Survival rates and prognostic factors in right- and left-sided colon cancer stage I–IV: an unselected retrospective single-center trial

Purpose: Colorectal cancer revealed over the last decades a remarkable shift with an increasing proportion of a right- compared to a left-sided tumor location. In the current study, we aimed to disclose clinicopathological differences between right- and left-sided colon cancer (rCC and lCC) with respect to mortality and outcome predictors. Methods: In total, 417 patients with colon cancer stage I-IV were analyzed in the present retrospective single-center study. Survival rates were assessed using the Kaplan-Meier method and uni/multivariate analyses were performed with a Cox proportional hazards regression model. Results: Our study showed no significant difference of the overall survival between rCC and lCC stage I-IV (p = 0.354). Multivariate analysis revealed in the rCC cohort the worst outcome for ASA (American Society of Anesthesiologists) score IV patients (hazard ratio [HR]: 16.0; CI 95%: 2.1-123.5), CEA (carcinoembryonic antigen) blood level > 100 mu g/l (HR: 3.3; CI 95%: 1.2-9.0), increased lymph node ratio of 0.6-1.0 (HR: 5.3; CI 95%: 1.7-16.1), and grade 4 tumors (G4) (HR: 120.6; CI 95%: 6.7-2179.6) whereas in the lCC population, ASA score IV (HR: 8.9; CI 95%: 0.9-91.9), CEA blood level 20.1-100 mu g/l (HR: 5.4; CI 95%: 2.4-12.4), conversion to laparotomy (HR: 14.1; CI 95%: 4.0-49.0), and severe surgical complications (Clavien-Dindo III-IV) (HR: 2.9; CI 95%: 1.5-5.5) were identified as predictors of a diminished overall survival. Conclusion: Laterality disclosed no significant effect on the overall prognosis of colon cancer patients. However, group differences and distinct survival predictors could be identified in rCC and lCC patients

Risk factors for upper and lower type prolonged postoperative ileus following surgery for Crohn’s disease

Purpose: Prolonged postoperative ileus (PPOI) is common after bowel resections, especially in Crohn's disease (CD). The pathophysiology of PPOI is not fully understood. PPOI could affect only the upper or lower gastrointestinal (GI) tract. The aim of this study was to assess risk factors for diverse types of PPOI, particularly to differentiate PPOI of upper and lower GI tract. Methods: A retrospective analysis of 163 patients with CD undergoing ileocecal resection from 2015 to 2020 in a single center was performed. PPOI of the upper GI tract was predefined as the presence of vomiting or use of nasogastric tube longer than the third postoperative day. Lower PPOI was predefined as the absence of defecation for more than three days. Independent risk factors were identified by multivariable logistic regression analysis. Results: Overall incidence of PPOI was 42.7%. PPOI of the upper GI tract was observed in 30.7% and lower PPOI in 20.9% of patients. Independent risk factors for upper PPOI included older age, surgery by a resident surgeon, hand-sewn anastomosis, prolonged opioid analgesia, and reoperation, while for lower PPOI included BMI <= 25 kg/m(2), preoperative anemia, and absence of ileostomy. Conclusion: This study identified different risk factors for upper and lower PPOI after ileocecal resection in patients with CD. A differentiated upper/lower type approach should be considered in future research and clinical practice. High-risk patients for each type of PPOI should be closely monitored, and modifiable risk factors, such as preoperative anemia and opioids, should be avoided if possible

Peptide Signatures for Prognostic Markers of Pancreatic Cancer by MALDI Mass Spectrometry Imaging

Simple Summary: Pancreatic cancer remains one of the most lethal tumor entities worldwide given its overall 5-year survival after diagnosis of 9%. Thus, further understanding of molecular changes to improve individual prognostic assessment as well as diagnostic and therapeutic advancement is crucial. The aim of this study was to investigate the feasibility of Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to identify specific peptide signatures linked to established prognostic parameters of pancreatic cancer. In a patient cohort of 18 patients with exocrine pancreatic cancer after tumor resection, MALDI imaging analysis additional to histopathological assessment was performed. Applying this method to tissue sections of the tumors, we were able to identify discriminative peptide signatures corresponding to nine proteins for the prognostic histopathological features lymphatic vessel invasion, lymph node metastasis and angioinvasion. This demonstrates the technical feasibility of MALDI-MSI to identify peptide signatures with prognostic value through the workflows used in this study. Abstract: Despite the overall poor prognosis of pancreatic cancer there is heterogeneity in clinical courses of tumors not assessed by conventional risk stratification. This yields the need of additional markers for proper assessment of prognosis and multimodal clinical management. We provide a proof of concept study evaluating the feasibility of Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to identify specific peptide signatures linked to prognostic parameters of pancreatic cancer. On 18 patients with exocrine pancreatic cancer after tumor resection, MALDI imaging analysis was performed additional to histopathological assessment. Principal component analysis (PCA) was used to explore discrimination of peptide signatures of prognostic histopathological features and receiver operator characteristic (ROC) to identify which specific m/z values are the most discriminative between the prognostic subgroups of patients. Out of 557 aligned m/z values discriminate peptide signatures for the prognostic histopathological features lymphatic vessel invasion (pL, 16 m/z values, eight proteins), nodal metastasis (pN, two m/z values, one protein) and angioinvasion (pV, 4 m/z values, two proteins) were identified. These results yield proof of concept that MALDI-MSI of pancreatic cancer tissue is feasible to identify peptide signatures of prognostic relevance and can augment risk assessment

