Purpose
It is still unclear whether kidney transplantation can be safely performed in patients with prostate cancer after local therapy with curative intent.
Methods
The protocol was registered in ...PROSPERO. We systematically searched Google, MEDLINE, the Cochrane Library, and the ICTRP for studies, official standards, clinical practice guidelines and organ transplant laws. Two review authors independently examined the full-text reports and identified relevant studies and one review author extracted the data. We assessed the overall certainty of the evidence for each outcome according to the GRADE approach.
Results
We identified 1346 references through electronic database searching and finally included 6 references for official standards, clinical practice guidelines, and organ transplant laws, and 6 references for retrospective studies with very low certainty of evidence. We identified no prospective or ongoing studies and reported all results narratively.
Conclusion
We recommend that decisions on kidney transplantation in patients with prostate cancer after local therapy with curative intent should be made on a case-by-case basis. It is indispensable to consult with health care professionals or specialists at transplant centers to obtain individualized information regarding the waiting time requirements for renal transplantation in prostate cancer patients after local therapy with curative intent. No recommendation can be made regarding the waiting times after prostate cancer therapy with curative intent.
The standard treatment for invasive bladder cancer is radical cystectomy. In selected patients, bladder‐sparing therapy can be performed by transurethral resection (TURBT) and radio‐chemotherapy ...(RCT) or radiotherapy (RT). Our published in vitro data suggest that the Neuropilin‐2 (NRP2)/VEGF‐C axis plays a role in therapy resistance. Therefore, we studied the prognostic impact of NRP2 and VEGF‐C in 247 bladder cancer patients (cN0M0) treated with TURBT and RCT (n = 198) or RT (n = 49) and a follow‐up time up to 15 years. A tissue microarray was analyzed by immunohistochemistry. NRP2 expression emerged as a prognostic factor in overall survival (OS; HR: 3.42; 95% CI: 1.48 – 7.86; p = 0.004) and was associated with a 3.85‐fold increased risk of an early cancer specific death (95% CI: 0.91 – 16.24; p = 0.066) in multivariate analyses. Cancer specific survival (CSS) dropped from 166 months to 85 months when NRP2 was highly expressed (p = 0.037). Patients with high VEGF‐C expression have a 2.29‐fold increased risk of shorter CSS (95% CI: 1.03–5.35; p = 0.043) in univariate analysis. CSS dropped from 170 months to 88 months in the case of high VEGF‐C expression (p = 0.041). Additionally, NRP2 and VEGF‐C coexpression is a prognostic marker for OS in multivariate models (HR: 7.54; 95% CI: 1.57–36.23; p = 0.012). Stratification for muscle invasiveness (T1 vs. T2‐T4) confirmed the prognostic role of NRP2 and NRP2/VEGF‐C co‐expression in patients with T2‐T4 but also with high risk T1 disease. In conclusion, immunohistochemistry for NRP2 and VEGF‐C has been determined to predict therapy outcome in bladder cancer patients prior to TURBT and RCT.
What's new?
Neuropilin‐2 (NRP2) and VEGF‐C may play an important role in resistance to treatment. They can induce anti‐apoptotic and autophagic signaling pathways, which protects cancer cells from chemotherapeutic stress in vitro. Therefore, these proteins might be useful as biomarkers for predicting a patient's response to therapy. In this study of bladder cancer patients, the authors demonstrate that NRP2 and VEGF‐C expression are indeed prognostic markers. This may allow more patients to be treated with bladder‐sparing surgery rather than radical cystectomy, and may also be applicable to other types of cancer.
Purpose
Standard androgen deprivation therapy (ADT) can be initiated early at the time of diagnosis in asymptomatic castration-sensitive advanced prostate cancer. This definition has recently been ...expanded to also include an early combined treatment with standard ADT and new antihormonal drugs. We aimed to present the best available evidence for the timing of initiation of ADT monotherapy and combined treatments in castration-sensitive/-resistant prostate cancer.
