Altered glycosylation associated with dedifferentiation of hepatocellular carcinoma: a lectin microarray-based study.

BACKGROUND: Altered glycosylation associated with hepatocellular carcinoma (HCC) is well documented. However, few reports have investigated the association between dedifferentiation and glycosylation. Therefore, the aim of this study was to analyze glycosylation associated with dedifferentiation of HCC within the same nodule and to investigate glycosyltransferase related to the glycosylation. METHODS: We analyzed resected HCC specimens (n = 50) using lectin microarray to comprehensively and sensitively analyze glycan profiles, and identify changes to glycosylation between well- and moderately-differentiated components within the same nodule. Moreover, we performed immunohistochemical staining of mannosyl(α-1,3-)-glycoprotein ß-1,2-N-acetylglucosaminyltransferase (MGAT1), which is an essential glycosyltransferase that converts high-mannose glycans to complex- or hybrid-type N-glycans. RESULTS: Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans. Therefore, these structures were represented to a greater extent in moderately-differentiated components than in well-differentiated ones. Immunohistochemical staining revealed significantly increased NPA expression and decreased MGAT1 expression in moderately-differentiated components. Low MGAT1 expression in moderately-differentiated components of tumors was associated with intrahepatic metastasis and had tendency for poor prognosis. CONCLUSION: Dedifferentiation of well-differentiated HCC is associated with an increase in high-mannose glycans. MGAT1 may play a role in the dedifferentiation of HCC.

Effects of Sleeve Gastrectomy on Nonalcoholic Fatty Liver Disease in an Obese Rat Model.

BACKGROUND/AIM: Laparoscopic sleeve gastrectomy (SG) is an increasingly used bariatric surgery, which is reported to be effective for nonalcoholic fatty liver disease (NAFLD). Recently, activation of farnesoid X receptor (FXR), which is a nuclear receptor of bile acid (BA), was reported to contribute to the resolution of NAFLD. However, it is unclear whether SG has an effect on expression of FXR in the liver. We aimed to investigate the expression of FXR and its related factors in the liver after SG and to clarify the relationship between changes in FXR expression and NAFLD in an obese rat model. METHODS: Thirty male Zucker fatty rats were divided into three groups: sham-operated (SO) control, pair-fed (PF) control, and SG. Eight weeks after the surgery, metabolic parameters, plasma levels of total BA and liver enzymes, liver triglyceride (TG) content, and mRNA expression of FXR and its related factors, such as small heterodimer partner (SHP) and peroxisome proliferator-activated receptor α (PPARα), were measured. RESULTS: Metabolic parameters in the SG group were significantly improved compared with the SO group. Liver enzymes and TG were significantly lower in the SG group than in the SO group. Plasma levels of BA were significantly higher in the SG group than in the SO and PF groups. mRNA expression of FXR, SHP, and PPARα in the liver was significantly higher in the SG group than in the SO group. CONCLUSIONS: These results suggest that the effects of SG on NAFLD should be associated with the expression of the FXR pathway in the liver in a Zucker fatty rat model.

Characteristics of advanced gastric cancer with negative or only perigastric lymph node metastasis in elderly patients.

OBJECTIVES: After gastrectomy with extended lymph node (LN) dissection, the damage of celiac plexus seems to cause of disorder of eating habits. To clarify the indication of gastrectomy with limited LN dissection for elderly patients, the pathological characteristics of advanced gastric cancer in elderly patients were examined in this study. METHODS: Forty-seven patients aged ≥80 years with advanced gastric cancer (deeper than pT2) who underwent curative gastrectomy from 1998 to 2015 were enrolled. Patients were classified into two groups by extent of LN metastasis: Group A, with N0 or only perigastric LN metastasis (n = 33); Group B, LN metastasis beyond the perigastric area (n = 14). Pathological factors were then evaluated. RESULTS: No significant differences were observed in age, sex, body mass index, American Society of Anesthesiologists physical status classification, serum level of carcinoembryonic antigen, surgical procedure, extent of LN dissection, and number of dissected LNs. Pathological findings showed no significant differences in tumor location, macroscopic type, histologic type, and lymphovascular invasion. However, significant differences were observed in tumor maximum diameter at the cut-off level of 40 mm (Group A: ≤40 mm, n = 10 and >40 mm, n = 23; Group B: ≤40 mm, n = 0 and >40 mm, n = 14; P = 0.02). CONCLUSION: In the elderly patients, LN metastasis in advanced gastric cancer of ≤40 mm in diameter was limited to be within the perigastric area. Gastrectomy with only perigastric LN dissection may be adopted in these patients.

A case of advanced gastric cancer achieved a pathological complete response by chemotherapy.

