Turkish Ministry of Health, 2nd Turkish Medical General Assembly Clinical Oncology Study Group Report.

OBJECTIVE: There is an increase in the incidence of cancer, and consequently in mortality rates, both in the world and in Turkey. The increase in the incidence and mortality rate of cancer are more prominent in our country as well as in other developing countries. The aim of this workshop was to determine the current status on prevention, screening, early diagnosis and treatment of cancer in our country, to identify related shortcomings, specify solutions and to share these with health system operators, and to aid in implementation of these systems. Developments on palliative care were also evaluated. MATERIALS AND METHODS: The current situation in the practice of clinical oncology, related drawbacks, problems encountered during multidisciplinary approach and their solutions were discussed under several sub-headings during a 3-day meeting organized by the Turkish Ministry of Health (Türkiye Cumhuriyeti Saglik Bakanligi-TCSB) with participation of 16 scientists from Turkey and 6 from abroad, and the conclusions were reported. RESULTS: It is expected that the newly established Turkish Health Institutes Association (Türkiye Saglik Enstitüleri Baskanligi-TÜSEB) and the National Cancer Institute (Ulusal Kanser Enstitüsü) will provide a new framework in the field of oncology. The current positive findings include the increase in the number of scientists who carry out successful trials in oncology both in Turkey and abroad, the implementation of the national cancer registry program by the Cancer Control Department and the breast cancer registry program by the Turkish Federation of Breast Diseases Societies (Türkiye Meme Hastaliklari Dernekleri Federasyonu-TMHDF), and introduction of Cancer Early Diagnosis, Screening, and Training Centers (Kanser Erken Tani, Tarama ve Egitim Merkezi-KETEM) for the application of community-based cancer screening programs. In addition to these, obvious shortcomings related to education, implementation, management and research issues were also determined, and policy and project proposals to address these issues were presented. Collaboration with relevant organizations in the implementation of these studies was supported. CONCLUSION: Both the incidence and mortality rates of cancer are increasing in Turkey. The widespread deficiencies in population-based screening and in effective treatment lead to an increase in delay in diagnosis and mortality. Despite improvements in data recording, screening and treatment over the last 10 years, extensive, organized, population-based screening programs and fully equipped early diagnosis and treatment centers are required. Enhancement of basic cancer epidemiologic, translational, genetic and molecular research studies is essential in our country. Improvements on pain treatment and palliative care of patients with chronic and terminal cancer are also required.

Linkage of data from diverse data sources (LDS): a data combination model provides clinical data of corresponding specimens in biobanking information system.

To provide sufficient clinical data for corresponding specimens from diverse databases established before the implementation of biobanks for research purposes with respect to data privacy regulations. For this purpose, we developed a data model called "linkage of data from diverse data sources (LDS)". The data model was developed to merge clinical data from an existing local database with biospecimen repository data in our serum bank for uro-oncology. This concept combines two data models based on XML: the first stores information required to connect multiple data sources and retrieve clinical data, and the second provides a data architecture to acquire clinical and repository data. All data were anonymized and encrypted using the Advanced Encryption Standard. X.509 certificates were applied to secure data access. Furthermore, we tested the feasibility of implementing these models in the information management system for biobanking. The data concept can provide clinical and repository data of biospecimens. Only authorized receivers can access these data. Sensitive and personal data are not accessible by the data receivers. The data receiver cannot backtrack to the individual donor using the data model. The acquired data can be converted into a text file format supported by familiar statistical software. Supplementary tools were implemented to generate and view XML documents based on these data models. This data model provides an effective approach to distribute clinical and repository data from different data sources to enable data analysis compliant with data privacy regulations.

Injury severity and seating position in accidents with German EMS helicopters.

