[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.

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.

[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.

The drug-induced phenotypic landscape of colorectal cancer organoids.

Patient-derived organoids resemble the biology of tissues and tumors, enabling ex vivo modeling of human diseases. They have heterogeneous morphologies with unclear biological causes and relationship to treatment response. Here, we use high-throughput, image-based profiling to quantify phenotypes of over 5 million individual colorectal cancer organoids after treatment with >500 small molecules. Integration of data using multi-omics modeling identifies axes of morphological variation across organoids: Organoid size is linked to IGF1 receptor signaling, and cystic vs. solid organoid architecture is associated with LGR5 + stemness. Treatment-induced organoid morphology reflects organoid viability, drug mechanism of action, and is biologically interpretable. Inhibition of MEK leads to cystic reorganization of organoids and increases expression of LGR5, while inhibition of mTOR induces IGF1 receptor signaling. In conclusion, we identify shared axes of variation for colorectal cancer organoid morphology, their underlying biological mechanisms, and pharmacological interventions with the ability to move organoids along them.

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.

Sequential Geriatric Assessment in Older Patients with Colorectal Cancer during Chemotherapy: Subgroup Analysis of a Prospective, Multicenter Study EpiReal 75.

INTRODUCTION: Colorectal cancer (CRC) is a disease of older patients, but evidence-based guidelines for chemotherapy in older patients are scarce. Geriatric assessment (GA) evaluates a patient's functional status (FS) and helps in decision-making when choosing chemotherapy for older patients. However, the change of FS during chemotherapy is rarely studied as GA is mostly performed once instead of sequentially. METHODS: We performed a subgroup analysis of a prospective, multicenter study EpiReal 75. Patients aged ≥75 years with gastrointestinal malignancy prior to initiation of chemotherapy or receiving palliative chemotherapy were screened. We defined geriatric core assessments including the Eastern Cooperative Oncology Group score, Barthel's activities of daily living (ADL) scale, Lawton's instrumental activities of daily living (IADL) scale, and G-8 questionnaire, which were performed at baseline and repeated every 3 months. Quality of life (QoL) assessed by QLQ-C30 questionnaire was also re-evaluated every 3 months. We defined any deterioration in any of the geriatric parameters as unstable in the corresponding function. RESULTS: 28 patients with CRC were enrolled between April 2014 and December 2018. 20 patients were evaluable for statistical analysis with a mean age of 78.5 years (range, 75-88). Most patients received chemotherapy in palliative setting. During 3 months of chemotherapy, 25% of patients became more dependent as measured by ADL or IADL. During a median follow-up of 15 months, patients with unstable ADL or IADL had a significantly shorter overall survival (OS) than those with stable ADL or IADL (plogrank = 0.0055 and 0.0253, respectively), without a significant difference in progression-free survival (PFS). Also, unstable IADL correlated with a deterioration in aspects of QoL such as role functioning and emotional functioning (p = 0.0189 and 0.0239, respectively). 20% of patients experienced treatment-related grade 3 adverse events (AEs), no grade 4-5 AEs occurred. CONCLUSION: Sequential GA revealed changes in FS in older patients with CRC receiving chemotherapy. A deterioration of FS during chemotherapy did not influence PFS but had a negative impact on OS and QoL. It is therefore important to maintain FS in older patients with cancer, and regular performance of geriatric core assessments should be encouraged in the clinical practice.

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.

Neglected geriatric assessment and overtreatment of older patients with pancreatic cancer - Results from a prospective phase IV clinical trial.

BACKGROUND: Older patients with metastatic pancreatic cancer may suffer increased toxicity from intensive chemotherapy. Treatment individualization by geriatric assessment (GA) might improve functional outcome. METHODS: We performed a multicenter, phase IV, open label trial in patients ≥70 years with metastatic pancreatic adenocarcinoma. Patients underwent GA and were assigned to one of three categories based on their scores: Go-Go, Slow-Go, or Frail. These categories were intended to guide physician's treatment decisions when choosing to treat patients with nab-paclitaxel/gemcitabine (arm A), gemcitabine (arm B), or best supportive care (arm C). Primary objective was a stable (loss of five points or less) Barthel's Activities of Daily Living (ADL) score during chemotherapy; secondary endpoints included GA scores during therapy, safety, quality of life, response and survival rates. RESULTS: Thirty-two patients were enrolled in the trial in six centers in Germany (out of 135 planned), resulting in termination due to low recruitment. Fifteen patients were allocated to nab-paclitaxel/gemcitabine, fifteen to gemcitabine, and two to best supportive care by their physicians, although according to their GA scores 29 patients (91%) were categorized as Slow-Go and three (9%) as Go-Go. Thus, fifteen of 32 (47%) patients were misclassified and given a course of treatment inconsistent with their GA scores. Median progression-free survival (PFS) were 3.3 months and 9.1 months and median time to quality-of-life deterioration 13 days and 29 days in the nab-paclitaxel/gemcitabine and gemcitabine monotherapy arms, respectively. Serious adverse events were reported in 11 (78.6%) patients in the nab-paclitaxel/gemcitabine and 8 (53.3%) patients in the gemcitabine arm. CONCLUSIONS: Clinical evaluations by investigators differed markedly from geriatric assessments, leading to potential overtreatment. In our modest sample size study, those patients undergoing more intensive therapy had a less favorable course.

