Carcinoma of the skin of the head and neck with perineural invasion.

BACKGROUND: Perineural invasion is observed in a small subset of patients with carcinomas of the skin of the head and neck. METHODS: Review of the patient literature highlighting the University of Florida experience. RESULTS: Patients with early perineural invasion are asymptomatic, and the phenomenon is discovered only on pathologic examination of the excised lesion. These patients are defined as having "incidental" perineural invasion, and treatment with surgery followed by postoperative irradiation results in a cure rate of approximately 80%. Undiagnosed, the perineural carcinoma slowly progresses and eventually results in symptoms, usually facial weakness or numbness. The disease eventually extends to the skull base and becomes incompletely resectable. Symptomatic patients are defined as having "clinical" perineural invasion, and aggressive treatment results in a cure rate of approximately 45%. CONCLUSIONS: Perineural invasion is an uncommon spread pattern observed in patients with skin cancer and is associated with a relatively poor prognosis. The likelihood of cure is inversely related to the proximal extent of the cancer and is lower for symptomatic compared with asymptomatic patients.     

Postcricoid region and cervical esophagus: normal appearance at CT and MR imaging

PURPOSE: To establish the normal variations of the postcricoid portion of the hypopharynx, esophageal verge, and cervical esophagus, as seen on computed tomographic (CT) and magnetic resonance (MR) images. MATERIALS AND METHODS: One hundred twenty-one CT and 92 MR images were reviewed. Diameter and wall thickness were measured at multiple levels. Depiction of the layers of the musculature and adjacent fat planes was evaluated. The frequency and size of the tracheoesophageal lymph nodes were noted. RESULTS: An esophageal anteroposterior diameter greater than 16 mm and lateral diameter greater than 24 mm were considered abnormal. The average wall thickness was 4.8 mm laterally and 3.8 mm posteriorly. Demonstration of the intramural fat planes of the postcricoid region decreased from the upper to the lower region of the cricoid cartilage. The ability to separate the esophageal wall from the trachea was highest at the esophageal verge and declined markedly more distally. The tracheo-esophageal groove nodes were seen more often on the right (mean size [+/- SD], 4.5 mm +/- 2.2). CONCLUSION: Knowledge of the normal appearance and variations of the post-cricoid region and cervical esophagus is essential in detecting abnormalities in these areas.     

Down-regulation of insulin-like growth factor I receptor activity by NVP-AEW541 has an antitumor effect on neuroblastoma cells in vitro and in vivo.

PURPOSE: Signaling through insulin-like growth factor I receptor (IGF-IR) is important for growth and survival of many tumor types. Neuroblastoma is sensitive to IGF. EXPERIMENTAL DESIGN: We assessed the ability of NVP-AEW541, a recently developed small molecule that selectively inhibits IGF-IR activity, for neuroblastoma growth effects in vitro and in vivo. Our data showed that, in a panel of 10 neuroblastoma cell lines positive for IGF-IR expression, NVP-AEW541 inhibited in vitro proliferation in a submicromolar/micromolar (0.4-6.8) range of concentrations. RESULTS: As expected, NVP-AEW541 inhibited IGF-II-mediated stimulation of IGF-IR and Akt. In addition to growth inhibition, the drug also induced apoptosis in vitro. Oral administration of NVP-AEW541 (50 mg/kg twice daily) inhibited tumor growth of neuroblastoma xenografts in nude mice. Analysis of tumors from the drug-treated animals revealed a marked apoptotic pattern and a decrease in microvascularization compared with controls. Interestingly, quantitative real-time PCR detected both in vitro and in vivo a significant down-regulation of mRNA for vascular endothelial growth factor (VEGF) caused by NVP-AEW541. In addition, in Matrigel-coated chambers and in severe combined immunodeficient mice tail vein injected with neuroblastoma cells, tumor invasiveness was significantly reduced by this agent. Analysis of IGF-IR expression in a series of 43 neuroblastoma primary tumors revealed IGF-IR positivity in 86% of cases. CONCLUSIONS: Taken together, these data indicate that NVP-AEW541 can be considered as a novel promising candidate for treatment of neuroblastoma patients.     

Correlation between anemia and functional/cognitive capacity in elderly lung cancer patients treated with chemotherapy.

