Onset Time and Characteristics of Postprocedural Bleeding after Endoscopic Resection of Colorectal Lesions: A Multicenter Retrospective Study.

INTRODUCTION: Postprocedural bleeding is a major adverse event after endoscopic resection of colorectal lesions, but the optimal surveillance time after endoscopy is unclear. In this study, we determined onset time and characteristics of postprocedural bleeding events. METHODS: We retrospectively screened patients who underwent endoscopic resection of colorectal lesions at three German hospitals between 2010 and 2019 for postprocedural bleeding events using billing codes. Only patients who required re-endoscopy were included for analysis. For identified patients, we collected demographic data, clinical courses, characteristics of colorectal lesions, and procedure-related variables. Factors associated with late-onset bleeding were determined by univariate and multivariate logistic regression analysis. RESULTS: From a total of 6,820 patients with eligible billing codes, we identified 113 cases with postprocedural bleeding after endoscopic mucosal (61.9%) or snare resection (38.1%) that required re-endoscopy. The median size of the culprit lesion was 20 mm (interquartile range 14-30 mm). The median onset time of postprocedural bleeding was day 3 (interquartile range: 1-6.5 days), with 48.7% of events occurring within 48 h. Multivariate logistic regression analysis demonstrates that a continued intake of antiplatelet drugs (OR: 3.98, 95% CI: 0.89-10.12, p = 0.025) and a flat morphology of the colorectal lesion (OR: 2.98, 95% CI: 1.08-8.01, p = 0.031) were associated with an increased risk for late postprocedural bleeding (>48 h), whereas intraprocedural bleeding was associated with a decreased risk (OR: 0.12, 95% CI: 0.04-0.50, p = 0.001). CONCLUSION: Significant postprocedural bleeding can occur up to 18 days after endoscopic resection of colorectal lesions, but was predominantly observed within 48 h. Continued intake of antiplatelet drugs and a flat polyp morphology are associated with risk for late postprocedural bleeding.

The role of the multidisciplinary tumor board after endoscopic resection of malignant tumors: is it worth it?

OBJECTIVES: The value of multidisciplinary tumor boards (MTBs) in the treatment of gastrointestinal cancer patients is well known. Most of the current evidence focuses on advanced cancer cases, whereas little is known about the effect of MTBs on early tumors, especially after endoscopic resection. The aim of our study is to evaluate the value of the MTB after endoscopic resection of malignant tumors of the gastrointestinal tract. METHODS: We retrospectively analyzed all endoscopically resected malignant tumors in our department between 2011 and 2019, focusing on the existence of an MDT recommendation after endoscopic resection, the MDT adherence to the current guidelines, and the implementation of the recommendation by the patients. RESULTS: We identified 198 patients fulfilling our inclusion criteria, of whom 168 (85%) were discussed in the MDT after endoscopic resection. In total, 155 of the recommendations (92%) were in accordance with the current guidelines, and 147 (88%) of them were implemented by the patients. The MDT discussion itself did not influence the overall survival, whereas the implementation of the MTB recommendation was associated with a significantly better prognosis. Deviations of the MDT recommendation from the guidelines had no effect on the overall survival. CONCLUSIONS: The discussion of endoscopically resected malignant tumors in the MTB is crucial for the treatment of patients with this type of cancer, since the implementation of the MTB recommendation, even if it deviates from the current guidelines, improves the prognosis.

Endoscopic submucosal dissection versus endoscopic mucosal resection for the treatment of rectal lesions involving the dentate line.

BACKGROUND: The ideal treatment of epithelial neoplastic rectal lesions involving the dentate line is a controversial issue. Piecemeal endoscopic mucosal resection (EMR) is the most commonly used resection technique, but it is associated with high recurrence rates. Endoscopic submucosal dissection (ESD) has been shown to be safe and effective for the treatment of rectal lesions, but evidence is lacking concerning its application close to the dentate line. The aim of our study is to compare ESD and EMR for the treatment of epithelial rectal lesions involving the dentate line. METHODS: We identified all cases of endoscopic resections of rectal lesions involving the dentate line performed in two German high-volume centers between 2010 and 2022. Periinterventional and follow-up data were collected and retrospectively analyzed. RESULTS: We identified 68 ESDs and 62 EMRs meeting our inclusion criteria. ESD showed a significant advantage in en bloc resection rates (89.7% vs. 9.7%; P = 0.001) and complete resection rates (72.1% vs. 9.7%; P = 0.001). The overall curative resection rate was similar between both groups (ESD: 92.6%, EMR: 83.9%; P = 0.324), whereas in the subgroup of low-risk adenocarcinomas ESD was curative in 100% of the cases vs. 14% in the EMR group (P = 0.002). There was one local recurrence after ESD (1,5%) vs. 16 (25.8%) after EMR (P < 0.0001), and the EMR patients required an average of three further interventions. CONCLUSION: ESD is superior to EMR for the treatment of epithelial rectal lesions involving the dentate line and should be considered the treatment of choice.

