Spatial and spectral measurement of laser-driven protons through radioactivation

The simultaneous measurement of the spatial profile and spectrum of laser-accelerated protons is important for further optimization of the beam qualities and applications.We report a detailed study regarding the underlying physics and regular procedure of such a measurement through the radioactivation of a stack composed of aluminum,copper,and CR-39 plates as well as radiochromic films(RCFs).After being radioactivated,the copper plates are placed on imaging plates(IPs)to detect the positrons emitted by the reaction products through contact imaging.The spectrum and energy-dependent spatial profile of the protons are then obtained from the IPs and confirmed by the measured ones from the RCFs and CR-39 plates.We also discuss the detection range,influence of electrons,radiation safety,and spatial resolution of this measurement.Finally,insights regarding the extension of the current method to online measurements and dynamic proton imaging are also provided.

Clinicopathological features and prognosis of combined hepatocellular carcinoma and cholangiocarcinoma after surgery

BACKGROUND： Combined hepatocellular carcinoma and cholangiocarcinoma （cHCC-CC） is a rare subtype of primary liver cancer consisting of both hepatocellular carcinoma （HCC） and cholangiocarcinoma （CC）. Because of the rarity of this tumor, its feature is poorly understood. The present study aimed to evaluate the clinicopathological features and long-term prognosis of patients with cHCC-CC after surgery and to compare with those of the patients with stage-matched HCC and CC. METHODS： The dinicopathological features of the patients who underwent surgery for cHCC-CC at our center during the period of 2001-2010 were retrospectively analyzed and compared with those of stage-matched HCC and CC patients. Cancer staging was performed according to the AJCC Cancer Staging Manual （6th ed.）. Overall survival and disease-free survival were compared among the groups and prognostic factors of cHCC-CC were evaluated. RESULTS： Significant differences were observed in clinico- pathological features among 42 patients with cHCC-CC, 90 patients with HCC and 45 patients with CC. Similar to HCC patients, cHCC-CC patients had frequent hepatitis B virus antigen positivity, microscopic vessel invasion, cirrhosis and high level of serum alpha-fetoprotein. Similar to CC patients, cHCC-CC patients showed increased bile duct invasion and decreased capsule. The 1-, 3-, and 5-year overall survival and disease- free survival of patients with cHCC-CC were not significantly different from those with stage-matched patients with CC;but significantly poorer than those with HCC. In subanalysis of patients with stage Ⅱ, the overall survival in patients with cHCC-CC or CC was significantly poorer than that in patients with HCC. We did not find the difference in patients with other stages. Univariate analysis of overall and disease-free survival of patients with cHCC-CC showed that the vascular invasion and intrahepatic metastasis were the significant predictive factors. CONCLUSION： Patients with cHCC-CC showed similar dinico- pathological features as those with HCC or CC, and patients with cHCC-CC or CC had a poorer prognosis compared with those with HCC, especially at matched stage Ⅱ.

High-dose hepatitis B immunoglobulin therapy in hepatocellular carcinoma with hepatitis B virus-DNA/hepatitis B e antigen-positive patients after living donor liver transplantation

AIM: To investigate the impact of high-dose hepatitis B immunoglobulin(HBIG) on hepatocellular carcinoma(HCC) and hepatitis B virus(HBV) recurrence and overall survival after living donor liver transplantation(LDLT).METHODS: We investigated 168 patients who underwent LDLT due to HCC, and who were HBV-DNA/hepatitis B e antigen(HBe Ag)-positive, from January 2008 to December 2013. After assessing whether the patients met the Milan criteria, they were assigned to the low-dose HBIG group and high-dose HBIG group. Using the propensity score 1:1 matching method, 38 and 18 pairs were defined as adhering to and not adhering to the Milan criteria. For each pair, HCC recurrence, HBV recurrence and overall survival were analyzed by the Kaplan-Meier method and the log rank test according to the HBIG dose. RESULTS: Among those who met the Milan criteria, the 6-mo, 1-year, and 3-year HCC recurrence-free survival rates were 88.9%, 83.2%, and 83.2% in the low-dose HBIG group and 97.2%, 97.2%, and 97.2% in the high-dose HBIG group, respectively(P = 0.042).In contrast, among those who did not meet the Milan criteria, HCC recurrence did not differ according to the HBIG dose(P = 0.937). Moreover, HBV recurrence and overall survival did not differ according to the HBIG dose among those who met(P = 0.317 and 0.190, respectively) and did not meet(P = 0.350 and 0.987, respectively) the Milan criteria. CONCLUSION: High-dose HBIG therapy can reduce HCC recurrence in HBV-DNA/HBe Ag-positive patients after LDLT.

