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Purpose: Bilateral native nephrectomies are needed in ESRD patients with select indications in a pre-transplant setting. Yet, the perioperative morbidity is significant in this population. Herein we evaluate the efficacy and utility of r-SABN., Method: A total of 12 patients were consented at a single center. Of 12 patients, 3 patients did not meet study criteria and were excluded. Preoperative, perioperative, and postoperative data were prospectively collected from 9 patients from electronic health records and administered postoperative surveys. Patients were assessed at 30-180 days postoperatively for follow-up., Results: Mean operative time was 204.3 ± 59.7 min (142.0-314.0) and estimated blood loss during operation was 94.4 ± 87.3 ml (25.0-300.0). The mean length of hospital stay was 2 ± 0.7 days (1-3) for all patients. Total post-operative opioid usage was normalized to morphine dose equivalents (MDE) and calculated to be 56.1 ± 30.4 mg (30.8-101.8). Patients experienced a fourfold and tenfold respective increase in weekly structural and incidental physical activity from 30 to 180 days postoperatively. There were no procedure related intraoperative or postoperative complications reported in the cohort., Conclusion: Overall, r-SABN afforded the patients low morbidity. Longitudinal studies are in progress to further assess the efficacy and outcome of this procedure. In a single-center study, we demonstrate r-SABN is viable and provides a novel tool for treatment of ESRD patients requiring this procedure., (© 2020. Springer-Verlag London Ltd., part of Springer Nature.)

Precision medicine with genetic profiling of tumor tissue has become an essential part of routine clinical practice in colorectal cancer. However, tissue genetic profiling suffers from clonal evolution, tumor heterogeneity, and time needed to deliver critical information for prompt clinical decision making. In contrast, liquid biopsy with plasma circulating tumor DNA provides genetic and epigenetic information from both the primary and metastatic colorectal cancer, which can potentially capture tumor heterogeneity and evolution with time and treatment. In addition, liquid biopsy with circulating tumor DNA is minimally invasive, quicker, and easily repeatable with high patient compliance to provide both qualitative and quantitative molecular information in real-time. We provide an overview on the potential clinical applications of circulating tumor DNA in the screening, surveillance, and treatment monitoring of colorectal cancer.

Purpose: In patients with loin pain hematuria syndrome (LPHS), a response to percutaneous renal hilar blockade (RHB) and a multidisciplinary team (MDT) evaluation predicts patient's potential renal auto-transplantation (RAT) success., Methods: A pain assessment was performed using a 0-10 numeric pain rating scale prior to a percutaneous RHB under CT guidance. If the pain score was reduced > 50% immediately after the RHB, patients were evaluated for RAT by a MDT. Pre-operative and 1-year post-operative quality-of-life surveys were administered to each RAT patient., Results: 43 LPHS patients were referred for RHB. Of the 38 patients who received a RHB, 31 had > 50% reduction in pain scores. Pre- and post-RHB mean pain scores were 6/10 and 0.7/10, respectively, in patients who had > 50% reduction in pain. 22 of the patients who responded favorably then proceeded to RAT. Twelve patients had at least 1-year follow-up after RAT. All patients had a meaningful decrease in their pain. Mean pain score at 1 year was 0.8/10 for an 85% overall reduction in pain. 92% of patients experienced a ≥ 50% reduction in pain at 1 year. Mean Beck Depression Inventory (BDI) score (0-66) 1 year after RAT decreased from 25.2 pre-op (moderate depression) to 12.8 post-op (minimal depression)., Conclusions: A MDT approach utilizing a RHB should be considered as a tool to select appropriate LPHS patients for RAT to achieve long-term success in reducing chronic pain and depression while increasing quality of life.