[Impact Analysis of a new, Cross-sector Service Provision of Gastroenterologic Endoscopic Services in Accordance with 115f SGB V (Hybrid-DRG): Allocation Matrix and Cost Analysis]. / Auswirkungsanalyse einer neuen, sektorenübergreifenden Erbringung bisher stationärer endoskopischer gastroenterologischer Leistungen entsprechend §115f SGB V (Hybrid-DRG): Zuordnungsmatrix und Kostenanalyse.

BACKGROUND: With the introduction of §115f SGB V, the prerequisites for "sector-equal remuneration" ('Hybrid DRG') have been created. In an impact analysis, we assigned inpatient gastroenterological endoscopic (GAEN) cases in a matrix of future hybrid DRG versus outpatient surgery (AOP) or inpatient treatment. METHODS: In selected DRGs (G47B, G67A, G67B, G67C, G71Z, H41D, H41E) an allocation matrix of GAEN cases was created on medical grounds. For this purpose, service groups from the DGVS service catalog ('Leistungskatalog') were assigned to the groups: 'Hybrid-DRG', 'AOP' and 'Inpatient' by a group of experts based on the DGVS position paper. Cost data from the DGVS-DRG project for the 2022 data year from 36 InEK calculation hospitals with a total of 232,476 GAEN cases were evaluated. RESULTS: 26 service groups from the DGVS service catalog were assigned to a "Hybrid-DRG", 24 to the "inpatient" group, and 12 to the "AOP" group. 7 performance groups were splitted "depending on the OPS code" and classified at this level. Cases with additional fees were excluded from a hybrid DRG because these cannot be agreed there.The cost analysis shows that services that are already in the AOP have a similar cost level to services that have been classified as 'Hybrid-DRG'. With the cost calculation, a cost level could be presented for the hybrid DRGs formed. CONCLUSION: Based on clearly defined structural, procedural and personnel requirements, services from suitable DRGs can be transferred to a hybrid DRG. Assigning services without the involvement of clinical experts seems extremely difficult. Case assignment based on arbitrary contextual factors increases complexity without demonstrably increasing the quality of the assignment and needs to be further developed. A cost analysis can be derived from the known inpatient costs and must serve as the basis for the 2025 Hybrid DRG catalog.

Colonic Wall Injuries After Endoscopic Resection: Still a Major Complication? A Retrospective Analysis of 3782 Endoscopic Resections.

