Induction chemotherapy with cisplatin and 5-fluorouracil followed by chemoradiotherapy or radiotherapy alone in the treatment of locoregionally advanced resectable cancers of the larynx and hypopharynx: results of single-center study of 45 patients

BACKGROUND: Induction chemotherapy with cisplatin and fluorouracil and radiotherapy is an effective alternative to surgery in patients with carcinoma of the larynx and hypopharynx who are treated for organ preservation. METHODS: We designed a protocol to evaluate the possibility of organ preservation in patients with advanced, resectable carcinoma of the larynx and hypopharynx. Forty-five eligible patients who were followed up between April 1999 and May 2001 were enrolled. Initially, these patients were treated with two cycles of induction chemotherapy consisting of cisplatin, 20 mg/m2/day on days 1 to 5, and 5-fluorouracil, 600 mg/m2/day by continuous infusion on days 1 to 5. Patients who had a complete response to chemotherapy were treated with definitive radiotherapy; patients who had a partial response to chemotherapy were treated with chemoradiotherapy. Cisplatin, 35 mg/m2/week, was introduced throughout the duration of radiotherapy. Patients who had no response or progressive disease underwent surgery with postoperative radiotherapy. Patients with N2 or N3 positive lymph nodes underwent neck dissection after the treatment. RESULTS: The mean age was 56.6 years (range, 34-75 years). The overall response rate to induction chemotherapy was 71.1%, with a 17.8% complete response rate and 53.3% partial response rate. With a median follow-up of 13.7 months, 23 (51.1%) of all patients and 63.3% of surviving patients have had a preservation of the larynx or hypopharynx and remain disease free. The most common toxicities were nausea and vomiting and mucositis. CONCLUSION: Organ preservation, with multimodality treatment, may be achievable in some of the patients with resectable, advanced larynx or hypopharynx cancers without apparent compromise of survival.     

Incidence of childhood brain tumors in Syria (1993-2002)

OBJECTIVE: To determine whether the incidence and location of childhood CNS tumors in Syria follows the same pattern described in Western and Far Eastern countries. PATIENTS AND METHODS: We analyzed the data compiled from 367 children with brain tumors operated on in our Department of Neurosurgery between 1993 and mid-2002. We excluded all vascular and metastatic lesions and adopted the latest WHO classification in grouping all glial tumors. RESULTS: We found that 47% of brain tumors were located in the supratentorial, and 53% in the infratentorial region. The ratio of male to female occurrence was 1:1.2 (52% males, 48% females). For lesions in the supratentorial space, the distribution was 56% males and 44% females, while in the posterior fossa, the distribution was 61% males and 39% females. Low-grade tumors (WHO I/II) constituted 53.5% of all lesions, and the rest were high grade tumors (WHO III/IV) 46.5%.The most common tumor found in our childhood population was medulloblastoma (27.5%), followed by astrocytoma (25.8%), then craniopharyngioma (14.1%). The most common tumor in the posterior fossa was medulloblastoma (53.5%), followed by astrocytoma (22.5%), then ependymoma (17%). The most common tumors in the supratentorial space were astrocytoma and craniopharyngioma. CONCLUSIONS: In our patient population, the incidence and distribution of CNS tumors were somehow different than those reported by authors from the Western and Far Eastern countries. Whether these results are unique to Syria, or reflect a regional difference in the disease distribution between the Middle East region and the rest of the world, remains to be determined.     

The anatomical basis for surgical preservation of temporal muscle

OBJECT: Mobilizing the temporal muscle is a common neurosurgical maneuver. Unfortunately, the cosmetic and functional complications that arise from postoperative muscular atrophy can be severe. Proper function of the muscle depends on proper innervation, vascularization, muscle tension, and the integrity of muscle fibers. In this study the authors describe the anatomy of the temporal muscle and report technical nuances that can be used to prevent its postoperative atrophy. METHODS: This study was designed to determine the susceptibility of the temporal muscle to injury during common surgical dissection. The authors studied the anatomy of the muscle and its vascularization and innervation in seven cadavers. A zygomatic osteotomy was performed followed by downward mobilization of the temporal muscle by using subperiosteal dissection, which preserved the muscle and allowed a study of its arterial and neural components. The temporal muscle is composed of a main portion and three muscle bundles. The muscle is innervated by the deep temporal nerves, which branch from the anterior division of the mandibular nerve. Blood is supplied through a rich anastomotic connection between the deep temporal arteries (anterior and posterior) on the medial side and the middle temporal artery (a branch of the superficial temporal artery [STA]) on the lateral side. CONCLUSIONS: Based on these anatomical findings, the authors recommend the following steps to preserve the temporal muscle: 1) preserve the STA; 2) prevent injury to the facial branches by using subfascial dissection; 3) use a zygomatic osteotomy to avoid compressing the muscle, arteries, and nerves, and for greater exposure when retracting the muscle; 4) dissect the muscle in subperiosteal retrograde fashion to preserve the deep vessels and nerves; 5) deinsert the muscle to the superior temporal line without cutting the fascia; and 6) reattach the muscle directly to the bone.     

