Objectives: The aim of this dissertation was to examine bias in randomized controlled trials (RCTs) and non-randomized studies (NRS) in surgery using the literature evaluating laparoscopy and conventional (i.e. open) surgery for the treatment of colon cancer as a case study. The objectives were 1) to develop a conceptual framework for bias in comparative NRS; 2) to compare effect estimates from NRS with those from RCTs at low risk of bias; 3) to explore the impact of NRS-design attributes on estimates of treatment effect. Methods: The methods included a modified framework synthesis, systematic review of the literature, random-effects meta-analyses, and frequentist and Bayesian meta-regression. The Cochrane Risk of Bias Tool was used to classify trials as Strong RCTs (i.e. low risk of bias) or Typical RCTs (i.e. unclear or high risk of bias). Results: A conceptual framework for bias in comparative NRS was developed and it contains 37 individual sources of bias or “items”. These items were organized within 6 overarching “domains”: selection bias, information bias, performance bias, detection bias, attrition bias, and selective reporting bias. Our analyses revealed that NRS were associated with more extreme estimates of benefit for laparoscopy than Strong RCTs when examining subjective outcomes. The odds ratios from NRS were 36% smaller (i.e. demonstrating more benefit for laparoscopy) than those from Strong RCTs for the outcome post-operative complications (Ratio of Odds Ratios, ROR 0.64, [0.42, 0.97], p=0.04). Similar exaggerated benefit was seen among NRS when assessing length of stay, (Difference in Mean Differences, -2.15 days, [-4.08, -0.21], p=0.03). This pattern was not observed with the objective outcomes peri-operative mortality and number of lymph nodes harvested. Analyses adjusted for period effects and between-study case-mix yielded similar findings. Finally, effect estimates in NRS did not consistently vary according to the presence or absence of nine design characteristics identified from the conceptual framework. Conclusions: We have demonstrated that the results of surgical NRS can be significantly biased as compared with those of low risk of bias RCTs when evaluating subjective outcomes. However, none of the nine NRS-design characteristics examined was consistently associated with biased effect estimates.

Objectives: The aim of this dissertation was to examine bias in randomized controlled trials (RCTs) and non-randomized studies (NRS) in surgery using the literature evaluating laparoscopy and conventional (i.e. open) surgery for the treatment of colon cancer as a case study. The objectives were 1) to develop a conceptual framework for bias in comparative NRS; 2) to compare effect estimates from NRS with those from RCTs at low risk of bias; 3) to explore the impact of NRS-design attributes on estimates of treatment effect. Methods: The methods included a modified framework synthesis, systematic review of the literature, random-effects meta-analyses, and frequentist and Bayesian meta-regression. The Cochrane Risk of Bias Tool was used to classify trials as Strong RCTs (i.e. low risk of bias) or Typical RCTs (i.e. unclear or high risk of bias). Results: A conceptual framework for bias in comparative NRS was developed and it contains 37 individual sources of bias or “items”. These items were organized within 6 overarching “domains”: selection bias, information bias, performance bias, detection bias, attrition bias, and selective reporting bias. Our analyses revealed that NRS were associated with more extreme estimates of benefit for laparoscopy than Strong RCTs when examining subjective outcomes. The odds ratios from NRS were 36% smaller (i.e. demonstrating more benefit for laparoscopy) than those from Strong RCTs for the outcome post-operative complications (Ratio of Odds Ratios, ROR 0.64, [0.42, 0.97], p=0.04). Similar exaggerated benefit was seen among NRS when assessing length of stay, (Difference in Mean Differences, -2.15 days, [-4.08, -0.21], p=0.03). This pattern was not observed with the objective outcomes peri-operative mortality and number of lymph nodes harvested. Analyses adjusted for period effects and between-study case-mix yielded similar findings. Finally, effect estimates in NRS did not consistently vary according to the presence or absence of nine design characteristics identified from the conceptual framework. Conclusions: We have demonstrated that the results of surgical NRS can be significantly biased as compared with those of low risk of bias RCTs when evaluating subjective outcomes. However, none of the nine NRS-design characteristics examined was consistently associated with biased effect estimates.

Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, Kadın Hastalıkları ve Doğum Anabilim Dalı, 2006. / Bibliyografya var.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Diss. (sammanfattning) Linköping : Univ., 2003. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 4 uppsatser.

