Oxidative stress and Liver X Receptor agonist induce hepatocellular carcinoma in Non-alcoholic steatohepatitis model.

BACKGROUND AND AIM: The incidence of non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) is progressively increasing. However, the pathophysiology and etiology of NASH progression to HCC are unknown. We hypothesized that steatosis was the key factor in NASH-related hepatocarcinogenesis and aimed to evaluate the effects of long-term liver X receptor (LXR) agonist stimulation on hepatic steatosis induced by a high-fat diet and oxidative stress. METHODS: We used an LXR agonist (T0901317) and CCl4 to induce hepatic steatosis and oxidative stress, respectively. C57BL/6 mice fed with a high-fat diet were treated with either T0901317 + CCl4 (T09 + CCl4 group) or CCl4 alone (CCl4 group). T0901317 (2.5 mg/kg) and CCl4 (0.1 mL/kg) were intraperitoneally administered twice weekly for 24 weeks. RESULTS: The liver-to-body weight ratio was significantly higher in the T09 + CCl4 group than in the CCl4 group. Mice in the T09 + CCl4 group exhibited abnormal lipid metabolism and NASH-like histopathological features. Additionally, all mice in the T09 + CCl4 group developed liver tumors diagnosed as well-differentiated HCC. The genes identified via microarray analysis were related to NASH and HCC development. CONCLUSIONS: By combining long-term LXR agonist stimulation with oxidative stress and a high-fat diet, we successfully reproduced liver conditions in mice similar to those in humans with NASH and progression to HCC. Our results provide new insight into NASH-related HCC progression and therapy.

A novel hydrogel sheet prevents postoperative pancreatic fistula in a rat model.

AIM: To evaluate the efficacy of a novel hydrogel sheet in preventing postoperative pancreatic fistula (POPF). BACKGROUND: Postoperative pancreatic fistula is a life-threatening complication. As no study has reported the use of hydrogel sheets in preventing POPF, their effectiveness for that purpose remains unclear. METHODS: A novel hydrogel sheet made of polyvinyl alcohol (PVA) was prepared by the freeze-thaw method. The pancreatic ducts and surrounding pancreatic parenchyma of rats were transected to induce a pancreatic fistula. Next, the sheet was attached to the transection site. Ascitic fluid amylase and lipase concentrations were measured. Neoveil® , a nonwoven polyglycolic acid (PGA) felt, is already clinically used as an absorbable reinforcing material at pancreatic transection sites. Neoveil® was used for comparison, as was VIEWGEL® , which is marketed as a wound dressing. RESULTS: The hydrogel sheet remained in place 48 hours postoperatively. The ascitic amylase concentrations in the control, VIEWGEL® -treated, Neoveil® -treated, and hydrogel-treated rats, respectively, were 4992.4 ± 5355.7, 1068.4 ± 269.1, 730.2 ± 425.2, and 303.1 ± 240.1 IU/L; the ascitic lipase concentrations were 2279.8 ± 3395.2, 169.5 ± 100.6, 90.4 ± 71.0, and 86.8 ± 59.8 IU/L. The ascitic amylase and lipase levels were significantly lower in the hydrogel group than in the other groups (P < .05). CONCLUSIONS: This novel hydrogel sheet effectively prevents pancreatic fistulas and has promising clinical application potential.

Evaluation of safety for hepatectomy in a novel mouse model with nonalcoholic-steatohepatitis.

AIM: To investigate whether the liver resection volume in a newly developed nonalcoholic steatohepatitis (NASH) model influences surgical outcome. METHODS: For establishment of a NASH model, mice were fed a high-fat diet for 4 wk, administered CCl4 for the last 2 wk, and administered T0901317 for the last 5 d. We divided these mice into two groups: A 30% partial hepatectomy (PH) of NASH liver group and a 70% PH of NASH liver group. In addition, a 70% PH of normal liver group served as the control. Each group was evaluated for survival rate, regeneration, apoptosis, necrosis and DNA expression after PH. RESULTS: In the 70% PH of NASH group, the survival rate was significantly decreased compared with that in the control and 30% PH of NASH groups (P < 0.01). 10 of 32 mice in the NASH 70% PH group died within 48 h after PH. Serum aspartate aminotransferase (AST) levels and total bilirubin (T-Bil) in the NASH 70% PH group were significantly higher than the levels in the other two groups (AST: P < 0.05, T-Bil: P < 0.01). In both PH of NASH groups, signaling proteins involved in regeneration were expressed at lower levels than those in the control group (P < 0.01). The 70% PH of NASH group also exhibited a lower number of Ki-67-positive cells and higher rates of apoptosis and necrosis than the NASH 30% PH group (P < 0.01). In addition, DNA microarray assays showed differences in gene expression associated with cell cycle arrest and apoptosis. CONCLUSION: The function of the residual liver is impaired in fatty liver compared to normal liver. A larger residual volume is required to maintain liver functions in mice with NASH.

Collision tumor consisting of a colorectal adenocarcinoma and dissemination of a gastric adenocarcinoma.

