The EnPlace® sacrospinous ligament fixation-A novel minimally invasive transvaginal procedure for apical pelvic organ prolapse repair: Safety and short-term outcome results.

OBJECTIVE: The EnPlace® device is a novel minimally invasive tool allowing transvaginal sacrospinous ligament (SSL) fixation of apical pelvic organ prolapse (POP). The study aimed to investigate the safety and short-term efficacy of the EnPlace® SSL fixation for significant apical POP repair. METHODS: A retrospective cohort study of 123 consecutive patients (mean age 64.4 ± 11.1 years) with stage III or IV apical POP who underwent SSL fixation by the EnPlace® device. Safety and 6-month outcome results were analyzed and compared between 91 (74%) patients with uterine prolapse versus 32 (26%) patients with vaginal vault prolapse. RESULTS: There were no intraoperative or early postoperative complications. The mean (± standard deviation) duration of surgery was 30 ± 6.9 min and mean blood loss was 30.5 ± 18.5 mL. The average position of point C by POP-Quantification measurements before surgery and at 6 months postoperatively was 4.5 ± 2.8 cm and -3.1 ± 3.3 cm, respectively. Of 91 patients with preoperative uterine prolapse, eight (8.8%) patients developed a recurrent uterine prolapse within 6 months postoperatively. Of 32 patients with preoperative vault prolapse, two patients (6.3%) had recurrent vault prolapse. CONCLUSION: Short-term outcome results of EnPlace® SSL fixation suggest that it is a safe and effective minimally invasive transvaginal procedure for significant apical POP repair.

The Manchester operation - is it time for it to return to our surgical armamentarium in the twenty-first century?

We conducted a study to assess the efficacy and outcome results of Manchester operation for women with symptomatic elongation of uterine cervix between 2010 and 2020. Forty-five women were enrolled. Mean age was 54.2 ± 10.5 years, 57.5% were premenopausal. Mean follow up was 4.53 years. Most patients were pleased from the surgery: 29 (76.3%) very pleased and three (7.9%) quite pleased. There were four cases of late postoperative complications: hematometra, pyometra, vesicovaginal fistula and small bowel evisceration through the posterior vaginal fornix. All four cases required surgical interventions with complete recovery. Manchester operation is an effective procedure for symptomatic elongation of uterine cervix. The surgery is short, minimal blood loss and without significant intraoperative complications. However, it is not free of late postoperative complications and it is therefore important that the surgery will be carried out with a strict technique and by skilled surgeons who are capable to manage unique postoperative complications.Impact StatementWhat is already known on this subject? Elongation of the uterine cervix is a condition that has not been sufficiently studied. Up-to-date data regarding the efficacy and safety of the Manchester operation for patients with cervical elongation and normal pelvic support are scarce, as most previously published studies included mainly patients with uterine prolapse.What do the results of this study add? The present study presents the efficacy, complications and clinical outcomes of Manchester operation for women with elongation of the uterine cervix. Our results show that Manchester operation is safe, effective method for symptomatic uterine cervix elongation.What are the implications of these findings for clinical practice and/or further research? This suggests Manchester operation is an effective procedure for symptomatic uterine cervix elongation should be implemented more widely. It must be carried out with a strict technique by skilled surgeons capable to manage unique postoperative complications.

A tailored flexible vaginal pessary treatment for pelvic organ prolapse in older women.