INTRODUCTION: Accident rates and fatality rates for Helicopter Emergency Medical Service (HEMS) missions have been investigated recently, but none of these studies considered the influence of the seating position in the helicopter. The aim of the present descriptive and observational study was to analyze injury severity depending on the seating position during HEMS accidents in Germany. MATERIAL AND METHODS: Data from the German Federal Agency for Flight Accident Investigation was gathered for a period of 40 years (from 1970 to 2009). The seating position in the aircraft during the accident and the resulting injury severity (i.e., 1=no; 2=slight; 3=severe; and 4=fatal) were recorded. Injury severity was compared using the Fisher's exact test. P values <0.05 were considered statistically significant. RESULTS: A total of n=99 accidents were investigated (n=61 accidents did not lead to any injuries in the occupants, n=7 accidents resulted in minor, and n=6 in severe injuries, and lethal injuries resulted from n=15 accidents). The occupant in the "patient" position was most likely to suffer from deadly injuries (44.9%), followed by the HEMS crew member rear seat (25.0%), compared to lower lethality rates in the other seating positions (9.4-11.2%). Sitting on the HEMS crew member rear seat also was associated with the highest percentage of severe and minor injuries (12.5% each). CONCLUSIONS: In HEMS accidents, the patients' position and the HEMS crew member rear seat were found to be at the highest risk for fatal or severe injuries. These results support the urgent requirement of a large international data base for HEMS accidents as a basis for further studies to improve the safety in HEMS missions.

Urodynamic effect of 80 watt photoselective laser vaporization of the prostate.

OBJECTIVE: The aim of the analysis was to measure the pressure-flow urodynamic changes following GreenLight(™) laser vaporization of the prostate based on pressure-flow studies. MATERIAL AND METHODS: Sixty-two patients suffering from voiding dysfunction due to lower urinary tract symptoms underwent potassium titanyl phosphate (KTP) laser vaporization. A pressure-flow study was performed at baseline and at 3 months postoperatively. Symptoms and quality of life (QoL) were assessed using the International Prostate Symptom Score (IPSS) and questions regarding sexuality were assessed using the International Index of Erectile Function (IIEF). RESULTS: IPSS and QoL scores changed from 24 and 5 at baseline to 6 and 2 at 3 months, respectively. The initial median prostate volume was 35 ml (range 16-60 ml), the median maximum uroflow (Q max) was 9.2 ml/s (4-14.9 ml/s) and the median postvoiding residual urine was 80 ml (20-400 ml) (95% confidence interval 89.14, 135.44). The median IPSS and QoL score were significantly improved (p < 0.001). There was a significant decrease in median detrusor pressure at Q max from 83.1 to 40.45 cmH2O, and the median obstruction grade according to Schäfer's classification was also decreased significantly, from 4 to 1 postoperatively. CONCLUSION: This study showed that significant deobstruction can be demonstrated using a pressure-flow study at 3 months postoperatively.

CMDX©-based single source information system for simplified quality management and clinical research in prostate cancer.

BACKGROUND: Histopathological evaluation of prostatectomy specimens is crucial to decision-making and prediction of patient outcomes in prostate cancer (PCa). Topographical information regarding PCa extension and positive surgical margins (PSM) is essential for clinical routines, quality assessment, and research. However, local hospital information systems (HIS) often do not support the documentation of such information. Therefore, we investigated the feasibility of integrating a cMDX-based pathology report including topographical information into the clinical routine with the aims of obtaining data, performing analysis and generating heat maps in a timely manner, while avoiding data redundancy. METHODS: We analyzed the workflow of the histopathological evaluation documentation process. We then developed a concept for a pathology report based on a cMDX data model facilitating the topographical documentation of PCa and PSM; the cMDX SSIS is implemented within the HIS of University Hospital Muenster. We then generated a heat map of PCa extension and PSM using the data. Data quality was assessed by measuring the data completeness of reports for all cases, as well as the source-to-database error. We also conducted a prospective study to compare our proposed method with recent retrospective and paper-based studies according to the time required for data analysis. RESULTS: We identified 30 input fields that were applied to the cMDX-based data model and the electronic report was integrated into the clinical workflow. Between 2010 and 2011, a total of 259 reports were generated with 100% data completeness and a source-to-database error of 10.3 per 10,000 fields. These reports were directly reused for data analysis, and a heat map based on the data was generated. PCa was mostly localized in the peripheral zone of the prostate. The mean relative tumor volume was 16.6%. The most PSM were localized in the apical region of the prostate. In the retrospective study, 1623 paper-based reports were transferred to cMDX reports; this process took 15 ± 2 minutes per report. In a paper-based study, the analysis data preparation required 45 ± 5 minutes per report. CONCLUSIONS: cMDX SSIS can be integrated into the local HIS and provides clinical routine data and timely heat maps for quality assessment and research purposes.

