Goals of treatment, indication, and treatment for chronic hepatitis C

Hepatitis C virus (HCV) is a major cause of chronic hepatitis and hepatic fibrosis worldwide. Up to 85% of individuals infected with HCV develop chronic infection, which can progress to cirrhosis and hepatocellular carcinoma. The primary goal in the treatment of HCV infection is to reduce the mortality by preventing liver-related deaths associated with the development of hepatocellular carcinoma and decompensated cirrhosis. Pegylated interferons together with ribavirin are currently the standard of care for patients with chronic hepatitis. Here, I discuss the goals of treatment, indication and treatment of chronic hepatitis C.     

Early gastric cancer: diagnosis, pathology, treatment techniques and treatment outcomes

Recent improvements in endoscopic techniques and technologies and an increased understanding and recognition of the importance of early gastric cancer (EGC) will result in increases in the detection and diagnosis of precancerous or early cancerous lesions. The incidences of nodal metastasis of intramucosal and submucosal EGC are 3 and 20%, respectively. Therefore, major surgery may be inappropriate in many of these patients, and many cases of EGC may be treated by endoscopic mucosal resection (EMR). EMR was first introduced in Japan 20 years ago. Most EMR have been performed by the so-called 'strip biopsy' or EMR-C methods. However, we have sometimes experienced local recurrence in cases that had been resected in multiple fragments by these methods. To obtain 'complete resection', we developed the endoscopic submucosal dissection (ESD) technique using a special endoscopic knife, the insulation-tipped diathermic knife (IT knife). The rate of complete resection, i.e. cut margin free from cancer and one-piece resection, was remarkably higher for the IT knife technique than conventional EMR. ESD cases are increasing rapidly in Japan. EMR including ESD is a good method for patients with gastric cancer to preserve the stomach. For EMR, it is necessary to find EGC. Both diagnosis and treatment are important, and scientific data regarding lymph node metastasis and clinicopathological features are required.     

Hepatic coma--causes, recognition, treatment]

The name of the disease coma hepaticum is a collective notion for etiologically, pathologo-anatomically and biochemically different kinds of a failure of the function of the liver. A demarcation of different forms of the liver coma is necessary above all for prognostic and therapeutic reasons: hepatic disintegration coma, coma in hepatic failure, mixed coma, false hepatic coma, ferment block coma. Despite certain progress the therapeutic possibilities in hepatic coma cannot satisfy in recent years. Also the use of different, partly very expensive methods of the so-called liver substitute (exchange function and plasmapheresis, heterologous and homologous extracorporal liver perfusion, parasymbiotic crossed circulation, haemoperfusion with encapsulated activated charcoal, liver transplantation) up to now did not lead to a decisive improvement of the nearly infaust prognosis of the hepatic disintegration coma. Therefore preventing measures and careful control of endangered patients deserve particular attention.     

Aging, traumatic injury, and estrogen treatment

Aged subjects are more likely than young to have a poor prognosis after traumatic injury. Regardless of the type of injury, from scald wound to bone fracture, aged have slower recoveries and suffer more complications than their younger counterparts. This age-dependent phenomenon may be influenced by the hyper-inflammatory state observed in the aged referred to as 'inflamm-aging.' Having elevated levels of pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFalpha), in the circulation prior to injury may predispose the aged population to produce even higher concentrations of these factors after injury. Marked overproduction of pro-inflammatory cytokines leads to immunosuppression. Since many trauma victims do not die of their primary injuries, but rather succumb following infections and/or other complications at later time points, the functional status of the immune system is of paramount importance. Evidence suggests that at physiological levels, estrogen is beneficial to the immune system. This is due, in part, to the hormone's ability to boost immunity and to attenuate aberrant production of pro-inflammatory cytokines, thus serving as a systemic anti-inflammatory agent. In this short review, an examination of the effects of estrogen on inflammatory and immune responses that are critical to survival and recovery following traumatic injury will be discussed.     

