HE4 Expression in Plasma Correlates with Surgical Outcome and Overall Survival in Patients with First Ovarian Cancer Relapse

Background

Epithelial ovarian cancer (EOC) remains the main cause of mortality due to gynecological malignancies. Optimal tumor debulking and platinum response are the most important prognostic factors for overall survival (OS) in primary EOC. In the setting of recurrence, the role of cytoreduction is not clear. A critical point is to predict preoperatively the subgroup of patients with optimal surgical outcome. The aim of the study was to analyze the predictive role of HE4 for surgical outcome and platinum response in EOC patients experiencing a first relapse. Secondary aims were the prognostic role of HE4 for OS and progression-free survival (PFS).

Methods

Plasma was obtained before secondary cytoreduction from 73 EOC patients. A total of 66.7 % underwent a total macroscopic tumor clearance; 86.3 % of the patients had disease that responded to platinum therapy. HE4 was detected by enzyme-linked immunosorbent assay. For statistical analysis, the chi-square test, Fisher’s exact test, Kendall’s tau b, and Mann-Whitney U test were used. OS, PFS rates, and respective 95 % confidence intervals (CI) were estimated according to the Kaplan–Meier method.

Results

At a HE4 cutoff value of 250 pMk, a sensitivity of 52 % and a specificity of 93.8 % (p = 0.001, 95 % CI 0.601–0.861) were reached in predicting total macroscopic tumor clearance. Plasma HE4 concentrations together with platinum response were the only independent prognostic factors for OS (p < 0.001, hazard ratio [HR] 18.77, 95 % CI 4.68–75.25; and p = 0.044, HR 3.33, 95 % CI 1.03–10.7, respectively). Together with ascites, HE4 was the only independent predictive factor for surgical outcome (p = 0.029, odds ratio [OR] 7.2, 95 % CI 1.22–42.19 and p = 0.036, OR 10.18, 95 % CI 1.16–88.69, respectively).

Conclusions

HE4 is an independent predictive marker for surgical outcome and OS in patients with recurrent EOC. Larger population studies are needed to validate these results.     

Surgical treatment of giant liver hydatid cysts: comparison of cystojejunostomy and partial cystectomy

Purpose

The aim of this study was to compare partial cystectomy and internal drainage of the cyst cavity with cystojejunostomy for the surgical treatment of giant hepatic hydatid cysts.

Methods

Patients who underwent any type of surgical treatment between March 2009 and May 2013 for giant hepatic hydatid cysts were retrospectively evaluated. The data collected included demographic variables, diagnostic methods, surgical procedures, morbidity and mortality rates.

Results

Twenty-eight patients who underwent surgery for giant hepatic hydatid cysts were included. There were 16 (57 %) female patients, with a mean age of 32.8 years. The diagnostic methods primarily included abdominal ultrasonography and computed tomography, which were performed in 62 % of the patients. The patients were divided into two groups with respect to the treatment modality: Group A (n = 13) treated with cystojejunostomy and Group B (n = 15) treated with partial cystectomy. The overall rate of cavity-related complications was 25 % in Group B, whereas none of the patients in Group A had a cavity-related complication during the follow-up period (p < 0.05).

Conclusion

Cystojejunostomy is an effective and safe surgical approach for the treatment of giant hepatic hydatid cysts, with a lower rate of morbidity than partial cystectomy, and thus may be the surgical treatment of choice for giant hepatic hydatid cysts.     

Effectiveness of the Biophysical Barriers to the Peridural Fibrosis in Rat Laminectomy Model

