Letters to the Editors However, diagnostic laparoscopy and diagnostic hysteroscopy would not be included because of the slippery slope that might tempt office gynecologists to undertake more complex procedures for which they were not fully trained. In my community there seems to be a voluntary selection into these categories dictated by areas of clinical interest, years in practice, and lifestyle desires. If during the residency years an appropriate distribution cannot be attained, then a pyramid structure could be designed similar to the one that exists in general surgery. Lastly, an equitable compensation system would have to be devised so residents could make their decision based on their area of interest as opposed to their financial security. David Newfield, MD Department of Obstetrics and Gynecology Providence St. Joseph Medical Center 501 South Buena Vista Street Burbank, CA 91505
[email protected] The author reports no conflict of interest.
REFERENCE 1. Walter A. Every woman deserves a high-volume gynecologic surgeon. Am J Obstet Gynecol 2016;216:139-40. ª 2017 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog. 2017.06.022
REPLY I appreciate the opportunity to respond to Dr Newfield’s comments regarding my commentary on low-volume gynecological surgeons. I agree completely that modifying the existing residencies in obstetrics and gynecology by creating a tracking program based on the residents’ desires and proclivities would be an excellent solution to the current issue. I recently gave a lecture in which I outlined a thought experiment I performed regarding the residency program
ajog.org with which I am affiliated. Specifically, in this thought experiment, I restructured the residency so that postgraduate years 1 and 2 were the same for all 6 residents, and then starting postgraduate year 3, the group was divided into 4 clinic/obstetrics residents with a planned 2 additional years of training and 2 gynecological surgery residents for a planned 3 additional years of training focused only on surgery. Based on the current residents’ surgical numbers, this tracking would increase the number of cases per resident 3- to 5-fold (ie, in this model, endoscopic hysterectomy went from an average 83 to 243 and vaginal hysterectomy increased from 35 to 130 cases per 4 years). These higher numbers are more consistent with the learning curve required to be proficient with these procedures (as outlined in the Clinical Commentary) and would increase training costs by only 8% (24 vs 26 resident years). Unfortunately, the barriers to establishing such a program, which include how residents are tracked to become a surgeon vs clinician, what these tracked residents do after graduation and what becomes of obstetricians-gynecologists who previously trained in a nontracked residency among others are likely insurmountable, at least during my practice lifetime. Because this is in the best interest of our patients, I encourage all practicing obstetricians-gynecologists to work within their practices and hospitals as well as with the payers, American Board of Obstetrics and Gynecology, and/or American College of Obstetricians and Gynecologists to develop equitable and workable solutions (which may ultimately include some version of tracking) to the problem of low-volume surgeons. Andrew Walter, MD Director of Urogynecology and Pelvic Pain Kaiser North Valley MOB2/3C 1600 Eureka Road Roseville, CA 95661
[email protected] The authors report no conflict of interest. ª 2017 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog. 2017.06.023
Oxidative stress and inflammatory biomarkers in normal and preeclamptic pregnancies TO THE EDITORS: I read with interest the article by Ferguson et al,1 which reports on 2 urinary metabolites as indicators of oxidative stress: 8-isoprostane, a marker of lipid peroxidation, and 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage. The authors constantly found the 8-isoprostane to be elevated and yet the 8-OHdG to be decreased throughout preeclamptic pregnancy but give no clear explanation to opposing findings. 492 American Journal of Obstetrics & Gynecology OCTOBER 2017
My model of the pathogenesis of preeclampsia2 (PE) is as follows: PE is a disease of oxidative stress resulting from the catabolism of DNA (primarily fetal) to uric acid by xanthine oxidase (XO) in the maternal liver. This model can offer an explanation. But first, it is important to mention the model of Redman and Sargent3 of a 2-stage disorder of PE in which the first stage is reduced placental perfusion (vascular) and the second
Letters to the Editors
ajog.org stage, the maternal syndrome, is due to inflammation/ oxidative stress. Second, it important to note that xanthine oxidoreductase has 2 isoenzymes: xanthine dehydrogenase (XDH) and XO. The dehydrogenase is the most commonly active form of the enzyme, although this can be converted to the oxidase. XO is the more toxic of these isoenzymes because it produces reactive oxygen species (ROS).4 Only about one third of pregnant women with reduced placental perfusion go on to develop PE.5 According to my model of PE,2 this is because they produce uric acid via XO, whereas those who do not develop PE use the XDH isoenzyme. So, how do we explain the data of Ferguson et al,1 that 8OHdG, a biomarker of oxidative stress, is decreased throughout a preeclamptic pregnancy? Guanosine is a purine nucleoside and as such is a substrate for xanthine oxidoreductase. But XDH has only 25% of the maximal velocity of XO,6 so guanosine would be more rapidly broken down by the patients with PE. Thus, 8-OHdG was probably an unfortunate choice as a biomarker of oxidative stress in this setting of PE. Interestingly, Ferguson et al1 found that “the start of the second trimester appears to be a particularly important time point for the measurement of these biomarkers.” Their data on 8-isoprostane indicate that oxidative stress is occurring in reduced placental perfusion stage, but this disagrees with the model of Redman and Sargent,3 whereas these data would fit my model2 in which the substrate of XO is the cell-free fetal DNA from the trophoblast in the placental perfusion phase. With my model, the primary oxidative stress in PE occurs from the catabolism of cell-free fetal DNA in the maternal liver. This stress is coped with by maternal natural antioxidants. The balance is tipped once maternal tissues become injured by the ROS. Both the 8-isoprostane data of Ferguson et al1 and my model would be in agreement with the proposal of Roberts and Hubel7, that oxidative stress could be the link in the 2-stage model of PE.
