Primary perioperative haemodynamic effects of ß-receptor blockade in patients with catecholamine-secreting tumours.

Introduction: Guidelines for the treatment of catecholamine-producing tumours strictly recommend starting ß-receptor blocking medication only after α-receptor blockade has been established. This recommendation is supported only by non-surgical case reports. However, in clinical practice ß-receptor blockade is often started before the diagnosis of a phaeochromocytoma is made. As we routinely treat patients with catecholamine-producing tumours without α-receptor blockade, our aim was to evaluate haemodynamic changes in such patients with and without ß-receptor blockade. Methods: Perioperative blood pressure was assessed prospectively for all patients. The primary outcome was the highest pre-, intra-, and postoperative systolic blood pressure in patients with or without a ß-receptor blockade. Secondary outcomes were the incidence of intraoperative systolic blood pressure peaks >250 mm Hg and hypotensive episodes. Subsequently, a propensity score matching (PSM) analysis was performed. Results: Out of 584 phaeochromocytoma and paraganglioma resections, 383 operations were performed without α-receptor blockade (including 84 with ß-receptor blockade). Before operation and intraoperatively, patients with ß-receptor blockade presented with higher systolic blood pressure (155 [25] and 207 [62] mm Hg) than patients without ß-receptor blockade (147 [24] and 183 [52] mm Hg; P=0.006 and P=0.001, respectively). Intraoperatively, patients with ß-receptor blockade demonstrated a higher incidence of hypotensive episodes (25% without vs 41% with ß-blockade; P<0.001). After propensity score matching no difference between the groups could be confirmed. Conclusion: Overall, patients with isolated ß-receptor blockade developed higher blood pressure before operation and intraoperatively. After propensity score matching a difference could no longer be detected. Overall, ß-receptor blockade seems to be more a sign for severe disease than a risk factor for haemodynamic instability.

Perioperative lung function following flow controlled ventilation for robot-assisted prostatectomies in steep trendelenburg position: an observational study.

BACKGROUND: Steep Trendelenburg position combined with capnoperitoneum can lead to pulmonary complications and prolonged affection of postoperative lung function. Changes in pulmonary function occur independent of different modes of ventilation and levels of positive end-expiratory pressure (PEEP). The effect of flow-controlled ventilation (FCV) has not been evaluated yet. We perioperatively measured spirometric lung function parameters in patients undergoing robot-assisted prostatectomy under FCV. Our primary hypothesis was that there is no significant difference in the ratio of the maximal mid expiratory and inspiratory flow (MEF50/MIF50) after surgery. METHODS: In 20 patients, spirometric measurements were obtained preoperatively, 40, 120, and 240 min and 1 and 5 days postoperatively. We measured MEF50/MIF50, vital capacity (VC), forced expiratory volume in 1 s (FEV1), and intraoperative ventilation parameters. RESULTS: MEF50/MIF50 ratio increased from 0.92 (CI 0.73-1.11) to 1.38 (CI 1.01-1.75, p < 0.0001) and returned to baseline within 24 h, while VC and FEV1 decreased postoperatively with a second nadir at 24 h and only normalized by the fifth day (p < 0.0001). Compared to patients with PCV, postoperative lung function changes similarly. CONCLUSION: Flow-controlled ventilation led to changes in lung function similar to those observed with pressure-controlled ventilation. While the ratio of MEF50/MIF50 normalized within 24 h, VC and FEV1 recovered within 5 days after surgery.

The KORE-INNOVATION trial, a prospective controlled multi-site clinical study to implement and assess the effects of an innovative peri-operative care pathway for patients with ovarian cancer: rationale, methods and trial design.

