Laparoscopic pancreatectomy in Kyushu University and in Japan

Abstracts / Pancreatology 16 (2016) S1eS192

S4-5. Laparoscopic distal pancreatectomy: Effects of standardization Tadahiro Goto, Hirochika Toyama, Sadaki Asari, Sachio Terai, Masahiro Kido, Tetsuo Ajiki, Takumi Fukumoto, Yonson Ku Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University, Japan Background: With the approval of the ethical committee of our institute, we introduced laparoscopic pancreas surgery (LPS) in March, 2007. Indications of LPS in our center are benign, borderline and low-grade malignant tumors. Object: To report our experience with LPS in order to introduce a safe procedure, indicating how to inherit and develop the surgical technique with LPS. Methods: We reviewed our LPS data, and we retrospectively compared perioperative outcomes of LAP-DP. We classified three groups (A: initial group, n¼11, B: second group, n¼13, C: recent group, n¼10). Surgical procedure: In Lap-DP, points of surgical procedure are 1) to make effective visual development by using tapes tugging stomach and pancreas 2) to use clamping device for pre-compression before dissecting pancreas parenchyma. Results: The number of subjects with IPMN, MCN, NET, SCN, and others were 31, 16, 9, 5 and 8, respectively. Median age was 60 and mean tumor size was 3.5cm. We performed 1 laparoscopic-assisted distal pancreatectomy (extraperitoneal resection), 8 HALS-DP, 1 HALS-SPDP, 53 LAP-DP, and 6 LAP-SPDP. The median operative time was 339 minutes and hemorrhagic volume was 177 ml. Postoperative pancreatic fistula (grade B of the ISGPF classification) occurred in 12 (17%) patients. The mean postoperative number of days taken to initiate oral food intake was 3.3, and the mean length of the hospital stay was 16.6 days. No recurrent tumor was observed. The median operating times for the group A, group B and group C were 335 min, 391 min and 279 min, respectively. The median blood loss for the group A, group B and group C were 184 ml, 100 ml and 45 ml, respectively. Conclusion: Setting a standardized safe procedure is the key and an effective way of transmitting the surgical technique from generation to generation.

S4-6. The tips of laparoscopic spleen-preserving distal pancreatectomy without preservation of splenic vessels (Warshaw technique) Shinichiro Ono, Tamaotsu Kuroki, Amane Kitasato, Masaaki Hidaka, Akihiko Soyama, Kouji Natsuda, Fumihiko Fujita, Kengo Kanetaka, Susumu Eguchi Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan Background: In our institution, Laparoscopic Warshaw technique (LWT) is a first choice for low grade malignant tumor close to splenic vessels and/or in case difficult to dissect from splenic vessels. Warshaw technique is considered to cause the splenic infarction and perigastric varices formation. In this study, we show the tips of LWT for reducing the splenic infarction and perigastric varices formation. Methods: Firstly, the pancreas was mobilized from the median toward the splenic hilum. Splenocolic ligament and left gastroepiploic vessels (LGEVs) were preserved as well as the short gastric vessels. Usually, LGEVs are divided from inferior pole of splenic vessels. The tip of LWT is to preserve this arcade from the view point of splenic circulation. Between February 2007 and February 2016, a total of 19 patients underwent LWT. Results: The median operative time, blood loss, and hospital stay were 295 min (201-512), 200 gr (5-3250) and 16 (8-29) days. There was no grade B or C pancreatic fistula. All patient's platelet counts turned to normal within one month. Six patients (32%) with splenic partial infarction and 2 patients (12%) with gastric varices were detected but they haven't been needed any treatments. Michels et al. classified the distribution of splenic

S23

vessels as distributed type (vessels spread to splenic hilum like fan shape) and magistral type (vessels spread to splenic hilum narrowly) at splenic hilum. In our study, 16 patients were distributed type and 3 patients were magistral type. Three of 16 patients (23%) were developed splenic infarction in distributed type. On the other hands, all magistral patients (100%) showed splenic infarction. Preoperative 3-D images make it possible to decide the accurate transection line of vessels. Conclusions: The most important point of the Warshaw procedure is to preserve the splenic hilum arcade to reduce the splenic infarction and perigastric varices formation.