BACKGROUND: Although chemotherapy is the first recommended treatment of unresectable gastric cancer, a pathological complete response is a rare event. CASE PRESENTATION: A 58-year-old male was diagnosed as gastric cancer with a bulky tumor, lymphadenopathy, and suspicious peritoneal dissemination. The patient underwent chemotherapy with S-1 and cisplatin. After three courses of chemotherapy, a computed tomography showed dramatic improvements in gastric wall thickening, shrinkage of lymphadenopathy, and disappearance of disseminated peritoneal lesion. The patient underwent potentially curative resection by total gastrectomy with D2 lymph node dissection. Histological examination revealed the absence of malignant cells not only in the resected specimen but also in the harvested lymph nodes. At present, more than 7 years after the initial surgery, the patient is still alive without any recurrence. CONCLUSIONS: We obtained a pathological complete response by chemotherapy with S-1 and cisplatin for advanced gastric cancer. Although a pathological complete response is a rare event, it would be associated with the long-term survival of patients with advanced gastric cancer.

A case of undifferentiated-type mucosal gastric cancer with multiple lymph node metastases fulfilling the curative criteria for endoscopic resection according to routine pathological analysis.

BACKGROUND: Endoscopic resection is accepted as the standard treatment for early mucosal gastric cancer, and its indications have recently been expanded while its long-term outcomes are still unclear. Herein, we present a didactic case of undifferentiated-type mucosal gastric cancer fulfilling the expanded indication and curative criteria for endoscopic submucosal dissection (ESD), having synchronous multiple lymph node metastases. CASE PRESENTATION: A 40-year-old woman was found to have a Helicobacter pylori infection at a standard health check with no abdominal symptoms. She received an upper gastrointestinal endoscopy and found to have an undifferentiated-type mucosal gastric cancer with the size of 15 mm in diameter without ulceration, which fulfilled the expanded indication for ESD. According to patient's preference, we performed laparoscopy-assisted distal gastrectomy with D1+ lymph node dissection, and routine pathological analysis revealed a predominantly signet ring cell carcinoma limited to the mucosa without ulceration or any vessel involvement; on the other hand, 15 lymph node metastases were detected. Then, we added deep sectioning of the whole tumoral area at a thickness of 20 µm and immunohistochemical analyses. As the result, an isolated lymphatic capillary involvement of the extremely superficial submucosa was identified in a single histological section, and pathological diagnosis was corrected to ly1. She received postoperative adjuvant chemotherapy with an S-1 oral agent and had no recurrence under strict surveillance for 1 year postoperatively. CONCLUSIONS: When we perform ESD for undifferentiated-type gastric cancer, deep sectioning of the whole tumoral area into thin slices and immunohistochemical staining using D2-40 should be practically considered.

A gastrointestinal stromal tumor at the esophagogastric junction successfully treated by laparoscopic wedge resection with seromuscular layer dissection: a case report.

Herein, we report a case of a gastrointestinal stromal tumor (GIST) at the esophagogastric junction (EGJ) that was successfully treated by a laparoscopic wedge resection (LWR) after dissection of the seromuscular layer around the tumor to prevent postoperative deformities and stenosis of the EGJ. Subsequently, the abdominal esophagus was wrapped by the gastric fornix according to Dor's method in order to prevent reflux esophagitis after surgery.A 71-year-old female patient was admitted with a diagnosis of a GIST (23 × 20 × 20 mm) at the EGJ. We performed the abovementioned operation.Gastroduodenal endoscopic examination revealed no deformity or stenosis of the EGJ at 6 months after the operation. The patient has not experienced any reflux symptoms. Tumor recurrence was not noted 26 months after the operation.This procedure is useful in preventing the deformity and stenosis of the EGJ as well as postoperative reflux esophagitis.

Impact of the VIO system in hepatic resection for patients with hepatocellular carcinoma.

PURPOSES: This study aimed to evaluate a novel surgical device combination [VIO system containing a bipolar clamp (BiClamp) and the monopolar soft-coagulation (SOFT COAG)] in hepatic resection for patients with hepatocellular carcinoma (HCC). METHODS: This study performed 124 hepatic resections for HCC and divided them into 2 groups: 60 patients (Conventional group) underwent liver parenchymal transection using Cavitron Ultrasonic Surgical Aspirator (CUSA) system and saline-coupled bipolar electrocautery for hemostasis; the BiClamp was used with the CUSA system for liver parenchymal transection and SOFT COAG was used with saline-coupled bipolar electrocautery for hemostasis in 64 patients (VIO group). RESULTS: The median blood loss in the VIO group was 345 mL, which was less than that in the Conventional group (median 548 mL, P = 0.0423). A multivariate logistic regression analysis showed that no use of the VIO system (P = 0.0172) was an independent predictor of intraoperative blood loss, respectively. In patients with liver cirrhosis, the VIO group included a significantly lower proportion of patients with liver cirrhosis that experienced more than 500 mL of intraoperative blood loss in comparison to those in the Conventional group (P = 0.0262). CONCLUSIONS: The VIO system was safe for hepatic resection and its use was associated with a significant decrease in intraoperative blood loss even in cirrhotic patients.