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Biomedical subjects

P R Koninckx

Publications and source records attributed to P R Koninckx.

At least 19 recordsLinked to original sources

A comparative 2-year study of the effects of sequential regimens of 1 mg 17beta-estradiol and trimegestone with a regimen containing estradiol valerate and norethisterone on the bleeding profile and endometrial safety in postmenopausal women.

OBJECTIVE: To compare the bleeding profiles and endometrial protection of two sequential regimens of 17beta-estradiol (17beta-E2) and trimegestone (TMG) with a sequential estradiol valerate (E2V)/norethisterone (NET) regimen. STUDY DESIGN: This was a randomized, double-blind, multicenter study conducted in eight countries in healthy, postmenopausal women with an intact uterus. A total of 1218 women were enrolled into the initial 1-year study (13 cycles), and subsequently 531 of these received treatment for a further year (26 cycles). Treatment regimens were 1 mg 17beta-E2 on days 1-14 and 1 mg 17beta-E2/0.125 mg TMG or 1 mg 17beta-E2/0.25 mg TMG on days 15-28, and 1 mg E2V on days 1-16 and 1 mg E2V/1 mg NET on days 17-28. RESULTS: Mean percentage of women reporting onset of withdrawal bleeding episodes during the week following discontinuation of progestogen was higher in the 1 mg 17beta-E2/0.25 mg TMG group than in the other two treatments, showing a more efficient progestogen effect on the endometrium and good predictability of bleeding onset with this treatment. The mean numbers and average lengths of bleeding episodes were similar in the three treatment groups. Overall, the bleeding profile was more favorable with 1 mg 17beta-E2/0.25 mg TMG than with the lower-dose TMG preparation. Both of the TMG regimens demonstrated a good protective effect on endometrial proliferation, with the 0.25 mg TMG dose showing a lower incidence of proliferative endometrium. CONCLUSION: The 1 mg 17beta-E2/0.25 mg TMG regimen showed an adequate protection of the endometrium, with an overall favorable bleeding profile.

Administration, Oral↗

Implementation of an intuitive writing interface and a laparoscopic robot for gynaecological laser assisted surgery.

The research reported in this paper aims at applying the human handwriting skill to improve and facilitate the control of laser-assisted laparoscopic surgery operations performed by gynaecological surgeons. For the purpose, a laparoscopic robot was interfaced with a digitizing tablet. This interface, further called the intuitive writing interface (IWI), directly converts the hand trajectory, handwritten on the tablet, into an input signal to the robot. It replaces the traditional complex manipulations performed by the surgeon during manual laparoscopic surgery by natural handwriting. It provides the surgeon with an intuitive 'what-you-draw-is-what-you-cut' control facility by employing his/her familiar handwriting skills to control the laser ablation process accurately. The system was successfully built and tested in vitro. Performance tests on the robot resulted in tracking errors in the order of 1 mm in the target plane at an ablation speed of 20 mm/s. The high accuracy of the system was successfully demonstrated by cutting characters 4 mm high on an apple. These results indicate that laser ablation performance is upgraded by the IWI to the accuracy levels of human handwriting, which is much higher than can be obtained with manual laser laparoscopy. Safety features include the use of pen contact with the tablet as a safety switch, and back drivability in the robot joints for easy manual positioning and evacuation in case of emergency.

Computer Peripherals↗

Effect of temperature upon adhesion formation in a laparoscopic mouse model.

BACKGROUND: Pneumoperitoneum can be a cofactor in adhesion formation. Pneumoperitoneum with non-humidified gas causes desiccation in the peritoneal cavity which decreases temperature. The effect of desiccation upon adhesion formation is widely accepted. The specific effect of the associated cooling upon adhesion formation remains unexplored, and was addressed specifically in our laparoscopic mouse model. METHODS: Adhesions were induced during laparoscopy and scored after 7 days during laparotomy. Pneumoperitoneum was performed using CO2 or CO2 with oxygen with or without humidification. Animals were placed at different environmental temperatures to modulate body and intraperitoneal temperature. RESULTS: Anaesthesia, environment with a lower temperature and pneumoperitoneum all independently decrease body temperature. A decrease in body temperature decreases adhesion formation (P=0.004). Therefore, at 37 degrees C, pneumoperitoneum-enhanced adhesion formation is more important than at room temperature (P=0.04). As was observed at room temperature, adhesion formation at 37 degrees C increases with the duration (P=0.01) of pneumoperitoneum and decreases with the addition of 3% of oxygen (P=0.03). CONCLUSIONS: Hypothermia reduces pneumoperitoneum-enhanced adhesion formation, which supports hypoxia as a driving mechanism, since hypothermia decreases the toxic effects of hypoxia and of the ischaemia-reperfusion process. These data could open up new possibilities for adhesion prevention in laparoscopic surgery.

