When to Do Surgery and When Not to Do Surgery for Endometriosis: A Systematic Review and Meta-analysis.

OBJECTIVE: We performed a systematic review and meta-analysis with the aim to answer whether operative laparoscopy is an effective treatment in a woman with demonstrated endometriosis compared with alternative treatments. Moreover, we aimed to assess the risks of operative laparoscopy compared with those of alternatives. In addition, we aimed to systematically review the literature on the impact of patient preference on decision making around surgery. DATA SOURCES: We searched MEDLINE, Embase, PsycINFO, ClinicalTrials.gov, CINAHL, Scopus, OpenGrey, and Web of Science from inception through May 2019. In addition, a manual search of reference lists of relevant studies was conducted. METHODS OF STUDY SELECTION: Published and unpublished randomized controlled trials (RCTs) in any language describing a comparison between surgery and any other intervention were included, with particular reference to timing and its impact on pain and fertility. Studies reporting on keywords including, but not limited to, endometriosis, laparoscopy, pelvic pain, and infertility were included. In the anticipated absence of RCTs on patient preference, all original research on this topic was considered eligible. TABULATION, INTEGRATION, AND RESULTS: In total, 1990 studies were reviewed. Twelve studies were identified as being eligible for inclusion to assess outcomes of pain (n = 6), fertility (n = 7), quality of life (n = 1), and disease progression (n = 3). Seven studies of interest were identified to evaluate patient preferences. There is evidence that operative laparoscopy may improve overall pain levels at 6 months compared with diagnostic laparoscopy (risk ratio [RR], 2.65; 95% confidence interval [CI], 1.61-4.34; p <.001; 2 RCTs, 102 participants; low-quality evidence). Because the quality of the evidence was very low, it is uncertain if operative laparoscopy improves live birth rates. Operative laparoscopy probably yields little or no difference regarding clinical pregnancy rates compared with diagnostic laparoscopy (RR, 1.29; 95% CI, 0.99-1.92; p = .06; 4 RCTs, 624 participants; moderate-quality evidence). It is uncertain if operative laparoscopy yields a difference in adverse outcomes when compared with diagnostic laparoscopy (RR, 1.98; 95% CI, 0.84-4.65; p = .12; 5 RCTs, 554 participants; very-low-quality evidence). No studies reported on the progression of endometriosis to a symptomatic state or progression of extent of disease in terms of volume of lesions and locations in asymptomatic women with endometriosis. We found no studies that reported on the timing of surgery. No quantitative or qualitative studies specifically aimed at elucidating the factors informing a woman's choice for surgery were identified. CONCLUSION: Operative laparoscopy may improve overall pain levels but may have little or no difference with respect to fertility-related or adverse outcomes when compared with diagnostic laparoscopy. Additional high-quality RCTs, including comparing surgery to medical management, are needed, and these should report adverse events as an outcome. Studies on patient preference in surgical decision making are needed (International Prospective Register of Systematic Review registration number: CRD42019135167).

Laparoscopic surgery for endometriosis.

