Colorectal resection,both open and laparoscopic-assisted,in patients with benign indications is associated with proangiogenic changes in plasma angiopoietin 1 and 2 levels

Introduction  Plasma vascular endothelial growth factor (VEGF) levels are increased after surgery and may stimulate tumor growth after cancer resection. Angiopoietin 1 (Ang 1) and Ang 2 are proteins that impact VEGF-related angiogenesis (VRA). Ang 1 stabilizes mature vessels and inhibits VRA, whereas Ang 2 destabilizes vessels and promotes VRA. The ratio of Ang 1 to Ang 2 reflects the net effect; a low ratio promotes VRA. This study’s purpose was to determine the impact of open and minimally invasive (MIS) colorectal resection (CR) for benign indications on plasma Ang 1 and 2 levels. Methods  A total of 30 patients operated by MIS and 26 operated by open procedure were studied. Plasma was obtained preoperatively (PO) and on postoperative days (POD) 1 and 3. Plasma Ang 1 and Ang 2 levels were assessed via enzyme-linked immunosorbent assay (ELISA) in duplicate. Data were compared using Wilcoxon’s matched-pair test and the Mann–Whitney U-test (significance p < 0.05). Results  Indications, types of resection, and morbidity for the groups were similar. The mean MIS incision length was 4.7 ± 1.6 cm while it was 16.8 ± 7.1 cm for the open group (p = 0.0001). For both groups Ang 2 levels were significantly higher and the Ang 1 to Ang 2 ratio was significantly lower on POD 1 and 3 compared with preoperative results. Ang 1 levels were significantly decreased on POD 1 and 3 in the MIS group but only on POD 1 in the open group. For unclear reasons, preoperative Ang 1 levels and Ang 1 to Ang 2 ratios were significantly different between the groups, which precludes comparison of the postoperative results between groups. Conclusion  CR for benign pathology results in higher Ang 2 levels, lower Ang 1 levels, and lower Ang 1 to Ang 2 ratios early after surgery. These alterations are proangiogenic. These results, plus the already noted VEGF increases, suggest that surgery results in proangiogenic plasma protein changes that may stimulate tumor growth early after surgery. The duration of the Ang 1 and 2 changes needs to be determined. An erratum to this article can be found at     

Is Minimal Access Surgery for Cancer Associated with Immunologic Benefits?

Minimal-access surgical techniques have been shown to be beneficial to patients in terms of shorter convalescence, reduced pain, and improved cosmesis. Although systemic immune function is better preserved following laparoscopic procedures when compared with their respective open approaches, CO₂ pneumoperitoneum may significantly affect local (i.e., infra-abdominal) cellular immunity by reducing regional macrophage function. Results to date are conflicting with regard to the impact of closed and open methods on intraabdominal immunity. Impaired cellular immunity after CO₂ pneumoperitoneum may have significant undesirable intra-abdominal effects on tumor surveillance after oncological surgery; however, at present, there is no clinical evidence to support this position. The VATS techniques avoid the use of CO₂ insufflation, which may offer some advantages from the immune function perspective over laparoscopic procedures accomplished with CO₂ pneumoperitoneum. Better preservation of early postoperative cellular immune function and attenuated disturbance in the inflammatory mediators are likely contributing factors to the clinical benefits that follow laparoscopic surgery and VATS. Larger multi-center randomized trials are needed to confirm the potential benefits of minimal-access surgery on patient survival after cancer surgery. Future research should focus on the effects of minimal-access surgery on other mediators (such as MMP-9, IGFBP-3, IL-12, IL-17, and IL-23) that may be important in tumor cell dissemination, deposition, and propagation in the early postoperative period. Furthermore, additional searches for other factors or mediators, heretofore unrecognized, should be carried out. Such studies will, we hope, increase our knowledge and understanding of the impact of surgery on immune and other physiologic functions.     

Minimally invasive colon resection is associated with a transient increase in plasma sVEGFR1 levels and a decrease in sVEGFR2 levels during the early postoperative period

Introduction  Plasma vascular endothelial growth factor (VEGF) levels are elevated for 2–4 weeks after minimally invasive colorectal resection (MICR). VEGF induces wound and tumor angiogenesis by binding to endothelial cell (EC)-bound VEGF-receptor 1 (VEGFR1) and VEGFR2. Soluble receptors (sVEGFR1, sVEGFR2) sequester VEGF in the blood and decrease VEGF’s proangiogenic effect. The importance of the MICR-related VEGF changes depends on the effect of surgical procedures on sVEGFR1 and sVEGFR2; this study assessed levels of these proteins after MICR for benign indications. Methods  Blood samples were taken (n = 39) preoperatively (preop) and on postoperative days (POD) 1 and 3; in most cases a fourth sample was drawn between POD 7 and 30. sVEGFR1 and sVEGFR2 levels were measured via enzyme-linked immunosorbent assay (ELISA), which detects free and VEGF bound soluble receptor. Late samples were bundled into POD 7–13 and POD 14–30 time points. Results are reported as mean and standard deviation. The data was assessed with paired-samples t-test. Results  Preop, mean plasma sVEGFR2 level (9,203.7 ± 1,934.3 pg/ml) was significantly higher than the sVEGFR1 value (132.5 ± 126.2 pg/ml). sVEGFR2 levels were significantly lower on POD 1 (6,957.8 ± 1,947.7 pg/ml,) and POD 3 (7,085.6 ± 2,000.2 pg/ml), whereas sVEGFR1 levels were significantly higher on POD 1 (220.0 ± 132.8 pg/ml) and POD 3 (182.7 ± 102.1 pg/ml) versus preop results. No differences were found on POD 7–13 or 14–30. Conclusions  sVEGFR2 values decreased and sVEGFR1 levels increased early after MICR; due to its much higher baseline, the sVEGFR2 changes dominate. The net result is less VEGF bound to soluble receptor and more free plasma VEGF.     

