EnGraft: a multicentre, open-label, randomised, two-arm, superiority study protocol to assess bioavailability and practicability of Envarsus® versus Advagraf™ in liver transplant recipients.

BACKGROUND: Graft rejection and chronic CNI toxicity remain obstacles to organ transplant success. Current formulations of tacrolimus, such as Prograf® and Advagraf™, exhibit limitations in terms of pharmacokinetics and tolerability, related in part to suboptimal bioavailability. As dosing non-compliance can result in graft rejection, the once daily formulation of tacrolimus, Advagraf™, was developed (vs 2x/day Prograf®). Benefits of Advagraf™ are counterbalanced by delayed achievement of therapeutic trough levels and need for up to 50% higher doses to maintain Prograf®-equivalent troughs. Envarsus® is also a prolonged-release once-daily tacrolimus formulation, developed using MeltDose™ drug-delivery technology to increase drug bioavailability; improved bioavailability results in low patient drug absorption variability and less pronounced peak-to-trough fluctuations. In phase III de novo kidney transplant studies, Envarsus® proved non-inferior to twice-daily tacrolimus; however, no phase IV studies show superiority of Envarsus® vs Advagraf™ in de novo liver transplant (LTx) recipients. METHODS: The EnGraft compares bioavailability and tests superiority of Envarsus® (test arm) versus Advagraf™ (comparator arm) in de novo LTx recipients. A total of 268 patients from 15 German transplant centres will be randomised 1:1 within 14 days post-LTx. The primary endpoint is dose-normalised trough level (C/D ratio) measured 12 weeks after randomisation. Secondary endpoints include the number of dose adjustments, time to reach first defined trough level and incidence of graft rejections. Additionally, clinical and laboratory parameters will be assessed over a 3-year period. DISCUSSION: C/D ratio is an estimate for tacrolimus bioavailability. Improving bioavailability and increasing C/D ratio using Envarsus could reduce renal dysfunction and other tacrolimus-related toxicities; previous trials have shown that a higher C/D ratio (i.e. slower tacrolimus metabolism) is not only associated with improved renal function but also linked to reduced neurotoxic side effects. A higher C/D ratio could improve clinical outcomes for LTx recipients; EnGraft has begun, with one third of patients recruited by January 2022. TRIAL REGISTRATION: This trial has been registered (4 May 2020) in the EU Clinical Trials Register, EudraCT-Nummer: 2020-000796-20. Additionally, this trial has been registered (22 January 2021) at ClinicalTrials.gov: NCT04720326. The trial received a favourable opinion from the concerned lead ethics committee at the University of Regensburg, under the reference 20-1842-112.

Endoscopic vacuum therapy significantly improves clinical outcomes of anastomotic leakages after 2-stage, 3-stage, and transhiatal esophagectomies.

BACKGROUND: Anastomotic leakages after esophagectomies continue to constitute significant morbidity and mortality. Intrathoracic anastomoses pose a high risk for mediastinitis, sepsis, and death, if a leak is not addressed timely and appropriately. However, there are no standardized treatment recommendations or algorithms as for how to treat these leakages. METHODS: The study included all patients at the University Hospital Regensburg, who developed an anastomotic leakage after esophagectomy with gastric pull-up reconstruction from 2007 to 2022. Patients receiving conventional treatment options for an anastomotic leakage (stents, drainage tubes, clips, etc.) were compared to patients receiving endoscopic vacuum-assisted closure (eVAC) therapy as their mainstay of treatment. Treatment failure was defined as cervical esophagostomy formation or death. RESULTS: In total, 37 patients developed an anastomotic leakage after esophagectomy with a gastric pull-up reconstruction. Twenty patients were included into the non-eVAC cohort, whereas 17 patients were treated with eVAC. Treatment failure was observed in 50% of patients (n = 10) in the non-eVAC cohort and in 6% of patients (n = 1) in the eVAC cohort (p < 0.05). The 90-day mortality in the non-eVAC cohort was 15% (n = 3) compared to 6% (n = 1) in the eVAC cohort. Cervical esophagostomy formation was required in 40% of cases (n = 8) in the non-eVAC cohort, whereas no patient in the eVAC cohort underwent cervical esophagostomy formation. CONCLUSION: eVAC therapy for leaking esophagogastric anastomoses appears to be superior to other treatment strategies as it significantly reduces morbidity and mortality. Therefore, we suggest eVAC as an essential component in the treatment algorithm for anastomotic leakages following esophagectomies, especially in patients with intrathoracic anastomoses.

