Epithelial Inclusion Research Articles

Laparoscopic management of peritoneal endometriosis, endometriotic cysts, and rectovaginal adenomyosis.

Peritoneal endometriosis is probably caused by the implantation of regurgitated menstrual cells. The ovarian endometrioma is the consequence of non-hormone-regulated bleeding from intraovarian epithelial inclusions after they have undergone metaplasia into endometrial-like tissue. Rectovaginal adenomyosis is, in fact, an adenomyotic lesion and can develop from Müllerian rests. In conclusion, peritoneal endometriosis, ovarian endometriosis, and rectovaginal adenomyotic nodules must be considered as three separate entities with different pathogeneses that require a different therapeutic approach.

Bilateral extraocular muscle epithelial inclusion cysts as a complication of strabismus surgery

This is a case report of bilateral extraocular muscle epithelial inclusion cysts found in the body of the muscle, not just involving the tendon or the new tendon–scleral interface, after strabismus surgery in a 3-year-old boy with consecutive exotropia. Histologic review of the cysts confirmed the presence of inclusion cysts originating from proliferating conjunctival epithelium occurring in the body of both medial rectus muscles. We postulated that the occurrence of bilateral inclusion cysts might have caused the persistent postoperative localized inflammatory response. Epithelial inclusion cysts are often noted in periocular locations such as the conjunctiva, caruncle, eyelids, and cornea. Rarely are they noted in the body of an extraocular muscle. 1 Histologically, epithelial inclusion cysts are nests of proliferating epithelial cells with a laminated keratinized center of sloughed cells. Etiology is attributed to viable epithelial cells being displaced into the subdermal, subconjunctival, or episcleral space as a complication of surgery, inflammation, or both. 1,2 We present what to our knowledge is the first reported case of bilateral extraocular muscle inclusion cysts after strabismus surgery. CASE REPORT A 3-year-old boy had consecutive exotropia that developed after bimedial rectus recession at 7 months of age to treat infantile esotropia. Postoperative inflammation was treated with 3 weeks’ administration of prednisolone acetate (Pred Forte; Allergan, Irvine, CA) 4 times per/d. Ten months after surgery, intermittent consecutive exotropia manifested when the patient was fatigued. A small inflammatory nodule existed in the right eye, and the patient was restarted on Pred Forte drops 3 times/d for 3 weeks. When we saw the patient, 28 months after bimedial rectus recession, our impression was exotropia (20 prism diopters) with right hypertropia (10 to 15 prism diopters), worse on right gaze (Fig 1). His visual acuity was 20/30 OD, 20/30 in the left eye OS, and 20/20 OU. A mass was noted in the right nasal area per both gross and slit lamp examination. This mass was in the area of his previous medial rectus insertion and appeared to present a mechanical obstruction to complete adduction of the right eye. Versions were otherwise normal in the right eye as well a the left eye. We performed the patient’s surgery when he was 3 years old, at which time we encountered a sub-Tenon’s cyst in the right eye. The cyst measured 5.0 mm in height, and it covered the tendon and muscle body of the recessed medial rectus (Figure 1, top). The cyst was dissected free

Lack of proliferative activity of surface epithelial inclusion cysts of the ovary.

Surface epithelial inclusion cysts (SEICs) of the ovary are epithelial inclusions in the ovarian cortex believed to form from invagination of the surface epithelium at the time of ovulation. It has long been theorized that SEICs are related to the development of epithelial ovarian cancer. Ki-67 antigen is a marker of cell proliferation and has been shown to be prognostic in epithelial ovarian cancer. The purpose of this study was to evaluate Ki-67 activity in SEICs to evaluate their possible connection to ovarian neoplastic proliferation. A retrospective review of benign ovaries removed at the time of pelvic surgery was performed. Slides were immunostained with Ki-67. Proliferation index, expressed as the percent of cells staining in SEICs, was calculated. Proliferative activity was scored as negligible, low, moderate, or high, at <5%, 5-10%, 11-40%, and >40%, respectively. Eighteen ovaries from 18 women were evaluated. The percentage of Ki-67 positive cells ranged from 0% to 7%. Ki-67 activity in SEICs of the ovary is negligible to low. Proliferative activity as assessed by Ki-67 staining does not explain any possible relationship of SEICs to epithelial ovarian cancer.