Background: Local hemostatic agents have a role in limiting bleeding complications associated with liver resection., Methods: In this randomized, phase III study, we compared the efficacy and safety of Fibrin Sealant Grifols (FS Grifols) with oxidized cellulose sheets (Surgicel®) as adjuncts to hemostasis during hepatic resections. The primary efficacy endpoint was the proportion of patients achieving hemostasis at target bleeding sites (TBS) within 4 min (T 4 ) of treatment application. Secondary efficacy variables were time to hemostasis (TTH) at a later time point if re-bleeding occurs and cumulative proportion of patients achieving hemostasis by time points T 2 , T 3 , T 5 , T 7 , and T 10 ., Results: The rate of hemostasis by T 4 was 92.8% in the FS Grifols group (n = 163) and 80.5% in the Surgicel® group (n = 162) (p = 0.01). The mean TTH was significantly shorter (p < 0.001) in the FS Grifols group (2.8 ± 0.14 vs. 3.8 ± 0.24 min). The rate of hemostasis by T 2 , T 5 , and T 7 was higher and statistically superior in the FS Grifols group compared to Surgicel®. No substantial differences in adverse events (AE) were noted between treatment groups. The most common AEs were procedural pain (36.2 vs. 37.7%), nausea (20.9 vs. 23.5%), and hypotension (14.1 vs 6.2%)., Conclusions: FS Grifols was safe and well tolerated as a local hemostatic agent during liver resection surgeries. Overall, data demonstrate that the hemostatic efficacy of FS Grifols is superior to Surgicel® and support the use of FS Grifols as an effective local hemostatic agent in these surgical procedures.

Management of hepatocellular carcinoma in the early cirrhotic remains controversial. The exact role of liver transplantation versus resection remains to be determined. The following short review attempts to present the evidence for the respective roles of liver transplantation versus liver resection in early stage HCC.

Background: Surgical resection and liver transplantation remain the only treatments that offer cure for hepatoma, but are limited to those with early stage disease. Prelisting radiological staging is not always definitive. In this study, we sought to delineate the role of laparoscopy for clarification of staging in advanced cirrhotic patients when radiological assessment during evaluation for orthotopic liver transplants (OLTx) is equivocal., Methods: Over a 3-year period, 18 patients with advanced liver insufficiency being evaluated for OLTx listing underwent laparoscopic staging when the following criteria were met: (1) lesion(s) with indeterminate size/borders, (2) an indeterminate number of lesions, or (3) lesion(s) and alpha-fero protein (AFP) less than 100 ng/ml. Patients underwent exploratory laparoscopy and laparoscopic ultrasound with biopsy, with or without ablation of lesion(s)., Results: Laparoscopic staging was initiated in 18 patients; four of the first six patients were converted to open procedures. Twelve patients were restaged as a result of the procedure: six down-staged and six up-staged. Stage changes were based on laparoscopic visualization of advanced disease in two, ultrasonographic clarification of tumor size/number in seven, and biopsy in three. Twelve of the 14 laparoscopic procedures included laparoscopic radiofrequency ablation while one received ethanol ablation. One patient required 2 units of red blood cells. One patient died on postoperative day 7 because of gastrointestinal bleeding. Four of the six down-staged patients underwent liver transplant, and pathological staging of the explants agreed with laparoscopic staging in all cases., Conclusion: Laparoscopic staging for HCC in advanced cirrhosis can clearly characterize tumor burden when preoperative radiological assessment is equivocal.