BACKGROUND: Endometriosis is the presence of endometrial glands or stroma in sites other than the uterine cavity and is associated with pain and subfertility. Surgical interventions aim to remove visible areas of endometriosis and restore the anatomy. OBJECTIVES: To assess the effectiveness and safety of laparoscopic surgery in the treatment of painful symptoms and subfertility associated with endometriosis. SEARCH METHODS: This review has drawn on the search strategy developed by the Cochrane Menstrual Disorders and Subfertility Group including searching CENTRAL, MEDLINE, EMBASE, PsycINFO, and trial registries from inception to July 2013. SELECTION CRITERIA: Randomised controlled trials (RCTs) were selected in which the effectiveness and safety of laparoscopic surgery used to treat pain or subfertility associated with endometriosis was compared with any other laparoscopic or robotic intervention, holistic or medical treatment or diagnostic laparoscopy only. DATA COLLECTION AND ANALYSIS: Selection of studies, assessment of trial quality and extraction of relevant data were performed independently by two review authors with disagreements resolved by a third review author. The quality of evidence was evaluated using GRADE methods. MAIN RESULTS: Ten RCTs were included in the review. The studies randomised 973 participants experiencing pain or subfertility associated with endometriosis. Five RCTs compared laparoscopic ablation or excision versus diagnostic laparoscopy only. Two RCTs compared laparoscopic excision versus diagnostic laparoscopy only. Two RCTs compared laparoscopic excision versus ablation. One RCT compared laparoscopic ablation versus diagnostic laparoscopy and injectable gonadotropin-releasing hormone analogue (GnRHa) (goserelin) with add-back therapy. Common limitations in the primary studies included lack of clearly-described blinding, failure to fully describe methods of randomisation and allocation concealment, and risk of attrition bias.Laparoscopic surgery was associated with decreased overall pain (measured as 'pain better or improved') compared with diagnostic laparoscopy, both at six months (odds ratio (OR) 6.58, 95% CI 3.31 to 13.10, 3 RCTs, 171 participants, I(2) = 0%, moderate quality evidence) and at 12 months (OR 10.00, 95% CI 3.21 to 31.17, 1 RCT, 69 participants, low quality evidence). Compared with diagnostic laparoscopy, laparoscopic surgery was also associated with an increased live birth or ongoing pregnancy rate (OR 1.94, 95% CI 1.20 to 3.16, P = 0.007, 2 RCTs, 382 participants, I(2) = 0%, moderate quality evidence) and increased clinical pregnancy rate (OR 1.89, 95% CI 1.25 to 2.86, P = 0.003, 3 RCTs, 528 participants, I(2) = 0%, moderate quality evidence). Two studies collected data on adverse events (including infection, vascular and visceral injury and conversion to laparotomy) and reported no events in either arm. Other studies did not report this outcome. The similar effect of laparoscopic surgery and diagnostic laparotomy on the rate of miscarriage per pregnancy was imprecise (OR 0.94, 95% CI 0.35 to 2.54, 2 studies, 112 women, moderate quality evidence).When laparoscopic ablation was compared with diagnostic laparoscopy plus medical therapy (GnRHa plus add-back therapy), more women in the ablation group reported that they were pain free at 12 months (OR 5.63, 95% CI 1.18 to 26.85, 1 RCT, 35 participants, low quality evidence).The difference between laparoscopic ablation and laparoscopic excision in the proportion of women reporting overall pain relief at 12 months on a VAS 0 to 10 pain scale was 0 (95% CI -1.22 to 1.22, P = 1.00, 1 RCT, 103 participants, low quality evidence). AUTHORS' CONCLUSIONS: There is moderate quality evidence that laparoscopic surgery to treat mild and moderate endometriosis reduces overall pain and increases live birth or ongoing pregnancy rates. There is low quality evidence that laparoscopic excision and ablation were similarly effective in relieving pain, although there was only one relevant study. More research is needed considering severe endometriosis, different types of pain associated with endometriosis (for example dysmenorrhoea (pain with menstruation)) and comparing laparoscopic interventions with holistic and medical interventions. There was insufficient evidence on adverse events to allow any conclusions to be drawn regarding safety.

Spin-dependent electron transmission through bacteriorhodopsin embedded in purple membrane.

Spin-dependent photoelectron transmission and spin-dependent electrochemical studies were conducted on purple membrane containing bacteriorhodopsin (bR) deposited on gold, aluminum/aluminum-oxide, and nickel substrates. The result indicates spin selectivity in electron transmission through the membrane. Although the chiral bR occupies only about 10% of the volume of the membrane, the spin polarization found is on the order of 15%. The electrochemical studies indicate a strong dependence of the conduction on the protein's structure. Denaturation of the protein causes a sharp drop in the conduction through the membrane.

Target-specific, histology-independent, randomized discontinuation study of lapatinib in patients with HER2-amplified solid tumors.

