Staging of laryngeal cancer using 64-channel multidetector row CT: comparison of standard neck CT with dedicated breath-maneuver laryngeal CT.

BACKGROUND AND PURPOSE: With a 64-channel multidetector row CT, imaging acquisition during speech, swallowing, or phonation has become feasible. However, the actual benefit of these additional focused images should be critically evaluated with respect to radiation dose. The purpose of this study was to determine if dedicated laryngeal CT using breath-holding and straw-blowing improved the accuracy of TNM-staging for patients with biopsy-proved laryngeal carcinomas in comparison with a standard neck CT. MATERIALS AND METHODS: A total of 27 patients underwent a standard neck CT and a laryngeal CT with additional images acquired while patients held their breath or blew through a straw. Two radiologists interpreted the neck CT and later the laryngeal CT and assigned a TNM-stage for each case. These interpretations were compared with a TNM-stage determined by surgery and/or clinical examination for the individual patients. The accuracy of standard neck CT was compared with the accuracy of laryngeal CT. RESULTS: The overall accuracy was not significantly different between standard neck CT and the additional laryngeal CT and was, in fact, lower in cases with additional larynx images. The accuracy of staging was slightly improved with the additional laryngeal CT for glottic cancers; however, it was decreased for supraglottic cancers. The accuracy of a dichotomous diagnosis of early-versus-advanced-stage cancer was 0.86 for the standard neck CT and 0.80 for the laryngeal CT. The readers' confidence levels did not improve with the use of the additional images. CONCLUSIONS: In the era of isovoxel multidetector CT technology and judicious monitoring of radiation dose, a standard neck CT with coronal and sagittal reformats should suffice for the staging of laryngeal cancer.

Combined use of high-frequency jet ventilation and abdominal lift for laparoscopic cholecystectomy in a patient with glottic impairment.

Effective airway management during laparoscopic anesthesia is important to minimize the adverse consequences of the carbon dioxide (CO2) pneumoperitoneum (PP). During PP, reduced respiratory excursion and tidal volumes with increased CO2 absorption may lead to hypoxia, hypercapnia, and respiratory acidosis. Although these problems can usually be avoided by use of positive pressure ventilation and an endotracheal tube, patients with a restricted airway who cannot be intubated pose a unique challenge. High-frequency jet ventilation (HFJV) has been described as an alternative to endotracheal intubation in other settings. The use of the small-diameter jet tube allows relatively unobstructed access to the larynx during laryngeal surgery. In patients with glottic impairment related to vocal fold immobility, jet ventilation allows positive pressure ventilation without the use of an endotracheal tube or tracheostomy in cases where lung and diaphragmatic compliance permit adequate excursion for ventilation and glottal diameter permits an adequate outflow of air. In this report, we describe the successful use of HFJV combined with an abdominal lifting technique and low-pressure PP for laparoscopic surgery in a patient with glottic compromise related to vocal fold immobility. Using these techniques, a laparoscopic cholecystectomy was performed successfully without endotracheal intubation or the need for a tracheostomy.

Pharyngeal pH measurements in patients with respiratory symptoms before and during proton pump inhibitor therapy.

BACKGROUND: Pharyngeal pH monitoring is a diagnostic tool used to identify Gastroesophageal reflux disease (GERD) as an etiology of respiratory symptoms. We performed pharyngeal pH monitoring on 14 patients with respiratory symptoms thought to be induced by GERD. METHODS: Symptoms and pH monitoring (esophageal and pharyngeal) were assessed prior to and 3 months after the initiation of double-dose proton pump inhibitor therapy. RESULTS: Symptoms included cough, hoarseness, and throat clearing. Ten patients had at least one episode of pharyngeal reflux (PR+) and 4 patients had no pharyngeal reflux (PR-). Pharyngeal reflux episodes in PR+ patients decreased from 3.5 to 0.9 (P <0.05) per day with 8 of 10 (80%) patients having elimination or reduction of such episodes. Eight of 9 PR+ patients (89%) with suppressed pharyngeal reflux on medical therapy had resolution of respiratory symptoms. Three of 4 PR- patients (75%) had persistent symptoms on medical therapy. CONCLUSIONS: Proton pump inhibitor therapy improves clinical symptoms and decreases pharyngeal reflux episodes in patients with respiratory symptoms related to GERD. Direct measurement of pharyngeal pH is helpful in the identification of patients likely to respond to antireflux therapy.

Association of laryngopharyngeal reflux disease and subglottic stenosis.

