Marina Yu Eliseeva

Severe inflammatory reaction induced by peritoneal trauma is the key driving mechanism of postoperative adhesion formation

BackgroundMany factors have been put forward as a driving mechanism of surgery-triggered adhesion formation (AF). In this study, we underline the key role of specific surgical trauma related with open surgery (OS) and laparoscopic (LS) conditions in postoperative AF and we aimed to study peritoneal tissue inflammatory reaction (TIR), remodelling specific complications of open surgery (OS) versus LS and subsequently evaluating AF induced by these conditions.MethodsA prospective randomized study was done in 80 anaesthetised female Wistar rats divided equally into 2 groups. Specific traumatic OS conditions were induced by midline incision line (MIL) extension and tissue drying and specific LS conditions were remodelled by intraperitoneal CO2 insufflation at the 10 cm of water. TIR was evaluated at the 24th, 72nd, 120th and 168th hour by scoring scale. Statistical analysis was performed by the non-parametric t test and two-way ANOVA using Bonferroni post-tests.ResultsMore pronounced residual TIR was registered after OS than after LS. There were no significant TIR interactions though highly significant differences were observed between the OS and LS groups (p < 0.0001) with regard to surgical and time factors. The TIR change differences between the OS and LS groups were pronounced with postoperative time p < 0.05 at the 24th and 72nd; p < 0.01 - 120th and p < 0.001 - 168th hrs. Adhesion free wounds were observed in 20.0 and 31.0% of cases after creation of OS and LS conditions respectively; with no significant differences between these values (p > 0.05). However larger adhesion size (41.67 ± 33.63) was observed after OS in comparison with LS (20.31 ± 16.38). The upper-lower 95% confidential limits ranged from 60.29 to 23.04 and from 29.04 to 11.59 respectively after OS and LS groups with significant differences (p = 0.03). Analogous changes were observed in adhesion severity values. Subsequently, severe TIR parameters were followed by larger sizes of severe postoperative adhesions in the OS group than those observed in the LS group.ConclusionsMIL extension and tissue drying seem to be the key factors in the pathogenesis of adhesion formation, triggering severe inflammatory reactions of the peritoneal tissue surrounding the MIL resulting in local and systemic consequences. CO2 insufflation however, led to moderate inflammation and less adhesion formation.

A surgical polypragmasy: Koninckx PR, Corona R, Timmerman D, Verguts J, Adamyan L. Peritoneal full-conditioning reduces postoperative adhesions and pain: a randomised controlled trial in deep endometriosis surgery. J Ovarian Res. 2013 Dec 11;6(1):90

A surgical polypragmasy: Koninckx PR, Corona R, Timmerman D, Verguts J, Adamyan L. Peritoneal full-conditioning reduces postoperative adhesions and pain: a randomised controlled trial in deep endometriosis surgery. J Ovarian Res. 2013 Dec 11;6(1):90 Ospan A Mynbaev, Peter Biro, Marina Yu Eliseeva, Andrea Tinelli, Antonio Malvasi, Ioannis P Kosmas, Mykhailo V Medvediev, Tatiana I Babenko, Madina I Mazitova, Sergei S Simakov and Michael Stark

Challenging nanoparticles: a target of personalized adhesion prevention strategy.

Dear editor With great interest we have read an article by Wu et al1 recently published in the International Journal of Nanomedicine aimed to estimate cytotoxicity, toxicity, and histopathological changes, as well as the postsurgical antiadhesion potential of biodegradable and thermosensitive micelles by combining in vitro and in vivo models. Our congratulations to Wu et al1 for their new, precisely designed, and promising study of nanoparticles used in the prevention of postsurgical adhesions. Even more so when we know that in most clinical studies the adhesion prevention adjuvants have failed. Taking into account medical and financial problems associated with postsurgical adhesions worldwide in the health care system, new developments in this area are welcomed and call for further investigation. We do not question the definite study question and design: the experimental models are precisely formed and trigger correctly described results, a knowledgeable discussion and subsequent reasonable conclusions in line with their achievements. However, in our opinion, for these biodegradable and thermosensitive micelles to be recommended for further clinical applications, experimental studies should be designed examining different doses of nanoparticles in order to establish the optimal dose of micelles, an evaluation of the impact of these materials in different time points after their application, ie, 14, 21, 28 days, as well as their long-term impact after 6 and 12 months. The impact of these particles on embryos in in vivo models should also be evaluated: do these particles last longer or do they have an impact on uterine wall tissue? In the future a personalized adhesion prevention strategy could be developed, with application of state of the art technologies, taking into account genetic and constitutional predisposing factors of the patients undergoing these surgical procedures, with targeted predisposing genetic and constitutional conditions.2 Subsequently, these biodegradable and self-assembling micelles could be designed to contain medication such as recombinant tissue plasminogen activator (rtPA),3 tPA genes, inhibitors of plasminogen activator inhibitor-1 (PAI-1) genes, or other cytokines activating the expression of individually targeted genes at certain times after surgery in order to lyse and remove temporary fibrinogenous adhesions. In conclusion, biodegradable micelles containing certain medications should be a basis for future personalized adhesion prevention strategies.

