Ally Murji

The Management of Uterine Leiomyomas

OBJECTIVES The aim of this guideline is to provide clinicians with an understanding of the pathophysiology, prevalence, and clinical significance of myomata and the best evidence available on treatment modalities. OPTIONS The areas of clinical practice considered in formulating this guideline were assessment, medical treatments, conservative treatments of myolysis, selective uterine artery occlusion, and surgical alternatives including myomectomy and hysterectomy. The risk-to-benefit ratio must be examined individually by the woman and her health care provider. OUTCOMES Implementation of this guideline should optimize the decision-making process of women and their health care providers in proceeding with further investigation or therapy for uterine leiomyomas, having considered the disease process and available treatment options, and reviewed the risks and anticipated benefits. EVIDENCE Published literature was retrieved through searches of PubMed, CINAHL, and Cochrane Systematic Reviews in February 2013, using appropriate controlled vocabulary (uterine fibroids, myoma, leiomyoma, myomectomy, myolysis, heavy menstrual bleeding, and menorrhagia) and key words (myoma, leiomyoma, fibroid, myomectomy, uterine artery embolization, hysterectomy, heavy menstrual bleeding, menorrhagia). The reference lists of articles identified were also searched for other relevant publications. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date limits but results were limited to English or French language materials. Searches were updated on a regular basis and incorporated in the guideline to January 2014. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, and national and international medical specialty societies. BENEFITS, HARMS, AND COSTS The majority of fibroids are asymptomatic and require no intervention or further investigations. For symptomatic fibroids such as those causing menstrual abnormalities (e.g. heavy, irregular, and prolonged uterine bleeding), iron defficiency anemia, or bulk symptoms (e.g., pelvic pressure/pain, obstructive symptoms), hysterectomy is a definitive solution. However, it is not the preferred solution for women who wish to preserve fertility and/or their uterus. The selected treatment should be directed towards an improvement in symptomatology and quality of life. The cost of the therapy to the health care system and to women with fibroids must be interpreted in the context of the cost of untreated disease conditions and the cost of ongoing or repeat investigative or treatment modalities. VALUES The quality of evidence in this document was rated using the criteria described in the Report of the Caadian Task Force on Preventive Health Care (Table 1). Summary Statements 1. Uterine fibroids are common, appearing in 70% of women by age 50; the 20% to 50% that are symptomatic have considerable social and economic impact in Canada. (II-3) 2. The presence of uterine fibroids can lead to a variety of clinical challenges. (III) 3. Concern about possible complications related to fibroids in pregnancy is not an indication for myomectomy except in women who have had a previous pregnancy with complications related to these fibroids. (III) 4. Women who have fibroids detected in pregnancy may require additional maternal and fetal surveillance. (II-2) 5. Effective medical treatments for women with abnormal uterine bleeding associated with uterine fibroids include the levonorgestrel intrauterine system, (I) gonadotropin-releasing hormone analogues, (I) selective progesterone receptor modulators, (I) oral contraceptives, (II-2) progestins, (II-2) and danazol. (II-2) 6. Effective medical treatments for women with bulk symptoms associated with fibroids include selective progesterone receptor modulators and gonadotropin-releasing hormone analogues. (I) 7. Hysterectomy is the most effective treatment for symptomatic uterine fibroids. (III) 8. Myomectomy is an option for women who wish to preserve their uterus or enhance fertility, but carries the potential for further intervention. (II-2) 9. Of the conservative interventional treatments currently available, uterine artery embolization has the longest track record and has been shown to be effective in properly selected patients. (II-3) 10. Newer focused energy delivery methods are promising but lack long-term data. (III) Recommendations 1. Women with asymptomatic fibroids should be reassured that there is no evidence to substantiate major concern about malignancy and that hysterectomy is not indicated. (III-D) 2. Treatment of women with uterine leiomyomas must be individualized based on symptomatology, size and location of fibroids, age, need and desire of the patient to preserve fertility or the uterus, the availability of therapy, and the experience of the therapist. (III-B) 3. In women who do not wish to preserve fertility and/or their uterus and who have been counselled regarding the alternatives and risks, hysterectomy by the least invasive approach possible may be offered as the definitive treatment for symptomatic uterine fibroids and is associated with a high level of satisfaction. (II-2A) 4. Hysteroscopic myomectomy should be considered first-line conservative surgical therapy for the management of symptomatic intracavitary fibroids. (II-3A) 5. Surgical planning for myomectomy should be based on mapping the location, size, and number of fibroids with the help of appropriate imaging. (III-A) 6. When morcellation is necessary to remove the specimen, the patient should be informed about possible risks and complications, including the fact that in rare cases fibroid(s) may contain unexpected malignancy and that laparoscopic power morcellation may spread the cancer, potentially worsening their prognosis. (III-B) 7. Anemia should be corrected prior to proceeding with elective surgery. (II-2A) Selective progesterone receptor modulators and gonadotropin-releasing hormone analogues are effective at correcting anemia and should be considered preoperatively in anemic patients. (I-A) 8. Use of vasopressin, bupivacaine and epinephrine, misoprostol, peri-cervical tourniquet, or gelatin-thrombin matrix reduce blood loss at myomectomy and should be considered. (I-A) 9. Uterine artery occlusion by embolization or surgical methods may be offered to selected women with symptomatic uterine fibroids who wish to preserve their uterus. Women choosing uterine artery occlusion for the treatment of fibroids should be counselled regarding possible risks, including the likelihood that fecundity and pregnancy may be impacted. (II-3A) 10. In women who present with acute uterine bleeding associated with uterine fibroids, conservative management with estrogens, selective progesterone receptor modulators, antifibrinolytics, Foley catheter tamponade, and/or operative hysteroscopic intervention may be considered, but hysterectomy may become necessary in some cases. In centres where available, intervention by uterine artery embolization may be considered. (III-B).

