Liver transplantation for combined hepatocellular carcinoma and cholangiocarcinoma: A multicenter study.

BACKGROUND: Patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) are not traditionally considered eligible for liver transplantation (LT) due to poor outcomes. AIM: To compare outcomes between living donor LT (LDLT) patients with hepatocellular carcinoma (HCC) and LT patients with cHCC-CC and to identify risk factors for tumor recurrence and death after LT in cHCC-CC patients. METHODS: Data for pathologically diagnosed cHCC-CC patients (n = 111) who underwent LT from 2000 to 2018 were collected for a nine-center retrospective review. Patients (n = 141) who received LDLT for HCC at Samsung Medical Center from January 2013 to March 2017 were selected as the control group. Seventy patients in two groups, respectively, were selected by 1:1 matching. RESULTS: Cumulative disease-free survival (DFS) and overall survival (OS) in the cHCC-CC group were significantly worse than in the HCC group both before and after matching. Extrahepatic recurrence incidence in the cHCC-CC group was higher than that in the HCC group (75.5% vs 33.3%, P < 0.001). Multivariate analysis demonstrated that the cHCC-CC group had significantly higher rates of tumor recurrence and death compared to the HCC group. In cHCC-CC subgroup analysis, frequency of locoregional therapies > 3, tumor size > 3 cm, and lymph node metastasis were predisposing factors for tumor recurrence in multivariate analysis. Only a maximum tumor size > 3 cm was a predisposing factor for death. CONCLUSION: The poor prognosis of patients diagnosed with cHCC-CC after LT can be predicted based on the explanted liver. Frequent regular surveillance for cHCC-CC patients should be required for early detection of tumor recurrence.

Ghost-Free Deep High-Dynamic-Range Imaging Using Focus Pixels for Complex Motion Scenes.

Multi-exposure image fusion inevitably causes ghost artifacts owing to inaccurate image registration. In this study, we propose a deep learning technique for the seamless fusion of multi-exposed low dynamic range (LDR) images using a focus-pixel sensor. For auto-focusing in mobile cameras, a focus-pixel sensor originally provides left (L) and right (R) luminance images simultaneously with a full-resolution RGB image. These L/R images are less saturated than the RGB images because they are summed up to be a normal pixel value in the RGB image of the focus pixel sensor. These two features of the focus pixel image, namely, relatively short exposure and perfect alignment are utilized in this study to provide fusion cues for high dynamic range (HDR) imaging. To minimize fusion artifacts, luminance and chrominance fusions are performed separately in two sub-nets. In a luminance recovery network, two heterogeneous images, the focus pixel image and the corresponding overexposed LDR image, are first fused by joint learning to produce an HDR luminance image. Subsequently, a chrominance network fuses the color components of the misaligned underexposed LDR input to obtain a 3-channel HDR image. Existing deep-neural-network-based HDR fusion methods fuse misaligned multi-exposed inputs directly. They suffer from visual artifacts that are observed mostly in saturated regions because pixel values are clipped out. Meanwhile, the proposed method reconstructs missing luminance with aligned unsaturated focus pixel image first, and thus, the luma-recovered image provides the cues for accurate color fusion. The experimental results show that the proposed method not only accurately restores fine details in saturated areas, but also produce ghost-free high-quality HDR images without pre-alignment.

En Bloc Kidney Transplant From a Pediatric Donor to a Pediatric Recipient Through a Total Extraperitoneal Approach: A Case Report.

En bloc kidney transplant remains a technically challenging procedure, especially in pediatric transplants. The intra-abdominal approach has been the preferred operation for very young children. However, the transverse incision could result in more abdominal muscle damage and intra-abdominal adhesions. If the extraperitoneal approach, which is the standard method for adult kidney transplant, could be performed in pediatric recipients, then adverse effects after a transverse incision could be avoided. A 30-month-old female recipient (13.1 kg) underwent an en bloc kidney transplant from a 36-month-old female donor (13.3 kg) who had cardiac arrest of unknown origin. The kidneys were retrieved with the en bloc technique using a bladder patch. A right Gibson incision was made along the lateral fascia of the rectus muscle of the recipient to prevent muscle fiber damage. The inferior vena cava and aorta of the donor were anastomosed to the inferior vena cava and right common iliac artery of the recipient, respectively. The bladder patch with 2 ureteral openings was directly anastomosed to the bladder of the recipient. Urination was excellent immediately after the operation. The recipient recovered quickly. The total extraperitoneal approach is feasible and has some advantages over the transverse incision, even in pediatric recipients.

