Combined-modality therapy in locally advanced primary rectal cancer

PURPOSE: Patients with unresectable, locally advanced rectal cancer are reported to have a dismal prognosis. The aim of this study was to analyze the effect of combined-modality therapy on clinical outcome. METHODS: From March 1990 to December 1997, 43 patients (28 males; median age, 62 years; median follow-up, 74 months) with locally advanced (T4 and/or N3) nonmetastatic rectal cancer received external-beam radiation (23.6 plus 23.6 Gy (split course), 8 patients; 45 Gy, 35 patients) plus 5-fluorouracil (96-hour continuous infusion, Days 1–4, at 1,000 mg/m2/day) and mitomycin C (10 mg/m2, intravenous bolus, Day 1). Concomitant chemotherapy was repeated at the beginning of the second course (split-course group) or in the last week of radiotherapy (continuous-course group). After 6 to 8 weeks, patients were evaluated for surgical resection and intraoperative radiation therapy (10 to 15 Gy). Thereafter, adjuvant chemotherapy (5-fluorouracil plus leucovorin, 6–9 courses) was prescribed. RESULTS: During chemoradiation, 5 patients (11.6 percent) developed Grade 3 to 4 hematologic toxicity. After chemoradiation, 29 patients (67.4 percent) had an objective clinical response (complete response, 2.3 percent; partial response, 65.1 percent). Thirty-eight patients underwent radical surgery (anterior resection, 24 patients; abdominoperineal resection, 14 patients; intraoperative radiation therapy boost on the tumor bed, 19 patients), and 2 patients had partial tumor resection. No perioperative deaths occurred in the patient group. Five-year survival and local control rates were 59.9 and 69.1 percent, respectively. Distant metastasis occurred in 44.2 percent of patients. Statistically significant relationships between intraoperative radiation therapy and local control (P = 0.0104), radical surgery and survival (P = 0.0120), and adjuvant chemotherapy and disease-free survival (P = 0.0112) were observed. CONCLUSIONS: Our data suggest that combined-modality therapy was relatively well tolerated and resulted in good local control and survival. With regard to the impact of surgical resection on survival, additional studies aimed at improving the local response rate are necessary, whereas the positive impact of intraoperative radiotherapy on local control appears to justify the inclusion of this therapeutic modality in prospective multi-institutional trials.     

Silent sinus syndrome: a case presentation and comprehensive review of all 84 reported cases

OBJECTIVES: The term silent sinus syndrome has been used to describe the constellation of progressive enophthalmos and hypoglobus due to gradual collapse of the orbital floor with opacification of the maxillary sinus, in the presence of subclinical chronic maxillary sinusitis. Currently, it is believed to occur as a result of the sequence of events following maxillary sinus hypoventilation due to the obstruction of the ostiomeatal complex. METHODS: In this study, we present a case of true silent sinus syndrome. In addition, we highlight the previously published cases of silent sinus syndrome, as well as provide a review of the etiology, pathophysiology, radiologic diagnosis, surgical treatment, and pitfalls to avoid in the management of patients with silent sinus syndrome. RESULTS: Eighty-three previously published cases of silent sinus syndrome were reported in the literature and are summarized in this review. CONCLUSIONS: A well-defined set of criteria is needed to classify a patient under the diagnosis of silent sinus syndrome, which include enophthalmos and/or hypoglobus in the absence of clinically evident sinonasal inflammatory disease.     

Prevention and treatment of congenital toxoplasmosis: organization protocol

AIM: Prevention and treatment of congenital toxoplasmosis are still a matter of debate among obstetricians, pediatricians and epidemiologists. There is no consensus about antenatal screening and diagnostic tests, nor there is about treatment for presumed infection in pregnancy. As an example of this type of organisation for health care delivery, a regional model has been promoted as a multidisciplinary approach for prenatal diagnosis of congenital toxoplasmosis. The model had been designed on the national guidelines of the National Health Institute (Istituto Superiore di Sanità, ISS). METHODS: Suspected maternal infections are referred and seen as outpatients at our centre on a specific day of the week; maternal investigation (specific IgG, IgM, IgA and IgG avidity titres) are performed at the Institute of Virology of the University of Bari, and patients are started on spiramycin. All cases of true or presumed seroconversion are counselled for amniotic fluid sampling and the sample is sent to ISS. In cases of late seroconversion and positive amniotic fluid results, patients are prescribed pyrimethamine+sulphonamide+folinic acid and alternate spiramycin until the end of pregnancy. A fetal-neonatal follow-up is performed in all cases. RESULTS: During the period 1999-2001, 180 cases of presumed toxoplasmosis infection have been referred (average 60 cases per year). We have been able to reclute, since the adoption of the national network protocol, 1/3 of presumed regional cases with a positive increasing trend. CONCLUSION: The service for prenatal diagnosis of toxoplasma gondii infection has definitely benefitted from the adoption of this protocol, which combines adherence to a national network and pays respect to regional requirements.     

