Exokrine Pankreasinsuffizienz

Zusammenfassung. Die exokrine Pankreasinsuffizienz ist als Verdauungsstörung in Folge einer verminderten pankreatischen Enzym- und Bikarbonatsekretion definiert. Der nicht kompensierbare Ausfall der Pankreaslipase verursacht ein durch Steatorrhoe, Vitaminmangel und Gewichtsverlust gekennzeichnetes Malabsorptionssyndrom. Die Ursachen sind chronische Pankreatitis, Pankreastumore, Zystische Fibrose sowie extrapankreatische Erkrankungen wie Mb. Crohn oder Zöliakie. Bei Fehlen morphologischer Läsionen wird die Diagnose durch nicht invasive Tests der exokrinen Pankreasfunktion gesichert. Die Therapie umfasst Enzymsubstitution sowie Nikotin- und Alkohol-Abstinenz. Der Therapieerfolg wird durch klinische oder funktionsdiagnostische Parameter monitiert. Behandlungsziele sind die Normalisierung der Verdauungsfunktion und die Prävention von Gewichtsverlust und Folgeschäden. Bei unzureichendem Ansprechen kann die Dosis der Enzymersatztherapie gesteigert und ein Protonenpumpenhemmer dazu kombiniert werden. </jats:p

Acute Hepatitis Induced by Lyprinol, the Lipid Extract of the Green-Lipped Mussel (Perna canaliculus), in a Patient with Polyarthrosis

Lyprinol, the lipid extract of the green-lipped mussel (Perna canaliculus), is a readily and freely available agent with a putative anti-inflammatory impact. It has already found application as a complementary and supplementary treatment of osteoarthritis, rheumatoid arthritis, asthma, and cancer. So far no major side effects for Lyprinol have been reported, yet. Here, we present the case of a 76-year-old woman with acutely exacerbating abdominal pain and highly elevated liver transaminases while taking Lyprinol as a complementary treatment of polyarthrosis

Intratumoral budding is preoperative biopsies predicts local and distant metastasis in colorectal cancer patients

Objective: In 2011, the term “intratumoral budding, ITB” was used to describe the presence of tumor buds within the main tumor body and was correlated to worse clinical outcome in colorectal cancer patients. Here, we further elucidate the potential clinical role of ITB in pre-operative biopsies using pan-cytokeratin stained tissues and a quantitative scoring system. Method: 139 pre-operative biopsies from patients with colorectal cancer underwent immunohistochemistry for pancytokeratin (AE1/AE3). ITB were counted in the area of densest budding (40×) and classified as high-grade when >10 buds/HPF were observed based on receiver operating characteristic (ROC) curve analysis. Results: High-grade ITB occurred in 26.6 % of cases and was associated with right-sided tumor location (p=0.0356), more advanced pT (p=0.0198) and pN (p<0.0001) classifications, distant metastasis (p=0.0164), higher tumor grade (p=0.0037) and lymphatic invasion (p=0.0445). The specificity and positive predictive value for lymph node metastasis was 86.7 % and 75.6 %, respectively. Disease-free survival was significantly worse in patients with high-grade ITB (5-year survival=25 %) in comparison to patients with low-grade ITB (5-year survival=55 %) (p=0.0157). Conclusion: The assessment of ITB in pre-operative biopsies is predictive of local and distant metastasis in corresponding resections and should be considered in daily management of colorectal cancer patients

Intratumoral budding (ITB) in preoperative biopsies predicts the presence of lymph node and distant metastasis in colon and rectal cancer patients

BACKGROUND: In colorectal cancer (CRC), tumour budding at the invasion front is associated with lymph node (LN) and distant metastasis. Interestingly, tumour budding can also be detected in biopsies (intratumoural budding; ITB) and may have similar clinical importance. Here we investigate whether ITB in preoperative CRC biopsies can be translated into daily diagnostic practice. METHODS: Preoperative biopsies from 133 CRC patients (no neoadjuvant therapy) underwent immunohistochemistry for pan-cytokeratin marker AE1/AE3. Across all biopsies for each patient, the densest region of buds at × 40 (high-power field; HPF) was identified and buds were counted. RESULTS: A greater number of tumour buds in the biopsy was associated with pT stage (P=0.0143), LN metastasis (P=0.0007), lymphatic (P=0.0065) and venous vessel invasion (P=0.0318) and distant metastasis (cM1) (P=0.0013). Using logistic regression, a ‘scale' was developed to estimate the probability of LN and distant metastasis using the number of tumour buds (e.g. 10 buds per HPF: 64% chance of LN metastasis; 30 buds per HPF: 86% chance). Inter-observer agreement for ITB was excellent (intraclass correlation coefficient: 0.813). CONCLUSION: Tumour budding can be assessed in the preoperative biopsy of CRC patients. It is practical, reproducible and predictive of LN and distant metastasis. Intratumoural budding qualifies for further investigation in the prospective setting

Stromal PD-1/PD-L1 Expression Predicts Outcome in Colon Cancer Patients.

