Endothelial Cell APOE3 Regulates Neurovascular, Neuronal, and Behavioral Function.

BACKGROUND: Specialized brain endothelial cells and human APOE3 are independently important for neurovascular function, yet whether APOE3 expression by endothelial cells contributes to brain function is currently unknown. In the present study, we determined whether the loss of endothelial cell APOE3 impacts brain vascular and neural function. METHODS: We developed APOE3fl/fl/Cdh5(PAC)-CreERT2+/- (APOE3Cre+/-) and APOE3fl/fl/Cdh5(PAC)-CreERT2-/- (APOE3Cre-/-, control) mice and induced endothelial cell APOE3 knockdown with tamoxifen at ≈4 to 5 weeks of age. Neurovascular and neuronal function were evaluated by biochemistry, immunohistochemistry, behavioral testing, and electrophysiology at 9 months of age. RESULTS: We found that the loss of endothelial APOE3 expression was sufficient to cause neurovascular dysfunction including higher permeability and lower vessel coverage in tandem with deficits in spatial memory and fear memory extinction and a disruption of cortical excitatory/inhibitory balance. CONCLUSIONS: Our data collectively support the novel concept that endothelial APOE3 plays a critical role in the regulation of the neurovasculature, neural circuit function, and behavior.

Nonalcoholic Fatty Liver Disease in Living Donor Liver Transplant Recipients: A Histology-Based Study.

Background: Recurrent or de novo nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are common after liver transplantation (LT) and may be associated with rapid progression to fibrosis; however, there is limited data in this regard after living donor liver transplantation (LDLT). Material and methods: This is a retrospective study at a high volume LDLT center of all liver biopsies performed in patients with post-transplant NAFLD diagnosed on ultrasound of the abdomen. Liver biopsy was indicated for raised transaminases and/or high liver stiffness on TE. The association between these prebiopsy parameters and inflammation and fibrosis on histology was analyzed. Data are shown as mean ± standard deviation or median (25-75 interquartile range). Results: The study cohort consisted of 31 males and 3 females, aged 43 ± 10 years. The LT to liver biopsy interval was 44 (28-68) months. The prebiopsy AST and ALT were 71 (38-119) and 66 (50-156), respectively. The histology suggested no nonalcoholic steatohepatitis (NASH) in 7 (20%), borderline NASH in 15 (44%), and NASH in 12 (35%) patients. A total of 15 patients (44%) had stage 1 or stage 2 fibrosis. The proportion of patients having fibrosis was significantly higher in patients with NASH (83%) compared to patients with borderline NASH (33%) or no NASH (none had fibrosis, P = 0.001). Among 18 patients who underwent TE (on FibroScan), liver stiffness was significantly higher in patients with fibrosis [18.1 (9.7-22.5)] than in those without fibrosis [9.7 (4.0-12.7); P = 0.043]. Conclusion: Over a third of the LDLT recipients with post-transplant NAFLD developed NASH, and nearly half, borderline NASH 3-5 years after transplant. Most with established NASH also had fibrosis on histology. Prevention of risk factors and early diagnosis is warranted in these patients.

Restructuring Living-Donor Liver Transplantation at a High-Volume Center During the COVID-19 Pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has led to deferral of elective transplants and proactive pretransplant testing of the donor/recipient. The impact of these on living-donor liver transplantation (LDLT) activity and outcome is not known. We performed LDLT only for sick patients or patients with advanced hepatocellular carcinoma in this period, with special COVID protocols. METHODS: Patients undergoing LDLT counseling, evaluation, and transplant in the period March to June 2020 (group A) under COVID-19 restrictions and special protocols were included. LDLT activity and outcomes among these patients were compared with those in the same period in 2019 (group B). RESULTS: In the period March 15-June 10, we performed 39 and 23 (59%) LDLTs in 2019 and 2020, respectively. The adult patients with cirrhosis in group A (n = 20) had a significantly higher MELD score, 19.8 ± 7.0 versus 16.1 ± 5.6 in group B (n = 36), p = 0.034. Early recipient mortality was similar in 2019 (2/39) and 2020 (2/23). One of 23 post-transplant recipients, 3/71 recipients and donors during evaluation, and 8/125 healthcare workers (HCWs) developed COVID-19, all of whom recovered uneventfully. CONCLUSION: LDLT activity substantially reduced during the COVID era. The incidence and outcome of COVID-19 among the waiting or transplanted patients and HCWs were similar to those of the general population. The outcome after LDLT in the COVID era was similar to that in non-COVID times. These data suggest that LDLT may be extended to more stable patients with strict protocols.