Ectopic Breast Tissue as a Possible Cause of False-Positive Axillary Sentinel Lymph Node Biopsies

Epithelial inclusions representing ectopic breast tissue are uncommonly seen in axillary lymph nodes. The extensive histopathologic examination of axillary sentinel lymph nodes of patients with breast carcinoma may increase the chances to encounter tiny foci of ectopic breast tissue, which may be misinterpreted as (micro)metastatic disease and lead to unwarranted completion of axillary dissection and to inaccurate staging and improper adjuvant treatments for the patients. Here we report on seven cases of ectopic breast tissue in axillary sentinel lymph nodes. In three cases there were coexistent micrometastases, and in the remaining cases the ectopic tissue was not associated with metastatic disease. The ectopic breast tissue showed remarkably varied morphologic features, including apocrine metaplasia and proliferative changes indistinguishable from those occurring in sclerosing adenosis and florid epithelial hyperplasia of the breast. A peripheral layer of myoepithelial cells was consistently detected in the ectopic glands and ducts. Besides awareness and purely morphologic criteria, a false-positive identification of these inclusions as metastatic carcinoma may be avoided by the use of immunohistochemical reactions for the localization of specific markers of the myoepithelial cell component, which is associated with the ectopic breast tissue.

Inferior conjunctival autograft for primary pterygia

Objective Superior conjunctival graft is commonly used in pterygium surgery, which may adversely affect the outcome of future filtration surgery. We retrospectively studied the success rate of inferior conjunctival autografting for primary pterygia in our unit. Design A noncomparative, retrospective, interventional case series. Participants Thirty eyes of 27 patients treated between August 1996 and February 2001 with primary pterygia. Intervention Excision of pterygium followed by conjunctival autograft harvested from the inferior bulbar conjunctiva. Surgeries were performed by an experienced surgeon (CL) in 23 patients and by trainees in the remaining four cases. Main outcome measures Recurrence of the pterygium and complications. Results Mean follow-up was 27 months (range, 8–53). Recurrence occurred in one eye (3.3%). This was a white female in her early fifties, with recurrence detected 3 months after the surgery. Conjunctival scarring at the donor site was observed in 11 eyes (36.66%). There was no symblepharon formation. There was no restriction of up gaze. Hemorrhage under the conjunctival graft developed in three eyes, corneal dellen near the limbus developed in four eyes, and epithelial inclusion cysts at the recipient site developed in two eyes. Conclusions Inferior conjunctival autografting is an effective technique with a low recurrence rate. This is a useful technique in cases in which it is not possible or desirable to use the superior conjunctiva as a donor source.

Benign heterotopic epithelial inclusions in axillary lymph nodes. Histological and immunohistochemical patterns.

Benign heterotopic epithelial inclusions in axillary lymph nodes are an extremely rare condition that must be differentiated from metastatic carcinoma. We describe 2 histologically different examples of benign epithelial inclusions in nonsentinel axillary lymph nodes, each with an unusual clinical presentation.

Benign Heterotopic Epithelial Inclusions in Axillary Lymph Nodes

Abstract Benign heterotopic epithelial inclusions in axillary lymph nodes are an extremely rare condition that must be differentiated from metastatic carcinoma. We describe 2 histologically different examples of benign epithelial inclusions in nonsentinel axillary lymph nodes, each with an unusual clinical presentation.