Laparoscopic surgery or minimally invasive surgery has great advantages compared with the conventional open surgery, such as reduced pain, shorter recovery time and lower infection rate. It has become a standard clinical procedure for cholecystectomy, appendectomy and splenectomy. The state-of-the-art laparoscopic technologies suffer from several significant limitations, one of which is the tradeoff of the limited instantaneous field of view (FOV) for high spatial resolution versus the wide FOV for situational awareness but with diminished spatial resolution. Standard laparoscopes lack the ability to acquire both wide-angle and high-resolution images simultaneously through a single scope. During the surgery, a trained assistant is required to manipulate the laparoscope. The practice of frequently maneuvering the laparoscope by a trained assistant can lead to poor or awkward ergonomic scenarios. This type of ergonomic conflicts imposes inherent challenges to laparoscopic procedures, and it is further aggravated with the introduction of single port access (SPA) techniques to laparoscopic surgery. SPA uses one combined surgical port for all instruments instead of using multiple ports in the abdominal wall. The grouping of ports raises a number of challenges, including the tunnel vision due to the in-line arrangement of instruments, poor triangulation of instruments, and the instrument collision due to the close proximity to other surgical devices. A multi-resolution foveated laparoscope (MRFL) was proposed to address those limitations of the current laparoscopic surgery. The MRFL is able to simultaneously capture a wide-angle view for situational awareness and a high-resolution zoomed-in view for fine details. The high-resolution view can be scanned and registered anywhere within the wide-angle view, enabled by a 2D optical scanning mechanism. In addition, the high-resolution probe has optical zoom and autofocus capabilities, so that the field coverage can be dynamically varied while keep the same focus distance as the wide-angle probe. Moreover, the MRFL has a large working distance compared with the standard laparoscopes, the wide-angle probe has more than 8x field coverage than a standard laparoscope. On the other hand, the high-resolution probe has 3x spatial resolution than a standard one. These versatile capabilities are anticipated to have significant impacts on the diagnostic, clinical and technical aspects of minimally invasive surgery. In this dissertation, the development of the multi-resolution foveated laparoscope was discussed in detail. Starting from the refinement of the 1st order specifications, system configurations, and initial prototype demonstration, a customized dual-view MRFL system with fixed optical magnifications was developed and demonstrated. After the in-vivo test of the first generation prototype of the MRFL, further improvement was made on the high-resolution probe by adding an optical zoom and auto-focusing capability. The optical design, implementation and experimental validation of the MRFL prototypes were presented and discussed in detail.

Orientador: Wilter Ricardo Russiano Vicente / Banca: Luiz Fernando de Souza Rodrigues / Banca: César Roberto Esper / Resumo: Avaliou-se macro e microscopicamente os ovários de ovelhas submetidas a sucessivas aspirações foliculares, com o objetivo de se verificar se houve ou não interferência na produção oocitária e morfologia das gônadas; além da avaliação macroscópica do trato genital interno. Dezoito ovelhas da raça Santa Inês, distribuídas aleatoriamente compuseram três grupos experimentais de igual número (n=6). G0, G1, G9 com 0, 1 e 9 repetições, respectivamente. A sincronização do estro foi feita utilizando-se protocolo curto com MAP, seguindo-se estimulação, em dose única, com 80mg de FSHp e 300 UI de eCG (IM) e após 36 horas realizavam-se as aspirações foliculares por vídeolaparoscopia, com intervalo de 7 dias. Os folículos visibilizados, os aspirados e os oócitos recuperados foram contabilizados. Após a última intervenção foi realizada ovariectomia para avaliar os macro e microscopicamente, a existência ou não de lesões causadas pelas punções foliculares, classificando a intensidade do processo em ausente (0), leve (1), moderada (2) e severa (3). Os dados foram expressos em média e desvio padrão, comparados pelo teste one-way ANOVA e teste de Tukey. Os números de folículos visibilizados, aspirados e oócitos recuperados foram de 13,24±2,0, 11,27±3,03 e 5,79±2,3 respectivamente, com taxa de recuperação de 51,69%, não havendo diferenças entre as nove sessões (p>0,05). Também não se verificou, macroscopicamnte, lesões no trato genital interno, nem alterações consideráveis nas análises histológicas, sendo o escore 0±0 para o G0, 0,1±0,4 para o G1 e 0±0 para o G9 (p>0,05). Conclui-se que as nove sessões de superovulação e aspiração folicular não causam lesões ovarianas e não interferiram na produção de folículos em ovelhas da raça Santa Inês / Abstract: We evaluated macroscopically and microscopically the ovaries of ewes to repeated follicular aspiration, in order to verify whether or not there was interference with the production oocyte and gonad morphology, besides the macroscopic evaluation of internal genital tract. Eighteen sheep Santa Ines, randomly distributed three groups composed of equal numbers (n = 6). G0, G1, G9 with 0, 1 and 9 replicates, respectively. Synchronization of estrus was performed using short protocol with MAP, followed by stimulation in a single dose of 80mg FSHp and 300 IU of eCG (IM) and after 36 hours was held at the follicular aspiration by laparoscopy with interval 7 days. The follicles visualized, aspirated and the oocytes recovered were counted. After the last intervention was performed ovariectomy was performed to assess the macro and microscopically, the presence or absence of lesions caused by follicular puncture, classifying the intensity of the process as absent (0), mild (1), moderate (2) and severe (3) . Data were expressed as mean and standard deviation and compared by using one-way ANOVA and Tukey test. The numbers of follicles visualized, aspirated and oocytes recovered were 13.24 ± 2.0, 11.27 ± 3.03 and 5.79 ± 2.3 respectively, with a recovery rate of 51.69%, with no differences among the nine sessions (p> 0.05). Nor is there, macroscopicamnte, internal genital tract injury, or significant changes in histological evaluations, with a score of 0 ± 0 for G0, 0.1 ± 0.4 for G1 and 0 ± 0 for the G9 (p> 0.05). We conclude the nine sessions of superovulation and ovum do not cause ovarian lesions and did not interfere in the production of follicles in Santa Ines sheep / Mestre

