[Show abstract][Hide abstract]ABSTRACT: Background:
Surgical interventions for symptomatic gallstone disease could be dangerous in patients with severe comorbid conditions including liver cirrhosis. Here, we report our experience of living donor liver transplantation (LDLT) indicated for two patients with liver cirrhosis complicated with gallstone diseases.
A 70-year-old woman with a history of hepatitis C virus infection was diagnosed as symptomatic choledocholithiasis. She had open cholecystectomy and choledochotomy with choledocholithotomy, which complicated with postoperative liver failure. Her Child-Pugh score increased from 7 to 12 points and Model for End-Stage Liver Disease (MELD) score from 11 to 36. She underwent LDLT, using the right lobe graft donated by her 47-year-old daughter. The post-transplant graft function was excellent, and the patient was discharged from the hospital on postoperative day 27.
A 46-year-old man with a history of hepatitis B virus infection was diagnosed as cholecystitis. He had cholecystostomy without any complications and his Child-Pugh score remained to be 9 and MELD score 17, followed by LDLT using the right lobe graft donated by his 45-year-old wife. The post-transplant graft function was excellent, and the patient was discharged from the hospital on postoperative day 44.
LDLT is one of treatment options when patients with Child-Pugh B cirrhosis accompanied with gallstone diseases, likely to be deteriorating their liver functions in the near future.
[Show abstract][Hide abstract]ABSTRACT: We present a successful case of thoracic endovascular aortic repair (TEVAR) for chronic Stanford type B aortic dissection (B-AD) with recurrent ischemic colitis. The patient was a 56-year-old woman with abdominal pain as the main complaint who had two operations previously: the total arch replacement 8 years ago and the Bentall 7 years ago for acute Stanford type A aortic dissection. Her abdominal pain worsened as her blood pressure became low during her hemodialysis treatment. An enhanced computed tomography scan was performed on the patient and showed chronic B-AD that occurred from the distal anastomotic part of the total arch graft to the bilateral common iliac arteries. The celiac artery and superior mesenteric artery (SMA) arose from the true lumen, and these were compressed by the expanded false lumen. Her complicated chronic B-AD was treated with the Zenith Dissection Endovascular System, and its procedure was performed as her proximal entry tear was covered by a proximal tapered Zenith TX2 stent graft, supplemented by a noncovered aortic stent extending across both renal arteries, the SMA, and the celiac artery. Seven days after this operation, enhanced computed tomography showed that the patient's true lumen was expanded and her blood flow to the true lumen and SMA was improved. On the other hand, her false lumen tended to be thrombosed. Consequently, she was discharged 10 days after the operation without any postoperative complications as she had no abdominal complaints even though she underwent hemodialysis three times per week after the operation. We believe that TEVAR supplemented by a noncovered aortic stent is an effective treatment, even for highly chronic B-AD in dialysis patients.
[Show abstract][Hide abstract]ABSTRACT: Although it occurs worldwide, hepatitis E virus (HEV) infection in developed countries is generally foodborne. HEV infection is subclinical in most individuals. Although fulminant liver failure may occur, progression to chronic hepatitis is rare. This study describes a 41-year-old man with liver cirrhosis caused by non-alcoholic steatohepatitis and hepatocellular carcinoma within the Milan criteria. His liver function was classified as Child-Pugh grade C. Living donor liver transplantation (LDLT) was performed, and he was discharged from the hospital on postoperative day (POD) 22. However, his alanine aminotransferase concentration began to increase on POD 60 and HEV infection was detected on POD 81. Retrospective assessments of stored blood samples showed that this patient became positive for HEV RNA on POD 3. The liver donor was negative for anti-HEV antibodies and HEV RNA. However, the platelet concentrate transfused into the liver recipient the day after LDLT was positive for HEV RNA. The patient remained positive for HEV infection for 10 months. Treatment with 800 mg/day ribavirin for 20 weeks reduced HEV RNA to an undetectable level. In conclusion, this report describes a patient infected with HEV through a blood transfusion after LDLT, who progressed to chronic hepatitis probably due to his immunosuppressed state and was treated well with ribavirin therapy.
