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Extracranial carotid artery aneurysm is a rare condition with relatively significant morbidity and mortality. When surgery is not indicated, endovascular techniques are emerging as the preferred treatment. However, even this approach may be contraindicated due to anatomic factors. We present a case of a high-lying extracranial carotid artery aneurysm with challenging anatomy unsuitable for conventional or endovascular repair. After resecting the aneurysm, the carotid artery was revascularized using the new Gore Hybrid Vascular Graft (W. L. Gore & Associates, Flagstaff, Ariz). This straightforward procedure turned out to be safe and further reduced the cerebral ischemic time., (Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

The role of protein kinase C epsilon (PKC epsilon) in polymorphonuclear leukocyte (PMN)-induced myocardial ischemia/reperfusion (MI/R) injury and novel-related mechanisms, such as regulation of vascular endothelium nitric oxide (NO) and hydrogen peroxide (H2O2) release from blood vessels, have not been previously evaluated. A cell-permeable PKC epsilon peptide activator (1-10 microM) significantly increased endothelial NO release from non-ischemic rat aortic segments (p < 0.01). By contrast, PKC epsilon peptide inhibitor (1-10 microM) dose-dependently decreased NO release (p < 0.01). Then, these corresponding doses of PKC epsilon activator or inhibitor were examined in MI/R. The PKC epsilon inhibitor (5 microM given during reperfusion, n=6) significantly attenuated PMN-induced postreperfused cardiac contractile dysfunction and PMN adherence/infiltration (both p < 0.01), and expression of intracellular adhesion molecule-1 (ICAM-1; p < 0.05). By contrast, only PKC epsilon activator pretreated hearts (5 muM PKC epsilon activator given before ischemia (PT), n = 6), not PKC epsilon activator given during reperfusion (5 microM, n=6) exerted significant cardioprotection (p < 0.01). Moreover, the NO synthase inhibitor, N(G)-nitro-L: -arginine methyl ester, did not block the cardioprotection of PKC epsilon inhibitor, whereas it completely abolished the cardioprotective effects of PKC epsilon activator PT. In addition, PKC epsilon inhibitor (0.4 mg/kg) significantly decreased H(2)O(2) release during reperfusion in a femoral I/R model (p < 0.01). Therefore, the cardioprotection of PKC epsilon inhibitor maybe related to attenuating ICAM-1 expression and H2O2 release during reperfusion. By contrast, the cardioprotective effects of PKC epsilon activator PT may be mediated by enhancing vascular endothelial NO release before ischemia.

The proven antiangiogenic activity of zoledronic acid, a third-generation bisphosphonate widely used in bone metastatic cancer patients, led us to investigate if the vascular endothelial growth factor (VEGF)-related zoledronic acid modifications are correlated with survival advantages in advanced breast cancer patients. Forty-two consecutive breast cancer patients with scintigraphic and radiographic evidence of bone metastases were treated with a single infusion of 4 mg zoledronic acid before anticancer chemotherapy. The patients were prospectively evaluated for circulating levels of VEGF and interferon-gamma (IFN-gamma) just before and at 1, 2, 7, and 21 days after zoledronic acid infusion. Afterward, clinical outcome was prospectively monitored. The basal serum VEGF median levels were significantly decreased at each time point, but the major reduction was recorded 21 days after the infusion. In particular, 25 patients of 42 (59.5%) experienced a reduction of at least 25% in the VEGF circulating levels. In contrast, no statistically significant modifications of the IFN-gamma serum levels were recorded. We stratified patients on the basis of this VEGF reduction 21 days after the infusion. No differences in patient features were recorded between those with or without the VEGF reduction. The analysis of survival showed that patients with a reduction in the VEGF circulating levels had a longer time to first skeletal-related event (p = 0.0002), time to bone progression disease (p = 0.0024), and time to performance status worsening (p = 0.0352) than those without the VEGF reduction. No statistically significant differences were recorded in terms of overall survival and time to visceral progression. This study confirms that zoledronic acid could have an in vivo antiangiogenic property and that the VEGF modifications may represent a surrogate marker able to predict time to first skeletal-related event, time to bone progression disease, and time to worsening of performance status.

