A DWI-based hypoxia model shows robustness in an external prostatectomy cohort.

Introduction: Prostate cancer hypoxia is a negative prognostic biomarker. A promising MRI-based tool to assess hypoxia is the 'Consumption and Supply based Hypoxia' (CSH) model based on diffusion-weighted imaging (DWI). The aim of the study was to validate the association between the CSH hypoxia fraction (HFDWI) with pathological Grade Group (pGG) and pathological T-staging (pTstage) in an external prostatectomy cohort. Methods: Apparent diffusion coefficient (ADC) and fractional blood volume (fBV) maps were assessed from DWI data from 291 prostatectomies and combined by the CSH model. HFDWI was calculated for each lesion after median scaling of ADC and fBV to address differences in acquisition and analysis between centers. The absolute HFDWI values and the associations of HFDWI between pGG < 3 versus ≥ 3, and pTstage = 2 versus = 3 in the Netherlands Cancer Institute (NKI) cohort were compared to the obtained by original cohort (Oslo cohort). Statistical T- and Mann-Whitney tests (p<0.05) were performed. Pearson correlation was determined between HFDWI and individual pGG groups. Results: The HFDWI showed comparable absolute values and similar metric performance as in the original published cohort. Higher HFDWI values were observed for higher pGG (Oslo: 0.27; NKI: 0.24) compared to lower pGG (Oslo: 0.11; NKI: 0.17). Similar results were obtained for pTstage. Furthermore, HFDWI demonstrated a significant positive correlation with pGG groups 1-5 (ρ = 0.41, p<0.001). Conclusion: The CSH model exhibited sufficient robustness in the external cohort, suggesting a plausible reflection of true hypoxia and enabling the use of the HFDWI metric for further research into prostate cancer and hypoxia.

Adjuvant Use of PlasmaJet Device During Cytoreductive Surgery for Advanced-Stage Ovarian Cancer: Results of the PlaComOv-study, a Randomized Controlled Trial in The Netherlands.

OBJECTIVE: Standard surgical treatment of advanced-stage ovarian carcinoma with electrosurgery cannot always result in complete cytoreductive surgery (CRS), especially when many small metastases are found on the mesentery and intestinal surface. We investigated whether adjuvant use of a neutral argon plasma device can help increase the complete cytoreduction rate. PATIENTS AND METHODS: 327 patients with FIGO stage IIIB-IV epithelial ovarian cancer (EOC) who underwent primary or interval CRS were randomized to either surgery with neutral argon plasma (PlasmaJet) (intervention) or without PlasmaJet (control group). The primary outcome was the percentage of complete CRS. The secondary outcomes were duration of surgery, blood loss, number of bowel resections and colostomies, hospitalization, 30-day morbidity, and quality of life (QoL). RESULTS: Complete CRS was achieved in 119 patients (75.8%) in the intervention group and 115 patients (67.6%) in the control group (risk difference (RD) 8.2%, 95% confidence interval (CI) -0.021 to 0.181; P = 0.131). In a per-protocol analysis excluding patients with unresectable disease, complete CRS was obtained in 85.6% in the intervention group and 71.5% in the control group (RD 14.1%, 95% CI 0.042 to 0.235; P = 0.005). Patient-reported QoL at 6 months after surgery differed between groups in favor of PlasmaJet surgery (95% CI 0.455-8.350; P = 0.029). Other secondary outcomes did not differ significantly. CONCLUSIONS: Adjuvant use of PlasmaJet during CRS for advanced-stage ovarian cancer resulted in a significantly higher proportion of complete CRS in patients with resectable disease and higher QoL at 6 months after surgery. (Funded by ZonMw, Trial Register NL62035.078.17.) TRIAL REGISTRATION: Approved by the Medical Ethics Review Board of the Erasmus University Medical Center Rotterdam, the Netherlands, NL62035.078.17 on 20-11-2017. Recruitment started on 30-1-2018.

Evaluation of effectiveness of the PlasmaJet surgical device in the treatment of advanced stage ovarian cancer (PlaComOv-study): study protocol of a randomized controlled trial in the Netherlands.