Predictive preoperative clinical score for patients with liver-only oligometastatic colorectal cancer.

BACKGROUND: Resection of liver metastases from colorectal cancer (CRC) in the oligometastatic stage improves survival and is a potentially curative treatment. Thus, predictive scores that reliably identify those patients who especially benefit from surgery are essential. PATIENTS AND METHODS: In this multicenter analysis, 512 patients had undergone surgery for liver metastases from CRC. We investigated distinct cancer-specific risk factors that are routinely available in clinical practice and developed a predictive preoperative score using a training cohort (TC), which was thereafter tested in a validation cohort (VC). RESULTS: Inflammatory response to the tumor, a right-sided primary tumor, multiple liver metastases, and node-positive primary tumor were significant adverse variables for overall survival (OS). Patients were stratified in five groups according to the cumulative score given by the presence of these risk factors. Median OS for patients without risk factors was 133.8 months [95% confidence interval (CI) 81.2-not reached (nr)] in the TC and was not reached in the VC. OS decreased significantly for each subsequent group with increasing number of risk factors. Median OS was significantly shorter (P < 0.0001) for patients presenting all four risk factors: 14.3 months (95% CI 10.5 months-nr) in the TC and 16.6 months (95% CI 14.6 months-nr) in the VC. CONCLUSIONS: Including easily obtainable variables, this preoperative score identifies oligometastatic CRC patients with prolonged survival rates that may be cured, and harbors potential to be implemented in daily clinical practice.

Stereotactic Percutaneous Electrochemotherapy as Primary Approach for Unresectable Large HCC at the Hepatic Hilum.

Electrochemotherapy (ECT) is a novel non-thermal ablative technique that combines chemotherapy and the application of electric pulses for reversible cell membrane electroporation. This method was recently performed in the treatment of deep-seated liver tumors during open surgery but experience about percutaneous ECT is rare and further developments like combination of percutaneous ECT with stereotactic navigated devices may be very promising. We report on a case of a 4.7 × 4.5 × 3.5 cm unresectable HCC at the hepatic hilum adjacent to the major vessels and the bile duct that was successfully treated using percutaneous ECT in combination with stereotactic navigation. Follow-up imaging 6 weeks and 6 months after ECT showed complete response.

Hepatocellular carcinoma progression during bridging before liver transplantation.

BACKGROUND: Recipient selection for liver transplantation in hepatocellular carcinoma (HCC) is based primarily on criteria affecting the chance of long-term success. Here, the relationship between pretransplant bridging therapy and long-term survival was investigated in a subgroup analysis of the SiLVER Study. METHODS: Response to bridging, as defined by comparison of imaging at the time of listing and post-transplant pathology report, was categorized into controlled versus progressive disease (more than 20 per cent tumour growth or development of new lesions). RESULTS: Of 525 patients with HCC who had liver transplantation, 350 recipients underwent pretransplant bridging therapy. Tumour progression despite bridging was an independent risk factor affecting overall survival (hazard ratio 1.80; P = 0.005). For patients within the Milan criteria (MC) at listing, mean overall survival was longer for those with controlled versus progressive disease (6.8 versus 5.8 years; P < 0.001). Importantly, patients with HCCs outside the MC that were downsized to within the MC before liver transplantation had poor outcomes compared with patients who never exceeded the MC (mean overall survival 6.2 versus 6.6 years respectively; P = 0.030). CONCLUSION: Patients with HCCs within the MC that did not show tumour progression under locoregional therapy had the best outcomes after liver transplantation. Downstaging into the limits of the MC did not improve the probability of survival.Prognostic factors determining the long-term success of liver transplantation in patients with hepatocellular carcinoma are still under discussion. A subgroup analysis of the SiLVER trial showed that disease control under bridging therapy is strongly associated with improved prognosis in terms of overall survival. However, in tumours exceeding the limits of the Milan criteria, downstaging did not restore the probability of survival compared with that of patients within the Milan criteria.

