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In the surgical treatment of colorectal carcinoma (CRC), 1 in 10 patients has a peritumorous adhesion or tumor infiltration in the adjacent tissue or organs. Accordingly, multivisceral resection (MVR) must be performed in these patients. This prospective multicenter observational study aimed to analyze the possible differences between non-multivisceral resection (nMVR) and MVR in terms of early postoperative and long-term oncological treatment outcomes. We also aimed to determine the factors influencing overall survival.

Inflammatory reactions caused by immunosuppression appear a particular interesting disease due to its very specific and partly unclear etiopathogenesis.

Glioblastoma (GBM) is the most commonly occurring and most aggressive primary brain tumor. Transcriptomics-based tumor subtype classification has established the mesenchymal lineage of GBM (MES-GBM) as cancers with particular aggressive behavior and high levels of therapy resistance. Previously it was show that Trihexyphenidyl (THP), a market approved M1 muscarinic receptor-targeting oral drug can suppress proliferation and survival of GBM stem cells from the classical transcriptomic subtype. In a series of in vitro experiments, this study confirms the therapeutic potential of THP, by effectively suppressing the growth, proliferation and survival of MES-GBM cells with limited effects on non-tumor cells. Transcriptomic profiling of treated cancer cells identified genes and associated metabolic signaling pathways as possible underlying molecular mechanisms responsible for THP-induced effects. In vivo trials of THP in immunocompromised mice carry orthotopic MES-GBMs showed moderate response to the drug. This study further highlights the potential of THP repurposing as an anti-cancer treatment regimen but mode of action and d optimal treatment procedures for in vivo regimens need to be investigated further. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most commonly occurring and most aggressive primary brain tumor. Transcriptomics-based tumor subtype classification has established the mesenchymal lineage of GBM (MES-GBM) as cancers with particular aggressive behavior and high levels of therapy resistance. Previously it was show that Trihexyphenidyl (THP), a market approved M1 muscarinic receptor-targeting oral drug can suppress proliferation and survival of GBM stem cells from the classical transcriptomic subtype. In a series of in vitro experiments, this study confirms the therapeutic potential of THP, by effectively suppressing the growth, proliferation and survival of MES-GBM cells with limited effects on non-tumor cells. Transcriptomic profiling of treated cancer cells identified genes and associated metabolic signaling pathways as possible underlying molecular mechanisms responsible for THP-induced effects. In vivo trials of THP in immunocompromised mice carry orthotopic MES-GBMs showed moderate response to the drug. This study further highlights the potential of THP repurposing as an anti-cancer treatment regimen but mode of action and d optimal treatment procedures for in vivo regimens need to be investigated further. [ABSTRACT FROM AUTHOR]

Background: In this retrospective study, we evaluate the diagnostic utility of C-reactive protein (CRP) and leucocyte count within the EAES 2015 guidelines for acute appendicitis (AA) in differentiating uncomplicated (UAA) from complicated AA (CAA). Methods: Conducted at a tertiary care center in Germany, the study included 285 patients over 18 years who were diagnosed with AA from January 2019 to December 2021. Patient data included demographics, inflammatory markers, and postoperative outcomes. Results: CRP levels (Md: 60.2 mg/dL vs. 10.5 mg/dL; p < 0.001) and leucocyte count (Md: 14.4 Gpt/L vs. 13.1 Gpt/L; p = 0.016) were higher in CAA. CRP had a medium diagnostic value for detecting CAA (AUC = 0.79), with a cutoff at 44.3 mg/L, making it more likely to develop CAA. Leucocyte count showed low predictive value for CAA (AUC = 0.59). CRP ≥ 44.3 mg/L was associated with a higher risk of postoperative complications (OR: 2.9; p = 0.002) and prolonged hospitalization (OR: 3.5; p < 0.001). Conclusions: CRP, within the context of the EAES classification, presents as a valuable diagnostic marker to distinguish CAA from UAA, with a higher risk of postoperative complications and hospitalization. Leucocyte count showed low diagnostic value for the identification of CAA. [ABSTRACT FROM AUTHOR]