Type III female genital mutilation: Clinical implications and treatment by carbon dioxide laser surgery

Objective: The purpose of this study was to examine clinical implications of type III female genital mutilation and to evaluate the use of carbon dioxide laser surgery to restore vulvar opening and to treat associated epithelial inclusion cysts. Study design: Twenty-five infibulated patients underwent carbon dioxide laser treatment. Seven of the women (28%) were pregnant, between 10 and 37 weeks of gestation. Vulvar examination revealed five cases of epidermal inclusion cysts. One pregnant patient, with a cyst that was 7 cm in diameter, was at 24 weeks of gestation. Deinfibulation was performed in an outpatient setting with local anesthesia. A colposcopy-guided laser beam was used to create an incision along the fusion midline of the labia majora. In case of vulvar epidermal inclusion cyst, the capsule was opened and emptied of sebaceous contents; the inner surface of the cyst was vaporized completely. Results: The carbon dioxide laser procedure restored a complete vulvar opening in all 25 patients. The complete vaporization of cyst capsule was possible in all five cases. No case of intraoperative or postoperative complication occurred. The average duration of follow-up was 11 months. Four patients who underwent deinfibulation antenatally had labor with spontaneous vaginal delivery and no evidence of perineal trauma. Conclusion: On the basis of the advantages that were observed, deinfibulation treatment must be offered to all infibulated patients. The procedure is particularly appropriate during pregnancy to prevent childbirth complications. Laser carbon dioxide has been proved to be a suitable technique for the treatment of female genital mutilation when inclusion cysts are associated with it. (Am J Obstet Gynecol 2002;187:1550-4.)

Epibulbar Osseous Choristoma: Case Report and Review of the Literature

Epibulbar osseous choristoma is a choristomatous lesion of the conjunctiva containing bone. Originally called epibulbar osteoma, this lesion was first described by von Graefe in 1863. We discuss a case of a 4-year-old patient who presented with an epibulbar lesion consistent histopathologically with an epibulbar osseous choristoma, and report a review of the literature. The differential diagnosis of osseous choristoma should include classical limbal dermoids, epithelial inclusion cysts, prolapsed orbital fat, papillomas, dermolipomas, and complex choristomas. Although the rarest of epibulbar choristomas, 51 epibulbar osteomas have now been reported in the medical literature. Most commonly, this variety of choristoma presents as an isolated epibulbar lesion within the supratemporal quadrant but may occur in other locations on the surface of the globe and possibly in conjunction with other choristomatous tissue as much as 10% of the time. Frequently, they may involve the muscle or have dense attachments to the underlying sclera. Osseous choristomas most likely represent congenital lesions with a potential for slow growth but may occur in association with trauma. Options for management include observation or surgical excision. When surgery is contemplated, preoperative radiographic imaging may be helpful for assessing adhesion to the sclera or extraocular muscles.

Corneal epithelial inclusion cyst in a dog

An unilateral corneal epithelial inclusion cyst in a 7-year-old male Boxer dog is reported. The cyst had been observed for thirty days, was unique, not congenital and only one eye was involved. Seven months prior to the referral the dog had manifested indolent corneal ulcer treated with grade keratotomy and third eyelid flap. The cyst was removed by superficial keratectomy followed by a conjunctival pedicle graft. Recovery was uncomplicated and there wasn’t recurrence seven months after the surgery.

VEGF expression and enhanced production by gonadotropins in ovarian epithelial tumors.

