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OBJECTIVE: To evaluate the benefits of a diagnostic hysteroscopy prior to in vitro fertilization. PATIENTS AND METHODS: We retrospectively studied 145 patients who underwent ICSI during a period of 6 months. Office hysteroscopy was systematically performed before the first stimulation cycle. If pathological findings were revealed, appropriate medical or surgical treatment was given. RESULTS: Pathological patterns were observed in 45% of hysteroscopies. Endometritis, polyps and myomas and mucosal diseases were the most frequently observed. The patients aged over 38 years didn't show higher rate of pathology (29% vs 27% for the younger patients). The treatment of pathologies gave the same pregnancy rate than the normal cavities. Patients with endometritis were treated with antibiotics and 40% of them became pregnant in the following cycle. DISCUSSION AND CONCLUSION: Systematic hysteroscopy prior to IVF-ICSI showed to be an effective investigation that could improve the pregnancy rate.

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OBJECTIVES: The aim of this study is to determine the efficacy of L-N-acetyl-cysteine (L-NAC) as a protectant for inner ear auditory sensory cells against the toxic effects of cisplatin. STUDY DESIGN: Prospective laboratory study of the otoprotective effect of L-NAC on auditory neurons and hair cells in vitro. METHODS: The study has two arms. The first arm evaluated the neuroprotective effect of L-NAC on early postpartum auditory ganglion cell cultures. Two culture media were used. The two media differed in that one of them was enhanced by the addition of neurotrophins (neurotrophin type 3 and brain-derived neurotrophic factor) and a growth factor (transforming growth factor-beta1). Then the survival of cisplatin-treated auditory neurons was studied before and after pretreatment with protective levels of L-NAC. The second arm of the study evaluated the effect of L-NAC on cisplatin damage initiated to auditory hair cells. Early-postpartum organ of Corti explants were grown in culture. Their rate of survival was studied after exposure to toxic levels of cisplatin. Then, survival of cisplatin-damaged hair cells was studied after they were pretreated with L-NAC. RESULTS: Pretreatment of cultures with L-NAC protected both auditory neurons and hair cells from the effects of exposure to toxic levels of cisplatin. This observed otoprotective effect was dose dependent. CONCLUSIONS: Our in vitro studies have demonstrated that L-NAC protected both auditory neurons and hair cells from the toxic effects of cisplatin. Because it protects both of these inner ear structures, L-NAC may be potentially useful in protecting hearing, in general, from cisplatin-induced damage. In addition, L-NAC has low systemic and mucosal toxicity. It also has a low molecular weight that may allow it to readily cross the round window membrane. All these characteristics make it potentially suitable for transtympanic application for the prevention of the ototoxicity of cisplatin in vivo.

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Cisplatin (cis-diamminedichloroplatinum(II) (CDDP)) is a widely used, highly effective, oncolytic agent that has serious ototoxic side-effects. To test the effectiveness of local delivery, of L-methionine (L-Met) as an otoprotective agent against CDDP ototoxicity, we used a rat model of a highly metastatic breast cancer tumor, i.e. Fisher 344 rats implanted with MTLn3 breast cancer cells. Four experimental groups were evaluated--I: untreated; II: CDDP-treated (three dosages); III: systemically-delivered L-Met + CDDP-treated; IV: locally delivered L-Met + CDDP-treated. The integrity of the outer hair cells (OHCs) was determined using scanning electron microscopy (SEM); hearing was assessed by recording auditory brainstem responses (ABRs) at multiple frequencies. The chemotherapeutic effectiveness of CDDP was quantified by measuring changes in tumor mass and the presence of tumor metastasis. L-Met provided otoprotection of the OHCs against CDDP toxicity in the cochleae of rats following either systemic (III) or local (IV) administration. The ABRs were unchanged in each of the L-Met protection Groups (III and IV) and in the untreated animals of Group I. Treatment with CDDP only (II) induced significant hearing losses at both 16 and 18 kHz when compared to ABRs of untreated rats(I). CDDP was effective in controlling the MTLn3 initiated breast cancer tumors in the CDDP-treated (II) and the local L-Met protection, CDDP-treated (IV) Groups. In contrast, the tumors in the systemic L-Met protection, CDDP-treated Group (III) were not controlled by the CDDP treatment regime. This study demonstrates that local delivery of L-Met to the scala tympani of the cochlea via the round window membrane (IV) provides effective protection against CDDP ototoxicity without compromising its ability to control a highly metastatic form of cancer.

