Reuvit Halperin

The Major Histopathologic Characteristics in the Vulvar Vestibulitis Syndrome

Objective: In order to better understand the etiology of the vulvar vestibulitis syndrome, we examined the histopathologic parameters in vestibular mucosa, and compared the findings in specimens obtained from women with vulvar vestibulitis with those obtained from the control group. Study Design: Specimens of vestibulitis were obtained from 24 patients, undergoing circumferential vestibulectomy under general anesthesia due to the symptoms and signs consistent with vulvar vestibulitis. Control specimens were obtained from 16 women, without symptoms or signs of vulvar vestibulitis, undergoing reconstructive introital surgery due to roomy vagina, rectocele or painful episiotomy. All vestibular tissue specimens were examined for intensity of inflammation, extension of inflammatory cells into the epithelium, vascular proliferation, the presence of mast cells and proliferation of peripheral nerve bundles. Results: No significant difference was found regarding the degree of inflammation, the extension of inflammatory cells into the epithelium, the vascular proliferation and the presence of mast cells while comparing the study and the control groups. The only histopathologic feature, differentiating the patients with vulvar vestibulitis from the control group, was the proliferation of peripheral nerve bundles found in 19 out of 24 (79.1%) specimens expressing vestibulitis and in none of 16 control specimens (p < 0.0001). Conclusion: Our results, therefore, support the existence of peripheral nerve hyperplasia in vestibular tissue obtained from patients with vulvar vestibulitis, and exclude the role of active inflammation or mast cells as probable etiologies for the vulvar vestibulitis syndrome.

Placental Apoptosis in Normal and Abnormal Pregnancies

The aim of this study was to demonstrate apoptosis in the human placenta in normal and abnormal pregnancies. The percentage of apoptotic cells in placental samples was quantified by analyzing the cell cycle of nuclei stained with propidium iodide using a flow cytometer. No significant difference in the percentage of apoptotic cells was obseved comparing the group of normal pregnancies (first and second trimesters) with those of missed abortions. There was also no difference in the incidence of apoptosis comparing placental samples obtained from chromosomally normal and abnormal pregnancies. Yet, there was a significant increase in the incidence of apoptosis in placental samples obtained from second and third trimesters as compared with those obtained from the first trimester (p < 0.04 and p < 0.01, respectively). There was also a significant increase in the incidence of placental apoptosis in the third as compared with the second trimester (p < 0.03).

Can we rely on blind endometrial biopsy for detection of focal intrauterine pathology

OBJECTIVE To compare the diagnostic power of random endometrial biopsy with hysteroscopy for intrauterine lesions. STUDY DESIGN A retrospective cohort study of 639 women evaluated by diagnostic office hysteroscopy and endometrial biopsy (Novak curette) was carried out between 10/1997-6/2000. Reasons for evaluation were postmenopausal bleeding, abnormal uterine bleeding, ultrasound or hystero-salpingography findings, intrauterine device removal, suspected retained products of conception, infertility, late abortions and recurrent abortions. RESULTS The womens mean age was 43.4+/-13.3 years (range, 18-88). The most prevalent indication for investigation was abnormal uterine bleeding (n=218, 34.1%), followed by sonographic or hystero-salpingographic findings (n=167, 26.1%). Hysteroscopy revealed a normal uterine cavity in 367 (57.4%) women. Endometrial polyps and submucosal fibroids were the most common hysteroscopic findings (in 151 [23.6%] and 72 [11.3%], respectively). The hysteroscopic findings were compared with the pathology results in 558 cases. The sensitivity of the Novak curette for detection of endometrial polyps and submucosal fibroids was only 8.4% and 1.4%, respectively. The positive predictive value (30.9%) and the negative predictive value (57.9%) for both lesions were likewise low. On the other hand, hysteroscopy was not effective in diagnosing the 27 cases of hyperplasia (26 simple and one complex) all without atypia. CONCLUSION Random endometrial sampling alone is not effective for diagnosing focal lesions of the uterine cavity and should be combined with other modalities, preferably diagnostic hysteroscopy.

Torsion of normal adnexa in postmenarchal women and risk of recurrence.

