Effect of Hyperthermic Intraperitoneal Chemotherapy on Cytoreductive Surgery in Gastric Cancer With Synchronous Peritoneal Metastases: The Phase III GASTRIPEC-I Trial.

PURPOSE: In patients with peritoneal metastasis (PM) from gastric cancer (GC), chemotherapy is the treatment of choice. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are still being debated. This randomized, controlled, open-label, multicenter phase III trial (EudraCT 2006-006088-22; ClinicalTrials.gov identifier: NCT02158988) explored the impact on overall survival (OS) of HIPEC after CRS. PATIENTS AND METHODS: Adult patients with GC and histologically proven PM were randomly assigned (1:1) to perioperative chemotherapy and CRS alone (CRS-A) or CRS plus HIPEC (CRS + H). HIPEC comprised mitomycin C 15 mg/m2 and cisplatin 75 mg/m2 in 5 L of saline perfused for 60 minutes at 42°C. The primary end point was OS; secondary endpoints included progression-free survival (PFS), other distant metastasis-free survival (MFS), and safety. Analyses followed the intention-to-treat principle. RESULTS: Between March 2014 and June 2018, 105 patients were randomly assigned (53 patients to CRS-A and 52 patients to CRS + H). The trial stopped prematurely because of slow recruitment. In 55 patients, treatment stopped before CRS mainly due to disease progression/death. Median OS was the same for both groups (CRS + H, 14.9 [97.2% CI, 8.7 to 17.7] months v CRS-A, 14.9 [97.2% CI, 7.0 to 19.4] months; P = .1647). The PFS was 3.5 months (95% CI, 3.0 to 7.0) in the CRS-A group and 7.1 months (95% CI, 3.7 to 10.5; P = .047) in the CRS + H group. The CRS + H group showed better MFS (10.2 months [95% CI, 7.7 to 14.7] v CRS-A, 9.2 months [95% CI, 6.8 to 11.5]; P = .0286). The incidence of grade ≥3 adverse events (AEs) was similar between groups (CRS-A, 38.1% v CRS + H, 43.6%; P = .79). CONCLUSION: This study showed no OS difference between CRS + H and CRS-A. PFS and MFS were significantly better in the CRS + H group, which needs further exploration. HIPEC did not increase AEs.

[The Association of Surgical Oncology (ACO) curriculum "Surgical oncology"-Prerequisites for participation, registration and course]. / Das ACO-Kurrikulum "Chirurgische Onkologie" ­ Voraussetzungen zur Teilnahme, Anmeldung und Ablauf.

For solid malignancies of the gastrointestinal tract, surgical removal is a central pillar of treatment and often the only possibility to achieve a long-term cure. While there are additional qualifications for an oncological subspecialization in other surgical disciplines, such as gynecology or urology nothing comparable exists for visceral surgery in Germany, despite the fact that interdisciplinary cancer treatment strategies are becoming increasingly more complex. The Association of Surgical Oncology (ACO) in cooperation with the European Union of Medical Specialists (UEMS) has created the curriculum for surgical oncology, a structured further education concept, which concludes with the European Board of Surgical Qualification (EBSQ) examination. This results in a standardization and improvement in surgical and oncological treatment in Germany. Furthermore, successful graduates receive an ACO as well as a UEMS certificate and are Fellows of the European Board of Surgery (FEBS).

[Surgical treatment of pseudomyxoma peritonei-Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy]. / Chirurgische Therapie des Pseudomyxoma-peritonei-Syndroms ­ zytoreduktive Chirurgie und hypertherme intraperitoneale Chemotherapie.

BACKGROUND: Pseudomyxoma peritonei syndrome (PMP) is an orphan disease. Surgery is the fundament of treatment. METHOD: Short review summarizing the state of the art treatment. RESULTS: Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) form the foundations of treatment for PMP. The peritoneal cancer index should be preoperatively determined based on imaging and/or laparoscopy, intraoperatively validated and both should be documented. An extraperitoneal surgical preparation technique leads to effective en bloc resection of the peritoneum and the affected abdominal area. The HIPEC technique should be performed with mitomycin C for 60-90 min. Complete CRS (CC = 0, CC = 1) and the histological subtype are relevant for the prognosis. Structured educational programs and mentoring can optimize the learning curve. The aftercare should be performed at the surgical center. After follow-up imaging at 3 months after CRS, in the first 2 years a control should be carried out every 6 months. Thereafter, the intervals can be extended to 1 year. CONCLUSION: Standardized surgical treatment and HIPEC, optimized specific surgical training and structured follow-up at the center lead to an excellent long-term prognosis for patients with PMP.

