Etsuro Hatano

Preoperative criterion identifying a low-risk group for lymph node metastasis in intrahepatic cholangiocarcinoma

Imaging study cannot identify patients with potential low‐risk for lymph node (LN) metastasis in intrahepatic cholangiocarcinoma (ICC). The purpose of this study was to identify a low‐risk group for LN metastasis in ICC using preoperatively available factors.

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.

A proposed model for the prediction of intrahepatic covalently closed circular DNA level in patients with chronic hepatitis B: cccDNA and predictive model

We sought to create a prediction model for intrahepatic covalently closed circular DNA (IH‐cccDNA) level in chronic hepatitis B (CHB) patients and to validate the models predictive accuracy.

Necrostatin-7 suppresses RANK-NFATc1 signaling and attenuates macrophage to osteoclast differentiation

Osteoclasts play a crucial role in osteolytic bone diseases, such as osteoporosis, rheumatoid arthritis, periodontitis, Pagets disease of bone and bone metastatic tumors. Therefore, controlling osteoclast differentiation and function has been considered a promising therapeutic strategy. Here, we show that necrostatin (Nec)-7, an inhibitor of programmed necrosis, strongly suppressed receptor activator of nuclear factor (NF)-κB ligand (RANKL)-induced osteoclastogenesis and bone resorption, without compromising macrophage colony-stimulating factor (M-CSF)-supported survival and growth of osteoclast precursor cells. Accordingly, Nec-7 significantly decreased the levels of RANKL-induced osteoclastogenic marker genes, such as cathepsin K. Mechanistically, Nec-7 neither affected MAPK nor NF-κB activation; however, it strongly inhibited the RANKL receptor (RANK) to nuclear factor of activated T cells c1 (NFATc1) signaling. Lentiviral expression of RANK in bone marrow-derived macrophages significantly restored osteoclastogenesis and NFATc1 amplification in Nec-7-treated cells. In this study, we revealed that Nec-7-sensitive pathways are crucially involved in osteoclast formation and function. Investigation of the molecular mechanism(s) through which Nec-7 inhibits RANK-NFATc1 signaling axis may lead to the development of new therapeutic strategies for bone disease.

Optimal introduction of laparoscopic liver resection for Child-Pugh B: LLR for Child-Pugh B cirrhosis

Surgery for Child–Pugh B liver function is considered risky because of its high morbidity rate and the acceptable indication criteria for laparoscopic liver resection (LLR) for Child–Pugh B patients have not been identified. We conducted a retrospective cohort study to determine the optimal introduction of LLR for Child–Pugh B patients based on our single‐institute experience.

AB061. P033. A comparison of delayed gastric emptying and nutritional status after pylorus-preserving versus stomach-preserving pancreaticoduodenectomy

Background: This study was performed to compare the incidence of delayed gastric emptying (DGE), postoperative outcome and long-term nutritional status between pyloruspreserving pancreaticoduodenectomy (PPPD) and subtotal stomach-preserving pancreaticoduodenectomy (SSPPD). Methods: We retrospectively analyzed 133 patients who undergoing PPPD (n=89) or SSPPD (n=44) between March 2011 and December 2015. All cases of duodenojejunostomy in PPPD and gastrojejunostomy in SSPPD were performed antecolically. The postoperative nutritional status was explored by changes ratio in the body weight, serum total protein and serum albumin for 1 year after surgery. Results: The overall incidence of the DGE was 12%. The incidence of DGE was 13.5% (grade A: 5.6%, grade B: 4.5%, grade C: 3.4%) in PPPD group and 9.1% (grade A: 4.5%, grade B: 4.5%, grade C: 0%) in SSPPD group, and was no significant differences in both groups. The mean postoperative hospital stay was 42.8 days in the PPPD group and 37.2 days in the SSPPD group, and was no significant differences in both groups. The body weight ratio was decreased at 6 months after surgery in the SSPPD group, whereas it continued to decrease at 9 months after surgery in the PPPD group. It was gradually increased 9 months later after surgery in SSPPD group, and it was increased 12 months later after surgery in PPPD group. The serum total protein ratio and serum albumin ratio were decreased at 3 months after surgery and were gradually increased 6 months later after surgery in both groups. There were no significant differences with regard to postoperative body weight ratio, serum total protein ratio and serum albumin ratio in both groups for 1 year after surgery. Conclusions: SSPPD is equivalent outcomes in incidence of DGE and in postoperative long-term nutritional status comparing PPPD.

Clinical application of projection mapping technology for surgical resection of lung metastasis

Indocyanine green fluorescent image-guided surgery was developed to identify primary and metastatic nodules of various malignancies. However, currently, surgeons need to identify the fluorescent image on a monitor, which impedes surgical procedures. Herein, we developed a novel projection mapping device that can cast the real-time fluorescent image onto the surface of the targeted organ. We performed surgical resection of a lung metastasis of hepatoblastoma using this technique. The projection mapping technique clearly detected the pulmonary lesion, and no other lesions were identified in the ipsilateral thorax. The patient is well and free of recurrence 2 years after surgery.

Impact of Preferentially Expressed Antigen of Melanoma on the Prognosis of Hepatocellular Carcinoma

Background: Retinoids, vitamin A and its derivatives, have an antitumor effect on hepatocellular carcinoma (HCC). The function of retinoids is exerted by the complex of retinoic acid (RA) with the heterodimer of retinoid X receptor and the RA receptor. The preferentially expressed antigen of melanoma (PRAME) acts as a dominant repressor of RA signaling by binding to the complex. The significance of PRAME on the prognosis of HCC remains to be clarified. Methods: PRAME mRNA expression was examined by quantitative real-time polymerase chain reaction in both tumor and non-tumor tissues of 100 HCC patients who received surgical resection. The effect of PRAME knockdown on DR5-mediated RA transcriptional activity was examined. Results: In tumor tissues, there were significant associations among PRAME expression, clinical stage, tumor markers, and tumor numbers. In non-tumor tissues, there were significant associations among PRAME expression, overall survival, and disease-free survival. The knockdown of PRAME caused no reduction in DR5-mediated transcriptional activity of RA, suggesting that PRAME acts via other mechanisms than the DR5 RA-responsive elements. Conclusion: Our findings indicate that PRAME expression is a novel prognostic marker in HCC patients.