Prognostic Significance of 18F-FDG PET/CT and Tumor Metabolic Changes in Patients With Pancreatic Ductal Adenocarcinoma.

BACKGROUND/AIM: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is reportedly associated with the malignant potential of cancer. This study aimed to evaluate the association between FDG accumulation and tumor metabolism in pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: A prognostic analysis of data from 131 patients with PDAC who underwent FDG-PET/CT before curative-intent pancreatic surgery was performed. Capillary electrophoresis-mass spectrometry (CE-MS) was used to analyze the metabolome of tumor and non-neoplastic pancreas from 80 patients. These patients were divided into two groups: low SUVmax group (SUVmax <6.09) and high SUVmax group (SUVmax ≥6.09). RESULTS: Carbohydrate antigen 19-9 (CA19-9), maximum standardized uptake value (SUVmax) of PET, N stage, and postoperative chemotherapy were identified as significant prognostic factors by univariate analysis. SUVmax emerged as an independent prognostic factor for overall survival [hazard ratio (HR)=1.88, p<0.05] and disease-free survival (HR=2.01, p<0.05) in multivariate analysis. Metabolic analyses confirmed that 43 metabolites significantly differed depending on the accumulation of SUV in tumors. Metabolites involved in the removal of reactive oxygen species (e.g., hypotaurine, glutathione, Met), treatment resistance (UDP-N-acetylglucosamine), and proliferation (e.g., choline, leucine, isoleucine) were increased in the high SUVmax group. CONCLUSION: FDG accumulation is an important independent prognostic factor reflecting tumor activity associated with metabolic changes in cancer cells.

Identification of organs of origin of macrophages that produce presepsin via neutrophil extracellular trap phagocytosis.

Presepsin (P-SEP) is a specific biomarker for sepsis. Monocytes produce P-SEP by phagocytosing neutrophil extracellular traps (NETs). Herein, we investigated whether M1 macrophages (M1 MΦs) are the primary producers of P-SEP after NET phagocytosis. We co-cultured M1 MΦs and NETs from healthy participants, measured P-SEP levels in the culture medium supernatant, and detected P-SEP using western blotting. When NETs were co-cultured with M1 MΦs, the P-SEP level of the culture supernatant was high. Notably, we demonstrated, for the first time, the intracellular kinetics of P-SEP production by M1 MΦs via NET phagocytosis: M1 MΦs produced P-SEP intracellularly 15 min after NET phagocytosis and then released it extracellularly. In a sepsis mouse model, the blood NET ratio and P-SEP levels, detected using ELISA, were significantly increased (p < 0.0001). Intracellular P-SEP analysis via flow cytometry demonstrated that lung, liver, and kidney MΦs produced large amounts of P-SEP. Therefore, we identified these organs as the origin of M1 MΦs that produce P-SEP during sepsis. Our data indicate that the P-SEP level reflects the trend of NETs, suggesting that monitoring P-SEP can be used to both assess NET-induced organ damage in the lungs, liver, and kidneys during sepsis and determine treatment efficacy.

[A Case of Intrahepatic Cholangiocarcinoma and Early Postoperative Recurrences Using Comprehensive Genome Profiling to Implement Effective Treatment].

Subsequent to a medical examination, a 61-year-old male was referred to our hospital with jaundice. He was diagnosed with intrahepatic cholangiocarcinoma involving the hepatic hilum and was referred to our department to undergo a left trisectionectomy of the liver, extrahepatic bile duct resection, and regional lymphadenectomy. He was discharged on postoperative day 39 without liver failure. Two months postoperatively, positron-emission tomography/computed tomography(PET/ CT)indicated recurrences in the bone, and paraaortic lymph node. Gemcitabine and cisplatin combination first-line therapy was administered. Disease progression occurred after 4 courses of therapy. Gene panel testing was performed and the patient was switched to pembrolizumab owing to high microsatellite instability. After 2 courses of pembrolizumab, notable shrinkage of the paraaortic lymph node recurrence was confirmed on computed tomography as well as a partial response. PET-CT revealed disappearance of abnormal accumulation in all lesions at 20 months postoperatively. This has been sustained for 24 months following surgery without remarkable immune-related side-effects.