BACKGROUND: Colonic wall injuries are the most feared adverse events of endoscopic resections among endoscopists. The implementation of endoscopic closure has offered a reliable way to treat such injuries and, thus, has decreased their overall morbidity and mortality. OBJECTIVES: The aim of our study is to assess the characteristics and outcomes of colonic wall injuries after endoscopic resection, focusing on the endoscopic treatment of these injuries. DESIGN: This was a retrospective cohort study. SETTINGS: Patients treated in the Central Endoscopy Unit of the Medical Centre Mannheim were included. PATIENTS: We retrospectively analyzed all patients who underwent endoscopic mucosal resection and snare polypectomy in our center between 2004 and 2019 and isolated the resection-related colonic wall injuries. These were divided into 3 groups: group A, endoscopically treated early colonic wall injuries; group B, nonendoscopically treated early colonic wall injuries; and group C, late perforations. MAIN OUTCOME MEASURES: Periprocedural factors and treatment outcomes were analyzed and compared among the 3 groups. RESULTS: Of 3782 endoscopic resections, we identified 177 cases of colonic wall injuries, of which 148 were identified and treated endoscopically (group A), 9 were identified during the procedure but could not be treated endoscopically (group B), and 20 were late perforations (group C). Endoscopic treatment with use of clips had a technical success rate of 94.3%, while the clinical success rate of technically complete endoscopic closure was 92.6%. Twenty-two percent of all colonic wall injuries required surgical treatment; the type and outcomes of surgery were similar in all groups. Overall hospital stay was significantly lower in group A. LIMITATIONS: The main limitation of the study is its retrospective design. CONCLUSIONS: Endoscopic closure with the use of clips is a safe and feasible treatment for intraprocedurally identified colonic wall injuries and is associated with significantly decreased necessity of surgery, morbidity, and hospital stay. See Video Abstract at http://links.lww.com/DCR/B755. LESIONES DE PARED COLNICA POSTERIOR A RESECCIN ENDOSCPICA ES AN UNA COMPLICACIN IMPORTANTE ANLISIS RETROSPECTIVO DE RESECCIONES ENDOSCPICAS: ANTECEDENTES:Las lesiones de la pared del colon son los eventos adversos más temidos por los endoscopistas durante las resecciones endoscópicas. La implementación del cierre endoscópico ha ofrecido una forma confiable de tratar tales lesiones y, por lo tanto, disminuyendo su morbilidad y mortalidad general.OBJETIVOS:El objetivo de nuestro estudio es evaluar las características y resultados de las lesiones de la pared colónica posterior a la resección endoscópica, centrándose en su tratamiento endoscópico.DISEÑO:Es un estudio de cohorte retrospectivo.ENTORNO CLÍNICO:Se incluyeron pacientes tratados en la Unidad Central de Endoscopia del Centro Médico de Mannheim.PACIENTES:Se analizaron retrospectivamente todos los pacientes sometidos a resección endoscópica de la mucosa y polipectomía en asa en nuestro centro entre 2004 y 2019, seleccionando las lesiones de la pared colónica relacionadas a la resección. Estas se dividieron en tres grupos: Grupo A: lesiones tempranas de la pared colónica tratadas endoscópicamente; Grupo B: lesiones tempranas de la pared colónica no tratadas endoscópicamente; y Grupo C: perforaciones tardías.PRINCIPALES MEDIDAS DE VALORACION:Se analizaron y compararon los factores relacionados al procedimiento y los resultados del tratamiento entre los tres grupos.RESULTADOS:De 3782 resecciones endoscópicas identificamos 177 casos de lesiones de la pared colónica, de los cuales 148 fueron identificados y tratados endoscópicamente (Grupo A), 9 fueron identificados durante el procedimiento pero no pudieron ser tratados endoscópicamente (Grupo B) y 20 fueron perforaciones tardías. (Grupo C). El tratamiento endoscópico con el uso de clips tuvo una tasa de éxito técnico del 94,3%, mientras que la tasa de éxito clínico del cierre endoscópico técnicamente completo fue del 92,6%. El veintidós por ciento de todas las lesiones de la pared colónica requirieron tratamiento quirúrgico; el tipo y los resultados de la cirugía fueron los mismos en todos los grupos. La estancia hospitalaria global fue significativamente menor en el grupo A.LIMITACIONES:La principal limitación del estudio es su diseño retrospectivo.CONCLUSIONES:El cierre endoscópico con el uso de clips es un tratamiento seguro y factible para las lesiones de la pared colónica identificadas durante el procedimiento y se asocia con una disminución significativa de la necesidad de cirugía, morbilidad y de estancia hospitalaria. Consulte Video Resumen en http://links.lww.com/DCR/B755.

Endoscopic papillectomy or pancreaticoduodenectomy for ampullary lesions: a single center retrospective cohort study.

BACKGROUND: This study aimed to compare post-operative morbidity, mortality, and completeness of resection following endoscopic vs. radical surgical resection for ampullary lesions. METHODS: A retrospective analysis of the prospectively collected data from a surgical database for patients with ampullary lesions at our institution was performed. All consecutive patients undergoing endoscopic papillectomy (EP) or pancreaticoduodenectomy (PD) for ampullary lesions between 2007 and 2021 were eligible for this analysis. RESULTS: A total of 85 patients were included of whom 42 underwent EP whereas 43 received a PD. The resected lesion was a tubulovillous adenoma in 26 patients (61.9%) in the EP cohort, and 37 patients (86.0%) in the PD cohort had adenocarcinomas. The completeness of resection was equal in both cohorts. Significantly more patients of the PD cohort had to undergo reinterventions. After a mean follow up of 36 months (EP) vs. 16 months (PD), the rate of tumor recurrence did not differ between both groups. CONCLUSION: Equivalently high completeness of resection rates and correspondingly low recurrence rates can be achieved after EP and PD. Our results regarding residual tumor and recurrence rates show that even large tumors can be resected endoscopically with high primary success and completeness of resection rates.

Proposal of an algorithm for the management of rectally inserted foreign bodies: a surgical single-center experience with review of the literature.

