Hideaki Sueoka

Blockage of CXCR2 suppresses tumor growth of intrahepatic cholangiocellular carcinoma

BACKGROUND/AIMS Complete operative resection is the only approach to cure for intrahepatic cholangiocellular carcinoma (ICC), but the diseases prognosis is notably poor. A novel therapeutic approach is urgently required. CXC chemokine receptor 2 (CXCR2) has been associated with tumorigenesis and metastasis in human cancers. In this study, we investigated the suppressive effect of ICC growth by blocking CXCR2. MATERIAL AND METHODS The role of CXCR2 was estimated using the human ICC cell lines, RBE and SSP25. CXCR2 small interfering RNA (siRNA) and an antagonist (SB225002) were used to block CXCR2. Proliferation assays, migration assays, and invasion assays were performed to confirm the suppressive effect of blocking CXCR2. Subcutaneous SSP25 tumors were established in athymic nude mice, and the mice were given SB225002. The expression of CXCR2 in ICC was determined by immunohistochemical staining of 34 ICC specimens. We investigated the relationship between CXCR2 expression and prognosis in ICC. RESULTS The prognosis of patients who had higher CXCR2 expression in ICC was significantly poor (P = .004). CXCR2 siRNA treatment significantly suppressed CXCR2 expression in both RBE and SSP25. Cell proliferation, migration, and invasion were significantly suppressed by both CXCR2 siRNA and SB225002 compared with the control group. SB225002 also suppressed the growth of transplanted subcutaneous tumors (P = .02) CONCLUSION: Our results demonstrated that blocking CXCR2 clearly suppressed the development of ICC. Blocking CXCR2 may be a promising therapeutic approach for ICC.

Parenchyma-preserving hepatectomy based on portal ramification and perfusion of the right anterior section: preserving the ventral or dorsal area

Anatomical hepatectomy aims to eliminate the spread of malignant tumor cells via portal vein systemically. An anatomical concept of the right anterior section (RAS) and preservation of the liver parenchyma within the RAS has been proposed.

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.

Immunohistochemical characterization of cancer-associated fibroblasts at the primary sites and in the metastatic lymph nodes of human intrahepatic cholangiocarcinoma

Cancer-associated fibroblasts (CAFs) are an important constituent of the cancer stroma. In intrahepatic cholangiocarcinoma (ICC), the features of CAFs at the primary site and in the metastatic lymph nodes (Met-LNs) and their origin have been unclear. In the present study, we characterized CAFs at the primary site (n = 42) and in the Met-LNs (n = 10) of human ICC by immunohistochemistry using potential molecular markers of CAFs, portal fibroblasts (PFs), hepatic stellate cells (HSCs), and bone marrow-derived fibrocytes (BMDFs). At the primary site, the stroma was strongly positive for α-smooth muscle actin (α-SMA; marker for CAFs), platelet-derived growth factor receptor-β (PDGFR-β) (common marker for HSCs and PFs), fibulin-2, and thymus cell antigen-1 (Thy-1; PF marker), whereas immunoreactivity for fascin (HSC marker) was scarce. Most of the α-SMA-positive cells were found to express PDGFR-β, Thy-1, and fibulin-2 by double immunostaining. A small population of BMDF marker-positive (α-SMA+CD45+CD34+) cells was found by triple immunostaining. In the micro-Met-LNs, α-SMA-positive cells were absent in cancer aggregates of the LN sinus, whereas they were present in the invasion area of cancer cells from the LN sinus to the LN parenchyma. In the macro-Met-LNs, there were abundant α-SMA-positive cells that were also positive for PDGFR-β and Thy-1 but negative for fibulin-2 and fascin. Thus, regarding the expression of molecular markers, CAFs at the primary site of ICC are similar to PFs and different from those of HSCs or CAFs in the Met-LNs. CAFs at the primary sites and in the Met-LN are thought to be derived from PFs/BMDFs and resident cells of LNs, respectively.

