153 results on '"Stephan, Kersting"'
Search Results
2. Cold Atmospheric Plasma Is a Promising Alternative Treatment Option in Case of Split Skin Graft Failure
- Author
-
Aydar Khabipov, Andre Schreiber, Stephan Kersting, Richard Hummel, Johannes Höhn, Lars-Ivo Partecke, Sander Bekeschus, Anne Glitsch, and Wolfram Keßler
- Subjects
Surgery ,RD1-811 - Abstract
Cold atmospheric plasma (CAP) has shown promising potential in promoting wound healing. This case report presents the successful application of CAP in a 42-year-old female patient with extensive wound healing disorders and superinfections following the excision of an abscess in the left thoracic region. After several failed split skin graft attempts, the implementation of CAP led to significant improvements in wound healing. This report highlights the wound healing-promoting effects of CAP and discusses its potential mechanisms of action.
- Published
- 2024
- Full Text
- View/download PDF
3. Continuous or interrupted suture technique for hepaticojejunostomy during pancreatoduodenectomy (HEKTIK trial): study protocol of a randomized controlled multicenter trial
- Author
-
Maximilian Brunner, Henriette Golcher, Christian Krautz, Stephan Kersting, Georg F. Weber, and Robert Grützmann
- Subjects
Hepaticojejunostomy ,Suture technique ,Pancreatoduodenectomy ,Continuous suture technique ,Interrupted suture technique ,Medicine (General) ,R5-920 - Abstract
Abstract Background Hepaticojejunostomy is commonly performed in hepato-bilio-pancreatic surgery, particularly during pancreaticoduodenectomy. The purpose of this study is to evaluate the safety and efficiency of two commonly applied suture techniques (the interrupted versus the continuous suture technique) in patients undergoing a hepaticojejunostomy during pancreatoduodenectomy. Methods The HEKTIK trial is a multicenter, randomized controlled, patient-blinded surgical explorative trial with two parallel study groups. An adaptive sample size design was chosen: First, 100 patients scheduled for surgery including a hepaticojejunostomy will be randomized 1:1 either to the interrupted suture technique or the continuous suture technique after informed consent. Based on this data, needed sample size will be adjusted. The primary endpoint will be the occurrence of anastomotic leakage of hepaticojejunostomy, defined as bilirubin concentration in the drain fluid at least 3 times the serum bilirubin concentration on or after postoperative day 3 or as the need for radiologic or operative intervention resulting from biliary collections or bile peritonitis (according to the definition of ISGLS). Further perioperative parameters like other morbidities as well as duration and costs of the hepaticojejunostomy will be analyzed as secondary outcomes. Discussion Until now there are no randomized controlled comparative data of these two suture techniques for hepaticojejunostomy. The HEKTIK trial will investigate the yet unanswered question of whether the interrupted suture or the continuous suture technique has advantages performing a hepaticojejunostomy during pancreatoduodenectomy. Trial registration German Clinical Trials Register DRKS00024395 . Registered on 01 February 2021.
- Published
- 2022
- Full Text
- View/download PDF
4. CCR4 Blockade Diminishes Intratumoral Macrophage Recruitment and Augments Survival of Syngeneic Pancreatic Cancer-Bearing Mice
- Author
-
Aydar Khabipov, Dung Nguyen Trung, Julia van der Linde, Lea Miebach, Maik Lenz, Felix Erne, Wolfram von Bernstorff, Tobias Schulze, Stephan Kersting, Sander Bekeschus, and Lars Ivo Partecke
- Subjects
CCL17 ,CCL22 ,M2 macrophages ,migration ,TAMs ,tumor-associated macrophages ,Biology (General) ,QH301-705.5 - Abstract
Pancreatic cancer is known for its tumor microenvironment (TME), which is rich in stromal and immune cells supporting cancer growth and therapy resistance. In particular, tumor-associated macrophages (TAMs) are known for their angiogenesis- and metastasis-promoting properties, which lead to the failure of conventional therapies for pancreatic cancer. Hence, treatment options targeting TAMs are needed. The C-C chemokine receptor type 4 (CCR4) is critical for immune cell recruitment into the TME, and in this paper we explore the effects of its genetic or immunotherapeutic blockade in pancreatic-cancer-bearing mice. Murine PDA6606 pancreatic cancer cells and murine peritoneal macrophages were used for in vitro migration assays. In vivo, a syngeneic, orthotropic pancreatic cancer model was established. Tumor growth and survival were monitored under prophylactic and therapeutic application of a CCR4 antagonist (AF-399/420/18025) in wildtype (CCR4wt) and CCR4-knockout (CCR4−/−) mice. Immune infiltration was monitored in tumor tissue sections and via flow cytometry of lysed tumors. PDA6606 cells induced less migration in CCR4−/− than in CCR4wt macrophages in vitro. Pancreatic TAM infiltration was higher, and survival was reduced in CCR4wt mice compared to CCR4−/− mice. Antagonizing CCR4 in wildtype mice revealed similar results as in CCR4−/− mice without antagonization. Prophylactic CCR4 antagonist application in wildtype mice was more efficient than therapeutic antagonization. CCR4 seems to be critically involved in TAM generation and tumor progression in pancreatic cancer. CCR4 blockade may help prolong the relapse-free period after curative surgery in pancreatic cancer and improve prognosis.
- Published
- 2023
- Full Text
- View/download PDF
5. In-hospital mortality and failure to rescue following hepatobiliary surgery in Germany - a nationwide analysis
- Author
-
Christian Krautz, Christine Gall, Olaf Gefeller, Ulrike Nimptsch, Thomas Mansky, Maximilian Brunner, Georg F. Weber, Robert Grützmann, and Stephan Kersting
- Subjects
Surgery ,RD1-811 - Abstract
Abstract Background Recent observational studies on volume-outcome associations in hepatobiliary surgery were not designed to account for the varying extent of hepatobiliary resections and the consequential risk of perioperative morbidity and mortality. Therefore, this study aimed to determine the risk-adjusted in-hospital mortality for minor and major hepatobiliary resections at the national level in Germany and to examine the effect of hospital volume on in-hospital mortality, and failure to rescue. Methods All inpatient cases of hepatobiliary surgery (n = 31,114) in Germany from 2009 to 2015 were studied using national hospital discharge data. After ranking hospitals according to increasing hospital volumes, five volume categories were established based on all hepatobiliary resections. The association between hospital volume and in-hospital mortality following minor and major hepatobiliary resections was evaluated by multivariable regression methods. Results Minor hepatobiliary resections were associated with an overall mortality rate of 3.9% and showed no significant volume-outcome associations. In contrast, overall mortality rate of major hepatobiliary resections was 10.3%. In this cohort, risk-adjusted in-hospital mortality following major resections varied widely across hospital volume categories, from 11.4% (95% CI 10.4–12.5) in very low volume hospitals to 7.4% (95% CI 6.6–8.2) in very high volume hospitals (risk-adjusted OR 0.59, 95% CI 0.41–0.54). Moreover, rates of failure to rescue decreased from 29.38% (95% CI 26.7–32.2) in very low volume hospitals to 21.38% (95% CI 19.2–23.8) in very high volume hospitals. Conclusions In Germany, patients who are undergoing major hepatobiliary resections have improved outcomes, if they are admitted to higher volume hospitals. However, such associations are not evident following minor hepatobiliary resections. Following major hepatobiliary resections, 70–80% of the excess mortality in very low volume hospitals was estimated to be attributable to failure to rescue.
- Published
- 2020
- Full Text
- View/download PDF
6. Disseminated Intravascular Coagulation (DIC): Old player creates new perspectives on the polymicrobial sepsis model of CASP.
- Author
-
Julia van der Linde, Stephan Diedrich, Thorben Klee, Claus-Dieter Heidecke, Stephan Kersting, and Wolfram Keßler
- Subjects
Medicine ,Science - Abstract
BackgroundDisseminated Intravascular Coagulation (DIC) is a life-threatening complication of sepsis. In surgical ICUs, DIC is frequently caused by abdominal sepsis, and the disarranged coagulation and complications often lead to death. The severity of sepsis is associated with a higher DIC score according to the parameters proposed by the International Society of Hemostasis and Thrombosis (ISTH) in 2001: platelet count, bleeding time (Quick), D-dimer, and fibrinogen. One problem in studying DIC is finding an adequate animal model that reflects the clinical situation of polymicrobial overwhelming infection.Aims and methodsWe investigated whether a well-established polymicrobial sepsis model of colon ascendens stent peritonitis (CASP) is suited to investigate the complexity of DIC. For this purpose, CASP-operated mice were examined 20 h after the operation with regard to coagulation parameters using cell counts, bleeding times, rotational thromboelastometry (ROTEM), ELISAs for D-dimer and fibrinogen, and platelet accumulation in affected organs via immunohistochemistry to see if the mice develop a coagulation disorder that meets the definition of DIC proposed by the ISTH 2001 consensus conference.ResultsHerein, we showed that the CASP model is an all-encompassing animal model to analyze the complexity of systemic DIC in murine abdominal sepsis. There is highly reproducible thrombocytopenia, a significant prolongation of the bleeding time, and a loss of fibrinogen in plasma. We also observed microvascular thrombosis due to platelet accumulation in the microcirculation of the liver.ConclusionThe CASP model seems superior to other artificial models, e.g., injecting substances, for inducing DIC. CASP is one of the best true-to-life models for analyzing the complexity of disseminated intravascular coagulation in polymicrobial sepsis.
- Published
- 2022
- Full Text
- View/download PDF
7. NCR, an Inflammation and Nutrition Related Blood-Based Marker in Colon Cancer Patients: A New Promising Biomarker to Predict Outcome
- Author
-
Melanie Langheinrich, Alexander Reinhard Siebenhüner, Justus Baecker, Maximilian Miragall, Felix Wiesmüller, Vera Schellerer, Susanne Merkel, Maximilian Brunner, Christian Krautz, Klaus Weber, Robert Grützmann, and Stephan Kersting
- Subjects
colorectal cancer ,colon cancer ,biomarker ,tumor marker ,inflammation ,nutrition ,Medicine (General) ,R5-920 - Abstract
Background: Colorectal carcinoma (CRC) is a heterogeneous disease, and differences in outcomes have been reported among patients diagnosed with the same disease stage. Prognostic and predictive biomarkers provide information for patient risk stratification and guide treatment selection. Although numerous studies have analyzed the effects of systemic inflammatory factors on CRC outcomes, clinical significance remains to be elucidated. In particular, the treatment strategy of colon cancer patients is different from that of rectal cancer due to outcome and recurrence differences. The identification of patients with a poor prognosis who might benefit from intensive treatment approaches is clinically necessary. Methods: This study aimed to evaluate the value of different blood-based markers and assess the significance of our newly developed inflammatory-nutrition-related biomarker (NCR = BMI × albumin/CRP) in patients with colon cancer. A two-stage design was used with 212 patients with colon cancer (CC) in the discovery cohort (n = 159) and in an external validation cohort (n = 53). Results: A lower preoperative NCR level was significantly correlated with a worse prognosis, sidedness, undifferentiated histology, nodal involvement, and advanced UICC stage. We compared the NCR with other established prognostic indices and showed that the NCR is a more reliable indicator of a poor prognosis for patients with CC. Patients with low NCR levels experienced a significantly shorter Overall Survival (OS) than patients with high levels. Multivariate analysis confirmed preoperative NCR levels as an independent predictor for overall survival with a hazard ratio of 3.3 (95% confidence interval 1.628–6.709, p < 0.001). Finally, we confirmed the predictive value of the NCR in an independent validation cohort and confirmed NCR as an independent prognostic factor for OS. Conclusion: Taken together, we discovered a new prognostic index (NCR) based on BMI, albumin, and CRP levels as an independent prognostic predictor of OS in patients with colon cancer. In all UICC stages, our newly developed NCR marker is able to distinguish patients with better and worse prognoses. We, therefore, propose that NCR may serve as a supplement to the TNM staging system to optimize the risk stratification in CC patients towards personalized oncology. In particular, NCR can be used in clinical trials to stratify patients with UICC II and III tumors and help better select patients who might benefit from adjuvant treatment.