BACKGROUND: Retained rectal foreign bodies (RFBs) are uncommon clinical findings. Although the management of RFBs is rarely reported in the literature, clinicians regularly face this issue. To date, there is no standardized management of RFBs. The aim of the present study was to evaluate our own data and subsequently develop a treatment algorithm. METHODS: All consecutive patients who presented between January 2006 and December 2019 with rectally inserted RFBs at the emergency department of the Klinikum Stuttgart, Germany, were retrospectively identified. Clinicopathologic features, management, complications, and outcomes were assessed. Based on this experience, a treatment algorithm was developed. RESULTS: A total of 69 presentations with rectally inserted RFBs were documented in 57 patients. In 23/69 cases (33.3%), the RFB was removed transanally by the emergency physician either digitally (n = 14) or with the help of a rigid rectoscope (n = 8) or a colonoscope (n = 1). In 46/69 cases (66.7%), the RFB was removed in the operation theater under general anesthesia with muscle relaxation. Among these, 11/46 patients (23.9%) underwent abdominal surgery, either for manual extraction of the RFB (n = 9) or to exclude a bowel perforation (n = 2). Surgical complications occurred in 3/11 patients. One patient with rectal perforation developed pelvic sepsis and underwent abdominoperineal extirpation in the further clinical course. CONCLUSION: The management of RFBs can be challenging and includes a wide range of options from removal without further intervention to abdominoperineal extirpation in cases of pelvic sepsis. Whenever possible, RFBs should obligatorily be managed in specialized colorectal centers following a clear treatment algorithm.

[Management of Endoscopic Complications after Bariatric Surgery: Focus on Current Endoscopic Therapy]. / Endoskopisches Komplikationsmanagment nach bariatrischen Operationen mit dem Fokus auf die aktuellen endoskopischen Therapien.

In bariatric surgery, complications are rare. Most of the complications can be managed by endoscopy. Rare complications impose a challenge in everyday clinical work. To optimally treat the complications and to minimise the harm to the patient it is important to implement complication management. This review gives an overview of relevant bariatric complications and endoscopic therapy strategies, focusing on published literature of the last five years. This manuscript could be a starting point for complication management in the clinic.

Endoscopic negative pressure therapy for leaks with large cavities in the upper gastrointestinal tract: is it a feasible therapeutic option?

BACKGROUND: Endoscopic negative pressure therapy (ENPT) is an increasingly popular method for the treatment of various defects of the upper and lower gastrointestinal (GI) tract and has been associated with high success rates. The largest reported series focus on intraluminal therapy of local defects, whereas larger defects connected to the abdominal or pleural cavity are still regarded as indications for surgical revision in many units. The aim of our study is to assess the efficacy and the periinterventional characteristics of ENPT applications in patients with defects with large cavities in the upper GI tract. METHODS: We retrospectively analysed all cases of ENPT applications in the upper gastrointestinal tract performed in our clinic between 1 January 2010 and 31 December 2019 and identified the patients with defects leading to large cavities with a length of at least 7 cm. The procedural characteristics, intraprocedural and late complications and overall clinical success were analysed. RESULTS: We identified 14 cases meeting our inclusion criteria. In all cases, an intracavitary or combined intracavitary and intraluminal ENPT was applied. The average duration of therapy was 47.5 days and included an average of 10.4 changes per patient in an interval of 4.5 days. Clinical success rate was 92.9%, average hospital stay was 74.5 days. In three cases, a late stenosis occurred, which could be treated endoscopically. CONCLUSION: Based on the data of our case series, we conclude that ENPT is a feasible and promising therapeutic option for upper GI defects with contact to large cavities.

Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial.

BACKGROUND: Docetaxel-based chemotherapy is effective in metastatic gastric and gastro-oesophageal junction adenocarcinoma. This study reports on the safety and efficacy of the docetaxel-based triplet FLOT (fluorouracil plus leucovorin, oxaliplatin and docetaxel) as a perioperative therapy for patients with locally advanced, resectable tumours. METHODS: In this controlled, open-label, phase 2/3 trial, we randomly assigned 716 patients with histologically-confirmed advanced clinical stage cT2 or higher or nodal positive stage (cN+), or both, resectable tumours, with no evidence of distant metastases, via central interactive web-based-response system, to receive either three pre-operative and three postoperative 3-week cycles of 50 mg/m2 epirubicin and 60 mg/m2 cisplatin on day 1 plus either 200 mg/m2 fluorouracil as continuous intravenous infusion or 1250 mg/m2 capecitabine orally on days 1 to 21 (ECF/ECX; control group) or four preoperative and four postoperative 2-week cycles of 50 mg/m2 docetaxel, 85 mg/m2 oxaliplatin, 200 mg/m2 leucovorin and 2600 mg/m2 fluorouracil as 24-h infusion on day 1 (FLOT; experimental group). The primary outcome of the trial was overall survival (superiority) analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01216644. FINDINGS: Between Aug 8, 2010, and Feb 10, 2015, 716 patients were randomly assigned to treatment in 38 German hospitals or with practice-based oncologists. 360 patients were assigned to ECF/ECX and 356 patients to FLOT. Overall survival was increased in the FLOT group compared with the ECF/ECX group (hazard ratio [HR] 0·77; 95% confidence interval [CI; 0.63 to 0·94]; median overall survival, 50 months [38·33 to not reached] vs 35 months [27·35 to 46·26]). The number of patients with related serious adverse events (including those occurring during hospital stay for surgery) was similar in the two groups (96 [27%] in the ECF/ECX group vs 97 [27%] in the FLOT group), as was the number of toxic deaths (two [<1%] in both groups). Hospitalisation for toxicity occurred in 94 patients (26%) in the ECF/ECX group and 89 patients (25%) in the FLOT group. INTERPRETATION: In locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma, perioperative FLOT improved overall survival compared with perioperative ECF/ECX. FUNDING: The German Cancer Aid (Deutsche Krebshilfe), Sanofi-Aventis, Chugai, and Stiftung Leben mit Krebs Foundation.

