Preoperative fluorescent clip marking vs. India ink tattooing for tumor identification during colorectal surgery.

PURPOSE: Identifying tumor location is important in colorectal tumor resection. Preoperative endoscopic India ink marking is a widespread practice, but local injection of ink is an unstable procedure. Although it is often invisible, the ink may be sprayed into the peritoneal cavity and contaminate the surgical field. At our hospital, we introduced fluorescent clip marking (FCM) using the Zeoclip FS®, an endoscopic clip developed using near-infrared fluorescent resin. We tested the usefulness of FCM by retrospectively comparing cases in which FCM was used with cases in which conventional ink marking was used. METHODS: We enrolled 305 patients with colorectal tumors who underwent colorectal surgery after preoperative marking from January 2017 to April 2022. We classified the patients into the FCM group (86 patients) and the India ink tattoo group (219 patients). Endoscopic marking was completed in the FCM group by the day before surgery, and fluorescence was evaluated during surgery with a fluorescent laparoscopic system. Patient backgrounds, marking visibility, adverse effects, and early postoperative results were retrospectively compared between groups. RESULTS: Marking was visually confirmed in 80 patients in the FCM group (93.02%) and in 166 patients in the India ink tattoo group (75.80%) (p = 0.0006). In the group with India ink tattoos, contamination of the surgical field was observed in seven cases (3.20%). No adverse events were observed in the FCM group. CONCLUSION: In colorectal surgery, FCM provides better visibility than the conventional India ink tattooing method and is a simple and safe marking method. CLINICAL TRIAL REGISTRATION: Examination of fluorescence navigation for laparoscopic colorectal cancer surgery. Research Ethics Committee of the Kawaguchi Municipal Medical Center (Saitama, Japan) approval number: 2020-3. https://kawaguchi-mmc.org/wp-content/uploads/clinicalresearch-r02.pdf .

Chemical Structures and Anti-proliferative Effects of Valeriana fauriei Constituents on Cancer Stem Cells.

We isolated the new sesquiterpenes, valerianaterpenes IV and V, and the new lignans valerianalignans I-III from the methanol extracts of the rhizomes and roots of Valeriana fauriei and elucidated their structures based on chemical and spectroscopic findings. The absolute configuration of valerianaterpene IV and valerianalignans I-III were established by comparing experimental and predicted electronic circular dichroism (ECD) data. Among the isolated compounds, valerianalignans I and II exerted anti-proliferative activity against human astrocytoma cells (U-251 MG) and their cancer stem cells (U-251 MG CSCs). Interestingly, valerianalignans I and II notably exerted anti-proliferative activities at lower concentrations against CSCs than non-CSCs, and the absolute configurations of these compounds affected their activities.

Fluorescence angiography vs. direct palpation for bowel viability evaluation with strangulated bowel obstruction.

PURPOSE: In surgery for strangulated bowel obstruction, intestinal blood flow (IBF) is usually evaluated by observing bowel colour, peristalsis, intestinal temperature and arterial pulsations in the mesentery. We investigated whether indocyanine green (ICG) fluorescence angiography (ICG-FA) is an effective alternative to palpation. METHODS: Thirty-eight patients who underwent emergency surgery for strangulated bowel obstruction from January 2017 to April 2021 were divided into two groups: (i) the ICG + group, in which ICG was used during laparoscopic surgery (n = 16), and (ii) the ICG - group, in which palpation without ICG was used during open surgery (n = 22). Starting in July 2019, ICG and laparoscopic surgery were applied in all cases except emergency cases when the fluorescence laparoscope was not ready. Surgical outcomes and patient characteristics were compared. RESULTS: Patient characteristics, the operative duration and postoperative hospitalization duration did not significantly differ between the groups. Bowel resection was performed in 4 cases (25%) among ICG + patients and 11 cases (50%) among ICG - patients. The ratios of pathological findings (ischaemia:mucosal necrosis:transmural necrosis) were 0:2:2 and 1:6:4 in the two groups, respectively. Blood loss was measured with gauze and suction tubes and was 1 (0-5) mL in the ICG + group and 12.5 (0-73) mL in the ICG - group (p = 0.002). Postoperative complications occurred in 1 case (6.3%) in the ICG + group and 9 cases (40.9%) in the ICG - group (p = 0.025). CONCLUSION: Although there were few intestinal resections in the ICG + group, the rate of pathological necrosis tended to be high, and no complications due to ineligibility were noted in the intestinal preservation group. During laparoscopic surgery, ICG-FA is useful as a substitute for palpation and has the potential to improve surgical outcomes. CLINICAL TRIAL REGISTRATION: Research Ethics Committee of the Kawaguchi Municipal Medical Center (Saitama, Japan) approval number: 2019-40.

Fluorescence vessel and ureter navigation during laparoscopic lateral lymph node dissection.

