Usefulness of frozen-section examination in resected mid-rectal cancer after preoperative radiation

The surgical treatment of rectal cancer of the middle third remains controversial. We treated 30 consecutive patients with preoperative radiotherapy (45 Gy) and low anterior resection. Anastomoses were performed with a stapler. Intraoperative frozen-section examination of the rectal margin established that it was free of tumor. Two patients died of surgery-related causes. Median follow-up of the remaining patients is now 52 months (range: 26 to 76 months). Eight patients had recurrences documented at surgical re-exploration: two local (pelvic) only, three local and distant, and two distant only. Local recurrences happened despite a frozen-section examination of the rectal margin negative for tumor. Six of the eight patients who experienced a recurrence have died of disease progression. Distant metastases were found in six other patients during follow-up; they subsequently died. Thus, our therapeutic approach was not associated with decreases in local or overall recurrences.     

Effects of general anaesthetic procedures on mitochondrial function of human skeletal muscle

Background: General anaesthetics inhibit mitochondrial function in animal models. However, very few studies have been performed in humans, and the results have not been conclusive. Methods: We prospectively studied the oxygen consumption and the individual enzyme activity of each complex of the mitochondrial respiratory chain of skeletal muscle mitochondria in 54 healthy individuals who underwent general anaesthesia for orthopaedic surgery. The control group (n = 54) was made up of individuals submitted to the same orthopaedic procedure under regional anaesthesia (n = 31), and patients who underwent muscle biopsies for diagnostic purposes by local anaesthesia (n = 23). Results: We found a significant decrease in the oxidation of glutamate (−36%), succinate (−25%) and ascorbate (−29%) in the general anaesthetic group compared with the controls (P < 0.001 for all substrates). The level of such inhibition was similar for volatile anaesthetics with strong (halothane) or weak (isoflurane) negative inotropic effect. By contrast, the enzymatic activity of all individual complexes and the coupling of oxidative phosphorylation did not differ between the two groups. Conclusion: We conclude that during general anaesthetic procedures there is an extensive inhibition of substrate oxidation in human muscle mitochondria, and that it is not caused by a direct effect on complexes of the mitochondrial respiratory chain or through uncoupling oxidative phosphorylation. Received: 27 July 1998 / Accepted in revised form: 27 October 1998     

Obstetric trauma. A current problem?

Advances in obstetric practice have decreased birth traumas in the last years, although they are still an important chapter in neonatal age. Between 1993-1998 a total of 21,375 stillborns were registered with a total of 309 birth injuries in 303 neonates (1.44%). The diagnoses were: 2 liver subcapsular hematomas, 105 cephalohematomas, 16 parietal fractures, 11 subdural hemorrhages, 107 clavicular fractures, 10 miscellaneous fractures, 8 soft tissue injuries, 25 facial nerve injuries and 25 braquial palsy. About relation between type of labor and birth trauma was found that clavicular fracture and cephalic vaginal delivery were associated in 50% of the cases, cephalohematoma and forceps in 51%, braquial palsy and vaginal delivery in 44% and forceps in 36%. High weight at birth was another risk factor for entities such as clavicular fracture and braquial palsy. We conclude that birth trauma is a pathology with a relevant incidence and their epidemiology factor had to be known.     

Absence of mitochondrial dysfunction in polymyalgia rheumatica. Evidence based on a simultaneous molecular and biochemical approach

OBJECTIVE: To investigate the molecular and biochemical profile of skeletal muscle mitochondria of patients with isolated polymyalgia rheumatica (PMR). PATIENTS AND METHODS: We included patients with a recent diagnosis of PMR and as control healthy individuals submitted to orthopedic surgery. Skeletal muscle was obtained from quadriceps, thus was mitochondria immediately isolated. Long polymerase chain reaction and Southern blot transference were performed to detect deleted mtDNA molecules. Mitochondrial oxidative activity using different substrates and individual enzyme activity of respiratory chain complexes were assessed to search for any biochemical dysfunction. RESULTS: Fifty-one individuals (PMR=25, controls=26) were included. Mean age was 72 (11) years; 45% were females. We found no significant increase of deleted mtDNA molecules in PMR patients compared to controls. Both groups differed neither on oxygen consumption (p=NS for all substrates) nor enzymatic activity (p=NS for all complexes). CONCLUSIONS: Skeletal muscle mitochondria are molecularly and biochemically unaffected in PMR.     

Inhibitor kinazy Brutona u chorych z nawrotowym lub opornym na leczenie chłoniakiem z komórek płaszcza – wyniki międzynarodowego,wieloośrodkowego,badania II fazy z ibrutynibem (PCI-32765) – EHA Encore

Bruton's tyrosine kinase (BTK) is a central mediator of B-cell receptor (BCR) signaling essential for normal B-cell development. Ibrutinib is an oral BTK inhibitor that induces apoptosis and inhibits migration and adhesion of malignant B-cells. Updated results of this international, multicenter, phase 2 study of single agent ibrutinib in relapsed or refractory MCL will be presented.Ibrutinib 560 mg PO QD was administered continuously until disease progression. Tumor response was assessed every 2 cycles (one cycle = 28 days). The study enrolled 115 patients (65 bortezomib-naïve, 50 bortezomib-exposed); 111 patients were treated; 110 were evaluable for response. Baseline characteristics included: median age 68 years, time since diagnosis 42 months, number of prior treatments 3; bulky disease (>10 cm) 13%, prior stem cell transplant 10%, high risk MIPI 49%.Median time on treatment was 9.2 months; 53% of patients remain on therapy. Median PFS was 13.9 months and DOR has not yet been reached. Responses increased with longer treatment: comparing to previous data described at ASH 2011, the CR rate increased from 16% to 39%, and the ORR increased from 69% to 75%.     

Expression of fibroblast growth factor-2 and brain-derived neurotrophic factor mRNA in the medial prefrontal cortex and hippocampus after uncontrollable or controllable stress

Neurotrophic factors, including basic fibroblast growth factor (FGF-2) and brain-derived neurotrophic factor (BDNF) are known to be affected by exposure to stressful experiences. Here, we examine the effects of behaviorally controllable (escapable tailshock, ES) or uncontrollable (inescapable tailshock, IS) stress on the expression of FGF-2 and BDNF mRNA in subregions of the medial prefrontal cortex (mPFC) and the hippocampal formation (HF) of male Sprague-Dawley rats. ES rats were placed in Plexiglas boxes equipped with a free spinning wheel and IS rats were placed in identical boxes with the wheels fixed. ES and IS rats were yoked such that they received the same tailshocks, but the ES rat could terminate each shock for both rats. No stress controls (NS) remained in their home cages. Rats were killed 0, 2, 24, or 72 h after termination of the stress session. In situ hybridization was performed to measure FGF-2 and BDNF mRNA in the mPFC and HF. In the mPFC, ES produced a significant increase in FGF-2 mRNA expression at 0 and 2 h post-stress. In the HF, ES produced a greater increase in FGF-2 mRNA expression than IS and NS only in CA2. ES also produced an increase in BDNF mRNA expression in the anterior cingulate at 0 h post-stress. No effects of stressor controllability on BDNF were observed in the HF, although both ES and IS decreased BDNF mRNA in the DG. FGF-2 in the mPFC may be involved in emotional regulation ("coping") during stressful experiences.