Purpose: Peridural fibrosis which could occur after the spinal surgery could adhere neural tissue closely and may cause to neural entrapment symptoms and require surgical reintervention. Aim of the study: Present study was designed to reduce occurrence of peridural fibrosis in rat laminectomy model by using biophysical barriers called hyaluronic acid (HAS) dural barrier, activated polyethylene glycol and polyethylene imine (PEG) dural barrier, and platelet-rich plasma (PRP). Materials and methods: In this study, 2 of 26 male Wistar albino rats (325–350 g body weight), which were not included into study groups were sacrificed by removing their total blood and their blood was used for preparation of PRP, and remaining rats were randomly delivered into four groups called SHAM, HAS, PEG, and PRP groups. Then L3-4-5 laminectomy was performed to all animals and experimental agents were administered to the selected groups mentioned above. Spinal colons of all animals were removed gross total after 6-week period and investigated histopathologically. Additionally, real-time-polymerase chain reaction was used to obtain collagen type I and type III, transforming growth factor-1β, and tumor necrosis factor-α gene expressions. Results: All results demonstrated that polyethylene glycol and polyethylene imine dural barrier and PRP could decrease peridural fibrosis formation efficiently in rat. Conclusion: Present study results suggested that to reduce or block formation of peridural fibrosis, either polyethylene glycol and polyethylene imine dural barrier or PRP could be used effectively in human subjects after they will be closely investigated in future studies.     

Management of Anemia in Children Receiving Chronic Peritoneal Dialysis

Little information exists regarding the efficacy, modifiers, and outcomes of anemia management in children with CKD or ESRD. We assessed practices, effectors, and outcomes of anemia management in 1394 pediatric patients undergoing peritoneal dialysis (PD) who were prospectively followed in 30 countries. We noted that 25% of patients had hemoglobin levels below target (<10 g/dl or <9.5 g/dl in children older or younger than 2 years, respectively), with significant regional variation; levels were highest in North America and Europe and lowest in Asia and Turkey. Low hemoglobin levels were associated with low urine output, low serum albumin, high parathyroid hormone, high ferritin, and the use of bioincompatible PD fluid. Erythropoiesis-stimulating agents (ESAs) were prescribed to 92% of patients, and neither the type of ESA nor the dosing interval appeared to affect efficacy. The weekly ESA dose inversely correlated with age when scaled to weight but did not correlate with age when normalized to body surface area. ESA sensitivity was positively associated with residual diuresis and serum albumin and inversely associated with serum parathyroid hormone and ferritin. The prevalence of hypertension and left ventricular hypertrophy increased with the degree of anemia. Patient survival was positively associated with achieved hemoglobin and serum albumin and was inversely associated with ESA dose. In conclusion, control of anemia in children receiving long-term PD varies by region. ESA requirements are independent of age when dose is scaled to body surface area, and ESA resistance is associated with inflammation, fluid retention, and hyperparathyroidism. Anemia and high ESA dose requirements independently predict mortality.Almost three decades after the advent of recombinant erythropoietin, the management of renal anemia has become a recent focus of attention and changing paradigms. Whereas correction of hemoglobin (Hb) levels to near-normal has previously been recommended on the basis of association studies linking more severe anemia to morbidity and mortality with dialysis,^1–3 interventional clinical trials consistently demonstrate that near-normalization of Hb increases the risk of vascular events and mortality in adults receiving maintenance hemodialysis and in those with CKD who are not undergoing dialysis.^4–6 This has prompted ongoing reevaluation and revisions of treatment targets in patients exposed to erythropoiesis-stimulating agents (ESAs).⁷The appropriateness of applying treatment recommendations established in adult hemodialysis populations at high cardiovascular risk and adults with CKD to children undergoing dialysis is questionable because cardiovascular events are far less common in children with CKD. Furthermore, two thirds of children requiring dialysis initially opt for peritoneal dialysis (PD), and there are no systematic studies in the adult PD population to inform the optimal Hb target range in these patients. The risk profile of patients receiving PD may differ from that of the hemodialysis setting because of the absence of dialysis-induced intermittent hemoconcentration and lack of contact activation of the complement and coagulation systems.Further aspects to consider in pediatric anemia management are the greater physical activity of children and the need for optimal cognitive functioning at school.^8,9 The significant physiologic variation of the normal Hb range with age¹⁰ and the relative ESA sensitivity that reportedly increases with age during early childhood are also noteworthy.¹¹The registry of the International Pediatric Peritoneal Dialysis Network (IPPN) prospectively collects detailed clinical, biochemical, dialysis, and medication-related information (including ESA types and doses and modalities of iron supplementation) from a substantial number of children undergoing long-term PD around the world. In-depth analysis of this unique database has allowed us to (1) gain insight into the demographic characteristics of renal anemia and its treatment in the pediatric PD population worldwide, (2) explore the relationship between ESA dose requirements and body dimensions, (3) identify factors contributing to ESA resistance in children, and (4) associate anemia control with patient outcomes.     

