Pre-diagnosis Dietary One-Carbon Metabolism Micronutrients Consumption and Ovarian Cancer Survival: A Prospective Cohort Study.

Background and Aims: Epidemiological evidence on the relation between one-carbon metabolism (OCM) micronutrients intake and ovarian cancer (OC) survival are limited and conflicting. We evaluated the aforementioned associations in a prospective cohort-the Ovarian Cancer Follow-Up Study. Methods: A total of 635 newly diagnosed OC patients aged 18-79 y were enrolled in the present study. Dietary intake related to one-carbon metabolism, including methionine, vitamins B2, B3, B6, B9, B12, choline, and betaine, was assessed using a validated 111-item food frequency questionnaire. Deaths were ascertained until March 31, 2021, via medical records and active follow-up. Cox proportional hazards regression model was used to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) for these aforementioned associations. Results: During a median follow-up of 37.2 months (interquartile: 24.7-50.2 months), 114 deaths were identified. We observed an improved survival with the highest compared with the lowest tertile of dietary vitamin B6 (HR = 0.52, 95%CI: 0.32-0.84, P-trend <0.05) and choline intake (HR = 0.50, 95%CI: 0.30-0.83, P-trend <0.05). No significant associations with OC survival were observed for dietary vitamins B2, B3, B9, B12, methionine, and betaine intake. We also observed a curvilinear association between vitamin B6 intake and OC survival (P non-linear <0.05). Conclusion: Our study suggests that pre-diagnosis higher intake of vitamin B6 and choline may improve OC survival. Further clarification of these associations is warranted.

Gynecologists Need to Be Vigilant-Two Case Reports of Intravascular Leiomyomatosis and Literature Review.

BACKGROUND: Intravascular leiomyomatosis is a rare benign lesion with malignant potential. The cases are sporadic. Most patients have no clinical symptoms, and the preoperative diagnostic rate is low. Case 1 was misdiagnosed, passively managed during operation, recurred quickly, and underwent a secondary operation. We learned lessons from case 1 and treated the case 2 patient differently. The case 2 patient had a good prognosis. We hope the report will be helpful to other gynecologists. CASE SUMMARY: Case 1: a 49-year-old woman complained of dysmenorrhea. Traditional ultrasound showed adenomyosis and a solid mass 6 * 3 cm in the right appendix. After routine examination, the patient underwent transabdominal total hysterectomy + bilateral salpingectomy + IVL tumor resection, with both ovaries kept. No medication was used after operation. Routine ultrasound was performed every 3 months. The disease recurred, and the patient underwent a secondary surgery 9 months after the first time. So far, 25 months after the secondary surgery, there is no sign of recurrence. Case 2: a 41-year-old woman underwent a routine body examination, where a left adnexal mass 7 cm was found. The patient underwent contrast-enhanced ultrasonography and was diagnosed and prepared well preoperatively. The patient underwent transabdominal total hysterectomy + bilateral salpingectomy + IVL tumor resection. GnRH-a drugs were used after operation for 3 cycle. Now, there is no sign of recurrence after operation for 23 months. CONCLUSION: The incidence rate of IVL is low, and there are no typical clinical symptoms. It is easy to be ignored by gynecologists. Contrast-enhanced ultrasound is helpful to diagnose preoperatively and reduce misdiagnosis. Good preparation, full exploration of the pelvic and abdominal vessels, removal of lesions completely as much as possible, and anti-estrogen therapy after operation can reduce the recurrence of disease.

Prognostic Influence of the Time Interval between Surgery and Chemotherapy in Epithelial Ovarian Cancer.

The influence of time to chemotherapy (TTC) on recurrence and survival among epithelial ovarian cancer (EOC) patients still remains unknown. This single center retrospective cohort study was conducted on 489 EOC patients who underwent surgery followed by taxane- plus platinum-based chemotherapy in the Shengjing Hospital of China Medical University between 2011 and 2015. The Multivariate cox proportional regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS) after adjustment for potential confounders. The median follow-up duration was 2.97 years (inter-quartile range from 2.11 to 4.13 years). The recurrence and mortality rate of the all patients was 50.9% (249/489) and 43.6% (213/489), respectively. Having comorbidity, residual disease, ascites, and advanced FIGO stage (III-IV) was associated worse PFS and OS of EOC patients. Compared to TTC less than 14 days, delayed TTC (more than 28 days) was associated with a worse PFS (HR=1.36; 95%CI: 0.96-1.92) and OS (HR=1.38; 95%CI: 0.95-2.00). Notably, in EOC patients with advanced stage, delayed TTC (more than 28 days) was associated with worse PFS (HR=1.51; 95%CI: 1.02-2.24) and OS (HR=1.53; 95%CI: 1.01-2.32) when comparing to TTC less than 14 days. In conclusion, delayed TTC was associated with higher rates of EOC recurrence and survival among these patients with advanced stage. The findings of the present study may provide evidence for gynecologist as well as these ovarian cancer patients to make further decision for the treatment.