A case of chronic expanding hematoma mimicking a cystic pancreatic tumor.

BACKGROUND: A chronic expanding hematoma is an uncommon entity described as an organized blood collection that increases in size after the initial hemorrhagic event without histological neoplastic features. The standard treatment is complete resection. To our knowledge, this is the first report of a chronic expanding hematoma mimicking a pancreatic cystic tumor that has been successfully resected utilizing a laparoscopic approach. CASE PRESENTATION: We report the case of a 32-year-old man with a 10-cm chronic expanding hematoma that was preoperatively diagnosed as a cystic pancreatic tumor. Dynamic computed tomography revealed a cyst at the inferior part of the uncinate process of the pancreas without contrast enhancement. His blood biochemical data were within normal limits. The operation initially utilized a laparoscopic approach; however, the procedure was converted to hand-assisted laparoscopic surgery due to capsule adherence to surrounding organs and finally, enucleation of the tumor was performed. Pathological findings revealed a chronic expanding hematoma in the retroperitoneal space. CONCLUSION: Chronic expanding hematoma in the retroperitoneal space is so rare and sometimes adheres to the surrounding tissue. It is difficult to distinguish hematoma attaching pancreas and pancreatic cyst preoperatively. In rare cases such as this, hand-assisted laparoscopic surgery is a feasible, less invasive procedure for facilitating complete resection and preventing recurrence.

Novel endoscopic duodenal observation protocol based on Seven Pictures Rule for detecting duodenal neoplasms during esophagogastroduodenoscopy: Prospective observational study.

OBJECTIVES: No protocol for esophagogastroduodenoscopic examination of the duodenum has been established. We examined the feasibility and ability to detect neoplasms of a novel duodenal examination protocol. METHODS: This was a two-facility, prospective, observational study. Our protocol, the Seven Pictures Rule (7PR), requires pictures of the following seven locations: anterior and posterior to the bulb, area of and contralateral to the superior duodenal angle, area of and contralateral to the ampulla, and the transverse duodenum. The primary outcome was rate of completion of 7PR. Secondary outcomes were overall rates of detecting neoplasms, rates of detecting neoplasms for each location, examination time, and completion rates for standard or ultrathin endoscopes. RESULTS: There were 1549 participants. The 7PR completion rate was 81.1% and the detection rates of overall neoplasms, adenomas, and carcinomas were 0.84%, 0.71%, and 0.06%, respectively. The area in which most neoplasms was detected was contralateral to the ampulla (69.2%), and the fewest the transverse duodenum (0%). Mean duration of duodenal examination was 53.1 s. Completion rates for standard vs. ultrathin were 84.4% (1077/1276) vs. 65.6% (179/273) (P < 0.01), respectively. CONCLUSIONS: Seven Pictures Rule is acceptable for duodenal examination and a potential quality indicator.

Hybrid Train-The-Trainer course for the Fundamental Use of Surgical Energy certificates improves self-confidence in knowledge of surgical energy and develops teaching skills: a feasibility study.