Laryngopharyngeal reflux (LPR) disease and extraesophageal manifestations of gastroesophageal reflux have been recognized to have dramatic effects in the upper airways. Patient-reported symptoms alone underestimate the presence of LPR, making accurate clinical diagnosis difficult. Many previous studies examine populations with only standard dual-probe pH testing that does not include a test probe in the pharynx. Therefore, documentation of acid exposure at the laryngeal inlet is lacking. In adult patients with subglottic stenosis (SGS), whether due to granulomatous disease or presumed idiopathic causes, LPR is often a contributing or causative factor. A retrospective chart review from 1991 to 1999 identified 19 patients with SGS. Ten of the 19 patients had concomitant disease states, including sarcoidosis (3), Wegener's granulomatosis (3), laryngeal trauma (3), and a history of intubation (1). Fourteen patients underwent 24-hour ambulatory pH probe testing with 3- or 4-port probes. The proximal port in either catheter was positioned by manometric guidance directly behind the laryngeal inlet. Measurements of pH of less than 4 were recorded at the level of the larynx in 12 of the 14 patients tested (86%). This finding was noted in half of the patients despite empirical therapy with proton pump inhibitors at the time of the testing. Seven of 10 patients with underlying disease were studied, and all demonstrated acid reflux in the hypopharynx. In 9 patients, the stenosis was presumed to be idiopathic. Five of the 7 patients (71%) with idiopathic SGS tested had positive pH probe studies (pH below 4 in the pharyngeal probe). Our results demonstrate a strong association of LPR and SGS. In the idiopathic group, reflux is the probable cause of their stenosis. In the group of patients with underlying disease states, reflux was involved in all tested patients and likely acts as a synergistic factor that stimulates their granulomatous disease to react and subsequently result in the development of stenosis. Evaluation for LPR with pharyngeal pH testing should be performed in all patients with SGS.

Pharyngeal pH monitoring in 222 patients with suspected laryngeal reflux.

To determine the existence of and characterize gastroesophagopharyngeal reflux in patients with symptoms of airway irritation, we monitored pharyngeal pH over a 24-hour period in 222 consecutive patients. Pharyngeal reflux was defined as a drop in pH to less than 4 at the pharyngeal sensor, which occurred simultaneously with acidification of the distal esophagus. Patients were divided into two groups: those with pharyngeal reflux (PR+) and those without (PR-). The Mann-Whitney U test and Student's t test were used to assess intergroup comparisons. Episodes of pharyngeal reflux (range 1 to 36, average 4.4) were identified in 90 PR+ patients (40%). No pharyngeal reflux was identified in the remaining 132 patients (PR-). Episodes of pharyngeal reflux were rapidly cleared (average duration 1.5 minutes), and occurred while in the upright position in 77 (86%) of 90 patients and while in the supine position in 11 (12%) of 90 patients. Twenty-three patients (25%) experienced symptoms in association with an episode of pharyngeal reflux. In the distal esophagus, the percentage of time the pH was below 4 during the upright position and the total percentage of time the pH was below 4 were greater in PR+ patients (6.4% and 5.8%, respectively) when compared to PR- patients (2.6% and 2.6%, respectively). Laryngoscopic findings did not distinguish PR+ from PR- patients. Pharyngeal reflux occurs most commonly in the upright position and can be identified in more than 40% of patients thought to have acid-induced laryngeal symptoms. Even though these episodes are short lived and rapidly cleared, symptoms occur concomitantly in 25% of patients with proven pharyngeal reflux. Patients with laryngeal symptoms and documented pharyngeal reflux have greater amounts of esophageal reflux when compared to patients with laryngeal symptoms and no demonstrable pharyngeal reflux.

Importance of margin status in outcome of breast-conserving surgery for carcinoma.

BACKGROUND: The importance of margin status in breast-conserving therapy (BCT) for breast cancer remains unclear. We reviewed our experience with BCT to determine the risk of local recurrence as a function of margin status. METHODS: Stages I and II breast cancers treated with BCT between 1985 and 1990 were reviewed. Two hundred eleven patients were classified based on initial margin status: negative (more than 3 mm), close (3 mm or less), positive, or unknown. The incidence of reexcision and residual tumor is reported in each group. Patients with 36 months or more of follow-up (n = 183) were also stratified by final margin to examine rates of local recurrence and distant recurrence. RESULTS: Residual carcinoma was found in 0%, 24%, 44%, and 48% of the negative, close, positive, and unknown initial margin groups, respectively. The local recurrence rate was equivalent by Fisher exact test in patients with negative and close final margins (3%). The negative and close groups were not different by chi-squared analysis in terms of T stage, estrogen receptor status, and nodal status. CONCLUSIONS: Although one fourth of patients with close margins have residual tumor, recurrence rates are similar to those with negative margins. Reexcision of close margins is not necessary in patients who undergo BCT for carcinoma.

Cancer cachexia is transmissible in plasma.

