Prophylactic closed-incision negative-pressure wound therapy is associated with decreased surgical site infection in high-risk colorectal surgery laparotomy wounds.

AIM: Surgical site infection in colorectal surgery is associated with significant healthcare costs, which may be reduced by using a closed-incision negative-pressure therapy device. The aim of this study was to assess the impact of closed-incision negative-pressure therapy on the incidence of surgical site infection. METHOD: In this retrospective cohort study we evaluated all patients who had undergone high-risk open colorectal surgery at a single tertiary care centre from 2012 to 2016. We compared the incidence of surgical site infection between those receiving standard postoperative wound care between 2012 and 2014 and those receiving closed-incision negative-pressure therapy via a customizable device (Prevena Incision Management System, KCI, an Acelity company, San Antonio, Texas, USA) between 2014 and 2016. A validated surgical site infection risk score was used to create a 1:1 matched cohort subset. RESULTS: Negative pressure therapy was used in 77 patients and compared with 238 controls. Negative pressure patients were more likely to have a stoma (92% vs 48%, P < 0.01) and to be smokers (33% vs 15%, P < 0.01). Surgical site infection was higher in control patients (15%, n = 35/238) compared with negative pressure patients (7%, n = 5/77) (P = 0.05). On regression analysis, negative pressure therapy was associated with decreased surgical site infection (OR 0.27; 95% CI 0.09-0.78). These differences persisted in the matched analysis. CONCLUSION: Negative pressure therapy was associated with decreased surgical site infection. Negative pressure therapy offers significant potential for quality improvement.

Heterogeneity of colorectal cancer (CRC) in reference to KRAS proto-oncogene utilizing WAVE technology.

BACKGROUND: New drugs targeting specific genes required for unregulated growth and metastases have improved survival rates for patients with metastatic colorectal cancer. Resistance to monoclonal antibodies specific for the epidermal growth factor receptor (EGFR) has been attributed to the presence of activating point mutations in the proto-oncogene KRAS. The use of EGFR inhibitor monotherapy in patients that have KRAS wild type has produced response rates of only 10-20%. The molecular basis for clinical resistance remains poorly understood. We propose two possible explanations to explain these low response rates; 1) levels of resistant CRC cells carrying mutated KRAS are below the sensitivity of standard direct sequencing modalities (<5%) or 2) the standard practice of analyzing a single area within a heterogeneous tumor is a practice that can overlook areas with mutated KRAS. METHODS: In a collaborative effort with the surgical and molecular pathology departments, 3 formalin fixed paraffin embedded tissue blocks of human CRC were obtained from the human tissue bank maintained by the Lifespan Pathology Department and/or the human tissue bank maintained by the Molecular Pathology Core of the COBRE for Cancer Research Development. The three specimens previously demonstrated KRAS mutations detected by the Applied Biosystems Kit. The Wave system 4500 (high performance ion-pairing liquid chromatography (IP-HPLC)) was utilized to evaluate tissue for the presence of KRAS proto-oncogene mutations at codons 12 and 13. RESULTS: Initially, the sensitivity of WAVE technology was compared with direct sequencing by evaluating a dilutional series. WAVE detected mutant alleles at levels of 2.5% compared to 20% performed with standard direct sequencing. Samples from three patients were evaluated by WAVE technology. Eight samples from patient 1 were analyzed. In two of eight samples, no mutations were detected at concentrations as low as 5%. In one sample a mutation was noted by WAVE and not by direct sequencing. All four samples from patient 2 tested positive for Exon 12/13 mutations. Of the seven samples from patient 3, five were positive for Exon 12/13 mutations and two were negative for Exon 12/13 mutations. CONCLUSION: In these studies the analysis of three patients' colorectal cancer tissues were analyzed utilizing the WAVE technology. Results demonstrated a greater degree of sensitivity in mutation detection when compared to standard sequencing. These studies also demonstrated heterogeneity of expression of KRAS mutations between areas of the tissue samples at a genomic level. The low clinical response rates to EGFR inhibition might be explained by the variation in mutation presence, which was dependent upon the region examined. The heterogeneity demonstrated in these studies provides another phenotypic variant that will impact clinical care.

Surgical management of the patient with papillary cancer.

Papillary cancer is the most common thyroid cancer occurring in all age groups and is usually an indolent tumor, and patients have an excellent prognosis. The majority of patients with papillary cancer do well. It is for the small number of patients who do poorly that it is critical to carry out the appropriate initial operation. The recognized primary treatment of papillary cancer is surgical excision, and the controversy regarding lobectomy versus total thyroidectomy continues. We favor total thyroidectomy because it eradicates multicentric disease, facilitates postoperative radioactive iodine ablation, and allows thyroglobulin levels to be used as a tumor marker for follow-up. Total thyroidectomy should be done by an experienced surgeon to decrease morbidity. Otherwise a total lobectomy on the side of the nodule with subtotal removal on the opposite side is preferred to avoid serious postoperative complications.

