Xantohumol, a prenylated chalcone from hops (Humulus lupulus L.), has been shown to inhibit proliferation in some cancers. However, little is known regarding the effects of xanthohumol in pancreatic cancer. We have previously reported that activation of the transcription factor nuclear factor‐κB (NF‐κB) plays a key role in angiogenesis in pancreatic cancer. In this study, we investigated whether xanthohumol inhibited angiogenesis by blocking NF‐κB activation in pancreatic cancer in vitro and in vivo. We initially confirmed that xanthohumol significantly inhibited proliferation and NF‐κB activation in pancreatic cancer cell lines. Next, we demonstrated that xanthohumol significantly suppressed the expression of vascular endothelial growth factor (VEGF) and interleukin‐8 (IL‐8) at both the mRNA and protein levels in pancreatic cancer cell lines. We also found that coculture with BxPC‐3 cells significantly enhanced tube formation in human umbilical vein endothelial cells, and treatment with xanthohumol significantly blocked this effect. In vivo, the volume of BxPC‐3 subcutaneous xenograft tumors was significantly reduced in mice treated with weekly intraperitoneal injections of xanthohumol. Immunohistochemistry revealed that xanthohumol inhibited Ki‐67 expression, CD31‐positive microvessel density, NF‐κB p65 expression, and VEGF and IL‐8 levels. Taken together, these results showed, for the first time, that xanthohumol inhibited angiogenesis by suppressing NF‐κB activity in pancreatic cancer. Accordingly, xanthohumol may represent a novel therapeutic agent for the management of pancreatic cancer.

The non-alcoholic fatty liver disease occurrence rate in patients undergoing pancreatoduodenectomy is high, but in about half of these patients, non-alcoholic fatty liver disease will resolve without any enzyme supplementation. Prophylactic supplementation in the postoperative management of pancreatoduodenectomy patients should be based on risk factors, and therapeutic supplementation should be based on recovery factors.

Background The Brisbane 2000 Terminology for Liver Anatomy and Resections, based on Couinaud’s segments, did not address how to identify segmental borders and anatomic territories of less than one segment. Smaller anatomic resections including segmentectomies and subsegmentectomies, have not been well defined. The advent of minimally invasive liver resection has enhanced the possibilities of more precise resection due to a magnified view and reduced bleeding, and minimally invasive anatomic liver resection (MIALR) is becoming popular gradually. Therefore, there is a need for updating the Brisbane 2000 system, including anatomic segmentectomy or less. An online "Expert Consensus Meeting: Precision Anatomy for Minimally Invasive HBP Surgery (PAM‐HBP Surgery Consensus)" was hosted on February 23, 2021. Methods The Steering Committee invited 34 international experts from around the world. The Expert Committee (EC) selected 12 questions and two future research topics in the terminology session. The EC created seven tentative definitions and five recommendations based on the experts’ opinions and the literature review performed by the Research Committee. Two Delphi Rounds finalized those definitions and recommendations. Results This paper presents seven definitions and five recommendations regarding anatomic segmentectomy or less. In addition, two future research topics are discussed. Conclusions The PAM‐HBP Surgery Consensus has presented the Tokyo 2020 Terminology for Liver Anatomy and Resections. The terminology has added definitions of liver anatomy and resections that were not defined in the Brisbane 2000 system.

Zerumbone derived from a subtropical ginger, Zingiber zerumbet Smith, was previously reported to have antitumor growth and anti-inflammatory properties in some types of cancer. However, the effects of zerumbone against cancer angiogenesis have not been fully elucidated. In this study, we clarified the role of zerumbone in gastric cancer angiogenesis. We examined the expression of vascular endothelial growth factor (VEGF) in gastric cancer cell lines both in the basal state and following zerumbone treatment by real-time RT-PCR and enzyme-linked immunosorbent assay (ELISA). Changes in gastric cancer cell proliferation in response to zerumbone treatment were measured by WST-1 assay. Additionally, the effects of zerumbone on NF-κB activity were examined in AGS cells. Finally, the effects of zerumbone on angiogenesis in AGS cells were measured by in vitro angiogenesis assay in which human umbilical vein endothelial cells (HUVECs) and fibroblasts were cocultured with AGS cells. Among the 6 gastric cancer cell lines tested, AGS cells exhibited the highest expression of VEGF. Cell proliferation, VEGF expression and NF-κB activity in AGS cells were all significantly inhibited by zerumbone. Moreover, the tube formation area of HUVECs was increased by coculture with AGS cells, and this effect was inhibited by zerumbone. Both VEGF expression and NF-κB activity in AGS cells were reduced by treatment with zerumbone, thereby inhibiting angiogenesis. Thus, zerumbone may become a new anti-angiogenic and antitumor drug in the treatment of gastric cancer.

