Neoadjuvant therapy with intensity-modulated radiotherapy combined with S-1 for borderline-resectable pancreatic cancer.

AIM: We evaluated the efficacy of neoadjuvant chemotherapy with intensity-modulated radiotherapy (NAC-IMRT) in patients with borderline-resectable pancreatic cancer (BRPC). METHODS: BRPC patients were treated with IMRT (45 Gy/15fr) combined with two courses of S-1 (40 mg/m2 bid) before surgery. Outcomes after NAC-IMRT, surgery, and survival were then evaluated. This single-center retrospective study assessed 26 consecutive patients. RESULTS: Twenty-six patients (BR-PV: 7, BR-A: 19) with a median age of 73 years were enrolled from 2016 to 2021. Ten (38%) patients were 75-years-old and above. Twenty-three patients completed NAC-IMRT treatment. The median reductions in tumor size and cancer antigen 19-9 level were 13.6% and 69%, respectively. All 26 patients underwent resection within a median time of 71 days after NAC-IMRT initiation. R0 resection was achieved in 24 patients (92%). The median overall survival (OS) was 28.0 months, and the 1- and 3-year OS rates were 100% and 34%, respectively. The median progression-free survival (PFS) was 12.5 months, and the 1- and 3-year PFS rates were 50% and 32%, respectively. No significant differences were observed in OS between the patients under and over the age of 75 (29 vs. 20 months, p = 0.86). The 12 patients who completed NAC-IMRT, resection, and subsequent adjuvant chemotherapy (AC) exhibited a 3-year survival rate of 73%, which was significantly better than that of the patients who did not receive or complete AC (median OS, not reached vs. 19 months, p < 0.001). CONCLUSION: NAC-IMRT showed outstanding clinical efficacy with acceptable tolerability in patients with BRPC, including geriatric patients.

Real-Time Fluorescent Cholangiography by Intrabiliary Indocyanine Green Administration With Near-Infrared Laparoscopy in Major Hepatectomy.

BACKGROUND AND PURPOSE: Biliary injury is a severe complication that can be associated with liver surgery. Intrahepatic biliary anatomy can be evaluated using magnetic resonance cholangiopancreatography and X-ray cholangiography; however, an intraoperative real-time bile duct visualization method has not yet been reported. This study aimed to demonstrate the availability of real-time fluorescent cholangiography (FC) by intrabiliary indocyanine green administration with near-infrared laparoscopy in major hepatectomy. METHODS: The optimal concentration of indocyanine green (ICG) solution was examined ex vivo. The fluorescence intensity of the ICG solution and its mixture with bile was measured. Using a clinical trial model, ICG solution was injected into the cystic duct, followed by near-infrared laparoscopy performed during hepatectomy. RESULTS: The optimal concentration of ICG solution for FC was between 0.01 and 0.05 mg/mL. Three different laparoscopic systems were used in three hepatectomy cases. In all cases, the fluorescence of the intrahepatic bile ducts in the Glissonian sheath was clearly visualized using the near-infrared laparoscopic system. A small piece of tissue prevented the bile glow; thus, exposure of the Glissonian sheath was necessary for clear FC. This procedure also detected bile leakage from the cut surface of the liver. CONCLUSIONS: Intrabiliary ICG administration and near-infrared laparoscopy enabled real-time intrahepatic FC during major hepatectomy.

A novel method of anvil placement of circular stapler for esophagojejunostomy in laparoscopic total gastrectomy for gastric cancer: results of consecutive 200 cases.

