How reliable is assessment of true vocal cord-arytenoid unit mobility in patients affected by laryngeal cancer? a multi-institutional study on 366 patients from the ARYFIX collaborative group.

PURPOSE: In clinical practice the assessment of the "vocal cord-arytenoid unit" (VCAU) mobility is crucial in the staging, prognosis, and choice of treatment of laryngeal squamous cell carcinoma (LSCC). The aim of the present study was to measure repeatability and reliability of clinical assessment of VCAU mobility and radiologic analysis of posterior laryngeal extension. METHODS: In this multi-institutional retrospective study, patients with LSCC-induced impairment of VCAU mobility who received curative treatment were included; pre-treatment endoscopy and contrast-enhanced imaging were collected and evaluated by raters. According to their evaluations, concordance, number of assigned categories, and inter- and intra-rater agreement were calculated. RESULTS: Twenty-two otorhinolaryngologists evaluated 366 videolaryngoscopies (total evaluations: 2170) and 6 radiologists evaluated 237 imaging studies (total evaluations: 477). The concordance of clinical rating was excellent in only 22.7% of cases. Overall, inter- and intra-rater agreement was weak. Supraglottic cancers and transoral endoscopy were associated with the lowest inter-observer reliability values. Radiologic inter-rater agreement was low and did not vary with imaging technique. Intra-rater reliability of radiologic evaluation was optimal. CONCLUSIONS: The current methods to assess VCAU mobility and posterior extension of LSCC are flawed by weak inter-observer agreement and reliability. Radiologic evaluation was characterized by very high intra-rater agreement, but weak inter-observer reliability. The relevance of VCAU mobility assessment in laryngeal oncology should be re-weighted. Patients affected by LSCC requiring imaging should be referred to dedicated radiologists with experience in head and neck oncology.

Pharmacokinetics and microdistribution of polyethylene glycol-modified humanized A33 antibody targeting colon cancer xenografts.

Therapeutic proteins have been conjugated with polyethylene glycol (PEGylation) to reduce immunogenicity and enhance circulating dose. Here we have investigated the effect of PEGylation on immunogenicity, pharmacokinetics, and histologic microdistribution of tumor-targeting antibodies with humanized A33 antibody (huA33) as a model system. Conjugation of huA33 with methoxy-PEG of M(r) 5,000 (32%-34% of primary amines modified) or M(r) 20,000 (16%-18% modification) preserved >50% of native huA33 binding to SW1222 colon cancer cells. In mice, both PEGylated forms cleared from serum moderately slower than native huA33. After repeated immunization with PEG-huA33, antiantibody titers in immunocompetent mice were <5% of those in huA33-treated controls. Both PEG-huA33 forms reached approx. 75% of the maximum tumor dose of huA33 in SW1222-xenografted mice, but their tumor:blood ratios were considerably reduced. To demonstrate immunologic specificity of PEG-huA33 targeting in SW1222 tumor-bearing mice, antigenic sites were presaturated by injecting excess native huA33. This reduced subsequent uptake of PEG-huA33 by up to 80%, whereas presaturation with hu3S193 control antibody had no significant effect. To assess the microdistribution of antibody uptake in the same xenograft model, tumor tissue resected at different time points after antibody administration was examined for human IgG by immunohistochemistry. Both PEG preparations achieved the same peak staining intensity and homogeneity as native huA33 with a delay of several hours. Given the measured reduction in immunoreactivity in vitro, these results demonstrate that the tumor targeting potential of huA33 in vivo is preserved at PEGylation levels sufficient to suppress immunogenicity.

Malignant transformation of an ovarian mature cystic teratoma presenting as a rectal mass.

BACKGROUND: Squamous cell carcinoma arising from malignant degeneration of a mature cystic teratoma is rare with a reported incidence of approximately 1-3%. The most common presenting symptoms are lower abdominal pain and increasing abdominal girth of several months' duration. Approximately 50% of the patients present with FIGO stage I while 35-38% present with stage III diseases. CASE: The case described herein represents an unusual presentation and initial diagnostic dilemma of locally aggressive squamous cell carcinoma arising in an ovarian dermoid cyst, with invasion into the distal rectum and anal canal causing rectal bleeding similar to the presentation of anal squamous cell carcinoma. Despite aggressive surgical management with posterior exenteration and optimal tumor debulking followed by 5040-cGy pelvic radiation utilizing 25-MV photons, the patient developed pelvic recurrence at the vaginal cuff 6 weeks after completion of her adjuvant radiotherapy. She subsequently failed cis-platinum single-agent chemotherapy and died 9 months after her initial surgery and diagnosis. CONCLUSION: Squamous cell carcinoma in the anal canal, diagnosed by colonoscopy or proctoscopy, could be an unusual presentation of that arising from malignant degeneration of an ovarian dermoid cyst. This tumor may behave in a locally aggressive manner and be resistant to pelvic radiation or single-agent chemotherapy of cis-platinum. The current experience of adjuvant treatment after comprehensive staging and cytoreductive surgery reported in the world literature is limited, and the optimal management of the malignancy remains unclear.

Utilization of nicotine nasal spray in smoking cessation.

It is widely accepted that nicotine replacement therapy can help patients to quit smoking. Recent approval by the US Food and Drug Administration of a nicotine nasal spray gives clinicians greater flexibility in choosing the best replacement therapy for a particular patient. Four types of smoking cessation therapy are currently available (gum, patch, nasal spray, and bupropion). These differ with respect to their onset and duration of action, adverse effects, and cost. This article focuses on which patients may benefit most from the use of nicotine nasal spray. Instructions for proper administration and dosing of the nicotine nasal spray are discussed as well as how to taper it appropriately, and how to avoid--and manage--adverse effects. Additionally, the cost of the nicotine nasal spray is reviewed and compared with over-the-counter products and bupropion. Resources for behavioral support are provided as well.

Use of transdermal nicotine systems in a possible suicide attempt.

BACKGROUND: Transdermal drug delivery systems, a relatively recent development, are well accepted by physicians and patients because of reliability and ease of administration. The patch reservoirs, however, contain large quantities of drug, and the potential for considerable toxicity exists if they are used incorrectly. A case is presented of an apparent suicide attempt that involved the use of nicotine transdermal patches. METHODS: This case report involved a patient seen in the emergency department by one of the authors. Data were obtained from the patient's medical record while maintaining confidentiality. RESULTS: The drug overdose was a potentially serious one. The patient recovered fully after an uneventful hospital course. CONCLUSIONS: Transdermal drug delivery systems now deliver many drugs, several of which are quite potent. Intentional or unintentional misuse of the systems can result in toxicity. The physician and pharmacist should carefully instruct each patient in the appropriate use and handling of transdermal drug delivery systems.

Do tobacco companies avoid proper use of warnings in magazine ads?

By law, cigarette advertisements in magazines must contain one of four surgeon general's warnings and these warnings must be rotated quarterly. This study surveyed the top 13 magazines by paid subscription in the United States that accept cigarette advertising to determine if cigarette companies are compliant with this law. All issues of these magazines published during 1990 were surveyed yielding 1329 ads. Goodness of fit chi-square was used to compare observed distributions of each warning with the expected distribution. There were no significant differences in the number of times each warning appeared over the year or in each magazine. The tobacco industry as a whole appears to follow the guidelines of the Comprehensive Smoking Education Act, though 2 of 6 companies and 8 of 32 brands appear to advertise more heavily when using certain warnings and less heavily when other warnings are utilized.