Morphofunctional changes in the placenta after ozone therapy

Macro- and microscopic aspects in the morphology of placenta after ozone therapy were studied in pregnant women with placental insufficiency and the results were compared with the control group. In the main group, the placentas were smaller and weighed less. After ozone therapy enlargement of terminal villi with true syncytiocapillary membranes was noted. A stimulating effect of ozone therapy on the growth and differentiation of terminal villi was established. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 7, pp. 117–120, July, 2000     

Enhanced Recovery after Surgery (ERAS) in Gynecologic Surgery—A Review

Purpose of Review

The purpose of this review is to summarize the newly published guidelines on enhanced recovery after surgery (ERAS) in gynecologic oncology and discuss recent studies evaluating the outcomes of ERAS implementation in general gynecology and gynecologic oncology.

Recent Findings

ERAS guidelines for gynecologic surgery include preoperative diet, preoperative education, multimodal analgesia, early postoperative feeding, early mobilization and urinary catheter removal, avoidance of mechanical bowel preparation and drains, maintenance of normothermia, and minimal fluid shifts. The studies evaluated in this update include mostly retrospective observational studies and few randomized controlled trials. The primary outcome of the majority of studies, length of stay, was found to be less after ERAS implementation than prior to implementation. Secondary outcomes such as rates of readmission, mortality, and postoperative complications yielded mixed results; however, most differences were not statistically significant. Hospital costs also decreased after ERAS implementation, but the cost differences were only statistically significant in half of the studies with a single dissenting study.

Summary

Implementation of ERAS protocols in gynecologic surgery is becoming ubiquitous as more evidence demonstrates improved patient outcomes and decreased healthcare costs. However, the majority of studies evaluating the efficacy of ERAS protocols are retrospective studies. Now that a standardized set of enhanced recovery guidelines in gynecologic oncology have been published, more institutions will hopefully begin to implement ERAS programs. Future research should subsequently include prospective, randomized controlled trials to validate the benefits concluded from studies based on historical data.

     

Extended pelvic resections for recurrent or persistent uterine and cervical malignancies: an update on out of the box surgery

Objective

To update our report on the outcome of patients who underwent extended pelvic resection (EPR) for recurrent or persistent uterine and cervical malignancies.

Methods

We reviewed the records of all patients who underwent EPR between 6/2000 and 07/2011. EPR was defined as an en-bloc resection of a pelvic tumor with sidewall muscle, bone, major nerve, and/or major vascular structure. Complications up to 180 days post surgery were analyzed. Survivals were estimated using the Kaplan-Meier method.

Results

We identified 22 patients. Median age at the time of EPR was 58 years (range, 36-74). Median tumor diameter was 5.4 cm (range, 1.5-11.2). Primary tumor sites included: uterus, 13; cervix, 7; synchronous uterus/cervix, 1; and synchronous uterus/ovary, 1. The EPR structures were: muscle, 13; nerve, 10; bone, 8; vessel, 5. Complete gross resection with microscopically negative margins (R0 resection) was achieved in 17 patients (77%). There were no perioperative mortalities. Major postoperative complications occurred in 14 patients (64%). The two most common morbidities were pelvic abscesses and peripheral neuropathies. Median follow-up time was 28 months (range, 6-99). The 5-year overall survival (OS) for the entire cohort was 34% (95% CI, 13-57). For the 17 patients who had an R0 resection, the 5-year OS was 48% (95% CI, 19-73). In patients with positive pathologic margins (n = 5), the 5-year OS was 0%.

Conclusion

EPR was associated with prolonged survival when an R0 resection was achieved. The high rate of postoperative complications remains a hallmark of these procedures and properly selected patients should be extensively counseled preoperatively.     

