Conversion surgery after lenvatinib treatment for multiple lung metastases from hepatocellular carcinoma.

Although systemic treatment for hepatocellular carcinoma has advanced after the development of tyrosine kinase inhibitors such as sorafenib and lenvatinib, the effectiveness of a single tyrosine kinase inhibitor in survival extension of unresectable hepatocellular carcinoma is limited to a few months. Therefore, novel treatment options are required for unresectable hepatocellular carcinomas, including those with multiple lung metastases. This case report describes a hepatocellular carcinoma patient with a recurrence of multiple lung metastases, which was successfully treated with conversion pneumonectomy after treatment with tyrosine kinase inhibitors.

Orthotopic mouse liver transplantation to study liver biology and allograft tolerance.

Orthotopic liver transplantation in the mouse is a powerful research tool that has led to important mechanistic insights into the regulation of hepatic injury, liver immunopathology, and transplant tolerance. However, it is a technically demanding surgical procedure. Setup of the orthotopic liver transplantation model comprises three main stages: surgery on the donor mouse; back-table preparation of the liver graft; and transplant of the liver into the recipient mouse.

Contribution of alloantigens to hepatic ischemia/reperfusion injury: Roles of natural killer cells and innate immune recognition of nonself.

Hepatic ischemia/reperfusion injury (IRI) remains a major clinical problem and involves the innate immune system's recognition of "nonself." Considering the efficient nonself recognition by natural killer (NK) cells, we hypothesize in this study that hepatic IRI associated with liver transplantation (LT) could be augmented in allogeneic rather than in syngeneic (Syn) grafts due to alloantigen recognition by innate immune cells, especially by NK cells. Using green fluorescent protein (GFP)/Sprague-Dawley rats, we tested our hypothesis in a rat LT model with 18 hours of cold storage in University of Wisconsin solution.

[A case of an elderly patient with recurrent GIST, which was effectively treated with low-dose imatinib mesylate].

The recommended dose of imatinib for recurrent gastrointestinal stromal tumors (GIST) is 400mg/day. However, adverse effects limit the use of the standard dose in elderly patients. We report a case of an elderly patient with recurrent GIST, where long-term control of the disease was achieved with low-dose imatinib therapy.

Laparoscopic distal gastrectomy for pyloric stenosis caused by heterotopic glands in a young female: report of a case.

A 17-year-old female was referred to our hospital with worsening dietary intake and abdominal bloating. She had epigastric fullness, but no abdominal pain. Gastrointestinal endoscopy revealed food residue and pyloric stenosis.

Roles of dendritic cells in murine hepatic warm and liver transplantation-induced cold ischemia/reperfusion injury.

Unlabelled: Dendritic cells (DCs) induce and regulate both innate and adaptive immune responses; however, their in vivo functional importance in hepatic ischemia/reperfusion (IR) injury is perplexing. We hypothesized that liver-resident DC and locally recruited blood-borne DC might have distinctive roles in hepatic IR injury. We tested this hypothesis by using DC-deficient, fms-like tyrosine kinase 3 ligand (Flt3L) knockout (KO) mice in hepatic warm (70% partial clamping for 60 minutes) and cold IR injury (liver transplant [LTx] with 24-hour cold storage).

Interferon regulatory factor-2 is protective against hepatic ischemia-reperfusion injury.

Interferon regulatory factor (IRF)-1 is a nuclear transcription factor that induces inflammatory cytokine mediators and contributes to hepatic ischemia-reperfusion (I/R) injury. No strategies to mitigate IRF1-mediated liver damage exist. IRF2 is a structurally similar endogenous protein that competes with IRF1 for DNA binding sites in IRF-responsive target genes and acts as a competitive inhibitor.

Immunomodulatory effect of nuclear factor-κB inhibition by dehydroxymethylepoxyquinomicin in combination with donor-specific blood transfusion.

Background: Nuclear factor-κB (NF-κB) is a key molecule in alloimmune responses, however, its role in tolerance induction is not clear. We have previously reported that dehydroxymethylepoxyquinomycin (DHMEQ), a novel NF-κB inhibitor, prolongs cardiac allograft survival. In this study, we evaluated the immunomodulatory effects of DHMEQ when combined with a donor-specific blood transfusion (DST), and assessed whether the treatment induces tolerance in a mouse heart transplantation model.

