Inflammation in prostate cancer progression and therapeutic targeting

Chronic inflammation contributes to the onset and progression of human cancer, via modifications in the tumor microenvironment by remodeling the extracellular matrix (ECM) and initiating epithelial mesenchymal transition (EMT). At the biological level, chronically inflamed cells release cytokines that are functionally dictating a constitutively active stroma, promoting tumor growth and metastasis. In prostate cancer, inflammation correlates with increased development of “risk factor” lesions or proliferative inflammatory atrophy (PIA). Chronic inflammation in benign prostate biopsy specimens can be associated with high-grade prostate tumors in adjacent areas. In this article, we discuss the current understanding of the incidence of inflammation in prostate cancer progression and the significance of the process in therapeutic targeting of specific inflammatory signaling pathways and critical effectors during tumor progression. Further understanding of the process of chronic inflammation in prostate tumor progression to metastasis will enable development and optimization of novel therapeutic modalities for the treatment of high-risk patients with advanced disease.     

Ten years of mechanical complications of central venous catheterization in trauma patients

The study purpose was to determine the incidence of mechanical complications (MC) associated with central venous catheterization (CVC) and to evaluate their impact on outcomes. This was a retrospective review of trauma morbidity and mortality records at a Level I trauma center (1999 to 2009). Demographics and outcomes were extracted for all trauma patients with CVC. Patients developing MC were compared with those who did not. Four thousand eight hundred eighteen lines were placed in 2935 patients. Of these, 1.5 per cent (n = 73) had MC. A total of 64.4 per cent (n = 47) were pneumothoraces followed by arterial cannulation at 8.2 per cent (n = 6) and thrombosis at 6.8 per cent (n = 5). The rate of MC by access site was: subclavian 1.8 per cent (n = 52), internal jugular 1.2 per cent (n = 10), and femoral 0.3 per cent (n = 3) (P value for trend = 0.001). Change in management was required in 31.5 per cent (n = 23). Number of lines (P < 0.001), Injury Severity Score (P < 0.001), body mass index less than 20 kg/m(2) (P = 0.036), and chest Abbreviated Injury Score greater than 3 (P = 0.034) were significant predictors of MC. Patients with MC had a longer intensive care unit length of stay (18.8 ± 25.7 vs 11.4 ± 13.3; adjusted odds ratio, 5.75; 95% confidence interval, 2.24-9.25; P = 0.001). Incidence of MC was 1.5 per cent. Complications were clinically significant in 31.5 per cent and resulted in longer intensive care unit stays.     

Endovascular treatment of cranial arteriovenous malformations and dural arteriovenous fistulas

Pial arteriovenous malformations (AVMs) and dural arteriovenous fistulas (DAVFs) are high-flow vascular lesions with abnormal communications between the arterial and venous system. AVMs are congenital lesions, whereas DAVFs are considered acquired lesions. Both can cause significant morbidity and mortality if they rupture and result in intracranial hemorrhage. The primary goal of treatment is to eliminate the risk of bleeding or at least decrease it. Because the epidemiology, clinical presentation, and classification of AVMs and DAVFs have been covered in previous articles in this issue, the authors only briefly touch on these subjects as they relate to endovascular treatment.     

Protoporphyrin accumulation by mitogen stimulated lymphocytes and protoporphyrinogen oxidase activity in patients with porphyria variegata and erythropoietic protoporphyria: evidence for deficiency of protoporphyrinogen oxidase and ferrochelatase in both diseases