Anti-IL-16 therapy reduces CD4+ T-cell infiltration and improves paralysis and histopathology of relapsing EAE

Infiltration of the central nervous system (CNS) by CD4+ Th1 cells precedes onset and relapses of experimental autoimmune encephalomyelitis (EAE). We reported that (B6xSJL) F1 (H-2b/s) mice with severe relapsing-remitting disease had extensive infiltration by CD4+ T cells compared to that in C57BL/6 (B6) (H-2b) mice, which developed mild low-relapsing disease in response to myelin oligodendrocyte peptide 35-55 (MOG(35-55)). This observation led us to search for mechanisms that specifically regulate trafficking of CD4+ cells in relapsing H-2b/s mice. We show that the CD4+ cell chemoattractant cytokine interleukin (IL)-16 has an important role in regulation of relapsing EAE induced by MOG(35-55) in the (B6xSJL) F1 (H-2b/s) mice. We found production of IL-16 in the CNS of mice with EAE. IL-16 levels in the CNS correlated well with the extent of CD4+ T-cell and B-cell infiltration during acute and relapsing disease. Infiltrating CD4+ T cells, B cells, and to a lesser extent CD8+ T cells all contained IL-16 immunoreactivity. Treatment with neutralizing anti-IL-16 antibody successfully reversed paralysis and ameliorated relapsing disease. In treated mice, diminished infiltration by CD4+ T cells, less demyelination, and more sparing of axons was observed. Taken together, our results show an important role for IL-16 in regulation of relapsing EAE. We describe a novel therapeutic approach to specifically impede CD4+ T cell chemoattraction in EAE based on IL-16 neutralization. Our findings have high relevance for the development of new therapies for relapsing EAE and potentially MS.     

Age‐Stratified Risk of Unexpected Uterine Sarcoma Following Surgery for Presumed Benign Leiomyoma

Background.

Estimates of unexpected uterine sarcoma following surgery for presumed benign leiomyoma that use age-stratification are lacking.

Patients and Methods.

A retrospective cohort of 2,075 patients that had undergone myomectomy was evaluated to determine the case incidence of unexpected uterine sarcoma. An aggregate risk estimate was generated using a meta-analysis of similar studies plus our data. Database-derived age distributions of the incidence rates of uterine sarcoma and uterine leiomyoma surgery were used to stratify risk by age.

Results.

Of 2,075 patients in our retrospective cohort, 6 were diagnosed with uterine sarcoma. Our meta-analysis revealed 8 studies from 1980 to 2014. Combined with our study, 18 cases of leiomyosarcoma are reported in 10,120 patients, for an aggregate risk of 1.78 per 1,000 (95% confidence interval [CI]: 1.1–2.8) or 1 in 562. Eight cases of other uterine sarcomas were reported in 6,889 patients, for an aggregate risk of 1.16 per 1,000 (95% CI: 0.5–4.9) or 1 in 861. The summation of these risks gives an overall risk of uterine sarcoma of 2.94 per 1,000 (95% CI: 1.8–4.1) or 1 in 340. After stratification by age, we predict the risk of uterine sarcoma to range from a peak of 10.1 cases per 1,000, or 1 in 98, for patients aged 75–79 years to <1 case per 500 for patients aged <30 years.

Conclusion.

The risk of unexpected uterine sarcoma varies significantly across age groups. Our age-stratified predictive model should be incorporated to more accurately counsel patients and to assist in providing guidelines for the surgical technique for leiomyoma.     

Role of preoperative MR imaging in the evaluation of patients with persistent or recurrent gynaecological malignancies before pelvic exenteration

Purpose

To determine the diagnostic performance of MRI in assessing local tumour extent and evaluate associations between MRI features and survival in patients undergoing MRI before pelvic exenteration for persistent or recurrent gynaecological cancers.

Methods and materials

The study included 50 patients with persistent or recurrent gynaecological malignancies who underwent pelvic exenteration between January 1999 and December 2011 and had MRI at most 90 days before surgery. Two radiologists independently assessed invasion of adjacent organs (on a 5-point scale). Diagnostic accuracy, inter-reader agreement, and associations between organ invasion on MRI and patient survival were evaluated.

Results

Areas under receiver operating characteristic curves (AUCs) for invasion of the bladder, rectum and pelvic sidewall were 0.96, 0.90 and 0.98 for reader 1 and 0.95, 0.88 and 0.90 for reader 2. Corresponding sensitivities/specificities were 87.0 %/92.6 %, 81.3 %/97.0 % and 87.5 %/97.2 % for reader 1, and 87.0 %/100.0 %, 75.0 %/97.0 % and 75.0 %/94.4 % for reader 2. Inter-reader agreement was excellent for organ invasion (κ?=?0.81–0.85). Pelvic sidewall invasion on MRI was associated with overall and recurrence-free survival (P?=?0.01–0.04 for the two readers).