Graft-to-recipient weight ratio lower to 0.7% is safe without portal pressure modulation in right-lobe living donor liver transplantation with favorable conditions

BACKGROUND: The low graft-to-recipient weight ratio(GRWR) in adult-to-adult living donor liver transplantation(LDLT) is one of the major risk factors affecting graft survival. The goal of this study was to evaluate whether the lower limit of the GRWR can be safely reduced without portal pressure modulation in right-lobe LDLT. METHODS: From 2005 to 2011, 317 consecutive patients from a single institute underwent LDLT with right-lobe grafts without portal pressure modulation. Of these, 23 had a GRWR of less than 0.7%(group A), 27 had a GRWR of ≥0.7%, 【0.8%(group B), and 267 had a GRWR of more than and equal to 0.8%(group C). Medical records, including recipient, donor, operation factors, laboratory findings and complications were reviewed retrospectively. RESULTS: The baseline demographics showed low model for end-stage liver disease score(mean 16.3±8.9) and high percentage of hepatocellular carcinoma(231 patients, 72.9%). Three groups by GRWR demonstrated similar characteristics except recipient body mass index and donor gender. For smallforsize syndrome, there were 3(13.0%) in group A, 1(3.7%) in group B, and 2 patients(0.7%) in group C(P【0.001). Hepatic artery thrombosis was more frequently observed in group A than in groups B and C(8.7% vs 3.7% vs 1.9%, P=0.047). However, among the three groups, graft survival rates at 1 year(100% vs 96.3% vs 93.6%) and 3 years(91.7% vs 73.2% vs 88.1%) were not different(P=0.539). In laboratory measurements,there was no group difference in total bilirubin and albumin. However, prothrombin time was longer in group A within postoperative 1 week and platelet count was lower in groups A and B within postoperative 1 month. CONCLUSION: A GRWR lower to 0.7% is safe and does not need to modulate portal pressure in adult-to-adult LDLT using the right-lobe in favorable conditions including low model for end-stage liver disease score.

Outcomes after liver transplantation in accordance with ABO compatibility: A systematic review and meta-analysis

AIM To evaluate the differences in outcomes between ABOincompatible(ABO-I) liver transplantation(LT) and ABO-compatible(ABO-C) LT.METHODS A systematic review and meta-analysis were performed by searching eligible articles published before November 28, 2016 on MEDLINE(Pub Med), EMBASE, and Cochrane databases. The primary endpoints were graft survival, patient survival, and ABO-I-related complications. RESULTS Twenty-one retrospective observational studies with a total of 8247 patients were included in this metaanalysis. Pooled results of patient survival for ABO-I LT were comparable to those for ABO-C LT. However, ABO-I LT showed a poorer graft survival than ABO-C LT(1-year: OR = 0.66, 95%CI: 0.57-0.76, P < 0.001; 3-year: OR = 0.74, 95% CI 0.64-0.85, P < 0.001; 5-yearr: OR =0.75, 95%CI: 0.66-0.86, P < 0.001). Furthermore, ABO-I LT was associated with more incidences of antibody-mediated rejection(OR = 74.21, 95%CI: 16.32-337.45, P < 0.001), chronic rejection(OR =2.28, 95%CI: 1.00-5.22, P = 0.05), cytomegalovirus infection(OR = 2.64, 95%CI: 1.63-4.29, P < 0.001), overall biliary complication(OR = 1.52, 95%CI: 1.01-2.28, P = 0.04), and hepatic artery complication(OR = 4.17, 95%CI: 2.26-7.67, P < 0.001) than ABO-C LT. In subgroup analyses, ABO-I LT and ABO-C LT showed a comparable graft survival in pediatric patients and those using rituximab, and ABO-I LT showed an increased acute cellular rejection in cases involving deceased donor grafts.CONCLUSION Although patient survival in ABO-I LT was comparable to that in ABO-C LT, ABO-I LT was inferior to ABO-C LT in graft survival and several complications. Graft survival of ABO-I LT could be comparable to that of ABO-C LT in pediatric patients and those using rituximab.