[Male urogenital amicrobial phlogosis: effects of the treatment with amtolmetin guacyl on some sperm parameters]. / Flogosi uro-genitali amicrobiche maschili: efficacia del trattamento con amtolmetina guacil su alcuni parametri spermatici.

To examine if some inflammation-related sperm abnormalities were influenced by leucocytospermia (sWBC) alone, WBC-specific Radical oxygen species (WBC-ROS) over-production, and/or by different infected sexual gland sites and if these abnormalities were possibly reversible following treatment with an antiphlogistic drug, a total of 43 infertile male patients with amicrobial male accessory gland infections (MAGI) associated with prostatitis (P, n = 16), prostato-vesiculitis (PV, n = 14) or prostato-vesiculo-epididymitis (PVE, n = 13) as confirmed by ultrasound, were studied. The patients were then further subdivided into two subsets: one of the subsets (P, n = 10; PV, n = 8; PVE, n = 7) was administered amtolmetina guacyl (Eufans) 600 mg once daily for 14 consecutive days per month, for a 2-months period. The second subset (six patients for each category) received no treatment (matched-control). Mean outcome measures included a follow-up of sperm analysis with assessment of sperm forward motility (M), sperm viability (V). In addition, sWBC as well as basal and maximal fMLP-mediated WBC-ROS production were also carried out by conventional immunocytochemistry staining and chemiluminescence analysis respectively. In the pre-treatment, in all patients (treated and not treated subsets) median values of the sperm M and V were significantly different among categories (P > PV > PVE), and necrozoospermia (sperm viability < 25%) were present in the 70% out of group P patients and in all (100%) patients from groups PV and PVE. Median sWBC concentrations, elevated (values > 1 mil/ml) in all groups, in the PV and PVE groups were significantly higher compared to those found in the group P. Furthermore, PVE group generated baseline and fMLP-stimulated ROS productions from low density 45% Percoll fraction (Pc45), significantly higher than those found in P or PV groups. Sperm outcome measures were significantly different compared with the matched-controls (exhibiting 0% case-responders), in a time- and infected gland site-dependent manner. Thus, either in terms of median values and percentages of responders (defined as parameters ensued within the conventional normal range) sperm M and V percentages, as well as sWBC improved after the first (T1) antiphlogistic course in the group P only, but after the second (T2) antiphlogistic course in the other groups (PV or PVE). Moreover, treated patients of each group had amounts of generated basal and fMLP-stimulated ROS signals significantly reduced, with values ensued within a fertile control range at T2, in 80, 62.5 and 42.8% out of the P, PV and PVE groups respectively. We concluded that long-term amtolmetina-guacyl administration demonstrated efficacy and safety in the treatment of amicrobial MAGI, exhibiting a positive impact on all sperm parameters studied and no side-effects.

The use of polyelectrolytes as osmotic agents for peritoneal dialysis.

Various small and large molecules have been studied as osmotic agents to replace dextrose in peritoneal dialysis. Macromolecules are attractive because of their slow absorption from intraperitoneal solutions; however, it has been assumed that they are only marginally effective as osmotic agents unless they function as polyelectrolytes at physiological pH. In experimental exchanges conducted in rats we measured volume changes induced by Gelifundol (5.5% oxypolygelatin) and Ringers lactate to which was added either nothing, 4.25% dextrose, or 5% albumin. In the control exchanges using Ringers lactate, intraperitoneal fluid volume remained unchanged for eight hours. The volume changes induced by 4.25% dextrose were complete within two hours and resulted in a two-thirds increase over the amount of fluid administered. In both series in which polyelectrolytes were used volume transport was sustained throughout an eight hour dwell. With 5% albumin the total increase in fluid volume was about 40% of that installed, while Gelifundol caused fluid volume to double. Qualitatively similar results were obtained in transport studies conducted in vitro. Physical studies of the oxypolygelatin solutions indicated that the fixed charges per liter were comparable to those in the albumin solutions. Thus the different volume transport the two proteins induced could not be attributed to Donnan effects. However, since the molecular weight of albumin is triple that of Gelifundol the van't Hoff pressures of the two macromolecules can explain the observed differences in volume transport. These results suggest that neutral macromolecules deserve further study as potential osmotic agents for peritoneal dialysis.