BACKGROUND: Several well-trained expert instructors who completed the "Train-The-Trainer (TTT)" course are required to disseminate the safe use of surgical energy devices, which can be learned through the Fundamental Use of Surgical Energy (FUSE) program. This study aimed to explore whether the hybrid FUSE TTT course is feasible and effective, which can improve teaching skills of surgical energy. METHODS: The hybrid TTT course, which was designed to train FUSE-certified personnel as instructors, comprised three virtual sessions spread over 5 h in total and a 1-day in-person training, followed by a 100-min FUSE electrosurgery hands-on workshop in practice as an instructor. The participants reported on self-confidence regarding knowledge of various energy devices or adverse events before, immediately after, and 6 months after the course. Participants and experienced FUSE instructors assessed the trainees' presentation skills at the beginning of the in-person training and after the hands-on workshop. The primary outcomes were the feasibility and completion rate of the entire course. RESULTS: Seventeen participants completed the entire couse; most (94%) were satisfied with the course. Self-confidence in knowledge about various contents improved significantly: the fundamentals of electrosurgery (post, p < 0.001; 6 months, p = 0.01), mechanism and prevention of adverse events (post, p = 0.001; 6 months, p = 0.04), monopolar instruments (post, p = 0.002; 6 months, p = 0.01), bipolar instruments (post, p = 0.01; 6 months, p = 0.06), and integration with other medical devices (post, p = 0.006; 6 months, p = 0.02). The presentation skill index scores of self- and peer assessments improved after the in-person training (self-assessment [pre 44 vs. post 56, p < 0.001], peer assessment [pre 39 vs. post 68, p < 0.001]). CONCLUSIONS: The hybrid TTT course can provide FUSE-certified personnel with an improved self-confidence concerning knowledge of surgical energy and improve their presentation skills with midterm retention. This can help build trainees' self-confidence as instructors.

A Novel Fluorescence-Based Leak Test Method for Rectal Anastomoses Using Aerosolized Indocyanine Green.

BACKGROUND: The intraoperative air leak test is commonly performed during rectal surgery to evaluate anastomotic integrity. However, its drawbacks include occasional difficulties in visualizing the exact point of the leak while maintaining the pelvis under saline, the need for repeat testing to identify the leak point, and a lack of continuous visualization of the leak point. OBJECTIVE: To evaluate the feasibility and clinical applicability of using aerosolized indocyanine green, a fluorescent tracer, for detecting rectal anastomotic leakage. DESIGN: Animal preclinical study. SETTING: Animal laboratory at Kagawa University. PATIENTS: Six healthy adult female beagles were included. INTERVENTIONS: An anastomotic leakage model with a single air leak point was created in each dog. Indocyanine green was aerosolized using a nebulizer kit with a stream of carbon dioxide flowing at 1.5 to 2.0 L/min. The aerosol was administered into the rectum transanally, and laparoscopic observations were performed. MAIN OUTCOME MEASURES: Air leak points were observed using a near-infrared fluorescence laparoscope, after which the presence of corresponding indocyanine green fluorescence was verified. RESULTS: Aerosolized indocyanine green was visualized laparoscopically at all anastomosis sites but not elsewhere. The median time from the administration of the aerosol to its visualization was 4.5 seconds. Pathological examinations were performed 4 weeks postsurgery in all dogs, and no histological abnormalities related to aerosolized indocyanine green administration were observed at the anastomosis sites. LIMITATIONS: The leak points were surgically created and did not occur naturally. CONCLUSIONS: Visualization of air leaks at the sites of rectal anastomosis was laparoscopically achievable by administering aerosolized indocyanine green transanally into the rectum in our canine model. This novel fluorescent leak test could be a valid alternative to established methods.

Disease Activity and Progression of Disability in Multiple Sclerosis Patients Aged Over 50 With or Without Disease-Modifying Drug Treatment: A Retrospective Cohort Study.