Single-incision laparoscopy in gynecologic surgery: a systematic review and meta-analysis.

OBJECTIVE: To evaluate surgical outcomes for gynecologic surgery performed by single-incision laparoscopy compared with conventional multi-incision laparoscopy. DATA SOURCES: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and clinicaltrials.gov through August 2012. We also screened reference lists of retrieved articles and manually searched abstracts from conference proceedings. METHODS OF STUDY SELECTION: We included randomized control trials (RCTs) and high-quality observational studies that compared outcomes for single-incision laparoscopy and conventional laparoscopy for gynecologic surgery in patients. Included studies met predefined quality criteria and reported, at minimum, on complications, conversions, and operative time. TABULATION, INTEGRATION, RESULTS: Six RCTs and 15 observational studies met inclusion criteria, with a total of 2,085 patients (899 single-incision laparoscopies and 1,186 conventional laparoscopies). In the pooled analysis, there was no significant difference in the risk of total complications between single-incision laparoscopy and conventional laparoscopy groups (relative risk 1.01, 95% confidence interval [CI] 0.72–1.40; P=.97, random effects model). The meta-analysis was powered to detect a 5% difference in complications (power=0.8, alpha=0.05). Mean operative time for adnexal surgery performed by single-incision laparoscopy was 6.97 minutes longer than conventional laparoscopy (95% CI 0.16–13.77; P=.045; I2=47.2; random effects based on three RCTs). There was no significant difference in mean operative time for hysterectomy procedures performed by single-incision laparoscopy (8.29 minutes, 95% CI −5.85 to 22.43; P=.251; I2=83.6; random effects based on three RCTs). Clinical outcomes of postoperative pain, change in hemoglobin, length of hospital stay, and scar cosmesis could not be pooled because of paucity of data and lack of uniform reporting. CONCLUSION: There was no difference in the risk of complications between single-incision laparoscopy and conventional laparoscopy approaches in gynecologic surgery. Studies with imprecise effect sizes suggest that single-incision laparoscopy may have longer operative time for adnexal surgery, but not for hysterectomy. Effects on other surgical outcomes remain uncertain.

Bone Invasion in Extremity Soft-Tissue Sarcoma Impact on Disease Outcomes

The purpose of the current study was to evaluate histologic bone invasion as a predictor of oncologic outcome in extremity soft‐tissue sarcoma (STS) patients presenting to a specialty sarcoma center between 1986 and 2001.

