Early detection and prevention of pancreatic cancer: Is it really possible today?

Pancreatic cancer is the 4th leading cause of cancerrelated death in Western countries.Considering the low incidence of pancreatic cancer,population-based screening is not feasible.However,the existence of a group of individuals with an increased risk to develop pancreatic cancer has been well established.In particular,individuals suffering from a somatic or genetic condition associated with an increased relative risk of more than 5-to 10-fold seem to be suitable for enrollment in a surveillance program for prevention or early detection of pancreatic cancer.The aim of such a program is to reduce pancreatic cancer mortality through early or preemptive surgery.Considering the risk associated with pancreatic surgery,the concept of preemptive surgery cannot consist of a prophylactic removal of the pancreas in high-risk healthy individuals,but must instead aim at treating precancerous lesions such as intraductal papillary mucinous neoplasms or pancreatic intraepithelial neoplasms,or early cancer.Currently,results from clinical trials do not convincingly demonstrate the efficacy of this approach in terms of identification of precancerous lesions,nor do they define the outcome of the surgical treatment of these lesions.For this reason,surveillance programs for individuals at risk of pancreatic cancer are thus far generally limited to the setting of a clinical trial.However,the acquisition of a deeper understanding of this complex area,together with the increasing request for screening and treatment by individuals at risk,will usher pancreatologists into a new era of preemptive pancreatic surgery.Along with the growing demand to treat individuals with precancerous lesions,the need for low-risk investigation,lowmorbidity operation and a minimally invasive approach becomes increasingly pressing.All of these considerations are reasons for preemptive pancreatic surgery programs to be undertaken in specialized centers only.     

Noninvasive diagnosis of esophageal varices: is it feasible?

The possibility of identifying cirrhotic patients with esophageal varices by noninvasive means is attractive, because it would allow for the restriction of the performance of screening endoscopy to patients at high risk of having varices. Over the years, several studies addressing this issue have been performed with little success. The recently proposed platelet count/spleen diameter ratio appears to be the best noninvasive predictor of esophageal varices developed so far. However, the available evidence is not yet sufficient to allow for the modification of the current policy of screening cirrhotic patients by endoscopy at the time of diagnosis to detect varices.     

Reversal of heart failure remodeling: Is it maintained?

BACKGROUND: Reversal of heart failure remodeling has been observed with intensive heart failure therapy. HYPOTHESIS: We hypothesized that reversal of heart failure remodeling may not be sustained in long-term follow-up. METHODS: Sixty-one sequential patients with heart failure and left ventricular ejection fraction < or = 35%, who improved their ejection fraction by > or = 10% over baseline at follow-up, were prospectively followed and retrospectively analyzed. Each patient underwent echocardiography at baseline and biannually thereafter. RESULTS: In all patients, left ventricular ejection fraction increased from 18 +/- 7% to 42 +/- 12% on uptitrated medical therapy. At follow-up over 20 +/- 8 (+/- standard deviation) months, this improvement was sustained in 38 patients ("Improved"). A relapse in remodeling occurred in the remaining 23 patients ("Relapsed"), with ejection fraction falling to 24 +/- 7%. For Improved and Relapsed patients, baseline echocardiographic and clinical parameters were equivalent. However, Improved patients tended to be younger, with shorter heart failure duration. Improved patients had more effective improvement in ejection fraction than Relapsed patients (45 +/- 13% vs. 36 +/- 8%, p = 0.005), with greater reductions in chamber size and mitral regurgitation. CONCLUSION: Reversal of heart failure remodeling may be sustained in only two-thirds of patients at long-term follow-up. In contrast to Relapsed patients, Improved patients tended to be younger, with shorter heart failure duration and a more complete recovery of left ventricular systolic function.     

Differentiation of rat marrow mesenchymal stem cells into pancreatic islet beta-cells

AIM:To explore the possibility of marrow mesenchymalstem cells(MSC)in vitro differentiating into functional islet-like cells and to test the diabetes therapeutic potency ofIslet-like cells.METHODS:Rat MSCs were isolated from Wistar rats andcultured.Passaged MSCs were induced to differentiate intoislet-like cells under following conditions:pre-induction withL-DMEM including 10 mmol/L nicotinamide l mmol/Lβ-mercaptoethanol 200 mL/L fetal calf serum(FSC)for 24 h,followed by induction with serum free H-DMEM solution including10 mmol/L nicotinamide l mmol/L,β-mercaptoethanol for10 h.Differentiated cells were observed under inversemicroscopy,insulin and nestin expressed in differentiatedcells were detected with immunocytochemistry.Insulinexcreted from differentiated cells was tested withradioimmunoassay.Rat diabetic models were made to testin vivo function of differentiated MSCs.RESULTS:Typical islet-like clustered cells were observed.Insulin mRNA and protein expressions were positive indifferentiated cells,and nestin could be detected in pre-differentiated cells.Insulin excreted from differentiatedMSCs(446.93±102.28 IU/L)was much higher than thatfrom pre-differentiated MSCs(2.45±0.81 IU/L(P<0.01).Injected differentiated MSCs cells could down-regulateglucose level in diabetic rats.CONCLUSION:Islet-like functional cells can be differentiatedfrom marrow mesenchymal stem cells,which may be anew procedure for clinical diabetes stem-cell therapy,thesecells can control blood glucose level in diabetic rats.MSCsmay play an important role in diabetes therapy by isletdifferentiation and transplantation.     