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OBJECTIVE: To evaluate the efficacy of esterified hyaluronic acid (MeroGel) as a middle ear (ME)-packing material. DESIGN: Randomized controlled trial. MATERIAL: Twenty-four guinea pigs. INTERVENTION: Group 1, MeroGel-treated animals (n = 10), bilateral wounding of ME mucosa with 5 of the animals receiving the MeroGel packing in the left ME and 5 of the animals receiving MeroGel in the right ME; group 2, absorbable gelatin sponge-treated animals (n = 10), with the same experimental protocol as in group 1 except that the absorbable gelatin sponge was the packing material; group 3, untreated animals (n = 4), unilateral wounding of the left ME mucosa in 2 animals and in 2 animals in the right ME, with no packing material. Auditory brainstem recordings were performed for all groups before the ME operation and 5 days and 6 weeks after the operation. RESULTS: Auditory brainstem response recordings at postoperative day 5 showed that all ears with ME packing had hearing losses in the frequency range of 500 to 4000 Hz. The recovery of hearing acuity at postoperative week 6 was significantly better in group 1 (MeroGel-treated) guinea pigs compared with group 2 (the absorbable gelatin sponge-treated) animals. In group 2 animals, 20% of the packing material remained in the ME cavities and new bone formation was observed, while in group 1 animals, there was less packing material in the ME and no formation of new bone. CONCLUSIONS: MeroGel is a nonototoxic packing material with a high level of biocompatibility for ME mucosa; it is an effective supportive material following ME surgery and is easily expelled from the ME cavity.

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PURPOSE: This article discusses the use of the 2-piece Le Fort I osteotomy to gain access to the cranial base and the authors' experiences with this technique. METHODS: Medical records of patients who required surgical access to the cranial base were retrospectively reviewed, and demographic data, procedures done, postoperative results, and complications were recorded. RESULTS: Nine patients underwent a 2-piece Le Fort I osteotomy. Complications included development of a pseudoaneurysm of the internal carotid artery in 1 patient, 2 cerebrospinal fluid leaks, both of which resolved, and 1 patient who lost 2 teeth and some associated bone. CONCLUSION: The 2-piece Le Fort I osteotomy provides excellent access to the clival region of the cranial base with minimal complications.

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OBJECTIVE AND IMPORTANCE: Aneurysmal bone cysts (ABC) are benign bone neoplasms which typically involve the spine and long bones. We present a rare case of an ABC in the temporal bone with significant cerebellar compression. CLINICAL PRESENTATION: The patient was a young boy who presented with several weeks of left posterior auricular pain. Computed tomography, magnetic resonance imaging and angiogram showed an expansile bone neoplasm involving the left petrous temporal bone. INTERVENTION: A retrosigmoid-transmastoid craniectomy was performed, and total removal of the bone lesion was achieved. The pathological examination revealed the diagnosis of ABC. CONCLUSION: The postoperative course was uneventful, and the imaging studies demonstrated total removal of the neoplasm. This case represents the imaging and surgical management of a rare ABC in the temporal bone. This diagnosis should be considered in the differential of bone neoplasms in this region.

