Publications by authors named "Roland S Croner"

77 Publications

Transcriptome-Wide Analysis of Human Liver Reveals Age-Related Differences in the Expression of Select Functional Gene Clusters and Evidence for a PPP1R10-Governed 'Aging Cascade'.

Pharmaceutics 2021 Nov 25;13(12). Epub 2021 Nov 25.

Department of Medicine, University Hospital Knappschaftskrankenhaus Bochum, Ruhr University Bochum, 44892 Bochum, Germany.

A transcriptome-wide analysis of human liver for demonstrating differences between young and old humans has not yet been performed. However, identifying major age-related alterations in hepatic gene expression may pinpoint ontogenetic shifts with important hepatic and systemic consequences, provide novel pharmacogenetic information, offer clues to efficiently counteract symptoms of old age, and improve the overarching understanding of individual decline. Next-generation sequencing (NGS) data analyzed by the Mann-Whitney nonparametric test and Ensemble Feature Selection (EFS) bioinformatics identified 44 transcripts among 60,617 total and 19,986 protein-encoding transcripts that significantly ( = 0.0003 to 0.0464) and strikingly (EFS score > 0.3:16 transcripts; EFS score > 0.2:28 transcripts) differ between young and old livers. Most of these age-related transcripts were assigned to the categories 'regulome', 'inflammaging', 'regeneration', and 'pharmacogenes'. NGS results were confirmed by quantitative real-time polymerase chain reaction. Our results have important implications for the areas of ontogeny/aging and the age-dependent increase in major liver diseases. Finally, we present a broadly substantiated and testable hypothesis on a genetically governed 'aging cascade', wherein acts as a putative ontogenetic master regulator, prominently flanked by and . This transcriptome-wide analysis of human liver offers potential clues towards developing safer and improved therapeutic interventions against major liver diseases and increased insights into key mechanisms underlying aging.
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http://dx.doi.org/10.3390/pharmaceutics13122009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8709089PMC
November 2021

Three-Device (3D) Technique for Liver Parenchyma Dissection in Robotic Liver Surgery.

J Clin Med 2021 Nov 12;10(22). Epub 2021 Nov 12.

University Clinic for General, Visceral, Vascular and Transplant Surgery, University of Magdeburg, Leipzigerstr. 44, 39120 Magdeburg, Germany.

Background: The implementation of robotics in liver surgery offers several advantages compared to conventional open and laparoscopic techniques. One major advantage is the enhanced degree of freedom at the tip of the robotic tools compared to laparoscopic instruments. This enables excellent vessel control during inflow and outflow dissection of the liver. Parenchymal transection remains the most challenging part during robotic liver resection because currently available robotic instruments for parenchymal transection have several limitations and there is no standardized technique as of yet. We established a new strategy and share our experience.

Methods: We present a novel technique for the transection of liver parenchyma during robotic surgery, using three devices (3D) simultaneously: monopolar scissors and bipolar Maryland forceps of the robot and laparoscopic-guided waterjet. We collected the perioperative data of twenty-eight patients who underwent this procedure for minor and major liver resections between February 2019 and December 2020 from the Magdeburg Registry of minimally invasive liver surgery (MD-MILS).

Results: Twenty-eight patients underwent robotic-assisted 3D parenchyma dissection within the investigation period. Twelve cases of major and sixteen cases of minor hepatectomy for malignant and non-malignant cases were performed. Operative time for major liver resections (≥ 3 liver segments) was 381.7 (SD 80.6) min vs. 252.0 (70.4) min for minor resections ( < 0.01). Intraoperative measured blood loss was 495.8 (SD 508.8) ml for major and 256.3 (170.2) ml for minor liver resections ( = 0.090). The mean postoperative stay was 13.3 (SD 11.1) days for all cases. Liver surgery-related morbidity was 10.7%, no mortalities occurred. We achieved an R0 resection in all malignant cases.

Conclusions: The 3D technique for parenchyma dissection in robotic liver surgery is a safe and feasible procedure. This novel method offers an advanced locally controlled preparation of intrahepatic vessels and bile ducts. The combination of precise extrahepatic vessel handling with the 3D technique of parenchyma dissection is a fundamental step forward to the standardization of robotic liver surgery for teaching purposing and the wider adoption of robotic hepatectomy into routine patient care.
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http://dx.doi.org/10.3390/jcm10225265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8653962PMC
November 2021

Long-Term Follow-Up of Patients Receiving Neoadjuvant Treatment Modalties for Soft Tissue Sarcomas of the Extremities.

Cancers (Basel) 2021 Oct 19;13(20). Epub 2021 Oct 19.

Department of Surgery, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.

Background: Neoadjuvant treatment modalities in soft tissue sarcoma (STS) of the extremities have become more popular in recent years, but because of the rarity and heterogeneity of STS, there are yet few studies on the long-term impact of neoadjuvant treatment modalities, especially in terms of neoadjuvant radiochemotherapy.

Methods: The study enrolled 136 patients with primary STS of the extremities who underwent surgery with curative intent or neoadjuvant therapy, followed by surgery in a 15-year period. Neoadjuvant treatment consisted of radiotherapy (RT) with 60 Gy and in most cases simultaneous chemotherapy (CTx) with ifosfamide (1.5 g/m/d, d1-5, q28) and doxorubicine (50 mg/m/d, d3, q28). We investigated the clinical, (post)-operative and histopathological data and the oncological follow-up as well. The median follow-up period was 82 months (range 6-202).

Results: A total of 136 patients (M:F = 73:63) with a mean age of 62 years (range; 21-93) was observed. Seventy-four patients (54.4%) received neoadjuvant therapy (NT), 62 patients (45.6%) received primary surgery (PS). When receiving NT, patients with high-risk STS had a lower risk to develop distant metastasis ( = 0.025). Age, histological type, tumor size and surgical margins (R0 vs. R1) had no influence on any survival rates. There was an association between NT and the occurrence of postoperative complications ( = 0.001). The 5-year local recurrence free survival (LRFS), metastasis free survival (MFS), disease free survival (DFS) and overall survival (OS) rate of the whole cohort was 89.9%, 77.0%, 70.6% and 72.6%; whereas the 5-year LRFS, MFS, DFS and OS rate was 90.5%, 67.2%, 64.1% and 62.8% for the NT group and 89.5%, 88.3%. 78.4% and 83.8% for the PS group.

