Biological Insights into Chemotherapy Resistance in Ovarian Cancer.

The majority of patients with high-grade serous ovarian cancer (HGSOC) initially respond to chemotherapy; however, most will develop chemotherapy resistance. Gene signatures may change with the development of chemotherapy resistance in this population, which is important as it may lead to tailored therapies. The objective of this study was to compare tumor gene expression profiles in patients before and after treatment with neoadjuvant chemotherapy (NACT). Tumor samples were collected from six patients diagnosed with HGSOC before and after administration of NACT. RNA extraction and whole transcriptome sequencing was performed. Differential gene expression, hierarchical clustering, gene set enrichment analysis, and pathway analysis were examined in all of the samples. Tumor samples clustered based on exposure to chemotherapy as opposed to patient source. Pre-NACT samples were enriched for multiple pathways involving cell cycle growth. Post-NACT samples were enriched for drug transport and peroxisome pathways. Molecular subtypes based on the pre-NACT sample (differentiated, mesenchymal, proliferative and immunoreactive) changed in four patients after administration of NACT. Multiple changes in tumor gene expression profiles after exposure to NACT were identified from this pilot study and warrant further attention as they may indicate early changes in the development of chemotherapy resistance.

Postoperative readmissions following ileostomy formation among patients with a gynecologic malignancy.

OBJECTIVES: Ileostomy results in a relatively poorer water reabsorption and is associated with dehydration and renal injury. These problems may be exacerbated in the setting of gynecologic cancers owing to both patient and disease-related factors. We evaluated the rate and reasons for hospital readmission within 30 days of ileostomy creation in patients with a gynecologic malignancy. METHODS: We performed a retrospective review of women with gynecologic malignancies who underwent ileostomy creation between 2002 and 2013. RESULTS: Fifty-three patients were eligible for analysis. The mean age was 63.3 years. Most patients had ovarian cancer (86.5%). Indications for ileostomy included small bowel obstruction (45.3%), as part of primary debulking (18.9%), or treatment of an anastomotic leak (15.1%). The 30-day readmission rate was 34%. Co-morbid diseases such as hypertension (p=0.008) and chronic kidney disease (p=0.010) were more common among women who were readmitted. The most common reasons for readmission were dehydration (38.9%) and acute renal failure (33.3%); women readmitted for these conditions had higher average serum creatinine levels at initial postoperative discharge (1.00 mg/dL versus 0.71 mg/dL, p=0.017) than women who did not require readmission. Readmitted women had a trend toward shorter overall survival (0.41 years versus 1.67 years, p=0.061). CONCLUSIONS: Readmission rates for gynecologic oncology patients undergoing ileostomy were similar to, but higher than those previously reported in the colorectal literature. In our population, patients with preexisting cardiovascular or renal disease were at the highest risk of readmission and may benefit from preemptive strategies to decrease high ostomy output and dehydration.

Neoadjuvant chemotherapy (NACT) is an effective way of managing elderly women with advanced stage ovarian cancer (FIGO Stage IIIC and IV).

BACKGROUND: To compare outcomes in women ≥ age 70 who receive neoadjuvant chemotherapy (NACT) for advanced epithelial ovarian cancer (EOC) followed by cytoreductive surgery with those undergoing upfront cytoreductive surgery followed by the same chemotherapy. METHODS: A retrospective cohort study was performed for women ≥ age 70 with Stage IIIC or Stage IV EOC from 1996 to 2009. RESULTS: Sixty-two patients who underwent upfront cytoreductive surgery and 42 patients who received NACT were eligible for analysis. Patients receiving NACT were significantly more likely to have Stage IV disease (P = 0.004). Cytoreduction to no macroscopic disease was achieved in 71.4% of women who received NACT and 28.1% of women undergoing upfront surgery (P < 0.001). NACT patients had significantly less blood loss at surgery (P = 0.01), required fewer small bowel resections (P = 0.009), had shorter ICU stays (P = 0.02) and fewer hospital days (P = 0.04). NACT patients experienced a trend toward an improved progression-free survival (P = 0.078); however, no statistically significant differences were found in either the progression-free or overall survival analyses. CONCLUSION: NACT is associated with reduced perioperative morbidity in elderly patients with advanced stage ovarian cancer.

Impact of age on preoperative and postoperative urinary incontinence quality of life.

OBJECTIVE: The objective of the study was to estimate the effect of age on quality of life in women with urinary incontinence before and following antiincontinence surgery. STUDY DESIGN: We performed a retrospective cohort study of women who underwent surgery for stress urinary incontinence from December 2003 to August 2005. Younger women were defined as age younger than 60 years and older women were defined as age 60 years or older. Quality of life was measured using Incontinence Impact Questionnaire (IIQ)-7 and Urogenital Distress Inventory (UDI)-6 questionnaires pre- and postoperatively. Multiple linear regression was performed to estimate the effect of age on improvement in quality-of-life scores. RESULTS: One hundred sixty-eight younger women and 81 older women were included. Older women had lower mean baseline IIQ-7 scores (P < .01) and had less improvement in IIQ-7 scores postoperatively (P = .02) when compared with younger women. After adjusting for baseline IIQ-7 score using multiple linear regression, age was no longer associated with decreasing improvements in quality-of-life scores following surgical treatment. CONCLUSIONS: Antiincontinence surgery is associated with improved quality of life in both older and younger women.