Initial 12 Cases of Robot-Assisted Gastrectomy for Gastric Cancer Using the Hinotori Surgical Robot System: Tips for the Efficient Introduction of a New Surgical Robot.

Introduction: The use of robotic platform for gastrectomy for gastric cancer is rapidly increasing. This study aimed to describe the perioperative outcomes of 12 patients who underwent robotic gastrectomy for gastric cancer using the hinotori™ surgical robot system (hinotori), a novel robot-assisted surgical platform, and compare the outcomes with the existing system, the da Vinci® Surgical System (DVSS). Methods: This study included 12 consecutive patients with gastric cancer who underwent robotic gastrectomy for gastric cancer using the hinotori between March 2023 and September 2023 at our institution. The comprehensive perioperative outcomes of these patients were retrospectively analyzed and compared to 11 patients who underwent robotic gastrectomy using the DVSS during the same period. Results: The median age and body mass index were 71 years (range: 56-86) and 22.7 kg/m2 (range: 16.1-26.7). Distal and total gastrectomy were performed in 8 and 4 patients, respectively. The median console time and operation times were 187 (range: 112-270) and 252 minutes (range: 173-339), respectively. The median blood loss was 3 mL (range: 2-5). No intra- or postoperative complications were observed. There were no significant differences in perioperative outcomes between the hinotori and the DVSS. Conclusions: Robotic gastrectomy for gastric cancer using the hinotori is a feasible procedure and achieved perioperative outcomes similar to that using the DVSS. Clinical Trial Registration number: 114167-1.

Efficacy of the traction method for gastric endoscopic submucosal dissection: a randomized controlled trial (with videos).

BACKGROUND AND AIMS: To overcome the technical difficulties associated with gastric endoscopic submucosal dissection (ESD), a novel traction device that can alter the direction of traction was developed. This study compared the efficacy and safety of conventional ESD versus those of traction-assisted gastric ESD. METHODS: Patients with a single gastric epithelial neoplasm were randomized to receive conventional (n = 75) or traction-assisted (n = 73) gastric ESD. The primary outcome was ESD procedure time. RESULTS: There were no differences between the conventional and traction-assisted groups with respect to treatment results or adverse events. The mean procedure time was similar for both groups (78.9 vs 88.3 minutes, respectively; P = .3); however, times for the traction device tended to be shorter for lesions in the lesser curvature of the upper or middle stomach (84.6 vs 123.2 minutes; P = .057). CONCLUSIONS: Traction-assisted ESD for lesions in the lesser curvature of the upper or middle stomach were shorter, thereby reducing the procedure time of conventional ESD. (Clinical trial registration: University Hospital Medial Information Network Clinical Trials Registry, identifier 000044450.).

Disruption of Circadian Sleep/Wake Rhythms in Infants May Herald Future Development of Autism Spectrum Disorder.

We investigated whether the abnormal rhythms in infants are related to the future development of autism spectrum disorder (ASD), using a questionnaire from September to October 2016. The parents of 160 children with ASD (male, n = 123; female, n = 37) were recruited from two hospitals in K and H cities, and as a control group, 145 children (male, n = 75; female, n = 70) were recruited from four nursery schools in T city. The associations between ASD and bedtime and waking time on weekdays and weekends in infancy (<1 years of age), at 1-3 years, and at 3-5 years of ages were studied using a multivariable logistic regression analysis. In particular, at <3 years of age, the following factors were associated with an increased prevalence of ASD in the future: (1) short sleep periods (<8 h); (2) taking a long time to fall asleep (>60 min); (3) sleep beginning after 22:00; (4) a wake-up time after 08:00; and (5) frequent (>3 times) and long-term awakening periods (>60 min). The misalignment and/or shift of the circadian rhythm in infants may be one of the precursors and/or risk factors for the future development of ASD.

Impact of Arteriosclerosis on Reconstruction-related Complications After Esophagectomy and Usefulness of Tailor-made Reconstruction Technique.

