BRCA carriers after risk-reducing bilateral salpingo-oophorectomy: menopausal hormone therapy knowledge gaps, and the impact of physicians' recommendations.

OBJECTIVE: Female carriers of BRCA1/2 gene mutations are at an increased lifetime risk for breast and ovarian cancers. They are recommended to undergo risk-reducing surgery, including bilateral salpingo-oophorectomy (RR-BSO), upon completion of childbearing. RR-BSO surgery decreases morbidity and mortality but results in early menopause. Menopausal hormone therapy (MHT) is under-utilized despite being shown as safe for carriers. We aim to evaluate the factors associated with decision-making regarding MHT use following RR-BSO in healthy BRCA mutation carriers. METHODS: Female carriers aged <50 years who underwent RR-BSO and were followed in a multidisciplinary clinic completed online multiple-choice and free-text questionnaires. RESULTS: A total of 142 women met the inclusion criteria and filled the questionnaire: 83 were MHT users and 59 were non-users. MHT users underwent RR-BSO earlier than non-users (40.82 ± 3.91 vs. 42.88 ± 4.34; p < 0.0001). MHT usage was positively associated with MHT explanation (odds ratio 4.318, 95% confidence interval [CI] [1.341-13.902], p = 0.014), and knowledge regarding the safety of MHT and its effects on general health (odds ratio 2.001, 95% CI [1.443-2.774], p < 0.0001). MHT users and non-users retrospectively evaluated their comprehension of RR-BSO consequences as significantly lower than before surgery (p < 0.001). CONCLUSION: Post-RR-BSO outcomes, including the effects on women's quality of life and its possible mitigation through MHT use, need to be addressed pre surgery by healthcare providers.

Association between autophagy and KRAS mutation with clinicopathological variables in colorectal cancer patients.

Autophagy is a host defensive mechanism responsible for eliminating harmful cellular components through lysosomal degradation. Autophagy has been known to either promote or suppress various cancers including colorectal cancer (CRC). KRAS mutation serves as an important predictive marker for epidermal growth factor receptor (EGFR)-targeted therapies in CRC. However, the relationship between autophagy and KRAS mutation in CRC is not well-studied. In this single-centre study, 92 formalin-fixed paraffin-embedded (FFPE) tissues of CRC patients (42 Malaysian Chinese and 50 Indonesian) were collected and KRAS mutational status was determined by quantitative PCR (qPCR) (n=92) while the expression of autophagy effector (p62, LC3A and LC3B) was examined by immunohistochemistry (IHC) (n=48). The outcomes of each were then associated with the clinicopathological variables (n=48). Our findings demonstrated that the female CRC patients have a higher tendency in developing KRAS mutation in the Malaysian Chinese population (p<0.05). Expression of autophagy effector LC3A was highly associated with the tumour grade in CRC (p<0.001) but not with other clinicopathological parameters. Lastly, the survival analysis did not yield a statistically significant outcome. Overall, this small cohort study concluded that KRAS mutation and autophagy effectors are not good prognostic markers for CRC patients.

High expression of LC3A, LC3B, and p62/SQSTM1 autophagic proteins in human colonic ganglion cells.

INTRODUCTION: Autophagy is a mechanism that degrades large damaged organelles and misfolded proteins to maintain the homeostasis in all cells. It plays double-faceted roles in tumourigenesis and prevention of various cancers. In our side observation of investigating the prognostic value of autophagy in colorectal cancer (CRC), we found high expression of autophagy proteins (LC3A, LC3B, and p62/SQSTM1) in the colonic ganglion cells. To our best understanding, this is the first paper reporting such finding. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded (FFPE) CRC tissues blocks were retrieved and confirmed by haematoxylin & eosin (H&E) staining. Immunohistochemistry (IHC) targeting autophagy proteins (LC3A, LC3B, and p62/SQSTM1) was then performed followed by pathological examination. RESULTS: All three autophagy proteins were present in both normal and tumour tissues of CRC patients. Interestingly, high expression of autophagy proteins in colonic ganglion cells was consistently seen regardless of tissue type (normal or cancer) or tumour site (caecum, ascending, transverse, descending, sigmoid colon and rectum). CONCLUSIONS: This work highlights the high autophagic activities in human colonic ganglion cells.

