Long-term results of open cordectomy for the treatment of T1a glottic laryngeal carcinoma.

OBJECTIVE: To assess the long-term results and prognostic factors in patients who have undergone open cordectomy (OC) for the treatment of T(1a) glottic laryngeal carcinoma. METHODS: One hundred four epidermoid cancer patients operated from January 1989 through December 1999 were included in the study. Clinical parameters, postoperative complications, and postoperative stay were retrospectively evaluated in all cases. RESULTS: Mean survival for the patients included in the study was 61.5+/-24.8 months after the date of operation (range: 11-121 months). Ninety-four patients did not have recurrent tumor (90.4%). Local, regional and distant recurrence were linked with a statistical negative impact on survival rates (p<0.05). Only sero-hematoma was significantly related to local recurrence (p<0.05), whereas the remainder complications did not. None of the complications was associated with neck recurrence or distant metastasis (p>0.05). CONCLUSIONS: Open cordectomy is nowadays a valid technique for the surgical treatment of T(1a) glottic laryngeal carcinoma. Its results are comparable with those of other more recent techniques.

Cisplatin-induced hearing loss does not correlate with intracellular platinum concentration.

CONCLUSION: Inductively coupled plasma mass spectrometry (ICP-MS) can be applied to organic tissues obtained from experimental animals. Hearing loss does not correlate with the platinum (Pt) concentration found in the inner ear. Drug structure and affinity to inner ear proteins could explain ototoxicity caused by cisplatin. OBJECTIVES: To analyse Pt affinity for brain and ear tissues (of similar embryologic origin) in the Wistar rat and clearance gradient after a single dose, and to correlate these findings with hearing changes. MATERIALS AND METHODS: Thirty-two Wistar rats were intraperitoneally injected with cisplatin at a dose of 5 mg/kg. Animals were sacrificed after obtaining auditory brain responses (ABRs) at 3, 7, 30 and 90 days (nine, seven, seven and nine animals, respectively). Brain and both temporal bones were extracted from each animal and analysed by ICP-MS to determine the absolute concentrations of the metal. Eight non-treated animals were employed as a control group. RESULTS: The ABR thresholds were significantly elevated in animals from all groups after cisplatin treatment. A maximum accumulation of Pt for inner ear and brain was revealed around the first week: 3.175 (57%) and 0.342 (72%), respectively. Pt significantly accumulated in greater quantities in ear than in brain (p<0.01) and was cleared at a higher rate in brain than in ear (p<0.01) following cochlea/brain ratio analysis. No statistically significant correlation was found between amounts of Pt and hearing loss in the study animals.

Accumulation, fractionation, and analysis of platinum in toxicologically affected tissues after cisplatin, oxaliplatin, and carboplatin administration.

Antitumoral Pt-containing drugs present side effects like nephrotoxicity and ototoxicity. Several systematic experiments have been carried out with Wistar rats treated with cisplatin, carboplatin, and oxaliplatin to study Pt-drugs accumulation and elimination, and Pt-biomolecule distribution in the cells and cytosols of ear, kidney, and liver. Inductively coupled plasma-mass spectrometry (ICP-MS) analysis shows a cisplatin accumulation capability between oxaliplatin (the highest) and carboplatin (the lowest). The maximum concentration of Pt in all the organs studied was achieved around the first week after cisplatin treatment. During the first 30 days, the elimination was very fast, decreasing in the subsequent 60 days in all the organs. Analysis of cytosols by liquid chromatography (LC)-ICP-MS showed an analogous behavior. In most samples, the distribution of the three drugs in the cellular and cytosolic fractions was similar for all the tissues. For kidney and ear, approximately 60% and 30%, respectively, of the metal accumulated was present in the cytosol, the cytosolic fractions smaller than 50 KDa being especially important. Cisplatin-biomolecule interaction strength under denaturing conditions was evaluated by LC-ICP-MS and showed a quite strong bond.

Blebs in inner and outer hair cells: a pathophysiological hypothesis.

INTRODUCTION: The ototoxic effects of cisplatin include loss of outer hair cells, degeneration of the stria vascularis and a decrease in the number of spiral ganglion cells. Scanning microscopy has shown balloon-like protrusions (blebs) of the plasma membrane of inner hair cells following cisplatin administration. The present study was undertaken to identify the possible role of inner and outer hair cell blebs in the pathogenesis of cisplatin-induced ototoxicity. MATERIALS AND METHODS: Twenty-five guinea pigs were injected with cisplatin and their hearing tested at different time-points, before sacrifice and examination with scanning electron microscopy. RESULTS AND ANALYSIS: Seven animals showed blebs in the inner hair cells at different stages. Hearing thresholds were lower in animals showing blebs. DISCUSSION: Cisplatin seems to be able to induce changes in inner hair cells as well as in other structures in the organ of Corti. Blebbing observed in animals following cisplatin administration could play a specific role in the regulation of intracellular pressure.

