Robot-assisted laparoscopic radical cystectomy with intracorporeal ileal conduit diversion versus open radical cystectomy with ileal conduit for bladder cancer in an ERAS setup (BORARC): protocol for a single-centre, double-blinded, randomised feasibility study.

BACKGROUND: Radical cystectomy (RC) with urinary diversion is the recommended treatment for selected cases of non-metastatic high-risk non-muscle-invasive and muscle-invasive bladder cancer. It remains unknown whether robot-assisted laparoscopic cystectomy (RARC) offers any advantage in terms of safety compared to open cystectomy (ORC) in an Enhanced Recovery After Surgery (ERAS) setup. Blinded randomised controlled trials (RCTs) between RARC versus ORC have never been conducted in cystectomy patients. We will investigate the feasibility of conducting a double-blinded RCT comparing ORC with RARC with intra-corporal ileal conduit (iRARC) in an ERAS setup. METHODS: This is a single-centre, double-blinded, randomised (1:1) clinical feasibility study for patients with non-metastatic high-risk non-muscle-invasive or muscle-invasive bladder cancer scheduled for cystectomy. All participants are recruited from Rigshospitalet, Denmark. The planned sample size is 50 participants to investigate whether blinding of the surgical technique is feasible. Participants and postoperative caring physicians and nurses are blinded using a pre-study designed abdominal dressing and blinding of the patient's electronic health record. Study endpoints are assessed 90 days postoperatively. The primary aim is to study the frequency and pattern of unplanned unblinding after surgery and the number of participants who cannot guess the surgical technique at the day of discharge. Eleven secondary endpoints are assessed: length of stay, days alive and out of hospital, in-hospital complication rate, 30-day complication rate, 90-day complication rate, readmission rate, quality of life, blood loss, pain, rate of moderate/severe post-anaesthesia care unit (PACU) complications, and delirium. Participants are managed in an ERAS setup in both arms of the trial. DISCUSSION: We report on the design and objectives of a novel experimental feasibility study investigating whether blinding of the surgical technique in cystectomy patients is possible. This information is essential for the design of future blinded trials comparing ORC to RARC. There is a continued need to compare RARC and ORC in terms of both efficacy, safety, and oncological outcomes. Estimated end of study is March 2021. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03977831. Registered on the 6th of June 2019.

Case Report: Giant Paraganglioma of the Skull Base With Two Somatic Mutations in SDHB and PTEN Genes.

Head and neck paragangliomas (HNPGLs) are neuroendocrine tumors. They arise from the parasympathetic ganglia and can be either sporadic or due to hereditary syndromes (up to 40%). Most HNPGLs do not produce significant amounts of catecholamines. We report a case of a giant paraganglioma of the skull base with an unusually severe presentation secondary to excessive release of norepinephrine, with a good outcome considering the severity of disease. A 39-year-old Caucasian woman with no prior medical history was found unconscious and emaciated in her home. In the intensive care unit (ICU) the patient was treated for multi-organ failure with multiple complications and difficulties in stabilizing her blood pressure with values up to 246/146 mmHg. She was hospitalized in the ICU for 72 days and on the 31st day clinical assessment revealed jugular foramen syndrome and paralysis of the right n. facialis. A brain MRI confirmed a right-sided tumor of the skull base of 93.553 cm3. Blood tests showed high amounts of normetanephrine (35.1-45.4 nmol/L, ref <1.09 nmol/L) and a tumor biopsy confirmed the diagnosis of a paraganglioma. Phenoxybenzamine and Labetalol were used in high doses ((Dibenyline®, 90 mg x 3 daily) and labetalol (Trandate®, 200 + 300 + 300 mg daily) to stabilize blood pressure. The patient underwent two tumor embolization procedures before total tumor resection on day 243. Normetanephrine and blood pressure normalized after surgery (0.77 nmol/L, ref: < 1.09 nmol/L). The damage to the cranial nerve was permanent. Our patient was comprehensively examined for germline predisposition to PPGLs, however we did not identify any causal aberrations. A somatic deletion and loss of heterozygosity (LOH) of the short arm (p) of chromosome 1 (including SDHB) and p of chromosome 11 was found. Analysis showed an SDHB (c.565T>G, p.C189G) and PTEN (c.834C>G, p.F278L) missense mutation in tumor DNA. The patient made a remarkable recovery except for neurological deficits after intensive multidisciplinary treatment and rehabilitation. This case demonstrates the necessity for an early tertiary center approach with a multidisciplinary expert team and highlights the efficacy of the correct treatment with alpha-blockade.