- Published
- 2022
- Full Text
- View/download PDF
8. MiR-132 controls pancreatic beta cell proliferation and survival through Pten/Akt/Foxo3 signaling
- Author
-
Hassan Mziaut, Georg Henniger, Katharina Ganss, Sebastian Hempel, Steffen Wolk, Johanna McChord, Kamal Chowdhury, Philippe Ravassard, Klaus-Peter Knoch, Christian Krautz, Jürgen Weitz, Robert Grützmann, Christian Pilarsky, Michele Solimena, and Stephan Kersting
- Subjects
Internal medicine ,RC31-1245 - Abstract
Objective: MicroRNAs (miRNAs) play an integral role in maintaining beta cell function and identity. Deciphering their targets and precise role, however, remains challenging. In this study, we aimed to identify miRNAs and their downstream targets involved in the regeneration of islet beta cells following partial pancreatectomy in mice. Methods: RNA from laser capture microdissected (LCM) islets of partially pancreatectomized and sham-operated mice were profiled with microarrays to identify putative miRNAs implicated in beta cell regeneration. Altered expression of the selected miRNAs, including miR-132, was verified by RT-PCR. Potential targets of miR-132 were selected through bioinformatic data mining. Predicted miR-132 targets were validated for their changed RNA, protein expression levels, and signaling upon miR-132 knockdown and/or overexpression in mouse MIN6 and human EndoC-βH1 insulinoma cells. The ability of miR-132 to foster beta cell proliferation in vivo was further assessed in pancreatectomized miR-132−/− and control mice. Results: Partial pancreatectomy significantly increased the number of BrdU+/insulin+ islet cells. Microarray profiling revealed that 14 miRNAs, including miR-132 and -141, were significantly upregulated in the LCM islets of the partially pancreatectomized mice compared to the LCM islets of the control mice. In the same comparison, miR-760 was the only downregulated miRNA. The changed expression of these miRNAs in the islets of the partially pancreatectomized mice was confirmed by RT-PCR only in the case of miR-132 and -141. Based on previous knowledge of its function, we focused our attention on miR-132. Downregulation of miR-132 reduced the proliferation of MIN6 cells while enhancing the levels of pro-apoptotic cleaved caspase-9. The opposite was observed in miR-132 overexpressing MIN6 cells. Microarray profiling, RT-PCR, and immunoblotting of the latter cells demonstrated their downregulated expression of Pten with concomitant increased levels of pro-proliferative factors phospho-Akt and phospho-Creb and inactivation of pro-apoptotic Foxo3a via its phosphorylation. Downregulation of Pten was further confirmed in the LCM islets of pancreatectomized mice compared to the sham-operated mice. Moreover, overexpression of miR-132 correlated with increased proliferation of EndoC-βH1 cells. The regeneration of beta cells following partial pancreatectomy was lower in the miR-132/212−/− mice than the control littermates. Conclusions: This study provides compelling evidence about the critical role of miR-132 for the regeneration of mouse islet beta cells through the downregulation of its target Pten. Hence, the miR-132/Pten/Akt/Foxo3 signaling pathway may represent a suitable target to enhance beta cell mass. Keywords: miR-132, β cell regeneration, Apoptosis, Pten/Akt/Foxo3a, Pancreatectomy
- Published
- 2020
- Full Text
- View/download PDF
9. Effects of regional anesthesia techniques on local anesthetic plasma levels and complications in carotid surgery: a randomized controlled pilot trial
- Author
-
Thomas Rössel, Christopher Uhlig, Jörg Pietsch, Stefan Ludwig, Thea Koch, Torsten Richter, Peter Markus Spieth, and Stephan Kersting
- Subjects
Carotid endarterectomy ,Cervical plexus block ,Plasma concentration ,Regional anesthesia ,Local anesthetic ,Ropivacaine ,Anesthesiology ,RD78.3-87.3 - Abstract
Abstract Background The ultrasound guided intermediate cervical plexus block with perivascular infiltration of the internal carotid artery (PVB) is a new technique for regional anesthesia in carotid endarterectomy (CEA). We conducted a pilot study investigating the effects of deep cervical block (DCB), intermediate cervical block alone (ICB) and PVB on perioperative complications in patients undergoing elective CEA. We hypothesized, that the ropivacaine plasma concentration is higher in patients receiving DCB compared to PVB and ICB. Methods In a randomized controlled pilot study thirty patients scheduled for elective CEA were randomly assigned into three groups: DCB receiving 20 mL ropivacaine 0.5% (n = 10), ICB receiving 20 mL ropivacaine 0.5% (n = 10) and PVB receiving 20 mL ropivacaine 0.5% and 10 mL ropivacaine 0,3% (n = 10). As primary outcome, plasma levels of ropivacaine were measured with high performance liquid chromatography before, 5, 10, 20, 60, and 180 min after the injection of ropivacaine. Secondary outcomes were vascular and neurological complications as well as patients’ and surgeons’ satisfaction. All analyses were performed on an intention-to-treat basis. Statistical significance was accepted at p
- Published
- 2019
- Full Text
- View/download PDF
10. Narrowing the therapeutic window?—A case-control study on the influence of the COVID-19 pandemic on the primary UICC stage of NSCLC
- Author
-
Isabella B. Metelmann, Sebastian Kraemer, Matthias Steinert, Stephan Kersting, and Alexandra Busemann
- Subjects
Pulmonary and Respiratory Medicine - Published
- 2023
- Full Text
- View/download PDF
11. Continuous or interrupted suture technique for hepaticojejunostomy? A national survey
- Author
-
Maximilian Brunner, Jessica Stockheim, Christian Krautz, Dimitrios Raptis, Stephan Kersting, Georg F. Weber, and Robert Grützmann
- Subjects
Hepaticojejunostomy ,Pancreatic surgery ,Hepatic surgery ,Surgical technique ,Survey ,Surgery ,RD1-811 - Abstract
Abstract Background Hepaticojejunostomy is commonly used in hepato-bilio-pancreatic surgery and a crucial step in many surgical procedures, including pancreaticoduodenectomy. The most frequently used techniques are the interrupted suture and the continuous suture technique. Currently, there is no data available in regard to the utilization of these techniques. Methods In total, 102 hospitals in Germany were invited between September and November 2017 to participate in this survey. Using a paper-based questionnaire, data were collected on surgical technique and complication rates of hepaticojejunostomies. Results A total of 77 of the 102 addressed hospitals (76%) participated in the survey. On average, each hospital performed 71 hepaticojejunostomies per year - most often in the context of pancreaticoduodenectomy (71%). 24 (31%) hospitals exclusively use an interrupted suture technique, 7 (9%) hospitals solely a continuous suture technique, 3 (4%) hospitals perform a combination of continuous and interrupted suture technique and 43 (56%) hospitals decide on one of both techniques depending on intraoperative findings. According to the participants in this survey, the continuous suture technique is significantly faster than the interrupted suture technique in hepaticojejunostomy (p = 0,015). There were no significant differences in the overall complication rate (p = 0,902) and insufficiency rate (p = 1,000). Conclusions In Germany, there is a heterogeneity in the technique used to create a hepaticojejunostomy. As our survey suggests that the use of continuous suture technique may offer an advantage in time without jeopardizing patient outcomes, the different techniques should be compared in a randomized controlled study.
- Published
- 2018
- Full Text
- View/download PDF
12. Risk Factors for Conversion from Laparoscopic to Open Appendectomy
- Author
-
Brunner, Bruno Leonardo Bancke Laverde, Matthias Maak, Melanie Langheinrich, Stephan Kersting, Axel Denz, Christian Krautz, Georg F. Weber, Robert Grützmann, and Maximilian
- Subjects
acute appendicitis ,laparoscopic approach ,conversion ,morbidity - Abstract
(1) Background: Since its introduction in the 1990s, laparoscopic appendectomy has become established over the years and is today considered the standard therapy for acute appendicitis. In some cases, however, a conversion to the open approach is still necessary. The primary aim of this study was to identify risk factors for the need to convert from the laparoscopic to an open approach during appendectomy for acute appendicitis. (2) Methods: A retrospective analysis of 1220 adult patients who underwent laparoscopic appendectomy for acute appendicitis from 2010 to 2020 at the University Hospital Erlangen was performed. Data, including patient demographics and pre-, intra-, and postoperative findings, were collected and compared between patients with and without conversion. (3) Results: The conversion rate in our cohort was 5.5%. A higher preoperative WBC count and CRP (OR 1.9, p = 0.042, and OR 2.3, p = 0.019, respectively), as well as the presence of intraoperative perforation, necrosis or gangrene, perityphlitic abscess and peritonitis (OR 3.2, p = 0.001; OR 2.3, p = 0.023; OR 2.6, p = 0.006 and OR 2.0, p = 0.025, respectively) were identified as independent risk factors for conversion from the laparoscopic to the open approach. Conversion was again independently associated with higher morbidity (OR 2.2, p = 0.043). (4) Conclusion: The laparoscopic approach is feasible and safe in the majority of patients with acute appendicitis. Only increased inflammatory blood markers could be detected as the preoperative risk factors potentially influencing the choice of surgical approach but only with low specificity and sensitivity. For the decision to convert, intraoperative findings are additionally crucial. However, patients with conversion should receive special attention in the postoperative course, as these have an increased risk of developing complications.
- Published
- 2023
- Full Text
- View/download PDF
13. Omega suture technique for minimally invasive rectal anastomosis – a video vignette
- Author
-
Maximilian Brunner, Klaus Weber, Axel Denz, Melanie Langheinrich, Stephan Kersting, Georg F. Weber, Robert Grützmann, and Christian Krautz
- Subjects
Gastroenterology - Published
- 2023
- Full Text
- View/download PDF
14. Metagenomic Identification of Microbial Signatures Predicting Pancreatic Cancer From a Multinational Study
- Author
-
Naoyoshi Nagata, Suguru Nishijima, Yasushi Kojima, Yuya Hisada, Koh Imbe, Tohru Miyoshi-Akiyama, Wataru Suda, Moto Kimura, Ryo Aoki, Katsunori Sekine, Mitsuru Ohsugi, Kuniko Miki, Tsuyoshi Osawa, Kohjiro Ueki, Shinichi Oka, Masashi Mizokami, Ece Kartal, Thomas S.B. Schmidt, Esther Molina-Montes, Lidia Estudillo, Nuria Malats, Jonel Trebicka, Stephan Kersting, Melanie Langheinrich, Peer Bork, Naomi Uemura, Takao Itoi, and Takashi Kawai
- Subjects
Pancreatic Neoplasms ,Feces ,Hepatology ,Gastroenterology ,Dysbiosis ,Humans ,Metagenome ,Metagenomics ,Prospective Studies - Abstract
To identify gut and oral metagenomic signatures that accurately predict pancreatic ductal carcinoma (PDAC) and to validate these signatures in independent cohorts.We conducted a multinational study and performed shotgun metagenomic analysis of fecal and salivary samples collected from patients with treatment-naïve PDAC and non-PDAC controls in Japan, Spain, and Germany. Taxonomic and functional profiles of the microbiomes were characterized, and metagenomic classifiers to predict PDAC were constructed and validated in external datasets.Comparative metagenomics revealed dysbiosis of both the gut and oral microbiomes and identified 30 gut and 18 oral species significantly associated with PDAC in the Japanese cohort. These microbial signatures achieved high area under the curve values of 0.78 to 0.82. The prediction model trained on the Japanese gut microbiome also had high predictive ability in Spanish and German cohorts, with respective area under the curve values of 0.74 and 0.83, validating its high confidence and versatility for PDAC prediction. Significant enrichments of Streptococcus and Veillonella spp and a depletion of Faecalibacterium prausnitzii were common gut signatures for PDAC in all the 3 cohorts. Prospective follow-up data revealed that patients with certain gut and oral microbial species were at higher risk of PDAC-related mortality. Finally, 58 bacteriophages that could infect microbial species consistently enriched in patients with PDAC across the 3 countries were identified.Metagenomics targeting the gut and oral microbiomes can provide a powerful source of biomarkers for identifying individuals with PDAC and their prognoses. The identification of shared gut microbial signatures for PDAC in Asian and European cohorts indicates the presence of robust and global gut microbial biomarkers.
- Published
- 2022
- Full Text
- View/download PDF
15. The use of single-stapling techniques reduces anastomotic complications in minimal-invasive rectal surgery
- Author
-
Maximilian Brunner, Alaa Zu’bi, Klaus Weber, Axel Denz, Melanie Langheinrich, Stephan Kersting, Georg F. Weber, Robert Grützmann, and Christian Krautz
- Subjects
Anastomosis, Surgical ,Surgical Stapling ,Rectum ,Gastroenterology ,Humans ,Anastomotic Leak - Abstract
Background Leakage of rectal anastomoses is one of the most important and feared complications in colorectal surgery. Apart from patient-specific risk factors, technical aspects may influence the occurrence of anastomotic complications. This study investigated whether using single-stapling techniques (SST) instead of the double-stapling technique (DST) for minimal-invasive rectal anastomosis is associated with a lower rate of anastomotic complications. Methods A retrospective review of 272 patients who received a minimally invasive stapled rectal anastomosis (3–16 cm from the anal verge) at our institution from 2015 to 2020 was performed. In 131 patients, rectal anastomosis was created by SST (SST group), while 141 patients received a rectal anastomosis with crossing stapler lines (DST group). The impact of the anastomotic technique on patient outcomes was determined by uni- and multivariate analyses. Results Overall anastomotic leakage rate was 6%. Patients with SST anastomoses had a lower leakage rate than patients with DST anastomoses (3% vs. 9% in the DST group, p = 0.045). The rate of anastomotic stenosis was lower in the SST group than in the DST group (1% vs. 6%, p = 0.037). Overall morbidity and mortality did not differ between the two groups. Multivariate analysis showed that single-stapling techniques significantly reduce the risk of anastomotic leakage (OR 3.5 [1.0–11.5], p = 0.043). Conclusion The use of SST for rectal anastomosis may help to reduce anastomotic complications. This finding should be confirmed by a randomized controlled trial.
