No transhepatic gradient of bDNA was evident, suggesting that no major hepatic elimination of bDNA occurs in advanced liver disease. bDNA, in contrast to previous reports was largely unrelated to a panel of markers of inflammation and without relation to portal pressure.
BackgroundGastrointestinal dysmotility may be involved in the development of bacterial translocation and infection in patients with liver cirrhosis. The aim of the present study was to describe gastric, small intestinal and colorectal motility and transit in patients with liver cirrhosis and portal hypertension using a magnet-based Motility Tracking System (MTS-1) and standard radiopaque markers.MethodsWe included 15 patients with liver cirrhosis (8 Child-Pugh A, 6 Child-Pugh B, and 1 Child-Pugh C) and portal hypertension (11 males, median age 54 years (range 38–73), median hepatic venous pressure gradient 18 mmHg (range 12–37)), and 18 healthy controls (8 males, median age 58 years (range 34–64)). The gastric emptying time and small intestinal motility were evaluated by MTS-1, and the total gastrointestinal transit time was assessed by radiopaque markers and abdominal radiographs.ResultsThe velocity through the proximal small intestine was significantly higher in cirrhotic patients (median 1.27 metres (m)/hour, range 0.82–2.68) than in the healthy controls (median 1.00 m/hour, range 0.46–1.88) (p = 0.03). Likewise, the magnet travelled significantly longer in both fast (p = 0.04) and slow movements (p = 0.05) in the patient group. There was no significant difference in either gastric emptying time—23 minutes (range 5–131) in patients and 29 minutes (range 10.5–182) in healthy controls (p = 0.43)—or total gastrointestinal transit time—1.6 days (range 0.5–2.9) in patients and 2.0 days (range 1.0–3.9) in healthy controls (p = 0.33). No correlation was observed between the hepatic venous pressure gradient and the velocity of the magnet through the small intestine.ConclusionPatients with liver cirrhosis and portal hypertension demonstrated faster-than-normal transit through the proximal small intestine. This may be due to an overactive bowel, as suggested by previous studies.
This study showed hepatic soluble mannose receptor excretion with a higher level in the hepatic than the portal vein, though with no associations to bacterial DNA. We observed associations between soluble mannose receptor levels and portal pressure and higher levels in patients with acute variceal bleeding indicating the soluble mannose receptor as a marker of complications of cirrhosis, but not bacterial translocation.
Background and aims
Studies suggest that mutations in the CTNNB1 gene are predictive of response to immunotherapy, an emerging therapy for advanced hepatocellular carcinoma (HCC). Analysis of circulating tumor DNA (ctDNA) offers the possibility of serial non-invasive mutational profiling of tumors. Combining tumor tissue and ctDNA analysis may increase the detection rate of mutations.
This study aimed to evaluate the frequency of the CTNNB1 p.T41A mutation in ctDNA and tumor samples from HCC patients and to evaluate the concordance rates between plasma and tissue. We further evaluated changes in ctDNA after various HCC treatment modalities and the impact of the CTNNB1 p.T41A mutation on the clinical course of HCC.
Methods
We used droplet digital PCR to analyze plasma from 95 patients and the corresponding tumor samples from 37 patients during 3 years follow up.
Results
In tumor tissue samples, the mutation rate was 8.1% (3/37). In ctDNA from HCC patients, the CTNNB1 mutation rate was 9.5% (9/95) in the pre-treatment samples. Adding results from plasma analysis to the subgroup of patients with available tissue samples, the mutation detection rate increased to 13.5% (5/37). There was no difference in overall survival according to CTNNB1 mutational status. Serial testing of ctDNA suggested a possible clonal evolution of HCC or arising multicentric tumors with separate genetic profiles in individual patients.
Conclusion
Combining analysis of ctDNA and tumor tissue increased the detection rate of CTNNB1 mutation in HCC patients. A liquid biopsy approach may be useful in a tailored therapy of HCC.
Background: Neuroendocrine tumors (NETs) are rare and characterized by a heterogeneous clinical course and an unmet need for better prognostic markers. Plasma cell-free DNA (cfDNA) has prognostic value in other malignancies but is not previously investigated in NETs. We studied cfDNA levels in patients with mainly low grade small intestinal (siNET) or pancreatic NET (pNET) and evaluated the prognostic potential of cfDNA.
Material and methods: We included 70 NET patients, siNET(n=50) and pNET(n=20). Plasma cfDNA levels were determined by droplet digital PCR for the Beta-2-microglobulin gene every six months during a period of three years, including in a subgroup of 19 patients during Peptide Receptor Radionuclide Therapy (PRRT) therapy.
Results: CfDNA levels were higher in both siNET and pNET compared to a previously established healthy cohort (p<0.0001). cfDNA levels did not predict overall survival (crude HR 0.95 (0.57-1.58), p=0.837, adjusted for smoking status HR 0.77 (0.51-1.17), p=0.22). The impact of cfDNA level on progression-free survival showed different trends in siNET and pNET. There was no effect of PRRT treatment on cfDNA levels and no difference in cfDNA levels between patients with and without progressive disease after PRRT (ANOVA p=0.66). CfDNA levels were significantly higher in never-smokers and previous smokers than in current smokers (p=0.029).
Conclusion: cfDNA levels are higher in NET patients than in healthy controls, however, there was no association with prognosis, and cfDNA levels were unaffected by PRRT. Our observations suggest that cfDNA levels are not associated with the disease course in low-grade NET in contrast to other malignancies.
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