Evolution of a chronic pain management program in a Northwestern Ontario community: from structural elements to practical application.

BACKGROUND: Chronic pain is a highly prevalent health problem especially in rural regions. There is a dearth of comprehensive pain management programs particularly in rural areas. AIM: The objectives of this paper are to describe the evolution of an interprofessional chronic pain team employing a patient-centered model of care with a biopsychosocial approach, and health services metrics. METHOD: This descriptive case study approach includes an overview of the Chronic Pain Management Program (CPMP) services at St. Joseph Care Group in Thunder Bay, NW Ontario; the process involved in the development of an interprofessional chronic pain team employing a patient-centered model of care with a biopsychosocial approach; and metrics of the program's operations. RESULTS: Established in 1998, CPMP has evolved to become inter-professional, providing consultations and management, with partial funding by the Ontario Ministry of Health and Long term Care that has allowed expansion of services. The CPMP currently provides three distinct program streams as follows: a) Intensive 6-week, four half-days/week, outpatient program that offers an interdisciplinary team approach in groups and individual format; b) PACE-IT (Pain Assessment Collaborative Education Inter-professional Therapy), 8-week long, half-day/ week, interprofessional treatment program, in person; and c) Individual format for one-on-one services for patients not fitting in either the 6-Week or PACE-IT programs. In addition, Additional services provide virtual consultations and didactic videoteleconference sessions on opioid stewardship and pain management to health providers. Health services outcomes, research, and educational opportunities across the Northwestern Ontario Region, challenges and future needs are discussed. CONCLUSION: The CPMP's model of care can serve as a foundation for expert chronic pain care delivery across rural Canada, and as template for similar institutionally-based and publicly funded pain clinics.

Practice Paradigms Before and After Introduction of the Diagnosis-Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP): an Institutional Experience.

The recently adopted terminology of "Noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) reflects the indolent behavior of these tumors. In contrast to conventional papillary thyroid carcinomas, NIFTP can be managed conservatively. The purpose of this study was to investigate changes in surgical and pathologic practice patterns at our institution since the introduction of the NIFTP diagnosis in 2016. A retrospective analysis of all thyroid specimens received in our laboratory between January 2015 and April 2017 was performed. The final cohort consisted of 1508 thyroidectomy specimens from 1508 patients (1153 (76.5%) women and 355 (23.5%) men), of which 1011 (67%) were total thyroidectomies and 497 (33%) were partial thyroidectomies. There were 558 (69.2%) total thyroidectomies and 248 (30.8%) partial thyroidectomies performed prior to introduction of the NIFTP diagnosis and 453 (64.5%) and 249 (35.5%) total and partial thyroidectomies, respectively, after the change in nomenclature. Within a year following the initial use of this diagnosis, 67 NIFTP cases were identified (9.5% of all thyroidectomies), whereas compared with the year preceding it, malignant diagnoses decreased from 54.5 (439) to 44.6% (313), and the benign category remained unchanged from 44.5 (367) to 45.9% (322). For the entirely submitted 67 NIFTP cases, the mean number of blocks submitted was 14.7 (0.98 blocks/g); for malignant lesions 17.7 (0.92 blocks/g); and for benign lesions 16.6 (0.75 blocks/g). The results of our study suggest that NIFTP are encountered in almost 10% of thyroidectomies at our institution with expected shifts in cytology and surgical pathology diagnoses as a result of the change in nomenclature. During this time period, significant shifts towards less aggressive surgical management were not observed. All 67 NIFTP nodules were submitted entirely with no significant difference in the number of cassettes submitted for NIFTP nodules as compared with follicular variant papillary thyroid carcinoma (PTC), classic variant PTC, or follicular adenoma.

Role of Ancillary Techniques in Cervical Biopsy and Endocervical Curettage Specimens as Follow-Up to Papanicolaou Test Results Indicating a Diagnosis of Atypical Squamous Cells, Cannot Exclude High-Grade Squamous Intraepithelial Lesion, or High-Grade Squamous Intraepithelial Lesion.

The Papanicolaou (PAP) test is widely used to screen for cervical cancer. All high-grade lesions such as atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H), and high-grade squamous intraepithelial lesion, identified on a PAP test should be followed-up by a confirmatory cervical biopsy. In this review, we discuss the challenges in interpreting cervical tissue specimens and the various ancillary techniques used in the evaluation of cervical dysplasia. Ancillary studies include deeper levels, p16 immunohistochemistry (IHC), human papillomavirus (HPV) testing, and, importantly, cyto-histologic correlation. Of these, p16 IHC is consistently sensitive and specific for detecting HSIL. HPV RNA in situ hybridization (ISH) is a newer technique with excellent sensitivity and specificity for detecting virally infected cells and it may be more broadly applicable to both low- and high-grade squamous intraepithelial lesions.