Conclusion

Preoperative MRI is accurate in predicting organ invasion. It may guide surgical planning and serve as a predictive biomarker in patients undergoing pelvic exenteration for gynaecological malignancies.

Key Points

? MRI can accurately assess bladder and rectal wall invasion before major surgery. ? MRI identifies patients requiring extended pelvic exenteration by detecting sidewall invasion. ? Inter-reader agreement for detecting organ invasion and tumor size is excellent. ? Pelvic sidewall invasion on MRI is associated with shorter overall and recurrence-free survival.     

Anterior pelvic exenteration with total vaginectomy for recurrent or persistent genitourinary malignancies: review of surgical technique, complications, and outcome

Objective

To describe the surgical technique, complications, and outcomes after anterior pelvic exenteration with total vaginectomy (AETV) for recurrent or persistent genitourinary malignancies.

Methods

We reviewed the medical records of all patients who underwent AETV between 12/2002 and 07/2011. Relevant demographic, clinical, and pathological information was collected. Postoperative complications and rates of readmission and reoperation (up to 180 days after surgery) were examined, and preliminary survival data were obtained.

Results

We identified 11 patients who underwent AETV. The median age at the time of the surgery was 55 years (range, 36-71). The median tumor size was 0.9 cm (range, microscopic — 4). Primary tumor sites included: cervix, 6; uterus, 3; vagina, 1; and urethra, 1. Complete surgical resection with negative pathologic margins was achieved in all 11 patients. Major postoperative complications occurred in 4 patients (36%). Six patients (55%) required readmission to the hospital. No operative mortalities were observed, and none of the patients required a re-operation. With a median follow-up after the procedure of 25 months (range, 6-95), none of the patients developed a pelvic recurrence. Ten patients (91%) were alive without evidence of disease and one patient (9%) developed a pancreatic recurrence.

Conclusion

AETV sparing the rectosigmoid and anus is feasible in highly selected patients with central pelvic recurrences. Compared to previously reported studies on total pelvic exenteration, data from this case series suggest that AETV may be associated with a lower rate of complications without compromising the oncologic outcome, while also preserving rectal function.     

Randomised phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer

Background This multi-center RP2 study assessed activity/safety of ixabepilone + bevacizumab compared to ixabepilone in platinum-resistant/refractory ovarian/fallopian tube/primary peritoneal cancer. Additional objectives were to examine the role of prior bevacizumab and taxanes, and explore class III-ß-tubulin (TUBB3) as a predictive biomarker.Methods Participants were randomised to receive ixabepilone 20 mg/m² days 1, 8, 15 with (IXA + BEV) or without (IXA) bevacizumab 10 mg/kg days 1, 15 every 28 days. Patients were stratified by prior BEV. The primary endpoint was PFS. OS, safety, and ORR served as secondary endpoints.Results Among 76 evaluable patients who received IXA + BEV (n = 39) compared to IXA (n = 37), the ORR was 33% (n = 13) versus 8% (n = 3)(P = 0.004), durable at 6 months in 37% (n = 14) and 3% (n = 1) (P < 0.001). BEV significantly improved PFS (median:5.5 vs 2.2 months, HR = 0.33, 95%CI 0.19–0.55, P < 0.001) and OS (median:10.0 vs 6.0 months, HR = 0.52, 95%CI 0.31–0.87, P = 0.006). Both regimens were well-tolerated. TUBB3 expression did not predict response. Subgroup analyses revealed minimal effect of prior BEV or taxane resistant/refractory status on response to IXA + BEV.Conclusions IXA + BEV is a well-tolerated, effective combination for platinum/taxane-resistant ovarian cancer that extends PFS and likely OS relative to IXA monotherapy. Prior receipt of BEV should not preclude the use of IXA + BEV. TUBB3 is not a predictive biomarker.Clinical trial registration NCT3093155.Subject terms: Translational research, Phase II trials