Background This study aimed to clarify the need for disease-modifying drug (DMD) treatment in elderly patients with multiple sclerosis (MS) aged 50 years or older. MS is an autoimmune, demyelinating disease of the central nervous system that predominantly affects young women. Various DMDs are effective in preventing relapses and slowing the progression of disability in patients with MS. Although disease activity in MS is believed to decrease with aging, a consensus on the appropriate DMD treatment for elderly patients with MS is lacking. Methodology This study included elderly patients with MS (>50 years old). We compared the occurrence of relapses, worsening of disability, and conversion to secondary progressive MS (SPMS) between patients with DMD treatment and those without. Logistic regression analysis was performed to determine the predictors of these outcomes. Confounding factors were adjusted using propensity scores. Results From January 1991 to October 2022, 76 elderly patients with MS were included. The mean age at the last visit was 57.4 ± 6.3 years, with 51 patients being female. The mean age of onset of MS was 37.1 ± 10.1 years. Fifty-four patients were included in the DMD treatment group. The overall relapse rate was 38% (33% and 48% in the DMD treatment and untreated groups, respectively). No significant differences in relapse rates (p = 0.72) or in the Expanded Disability Status Scale (EDSS) scores were identified between the two groups. Kaplan-Meier curves showed no differences in the time to first relapse within five years between the two groups. Additionally, no significant predictors of relapse were identified. Among 61 patients with relapsing-remitting MS, 25% converted to SPMS during the observation period. Logistic regression analysis showed that older age at the final visit and the presence of brainstem lesions at the age of 50 years were associated with a higher rate of transition to SPMS. Conclusions In the present study, no significant difference was found in the rate of relapse, disability progression, and conversion to SPMS between the DMD treatment and untreated groups in elderly patients with MS. Therefore, in patients without long-term relapse, no poor prognostic functional factors or predictors of conversion to SPMS, discontinuation of DMDs may be considered. In addition, the presence of brainstem lesions at 50 years of age may predict the conversion to SPMS. Thus, the continuation of DMD or conversion to an appropriate DMD should be considered in patients with brainstem lesions at 50 years of age.

Terahertz radiation by quantum interference of excitons in a one-dimensional Mott insulator.

Nearly monocyclic terahertz waves are used for investigating elementary excitations and for controlling electronic states in solids. They are usually generated via second-order optical nonlinearity by injecting a femtosecond laser pulse into a nonlinear optical crystal. In this framework, however, it is difficult to control phase and frequency of terahertz waves. Here, we show that in a one-dimensional Mott insulator of a nickel-bromine chain compound a terahertz wave is generated with high efficiency via strong electron modulations due to quantum interference between odd-parity and even-parity excitons produced by two-color femtosecond pulses. Using this method, one can control all of the phase, frequency, and amplitude of terahertz waves by adjusting the creation-time difference of two excitons with attosecond accuracy. This approach enables to evaluate the phase-relaxation time of excitons under strong electron correlations in Mott insulators. Moreover, phase- and frequency-controlled terahertz pulses are beneficial for coherent electronic-state controls with nearly monocyclic terahertz waves.

Outcomes of Endoscopic Intervention Using Over-the-Scope Clips for Anastomotic Leakage Involving Secondary Fistula after Gastrointestinal Surgery: A Japanese Multicenter Case Series.

BACKGROUND: The over-the-scope clip (OTSC) is a highly effective clipping device for refractory gastrointestinal disease. However, Japanese data from multicenter studies for anastomotic leakage (AL) involving a secondary fistula after gastrointestinal surgery are lacking. Therefore, this study evaluated the efficacy and safety of OTSC placement in Japanese patients with such conditions. METHODS: We retrospectively collected data from 28 consecutive patients from five institutions who underwent OTSC-mediated closure for AL between July 2017 and July 2020. RESULTS: The AL and fistula were located in the esophagus (3.6%, n = 1), stomach (10.7%, n = 3), small intestine (7.1%, n = 2), colon (25.0%, n = 7), and rectum (53.6%, n = 15). The technical success, clinical success, and complication rates were 92.9% (26/28), 71.4% (20/28), and 0% (0/28), respectively. An age of <65 years (85.7%), small intestinal AL (100%) and colonic AL (100%), defect size of <10 mm (82.4%), time to OTSC placement > 7 days (84.2%), and the use of simple suction (78.9%) and anchor forceps (80.0%) were associated with higher clinical success rates. CONCLUSION: OTSC placement is a useful therapeutic option for AL after gastrointestinal surgery.

A quantum chemical study on the anti-SARS-CoV-2 activity of TMPRSS2 inhibitors.

