[Show abstract][Hide abstract] ABSTRACT: TNF and Fas/FasL are vital components, not only in hepatocyte injury, but are also required for hepatocyte regeneration. Liver F4/80+Kupffer cells are classified into two subsets; resident radio-resistant CD68+cells with phagocytic and bactericidal activity, and recruited radio-sensitive CD11b+cells with cytokine-producing capacity. The aim of this study was to investigate the role of these Kupffer cells in the liver regeneration after partial hepatectomy (PHx) in mice. The proportion of Kupffer cell subsets in the remnant liver was examined in C57BL/6 mice by flow cytometry after PHx. To examine the role of CD11b+Kupffer cells/Mφ, mice were depleted of these cells before PHx by non-lethal 5 Gy irradiation with or without bone marrow transplantation (BMT) or the injection of a CCR2 (MCP-1 receptor) antagonist, and liver regeneration was evaluated. Although the proportion of CD68+Kupffer cells did not significantly change after PHx, the proportion of CD11b+Kupffer cells/Mφ and their FasL expression was greatly increased at three days after PHx, when the hepatocytes vigorously proliferate. Serum TNF and MCP-1 levels peaked one day after PHx. Irradiation eliminated the CD11b+Kupffer cells/Mφ for approximately two weeks in the liver, while CD68+Kupffer cells, NK cells and NKT cells remained, and hepatocyte regeneration was retarded. However, BMT partially restored CD11b+Kupffer cells/Mφ and recovered the liver regeneration. Furthermore, CCR2 antagonist treatment decreased the CD11b+Kupffer cells/Mφ and significantly inhibited liver regeneration. The CD11b+Kupffer cells/Mφ recruited from bone marrow by the MCP-1 produced by CD68+Kupffer cells play a pivotal role in liver regeneration via the TNF/FasL/Fas pathway after PHx.
PLoS ONE 09/2015; 10(9):e0136774. DOI:10.1371/journal.pone.0136774 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Microscopic involvement of the resection margin could influence the long-term outcome of patients undergoing curative surgery for gastric cancer. Linear staplers, commonly used for gastrectomies, are often equipped with three lines of staples on either side of the resection line. Although multiple lines of staples reinforce closure of the gastric or intestinal stump, they could hinder accurate histopathologic evaluation of the surgical margin of the resected specimen.
We modified a linear stapling device by removing one line (stapler E2) or two lines (stapler E1) of staples on the specimen side, and attempted to dissect a silicon film and then the stomach from a porcine model using the stapling device and examined the distances between the cutting edge and the nearest staple line.
The distance between the cutting edge and the staple line for stapler E1 was significantly greater than the distance between the cutting edge and the nearest staple line for stapler E2 or the control device. Consequently, specimens of exemplary quality were available for pathologic examination of the surgical margin. Moreover, the lack of multiple layers of staples did not result in contamination of the abdominal cavity with gastric juice during laparoscopic procedures in the porcine model.
Stapler E1 is safe and could be useful for the pathologic evaluation of the true surgical margin.
Gastric Cancer 07/2015; DOI:10.1007/s10120-015-0520-1 · 3.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A carcinoma displaying undifferentiated features with dense lymphoplasmacytic infiltration is defined as lymphoepithelioma-like carcinoma (LELC). Intrahepatic cholangiocarcinoma (ICC) with LELC components is rare, and most LELCs are associated with Epstein-Barr virus (EBV). We report here on a case of ICC with LELC components not associated with EBV. A 65-year-old woman was incidentally found to have a hepatic tumor in the caudate lobe. An extended right hepatectomy with lymphadenectomy was performed. Histologically, the tumor was mainly composed of large undifferentiated epithelial cells with vesicular nuclei, prominent nucleoli, indistinct cell borders, and heavy small lymphocytic infiltration, which are the characteristic features of LELC. Immunohistochemical studies revealed that the tumor cells were positive for cytokeratin 19 but were negative for glypican 3. In situ hybridization using EBV-encoded RNA was negative. Therefore, a diagnosis of ICC with LELC components not associated with EBV was made. Because there is limited information available regarding the prognosis and treatment of ICC with LELC components because of the limited number of reported cases, additional studies will be needed to clarify the clinicopathologic features of this disease.