Reversal of end-ileostomy in patients with Crohn's disease.

PURPOSE: End-ileostomy after two-staged ileocolic resection is frequently performed in Crohn's disease patients at high risk for postoperative complications. However, there is paucity on data regarding the morbidity after the stoma reversal. METHODS: One hundred thirty patients undergoing closure of end-ileostomy between 1994 and 2016 were included. Data collection was retrospective in 11 first, and it was prospective in 119 last patients. Anastomotic complications were defined as anastomotic leak, perianastomotic abscess, and perianastomotic peritonitis. RESULTS: The median interval between ileostomy construction and reversal was 4.0 months. Ninety-seven of 121 patients with available data (80%) gained weight between both surgeries. Hemoglobin level increased between surgeries in 107 patients (85%). Fifteen patients (11.5%) received parenteral fluid substitution or parenteral nutrition between both surgeries. There were 37 hospital readmissions during the time between stoma construction and reversal (29%). After ileostomy reversal, 14 patients developed anastomotic complications (11%). By multivariate regression analysis, preoperative steroid intake (hazard ratio 4.5, 95% CI: 1.11-18.0, p = 0.035) and hospital readmission for infectious complications (HR 4.5, 95% CI: 1.11-18.0, p = 0.035) were statistically significantly associated with an increased risk to develop postoperative anastomotic complications. There were no postoperative deaths. CONCLUSION: Closure of end-ileostomy could be complicated by some serious morbidity. These risks should be taken into consideration weighing carefully between the one- and two-stage ileocolic resection in Crohn's disease patients.

Super selective percutaneous transhepatic coil embolization of intrahepatic pseudoaneurysm after pediatric liver transplantation: a case report.

BACKGROUND: Intrahepatic arterial pseudoaneurysms are a rare, life-threatening complication after pediatric liver transplantation. Treatment of choice represents interventional radiological management with endovascular embolization of the segmental artery proximal and distal to the aneurysm. However, this technique results in loss of arterial perfusion distal to the aneurysm with subsegment arterial ischemia. CASE PRESENTATION: We report a case of a 1-year-old girl with a pseudoaneurysm in the split-liver graft. Direct percutaneous, transhepatic access to the pseudoaneurysm was performed followed by super selective coil application into the aneurysm. CONCLUSION: Super selective percutaneous, transhepatic coil application is feasible even in pediatric patients after liver transplantation and results in preservation of the entire course of the liver artery.

[Intraoperative ultrasound in visceral surgery]. / Intraoperativer Ultraschall in der Viszeralchirurgie.

BACKGROUND: Intraoperative ultrasound is a routine procedure in abdominal surgery. Not only detection of focal lesions but also perfusion and elasticity analyses using color-coded Doppler sonography, contrast-enhanced ultrasound and elastography enable highly sensitive and highly specific diagnostics, especially in oncological surgery. OBJECTIVE: This article provides an overview on current techniques of intraoperative ultrasound and gives an outlook on future possibilities and applications. MATERIAL AND METHODS: Literature-based presentation of evidence-based intraoperative ultrasound, discussion of current basic research and expert recommendations. RESULTS: Modern intraoperative ultrasound is a highly efficient technique for detection and characterization of focal space-occupying lesions in surgery of benign and malignant diseases. CONCLUSION: Intraoperative ultrasound is a highly sensitive and specific diagnostic tool, providing real-time diagnostics with a manageable amount of technical equipment. Thus, preoperative diagnostics can be refined, partly resulting in a modification of intraoperative treatment management. Future developments in the fields of digital image fusion with preoperative sectional imaging, optical guidance of surgical instruments and molecular targeted tumor therapy will increase the importance of intraoperative sonography even more.

Mortality after liver surgery in Germany.

