Intra-obturator bupivacaine injection and post-operative pain following the trans-obturator tension-free vaginal tape procedure: randomized study.

PURPOSE: To assess the effectiveness of a long-acting anesthetic injection into the obturator membrane for pain relief in women undergoing trans-obturator tension-free vaginal tape. METHODS: A total of 22 women were randomized for the intra-operative injection of bupivacaine into one of their obturator membranes: the left or right side. All the participants were asked to define their groin pain on a visual analog scale (scored 0-10 cm) at 1, 6, 12, and 24 h post-operative. For each woman, pain scores were compared between the local anesthetic-injected side and the opposite side. RESULTS: Statistically significant differences were not observed in groin pain scores between the bupivacaine injection side and the no injection side at 1 h (p = 0.76), 6 h (p = 1), 12 h (p = 0.95), and 24 h (p = 0.82) post-operative. CONCLUSION: In women who undergo trans-obturator tension-free vaginal tape procedures, intra-operative intra-obturator injection of local anesthetics is not effective in alleviating the characteristic post-operative groin pain. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov (NCT03479996).

Anatomical and functional outcomes of uterus preservation and pelvic organ prolapse repair with vaginal trocar-less mesh kit (Endofast): A retrospective study of 239 patients.

OBJECTIVE: The aim of the study was to assess safety and long term efficacy as well as short and long term complications of vaginal prolapse mesh repair using single incision trocar-less system while preserving the uterus. STUDY DESIGN: A single-center, retrospective cohort study including all patients who underwent vaginal prolapse mesh repaier surgery with EndoFast Reliant™ kit between October 2010 and January 2015. Outcomes included anatomical changes (POP-Q), overactive bladder symptoms (OAB) stress urinary incontinence (SUI), sexual function and constipation as well as the rate of surgical failure, immediate and long-term complications. RESULTS: 239 women, with an average follow-up period of 1.7 years (range: 6 weeks to 7 years), were included. Uterus was preserved in 87 % of patients (184 out of 211 patients with intact uterus) and concurrent surgery for SUI was performed in 46 %. POP-Q significantly improved as well as OAB and SUI symptoms and remained without significant change during follow-up period. In 11 patients (4.6 %) a new/recurrent prolapse was observed during the follow up period. Immediate complications occurred in 4 patients. One case of bladder perforation, one case of mesh contamination, 2 cases of urinary retention, one of them permanent. Late complications included mesh erosion, de novo dyspareunia, cervical elongation and de-novo SUI, and were observed in 38 cases (16 %). Surgical intervention was required in 20 (8.4 %) cases; 10 cases of de-novo SUI, 2 cases of partial mesh removal because of dyspareunia, 1 case of mid urethral sling removal because of erosion and 7 cases of cervical amputation. CONCLUSIONS: Repair of prolapse with vaginal trocar-less mesh kit while preserving the uterus for the majoroty of women, is a relatively safe and effective surgery,with a low incidence of complications and re-operation rate which was mainly for de novo SUI or elongation of cervix. Randomiesed prospective long term studies are neaded to establish the results.

[Umbilical cord cyst--should it concern us?].

INTRODUCTION: Advancements in sonographic technology have led to improved prenatal detection of fetal umbilical cord and placental anomalies. The prevalence of umbilical cord cystic masses detected in the first trimester is 0.4% to 3.4%. The second- and third-trimester umbilical cord cysts are a rare sonographic finding and its prevalence is unknown. There is a strong association between umbilical cord cysts and fetal anomalies but not in all cases. The main questions are: what are the implications of these findings and what is the prenatal follow-up that should be offered. CASE REPORT: In this study the authors present a case in which an umbilical cord cyst was diagnosed at 29 weeks of gestation following normal integrated test and anatomical sonographic survey. At 32 weeks of gestation, fetal karyotype was found to be normal. The outcome of the pregnancy was normal and so was the developmental follow-up during the first three years. DISCUSSION AND CONCLUSIONS: From the literature survey it appears that transient first-trimester cysts are not associated with chromosomal anomaLies, yet they might be associated with congenital maLformations, especially those of the abdominal wall and the urinary tract, and should lead to further detailed sonographic evaluation. Routine karyotype may not be necessary. Second and third trimester umbilical cord cystic masses accompanied by additional malformations are strongly associated with chromosomal anomalies, especially with trisomy 18. Second- and third-trimester umbilical cord cystic masses without additional abnormal findings were also found to be associated with chromosomal anomalies in some works. Therefore, these findings should be an indication for fetal karyotype. In the case of an isolated umbilical cord cyst with normal karyotype, serial sonographic evaluation is needed. If all these are normal, it may be presumed that the cyst is an isolated umbilical cord anomaly and that the fetal prognosis is good.

