How to read a next-generation sequencing report-what oncologists need to know.

Next-generation sequencing (NGS) of tumor cell-derived DNA/RNA to screen for targetable genomic alterations is now widely available and has become part of routine practice in oncology. NGS testing strategies depend on cancer type, disease stage and the impact of results on treatment selection. The European Society for Medical Oncology (ESMO) has recently published recommendations for the use of NGS in patients with advanced cancer. We complement the ESMO recommendations with a practical review of how oncologists should read and interpret NGS reports. A concise and straightforward NGS report contains details of the tumor sample, the technology used and highlights not only the most important and potentially actionable results, but also other pathogenic alterations detected. Variants of unknown significance should also be listed. Interpretation of NGS reports should be a joint effort between molecular pathologists, tumor biologists and clinicians. Rather than relying and acting on the information provided by the NGS report, oncologists need to obtain a basic level of understanding to read and interpret NGS results. Comprehensive annotated databases are available for clinicians to review the information detailed in the NGS report. Molecular tumor boards do not only stimulate debate and exchange, but may also help to interpret challenging reports and to ensure continuing medical education.

Integrated functional and spatial profiling of tumour immune responses induced by immunotherapy: the iPROFILER platform.

BACKGROUND: Cancer immunotherapy elicits functional activation and changes in immune cell distribution in cancer. Tumour heterogeneity is a reason for treatment failure but is difficult to capture in experimental settings. This proof-of-principle study describes the integrated functional and digital spatial profiling platform iPROFILER to capture in-situ immune activation patterns with high precision. MATERIALS AND METHODS: iPROFILER combines an algorithm-based image analysis approach for spatial profiling with functional analyses of patient-derived tumour fragments (PDTFs). This study utilized a folate receptor 1 (FOLR1)xCD3 bispecific antibody in dual-affinity re-targeting (DART) format as a tool for inducing T-cell responses in patient tumour samples, and an in-depth investigation of the immune perturbations induced in the tumour microenvironment was performed. RESULTS: Ex-vivo DART stimulation induces upregulation of multiple activation markers in CD4+ and CD8+ T-cell populations and secretion of pro-inflammatory cytokines in FOLR1-positive tumour specimens. This response was reduced or absent in tissue samples that did not express FOLR1. Immunological responses were driven by a strong induction of interferon gamma (IFNγ) and IFNγ-induced chemokines suggestive of activation of cytotoxic or Th1-like T cells. Ex-vivo DART treatment led to a numerical increase in effector T cells and an upregulation of immune activation markers in the tumour microenvironment as captured by digital image analysis. Analysis of immune activation in tumour and stromal regions further supported the potential of the platform to measure local differences in cell-type-specific activation patterns. CONCLUSIONS: iPROFILER effectively combines functional and spatial readouts to investigate immune responses ex vivo in human tumour samples.

Simulation of Legionnaires' disease prospective spatiotemporal cluster detection, Allegheny County, Pennsylvania, USA.

Legionnaires' disease (LD) incidence in the USA has quadrupled since 2000. Health departments must detect LD outbreaks quickly to identify and remediate sources. We tested the performance of a system to prospectively detect simulated LD outbreaks in Allegheny County, Pennsylvania, USA. We generated three simulated LD outbreaks based on published outbreaks. After verifying no significant clusters existed in surveillance data during 2014-2016, we embedded simulated outbreak-associated cases into 2016, assigning simulated residences and report dates. We mimicked daily analyses in 2016 using the prospective space-time permutation scan statistic to detect clusters of ⩽30 and ⩽180 days using 365-day and 730-day baseline periods, respectively. We used recurrence interval (RI) thresholds of ⩾20, ⩾100 and ⩾365 days to define significant signals. We calculated sensitivity, specificity and positive and negative predictive values for daily analyses, separately for each embedded outbreak. Two large, simulated cooling tower-associated outbreaks were detected. As the RI threshold was increased, sensitivity and negative predictive value decreased, while positive predictive value and specificity increased. A small, simulated potable water-associated outbreak was not detected. Use of a RI threshold of ⩾100 days minimised time-to-detection while maximizing positive predictive value. Health departments should consider using this system to detect community-acquired LD outbreaks.

[Thromboelastography and classical coagulation tests in the preoperative period of liver transplantation]. / Comparación preoperatoria entre pruebas de coagulación y tromboelastografía en pacientes con cirrosis hepática sometidos a trasplante hepático.