Novel methods for in vitro modeling of pancreatic cancer reveal important aspects for successful primary cell culture

Background: Pancreatic cancer remains a fatal disease. Experimental systems are needed for personalized treatment strategies, drug testing and to further understand tumor biology. Cell cultures can serve as an excellent preclinical platform, but their generation remains challenging. Methods: Tumor cells from surgically removed pancreatic ductal adenocarcinoma (PDAC) specimens were cultured under novel protocols. Cellular growth and composition were analyzed and culture conditions were continuously optimized. Characterization of cell cultures and primary tumors was performed via hematoxylin and eosin (HE) and immunofluorescence (IF) staining. Results: Protocols for two- and three-dimensional PDAC primary cell cultures could successfully be established. Primary cell culture depended on dissociation techniques, growth factor supplementation and extracellular matrix components containing Matrigel being crucial for the transformation to three-dimensional PDAC organoids. The generated cultures showed to be highly resemblant to established PDAC primary cell cultures. HE and IF staining for cell culture and corresponding primary tumor characterization could successfully be performed. Conclusions: The work presented herein shows novel and effective methods to successfully establish primary PDAC cell cultures in a distinct time frame. Factors contributing to cell growth and differentiation could be identified with important implications for further primary cell culture protocols. The established protocols might serve as novel tools in personalized tumor therapy

A census of cell types and paracrine interactions in colorectal cancer

In colorectal cancer, oncogenic mutations transform a hierarchically organized and homeostatic epithelium into invasive cancer tissue. To define differences in cellular composition between the normal colon and colorectal cancer, and to map potential cellular interactions between tumor cells and their microenvironment, we profiled transcriptomes of >50,000 single cells from tumors and matched normal tissues of eight colorectal cancer patients. We find that tumor formation is accompanied by changes in epithelial, immune and stromal cell compartments in all patients. In the epithelium, we identify a continuum of five tumor-specific stem cell and progenitor-like populations, and persistent multilineage differentiation. We find multiple stromal and immune cell types to be consistently expanded in tumor compared to the normal colon, including cancer-associated fibroblasts, pericytes, monocytes, macrophages and a subset of T cells. We identify epithelial tumor cells and cancer-associated fibroblasts as relevant for assigning colorectal cancer consensus molecular subtypes. Our survey of growth factors in the tumor microenvironment identifies cell types responsible for increased paracrine EGFR, MET and TGF-β signaling in tumor tissue compared to the normal colon. We show that matched colorectal cancer organoids retain cell type heterogeneity, allowing to define a distinct differentiation trajectory encompassing stem and progenitor-like tumor cells. In summary, our single-cell analyses provide insights into cell types and signals shaping colorectal cancer cell plasticity

Impact of myopenia and myosteatosis on postoperative outcome and recurrence in Crohn’s disease

PURPOSE: Myopenia and myosteatosis have been proposed to be prognostic factors of surgical outcomes for various diseases, but their exact role in Crohn’s disease (CD) is unknown. The aim of this study is to evaluate their impact on anastomotic leakage, CD recurrence, and postoperative complications after ileocecal resection in patients with CD. METHODS: A retrospective analysis of CD patients undergoing ileocecal resection at our tertiary referral center was performed. To assess myopenia, skeletal muscle index (skeletal muscle area normalized for body height) was measured using an established image analysis method at third lumbar vertebra level on MRI cross-sectional images. Muscle signal intensity was measured to assess myosteatosis index. RESULTS: A total of 347 patients were retrospectively analyzed. An adequate abdominal MRI scan within 12 months prior to surgery was available for 223 patients with median follow-up time of 48.8 months (IQR: 20.0–82.9). Anastomotic leakage rate was not associated with myopenia (SMI: p = 0.363) or myosteatosis index (p = 0.821). Patients with Crohn’s recurrence had a significantly lower SMI (p = 0.047) in univariable analysis, but SMI was not an independent factor for recurrent anastomotic stenosis in multivariable analysis (OR 0.951, 95% CI 0.840–1.078; p = 0.434). Postoperative complications were not associated with myopenia or myosteatosis. CONCLUSION: Based on the largest cohort of its kind with a long follow-up time, we could provide some data that MRI parameters for myopenia and myosteatosis may not be reliable predictors of postoperative outcome or recurrence in patients with Crohn’s disease undergoing ileocecal resection