Ovarian clear cell carcinoma recurrence presenting as subcutaneous nodules.

Skin metastasis is a rare form of ovarian carcinoma spread and is associated with widespread disease and a poor prognosis. The authors present a case of a patient, with a past history of ovarian clear cell carcinoma, who presented with subcutaneous nodules as the first sign of recurrent metastatic disease.

Early second trimester transvaginal ultrasound anomaly scan does not cause adverse perinatal outcome.

OBJECTIVE: During an early second-trimester transvaginal ultrasound anomaly scan, pressure is applied to the uterus, and the fetus is often rotated manually to allow scanning of its various organs. This study was designed to determine if performing a transvaginal ultrasound anomaly scan during the early second trimester of pregnancy is associated with adverse perinatal outcome or cord entanglement. METHODS: During the 4.5year study period we prospectively collected cases of routine ultrasound scans at 14-17weeks gestation performed as anomaly screening, together with perinatal outcome. The study population consisted of 164 women who underwent a transvaginal approach, and the control population consisted of 224 women in which a transabdominal approach was used. Data on perinatal parameters was collected from delivery charts from the four local hospitals. RESULTS: There were more operative deliveries (vaginal or Cesarean) in the transvaginal scan group (32% vs. 23%, p=0.05). However, on multiple logistic regression analysis vaginal scans were not associated with increased operative delivery rates with an adjusted odds ratio of 1.47 and a 95% confidence interval of 0.85-2.54. There were no other clinically significant differences in perinatal outcomes, or in cord entanglement. CONCLUSIONS: Transvaginal ultrasound anomaly scan conducted in the early second trimester of pregnancy is a safe procedure for the fetus.

Severe heart disease complicating pregnancy does not preclude a favourable pregnancy outcome: 15 years' experience in a single centre.

Heart disease (HD) in pregnancy remains a major cause of non-obstetric maternal and neonatal mortality and morbidity. This study describes the outcome in 164 pregnant women with HD (158 deliveries in women in New York Heart Association (NYHA) Classes 1 and 2; 17 in NYHA Classes 3 and 4) who received good antenatal care and benefitted from a specific protocol and experience of a dedicated staff. There were no maternal or neonatal deaths; 46 women were diagnosed peripartum. Based on a sub-division into NYHA categories, and when sub-divided by HD, there were no statistically significant differences between groups with regard to maternal age, gestational age at admission or at delivery, birth weight, 5 min Apgar scores, mode of delivery (caesarean delivery), senior obstetric/anaesthesiology staff in attendance or delivery during day/working hours. There was a higher incidence of pre-term deliveries in women with rheumatic heart disease and Marfan syndrome (p = 0.06) relative to others. Babies of women with coronary heart disease had prolonged postpartum course in the NICU (p = 0.0001) and longer total hospital stays for the mother. In conclusion, well-managed, motivated mothers with HD who benefit from comprehensive antenatal care, and are managed primarily by their obstetric and anaesthesia teams, can aspire to a good outcome for themselves and their babies.

Large-cell lymphoma presenting as acute cholecystitis.

A 62-year-old woman presenting with a clinical picture of acute cholecystitis was found to have lymphoma upon pathological examination of the gallbladder. Such a presentation of large-cell non-Hodgkin's lymphoma is unique and has not been described before.

Nifedipine-induced hypokalemia.

Nifedipine, a calcium-channel blocking agent, has been reported to cause many side effects, particularly in the cardiovascular system. A case of nifedipine-induced hypokalemia is presented, with a discussion on the presumable mechanism involved in this phenomenon.