Seminars in gastrointestinal disease最新文献

Adenocarcinoma of the pancreas is the fifth most common cause of cancer death in the United States. It affects men and women fairly equally and is most frequently diagnosed in the eighth decade of life. It may occur as part of hereditary/familial pancreatitis with an identified genetic mutation, and smokers are at increased risk. Cancer most often occurs in the pancreatic head and often leads to biliary obstruction with a clinical presentation of painless jaundice. The principal diagnostic modality is dedicated pancreatic computed tomography (CT) scanning, although other imaging techniques have a role. Endoscopic retrograde cholangiopancreatography (ERCP) is generally reserved for obtaining tissue, for which it is insensitive, or for palliative stenting. Surgery with the Whipple procedure offers the only chance of cure. Patients are staged as resectable if there are no distant metastases to lymph nodes or organs and there is no major vessel involvement. The 5-year survival rate for resectable patients is about 10% with a median survival of 12 to 18 months. Unresectable patients live about 6 months. Adjuvant chemotherapy with 5-fluorouracil (5-FU) or gemcitabine provides modest benefits. Palliative biliary decompression, pain control, and maintenance of gastric drainage are the usual forms of therapy.

Adenocarcinoma of the esophagus and gastric cardia are the most rapidly increasing cancers in developed countries. Adenocarcinoma of the esophagus is associated with chronic gastroesophageal reflux, and Barrett's esophagus is a precursor. This disease most frequently affects middle-aged white men. Endoscopic surveillance should be performed on patients with Barrett's esophagus, and esophagectomy is often performed on persons with high-grade dysplasia. Ablation of Barrett's esophagus has been proposed to prevent cancer but the outcomes are unproven. Squamous carcinoma of the esophagus most often affects black men and is associated with alcohol and tobacco use. The diagnosis of esophageal cancer is made by endoscopy with biopsy. Optimal staging is with endoscopic ultrasonography for depth of invasion and regional nodes and CT scanning for distant metastases. Neoadjuvant chemotherapy and radiation therapy followed by surgery is widely practiced, but survival benefits remain to be proven. Palliation of dysphagia may be achieved with surgery, radiation therapy, or endoscopic means, with the latter having fewer complications.

Hepatitis C virus (HCV) infection is currently the most common cause of fibrosing liver disease and represents a major clinical challenge. In patients with HCV infection, inflammation and injury lead to fibrosis and cirrhosis in a significant proportion of patients; cirrhosis in turn has multiple clinical sequelae. Therefore, understanding the pathological basis of fibrogenesis in hepatitis C infection is critical. This review will highlight fundamental issues underlying the fibrogenic response to injury and in addition will focus on potential points of intervention.

Hepatitis C virus (HCV) infection is the most common indication for liver transplantation in North America and Europe. While hepatitis C recurrence is common after transplantation, 5-year graft and patient survival in HCV-infected patients are similar to those of patients transplanted for other chronic liver diseases. With longer periods of follow-up, the proportion of patients with fibrosis or cirrhosis increases and graft loss does occur because of recurrent disease. Both viral and host factors have been linked to risk of disease progression. Specific therapies to eradicate infection or slow down disease progression are under study, and the most promising results to date have been obtained with combined interferon and ribavirin.

Post-treatment relapse remains a major issue in the long-term management of chronic hepatitis C. Many studies have been conducted to identify the ideal therapy that would increase the cost-effectiveness of retreatment in the individual patient. Although the conclusions of two consensus conferences for the retreatment of relapse of chronic hepatitis C have been published recently, several important issues still remain unanswered. We reviewed the available data by an evidence-based approach and conclude the following: (1) patients should be retreated with a combination of interferon (IFN) and ribavirin for 6 months if there are no contraindications to ribavirin; (2) the excellent tolerability and the lesser expense of retreatment with IFN monotherapy makes it a low-cost option for patients who have transiently cleared HCV-RNA during the first IFN course, and a primary indication for those who are contraindications to ribavirin or are likely to experience adverse events under ribavirin; (3) relapsers retreated with monotherapy must receive a high dose of IFN; and (4) patients with cirrhosis should not be retreated with IFN alone. More data, particularly on the long-term course of patients retreated with combination therapy, are needed before setting guidelines for retreatment of relapsers.

