Hybrid Abdominal Robotic Approach Using the hinotori™ Surgical Robot System with Transanal Total Mesorectal Excision for Rectal Cancer: The First Ever Case Report for Rectal Cancer.

In Japan, the hinotori™ Surgical Robot System obtained pharmaceutical approval for use in colorectal cancer surgery in October 2022. This system has an operating arm with eight axes, adjustable arm base, and flexible three-dimensional viewer, which are expected to be advantageous in colorectal cancer surgery. A 55-year-old man presented to our hospital with melena and was diagnosed with cStage IIA (cT3N0M0) rectal cancer. The patient underwent intersphincteric resection using hinotori™ Surgical Robot System. Appropriate port placement was available for rectal manipulation, lymph node dissection, and arm base angle adjustment. Herein, we report the world's first rectal cancer surgery using the hinotori™ Surgical Robot System with TaTME by two teams.

FADS2 confers SCD1 inhibition resistance to cancer cells by modulating the ER stress response.

Stearoyl-CoA desaturase 1 (SCD1) is an attractive target for cancer therapy. However, the clinical efficacy of SCD1 inhibitor monotherapy is limited. There is thus a need to elucidate the mechanisms of resistance to SCD1 inhibition and develop new therapeutic strategies for combination therapy. In this study, we investigated the molecular mechanisms by which cancer cells acquire resistance to endoplasmic reticulum (ER) stress-dependent cancer cell death induced by SCD1 inhibition. SCD1 inhibitor-sensitive and -resistant cancer cells were treated with SCD1 inhibitors in vitro, and SCD1 inhibitor-sensitive cancer cells accumulated palmitic acid and underwent ER stress response-induced cell death. Conversely, SCD1-resistant cancer cells did not undergo ER stress response-induced cell death because fatty acid desaturase 2 (FADS2) eliminated the accumulation of palmitic acid. Furthermore, genetic depletion using siRNA showed that FADS2 is a key determinant of sensitivity/resistance of cancer cells to SCD1 inhibitor. A549 cells, an SCD1 inhibitor-resistant cancer cell line, underwent ER stress-dependent cancer cell death upon dual inhibition of SCD1 and FADS2. Thus, combination therapy with SCD1 inhibition and FADS2 inhibition is potentially a new cancer therapeutic strategy targeting fatty acid metabolism.

Cylindrical abdominoperineal resection for rectal cancer using the Hugo RAS system: The first ever case report for rectal cancer.

In May 2023, the Hugo RAS system obtained pharmaceutical approval for use in gastroenterological surgery in Japan. It is expected to be particularly effective in rectal cancer surgery, which require the manipulation of the deep pelvic cavity and communication with surgeons operating from the intraperitoneal and anal approaches. A 68-year-old woman presented to our hospital with bloody stools and was diagnosed with cStage I (cT2N0M0) rectal cancer and underwent abdominoperineal resection employing the Hugo RAS system. Two arm carts were placed on the left and right lateral sides with an interleg space, and trocars were placed in a straight line between the right superior iliac spine and umbilicus. Herein, we report the first abdominoperineal resection for rectal cancer using the Hugo RAS system.

A first report of right-hemicolectomy for ascending colon cancer in Japan with the da Vinci SP surgical robot system.

BACKGROUND: The da Vinci SP robotic surgical system received regulatory approval for use in colorectal cancer surgery in Japan in April 2023. Given the advantages of the precision of a robot and the postoperative cosmesis of single-site surgery, the system is expected to be further utilized for minimally invasive surgeries, in addition to the curative and safety-assured laparoscopic technique. CASE PRESENTATION: A 73-year-old man presented at our hospital with positive fecal occult blood. He was diagnosed with cT2N0M0 (Stage I) ascending colon cancer and underwent a right hemicolectomy, which was performed with the da Vinci SP system. The operation was performed safely, and the patient was discharged without complications. Pathology findings showed that complete mesocolic excision was achieved. CONCLUSIONS: Herein, we report the first colorectal cancer surgery performed using the da Vinci SP system in Japan. The use of this robotic surgical system with access forms for right hemicolectomy is safe and oncologically appropriate.

Development of an LC-MS/MS method for the determination of five psychoactive drugs in postmortem urine by optimization of enzymatic hydrolysis of glucuronide conjugates.

