Carlos Suárez

First Detection of the Plasmid-Mediated Class A Carbapenemase KPC-2 in Clinical Isolates of Klebsiella pneumoniae from South America

ABSTRACT The plasmid-mediated class A carbapenemase KPC-2 was isolated from unrelated Klebsiella pneumoniae isolates in Medellin, Colombia. These KPC enzymes are the first from South America and the second isolation outside of the United States. The expanding geographic spread of KPC carbapenemases underscores the importance of clinical recognition of these enzymes.

Genetic polymorphism of N-acetyltransferase-2, glutathione S-transferase-M1, and cytochromes P450IIE1 and P450IID6 in the susceptibility to head and neck cancer.

AIMS: To analyse the allele frequencies of DNA polymorphisms at the genes for cytochromes P450IIE1 and P450IID6, N-acetyltransferase-2, and glutathione S-transferase-M1 in patients with head and neck squamous cell carcinoma, in an attempt to define genetic factors involved in the susceptibility to this cancer, which is strongly associated with tobacco consumption. METHODS: Determination of restriction fragment length polymorphism (RFLP) at cytochromes P450IIE1/P450IID6 and NAT2 genes, and the presence of homozygous deletion of the GSTM1 gene, in 200 controls and 75 head and neck cancer patients. Allelic frequencies between the two groups were compared using a chi 2 test, and odds ratio with 95% confidence intervals were calculated. RESULTS: There was no evidence of an association between alleles of CYP2D6 and CYP2E1 and head and neck cancer in our population. Similarly, frequencies of individuals lacking the GSTM1 gene did not differ between controls and patients. However, individuals with the NAT2-SA phenotype were at higher risk of developing head and neck cancer. The frequencies of the most common SA genotype (homozygous for the NAT2*5 allele) were higher in patients than in controls (27% v 15%, respectively). Slow acetylators homozygous for the NAT2*6 allele, the second most common SA allele, were also more common in patients than in controls (11% v 5%, respectively). CONCLUSIONS: Slow NAT2 activity is a risk factor possibly leading to the development of head and neck cancer in response to tobacco carcinogens.

Prognostic factors in paranasal sinus cancer

PURPOSE This study was designed to evaluate the influence of several different prognostic factors in determining both local recurrence rates and survival in patients treated for carcinoma of the paranasal sinuses. MATERIALS AND METHODS A retrospective study of patients treated between January, 1975 and December, 1991 was undertaken. Hospital charts were reviewed collecting demographic, clinical, and radiographic findings, which were correlated with treatment and subsequent follow-up. RESULTS Carcinoma of the paranasal sinuses was identified in 129 patients. This included 95 men and 34 women with an average of 59 years. The ethmoid sinus was primarily involved in 50 patients, the maxillary sinus and 49, the nasal sinus and 25, sphenoid sinus in three in the frontal sinus and two patients. Advanced stage (T3/T4) was diagnosed in 60% of patients at presentation. The most commonly encountered histologies were squamous-cell carcinoma and adenocarcinoma. The most accurate predictors of poor prognosis were advanced T stage and involvement of the anterior skill base. Involvement of the posterior wall of the maxillary sinus, infratemporal fossa, and erosion of the orbital wall was not associated with the worst prognosis. CONCLUSION In spite of advances in imaging technique and surgical therapy, the primary cause of death is inability to control local disease. Diagnosis at an earlier stage is associated with improved outcome.

Overexpression of Focal Adhesion Kinase in Head and Neck Squamous Cell Carcinoma Is Independent of fak Gene Copy Number

The development of human malignancies can involve the aberrant regulation of intracellular signal transduction pathways that regulate cell-extracellular matrix interactions. Purpose: In the current study, we aimed to evaluate focal adhesion kinase (FAK) at both genetic and protein expression levels in head and neck squamous cell carcinomas (HNSCC) and to explore the prognostic significance of FAK. Experimental Design: A total of 211 tissue specimens, including 147 primary tumors, 56 lymph node metastases, 3 benign hyperplasias, and 5 dysplasias, were analyzed using immunohistochemistry. The fak gene dosage was determined in 33 tumors. Correlations among DNA, protein, and clinicopathologic variables were analyzed. Results: FAK protein was overexpressed in HNSCCs compared with corresponding normal mucosa. High expression levels were found in 62% of the samples. Positive immunostaining was also detected in benign hyperplasias and preinvasive dysplastic lesions. All lymph node metastases examined showed FAK overexpression, with significant correlation with the expression in matched primary tumor. DNA copy number ratios for fak were higher in 39% of the tumors compared with normal mucosa. However, elevated FAK expression did not correlate with gains on DNA level, and not all cases with an amplification of the fak gene displayed protein overexpression. Similar data were obtained in five HNSCC-derived cell lines, in which FAK mRNA levels were precisely correlated with FAK protein levels. FAK protein overexpression in tumors correlated with nodal metastases. Conclusions: These findings suggest an involvement of FAK in the onset and progression of HNSCC and provide an insight into a mechanism of FAK activation alternative to gene amplification.

