Age-related variations in gene expression patterns of renal cell carcinoma

Background

Clear cell renal cell carcinoma (ccRCC) is known to occur across the adult lifetime traversing the spectrum of age-related organismal changes. Little is known as to how the aging process may affect the course of renal cell carcinoma (RCC) and the repertoire of genes involved.

Juvenile progressive systemic sclerosis: report of five cases

Five cases of juvenile progressive systemic sclerosis (SSc) are reported (4 girls and 1 boy). The age of onset of the disease ranged from 4 to 13 years. The clinical features included Raynaud's phenomenon present in 4 of 5 cases; hyperpigmentation, skin tightening and contractures of the large joints were noted in all 5 cases. One patient initially diagnosed as having eosinophilic fasciitis developed SSc 3 months later. Another patient was diagnosed initially as having juvenile rheumatoid arthritis. There was one case of pulmonary fibrosis and another of mild restrictive lung disease. Two cases of esophageal and intestinal hypomotility were reported. Scleroderma nephropathy was absent in all 5 cases.     

The Value of Lung Injury Score in Assessing the Outcome of Patients with Rib Fracture

Background and Purpose:   

Management of rib fractures constitutes a major part of the trauma workload of any unit. Rib fractures result in disrupted chest wall mechanics and ventilatory insufficiency. The ability of a lung injury scoring system to predict the degree of respiratory dysfunction after rib fractures was evaluated.     

Long‐standing ulcerative colitis complicated by right subclavian artery occlusion and upper limbs arteriolitis with digital ischemia

A 48‐year‐old male patient with long‐standing ulcerative colitis since February 2001 which was diagnosed by endoscopy, developed acute digital ischemia affecting both hands with fixed colour changes in the left index finger which was followed shortly by digital ulceration. Magnetic resonance angiography (MRA) of both upper limbs showed evidence of vasculitis affecting digital arterioles on both sided and right subclavian occlusion. The patient received pulse methylprednisolone followed by cyclophosphamide pulse therapy, the latter continuing on a monthly basis for 6 months with appreciable improvement and remission of the vasculitic process; follow‐up MRA showed reperfusion of the previously occluded subcalvian artery. To the authors’ knowledge vasculitis complicating the course of ulcerative colitis is a rare association and is only sporadically reported in the literature. This rare entity should be diagnosed early and aggressively treated; MRA is a very promising diagnostic tool that is suitable for both diagnosis and follow‐up of patients with this rare entity.     

Chemoembolization in the therapy of hepatocarcinoma. A 3-year experience]

This study was aimed at evaluating the efficacy of chemoembolization (CE) to improve survival in patients with hepatocellular carcinoma (HCC). Our results were compared with the natural history of HCC. Sixty-two consecutive patients with HCC in Okuda's stages I and II underwent CE. Forty-seven patients were treated with CE alone; 9 patients had CE prior to surgery, and 6 patients had it after surgery because of recurrent HCC. One hundred and nine CEs (mean: 1.8 CEs/patient) were performed with Lipiodol UF, epirubicin and gelatin sponge. Actuarial survival was calculated considering Okuda's stage, neoplasm size, and evidence of pseudocapsule. The mean cumulative survival of the 47 patients treated with CE alone was 13.2 months; survival (+/- SE) at 12, 24 and 36 months was 0.75 (+/- 0.07), 0.46 (+/- 0.10) and 0.28 (+/- 0.12). Survival was not affected by Okuda's stage, neoplasm size, evidence of pseudocapsule (p > 0.05). Nevertheless, the patients with early HCC had better prognosis. Eighteen patients (42.9%) died during follow-up, 12 of whom (66.7%) from hepatic failure. The mean survival of patients with recurrence of HCC after surgery was 41 months (range: 24.8-74.9 months) since initial diagnosis of HCC, and 14.8 months (range: 7.1-29.6 months) since diagnosis of recurrence. Two of these patients died from hepatic failure. All the patients who underwent also surgery after CE are still alive (mean survival: 14.7 months). Histologic findings of resected specimens revealed viable neoplastic cells in all cases. Twenty-one major complications (20.2%) occurred in 18 patients (29%); the outcome of complications was favorable in all but one patient who died from sepsis. CE is a reliable and safe treatment for unresectable HCC. Small HCCs should be preferably treated with surgery or, alternatively, with percutaneous alcohol injection.     

Cancer by negative heterosis: breast and ovarian cancer excess in hybrids of inbred ethnic groups

Breast and ovarian cancer rates in Pakistan are significantly higher than in neighboring countries. The cancer rate discrepancies cannot be explained with discrepancies of their risk factors. We propose that observed cancer excess in Pakistan is due to cancer development by negative heterosis. Heterosis occurs when a hybrid has a phenotypic characteristic significantly different from that in either parent (hybrid vigor). At a molecular level, heterosis occurs in a heterozygote when one of the two alleles is inactivated. Gene inactivation occurs by methylation of cytosine in a promoter region of a gene. Initiation of allele inactivation is linked to the factors like stress, gender, diet, or another gene. In heterozygote, inactivation of one of the two tumor-suppressor alleles leads to monoallelic expression. This increases cancer risk in the same way the risk is increased in individual who inherit a single mutated tumor-suppressor gene (hereditary cancer syndrome). In both, cancer by heterosis and inherited cancer syndrome, cancer develops after inactivation of a second allele (second hit hypothesis). In a population, conditions that favor development of cancer by heterosis are those that favor mating of a large number of different homozygotes because they produce a large number of different heterozygotes. Among a large number of heterozygotes, there is an increased chance that some of hybrids will develop cancer by heterosis. In Pakistan, conditions were favorable for cancer development by heterosis because country has a high number of different ethnic groups and brotherhoods all of which have a higher rate of homozygosity due to a high frequency of consanguineous marriages, and marriages between members of different groups occurred because of intense population mixing. Result was birth of a large number of inter-ethnic/brotherhood hybrids (heterozygotes), some of which have developed cancer by heterosis.