BACKGROUND: Advanced ovarian cancer is managed by extensive surgery, which could be associated with high morbidity. A personalized pre-habilitation strategy combined with an 'enhanced recovery after surgery' (ERAS) pathway may decrease post-operative morbidity. PRIMARY OBJECTIVE: To analyze the effects of a combined multi-modal pre-habilitation and ERAS strategy on severe post-operative morbidity for patients with ovarian cancer (primary diagnosis or first recurrence) undergoing cytoreductive surgery. STUDY HYPOTHESIS: A personalized multi-modal pre-habilitation algorithm entailing a physical fitness intervention, nutritional and psycho-oncological support, completed by an ERAS pathway, reduces post-operative morbidity. TRIAL DESIGN: This is a prospective, controlled, non-randomized, open, interventional two-center clinical study. Endpoints will be compared with a three-fold control: (a) historic control group (data from institutional ovarian cancer databases); (b) prospective control group (assessed before implementing the intervention); and (c) matched health insurance controls. INCLUSION CRITERIA: Patients with ovarian, fallopian, or primary peritoneal cancer undergoing primary surgical treatment (primary ovarian cancer or first recurrence) can be included. The intervention group receives an additional multi-level study treatment: (1) standardized frailty assessment followed by (2) a personalized tri-modal pre-habilitation program and (3) peri-operative care according to an ERAS pathway. EXCLUSION CRITERIA: Inoperable disease or neoadjuvant chemotherapy, simultaneous diagnosis of simultaneous primary tumors, in case of interference with the overall prognosis (except for breast cancer); dementia or other conditions that impair compliance or prognosis. PRIMARY ENDPOINT: Reduction of severe post-operative complications (according to Clavien- Dindo Classification (CDC) III-V) within 30 days after surgery. SAMPLE SIZE: Intervention group (n=414, of which approximately 20% insure with the participating health insurance); historic control group (n=198); prospective control group (n=50), health insurance controls (for those intervention patients who are members of the participating health insurance). ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The intervention phase started in December 2021 and will continue until June 2023. As of March 2023, 280 patients have been enrolled in the intervention group. The expected completion of the entire study is September 2024. TRIAL REGISTRATION: NCT05256576.

The role of factor XIII in surgery for advanced stage of epithelial ovarian cancer.

INTRODUCTION: Hereditary factor (F) XIII-deficiency is a known risk factor for postoperative complications, but data of acquired FXIII-deficiency in malignancies are limited. Therefore, we evaluated the role of acquired FXIII-deficiency in surgery for advanced epithelial ovarian cancer (EOC). MATERIALS AND METHODS: We performed a retrospective analysis of patients with known serum FXIII status and treatment between 2011 and 2018 at our center. We defined cohorts according to FXIII with values > 75% as normal (group A), 55-75% as reduced (group B) and < 55% as low (group C). Complications were classified according to the Clavien-Dindo Classification, class III-V complications were defined as severe. RESULTS: 347 patients with EOC were identified. 180 patients (51.2%) were in group A, 82 patients (23.6%) in group B, and 85 patients (24.4%) in group C. Lower levels of FXIII were associated with higher amount of ascites, FIGO IV, high grade serous histology, low albumin, and higher CA-125 levels. Regarding intraoperative variables, low FXIII was associated with longer duration of surgery, higher blood loss, higher surgical complexity score/number of bowel anastomosis and a higher probability for macroscopic residual disease. The risk of severe complications in group A was 12.2%, 24.4% in group B, and 31.8% in group C. In a multivariate model, low FXIII (OR 2.8), > 1 bowel anastomosis (OR 2.7), age-adjusted Charlson comorbidity index ≥ 4 (OR 3.6) and a longer duration of surgery (> 285 min.) were significant predictive factors for severe complications. CONCLUSION: FXIII is associated with tumor and treatment burden. A low level of FXIII is associated with postoperative complications. The knowledge about the presurgical serum FXIII-level might be helpful to plan the treatment strategy.

Clinical outcome in patients with primary epithelial ovarian cancer and germline BRCA1/2-mutation - real life data.