BackgroundThe CXCL12-CXCR4 signaling axis in malignant tumor biology has increased in importance, and these peptides are implicated in tumor growth, invasion and metastasis. The aim of our study was to examine the important role of the axis in pancreatic cancer (PaCa) cells’ relationship with stromal cells in gemcitabine-resistant (GEM-R) tumors and to confirm the effectiveness of CXCR4 antagonists for the treatment of GEM-R PaCa cells.MethodsWe established two GEM-R PaCa cell lines using MIA PaCa-2 and AsPC-1 cells. The expression of CXCR4 mRNA in PaCa cells and the expression of CXCL12 mRNA in fibroblasts were examined by reverse transcription polymerase chain reaction (RT-PCR). The expression of CXCR4 protein in PaCa cells was examined by immunosorbent assay (ELISA) and immunocytochemistry. Using Matrigel invasion assays and animal studies, we then examined the effects of two CXCR4 antagonists, AMD11070 and KRH3955, on the invasiveness and tumorigenicity of GEM-R PaCa cells stimulated by CXCL12.ResultsWe found that the expression of CXCR4 in GEM-R PaCa cells was significantly enhanced by GEM but not in normal GEM-sensitive (GEM-S) PaCa cells. In RT-PCR and ELISA assays, the production and secretion of CXCL12 from fibroblasts was significantly enhanced by co-culturing with GEM-R PaCa cells treated with GEM. In Matrigel invasion assays, the invasiveness of GEM-R PaCa cells treated with GEM was significantly activated by fibroblast-derived CXCL12 and was significantly inhibited by CXCR4 antagonists, AMD11070 and KRH3955. In vivo, the tumorigenicity of GEM-R PaCa cells was activated by GEM, and it was significantly inhibited by the addition with CXCR4 antagonists.ConclusionsOur findings demonstrate that the CXCL12-CXCR4 signaling axis plays an important role in PaCa cells’ resistance to GEM. CXCR4 expression was significantly enhanced by the exposure to GEM in GEM-R PaCa cells but not in GEM-S PaCa cells. Furthermore, CXCR4 antagonists can inhibit the growth and invasion of GEM-R PaCa cells. These agents may be useful as second-line chemotherapy for GEM-R PaCa in the future.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2340-z) contains supplementary material, which is available to authorized users.

In RY reconstruction using the OL, there were no complications associated with the anastomosis site in 100 consecutive patients, such as anastomotic leak or stenosis, indicating that it is a very useful and safe reconstruction method.

In this systematic review, we aimed to clarify the useful anatomic structures and assess available surgical techniques and strategies required to safely perform minimally invasive anatomic liver resection (MIALR), with a particular focus on the hepatic veins (HVs). Methods: A systematic review was conducted using MEDLINE/PubMed for English articles and Ichushi databases for Japanese articles through September 2020. The quality assessment of the articles was performed in accordance with the Scottish Intercollegiate Guidelines Network (SIGN). Results: A total of 3372 studies were obtained, and 59 were selected and reviewed.Due to the limited number of published comparative studies and case series, the degree of evidence from our review was low. Thirty-two articles examined the anatomic landmarks and crucial structures for approaching HVs. Regarding the direction

BackgroundLaparoscopic procedures are increasingly being applied to gastric cancer surgery, including total gastrectomy for tumors located in the upper gastric body. Even for expert surgeons, esophagojejunostomy after laparoscopy-assisted total gastrectomy (LATG) can be technically challenging. We perform the overlap method of esophagojejunostomy after LATG for gastric cancer. However, technical questions remain. Is the overlap method safer and more useful than other anastomosis techniques, such as methods using a circular stapler? In addition, while we perform this overlap reconstruction after LATG in a deep and narrow operative field, can the overlap method be performed safely regardless of body habitus? This study aimed to evaluate these issues retrospectively and to review the literature.MethodsFrom October 2005 to August 2013, we performed LATG with lymph-node dissection and Roux-en-Y reconstruction using the overlap method in 77 patients with gastric cancer. This study examined pre-, intra- and postoperative data.ResultsMean operation time, time to perform anastomosis, and estimated blood loss were 391.4 min, 36.3 min, and 146.9 ml, respectively. There were no deaths, and morbidity rate was 13%, including one patient (1%) who developed anastomotic stenosis. Mean postoperative hospitalization was 13.4 days. Surgical outcomes did not differ significantly by body mass index.ConclusionsFirst, the overlap method for esophagojejunostomy after LATG is safe and useful. Second, this method can be performed irrespective of the body type of the patient. In particular, in a deep and narrow operative field, the overlap method is more versatile than other anastomosis methods. We believe that the overlap method can become a standard reconstruction technique for esophagojejunostomy after LATG.