Eleftheria Kalogera

Enhanced recovery in gynecologic surgery.

OBJECTIVE: To investigate the effects of enhanced recovery (a multimodal perioperative care enhancement protocol) in patients undergoing gynecologic surgery. METHODS: Consecutive patients managed under an enhanced recovery pathway and undergoing cytoreduction, surgical staging, or pelvic organ prolapse surgery between June 20, 2011, and December 20, 2011, were compared with consecutive historical controls (March to December 2010) matched by procedure. Wilcoxon rank-sum, &khgr;2, and Fisher’s exact tests were used for comparisons. Direct medical costs incurred in the first 30 days were obtained from the Olmsted County Healthcare Expenditure and Utilization Database and standardized to 2011 Medicare dollars. RESULTS: A total of 241 enhanced recovery women in the case group (81 cytoreduction, 84 staging, and 76 vaginal surgery) were compared with women in the control groups. In the cytoreductive group, patient-controlled anesthesia use decreased from 98.7% to 33.3% and overall opioid use decreased by 80% in the first 48 hours with no change in pain scores. Enhanced recovery resulted in a 4-day reduction in hospital stay with stable readmission rates (25.9% of women in the case group compared with 17.9% of women in the control group) and 30-day cost savings of more than

Correlation of Serum HE4 with Tumor Size and Myometrial Invasion in Endometrial Cancer

7,600 per patient (18.8% reduction). No differences were observed in rate (63% compared with 71.8%) or severity of postoperative complications (grade 3 or more: 21% compared with 20.5%). Similar, albeit less dramatic, improvements were observed in the other two cohorts. Ninety-five percent of patients rated satisfaction with perioperative care as excellent or very good. CONCLUSIONS: Implementation of enhanced recovery was associated with acceptable pain management with reduced opioids, reduced length of stay with stable readmission and morbidity rates, good patient satisfaction, and substantial cost reductions. LEVEL OF EVIDENCE: II

Multiple large bowel resections: Potential risk factor for anastomotic leak☆☆☆

OBJECTIVE To evaluate the utility of serum (HE4) as a marker for high risk disease in patients with endometrial cancer (EC). METHODS Preoperative serum HE4 levels were measured from a cohort of 75 patients surgically treated for EC. Cases were compared to matched controls without a history of cancer. HE4 levels were analyzed as a function of primary tumor diameter, grade, stage and histological subtype. Wilcoxon rank-sum test, ROC curve, Spearman rank correlation coefficient and contingency tables were used for statistical analyses. RESULTS Stage distribution was as follows: 49 stage I, 2 stage II, 20 stage III, 4 stage IV. Type I EC was present in 54 patients, type II in 21. Median HE4 was significantly elevated in both types I and II EC compared to controls (P<0.001 and P=0.019, respectively). There was significant correlation between type I EC, median HE4, deep myometrial invasion (MI) (>50%, P<0.001) and primary tumor diameter (PTD) (>2 cm, P=0.002). Low risk patients (type I, MI ≤ 50% and PTD ≤ 2 cm) had significantly lower median HE4 compared to all other type I EC patients (P<0.01). In comparison to prior investigations, HE4 (cutoff of 8 mfi) was more sensitive than CA125 in detecting advanced stage disease. CONCLUSION Our data suggest that HE4 is elevated in a high proportion of EC patients, is correlated with PTD and MI, and is more sensitive than CA125 in EC. These observations suggest potential utility of HE4 in the preoperative prediction of high risk disease and the necessity for definitive surgical staging.

Preserving fertility in young patients with endometrial cancer: current perspectives

OBJECTIVES Identify risk factors of anastomotic leak (AL) after large bowel resection (LBR) for ovarian cancer (OC) and compare outcomes between AL and no AL. METHODS All cases of AL after LBR for OC between 01/01/1994 and 05/20/2011 were identified and matched 1:2 with controls for age (±5 years), sub-stage (IIIA/IIIB; IIIC; IV), and date of surgery (±4 years). Patient-specific and intraoperative risk factors, use of protective stomas, and outcomes were abstracted. A stratified conditional logistic regression model was fit to determine the association between each factor and AL. RESULTS 42 AL cases were evaluable and matched with 84 controls. Two-thirds of the AL had stage IIIC disease and >90% of both cases and controls were cytoreduced to <1cm residual disease. No patient-specific risk factors were associated with AL (pre-operative albumin was not available for most patients). Rectosigmoid resection coupled with additional LBR was associated with AL (OR=2.73, 95% CI 1.13-6.59, P=0.025), and protective stomas were associated with decreased risk of AL (0% vs. 10.7%, P=0.024). AL patients had longer length of stay (P<0.001), were less likely to start chemotherapy (P=0.020), and had longer time to chemotherapy (P=0.007). Cases tended to have higher 90-day mortality (P=0.061) and were more likely to have poorer overall survival (HR=2.05, 95% CI 1.18-3.57, P=0.011). CONCLUSIONS Multiple LBRs appear to be associated with increased risk of AL and protective stomas with decreased risk. Since AL after OC cytoreduction significantly delays chemotherapy and negatively impacts survival, surgeons should strongly consider temporary diversion in selected patients (poor nutritional status, multiple LBRs, previous pelvic radiation, very low anterior resection, steroid use).

