Metabolic response to radiation therapy in patients with cancer

The effect of radiation therapy on substrate metabolism was evaluated in five patients with head and neck or lung cancer. Stable isotope tracer methodology was used to determine urea, amino acid, glucose, and lipid kinetics during postabsorptive conditions before initiation, near the midpoint (after receiving 2,672 +/- 36 rads), and at completion (after receiving 6,072 +/- 307 rad) of a 6- to 8-week course of radiation therapy. Nutritional status was maintained throughout the treatment period by providing supplemental enteral feedings as needed. Postabsorptive plasma insulin, catecholamine, and amino acid concentrations did not change during the course of treatment. Before radiation therapy was initiated, values for the plasma rate of appearance (Ra) of urea (3.35 +/- 0.33 micromol x kg(-1) x min(-1)), alpha-ketoisocaproate ([alpha-KIC] 2.16 +/- 0.19 micromol x kg(-1) x min(-1)), phenylalanine (0.59 +/- 0.052 micromol x kg(-1) x min(-1)), and glucose (10.56 +/- 1.31 micromol x kg(-1) x min(-1)) were in the normal range. However, glycerol and palmitate Ra values (3.11 +/- 0.30 and 2.01 +/- 0.33 micromol x kg(-1) x min(-1), respectively) were 25% higher than values observed previously in normal subjects. Substrate flux did not change during radiation therapy, and measurements obtained during the midpoint and at completion of treatment were similar to initial values. These results demonstrate that large doses of radiation therapy, administered over 6 to 8 weeks to the upper body, do not cause significant metabolic stress.     

Fibronectin in tissues and saliva of patients with oral lichen planus

BACKGROUND: Whilst gastrin has been found to be trophic for some colorectal cancer cell lines, and gastrin receptor antagonists are able to block this phenomenon, their potency has been modest. METHODS: The effect of a new, potent and selective CCK B receptor antagonist, CI-988 on the growth of LoVo, a human colon cancer cell line both in vitro and in vivo was instigated. RESULTS: Basal growth of LoVo in vitro was inhibited by up to 58.93 +/- 7.30% with concentrations of CI-988 as low as 1 X 10(-11) mol/L whereas the addition of gastrin (G17) at 0.5 nmol/L had no effect. LoVo was also grown in vivo for 10 days in nude mice subsequently treated with CI-988 at 10 mg/kg per day orally for 20 days. CI-988 inhibited the growth of xenografts by 53%. CONCLUSION: This was the first study in cancer with this potent gastrin receptor antagonist, CI-988. The results suggest that CI-988 may be of use in inhibiting the growth of colorectal cancer.     

Prevalence of mood disorders and utility of the PRIME-MD in patients undergoing radiation therapy

PURPOSE: To validate a short, structured interview procedure that allows practicing oncologists to quickly and reliably identify mood disorders in their patients, and to estimate the prevalence and types of mood disorders in a radiation therapy patient setting, noting relationships between mood disorders and patient characteristics. METHODS: Consecutive, eligible adult patients from the practices of two radiation oncologists were administered the Primary Care Evaluation of Mental Disorders (PRIME-MD) by the treating physician. A subset of these patients was also evaluated with the SCID, administered by trained mental health care personnel. Agreement between the two instruments was examined using the kappa statistic. Prevalence of mood disorders was determined from the PRIME-MD. The significance of relationships between patient characteristics and mood disorders was examined by chi-square and ANOVA analysis, and subsequently by multivariate logistic regression analysis. RESULTS: One hundred twenty-two patients were studied. Fifty-three of these were administered the SCID. Agreement between the two instruments was very good (kappa = 0.70). A diagnosis of a depressive or anxiety disorder by the PRIME-MD was made in 59 of the 122 patients (48%, 95% confidence interval = 39%, 58%). Multivariate analysis showed that a diagnosis of a depressive mood disorder was significantly related to pain intensity and prior history of depression. CONCLUSION: We have demonstrated the validity and feasibility of the PRIME-MD administered by oncologists in making diagnoses of mood disorders. The prevalence of mood disorders in our set of patients undergoing a course of RT was nearly 50%. Future studies should describe the natural history of these disorders, and determine optimal intervention strategies.     