OBJECTIVE: To compare the incidence of recurrent torsion of normal adnexa to recurrent torsion of abnormal adnexa in postmenarchal women. METHODS: All cases of surgically confirmed adnexal torsion operated on in our department from January 2002 to April 2006 were retrospectively analyzed. Classification as torsion of pathologic adnexa versus torsion of normal adnexa was based on pre- and postoperative pelvic sonograms, operative findings, and pathologic diagnoses (when available). The torsion recurrence rates were evaluated by a telephone questionnaire, with 90.5% compliance. RESULTS: Twelve women had twisted normal adnexa and 50 women had twisted abnormal adnexa. The women with twisted normal adnexa were younger (25.5±7.9 years versus 31.4±11.4 years, P=.10) and had a lower median parity (0 versus 1, P=.06). Both groups had similar clinical presentations and a similar mean time from admission to surgery. The torsion recurrence rates were 63.6% (95% confidence interval [CI] 0.3–0.9) in the twisted normal adnexa group and 8.7% (95% CI 0.02–0.2) in the twisted abnormal adnexa group (P<.001). The retorsion risk of the pathologic adnexa was especially low after cystectomy (5.3%, 95% CI 0.001–0.3) or salpingo-oophorectomy (0%). The Kaplan-Meier life table analysis also showed a higher retorsion risk for normal adnexa (P=.008). CONCLUSION: The current adnexa-sparing laparoscopic management of adnexal torsion by simply untwisting may predispose to recurrent torsion of normal adnexa. The role of ovariopexy procedures in the prevention of recurrent torsion events remains uncertain. LEVEL OF EVIDENCE: III

Abortion at 18-22 weeks by laminaria dilation and evacuation.

Objective To evaluate the complications of late secondtrimester abortions (18–22 weeks) by laminaria dilation and evacuation, and the obstetric outcome of subsequent pregnancies. Methods Dilation of the cervix was achieved by repeated laminaria tent replacement. Evacuation was carried out in the outpatient clinic using general anesthesia. After the first menstrual period, all patients were invited for examination and thereafter were asked to report the outcome of subsequent pregnancies. Results One hundred seventy-one late second-trimester abortions were performed. Cervical dilation was satisfactory in 158 women (92%). Operative sonography was required in nine (5%) women. One had uterine atony. Follow-up from 150 (88%) women indicated no infection, but one woman required repeat curettage for retained products of conception. There was no indication of cervical injury on cervical internal os measurements remote from abortion. Of the 50 patients who conceived and elected to continue the subsequent pregnancies, two had premature deliveries unrelated to cervical incompetence, and all others reached term. Conclusion Late second-trimester termination by laminaria dilation and evacuation is safe and probably not associated with future adverse pregnancy outcome.

Oophoropexy to Prevent Adnexal Torsion: How, When, and for Whom?

STUDY OBJECTIVE To assess the efficacy of oophoropexy in obviating recurrent torsion and its possible long-term effects. DESIGN Case series and review of the literature (Canadian Task Force classification III). SETTING University hospital. PATIENTS Women who underwent oophoropexy for recurrent torsion of normal adnexa between 2003 and 2008. MEASUREMENTS AND MAIN RESULTS Retrieved information included the indication for oophoropexy, surgical methods, recurrence, and follow-up. Seven women underwent oophoropexy during the study period because of recurrent torsion of normal adnexa. One additional patient had experienced 3 torsion events of cystic adnexa. Surgical methods included suturing of the ovary to the pelvic sidewall or to the round ligament and plication of the utero-ovarian ligaments. Recurrence occurred in 1 of 6 patients for whom follow-up was available. All 6 patients reported spontaneous menstruation, and 2 conceived spontaneously and gave birth. Ultrasound at long-term follow-up (9-58 months) demonstrated normal ovaries. CONCLUSION Oophoropexy seems to be efficacious in preventing recurrent torsion. It is our impression that plication of the utero-ovarian ligaments has advantages over other approaches insofar as surgical feasibility and anatomical conservation.

Immunohistochemical comparison of primary peritoneal and primary ovarian serous papillary carcinoma.

Twenty-six patients, meeting strict criteria for primary peritoneal serous papillary carcinoma (PPSPC), were matched to 22 patients with ovarian serous papillary cancer (OSPC) for age and stage. Immunohistochemistry was used to determine the status of estrogen receptors (ER), progesterone receptors (PR), the expression of cell proliferation marker Ki-67, and the overexpression of HER-2/neu and p53 protein. Of the PPSPCs, 53.8% were poorly differentiated, as were 18.2% of the OSPCs (p=0.012). Positive immunostaining for ER and PR was less in PPSPCs (30.8% and 46.2%, respectively) than OSPCs (72.7% and 90.9%; p=0.003 and p=0.001, respectively). Conversely, a significant increase in the expression of Ki-67 was found in PPSPCs (37.7%) versus OSPCs (26.8%) (p=0.039). The same trend was found for HER-2/neu, being overexpressed in 38.5% of the PPSPC versus 9.1% of the OSPCs (p=0.019). Overexpression of p53 was found in 30.8% of the PPSPCs and 45.4% of the OSPCs (not significant). There was a significantly worse survival rate for PPSPCs than for OSPCs (p=0.017), yet none of the studied parameters were significantly correlated with survival within the PPSPC and OSPC groups. The significantly different immunohistochemical expression of ER, PR, Ki-67, and HER-2 in PPSPCs compared with OSPCs suggests that different molecular events may lead to tumorigenesis in these two cancers.

