The complexity of EGFR exon 19 deletion and L858R mutant cells as assessed by proteomics, transcriptomics, and metabolomics.

Most lung adenocarcinoma-associated EGFR tyrosine kinase mutations are either an exon 19 deletion (19Del) or L858R point mutation in exon 21. Although patients whose tumors contain either of these mutations exhibit increased sensitivity to tyrosine kinase inhibitors, progression-free and overall survival appear to be longer in patients with 19Del than in those with L858R. In mutant-transfected Ba/F3 cells, 19Del and L858R were compared by multi-omics analyses including proteomics, transcriptomics, and metabolomics. Proteome analysis identified increased plastin-2, TKT, PDIA5, and ENO1 expression in L858R cells, and increased EEF1G expression in 19Del cells. RNA sequencing showed significant differences between 19Del and L858R cells in 112 genes. Metabolome analysis showed that amino acids, adenylate, guanylate, NADPH, lactic acid, pyruvic acid glucose 6-phosphate, and ribose 5-phosphate were significantly different between the two mutant cells. Because GSH was increased with L858R, we combined osimertinib with the GSH inhibitor buthionine sulfoximine in L858R cells and observed synergistic effects. The complexity of EGFR 19Del and L858R mutant cells was demonstrated by proteomics, transcriptomics, and metabolomics analyses. Therapeutic strategies for lung cancer with different EGFR mutations could be considered because of their different metabolic phenotypes.

Is transvaginal mesh surgery with polytetrafluoroethylene mesh ORIHIME® feasible for anterior pelvic organ prolapse?-Randomized comparative study between ORIHIME® and Polyform™.

OBJECTIVE: Transvaginal mesh surgery for pelvic organ prolapse has been widely performed in Japan, but polypropylene mesh has not been used in Japan since the ban on TVM using polypropylene mesh in the United States. Currently, polytetrafluoroethylene mesh ORIHIME® is the only mesh available for TVM in Japan. Although polytetrafluoroethylene is a safe material, its low coefficient of friction and insufficient adhesion to the surrounding tissue make it difficult to maintain the mesh position when it is used in the transvaginal mesh surgery. The aim of this study was to evaluate the feasibility of TVM-A2 using ORIHIME®. METHODS: One hundred cases of TVM-A2 were included in the study. The patients were randomly assigned to two groups: the ORIHIME® group (Group O) and the PolyformTM group (Group P). With 50 patients in each group, the complications and recurrences up to the fourth year were compared. Surgeries were performed using the TVM-A2 method. Statistical analysis was performed using EZR. RESULTS: There were no significant differences in baseline parameters between the two groups. We observed no perioperative complications, and saw one case of postoperative abscess formation in Group O, which resolved successfully after incision and drainage. The 4-year recurrence rate was significantly higher in Group O. CONCLUSION: As the recurrence rate was significantly higher in Group O, we conclude that TVM-A2 using ORIHIME® which is the same procedure as TVM-A2 using polypropylene mesh is not feasible in repairing the pelvic organ prolapse.

Investigation of predictive factors for the presence of voiding dysfunction after transvaginal mesh surgery-Can the flow curve shape on uroflowmetry be a predictor?

PURPOSE: This study established the prognostic significance of the uroflowmetry flow curve shape in the presence of voiding dysfunction following transvaginal mesh surgery. METHODS: This is a retrospective study of 439 symptomatic cystocele patients who underwent anterior wall repair with transvaginal mesh surgery. Uroflowmetry and postvoid residual were used to evaluate voiding function both preoperatively and 12 months postoperatively. The patients were divided into two groups: those with and without postoperative voiding dysfunction, and the predictors of postoperative voiding dysfunction were analyzed. The shape of the urine flow curve was analyzed for its influence on the presence of postoperative voiding dysfunction. RESULTS: Thirty-five participants were in the voiding dysfunction group, while 404 were in the nonvoiding dysfunction group. Multivariate analysis was conducted by adding an interrupted-shaped curve to age, Qmax, and postvoid residual, which showed significant differences in univariate analysis, found that age 68 years or older (odds ratio [OR]: 7.68, 95%CI 1.02-58, p = 0.048), postvoid residual ≥110 mL (OR: 2.8, 95%CI 1.25-6.29, p = 0.013) and interrupted-shaped curve (OR: 2.47, 95%CI 1.07-5.69, p = 0.034) were discovered to be independent risk factors for the presence of voiding dysfunction after transvaginal mesh surgery. CONCLUSIONS: Following transvaginal mesh surgery for cystocele, three variables were found to be predictive of voiding dysfunction: the old age, excessive postvoid residual, and an interrupted-shaped flow curve. The uroflowmetry flow curve shape has the potential to be a new predictor of postoperative voiding dysfunction.