High-dose chemotherapy and stem-cell rescue for salvage therapy for relapsed malignant mixed ovarian germ cell tumor: A case report.

BACKGROUND: Malignant ovarian germ cell tumors are rare, and often treatable with surgery and chemotherapy. Few data are available for treatment of platinum-resistant tumors. CASE: A 31 year old gravida 0 with a 20 cm pelvic mass was found to have a malignant ovarian germ cell tumor after she underwent debulking surgery. She initially responded to chemotherapy; however her AFP began to rise before all cycles were completed. She underwent additional debulking surgery that was again suboptimal. She was then referred for salvage therapy with high-dose chemotherapy with stem cell transplant, which was successful and she has had no evidence of disease for over two years. CONCLUSION: High-dose chemotherapy with stem cell transplant is a viable salvage therapy for patients with platinum-resistant germ cell tumors.

A comprehensive musculoskeletal and peripheral nervous system assessment of war-related bilateral upper extremity amputees.

BACKGROUND: Upper limb amputations are one of the unpleasant war injuries that armed forces are exposed to frequently. The present study aimed to assess the musculoskeletal and peripheral nervous systems in Iraq-Iran war veterans with bilateral upper extremity amputation. METHODS: The study consisted of taking a history and clinical examinations including demographic data, presence and location of pain, level of amputation, passive and active ranges of movement of the joints across the upper and lower extremities and spine, manual palpation, neurological examination, blood circulation pulses and issues related to a prosthetic limb. In this study, 103 Iranian bilateral upper extremity amputees (206 amputations) from the Iran-Iraq war were evaluated, and a detailed questionnaire was also administered. RESULTS: The most common level of amputation was the finger or wrist level (108, 52.4 %). Based on clinical examination, we found high frequencies of limited active and passive joint range of movement across the scapula, shoulder, elbow, wrist and metacarpophalangeal, interphalangeal and thumb joints. Based on muscle strength testing, we found varying degrees of weakness across the upper limbs. Musculoskeletal disorders included epicondylitis (65, 31.6 %), rotator cuff injury (24, 11.7 %), bicipital tendonitis (69, 33.5 %), shoulder drop (42, 20.4 %) and muscle atrophy (19, 9.2 %). Peripheral nerve disorders included carpal tunnel syndrome in 13 (6.3 %) and unilateral brachial plexus injury in 1 (1 %). Fifty-three (51.5 %) were diagnosed with facet joint syndrome at the level of the cervical spine (the most frequent site). Using a prosthesis was reported by 65 (63.1 %), both left and right sides. The back was the most common site of pain (71.8 %). CONCLUSION: The high prevalence of neuro-musculoskeletal disorders among bilateral upper extremity amputees indicates that they need regular rehabilitation care.

High-level expression of divergent endodermal lineage markers in gonadal and extra-gonadal yolk sac tumors.

Yolk sac tumors occur at both gonadal and extra-gonadal sites. A recent case of ovarian endometrioid-pattern yolk sac tumor with strong diffuse expression of TTF-1 illustrated the potential for misdiagnosis due to divergent expression of endodermal lineage markers. The aim of this study was to investigate the expression of four divergent endodermal lineage markers, TTF-1, CDX2, Hep Par 1, and Napsin A, in gonadal and extra-gonadal yolk sac tumors of differing age, sex, and location (excluding foci of overt hepatoid differentiation). We identified 26 cases (5 ovarian, 15 testicular, and 6 extra-gonadal) containing yolk sac tumor as identified by typical histology and confirmed by positive immunohistochemical staining for alpha-fetoprotein and glypican-3. Mixed or ambiguous foci were confirmed by immunohistochemistry (SALL4 positive and Oct-4 negative). The relative proportion of three histologic patterns: reticular/cystic, solid/myxoid, and glandular was estimated. Percent positivity for the four divergent endodermal lineage markers was compared within yolk sac tumor areas according to site, age group, and histologic pattern. High-level (>25%) staining for one or more divergent endodermal lineage markers was seen in eleven cases: Hep Par 1 in seven cases, all post-pubertal, TTF-1 in four cases, two ovarian and two extra-gonadal, and CDX2 in three cases, with no age or site predilection. No case highly expressed all three divergent endodermal lineage markers, but four co-expressed high levels of two markers: two ovarian yolk sac tumors with TTF-1 and Hep Par 1, one testicular yolk sac tumor with CDX2 and Hep Par 1, and one extra-gonadal yolk sac tumors with TTF-1 and CDX2. While no absolute correlation of high-level divergent endodermal lineage marker expression with histologic subtype was observed, TTF-1 and CDX2 expression was predominantly seen in reticular/cystic and glandular areas while Hep Par 1 was most frequent in myxoid/solid and glandular areas.

