Lenalidomide in the management of eosinophilic dermatosis of hematological malignancy

Eosinophilic dermatosis of hematological malignancy is a paraneoplastic skin eruption associated with chronic lymphocytic leukemia and other B‐cell malignancies. It clinically resembles an insect bite reaction and it can precede the symptoms of the hematological malignancy or be related to a more aggressive course. Different treatments have been proposed, but partial response and recurrence are frequent. Herein, we describe a case of eosinophilic dermatosis associated with mantle cell lymphoma with remission after lenalidomide therapy.     

Serum Interferon (IFN)-Neutralizing Antibodies and Bioactivities of IFNs in Patients with Severe Type II Essential Mixed Cryoglobulinemia

The efficacy of alpha interferon (IFN-α) in the treatment of severe type II essential mixed cryoglobulinemia (EMC) has been reported previously. In some patients, the development of neutralizing antibodies to recombinant IFN-α (rIFN-α) can affect the clinical response achieved with rIFN-α; a second treatment with natural IFN-α preparations may reinduce the clinical response. In the present study the ability of leukocyte IFN (LeIFN) to restore the response was investigated from a pharmacodynamic viewpoint. Specifically, the pharmacodynamic profiles of different IFN-α preparations were studied by measuring the serum neopterin levels and the levels of expression of protein MxA mRNA in in vivo peripheral blood mononuclear cells in two patients with EMC whose resistance to rIFN-α2a treatment increased concomitantly with the development of neutralizing antibodies. These markers were measured before injection and at 24 and 48 h after a single injection of rIFN-α2a, consensus IFN [(C)IFN], or LeIFN. No increase or only a slight increase in MxA mRNA levels was detectable after administration of rIFN-α2a or (C)IFN, whereas a significant increase (≥10-fold) in MxA mRNA expression was recorded following administration of LeIFN. The neutralizing antibodies to rIFN-α2a cross-react with (C)IFN. Sera from these patients neutralized most but not all of the subtypes present in the natural IFN-α (LeIFN) mixture, and no significant increase in neopterin levels was observed after these patients were switched to LeIFN treatment. In summary, the data demonstrate that the problem of neutralizing antibodies still exists and that LeIFN may induce an increase in the level of MxA mRNA expression but not an increase in neopterin levels in patients who are resistant to treatment with rIFN-α2a or (C)IFN.     

Clinical relevance of different sequencing of doxorubicin and cyclophosphamide, methotrexate, and Fluorouracil in operable breast cancer.

PURPOSE: To assess the clinical relevance of different sequences of doxorubicin (DOX) and cyclophosphamide, methotrexate, and fluorouracil (CMF) in patients with operable breast cancer at risk of disease relapse. PATIENTS AND METHODS: Two randomized trials were activated in the early 1980s. The first study, in patients with one to three involved nodes, was intended to assess the effectiveness of intravenous (i.v.) CMF given every 3 weeks for 12 courses versus eight courses of the same CMF regimen followed by four courses of full-dose DOX (CMF-->DOX). The second study, in patients with more than three involved nodes, compared four courses of full-dose DOX sequentially followed by eight courses of i.v. CMF (DOX-->CMF) versus alternating two courses of the same CMF regimen with one course of DOX (CMF/DOX) for a total of 12 courses. RESULTS: After a median observation of 210 months, no statistically significant difference was documented in the first study (relapse-free survival hazard rate [HR], 1.06; total survival HR, 1.03). In contrast, the delivery of DOX first, followed by CMF significantly reduced the risk of disease relapse (HR, 0.68; 95% CI, 0.54 to 0.87; P =.0017) and death (HR, 0.74; 95% CI, 0.57 to 0.95; P =.018) compared with the alternating regimen. CONCLUSION: Anthracycline-containing regimens can further reduce the odds of relapse and death compared with CMF. However, the findings observed in our trials emphasize that the relative merits of anthracycline adjuvant programs also can depend on the modality of administration and must be assessed in properly designed trials in which the magnitude of the benefits can be weighed against potential risks.     