The anticancer drug cisplatin induces an intrinsic apoptotic pathway inside the inner ear.

BACKGROUND AND PURPOSE: Ototoxicity is a known adverse effect of cisplatin (CDDP). Since apoptosis is involved in the development of some pathological conditions associated with the administration of anticancer drugs, we examined, using immunohistochemical and electrophysiological techniques, the apoptotic changes in the cochlea of Sprague-Dawley (SD) rats after an injection of CDDP (5 mgkg(-1) body weight). EXPERIMENTAL APPROACH: Luciferase assays were used to determine the different caspase activities and ATP levels in protein extracts of whole cochleae. The expression of several apoptotic-related proteins was measured by means of Western blotting. These analyses were performed 2, 7 and 30 days after the CDDP injection. The auditory brain stem response was obtained before and at the different times after the injection of CDDP, before the animals were killed. KEY RESULTS: CDDP significantly increased the levels of caspase-3/7 activity and active caspase-3 protein expression and caspase-3 immunofluorescence staining, caspase-9 activity, and Bax protein expression but decreased Bcl-2 protein expression within the rat cochleae. Threshold shifts were significantly elevated 2 days after CDDP treatment. CONCLUSIONS AND IMPLICATIONS: These findings support the hypothesis that cisplatin-related apoptosis evokes an intrinsic pathway of pro-apoptotic signalling within the rat cochleae. Thus, selective inhibition of the sequence of events involved in the intrinsic apoptotic pathway could provide a strategy to minimize cisplatin-induced ototoxicity.

HSP-70 as a nonspecific early marker in cisplatin ototoxicity.

CONCLUSION: The great variety of pathological entities related to the presence of circulating HSP-70 suggests a nonspecific cellular damage. As the present study shows, positive results decrease with respect to the time elapsed after the injection of the ototoxic agent. HSP-70 appears as an early and transient marker that could permit early detection of inner ear damage. OBJECTIVES: The aim of this study was to determine the presence of HSP-70 at different time points by means of Western blot immunoassay in the sera of rats treated with cisplatin. MATERIALS AND METHODS: Thirty-six Wistar rats were intraperitoneally injected with cisplatin at a dose of 5 mg/kg and blood samples were collected at 7 and 90 days. Determination of HSP-70 was made by means of a modified Western blot immunoassay kit originally used for human HSP-70 antigen detection. A control group of 18 animals was used for comparison. RESULTS: Western blot was positive in 77.8% of the animals in the 7 days group, decreasing to a 44.4% in the 90 days group. In the control group, Western blot was positive in 5.5%.

Speciation analysis of platinum antitumoral drugs in impacted tissues.

Chemical compounds containing platinum have been employed since 1978 as drugs to beat certain type of tumours. Nevertheless, besides of their exceptional antitumoral properties, these drugs also have important deleterious side effects, such as, nephrotoxicity and ototoxicity. A study of Pt accumulation and a speciation analysis has been performed by ICP-MS in samples from kidney and inner ear in a controlled population of Wistar rats treated with, either, cisplatin, carboplatin or oxaliplatin. The results on Pt accumulation point out to drug structure and not only to Pt content as the responsible for the alteration of organ functionality. Speciation studies in the samples from kidney and inner ear were performed coupling two-dimensional liquid chromatography (2D-LC) to ICP-MS. Size exclusion (SEC) and anion exchange fast protein liquid chromatography (FPLC) was employed for 2D orthogonal separation. After these separations, free drug peaks were not observed in any of the samples. The binding of Pt to biomolecules was demonstrated by SEC and, independently of the drug used, Pt eluted as two main bands with molecular weights of 12kDa and 25-65kDa for inner ear samples, and as two different bands with 20kDa and 50-60kDa in the samples from kidney. However, the relative band intensity presented important differences for the three drugs. Using the same chromatographic conditions, it was shown that a metallothionein (MT) standard eluted in the same position as some of the cytosolic Pt-biomolecules. High Pt-containing fractions eluting from the SEC column were analysed by anion exchange FPLC after a preconcentration step. Among the different preconcentration methods tested, sample focusing on the head of the FPLC column shows main advantages. In this way, the separation by 2D chromatography of the high molecular Pt-species has been considerably improved.

Endonasal endoscopic management of a large meningocephalocele in a patient with concomitant middle skull base defect.