BACKGROUND: Mortality rates after liver surgery are not well documented in Germany. More than 1000 hospitals offer liver resection, but there is no central regulation of infrastructure requirements or outcome quality. METHODS: Hospital mortality rates after liver resection were analysed using the standardized hospital discharge data (Diagnosis-Related Groups, ICD-10 and German operations and procedure key codes) provided by the Research Data Centre of the Federal Statistical Office and Statistical Offices of the Länder in Wiesbaden, Germany. RESULTS: A total of 110 332 liver procedures carried out between 2010 and 2015 were identified. The overall hospital mortality rate for all resections was 5·8 per cent. The mortality rate among 17 574 major hepatic procedures was 10·4 per cent. Patients who had surgery for colorectal liver metastases (CRLMs) had the lowest mortality rate among those with malignancy (5·5 per cent), followed by patients with gallbladder cancer (7·1 per cent), hepatocellular carcinoma (9·3 per cent) and intrahepatic cholangiocarcinoma (11·0 per cent). Patients with extrahepatic cholangiocarcinoma had the highest mortality rate (14·6 per cent). The mortality rate for extended hepatectomy was 16·2 per cent and the need for a biliodigestive anastomosis increased this to 25·5 per cent. Failure to rescue after complications led to mortality rates of more than 30 per cent in some subgroups. There was a significant volume-outcome relationship for CRLM surgery in very high-volume centres (mean 26-60 major resections for CRLMs per year). The mortality rate was 4·6 per cent in very high-volume centres compared with 7·5 per cent in very low-volume hospitals (odds ratio 0·60, 95 per cent c.i. 0·42 to 0·77; P < 0·001). CONCLUSION: This analysis of outcome data after liver resection in Germany suggests that hospital mortality remains high. There should be more focused research to understand, improve or justify factors leading to this result, and consideration of centralization of liver surgery.

ANTECEDENTES: En Alemania, los datos de mortalidad después de la cirugía no están bien documentados. En más de 1.000 hospitales se realizan resecciones hepáticas, pero no existe una regulación central de los prerrequisitos estructurales necesarios y de la calidad de los resultados. MÉTODOS: Las tasas de mortalidad hospitalaria relacionadas con las resecciones hepáticas se analizaron utilizando los datos estandarizados del alta hospitalaria (Diagnóstico de grupos relacionados, DRG), la clasificación internacional de enfermedades 10 (ICD10) y la clave de procedimientos y operaciones (códigos OPS) proporcionados por el RDC de la Oficina Federal de Estadística y Oficinas de Estadística de Länder en Wiesbaden, Alemania. RESULTADOS: Se identificaron un total de 110.332 procedimientos hepáticos (de 2010 a 2015). La tasa global de mortalidad hospitalaria para todas las resecciones fue del 5,8%. Las resecciones hepáticas mayores (n = 15.333) presentaron una mortalidad del 10,4%. Los pacientes con metástasis hepáticas colorrectales (colorectal liver metastases, CRLM) tuvieron la mortalidad más baja de entre los pacientes con neoplasias malignas (5,5%), seguidos de los pacientes con cáncer de vesícula biliar (7,1%), colangiocarcinoma intrahepático (intrahepatic colangiocarcinoma, iCC) (11,0%) y carcinoma hepatocelular (hepatocellular carcinoma, HCC) (9,3%). Los pacientes con colangiocarcinoma extrahepático (extrahepatic cholangiocarcinoma, eCC) presentaron la mortalidad más alta (14,6%). Las hepatectomías extendidas (16,2%) y la necesidad de una anastomosis biliodigestiva (biliodigestive anastomosis, BDA) aumentaron la mortalidad a un 25,5%. La falta de solución de algunas complicaciones llevó a tasas de mortalidad de más del 30% en algunos subgrupos. Hubo una relación significativa volumen-resultado para las CRLM en centros de alto volumen (25,3 a 59,7 resecciones mayores/año; razón de oportunidades, odds ratio, OR 0,60, i.c. del 95%: 0,42-0,77; P < 0,001), lo que resultó en una disminución en las tasas de mortalidad de 7,5/6,4/7,5/6,5% a 4,6%. CONCLUSIÓN: El análisis de los resultados después de la resección hepática en Alemania muestra una alta mortalidad hospitalaria inesperada. Este análisis indica la necesidad de efectuar una investigación más específica para comprender, mejorar o justificar los factores que determinan estos hallazgos.