Effect of Acticoat® and Cutinova Hydro® on wound healing

In this study, the effects of the wound‐covering materials, Acticoat^® and Cutinova Hydro^®, on wound healing have been studied in rabbit models with open and tissue‐lost wounds with full‐thickness flank excisions. Rabbits were used as subjects with three groups of four rabbits each, and trial periods of 7, 14 and 21{\uns}days. Four circular wounds, of 1.5 cm diameter were made two on the right (one of them control) and two on the left (one of them control) of the dorsal sides of the abdomen. Acticoat^® and Cutinova Hydro^® were applied on the wounds with suture for a period of 21 days and one each placed on the right and left sides as control with gauze. Biopsy specimens were taken from the animals at the end of the research period to check the length of the epithelium, epithelial thickness, size of wounds, wound granulation tissue formation and histopathological evaluation for clarity. The Acticoat^® group showed better healing and scar formation compared to the Cutinova Hydro^® group by macroscopic examination. Epithelial wound length and clarity in terms of statistical difference occurred on day 21 (P <0.05); while the length of the wound epithelium decreased patency, epithelial thickness on days~7, 14 and 21, showed no statistical differences (P >0.05). As a result, the Acticoat^® wound dressing was determined as a more reliable for the early wound healing. This study has shown the short‐term clinical benefits of hydroactive, polyurethane dressings in the management of acute wounds. However, longer periods of wound healing procedure should be planned for reliable and safe results of wound dressing. It has also been concluded that microbiological analyses should be included for more robust and reliable comparisons.     

Role of penile electrodermal activity in the evaluation of autonomic innervation of corpus cavernosum

Electrodiagnostic tests measuring the activities of cavernous smooth muscle and sudomotor structures of penile skin are used in order to evaluate autonomic innervation of the penis. Owing to closeness of these tissues, the interference of sympathetic activity during recording is a possibility. In this study, we investigated this possibility in 10 patients whose cavernosal tissues were destroyed during penile prosthesis implantation by comparing the pre- and postoperative penile skin electrodermal activities. Penile electrodermal activities were recorded with surface electrodes before and after the operation. All of the patients had spontaneous and evoked penile electrodermal activity (EDA). The mean amplitude of evoked EDA decreased from 2159+/-700 to 1413+/-515 microV following penile prosthesis surgery (P=0.017). The decrease in the amplitude of penile-evoked EDA following penile prosthesis implantation suggests the contribution of cavernous smooth muscle activity to the sudomotor responses prior to operation. Although corpus cavernosum sympathetic activity contributes to the penile skin recordings, these recordings are mostly the result of penile skin sudomotor sympathetic activity. Therefore, surface potentials recorded from penile skin should not be used for the evaluation of autonomic innervation of corpus cavernosum.     

Comparison of hydraulic and hemolytic properties of different impeller designs of an implantable rotary blood pump by computational fluid dynamics

A mixed-flow blood pump for long-term applications has been developed at the Helmholtz-Institute in Aachen, Germany. Central features of this implantable pump are a centrally integrated motor, a blood-immersed mechanical bearing, magnetic coupling of the impeller, and a shrouded impeller, which allows a relatively wide clearance. The aim of the study was a numerical analysis of hydraulic and hemolytic properties of different impeller design configurations. In vitro testing and numerical simulation techniques (computational fluid dynamics [CFD]) were applied to achieve a comprehensive overview. Pressure-flow charts were experimentally measured in a mock loop in order to validate the CFD data. In vitro hemolysis tests were performed at the main operating point of each impeller design. General flow patterns, pressure-flow charts, secondary flow rates, torque, and axial forces on the impeller were calculated by means of CFD. Furthermore, based on streak line techniques, shear stress (stress loading), exposure times, and volume percentage with critical stress loading have been determined. Comparison of CFD data with pressure head measurements showed excel-lent agreement. Also, impressive trend conformity was observed between in-vitro hemolysis results and numerical data. Comparison of design variations yielded clear trends and results. Design C revealed the best hydraulic and hemolytic properties and was chosen as the final design for the mixed-flow rotary blood pump.     