A comparison of desensitization methods: Rituximab with/without plasmapheresis in ABO-incompatible living donor liver transplantation

Background: Plasmapheresis is a desensitization method used prior to ABO-incompatible(ABO-I) living donor liver transplantation. However, studies on its usefulness in the rituximab era are lacking.Methods: Fifty-six adult patients underwent ABO-I living donor liver transplantation between January2012 and October 2015. A single dose of rituximab(300 mg/m~2) was administered 2 weeks before surgery with plasmapheresis in all patients until February 2014(RP group, n = 26). Patients were administered rituximab only, without plasmapheresis between March 2014 and October 2015(RO group, n = 30).Results: The 6-, 12-and 18-month overall survival rates were 92.3%, 80.8% and 76.9% in the RP group and 96.6%, 85.4% and 85.4% in the RO group, respectively(P = 0.574). When the initial isoagglutinin titers < 16, neither group showed a rebound rise of isoagglutinin titers. For patients with initial isoagglutinin titers ≥ 16, the rebound rise of isoagglutinin titers was more prominent in the RP group. There was no difference in time-dependent changes in B cell subpopulations and ABO-I-related complications.Conclusions: Sufficient desensitization for ABO-I living donor liver transplantation can be achieved using rituximab alone. This desensitization strategy does not affect the isoagglutinin titers, ABO-I-related complications and patient survival.

Conversion of twice-daily to once-daily tacrolimus is safe in stable adult living donor liver transplant recipients

Once-daily extended-release tacrolimus （Tac-OD） has been introduced as a useful therapeutic option to increase patient adherence to immunosuppressive therapy. This study aimed to evaluate the safety, efficacy and immunosuppressant adherence of conversion from twice-daily tacrolimus （Tac-BID） to Tac-OD in stable adult living donor liver transplant （LDLT） recipients in a single institution. METHODS： Between February and May 2013, Tac-BID was converted to Tac-OD in recipients followed up for at least 12 months after transplantation and without previous rejection episodes. The switching policy was based on a dose ratio of 1：1 with dose adjustment target trough levels at 3-5 ng/mL. Tacro- limus trough levels, laboratory parameters, metabolic disor- ders, and adverse events were assessed. RESULTS： A total of 229 patients were enrolled in the study. The median age at conversion was 53 years （range 31-73）. The median transplant duration was 35.3 months （range 12.0-95.4）. During a median follow-up of 13.5 months after conversion, 9 patients returned to Tac-BID because of adverse events. No acute rejection episodes were observed. Of 214 patients still on Tac-OD at 12 months, 12 （5.6%） received a reduced dose and 95 （44.4%） required an increased dose over baseline. Overall adherence was 82.2% at the end of follow-up. CONCLUSION： The conversion from Tac-BID to Tac-OD with similar target trough levels after conversion is safe and effec- tive for long-term stable LDLT patients.

Proposal of new expanded selection criteria using total tumor size and ^(18)F-fluorodeoxyglucose- positron emission tomography/computed tomography for living donor liver transplantation in patients with hepatocellular carcinoma:The National Cancer Center K

AIM: To expand the living donor liver transplantation(LT) pool of eligible patients with hepatocellular carcinoma(HCC) using new morphological and biological criteria.METHODS: Patients with HCC who underwent living donor LT(LDLT) from March 2005 to May 2013 at the National Cancer Center Korea(NCCK) were enrolled. We performed the 18F-fluorodeoxyglucose positron emission tomography/computed tomography(PET/CT)before LDLT. Overall and disease-free survival analysis was done in patients to evaluate the usefulness of new NCCK criteria using PET/CT and total tumor size(10 cm).RESULTS: We enrolled a total of 280 patients who pathologically confirmed to have HCC and performed the PET/CT before transplantation. Among them, 164(58.6%) patients fulfilled the NCCK criteria and 132 patients(47.1%) met the Milan criteria. Five-year overall and disease-free survival rates for patients who fulfilled the NCCK criteria showed 85.2% and 84.0%, respectively, and were significantly higher than those beyond the NCCK criteria(60.2% and 44.4%, respectively; P < 0.001). The correlation analysis between preoperative imaging tests and pathologic reports using Cohen's Kappa demonstrated the better results in the NCCK criteria than those in the Milan criteria(0.850 vs 0.583). The comparison of diseasefree analysis among the NCCK, Milan, and University of California, San Francisco(UCSF) criteria using the receiver operating characteristics curves revealed the similar area under the curve value criteria(NCCK vs Milan, P = 0.484; NCCK vs UCSF, P = 0.189 at 5-years).CONCLUSION: The NCCK criteria using hybrid concept of both morphological and biological parameters showed an excellent agreement between preoperative imaging and pathological results, and favorable survival outcomes. These new criteria might select the optimal patients with HCC waiting LDLT and expand the selection pool.

