Takeru Matsuda

Expression of the receptor tyrosine kinase genes, Ror1 and Ror2, during mouse development.

In mammals, the Ror-family receptor tyrosine kinases consist of two structurally related proteins, Ror1 and Ror2, characterized by the extracellular Frizzled-like cysteine-rich domain and membrane proximal kringle domains. As an attempt to gain insights into their roles in mouse development, expression patterns of Ror1 and Ror2 during early embryogenesis were examined and compared. Interestingly, at early stages, Ror1 and Ror2 exhibit similar expression patterns in the developing face, including the frontonasal process and pharyngeal arches, which are derived from cephalic neural crest cells. On the other hand, they exhibit different expression patterns in the developing limbs and brain, where the expression of Ror2 was detected broadly compared with that of Ror1. At a later stage, both genes are expressed in a similar fashion in the developing heart and lung, yet in a distinct manner in the brain and eye.

Loss of mRor1 Enhances the Heart and Skeletal Abnormalities in mRor2-Deficient Mice: Redundant and Pleiotropic Functions of mRor1 and mRor2 Receptor Tyrosine Kinases

ABSTRACT The mammalian Ror family of receptor tyrosine kinases consists of two structurally related proteins, Ror1 and Ror2. We have shown that mRor2-deficient mice exhibit widespread skeletal abnormalities, ventricular septal defects in the heart, and respiratory dysfunction, leading to neonatal lethality (S. Takeuchi, K. Takeda, I. Oishi, M. Nomi, M. Ikeya, K. Itoh, S. Tamura, T. Ueda, T. Hatta, H. Otani, T. Terashima, S. Takada, H. Yamamura, S. Akira, and Y. Minami, Genes Cells 5:71–78, 2000). Here we show thatmRor1-deficient mice have no apparent skeletal or cardiac abnormalities, yet they also die soon after birth due to respiratory dysfunction. Interestingly,mRor1/mRor2 double mutant mice show markedly enhanced skeletal abnormalities compared withmRor2 mutant mice. Furthermore, double mutant mice also exhibit defects not observed in mRor2 mutant mice, including a sternal defect, dysplasia of the symphysis of the pubic bone, and complete transposition of the great arteries. These results indicate that mRor1 and mRor2 interact genetically in skeletal and cardiac development.

Pancreas preservation by the 2-layer cold storage method before islet isolation protects isolated islets against apoptosis through the mitochondrial pathway

BACKGROUND Apoptosis in isolated islets has been implicated in primary nonfunction or early graft failure after islet transplantation. Recently, pancreas preservation by the 2-layer method (TLM) before islet isolation has been proved to improve the islet yield, quality, and transplant results not only in experimental models, but also in clinical settings. We examined the influence of TLM on apoptosis of isolated islets. METHOD Rat islets freshly isolated and after pancreas preservation by TLM or conventional cold storage in University of Wisconsin solution (UW) were examined and compared. Islet apoptosis was assessed by TUNEL and annexin V assays. The apoptosis pathways involved were investigated by measurement of caspase 3, 8, and 9 activities and by immunoblotting for total and phosphorylated c-Jun NH2-terminal kinase (JNK) and p38. RESULTS Islet apoptosis in the UW group was significantly increased compared with the fresh and TLM groups. Both caspase 3 and 9 activities in the UW group were higher than in the fresh and TLM groups with an approximate increase of 2- to 3-fold. On the other hand, there was no significant difference in caspase 8 activity among these 3 groups. JNKs were strongly activated both in the TLM and UW groups; although they were not activated in the fresh group, p38 was activated to almost the same levels in these 3 groups. CONCLUSIONS Pancreas preservation by TLM before islet isolation protects isolated islets against apoptosis mainly through the mitochondrial pathway. Pancreas storage before islet isolation even with TLM triggers activation of JNKs in isolated islets.

Cranial-to-caudal approach for radical lymph node dissection along the surgical trunk in laparoscopic right hemicolectomy

Complete mesocolic excision with central vascular ligation is considered to contribute to superior oncological outcomes after colon cancer surgery [1]. For advanced right-sided colon cancer, this surgery sometimes requires lymph node (LN) dissection along the superior mesenteric vein (SMV), with division of the middle colic vessels, or their right branches, at origin [2]. Here, we present cranially approached radical LN dissection along the surgical trunk during laparoscopic right hemicolectomy. The omental bursa is first opened wide, and the gastrocolic trunk of Henle is exposed, using the right gastroepiploic vessels and the accessory right colic vein (ARCV) as landmarks. After division of ARCV, SMV and middle colic vein (MCV) are identified. After dividing MCV at its root, LN dissection along SMV is conducted in a cranial-to-caudal manner. Concurrently, the middle colic artery, or its right branch, is exposed and divided at origin. The transverse colon is then raised ventrally, and LN dissection along SMV using a cranial-to-caudal approach is again performed. The ileocolic and right colic vessels are divided at origin. The ascending and transverse mesocolon, including the pedicles, are then separated from the retroperitoneal tissues, pancreatic head, and duodenum, using a medial approach. The key characteristics in this procedure consist of easy access to pancreas, early division of ARCV and middle colic vessels at origin, and easy dissection along SMV. We performed a laparoscopic colectomy using this approach for 18 patients with right-sided colon cancer. The mean operative time and blood loss were 288 min and 83 ml, respectively. The mean number of harvested LNs was 24. There were 6 cases with positive LN metastasis. There were no recurrent cases at a median follow-up period of 24 months. We consider this approach to be safe and useful for radical LN dissection along SMV for right-sided colon cancers.