BACKGROUND: The most important goal for survival benefit of advanced stage ovarian cancer is to surgically remove all visible tumour, because complete cytoreductive surgery (CCS) has been shown to be associated with prolonged survival. In a remarkable number of women, CCS is very challenging. Especially in women with many small metastases on the peritoneum and intestinal surface, conventional CCS with electrosurgery is not able to be "complete" in removing safely all visible tumour. In this randomized controlled trail (RCT) we investigate whether the use of the PlasmaJet Surgical Device increases the rate of CCS, and whether this indeed leads to a longer progression free and overall survival. The main research question is: does the use of the PlasmaJet Surgical Device in surgery for advanced stage ovarian cancer result in an increased number of complete cytoreductive surgeries when compared with conventional surgical techniques. Secondary study objectives are: 30-day morbidity, duration of surgery, blood loss, length of hospitalisation, Quality of Life, disease-free survival, overall survival, percentage colostomy, cost-effectiveness. METHODS: The study design is a multicentre single-blinded superiority RCT in two university and nine non-university hospitals in The Netherlands. Three hundred and thirty women undergoing cytoreductive surgery for advanced stage ovarian carcinoma (FIGO Stage IIIB-IV) will be randomized into two arms: use of the PlasmaJet (intervention group) versus the use of standard surgical instruments combined with electrocoagulation (control group). The primary outcome is the rate of complete cytoreductive surgery in both groups. Secondary study objectives are: 30-day morbidity, duration of surgery, blood loss, length of hospitalisation, Quality of Life, disease-free survival, overall survival, percentage colostomy, cost-effectiveness. Quality of life will be evaluated using validated questionnaires at baseline, at 1 and 6 months after surgery and at 1, 2, 3 and 4 years after surgery. DISCUSSION: We hypothesize the additional value of the use of the PlasmaJet in CCS for advanced stage epithelial ovarian cancer. More knowledge about efficacy, side effects, recurrence rates, cost effectiveness and pathology findings after using the PlasmaJet Device is advocated. This RCT may aid in this void. TRIAL REGISTRATION: Dutch Trial Register NTR6624 . Registered 18 August 2017. Medical Ethical Committee approval number: NL62035.078.17 (Medical Ethical Committee Erasmus Medical Centre Rotterdam).

[A woman with subcutaneous nodules after buttock augmentation]. / Een vrouw met subcutane noduli na bilvergroting.

Volume augmentation of the buttocks with injectable soft-tissue fillers is a cosmetic procedure; delayed adverse effects include the formation of granulomatous inflammatory nodules. We describe a 35-year-old woman with early-stage Hodgkin's lymphoma with multiple nodular subcutaneous densities on CT scans in both gluteal regions. These were the result of frequent injections with human collagen.

Prostate Specific Antigen as a Tumor Marker in Prostate Cancer: Biochemical and Clinical Aspects.

In this chapter the use of prostate specific antigen (PSA) as a tumor marker for prostate cancer is discussed. The chapter provides an overview of biological and clinical aspects of PSA. The main drawback of total PSA (tPSA) is its lack of specificity for prostate cancer which leads to unnecessary biopsies. Moreover, PSA-testing poses a risk of overdiagnosis and subsequent overtreatment. Many PSA-based markers have been developed to improve the performance characteristics of tPSA. As well as different molecular subforms of tPSA, such as proPSA (pPSA) and free PSA (fPSA), and PSA derived kinetics as PSA-velocity (PSAV) and PSA-doubling time (PSADT). The prostate health index (phi), PSA-density (PSAD) and the contribution of non PSA-based markers such as the urinary transcripts of PCA3 and TMPRSS-ERG fusion are also discussed. To enable further risk stratification tumor markers are often combined with clinical data (e.g. outcome of DRE) in so-called nomograms. Currently the role of magnetic resonance imaging (MRI) in the detection and staging of prostate cancer is being explored.

Hernia surgery changes in the Amsterdam region 1994-2001: decrease in operations for recurrent hernia.

Inguinal hernia (IH) surgery has changed substantially in the past decade. Conventional (nonmesh) techniques have largely given way to prostheses. This study's aim was to analyse whether changes in technique used for IH repair influenced the operation rate for recurrence. A retrospective study was performed on all adult males who had undergone IH surgery in the Amsterdam region during the calendar years of 1994, 1996, 1999, and 2001. Data were obtained for 3,649 subjects and included patient demographics, hernia type, and surgical technique. We observed a decrease in the use of conventional techniques and a significant increase (P<0.05) in the use of prosthetic materials. The number of operations performed for recurrent hernia decreased from 19.5% (216/1,108) in 1994, to 16.8% 197/1,170) in 1996, to 14.0% (152/1,088) in 1999, and to 14.1% (40/283) in 2001. When comparing 1999 and 2001 with 1994, there was a significant decrease in operations performed for recurrent hernia (P=0.005). There was also a significant increase in supervision of the surgical resident by a surgeon.

Systematic review of survival after acute mesenteric ischaemia according to disease aetiology.