BACKGROUND: Laparoscopic total gastrectomy for gastric cancer is still a demanding operation because of technical difficulties, especially of intracorporeal esophago-jejunal anastomosis. METHODS: We introduced a newly designed method of anvil placement of circular stapling devices (CS) for laparoscopic esophagojejunostomy (EJS). A small incision was made on the anterior wall of the stomach, from which the anvil was inserted into the stomach and proceeded to the thoracic esophagus. Then, the abdominal esophagus was transected by a linear stapler, and the anvil into the esophagus was drawn back to the esophageal stump by pulling out the cotton tape pre-attached to the anvil. Intracorporeal EJS by Roux-en-Y reconstruction was performed by CS inserted into the abdominal cavity from the umbilical wound. RESULTS: A total of consecutive 200 gastric cancer patients underwent laparoscopic total gastrectomy using this method. There was no operative mortality. Anastomotic complications occurred in 12 cases (6.0%): 9 cases of stenosis (4.5%) and 3 cases of bleedings (1.5%). Anastomotic leakage was not observed. As for non-anastomotic complications, there occurred 2 pulmonary complications (1.0%), 3 pancreatic leakages (1.5%), and 8 bowel obstructions due to internal hernia (4.0%). With a median follow-up period of 47.1 months, 5-year overall survival for assessable patients (n = 193) was 60.3% (95% CI 52.6-67.2). The total rate of peritoneal recurrence was 9.8%. CONCLUSION: Our new method of anvil placement for laparoscopic EJS with CS is safe and feasible with favorable survival outcomes. It eliminates the need for suturing, and will promote the clinical application of laparoscopic total gastrectomy for gastric cancer. CLINICAL TRIALS: UMIN000046119.

Re-do laparoscopic esophagojejunostomy for anastomotic stenosis after laparoscopic total gastrectomy in gastric cancer.

PURPOSE: Anastomotic stenosis of esophagojejunostomy after total gastrectomy has a substantial impact on the postoperative quality of life of the patient. If conservative treatment doesn't work, surgical intervention should be considered. However, redoing esophagojejunostomy is an extremely demanding procedure. Especially in the case where the primary surgery was performed laparoscopically, it is an unmet problem to maintain minimal invasiveness in re-do surgery. METHODS: We report 3 cases of re-do esophagojejunostomy laparoscopically performed for anastomotic stenosis after laparoscopic total gastrectomy in gastric cancer, in whom endoscopic balloon dilation did not work. RESULTS: Each patient underwent a re-do esophagojejunostomy laparoscopically. The mean operation time was 293 min, and the mean blood loss was 56 ml. There was no anastomosis-related complication, and they were discharged from hospital on 11-16 postoperative days. At the time of discharge, oral food intake was 100% in each patient. One year after the operation, follow-up endoscopic exams showed no anastomotic stenosis. CONCLUSION: Re-do laparoscopic esophagojejunostomy for anastomotic stenosis after laparoscopic total gastrectomy was safely and successfully performed. It brings patients minimal invasiveness continuously from the initial surgery. Re-do laparoscopic esophagojejunostomy could be one of the options for anastomotic stenosis resistant to conservative treatment.

Long-term efficacy and risk factors for stent occlusion in portal vein stent placement: a multi-institutional retrospective study.

BACKGROUND: Surgical treatment for PV (portal vein) stenosis/occlusion can pose a fatal risk of massive bleeding from severe adhesions and collateral vessel formation. PV stents placement is a minimally invasive and effective procedure for PV stenosis/occlusion, but PV stents sometimes occlude. The relationship between post-stent PV hemodynamics and stent occlusion has not been thoroughly investigated. Certain precautions during PV stent placement may reduce the risk of stent occlusion. This study aimed to evaluate long-term outcomes of PV stent patency and investigate factors including PV hemodynamics associated with stent occlusion. MATERIALS AND METHODS: Thirty-four consecutive patients with PV stenosis/occlusion who underwent PV stent placement in four institutions between December 2006 and February 2021 were retrospectively examined. The primary study endpoints were technical success, clinical success, and cumulative stent patency rate. The secondary endpoints were risk factors of stent occlusion. A univariable Cox proportional hazards model with sixteen variables was used to determine predictors of stent occlusion. Factors with p-value ≤ 0.1 in univariable analysis were included in the multivariable analysis. Alpha was set at 0.05. RESULTS: Technical and clinical success rates were 88.2% and 79.4%, respectively. Six patients (17.7%) experienced stent occlusion. The cumulative stent patency rate at six months, one year, and three years was 79.1%, 79.1%, and 65.9%, respectively. In the univariate analysis, the variables with p-value ≤ 0.1 were lesion length > 4 cm, hepatofugal collateral vein visualization after stent placement, and residual stenosis > 30% after stent placement. In the multivariate analysis, residual stenosis > 30% after stent placement was significantly associated with stent occlusion (hazard ratio, 10.80; 95% confidence interval, 1.08-108.44; p = 0.04). CONCLUSION: PV stent placement was technically feasible and effective in improving portal hypertension. However, stent occlusion was not uncommon. Residual stenosis > 30% after stent placement was significantly associated with stent occlusion. We should pay attention to correctly assess the range of stenosis and release the stenosis as much as possible.