MUC16 (CA125): tumor biomarker to cancer therapy, a work in progress.

Over three decades have passed since the first report on the expression of CA125 by ovarian tumors. Since that time our understanding of ovarian cancer biology has changed significantly to the point that these tumors are now classified based on molecular phenotype and not purely on histological attributes. However, CA125 continues to be, with the recent exception of HE4, the only clinically reliable diagnostic marker for ovarian cancer. Many large-scale clinical trials have been conducted or are underway to determine potential use of serum CA125 levels as a screening modality or to distinguish between benign and malignant pelvic masses. CA125 is a peptide epitope of a 3-5 million Da mucin, MUC16. Here we provide an in-depth review of the literature to highlight the importance of CA125 as a prognostic and diagnostic marker for ovarian cancer. We focus on the increasing body of literature describing the biological role of MUC16 in the progression and metastasis of ovarian tumors. Finally, we consider previous and on-going efforts to develop therapeutic approaches to eradicate ovarian tumors by targeting MUC16. Even though CA125 is a crucial marker for ovarian cancer, the exact structural definition of this antigen continues to be elusive. The importance of MUC16/CA125 in the diagnosis, progression and therapy of ovarian cancer warrants the need for in-depth research on the biochemistry and biology of this mucin. A renewed focus on MUC16 is likely to culminate in novel and more efficient strategies for the detection and treatment of ovarian cancer.

Clinical response to a second uterine curettage in patients with low-risk gestational trophoblastic disease: a pilot study.

OBJECTIVE: To determine the curative effect of a repeat uterine evacuation in patients with low-risk gestational trophoblastic neoplasia. STUDY DESIGN: Patients with low-risk gestational trophoblastic neoplasia (GTN)(N=12), diagnosed according to the International Federation of Gynecology and Obstetrics 2002 guidelines, were enrolled in a prospective cohort study. Primary outcomes were need for chemotherapy after second uterine evacuation and number of chemotherapy courses needed to achieve complete remission. RESULTS: Ten patients (83%) did not require chemotherapy and were cured bya second curettage. Two patients failed to respond to the second curettage and received single-agent chemotherapy with actinomycin-D (1.25 mg/m2 biweekly, slow intravenous administration). Both patients responded to chemotherapy as second-line therapy. A 100% remission rate was achieved, with no recurrence at the 1-year follow-up. One patient (8%) had a uterine perforation. CONCLUSION: Second curettage has a favorable response rate. It seems reasonable to perform a second curettage in patients with low-risk GTN in settings where serum beta-hCG assay follow-up is highly reliable and available. However, its potential complications and inconvenience must be discussed critically with each patient.

Acceptable predictive accuracy of histopathology results by colposcopy done by Gynecology residents using Reid index.

OBJECTIVE: The aim of this study was to determine the strength of the correlation between colposcopic impression according to Reid colposcopic index (RCI) done by Gynecology residents and biopsy histology in a university hospital. METHODS: Colposcopy was performed on 260 women. According to RCI, the scores zero, one, or two were given to each of four standardized colposcopy patterns (acid staining, iodide staining, margin of lesion, and vascular pattern) and the total score was calculated. In those with multiple lesions, the patterns with the highest score were considered. Then the biopsy was obtained from the lesion and put in formalin for pathological evaluation. RESULTS: There was a statistically significant association between colposcopy findings and histopathology findings and the score was increased as parallel as malignancy grade (r = 0.680, P < 0.05). The highest sensitivity and specificity for diagnosis of each CIN also were related to staining with acetic acid. For high-grade CIN lesions, the highest specificity was related to staining with acetic acid, but the sensitivity was equal for four findings. CONCLUSION: Colposcopy using RCI yields a good correlation with histology results. It also showed that colposcopy done by Gynecology residents using RCI is a feasible and acceptable cervical cancer screening method in a university hospital.