Risk of postoperative morbidity in patients having bowel resection for colonic Crohn's disease.

BACKGROUND: The aim of the present multicenter study was to analyze the incidence and risk factors associated with postoperative morbidity in patients who had colorectal resection for colonic Crohn's disease. METHODS: Consecutive patients undergoing colorectal resection for colonic Crohn's disease at seven surgical units in 1992-2017 were included. Exclusion criteria were: proctectomy for perianal disease, surgery for cancer, previous colectomies, surgery before 1998. Abdominal colectomy and proctocolectomy were defined as extended resections; all other operations were classified as segmental resections. Postoperative intraabdominal septic complications (IASC) were: anastomotic leaks, peritonitis and abscess. RESULTS: One hundred ninety-nine patients met the inclusion criteria: 116 patients had segmental resections and extended resections were performed in 83 patients. An anastomosis was constructed in 122 patients and an additional stoma was formed in 15 of those cases. Segmental resections were performed significantly more frequently in stricturing or penetrating disease (93% vs. 61%, p < 0.001) and were completed by an anastomosis more often than extended resections (78% vs. 37%, p < 0.001). The overall IASC rate was 17%. On multivariate analysis, formation of an anastomosis (Hazard ratio 2.9; 95% CI 1.1-7.7; p = 0.036) and preoperative hemoglobin level of < 10 g/dl (Hazard ratio 3.1; 95% CI 1.1-9.1; p = 0.034) were associated with an increase of postoperative IASC rate. Preoperative medication did not influence postoperative outcome. CONCLUSIONS: Severe preoperative anemia is associated with an increased postoperative morbidity. Resections completed by an anastomosis pose an increased postoperative complication risk in patients with colonic Crohn's disease as compared to resections without an anastomosis.

[Influence of social characteristics on the duration of treatment, severity of the disease and social support of patients in a surgical intensive care unit]. / Einfluss sozialer Charakteristika auf die Behandlungsdauer, Erkrankungsschwere und soziale Unterstützung von Patienten einer operativen Intensivstation.

BACKGROUND: In critical illnesses low socioeconomic status (SES) is associated with higher morbidity and mortality. In addition to the SES, further factors at an individual level (e.g., sex, health insurance status and place of residence) may influence the severity of illness and medical treatment. We investigated these additional parameters in a secondary analysis of the ECSSTASI data. METHODS: Within the framework of the ECSSTASI study, 996 patients were recruited from a surgical intensive care unit. We examined the influence of sex, insurance status and place of residence on health-related behavior, disease severity, duration of intensive care and ventilation (28 ventilator-free days score, 28-VFDS) and social support by the next of kin. Multivariate-adjusted logistic regression analyses were carried out and odds ratios (OR) are presented with corresponding 95% confidence intervals. RESULTS: Among patients admitted to the intensive care unit, the disease severity (SOFA score >5) was significantly lower in women than in men (OR 0.62 [0.45-0.87]). Increasing size of the patient's town of residence was associated with a significantly shorter duration of treatment on the intensive care unit (OR 0.54 [0.32-0.91]). An increasing number of persons in the household was associated with a significantly increased risk of being ventilated longer compared to 1­person households (p = 0.028). Patients with private insurance (OR 1.87 [1.28-2.70]), patients from households with ≥4 persons (OR 1.92 [1.1-3.33]) and patients without German citizenship (OR 2.56 [1.39-4.55]) were visited significantly more often by next of kin. CONCLUSION: In addition to the SES, sociodemographic characteristics of the individual patient are associated with the course of treatment in intensive care medicine. The extent of social support by the next of kin depends on intercultural and individual patient characteristics. An increasing size of the town of residence and private health insurance status positively influence intensive care outcomes. In order to evaluate these data, further epidemiological studies in intensive care medicine are necessary.

