Improving treatment and prevention of pelvic organ prolapse, a disorder affecting up to half of parous women, requires thorough mechanical analysis of the vagina and other endopelvic structures at the cellular level. In this study, we tested single vaginal smooth muscle cells (SMCs) to quantify their elastic moduli. Cells were enzymatically isolated from vaginal walls of freshly sacrificed, virgin Long Evans rats and cultured using well-established methods. A custom-built experimental setup was used to perform tensile tests. Micropipettes were fabricated to serve as cantilever-type load cells, which were coated in cellular adhesive. Two pipettes applied tension to SMCs until adhesion between the cell and a pipette failed. During mechanical testing, images of SMCs were collected and translated into strain and stress. Specifically, force/stress data were calculated using Euler-Bernoulli Beam Theory and by making simplifying geometric assumptions. The average initial and total elastic moduli (mean ± SEM) for single vaginal SMCs were 6.06 ± 0.26 kPa and 5.4 ± 0.24 kPa, respectively, which is within the range reported for other types of SMCs, mainly airway and vascular, of various species. This protocol can and will be applied to further investigate mechanics of single cells from the pelvic region with independent variables such as parity, age, body mass index, and various stages of POP. Results of these experiments will provide critical information for improving current treatments like drug therapies, surgical procedures, medical grafts and implants, and preventative practices like stretching and exercise techniques. / Master of Science

Made available in DSpace on 2015-07-22T20:50:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-11-25. Added 1 bitstream(s) on 2015-08-11T03:25:36Z : No. of bitstreams: 1 Publico-045.pdf: 1293717 bytes, checksum: aa77a18d9ad66fac463c08766304abf5 (MD5) / Objetivo: avaliar os resultados anatômicos, funcionais e complicações do tratamento do prolapso da parede vaginal anterior com tela de submucosa de intestino delgado suíno (SIS) e com colporrafia anterior. Pacientes e Métodos: estudo prospectivo e randomizado para comparação do uso de tela de SIS e de colporrafia tradicional. As mulheres foram avaliadas no pré-operatório e com seis meses após a cirurgia. Os parâmetros utilizados foram: sistema de quantificação do prolapso genital (POP-Q), questionário de qualidade de vida validado (P-QoL) e complicações. Os dados foram analisados pelo teste de Mann-Whitney e Qui-quadrado para avaliação da homogeneidade entre os grupos. A seguir, utilizamos o teste t-Student pareado ou teste t-Student de amostras independentes. O estudo foi aprovado pelo Comitê de Ética Local e registrado no ClinicalTrials com o número NCT00827528. Resultados: os resultados representam a análise de 29 pacientes no grupo com tela de SIS e 27 no grupo com colporrafia tradicional. Os grupos foram semelhantes consoante idade, índice de massa corpórea, paridade, estádio do prolapso, cirurgia prévia para prolapso, presença de incontinência urinária de esforço, pontuação no questionário de qualidade de vida e medidas dos pontos anatômicos no pré-operatório. Com seis meses de seguimento, a taxa de cura anatômica no grupo com tela foi de 86,2% comparada com 59,3% no grupo da colporrafia, pelo critério da Sociedade Internacional de Continência (ICS). Não houve diferença de sucesso anatômico entre as técnicas quando consideramos a subdivisão do estádio II. A média do ponto Ba, pré-operatória, no grupo com tela foi de +2,07 cm e +2,22 cm na colporrafia e, no pós-operatório, de -1,93 cm (p<0,001) e de -1,37 cm (p<0,001), respectivamente. O NNT (Número Necessário a Tratar) foi 4. Ambos os procedimentos melhoraram de forma significativa as medidas de qualidade de vida. Contudo, o grupo com tela não demonstrou diferença quando comparado ao da colporrafia tradicional. Houve 4 pacientes com sangramento excessivo no grupo SIS, embora nenhuma requereu hemotransfusão. Observamos maior número de complicações no grupo SIS (20 vs 9; p=0,01) e maior tempo cirúrgico (48,3 min ±16,1 vs 30,3min ±19,4; p=0,001). O tempo de internação hospitalar foi de 3,3 e 3,2 dias, respectivamente. Não houve casos de infecção ou de erosão da tela. Conclusão: As cirurgias para o prolapso genital resultam em melhora significativa da qualidade de vida. Observamos melhor cura anatômica do ponto Ba com tela, de acordo com o critério da ICS. Consoante os parâmetros de qualidade de vida não houve diferença entre as técnicas. Houve maior número de complicações no grupo com tela. / Objective: the aim of this study was to evaluate anatomical, functional results and complications of small intestine submucosa (SIS) graft compared to traditional anterior repair in surgical treatment of anterior vaginal wall prolapse. Methods: This is a randomized and prospective study to compare the SIS graft with traditional colporrhaphy (TC) in surgical treatment of anterior vaginal prolapse. Subjects were randomized to SIS (n=29) or to TC (n=27) and compared preoperatively and at 6 months postoperatively. We used pelvic organ quantification system (POP-Q), a validated prolapse quality of life questionnaire (P-QoL) and possible complications. Data were compared using the Mann–Whitney test or a chi-squared test to determine that there were no significant intergroup differences. This then enabled us to use the independent samples t-test or the paired Student’s t-test. This study was approved by Local Ethics Committee and register at ClinicalTrials NCT00827528. Results: the outcomes represent the analysis of 29 patients in SIS group and 27 in traditional repair. Both groups were paired by age, parity, body mass index, stage of anterior prolapse, previous surgery for prolapse, presence of incontinence, POP-Q measurements and quality of life preoperatively. At 6-month follow-up, SIS group have 86.2% anatomic cure comparing with 59.3% in traditional repair, using the International Continence Society (ICS) patterns. We did not report differences between the techniques when we divided the stage II. The mean point Ba preoperatively in SIS group was +2.07 cm and +2.22 cm in traditional repair and postoperatively -1.93 cm (p<0.001) and -1.37 cm (p<0.001), respectively. The NNT (Number Need to Treat) was 4. Both operations significantly improved prolapse quality-of-life severity measures. Although SIS group did not showed significant improvement in quality-of-life parameters measured in comparison to traditional repair. Excessive bleeding occurred in 4 patients in SIS group although none required blood transfusion. We reported more complications in SIS group (20 vs 9, p=0.01) and longer surgical time (48.3min ±16.1 vs 30.3min ±19.4; p=0.001). The average hospital length was 3.3 and 3.2 days, respectively. We did not reported infections or erosion of the mesh. Conclusions: Surgery for vaginal prolapse results in marked improvement in prolapse quality of life. We could see that SIS repair improved point Ba measurement significantly using the ICS patterns. Regarding quality-of-life parameters we did not observe significant differences in both techniques. / TEDE / BV UNIFESP: Teses e dissertações

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24135号 / 医博第4875号 / 新制||医||1060(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 近藤 尚己, 教授 川上 浩司, 教授 阪上 優 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Abstract Rectal prolapse and internal rectal prolapse with symptoms of obstructed defecation and/or faecal incontinence are debilitating conditions. Often, symptoms coexist from other pelvic compartments, reducing quality of life. Robot-assisted surgery with its advanced features may offer better conditions in narrow pelvic space to correct rectal prolapses with rectopexy operation. In this thesis, we compared robot-assisted and laparoscopic techniques during the early learning curve in a ‘matched-pairs’ feasibility study (n = 30, follow-up three months) and in a prospective randomized series (n = 33, follow-up 24 months). The long-term functional results were assessed in a retrospective multicenter study with cross-sectional questionnaire assessment (n = 508, median follow-up 44 months). In the randomised series, as demonstrated with MR defecography, ventral rectopexy corrects the posterior compartment defects, external and internal rectal prolapses and recto-enteroceles. The operation restores the posterior and middle compartment anatomy and reduces pelvic organ mobility with a minor impact on the anterior compartment. Pelvic floor dysfunction and symptom-specific quality of life is improved after rectopexy; specifically, the colorectal-anal and the pelvic organ prolapse subscales in the questionnaires showed improvement. We found equality between robot-assisted rectopexy and laparoscopic rectopexy in most relevant outcome measures, which does not justify the added cost of the routine use of robots in rectopexy operations. The health-related quality of life and cost-utility analysis in our cohort indicated, however, that in long-term the technique may be cost-effective. The functional results are retained in the long term. The rate of recurrences (7.1%) and complications (10%) are acceptable and mesh-related complications (1.4%) are rare. Denovo symptoms, such as the urge to defecate or urinary incontinence, may arise, while urinary symptoms may be alleviated. In the long-run, patients with external rectal prolapse benefit more than patients with internal rectal prolapse. In part, the results of this thesis support using a multidisciplinary approach in examining patients with posterior pelvic floor dysfunction. Furthermore, the indications for robotic use in rectopexy operations need to be explored in larger patient samples. / Tiivistelmä Rektumprolapsi ja peräsuolen sisäinen tuppeuma eli interni prolapsi aiheuttavat hankalia oireita, kuten ulostusvaikeuksia, ulosteinkontinenssia ja lantion kipua. Elämänlaatua heikentäviä oireita esiintyy usein samanaikaisesti myös muissa lantion osissa. Robottiavusteinen kirurgia tarjoaa paremmat leikkausolosuhteet lantion ahtaassa tilassa tehtävään rektopeksialeikkaukseen ja mahdollisesti edut voivat näkyä leikkaustuloksessa. Tässä väitöskirjassa vertailimme robottiavusteista ja laparoskooppista leikkaustekniikkaa oppimiskäyrän alkuvaiheessa käyttökelpoisuustutkimuksessa kaltaistetussa parivertailuasetelmassa (n = 40, seuranta-aika 3 kk) sekä prospektiivisessa randomoidussa tutkimussarjassa (n = 33, seuranta-aika 24 kk). Monikeskustutkimuksessa (n = 508, seuranta-ajan mediaani 44 kk) selvitimme laajassa aineistossa laparoskooppisen ventraalisen rektopeksian pitkäaikaistuloksia liittämällä aineiston analyysiin poikkileikkauskyselytutkimuksen tulokset. Randomoidussa sarjassa MR-defekografialla todennettiin, että rektopeksialeikkauksen jälkeen peräsuolen sisäinen tuppeuma, rektoseele ja enteroseele korjaantuvat. Rektopeksialeikkaus palauttaa lantion taka- ja keskiosan anatomian, vähentää elinten dynaamista liikkuvuutta ja parantaa lantionpohjan toimintaa sekä oireisiin liittyvää elämänlaatua, erityisesti suolioireiden ja gynekologisten laskeumaoireiden osalta. Robottiavusteinen ja laparoskooppinen tekniikka olivat samanvertaisia perioperatiivisten parametrien, komplikaatioiden, anatomisten ja toiminnallisten tulosten suhteen. Vaikka kustannusvertailussa kalliimpi robottikirurgia voi osoittautua kustannustehokkaaksi pitkäaikaisseurannassa, yhdenvertaiset tulokset eivät oikeuta menetelmää rutiinikäyttöön. Retrospektiivisen tutkimuksen poikkileikkauskyselyn mukaan toiminnalliset tulokset säilyvät pitkäaikaisseurannassa, residiivien (7,1 %) ja komplikaatioiden (10 %) määrä on hyväksyttävä ja verkkoon liittyviä komplikaatioita esiintyy vähän (1,4 %). Leikkauksen jälkeen ilmenee myös uusia oireita, kuten ulostuspakkoa tai virtsankarkailua. Toisaalta virtsankarkailuoire voi korjaantuakin. Pitkäaikaisseurannassa totaalin rektumprolapsin vuoksi leikatut potilaat hyötyvät leikkauksesta enemmän kuin oireisen internin prolapsin vuoksi leikatut. Osa väitöskirjatyön tuloksista tukee moniammatillisen lähestymistavan käyttöä potilaiden arvioinnissa. Jatkossa robottikirurgian käytön indikaatioita rektopeksialeikkauksissa tulisi arvioida isommissa potilasaineistoissa.