Imaged guided surgery during arteriovenous malformation of gastrointestinal stromal tumor using hyperspectral and indocyanine green visualization techniques: A case report.

BACKGROUND: This case report demonstrates the simultaneous development of a gastrointestinal stromal tumour (GIST) with arteriovenous malformations (AVMs) within the jejunal mesentery. A 74-year-old male presented to the department of surgery at our institution with a one-month history of abdominal pain. Contrast-enhanced computed tomography revealed an AVM. During exploratory laparotomy, hyperspectral imaging (HSI) and indocyanine green (ICG) fluorescence were used to evaluate the extent of the tumour and determine the resection margins. Intraoperative imaging confirmed AVM, while histopathological evaluation showed an epithelioid, partially spindle cell GIST. CASE SUMMARY: This is the first case reporting the use of HSI and ICG to image GIST intermingled with an AVM. The resection margins were planned using intraoperative analysis of additional optical data. Image-guided surgery enhances the clinician's knowledge of tissue composition and facilitates tissue differentiation. CONCLUSION: Since image-guided surgery is safe, this procedure should increase in popularity among the next generation of surgeons as it is associated with better postoperative outcomes.

Oligometastatic disease and visceral resections in advanced malignant melanoma: a propensity-matched analysis.

PURPOSE: Malignant melanoma is among the tumours with the highest increase in incidence of solid tumours in Germany. While most patients are diagnosed at an early stage and show a good prognosis, advanced stages of malignant melanoma are accompanied with a poor prognosis and limited treatment options. Comparable to other tumour entities, the resection of visceral metastases could lead to a better prognosis. Supplementary, the subgroup of oligometastatic patients might benefit from surgical therapy to a greater extent. METHODS: This retrospective study analysed 351 patients treated between 2006 and 2017 at the University Hospital of Cologne. A total of 121 patients showed visceral metastases, with which we compared patients with a diffuse tumour spread to patients in an oligometastatic state. Furthermore, we evaluated the effect of visceral resection of oligometastatic, malignant melanoma. RESULTS: Our analysis showed that patients with an oligometastatic malignant melanoma had a significantly better prognosis than patients with a diffuse pattern of metastases, if they showed visceral metastases. Furthermore, the resection of visceral metastases leads to a significant gain in median overall survival time (13.6 vs. 34.2 months) and in progression-free survival (9.6 vs. 3.8 months). CONCLUSION: The resection of visceral metastases is a rational treatment option in advanced malignant melanoma. Although our study is limited by a small cohort of patients (n = 18), we believe that the resection of visceral metastases will be fundamental in the treatment of malignant melanoma. In particular, patients in an oligometastatic stage could be an eligible group for surgical treatment.

The influence of stereoscopic vision on surgical performance in minimal invasive surgery-a substudy of the IDOSP-Study (Influence of 3D- vs. 4 K-Display Systems on Surgical Performance in minimal invasive surgery).