Male sex bias in placental dysfunction

Several reports suggest a male fetal preponderance in a variety of complications of pregnancy attributable to severe placental dysfunction (SPD). However, the underlying mechanisms remain unknown. Our primary objective was to explore the relationship between fetal sex and the spectrum of conditions implicated in abnormal placentation. We identified singleton pregnancies with a fetus delivered between 20 + 0 and 32 + 6 weeks of gestation with one or more pregnancy complications attributed to SPD (severe pre‐eclampsia, intra‐uterine fetal death, intra‐uterine growth restriction, abnormal Doppler studies, abruption) at a single institution between 1999 and 2007. Pedigrees of index cases were created to define the relationship between fetal sex and the risk of SPD. We identified 132 index cases, 97/132 (73%) were male. Eighty‐four index cases had a total of 133 sibs, of which 37/133 (28%) were affected with SPD (22 male, 15 female). A male sex preponderance persisted across all manifestations of PD in index cases with sibs. In families with the absence of maternal chronic hypertension (cHTN; n = 70), the index case was 5.9 (95% CI 2.28–16.15; P <0.001) times more likely to be male and most (12/14) affected sibs of male index cases were male, while female index cases had no affected sibs. Our results confirm a male fetal sex preponderance in SPD. In a subgroup analysis of families without cHTN, a significant male bias was found to extend to sibs of index cases. This suggests a potential genetic mechanism predisposing the male fetus to abnormal placental development.

