Introduction
Since the early SARS-CoV-2 pandemic, cancer patients have been assumed to be at higher risk for severe COVID-19. Here, we present an analysis of cancer patients from the LEOSS (Lean ...European Open Survey on SARS-CoV-2 Infected Patients) registry to determine whether cancer patients are at higher risk.
Patients and methods
We retrospectively analyzed a cohort of 435 cancer patients and 2636 non-cancer patients with confirmed SARS-CoV-2 infection, enrolled between March 16 and August 31, 2020. Data on socio-demographics, comorbidities, cancer-related features and infection course were collected. Age-, sex- and comorbidity-adjusted analysis was performed. Primary endpoint was COVID-19-related mortality.
Results
In total, 435 cancer patients were included in our analysis. Commonest age category was 76–85 years (36.5%), and 40.5% were female. Solid tumors were seen in 59% and lymphoma and leukemia in 17.5% and 11% of patients. Of these, 54% had an active malignancy, and 22% had recently received anti-cancer treatments. At detection of SARS-CoV-2, the majority (62.5%) presented with mild symptoms. Progression to severe COVID-19 was seen in 55% and ICU admission in 27.5%. COVID-19-related mortality rate was 22.5%. Male sex, advanced age, and active malignancy were associated with higher death rates. Comparing cancer and non-cancer patients, age distribution and comorbidity differed significantly, as did mortality (14% vs 22.5%,
p
value < 0.001). After adjustments for other risk factors, mortality was comparable.
Conclusion
Comparing cancer and non-cancer patients, outcome of COVID-19 was comparable after adjusting for age, sex, and comorbidity. However, our results emphasize that cancer patients as a group are at higher risk due to advanced age and pre-existing conditions.
Hepatic recurrence of liver malignancies is a leading problem in patients after liver resection with curative intention. Thermoablation is a promising treatment approach for patients after hepatic ...resection, especially in liver-limited conditions. This study aimed to investigate safety, survival, and local tumor control rates of MRI-guided percutaneous thermoablation of recurrent hepatic malignancies following hepatic resection.
Data from patients with primary or secondary hepatic malignancies treated between 2004 and 2018 with MRI-guided percutaneous thermoablation of hepatic recurrence after prior hepatic resection were retrospectively analyzed. Disease-free survival and overall survival rates were calculated using the Kaplan-Meier method.
A total of 57 patients with hepatic recurrence (mean tumor size = 18.9 ± 9.1 mm) of colorectal cancer liver metastases (n = 27), hepatocellular carcinoma (n = 17), intrahepatic recurrence of cholangiocellular carcinoma (n = 9), or other primary malignant tumor entities (n = 4) were treated once or several times with MR-guided percutaneous radiofrequency (n = 52) or microwave ablation (n = 5) (range: 1-4 times). Disease progression occurred due to local recurrence at the ablation site in nine patients (15.8%), non-local hepatic recurrence in 33 patients (57.9%), and distant malignancy in 18 patients (31.6%). The median overall survival for the total cohort was 40 months and 49 months for the colorectal cancer group, with a 5-year overall survival rate of 40.7 and 42.5%, respectively. The median disease-free survival was 10 months for both the total cohort and the colorectal cancer group with a 5-year disease-free survival rate of 15.1 and 14.8%, respectively. The mean follow-up time was 39.6 ± 35.7 months.
MR-guided thermoablation is an effective and safe approach in the treatment of hepatic recurrences in liver-limited conditions and can achieve long-term survival.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The ALPSS procedure has been recently introduced as an alternative to PVE for liver volume augmentation in cases of planned right trisectionectomy with small future RLV and high risk of PHLF. We ...retrospectively analysed our single centre experience with 15 ALPPS procedures in order to better assess the limits and indications of the procedure.
The following volumetric parameters were evaluated: total liver volume (TLV), remnant liver volume (RLV), remnant liver volume to total liver volume ratio (RLV/TLV), remnant liver volume to body weight ratio (RLV/BWR) and median volume gain. The ALPPS procedure was usually considered when RLV/TLV < 25 % or RLV/BWR < 0.5. The ALPPS procedure consisted of phase 1 (in situ splitting of the liver), interphase (waiting for liver regeneration) and phase 2 (completion of right trisectionectomy). Postoperative complications were reported according to the Dindo-Clavien classification. Patient survival, late complications and tumour recurrence were analysed.