Comorbidity and survival among women with ovarian cancer: evidence from prospective studies.

The relationship between comorbidity and ovarian cancer survival has been controversial so far. Therefore, we conducted a meta-analysis to summarize the existing evidence from prospective studies on this issue. Relevant studies were identified by searching the PubMed, EMBASE, and ISI Web of Science databases through the end of January 2015. Two authors independently performed the eligibility evaluation and data abstraction. Random-effects models were used to estimate summary hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival. Eight prospective studies involving 12,681 ovarian cancer cases were included in the present study. The summarized HR for presence versus absence of comorbidity was 1.20 (95% CI = 1.11-1.30, n = 8), with moderate heterogeneity (I(2) = 31.2%, P = 0.179). In addition, the summarized HR for the highest compared with the lowest category of the Charlson's comorbidity index was 1.68 (95% CI = 1.50-1.87, n = 2), without heterogeneity (I(2) = 0%, P = 0.476). Notably, a significant negative impact of comorbidity on ovarian cancer survival was observed in most subgroup analyses stratified by the study characteristics and whether there was adjustment for potential confounders. In conclusion, the findings of this meta-analysis suggest that underlying comorbidity is consistently associated with decreased survival in patients with ovarian cancer. Comorbidity should be taken into account when managing these patients.

[Acetylation of hepatic histone H3 in rats with intrauterine growth retardation].

OBJECTIVE: To investigate the effects of intrauterine growth retardation (IUGR) caused by malnutrition during pregnancy on the acetylation of histone H3 and expression of histonedeacetylase1(HDAC1) in the hepar of the adult offspring and to explore the relationship between them. METHODS: Male 8-week-old offspring from maternal protein-malnutrition dams were studied. The expression of HDAC1 mRNA in the hepar was measured by fluorescent quantization RT-PCR. The levels of hepatic nuclear HDAC1 protein and acetylation of histone H3/K9 were assessed by Western blot. RESULTS: The hepatic HDAC1 mRNA expression in IUGR rats was reduced to 54% of that of normal control rats (t=2.042, p<0.05). A decline in nuclear expression of HDAC1 protein (438 +/- 47) was also noted when compared with normal controls (1,128 +/- 110) (t=2.179, p<0.05). In contrast, the percentage of acetylated histone H3/K9 in IUGR rats (17.3 +/- 1.6%) increased significantly compared with that of normal control rats (10.5 +/- 1.2%) (t=3.597, p<0.01). The level of acetylated histone H3/K9 was negatively correlated with the HDAC1 protein concentration (r=-0.781, p<0.01). CONCLUSIONS: Increased hepatic acetylation of histone H3 in the IUGR offspring might be caused by decreased HDAC1 expression in nuclear protein. This may contribute to the transcription change of some genes in the hepar.

[Perturbed hepatic phosphoinositol 3-kinase signaling pathway in the rat with intrauterine growth restriction].

OBJECTIVE: To determine the molecular mechanisms linking intrauterine growth restriction (IUGR) to adult type 2 diabetes mellitus, the effect of IUGR on the hepatic post-receptor insulin-signaling pathway was investigated in the adult offspring. METHODS: The IUGR model was prepared by maternal protein-malnutrition. Western blotting analysis was undertaken to assess hepatic expression of insulin receptor substrate (IRS-2), phosphoinositol 3-kinase (PI-3K), protein kinase B (PKB), phosphorylated PKB-Ser473 and glycogen synthase kinase (GSK) 3 in 8-week-old male IUGR rats. RESULTS: The basal levels of PI-3K protein decreased in IUGR rats compared with normal controls (p<0.01), whereas GSK-3beta protein level significantly increased in IUGR rats (p<0.01). Both PKB and phosphorylated PKB-Ser473 protein levels significantly decreased in the liver of IUGR rats compared with normal controls (p<0.01)). After insulin administration, phosphorylated PKB-Ser473 significantly increased to 182% of basal level in control rats(p<0.01); However, phosphorylation of PKB which responded to insulin was markedly blunted in IUGR rats compared with controls and only increased to 123% of basal level (p<0.05). CONCLUSIONS: The level of PI-3K and PKB and phosphorylated PKB-Ser473 expression decreased in the liver of IUGR rats, whereas the levels of GSK-3beta protein increased. It may contribute to the pathogenesis of insulin resistance in the IUGR rats.