- Published
- 2022
- Full Text
- View/download PDF
16. Colon Cancer Microbiome Landscaping: Differences in Right- and Left-Sided Colon Cancer and a Tumor Microbiome-Ileal Microbiome Association
- Author
-
Barbara Kneis, Stefan Wirtz, Klaus Weber, Axel Denz, Matthias Gittler, Carol Geppert, Maximilian Brunner, Christian Krautz, Alexander Reinhard Siebenhüner, Robert Schierwagen, Olaf Tyc, Abbas Agaimy, Robert Grützmann, Jonel Trebicka, Stephan Kersting, and Melanie Langheinrich
- Subjects
Organic Chemistry ,microbiome ,left-sided colon cancer ,gut microbiome ,General Medicine ,Catalysis ,tumor microbiome ,Computer Science Applications ,Inorganic Chemistry ,colon cancer ,ddc:610 ,Physical and Theoretical Chemistry ,right-sided colon cancer ,Molecular Biology ,Spectroscopy - Abstract
In the current era of precision oncology, it is widely acknowledged that CRC is a heterogeneous disease entity. Tumor location (right- or left-sided colon cancer or rectal cancer) is a crucial factor in determining disease progression as well as prognosis and influences disease management. In the last decade, numerous works have reported that the microbiome is an important element of CRC carcinogenesis, progression and therapy response. Owing to the heterogeneous nature of microbiomes, the findings of these studies were inconsistent. The majority of the studies combined colon cancer (CC) and rectal cancer (RC) samples as CRC for analysis. Furthermore, the small intestine, as the major site for immune surveillance in the gut, is understudied compared to the colon. Thus, the CRC heterogeneity puzzle is far from being solved, and more research is necessary for prospective trials that separately investigate CC and RC. Our prospective study aimed to map the colon cancer landscape using 16S rRNA amplicon sequencing in biopsy samples from the terminal ileum, healthy colon tissue, healthy rectal tissue and tumor tissue as well as in preoperative and postoperative stool samples of 41 patients. While fecal samples provide a good approximation of the average gut microbiome composition, mucosal biopsies allow for detecting subtle variations in local microbial communities. In particular, the small bowel microbiome has remained poorly characterized, mainly because of sampling difficulties. Our analysis revealed the following: (i) right- and left-sided colon cancers harbor distinct and diverse microbiomes, (ii) the tumor microbiome leads to a more consistent cancer-defined microbiome between locations and reveals a tumor microbiome–ileal microbiome association, (iii) the stool only partly reflects the microbiome landscape in patients with CC, and (iv) mechanical bowel preparation and perioperative antibiotics together with surgery result in major changes in the stool microbiome, characterized by a significant increase in the abundance of potentially pathogenic bacteria, such as Enterococcus. Collectively, our results provide new and valuable insights into the complex microbiome landscape in patients with colon cancer.
- Published
- 2023
- Full Text
- View/download PDF
17. Risk factors for postoperative morbidity, prolonged length of stay and hospital readmission after appendectomy for acute appendicitis
- Author
-
Bruno Leonardo Bancke Laverde, Matthias Maak, Melanie Langheinrich, Stephan Kersting, Axel Denz, Christian Krautz, Georg Ferdinand Weber, Robert Grützmann, and Maximilian Brunner
- Subjects
Emergency Medicine ,Orthopedics and Sports Medicine ,Surgery ,Critical Care and Intensive Care Medicine - Abstract
Purpose The aim of the present study was to identify risk factors associated with postoperative morbidity and major morbidity, with a prolonged length of hospital stay and with the need of readmission in patients undergoing appendectomy due to acute appendicitis. Methods We performed a retrospective analysis of 1638 adult patients who underwent emergency appendectomy for preoperatively suspected acute appendicitis from 2010 to 2020 at the University Hospital Erlangen. Data including patient demographics, pre-, intra-, and postoperative findings were collected and compared between different outcome groups (morbidity, major morbidity, prolonged length of postoperative hospital stay (LOS) and readmission) from those patients with verified acute appendicitis (n = 1570). Results Rate of negative appendectomies was 4%. In patients with verified acute appendicitis, morbidity, major morbidity and readmission occurred in 6%, 3% and 2%, respectively. Mean LOS was 3.9 days. Independent risk factors for morbidity were higher age, higher preoperative WBC-count and CRP, lower preoperative hemoglobin, longer time to surgery and longer duration of surgery. As independent risk factors for major morbidity could be identified higher age, higher preoperative CRP, lower preoperative hemoglobin and longer time to surgery. Eight parameters were independent risk factors for a prolonged LOS: higher age, higher preoperative WBC-count and CRP, lower preoperative hemoglobin, need for conversion, longer surgery duration, presence of intraoperative complicated appendicitis and of postoperative morbidity. Presence of malignancy and higher preoperative WBC-count were independent risk factors for readmission. Conclusion Among patients undergoing appendectomy for acute appendicitis, there are relevant risk factors predicting postoperative complications, prolonged hospital stays and readmission. Patients with the presence of the identified risk factors should receive special attention in the postoperative course and may benefit from a more individualized therapy.
- Published
- 2023
- Full Text
- View/download PDF
18. A Possible Distinct Molecular Subtype (Quintuple-Wildtype) of Metastatic Colorectal Cancer in First-Line Anti-EGFR Therapy with Cetuximab Plus FOLFIRI – Palliative Precision Therapy and a Multidisciplinary Treatment Approach: Interim Analysis of the IVOPAK II Trial with Early Results
- Author
-
Jan-Peter Roth, Francesco Vitali, Dagmar Busse, W Schreiner, Susanne Merkel, Robert Stoehr, Arndt Hartmann, Markus Eckstein, Axel Wein, Stephan Kersting, Michael Uder, Peter Anhut, Robert Grützmann, Jürgen Siebler, Nicola Ostermeier, Markus F. Neurath, Kerstin Wolff, and Clemens Neufert
- Subjects
Adult ,Male ,Proto-Oncogene Proteins B-raf ,Oncology ,Neuroblastoma RAS viral oncogene homolog ,Cancer Research ,medicine.medical_specialty ,Bevacizumab ,Class I Phosphatidylinositol 3-Kinases ,Receptor, ErbB-2 ,Colorectal cancer ,Population ,Leucovorin ,Cetuximab ,medicine.disease_cause ,GTP Phosphohydrolases ,Proto-Oncogene Proteins p21(ras) ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Biomarkers, Tumor ,medicine ,Humans ,Precision Medicine ,education ,Aged ,education.field_of_study ,business.industry ,Palliative Care ,Membrane Proteins ,General Medicine ,Middle Aged ,medicine.disease ,Interim analysis ,ErbB Receptors ,FOLFIRI ,Camptothecin ,Female ,Fluorouracil ,KRAS ,Colorectal Neoplasms ,business ,medicine.drug - Abstract
Objective: The study aimed to prospectively evaluate a new molecular biomarker panel (KRAS, NRAS, BRAF, PIK3CA, and ERBB2) for palliative first-line treatment of colorectal cancer (CRC), including a multidisciplinary treatment approach. The rate of secondary metastasis resections was assessed. Patients and Methods: A total of 40 patients with definitively nonresectable metastatic CRC were enrolled from 10 centers before the interim analysis (June 2019) of the IVOPAK II trial (Interdisciplinary Care with Quality Control in Palliative Treatment of Colorectal Cancer). After determination of 5 molecular biomarkers in the tumor (KRAS, exons 2–4; NRAS, exons 2–4; BRAF V600E; PIK3CA; and ERBB2), patients in the IVOPAK II study received FOLFIRI plus cetuximab for all-RAS/quintuple-wildtype disease and FOLFIRI plus bevacizumab in the case of RAS mutations. The current article presents the early description of the clinical outcome of the interim analysis of IVOPAK II comparing the all-RAS/quintuple-wildtype and RAS-mutations populations, including a multidisciplinary-treated case report of a quintuple-wildtype patient. Results: The quintuple-wildtype population treated with FOLFIRI plus cetuximab in first-line exhibited a significantly higher response rate and enhanced early tumor shrinkage in the interim analysis than the RAS-mutations population, as well as a high rate of secondary metastatic resections. Conclusion: Initial results of this new biomarker panel (quintuple-wildtype) are promising for anti-EGFR therapy with cetuximab plus doublet chemotherapy (FOLFIRI) in first-line treatment of metastatic CRC. These results warrant confirmation with higher case numbers in the IVOPAK II trial.
- Published
- 2021
- Full Text
- View/download PDF
19. Abdominelles Kompartmentsyndrom
- Author
-
Katharina Grass and Stephan Kersting
- Subjects
03 medical and health sciences ,0302 clinical medicine ,030208 emergency & critical care medicine ,030212 general & internal medicine ,General Medicine - Abstract
ZusammenfassungDas abdominelle Kompartmentsyndrom (ACS) ist ein lebensbedrohliches Krankheitsbild, dessen Behandlungserfolg insbesondere von einer zeitnahen zielführenden Diagnostik und adäquaten Behandlungsprinzipien abhängt. Dieser CME-Beitrag beschreibt die pathophysiologischen Vorgänge beim ACS sowie das diagnostische und therapeutische Vorgehen bei diesen schwerst gefährdeten, intensivpflichtigen Patienten.
- Published
- 2021
- Full Text
- View/download PDF
20. Gas plasma–oxidized sodium chloride acts via hydrogen peroxide in a model of peritoneal carcinomatosis
- Author
-
Lea Miebach, Eric Freund, Ramona Clemen, Stephan Kersting, Lars-Ivo Partecke, and Sander Bekeschus
- Subjects
Multidisciplinary ,Plasma Gases ,ICD ,ROS ,Chick Embryo ,Hydrogen Peroxide ,immunogenicity ,plasma medicine ,Sodium Chloride ,Reactive Nitrogen Species ,calreticulin ,Mice ,Cell Line, Tumor ,Animals ,Reactive Oxygen Species ,Peritoneal Neoplasms - Abstract
Gas plasma technology generates reactive oxygen and nitrogen species (ROS/RNS), inducing lethal oxidative damage in tumor cells. The transfer of gas plasma–derived ROS/RNS into liquids has been proposed as an innovative anti-cancer strategy targeting peritoneal carcinomatosis (PC). However, the mechanism of action is under debate. To this end, we compared gas plasma–oxidized medical-grade sodium chloride (oxNaCl) with a concentration-matched control (cmc) of NaCl enriched with equivalent concentrations of H 2 O 2 and NO 3 − in several cell lines and models of PC. Strikingly, oxNaCl and cmc performed equally well in oxidation and cytotoxic activity in tumor cells in two-dimensional cultures, three-dimensional (3D) tumor spheroids, vascularized 3D tumors grown on chicken-embryo chorioallantoic membranes, and a syngeneic PC mouse model in vivo. Given the importance of immunotherapies in oncology today, we focused on immunological consequences of the treatment. Again, to a similar extent, oxNaCl and cmc increased tumor cell immunogenicity and enhanced uptake by and maturation of peripheral blood monocyte–derived dendritic cells together with an inflammatory secretion profile. Furthermore, NanoString gene expression profiling revealed immune system processes and unfolded protein response-related pathways as being linked to the observed anti-tumor effects for both oxNaCl and cmc. In conclusion, gas plasma–generated oxNaCl and cmc showed equal therapeutic efficacy in our PC-related models. In light of the many promising anti-cancer studies of gas plasma–oxidized liquids and the convenient production of corresponding cmcs in large quantities as needed in clinics, our findings may spur research lines based on low-dose oxidants in peritoneal cancer therapy.
- Published
- 2022
- Full Text
- View/download PDF
21. Palliativchirurgie beim kolorektalen Karzinom – welche Faktoren können bei der Wahl des operativen Vorgehens helfen?
- Author
-
Tina Thomas, Stephan Kersting, Oliver Stöltzing, Jörg Schubert, Axel Denz, and R. Konopke
- Subjects
Gynecology ,medicine.medical_specialty ,business.industry ,medicine ,Surgery ,business - Abstract
Zusammenfassung Hintergrund Das chirurgische Vorgehen beim kolorektalen Karzinom (KRK) in der Palliativsituation lässt sich nur unzureichend standardisieren. Die vorliegende Studie wurde zur Identifikation von Kriterien für den Entscheid hinsichtlich Resektion des Malignoms mit oder ohne primäre Anastomose initiiert. Patienten/Material und Methoden In einer unizentrischen retrospektiven Analyse wurden 103 Patienten nach palliativer Resektion eines KRK mit oder ohne zeitgleiche Anastomose untersucht. Durch univariate und logistische Regressionsanalyse erfolgte die Beurteilung des Einflusses von insgesamt 40 Faktoren auf die postoperative Morbidität und Mortalität. Ergebnisse In 46 Fällen wurde eine Darmresektion mit primärer Anastomose, in 57 Fällen eine Diskontinuitätsresektion durchgeführt. Die postoperative Morbidität betrug insgesamt 44,7%, die Letalität 17,5%. Nach einzeitiger Resektion und Anastomose erhöhte ein Nikotinabusus (OR 4,2; p = 0,044), eine Hypalbuminämie (OR 4,0; p = 0,012), eine Kachexie (OR 3,9; p = 0,034), ein ASA-Score > 2 (OR 3,7; p = 0,030) und ein(e) Leberumbau/-zirrhose (OR 3,6; p = 0,031) das Risiko für postoperative Komplikationen. Die Hypalbuminämie (OR 1,8; p = 0,036), Kachexie (OR 1,8; p = 0,043), Anämie (OR 1,5; p = 0,038) und ein bekannter Alkoholabusus (OR 1,9; p = 0,023) wurden als unabhängige Risikofaktoren für die frühpostoperative Mortalität identifiziert. Nach Diskontinuitätsresektion führten eine Niereninsuffizienz (OR 2,1; p = 0,042) und Kachexie (OR 1,5; p = 0,045) zum signifikanten Anstieg des Risikos für die postoperative Morbidität, ein Alkoholabusus (OR 1,8; p = 0,041) für die Letalität. Eine Hypalbuminämie (OR 2,8; p = 0,019) und ein ASA-Score > 2 (OR 2,6; p = 0,004) steigerten nach Resektion und Rekonstruktion das Risiko für Majorkomplikationen entsprechend Clavien-Dindo, eine vorbestehende Niereninsuffizienz (OR 1,6; p = 0,023) das Risiko nach Diskontinuitätsresektion. In der univariaten Analyse wurden nach Tumorresektion und Rekonstruktion zusätzlich noch ein ASA-Score > 2 (p = 0,038), in beiden Gruppen mit und ohne primäre Anastomose eine dringliche Operation als signifikante Parameter mit Einfluss auf die Letalität ermittelt (p = 0,010 und p = 0,017). Schlussfolgerung Palliative Resektionen kolorektaler Karzinome haben eine hohe Morbidität und Mortalität. Bei vorbestehendem Alkoholabusus und dringlicher Operationsindikation sollte ein intensiveres Monitoring erfolgen. Bei Anämie, Kachexie, Hypalbuminämie sowie ASA-Score > 2 stellt möglicherweise die Diskontinuitätsresektion den geeigneteren Eingriff dar.