Incorporating Tumor Biology to Predict Hepatocellular Carcinoma Recurrence in Patients Undergoing Living Donor Liver Transplantation Using Expanded Selection Criteria.

Conventional selection criteria for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) are based on tumour size/number only, and do not consider vital surrogates of tumor biology such as alpha-fetoprotein (AFP) and tumor [18 F]fluorodeoxyglucose positron emission tomography ([18 F]FDG PET) avidity. We analyzed survival outcomes, and predictors of HCC recurrence in 405 patients with cirrhosis and HCC (HCC-cirr) who underwent living donor LT (LDLT) using our expanded selection criteria: no extrahepatic disease or major vascular invasion, irrespective of tumor size/number. Fifty-one percent patients had tumours beyond Milan, and 43% beyond the University of California San Francisco [UCSF] criteria. The 5-year overall survival (OS) and recurrence-free survival (RFS) were 64% and 70%, respectively. Three preoperatively available factors predicted recurrence: pre-LT AFP ≥100 ng/mL (P = 0.005; hazard ratio [HR], 2.190), tumor burden beyond the UCSF criteria (P = 0.001; HR, 2.640), and [18 F]FDG PET avidity (P = 0.004; HR, 2.442). A prognostic model based on the number and combination of the aforementioned preoperative risk factors was developed using a competing-risk RFS model. Three risk groups were identified: low (none or a single risk factor present, 9.3% recurrence), moderate (AFP ≥100 ng/mL and [18 F]FDG PET avidity, or beyond UCSF tumor and [18 F]FDG PET avidity, 25% recurrence), and high (AFP ≥100 ng/mL and beyond UCSF, or presence of all 3 risk factors, 46% recurrence). Acceptable long-term outcomes were achieved using our expanded selection criteria. Our prognostic model to predict recurrence based on preoperative biological and morphological factors could guide pretransplant management (downstaging versus upfront LDLT) with the aim of reducing post-LDLT recurrence.

Delayed Graft Dysfunction due to Invasive Hepatic Mucormycosis After Living Donor Liver Transplantation.

Mucormycosis is a rare but emerging fungal infection complicating solid organ transplantation. It is associated with a high mortality rate. We describe an unusual case of hepatic mucormycosis in a living donor liver transplant recipient presenting as delayed graft dysfunction, which was successfully treated with combination of liposomal amphotericin B and oral posaconazole therapy, without surgical resection. The patient had clinical improvement with normalization of liver function tests.

Survey of preoperative management protocol for perihilar cholangiocarcinoma at 10 Japanese high-volume centers with a combined experience of 2,778 cases.

BACKGROUND: In Japan, strategies for preoperative management of perihilar cholangiocarcinoma (PHC) have evolved over the last decade; the operative mortality has significantly reduced to <5%. METHODS: A questionnaire was sent to 10 institutions based on their case volume. Questionnaire was based on: (1) preoperative biliary drainage, (2) bile replacement, (3) role of synbiotics, (4) remnant liver volume enhancement, (5) predicted remnant liver function, (6) imaging, (7) nutrition, and (8) role of Inchinkoto. RESULTS: The median case volume was 226 (range 105-889) cases, respectively. Eight institutions preferred endoscopic nasobiliary drainage and two preferred endoscopic biliary stenting for biliary drainage. Nine used bile replacement within 2-3 days of biliary drainage. Four used synbiotics preoperatively. The median cutoff value for future remnant liver volume and serum total bilirubin, at which portal vein embolization (PVE) is done, is <40% and <4 mg/dl. The median interval between PVE and surgery was 3-4 weeks. To predict remnant liver function, indocyanine green retention (n = 8) and clearance rate (n = 2) were mainly used. Five used Inchinkoto to improve liver function. Nine used multidetector computed tomography and direct cholangiography for surgical planning. CONCLUSION: With appropriate preoperative management of PHC, surgical morbidity and mortality can be reduced. This survey can provide recommendations to improve PHC perioperative outcomes.

