Anastasia Ussia

Objectives: The aim of this study was to review the importance of peritoneal fluid steroid hormone concentrations to understand the mechanism of hormonal medical treatment of endometriosis-associated pain. Design: The study included a PubMed search and a pilot trial in 8 adolescents. Results: Oral contraceptives (OCs) were designed to inhibit ovulation in all women, and doses are much higher than the mean ovulation-inhibiting dose. Therefore, in most women, half a dose and in some women, even less is sufficient to inhibit ovulation. The inhibition of ovarian function and ovulation decreases estrogen and progesterone concentrations in plasma and peritoneal fluid. Surprisingly, the effect on peritoneal fluid steroid hormone concentrations has not been considered to explain the impact on endometriosis-associated pain. The lowering of the high estrogen concentrations in peritoneal fluid is sufficient to explain the pain decrease in superficial and ovarian endometriosis. A direct progesterone effect is unlikely, given the high progesterone concentrations in the peritoneal fluid of ovulatory women. In 8 adolescents, half an OC dose resulted in an apparently similar pain relief as a full dose (personal observation). Conclusions: The decrease in ovarian and superficial pelvic endometriosis-associated pain with OCs can be explained by lowering the intra-ovarian and the high estrogen concentrations in peritoneal fluid after ovulation. A direct progesterone effect is unlikely. Since OCs are severely overdosed in most women, half a dose is sufficient in most with fewer side effects, permitting individualization of therapy in women not requiring contraception. Understanding peritoneal fluid also explains that hormone replacement therapy is not contraindicated in most women with a history of endometriosis. Since the mechanisms of medical therapy of endometriosis-associated pain and the prevention of progression might be different, the growth of lesions must be monitored during treatment.

Background/Objectives: The diagnosis and treatment of endometriosis should be based on the best available evidence. Emphasising the risk of bias, the pyramid of evidence has the double-blind, randomised controlled trial and its meta-analyses on top. After the grading of all evidence by a group of experts, clinical guidelines are formulated using well-defined rules. Unfortunately, the impact of evidence-based medicine (EBM) on the management of endometriosis has been limited and, possibly, occasionally harmful. Methods: For this research, the inherent problems of diagnosis and treatment were discussed by a working group of endometriosis and EBM specialists, and the relevant literature was reviewed. Results: Most clinical decisions are multivariable, but randomized controlled trials (RCTs) cannot handle multivariability because adopting a factorial design would require prohibitively large cohorts and create randomization problems. Single-factor RCTs represent a simplification of the clinical reality. Heuristics and intuition are both important for training and decision-making in surgery; experience, Bayesian thinking, and learning from the past are seldom considered. Black swan events or severe complications and accidents are marginally discussed in EBM since trial evidence is limited for rare medical events. Conclusions: The limitations of EBM for managing endometriosis and the complementarity of multivariability, heuristics, Bayesian thinking, and experience should be recognized. Especially in surgery, the value of training and heuristics, as well as the importance of documenting the collective experience and of the prevention of complications, are fundamental. These additions to EBM and guidelines will be useful in changing the Wild West mentality of surgery resulting from the limited scope of EBM data because of the inherent multivariability, combined with the low number of similar interventions.

Peritoneal fluid is an ovarian exudate from the growing follicle or corpus luteum. Therefore, the free concentrations of estrogens and progesterone are always much higher than in plasma, especially after ovulation. The peritoneum is not vascularised, and peritoneal implants and the superficial portion of deep endometriosis are likely influenced mainly by peritoneal fluid. Follicular phase progesterone concentrations are as high as during the luteal phase in plasma. This explains that most peritoneal implants are rarely proliferative and out of phase with the endometrium. From some 5 mm of depth onwards, endometriosis is rather influenced by plasma hormone concentra-tions, and the deeper parts can be proliferative as the endometrium. Because of these progesterone concentrations, progesterone resistance has to be postulated, permitting endometriosis lesions to initiate and develop. This opens the discussion of whether endometriosis is similar to the basal endometrium. These peritoneal fluid concentrations are important to understand the natural history and medical therapy of endometriosis. Most medical therapies decrease ovarian function and affect peritoneal fluid steroid hormone concentrations. It is suggested that the efficacy of medical therapy for endometriosis-associated pain is a consequence of the decreased estrogen concentrations in the peritoneal cavity and that the local effect of progestins may not be determinant for pain relief. If this is true, a history of endometriosis should not be considered a contraindication for hormone re-placement therapy.