BACKGROUND: To explore the activity of lapatinib with a novel trial design focused on the drug target rather than on histology. METHODS: Patients with HER2 amplified gastro-esophageal, bladder, ovarian, or uterine tumors were enrolled into a double-blinded randomized discontinuation study of lapatinib 1,500 mg PO daily. The planned sample size was 250 patients with HER2 amplified tumors, with the goal of randomizing 100 patients with stable disease (SD) at week 12 to either lapatinib or placebo. Patients responding after 12 weeks continued on lapatinib; those who progressed were discontinued from study. The primary objectives were response rate after 12 weeks and the percentage of patients who remained progression free 12 weeks after randomization to placebo versus lapatinib. Secondary objectives were duration of response and determination of the incidence of HER2 amplification in multiple tumor types. RESULTS: A total of 141 patients were screened and 32 patients with HER2 amplified tumors were enrolled. At week 12, 1 (3%) patient had a complete response, 9 (28%) had stable disease, 20 (63%) had progressive disease, and 2 (6%) were unknown. Only 7 patients with SD underwent randomization. The low response rate coupled with slow screening and enrollment led to early study closure. CONCLUSIONS: Basing trial eligibility on the presence of a genetic target, versus histologic classification, is challenging. While HER2 amplifications appear to be prevalent in select non-breast tumors, lapatinib monotherapy is associated with modest activity. The target-specific histology-independent randomized discontinuation design still merits consideration for targets clearly implicated in "oncogene addiction".

Spin specific electron conduction through DNA oligomers.

Spin-based properties, applications, and devices are commonly related to magnetic effects and to magnetic materials. Most of the development in spintronics is currently based on inorganic materials. Despite the fact that the magnetoresistance effect has been observed in organic materials, until now spin selectivity of organic based spintronics devices originated from an inorganic ferromagnetic electrode and was not determined by the organic molecules themselves. Here we show that conduction through double-stranded DNA oligomers is spin selective, demonstrating a true organic spin filter. The selectivity exceeds that of any known system at room temperature. The spin dependent resistivity indicates that the effect cannot result solely from the atomic spin-orbit coupling and must relate to a special property resulting from the chirality symmetry. The results may reflect on the importance of spin in determining electron transfer rates through biological systems.

Potential cures for endometriosis.

Treatment of endometriosis usually requires highly individualized management and varies depending on the presenting symptoms and the life stage of the patient. Surgical treatment of endometriosis starts with clinical recognition of the condition that may be enhanced by narrow band imaging. Surgery is effective in pain control and enhancing fertility. Tubal ligation or salpingectomy can be considered. Robotic surgery is unlikely to create a cure, but may assist surgery. Medical treatment including aromatase inhibitors may also be effective. Tubal flushing with lipiodol increases fecundity; other immunomodulators and neuromodulators may also be effective. Complementary therapies, however, have not been subjected to randomized clinical trials. Environmental factors, diet, and lifestyle modification may be effective.

How isolated are the electronic states of the core in core/shell nanoparticles?

We investigated how isolated are the electronic states of the core in a core-shell (c/s) nanoparticles (NPs) from the surface, when the particles are self-assembled on Au substrates via a dithiol (DT) organic linker. Applying photoemission spectroscopy the electronic states of CdSe core only and CdSe/ZnS c/s NPs were compared. The results indicate that in the c/s NPs the HOMO interacts strongly with electronic states in the Au substrate and is pinned at the same energies, relative to the Fermi level, as the core only NPs. When the capping molecules of the NPs were replaced with thiolated molecules, an interaction between the thiol groups and the electronic states of the NPs was observed that depends on the properties of the NPs studied. Thiols binding to the NPs induce the formation of surface trap states. However, while for the core only CdSe NPs the LUMO states are strongly coupled to the surface traps, independent of their size, this coupling is size dependent in the case of the CdSe/ZnS c/s NPs. For a large core, the LUMO is decoupled from the surface trap states. When the core is small enough, the LUMO is delocalized and interacts with these states.

Cooperative effect in the electronic properties of human telomere sequence.

