The role of anthracyclines in combination chemotherapy for the treatment of follicular lymphoma: retrospective study of the Intergruppo Italiano Linfomi on 761 cases

In order to elucidate the role of anthracycline based combination chemotherapy regimens for the treatment of follicular lymphoma we conducted a retrospective study on a large series of patients with a histologically confirmed diagnosis of follicular lymphoma. The Italian lymphoma intergroup (ILI) promoted a retrospective study of patients with follicular lymphoma treated in cooperative trials between 1985 and 1996. Six hundred and thirty three cases were treated with an anthracycline-containing regimen and 128 patients were treated without anthracyclines. The two groups were prognostically comparable; in particular, no difference was observed according to both IPI and ILI prognostic index. Results showed a complete remission (CR) rate for patients treated with anthracyclines was 69.2% and overall response rate was 92.5%. After a median follow-up of 51 months (54 months for patients still alive), the 5- and 10-year overall survival (OS) rates were 80 and 66%, respectively. Disease-free survival (DFS) and failure-free survival (FFS) rates at 5 years were 61 and 49%, respectively. In the group of patients treated with combination chemotherapy not including anthracyclines, the CR rate was 67.5% and the overall response rate was 85.4%. A longer OS (80% at 5 years) was observed in patients treated with anthracyclines compared to 67% OS rate in patients treated without anthracyclines (p = 0.0004). FFS was significantly longer in patients treated with anthracyclines (49 vs. 34% p = 0.006). Patients treated with anthracyclines with low or intermediate risk according to ILI prognostic index showed a significantly longer OS (p = 0.0001 andp = 0.0009, respectively); those in the high-risk group showed a trend for a longer survival. In conclusion, this retrospective study shows that patients with follicular lymphoma treated with an anthracycline containing regimen had a better outcome compared to patients treated with other combination regimens non including anthracyclines in terms of CRs, OS and FFS. On the basis of these results anthracycline-containing regimens (ACR) should be considered as the standard treatment of patients with advanced follicular lymphoma.     

The role of the ubiquitination-proteasome pathway in breast cancer: use of mouse models for analyzing ubiquitination processes

Turnover of several regulatory proteins results from targeted destruction via ubiquitination and subsequent degradation through the proteosome. The timely and irreversible degradation of critical regulators is essential for normal cellular function. The precise biochemical mechanisms that are involved in protein turnover by ubiquitin-mediated degradation have been elucidated using in vitro assays and cell culture systems. However, pathways that lead to ubiquitination of critical regulatory proteins in vivo are more complex, and have both temporal and tissue-specific differences. In vivo models will allow identification of substrates and enzymes of the ubiquitin-proteosome pathway that play important roles in selected tissues and diseases. In addition, assessment of the therapeutic efficacy of drugs designed to inhibit or enhance protein turnover by ubiquitination requires in vivo models. In the present review we describe selected examples of transgenic and knockout models of proteins that are known either to be regulated by ubiquitin-mediated degradation or to have a catalytic function in this process, and to play an important role in breast cancer. We outline the functions of these proteins in vivo and focus on knowledge gained in the comparison of in vivo behavior predicted from cell-free in vitro data or from experiments conducted in cell culture systems.     

Influence of stimulus color on the control of reaching-grasping movements

This kinematic study aimed to determine whether color is a stimulus property involved in the control of reaching-grasping movements. Subjects reached and grasped a target-object, located either on the right or on the left of the subject's midline. A distractor, placed along the subject's midline, could be randomly presented. The colors, i.e., both chromaticity (red and green stimuli were presented) and lightness, of the target and distractor were varied in experiment 1. Only stimulus lightness and only stimulus chromaticity were varied in experiments 2 and 3, respectively. In experiment 4 subjects matched with their thumb and index finger the size of the target-stimuli presented in experiment 1. Chromaticity (experiments 1 and 3) of the target and distractor influenced grasp, but not reach. Maximal finger aperture was larger during grasping the red than the green target. Data collected in the matching task (experiment 4) confirmed a trend to overestimate the red target and to underestimate the green one. During grasp, hand shaping was influenced by distractor chromaticity when it was different from target chromaticity. Distractor lightness affected reach, but not grasp (experiments 1 and 2). Reach was slower when the distractor was lighter and arm trajectory veered away from it. The results of the present study suggest that color, that is the ensemble of chromaticity and lightness, is a stimulus property involved in the control of reaching-grasping. The different effects of target color on reach and grasp support the notion that intrinsic object properties, such as color, affect grasp more than reach. In addition, the different effects of distractor chromaticity and lightness on reach and grasp confirm that target-objects are visually extracted from surrounding cues by means of different processes, according to the required motor response.     