Conclusions: Multimodal treatment strategies in patients with STS of extremities lead to excellent oncological outcomes. Patients with high-risk STS had a significantly better MFS when receiving NT than patients with low-risk STS. NT was associated with a higher probability of postoperative but well-manageable complications.
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http://dx.doi.org/10.3390/cancers13205244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534061PMC
October 2021

Surgical Approaches and Oncological Outcomes in the Management of Duodenal Gastrointestinal Stromal Tumors (GIST).

J Clin Med 2021 Sep 28;10(19). Epub 2021 Sep 28.

Department of Surgery, University Hospital Magdeburg, 39106 Magdeburg, Germany.

Background: Duodenal gastrointestinal stromal tumors (GIST) are a rare subset of GIST. Their surgical management in this anatomically complex region consists of varied approaches, and the administration of imatinib mesylate (IM) has not been clarified.

Methods: We retrospectively reviewed patients with duodenal GIST treated during a 10-year-period. We analysed the clinicopathological characteristics and survival factors and evaluated the perioperative and long-term outcomes based on the extent of resection ((ocal-resection (LR) versus pancreaticoduodenectomy (PD)) and the IM-administration. The median follow-up period was 60 months (range, 12-140).

Results: A total of thirteen patients (M:F = 7:6) with median age of 64 years (range, 42-77) underwent resection of duodenal GIST. Median tumor size was 5.2 cm (range, 1.5-13.3). Eight patients (61.5%) underwent LR and five patients (38.5%) PD. R0-resection was achieved in 92.5%. Neoadjuvant IM-therapy was administered in five patients leading to tumor downsizing and in 40% to less-extended resection. The PD group consisted of larger tumors with higher mitotic count, mostly located in D2 ( = 0.031). The PD group had longer operative time ( = 0.026), longer hospital stay ( = 0.016), and higher rate of postoperative complications ( = 0.128). The actuarial 1-, 3-, and 5-year overall survival were 92.5%, 84%, and 73.5%, respectively, whereas the disease-free survival rates at 1, 3, and 5 years were 91.5%, 83%, and 72%, respectively. A tendency towards increased risk of disease recurrence was demonstrated for patients with tumor >5 cm and high-risk potential. There was not statistic survival benefit for one or the other surgical approach.

Conclusion: The type of resection depends on duodenal site of origin and tumor size. LR can be the treatment of choice for duodenal GIST whenever technically feasible. Recurrence of duodenal GIST is dependent on tumor biology rather than surgical approach. Administration of IM in neaodjuvant setting should be considered in cases with high-risk GIST scheduled for PD since it might facilitate less-extended resection.
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http://dx.doi.org/10.3390/jcm10194459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509470PMC
September 2021

Diffuse Neuromatosis of Intrahepatic and Extrahepatic Bile Ducts as a Rare Cause of Jaundice.

Visc Med 2021 Jun 30;37(3):226-232. Epub 2020 Sep 30.

Department of Pathology, University Hospital Erlangen, Erlangen, Germany.

Background: Neuroma of the biliary tree is extremely rare with no more than 100 cases reported so far. They mostly present with obstructive jaundice and have been commonly described after surgery or abdominal trauma. Although involvement of the extrahepatic bile duct is far more common, occurrence in the intrahepatic ducts has not so far been reported.

Case Report: We describe 3 cases of diffuse biliary tree neuroma affecting 3 females aged 53-68 years. None had a history of neurofibromatosis type1. All presented with progressive obstructive jaundice with no evidence of gallstones. A history of previous surgery was noted in 2 patients. Initial impression on clinical and imaging examination was highly suspicious for bile duct carcinoma in 2 patients. Histology showed diffuse neuromatous proliferation replacing and thickening the bile duct walls. The third patient had concurrent neuroma and recurrent cholangiocarcinoma causing great clinical confusion as initial biopsy showed only benign neuroma, but CA 19-9 was steadily increasing, necessitating a second biopsy which then confirmed recurrent carcinoma.

Conclusion: This uncommon cause of long-distance bile duct stenosis and progressive jaundice should be included in the differential diagnosis of bile duct neoplasms, in particular when there is a previous surgical history in this abdominal region.
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http://dx.doi.org/10.1159/000510486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237796PMC
June 2021

Incisional hernia after liver transplantation: mesh-based repair and what else?

Surg Today 2021 May 16;51(5):733-737. Epub 2020 Oct 16.

Department of Surgery, University Hospital Erlangen, University of Erlangen-Nuremberg, Erlangen, Germany.

Purpose: Incisional hernia (IH) is not uncommon after liver transplantation (LT). We investigated the long-term outcome of mesh-based hernia repair using an inlay-onlay technique.

Methods: Our analysis was based on a prospective collected database of all LT recipients from our hospital over a period of 15 years. We analyzed clinical data including the period between LT and hernia development, the size and localization of the hernia, the length of in-hospital stay, immunosuppression, and postoperative morbidity, as well as follow-up data. The median follow-up period was 120 (range 12-200) months.

Results: Among a total of 220 patients who underwent a collective 239 LTs, 29 (13%) were found to have an IH after a median period of 27.5 months (range 3-96 months). There were 12 (41%) men and 17 (59%) women, with a median age of 51 years. The median size of the IH was 13 cm (range 2-30 cm) and the median in-hospital stay was 6 days. Mild postoperative complications developed in seven patients, including two onlay mesh infections. One patient (3.4%) suffered recurrence.

Conclusion: Mesh-based hernia repair using the inlay/onlay technique represents an effective and safe method for patients with an IH after LT, without additional risk from continuous immunosuppression.
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http://dx.doi.org/10.1007/s00595-020-02162-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055617PMC
May 2021

Multimodale Therapie primärer, nicht metastasierter retroperitonealer Sarkome.

Zentralbl Chir 2020 Oct 7;145(5):405-416. Epub 2020 Oct 7.

Universitätsklinik für Allgemein-, Viszeral-, Gefäß- und Transplantationschirurgie, Otto-von-Guericke-Universität Magdeburg, Deutschland.

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http://dx.doi.org/10.1055/a-1132-3760DOI Listing
October 2020

Advanced Pancreatic Ductal Adenocarcinoma: Moving Forward.

Cancers (Basel) 2020 Jul 18;12(7). Epub 2020 Jul 18.

Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, 39120 Magdeburg, Germany.

