Treatment considerations for head and neck cancer in the elderly

As life expectancy increases, surgeons can expect an increasing number of geriatric patients. In turn, the number of elderly patients presenting with head and neck cancer is likely to increase. Management of this subpopulation has become a source of debate because there is a paucity of randomized data regarding the effect of age on treatment response and morbidity associated with the treatment of head and neck cancer. The management of head and neck cancer in the elderly depends on the patient's age and general condition, the stage of disease, the effects of treatment on quality of life (such as speech and swallowing), patient and family wishes, and active physician participation in continued care. Elderly patient's comorbid conditions need appropriate attention especially if surgery is to be undertaken. The aim of this review is to examine the current literature in an attempt to develop an approach to the treatment of the elderly patient with head and neck cancer and to define the pertinent issues that require further study.     

Reepithelialized orthotopic tracheal allografts expand memory cytotoxic T lymphocytes but show no evidence of chronic rejection

BACKGROUND: Acute rejection of mouse tracheal allografts is characterized by infiltration of the lamina propria with CD4+/CD8+ T cells that leads to the destruction of the epithelium and luminal obliteration. The donor epithelium is progressively replaced by recipient-derived epithelium. Once allograft reepithelialization has occurred, immunosuppression can be withdrawn without inciting acute rejection. We hypothesize that reepithelialization will also prevent chronic rejection of the trachea after withdrawal of immunosuppression. METHODS: BALB/c tracheal grafts were transplanted orthotopically into allogeneic C57BL/6 recipients. Allografted mice were nonimmunosuppressed for 10 or 100 days or immunosuppressed with cyclosporine A continuously for 50 days and then withdrawn from immunosuppression for an additional 50 days. In addition, grafts from this group were then heterotopically retransplanted into isogenic C57BL/6 or allogeneic BALB/c recipients to assess their immunogenicity. RESULTS: Cyclosporine A-treated mice showed no signs of chronic rejection or priming of cellular immunity as measured by proliferation and cytokine secretion in a mixed leukocyte reaction. However, there was a notable expansion of memory CD8+ T cells specific for donor major histocompatibility complex. When these tracheal allografts were retransplanted heterotopically into C57BL/6 or BALB/c, they demonstrated reduced responses toward BALB/c and primed responses toward C57BL/6, respectively. These results suggest that the grafts express a chimeric phenotype consisting of both BALB/c and C57BL/6 antigens. CONCLUSION: These observations suggest that long-term withdrawal of immunosuppression does not lead to chronic tracheal rejection even in the presence of alloantigen specific cytotoxic T-lymphocyte responses and that the reepithelialized grafts may contain donor elements that impact the generation of immunity.     

The influence of intraoperative parathyroid hormone monitoring on the surgical management of hyperparathyroidism.

OBJECTIVE: To examine the role of intraoperative rapid parathyroid hormone (PTH) monitoring in the surgical management of hyperparathyroidism. DESIGN: Thirty-eight-month retrospective review. SETTING: Tertiary care academic medical center. PATIENTS: One hundred consecutive patients undergoing surgery for primary hyperparathyroidism. INTERVENTION: All patients underwent preoperative technetium Tc 99m sestamibi scan localization and intraoperative blood PTH monitoring by means of a rapid (12-minute) immunochemiluminometric assay. MAIN OUTCOME MEASURES: The influence of intraoperative PTH levels on extent of surgical dissection and achievement of postoperative normocalcemia. RESULTS: Intraoperative PTH levels dropped an average of 64%, 75%, and 83% at 5, 10, and 20 minutes, respectively, after excision of all hyperfunctioning parathyroid tissue. A PTH decrease of 46% or more at 10 minutes and 59% or more at 20 minutes after excision of hyperfunctioning tissue was predictive of postoperative normocalcemia. In 79 patients (79%), the sestamibi scan provided accurate preoperative localization; all but 1 of these patients were treated successfully, most often with a limited, gland-specific dissection. In 24 patients with inaccurate, negative, or misleading preoperative sestamibi scans, 23 (96%) were treated successfully with the use of the intraoperative PTH assay. CONCLUSIONS: The rapid intraoperative PTH assay accurately predicts postoperative success in patients with primary hyperparathyroidism. The rapid PTH assay allows for greater confidence in performing limited dissections in well-localized uniglandular disease. In cases of inaccurate preoperative localization, the rapid PTH assay directly affects surgical decision making and provides greater confidence in determining when surgical success has been achieved.     