A case of a renal abscess caused by Salmonella bareilly in a previously healthy boy.

BACKGROUND: Renal abscesses are relatively uncommon in children, and usually due to Gram-negative rods or Staphylococcus aureus, whereas abscesses caused by Salmonella are very rare. CASE PRESENTATION: We present the case of a previously healthy 10-year-old boy who had a renal abscess due to Salmonella bareilly. He responded well to treatment with antibiotics, and computed tomography (CT)-guided drainage of the abscess. His blood, urine and abscess aspirate cultures were sterile, but a broad-range 16S rDNA polymerase chain reaction (PCR) assay of the aspirate followed by analysis of four Salmonella genes (fliC, fliD, sopE2, and spaO) identified S. bareilly as the causative agent. CONCLUSION: To the best of our knowledge, this is the first report of renal abscess caused by S. bareilly.

Intrahepatic bile duct rupture associated with IgG4-related sclerosing cholangitis presenting hepatic inflammatory pseudotumor.

A 67-year-old man with a low-grade fever was found to have a 25-mm diameter tumor of the left hepatic umbilical portion. The tumor was accompanied by occlusion of the left portal vein. Positron emission tomography using fluorodeoxyglucose showed that the tumor had abnormally high metabolic activity. Magnetic resonance imaging revealed the left hepatic duct segmental narrowing. There was a mild elevation in serum IgG4 (206 mg/dL). Intrahepatic cholangiocarcinoma was suspected. Instead of planned hepatectomy, the patient was forced to undergo emergency surgery for biliary panperitonitis caused by intrahepatic bile duct rupture. Intraoperative ultrasonography revealed a hypoechoic tumor-like thickened Glissonean sheath and needle biopsy was performed. Histologic examination confirmed fibrous tissue with IgG4-positive plasma cell infiltration without neoplastic proliferation. He was diagnosed with IgG4-related sclerosing cholangitis (IgG4-SC) presenting hepatic inflammatory pseudotumor. After his general condition improved, he underwent left hepatectomy. Macroscopic findings showed extreme fibrosis of the Glissonean sheath of the umbilical portion, and diffuse granular lesion aggregated in the left lateral segment. Microscopic examination confirmed chronic cholangitis and dense portal fibrosis in the umbilical portion and diffuse xanthogranulomatous inflammation. This is the first case report of spontaneous rupture of the intrahepatic bile duct in patient with IgG4-SC.

CRL4DCAF1/VprBP E3 ubiquitin ligase controls ribosome biogenesis, cell proliferation, and development.

Evolutionarily conserved DCAF1 is a major substrate receptor for the DDB1-CUL4-ROC1 E3 ubiquitin ligase (CRL4) and controls cell proliferation and development. The molecular basis for these functions is unclear. We show here that DCAF1 loss in multiple tissues and organs selectively eliminates proliferating cells and causes perinatal lethality, thymic atrophy, and bone marrow defect. Inducible DCAF1 loss eliminates proliferating, but not quiescent, T cells and MEFs. We identify the ribosome assembly factor PWP1 as a substrate of the CRL4DCAF1 ligase. DCAF1 loss results in PWP1 accumulation, impairing rRNA processing and ribosome biogenesis. Knockdown or overexpression of PWP1 can rescue defects or cause similar defects as DCAF1 loss, respectively, in ribosome biogenesis. DCAF1 loss increases free RPL11, resulting in L11-MDM2 association and p53 activation. Cumulatively, these results reveal a critical function for DCAF1 in ribosome biogenesis and define a molecular basis of DCAF1 function in cell proliferation and development.