International surgery 04/2015; 100(4):689-95. DOI:10.9738/INTSURG-D-14-00117.1 · 0.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We herein clarified the time course of changes in the serum high mobility group box chromosomal protein-1 (HMGB-1) concentrations in esophageal cancer patients after esophagectomy, and investigated whether the perioperative serum HMGB-1 levels correlate with the administration of neoadjuvant chemoradiation therapy (NACRT) and the postoperative clinical course, especially the occurrence of pulmonary complications, in such patients. Sixty patients who underwent right transthoracic esophagectomy for esophageal cancer were enrolled in this study. The relationship between the perioperative serum HMGB-1 levels and NACRT, and the postoperative severe pulmonary complications were evaluated. Patients with severe pulmonary complications (n = 44) tended to have undergone NACRT more often than those without severe pulmonary complications (n = 16). The preoperative and postoperative day 7 serum HMGB-1 concentrations were significantly higher in patients with severe pulmonary complications than those in patients without severe pulmonary complications. In the univariate and multivariate analyses, the use of NACRT and the preoperative elevations in the serum HMGB-1 levels (>4.2 ng/mL) were found to be significantly associated with pulmonary dysfunction. Furthermore, the response to NACRT was found to be significantly associated with the preoperative serum HMGB-1 levels. The use of NACRT contributes to preoperative serum HMGB-1 elevation, and these were risk factors for the occurrence of severe postoperative pulmonary complications in patients with esophageal cancer after thoracic esophagectomy.
Diseases of the Esophagus 09/2014; DOI:10.1111/dote.12261 · 1.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although the molecular mechanism of desmoplastic reaction (DR) for providing aggressive tumor characteristics is increasingly recognized, the prognostic role of DR has not been investigated in colorectal liver metastasis (CRLM). A pathologic review of 412 patients who underwent hepatectomy for CRLM at 2 independent institutions was conducted. DR in primary tumors was classified as mature, intermediate, or immature on the basis of the existence of keloid-like collagen and myxoid stroma-distinctive histologic products of extracellular matrix remodeling. With respect to DR, 137, 122, and 153 patients were classified as mature, intermediate, and immature, respectively. Immature DRs were associated with higher T and N stages, higher primary tumor grade, synchronous and larger size of liver metastasis, and extrahepatic disease (P≤0.0001 to 0.002). DR significantly influenced the rate of recurrence in extrahepatic sites, including the lung, peritoneum, and local region in the primary tumor (P≤0.0001 to 0.03), rather than the remnant liver. Five-year overall survival rates after hepatectomy were the highest in the mature group (58.9%), followed by intermediate (42.1%) and immature (26.7%) groups. A significant prognostic impact of DR was observed in subset analyses for institutions, primary tumor location, and timing and number of liver metastases. Multivariate analysis revealed that DR was an independent prognostic factor along with T stage of the primary tumor, size of liver metastasis, and extrahepatic disease. Characterizing DR in the primary tumor on the basis of histologic products of cancer-associated fibroblasts is valuable in evaluating prognostic outcome after hepatectomy in CRLM patients.
The American journal of surgical pathology 05/2014; 38(10). DOI:10.1097/PAS.0000000000000232 · 5.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acyl-coenzyme A: cholesterol acyltransferase (ACAT) catalyzes the conversion of free cholesterol (FC) to cholesterol ester, which prevents excess accumulation of FC. We recently found that FC accumulation in hepatic stellate cells (HSCs) plays a role in progression of liver fibrosis, but the effect of ACAT1 on liver fibrosis has not been clarified. In this study, we aimed to define the role of ACAT1 in the pathogenesis of liver fibrosis.
ACAT1-deficient and wild-type mice, or Toll-like receptor 4 (TLR4)(-/-)ACAT1(+/+) and TLR4(-/-)ACAT1(-/-) mice were subjected to bile duct ligation (BDL) for 3 weeks or were given carbon tetrachloride (CCl4) for 4 weeks to induce liver fibrosis.
ACAT1 was the major isozyme in mice and human primary HSCs, and ACAT2 was the major isozyme in mouse primary hepatocytes and Kupffer cells. ACAT1 deficiency significantly exaggerated liver fibrosis in the mouse models of liver fibrosis, without affecting the degree of hepatocellular injury or liver inflammation, including hepatocyte apoptosis or Kupffer cell activation. ACAT1 deficiency significantly increased FC levels in HSCs, augmenting TLR4 protein and downregulating expression of transforming growth factor-β (TGFβ) pseudoreceptor Bambi (bone morphogenetic protein and activin membrane-bound inhibitor), leading to sensitization of HSCs to TGFβ activation. Exacerbation of liver fibrosis by ACAT1 deficiency was dependent on FC accumulation-induced enhancement of TLR4 signaling.