[Surgical innovations in treatment of metastatic colorectal cancer : Complexity of metastatic surgery as example for personalized medicine]. / Chirurgische Innovationen in der Therapie des metastasierten kolorektalen Karzinoms : Die Komplexität der Metastasenchirurgie als Beispiel für personalisierte Medizin.

BACKGROUND: Extensive, bilobular and multifocal colorectal liver metastases (CLM) or metastases that are critically situated require an experienced surgeon and advanced surgical techniques to enable curative resection. OBJECTIVE: This article describes the toolbox of hepato-oncologic surgery including functional augmentation of liver segments by portal vein embolization/ligation, combinations of ablation and resection, two-stage resections and in situ split liver resection, also known as associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). Furthermore, the curative resection of extrahepatic, oligometastatic disease are briefly discussed. MATERIAL AND METHODS: Review of current literature as well as discussion of the ALPPS procedure, which was developed at our institute. RESULTS: In recent years, oncologic resections for CLM have been significantly refined, leading to a constant increase of curative resection rates. CONCLUSION: In a multimodality treatment setting, surgical resection of CLM remains the gold standard curative approach and even in the event of presumed hopeless cases with extensive metastasis, experienced hepatobiliary surgeons must evaluate the resectability of colorectal metastases.

Efficiency of contrast enhanced ultrasound for immediate assessment of ablation status after intraoperative radiofrequency ablation of hepatic malignancies.

AIM: To evaluate the efficiency of intraoperative contrast enhanced ultrasound (Io-CEUS) for assessment of radiofrequency ablation (RFA) during liver tumor surgery. MATERIAL AND METHODS: Retrospective analysis was performed on a total number of 18 patients out of over 500 patients who underwent combined liver tumor surgery and RFA of 27 hepatic tumors between 02/2011 and 12/2016. Io-CEUS was performed by bolus injections of up to 10 ml sulphur hexaflourid microbubbles for diagnostic purposes. To guide the RFA up to 20 ml microbubbles were applied to monitor the procedure and assess the ablation status finally. A fully avascular area or absence of any residual vascularization intratumorally was considered technical success. These findings were correlated to findings of follow-up imaging results (CEUS, MRI, CT) at least 1 up to 40 months (mean 11 months) after surgery. RESULTS: 13 male and 5 female patients aged between 45-77 years (mean 59.2±17.1 years) with 26 malignant and one most probable benign hepatic lesion were treated with intraoperative RFA. Io-CEUS detected 23 preoperatively unknown liver lesions leading to a change in therapy in 13/18 cases (72,2%). All 27 treated lesions showed an avascular area immediately after RFA. According to follow-up imaging results (1 month - 3 years after surgery, mean follow-up time 11 months), 2/18 patients had local recurrences, 8 patients had distant intrahepatic recurrences or extrahepatic recurrence, 8 patients remained tumor-free. Thereby, a success rate of CEUS guided RFA of 89% could be obtained concerning the targeted liver lesions. CONCLUSION: Modern intraoperative ultrasound using B-mode and Io-CEUS is a valuable tool for optimization of diagnostic and therapeutic intraoperative liver procedures and ablative therapies.

Preservation of the superior rectal artery: influence of surgical technique on anastomotic healing and postoperative morbidity in laparoscopic sigmoidectomy for diverticular disease.

