Preoperative Chemoradiation for Extraperitoneal T3 Rectal Cancer: Acute Toxicity, Tumor Response, and Sphincter Preservation

Purpose: To evaluate whether or not an intermediate dose of preoperative external radiation therapy intensified by systemic chemotherapy could improve the tumor response, sphincter preservation, and tumor control.

Methods and Materials: Between March 1990 and December 1995, 83 consecutive patients with resectable extraperitoneal adenocarcinoma of the rectum were treated with preoperative chemoradiation: bolus i.v. mitomycin C (MMC), 10 mg/m², Day 1 plus 24-h continuous infusion i.v. 5-fluorouracil (5FU) 1000 mg/m², Days 1–4, and concurrent external beam radiotherapy (37.8 Gy). All but 2 patients had T3 disease. Surgery was performed 4–6 weeks after the end of chemoradiation.

Results: Total Grade 3–4 acute toxicity during chemoradiation was observed in 11 (13%) patients: hematological Grade 3 toxicity was recorded in 8 (10%) patients, and Grade 4 toxicity was recorded in 2 (2%) patients. Grade 3 diarrhea was seen in 2 (2%) patients. No patient had major skin or urological acute toxicity. Two patients had no surgery: 1 died before surgery from septic complications after Grade 4 hematological toxicity; 1 refused surgery and is still alive after 6 years. There was no postoperative mortality and the overall perioperative morbidity rate was 25%. The analysis of tumor response involved 81 patients. Overall, 9% [7] of 81 patients had a complete pathologic response. Comparing the stage at the diagnostic workup with the pathologic stage, tumor downstaging was observed in 46 (57%) patients. We had 7 (9%) pT0, 5 (6%) pT1, 33 (41%) pT2, and 36 (44%) pT3. Nodal status downstaging was detected in 46 patients (57%). No evidence of nodal involvement was observed in 59 patients (73%). The incidence of tumor response was affected significantly by the number of quarters of rectal circumference involved (p = 0.03) and, marginally, by the length of the tumor (p = 0.09). The distance between the lower pole of the tumor and the anorectal ring had no influence. Of the patients, 63 (78%) had a sphincter-saving surgical procedure. In 12 (44%) of 27 patients candidate for an APR, the sphincter was preserved, as it was in 19 (95%) of 20 probable candidates. Lengthening of the distance between the anorectal ring and the lower pole of the tumor > 20 mm was observed in 21 patients (26%). Of 63 patients, 4 (6%) had moderate soilage after the sphincter-saving procedure.

Conclusion: Preoperative combined modality therapy seems to afford some potential advantages in nonrandomized trials: patients are able to tolerate higher chemotherapy doses and they experience a lower acute toxicity. Tumor downstaging and resectability rates are high; sphincter preservation is feasible. Larger T3 tumors remained less influenced by this treatment; thus, taking into account the low toxicity rate recorded, a more aggressive schedule should be applied in these resectable tumors.     

Expression and activity of CYP2E1 in circulating lymphocytes are not altered in diabetic individuals

Cytochrome P4502E1 (CYP2E1) plays an important role in ROS production thus favouring accelerated membrane lipid peroxidation. This isoform is strongly expressed in the liver but it can be also found in lymphocytes. As such, lymphocyte may provide a non-invasive accessible pool for screening CYP2E1 expression in man. We have, therefore, analysed CYP2E1 expression and activity in lymphocyte microsomes from 12 healthy controls, 11 type 1 and 12 type 2 diabetic subjects by using Western blot and enzymatic activities. Immunoblotting did not show difference among CYP2E1 protein bands in controls, type 1 and type 2 diabetics. To assess CYP2E1 activity we used the 7-ethoxy-4-trifluoromethylcoumarin (7-EFC), as a fluorescent substrate. The rate of deethylation of 7-EFC from controls did not differ from type 1 and type 2 diabetic subjects. The lack of any difference in CYP2E1 activity also was confirmed by the NADPH-dependent microsomal lipid peroxidation CCL4-induced assay showing similar peroxidation rates among controls and diabetic subjects. The results show that CYP2E1 expression/activity in lymphocytes is not enhanced in diabetes.     

