Kidney autotransplantation after nephrectomy and work bench surgery as an ultimate approach to nephron-sparing surgery

Kidney autotransplantation (KAT) is the ultimate approach for nephron-sparing surgery. It is a rarely used method in renal tumor surgery today as minimal invasive and open techniques for nephron-sparing surgery improve constantly. In this publication, the complication rate and the long-term functional and oncological outcome at a single center are analyzed.Methods A prospectively constructed database of patients with renal tumors who underwent renal surgery was retrospectively analyzed to identify patients with KAT and describe surgical and oncological outcomes and to obtain long-term follow-up. Data collection included detailed surgical technique, complications (Clavian-Dindo), and hospital stay, as well as functional and oncological outcome and long-term follow-up.Results Between 1976 and 2013, 12 patients (median age 50.5 years) underwent KAT for highly complex renal masses: in five cases for complex renal cell carcinoma (RCC), five cases for complex upper urinary tract carcinoma (UTUC), one case for a renal metastasis, and one case for nephroblastoma. The nephrectomy or nephron-ureterectomy was performed open via a flank or transabdominal. The median surgical time was 360 min (range 270–490 min). Intraoperatively, six cases required blood transfusions (50%). Six patients (50%) developed significant postoperative complications (Clavian-Dindo > 2). In two patients, intermittent hemodialysis for delayed graft function (16.6%) was needed, and in six cases (50%), additional blood transfusions postoperatively were necessary. At discharge from hospital, all patients had functioning grafts. The median hospital stay was 29.5 days (range 18–35). At follow-up (median follow-up of 83.5 ± 40.7 months), six patients had died (50%)—all with functioning grafts (free from hemodialysis). In five cases, recurrence of primary tumor or metastatic disease was recorded. In four cases, the recurrent carcinoma could be resected; in detail, UTUC in three cases and one partial nephrectomy of the autotransplanted kidney was performed. One patient suffered from bone and lung metastasis. Two patients died finally tumor-related. Five patients (41.6%) are presently alive, without evidence of tumor relapse. One patient developed terminal renal failure requiring hemodialysis 105 months after autotransplantation. One additional patient was lost to follow-up; after 69 months, this patient had a functioning kidney and no evidence of disease-recurrence at the last follow-up. A cumulative number of 1424 months without hemodialysis was gained for these 12 patients. In the literature to date, most KAT are performed in benign disease, with minor but frequent complication. Here, we report the largest series of KAT for malignant kidney tumors. The complication rates are similar, compared to the recently reported series for benign indications with an improved graft survival rate. Since KAT requires a complex and challenging surgical approach, it should be performed by experienced kidney transplant surgeons.Conclusion In very complex cases involving renal tumors and multi-morbidity, patients should be counseled well before KAT is considered. At the same time, KAT should not be abandoned in these very rare cases, especially when a nephron-sparing approach is otherwise not feasible. KAT can maintain renal function and quality of life and extend expectancy of life

Mutational analysis of Polycomb genes in solid tumours identifies <i>PHC3</i> amplification as a possible cancer-driving genetic alteration.

Background: Polycomb group genes (PcGs) are epigenetic effectors implicated in most cancer hallmarks. The mutational status of all PcGs has never been systematically assessed in solid tumours. Methods: We conducted a multi-step analysis on publically available databases and patient samples to identify somatic aberrations of PcGs. Results: Data from more than 1000 cancer patients show for the first time that the PcG member PHC3 is amplified in three epithelial neoplasms (rate: 8–35%). This aberration predicts poorer prognosis in lung and uterine carcinomas (Po0.01). Gene amplification correlates with mRNA overexpression (Po0.01), suggesting a functional role of this aberration. Conclusion: PHC3 amplification may emerge as a biomarker and potential therapeutic target in a relevant fraction of epithelial tumours

MiR-205-driven downregulation of cholesterol biosynthesis through SQLE-inhibition identifies therapeutic vulnerability in aggressive prostate cancer

