Archive for June, 2008
Posted by Alex
About 10 percent of patients with myeloma will have an indolent course demonstrating only very slow progression of disease over many years. Such patients only require antitumor therapy when the serum myeloma protein level rises above 50 g/L (5 g/dL) or progressive bone lesions develop. Patients with solitary bone plasmacytomas and extramedullary plasmacytomas may be expected to enjoy prolonged disease-free survival after local radiation therapy to a dose of around 40 Gy. There is a low incidence of occult marrow involvement in patients with solitary bone plasmacytoma. Such patients are usually detected because their serum M component falls slowly or disappears initially only to return after a few months. These patients respond well to systemic chemotherapy.
The vast majority of patients with myeloma require therapeutic intervention. In general, such therapy is of two sorts: systemic chemotherapy to control the progression of myeloma, and symptomatic supportive care to prevent serious morbidity from the complications of the disease. All patients with stage II or III disease and stage I patients exhibiting Bence Jones proteinuria, progressive lytic bone lesions, vertebral compression fractures, recurrent infections, or rising serum M component should be treated with systemic combination chemotherapy. Therapy can prolong and improve the quality of life for myeloma patients.
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Posted by Alex
Multiple myeloma is a malignant proliferation of plasma cells. The tumor, its products, and the host response to it result in a number of organ dysfunctions and symptoms of bone pain or fracture, renal failure, susceptibility to infection, anemia, hypercalcemia, and occasionally clotting abnormalities, neurologic symptoms, and vascular manifestations of hyperviscosity.
Etiology The cause of myeloma is not known. Myeloma occurred with increased frequency in those exposed to the radiation of nuclear warheads in World War II after a 20-year latency. In contrast to most other B cell tumors, consistent chromosomal alterations have not been found in patients with myeloma, though cytogenetic abnormalities are noted in a substantial fraction of cases. Overexpression of myc or ras genes has been noted in some cases. Mutations in p53 and Rb-1 have also been described, but no common molecular pathogenesis has yet emerged. The murine plasmacytoma models suggest that the induction of plasmacytomas (e.g., with mineral oil injection) may require exposure to foreign antigens as well as a cellular event. Thus chronic antigenic stimulation may play a role in the transformation of a particular B cell clone. This is supported by evidence that M proteins from different persons sometimes share idiotypes. There is also some evidence for a genetic predisposition to myeloma in humans. Myeloma has been seen more commonly than expected among farmers, wood workers, leather workers, and those exposed to petroleum products. The neoplastic event in myeloma may involve cells earlier in B cell differentiation than the plasma cell. Circulating B cells bearing surface immunoglobulin that share the idiotype of the M component are present in myeloma patients. It is possible that the malignant clone escapes normal control mechanisms at a pre-plasma cell stage of differentiation and the chronic exposure to a particular antigenic stimulus drives the cell to terminal differentiation. Interleukin (IL) 6 may play a role in driving myeloma cell proliferation; a large fraction of myeloma cells exposed to IL-6 in vitro respond by proliferating. It remains difficult to distinguish benign from malignant plasma cells on the basis of morphologic criteria in all but a few cases.
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Posted by Alex
1. Kornbluth AA, Salomon P, Sacks HS, et al. Meta-analysis of the effectiveness of current drug therapy of ulcerative colitis. J Clin Gastroenterol 1993;16:215-8.
2. Meyers S, Janowitz HD. The “Natural History” of ulcerative colitis: An analysis of the placebo response. Am J Gastroenterol 1989;11:33-7.
3. Calkins BM. Inflammatory bowel diseases. In: Everhart JE, ed. Digestive Diseases in the United States. Epidemiology and Impact. National Institute of Health, 1994.
4. Waye JD. Endoscopy in inflammatory bowel disease. In: Kirsner JD, Shorter RG, ed. Inflammatory bowel disease. Philadelphia: Lea and Fabiger, 1988, pp 353-76.
5. Surawicz SM, Belic L. Rectal biopsy helps to distinguish acute self-limited colitis from idiopathic inflammatory bowel disease. Gastroenterology 1984;86:104-13.
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Posted by Alex
After 8-10 years of colitis, annual surveillance colonoscopy with multiple biopsies at regular intervals should be performed. The finding of definite dysplasia of any grade, confirmed by expert pathologists’ review, is an indication for colectomy.
Patients with UC are at increased risk for colorectal cancer; the degree of risk is related to duration of disease and anatomic extent of colitis [110] [111] . After 10 yr of universal disease, the cancer risk is in the range of 0.5-1%/yr [110] [111] [112] [113] . Even patients with left-sided colitis reach similar levels of cumulative cancer risk after 3-4 decades of disease [111] [114] [115] ; patients with proctosigmoiditis are not at increased cancer risk. Although some data suggest a later onset of cancer risk in left-sided than in more extensive colitis [110] , this evidence is not sufficiently strong to justify different guidelines for surveillance in the two groups. Compared with noncolitis-associated colorectal cancer, colitis-associated cancers are more often multiple, broadly infiltrating, anaplastic, and uniformly distributed throughout the colon, and seem to arise from flat mucosa instead of following the usual adenoma-cancer sequence [114] [116] . Furthermore, colitis-associated colorectal cancer often occurs in a much younger patient population than does colorectal cancer in the general population [111] [113] .
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Posted by Alex
Absolute indications for surgery are exsanguinating hemorrhage, perforation, and documented or strongly suspected carcinoma. Other indications for surgery are severe colitis with or without toxic megacolon unresponsive to conventional maximal medical therapy, and the patient with less severe, but medically intractable symptoms or intolerable steroid side effects.
There are no prospective randomized trials comparing medical treatment with surgery for any indication in ulcerative colitis, but three situations are absolute indications for surgery because continued medical therapy is doomed to failure and potentially fatal: exsanguinating hemorrhage, frank perforation, and documented or strongly suspected carcinoma, i.e., high grade dysplasia or low grade dysplasia in a mass lesion. Generic Ampicillin 500mg
Massive hemorrhage in ulcerative colitis is due to diffuse mucosal ulceration. If the hemorrhage is exsanguinating or even persisting despite maximal medical therapy (see above), it is an indication for emergency surgery. If the patient’s condition permits, total proctocolectomy may be the most reliable procedure because a small group (approximately 12%) of patients may have continued hemorrhage from the retained rectal segment if only a subtotal colectomy is performed [96] [97] . On the other hand, subtotal colectomy with preservation of the rectum for a future restorative procedure is an acceptable choice, so long as the small risks of further hemorrhage are appreciated and appropriately monitored.
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