Fecal Calprotectin Levels in Patients with Colonic Polyposis

Context The usefulness of stool calprotectin determination in diagnosis of inflammatory disease of the colon has been reported; information about its usefulness for patients with polyposis are scarce, however. Objective To evaluate the significance of stool calprotectin concentrations for patients affected by colonic polyposis. Patients Sixty-three consecutive patients (35 males, 28 females, mean age 60.3 years, range 39–78 years) were enrolled: 26 patients (41.3%) with polyps, 17 patients (27.0%) with asymptomatic diverticular disease, and 20 subjects (31.7%) with normal endoscopic appearance of the colon. Results Stool calprotectin concentrations were 17.4 ± 24.5 μg g⁻¹ for patients with colonic polyposis, significantly higher than concentrations for patients with diverticulosis (7.1 ± 5.7 μg g⁻¹; P = 0.026) or for patients with normal appearance of the colon (calprotectin 6.0 ± 5.8 μg g⁻¹; P = 0.003). For patients with a single polyp, stool calprotectin concentrations were similar to those for patients with multiple polyps. Calprotectin fecal concentrations for patients with sessile polyps and those with flat polyps were not significantly different. Calprotectin concentrations were not significantly related to the size of the polyps. Conclusion Our data show that colonic polyposis may cause an increase in stool calprotectin values and that these colonic lesions should be suspected when elevated stool calprotectin concentrations are found.     

Clinical,neurophysiological, and skin biopsy findings in peripheral neuropathy associated with hepatitis C virus-related cryoglobulinemia

Hepatitis C virus (HCV)-related cryoglobulinemia commonly causes disabling complications including peripheral neuropathy and neuropathic pain. In this prospective clinical, neurophysiological, and skin biopsy study we aimed at assessing clinical characteristics and risk factors of peripheral neuropathy and neuropathic pain in patients with HCV-related cryoglobulinemia. We enrolled 69 consecutive patients with HCV-related cryoglobulinemia. We diagnosed neuropathic pain with the DN4 (Neuropathic Pain Diagnostic) questionnaire, and rated the various neuropathic pains with the Neuropathic Pain Symptom Inventory (NPSI). All patients underwent a standard nerve conduction study to assess Aβ-fiber function, laser-evoked potentials to assess Aδ-fiber function, and skin biopsy to assess C-fiber terminals. Of the 69 patients studied, 47 had a peripheral neuropathy, and 29 had neuropathic pain. Patients with peripheral neuropathy were older than those without (P < 0.0001). While peripheral neuropathy was significantly associated with the duration of HCV infection (P < 0.01), it was unrelated to the duration of cryoglobulinemia and cryocrit (P > 0.5). The severity of peripheral neuropathy significantly correlated with the duration of HCV infection (P < 0.05). Laser-evoked potential amplitudes were significantly lower in patients with than in those without neuropathic pain (P < 0.05). Conversely, no difference was found in nerve conduction study and skin biopsy findings (P > 0.05). Our findings show that peripheral neuropathy is related to age and HCV infection, rather than to cryoglobulinemia, and neuropathic pain is associated with damage to nociceptive pathways as assessed with laser-evoked potentials; this might be useful for designing more effective clinical interventions for these common HCV related-cryoglobulinemia complications.     

New evidence of similarity between human and plant steroid metabolism: 5alpha-reductase activity in Solanum malacoxylon

The physiological role of steroid hormones in humans is well known, and the metabolic pathway and mechanisms of action are almost completely elucidated. The role of plant steroid hormones, brassinosteroids, is less known, but an increasing amount of data on brassinosteroid biosynthesis is showing unexpected similarities between human and plant steroid metabolic pathways. Here we focus our attention on the enzyme 5alpha-reductase (5alphaR) for which a plant ortholog of the mammalian system, DET2, was recently described in Arabidopsis thaliana. We demonstrate that campestenone, the natural substrate of DET2, is reduced to 5alpha-campestanone by both human 5alphaR isozymes but with different affinities. Solanum malacoxylon, which is a calcinogenic plant very active in the biosynthesis of vitamin D-like molecules and sterols, was used to study 5alphaR activity. Leaves and calli were chosen as examples of differentiated and undifferentiated tissues, respectively. Two separate 5alphaR activities were found in calli and leaves of Solanum using campestenone as substrate. The use of progesterone allowed the detection of both activities in calli. Support for the existence of two 5alphaR isozymes in S. malacoxylon was provided by the differential actions of inhibitors of the human 5alphaR in calli and leaves. The evidence for the presence of two isozymes in different plant tissues extends the analogies between plant and mammalian steroid metabolic pathways.     