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OBJECTIVE: This study describes the technique and efficacy of split calvarial graft cranioplasty for the reconstruction of retrosigmoid/suboccipital defects following surgery for acoustic neuromas. STUDY DESIGN: A prospective study of the technique of split calvarial graft cranioplasty, its postoperative healing, and incidence of postoperative headache. METHODS: The technique requires splitting of the craniotomy bone flap into outer and inner table bone grafts. The combination of both bony grafts allows the coverage of a wider area of posterior fossa dura. This technique was used in 18 patients. All patients were followed for a minimum of 6 months. Eleven of 18 patients were followed for 1 year or longer. Four patients had three-dimensional computed tomography of their skull and area of split calvarial bone graft. RESULTS: One of 18 patients had a persistent disabling headache at 1 year postoperatively. A natural contour of the retrosigmoid area was achieved in all patients. Three-dimensional computed tomography scan, obtained 6 months postoperatively, showed total coverage of the retrosigmoid area and fusion of the bone flap to the surrounding skull. CONCLUSION: The technique of split calvarial grafting of posterior fossa defects is a feasible, safe, and effective way of separating the nuchal musculature and posterior fossa dura. The technique also allows the restoration of the contour and bony covering of the retrosigmoid area. The technique is a simple alternative to other types of cranioplasties aimed at reducing the incidence of postoperative headache in patients with acoustic neuromas.

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OBJECTIVE: To determine the feasibility and efficacy of using a bone cement, Oto-Cem, to reconstruct the ossicular chain. STUDY DESIGN: Prospective clinical trial on nine consecutively chosen adult patients with ossicular chain defects. PATIENTS AND SETTING: Nine patients with ossicular chain defects involving the long process of the incus were treated at the Carolina Ear and Hearing Clinic. The ossicular chain was reconstructed using bone cement by itself or in conjunction with a stapes prosthesis. MAIN OUTCOME MEASURES: Preoperative audiograms were compared with audiograms 3, 6, and 12 months after reconstruction. RESULTS: There was a mean pure-tone average (PTA) improvement of 15 dB in patients undergoing incus to stapes suprastructure reconstruction with the bone cement. The incus to mobile footplate reconstruction (using a stapes prosthesis attached to the newly reconstructed incus) resulted in a 34-dB PTA postoperative improvement. Two of the three patients with incus to oval window repairs experienced a 10-dB improvement in PTA. One of the three patients experienced a loss in speech discrimination and a 2-dB loss in PTA. CONCLUSIONS: Despite the limited number of patients, this preliminary study demonstrates the effectiveness of Oto-Cem in reconstructing a foreshortened incus. There was a substantial hearing improvement in all but one patient in the incus to stapes or the incus to footplate categories.

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Regeneration/repair and protection of auditory hair cells and auditory neurons is an exciting, rapidly evolving field. Simultaneous developments in the fields of otobiology and surgical otology have led to new and exciting possibilities in inner ear medicine and surgery; specifically, the treatment or prevention of a variety of types of hearing losses in the foreseeable future. Sensorineural hearing loss in humans is commonly associated with a loss of auditory hair cells. It has been generally accepted that hearing loss resulting from hair cell damage is irreversible because the human ear has been considered to be incapable of regenerating or repairing these sensory elements following severe injury. An organ of Corti explant study has shown that it is possible to initiate the regeneration/repair of mammalian hair cells. In this study, ototoxin-damaged organ of Corti explants from juvenile rats were treated with a combination of retinoic acid (10-8M) and fetal calf serum (10%). TGF-alpha has been identified as a growth factor capable of evoking auditory hair cell regeneration/repair in ototoxin-damaged organ of Corti explants. Preliminary in vitro experiments with juvenile rat organ of Corti explants and in vivo studies in the cochleae of adult guinea pigs indicate that pretreatment followed by continuous treatment of the inner ear with a combination of retinoic acid and TGF-alpha can protect the auditory hair cells from the ototoxic effects of aminoglycosides. Because the integrity of spiral ganglion neurons is also essential for normal auditory function, there is a parallel series of in vitro and in vivo studies of the effects of neurotrophic factors on the survival of auditory neurons and the regeneration of injured neuronal processes. Clinical studies have demonstrated that it is now possible to perform surgeries on the inner ear, i.e., partial or total labyrinthectomies, and maintain hearing. The field of cochlear implantation has also provided insights into both the short- and long-term effects of cochlear fenestration on inner ear function. Administration of growth factors to the inner ears of animals is now possible with the use of implanted catheters and miniature infusion pumps. These advances suggest that localized application of drugs to the human inner ear may be feasible. The aim of this paper has been to provide an overview of advances in the study of the biology of auditory hair cells and auditory neurons, as well as recent relevant surgical advances. Taken together, these advances in otobiology and surgery will, in the future, be combined to devise new and innovative treatments for inner ear disorders.

