Can living donor liver transplantation provide similar outcomes to deceased-donor liver transplantation for hepatocellular carcinoma? A systematic review and meta-analysis.

BACKGROUND AND AIM: A potential solution to the deceased organ shortage is to include live organ donations and to identify patients with lower rates of HCC recurrence to fairly allocate liver grafts. Our aims were to detect the long-term outcomes of LDLT versus DDLT for HCC and predictors of recurrence after transplantation. METHODS: PubMed, Scopus, Web of Science, Cochrane library were searched for eligible studies from inception to July 2021 and a systematic review and meta-analysis were done. RESULTS: 35 studies with a total of 7822 patients were included. The 1-, 3-, 4 year-OS showed trivial improvement for LDLT recipients. However, the two modalities had similar 5-, 6- and 10-year OS. A significant improvement in the ITT-OS was observed for LDLT recipients. Regarding the DFS and recurrence after transplantation, no significant difference was observed between LDLT and DDLT. In addition to that, the pooled hazard ratio of the included studies showed that Milan criteria, level of AFP, presence of vascular invasion, tumor differentiation were significant predictors of recurrence. CONCLUSION: The cancer biology (not the graft type) is the most important determinant of recurrence and survival after LT. However, LDLT provided much better survival benefits to HCC patients especially in regions that suffer from low deceased organ availability.

Effect of norepinephrine on blood volume, cardiac output, and systemic filling pressure in patients undergoing liver transplantation.

BACKGROUND: Patients with liver cirrhosis develop symptoms comparable to those of patients with sepsis, who have increased total vascular compliance, which may cause blood pooling in the venous pool. No previous studies have evaluated the effect of using norepinephrine on the intravascular blood volume. We investigated the norepinephrine infusion's effect on the mean systemic filling pressure, venous return, and cardiac preload in patients undergoing liver transplantation. METHODS: Overall, 33 patients who underwent living donor liver transplantation were included in this study. Cardiac output (CO) was measured using a PiCCO device (Pulsion Medical Systems, Munich, Germany). The mean systemic filling pressure was calculated using the inspiratory hold maneuver at four time intervals - at baseline, 10 min after the norepinephrine infusion, 5 min after norepinephrine discontinuation, and after infusion of 500 cc of 5% albumin. Other hemodynamic parameters, including the mean arterial pressure (MAP), pulse pressure variation, stroke volume variation, global end-diastolic volume, and mitral inflow velocity (E wave), were also evaluated. RESULTS: The norepinephrine infusion increased MAP and systemic vascular resistance in all patients. Moreover, it increased CO, mean systemic filling pressure, and global end-diastolic volume in 20 patients (60%), whereas there were no changes in these variables in 13 patients (40%). In all patients, norepinephrine infusion discontinuation caused a significant decrease in MAP, CO, resistance to venous return, and mean systemic filling pressure. Infusion of 500 cc colloid increased CO; however, interestingly, it was associated with a significant decrease in systemic vascular resistance; hence, MAP and mean systemic filling pressure showed no changes. CONCLUSIONS: The norepinephrine infusion at 0.1 µg-1 kg-1 min-1 was associated with an increase in CO in patients with liver cirrhosis undergoing liver transplantation. Norepinephrine's effect on CO was primarily attributable to an increase in venous return due to an increase in mean systemic filling pressure.

Urinary N-terminal Pro-Brain Natriuretic Peptide in Newborn Infants with Cardiac and Pulmonary Diseases.

OBJECTIVES: The aim of this study was to assess the feasibility of urinary N-terminal pro-brain natriuretic peptide (NT-proBNP) as noninvasive screening tool for congenital heart diseases in full-term neonates with respiratory distress. STUDY DESIGN: A prospective cohort study was conducted on 90 full-term infants. Newborn were assigned into three groups: pulmonary, cardiac, and control groups. Urinary NT-proBNP were measured in all studied groups at day 1 (NT-proBNP1) and day 5 (NT-proBNP5). RESULTS: Urinary NT-proBNP1 was higher in cardiac group compared with pulmonary and control groups (488 ± 91, 321 ± 80, and 218 ± 41 ng/L, respectively; p ≤ 0.001). NT-proBNP5 was lower in pulmonary and control group than cardiac group (245 ± 84, 137 ± 39, and 546 ± 284 ng/L, respectively, with p ≤ 0.001). Receiver operating characteristic (ROC) analysis was performed to assess predictive value of NT-proBNP1 in cardiac and pulmonary populations. ROC showed area under curve of 0.97 and cutoff point of ≥386.5 ng/L referring to a cardiac etiology with sensitivity of 93.3%, specificity of 86.7%, negative predictive value of 93%, and positive predictive value of 88%. CONCLUSION: Urinary NT-proBNP is feasible to be a noninvasive screening tool to predict congenital heart diseases in full-term neonates. Further studies are needed to assess the correlation between plasma and urinary levels of NT-proBNP in congenital heart diseases in full-term and preterm infants.

The validity of central venous to arterial carbon dioxide difference to predict adequate fluid management during living donor liver transplantation. A prospective observational study.