BACKGROUND: Compared to standard coagulation essays (SCE), such as international normalized ratio (INR), prothrombin activated partial thromboplastin time (aPTT), or platelet count, thromboelastograhy (TEG) offers precise and real-time information about hemostasis. TEG tests both platelet function and coagulation by assaying several parameters of clot formation dynamically in whole blood. AIM: To evaluate hemostasis in cirrhotic patients undergoing liver transplantation and determine the positive and negative predictive values of SCE for alterations of TEG. MATERIAL AND METHODS: Preoperative SCE and TEG were prospectively analyzed in 25 patients. Results were categorized as normal, laboratory alteration or clinical alteration. SCE results were compared with TEG parameters to determine positive (PPV) and negative predictive values (NPV). RESULTS: Hemostasis was abnormal and laboratory abnormalities were observed in all patients. One patient had clinical signs of excessive bleeding. SCE were abnormal in all patients and TEG was normal in nine patients. The most common alteration in TEG was hypocoagulability, in some cases associated with hypercoagulability and hyperfibrinolysis. Two patients had solely hypercoagulability. PPV of INR, aPTT, platelet count and fibrinogenemia were 0, 0, 0.5 and 0.17 respectively. NPV of the same tests were 1, 1, 0.34 and 1 respectively. CONCLUSIONS: Hypocoagulability was the most common laboratory alteration, however, clinical signs of coagulopathy were rarely present. SCE had a poor predictive value to diagnose o discard hemostatic abnormalities.

Comparación preoperatoria entre pruebas de coagulación y tromboelastografía en pacientes con cirrosis hepática sometidos a trasplante hepático / Thromboelastography and classical coagulation tests in the preoperative period of liver transplantation

Background: Compared to standard coagulation essays (SCE), such as international normalized ratio (INR), prothrombin activated partial thromboplastin time (aPTT), or platelet count, thromboelastograhy (TEG) offers precise and real-time information about hemostasis. TEG tests both platelet function and coagulation by assaying several parameters of clot formation dynamically in whole blood. Aim: To evaluate hemostasis in cirrhotic patients undergoing liver transplantation and determine the positive and negative predictive values of SCE for alterations of TEG. Material and Methods: Preoperative SCE and TEG were prospectively analyzed in 25 patients. Results were categorized as normal, laboratory alteration or clinical alteration. SCE results were compared with TEG parameters to determine positive (PPV) and negative predictive values (NPV). Results: Hemostasis was abnormal and laboratory abnormalities were observed in all patients. One patient had clinical signs of excessive bleeding. SCE were abnormal in all patients and TEG was normal in nine patients. The most common alteration in TEG was hypocoagulability, in some cases associated with hypercoagulability and hyperfibrinolysis. Two patients had solely hypercoagulability. PPV of INR, aPTT, platelet count and fibrinogenemia were 0, 0, 0.5 and 0.17 respectively. NPV of the same tests were 1, 1, 0.34 and 1 respectively. Conclusions: Hypocoagulability was the most common laboratory alteration, however, clinical signs of coagulopathy were rarely present. SCE had a poor predictive value to diagnose o discard hemostatic abnormalities.

Disminución de la presión venosa central: efecto sobre el gasto cardíaco / Reduction of central venous pressure: effect on cardiac output

Introducción: La disminución de la presión venosa central (PVC) a menos de 5mmHg ha sido recomendada para disminuir el sangrado durante la cirugía hepática. No se conoce el efecto de esto en el llenado ventricular e índice cardíaco (IC). Objetivo: Medir el efecto en el volumen de fin de diástole del ventrículo izquierdo indexado (VFDVII) e IC de la disminución a 3-4mmHg de la PVC. Método: Se estudiaron pacientes sometidos a cirugía general en los cuales se monitorizó presión arterial directa, PVC, y ecocardiografía transesofágica (ETE). Posterior a la inducción anestésica, y después de 5min de estabilidad hemodinámica, se midieron VFDVII e IC, los cuales se repitieron 5 min después de disminuir la PVC a 3-4 mmHg. Resultados: Se estudiaron 32 pacientes; 12 cumplían criterios de disfunción diastólica (DD). Los valores basales y posteriores a la reducción de la PVC de VFDVII e IC fueron respectivamente 49,4 ± 13 y 40,1 ±13 ml/m², y 2,8 ± 0,56 y 2,5 ± 0,7 l/m² (ambos p < 0,01). Todas las variaciones fueron mayores en los pacientes con DD. Conclusiones: La disminución de la PVC a los niveles recomendados para disminuir el sangrado produce una moderada pero significativa reducción del IC. Esto debe ser considerado en pacientes con condiciones que pudieran hacer más importante el efecto de la disminución de la PVC.