Methods
For this narrative review, we searched Cochrane reviews in the Cochrane Library, systematic reviews and randomized controlled trials in MEDLINE, phase III and ongoing trials in ClinicalTrials.gov and screened the reference lists to extract articles of interest. One author screened the references which were finally included after assessing their relevance through discussion with other experts in the field.
Results
The identified references were grouped by medication (standard ADT, androgen biosynthesis inhibitor, androgen receptor antagonists or combined therapies) and tumor stage (castration sensitive or resistant). The evidence was narratively summarized and discussed in the context of the current therapeutic landscape.
Conclusions
Early standard ADT can reduce symptoms of disease progression and may extend progression-free and overall survival. The patient should be well informed about the higher rates of treatment-related side effects. Deferring standard ADT might be indicated only for well-informed or unfit patients. Early standard ADT is increasingly combined with new antihormonal drugs in castration-sensitive metastatic prostate cancer to gain additional survival and quality of life benefits. Combined treatment at the time of development of castration-resistant disease is well established.
ZusammenfassungDenkt man an medizinische Forschung, verknüpft man dies intuitiv mit der Analyse von Studiendaten, die speziell für eine Forschungsfrage erhoben wurden oder mit der Sekundärnutzung von ...Patientendaten aus der Routineversorgung. Diese stellen aber mitnichten die einzigen Quellen zur Beantwortung von wissenschaftlichen Fragestellungen dar. Insbesondere für die translationale Forschung liefern auch Gewebe und Flüssigproben wie Blut, DNA oder andere Körperflüssigkeiten essenzielle Erkenntnisse zu Krankheitsentstehung, Entwicklung neuer Therapien und Therapieentscheidungen. Den Zugang zu diesen biomedizinischen Materialien gewährleisten sog. Biobanken. Indem dort humane Bioproben unter Berücksichtigung hoher Qualitätsstandards gesammelt, charakterisiert, dokumentiert und bei Bedarf auch aufbereitet werden, können sie bei der Erforschung von Krankheitsursachen, bei der Früherkennung sowie bei der gezielten Behandlung von Krankheiten unterstützen oder bei der Untersuchung von Volkskrankheiten einen wesentlichen Beitrag leisten.
Congenital megaprepuce is a malformation consisting of a great redundancy of the inner preputial skin over a penis with normal shaft and glans and is combined with a severe phimosis. Patients suffer ...from difficulties in voiding because the urine is trapped in the large dome-shaped megaprepuce. We describe a modification of the surgical technique of reconstructing a megaprepuce initially presented by Leao et al.
We retrospectively reviewed 7 patients aged 6–53 months (mean age 17 months, 6 were younger than 18 months) who underwent congenital megaprepuce repair between 02/2014 and 05/2018 in our institution. All these otherwise healthy children suffering from difficulties in voiding and reporting genital ballooning during micturition and urinary retention were referred to our hospital. In all cases, parents needed to express the trapped urine. Four of these patients additionally showed a glanular hypospadias, another one a distal penile hypospadias. In addition to the repair of the megaprepuce, six patients needed correction of a penile curvature, five of whom needed correction of the chordee and one a corporoplasty (Schröder-Essed). The patient showing the distal penile hypospadias additionally underwent hypospadias repair. During the follow-up, we evaluated the cosmetic result and complications such as secondary concealed penis, difficulties in voiding, urinary retention, and urinary infections.
Mean follow-up was 18 months. All patients following surgery showed normal voiding without urinary retention or urinary infections and good cosmetic results resembling a circumcised penis in appearance without reconcealment. No intraoperative complications occurred. One patient had a scrotal hematoma postoperatively. Mild transient edema of the penis was seen in all patients, which disappeared spontaneously within one week after surgery.
