Levonorgestrel-releasing intrauterine device in the treatment of abnormal uterine bleeding: a 6- and 12-month morphological and clinical follow-up.

BACKGROUND: Abnormal uterine bleeding is defined as any alteration in the pattern or volume of menstrual blood flow, and it is preferably treated using hysterectomy, endometrial destruction or the levonorgestrel-releasing intrauterine system (Mirena(®) ). Recently, it has been demonstrated that studies of Mirena(®) were generally small and consequently imprecise. AIMS: Our study was aimed at assessing the effects of a slow-release levonorgestrel (20 µg/day) intrauterine device in fertile and postmenopausal women experiencing abnormal uterine bleeding that did not respond to traditional medical management. MATERIALS AND METHODS: A total of 40 women, of whom 24 were of reproductive capacity and 16 were postmenopausal, were enrolled in the trial. Removal of the intrauterine device was required for only 2 of the 24 fertile women and for only 3 of the 16 postmenopausal women. After 6 and 12 months of treatment, the remaining women were clinically evaluated and underwent ultrasound and hysteroscopy using biopsy specimens as a control. The EuroQol Group EQ-5D questionnaire was used for evaluation of quality of life. RESULTS: The device showed good tolerability and efficacy. It resulted in a reduction in the endometrial mucosal thickness with a regression of bleeding and collateral effects, which were more evident after 12 months of treatment. A positive effect of the device on the woman's quality of life was demonstrated. CONCLUSIONS: The slow-release levonorgestrel intrauterine device may be a valid therapeutic tool for treating basic symptomatology and increasing quality of life in women with abnormal uterine bleeding.

Morphological study of the residual ovarian tissue removed by laparoscopy or laparotomy in adolescents with benign ovarian cysts.

BACKGROUND/PURPOSE: The stripping of benign ovarian cysts has been reported to be preferable to cyst wall ablation. The procedure can be performed via either an open or laparoscopic approach. The aim of our study was to evaluate the efficacy of the technique of stripping performed by laparoscopy and laparotomy in the treatment of benign ovarian masses in the pediatric age group with respect to healthy ovarian tissue. METHODS: This retrospective study evaluated all the pediatric or adolescent patients admitted during a 5-year period (2006-2010) for a suspected benign ovarian cyst treated with a laparoscopic technique or traditional open surgery to remove the cyst. The morphological characteristics of the tissue were graded on a semiquantitative scale from 0 to 4. RESULTS: Thirty patients were treated and divided in 2 groups: group A laparoscopy (18 patients) and group B open (12 patients). The median age was 9.1 years. No ovarian tissue could be observed in 26 cases (86.7%). In the 4 remaining (2 laparoscopic and 2 open) cases (13.3%), ovarian tissue was found, but never more than 1 mm in thickness. This finding was always in endometriotic cysts. CONCLUSIONS: We demonstrated that, in the pediatric population, no ovarian tissue is removed together with the cyst if this is nonendometriotic. The type of surgical procedure does not influence the removal of ovarian tissue. Laparoscopic stripping of ovarian cysts is the preferable surgical procedure in patients with prospective potential fertility because of their young age.

Delayed delivery of a twin pregnancy and uterine atony: morphological and clinical evidence.

This report presents the uncommon case of a 154-day delayed delivery in a spontaneous twin pregnancy associated with uterine atony. After abortion of the first fetus at 16 weeks, a healthy male was born at 38 weeks. Postpartum hemorrhage due to uterine atony, which was successfully treated with prostaglandins, occurred.

Efficacy of laparoscopic stripping for ovarian cysts: histological and clinical findings.

AIM: The aim of our study was to evaluate the efficacy of the laparoscopic stripping technique on benign ovarian masses with respect to healthy ovarian tissue. MATERIAL AND METHODS: Seventy-six patients between 14 and 40 years of age were enrolled after receiving a diagnosis of mono-lateral ovarian cyst and underwent laparoscopic surgery for cyst excision with the stripping technique. Histological observations of these specimens were then performed and graded on a semiquantitative scale. RESULTS: The 76 samples included 36 endometriotic cysts, 18 dermoid cysts, 12 serous cysts, and 10 mucinous cysts. Only 26 of the endometriomas showed histological evidence of healthy ovarian tissue that, however, differed morphologically from normal ovarian tissue. CONCLUSION: The laparoscopic stripping technique used for the excision of different ovarian cysts is a practice that safeguards the organ.

Genistein aglycone: a new therapeutic approach to reduce endometrial hyperplasia.

