DNA microarrays in clinical oncology.

Aberrant gene expression is critical for tumor initiation and progression. However, we lack a comprehensive understanding of all genes that are aberrantly expressed in human cancer. Recently, DNA microarrays have been used to obtain global views of human cancer gene expression and to identify genetic markers that might be important for diagnosis and therapy. We review clinical applications of these novel tools, discuss some important recent studies, identify promising avenues of research in this emerging field of study, and discuss the likely impact that expression profiling will have on clinical oncology.     

Right heart pressure determination by Doppler in infants with tricuspid regurgitation

Doppler and direct measurements of right ventricle to right atrial pressure drop were made during cardiac catheterisation on 28 occasions in 26 infants with congenital heart disease. Age was 10 days to 12 months (median 4.5 months), and weight was 3.1 to 9.0 kg (median 4.7 kg). We measured peak velocity of tricuspid regurgitation by continuous wave Doppler, and the pressure drop was calculated using the modified Bernoulli equation (delta p = 4v2). There was a high correlation (r = 0.95) between direct and Doppler measurements. Doppler values tended to underestimate the right ventricle to right atrial pressure drop, but this was not of clinical significance (mean 2 mm Hg). The 95% confidence interval for the Doppler velocity was -0.41 to +0.26 m/sec, and was consistent across the range of pressures studied. Variability between observers was tested, by two observers performing sequential paired examinations on 16 newborn babies with tricuspid regurgitation. The coefficient of repeatability was 6.3 mm Hg (95% confidence interval 4.7 to 9.5 mm Hg) or 0.26 m/sec (0.18 to 0.50 m/sec). This method of right ventricular pressure estimation, validated previously only in older children and adults, is a reproducible and accurate technique in infants with tricuspid regurgitation.     

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.     

Studies of marginal zinc deprivation in rhesus monkeys. V. Fetal and infant skeletal effects

Skeletal maturation was evaluated in newborn and infant rhesus monkeys that had been subjected to a marginally zinc-deficient diet (4 ppm zinc) from conception through 12 months of postnatal life. Serial radiographic assessment of skeletal development was performed and compared to both ad libitum and pair-fed controls. Radiographs were obtained at birth and at 1, 3, 9, and 12 months of age. In each age group a maturation indicator was selected to identify individuals with abnormal skeletal maturation defined on the basis of presence of epiphyseal ossification centers. Animals were compared only within a given sex group. Additionally, to evaluate endochondral bone mineralization, the appearance of the zone of provisional calcification on the metaphyseal side of the growth plate and the width of the growth plate were assessed. A marginal level of zinc deprivation during gestation and during the 1st yr of life was found to be associated with significantly delayed skeletal maturation and defective mineralization. This abnormality of bone mineralization has many features similar to human rachitic syndromes and suggests that zinc plays an important role in endochondral bone formation.     

Failure of ablation of a mediastinal parathyroid adenoma by repeated contrast staining

In a patient with primary hyperparathyroidism an attempt was made to ablate a middle mediastinal parathyroid gland by forceful staining with radiographic contrast material. The gland was stained on two separate occasions, two weeks apart. Both times the serum calcium level temporarily fell to the normal range but reverted to abnormal levels. The patient ultimately required surgery for correction of hypercalcemia. The mechanism of staining and possible reasons for failure as well as potential complications are discussed.     

Immunologic defects in lung cancer patients.

Ninety-three patients with lung cancer were evaluated by delayed cutaneous hypersensitivity testing. Twenty-eight of these patients were evaluated by in vitro lymphocyte function. Thirty-three patients were evaluated prior to surgery and defects in the immune response were closely associated with unresectable disease. In vitro and in vivo studies indicate an antigen recognition defect in the cellular immune mechanisms of these patients. Preliminary studies suggest that the immunopotentiating agent Levamisole may be able to augment this defective cellular immunity in patients with lung cancer.     

In vitro assessment of immunocompetence in patients with malignant melanoma

Ninety-four patients with malignant melanoma and 96 healthy controls were tested for lymphocyte proliferative capacity in a microblastogenesis assay. Each lymphocyte sample was assayed for incorporation of (³H)thymidine after stimulation with PHA, PWM, Con A (two doses), PPD, and allogeneic lymphocytes (MLC). MLC was the only assay that revealed a substantial and significant difference between the melanoma patients and controls. Almost all assays showed lower values in patients with more advanced disease. However, it was not possible to accurately predict clinical outcome from data obtained from in vitro immunocompetence tests. These results indicate the relatively limited clinical usefulness of assays of lymphocyte proliferative capacity in melanoma patients.