PURPOSE: This study is a secondary analysis of the IDOSP trial published in the Annals of Surgery 2020. The aim of this study was to examine the influence of stereo acuity on surgical performance in a laparoscopic training parkour with 3D- versus 4 K-2D-display technique. METHODS: The surgical performance of medical students (MS), non-board-certified surgeons (NBC), and board-certified surgeons (BC) was compared using 3D- versus 4 K-2D-display technique at a training parkour in a randomized cross-over trial. Stereo acuity was tested by TNO and Titmus Stereo tests. RESULTS: Eighty-nine participants were included in this sub-trial. The median stereo acuity for all participants, measured with the Titmus test, was 25 s arc, with TNO test 30 s arc. Higher quality stereo vision, measured with the Titmus test, correlated significantly with a reduced parkour time (r = 0.26, p = 0.02) and error (r = 0.21, p = 0.048) with the 3D screen. The TNO test did not correlate significantly with parkour performance. There was no statistically significant correlation between parkour time nor error and stereo acuity using the 4 K system (p > 0.457 respectively). Higher age showed a significant correlation with lower stereo acuity measured with TNO (r = 0.21, p = 0.014), but not with the Titmus test (r = - 0.7, p = 0.39). Seven percent of the group "NBC and BC" showed reduced stereo acuity > 120 s arc with the Titmus test and 3% with the TNO test. CONCLUSION: High-quality stereo vision is of utmost importance for surgical skills using a 3D-display system. This was most obvious for MS and for tasks that place particularly high demands on hand-eye coordination. The Titmus test was more precise than the TNO test to predict the benefit of a 3D monitor system. Experience and fine motor skills could partly compensate for a poorer stereo acuity. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov (trial number: NCT03445429, registered February 26, 2018).

[Incidental Finding of Appendiceal Neuroendocrine Tumour]. / Zufallsbefund NEN Appendix.

With an incidence of 80%, neuroendocrine neoplasia (NEN) is the most common neoplasia of the appendix. In most cases, these tumours are diagnosed as an incidental finding after appendectomy with suspected appendicitis. They are usually highly differentiated neuroendocrine tumours. Due to their frequent location on the apex of the appendix, the NENs of the appendix are usually not the cause of the symptoms typical for appendicitis.Most patients (80-90%) receive adequate oncological treatment by laparoscopic or open appendectomy that has already been performed. However, if there are risk factors such as tumour size > 2 cm, location close to the base, angioinvasion, perforation or infiltration of neighbouring organs, proliferation index of > 2% or infiltration of the mesoappendix by more than 3 mm in the final histopathological finding, subsequent resection as an oncological right sided hemicolectomy is recommended .Due to their mostly early tumour stage at diagnosis without proven lymph node metastasis, patients with NEN of the appendix have an excellent 5-year survival rate of 70-85% across all tumour stages.

Adrenal Surgery in the Era of Multidisciplinary Endocrine Tumor Boards.

Work up of adrenal masses includes assessment of endocrine activity and malignancy risk. There is no indication for surgical removal of nonfunctional adrenal adenomas, according to the guidelines. In the present study, we aimed at evaluating the impact of a university endocrine tumor board on the quality of the indications for adrenal surgery at our institution. One hundred consecutive patients receiving primary adrenal surgery at the University Hospital of Cologne, Germany were included. Their demographics, clinic-pathologic characteristics, treatment and outcome were analyzed. In 55 (55%) cases, indication for surgery consisted in functional benign tumors, including Conn, Cushing adenomas and pheochromocytomas. Forty (40%) tumors were referred to surgery for malignancy suspicion and 5 (5%) myelolipomas were removed due to their size. Eighty-nine percent of surgeries were performed as minimally invasive procedures. Overall morbidity included two (2%) self-limiting pancreatic fistulas after left laparoscopic adrenalectomy for pheochromocytoma. All functional tumors were confirmed benign by final histology. Only 33 (82.5%) of 40 suspicious cases turned out to be malignant. Consequently, nonfunctional benign adenomas were "unnecessarily" removed in only 7 (7%) patients, with 6 (85.7%) of them having a history of extra-adrenal cancer and all of them fulfilling criteria for surgery, according to the international guidelines. In conclusion, the endocrine tumor board provided an excellent adherence to the guidelines with most surgeries being performed either for functional or malignant tumors. In nonfunctional tumors with history of extra adrenal cancer, CT guided biopsy might be considered for obviating surgery.

Effect of phone call distraction on the performance of medical students in an OSCE.