INTRODUCTION The programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis plays an important role in controlling immune suppression by down-regulating T effector cell activities, enabling tumor cells to escape from the host's antitumor immunsurveillance. While only a small part of colon cancer cells express PD-L1, we sought to evaluate the differential impact of stromal and epithelial PD-L1 expression of primary tumors and liver metastasis on overall survival (OS) in colon cancer patients. PATIENTS AND METHODS Using a next-generation tissue microarray approach, we assessed both epithelial and stromal PD-L1 expression levels in primary tumors (n = 279) and corresponding liver metastases (n = 14) of colon cancer patients. PD-L1 positivity was graded according to the percentage (0.1%-1%, > 1%, > 5%, > 50%) of tumor cells with membranous PD-L1 expression or as the percentage of positive stroma cells and associated inflammatory infiltrates. We also assessed the interplay between stromal PD-1/PD-L1 and both intratumoral and stromal CD8 count and their impact on outcome. The primary end point was OS. RESULTS Stromal PD-L1 and PD-1 expression were both associated with less aggressive tumor behavior in colon cancer patients, which translated into better OS and disease-free survival, respectively. Conversely, PD-L1 staining in the tumor cells was less frequent than stromal staining and was associated with features of aggressive tumor biology, although without impact on outcome. Interestingly, the PD-L1 staining pattern remained similar between primary tumors and corresponding liver metastases. Stromal PD-1 expression correlated significantly with stromal PD-L1 staining and both intratumoral and stromal CD8 expression. CONCLUSION Stromal PD-1/PD-L1 expression might serve as a prognostic marker in colon cancer patients

TWIST1 and TWIST2 promoter methylation and protein expression in tumor stroma influence the epithelial-mesenchymal transition-like tumor budding phenotype in colorectal cancer.

Tumor budding in colorectal cancer is likened to an epithelial-mesenchymal transition (EMT) characterized predominantly by loss of E-cadherin and up-regulation of E-cadherin repressors like TWIST1 and TWIST2. Here we investigate a possible epigenetic link between TWIST proteins and the tumor budding phenotype. TWIST1 and TWIST2 promoter methylation and protein expression were investigated in six cell lines and further correlated with tumor budding in patient cohort 1 (n = 185). Patient cohort 2 (n = 112) was used to assess prognostic effects. Laser capture microdissection (LCM) of tumor epithelium and stroma from low- and high-grade budding cancers was performed. In colorectal cancers, TWIST1 and TWIST2 expression was essentially restricted to stromal cells. LCM results of a high-grade budding case show positive TWIST1 and TWIST2 stroma and no methylation, while the low-grade budding case was characterized by negative stroma and strong hypermethylation. TWIST1 stromal cell staining was associated with adverse features like more advanced pT (p = 0.0044), lymph node metastasis (p = 0.0301), lymphatic vessel invasion (p = 0.0373), perineural invasion (p = 0.0109) and worse overall survival time (p = 0.0226). Stromal cells may influence tumor budding in colorectal cancers through expression of TWIST1. Hypermethylation of the tumor stroma may represent an alternative mechanism for regulation of TWIST1

CD8/CD45RO T-cell infiltration in endoscopic biopsies of colorectal cancer predicts nodal metastasis and survival

BACKGROUND AND AIMS: Reliable prognostic markers based on biopsy specimens of colorectal cancer (CRC) are currently missing. We hypothesize that assessment of T-cell infiltration in biopsies of CRC may predict patient survival and TNM-stage before surgery. METHODS: Pre-operative biopsies and matched resection specimens from 130 CRC patients treated from 2002-2011 were included in this study. Whole tissue sections of biopsy material and primary tumors were immunostained for pancytokeratin and CD8 or CD45RO. Stromal (s) and intraepithelial (i) T-cell infiltrates were analyzed for prediction of patient survival as well as clinical and pathological TNM-stage of the primary tumor. RESULTS: CD8 T-cell infiltration in the preoperative biopsy was significantly associated with favorable overall survival (CD8i p = 0.0026; CD8s p = 0.0053) in patients with primary CRC independently of TNM-stage and postoperative therapy (HR [CD8i] = 0.55 (95% CI: 0.36-0.82), p = 0.0038; HR [CD8s] = 0.72 (95% CI: 0.57-0.9), p = 0.0049). High numbers of CD8i in the biopsy predicted earlier pT-stage (p < 0.0001) as well as absence of nodal metastasis (p = 0.0015), tumor deposits (p = 0.0117), lymphatic (p = 0.008) and venous invasion (p = 0.0433) in the primary tumor. Infiltration by CD45ROs cells was independently associated with longer survival (HR = 0.76 (95% CI: 0.61-0.96), p = 0.0231) and predicted absence of venous invasion (p = 0.0025). CD8 counts were positively correlated between biopsies and the primary tumor (r = 0.42; p < 0.0001) and were reproducible between observers (ICC [CD8i] = 0.95, ICC [CD8s] = 0.75). For CD45RO, reproducibility was poor to moderate (ICC [CD45i] = 0.16, ICC [CD45s] = 0.49) and correlation with immune infiltration in the primary tumor was fair and non-significant (r[CD45s] = 0.16; p = 0.2864). For both markers, no significant relationship was observed with radiographic T-stage, N-stage or M-stage, indicating that assessment of T-cells in biopsy material can add additional information to clinical staging in the pre-operative setting. CONCLUSIONS: T-cell infiltration in pre-operative biopsy specimens of CRC is an independent favorable prognostic factor and strongly correlates with absence of nodal metastasis in the resection specimen. Quantification of CD8i is highly reproducible and allows superior prediction of clinicopathological features as compared to CD45RO. The assessment of CD8i infiltration in biopsies is recommended for prospective investigation