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result(s) for
"Seyfried, Steffen"
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Myeloid-derived suppressor cells in peripheral blood as predictive biomarkers in patients with solid tumors undergoing immune checkpoint therapy: systematic review and meta-analysis
by
Hetjens, Svetlana
,
Reißfelder, Christoph
,
Hardt, Julia
in
Bias
,
Biomarkers
,
Biomarkers, Tumor - blood
2024
Immunotherapeutic approaches, including immune checkpoint inhibitor (ICI) therapy, are increasingly recognized for their potential. Despite notable successes, patient responses to these treatments vary significantly. The absence of reliable predictive and prognostic biomarkers hampers the ability to foresee outcomes. This meta-analysis aims to evaluate the predictive significance of circulating myeloid-derived suppressor cells (MDSC) in patients with solid tumors undergoing ICI therapy, focusing on progression-free survival (PFS) and overall survival (OS).
A comprehensive literature search was performed across PubMed and EMBASE from January 2007 to November 2023, utilizing keywords related to MDSC and ICI. We extracted hazard ratios (HRs) and 95% confidence intervals (CIs) directly from the publications or calculated them based on the reported data. A hazard ratio greater than 1 indicated a beneficial effect of low MDSC levels. We assessed heterogeneity and effect size through subgroup analyses.
Our search yielded 4,023 articles, of which 17 studies involving 1,035 patients were included. The analysis revealed that patients with lower levels of circulating MDSC experienced significantly improved OS (HR=2.13 [95% CI 1.51-2.99]) and PFS (HR=1.87 [95% CI 1.29-2.72]) in response to ICI therapy. Notably, heterogeneity across these outcomes was primarily attributed to differences in polymorphonuclear MDSC (PMN-MDSC) subpopulations and varying cutoff methodologies used in the studies. The monocytic MDSC (M-MDSC) subpopulation emerged as a consistent and significant prognostic marker across various subgroup analyses, including ethnicity, tumor type, ICI target, sample size, and cutoff methodology.
Our findings suggest that standardized assessment of MDSC, particularly M-MDSC, should be integral to ICI therapy strategies. These cells hold the promise of identifying patients at risk of poor response to ICI therapy, enabling tailored treatment approaches. Further research focusing on the standardization of markers and validation of cutoff methods is crucial for integrating MDSC into clinical practice.
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023420095, identifier CRD42023420095.
Journal Article
Less is more—the best test for anastomotic leaks in rectal cancer patients prior to ileostomy reversal
by
Reissfelder, Christoph
,
Hetjens, Svetlana
,
Hardt, Julia
in
Anastomosis
,
Anastomosis, Surgical - adverse effects
,
Anastomotic leak
2021
Purpose
No clear consensus exists on how to routinely assess the integrity of the colorectal anastomosis prior to ileostomy reversal. The objective of this study was to evaluate the accuracy of contrast enema, endoscopic procedures, and digital rectal examination in rectal cancer patients in this setting.
Methods
A systematic literature search was performed. Studies assessing at least one index test for which a 2 × 2 table was calculable were included. Hierarchical summary receiver operating characteristic curves were calculated and used for test comparison. Paired data were used where parameters could not be calculated. Methodological quality was assessed with the QUADAS-2 tool.
Results
Two prospective and 11 retrospective studies comprising 1903 patients were eligible for inclusion. Paired data analysis showed equal or better results for sensitivity and specificity of both endoscopic procedures and digital rectal examination compared to contrast enema. Subgroup analysis of contrast enema according to methodological quality revealed that studies with higher methodological quality reported poorer sensitivity for equal specificity and vice versa. No case was described where a contrast enema revealed an anastomotic leak that was overseen in digital rectal examination or endoscopic procedures.
Conclusions
Endoscopy and digital rectal examination appear to be the best diagnostic tests to assess the integrity of the colorectal anastomosis prior to ileostomy reversal. Accuracy measures of contrast enema are overestimated by studies with lower methodological quality. Synopsis of existing evidence and risk–benefit considerations justifies omission of contrast enema in favor of endoscopic and clinical assessment.
