Background
There is paucity of data on intermediate-term post liver transplant outcomes from South Asia. The objective of this study was to determine survival outcomes in patients who underwent ...living donor liver transplantation (LDLT) in a busy liver transplant center in Pakistan.
Methods
This study was a review of patients who underwent LDLT between 2012 and 2016. A total of 321 patients were included in this study. Early (within 90 days) and late (>90 days) morbidity and mortality was assessed. Estimated 1- and 4-year survival was determined.
Results
Median age was 48 (18–73) years. Male to female ratio was 4.5:1. Out of total 346 complications, 184 (57.3%) patients developed 276 (79.7%) complications in early post-transplant period, whereas there were 70 (21.3%) late complications. Most common early complication was pleural effusion in 46 (16.6%) patients. Biliary complications were the most common late complication and were seen in 31/70 (44.2%) patients. Overall 21.4% patients had a biliary complication. The 3-month mortality was 14%. The estimated 1- and 4-year OS for a MELD cutoff of 30 was 84.5 versus 72 and 80 versus 57% (
P
= 0.01). There was no donor mortality.
Conclusion
Acceptable intermediate-term post-transplant outcomes were achieved with LDLT. There is a need to improve outcomes in high-MELD patients.
Both gene expression profiling in postmortem human brain and studies using animal models have implicated the fibroblast growth factor (FGF) family in affect regulation and suggest a potential role in ...the pathophysiology of major depressive disorder (MDD). FGF2, the most widely characterized family member, is down-regulated in the depressed brain and plays a protective role in rodent models of affective disorders. By contrast, using three microarray analyses followed by quantitative RT-PCR confirmation, we show that FGF9 expression is up-regulated in the hippocampus of individuals with MDD, and that FGF9 expression is inversely related to the expression of FGF2. Because little is known about FGF9’s function in emotion regulation, we used animal models to shed light on its potential role in affective function. We found that chronic social defeat stress, an animal model recapitulating some aspects of MDD, leads to a significant increase in hippocampal FGF9 expression, paralleling the elevations seen in postmortem human brain tissue. Chronic intracerebroventricular administration of FGF9 increased both anxiety- and depression-like behaviors. In contrast, knocking down FGF9 expression in the dentate gyrus of the hippocampus using a lentiviral vector produced a decrease in FGF9 expression and ameliorated anxiety-like behavior. Collectively, these results suggest that high levels of hippocampal FGF9 play an important role in the development or expression of mood and anxiety disorders. We propose that the relative levels of FGF9 in relation to other members of the FGF family may prove key to understanding vulnerability or resilience in affective disorders.
Biliary complications are the most common post-liver transplant (LT) complications with an incidence of 15%-45%. Furthermore, such complications are reported more frequently in patients who undergo a ...living-donor LT compared to a deceased-donor LT. Most post-LT biliary complications involve biliary strictures, bile leakage, and biliary stones, although many rarer events, such as hemobilia and foreign bodies, contribute to a long list of related conditions. Endoscopic treatment of post-LT biliary complications has evolved rapidly, with new and effective tools improving both outcomes and success rates; in fact, the latter now consistently reach up to 80%. In this regard, conventional endoscopic retrograde cholangiopancreatography remains the preferred initial treatment. However, percutaneous transhepatic cholangioscopy is now central to the management of endoscopy-resistant cases involving complex hilar or multiple strictures with associated stones. Many additional endoscopic tools and techniques-such as the rendezvous method, magnetic compression anastomosis , and peroral cholangioscopy-combined with modified biliary stents have significantly improved the success rate of endoscopic management. Here, we review the current status of endoscopic treatment of post-LT biliary complications and discuss conventional as well as the aforementioned new tools and techniques.
Living donor liver transplantation (LDLT) is an established treatment for patients with cirrhosis and hepatocellular carcinoma (HCC) within Milan criteria. Acceptable outcomes have been demonstrated ...in patients fulfilling extended criteria. Here, we share our experience with LDLT for patients with HCC within and beyond Milan criteria, with emphasis on poor prognostic factors.
We retrospectively reviewed patients who underwent LDLT between 2012 and 2017 and had HCC proven on explant liver histopathology. A total of 117 patients were included. Patients who died early after transplant (in <30 days) were excluded. For outcomes, patients were divided into prognostic groups. These groups were based on (1) alpha fetoprotein >600, (2) poor differentiation, and (3) the presence of lymphovascular invasion. Recurrence-free survival (RFS) was determined using Kaplan–Meier curves.
Median age was 53 (30–73) years. Median follow-up was 20.3 (1–63.2) months. Median model for end stage liver disease (MELD) score was 19 (9–34). Of a total of 117 patients, 74 (63.2%) patients met Milan criteria. Recurrence rate was 12/117 (10.3%). Actuarial 5-year RFS was 88% and 82% (P = 0.3) in patients within and outside Milan criteria. There was no difference in 3-year RFS in patients with 0, 1, or 2 poor prognostic factors within Milan criteria (92%, 87%, and 75%, respectively; P = 0.3). However, a significant difference in RFS was seen in patients outside Milan criteria (92%, 93%, and 53%; P = 0.03).