BACKGROUND: To assess the validity of central and pulmonary veno-arterial CO2 gradients to predict fluid responsiveness and to guide fluid management during liver transplantation. METHODS: In adult recipients (ASA III to IV) scheduled for liver transplantation, intraoperative fluid management was guided by pulse pressure variations (PPV). PPV of ≥15% (Fluid Responding Status-FRS) indicated fluid resuscitation with 250 ml albumin 5% boluses repeated as required to restore PPV to < 15% (Fluid non-Responding Status-FnRS). Simultaneous blood samples from central venous and pulmonary artery catheters (PAC) were sent to calculate central venous to arterial CO2 gap [C(v-a) CO2 gap] and pulmonary venous to arterial CO2 gap [Pulm(p-a) CO2 gap]. CO and lactate were also measured. RESULTS: Sixty seven data points were recorded (20 FRS and 47 FnRS). The discriminative ability of central and pulmonary CO2 gaps between the two states (FRS and FnRS) was poor with AUC of ROC of 0.698 and 0.570 respectively. Central CO2 gap was significantly higher in FRS than FnRS (P = 0.016), with no difference in the pulmonary CO2 gap between both states. The central and Pulmonary CO2 gaps are weakly correlated to PPV [r = 0.291, (P = 0.017) and r = 0.367, (P = 0.002) respectively]. There was no correlation between both CO2 gaps and both CO and lactate. CONCLUSION: Central and the Pulmonary CO2 gaps cannot be used as valid tools to predict fluid responsiveness or to guide fluid management during liver transplantation. CO2 gaps also do not correlate well with the changes in PPV or CO. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03123172 . Registered on 31-march-2017.

Validity of mini-fluid challenge for predicting fluid responsiveness following liver transplantation.

BACKGROUND: Mini-fluid challenge is a well tested and effective tool to predict fluid responsiveness under various clinical conditions. However, mini-fluid challenge has never been tested in patients with end-stage liver disease. This study investigated whether infusion of 150 ml albumin 5% can predict fluid responsiveness in cirrhotic patients following liver transplant. METHODS: Fifty patients receiving living donor liver transplant were included in the analysis. Mini-fluid challenge composed of 150 ml of albumin 5% administered over 1 min in three consecutive 50-ml fluid boluses. An additional 350 ml was then infused at a constant rate over 15 min (for a total of 500 ml). Stroke volume (SV) was measured as the product of the subaortic velocity time integral (VTI) and left ventricular outflow tract (LVOT) area. Fluid responsiveness was defined as an increase in SV by ≥15% after the infusion. RESULTS: Fifty patients were enrolled in the study. Fourteen patients were classified with Child A, 15 patients with Child B, and 21 patients with Child C cirrhosis. Thirty four patients were fluid responders and 16 patients were fluid non-responders. After 150 ml of albumin 5%, the SV increased significantly in our cohort. The area under receiver operating curve (AUROC) was 0.7 (95% confidence interval [CI] 0.5-0.8, P = 0.005). In subgroup analysis, the SV increased significantly after mini fluid challenge in the Child A group (P = 0.017) but not Child B or C groups (P = 0.3 and 0.29, respectively). The AUROC for mini-fluid challenge in the Child A group was 0.86 (95% confidence interval [CI] 0.6-0.9, P = 0.0004), while mini-fluid challenge failed to discriminate between responders and non-responders in Child B and C groups. CONCLUSION: A mini-fluid challenge of 150 ml albumin 5% can predict fluid responsiveness in liver transplant patients with fair sensitivity and specifiicty. Subgroup analyis revealed that minifluid challenge can predict fluid responsiveness in patients with Child A cirrhosis but not patients with Child B or C cirrhosis. TRIAL REGISTRATION: NCT03396159 . (Prospective registered). Initial registration date was 10/01/2018.

Breast discharge: ultrasound and Doppler evaluation.

BACKGROUND: Nipple discharge causes discomfort and anxiety to many women. Nipple discharge is most commonly associated with endocrine alterations and/or medications. These often result in duct ectasia and/or fibrocystic changes that may lead to discharge from one or several ducts. The most common cause of clinically significant discharge is intraductal growth of the ductal epithelium, due to hyperplasia, micropapillary proliferation, solitary papillomas and/or ductal carcinoma (both in situ and invasive). The aim of the study was to evaluate the role of the gray-scale ultrasound and colour Doppler in the diagnosis of intraductal pathology in patients with nipple discharge. PATIENTS AND METHODS: One hundred & seven patients were included in the study, (age range 23-65years). Standard mammographic views were taken. Ultrasound evaluation was performed for all cases; ductography for 20 cases and ductoscopy for 3 cases. US guided fine needle biopsy was done in 7 cases; microducectomy of affected duct was done in 20 cases and major duct excision in 5cases. Fibro-optic Ductoscopy is performed for 3 cases. RESULTS: Revision of biopsy specimens of 17 cases with intraluminal masses detected by US revealed: Six cases with intraductal carcinoma, intraductal papilloma in 7 cases, 1 case of ductal papillomatosis. Three cases showed atypical cells: Intraductal papilloma with atypia in 2 cases, proliferative hyperplasia with atypia in one case. Eighty eight cases had simple duct ectasia (51 bilateral multiple and 37 focal duct ectasia). No dilated ducts were detected in 2 cases. Fibro-optic Ductoscopy confirmed the presence of intraductal papilloma in one case, carcinoma in one case, no intraductal masses in the third case. A 6 months follow-up was requested for all cases with no detected intra luminal pathology. Ultrasound examination is highly sensitive (100%) but less specific (82.4%) in diagnosis of intraductal pathology. Colour & power Doppler are sensitive (94%) in detecting flow in intraductal echogenic masses to differentiate them from insipissated secretions. Colour and power Doppler raises specificity and diagnostic accuracy to 100%. Ductography is an underused procedure that is sensitive (100%) but less specific (60%) in characterization of intraductal filling defects. CONCLUSION: Ultrasonography is a mandatory complement to mammography in these cases, US guided fine needle biopsy is minimally invasive technique in confirming the diagnosis of suspicious mass. Ultrasound may also be a guide to fibro-optic ductoscope. KEY WORDS: Ductography - Nipple discharge - Intraductal carcinoma - Intraductal papilloma - In situ ductal carcinoma - Invasive ductal carcinoma - Duct ectasia - Breast ductoscopy.