The loss of renal dendritic cells and activation of host adaptive immunity are long-term effects of ischemia/reperfusion injury following syngeneic kidney transplantation.

Ischemia/reperfusion injury associated with kidney transplantation induces profound acute injury, influences early graft function, and affects long-term graft outcomes. To determine whether renal dendritic cells play any role during initial innate ischemia/reperfusion injury and the subsequent development of adaptive immune responses, we studied the behavior and function of renal graft and host infiltrating dendritic cells during early and late phases of renal ischemia/reperfusion injury. Wild type to green fluorescent protein (GFP) transgenic rat kidney transplantation was performed with and without 24-h cold storage.

Carbon monoxide inhibits apoptosis during cold storage and protects kidney grafts donated after cardiac death.

Ischemia/reperfusion (I/R) injury remains as a serious deleterious factor in kidney transplantation (KTx). We hypothesized that carbon monoxide (CO), an endogenous potent cytoprotective molecule, inhibits hypothermia-induced apoptosis of kidney grafts. Using the rat KTx model mimicking the conditions of donation after cardiac death (DCD) as well as nontransplantable human kidney grafts, this study examined effects of CO in preservation solution in improving the quality of marginal kidney grafts.

Hepatic B7 homolog 1 expression is essential for controlling cold ischemia/reperfusion injury after mouse liver transplantation.

Unlabelled: Ischemia/reperfusion (I/R) injury remains a key risk factor significantly affecting morbidity and mortality after liver transplantation (LT). B7 homolog 1 (B7-H1), a recently identified member of the B7 family, is known to play important roles in regulating local immune responses. We hypothesized that B7-H1 plays crucial roles during innate immune responses induced by hepatic I/R injury, and using B7-H1 knockout (KO) liver grafts, we tested this hypothesis in the mouse LT model with 24 hours of cold storage.

Critical role of interferon regulatory factor-1 in murine liver transplant ischemia reperfusion injury.

Interferon regulatory factor-1 (IRF-1) is a transcription factor that regulates gene expression during immunity. We hypothesized that IRF-1 plays a pivotal role in liver transplant (LTx) ischemia/reperfusion (I/R) injury. Mouse orthotopic LTx was conducted after 24 hours cold storage in University of Wisconsin (UW) solution in wildtype (WT) C57BL/6 and IRF-1 knockout (KO) mice.

Liver graft exposure to carbon monoxide during cold storage protects sinusoidal endothelial cells and ameliorates reperfusion injury in rats.

Hepatic ischemia/reperfusion (I/R) injury significantly influences short-term and long-term outcomes after liver transplantation (LTx). The critical step initiating the injury is known to include sinusoidal endothelial cell (SEC) alteration during the cold preservation period. As carbon monoxide (CO) has potent cytoprotective functions on vascular endothelial cells, this study examined if CO treatment of excised liver grafts during cold storage could protect SECs and ameliorate hepatic I/R injury.

Donor graft interferon regulatory factor-1 gene transfer worsens liver transplant ischemia/reperfusion injury.

Background: Liver ischemia and reperfusion (IR) injury is a phenomenon that leads to graft dysfunction after liver transplantation. Understanding the molecular mechanisms behind this process is crucial to developing strategies to prevent short- and long-term graft dysfunction. The purpose of this study was to explore the role of the transcription factor interferon regulatory factor-1 (IRF-1) in a model of orthotopic rat liver transplantation.

Inhibition of Kupffer cell-mediated early proinflammatory response with carbon monoxide in transplant-induced hepatic ischemia/reperfusion injury in rats.

Unlabelled: Proinflammatory responses play critical roles in hepatic ischemia/reperfusion (I/R) injury associating with liver transplantation (LTx), and carbon monoxide (CO) can effectively down-regulate them. Using wild-type (WT) to enhanced green fluorescent protein (EGFP)-transgenic rat LTx with 18-hour cold preservation in University of Wisconsin solution, this study analyzed the relative contribution of donor and host cells during early posttransplantation period and elucidated the mechanism of hepatic protection by CO. CO inhibited hepatic I/R injury and reduced peak alanine aminotransferase levels at 24 hours and hepatic necrosis at 48 hours.