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.

Expression of the EGFR-RAS Inhibitory Proteins DOK1 and MTMR7 and its Significance in Colorectal Adenoma and Adenoma Recurrence.

BACKGROUND AND AIMS: Colorectal adenomas are precursor lesions for colorectal cancer (CRC), a major cause of cancer-related death. Despite all molecular insights, there are still unknown variables in the development of CRC as well as uncertainties regarding adenoma recurrence after resection. We aimed to characterize the expression of docking protein 1 (DOK1) and myotubularin-related protein 7 (MTMR7), which share inhibiting functions on EGFR-RAS-signalling, a major oncogenic driver in CRC, and their association with clinical variables and adenoma recurrence. METHODS: This observational study is based on clinical data obtained from patients who underwent routine endoscopy and consecutive follow-up examinations. Immunohistochemistry was conducted both in dysplastic tissue and adjacent non-dysplastic mucosa followed by microscopical assessment. Recurrence was differentiated between local, segmental and distant relapse. RESULTS: A total of 56 patients (23 females) gathering 96 adenomas/polyps were included. 36 patients experienced a metachronous lesion, 23 patients had simultaneous lesions in their index endoscopy. Female patients showed lower levels of MTMR7 in adenomas (p=0.0318). Adenomas of young patients showed lower DOK1 than those of older patients (p=0.0469). Big adenomas showed a higher expression of DOK1 than small lesions (p=0.0044). In serrated lesions, DOK1 was reduced (p=0.0026) and correlated with the quantity of lesions (p < 0.001). MTMR7 was significantly reduced in distant (p=0.05) and local segmental recurrence (p=0.0362), while DOK1 showed higher expression in recurrence (p=0.0291). CONCLUSIONS: We found ambivalent results regarding the role of the markers as potential tumor suppressors, implying a context-dependent function of these molecules which might change in the course of time. DOK1 may play an inhibiting role in the serrated pathway. Remarkably, molecular markers have the potential to predict recurrence, since a combined expression analysis of high DOK1 and low MTMR7 correlated with the likelihood of segmental adenoma recurrence.

Pancreatic Acinar Cell Carcinoma with Germline BRCA2 Mutation and Severe Pancreatic Panniculitis: A Case Report.

Pancreatic acinar cell carcinoma (ACC) is a rare malignant disease that displays distinct differences to pancreatic ductal adenocarcinoma. Here, we report the case of a patient with ACC and underlying breast cancer susceptibility gene 2 (BRCA2) germline mutation that developed severe pancreatic panniculitis (PP) during the course of the disease. The patient received a multimodal therapy including surgery, systemic chemotherapy, and targeted therapy with the PARP inhibitor olaparib, resulting in an overall survival of 47 months. Findings from this case are compared to the current knowledge on management of ACC and paraneoplastic PP.

Endoscopic Decompression in Colonic Distension.

BACKGROUND: Acute colonic distension is a medical emergency with high morbidity and mortality. Clinically important causes of colonic distension are acute colonic pseudo-obstruction, colonic volvulus, and malignant obstruction. Endoscopic decompression is one established therapeutic strategy. SUMMARY: This therapeutic review will give an overview of possible therapeutic strategies based on the recently published literature, focusing on endoscopic decompression and summarizing the other therapeutic possibilities. The review discusses separately the therapeutic options of acute colonic pseudo-obstruction, colonic volvulus, and malignant obstruction, providing an evidence-based orientation for clinical use. KEY MESSAGES: Endoscopic decompression of colonic distension is an established therapy with high clinical success. The technique and its position in the therapy sequence differ depending on the medical condition, the trigger of the colonic distension, and the local expertise.

PPARγ induces PD-L1 expression in MSS+ colorectal cancer cells.