Efficacy of computed tomographic image--guided endoscopic sinus surgery in residency training programs

OBJECTIVE: To determine the efficacy of computed tomographic image-guided endoscopic surgery in the hands of inexperienced surgeons. STUDY DESIGN: Four second-year otolaryngology residents, with no prior experience performing ethmoidectomies, performed endoscopic sinus surgery (ESS) on formalin-fixed human cadaveric specimens with and without the aid of computer-assisted surgery (CAS). METHODS: Each resident was asked to identify critical sinus, orbital, and skull base structures while performing a total ethmoidectomy and multiple sinusotomies. Their surgical accuracy (percentage of correctly identified structures), total operative time, and incidence of major complications were recorded for each side. A total of 16 sides were evaluated (8 with and 8 without CAS). Statistical significance between groups was determined by means of Pearson's chi2 analysis. RESULTS: Statistical analysis showed a significant difference (P = .001) in the mean accuracy of identifying critical anatomical landmarks between the CAS (97%) and non-CAS (76.8%) groups. Although not statistically significant, operative time appeared to be longer in the group using CAS (average of 67 vs. 80 min). Three major intracranial complications were documented only in the group not using CAS. CONCLUSIONS: Although, unquestionably, a thorough knowledge of the anatomy remains essential for performing ESS, CAS improves surgical accuracy and reduces the risk of major intracranial or intraorbital complications for residents. In additional, our data suggest that this technology may enhance surgical efficiency and improve the learning curve by reducing operative time (below one's normal baseline) while maintaining a greater than 90% accuracy in identifying critical anatomical landmarks.     

CONTROL OF GENE ACTIVITIES IN THE POLYTENE CHROMOSOMES OF Chironomus tentans BY ECDYSONE AND JUVENILE HORMONE

The injection of ecdysone (molting hormone) into chironomid larvae is known to result in the stimulation of specific gene activities (increased RNA synthesis). The morphological manifestation of this gene activation is the formation of a puff. Cytological and autoradiographic analysis of several regions of the salivary gland chromosomes of Chironomus tentans revealed that ecdysone also stimulates Balbiani ring 1. In contradistinction to the puffs, the Balbiani rings are tissue specific and account for a significant percentage of the cell's non-nucleolar RNA.The application of juvenile hormone results in a decreased activity of Balbiani ring 1, suggesting that the two hormones may act antagonistically. In addition, juvenile hormone induces a puff at chromosome region I-19-A and this puff becomes less active after a short-term treatment with ecdysone. These data demonstrate an effect of juvenile hormone on puffing and are the first to demonstrate activation of a Balbiani ring by ecdysone.     

Chemoradiation in cervical carcinoma: a must?

Cervical carcinoma is one of the most frequent gynecological malignancies. Literature shows that while the rate is exceedingly low in systematically screened populations, the incidence remains high because of large populations of at-risk women--particularly in underserved nations and in medically indigent subpopulations of Western nations--who are not screened. Recently, a series of randomized trials has demonstrated the possibility to dramatically improve the prognosis of these patients by using concurrent chemoradiation. In particular, concurrent chemoradiation represents a major treatment option in patients with bulky IB-IIA disease, IIB-IVA disease and resected IB-IIA disease with poor prognostic factors. However, further studies are necessary to optimize treatment schedules and particularly to define the best drug combination to be used during radiation therapy, improve patients selection by the analysis of anatomical (TNM stage) and non-anatomical (tumor oxygenation, genetic markers, tumor angiogenesis) prognostic factors, explore novel treatment strategies, such as use of neoadjuvant chemoradiation in locally advanced tumors, integration of antiangiogenetic therapies in chemoradiation schedules, use of supportive treatments aimed to overcome tumor hypoxia, to evaluate the possibility of 'cure' of locally recurrent tumors by chemoradiation and finally to define the best 'second-line' treatment for patients failing after chemoradiation with or without surgery.     

Impact of dose and volume on radiation-induced mucositis

There is a relationship between a given radiation dose and the resulting biological effect in the management of head and neck cancer. Radiation mucositis represents a frequent complication in cancer chemoradiation. Its prevention and treatment are major goals in radiation therapy schedules. Critical tissues can be spared using high conformal radiation therapy (3DCRT) based on consensus guidelines for target volume. Current approaches to radiation mucositis with respect to the dose and volume impact are illustrated. The monitoring system of late toxicity used by the authors is presented.     