The contribution of sequence elements of human telomere DNA to the interaction of DNA with electrons has been analyzed. By applying wavelength dependent low-energy photoelectron transmission and two-photon photoemission spectroscopy, we investigated the density of states of DNA oligomers with partial sequence elements of the human telomere assembled as monolayers on gold. The findings demonstrate the role of the resonance states in the DNA in accepting electrons and the effect of the sequence on these states. When guanine (G) bases are clustered together, the resonance negative ion state is stabilized, as compared to oligomers containing the same number of G bases but distributed within the sequence. The electron-capturing probability of the human telomere-like oligomer, a sequence with an additional single adenine (A) base adjacent to the G cluster, is dramatically enhanced compared to the other oligomers studied, most likely due to the enhancement of the density of states near the highest occupied molecular orbital.

Randomized phase II multicenter trial of two schedules of lapatinib as first- or second-line monotherapy in patients with advanced or metastatic non-small cell lung cancer.

PURPOSE: This randomized phase II study was initially designed to test the activity of two dose schedules of lapatinib (GW572016H), an oral, reversible, dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human EGFR-2 (HER2/neu; HER2), in chemotherapy-naive patients with non-small cell lung cancer (NSCLC); it was later amended to target patients with bronchioloalveolar carcinoma or no smoking history. EXPERIMENTAL DESIGN: Patients with good performance status and recurrent or metastatic NSCLC were randomized to lapatinib (orally, 1,500 mg once daily or 500 mg twice daily) until progression or intolerance. Patients could have had a maximum of one prior systemic therapy (chemotherapy or biological therapy) for NSCLC. Safety and activity were assessed every 4 and 8 weeks, respectively. Tumors were analyzed for EGFR and HER2 mutations and/or amplifications. RESULTS: Of 75 patients in the nontargeted population, 1 (1.3%) had partial response and 16 (21%) had stable disease of >or=24 weeks. No complete or partial responses were observed in 56 patients in the targeted population; 14 (25%) had stable disease of >or=24 weeks. No responses were seen in three patients with EGFR mutations and five with EGFR gene amplification. No mutations in HER2 were found. One of two patients with HER2 amplification had a 51% decrease in tumor size; however, this response was unconfirmed. The most common adverse events were grade 1 or 2 diarrhea, rash, fatigue, nausea, and anorexia. Adverse events were similar across dosing regimens. CONCLUSIONS: Lapatinib was well tolerated, with no notable difference in toxicity between treatment groups. Lapatinib monotherapy did not induce a significant number of tumor regressions in NSCLC. Further studies may be warranted to determine whether lapatinib is active in combination with other agents in the treatment of NSCLC.

Laparoscopic surgery for subfertility associated with endometriosis.

BACKGROUND: Endometriosis is the presence of endometrial glands or stroma in sites other than the uterine cavity. It is variable in both its surgical appearance and clinical manifestation, often with poor correlation between the two. Surgical treatment of endometriosis aims to remove visible areas of endometriosis and restore anatomy by the division of adhesions. OBJECTIVES: To assess the efficacy of laparoscopic surgery in the treatment of subfertility associated with endometriosis. The review aims to compare outcomes of laparoscopic surgical interventions compared to no treatment or medical treatment with regard to improved fertility. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of trials (June 2009), Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 2), MEDLINE (1966 to June 2009), EMBASE (1980 to June 2009), and reference lists of articles. SELECTION CRITERIA: Trials were selected if they were randomised and compared the effectiveness of laparoscopic surgery in the treatment of subfertility associated with endometriosis versus other treatment modalities or placebo. DATA COLLECTION AND ANALYSIS: Two studies were eligible for inclusion within the review. Both studies compared laparoscopic surgical treatment of minimal and mild endometriosis compared with diagnostic laparoscopy only. The recorded outcomes included live birth, pregnancy, fetal losses, and complications of surgery. MAIN RESULTS: When combining live birth rate and ongoing pregnancy after 20 weeks, meta-analysis demonstrated an advantage of laparoscopic surgery when compared to diagnostic laparoscopy only. The odds ratio (OR) was 1.64 (95% confidence interval (Cl) 1.05 to 2.57) in favour of laparoscopic surgery. Meta-analysis also demonstrated an advantage of laparoscopic surgery when compared to diagnostic laparoscopy only in terms of clinical pregnancy rates, with an OR of 1.66 (95% Cl 1.09 to 2.51) favouring laparoscopic surgery. The results still need to be interpreted with caution as Marcoux 1997 reported a large positive effect of surgery whereas Gruppo Italiano reported a small negative effect. When considering fetal losses, meta-analysis did not demonstrate an effect of laparoscopic surgery when compared to diagnostic laparoscopy only. The OR was 1.33 (95% Cl 0.60 to 2.94) favouring diagnostic laparoscopy only. AUTHORS' CONCLUSIONS: The use of laparoscopic surgery in the treatment of subfertility related to minimal and mild endometriosis may improve future fertility.

