Physical prehabilitation improves the postoperative outcome of associating liver partition and portal vein ligation for staged hepatectomy in experimental model.

Aiming to improve the postoperative outcome of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), the effect of physical prehabilitation (PP) was investigated in experimental model. Male Wistar rats (n = 106) divided to PP and sedentary (S) groups underwent ALPPS. Changes in liver weight, Ki67 index and liver volume by magnetic resonance imaging (MRI) were evaluated. Liver function was assessed by laboratory parameters and 99mTc-mebrofenin single-photon emission computed tomography (SPECT) hepatobiliary scintigraphy (HBS). Utilizing endotoxemia model mortality and septic parameters were investigated. Liver mass (p < 0.001), Ki67 index (p < 0.001) and MRI liver volume (p < 0.05) increased in the PP group compared to the S group. Both standard laboratory parameters (p < 0.001) and HBS (p < 0.05) showed enhanced liver function in the PP group compared to the S group. The vulnerability of animals improved in the PP group, as mortality decreased (p < 0.001), while septic laboratory parameters improved (p < 0.05) compared to the S group in the endotoxemia model. Our study demonstrated for the first time the beneficial role of PP on not only volumetric but also functional liver regeneration and postoperative vulnerability after ALLPS.

Case report of actinomycotic liver abscess following COVID-19 infection.

Introduction and importance: In the last few years, the novel coronavirus, named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), generated a large health care problem worldwide. Due to the immunomodulation effect of the virus the number of opportunistic infections has also increased. Case presentation: We present the unique case of a patient who was diagnosed with an actinomycotic liver abscess after coronavirus disease 2019 (COVID-19) without the presence of any chronic disease or mucosal injury. Clinical discussion: According to the results of the computer tomography (CT scan) and the liver biopsy, the patient was treated with antibiotics and ultrasound-guided drainage. Conclusion: With this case we would like to draw attention to the possible occurrence of liver abscesses caused by an opportunistic pathogen following COVID-19.

The effect of Cyclophilin D depletion on liver regeneration following associating liver partition and portal vein ligation for staged hepatectomy.

AIM: Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) is a modification of two-stage hepatectomy profitable for patients with inoperable hepatic tumors by standard techniques. Unfortunately, initially poor postoperative outcome was associated with ALPPS, in which mitochondrial dysfunction played an essential role. Inhibition of cyclophilins has been already proposed to be efficient as a mitochondrial therapy in liver diseases. To investigate the effect of Cyclophilin D (CypD) depletion on mitochondrial function, biogenesis and liver regeneration following ALPPS a CypD knockout (KO) mice model was created. METHODS: Male wild type (WT) (n = 30) and CypD KO (n = 30) mice underwent ALPPS procedure. Animals were terminated pre-operatively and 24, 48, 72 or 168 h after the operation. Mitochondrial functional studies and proteomic analysis were performed. Regeneration rate and mitotic activity were assessed. RESULTS: The CypD KO group displayed improved mitochondrial function, as both ATP production (P < 0.001) and oxygen consumption (P < 0.05) were increased compared to the WT group. The level of mitochondrial biogenesis coordinator peroxisome proliferator-activated receptor γ co-activator 1-α (PGC1-α) was also elevated in the CypD KO group (P < 0.001), which resulted in the induction of the mitochondrial oxidative phosphorylation system. Liver growth increased in the CypD KO group compared to the WT group (P < 0.001). CONCLUSIONS: Our study demonstrates the beneficial effect of CypD depletion on the mitochondrial vulnerability following ALPPS. Based on our results we propose that CypD inhibition should be further investigated as a possible mitochondrial therapy following ALPPS.

The Role of Farnesoid X Receptor in Accelerated Liver Regeneration in Rats Subjected to ALPPS.

BACKGROUND: the role of bile acid (BA)-induced farnesoid X receptor (Fxr) signaling in liver regeneration following associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) was investigated in a rat model. METHODS: Male Wistar rats underwent portal vein ligation (PVL) (n = 30) or ALPPS (n = 30). Animals were sacrificed pre-operatively and at 24, 48, 72, or 168 h after intervention. Regeneration rate, Ki67 index, hemodynamic changes in the hepatic circulation, and BA levels were assessed. Transcriptome analysis of molecular regulators involved in the Fxr signaling pathway, BA transport, and BA production was performed. RESULTS: ALLPS induced more extensive liver regeneration (p < 0.001) and elevation of systemic and portal BA levels (p < 0.05) than PVL. The mRNA levels of proteins participating in hepatic Fxr signaling were comparable between the intervention groups. More profound activation of the intestinal Fxr pathway was observed 24 h after ALPPS compared to PVL. CONCLUSION: Our study elaborates on a possible linkage between BA-induced Fxr signaling and accelerated liver regeneration induced by ALPPS in rats. ALPPS could trigger liver regeneration via intestinal Fxr signaling cascades instead of hepatic Fxr signaling, thereby deviating from the mechanism of BA-mediated regeneration following one-stage hepatectomy.

Case Report: Morphological Characterization and Long-Term Observation of Bilateral Sequential Internal Mammary Artery Aneurysms in a Patient With Confirmed FBN1 Mutation.