[Show abstract][Hide abstract]ABSTRACT: A 62-year-old woman was admitted for acute epigastralgia and high-grade fever of over 39 °C. The patient had undergone splenectomy for idiopathic portal hypertension 1 year ago and vaccination against Streptococcus pneumoniae immediately post operation. She developed localized peritoneal irritation and abdominal distension. Her serum creatinine had increased to 1.5 mg/dL and procalcitonin was 12.5 ng/ml. Computed tomography of the abdomen revealed edematous large intestine and increased ascites. From these results, the patient was considered to have spontaneous bacterial peritonitis (SBP). Vancomycin (VCM) and doripenem (DRPM) were administered to control the infection. Unexpectedly, S. pneumoniae was detected in the blood culture. Hence, ampicillin/sulbactam was administered after discontinuing VCM. The patient recovered without any life-threatening complications and was discharged after 10 days. In conclusion, overwhelming postsplenectomy infection (OPSI) due to S. pneumoniae could develop in patient with splenectomy even after vaccination. Although the bacteremia probably due to SBP and acute renal dysfunction was accompanied by OPSI, our patient recovered rapidly.
[Show abstract][Hide abstract]ABSTRACT: A 67-year-old man was diagnosed with rectal cancer. The tumor invaded the subserosal layer, but it was not large, and there was no sign of obstruction. Neo-adjuvant chemotherapy reduced the size of the tumor. The patient was admitted to our hospital for surgery. For mechanical bowel preparation, he ingested 34 g of magnesium citrate (Magcorol P®), but then developed severe shock, a disturbance of consciousness, and acidemia, and he required catecholamines and mechanical ventilation. X-ray, CT, and laboratory tests revealed ischemic colitis, toxic megacolon, and hypermagnesemia (16.3 mg/dL). After 2 days of temporary hemodialysis and an enema to reduce his blood magnesium concentration, he recovered and left the intensive care unit. However, the left side of his colon had suffered ischemic damage and become irreversibly atrophied. One month later, he underwent laparoscopic abdominoperineal resection and left-side colectomy for the rectal cancer and severe ischemic colitis of the left side of the colon. Histopathology confirmed the rectal cancer with a grade 2 chemotherapeutic effect and severe ischemic colitis of the left side of the colon. Hence, the present case suggests that severe ischemic colitis, toxic megacolon, and hypermagnesemia can occur after taking a magnesium laxative without obstruction of the intestine.
[Show abstract][Hide abstract]ABSTRACT: Purposes:
The aim of this study was to evaluate the risk factors for the two-year survival after revascularization of critical limb ischemia.
Between 2008 and 2012, 142 patients underwent revascularization. A retrospective analysis was performed to measure the risk factor.
A total 85 patients underwent surgical revascularization, 31 patients underwent endovascular therapy while 26 patients underwent hybrid therapy. By multivariate analysis, the following variables were considered to be risk factors: ejection fraction <50 % (HR, 3.14; 95% CI, 1.22-7.95; P = 0.02), serum albumin level <2.5 g/dL (HR, 3.45; 95% CI, 1.01-11.7; P = 0.04) and nonambulatory status (HR, 4.11; 95% CI, 1.79-9.70; P < 0.01). The two-year survival rate of the patients with no risk factors was 85.5%, while the patients with at least one risk factor had an unfavorable prognosis (one; 56.7%, two; 45.4%).
The nonambulatory status, serum albumin level <2.5 g/dL and ejection fraction <50% were the risk factors for the two-year mortality after revascularization in critical limb ischemia patients. These risk factors may be useful for the treatment strategy of critical limb ischemia patients.
[Show abstract][Hide abstract]ABSTRACT: Trifluridine (FTD) is a key component of the novel oral antitumor drug TAS-102 (also named TFTD), which consists of FTD and a thymidine phosphorylase inhibitor. FTD is supposed to exert its cytotoxicity via massive misincorporation into DNA, but the underlying mechanism of FTD incorporation into DNA and its correlation with cytotoxicity are not fully understood. The present study shows that several antibodies against 5-bromo-2′-deoxyuridine (BrdU) specifically cross-react with FTD, either anchored to bovine serum albumin or incorporated into DNA. These antibodies are useful for several biological applications, such as fluorescence-activated cell sorting, fluorescent immunostaining and immunogold detection for electron microscopy. These techniques confirmed that FTD is mainly incorporated in the nucleus during S phase in a concentration-dependent manner. In addition, FTD was also detected by immunohistochemical staining in paraffin-embedded HCT-116 xenograft tumors after intraperitoneal administration of FTD. Intriguingly, FTD was hardly detected in surrounding matrices, which consisted of fibroblasts with marginal expression of the nucleoside transporter genes SLC29A1 and SLC29A2. Thus, applications using anti-BrdU antibodies will provide powerful tools to unveil the underlying mechanism of FTD action and to predict or evaluate the efficacy and adverse effects of TAS-102 clinically.