BACKGROUND: We evaluated the clinical impact of germline (g)BRCA1/2-mutation on initial disease presentation, surgical implications, surgical morbidity and survival in patients with advanced epithelial ovarian cancer (EOC) undergoing debulking surgery (DS). METHODS: Data of all consecutive EOC patients with stage III/IV, high-grade serous disease and known gBRCA1/2 status (gBRCA; non-gBRCA), who underwent DS at our department between 01/2011 and 06/2019 were analyzed. Associations between gBRCA-status and severe postoperative complications and survival were analyzed. RESULTS: gBRCA-status was determined in 50.1% (612/1221) of all patients. gBRCA was present in 21.9% (134/612). Significant differences were observed in terms of median age (p = 0.001) and histology (high-grade serous histology gBRCA: 98.5%, non-gBRCA 76.2%; p < 0.001). gBRCA-status had no impact on intraoperative disease presentation, surgical complexity or complete resection rate (gBRCA: 74.4%, non-gBRCA: 69.0%; p = 0.274). gBRCA-status was not predictive for severe postoperative complication (gBRCA: 12.0%, non-gBRCA: 19.1%; p = 0.082). Median PFS and OS was 31/22 and 71/53 months in patients with/without gBRCA-mutation, respectively. gBRCA was a significant prognostic factor for PFS (HR 0.57 p < 0.001) and for OS (HR 0.64, p = 0.048) after adjusting for established prognostic factors. CONCLUSIONS: gBRCA-status had no impact on initial disease presentation, surgical results or postoperative complications. gBRCA patients have a significantly longer PFS but the impact on the long term prognosis is unclear. Complete resection remains the most important prognostic factor in patients with EOC independent of gBRCA-status.

Anesthetic considerations for tracheobronchial surgery.

Tracheobronchial pathology can be related to trauma, infection, tumor, or a combination of these. Per definition, planning for tracheobronchial surgery can be complicated by the overlap of anesthesiological interests in airway management and the primary surgical field. Therefore, following a detailed description of the stenosis, management of tracheobronchial surgery requires an interdisciplinary discussion and individualized planning of the procedure. There are several options for intraoperative ventilation depending on the exact localization of the defect. Hence, different tubes and ventilation techniques from cross-field ventilation, to jet ventilation, or even spontaneous breathing under regional anesthesia, have to be discussed. Moreover, an innovative ventilation mode called flow-controlled ventilation (FVC) has been developed, which allows to apply standard tidal volumes through a narrow-bore endotracheal tube. In addition, the Ventrain has been developed as an emergency device following the same technique of an active expiration based on the Venturi principle and a controlled gas flow. In critical situations, it allows even ventilation through the working channel of a bronchoscope. Overall, tracheobronchial surgery is performed under total intravenous anesthesia and the aim of an early extubation at the end of surgery. Airway management has to be discussed and planned between surgeon and anesthesiologist. All of the steps of the procedure need constant and clear communication.

Skeletal Muscle Attenuation (Sarcopenia) Predicts Reduced Overall Survival in Patients with Advanced Epithelial Ovarian Cancer Undergoing Primary Debulking Surgery.

BACKGROUND: Sarcopenia was reported as a prognostic factor in cancer patients. Using computed tomography (CT), we analyzed the impact of sarcopenia on overall survival (OS) in patients with advanced epithelial ovarian cancer (EOC) after primary debulking surgery (PDS). METHODS: Preoperative CT scans of consecutive EOC patients (n = 323) were retrospectively assessed for skeletal muscle index (SMI) and muscle attenuation (MA; Hounsfield units [HU]). The optimal cut-off point for MA (32 HU) was calculated using the Martingale residuals method, and previously reported cut-offs for SMI were used. Logistic regression was used to determine univariate and multivariate factors associated with OS. RESULTS: Sarcopenia defined as SMI < 38.5, < 39, and 41 cm2/m2 was detected in 29.4, 33.7, and 47.1% of patients, respectively; however, none of these SMI cut-off levels were associated with OS. MA < 32 HU was present in 21.1% (68/323) of the total cohort. Significant differences between patients with MA < 32 and ≥ 32 HU were detected for median age (67 vs. 57 years), Eastern Cooperative Oncology Group (ECOG) > 0 (13.2 vs. 3.1%), comorbidity (age-adjusted Charlson Comorbidity Index [ACCI] ≥ 4; 36.8 vs. 13.3%), median body mass index (BMI; 27 vs. 24 kg/m2), International Federation of Gynecology and Obstetrics (FIGO) stage, histology (high-grade serous 95.6 vs. 84.7%), and complete resection (38.2 vs. 68.2%). MA < 32 HU remained a significant prognostic factor for OS in multivariate Cox regression analysis (hazard ratio 1.79, p = 0.003). Median OS in patients with MA < 32 HU versus MA ≥ 32 HU was 28 versus 56 months (p < 0.001). Furthermore, MA < 32 HU was significantly associated with OS in the prognostically poor population of patients with residual tumor (p = 0.015). CONCLUSIONS: Low MA was significantly associated with poor survival, especially in patients with residual tumor after PDS. MA assessment could be used for risk stratification after PDS.