BACKGROUND: Collision tumors, composed of histologically distinct tumor types, are rare entities, especially in the colorectum, and corresponding evidence-based clinical management or treatment strategies are poorly defined. This is the first report of a collision tumor composed of two histologically distinct adenocarcinomas. CASE PRESENTATION: A 78-year-old male showed severe anemia and a 10% body weight loss over 1 month. Preoperative examination revealed T3N1M0 stage IIIA gastric cancer and T3N0M0 stage IIA rectal cancer. Distal gastrectomy and rectectomy with regional lymph node dissection were performed. Immunohistochemistry revealed two distinct adenocarcinomas with gland duct structures - a colorectal adenocarcinoma and a disseminated gastric adenocarcinoma - that had collided to form an invasive tumor on the serosal surface of the anterior rectum wall. CONCLUSION: This extremely rare case of a collision tumor supports that precise immunohistochemical identification of all tumor components is needed for guiding decisions affecting overall prognosis, adjuvant treatment and survival.

Three-dimensional reconstruction of vascular arrangement including the hepatic artery and left gastric vein during gastric surgery.

BACKGROUND: During gastric surgery, precise recognition of the anatomical variations and relationships among gastric tumors and vessels, including the hepatic artery (HA) and left gastric vein (LGV), is required. We utilized a three-dimensional (3D) reconstructed image as a preoperative simulation for gastric surgery. METHODS: We retrospectively analyzed 84 patients who underwent gastrectomy at Tsukuba Medical Center Hospital. This cohort was sequentially divided into a without-3D group (n = 42) and with-3D group (n = 42), and the perioperative outcomes were compared. The 3D image could be used to classify the HA or LGV arrangement pattern. RESULTS: Regarding the HA arrangement, the right HA of 1 patient (2.3 %) was arising from the superior mesenteric artery, the left HA of 8 patients (19 %) was arising from the left gastric artery, 29 patients (69 %) presented a normal rearrangement, and 4 patients (9.5 %) exhibited other arrangements. The analysis of the LGV arrangement revealed that the LGV in 15 patients (36 %) was located on the dorsal side of the common HA, the LGV in 5 patients (12 %) was located on the ventral side of the common HA, the LGV in 12 patients (29 %) was found on the ventral side of the splenic artery, the LGV in 6 patients (14 %) was located on the dorsal side of the splenic artery, and 4 patients (9.5 %) presented other arrangements. The intraoperative blood loss in the without-3D and with-3D groups was 276 ± 430 and 157 ± 170 g, respectively (p = 0.027). CONCLUSIONS: The 3D reconstruction technique was useful for understanding and sharing anatomic information during gastric surgery.

Three-dimensional reconstruction of the vascular arrangement including the inferior mesenteric artery and left colic artery in laparoscope-assisted colorectal surgery.

BACKGROUND: We performed three-dimensional (3D) reconstruction to investigate the vascular anatomy, including the inferior mesenteric artery (IMA), left colic artery (LCA), and inferior mesenteric vein (IMV), for laparoscope-assisted left-side colorectal surgery. Furthermore, we also examined the distances from the root of the IMA to the bifurcation of the LCA and to the IMV using 3D imaging. METHODS: We retrospectively analyzed 46 patients who underwent laparoscope-assisted left-side colorectal surgery via 3D surgical reconstruction at Tsukuba Medical Center Hospital. The branching patterns among the IMA, LCA, and sigmoidal colic artery (SCA) in colon cancer could be classified into three groups (types A, B, and C): type A, in which both arteries (LCA and SCA) branch off from the same point of the IMA; type B, in which the common trunk of the LCA and SCA branches off from the IMA; and type C, in which the LCA and SCA branch off separately from the IMA. The shortest length from the root of the IMA to bifurcation of the LCA and SCA branches (D mm) or to the IMV (d mm) was measured by 3D imaging. RESULTS: The mean D mm and d mm for all cases were 39.4 ± 11.2 and 27.9 ± 9.21 mm, respectively. The D mm from the IMA root to the LCA or SCA branch in types A, B, and C was 37.8 ± 9.21, 40.5 ± 12.7, and 38.6 ± 10.2 mm, respectively. Similarly, the d mm from the IMA root to the IMV in types A, B, and C was 30.2 ± 11.3, 29.9 ± 7.27, and 25.2 ± 10.3 mm, respectively. CONCLUSION: The present 3D reconstruction technique was useful for determining the 3D vascular anatomical pattern including the relative positions of the IMA, SCA, and IMV during laparoscope-assisted left-side colorectal surgery.

[A Case of Advanced Gastric Cancer with a Complete Response to S-1 Neoadjuvant Chemotherapy in an Elderly Patient].

We report a case of advanced gastric cancer that responded completely to S-1 neoadjuvant chemotherapy. An 80-year-old female complained of nausea. A gastroscopy and CT scan revealed advanced gastric cancer with lymph node metastasis (cT4b [diaphragm], cN3a, cM0, cStage III C). S-1 (100 mg/body/day) was administered orally for 14 consecutive days followed by a 7-day interval. After 2 courses of monotherapy, we conducted a total gastrectomy with D2 lymph node dissection. Histological findings revealed that there were no cancer cells in either the primary tumor or the lymph nodes. This meant that the resected lesions were pathologic Grade 3. Our report suggests that S-1 may have a potent therapeutic effect as a neoadjuvant chemotherapy for advanced gastric cancer especially in older patients.