OBJECTIVES: To present a flexible protocol of vaginal pessaries for older women with significant pelvic organ prolapse (POP). DESIGN: A prospective cohort study of 140 consecutive older women (aged ≥65 years) with significant POP treated with individually fitted vaginal pessaries. After initial insertion, each patient was invited for a first evaluation after 1 month and subsequent follow-ups at increasing intervals of 1 month. During each examination, the pessary was removed and the vagina was inspected for infection, bleeding, or erosions. All patients were advised to use a vaginal estrogen cream twice a week. SETTING: The study was conducted during 2020 in the urogynecology clinic of a tertiary medical center. PARTICIPANTS: The study cohort included 140 consecutive older women with significant and symptomatic POP treated with vaginal pessaries. MAIN OUTCOME: Primary outcomes included time intervals between follow-up visits, pessary-associated complications, need to change the pessary, need to remove the pessary temporarily, and whether the patients eventually underwent POP surgery. RESULTS: The mean age of the patients at the time of pessary fitting was 76.7 ± 9.2 years (range 65-100 years). Mean interval between follow-up examinations was 3.3 ± 1.1 months (range 1-6 months). Most patients (83.6%) used a ring pessary with support, but only a small number of patients were able to maintain the pessary by themselves. Of the 140 patients, five (3.6%) patients only eventually underwent POP surgery, and in 11 (7.9%) patients, the vaginal pessary had to be removed for 2-4 weeks because of significant vaginal discharge or superficial erosions. Additionally, 12 (8.6%) patients developed stress urinary incontinence following pessary insertion. CONCLUSIONS: Customized management with vaginal pessary for symptomatic POP in older women is effective and safe, and is a suitable therapeutic alternative for older women who are unable or unwilling to undergo reconstructive pelvic surgery.

Stromal invasion pattern identifies patients at lowest risk of lymph node metastasis in HPV-associated endocervical adenocarcinomas, but is irrelevant in adenocarcinomas unassociated with HPV.

OBJECTIVE: The Silva invasion pattern-based classification system stratifies endocervical adenocarcinomas (ECAs) into 3 categories corresponding to risk of metastasis and recurrence, but has only been evaluated for HPV-associated ECAs of usual type. We examined whether the Silva system is applicable to all endocervical adenocarcinomas, especially those not associated with HPV. METHODS: Complete slide sets from 341 surgical specimens of ECA were collected from 7 institutions worldwide. All specimens were associated with clinical records covering at least 5 years of follow-up. Tumors were classified as HPV-associated (HPVA) or not (NHPVA) by both morphology and detection of HPV using in situ hybridization. Recurrence and survival were analyzed by multivariate Mantel-Haenszel methods. RESULTS: Most specimens (292; 85.6%) were HPVA, while 49 (14.3%) were NHPVA. All NHPVAs were Silva pattern C, while 76.0% of HPVAs were pattern C, 14.7% pattern A, and 9.3% pattern B. Including both HPVAs and NHPVAs, lymphovascular invasion (LVI) was detected in 0% of pattern A, 18.5% of pattern B and 62.6% of pattern C cases (p < 0.001). None of the pattern A or B cases were associated with lymph node metastases (LNM), in contrast to pattern C cases (21.8%). Among patients with Silva pattern C ECA, those with HPVA tumors had a lower recurrence rate and better survival than those with NHPVA; however, when adjusted for stage at diagnosis, the difference in recurrence and mortality was small and not statistically significant. CONCLUSIONS: Application of the Silva system is only relevant in HPVA cervical adenocarcinoma.

Localization of luteinizing hormone receptor protein in the human ovary.

The luteinizing hormone receptor (LHR) plays a pivotal role during follicular development. Consequently, its expression pattern is of major importance for research and has clinical implications. Despite the accumulated information regarding LHR expression patterns, our understanding of its expression in the human ovary, specifically at the protein level, is incomplete. Therefore, our aim was to determine the LHR protein localization and expression pattern in the human ovary. We examined the presence of LHR by immunohistochemical staining of human ovaries and western blots of mural granulosa and cumulus cells aspirated during IVF treatments. We were not able to detect LHR protein staining in primordial or primary follicles. We observed equivocal positive staining in granulosa cells and theca cells of secondary follicles. The first appearance of a clear signal of LHR protein was observed in granulosa cells and theca cells of small antral follicles, and there was evidence of increasing LHR production as the follicles mature to the pre-ovulatory stage. After ovulation, LHR protein was ubiquitously produced in the corpus luteum. To confirm the expression pattern in granulosa cells and cumulus cells, we performed western blots and found that LHR expression was stronger in granulosa cells than in cumulus cells, with the later demonstrating low, but still significant, amounts of LHR protein. In summary, we conclude that LHR protein starts to appear on granulosa cells and theca cells of early antral follicles, and low but significant expression of LHR exists also in the cumulus cells. These results may have implications for the future design of clinical protocols and culture mediums for in vitro fertilization and especially in vitro maturation of oocytes.