Surgical outcomes of intracorporeal circular-stapled esophagojejunostomy using modified over-and-over suture technique in laparoscopic total gastrectomy

AbstractBackground Esophagojejunostomy in laparoscopic total gastrectomy (LTG) is a technically demanding procedure. Although several methods have been reported to date, none is considered consistently reliable. We developed a simple method for intracorporeal circular-stapled esophagojejunostomy using a modified over-and-over suture technique. The surgical outcomes of our technique were evaluated in comparison with those of open total gastrectomy (OTG).MethodsFrom April 2012 to August 2014, reconstruction using this method in LTG was performed for 21 consecutive patients with gastric cancer (LTG group). Their surgical outcomes were compared with those of 27 patients with gastric cancer who underwent OTG without splenectomy (OTG group) between January 2011 and April 2014.ResultsEstimated blood loss was significantly lower, and the postoperative hospital stay was significantly shorter in the LTG group than in the OTG group. The operating time and the number of harvested lymph nodes were similar between the two groups. The incidence of overall complications did not differ significantly between the two groups. Anastomotic leakage developed in one of the 21 patients in the LTG group and in two of the 27 patients in the OTG group. Anastomotic stenosis was observed in one patient in the LTG group.ConclusionsWe consider this method as simple and feasible for most laparoscopic surgeons with basic laparoscopic suturing skills. This method might help LTG to become an accepted standard surgical option for treatment of patients with gastric cancer.

Chylous ascites as a complication of laparoscopic colorectal surgery.

Until now, no data have been available on the incidence of chylous ascites after laparoscopic colorectal surgery.

Clinical outcomes of laparoscopic surgery for transverse and descending colon cancers in a community setting.

The feasibility, safety and oncological outcomes of laparoscopic surgery for transverse and descending colon cancers in a community hospital setting were evaluated.

Laparoscopic complete mesocolic excision for right-sided colon cancer using a cranial approach: anatomical and embryological consideration

BackgroundComplete mesocolic excision (CME) with central vascular ligation (CVL) should be employed for the treatment of colon cancer patients because of its superior oncological outcomes. However, this technique is technically challenging in laparoscopic right hemicolectomy because of the anatomical complexity of the transverse mesocolon.MethodsWe focused on the embryology and anatomy of the transverse mesocolon to overcome the difficulty of this surgery. The validity and efficacy of a cranial approach in achieving CME with CVL in laparoscopic right hemicolectomy was elucidated from the embryological point of view.ResultsIn total, 28 consecutive patients with right-sided colon cancer were treated by laparoscopic right hemicolectomy using a cranial approach. There were no conversion to open surgery or switching to another approach. Using this approach, torsion and fusion of the transverse mesocolon, which occurred during embryological development, could be reversed and the complex anatomy of the transverse mesocolon could be simplified before performing CVL of colonic vessels.ConclusionsA cranial approach is considered valid and useful for CME with CVL in laparoscopic right hemicolectomy from the embryological point of view.

Impact of adjuvant radiation therapy for microscopic residual tumor after resection of extrahepatic bile duct cancer.

Objectives:The effect of adjuvant radiation therapy (RT) in extrahepatic bile duct (EHBD) cancer patients with microscopic-positive resection margins (R1 resection) is still controversial. Methods:Between January 2000 and March 2010, 52 patients with EHBD cancer underwent surgery at our institution, of whom 36 were subjected to a retrospective analysis. Eleven patients received adjuvant RT after resection [surgery (S)+RT group], which included 9 patients with R1 resection and 2 with para-aortic lymph node metastasis. Their oncological outcomes were analyzed and compared with those of the 25 patients with R0 resection who did not receive adjuvant RT (S group). Results:Patients in the S+RT group had significantly more advanced disease than those in the S group. However, there was no significant difference in disease-free survival or overall survival between the 2 groups. Median survival times for the S+RT and the S groups were 44 and 47 months, respectively, whereas the 5-year survival rates were 38.9% and 46%, respectively (P=0.707). Locoregional recurrence was less frequent in the S+RT group as compared with the S group, but the incidence of distant metastasis was unaffected by the adjuvant RT. Conclusions:Our results support the beneficial effect of adjuvant RT in EHBD cancer patients with R1 resection. This effect seems to result from an improved control of the locoregional tumor by adjuvant RT.

The learning effect of using stereoscopic vision in the early phase of laparoscopic surgical training for novices

BackgroundRecently to improve depth perception, the performance of three-dimensional (3D) laparoscopic surgeries has increased. However, the effects of laparoscopic training using 3D are still unclear. This study aimed to clarify the effects of using a 3D monitor among novices in the early phase of training.MethodsParticipants were 40 novices who had never performed laparoscopic surgery (20 medical students and 20 junior residents). Three laparoscopic phantom tasks (task 1: touching markers on a flat disk with a rod; task 2: straight rod transfer through a single loop; and task 3: curved rod transfer through two loops) in the training box were performed ten times, respectively. Performances were recorded by an optical position tracker. The participants were randomly divided into two groups: one group performed each task five times initially under a 2D system (2D start group), and the other group performed each task five times under a 3D system (3D start group). Both groups then performed the same task five times. After the trial, we evaluated the performance scores (operative time, path length of forceps, and technical errors) and the learning curves for both groups.ResultsScores for all tasks performed under the 3D system were significantly better than scores for tasks using the 2D system. Scores for each task in the 2D start group improved after switching to the 3D system. However, scores for each task in the 3D start group were worse after switching to the 2D system, especially scores related to technical errors.ConclusionsThe stereoscopic vision improved laparoscopic surgical techniques of novices from the early phase of training. However, the performance of novices trained only by 3D worsened by changing to the 2D environment.