Targeting ROR1 in combination with osimertinib in EGFR mutant lung cancer cells.

Lung cancer that exhibits epidermal growth factor receptor (EGFR) gene mutation is sensitive to EGFR-tyrosine kinase inhibitors (TKIs), such as osimertinib. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) may be involved in overcoming EGFR-TKI resistance. Growth inhibition, colony formation, apoptosis, and mRNA/protein levels in four osimertinib-sensitive and resistant cell lines transfected with small interfering RNA (siRNA) targeting ROR1 (siROR1) were evaluated. Cell growth and colony formation were suppressed and apoptosis was increased in all cell lines treated with siROR1. Although EGFR, AKT, and ERK phosphorylation were not suppressed in all cell lines, TGF-ß2, AXL, CDH2, PARP1, PEG10, and TYMS mRNA expression levels were reduced. The combination of osimertinib with siROR1 was effective for the four cell lines, particularly in the two osimertinib-sensitive lines. In conclusion, targeting ROR1 in combination with osimertinib in EGFR mutant lung cancer may be a novel therapeutic option.

Are anterior mesh arms necessary in Japanese-style transvaginal mesh surgery for cystocele?

AIM: In this study, we retrospectively analyzed the medium-term efficacy and safety of surgery with transobturator two-arm transvaginal mesh for cystocele and to verify whether the anterior arms are necessary for Japanese-style transvaginal mesh surgery. METHODS: The study included 203 patients with cystocele who underwent transobturator two-arm transvaginal mesh at our hospital between August 2015 and June 2017 and received appropriate follow-up care for at least 48 months after surgery. RESULTS: The Pelvic Organ Prolapse Quantification stage was III in all the patients. Intraoperative complications included two cases of bladder injury and one case of more than 200 mL of blood loss. The mean observation period was 51.9 months, and prolapse recurred in the operated compartment in nine patients (4.4%). No cases of mesh exposure were observed. In comparing the preoperative characteristics of the 9 patients with prolapse recurrence at the surgical site with those of the other 194 patients, we found that the recurrence rate was significantly higher among patients in whom point Ba being 3.5 cm or more and among patients younger than 66 years. CONCLUSIONS: Transobturator two-arm transvaginal mesh for cystocele was as good and safe as the procedure previously reported with four-arm mesh; thus, it was possible to omit the anterior mesh arms in Japanese-style transvaginal mesh surgery. Patients should be informed preoperatively that prolapse recurs at a significantly higher rate among younger patients and in those whose point Ba being 3.5 cm or more.

Is transvaginal mesh procedure a potential measure for pelvic organ prolapse repair when performed by expert surgeons?

OBJECTIVES: The aim of this study was to verify the safety and efficacy of transvaginal mesh by analyzing the 2-year follow-up data of patients performed by a surgeon with a high volume of procedures. METHODS: A total of 617 patients with pelvic organ prolapse underwent transvaginal mesh by a single surgeon. Complications and anatomical status of each patient were examined up to 24 months after surgery. Risk factors for the recurrence were also analyzed. RESULTS: Regarding complications, we experienced 10 patients (3.8%) of bladder injuries in anterior transvaginal mesh and eight (3.4%) in anterior and posterior transvaginal mesh. Massive blood loss was observed in four patients, but there was no case of blood transfusion. Mesh exposures were seen in seven patients (1.2%). A total of 100 patients (16.2%) had prolapse recurrence, defined as the Pelvic Organ Prolapse Quantification System stage ≥II. As to recurrences on the operated compartments, we observed five patients (2.0%) for anterior transvaginal mesh, three (6.5%) for posterior transvaginal mesh, five (7.4%) for combined transvaginal mesh, and 31 (14.2%) in anterior and posterior transvaginal mesh. Regarding Point C before operation in the anterior and posterior transvaginal mesh, the recurrence rates were more than 23% in patients with a Point C of 4 or more. Binominal regression analyses showed that higher body mass index, younger age, and higher stage of uterine prolapse were significant risk factors. CONCLUSIONS: The transvaginal mesh surgery is safe when conducted by experts. However, the recurrence rate may exceed 20% for high-stage uterine prolapse even when conducted by experts.