OBJECTIVE: Endometrial hyperplasia without cytological atypia is commonly treated with progestins, but other treatment regimes may be available with equivalent efficacy and low side effects. DESIGN: A randomized double-blind, placebo and progesterone-controlled clinical trial to evaluate the effects of genistein aglycone in reducing endometrial hyperplasia. PATIENTS: A group of 56 premenopausal women with non-atypical endometrial hyperplasia were enrolled and received: genistein aglycone (n=19; 54 mg/day); norethisterone acetate (n=19; 10 mg/day on days 16-25 of the menstrual cycle) or placebo (n=18) for 6 months. MEASUREMENTS: Hysteroscopy was performed with biopsies and symptomology assessed at baseline, 3 and 6 months of administration. The effect on estrogen (ER) and progesterone receptors (PR) expression in uterine biopsies were assessed after 3 and 6 months. For each treatment follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), sex hormone-binding globulin (SHBG) and progesterone (PG) levels were also evaluated. RESULTS: After 6 months, 42% of genistein aglycone-administered subjects had a significant improvement of symptoms (histologically confirmed in the 29%) compared to 47% of norethisterone acetate subjects (histologically confirmed in the 31%), but only 12% in the placebo group with 19% exhibiting worsening symptoms and increased endometrial thickness. No significant differences were noted for hormone levels for any treatment, but immunohistochemical analysis revealed significantly reduced staining for ER-alpha and PR and enhanced ER-beta1 staining in genistein-administered subjects associated with a complete regression of bleeding. CONCLUSIONS: These results suggest that genistein aglycone might be useful for the management of endometrial hyperplasia without atypia in women that cannot be treated with progestin.

Molecular events involved in the morphogenesis of multicystic dysplastic kidney.

INTRODUCTION: Wnt-1 is capable of inducing metanephric mesenchyme to undergo tubulogenesis. A relationship between the degree of cystogenesis and reduced E-cadherin (E-cad) expression was described. Syndecan-1 (Sdc-1) has a critical role in kidney development. MATERIALS AND METHODS: Ten multicystic dysplastic kidneys (MCDKs) were stained with hematoxylin and eosin and immunohistochemistry was performed using Wnt-1, E-cad and Sdc-1 antibodies. Eight unaffected kidneys were used as controls. RESULTS: Strong Wnt-1 immunostaining occurred inside cystic/tubular epithelial cells and in blastematous foci. An immunoreaction was observed in glomerular epithelial cells. In controls, just weak cytoplasmic Wnt-1 positivity was seen in tubular epithelial cells. E-cad reaction was negative in MCDKs while strong immunostaining was common in tubular cells of controls. A strong Sdc-1 immunoreaction depicted cystic, tubular and glomerular epithelial cells in MCDKs while Sdc-1 expression documented weak positivity in tubular epithelium alone. CONCLUSIONS: Our data are in accordance with an involvement of Wnt-1 in normal nephrogenesis and with its role in altered epithelial differentiation of metanephric mesenchyme in MCDKs. Wnt-1 signal may function to suppress E-cad expression, a predisposing event for cystogenesis. High expression of Sdc-1 in tubular/cystic epithelial cells of MCDKs might alter the normal transition of stages of the developmental process and modify the anion charge of the glomerular barrier.

Intramural ganglion structures in esophageal atresia: a morphologic and immunohistochemical study.

Introduction and Aim. Disorders of esophageal motility causing dysphagia and gastroesophageal reflux are frequent in survivors to esophageal atresia (EA) and distal tracheoesophageal fistula (TEF). The aim of the present study was to investigate the histologic and immunohistochemical features in both esophageal atretic segments to further understand the nature of the motor disorders observed in these patients. Material and Methods. Esophageal specimens from 12 newborns with EA/TEF and 5 newborns dead of unrelated causes were examined. The specimens were fixed in 5% buffered formalin, included in paraffin and cut in 5 micron sections that were stained with hematoxilin and eosin (H and E), and immunohistochemical stainings for Actin, S-100 protein, Neurofilament, Neuron-Specific-Enolase, Chromogranin A and Peripherin were evaluated under the microscope. Results. In controls, the distribution of the neural elements was rather homogenous at both levels of the esophagus. In contrast, the atretic segments showed quantitative and qualitative differences between them with sparser nervous tissue in the distal one in comparison with the proximal one and with controls. Conclusions. These results further support the assumption that histomorphological alterations of the muscular and nervous elements within the esophageal wall might contribute to esophageal dysmotility in patients surviving neonatal operations for EA/TEF.

Dextranomer/hyaluronic Acid copolymer implant for vesicoureteral reflux: role of myofibroblast differentiation.