Bragg spectroscopy of a strongly interacting 85Rb Bose-Einstein condensate.

We report on measurements of the excitation spectrum of a strongly interacting Bose-Einstein condensate. A magnetic-field Feshbach resonance is used to tune atom-atom interactions in the condensate and to reach a regime where quantum depletion and beyond mean-field corrections to the condensate chemical potential are significant. We use two-photon Bragg spectroscopy to probe the condensate excitation spectrum; our results demonstrate the onset of beyond mean-field effects in a gaseous Bose-Einstein condensate.

Bladder perforation during tension-free vaginal tape surgery: does it matter?

OBJECTIVE: To analyze the incidence, possible risk factors, preoperative morbidity and outcome results in tension-free vaginal tape (TVT) cases complicated by lower urinary tract injury in a large, heterogeneous, consecutive group of women. STUDY DESIGN: Four hundred sixty consecutive women who underwent TVT surgery for correction of urodynamically proven stress urinary incontinence were enrolled prospectively. All the procedures were performed at 1 center by 3 experienced surgeons. RESULTS: In this series, 3.9% cases of lower urinary tract injury occurred. Most of the injuries occurred during the learning curve. TVT-related urinary tract injury was not associated with increased perioperative morbidity. The cure rates were similar with and without injury. De novo urge and persistent urge incontinence were slightly more common in patients with bladder perforation. CONCLUSION: Lower urinary tract injury during the TVT procedure is directly related to the inexperience of the surgeon. However, TVT-related lower urinary tract injury does not appear to affect medium-term outcome results.

Scattering length instability in dipolar Bose-Einstein condensates.

We predict a new kind of instability in a Bose-Einstein condensate composed of dipolar particles. Namely, a comparatively weak dipole moment can produce a large, negative two-body scattering length that can collapse the Bose-Einstein condensate. To verify this effect, we validate mean-field solutions to this problem using exact, diffusion Monte Carlo methods. We show that the diffusion Monte Carlo energies are reproduced accurately within a mean-field framework if the variation of the s-wave scattering length with the dipole strength is accounted for properly.

A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas.

Standard cytotoxic treatments for neuroendocrine tumours have been associated with limited activity and remarkable toxicity. A phase II study was designed to evaluate the efficacy, safety and pharmacodynamics of temsirolimus in patients with advanced neuroendocrine carcinoma (NEC). Thirty-seven patients with advanced progressive NEC received intravenous weekly doses of 25 mg of temsirolimus. Patients were evaluated for tumour response, time to progression (TTP), overall survival (OS) and adverse events (AE). Twenty-two archival specimens, as well as 13 paired tumour biopsies obtained pretreatment and after 2 weeks of temsirolimus were assessed for potential predictive and correlative markers. The intent-to-treat response rate was 5.6% (95% CI 0.6-18.7%), median TTP 6 months and 1-year OS rate 71.5%. The most frequent drug-related AE of all grades as percentage of patients were: fatigue (78%), hyperglycaemia (69%) and rash/desquamation (64%). Temsirolimus effectively inhibited the phosphorylation of S6 (P=0.02). Higher baseline levels of pmTOR (phosphorylated mammalian target of rapamycin) (P=0.01) predicted for a better response. Increases in pAKT (P=0.041) and decreases in pmTOR (P=0.048) after treatment were associated with an increased TTP. Temsirolimus appears to have little activity and does not warrant further single-agent evaluation in advanced NEC. Pharmacodynamic analysis revealed effective mTOR pathway downregulation.