Polymorphisms of the p53 gene in women with ovarian or endometrial carcinoma.

The p53 gene is frequently mutated in various human tumors. Polymorphism is an additional genetic alteration observed in exons and introns of the p53 gene of normal tissues and tumors. Distributions of alleles of three common polymorphisms of the p53 gene; a 16 bp duplication in intron 3, codon 72 of exon 4 and a sequence in intron 6, were studied in peripheral white blood cells (WBC) of patients with ovarian or endometrial carcinomas. The analysis was performed by PCR and direct sequencing. The 100% linkage observed between the most common haplotypes of each polymorphism in healthy subjects was lower in the patients. A significant difference was observed between frequencies of genotype and haplotype combinations in patients with ovarian carcinoma and endometrial carcinoma. The incidence of heterozygosity was increased in ovarian carcinoma and decreased in endometrial carcinoma. Our results suggest that the p53 gene may be involved in susceptibility and predisposition to various cancers not only by mutations but also by preferential presentation of polymorphic alleles.

Tubo-ovarian abscess in older women: is the woman's age a risk factor for failed response to conservative treatment?

Objective: To assess retrospectively if there is a trend of change in the epidemiology of tubo-ovarian abscess (TOA) and to define the epidemiologic, clinical and laboratory risk factors associated with failed response to conservative antibiotic therapy. Study Design: The charts of 60 patients, admitted with clinically and sonographically diagnosed TOA between January 1995 and December 2000, were reviewed. On admission, all patients were treated with broad-spectrum antibiotics, and were divided into two groups according to the response to medical treatment. Forty-three patients, responding to antibiotic therapy, constituted group A, whereas 17 patients who did not respond and were further treated by sonographically guided drainage or surgery, were included in group B. The groups were compared with respect to patient characteristics, clinical and sonographic presentation, laboratory findings, duration of hospital stay and recovery rate of different pathogens from the endocervix. Results: The mean age of patients responding to medical therapy (group A) was significantly lower (39.6 ± 8.3) than the age of patients who did not respond (group B) (45.3 ± 6.6) (p = 0.02). The gravidity as well as the percentage of menopausal women were significantly increased in group B (p = 0.03 and p = 0.02, respectively). There was a significantly lower incidence of previous pelvic surgery and past history of PID in group B versus group A (p = 0.02 and p = 0.03, respectively), yet the duration of IUD use was significantly prolonged in group B (p = 0.02). The size of TOA, evaluated clinically and sonographically, was significantly increased in group B compared with group A (p = 0.04 and p = 0.009, respectively). Pelvic peritonitis was observed in 40% of group B patients and in none of group A patients (p = 0.0001). The only laboratory finding differentiating between the two groups was the mean sedimentation rate, being significantly higher in group B than in group A (p = 0.0005). The time interval from admission to afebrile condition as well as the duration of hospitalization were significantly shorter in group A (6.1 ± 2.3 days) than in group B (10.7 ± 4.7 days) (p = 0.00003). The incidence of positive culture from the endocervix was significantly higher in group B than in group A (p = 0.007). One hundred percent of patients in group B versus 65.2% of patients in group A were treated with triple agent therapy (p = 0.007). Conclusion: The results of the current study strengthen our previous assumption that there is probably a new trend in the epidemiology of TOA, occurring in older women, who do not present the traditional risk factors for pelvic inflammatory disease and TOA.

Can parametrectomy be avoided in early cervical cancer? An algorithm for the identification of patients at low risk for parametrial involvement

AIMS To assess the rate of parametrial involvement in a large cohort of patients who underwent radical hysterectomy for cervical cancer and to suggest an algorithm for the triage of patients to simple hysterectomy or simple trachelectomy. METHODS Multicenter retrospective study of patients with cervical cancer stage I through IIA who underwent radical hysterectomy and pelvic lymphadenectomy. The patients were divided into 2 groups according to whether or not the parametrium was involved. The two groups were compared with regard to the clinical and histopathological variables. Logistic regression of the variables potentially assessable prior to definitive hysterectomy such as age, tumor size, lymph-vascular space invasion (LVSI) and nodal involvement was performed. RESULTS Five hundred and thirty patients had specific histological data on parametrial involvement and in 58 (10.9%) patients, parametria was involved. Parametrial involvement was significantly associated with older age, tumors larger than 2 cm, deeper invasion, LVSI, involved surgical margins, and the presence of nodal metastasis. By triaging patients with a tumor ≤ 2 cm and no LVSI, the parametrial involvement rate was 1.8% (2/112 patients). With further triage of patients with negative nodes, the rate of parametrial involvement was 0% (0/107 patients). CONCLUSION Using a pre-operative triage algorithm, patients with early small lesions, no LVSI and no nodal involvement may be spared radical surgical procedures and parametrectomy. Further prospective data are urgently needed.