The relationship between tissue effects, intensity (I), and voltage (V) of a high-frequency alternative current seems well known. However, the translation of the settings of the electrosurgical unit and their use during surgery seems not to be unanimously understood by all surgeons. This results in many variations of surgical technique and plenty of specific questions asked during live surgery. Above 200 V, the heat of the sparks results in the explosion of superficial cells and a cutting effect. With higher voltages, the associated coagulation is increasing. Voltage and amount of energy (Watt=I*V) are independent since a similar amount of energy can be obtained with a continuous current or an intermittent current half the time and a double voltage. Below 200 V, tissue is heated until the steam from boiling tissue stops the current. Therefore, slower heating with less energy or a larger contact area permits deeper coagulation. The maximal output (W) of the electrosurgical unit results in versatility of use besides being a safety measure. The current intensity increases with the area of contact. Therefore, when I*V exceeds the preset output, V has to drop. A limited maximal output thus permits using the same instrument for non-contact cutting with >200V and sparks and coagulation when the contact area is much larger. In conclusion, the tissue effects of electrosurgery vary with the device’s voltage setting (often indicated as force) and the maximal output. The sur-geon’s choice to cut or coagulate by changing the contact area adds versatility.

The loop and knot securities of two polyfilament and two monofilament sutures of four diameters (3.0, 2.0, 0, 1) were evaluated with a tensiometer for four four-throw knots, known to be secure with a 2.0 polyfilament suture. Loop security of Monocryl 1 is low, being 14.7 ± 3.0 Newton (N) for a three-throw half-knot (H3) and 15.4 ± 2.4 N and 28.3 ± 10 N for two (SSs) and four (SSsSsSs) symmetrical sliding half-hitches. This is lower than 18, 24, and 46 N for similar knots with Vicryl. Polyfilament sutures have excellent knot security for all four diameters. Occasionally, some slide open with slightly lower knot security, especially for larger diameters, although this is not clinically problematic. Knot security of monofilament sutures was unpredictable for all four knots, especially for larger diameters, resulting in many clinically insecure knots. A secure monofilament knot requires a six-throw knot with two symmetrical sliding half-hitches or two symmetrical half-knots secured with four asymmetric blocking half-hitches. In conclusion, with polyfilament sutures, four- or five-throw half-knot or half-hitch sequences result in secure knots. For monofilament sutures, loop and knot security is much less, half-knot combinations should be avoided, and secure knots require six-throw knots with four asymmetric blocking half-hitches.

Surgical knots are sequences of half-knots (H) or half-hitches (S), defined by their number of throws, by an opposite or similar rotation compared with the previous one, and for half-hitches whether they are sliding (s) or blocking (b). Opposite rotation results in (more secure) symmetric (s) knots, similar rotation in asymmetric (a) knots, and changing the active and passive ends has the same effect as changing the rotation. Loop security is the force to keep tissue together after a first half-knot or sliding half-hitches. With polyfilament sutures, H2, H3, SSs, and SSsSsSs have a loop security of 10, 18, 28, and 48 Newton (N), respectively. With monofilament sutures, they are only 7, 16, 18, and 25 N. Since many knots can reorganize, the definition of knot security as the force at which the knot opens or the suture breaks should be replaced by the clinically more relevant percentage of clinically dangerous and insecure knots. Secure knots with polyfilament sutures require a minimum of four or five throws, but the risk of destabilization is high. With monofilament sutures, only two symmetric+4 asymmetric blocking half-hitches are secure. In conclusion, in gynecology and in open and laparoscopic surgery, half-hitch sequences are recommended because they are mandatory for monofilament sutures, adding flexibility for loop security with less risk of destabilization.