[Post partum anal incontinence].

Vaginal delivery is one of the main causes of anal incontinence. While previously postpartum anal incontinence was attributed to neurological damage to the pelvic floor and the rectal sphincter, today we know that mechanical injury plays an important role, especially when symptoms start soon after delivery. Risk factors for postpartum fecal incontinence are: forceps delivery, nulliparity, birth weight over 4 kilograms and persistent occiput posterior presentation of the fetal head. Anal incontinence developed in 42% of women who had posterolateral episiotomy. Therefore, the main focus of the treating physician should be on prevention by avoiding birth trauma followed by early recognition and skilful correction.

Can the eigenstates of a many-body Hamiltonian be represented exactly using a general two-body cluster expansion?

It is proved that a recent conjecture that the exact ground-state wave function of an arbitrary many-fermion system with one- and two-body interactions may be represented by an exponential cluster expansion employing finite two-body operators, starting from any reference function sufficiently close to the exact eigenfunction, is not valid. We show that the space of initial reference functions which lead to the exact ground state is of dimension equal to the number of two-body operators. If the dimension of the multiparticle space is greater than the number of two-body operators, then the space of good reference functions is of measure zero in it.

Accelerated usual interstitial pneumonitis, anti-DNA antibodies and hypocomplementemia.

A healthy 60-year-old patient presented with progressive dyspnoea. Clinical, radiographic and pathological features of interstitial lung disease were found and an open lung biopsy established the diagnosis of usual interstitial pneumonitis (UIP) (idiopathic pulmonary fibrosis). Despite treatment, the patient died 4 months later in respiratory failure. Although the patient had no extra-thoracic involvement at autopsy, his illness was associated with a very high titre of anti-double-stranded DNA antibodies, hypocomplementemia, hypergammaglobulinaemia and lymphoid hyperplasia. These features and a literature review, suggest immune-mediated lung damage in a subset of patients with UIP.

Apoptosis is associated with triacylglycerol accumulation in Jurkat T-cells.

Magnetic resonance spectroscopy is increasingly used as a non-invasive method to investigate apoptosis. Apoptosis was induced in Jurkat T-cells by Fas mAb. (1)H magnetic resonance spectra of live cells showed an increase in methylene signal as well as methylene/methyl ratio of fatty acid side chains at 5 and 24 h following induction of apoptosis. To explain this observation, (1)H magnetic resonance spectra of cell extracts were investigated. These demonstrated a 70.0+/-7.0%, 114.0+/-8.0% and 90.0+/-5.0% increase in the concentration of triacylglycerols following 3, 5 and 7 h of Fas mAb treatment (P<0.05). Confocal microscopy images of cells stained with the lipophilic dye Nile Red demonstrated the presence of lipid droplets in the cell cytoplasm. Quantification of the stained lipids by flow cytometry showed a good correlation with the magnetic resonance results (P > or =0.05 at 3, 5 and 7 h). (31)P magnetic resonance spectra showed a drop in phosphatidylcholine content of apoptosing cells, indicating that alteration in phosphatidylcholine metabolism could be the source of triacylglycerol accumulation during apoptosis. In summary, apoptosis is associated with an early accumulation of mobile triacylglycerols mostly in the form of cytoplasmic lipid droplets. This is reflected in an increase in the methylene/methyl ratio which could be detected by magnetic resonance spectroscopy.

[Nephrogenic adenoma--benign lesion of urinary tract system].

Nephrogenic adenoma is a rare metaplastic benign lesion of the urinary tract caused by chronic irritation to the urinary epithelium. The appearance of this lesion is usually characterized by hematuria and irritative symptoms. Nephrogenic adenoma may be found most commonly in the bladder and the urethra and less frequently in the renal pelvis and ureters. We present 5 patients who underwent surgery due to bladder or urethral nephrogenic adenoma. Despite the fact that nephrogenic adenoma is a benign lesion, long term follow-up is needed due to the high recurrence rate and the potential, though rare, malignant transformation.