Inhibition of oxygen scavengers realized by peritoneal macrophages: an adhesion prevention target?

© 2014 Mynbaev et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php

Microsurgical principles should be considered in studies addressing adhesion prevention: Cağlar et al. (2014)

With great interest we have read an article by Cağlar et al. [1], recently published in your journal. The authors aimed to present the impact of a gelatin–thrombin matrix application on postsurgical adhesion formation in a rat model. We are grateful for their attempt to shed some light on the impact of a gelatin–thrombin matrix application on postsurgical adhesion formation scores, inflammation biochemical markers’ changes and fibrosis extension. However, according to microsurgery principles, the application of sealants and gels on damaged-bleeding surfaces should be avoided since this triggers severe postsurgical inflammation and tissue reaction against foreign bodies [2, 3]. Moreover, this reaction is amplified by a combination of coagulation traumas. In the authors’ statement a question is formulated as: ‘‘There are reports indicating that gelatin– thrombin matrix is an effective hemostatic agent in gynecologic procedures, infertility, gyneco-oncologic procedures, and postpartum hemorrhage’’. However, in all studies cited by the authors this kind of hemostatic products have been applied for urgent surgical procedures to stop bleeding during postpartum hemorrhage [4, 5], tubal ectopic pregnancy [6], and also for myomectomy [7]. Moreover, two citations describe bowel obstruction associated with the use of a gelatin–thrombin matrix [8] and the application of Flo-Seal product [9]. The application of these materials was aimed to reduce or stop bleedings. Therefore, according to microsurgical principles, we can expect extensive fibrinogenous adhesion formation and this was proved by the findings of Hoffmann et al. [10]: a gelatin–thrombin matrix increases postsurgical adhesion formation. We do not have any objections concerning their results and discussion [1] but in our opinion the hypothesis in the present article is vague as well as the study which was not properly designed: no sample size calculation nor power analysis. We think that the authors when they designed their project should have studied literature more extensively, taking into account microsurgical principles in order

Case Report of Combined Twin Tubal and Intrauterine Pregnancies

Case of heterotopic quadruplet pregnancy with coexistence of tubal and intrauterine twins. Objective (s): To present the case heterotopic quadruplet pregnancy with coexistence of tubal and intrauterine twins and its successful surgical management with brief literature review. Design: A case report supplemented with brief literature review and discussion. Setting: City clinical university hospital. Patient (s): Heterotopic quadruplet pregnancy with tubal and intrauterine twins in a 31-year-old woman after natural conception. Intervention (s): Laparoscopy, adhesiolisys, aspiration of tubal embryos through tubotomy and cervical dilatation and vacuum aspiration of intrauterine embryos as well as vaginal and intraoperative laparoscopic ultrasound examination. Main outcome measure (s): Physical examination, laparoscopy and postsurgical hCG serum assay, as well as preintra- and postoperative vaginal ultrasound and intraoperative laparoscopic sonography. Result (s): Successful diagnosis and treatment of a case of heterotopic quadruplet pregnancy with coexistence of tubal and intrauterine twins in a 31-year-old woman with 6 artificial abortions, pelvic inflammatory diseases and periadnexal adhesions, after natural conception was described. An intraoperative laparoscopic sonography was applied to complete diagnosis of heterotopic pregnancy with coexistence of tubal and intrauterine twins after control of bleeding and stabilization of patient condition due to necessity to perform an emergency surgery. The case was supplemented with a brief review of literature and discussion. Conclusion (s): A unique case of heterotopic quadruplet pregnancy with coexistence of tubal and intrauterine twins after natural conception was presented in the first time.

Uterine-preserving operative therapy of uterus myomatosus

Uterine myomas are the most frequent benign tumours of the uterus in women of childbearing age. Although uterine fibroids cause symptoms in only 20–50 % of cases, if present they may cause abnormal uterine bleeding, pain, and infertility.

Work of separation - A method to assess intraperitoneal adhesion and healing of parietal peritoneum in an animal model.

• Intraperitoneal adhesions are remaining a heavy financial burden for the health care systems.

Docetaxel-loaded solid lipid nanoparticles as a basis for a targeted and dose-sparing personalized breast cancer treatment strategy