Comparison of pulsed actinomycin D versus 5-day methotrexate for the treatment of low-risk gestational trophoblastic disease.

OBJECTIVE: To determine the effectiveness of 2 standard chemotherapy regimens for low-risk gestational trophoblastic disease according to the International Federation of Gynecology and Obstetrics (FIGO) staging system. METHODS: From 2008 until 2010, 75 women with low-risk gestational trophoblastic disease received either pulsed actinomycin D (n=50) or 5-day methotrexate (n=25). The primary remission rate, the duration of treatment, the number of treatment courses, and the adverse effects were compared. RESULTS: The complete remission rates were 90% for the actinomycin D group and 68% for the methotrexate group (P=0.018). The mean number of chemotherapy courses administered to achieve complete remission (including courses of second-line therapy) was 3.1 in the methotrexate group and 5.3 in the actinomycin D group (P=0.01). No major adverse effects were experienced in either treatment group and there were no significant differences in terms of adverse effects. Second-line chemotherapy was indicated for 11 patients. CONCLUSION: Based on the present study, pulsed actinomycin D seems to be an appropriate first-line treatment for patients with low-risk gestational trophoblastic disease.

Pregnancy outcome in patients with stage 1a endometrial adenocarcinoma, who conservatively treated with megestrol acetate.

OBJECTIVE: The most effective treatment of well-differentiated endometrial carcinoma is surgery. The aim of this study is the evaluation of megestrol acetate on young patients with well-differentiated endometrial cancer who wish to preserve their fertility, with regard to the receptors. METHODS: 16 patients were treated initially with 160 mg/d of megestrol acetate and continued with 320 mg/d for non-responsive cases. All patients followed with FD&C and hysteroscopy. The responsive patients were referred to IVF group. RESULTS: Response rate to hormonal therapy was 10/16 (62.5%). The mean time of responding was 7.5 months. Other six (37.5%) patients underwent total abdominal hysterectomy (TAH). Of 10 patients who responded to hormonal therapy, one exited of the study because of her husband's infertility. Two patients are under IVF. Three patients did not get pregnant and four patients became pregnant and finally underwent TAH. All patients had progesterone receptors. Only one patient lacked estrogen receptors; who also responded to treatment. CONCLUSION: Progestins treatment of these patients who want to have child may be useful, but close long-term follow-up is necessary. The evaluation of estrogen and progesterone receptors assay may be useful in predicting response to the treatment.

Potential diagnostic value of P16 expression in premalignant and malignant cervical lesions.

BACKGROUND: The goal of this study was to evaluate the results of the expression of p16INK4a in normal uterine cervical epithelium, low-grade cervical intraepithelial neoplasia (CIN), high-grade CIN, squamous cell carcinoma (SCC), and adenocarcinoma of the cervix, in order to help draw a distinction between low risk and high risk patients with cervical lesions. MATERIALS AND METHODS: [corrected] P16INK4a expression was evaluated by immunohistochemistry in 78 paraffin-embedded tissue samples including 39 normal cervical tissues, 11 low-grade CINs, 11 high-grade CINs, 22 cervical SCCs and 8 cervical adenocarcinomas. Two parameters in immunohistochemical p16 expression were evaluated: percentage of p16-positive cells, and reaction intensity. RESULTS: The p16INK4a expression rate was 81.8% in low-grade CINs, 91% in high-grade CINs, 90% in SCCs and 75% in cervical adenocarcinomas. 10% of normal cervical samples expressed p16. Moreover, there was a significant relationship between the histological diagnoses and percentage of positive cells and reaction intensity of p16 (p < 0.005). The intensity of the reaction was the best parameter to evaluate the positivity of p16. CONCLUSIONS: Over-expression of the p16INK4a was typical for dysplastic and neoplastic epithelia of the uterine cervix. However, p16INK4a-negative CINs and carcinomas did exist. Although negative p16INK4a expression does not definitely exclude the patient with cervical lesion from the high-risk group, immunohistochemical study for p16INK4a may be used as a supplementary test for an early diagnosis of cervical cancers.

Conservative management of placenta increta: case report and literature review.

Placenta increta, a rare complication of pregnancy, is associated with significant postpartum hemorrhage often requiring emergency hysterectomy. We report a case of conservative management, with a combination of parenteral methotrexate, serial ultrasound and ß-hCG assessment. Serum ß-hCG levels were undetectable after 8 weeks of therapy. A scan at 6 months showed complete involution of the uterus. Review of the literature discussing the diagnostic tools, clinical features, management and outcome of pregnancies with placenta increta.