- Published
- 2020
- Full Text
- View/download PDF
22. Lokale Therapieverfahren beim oligometastasierten kolorektalen Karzinom
- Author
-
Stephan Kersting and Robert Grützmann
- Subjects
0301 basic medicine ,Gynecology ,03 medical and health sciences ,medicine.medical_specialty ,030104 developmental biology ,0302 clinical medicine ,Oncology ,business.industry ,030220 oncology & carcinogenesis ,Medicine ,Hematology ,business - Abstract
Das kolorektale Karzinom (KRK) ist eine der haufigsten malignen Erkrankungen. In den letzten Jahren hat sich das klinische Outcome von Patienten mit metastasiertem KRK stark verbessert. Dies ist auf einen dank verbesserter chirurgischer Techniken erhohten Anteil an Resektionen, auf verbesserte Chemotherapeutika, eine Ausweitung des Einsatzes ablativer Techniken und insbesondere ein intensiveres Management der Tumorerkrankung an sich zuruckzufuhren. Dies spiegelt sich in der zunehmenden Zahl der Patienten wider, die in einem multidisziplinaren Teamumfeld und in spezialisierten Krebszentren betreut werden. Weitere Verbesserungen finden sich in den bildgebenden Verfahren, aber auch bei prognostischen und pradiktiven molekularen Markern. Behandlungsentscheidungen fur Patienten mit metastasiertem KRK sollten evidenzbasiert getroffen werden. Hierzu muss die gesamte „Toolbox“ der lokalen Therapieverfahren bekannt und verfugbar sein und interdisziplinar immer wieder neu diskutiert werden.
- Published
- 2020
- Full Text
- View/download PDF
23. Der 'critical view of safety' zur Vermeidung von Gallengangskomplikationen bei der laparoskopischen Cholezystektomie
- Author
-
Stephan Kersting, Katharina Grass, and Karin Oeckl
- Subjects
Gynecology ,medicine.medical_specialty ,business.industry ,medicine ,Surgery ,business - Abstract
ZusammenfassungDie laparoskopische Cholezystektomie ist eine der am häufigsten durchgeführten Operationen weltweit. Gerade aufgrund der hohen Fallzahlen bleibt die iatrogene Verletzung des Ductus choledochus, so selten sie ist, ein nicht zu unterschätzendes Risiko des Eingriffs. Im Laufe der Jahre wurden unterschiedliche Methoden beschrieben, diese schwerwiegende Komplikation mit ihrer hohen Morbidität und sogar Mortalität zu vermeiden. Eine der sichersten Methoden der Vermeidung von Gallengangsläsionen ist die Etablierung des sog. „critical view of safety“ vor Durchtrennung jeglicher Strukturen, der in diesem Lehrvideo demonstriert werden soll.
- Published
- 2020
- Full Text
- View/download PDF
24. Referenz Allgemein- und Viszeralchirurgie – Pankreas
- Author
-
Ekaterina Petrova, Marianne Pavel, Michael Uder, Abbas Agaimy, Katja Fechner, Robert Grützmann, Marko Damm, Uwe Will, Georg F. Weber, Ulrich F. Wellner, Jürgen Siebler, Anke Mittelstädt, Helena Reitberger, Mohammad Rahbari, Deike Strobel, Felix Rückert, Norbert Meidenbauer, Stephan Kersting, Patrick Michl, Justus Baecker, Maximilian Brunner, Matthias Maak, Tobias Keck, Judith Büstgens, Jonas Rosendahl, Christian Krautz, and Daniel Eckhardt
- Published
- 2022
- Full Text
- View/download PDF
25. Neoadjuvant concurrent chemoradiotherapy with and without hyperthermia in retroperitoneal sarcomas: feasibility, efficacy, toxicity, and long-term outcome
- Author
-
Markus Eckstein, Norbert Meidenbauer, Udo S. Gaipl, Oliver J. Ott, Robert Grützmann, Sabine Semrau, Rainer Fietkau, Florian Putz, Florian Haller, Katja Fechner, Stephan Kersting, Abbas Agaimy, and Alexander Willner
- Subjects
Leiomyosarcoma ,medicine.medical_specialty ,medicine.medical_treatment ,Liposarcoma ,Leukocytopenia ,Thermotherapy ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Doxorubicin ,Ifosfamide ,ddc:610 ,Chemotherapy ,business.industry ,Doxorubicine ,Sarcoma ,Chemoradiotherapy ,Hyperthermia, Induced ,medicine.disease ,Neoadjuvant Therapy ,Radiation therapy ,Treatment Outcome ,Oncology ,Feasibility Studies ,Original Article ,Radiology ,business ,medicine.drug - Abstract
Purpose Retroperitoneal (RPS) sarcomas are associated with poor local and abdominal tumor control. However, the benefit of preoperative radio- or chemotherapy alone for these entities is currently unclear. Moreover, as intermediate- and high-grade sarcomas have a tendency toward early metastasis, exploration of neoadjuvant strategies is of high importance. This analysis reports the results of our 20-year single-institution experience with preoperative neoadjuvant concurrent chemoradiation. Methods From 2000–2019, 27 patients with intermediate- or high-grade RPS (12 dedifferentiated liposarcoma, 10 leiomyosarcoma, 5 others) were treated with radiotherapy (median dose: 50.4 Gy; range 45–75 Gy) and two cycles of chemotherapy (doxorubicin 50 mg/m2 BSA/d3 q28 and ifosfamide 1.5 g/m2 BSA/d1‑5 q28) in neoadjuvant intent. Chemotherapy consisted of doxorubicin alone in two cases and ifosfamide alone in one case. Fifteen patients (56%) additionally received deep regional hyperthermia. Results The median follow-up time was 53 months (±56.7 months). 92% of patients received two cycles of chemotherapy as planned and 92% underwent surgery. At 5 and 10 years, abdominal-recurrence-free survival was 74.6% (±10.1%) and 66.3% (±11.9%), distant metastasis-free survival was 67.2% (±9.7%) and 59.7% (±11.1%), and overall survival was 60.3% (±10.5%) and 60.3% (±10.5%), respectively. CTC grade III and IV toxicities were leukocytopenia (85%), thrombocytopenia (33%), and anemia (11%). There were no treatment-related deaths. Conclusion Neoadjuvant chemoradiotherapy with and without hyperthermia for retroperitoneal sarcomas is feasible and provided high local control of intermediate- and high-grade sarcoma.
- Published
- 2021
26. Mechanisms of Physical Plasma-Incuded Blood Coagualtion: What Happens at the Treatment-Interface?
- Author
-
Broder Poschkamp, Stephan Kersting, Thomas von Woedtke, Klaus-Dieter Weltmann, Sander Bekeschus, and Julia van der Linde
- Subjects
Red blood cell ,medicine.anatomical_structure ,Coagulation ,Chemistry ,Hemostasis ,medicine ,Platelet ,Hemoglobin ,Platelet activation ,Pharmacology ,medicine.disease ,Hemolysis ,Whole blood - Abstract
Major blood loss is a risk factor during surgery. Electrocauterization is frequently applied for necrotizing the tissue and thereby stops bleeding (hemostasis). However, the burned tissue is prone to detaching, generating the risk of internal bleeding after surgery. Plasma treatment might be an alternative to efficient hemostasis, which we have previously demonstrated in a mouse model and in human donor blood 1,2 . However, the underlying mechanisms have not been yet elucidated. We found plasma treatment to efficiently coagulated anticoagulated donor blood, which resulted from the local lysis of red blood cells (hemolysis) 3 . Using image cytometry further showed enhanced platelet aggregation. The plasma jet kINPen was used, which releases reactive oxygen species (ROS), but neither scavenging of long-lived ROS nor addition of chemically-generated ROS were able to abrogate or recapitulate the gas plasma effect. Yet, platelet activation was markedly impaired in platelet-rich plasma when compared to plasma-treated whole blood that moreover contained significant amounts of hemoglobin indicative of red blood cell lysis (hemolysis). Interestingly, incubation of whole blood with concentration-matched hemolysates phenocopied the plasmas-mediated platelet activation. Hence, we identified hemolysis being the main mechanism of plasma-induced blood coagulation via platelet activation.
- Published
- 2021
- Full Text
- View/download PDF
27. The microbiome in PDAC- more than microbiomania
- Author
-
S Wirtz, Jonel Trebicka, Robert Grützmann, M Langheinrich, Stephan Kersting, and Maximilian Brunner
- Subjects
Microbiome - Published
- 2021
- Full Text
- View/download PDF
28. MiR-132 controls pancreatic beta cell proliferation and survival through Pten/Akt/Foxo3 signaling
- Author
-
Johanna McChord, Katharina Ganss, Christian Krautz, Sebastian Hempel, Klaus-Peter Knoch, Michele Solimena, Robert Grützmann, Philippe Ravassard, Kamal Chowdhury, Jürgen Weitz, Stephan Kersting, Christian Pilarsky, Hassan Mziaut, Steffen Wolk, Georg Henniger, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Technische Universität Dresden = Dresden University of Technology (TU Dresden), Max-Planck-Institut für Biophysikalische Chemie - Max Planck Institute for Biophysical Chemistry [Göttingen], Max-Planck-Gesellschaft, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), and Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG)
- Subjects
Male ,0301 basic medicine ,Pten, phosphatase and tensin homolog ,Pi3k, phosphatidylinositol-4,5-bisphosphate 3-kinase ,Apoptosis ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,miR-132, microRNA 132 ,miR-132 ,Creb, cAMP response element-binding protein ,BrdU, bromodeoxyuridine ,Mice ,0302 clinical medicine ,Insulin-Secreting Cells ,miRNA, microRNA ,Raf, rapidly accelerated fibrosarcoma ,Cells, Cultured ,Mice, Knockout ,Gene knockdown ,Forkhead Box Protein O3 ,FOXO3 ,Original Article ,β cell regeneration ,Beta cell ,Signal Transduction ,lcsh:Internal medicine ,Cell Survival ,T2D, type 2 diabetes ,030209 endocrinology & metabolism ,Biology ,Fgfr3, fibroblast growth factor receptor 3 ,GSIS, glucose-stimulated insulin secretion ,03 medical and health sciences ,RT-PCR, reverse transcription polymerase chain reaction ,Pancreatectomy ,Nras, neuroblastoma RAS viral oncogene homolog ,Downregulation and upregulation ,Pten/Akt/Foxo3a ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,microRNA ,Animals ,Humans ,PTEN ,Gnb, G protein subunit beta ,lcsh:RC31-1245 ,Molecular Biology ,Protein kinase B ,Gnb1, G protein subunit beta 1 ,IPA, Ingenuity Pathway Analysis ,Cell Proliferation ,Mir-132 ,Beta Cell Regeneration ,Pten/akt/foxo3a ,pHH3, phosphohistone H3 ,Mapk1, mitogen-activated protein kinase 1 ,PTEN Phosphohydrolase ,Cell Biology ,LCM, laser capture microscopy ,Mice, Inbred C57BL ,MicroRNAs ,HEK293 Cells ,030104 developmental biology ,Ras, rat sarcoma ,Pik3r1, phosphoinositide-3 kinase regulatory subunit 1 ,Akt, protein kinase B ,Cancer research ,biology.protein ,Foxo3a, Forkhead box O3a ,Sos1, Son of Sevenless homolog 1 ,Proto-Oncogene Proteins c-akt - Abstract
Objective MicroRNAs (miRNAs) play an integral role in maintaining beta cell function and identity. Deciphering their targets and precise role, however, remains challenging. In this study, we aimed to identify miRNAs and their downstream targets involved in the regeneration of islet beta cells following partial pancreatectomy in mice. Methods RNA from laser capture microdissected (LCM) islets of partially pancreatectomized and sham-operated mice were profiled with microarrays to identify putative miRNAs implicated in beta cell regeneration. Altered expression of the selected miRNAs, including miR-132, was verified by RT-PCR. Potential targets of miR-132 were selected through bioinformatic data mining. Predicted miR-132 targets were validated for their changed RNA, protein expression levels, and signaling upon miR-132 knockdown and/or overexpression in mouse MIN6 and human EndoC-βH1 insulinoma cells. The ability of miR-132 to foster beta cell proliferation in vivo was further assessed in pancreatectomized miR-132−/− and control mice. Results Partial pancreatectomy significantly increased the number of BrdU+/insulin+ islet cells. Microarray profiling revealed that 14 miRNAs, including miR-132 and -141, were significantly upregulated in the LCM islets of the partially pancreatectomized mice compared to the LCM islets of the control mice. In the same comparison, miR-760 was the only downregulated miRNA. The changed expression of these miRNAs in the islets of the partially pancreatectomized mice was confirmed by RT-PCR only in the case of miR-132 and -141. Based on previous knowledge of its function, we focused our attention on miR-132. Downregulation of miR-132 reduced the proliferation of MIN6 cells while enhancing the levels of pro-apoptotic cleaved caspase-9. The opposite was observed in miR-132 overexpressing MIN6 cells. Microarray profiling, RT-PCR, and immunoblotting of the latter cells demonstrated their downregulated expression of Pten with concomitant increased levels of pro-proliferative factors phospho-Akt and phospho-Creb and inactivation of pro-apoptotic Foxo3a via its phosphorylation. Downregulation of Pten was further confirmed in the LCM islets of pancreatectomized mice compared to the sham-operated mice. Moreover, overexpression of miR-132 correlated with increased proliferation of EndoC-βH1 cells. The regeneration of beta cells following partial pancreatectomy was lower in the miR-132/212−/− mice than the control littermates. Conclusions This study provides compelling evidence about the critical role of miR-132 for the regeneration of mouse islet beta cells through the downregulation of its target Pten. Hence, the miR-132/Pten/Akt/Foxo3 signaling pathway may represent a suitable target to enhance beta cell mass., Highlights • miR-132 is induced in mouse islets upon partial pancreatectomy. • miR-132 promotes regeneration of β-cells in vivo following partial pancreatectomy. • miR-132 fosters in vitro proliferation/survival through Pten/Akt/Foxo3 signaling. • Downstream targets of miR-132 were identified in pancreatic β-cells. • miR-132−/− mice have impaired β-cell proliferation.