Kainate down-regulates a subset of GABA<Subscript>A</Subscript> receptor subunits expressed in cultured mouse cerebellar granule cells

The effect of kainate, an agonist selective for ionotropic AMPA/kainate type of glutamate receptors, on GABAA receptor subunit expression in cultured mouse cerebellar granule cells was studied using quantitative RT-PCR, ligand binding and electrophysiology. Chronic kainate treatment, without producing excitotoxicity, resulted in preferential, dose- and time-dependent down-regulation of alpha1, alpha6 and beta2 subunit mRNA expression, the expression of beta3, gamma2 and delta subunit mRNAs being less affected. The down-regulation was reversed by DNQX, an AMPA/kainate-selective glutamate receptor antagonist. A 14-day kainate treatment resulted in 46% decrease of total [3H]Ro 15-4513 binding to the benzodiazepine sites. Diazepam-insensitive [3H]Ro 15-4513 binding was decreased by 89% in accordance with very low amount of alpha6 subunit mRNA present. Diazepam-sensitive [3H]Ro 154513 binding was decreased only by 40%, contrasting >90% decrease in alpha1 subunit mRNA expression. However, this was consistent with lower potentiation of GABA-evoked currents in kainate-treated than control cells by the alpha1-selective benzodiazepine site ligand zolpidem, suggesting compensatory expression of alpha5 (and/or alpha2 or alpha3) subunits producing diazepam-sensitive but zolpidem-insensitive receptor subtypes. In conclusion, chronic kainate treatment of cerebellar granule cells selectively down-regulates oil, alpha6 and beta2 subunits resulting in altered GABAA receptor pharmacology.     

Salmonella typhi endocarditis: a case report

Salmonella are a rare cause of infective endocarditis. This report describes a case where Salmonella typhi was isolated from the blood and urine of a patient with echocardiographically documented aortic valve disease and endocarditis. The patient was treated with two weeks of ceftriaxone (3 g/day) and amikacin (15 mg/kg/day), followed by a further two weeks of ceftriaxone (3 g/day) alone. He made a complete recovery.     

Reproductive disturbances,pituitary lactotrope adenomas,and mammary gland tumors in transgenic female mice producing high levels of human chorionic gonadotropin

To assess the consequences of prolonged exposure to elevated levels of LH/human chorionic gonadotropin (hCG) in the female, we developed a transgenic (TG) mouse model (hCGbeta+) that overexpresses the hCGbeta-subunit cDNA. Because of the promoter used, ubiquitin C, the transgene is expressed in multiple tissues, including the pituitary gland, in which coupling with the endogenous common alpha-subunit results in synthesis of high levels of bioactive hCG. The TG females presented with precocious puberty, infertility, enhanced ovarian steroidogenesis, and abnormal uterine structure. Pituitary enlargement was evident from the age of 2 months, which progressed to adenomas by the age of 10-12 months. Immunohistochemical studies and electron microscopy demonstrated lactotrope origin for the adenomas, associated with severe hyperprolactinemia. The mammary glands of TG females showed marked lobuloalveolar development followed by mammary tumors with characteristics of adenocarcinoma at the age of 9-12 months. More than 90% of penetrance and high frequency of metastasis (47%) was observed. Formation of the pituitary and mammary gland tumors was totally abolished by ovariectomy despite persistently elevated hCG levels. Taken together, these findings suggest that the hCG-induced aberrations of ovarian function are clearly responsible for the extragonadal tumors observed in these TG mice.     

Biweekly irinotecan plus bolus 5-fluorouracil and folinic acid in patients with advanced stage colorectal cancer

OBJECTIVE: In this study, we evaluated the efficacy and tolerability of biweekly irinotecan (CPT-11) plus 5-fluorouracil (5-FU) and folinic acid (FA) regimen (IFL) in patients with advanced stage colorectal cancer. METHODS: A total of 28 patients were examined. The median age was 51 years (range, 30-74 years). One treatment cycle consisted of CPT-11 180 mg/m(2) on days 1 and 15; 5-FU 425 mg/m(2) on days 1, 2, 15 and 16; and FA 20 mg/m(2) on days 1, 2, 15 and 16, every 4 weeks. A total of 119 cycles (median, 4.0 cycles) were administered. Of the 28 patients, 18 received the chemotherapy as first line treatment, seven received it as second line and three received it as third line. RESULTS: An overall objective response rate of 21.5% was achieved in the patient group. However, the overall response rate for the 18 patients receiving first line treatment was 27.7%. The median response duration was 10.5 months (range, 3-19 months). An additional 28.6% of the patients had stable disease for a median duration of 6.5 months (range, 3-8 months). Median time to disease progression was 4.5 months (range, 1-22+ months) and median overall survival time was 11+ months (95% confidence interval, 9-15 months). Toxicities were mild and manageable. CONCLUSIONS: We conclude that biweekly IFL is a practical and tolerable treatment option with a disease control rate of 50.1% in patients with advanced stage colorectal cancer.     

Hypereosinophilia and metastatic anaplastic carcinoma of unknown primary

The differential diagnosis of eosinophilia may sometimes be difficult. Eosinophilia may occur in a diverse array of conditions from parasitic infestations to malignacies. Idiopathic hypereosinophilic syndrome has also been described. A 65-year-old male patient presenting with eosinophilia of obscure etiology is described in the present report. Three years after the diagnosis of eosinophilia, metastatic anaplastic carcinoma of unknown primary was detected. Differential diagnosis is disscussed briefly. It is stressed that patients with hypereosinophilia of unknown etiology must be screened for malignancy regularly during follow up.