Internationally as well as in Sweden, efforts for improvement in gynaecological surgery in recent decades have mainly focused on three new treatment concepts: (1) Use of minimally invasive procedures: since there is an interdependency between the extent of surgical trauma and the risk for adverse outcome, increased use of supposedly atraumatic endoscopic procedures has revolutionized several aspects of surgical care (2) A multimodal approach to eliminate harmful procedures in the peri-operative process based on evidence-based principles (3) Introduction of implants to support damaged tissue with synthetic mesh in incontinence and pelvic organ prolapse patients. Research question 1: Is introduction of a minimally invasive operation enough per se or is the measured improvement mediated by elimination of harmful procedures in the perioperative process? Findings: Our study (Paper I) indicates that by applying a multimodal intervention programme for the pre- and postoperative care of patients undergoing supravaginal hysterectomy, the surgical procedure per se is of less importance than generally considered. Patient-related parameters such as length of postoperative hospital stay, number of days at home with need of painkillers, number of days before return to normal activities, and patient satisfaction did not differ between patients undergoing the laparoscopic procedure and patients undergoing abdominal supravaginal hysterectomy. When evaluating a new and presumably improved operative procedure against an established standard procedure, it is mandatory and of fundamental importance that the two methods are aligned in terms of perioperative care provided. Research question 2: Under which circumstances can it be assumed that a new surgical procedure showing promising efficacy in one setting can be reproduced with similar results in a different clinical setting (Paper I)? Findings: The operating surgeons concluded that, in their hands and under local conditions, laparoscopic technique for supravaginal hysterectomy was not superior to traditional open hysterectomy and stopped using laparoscopic technique. It seems necessary, prior to routine use, to monitor, using scientific tools, whether the advantages described in the literature are achievable under local conditions. Research question 3: Do expected advantages of implants outweigh the unwanted effects and complications caused by implants in operations for recurrent cystocele (Paper II)? Findings: Mesh has better durability but more (minor) complications. It is not possible to determine whether mesh is "generally better" than native tissue operation. Some may focus on the improved durability, others on the increased risks. The surgeon must make a risk assessment for each individual case. The patient must be sufficiently informed to understand the risks and make a personal, informed decision whether she wants an augmentation by implant. Essential for this process is a clear, comprehensible picture of both desired and unwanted effects of the planned surgery. In this context, studies like ours might be of use.

O prolapso uterino tem sua incidência aumentada na pós-menopausa. O objetivo deste estudo é identificar as alterações na matriz extracelular do ligamento cardinal associadas à menopausa e ao prolapso uterino. Ligamento cardinal de três diferentes grupos de mulheres, pré-menopausa, prolapso uterino e pós-menopausa, foram identificados e biopsiados durante 57 histerectomias abdominais ou vaginais. As amostras foram processadas por métodos bioquímicos para caracterização e quantificação de glicosaminoglicanos sulfatados e colágeno. As concentrações relativas de glicosaminoglicanos foram obtidas por eletroforese. Procedimentos histológicos foram feitos para identificar fibras elásticas (Weigert), distribuição de colágeno (Picro Sirius) e decorin (imunohistoquímica). Nossos resultados mostraram aumento na concentração de GAG de 72,2%, redução na concentração de colágeno de 37% e diminuição de 22% de fibras elásticas no grupo de prolapso uterino quando comparado ao grupo da pós-menopausa (p<0,05, p<0,04 e p<0,05 respectivamente). As concentrações relativas de glicosaminoglicanos sulfatados para condroitin sulfato, heparan sulfato e