S4-7. Laparoscopic distal pancreatectomy with or without splenectomy: Spleen and splenic vessels preservation does not increase morbidity Kazuhiro Suzumura, Toshihiro Okada, Yasukane Asano, Hisashi Kosaka, Tadamichi Hirano, Naoki Uyama, Ikuo Nakamura, Yuichi Kondo, Seikan Hai, Hideaki Sueoka, Akito Yada, Tomohiro Okamoto, Ami Kurimoto, Jiro Fujimoto Department of Surgery, Hyogo College of Medicine, Japan Background/aims: The indications for laparoscopic spleen-preserving distal pancreatectomy (LSPDP) and its morbidity compared with laparoscopic distal pancreatectomy with splenectomy (LDPS) are ill-defined. This study aimed to evaluate the safety, feasibility and outcome of LSPDP. Methods: Between January 2010 and February 2016, 17 patients underwent LSPDP with conservation of the splenic artery and vein or LDPS in our institution. LSPDP with conservation of the splenic artery and vein and LDPS were performed in 13 and 4 patients. Their clinical data and outcomes of two procedures were compared by statistical analysis and reviewed retrospectively. Results: There were no significant differences in age, gender, American society of anesthesiologist (ASA) score, body mass index (BMI) and blood loss between the LSPDP and LDPS groups. The mean tumor size (2.9 vs 7.5cm, P <0.05) and mean operative time (251 vs 374 minutes, P<0.05) were greater in the LDPS than in the LSPDP group. Peak platelet level in the LSPDP and LPDS groups were on 11 and 15 postoperative days, respectively. In the both groups, postoperative peak platelet counts ratio was significant high compared with preoperative platelet counts ratio. However, 1, 3, 6 and 12 months after operation, platelet counts ratio was not significant differences compared with preoperative platelet counts ratio. One patient (25%) with postoperative portal vein thrombosis in the LDPS group compared with none of the patients in the LSPDP group. The differences in the complications included pancreatic fistula and intra-abdominal infection between the two groups were not significant. Moreover there were not postoperative bleeding, re-operation and mortality in both groups. Conclusion: LSPDP with conservation of the splenic artery and vein was a safe and feasible option for benign or low-grade malignant tumors in the distal pancreas. Splenic conservation does not significantly increase the morbidity of the procedure.

S4-8. Laparoscopic pancreatectomy in Kyushu University and in Japan Masafumi Nakamura Department of Surgery and Oncology, Kyushu University, Japan The national health insurance started cover LDP in 2012 in Japan and we have performed more than 2,500 laparoscopic pancreatectomies through 2013. With regard to LDP, we have performed national wide survey to unveil the clinical advantages of LDP comparing to open method using propensity score matching. The study revealed that LDP was superior to open method in terms of several clinical points including overall morbidity and pancreatic fistula at clinical grades. Vessels-preserving LDP (VP-LDP) is

S24

Abstracts / Pancreatology 16 (2016) S1eS192

used as a primarily method as long as it is applicable. Peri-firing compression method (PFC), also called as slow-flattening method, is generally used for closing pancreatic stump. The risk of pancreatic fistula depends on the thickness of the pancreatic stump, which correlate with BMI. These fact shows that closure of pancreatic stump by a stapler might be suitable for Japanese patients, who are generally lean. We, in Kyushu University, subjected pancreatic stump more than 25mm in thickness to modified DuVal anastomosis. Most of LPDs were performed as hybrid operations. The excision of pancreatic head and duodenum was performed by a laparoscopic method, the P-J anastomosis by an open method, and the reconstruction of biliary tree by a laparoscopic method. I demonstrate the current status of laparoscopic pancreatic surgery in Japan and show our current method with special reference to the points mentioned above.

S5-KL1. Relative contribution of trypsin and inflammation in pancreatitis Ashok K. Saluja

cytokines through JAK2/STAT3 signaling in pancreatic acinar cells. We also found that there are crosstalks among core inflammatory mediators including mitogen-activated protein kinases, NF-kB, AP-1, and JAK/STAT in pancreatic acinar cells upon cerulein stimulation. In addition, treatment with peroxisome proliferator activated receptor-gamma ligands such as 15d-PGJ2 and troglitazone suppress the activation of JAK2/STAT3 and the expression of pro-inflammatory cytokines in cerulein-stimulated cells. Since pancreatic stellate cells produce fibrotic proteins and facilitate cell proliferation and migration of cancer cells to the different sites by producing cytokines, growth factors and metalloproteinases, pancreatic stellate cells may be involved in the pathogenesis of chronic pancreatitis and pancreatic cancer. We found that expression of inflammatory cytokines (MCP-1, CX3CL1) and fibrotic proteins (a-SMA, desmin, COL1A1, TGF-b1) are mediated with NF-kB activation in pancreatic stellate cells exposed to TNF-a. Intracellular and mitochondrial levels of ROS increased with loss of mitochondrial membrane potential in pancreatic stellate cells exposed to TNF-a. In conclusion, the activations of NADPH oxidase and JAK2/STAT3 are important for oxidative stress-induced inflammatory and fibrotic pathways. Mitochondrial disruption may be one of the underlying mechanisms to induce oxidative stress in the pathogenesis of pancreatitis.