Nafamostat and camostat are known to inhibit the spike protein-mediated fusion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by forming a covalent bond with the human transmembrane serine protease 2 (TMPRSS2) enzyme. Previous experiments revealed that the TMPRSS2 inhibitory activity of nafamostat surpasses that of camostat, despite their structural similarities; however, the molecular mechanism of TMPRSS2 inhibition remains elusive. Herein, we report the energy profiles of the acylation reactions of nafamostat, camostat, and a nafamostat derivative by quantum chemical calculations using a combined molecular cluster and polarizable continuum model (PCM) approach. We further discuss the physicochemical relevance of their inhibitory activity in terms of thermodynamics and kinetics. Our analysis attributes the strong inhibitory activity of nafamostat to the formation of a stable acyl intermediate and its low activation energy during acylation with TMPRSS2. The proposed approach is also promising for elucidating the molecular mechanisms of other covalent drugs.

Internal hernia after laparoscopic sigmoidectomy with splenic flexural mobilization and high ligation of the inferior mesenteric vein: A case report.

Several studies have recently reported the rare occurrence of internal herniation of the small bowel after laparoscopic colorectal surgery. Most cases of internal herniation after laparoscopic colorectal surgery occur due to a mesenteric defect. However, there have been no reports on the indications for closing mesenteric defects to prevent the development of an internal hernia. This study reports a case of an internal hernia of the proximal jejunum near the ligament of Treitz in a patient who underwent laparoscopic sigmoidectomy with splenic flexural mobilization and high ligation of the inferior mesenteric vein. Assessing the risk for internal herniation before completing the initial surgery is crucial. Additionally, mesenteric defect closure should be performed to prevent the development of internal hernias among patients with a potential risk.

Autopsy Findings of Severe COVID-19 Pneumonia Combined with Pulmonary Aspergillosis, Pneumothorax, and Pulmonary Thromboembolisms.

BACKGROUND COVID-19-associated pulmonary aspergillosis (CAPA), acute respiratory distress syndrome (ARDS), pulmonary thromboembolism (PTE), and pneumothorax are complications in severe COVID-19 patients. CASE REPORT A 64-year-old Japanese man was diagnosed with COVID-19. His past medical history included uncontrolled diabetes mellitus. He had no vaccination for COVID-19. Despite oxygen inhalation, remdesivir, dexamethasone (6.6 mg per day), and baricitinib (4 mg per day for 12 days), the disease progressed. The patient was supported with mechanical ventilation. Dexamethasone was switched to methylprednisolone (1000 mg per day for 3 days, and then reduced by half every 3 days), and intravenous heparin was initiated. Voriconazole (800 mg on the first day and then 400 mg per day for 14 days) was also started because Aspergillus fumigatus was detected in intratracheal sputum. However, he died of respiratory failure. Pathological findings of autopsy showed: (1) diffuse alveolar damage in a wide area of the lungs, which is consistent with ARDS due to COVID-19 pneumonia, (2) PTEs in peripheral pulmonary arteries, (3) CAPA, and (4) pneumothorax induced by CAPA. These conditions were all active states, suggesting that the treatments were insufficient. CONCLUSIONS Autopsy revealed active findings of ARDS, PTEs, and CAPA in a severe COVID-19 patient despite heavy treatment for each condition. CAPA can be a cause of pneumothorax. It is not easy to improve these conditions simultaneously because their treatments can induce antagonizing biological actions. To prevent severe COVID-19, it is important to reduce risk factors, such as by vaccination and appropriate blood glucose control.

Comparison of endoscopic closure versus non-closure for post-gastric endoscopic submucosal dissection artificial floor in antithrombotic therapy: a propensity score-matched analysis.