Colorectal cancer represents a major health problem in the western world. A lot of drugs have been employed in treatment of this disease, but only few data are available about predictive factors for response to anticancer treatments in colorectal cancer. Aim of this paper is to review the main data about this investigation field. Using a Medline database search (1966-2003) we reviewed all the relevant papers that investigate clinical and molecular predictors for response to the main drugs used in the treatment of colorectal cancer patients, both in adjuvant and in advanced setting. Moreover we comprehensively reviewed all the data published in abstract form during the most significant international meetings. Our review put in evidence the most important predictive factors for response in colorectal cancer patients treated with anticancer chemotherapy both in adjuvant and in advanced setting. The predictive factors are clustered on the basis of the different anticancer drugs. The results of this review provide the rationale basis for personalizing anticancer treatment in colorectal cancer patients by molecular and clinical features, aiming to improve response rate and reduce toxicities.

Objectives: We retrospectively evaluated the relevance of thymidylate synthase (TS) expression in normal colonic mucosa as a predictive factor of toxicity in colorectal cancer patients receiving adjuvant fluorouracil (5-FU)-based chemotherapy., Methods: TS expression was immunohistochemically assessed on normal colonic mucosa from 50 patients with colorectal cancer Dukes' stages B (15 patients) and C (35 patients) treated with 5-FU-based adjuvant chemotherapy., Results: The incidence of grade 2-3 diarrhea and stomatitis (according to WHO) was demonstrated to be significantly higher in patients with low nuclear TS expression in normal mucosa than in those with high TS expression (p < 0.0001). Moreover, patients with low TS expression in normal colonic mucosa developed weight loss and worsening of the performance status (according to ECOG score) more commonly than patients with high TS expression (p = 0.005 and p = 0.02, respectively). Furthermore, low TS expression in normal colonic mucosa significantly correlated with a higher rate of a delay of chemotherapy courses, dose reduction and treatment discontinuation., Conclusions: Immunohistochemical TS expression in normal colonic mucosa may represent an important predictive parameter for identifying a subset of patients with a high risk of developing severe 5-FU-related toxicities., (2004 S. Karger AG, Basel.)

Evaluation of arm work capacity after radical neck surgery. The aim of this paper is to describe an approach for the assessment of work capacity in patients who underwent radical neck surgery, including those treated with radiation therapy. Nine male patients, who underwent radical neck surgery 2 months before being referred to our Unit, participated in the study. In addition to manual muscle strength test, we performed the following functional evaluations: 0-100 Constant scale for shoulder function; maximal shoulder strength in adduction/abduction and intrarotation/extrarotation; instrumental. We measured maximal isokinetic strength (10 repetitions) with a computerized dynamometer (Lido WorkSET) set at 100 degrees/sec. During the rehabilitation phase, the patients' mechanical parameters, the perception of effort, pain or discomfort, and the range of movement were monitored while performing daily/occupational task individually chosen on the simulator (Lido WorkSET) under isotonic conditions. On this basis, patients were encouraged to return to levels of daily physical activities compatible with the individual tolerable work load. The second evaluation at 2 month confirmed that the integrated rehabilitation protocol successfully increased patients' capacities and "trust" in their physical capacity. According to the literature, the use of isokinetic and isotonic exercise programs appears to decrease shoulder rehabilitation time. In our experience an excellent compliance has been noted. One of the advantages of the method proposed is to provide quantitative reports of the functional capacity and therefore to facilitate return-to-work of patients who underwent radical neck surgery.