Endometrial Ablation in the Management of Abnormal Uterine Bleeding

BACKGROUND Abnormal uterine bleeding (AUB) is the direct cause of a significant health care burden for women, their families, and society as a whole. Up to 30% of women will seek medical assistance for the problem during their reproductive years. OBJECTIVE To provide current evidence-based guidelines on the techniques and technologies used in endometrial ablation (EA), a minimally invasive technique for the management of AUB of benign origin. METHODS Members of the guideline committee were selected on the basis of individual expertise to represent a range of practical and academic experience in terms of both location in Canada and type of practice, as well as subspecialty expertise and general background in gynaecology. The committee reviewed all available evidence in the English medical literature, including published guidelines, and evaluated surgical and patient outcomes for the various EA techniques. Recommendations were established by consensus. EVIDENCE Published literature was retrieved through searches of MEDLINE and The Cochrane Library in 2013 and 2014 using appropriate controlled vocabulary and key words (endometrial ablation, hysteroscopy, menorrhagia, heavy menstrual bleeding, AUB, hysterectomy). RESULTS were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies written in English from January 2000 to November 2014. Searches were updated on a regular basis and incorporated in the guideline to December 2014. Grey (unpublished) literature was identifies through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. VALUES The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). RESULTS This document reviews the evidence regarding the available techniques and technologies for EA, preoperative and postoperative care, operative set-up, anaesthesia, and practical considerations for practice. BENEFITS, HARMS, AND COSTS Implementation of the guideline recommendations will improve the provision of EA as an effective treatment of AUB. Following these recommendations would allow the surgical procedure to be performed safely and maximize success for patients. CONCLUSIONS EA is a safe and effective minimally invasive option for the treatment of AUB of benign etiology. Summary Statements 1. Endometrial ablation is a safe and effective minimally invasive surgical procedure that has become a well-established alternative to medical treatment or hysterectomy to treat abnormal uterine bleeding in select cases. (I) 2. Endometrial preparation can be used to facilitate resectoscopic endometrial ablation (EA) and can be considered for some non-resectoscopic techniques. For resectoscopic EA, preoperative endometrial thinning results in higher short-term amenorrhea rates, decreased irrigant fluid absorption, and shorter operative time than no treatment. (I) 3. Non-resectoscopic techniques are technically easier to perform than resectoscopic techniques, have shorter operative times, and allow the use of local rather than general anaesthesia. However, both techniques have comparable patient satisfaction and reduction of heavy menstrual bleeding. (I) 4. Both resectoscopic and non-resectoscopic endometrial ablation (EA) have low complication rates. Uterine perforation, fluid overload, hematometra, and cervical lacerations are more common with resectoscopic EA; perioperative nausea/vomiting, uterine cramping, and pain are more common with non-resectoscopic EA. (I) 5. All non-resectoscopic endometrial ablation devices available in Canada have demonstrated effectiveness in decreasing menstrual flow and result in high patient satisfaction. The choice of which device to use depends primarily on surgical judgement and the availability of resources. (I) 6. The use of local anaesthetic and blocks, oral analgesia, and conscious sedation allows for the provision of non-resectoscopic EA in lower resource-intense environments including regulated non-hospital settings. (II-2) 7. Low-risk patients with satisfactory pain tolerance are good candidates to undergo endometrial ablation in settings outside the operating room or in free-standing surgical centres. (II-2) 8. Both resectoscopic and non-resectoscopic endometrial ablation are relatively safe procedures with low complication rates. The complications perforation with potential injury to contiguous structures, hemorrhage, and infection. (II-2) 9. Combined hysteroscopic sterilization and endometrial ablation can be safe and efficacious while favouring a minimally invasive approach. (II-2) Recommendations 1. Preoperative assessment should be comprehensive to rule out any contraindication to endometrial ablation. (II-2A) 2. Patients should be counselled about the need for permanent contraception following endometrial ablation. (II-2B) 3. Recommended evaluations for abnormal uterine bleeding, including but not limited to endometrial sampling and an assessment of the uterine cavity, are necessary components of the preoperative assessment. (II-2B) 4. Clinicians should be vigilant for complications unique to resectoscopic endometrial ablation such as those related to fluid distention media and electrosurgical injuries. (III-A) 5. For resectoscopic endometrial ablation, a strict protocol should be followed for fluid monitoring and management to minimize the risk of complications of distension medium overload. (III-A) 6. If uterine perforation is suspected to have occurred during cervical dilatation or with the resectoscope (without electrosurgery), the procedure should be abandoned and the patient should be closely monitored for signs of intraperitoneal hemorrhage or visceral injury. If the perforation occurs with electrosurgery or if the mechanism of perforation is uncertain, abdominal exploration is warranted to obtain hemostasis and rule out visceral injury. (III-B) 7. With resectoscopic endometrial ablation, if uterine perforation has been ruled out acute hemorrhage may be managed by using intrauterine Foley balloon tamponade, injecting intracervical vasopressors, or administering rectal misoprostol. (III-B) 8. If repeat endometrial ablation (EA) is considered following non-resectoscopic or resectoscopic EA, it should be performed by a hysteroscopic surgeon with direct visualization of the cavity. Patients should be counselled about the increased risk of complications with repeat EA. (II-2A) 9. If significant intracavitary pathology is present, resectoscopic endometrial ablation combined with hysteroscopic myomectomy or polypectomy should be considered in a non-fertility sparing setting. (II-3A).

The Role of Intraoperative Frozen Section Histology in Obstetrical Brachial Plexus Reconstruction

The use of frozen section histological analysis in primary obstetrical brachial plexus palsy reconstruction, though widespread, is not universally practiced. Our objective was to develop a histological grading scale that could be used to determine whether further resection of a microscopically suboptimal, though grossly satisfactory stump could lead to a measurable improvement in histological appearance. A 13-point grading tool assessing attributes of the epineurium, perineurium, and endoneurium was tested for interrater reliability. The histological appearance of initial nerve biopsies and of subsequent nerve reexcisions stained with toluidine blue was reviewed retrospectively (n = 52). Specimens were graded in a blinded fashion by a neuropathologist and a medical student. There was high agreement between expert and novice global rating scores with an intraclass correlation coefficient of 0.89 (95% confidence interval 0.85 to 0.93). A comparison of scores between subsequent sections of the same nerve stump revealed a significant decrease of 3.00 (expert) and 2.00 (novice) points ( P < 0.001) in the median global rating score, demonstrating improvement in histological grade. The novel grading tool was used to demonstrate that recutting a microscopically poor, though grossly acceptable nerve stump in obstetrical palsy surgery can yield a significantly improved histological grade.