BACKGROUND: The usage of smartphones in the daily clinical routine is an essential aspect however it seems that they also present an important distractor that needs to be evaluated. The aim of this prospective study was the evaluation of the influence of phone calls as distractors on the performance levels of medical students during an objective structured clinical examination (OSCE), simulating the normal clinical practice. METHODS: As the goal of an OSCE presents the examination of clinical skills of medical students in a realistic setting, more than 100 students recruited from the university hospital of Cologne participated in either OSCE I or II. During the OSCE I intravenous cannulation was simulated while OSCE II simulated an acute abdominal pain station. Participants had to perform each of these stations under two circumstances: a normal simulated OSCE and an OSCE station with phone call distraction. Their performance during both simulations was then evaluated. RESULTS: In OSCE I students achieved significantly more points in the intravenous cannulation station if they were not distracted by phone calls (M=6.44 vs M=5.95). In OSCE II students achieved significantly more points in the acute abdominal pain station if they were not distracted by phone calls (M=7.59 vs M=6.84). While comparing only those students that completed both stations in OSCE I/II participating students achieved significantly more points in both OSCE I and II if they were not distracted by phone calls. CONCLUSION: The presented data shows that phone call distraction decreases the performance level of medical students during an OSCE station. Therefore, it is an indicator that distraction especially for younger doctors should be held to a minimum. On a second note distraction should be integrated in the medical education system as it plays an important role in clinical routine.

Nanoliposomal irinotecan in combination with leucovorin and 5-fluorouracil in advanced biliary tract cancers.

Biliary tract cancers (BTC) are rare but aggressive. Due to limited anti-tumor effects of current second- and later-line treatment regimens, novel treatment options are required. Nanoliposomal irinotecan in combination with leucovorin and 5-fluorouracil (FOLFnal-IRI) achieved promising results as a second-line treatment in patients with pancreatic cancer, warranting further investigation in BTC. In the present study, a retrospective analysis of patients receiving FOLFnal-IRI after initial platinum-based chemotherapy for advanced BTC between January 2016 and August 2020 at the University Hospital Cologne (Cologne, Germany) was performed. A total of 11 patients were identified who met the inclusion criteria. A total of 4 patients (36.4%) were female and the median age was 54 years. The proportion of patients suffering from gallbladder carcinoma, intrahepatic and extrahepatic cholangiocarcinoma was 18.2, 63.6 and 9.1%, respectively. Furthermore, 7 patients (63.6%) received FOLFnal-IRI as their second-, 3 (27.3%) as third- and one (9.1%) as their fourth-line therapy. The disease control rate was 54.5% and 3 grade III toxicities were recorded. Progression-free survival and overall survival (OS) after initiation of FOLFnal-IRI was 5.1 and 12.4 months, respectively. OS after initial diagnosis was 24.7 months. FOLFnal-IRI demonstrated promising antitumor potential with an acceptable safety profile as a subsequent therapy regimen in advanced biliary tract malignancies. Further randomized controlled trials of its value as a treatment option for BTC appear justified.

Kidney Transplantation After Rescue Allocation-the Eurotransplant Experience: A Retrospective Multicenter Outcome Analysis.

BACKGROUND: At Eurotransplant (ET), kidneys are transferred to "rescue allocation" (RA), whenever the standard allocation (SA) algorithms Eurotransplant Kidney Allocation System (ETKAS) and Eurotransplant Senior Program (ESP) fail. We analyzed the outcome of RA. METHODS: Retrospective patient clinical and demographic characteristics association analyses were performed with graft outcomes for 2422 recipients of a deceased donor renal transplantation (DDRT) after RA versus 25 481 after SA from 71 centers across all ET countries from 2006 to 2018. RESULTS: Numbers of DDRTs after RA increased over the time, especially in Germany. RA played a minor role in ESP versus ETKAS (2.7% versus 10.4%). RA recipients and donors were older compared with SA recipients and donors, cold ischemia times were longer, waiting times were shorter, and the incidence of primary nonfunction was comparable. Among ETKAS recipients, HLA matching was more favorable in SA (mean 3.7 versus 2.5). In multivariate modeling, the incidence of graft loss in ETKAS recipients was reduced in RA compared with SA (subdistribution hazard ratio, 0.80; 95% confidence interval [0.70-0.91], P < 0.001), whereas other outcomes (mortality, death with functioning graft (DwFG)) were not significantly different. None of the 3 outcomes were significantly different when comparing RA with SA within the ESP program. CONCLUSIONS: Facing increased waiting times and mortality on dialysis due to donor shortage, this study reveals encouragingly positive DDRT outcomes following RA. This supports the extension of RA to more patients and as an alternative tool to enable transplantation in patients in countries with prohibitively long waiting times or at risk of deterioration.