Clinical Guidelines for Female Lower Urinary Tract Symptoms (second edition).

The present article is an abridged English translation of the Japanese Clinical Guidelines for Female Lower Urinary Tract Symptoms (second edition), published in September 2019. These guidelines consist of a total of 212 pages and are unique worldwide in that they cover female lower urinary tract symptoms other than urinary incontinence. They contain two algorithms for "primary treatment" and "specialized treatment," respectively. These guidelines, consisting of six chapters, address a total of 26 clinical questions including: (i) treatment algorithms; (ii) what are female lower urinary tract symptoms?; (iii) epidemiology and quality of life; (iv) pathology and illness; (v) diagnosis; and (vi) treatment. When the patient's symptoms mainly involve voiding and post-micturition symptoms, specialized treatment should be considered. In the event of voiding symptoms concurrent with storage symptoms, residual urine should be measured; if the residual urine volume is <100 mL, then diagnosis and treatment for storage symptoms is prioritized, and if the volume is ≥100 mL, then specialized treatment should be considered. When storage symptoms are the primary condition, then the patient is subject to the primary treatment algorithm. Specialized treatment for refractory overactive bladder includes botulinum toxin injection and sacral nerve stimulation. For stress urinary incontinence, surgical treatment is indicated, such as urethral slings. The two causes of voiding symptoms and post-micturition symptoms are lower urinary tract obstruction and detrusor underactivity (underactive bladder). Mechanical lower urinary tract obstruction, such as pelvic organ prolapse, is expected to improve with surgery.

Techniques of transvaginal mesh prolapse surgery in Japan, and the comparison of complication rates by surgeons' specialty and experience.

OBJECTIVES: To investigate techniques of transvaginal mesh prolapse surgery in Japan, and compare complication rates by surgeons' specialty and experience with transvaginal mesh prolapse surgery. METHODS: We carried out an anonymous questionnaire survey for surgeons attending a national transvaginal mesh prolapse surgery meeting in 2010. The surgeons were asked to state their specialty, practice patterns, transvaginal mesh prolapse surgery techniques and the number of transvaginal mesh prolapse procedures carried out as an operator including the complications that occurred. RESULTS: A total of 118 surgeons (59% of the attendees) responded to the questionnaire. The mean age was 44.0 ± 9.1 years, 54 (46%) were gynecologists and 64 (54%) were urologists. All urologists and 78% of gynecologists carried out anti-incontinence surgery (midurethral sling), whereas more gynecologists (93%) carried out native tissue repair than urologists (73%). Most of both specialties (each 98%) avoided prophylactic anti-incontinence surgery during prolapse surgery. Concomitant hysterectomy during transvaginal mesh prolapse surgery was generally avoided. Surgeons reached a consensus regarding the critical transvaginal mesh prolapse surgery techniques: hydrodissection (98%) and the full-thickness dissection (the "Lychee layer"; 69%). A total of 11 935 Prolift-type transvaginal mesh prolapse procedures were carried out and the following complications were reported: bladder injury (1.6%), rectal injury (0.3%), ureteral injury (0.1%), blood transfusion (0.2%), vaginal exposure (2.8%) and recurrence requiring reoperation (1.1%). Although complications did not differ between specialty, bladder injury, transfusion and vaginal exposure were less prevalent with experienced surgeons (≥50 transvaginal mesh prolapse surgery cases). CONCLUSIONS: Over 10 000 transvaginal mesh prolapse surgery had been carried out in Japan with a relatively low complication rate until 2010. This survey shows that surgeons' experience could lead to a decrease in the amount of transvaginal mesh prolapse surgery complications.

A nationwide surveillance of surgical site infection after mid-urethral slings in Japan.