Prostate cancer (PCa) shows strong dependence on the androgen receptor (AR) pathway. Here, we show that squalene epoxidase (SQLE), an enzyme of the cholesterol biosynthesis pathway, is overexpressed in advanced PCa and its expression correlates with poor survival. SQLE expression is controlled by micro-RNA 205 (miR-205), which is significantly downregulated in advanced PCa. Restoration of miR-205 expression or competitive inhibition of SQLE led to inhibition of de novo cholesterol biosynthesis. Furthermore, SQLE was essential for proliferation of AR-positive PCa cell lines, including abiraterone or enzalutamide resistant derivatives, and blocked transactivation of the AR pathway. Inhibition of SQLE with the FDA approved antifungal drug terbinafine also efficiently blocked orthotopic tumour growth in mice. Finally, terbinafine reduced levels of prostate specific antigen (PSA) in three out of four late-stage PCa patients. These results highlight SQLE as a therapeutic target for the treatment of advanced PCa

Larynxpapillomatose im Kindesalter

Einleitung: Die Larynxpapillomatose ist der häufigste gutartige Tumor des Larynx im Kinderalter. Daher ist bei Heiserkeit, Stridor und Dyspnoe eines Kindes neben einer Laryngomalazie, subglottischer Stenose oder Stimmlippenparese auch die Larynxpapillomatose als eine wichtige Differenzialdiagnose in Betracht zu ziehen.Kasuistik: Wir berichten über den Fall eines 2jährigen Mädchens, bei dem alio loco bei Dysphonie eine Laryngoskopie durchgeführt wurde. Hier zeigte sich intraoperativ der Befund einer ausgeprägten Larynxpapillomatose.Es erfolgte die Verlegung des intubierten Kindes in unsere Klinik. In der Mikrolaryngoskopie zeigte sich die papillomatöse Veränderung auf der linken Seite von der Taschenfalte bis zur Stimmlippe über die vordere Kommissur reichend mit einem rechtsseitigen fast kompletten Befall der Stimmlippe bis zum Sinus Morgagni.Zunächst wurde die rechtsseitige Abtragung des Befundes vollzogen inklusive Stimmlipppenstripping mit Hilfe eines Mikroscherchens. Die sechs Wochen später durchgeführte Kontroll-Mikrolaryngoskopie zeigte eine papillomfreie gut verheilte rechte Seite. Im selben Eingriff wurde die Papillomabtragung links durchgeführt.Bei positivem HPV-6-Status erfolgte eine Vakzinierung.Kontrollmikrolaryngoskopien 6 Wochen sowie 6½ Monate nach der 2.OP zeigen bei guter Stimmfunktion einen unauffälligen Larynxbefund.Schlussfolgerung: Die Abtragung einer ausgedehnten Larynxpapillomatose kann mit Mikroinstrumenten im Kindesalter erfolgen. Die zweizeitige operative Behandlung ermöglicht das Erreichen einer guten Stimmfunktion.Weitere Erfahrungen müssen gewonnen werden, um den Stellenwert einer Vakzinierung bei differenziertem HPV-Nachweis bestimmen zu könne.Der Erstautor gibt keinen Interessenkonflikt an