Enhanced Recovery Pathway in Gynecologic Surgery: Improving Outcomes Through Evidence-Based Medicine

Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries and affects predominantly postmenopausal women. It is estimated, however, that 15%–25% of women will be diagnosed before menopause. As more women choose to defer childbearing until later in life, the feasibility and safety of fertility-sparing EC management have been increasingly studied. Definitive treatment of total hysterectomy and bilateral salpingo-oophorectomy precludes future fertility and may thus be undesirable by women who wish to maintain their reproductive potential. However, the consideration of conservative management carries the oncologic risks of unstaged EC and the risk of missing a synchronous ovarian cancer. It is further complicated by the lack of consensus regarding the initial assessment, treatment, and surveillance. Conservative treatment with progestins has been shown to be a feasible and safe fertility-sparing approach for women with low grade, early stage EC with no myometrial invasion. The two most commonly adopted regimens are medroxyprogesterone acetate at 500–600 mg daily and megestrol acetate at 160 mg daily for a minimum of 6–9 months, with initial response rates commonly reported between 60% and 80% and recurrence rates between 25% and 40%. Photodynamic therapy and hysteroscopic EC excision have recently been reported as alternative approaches to progestin therapy alone. However, limited efficacy and safety data exist. Live birth rates after progestin therapy have typically been reported around 30%; however, when focusing only on those who do pursue fertility after successful treatment, the live birth rates were found to be higher than 60%. Assisted reproductive technology has been associated with a higher live birth rate compared with spontaneous conception, most likely reflecting the presence of infertility at baseline. Close follow-up is of paramount importance, and definitive treatment after completion of childbearing is advised.

HE4 Transcription- and Splice Variants-Specific Expression in Endometrial Cancer and Correlation with Patient Survival

A paucity of data exists regarding traditional perioperative practices (bowel preparation, NPO at midnight, liberal narcotics, PCA use, liberal fluids, prolonged bowel and bed rest). Enhanced Recovery after Surgery (ERAS) is an evidence-based approach to peri-operative care associated with improved outcomes including earlier return of gastrointestinal function, reduced opioid use, shorter hospital stay, and substantial cost reductions with stable complication and readmission rates. Basic principles include patient education, minimizing preoperative fasting, avoiding bowel preparation, preemptive analgesia, nausea/vomiting prophylaxis, perioperative euvolemia, no routine use of drain and nasogastric tubes, early mobilization, oral intake, and catheter removal, non-opioid analgesics, and preemptive laxatives.

Safety of culdotomy as a surgical approach: implications for natural orifice transluminal endoscopic surgery.

We investigated the HE4 variant-specific expression patterns in various normal tissues as well as in normal and malignant endometrial tissues. The relationships between mRNA variants and age, body weight, or survival are analyzed. ICAT-labeled normal and endometrial cancer (EC) tissues were analyzed with multidimensional liquid chromatography followed by tandem mass spectrometry. Levels of HE4 mRNA variants were measured by real-time PCR. Mean mRNA levels were compared among 16 normal endometrial samples, 14 grade 1 and 14 grade 3 endometrioid EC, 15 papillary serous EC, and 14 normal human tissue samples. The relationship between levels of HE4 variants and EC patient characteristics was analyzed with the use of Pearson correlation test. We found that, although all five HE4 mRNA variants are detectable in normal tissue samples, their expression is highly tissue-specific, with epididymis, trachea, breast and endometrium containing the highest levels. HE4-V0, -V1, and -V3 are the most abundant variants in both normal and malignant tissues. All variants are significantly increased in both endometrioid and papillary serous EC, with higher levels observed in grade 3 endometrioid EC. In the EC group, HE4-V1, -V3, and -V4 levels inversely correlate with EC patient survival, whereas HE4-V0 levels positively correlate with age. HE4 variants exhibit tissue-specific expression, suggesting that each variant may exert distinct functions in normal and malignant cells. HE4 levels appear to correlate with EC patient survival in a variant-specific manner. When using HE4 as a biomarker for EC management, the effects of age should be considered.