Evaluating the effectiveness of evidence-based guidelines for the use of spacer devices in children with acute asthma

OBJECTIVE: To change standard practice from using nebulisers to metered dose inhalers and holding chambers (spacers) in children presenting with mild to moderate acute asthma. DESIGN: A before-after comparison of children with acute asthma presenting to the emergency department (ED) between August and October 1999 with those presenting between June and August 1997. SETTING: A tertiary care metropolitan children's hospital. INTERVENTIONS: Evidence-based clinical practice guidelines for using spacers were developed by a local multidisciplinary consensus process. A multifaceted guideline implementation program was used in 1999. MAIN OUTCOME MEASURES: Physician prescribing practices (spacer use); clinical outcomes (need for hospitalisation, admission to intensive care unit, and length of stay [LOS]). RESULTS: 75 of 247 children (30%; 95% CI, 25%-36%) required hospital admission in 1999. This was similar to the 1997 study period, when 95 of 326 (29%; 95% CI, 24%-34%) children were admitted. Of those with mild to moderate asthma, 160 (68%) received bronchodilators in the ED; 151 (94%) were initially treated with a spacer device in 1999. In 1997, no children were initially treated with spacers in the ED. The median (range) LOS in hospital for children with asthma of all severities was 1.7 (0.5-19.8) days in 1999 and 1.7 (0.2-7.6) days in 1997 (P=0.85). CONCLUSIONS: We successfully changed standard practice from using nebulisers to spacers for bronchodilator delivery in children with mild to moderate acute asthma, with no difference in the need for or duration of hospitalisation.     

Serum anti-p53 antibodies in uterine and ovarian cancer: association with dna sequence copy number abnormalities.

The aim of the present study was to evaluate the clinical significance of the serum anti-p53 antibody in patients with uterine and ovarian cancer. Some of the ovarian patients were also evaluated for overexpression of p53 by immunohistochemistry and for cytogenetic alterations by comparative genomic hybridization (CGH). Serum anti-p53 antibodies were determined by an enzyme immunoassay kit. The antibody was detected in 8/30 (27%) of ovarian cancers, in 12/86 (14%) cancers of the uterine cervix, in 5/41 (12%) cancers of the uterine body, and 0/9 (0%) healthy women. The overall survival rate in patients with ovarian cancer was significantly worse in patients with anti-p53 antibody positivity than that in patients with anti-p53-antibody-negative cancers using the log rank test (p = 0.017). There was a significant correlation between the presence of anti-p53 antibody and tissue overexpression of p53 in ovarian cancers. CGH analysis showed that the aberrations in DNA sequence copy number in ovarian cancers were significantly increased in anti-p53-antibody-positive cases compared to antip53-antibody-negative cases including increased copy number on 20q and reduced copy number on 5q and 13q. Although the exact relationship between the presence of serum anti-p53 antibody (specific humoral response) and cytogenetic alterations is still unknown, these findings suggest that the measurement of serum anti-p53 antibody may be useful for the assessment of genetic instability and tumor biological aggressiveness.     

Involvement of long-chain acyl coenzyme A for lipid synthesis in repression of acetyl-coenzyme A carboxylase in Candida lipolytica.

Mutant strains of Candida lipolytica defective in acyl-CoA synthetase II [acid:CoA ligase (AMP-forming), EC 6.2.1.3] have been isolated. The mutants fail to grow on fatty acid as a sole carbon source but are capable of incorporating exogenous fatty acid into cellular lipids. This observation, together with our previous finding that mutant strains defective in acyl-CoA synthetase I cannot incorporate exogenous fatty acid into cellular lipids but are able to degrade fatty acid via beta-oxidation, indicates the presence of two functionally distinct long-chain acyl-CoA pools in the cell--i.e., one for lipid synthesis and the other for beta-oxidation. Unlike the wild-type and the revertant strains as well as the mutants lacking acyl-CoA synthetase II, the mutants defective in acyl-CoA synthetase I do not exhibit the repression of acetyl-CoA carboxylase [acetyl-CoA:carbon-dioxide ligase (ADP-forming), EC 6.4.1.2] by exogenous fatty acid. Measurement of the two long-chain acyl-CoA pools with the aid of appropriate mutant strains has indicated that the long-chain acyl-CoA to be utilized for lipid synthesis, but not that to be degraded via beta-oxidation, is involved in the repression of acetyl-CoA carboxylase.