Open vs robot-assisted radical cystectomy (BORARC): a double-blinded, randomised feasibility study.

OBJECTIVE: To examine surgical outcomes and feasibility of blinding patients and care providers to the surgical technique of radical cystectomy (RC). PATIENTS AND METHODS: Single-centre, parallel-group, double-blinded, randomised feasibility study of open RC (ORC) vs robot-assisted RC with intracorporeal urinary diversion (iRARC) in an 'Enhanced Recovery After Surgery' setup. A total of 50 patients aged ≥18 years with bladder cancer planned for RC with an ileal conduit were included. Patients with previous major abdominal/pelvic surgery, pelvic radiation or anaesthesiological contraindications were excluded. Primary outcomes were proportion of unblinded patients and success of blinding using Bang's Blinding Index. Secondary outcomes included length of stay (LOS), complication rates, blood loss, pain, and opioid consumption. RESULTS: A total of 26% of the patients were unblinded before discharge. We demonstrated that patients and doctors remained blinded for the allocated treatment, but nurses did not. Blood loss was greater in the ORC group as was operative time in the iRARC group. We found no difference in complication rate, LOS, or use of analgesics. CONCLUSIONS: The present study demonstrates that blinding of surgical technique in RC is possible. The results of secondary outcomes are consistent with the findings of previous unblinded randomised controlled trials. Our study highlights that it is possible to perform a blinded phase III study to explore the optimal surgical technique in RC.

Impact of Albumin on Coagulation Competence and Hemorrhage During Major Surgery: A Randomized Controlled Trial.

For patients exposed to a massive blood loss during surgery, maintained coagulation competence is important. It is less obvious whether coagulation competence influences bleeding during elective surgery where patients are exposed to infusion of a crystalloid or a colloid. This randomized controlled trial evaluates whether administration of 5% human albumin (HA) or lactated Ringer solution (LR) affects coagulation competence and in turn blood loss during cystectomy due to bladder cancer. Forty patients undergoing radical cystectomy were included to receive either 5% HA (n = 20) or LR (n = 20). Nineteen patients were analyzed in the HA group and 20 patients in the lactated Ringer group. Blinded determination of the blood loss was similar in the 2 groups of patients: 1658 (800-3300) mL with the use of HA and 1472 (700-4330) mL in the lactated Ringer group (P = 0.45). Yet, by thrombelastography (TEG) evaluated coagulation competence, albumin affected clot growth (TEG-angle 69 ±â€Š5 vs 74°â€Š±â€Š3°, P < 0.01) and strength (TEG-MA: 59 ±â€Š6 vs 67 ±â€Š6 mm, P < 0.001) more than LR. Furthermore, by multivariate linear regression analyses reduced TEG-MA was independently associated with the blood loss (P = 0.042) while administration of albumin was related to the changes in TEG-MA (P = 0.029), aPPT (P < 0.022), and INR (P < 0.033). This randomized controlled trial demonstrates that administration of HA does not affect the blood loss as compared to infusion of LR. Also the use of HA did not affect the need for blood transfusion, the incidence of postoperative complications, or the hospital in-stay. Yet, albumin decreases coagulation competence during major surgery and the blood loss is related to TEG-MA rather than to plasma coagulation variables.