The Persian version of locomotor capabilities index: translation, reliability and validity in individuals with lower limb amputation.

PURPOSE: To translate the Locomotor Capabilities Index (LCI-5) to Persian and to assess its psychometric properties when applied to a sample of people with lower limb amputation (LLA). METHODS: The LCI-5 was administered to 106 Persian speaking people with LLA to determine its internal consistency, item-subscale correlation, test-retest reliability and floor and ceiling effects. To assess the construct validity, each participant's performance was measured using the Timed Up and Go (TUG) and 2-Minute Walk Test. RESULTS: Minimum Cronbach's alpha of 0.70 was exceeded by LCI-5 subscales. Item-subscale correlations after correction for overlap were higher than the cuff-off point of 0.40. The intraclass correlation coefficient was 0.96 for LCI-5 total index in test-retest reliability. LCI-5 showed significant correlation with TUG (r = -0.65, P < 0.01) and 2-Minute Walk Test (r = 0.71, P < 0.01). The LCI-5 mean scores were higher for individuals with unilateral below-knee amputation than participants with above-knee amputation (t = 2.71, P = 0.008) and for individuals with unilateral amputation who do not use walking aids than those who use (t = -4.27, P < 0.01). Floor effect was found for none of the patients with LLA while ceiling effect was reported for 23.6% of patients. CONCLUSIONS: The Persian version of LCI-5 has acceptable levels of internal consistency, item-subscale correlation, test-retest reliability and construct validity. To detect intervention effects, the LCI-5 should be used cautiously in population of physically active and young patients with LLA due to its high ceiling effects.

Diagnostic accuracy of dilatation and curettage for abnormal uterine bleeding.

AIM: The objective of this study was to compare the histological findings of dilatation and curettage (D&C) with those on subsequent hysterectomy in patients with abnormal uterine bleeding. METHODS: Between October 1998 and September 2003 a retrospective clinical study of 311 patients was conducted, including all patients who underwent D&C and within 2 months, hysterectomy because of histological findings on D&C or persistence of symptoms. The sensitivity, specificity, positive and negative predictive value and accuracy of D&C were studied. RESULTS: The mean age of our patients was 46.6 years. In 164 of 311 patients (52.7%), D&C failed to detect intrauterine disorders subsequently found at hysterectomy. The sensitivity was 30.2%, the specificity was 72.3%, the positive predictive value was 77.1%, and the negative predictive value was 25.1%. The accuracy was 40.5% overall. CONCLUSION: D&C is an inadequate diagnostic tool for uterine focal lesions, but the accuracy of D&C in the detection of endometrial hyperplasia and carcinoma is relatively high (92.1%).

Chronic pain after spinal cord injury: results of a long-term study.

OBJECTIVE: Chronic pain after spinal cord injury (SCI) is a common and considerable complication and may continue for a long time. DESIGN: During a 2-year survey, 13.9 +/- 3.0 years after injury, a total of 1,295 war-related spinal cord injury survivors were thoroughly examined by physical and rehabilitation specialists and all relevant data, consisting of type and site of pain as well as exacerbating or palliative factors, were recorded. PATIENTS: The mean age of the survivors was 35.9 +/- 7.2; 98.5% were male and 1.5% were female. The level of injury was cervical in 9.3%, thoracic in 67%, and lumbosacral in 23.7%, with 8.1% tetraplegic and 89.1% paraplegic. About 89.8% had complete spinal cord injuries and 10.2% had incomplete spinal cord injuries, based on sensory and motor testing. RESULTS: Spinal cord related pain was reported in 64.9% of the subjects; 8.8% reported a history of pain but had no complaint at the time of examination, and 26.3% had never suffered from any pain. Patients suffering from lumbar spinal cord injury reported the highest percent of pain perception, with pain detected in 83.5% of these patients. Common sites of reported pain were the distal lower extremities (46.5%), proximal lower extremities (40.9%), pelvic girdle (24.5%), and upper limbs (5.7%). CONCLUSION: Spinal cord injury-related pain interferes with daily activities of patients and significantly influences their quality of life.

Phantom pain in bilateral upper limb amputation.