In erythropoietic protoporphyria (EPP) and porphyria variegata (PV) excess protoporphyrin is excreted in the stool, suggesting one or more enzyme defects in the terminal steps of the haem biosynthetic pathway. We measured protoporphyrinogen oxidase (PPO), which catalyses the oxidation of protoporphyrinogen to protoporphyrin, in both EPP and PV patients and in the offspring of PV patients. In the same subjects we measured protoporphyrin formation by mitogen stimulated lymphocytes, with delta aminolaevulinic acid (ALA) as substrate and with the addition of chelators or iron, an indirect measure of ferrochelatase activity. PPO activity was reduced by 41% (P less than 0.001) in PV patients and in 50% of their offspring, and by 36% (P less than 0.001) in EPP patients. Protoporphyrin accumulation in stimulated lymphocytes was increased by 1.3-fold (P less than 0.001) in EPP and 1.5-fold (P less than 0.001) in PV patients compared to normal subjects. There was a significant difference in protoporphyrin accumulation between iron deficient and iron replete cells from PV patients as compared to normals but not as marked as for EPP cells treated similarly. Stimulated lymphocytes from prepubertal PV offspring with reduced PPO activity accumulated normal amounts of protoporphyrin. We have interpreted our findings as follows: PPO is significantly reduced in both diseases. Ferrochelatase becomes defective in PV patients after puberty. This could explain why PV is clinically and biochemically manifest only after puberty. As it has been repeatedly shown that ferrochelatase is markedly reduced in EPP, it would appear that both enzymes are deficient in these two porphyrias.     

Clinical effect of abdominal aortic aneurysm endografting: 7-year concurrent comparison with open repair

OBJECTIVE: We compared the effectiveness and clinical outcome of open repair versus endovascular aortic aneurysm repair (EVAR) in achieving prevention of abdominal aortic aneurysm (AAA)-related death and graft-related complications. METHODS: Over 7 years from 1997 to 2003, 1119 consecutive patients underwent elective treatment of infrarenal AAAs, 585 with open repair and 534 with EVAR. Patients were regularly followed up at 1, 6, 12 months, and every 6 months thereafter, in EVAR group, and at 3 and 12 months, and yearly thereafter after open repair. Preoperative, intraoperative, and follow-up data were stored in a prospective database. RESULTS: Median follow-up was similar in the 2 groups: 33 months (interquartile range [IQR], 13-50 months) in the EVAR group vs 35 months (IQR, 15-54 months) in the open repair group. EVAR group patients were older than patients in the open repair group: 73 years vs 72 years (P = .04). There were statistical significant differences between the EVAR group and the open repair group with respect to AAA median diameter (52 mm vs 56 mm), coronary disease rate (46% vs 37%; P = .001), pulmonary disease rate (56% vs 38%; P < .0001), and American Society of Anesthesiologists IV score rate (16% vs 6%; P < .0001). Thirty-day mortality in the EVAR group was 0.9% (5 of 534 patients), compared with 4.1% (24 of 585 patients; P = .001) in the open repair group, and major morbidity was 9.1% (49 of 534 patients) vs 18.6% (109 of 585 patients; P < .0001), respectively. The incidence of secondary procedures in the EVAR group was 15.7%, compared with 3% in the open repair group (P < .0001). There were no deaths related to secondary procedures in either group. Six AAAs (1.1%) ruptured after EVAR, 3 of which were fatal; in the open repair group 1 patient (0.2%) underwent successful repeat operatation to treat iliac pseudoaneurysm rupture 5 years after the original procedure. Kaplan-Meier estimates for freedom from aneurysm-related death at 84 months were 97.5% in the EVAR group and 95.9% in the open repair group (log rank test, P = .008). Kaplan-Meier survival estimates at 84 months were 67.1% in the open repair group and 66.9% in the EVAR group (P = NS). At the same interval the risk for secondary procedures was 49.4% for the EVAR group and 7.1% for the open repair group. Of the 11 variables analyzed with logistic analysis, open surgery (hazard ratio [HR], 11; 95% confidence interval [CI], 2.5-54.2; P = .002), American Society of Anesthesiologists IV score (HR, 7.1; 95% CI, 2.7-18.8; P = .0001), and age (HR, 1.06; 95% CI, 1.04-1.13; P = .04) were positive independent predictors of perioperative mortality. CONCLUSION: Our data suggest that at a maximum follow-up of 7 years, patients who undergo EVAR show lower perioperative and late aneurysm-related mortality compared with a younger and substantially healthier group of patients with aneurysms treated with open repair. The higher need for secondary procedures in the endovascular group did not affect superiority of the overall performance of EVAR in the early and late intervals.     