Marfan syndrome (MFS) is a genetically determined connective tissue disorder that leads to ocular, skeletal, and severe cardiovascular involvement. High mortality of MFS is associated with aortic dissection and aneurysm characteristic to the syndrome. In MFS, only a few cases of peripheral arterial involvement have been reported so far, mostly without a genetically confirmed diagnosis. We report a 41-year-old MFS patient with a saccular pearl-string-like aneurysm on the right internal mammary artery (RIMA) and a single aneurysm on the left internal mammary artery (LIMA). To our knowledge this is the first reported case on internal mammary artery aneurysms with this special morphology and with follow-up and blood pressure control as primary therapeutic approach in a patient with genetically confirmed MFS. The aneurysms with the above described morphology first appeared as small aneurysms on a CT scan 6 years after a cardiac operation. Due to the lack of guidelines, based on the asymptomatic state of the patient, the increased tortuosity of the affected vessels and the history of prior cardiac surgery, we decided to closely monitor these aneurysms with blood pressure control and without carrying out any interventions. On the CT scans done 3, 11, 12, 17, and 32 months after identifying the aneurysms, no progression of these structures was detected. Our findings confirm the possibility of the occurrence of internal mammary artery aneurysms in patients with FBN1 mutation and we believe that monitoring these aneurysms with blood pressure management can be a suitable option in selected cases.

The effects of physical prehabilitation: Improved liver regeneration and mitochondrial function after ALPPS operation in a rodent model.

BACKGROUND: To identify the role of physical prehabilitation (PP) in liver regeneration, mitochondrial function, biogenesis, and inflammatory response was investigated after associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in a rodent model. METHODS: Male Wistar rats (n = 60) underwent ALPPS. Animals were divided (n = 30) to the physical prehabilitation group (PP) and sedentary group (S). The animals were exsanguinated before (0 hour) and 24, 48, 72, or 168 hours after the operation. Regeneration rate and proliferation index were assessed. Mitochondrial function, biogenesis, and inflammatory response were evaluated. RESULTS: Regeneration rate and Ki67 index were significantly increased in the PP group compared to the S group (P < .001). Due to the changes in oxidative capacity and ATP production rate, the P/O ratio of PP group compared to the S group was significantly increased (P < .05). PP group was characterized by accelerated mitochondrial biogenesis and less intense inflammatory response compared to the S group. CONCLUSIONS: To our knowledge, this is the first demonstration of the beneficial effects of PP on liver regeneration, mitochondrial function, biogenesis, and the inflammatory response after ALPPS.

Increased visceral arterial tortuosity in Marfan syndrome.

BACKGROUND: Clinical evidence suggests that the currently recommended approach to estimate the risk of aortic dissection in Marfan syndrome (MFS) is not reliable enough. Therefore, we investigated the possible role of visceral arterial tortuosity in the risk stratification. METHODS AND RESULTS: Splenic and renal arteries of 37 MFS patients and 74 age and gender matched control subjects were segmented using CT angiography imaging. To measure tortuosity, distance metric (DM), sum of angles metric (SOAM), inflection count metric (ICM), and the ratio of ICM and SOAM (ICM/SOAM) were calculated. DM of the splenic, right and left renal artery was significantly higher in MFS patients than in controls (2.44 [1.92-2.80] vs. 1.75 [1.57-2.18] p < 0.001; 1.16 [1.10-1.28] vs. 1.11 [1.07-1.15] p = 0.011; 1.40 [1.29-1.70] vs. 1.13 [1.09-1.23] p < 0.001, respectively). A similar tendency for ICM and an opposite tendency for SOAM were observed. ICM/SOAM was significantly higher in the MFS group compared to controls in case of all three arteries (73.35 [62.26-93.63] vs. 50.91 [43.19-65.62] p < 0.001; 26.52 [20.69-30.24] vs. 19.95 [16.47-22.95] p < 0.001; 22.81 [18.64-30.96] vs. 18.38 [15.29-21.46] p < 0.001, respectively). MFS patients who underwent aortic root replacement had increased right and left renal DM and ICM/SOAM compared to MFS patients without surgery. CONCLUSION: To our knowledge this is the first demonstration of increased arterial tortuosity in MFS on visceral arteries. Visceral arterial tortuosity, dominated by curves of lower frequency but higher amplitude according to the observed opposite tendency between the DM and SOAM metrics, could be a possible new predictor of serious manifestations of MFS.

Hungarian Marfan family with large FBN1 deletion calls attention to copy number variation detection in the current NGS era.

Copy number variations (CNVs) comprise about 10% of reported disease-causing mutations in Mendelian disorders. Nevertheless, pathogenic CNVs may have been under-detected due to the lack or insufficient use of appropriate detection methods. In this report, on the example of the diagnostic odyssey of a patient with Marfan syndrome (MFS) harboring a hitherto unreported 32-kb FBN1 deletion, we highlight the need for and the feasibility of testing for CNVs (>1 kb) in Mendelian disorders in the current next-generation sequencing (NGS) era.