Introduction: The reduction of central venous pressure (CVP) below 5mmHg has been recommended to decrease bleeding during hepatic surgery. The effect of this practice on cardiac function has not been quantified. Objective: To measure the repercussion of the decrease of CVP on left ventricular end diastolic volume (LVEDV) and cardiac index (CI). Method: Patients undergoing general anaesthesia for major surgery were studied. Monitoring included direct arterial pressure, CVP, and transesophageal echocardiography (TEE). During a stable period of anaesthesia, all of these parameters were measured before and after lowering CVP to 3-4mmHg. Results: Thirty-two patients were studied. Twelve patients met TEE diagnostic criteria for diastolic dysfunction (DD). Basal and post CVP reduction values of LVEDVI and CI were 49.4 ± 13 and 40.1 ±13ml/m², 2.8±0.56 and 2.5±0.7l/m² respectively (both P< .01). All these variations were greater in patients with DD. Conclusions: Reduction of CVP produced a moderate but significant decrease in LVEDV and CI This should be considered in patients with conditions that may increase the effect of decreasing the CVP.

[The pathology of adverse events with immune checkpoint inhibitors]. / Pathologie der Nebenwirkungen von Immune-Checkpoint-Inhibitoren.

BACKGROUND: Immunotherapy has gained importance with the development of new effective cancer treatments. Immune checkpoint inhibitors (ICI) are monoclonal antibodies that promote T­cell mediated tumor immune rejection. Checkpoint blockade also carries the risk of inducing autoimmune reactions ("immune related adverse events", irAEs). The diagnosis and classification of irAEs constitute a new and important field in pathology. AIM: Practice-oriented review of the diagnosis and classification of irAEs. MATERIALS AND METHODS: Structured, selective literature review based on PubMed und UpToDate ® online. RESULTS: The most common irAEs affect the skin, the gastrointestinal tract, the liver, and the respiratory system. The correct diagnosis and classification of irAEs by an interdisciplinary care team is essential for appropriate therapy and the prevention of long-term sequelae. Other important irAEs affect the endocrine organs, the heart, the joints, the kidneys and the nervous system. Because of their rarity and/or limited options for bioptic diagnosis, only limited data on the morphology and pathophysiology of these irAEs are currently available. Autopsies carried out after ICI therapy constitute an important element of quality control and allow better documentation of the incidence and pathogenesis of irAEs. DISCUSSION: Pathology plays a central role in the diagnosis and treatment of irAEs. Future studies may contribute to a better mechanistic understanding of irAEs for individualized knowledge-based risk assessment.

Experiencia clínica con el bloqueador bronquial de ARNDT en pacientes pediátricos / Clinical experience with Arndt bronchial blocker in pediatric patients

Describir la experiencia con el bloqueador bronquial de Arndt (BBA) y determinar los efectos de la ventilación monopulmonar (VMP) en el intercambio gaseoso en pacientes pediátricos. Método: El BBA se utilizó en 11 pacientes que requirieron VMP. Cuando el diámetro del tubo traqueal impedía el uso del BBA como originalmente estaba descrito, éste fue colocado en la tráquea previo a la intubación traqueal quedando por fuera del tubo traqueal. El BBA fue posicionado con ayuda de un fibrobroncoscopio introducido a través del adaptador del bloqueador. Se estandarizaron la modalidad deventilación y las maniobras destinadas a restablecer la oxigenación en caso de desaturación. Se controlaron gases arteriales, presión de vía aérea y CO2 de fin de espiración (EtCO2) ventilando ambos pulmones y en VMP. Resultados: El BBA fue correctamente posicionado en todos los pacientes, obteniéndose un pulmón desinflado en todos ellos. La relación pO2 /FiO2 promedio en decúbito lateral ventilando ambos pulmones y en VMP fue 287 (rango 100-424) y 199 (rango 62-332), p = 0,0108. La diferencia pCO2-EtCO2 mostró un comportamiento variable, aumentando en algunos e incluso haciéndose negativa en otros. Conclusión: El BBA permitió realizar VMP en todos los pacientes. La relación paO2/FiO2 disminuyó en todos los pacientes pero la saturación arterial de oxígeno pudo ser mantenida en niveles seguros. La capnografía mostró ser un indicador poco confiable de la efectividad de la ventilación durante VMP...