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HYPOTHESIS: Cisplatin causes the generation of reactive oxygen species (ROS), which interferes with the antioxidant defense system of Corti's organ and results in damage to the hair cells. BACKGROUND: Cisplatin is a widely used chemotherapeutic agent with the dose-limiting side effect of ototoxicity. Evidence is accumulating that cisplatin interferes with the antioxidant defense system of Corti's organ. METHODS: Organotypic explants of P-3 rat organ of Corti were the in vitro model system. Presence of intact auditory hair cells and stereocilia bundle integrity was assayed by phalloidin-FITC staining. Fluorescent dye probes detected H2O2 and intracellular thiol [e.g., glutathione (GSH)]. Spectrophotometric analysis determined antioxidant enzyme levels. RESULTS: There was a rapid dose-dependent cisplatin cytotoxicity in the explants after 48 h of exposure. An accumulation of H2O2 and a reduction of GSH levels were observed within cisplatin-exposed hair cells. L-buthionine sulfoximine, an inhibitor of GSH formation, enhanced cisplatin ototoxicity, whereas N6-(2-phenylisopropyl) adenosine, an adenosine agonist, elevated antioxidant enzyme levels and ameliorated cisplatin toxicity. The following molecules protected hair cells from cisplatin-induced damage: GSH; glutathione diethyl ester (GSHe); ebselen (EBS); 4-methylthiobenzoic acid (MTBA); and D-methionine (D-MET). EBS, MTBA, and D-MET in vitro protection correlates with in vivo protection in rats. CONCLUSIONS: Organotypic culture of Corti's organ has been validated as a model for studying cisplatin toxicity and for screening otoprotective molecules. Some of the events that contribute to cisplatin's ability to damage auditory hair cells are generation of ROS (e.g., H2O2), depletion of intracellular GSH, and interference with antioxidant enzymes within the cochlea. Agents that bolster the cochlea's antioxidant system can prevent cisplatin destruction of auditory hair cells. Identified protective agents may prove to be clinically useful in limiting or completely protecting from cisplatin ototoxicity.

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PURPOSE: To determine the computed tomographic (CT), magnetic resonance (MR) imaging, and angiographic findings of papillary endolymphatic sac tumors. MATERIALS AND METHODS: Clinical and imaging studies in 20 patients (aged 17-65 years) with histopathologically proved papillary endolymphatic sac tumors were retrospectively reviewed. Patients underwent CT (n = 18), MR imaging (n = 15), or angiography (n = 12). CT scans were evaluated for bone erosion and calcification; MR images, for signal intensity, enhancement patterns, and flow voids; and angiograms, for tumoral blood supply. RESULTS: All tumors were destructive and contained calcifications centered in the retrolabyrinthine region at CT. The MR imaging appearance varied with lesion size; 12 of 15 tumors showed increased signal intensity at T1-weighted imaging. The high-signal-intensity area was circumferential in lesions 3 cm or smaller and was scattered throughout the lesion in advanced tumors. Only tumors larger than 2 cm had flow voids. The blood supply arose predominantly from the external carotid artery. Large tumors had additional supply from the internal carotid and posterior circulation. CONCLUSION: Papillary endolymphatic sac tumors are destructive, hypervascular lesions that arise from the temporal bone retrolabyrinthine region. Increased signal intensity at unenhanced T1-weighted MR imaging is common and may help distinguish these lesions from more common, aggressive temporal bone tumors.

