Acute myeloid leukemia following Hodgkin lymphoma: a population-based study of 35,511 patients

Treatments for Hodgkin lymphoma are associated with large relative risks of acute myeloid leukemia (AML), but there are few estimates of the excess absolute risk (EAR), a useful measure of disease burden. One-year Hodgkin lymphoma survivors (N = 35,511) were identified within 14 population-based cancer registries in Nordic countries and North America from January 1, 1970, through December 31, 2001. We used Poisson regression analysis to model the EAR of AML, per 10,000 person-years. A total of 217 Hodgkin lymphoma survivors were diagnosed with AML (10.8 expected; unadjusted EAR = 6.2; 95% confidence interval = 5.4 to 7.1). Excess absolute risk for AML was highest during the first 10 years after Hodgkin lymphoma diagnosis but remained elevated thereafter. In subsequent analyses, adjusted for time since Hodgkin lymphoma diagnosis and presented for the 5-9 year interval, the EAR was statistically significantly (P < .001) larger in patients diagnosed with Hodgkin lymphoma at age 35 years and older than in those diagnosed before 35 years of age. The EAR of AML declined statistically significantly after 1984 (7.0 to 4.2 and 16.4 to 9.9 in the < 35 and > or = 35 age groups, respectively), which may be associated with modifications in chemotherapy.     

Risk of second cancer among women with breast cancer

A large number of women survive a diagnosis of breast cancer. Knowledge of their risk of developing a new primary cancer is important not only in relation to potential side effects of their cancer treatment, but also in relation to the possibility of shared etiology with other types of cancer. A cohort of 525,527 women with primary breast cancer was identified from 13 population-based cancer registries in Europe, Canada, Australia and Singapore, and followed for second primary cancers within the period 1943-2000. We used cancer incidence rates of first primary cancer for the calculation of standardized incidence ratios (SIRs) of second primary cancer. Risk of second primary breast cancer after various types of nonbreast cancer was also computed. For all second cancer sites combined, except contralateral breast cancer, we found a SIR of 1.25 (95% CI = 1.24-1.26) on the basis of 31,399 observed cases after first primary breast cancer. The overall risk increased with increasing time since breast cancer diagnosis and decreased by increasing age at breast cancer diagnosis. There were significant excesses of many different cancer sites; among these the excess was larger than 150 cases for stomach (SIR = 1.35), colorectal (SIR = 1.22), lung (SIR = 1.24), soft tissue sarcoma (SIR = 2.25), melanoma (SIR = 1.29), non-melanoma skin (SIR = 1.58), endometrium (SIR = 1.52), ovary (SIR = 1.48), kidney (SIR = 1.27), thyroid gland (SIR = 1.62) and leukaemia (SIR = 1.52). The excess of cancer after a breast cancer diagnosis is likely to be explained by treatment for breast cancer and by shared genetic or environmental risk factors, although the general excess of cancer suggests that there may be additional explanations such as increased surveillance and general cancer susceptibility.     

A pooled analysis of second primary pancreatic cancer

Studies of pancreatic cancer in the setting of second primary malignant neoplasms can provide etiologic clues. An international multicenter study was carried out using data from 13 cancer registries with a registration period up to year 2000. Cancer patients were followed up from the initial cancer diagnosis, and the occurrence of second primary malignant neoplasms was compared with expected values derived from local rates, adjusting for age, sex, and period of diagnosis. Results from individual registries were pooled by use of a fixed-effects model. People were at higher risk of developing pancreatic cancer within 10 years of a diagnosis of cancers of the pharynx, stomach, gallbladder, larynx, lung, cervix, corpus uteri, bladder, and eye and 10 years or later following a diagnosis of cancers of the stomach, colon, gallbladder, breast, cervix, placenta, corpus uteri, ovary, testis, bladder, kidney, and eye, as well as Hodgkin's and non-Hodgkin's lymphomas. Pancreatic cancer was connected with smoking-related cancers, confirming the etiologic role of tobacco. The associations with uterine and ovarian cancers suggest that reproductive factors might be implicated in pancreatic carcinogenesis. The elevated pancreatic cancer risk in young patients observed among several types of cancer implies a role of genetic factors. Radiotherapy is also suggested as a risk factor.     