Ambient light robust gamut mapping for optical see-through displays.

An optical see-through (OST) display is affected more severely by ambient light than any other type of displays when placed in an outdoor environment with bright illuminance because of its transparency and thus, its inherent color distortion can worsen. It is hard to directly apply existing gamut mapping methods to an OST display because of its morphological gamut characteristic and the effect of ambient light. In this paper, we propose a new robust gamut mapping method which works against bright ambient light. The process is divided into two steps: lightness mapping (LM) and chroma reproduction. LM aligns the lightness level of sRGB gamut with OST gamut and partitions the region of OST gamut based on the relative size of the sRGB gamut and its lightness value. The second step (chroma reproduction) determines an appropriate chroma reproduction method (gamut compression or extension) and a proper direction for gamut mapping based on the characteristics of each region in order to minimize the effects of ambient light. The quality of color reproduction is qualitatively and quantitatively evaluated based on accurate measurements of the displayed colors. It has been experimentally confirmed that the proposed gamut mapping method can reduce color distortion more than the existing parametric gamut mapping algorithms.

Bloodless living donor liver transplantation: Risk factors, outcomes, and diagnostic predictors.

Massive bleeding is often unavoidable during liver transplantation (LT). However, blood transfusions are associated with risks and should be avoided whenever possible. This study compares preoperative factors and outcomes between non-transfusion and transfusion groups to identify variables that could be used to predict bloodless surgery in living donor liver transplantation (LDLT) patients.We conducted a retrospective study of 87 LDLT patients. The group of patients who did not require packed red blood cell (PRBC) transfusion (non-PRBC group, n = 44) was compared with those who did (PRBC group, n = 43). We compared risk factors, fluid management, and outcomes between the groups and identified variables for prediction of transfusion during LDLT.Compared with the PRBC group, the non-PRBC group had a lower model for end-stage liver disease (MELD) score (8.1 ±â€Š1.1 vs 18.2 ±â€Š8.8), international normalized ratio (INR) (1.16 ±â€Š0.1 vs 1.80 ±â€Š0.94), and partial thromboplastin time (PTT) (37.1 ±â€Š6.3 vs 54.1 ±â€Š24.0), but higher hemoglobin (Hb) (13.6 ±â€Š1.6 vs 11.5 ±â€Š2.2) and hematocrit (HCT) (39.1 ±â€Š4.4 vs 32.6 ±â€Š6.0). The non-PRBC group were more likely to receive colloid and albumin but had shorter intensive care unit (ICU) and hospital length of stay. The area under the receiver operative characteristic (ROC) curve of the MELD score was the highest (91%) using a cutoff value of 10.5.Patients without PRBC transfusion during LDLT were in better condition preoperatively and had better outcomes. The MELD score is a significant predictor for PRBC transfusion.

Caudal middle hepatic vein trunk preserved right lobe graft in living donor liver transplantation.

PURPOSE: Multiple segment 5 vein (V5) anastomoses are common and inevitable in living donor liver transplantation (LDLT) using modified right lobe (MRL) graft. Sacrifice of segment 4a vein (V4a) can simplify bench work and avoid graft congestion. But it could be harmful to some donors in previous simulation studies. This study aimed to evaluate donor safety in LDLT using caudal middle hepatic vein trunk preserved right lobe (CMPRL) graft. METHODS: LDLT using MRL grafts were performed on 33 patients (group A) and LDLT using CMPRL grafts were performed on 37 patients (group B). Group B was classified into 2 subgroups by venous drainage pattern of segment 4: V4a dominant drainage group (group B1) and the other group (group B2). Parameters compared between group A donors and group B donors included operation time, bench work time, number and diameter of V5, remnant liver volume and postoperative course. Those were also investigated in group B1 compared with group B2. And, we reviewed postoperative course of the recipients in groups A and B. RESULTS: Operation time and bench work time in group B were significantly shorter. There were no significant differences in most postoperative parameters between groups B1 and B2. As a result of recipient, V5 patency rates after LDLT were significantly higher in group B. CONCLUSION: LDLT using CMPRL graft is a safe procedure for living donors. Donors with any type of V4 could be proper candidates for CMPRL graft if remnant liver volume is greater than 30% with minimal fatty change.

