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.

Clinical significance of upper gastrointestinal endoscopy before laparoscopic bariatric procedures in Japanese patients.

PURPOSES: The choice between performing routine and selective upper gastrointestinal endoscopy (UGE) before bariatric surgery remains controversial. This study aimed to evaluate the clinical significance of UGE before laparoscopic bariatric procedures. METHODS: We enrolled 155 obese Japanese patients who underwent laparoscopic bariatric procedures at our institute and evaluated their endoscopic findings, such as reflux esophagitis (RE), hiatal hernia (HH), Barrett's esophagus, gastritis, duodenitis, gastroduodenal ulcer, gastric cancer, and polyps. RESULTS: Preoperative endoscopy revealed abnormal findings in 102 patients (66%), including gastritis in 57 (37%), HH in 51 (32%), RE in 27 (17%), benign gastric polyps in 16 (10%), duodenitis in 6 (4%), and Barrett's esophagus in 1 (0.6%). Two patients with definite HH were treated with simultaneous crural repair at the time of bariatric surgery. Duodenitis was graded as severe in three of these six patients and treated with a proton pump inhibitor before surgery. Eleven patients received therapy to eradicate Helicobacter pylori (H. pylori), either before or after the surgery. In summary, preoperative endoscopy changed the perioperative management for 16 of the 155 patients (10%). CONCLUSIONS: Routine UGE may be necessary before bariatric procedures in obese Japanese patients.

Additional effects of duodenojejunal bypass on glucose metabolism in a rat model of sleeve gastrectomy.

PURPOSE: Sleeve gastrectomy with duodenojejunal bypass (SG-DJB) is expected to become a popular procedure in East Asia. The aim of this study was to evaluate the effects of duodenojejunal bypass on glucose metabolism in a rat model of sleeve gastrectomy (SG). METHODS: Twenty-four Sprague-Dawley rats were divided into two groups: SG-DJB and SG alone. 6 weeks after surgery, body weight, feed intake, and metabolic parameters were measured, and oral glucose tolerance tests (OGTT) were performed. The mRNA expression of factors related to gluconeogenesis and glucose transport was evaluated using jejunal samples. Protein expression of factors with significantly different mRNA expression levels was evaluated using immunohistochemistry. RESULTS: Body weight and metabolic parameters did not significantly differ between the two groups. During the OGTT, the SG-DJB group showed an early increase in serum insulin followed by an early decrease in blood glucose compared with the SG group. Expression levels of glucose transporter 1 (GLUT1) and sodium-glucose cotransporter 1 (SGLT1) mRNA and protein in the alimentary limb (AL) were greater in the SG-DJB group than in the SG group. CONCLUSIONS: The additional effects of duodenojejunal bypass on glucose metabolism after SG may be related to increased expression of GLUT1 and SGLT1 in the AL.

Prognostic factors of non-ampullary duodenal adenocarcinoma.

BACKGROUND: Non-ampullary duodenal adenocarcinoma, excluding carcinoma in the ampulla of Vater, is a rare disease. Although several prognostic factors have been reported, they remain controversial due to the rarity of non-ampullary duodenal adenocarcinoma. The aims of this study were to investigate prognostic factors in patients with non-ampullary duodenal adenocarcinoma and to assess chemotherapy in patients with recurrence. PATIENTS AND METHODS: Records of 25 patients who underwent surgical treatment for non-ampullary duodenal adenocarcinoma from 2004 to 2016 were retrospectively reviewed. The relationship between the clinicopathological factors and outcomes was investigated. RESULTS: Serum level of CA19-9, gross appearance, tumor size, tumor invasion, lymph node metastases, TNM stage and lymphatic and vascular invasion were significant risk factors of recurrence. Patients with recurrence who received chemotherapy according to regimens used to treat colorectal cancer had a better prognosis than those without chemotherapy (P = 0.016). CONCLUSION: Advanced non-ampullary duodenal adenocarcinoma has a poor prognosis, but chemotherapy possibly improves the prognosis in the patients with recurrent non-ampullary duodenal adenocarcinoma.

Control of inferior vena cava injury during laparoscopic surgery using a double balloon-equipped central venous catheter: proof of concept in a live porcine model.

BACKGROUND: Iatrogenic inferior vena cava (IVC) injury is a rare but potentially life-threatening complication during laparoscopic surgery. This experimental study aimed to assess the hemostatic ability of a new device, double balloon-equipped central venous (DB-CV) catheter, for IVC injury. METHODS: The DB-CV catheter comprises a triple-lumen sphincterotome combined with two dilating balloons having a diameter of 25 mm. The experimental procedures were performed in five pigs. The DB-CV catheter was inserted via the right femoral vein. For the IVC occlusion test, correct placement of the balloons was confirmed by indocyanine green fluorescence imaging, and hemodynamic data were recorded. For the IVC injury test, a 3- to 4-mm circumferential incision was created in IVC, and hemostasis was initiated using balloon inflation 5 s after the injury. RESULTS: Hemodynamic changes were minimal, with a 20 mmHg reduction in the mean arterial pressure because of IVC occlusion. All bleeding from IVC injuries was successfully temporarily stopped by direct balloon compression, with a mean time to hemostasis of 69 s and mean blood loss of 32 ml. Subsequently, the positioning of IVC injuries between two balloons made it possible to suture the injured IVC. CONCLUSIONS: Balloon occlusion using the DB-CV catheter provides a rapid temporal hemostatic effect and can overcome the serious condition of massive hemorrhage from IVC injuries.