[Rupture of Ovarian Metastasis from Cecal Cancer during Chemotherapy - A Case Report Suggestive of Bilateral Salpingo-Oophorectomy].

A 66-year-old woman was diagnosed with advanced cecal cancer with metastases to her right ovary, peritoneum, and liver. Ileocecal resection and right salpingo-oophorectomy were performed as cytoreduction surgery before systemic chemotherapy. The colon cancer metastasized to her left ovary during chemotherapy and grew rapidly until it ruptured spontaneously, although the other metastases sites continued to respond to treatment. Emergent left salpingo-oophorectomy was performed. Pathological findings confirmed ovarian metastasis from colon cancer. Ovarian metastases are less responsive to systemic chemotherapy compared to extra-ovarian metastasis and the rapid growth sometimes occurs as a related symptom. Bilateral salpingo-oophorectomy might be recommended in cytoreduction surgery even if the ovarian metastasis is unilateral.

Laparoscopic excision of a retroperitoneal completely isolated enteric duplication cyst in an adult male: A case report and review of literature.

INTRODUCTION: Duplication cysts are very rare congenital malformations in adults. They are lined by gastrointestinal mucosa, connect to the digestive tract, and share smooth muscular layers and a common blood supply. In rare cases, duplication cysts are completely isolated from the digestive tract and have a proper blood supply. Completely isolated duplication cysts in the retroperitoneum are unusual so it is hard to diagnose them without a surgical resection. PRESENTATION OF CASE: A 19-year-old male presented at our emergency department with sharp abdominal pain. Contrast-enhanced computed tomography detected a 5-cm multilocular cystic mass located in the retroperitoneum, caudal to the pancreatic body. The cystic mass was safely resected with laparoscopic surgery without any complication. The final pathological diagnosis was an epithelium-lined duplication cyst in the retroperitoneal space. There was no evidence of malignancy in the duplication cyst. Intracystic bleeding was assumed to be the cause of the abdominal pain. DISCUSSION: The most common differential diagnoses of retroperitoneal cystic masses are pseudocysts related to pancreatitis, cysts from surrounding structures, and neoplasms. In this case, the cystic mass was diagnosed as completely isolated duplication cyst after surgical resection. It is very rarely observed in adults, but it should be listed on differential diagnoses because it has some possibility of malignancy. CONCLUSION: A completely isolated duplication cyst is very rare but noteworthy because there is some possibility of malignancy, ulcerative bleeding, and perforation. A surgical resection is recommended for diagnostic treatment. Laparoscopic surgery is favorable for intraoperative inspection and it is minimally invasive.

Establishment of practical recellularized liver graft for blood perfusion using primary rat hepatocytes and liver sinusoidal endothelial cells.

Tissue decellularization produces a three-dimensional scaffold that can be used to fabricate functional liver grafts following recellularization. Inappropriate cell distribution and clotting during blood perfusion hinder the practical use of recellularized livers. Here we aimed to establish a seeding method for the optimal distribution of parenchymal and endothelial cells, and to evaluate the effect of liver sinusoidal endothelial cells (LSECs) in the decellularized liver. Primary rat hepatocytes and LSECs were seeded into decellularized whole-liver scaffolds via the biliary duct and portal vein, respectively. Biliary duct seeding provided appropriate hepatocyte distribution into the parenchymal space, and portal vein-seeded LSECs simultaneously lined the portal lumen, thereby maintaining function and morphology. Hepatocytes co-seeded with LSECs retained their function compared with those seeded alone. Platelet deposition was significantly decreased and hepatocyte viability was maintained in the co-seeded group after extracorporeal blood perfusion. In conclusion, our seeding method provided optimal cell distribution into the parenchyma and vasculature according to the three-dimensional structure of the decellularized liver. LSECs maintained hepatic function, and supported hepatocyte viability under blood perfusion in the engineered liver graft owing to their antithrombogenicity. This recellularization procedure could help produce practical liver grafts with blood perfusion.

Identification of keratin 19-positive cancer stem cells associating human hepatocellular carcinoma using CYFRA 21-1.