dermatan sulfato não mostraram diferenças entre os três grupos. A organização do colágeno foi similar entre os três grupos e a marcação do decorin pareceu estar diminuída no grupo de prolapso uterino. Nossos resultados indicam alterações no metabolismo do tecido conjuntivo. O ligamento cardinal da mulher na pós-menopausa possui uma matriz extracelular mais densa. Esta alteração não ocorre na mulher com prolapso uterino. / Uterine prolapse has increase of incidence after menopause. The aim of this study was to identify the changes in extracellular matrix of cardinal ligaments associated to menopause and uterine prolapse. Cardinal ligament of 3 different groups (pre-menopause, menopause and uterine prolapse) are identified and biopsied during 57 womens abdominal or vaginal hysterectomy. Biopsy specimens were assessed by biochemical methods to characterize and quantify sulfated glycosaminoglycans and collagen. Relative concentrations of GAG were obtained by electrophoresis. Histological procedures are made to identify elastic fibers (Weigert) collagen distribution (Picro sirius) and decorin (immunohistochemistry). Our results showed increase in GAG concentration 72.2% in uterine prolapse group compared to menopause group (p<0.05). Collagen concentration was 37% lower in uterine prolapse group compared to menopause group (p<0.04). Relative concentration of GAG: heparan sulfate, chondroitin sulfate and dermatan sulfate showed no differences among three groups. Elastic fibers showed a significant reduction of approximately 22% uterine prolapse group compared to menopause group (p<0.05). Collagen organization was similar in three groups and the staining pattern of decorin seemed to be decreased in uterine prolapse group. Our results indicate changes in connective tissue metabolism. Cardinal ligament in postmenopausal women has a denser extracellular matrix. This change is not observed in women with uterine prolapse.

Background: Pelvic organ prolapse (POP) can be treated surgically or, more conservatively, with use of a pessary. Objective: To determine if the population of women treated for POP with the use of a pessary in one Nurse Practitioner's (NP) practice demonstrated health outcomes as better, same, or needing improvement through use of a data-based practice model from encounter data extracted from the electronic health record (EHR).Design: The project design was a quality improvement (QI) project, descriptive in nature. One Plan Do Study Act (PDSA) cycle was conducted for this QI project. Setting: NP managed specialty clinic in urban Southwestern Arizona that provides services to women with POP. Patients: Ten randomly selected women who had been treated conservatively for POP with use of a pessary were identified as two subpopulations and evaluated: women who received professional management of the pessary and women who were patient managed. Intervention: The intervention was the development of a data-based practice model, using patient profile data elements derived from the documented EHR encounters of the 10 women. Measurements: Twelve scales were developed to evaluate the patient profile data elements, generating numeric scores for each encounter. Two Decision Rules were then used to evaluate numeric scores by encounter, creating primary and secondary health outcomes. Limitations: Two limitations were identified. The QI project was limited by the small sample size of 10 patients. This is however, true to PDSA guidelines that recommend small scale cycles. The data were limited as only documented data were used. Conclusions: In general, the expected outcome was the outcome observed; the provider was unaware of any women in this QI Project who were not successfully treated with use of a pessary for treatment of POP. The value of this data-based practice model is that outcomes can be aggregated across populations rather than relying on recall of individual outcomes and therefore has potential to be used regularly and systematically as a quality feedback loop, as well as on a larger scale in future PDSA cycles to determine other outcomes beyond a single provider in this or other similar clinical populations.

Diss. (sammanfattning) Linköping : Univ., 2003. / Härtill 4 uppsatser.