Genome-wide DNA methylation analysis of colorectal adenomas with and without recurrence reveals an association between cytosine-phosphate-guanine methylation and histological subtypes.

Aberrant methylation of DNA is supposed to be a major and early driver of colonic adenoma development, which may result in colorectal cancer (CRC). Although gene methylation assays are used already for CRC screening, differential epigenetic alterations of recurring and nonrecurring colorectal adenomas have yet not been systematically investigated. Here, we collected a sample set of formalin-fixed paraffin-embedded colorectal low-grade adenomas (n = 72) consisting of primary adenomas without and with recurrence (n = 59), recurrent adenomas (n = 10), and normal mucosa specimens (n = 3). We aimed to unveil differentially methylated CpG positions (DMPs) across the methylome comparing not only primary adenomas without recurrence vs primary adenomas with recurrence but also primary adenomas vs recurrent adenomas using the Illumina Human Methylation 450K BeadChip array. Unsupervised hierarchical clustering exhibited a significant association of methylation patterns with histological adenoma subtypes. No significant DMPs were identified comparing primary adenomas with and without recurrence. Despite that, a total of 5094 DMPs (false discovery rate <0.05; fold change >10%) were identified in the comparisons of recurrent adenomas vs primary adenomas with recurrence (674; 98% hypermethylated), recurrent adenomas vs primary adenomas with and without recurrence (241; 99% hypermethylated) and colorectal adenomas vs normal mucosa (4179; 46% hypermethylated). DMPs in cytosine-phosphate-guanine (CpG) islands were frequently hypermethylated, whereas open sea- and shelf-regions exhibited hypomethylation. Gene ontology analysis revealed enrichment of genes associated with the immune system, inflammatory processes, and cancer pathways. In conclusion, our methylation data could assist in establishing a more robust and reproducible histological adenoma classification, which is a prerequisite for improving surveillance guidelines.

Single-cell genetic analysis of clonal dynamics in colorectal adenomas indicates CDX2 gain as a predictor of recurrence.

Colorectal adenomas are common precancerous lesions with the potential for malignant transformation to colorectal adenocarcinoma. Endoscopic polypectomy provides an opportunity for cancer prevention; however, recurrence rates are high. We collected formalin-fixed paraffin-embedded tissue of 15 primary adenomas with recurrence, 15 adenomas without recurrence, and 14 matched pair samples (primary adenoma and the corresponding recurrent adenoma). The samples were analysed by array-comparative genomic hybridisation (aCGH) and single-cell multiplex interphase fluorescence in situ hybridisation (miFISH) to understand clonal evolution, to examine the dynamics of copy number alterations (CNAs) and to identify molecular markers for recurrence prediction. The miFISH probe panel consisted of 14 colorectal carcinogenesis-relevant genes (COX2, PIK3CA, APC, CLIC1, EGFR, MYC, CCND1, CDX2, CDH1, TP53, HER2, SMAD7, SMAD4 and ZNF217), and a centromere probe (CEP10). The aCGH analysis confirmed the genetic landscape typical for colorectal tumorigenesis, that is, CNAs of chromosomes 7, 13q, 18 and 20q. Focal aberrations (≤10 Mbp) were mapped to chromosome bands 6p22.1-p21.33 (33.3%), 7q22.1 (31.4%) and 16q21 (29.4%). MiFISH detected gains of EGFR (23.6%), CDX2 (21.8%) and ZNF217 (18.2%). Most adenomas exhibited a major clone population which was accompanied by multiple smaller clone populations. Gains of CDX2 were exclusively seen in primary adenomas with recurrence (25%) compared to primary adenomas without recurrence (0%). Generation of phylogenetic trees for matched pair samples revealed four distinct patterns of clonal dynamics. In conclusion, adenoma development and recurrence are complex genetic processes driven by multiple CNAs whose evaluations by miFISH, with emphasis on CDX2, might serve as a predictor of recurrence.