Asiatic acid derivatives protect primary cultures of rat hepatocytes against carbon tetrachloride-induced injury via the cellular antioxidant system.

We attempted to elucidate the hepatoprotective mechanism of two asiatic acid (AS) derivatives, 3beta,23-dihydroxyurs-2-oxo-12-ene-28-oic acid (AS-10) and 3beta,23-dihydroxyurs-12-ene-28-oic acid (AS-14), which exhibited significant protective activity against carbon tetrachloride (CCl4)-induced hepatotoxicity in primary cultures of rat hepatocytes. Our findings showed that AS-10 and AS-14 preserved the level of glutathione and the activities of antioxidant enzymes such as glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase. In addition, these compounds ameliorated lipid peroxidation, as demonstrated by a reduction in the production of malondialdehyde. Furthermore, AS-10 and AS-14 did not restore the reduced total GSH level by BSO, indicating that the hepatoprotective activities of these compounds may be involved, in part, by regulating GSH synthesis. From these results, we suggest that both AS-10 and AS-14 exerted their hepatoprotective activities against CCl4-induced injury by preserving the cellular antioxidative defense system.

Technique and outcome of autologous portal Y-graft interposition for anomalous right portal veins in living donor liver transplantation.

This study was intended to describe in detail the surgical technique and long-term outcome of autologous portal vein (PV) Y-graft interposition for adult living donor liver transplantation (LDLT). We assessed the outcome of 841 patients who underwent right lobe LDLT from January 2002 to December 2007 with respect to the reconstruction of double-graft PVs. PV anatomy of the donor livers was classified as type I in 796 patients (94.6%), type II in 15 patients (1.8%), and type III in 30 patients (3.6%). Seven type II grafts and all type III PV grafts had double PV orifices. Autologous PV Y-graft interposition was used in 31 patients, and complications occurred in only 1 patient during a median follow-up of 27 months. Overall, the 1- and 3-year graft survival rates were 87.5% and 80.6%, respectively. Use of a Y-graft was not a risk factor for biliary complications, but the liver anatomy of anomalous PV per se seems to be associated with a higher occurrence of biliary complications, especially during the early posttransplant period. The favorable outcome and technical feasibility of autologous portal Y-graft interposition imply that this technique could be the standard procedure for reconstruction of right lobe grafts with double PV orifices.

Transjugular liver biopsy in patients with living donor liver transplantation: comparison with percutaneous biopsy.

Transjugular liver biopsy (TJLB) is an alternative method of pathological diagnosis in patients with an established contraindication to percutaneous biopsy. Between November 2005 and July 2007, 111 TJLBs were attempted in 67 patients and 95 percutaneous liver biopsies (PCLBs) were attempted in 51 patients with living donor liver transplantation suspected of having rejection. Indications of TJLB included classic contraindications to PCLB and a postoperative period of less than 30 days. TJLB was performed a mean of 111.1 +/- 292.6 days after transplantation (range: 6-2478 days, median: 35 days), and PCLB was performed a mean of 534.7 +/- 591.6 days after transplantation (range: 6-2555 days, median: 299 days). Technical success was 99.1% in TJLB and 100% in PCLB, and there was no significant difference between these 2 groups (P = 0.354). A clinical suspicion of rejection was confirmed by histopathology in 38 (34.2%) of 111 TJLBs and 38 (40.0%) of 95 PCLBs. The overall complication rates related to the procedure were 1.8% (2/111) in TJLB and 5.3% (5/95) in PCLB. Although there was no significant difference in complication rates between TJLB and PCLB (P = 0.172), the patients who underwent TJLB showed significantly higher incidence of ascites, coagulopathy, and thrombocytopenia, given its indication. TJLB seems to be a safe and effective procedure for pathological diagnosis of rejection in patients with living donor liver transplantation when there is a high risk of complication with PCLB.

Prevention of hepatitis B recurrence after living donor liver transplantation: primary high-dose hepatitis B immunoglobulin monotherapy and rescue antiviral therapy.