Animals↗

Reactive oxygen species and adhesion formation: clinical implications in adhesion prevention.

Postoperative adhesion formation is a major clinical problem. It has been demonstrated that the pneumoperitoneum used during laparoscopy is a cofactor in adhesion formation. Reactive oxygen species (ROS) are produced in a hyperoxic environment and during the ischaemia/reperfusion process. ROS activity is deleterious for cells, which protect themselves by an antioxidant system known as ROS scavengers. ROS activity can increase by up-regulation of ROS themselves or by down-regulation of ROS scavengers. Recent data also point to a role for ROS in adhesion formation since the administration of ROS scavengers decreases adhesion formation in several animal models. ROS activity increases during both laparotomy and laparoscopy. During laparoscopy, the pneumoperitoneum determines ischaemia at the time of insuflation and reperfusion at the time of deflation. During laparotomy, the environment has a 150 mmHg partial pressure of oxygen (pO(2)), which is much higher than the intracellular pO(2) (5-40 mmHg). This can explain the increase in ROS activity. The aim of this debate is to open a discussion about the importance of ROS activity, besides the known players and mechanisms involved, in adhesion formation and in adhesion prevention.

Female↗

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 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's specialised register of trials (searched Feb 2000), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 2, 2000), MEDLINE (1966-July 2001), EMBASE (1980-July 2001), the National Research Register (Issue 1, 2000) 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 had data appropriate for inclusion within the review. These 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: Meta-analysis of the two randomised trials show improvement in infertility associated with endometriosis with laparoscopic surgery. The largest trial (Marcoux 1997) clearly supports this outcome with an increased chance of pregnancy (OR 2.03, 95% CI 1.28 to 3.24) and ongoing pregnancy rate after 20 weeks (OR 1.95, 95% CI 1.18 to 3.22) but the smaller trial (Gruppo Italiano 1999) does not show benefit (pregnancy OR 0.76, 95% CI 0.31 to 1.88; livebirth OR 0.85, 95% CI 0.32 to 2.28). Combining ongoing pregnancy and live birth rates there was a statistically significant increase with surgery (OR 1.64, 95% CI 1.05 to 2.57). REVIEWER'S CONCLUSIONS: The use of laparoscopic surgery in the treatment of minimal and mild endometriosis may improve success rates. The relevant trials have some methodological problems and further research in this area is needed.

Endometriosis↗

Peritoneal mesothelial hypoxia during pneumoperitoneum is a cofactor in adhesion formation in a laparoscopic mouse model.

OBJECTIVE: To develop a laparoscopic mouse model to evaluate the hypothesis that mesothelial hypoxia during pneumoperitoneum is a cofactor in adhesion formation. DESIGN: Prospective randomized trials. SETTING: Academic research center. ANIMAL(S): One hundred thirty female Naval Medical Research Institute (NMRI) mice. INTERVENTION(S): Adhesions were induced by opposing monopolar lesions in uterine horns and pelvic side walls during laparoscopy and evaluated after 7 or 28 days under microscopic vision during laparotomy. The following pneumoperitoneum variables were assessed: duration (10 or 60 minutes), insufflation pressure (5 or 15 cm of water), insufflation gas (CO(2) or helium), and addition of oxygen (0-12%). MAIN OUTCOME MEASURE(S): Adhesions were scored quantitatively and qualitatively for extent, type, and tenacity. RESULT(S): Scoring of adhesions 7 or 28 days after laparoscopic surgery was comparable. Adhesions increased with duration of pneumoperitoneum and with insufflation pressure and decreased with the addition of oxygen. Half-maximal reduction of adhesions was obtained at 1.5% oxygen, whereas a maximal reduction required only 2%-3%. The effect of CO(2) and helium was similar. CONCLUSION(S): These data demonstrate the feasibility of the intubated laparoscopic mouse model and confirm previous observations in rabbits, indicating that mesothelial hypoxia plays a key role in adhesion formation.

