Kazuhiro Suzumura

Fascin, a novel marker of human hepatic stellate cells, may regulate their proliferation, migration, and collagen gene expression through the FAK-PI3K-Akt pathway

Fascin is a component of actin bundles and may regulate various cellular events. The expression and function of fascin in human hepatic stellate cells (HSCs) has remained largely uncharacterized. Fascin expression in human liver tissue was studied using immunohistochemistry. To identify cells expressing fascin, double immunofluorescent staining with vimentin, α-smooth muscle actin (α-SMA), or fibulin-2 was performed and analyzed with confocal microscopy. In culture experiments, fascin expression and the phosphorylation of focal adhesion kinase (FAK) and Akt in LX-2 cells, a cell line of human HSCs, were investigated using western blot. Specific siRNAs were used to reduce the expression of fascin in LX-2 cells. Proliferation and migration were assayed with a CyQuant assay kit and a Matrigel-coated culture insert system, respectively. Levels of matrix metalloproteinase (MMP)-2 and collagen mRNAs were examined using quantitative RT-PCR. Immunohistochemistry revealed the expression of fascin along sinusoids and overlapping with vimentin and α-SMA in both non-fibrotic and fibrotic liver tissue, but it was almost absent in periportal myofibroblastic cells and did not colocalize with fibulin-2, a marker of portal myofibroblasts. In addition, fascin immunoreactivity was almost undetectable in septa of fibrotic human liver tissue. The expression of fascin in LX-2 cells was confirmed using western blot. Two different specific siRNAs against fascin significantly reduced the number of viable LX-2 cells to 65% compared with control cultures and downregulated the mRNAs levels of types I and III collagen and MMP-2 to 62%, 65%, and 70% of control levels, respectively. This condition also reduced the migration activity of LX-2 cells to 46% of control cells and the phosphorylation level of both FAK and Akt. Fascin may be an excellent novel marker of human HSCs that distinguishes HSCs from periportal myofibroblasts. Fascin may regulate functions of human HSCs through the FAK-phosphoinositide 3-kinase-Akt pathway.

Randomized Controlled Trial of Pancreaticojejunostomy versus Stapler Closure of the Pancreatic Stump During Distal Pancreatectomy to Reduce Pancreatic Fistula.

Objectives: The aim of this study was to evaluate in a multicenter randomized controlled trial (RCT) whether pancreaticojejunostomy (PJ) of pancreatic stump decreases the incidence of pancreatic fistula after distal pancreatectomy (DP) compared with stapler closure. Background: Several studies reported that PJ of pancreatic stump reduces the incidence of pancreatic fistula after DP. However, no RCT has confirmed the efficacy of PJ of pancreatic stump. Methods: One hundred thirty-six patients scheduled for DP were enrolled in this study between June 2011 and March 2014 at 6 high-volume surgical centers in Japan. Enrolled patients were randomized to either stapler closure or PJ. The primary endpoint was the incidence of pancreatic fistula based on the International Study Group on Pancreatic Fistula criteria. This RCT was registered with ClinicalTrials.gov (NCT01384617). Results: Sixty-one patients randomized to stapler and 62 patients randomized to PJ were analyzed by intention-to-treat. Pancreatic fistula occurred in 23 patients (37.7%) in the stapler closure group and 24 (38.7%) in the PJ group (P = 0.332) in intention-to-treat analysis. The incidence of clinically relevant pancreatic fistula (grade B or C) was 16.4% for stapler closure and 9.7% for PJ (P = 0.201). Mortality was zero in both groups. In a subgroup analysis for thickness of pancreas greater than 12 mm, the incidence of clinically relevant pancreatic fistula occurred in 22.2% of the patients in the stapler closure group and in 6.2% of the PJ group (P = 0.080). Conclusions: PJ of the pancreatic stump during DP does not reduce pancreatic fistula compared with stapler closure.