Neste trabalho foi realizado um estudo comparativo entre duas técnicas de oclusão do Complexo Artério Venoso Ovariano (CAVO), por meio da eletrocoagulação monopolar e bipolar, na ovariosalpingohisterectomia (OSH) de felinos hígidos, realizada a partir da técnica com dois portais na linha média ventral. A OSH é um dos procedimentos laparoscópicos mais realizados na casuística da Medicina Veterinária. Diferentes técnicas tem sido realizadas para a execução deste procedimento, dentre as variações incluem-se o número e a disposição dos trocartes, sendo recente a execução da técnica com dois portais. Os objetivos da pesquisa foram descrever a técnica da OSH em felinos com dois portais, bem como comparar a eficácia da eletrocoagulação monopolar e bipolar na obliteração do CAVO. Foram utilizadas 16 gatas adultas, distribuídas aleatoriamente em dois grupos de oito animais. Os procedimentos videocirúrgicos foram realizados por meio da inserção dos portais na linha média ventral nas regiões umbilical e pré-púbica, com os felinos posicionados em decúbito dorsal. Além da verificação da viabilidade da técnica com o uso de apenas dois portais lineares, foram avaliados e comparados o tempo cirúrgico, a eficácia dos dois métodos de eletrocoagulação, a temperatura corpórea pós-operatória, o débito urinário, a formação de enfisema subcutâneo e volume de CO2. Não houve diferença estatística significativa entre o uso da eletrocoagulação mono e bipolar, utilizados na técnica referida acima, embora clinicamente dois animais tenham apresentado lesões cutâneas após o uso da eletrocoagulação monopolar. Conclui-se que os dois métodos de eletrocoagulação utilizados para oclusão dos vasos ovarianos, através da técnica vídeo laparoscópica com dois portais em felinos, são viáveis, rápidos e efetivos em gatas, porém, a energia bipolar mostrou-se um método mais seguro do que a energia monopolar, devido a complicações por queimaduras cutâneas no período pósoperatório. / In this paper, a comparative study was made between two techniques of occlusion of the ovarian arterial-venous complex (OVAC) through monopolar and bipolar electrocoagulation in ovariosalpingohysterectomy (OSH) of healthy cats, carried out from the technique with two linear portals in the ventral midline. The OSH is one of the most commonly performed laparoscopic procedures in casuistry of Veterinary Medicine. Different techniques have been carried out to implement this procedure, among the variations of this technique include the number and arrangement of the trocars, considering recent the implementation of the technique with the use of two portals. The research aims were to describe the technique of ovariohysterectomy in cats with two portals, and the comparison of the effectiveness of monopolar and bipolar electrocoagulation in obliterating of OVAC. Sixteen adult cats were used, divided randomly into two groups of eight animals. The laparoscopic procedures were performed through the insertion of the portals in the ventral midline of abdomen in the umbilical and prepubic regions, with cats under dorsal recumbence position. Besides the verification of the viability of the laparoscopic hybrid technique, using only two linear portals, the surgical time, the effectiveness of the two methods of electrocoagulation, the postoperative body temperature, urine output, the formation of subcutaneous emphysema and CO2 volume were evaluated and compared. There was no statistical significant difference between the use of mono and bipolar electrocoagulation, used in the technique mentioned above, although two animals showed clinical skin lesions after the use of monopolar electrocoagulation. We conclude that the two electrocoagulation methods used for occlusion of the ovarian vessels, through video-laparoscopic with two portals technique in cats, are viable, fast and effective in female cats, however, the bipolar energy proved to be a safer method than the monopolar energy, due to complications from skin burns in the postoperative period.