BACKGROUND: Elderly cancer patients are often excluded from clinical trials and no data are available on the impact of chemotherapy-related anemia on their functional status and cognitive functions. This observational study investigates the association between hemoglobin (Hb) level and comprehensive geriatric assessment (CGA) variables (MMSE, ADL/IADL, GDS, CIRS and VAS). PATIENTS AND METHODS: We enrolled 42 consecutive lung cancer elderly patients undergoing chemotherapy that were evaluated at baseline and after each CT cycle at least until cycle 2. Hb association with CGA indexes was expressed using Spearman's non-parametric coefficient r. RESULTS: Higher Hb values were significantly associated with more favourable values of all indexes measuring mental and functional capacity, depression and comorbidities. For all indexes except IADL, improvements from baseline were significantly related with concomitant Hb increases. In 14 patients given erythropoietin during the first two cycles, mean Hb increased from 9.2 to 10.8 g/dl, and the mean values of all CGA indexes were improved. On the contrary, in 18 patients not given erythropoietin, Hb varied from 13.0 to 11.2 g/dl and a parallel worsening in all CGA indexes was observed. CONCLUSIONS: Chemotherapy-related anemia is associated with impairment of functional status and cognitive functions. In elderly cancer patients anemia correction or maintenance could be useful to preserve functional independency and protect from mental decay. However, the study results need to be confirmed on a larger series of patients within a controlled clinical trial.     

The impact of primary tumor volume on local control for oropharyngeal squamous cell carcinoma treated with radiotherapy

BACKGROUND: A study was needed to determine the effect of primary tumor volume on local control of oropharyngeal carcinoma treated with radiation therapy, with or without induction chemotherapy. METHODS: Between July 1983 and April 1995, 114 patients with T2-T4 squamous cell carcinoma of the oropharynx were treated for cure with radiation therapy, with or without induction chemotherapy, and had a pretreatment CT scan available for retrospective review. All scans were reviewed by a single radiologist (A. A. M.) to determine the tumor volume of the primary lesion. Volume was measured with a computer digitizer for each CT slice showing the primary lesion. RESULTS: A large variation in tumor volume within a given T stage was found. Multivariate analysis demonstrated T stage to be the most significant factor affecting local control. Tumor volume marginally influenced local control (p =.10). CONCLUSIONS: Primary tumor volume varies significantly within a given T stage and has a marginal impact on the likelihood of local control after radiotherapy.     

T1rho imaging of murine brain tumors at 4 T

RATIONALE AND OBJECTIVES: The goal of this study was to evaluate the utility of T1rho weighting in magnetic resonance imaging of murine brain tumors. MATERIALS AND METHODS: S91 Cloudman melanoma was implanted in mouse brains (n = 4). A T2-weighted spin-echo (SE) and a T1rho-weighted fast SE-based sequence were performed on a 4-T clinical imager. T2 and T1rho maps were computed. The tumor-to-normal-tissue contrast was compared between T2-weighted, T1rho-weighted, proton-density-weighted, and pre- and postcontrast T1-weighted SE images. RESULTS: The tumor-tissue contrast of the T1rho-weighted images was similar to that of the T2-weighted images but less than that of the postcontrast T1-weighted images. The T1rho-weighted images provided better definition of tumor boundaries than T2-weighted images. At spin-locking powers of 0.5 and 1.5 kHz, the T1rho of the tumor was 64.0 msec +/- 0.46 and 68.65 msec +/- 0.59, respectively. There was no significant inter- or intra-animal variation in T1rho for tumor or normal brain cortex. CONCLUSION: T1rho-weighted imaging performed at low spin-lock strengths qualitatively depicted tumor borders better than proton-density or T2-weighted imaging and could be useful in treatment planning when combined with other imaging sequences.     

Patients' expectations of knee surgery.