Globally, the death rate of pancreatic ductal adenocarcinoma (PDAC) has doubled over 30 years and is likely to further increase, making PDAC a leading cause of cancer-related death in the coming years. PDAC is typically diagnosed at an advanced stage, and modified FOLFIRINOX or nab-paclitaxel and gemcitabine are the mainstay of systemic therapy. For elderly patients with good performance status, low-dose treatment can preserve quality of life without compromising cancer control or survival. Maintenance therapy should be considered in PDAC patients achieving disease control with systemic therapy. In particular, olaparib has demonstrated a progression-free survival benefit of 3.6 months in a subgroup of PDAC patients with germline BRCA1/2 mutations (ca. 10% of all PDAC). Pancreatic enzyme replacement therapy is often omitted in the treatment of patients with PDAC, with possibly deleterious consequences. Small intestinal bacterial overgrowth is highly prevalent in patients with PDAC and should be considered in the diagnostic algorithm of PDAC patients with bloating and diarrhea. Rivaroxaban has been associated with a reduced risk of thrombosis without an increase in major bleeding events, and its use should be considered in every patient with advanced PDAC undergoing systemic therapy.
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http://dx.doi.org/10.3390/cancers12071955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409054PMC
July 2020

Liver Transplant Due to Flupirtine-Induced Acute Liver Failure.

Exp Clin Transplant 2020 08 6;18(4):481-484. Epub 2020 Jul 6.

From the Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena, Germany.

Objectives: Acute drug-induced liver failure is a rare indication for liver transplant. There is only one case of flupirtine-induced liver failure requiring transplant in the literature. In February 2018, the European Medicines Agency issued a withdrawal of approval for flupirtine medication in European countries as a result of the risk of acute liver failure.

Materials And Methods: The aim of this study was a German-wide collection of data regarding patients with liver transplant as a result of flupirtine-associated liver failure.

Results: A total of 9 patients received transplants. All patients were women with a mean age of 43 years. Indication for flupirtine medication was musculoskeletal symptoms and migraine headache. The medication was taken over a period of approximately 3 months. All patients developed progressive acute liver failure, and no patient had previous chronic liver disease or cirrhosis. The mean laboratory Model for End Stage Liver Disease score for the patients was 31 ± 7 at time of transplant. Eight of the 9 patients were listed as "high urgency" for transplant. After transplant, they had an uneventful course with a prolonged mean intensive care unit stay of 13 ± 8.7 days. The whole hospitalization time was 43 ± 21 days.

Conclusions: This is the largest published series of patients who received liver transplant after a drug-induced acute liver failure from flupirtine medication.
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http://dx.doi.org/10.6002/ect.2019.0297DOI Listing
August 2020

[Magdeburg Medical School - Logbook for Surgical Training of Final Year Medical Students - an Interdisciplinary, Medical School-Specific Concept Based on the Guidelines Issued by the Medical School Association ("Medizinischer Fakultätentag") in 2012].

Zentralbl Chir 2020 Dec 8;145(6):549-558. Epub 2020 Apr 8.

Klinik für Allgemein-, Viszeral-, Gefäß- und Transplantationschirurgie, Universitätsklinikum Magdeburg A. ö. R., Deutschland.

Background: The final year is the last part of the study of human medicine and can be regarded as an essential period, during which medical knowledge should be consequently converted into medical expertise. Since the amendment of the medical license policy ("Ärztliche Approbationsordnung" [ÄApprO]) from July 17, 2012, in particular, since April 01, 2013, German universities have been obliged to provide a training schedule such as a "logbook" for this final year, specifically for the mandatory time periods within surgery and internal medicine. In preparation for this innovation, the German Medical School Association ("Medizinischer Fakultätentag") presented basic logbooks as consensus documents in June 2012. The portfolio for each surgery discipline and the Magdeburg Medical School, had been developed on the basis of individual initiatives and used for years, and was revised, specified and further developed into a "logbook of the medical study's final year" - specific for daily practice and the Magdeburg Medical School, and to the guidelines of the Medical School Association ("Medizinischer Fakultätentag"). The aim of the present commentary is i) to present the Magdeburg Medical School logbook and its clinical planning for cases, diagnoses and (surgical) interventions, as a summary of institutional experience and ii) to describe the mandatory surgical part of the "Magdeburg's final year of the study of human medicine".

Method: Narrative short overview including individual teaching experiences and topic-related references from "PubMed" using terms for literature search such as "surgical logbook", "practical year" and "medical teaching". The background and aims of the document's modifications are explained for each surgical discipline.

Results: The "Logbook" is subdivided into 6 chapters: introduction, basics, statement of requirement, selected surgical diseases and interventions as well as information on final year-associated events and courses and instructions for creating the obligatory case report.

Conclusion: The presented "Magdeburg Medical School Final Year Logbook of the Surgical Disciplines" has been created according to the requirements of the German Medical School Association ("Medizinischer Fakultätentag") and has been simultaneously adapted to the conditions and established medical teaching at the presenting Medical School. In particular, the medical students are given a document related to daily clinical practice, which allows them, within an overall teaching concept, to acquire indispensable expertise.
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http://dx.doi.org/10.1055/a-1084-4127DOI Listing
December 2020

[Neoadjuvant radiotherapy improves overall survival and disease-free interval in resectable hepatocellular carcinoma with portal vein tumor thrombosis].

Strahlenther Onkol 2020 Feb;196(2):194-196

Department of General and Visceral Surgery, University Medical Center Magdeburg, Magdeburg, Deutschland.

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http://dx.doi.org/10.1007/s00066-019-01570-2DOI Listing
February 2020

Introduction of complete mesocolic excision with central vascular ligation as standardized surgical treatment for colon cancer in Greece. Results of a pilot study and bi-institutional cooperation.

Arch Med Sci 2019 Sep 29;15(5):1269-1277. Epub 2018 Nov 29.

Department of Surgery, University Hospital Erlangen, Erlangen, Germany.

Introduction: Complete mesocolic excision (CME) is generally accepted as state of the art in colon cancer surgery. However, the long-term impact of CME has not been systematically examined. Therefore cohort studies might be a possible way to clarify any differences between conventional resections and CME. Following bilateral cooperation between the Department of Surgery/University Hospital of Erlangen and the 1 Surgical Department of the General Hospital of Nikaia/Piraeus, including teaching activities for introduction of CME, a cohort study was performed, considering surgical quality criteria and clinical outcome.

Material And Methods: All patients with colon carcinomas (CME group, = 31) referred to the 1 Surgical Department of General Hospital, Nikaia/Piraeus, Greece for surgery from January 2012 to December 2013 were prospectively analyzed and compared with patients who underwent conventional surgery for colon cancer between January 2008 and December 2011 (non-CME group, = 35). Patients' follow-up was at least 48 months.