Comparative Microbiological Evaluation after Caries Removal by Various Burs.

AIM: The aim of the study was to compare the caries removal efficacy in terms of bacteriology and efficiency in terms of time taken by conventional and smart burs. MATERIALS AND METHODS: A total of 40 extracted permanent molars with occlusal caries were selected for this study. These teeth were split at the center of carious lesion buccolingually, in order to obtain two similar halves. Thus, 80 samples were obtained in this way and were randomly divided into 2 groups of 40 samples each. Caries was removed using conventional burs in group I and polymer bur Smartprep (SS white) in group II. The time involved in caries removal was measured for both the groups. After excavation of all carious lesions, the samples were decalcified, dehydrated, and embedded in paraffin wax from which thin sections of 5 µm were obtained, which were histologically evaluated for bacterial presence under a light microscope. RESULTS: An intergroup comparison between conventional bur (group I) and smart bur (group II) showed a statistically nonsignificant difference in terms of the presence of microorganisms after caries removal with a p value of 0.073638 (p > 0.05). However, the time taken for caries removal was significantly more for smart burs than diamond burs with a p value of 0.001 (p < 0.05). CONCLUSION: The polymer burs were found to be as effective as the conventional burs in terms of microbial presence after caries removal, but are more time-consuming than conventional burs. HOW TO CITE THIS ARTICLE: Somani R, Chaudhary R, Jaidka S, et al. Comparative Microbiological Evaluation after Caries Removal by Various Burs. Int J Clin Pediatr Dent 2019;12(6):524-527.

A Worldwide Survey of Live Liver Donor Selection Policies at 24 Centers With a Combined Experience of 19 009 Adult Living Donor Liver Transplants.

BACKGROUND: Although surgical technique in living donor liver transplantation (LDLT) has evolved with a focus on donor safety and recipient challenges, the donor selection criteria remain considerably disparate. METHODS: A questionnaire on donor selection was sent to 41 centers worldwide. 24 centers with a combined experience of 19 009 LDLTs responded. RESULTS: Centers were categorized into predominantly LDLT (18) or deceased donor liver transplantation (6), and high- (10) or low-volume (14) centers. At most centers, the minimum acceptable graft-to-recipient weight ratio was 0.7 or less (67%), and remnant was 30% (75%). The median upper limit of donor age was 60 years and body mass index of 33 kg/m. At 63% centers, age influenced the upper limit of body mass index inversely. Majority preferred aspartate transaminase and alanine transaminase less than 50 IU/mL. Most accepted donors with nondebilitating mild mental or physical disability and rejected donors with treated coronary artery disease, cerebrovascular accident and nonbrain, nonskin primary malignancies. Opinions were divided about previous psychiatric illness, substance abuse and abdominal surgery. Most performed selective liver biopsy, commonly for steatosis, raised transaminases and 1 or more features of metabolic syndrome. On biopsy, all considered macrovesicular and 50% considered microvesicular steatosis important. Nearly all (92%) rejected donors for early fibrosis, and minority for nonspecific granuloma or mild inflammation. Most anatomical anomalies except portal vein type D/E were acceptable at high-volume centers. There was no standard policy for preoperative or peroperative cholangiogram. CONCLUSIONS: This first large live liver donor survey provides insight into donor selection practices that may aid standardization between centers, with potential expansion of the donor pool without compromising safety.