BACKGROUND/AIM: Anastomotic leakage is one of the most common and serious postoperative complications following esophagectomy. This study analyzed the effect of risk factors, such as the degree of arteriosclerosis, comorbidities, and patient characteristics on the incidence of reconstruction-related complications including anastomotic leakage. Furthermore, the usefulness of tailor-made reconstruction methods was clarified using wide gastric conduit. PATIENTS AND METHODS: Patients who underwent esophagectomy with a gastric conduit for esophageal cancer between 2011 and 2018 were enrolled. In the initial group that underwent esophagectomy between August 2011 and February 2016, gastrointestinal reconstruction was performed using a narrow gastric conduit. In the latter group, reconstruction using subtotal gastric conduit was selected for high-risk patients between March 2016 and March 2018. Postoperative complications including reconstruction-related complications were assessed. RESULTS: The occurrence of anastomotic leakage was significantly associated with the patient's risk in the initial group. The rates of anastomotic leakage and reconstruction-related complications were significantly lower in the latter group than in the initial group (3.2% vs. 23.0%, p=0.001; 27.0% vs. 44.3%, p=0.044). The incidence of all complications was significantly lower in the latter group than in the initial group (28.6% vs. 59.0%, p=0.001). The change in bodyweight loss one year after the operation was significantly lower in the latter group than in the initial group (p=0.042). CONCLUSION: Tailor-made reconstruction using wide gastric conduit for high-risk cases of esophageal cancer could reduce the occurrence of anastomotic leakage and promote a better quality of life after surgery.

[Three Cases of Preoperative Chemotherapy(FOLFOXIRI plus Bevacizumab)for Locally Advanced Colorectal Cancer with Urinary Bladder Invasion].

Radical cystectomy for locally advanced colorectal cancer with urinary bladder invasion significantly reduces the quality of life in exchange for a cure. We performed preoperative chemotherapy with FOLFOXIRI plus bevacizumab for 3 patients with locally advanced colorectal cancer with urinary bladder invasion to avoid radical cystectomy and to achieve local control for urinary bladder preservation. Grade 3 neutropenia was observed in 2 patients as an adverse reaction to the preoperative chemotherapy, but all 3 patients showed good tumor regression. All 3 patients underwent laparoscopic high anterior rectal resection and partial cystectomy, and all were able to undergo R0 resections with urinary bladder preservation. One patient had anastomotic leakage as a postoperative complication. One patient had local recurrence in the urinary bladder, and 2 had recurrence with peritoneal dissemination during their postoperative courses. Preoperative chemotherapy(FOLFOXIRI plus bevacizumab)for locally advanced colorectal cancer with urinary bladder invasion is considered to be a useful treatment option because of its potential for tumor shrinkage and bladder preservation.

Chemoprevention of esophageal adenocarcinoma in a rat surgical model by a cysteinyl leukotriene receptor­1 antagonist.

Reflux of gastroduodenal contents into the esophagus leads to the development of esophagitis and inflammation-associated pathologies, such as Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). The role of the lipoxygenase (LOX) pathway in carcinogenesis has been recently reported; however, its involvement in esophageal carcinogenesis remains unclear. To address this, the present study investigated the potential of pranlukast, a cysteinyl leukotriene receptor-1 antagonist, to suppress the progression of BE and EAC in a rat duodenogastroesophageal reflux (DGER) model. Male Wistar rats that underwent DGER were divided into two groups. One group was fed commercial chow (control group), and the other was fed experimental chow containing pranlukast (pranlukast group). The rats were sacrificed at 10, 20, 30 and 40 weeks after surgery, and their esophagi were examined. Expression levels of 5-LOX, CD68, IL-8, VEGF and Ki-67 were investigated using immunohistochemistry, and apoptosis was analyzed using the TUNEL method. In the pranlukast group, esophagitis was milder, and the incidence of BE and EAC was significantly lower (P<0.05) compared with that in the control group at 40 weeks after surgery. The number of cells positive for IL-8 and VEGF were significantly lower in the pranlukast group compared with the control group. Proliferative activity was also lower in the pranlukast group compared with the control group (P<0.05). Pranlukast treatment increased apoptosis (P<0.05). Overall, Pranlukast suppressed esophageal carcinogenesis in a rat DGER model, decreasing inflammatory cytokines such as IL-8 and VEGF.

Thoracoscopic endoscopic cooperative surgery for gastric tube cancer after esophagectomy: a case report.