Single lung ventilation (SLV) and knowledge of its effects in pediatric patients has been limited by the lack of suitable double lumen tubes (DLT). The bronchial blocker (BB) described by Arndt allows SLV without a DLT, even in small children. Objective: Describe the experience with the Arndt’s BB, and the effects of SLV on gas exchange in children. Design: Observational study. Setting and patients: Eleven children requiring SLV using a BB were studied at a University Hospital. Interventions: A BB was used for SLV. When the internal diameter of the ET didn’t allow the use of the BB as originally described, it was inserted into the trachea before tracheal intubation, leaving the BB next to the ET. A FOB inserted through the multi-portal adapter of the BB guided it to the desired position. Ventilatory pattern and maneuvers to restore arterial oxygen saturation (SatO2) were standardized. Main outcome measures: Arterial blood gases, airway pressure, and EtCO2 were obtained in lateral decubitus position while both lungs were ventilated and during SLV. Results: Ages were between seven months and four years. In 10 patients, the BB was inserted alongside the tracheal tube. In all cases the lung was quiet and deflated. In 2 patients, surgical manipulation dislodged the BB. In one it could not be replaced and thoracotomy was required. Arterial pO2decreased in all patients, but SatO2was maintained above 90%. No significant changes in pCO2 and airway pressure were observed, and pCO2 -EtCO2 relationship was unpredictable. Conclusion: Arndt’s BB allowed SLV in all patients. Even though arterial pO2 decreased in all children, SatO2 could be maintained at an acceptable level...

Updated and expanded study of polycythemia vera and other myeloproliferative neoplasms in the tri-county area.

INTRODUCTION: The results of a 2001-2005 polycythemia vera (PV) investigation in Eastern Pennsylvania revealed a disease cluster plus underreporting and false reporting to the Pennsylvania Cancer Registry (PCR). PURPOSE: The objectives of this study were 1) to assess PV reporting to the PCR in 2006-2009, 2) to determine whether a cancer cluster persisted, and 3) to determine whether other myeloproliferative neoplasms (MPNs), including essential thrombocytopenia (ET), were subject to similar reporting problems. METHODS: Cases were identified from: 1) PCR records from the Tri-County, 2) reviewing billing records at Tri-County hematologist/oncologist offices, and 3) self-identification. An expert panel of physicians reviewed medical records and determined "true," "false," or "indeterminate" cases reported to the PCR. The analyses were conducted to determine sensitivity and positive predictive value (PPV) of case reporting to the PCR, estimate cancer incidence rates, and evaluate the presence of cancer clusters. RESULTS: Of 290 cases identified, 90% were from the original PCR, 9% from billing records, and 1% from self-report. Fifty-five cases consented to participate, and medical records were obtained for 44. The expert panel determined that 45% were true cases, 32% were false cases, and 23% were indeterminate. PV had 100% (95% CI, 59-100) sensitivity, but only 47% PPV (95% CI, 20-70): ET had 78% (95% CI, 47-99) sensitivity and 100% PPV (95% CI, 59-100). Low participation and chart review rates led to rates with wide confidence intervals. We did not identify any PV cancer clusters, but we did identify a cluster of 9 ET cases in the Wilkes-Barre, Pennsylvania area. CONCLUSION: The current study was limited by the low response rate (22%) from MPN patients in the Tri-County area. This study identified 47% PPV for PV reporting and 100% PPV for ET.

"Systolic anterior motion"(SAM): una causa infrecuente de hipotensión severa en el perioperatorio de cirugía no cardiaca / Systolic anterior motion: A report of two cases

Background: Systolic anterior motion describes the anterior displacement of one or both mitral valve leaflets, obstructing the outflow tract of the left ventricle. It can be a cause of severe hypotension during the intraoperative and postoperative period of non-cardiac surgery. The diagnosis is made with echocardiography. We report two patients with this problem. The first was a 74-year-old male subjected to an incisional hernia repair who presented severe hypotension in the intraoperative period. A transesophageal echocardiography revealed an anterior displacement of the mitral valve anterior leaflet. Epinephrine was discontinued and Norepinephrine and a volume expander were administered, with good response. The second patient was a 64-year-old male undergoing a right liver lobectomy. In the postoperative period, he suffered severe hypotension. A transesophageal echocardiography revealed an anterior displacement of the mitral valve anterior leaflet. Dobutamine was discontinued, volume was administered, and a Norepinephrine infusion was started with good response.