PURPOSE: To evaluate the impact of superior rectal artery (SRA) sparing technique on anastomotic leakage in laparoscopic sigmoidectomy for diverticular disease. MATERIAL AND METHODS: A retrospective multicenter analysis of all patients undergoing laparoscopic sigmoid resection for diverticular disease between 2002 and 2015 was conducted. Data were recorded in three hospitals: University Hospital Regensburg, Marienhospital Gelsenkirchen, and Städtisches Klinikum München Bogenhausen. The SRA was resected between 2002 and 2005. Since 2005, the artery was preserved in most cases. RESULTS: Two hundred sixty-seven patients were included. One hundred sixty patients presented with complicated diverticulitis (60%). The SRA was resected in 102 patients (group 1) and preserved in 157 patients (group 2, no data in eight cases). Anastomotic leakage occurred in 7% of patients in group 1 and 1.9% of patients in group 2 (p = 0.053). Duration of surgery was significantly shorter (157 vs. 183 min, p < 0.001) in group 2 patients. Length of hospital stay was without significant difference (group 1 8.2 days; group 2 8.3 days; p = 0.83). The conversion rate was higher in group 2 patients; however, the difference was not statistically significant (9 vs. 3%, p = 0.07). There was no significant difference between both groups regarding intraoperative complications and overall complication rate. The length of the resected specimen (19 vs. 21 cm, p = 0.001) was significantly shorter in group 2 patients. CONCLUSION: Preservation of the SRA seems to be associated with favorable outcome in patients undergoing laparoscopic sigmoid resection for diverticular disease.

Evaluation of a robotic system for irreversible electroporation (IRE) of malignant liver tumors: initial results.

OBJECTIVE: Comparison of conventional CT-guided manual irreversible electroporation (IRE) of malignant liver tumors and a robot-assisted approach regarding procedural accuracy, intervention time, dose, complications, and treatment success. METHODS: A retrospective single-center analysis of 40 cases of irreversible electroporation of malignant liver tumors in 35 patients (6 females, 29 males, average age 60.3 years). Nineteen of these ablation procedures were performed manually and 21 with robotic assistance. A follow-up (ultrasound, CT, and MRI) was performed after 6 weeks in all patients. RESULTS: The time from the planning CT scan to the start of the ablation as well as the dose-length product were significantly lower under robotic assistance (63.5 vs. 87.4 min, [Formula: see text]; 2132 vs. 4714 mGy cm, [Formula: see text]). The procedural accuracy, measured as the deviation of the IRE probes with respect to a defined reference probe, was significantly higher using robotic guidance (2.2 vs. 3.1 mm, [Formula: see text]). There were no complications. There was one incomplete ablation in the manual group. CONCLUSION: Robotic assistance for IRE of liver tumors allows for faster procedure times with higher accuracy while reducing radiation dose as compared to the manual placement of IRE probes.

[Extracorporeal CO2 removal as an alternative to tracheotomy in a patient with extubation failure]. / Extrakorporale CO2-Elimination als Alternative zur Tracheotomie bei Weaningversagen.

We report a patient with chest trauma who was admitted to the ICU after surgery. As he fulfilled protocol-based criteria, he was extubated 7 days after admission. However, despite intermittent non-invasive ventilation, the patient had to be re-intubated on day 10 owing to progressive hypercapnia. We decided to support the patient with a mid-flow veno-venous extracorporeal carbon dioxide removal (ECCO2­R) system instead of a tracheotomy. Sufficient CO2 removal was established with a blood flow of 1.5 l/min and the patient was successfully extubated within a few hours. After 5 days of ECCO2­R the patient could be weaned and transferred to a general ward in a stable condition.

CRS-HIPEC Prolongs Survival but is Not Curative for Patients with Peritoneal Carcinomatosis of Gastric Cancer.

PURPOSE: Peritoneal carcinomatosis (PC) is a dismal feature of gastric cancer that most often is treated by systemic palliative chemotherapy. In this retrospective matched pairs-analysis, we sought to establish whether specific patient subgroups alternatively should be offered a multimodal therapy concept, including cytoreductive surgery (CRS) and intraoperative hyperthermic chemotherapy (HIPEC). METHODS: Clinical outcomes of 38 consecutive patients treated with gastrectomy, CRS and HIPEC for advanced gastric cancer with PC were compared to patients treated by palliative management (with and without gastrectomy) and to patients with advanced gastric cancer with no evidence of PC. Kaplan-Meier survival curves and multivariate Cox regression models were applied. RESULTS: Median survival time after gastrectomy was similar between patients receiving CRS-HIPEC and matched control patients operated for advanced gastric cancer without PC [18.1 months, confidence interval (CI) 10.1-26.0 vs. 21.8 months, CI 8.0-35.5 months], resulting in comparable 5-year survival (11.9 vs. 12.1 %). The median survival time after first diagnosis of PC for gastric cancer was 17.2 months (CI 10.1-24.2 months) in the CRS-HIPEC group compared with 11.0 months (CI 7.4-14.6 months) for those treated by gastrectomy and chemotherapy alone, resulting in a twofold increase of 2-year survival (35.8 vs. 16.9 %). CONCLUSIONS: We provide retrospective evidence that multimodal treatment with gastrectomy, CRS, and HIPEC is associated with improved survival for patients with PC of advanced gastric cancer compared with gastrectomy and palliative chemotherapy alone. We also show that patients treated with CRS-HIPEC have comparable survival to matched control patients without PC. However, regardless of treatment scheme, all patients subsequently recur and die of disease.