- Published
- 2020
- Full Text
- View/download PDF
29. Blood Glucose Homeostasis in the Course of Partial Pancreatectomy--Evidence for Surgically Reversible Diabetes Induced by Cholestasis.
- Author
-
Florian Ehehalt, Dorothée Sturm, Manuela Rösler, Marius Distler, Jürgen Weitz, Stephan Kersting, Barbara Ludwig, Uta Schwanebeck, Hans-Detlev Saeger, Michele Solimena, and Robert Grützmann
- Subjects
Medicine ,Science - Abstract
Partial pancreatic resection is accompanied not only by a reduction in the islet cell mass but also by a variety of other factors that are likely to interfere with glucose metabolism. The aim of this work was to characterize the patient dynamics of blood glucose homeostasis during the course of partial pancreatic resection and to specify the associated clinico-pathological variables.In total, 84 individuals undergoing elective partial pancreatic resection were consecutively recruited into this observational trial. The individuals were assigned based on their fasting glucose or oral glucose tolerance testing results into one of the following groups: (I) deteriorated, (II) stable or (III) improved glucose homeostasis three months after surgery. Co-variables associated with blood glucose dynamics were identified.Of the 84 participants, 25 (30%) displayed a normal oGTT, 17 (20%) showed impaired glucose tolerance, and 10 (12%) exhibited pathological glucose tolerance. Elevated fasting glucose was present in 32 (38%) individuals before partial pancreatic resection. Three months after partial pancreatic resection, 14 (17%) patients deteriorated, 16 (19%) improved, and 54 (64%) retained stable glucose homeostasis. Stability and improvement was associated with tumor resection and postoperative normalization of recently diagnosed glucose dysregulation, preoperatively elevated tumor markers and markers for common bile duct obstruction, acute pancreatitis and liver cell damage. Improvement was linked to preoperatively elevated insulin resistance, which normalized after resection and was accompanied by a decrease in fasting- and glucose-stimulated insulin secretion.Surgically reversible blood glucose dysregulation diagnosed concomitantly with a (peri-) pancreatic tumor appears secondary to compromised liver function due to tumor compression of the common bile duct and the subsequent increase in insulin resistance. It can be categorized as "cholestasis-induced diabetes" and thereby distinguished from other forms of hyperglycemic disorders.
- Published
- 2015
- Full Text
- View/download PDF
30. Risk factors for appendiceal neoplasm and malignancy among patients with acute appendicitis
- Author
-
Robert Grützmann, Christian Krautz, Justus Baecker, Matthias Maak, Philipp Lapins, Georg F. Weber, Stephan Kersting, Maximilian Brunner, and Melanie Langheinrich
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Perforation (oil well) ,Malignancy ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Preoperative Care ,medicine ,Appendectomy ,Humans ,Neoplasm ,Abscess ,Aged ,Aged, 80 and over ,Postoperative Care ,Univariate analysis ,business.industry ,Gastroenterology ,Middle Aged ,Hepatology ,Appendicitis ,medicine.disease ,Appendix ,medicine.anatomical_structure ,Appendiceal Neoplasms ,030220 oncology & carcinogenesis ,Acute Disease ,Multivariate Analysis ,Female ,030211 gastroenterology & hepatology ,Radiology ,business - Abstract
Non-operative management of acute uncomplicated appendicitis has shown promising results but might carry the risk of delayed diagnosis of premalignant or malignant appendiceal tumors found by chance in 0.7–2.5% of appendiceal specimen after appendectomy. Purpose of this study was to analyze whether appendiceal tumors are associated with a complicated appendicitis and to determine risk factors for appendiceal neoplasm and malignancy in patients with acute appendicitis. We performed a retrospective analysis of 1033 adult patients, who underwent appendectomy for acute appendicitis from 2010 to 2016 at the University hospital Erlangen. Data included patients’ demographics; comorbidities; pre-, intra- and postoperative findings; and histopathological results. Complicated appendicitis was defined in the presence of perforation or abscess. Appendiceal neoplasm respectively malignancy rate was 2.8% respectively 1.5%. Using univariate analysis, we identified seven risk factors at least for appendiceal neoplasm or malignancy: age, ASA, C-reactive protein, appendiceal diameter, perforation, intraoperative perithyphilitic abscess, and complicated appendicitis. Risk for appendiceal neoplasm or malignancy was 4.4% respectively 2.7% in complicated acute appendicitis compared to 2.0% respectively 1.0% in uncomplicated appendicitis (p = 0.043 respectively p = 0.060). In multivariate analysis, age ≥ 50 years and a diameter of the appendix in the sonography ≥ 13 mm were independent risk factors predicting the presence of appendiceal neoplasm and malignancy. Among patients with appendicitis, there are relevant risk factors predicting appendiceal tumors, especially age and appendiceal diameter in sonography. But the identified risk factors have a low sensitivity and specificity, so obtaining a confident preoperative diagnosis is challenging.
- Published
- 2019
- Full Text
- View/download PDF
31. Laparoskopische Hemikolektomie rechts mit kompletter mesokolischer Exzision (CME)
- Author
-
Klaus Weber, Felix Wiesmüller, Matthias Maak, Georg F. Weber, Christian Krautz, Maximilian Brunner, Stephan Kersting, and Robert Grützmann
- Subjects
Gynecology ,03 medical and health sciences ,medicine.medical_specialty ,0302 clinical medicine ,Colon carcinoma ,business.industry ,030220 oncology & carcinogenesis ,Medicine ,030211 gastroenterology & hepatology ,Surgery ,business ,Laparoscopic right hemicolectomy - Abstract
Zusammenfassung Einleitung Die komplette mesokolische Exzision (CME) gehört laut der deutschen S3-Leitlinie bei onkologischen Kolonresektionen zur Guten Klinischen Praxis (GCP, Good Clinical Practice). Diese Empfehlung basiert auf der Evidenz, dass die Entfernung des onkologisch relevanten Mesokolons ohne Verletzung der strukturellen Integrität sowie die zentrale vaskuläre Ligatur mit radikaler Lymphknotendissektion im Rahmen von CME-Kolonresektionen mit besseren histopathologischen Qualitätskriterien und besseren onkologischen Ergebnissen im Vergleich zu konventionellen Kolonresektionen einhergehen. Allerdings weisen Kolonresektionen mit CME besonders im rechten Hemikolon durch die anatomische Nähe zu Magen, Duodenum und Pankreas und einer hohen Variabilität der Gefäßstrukturen (z. B. des Truncus Henle) eine höhere Komplexität auf. Um die Sicherheit von laparoskopischen Hemikolektomien rechts mit CME zu erhöhen und die Weiterbildung dieses Eingriffes sicher und strukturiert zu ermöglichen, wurde von einer deutschen Expertengruppe für die laparoskopische Hemikolektomie rechts ein standardisiertes Vorgehen mit Sicherheitsblicken entwickelt. Im folgenden Video wird die Durchführung einer Hemikolektomie rechts mit CME gemäß dem von der Deutschen Expertengruppe Lap-CME erstbeschriebenen Konzept dargestellt. Indikation Karzinom des Colon ascendens. Prozedur Laparoskopische Hemikolektomie rechts mit kompletter mesokolischer Exzision (CME). Schlussfolgerung Die vorgeschlagene Standardisierung der laparoskopischen Hemikolektomie rechts mit CME nimmt die erhöhte Komplexität der Operation auf und strukturiert sie in wohldefinierte Schritte mit kritischen Sicherheitsblicken als Kontrollinstanzen, was zu einer Minimierung intraoperativer Komplikationen und einer erhöhten Sicherheit für den Patienten sowie zu einer Verbesserung der strukturierten Weiterbildung führen dürfte.
- Published
- 2019
- Full Text
- View/download PDF
32. Lehrfilm Facharztweiterbildung: Hemithyreoidektomie mit Neuromonitoring des N. laryngeus recurrens
- Author
-
Georg F. Weber, Robert Grützmann, Katja Linke, Stephan Kersting, Hannah Bleichroth, Maximilian Brunner, and Christian Krautz
- Subjects
Gynecology ,03 medical and health sciences ,medicine.medical_specialty ,0302 clinical medicine ,business.industry ,030220 oncology & carcinogenesis ,Thyroid malignancy ,medicine ,Surgery ,business ,030218 nuclear medicine & medical imaging - Abstract
Zusammenfassung Einleitung Die Prävalenz von Schilddrüsenknoten im Erwachsenenalter liegt durchschnittlich bei etwa 20% und nimmt mit zunehmendem Alter zu. Bei einem Großteil der Schilddrüsenknoten handelt es sich um benigne Veränderungen, nur selten liegen maligne Befunde vor. Allerdings kann die endgültige Dignität nicht selten erst nach erfolgter Resektion bestimmt werden. Wichtig ist daher eine komplikationsarme Operationstechnik. Standard der Resektion und Weiterbildungseingriff ist bei allen publizierten minimalinvasiven Techniken die offene Operation über einen Kocher-Kragenschnitt. Diese Technik soll in diesem Lehrvideo Schritt für Schritt dargestellt werden. Indikation Sonografisch und MIBI-szintigrafisch malignitätsverdächtiger solitärer Knoten im rechten Schilddrüsenlappen. Prozedur Hemithyreoidektomie rechts mit Neuromonitoring des N. laryngeus recurrens. Schlussfolgerung Bei solitärem malignitätsverdächtigen Schilddrüsenknoten stellt die Hemithyreoidektomie die adäquate primäre Therapie dar. Die Verwendung eines intraoperativen Neuromonitorings zur sicheren Identifikation und Schonung des N. laryngeus recurrens, die Darstellung und Schonung der Nebenschilddrüsen ohne Kompromittierung der Durchblutung sowie eine sorgfältige Blutstillung stellen die wichtigsten Pfeiler einer risikoarmen Operation an der Schilddrüse dar.
- Published
- 2019
- Full Text
- View/download PDF
33. IFN-γ drives inflammatory bowel disease pathogenesis through VE-cadherin–directed vascular barrier disruption
- Author
-
Michael Stürzl, Daniela Regensburger, Thomas Wohlfahrt, Viktoria Kramer, Noo Li Jeon, Eugenia Vivi, Somin Lee, Victoria Langer, Nathalie Britzen-Laurent, Lisa Skottke, Christoph Becker, Timo Rath, Ralf H. Adams, Karina Suchowski, Andreas Ramming, Benjamin Schmid, Philipp Tripal, Elisabeth Naschberger, Stephan Kersting, Carol Geppert, Claudia Handtrack, Michael Schumann, Thomas Winkler, and Maximilian J. Waldner
- Subjects
Adult ,Male ,0301 basic medicine ,Vascular permeability ,Inflammation ,Context (language use) ,Inflammatory bowel disease ,Pathogenesis ,Adherens junction ,Interferon-gamma ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Antigens, CD ,medicine ,Animals ,Humans ,Colitis ,Aged ,Mice, Knockout ,business.industry ,Endothelial Cells ,Adherens Junctions ,General Medicine ,Middle Aged ,Cadherins ,Inflammatory Bowel Diseases ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Imatinib Mesylate ,Cancer research ,Female ,medicine.symptom ,VE-cadherin ,business ,Research Article - Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with rising incidence. Diseased tissues are heavily vascularized. Surprisingly, the pathogenic impact of the vasculature in IBD and the underlying regulatory mechanisms remain largely unknown. IFN-γ is a major cytokine in IBD pathogenesis, but in the context of the disease, it is almost exclusively its immune-modulatory and epithelial cell-directed functions that have been considered. Recent studies by our group demonstrated that IFN-γ also exerts potent effects on blood vessels. Based on these considerations, we analyzed the vessel-directed pathogenic functions of IFN-γ and found that it drives IBD pathogenesis through vascular barrier disruption. Specifically, we show that inhibition of the IFN-γ response in vessels by endothelial-specific knockout of IFN-γ receptor 2 ameliorates experimentally induced colitis in mice. IFN-γ acts pathogenic by causing a breakdown of the vascular barrier through disruption of the adherens junction protein VE-cadherin. Notably, intestinal vascular barrier dysfunction was also confirmed in human IBD patients, supporting the clinical relevance of our findings. Treatment with imatinib restored VE-cadherin/adherens junctions, inhibited vascular permeability, and significantly reduced colonic inflammation in experimental colitis. Our findings inaugurate the pathogenic impact of IFN-γ-mediated intestinal vessel activation in IBD and open new avenues for vascular-directed treatment of this disease.