A multicenter open-label phase II trial to evaluate nivolumab and ipilimumab for 2nd line therapy in elderly patients with advanced esophageal squamous cell cancer (RAMONA).

BACKGROUND: Advanced esophageal squamous cell cancer (ESCC) is frequently diagnosed in elderly patients. The impact of 2nd line chemotherapy is poorly defined. Recent data demonstrated effectiveness of checkpoint inhibitors in different squamous cell carcinomas. Therefore, we assess combined nivolumab/ipilimumab as 2nd line therapy in elderly ESCC patients. METHODS: RAMONA is a multicenter open-label phase II trial. The primary objective is to demonstrate a significant survival benefit of nivolumab/ipilimumab in advanced ESCC compared to historical data of standard chemotherapy. Primary endpoint is therefore overall survival (OS). Major secondary objective is the evaluation of tolerability. Time to QoL deterioration will thus be determined as key secondary endpoint. Further secondary endpoints are tumor response, PFS and safety. We aim to recruit a total of n = 75 subjects that have to be > 65 years old. Eligibility is determined by the geriatric status (G8 screening and Deficit Accumulation Frailty Index (DAFI)). A safety assessment will be performed after a 3 cycle run-in phase of nivolumab (240 mg Q2W) to justify escalation for eligible patients to combined nivolumab (240 mg Q2W) and ipilimumab (1 mg/kg Q6W), while the other patients will remain on nivolumab only. RAMONA also includes translational research sub-studies to identify predictive biomarkers, including PD-1 and PD-L1 evaluation at different time points, establishment of organoid cultures and microbiome analyses for response prediction. DISCUSSION: The RAMONA trial aims to implement checkpoint inhibitors for elderly patients with advanced ESCC as second line therapy. Novel biomarkers for checkpoint-inhibitor response are analyzed in extensive translational sub-studies. TRIAL REGISTRATION: EudraCT Number: 2017-002056-86 ; NCT03416244 , registered: 31.1.2018.

The effect of gender-specific invitation letters on utilization of colorectal cancer screening.

BACKGROUND AND AIM: Colorectal cancer (CRC) screening can effectively reduce cancer-associated mortality. In Germany, individuals over the age of 50 or 55 have access to CRC screening services. However, utilization rates are persistently low, particular in the male population. This observational study investigates the effect of standard versus gender-specific invitation letters on utilization of CRC screening services. METHODS: We analyzed utilization rates of individuals who were insured by a large health insurance fund in Bavaria, Germany. Persons who became eligible for CRC screening received a standard (2013-2014) or a gender-specific invitation letter (2015-2016). We compared utilization rates within 6 months after receipt of the invitation letter using billing codes of the health insurance fund. RESULTS: Invitation letters were sent to 49 535 individuals, of which 48.8 % were gender-specific. The overall utilization rate did not differ between recipients of the standard versus gender-specific invitation letter (11.6 % vs 11.1 %; RR: 0.97 [0.92-1.02], p = 0.19). However, uptake of screening colonoscopy was significantly higher among recipients of gender-specific invitations (2.9 % vs 3.5 %; RR: 1.21 [1.04-1.39], p = 0.01), whereas utilization of fecal occult blood tests declined (10.4 % vs 9.7 %; RR: 0.93 [0.88-0.99], p = 0.016). CONCLUSIONS: Gender-specific design of invitation letters can modify the patients' preference for specific CRC screening services and increase the acceptance of screening colonoscopy.

A multicenter phase 4 geriatric assessment directed trial to evaluate gemcitabine +/- nab-paclitaxel in elderly pancreatic cancer patients (GrantPax).