The incidence of gastric tube cancer (GTC) is increasing due to the improved prognosis of patients after esophagectomy for esophageal cancer. Total resection of the gastric tube is expected to be curative for patients with GTC. However, several studies have reported that this procedure is associated with high mortality and morbidity rates. We here present a case of GTC without lymph node metastasis in a patient who underwent partial resection of a gastric tube via thoracoscopic-endoscopic cooperative surgery. No postoperative complications or recurrence was observed. This procedure is a favorable and minimally invasive procedure for GTC without lymph node metastasis.

Randomized Study of Tenapanor Added to Phosphate Binders for Patients With Refractory Hyperphosphatemia.

Introduction: Serum phosphorus management is important for patients with chronic kidney disease on dialysis to reduce the risk of hyperparathyroidism and ectopic vascular calcification. Phosphate binders (PBs) control serum phosphorus levels; however, some patients do not achieve adequate control with existing PBs. The similar mechanisms of action of each PB may limit their ability to lower serum phosphorus levels. Therefore, drugs with novel mechanisms of action that can be added to existing PBs to further lower serum phosphorus levels are desired. Tenapanor, a novel selective inhibitor of intestinal sodium/hydrogen exchanger 3 transporters, decreases passive phosphate absorption in the intestine, thereby decreasing serum phosphorus levels. Methods: This study evaluated the efficacy and safety of tenapanor treatment with up-titration when added to PBs among Japanese hemodialysis patients with hyperphosphatemia poorly controlled by PBs alone. In total, 169 patients taking PBs whose serum phosphorus level was ≥6.1 and <10.0 mg/dl initiated the 8-week treatment (placebo + PB, n = 85; tenapanor + PB, n = 84). Results: The least squares mean change from baseline to week 8 in serum phosphorus level was -0.24 and -2.00 mg/dl in the placebo and tenapanor groups, respectively, with a statistically significant difference between groups (-1.76 mg/dl; P < 0.0001). Diarrhea as a treatment-emergent adverse event (TEAE) occurred in 14.1% and 63.1% of patients in the placebo and tenapanor groups, respectively. All diarrhea events were mild or moderate. Conclusion: Tenapanor added to PBs improved serum phosphorus levels that could not previously be controlled by PBs alone, and no new safety concerns were raised.

Comparison of the Oral Calcimimetics Evocalcet and Cinacalcet in East Asian Patients on Hemodialysis with Secondary Hyperparathyroidism.

Introduction: Evocalcet is an oral calcimimetic agent with proven efficacy and safety in treating secondary hyperparathyroidism (SHPT) in Japanese patients on dialysis. Methods: This randomized, double-blind, intrapatient dose-adjustment, parallel-group, international multicenter study compared the efficacy and safety of evocalcet versus cinacalcet for 52 weeks in East Asian hemodialysis patients with SHPT. Results: In total, 203 and 200 patients were randomized to receive evocalcet or cinacalcet, respectively (overall, 70.1% had baseline intact parathyroid hormone (PTH) levels ≥500 pg/ml, with no between-group difference). Mean percentage changes in intact PTH levels from baseline were -34.7% and -30.2% in the evocalcet and cinacalcet groups at 52 weeks (between-group difference -4.4%, 95% confidence interval [CI] -13.1%, 4.3%, below the predefined 15% noninferiority margin). Overall, 67.3% and 58.7% of patients in the evocalcet and cinacalcet groups, respectively, achieved ≥30% decrease in intact PTH levels from baseline (between-group difference 8.6%; 95% CI -1.8%, 19.1%). No major safety concerns were observed. Gastrointestinal adverse events (AEs) were significantly less frequent with evocalcet compared with cinacalcet (33.5% vs. 50.5%, P = 0.001), whereas the incidence of hypocalcemia did not differ. Conclusion: Evocalcet might be a better alternative to cinacalcet for East Asian patients on hemodialysis with SHPT.

Impact of preoperative docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy on degree of malignant esophageal stenosis.