Cardiac effects of adjuvant doxorubicin and radiation therapy in breast cancer patients

PURPOSE: To assess the cardiac effects of two different cumulative doses of adjuvant doxorubicin and radiation therapy (RT) in breast cancer patients. PATIENTS AND METHODS: Two hundred ninety-nine breast cancer patients were prospectively randomized to receive either five cycles (CA5) or 10 cycles (CA10) of adjuvant treatment with cyclophosphamide (500 mg/ m2) and doxorubicin (45 mg/m2) administered by intravenous bolus every 21 days. One hundred twenty-two of these patients also received RT. Estimates of the cardiac RT dose-volume were retrospectively categorized as low, moderate, or high. The risk of major cardiac events (congestive heart failure, acute myocardial infarction) was assessable in 276 patients (92%), with a median follow-up time of 6.0 years (range, 0.5 to 19.4). RESULTS: The estimated risk (95% confidence interval) of cardiac events per 100 patient-years was significantly higher for CA10 than for CA5 [1.7 (1.0 to 2.8) v 0.5 (0.1 to 1.2); P=.02]. The risk of cardiac events in CA5 patients, irrespective of the cardiac RT dose-volume, did not differ significantly from rates of cardiac events predicted for the general female population by the Framingham Heart Study. In CA10 patients, the incidence of cardiac events was significantly increased (relative risk ratio, 3.6; P < .00003) compared with the Framingham population, particularly in groups that also received moderate and high dose-volume cardiac RT. CONCLUSION: Conventional-dose adjuvant doxorubicin as delivered in the CA5 regimen by itself, or in combination with locoregional RT, was not associated with a significant increase in the risk of cardiac events. Higher doses of adjuvant doxorubicin (CA10) were associated with a threefold to fourfold increased risk of cardiac events. This appears to be especially true in patients treated with higher dose-volumes of cardiac RT. Larger studies with longer follow-up periods are needed to confirm these results.     

Propranolol therapy in patients undergoing myocardial revascularization

The records of 185 consecutive patients having myocardial revascularization were reviewed with regard to preoperative administration of propranolol and intraoperative or postoperative complications. Tachycardia and hypertension before cardiopulmonary bypass were slightly more common in patients never taking propranolol or those who had discontinued it for more than 48 hours before operation. There was no statistically significant difference in the incidence of postbypass hypotension among patients who took propranolol within 24 hours of operation, those who discontinued it more than 24 hours before operation, and those who never took the drug. Operative mortality was not significantly different among patients who received propranolol within 48 hours of operation (3%), those who never took it and those who discontinued it more than 48 hours before operation (4%). Early in the series, five patients had an acute myocardial infarction within 48 hours after routine preoperative withdrawal of propranolol. Because complete withdrawal of propranolol in patients with unstable angina pectoris may lead to acute myocardial infarction, we recommend gradual withdrawal of the drug during 48 hours before operation. If this is not possible because anginal pain recurs or intensifies, then reduced doses may be given safely up to 10 hours before revascularization, provided that the patient is a satisfactory candidate for bypass and that adequate myocardial revascularization can be accomplished.     

