Predictive markers for the response to 5-fluorouracil therapy in cancer cells: Constant-field gel electrophoresis as a tool for prediction of response to 5-fluorouracil-based chemotherapy.

The prediction of response or severe toxicity and therapy individualisation are extremely important in cancer chemotherapy. There are few tools to predict chemoresponse or toxicity in cancer patients. We investigated the correlation between the induction and repair of DNA double-strand breaks (DSBs) using constant-field gel electrophoresis (CFGE) and evaluating cell cycle progression and the sensitivity of four cancer cell lines to 5-fluorouracil (5FU). Using a sulphorhodamine-B assay, colon carcinoma cells (HCT116) were found to be the most sensitive to 5FU, followed by liver carcinoma cells (HepG2) and breast carcinoma cells (MCF-7). Cervical carcinoma cells (HeLa) were the most resistant. As measured by CFGE, DSB induction, but not residual DSBs, exhibited a significant correlation with the sensitivity of the cell lines to 5FU. Flow cytometric cell cycle analysis revealed that 14% of HCT116 or HepG2 cells and 2% of MCF-7 cells shifted to sub-G1 phase after a 96-h incubation with 5FU. Another 5FU-induced cell cycle change in HCT116, HepG2 and MCF-7 cells was the mild arrest of cells in G1 and/or G2/M phases of the cell cycle. In addition, 5FU treatment resulted in the accumulation of HeLa cells in the S and G2/M phases. Determination of Fas ligand (Fas-L) and caspase 9 as representative markers for the extrinsic and intrinsic pathways of apoptosis, respectively, revealed that 5FU-induced apoptosis in HCT116 and HepG2 results from the expression of Fas-L (extrinsic pathway). Therefore, the induction of DNA DSBs by 5FU, detected using CFGE, and the induction of apoptosis are candidate predictive markers that may distinguish cancer cells which are likely to benefit from 5FU treatment and the measurement of DSBs using CFGE may aid the prediction of clinical outcome.

Expression of RAD51, BRCA1 and P53 does not correlate with cellular radiosensitivity of normal human fibroblasts.

AIMS: To evaluate the potential role of key DNA repair proteins in the sensitivity of normal human fibroblasts to ionising radiations. METHODS: Radiosensitivity of six human fibroblast strains established from skin biopsies of women who had undergone conservative breast surgery and received a curative breast conserving radiotherapy was measured by colony-formation assay. The expression level of RAD51, BRCA1 and p53 proteins were studied using western blot analysis. RESULTS: The six fibroblast strains represent a typical spectrum of normal human radiosensitivity with the surviving fraction measured for a dose of 3.5 Gy (SF3.5) ranging from 0.21 to 0.40. We found that these differences in cell survival did not correlate with the expression of RAD51, BRCA1 nor p53 in the tested normal human fibroblast strains. CONCLUSIONS: We conclude that measurement of protein expression of the three tested genes (RAD51, BRCA1 and p53) did not reflect sensitivity of normal fibroblasts to IR.

No correlation between radiosensitivity or double-strand break repair capacity of normal fibroblasts and acute normal tissue reaction after radiotherapy of breast cancer patients.

The aim was to study the relationship between cellular radiosensitivity or double-strand break (dsb) repair capacity of skin fibroblasts and the extent of acute reaction after radiotherapy for breast cancer. The study was performed with 25 breast cancer patients submitted to the radiotherapy unit of the Egyptian National Cancer Institute after conserving surgery. Dermal fibroblasts, established from skin biopsies, were used to determine the cellular radiosensitivity via colony assay and the capacity of dsb repair by constant-field gel electrophoresis. Acute reactions were scored using the Radiation Therapy Oncology Group (RTOG) classification. The spectrum of acute reactions varied from grade 1 to 4, whereby most patients developed a grade 1 reaction after total doses ranging between 46 and 70 Gy. Skin fibroblasts showed a pronounced variation in both cellular radiosensitivity expressed as the mean inactivation dose (Dbar) (coefficient of variation, CV=25%) as well as in the number of residual dsb (CV=33%) with no significant correlation between these two endpoints (r2=0.20, p=0.14). Both parameters did not correlate with the extent of acute reaction of the respective patient. The data obtained indicate that the sensitivity of fibroblasts measured either by colony assay or by dsb repair capacity is not a major parameter determining the extent of acute reaction after radiotherapy of breast cancer patients.

Electronystagmography: how helpful is it?

