Surgical approach and geriatric evaluation for elderly patients with colorectal cancer.

This review aims to define the most appropriate surgical approach and geriatric evaluation for elderly patients with colorectal cancer (CRC). Surgery represents the main treatment for CRC, but elderly cancer patients still represent a challenge for the surgeon due to frequent comorbidities such as cardiovascular and pulmonary diseases, which increase operative risk as well as the risk of postoperative morbidity and mortality. Cancer patients with comorbidities show lower survival rates and quality of life, together with higher healthcare costs. There is also evidence that patients with comorbidities sometimes receive modified treatment, compromising optimal care. To optimize treatment, the approach to elderly cancer patients needs a multidisciplinary team to assess preoperative conditions, prevent post-surgical complications and improve outcome, especially for frail patients. Laparoscopic surgery for CRC shows a number of advantages compared to conventional surgery such as less postoperative pain, rapid return to prior activities and a decrease in costs. Recent studies confirm that laparoscopic procedures could be performed safely on both older and younger patients with no difference compared with open surgery as regards morbidity or length of hospital stay.

Role of surgery for colorectal cancer in the elderly.

The prevalence of subjects with colorectal cancer is expected to grow in the next future decades and surgery represents the most successful treatment modality for these patients. Anyway, currently elderly subjects undergo less elective surgical procedures than younger patients mainly due to the high rates of postoperative morbidity and mortality. Some authors suggest extensive surgery, including multistage procedures, as carried out in younger patients while others promote less aggressive surgery. In older patients, laparoscopic-assisted colectomy showed a number of advantages compared to conventional open surgery that include lower stress, higher rate of independency after surgery, quicker return to prior activities and a decrease in costs. The recent advances in chemotherapy and the introduction of new surgical procedures such as the endoluminal stenting, suggest the need for a revisitation of surgical practice patterns and the role of palliative surgery, mainly for patients with advanced disease. In this article, we discuss the current role of surgery for elderly patients with colorectal cancer.

Autoimmunity in the elderly: Implications for cancer.

Immunosenescence is the aging process involving the immune system competencies. These changes imply a reduced level of immunosurveillance against cancer onset and the occurrence of autoimmune phenomena. The clinical presentation of autoimmune diseases in the elderly is characterized in most cases by atypical features, insidious presentation and poor specificity of laboratory parameters. The role of autoimmune reactivity in the elderly either as a consequence of or as a risk factor for cancer development has aroused great interest among clinicians and researchers, as well as the influence of a chronic inflammatory state as a predisposing factor for autoimmunity and cancer occurrence. Particularly, we have investigated the pathogenetic effect of two cell subsets, Treg cells and Th17 lymphocytes, involved in the control mechanisms both of autoimmune reactions and cancer onset, as the possible future approach to treat cancer in older adults.

Chromogranin A (CgA) serum level as a marker of progression in hepatocellular carcinoma (HCC) of elderly patients.

The observation of neuroendocrine (NE) activity during clinical course of hepatocellular carcinoma (HCC), suggested the use of NE serum markers to detect it. Thus we have evaluated the usefulness of serum measurements of CgA in monitoring disease activity of HCC. We investigated the role of serum concentrations of CgA, alpha-fetoprotein (AFP) and des-gamma-carboxyl-prothrombin (DCP) in 55 patients with HCC, 27 patients with cirrhosis, 22 patients with chronic hepatitis and a control group of 20 volunteers and the relationship between the pre-treatment serum CgA and clinical stages of the disease. CgA was significantly higher in the patients affected by HCC as compared with those affected by either hepatitis or cirrhosis (p<0.001). We also observed significant differences, comparing CgA serum levels in the tumor classes T1-T4: T1 vs. T2 (p<0.001), T1 vs. T3 (p<0.001), T1 vs. T4 (p<0.001), T2 vs. T3 (p<0.001), T2 vs. T4 (p<0.001) and T3 vs. T4 (p<0.001). CgA levels were significantly higher in poorly differentiated HCC vs. well differentiated (p<0.05) and medium differentiated ones (p<0.001). Also the comparison between Child-Pugh degree A and C showed a significant difference in CgA levels (p<0.001). Thereby, patients with higher CgA level had poor survival and showed poor prognosis, compared to those with lower CgA level, i.e., the CgA is useful in monitoring progression of disease and may assist as a prognostic indicator.

The role of immunity in elderly cancer.

The increased incidence of malignancies in elderly patients living in industrialized countries has led to both identify the causes that alter the normal homeostatic balance in elderly and designate the specific treatments. The progressive decline of the immune system (immunosenescence) involving cellular and molecular alterations impact both innate and adaptive immunity. The immunosenescence leads to increased incidence of infectious diseases morbidity and mortality as well as heightened rates of other immune disorders such as autoimmunity, cancer, and inflammatory conditions. Here, we summarize the knowledge on the major changes in the immune system associated with aging in primary lymphoid organs as well as a description of molecular mechanisms, and the impact on cancer development.

Elevated chromogranin A (CgA) serum levels in the patients with advanced pancreatic cancer.

The neuroendocrine differentiation in PC could potentially represent a new finding with diagnostic, prognostic and therapeutic implications. This study aimed at evaluating the clinical usefulness of CgA as a neuroendocrine (NE) serum-marker. We investigated the role of the serum concentration of CgA in a study group of patients with PC. CgA was significantly higher in the patients affected by PC as compared with the group of healthy subjects (HS) and those with chronic pancreatitis (CHP) (p<0.001). Also the HS group differed significantly from the CHP control group in the serum CgA levels (p<0.001). The serum carbohydrate antigen (CA19-9) level displayed a significant difference (p<0.001) between the PC and the HS group. The PC and CHP groups, as well as the HS and CHP groups showed also significant differences in the CA19-9 levels (p<0.001). One can conclude that the patients with higher CgA levels had poorer prognosis and survival, as compared to those with lower CgA levels. These results support the notion that the determination of serum CgA level before treatment may be a potential prognostic factor for PC.