Results: There were significantly better results in terms of lymph node yield (CME group: 29.6 vs. non-CME group: 17.85; < 0.001) and lymph node ratio (LNR) (CME group: 0.12 vs. non-CME group: 0.24; < 0.001) and recurrence-free survival in favor of the CME group (CME group: = 0 vs. non-CME group: = 5) without any increase in surgical morbidity (CME group: = 6 vs. non-CME group: = 11; = 0.10).

Conclusions: Complete mesocolic excision appears to offer a superior oncological result without any increase of postoperative morbidity and mortality. Furthermore, CME represents a surgical technique which can be established in a surgical department after previous teaching without increasing the postoperative complication rate.
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http://dx.doi.org/10.5114/aoms.2018.80040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764310PMC
September 2019

β -integrin serves as a novel serum tumor marker for colorectal carcinoma.

Int J Cancer 2019 08 29;145(3):678-685. Epub 2019 Jan 29.

Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide and the need for novel biomarkers and therapeutic strategies to improve diagnosis and surveillance is obvious. This study aims to identify β -integrin (ITGB6) as a novel serum tumor marker for diagnosis, prognosis, and surveillance of CRC. ITGB6 serum levels were validated in retro- and prospective CRC patient cohorts. ITGB6 serum levels were analyzed by ELISA. Using an initial cohort of 60 CRC patients, we found that ITGB6 is present in the serum of CRC, but not in non-CRC control patients. A cut-off of ≥2 ng/mL ITGB6 reveals 100% specificity for the presence of metastatic CRC. In an enlarged study cohort of 269 CRC patients, ITGB6 predicted the onset of metastatic disease and was associated with poor prognosis. Those data were confirmed in an independent, prospective cohort consisting of 40 CRC patients. To investigate whether ITGB6 can also be used for tumor surveillance, serum ITGB6-levels were assessed in 26 CRC patients, pre- and post-surgery, as well as during follow-up visits. After complete tumor resection, ITGB6 serum levels declined completely. During follow-up, a new rise in ITGB6 serum levels indicated tumor recurrence or the onset of new metastasis as confirmed by CT scan. ITGB6 was more accurate for prognosis of advanced CRC and for tumor surveillance as the established marker carcinoembryonic antigen (CEA). Our findings identify ITGB6 as a novel serum marker for diagnosis, prognosis, and surveillance of advanced CRC. This might essentially contribute to an optimized patient care.
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http://dx.doi.org/10.1002/ijc.32137DOI Listing
August 2019

Perioperative Systemic Chemotherapy, Cytoreductive Surgery, and Hyperthermic Intraperitoneal Chemotherapy in Patients With Colorectal Peritoneal Metastasis: Results of the Prospective Multicenter Phase 2 COMBATAC Trial.

Clin Colorectal Cancer 2018 12 31;17(4):285-296. Epub 2018 Jul 31.

Department of Surgery, University Medical Center Regensburg, Regensburg, Germany; Department of Surgery, Krankenhaus Barmherzige Brüder Regensburg, Regensburg, Germany.

Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as parts of an interdisciplinary treatment concept including systemic chemotherapy can improve survival of selected patients with peritoneal metastatic colorectal cancer (pmCRC). Nevertheless, the sequence of the therapeutic options is still a matter of debate. Thus, the COMBATAC (COMBined Anticancer Treatment of Advanced Colorectal cancer) trial was conducted to evaluate a combined treatment regimen consisting of preoperative systemic polychemotherapy + cetuximab followed by CRS + HIPEC and postoperative systemic polychemotherapy + cetuximab.

Patients And Methods: The COMBATAC trial is a prospective, multicenter, open-label, single-arm, single-stage phase 2 trial. Twenty-six patients with synchronous or metachronous colorectal or appendiceal peritoneal carcinomatosis were included. Enrollment was terminated prematurely by the sponsor because of slow recruitment. Progression-free survival as primary end point and overall survival were estimated by the Kaplan-Meier method. Also evaluated were morbidity according to Common Terminology Criteria for Adverse Events v4.0 and feasibility of the combined treatment concept.

Results: Median progression-free survival for the intention-to-treat population (n = 25) was 14.9 months. Median overall survival was not reached during the study duration. Ninety-two adverse events were documented in 16 patients, including 14 serious adverse events in 9 patients. The overall morbidity rate was 64%, and the grade 3/4 morbidity rate was 44%. Of all grade 3/4 morbidity events, 36.4% were related to systemic chemotherapy and 22.7% to surgery, whereas 40.9% were not directly related. There was no treatment-related mortality.

Conclusion: The results of the COMBATAC trial show that the multimodal treatment concept consisting of perioperative systemic chemotherapy and CRS + HIPEC is safe and feasible. Progression-free survival in selected patients with colorectal or appendiceal peritoneal metastasis might be improved.
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http://dx.doi.org/10.1016/j.clcc.2018.07.011DOI Listing
December 2018

Gastrointestinal schwannomas: a rare but important differential diagnosis of mesenchymal tumors of gastrointestinal tract.

BMC Surg 2018 Jul 25;18(1):47. Epub 2018 Jul 25.

Department of Surgery, University Hospital Erlangen, Krankenhausstrasse 12, 91054, Erlangen, Germany.

Background: Schwannomas of gastrointestinal tract are rare, mostly benign and notably different neoplasms from conventional schwannomas that arise in soft tissue or the central nervous system. These tumors are of clinical importance since they should always be considered in the differential diagnosis of submucosal lesions of gastrointestinal tract.

Methods: Seven patients with a pathologically proven gastrointestinal schwannoma were identified in our series of mesenchymal tumors and reviewed retrospectively. Clinicopathological and immunohistochemical parameters along with the follow-up results were analysed.

Results: The series included two males and five females, with a mean age 69 years (range, 39-81). Most patients were asymptomatic on presentation, except for two patients with abdominal pain. In the other cases (n = 5), the tumor was an incidental finding during other medical, imaging or surgical procedures. The tumors were located in the stomach (n = 4) and in the small intestine (n = 3) with an average size of 29 mm (range, 12-70). A preoperative diagnosis was achieved only in one case with a CT-guided core biopsy. Otherwise the clinical, intraoperative, endoscopic or radiological findings were unspecific. Patients with gastric tumor underwent either laparoscopic (n = 2) or open (n = 2) gastric wedge resection of the tumor; in the cases of intestinal tumor (n = 3) a segmentectomy was performed. Pathological examination revealed solid homogenous tumors, which were highly cellular and composed of spindle cells with positive staining for S100 protein, and confirmed the diagnosis of schwannoma. All tumors were negative for c-Kit, smooth muscle actin, desmin and DOG-1 and showed very low proliferation index. There were negative resection margins and no malignant variants were recognized. At an average follow-up of 60 months (range, 24-185) all patients were free of disease with no signs of recurrence or metastases and acceptable gastrointestinal function.