Department of Surgery and Sylvester Comprehensive Cancer Center, University of Miami, USA During experimental initiation of pancreatitis, both trypsin and inflammatory pathway activation is observed concurrently. The relative contribution of these events to acinar cells injury and development of pancreatitis is not clear. The studies using inhibitors which block trypsin or inflammation activation were unable to yield unambiguous answers because of nonspecific effects. Mouse pancreas expresses multiple forms of trypsin of which T7, T8, T10 and T20 are expressed. In our studies, mice lacking trypsin isoform T7 do not show trypsin activation in response to supramaximal stimulation and provides an ideal tool for understanding the relative contribution of these initiating events. Deletion of T7 significantly reduced the total trypsinogen contents but did not affect physiologic function. Absence of trypsinogen activation in T7 (-/-) mice led to near complete inhibition of acinar cell death in vitro and a 50% reduction in acinar necrosis during acute pancreatitis progression. However, T7 (-/-) mice had similar degrees of local and systemic inflammation during acute pancreatitis progression and comparable levels of intra-acinar NF-kB activation. Furthermore our studies indicate that induction and severity of chronic pancreatitis is independent of trypsin activation. Compared with pancreatic tissues from wild-type mice, those from T7 (-/-) mice had similar levels of atrophy, histomorphologic features of chronic pancreatitis, and chronic inflammation. All samples had comparable intra-acinar activation of nuclear factor (NF) -kB, a transcription factor that regulates the inflammatory response, immediately after injection of caerulein. Conclusions: Activation of inflammatory pathways is not dependent on trypsin activation. Inflammatory pathways contribute to pancreatic necrosis. Absence of intra-acinar trypsin activation reduced pancreatic necrosis during acute pancreatitis progression but had no effect on chronic pancreatitis.

S5-KL3. Metabolic stressors and pancreatic disease Stephen Pandol 1, 2, 3, Mark Goodarzi 1, Guido Eibl 2, Richard Waldron 1, 2, 3, Anna Gukovskaya 2, 3, Kristine Monroe 4, V. Wendy Setiawan 4, Vay Liang Go 2, 3, Baoan Ji 6, Mouad Edderkaoui 1, 2, 3, Elham Afghani 1, Marc Goodman 1, Christie Jeon 1, Bechien Wu 5, Aurelia Lugea 1, 2, 3 1

Cedars-Sinai Medical Center, USA University of California, USA 3 Department of Veterans Affairs, USA 4 University of Southern California, USA 5 Kaiser Permanente, Los Angeles, USA 6 Mayo Clinic, Rochester, USA 2

The incidence of pancreatic diseases including pancreatitis and pancreatic adenocarcinoma is modified by both genetic and environmental factors. Further, genetic variation either germ line or acquired through mutation alters the susceptibility to environmental factors. A determination of the relative impact and mechanisms of effect of these factors alone and in combination on pancreatic diseases is essential for developing prevention, early diagnosis and treatment strategies. We describe our combined approach to assess factors regulating disease formation in human populations; utilizing the information to create animal models for investigation of mechanisms of the effects of the factors; and testing inventions that alter factors regulating disease formation in human clinical trials to determine the effects on outcome.

S5-1. S5-KL2. Signaling in pancreatic acinar and stellate cells in the pathogenesis of pancreatitis Hyeyoung Kim Department of Food and Nutrition, Yonsei University, South Korea Pancreatic acinar cells and pancreatic stellate cells are important target cells in the development of pancreatic inflammation and fibrosis. When activated by hormones such as cholecystokinin and cytokines such as tumor necrosis factor a (TNF-a), the cells induce various inflammatory cytokines and fibrotic proteins. We previously showed that cerulein, a cholecystokinin analogue, stimulated NADPH oxidase and induced expression of pro-inflammatory

The roles of cathepsin B, D, and L during acute and chronic pancreatitis in mice Masaki Ohmuraya Institute of Resource Development and Analysis, Kumamoto University, Japan Cathepsin B, D, and L (CB, CD, and CL) are the major lysosomal proteases and are widely distributed in the cells of various mammalian tissues. These cathepsins participates in various physiological events such as regulation of programmed cell death, activation of enzymatic precursors, and metabolic degradation of intracellular proteins through autophagy. Autophagy is a major pathway for degradation of cytoplasmic proteins and organelles, and has been implicated in the pathogenesis of acute and chronic pancreatitis.