Involvement of the cannabimimetic compound, N-palmitoyl-ethanolamine, in inflammatory and neuropathic conditions: Review of the available pre-clinical data, and first human studies

The endogenous cannabimimetic compound, and anandamide analogue, N-palmitoyl-ethanolamine (PEA), was shown to exert potent anti-inflammatory and analgesic effects in experimental models of visceral, neuropathic and inflammatory pain by acting via several possible mechanisms. However, only scant data have been reported on the regulation of PEA levels during pathological conditions in animals or, particularly, humans. We review the current literature on PEA and report the results of three separate studies indicating that its concentrations are significantly increased during three different inflammatory and neuropathic conditions, two of which have been assessed in humans, and one in a mouse model. In patients affected with chronic low back pain, blood PEA levels were not significantly different from those of healthy volunteers, but were significantly and differentially increased (1.6-fold, P<0.01, N = 10 per group) 30 min following an osteopathic manipulative treatment. In the second study, the paw skin levels of PEA in mice with streptozotocin-induced diabetic neuropathic pain were found to be significantly higher (1.5-fold, P<0.005, N = 5) than those of control mice. In the third study, colonic PEA levels in biopsies from patients with ulcerative colitis were found to be 1.8-fold higher (P<0.05, N = 8–10) than those in healthy subjects. These heterogeneous data, together with previous findings reviewed here, substantiate the hypothesis that PEA is an endogenous mediator whose levels are increased following neuroinflammatory or neuropathic conditions in both animals and humans, possibly to exert a local anti-inflammatory and analgesic action.     

Effectiveness of Nutritional Supplementation on Muscle Mass in Treatment of Sarcopenia in Old Age: A Systematic Review

BackgroundMuch interest has been focused on nutritional treatment of sarcopenia, loss of muscle mass and performance associated to aging; however, its benefits are unclear.ObjectiveTo analyze the relevance of nutritional treatment of sarcopenia and assess the effects of supplementation on muscle mass and function within the aged population.MethodsWe searched Medline and the Cochrane Library for controlled trials published between 1991 and 2012. We have assessed the quality, type of intervention, the cohort used, the way muscle mass was measured, and the outcomes of the various studies.ResultsWe have included 17 studies, with a total of 1287 patients, aged between 65 and 85 on average. An improvement in muscle mass was proven, whether measured with bioelectrical impedance analysis or dual energy x-ray absorptiometry, and an improvement in strength was also proven.ConclusionNutritional supplementation is effective in the treatment of sarcopenia in old age, and its positive effects increase when associated with physical exercise. The main limitation of this treatment is lack of long-term adherence. A healthy diet associated with a physically active lifestyle and possibly with aerobic exercise are the basis of healthy aging, which is the aim of all doctors treating aged people must seek.     

Idiopathic Facial Aseptic Granuloma in a Child: A Possible Expression of Childhood Rosacea

Abstract: Idiopathic facial aseptic granuloma is a chronic, benign, and painless facial nodule occurring exclusively in childhood. Its pathogenesis is unclear, although some interesting hypotheses have been advanced. On the basis of the relationship existing between this disease and recurrent chalazions and conjunctivitis, we hypothesize that it could be considered to be a possible marker of childhood rosacea.     

Analysis and Comparison of Friction Stir Welding and Laser Assisted Friction Stir Welding of Aluminum Alloy

Friction Stir Welding (FSW) is a solid-state joining process; i.e., no melting occurs. The welding process is promoted by the rotation and translation of an axis-symmetric non-consumable tool along the weld centerline. Thus, the FSW process is performed at much lower temperatures than conventional fusion welding, nevertheless it has some disadvantages. Laser Assisted Friction Stir Welding (LAFSW) is a combination in which the FSW is the dominant welding process and the laser pre-heats the weld. In this work FSW and LAFSW tests were conducted on 6 mm thick 5754H111 aluminum alloy plates in butt joint configuration. LAFSW is studied firstly to demonstrate the weldability of aluminum alloy using that technique. Secondly, process parameters, such as laser power and temperature gradient are investigated in order to evaluate changes in microstructure, micro-hardness, residual stress, and tensile properties. Once the possibility to achieve sound weld using LAFSW is demonstrated, it will be possible to explore the benefits for tool wear, higher welding speeds, and lower clamping force.     

Preliminary Evaluation of the Safety and Efficacy of Standard Intravenous Immunoglobulins in Pregnant Women with Primary Cytomegalovirus Infection

Hyperimmune globulins were reported to prevent and treat fetal cytomegalovirus (CMV) infection during pregnancy. Here, we report that infusions of standard human intravenous immunoglobulin significantly increase CMV IgG titers and avidity indexes in pregnant women, paving the way to their use for passive transfer of maternal CMV humoral immunity to fetuses. Preliminary data on perinatal outcomes of the first 67 newborns are encouraging.     

Pseudomembranous collagenous colitis with superimposed drug damage

Pseudomembranous collagenous colitis is a rare pathological condition, not related to infectious agents, and characterized by thickening of the subepithelial collagen and formation of pseudomembranes. We report one such case, which responded to budesonide treatment after failures of previous approaches given, being unaware of the correct diagnosis.