We performed a questionnaire-based, retrospective, nationwide survey on perioperative management and antimicrobial prophylaxis for mid-urethral sling surgery for stress urinary incontinence in Japan to realize the clinical practice and risk factors for SSI. Records of women receiving transobturator tape (TOT) and tension-free vaginal tape (TVT) surgeries from 2010 to 2012 were obtained from hospitals belonging to the Japanese Society of Pelvic Organ Prolapse Surgery. The questionnaire addressed hospital volume, perioperative management, and SSI. Risk factors for SSI were investigated by comparing cases with and without SSI. The data from 97 hospitals and a total 1627 TOT and 1045 TVT surgeries were analyzed. Mean case volumes of TOT and TVT surgeries were 7.3 ± 14.9 and 7.1 ± 17.8 cases per year, respectively. Preoperative hair removal, bowel preparation, and urine culture were routinely performed at 44 (45.3%), 31 (32.0%), and 22 (22.7%) hospitals, respectively. First-generation (51.5%) or second-generation (34.0%) cephalosporin was mostly used for antimicrobial prophylaxis. SSI was reported only in 6 patients (0.22%) and none of them developed abscesses. None of the factors we could evaluate from the questionnaire were found to be significantly associated with SSI. SSI after mid-urethral slings rarely occurred in Japan (0.22%) and no parameters about perioperative managements significantly increased SSI. However, further studies with more detail information of each patient and operation are required to confirm their appropriate perioperative managements for mid-urethral slings.

Risk factors for surgical site infection after transvaginal mesh placement in a nationwide Japanese cohort.

AIMS: We conducted a nationwide survey on perioperative management and antimicrobial prophylaxis of transvaginal mesh surgeries for pelvic organ prolapse in Japan to understand the practice and risk factors for surgical site infection (SSI). METHODS: Health records of women undergoing tension-free vaginal mesh (TVM) surgeries from 2010 to 2012 were obtained from 135 medical centers belonging to the Japanese Society of Pelvic Organ Prolapse Surgery. The questionnaire addressed hospital volume, perioperative management, and SSI. Risk factors for SSI were investigated by comparing cases with and without SSI. RESULTS: The hospital volume among institutions varied from 0 to 248 per year (median 16.7). Preoperative hair removal, bowel preparation, and urine culture were routinely performed at 74 (55%), 66 (49%), and 24 (18%) hospitals, respectively. Prophylactic antimicrobials used were mostly first-generation (43%) or second-generation (42%) cephalosporin. SSI was reported in 86 of 9323 patients (0.92%). A multivariate analysis indicated lower hospital volume (odds ratio [OR], 0.995 [by 1-point increase]; P < 0.001), preoperative bowel preparation (OR, 2.08; P = 0.013), non-routine urine culture (OR, 3.00; P = 0.0006), and the use of antibiotics other than first-generation cephalosporin (OR, 5.29; P = 0.0011) as significant risk factors for SSI. In contrast, the cut-off points of hospital volume for preventing SSI was 116.7 cases (area under curve: 0.61). CONCLUSION: The prevalence of SSI in TVM surgeries was 0.92% in Japan. Lower hospital volume, bowel preparation, non-routine preoperative urine culture, and prophylactic antibiotics other than first-generation cephalosporin significantly elevated the incidence of SSI.

Predictors of persistent stress urinary incontinence after transvaginal mesh repair.

BACKGROUND: We evaluated the effect of transvaginal mesh (TVM) surgery for voiding function and continence using noninvasive examination and questionnaire. The present study aimed to ascertain which categories of patients need concomitant mid-urethral sling (MUS) after TVM surgery. METHODS: We included women who underwent TVM procedure between November 2009 and October 2013. Data from noninstrumented uroflowmetry and questionnaires about urinary symptoms were analyzed. RESULTS: The present study investigated the cases of 961 women who underwent TVM surgery. The persistence of stress urinary incontinence (SUI) was 57.6%. Almost all the parameters measured using uroflowmetry and questionnaires significantly improved in all types of urinary incontinence 12 months after surgery. A history of hysterectomy, preoperative high flow (corrected maximum flow rate > 1.5), and preoperative urge urinary incontinence were independent risk factors for the persistence of SUI. CONCLUSIONS: TVM for pelvic organ prolapse improved subjective and objective voiding function. Mixed urinary incontinence (MUI) patients with high urinary flow may be suitable for concomitant MUS with TVM because of the high level of SUI persistence.