Patients within Milan criteria have acceptable RFS even in the presence of poor prognostic factors. However, the presence of two or more poor prognostic variables significantly impacts RFS of patients outside Milan criteria.
The European association for the study of the liver and chronic liver failure consortium (EASL-CLIF) recently proposed diagnostic criteria for acute on chronic liver failure (ACLF). There is lack of ...data regarding liver transplant outcomes in ACLF patients based on these criteria. The objective of this study was to determine outcome following living donor liver transplantation (LDLT) in ACLF patients.
We retrospectively reviewed patients who underwent LDLT for ACLF based on European association for the study of the liver and chronic liver failure consortium (EASL-CLIF) diagnostic criteria (group 1) (N=60) and compared them with ACLF patients who did not undergo transplantation (group 2) (N=59). The primary outcome of interest was 30 day mortality. We also looked at one year survival in these patients. Survival was calculated using Kaplan–Meier curves and Log rank test was used to determine significance between variables.
Median MELD scores for group 1 and 2 patients in ACLF grade 1 was 28 (20–38) and 31 (24–36), in ACLF grade 2 was 35 (24–42) and 36 (24–42) and in ACLF grade 3 was 36 (29–42) and 38 (32–52). For group 1 and 2, 30 day mortality in ACLF grade 1, 2 and 3 was 2/43(4.6%) versus 9/15(60%) (P<0.001), 1/15 (6.6%) versus 13/19 (68.4%), 0/2 (0%) versus 20/25 (80%) (P<0.001). Actuarial 1 year overall survival was 92% versus 11% (P<0.001) in patients who underwent transplantation versus those who did not. One year survival in patients with grade 1 and 2 ACLF who received transplant versus medical treatment was 91% versus 13% and 93% versus 15% (P<0.001) respectively.
LDLT has excellent outcomes in patients with EASL-CLIF grade 1 and 2 ACLF. Without transplantation, ACLF patients have a very poor prognosis.
Hepatocellular carcinoma (HCC) ranks second amongst all causes of cancer deaths globally. It is on a rise in Pakistan and might represent the most common cancer in adult males. Pakistan contributes ...significantly to global burden of hepatitis C, which is a known risk factor for HCC, and has one of the highest prevalence rates (>3%) in the world. In the absence of a national cancer registry and screening programs, prevalence of hepatitis and HCC only represents estimates of the real magnitude of this problem. In this review, we present various aspects of HCC in Pakistan, comparing and contrasting it with the global trends in cancer care. There is a general lack of awareness regarding risk factors of HCC in Pakistani population and prevalence of hepatitis C has increased. In addition, less common risk factors are also on a rise. Majority of patients present with advanced HCC and are not eligible for definitive treatment. We have attempted to highlight issues that have a significant bearing on HCC outcome in Pakistan. A set of strategies have been put forth that can potentially help reduce incidence and improve HCC outcome on national level.
•Urocortin-1 neurons were mapped within the Edinger–Westphal nucleus.•Urocortin-1-containing neurons within the Edinger–Westphal nucleus are distributed in a distinct rostral–caudal pattern.•Some of ...these urocortin-1 neurons also express cholinergic markers.•Neurons within the Edinger–Westphal nucleus send poly-synaptic projections to skeletal muscle and the adrenal gland.•Some of the Edinger–Westphal neurons that poly-synaptically project to the periphery express urocortin-1.
Numerous motivated behaviors require simultaneous activation of somatomotor and autonomic functions. We have previously characterized the organization of brain circuits that may mediate this integration. Presympathetic premotor neurons (PSPMNs) that are part of such circuits are distributed across multiple brain regions, which mediate stress-elicited behavioral and physiological responses, including the Edinger–Westphal nucleus (EW). Based on its connectivity and function, EW has recently been re-classified into a preganglionic (EWpg) and a centrally projecting (EWcp) population. Neurons within EWcp are the major source of urocortin 1 (Ucn-1), an analog of the corticotropin-releasing factor that binds the CRFR1 and CRFR2 receptors and has been implicated in mediating homeostatic responses to stress. We hypothesized that a subset of EWcp PSPMNs expresses Ucn-1. Utilizing dual-label immunofluorescence, we initially mapped the distribution of Ucn-1 and cholinergic neurons within EW in colchicine pre-treated rats. Based on this labeling we divided EWcp into three neuroanatomical levels. To examine connections of EWcp neurons to the gastrocnemius muscle and the adrenal gland, we next employed trans-synaptic tract-tracing in a second group of rats, utilizing two pseudorabies virus (PRV) recombinants that express unique reporter proteins. Using multi-label immunofluorescent staining, we identified the presence of Ucn-1-positive PSPMNs, dually labeled with PRV and present throughout the entire extent of EWcp and intermingled with Ucn-1 neurons infected with one or neither of the viral recombinants. Compared to rats pretreated with colchicine, we observed significantly fewer Ucn-1 neurons in animals that received PRV injections. Post hoc analyses revealed significantly fewer Ucn-1 neurons at the rostral level as compared to the caudal and middle levels. These data suggest functional and anatomic heterogeneity within EWcp; this organization may coordinate various aspects of stress-elicited and emotionally salient behaviors.