Larynxpapillomatose im Kindesalter

Einleitung: Die Larynxpapillomatose ist der häufigste gutartige Tumor des Larynx im Kinderalter. Daher ist bei Heiserkeit, Stridor und Dyspnoe eines Kindes neben einer Laryngomalazie, subglottischer Stenose oder Stimmlippenparese auch die Larynxpapillomatose als eine wichtige Differenzialdiagnose in Betracht zu ziehen.Kasuistik: Wir berichten über den Fall eines 2jährigen Mädchens, bei dem alio loco bei Dysphonie eine Laryngoskopie durchgeführt wurde. Hier zeigte sich intraoperativ der Befund einer ausgeprägten Larynxpapillomatose.Es erfolgte die Verlegung des intubierten Kindes in unsere Klinik. In der Mikrolaryngoskopie zeigte sich die papillomatöse Veränderung auf der linken Seite von der Taschenfalte bis zur Stimmlippe über die vordere Kommissur reichend mit einem rechtsseitigen fast kompletten Befall der Stimmlippe bis zum Sinus Morgagni.Zunächst wurde die rechtsseitige Abtragung des Befundes vollzogen inklusive Stimmlipppenstripping mit Hilfe eines Mikroscherchens. Die sechs Wochen später durchgeführte Kontroll-Mikrolaryngoskopie zeigte eine papillomfreie gut verheilte rechte Seite. Im selben Eingriff wurde die Papillomabtragung links durchgeführt.Bei positivem HPV-6-Status erfolgte eine Vakzinierung.Kontrollmikrolaryngoskopien 6 Wochen sowie 6½ Monate nach der 2.OP zeigen bei guter Stimmfunktion einen unauffälligen Larynxbefund.Schlussfolgerung: Die Abtragung einer ausgedehnten Larynxpapillomatose kann mit Mikroinstrumenten im Kindesalter erfolgen. Die zweizeitige operative Behandlung ermöglicht das Erreichen einer guten Stimmfunktion.Weitere Erfahrungen müssen gewonnen werden, um den Stellenwert einer Vakzinierung bei differenziertem HPV-Nachweis bestimmen zu könne.Der Erstautor gibt keinen Interessenkonflikt an

Kidney autotransplantation after nephrectomy and work bench surgery as an ultimate approach to nephron-sparing surgery

Abstract Background Kidney autotransplantation (KAT) is the ultimate approach for nephron-sparing surgery. It is a rarely used method in renal tumor surgery today as minimal invasive and open techniques for nephron-sparing surgery improve constantly. In this publication, the complication rate and the long-term functional and oncological outcome at a single center are analyzed. Methods A prospectively constructed database of patients with renal tumors who underwent renal surgery was retrospectively analyzed to identify patients with KAT and describe surgical and oncological outcomes and to obtain long-term follow-up. Data collection included detailed surgical technique, complications (Clavian-Dindo), and hospital stay, as well as functional and oncological outcome and long-term follow-up. Results Between 1976 and 2013, 12 patients (median age 50.5 years) underwent KAT for highly complex renal masses: in five cases for complex renal cell carcinoma (RCC), five cases for complex upper urinary tract carcinoma (UTUC), one case for a renal metastasis, and one case for nephroblastoma. The nephrectomy or nephron-ureterectomy was performed open via a flank or transabdominal. The median surgical time was 360 min (range 270–490 min). Intraoperatively, six cases required blood transfusions (50%). Six patients (50%) developed significant postoperative complications (Clavian-Dindo > 2). In two patients, intermittent hemodialysis for delayed graft function (16.6%) was needed, and in six cases (50%), additional blood transfusions postoperatively were necessary. At discharge from hospital, all patients had functioning grafts. The median hospital stay was 29.5 days (range 18–35). At follow-up (median follow-up of 83.5 ± 40.7 months), six patients had died (50%)—all with functioning grafts (free from hemodialysis). In five cases, recurrence of primary tumor or metastatic disease was recorded. In four cases, the recurrent carcinoma could be resected; in detail, UTUC in three cases and one partial nephrectomy of the autotransplanted kidney was performed. One patient suffered from bone and lung metastasis. Two patients died finally tumor-related. Five patients (41.6%) are presently alive, without evidence of tumor relapse. One patient developed terminal renal failure requiring hemodialysis 105 months after autotransplantation. One additional patient was lost to follow-up; after 69 months, this patient had a functioning kidney and no evidence of disease-recurrence at the last follow-up. A cumulative number of 1424 months without hemodialysis was gained for these 12 patients. In the literature to date, most KAT are performed in benign disease, with minor but frequent complication. Here, we report the largest series of KAT for malignant kidney tumors. The complication rates are similar, compared to the recently reported series for benign indications with an improved graft survival rate. Since KAT requires a complex and challenging surgical approach, it should be performed by experienced kidney transplant surgeons. Conclusion In very complex cases involving renal tumors and multi-morbidity, patients should be counseled well before KAT is considered. At the same time, KAT should not be abandoned in these very rare cases, especially when a nephron-sparing approach is otherwise not feasible. KAT can maintain renal function and quality of life and extend expectancy of life