Laparoscopic liver resection in cirrhotic patients with specific reference to a difficulty scoring system.

PURPOSE: Laparoscopic liver resection is widely used for liver tumors, but its utility in patients with cirrhosis remains controversial. The aim of this study was to assess the surgical outcomes of laparoscopic liver resection in patients with liver cirrhosis with specific reference to a difficulty scoring system. METHODS: From January 2010 to March 2016, the outcomes of laparoscopic liver resection in 95 patients were retrospectively reviewed. Surgical outcomes were analyzed to identify differences between the liver cirrhosis and non-liver cirrhosis groups; these groups were further stratified to high and low difficulty scores. The surgical outcomes of both groups were compared according to the difficulty scores. RESULTS: Overall, 53/95 (55.8%) patients were diagnosed with liver cirrhosis. There were no significant differences in surgical duration, blood loss, postoperative hospital stay, and morbidity between groups, although liver function was worse in the liver cirrhosis group than in the non-liver cirrhosis group. Multivariate analysis showed that the difficulty score was an independent predictor of increased blood loss. In particular, blood loss in cirrhotic patients was significantly greater with a high difficulty score than with a low difficulty score. CONCLUSIONS: The safety profile of laparoscopic liver resection was the same in patients with and without liver cirrhosis. However, patients with liver cirrhosis and a high difficulty score require extra attention, because of a higher risk for perioperative blood loss.

Long-term outcomes of laparoscopic versus open splenectomy for immune thrombocytopenia.

PURPOSE: Splenectomy is the standard therapy for medically refractory immune thrombocytopenia (ITP). Laparoscopic splenectomy (LS) has gained wide acceptance; however, the long-term outcomes of LS versus open splenectomy (OS) for patients with ITP remain unclear. METHODS: We analyzed, retrospectively, 32 patients who underwent splenectomy, as LS in 22 and OS in 10, for refractory ITP at our institute. Data were evaluated based on the American Society of Hematology 2011 evidence-based practice guidelines for ITP. RESULTS: Although the operation time was significantly longer in the LS group (p < 0.01), LS was associated with less blood loss (p < 0.01), infrequent blood transfusion during surgery (p < 0.01), quicker resumption of oral intake (p < 0.01), and shorter hospital stay (p < 0.01) than OS. Positive responses, including complete and partial remission, were achieved in 90% of the OS group patients and 77% of the LS group patients. The mean follow-up periods were 183 and 92 months, respectively. Relapse-free survival rates, 15 years after the operation were 63% in the OS group and 94% in the LS group. CONCLUSIONS: LS can provide better short-term results and comparable long-term results to those of OS for ITP.

Secondary Unconjugated Bile Acids Induce Hepatic Stellate Cell Activation.

Hepatic stellate cells (HSCs) are key players in liver fibrosis, cellular senescence, and hepatic carcinogenesis. Bile acids (BAs) are involved in the activation of HSCs, but the detailed mechanism of this process remains unclear. We conducted a comprehensive DNA microarray study of the human HSC line LX-2 treated with deoxycholic acid (DCA), a secondary unconjugated BA. Additionally, LX-2 cells were exposed to nine BAs and studied using immunofluorescence staining, enzyme-linked immunosorbent assay, and flow cytometry to examine the mechanisms of HSC activation. We focused on the tumor necrosis factor (TNF) pathway and revealed upregulation of genes related to nuclear factor kappa B (NF-κB) signaling and senescence-associated secretory phenotype factors. α-Smooth muscle actin (α-SMA) was highly expressed in cells treated with secondary unconjugated BAs, including DCA, and a morphological change associated with radial extension of subendothelial protrusion was observed. Interleukin-6 level in culture supernatant was significantly higher in cells treated with secondary unconjugated BAs. Flow cytometry showed that the proportion of cells highly expressing α-SMA was significantly increased in HSCs cultured with secondary unconjugated BAs. We demonstrated that secondary unconjugated BAs induced the activation of human HSCs.

Ectopic pancreatic adenocarcinoma in Meckel's diverticulum: a case report.