- Published
- 2019
- Full Text
- View/download PDF
34. Murine Macrophages Modulate Their Inflammatory Profile in Response to Gas Plasma-Inactivated Pancreatic Cancer Cells
- Author
-
Janik Riese, Lars-Ivo Partecke, Eric Freund, Stephan Kersting, Julia van der Linde, Aydar Khabipov, Andre Käding, Kim Rouven Liedtke, and Sander Bekeschus
- Subjects
Cancer Research ,Chemokine ,medicine.medical_treatment ,CCL4 ,PDA6606 ,Pancreatic cancer ,cold physical plasma ,medicine ,metastasis ,tumor microenvironment (TME) ,cold atmospheric pressure plasma ,RC254-282 ,biology ,Chemistry ,Communication ,kINPen ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Chemotaxis ,plasma medicine ,M2 Macrophage ,medicine.disease ,CAP ,CXCL1 ,Cytokine ,Oncology ,Cancer research ,biology.protein ,Plasma medicine - Abstract
Simple Summary Pancreatic cancer is a devastating disease with high mortality. The cancer is characterized by a dynamic and immunosuppressive tumor microenvironment (TME) with high numbers of macrophages. Gas plasma technology was previously suggested as a promising new tool in oncology and pancreatic cancer treatment. However, it is unclear how gas plasma-treated pancreatic cancer cells affect the phenotype and inflammatory profile of macrophages. Besides profound antitumor effects of gas plasma-exposed tumor cells, we identified in such co-cultures unique signatures of both pro- and anti-inflammatory mediators being secreted at elevated levels. These responses might be beneficial as they promote neither overshooting inflammation and metastasis nor immunosuppression, fueling tumor growth as a known consequence of anti-inflammation. Abstract Macrophages and immuno-modulation play a dominant role in the pathology of pancreatic cancer. Gas plasma is a technology recently suggested to demonstrate anticancer efficacy. To this end, two murine cell lines were employed to analyze the inflammatory consequences of plasma-treated pancreatic cancer cells (PDA) on macrophages using the kINPen plasma jet. Plasma treatment decreased the metabolic activity, viability, and migratory activity in an ROS- and treatment time-dependent manner in PDA cells in vitro. These results were confirmed in pancreatic tumors grown on chicken embryos in the TUM-CAM model (in ovo). PDA cells promote tumor-supporting M2 macrophage polarization and cluster formation. Plasma treatment of PDA cells abrogated this cluster formation with a mixed M1/M2 phenotype observed in such co-cultured macrophages. Multiplex chemokine and cytokine quantification showed a marked decrease of the neutrophil chemoattractant CXCL1, IL6, and the tumor growth supporting TGFβ and VEGF in plasma-treated compared to untreated co-culture settings. At the same time, macrophage-attractant CCL4 and MCP1 release were profoundly enhanced. These cellular and secretome data suggest that the plasma-inactivated PDA6606 cells modulate the inflammatory profile of murine RAW 264.7 macrophages favorably, which may support plasma cancer therapy.
- Published
- 2021
35. Neoadjuvant concurrent chemoradiotherapy with and without hyperthermia in retroperitoneal and intra-abdominal sarcomas: Feasibility, efficacy, toxicity and long-term outcome
- Author
-
Robert Grützmann, Rainer Fietkau, Florian Haller, Norbert Meidenbauer, Oliver J. Ott, Markus Eckstein, Sabine Semrau, Udo S. Gaipl, Florian Putz, Katja Fechner, Abbas Agaimy, Alexander Willner, and Stephan Kersting
- Subjects
Hyperthermia ,medicine.medical_specialty ,business.industry ,Toxicity ,medicine ,Radiology ,medicine.disease ,business ,Outcome (game theory) ,Term (time) ,Concurrent chemoradiotherapy - Abstract
Background Retroperitoneal (RPS) and intra-abdominal sarcomas (IAS) are associated with poor local and abdominal tumor control. Yet, the benefit of preoperative radio- or chemotherapy alone for these entities currently is unclear. Moreover, as intermediate- and high-grade sarcomas have a tendency for early metastasis, exploration of neoadjuvant strategies is of high importance. This analysis reports the results of our 20-year single-institution experience with preoperative neoadjuvant concurrent chemoradiation.Methods From 2000-2019, 27 patients with intermediate- or high-grade RPS or IAS (12 dedifferentiated liposarcoma, 10 leiomyosarcoma, 5 others) were treated with radiotherapy (median dose: 50.4 Gy; range 45-75 Gy) and two cycles of chemotherapy (doxorubicin 50mg/m² BSA/d3 q28 and ifosfamide 1.5g/m2 BSA/d1-5 q28) in neoadjuvant intention. Chemotherapy consisted of doxorubicin alone in two cases and ifosfamide alone in one case. Fifteen patients (56%) received deep regional hyperthermia additionally.Results The median follow-up time was 53 months (± 56.7 months). 92% of patients received two cycles of chemotherapy as planned and 92% underwent surgery. At 5 and 10 years, abdominal-recurrence-free-survival was 74.6% (± 10.1%) and 66.3% (± 11.9%), distant-metastasis-free-survival was 67.2% (± 9.7%) and 59.7% (± 11.1%), and overall-survival was 60.3% (± 10.5%) and 60.3% (± 10.5%), respectively. CTC grade III and IV toxicities were leukocytopenia (85%), thrombocytopenia (33%) and anemia (11%). There were no treatment-related deaths.Conclusions Neoadjuvant chemoradiotherapy with and without hyperthermia for retroperitoneal and intra-abdominal sarcoma is feasible and provided high local control of intermediate - and high-grade sarcoma.
- Published
- 2021
- Full Text
- View/download PDF
36. Results of isolated limb perfusion for metastasized malignant melanoma
- Author
-
Jonas Goehl, Vera Schellerer, Stephan Kersting, Thomas Foertsch, Michael Erdmann, Johannes Frenger, Susanne Merkel, and Robert Gruetzmann
- Subjects
Melphalan ,Adult ,Male ,medicine.medical_specialty ,Adolescent ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Tumor stage ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,In patient ,030212 general & internal medicine ,Neoplasm Metastasis ,Adverse effect ,Survival rate ,Melanoma diagnosis ,Melanoma ,Aged ,Retrospective Studies ,Aged, 80 and over ,Isolated limb perfusion ,business.industry ,Extremities ,Hyperthermia, Induced ,Middle Aged ,medicine.disease ,Prognosis ,Combined Modality Therapy ,Surgery ,Survival Rate ,Oncology ,030220 oncology & carcinogenesis ,Chemotherapy, Cancer, Regional Perfusion ,Female ,Neoplasm Recurrence, Local ,business ,medicine.drug ,Follow-Up Studies - Abstract
Background and objectives Locoregional metastases are typical biological manifestations of advanced malignant melanomas. Treatment with hyperthermic isolated limb perfusion (HILP) should be considered in affected patients. In the present study, we have analyzed the results of HILPs performed in our department. Patients and methods Eighty patients with locoregional metastases of the extremities received HILP at the Department of Surgery between January 2007 and December 2016. The mean follow-up was 38 months. Results The study included 50 men and 30 women (mean age: 63 years). The median time between melanoma diagnosis and HILP was 25 months (range: 1–219 months). HILP was performed in curative (n = 45) and palliative (n = 35) intention. Seventy-five patients received a drug combination of melphalan/dactinomycin and five patients received a drug combination of melphalan/tumor necrosis factor-alpha. Remission rates were determined in 72 of 80 patients (90%) as follows: partial response n = 28, complete response n = 25, no response n = 19. Of the 25 patients with complete response, 13 patients developed a new tumor manifestation during follow-up (locoregional recurrences n = 4; distant metastases n = 3; both n = 6). The median overall survival rate was 33 months. Tumor stage influenced the survival rate significantly (p = 0.001). Patients with complete response showed a significantly better overall survival than patients with partial or no response (p = 0.016). Conclusion HILP is an effective therapeutic option in patients with locoregional metastases. This procedure carries a certain risk of side effects and adverse events but overall results in good response rates. Therefore, HILP should be offered to selected patients based on an individual discussion, considering their health status and oncological prognosis.
- Published
- 2021
37. Google Goes Cancer: Improving Outcome Prediction for Cancer Patients by Network-Based Ranking of Marker Genes.
- Author
-
Christof Winter, Glen Kristiansen, Stephan Kersting, Janine Roy, Daniela Aust, Thomas Knösel, Petra Rümmele, Beatrix Jahnke, Vera Hentrich, Felix Rückert, Marco Niedergethmann, Wilko Weichert, Marcus Bahra, Hans J. Schlitt, Utz Settmacher, Helmut Friess, Markus W. Büchler, Hans-Detlev Saeger, Michael Schroeder 0001, Christian Pilarsky, and Robert Grützmann
- Published
- 2012
- Full Text
- View/download PDF
38. [Palliative Surgery in Colorectal Cancer - Which Factors Should Influence the Choice of the Surgical Procedure?]
- Author
-
Ralf, Konopke, Jörg, Schubert, Oliver, Stöltzing, Tina, Thomas, Stephan, Kersting, and Axel, Denz
- Subjects
Postoperative Complications ,Risk Factors ,Colonic Neoplasms ,Palliative Care ,Humans ,Colorectal Neoplasms ,Retrospective Studies - Abstract
The surgical procedure for patients with colorectal cancer (CRC) in the palliative situation cannot be adequately standardised. The present study was initiated to identify criteria for the decision for resection of the malignancy with or without anastomosis.In a unicentric retrospective analysis, 103 patients after palliative resection with or without anastomosis due to CRC were examined. Using univariate and logistic regression analysis, the influence of a total of 40 factors on postoperative morbidity and mortality was assessed.In 46 cases, resection with primary anastomosis and in 57 cases a discontinuity resection was performed. Postoperative morbidity was 44.7% and mortality 17.5%. After one-stage resection with anastomosis, nicotine abuse (OR 4.2; p = 0.044), hypalbuminaemia (OR 4.0; p = 0.012), ASA score 2 (OR 3.7; p = 0.030) and liver remodelling/cirrhosis (OR 3.6; p = 0.031) increased the risk for postoperative complications. Hypalbuminaemia (OR 1.8; p = 0.036), cachexia (OR 1.8; p = 0.043), anaemia (OR 1.5; p = 0.038) and known alcohol abuse (OR 1.9; p = 0.023) were identified as independent risk factors for early postoperative mortality. After discontinuity resection, renal failure (OR 2.1; p = 0.042) and cachexia (OR 1.5; p = 0.045) led to a significant increase in the risk of postoperative morbidity, alcohol abuse (OR 1.8; p = 0.041) in mortality. Hypalbuminaemia (OR 2.8; p = 0.019) and an ASA score 2 (OR 2.6; p = 0.004) after resection and reconstruction increased the risk of major complications according to Clavien-Dindo, while pre-existing renal failure (OR 1.6; p = 0.023) increased the risk after discontinuity resection. In univariate analysis, an ASA score 2 (p = 0.038) after simultaneous tumour resection and reconstruction, and urgent surgery in both groups with or without primary anastomosis were additionally identified as significant parameters with a negative influence on mortality (p = 0.010 and p = 0.017).Palliative resections of colorectal carcinomas have high morbidity and mortality. Especially in cases of pre-existing alcohol abuse and/or urgent indication for surgery, more intensive monitoring should be performed. In the case of anaemia, cachexia, hypalbuminemia and an ASA score 2, discontinuity resection may be the more appropriate procedure.Das chirurgische Vorgehen beim kolorektalen Karzinom (KRK) in der Palliativsituation lässt sich nur unzureichend standardisieren. Die vorliegende Studie wurde zur Identifikation von Kriterien für den Entscheid hinsichtlich Resektion des Malignoms mit oder ohne primäre Anastomose initiiert.In einer unizentrischen retrospektiven Analyse wurden 103 Patienten nach palliativer Resektion eines KRK mit oder ohne zeitgleiche Anastomose untersucht. Durch univariate und logistische Regressionsanalyse erfolgte die Beurteilung des Einflusses von insgesamt 40 Faktoren auf die postoperative Morbidität und Mortalität.In 46 Fällen wurde eine Darmresektion mit primärer Anastomose, in 57 Fällen eine Diskontinuitätsresektion durchgeführt. Die postoperative Morbidität betrug insgesamt 44,7%, die Letalität 17,5%. Nach einzeitiger Resektion und Anastomose erhöhte ein Nikotinabusus (OR 4,2; p = 0,044), eine Hypalbuminämie (OR 4,0; p = 0,012), eine Kachexie (OR 3,9; p = 0,034), ein ASA-Score 2 (OR 3,7; p = 0,030) und ein(e) Leberumbau/-zirrhose (OR 3,6; p = 0,031) das Risiko für postoperative Komplikationen. Die Hypalbuminämie (OR 1,8; p = 0,036), Kachexie (OR 1,8; p = 0,043), Anämie (OR 1,5; p = 0,038) und ein bekannter Alkoholabusus (OR 1,9; p = 0,023) wurden als unabhängige Risikofaktoren für die frühpostoperative Mortalität identifiziert. Nach Diskontinuitätsresektion führten eine Niereninsuffizienz (OR 2,1; p = 0,042) und Kachexie (OR 1,5; p = 0,045) zum signifikanten Anstieg des Risikos für die postoperative Morbidität, ein Alkoholabusus (OR 1,8; p = 0,041) für die Letalität. Eine Hypalbuminämie (OR 2,8; p = 0,019) und ein ASA-Score 2 (OR 2,6; p = 0,004) steigerten nach Resektion und Rekonstruktion das Risiko für Majorkomplikationen entsprechend Clavien-Dindo, eine vorbestehende Niereninsuffizienz (OR 1,6; p = 0,023) das Risiko nach Diskontinuitätsresektion. In der univariaten Analyse wurden nach Tumorresektion und Rekonstruktion zusätzlich noch ein ASA-Score 2 (p = 0,038), in beiden Gruppen mit und ohne primäre Anastomose eine dringliche Operation als signifikante Parameter mit Einfluss auf die Letalität ermittelt (p = 0,010 und p = 0,017).Palliative Resektionen kolorektaler Karzinome haben eine hohe Morbidität und Mortalität. Bei vorbestehendem Alkoholabusus und dringlicher Operationsindikation sollte ein intensiveres Monitoring erfolgen. Bei Anämie, Kachexie, Hypalbuminämie sowie ASA-Score 2 stellt möglicherweise die Diskontinuitätsresektion den geeigneteren Eingriff dar.