Full-text · Article · May 2016 · Scientific Reports
[Show abstract][Hide abstract]ABSTRACT: The most effective treatment for early-stage non-small cell lung cancer (NSCLC) is surgical resection. Nevertheless, up to 20% of patients, even those with stage I NSCLC, relapse after surgery and die. The prognostic nutritional index (PNI) is used to assess immunonutritional conditions or is a predictor of postoperative recurrence in patients with digestive malignancies. However, the usefulness of the PNI for lung cancer is still unknown. We retrospectively analyzed clinicopathological features of stage I NSCLC patients to identify predictors of recurrence and to investigate effects of preoperative PNI levels.
[Show abstract][Hide abstract]ABSTRACT: Background: There are few reports about recurrence-related microRNAs (miRNAs) after liver transplantation (LT) for hepatocellular carcinoma (HCC). The purpose of this study was to identify novel recurrence-related miRNAs after living donor liver transplantation (LDLT) for HCC. Methods: At the first step, we performed microarray analyses of primary HCC (T), noncancerous liver (N), and recurrence (M, metastasis) in three patients with posttransplant recurrence. Then, we selected miRNAs with consistently-altered expression in both primary HCC and recurrence as potential candidates of recurrence-related miRNAs. Expression of the miRNAs in HCC and noncancerous liver was assessed in 70 HCC patients who underwent LDLT. The target genes regulated by the recurrence-related miRNAs were identified. Results: MiR-18a expression was increased, and miR-199a-5p expression was decreased in both primary HCC and recurrence. Increased miR-18a expression correlated with high levels of tumor markers, large tumor size, and a high recurrence rate. Decreased miR-199a-5p expression correlated with high levels of tumor markers, portal venous invasion, and a high recurrence rate. In HCC cells, miR-18a regulated the expression of tumor necrosis factor alpha induced protein 3 (TNFAIP3), and miR-199a-5p regulated the expression of hypoxia-inducible factor 1 alpha (HIF1A), vascular endothelial growth factor A (VEGFA), insulin-like growth factor 1 receptor (IGF1R), and insulin-like growth factor 2 (IGF2). Conclusion: Increased miR-18a levels and decreased miR-199a-5p levels are relevant to HCC recurrence after LDLT. MiR-18a and miR-199a-5p could be novel therapeutic targets of recurrent HCC after LDLT. This article is protected by copyright. All rights reserved.
No preview · Article · May 2016 · Liver Transplantation
[Show abstract][Hide abstract]ABSTRACT: Aim:
β-catenin signaling is a major oncogenic pathway in hepatocellular carcinoma (HCC). Since β-catenin phosphorylation by glycogen synthase kinase 3β (GSK3β) and casein kinase 1ε (CK1ε) results in its degradation, mutations affecting these phosphorylation sites cause β-catenin stabilization. However, the relevance of missense mutations in non-phosphorylation sites in exon 3 remains unclear. The current study explores significance of such mutations in addition to addressing the clinical and biological implications of β-catenin activation in human HCC.
Gene alteration in exon3 of CTNNB1, gene expression of β-catenin targets such as glutamate synthetase (GS), axin2, lect2 and regucalcin (RGN), and protein expression of β-catenin were examined in 125 human HCC tissues.
Sixteen patients (12.8%) showed conventional missense mutations affecting codons 33, 37, 41, and 45. Fifteen additional patients (12.0%) had other missense mutations in codon 32, 34, and 35. Induction of exon3 mutation caused described β-catenin target gene upregulation in HCC cell line. Interestingly, conventional and non-phosphorylation site mutations were equally associated with upregulation of β-catenin target genes. Nuclear localization of β-catenin was associated with poor overall survival (p = 0.0461). Of these patients with nuclear β-catenin localization, loss of described β-catenin target gene upregulation showed significant poorer overall survival than others (p = 0.0001).
This study suggests that both conventional and other missense mutations in exon 3 of CTNNB1 lead to β-catenin activation in human HCC. Additionally, the mechanism of nuclear β-catenin localization without upregulation of described β-catenin target genes might be of clinical importance depending on distinct mechanism.