PURPOSE: Toxicological analyses of biological samples play important roles in forensic and clinical investigations. Ingested drugs are excreted in urine as conjugates with endogenous substances such as glucuronic acid; hydrolyzing these conjugates improves the determination of target drugs by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this study, we sought to improve the enzymatic hydrolysis of glucuronide conjugates of five psychoactive drugs (11-nor-9-carboxy-Δ9-tetrahydrocannabinol, oxazepam, lorazepam, temazepam, and amitriptyline). METHODS: The efficiency of enzymatic hydrolysis of glucuronide conjugates in urine was optimized by varying temperature, enzyme volume, and reaction time. The hydrolysis was performed directly on extraction columns. This analysis method using LC-MS/MS was applied to forensic autopsy samples after thorough validation. RESULTS: We found that the recombinant ß-glucuronidase B-One® quantitatively hydrolyzed these conjugates within 3 min at room temperature directly on extraction columns. This on-column method saved time and eliminated the loss of valuable samples during transfer to the extraction column. LC-MS/MS-based calibration curves processed with this method showed good linearity, with r2 values exceeding 0.998. The intra- and inter-day accuracies and precisions of the method were 93.0-109.7% and 0.8-8.8%, respectively. The recovery efficiencies were in the range of 56.1-104.5%. Matrix effects were between 78.9 and 126.9%. CONCLUSIONS: We have established an LC-MS/MS method for five psychoactive drugs in urine after enzymatic hydrolysis of glucuronide conjugates directly on extraction columns. The method was successfully applied to forensic autopsy samples. The established method will have broad applications, including forensic and clinical toxicological investigations.

World-first report of low anterior resection for rectal cancer with the hinotori™ Surgical Robot System: a case report.

BACKGROUND: The hinotori™ Surgical Robot System was approved for use in colorectal cancer surgery in Japan in 2022. This robot has advantages, such as an operation arm with eight axes, an adjustable arm base, and a flexible three-dimensional viewer, and is expected to be utilized in rectal cancer surgery. Herein, we report the world's first surgery for rectal cancer using the hinotori™ Surgical Robot System. CASE PRESENTATION: A 71-year-old woman presented to our hospital with bloody stools. A colonoscopy revealed type 2 advanced cancer in the rectum, and a histological examination exposed a well-differentiated adenocarcinoma. Abdominal enhanced computed tomography divulged rectal wall thickening without significant swelling of the lymph nodes or distant metastasis. Pelvic magnetic resonance imaging showed tumor invasion beyond the intrinsic rectal muscle layer. The patient was diagnosed with cStage IIa (cT3N0M0) rectal cancer and underwent low anterior resection using the hinotori™ Surgical Robot System. Based on an adequate simulation, surgery was safely performed with appropriate port placement and arm base-angle adjustment. The operating time was 262 min, with a cockpit time of 134 min. Subsequently, the patient was discharged 10 days postoperatively without complications. The pathological diagnosis was pStage IIA (cT3N0M0) and the circumferential resection margin was 6 mm. CONCLUSIONS: We report the first case of low anterior resection for rectal cancer using the hinotori™ Surgical Robot System, in which a safe and appropriate oncological surgery was performed.

Right hemicolectomy for ascending colon cancer using the hinotori surgical robot system: The first ever case report for colon cancer.

The hinotori Surgical Robot System obtained pharmaceutical approval for use in colorectal cancer surgery in October 2022 in Japan, and its advantages, including its operating arm with eight axes, adjustable arm base, and flexible 3D viewer, are expected to be utilized in colon cancer surgery. A 68-year-old woman presented to our hospital with abdominal pain and was diagnosed with cStageIIa (cT3N0M0) ascending colon cancer and underwent right hemicolectomy using the hinotori Surgical Robot System with the appropriate port placement on the arc around the hepatic flexure, which was available for both ileocecal manipulation and lymph node dissection, and adjustment of the angle of the arm base to further reduce interference. Herein we report the world's first surgery for colorectal cancer using the hinotori Surgical Robot System.

Laparoscopic mesh repair and Toupet fundoplication for parahiatal hernia complicated by sliding hiatal hernia: A case report.