- Published
- 2020
39. Oncological colorectal surgery during the COVID-19pandemic—a national survey
- Author
-
Christian Krautz, Stefan Benz, Stephan Kersting, Benno Stinner, Georg F. Weber, Robert Grützmann, and Maximilian Brunner
- Subjects
Waiting time ,Surgical caseload ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Attitude of Health Personnel ,Colorectal cancer ,Pneumonia, Viral ,COVID-19 pandemic ,Health Services Accessibility ,03 medical and health sciences ,0302 clinical medicine ,Colorectal surgery ,Germany ,Humans ,Medicine ,ddc:610 ,Practice Patterns, Physicians' ,Oncological surgery ,Pandemics ,Digestive System Surgical Procedures ,Health policy ,Health Care Rationing ,business.industry ,SARS-CoV-2 infection ,Health Policy ,Surgical care ,General surgery ,Gastroenterology ,COVID-19 ,medicine.disease ,Health Care Surveys ,030220 oncology & carcinogenesis ,Original Article ,030211 gastroenterology & hepatology ,Colorectal Neoplasms ,Coronavirus Infections ,business ,Colorectal surgeons ,Federal state - Abstract
Purpose The aim of this study was to clarify the surgical supply situation of oncological colorectal patients in Germany during limitations of the OR caseload due to the COVID-19 pandemic. Methods Between 11th and 19th April 2020, all members of a consortium of German colorectal cancer centers were invited to participate in a web-based survey on the current status of surgical care situation of colorectal cancer patients in Germany. Results A total of 112 colorectal surgeons of 101 German hospitals participated in the survey. Eighty-seven percent of the participating hospitals had to reduce their total surgical caseload and 34% their surgical volume for oncological colorectal patients during COVID-19 pandemic. Restrictions of the surgical caseload were independent of the size of the hospital and the number of cases of COVID-19 in the federal state of the hospital. Sixteen percent of colorectal surgeons consider surgical limitations to be not justified and 78% to be justified only if the care of oncological patients is ensured. Ninety-five percent of the colorectal surgeons interviewed stated that all oncological colorectal patients with an indication for surgery should be operated in time, despite the current reservations for COVID-19 patients. For the majority of the respondents (63% and 51%, respectively), an extended waiting time for surgery of up to 2 weeks was acceptable for non-metastatic and metastatic patients, respectively. Conclusion In Germany, there is a temporarily relevant reduction of surgical volume in oncological colorectal patients. Most colorectal surgeons stated that oncological colorectal surgery should not be compromised despite the measures taken during the COVID-19 pandemic.
- Published
- 2020
40. Variation in Bile Microbiome by the Etiology of Cholestatic Liver Disease
- Author
-
Cristina Ortiz, Manimozhiyan Arumugam, Robert Schierwagen, Mads Israelsen, Christian Jansen, Tobias J. Weismüller, Olaf Tyc, Florence Servant, Wenyi Gu, Sandra Torres, Stephan Kersting, Jacob Nattermann, Michael Praktiknjo, Christian P. Strassburg, Sabine Klein, Melanie Langheinrich, Jonel Trebicka, Aleksander Krag, Frank Erhard Uschner, Benjamin Lelouvier, and Stefan Zeuzem
- Subjects
medicine.medical_treatment ,Liver transplantation ,Bile Acids and Salts ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Bile ,Humans ,Microbiome ,030304 developmental biology ,0303 health sciences ,Transplantation ,Cholestasis ,Hepatology ,business.industry ,Liver Diseases ,Microbiota ,Liver Transplantation ,Variation (linguistics) ,Liver ,Immunology ,Etiology ,030211 gastroenterology & hepatology ,Surgery ,Cholestatic liver disease ,business - Published
- 2020
- Full Text
- View/download PDF
41. Microbiome Patterns in Matched Bile, Duodenal, Pancreatic Tumor Tissue, Drainage, and Stool Samples: Association with Preoperative Stenting and Postoperative Pancreatic Fistula Development
- Author
-
Jonel Trebicka, Christian Krautz, Robert Grützmann, Robert Schierwagen, Barbara Kneis, Christian Pilarsky, Maximilian Brunner, Stefan Wirtz, Stephan Kersting, Abbas Agaimy, Matthias M Gittler, Georg F. Weber, Melanie Langheinrich, and Olaf Tyc
- Subjects
medicine.medical_specialty ,pancreatic cancer ,lcsh:Medicine ,microbiome ,Gastroenterology ,Article ,Lesion ,03 medical and health sciences ,0302 clinical medicine ,Pancreatic tumor ,Medizinische Fakultät ,Internal medicine ,Pancreatic cancer ,Biopsy ,postoperative complications ,medicine ,pancreatic surgery ,Microbiome ,ddc:610 ,030304 developmental biology ,0303 health sciences ,Common bile duct ,medicine.diagnostic_test ,Bile duct ,business.industry ,lcsh:R ,General Medicine ,medicine.disease ,16S rRNA sequencing ,medicine.anatomical_structure ,Pancreatic fistula ,030220 oncology & carcinogenesis ,medicine.symptom ,business - Abstract
Postoperative complications after pancreatic surgery are still a significant problem in clinical practice. The aim of this study was to characterize and compare the microbiomes of different body compartments (bile duct, duodenal mucosa, pancreatic tumor lesion, postoperative drainage fluid, and stool samples, preoperative and postoperative) in patients undergoing pancreatic surgery for suspected pancreatic cancer, and their association with relevant clinical factors (stent placement, pancreatic fistula, and gland texture). For this, solid (duodenal mucosa, pancreatic tumor tissue, stool) and liquid (bile, drainage fluid) biopsy samples of 10 patients were analyzed using 16s rRNA gene next-generation sequencing. Our analysis revealed: (i) a distinct microbiome in the different compartments, (ii) markedly higher abundance of Enterococcus in patients undergoing preoperative stent placement in the common bile duct, (iii) significant differences in the beta diversity between patients who developed a postoperative pancreatic fistula (POPF B/C), (iv) patients with POPF B/C were more likely to have bacteria belonging to the genus Enterococcus, and (v) differences in microbiome composition with regard to the pancreatic gland texture. The structure of the microbiome is distinctive in different compartments, and can be associated with the development of a postoperative pancreatic fistula.
- Published
- 2020
42. The bacterial bile microbiome and its role in liver diseases
- Author
-
Manimozhiyan Arumugam, Christian Jansen, Olaf Tyc, Stefan Zeuzem, Stephan Kersting, Christian P. Strassburg, Jonel Trebicka, Melanie Langheinrich, Mads Israelsen, W Gu, Frank Erhard Uschner, Benjamin Lelouvier, Cristina Ortiz, Aleksander Krag, Florence Servant, Sabine D. Klein, Robert Schierwagen, Jacob Nattermann, Sandra Torres, Tobias J. Weismüller, and Michael Praktiknjo
- Subjects
Microbiome ,Biology ,Microbiology - Published
- 2020
- Full Text
- View/download PDF
43. Predictive factors of early outcome after palliative surgery for colorectal carcinoma
- Author
-
Stephan Kersting, Jörg Schubert, R. Konopke, Oliver Stöltzing, Axel Denz, and Tina Thomas
- Subjects
medicine.medical_specialty ,RD1-811 ,business.industry ,Colorectal cancer ,General surgery ,palliative treatment ,colorectal cancer ,030230 surgery ,medicine.disease ,Outcome (game theory) ,Palliative surgery ,surgery ,03 medical and health sciences ,0302 clinical medicine ,palliative surgery ,030220 oncology & carcinogenesis ,medicine ,metastasis ,business ,Research Article - Abstract
Objectives A significant number of patients with colorectal cancer are presented with various conditions requiring surgery in an oncologically palliative setting. We performed this study to identify risk factors for early outcome after surgery to facilitate the decision-making process for therapy in a palliative disease. Methods We performed a retrospective chart review of 142 patients who underwent palliative surgery due to locally advanced, complicated, or advanced metastatic colorectal carcinoma between January 2010 and April 2018 at the “Elbland” Medical Center Riesa. We performed a logistic regression analysis of 43 factors to identify independent predictors for complications and mortality. Results Surgery included resections with primary anastomosis (n=31; 21.8%) or discontinuous resections with colostomy (n=38; 26.8%), internal bypasses (n=27; 19.0%) and stoma formation only (n=46; 32.4%). The median length of hospitalization was 12 days (2–53 days), in-hospital morbidity was 50.0% and the mortality rate was 18.3%. Independent risk factors of in-hospital morbidity were age (HR: 1.5, p=0.046) and various comorbidities of the patients [obesity (HR: 1.8, p=0.036), renal failure (HR: 1.6, p=0.040), diabetes (HR: 1.6, p=0.032), alcohol abuse (HR: 1.3, p=0.023)] as well as lung metastases (HR: 1.6, p=0.041). Arteriosclerosis (HR: 1.4; p=0.045) and arterial hypertension (HR: 1.4, p=0.042) were independent risk factors for medical complications in multivariate analysis. None of the analyzed factors predicted the surgical morbidity after the palliative procedures. Emergency surgery (HR: 10.2, p=0.019), intestinal obstruction (HR: 9.2, p=0.006) and ascites (HR: 5.0, p=0.034) were multivariate significant parameters of in-hospital mortality. Conclusions Palliatively treated patients with colorectal cancer undergoing surgery show high rates of morbidity and mortality after surgery. In this retrospective chart review, independent risk factors for morbidity and in-hospital mortality were identified that are similar to patients in curative care. An adequate selection of patients before palliative operation should lead to a better outcome after surgery. Especially in patients with intestinal obstruction and ascites scheduled for emergency surgery, every effort should be made to convey these patients to elective surgery by interventional therapy, such as a stent or minimally invasive stoma formation.
- Published
- 2020
44. The Prognostic Value of the Number of Harvested Negative Lymph Nodes in Patients Treated by Esophagectomy With or Without Neoadjuvant Chemoradiation
- Author
-
Christian Krautz, Stephan Kersting, Robert Grützmann, Susanne Merkel, Maximilian Brunner, and Georg F. Weber
- Subjects
Male ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Gastroenterology ,Internal medicine ,medicine ,Carcinoma ,Humans ,In patient ,Lymph node ,Retrospective Studies ,Preoperative chemoradiotherapy ,business.industry ,Significant difference ,General Medicine ,Chemoradiotherapy, Adjuvant ,medicine.disease ,Prognosis ,Survival Analysis ,Esophagectomy ,medicine.anatomical_structure ,Oncology ,Lymphadenectomy ,Female ,Lymph ,Lymph Nodes ,business - Abstract
Background/aim The prognostic value of the number of harvested negative lymph nodes (NLNs) in patients with node-negative esophageal carcinoma treated by esophagectomy with or without neoadjuvant chemoradiation is unclear. Patients and methods A total of 136 patients who underwent oncological esophagectomy with two-field lymphadenectomy from 1995 to 2014 were analyzed regarding the prognostic impact of NLNs. 86 patients received primary surgery (group 1) and 50 patients had preoperative chemoradiation followed by surgery (group 2). Results The 5-year overall survival (OS) was 61.1%. Median lymph node harvest was significantly higher in group 1 (39 vs. 34 in group 2, p=0.007). In group 1, patients with a higher number of negative lymph nodes (>40) had a better OS [57.6% vs. 78.9%, HR=0.5 (0.3-0.9), p=0.026], whereas there was no significant difference in group 2 using the same cutoff (47.6% vs. 66.7%, p=0.476). Conclusion The number of NLNs is an independent prognostic factor for patients with esophageal carcinoma treated by primary esophagectomy, but not in patients after neoadjuvant chemoradiation.