BACKGROUND: In the group of elderly patients (≥70 years) with metastatic pancreatic ductal adenocarcinoma (mPDAC), it is not known who benefits from intensive 1st line nab-paclitaxel/gemcitabine (nab-p/gem) combination chemotherapy or who would rather suffer from increased toxicity. We aim to determine whether treatment individualization by comprehensive geriatric assessments (CGAs) improves functional outcome of the patients. METHODS/DESIGN: GrantPax is a multicenter, open label phase 4 interventional trial. We use a CGA to stratify elderly patients into three parallel treatment groups (n = 45 per arm): 1) GOGO (nab-p/gem), 2) SLOWGO (gem mono) or 3) FRAIL (best supportive care). After the 1st cycle of chemotherapy (or 4 weeks in FRAIL group) another CGA and safety assessment is performed. CGA-stratified patients may not decline in their CGA performance in response to the first cycle of chemotherapy (primary objective), measured as a loss of 5 points or less in Barthels activities of daily living. Based on the second CGA, patients are re-assigned to their definite treatment arm and undergo further CGAs to monitor the course of treatment. Secondary endpoints include CGA scores during the course of therapy (CGA1-4), response rates, safety and survival rates. DISCUSSION: GrantPax is the first trial implementing a CGA-driven treatment to personalize therapy for elderly patients with pancreatic cancer. This may lead to standardization of therapy decisions for elderly patients and may optimize standard of care for this increasing group of patients. TRIAL REGISTRATION: NCT02812992 , registered 24.06.2016.

Diagnosing autoimmune pancreatitis with the Unifying-Autoimmune-Pancreatitis-Criteria.

BACKGROUND/OBJECTIVES: We had developed the Unifying-Autoimmune-Pancreatitis-Criteria (U-AIP) to diagnose autoimmune pancreatitis (AiP) within the M-ANNHEIM classification of chronic pancreatitis. In 2011, International-Consensus-Diagnostic-Criteria (ICDC) to diagnose AiP have been published. We had applied the U-AIP long before the ICDC were available. The aims of the study were, first, to describe patients with AiP diagnosed by the U-AIP; second, to compare diagnostic accuracies of the U-AIP and other diagnostic systems; third, to evaluate the clinical applicability of the U-AIP. METHODS: From 1998 until 2008, we identified patients with AiP using U-AIP, Japanese-, Korean-, Asian-, Mayo-HISORt-, Revised-Mayo-HISORt- and Italian-criteria. We retrospectively verified the diagnosis by ICDC and Revised-Japanese-2011-criteria, compared diagnostic accuracies of all systems and evaluated all criteria in consecutive patients with pancreatitis (2009 until 2010, Pancreas-Outpatient-Clinic-Cohort, n = 84). We retrospectively validated our diagnostic approach in consecutive patients with a pancreatic lesion requiring surgery (Surgical-Cohort, n = 98). RESULTS: Overall, we identified 21 patients with AiP. Unifying-Autoimmune-Pancreatitis-Criteria and ICDC presented the highest diagnostic accuracies (each 98.8%), highest Youden indices (each 0.95238), and highest proportions of diagnosed patients (each n = 20/21, U-AIP/ICDC vs. other diagnostic systems, p < 0.05, McNemar test). In the Pancreas-Outpatient-Clinic-Cohort, seven patients were diagnosed with AiP (n = 6 by U-AIP, n = 1 by Asian-criteria). International-Consensus-Diagnostic-Criteria confirmed the diagnosis in these individuals. Based on partial fulfillment of U-AIP, AiP was initially suspected in 13% (n = 10/77) of remaining patients from the Pancreas-Outpatient-Clinic-Cohort. In the Surgical-cohort, we identified one patient with AiP by U-AIP and ICDC. CONCLUSIONS: Unifying-Autoimmune-Pancreatitis-Criteria revealed a satisfactory clinical applicability and offered an additional approach to diagnose AiP.

Submucosal injection with waterjet improves endoscopic mucosal resection of colorectal adenoma - a randomised controlled clinical trial.

PURPOSE: Endoscopic mucosal resection (EMR) of colorectal adenomas leads to a reduced incidence of, and mortality from, colorectal carcinoma. Large adenomas are especially difficult to resect. Submucosal injection is a key part of EMR, as it allows for complete resection and decreased complications. We previously demonstrated in both animal models and a clinical trial that a focussed fluid beam applied to the mucosa creates selective fluid cushions in the submucosa selective tissue elevation by pressure (STEP). In this study, we examined the potential of this new technique compared to the standard inject and cut technique. METHODS: This was a monocentric prospective two armed randomised controlled clinical trial comparing the STEP technique to the standard needle injection. We included patients with Yamada I and II adenomas ≥12 mm. RESULTS: One hundred fifty-five patients were treated in the trial. With the STEP technique there was a significantly higher rate of en-bloc resection, whereas piecemeal resection was more common in the standard arm. The odds ratio of piecemeal resection was 2.422 with a 95% confidence interval of 1.163-5.045 (p value .0195). There was no significant difference in resection time between the two techniques, while there was a significant difference in resections speed for the STEP technique. There was also no difference in complication rates. CONCLUSIONS: This study demonstrated that the new STEP technique leads to a higher rate of en-bloc resections than the standard injection technique in endoscopic mucosa resection of colorectal adenomas. The STEP technique can play an important role in the future of EMR.