Le prolapsus génital est une pathologie fonctionnelle féminine fréquente dont le retentissement sur la qualité de vie des femmes peut être important et constitue aujourd'hui un véritable enjeu de santé publique. / Genital prolapse is a frequent female functional pathology that can have strong impact on quality of life; it is today a real public health issue. Surgical treatment of the various stages of cystocele is a current challenge. We developed an innovative 3D numerical model using the Finite Elements method, to enable simulation of the various surgical techniques. The model also allowed validation of our surgical hypotheses and provided some answers to outstanding questions in cystocele surgery. The first of my PhD studies allowed me to make a complete review of the anatomical pelvic organ support structures involved in prolapse, and to distinguish certain anatomic theories relating clinical expression to specific anatomic lesions. The various theories are actually quite close and complementary, but differ in terms of the mechanism implicated. The second study involved designing a 3D numerical biomechanical model of the pelvic floor, based on Finite Elements analysis coupled to dynamic MRI. The model allowed me to assess the various theories of pelvic organ suspension, and to design simulations of cystocele mobility. The model provided better understanding of the anatomic structures involved in prolapse. The third study involved designing a 3D numerical pathologic model based on data for patients with grade ≥ 3 cystocele. The model enabled analysis and assessment of the impact of the various surgical correction techniques and fixation zones on organ mobility. Although the results have not been validated clinically, the study contributed to the scientific literature on the importance of mesh reinforcement in the management of cystocele. Comparison between the various techniques (sacrocolpopexy, vaginal mesh suspension, sacrospinous fixation) using the POP-Q points found that point Ba was better corrected by sacrocolpopexy than sacrospinous fixation or vaginal mesh suspension. For sacrospinous fixation, the further it is performed from the sciatic spine, the better the apical correction of point C but the poorer the correction of point Ba. These findings could be used to improve surgical correction techniques and standardize practice. Thus, our 3D numerical cystocele model could contribute to selecting the surgical technique for correction of the cervix and anterior vaginal wall. The Finite Elements model of the pelvic system provides better understanding of the mechanisms underlying surgical correction of cystocele and the vaginal apex. It could also enable the results of prolapse surgery to be predicted, adapting technique to the individual patient by preoperative simulation. Simulation provides original and interesting information on mobility in prolapse. The present simulation results obviously need future assessment in comparison with clinical practice. In conclusion, simulation and the implementation of a 3D numerical model of pelvic mobility now allows better understanding of the mechanisms underlying pelvic statics disorder, with simulation of pathological pelvic mobility and of prolapse surgery procedures.

Made available in DSpace on 2014-06-11T19:31:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-11-13Bitstream added on 2014-06-13T20:01:40Z : No. of bitstreams: 1 cabral_vp_dr_jabo.pdf: 464248 bytes, checksum: 83473e8d960d8d22d0470e9cf4817b9e (MD5) / Cesumar / Com o trabalho, propõe-se apresentar um modelo experimental de prolapso da glândula da terceira pálpebra em cães, valendo-se, para tal, da ressecção do retináculo glandular periorbitário e de estudos macro e microscópicos, bem como das intercorrências clínicas, quanto à produção lacrimal. As variáveis foram estudadas em bulbos dos olhos com glândulas prolapsadas, em outros com glândulas sepultadas cirurgicamente e em bulbo do olhos que passaram por exérese glandular. Mediante análise dos resultados constatou-se que a produção lacrimal diminuiu, comparativamente às glândulas normais não prolapsadas, notadamente naqueles casos em que as glândulas prolapsadas não foram sepultadas. Glândulas prolapsadas apresentaram-se maiores, quanto ao comprimento, à largura e à espessura. Microscopicamente, glândulas prolapsadas não sepultadas cirurgicamente, exibiram alterações inflamatórias glandulares e ductais em maior intensidade. Das glândulas prolapsadas, 84,2% assim permaneceram, permitindo que fossem estudadas quanto às variáveis concebidas. / The work proposes to present an experimental model of prolepsis of the third eyelid gland in dogs, using for such a thing the resection of the periorbital glandular support and macro and rnicroscopic studies, as well as the c1inical intercurrences, related to the lacrimal production. The variables weíe studied in the eyes bulb with prolapsed glands, in others with surgically buried glands and eyes bulb that passed by glandular exerese. Through the results analysis, it was evidenced that the lacrimal production diminished, when compared with the normal ones not prolapsed, mainly in those cases where the prolapsed glands were not buried. Prolapsed glands are presented bigger, in relation to their length, width and thickness. Microscopically, prolapsed glands that were not buried surgically, showed glandular and duct inflammatory changes in higher intensity. Qut of the prolapsed glands, 84.2% remained in the same way, allowing that they were studied in relation to the conceived variables.