Inflammation, aging, and cancer vaccines

Immunosenescence is characterized by a series of changes of immune pathways, including a chronic state of low-grade inflammation. Mounting evidence from experimental and clinical studies suggests that persistent inflammation increases the risk of cancer and the progression of the disease. Cancer vaccination, which came into view in the last years as the most intriguing means of activating an immune response capable of effectively hampering the progression of the preclinical stages of a tumour, has been shown to be less effective in older age than in young adults. Available evidence on the use of inhibitors of inflammation has indicated their potential enhancement of cancer vaccines, suggesting the possibility to improve the low effectiveness of cancer vaccines in old age employing pharmacological or natural compounds-based anti-inflammatory intervention. This review addresses the effects of age and inflammation on cancer development and progression, and speculates as to whether the modulation of inflammation may influence the response to cancer immunization.     

Lung metastasectomy in colorectal cancer: Is this surgery effective in prolonging life?

The commonest context in which pulmonary metastasectomy is performed is for recurrent colorectal cancer. With a more active policy of surveillance among cancer teams, ready access to ever faster CT scans and a willingness to perform further surgery to control recurrent cancer, the practice of pulmonary metastasectomy is increasing. In this pro/con debate the issues are explored. It is recognized by both sides that there is no randomized trial evidence on which to base the practice. The difference of opinion is whether there is sufficient evidence from very many case series of both pulmonary and hepatic metastasectomy on which to base current practice. The surgeon's view is that the weight of evidence from many follow‐up studies is in favour of continuing this practice. The mathematician's view is that case selection could account for nearly all the observed results.     

NEPHROBLASTOMA. DNA CHARACTERISTICS AND THEIR MODIFICATIONS INDUCED BY PRENEPHRECTOMY CHEMOTHERAPY: A CYTOFLUORIMETRIC STUDY

Treatment of nephroblastoma (Wilms' tumor) has presently achieved a 90% survival rate. Stage and grade are considered the most reliable prognostic parameters, but other biological factors are under study in order to improve patient stratification. Deoxyribonucleic acid (DNA) ploidy has been suggested to be useful in this setting. We retrospectively studied 79 patients with nephroblastoma (58 pretreated with chemotherapy and 21 not pretreated) by means of flow cytometry. DNA content and synthetic phase values were correlated with pathologic features and outcome. DNA modifications induced by chemotherapy were investigated. Sixty-nine tumors were diploid and 10 aneuploid. DNA content did not correlate with clinical course and was not modified by pretreatment. Aneuploid tumors were restricted to lower stages. Mean S-phase rate was lower and did not vary according to histology in pretreated tumors, while it was higher and increased with grade (p = 0.007) in previously untreated tumors. The fraction of cells in synthetic activity was related to outcome: Patients whose tumors displayed higher S-phase rates had a more favorable clinical course. Ploidy did not appear to be of prognostic significance. S-phase rate decreased after chemotherapy (p = 0.0002) and was related to survival. The worse outcome of pretreated patients might be attributed to a minor sensitivity to postoperative treatment: Preoperative chemotherapy would decrease the cell proliferation and might select resistant cellular clones of (possible) neoplastic residues.     

Metachronous bilateral Wilms' tumor

Wilms' tumor occurs in 5-10 % of all cases of nephroblastoma. The metachronous form represents 2-3 % of cases. Most (96.2 %) metachronous tumors appear within the first 5 years of the primary tumor. Associated malformations are more common in bilateral cases. Metachronous tumors are a therapeutic challenge. We describe the case of an 11-year-old girl with left hemihypertrophy. The diagnosis was metachronous relapse of Wilms' tumor 7 years after the first diagnosis. The patient received five courses of preoperative chemotherapy and tumorectomy was performed. Because of post-surgical complications, nephrectomy was performed on her only kidney. Since she is anephric, the patient is in chronic renal failure and is dependent on dialysis. Treatment with carboplatin and etoposide was continued after surgery and the patient is currently in complete remission. The appearance of a metachronous Wilms' tumor 5 years after that of the primary tumor is rare. When a contralateral tumour develops, chemotherapy must be given until the size of the tumor is reduced in order to preserve renal function and avoid dialysis. In patients with chronic renal failure caused by bilateral nephrectomy, ongoing treatment with dialysis support can be achieved through the choice of effective drugs and knowledge of their pharmacokinetics and pharmacodynamics.