Imaging biochemistry: applications to breast cancer.

The use of magnetic resonance spectroscopy (MRS) to investigate breast tumour biochemistry in vivo is reviewed. To this end, results obtained both from patients in vivo and from tumour extracts and model systems are discussed. An association has been observed between transformation and an increase in phosphomonoesters (PMEs) detected in the 31P MRS spectrum, as well as an increase in choline-containing metabolites detected in the 1H spectrum. A decrease in PME content after treatment is associated with response to treatment as assessed by tumour volume. Experiments in model systems aimed at understanding the underlying biochemical processes are presented, as well as data indicating the usefulness of MRS in monitoring the uptake and metabolism of some chemotherapeutic agents.

Magnetic resonance detects changes in phosphocholine associated with Ras activation and inhibition in NIH 3T3 cells.

Ras is frequently mutated in cancer, and novel therapies are being developed to target Ras signalling. To identify non-invasive surrogate markers of Ras activation and inhibition, we used(31)P magnetic resonance spectroscopy (MRS) and investigated NIH 3T3 cells compared to a mutant ras transfected counterpart. The MR spectra indicated that phosphocholine (PC) levels increased significantly from 3 +/- 2 fmol cell(-1)in NIH 3T3 cells to 13 +/- 4 fmol cell(-1)in the transfected cells. The PC/NTP ratio increased significantly from 0.3 +/- 0.1 to 0.7 +/- 0.3. This could not be explained by either a faster proliferation rate or by alterations in cell cycle distribution. Both cell lines were treated with simvastatin, 17-AAG and R115777, agents which inhibit Ras signalling. Cell proliferation was inhibited in both cell lines. The spectrum of NIH 3T3 cells was not affected by treatment. In contrast, in the ras transfected cells growth inhibition was associated with an average 35 +/- 5% drop in PC levels and a comparable drop in PC/NTP. Thus the MRS visible increase in phosphocholine is associated with Ras activation, and response to treatment is associated with partial reversal of phosphocholine increase in ras transfected cells. MRS might therefore be a useful tool in detecting Ras activation and its inhibition following targeted therapies.

Treatment of SW620 cells with Tomudex and oxaliplatin induces changes in 2-deoxy-D-glucose incorporation associated with modifications in glucose transport.

UNLABELLED: Many studies suggest that changes in the uptake of the glucose analog FDG after therapy, compared with pretreatment uptake, predicts tumor response to therapy. However, clinical interpretation is compromised by a limited understanding of the effect of therapy on FDG and 2-deoxy-D-glucose (DG) uptake at the tumor cell level. METHODS: Uptake of 2-deoxy-D-[1-(3)H]glucose (3H-DG) by SW620 colonic tumor cells was measured before and 8, 16, 24, and 48 h after treatment with the novel platinum drug oxaliplatin and the novel thymidylate synthase inhibitor Tomudex. Glucose transport was determined by measuring the initial rate of uptake of the nearly nonmetabolized glucose analog 3-O-methyl-D-[1-(3)H]glucose (3H-OMG). The effect of these drugs on cell cycle kinetics was determined using flow cytometry. RESULTS: Treatment of SW620 cells with oxaliplatin was found to decrease uptake of 3H-DG after up to 24 h, but uptake returned to control levels after longer treatment. The initial decrease in 3H-DG incorporation was associated with a lower rate of glucose transport. Treatment of cells with Tomudex induced an increase in 3H-DG uptake that depended on treatment duration. Both glucose transport and the volume of distribution of 3H-OMG were higher in Tomudex-treated cells than in control cells. Flow cytometry showed that oxaliplatin induced a G2 and M arrest, whereas a buildup of cells in the S phase was associated with Tomudex treatment. Both treatments induced apoptosis in SW620 cells. CONCLUSION: Changes in uptake of DG by SW620 colonic tumor cells responding to therapy is specific to the drug type. Modulation of glucose transport was associated with changes in 3H-DG uptake.