Laparoscopic surgery for pelvic pain associated with endometriosis.

BACKGROUND: Endometriosis is the presence of endometrial glands or stroma in sites other than the uterine cavity. It is variable in both its surgical appearance and clinical manifestation often with poor correlation between the two. Surgical treatment of endometriosis aims to remove visible areas of endometriosis and restore anatomy by division of adhesions and relieve painful symptoms. OBJECTIVES: To assess the efficacy of laparoscopic surgery in the treatment of pelvic pain associated with endometriosis. SEARCH STRATEGY: For the update in July 2009 we searched the Cochrane Menstrual Disorders and Subfertility Group's specialised register of trials (searched July 2009), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 2, 2009), MEDLINE (1966 July 2009), EMBASE (1980 July 2009), and reference lists of articles. SELECTION CRITERIA: Randomised controlled trials were selected comparing the effectiveness of laparoscopic surgery used to treat pelvic pain associated with endometriosis, with other treatment modalities or diagnostic laparoscopy only. DATA COLLECTION AND ANALYSIS: Assessment of trial quality and extraction of relevant data was performed independently by two reviewers. MAIN RESULTS: Five studies were included in the meta-analysis, including three full papers and two conference reports. All the randomised controlled trials with the exception of Lalchandani 2003 compared different laparoscopic surgical techniques with diagnotic laparoscopy only. Lalchandani 2003 compared laparoscopic coagulation therapy with diagnostic laparoscopy and medical treatment. Three studies (Abbott 2004; Sutton 1994; Tutunaru 2006) reported the pain scores six months post operatively. Meta-analysis demonstrated an advantage of laparoscopic surgery when compared to diagnostic laparoscopy only (OR of 5.72 95%Cl 3.09 to 10.60 ; 171 participants, three trials, Analysis 1.1). A single study (Tutunaru 2006) reported pain scores twelve months after the procedure. Analysis demonstrated an advantage of laparoscopic surgery when compared to diagnostic laparoscopy only (OR of 7.72 95%Cl 2.97 to 20.06 ; 33 participants, one trial, Analysis 1.1). AUTHORS' CONCLUSIONS: Laparoscopic surgery results in improved pain outcomes when compared to diagnostic laparoscopy alone. There were few women diagnosed with severe endometriosis included in the meta-analysis and therefore any conclusions from this meta-analysis regarding treatment of severe endometriosis should be made with caution. It is not possible to draw conclusions from the meta-analysis which specific laparoscopic surgical intervention is most effective.

Electronic structure of DNA--unique properties of 8-oxoguanosine.

8-Oxo-7,8-dihydroguanosine (8-oxoG) is among the most common forms of oxidative DNA damage found in human cells. The question of damage recognition by the repair machinery is a long standing one, and it is intriguing to suggest that the mechanism of efficiently locating damage within the entire genome might be related to modulations in the electronic properties of lesions compared to regular bases. Using laser-based methods combined with organizing various oligomers self-assembled monolayers on gold substrates, we show that indeed 8-oxoG has special electronic properties. By using oligomers containing 8-oxoG and guanine bases which were inserted in an all thymine sequences, we were able to determine the energy of the HOMO and LUMO states and the relative density of electronic states below the vacuum level. Specifically, it was found that when 8-oxoG is placed in the oligomer, the HOMO state is at higher energy than in the other oligomers studied. In contrast, the weakly mutagenic 8-oxo-7,8-dihydroadenosine (8-oxoA) has little or no effect on the electronic properties of DNA.