Difficulty Achieving a Preoperative Diagnosis of IgG4-Related Sclerosing Cholangitis

A 75-year-old male was admitted to our hospital because of bile duct stenosis. He had no medical history of autoimmune disease. The level of tumor markers, serum IgG, and IgG4 were within normal ranges. Computed tomography showed perihilar and distal bile duct stenosis and wall thickening without swelling or abnormal enhancement of the pancreas. Endoscopic retrograde cholangiopancreatography showed perihilar and distal bile duct stenosis. A biopsy and cytology from the distal bile duct stenosis suggested adenocarcinoma, and cytology from the perihilar bile duct also suggested adenocarcinoma. A preoperative diagnosis of perihilar and distal bile duct cancer was made, and the patient underwent left hepatectomy and pancreaticoduodenectomy. Resected specimens showed wall thickening in the perihilar and distal bile duct; however, tumors were unclear. A histopathological examination revealed lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis in the perihilar and distal bile ducts. Immunohistochemistry revealed diffuse infiltration of IgG4-positive plasma cells in the perihilar and distal bile ducts. Lymphoplasmacytic infiltration, inflammatory change, storiform fibrosis, and obliterative phlebitis were shown in the pancreas. A final diagnosis of IgG4-related sclerosing cholangitis (IgG4-SC) with autoimmune pancreatitis was made. We herein report a case in which a preoperative diagnosis of IgG4-SC was difficult due to normal serum IgG4 levels and no obvious pancreatic lesion.

A Surgical Case of Synchronous Double Primary Cancers of the Bile Duct and Pancreas

Abstract A 54-year-old female was seen at another hospital because of jaundice. CT showed an unclear boundary and a poorly enhanced mass lesion in the pancreatic body, measuring 28 mm in diameter. MRCP showed stenosis of the lower bile duct and the main pancreatic duct in the pancreatic body and slight dilatation of the main pancreatic duct in the pancreatic tail. According to these findings, the preoperative diagnosis was synchronous double cancers of primary lower bile duct cancer and pancreatic body cancer. We performed pylorus-preserving pancreaticoduodenectomy with splenic artery and vein resection. A histopathological examination revealed that the lower bile duct tumor was moderately differentiated tubular adenocarcinoma, and the pancreatic body tumor was moderately differentiated tubular adenocarcinoma. These two tumors showed no histopathological continuity. According to these pathological findings, we diagnosed the patient with synchronous double cancers of primary lower bile duct cancer and panc...

Hepatectomy for Hilar Cholangiocarcinoma with Right-Sided Ligamentum Teres Using a Hepatectomy Simulation System

Right-sided ligamentum teres (RSLT) is a rare congenital anomaly often accompanied by variation of the hepatic vasculature. We herein report a surgical case of a hilar cholangiocarcinoma with RSLT in whom preoperative hepatectomy simulation proved useful for understanding the anatomical structure of the liver. A 78-year-old male with obstructive jaundice was referred to our department for further examination. The patient was suspected of having a hilar cholangiocarcinoma originating from the left hepatic bile duct by contrast-enhanced computed tomography (CT), and CT also showed right umbilical portion (RUP). Three-dimensional images of the hepatic vasculature and biliary system reconstructed using a hepatectomy simulation system suggested that all portal branches ramified from RUP were right paramedian branches, and three leftward portal branches from these ran parallel to the peripheral bile ducts confluent with the left hepatic bile duct, where the tumor was present. Hepatic resection of part of the ventral area of the right paramedian sector and left hemiliver was performed along the demarcation line drawn after clamping the portal branches; the ratio of estimated liver resection volume was 28.9%. After the operation, bile leakage occurred. However, the leakage was treated with percutaneous drainage alone, and the patient was discharged 77 days after the operation. The patient is doing well without any signs of recurrence 21 months after the operation. The vascular and biliary anatomy in patients with RSLT is complicated and should be evaluated in detail preoperatively using a hepatectomy simulation system.