International multicenter observational study on assessment of ventilatory management during general anaesthesia for robotic surgery and its effects on postoperative pulmonary complication (AVATaR): study protocol and statistical analysis plan.

INTRODUCTION: Robotic-assisted surgery (RAS) has emerged as an alternative minimally invasive surgical option. Despite its growing applicability, the frequent need for pneumoperitoneum and Trendelenburg position could significantly affect respiratory mechanics during RAS. AVATaR is an international multicenter observational study aiming to assess the incidence of postoperative pulmonary complications (PPC), to characterise current practices of mechanical ventilation (MV) and to evaluate a possible association between ventilatory parameters and PPC in patients undergoing RAS. METHODS AND ANALYSIS: AVATaR is an observational study of surgical patients undergoing MV for general anaesthesia for RAS. The primary outcome is the incidence of PPC during the first five postoperative days. Secondary outcomes include practice of MV, effect of surgical positioning on MV, effect of MV on clinical outcome and intraoperative complications. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board of the Hospital Israelita Albert Einstein. The study results will be published in peer-reviewed journals and disseminated at international conferences. TRIAL REGISTRATION NUMBER: NCT02989415; Pre-results.

65 YEARS OF THE DOUBLE HELIX: Genetics informs precision practice in the diagnosis and management of pheochromocytoma.

Although the authors of the present review have contributed to genetic discoveries in the field of pheochromocytoma research, we can legitimately ask whether these advances have led to improvements in the diagnosis and management of patients with pheochromocytoma. The answer to this question is an emphatic Yes! In the field of molecular genetics, the well-established axiom that familial (genetic) pheochromocytoma represents 10% of all cases has been overturned, with >35% of cases now attributable to germline disease-causing mutations. Furthermore, genetic pheochromocytoma can now be grouped into five different clinical presentation types in the context of the ten known susceptibility genes for pheochromocytoma-associated syndromes. We now have the tools to diagnose patients with genetic pheochromocytoma, identify germline mutation carriers and to offer gene-informed medical management including enhanced surveillance and prevention. Clinically, we now treat an entire family of tumors of the paraganglia, with the exact phenotype varying by specific gene. In terms of detection and classification, simultaneous advances in biochemical detection and imaging localization have taken place, and the histopathology of the paraganglioma tumor family has been revised by immunohistochemical-genetic classification by gene-specific antibody immunohistochemistry. Treatment options have also been substantially enriched by the application of minimally invasive and adrenal-sparing surgery. Finally and most importantly, it is now widely recognized that patients with genetic pheochromocytoma/paraganglioma syndromes should be treated in specialized centers dedicated to the diagnosis, treatment and surveillance of this rare neoplasm.

Minimally Invasive Surgery (MIS) in Children and Adolescents with Pheochromocytomas and Retroperitoneal Paragangliomas: Experiences in 42 Patients.