Since the National Institutes of Health (NIH) Consensus Conference in 1997, our understanding of the natural history of hepatitis C (HCV) infection and our ability to treat patients has improved. Thus, a large number of clinical studies, confounding terminology, and a growing dilemma in targeting particular populations for treatment who have HCV infection, will continue to be at the forefront of clinical research and treatment. In this report, we examine which HCV-infected populations of patients should be treated. Beginning with treatment guidelines from the NIH Consensus Conference, and a brief overview of the terminology used in the HCV literature, we subsequently review data regarding treatment outcomes based on HCV viral load, genotype, and various epidemiological factors. Similarly, more challenging treatment strategies are discussed for patients with HCV infection, including those with ongoing psychiatric disorders, patients who are coinfected with the human immunodeficiency virus and HCV, and those patients with normal serum transaminases. Finally, a review and guidelines about other HCV treatment dilemmas, including patients with chronic renal failure on hemodialysis, patients who have undergone renal transplantation, and treatment of patients acutely exposed to HCV are also addressed.

Although early data suggested that chronic hepatitis C virus infection carried little risk, studies with longer duration of infection have reported concerning results. Of patients with acute infection, approximately 80% will develop chronic infection. The greatest risk of morbidity comes with cirrhosis and the resulting increased risk of hepatocellular carcinoma. The true risk of progression to cirrhosis, however, has emerged as an area of controversy. Both host and viral factors seem to impact susceptibility to chronic infection, cirrhosis, and hepatocellular carcinoma. Hepatitis C virus has become the most common indication for liver transplantation, but the infection routinely recurs and may have a more aggressive course after transplantation. Given that current treatment options for hepatitis C virus infection are clearly not optimal, informed decisions regarding treatment require an in depth understanding of the natural history.

A by-product of increasing experience with patients infected with the hepatitis C virus is the awareness of a variety of extrahepatic syndromes that seem to be associated with HCV infection. Recent investigations into the relationship between the hepatitis C virus and human cells, particularly lymphocytes, have resulted in possible pathophysiological interactions that may begin to explain some of the extrahepatic manifestations of hepatitis C virus infection. In this review, we will discuss some of the potential interactions from both pathophysiological and clinical viewpoints.

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is currently the procedure of choice for ulcerative colitis patients who require colectomy. Despite its wide acceptance, a variety of long-term complications of the procedure exist that can be severe and even lead to pouch excision. Pouchitis occurs in up to one half of patients after IPAA, but is usually well controlled with medical therapy. A small percentage of patients develop chronic persistent pouchitis, which often requires long-term medical therapy and may result in pouch failure. Fistulas and strictures can also complicate the pouch procedure. In general, patients with Crohn's disease are not usually offered IPAA, because recurrence of disease, fistulas, abscesses, and strictures may lead to a higher incidence of pouch failure. Some ulcerative colitis patients develop complications after IPAA and are subsequently diagnosed with Crohn's disease. These patients may develop refractory fistulas, strictures, and extraintestinal manifestations of inflammatory bowel disease. Neoplastic transformation of the pelvic pouch has also been reported, particularly in patients with chronic pouchitis. Thorough follow-up and endoscopic surveillance with biopsies of the ileal pouch are therefore recommended.

The surgical management of Crohn's disease has always been a challenging issue for physicians because of concerns of the historical need for repeated surgeries over time, the physiological limitations of a shortened small bowel, and the transmural, fistulizing, and/or skip-lesion nature of the disease. Patients are fearful of the potentially disfiguring results, especially the need for a permanent ostomy. The challenge has been to develop surgical approaches that are bowel sparing and/or minimally invasive. Stricutureplasty has been used with relatively good results as a bowel-sparing procedure for patients with small-bowel Crohn's disease, potentially sparing patients of a short-bowel syndrome. Laparoscopic approaches to Crohn's disease have thus far been mostly limited to ileocecal resections in selected patients, but as more expertise is developed, will hopefully be extended to other surgical procedures in patients with Crohn's disease in the future. Patient criteria, success rates, complications, and economic implications are discussed for each procedure.