INTRODUCTION: The parahiatal hernia is a rare type of diaphragmatic hernia in adults. Although there have been occasional reports of parahiatal hernias, few have reported simultaneous laparoscopic mesh repair of a parahiatal hernia with a hiatal hernia. This report describes laparoscopic mesh repair and fundoplication for a parahiatal hernia combined with an esophageal hiatal hernia. PRESENTATION OF CASE: A 39-year-old woman presented with left-side postprandial abdominal pain. Esophagogastroduodenoscopy revealed a parahiatal hernia and sliding hiatal hernia. Computed tomography (CT) showed that the stomach had prolapsed into the thorax from the outside of the left diaphragm. The preoperative diagnosis was parahiatal hernia with a hernial sac complicated by sliding hiatal hernia. Laparoscopic mesh repair was planned. The stomach had prolapsed on the left side of the esophagus and was extruded. The diagnosis of a parahiatal hernia with a hernial sac complicated by a sliding hiatal hernia was confirmed. The esophageal hiatal hernia was repaired using two non-absorbable sutures. The congenital defect was further reinforced with mesh fixed to the orifice of the adjacent parahiatal hernia. We performed Toupet fundoplication to treat gastroesophageal reflux disease and sutured the right diaphragmatic crus and stomach to prevent migration. The patient was discharged home on postoperative day 5. CONCLUSION: We encountered a patient with a parahiatal hernia complicated by a sliding hiatal hernia. The parahiatal hernia can be diagnosed by CT imaging. Preoperative diagnostic imaging can lead to appropriate treatment.

Novel extraction method using an ISOLUTE PLD+ protein and phospholipid removal column for liquid chromatography-tandem mass spectrometry analysis of 20 psychoactive drugs in postmortem whole blood samples.

A novel sample extraction method using an ISOLUTE PLD+ protein and phospholipid removal column was developed for simultaneous quantification of 20 psychoactive drugs, including antidepressants, antipsychotics, sedative-hypnotics, and amphetamines, in postmortem whole blood samples by liquid chromatography-tandem mass spectrometry. The method showed improvement in extract cleanliness compared with traditional protein precipitation and the QuEChERS extraction method. The method was validated for all analytes; the calibration curves showed good linearity, with r2 values exceeding 0.991. The intra- and interday accuracies and precisions were 87.6-117.5% and 1.0-18.6%, respectively. The recovery efficiencies were in the range of 64.6-96.8%. Matrix effects were observed in the range of 82.6-116.0%. All analytes were stable under different storage conditions. This method was successfully applied in postmortem forensic sample analysis to quantify psychoactive drugs. The method described in the current study will be useful for forensic toxicological investigations.

Application of Lithium Assay kit LS for quantification of lithium in whole blood and urine.

A commercially available kit for the quantitation of lithium, the Lithium Assay kit LS, was originally developed to measure lithium in serum or plasma using a conventional microplate reader. We investigated whether use of the kit could be extended to quantify lithium in whole blood and urine samples collected at autopsy. The calibration curve for whole blood showed good linearity ranging from 0.5 to 20 µg/mL with a coefficient of determination of 0.998 when samples were pretreated with methanol followed by acetonitrile. Moreover, for urine, we obtained excellent linearity with a coefficient of determination of 0.999 without any pretreatment. The accuracies and precisions were 106.3-174.7% and 1.9-18.1% for whole blood and 83.3-118.8% and 5.7-33.8% for urine. The values in the lower concentration range (0.5-1 µg/mL) were not satisfactory, whereas those in the higher range (2-20 µg/mL) were acceptable. The Lithium Assay kit LS was successfully applied to the measurement of lithium in whole blood and urine samples collected at autopsies. This method appears to be useful for forensic toxicological investigations because of its simplicity and speed.

Cardioprotection via Metabolism for Rat Heart Preservation Using the High-Pressure Gaseous Mixture of Carbon Monoxide and Oxygen.