Acetyl-L-carnitine treatment in minimal hepatic encephalopathy.

Minimal hepatic encephalopathy (MHE) is characterized by disturbance of mental state and neuromuscular function. To assess the clinical efficacy of acetyl-L: -carnitine (ALC) in the treatment of MHE, we performed a randomized, double-blind, placebo-controlled study administering ALC in cirrhotic patients with this disease and evaluating their cognitive functions. One hundred and twenty-five cirrhotic patients, of whom 21 were infected by hepatitis B virus, 75 by hepatitis C virus and 29 with cryptogenic cirrhosis, were enrolled in our study. Patients were randomly divided into two groups, and using double-blind administration, group A was treated with ALC and group B with placebo for 90 days. The two groups were similar in demographic characteristics, aetiology of cirrhosis, duration and Child-Pugh grade. Minimal hepatic encephalopathy was diagnosed with the Trail Making Test (TMT), Symbol Digit Modalities Test (SDMT) and Auditory Verbal Learning Test (AVL) and cognitive function with the Mini Mental State Examination (MMSE). After 90 days in group A treated with ALC, we observed a significant decrease in prothrombin time (P < 0.001), bilirubin serum levels (P < 0.01), AST (P < 0.001), fasting NH(4) serum levels (P < 0.001), Trail Making Test-A (P < 0.001) and Trail Making Test-B (P < 0.001), and a significant increase in albumin serum levels (P < 0.005), MMSE test (P < 0.001), Symbol Digit Modalities Test (P < 0.001), BDT (P < 0.001), AVL long-term test (P < 0.001) and AVL total test (P < 0.001). No significant differences were observed in EEG in either group of patients treated with ALC or placebo. The benefits of ALC in comparison with placebo are demonstrated in greater reductions in serum ammonia levels, as well as in improvements of neuropsychological functioning.

L-carnitine treatment reduces steatosis in patients with chronic hepatitis C treated with alpha-interferon and ribavirin.

BACKGROUND: Hepatic steatosis is a common presentation in patients with chronic hepatitis C. Interferon alpha exerts both antiviral and immunomodulating actions, and influences on lipid metabolism. The aim of our study was to test whether L-carnitine reduces steatosis in patients treated with interferon and ribavirin. PATIENTS AND METHODS: A total of 70 patients were randomly assigned to receive either leucocyte IFN alpha at a dose of 3 MIU thrice a week plus 1,000 mg ribavirin per day for 12 months (group A) or IFN alpha and ribavirin at the same dose plus 2 g carnitine per day (group B). RESULTS: Comparison of the two treatments showed significant differences between the mean values of the following parameters at the end of the treatment: ALT -68 vs -95 IU/ml (P < 0.05), total cholesterol 0.08 vs -0.91 mmol/l (P < 0.05) and triglycerides +0.25 vs -20 mmol/l (P < 0.05); and at the follow-up: AST -35 vs -65 IU/ml (P < 0.05) and ALT -55 vs -84 IU/ml (P < 0.05). All values were lower in group B (IFN + Ribavirin + Carnitine) than in group A (IFN plus Ribavirin). When comparing those patients treated with IFN + ribavirin with those treated with IFN plus ribavirin plus carnitine, the response at the end of the treatment was 48% vs 56%, and the sustained response 39% vs 46%, respectively. CONCLUSIONS: Combined treatment with L: -carnitine, ribavirin and IFN alpha resulted in greater antihyperlipidaemic effects and than with ribavirin and IFN alpha alone. The results of this study suggest that L: -carnitine may have a role among the reduction of steatosis strategies in patients with hepatitis C treated with IFN alpha and ribavirin.

Acetyl L-carnitine (ALC) treatment in elderly patients with fatigue.

Fatigue is one of the conditions most frequently complained by the elderly. There are few effective treatment options for patients with chronic fatigue syndrome. To determine the efficacy, tolerability and impact on the fatigue, as well as on cognitive and functional status of elderly subjects with acetyl L-carnitine (ALC), 96 aged subjects (>70 years, range 71-88) were investigated (50 females and 46 males; mean age 76.2+/-7.6 and 78.4+/-6.4 years, respectively). They met four or more of the Holmes major criteria or at least six of Fukuda minor criteria. Fatigue was measured with the Wessely and Powell [Wessely, S., Powell, R., 1989. Fatigue syndromes: a comparison of chronic postviral fatigue with neuromuscular and affective disorders. J. Neurol. Neurosurg. Psychiatry 52, 940-948] scores, with the fatigue severity scale. At the end of the treatment, we observed a decrease of physical fatigue: 6.2 (p<0.001), of mental fatigue: 2.8 (p<0.001), of severity fatigue: 21.0 (p<0.001) and improvements in functional status: 16.1 (p<0.001) and cognitive functions: 2.7 (p<0.001). By the end of the treatment, significant differences between the two groups were found for the following parameters: muscle pain -27% versus -3% (p<0.05); prolonged fatigue after exercise: 51% versus -4% (p<0.0001); sleep disorders: 28% versus 4% (p<0.05); physical fatigue: 7 versus -0.5 (p<0.0001); mental fatigue: -3.3 versus 0.6 (p<0.0001); fatigue severity scale: -22.5 versus 1.2 (p<0.0001); functional status 17.1 versus 0.6 (p<0.0001); mini mental state examination (MMSE) improvements: 3.4 versus 0.5 (p<0.0001). Our data show that administering ALC may reduce both physical and mental fatigue in elderly and improves both the cognitive status and physical functions.