Abdominal Incision Injection of Liposomal Bupivacaine and Opioid Use After Laparotomy for Gynecologic Malignancies.

Data from this study support the feasibility and safety of utilizing the cul-de-sac as an access port to the peritoneal cavity for natural orifice transluminal endoscopic surgery.

Utility of closed suction pelvic drains at time of large bowel resection for ovarian cancer

OBJECTIVE: To investigate opioid use and pain scores associated with incisional injection of liposomal bupivacaine compared with bupivacaine hydrochloride after laparotomy for gynecologic malignancies. METHODS: A retrospective cohort study was conducted to compare abdominal incision infiltration with liposomal bupivacaine with bupivacaine hydrochloride after modification of a pre-existing enhanced recovery pathway. Patients undergoing staging laparotomy or complex cytoreductive surgery under the updated pathway were compared with patients treated under the original pathway (historic controls). Endpoints included cumulative opioid use (primary outcome) in oral morphine equivalents and cumulative pain score. RESULTS: In the complex cytoreductive cohort, median oral morphine equivalents were lower in the liposomal bupivacaine group through 24 hours (30 compared with 53.5 mg, P=.002), 48 hours (37.5 compared with 82.5 mg, P=.005), and the length of stay (62 compared with 100.5 mg, P=.006). Fewer liposomal bupivacaine patients required intravenous rescue opioids (28.9% compared with 55.6%, P<.001) or patient-controlled analgesia (4.1% compared with 33.3%, P<.001). Cumulative pain score was no different between groups through 48 hours (161 compared with 158, P=.69). Postoperative nausea and ileus were less frequent in patients receiving liposomal bupivacaine. Median hospital stay was 5 days in both groups. In the staging laparotomy cohort, cumulative opioids and cumulative pain score were no different between groups (through 48 hours: 162 compared with 161, P=.62; 38 compared with 38, P=.68, respectively). Intravenous rescue opioids (15.3% compared with 28.6%, P=.05) and patient-controlled analgesia (1.4% compared with 8.3%, P=.05) were used less frequently in the liposomal bupivacaine group. Median hospital stay was 4 days in both groups. Despite the higher cost of liposomal bupivacaine, total pharmacy costs did not differ between groups. CONCLUSION: Abdominal incision infiltration with liposomal bupivacaine was associated with less opioid and patient-controlled analgesia use with no change in pain scores compared with bupivacaine hydrochloride after complex cytoreductive surgery for gynecologic malignancies. Improvements were also seen in patients undergoing staging laparotomy.

Quinacrine promotes autophagic cell death and chemosensitivity in ovarian cancer and attenuates tumor growth

OBJECTIVE To test the hypothesis that the use of closed suction pelvic drains placed at time of large bowel resection (LBR) for ovarian cancer (OC) decreases morbidity following anastomotic leak (AL). METHODS Consecutive cases of LBR for OC between 01/01/1994 and 06/20/2011 were retrospectively identified. Drains were routinely used until bowel movement. AL was defined as: 1) feculent fluid from drains/wound/vagina, 2) radiographic evidence of AL, or 3) AL found at reoperation. Descriptive statistics, Wilcoxon rank-sum, Pearsons chi-square and Fishers exact test were used. RESULTS 43 cases met inclusion criteria. AL was characterized by method of diagnosis as follows: change in drain output only (DO, n=8); change in drain output associated with ambiguous clinical signs/symptoms (D-SSX, n=11); or clinical signs/symptoms only (SSX, n=24). The sensitivity of drains in diagnosing AL was 50%. Time to diagnosis was earlier in DO/D-SSX (median 7 vs. 11 days, P=0.003), however, no significant differences were observed in rates of reoperation, length of stay, time to chemotherapy (TTC), and 30- and 90-day mortality between DO/D-SSX and SSX. Comparing cases where no drains were placed (n=5) vs. those with drain (n=38), we observed no differences in outcomes. TTC though statistically significant (47 vs. 59 days, P=0.023) was not clinically significant. CONCLUSIONS Though a change in drain output correlated with earlier diagnosis, this did not appear to impact overall outcomes. We did not find strong evidence supporting routine prolonged drainage after LBR for OC. Additionally, absence of change in drain output does not rule out presence of AL.