BACKGROUND: Pheochromocytomas (PH) and paragangliomas (PGL) are rare tumours in children accounting for about 1% of the paediatric hypertension. While minimally invasive surgical techniques are well established in adult patients with PH, the experience in children is extremely limited. To the best of our knowledge, we herewith present the largest series of young patients operated on chromaffin tumours by minimally invasive access. MATERIALS: In the setting of a prospective study (1/2001-12/2016), 42 consecutive children and adolescents (33 m, 9 f) were operated on. Thirty-seven patients (88%) suffered from inherited diseases. Twenty-six patients had PH, 11 presented retroperitoneal PGL, and five patients suffered from both. Altogether, 70 tumours (mean size 2.7 cm) were removed (45 PH, 25 PGL). All operations were performed by a minimally invasive access (retroperitoneoscopic, laparoscopic, extraperitoneal). Partial adrenalectomy was the preferred procedure for PH (31 out of 39 patients). Twenty patients received α-receptor blockade preoperatively. RESULTS: One patient died after induction of anaesthesia due to cardiac arrest. All other complications were minor. Conversion to open surgery was necessary in two cases with PGL. Median operating time for unilateral PH was 55 min, in bilateral cases 125, 143 min in PGs, and 180 min in combined cases. Median blood loss was 20 ml (range 0-1000). Blood transfusion was necessary in two cases. Intraoperative, systolic peak pressure was 170 ± 39 mmHg with α-receptor blockade and 191 ± 33 mmHg without α-receptor blockade (p = 0.41). The median post-operative hospital stay was 3 days. After a mean follow-up of 8.5 years, two patients presented ipsilateral recurrence (after partial adrenalectomy). All patients with bilateral PH (n = 13) are steroid independent post-operatively. CONCLUSIONS: PH and PGL in children and adolescents should preferably be removed by minimally invasive surgery. Partial adrenalectomy provides long-term steroid independence in bilateral PH and a low rate of (ipsilateral) recurrence. α-Receptor blockade may not be necessary in these patients.

Prognostic Value of the Age-Adjusted Charlson Comorbidity Index (ACCI) on Short- and Long-Term Outcome in Patients with Advanced Primary Epithelial Ovarian Cancer.

BACKGROUND: We evaluated the prognostic impact of the age-adjusted Charlson Comorbidity Index (ACCI) on both postoperative morbidity and overall survival (OS) in patients with advanced epithelial ovarian cancer (EOC) treated at a tertiary gynecologic cancer center. PATIENTS AND METHODS: Exploratory analysis of our prospectively documented tumor registry was performed. Data of all consecutive patients with stage IIIB-IV ovarian cancer who underwent primary cytoreductive surgery (PDS) from January 2000 to June 2016 were analyzed. Patients were divided into three groups, based on their ACCI: low (0-1), intermediate (2-3), and high (≥4), and postoperative surgical complications were graded according to the Clavien-Dindo classification (CDC). The Fisher's exact test, log-rank test, and Cox regression models were used to investigate the predictive value of the ACCI on postoperative complications and OS. RESULTS: Overall, 793 consecutive patients were identified; 328 (41.4%) patients were categorized as low ACCI, 342 (43.1%) as intermediate ACCI, and 123 (15.5%) as high ACCI. A high ACCI was significantly associated with severe postoperative complications (CDC 3-5; odds ratio 3.27, 95% confidence interval 1.97-5.43, p < 0.001). Median OS for patients with a low, intermediate, or high ACCI was 50, 40, and 23 months, respectively (p < 0.001), and the ACCI remained a significant prognostic factor for OS in multivariate analysis (p = 0.001). The same impact was observed in a sensitivity analysis including only those patients with complete tumor resection. CONCLUSION: The ACCI is associated with perioperative morbidity in patients undergoing PDS for EOC, and also has a prognostic impact on OS. The potential role of the ACCI as a selection criteria for different therapy strategies is currently under investigation in the ongoing, prospective, multicenter AGO-OVAR 19 trial.

The impact of type and number of bowel resections on anastomotic leakage risk in advanced ovarian cancer surgery.

OBJECTIVE: To identify risk factors for anastomotic leakage (AL) in patients undergoing primary advanced ovarian cancer surgery and to evaluate the prognostic implication of AL on overall survival in these patients. METHODS: We analyzed our institutional database for primary EOC and included all consecutive patients treated by debulking surgery including any type of full circumferential bowel resection beyond appendectomy between 1999 and 2015. We performed logistic regression models to identify risk factors for AL and log-rank tests and Cox proportional hazards models to evaluate the association between AL and survival. RESULTS: AL occurred in 36/800 (4.5%; 95% confidence interval [3%-6%]) of all patients with advanced ovarian cancer and 36/518 (6.9% [5%-9%]) patients undergoing bowel resection during debulking surgery. One hundred fifty-six (30.1%) patients had multiple bowel resections. In these patients, AL rate per patient was only slightly higher (9.0% [5%-13%]) than in patients with rectosigmoid resection only (6.9% [4%-10%]), despite the higher number of anastomosis. No independent predictive factors for AL were identified. AL was independently associated with shortened overall survival (HR 1.9 [1.2-3.4], p=0.01). CONCLUSION: In the present study, no predictive pre- and/or intraoperative risk factors for AL were identified. AL rate was mainly influenced by rectosigmoid resection and only marginally increased by additional bowel resections.

