Future perspectives for acute promyelocytic leukemia therapy

Acute promyelocytic leukemia (APL) is the first leukemia where targeted therapy proved to be effective, as only patients with retinoic acid-sensitive APL leukemic-clones responded in vivo. The future perspectives of APL therapy should persist in targeting either the APL's cell-specific characteristics concerning differentiation, cell cycle, and survival potentials, or the molecular markers specific to the APL clone. Converging recent advances in cellular therapy and in scientific concepts of cell differentiation should aim toward a possible cure of APL.     

Diseases of the small intestine.

During the past 10 years considerable progress and increase of knowledge on small intestinal diseases has been achieved. This short review will cover some selected small bowel diseases including coeliac disease, Whipple's disease, rare congenital enteropathies, non-steroidal anti-inflammatory drug enteropathy and autoimmune enteropathy.     

Alcohol and absorption from the small intestine. 1. Impairment of absorption from the small intestine in alcoholics.

An absorption screen was performed in 10 chronic alcoholic patients within a few days of admission due to an acute alcoholic episode. Impaired absorption of d-Xylose was noted in three patients and low leucocyte ascorbic acid and serum folate levels in five. No abnormality was detected in jejunal histology. The absorption of water and electrolytes from the jejunum was studied in these patients using a triple-lumen tube perfusion system. The mean rate of absorption of water in the alcoholic subjects (50-0 +/- 2-3 ml/h) was significantly lower (P less than 0-001) than the mean value in 14 healthy control subjects (205 +/- 15-9 ml/h). A significant reduction of Na+ and Cl-absorption was also demonstrated in the alcoholic subjects. These results indicate that patients with acute-on-chronic alcoholism may have a function impairment of water and electrolyte absorption from the jejunum. This may, in part, account for some of the nutritional deficiencies in such patients and for symptoms such as diarrhoea which may be present.     

Future perspectives for hepatocellular carcinoma

BACKGROUND: Five facets of hepatocellular carcinoma (HCC) are identified that impact on future directions in the management of the disease: epidemiology, prevention, screening, diagnosis and therapy. Recent papers on HCC have been reviewed, and predictions have been made on developments in HCC over the next decade. DISCUSSION: It is predicted that hepatitis B-related HCC will decrease with vaccination, while hepatitis C-related HCC will become an increasing problem. Antiviral treatment and chemopreventive agents will prevent HCC development. Whole-population screening will not be an option, but screening is justified for individuals who can pay for it. There will be more emphasis on the use of tumour markers. Transabdominal ultrasound and triphasic spiral computed tomography will remain important radiological imaging techniques. The results of liver resection will not improve unless neoadjuvant/adjuvant therapy is proven to be effective. More patients with initially unresectable HCC will be down-staged to become resectable with improvements in local, regional and systemic therapies. Liver transplantation will be increasingly used. Local ablative therapy will improve the quality of survival but will have no impact on overall survival compared with surgical resection. The author hopes to review the accuracy of these predictions in 2013.     

Embryonic stem cells. Future perspectives

Embryonic stem cells (ES cells) are able to differentiate into any cell type, and therefore represent an excellent source for cellular replacement therapies in the case of widespread diseases, for example heart failure, diabetes, Parkinson's disease and spinal cord injury. A major prerequisite for their efficient and safe clinical application is the availability of pure populations for direct cell transplantation or tissue engineering as well as the immunological compatibility of the transplanted cells. The expression of human surface markers under the control of cell type specific promoters represents a promising approach for the selection of cardiomyocytes and other cell types for therapeutic applications. The first human clinical trial using ES cells will start in the United States this year.     

Endoscopic evaluation of the small intestine.

Technological achievements in the area of endoscope design and development have resulted in instruments capable of advancing beyond the reach of simple gastroscopes. Such instruments, known as enteroscopes, form the bases of small bowel endoscopy. Recent widespread use of enteroscopes have contributed significantly to the understanding of small intestinal pathology and improved the ability to diagnose and treat patients with intestinal bleeding sources.     

Alcohol and the small intestine

Several alterations of the small-intestinal morphology and function have been documented after alcohol ingestion. There are morphologic changes macroscopically and microscopically after acute alcohol administration in the proximal part of the small intestine, which are quickly reversible. There are no macroscopic changes and, in most patients, very discrete light microscopic changes in the small intestine after chronic alcohol ingestion. The ultrastructural changes are, however, profound, as seen by both transmission and scanning electron microscopy. The permeability is probably increased, permitting entrance of possible noxious agents, which may explain some of the extraintestinal tissue damage observed in chronic alcoholism. The transit is increased, at least after acute alcohol administration, perhaps contributing to the diarrhea commonly seen after heavy drinking. Several of the enzymes located in the brush border are affected; lactase activity can be depressed and perhaps result in a transient milk intolerance in predisposed individuals. The activity of GGT is increased and may partly account for the GGT elevation in serum after heavy drinking. Other enzymes, such as Na(+)-K(+)-ATPase, can be inhibited and result in a decreased absorption of substances that require active, energy-dependent transport mechanisms. The secretion of water and electrolytes may be increased (an effect on cAMP?). The absorption of several nutrients, vitamins, and other elements is disturbed. The bacterial flora is increased and changed, which may give rise to symptoms and also increase the production of acetaldehyde by bacterial metabolism of ethanol. Acetaldehyde is more toxic than ethanol, and an increased concentration of acetaldehyde can possibly accentuate the damage to the liver and other organs. The bacterial overgrowth can possibly cause endotoxinemia. Although studies on alcohol-related intestinal alterations have been relatively sparse, the acute and chronic effects of alcohol thus seem to be considerable. From available results it is, however, difficult to draw any definite conclusions about the clinical importance of many of the findings. Future research will need to study the relationship between, for example, the chronic morphologic changes, the absorptive dysfunction, and permeability alterations, on the one hand, and the gastrointestinal symptoms, the extraintestinal damage, and various deficiencies, on the other hand.