Symposium on the diagnosis and treatment of common cancers. 1. Lung cancer--1983

The frequency of lung cancer, common in both men and women, seems to be increasing rapidly, particularly in women. The main causative factor appears to be cigarette smoking. Diagnosis and staging have not changed notably in the last few years, although the advent of computerized tomography and gallium scanning have been of some help in identifying mediastinal tumours, which are unresectable. Further refinements in these techniques may allow us to avoid mediastinoscopy but, at present, this is still usually necessary before operation for lung cancer. Operation is the major form of therapy for non-small cell cancer when this is medically and technically possible. Adjuvant therapy in the treatment of this type of lung cancer has so far been of little help. Radiotherapy as primary treatment, although occasionally curative, should be used only if patients refuse operation or clearly have medical contraindications for thoracotomy. Radiotherapy is very useful for palliation. Chemotherapy is of little value in treating advanced, non-small cell lung cancer, although responses can be seen in up to 40% of patients. This does not translate into important, long-term survival, but responders do survive longer than non-responders. Patients with small cell lung cancer should be treated with combination chemotherapy, with or without thoracic irradiation and with or without cranial irradiation. The latter two modalities have not yet been proved to prolong survival, but may reduce the morbidity. Immunotherapy has not been shown to benefit those with non-small cell lung cancer. Thymosin was beneficial in one controlled trial in patients with small cell lung cancer, but this must be confirmed. In the future, many new approaches will be necessary to control or eradicate this steadily increasing cause of cancer death.     

Soy protein containing isoflavones does not decrease colorectal epithelial cell proliferation in a randomized controlled trial

BACKGROUND: Soy isoflavones have numerous biological properties that suggest that they may protect against colorectal cancer. Colorectal epithelial cell proliferation has been used extensively as an intermediate endpoint biomarker for colorectal neoplasia. OBJECTIVE: We tested the hypothesis that supplementation with soy protein containing isoflavones decreases colorectal epithelial cell proliferation. DESIGN: A 12-mo randomized intervention was conducted in men and women aged 50-80 y with recently diagnosed adenomatous polyps. One hundred fifty participants were enrolled and randomly assigned to an active treatment group (58 g protein powder/d containing 83 mg isoflavones/d; +ISO) or a control group (ethanol-extracted soy-protein powder containing 3 mg isoflavones; -ISO). Biopsy specimens from the cecum, sigmoid colon, and rectum were collected at baseline and at the 12-mo follow-up. Ki-67 antibody immunohistostaining was used to detect cell proliferation. One hundred twenty-five participants completed the study, and proliferation was measured in the first 91 who completed the study. RESULTS: In the sigmoid colon, cell proliferation increased by 0.9 (95% CI: 0.09, 1.9) labeled nuclei per crypt more (11%) in the +ISO group than in the -ISO group over the 12-mo intervention, which was opposite the direction predicted. The number of labeled nuclei per 100 mum crypt height also increased more in the +ISO than in the -ISO group. In the cecum and sigmoid colon, but not in the rectum, the proliferation count increased as the serum genistein concentration increased. Proliferation distribution and crypt height were not changed by treatment at any site. CONCLUSIONS: Supplementation with soy protein containing isoflavones does not reduce colorectal epithelial cell proliferation or the average height of proliferating cells in the cecum, sigmoid colon, and rectum and increases cell proliferation measures in the sigmoid colon.     

Comparison of amikacin and tobramycin in the treatment of infection in patients with cancer.

Two new aminoglycoside antibiotics, tobramycin and amikacin, were compared in a randomized study of the treatment of infections in patients with cancer. For the identified infections, the response rate for tobramycin was 60% and for amikacin was 64%. Pneumonia, urinary tract infection, and septicemia were the most frequent infections. Most (78%) of the identified pathogens were gram-negative bacilli; Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa were the most frequently isolated organisms. When only infections due to gram-negative bacilli were considered, 67% responded to tobramycin and 69% responded to amikacin. All infections except pneumonias had at least a 50% response rate to either antibiotic. The major form of toxicity of both antibiotics was azotemia and occurred in 22% of cases treated with tobramycin and in 20% treated with amikacin. Tobramycin and amikacin are equally effective in the treatment of gram-negative infections and have similar toxicity.     

