Patient reported outcomes after risk-reducing surgery in patients at increased risk of ovarian cancer.

OBJECTIVE: To describe the quality of life of women at an increased risk of ovarian cancer undergoing risk-reducing bilateral salpingo-oophorectomy (RRBSO). METHODS: Patients evaluated in our gynecologic oncology ambulatory practice between January 2018-December 2019 for an increased risk of ovarian cancer were included. Patients received the EORTC QLQ-C30 and PROMIS emotional and instrumental support questionnaires along with a disease-specific measure (PROM). First and last and pre- and post-surgical PROM responses in each group were compared as were PROMs between at-risk patients and patients with other ovarian diseases. RESULTS: 195 patients with an increased risk of ovarian cancer were identified, 155 completed PROMs (79.5%). BRCA1 or BRCA2 mutations were noted in 52.8%. Also included were 469 patients with benign ovarian disease and 455 with ovarian neoplasms. Seventy-two at-risk patients (46.5%) had surgery and 36 had both pre- and post-operative PROMs. Post-operatively, these patients reported significantly less tension (p = 0.011) and health-related worry (p = 0.021) but also decreased levels of health (p = 0.018) and quality of life <7d (0.001), less interest in sex (p = 0.014) and feeling less physically attractive (p = 0.046). No differences in body image or physical/sexual health were noted in at-risk patients who did not have surgery. When compared to patients with ovarian neoplasms, at-risk patients reported lower levels of disease-related life interference and treatment burden, less worry, and better overall health. CONCLUSIONS: In patients with an increased risk of ovarian cancer, RRBSO is associated with decreased health-related worry and tension, increased sexual dysfunction and poorer short-term quality of life. Patients with ovarian neoplasms suffer to a greater extent than at-risk patients and report higher levels of treatment burden and disease-related anxiety.

Effect of surgical approach on risk of recurrence after vaginal brachytherapy in early-stage high-intermediate risk endometrial cancer.

OBJECTIVE: The objective was to determine if surgical approach affects time to recurrence in early-stage high-intermediate risk endometrial cancer (HIR-EC) treated with adjuvant vaginal brachytherapy (VBT). METHODS: In this retrospective cohort study, HIR-EC patients treated with VBT between 2005 and 2017 were identified and those who received open or minimally invasive hysterectomies (MIS) were included. Clinical and surgical variables were analyzed and time to recurrence was compared between surgical groups. RESULTS: We identified 494 patients, of which 363 had MIS hysterectomies, 92.5% had endometrioid histology, 45.7% were stage IA and 48.0% stage IB. Open hysterectomy patients had higher BMIs (p = 0.007), lower rates of lymph node sampling (p < 0.001) and lymphovascular space invasion (LVSI) (p = 0.036), however in patients who recurred, no differences were noted between groups. Overall, 65 patients (13.2%) recurred, 14 in the open group (10.7%) and 51 in the MIS group (14.0%) (p = 0.58), while vaginal recurrences were noted in 4.6% and 6.1% respectively. When compared to the open group, the MIS group had a significantly shorter time to any recurrence (p = 0.022), to pelvic (p = 0.05) and locoregional recurrence (p = 0.021) and to death from any cause (p = 0.039). After adjusting for age, BMI, grade, LVSI and surgery date, the MIS group had a higher risk of any recurrence (HR 2.29 (1.07-4.92), p = 0.034) and locoregional recurrence (HR 4.18 (1.44-12.1), p = 0.008). CONCLUSIONS: Patients with HIR-EC treated with VBT after MIS hysterectomy have a shorter time to recurrence and higher risk of recurrence when compared to open hysterectomy patients. Further studies into the safety of MIS in high-intermediate risk patients are required.

Lymphadenectomy for high-grade endometrial cancer: Does it impact lymph node recurrence?