[Systolic anterior motion: a report of two cases]. / "Systolic anterior motion"(SAM): una causa infrecuente de hipotensión severa en el perioperatorio de cirugía no cardiaca.

Systolic anterior motion describes the anterior displacement of one or both mitral valve leaflets, obstructing the outflow tract of the left ventricle. It can be a cause of severe hypotension during the intraoperative and postoperative period of non-cardiac surgery. The diagnosis is made with echocardiography. We report two patients with this problem. The first was a 74-year-old male subjected to an incisional hernia repair who presented severe hypotension in the intraoperative period. A transesophageal echocardiography revealed an anterior displacement of the mitral valve anterior leaflet. Epinephrine was discontinued and Norepinephrine and a volume expander were administered, with good response. The second patient was a 64-year-old male undergoing a right liver lobectomy. In the postoperative period, he suffered severe hypotension. A transesophageal echocardiography revealed an anterior displacement of the mitral valve anterior leaflet. Dobutamine was discontinued, volume was administered, and a Norepinephrine infusion was started with good response.

[Trans-esophageal echocardiography in non-cardiac surgery: report of four illustrating cases]. / Casos clínicos: ecocardiografía transesofágica y monitorización hemodinámica en cirugía no cardiaca.

Transesophageal echocardiography can assess ventricular filling ana contraction ana detect motility disturbances secondary to ischemia. In non-cardiac surgery it can be extremely helpful to monitor complex patients. We report a 69-year-old mole subjected to a hepatic lobectomy, a 59-year-old mole with hepatorenal syndrome, a 52-year-old female subjected to a gastric bypass, and a 54-year-old mole subjected to a thyroidectomy. In these four cases, left ventricular motility and preload were evaluated with transesophageal echocardiography, and it was of great aid in decision-making during anesthesia.

Aporte de volumen en el perioperatorio: ¿debemos modificar nuestro enfoque? / Transesophageal echocardiography to monitor fluid administration during the perioperative period

Background: During the perioperative period an adequate intravascular volume must be maintained. Current recommendations overestimate perioperative volume requirements. Aim: To compare perioperative volume administration using standard monitoring methods or guided by left ventricular filling parameters. Material and Methods: Twenty-four patients subjected to colon resection were randomized to monitoring by electrocardiography, blood and central venous pressure, or by transesophageal echocardiography. In the latter, volume administration was adjusted to maintain basal values of left ventricular end diastolic volume and cardiac index. Results: Patients with the standard monitoring system and transesophageal echocardiographic monitoring received 21.1±12 and 6.3 ± 2 ml/kg/h of fluids during the perioperative period, respectively (p < 0.01). Conclusions: The use of transesophageal echocardiography significantly reduced the perioperative fluid administration.

Casos clínicos: ecocardiografía transesofágica y monitorización hemodinámica en cirugía no cardiaca / Trans-esophageal echocardiography in non-cardiac surgery: Report of four illustrating cases

Transesophageal echocardiography can assess ventricular filling ana contraction ana detect motility disturbances secondary to ischemia. In non-cardiac surgery it can be extremely helpful to monitor complexpatients. We report a 69-year-old mole subjected to a hepatic lobectomy, a 59-year-old mole with hepatorenal syndrome, a 52-year-old femóle subjected to a gastric bypass, and a 54-year-old mole subjected to a thyroidectomy. In these four cases, left ventricular motility and preload were evaluated with transesophageal echocardiography, and itwas ofgreat aid in decision-making during anesthesia.

Detection of Merkel cell polyomavirus in epidermodysplasia-verruciformis-associated skin neoplasms.

BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare genodermatosis that is characterized by susceptibility to infection with specific human papillomavirus (HPV) genotypes. Among polyomaviruses, the novel Merkel cell polyomavirus (MCPyV) has been found in different epithelial skin neoplasias. OBJECTIVE: To examine whether EV is associated with cutaneous MCPyV infection. METHODS: We used MCPyV-specific PCR to study skin neoplasms of 6 congenital EV patients and of 1 patient with acquired EV. RESULTS: In all congenital EV patients, MCPyV DNA was found in carcinomas in situ, in invasive squamous cell carcinomas and in common warts. In 4 of these patients, the MCPyV-positive skin lesions were from different anatomic locations. In addition, 1 immunosuppressed patient suffering from acquired EV harbored MCPyV DNA in 2 common warts. In contrast, 7 normal skin samples tested negative for MCPyV DNA. Only 2 out of 24 carcinomas in situ (8.3%) and 2 out of 30 common warts (6.7%) from immunocompetent individuals were positive for MCPyV DNA. CONCLUSIONS: The strong association of EV-associated skin neoplasms with MCPyV suggests a unique susceptibility of EV patients to infections with MCPyV. Both MCPyV and EV-HPV may act as synergistic oncogenic cofactors in the development of EV-associated skin neoplasms.