Does the complication rate increase in laparoscopic cholecystectomy for acute cholecystitis?

BACKGROUND: Laparoscopic cholecystectomy (LC) has replaced open cholecystectomy for the treatment of gallbladder disease. Despite the well-accepted success of LC in chronic cholecystitis, the efficacy of this technique has been subject to some debate in acute cholecystitis (AC). This study was designed to evaluate our institution's experience with LC for AC and chronic symptomatic calculous cholecystitis (CC), based on complication and conversion rates to open surgery. PATIENTS AND METHODS: The records of 1158 patients with LC from September 1991 to December 2001 were analyzed. The parameters of age, gender, early and late complication rates, and conversion rates from LC to open cholecystectomy were compared in patients with AC and CC. RESULTS: During the study period, LC was performed in 1158 patients. Of these, 162 patients had AC (group 1) and 996 patients had CC (group 2). The conversion rates were 4.3% (7/162) in group 1 and 2.4% (24/996) in group 2. The complication rates were not significantly different (5.6% in group 1, 5.1% in group 2, P > 0.05). Difficulty in dissection around Calot's triangle and obscure anatomy were the main reasons for conversion to conventional open surgery. The mortality rate was 1.2% in group 1 and 0.01% in group 2. CONCLUSION: LC appears to be a reliable, safe, and effective treatment modality for AC and CC. The surgical approach should be performed carefully because of the spectrum of potential hazards of the laparoscopic procedure. Conversion and complication rates are similar in both AC and CC groups, and improve as surgeons gain experience.     

Ultrastructural changes in pneumocyte type II cells following traumatic brain injury in rats.

OBJECTIVE: We aimed to demonstrate the time-dependent ultrastructural changes in pneumocyte type II cells following brain injury, and to propose an electron microscopic scoring model for the damage. METHODS: Forty Wistar-Albino female rats weighing 170-200 g were used. The rats were allocated into five groups. The first group was the control and the second was the craniotomy without trauma. The others were trauma groups. Weight-drop method was used for achieving head trauma. Samples were obtained from the right and left pulmonary lobes at 2-, 8-, and 24-h intervals after transcardiac perfusion. An electron microscopic scoring model was used to reveal the changes. RESULTS: There were no ultrastructural pathological findings pointing to lung injury in any rat of the control groups. There was intense intracellular oedema in type II pneumocyte and interstitial oedema in the adjacent tissue in trauma groups. Oedema in mitochondria and dilatation in both smooth endoplasmic reticulum and Golgi apparatus was more evident in the 8- and 24-h trauma groups. The chromatin dispersion was disintegrated in the nucleus in all trauma groups. Scores of all trauma groups were significantly different from the controls (P<0.05). All trauma groups were different from each other at significant levels (P<0.05 for each trauma groups). CONCLUSIONS: The data suggested that ultrastructural damage is obvious at 2 h and deteriorates with time. The electron microscopic scoring model worked well in depicting the traumatic changes, which were supported by lipid peroxidation. Further experiments are needed to determine the exact outcome after brain death model.     

Combined approach for far-lateral lumbar disc herniation

This study evaluated the combination of the classical interlaminar approach and the intertransverse route through a midline approach for the treatment of 18 patients with far-lateral lumbar disc herniations, as identified by magnetic resonance imaging. The patients presented with acute severe sciatica, antalgic posture, positive Lasègue sign and femoral stretch test, motor and sensory deficits, and reflex loss findings. Discectomy of all 18 patients was performed by the combined approach. Neurological outcome of all patients was excellent in the follow-up period, ranging from 5 to 8 years. This combined midline approach permits complete evacuation of the involved disc level and treatment of additional bone resection procedures. Therefore, we advocate this approach in far-lateral lumbar disc herniation cases.