Preinduction cervical ripening techniques compared

OBJECTIVE: To assess the clinical efficacy of pharmacologic, mechanical and combination techniques of cervical ripening. STUDY DESIGN: From March 1997 to August 1998, all cervical-ripening patients at Lehigh Valley Hospital were randomly assigned to three groups: intravaginal misoprostol, intracervical Foley catheter, or combination prostaglandin E2 (PGE2) gel and Foley catheter. Inclusion criteria included Bishop score < or = 5 and no contraindication to labor. The remaining delivery process was actively managed according to established guidelines. Multiple variables in perinatal outcome were analyzed, with the cesarean section rate and time from ripening to delivery as the main outcome variables. RESULTS: Of the 205 patients, 65 were randomized to the misoprostol group, 71 to the Foley group and 69 to the catheter-and-gel group. There were no differences between groups in delivery indications, maternal demographics, ultrasound findings, labor interventions, intrapartum times, mode of delivery, postpartum complications or neonatal outcomes. The misoprostol group demonstrated a higher rate of uterine tachysystole and required oxytocin less when compared to the two catheter groups. CONCLUSION: The higher rate of uterine tachysystole with misoprostol did not increase the cesarean section rate. The higher rate of oxytocin required by the two catheter groups did not increase the delivery time intervals. There appears to be no benefit to adding intracervical or intravaginal PGE2 gel to the intracervical Foley balloon. The misoprostol and catheter ripening techniques have similar safety and efficacy.     

Syndrome of cholesterol crystal embolism: clinical case

Cholesterol crystal embolization syndrome is a multiorgan disease that frequently occurs as a complication of invasive cardiovascular procedures and of thrombolytic or anticoagulant therapy. The symptoms are due to the displacement of atheromatous material dislodged from unstable or injured, by mechanical manipulation, plaque to arteriolar vessels. The real incidence of cholesterol embolization is not known. Often the diagnosis is missed because of the time between intervention and clinical findings and because the organs involved can be many and various. The most common clinical manifestations are acute renal failure and hypereosinophilia. The prognosis is poor and the mortality high because of the progression of renal failure. In this case report we present the clinical history of a 62-year-old male patient with a history of cigarette smoking and hypertension who was submitted to emergency surgery following the acute dissection of a type A aortic aneurysm. About 2 weeks after surgical intervention the patient developed a multiorgan disorder (gastroenteric, neuromuscular and renal involvement) associated with hypereosinophilia and with increased levels of the markers of inflammation. The symptoms were transient and probably due to embolization of cholesterol crystals; no specific therapy was administered. On the other hand, no therapeutic regimen has been codified to date. The best clinical approach is prophylactic, that means identifying those patients who are at high risk for an invasive vascular procedure.     

Radiofrequency-assisted liver resection

Radiofrequency (RF)-assisted thermal ablation has been used with increasing frequency for unresectable hepatic tumors. This new approach employs RF energy to coagulate the liver at the hepatic resection line after which hepatic resection is performed with the use of a common scalpel. This procedure was used in three patients with hepatocellular carcinoma and in five patients with colorectal metastasis to the liver. These eight patients underwent a total of two left bisegmentectomies, three segmentectomies, and seven wedge resections. Mean operative time was 220 minutes. A mean of 78 sessions of RF-assisted ablation were required for these resections. Mean blood loss was 46 ml; no device other than RF ablation was required to obtain hemostasis. None of the patients needed a blood transfusion. Preoperative hemoglobin was 12.8 gm/dl and postoperative hemoglobin was 11.3 gm/dl. There were no perioperative deaths. Postoperative complications occurred in two patients: a liver abscess in one and heart failure in the other. The mean hospital stay was 9.4 days. This new approach, integrated with other techniques, reduces blood loss and coagulates the margins of resection during liver surgery. This new technique has two limitations: (1) it cannot be applied near main portal pedicles, and (2) it requires a long operative time. The best indication for this technique is when segmentectomy is required in patients with cirrhosis. Its role in major hepatic resections has yet to be determined. Further progress in the development of thermal ablation techniques and experience gained during the learning curve should help reduce the operative time, thereby improving the safety and efficacy of this procedure. Presented at the Third International Meeting, "Hepatocellular Carcinoma: Eastern and Western Experience," Lodi, Italy, November 21–22, 2002.