Cancer patients are now more often long-term survivors and their needs for returning to social and productive activities have become a primary focus of intervention. The purpose of the present study was to propose an objective evaluation test for predicting endurance capacity in breast cancer patients after surgery, in order to optimize return to work or previous daily activities, and for monitoring changes during rehabilitation. Twenty female patients (mean age: 44 +/- 5), who underwent radical breast surgery 2 months before being referred to our Unit, participated in the study. In addition to the measures of the circumferences in the arm-forearm and manual muscle strength test, we performed the following functional evaluations: 0-100 Constant scale for shoulder function; instrumental evaluation of daily/occupational upper limb activities (Lido WorkSET). We monitored the mechanical parameters, the perception of effort, pain or discomfort, and the range of movement while performing a 3-minute steady daily/occupational task chosen by the subject. Patients were asked to perform the 3-minute test at three different intensities ("moderate", "somewhat hard", "hard") until the perception of fatigue, pain or discomfort was rated > 3 on the 10 point Borg's scale. The 'power-duration' product (Watt x min) defined by the three tests (see Fig. 1) represented the individual tolerable work load, since subjective indicators of pain/discomfort remained within tolerable limits during the exertion. On this basis, patients were encouraged to return to levels of daily physical activities compatible with the individual tolerable work load. The second evaluation, although no statistical analysis was performed, confirmed that the "guided" daily activity in a 2-month period increased patients' capacities and "trust" in their physical capacity.

Occupational specialists are well aware of the lack of objective measurements for the diagnosis and the functional evaluation of workers affected by thoracic outlet syndrome (TOS). Subjects affected by TOS refer pain, sensation of fatigue in the arm frequently aggravated by overhead work. A "stick-up" position tends to close the costoclavicular space and tense the neck and shoulder muscles to bring into play the abnormal compression mechanism that may affect the brachial plexus nerves and the subclavian vessels. In a previous study, we demonstrated the reliability of an isokinetic hand grip endurance test. In this pilot study we asked 7 industrial workers affected by TOS to perform a 30-second isokinetic endurance test for hand gripping with a Lido WorkSET dynamometer. Tests were performed in two positions (resting and "stick-up" position) before and after a 3-week intensive rehabilitation program. In addition, the subjects performed daily aerobic exercise with an arm crank ergometer. Objective indexes of posttreatment improvement were found. Subjects were able to generate higher grip forces during the isokinetic hand grip endurance test and to sustain higher mechanical workload with the arm ergometer at the same intensity level for longer duration after completion of the rehabilitation program.

Accessible indicators for setting exertion levels in newly injured paraplegias could be useful to improve their daily and occupational performances in less time than is presently required. Eight male newly injured paraplegic subjects performed progressive resisted and endurance exercise tests on an arm cranking ergometer. Cardiorespiratory parameters during exercise were monitored with an oxygen uptake analyzer and perceived exertion was rated on Borg's 10-point scale. Four subjects (Group A) underwent an 'enhanced' rehabilitation protocol which included aerobic arm training sessions. The prescription of exercise intensity was tailored to each subject's tolerable power output for prolonged exertion. The remaining four (Group B) followed a 'conventional' rehabilitation program. Tests were repeated in both groups after 6 weeks. We observed a greater improvement in endurance capacity in Group A than in Group B after completion of the rehabilitation program. A 6-week 'enhanced' rehabilitation program based on a 'moderate' intensity of exercise was well tolerated and effective in improving the fitness levels of newly injured paraplegic subjects. Subjective perception has been shown to be a simple and accessible indicator for setting exertion levels.

Idiopathic pulmonary hemosiderosis (IPM) is a rare disease of unknown etiology, whose diagnostic, prognostic and therapeutic approach is still open to discussion. In this paper the authors report a study regarding three cases of IPH initially detected in 13, 11 and 7 year-old children. The patients were treated with cyclophosphamide and prednisone according to different cycles depending on the clinical stage in the disease. All three patients are still alive after 10, 6 and 5 years since initial diagnosis. This therapeutic protocol therefore seems to be effective in preventing the progression of IPH and in maintaining the patients in an asymptomatic condition.