Dear editor The long-term survival rate of patients with breast cancer was improved by the application of systemic adjuvant chemotherapy,1 although the primary breast cancer treatment strategy consists of mastectomy with lymphadenectomy and radiotherapy followed by breast reconstruction.2–5 Unfortunately, most adjuvant chemotherapeutic agents trigger major side effects.1,6 Therefore, we have read with great interest an article in the International Journal of Nanomedicine on the design of docetaxel-loaded solid lipid nanoparticles (DSNs) aimed at reducing the systemic toxicity of standardized docetaxel treatment.7 Our congratulation to the authors7 for their clear demonstration of the reduced cytotoxicity of DSNs and significantly decreased myelosuppressive toxicity by recovering the proliferation and differentiation of bone marrow progenitor cells, while triggering more apoptosis in MCF-7 cells at a low dose compared with the commercial formula of docetaxel by an arrested cell cycle progression in the G2/M stage. The acute necessity for such state-of-the-art studies is linked to a high worldwide incidence of breast cancer; in the World Health Organization Fact sheet, its increased metastatic potency is listed as one of the most common causes of cancer death.8 The incidence of breast cancer is high in Western European countries, ie, about 89.7 per 100,000 women.8 The same high incidence applies to other developed countries. For our part, we have analyzed the statistical data concerning breast cancer in the Russian Federation.9 According to the statistical report by the Federal Research Institute for Health Organization and Informatics of the Ministry of Health of the Russian Federation between 2003 and 2012 (Table 1), the 10-year breast cancer incidence rates average 68.99 per 100,000 women (an average of 52,647 women annually), of which 95.1% cases were histologically verified. The average 5-year survival rate was 56.2% among women with breast cancer followed up in state and municipal cancer institutions. The average annual mortality of patients with verified breast cancer was 10.0% among individuals who were followed up in cancer institutes. Subsequently, between 2003 and 2012, about 25,697 women per year died of breast cancer in the Russian Federation. Table 1 Modified data from a statistical report for 2012 by the Federal Research Institute for Health Organization and Informatics of the Ministry of Health of the Russian Federation Our investigation, as proved by time series analysis (JMP7 software), revealed that the incidence of breast cancer had been rising continually, with increasing trends from 2003 to 2012 while at the same time the number of cancer deaths has been steadily decreasing (Table 1). Overall, the same trends exist for all cancer patients, in the same time. This phenomenon can be explained first by improvements in the Russian health care system. Government programs were set up applying new diagnostic technologies for early breast cancer screening, and preventive medical strategies were encouraged. Second, the rise in incidence of breast cancer might also be associated with gradual lifestyle changes. Many mothers in Russia decline breastfeeding and, in addition, worldwide environmental changes are reflected in an increased incidence of breast cancer, including in countries with a low prevalence of the disease. This brief analysis demonstrates that our modern community calls for new therapeutic approaches in the treatment of breast cancer. We believe that further studies could show the application of DSNs to be a basic compound for a targeted and dose-sparing personalized breast cancer treatment strategy.

Comment on “Prospective Experimental Study to Investigate the Peritoneal Adhesion Formation of Argon Plasma Coagulation (APC) Versus a Novel Aerosol Plasma in a Rat Model”

Dear Editor, We deeply appreciate Kraemer et al for an excellent study published in your journal. Many products have already been suggested to prevent adhesions but none has proved to be the optimal one. This is probably because of the complexity of the etiology and the pathogenesis of postsurgical adhesions. The impact of acute inflammation induced by surgical trauma seems to be an important mechanism to cause adhesion. The present study confirms our own hypothesis and even extends it by suggesting strategy to prevent adhesions by limiting surgical trauma, using a new device in this well-designed experimental study. The results are well illustrated with explanation of the aerosol plasma-device mechanism compared with those of an argon plasma coagulator, and presenting benefits and highlighting limitations of these methods in their discussion. Both quantitative and qualitative properties of postsurgical adhesions were significantly decreased after using aerosol plasma compared with those when argon plasma is used. This can be confirmed by stronger carbonization with dark brown color in the lesion induced by argon plasma and slightly superficial yellow lesionsinduced by aerosol plasma coagulation (Figure 2). However, the weak insignificant differences shown in the histological results between the groups and the absence of interactions were probably related to the relatively long duration of the postsurgical follow-up period when an acute inflammation is diminished in very small injured areas according to the diameter of the metallic item (Figure 2). The local histological changes were not evaluated by quantitative and qualitative approach since the parameters (size and thickness) of adhesions covered argon plasma lesions were evidently more pronounced than those of aerosol plasma lesions (Figure 4). We believe that if the authors had used the similar study design as our study and evaluated changes macroscopically during acute inflammation or by using cytological and histological scores and immunohistohemistry, and if they had used scanning electron microscopy, they could have shown significant differences between these 2 methods. Nevertheless, we believe that it is time to initiate a debate concerning the overuse of argon plasma coagulation during abdominal and pelvic surgeries, a usage initiated by the medical device manufacturer with its associated surgeons, despite the lack of evidence-based studies. Argon plasma coagulation has even been recommended for routine use even to dry the suture line of the uterus during cesarean section (presented in video) and in other surgical procedures through poorly designed publications suggesting an absence of adhesions and other postsurgical complications. This campaign is promoted by a well-organized marketing policy through conferences, non-peer-reviewed journals, and the Web. We believe that any surgical tool and/or instrument should only be used after they have been proven to add value to existing ones, and even then should be used properly to minimize side effects, and decisions concerning introduction of new tools should be free of any commercial interests. Therefore, well-designed studies of new surgical tools and instruments are needed. The 521018 SRIXXX10.1177/1553350614521018Surgical InnovationMynbaev et al research-article2014