Animals↗

Umbilical endometriosis after unprotected removal of uterine pieces through the umbilicus.

We reviewed the frequency of umbilical endometriosis after laparoscopic-assisted subtotal hysterectomy with unprotected removal of uterine segments through the umbilical incision. Retrospective analysis of surgical records was followed by recall and clinical examination of 10 patients. Two women developed umbilical endometriosis. One was the only patient operated during menstruation. The other was one of two women operated in the late luteal phase and with subsequent adequate exposure to endogenous or exogenous estrogens. From 1976-1997, 22 reports of umbilical endometriosis were published: 18 cases were spontaneous, 2 occurred after ring sterilization, and 2 after diagnostic laparoscopy. These data lend support to the concept that implantation and the potential development of menstrual endometrium are increased after surgery. It is speculated that procedures that expose menstrual endometrial cells to nonepithelialized areas could be associated with an increased risk of endometriosis.

Adult↗

Adhesion formation in intubated rabbits increases with high insufflation pressure during endoscopic surgery.

The aim of the study was to test the hypothesis that the increase in adhesion formation by CO(2) pneumoperitoneum is caused by mesothelial hypoxaemia. Therefore the effect of the intra-abdominal pressure together with the flow rate upon adhesion formation was evaluated in rabbits following laser and bipolar lesions during endoscopic surgery using humidified CO(2) at 35 +/- 1 degrees C. The intra-abdominal pressure and flow rate were 5 mmHg and 1 l/min in group 1 (n = 5), 5 mmHg and 10 l/min in group 2 (n = 4), 20 mmHg and 1 l/min in group 3 (n = 5) and 20 mmHg and 10 l/min in group 4 (n = 4) respectively. A rapid and reliable intubation method for rabbits was developed to permit high insufflation pressure. By two-way analysis of variance, total adhesion scores following a laser lesion increased with flow rate (P = 0.0003) and insufflation pressure (P = 0.002). Total adhesion scores of bipolar lesions increased with pressure (P = 0.02) but not with flow rate (P = 0.1). The total adhesion scores of laser and bipolar lesions together increased with flow rate (P = 0.005) and with insufflation pressure (P = 0.004). There was no statistical interaction between flow rate and insufflation pressure. In conclusion, the insufflation pressure in endoscopic surgery with CO(2) pneumoperitoneum is a co-factor in adhesion formation, together with desiccation.

Analysis of Variance↗

Hypoxaemia induced by CO(2) or helium pneumoperitoneum is a co-factor in adhesion formation in rabbits.

A prospective randomized trial in a rabbit model was performed to test the hypothesis that the increase in adhesion formation following prolonged pneumoperitoneum is mediated by peritoneal hypoxaemia. Laparoscopic standardized opposing lesions were performed in uterine horns and pelvic sidewalls by bipolar coagulation and CO(2) laser in six groups of eight animals. Pure CO(2) or helium pneumoperitoneum was used for 10 (groups I and IV) or 45 min (groups II and V) to confirm the effect of duration of pneumoperitoneum and 96% of CO(2) or helium with 4% of oxygen (group III and VI) for 45 min to assess the effect of the addition of oxygen. After 7 days, adhesion formation was scored by laparoscopy. By two-way analysis of variance, total, extent, type and tenacity of adhesion scores increased (P = 0.0003, P = 0.0004, P = 0.0004 and P = 0.004) with increasing duration of pneumoperitoneum and decreased (P = 0.02, P = 0.03, P = 0.01 and P = 0.05) with the addition of oxygen. No differences were found between CO(2) and helium. In conclusion these data confirm the effect of pneumoperitoneum upon adhesions and demonstrate its reduction by oxygen, strongly suggesting that the main cause of adhesion formation is the relatively superficial hypoxaemia produced by the pneumoperitoneum.

Acidosis↗

Correlation between endometriosis and pelvic pain.