The rate of cholangiocarcinoma in Caroli Disease A German multicenter study.

BACKGROUND: Caroli Disease (CD) and Caroli Syndrome (CS) are rare disorders presenting with dilation of the intrahepatic bile ducts. CD/CS are associated with cholangiocarcinoma (CCA). However, the true incidence of CCA is still unclear, although it may serve as an indication for surgery. In this paper, we analyzed (I) the incidence of CCA in German centers, (II) reviewed our single center population together with its clinical presentation and (III) performed a thorough literature review. METHODS: 17 large HPB-centers across Germany were contacted and their patients after surgical treatment due to CD/CS with histopathology were included. Medline search for all studies published in English or German literature was performed. Patients who underwent surgery at our department between 2012 and 2020 due to CD or CS were analyzed. RESULTS: In the multicenter study, 79 patients suffered from CD and 119 patients from CS, with a total number of 198 patients. In 14 patients, CCA was found (Overall: 7,1%; CD: 6,3%, CS 7,6%). Between 2012 and 2020, 1661 liver resections were performed at our department. 14 patients underwent surgery due to CD or CS. Histological examination showed synchronous cholangiocarcinoma in one patient. The literature review revealed a CCA-rate of 7,3% in large series, whereas in case reports a rate of 6,8% was found. CONCLUSION: There is risk of malignant transformation and patients with CD might also benefit from resection due to improvement of symptoms. Therefore, resection is strongly advised. As certain patients with CS require transplantation, treatment should not be guided by the relatively low rate of CCA but by the concomitant diseases that come along with hepatic failure.

Gender benefit in laparoscopic surgical performance using a 3D-display system: data from a randomized cross-over trial.

BACKGROUND: The use of 3D technique compared to high-resolution 2D-4K-display technique has been shown to optimize spatial orientation and surgical performance in laparoscopic surgery. Since women make up an increasing amount of medical students and surgeons, this study was designed to investigate whether one gender has a greater benefit from using a 3D compared to a 4K-display system. METHODS: In a randomized cross-over trial, the surgical performance of male and female medical students (MS), non-board certified surgeons (NBCS), and board certified surgeons (BCS) was compared using 3D- vs. 4K-display technique at a minimally invasive training parkour with multiple surgical tasks and repetitions. RESULTS: 128 participants (56 women, 72 men) were included. Overall parkour time in seconds was 3D vs. 4K for all women 770.7 ± 31.9 vs. 1068.1 ± 50.0 (p < 0.001) and all men 664.5 ± 19.9 vs. 889.7 ± 31.2 (p < 0.001). Regarding overall mistakes, participants tend to commit less mistakes while using the 3D-vision system, showing 10.2 ± 1.1 vs. 13.3 ± 1.3 (p = 0.005) for all women and 9.6 ± 0.7 vs. 12.2 ± 1.0 (p = 0.001) for all men. The benefit of using a 3D system, measured by the difference in seconds, was for women 297.3 ± 41.8 (27.84%) vs. 225.2 ± 23.3 (25.31%) for men (p = 0.005). This can be confirmed in the MS group with 327.6 ± 65.5 (35.82%) vs. 249.8 ± 33.7 (32.12%), p = 0.041 and in the NBCS group 359 ± 52.4 (28.25%) vs. 198.2 ± 54.2 (18.62%), p = 0.003. There was no significant difference in the BCS group. CONCLUSION: 3D laparoscopic display technique optimizes surgical performance compared to the 2D-4K technique for both women and men. The greatest 3D benefit was found for women with less surgical experience. As a possible result of surgical education, this gender specific difference disappears with higher grade of experience. Using a 3D-vision system could facilitate surgical apprenticeship, especially for women.

Value of spectral detector computed tomography for the early assessment of technique efficacy after microwave ablation of hepatocellular carcinoma.