Trial registration
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019107771
Journal Article
Newly established gastrointestinal cancer cell lines retain the genomic and immunophenotypic landscape of their parental cancers
2020
Human cancer cell lines are frequently used as model systems to study molecular mechanisms and genetic changes in cancer. However, the model is repeatedly criticized for its lack of proximity to original patient tumors. Therefore, understanding to what extent cell lines cultured under artificial conditions reflect the phenotypic and genomic profiles of their corresponding parental tumors is crucial when analyzing their biological properties. To directly compare molecular alterations between patient tumors and derived cell lines, we have established new cancer cell lines from four patients with gastrointestinal tumors. Tumor entities comprised esophageal cancer, colon cancer, rectal cancer and pancreatic cancer. Phenotype and genotype of both patient tumors and derived low-passage cell lines were characterized by immunohistochemistry (22 different antibodies), array-based comparative genomic hybridization and targeted next generation sequencing (48-gene panel). The immunophenotype was highly consistent between patient tumors and derived cell lines; the expression of most markers in cell lines was concordant with the respective parental tumor and characteristic for the respective tumor entities in general. The chromosomal aberration patterns of the parental tumors were largely maintained in the cell lines and the distribution of gains and losses was typical for the respective cancer entity, despite a few distinct differences. Cancer gene mutations (e.g.,
KRAS
,
TP53
) and microsatellite status were also preserved in the respective cell line derivates. In conclusion, the four examined newly established cell lines exhibited a phenotype and genotype closely recapitulating their parental tumor. Hence, newly established cancer cell lines may be useful models for further pharmacogenomic studies.
Journal Article
Correction to: Trocar Site Hernias in Bariatric Surgery—an Underestimated Issue: a Qualitative Systematic Review and Meta-Analysis
2020
The review was not registered for systematic reviews and meta-analyses, and should be disregarded.
Journal Article
Enteral resorbable diet versus standard diet in primary sphincter reconstruction: a prospective randomised trial
by
Joos, Andreas
,
Galata, Christian
,
Reißfelder, Christoph
in
Analysis
,
Anorectal
,
Clinical trials
2021
Aim
Bowel movements after reconstructive anorectal surgery may negatively affect surgical outcome. This study was aimed to assess any differences between a standard diet (SD) and the enteral resorbable diet (ED) in terms of operative outcomes and patient tolerance after fistulectomy with primary sphincter reconstruction.
Method
Adult patients undergoing elective fistulectomy with primary sphincter reconstruction for anorectal and rectovaginal fistulas were eligible for inclusion. Patients were intraoperatively randomised to receive either the ED and peristalsis-inhibiting medication (ED) or a SD. The primary endpoint was the healing rate. Secondary endpoints included continence scores, complications and quality of life. Sample size calculation resulted in the analysis of 60 patients to detect a difference in fistula recurrence of 30% with 70% power and a 5% significance level.
Results
Sixty-six patients (24 women) were prospectively and randomly assigned to the ED (
n
= 34: 51%) or a SD (
n
= 32; 48%); mean age was 47 (18-74) years. The primary healing rate was 64 out of 66 patients (96%). No statistical difference in healing rate was seen between the groups. However, patient satisfaction was significantly higher in the SD group (
P
< 0.0001).
Conclusions
Fistulectomy with primary sphincter reconstruction is a safe method with low complication rates. Postoperative stool behaviour has no significant influence on the healing rate but has a significant negative impact on patient satisfaction. Therefore, maintaining a standard diet seems to be preferable following reconstructive anal surgery.
Trial registration
The trial was registered with the German Clinical Trials Register (
DRKS00020524
).