The presence of a skull base defect can lead to major complications such as cerebrospinal fluid leak, meningocele, encephalocele and meningitis. It is exceptional to find the existence of two concomitant defects in the skull base. We present the case of a patient with concomitant spontaneous defects of the anterior and middle skull base that were surgically repaired. After 18 years of right rhinorrhea the patient was referred after being diagnosed with a large right nasal fossa meningoencephalocele, which was surgically removed by functional endoscopic sinus surgery. Following the surgery the patient complained about unilateral ear fullness. A paracentesis revealed a highly suspicious cerebrospinal fluid collection. High resolution scans revealed a defect in the mastoid tegmen; subsequently a transmastoid approach was carried out. Greater defects or those lying around the internal auditory canal, are best treated via the middle fossa approach. In the anterior cranial fossa the treatment of choice is provided by endoscopic procedures, but frontal bone craniotomy should be considered if the defect is in the frontal sinus or greater than 5 cm in size.

[External auditory canal cholesteatoma as a complication of ear surgery]. / Colesteatoma de conducto auditivo externo secundario a cirugía previa.

External auditory canal cholesteatomas are a rare disease. Their usual clinical appearance is a mass eroding the bony external auditory canal, normally in the inferior or anterior parts, with an intact tympanic membrane and a normal middle ear. A case of this uncommon disease with a review of the scientific literature is presented. Guidelines for the prevention, diagnosis and management are examined.

Central role of supporting cells in cochlear homeostasis and pathology.

HYPOTHESIS: Supporting cells have a crucial role in degenerative and regenerative events of primary sensorial hair cells of the organ of Corti. This new role should determine future studies about pathophysiology of hearing loss and its regenerative treatment. SUPPORTING EVIDENCE: Recent findings suggest an active role of supporting cells in the maintenance of hair cell function and structure. Evidences of high energy consumption and close proximity to auditory nervous fibers suggesting K+ active exchange, preferential expression of specific proteins and antigens, presence of glucocorticoids receptors, affinity for cisplatin and regenerative potential give the supporting cells an important role in homeostasis of the organ of Corti and in some specific diseases affecting this structure. CONCLUSION: As well as glial cells provide protection and regeneration to neural tissues, supporting cells may provide the necessary metabolic and electrolitic conditions for hair cells mechanical and bioelectrical function. This opens new possibilities for the treatment of apparently "irreversible" destruction of the inner ear.

Point mutation of an EYA1-gene splice site in a patient with oto-facio-cervical syndrome.

Mutations of the EYA1 gene (8q13.3) are the most common known cause of the branchio-oto-renal dysplasia (BOR), an autosomal dominant disease that includes developmental defects of branchial arch structures, middle and/or inner ear and kidney. The distinction between BOR and other dysplasias, such as oto-facio-cervical syndrome (OFC), is challenged by frequent association of the former to other diverse malformations, and by variable expressivity even within the same family. OFC is characterized by trophic alterations of the facies and shoulder girdle in addition to the malformations seen in BOR. Recent characterization of one OFC patient shed some light on the controversy over whether OFC and BOR are the same disease, and led to the hypothesis that OFC is caused by contiguous deletions of EYA1 and adjacent genes. By contrast, we show here that an OFC patient bears a single-nucleotide substitution in a splice site of EYA1. Our results indicate that not only major rearrangements, but also point mutations altering the EYA1 reading frame, can be found in patients with OFC syndrome.

Neurological complications following functional neck dissection.

A retrospective study was done to assess the incidence and factors associated with neurological complications in patients who have undergone a functional neck dissection (FND). Four hundred forty-two epidermoid cancer patients operated on from January 1984 to December 2002 were included in the study. Clinical parameters, neurological sequelae, and other complications were evaluated in all cases. The incidence of neural damage was calculated on the nerves at risk (n =714). Paralysis of the 11th nerve occurred in 12 cases (1.68%). A lesion of the marginal branch of the 7th cranial nerve was observed in nine cases (1.26%). Bernard-Horner's syndrome and hypoglossal nerve paralysis were noted in four and three cases (0.56 and 0.42%), respectively. Thus, the incidence of neurological sequelae after FND is low. Neurological complications were not associated with either clinical parameters or non-neurological complications (P >0.05). None of the factors studied can predict the appearance of neural problems in the postoperative period.

Post-transplant lymphoproliferative disease in tonsils of children with liver transplantation.

OBJECTIVE: To assess the incidence and characteristics of post-transplant lymphoproliferative disease (PTLD) in tonsils of the liver transplanted children. METHODS: All patients under 14 years of age recipients of a liver transplant at the institution and operated on for tonsillectomy under suspicion of malignancy were included in this study. RESULTS: Seven patients underwent surgery on their tonsils under suspicion of PTLD. One case of B-cell lymphoma, and three cases of polymorphic diffuse B-cell hyperplasia were found. This represents an incidence of 1.4% of PTLD in the tonsils of the 283 pediatric liver transplants performed at the hospital. CONCLUSION: The incidence of PTLD in tonsils after liver transplantation is very low at the institution. However, it is very important to follow-up allograft recipients for early diagnosis of this entity.