BACKGROUND: Malignant esophageal stenosis is a common and severe complication of advanced esophageal cancer that can be a serious problem in the continuation of chemotherapy and other anticancer treatments. The impact of chemotherapy regimens on the degree of improvement in esophageal stenosis is unknown. In this study, we focused on the impacts of chemotherapy on the direct anticancer effects, and in the improvement of malignant stenosis. METHODS: Patients who underwent radical esophagectomy after chemotherapy, either adjuvant 5-fluorouracil and cisplatin (FP) or docetaxel, cisplatin, and 5-fluorouracil (DCF) regimen, were included. We assessed the length of the cancerous stenosis, the width of the narrowest segment, and the size of the intraluminal area in the stenotic segment by fluoroscopy, and compared the differences before and after chemotherapy. In addition, we evaluated the dysphagia score (Mellow-Pinkas scoring system) as the evaluation of patients' symptoms. The antitumor effects of chemotherapy were also investigated. RESULTS: A total of 81 patients were enrolled: 50 were treated with FP, and 31 were treated with DCF. The expansion rate in the length of the narrowest part was significantly increased in the DCF group compared with the FP group. Furthermore, the stenosis index (intraluminal stenotic area/stenotic length) was significantly increased in the DCF group compared with the FP group (112% vs 96%, P = 0.038). Dysphagia score after chemotherapy significantly improved in the DCF group compared to the FP group (P = 0.007). The response rates were 60% in the FP group and 67.7% in the DCF group. Effective histopathological response (improvement to grade 2 or 3) was 24% in the FP group and 38.8% in the DCF group. CONCLUSION: DCF therapy is more effective than FP treatment in the improvement of malignant esophageal stenosis.

Analysis of factors associated with operative difficulty in thoracoscopic esophageal cancer surgery in the left-decubitus position: a single-center retrospective study.

BACKGROUND: The degree of difficulty in the overall procedure and forceps handling encountered by surgeons is greatly influenced by the positional relationship of intrathoracic organs in minimally invasive esophagectomy. This study aimed to identify the anatomical factors associated with the difficulty of minimally invasive esophagectomy assessed by intraoperative injuries and postoperative outcomes. METHODS: Minimally invasive esophagectomy in the left-decubitus position was performed in 258 patients. We defined α (mm) as the anteroposterior distance between the front of the vertebral body and aorta, ß (mm) as the distance between the center of the vertebral body and center of the aorta, and γ (degree) as the angle formed at surgeon's right-hand port site by insertion of lines from the front of aorta and from the front of vertebrae in the computed tomography slice at the operator's right-hand forceps hole level. We retrospectively analyzed the correlations among clinico-anatomical factors, surgeon- or assistant-caused intraoperative organ injuries, and postoperative complications. RESULTS: Intraoperative injuries significantly correlated with shorter α (0.2 vs. 3.9), longer ß (33.0 vs. 30.5), smaller γ (3.0 vs. 4.3), R1 resection (18.5% vs. 8.3%), and the presence of intrathoracic adhesion (46% vs. 26%) compared with the non-injured group. Division of the median values into two groups showed that shorter α and smaller γ were significantly associated with organ injury. Longer ß was significantly associated with postoperative tachycardia onset, respiratory complications, and mediastinal recurrence. Furthermore, the occurrence of intraoperative injuries was significantly associated with the onset of postoperative pulmonary complications. CONCLUSIONS: Intrathoracic anatomical features greatly affected the procedural difficulty of minimally invasive esophagectomy, suggesting that preoperative computed tomography simulation and appropriate port settings may improve surgical outcomes.

Successful treatment of nonocclusive mesenteric ischemia in a reconstructed jejunum after esophagectomy and remnant gastric tube resection: a case report.