The current lack of an easily measurable surrogate marker of cancer stem cells (CSCs) prevents the clinical application of CSCs for hepatocellular carcinoma (HCC). We previously reported that keratin 19 (K19) is a novel HCC-CSC marker associated with transforming growth factor beta (TGFß)/Smad signaling, and that K19+ HCC-CSCs could be a new therapeutic target of TGFß receptor 1 inhibitor LY2157299. In this study, we examined whether K19+ HCC-CSCs can be tracked using cytokeratin 19 fragment CYFRA 21-1. In 147 HCC patients who underwent curative resection and evaluated K19 expression by immunohistochemistry, preoperative serum CYFRA 21-1 levels were significantly higher in K19+ patients than in K19- patients (P < 0.01). Receiver operating characteristic analyses revealed that serum CYFRA 21-1 was the statistically significant and the most sensitive predictor of tumor K19 expression among preoperative laboratory test values (P < 0.001). In HCC cells encoding with a K19 promoter-driven enhanced green fluorescent protein, fluorescence-activated cell sorting (FACS)-isolated K19+ cells displayed significantly higher levels of supernatant CYFRA 21-1 than K19- cells (P < 0.01). Gain/loss of K19 function experiments confirmed that CYFRA 21-1 levels were regulated by K19 function in HCC cells. Furthermore, CYFRA 21-1 levels reflected the treatment efficacy of LY2157299 in K19+ cells. In conclusion, CYFRA 21-1 can be used to predict K19 expression in HCC, and should thereby aid in the development of novel therapeutic strategies targeting K19+ HCC-CSCs.

A novel three-dimensional culture system maintaining the physiological extracellular matrix of fibrotic model livers accelerates progression of hepatocellular carcinoma cells.

Liver fibrosis is characterized by the progressive accumulation of extracellular matrix (ECM) and is a strong predictor of hepatocellular carcinoma (HCC) development and progression. However, the effect of ECM in fibrotic livers on HCC cells is poorly understood. The aims of this study were to create a new culture system that retained the natural ECM of fibrotic model livers and to establish whether natural ECM regulated the characteristics of HCC cells. Using an organ decellularization technique, we created a new culture system that preserved the tissue-specific ECM of fibrotic model livers from CCl4-treated rats. The content of ECM in fibrotic model liver scaffolds was increased and the ECM microstructure was distorted. Quantitative polymerase chain reaction and immunofluorescence assays of HCC cells cultured in fibrotic model liver scaffolds for 7 days showed an epithelial-mesenchymal transition phenotype. Moreover, the ECM of fibrotic model livers promoted proliferation and chemoresistance of HCC cells. These results showed a novel effect of natural ECM in fibrotic model livers on the malignant behaviour of HCC cells. This new culture system will be useful for both understanding the cell biology of fibrotic livers and developing novel anti-cancer drugs.

Generation of non-viral, transgene-free hepatocyte like cells with piggyBac transposon.

Somatic cells can be reprogrammed to induced hepatocyte-like cells (iHeps) by overexpressing certain defined factors in direct reprogramming techniques. Of the various methods to deliver genes into cells, typically used genome-integrating viral vectors are associated with integration-related adverse events such as mutagenesis, whereas non-integrating viral vectors have low efficiency, making viral vectors unsuitable for clinical application. Therefore, we focused on developing a transposon system to establish a non-viral reprogramming method. Transposons are unique DNA elements that can be integrated into and removed from chromosomes. PiggyBac, a type of transposon, has high transduction efficiency and cargo capacity, and the integrated transgene can be precisely excised in the presence of transposase. This feature enables the piggyBac vector to achieve efficient transgene expression and a transgene-free state, thus making it a promising method for cell reprogramming. Here, we attempted to utilize the piggyBac transposon system to generate iHeps by integrating a transgene consisting of Hnf4a and Foxa3, and successfully obtained functional iHeps. We then demonstrated removal of the transgene to obtain transgene-free iHeps, which still maintained hepatocyte functions. This non-viral, transgene-free reprogramming method using the piggyBac vector may facilitate clinical applications of iHeps in upcoming cell therapy.

Mitogenic and oncogenic stimulation of K433 acetylation promotes PKM2 protein kinase activity and nuclear localization.