Background: The management of delayed bleeding after gastric endoscopic submucosal dissection (ESD) is currently an important issue because of recent increases in the number of patients on antithrombotic therapy. Artificial ulcer closure has been shown to prevent delayed complications in the duodenum and colon. However, its effectiveness in cases involving the stomach remains unclear. In this study, we aimed to determine whether endoscopic closure reduces post-ESD bleeding in patients undergoing antithrombotic therapy. Methods: We retrospectively analyzed 114 patients who had undergone gastric ESD while on antithrombotic therapy. The patients were allocated to one of 2 groups: a closure group (n=44) and a non-closure group (n=70). Endoscopic closure had been performed using multiple hemoclips or using the endoscopic ligation with O-ring closure method after coagulation of exposed vessels on the artificial floor. Propensity score matching resulted in 32 pairs of patients (closure vs. non-closure 32:32). The primary outcome was post-ESD bleeding. Results: The post-ESD bleeding rate was significantly lower in the closure group (0%) than in the non-closure group (15.6%) (P=0.0264). There were no significant differences between the 2 groups regarding white blood cell count, C-reactive protein, maximum body temperature, or scores on a verbal rating scale that assesses the degree of abdominal pain. Conclusion: Endoscopic closure may contribute to decreasing the incidence of post-ESD gastric bleeding in patients undergoing antithrombotic therapy.

Comparison of Needle Knife versus Scissors Forceps for Colorectal Endoscopic Submucosal Dissection: A Prospective Randomized Study.

BACKGROUND AND AIM: To evaluate the efficacy and safety of a grasping-type knife, called Clutch Cutter (CC), for colorectal endoscopic submucosal dissection (C-ESD). METHODS: This was a randomized prospective study. Patients who underwent C-ESD for colorectal neoplasms >20 mm and <50 mm in size were enrolled, dividing into two groups: ESD using needle type of dual knife alone (D-group) and circumferential incision using dual knife followed by submucosal dissection using CC (CC-group). The primary outcome was the self-completion rate. The secondary outcomes were intraoperative complication rate, procedure time, and en bloc resection rate. RESULTS: A total of 45 patients were allocated to the D-group and 43 to the CC-group were allocated. The self-completion rate was higher in the CC-group (87% [39/45] vs. 98% [42/43]). All of the six patients with an incomplete procedure in the D-group were completely resected with CC use. The intraoperative complication rate was not significant in either group (D vs. CC: 2% vs. 0%). The mean procedure time was significantly shorter in the D-group than that in the CC-group (62.0 vs. 81.1 min; p = 0.0036). The en bloc resection rate was 100% in the D-group and 98% in the CC-group. CONCLUSIONS: While dual knife use is superior to CC in terms of time efficiency, the use of CC may be a safe and efficacious option for achieving complete C-ESD.

Comparison of purse-string suture versus over-the-scope clip for gastric endoscopic full-thickness closure: traction and leak pressure testing in ex vivo porcine model.

BACKGROUND: The recently developed endoscopic full-thickness resection technique requires reliable closure. The main closure methods are the purse-string suture (PSS) technique and over-the-scope clip (OTSC) technique; however, basic data on the closure strength of each technique are lacking. This study was performed to compare the closure strengths of these two methods in an ex vivo porcine model. METHODS: In the traction test, a virtual 5-cm full-thickness closure line was closed by the following six methods three times each: conventional hemoclips, mucosal PSS, seromuscular PSS, mucosal OTSC, seromuscular OTSC, and surgical suture. The primary endpoint was the tension at the starting point of dehiscence, measured in Newtons (N) by an automatic traction machine. In the leak test, a 15-mm gastric full-thickness defect was closed by PSS or OTSC six times each, and the closed stomach was then pressurized in a water container. The primary endpoint was the leak pressure when air bubbles appeared. The secondary endpoints were the procedure time and presence of complete inverted closure. RESULTS: The mean tension was 2.16, 3.68, 5.15, 18.30, 19.30, and 62.40 N for conventional hemoclips, mucosal PSS, seromuscular PSS, mucosal OTSC, seromuscular OTSC, and surgical suture, respectively. Complete inverted closure was observed for seromuscular PSS, seromuscular OTSC, and surgical suture. The mean leak pressure was 13.7 and 24.8 mmHg in the PSS and OTSC group, respectively (P < 0.01). The mean procedure time was 541 and 169 s in the PSS and OTSC group, respectively (P < 0.01). Complete inverted closure was observed in OTSC alone. CONCLUSION: The OTSC, which allows complete inverted closure, showed greater closure strength than PSS. Considering the size limitation suitable for single OTSC, a therapeutic strategy for closing the larger size is further warranted.