Conclusions: Schwannomas are rare, slow-growing and mostly asymptomatic gastrointestinal mesenchymal tumors. They are difficult to be diagnosed preoperatively as endoscopic and radiological findings are nonspecific but histological and immunohistochemical features are of paramount importance to differentiate between benign and malignant schwannomas, or other spindle cell sarcomas. The treatment of choice is complete surgical excision without a conclusive preoperative diagnosis, and the long-term outcome is excellent as these lesions are mostly benign.
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http://dx.doi.org/10.1186/s12893-018-0379-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6060462PMC
July 2018

Implementing complete mesocolic excision for colon cancer - mission completed?

Innov Surg Sci 2018 Mar 10;3(1):17-29. Epub 2018 Feb 10.

Department of Surgery, University Hospital Erlangen, Erlangen, Germany.

The definition of complete mesocolic excision (CME) for colon carcinomas revolutionized the way of colon surgery. This technique conquered the world starting from Erlangen. Nevertheless, currently new developments especially in minimally invasive surgery challenge CME to become settled as a standard of care. To understand the evolution of CME, anatomical details occurring during embryogenesis and their variations have to be considered. This knowledge is indispensable to transfer CME from an open to a minimally invasive setting. Conventional surgery for colon cancer (non-CME) has a morbidity of 12.1-28.5% and a 3.7% mortality risk vs. 12-36.4% morbidity and 2.1-3% mortality for open CME. The morbidity of laparoscopic CME is between 4 and 31% with a mortality of 0.5-0.9%. In robotic assisted surgery, morbidity between 10 and 25% with a mortality of 1% was published. The cancer-related survival after 3 and 5 years for open CME is respectively 91.3-95% and 90% vs. 87% and 74% for non-CME. For laparoscopic CME the 3- and 5-year cancer-related survival is 87.8-97% and 79.5-80.2%. In stage UICC III the 3- and 5-year cancer-related survival is 83.9% and 80.8% in the Erlangen data of open technique vs. 75.4% and 65.5-71.7% for laparoscopic surgery. For stage UICC III the 3- and 5-year local tumor recurrence is 3.8%. The published data and the results from Erlangen demonstrate that CME is safe in experienced hands with no increased morbidity. It offers an obvious survival benefit for the patients which can be achieved solely by surgery. Teaching programs are needed for minimally invasive CME to facilitate this technique in the same quality compared to open surgery. Passing these challenges CME will become the standard of care for patients with colon carcinomas offering all benefits of minimally invasive surgery and oncological outcome.
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http://dx.doi.org/10.1515/iss-2017-0042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754049PMC
March 2018

What is Changing in Indications and Treatment of Focal Nodular Hyperplasia of the Liver. Is There Any Place for Surgery?

Ann Hepatol 2017 May - Jun;16(3):333-341

Department of Surgery, University of Erlangen-Nuremberg, Krankenhausstr. Erlangen, Germany.

Focal nodular hyperplasia (FNH) is a common benign liver tumor, which occurs in the vast majority of the cases in young women. FNH represents a polyclonal lesion characterized by local vascular abnormalities and is a truly benign lesion without any potential for malignant transformation. A retrospective single institution analysis of 227 FNH patients, treated from 1990 to 2016 and a review of studies reporting surgical therapy of overall 293 patients with FNH was performed. Indications for resection with a focus on diagnostic workup, patient selection, surgical mode and operative mortality and morbidity have been analysed. Ninety three patients underwent elective hepatectomy and 134 patients observation alone, where median follow-up was 107 months. Postoperative complications were recorded in 14 patients, 92% of patients reported an improvement with respect to their symptoms. Overall among 293 patients underwent surgery in the series, included to this review, there was a morbidity of 13%, where median follow-up was 53 months. Systematic follow-up remains the gold standard in asymptomatic patients with FNH. However elective surgery should be considered in symptomatic patients, in those with marked enlargement and in case of uncertainty of diagnosis. Surgery for FNH is a safe procedure with low morbidity and very good long term results as far as quality of life after surgery is concerned and surely an integral part of the modern management of FNH.
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http://dx.doi.org/10.5604/16652681.1235475DOI Listing
October 2017

Matricellular protein SPARCL1 regulates tumor microenvironment-dependent endothelial cell heterogeneity in colorectal carcinoma.

J Clin Invest 2016 11 10;126(11):4187-4204. Epub 2016 Oct 10.

Different tumor microenvironments (TMEs) induce stromal cell plasticity that affects tumorigenesis. The impact of TME-dependent heterogeneity of tumor endothelial cells (TECs) on tumorigenesis is unclear. Here, we isolated pure TECs from human colorectal carcinomas (CRCs) that exhibited TMEs with either improved (Th1-TME CRCs) or worse clinical prognosis (control-TME CRCs). Transcriptome analyses identified markedly different gene clusters that reflected the tumorigenic and angiogenic activities of the respective TMEs. The gene encoding the matricellular protein SPARCL1 was most strongly upregulated in Th1-TME TECs. It was also highly expressed in ECs in healthy colon tissues and Th1-TME CRCs but low in control-TME CRCs. In vitro, SPARCL1 expression was induced in confluent, quiescent ECs and functionally contributed to EC quiescence by inhibiting proliferation, migration, and sprouting, whereas siRNA-mediated knockdown increased sprouting. In human CRC tissues and mouse models, vessels with SPARCL1 expression were larger and more densely covered by mural cells. SPARCL1 secretion from quiescent ECs inhibited mural cell migration, which likely led to stabilized mural cell coverage of mature vessels. Together, these findings demonstrate TME-dependent intertumoral TEC heterogeneity in CRC. They further indicate that TEC heterogeneity is regulated by SPARCL1, which promotes the cell quiescence and vessel homeostasis contributing to the favorable prognoses associated with Th1-TME CRCs.
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http://dx.doi.org/10.1172/JCI78260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5096916PMC
November 2016

Pathophysiological role of guanylate-binding proteins in gastrointestinal diseases.

World J Gastroenterol 2016 Jul;22(28):6434-43

Nathalie Britzen-Laurent, Elisabeth Naschberger, Michael Stürzl, Division of Molecular and Experimental Surgery, Department of Surgery, University Medical Center Erlangen, Translational Research Center, Friedrich-Alexander University of Erlangen-Nuremberg, 91054 Erlangen, Germany.