Vascular endothelial growth factor (VEGF) is a heparin-binding, dimeric polypeptide with potent mitogenic effects on endothelial cells. VEGF expression has also been reported in ovarian epithelial tumors (OETs), which may be associated with gonadotropin stimulatioin. We recently reported that most OETs, including OET cell lines, express gonadotropin receptors. Here we studied VEGF mRNA expression in 141 OET and 35 benign ovarian samples using reverse transcriptase polymerase chain reaction and in situ hybridization (ISH). We also studied VEGF production by OET cell lines under stimulation of gonadotropins. AO (serous carcinoma), low malignant potential (LMP; SV40-transformed borderline tumor) and ML-5 (SV40-transformed cystadenoma) cells were examined for VEGF protein production under the regulation of gonadotropins in vitro. The biologic function of VEGF was confirmed by using bovine endothelial growth assay. Whereas VEGF was not detected in benign ovarian surface epithelium or in ovarian epithelial inclusions, it was detected in both epithelial and stromal compartments of OETs. For VEGF epithelial expression, only 5% of ovarian cystadenomas and 30% of borderline tumors were positive for VEGF detection by ISH, whereas VEGF mRNA signal was detected in 80% of ovarian carcinoma cases. This increment of VEGF expression in ovarian carcinomas was statistically significant compared with benign and borderline tumors. Within ovarian carcinomas, the percentage of VEGF-positive cells was significantly associated with the grade of cancer but not with cancer cell types or cancer stages. Both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) stimulated the expression of VEFG(165) in AO cells in a dose-dependent manner. Maximal induction was obtained for FSH at dose of 40 mIU/ml and for LH at 50 mIU/ml after 48 hr of culture. Compared with the nonstimulated cells, VEGF level was significantly elevated in both LMP and AO cells after stimulation of gonadotropins. Furthermore, the induction of VEGF expression was significantly stronger in carcinoma cells than in borderline OET cells. These observations suggest that VEGF may play a role in the development of ovarian cancer and that the elevated gonadotropins, as found in menopause and in most ovarian cancer patients after surgery, could accelerate tumor growth and tumor recurrence by inducing VEGF expression in OETs.

The Pathology of Experimental Aerosolized Monkeypox Virus Infection in Cynomolgus Monkeys (Macaca fascicularis)

Cynomolgus monkeys (Macaca fascicularis) were exposed by fine-particle aerosol to lethal doses of monkeypox virus, Zaire strain. Death, attributable to fibrinonecrotic bronchopneumonia, occurred 9 to 17 days postexposure. Lower airway epithelium served as the principal target for primary infection. The relative degree of involvement among lymphoid tissues suggested that tonsil, mediastinal, and mandibular lymph nodes were also infected early in the course of the disease, and may have served as additional, although subordinate, sites of primary replication. The distribution of lesions was consistent with lymphatogenous spread to the mediastinal lymph nodes and systemic dissemination of the virus through a monocytic cell-associated viremia. This resulted in lesions affecting other lymph nodes, the thymus, spleen, skin, oral mucosa, gastrointestinal tract, and reproductive system. The mononuclear phagocyte/dendritic cell system was the principal target within lymphoid tissues and may also have provided the means of entry into other systemic sites. Hepatic involvement was uncommon. Lesions at all affected sites were characterized morphologically as necrotizing. Terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining of select lesions suggested that cell death within lymphoid and epithelial tissues was due in large part to apoptosis. Skin and mucosal surfaces of the respiratory and gastrointestinal tracts also exhibited variable proliferation of epithelial cells and subjacent fibroblasts. Epithelial intracytoplasmic inclusion bodies, consistent with Guarnieri bodies, were usually inconspicuous by light microscopy, but when present, were most readily apparent in the stratified squamous epithelium of the oral mucosa and epidermis. Multinucleated syncytial cells were also occasionally observed in the stratified squamous epithelium of the tongue, tonsil, and skin, and in the intestinal mucosa. Monkeypox virus antigen was readily demonstrated by immunohistochemistry using anti-vaccinia mouse polyclonal antibodies as well as anti-monkeypox rabbit polyclonal antibodies. Detectable poxviral antigen was limited to sites exhibiting obvious morphologic involvement and was most prominent within epithelial cells, macrophages, dendritic cells, and fibroblasts of affected tissues. The presence of poxviral antigen, as determined by immunohistochemistry, correlated with ultrastructural identification of replicating virus. Concurrent bacterial septicemia, present in one monkey, was associated with increased dissemination of the virus to the liver, spleen, and bone marrow and resulted in a more rapidly fatal clinical course.

Expression of calretinin in human ovary, testis, and ovarian sex cord-stromal tumors.