ENBD is Associated with Decreased Tumor Dissemination Compared to PTBD in Perihilar Cholangiocarcinoma.

BACKGROUND: Little is known regarding the risk of tumor dissemination when percutaneous biliary drainage is used before surgical resection of perihilar cholangiocarcinoma (PHC). We aimed to compare the incidence of tumor dissemination after preoperative endoscopic nasobiliary drainage (ENBD) with that after percutaneous transhepatic biliary drainage (PTBD) for PHC. METHODS: Data from 208 consecutive patients who underwent PHC resection between 2000 and 2013 were retrospectively analyzed. The influence of drainage type on incidence of tumor dissemination was examined. Seventy-six patients underwent ENBD (37%), 87 underwent PTBD (42%), and 45 underwent surgery without preoperative biliary drainage (WD, 22%). RESULTS: The respective 2- and 5-year estimated cumulative incidences of tumor dissemination in the ENBD group (11.8/14.6%) were lower than in the PTBD group (28.8/35.9%, p = 0.003) and equivalent to that in the WD group (11.2/15.9%, p = NS). PTBD (hazard ratio [HR] vs. ENBD, 2.80) was an independent risk factor for postoperative tumor dissemination in the multivariate analysis. The 2- and 5-year disease-specific survival rates were higher in the ENBD group (67.6/47.3%) than in the PTBD group (56.6/27.8%, p = 0.032) and equivalent to that in the WD group (64.9/53.8%, p = NS). However, drainage type was not an independent risk factor in multivariate analysis of disease-specific survival. CONCLUSION: For patients with PHC, the associated risk of postoperative tumor dissemination in the ENBD group was lower than in the PTBD group and equivalent to that in the WD group. Thus, ENBD is the ideal procedure for preoperative biliary drainage.

Robotic-assisted right hepatectomy via anterior approach for intrahepatic cholangiocarcinoma.

Major hepatic resection, especially right hepatectomy, has been successfully performed by specialized hepatobiliary centers using the robotic platform with low morbidity, conversion rates and outcomes comparable to laparoscopic and open surgery. The authors report a case of robotic-assisted right hepatectomy done for intrahepatic cholangiocarcinoma using anterior approach, after right portal vein embolisation for future liver remnant volume enhancement.

Parosteal lipoma of humerus-A rare case.

INTRODUCTION: Parosteal lipoma is an extremely rare benign tumor composed mainly of mature adipose tissue with a bony component. PRESENTATION OF CASE: This study reports the case of a 65-year old woman with a big mass on the posteromedial aspect of the right upper arm since 1 year. The swelling was a slow growing, painless, nontender, immobile mass which was not fixed to skin. She had no complaints of painful or restricted movements of the shoulder joint. She had no history of trauma to the upper limb. MRI revealed a large 13cm×5cm×8cm well defined, nonenhancing, lobulated, heterointense, predominantly fat intensity lesion with a small area of chondroid component measuring 2cm×1.6cm in posteromedial aspect of proximal right humerus, seen completely separate from the adjacent muscles. DISCUSSION: The patient underwent surgery under general anesthesia. Vertical elliptical incision was taken over the posterior border of the upper arm over the mass. The tumor was below the lower part of deltoid near the upper end of humerus, which formed the roof, and between the long and medial heads of triceps muscles. A part of tumor, measuring 6cm×5cm×5cm, was under the long head of triceps displacing it along with radial nerve and vessels medially while the other part, measuring 7cm×6cm×3cm, was under the medial head of triceps displacing it laterally. The tumor was excised undocking its periosteal attachment. The specimen weighed 250g. On histopathology, the lesion was composed of mature lipocytes that had an intimate relationship with the periosteum. No cellular atypia or lipoblasts were seen. CONCLUSION: Parosteal lipomas are rare neoplasias with no proven malignant potential. These tumors can be resected without much damage to the adjacent structures, thus preserving the function of the upper limb.