The cause of cancer cachexia is unclear. Tumors may be competing with the host for ingested nutrients or may be releasing some factor that actively inhibits energy utilization. To explore these questions, plasma was sterilely collected and pooled from 103 terminally cachectic Fischer 344 rats implanted with an experimental sarcoma. Control plasma was collected in similar fashion from 138 nontumor-bearing rats (NTBP). Plasma from tumor-bearing rats (TBP) or NTBP was continuously infused in a randomized, blinded fashion for 4 days into 20 normal rats. During infusion, food intake and nitrogen excretion were measured daily. At sacrifice, body weight and organ masses were determined. Rats receiving TBP demonstrated an immediate and profound anorexia compared with those receiving NTBP. Total food intake during treatment was 31.2 +/- 3.3 (g +/- SEM) in the TBP group versus 48.2 +/- 2.8 in the NTBP group (P less than 0.001 by t test). Likewise, the total decline in body weight was greater in the TBP group as compared with the NTBP group (-35.2 +/- 3.4 versus -14.6 +/- 4.0, P less than 0.001). Mean daily nitrogen balance during treatment was negative in the rats receiving TBP (-14.5 +/- 20.1 mg +/- SEM) while remaining highly positive in the rats receiving NTBP (110.7 +/- 19.3, P less than 0.002). Finally, cardiac and gastrocnemius muscle masses were decreased, while hepatic mass was unaffected. These data demonstrate that the syndrome of cancer-associated cachexia is transmissible in plasma and therefore may be mediated by a circulating molecule or molecules. Identification and purification of the molecule(s) responsible for this effect would have obvious clinical benefits.

The effect of ketoconazole on steroidogenesis: I. Leydig cell enzyme activity in vitro.

The in vitro inhibition of Leydig cell microsomal steroidogenesis by ketoconazole, a potent P-450 dependent enzyme blocker, was evaluated in the human, stallion and pig. Purified Leydig cells were isolated by mechanical dispersion of teased, decapsulated whole testes and sieving through a 0.25 mm stainless steel mesh. The activity of 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta-HSD), 17-hydroxylase (17-OHase), 17,20-desmolase (17,20D), 17-ketosteroid reductase (17-KSR) and aromatase were measured using a constant amount (50 microM) of 14C-labelled substrates in the presence of varying concentrations of pure ketoconazole. Products were isolated by thin layer chromatography and verified by derivative formation. 17-OHase and 17,20D activities were significantly inhibited (p less than .001) by ketoconazole at concentrations as low as 5 microM. 3 beta-HSD, 17-KSR and aromatase activities were only significantly inhibited by ketoconazole at concentrations of 500 and 5000 microM. These data describe the specific loci of inhibition of ketoconazole on testicular steroidogenesis and confirm the observations that ketoconazole is an effective inhibitor of androgen biosynthesis in several species.

The effect of ketoconazole on steroidogenesis. II. Adrenocortical enzyme activity in vitro.

The activity of five adrenocortical steroidogenic enzymes, 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta-HSD), 17-hydroxylase (17-OHase) 17,20 desmolase (17,20D), 21-hydroxylase (21-OHase) and 11-hydroxylase (11-OHase), were measured in vitro in purified mitochondria or microsomes from rhesus monkey (Macaca mulata) and human adrenal tissue in the presence and absence of graded concentrations of ketoconazole. Rhesus 3 beta-HSD activity was unaffected by ketoconazole at concentrations up to 5000 microM. However, human adrenal 3 beta-HSD was inhibited by approximately 40% (p less than .01) at concentrations of 500 microM and by 80% at 100 microM. 17-OHase and 17,20D were significantly inhibited in the human at 5 microM (p less than .001) and in the rhesus monkey at 50 microM (p less than .001). A similar inhibitory effect was found on microsomal 21-OHase, with significant inhibition at 5 microM ketoconazole in the human and rhesus monkey (p less than 0.001). Mitochondrial 11-OHase was also significantly inhibited by ketoconazole in both the human (p less than .005) and rhesus (p less than .001) at 2.0 microM. These results represent documentation of the specific adrenal steroidogenic steps affected by ketoconazole and confirm the observations that this imidazole derivative is a powerful inhibitor of enzymes in the glucocorticoid pathway.

Ketoconazole inhibits multiple steroidogenic enzymes involved in androgen biosynthesis in the human ovary.

Ketoconazole (KZ) has been shown to inhibit testicular and adrenal steroidogenesis and is useful in the medical management of gonadotropin-independent precocious puberty, prostatic cancer, and Cushing's syndrome. To determine whether KZ similarly affects ovarian steroidogenesis, the authors examined its effect on the activity of the human ovarian 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta-HSD), 17-hydroxylase (17-OH), and aromatase (AR) in vitro. A dose-dependent decrease in the activities of 3 beta-HSD and 17-OH was observed with increasing amounts of KZ. With 10, 50, and 100-fold excess KZ, the activity of 3 beta-HSD decreased by 59% (P less than 0.001), 73% (P less than 0.005), and 85% (P less than 0.005), respectively. At equimolar concentrations with substrate (50 microM), KZ inhibited 17-OH by 70% (P less than 0.01). No significant effect on ovarian AR activity was observed, except at the highest concentration of KZ tested. The authors conclude that low concentrations of KZ profoundly inhibit the activity of human ovarian 3 beta-HSD and 17-OH in vitro. These observations suggest that KZ might be useful in the medical management of women with hyperandrogenism, but further experimentation and clinical trials will be necessary.