Pushing the frontiers of living donor right hepatectomy

Living donor right hepatectomy (LDRH) is currently the most common donor surgery in adult-to-adult living donor liver transplantation although the morbidity and mortality reported in living donors still contradicts the Hippocratic tenet of &#x0201c;do no harm&#x0201d;. Achieving low complication rates in LDRH remains a matter of major concern. Living donor surgery is performed worldwide as an established solution to the donor shortage. The aim of this study was to assess the current status of LDRH and comment on the future of the procedure; assessment was made from the standpoint of optimizing the donor selection criteria and reducing morbidity based on both the authors&#x02019; 8-year institutional experience and a literature review. New possibilities have been explored regarding selection criteria. The safety of living donors with unfavorable conditions, such as low remnant liver volume, fatty change, or old age, should also be considered. Abdominal incisions have become shorter, even without laparoscopic assistance; upper midline laparotomy is the primary incision used in more than 400 consecutive LDRHs in the authors&#x02019; institution. Various surgical techniques based on preoperative imaging technology of vascular and biliary anomalies have decreased the anatomical barriers in LDRH. Operative time has been reduced, with low blood loss. Laparoscopic or robotic LDRH has been tried in only a few selected donors. The LDRH-specific, long-term outcomes remain to be addressed. The follow-up duration of these studies should be long enough to address possible late complications. Donor safety, which is the highest priority, is ensured by three factors: preoperative selection, intraoperative surgical technique, and postoperative management. These three focus areas should be continuously refined, with the ultimate goal of zero morbidity.

Pretransplant absolute monocyte count in peripheral blood predicts posttransplant tumor prognosis in patients undergoing liver transplantation for hepatocellular carcinoma

BACKGROUND: Preoperative absolute monocyte count in peripheral blood(AMCPB) is closely associated with prognoses in not only various malignancies but also hepatocellular carcinoma(HCC). The purpose of this study was to evaluate whether pretransplant AMCPB predicts posttransplant outcomes in patients with HCC undergoing liver transplantation(LT).METHOD: We retrospectively analyzed relationships between clinicopathologic factors involving pretransplant AMCPB and tumor recurrence or survival in 256 patients who had undergone LT for HCC between January 2005 and April 2012.RESULTS: ROC curve analysis showed that AMCPB >200/mm3was a risk factor for tumor recurrence; 43 patients showed higher AMCPB(>200/mm3), whereas 213 showed lower AMCPB(≤200/mm3) at the time of LT. On multivariate analysis,pretransplant high AMCPB, positive findings in pretransplant18F-FDG PET/CT, pathological maximal tumor size >5 cm,intrahepatic metastasis, moderately or poorly differentiated tumor and microvascular invasion were independent factors affecting recurrence-free survival. When we performed subgroup analysis based on the Milan criteria, high AMCPB was an independent factor for predicting HCC recurrence in patients with tumor beyond the Milan criteria(P=0.004), and not for patients within the criteria.CONCLUSION: This study demonstrated that pretransplant AMCPB could predict tumor recurrence after LT for HCC,especially in patients with tumor beyond the Milan criteria.

Right hepatectomy in living donors with previous abdominal surgery

BACKGROUND： Few studies have evaluated the impact of previous abdominal surgery （PAS） on living donor right hepatectomy （LDRH）. The aim of this study was to investigate the outcomes of liver transplantation using right lobe grafts of living donors with PAS. METHODS： Data were reviewed from LDRH patients at the authors＇ institution between March 2008 and November 2014. LDRH patients with PAS were divided into two groups according to upper PAS （group 1） or lower PAS （group 2）, and they were compared to those without PAS （group 3） who were matched 1：1 based on age, gender, and body mass index. Periop- erative data, complications by the Clavien classification, and the outcomes with more than 14 months follow-up were compared. RESULTS： Twenty-three （4.9%） of a total of 471 LDRH donors had PAS. Eleven donors were assigned to group 1, 12 to group 2, and 23 to group 3. Intraperitoneal adhesions were found in 20 （87.0%） of 23 donors with PAS, of whom 5 （21.7%） had adhesiolysis-related injuries that happened more commonly in group 1 than in group 2 （P=0.025）. LDRH was successfully completed under upper midline laparotomy in all donors. No donors received perioperative blood transfusion. The peak postoperative AST, ALT, INR, and total bilirubin levels made no difference between the three groups. Compared with group 3, groups 1 and 2 had a longer operative time （P=0.012） and a higher grade I complication rate （P=0.047）. All donors recovered fully to their routine activities. The 23 recipients of grafts from donors with PAS showed good liver function with 1-year graft and patient survivals of 100%. CONCLUSION： A history of PAS is not a contraindication to LDRH in the current era of advanced surgical techniques.