Between November 2010 and September 2013, we performed 15 ALPPS procedures in 10 patients with primary liver tumours (5 h-CCA, 4 i-CCA and 1 HCC) and in 5 with CRLM. The preoperative RLV/TLV ratio was 22.6 % (15.7 - 29.2) and the RLV/BWR 0.46 (0.22 - 0.66). After 10 days (range 8 - 16) the RLV/TLV ratio and RLV/BWR increased up to 36.3 % (30 - 59.2 %) and 0.67 (0.5 - 1.2) respectively, with a median volume gain of 87.2 % (23.8 - 161 %). The time interval between phases 1 and 2 was 13 days (9 - 18). An R0 status was reached in 13 patients and R1 in 2. The overall postoperative morbidity was 66.7 %. After phase 1, 8 patients experienced 19 complications and 7 none. After phase 2, 11 patients experienced 36 complications and 4 none. Four patients died postoperatively after 22 days (9 - 36 days) resulting in a postoperative mortality of 28.7 %. After a median follow-up of 17 months (1 - 33), 10 out of 15 patients are still alive (survival rate 66.6 %). Four patients (2 i-CCA, 1 CRLM, 1 HCC) developed tumour recurrences (2 intrahepatic and 2 extrahepatic). One patient with i-CCA died at POM 4 secondary to peritoneal carcinosis.
The actual high morbidity and mortality rates related to the ALPPS procedure should lead us to a more cautious selection of the candidates for this operation and restriction of the indications through an accurate work-up based on interdisciplinary cooperation among hepatologists, oncologists, radiologists and surgeons.
Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD) and a lead indication for liver transplantation (LT) in the western world. In ...this article, we present a Consensus Statement on LT practice, developed by a dedicated Guidelines’ Taskforce of the European Society of Organ Transplantation (ESOT). The overarching goal is to provide practical guidance on commonly debated topics, including indications and timing of LT, management of bile duct stenosis in patients on the transplant waiting list, technical aspects of transplantation, immunosuppressive strategies post-transplant, timing and extension of intestinal resection and futility criteria for re-transplantation.
Renal sinus fat (RSF) is a perivascular fat compartment located around renal arteries. In this in vitro and in vivo study we hypothesized that the hepatokine fetuin-A may impair renal function in ...non alcoholic fatty liver disease (NAFLD) by altering inflammatory signalling in RSF. To study effects of the crosstalk between fetuin-A, RSF and kidney, human renal sinus fat cells (RSFC) were isolated and cocultured with human endothelial cells (EC) or podocytes (PO). RSFC caused downregulation of proinflammatory and upregulation of regenerative factors in cocultured EC and PO, indicating a protective influence of RFSC. However, fetuin-A inverted these benign effects of RSFC from an anti- to a proinflammatory status. RSF was quantified by magnetic resonance imaging and liver fat content by
H-MR spectroscopy in 449 individuals at risk for type 2 diabetes. Impaired renal function was determined via urinary albumin/creatinine-ratio (uACR). RSF did not correlate with uACR in subjects without NAFLD (n = 212, p = 0.94), but correlated positively in subjects with NAFLD (n = 105, p = 0.0005). Estimated glomerular filtration rate (eGRF) was inversely correlated with RSF, suggesting lower eGFR for subjects with higher RSF (r = 0.24, p < 0.0001). In conclusion, our data suggest that in the presence of NAFLD elevated fetuin-A levels may impair renal function by RSF-induced proinflammatory signalling in glomerular cells.
Posttransplant immunosuppression with calcineurin inhibitors (CNIs) is associated with impaired renal function, while mTor inhibitors such as everolimus may provide a renal‐sparing alternative. In ...this randomized 1‐year study in patients with liver transplantation (LTx), we sought to assess the effects of everolimus on glomerular filtration rate (GFR) after conversion from CNIs compared to continued CNI treatment. Eligible study patients received basiliximab induction, CNI with/without corticosteroids for 4 weeks post‐LTx, and were then randomized (if GFR > 50 mL/min) to continued CNIs (N = 102) or subsequent conversion to EVR (N = 101). Mean calculated GFR 11 months postrandomization (ITT population) revealed no significant difference between treatments using the Cockcroft‐Gault formula (−2.9 mL/min in favor of EVR, 95%‐CI: −10.659; 4.814, p = 0.46), whereas use of the MDRD formula showed superiority for EVR (−7.8 mL/min, 95%‐CI: −14.366; −1.191, p = 0.021). Rates of mortality (EVR: 4.2% vs. CNI: 4.1%), biopsy‐proven acute rejection (17.7% vs. 15.3%), and efficacy failure (20.8% vs. 20.4%) were similar. Infections, leukocytopenia, hyperlipidemia and treatment discontinuations occurred more frequently in the EVR group. No hepatic artery thrombosis and no excess of wound healing impairment were noted. Conversion from CNI‐based to EVR‐based immunosuppression proved to be a safe alternative post‐LTx that deserves further investigation in terms of nephroprotection.