NECK TREATMENT AND SHOULDER MORBIDITY: STILL A CHALLENGE

Shoulder complaints and functional impairment are common sequelae of neck dissection. This is often attributed to injury of the spinal accessory nerve by dissection or direct trauma. Nevertheless, shoulder morbidity may also occur in cases in which the spinal accessory nerve has been preserved. In this article, the physiology and pathophysiology of the shoulder are discussed, followed by a consideration of the impact of neck dissection on shoulder complaints, functional impairment, and quality of life. Finally, rehabilitation will be considered.

Primary treatment of the anterior vocal commissure squamous carcinoma

Squamous cell carcinoma may involve the anterior commissure (AC) area of the laryngeal glottis, and can be grouped morphologically into four groups; (1) tumor confined to the AC, (2) tumor involving one cord and the AC, (3) tumor involving the AC and a portion of both vocal cords, and (4) tumor involving a greater part of one cord and crossing over to involve a variable length of the other cord. Some of these patients when evaluated by imaging, either CT and/or MRI, may demonstrate thyroid cartilage erosion or involvement, thereby upstaging a T1a, T1b into a T3 or a T4 glottic cancer. The majority of patients treated by radiotherapy have only been staged clinically, and hence a failure or recurrence rate of 15%. In patients treated surgically by endoscopic or external surgery, the local recurrence rates are similar at 15%. Therefore, future reporting of patients treated with AC involvement should be staged radiologically, to include CT or MRI, and documentation of the treatment results be reported in subgroups, according to whether there is no cartilage involvement, inner-table cartilage erosion, or through-and-through cartilage invasion. Should endoscopic cordectomy be used, then the type of surgery performed should be based on the classification as suggested by the European Laryngological Society. The use of the above recommendations would allow for more meaningful results to be reported and for cause specific analysis of failure of treatment techniques applied.

Functional outcomes of transoral laser surgery of supraglottic carcinoma compared with a transcervical approach: Transoral Versus Transcervical Supraglottic Laryngectomy

Several functional advantages have been described for the transoral laser supraglottic laryngectomy as compared with open techniques. However, comparative studies have been rarely performed.

Sinonasal carcinoma: clinical, pathological, genetic and therapeutic advances

The sinonasal cavities represent an anatomical region affected by a variety of tumours with clinical, aetiological, pathological, and genetic features distinct from tumours at the main head and neck cancer localizations. Together, squamous-cell carcinoma and adenocarcinoma account for 80% of all sinonasal tumours, and are aetiologically associated with professional exposure to wood and leather dust particles and other industrial compounds, and therefore, are officially recognized as an occupational disease. Owing to their distinctive characteristics, sinonasal tumours should be considered as separate entities, not to be included in the miscellany of head and neck cancers. Sinonasal tumours are rare, with an annual incidence of approximately 1 case per 100,000 inhabitants worldwide, a fact that has hampered molecular-genetic studies of the tumorigenic pathways and the testing of alternative treatment strategies. Nevertheless, the clinical management of sinonasal cancer has improved owing to advances in imaging techniques, endoscopic surgical approaches, and radiotherapy. Genetic profiling and the development of in vitro cell lines and animal models currently form the basis for future targeted anticancer therapies. We review these advances in our understanding and treatment of sinonasal tumours.

Next-Generation Sequencing for Infectious Disease Diagnosis and Management: A Report of the Association for Molecular Pathology

Next-generation sequencing (NGS) technologies are increasingly being used for diagnosis and monitoring of infectious diseases. Herein, we review the application of NGS in clinical microbiology, focusing on genotypic resistance testing, direct detection of unknown disease-associated pathogens in clinical specimens, investigation of microbial population diversity in the human host, and strain typing. We have organized the review into three main sections: i) applications in clinical virology, ii) applications in clinical bacteriology, mycobacteriology, and mycology, and iii) validation, quality control, and maintenance of proficiency. Although NGS holds enormous promise for clinical infectious disease testing, many challenges remain, including automation, standardizing technical protocols and bioinformatics pipelines, improving reference databases, establishing proficiency testing and quality control measures, and reducing cost and turnaround time, all of which would be necessary for widespread adoption of NGS in clinical microbiology laboratories.

Neck dissection with or without postoperative radiotherapy in supraglottic carcinomas.

A retrospective review of 302 previously untreated patients with primary supraglottic carcinoma was undertaken to ascertain the efficacy of postoperative radiotherapy. The 302 patients underwent a total of 383 functional neck dissections and 45 classic radical neck dissections. Pathological examination revealed nodal involvement in 117 patients (39%). In the histologically N0 group, the incidence of contralateral neck recurrence when a unilateral neck dissection and postoperative radiotherapy were carried out was 8%, rising 21% when no postoperative radiation was given. There was no difference in the ipsilateral recurrence rate in the N0 group, radiated patients (3%) and nonradiated patients (2%). Similar figures were found in the N1 group. Bilateral functional neck dissection in histologically N0, N1, and N2 necks had similar recurrence rates with or without radiotherapy. Distant metastasis appeared in 10% of N0 patients and in 35% of N3 patients. Patients who received postoperative radiotherapy showed a significantly higher rate of distant metastasis (21%) than patients who did not (8%). The number of involved lymph nodes had no relevance both in neck recurrence and distant metastasis.