BACKGROUND: Patients' expectations of medical care are linked to their requests for treatment and to their assessments of outcome and satisfaction. Our goals were to measure patients" preoperative expectations of knee surgery and to develop and test patient-derived knee expectations surveys. METHODS: An initial sample of 377 patients (mean age, 54.6 18.2 years; 52% women) was enrolled in the survey-development phase. One hundred and sixty-one (43%) of these patients subsequently underwent total knee arthroplasty; seventy-five (20%), cruciate ligament repair; eighty-five (23%), meniscal surgery; and fifty-six (15%), surgery for another knee condition. Preoperatively, these patients were asked open-ended questions about their expectations of knee surgery. Their responses were grouped with use of qualitative research techniques to generate categories of expectations. Categories were transformed into specific questions and were formatted into two draft surveys, one for patients undergoing total knee arthroplasty and one for patients undergoing other surgical procedures on the knee. A second sample of 163 patients (mean age, 55.1 17.5 years; 49% women) was enrolled in the survey-testing phase, and they completed the draft surveys on two separate occasions to establish test-retest reliability. Items were selected for the final surveys if they were cited by 5% of the patients, if they represented important functional changes resulting from surgery, or if they represented potentially unrealistic expectations. All selected items fulfilled reliability criteria, defined as a kappa (or weighted kappa) value of 0.4, or were deemed to be clinically relevant by a panel of orthopaedic surgeons. RESULTS: From the survey-development phase, a total of fifty-two categories of expectations were discerned; they included both anticipated items such as pain relief and improvement in walking ability and unanticipated items such as improving psychological well-being. Expectations varied by diagnosis and patient characteristics, including functional status. Two final surveys were generated: the seventeen-item Hospital for Special Surgery Knee Replacement Expectations Survey and the twenty-item Hospital for Special Surgery Knee Surgery Expectations Survey. Each required less than five minutes to complete. CONCLUSIONS: Patients have multiple expectations of knee surgery in the areas of symptom relief and improvement of physical and psychosocial function, and these expectations vary according to the diagnosis. We developed two valid and reliable surveys that can be used preoperatively to direct patient education and shared decision-making and to provide a framework for setting reasonable goals. Reexamining patients' responses postoperatively could provide a way to assess fulfillment of expectations, which is a crucial patient-derived measure of outcome and satisfaction.     

Expression of HER-2/neu oncoprotein, DNA-ploidy and S-phase fraction in advanced ovarian cancer

The immunohistochemical expression of HER-2/neu and cytofluorimetric data were retrospectively analyzed in a group of primary advanced ovarian cancers. Thirty-three out of 94 (35%) cases showed a specific p185/neu immunoreaction. No correlation between p185/neu expression and any of the clinico-pathologic parameters examined was observed. As far as cytofluorimetric data are concerned, 38 out of 69 (55%) of the tumors were diploid (DNA index = 1) while 31 (45%) were aneuploid (DNA index from 1.10 to 2.50 with a median value of 1.50). Ovarian tumors were defined as of low and high S-phase fraction in 68% and 32% of the cases, respectively. Tumor ploidy and S-phase fraction did not correlate with the clinico-pathologic characteristics or p185/neu oncoprotein expression. Aneuploid tumors had a higher S-phase fraction (mean: 15.81 ± 13.44) than diploid tumors (mean: 8.89 ± 7.98) ( P < 0.01). p185/neu expression failed to affect significantly both overall and progression free survival. On the other hand tumor ploidy was found to be related to the prognosis of advanced ovarian cancer patients although the difference was not statistically significant. As far as progression free survival is concerned, the median time to recurrence was not reached for diploid cases whereas it was 21 months for aneuploid cases ( P < 0.05). The 5-year survival for patients with a low S-phase fraction (58%) was significantly higher than for patients with high S-phase fraction tumors (28%) ( P < 0.01). Median time to recurrence was 48 and 17 months for low and high S-phase fraction tumor patients, respectively ( P < 0.05). However, in a multivariate analysis both tumor ploidy and S-phase fraction did not retain their prognostic value. The assessment of the role of the parameters examined in improving the prognostic characterization of ovarian cancer patients should be investigated in large multicenter clinical trials.     

Idarubicinol myelotoxicity: a comparison of in vitro data with clinical outcome in patients treated with high-dose idarubicin

We evaluated in vitro the toxicity of idarubicin and its active metabolite idarubicinol on haematopoietic progenitors, using human umbilical cord blood and peripheral blood progenitors to obtain dose-response curves. We treated 16 patients with poor prognosis lymphoma in a phase I-II trial of high-dose idarubicin and melphalan and investigated if idarubicinol persisting in patients' plasma at the time of transplantation (day 0), on day +1 and +2 could result in an inhibition of infused progenitors. Colony inhibition was correlated with pharmacokinetic data and with the time of patients' engraftment. Plasma samples obtained before idarubicin treatment demonstrated a colony-stimulating effect, increasing the cloning efficiency by 72%. The inhibitory activity on colony forming unit granulocyte-macrophage (CFU-GM) of patients' plasma collected on the day of transplantation was lower than expected from dose-response curves (21% measured vs 70% expected). The time to patients' WBC and PLT recovery correlated with the amount of CD34+ cells reinfused and, to a lesser extent, with the colony-inhibiting effect of patients' plasma. The correlation between idarubicinol concentration and CFU-GM inhibition was not significant. These data suggest that plasma drug concentration on the day of stem cell reinfusion may overestimate the toxicity of residual anthracyclines to the transplanted cells.