Distribution of EphB4 and EphrinB2 in normal and malignant urogenital tissue.

OBJECTIVE: Ephrin (Eph) receptors are receptor tyrosine kinases; both EphrinB2, as a ligand, and EphB4, as a receptor, are involved in angiogenesis. EphrinB2 is expressed on arteries and EphB4, a specific receptor for EphrinB2, is expressed on veins. It is unknown whether involvement of arteries and veins in tumor angiogenesis is distinctive. Here we investigated their distribution in normal and malignant tissue of the urogenital tract. MATERIALS AND METHODS: Five-micrometer-thick paraffin sections from nontumoral and tumoral tissues of kidney (n = 12), bladder (n = 33), and prostate (n = 20) were immunoreacted with antisera against EphB4 and EphrinB2 using the avidin-biotin-peroxidase complex technique. Comparisons of EphB4 and EphrinB2 stained arterial and venous vessels in the nontumoral and tumoral sections were evaluated in a semiquantitative analysis as frequency of the vessels in a predetermined tumor area counted under light microscopy. RESULTS: Expression of EphrinB2 in arterial and EphB4 in venous endothelium was significantly greater in tumoral sections compared with nontumoral sections. No statistically significant correlation in comparing the labeling patterns for EphrinB2 with the labeling patterns for EphB4 was observed in nontumoral as well as tumoral sections. CONCLUSIONS: The high expression of EphrinB2 in arterial and EphB4 in venous endothelium of urogenital tract tumors might contribute to their involvement in the progression of tumor angiogenesis. The relation between arteries and veins in the normal and tumor tissues is unchanged.

Preoperative chronic pain in radical prostatectomy patients: preliminary evidence for enhanced susceptibility to surgically induced pain.

BACKGROUND AND OBJECTIVE: The aim of the study was to examine a possible relationship between the extent of preoperative chronic pain and the development of moderate-to-severe acute postoperative pain. METHODS: Eighty-four patients scheduled for radical prostatectomy were studied. Pain intensities after mobilization during the first 3 postoperative days were added to yield a total pain score (total pain score after mobilization, range 0-30). Pain was considered as moderate to severe at a total pain score after mobilization of 12 or higher. The preoperative severity of chronic pain disorders was measured using the Mainz Pain Staging System (I-III). Further possible preoperative risk factors for the development of intense postoperative pain that were examined included pain intensity, pain in the urological site, psychological distress (Hospital Anxiety and Depression Scale) and health-related quality of life (Short Form-12). RESULTS: Patients with moderate-to-severe preoperative chronic pain and those with higher Mainz Pain Staging System stages were significantly (P < 0.001) more likely to develop moderate-to-severe postoperative pain. Anxiety and depression scores as well as physical health (Short Form-12) were significantly associated with a total pain score after mobilization of at least 12. The development of postoperative pain was independent of the presence of preoperative pain in the urological site. CONCLUSION: This study demonstrated that higher degrees of preoperative chronic pain were associated with the development of more intense pain after radical prostatectomy. Preoperative psychological distress and reduced physical health were associated with a marked increase in postoperative pain intensity.

Chronic pain and disability after pelvic and acetabular fractures--assessment with the Mainz Pain Staging System.