PURPOSE: Dextranomer/hyaluronic acid implantation is associated with a granulomatous inflammatory reaction, replaced by fibrosis. Appearance of myofibroblasts is considered a crucial event in fibrosis, and CD68 positive cells and other factors are implied in their activation. Mast cells are a source of these factors and tryptase can induce fibroblast to express alpha-smooth muscle actin, which is characteristic of myofibroblasts. We evaluated histological changes in refluxing ureters treated with dextranomer/hyaluronic acid and immunolocalized CD68 positive cells, tryptase mast cells and myofibroblasts. MATERIALS AND METHODS: We performed histological, histochemical and immunohistochemical analyses in 22 refluxing ureters treated with dextranomer/hyaluronic acid in comparison with 17 refluxing ureters who underwent ureteral reimplantation but did not receive endoscopic bulking agent. We used CD68 antibody for monocytes/macrophages and epithelioid cells, mast cell tryptase mouse antibody for mast cells, and alpha-smooth muscle actin and vimentin antibodies for myofibroblasts. The area of the ureteral lumen in dextranomer/hyaluronic acid treated and untreated ureteral endings was measured. RESULTS: Sirius red documented a major grade of histological lesions in dextranomer/hyaluronic acid treated refluxing ureters. CD68 and tryptase mast cell staining showed a significant enhancement of positive cells in dextranomer/hyaluronic acid treated refluxing ureters. Immunostaining for alpha-smooth muscle actin and vimentin displayed a myofibroblastic invasion in dextranomer/hyaluronic acid. Measurement of surface in treated refluxing ureters was significantly less than in untreated refluxing ureters. CONCLUSIONS: Our data documented a recruitment of CD68 and tryptase positive cells, abnormal accumulation of collagenous stroma and successive extracellular matrix remodeling through differentiation of myofibroblasts. Myofibroblasts might provoke tissue contraction, decreasing the ureteral diameter and modifying the ureteral length-to-diameter ratio, preventing urine reflux.

Is the stripping technique a tissue-sparing procedure in large simple ovarian cysts in children?

BACKGROUND: Stripping of the cystic wall is performed by gynecologists to treat large ovarian cysts. Information in the pediatric population is poor. We prospectively evaluated the pathologic specimens of large ovarian cyst to determine whether the stripping technique is a tissue-sparing procedure even in this age. METHODS: We evaluated 5 patients. Samples were taken from the intermediate part of the cystic wall and from the layer covering the cyst during excision. The presence of ovarian tissue adjacent to the cyst wall, and the morphological features of the surrounding tissue were both evaluated. Pelvic ultrasound follow-up was also performed. RESULTS: Patients' mean age was 4.5 years (7 days to 12 years). All cysts were removed because all were symptomatic. The mean diameter was 86.6 mm (74-100 mm). Cysts were follicular in 2 cases, serous in other two, and endometriotic in 1 case. Adjacent ovarian tissue was present in 1 of 5 specimens and was approximately 1 to 2 mm in thickness. The layer adjacent to the cystic wall always appeared as normal ovarian tissue. Ultrasound scans at follow-up revealed presence of ovarian tissue. CONCLUSION: The stripping procedure for large ovarian cyst excision allows to spare the adjacent normal ovarian tissue even in pediatric age because ovarian tissue is rarely excised with the cyst wall during the procedure.

Occult hepatitis B virus infection is associated with the development of hepatocellular carcinoma in chronic hepatitis C patients.

BACKGROUND: Occult hepatitis B virus (HBV) infection frequently occurs in patients with HBV surface antigen (HBsAg)-negative chronic liver disease, and much evidence suggests that it is a risk factor for hepatocellular carcinoma (HCC) development. However, to the authors' knowledge, no follow-up study has been performed to date evaluating HCC occurrence over time in chronic hepatitis patients with or without occult HBV infection. METHODS: A cohort of the 380 HBsAg-negative chronic hepatitis patients attending the study institution between 1991-2000 were evaluated and tested for occult HBV DNA by analysis of liver biopsy specimens. RESULTS: There were 135 patients (35.5%) with occult HBV and 245 patients (64.5%) without occult HBV. Cirrhosis was significantly associated with occult HBV infection (P = 0.01). One hundred thirty-four of these patients were followed for a minimum of 50 months (median, 82.8 +/- 32.6 mos). Fifty-three patients (39%) were occult HBV carriers and 81 (61%) were not. Nine patients developed HCC during the follow-up; eight were positive and one was negative for occult HBV (P = 0.002). CONCLUSIONS: The current observational cohort study showed that, among the HBsAg-negative patients with chronic hepatitis, HCC develops for the most part in carriers of occult HBV. Therefore, the evaluation of HBV genomes in chronic hepatitis patients appears to be a powerful tool for the identification of individuals at higher risk of HCC development.

Candesartan cilexetil-induced severe hepatotoxicity.

We report a case of severe hepatotoxicity associated with ductopenia in a 61-year-old woman. The patient developed jaundice, vomiting, and abdominal pain a few weeks after the beginning of treatment with candesartan cilexetil, 16 mg/d, for essential hypertension. Liver biopsy showed parenchymal bilirubinostasis with portal cholangitis and ductopenia. The drug was immediately withdrawn, and in the following weeks, aminotransferases and serum bilirubin returned to normal levels. The clinical-histologic data and the exclusion of known causes of liver disease led us to make a diagnosis of drug-induced cholestasis. To our knowledge, this is the first description of severe hepatotoxicity associated with ductopenia caused by an adverse reaction to candesartan cilexetil.