Calretinin, a calcium-binding protein, is primarily expressed in certain subtypes of neurons. It has also been found to be present in mesothelial cells and mesotheliomas but not in many types of carcinomas. Using a polyclonal anti-calretinin antibody, we investigated the expression of calretinin immunohistochemically in nonneoplastic human ovaries and testes and ovarian sex cord-stromal tumors (SCSTs). In ovaries, calretinin was expressed in theca interna cells, hilus cells, and scattered individual stromal cells. Oocytes, granulosa cells, theca externa cells, rete ovarii, and most stromal cells were negative. Expression of calretinin was also seen in the ovarian surface epithelium and in collapsed and flat epithelial inclusion glands (EIGs), but not in round, columnar, and ciliated EIGs. In some glands, a transition from calretinin-positive to calretinin-negative epithelium was observed. In postpubertal testes, calretinin was expressed in Leydig cells, but not in germ cells or most rete testes and Sertoli cells. In ovarian SCSTs, strong calretinin staining was seen in all hilus cell tumors (4/4) and the Leydig cell component of Sertoli-Leydig cell tumors (10/10). The Sertoli cell component showed focal weak positivity in 5/10. Fibrothecomas were completely negative (0/8). In granulosa cell tumors, the tumor cells were either completely negative (8/14) or weakly positive at the periphery of the tumor (6/14) while scattered stromal cell staining was seen in 9/14 cases. The expression of calretinin in normal Leydig cells, theca interna cells, the Leydig cell component of Sertoli-Leydig cell tumors, and hilus cell tumors suggests its functional relationship with androgen production. Its pattern of expression in ovarian SCSTs is useful in the differential diagnosis of these tumors. The presence of a transition from calretinin-positive, flat, nonciliated epithelium to calretinin-negative, columnar, ciliated epithelium in the same glands provides strong evidence for mullerian metaplasia.

Needle aspiration and endodiathermy treatment of epithelial inclusion cyst of the iris

PURPOSE: To report a case of recurrent epithelial inclusion cyst of the iris treated with needle aspiration and endodiathermy. METHODS: Case report. A 27-year-old man with a history of congenital cataracts, congenital nystagmus, cataract surgery in each eye at 3 years of age, and a long-standing iris epithelial cyst presented with decreased vision of 20/400 in the better seeing left eye. The reduced vision was diagnosed secondary to growth of the iris inclusion cyst over the pupil. RESULTS: The iris cyst, which occluded the chamber angle and pupil, was treated with aspiration, separation of the cyst wall from the cornea, and endodiathermy. Twelve months after cyst surgery, no evidence existed of epithelial cyst regrowth. The visual function was significantly improved, although Snellen visual acuity was unchanged at 20/400. CONCLUSION: The minimal invasiveness of needle aspiration and diathermy can result in a satisfactory outcome without undertaking more extensive and invasive surgical treatments for epithelial inclusion cysts of the anterior chamber.

Ultraviolet light induces reactivation in a murine model of cutaneous herpes simplex virus-1 infection.

We have developed a model of cutaneous herpes simplex virus-1 (HSV-1) reactivation in SKH-1 hairless mice which closely mimics the condition in humans. Sixty plaque-forming units of HSV-1 strain 17 syn+ were applied to a superficially abraded area on the lateral body wall. More than 85% of mice developed primary HSV-1 infection characterized by a zosteriform pattern of cutaneous vesiculation and ulceration. Approximately one-third of mice with primary skin lesions succumbed to neurologic disease and in the remaining mice cutaneous lesions healed completely. Subsequent exposure of healed areas to two minimal inflammatory doses of UV resulted in recrudescence of skin lesions in the irradiated areas in almost 60% of mice. Lesions appeared approximately 4 days after irradiation, persisted for 3-5 days and then resolved completely. Reactivation rarely resulted in death due to neurologic disease. Primary lesions had a histologic appearance typical of cutaneous HSV-1 infection with vesicles and focal epithelial necrosis accompanied by the formation of epithelial syncytial cells and the presence of herpetic intranuclear inclusion bodies. In primary lesions HSV-1 was demonstrated by immunohistochemistry, polymerase chain reaction and culture. In reactivated lesions epithelial syncytia and inclusion bodies were not seen; however, virus was demonstrable by polymerase chain reaction and culture. Exposure of the uninfected side to UV did not stimulate disease recurrence suggesting that local effects of UV rather than systemic immunosuppression were responsible for reactivation. Reactivation could also be obtained with two minimal inflammatory doses of UV from a UV-340 light source which emits light approximating the solar spectrum.