Malpractice risks associated with colon cancer and inflammatory bowel disease

Analyses of lawsuits against gastroenterologists suggest that the disorders of colon cancer and inflammatory bowel disease are among the more common disorders resulting in malpractice claims, with colon cancer suits receiving some of the highest monetary judgments. Unfortunately, that composite data does not specify the exact alleged wrongdoing, but uses global categories such as "errors of diagnosis." This review will focus on potential legal pitfalls regarding those disorders. The focus is on the legal theories, not the exact medical approach recommended, and is intended as general education, and not legal advice for any specific patient.     

Trimodal spectroscopy for the detection and characterization of cervical precancers in vivo

OBJECTIVE: The objective of this study was to assess the potential of 3 spectroscopic techniques (intrinsic fluorescence, diffuse reflectance, and light scattering) individually and in combination (trimodal spectroscopy) for the detection of cervical squamous intraepithelial lesions. STUDY DESIGN: The study was conducted with 44 patients who underwent colposcopy for the evaluation of an abnormal Papanicolaou smear. Fluorescence and reflectance spectra were collected from colposcopically normal and abnormal sites and analyzed to extract quantitative information about tissue biochemistry and morphologic condition. This information was compared with histopathologic classification, and diagnostic algorithms were developed and validated with the use of logistic regression and cross-validation. RESULTS: Diagnostically significant differences exist in the composition of fluorescing biochemicals, the scattering properties, and the epithelial cell nuclear morphology of cervical squamous intraepithelial lesions and non-squamous intraepithelial lesions. Trimodal spectroscopy is a superior tool for the detection of cervical squamous intraepithelial lesions than any 1 of the techniques alone. CONCLUSION: Trimodal spectroscopy has the potential to improve the in vivo detection of precancerous cervical changes.     

Cimetidine use and gastric cancer

We conducted a case-control study at Group Health Cooperative of Puget Sound to investigate the relation between long-term cimetidine use and gastric cancer. Five of 99 cases of gastric cancer were exposed to cimetidine at least two years before diagnosis, whereas nine of 365 controls (selected from among users of the Group Health Cooperative pharmacy, matched on age, sex, and first year of pharmacy use) were similarly exposed. The odds ratio comparing users with nonusers was 2.3 (95% CI = 0.8-6.9). The odds ratio comparing users of antacids with nonusers was similar, 1.9 (95% CI = 1.0-3.7). Although a causal relation between gastric cancer and cimetidine is possible, the similarity of the findings for cimetidine and antacids lends support to other explanations.     

Enalapril and renal injury in spontaneously hypertensive rats

Rats of the spontaneously hypertensive strain develop kidney damage that resembles the nephropathy seen in some cases of human essential hypertension. Previous studies with a triple drug antihypertensive regimen indicated that proteinuria and glomerular histopathology in spontaneously hypertensive rats might develop despite long-term effective control of systemic blood pressure. To investigate further the relation between hypertension and kidney disease, a group of spontaneously hypertensive rats were treated with enalapril at 15 weeks of age. Blood pressure, protein excretion, and kidney function were measured in those rats at regular intervals during the next year and a half and were compared with untreated spontaneously hypertensive rats and the normotensive Wistar-Kyoto parent strain. Kidney tissue samples from all three groups, collected at autopsy, were stained by immunohistochemical and conventional methods to assess the relative severity and nature of kidney damage. Although enalapril therapy was completely effective in controlling the blood pressure of spontaneously hypertensive rats, it only postponed the onset of kidney disease. Enalapril-treated spontaneously hypertensive rats eventually exhibited albuminuria as severe as that found in hypertensive rats. Kidney vessel pathology was completely prevented with enalapril, but the abnormal accumulation of mononuclear cells in tubulointerstitial and periglomerular sites was the same as in untreated spontaneously hypertensive rats. We have concluded that elevated protein excretion in rats of the spontaneously hypertensive rat strain is not a secondary consequence of systemic hypertension. Structural abnormalities of renal vessels also do not appear to contribute significantly to the pathogenesis of albuminuria in spontaneously hypertensive rats. Other explanations must be sought to account for the close link between spontaneous hypertension and kidney damage in this animal model. The clear dissociation of kidney disease from systemic hypertension exhibited by spontaneously hypertensive rats may also be relevant for human disease.