Phase II study of predictive biomarker profiles for response targeting human epidermal growth factor receptor 2 (HER-2) in advanced inflammatory breast cancer with lapatinib monotherapy.

PURPOSE: Inflammatory breast cancer (IBC) is one of the most aggressive forms of breast cancer. Lapatinib, an oral reversible inhibitor of epidermal growth factor receptor (EGFR) and human EGFR 2 (HER-2), demonstrated clinical activity in four of five IBC patients in phase I trials. We conducted a phase II trial to confirm the sensitivity of IBC to lapatinib, to determine whether response is HER-2 or EGFR dependent, and to elucidate a molecular signature predictive of lapatinib sensitivity. PATIENTS AND METHODS: Our open-label multicenter phase II trial (EGF103009) assessed clinical activity and safety of lapatinib monotherapy in patients with recurrent or anthracycline-refractory IBC. Patients were assigned to cohorts A (HER-2-overexpressing [HER-2+]) or B(HER-2-/EGFR+) and fresh pretreatment tumor biopsies were collected. RESULTS: Forty-five patients (30 in cohort A; 15 in cohort B) received lapatinib 1,500 mg once daily continuously. Clinical presentation and biomarker analyses demonstrated a tumor molecular signature consistent with IBC. Lapatinib was generally well tolerated, with primarily grade 1/2 skin and GI toxicities. Fifteen patients (50%) in cohort A had clinical responses to lapatinib in skin and/or measurable disease (according to Response Evaluation Criteria in Solid Tumors) compared with one patient in cohort B. Within cohort A, phosphorylated (p) HER-3 and lack of p53 expression predicted for response to lapatinib (P < .05). Tumors coexpressing pHER-2 and pHER-3 were more likely to respond to lapatinib (nine of 10 v four of 14; P = .0045). Prior trastuzumab therapy and loss of phosphate and tensin homolog 10 (PTEN) did not preclude response to lapatinib. CONCLUSION: Lapatinib is well tolerated with clinical activity in heavily pretreated HER-2+, but not EGFR+/HER-2-, IBC. In this study, coexpression of pHER-2 and pHER-3 in tumors seems to predict for a favorable response to lapatinib. These findings warrant further investigation of lapatinib monotherapy or combination therapy in HER-2+ IBC.

Cancer cell lines as genetic models of their parent histology: analyses based on array comparative genomic hybridization.

Tumor-derived cell lines are used as in vitro cancer models, but their ability to accurately reflect the phenotype and genotype of the parental histology remains questionable, given the prevalence of documented cell line-specific cytogenetic changes. We have addressed the issue of whether copy number alterations seen in tumor-derived cell lines reflect those observed in studies of fresh tissue by carrying out a meta-analysis of array-based comparative genomic hybridization data that considers both copy number alteration frequencies and the occurrence of cancer gene amplifications and homozygous deletions. Pairwise correlation comparisons between the data sets of seven diagnosis-specific matched tumor and cell line groups indicate that the trends in aberration frequencies are highly correlated between tumors and cell line sets of matched cancer histology relative to unmatched pairings. Despite their similarities, cell lines showed uniformly higher locus-specific alteration frequencies (P = 0.004) and several recurring cell line-specific alterations emerged. These include the previously documented losses of 13q and 9p and gains of 20q, as well as additional undescribed cell line-specific gains of 5p, 7p, and 17q and losses of 18q and 4q. These results indicate that, on average, cell lines preserve in vitro the genetic aberrations that are unique to the parent histology from which they were derived while acquiring additional locus-specific alterations. These data may enable a more predictive understanding of individual cell lines as in vitro models of cancer biology and therapy.

High resolution genomic analysis of sporadic breast cancer using array-based comparative genomic hybridization.