Allogeneic stem cell transplantation for relapsed primary central nervous system lymphoma: Is it feasible?

Primary central nervous system lymphoma (PCNSL), has an aggressive course and in untreated patients median survival is limited to three months. For relapsed PCNSL, the treatment options are few and results are usually unsatisfactory. Allogeneic Hematopoietic Stem Cell Transplantation (allo-HCT) has been widely used for treatment of relapsed/refractory NHL patients. However there are limited data whether graft versus lymphoma effect can work in PCNSL patients. Here, we present a relapsed refractory PCNSL case treated by allo-HCT.     

Ten years of life: Is it a matter of choice?

BACKGROUND: Relative risk estimates suggest that effective implementation of behaviors commonly advocated in preventive medicine should increase life expectancy, although there is little direct evidence. OBJECTIVE: To test the hypothesis that choices regarding diet, exercise, and smoking influence life expectancy. METHODS: A total of 34 192 California Seventh-Day Adventists (75% of those eligible) were enrolled in a cohort and followed up from 1976 to 1988. A mailed questionnaire provided dietary and other exposure information at study baseline. Mortality for all subjects was ascertained by matching to state death tapes and the National Death Index. RESULTS: California Adventists have higher life expectancies at the age of 30 years than other white Californians by 7.28 years (95% confidence interval, 6.59-7.97 years) in men and by 4.42 years (95% confidence interval, 3.96-4.88 years) in women, giving them perhaps the highest life expectancy of any formally described population. Commonly observed combinations of diet, exercise, body mass index, past smoking habits, and hormone replacement therapy (in women) can account for differences of up to 10 years of life expectancy among Adventists. A comparison of life expectancy when these factors take high-risk compared with low-risk values shows independent effects that vary between 1.06 and 2.74 years for different variables. The effect of each variable is assessed with all others at either medium- or high-risk levels. CONCLUSIONS: Choices regarding diet, exercise, cigarette smoking, body weight, and hormone replacement therapy, in combination, appear to change life expectancy by many years. The longevity experience of Adventists probably demonstrates the beneficial effects of more optimal behaviors.     

Central blood pressures: do we need them in the management of cardiovascular disease? Is it a feasible therapeutic target?

It is well established that in young and healthy individuals central (aortic or carotid) systolic and pulse pressures are different from peripheral (brachial) corresponding pressures as a consequence of progressive changes in arterial stiffness and pressure wave reflections along the arterial tree. There is evidence indicating that in interventions with pharmaceutical and non-pharmaceutical agents, central pressures are subjected to greater changes than peripheral pressures, and they are more closely related to the pathophysiology of end-organ damage or cardiovascular risk. Therefore central blood pressures may be of higher clinical importance than peripheral pressures. The present review aims to provide an insight into the (patho)physiology of central blood pressures, to present the most accurate techniques for their estimation, and to discuss the available experimental and epidemiological data that support the emerging need for the evaluation of central blood pressures in clinical practice.     

Is tailored therapy feasible in oncology?

Tailored therapy aims to cure a patient who suffers from a specific disease with an effective and safe drug, based on the complex interactions among patient's characteristics, disease physiopathology and drug metabolism. Genomic and proteomic technologies represent promising new useful tools to understand cancer biology and molecular basis of interindividual differences of anticancer drugs efficacy. Genomic profiling seems to be able to re-classifying cancer into new molecular and prognostic homogeneous subgroups. By individual polymorphisms it is possible to identify the patients at higher risk for severe toxicity from those that may gain benefit from a particular treatment. The clinical use of targeted therapy is hampered by several questions, including: optimal biological dose, availability of surrogate biomarkers predictive of activity, schedule of administration, tumor histotype and stage to treat and modalities of combination with chemo/radiotherapy. In addition, further efforts are needed to improve the reliability of genomic and proteomic technologies. These unsolved issues presently make tailored therapy an open challenge.