Synergistic effect of pacritinib with erlotinib on JAK2-mediated resistance in epidermal gowth factor receptor mutation-positive non-small cell lung Cancer.

The combination effect of pacritinib, a novel JAK2/FLT3 inhibitor, with erlotinib, the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), on non-small cell lung cancer cells with EGFR activating mutations was investigated. The combination showed synergistic effects on JAK2-mediated EGFR TKI-resistant PC-9/ER3 cells in some cases. The combination markedly suppressed pAKT and pERK although pSTAT3 expression was similar regardless of treatment with the pacritinib, pacritinib + erlotinib, or control in PC-9/ER3 cells. Receptor tyrosine kinase array profiling demonstrated that pacritinib suppressed MET in the PC-9/ER3 cells. The combined treatment of pacritinib and erlotinib in PC-9/ER3 xenografts showed more tumor shrinkage compared with each drug as monotherapy. Western blotting revealed that pMET in tumor samples was inhibited. These results suggest MET suppression by pacritinib may play a role in overcoming the EGFR-TKI resistance mediated by JAK2 in the PC-9/ER3 cells. In conclusion, pacritinib combined with EGFR-TKI might be a potent strategy against JAK2-mediated EGFR-TKI resistance.

Fluoroscopic imaging of needle position in the tension-free vaginal mesh procedure for pelvic organ prolapse: two case reports.

The tension-free vaginal mesh (TVM) procedure has become one of the commonly used treatments for pelvic organ prolapse (POP) due to good clinical outcome. However, there are several technical difficulties associated with this procedure. We performed fluoroscopy for imaging of the surgical procedure on the TVM to resolve the technical problems regarding needle penetration. Fluoroscopic imaging with rectogram and cystogram demonstrated the positions of the needle, pelvic organs and index finger for needle guidance in the TVM procedure. Fluoroscopic imaging may be useful to understand the movement of surgical devices in the blind space, objectively evaluate the surgeon's skill, avoid injury to the pelvic organs, and detect any such injury immediately should it occur.

[Information tools utilized by outpatients presenting to a female urological clinic and their temporal trend: analysis of 3,480 patients].

OBJECTIVES: Female urological diseases, including pelvic organ prolapse and urinary incontinence, are common in elderly people, but public knowledge about these diseases is limited. We analyzed information tools that patients with female urological disease utilized to acquire information about their diseases. MATERIALS AND METHODS: This study included 3,480 patients who presented to our female urological clinic between January 2005 and December 2008. We conducted a questionnaire survey on what information tools were used for information gathering. RESULTS: The newspaper was the leading information tool (39.9%), followed by referral from another clinic (17.8%), internet (15.7%), TV (14.8%), recommendation by family or friends (5.5%), books or magazines (3.2%), and informative sessions for the public (0.6%). The temporal trend in the rate of information tool use over the 4 years showed that internet use increased significantly every year (p trend = 0.041) and was the most utilized tool in 2008, along with referral from other clinics. The rate of newspaper or TV use depended on their volumes of the female urological diseases. Additionally, no change over the study period was observed for the rate of internet utilization for patients in their 40s or under; however, it increased in patients in their 50s or over, and patients in their 50s and 60s utilized the internet as often as patients in their 40s or under in 2008. CONCLUSIONS: The newspaper was the most utilized information tool for patients with female urological diseases. However, internet use for gathering disease information is increasing, and the internet may be the most important information tool in the near future.

Transvaginal repair of enterocele following robot-assisted radical cystectomy using a mesh for abdominal wall hernia repair.

Introduction: This report aims to describe our experience in the pelvic floor reconstruction of anterior enterocele following radical cystectomy by transvaginal surgery using a mesh for abdominal wall hernia repair. Case presentation: An 84-years-old woman developed pelvic organ prolapse 4 months after undergoing robot-assisted radical cystectomy. After examination, she was diagnosed with a midline anterior enterocele. Considering the thinness of the vaginal wall and the large defect of the vaginal wall muscle layer, we performed transvaginal repair using a mesh for abdominal wall hernia repair designed to reduce the adhesion to the intestinal tract. Conclusion: At the 1-year follow-up, neither recurrence nor complications were observed. This showed that transvaginal mesh surgery for abdominal wall hernia repair could be a treatment option for pelvic organ prolapse with a vaginal wall muscle layer defect after radical cystectomy.

