Temozolomide as salvage treatment in primary brain lymphomas

Methotrexate (MTX)-based chemotherapy extends survival in patients with primary brain lymphomas, but it is not clear whether multiagent chemotherapy is superior to MTX alone. Treatment options for patients with recurrent primary brain lymphoma are limited; there is no standard second-line chemotherapy. New chemotherapeutic agents with clear activity in brain lymphoma are needed for treatment of recurrent disease. We report the results of a phase II trial assessing activity of the alkylating agent temozolomide in immunocompetent patients with recurrent primary brain lymphomas, previously treated with high-dose MTX-containing chemotherapy and/or radiotherapy. A median of two courses (range 1-12) of temozolomide 150 mg m-2 day-1, for 5 days every 4 weeks was administered to 36 patients yielding nine complete and two partial responses (response rate: 31%; 95% confidence interval 16-46%). One-year survival was 31% (95% confidence interval 16-46%). Toxicity was negligible. We conclude that temozolomide is active in recurrent primary brain lymphomas and should further be evaluated in this disease, perhaps in combination with MTX as initial treatment.     

Brain edema and inflammatory activation in bile duct ligated rats with diet-induced hyperammonemia: A model of hepatic encephalopathy in cirrhosis

Studies of the pathogenesis of hepatic encephalopathy are hampered by the lack of a satisfactory animal model. We examined the neurological features of rats after bile duct ligation fed a hyperammonemic diet (BDL+HD). Six groups were studied: sham, sham pair-fed, hyperammonemic, bile duct ligation (BDL), BDL pair fed, and BDL+HD. The BDL+HD rats were made hyperammonemic via an ammonia-containing diet that began 2 weeks after operation. One week later, the animals were sacrificed. BDL+HD rats displayed an increased level of cerebral ammonia and neuroanatomical characteristics of hepatic encephalopathy (HE), including the presence of type II Alzheimer astrocytes. Both BDL and BDL+HD rats showed activation of the inflammatory system. BDL+HD rats showed an increased amount of brain glutamine, a decreased amount of brain myo-inositol, and a significant increase in the level of brain water. In coordination tests, BDL+HD rats showed severe impairment of motor activity and performance as opposed to BDL rats, whose results seemed only mildly affected. In conclusion, the BDL+HD rats displayed similar neuroanatomical and neurochemical characteristics to human HE in liver cirrhosis. Brain edema and inflammatory activation can be detected under these circumstances.     

Prospective clinical and manometric study of fistulotomy with primary sphincter reconstruction in the management of recurrent complex fistula-in-ano

Background and aims The aim of this study was to assess the results of fistulotomy with sphincter reconstruction in the management of recurrent complex fistula-in-ano in terms of recurrence and continence.Patients and methods Prospective study of 16 patients undergoing fistulotomy with sphincter reconstruction for recurrent complex fistula-in-ano was done. Preoperative and postoperative evaluation included physical examination, anal ultrasonography and anal manometry, with a 40-month follow-up. The Wexner Continence Grading Scale (0–20) was used to assess faecal continence.Results Fistulas were classified as high transsphincteric in 13 patients (81.3%), suprasphincteric in 2 (12.5%) and extrasphincteric in 1 patient (6.2%). Four patients (25%) had recurred twice or more. Eight patients (50%) complained of varying degrees of prior faecal incontinence. Their mean score decreased from 8.5 to 1.875 after surgery, and all the patients improved except for one whose score remained the same. On anal manometry, the differences between continent and incontinent patients before surgery [maximum resting pressure (MRP) 86.3 vs 57.6 mmHg, maximum squeeze pressure (MSP) 196.5 vs 138.6 mmHg] decreased after surgery (MRP 81.9 vs 63.7 mmHg, MSP 179.8 vs 159.3 mmHg). In fully continent patients, both the clinical score and manometric values were quite similar after surgery. Two fully continent patients (25%) developed occasional flatus incontinence and soiling, scoring two and three points, respectively. One patient recurred (6.25%) 6 months after surgery.Conclusion Fistulotomy with sphincter reconstruction seems to be an effective resource in the management of recurrent complex fistula-in-ano. It improves both anal continence and manometric values in incontinent patients without compromising them in fully continent ones.     

Low-dose thalidomide with pegylated liposomal doxorubicin and high-dose dexamethasone for relapsed/refractory multiple myeloma: a prospective, multicenter, phase II study

The aim of this prospective, multicenter, phase II study was to investigate the combination of pegylated liposomal doxorubicin (Caelyx) 40 mg/m2 on day 1 every 28 days, dexamethasone 40 mg p.o. on days 1-4 and 9-12 and thalidomide 100 mg daily in 50 patients with advanced multiple myeloma. Twenty-six percent of patients achieved a complete response, 6% a near complete response, 6% a very good partial response, 38% a partial response, 16% a minor response and 8% progressed, for an overall response rate of 92%. The median event-free survival was 17 months and the median overall survival was not reached. Grade 3 non-hematologic toxicity occurred in 12% of patients, thromboembolic disease in 12% and severe infection in 16%. The combination of pegylated liposomal doxorubicin, dexamethasone an thalidomide is safe and very effective in advanced multiple myeloma.     

Correction to: Management of mixed cryoglobulinemia with rituximab: evidence and consensus-based recommendations from the Italian Study Group of Cryoglobulinemia (GISC)

Clinical Rheumatology -