Authors Jan L. Brozek, MD, PhD – Department of Clinical Epidemiology & Biostatistics and Medicine, McMaster University, Hamilton, Canada Jean Bousquet, MD, PhD – Service des Maladies Respiratoires, Hopital Arnaud de Villeneuve, Montpellier, France, INSERM, CESP U1018, Respiratory and Environmental Epidemiology Team, France, and WHO Collaborating Center for Rhinitis and Asthma Carlos E. Baena-Cagnani, MD – Faculty of Medicine, Catholic University of Cordoba, Cordoba, Argentina Sergio Bonini, MD – Institute of Neurobiology and Molecular Medicine – CNR, Rome, Italy and Department of Medicine, Second University of Naples, Naples, Italy G. Walter Canonica, MD – Allergy & Respiratory Diseases, DIMI, Department of Internal Medicine, University of Genoa, Genoa, Italy Thomas B. Casale, MD – Division of Allergy and Immunology, Department of Medicine, Creighton University, Omaha, Nebraska, USA Roy Gerth van Wijk, MD, PhD – Section of Allergology, Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands Ken Ohta, MD, PhD – Division of Respiratory Medicine and Allergology, Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan Torsten Zuberbier, MD – Department of Dermatology and Allergy, Charite Universitatsmedizin Berlin, Berlin, Germany Holger J. Schunemann, MD, PhD, MSc – Department of Clinical Epidemiology & Biostatistics and Medicine, McMaster University, Hamilton, Canada

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Allergic Rhinitis and Its Impact on Asthma

Epidermal growth factor-related peptides and their receptors in human malignancies

Ventilator-associated pneumonia (VAP) continues to complicate the course of 8 to 28% of patients receiving mechanical ventilation (MV). In contrast to infections of more frequently involved organs (e.g., urinary tract and skin), for which mortality is low, ranging from 1 to 4%, the mortality rate for VAP ranges from 24 to 50% and can reach 76% in some specific settings or when lung infection is caused by high-risk pathogens. The predominant organisms responsible for infection are Staphylococcus aureus, Pseudomonas aeruginosa, and Enterobacteriaceae, but etiologic agents widely differ according to the population of patients in an intensive care unit, duration of hospital stay, and prior antimicrobial therapy. Because appropriate antimicrobial treatment of patients with VAP significantly improves outcome, more rapid identification of infected patients and accurate selection of antimicrobial agents represent important clinical goals. Our personal bias is that using bronchoscopic techniques to obtain protected brush and bronchoalveolar lavage specimens from the affected area in the lung permits physicians to devise a therapeutic strategy that is superior to one based only on clinical evaluation. When fiberoptic bronchoscopy is not available to physicians treating patients clinically suspected of having VAP, we recommend using either a simplified nonbronchoscopic diagnostic procedure or following a strategy in which decisions regarding antibiotic therapy are based on a clinical score constructed from seven variables. Selection of the initial antimicrobial therapy should be based on predominant flora responsible for VAP at each institution, clinical setting, information provided by direct examination of pulmonary secretions, and intrinsic antibacterial activities of antimicrobial agents and their pharmacokinetic characteristics. Further trials will be needed to clarify the optimal duration of treatment and the circumstances in which monotherapy can be safely used.

Ventilator-associated pneumonia.

Background Patients with head-and-neck cancers who are free of disease after local therapy remain at high risk for both recurrent and second primary tumors Retinoids have proved efficacious in the treatment of premalignant oral lesions and are promising agents for the prevention of epithelial carcinogenesis Methods We prospectively studied 103 patients who were disease-free after primary treatment for squamous-cell cancers of the larynx, pharynx, or oral cavity After completion of surgery or radiotherapy (or both), these patients were randomly assigned to receive either isotretinoin (13-cis-retinoic acid) (50 to 100 mg per square meter of body-surface area per day) or placebo, to be taken daily for 12 months Results There were no significant differences between the two groups in the number of local, regional, or distant recurrences of the primary cancers However, the isotretinoin group had significantly fewer second primary tumors After a median follow-up of 32 months, only 2 patients (4

https://www.nejm.org/doi/pdf/10.1056/NEJM199009203231205

Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck.

Metallothioneins (MTs) are intracellular, low molecular, low molecular weight, cysteine-rich proteins. Ubiquitous in eukaryotes, MTs have unique structural characteristics to give potent metal-binding and redox capabilities. A primary role has not been identified, and remains elusive, as further functions continue to be discovered. The most widely expressed isoforms in mammals, MT-1 and MT-2, are rapidly induced in the liver by a wide range of metals, drugs and inflammatory mediators. In teh gut and pancreas, MT responds mainly to Zn status. A brain isoform, MT-3, has a specific neuronal growth inhibitory activity, while MT-1 and MT-2 have more diverse functions related to their thiolate cluster structure. These include involvement in Zn homeostasis, protection against heavy metal (especially Cd) and oxidant damage, and metabolic regulation via Zn donation, sequestration and/or redox control. Use of mice with altered gene expression has enhance our understanding of the multifaceted role of MT, emphasised in this review.