Immunohistochemical detection of X-linked inhibitor of apoptosis in head and neck squamous cell carcinoma

The X-linked inhibitor of apoptosis (XIAP) is the most potent member of the IAP group of structurally related caspase inhibitors. Experimental and clinical evidence implicates XIAP in resistance to cancer therapy and in clinical aggressiveness of certain tumors. We examined the expression of XIAP in head and neck squamous cell carcinoma (SCC). Four-micrometer sections from 59 routinely processed specimens of head and neck SCC were subjected to citrate-based antigen retrieval, followed by incubation with monoclonal anti-XIAP antibody (BD Biosciences, San Jose, Calif) and EnVision Plus reagents (Dako, Carpinteria, Calif). Granular cytoplasmic staining was considered positive; the extent and intensity of staining were recorded. Normal squamous epithelium was either nonstaining (n=22), displayed generally weak basal staining (n=9), or moderate basal staining (n=1). Squamous dysplasia or carcinoma in situ was either nonstaining (10 of 18 cases) or displayed generally weak staining (8 of 18 cases). Varying degrees of XIAP positivity were found in 41 (69.5%) of 59 carcinomas. Most of the nonstaining and weakly staining carcinomas were well or moderately differentiated. In contrast, intense and extensive staining was most frequently found in poorly differentiated carcinomas. In keratinized tumor nests, staining was strongest peripherally and became diminished in central keratinized zones. New parameters of tumor aggressiveness are needed for more effective triaging of patients to appropriately aggressive therapies. The present findings suggest that the potent apoptotic inhibitor XIAP may be such a biomarker in head and neck SCCs, of resistance to apoptosis-inducing therapies, and, possibly, of responsiveness to a new class of XIAP-suppressive drugs presently in clinical trials for other malignancies or in preclinical development.     

Xanthones from Gentianella amarella ssp. acuta with acetylcholinesterase and monoamine oxidase inhibitory activities

Two new xanthone glycosides, corymbiferin 3-O-beta-D-glucopyranoside (1) and swertiabisxanthone-I 8'-O-beta- d-glucopyranoside (2), were isolated from Gentianella amarella ssp. acuta, along with eight known xanthones: triptexanthoside C, veratriloside, corymbiferin 1-O-glucoside, swertianolin, norswertianolin, swertiabisxanthone-I, bellidin, and bellidifolin, four of them identified for the first time in G. amarella ssp. acuta. The isolation was conducted mainly by centrifugal partition chromatography, and the structures of the isolated compounds were established on the basis of spectrometric data including 2D NMR and mass spectrometry. Xanthones were weakly active against acetylcholinesterase (AChE), except triptexanthoside C, which inhibited AChE with an IC(50) of 13.8 +/- 1.6 microM. Some compounds were active against monoamine oxidases (MAO): bellidin and bellidifolin showed interesting inhibitory activity of MAO A, while swertianolin, the 8-O-glucopyranoside form of bellidifolin, gave 93.6% inhibition of MAO B activity at 10(-5) M.     

Early Detection of Recurrent Disease by FDG‐PET/CT Leads to Management Changes in Patients With Squamous Cell Cancer of the Head and Neck

Objective.

The objective of this study was to compare the efficacy of surveillance high-resolution computed tomography (HRCT) and physical examination/endoscopy (PE/E) with the efficacy of fluorodeoxyglucose (FDG)-positron emission tomography (PET)/HRCT for the detection of relapse in head and neck squamous cell carcinoma (HNSCC) after primary treatment.

Methods.

This is a retrospective analysis of contemporaneously performed FDG-PET/HRCT, neck HRCT, and PE/E in 99 curatively treated patients with HNSCC during post-therapy surveillance to compare performance test characteristics in the detection of early recurrence or second primary cancer.

Results.