Mechanics of wound healing and importance of Vacuum Assisted Closure in urology

PURPOSE: We discuss the mechanisms of wound healing and our experience with the Vacuum Assisted Closure device (Kinetic Concepts, Inc., San Antonio, Texas) for complex urogenital wounds. MATERIALS AND METHODS: The literature obtained from a Medline search on wound healing, wound failure and vacuum assisted closure was reviewed. In addition, we reviewed our experience with negative pressure wound therapy. RESULTS: Wound healing is a complex interaction between the reticuloendothelial and immune systems, in addition to correctable internal and external factors. Understanding the healing process improves outcomes and decreases patient morbidity. Negative pressure wound therapy has hastened wound healing and it adds significant improvement in the arsenal of choices available. CONCLUSIONS: Vacuum Assisted Closure is a therapeutic alternative that complements surgical and medical intervention in patients with complex wounds.     

Effect of particle size on hydroxyapatite crystal-induced tumor necrosis factor alpha secretion by macrophages

Macrophages may promote a vicious cycle of inflammation and calcification in the vessel wall by ingesting neointimal calcific deposits (predominantly hydroxyapatite) and secreting tumor necrosis factor (TNF)alpha, itself a vascular calcifying agent. Here we have investigated whether particle size affects the proinflammatory potential of hydroxyapatite crystals in vitro and whether the nuclear factor (NF)-kappaB pathway plays a role in the macrophage TNFalpha response. The particle size and nano-topography of nine different crystal preparations was analyzed by X-ray diffraction, Raman spectroscopy, scanning electron microscopy and gas sorbtion analysis. Macrophage TNFalpha secretion was inversely related to hydroxyapatite particle size (P=0.011, Spearman rank correlation test) and surface pore size (P=0.014). A necessary role for the NF-kappaB pathway was demonstrated by time-dependent I kappaB alpha degradation and sensitivity to inhibitors of I kappaB alpha degradation. To test whether smaller particles were intrinsically more bioactive, their mitogenic activity on fibroblast proliferation was examined. This showed close correlation between TNFalpha secretion and crystal-induced fibroblast proliferation (P=0.007). In conclusion, the ability of hydroxyapatite crystals to stimulate macrophage TNFalpha secretion depends on NF-kappaB activation and is inversely related to particle and pore size, with crystals of 1-2 microm diameter and pore size of 10-50 A the most bioactive. Microscopic calcific deposits in early stages of atherosclerosis may therefore pose a greater inflammatory risk to the plaque than macroscopically or radiologically visible deposits in more advanced lesions.     

Ross River virus and Barmah Forest virus infections: a review of history, ecology, and predictive models, with implications for tropical northern Australia

The purpose of the present article is to present a review of the Ross River virus (RRV) and Barmah Forest virus (BFV) literature in relation to potential implications for future disease in tropical northern Australia. Ross River virus infection is the most common and most widespread arboviral disease in Australia, with an average of 4,800 national notifications annually. Of recent concern is the sudden rise in BFV infections; the 2005-2006 summer marked the largest BFV epidemic on record in Australia, with 1,895 notifications. Although not life-threatening, infection with either virus can cause arthritis, myalgia, and fatigue for 6 months or longer, resulting in substantial morbidity and economic impact. The geographic distribution of mosquito species and their seasonal activity is determined in large part by temperature and rainfall. Predictive models can be useful tools in providing early warning systems for epidemics of RRV and BFV infection. Various models have been developed to predict RRV outbreaks, but these appear to be mostly only regionally valid, being dependent on local ecological factors. Difficulties have arisen in developing useful models for the tropical northern parts of Australia, and to date no models have been developed for the Northern Territory. Only one model has been developed for predicting BFV infections using climate and tide variables. It is predicted that the exacerbation of current greenhouse conditions will result in longer periods of high mosquito activity in the tropical regions where RRV and BFV are already common. In addition, the endemic locations may expand further within temperate regions, and epidemics may become more frequent in those areas. Further development of predictive models should benefit public health planning by providing early warning systems of RRV and BFV infection outbreaks in different geographical locations.     

The Medical Treatment of Metastatic Renal Cell Cancer

Patients who present with or subsequently develop metastases from renal cell carcinoma still have a poor prognosis. However, in recent years the use of immunotherapy as either a single agent or in double or triple combinations has shown some welcome reproducible responses in this disease. Too much reliance, however, on phase II studies has tended to obscure the critical role of prognostic factors in the survival of patients with metastatic renal cell cancer. A critical analysis is offered with the current state of therapy and the exciting new fields of therapeutic research are discussed.