Basic procedures in tension-free vaginal mesh operation for pelvic organ prolapse.

A variety of tension-free vaginal mesh (TVM) systems are available for surgical treatment of pelvic organ prolapse (POP). These include Prolift, Apogee/Perigee and Avaulta, all of which vary in terms of mesh size, shape and surgical technique to such an extent that they cannot truly be considered the same operation for the purpose of evaluating results. I began carrying out self-made mesh cut out from Gynemesh PS in 2005. This system has four main characteristics: (i) the mesh is intended as a replacement for defective visceral pelvic fascia; (ii) it bridges between the left and right arcus tendineus fascia pelvis (white line, or ATFP); (iii) large-size mesh is held in place by passing cannulas through the obturator fascia (anterior wall) or the sacrospinous ligament (SSL) to attach the arms of the mesh graft; and (iv) the bladder neck is preserved. The mesh that I have used since then has been essentially similar to the Prolift System, developed by a French TVM group, in terms of size and shape of its central portion. Mesh grafts used for the anterior wall are quite large, so skillful execution will provide sufficient room between the left and right ATFP in almost all cases. This video discusses the fundamental techniques necessary for skillful execution of the tension-free vaginal mesh (TVM) procedure using the Prolift System, focusing on the following points: (i) surgical separation of the correct layers of the vaginal wall, and the area separated, and effective hemostasis; (ii) precise puncture technique, especially the second puncture for the anterior TVM (TVM-A) procedure and the sacrospinous ligament (SSL) puncture in the posterior TVM (TVM-P) procedure; (iii) firmly securing the mesh to the vaginal wall or cervical canal; and (iv) careful mesh placement and formation of a bridge between the left and right arcus tendineus fascia pelvis (ATFP). Proper separation of the vaginal wall layers, in particular, is crucial for preventing unnecessary blood loss and mesh erosion. The second puncture in the TVM-A is the most important of the puncture maneuvers for the procedure. Penetrating the tough tissue near the ischial spine represents a significant challenge, and the SSL penetration in the TVM-P procedure is unexpectedly difficult for those without sufficient experience. In order to become proficient, the surgeon must have hands-on experience under the supervision of experts. Finally, TVM is a relatively new procedure, so one must master the fundamentals before gaining true proficiency. The technique does not call for virtuosity on the part of the surgeon, but key points must be mastered to reduce the risk of complications and recurrences. With repeated hands-on training, surgical skills will gradually improve to the requisite level. This is a translated section of a video article originally published in Japanese as a DVD in the Audio-Visual Journal Vol.15 No.15. 2009 by The Japanese Urological Association.

Targeting ROR1 in combination with pemetrexed in malignant mesothelioma cells.

OBJECTIVE: Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is overexpressed in a subset of malignant cells. However, it remains unknown whether ROR1 is targetable in malignant mesothelioma (MM). Therefore, in this study, we investigated the effects of ROR1 inhibition in mesothelioma cells. MATERIALS AND METHODS: Growth inhibition, colony formation, apoptosis, and mRNA/protein levels using siRNA-transfected MM cells were evaluated. Cluster analysis using Gene Expression Omnibus repository of transcriptomic information was also performed. RESULTS: Our results indicated that in three (H2052, H2452, and MESO-1) among four MM cell lines, ROR1 inhibition had anti-proliferative and apoptotic effects and suppressed the activation of AKT and STAT3. Although growth inhibition by siROR1 was minimal in another mesothelioma cell line (H28), colony formation was significantly suppressed. Microarray, quantitative polymerase chain reaction, and Western blot analyses showed that there were differences in the suppression of mRNA and proteins between H2452 and H28 cells transfected with siROR1 compared with those transfected with control siRNA. Cluster analysis further showed that MM tumors had relatively high ROR1 expression, although the cluster in them was different from that in MM cell lines. Thymidylate synthase, a target of pemetrexed, was downregulated in H2452 cells transfected with siROR1. Accordingly, a combination of pemetrexed with siROR1 was found to be effective in the three MM cell lines we studied. CONCLUSION: Our findings may provide novel therapeutic insight into the treatment of advanced MM.