Dexmedetomidine's inhibitory effects on acetylcholine release from cholinergic nerves in guinea pig trachea: a mechanism that accounts for its clinical benefit during airway irritation.

BACKGROUND: Airway instrumentation can evoke upper airway reflexes including bronchoconstriction and cough which can cause serious complications including airway trauma, laryngospasm or bronchospasm which may in turn lead to difficulty with ventilation and hypoxemia. These airway events are mediated in part by irritant-induced neuronal modulation of airway tone and cough responses. We investigated whether the commonly used anesthetic agents dexmedetomidine, lidocaine or remifentanil attenuated neuronal and airway smooth muscle responses in the upper airways of guinea pigs. METHODS: The ability of dexmedetomidine, lidocaine or remifentanil to attenuate direct cholinergic nerve stimulation, C-fiber stimulation or direct smooth muscle contraction were studied using isolated tracheal rings from male guinea pigs under four paradigms; (1) the magnitude of contractile force elicited by cholinergic electrical field stimulation (EFS); (2) the amount of acetylcholine released during cholinergic EFS; (3) the direct airway smooth muscle relaxation of a sustained acetylcholine-induced contraction and (4) the magnitude of C-fiber mediated contraction. RESULTS: Dexmedetomidine (1-100 µM) and lidocaine (1 mM) attenuated cholinergic 30Hz EFS-induced tracheal ring contraction while remifentanil (10 µM) had no effect. Dexmedetomidine at 10 µM (p = 0.0047) and 100 µM (p = 0.01) reduced cholinergic EFS-induced acetylcholine release while lidocaine (10 µM-1 mM) and remifentanil (0.1-10 µM) did not. Tracheal ring muscle force induced by the exogenous addition of the contractile agonist acetylcholine or by a prototypical C-fiber analogue of capsaicin were also attenuated by 100 µM dexmedetomidine (p = 0.0061 and p = 0.01, respectively). The actual tracheal tissue concentrations of dexmedetomidine achieved (0.54-26 nM) following buffer application of 1-100 µM of dexmedetomidine were within the range of clinically achieved plasma concentrations (12 nM). CONCLUSIONS: The α2 adrenoceptor agonist dexmedetomidine reduced cholinergic EFS-induced contractions and acetylcholine release consistent with the presence of inhibitory α2 adrenoceptors on the prejunctional side of the postganglionic cholinergic nerve-smooth muscle junction. Dexmedetomidine also attenuated both exogenous acetylcholine-induced contraction and C-fiber mediated contraction, suggesting a direct airway smooth muscle effect and an underlying mechanism for cough suppression, respectively.

Airway Resistance in Patients with Obstructive Sleep Apnea Syndrome Following Robotic Prostatectomy.

BACKGROUND: Because minimally invasive surgery can improve postoperative recovery, it became the preferred technique for patients with significant comorbidities. However, steep Trendelenburg position and abdominal CO2-insufflation can lead to a significant increase in upper airway resistance and an alteration of overall lung function. In particular, patients who already suffer from an obstructive airway disease like obstructive sleep apnea syndrome (OSAS) might be at risk for postoperative airway complications. Therefore, we perioperatively performed spirometric tests in patients with OSAS undergoing robotic surgery in steep Trendelenburg position. METHODS: Twenty patients with OSAS were enrolled in the study. A day before surgery lung function measurements were performed and repeated preoperatively, 40, 120, and 240 minutes and 1 and 5 days postoperatively. We measured vital capacity (VC), forced expiratory volume in 1 second (FEV1), maximal mid expiratory and inspiratory flow (MEF50, MIF50), arterial oxygen saturation, and nasal flow. RESULTS: The ratio of MEF50 to MIF50, as an indicator of upper airway resistance, was increased significantly postoperatively and normalized within 24 hours (p < 0.0001), while FEV1 and VC were significantly reduced and recovered only partially as much as the fifth postoperative day (p < 0.0001). CONCLUSION: Airway resistance increased following robotic radical prostatectomy in Trendelenburg position in patients with OSAS. Two separate major effects can be observed. A significant increase of the upper airway resistance, which improved to preoperative conditions within 24 hours, and a reduction in FEV1 and VC, which recovered only partially as much as the fifth postoperative day.