Successful living donor liver transplantation with a graft-to-recipient weight ratio of 0.41 without portal flow modulation:A case report

BACKGROUND There have been numerous efforts to lower the limit of minimum graft size to meet the metabolic demand of recipients in adult-to-adult living donor liver transplantation(LDLT).We experienced a successful case of LDLT using a verysmall-for-size graft without portal flow modulation such as splenectomy or portocaval shunt.CASE SUMMARY A 49-year-old man(weighing 91 kg)suffering hepatocellular carcinoma accompanied with hepatitis B virus related cirrhosis underwent LDLT.The one and only voluntary donor was his 17-year-old daughter whose body weight was 50 kg with a body mass index(BMI)of 18.3.The procured right liver graft was 411 g with a real graft-to-recipient weight ratio(GRWR)of 0.41%,the smallest to be reported in the literature.Both the recipient and donor had an uneventful recovery and were discharged on days 15 and 8,respectively,with normal liver function.The father and daughter have had no complication so far and are still in good health with normal liver function 81 mo after LDLT.CONCLUSION Satisfactory outcomes can be achieved in LDLT with a GRWR as low as 0.41%even without using portal flow modulation in highly selected patients.

Arterial blood gas test to decide whether to reconstruct single or both the arteries in living donor liver transplantation

Background:The graft used in living donor liver transplantation(LDLT)sometimes has two hepatic arteries.This study aimed to introduce arterial-blood gas(ABG)test on the decision on whether to reconstruct a single or both arteries in LDLT.Methods:Patients with a right lobe graft with two hepatic arteries were enrolled from the prospectively maintained database of our institution.After anastomosis of one of two arteries,the back-bleeding from the second hepatic artery was taken for ABG test.Depending on the results,the second artery was anastomosed or ligated.Results:Between January 2012 and December 2017,a total of 372 patients underwent LDLT,and 21 living donors had two right hepatic arteries.Based on ABG test results,a single anastomosis was created in 15 recipients while double anastomoses were performed in the remaining 6 recipients.All the patients had an uneventful recovery and were discharged in good conditions.Neither hepatic artery thrombosis nor liver dysfunction was observed during the median follow-up of 26 months(range,6–71 months).The overall incidence of biliary complications was 9.5%(2/21).Bile leakage arose in one patient with two hepatic artery reconstructions,and the patient subsequently developed biliary stricture.Biliary stricture occurred in another patient with one hepatic artery reconstruction.The biliary complications were successfully managed with endoscopic or percutaneous intervention.Conclusions:ABG test provides a good measure for deciding whether to reconstruct single or both arteries in LDLT.

Gastroepiploic arteriovenous shunt as a salvage treatment for hepatic artery occlusion after living donor liver transplantation

Hepatic artery occlusion(HAO)is a calamitous vascular complication following living-donor liver transplantation(LDLT)leading to graft loss with a high mortality(1).Re-transplantation is considered when revascularization fails,but may impose heavy burdens in terms of donor shortage and ultra-major surgery.

Giant hepatic neuroendocrine tumor

A 47-year-old female was presented with progressive abdominal distension and dyspnea for 2 years.Her height was 152.3 cm and body weight was 53.9 kg.She was completely confined to bed and could not perform any selfcare tasks.The serum total bilirubin level was 6.4 mg/dL.Radiologic imaging showed multiple hepatic tumors involving a whole liver and compressing inferior vena cava and other organs(Panel A).

Pretransplant locoregional therapy for hepatocellular carcinoma:encouraging but insufficient

Despite in the era of liver transplantation(LT)widely performed as an established curative treatment for hepatocellular carcinoma(HCC),the scarcity of liver donors has still been a well-nigh insurmountable barrier to access of LT.So,the bridging locoregional therapy(LRT)that treats HCC during the waiting time prior to LT emerged as an attractive strategy to reduce the risk of tumor progression and waitlist dropout,which came to an international consensus statement regarding the waitlist management of HCC patients(1).However,the actual advantage for LRT has not been clearly demonstrated in terms of recurrence and survival.