ACAT1 deficiency exaggerates liver fibrosis mainly through enhanced FC accumulation in HSCs. Regulation of ACAT1 activities in HSCs could be a target for treatment of liver fibrosis.
Journal of Hepatology 03/2014; 61(1). DOI:10.1016/j.jhep.2014.03.018 · 11.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Surgical site infection (SSI), the most frequent adverse event after colorectal surgery, leads to longer hospital days and increased healthcare costs. The development of SSI depends on a complex interplay between patient-related and procedure-related factors. This review refers to the several risk factors for the development of SSI and the risk factor index which were indicated by National Nosocomial Infections Surveillance. Furthermore, this review will focus on the prevention of SSI and refer to colon preparation and preventive antibiotics for colorectal surgery.
Nippon rinsho. Japanese journal of clinical medicine 03/2014; 72(1):150-3.
[Show abstract][Hide abstract] ABSTRACT: We herein report a case of IgG4-related autoimmune pancreatitis (AIP). A 72-year-old male with jaundice visited our hospital complaining of epigastralgia. A blood chemistry analysis revealed elevated serum levels of total bilirubin and DUPAN-II. Computed tomography (CT) revealed irregularly shaped pancreatic masses with a stricture of the main pancreatic duct (MPD) in the head and tail that were interposed by marked atrophy with MPD dilation in the body. F-18 fluorodeoxyglucose (FDG)-positron emission tomography/CT revealed abnormally intense FDG uptake only at the masses. During surgery, another small tumor was also found in the atrophied body; therefore, a total pancreatectomy was performed under the diagnosis of multiple pancreatic cancers. The histological analysis revealed fibrosis with dense and diffuse infiltrations of lymphocytes and IgG4-positive plasma cells. The pancreatic parenchyma of the body was firmly replaced by fibrosis. AIP can lead to the formation of multiple pancreatic lesions, and thus the correct diagnosis is occasionally difficult to establish in atypical cases.
Surgery Today 04/2013; 44(6). DOI:10.1007/s00595-013-0553-1 · 1.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
Pulmonary complications after esophagectomy continue to be a significant cause of morbidity and mortality. Although several factors have been implicated to be associated with pulmonary complications after esophagectomy, the prediction of pulmonary complications remains a challenge. The purpose of this study was to evaluate the predictive value of cytokine levels in sera and pleural drainage fluid for pneumonia and hypo-oxygenations following esophagectomy.
A total of 66 patients who underwent esophagectomy for esophageal cancer were retrospectively evaluated for preoperative status, surgical procedures, and postoperative systemic response and laboratory data up to postoperative day (POD) 7. Interleukin-6 (IL-6) and IL-8 levels were also examined in patient sera and pleural drainage fluid until POD 5.
Eighteen patients (27.3%) had pneumonia following esophagectomy. Patients with pneumonia had significantly more frequent intraoperative blood transfusions, more frequent re-intubation, longer hospital stays, and higher hospital mortality than those without pulmonary complications. Patients with pneumonia had significantly higher levels of serum and pleural IL-6 immediately after surgery and on POD 1 than those without pneumonia. Univariate and multivariate analyses revealed higher pleural IL-6 levels were associated with postoperative minimum PaO2/FiO2 ratio.
The elevation of pleural IL-6 levels immediately after surgery and on POD 1 may predict the incidence of pneumonia and the levels of postoperative impaired oxygenation following esophagectomy.
Journal of Surgical Research 11/2012; 182(2). DOI:10.1016/j.jss.2012.11.015 · 1.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Endoscopic submucosal dissection (ESD) utilizes electrical coagulation, which can cause burns, fibrosis and adhesion of the stomach and surrounding tissue; these complications might increase the surgical difficulties for subsequent laparoscopy-assisted gastrectomy (LAG) and the risk of complications. However, scarce data are available on the influence of previous ESD on LAG. The purpose of this study was to evaluate the feasibility and safety of LAG following incomplete ESD in patients with early gastric cancer. Ninety-seven patients who underwent LAG were analyzed retrospectively; 17 patients had undergone ESD previously and the remaining 80 patients had no history of ESD. Clinicopathological data and surgical outcomes were compared between the two groups. No differences were observed in surgical outcomes of LAG after ESD in terms of operation time, intraoperative blood loss, total number of harvested lymph nodes, time until start of flatus, and postoperative hospital stay. These results were not influenced by tumor location and operative procedures. In conclusion, in terms of surgical outcomes, LAG is a safe and feasible procedure for the treatment of early gastric cancer regardless of previous endoscopic treatment. LAG may be the first-choice radical treatment after incomplete ESD for early gastric cancer.