Background/Objectives: In patients diagnosed with uncomplicated acute appendicitis (UAA), the absence of calcified deposits or stones, called appendicoliths, often leads to consideration of non-operative treatment (NOT), despite the notable treatment failure rate associated with this approach. Previous research has indirectly estimated the prevalence of appendicoliths to range between 15% and 38% retrospectively by CT scan, intraoperative palpation, and pathology report, thereby potentially missing certain concrements. Our hypothesis proposes that this reported prevalence significantly underestimates the occurrence of appendicoliths, which could explain the high failure rate of 29% of patients with appendicitis observed with NOT. Methods: In our prospective study, conducted with a cohort of 56 adult patients diagnosed with acute appendicitis (AA), we employed intraoperative extracorporeal incisions of the vermiform appendix, in addition to standard diagnostic methods. Results: Our findings revealed 50% more appendicoliths by intraoperative incision (n = 36, p < 0.001) compared to preoperative imaging (n = 24). Appendicoliths were present in 71.4% (n = 40, p < 0.001) of AA patients. Conclusions: These results suggest that conventional diagnostic procedures plausibly underestimate the actual prevalence of appendicoliths, potentially elucidating the frequent treatment failures observed in NOT approaches applied to patients with UAA. [ABSTRACT FROM AUTHOR]

l-Ornithine- l-aspartate (LOLA) reduces toxic ammonium (NH3) plasma levels in hepatic encephalopathy. NH3 detoxification/excretion is achieved by its incorporation into urea and glutamine via activation of carbamoyl phosphate synthetase 1 (CSP1) by l-ornithine and stimulation of arginase by l-aspartate. We aimed at identifying additional molecular targets of LOLA as a potential treatment option for non-alcoholic fatty liver disease (NAFLD). In primary hepatocytes from NAFLD patients, urea cycle enzymes CSP1 and ornithine transcarbamylase (OTC) increase, while the catabolism of branched-chain amino acids (BCAAs) decreases with disease severity. In contrast, LOLA increased the expression rates of the BCAA enzyme transcripts bcat2, bckdha, and bckdk. In untreated HepG2 hepatoblastoma cells and HepG2-based models of steatosis, insulin resistance, and metabolic syndrome (the latter for the first time established herein), LOLA reduced the release of NH3; beneficially modulated the expression of genes related to fatty acid import/transport (cd36, cpt1), synthesis (fasn, scd1, ACC1), and regulation (srbf1); reduced cellular ATP and acetyl-CoA; and favorably modulated the expression of master regulators/genes of energy balance/mitochondrial biogenesis (AMPK-α, pgc1α). Moreover, LOLA reconstituted the depolarized mitochondrial membrane potential, while retaining mitochondrial integrity and avoiding induction of superoxide production. Most effects were concentration-dependent at ≤40 mM LOLA. We demonstrate for l-ornithine-l-aspartate a broad range of reconstituting effects on metabolic carriers and targets of catabolism/energy metabolism impaired in NAFLD. These findings strongly advocate further investigations to establish LOLA as a safe, efficacious, and cost-effective basic medication for preventing and/or alleviating NAFLD. [ABSTRACT FROM AUTHOR]

The definition of complete mesocolic excision (CME) for colon carcinomas revolutionized the way of colon surgery. This technique conquered the world starting from Erlangen. Nevertheless, currently new developments especially in minimally invasive surgery challenge CME to become settled as a standard of care. To understand the evolution of CME, anatomical details occurring during embryogenesis and their variations have to be considered. This knowledge is indispensable to transfer CME from an open to a minimally invasive setting. Conventional surgery for colon cancer (non-CME) has a morbidity of 12.1–28.5% and a 3.7% mortality risk vs. 12–36.4% morbidity and 2.1–3% mortality for open CME. The morbidity of laparoscopic CME is between 4 and 31% with a mortality of 0.5–0.9%. In robotic assisted surgery, morbidity between 10 and 25% with a mortality of 1% was published. The cancer-related survival after 3 and 5 years for open CME is respectively 91.3–95% and 90% vs. 87% and 74% for non-CME. For laparoscopic CME the 3- and 5-year cancer-related survival is 87.8–97% and 79.5–80.2%. In stage UICC III the 3- and 5-year cancer-related survival is 83.9% and 80.8% in the Erlangen data of open technique vs. 75.4% and 65.5–71.7% for laparoscopic surgery. For stage UICC III the 3- and 5-year local tumor recurrence is 3.8%. The published data and the results from Erlangen demonstrate that CME is safe in experienced hands with no increased morbidity. It offers an obvious survival benefit for the patients which can be achieved solely by surgery. Teaching programs are needed for minimally invasive CME to facilitate this technique in the same quality compared to open surgery. Passing these challenges CME will become the standard of care for patients with colon carcinomas offering all benefits of minimally invasive surgery and oncological outcome.