Conservative Management of Cervical Ectopic Pregnancy

OBJECTIVE To evaluate the safety and effectiveness of conservative management for cervical ectopic pregnancies. METHODS We conducted a retrospective review of all cases of cervical ectopic pregnancy diagnosed at our tertiary care academic centre between January 2002 and July 2014. The diagnosis of cervical ectopic pregnancy was made using transvaginal ultrasound according to published criteria. Management decisions were made by individual clinicians. RESULTS Cervical ectopic pregnancy was diagnosed in 27 women with a median age of 34 years. Two thirds of them were nulliparous, and 44% (12/27) reported infertility. The mean gestational age at diagnosis was seven weeks. The median serum human chorionic gonadotropin level was 11 300 IU/L (range 610 to 163 700). Fetal cardiac activity was present in 19 pregnancies (70%). Vaginal bleeding was the most common presentation, occurring in 23 cases (85%). Three women presented with acute life-threatening hemorrhage. All cases were successfully managed conservatively, allowing uterine preservation. Systemic methotrexate (single or multi-dose protocol) was the mainstay of therapy. Other minimally invasive interventions included ultrasound-guided injection of potassium chloride into the pregnancy, uterine artery embolization, vaginal ligation of cervical branches of the uterine arteries, and dilatation and curettage, with or without dilute vasopressin cervical infiltration and Foley catheter tamponade. CONCLUSION Systemic methotrexate alone or in combination with other minimally invasive techniques can be effective conservative treatment for cervical pregnancies. A fertility-sparing approach is the optimal treatment for this patient population, which has high rates of infertility and nulliparity. We present a management algorithm based on our results to aid in standardizing the management of cervical ectopic pregnancies.

Propylthiouracil-induced agranulocytosis in the third trimester of pregnancy.

BACKGROUND: Thionamide-induced agranulocytosis in pregnancy is a rare event that poses unique therapeutic challenges. CASE: A 37-year-old woman developed agranulocytosis while taking propylthiouracil in the third trimester. After she took broad-spectrum antibiotics and discontinued propylthiouracil, her neutrophil counts recovered. She was initially managed expectantly but later underwent an uncomplicated total thyroidectomy at 35 weeks of gestation because of patient choice coupled with worsening thyrotoxicosis. CONCLUSION: In circumstances in which thionamides are contraindicated, management options of hyperthyroidism in pregnancy are limited. The proximity to term in the third trimester makes expectant management an attractive approach when maternal thyroid indices are stable, allowing for a choice of postpartum therapies without the worry of fetal implications. However, this strategy carries risks, and thyroidectomy in the third trimester can be a safe alternative.

The past, present, and future of selective progesterone receptor modulators in the management of uterine fibroids

Uterine fibroids are common in women of reproductive age and can have a significant impact on quality of life and fertility. Although a number of international obstetrics/gynecology societies have issued evidence-based clinical practice guidelines for the management of symptomatic uterine fibroids, many of these guidelines do not yet reflect the most recent clinical evidence and approved indication for one of the key medical management options: the selective progesterone receptor modulator class. This article aims to share the clinical experience gained with selective progesterone receptor modulators in Europe and Canada by reviewing the historical development of selective progesterone receptor modulators, current best practices for selective progesterone receptor modulator use based on available data, and potential future uses for selective progesterone receptor modulators in uterine fibroids and other gynecologic conditions.

Options to Evaluate Ureter Patency at Cystoscopy in a World Without Indigo Carmine

Intraoperative cystoscopy has been studied as a means to identify ureteral injuries at the time of gynecologic surgery. The majority of published studies investigating intraoperative cystoscopy have used indigo carmine to dye the urine to allow visualization of ureteral jets; unfortunately, however, this dye is currently not available in North America. The unavailability of indigo carmine may be a permanent reality that forces gynecologists to examine alternatives for the evaluation of ureteral integrity. Various alternative methods have been suggested, ranging from cystoscopy without dye to other commercially available products that dye the urine. Alternatives to cystoscopy for assessing ureteral integrity exist as well. This review provides an evidence-based review of the various methods available for evaluating ureteral patency, with specific information on dosing, adverse effects, and contraindications. This review will equip practicing gynecologists to choose an alternative method for assessing ureteral integrity that is tailored to their specific needs.