Alternative splicing of the PKM2 gene produces two isoforms, M1 and M2, which are preferentially expressed in adult and embryonic tissues, respectively. The M2 isoform is reexpressed in human cancer and has nonmetabolic functions in the nucleus as a protein kinase. Here, we report that PKM2 is acetylated by p300 acetyltransferase at K433, which is unique to PKM2 and directly contacts its allosteric activator, fructose 1,6-bisphosphate (FBP). Acetylation prevents PKM2 activation by interfering with FBP binding and promotes the nuclear accumulation and protein kinase activity of PKM2. Acetylation-mimetic PKM2(K433) mutant promotes cell proliferation and tumorigenesis. K433 acetylation is decreased by serum starvation and cell-cell contact, increased by cell cycle stimulation, epidermal growth factor (EGF), and oncoprotein E7, and enriched in breast cancers. Hence, K433 acetylation links cell proliferation and transformation to the switch of PKM2 from a cytoplasmic metabolite kinase to a nuclear protein kinase.

Comparative study of transplantation of hepatocytes at various differentiation stages into mice with lethal liver damage.

Hepatocyte transplantation utilizing induced pluripotent stem cells (iPSCs) or embryonic stem cells (ESCs) has been expected to provide an alternative to liver transplantation. However, it remains uncertain precisely which cell type is the best suited for cell transplantation. In particular, it is unclear whether mature hepatocytes, which have sufficient liver function, or immature hepatic progenitor cells, which have a higher proliferative capacity, will provide a better outcome. The main objective of this study was to investigate the therapeutic efficacy of the transplantation of hepatocytes at various differentiation stages. We utilized transgenic mice that expressed diphtheria toxin (DT) receptors under the control of an albumin enhancer/promoter. ESC-derived endodermal cells, fetal hepatocytes, and adult hepatocytes were transplanted into these mice with experimentally induced lethal acute liver injury caused by DT administration. The transplanted cells were marked by enhanced green fluorescent protein. We evaluated their effects on survival. At 35 days after transplantation, the survival rate of the adult hepatocyte-transplanted group (8/20, 40%) was significantly improved in comparison to that of the sham-operated group (2/25, 8%), the fetal hepatocyte-transplanted group (1/20, 5%), and the ESC-derived endodermal cell-transplanted group (0/21, 0%). The adult hepatocytes proliferated in the recipient livers and replaced a large part of their parenchyma. The transplantation of adult hepatocytes for acute liver failure significantly improved the survival rate in comparison to that of transplantation of immature cells, thus suggesting that ESCs and iPSCs should be differentiated into mature hepatocytes before cell transplantation for acute liver failure.

Blunted heart rate circadian rhythms in small for gestational age infants during the early neonatal period.

Infants born with intrauterine growth restriction are at increased risk for adverse cardiovascular outcomes in neonatal and later life. Although circadian rhythm is a prognostic marker of cardiovascular health, the concern over the circadian rhythm of these infants is rarely observed. To determine the influence of intrauterine growth retardation on the pattern of circadian rhythm, heart rate (HR) circadian rhythmicity was analyzed in 39 small for gestational age (SGA; birth weight and height below <-2.0 standard deviation score [SDS]) and 117 appropriate for gestational age (AGA; >-1.5 to <1.5 SDS) infants within 72 hours of birth using spectral analysis and cosinor analysis. Amplitude, midline estimating statistic of rhythm, and acrophase calculated from circadian rhythm were analyzed with clinical variables. A significant HR circadian rhythm was observed in 23.1% of the SGA and 24.8% of the AGA group without significant differences; however, SGA infants exhibited remarkable smaller amplitudes compared with AGA in all gestational age (GA) groups (p < 0.001). Amplitudes in AGA infants were positively correlated with the GA or body composition relevant variables (p < 0.001, respectively), but not SGA infants. The blunted HR circadian rhythmicity in SGA infants showed in this study might indicate the vulnerability to pathophysiological condition and could potentially refer to cardiovascular disease in later life.

Splenectomy does not offer immunological benefits in ABO-incompatible liver transplantation with a preoperative rituximab.

