Treatment of chronic hepatitis C: Improved combination therapy

There has been considerable progress in the treatment of chronic hepatitis C since the first report that interferon (IFN) monotherapy was effective in 1989. Early results were meager, with sustained loss of hepatitis C virus from blood in fewer than 10% of cases. The combination of IFN with the oral nucleoside analogue ribavirin was a major breakthrough in clinical hepatology; it led to dramatic increases in treatment responses, with 30% to 40% of patients clearing virus. Pegylated IFNs that have prolonged activity and can be dosed once a week have now replaced standard IFNs. The combination of pegylated IFN with ribavirin is the new standard of care; it causes sustained loss of virus in more than half of treated patients. Treatment responses continue to be highly dependent on viral genotype. Patients with genotype 1, the most common type in the United States, have a sustained clearance rate of 42% to 46%, whereas those with genotype 2 or 3 have a response rate approaching 80%.     

Ninety-Six Five-Year Survivors After Liver Resection for Metastatic Colorectal Cancer

Background: Studies have consistently confirmed the benefit of liver resection for metastatic colorectal cancer. Few reports, however, have a long enough followup or sufficient 5-year survivors to study the clinical course of patients beyond 5 years.

Study Design: From July 1985 through December 1991, 456 patients underwent liver resection for colorectal metastases. Ninety-six actual 5-year survivors (21%) were identified and their clinical course retrospectively reviewed.

Results: Five-year survivors (n = 96) were more likely to have a Duke’s B primary colorectal carcinoma, fewer than four metastatic lesions, unilobar disease, and a negative histologic margin when compared with patients not surviving 5 years (n = 298). Forty-four (46%) of the 96 five-year survivors had a recurrence after hepatectomy. Of these 44, 19 (43%) were rendered disease free after further treatment. Overall, 71 of the 96 five-year survivors were free of disease at last followup. The actuarial 10-year survival of this group was 78%.

Conclusions: Patients that are disease free 5 years after liver resection are likely to have been cured by liver resection. Patients should be aggressively followed for recurrence because of the potential for further treatment and longterm survival.     

Cytokines as an adjuvant to tumor vaccines: Efficacy of local methods of delivery

Background: We examined alternative methods of delivering cytokines as an adjunct for priming lymph node (LN) cells draining sites of vaccine inoculation for the purpose of generating immune cells for adoptive immunotherapy. Methods: Using syngeneic murine tumors we examined the ability of IL-2, IL-4, or GM-CSF delivered locally to a site of tumor inoculum to induce antitumor reactive draining LN cells. Mice were inoculated subcutaneously with tumor cells transduced to secrete cytokine; tumor cells admixed with fibroblasts transduced to secrete cytokine; or intralesional inoculation of cytokine in established tumor to induce sensitized LN cells capable of mediating tumor regression in adoptive transfer. Results: Both IL-4 and GM-CSF cytokines were effective in enhancing the antitumor reactivity of vaccine-primed LN cells compared to IL-2, which was ineffective. The local delivery of GM-CSF by autocrine or paracrine secretion of genetically engineered cells, as well as direct intratumoral delivery was capable of upregulating LN sensitization compared to systemic administration, which did not. Conclusions: The local delivery of GM-CSF as an adjuvant for tumor vaccination can be accomplished by various methods, including direct injection, which avoids the need for gene transfer.     

Complement Killing of Yersinia enterocolitica and Retention of the Bacteria by Leucocyte Removal Filters

We report studies on the complement sensitivity of four strains of Yersinia enterocolitica , serotypes O:3, O:9, O:5,27, and O:20, isolated from blood units involved in transfusion fatalities. Complement in fresh CPD plasma killed Y. enterocolitica within 4 h at 22°C in 100% of the experiments. The bactericidal action was serotype and complement activation pathway dependent. Both classic and alternate pathways seemed to be active, but the latter to a lesser degree. When the classic pathway was blocked by chelation of Ca²⁺ no complete killing was obtained. Complement did not enhance or condition Yersinia for leucocyte filter retention. Direct removal of Yersinia by filtration was also related to serotype; all strains were reduced by filtration in heat-inactivated plasma, and all except serotype O:5,27 were reduced in Ca²⁺ -chelated plasma. Our findings may explain why plasma products and platelet concentrates are rarely involved in Yersinia sepsis related to transfusion.     

Expectant management of deep cerebral venous thrombosis with intraventricular hemorrhage

Limited randomized clinical trial data favor the use of anticoagulation in patients with cerebral venous thrombosis. We present a patient with deep cerebral venous thrombosis in whom anticoagulation was withheld because of coexistent intraventricular hemorrhage. She had a benign clinical course without anticoagulation, suggesting that close observation may be a management option in these patients.     

Endoscopic sphincterotomy for common bile duct stones: Impact of recent technical advances

Technical improvements, such as mechanical lithotripsy, stenting or nasobiliary drainage, and wire-guided cannulation, have reduced the risk of complications in endoscopic sphincterotomy. To determine the extent of this reduction in risk, we assessed the medical records of 1352 patients with common bile duct stones in whom the procedure was conducted. Complications examined were: acute cholangitis and pancreatitis. Stone clearance was achieved in 1256 patients (92.8%), with an overall morbidity rate of 7.7% and a mortality rate of 0.15%. One hundred and forty-two patients had stones with a diameter greater than 20mm; 97 of these patients did not undergo lithotripsy. Cholangitis occurred in 10 of these 97 patients (10.3%), whereas, in the 45 patients who underwent lithotripsy, there were no cases of cholangitis (P=0.02). Stone removal was not immediately accomplished or attempted in 396 patients. In 82 of these patients in whom a stent or a nasobiliary drain was placed in the common bile duct, the incidence of cholangitis was 1.2%, significantly less (P=0.045) than the incidence of 6.4% in the other 314 patients given no stenting or nasobiliary drain. To overcome difficult cannulation, precut sphincterotomy was conducted in 134 patients and wireguided sphincterotomy, a recently introduced procedure, was conducted in 55 patients. When the precutting technique was used, the incidence of acute pancreatitis was significantly higher (8/134; 6.0%) than that in the patients in whom the standard procedure was conducted, i.e., neither the precut technique nor wire-guided ES was used (23/1218; 1.9%) (P=0.008). There were no cases of pancreatitis in the 55 patients in whom wire-guided sphincterotomy was performed, although the difference was not statistically significant because of the small number of patients (P=0.06). Based on these findings, we conclude that improved technologies have led to a significant reduction of complications in endoscopic sphincterotomy.