The loop and knot securities of 2 braided and 2 monofilament sutures of four diameters (3.0, 2.0, 0, 1) were evaluated with a tensiometer for four 4-throw knots known to be secure with a 2.0 polyfilament suture. Loop security of monocryl 1 is low, being 14.7 + 3.0 Newton (N) for a 3-throw half-knot (H3) and 15.4 + 2.4 N and 28.3+ 10 N for 2 (SSs) and 4-throw (SSsSsSs) symmetrical sliding half-hitches. This is lower than 18, 24, and 46 N for similar knots with vicryl. Polyfilament sutures have excellent knot security for all diameters. Occasionally, some slide to open with slightly lower knot security, especially for larger diameters, although not clinically problematic. Knot se-curity of monofilament sutures was unpredictable for all 4 knots, especially for larger diameters, resulting in many clinically insecure knots. A secure monofilament knot requires a 6-throw knot with 2 symmetrical sliding half-hitches or 2 symmetrical half-knots secured with 4 asymmetric blocking half-hitches. In conclusion, with polyfilament sutures, 4 or 5-throw half-knot or half-hitch sequences result in secure knots. For monofilament sutures, loop and knot security is much less, half-knot combinations should be avoided, and secure knots require 6-throw knots with 4 asym-metric half hitches. This conclusion is valid for gynecologic laparoscopic and open surgery, and for surgery in general.

Surgical knots are sequences of half-knots (H) or half-hitches (S), defined by their number of throws, by an opposite or similar rotation compared with the previous one and for half-hitches, whether sliding (s) or blocking (b). Opposite rotation results in (more secure) symmetric (s) knots, similar rotation in asymmetric (a) knots, and changing active and passive ends has the same effect as changing rotation. Loop security is the force to keep tissue together after a first half-knot or sliding half-hitches. With polyfilament sutures H2, H3, SSs and SSsSsSs have a loop security of 10, 18, 28 and 48 Newton (N), respectively. With monofilament sutures, they are only 7, 16, 18 and 25N. Since many knots can reorganise, the definition of knot security as the force at which the knot opens or the suture breaks should be replaced by the clinically more relevant percentage of clinically dangerous and insecure knots. Secure knots with polyfilament sutures require a minimum of 4 or 5 throws, but the risk of destabilisation is high. With monofilament sutures, only 2 symmetric+4 asymmetric blocking half-hitches are secure. In conclusion, half-hitch sequences are recommended since mandatory for monofilament sutures, adding flexibility for loop security with less risk of destabilisation.

Evidence-based data for endometriosis management are limited. Experiments are excluded without adequate animal models. Data are limited to symptomatic women and occasional observations. Hormonal medical therapy cannot be blinded if recognised by the patient. Randomised controlled trials are not realistic for surgery, since endometriosis is a variable disease with low numbers. Each diagnosis and treatment is an experiment with an outcome, and experience is the means by which Bayesian updating, according to the past, takes place. If the experiences of many are similar, this holds more value than an opinion. The combined experience of a group of endometriosis surgeons was used to discuss problems in managing endometriosis. Considering endometriosis as several genetically/epigenetically different diseases is important for medical therapy. Imaging cannot exclude endometriosis, and diagnostic accuracy is limited for superficial lesions, deep lesions, and cystic corpora lutea. Surgery should not be avoided for emotional reasons. Shifting infertility treatment to IVF without considering fertility surgery is questionable. The concept of complete excision should be reconsidered. Surgeons should introduce quality control, and teaching should move to explain why this occurs. The perception of information has a personal bias. These are the major problems involved in managing endometriosis, as identified by the combined experience of the authors, who are endometriosis surgeons.

Segmental rectum resections for indications other than endometriosis were reported to result in up to 40% sexual dysfunctions. We, therefore, evaluated sexual function after low bowel resection (n = 33) for deep endometriosis in comparison with conservative excision (n = 23). Sexual function was evaluated with the FSFI-19 (Female Sexuality Functioning Index) and EHP 30 (Endometriosis Health Profile). The pain was evaluated with visual analogue scales. Linear excision and bowel resections improved FSFI, EHP 30, and postoperative pain comparably. By univariate analysis, a decreased sexual function was strongly associated with pain both before (p < 0.0001) and after surgery (p = 0.0012), age (p = 0.05), and duration of surgery (p = 0.023). By multivariate analysis (proc logistic), the FSFI after surgery was predicted only by FSFI before or EHP after surgery. No differences were found between low bowel segmental resection and a more conservative excision. In conclusion, improving pain after surgery can explain the improvement in sexual function. A deleterious effect of a bowel resection on sexual function was not observed for endometriosis. Sexual function in women with endometriosis can be evaluated using a simplified questionnaire such as FSFI-6.