Guanylate-binding proteins (GBPs) are interferon-stimulated factors involved in the defense against cellular pathogens and inflammation. These proteins, particularly GBP-1, the most prominent member of the family, have been established as reliable markers of interferon-γ-activated cells in various diseases, including colorectal carcinoma (CRC) and inflammatory bowel diseases (IBDs). In CRC, GBP-1 expression is associated with a Th1-dominated angiostatic micromilieu and is correlated with a better outcome. Inhibition of tumor growth by GBP-1 is the result of its strong anti-angiogenic activity as well as its direct anti-tumorigenic effect on tumor cells. In IBD, GBP-1 mediates the anti-proliferative effects of interferon-γ on intestinal epithelial cells. In addition, it plays a protective role on the mucosa by preventing cell apoptosis, by inhibiting angiogenesis and by regulating the T-cell receptor signaling. These functions rely to a large extent on the ability of GBP-1 to interact with and remodel the actin cytoskeleton.
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http://dx.doi.org/10.3748/wjg.v22.i28.6434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4968125PMC
July 2016

Robotic liver surgery for minor hepatic resections: a comparison with laparoscopic and open standard procedures.

Langenbecks Arch Surg 2016 Aug 20;401(5):707-14. Epub 2016 May 20.

Department of Surgery, Liver Center, University Hospital Erlangen, Krankenhausstrasse 12, 91054, Erlangen, Germany.

Background: Minimally invasive liver surgery is increasing worldwide. The benefit of the robot in this scenario is currently controversially discussed. We compared our robotic cases vs. laparoscopic and open minor hepatic resections and share the experience.

Material And Methods: From 2011 to 2015, ten patients underwent robotic and 19 patients underwent laparoscopic minor liver resections in the Department of Surgery, University Hospital Erlangen. These patients were compared to a case-matched control group of 53 patients. The perioperative prospectively collected data were analyzed retrospectively.

Results: Blood loss was significantly decreased in the robotic (306 ml) and laparoscopic (356 ml) vs. the open (903 ml) surgery group (p = 0.001). Mean tumor size was 4.1-4.8 cm in all groups (p = 0.571). Negative surgical margins were present in 94 % of the open and 100 % of the laparoscopic and robotic group (p = 0.882). Time for surgery was enlarged for robotic (321 min) vs. laparoscopic (242 min) and open (186 min) surgery (p = 0.001). Postoperative hospitalization was decreased after robotic (7 days) and laparoscopic (8 days) vs. open (10 days) surgery (p = 0.004). Total morbidity was 17 % for open, 16 % for laparoscopic, and 1 % for robotic cases (p = 0.345). Postoperative pain medication and elevation of liver enzymes were remarkably lower after minimally invasive vs. open procedures.

Conclusion: Minimally invasive liver surgery can be performed safely for minor hepatic resections and should be considered whenever possible. Minor liver resections can be performed by standard laparoscopy equivalent to robotic procedures. Nevertheless, the robot adds a technical upgrade which may have benefits for challenging cases and major liver surgery.
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http://dx.doi.org/10.1007/s00423-016-1440-1DOI Listing
August 2016

Prognostic and diagnostic value of procalcitonin in the post-transplant setting after liver transplantation.

Arch Med Sci 2016 Apr 12;12(2):372-9. Epub 2016 Apr 12.

Department of Surgery, University Hospital Erlangen, Erlangen, Germany.

Introduction: The aim of the study was to assess the diagnostic accuracy of procalcitonin (PCT) as a marker for complications and as a prognostic factor for mortality after liver transplantation.

Material And Methods: Liver transplant patients between January 2007 and April 2011 were prospectively included in the study. Procalcitonin serum concentration was recorded before, 6 h after reperfusion and then daily. Postoperative clinical course was prospectively analyzed from admission to discharge. Main surgical data such as operating procedure, type of reperfusion, operating and ischemic times, high urgency (HU) status and MELD score at the time of transplantation were also recorded.

Results: Sixteen patients with initial PCT > 5 ng/ml suffered ≥ 1 complication (p = 0.03). However, there was no association between the level of the 1(st) peak PCT and the further postoperative course or the occurrence of complications. Patients in whom a 2(nd) PCT peak occurred had a significantly higher risk for a complicated course, for a complicated sepsis course and for mortality (p < 0.0001). Warm ischemic time over 58 min, operating time over 389 min and HU status were significant independent factors for a complicated postoperative course (p < 0.001, p < 0.001 and p = 0.03 respectively).

Conclusions: Based on our results, we believe that PCT course and the occurrence of a 2(nd) peak seem to possess important diagnostic and prognostic power in the post-transplant setting after liver transplantation.
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http://dx.doi.org/10.5114/aoms.2016.59264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848368PMC
April 2016

The Influence of Liver Resection on Intrahepatic Tumor Growth.

J Vis Exp 2016 Apr 9(110):e53946. Epub 2016 Apr 9.

Department of Surgery, University Hospital Erlangen.

The high incidence of tumor recurrence after resection of metastatic liver lesions remains an unsolved problem. Small tumor cell deposits, which are not detectable by routine clinical imaging, may be stimulated by hepatic regeneration factors after liver resection. It is not entirely clear, however, which factors are crucial for tumor recurrence. The presented mouse model may be useful to explore the mechanisms that play a role in the development of recurrent malignant lesions after liver resection. The model combines the easy-to-perform and reproducible techniques of defined amounts of liver tissue removal and tumor induction (by injection) in mice. The animals were treated with either a single laparotomy, a 30% liver resection, or a 70% liver resection. All animals subsequently received a tumor cell injection into the remaining liver tissue. After two weeks of observation, the livers and tumors were evaluated for size and weight and examined by immunohistochemistry. After a 70% liver resection, the tumor volume and weight were significantly increased compared to a laparotomy alone (p <0.05). In addition, immunohistochemistry (Ki67) showed an increased tumor proliferation rate in the resection group (p <0.05). These findings demonstrate the influence of hepatic regeneration mechanisms on intrahepatic tumor growth. Combined with methods like histological workup or RNA analysis, the described mouse model could serve as foundation for a close examination of different factors involved in tumor growth and metastatic disease recurrence within the liver. A considerable number of variables like the length of postoperative observation, the cell line used for injection or the timing of injection and liver resection offer multiple angles when exploring a specific question in the context of post-hepatectomy metastases. The limitations of this procedure are the authorization to perform the procedure on animals, access to an appropriate animal testing facility and acquisition of certain equipment.
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http://dx.doi.org/10.3791/53946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941904PMC
April 2016

IRAK-M Expression in Tumor Cells Supports Colorectal Cancer Progression through Reduction of Antimicrobial Defense and Stabilization of STAT3.