INTRODUCTION: Genomic aberrations in the form of subchromosomal DNA copy number changes are a hallmark of epithelial cancers, including breast cancer. The goal of the present study was to analyze such aberrations in breast cancer at high resolution. METHODS: We employed high-resolution array comparative genomic hybridization with 4,134 bacterial artificial chromosomes that cover the genome at 0.9 megabase resolution to analyze 47 primary breast tumors and 18 breast cancer cell lines. RESULTS: Common amplicons included 8q24.3 (amplified in 79% of tumors, with 5/47 exhibiting high level amplification), 1q32.1 and 16p13.3 (amplified in 66% and 57% of tumors, respectively). Moreover, we found several positive correlations between specific amplicons from different chromosomes, suggesting the existence of cooperating genetic loci. Queried by gene, the most frequently amplified kinase was PTK2 (79% of tumors), whereas the most frequently lost kinase was PTK2B (hemizygous loss in 34% of tumors). Amplification of ERBB2 as measured by comparative genomic hybridization (CGH) correlated closely with ERBB2 DNA and RNA levels measured by quantitative PCR as well as with ERBB2 protein levels. The overall frequency of recurrent losses was lower, with no region lost in more than 50% of tumors; the most frequently lost tumor suppressor gene was RB1 (hemizygous loss in 26% of tumors). Finally, we find that specific copy number changes in cell lines closely mimicked those in primary tumors, with an overall Pearson correlation coefficient of 0.843 for gains and 0.734 for losses. CONCLUSION: High resolution CGH analysis of breast cancer reveals several regions where DNA copy number is commonly gained or lost, that non-random correlations between specific amplicons exist, and that specific genetic alterations are maintained in breast cancer cell lines despite repeat passage in tissue culture. These observations suggest that genes within these regions are critical to the malignant phenotype and may thus serve as future therapeutic targets.

Continence mechanism after colpo-needle suspension for stress urinary incontinence.

OBJECTIVE: To determine the mechanism by which continence is restored following the colpo-needle suspension procedure. STUDY DESIGN: During 1990-1991, 37 women underwent colpo-needle suspension for stress urinary incontinence. Urodynamic investigation was performed preoperatively and 6-12 months postoperatively, and the results of these tests were compared in order to define the changes that might be responsible for the restoration of continence. RESULTS: In comparing the preoperative and postoperative cystometric and uroflowmetric measurements, we found no significant differences in the values for bladder capacity, residual volume pressure rise on filling or standing, maximal urethral voiding pressure or peak flow rates. The urethral pressure profiles at rest did not result in statistically significant differences regarding urethral length or urethral pressure. The only such differences postoperatively were elevation of pressure. Transmission ratios on coughing and in the proximal half of the urethra were Q1, 100.3 (P < .001), and Q2, 100.4 (P < .002), respectively. CONCLUSION: Colposuspension appears to correct genuine stress incontinence by repositioning the proximal urethra in the intraabdominal pressure zone, causing restoration of positive pressure transmission to the proximal urethra.

Ureteric jet examination by color Doppler ultrasound versus IVP for the assessment of ureteric patency following pelvic surgery--a pilot study.

During the study period 228 women underwent major gynecological surgery in our department. Of these, 25 were selected for the study because of suspected post-operative ureteric obstruction. Post-operatively, both intravenous pyelography (IVP) and ureteric jet examination by the means of color Doppler ultrasound were performed in the study group. The aims were to exclude iatrogenic ureteric occlusion and to test the reliability of ureteric jet examination with ultrasound, as compared with IVP, as a diagnostic test for ureteric obstruction. In 19 patients both IVP and jet examination were normal. In the remaining six patients, jet was negative either uni- or bi-laterally. Of these six, only two obstructions were diagnosed using IVP. This test was associated with a positive predictive value of 33.3%, negative predictive value of 100%, sensitivity of 100%, specificity of 88.6%, false negative of 0% and a false positive of 17.4%. It is concluded that the results suggest that color Doppler ultrasound may be a good screening test for ureteric occlusion following pelvic surgery. Whenever a jet test is negative, further evaluation by IVP is required.