Pattern of and reason for postoperative residual disease in patients with advanced ovarian cancer following upfront radical debulking surgery.

OBJECTIVE: Describing the pattern of and reasons for post-operative tumor residuals in patients with advanced epithelial ovarian cancer (AOC) operated in a specialized gynecologic cancer center following a strategy of maximum upfront debulking followed by systemic chemotherapy. METHODS: All consecutive AOC-patients treated between 2005 and 2015 due to stages FIGO IIIB/IV were included in this single-center analysis. RESULTS: 739 patients were included in this analysis. In 81 (11.0%) patients, chemotherapy had already started before referral. Of the remaining 658 patients, upfront debulking was indicated in 578 patients (87.8%), while 80 patients (12.8%) were classified ineligible for upfront debulking; mostly due to comorbidities. A complete tumor resection was achieved in 66.1% of the 578 patients with upfront surgery, 25.4% had residuals 1-10mm and 8.5% had residuals exceeding 10mm, and 12.5% of patients had multifocal residual disease. Most common localization was small bowel mesentery and serosa (79.8%), porta hepatis/hepatoduodenal ligament (10.1%), liver parenchyma (4.3%), pancreas (8.0%), gastric serosa (3.2%), and tumor surrounding/infiltrating the truncus coeliacus (2.7%); 14.9% of the patients had non-resectable supra diaphragmatic lesions. Size of residual tumor was significantly associated with progression-free and overall survival. CONCLUSIONS: Upfront debulking for AOC followed by systemic chemotherapy was our main treatment strategy in almost 90% of all patients. The majority experienced a benefit by this approach; while 11.7% of patients probably did not. Understanding sites and reason for residual disease may help to develop adequate surgical training programs but also to identify patients that would better benefit from alternative treatment strategies.

Effects of parecoxib on analgesia benefit and blood loss following open prostatectomy: a multicentre randomized trial.

BACKGROUND: This multi-centre, prospective, randomized, double-blind, placebo-controlled study was designed to test the hypotheses that parecoxib improves patients' postoperative analgesia without increasing surgical blood loss following radical open prostatectomy. METHODS: 105 patients (64 ± 7 years old) were randomized to receive either parecoxib or placebo with concurrent morphine patient controlled analgesia. Cumulative opioid consumption (primary objective) and the overall benefit of analgesia score (OBAS), the modified brief pain inventory short form (m-BPI-sf), the opioid-related symptom distress scale (OR-SDS), and perioperative blood loss (secondary objectives) were assessed. RESULTS: In each group 48 patients received the study medication for 48 hours postoperatively. Parecoxib significantly reduced cumulative opioid consumption by 24% (43 ± 24.1 mg versus 57 ± 28 mg, mean ± SD, p=0.02), translating into improved benefit of analgesia (OBAS: 2(0/4) versus 3(1/5.25), p=0.01), pain severity (m-BPI-sf: 1(1/2) versus 2(2/3), p < 0.01) and pain interference (m-BPI-sf: 1(0/1) versus 1(1/3), p=0.001), as well as reduced opioid-related side effects (OR-SDS score: 0.3(0.075/0.51) versus 0.4(0.2/0.83), p=0.03). Blood loss was significantly higher at 24 hours following surgery in the parecoxib group (4.3 g⋅dL(-1) (3.6/4.9) versus (3.2 g⋅dL(-1) (2.4/4.95), p=0.02). CONCLUSIONS: Following major abdominal surgery, parecoxib significantly improves patients' perceived analgesia. Parecoxib may however increase perioperative blood loss. Further trials are needed to evaluate the effects of selective cyclooxygenase-2 inhibitors on blood loss. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00346268.