Relapse occurred in 19 of 99 patients (20%) during a median follow-up of 21 months (range: 9–52 months). Median time to first PET/HRCT was 3.5 months. The median time to radiological recurrence was 6 months (range: 2.3–32 months). FDG-PET/HRCT detected more disease recurrences or second primary cancers and did so earlier than HRCT or PE/E. The sensitivity, specificity, and positive and negative predictive values for detecting locoregional and distant recurrence or second primary cancer were 100%, 87.3%, 56.5%, and 100%, respectively, for PET/HRCT versus 61.5%, 94.9%, 66.7%, and 93.8%, respectively, for HRCT versus 23.1%, 98.7%, 75%, and 88.6%, respectively, for PE/E. In 19 patients with true positive PET/HRCT findings, a significant change in the management of disease occurred, prompting either salvage or systemic therapy. Of the 14 curatively treated patients, 11 were alive with without disease at a median follow-up of 31.5 months.

Conclusion.

FDG-PET/HRCT has a high sensitivity in the early detection of relapse or second primary cancer in patients with HNSCC, with significant management implications. Given improvements in therapy and changes in HNSCC biology, appropriate modifications in current post-therapy surveillance may be required to determine effective salvage or definitive therapies.     

Role of Toll-like Receptor 3 Variants in Aspirin-Exacerbated Respiratory Disease

Purpose

Although the mechanism of virus-induced, aspirin-exacerbated respiratory disease (AERD) is not known fully, direct activation of viral components through Toll-like receptor 3 (TLR3) has been suggested. TLR3 recognizes double-stranded RNA (dsRNA), and activates nuclear factor-κB and increases interferon-γ, which signals other cells to induce airway inflammation in asthma. Considering the association of TLR3 in viral infections and AERD, we investigated whether promoter and non-synonymous variants of TLR3 were associated with AERD.

Methods

The three study groups, 203 with AERD, 254 with aspirin-tolerant asthma (ATA), and 274 normal healthy controls (NC) were recruited from Ajou University Hospital, Korea. Two polymorphisms, -299698G>T and 293391G>A [Leu412Phe], were genotyped using primer extension methods.

Results

Genetic associations were examined between two genetic polymorphisms of TLR3 (-299698G>T and 293391G>A [Leu412Phe]) in the three study groups. AERD patients that carried the GG genotype of 293391G>A showed a significantly lower frequency compared with ATA in both co-dominant (P=0.025) and dominant models (P=0.036). Similarly, in the minor allele frequency, the A allele was significantly higher (P=0.023) in AERD compared with ATA for this polymorphism. AERD patients who carried HT2 [GA] showed a significantly higher frequency than other haplotypes in co-dominant (P=0.02) and recessive (P=0.026) models.

Conclusions

Our findings suggest that the -299698G>T and 293391G>A [Leu412Phe] polymorphisms of the TLR3 gene are associated with the AERD phenotype.     

Syphilitic lymphadenitis diagnosed via fine needle aspiration biopsy

Syphilis is coming back in the recent a few decades especially in the gay and HIV populations. Since syphilis can be "the great mimic" clinically and pathologically, a case report with updated review can be helpful to the medical community. We report, a case of syphilitic lymphadenitis diagnosed via fine needle aspiration biopsy (FNAB). The pitfalls associated with the diagnosis of syphilitic lymphadenitis will be discussed. The patient's medical records were reviewed. The pertinent history, clinical course, and ancillary studies including FNAB cytology with special stains are presented. In addition to the case report, we discuss the diagnosis of syphilitic lymphadenitis and the role of FNAB cytology. This was a 37-year-old man presenting with a two-month history of a growing neck mass, night sweats, and a ten pound weight loss. The patient had been treated one month earlier for primary syphilis. Examination of the head and neck revealed a 3 cm right level II mass. FNAB cytology showed heterogeneous population of lymphocytes and plasma cells suggesting reactive changes. Modified silver staining of the cell block slide was performed and revealed spirochetes, consistent with syphilis. The patient's lymphadenitis resolved with a course of antibiotic treatment. Although lymphadenopathy is a rare presentation of syphilis, it should be included in the differential diagnosis for patients who offer a suspect history. FNAB with silver staining is an effective, minimally invasive way to confirm the diagnosis.