Platypnoea-orthodeoxia syndrome. Diagnosis,etiology, treatment

Platypnoea-orthodeoxia (P.O.) syndrome is the association of dyspnoea and arterial oxygen desaturation aggravated in the erect position and relieved in the supine position. Initially considered very rare (20 cases reported over fifty years) and occurring essentially in patients having undergone pneumonectomy, it in fact occurs much more frequently if only it is looked for (20 extra cases reported in a single year). Some new aetiologies have been described, in particular dilatations or aneurysms of the ascending aorta. Diagnosis is made easier if the oxygen saturation is measured in the supine position when it is normal, and in the erect position when it falls considerably. Another argument is added by the small effect of inspiration of high concentrations of oxygen. Contrast echocardiography confirms the right-left shunt and allows estimation of the site. This is usually situated at the atrial level, via an inter-atrial communication or more often a patent foramen ovale; as a rule the area of dehiscence having been modified by the associated pathology allowing the right-left shunt despite normal right pressures. Exceptionally the shunt is situated at the vascular or pulmonary parenchymal level. Poor tolerance of P.O. syndrome justifies a therapeutic procedure; this is usually closure of the septal fault with an occluder introduced percutaneously; the results are generally highly spectacular.     

Photoaging: pathogenesis, prevention, and treatment

Premature skin aging, or photoaging, results largely from repeated exposure to ultraviolet (UV) radiation from the sun. Photoaging is characterized clinically by wrinkles, mottled pigmentation, rough skin, and loss of skin tone; the major histologic alterations lie in dermal connective tissue. In recent years, a great deal of research has been done to explain the mechanism by which UV induces dermal damage. This research has enabled the identification of rational targets for photoaging prevention strategies. Moreover, studies that have elucidated photoaging pathophysiology have produced significant evidence that topical tretinoin (all-trans retinoic acid), the only agent approved so far for the treatment of photoaging, also works to prevent it. This article summarizes evidence mainly from studies of human volunteers that provide the basis for the current model of photoaging and the effects of tretinoin.     

Prehypertension: Demographics,pathophysiology, and treatment

The term prehypertension, which first appeared in the Seventh Report of the Joint National Committee (JNC 7) in 2003, has sparked controversy in the field of hypertension. Systolic blood pressure (BP) rises with age in industrialized societies, but an individual’s rate of rise of systolic BP and the age at which BP crosses the arbitrary threshold of hypertension depends on prior BP levels (hence “prehypertension”). Obesity, another major factor in prehypertension, activates neurohumoral systems (renin-angiotensin and sympathetic nervous) and contributes to age-related BP increases. The JNC 7 recommendation for prehypertension management with optimal weight control (largely through diet and exercise) remains the mainstay, especially in the elderly. The Trial of Prevention of Hypertension demonstrated that angiotensin receptor blockade (ARB) retards age-related BP increases in prehypertensive patients. Associated elevated risk conditions (prediabetes, hypercholesterolemia, microalbuminuria) may justify early use of ARB therapy (in men and in women without childbearing potential) if weight control fails.     

Barrett carcinoma--diagnosis, screening, surveillance, endoscopic treatment, prevention

An adenocarcinoma of the distal esophagus may also be designated as Barrett's carcinoma as it evolves from Barrett's esophagus. Barrett's esophagus currently is defined as a columnar metaplasia of the distal esophagus, as identified by endoscopy, that, upon histopathology, is confirmed to contain intestinal metaplasia. A different histological entity of columnar metaplasia of the distal esophagus is cardia-type mucosa which probably precedes intestinal metaplasia, but lacks goblet cells typical for the latter. The conversion rate from Barrett's esophagus to Barrett's carcinoma amounts to 0.5 to 1 % per year. Patients with reflux symptoms should undergo early endoscopy in order to search for Barrett's esophagus (screening). In those cases where Barrett's esophagus is identified, regular endoscopic controls should be scheduled (surveillance). The intervals for this have been defined by recent consented guidelines. The aim is to detect neoplasia early. Neoplasia confined to the epithelium or mucosal layer can mostly be treated by endoscopic resection. The depth of infiltration, as determined by histopathology of the resected specimen, allows one to estimate the risk of lymph node metastasis, and therefore is crucial for the final judgment as to whether the endoscopic intervention may be considered curative. Individually, the risk of metastasis has to be weighed against the risk of morbidity and mortality conferred by the alternative surgical resection. The rapid increase of the incidence of Barrett's carcinoma in Western countries suggests that life style factors, in particular overweight, having a causal role. Data from interventional trials on prevention are, however, pending.     