BACKGROUND: Nonocclusive mesenteric ischemia (NOMI), an ischemic bowel disease without a disruption of the mesenteric blood flow or strangulation of the mesentery or intestine, may cause a lethal clinical course. We report a very rare case of jejunal necrosis caused by NOMI in the pedicled mesentery of the reconstructed jejunum after remnant gastric tube resection for heterochronous gastric tube cancer after esophagectomy. CASE PRESENTATION: An 80-year-old man visited our department with chief complaints of fever and appetite loss after 4 months from gastric tube resection and digestive reconstruction with pedicled jejunum. Contrast-enhanced computed tomography (CT) revealed impaired blood flow without torsion of the mesentery, severe wall thickness, and micro-penetration in the reconstructed jejunum and combined pyothorax in the right thoracic cavity. Esophagogastroduodenoscopy demonstrated extensive mucosal necrosis confined to the jejunum, which was elevated in the thoracic cavity. The jejunal necrosis due to NOMI occurring in the reconstructed jejunum was suspected, and lifesaving small bowel resection with right thoracotomy was considered necessary. However, radical operation with right thoracotomy was considered to be excessively invasive and not valid due to the patient's poor physical status, advanced age, and presence of left adrenal metastasis from the remnant gastric cancer. Therefore, we selected the conservative treatment with fasting, transnasal drainage, and administration of antibiotics due to the patient's intention. CT-guided right thoracic drainage for the intrathoracic abscess was needed 10 days after starting treatment and the inflammatory response rapidly improved. Follow-up CT and esophagogastroduodenoscopy revealed the improvement in the ischemic changes in jejunal mucosa without perforation. Intake was initiated at 20 days after symptom onset, and the patient was discharged at 40 hospital days without any complications and sequelae. CONCLUSIONS: To the best of our knowledge, this is the first case of NOMI occurring in the reconstructed jejunum after remnant gastric tube resection that was successfully treated with a conservative treatment. For NOMI, it is important to make appropriate diagnosis based on imaging findings and perform proper assessment of the patient's condition. Conservative treatments may be also useful depending on the patient's condition.

Multicenter randomized control study of the efficacy of SO clip in colorectal endoscopic submucosal dissection (ESD). (SO clip study in colorectal ESD): Randomized controlled trial.

INTRODUCTION: Endoscopic submucosal dissection (ESD) allows the en bloc resection of colorectal epithelial tumors regardless of size. Although ESD is minimally invasive and yields favorable outcomes, it is technically difficult and requires a long procedure time. In addition, colorectal ESD is associated with a particularly high risk of complications, due to the thin bowel wall, bowel flexion, and peristalsis.Direct visualization of the submucosal layer by traction of the lesion after mucosal dissection would make ESD performance easier. S-O clips traction lesions toward the lumen, facilitating direct visualization of the submucosal layer, resulting in efficient dissection due to the traction effect and adequate dissection depth. Use of this traction device can contribute to shortening the procedure time and reducing the risk of complications. This multicenter randomized controlled trial will evaluate the usefulness of the S-O clip in colorectal ESD and assess the procedure time and frequency of complications associated with the procedure. METHODS/DESIGN: This multicenter, randomized control trial will enroll 200 patients at 4 hospitals in Japan undergoing ESD for colorectal epithelial tumors. Patients who meet the inclusion and exclusion criteria will be randomized to undergo ESD using S-O clips or conventional ESD. Patients will be randomized by a computer-generated random sequence with stratification by operator experience (trainee or expert), tumor location (colon/rectum), and institution. The primary endpoint will be ESD procedure time, defined as the time from the start of the local injection into the submucosal layer to the end of dissection. Other outcomes will include the rates of procedural complications, en bloc resection and cure. DISCUSSION: ESD using the S-O clip is expected to shorten procedure time, reduce the incidence of adverse events, and standardize the procedure. This study may resolve clinical questions about whether ESD using the S-O clip traction device is more effective and safer than conventional ESD.

Endoscopic N-butyl-2-cyanoacrylate and ethanolamine oleate injection is equivalent to balloon-occluded retrograde transvenous obliteration for preventing gastric variceal bleeding.

OBJECTIVES: Endoscopic injection sclerotherapy (EIS) is effective for temporary hemostasis, but EIS and balloon-occluded retrograde transvenous obliteration (BRTO) have been reported as effective for secondary prophylaxis of gastric varices (GV) bleeding. This study retrospectively compared EIS and BRTO in patients with GV in terms of the efficacy for secondary prevention of GV bleeding and effects on liver function. METHODS: From our database of patients with GV who underwent EIS or BRTO between February 2011 and April 2020, a total of 42 patients with GV were retrospectively enrolled. The primary endpoint was the bleeding rate from GV, which was compared between EIS and BRTO groups. Secondary endpoints were liver function after treatment and rebleeding rate from EV, compared between EIS and BRTO groups. Rebleeding rates from GV and EV and liver function after treatment were also compared between EIS-ethanolamine oleate (EO)/histoacryl (HA) and EIS-HA groups. RESULTS: Technical success was achieved for all EIS cases, but two cases were unsuccessful in the BRTO group and underwent additional EIS. No significant differences in bleeding rates or endoscopic findings for GV improvement were seen between EIS and BRTO groups. Liver function also showed no significant difference in the amount of change after treatment between groups. CONCLUSION: EIS therapy appears effective for GV in terms of preventing GV rebleeding and effects on liver function after treatment. EIS appears to represent an effective treatment for GV.