BACKGROUND: Chronic posttraumatic pelvic pain (PPP) after pelvic ring fractures impacts negatively on quality of life issues. This study aimed to more clearly identify and quantify the problem. METHODS: For this cross-sectional study, patients were examined 52 (median) months after pelvic fractures. The following parameters were measured: pain chronicity (Mainz Pain Staging System [MPSS]), pain intensity (Numeric Rating Scale, 0-10), pelvic fracture outcome scores (Majeed, Pohlemann, and Bürk), pain severity (Chronic Pain Grading Questionnaire), pain-related interference with activities of daily living (Chronic Pain Grading Questionnaire), low back pain-related disability (Oswestry score), neuropathic pain (painDETECT), physical functioning (Short Form-12), and medical comorbidities (Weighted Illness Check List-20). Psychological distress was evaluated for anxiety and depression (Hospital Anxiety and Depression Scale) and mental quality of life (Short Form-12). RESULTS: Sixty-nine patients had a total of 49 pelvic and 41 acetabular fractures; 70% underwent osteosynthesis. The prevalence of PPP was 64%. Prevalence weighted with the dysfunctional pain chronicity stages MPSS II and III was 48%. Patients with pelvic fracture types (AO classification) A, B, and C had PPP prevalences of 38%, 67%, and 90%, respectively. Pain chronicity stages (MPSS) were moderately to strongly correlated with pelvic pain intensity (r = 0.57), the three pelvic fracture outcome scores (r = -0.78 to -0.90), pain-related interference (r = 0.72), Oswestry score (r = 0.68), nerve injury and neuropathic pain (r = 0.52), reduced physical (r = -0.72) and mental functioning (r = -0.58), trauma-related comorbidity (r = 0.53), anxiety (r = 0.51), and depression (r = 0.67). CONCLUSION: This study demonstrated that the intensity and prevalence of PPP are high even some 4 years after injury. The validated instruments MPSS (measuring pain chronicity) and Oswestry disability score proved to be appropriate for classifying outcome after pelvic ring fractures.

[Chronic pain in urology: inguinal pain, post vasectomy pain, and chronic pelvic pain]. / Chronische Schmerzen in der Urologie: Leistenschmerzen, Postvasektomie-Schmerzen und chronische Beckenschmerzen.

Undertreatment of all forms of acute and chronic pain is also present in Germany. Chronic inguinal pain and post vasectomy pain are frequently observed in urological practice and appear as chronic postsurgical pain. Chronic pelvic pain has inflammatory causes in the majority of cases and appears as a challenge for the treating physician. Pain should be treated as early as possible, if necessary also interdisciplinary, with regard to the further chronification process with changes of biological, psychological and social factors. For the patient the pain chronification can be accompanied by the reduction of quality of life and social isolation.

Preoperative pain as a risk factor for chronic post-surgical pain - six month follow-up after radical prostatectomy.

BACKGROUND: Chronic post-surgical pain (CPSP) by definition develops for the first time after surgery and is not related to any preoperative pain. Preoperative pain is assumed to be a major risk factor for CPSP. Prospective studies to endorse this assumption are missing. METHODS: In order to assess the incidence and the risk factors for CPSP multidimensional pain and health characteristics and psychological aspects were studied in patients prior to radical prostatectomy. Follow-up questionnaires were completed three and six months after surgery. RESULTS: CPSP incidences in 84 patients after three and six months were 14.3% and 1.2%. Preoperatively, CPSP patients were assigned to higher pain chronicity stages measured with the Mainz Pain Staging System (MPSS) (p=0.003) and higher pain severity grades (Chronic Pain Grading Questionnaire) (p=0.016) than non-CPSP patients. CPSP patients reported more pain sites (p=0.001), frequent pain in urological body areas (p=0.047), previous occurrence of CPSP (p=0.008), more psychosomatic symptoms (Symptom Check List) (p=0.031), and worse mental functioning (Short Form-12) (p=0.019). Three months after surgery all CPSP patients suffered from moderate to high-risk chronic pain (MPSS stages II and III) compared to 66.7% at baseline and 82.3% had high disability pain (CPGQ grades III and IV) compared to 41.7% before surgery. CPSP patients scored significantly less favorably in physical and mental health, habitual well-being, and psychosomatic dysfunction three months after surgery. CONCLUSIONS: All patients with CPSP reported on preoperative chronic pain. Patients with preoperative pain, related or not related to the surgical site were significantly at risk to develop CPSP. High preoperative pain chronicity stages and pain severity grades were associated with CPSP. CPSP patients reported poorer mental health related quality of life and more severe psychosomatic dysfunction before and 3 months after surgery.

Risk factors for acute and chronic postoperative pain in patients with benign and malignant renal disease after nephrectomy.