Two hundred and sixty patients tested with electronystagmography (ENG) for evaluation of complaints of disequilibrium were the representative sample for this study. As all new dizzy patients currently receive an ENG, the goal of this project was to determine how much an ENG adds to the diagnostic acumen, and which patients really needed an ENG in order to maximize efficiency and minimize patient cost. Results indicate the suspected diagnosis prior to ENG is assisted by its use only when the cause is thought to be central or is uncertain. The percentage of unknown causes of disequilibrium decreased from 34.2 to 13.8 per cent and the percentage of central causes increased from 13.1 to 23.1 per cent. Electronystagmography does not significantly aid in the diagnosis of peripheral lesions except as confirmation. Specific findings and recommendations are discussed.

Age and sex incidence of hypopharyngeal tumours in upper Egypt: Assuit University experience.

Three hundred and seventeen patients with hypopharyngeal tumours presented at Assuit University Hospital and were studied retrospectively with regard to sex and age incidence. Postcricoid tumours form the majority (50.1 per cent) followed by pyriform fossa tumours (26.5 per cent) and finally posterior pharyngeal wall tumours (23.4 per cent). Men form the majority (211 out of 317, i.e. 69.7 per cent). The age incidence shows two peaks at 31-35 years and 56-60 years. The first peak is formed mainly of women while the second peak is formed mainly of men.

Can pretreatment computed tomography findings predict local control in T3 squamous cell carcinoma of the glottic larynx treated with radiotherapy alone?

PURPOSE: To determine if pretreatment computed tomography findings can predict local control in T3 squamous cell carcinoma of the glottic larynx treated with radiotherapy alone. METHODS AND MATERIALS: Twenty-nine patients with previously untreated T3 squamous cell carcinoma of the glottic larynx were treated for cure with radiotherapy alone; all had a minimum 2-year follow-up. High-quality pretreatment computed tomography scans were retrospectively reviewed by a single head and neck radiologist for tumor involvement of various anatomic subsites within the larynx, and total tumor volumes were calculated for 18 of the most recent patients using a computer digitizer. A tumor score was calculated and assigned to each primary lesion depending on the extent of laryngeal spread. RESULTS: A significant decrease in the local control rate was observed for cancers involving the face of the arytenoid (11 of 20 [55%] vs. 9 of 9 [100%]; p = .02), or the paraglottic space at the false vocal cord level (7 of 16 [44%] vs. 13 of 13 [100%]; p not equal to < .01). Tumors assigned a high tumor score (6, 7, or 8) had a significantly decreased rate of local control with radiation therapy when compared with tumors assigned a low tumor score (< or = 5): 1 of 7 (14%) vs. 19 of 22 (86%) (p = .01). Total tumor volume also significantly correlated with the rate of tumor control. For tumors measuring 3.5 cm3 or less, local control was achieved in 11 of 12 patients (92%), whereas for tumors greater than 3.5 cm3, local control was achieved in 2 of 6 patients (33%) (p = .02). CONCLUSION: Pretreatment computed tomography scans can contribute significantly to the treatment decision for patients with T3 glottic carcinoma and can define a subset of patients with an excellent chance of being cured with preservation of a functional larynx after treatment with radiotherapy alone.

Relative roles of computed tomography and endoscopy for determining the inferior extent of pyriform sinus carcinoma: correlative histopathologic study.

Ten laryngopharyngectomy specimens were dissected to determine the relative accuracy of computed tomography (CT) and endoscopy under anesthesia for evaluating the inferior extent of pyriform sinus carcinoma. Endoscopic examination failed to detect involvement of the pyriform sinus apex in one patient, and considerably underestimated disease at this level in two others; CT accurately predicted the status of the apex in these three and all other patients. Endoscopy underestimated the inferior extent of tumor in six patients; CT revealed the inferior limit relative to the esophageal verge more accurately in all six of these submucosal extensions. Endoscopy revealed one case of mucosal spread to the esophageal verge not demonstrated by CT. Endoscopy and CT were both correct in revealing the esophageal verge to be involved (one case) and free of disease (two cases). This study also confirmed a common tendency of pyriform fossa cancer to spread through thyrohyoid membrane adjacent to the course of superior laryngeal neurovascular bundle (six cases). High-resolution CT, in experienced hands, is a useful adjunct to endoscopy for detecting submucosal, inferior extension of pyriform sinus carcinoma. This information can influence the choice of the lower margin of resection and method of pharyngeal reconstruction.