Journal Article
Prähabilitation abseits spezialisierter Zentren
2025
Die Prähabilitation gewinnt zunehmend an Bedeutung als integraler Bestandteil des perioperativen Managements. Sie verbessert funktionelle Reserven vor chirurgischen Eingriffen und reduziert postoperative Komplikationen. Während spezialisierte Zentren erfolgreich Prähabilitationsprogramme implementieren, bleibt die flächendeckende Umsetzung, insbesondere in ländlichen Regionen, eine Herausforderung. Organisatorische, infrastrukturelle und finanzielle Hürden erschweren die Adaption außerhalb universitärer Einrichtungen. Digitale und hybride Ansätze bieten jedoch Potenzial, um eine wohnortnahe Versorgung zu ermöglichen. Eine nachhaltige Integration in das Gesundheitssystem erfordert sektorenübergreifende Kooperationen, politische Unterstützung und angepasste Vergütungsstrukturen.
Journal Article
Weiterhin keine Evidenz für Drainagen in der Bariatrie
2020
HintergrundRegisterdaten zeigen, dass eine Drainageneinlage im Rahmen bariatrischer Operationen immer noch gängige Praxis in vielen chirurgischen Abteilungen ist. Retrospektive Studien und eine Übersichtsarbeit konnten zeigen, dass die routinemäßige Einlage einer Drainage im Rahmen bariatrischer Operationen nutzlos und potenziell auch gefährdend ist. In der Literatur konnte aufgrund fehlender randomisierter kontrollierter Studien keine ausreichende Evidenz zu diesem Thema geschaffen werden.ZielUm den Nutzen von Drainagen bei bariatrischen Eingriffen weiter zu hinterfragen, haben wir unsere prospektiv erhobene Datenbank von Patienten, die zwischen Januar 2010 und Juni 2016 eine Schlauchmagenanlage (SG) oder einen Roux-en-Y-Magenbypass (RYGB) erhielten, retrospektiv ausgewertet.SettingDeutsches UniversitätsklinikumMethodenWährend des Untersuchungszeitraums wurden insgesamt 361 Operationen (219 Magenbypass- und 142 Schlauchmagenoperationen) durchgeführt. Eine Änderung unseres internen Behandlungspfades in Bezug auf die Platzierung von Drainagen im Jahr 2013 führte dabei zu zwei Gruppen: eine, bei der routinemäßig Drainagen bei Operationen platziert wurden (166), und eine bei denen keine Drainage angelegt wurde (195). Die demografischen Daten wurden mithilfe multipler Regressionsanalyse statistisch zwischen den beiden Gruppen adjustiert. Wir verglichen die Operationsergebnisse und die 30-Tage-Morbidität. Komplikationen wurden nach der Clavien-Dindo-Klassifikation bewertet.ErgebnisseIn der Gruppe ohne Drainage hatten 7 Patienten Komplikationen. In der Drainagegruppe traten 6 Komplikationen auf. Die Insuffizienzraten und Reoperationsraten zwischen den Gruppen waren statistisch nicht unterschiedlich. Im Durchschnitt wurde der postoperative Aufenthalt bei Patienten mit Drainage um 1,3 Tage verlängert. Die multivariate Analyse zeigte, dass die Platzierung von Drainagen der höchste Risikofaktor für einen längeren Krankenhausaufenthalt ist.SchlussfolgerungDrainagenanlagen im Rahmen bariatrischer Eingriffe sollten eine individuelle Überlegung sein. Von der routinemäßigen Verwendung sollte abgeraten werden.