BACKGROUND: Differentiation of acute mesenteric ischaemia on the basis of aetiology is of great importance because of variation in disease progression, response to treatment and outcome. The aim of this study was to analyse the published data on survival following acute mesenteric ischaemia over the past four decades in relation to disease aetiology and mode of treatment. METHOD: A systematic review of the available literature from 1966 to 2002 was performed. RESULTS: Quantitative analysis of data derived from 45 observational studies containing 3692 patients with acute mesenteric ischaemia showed that the prognosis after acute mesenteric venous thrombosis is better than that following acute arterial mesenteric ischaemia; the prognosis after mesenteric arterial embolism is better than that after arterial thrombosis or non-occlusive ischaemia; the mortality rate following surgical treatment of arterial embolism and venous thrombosis (54.1 and 32.1 per cent respectively) is less than that after surgery for arterial thrombosis and non-occlusive ischaemia (77.4 and 72.7 per cent respectively); and the overall survival after acute mesenteric ischaemia has improved over the past four decades. CONCLUSION: There are large differences in prognosis after acute mesenteric ischaemia depending on aetiology. Surgical treatment of arterial embolism has improved outcome whereas the mortality rate following surgery for arterial thrombosis and non-occlusive ischaemia remains poor.

Inguinal hernia repair in the Amsterdam region 1994-1996.

In the Netherlands, approximately 30,000 inguinal hernia repairs are performed yearly. At least 15% are for recurrence. New procedures are being introduced creating discussion on which technique is the best. Currently it is not possible to choose on evidence alone because of the long follow-up that is needed. In 1996 an inventory was taken of all inguinal hernia repairs that were performed in the Amsterdam region (9 hospitals). These results were compared with the results from a similar study performed in 1994. Major changes in treatment strategy were noted. The Bassini repair was replaced by Shouldice and Lichtenstein techniques. There was a significant increase in the use of prostheses for both primary and recurrent inguinal hernias. There was no significant decrease in the percentage of operations performed for recurrent hernia from 19.5% to 16.8%. However, there was a significant decrease in operations performed for early recurrences (5.1%-3.4%) (p = 0.05). These results suggest that the Shouldice and Lichtenstein repairs may be superior to the Bassini repair in terms of early hernia recurrence.

Increased bioavailability of the food-derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in MRP2-deficient rats.

MRP2 is an apical transporter expressed in hepatocytes and the epithelial cells of the small intestine and kidney proximal tubule. It extrudes organic anions, conjugated compounds, and some uncharged amphipaths. We studied the transport of an abundant food-derived carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in vitro, using an MRP2 transfected epithelial cell line (MDCK II) and intestinal explants from Wistar and MRP2-deficient TR(-) rats in Ussing chambers. In the experiments with the transfected cell line, we could demonstrate more than 3-fold higher transport from basolateral to apical than vice versa, whereas the transport in the parent cell line was equal in both directions. These results were confirmed in studies using isolated pieces of small intestine from Wistar and TR(-) rats in the Ussing chamber. Subsequent in vivo experiments demonstrated that after oral administration, absorption of PhIP was 2-fold higher in the TR(-) rat than in the Wistar rat. Consequently, PhIP tissue levels in several organs (liver, kidney, lung, and colon) were 1.7- to 4-fold higher 48 h after oral administration. MRP2 mediated transport of unchanged PhIP probably involves intracellular GSH, because GSH depletion by BSO-treatment in Wistar rats reduced intestinal secretion in the Ussing chamber to the same level as in TR(-) rats. In accordance, BSO treatment increased oral bioavailability in intact Wistar rats. This study shows for the first time that MRP2-mediated extrusion reduces oral bioavailability of a xenobiotic and protects against an abundant food-derived carcinogen.

Effect of cigarette smoking on gastropharyngeal and gastroesophageal reflux.

Gastropharyngeal reflux appears to be associated with various otolaryngological complaints. Cigarette smoking is known to affect adversely the defense mechanisms against reflux of acid gastric contents into the esophagus. To study the relationship between gastropharyngeal, as well as gastroesophageal, reflux and cigarette smoking, 15 subjects underwent 24-hour double-probe pH monitoring while smoking their daily amount of cigarettes. The percentage of time the pH was below 4 during the smoking period was significantly higher than the percentage of time the pH was below 4 during the nonsmoking period, proximal, at the level of the upper esophageal sphincter, as well as distal, above the lower esophageal sphincter. These findings demonstrate that smoking increases gastropharyngeal and gastroesophageal reflux. Smokers with complaints and disorders caused by reflux should therefore be advised to stop smoking in order to reduce reflux.