Age and bupivacaine plasma concentrations following radical cystectomy.

PURPOSE: Continuous epidural analgesia with bupivacaine for postoperative analgesia can increase its plasma concentrations. Whether this effect can be aggravated with increasing age is unknown. Therefore, bupivacaine concentrations were prospectively monitored in patients undergoing radical cystectomies. METHODS: We analyzed plasma concentrations of bupivacaine in 38 consecutive patients scheduled for radical cystectomy. All patients received general and epidural anesthesia (10 ml bupivacaine 0.5% followed by bupivacaine 0.375% every 90 min) and postoperative continuous epidural analgesia (bupivacaine 0.25% with sufentanil 0.5 µg/ml). For 4 subsequent days, bupivacaine plasma concentrations were measured and the correlation of bupivacaine plasma concentrations with the patient's age were analyzed. Data (mean ± SD) were analyzed by 2-way ANOVA with post hoc analysis or regression analysis. RESULTS: The median age of the patients was 70 years (range 41-86). Postoperatively, bupivacaine plasma concentrations increased significantly. No correlation of plasma concentrations and age could be found. Maximal bupivacaine concentrations of the younger patients were not different from the older patients. No neurological or cardiovascular symptoms of bupivacaine intoxication were found. CONCLUSION: In conclusion, continuous epidural administration of bupivacaine leads to increasing plasma concentrations. No age dependent differences in bupivacaine plasma concentrations could be found. Therefore, in our patients with intact liver function, we did not find a reason for an age-related restriction in the use of continuous epidural analgesia.

Simulated life-threatening emergency during robot-assisted surgery.

BACKGROUND: With the increasing use of robot-assisted techniques for urologic and gynecologic surgery in patients with severe comorbidities, the risk of a critical incidence during surgery increases. Due to limited access to the patient the start of effective measures to treat a life-threatening emergency could be delayed. Therefore, we tested the management of an acute emergency in an operating room setting with a full-size simulator in six complete teams. METHODS: A full-size simulator (ISTAN, Meti, CA), modified to hold five trocars, was placed in a regular operating room and connected to a robotic system. Six teams (each with three nurses, one anesthesiologist, two urologists or gynecologists) were introduced to the scenario. Subsequently, myocardial fibrillation occurred. Time to first chest compression, removal of the robot, first defibrillation, and stabilization of circulation were obtained. After 7 weeks the simulation was repeated. RESULTS: The time to the start of chest compressions, removal of the robotic system, and first defibrillation were significantly improved at the second simulation. Time for restoration of stable circulation was improved from 417 ± 125 seconds to 224 ± 37 seconds (P=0.0054). Unexpected delays occurred during the first simulation because trocars had been removed from the patient but not from the robot, thus preventing the robot to be moved. CONCLUSION: Following proper training, resuscitation can be started within seconds. A repetition of the simulation significantly improved time for all steps of resuscitation. An emergency simulation of a multidisciplinary team in a real operating room setting can be strongly recommended.

[Anaesthesia for urological surgery - Anaesthesia for robotic assisted prostatectomies]. / Anästhesie in der Urologie - Anästhesie bei roboterassistierter Prostatektomie.

Because of excellent results, high patient satisfaction, and extraordinary surgical conditions robotic assisted prostatectomies have found a wide spread acceptance. Trendelenburg positioning, CO2-Insufflation, and installation of the robot system cause moderate hemodynamic and respiratory changes. Respiration can be compromised by significantly reduced pulmonary compliance during surgery and a marked CO2 load. Therefore, arterial blood gas controls during surgery can be recommended. Over hours edema of head and neck including the upper airways and an increase of the intraocular pressure can develop. There are no restrictions in the choice of the anesthetics. Careful positioning of the patient and critical intravenous fluid management are important determinants of a successful anesthetic management.