Minimally invasive laparoscopic liver resection: 3D MDCT simulation for preoperative planning

BACKGROUND/PURPOSE Laparoscopic liver resection has not gained wide acceptance compared with other laparoscopic procedures. We evaluated the impact of simulated surgery using data from multidetector CT scanning on planning for laparoscopic hepatectomy. METHODS The hepatectomy simulation system was programmed to perform three-dimensional reconstruction of the vasculature and to calculate the liver resection volume and surgical margin. In 35 patients undergoing laparoscopic hepatectomy or laparoscopy-assisted hepatectomy, the liver resection volume and margin were estimated by simulation preoperatively. Then, the estimated values were compared with the actual resected liver weight and margin. RESULTS Three-dimensional reconstruction allowed stereoscopic identification of the tumor-bearing portal vein and draining vein. The predicted liver resection volume and margin both showed a significant correlation with the actual values: the mean difference was 21 mL (P < 0.0001) and 1.3 mm (P < 0.01), respectively. Preoperative planning based on simulated resection facilitated laparoscopic mobilization of the liver and mini-laparotomy resection of a large tumor located in the upper right lobe. CONCLUSIONS Three-dimensional simulation of hepatectomy facilitated intraoperative identification of the vascular anatomy, and accurately predicted the resected liver volume and surgical margin. This simulation method should contribute to preoperative planning for safe and curative laparoscopic hepatectomy.

Multivariate logistic regression analysis for prediction of clinically relevant pancreatic fistula in the early phase after pancreaticoduodenectomy

Postoperative pancreatic fistula (PF) remains a major complication after pancreaticoduodenectomy (PD). We aimed to investigate the predictors of clinically relevant PF after PD.

Primary squamous cell carcinoma of the liver: an uncommon finding in contrast-enhanced ultrasonography imaging.

Primary squamous cell carcinoma (SCC) of the liver is rare tumor with an unfavorable prognosis. We report a case of advanced primary SCC of the liver arising adjacent to a nonparasitic liver cyst, invading into the right diaphragm and the right lung tissue. Contrast-enhanced ultrasonography (CE-US) demonstrated unique enhancement in the late vascular phase, which was incompatible with those observed in hepatocellular carcinoma, cholangiocellular carcinoma, or metastatic adenocarcinoma. The patient underwent surgical resection of the tumor followed by systemic chemotherapy with 5-fluorouracil (5-FU) and cisplatin (CDDP), while radiation chemotherapy was not applied because of relatively poor performance status. Although postoperative image analysis revealed no recurrence 4 months later, the patient died 13 months after the operation from recurrence. Immunohistological analysis of the resected specimen revealed that this SCC contained many capillary endothelial vessels expressing CD31 or CD34, possibly reflecting the unique imaging pattern in the late vascular phase of CE-US, which has been reported in choangiolocellular carcinoma. In addition, we reviewed which kind of treatment would be suitable for advanced hepatic primary SCC in the literature. From the review, it could be proposed that a combination of radiation therapy, systemic chemotherapy (5-FU and CDDP) and surgical resection, if possible, is appropriate for advanced primary SCC of the liver.

Laparoscopic management of giant splenic true cyst with partial splenectomy: A case report

Non‐parasitic splenic cysts are relatively rare, and the optimal surgical treatment for them remains controversial. Laparoscopic unroofing is a relatively safe and easy technique, but a significant number of recurrences has been reported. Thus, complete cystectomy with partial splenectomy is recommended by several surgeons. However, patients sometimes suffer from intraoperative bleeding. Here, we report a patient with a giant non‐parasitic splenic cyst who underwent subtotal cystectomy with partial splenectomy. After the dissection of the vessels circulating the upper pole at the splenic hilum, the resection line of the splenic parenchyma was on the ischemic side of the cyanotic demarcation line. A vessel sealing system and laparoscopic coagulation shears were used for the resection. We intentionally left about 10% of the cyst wall to avoid bleeding from the non‐ischemic splenic parenchyma and remaining vessels. No recurrence has been detected after 6 months of observation. We believe this method could be a useful alternative procedure for the treatment of non‐parasitic splenic cysts and preservation of the splenic parenchyma.

