A novel locally operated master-slave robot system for single-incision laparoscopic surgery

Purpose: Single-incision laparoscopic surgery (SILS) provides more cosmetic benefits than conventional laparoscopic surgery but presents operational difficulties. To overcome this technical problem, we have developed a locally operated master-slave robot system that provides operability and a visual field similar to conventional laparoscopic surgery. Material and methods: A surgeon grasps the master device with the left hand, which is placed above the abdominal wall, and holds a normal instrument with the right hand. A laparoscope, a slave robot, and the right-sided instrument are inserted through one incision. The slave robot is bent in the body cavity and its length, pose, and tip angle are changed by manipulating the master device; thus the surgeon has almost the same operability as with normal laparoscopic surgery. To evaluate our proposed system, we conducted a basic task and an ex vivo experiment. Results: In basic task experiments, the average object-passing task time was 9.50 sec (SILS cross), 22.25 sec (SILS parallel), and 7.23 sec (proposed SILS). The average number of instrument collisions was 3.67 (SILS cross), 14 (SILS parallel), and 0.33 (proposed SILS). In the ex vivo experiment, we confirmed the applicability of our system for single-port laparoscopic cholecystectomy. Conclusion: We demonstrated that our proposed robot system is useful for single-incision laparoscopic surgery.ArticleMINIMALLY INVASIVE THERAPY & ALLIED TECHNOLOGIES. 23(6):326-332 (2014)journal articl

Real-world Effectiveness and Risk Factors for Discontinuation of Ustekinumab in Ulcerative Colitis

Introduction Ustekinumab (UST) has been approved for the treatment of moderate to severe ulcerative colitis (UC). Real-world data showing the effectiveness and safety of UST are necessary to confirm the results of clinical trials for applicability in daily clinical practice. Although some studies have reported real-world evidence of UST, only few studies have confirmed its effectiveness in the real world. The aim of this study was to assess the short- and long-term effectiveness, durability, safety, and risk factors for discontinuation of UST in UC in clinical practice. Methods This was a retrospective, single-center, observational study. From March 2020 to January 2023, all consecutive patients with active UC who were treated with UST at Nagoya University Hospital were included. The primary outcome was the clinical remission rate at weeks 2–8 and weeks 24–48. The secondary outcomes included clinical response, persistence of UST therapy, endoscopic changes during follow-up, risk factors for UST discontinuation, and occurrence of any adverse events. The clinical effectiveness was evaluated using the Lichtiger score. Results A total of 31 patients were included in this study. The clinical remission rates were 9.7%, 29.0%, 54.8%, and 64.5% at weeks 2, 8, 24, and 48, respectively. Twelve (38.7%) patients discontinued UST during the follow-up period. The probability of continuing UST was 93.5%, 80.6%, 77%, and 70% at weeks 2, 8, 24, and 48, respectively. The major reason for discontinuation of UST was primary failure (75.0%). A high baseline C-reactive protein (CRP) level was a significant risk factor for the discontinuation of UST. No adverse events were observed in this study. Discussion/Conclusion UST is effective for patients with UC. High CRP levels were identified as a risk factor for UST discontinuation. The findings of this study would help clinicians to select appropriate treatment options for patients with UC by identifying the risk factors for treatment discontinuation

Integrated Molecular Profiling of Human Gastric Cancer Identifies DDR2 as a Potential Regulator of Peritoneal Dissemination

Peritoneal dissemination is the most frequent, incurable metastasis occurring in patients with advanced gastric cancer (GC). However, molecular mechanisms driving peritoneal dissemination still remain poorly understood. Here, we aimed to provide novel insights into the molecular mechanisms that drive the peritoneal dissemination of GC. We performed combined expression analysis with in vivo-selected metastatic cell lines and samples from 200 GC patients to identify driver genes of peritoneal dissemination. The driver-gene functions associated with GC dissemination were examined using a mouse xenograft model. We identified a peritoneal dissemination-associated expression signature, whose profile correlated with those of genes related to development, focal adhesion, and the extracellular matrix. Among the genes comprising the expression signature, we identified that discoidin-domain receptor 2 (DDR2) as a potential regulator of peritoneal dissemination. The DDR2 was upregulated by the loss of DNA methylation and that DDR2 knockdown reduced peritoneal metastasis in a xenograft model. Dasatinib, an inhibitor of the DDR2 signaling pathway, effectively suppressed peritoneal dissemination. DDR2 was identified as a driver gene for GC dissemination from the combined expression signature and can potentially serve as a novel therapeutic target for inhibiting GC peritoneal dissemination

Correction: Integrated Multiregional Analysis Proposing a New Model of Colorectal Cancer Evolution.

[This corrects the article DOI: 10.1371/journal.pgen.1005778.]

Integrated Multiregional Analysis Proposing a New Model of Colorectal Cancer Evolution.

Understanding intratumor heterogeneity is clinically important because it could cause therapeutic failure by fostering evolutionary adaptation. To this end, we profiled the genome and epigenome in multiple regions within each of nine colorectal tumors. Extensive intertumor heterogeneity is observed, from which we inferred the evolutionary history of the tumors. First, clonally shared alterations appeared, in which C>T transitions at CpG site and CpG island hypermethylation were relatively enriched. Correlation between mutation counts and patients' ages suggests that the early-acquired alterations resulted from aging. In the late phase, a parental clone was branched into numerous subclones. Known driver alterations were observed frequently in the early-acquired alterations, but rarely in the late-acquired alterations. Consistently, our computational simulation of the branching evolution suggests that extensive intratumor heterogeneity could be generated by neutral evolution. Collectively, we propose a new model of colorectal cancer evolution, which is useful for understanding and confronting this heterogeneous disease