Treatment of acute biliary pancreatitis: our experience

The results of endoscopic and surgical treatment in 21 patients affected by acute biliary pancreatitis are reported. All patients were managed according to the same protocol. Once the diagnosis was formulated (pain, serum amylase, ultrasonography, cholestasis and/or cholangitis) and the severity evaluated (Ranson's criteria, glucose and urea levels), the 21 patients underwent endoscopic retrograde cholangiopanctratography--within 24 hours in 8 patients (predicted severe disease) or within 72 hours in 13 patients (predicted mild disease). Endoscopic sphincterotomy was performed in 18 patients with stones in the common bile duct and was successful in 94.5% (17 patients: 3 patients underwent more than one session to confirm or achieve clearance of the duct). The morbidity rate associated with endoscopic sphincterotomy was 16% (3 patients: 2 haemorrhages, 1 perforation). There were no deaths. Cholecystectomy was performed in 16 patients within 2-9 weeks of the initial attack of acute biliary pancreatitis. There were 3 minor complications (respiratory, laparotomy, urinary infection), no major intraoperative or postoperative morbidity, and no mortality. Acute biliary pancreatitis is still associated with significant morbidity and mortality, but can be managed safely with combined medical, endoscopic and surgical treatment.     

Report of a case of Gardner's syndrome: clinical and epidemiologic considerations and review of the literature

Familial adenomatous polyposis is a hereditary clinical syndrome characterised by the presence of numerous adenomatous polyps of the colon and rectum and by lesions in other organs. The disease affects various different tissues and characteristically presents a variable biological and clinical behaviour. Colon polyps are precancerous lesions and the certainty of their malignant evolution within the 3rd-4th decades of life is now practically an established, extensively documented fact. Recently, new methods of genetic screening, prevention and early diagnosis and, as a result, more advanced treatment protocols have been introduced in clinical practice, thus offering young patients diagnosed as suffering from familial adenomatous polyposis better prospects and a better quality of life. The patient in our case came in for medical observation for abdominal pain experienced close to the scar of a previous appendectomy and for the presence of an abdominal tumefaction on the same side. Initially the patient underwent surgical resection of the growth that proved to be a desmoid tumour of the abdominal wall. The results of the pathology examination and the patients' long-term disease and family history led to a presumptive diagnosis of familial adenomatous polyposis, which was then confirmed by the appropriate instrumental examinations. Genetic tests on the patient's relatives yielded the same diagnosis in some of them. On the basis of our personal experience and a thorough review of the literature we can safely state that no medical treatment currently available is capable of reducing, let alone definitively eliminating colon polyps. To date, then, the therapeutic options most commonly adopted are colectomy with ileo-rectal anastomosis and total conservative proctocolectomy with an ano-ileal pouch anastomosis. These two types of surgical procedures yield different results in terms of functional capability and oncological radicality with their respective repercussions on the patient's quality of life. The choice of the most appropriate surgical procedure is made on the basis of a series of parameters such as age, site of the polyps, number of polyps, degree of cell atypia of the polyps, and patient willingness to undergo regular check-ups. The current tendency advocated by the various authors is to perform a total colectomy as soon as possible.     

Efficacy of low-dose rituximab for mixed cryoglobulinemia

Rituximab at 375 mg/m(2) x 4 is effective for refractory HCV-related mixed cryoglobulinemia. We conducted a pilot study to assess the efficacy of a lower dosage, 250 mg/m(2) x 2. Six consecutive patients with mixed cryoglobulinemia were treated. All patients had severe or life-threatening disease manifestations, including necrotizing skin ulcers, renal disease, hyperviscosity or intestinal vasculitis. Four of five evaluable patients (excluding one early death) had >80% decrease of cryocrit and remission of vasculitis at the end of a 22- to 55-week (median 40) follow-up. The non-responder failed to respond to additional rituximab treatment, suggesting intrinsic resistance rather than insufficient dosage as the cause of treatment failure. No sustained increase of HCV viremia after rituximab was observed. Rituximab at 250 mg/m(2) x 2 may be as effective as at 375 mg/m(2) x 4 for treating mixed cryoglobulinemia. Larger studies are required to assess the efficacy of low-dose rituximab.