STUDY OBJECTIVE: To evaluate the relationship between prevalence and severity of chronic pelvic pain (CPP) and stage, site, and type of endometriosis. DESIGN: Prospective, observational study (Canadian Task Force classification II-2). SETTING: University Hospital. PATIENTS: Of 90 consecutive women with biopsy-proved endometriosis, laparoscopy was performed in 69 for pelvic pain and in 21 for infertility or clinical and ultrasonographic suspicion of ovarian endometriosis. INTERVENTION: Preoperatively, using a 10-point visual analog scale, the severity of dysmenorrhea, CPP, and deep dyspareunia was assessed. During laparoscopy all visible endometriotic lesions were recorded and treated. MEASUREMENTS AND MAIN RESULTS: Ten women (11.1%) had no pain; 72 had dysmenorrhea (mild in 13, moderate in 37, severe in 22); 55 had CPP (mild in 11, moderate in 25, severe in 19); and 39 deep dyspareunia (mild in 5, moderate in 31, severe in 3). The severity of dysmenorrhea significantly correlated with the presence and extent of pelvic adhesions (p = 0.004); the severity of CPP correlated with deep endometriosis on the uterosacral ligaments (p = 0.0001) and extent of pelvic adhesions (p = 0.02); and deep dyspareunia correlated with deep endometriosis on the uterosacral ligaments (p = 0.04). Total pain score significantly correlated with deep endometriosis on the uterosacral ligaments (p = 0.0001), peritoneal adhesions (p = 0.01), and extent of adnexal adhesions (p = 0.01). No significant correlation was found among revised American Fertility Society stage of endometriosis; presence and size of ovarian endometriomas; extent, type, and site of peritoneal lesions; and pain scores. By logistic regression analysis, the presence and intensity of total pain could be predicted simultaneously by the presence of deep endometriosis (p = 0.0001) and presence and extent of adnexal adhesions without cystic endometriosis (p = 0.01), and by the presence of ovarian endometrioma with periovarian adhesions (p = 0.03). Chronic pelvic pain was predicted by both deep endometriosis (p = 0.0001) and ovarian endometriomas with adnexal adhesions (p = 0.03). Deep dyspareunia was predicted simultaneously by deep endometriosis (p = 0.01) and an ovarian endometrioma with periovarian adhesions (p = 0. 008). Conclusion. Deep endometriosis, pelvic adhesions, and ovarian cystic endometriosis were independent predictors of pelvic pain. These data strongly suggest that it is not the size of ovarian cystic endometriosis but the association with adhesions that causes pelvic pain.

Adolescent↗

Effect of the diameter of the endoscope and of surgeon training on the duration and quality of laparoscopic surgery in a rabbit model.

STUDY OBJECTIVE: To evaluate the effect of diameter of the endoscope on the duration and quality of laparoscopic surgery. DESIGN: Prospective, randomized trial (Canadian Task Force classification I). SETTING: Centre for Surgical Technologies. SUBJECTS: Sixty adult, female, New Zealand, white rabbits. INTERVENTION: Two series of laparoscopic nephrectomies, one each performed by an experienced and an inexperienced surgeon comparing 10-, 5-, 4-, and 2-mm endoscopes. MEASUREMENTS AND MAIN RESULTS: Besides duration of surgery and occurrence of bleeding, the quality of dissection was scored by adding scores of dissection of renal vessels, ureters, and kidneys. During consecutive nephrectomies, the duration of surgery (p = 0. 001) and occurrence of bleeding (p = 0.02) decreased, whereas the quality of dissection increased (p = 0.002), demonstrating the learning curve, mainly for the less experienced surgeon. Duration of surgery (p = 0.04) decreased and quality of dissection increased (p = 0.05) when the larger endoscope was used. This was the case only for the less experienced surgeon, whereas for the experienced surgeon it had only a slight effect on learning curve. CONCLUSION: These results confirm a learning curve of nephrectomy consisting of some 20 animals. In addition, the endoscope diameter and thus quality of image affect both duration and quality of surgery, especially for less experienced surgeons.

Animals↗

The mouse as a model to study adhesion formation following endoscopic surgery: a preliminary report.

Our aim was to investigate the feasibility of a mouse model to study adhesion formation following endoscopic surgery. Following preliminary studies to establish anaesthesia and pneumoperitoneum pressure, a prospective randomized study was carried out to investigate the effect of CO2 pneumoperitoneum on postoperative adhesions. In group I (control group), the duration of pneumoperitoneum was shorter than 5 min. In groups II, III and IV, pneumoperitoneum was maintained for 60 min without flow, with a continuous low flow (1 ml/min) and a continuous high flow (10 ml/min) through the abdominal cavities of the mice using non-humidified CO2, respectively. Adhesions were scored after 7 days by laparotomy. The total adhesion scores were 0.9 +/- 0.8 (n = 15) in control group, 2.4 +/- 0.8 (n = 15) (P < 0.001 versus control group) in group II with no flow, 2.6 +/- 1.3 (n = 15) (P < 0.001 versus control group) in group III with a continuous low flow and 4.3 +/- 0.9 (n = 15) (P < 0.001 versus control group and P < 0.001 versus group II and III) in group IV with a continuous high flow. In conclusion, the mouse can be used as a model to study adhesion formation following endoscopic surgery. Duration of CO2 pneumoperitoneum is a co-factor in adhesion formation.