Vitamin B12 Metabolism in Myelomatosis

In 38 patients with myelomatosis the serum cobalamin varied from 34 pmol/l to 404 pmol/l, median 181.5 pmol/l, which is significantly lower than the levels in 22 control persons with range 173–535 pmol/l, median 265 pmol/l. In spite of low serum cobalamin no symptoms of vitamin B₁₂ deficiency could be demonstrated in any of the patients, except for the one patient who had a serum cobalamin of 34 pmol/l. Mean values for Hb, MCV, PCV, serum lactate-dehydrogenase, adjusted red cell folate and nucleated neutrophil count were similar in a group of patients with a serum cobalamin below 160 pmol/l and a group of patients with higher serum cobalamin values. The decrease in serum cobalamin is due in part to a reduction in the major cobalamin binder (TC-I) in serum. Measuring serum cobalamin in relationship to gastric acid secretion, we found a significantly higher frequency of hypo- and achlorhydria in patients with serum cobalamin below 160 pmol/l although the intestinal absorption of vitamin B₁₂ was normal by a Schilling test. Although our finding of low saturation of TC-I in serum seems to demonstrate decreased vitamin B₁₂ content in the body in myelomatosis, the lack of evidence for a functional vitamin B₁₂ deficiency speaks against giving a supplement to patients with myelomatosis.     

Trocar cystostomy during transurethral prostatic resection

A new suprapubic trocar for constant drainage of irrigating fluid during transurethralresection of the prostate was studied in 87 patients: The irrigating fluid height was 60 cm. above the prostatic fossa in 61 patients and 40 cm. in 26 patients. The absorption of irrigating fluid during resection was measured by volumetric and radioisotopic methods and was compared with and without use of trocar in the two patient groups. In the 40-cm. group, but not in the 60-cm. group, the use of trocar cystostomy lowered the total as well as the intravascular absorption of irrigating fluid to low and clinically insignificant amounts. The low bladder pressure (average 8 cm.) explained the low absorption. The use of the trocar in this group also resulted in lower blood loss per gram resected tissue and less operating time per gram tissue removed. Use of the trocar in transurethral prostatic resection represents a technical advantage over conventional techniques, since it allows uninterrupted resection at a low bladder pressure.     

Some dualistic properties of the cochlear microphonic

Within a small frequency range just above the characteristics frequency of a differential electrode pair, cochlear microphonic input-output functions are bimodal, exhibiting two maxima. The more sensitive, low-intensity response has a more limited linear operating range, and it is more labile due to acoustic fatigue or hypoxia. After fatigue or hypoxia, the high-intensity response is revealed. The latter operates 180° out-of-phase with the former, presumably due to its being generated more basalward in the cochlea. The difference in the lability of the two components suggests that the two sources are different types of hair cells; i.e. outer and inner hair cells.     

Diffuse Lymphosarcomatous Infiltration in the Central Nervous System

Massive lymphosarcomatous infiltration, confirmed at autopsy, occurred in a 46-year-old man with neurological signs rapidly progressing to total paralysis of peripheral as well as cranial nerves. These signs set in at a time when the malignant systemic disease seemed to be otherwise in remission, and indeed they gave rise to great differential diagnostic difficulties.     

Differential capacities for DNA repair in Clara cells, alveolar type II cells and macrophages of rabbit lung

The ability to repair damaged DNA was determined in differentcell populations of rabbit lung cells isolated by centrifugalelutriation. DNA excision repair, measured as unscheduled DNAsynthesis, was examined in in vitro confluent primary cultures.A dose dependent level of DNA excision repair was observed inalveolar type II cells after exposure to the direct acting alkylatingagents N-methyl N'-nitro-N-nitrosoguanidine, N-ethyl-N-nitrosoureaand methyl methanesulphonate. Furthermore, O⁶-alkylguanine-DNAalkyltransferase activity was easily detectable in alveolartype II cells and alveolar macrophages. In contrast, non-ciliated(Clara) cells had 4 to 20-fold lower levels of DNA excisionrepair and non-detectable levels of O⁶-alkylguanine-DNA alkyltransferase.Uracil-DNA glycosylase activities in Clara cells and alveolartype II cells were in the same range and had 3-fold lower activitythan alveolar macrophages. Our findings indicate that variouslung cells differ in DNA repair capacity and may thus differin sensitivity to some carcinogens.     

Smokeless tobacco use and risk of cancer of the pancreas and other organs

Little information is available on the role of tobacco, alcohol and diet in the survival of upper aero digestive cancers. Our study analysed the survival of 931 laryngeal and hypopharyngeal cancer patients, enrolled in a population based case-control study conducted at 5 centres in southeast Europe during 1979-1982. Age at the time of diagnosis and site of origin of tumour were observed to be predictors of the survival. Cigarette smoking, and to a limited extent alcohol drinking, before the diagnosis of tumour seem to influence the overall survival whereas high intakes of vegetables and vitamin C were observed to favourably affect the prognosis. For mortality from upper aerodigestive cancer protective effects of high intakes of vegetables, fibres and vitamin C were observed. Our results support the hypothesis that there is a role for dietary intervention to improve survival of laryngeal and hypopharyngeal cancer patients.