Robot-assisted distal gastrectomy for duodenal gastrointestinal stromal tumors adhering to the pancreas: a case report.

Duodenal gastrointestinal stromal tumors (D-GISTs) are uncommon and account for 3-5% of all GISTs. Currently, no established surgical strategy for D-GISTs exists, which mostly depends on tumor size, relation to the ampulla and invasion of the adjacent organ. We report a case of large D-GIST resected by robotic distal gastrectomy. A 62-year-old woman was diagnosed with a 5-cm D-GIST located at posterior wall of the duodenal bulb. Computed tomography findings indicated possible tumor invasion of the pancreas head. Robot-assisted distal gastrectomy was firstly planned and pancreatoduodenectomy was also considered when the tumor was invading to the pancreas. Although tumor was tightly adherent to the pancreas, it could be dissected from the pancreatic head without capsule damage and resected by robotic distal gastrectomy with no postoperative complication. The large D-GIST tightly adherent to the pancreas could be resected by efficiency of the robotic surgery.

Successful second conversion surgery after trastuzumab deruxtecan for recurrent HER2-positive gastric cancer.

A 65-year-old woman with HER2-positive gastric cancer with multiple liver metastases underwent first conversion surgery of gastrectomy with D2 lymph nodes dissection and three liver metastases after combination therapy with capecitabine, cisplatin, and trastuzumab. Two years later, she experienced multiple liver metastases that were refractory to combination therapy with paclitaxel albumin-bound nanoparticles and ramucirumab. She participated in the DESTINY-Gastric01 trial and received tri-weekly trastuzumab deruxtecan as third-line treatment for 26 cycles. The recurrent lesions markedly shrank, and this effect continued for 19 months. We then performed partial hepatectomy for the one remaining lesion. No adjuvant chemotherapy was given, and she remains alive without recurrence 18 months after the second conversion surgery. Trastuzumab deruxtecan may generate a notable tumor response and subsequent conversion surgery could be a treatment option for HER2-positive stage IV gastric cancer.

Suppression of galectin-4 attenuates peritoneal metastasis of poorly differentiated gastric cancer cells.

BACKGROUND: Peritoneal dissemination, most often seen in metastatic and/or recurrent gastric cancer, is an inoperable condition that lacks effective treatment. The use of molecular targeted drugs is also limited; therefore, identifying novel therapeutic targets and improving our understanding of this metastatic cancer are an urgent requirement. In this study, we focused on galectin-4, which is specifically expressed in poorly differentiated cells with high potential for peritoneal dissemination. METHODS: We knocked out the galectin-4 gene in NUGC4 cells using CRISPR/Cas9-mediated genome editing. Proliferation and peritoneal cancer formation in knockout cells were compared with those in wild-type and galectin-4 re-expressing cells. Western blotting and proximity ligation assays were performed to identify associated molecules affected by the expression of galectin-4. The effect of galectin-4 knockdown on cell proliferation and peritoneal metastasis was studied using a specific siRNA. Expression of galectin-4 in peritoneal metastatic tumors from 10 patients with gastric cancer was examined by immunohistochemistry. RESULTS: Suppression of galectin-4 expression reduced proliferation and peritoneal metastasis of malignant gastric cancer cells. Galectin-4 knockout and knockdown reduced the expression of activated c-MET and CD44. Galectin-4 was found to interact with several proteins on the cell surface, including CD44 and c-MET, via its carbohydrate-binding ability. Immunohistochemistry showed galectin-4 expression in peritoneal metastatic tumor cells in all patients examined. CONCLUSIONS: We clarified the role of galectin-4 in the development of peritoneal dissemination of poorly differentiated gastric cancer cells. Our data highlight the diagnostic and therapeutic potential of galectin-4 in the peritoneal dissemination of gastric cancer.