Animals↗

The influence of in-vitro culture versus stimulated and untreated oviductal environment on mouse embryo development and implantation.

A prospective randomised study was performed to evaluate stimulated versus natural oviductal environment in comparison with in-vitro culture for the developmental capacity of mouse embryos. Therefore, embryos of superovulated F1 hybrid CBAxC57Bl females were collected at 17, 22, 41 and 46 h after human chorionic gonadotrophin treatment and randomly divided into five groups. They were either transferred immediately to untreated pseudopregnant females, cultured in vitro for 5, 24 or 29 h before transfer, or cultured in vitro for 96 h to blastocysts. The transfers resulted in an impaired implantation (P < 0.001) and a lower numbers of living fetuses (P < 0.001) when embryos had been exposed longer to the stimulated oviductal environment. Similar results were obtained after a longer period of in-vitro culture (P < 0.05). However when embryos were flushed earlier from the superovulated mice and cultured longer in-vitro until the transfer was performed, the implantation rate was improved (P < 0.01). Blastocyst development, however, was better (P < 0.001) when embryos were flushed later. In conclusion, the stimulated oviductal environment impairs the developmental capacity of embryos in comparison with untreated pseudopregnant females. In-vitro culture is also suboptimal but better than the stimulated oviductal environment.

Animals↗

Implantation versus infiltration: the Sampson versus the endometriotic disease theory.

It has been assumed that endometriosis is a progressive disease, with growth and development of lesions being inevitable once the disease has started. The implantation and the metaplasia theories describe the mechanism of initiation of endometriotic lesions, but do not explain the different clinical manifestations of endometriosis. To explain the variable expression, growth and development of lesions into severe disease, a new endometriotic disease theory is proposed. This theory suggests that progression of endometriosis to endometriotic disease is considered similar to the onset and progression of a benign tumour. In this theory, the most important factor in the development of endometriotic disease is not the initial implantation/metaplasia, but cellular changes such as mutations. According to this theory, endometriotic disease develops from endometriotic cells that have 'escaped' the influence of protective and regulatory factors in the peritoneal fluid.

Animals↗

Pathogenesis of endometriosis: the role of peritoneal fluid.

Peritoneal fluid is a specific microenvironment. It originates mainly as an ovarian exudation product due to increased vascular permeability, and contains large amounts of macrophages and their secretion products, which include growth factors, cytokines and angiogenic factors. Similarly, within the ovary, there is also a specific microenvironment, best characterised by the follicular milieu with steroid hormone concentrations that are 1,000 times higher than in plasma. Since endometrial cells in peritoneal fluid and superficially implanted cells will be influenced by peritoneal fluid concentrations, any differences found between minimal endometriosis and eutopic endometrium could be the consequence of their different local environments, rather than inherent cellular differences. Superficial endometrial implants may be regulated by factors in peritoneal fluid, while deep endometriosis and cystic ovarian endometriosis may be under the influence of factors in blood and within the ovary, in which case minimal endometriosis may be physiologic only, while deep endometriosis and cystic ovarian endometriosis, both associated with pelvic pain and infertility, may be a pathological state. In conclusion, the local endocrine environment, that is, in blood, peritoneal fluid, and within the ovary, should be taken into account to explain the differences between superficial, deep and cystic ovarian endometriosis, together with inherent differences in the endometrial cells of women with and without endometriosis.

Animals↗

The physiopathology of endometriosis: pollution and dioxin.

Reports in the literature of an increasing incidence of endometriosis in industrialized countries and increasing problems with pollution in these countries leads to speculation about a possible link between one of the most harmful components of pollution, dioxin, and endometriosis. To establish this link, we need to examine three issues more closely: What are the effects of dioxin, what is the true incidence of endometriosis, and what is the nature of the association between endometriosis and dioxin. This report reviews current thinking on these issues.

Animals↗