Salvage treatment of laparoscopic cholecystectomy‐associated bile duct stenosis combining laparoscopic and endoscopic procedures: A case report

The incidence of laparoscopic cholecystectomy (LC)‐associated bile duct injury has reached a steady state despite learning curve effect. Herein we report the case of a 74‐year‐old Japanese man who suffered from bile duct stenosis and stones after LC. The stenosis was due to stricture caused by surgical clips used inappropriately during LC. We planned a salvage treatment combining laparoscopic and endoscopic approaches. At laparoscopic observation, the clips had already invaded the right side of the bile duct; minimal absorbable suture was performed after all the clips were removed. The bile duct stenosis was then endoscopically dilated and the biliary stones were successfully removed. For the recurrent biliary stenosis after discharge, endoscopic balloon dilation was performed and multiple plastic stent tubes were placed. The stent tubes were removed 4 months later, and the patient has had no symptoms for 1 year. A combined laparoscopic and endoscopic approach was useful for the salvage treatment of LC‐associated bile duct stenosis.

Multifocal Mass Lesions in Autoimmune Pancreatitis

A 59-year-old male patient with jaundice was referred to our hospital because of mass lesions in the pancreatic head and tail. An immunological examination revealed an elevated serum IgG4 level. Computed tomography showed two clear boundary mass lesions in the pancreatic head and tail. Magnetic resonance imaging showed that the mass lesions exhibited low intensity on T1-weighted images and iso-intensity on T2-weighted images. Magnetic resonance cholangiopancreatography showed an obstruction of the main pancreatic duct in the pancreatic head and tail. The possibility of malignant tumors could not be ruled out; therefore, we performed total pancreatectomy. A histopathological examination of the nodular lesions revealed severe lymphoplasmacytic infiltration and inflammatory change around the pancreatic ducts. Immunohistochemistry revealed diffuse infiltration of IgG4-positive plasma cells in the nodules. According to these pathological findings, we diagnosed the patient with IgG4-related multifocal mass lesions of autoimmune pancreatitis (AIP). It is difficult to distinguish between focal type AIP and pancreatic cancer. We herein report a rare case of multifocal mass lesions in AIP and include bibliographical comments.

Successful laparoscopic extirpation of peritoneal dissemination after hepatectomy for ruptured hepatocellular carcinoma.

Clinically, peritoneal dissemination of hepatocellular carcinoma (HCC) rarely occurs. We herein report a case that had a good outcome following laparoscopic extirpation of peritoneal dissemination after hepatectomy for ruptured HCC. A 66‐year‐old man underwent central bisectionectomy 12 days after emergency transcatheter arterial embolization for a ruptured HCC. Thereafter, pulmonary resection was performed twice for lung metastasis. About 8 months after the second pulmonary resection, a mass lesion was detected at the left subphrenic space on CT and 18F‐fluorodeoxyglucose PET scans. We made a diagnosis of peritoneal dissemination of HCC, and laparoscopic extirpation was performed. The patient is now doing well without any signs of recurrence 2 years after the last operation. Laparoscopic surgical resection for peritoneal dissemination that develops after hepatectomy for HCC may have a beneficial effect as a less‐invasive approach and may improve the prognosis in select patients.

Delayed Arterial Hemorrhage After Pancreaticoduodenectomy

Delayed arterial hemorrhage is a rare complication of pancreaticoduodenectomy that is associated with a high mortality and has no standard management. Between 2000 and 2011, 204 pancreaticoduodenectomies were performed, and there were 3 cases of delayed arterial hemorrhage. We reviewed the role of endoscopy, laparotomy, and interventional radiology the management of delayed hemorrhage. One patient presented with intraluminal bleeding and upper gastrointestinal endoscopy failed to identify the bleeding site. Two patients presented with bleeding from the drain tube. Laparotomy was performed in the patient with intraluminal bleeding and interventional radiology was employed for the other 2 patients. There was no hemorrhage-related mortality or rebleeding, but the patient who underwent laparotomy developed sepsis. Endoscopy may have no role in the initial management of delayed arterial hemorrhage after pancreaticoduodenectomy. Interventional radiology is less invasive compared with laparotomy, and may be considered as the first-line treatment for delayed arterial hemorrhage in pancreaticoduodenectomy patients.