AIMS: This longitudinal study was performed in order to analyze the incidence of and perioperative risk factors for the development of chronic postsurgical pain (CPSP) in patients after nephrectomy. METHODS: For baseline data acquisition, valid instruments were used for scoring sociodemographic, psychological, psychosocial, pain, pain treatment, and comorbidity factors: the Mainz Pain Staging System (MPSS) for pain chronicity, the Chronic Pain Grading Questionnaire (CPGQ), the Neuropathic Pain Scale (NPS), the Hospital Anxiety and Depression Scale (HADS), the Short Form 12 (SF-12) for health-related quality of life, the Habitual Well-Being Questionnaire (HWBQ), the Symptom Check List (SCL-8) for detecting psychosomatic dysfunction, and the Weighted Illness Check List (WICL) for evaluation of comorbidities and their impact on activities of daily living. Pain intensities were recorded over the first 6 postoperative days after nephrectomy. A sample of 35 patients was followed up for 3 and 6 months. RESULTS: Patients with more intense postoperative pain during the first 6 days had significantly higher preoperative anxiety scores. The incidence of CPSP 3 and 6 months after nephrectomy was 28.6% and 8.6%, respectively. Preoperatively increased anxiety scores, reduced physical health-related quality of life (SF-12), multiple comorbid conditions, and increased comorbidity-related disability were significantly associated with the occurrence of CPSP after 3 months. These patients also reported more severe pain during the first week after surgery. Preoperative "current pain intensity" was significantly increased in CPSP patients. CONCLUSIONS: Our results demonstrate a multifactorial development of CPSP. This process may contribute not only to the occurrence of chronic postsurgical pain but also to the biopsychosocial impairment in these patients as often seen in other chronic pain populations.

Prevalence, severity, and chronicity of pain and general health-related quality of life in patients with localized prostate cancer.

AIMS: To analyze the prevalence and the severity spectrum of pain and its relationships to health-related quality of life and the bio-psycho-social consequences of pain among patients scheduled for radical prostatectomy. METHODS: Urological inpatients completed an epidemiological pain questionnaire extensively exploring pre-operative acute and chronic pains in 21 body regions. The severity of pain was determined using von Korff's Pain Grading (CPGQ). Pain chronicity was estimated employing the Mainz Pain Staging System (MPSS). Anxiety and depressive symptoms were identified with the HADS and the Habitual Well-Being Questionnaire (FW-7). Health-related quality of life was measured using the SF-12. Comorbidities and comorbidity-related interferences with daily activities were ascertained with the Weighted Illness Checklist (WICL). RESULTS: Eighty of 115 patients (69.6%) reported about pain during the last 3 months pre-operatively. 28.7% of the pain patients had pain related to urological disease. Severe dysfunctional pain was identified by pain Grades 3 and 4 of the CPGQ in 20% and 13.8%, respectively. Advanced pain chronicity characterized by pain Stages II and III of the MPSS was present in 38.8% and 11.3%. Patients with localized prostate cancer without pain complaints had significantly better health-related quality of life and habitual well-being and lower anxiety and depression scores and fewer comorbidities. Patients with cancer-related and non-cancer pain did not differ in pain chronicity, pain severity, pain intensities, anxiety, comorbidities and physical health (SF12-PCS). CONCLUSIONS: The high prevalence of severe and chronic pain in cancer patients before scheduled radical prostatectomy--combined with considerable disability effects and markedly reduced quality of life necessitate a short routine screening-analysis of the severity spectrum of pain and psychopathology. Patient self-rated pain chronicity staging and psychological distress analysis will allow a disorder severity-guided treatment and the prevention of suffering and additional new chronic post-surgical pain.

Detection of circulating tumor cells in patients with renal cell carcinoma by reverse transcriptase polymerase chain reaction for G250/MNCA-9: results of a prospective trial.