The high-pressure gas (HPG) method with carbon monoxide (CO) and oxygen (O2) mixture maintains the preserved rat heart function. The metabolites of rat hearts preserved using the HPG method (HPG group) and cold storage (CS) method (CS group) by immersion in a stock solution for 24 h were assessed to confirm CO and O2 effects. Lactic acid was significantly lower and citric acid was significantly higher in the HPG group than in the CS group. Moreover, adenosine triphosphate (ATP) levels as well as some pentose phosphate pathway (PPP) metabolites and reduced nicotinamide adenine dinucleotide phosphate (NADPH) were significantly higher in the HPG group than in the CS group. Additionally, reduced glutathione (GSH), which protects cells from oxidative stress, was also significantly higher in the HPG group than in the CS group. These results indicated that each gas, CO and O2, induced the shift from anaerobic to aerobic metabolism, maintaining the energy of ischemic preserved organs, shifting the glucose utilization from glycolysis toward PPP, and reducing oxidative stress. Both CO and O2 in the HPG method have important effects on the ATP supply and decrease oxidative stress for preventing ischemic injury. The HPG method may be useful for clinical application.

Incarcerated femoral hernia treated with elective totally extraperitoneal repair: a case report.

Incarcerated groin hernia is a common surgical emergency. However, reports of incarcerated femoral hernia treated with elective totally extraperitoneal repair are extremely rare. A 62-year-old woman visited our hospital with lower abdominal pain and bulging from a right groin lesion. The patient was diagnosed as having right incarcerated femoral hernia containing greater omentum by computed tomography. As there were no clear findings of intestinal obstruction and peritonitis, elective surgery was performed. Intraoperatively, the hernia sac had herniated into the right femoral canal. We could release the hernia sac using laparoscopic forceps. After reduction of the hernia sac, polypropylene mesh was placed in the preperitoneal space and fixed to Cooper's ligament. The patient's postoperative course was uneventful, and she was discharged 3 days after surgery. We consider elective totally extraperitoneal repair for incarcerated femoral hernia to be an effective procedure for selected patients who have been diagnosed accurately.

Clostridium butyricum Modulates the Microbiome to Protect Intestinal Barrier Function in Mice with Antibiotic-Induced Dysbiosis.

Clostridium butyricum MIYAIRI 588 (CBM 588) is a probiotic bacterium that has previously been used to prevent antibiotic-associated diarrhea. However, the underlying mechanism by which CBM 588 protects the gut epithelial barrier remains unclear. Here, we show that CBM 588 increased the abundance of Bifidobacterium, Lactobacillus, and Lactococcus species in the gut microbiome and also enhanced the intestinal barrier function of mice with antibiotic-induced dysbiosis. Additionally, CBM 588 significantly promoted the expansion of IL-17A-producing γδT cells and IL-17A-producing CD4 cells in the colonic lamina propria (cLP), which was closely associated with changes in the intestinal microbial composition. Additionally, CBM 588 plays an important role in controlling antibiotic-induced gut inflammation through upregulation of anti-inflammatory lipid metabolites such as palmitoleic acid, 15d-prostaglandin J2, and protectin D1. This study reveals a previously unrecognized mechanism of CBM 588 and provides new insights into gut epithelial barrier protection with probiotics under conditions of antibiotic-induced dysbiosis.

The impact of dementia on surgical outcomes of laparoscopic cholecystectomy for symptomatic cholelithiasis and acute cholecystitis: A retrospective study.

INTRODUCTION: The aim of this study was to clarify the impact of dementia on surgical outcomes of laparoscopic cholecystectomy for symptomatic cholelithiasis and acute cholecystitis. METHODS: We reviewed medical data of 96 patients who underwent laparoscopic cholecystectomy for symptomatic cholecystitis and acute cholecystitis. The patients were divided into the dementia group (n = 18) and non-dementia group (n = 78). Clinical features of the patients and surgical outcomes were compared between the two groups. RESULTS: Mean age and rates of The American Society of Anesthesiologists Physical Status classification score > 2 in the dementia group were significantly higher than those of the non-dementia group (P < .001, P = .008, respectively). Incidences of acute cholecystitis and the rate of percutaneous transhepatic gallbladder drainage in the dementia group were significantly higher than those of the non-dementia group (P = .009, P = .01, respectively). The rates of conversion to laparotomy and non-surgical complications in the dementia group were higher than those in the non-dementia group (P = .02, P = .03, respectively). Postoperative hospital stay in the dementia group was significantly longer than that in the non-dementia group (15.2 ± 9.3 vs 8.2 ± 3.2 days, P = .009). Subgroup analysis of patients with acute cholecystitis showed postoperative hospital stay in the dementia group to be significantly longer than that in the non-dementia group (18.7 ± 10.7 vs 10.3 ± 4.2 days, P = .03). CONCLUSION: Patients with dementia who underwent laparoscopic cholecystectomy have a high incidence of acute cholecystitis and a high rate of percutaneous transhepatic gallbladder drainage, which may result in increased rates of conversion to laparotomy and prolong the postoperative hospital stay.

