Protective effect of miR-18a in resected liver metastases of colorectal cancer and FOLFOX treatment.

BACKGROUND: Colorectal cancer ranks second in terms of cancer associated deaths worldwide, whereas miRNA play a pivotal role in the etiology of cancer and its metastases. AIMS: Studying the expression and cellular function of miR-18a in metastatic colorectal cancer and association to progression-free survival. METHODS AND RESULTS: Colorectal liver metastases (N = 123) and primary colorectal cancer (N = 27) where analyzed by RT-PCR and correlated with clinical follow up data. Invasion and migration assays were performed with the liver metastatic cell line LIM2099 after miR-18a knockdown. Cell viability under FOLFOX treatment and knockdown was measured. We found that the expression of miR-18a was increased 4.38-fold in liver metastases and 3.86-fold in colorectal tumor tissue compared to healthy liver tissue and colorectal mucosa, respectively (p ≤ .001). Patients with a high miR-18a expression in liver metastases had a progression-free survival (PFS) of 13.6 months versus 8.9 months in patients with low expression (N = 123; p = .024). In vitro migration of LIM2099 cells was reduced after miR-18a knockdown and cell viability was significantly increased after miR-18a knockdown and treatment with folinic acid or oxaliplatin. Subgroup analysis of PFS revealed significant benefits for patients with high miR-18a expression receiving 5-FU, folinic acid or oxaliplatin. CONCLUSIONS: High expression of miR-18a in colorectal liver metastases might have a protective effect after resection of metastases and FOLFOX treatment regarding PFS.

[(Rare) infectious hepatitis as an important differential diagnosis of unclear hepatopathy]. / (Seltene) infektiöse Hepatitiden als wichtige Differenzialdiagnose der unklaren Hepatopathie.

BACKGROUND: Liver biopsies to determine the cause of unclear hepatopathy and acute liver failure represent a diagnostic hallmark and require close cooperation between clinicians and pathologists. The commonly acute presentation of hepatic dysfunction warrants a rapid diagnosis. Infectious causes of hepatitis may be identified by the pathologist, supporting further diagnostic and therapeutic steps. OBJECTIVES: Rare infectious causes of hepatic dysfunction with distinct histomorphological features are presented. MATERIALS AND METHODS: Retrospective cases of liver biopsies for evaluation of hepatic dysfunction with infection confirmed by laboratory tests were selected from the archive of the institute of pathology of TUM and evaluated for morphologic diagnostic criteria. RESULTS AND CONCLUSIONS: Infections with adenovirus, Herpes simplex virus, Hepatitis A virus, and coxiella burnettii are rare findings in liver core biopsies but able to cause hepatic dysfunction that present with distinct histomorphologic alterations that can contribute to the identification of the causative agent. Rare infectious causes should be considered in any patient presenting with hepatic dysfunction of unknown etiology. Knowledge of the histomorphologic criteria by the pathologist is crucial to initiate further diagnostic testing and treatment.

The Role of Pre-Procurement Pancreas Suitability Score (P-PASS) and Pancreas Donor Risk Index (PDRI) in the Outcome of Simultaneous Pancreas and Kidney or Pancreas After Kidney Transplantation.

BACKGROUND The pre-procurement pancreas suitability score (P-PASS) and the pancreas donor risk index (pDRI) are established predictive scores for graft survival and patient outcome following pancreatic transplantation. This retrospective study aimed to evaluate the predictive value of P-PASS and pDRI following simultaneous pancreas and kidney (SPK) transplantation, or pancreas after kidney (PAK) transplantation, and the clinical impact of donor-specific factors on the postoperative graft and recipient outcome at a single transplant center. MATERIAL AND METHODS The study included 105 patients who underwent SPK (n=104) or PAK (n=4) between 2000 and 2017. Donor-specific and recipient-specific parameters were recorded. Kaplan-Meier analysis and Cox regression analysis were used to assess the outcome after transplantation. RESULTS Overall, the mean 1-year and 5-year pancreas graft survival and patient survival rates were 78.7% and 93.2%, and 76.9% and 90.0%, respectively. The postoperative outcome in patients with a P-PASS score of <17 was not significantly different when compared with patients with a score of ≥17. A P-PASS score of ≥17 was significantly associated with early pancreas graft loss (p=0.04). There was no significant difference in postoperative outcome between patients with high pDRI and low pDRI. Smoking of donor (p=0.046) was a risk factor and coronary heart disease of recipient (p=0.003) had a significant effect on survival of pancreas graft. CONCLUSIONS This study showed that P-PASS and pDRI were not reliable predictors of outcome after pancreas transplantation and that specific characteristics of the donor and recipient must be evaluated when predicting the outcome of pancreas transplantation.