Background
Living donor liver transplantation (LDLT) involves healthy individuals undergoing voluntary major hepatic resection. LDLT program only started in 2012 in Pakistan and its impact on donor’s ...quality of life (QOL) post resection is not known. The objective of this study was to determine health-related QOL in donors who underwent hepatectomy in country’s first liver transplant program.
Methods
A total of 60 donors who underwent hepatectomy between 2012 and 2014 with a minimum follow-up of 6 months were included in the study. Short form (SF-36) and Profile of mood states (POMS-65) was used to assess QOL. In addition scores were compared between patients who did and did not develop complications.
Result
Mean time duration between hepatectomy and administration of questionnaire was 15 ± 5.1 months. Median age was 28 (19–45) years. Mean BMI was 24.4 ± 3.7. A total of 7 (11.6 %) Grade 3 and above complications were observed in donors. Donors exceeded a score of 90 in 6 out of 8 evaluated categories on SF-36. The highest mean score was recorded for emotional role limitation 95.5 ± 17.1 and lowest for energy 84.8 ± 17.5. The mean score for anger was 6.6 ± 7.5. Donors also did well on the POMS vigor score with a mean of 22.7 ± 5. No significant difference in scores was observed between donors with and without complications for any of the categories except tension. Donors who developed complications post-operatively had a significantly low mean tension score of 1.5 versus 3.8 for donors without complications.
Conclusion
Acceptable post donation QOL was achieved and surgical complications did not adversely affect SF-36 and POMS scores.
Introduction The impact of donor age on liver transplantation is well known. Data on an appropriate donor age cut-off for living donor liver transplantation (LDLT) with a background of hepatitis C ...(HCV) is generally limited. The objective of this study was to determine whether limiting donor age to less than 35 years improved outcomes in patients with HCV-related end-stage liver disease (ESLD). Methods This was a retrospective review of 169 patients who underwent LDLT for HCV-related ESLD. The patients were divided into two groups based on whether they received grafts from donors ≤ 35 (Group 1) or > 35 (Group 2) years of age. Kaplan Meier curves were used to determine survival. Uni and multivariate analysis were performed to determine independent predictors of mortality. Results Mean donor age was 25.1 ± 5.2 and 40.1 ± 3.4 years (P < 0.0001). Early allograft dysfunction (EAD) was seen in 11.7% patients in Group 1 versus 29.6% in Group 2 (P = 0.02). A significant difference in mortality was present between the two groups, i.e., 33.3% versus 15.8% (P = 0.04). The estimated four-year overall survival (OS) was 78% and 64% (P = 0.03). Upon doing univariate analysis, the donor age (P = 0.04) and EAD (P = 0.006) were found to be significant variables for mortality. On multivariate analysis, EAD was the only independent predictor of mortality (Hazard ratio: 2.6; confidence interval: 1.1 - 5.8; P = 0.01). Conclusion Opting for younger donors (≤ 35 years) for HCV-related ESLD patients lowers the risk of EAD and improves overall survival.
Background. Concomitant vascular injury might adversely impact outcomes after iatrogenic bile duct injury (IBDI). Whether a new HPB center should embark upon repair of complex biliary injuries with ...associated vascular injuries during learning curve is unknown. The objective of this study was to determine outcome of surgical management of IBDI with and without vascular injuries in a new HPB center during its learning curve. Methods. We retrospectively reviewed patients who underwent surgical management of IBDI at our center. A total of 39 patients were included. Patients without (Group 1) and with vascular injuries (Group 2) were compared. Outcome was defined as 90-day morbidity and mortality. Results. Median age was 39 (20–80) years. There were 10 (25.6%) vascular injuries. E2 injuries were associated significantly with high frequency of vascular injuries (66% versus 15.1%) (P=0.01). Right hepatectomy was performed in three patients. Out of these, two had a right hepatic duct stricture and one patient had combined right arterial and portal venous injury. The number of patients who developed postoperative complications was not significantly different between the two groups (11.1% versus 23.4%) (P=0.6). Conclusion. Learning curve is not a negative prognostic variable in the surgical management of iatrogenic vasculobiliary injuries after cholecystectomy.
PDF