Effect of Residual Stress on Thermal Deformation Behavior.

This paper discusses a non-destructive measurement technique of residual stress through optical visualization. The least amount of deformation possible is applied to steel plates by heating the specimens +10 °C from room temperature for initial calibration, and the thermal expansion behavior is visualized with an electronic speckle pattern interferometer sensitive to two dimensional in-plane displacement. Displacement distribution with the thermal deformation and coefficient of thermal expansion are obtained through interferometric fringe analysis. The results suggest the change in the thermal deformation behavior is affected by the external stress initially applied to the steel specimen. Additionally, dissimilar joints of steel and cemented carbide plates are prepared by butt-brazing. The residual stress is estimated based on the stress dependence of thermal expansion coefficient.

Internal hernia beneath the left external iliac artery after robotic-assisted laparoscopic prostatectomy with extended pelvic lymph node dissection: a case report.

BACKGROUND: Formation of an internal hernia beneath a skeletonized pelvic vessel after pelvic lymph node dissection is extremely rare. We report a case of an internal hernia formation beneath the left external iliac artery after a robotic-assisted laparoscopic prostatectomy with extended pelvic lymph node dissection. CASE PRESENTATION: A 72-year-old man visited our hospital complaining of severe lower abdominal pain. On physical examinations, his abdomen was distended and tympanitic with rebound tenderness and muscular defense. Abdominal non-enhanced computed tomography showed a small bowel obstruction with marked ascites. A coronal non-enhanced computed tomography image revealed thickened loops of small bowel with surrounding mesenteric edema in the left lower quadrant. Enhanced computed tomography was not performed because we decided to perform urgent surgery with a diagnosis of strangulated small bowel obstruction based on physical examination and the computed tomography findings. The patient underwent urgent laparotomy at which time bloody ascites was seen in the peritoneal cavity. The ileum, which was approximately 60 cm proximal to the ileocecal junction, formed a closed loop beneath the left external iliac artery. The incarcerated ileum, 120 cm in length, appeared non-viable with a color change of the ileum to black. We therefore resected the strangulated ileum for a length of 120 cm and performed a functional end-to-end anastomosis. The orifice beneath the left external iliac artery was about 4 cm in diameter. We did not close the orifice because of the risk of injuring the left iliac artery. The postoperative course was uneventful, and the patient was discharged from our hospital 10 days after surgery. Presently, the patient is doing well 5 months after surgery without recurrent disease. CONCLUSION: We report an extremely rare case of internal hernia formation beneath the left external iliac artery after a robotic-assisted laparoscopic prostatectomy with extended pelvic lymphadenectomy. Awareness of such complication and early surgical treatment are important when treating patients with this rare occurrence.

A new method for simultaneous quantification of fosphenytoin, phenytoin and its primary metabolite 5-(4-hydroxyphenyl)-5-phenylhydantoin in whole blood by ultra-performance liquid chromatography-tandem mass spectrometry.

A method for simultaneous quantification of fosphenytoin (F-PHT), phenytoin (PHT) and its main metabolite 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH) in whole blood was developed and validated using ultra-performance liquid chromatography-tandem mass spectrometry. Whole blood samples were pretreated by liquid-liquid extraction with acetonitrile and methanol. Chromatographic separation was performed using a CORTECS™ UPLC® C18 (2.1 × 50 mm i.d., particle size 1.6 µm) analytical column, and water containing 10 mM ammonium formate and acetonitrile as the mobile phase. Quantification of the analytes was carried out using mass chromatography with each product ion referenced against phenytoin-d10 as an internal standard. Calibration curves exhibited good linear relationships in a range from 0.005 to 50 µg/ml with correlation coefficients exceeding 0.995. The limits of detection were estimated to be 0.002-0.01 µg/ml. The accuracies and precisions were 96.2-104.3% and 0.7-10.7%, respectively. The recovery efficiencies were in the range of 42.4-59.2%. Matrix effects were observed for PHT and HPPH, with signal suppression ranging from -6.6 to -32.2%. Matrix effect for F-PHT (-5.0 to 8.9%) was less than those for PHT and HPPH. All analytes were stable under different storage conditions. This method was successfully applied for the quantification of F-PHT, PHT and HPPH in rat whole blood samples taken after bolus intravenous administration of F-PHT.