Metallothionein: the multipurpose protein

Photo-oxidative disruption of lysosomal membranes causes apoptosis of cultured human fibroblasts

Comparison of reported series of laryngeal lesions is complicated by the inconsistency in the terminology. The classification of these lesions should logically be based on the degrees of dysplasia, as this has a bearing on the prognosis. The material for this study consisted of 193 patients with hyperplasia and/or keratosis, with or without mild dysplasia (Group I), moderate dysplasia (Group II), and severe dysplasia and carcinoma in situ (Group III). They were treated over a 14-year period (1966-1979) at Linkoping University Hospital. Of the 98 patients in Group I available for follow-up, 23 had repeat excisions. Moderate dysplasia developed in 3 patients, severe dysplasia in 2, and invasive carcinoma in another 2 within 3 and 3.5 years; they both underwent laryngectomy. Among the 24 patients in Group II available for follow-up, severe dysplasia developed in 3 and invasive carcinoma in 3 up to 13 years after the initial diagnosis, all but one (with severe dysplasia) received a full course of radiotherapy, on one case total laryngectomy was subsequently performed for recurrent carcinoma. Of the 39 patients with severe dysplasia and carcinoma in situ 16 were given primary radiotherapy; 4 of these developed invasive carcinoma; 3 of them underwent total laryngectomy and one partial laryngectomy. Excision or stripping of the vocal cords was the primary treatment in 23 cases; 5 of these developed invasive carcinoma; 2 of them underwent total laryngectomy. Diffuse lesions and well differentiated forms of severe dysplasia caused most problems and had the highest incidence of invasive carcinoma irrespective of the form of treatment. Patients with hyperplasia, keratosis, dysplasia and carcinoma in situ should be carefully followed up, as invasive carcinoma may develop many years after the initial diagnosis.

Hyperplasia, keratosis, dysplasia and carcinoma in situ of the vocal cords—a follow-up study

Adenocarcinoma makes up only a small percent of all nasal and paranasal sinus carcinomas, and is most often found in the ethmoid sinuses. Adenocarcinoma of the ethmoid sinuses is known to be associated with exposure to wood dust. Twenty-eight patients with ethmoid adenocarcinomas were collected, mainly during the last decade from a region with approximately 900,000 inhabitants and with a large amount of furniture industries. There were 4 women and 24 men in the study. Twenty of the men were exposed to dust from hardwood for 20 to 55 years (mean, 40 years) which is in accord with other reports and supports data on the increased risk for workers of developing adenocarcinoma of the ethmoid sinuses when exposed to dust from hardwood. Radiologic diagnosis is necessary to delineate the extent of these tumours, and computerized tomography (CT) especially furnishes important information. Most patients received preoperative radiotherapy followed by surgery, 50% of them survived 5 years, which is in accord with other reports.

Adenocarcinoma of the ethmoid sinuses. A review of 28 cases with special reference to wood dust exposure.

Aims

To validate histological criteria for the grading of epithelial hyperplastic laryngeal lesions (EHHL) (dysplastic laryngeal lesions), we used a system that had been devised and tested in Ljubljana, Slovenia over many years and was felt to be more appropriate to laryngeal pathology than is the commonly-used model of intraepithelial neoplasia in the cervix.



Methods and results

Vocal cord biopsies of 45 patients with a broad spectrum of EHLL were reviewed. Detailed histological criteria were formulated for each of the four grades of EHLL in the Ljubljana classification, comprising simple hyperplasia (benign spinous layer augmentation), abnormal hyperplasia (benign basal and parabasal layer augmentation), atypical hyperplasia (risky for malignancy) and carcinoma in situ (actually malignant, but without invasion).



Conclusions

Using these criteria a high degree of concordance of histological diagnoses of grading levels for the Ljubljana classification was achieved between the pathologists of the Working Group. The system was found to be more precise for routine diagnostic work than the others in vogue. The different grades of the Ljubljana classification correspond to significantly different levels yielded in each grade by the semi-objective methods of quantitative morphometry and immunohistochemistry.

Criteria for grading in the Ljubljana classification of epithelial hyperplastic laryngeal lesions. A study by members of the Working Group on Epithelial Hyperplastic Laryngeal Lesions of the European Society of Pathology

The clinicopathological and immunocytochemical features of nine cases of salivary duct carcinoma are described. This relatively rare tumour, which only recently has been widely recognized as a separate entity, is highly malignant and caused the death in eight of the patients. The tumour cells are arranged in cribriform and solid growth patterns, where the solid tumour nests frequently have comedo necrosis, and a fibrous, often sclerotic, stroma is present. The infiltrating desmoplasmic component and the diffuse invasive growth into adjacent adipose parotid tissue have similarities to ductal breast carcinoma. Immunocytochemical investigation of salivary duct carcinoma showed constant overexpression of c-erbB-2 as detected by membrane accentuation, and high proliferative activity as detected by nuclear positivity for MIB 1 (Ki-67). Changes in the expression of p53 and retinoblastoma gene product do not constitute a constant event in salivary duct carcinoma. A few of the tumours showed scattered cells with distinct nuclear positivity for both progesterone and oestrogen receptors. We emphasize that this highly malignant salivary gland tumour has a characteristic morphology, may not be as rare as previously considered, and that prompt and aggressive therapy is needed.

Henrik B. Hellquist

Papers

Photo-oxidative disruption of lysosomal membranes causes apoptosis of cultured human fibroblasts

Hyperplasia, keratosis, dysplasia and carcinoma in situ of the vocal cords—a follow-up study

Adenocarcinoma of the ethmoid sinuses. A review of 28 cases with special reference to wood dust exposure.

Criteria for grading in the Ljubljana classification of epithelial hyperplastic laryngeal lesions. A study by members of the Working Group on Epithelial Hyperplastic Laryngeal Lesions of the European Society of Pathology

Salivary duct carcinoma : a highly aggressive salivary gland tumour with overexpression of c-erbB-2