Anterior Vaginal Wall Sling for Female Stress Urinary Incontinence

Background: The purpose of this study was to determine the efficacy and safety of the anterior vaginal wall sling in the management of women with stress urinary incontinence. Materials and Methods: From January 1998 to December 1999, 42 patients(31 with genuine stress urinary incontinence and 11 with mixed urinary incontinence, 38 with anatomical incontinence and 4 with intrinsic sphincteric deficiency) underwent anterior vaginal wall sling at Yeungnam University Hospital were studied retrospectively. The mean age was 49.3 years(ranging from 34 to 66 years of age) and the mean follow-up period was 29.4 months(ranging from 16 to 40 months). Intra- and postoperative complication. success rate and patient's satisfaction were evaluated. Results: The mean operation time was 79 minutes(ranging from 65 to 124 minutes) and the mean hospital stay was 5.1 days(ranging from 4 to 10 days). Mean postoperative Foley catheter drainage was 2.1 days(ranging from 1 to 5 days). As a complication. bladder perforation occurred in one patient(2.4%). residual urine sensation developed in seven patients(16.7%), and suprapubic pain was complained in five patients(11.9%), which improved gradually. Vaginal epithelial inclusion cyst occurred in one patient(2.4%) at postoperative 31 months. Four(9.4%) patients with de novo instability were improved by anticholinergics medication. The success rate was 92.9% and 38 patients(90.5%) were satisfied with this procedure. Conclusion: We consider that the anterior vaginal wall sling to be a safe and effective surgical procedure for the treatment of female stress urinary incontinence, but a longer follow-up is necessary to determine long term effect.

Decreased Luteinizing Hormone Receptor mRNA Expression in Human Ovarian Epithelial Cancer

Objectives. The objective of this study was to examine the distribution and cellular localization of luteinizing hormone receptor (LHR) in ovarian epithelial tumors (OETs) and their presumed precursor lesions—ovarian epithelial inclusions (OEIs). The clinicopathologic correlation of the receptor expression in OET was also examined.Methods. Fifteen microdissected samples of ovarian surface epithelium (OSE), 20 OEIs from benign ovaries, and 141 OETs, including 48 cystadenomas, 33 borderline tumors, 60 carcinomas, and 5 metastatic cancers, were examined for LHR expression by using reverse transcription polymerase chain reaction and in situ hybridization. LHR expression in tumor epithelium and tumor stroma was analyzed separately. The clinicopathologic correlation data were analyzed by standard analysis of variance and contingency table methods.Results. LHR expression was identified in the majority of OSE and OEI samples. In OETs, LHR positivity was found in the epithelial cells in 27% of cases and in the stromal compartment in 37% of cases. LHR-positive stromal cells were mainly luteinized cells. Within the tumor epithelium, LHR expression was detected in 42% of benign, 24% of borderline, and 17% of malignant OETs. LHR expression in tumor stroma showed a similar trend of reduction from benign to malignant OETs. Within the 17 carcinomas, LHR was expressed in the epithelium in 47% of grade 1, 12% of grade 2, and only 5% of grade 3 cancers. The mean age of the LHR-positive group was younger than that of the receptor-negative patients. Compared with mucinous and other types of OETs, serous OETs showed higher LHR expression in the epithelium. Compared with the OETs removed in the different menstrual phases, OETs in the secretory phase showed higher LHR in the tumor stroma than in the proliferative phase. No receptor mRNA was detected in the epithelium of five carcinomas metastatic to the ovary. LHR transcription splicing variants from a single previous report were confirmed in this study.Conclusions. Malignant OETs have significant reduction of LHR expression compared with precursor lesions and benign and borderline OETs. LHR expression shows a steady decline from low-grade to high-grade ovarian cancer. The presence of LHR receptor in tumor epithelium suggests that luteinizing hormone in serum may have direct influence on tumor growth, whereas the receptor in tumor stroma may be indicative of a paracrine function of LH in the development of OETs.