BACKGROUND: Malignant neoplasms arising from Meckel's diverticulum are rare and an adenocarcinoma in Meckel's diverticulum originating from ectopic pancreatic tissue is even rarer. Herein, we report a patient with an ectopic pancreatic adenocarcinoma in Meckel's diverticulum who was successfully treated with surgery and chemotherapy. CASE PRESENTATION: A woman in her sixties presented to another hospital with abdominal pain. Plain computed tomography suggested an abdominal tumor and she was referred to our hospital. Enhanced computed tomography revealed a 23-mm low-density tumor in the abdominal cavity. Surgery was performed with a tentative diagnosis of a mesenteric tumor, such as a gastrointestinal stromal tumor, schwannoma, or lymphoma. First, we inspected the peritoneal cavity with a laparoscope. This revealed numerous nodules in the small bowel mesentery, suggesting peritoneal dissemination. A 20-mm-diameter white tumor was found in the small intestine and diagnosed as a small intestinal cancer. The small intestine was partially resected laparoscopically through a small skin incision. The patient's postoperative course was uneventful, and she was discharged on postoperative day 9. Pathological examination revealed well-differentiated adenocarcinoma in the small intestine. The tumor had developed from a sac-like portion protruding toward the serosal side and had a glandular structure lined with flattened atypical cells. Neither pancreatic acinar cells nor islets of Langerhans were evident, suggesting a Heinrich type 3 ectopic pancreas. The final diagnosis was an adenocarcinoma originating from an ectopic pancreas in Meckel's diverticulum. After a smooth recovery, the patient commenced chemotherapy for pancreatic cancer. CONCLUSIONS: We present a very rare case of ectopic pancreatic carcinoma in Meckel's diverticulum.

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.

Effect of pre-firing compression on the prevention of pancreatic fistula in distal pancreatectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) is a major complication of distal pancreatectomy (DP). Several procedures for resection and closure of the pancreas have been proposed; however, the rate of POPF remains high. The aims of this study were to investigate the relationship between perioperative factors and POPF and to clarify the advantages of pre-firing compression of the pancreas in the DP. PATIENTS AND METHOD: From 2008 to 2016, records of 75 patients who underwent DP were retrospectively reviewed. The relationship between the perioperative factors and clinically relevant POPF was investigated. RESULTS: Univariate analysis showed that body mass index, thickness of the pancreas, and pre-firing compression were significantly related with clinically relevant POPF. Multivariate analysis showed that the pre-firing compression was an independent factor of clinically relevant POPF (OR = 44.31, 95%CI = 3.394-578.3, P = 0.004). CONCLUSIONS: Pre-firing compression of the pancreas can prevent clinically relevant POPF in DP.

Clinical Utility of the Difficulty Scoring System for Predicting Surgical Time of Laparoscopic Liver Resection.

INTRODUCTION: Laparoscopic liver resection (LLR) has several problems, such as technical complexity and patient and tumor factors. A difficulty scoring system to preoperatively evaluate the difficulty of LLR was established at the second International Consensus Conference on Laparoscopic Liver Resection. The aim of this study was to explore the clinical usefulness of the difficulty scoring system for LLR. PATIENTS AND METHODS: From January 2010 to June 2015, the records of 78 patients who had undergone LLR were retrospectively reviewed. The patients' data were used to assign a difficulty score, and the correlations between scores and surgical outcomes were investigated. RESULTS: The mean surgical time was 256 minutes, and the mean blood loss was 168 mL. The difficulty score significantly correlated with surgical time and blood loss, but not with morbidity and postoperative hospital stay. Multivariate analysis showed that the difficulty score was an independent predictor of prolonged surgical time. CONCLUSIONS: The difficulty score was found to be an effective predictor of surgical time for LLR.

Benefit of laparoscopic liver resection in high body mass index patients.

AIM: To explore the impact of body mass index (BMI) on surgical outcomes in patients undergoing laparoscopic liver resection (LLR). METHODS: From January 2010 to February 2015, sixty-eight patients who underwent primary partial liver resection in our institute were retrospectively reviewed. Surgical outcomes of LLR were compared with those of open liver resection (OLR). In addition, we analyzed associations with BMI and surgical outcomes. RESULTS: Among 68 patients, thirty-nine patients underwent LLR and 29 were performed OLR. Significant difference in operation time, blood loss, and postoperative hospital stay was observed. There were no significant differences in mortality and morbidity in two groups. Twenty-two patients (32.4%) were classified as obese (BMI ≥ 25). A statistically significant correlation was observed between BMI and operation time, between BMI and blood loss in OLR, but not in LLR. The operation time and blood loss of OLR were significantly higher than that of LLR in obese patients. Open liver resection and BMI were independent predictors for prolonged operation time and increased blood loss in multivariate analysis. CONCLUSION: The present study demonstrated that BMI had influenced to surgical outcomes of OLR. LLR was less influenced by BMI and had great benefit in obese patients.

Surgical Outcomes of Laparoscopic Liver Resection in Elderly Patients: A Comparative Study From a Single Center.

The life expectancy continues to gradually increase worldwide. Laparoscopic liver resection (LLR) was recently reported to be a relatively safe procedure for treatment of liver disease because of the development of new techniques and instruments. The aim of this study was to evaluate the surgical outcomes of elderly patients who underwent LLR. Of these 61 patients who underwent LLR in our institute from January 2010 through April 2014, 21 were aged 75 years and above (group E), and 40 were aged below 75 years (group NE). Patient characteristics were retrospectively analyzed between the 2 groups. The results showed that patient characteristics were similar between the 2 groups, although the incidence of hypertension was significantly greater among patients in group E. There were no significant differences in the incidence of postoperative complications or length of hospital stay between the 2 groups. In conclusion, LLR for elderly patients was a feasible procedure compared with nonelderly patients.