[Show abstract][Hide abstract]ABSTRACT: Background: Fibroblast growth factor receptor 2 (FGFR2) genetic alterations lead to tumor cell proliferation in various types of cancer. We hypothesized that FGFR2 amplification is associated with FGFR2 expression, resulting in tumor growth and poorer outcome in esophagogastric junction (EGJ) adenocarcinoma. Patients and methods: A total of 176 consecutive chemo-naive patients with EGJ adenocarcinoma were enrolled from two academic institutions. FGFR2 amplification was examined by real-time PCR (N = 140) and FGFR2 expression with immunohistochemical staining (N = 176), and compared against clinicopathological factors and patient outcomes. The effects of FGFR2 inhibition or overexpression on cell proliferation, cell cycle, and apoptosis assays were investigated in EGJ adenocarcinoma cell lines. Downstream FGFR2, AKT and ERK were also examined. Results: Based on the correlation between FGFR2 levels and FGFR2 overexpression in vitro, FGFR2 amplification was defined as copy number > 3.0. In clinical samples, FGFR2 amplification and FGFR2 IHC expression were 15% and 61%, respectively. Although these two statuses were significantly correlated (P < 0.05), only FGFR2 IHC expression was significantly associated with tumor depth (multivariate P < 0.001) and overall survival of patients (univariate P = 0.007). Supporting these findings, FGFR2 overexpression was associated with tumor cell proliferation, cell cycle progression, and anti-apoptosis. Selective inhibition of FGFR2 sufficiently suppressed tumor cell proliferation through de-phosphorylation of AKT and ERK. Conclusion: FGFR2 amplification was significantly associated with FGFR2 expression. FGFR2 expression (but not FGFR2 amplification) was associated with tumor growth and patient outcomes. Our findings support FGFR2 as a novel therapeutic target for EGJ adenocarcinoma.
[Show abstract][Hide abstract]ABSTRACT: We designed a phase I trial to investigate the safety, immune responses and clinical benefits of a five-peptide cancer vaccine in combination with chemotherapy. Study subjects were patients positive for HLA-A2402 with locally advanced, metastatic, and/or recurrent gastrointestinal, lung or cervical cancer. Eighteen patients including nine cases of colorectal cancer were treated with escalating doses of cyclophosphamide 4days before vaccination. Five HLA-A2402-restricted, tumor-associated antigen (TAA) epitope peptides from KOC1, TTK, URLC10, DEPDC1 and MPHOSPH1 were injected weekly for 4weeks. Treatment was well tolerated without any adverse events above grade 3. Analysis of peripheral blood lymphocytes showed that the number of regulatory T cells dropped from baseline after administration of cyclophosphamide and confirmed that TAA-specific T cell responses were associated significantly with longer overall survival. This phase I clinical trial demonstrated safety and promising immune responses that correlated with vaccine-induced T-cell responses. Therefore, this approach warrants further clinical studies.
No preview · Article · Apr 2016 · Clinical Immunology
[Show abstract][Hide abstract]ABSTRACT: Background:
This study aimed to determine the effect of fibrin glue and polyglycolic acid (PGA) felt on prevention of pancreatic fistula (PF) after laparoscopic splenectomy in patients with hypersplenism due to liver cirrhosis.
Fifty consecutive patients were enrolled in this prospective study. Twenty-three patients underwent laparoscopic splenectomy with a fibrin sheet (fibrin sheet group). The sealing ability of each treatment was evaluated by an ex vivo pressure test model. Based on the results from ex vivo experiments, 27 patients received prophylaxis using fibrin glue and PGA felt (PGA with fibrin group). The primary endpoint was the incidence of PF.
Significantly more (5, 22%) patients developed PF in the fibrin sheet group than in the PGA with fibrin group (0%, P = .037).
Our new application of fibrin glue and PGA felt is an effective prophylactic procedure for preventing development of PF after laparoscopic splenectomy.
No preview · Article · Apr 2016 · American journal of surgery
[Show abstract][Hide abstract]ABSTRACT: Background:
The use of ABO incompatible (ABOi) graft in living donor liver transplantation (LDLT) has not been an established procedure worldwide.
Four hundred and eight adult LDLTs, using ABOi (n=19) and non-ABOi (n=389) grafts, were performed as a single center experience.