OBJECTIVES: Radical nephrectomy displays the standard procedure for patients with localized renal cell carcinoma. The transperitoneal approach is often favored compared to the retroperitoneal approach because of the early ligation of the renal vessels, thereby tumor cell shedding by manipulation of the tumor is thought to be avoided. The aim of our study was to investigate the influence of the surgical technique on intraoperative tumor cell shedding. Furthermore, we evaluated the clinical course of the patients being operated on with either method in terms of complications, postoperative recovery, and hospital stay. METHODS: A total of 55 consecutive patients with renal tumors suspicious for malignancies were evaluated for this study. Peripheral blood samples were obtained from 44 patients at admission, intraoperatively (before and after kidney removal), and before discharge. Ribonucleic acid was extracted, converted to complementary deoxyribonucleic acid, and reverse transcriptase polymerase chain reaction (RT-PCR) with primers specific for G250/MNCA-9 was performed. Data regarding the clinical course of the patients were analyzed retrospectively by reviewing patient files. RESULTS: The clinical course for patients undergoing retroperitoneal nephrectomy was statistically different compared to the transperitoneal approach group regarding operating time and duration of drains, favoring the retroperitoneal approach group. Evaluation of MNCA-9 RT-PCR revealed no difference according to operative technique, tumor-nodes-metastasis, or clinical tumor stage. Despite this result, we found positive RT-PCR signals for MNCA-9 in patients with transitional cell cancer of the renal pelvis and benign renal lesions. CONCLUSIONS: There is no clinical relevant difference between the transperitoneal and retroperitoneal approaches for radical nephrectomy. Furthermore, the retroperitoneal approach does not bear the risk of intraoperative tumor cell shedding by the handling of the tumor.

Vessels in benign prostatic hyperplasia contain more binding sites for endostatin than vessels in normal prostate tissue.

OBJECTIVE: The angiogenic phenotype is an effect of a net balance of angiogenic and anti-angiogenic factors. Endostatin is one of a group of recently described matrix-derived inhibitors of tumour angiogenesis that have acquired increasing significance for tumour treatment. Endostatin's anti-angiogenic mechanism and the causes of its heterogenic influence on various tissue types have not yet been defined. METHODS: We investigated the variations in endostatin's binding behaviour to vessels in benign prostatic hyperplasia (BPH) compared to endostatin binding to vessels in normal prostate tissue. Biotinylated endostatin was used and was detected using Extravidin CY3. RESULTS: In BPH 89.12% +/- 10.72% of vessels showed endostatin binding. This was significantly more than observed for vessels in normal prostate tissue (1.66% +/- 1.66%). CONCLUSION: The strongly proliferative tissue of BPH may be a growth-limited cause of significantly more endostatin binding sites. The investigation indicates endostatin as a possible new target for BPH treatment.

Surgical management of vesicoureteral reflux in pediatric patients.

Vesicoureteral reflux (VUR) represents one of the most significant risk factors for acute pyelonephritis in children. The current indications for the surgical correction of VUR depend on the presence or absence of renal scars. If no scars are present, primary ureteral reimplantation is only indicated in high-grade bilateral VUR, whereas in the presence of renal scars surgical correction is indicated in low/high grade reflux at a young age. Since there are numerous techniques for antireflux surgery available, it is the purpose of this article to critically review these techniques with their specific advantages, typical complications and postoperative management. In general, all surgical technique have a high success rate of 92-98%. The extravesical Lich-Gregoir technique is primarily indicated in unilateral VUR. Children with a high-grade VUR, who are under the age of 3 years and boys are prone to the development of postoperative urinary retention and might be considered for intravesical surgical techniques. The Politano-Leadbetter technique is very helpful in correcting bilateral VUR of any grade in one session to create a neo-ostium in an anatomically correct position which is easily accessible for endourological manipulations. The Psoas hitch ureteroneocystotomy is an excellent technique to correct VUR associated with megaureter, or with duplicated ureters, and VUR failures. Endoscopic subureteral injections are primarily reserved for low grade VUR with a one session success rate of >90%. Endoscopic subureteral injections appear to be an alternative to long-term antibiotics in grade I-III VUR. Laparoscopic antireflux surgery has not gained widespread use due to the very long operating times. Contralateral VUR will occur in about 20% of children undergoing unilateral antireflux surgery; risk factors are severe VUR and VUR into a duplicated system. Postoperative follow-up nowadays consists of urinalysis and ultrasonography; voiding cystourethrography is only indicated in case of febrile urinary tract infection. Despite the excellent success rates following antireflux surgery one has to keep in mind that surgery only corrects the anatomical abnormality. The long-term outcome with regard to renal function, posttherapeutic febrile urinary tract infections and arterial hypertension does not differ significantly from the medication group except for those patients with a demonstrated a genetic background. Therefore, the indication for surgery and the surgical technique applied have to be discussed thoroughly and must be associated with a minimal complication rate.