Only a small subset of colorectal cancer (CRC) patients benefits from immunotherapies, comprising blocking antibodies (Abs) against checkpoint receptor "programmed-cell-death-1" (PD1) and its ligand (PD-L1), because most cases lack the required mutational burden and neo-antigen load caused by microsatellite instability (MSI) and/or an inflamed, immune cell-infiltrated PD-L1+ tumor microenvironment. Peroxisome proliferator-activated-receptor-gamma (PPARγ), a metabolic transcription factor stimulated by anti-diabetic drugs, has been previously implicated in pre/clinical responses to immunotherapy. We therefore raised the hypothesis that PPARγ induces PD-L1 on microsatellite stable (MSS) tumor cells to enhance Ab-target engagement and responsiveness to PD-L1 blockage. We found that PPARγ-agonists upregulate PD-L1 mRNA/protein expression in human gastrointestinal cancer cell lines and MSS+ patient-derived tumor organoids (PDOs). Mechanistically, PPARγ bound to and activated DNA-motifs similar to cognate PPARγ-responsive-elements (PPREs) in the proximal -2 kb promoter of the human PD-L1 gene. PPARγ-agonist reduced proliferation and viability of tumor cells in co-cultures with PD-L1 blocking Ab and lymphokine-activated killer cells (LAK) derived from the peripheral blood of CRC patients or healthy donors. Thus, metabolic modifiers improved the antitumoral response of immune checkpoint Ab, proposing novel therapeutic strategies for CRC.

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.

Cancer-Associated Mutations in Normal Colorectal Mucosa Adjacent to Sporadic Neoplasia.

INTRODUCTION: Colorectal cancer arises in a multistep process of carcinogenesis from normal mucosa. The earliest precursor might be a morphologically inconspicuous precancerous field, harboring cancer-associated mutations. METHODS: We systematically analyzed genetic alterations in 77 tissue samples from 30 patients with sporadic colorectal neoplasms (18 large adenomas and 12 adenocarcinomas) and matched adjacent normal mucosa (N = 30), as well as normal rectal tissue (N = 17). We profiled mutations associated with colorectal cancer by targeted sequencing of 46 genetic loci using 157 custom amplicons and a median depth of 42,655 reads per loci. RESULTS: Multiple mutations were found in colorectal neoplasms, most frequently in APC, KRAS, and TP53. In a subgroup of 11 of 30 patients, alterations were also detected in non-neoplastic mucosa. These mutations were divergent from those in matched neoplasms. The total alteration count and the allele frequency of mutations were higher in neoplasms compared with those in adjacent tissues. We found that younger patients (≤70 years) are less likely affected by mutations in non-neoplastic mucosa than older patients (>70 years, P = 0.013), although no association was found for other variables, including type, location and differentiation of neoplasia, and previous history of polyps. DISCUSSION: Our data show that cancer-associated mutations can be found in non-neoplastic tissues in a subgroup of patients with colorectal neoplasms. Further studies are needed to specify the risk of occurrence and recurrence of neoplasia in this patient population.

Complete Remission of Metastatic HER2+ Oesophagogastric Junctional Adenocarcinoma under long-term Trastuzumab Treatment.

Metastatic gastric cancer (GC) and oesophagogastric junctional (OGJ) adenocarcinoma have a poor clinical outcome with a high worldwide burden of disease. A 65-year old male patient with microcytic anemia was diagnosed with stage IV OGJ adenocarcinoma with multiple liver metastases. Immunohistochemical analysis revealed a high expression of HER2 (3+). Palliative chemotherapy with FLOT (oxaliplatin, 5-fluorouracil, leucovorin and docetaxel) in combination with trastuzumab was initiated. Due to severe adverse events, the therapy was de-escalated to trastuzumab monotherapy after six months of treatment. Initial restaging revealed partial response after the combination therapy of FLOT with trastuzumab. After reduction to trastuzumab monotherapy, the disease remained stable for two years until radiological complete response was observed. Trastuzumab monotherapy was continued for another two years to maintain complete response. Eleven months after the discontinuation of the therapy, no recurrence of the disease was detected. In conclusion, complete response can be achieved under trastuzumab monotherapy in exceptional responders.

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.

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.

Detection of mutational patterns in cell-free DNA of colorectal cancer by custom amplicon sequencing.

Monitoring the mutational patterns of solid tumors during cancer therapy is a major challenge in oncology. Analysis of mutations in cell-free (cf) DNA offers a noninvasive approach to detect mutations that may be prognostic for disease survival or predictive for primary or secondary drug resistance. A main challenge for the application of cfDNA as a diagnostic tool is the diverse mutational landscape of cancer. Here, we developed a flexible end-to-end experimental and bioinformatic workflow to analyze mutations in cfDNA using custom amplicon sequencing. Our approach relies on open-software tools to select primers suitable for multiplex PCR using minimal cfDNA as input. In addition, we developed a robust linear model to identify specific genetic alterations from sequencing data of cfDNA. We used our workflow to design a custom amplicon panel suitable for detection of hotspot mutations relevant for colorectal cancer and analyzed mutations in serial cfDNA samples from a pilot cohort of 34 patients with advanced colorectal cancer. Using our method, we could detect recurrent and patient-specific mutational patterns in the majority of patients. Furthermore, we show that dynamic changes of mutant allele frequencies in cfDNA correlate well with disease progression. Finally, we demonstrate that sequencing of cfDNA can reveal mechanisms of resistance to anti-Epidermal Growth Factor Receptor(EGFR) antibody treatment. Thus, our approach offers a simple and highly customizable method to explore genetic alterations in cfDNA.