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Aggressive papillary tumors of the temporal bone are neoplasms that are locally invasive and destructive. Previously classified on histologic study as middle ear adenomas or adenocarcinomas, observational evidence suggested that they arose from endolymphatic sac. To evaluate this hypothesis, we established a tissue culture from cells derived from such a papillary tumor and compared immunohistochemical stains of the original tumor with stains on endolymphatic epithelium. Similarities in expression of neuroectodermal antigens were observed. Similar staining antigens in cells derived from tumor and the endolymphatic sac provide evidence that epithelium from endolymphatic sac is the site of origin for these aggressive neoplasms. In tissue culture the cells remain contact inhibited and dependent on serum or growth factors with survival beyond the expected senescence at 30 to 50 generations. Therefore the cell culture technique provides a model for study of the disruption of growth control and invasive properties of this tumor.

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Aggressive papillary tumors of the temporal bone are neoplasms that were recently re-classified as tumors of the endolymphatic sac. They typically invade the mastoid bone and otic capsule and can grow into the petrous apex. The authors have treated three patients with this rare neoplasm and grown one of the tumors in tissue culture. This report reviews the clinical presentation in the three patients and the immunohistochemical staining characteristics of the tumor and tumor culture as compared to those of the endolymphatic sac. Findings support the hypothesis that aggressive papillary lesions of the temporal bone arise from the endolymphatic sac. Additionally, it is noted that the tumor culture maintains the characteristics of the original tumor and thus provides an exciting laboratory model for further study of this rare neoplasm.

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With the continued concern over the possible transmission of viral infections through homologous middle ear implants, there is increasing pressure to develop a truly biocompatible alloplastic middle ear prosthesis. The polymaleinate ionomer, which has been used in dentistry as a filling and luting material for more than 15 years, has recently been used to construct total and partial ossicular replacement prostheses. In an attempt to evaluate these new implants, a multicenter prospective clinical trial was initiated. To date, 92 patients have undergone implantation. The follow-up interval ranged from 3 months to 22 months. Although it is premature to discuss the long-term results, the preliminary surgical experience and audiometric data with these implants are reviewed. From a surgical perspective, the ionomeric prostheses were easily contoured with a diamond burr and were not prone to shattering. Preliminary follow-up audiometric data were available on 80 patients (59 partial ossicular replacement prostheses and 21 total ossicular replacement prostheses). Of the 59 partial ossicular replacement prostheses the air-bone gaps (average of 500 Hz, 1 kHz, 2 kHz and 3 kHz) were as follows: 0 dB to 10 dB, 15 (25%) of 59; 11 dB to 20 dB, 20 (34%) of 59; 21 dB to 30 dB, 11 (19%) of 59; and greater than 30 dB, 13 (22%) of 59. Of the 21 total ossicular replacement prostheses the air-bone gaps were as follows: 0 dB to 10 dB, 6 (29%) of 21; 11 dB to 20 dB, 6 (29%) of 21; 21 dB to 30 dB, 5 (24%) of 21; and greater than 30 dB, 4 (19%) of 21.

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The endolymphatic sac is part of the membranous labyrinth; it plays an important role in the hearing mechanism. Injury to the endolymphatic sac may, over time, severely compromise hearing. The endolymphatic sac is located in a duplication of the dura of the posterior aspect of the petrous pyramid and is, therefore, in the surgical field of many neurosurgical operations performed on the posterolateral cranial base. The endolymphatic sac was exposed bilaterally in 10 anatomic specimens; the distance from the center of the sac to the posterior lip of the internal auditory meatus and to the XIth nerve in the jugular foramen was measured with a caliper. Also measured was the distance between the center of the sac and the closest point on the petrous ridge and the distance between that point and the petro-sigmoid intersection. The petro-sigmoid intersection was defined as the point at which the medial aspect of the sigmoid sinus intersects the lateral aspect of the petrous ridge. The dimensions of the sac were also recorded. On the average, the sac was found to be 15.7 mm posterosuperior (superolateral) to the XIth nerve in the jugular foramen (range, 11.0-18.5 mm) and 13.3 mm posterior (lateral) to the internal auditory meatus (range, 10.0-18.0 mm). The center of the sac was 24.1 mm (mean value) (range, 20.0-28.0 mm) in front of the petro-sigmoid intersection at a point 11.5 mm (mean value) (range, 8-17 mm) below the petrous ridge. The mean width and height of the sac were 3.83 (range, 2-6 mm) and 3.80 mm (range, 2.5-8 mm), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