Different tumor microenvironments (TMEs) induce stromal cell plasticity that affects tumorigenesis. The impact of TME-dependent heterogeneity of tumor endothelial cells (TECs) on tumorigenesis is unclear. Here, we isolated pure TECs from human colorectal carcinomas (CRCs) that exhibited TMEs with either improved (Th1-TME CRCs) or worse clinical prognosis (control-TME CRCs). Transcriptome analyses identified markedly different gene clusters that reflected the tumorigenic and angiogenic activities of the respective TMEs. The gene encoding the matricellular protein SPARCL1 was most strongly upregulated in Th1-TME TECs. It was also highly expressed in ECs in healthy colon tissues and Th1-TME CRCs but low in control-TME CRCs. In vitro, SPARCL1 expression was induced in confluent, quiescent ECs and functionally contributed to EC quiescence by inhibiting proliferation, migration, and sprouting, whereas siRNA-mediated knockdown increased sprouting. In human CRC tissues and mouse models, vessels with SPARCL1 expression were larger and more densely covered by mural cells. SPARCL1 secretion from quiescent ECs inhibited mural cell migration, which likely led to stabilized mural cell coverage of mature vessels. Together, these findings demonstrate TME-dependent intertumoral TEC heterogeneity in CRC. They further indicate that TEC heterogeneity is regulated by SPARCL1, which promotes the cell quiescence and vessel homeostasis contributing to the favorable prognoses associated with Th1-TME CRCs., Introduction The clonal evolvement of tumors by sequential mutation causes the genotypic heterogeneity of tumor cells (1). In addition, the detection of cancer stem cells demonstrated that tumor cells exhibit [...]

Abstract Background Accurate histopathological evaluation of resected lymph nodes (LN) is essential for the reliable staging of colorectal carcinomas (CRC). With conventional sectioning and staining techniques usually only parts of the LN are examined which might lead to incorrect tumor staging. A molecular method called OSNA (One Step Nucleic Acid Amplification) may be suitable to determine the metastatic status of the complete LN and therefore improve staging. Methods OSNA is based on a short homogenisation step and subsequent automated amplification of cytokeratin 19 (CK19) mRNA directly from the sample lysate, with result available in 30-40 minutes. In this study 184 frozen LN from 184 patients with CRC were investigated by both OSNA and histology (Haematoxylin & Eosin staining and CK19 immunohistochemistry), with half of the LN used for each method. Samples with discordant results were further analysed by RT-PCR for CK19 and carcinoembryonic antigen (CEA). Results The concordance rate between histology and OSNA was 95.7%. Three LN were histology+/OSNA- and 5 LN histology-/OSNA+. RT-PCR supported the OSNA result in 3 discordant cases, suggesting that metastases were exclusively located in either the tissue analysed by OSNA or the tissue used for histology. If these samples were excluded the concordance was 97.2%, the sensitivity 94.9%, and the specificity 97.9%. Three patients (3%) staged as UICC I or II by routine histopathology were upstaged as LN positive by OSNA. One of these patients developed distant metastases (DMS) during follow up. Conclusion OSNA is a new and reliable method for molecular staging of lymphatic metastases in CRC and enables the examination of whole LN. It can be applied as a rapid diagnostic tool to estimate tumour involvement in LN during the staging of CRC.