INTRODUCTION: The diagnostic role of lymph node (LN) assessment is established in endometrial cancer. Our study assesses whether surgical removal of metastatic LNs has oncologic benefit in high-grade endometrial cancer. MATERIALS AND METHODS: High-grade endometrial cancer cases (2000-2010) were collected from two tertiary cancer centres. In patients with at least one positive LN, recurrence free survival (RFS) was compared by the number of LNs removed. Factors predicting nodal recurrence (NR) were explored. Univariate statistical analyses by log rank test and multivariable cox proportional hazards model were performed using SAS version 9.4. RESULTS: Of 570 patients identified, 334 patients underwent staging lymphadenectomy, 74 (22.2%) patients had at least one positive LN. The median RFS with at least one positive lymph node was 87.1 months (95% CI ≥ 14.3) when greater than 15 LNs were removed, compared to 16.9 months (95% CI, 13.6-35.6) and 17.3 months (95% CI, 8.5-39.8) when 5-15 and less than 5 LNs were removed, respectively (p = 0.02). In the cohort of 570 patients, there were 167 disease recurrences with location described on imaging, 98 (58.7%) had a NR and 69 (41.3%) recurred at other sites. Multivariable modeling identified that only positive LNs at surgical staging predicted NR (HR 3.8, 95% CI 1.4-10.2). CONCLUSION: In high-grade endometrial cancer, positive LNs predict NR, and RFS is longer with a more extensive LN dissection in women with positive LNs. Future prospective studies should evaluate the oncologic benefit of surgical removal of metastatic LNs in high-grade endometrial cancer.

The use of neoadjuvant chemotherapy in advanced endometrial cancer.

The objective of this retrospective cohort study was to review the use of neoadjuvant chemotherapy followed by interval cytoreductive surgery in patients presenting with advanced, unresectable endometrial cancer at two large cancer centers. Patients with advanced endometrial cancer treated with neoadjuvant chemotherapy between 2008 and 2015 were identified from an institutional database. Clinical and surgical variables were analyzed and time to recurrence and death was calculated and compared between surgical groups. Thirty-three patients were identified (mean age 64.8 (range 42-86 years)). Overall, 28% of patients had endometrioid histology, 48% serous, 4% clear cell, 4% carcinosarcoma, 12% mixed and 4% other. Ineligibility for primary surgery was due to unresectable disease (85%), comorbidities (6%) and unknown reasons (9%). All patients received neoadjuvant chemotherapy with 91% of patients receiving carboplatin and paclitaxel. On reimaging, 12% of patients had progressed, 76% had a partial response and 3% had a complete response to chemotherapy. 76% of patients underwent interval surgery, with cytoreduction to no visible residual disease achieved in 52%. Overall, 91% of patients recurred and 85% died during follow-up. Patients undergoing surgery after chemotherapy had significantly longer progression-free survival (11.53 vs. 4.99 months, p = 0.0096) and overall survival (24.13 vs. 7.04 months, p = 0.0042) when compared to patients who did not have surgery. Neoadjuvant chemotherapy is a feasible treatment option to allow for interval cytoreductive surgery in patients with advanced endometrial cancer not amenable to primary debulking. Patients who undergo surgery after chemotherapy have significantly improved progression free and overall survival.

A challenging case of twin pregnancy with complete hydatidiform mole and co-existing normal live fetus - A case report and review of the literature.

Hydatidiform mole coexisting with a normal live fetus in a twin pregnancy is extremely rare. Management of these cases is challenging due to the risk of severe antepartum and post-partum complications. Herein, we report the case of a 24-year-old gravida 2 para 1 who presented at 28 weeks gestation with severe preeclampsia, vulvar edema and a serum ß-HCG of 285,000 IU/mL. Ultrasonography demonstrated a single live intra-uterine pregnancy with concurrent hydatidiform mole. Conservative management with magnesium sulfate and anti-hypertensive medications was initiated however the patient developed HELLP syndrome and required urgent delivery at 33 weeks. Copious molar tissue was removed from the uterus during delivery. Four weeks post-partum, her ß-HCG had dropped to 14,000 IU/ml and continued to decline at 6 weeks (2900 IU/ml). However, at eight weeks, it increased to 3500 IU/ml and the patient was treated with nine cycles of intramuscular methotrexate. Current guidelines for management of a twin pregnancy with coexistent mole recommend close clinical monitoring if the mother and fetus are stable and urgent delivery in the setting of complications. During the postpartum period, careful follow up with clinical evaluation and serial serum ß-HCG is important for the diagnosis and treatment of persistent trophoblastic disease.

The rapid chemically induced corrosion of concrete sewers at high H2S concentration.