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Vestibular schwannomas typically present with erosion of the temporal bone that is limited to the boundaries of the internal auditory canal. Four patients with extensive erosion, excavations, and pseudosatellite defects in the petrous apex are presented. These bony changes extended anteriorly up to the level of the carotid canal. The patients did not have stigmata of neurofibromatosis type 2 and they did not have systemic bony disorders. The tumors did not show any unusual histopathologic changes. Such invasive tumors present an unusual surgical challenge compared to vestibular schwannomas with a more typical pattern of bony erosion. Radiological features and surgical considerations relevant to vestibular schwannomas with this rare presentation are discussed.

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Human erythropoietin in concert with intraoperative hemodilution, tumor embolization, and surgical staging was used to manage a red blood cell mass in an anemic Jehovah's Witness patient with a hypervascular meningioma. Erythropoietin (3000 U thrice weekly) and oral iron (1300 mg daily) were given for 1 month prior to surgery, raising the hemoglobin level from 11.8 to 14.1 gm/100 ml. A posterior fossa craniectomy combined with a temporal craniectomy was then performed so that partial petrosectomy, section of the transverse sinus, incision of the tentorium, and exposure of the lesion could be carried out. The first stage of the surgery was terminated immediately prior to tumor mobilization. Isovolemic hemodilution was initiated just before the skin incision. Postoperatively, the hemoglobin concentration dropped to 11.5 gm/100 ml. The erythropoietin dose was doubled and administration of oral iron continued, leading to a hemoglobin level of 14.0 gm/100 ml at 1 month after the first operation. The tumor was embolized using superselective catheterization. The next day, at the second stage of the surgery, the tumor was extirpated, again employing isovolemic hemodilution. By the 4th postoperative day, the hemoglobin level had dropped to 9.4 gm/100 ml. The patient made an uncomplicated recovery. Erythropoietin therapy contributed substantially to the successful outcome of this case. Since erythropoietin has the potential to augment all other forms of autologous banking, its role in elective neurosurgery may become increasingly important in an era of heightened concern about heterologous transfusion.

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The origin of the cholesterol granuloma is controversial; however, it is believed to result from an inflammatory response of the temporal bone to an obstruction of the pneumatized air cells. Hemorrhage into the air cells results in a foreign-body reaction and progressive granuloma formation. As the process develops, bone is eroded by this expansile lesion, often involving the middle ear, the petrous apex, and the cerebellopontine angle. We present the first reported case of cholesterol granulomas manifesting as bilateral intradural lesions adjacent to the temporal lobes. The fact that it presents bilaterally with sclerotic mastoids makes this presentation even more unique. Its location might cast controversy on the existing theories of development. A literature review of the cholesterol granuloma will be discussed, relating it to this patient's unusual presentation.

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We originally described the transcranial translabyrinthine approach (TCTL) to acoustic neuroma. The approach is a labyrinthine dissection that is performed via the suboccipital exposure. It allows a complete and direct visualization of the internal auditory canal and the identification of the facial nerve at "Bill's bar." The TCTL enhances the suboccipital approach and adapts to its concepts of the classical transmastoid translabyrinthine approach. We hereby report our initial experience with the TCTL and present the surgical results in six additional cases. We also discuss the indications of this approach and compare it to alternative approaches that are used for the removal of large acoustic neuromas that extend laterally in the internal auditory canal.

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The field of Skull base Surgery evolved rapidly over the past several years. The techniques that were developed now make it possible to treat lesions that were previously deemed inaccessible. This article is a review of some of the aspects of this evolving specialty. Three representative cases will be presented and discussed with special emphasis on patient selection, surgical complications and postoperative rehabilitation.

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