Increased vascular endothelial growth factor expression in patients with bladder pain syndrome/interstitial cystitis: its association with pain severity and glomerulations.

OBJECTIVE: To determine the angiogenic profiles in the bladder of patients with bladder pain syndrome (BPS)/interstitial cystitis (IC), and to evaluate the relationship between these profiles and associated clinical features including pelvic pain and glomerulations. PATIENTS AND METHODS: Angiogenesis and angiogenic components are important in chronic inflammatory disease. High levels of vascular endothelial growth factor (VEGF) have been shown to induce immature angiogenesis, where microvessels have insufficient coverage of pericytes, resulting in haemorrhagic vessels. Biopsy specimens from 30 patients with BPS/IC and glomerulations, and 10 control patients, were examined immunohistochemically for VEGF expression, microvessel density (MVD) and immature microvessels. Pericyte coverage of microvessels in the specimens was used as an indicator of mature microvessels, and pericytes were identified by double-immunohistochemistry for CD34 and alpha-smooth muscle actin. The microvessel pericyte coverage index (MPI) was calculated as the ratio of mature vessels to total vessels. We also assessed the relationship between these angiogenic profiles and associated clinical features including pain and glomerulations. RESULTS: VEGF expression in the lamina propria was significantly higher in BPS/IC than in control samples (50% vs 10%, P < 0.05). Among patients with BPS/IC, VEGF expression was significantly higher in those with severe pain than in those with mild pain (78% vs 38%, P < 0.05). The MPI was significantly lower in BPS/IC than in control samples (23% vs 35%, P < 0.05), whereas MVD did not differ significantly between BPS/IC and control samples. CONCLUSIONS: There is increased VEGF and immature vascularization in patients with BPS/IC, and VEGF expression is associated with the degree of pain described by patients. Taken together, VEGF might contribute to pain and promote the formation of immature vessels in BPS/IC, and the increased immature vascularization might have a role in glomerulations in patients with BPS/IC.

[Case of multiple encrusted stones on the ureteral stent left for 7 years: the efficacy of extracting the ureteral stent on transurethral lithotripsy].

A 48 years-old man had undergone transurethral lithotripsy (TUL) and Extracorporeal Shockwave Lithotripsy (ESWL) for bilateral ureteral stones and bilateral ureteral stents had been placed in 2001. He was lost to the follow-up for about 7 years after the removal of left ureteral stent. He had complained of right back pain and fever for two months. KUB showed right ureteral stones and encrustation along the ureteral stent. We performed TUL extracting the ureteral stent by silk, referring to silk loop technique. All stones and the encrusted ureteral stent were removed. This was very effective for patients with encrusted ureteral stent.

[Assessment of quality of life in women with pelvic organ prolapse: conditional translation and trial of P-QOL for use in Japan].

INTRODUCTION: A purpose of the surgical treatment for pelvic organ prolapse (POP) is not only the anatomical restoration of the patients but also the improvement of their quality of life (QOL). We have no linguistic validated questionnaire in Japanese to assess it. Therefore we have translated 'prolapse quality of life questionnaire (P-QOL)' into Japanese and present it to the thirty POP patients at our institute for evaluating mental and physical condition before and three months after the operation. PATIENTS AND METHODS: We completed SF-36 and a questionnaire of patients' satisfaction on 30 patients besides P-QOL. SF-36 stands for Medical Outcome Study, Short Form 36 and is used for assessing overall QOL. We also completed pelvic organ prolapse quatification (POP-Q) to evaluate physical condition of the patients. RESULTS: No recurrent case was observed at three months after the operation. QOL of the patients was much improved based on the results of P-QOL, SF-36 and POP-Q. The results of questionnaire of patients' satisfaction were well correlated with other questionnaires. CONCLUSION: P-QOL can be expected as the linguistic validated questionnaire in Japanese version. Further studies will be needed for making linguistic validated P-QOL in Japanese version.