The prevention of hepatitis B virus (HBV) recurrence is essential after liver transplantation in patients infected with HBV. We evaluated the efficacy of primary high-dose hepatitis B immunoglobulin (HBIG) monotherapy and rescue antiviral therapy in 639 HBV-infected adult patients who underwent living donor liver transplantation (LDLT) between February 1997 and December 2004. The overall 5-year survival rate was 80.7%, and recurrence of hepatocellular carcinoma was the most common cause of late mortality. Pretransplant HBV replication was observed in 392 (61.3%) patients. The interval of 10,000-IU HBIG administration to maintain antibody to hepatitis B surface antigen > 500 IU/L was 30 days in 11.4% patients, 40 to 50 days in 72.1%, and 60 days in 16.5%. At the last follow-up, 3.9% of the patients without HBV recurrence were receiving combination therapy. Overall 1-year, 3-year, 5-year, and 10-year HBV recurrence rates were 1.4%, 5.5%, 7.3%, and 8.5%, respectively. HBV recurrence occurred after a mean of 25.7 +/- 16.4 months after LDLT. After HBV recurrence, 5 of 9 patients died from rapidly progressive liver failure before treatment with adefovir, and only 1 of 29 patients died after treatment with adefovir. Need for frequent HBIG infusions (< or =30 days), active pretransplant HBV replication, and hepatocellular carcinoma recurrence were significant risk factors for HBV recurrence and indications for combination therapy. Our posttransplant HBV prophylaxis regimen resulted in a 5-year HBV recurrence rate of 7.3% and a mortality rate of 13.2% after HBV recurrence, showing the effectiveness of high-dose HBIG monotherapy and rescue antiviral therapy.

Technical modification of reno-portal anastomosis in living donor liver transplantation for patients with obliterated portal vein and large spontaneous splenorenal shunts.

BACKGROUND/AIMS: End-stage liver disease patients with obliterated portal vein(PV) and large spontaneous splenorenal shunts (SRS) are often indicated to renoportal bypass as a reconstruction of portal inflow during liver transplantation. The aim of this study was to show the feasibility and safety of the side-to-end (S-to-E) renoportal anastomosis (RP-A). METHODOLOGY: RP-A were performed in 5 patients among 597 adult living donor liver transplantation (LDLT) with end-to-end (E-to-E) or S-to-E method interposing cadaveric fresh vessel grafts between left renal vein (LRV) and PV of liver graft from October 2005 to June 2008. RESULTS: One patient underwent E-to-E RP-A, but it was technically difficult in our experience because of thin and retracted renal vein end under poor operation field. Remaining four patients underwent side-to-end (S-to-E) RP-A which allowed us to perform easy and secure anastomosis under better and more stable operation field, because LRV continuity with vena cava was preserved without retraction of anastomosis site. Except one patient having two left-lobes dual-graft LDLT who died from cerebral hemorrhage, four patients were recovered well with normal graft function and a patent RP-A. CONCLUSIONS: S-to-E anastomosis is technically more feasible and easier method than E-to-E anastomosis for RP-A interposing cadaveric fresh vessel in LDLT.

Radical surgical resection for carcinoid tumors of the ampulla.

Ampullary carcinoid tumors are extremely rare. The present study describes the clinicopathological features and outcomes for 10 ampullary carcinoid patients who underwent radical resection from 1998 to 2005. During this study period, 294 patients underwent pancreatoduodenectomy for ampullary neoplasms in our institution. The mean patient age was 58.0 +/- 13.4 years, and seven were male. Initial clinical manifestations were jaundice in four patients, nonspecific gastrointestinal symptoms in five, and completely asymptomatic in one. Standard pancreatoduodenectomy was performed in three patients, and pylorus-preserving pancreatoduodenectomy in seven, and there were no major complications. The mean tumor size and volume were 2.1 +/- 1.3 cm and 4.1 +/- 6.9 ml, respectively. Synaptophysin staining was positive in ten patients and chromogranin staining positive in eight. R0 resection was achieved in all ten patients. Overall and disease-free survival rates were 90 and 80% at 1 year, and 64 and 56% at 3 years, respectively. The liver was the most common site of initial metastasis after curative resection. Univariate analyses revealed that a maximal tumor diameter > or =2 cm and tumor extension beyond the ampulla were risk factors for tumor recurrence. In conclusion, while the majority of ampullary carcinoids are indolent, this tumor is associated with a relatively poor prognosis. We believe that radical resection, with the aim of complete tumor removal and cure, is the treatment of choice.

SK-126, a synthetic compound, regulates the production of inflammatory cytokines induced by LPS in antigen-presenting cells.