Because tumor necrosis factor-alpha (TNF-alpha) and some chemotherapeutic agents activate both apoptosis and NF-kappaB-dependent antiapoptotic genes, they may neutralize their own antitumor effects. The cell-signaling mechanisms for such chemoresistance are not clear but may involve phosphotidylinositol-3' kinase (PI3K). To clarify this we examined whether cross-signaling between PI3K and NF-kappaB enhances the antitumor effect of TNF-alpha in human pancreatic cancer cells. Quiescent pancreatic cancer cells (Panc-1, MiaPaCa-2) with TNF-alpha, Ly294002 (PI3K inhibitor), alone or combined, were restimulated with mitogen (10% fetal calf serum [FCS] to induce cell cycle entry). Proliferation (monotetrazolium), cell cycle progression (ApoBrDU and fluorescence-activated cell sorter analysis), and apoptosis (PARP cleavage; caspase-3 activation) were measured. Akt activation (Akt kinase assay) and IkappaBalpha degradation were determined by Western blot analysis. Translocation of NF-kappaB into the nucleus was examined by EMSA, whereas an NF-kappaB/luciferase reporter gene was used to quantify NF-kappaB-dependent gene expression. Statistical analysis was carried out by means of two-tailed t test (P <0.05). PI3K inhibition significantly enhanced the antiproliferative and proapoptotic effects of TNF-alpha in both cell lines, Ly294002 also blocked TNF-alpha-induced Akt activation but failed to alter cytoplasmic IkappaBalpha degradation or subsequent NF-kappaB nuclear translocation. NF-kappaB-dependent gene expression, however, was ultimately suppressed by Ly294002, suggesting that PI3k-dependent activation of NF-kappaB is IkappaBalpha independent. PI3K inhibition can block NF-kappaB-dependent gene expression regardless of cytoplasmic IkappaBalpha/NF-kappaB activation. Because it also regulates the antitumor effects of TNF-alpha, PI3K may in part determine NF-kappaB-induced chemoresistance in human pancreatic cancer.

Although hypoosmotic stress-induced cell swelling activates phosphatidylinositol-3-kinase, its impact on the downstream signal protein kinase B and cell growth is unknown. Activator protein-1 is in part phosphatidylinositol-3-kinase dependent, and is important in proliferation. We hypothesized that cell swelling modulates proliferation in HepG2 cells via the protein kinase B-dependent activation of activator protein-1. HepG2 cells pretreated with or without LY294002 were exposed for up to 30 minutes to hypoosmotic medium (160 mOsm/L). Tumor necrosis factor-alpha (1.4 nmol/L) or normoosmolar medium (270 mOsm/L) served as positive and negative controls, respectively. Western immunoblots measured cytoplasmic phosphorylated and total protein kinase B. Electromobility shift assays measured nuclear activator protein-1. Methylene blue assays measured cell proliferation at 24, 48, and 72 hours after stimulation. Hypoosmotic stress phosphorylated protein kinase B by 10 minutes. Subsequently, hypoosmotic exposure stimulated activator protein-1 by 30 minutes. Pulse exposure to hypoosmotic stress potentiated HepG2 proliferation by 72 hours as compared to both negative controls and LY-inhibited cells (n = 4 per group, P = 0.009 and P = 0.004, respectively; P <0.001 analysis of variance. All three activation events were abolished with LY294002 pretreatment. In HepG2 cells, hypoosmotic stress-induced swelling stimulates proliferation via protein kinase B-mediated activation of activator protein-1. These data delineate a possible mechanism linking changes in cell volume to growth in human liver cancer.

Hemodynamic properties of a donor liver, during initial reperfusion, are associated with the degree of graft preservation injury and have been proposed to correlate with subsequent markers of liver function. In the present study, hepatic hemodynamics, that is, portal venous pressure, hepatic vascular resistance, and compliance (vascular distensibility), were characterized (1) in situ before porcine livers were manipulated, (2) after these same livers were isolated and perfused within a bypass circuit, and (3) on reperfusion after 2 hours of cold ischemia. Hepatic vascular resistance was determined in each of these three states from the portal vein pressure response to differing hepatic blood flows. In addition, the response of the same livers to norepinephrine and nitroprusside was evaluated in each condition. In the in situ and isolated perfused liver, portal venous pressure increased only modestly despite doubling of hepatic flows. After cold ischemia, the pressure response to higher flows was significantly greater and much less of a reduction in hepatic vascular resistance was noted than in studies prior to cold ischemia. Unlike livers prior to cold ischemia, the pressure response to norepinephrine was attenuated following cold ischemia. The response to nitroprusside, however, remained intact reducing the portal pressure to that of in situ livers. Therefore the portal hypertension that follows cold ischemia appears to be largely provoked by the preservation injury and not by surgical manipulation or the bypass circuit. This increment in portal pressure is responsive to a nitric oxide donor.