BACKGROUND: Preformed anti-ABO antibodies are primarily responsible for antibody-mediated rejection (AMR) after ABO-incompatible (ABO-I) liver transplantation (LT) resulting in lethal hepatic necrosis and biliary complications. Splenectomy, an integral part of protocol for ABO-I LT, decreases anti-ABO antibodies. With the preoperative rituximab prophylaxis, role of the splenectomy for ABO-I LT is now under debate. We investigated the necessity of splenectomy by retrospective analyses of the short-term anti-ABO antibody response and long-term outcomes of ABO-I LT. METHODS: Thirty-seven ABO-I LTs performed from May 2006 through July 2009, at Kyoto University Hospital, Kyoto, Japan, were retrospectively analyzed. Twenty-seven patients who underwent splenectomy (splenectomy group) received 329.6 ± 35.8 mg rituximab 17.7 ± 11.9 days before living donor LT. Ten patients without splenectomy (nonsplenectomy group) received 320.0 ± 10.3 mg rituximab 26.6 ± 21.3 days before transplantation. All patients received a posttransplant hepatic artery infusion with prostaglandin E1 and methylprednisolone. Perioperative anti-ABO immunoglobulin M and immunoglobulin G antibody titers, rejections, biliary complications, infections, and survival results were compared. RESULTS: Preoperative rituximab with plasma exchange effectively reduced anti-ABO antibodies in both patient groups at the time of LT. There was no statistically significant difference observed in anti-ABO immunoglobulin M and immunoglobulin G antibody titers between the "splenectomy" and "nonsplenectomy" groups during the initial 8 weeks. The clinical outcomes, including AMR, biliary complications, infections, and survival, were similar in both the groups. CONCLUSIONS: Preoperative rituximab effectively decreased the anti-ABO antibodies sufficiently to prevent the AMR irrespective of splenectomy. Splenectomy does not offer any immunological benefit in ABO-I LT with preoperative rituximab.

Alpha-fetoprotein-producing pancreatic cancer cells possess cancer stem cell characteristics.

We aimed to demonstrate the existence of cancer stem cells in human pancreatic cancer, and to clarify that they are alpha-fetoprotein (AFP) producing cells. Six cell lines derived from human pancreatic cancers were examined, and AsPC-1 and PANC-1 were noted to express AFP. Single cell culture assays and xenotransplantation revealed that the AFP-producing cells had the capacity for self-renewal and differentiation, and that these cells were tumorigenic. Furthermore, they were resistant to anti-cancer agents. The ABCA12 transporter was expressed in the AFP-producing cells at a level more than twice as high as that in the non-AFP-producing cells. The AFP-producing cells were shown to be putative pancreatic cancer stem cells. Furthermore, the expression of ABCA12 appears to be associated with drug resistance.

Effect of brown seaweed lipids on fatty acid composition and lipid hydroperoxide levels of mouse liver.

Brown seaweed lipids from Undaria pinnatifida (Wakame), Sargassum horneri (Akamoku), and Cystoseira hakodatensis (Uganomoku) contained several bioactive compounds, namely, fucoxanthin, polyphenols, and omega-3 polyunsaturated fatty acids (PUFA). Fucoxanthin and polyphenol contents of Akamoku and Uganomoku lipids were higher than those of Wakame lipids, while Wakame lipids showed higher total omega-3 PUFA content than Akamoku and Uganomoku lipids. The levels of docosahexaenoic acid (DHA) and arachidonic acid (AA) in liver lipids of KK-A(y) mouse significantly increased by Akamoku and Uganomoku lipid feeding as compared with the control, but not by Wakame lipid feeding. Fucoxanthin has been reported to accelerate the bioconversion of omega-3 PUFA and omega-6 PUFA to DHA and AA, respectively. The higher hepatic DHA and AA level of mice fed Akamoku and Uganomoku lipids would be attributed to the higher content of fucoxanthin of Akamoku and Uganomoku lipids. The lipid hydroperoxide levels of the liver of mice fed brown seaweed lipids were significantly lower than those of control mice, even though total PUFA content was higher in the liver of mice fed brown seaweed lipids. This would be, at least in part, due to the antioxidant activity of fucoxanthin metabolites in the liver.