PURPOSE: To alert health professionals on presence and extent of phantom pain and sensation following bilateral upper limb amputation. METHODS: Of a total of 140 war-related bilateral upper limb amputees in Iran, 103 subjects were thoroughly examined in this cross-sectional study by a physical medicine specialist. The patients were questioned for the presence of phantom pain and sensations, and frequency and intensity of the feeling were recorded. RESULTS: At 17.1 +/- 6.1 years after injury, 82.0% of the 103 amputees suffered from phantom sensation, including varying degrees of phantom limb pain in 53.9% of stumps. Phantom phenomena had a higher frequency in the right extremities, but this was not statistically significant (p > 0.01). Of those amputees who had phantom pain or sensation, 51.2% reported that they 'always' had phantom limb sensation; and approximately one-fourth of the subjects (24.6%) 'always' had phantom pain. Among the stumps who reported phantom pain (N=112), the pain was excruciating (38.5%), distressing (34.9%) or discomforting (25.6%). A significant statistical relation between phantom limb sensation and level of amputation was observed (p < 0.01). CONCLUSION: At this time there is no healing for phantom pain; medical and surgical modalities only bring temporary relief, and less than 1% of the respondents achieve permanent relief through different treatment methods.

Comparison of three management strategies for patients with atypical squamous cells of undetermined significance, after six months delay: a three-year experience in an Iranian university hospital.

BACKGROUND: A Pap test result of atypical squamous cells of undetermined significance (ASCUS) presents a clinical challenge. Only 5-10% of women with ASCUS harbour serious cervical disease. METHODS: We screened 3619 women, who attended to Mirza Koochak Khan Hospital at Tehran University of Medical Sciences with Pap smears, of whom 100 returned with ASCUS. After six months, each subject underwent a standard cytology (conventional Pap smear), human papillomavirus (HPV) DNA testing (identifying high-risk HPV types with polymerase chain reaction) and colposcopy with multiple cervical biopsies. RESULTS: Mean age was 44.09 +/- 8.6 years. The estimated prevalence of cervical intraepithelial neoplasia (CIN) II or higher was 4%. When histologically verified high-grade lesions (> or = CIN II) were observed, the relative sensitivity of HPV DNA testing was 100% compared with conventional Pap smear, which performed 75% versus 100% relative sensitivity, respectively, using cytological diagnosis high-grade squamous intraepithelial lesion, or low-grade squamous intraepithelial lesion (LSIL) as the cut-off. Negative and positive predictive values (NPV and PPV) of Pap test were 98.9% and 100%. The NPV and PPV of HPV DNA testing were 100%. CONCLUSIONS: Although less complicated than colposcopy, the repeat Pap smear triage algorithm for ASCUS may underdiagnose some women with high-grade CIN, when compared with colposcopy. Considering the high sensitivity of HPV testing, it may be useful as an alternative to the current policy of six-month repeat cytology for women with ASCUS results.

Efficacy of megestrol acetate (megace) in the treatment of patients with early endometrial adenocarcinoma: our experiences with 21 patients.

BACKGROUND: There are therapeutic dilemmas regarding fertility-preserving treatment among young women with well-differentiated endometrial carcinoma. MATERIALS AND METHODS: Twenty-one patients with stage IA well-differentiated endometrial adenocarcinoma were enrolled in a prospective study. The treatment initiated with 160 mg/d of megestrol acetate. The patients underwent dilatation and curettage and hysteroscopy after 3 months, and in cases of normal pathology, the therapy continued for another 3-month period. In patients who did not respond to treatment, the dosage of the drug was doubled (320 mg/d), and the therapy continued for another 3 months. At the second time, patients who did not respond to treatment were recommended for hysterectomy, and in patients who responded to treatment, an additional 3 months of treatment with megestrol acetate (320 mg/d) was administered. RESULTS: Our results showed a response rate of 85.71% (18 patients), and 3 patients underwent hysterectomy. The mean (SD) treatment duration was 8.85 (2.00) months (range, 6-12 months). The response to therapy was observed in 5 patients (27.78%) with a dosage of 160 mg/d, and the remaining patients with 320 mg/d. Pregnancy occurred in 5 patients (27.78%). Recurrence happened in 3 (16.67%) of 18 patients who responded to treatment who did not give a permit to undergo hysterectomy and received medication again. Two (66.67%) of these patients experienced remission again, whereas the other one was candidate for hysterectomy. CONCLUSIONS: The results of this study show that, when an initial response is not achieved or when disease recurs, use of 320 mg/d seems to be associated with a better therapeutic response. Furthermore, serious complications were not observed with this dosage.