OBJECTIVES: To investigate whether virtual monoenergetic images (VMI) and iodine maps derived from spectral detector computed tomography (SDCT) improve early assessment of technique efficacy in patients who underwent microwave ablation (MWA) for hepatocellular carcinoma (HCC) in liver cirrhosis. METHODS: This retrospective study comprised 39 patients with 49 HCC lesions treated with MWA. Biphasic SDCT was performed 7.7±4.0 days after ablation. Conventional images (CI), VMI and IM were reconstructed. Signal- and contrast-to-noise ratio (SNR, CNR) in the ablation zone (AZ), hyperemic rim (HR) and liver parenchyma were calculated using regions-of-interest analysis and compared between CI and VMI between 40-100 keV. Iodine concentration and perfusion ratio of HR and residual tumor (RT) were measured. Two readers evaluated subjective contrast of AZ and HR, technique efficacy (complete vs. incomplete ablation) and diagnostic confidence at determining technique efficacy. RESULTS: Attenuation of liver parenchyma, HR and RT, SNR of liver parenchyma and HR, CNR of AZ and HR were significantly higher in low-keV VMI compared to CI (all p<0.05). Iodine concentration and perfusion ratio differed significantly between HR and RT (all p<0.05; e.g. iodine concentration, 1.6±0.5 vs. 2.7±1.3 mg/ml). VMI50keV improved subjective AZ-to-liver contrast, HR-to-liver contrast, visualization of AZ margin and vessels adjacent to AZ compared to CI (all p<0.05). Diagnostic accuracy for detection of incomplete ablation was slightly higher in VMI50keV compared to CI (0.92 vs. 0.89), while diagnostic confidence was significantly higher in VMI50keV (p<0.05). CONCLUSIONS: Spectral detector computed tomography derived low-keV virtual monoenergetic images and iodine maps provide superior early assessment of technique efficacy of MWA in HCC compared to CI.

Hand-Assisted Retroperitoneoscopic Donor Nephrectomy Compared to Anterior Approach Open Donor Nephrectomy: Improved Long-Term Physical Component Score in Health-Related Quality of Life in Living Kidney Donors.

BACKGROUND: Health-related quality of life (HRQL), fatigue, anxiety, and depression are crucial for the living kidney donor (LKD). Follow-up data for HRQL of LKDs comparing surgical techniques, especially regarding hand-assisted retroperitoneoscopic donor nephrectomy (HARP), are sparse. The aim of this study was to evaluate the influence of abdominal wall trauma minimized by HARP in comparison to open anterior approach donor nephrectomy (AA) on HRQL and additional psychosocial aspects of LKDs during the long-term follow-up. MATERIAL AND METHODS: This is a cross-sectional study comparing psychosocial aspects of LKD between HARP and AA. RESULTS: This study included 100 LKDs (68 HARP, 28 AA, and 4 were excluded secondary to incomplete data). The time to follow-up was 22.6 ± 11.7 (HARP) vs 58.7 ± 13.9 (AA) months (P < .005). Complications ≥3a° due to Clavien-Dindo classification was 0% in both groups. There were higher scores in all physical aspects for HARP donors vs AA donors at that time (physical function: 89.8 ± 14.6 vs 80.0 ± 19.9, P = .008, and the physical component score: 53.9 ± 7.6 vs 48.6 ± 8.5, P = .006). One year later (follow-up time + 12 months), HRQL for HARP donors was still higher. Mental items showed no significant differences. HARP donors showed better physical scores compared to the age-matched nondonor population (AA donors had lower scores). Neither the Multidimensional Fatigue Inventory-20 (MFI-20) or the Hospital Anxiety and Depression Scale (HADS) showed any differences between the 2 groups. Fatigue scores were higher for HARP and for AA compared to the age-matched population. CONCLUSIONS: LKDs undergoing HARP showed better physical performance as part of HRQL in the long-term follow-up.

Learning curve of surgical novices using the single-port platform SymphonX: minimizing OR trauma to only one 15-mm incision.