Vulvar epithelial inclusion cyst as a late complication of childhood female traditional genital surgery

Epithelial inclusion cysts may be a late complication of traditional female genital surgery. We present the case of a 19-year-old Eritrean woman who had been circumcised at birth and sought treatment for an enlarging vulvar mass that arose after the onset of puberty. Symptoms included pain, pruritus, and interference with walking. (Am J Obstet Gynecol 2000;183:509-10.)

Laser in situ keratomileusis to correct residual myopia and astigmatism after radial keratotomy

Purpose To evaluate the safety and efficacy of laser in situ keratomileusis (LASIK) in selected post-radial-keratotomy (RK) eyes with residual myopia and astigmatism. Setting TLC—The Brea Laser Eye Center, Brea, California, USA. Methods Nine eyes of 6 patients who had had RK but had residual myopia and/or astigmatism had LASIK. All RK eyes had 8 radial incisions, were more than 1 year post-RK, had no epithelial inclusion cysts or corneal disease, and had had no subsequent ocular surgery. Follow-up was a minimum of 13 months, at which time uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), manifest refraction, cycloplegic refraction, keratometry, central and peripheral pachymetries, intraocular pressure, and a subjective assessment of visual function were obtained. Results At the last follow-up, the mean spherical equivalent (SE) was −0.156 diopter (D) ± 0.174 (SD). All eyes treated for distance vision had a UCVA of 20/25 or better. No patient lost BCVA. No intraoperative or postoperative complications occurred. Seven eyes had morning and evening measurements. The mean change in manifest SE from morning to evening was −0.143 D. Six of the 7 eyes (86%) had 0 to 1 Snellen line change in UCVA from morning to evening. The subjective questionnaire revealed a high degree of satisfaction with overall vision, minimal glare, and less fluctuation in daily vision than before LASIK. Conclusion Laser in situ keratomileusis is safe and efficacious for reducing residual myopia and astigmatism in properly selected RK patients.

Absence of premalignant histologic, molecular, or cell biologic alterations in prophylactic oophorectomy specimens from BRCA1 heterozygotes.

The high mortality associated with ovarian carcinoma is largely a reflection of the inability to diagnose the disease at an early stage; the identification of a histologic lesion or molecular marker associated early stages of transformation would represent an important advance in understanding the natural history of this cancer. The existence of individuals with germline mutations in the ovarian and breast carcinoma susceptibility gene BRCA1 represents a unique opportunity to search for such premalignant alterations in ovarian tissues that are at unusually high risk for tumorigenesis. In this study, the authors addressed the hypothesis that pathologically normal ovaries removed from BRCA1 heterozygotes are likely to display premalignant histologic, molecular, and/or cell biologic alterations that may provide insight into early stages of ovarian tumorigenesis. Ovarian tissues from 18 BRCA1 heterozygotes and from 20 age-matched controls were examined in a blinded fashion for histologic evidence of surface epithelial pseudostratification, epithelial inclusion cysts, deep cortical invaginations of surface epithelium, increased stromal cell activity, and surface papillomatosis. Immunohistochemical analyses for expression of BRCA1, p53, and ERBB-2 and quantitation of cell proliferation (Ki-67 expression) and apoptosis (TUNEL assay), were also performed on all specimens. Although histologic alterations were observed, there was no difference in frequency between cases and controls. Analysis of BRCA1 expression revealed ubiquitous nuclear immunoreactivity in the surface epithelial cells of all ovaries. Similarly, no evidence was found of p53 overexpression in any ovarian tissue or of a difference in ERBB-2 expression between cases and controls. Finally, no differences were observed in epithelial cell proliferation or apoptosis. Clinically, normal ovaries from BRCA1 heterozygotes do not show evidence of premalignant alterations in histology, molecular markers, cell proliferation, or apoptosis, indicating that such changes are likely rare.