Risk of Glove Perforation in Minor and Major Plastic Surgery Procedures

Background Incidental needlestick injury with exposure of blood pathogens has a high incidence among health care workers. Because plastic surgeons make up an important risk group for this type of accident, this study sought to evaluate the incidence of glove perforation during minor and major plastic surgery procedures.Methods Evidence of glove perforation was evaluated for 390 gloves after 100 consecutive minor surgical procedures and for 710 gloves after 100 consecutive major surgeries using Maffulis test. An index based on the number of first assistants glove perforation and the surgical time was created to compare these accidents associated with both types of procedures.Results Glove perforations were found in four gloves (1.02%) after minor surgery and 76 gloves (21.40%) after major surgery. During minor surgeries, the assistant was more likely to have exposure than the surgeon. During major surgery, the surgeon experienced more glove perforations (59.21%) than the assistant (40.79%). The most common location of perforations was the palmar face of the left hand in both groups. The surgeons did not notice these perforations at any time. The duration of the minor procedures varied from 10 to 30 min (average, 17.55 min), whereas the time of major procedures ranged from 1 to 6 h (average, 186 min). There was no statistical significant difference in the perforations index between minor and major procedures.Conclusions The risk of perforation to the surgeons glove during minor surgery is minimal. The frequency of perforation to the first assistants glove is similar between minor and major plastic surgery procedures.     

Applied anatomy of the fasciocutaneous branch of the third perforator artery of the deep femoral artery

A study of the anatomy of the fasciocutaneous branch of the third perforator artery of the deep femoral artery was performed to help the elaboration of a fasciocutaneous flap for the reconstruction of skin and subcutaneous and deep fascia of the knee and popliteal region.Forty thighs in 27 fresh cadavers were dissected. In all of the thighs, the third perforator artery was found to arise from the deep femoral artery and reach the posterior aspect of the thigh after perforating the adductor magnus muscle. At that point it was also found that the third perforator artery gives off a branch that emerges through the intermuscular septum between the vast lateral muscle and the long head of the biceps femoral muscle, then crosses the posterior cutaneous nerve and moves directly on to perforate the deep fascia and then to bifurcate into two other branches: one ascending and one descending.The cutaneous area of the flap of the thigh’s posterior region, nourished by the fasciocutaneous branch, was evaluated through the injection of dye. Dying of the upper medial, middle medial, lower medial and lower lateral areas of the flap was not successful in all of the dissected thighs. Nevertheless, the upper lateral and the middle lateral areas were dyed successfully in all 40 dissected thighs of the 27 cadavers.     

A GABRB3 promoter haplotype associated with childhood absence epilepsy impairs transcriptional activity

Human     

Effect of nicotine treatment and withdrawal on random-pattern skin flaps in rats

BACKGROUND: Tobacco use is associated with a high incidence of skin necrosis after surgery. The ideal timing for the cessation of tobacco use before plastic surgery has not, however, been precisely determined. The aim of this work was to define the ideal duration of nicotine withdrawal prior to random-pattern skin flap surgery in rats. METHODS: Groups of 11 animals were subcutaneously injected with saline or nicotine (2mg/kg) twice a day and subjected to random-pattern skin flap surgery according to the following protocol: Group I: continuously injected with saline 4 weeks before and 1 week after the surgery; Group II: injected with nicotine for 4 weeks until the day of the surgery; Group III: injected with nicotine for 4 weeks until one day before the surgery; Group IV: injected with nicotine for 4 weeks until 5 days before the surgery; Group V: injected with nicotine for 4 weeks until 10 days before the surgery; Group VI: continuously injected with nicotine for 4 weeks before and 1 week after the surgery. McFARLANE skin flaps were performed on the dorsal skin, and the rats were sacrificed 1 week after the surgery. RESULTS: The necrotic area was smaller in group I (8.85cm(2)) than in group II (12.15cm(2)), III (12.88cm(2)) and VI (14.84cm(2)) (ANOVA p<0.0001). There was no difference between groups I, IV (10.13cm(2)) and V (9.27cm(2)). CONCLUSIONS: In conclusion, 5 days before surgery was considered the ideal time for nicotine withdrawal in this experimental model.