Results from the PROTECT randomized phase II clinical study of liver transplant recipients with good renal function show that the switch from a calcineurin inhibitor to everolimus provides a benefit for renal function after one year.
Primary human hepatocytes (PHH) are the “gold standard” for in vitro toxicity tests. However, 2D PHH cultures have limitations that are due to a time-dependent dedifferentiation process visible by ...morphological changes closely connected to a decline of albumin production and CYP450 activity. The 3D in vitro culture corresponds to in vivo-like tissue architecture, which preserves functional characteristics of hepatocytes, and therefore can at least partially overcome the restrictions of 2D cultures. Consequently, several drug toxicities observed in vivo cannot be reproduced in 2D in vitro models, for example, the toxic effects of acetaminophen. The objective of this study was to identify molecular differences between 2D and 3D cultivation which explain the observed toxicity response. Our data demonstrated an increase in cell death after treatment with acetaminophen in 3D, but not in 2D cultures. Additionally, an acetaminophen concentration-dependent increase in the CYP2E1 expression level in 3D cultures was detected. However, during the treatment with 10 mM acetaminophen, the expression level of SOD gradually decreased in 3D cultures and was undetectable after 24 h. In line with these findings, we observed higher import/export rates in the membrane transport protein, multidrug resistance-associated protein-1, which is known to be specific for acetaminophen transport. The presented data demonstrate that PHH cultured in 3D preserve certain metabolic functions. Therefore, they have closer resemblance to the in vivo situation than PHH in 2D cultures. In consequence, 3D cultures will allow for a more accurate hepatotoxicity prediction in in vitro models in the future.
Objective
The venous vascular anatomy of the caudate lobe is exceptional. The purpose of this study was to assess portal inflow and venous outflow volumes of the caudate lobe.
Methods
Extrahepatic ...(provided by the first-order branches) versus intrahepatic (provided by the second- to third-order branches) portal inflow, as well as direct (via Spieghel veins) versus indirect (via hepatic veins) venous drainage patterns were analyzed in virtual 3-D liver maps in 140 potential live liver donors.
Results
The caudate lobe has a greater intrahepatic than extrahepatic portal inflow volume (mean 55 ± 26 vs. 45 ± 26%:
p
= 0.0763), and a greater extrahepatic than intrahepatic venous drainage (mean 54–61 vs. 39–46%). Intrahepatic drainage based on mean estimated values showed the following distribution: middle > inferior (accessory) > right > left hepatic vein.
Conclusions
Sacrifice of extrahepatic caudate portal branches can be compensated by the intrahepatic portal supply. The dominant outflow via Spieghel veins and the negligible role of left hepatic vein in caudate venous drainage may suggest reconstruction of caudate outflow via Spieghel veins in instances of extended left hemiliver live donation not inclusive of the middle hepatic vein. The anatomical data and the real implication for living donors must be further verified by clinical studies.
The feasibility of de novo everolimus without calcineurin inhibitor (CNI) therapy following liver transplantation was assessed in a multicenter, prospective, open‐label trial. Liver transplant ...patients were randomized at 4 weeks to start everolimus and discontinue CNI, or continue their current CNI‐based regimen. The primary endpoint was adjusted estimated GFR (eGFR; Cockcroft‐Gault) at month 11 postrandomization. A 24‐month extension phase followed 81/114 (71.1%) of eligible patients to month 35 postrandomization. The adjusted mean eGFR benefit from randomization to month 35 was 10.1 mL/min (95% confidence interval CI −1.3, 21.5 mL/min, p = 0.082) in favor of CNI‐free versus CNI using Cockcroft‐Gault, 9.4 mL/min/1.73 m2 (95% CI −0.4, 18.9, p = 0.053) with Modification of Diet in Renal Disease (four‐variable) and 9.5 mL/min/1.73 m2 (95% CI −1.1, 17.9, p = 0.028) using Nankivell. The difference in favor of the CNI‐free regimen increased gradually over time due to a small progressive decline in eGFR in the CNI cohort despite a reduction in CNI exposure. Biopsy‐proven acute rejection, graft loss and death were similar between groups. Adverse events led to study drug discontinuation in five CNI‐free patients and five CNI patients (12.2% vs. 12.5%, p = 1.000) during the extension phase. Everolimus‐based CNI‐free immunosuppression is feasible following liver transplantation and patients benefit from sustained preservation of renal function versus patients on CNI for at least 3 years.
The beneficial effect on renal function achieved by early CNI withdrawal and treatment with everolimus after liver transplantation is still evident after three years.
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