Squamous cell carcinoma of the oropharynx: Ki-67 and p53 can identify patients at high risk for local recurrence after surgery and postoperative radiotherapy

PURPOSE: To assess the prognostic value of biologic (p53, Ki-67) and clinical factors in squamous cell carcinoma of the oropharynx after radical surgery and postoperative radiotherapy (RT). METHODS AND MATERIALS: Between 1985 and 1995, a total of 102 patients with 104 tumor sites were entered onto the study. Fifty-five primary tumors (53%) involved the tonsils, 26 (25%) the soft palate, and 23 (22%) the base of the tongue. Median age was 53 years (range 36-80 years). The clinical T- and N-categories (UICC 1997) were: T1 (30), T2 (47), T3 (22), T4 (5), N0 (33), N1 (28), N2 (42), and N3 (1). Histologically-clear margins were achieved in all patients by initial surgery. Postoperative RT to the primary and regional lymphatics was given, to a total of 60 Gy in 6 weeks, and single daily fractions of 2 Gy. The expression of the nuclear p53- and Ki-67-labeling index (LI) was investigated by immunostaining using the monoclonal antibodies DO-7 and MIB 1. The nuclear p53-intensity (p53-I) was graded into 4 categories (0/+/++/) by densitometry. Median follow-up was 43 months (range 14-132 months). RESULTS: Cancer-specific survival, disease-free survival, and locoregional tumor control rates were 74%, 69%, and 75%, respectively, at 5 years. Significant prognostic factors for disease-free survival were: T-category (T1/2: 77% vs. T3/4: 53%, p = 0.02), tumor site (tonsils: 79% vs. soft palate: 70% vs. base of tongue: 45%, p = 0.05), duration of RT (< or = 46 days: 80% vs. > 46 days: 60%, p = 0.04), Ki-67 LI (< or = 20%: 84% vs. > 20%: 49%, p = 0.006) and p53-I (0/+: 56% vs. ++/ : 79%, p = 0.008). A significant prognostic impact on locoregional control was noted for the duration of RT (< or = 46 days: 86% vs. > 46 days: 68%, p = 0.01), tumor site (tonsils: 88% vs. soft palate: 67% vs. base of tongue: 51%, p = 0.02), Ki-67 LI (< or = 20% LI: 87% vs. > 20% LI: 56%, p = 0.018), and the p53-I (0/+: 58% vs. ++/ : 88%, p = 0.0006). On multivariate analysis, the p53 nuclear intensity (p = 0.002) and the Ki-67 index (p = 0.01) remained the only significant factors for locoregional control. CONCLUSION: Ki-67 labeling index above 20% and a weak p53 nuclear intensity (0/+) are both able to identify patients with squamous cell carcinoma of the oropharynx being at high risk for local recurrence after surgery and postoperative RT. Consequently, in this subgroup an intensification of treatment may be contemplated in prospective trials.     

New developments in the use of peptide gonadotropin-releasing hormone antagonists versus agonists

Gonadotropin-releasing hormone (GnRH) stimulates the pituitary secretion of both luteinising hormone (LH) and follicle-stimulating hormone (FSH), and thus controls the hormonal and reproductive functions of the gonads. The blockade of the effects of GnRH may be sought for a variety of reasons; for example, to control premature LH surges and to reduce the cancellation rate with the aim of improving the pregnancy rate per treatment cycle or in the treatment of sex hormone-dependent disorders. Selective blockade of LH/FSH secretion and subsequent chemical castration have previously been achieved by desensitising the pituitary to continuously administered GnRH or by giving long-acting GnRH agonists. GnRH analogues are indicated for clinical situations in which the suppression of endogenous gonadotropins (precocious puberty, contraception and controlled ovarian hyperstimulation) or sexual steroids (endometriosis, prostate hyperplasia, cancer and uterine fibroids) is desired. The immediate suppression of the pituitary that is achieved by GnRH antagonists without an initial stimulatory effect is the main advantage of these compounds over the agonists. GnRH antagonists have been developed for clinical use with acceptable pharmacokinetic, safety and commercial profiles. In assisted reproduction, these compounds seem to be as effective as established therapy, but with shorter treatment times, less use of gonadotropic hormones, improved patient acceptance, and fewer follicles and oocytes. All of the current indications for GnRH agonist desensitisation may prove to be indications for a GnRH antagonist, including endometriosis, leiomyoma and breast cancer in women, benign prostatic hypertrophy and prostatic carcinoma in men, and central precocious puberty in children. However, the best clinical evidence has been in assisted reproduction and prostate cancer.     