- Published
- 2020
45. Upregulation of CD20 Positive B-Cells and B-Cell Aggregates in the Tumor Infiltration Zone is Associated with Better Survival of Patients with Pancreatic Ductal Adenocarcinoma
- Author
-
Maximilian Brunner, Christian Krautz, Katharina Maier, Robert Grützmann, Stephan Kersting, Petra Rümmele, Georg F. Weber, Susanne Merkel, Anne Jacobsen, and Alan Bénard
- Subjects
Male ,0301 basic medicine ,Oncology ,medicine.medical_treatment ,lcsh:Chemistry ,0302 clinical medicine ,Tumor Microenvironment ,Medicine ,b-cells ,lcsh:QH301-705.5 ,Spectroscopy ,CD20 ,B-Lymphocytes ,biology ,General Medicine ,Middle Aged ,Prognosis ,Computer Science Applications ,Survival Rate ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Pancreatectomy ,Immunohistochemistry ,Adenocarcinoma ,Female ,Infiltration (medical) ,Carcinoma, Pancreatic Ductal ,medicine.medical_specialty ,Stromal cell ,pancreatic ductal adenocarcinoma ,b-cell aggregates ,survival ,Article ,Catalysis ,Inorganic Chemistry ,03 medical and health sciences ,Lymphocytes, Tumor-Infiltrating ,Internal medicine ,Humans ,ddc:610 ,Physical and Theoretical Chemistry ,Molecular Biology ,B cell ,Aged ,Tumor microenvironment ,business.industry ,Organic Chemistry ,cd20 ,Antigens, CD20 ,medicine.disease ,digestive system diseases ,Pancreatic Neoplasms ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,biology.protein ,business ,Follow-Up Studies - Abstract
Patients with pancreatic ductal adenocarcinoma (PDAC) normally have a poor long-term prognosis. However, some rare cases of long-term survivors have been reported. The tumor microenvironment, consisting of cellular and stromal components, possibly plays an important role and might influence prognosis. In this context, the role of tumor-infiltrating B-cells and its impact on the survival in patients with PDAC remains controversial. We therefore aimed to assess the prognostic value of CD20-positive B-cells and CD20-positive B-cell aggregates as well as CD138, IgM, Pax5, and Ki67 on the survival of patients with PDAC using immunohistochemistry of FFPE pancreatectomy tissue sections from patients that underwent primary surgery for pT3- and R0-pancreatic adenocarcinoma between 1995 and 2016. Patients with PDAC were matched and grouped in 16 long-term-survivors (LTS, median overall survival (OS): 96 months [range: 61&ndash, 177 months]) and 16 short-term-survivors (STS, median OS: 16 months [range: 7&ndash, 32 months]). CD20-positive B-cells and B-cell aggregates in the tumor infiltration zone were significantly upregulated in the LTS-group compared to the STS-group (p = 0.0499 respectively p = 0.0432). Regarding the entire patient cohort (n = 32) CD20 positive B-cell aggregates in the tumor infiltration zone were an independent prognostic marker for overall survival in multivariate analysis (HR 9.2, CI 1.6&ndash, 51.4, p = 0.012). These results underline the importance of tumor-associated B-cells for prognosis of patients with PDAC. The detailed role of B cells in the pathomechanism of PDAC should be further investigated for predicting outcome, identifying appropriate treatment regimens, and developing novel therapeutic options.
- Published
- 2020
46. [The Critical View of Safety to Avoid Biliary Complications in Laparoscopic Cholecystectomy]
- Author
-
Katharina, Grass, Karin, Oeckl, and Stephan, Kersting
- Subjects
Common Bile Duct ,Cholecystectomy, Laparoscopic ,Bile Ducts ,Biliary Tract ,Intraoperative Complications - Abstract
Laparoscopic cholecystectomy is one of the most frequently performed procedures worldwide. Therefore, iatrogenic injury to the choledochal duct, although rare, remains a surgical risk that should not be underestimated. Over the years, various methods have been described to avoid this serious complication, with its high morbidity and even mortality. One of the safest methods to avoid bile duct lesions is to establish the so called "critical view of safety" before cutting any structures. This method shall be demonstrated in this instructional video.Die laparoskopische Cholezystektomie ist eine der am häufigsten durchgeführten Operationen weltweit. Gerade aufgrund der hohen Fallzahlen bleibt die iatrogene Verletzung des Ductus choledochus, so selten sie ist, ein nicht zu unterschätzendes Risiko des Eingriffs. Im Laufe der Jahre wurden unterschiedliche Methoden beschrieben, diese schwerwiegende Komplikation mit ihrer hohen Morbidität und sogar Mortalität zu vermeiden. Eine der sichersten Methoden der Vermeidung von Gallengangsläsionen ist die Etablierung des sog. „critical view of safety“ vor Durchtrennung jeglicher Strukturen, der in diesem Lehrvideo demonstriert werden soll.
- Published
- 2020
47. Management of the left subclavian artery during TEVAR – complications and mid-term follow-up
- Author
-
Norbert Weiss, Ralf-Thorsten Hoffmann, Klaus Matschke, Akram Youssef, Stephan Kersting, Utz Kappert, Jennifer Lynne Leip, Adrian Mahlmann, and Tamer Ghazy
- Subjects
Male ,Reoperation ,Aortic arch ,medicine.medical_specialty ,Time Factors ,Computed Tomography Angiography ,medicine.medical_treatment ,Aortic Diseases ,Subclavian Artery ,Aorta, Thoracic ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,Revascularization ,Aortic repair ,Aortography ,Blood Vessel Prosthesis Implantation ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,Risk Factors ,medicine.artery ,medicine ,Humans ,030212 general & internal medicine ,Aged ,Retrospective Studies ,business.industry ,Endovascular Procedures ,Middle Aged ,Surgery ,Mid term follow up ,Treatment Outcome ,Descending aorta ,Left subclavian artery ,Female ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Abstract
Abstract. Background: Numerous conditions that affect the boundary between the aortic arch and descending aorta are treated with thoracic endovascular aortic repair (TEVAR). In 40 % of cases, coverage of the left subclavian artery (LSA) cannot be prevented. Subsequently, neurological complications such as stroke or ischemia of the left upper extremity may develop. However, the actual risk of these complications is subject to considerable controversy. The optimal treatment approach, specifically the question whether primary revascularization of the LSA should be performed in all cases, is unclear. Patients and methods: The present retrospective study analyzed the short- and mid-term results of patients treated with TEVAR with complete coverage of the LSA. The postoperative protocol consisted of clinical and noninvasive examinations as well as morphological imaging. Survival, complication, and reintervention rates were recorded. Results: A total of 40 patients, undergoing TEVAR with complete coverage of the LSA between January 2010 and December 2014 were analyzed retrospectively. The 30-day survival rate was 95 %, the survival one year after performed TEVAR was 67.5 %. The average follow-up was 1.5 years. After TEVAR procedure with complete coverage of the LSA, only one patient (2.5 %) developed critical ischemia of the left arm immediately after aortic stent implantation, requiring revascularization by transposition of the LSA. Anterior spinal artery syndrome occurred in another patient (2.5 %) immediately following TEVAR. During follow-up examinations, all patients showed a compensated arterial arm status. None of the patients developed new neurological deficits during the follow-up period. Conclusions: The study shows that performing TEVAR without primary revascularization of the LSA was justifiable in our cohort. An important risk factor of developing cerebral ischemia seems to be insufficient collateralization through the circle of Willis.
- Published
- 2018
- Full Text
- View/download PDF
48. Effect of Oxygenated Perfluorocarbons on Isolated Rat Pancreatic Islets in Culture
- Author
-
Hendrik Bergert M.D., Klaus-Peter Knoch, Ronny Meisterfeld, Melanie Jäger, Joke Ouwendijk, Stephan Kersting, Hans Detlev Saeger, and Michele Solimena
- Subjects
Medicine - Abstract
One impediment for a wider application of islet transplantation is the limited number of donor pancreata for islet isolation. A more efficient utilization of available organs could in part alleviate this problem. Perfluorocarbons (PFCs) have a high oxygen solubility coefficient and maintain high oxygen partial pressures for extended time. They serve also as oxygen “reservoirs” for harvested organs in pancreas organ transplantation. The aim of this study was to test whether the use of PFCs could also be beneficial for the secretory activity and overall viability of cultured purified islets before transplantation. Purified rat islets were cultured in static conditions with or without oxygen-saturated PFCs for 1 or 7 days. Cell death and apoptosis were assessed by trypan blue staining, DNA strand breaks, and caspase 3/7 activity. mRNA levels of insulin and ICA512/IA-2, a membrane marker of secretory granules (SGs), were quantitated by real-time PCR, whereas insulin content and secretion were measured by RIA. Polypyrimidine tract binding protein (PTB), which promotes SG biogenesis, was assessed by Western blotting. The number of SGs and the ultrastructural appearance of β-cells were analyzed by cryoimmunoelectronmicroscopy for insulin. Various parameters, including caspase activity, insulin and ICA512/IA-2 mRNA levels, PTB expression, number of secretory granules, and ultrastructural appearance did not significantly differ between control and PFC-cultured islets. On the other hand, PFC culture islets showed significantly increased DNA fragmentation and a reduced insulin stimulation index at both time points compared to control islets. While advantageous for the transport of human harvested organs, the use of PFH in the culture may be comparable to and/or not provide advantage over conventional protocols for culture of islets for transplantation.
- Published
- 2005
- Full Text
- View/download PDF
49. Intraduktale papillär-muzinöse Neoplasie des Seitengangs– Kontra Resektion
- Author
-
Stephan Kersting, Robert Grützmann, M Brunner, and Georg F. Weber
- Subjects
Gynecology ,03 medical and health sciences ,medicine.medical_specialty ,0302 clinical medicine ,Transplant surgery ,Cardiothoracic surgery ,business.industry ,030220 oncology & carcinogenesis ,medicine ,030211 gastroenterology & hepatology ,Surgery ,business ,Pancreatic surgery - Abstract
Die Diagnose intraduktaler papillar-muzinoser Neoplasien vom Seitengangtyp (Seitengang-IPMN) hat in den letzten Jahren durch eine Verbesserung der modernen bildgebenden Verfahren deutlich zugenommen. Seitengang-IPMN werden haufig als Zufallsbefunde bei asymptomatischen Patienten diagnostiziert. Das optimale Vorgehen beim Vorliegen einer Seitengang-IPMN ist Thema kontroverser Diskussionen. Zahlreiche Untersuchungen zeigen, dass eine individualisierte Therapiestrategie mit einer Verlaufsbeobachtung der meisten Seitengang-IPMN unter Berucksichtigung von Alter, Komorbiditaten und Patientenwunsch bevorzugt werden sollte. Grundlage hierfur bilden eine subtile Anamneseerhebung sowie eine genaue Diagnostik mit hochauflosenden bildgebenden Verfahren und endoskopischem Ultraschall. Symptomatische Patienten sowie Patienten mit sog. „high-risk stigmata“ sollten einer Resektion unterzogen werden. Asymptomatischen Patienten mit sog. „worrisome features“ kann entweder unter Berucksichtigung des Alters und der Komorbiditaten eine engmaschige Uberwachung oder eine chirurgische Resektion angeboten werden. Bei Seitengang-IPMN ohne „high-risk stigmata“ und „worrisome features“ sowie ohne Vorliegen einer Symptomatik ist eine Verlaufsbeobachtung das Vorgehen der Wahl. Vor allem die hohe Pravalenz von Seitengang-IPMN, Limitationen bei der Differenzialdiagnostik, ein uberschatztes Malignitatsrisiko aufgrund einer Uberreprasentation symptomatischer und suspekter Seitengang-IPMN in operierten Kohorten, eine uberschatzte Bedeutung von Seitengang-IPMN als Vorlauferlasionen fur das Pankreaskarzinom sowie der Nachweis der Sicherheit der Verlaufsbeobachtung unterstreichen den zunehmenden Stellenwert der Verlaufsbeobachtung. Basierend darauf und vor dem Hintergrund der nicht zu unterschatzenden Mortalitat und Morbiditat der Pankreaschirurgie ist ein aggressives Management mit prophylaktischer Resektion fur alle Seitengang-IPMN einschlieslich „risikoarmer“ Lasionen nicht gerechtfertigt.
- Published
- 2017
- Full Text
- View/download PDF
50. Outpatient Drainmanagement of patients with clinically relevant Postoperative Pancreatic Fistula (POPF)
- Author
-
Stephan Kersting, Marius Distler, Christoph Kahlert, Thilo Welsch, Jürgen Weitz, Sebastian Hempel, and Steffen Wolk
- Subjects
Adult ,Male ,medicine.medical_specialty ,Percutaneous ,Pancreatic Fistula ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,Risk Factors ,Ambulatory Care ,medicine ,Humans ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Pancreatic Diseases ,Length of Stay ,Middle Aged ,Vascular surgery ,medicine.disease ,Cardiac surgery ,Surgery ,Pancreatic fistula ,Cardiothoracic surgery ,030220 oncology & carcinogenesis ,Ambulatory ,Quality of Life ,Drainage ,Female ,030211 gastroenterology & hepatology ,Complication ,business ,Abdominal surgery - Abstract
Postoperative pancreatic fistula (POPF) is a common complication after pancreatic surgery associated with extended hospitalization, increased medical costs, and reduced quality of life. The aim of the present study was to analyze the feasibility of ambulatory drainage and develop an ambulatory management algorithm. Patients with POPF grade B or C (according to the ISGPF classification) between Jan. 2005 and Dec. 2014 that required persistent drainage were identified from a prospectively collected database. Postoperative events and clinical outcomes were retrospectively analyzed. A total of 132 out of 887 patients (14.8%) developed a POPF (grade B or C), and 45 (34.1%) were discharged from the hospital with percutaneous drainage. For patients with grade B fistulas, the mean hospital stay was significantly shorter compared to patients with grade C fistulas (mean 27.7 vs. 40 days; p = 0.0285). About 40% of patients with ambulatory drainage developed a complication, but only 28.9% required readmission. Of those, 52.9% did not require specific treatment and 26.3% were treated with a new drain placement. None of the patients developed major complications, and there was no difference in the frequency of complications between the two groups (p = 0.872). The duration of drain persistence was significantly shorter for patients with grade B fistulas than for those with grade C fistulas (52.2 vs. 85.9 days; p = 0.0007). Ambulatory drainage management is feasible in selected patients. No severe complications occurred during ambulatory drainage management. A management algorithm is recommended as this could possibly reduce medical costs and improve quality of life.
- Published
- 2017
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.