The impact of surgical site infection—a cost analysis

Purpose: Surgical site infection (SSI) occurs in up to 25% of patients after elective laparotomy. We aimed to determine the effect of SSI on healthcare costs and patients' quality of life. Methods: In this post hoc analysis based on the RECIPE trial, we studied a 30-day postoperative outcome of SSI in a single-center, prospective randomized controlled trial comparing subcutaneous wound irrigation with 0.04% polyhexanide to 0.9% saline after elective laparotomy. Total medical costs were analyzed accurately per patient with the tool of our corporate controlling team which is based on diagnosis-related groups in Germany. Results: Between November 2015 and May 2018, 456 patients were recruited. The overall rate of SSI was 28.2%. Overall costs of inpatient treatment were higher in the group with SSI: median 16.685 euro; 19.703 USD (IQR 21.638 euro; 25.552 USD) vs. median 11.235 euro; 13.276 USD (IQR 11.564 euro; 13.656 USD); p < 0.001. There was a difference in surgery costs (median 6.664 euro; 7.870 USD with SSI vs. median 5.040 euro; 5.952 USD without SSI; p = 0.001) and costs on the surgical ward (median 8.404 euro; 9.924 USD with SSI vs. median 4.690 euro; 5.538 USD without SSI; p < 0.001). Patients with SSI were less satisfied with the cosmetic result (4.3% vs. 16.2%; p < 0.001). Overall costs for patients who were irrigated with saline were median 12.056 euro; 14.237 USD vs. median 12.793 euro; 15.107 USD in the polyhexanide group (p = 0.52). Conclusion: SSI after elective laparotomy increased hospital costs substantially. This is an additional reason why the prevention of SSI is important. Overall costs for intraoperative wound irrigation with saline were comparable with polyhexanide

Rethinking the TNM Classification Regarding Direct Lymph Node Invasion in Pancreatic Ductal Adenocarcinoma

Mechanisms of lymph node invasion seem to play a prognostic role in pancreatic ductal adenocarcinoma (PDAC) after resection. However, the 8th edition of the TNM classification of the American Joint Committee on Cancer (AJCC) does not consider this. The aim of this study was to analyse the prognostic role of different mechanisms of lymph node invasion on PDAC. One hundred and twenty-two patients with resected PDAC were examined. We distinguished three groups: direct (per continuitatem, Nc) from the main tumour, metastasis (Nm) without any contact to the main tumour, and a mixed mechanism (Ncm). Afterwards, the prognostic power of the different groups was analysed concerning overall survival (OS). In total, 20 patients displayed direct lymph node invasion (Nc = 16.4%), 44 were classed as Nm (36.1%), and 21 were classed as Ncm (17.2%). The difference in OS was not statistically significant between N0 (no lymph node metastasis, n = 37) and Nc (p = 0.134), while Nm had worse OS than N0 (p < 0.001). Direct invasion alone had no statistically significant effect on OS (p = 0.885). Redefining the N0 stage by including Nc patients showed a more precise OS prediction among N stages (p = 0.001 vs. p = 0.002). Nc was more similar to N0 than to Nm; hence, we suggest a rethinking of TNM classification based on the mechanisms of lymph node metastases in PDAC. Overall, this novel classification is more precise

The optimal cut-off values for tumor size, number of lesions, and CEA levels in patients with surgically treated colorectal cancer liver metastases: An international, multi-institutional study

Background and Objectives Despite the long-standing consensus on the importance of tumor size, tumor number and carcinoembryonic antigen (CEA) levels as predictors of long-term outcomes among patients with colorectal liver metastases (CRLM), optimal prognostic cut-offs for these variables have not been established. Methods Patients who underwent curative-intent resection of CRLM and had available data on at least one of the three variables of interest above were selected from a multi-institutional dataset of patients with known KRAS mutational status. The resulting cohort was randomly split into training and testing datasets and recursive partitioning analysis was employed to determine optimal cut-offs. The concordance probability estimates (CPEs) for these optimal cut offs were calculated and compared to CPEs for the most widely used cut-offs in the surgical literature. Results A total of 1643 patients who met eligibility criteria were identified. Following recursive partitioning analysis in the training dataset, the following cut-offs were identified: 2.95 cm for tumor size, 1.5 for tumor number and 6.15 ng/ml for CEA levels. In the entire dataset, the calculated CPEs for the new tumor size (0.52), tumor number (0.56) and CEA (0.53) cut offs exceeded CPEs for other commonly employed cut-offs. Conclusion The current study was able to identify optimal cut-offs for the three most commonly employed prognostic factors in CRLM. While the per variable gains in discriminatory power are modest, these novel cut-offs may help produce appreciable increases in prognostic performance when combined in the context of future risk scores.publishedVersio