Complications of treatment of recurrent laryngeal papillomatosis with the carbon dioxide laser in children.

A retrospective study of the complications of treatment with the carbon dioxide (CO2) laser of 17 patients diagnosed to be suffering from recurrent laryngeal papillomatosis is presented. No immediate complications occurred except one case of laryngospasm and failure to intubate during anaesthesia leading to hypoxic encephalopathy. Three patients were completely free from disease and complications. Another patient was free from laryngeal lesions but developed a papilloma in the right tonsillar pillar. Five other patients showed one or more multiple sites of involvement in addition to the larynx. Laryngeal scarring developed in ten patients. Six patients (35.29 per cent) developed scarring as anterior glottic webs while in two scarring (11.7 per cent) occurred as posterior glottic webs. One developed scarring in the supraglottic region. The remaining one had scarring in both the glottic and supraglottic regions. One patient developed tracheal scarring necessitating laryngo-tracheal separation. Two patients were psychologically disturbed during treatment requiring psychiatric consultation and therapy.

Computed tomography of primary subglottic cancer: clinical importance of typical spread pattern.

The spread pattern of 14 cases of primary subglottic cancer, as seen on computed tomography (CT), is analyzed. Cricoid cartilage invasion was present in nine cases. Tracheal invasion was definite in four cases and questionable in three. Extralaryngeal soft tissue spread was present in nine cases; all but one had cartilage destruction. The patterns of spread seen accurately reflect reports in previous whole-organ section studies, and suggest that the elastic cone has a primary role in directing the spread of tumor. Anticipating spread to areas described above with CT and/or magnetic resonance imaging (MRI) can be used to try to improve treatment planning and perhaps outcome by: (1) avoiding placement of urgent tracheostomies close to the tumor; (2) helping to modify standard surgical approaches by suggesting lower-than-usual tracheostomies, or more extensive-than-usual thyroid gland resection; and (3) avoiding delay in diagnosis by strongly suggesting rebiopsy when imaging indicates a tumor is present, and initial endoscopy and biopsy cannot confirm the imaging findings.

Does conventional tomography still have a place in glottic cancer evaluation?

Computed tomography (CT) can detect laryngeal cancer invading the pre-epiglottic, paraglottic spaces, laryngeal cartilages, and soft tissues, but in T1 and limited T2 tumours its main value is in evaluating subglottic extent. Conventional tomography in the coronal plane has been used with reasonable success to detect both subglottic and ventricular invasion and is less expensive than CT. Twenty-nine cases of glottic carcinoma of all stages were examined clinically, endoscopically and radiographically by both coronal conventional tomography and CT. The results of these imaging studies are compared in this investigation, stressing their relationship to clinical findings (and stage), especially vocal and cord mobility. Coronal conventional tomography was found to be as accurate as CT for sublottic spread in nine cases of T1 and T2A cancer with normal vocal cord mobility. Conventional tomography had a slight tendency to overestimate ventricular and false cord involvement (two out of seven patients) with T1 glottic cancer. When mobility was impaired (four cases) or absent (15 cases), CT added data which changed staging and/or treatment plan in six cases. In seven others it was suggestive of a more advanced stage.

CT of submucosal and occult laryngeal masses.

Computed tomographic examinations were performed on 24 patients with entirely submucosal laryngeal mass lesions. Presenting complaints were hoarseness (17 patients), dysphagia (1 patient), airway obstruction (5 patients), and a cervical nodal metastasis (1 patient). The masses were visible endoscopically as submucosal bulges in 21 patients. Three other patients presenting with hoarseness and vocal cord paresis or paralysis had otherwise negative endoscopy and a mass demonstrated on CT. Thirteen patients were eventually diagnosed as having squamous cell carcinoma, which was the primary working diagnosis following CT in 12 cases. The group of 13 carcinoma patients had a range of two to five endoscopic procedures with one to four negative biopsies and a 6 week to 9 month delay in histologic confirmation of cancer. Other lesions included five laryngoceles, two chondrosarcomas, and one case each of paraganglioma, fibrosarcoma, lymphoma, and tuberculous laryngitis. Computed tomography is an indispensable tool for evaluating submucosal laryngeal masses or otherwise unexplainable symptoms (usually hoarseness) that might herald such a mass. A definite submucosal mass on CT should prompt a deep or wedge biopsy to reach a pathologic diagnosis. This will avoid the delay in diagnosis that frequently occurs in these patients.