BACKGROUND: Minimally invasive single-port surgery is always associated with large incisions up to 2-3 cm, complicated handling due to the lack of triangulation, and instrument crossing. The aim of this prospective study was to report how medical students without any laparoscopic experience perform several laparoscopic tasks (rope pass, paper cut, peg transfer, recapping, and needle threading) with the new SymphonX single-port platform and to examine the learning curves in comparison to the laparoscopic multi-port technique. METHODS: A set of 5 laparoscopic skill tests (Rope Pass, Paper cut, Peg Transfer, Recapping, Needle Thread) were performed with 3 repetitions. Medical students performed all tests with both standard laparoscopic instruments and the new platform. Time and errors were recorded. RESULTS: A total of 114 medical students (61 females) with a median age of 23 years completed the study. All subjects were able to perform the skill tests with both standard laparoscopic multi-port and the single-port laparoscopic system and were able to significantly improve their performance over the three trials for all five tasks-rope pass (p < 0.001), paper cut (p < 0.001), peg transfer (p < 0.001), needle threading (p < 0.001), and recapping (p < 0.001). In 3 out of 5 tasks, medical students performed the tasks faster using the standard multi-port system-rope pass (p < 0.001), paper cut (p < 0.001), and peg transfer (p < 0.001). In the task recapping, medical students performed the task faster using the new single-port system (p = 0.003). In the task needle threading, there was no significant difference between the standard multi-port system and the new single-port system (p > 0.05). CONCLUSION: This is the first study analyzing learning curves of the commercially available SymphonX platform for abdominal laparoscopic surgery when used by novices. The learning curve and the error rate are promising.

Microwave ablation enhances tumor-specific immune response in patients with hepatocellular carcinoma.

Thermal ablative therapies are standard treatments for localized hepatocellular carcinoma (HCC). In addition to local tumor destruction, ablation leads to abscopal effects in distant lesions most likely mediated by an anti-tumor immune response. Although microwave ablation (MWA) is increasingly substituting other ablative techniques, its systemic immunostimulatory effects are poorly studied. We analyzed tumor-specific immune responses in peripheral blood of HCC patients after thermal ablation with regard to T cell responses and disease outcome. While comprehensive flow cytometric analyses in sequential samples of a prospective patient cohort (n = 23) demonstrated only moderate effects of MWA on circulating immune cell subsets, fluorospot analyses of specific T cell responses against seven tumor-associated antigens (TTAs) revealed de-novo or enhanced tumor-specific immune responses in 30% of patients. This anti-tumor immune response was related to tumor control as Interferon-y and Interleukin-5 T cell responses against TAAs were more frequent in patients with a long-time remission (> 1 year) after MWA (7/16) compared to patients suffering from an early relapse (0/13 patients) and presence of tumor-specific T cell response (IFN-y and/or IL-5) was associated to longer progression-free survival (27.5 vs. 10.0 months). Digital image analysis of immunohistochemically stained archival HCC samples (n = 18) of patients receiving combined MWA and resection revealed a superior disease-free survival of patients with high T cell abundance at the time of thermal ablation (37.4 vs. 13.1 months). Our data demonstrates remarkable immune-related effects of MWA in HCC patients and provides additional evidence for a combination of local ablation and immunotherapy in this challenging disease.

The proteomic landscape of small urinary extracellular vesicles during kidney transplantation.

Kidney transplantation is the preferred renal replacement therapy available. Yet, long-term transplant survival is unsatisfactory, partially due to insufficient possibilities of longitudinal monitoring and understanding of the biological processes after transplantation. Small urinary extracellular vesicles (suEVs) - as a non-invasive source of information - were collected from 22 living donors and recipients. Unbiased proteomic analysis revealed temporal patterns of suEV protein signature and cellular processes involved in both early response and longer-term graft adaptation. Complement activation was among the most dynamically regulated components. This unique atlas of the suEV proteome is provided through an online repository allowing dynamic interrogation by the user. Additionally, a correlative analysis identified putative prognostic markers of future allograft function. One of these markers - phosphoenol pyruvate carboxykinase (PCK2) - could be confirmed using targeted MS in an independent validation cohort of 22 additional patients. This study sheds light on the impact of kidney transplantation on urinary extracellular vesicle content and allows the first deduction of early molecular processes in transplant biology. Beyond that our data highlight the potential of suEVs as a source of biomarkers in this setting.