DeltaNp63alpha levels correlate with clinical tumor response to cisplatin.

After exposure to damaging agents, the p53 tumor suppressor is stabilized mediating cell cycle arrest and apoptosis. p53 family member, DeltaNp63 promotes cell proliferation and accelerates tumor growth. We previously found that the genotoxic stress agents induced a decrease of DeltaNp63alpha. We further observed that genotoxic stress mediated phosphorylation of DeltaNp63alpha targeting it into proteasome degradation. Here, we found that high DeltaNp63 protein levels in primary tumors accurately predicted response to platinum based chemotherapy and a favorable outcome in head and neck cancer patients. Our data suggest that degradation of DeltaNp63alpha is part of the cellular response to DNA damage in head and neck cancers. The findings may have implications for the rational use of DNA damaging agents in human cancer.

RACK1 and stratifin target DeltaNp63alpha for a proteasome degradation in head and neck squamous cell carcinoma cells upon DNA damage.

p53 family members with a transactivation (TA) domain induce cell cycle arrest and promote apoptosis. However, DeltaNp63 isotypes lacking the TA-domain promote cell proliferation and tumorigenesis in vitro and in vgammavo. Although p53, TAp63 or TAp73 are stabilized upon DNA damage, we found that the genotoxic stress agents induced a dramatic decrease and phosphorylation of DeltaNp63alpha in squamous cell carcinoma cells. Further work revealed that RACK1 physically associated with the p63alpha C-terminal domain through its WD40 domain. However, stratifin binds with phosphorylated DeltaNp63alpha in response to cisplatin. Upon DNA damage induced by cisplatin, stratifin mediated a nuclear export of DeltaNp63alpha into cytoplasm and then RACK1 targeted latter into a proteasome degradation pathway possibly serving as an E3 ubiquitin ligase. Moreover, siRNA knockdown of both stratifin and RACK1 inhibited a nuclear export and protein degradation of DeltaNp63alpha, respectively. Our data suggest that modification and down regulation of DeltaNp63alpha is one of the major determinants of the cellular response to DNA damage in human head and neck cancers.

Molecular analysis of peritoneal fluid in ovarian cancer patients.

To determine whether genetic abnormalities present in primary ovarian tumors can be used to detect cancer cells in peritoneal fluid, we tested 14 ovarian cancers and 1 benign tumor of the ovary for loss of heterozygosity (LOH) at chromosomal arms 13q, 17p, 17q, and 22q and for mutations in the p53 and K-ras genes. In each case, matched primary tumor, normal tissue, and peritoneal fluid were analyzed. The highest frequency of LOH was found on chromosomal arm 17p (42%), followed by chromosomal arm 17q (36%), 22q (30%), and 13q (21%). Identical alterations were detected in matched peritoneal fluid (either peritoneal wash or ascitic fluid) in 3 of the 8 patients with LOH in the tumor (38%). Direct sequence analysis detected p53 mutations in 3 of the 14 malignant tumors (21%) and no (0) K-ras mutations. Identical mutations were detected in matched peritoneal fluid from all 3 patients with p53 mutations. All 8 of the 14 (57%) malignant tumors that showed at least one genetic abnormality were serous adenocarcinoma and identical alterations were detected in 5 of the 8 (62%) matched peritoneal fluid samples. Our findings indicate that molecular abnormalities can be detected in peritoneal fluid from patients with ovarian cancer and may be used to complement current conventional diagnostic procedures for detection of primary ovarian cancer.

DeltaNp63 induces beta-catenin nuclear accumulation and signaling.

The P53 homolog p63 encodes multiple proteins with transactivating, apoptosis-inducing, and oncogenic activities. We showed that p63 is amplified and that DeltaNp63 isotypes are overexpressed in squamous cell carcinoma (SCC) and enhance oncogenic growth in vitro and in vivo. Moreover, p53 associated with DeltaNp63alpha and mediated its degradation. Here, we report that DeltaNp63 associates with the B56alpha regulatory subunit of protein phosphatase 2A (PP2A) and glycogen synthase kinase 3beta (GSK3beta), leading to a dramatic inhibition of PP2A-mediated GSK3beta reactivation. The inhibitory effect of DeltaNp63 on GSK3beta mediates a decrease in phosphorylation levels of beta-catenin, which induces intranuclear accumulation of beta-catenin and activates beta-catenin-dependent transcription. Our results suggest that DeltaNp63 isotypes act as positive regulators of the beta-catenin signaling pathway, providing a basis for their oncogenic properties.