Effects of Adrenaline on maternal and fetal fentanyl absorption in epidural analgesia: A randomized trial.

BACKGROUND: The combination of low-dose local anesthesia and lipophilic opioids such as fentanyl is established as a standard solution for labor epidural analgesia. Fentanyl increases efficacy, but may have negative effects on the neonate in terms of reduced neonatal neurologic and adaptive capacity scores and breast feeding. We hypothesized that addition of adrenaline 2 µg/mL to a solution of bupivacaine 1 mg/mL and fentanyl 2 µg/mL would reduce the systemic uptake of fentanyl, resulting in reduced serum fentanyl in the fetus at birth. METHODS: Forty-one nulliparous women requesting epidural analgesia were randomized to epidural analgesia with or without adrenaline. Blood samples were drawn from the mother with regular intervals, and at delivery. An umbilical vein blood sample (used as a proxy for fetal exposure) was drawn after clamping. RESULTS: There were no significant differences between the groups in fentanyl concentrations in the umbilical vein and maternal serum at birth. There was a significantly lower mean area under the maternal serum-concentration curve for the first 2 hours of treatment in the adrenaline group (mean difference 0.161 nmol h/L [0.034; 0.289], P = .015), implying slower systemic uptake in the adrenaline group initially. There were no significant differences in treatment duration, motor block, Apgar scores, umbilical pH and base excess, or mode of delivery. CONCLUSIONS: The addition of adrenaline to an epidural solution containing fentanyl lowered maternal systemic serum fentanyl concentration during the first 2 hours, but did not lower serum fentanyl concentration in the umbilical vein and mother at delivery.

[When is surgical resection of metastases in testicular germ cell tumors indicated and is there a scientific basis?] / Wann ist die operative Versorgung von Metastasen beim testikulären Keimzelltumor angezeigt und gibt es eine wissenschaftliche Grundlage dafür?

Surgical resection of metastases represents an integral part of curative management in patients with testicular germ cell tumors (GCT). Primary nerve-sparing retroperitoneal lymph node dissection (nsRPLND) for low volume metastases in clinical stages I-IIB has to be differentiated from the more complex and more extensive postchemotherapeutic procedures. In Europe, primary nerve-sparing retroperitoneal lymph node dissection (nsRPLND) for clinical stage I nonseminomatous GCT (NSGCT) plays a subordinate. In clinical stage IIA/B, nsRPLND is indicated for patients with marker-negative metastases in whom cure rates of about 65% can be achieved with surgery alone. For clinical stage IIA/B seminomas, nsRPLND represents an individual, still experimental procedure with high cure rates. Postchemotherapy residual tumor resection (pRTR) for advanced seminomas is only indicated in the context of a FDG-PET/CT-positive residual mass >3 cm in diameter. For NSGCT, pRTR is indicated in patients with residual masses >1 cm and negative or plateauing tumor markers to resect persisting teratoma or vital cancer. Complete resection of all masses including resection of adjacent vascular, visceral or skeletal metastases is mandatory to achieving the highest cure rate possible. Due to the complexity and the lower rate of significant morbidity and mortality, these procedures should be done at tertiary referral centers.

Surgical management of complex residual masses following systemic chemotherapy for metastatic testicular germ cell tumours.

Background: Post-chemotherapy retroperitoneal lymphadenectomy (PC-RPLND) represents the treatment of choice in patients with residual masses following chemotherapy for metastatic germ cell tumours. Involvement of major retroperitoneal vessels or thoracic/lumbar spine is rare and challenging but needs complete resection for curative intent. We report on our experience in the management of such complex cases. Patients and methods: A total of 185 patients underwent PC-RPLND and we identified 25 (13.5%) patients who needed complex adjunctive vascular (n = 16, 8.6%), skeletal (n = 5, 2.7%) and pancreaticoduodenal (n = 4, 2.2%) surgeries. We performed a retrospective analysis of treatment-associated complications according to the Clavien-Dindo classification. Progression-free, cancer-specific and overall survival was calculated. Results: All patients were of intermediate/poor prognosis according to IGCCCG. Median tumour diameter at time of surgery was 18.6 (9.0-35) cm. Sixteen (8.6%) underwent vascular surgery including aortic resection and replacement, complete or partial resection of the inferior vena cava with thrombectomy, and resection and replacement of the iliac vessels. In five patients, 1-2 metastatic lumbar vertebral bodies were resected, stabilized and replaced. Four patients underwent en-bloc resection of a suprahilar mass with pancreas and duodenum. Pathohistology revealed vital cancer in five patients; teratoma and malignant somatic transformation was identified in 12 and 6 patients, respectively. Complications occurred more often in the group of complex RPLND (41.7 versus 7.2%, P = 0.02) with the majority representing grade I-IIa. After a median follow-up of 28.5 months, four patients developed recurrent disease and one patient died of the disease. Conclusions: Few patients with advanced GCT need complex vascular, skeletal or intestinal surgery in an interdisciplinary setting with good functional and oncological outcome. Due to the complexity, treatment should be performed at specialized centres.

[Second neoplasms after percutaneous radiotherapy]. / Sekundärmalignome nach perkutaner Radiotherapie.

Radiation therapy represents an alternative treatment to radical prostatectomy in the management of clinically localized prostate cancer. Radiation-induced second neoplasms are defined by a latency period of at least 5 years, location within the field of radiation therapy, and a histology which differs from the primary tumor. Based on the data in the literature, there is a consistently increased risk of bladder cancer (HR: 1.67, 95% CI 1.55-1.80), rectal cancer (HR: 1.79, 95% CI 1.34-2.38), and colorectal cancer (HR: 1.79, 95% CI 1.34-23.8) following percutaneous radiation therapy. Following brachytherapy only an increased for the development of bladder cancer (HR: 2.14, 95% CI 1.03-3.94) has been observed. The incidence of second neoplasms increases significantly and continuously with the posttreatment time interval. Although bladder cancers following RT of the prostate are usually more locally advanced and of high grade, no negative impact in terms of overall survival and cancer-specific survival has been observed. Symptoms or findings of microhematuria need to be examined thoroughly after radiation therapy to identify bladder cancer quite early.

Seminal parameters of chronic male genital inflammation are associated with disturbed sperm DNA integrity.

Definition of chronic male genital tract inflammation and its impact on male infertility is still a matter of debate. In particular, DNA integrity has been reported to be disturbed in subfertile men. Thus, the aim of this study was to investigate an association of DNA integrity to altered standard semen parameters as well as inflammatory parameters such as peroxidase-positive cells, macrophages and seminal interleukin-6 concentration. Macrophages were detected by CD18/HLA-Dr staining, and DNA integrity was analysed by acridine orange staining using flow cytometry. Interleukin-6 was detected by ELISA. Normal DNA integrity showed a significant correlation to sperm number and progressive motility. Moreover, a significant inverse correlation of DNA integrity to Interleukin-6 and macrophages could be demonstrated. Further on, seminal interleukin-6 also significantly correlated to macrophages. No association has been observed between the number of peroxidase-positive cells and normal DNA integrity. As disturbed DNA integrity has been reported to negatively influence spermatozoon-egg interaction and even fertilisation rates following ICSI, and as early miscarriages have been associated with sperm DNA damage, it should be screened very carefully for male genital tract inflammations in couples undergoing infertility treatment. Measuring Interleukin-6 seems superior to assessment of the number of leucocytes alone and additional assessment of DNA integrity into the diagnostic work-up should be considered.