My model2 proposes that it is the maternal hepatocytes that are primarily injured from the production of ROS. The ROS then leak into the maternal circulation, damaging the white blood cells (WBCs) and endothelial cells. It is probably that the maternal WBCs are the main source of the cell-free DNA in the maternal phase of PE. The damage to the WBCs would lead to the release of inflammatory markers into the maternal circulation. Thus, this perceived inflammation is probably a consequence of the systemic oxidative stress in PE. Roger A. McMaster-Fay, MB, BS Department of Obstetrics and Gynaecology Faculty of Medicine Central Clinical University of Sydney PO Box 82, Emu Plains Sydney, New South Wales 2750, Australia The author reports no conflict of interest.
REFERENCES 1. Ferguson KK, Meeker JD, McElrath F, Mukherjee B, Cantonwine DE. Repeated measures of inflammation and oxidative stress biomarkers in preeclampsia and normotensive pregnancies. Am J Obstet Gynecol 2017;216:527.e1-9. 2. McMaster-Fay RA. Pre-eclampsia: a disease of oxidative stress resulting from the catabolism of DNA (primarily fetal) to uric acid by xanthine oxidase in the maternal liver: a hypothesis. Biosci Hypotheses 2008;1:35-43. 3. Redman CWG, Sargent IL. Pre-eclampsia, the placenta and the maternal systemic inflammatory response. Placenta 2003;24:S21-7. 4. Berry CE, Hare JM. Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications. J Physiol 2004;555:589-606. 5. Bower S, Bewley S, Campbell S. Improved prediction of preeclampsia by two-stage screening of uterine arteries using early diastolic notch and color Doppler imaging. Obstet Gynecol 1993;82:78-83. 6. Saito T, Nishino T. Difference in redox and kinetic properties between NAD-dependant and O2-dependant types of rat liver xanthine dehydrogenase. J Biol Chem 1989;264:10015-22. 7. Roberts JM, Hubel CA. Is oxidative stress the link in the two stage model of pre-eclampsia? Lancet 1999;354:788-9. ª 2017 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog. 2017.06.030
Identifying the vaginal fornix in cesarean hysterectomy for an abnormally invasive placenta: an alternative technique TO THE EDITORS: In cesarean hysterectomy for an abnormally invasive placenta, Belfort and colleagues1 placed a round metallic bowel end-to-end anastomosis (EEA) sizer at the anterior/posterior fornix. This indicates the site to be incised. I devised another method to identify the fornix.2,3 The anterior and posterior cervices are closed using a round forceps before surgery. Surgeons can discern the metal hardness of the forceps from the abdominal/pelvic side (Figure).2,3 This
“holding the cervix (HC)” may have merits over EEA-sizer method. Firstly, in HC, the forceps are in place and continue to indicate the site throughout the surgery, whereas the EEA sizer should be inserted at the time of vaginal wall transection, usually after bladder separation. For less experienced surgeons, judgment of its separation depth is difficult. The metal hardness is discernable even before bladder separation and, thus, it OCTOBER 2017 American Journal of Obstetrics & Gynecology
493