Our surgical approach is a safe and relatively simple procedure with a low rate of complications, good cosmetic results, and functional outcome. Whether the hypospadias associated with ventral curvature was a coincidence or part of the disease pattern remains unclear but will probably be the object of further investigations. Display omitted
Purpose
Prognostic models are developed to estimate the probability of the occurrence of future outcomes incorporating multiple variables. We aimed to identify and summarize existing multivariable ...prognostic models developed for predicting overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC).
Methods
The protocol was prospectively registered (CRD42017064448). We systematically searched Medline and reference lists up to May 2018 and included experimental and observational studies, which developed and/or internally validated prognostic models for mCRPC patients and were further externally validated or updated. The outcome of interest was overall survival. Two authors independently performed literature screening and quality assessment.
Results
We included 12 studies that developed models including 8750 patients aged 42–95 years. Models included 4–11 predictor variables, mostly hemoglobin, baseline PSA, alkaline phosphatase, performance status, and lactate dehydrogenase. Very few incorporated Gleason score. Two models included predictors related to docetaxel and mitoxantrone treatments. Model performance after internal validation showed similar discrimination power ranging from 0.62 to 0.73. Overall survival models were mainly constructed as nomograms or risk groups/score. Two models obtained an overall judgment of low risk of bias.
Conclusions
Most models were not suitable for clinical use due to methodological shortcomings and lack of external validation. Further external validation and/or model updating is required to increase prognostic accuracy and clinical applicability prior to their incorporation in clinical practice as a useful tool in patient management.
Besides the conventional clear-cell renal cell carcinoma (ccRCC), papillary RCC (pRCC) is the second most common renal malignancy. Papillary RCCs can further be subdivided into two distinct subtypes. ...Although a clinical relevance of pRCC subtyping has been shown, little is known about the molecular characteristics of both pRCC subtypes.
We performed microarray-based microRNA (miRNA) expression profiling of primary ccRCC and pRCC cases. A subset of miRNAs was identified and used to establish a classification model for ccRCC, pRCC types 1 and 2 and normal tissue. Furthermore, we performed gene set enrichment analysis with the predicted miRNA target genes.
Only five miRNAs (miR-145, -200c, -210, -502-3p and let-7c) were sufficient to identify the samples with high accuracy. In a collection of 111 tissue samples, 73.9% were classified correctly. An enrichment of miRNA target genes in the family of multidrug-resistance proteins was noted in all tumours. Several components of the Jak-STAT signalling pathway might be targets for miRNAs that define pRCC tumour subtypes.
MicroRNAs are able to accurately classify RCC samples. Deregulated miRNAs might contribute to the high chemotherapy resistance of RCC. Furthermore, our results indicate that pRCC type 2 tumours could be dependent on oncogenic MYC signalling.
Background
The incidence of lymphatic complications after kidney transplantation varies considerably in the literature. This is partly because a universally accepted definition has not been ...established. This study aimed to propose an acceptable definition and severity grading system for lymphatic complications based on their management strategy.
Methods
Relevant literature published in MEDLINE and Web of Science was searched systematically. A consensus for definition and a severity grading was then sought between 20 high‐volume transplant centres.
Results
Lymphorrhoea/lymphocele was defined in 32 of 87 included studies. Sixty‐three articles explained how lymphatic complications were managed, but none graded their severity. The proposed definition of lymphorrhoea was leakage of more than 50 ml fluid (not urine, blood or pus) per day from the drain, or the drain site after removal of the drain, for more than 1 week after kidney transplantation. The proposed definition of lymphocele was a fluid collection of any size near to the transplanted kidney, after urinoma, haematoma and abscess have been excluded. Grade A lymphatic complications have a minor and/or non‐invasive impact on the clinical management of the patient; grade B complications require non‐surgical intervention; and grade C complications require invasive surgical intervention.
Conclusion
A clear definition and severity grading for lymphatic complications after kidney transplantation was agreed. The proposed definitions should allow better comparisons between studies.