Long-term outcomes of neoadjuvant-synchronous S-1 plus radiotherapy for locally advanced rectal cancer: a multi-institutional prospective phase II study.

OBJECTIVES: This study aimed to evaluate the long-term outcomes of neoadjuvant chemoradiotherapy with S-1 in patients with locally advanced rectal cancer. METHODS: A multi-institutional, prospective, phase II trial was conducted between April 2009 and August 2011. The study enrolled 37 patients with histologically proven rectal carcinoma (T3-4 N0-3 M0) who underwent neoadjuvant chemoradiotherapy with S-1. Total mesorectal excision with D3 lymphadenectomy was performed 4-8 weeks after completion of neoadjuvant chemoradiotherapy with S-1 in 36 patients. We then analyzed late adverse events, overall survival, and disease-free survival. RESULTS: The median patient age was 59 years (range: 32-79 years); there were 24 men and 13 women. Ten patients had Stage II disease, and 27 had Stage III disease. Severe late adverse events occurred in 7 patients (18.9%). The 5-year disease-free survival was 66.7%, and the 5-year overall survival was 74.7%. The median follow-up period was 57 months. Local recurrences developed in 5 patients (13.5%), and distant metastases developed in 8 (21.6%). CONCLUSION: Neoadjuvant-synchronous chemoradiotherapy with S-1 for locally advanced rectal cancer is feasible in terms of adverse events and long-term outcomes. (UMIN Clinical Trial Registry: UMIN000003396).

Simultaneous quantification of batrachotoxin and epibatidine in plasma by ultra-performance liquid chromatography/tandem mass spectrometry.

An ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous quantification of batrachotoxin and epibatidine in plasma. Plasma samples were pretreated by liquid-liquid extraction with acetonitrile and methanol. The toxins were separated on a reversed phase C18-column (2.1mm×50mm, 1.7µm) using a formic acid/acetonitrile gradient elution. Quantification was carried out by mass chromatography with each product ion referenced against midazolam-d4 as an internal standard (IS). The two toxins and the IS were separated within 2min. The calibration curves for the two toxins spiked into human plasma showed good linearities in the range from 2.5 to 250ng/mL. The detection limits were estimated to be 0.5ng/mL for batrachotoxin and 1ng/mL for epibatidine with a signal-to-noise ratio of 3:1. Overall recoveries ranged from 69.6% to 98.2%, and no significant matrix effects were observed. The intra- and interday accuracies were 94.7-102.3%, and the precisions were 1.0-10.3%. This method was successfully applied for the quantification of batrachotoxin and epibatidine in rat plasma samples taken after intraperitoneal administration of the toxins. This is the first report to use UPLC-MS/MS to simultaneously quantify batrachotoxin and epibatidine in plasma samples.

LY6/PLAUR domain containing 3 has a role in the maintenance of colorectal cancer stem-like cells.

Colorectal carcinoma (CRC) is one of the most frequently diagnosed cancers and the leading cause of cancer-related death for both men and women. Recent studies have revealed that a small sub-population of cancer cells, termed cancer stem-like cells (CSCs)/cancer-initiating cells (CICs), are endowed with tumor-initiating ability, self-renewal ability and differentiation ability. CSCs/CICs are resistant to current therapies including chemotherapy and radiotherapy. Thus, CSCs/CICs are responsible for recurrence and metastasis, and eradication of CSCs/CICs is essential to cure cancer. In this study, we isolated CR-CSCs/CICs as sphere-cultured cells and found that a product derived from LY6/PLAUR domain containing 3 (LYPD3) is preferentially expressed in CSCs/CICs. Gene overexpression and gene knockdown experiments revealed that LYPD3 has a role in the maintenance of CR-CSCs/CICs. The findings provide a novel molecular insight into CR-CSCs/CICs.