Cancer Cell 2016 05 14;29(5):684-696. Epub 2016 Apr 14.

Department of Surgery, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany; Regensburg Center for Interventional Immunology, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany. Electronic address:

Colorectal cancer (CRC) is associated with loss of epithelial barrier integrity, which facilitates the interaction of the immunological microenvironment with the luminal microbiome, eliciting tumor-supportive inflammation. An important regulator of intestinal inflammatory responses is IRAK-M, a negative regulator of TLR signaling. Here we investigate the compartment-specific impact of IRAK-M on colorectal carcinogenesis using a mouse model. We demonstrate that IRAK-M is expressed in tumor cells due to combined TLR and Wnt activation. Tumor cell-intrinsic IRAK-M is responsible for regulation of microbial colonization of tumors and STAT3 protein stability in tumor cells, leading to tumor cell proliferation. IRAK-M expression in human CRCs is associated with poor prognosis. These results suggest that IRAK-M may be a potential therapeutic target for CRC treatment.
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http://dx.doi.org/10.1016/j.ccell.2016.03.014DOI Listing
May 2016

Repeated cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with recurrent peritoneal carcinomatosis.

World J Surg Oncol 2016 Feb 24;14(1):42. Epub 2016 Feb 24.

Department of Surgery, University Hospital Erlangen, Krankenhausstrasse 12, 91054, Erlangen, Germany.

Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has become the treatment of choice for resectable peritoneal carcinomatosis (PC) and improved the survival of these patients. The situation changes if PC recurs and repeated CRS with HIPEC is considered. The patient selection and outcome of the repeated approach has not been well described. We analyzed our cohort and share the experiences.

Methods: Ninety-three CRS/HIPEC procedures, performed in 85 patients during the period 2001-2013, were examined in a retrospective analysis. Type of primary, ECOG status, peritoneal cancer index (PCI), completeness of cytoreduction (CC), duration of hospitalization, postoperative morbidity, mortality, and disease-free/overall survival were reviewed.

Results: Six patients (7%) underwent a second CRS/HIPEC (median interval between the two procedures: 26 months, range 8-61) including two patients with mesotheliomas, one patient with ovarian adenocarcinoma, one patient with leiomyosarcoma of uterus, one patient with colon adenocarcinoma, and one patient with appendiceal adenocarcinoma. The last two patients underwent a third CRS/HIPEC, 25 and 36 months, after the second procedure. The median PCI was 14 (range, 4-26) during the first and 20 (range, 7-39) during the second CRS/HIPEC of these patients. Completeness of cytoreduction score of 0 (CC-0) was achieved in all first procedures and in 67% of second procedures (CC-0; n=4 and CC-1; n=2). A CC-0 score was possible in both of the third procedures. The mean operating time was 444 min (range, 198-642) and 427 min (range, 239-617) during the first and the second procedure. Median intensive care unit (ICU) was 2 days, and hospital stay after second CRS/HIPEC was 17 days (range, 7-50). The 30-day morbidity after repeated CRS/HIPEC was 33% (16% for grade III-IV complications), and there was no 30-day mortality neither after the second nor after the third CRS/HIPEC. Median disease-free interval between first CRS/HIPEC and peritoneal recurrence was 17 months (range, 8-30). Median disease-free survival of 18 months (range, 4-33) was achieved after the second CRS/HIPEC. After a median follow-up of 74 months (range, 39-151), all patients are alive with disease (n=5) or disease free (n=1) under chemotherapy.

Conclusions: In experienced centers, repeated CRS/HIPEC can be performed with safety. Patient selection and correct timing is of particular importance in achieving control of the disease. Repeated CRS/HIPEC should be considered as treatment option for selected patients with recurrent PC.
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http://dx.doi.org/10.1186/s12957-016-0804-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4765140PMC
February 2016

Identification of Predictive Markers for Response to Neoadjuvant Chemoradiation in Rectal Carcinomas by Proteomic Isotope Coded Protein Label (ICPL) Analysis.

Int J Mol Sci 2016 Feb 4;17(2):209. Epub 2016 Feb 4.

Max-Planck-Institute of Biochemistry, Martinsried 82152, Germany.

Neoadjuvant chemoradiation (nCRT) is an established procedure in stage union internationale contre le cancer (UICC) II/III rectal carcinomas. Around 53% of the tumours present with good tumor regression after nCRT, and 8%-15% are complete responders. Reliable selection markers would allow the identification of poor or non-responders prior to therapy. Tumor biopsies were harvested from 20 patients with rectal carcinomas, and stored in liquid nitrogen prior to therapy after obtaining patients' informed consent (Erlangen-No.3784). Patients received standardized nCRT with 5-Fluoruracil (nCRT I) or 5-Fluoruracil ± Oxaliplatin (nCRT II) according to the CAO/ARO/AIO-04 protocol. After surgery, regression grading (Dworak) of the tumors was performed during histopathological examination of the specimens. Tumors were classified as poor (Dworak 1 + 2) or good (Dworak 3 + 4) responders. Laser capture microdissection (LCM) for tumor enrichment was performed on preoperative biopsies. Differences in expressed proteins between poor and good responders to nCRT I and II were identified by proteomic analysis (Isotope Coded Protein Label, ICPL™) and selected markers were validated by immunohistochemistry. Tumors of 10 patients were classified as histopathologically poor (Dworak 1 or 2) and the other 10 tumor samples as histopathologically good (Dworak 3 or 4) responders to nCRT after surgery. Sufficient material in good quality was harvested for ICPL analysis by LCM from all biopsies. We identified 140 differentially regulated proteins regarding the selection criteria and the response to nCRT. Fourteen of these proteins were synchronously up-regulated at least 1.5-fold after nCRT I or nCRT II (e.g., FLNB, TKT, PKM2, SERINB1, IGHG2). Thirty-five proteins showed a complete reciprocal regulation (up or down) after nCRT I or nCRT II and the rest was regulated either according to nCRT I or II. The protein expression of regulated proteins such as PLEC1, TKT, HADHA and TAGLN was validated successfully by immunohistochemistry. ICPL is a valid method to identify differentially expressed proteins in rectal carcinoma tissue between poor vs. good responders to nCRT. The identified protein markers may act as selection criteria for nCRT in the future, but our preliminary findings must be reproduced and validated in a prospective cohort.
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http://dx.doi.org/10.3390/ijms17020209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783941PMC
February 2016

MiRNA-21 Expression Decreases from Primary Tumors to Liver Metastases in Colorectal Carcinoma.

PLoS One 2016 4;11(2):e0148580. Epub 2016 Feb 4.