[Transesophageal echocardiography to monitor fluid administration during the perioperative period]. / Aporte de volumen en el perioperatorio: ¿debemos modificar nuestro enfoque?

BACKGROUND: During the perioperative period an adequate intravascular volume must be maintained. Current recommendations overestimate perioperative volume requirements. AIM: To compare perioperative volume administration using standard monitoring methods or guided by left ventricular filling parameters. MATERIAL AND METHODS: Twenty-four patients subjected to colon resection were randomized to monitoring by electrocardiography, blood and central venous pressure, or by transesophageal echocardiography. In the latter, volume administration was adjusted to maintain basal values of left ventricular end diastolic volume and cardiac index. RESULTS: Patients with the standard monitoring system and transesophageal echocardiographic monitoring received 21.1 ± 12 and 6.3 ± 2 ml/kg/h of fluids during the perioperative period, respectively (p < 0.01). CONCLUSIONS: The use of transesophageal echocardiography significantly reduced the perioperative fluid administration.

Riesgo perioperatorio en pacientes con cirrosis hepática / Perioperative risk among patients with cirrhosis

Ten percent of cirrhotic patients with severely compromised liver function will require a surgical procedure. This article reviews the surgical risk associated with liver damage and surgery. The most important prognostic factor is the degree of functional impairment of the liver. It is evaluated using the Child-Pugh score, which has limitations that have been partially overcome by the Model for End Stage Liver Disease (MELD) score. Cardiac surgery has the highest risk, while extra-thoracic and extra-abdominal procedures have the lowest risk. The mortality for abdominal surgery fluctuates between 11 and 76 percent. Biliary surgery is associated with frequent complications and mortality, which seem to decrease when the procedures are laparoscopic. There are few series that evaluate risk in Child C patients. In liver resective surgery, liver function impairment and magnitude of the excision determine the risk. A high serum creatinine, cardiac failure and emergency surgery are independent risk factors. Although MELD score is useful to predict surgical risk, decision-making must be based on an individualized evaluation of each patient and careful planning of surgical procedures.

[Perioperative risk among patients with cirrhosis]. / Riesgo perioperatorio en pacientes con cirrosis hepática.

Ten percent of cirrhotic patients with severely compromised liver function will require a surgical procedure. This article reviews the surgical risk associated with liver damage and surgery. The most important prognostic factor is the degree of functional impairment of the liver. It is evaluated using the Child-Pugh score, which has limitations that have been partially overcome by the Model for End Stage Liver Disease (MELD) score. Cardiac surgery has the highest risk, while extra-thoracic and extra-abdominal procedures have the lowest risk. The mortality for abdominal surgery fluctuates between 11 and 76%. Biliary surgery is associated with frequent complications and mortality, which seem to decrease when the procedures are laparoscopic. There are few series that evaluate risk in Child C patients. In liver resective surgery, liver function impairment and magnitude of the excision determine the risk. A high serum creatinine, cardiac failure and emergency surgery are independent risk factors. Although MELD score is useful to predict surgical risk, decision-making must be based on an individualized evaluation of each patient and careful planning of surgical procedures.

[Frequent gene fusion in prostate cancer: clinical applications in diagnosis, prognosis and therapy]. / Eine häufige Genfusion im Prostatakarzinom: Klinische Anwendungsmöglichkeiten für Diagnostik, Prognose und Therapie.

The discovery of TMPRSS2-ETS gene fusions in prostate cancer dramatically changed our view of solid tumors. Unveiling the molecular principles of the fusion illustrates the potential for clinical applications with regard to prognosis, diagnosis and therapy. In this review, we summarize the current knowledge about TMPRSS2-ETS gene fusions and delineate how genetic analysis of fusion positive prostate cancer cases can be used as a prognostic marker in clinical routine. The characteristic morphological features of the gene fusion and its detection in prostate biopsies and in urine make it a promising target to identify aggressive tumors. By increasing our knowledge about fusion positive prostate cancer, we will improve the possibility to offer target specific and individualized therapeutic approaches.