A variety of mediators released by immune cells triggers or enhances specific aspects of the inflammatory response. Dendritic cells (DCs) play an essential role in the innate immune system by shaping the adaptive immune responses and by controlling the production of cytokines in response to inflammatory stimuli. In the present study, we investigated whether SK-126, a pyridine derivative based on gentianine originated from a natural product, can affect the LPS-induced inflammatory cytokine production in DC. Interestingly, treatment of mouse bone marrow-derived dendritic cells (BMDCs) and the murine dendritic cell line, DC 2.4, with SK-126 completely suppressed LPS-induced TNF-alpha expression at both transcriptional and protein levels. In contrast to TNF-alpha, SK-126 enhanced IL-10 expression at both transcriptional and protein levels. To determine signaling pathways involved in the regulation of inflammatory cytokines, we examined the involvement of MAPK and the transcription factor, NF-kappaB. SK-126 enhanced ERK1/2 and p38 activation following LPS stimulation, but it did not induce phosphorylation of SAPK/JNK and NF-kappaB. Also, STAT3 phosphorylation after LPS stimulation was increased by SK-126 to a large extent. Using specific inhibitors, we confirmed that SK-126 has dual effects in which it suppresses TNF-alpha production and enhances IL-10 production via the up-regulation of ERK1/2 and p38. Finally, LPS-induced inflammatory responses such as TNF-alpha production in vivo were significantly reduced by treatment with SK-126. Therefore, our findings suggest that SK-126 may be a useful drug candidate to treat inflammatory diseases in which pro- or anti-inflammatory cytokines play a significant role in their pathogenesis.

Application of intraoperative cine-portogram to detect spontaneous portosystemic collaterals missed by intraoperative doppler exam in adult living donor liver transplantation.

Adequate portal inflow is essential to the regeneration of a partial liver graft after adult living donor liver transplantation (LDLT). A recipient having large spontaneous portosystemic collaterals with or without portal vein (PV) stenosis would require surgical interruption of large collaterals and/or correction of PV stenosis to prevent postoperative "portal flow steal phenomenon." Intraoperative Doppler ultrasound (IOUS) has been used to estimate the adequacy of portal inflow, but it has a limitation to identify the correct anatomical and hemodynamic parameters of portosystemic collaterals. We initiated to utilize intraoperative cine-portogram (IOCP) to overcome the limitations of IOUS. The spontaneous portosystemic large collaterals in 5 of 156 adult LDLTs from March 2003 to February 2004 were precisely identified not by IOUS but by IOCP, and successfully interrupted. In addition, 3 of these patients had stenotic PV (<1 cm in diameter), which was interfering with the hepatopetal portal flow and the PVs were effectively widened by the placement of intraoperative PV stenting. In conclusion, IOCP seems to be an effective tool for precise detection of the persistent large portosystemic collaterals that were not detected by IOUS, and for monitoring their complete interruption.

Staged surgery for chronic primary aortoduodenal fistula in a septic patient.

Aortoenteric fistula is one of the most challenging problems that confront the vascular surgeons. Controversy remains over the optimal treatment because of the continued publication of series with high mortality, amputation, and aortic disruption rates. A positive preoperative blood culture is the best predictor of mortality with increased amputation rates due to infection of the extra-anatomic bypass. Therefore, in selected cases with sepsis, a prudent management protocol is required. We report a 68-yr-old male presenting with a chronic primary aortoduodenal fistula extensively involving the duodenum and Gram-negative sepsis. We planned a staged operation. Initially, an emergency laparotomy and control of the aorta allowed stabilization of the patient, identification of the fistula, and direct in situ placement of the prosthetic graft followed by an en bloc resection of the aneurysm and the surrounding structures. After he recovered from sepsis and had been stabilized, a staged extra-anatomic bypass followed by transabdominal removal of the temporarily placed graft was done. This management plan will allow the highest success rate and may be a prudent management protocol for these difficult cases.

Synthesis and biological evaluation of 3-(4-substituted-phenyl)-N-hydroxy-2-propenamides, a new class of histone deacetylase inhibitors.

Inhibitors of histone deacetylases (HDACs) have been shown to induce differentiation and/or apoptosis of human tumor cells. Novel 3-(4-substituted-phenyl)-N-hydroxy-2-propenamides have been prepared as a new class of HDAC inhibitors and evaluated for their antiproliferative activity and HDAC inhibitory activity. Incorporation of a 1,4-phenylene carboxamide linker, shown by 5, and a 4-(dimethylamino)phenyl or 4-(pyrrolidin-1-yl)phenyl group as a cap substructure generated highly potent hydroxamic acid-based HDAC inhibitors 5a and 5b.