Clinic of Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, Krankenhausstr. 12, 91054, Erlangen, Germany.

Objective: Metastasis is the major cause of death in colorectal cancer patients. Expression of certain miRNAs in the primary tumors has been shown to be associated with progression of colorectal cancer and the initiation of metastasis. In this study, we compared miRNA expression in primary colorectal cancer and corresponding liver metastases in order to get an idea of the oncogenic importance of the miRNAs in established metastases.

Methods: We analyzed the expression of miRNA-21, miRNA-31 and miRNA-373 in corresponding formalin-fixed paraffin-embedded (FFPE) tissue samples of primary colorectal cancer, liver metastasis and healthy tissues of 29 patients by quantitative real-time PCR.

Results: All three miRNAs were significantly up-regulated in the primary tumor tissues as compared to healthy colon mucosa of the respective patients (p < 0.01). MiRNA-21 and miRNA-31 were also higher expressed in liver metastases as compared to healthy liver tissues (p < 0.01). No significant difference of expression of miRNA-31 and miRNA-373 was observed between primary tumors and metastases. Of note, miRNA-21 expression was significantly reduced in liver metastases as compared to the primary colorectal tumors (p < 0.01).

Conclusion: In the context of previous studies demonstrating increased miRNA-21 expression in metastatic primary tumors, our findings raise the question whether miRNA-21 might be involved in the initiation but not in the perpetuation and growth of metastases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0148580PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741388PMC
July 2016

Robotic Pancreatic Resections: Feasibility and Advantages.

Authors:
Roland S Croner

Indian J Surg 2015 Oct 13;77(5):433-5. Epub 2015 Nov 13.

Department of Surgery, University Hospital Erlangen, Krankenhausstrasse 12, 91054 Erlangen, Germany.

The robot is an innovative tool to perform complex pancreatic resections. It upgrades conventional laparoscopy by adding specific ergonomic technical details (e.g., EndoWrist). Robotic complex pancreatic operations such as pancreaticoduodenectomy can be carried out safe with equal oncological results, morbidity, and mortality compared to open procedures. The patients benefit from less blood loss, decreased hospitalization, and all other benefits of minimally invasive surgery. Nevertheless, the robot has some limitations like missing haptic feedback and the high costs. It has to find its indications beneath conventional laparoscopic procedures, which is currently extensively discussed. But the available technology is certainly convincing, and a further improvement can be expected which will increase its widespread in the future.
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http://dx.doi.org/10.1007/s12262-015-1391-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4689699PMC
October 2015

Pioneering Robotic Liver Surgery in Germany: First Experiences with Liver Malignancies.

Front Surg 2015 20;2:18. Epub 2015 May 20.

Department of Surgery and Liver Center, University Hospital Erlangen , Erlangen , Germany.

Background: Minimally invasive liver surgery is growing worldwide with obvious benefits for the treated patients. These procedures maybe improved by robotic techniques, which add several innovative features. In Germany, we were the first surgical department implementing robotic assisted minimally invasive liver resections.

Material And Methods: Between June 2013 and March 2015, we performed robotic based minimally invasive liver resections in nine patients with malignant liver disease. Five off these patients suffered from primary and four from secondary liver malignancies. We retrospectively analyzed the perioperative variables of these patients and the oncological follow up.

Results: Mean age of the patients was 63 years (range 45-71). One patient suffered from intrahepatic cholangiocellular, four from hepatocellular carcinoma, and four patients from colorectal liver metastases. In six patients, left lateral liver resection, in two cases single segment resection, and in one case minimally invasive guided liver ablation were performed. Five patients underwent previous abdominal surgery. Mean operation time was 312 min (range 115-458 min). Mean weight of the liver specimens was 182 g (range 62-260 g) and mean estimated blood loss was 251 ml (range 10-650 ml). The mean tumor size was 4.4 cm (range 3.5-5.5 cm). In all cases, R0 status was confirmed with a mean margin of 0.6 cm (range 0.1-1.5 cm). One patient developed small bowel fistula on postoperative day 5, which could be treated conservatively. No patient died. Mean hospital stay of the patients was 6 days (range 3-10 days). During a mean follow up of 12 months (range 1-21 months), two patients developed tumor recurrence.

Conclusion: Robotic-based liver surgery is feasible in patients with primary and secondary liver malignancies. To achieve perioperative parameters comparable to open settings, the learning curve must be passed. Minor liver resections are good candidates to start this technique. But the huge benefits of robotic-based liver resections should be expected in extended procedures beyond minor liver resections with the currently available technology.
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http://dx.doi.org/10.3389/fsurg.2015.00018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4440394PMC
June 2015

Management of liver metastases of gastrointestinal stromal tumors (GIST).

Ann Hepatol 2015 Jul-Aug;14(4):531-9

Department of Surgery Germany.

Introduction: Liver metastases (LM) are crucial prognostic manifestation of gastrointestinal stromal tumors (GIST). With the advent of tyrosine kinase inhibitors (TKI), management of metastatic GIST has radically changed. Long clinical follow-up provides an increased proportion of GIST patients with LM who are candidates for potentially curative therapy.

Material And Methods: Patients who underwent treatment for liver metastases of GIST between 2000-2009 in our department were included in the study. Mean follow-up was 84 months (range 40-145) months. In retrospective analysis we investigated clinical, macro-/microscopic and immunohistochemical criteria, surgical, interventional and TKI therapy as well.

Results: In 87 GIST-patients we identified 25 (29%) patients with metastatic disease. Of these, 12 patients (14%) suffered from LM with a mean age of 60.5 (range, 35-75) years. Primary GIST were located at stomach (n = 4, 33%) or small intestine (n = 8, 67%); all of them expressed CD117 and/or CD34. LM were multiple (83%), distributed in both lobes (67%). They were detected synchronously with primary tumor in 33% and metachronously in 77%. All patients with liver involvement were considered to treatment with TKI. LM were resected (R0) in 4 patients (33%). In recurrent (2/4) and TKI resistant cases, interventional treatment (radiofrequency ablation) and TKI escalation were carried out. During a median follow-up of 84 months (range 30-152), 2 patients died (16.5%) for progressive disease and one patient for other reasons. Nine patients (75%) were alive.

Conclusion: Treatment of LM from GIST needs a multimodal approach. TKI-therapy is required at any case. In case of respectability, surgery must be carried out. In unresectable cases or recurrent/progressive disease, interventional treatment or TKI escalation should be considered. Therefore, these patients need to be treated in experienced centres, where multimodal approaches are established.
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February 2016
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