Journal Article
Robotic or laparoscopic repeat hepatectomy after open hepatectomy: a cohort study
by
Téoule, Patrick
,
Reißfelder, Christoph
,
Rahbari, Nuh N
in
Clinical trials
,
Cohort analysis
,
Endoscopy
2024
BackgroundRepeat hepatectomies are technically complex procedures. The evidence of robotic or laparoscopic (= minimally invasive) repeat hepatectomies (MIRH) after previous open hepatectomy is poor. Therefore, we compared postoperative outcomes of MIRH vs open repeat hepatectomies (ORH) in patients with liver tumors after previous open liver resections.MethodsConsecutive patients who underwent repeat hepatectomies after open liver resections were identified from a prospective database between April 2018 and May 2023. Postoperative complications were graded in line with the Clavien-Dindo classification. We stratified patients by intention to treat into MIRH or ORH and compared outcomes. Logistic regression analysis was performed to define variables associated with the utilization of a minimally invasive approach.ResultsAmong 46 patients included, 20 (43%) underwent MIRH and 26 (57%) ORH. Twenty-seven patients had advanced or expert repeat hepatectomies (59%) according to the IWATE criteria. Baseline characteristics were comparable between the study groups. The use of a minimally invasive approach was not dependent on preoperative or intraoperative variables. All patients had negative resection margins on final histology. MIRH was associated with less blood loss (450 ml, IQR (interquartile range): 200–600 vs 600 ml, IQR: 400–1500 ml, P = 0.032), and shorter length of stay (5 days, IQR: 4–7 vs 7 days, IQR: 5–9 days, P = 0.041). Postoperative complications were similar between the groups (P = 0.298).ConclusionsMIRH is feasible after previous open hepatectomy and a safe alternative approach to ORH.(German Clinical Trials Register ID: DRKS00032183)
Journal Article
Trocar Site Hernias in Bariatric Surgery—an Underestimated Issue: a Qualitative Systematic Review and Meta-Analysis
by
Weiss, Christel
,
Hetjens, Svetlana
,
Vassilev, Georgi
in
Gastrointestinal surgery
,
Hernias
,
Meta-analysis
2019
The reported incidence of trocar site hernias in bariatric surgery ranges between 0.5 and 3%. The best available evidence derives from retrospective studies analysing prospective databases, thus including only patients who presented with symptoms or received surgical treatment due to trocar site hernias after a laparoscopic bariatric procedure. A systematic literature research was conducted up until September 2017. Search strategies included proper combinations of the MeSH terms ‘laparoscopy’ and ‘bariatric surgery’, ‘trocar/port’ and ‘hernia’. Searches were not limited by publication type or language. The review was registered in PROSPERO (ID 85102) and performed according to the PRISMA guidelines. Sixty-eight publications were included. Pooled hernia incidence was 3.22 (range 0–39.3%). Thirteen trials reported systematic closure of the fascia; 12 trials reported no closure. Data availability did not allow for pooling to calculate relative risk. Higher BMI and specific hernia examination using imaging modalities were associated with a significantly higher incidence of trocar site hernias. Studies dedicated to detection of TsH reported a pooled incidence of 24.5%. Trocar site hernias are an underestimated complication of minimally invasive multiportal bariatric surgery. While high-quality trials are not available allowing for a precise calculation of the incidence, existing data are indicative of very high incidence rates. Risk factors for developing a trocar site hernia in bariatric surgery have not yet been systematically analysed. Prospective studies in this field are necessary.
Journal Article
Reconstruction of the perineal defect after abdominoperineal resection with vertical rectus abdominis myocutaneous (VRAM) flap versus primary direct closure - a single center retrospective cohort study
2025
Purpose
The closure of the perineal defect following pelvic surgery that includes abdomino-perineal resection (APR) can often be challenging and remains an important issue given the reported high wound morbidity. The vertical rectus abdominis myocutaneous (VRAM) flap, which was proposed in the past as an alternative to direct closure (DC), enables the reconstruction of extensive perineal wounds.
Methods
184 consecutive patients who underwent abdominoperineal resection at tertiary university institution between January 2014 and June 2024 were included in this retrospective analysis. The aim of the study was to evaluate the outcomes of perineal wound reconstruction using a VRAM flap (
n
= 29) compared to DC (
n
= 155).
Results
The rate of overall perineal and abdominal wall wound complications did not differ significantly (
p
= 0.321 and
p
= 1.000, respectively). However, significantly more pelvic abscesses requiring CT-guided percutaneous drainage were observed in the DC-group (
p
= 0.048). Subgroup analysis of patients who underwent radiochemotherapy prior to surgery revealed lower incidence of severe perineal complications after VRAM flap reconstruction of the perineal defect (
p
= 0.037).
Conclusion
The VRAM flap has proven to be a safe technique and should be considered especially for the reconstruction of extensive perineal defects following pelvic surgery.
Journal Article