Coagulation competence for predicting perioperative hemorrhage in patients treated with lactated Ringer's vs. Dextran--a randomized controlled trial.

BACKGROUND: Perioperative hemorrhage may depend on coagulation competence and this study evaluated the influence of coagulation competence on blood loss during cystectomy due to bladder cancer. METHODS: Forty patients undergoing radical cystectomy were included in a randomized controlled trial to receive either lactated Ringer's solution or Dextran 70 (Macrodex ®) that affects coagulation competence. RESULTS: By thrombelastography evaluated coagulation competence, Dextran 70 reduced "maximal amplitude" (MA) by 25 % versus a 1 % reduction with the administration of lactated Ringer's solution (P <0.001). Blinded evaluation of the blood loss was similar in the two groups of patients - 2339 ml with the use of Dextran 70 and 1822 ml in the lactated Ringer's group (P = 0.27). Yet, the blood loss was related to the reduction in MA (r = -0.427, P = 0.008) and by multiple regression analysis independently associated with MA (P = 0.01). Thus, 11 patients in the dextran group (58 %) developed a clinical significant blood loss (>1500 ml) compared to only four patients (22 %) in the lactated Ringer's group (P = 0.04). CONCLUSIONS: With the use of Dextran 70 vs. lactated Ringer's solution during cystectomy, a relation between hemorrhage and coagulation competence is demonstrated. Significant bleeding develops based on an about 25 % reduction in thrombelastography determined maximal amplitude. A multivariable model including maximal amplitude discriminates patients with severe perioperative bleeding during cystectomy. TRIAL REGISTRATION: The study was accepted on January 7(th), 2013 at www.clinicaltrialsregister.eu EudraCT 2012-005040-20.

Hydroxyethyl starch reduces coagulation competence and increases blood loss during major surgery: results from a randomized controlled trial.

OBJECTIVE: This study evaluated whether administration of hydroxyethyl starch (HES) 130/0.4 affects coagulation competence and influences the perioperative blood loss. BACKGROUND: Artificial colloids substitute blood volume during surgery; with the administration of HES 130/0.4 (Voluven, Fresenius Kabi, Uppsala, Sweden) only a minor effect on coagulation competence is expected. METHODS: Eighty patients were scanned for enrollment in the study, and 40 patients fulfilled the inclusion criteria. Two patients withdrew their consent to participate in the study, and 5 patients were excluded. Thus, 16 patients were randomized to receive lactated Ringer's solution and 17 to receive HES 130/0.4. RESULTS: Among the patients receiving HES 130/0.4, thrombelastography indicated reduced clot strength (P < 0.001) and blinded evaluation of the perioperative blood loss was 2.2 (range 0.5 to 5.0) versus 1.4 (range 0.5 to 2.4) L in the patients who received HES 130/0.4 or lactated Ringer, respectively (P < 0.038). The patients in the lactated Ringer's group, however, received more fluid (P < 0.0001) than those in the HES 130/0.4 group. There was no significant difference between the 2 groups with regard to frequency of reoperations or the length of hospital stay, but use of HES 130/0.4 was both more expensive and less efficacious than the use of lactated Ringer. CONCLUSIONS: Administration of HES 130/0.4 reduced clot strength and perioperative hemorrhage increased by more than 50%, while administration of lactated Ringer's solution provoked an approximately 2.5 times greater positive volume balance at the end of surgery.

[Herbal medicines--evidence and drug interactions in clinical practice]. / Naturlaegemidler--evidens og laegemiddelinteraktioner i klinisk praksis.

We present an evidence-based literature review of five commonly used herbs in Denmark: St John's wort, ginkgo biloba, valerian, garlic, and ginseng. Various drug interactions are associated with the intake of some herbal medicines, and may result in many clinical conditions. We bring this to the attention of clinical practitioners. Attention to clinical practice and recommendations for discontinuation of the five herbs are given before surgery. Physicians should be aware of and report potential drug interactions and adverse effects, so as to throw more light on this subject.