Concrete corrosion in sewers is primarily caused by H2S in sewer atmosphere. H2S concentration can vary from several ppm to hundreds of ppm in real sewers. Our understanding of sewer corrosion has increased dramatically in recent years, however, there is limited knowledge of the concrete corrosion at high H2S levels. This study examined the corrosion development in sewers with high H2S concentrations. Fresh concrete coupons, manufactured according to sewer pipe standards, were exposed to corrosive conditions in a pilot-scale gravity sewer system with gaseous H2S at 1100 ±â€¯100 ppm. The corrosion process was continuously monitored by measuring the surface pH, corrosion product composition, corrosion loss and the microbial community. The surface pH of concrete was reduced from 10.5 ±â€¯0.3 to 3.1 ±â€¯0.5 within 20 days and this coincided with a rapid corrosion rate of 3.5 ±â€¯0.3 mm year -1. Microbial community analysis based on 16S rRNA gene sequencing indicated the absence of sulfide-oxidizing microorganisms in the corrosion layer. The chemical analysis of corrosion products supported the reaction of cement with sulfuric acid formed by the chemical oxidation of H2S. The rapid corrosion of concrete in the gravity pipe was confirmed to be caused by the chemical oxidation of hydrogen sulfide at high concentrations. This is in contrast to the conventional knowledge that is focused on microbially induced corrosion. This first-ever systematic investigation shows that chemically induced oxidation of H2S leads to the rapid corrosion of new concrete sewers within a few weeks. These findings contribute novel understanding of in-sewer corrosion processes and hold profound implications for sewer operation and corrosion management.

Maternal overnutrition suppresses the phosphorylation of 5'-AMP-activated protein kinase in liver, but not skeletal muscle, in the fetal and neonatal sheep.

Epidemiological studies have shown that infants exposed to an increased supply of nutrients before birth are at increased risk of type 2 diabetes in later life. We have investigated the hypothesis that fetal overnutrition results in reduced expression and phosphorylation of the cellular fuel sensor, AMP-activated kinase (AMPK) in liver and skeletal muscle before and after birth. From 115 days gestation, ewes were fed either at or approximately 55% above maintenance energy requirements. Postmortem was performed on lamb fetuses at 139-141 days gestation (n = 14) and lambs at 30 days of postnatal age (n = 21), and liver and quadriceps muscle were collected at each time point. The expression of AMPKalpha1 and AMPKalpha2 mRNA was determined by quantitative RT-PCR (qRT-PCR). The abundance of AMPKalpha and phospho-AMPKalpha (P-AMPKalpha) was determined by Western blot analysis, and the proportion of the total AMPKalpha pool that was phosphorylated in each sample (%P-AMPKalpha) was determined. The ratio of AMPKalpha2 to AMPKalpha1 mRNA expression was lower in fetuses compared with lambs in both liver and muscle, independent of maternal nutrition. Hepatic %P-AMPKalpha was lower in both fetuses and lambs in the Overfed group and %P-AMPKalpha in the lamb liver was inversely related to plasma glucose concentrations in the first 24 h after birth (r = 0.73, P < 0.025). There was no effect of maternal overnutrition on total AMPKalpha or P-AMPKalpha abundance in liver or skeletal muscle. We have, therefore, demonstrated that AMPKalpha responds to signals of increased nutrient availability in the fetal liver. Suppression of hepatic AMPK phosphorylation may contribute to increased glucose production, and basal hyperglycemia, present in lambs of overfed ewes in early postnatal life.

Lymphatic cysts of the colon.

A patient with a lymphatic cyst of the descending colon is reported. He underwent segmental resection of the colon. The clinical features, pathology, radiology, and treatment of these lesions are reviewed. It is emphasized that these cysts are very rare and cannot be diagnosed radiologically, but must be included in the differential diagnosis of polypoid lesions of the colon.

Heterogeneity of hepatitis C virus genotypes in hemophilia: relationship with chronic liver disease.

In this study we have determined the hepatitis C virus (HCV) serotype and genotype in a cohort of 96 HCV-infected hemophiliacs and have examined the relationship between HCV genotype and severity of chronic liver disease as determined by liver biopsy. HCV serotype was determined by specific enzyme-linked immunosorbent assays (ELISAs) and genotype by restriction fragment length polymorphism (RFLP) and HCV viral sequencing. The pattern of genotype distribution was quite unlike that of HCV-infected United Kingdom (UK) blood donors in that five of the six known HCV genotypes were represented, 50% were type 1, 13% type 2, and 18% type 3. An unexpected observation was the presence of HCV genotype 4 in four patients and type 5 in two patients. An additional feature was the presence of mixed infection, detected in 14% and 7% by serotype and genotype analysis, respectively. Liver biopsies were available from 51 patients. Cirrhosis was present in five of 27 (19%) of individuals with type 1, in 2 of 9 (22%) with type 2, and 5 of 8 (63%) of those with type 3. The heterogeneous pattern of HCV genotype distribution in this cohort of patients and the observed relationship between the severity of the related liver disease and specific HCV genotype may have important implications with respect to the natural history and treatment of HCV-related chronic liver disease in infected hemophiliacs worldwide.