Screening housing to prevent lead toxicity in children

OBJECTIVE: Screening children to identify those with blood lead levels > or = 10 microg/dl fails to protect children from lead-associated cognitive deficits and behavioral problems. To broaden our efforts at primary prevention, screening criteria are needed to identify lead-contaminated housing before children are unduly exposed. The purpose of this study was to identify and validate housing characteristics associated with children having elevated blood lead levels (> or = 10 microg/dl). METHODS: Two existing studies were used to examine housing characteristics linked with undue lead exposure: a cross-sectional study of 205 children aged 12 to 31 months, and a random sample from a longitudinal study of 276 children followed from 6 to 24 months of age. Logistic regression analysis was conducted to examine the association of children's blood lead levels > or = 10 microg/dl. RESULTS: The mean age of the 481 children was 17.8 months; 99 (20.6%) had a blood lead concentration of 10 microg/dl or higher. The following characteristics were associated with blood lead concentration > or = 10 microg/dl: floor lead loading > 15 microg/ft2 (odds ratio [OR]=2.2; 95% confidence interval [CI] 1.3, 3.8); rental housing (OR=3.2; 95% CI 1.3, 7.6); poor housing condition (OR=2.1; CI 1.2, 3.6); African American race (OR=3.3; CI 1.9, 6.1); paint chip ingestion (OR=5.8; CI 1.3, 26.5); and soil ingestion (OR=2.2; CI 1.1, 4.2). Housing characteristics including rental status, lead-contaminated floor dust, and housing condition had a range of sensitivity from 47% to 92%; specificity from 28% to 76%; a positive predictive value from 25% to 34%; and a negative predictive value of 85% to 93%. CONCLUSIONS: Housing characteristics and floor dust lead levels can be used to screen housing to identify lead hazards prior to occupancy, before purchasing a home, or after renovation to prevent children's exposure to lead hazards.     

Ambulatory treatment of anal fissure

Not a long time ago, the standard treatment for anal fissure was surgical, inpatient care; this concept failed in the last years, ambulatory treatment becoming the rule and the inpatient care the exception. We wish to present here our results in 125 ambulatory patients, who were referred to our proctologic office with anal fissure. We used two methods: a conservative one, by applying topical 0.2% nitroglycerine, similar to other proctology practitioners, and one method of our own which is a minimal surgical procedure consisting of sphincterotomy. The average follow-up period was 6 months. Symptom-free and anatomic-free states were obtained in 61.2% for conservative treated patients and in 91.4% for operated patients, respectively. We had no postoperative complications, rebounds or sequelae. We consider the results at least equal in effectiveness to those of standard surgical treatment. This is why we underline that ambulatory treatment for anal fissure reaches the goal to be of a first line option.     

Comparison of relative binding affinities of endocrine active compounds to fathead minnow and rainbow trout estrogen receptors

Twelve chemicals were tested for binding affinity to rainbow trout liver estrogen receptor (rbtER) and fathead minnow liver ER (fhmER). The chemicals included estradiol (E2), diethylstilbestrol (DES), ethinylestradiol (EE2), estrone (El), estriol, tamoxifen (TAM), genistein (GEN), p-nonylphenol (PNP), p-tert-octylphenol (PTOP), methoxychlor (MXC), testosterone, and methyltestosterone (MT). Relative binding affinity (RBA) was calculated for each chemical as a function of E2 binding to the receptor. The estrogens DES, EE2, and E1 bound with high affinity to both receptors, with respective RBAs of 583, 166, and 28% (fathead minnow) and 179, 89, and 5% (rainbow trout). Relative binding affinity of E3, TAM, and GEN for both fhmER and rbtER were moderate, with values between 0.3 and 5%. The alkylphenols had weak affinity for the ERs with RBAs for the fhmER of 0.1 and 0.01 for PNP and PTOP, respectively. Corresponding values for the rbtER are 0.027 and 0.009. Estradiol ([3H]E2) only partially was displaced from both the fhmER and the rbtER by MXC, T, and MT. Comparison of RBAs of the chemicals tested for fhmER and rbtER indicates that the rank order of RBAs essentially are the same for both species.     

Hemangiomas of infancy: treatment of ulceration in the head and neck

Ulceration is a common complication of hemangiomas of infancy and presents a therapeutic dilemma for the head and neck-facial plastic surgeon. Multiple therapies are available, further complicating treatment of patients. We review the common characteristics of ulcerated hemangiomas and discuss the treatment modalities available. We present case reports to illustrate management options and a stepwise algorithm for treatment of ulcerated hemangiomas.     

Effect of a clinical trial alert system on physician participation in trial recruitment

BACKGROUND: Failure to recruit a sufficient number of eligible subjects in a timely manner represents a major impediment to the success of clinical trials. Physician participation is vital to trial recruitment but is often limited. METHODS: After 12 months of traditional recruitment to a clinical trial, we activated our electronic health record (EHR)-based clinical trial alert (CTA) system in selected outpatient clinics of a large, US academic health care system. When a patient's EHR data met selected trial criteria during the subsequent 4-month intervention period, the CTA prompted physician consideration of the patient's eligibility and facilitated secure messaging to the trial's coordinator. Subjects were the 114 physicians practicing at selected EHR-equipped clinics throughout our study. We compared differences in the number of physicians participating in recruitment and their recruitment rates before and after CTA activation. RESULTS: The CTA intervention was associated with significant increases in the number of physicians generating referrals (5 before and 42 after; P < .001) and enrollments (5 before and 11 after; P = .03), a 10-fold increase in those physicians' referral rate (5.7/mo before and 59.5/mo after; rate ratio, 10.44; 95% confidence interval, 7.98-13.68; P<.001), and a doubling of their enrollment rate (2.9/mo before and 6.0/mo after; rate ratio, 2.06; 95% confidence interval, 1.22-3.46; P = .007). CONCLUSIONS: Use of an EHR-based CTA led to significant increases in physicians' participation in and recruitment rates to an ongoing clinical trial. Given the trend toward the EHR implementation in health care centers engaged in clinical research, this approach may represent a much-needed solution to the common problem of inadequate trial recruitment.