Inspection of safety and accuracy of D2 lymph node dissection in laparoscopy-assisted distal gastrectomy.

Background: There is a consensus on the indication of laparoscopy-assisted distal gastrectomy (LADG) for early gastric cancer that needs D1 + alpha or D1 + beta lymph node dissection. However, many gastrointestinal surgeons consider D2 lymph node dissection in LADG to be difficult, therefore, only a few medical institutions have performed D2 lymph node dissection in LADG. We examined the safety and accuracy of D2 dissection in LADG by comparing with open distal gastrectomy (ODG), as the first step to operate on advanced gastric cancer.

The novel NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin, prevents local and remote organ injury following intestinal ischemia/reperfusion in rats.

Background: Nuclear factor-kappaB regulates the expression of several genes involved in inflammation, the immune response, apoptosis, cell survival, and proliferation. Many of these same genes are activated during ischemia/reperfusion (I/R) injury. Here, we examined the anti-inflammatory efficacy of a newly developed nuclear factor-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), in the intestinal I/R injury model of rats.

Protection of transplant-induced hepatic ischemia/reperfusion injury with carbon monoxide via MEK/ERK1/2 pathway downregulation.

Carbon monoxide (CO), a product of heme degradation by heme oxygenases (HO), has been shown to provide cytoprotection in various tissue injury models. This study examined the efficacy and molecular mechanisms of exogenously delivered inhaled CO in protecting liver grafts from cold ischemia/reperfusion (I/R) injury associated with liver transplantation. Orthotopic syngenic liver transplantation (OLT) was performed in Lewis rats with 18-h cold preservation in University of Wisconsin solution.

A novel fully human anti-CD40 monoclonal antibody, 4D11, for kidney transplantation in cynomolgus monkeys.

Background: CD40-CD154 pathway blockade by anti-CD154 monoclonal antibodies (mAbs) significantly prolongs allograft survival in nonhuman primates. However, thromboembolic complications have prevented clinical application. Thus, blockade of the counter molecule by a novel fully human anti-CD40 mAb, 4D11, is an attractive alternative.

Laparoscopic gastrectomy for early gastric cancer targeting as a less invasive procedure.

Background: Since only a few extensive reports are available on the less invasive nature of laparoscopic gastrectomy, we compared postoperative changes over time in vital signs and hematological parameters between this surgery and laparotomic gastrectomy.

Methods: Of 188 patients who underwent distal gastrectomy for preoperatively diagnosed early gastric cancer between January 2004 and September 2006, 87 underwent laparoscopy-assisted distal gastrectomy (LADG) and 101 underwent laparotomic distal gastrectomy (DG). The invasiveness of the two procedures was evaluated in 164 patients with no postoperative complications (82 cases of LADG and 82 cases of DG by measuing vital signs daily and performing hematological examination on postoperative days (POD) 1, 4, 7, and 10.

Control of allograft rejection by applying a novel nuclear factor-kappaB inhibitor, dehydroxymethylepoxyquinomicin.

Background: Nuclear factor (NF)-kappaB plays a crucial role in lymphocyte activation, proliferation, and survival. We examined the immunosuppressive effect of a newly developed NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ) in allotransplantation.

Methods: Purified C57BL/6 (H-2b) T cells were used for in vitro studies examining activation, proliferation, cytokine production and nuclear NF-kappaB and nuclear factor of activated T cells (NFAT) protein levels.

Nonfamilial juvenile polyposis coli in a child: report of a case.

Juvenile polyposis coli (JPC) is an uncommon condition, manifesting as hamartomatous gastrointestinal polyposis with potential malignancy. This report describes a 15-month-old girl who was diagnosed to have nonfamilial JPC accompanied by macrocephaly, clubbed fingers, and mental retardation. Radiography of the colon by a barium enema and total colonoscopy demonstrated numerous colonic polyps.

Postnatal management for prenatally diagnosed choledochal cysts.

Purpose: The aim of this study was to determine an appropriate postnatal management plan for prenatally diagnosed congenital biliary dilatation (CBD).

Methods: Between 1962 and 2002, 5 (5.9 %) of 85 patients had CBD diagnosed prenatally and were examined clinically.