[Show abstract][Hide abstract] ABSTRACT: Background/Aims: The safety of whole stomach-preserving Appleby operation with resection of the left gastric artery (LGA) for pancreatic cancer cannot be assured. Methodology: The anatomy of the celiac axis (CA) with special regard to the position of the origin of the LGA was examined. Using 3D images of the vascular architecture reconstructed from volume data of helical CT, the length of the CA and the position of the origin of the LGA from the CA were measured in 53 patients. Results: Among 53 patients, 47 patients (89%) had classical anatomy of the CA branches. The mean length (±standard deviation) of the CA and the distance from the root of the LGA to the bifurcation of the CA were 25.2mm (±4.9) (range 14.6-36.5) and 10.3mm (±4.5) (range 2.4-21.9), respectively. In 23 (45%) cases, the LGA arose farther than 10mm away from the bifurcation of the CA. Among six patients with anatomical variation of the arteries, two (4%) had the LGA directly arising from the aorta. Conclusions: Conservation of the LGA at modified Appleby operation would give complete cancer removal by en bloc resection of the nerve plexus, without risk of ischemic complications of the stomach and liver.
[Show abstract][Hide abstract] ABSTRACT: Recently, novel intracorporeal esophagojejunostomy using a linear stapler after laparoscopic total gastrectomy (LTG) was reported and termed as the overlap method. In this study, we evaluated the feasibility and safety of the overlap method for esophagojejunostomy or esophagogastrostomy after LTG or laparoscopic proximal gastrectomy (LPG), respectively.
Twenty-five patients underwent anastomosis using a linear stapler during esophagojejunostomy and esophagogastrostomy after LTG and LPG, respectively. Clinicopathological data and surgical outcomes were evaluated.
The average surgical duration for LTG was 236.8 min compared with 224.1 min for LPG. Postoperative complications were observed in four patients (16.0%); these included a wound infection, an intestinal obstruction, an afferent loop syndrome, and a reflux symptom. The average postoperative hospital stay of the patients was 12.5 days. There was no case of conversion to open surgery, anastomotic leakage or stenosis, or mortality.
The overlap method for esophagojejunostomy or esophagogastrostomy after LTG or LPG is safe and feasible and does not require an additional minilaparotomy, which may result in less pain and favorable cosmetic outcomes.
Langenbeck s Archives of Surgery 03/2012; 397(5):833-40. DOI:10.1007/s00423-012-0939-3 · 2.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Caco-2 cells, cultured with mononuclear cells, were used as an in vitro model of human intestinal cell function. This study shows the effect of glutamine (Gln) supplementation on the production of tumor necrosis factor alpha, interleukin-10 (IL-10), and interleukin-6 (IL-6).
Confluent Caco-2 cells were cultured in media with Gln at 0 mmol/L, 4 mmol/L, or 10 mmol/L +/- 1 microg/mL lipopolysaccharide (LPS), treated with fluorescein isothiocyanate- (FITC-) conjugated intercellular adhesion molecule-1 (ICAM-1) mononuclear antibody, and assessed for ICAM-1 expression levels via flow cytometry. Confluent Caco-2 cells alone in apical inserts, or mononuclear cells (MNCs) alone in basal chambers of transwells, were cultured in media with 0 mmol/L, 4 mmol/L, or 10 mmol/L Gln. Supernatants were taken to assess cytokine and endotoxin levels. Confluent Caco-2 cells in apical inserts of transwells were cultured in media containing Gln at 0 mmol/L, 4 mmol/L, or 10 mmol/L, whereas MNCs were cultured in the basal chamber in media containing Gln at 4 mmol/L +/- LPS. Supernatants were collected to determine cytokine levels in each chamber.
With Gln supplementation of the media at 10 mmol/L, enterocytes displayed a decrease in ICAM-1 expression. MNCs showed a decrease in tumor necrosis factor alpha and IL-6 production and an increase in IL-10 production when incubated with Caco-2 cells in media supplemented with Gln at 10 mmol/L.
Although cytokine production by Caco-2 or mononuclear cells incubated alone was not influenced by the Gln concentration of the media, cultured together, Gln levels affected cytokine production by mononuclear cells, which suggests that Caco-2 cells produce mediators in Gln-rich conditions that can influence mononuclear cell cytokine production.
Journal of Parenteral and Enteral Nutrition 09/2003; 27(5):333-9. DOI:10.1177/0148607103027005333 · 3.15 Impact Factor