effects of spacers from an anatomical perspective. FINDINGS: As vesicovaginal and rectovaginal septa form part of the endopelvic fascia and are not uniform tissues, spacer injection resistance varies. In pelvic organ prolapse surgery, saline is injected into the anterior and posterior vaginal walls as a spacer, and the vagina, vesicovaginal septum, and bladder can be fluidly dissected. Relatively firm vesicovaginal septum tissue is used as a reconstructive organ, whereas rectovaginal septum tissue is less dense. Cervical cancer is invasive, involving surrounding fascia and ligaments. Ideally, the vesicovaginal and rectovaginal septa should be resected in radical hysterectomy. Here, spacer adaptation and the technical details of injection are described. When using ultrasound guidance for spacer injection, the target site should be adequately magnified, and the spacer ideally injected into the incision layer during radical hysterectomy. Finally, posthysterectomy, the intestinal tract may adhere to the vaginal cuffs. Therefore, artificial ascites may be useful; however, the spread depends on perioperative manipulation. CONCLUSIONS: Anatomical and surgical viewpoints are advantageous for safe, therapeutic, and replicable spacer injection administration.

Respiratory Distress Syndrome in Infants Delivered via Cesarean from Mothers with Preterm Premature Rupture of Membranes: A Propensity Score Analysis.

OBJECTIVE: This study aimed to clarify the effects of cesarean delivery on neonatal respiratory morbidity when women had preterm premature rupture of membranes. METHODS: This retrospective study included women with preterm premature rupture of membranes who delivered from 23 weeks to 33 weeks of gestation between January 2009 and December 2014. Neonatal outcomes were compared between infants delivered by cesarean section and those delivered vaginally. The primary outcome was respiratory distress syndrome (RDS). Neonatal intubation and mechanical ventilation periods were secondary outcomes. Propensity score matching was used to compare outcomes between cesarean and vaginal delivery cases. RESULTS: There were 101 cesarean deliveries and 89 vaginal deliveries. A comparison of the presence or absence of neonatal complications based on the delivery type indicated a higher occurrence of RDS with cesarean deliveries (P = 0.025). The intubation and mechanical ventilation periods were not significantly longer in neonates delivered via cesarean section. CONCLUSIONS: Cesarean delivery is a risk factor for neonatal RDS in women with preterm premature rupture of membranes. Trials identifying long-term neonatal prognoses are needed to further develop optimal management strategies in such cases.

Maternal risk score for the prediction of fetal inflammatory response syndrome after preterm premature rupture of membranes.

AIM: Preterm premature rupture of membranes (PPROM) is common in preterm births. Fetal inflammatory response syndrome (FIRS) is present in nearly 50% of PPROM cases. We created a risk score to predict FIRS using maternal factors after PPROM. METHODS: We conducted a retrospective study of singleton pregnancies complicated by PPROM that resulted in delivery at 23-35 weeks of gestation. Antepartum maternal factors and umbilical cord blood interleukin-6 (IL-6) data were analyzed. FIRS was defined as IL-6 > 11 pg/mL. RESULTS: Umbilical cord blood IL-6 and maternal blood data within 24 h before parturition were available for 158 cases; 66 were diagnosed with FIRS (41.8%; median IL-6, 57.55 pg/mL). We created a risk score (FIRS score) comprising expected delivery weeks (≤30 weeks), maternal C-reactive protein (≥1.2 mg/dL), maternal white blood cell count (≥13 000/µL), corticosteroid use (none) and PROM latency period (≥3 days) from the multivariate logistic regression model predicting FIRS. Receiver operating characteristic curve analysis of the score produced the following results: area under the curve, 0.82; 95% CI, 0.76-0.89; cut-off value, 7.5; sensitivity, 89%; specificity, 63%; positive predictive value, 63% and negative predictive value, 89%. The probability of FIRS according to the categories of the FIRS score was 11% for those with a score of 0-7, 50% for a score of 8-15, and 88% for a score of 16-22. CONCLUSION: The devised maternal risk score could predict FIRS and be helpful to decide the delivery timing for the cases of PPROM.

Cerebral dural sinus thrombosis associated with adenomyosis: a case report.

We report a case of cerebral venous thrombosis (CVT) associated with a giant adenomyosis. At admission, the patient demonstrated generalized seizures and consciousness disturbance. Brain fluid-attenuated inversion recovery magnetic resonance imaging revealed a localized, high-intensity region in the left frontal lobe. Subsequent brain angiography showed that right internal carotid angiograms display abrupt termination of the anterior half of the superior sagittal sinus and a filling defect in the lateral part of the left transverse sinus. The patient complicated with iron deficiency anemia (IDA) and adenomyosis with higher levels of serum carbohydrate antigen 125 (CA125) and d-dimer. After 1 year from onset, intermittent severe menalgia and headache persisted, and blood examination revealed abnormal values; the patient was receiving oral medications. Finally, adenomyosis resection was performed with a favorable outcome, and no recurrence was observed during the 2-year follow-up period. We conclude that IDA and increased CA125 levels may have promoted hypercoagulability and CVT. This report emphasizes the possible relationship between CVT and adenomyosis.