Multiple behavioral factors are associated with occurrence of large, flat colorectal polyps.

PURPOSE: The prevalence of advanced dysplasia and synchronous lesions is particularly high in patients with large, flat colorectal polyps. However, the impact of lifestyle on the development of such polyps is poorly investigated. Hence, this study aims to identify associations between behavioral factors and the occurrence of large, flat colorectal polyps. METHODS: Behavioral factors were retrospectively analyzed in patients with large, flat polyps and control patients with at most one diminutive polyp. Information on lifestyle factors, comorbidities, and demographic parameters were determined by a structured, self-administered questionnaire. RESULTS: Questionnaires of 350 patients with large, flat polyps and 489 control patients were included in the analysis. Most large, flat colorectal polyps contained adenoma with low-grade neoplasia and were located in the right colon. Multivariate analysis showed that advanced age (per 1-year increase-OR 1.09, CI 1.07-1.11, p < 0.0001), frequent cigarette smoking (OR 2.04, CI 1.25-3.32, p = 0.0041), daily consumption of red meat (OR 3.61, CI 1.00-12.96, p = 0.0492), and frequent bowel movements (OR 1.62, CI 1.13-2.33, p = 0.0093) were independent risk factors for occurrence of large, flat colorectal polyps. In contrast, frequent intake of cereals (OR 0.62, CI 0.44-0.88, p = 0.0074) was associated with a reduced risk. CONCLUSION: Multiple behavioral factors modulate the risk for developing large, flat colorectal polyps. This knowledge can be used to improve prevention of colorectal cancer.

Invitation letters increase participation in colorectal cancer screening - results from an observational study.

Background and Aim Participation rates in the German colorectal cancer screening program are low. Starting in 2013, a large health insurance plan in Bavaria, Germany, is sending an additional invitation letter to insured individuals when they turn 50 or 55 years and become eligible for participation in the program. The letter provides detailed information on colorectal cancer screening. We assessed the impact of the invitation letter on utilization rates. Methods Insurance claims data of a total of 48 343 individuals who had turned 50 or 55 years between 2012 to 2014 were reviewed for utilization rates of screening colonoscopy and fecal blood tests. Utilization rates 1 year prior (2012) and 2 years after introduction of the invitation letter (2013 and 2014) were compared. Furthermore, providers of colorectal cancer screening were determined. Results Within 6 months after turning 50 or 55 years, 8.8 - 10.2 % of all insured individuals participated in colorectal cancer screening, with the majority being females. After the introduction of the invitation letter, a moderate increase in participation rates could be observed (increase to 109 % [RR 101.7 - 117.3 %, p = 0.02] in 2014). The uptake rate of screening colonoscopy was significantly higher in recipients of the letter (increase to 138.4 % [RR 110.4 - 173.8 %, p = 0.0043] in 2013 and to 149 % [RR 119.5 - 186.3 %, p = 0.0003] in 2014). Furthermore, a significantly higher proportion of general practitioners and gastroenterologists provided colorectal cancer screening in individuals receiving the invitation letter. Conclusions Introduction of an invitation letter can improve participation rates for colorectal cancer screening.

Risk Factors for Local Recurrence of Large, Flat Colorectal Polyps after Endoscopic Mucosal Resection.

AIMS: Removal of large, flat colorectal polyps by endoscopic mucosal resection (EMR) is effective, but local recurrences occur regularly. This study investigated risk factors for local recurrence. METHOD: Cases of EMR of flat colorectal polyps ≥20 mm at an academic center from 2004 to 2011 were retrospectively analyzed for polyp features, resection technique, complications and local recurrences. Behavioral risk factors were retrospectively determined by self-administered questionnaires. RESULTS: Data were collected for 129 patients (57.3% male, mean age at time of EMR: 65.0 years). Mean polyp size was 37.2 mm. Polyps were mostly adenoma with low-grade dysplasia (58.1%) and predominantly located in the right colon (62%). En bloc resection was performed in 31.8%. The median follow-up time was 40 months. Local recurrence occurred in 26.3% of patients, with 87% being recurrence-free after 1 year (95% CI 81-93%). A history of smoking was reported by 51.6% of patients and 88.4% reported regular alcohol consumption. Univariate analysis showed that polyp size and piecemeal resection were associated with risk of local recurrence. In multivariate analysis, only polyp size was predictive for local recurrence. No association was found for behavioral risk factors. CONCLUSION: Polyp size is the main predictor of local recurrence after EMR of large, flat colorectal polyps.