Abstract Background To identify early symptoms of familial adenomatous polyposis with a view to improve early diagnosis and treatment. Diagnosis on the basis of genetic testing is usually limited to where there is a known family history, so FAP is more usually diagnosed on clinical grounds. Except for those identified via FAP registers, the majority of patients are symptomatic at the time of diagnosis. Methods We undertook a retrospective study of 143 FAP patients treated at the Department of Surgery, University of Erlangen between 1971 and 2000. We identified patterns of symptoms, endoscopic findings and extracolonic manifestations in three age groups. Results FAP was diagnosed clinically on the basis of symptoms in 84% (120/143) of these patients. Most presented with intestinal symptoms such as colonic bleeding (68%) and diarrhea (42%). All but one of the patients between 20 and 40 years old had rectal polyps (98.7%, 75/76), whereas in those over 40 years old the prevalence was 76% (35/46). Non-specific symptoms such as abdominal pain, fatigue and bloating were less frequent and were mainly reported by patients older than 40. Conclusion The commonest presenting features of FAP are alteration of bowel habit and rectal bleeding, but both are found in many other conditions. Patients with these findings need immediate endoscopy to allow prompt diagnosis and prophylactic surgery.

1. Introduction Microarray-based investigations of genome wide gene expression have become a popular method for the molecular characterisation of various tissue types. In molecular oncology prognosis-related genes could be identified [...], Microarray analysis reaches increasing popularity during the investigation of prognostic gene clusters in oncology. The standardisation of technical procedures will be essential to compare various datasets produced by different research groups. In several projects the amount of available tissue is limited. In such cases the preamplification of RNA might be necessary prior to microarray hybridisation. To evaluate the comparability of microarray results generated either by amplified or non amplified RNA we isolated RNA from colorectal cancer samples (stage UICC IV) following tumour tissue enrichment by macroscopic manual dissection (CMD). One part of the RNA was directly labelled and hybridised to GeneChips (HG-U133A, Affymetrix), the other part of the RNA was amplified according to the 'Eberwine' protocol and was then hybridised to the microarrays. During unsupervised hierarchical clustering the samples were divided in groups regarding the RNA pre-treatment and 5.726 differentially expressed genes were identified. Using independent microarray data of 31 amplified vs. 24 non amplified RNA samples from colon carcinomas (stage UICC III) in a set of 50 predictive genes we validated the amplification bias. In conclusion microarray data resulting from different pre-processing regarding RNA pre-amplification can not be compared within one analysis. Copyright © 2009 Roland S. Croner et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Introduction: Complete mesocolic excision (CME) is generally accepted as state of the art in colon cancer surgery. However, the long-term impact of CME has not been systematically examined. Therefore cohort studies might be a possible way to clarify any differences between conventional resections and CME. Following bilateral cooperation between the Department of Surgery/University Hospital of Erlangen and the 1st Surgical Department of the General Hospital of Nikaia/Piraeus, including teaching activities for introduction of CME, a cohort study was performed, considering surgical quality criteria and clinical outcome.Material and Methods: All patients with colon carcinomas (CME group, n = 31) referred to the 1st Surgical Department of General Hospital, Nikaia/Piraeus, Greece for surgery from January 2012 to December 2013 were prospectively analyzed and compared with patients who underwent conventional surgery for colon cancer between January 2008 and December 2011 (non-CME group, n = 35). Patients' follow-up was at least 48 months.Results: There were significantly better results in terms of lymph node yield (CME group: 29.6 vs. non-CME group: 17.85; p < 0.001) and lymph node ratio (LNR) (CME group: 0.12 vs. non-CME group: 0.24; p < 0.001) and recurrence-free survival in favor of the CME group (CME group: n = 0 vs. non-CME group: n = 5) without any increase in surgical morbidity (CME group: n = 6 vs. non-CME group: n = 11; p = 0.10).Conclusions: Complete mesocolic excision appears to offer a superior oncological result without any increase of postoperative morbidity and mortality. Furthermore, CME represents a surgical technique which can be established in a surgical department after previous teaching without increasing the postoperative complication rate. [ABSTRACT FROM AUTHOR]