Antecedentes
La incidencia de complicaciones linfáticas tras el trasplante renal (post‐kidney‐transplantation lymphatic, PKTL) varía considerablemente en la literatura. Esto se debe en parte a que no se ha establecido una definición universalmente aceptada. Este estudio tuvo como objetivo proponer una definición aceptable para las complicaciones PKTL y un sistema de clasificación de la gravedad basado en la estrategia de tratamiento.
Métodos
Se realizó una búsqueda sistemática de la literatura relevante en MEDLINE y Web of Science. Se logró un consenso para la definición y la clasificación de gravedad de las PKTL entre veinte centros de trasplante de alto volumen.
Resultados
En 32 de los 87 estudios incluidos se definía la linforrea/linfocele. Sesenta y tres artículos describían como se trataban las PKTL, pero ninguno calificó la gravedad de las mismas. La definición propuesta para la linforrea fue la de un débito diario superior a 50 ml de líquido (no orina, sangre o pus) a través del drenaje o del orificio cutáneo tras su retirada, más allá del 7º día postoperatorio del trasplante renal. La definición propuesta para linfocele fue la de una colección de líquido de tamaño variable adyacente al riñón trasplantado, tras haber descartado un urinoma, hematoma o absceso. Las PKTL de grado A fueron aquellas con escaso impacto o que no requirieron tratamiento invasivo; las PKTL de grado B fueron aquellas que precisaron intervención no quirúrgica y las PKTL de grado C aquellas en que fue necesaria la reintervención quirúrgica.
Conclusión
Se propone una definición clara y una clasificación de gravedad basada en la estrategia de tratamiento de las PKTLs. La definición propuesta y el sistema de calificación en 3 grados son razonables, sencillos y fáciles de comprender, y servirán para estandarizar los resultados de las PKTL y facilitar las comparaciones entre los diferentes estudios.
A clear definition and severity grading for lymphatic complications after kidney transplantation is proposed based on the management strategy. The proposed definition and three‐level grading system are generally reasonable, not complicated, and easy to understand; they will allow standardization of results relating to lymphatic complications after kidney transplantation and better comparisons between studies.
Valuable consensus
Purpose of this study was to evaluate prognostic impact of rare variants of urothelial bladder cancer (BC) after treatment with combined radiochemotherapy (RCT). To this end tumour tissue of 238 ...patients with urothelial carcinoma (UC) treated with transurethral resection of the bladder (TUR-B) and RCT with curative intent was collected. Histomorphological analysis included re-evaluation and semi-quantitative assessment of rare UC subtypes. Additionally, human epidermal growth factor receptor 2 (
HER2
) chromogenic in situ hybridisation (CISH) was performed in tumours with a micropapillary component exceeding 30 %. Long-term follow-up was available for 200 patients (range 3–282 months). Variant UC histology was found in 45 of 238 tumours, most frequently micropapillary UC (
N
= 17) including cases with a small fraction of tumour with micropapillary morphology. The mere presence of micropapillary morphology did not affect prognosis. In tumours with extensive (≥30 %) micropapillary morphology (
N
= 8) Kaplan-Meier analysis revealed significantly worse cancer specific survival (CSS) (
P
= 0.002) compared to conventional UC (mean survival times 97 months and 229 months, respectively). Univariate Cox regression analysis of cases with ≥30 % micropapillary morphology revealed a hazard ratio of 4.726 (95 % CI 1.629–13.714) for CSS (
P
= 0.004). CISH revealed
HER2
gene amplification in 3/10 tumours with ≥30 % micropapillary component. In conclusion, for BC treated with TUR-B and RCT, the presence of micropapillary morphology in more than 30 % of the tumour is an adverse prognostic factor. Further studies are needed to evaluate a potential benefit of different, especially multimodal treatment strategies for micropapillary UC and also other subtypes of UC. Her2 represents a promising therapeutic target in a subset of micropapillary UC.
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