Photoaging. Manifestations, prevention, and treatment

In recent years there has been an increasing awareness that many of the so-called attributes of aging skin are, instead, a reflection of environmental assault upon exposed areas of the body. Of special import are the deleterious effects of solar radiation on dermal connective tissue, leading to the visible manifestations of photoaging. Often termed "premature aging," the salient features of the process are distinctly different from those found in normal intrinsic aging. In general, chronically irradiated skin is metabolically hyperactive with epidermal hyperplasia and neoplasia, increased production of elastic fibers, GAGs, accelerated breakdown and synthesis of collagen, and enhanced inflammatory processes. In contrast, protected aged skin is usually characterized by a slow decline in many of these components. Experimental studies with animal models have confirmed the notion that the shorter, more energetic portion of the ultraviolet spectrum (UVB) is responsible for the dermal connective tissue destruction observed in photoaged skin. More recently, it has been shown that UVA and infrared radiation contribute significantly to photoaging, producing, among other changes, severe elastosis. Because the three broad wavebands are inseparably linked in terrestrial sunlight, all are of concern in the photoaging of human skin. Photoaged skin has been thought to be irreversibly damaged. However, our findings indicate that destruction and repair go on simultaneously under continued assault by actinic radiation. The balance is shifted toward repair when the radiation stress is relieved. Both epidermis and dermis are capable of moderate self-restoration when exogenous injury ceases, either by avoidance of sunlight or by the use of broad-spectrum, high-SPF sunscreens. Repair of the dermis, characterized by broad regions of new collagen deposited subepidermally, can be pharmacologically enhanced by topical application of retinoic acid. Although early protection from sunlight, before severe photodamage occurs, is most desirable, it is deemed advisable to counsel even older persons with photoaged skin to adopt protective measures, thereby allowing repair processes to occur.     

Pathophysiology, complications, and treatment of ascites

In the past few years, there have been important advances in the field of pathogenesis and management of ascites and spontaneous bacterial peritonitis in cirrhosis. A new pathogenic theory of ascites and renal dysfunction in cirrhosis has been presented, and previously ill-defined conditions, such as refractory ascites and hepatorenal syndrome, have been defined precisely. The reintroduction of therapeutic paracentesis has modified markedly the way in which patients hospitalized for ascites are treated. The use of potent and safe antibiotics has improved the resolution rate and survival of patients with spontaneous bacterial peritonitis, and the use of oral antibiotics will simplify the management of this condition in the near future. Finally, prophylactic antibiotic regimens represent a major step forward in the prevention of spontaneous bacterial peritonitis in subsets of cirrhotic patients with a great risk of developing this complication.     

Gastroparesis: symptoms, evaluation, and treatment

Gastroparesis presents with gastrointestinal symptoms and nongastrointestinal manifestations in association with objective delays in gastric emptying. The condition may complicate several systemic disorders or may be idiopathic in nature. The diagnosis is made by directed evaluation to exclude organic diseases, which can mimic the clinical presentation of gastroparesis coupled with quantification of gastric emptying. Current therapies rely on dietary modifications, medications to stimulate gastric evacuation, and agents to reduce vomiting. Endoscopic and surgical options are increasingly used for cases refractory to medication treatment.     

Osteonecrosis: etiology, diagnosis, and treatment

PURPOSE OF REVIEW: This review provides an update of the recent progress in etiology, pathogenesis, diagnosis, and treatment of osteonecrosis. RECENT FINDINGS: Concerning pathogenesis, there is evidence that there is a genetic predilection for those who are exposed to the two leading etiologic associations for osteonecrosis: corticosteroids and alcohol. Studies concerning the treatment of osteonecrosis indicate that most preservative (ie, joint-sparing) procedures available today have better results in the precollapse stages of the disease and in smaller lesions. Therefore, researchers continue to develop and modify diagnostic techniques, particularly relating to MRI, for the identification and quantification of osteonecrotic lesions. Advances concerning bone grafting and arthroplasty procedures have resulted in improved clinical outcomes for this patient population. The future treatment of osteonecrosis may involve genetic or cell-based therapies. SUMMARY: Although progress has been made, considerably more research is needed before we fully understand this disease. Hopefully, such research will lead to effective measures for saving the femoral head or, better yet, preventing osteonecrosis.