Improved Detection of preclinical Colorectal Liver Metastases by High Resolution Ultrasound including Molecular Ultrasound Imaging using the targeted Contrast Agent BR55.

PURPOSE: Aim of the present study was to investigate the sensitivity of high resolution ultrasound (HRU), standard contrast-enhanced ultrasound (CEUS) and CEUS using a novel vascular endothelial growth factor receptor 2 (VEGFR2)-targeted contrast agent for the detection of hepatic metastases in a mouse model of colorectal cancer using clinical standard technology. MATERIALS AND METHODS: The human colon cancer cell line HT29, transfected with luciferase cDNA for in vivo bioluminescence monitoring, was injected intrasplenically into CB17.SCID mice. Mice were monitored weekly by bioluminescence and after 2 and 4.5 weeks by HRU and CEUS. Contrast media (untargeted BR1, targeted BR55) was applied and digital cine loops from the arterial phase (15 - 45 sec), portal venous phase (50 - 120 s) and late phases (3 - 5 min, 1hour) of the whole liver were analyzed. Data were correlated with postmortem histopathology. RESULTS: Without contrast enhancement, lesions > 4 mm were reliably detected. After use of untargeted CEUS, lesions > 2 mm were reliably detected and enhanced rim vascularization and late-phase wash-out was shown. With BR55, lesions > 0.8 mm were reliably detected with excellent documentation of vascularization. A persistent contrast enhancement was seen > 30 min after injection. Contrast-enhancement patterns with BR55 significantly correlated with CD31 (R2 = 0.74) and VEGFR2-immunohistochemistry (R2 = 0.66). CONCLUSION: Detection of metastases by HRU and CEUS was earlier and more accurate than monitoring via bioluminescence. In vivo monitoring of hepatic micrometastases can thus be performed without prior modification of cancer cells using standard technology.

Cyclosporine A Inhibits the T-bet-Dependent Antitumor Response of CD8(+) T Cells.

Transplant recipients face an increased risk of cancer compared with the healthy population. Although several studies have examined the direct effects of immunosuppressive drugs on cancer cells, little is known about the interactions between pharmacological immunosuppression and cancer immunosurveillance. We investigated the different effects of rapamycin (Rapa) versus cyclosporine A (CsA) on tumor-reactive CD8(+) T cells. After adoptive transfer of CD8(+) T cell receptor-transgenic OTI T cells, recipient mice received either skin grafts expressing ovalbumin (OVA) or OVA-expressing B16F10 melanoma cells. Animals were treated daily with Rapa or CsA. Skin graft rejection and tumor growth as well as molecular and cellular analyses of skin- and tumor-infiltrating lymphocytes were performed. Both Rapa and CsA were equally efficient in prolonging skin graft survival when applied at clinically relevant doses. In contrast to Rapa-treated animals, CsA led to accelerated tumor growth in the presence of adoptively transferred tumor-reactive CD8(+) OTI T cells. Further analyses showed that T-bet was downregulated by CsA (but not Rapa) in CD8(+) T cells and that cancer cytotoxicity was profoundly inhibited in the absence of T-bet. CsA reduces T-bet-dependent cancer immunosurveillance by CD8(+) T cells. This may contribute to the increased cancer risk in transplant recipients receiving calcineurin inhibitors.