Iron therapy in patients undergoing maintenance hemodialysis

Studies were conducted of the effect of temperature and humidity, variant of plague microbe, frequency and duration of feeding and specificity of the host on the blockformation in the souslik fleas C. tesquorum and N. setosa infected with plague. 28 tests on the effect of temperature and humidity on the blockformation were undertaken, for which 14411 fleas of the above species were used. A temperature of 16 to 22 degrees proved to be optimal; at this temperature the number of blocked fleas (C. tesquorum) varied from 21.2 to 42.7% and that of N. setosa--from 41.9 to 54.2%. Marmot variant of plague microbe caused the formation of the "block" in 53.3 to 55.1% of fleas of N. setosa in 3-4 days and in 28.0 to 42.7% of C. tesquorum in 10-14 days after the infection. In C. tesquorum the process of blockformation is affected by the frequency of feeding, in N. setosa--by the duration of each feeding.     

Complicating mucosal reactions in patients receiving radiation therapy for head and neck cancer

Radiation mucositis is characterized by erythema, pseudomembranes, and ulceration of mucosa in the irradiated field. We present two cases of oral mucosal changes in patients treated with radiotherapy in the head and neck region, which included mucosal erythema and ulceration outside of the radiated fields. One case was confirmed as herpes virus infection, and the other was diagnosed as Sweet's syndrome. When mucositis extends beyond the radiation fields, the clinician should consider other causes of mucosal inflammation and erythema in order to begin appropriate management.     

Lung cancer after radiation therapy for breast cancer

BACKGROUND: Radiation, including radiation therapy (RT) for a variety of conditions, is known to be a lung carcinogen. METHODS: Data from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute for 1973-1986 were utilized to investigate whether RT for breast cancer affects the risk of subsequent lung cancer. The relative risk was calculated by comparing the incidence rate in patients with irradiated breast cancer with that in those with nonirradiated breast cancer. RESULTS: It was found that the risk of lung cancer overall was increased in women who underwent irradiation compared with those who were not irradiated 10 years after the initial breast cancer diagnosis with a relative risk of 2.0 (95% confidence interval, 1.0-4.3). In addition, the risk of lung cancer was in the ipsilateral lung compared with the contralateral lung for irradiated women. This increase was observed after 10 years for lung cancer overall and for the three major histologic subgroups (small cell, squamous cell, and adenocarcinoma). Specific information on RT doses and treatment plans and cigarette smoking were not available. CONCLUSIONS: It was concluded that RT for breast cancer may increase the risk of lung cancer after a latency period of 10 years.     

Care of patients undergoing immunoglobulin therapy

Immunoglobulin infusion is becoming more widely used as treatment for a variety of conditions. This article describes the background and uses of immunoglobulin therapy and the nursing care of patients undergoing this treatment.     

Organ preservation and quality of life: the quality of life of patients undergoing radiation therapy

In the definition of quality of life (QL) conventional medical indicators (rate of cure, disease-free survival, side-effects, costs) should be combined with those of the patient's personality the impact of the disease, the level of satisfaction, the general health conditions. This assessment being complex, obviously needs an integration of competences for correct decision making in diagnosis and treatment. In oncology, numerous attempts have been made towards the systematization of toxicity in radiotherapy based on physical and functional rather than multidimensional criteria. However the categorization of possible side-effects according to scoring systems already marks an improvement towards the quality assurance of care and thus the patient's quality of life.     

Food avoidance in patients undergoing cancer chemotherapy

The incidence rates of Duchenne and Becker muscular dystrophies (X-linked recessive) in a given sample of the Italian population were recalculated using the results of DNA and dystrophin analysis. While the incidence rate of Duchenne muscular dystrophy remained unchanged, the new figure for the incidence of Becker muscular dystrophy (7.2 per 100,000 male live births) was much higher than previously reported, since molecular diagnosis revealed additional cryptic cases, but this incidence is still an underestimate.     

