Prospective evaluation of interferon-alpha in treatment of chronic active Crohn's disease.

Several case reports suggested good effects of interferon-alpha in patients with Crohn's disease. In addition, a decreased production of interferon-alpha in Crohn's disease has been shown in vitro. Treatment with interferon-alpha may activate intestinal natural killer cells and down-regulate the overproduction of inflammatory cytokines like interleukin-6 in Crohn's disease. To evaluate the clinical efficacy of interferon-alpha, we treated 12 patients with a chronic active course of Crohn's disease with recombinant human interferon-alpha prospectively for 24 weeks. Prednisolone was continuously tapered and discontinued at week 12. The end point of the study was the prevention of worsening of clinical symptoms defined with the Crohn's disease activity index and was monitored by acute-phase proteins, interleukin-6 serum concentrations, and endoscopy. The biochemical activity of interferon-alpha was measured by 2',5'-oligo adenylate serum levels. The end point of the study was reached in four patients (33%). In these patients the final Crohn's disease activity index was above 150, which means that they did not achieve clinical remission. All other patients (66%) did not respond to interferon-alpha and had to be withdrawn prematurely. Interferon-alpha did not show any beneficial effect on interleukin-6 or acute-phase protein concentrations and on endoscopic activity. The 2',5'-oligo adenylate levels continuously increased during interferon therapy. Considerable side effects were noted. These results fail to demonstrate a therapeutic role of interferon-alpha in chronic active Crohn's disease.

Prognostic factors in adenocarcinoma of the cardia.

BACKGROUND: The optimal extent of resection for adenocarcinomas of the gastroesophageal junction is controversial. This study was conducted to examine whether the extent of resection is an independent prognostic factor in cardia cancer. METHODS: The records and survival data of 125 patients who underwent resection for cancer of the cardia were retrospectively analyzed. Multiple regression was used to evaluate prognostic factors in patients who underwent proximal gastric resection (PR) or total gastrectomy (TG) for cancer of the cardia. RESULTS: Seventy-five patients underwent PR and 50 TG. The 5-year survival was 40% for tumors confined to the esophageal wall (T1, T2), and 13% in more advanced cases (T1, T2; P = 0.0001). Twenty-two percent of the patients with tumor-free margins, 10% of those with microscopic residual tumor, and none with macroscopic residual tumor survived longer than 5 years (P = 0.0001 for any residual tumor versus no residual tumor). Lymph node involvement (P = 0.002) and stage (P = 0.0001) were also significant in the univariate analysis. Five-year survival was 18% after TG, and 17% after PR (P = NS). CONCLUSION: Multiple regression identified residual tumor and penetration depth as independent predictors of survival (P = 0.0002, and P = 0.0001, respectively). After correction for these factors, none of the following variables were of additional significance: extent of resection (TG versus PR), lymph node involvement, age, or Lauren's classification. In 19 of 20 cases with microscopic incomplete resection, it was the oral margin that was positive. We conclude that the extent of resection (TG versus PR) does not influence survival in adenocarcinoma of the gastroesophageal junction.

In vitro NMR investigation of controlled single and repeated isoflurane anesthesia.

Immobilization of laboratory animals is a basic requirement for experimental in vivo NMR measurements. The effect of single and repeated isoflurane anesthesia on proton NMR relaxation times T1 and T2 in rat liver was studied. Furthermore, physiological monitoring was performed to evaluate the influence of isoflurane anesthesia (up to 2 hr) on biological parameters. Neither single nor repeated isoflurane application over the observed time produce relevant alterations of physiological parameters or relaxation times, compared with untreated control groups. Therefore, we conclude that isoflurane anesthesia is appropriate for in vivo NMR investigations, especially of the liver.

[Risk factors for local recurrence of rectal carcinoma]. / Risikofaktoren für Lokalrezidivierung beim Rektumkarzinom.

The impact of distal resection margins and the mode of operation on pelvic recurrence rate was assessed in 331 cases following abdomino-perineal resection (APR; n = 134), and anterior resection (AR; n = 197) for rectal cancer. Local recurrence was observed in 55 cases (16.6%) after a median interval of 16 months. Only 20 of 212 patients (9.4%) without positive lymph nodes developed a local recurrence, but 35 of 119 (29.4%) with nodal involvement. The recurrence rate was 33% (10/30) in cases with local spread to adjacent structures (T4), and 15% in cases with less extensive penetration. Of 59 poorly differentiated cancers 15 developed pelvic failure (25%), as opposed to 40 of 272 (14.7%) well or moderately differentiated tumours. 17.7% developed local recurrence after AR, and 14.9% after APR. The recurrence rate following AR was 30% in 33 cases with resection margins less than or equal to 10 mm and 17.4% in 115 cases with margins from 11 to 40 mm, and 10% in 49 cases with wider margins. Cox's multiple proportional hazards regression revealed that nodal involvement (p = 0.0003), local invasion (p = 0.0055), poor differentiation (p = 0.066), and AR vs. APR (p = 0.099) were independent risk factors for pelvic failure. For the AR cases the factors were nodal involvement (p less than 0.0001), local invasion (p = 0.0043), and a resection margin less than or equal to 25 mm on the fixed specimen (p = 0.0039). For patients with negative lymph nodes local invasion was the only independent risk factor, whereas the variables "anterior resection" and narrow resection margin were significant only in node positive cases.(ABSTRACT TRUNCATED AT 250 WORDS)