In ABOi-LDLT group (n=19), median isoagglutinin titer before plasma exchange (PE) at LDLT and after LDLT (max) was ×256, ×32 and ×32, respectively. Rituximab was given at 21.8±6.1 days before LDLT and PE was performed 3.7±1.6 times. Although ABOi-LDLTs had increased rate of splenectomy (89.4% vs. 44.7%, P<0.001) and lower portal venous pressure (PVP) at the end of surgery (13.8±1.1 vs. 16.9±0.2 mmHg, P=0.003), other operative factors including graft ischemic time, operative time and blood loss were not different between the groups. Although ABOi-LDLTs had increased incidence of cytomegalovirus infection (52.6% vs. 22.9%, P=0.007), other post-transplant complications including bacterial sepsis and acute rejection were not different between the groups. The 5-year graft survival rate was 87.9% in ABOi-LDLTs and 80.3% in non-ABOi-LDLTs (P=0.373).
ABOi-LDLT could be safely performed, especially under rituximab-based protocol.
[Show abstract][Hide abstract]ABSTRACT: Fewer than 1 % of gastrointestinal stromal tumors (GISTs) are of the esophagus. This report describes a 63-year-old female diagnosed with mixed spindle/epithelioid cell GIST of the esophagus. She was admitted to our hospital with symptoms of nausea and hematemesis. Preoperative imaging showed a huge submucosal tumor in the lower thoracic and abdominal esophagus. Pathologic examination of an endoscopic biopsy sample suggested squamous cell carcinoma. She underwent subtotal esophagectomy and reconstruction with a gastric tube. Postoperative pathological diagnosis revealed a mixed spindle/epithelioid cell type GIST. The tumor measured 8 × 6 cm, with 30–50 mitotic counts per high power field, immunohistochemical positivity for C-kit (CD117) and CD34 and high risk by modified Fletcher classification. Adjuvant chemotherapy with imatinib mesylate was started 3 months after surgery. Preoperative pathological examination, including staining for CD117 and CD34, of biopsy samples of apparently stromal tumors may be required to rule out rare subtypes of GIST.
[Show abstract][Hide abstract]ABSTRACT: Temporal regulation of microtubule dynamics is essential for proper progression of mitosis and control of microtubule plus-end tracking proteins by phosphorylation is an essential component of this regulation. Here we show that Aurora B and CDK1 phosphorylate microtubule end-binding protein 2 (EB2) at multiple sites within the amino terminus and a cluster of serine/threonine residues in the linker connecting the calponin homology and end-binding homology domains. EB2 phosphorylation, which is strictly associated with mitotic entry and progression, reduces the binding affinity of EB2 for microtubules. Expression of non-phosphorylatable EB2 induces stable kinetochore microtubule dynamics and delays formation of bipolar metaphase plates in a microtubule binding-dependent manner, and leads to aneuploidy even in unperturbed mitosis. We propose that Aurora B and CDK1 temporally regulate the binding affinity of EB2 for microtubules, thereby ensuring kinetochore microtubule dynamics, proper mitotic progression and genome stability.
Full-text · Article · Mar 2016 · Nature Communications
[Show abstract][Hide abstract]ABSTRACT: Background and purpose:
The natural history of human T-cell leukemia virus type 1 (HTLV-1), which causes adult T-cell leukemia (ATL) or HTLV-1 associated myelopathy, after liver transplantation is unclear.
We conducted a nationwide survey to investigate the impact of HTLV-1 status on living donor liver transplantation (LDLT) in Japan. We analyzed the cases of 82 HTLV-1-positive recipients and six HTLV-1-negative-before-LDLT recipients who received a hepatic graft from HTLV-1-positive donors.
ATL developed in five recipients who ultimately died. Of these five, two received grafts from HTLV-1-positive donors and three from HTLV-1-negative donors. The 1-, 3-, and 5-year ATL development rates were 4.5%, 6.5%, and 9.2%, respectively. Fulminant hepatic failure as a pre-transplant diagnosis was identified as an independent risk factor for ATL development (p = 0.001). The 1-, 3-, and 5-year survival rates for HTLV-1-positive recipients who received grafts from HTLV-1-negative donors were 79.9%, 66.1%, and 66.1%, and from HTLV-1-positive donors were 83.3%, 83.3%, and 60.8%, respectively. The 1-year survival rate for HTLV-1-negative recipients who received grafts from HTLV-1-positive donors was 33.3%.
Fulminant hepatic failure is an independent risk factor for ATL development in HTLV-1-positive recipients. Grafts from HTLV-1-positive living donors can be transplanted into selected patients. This article is protected by copyright. All rights reserved.
No preview · Article · Mar 2016 · Journal of Hepato-Biliary-Pancreatic Sciences