K-ras gene mutations in normal colorectal tissues from K-ras mutation-positive colorectal cancer patients

K-ras gene mutations have been reported as early events in colorectal tumorigenesis, but their role in tumor initiation and development is still unclear. To analyze and compare K-ras mutational patterns between colorectal tissues at different stages of tumor progression in individual patients, 65 colorectal tissue samples, including carcinoma, adenoma, histologically normal mucosa, submucosal muscularis propria, and histologically normal mucosa distant from tumor, were obtained from 13 patients with colorectal cancer. In addition, normal mucosal tissues obtained from four normal individuals were analyzed. Each of the 13 tumors was shown previously to harbor a mutation in either codon 12 or 13 of the K-ras gene by direct sequencing. These tissues were reanalyzed, using the recently established mutant allele enrichment + denaturing gradient gel electrophoresis method, which can detect one mutant allele in 10(4)-10(5) normal alleles, thus allowing for the analysis of infrequent cells bearing mutations against the background of wild-type cells. No K-ras codon 12 mutation was detected by this method in the histologically normal mucosal tissues sampled at the margin of resection distant from the tumor or in those obtained from four normal individuals. On the other hand, these mutations were detected in 9 of 10 adenoma and 6 of 10 mucosa samples from 10 patients with known K-ras codon 12 mutations, and also in 2 of 3 carcinoma, 2 of 3 adenoma, and 1 of 3 mucosa samples obtained from 3 patients with known K-ras codon 13 mutations. Thus, K-ras codon 12 mutations were found to occur with a high frequency (53.8%) in histologically normal mucosa adjacent to tumors of patients with K-ras mutation-positive colorectal cancer, suggesting that they may be useful biomarkers for early detection of colorectal cancer. Furthermore, multiple K-ras mutations were found in tissues of nearly half of the 13 patients, indicating that distinct evolutionary subclones may be involved in the development of tumor in some patients with colorectal cancer.     

Internal radiation therapy for patients with primary or metastatic hepatic cancer: a review

BACKGROUND: The limited efficacy of current approaches to the treatment of patients with hepatic cancer, including external beam radiation therapy and cytotoxic chemotherapy, has reawakened interest in the use of internal radiation therapy. METHODS: The authors reviewed series of patients with liver metastases or hepatocellular carcinoma (HCC) treated with 1) interstitial irradiation and direct intratumoral injection of 90Y microspheres, 2) intraarterial infusion of (131)I-Lipiodol, 3) intraarterial infusion of 90Y microspheres, or 4) parenteral administration of radiolabeled monoclonal antibodies. RESULTS: High dose rate interstitial irradiation with afterloading of (192)Ir resulted in local control of hepatic metastases for a median of 8 months and complete tumor eradication in 2 patients. Direct intratumoral injection of 90Y microspheres reduced the size of 90.6% of tumors and completely destroyed them in 8 patients. Treatment with arterial (131)I-Lipiodol resulted in a 17-92% response rate as well as a case of complete remission of unresectable HCC. It was found to be most effective against small tumors. No response was observed with liver metastases from colorectal carcinoma. Partial response was commonly achieved when patients with unresectable liver metastases or HCC were treated with intraarterial 9OY microspheres. Among four patients whose HCC became resectable following treatment with 90Y microspheres, two cases of complete remission were documented. In a prospective randomized trial, (131)I-antiferritin combined with chemotherapy was no more effective than chemotherapy alone. CONCLUSIONS: The different approaches to internal radiation therapy that are reviewed in this article represent several ways in which radiation can be selectively targeted to hepatic tumors without undue radiation to the nontumorous liver. However, the efficacy of each of these therapies still needs to be evaluated in randomized controlled trials.     

Rectal injuries following radiation therapy for cervical cancer

Injuries of the rectal wall were examined up to 327 days in patients with uterus cancers after radiation therapy with 60Co gamma-rays. Various types of morphological changes were observed at the end of the therapy and the changes could be seen even 327 days after therapy with doses of 3,240-6,040 rad. The percentage of goblet cells in the rectal wall fluctuated for about 50 days after therapy and then became stable, but was slightly less than pre-irradiation level. The changes in the percentage seemed to represent radiation damages to the epithelial cells in the wall. The late effects in the blood vessels were probably more important than damages to the epithelial cells in the wall.