BACKGROUND: Lateral lymph node metastasis in lower rectal cancer is considered a local disease in Japan, and guidelines suggest lateral lymph node dissection (LLND). However, laparoscopic procedures are relatively difficult. The ureter and hypogastric fascia must be dissected from the vesicohypogastric fascia to preserve the autonomic nerve and ureter. Additionally, lymph node dissection around the internal iliac artery is complex because many patterns of branching from the internal iliac artery exist. We investigated the utility of fluorescence ureter and vessel navigation using a near-infrared ray fluorescent ureteral catheter (NIRFUC) and indocyanine green (ICG). METHODS: Fourteen patients who underwent laparoscopic LLND using fluorescence navigation were included. Eleven patients had rectal cancer, 1 had anal cancer, and 2 exhibited recurrence of rectal cancer. Eleven patients underwent NIRFUC insertion before surgery. Fluorescence vessel navigation (FVN) was performed with intraoperative ICG injections in 14 patients, with a total of 18 sides. The outcome measures were ureter navigation visibility, detection of the branch form from the internal iliac artery with FVN, differences between the fluorescence findings and anatomy of the internal iliac artery determined after LLND, and the surgical outcome. RESULTS: In all 11 patients, the ureters were clearly identified as fluorescent before dissection around the ureter. FVN revealed the internal iliac, umbilical, and superior vesical arteries in all patients. The branch from the internal iliac artery according to the Adachi classification was revealed on 16 sides (89%). The time from intravenous ICG injection to fluorescence of the internal iliac artery was 38 (17-57) s. The time from intravenous injection to when the vessels were observed as fluorescent was 113 (65-661) s. No ureteral or vessel injuries occurred. CONCLUSIONS: Fluorescence navigation of vessels and the ureter is feasible in laparoscopic LLND and has the potential to increase safety. CLINICAL TRIAL REGISTRATION: Examination of fluorescence navigation for laparoscopic colorectal cancer surgery Research Ethics Committee of the Kawaguchi Municipal Medical Center (Saitama, Japan) approval number: 2020-3. https://kawaguchi-mmc.org/wp-content/uploads/clinicalresearch-r02.pdf.

Anti-Proliferative Effects of Iridoids from Valeriana fauriei on Cancer Stem Cells.

We isolated seven new iridoid glucosides (valerianairidoids I-VII; 1-3, 6, 7, 9, and 12) and six known compounds from the methanol extract of the dried rhizomes and roots of Valeriana fauriei. Chemical and spectroscopic data were used to elucidate the chemical structures of the seven new iridoid glucosides, and their absolute configurations were determined by comparing their electronic circular dichroism (ECD) spectra with those determined experimentally. Aglycones 1a, 6a, and 9a, which were obtained by enzymatic hydrolysis of the isolated iridoid glucosides, exhibited anti-proliferative activities against cancer stem cells (CSCs) established by a sphere-formation assay using human breast cancer (MDA-MB-231) and human astrocytoma (U-251MG) cells. Interestingly, these iridoids selectively showed anti-proliferative activities against CSCs from MDA-MB-231 cells. These results suggest that the iridoids obtained in this study may have potency as a breast cancer treatment and as preventive agent via exterminating CSCs.

Linderapyrone: A Wnt signal inhibitor isolated from Lindera umbellata.

Linderapyrone, a Wnt signal inhibitor was isolated from the methanolic extract of the stems and twigs of Lindera umbellata together with epi-(-)-linderol A. Linderapyrone inhibited TCF/ß-catenin transcriptional activity that was evaluated using cell-based TOPFlash luciferase assay system. To evaluate the structure-activity relationship and mechanism, we synthesized linderapyrone and its derivatives from piperitone. As the results of further bioassay for synthesized compounds, we found both of pyrone and monoterpene moieties were necessary for inhibitory effect. cDNA microarray analysis in a linderapyrone derivative treated human colorectal cancer cells showed that this compound downregulates Wnt signaling pathway. Moreover, we successes to synthesize the derivative of linderapyrone that has stronger inhibitory effect than linderapyrone and ICG-001 (positive control).

Structures and Antimutagenic Effects of Onoceranoid-Type Triterpenoids from the Leaves of Lansium domesticum.

A methanol extract of the dried leaves of Lansium domesticum showed antimutagenic effects against 3-amino-1,4-dimethyl-5 H-pyrido[4,3- b]indole (Trp-P-1) and 2-amino-1-methyl-6-phenylimidazo[4,5- bI]pyridine (PhIP) using the Ames assay. Nine new onoceranoid-type triterpenoids, lansium acids I-IX (1-9), and nine known compounds (10-16) were isolated from the extract. The structures of the new compounds were elucidated on the basis of chemical and spectroscopic evidence. The absolute stereostructures of the new compounds were determined via their electronic circular dichroism spectra. Several isolated onoceranoid-type triterpeneoids showed antimutagenic effects in an in vitro Ames assay. Moreover, oral intake of a major constituent, lansionic acid (10), showed antimutagenic effects against PhIP in an in vivo micronucleus test.

Relationship between knee osteoarthritis and the locomotive syndrome risk tests: A cross-sectional study.

OBJECTIVE: To determine the relationship between locomotive syndrome (LS) risk tests and knee osteoarthritis (KOA). STUDY DESIGN: Cross-sectional cohort study. METHODS: In 2015, 225 people (male 84, females 141, mean age 67.9, range 30-90) were examined using LS risk tests, including the stand-up test, the two-step test, and the 25-question risk assessment, in Katashina Village in Gunma prefecture. The Japanese orthopaedic association defined LS risk test stage 1, difficulty with standing from a 40-cm-high seat using one-leg in the stand-up test, two-step test <1.3, the 25-question risk assessment ≧7, and defined stage 2, difficulty with standing from a 20-cm-high seat using both legs in the stand-up test, two-step test <1.1, the 25-question risk assessment ≧16. Persons with two or more of the following on the ultrasound (US) assessment were defined as having KOA: peripheral joint space (PJS) < 5 mm during weight-bearing; medial radial displacement (MRD) > 5 mm during weight-bearing; and osteophytes > 2 mm. If the residents had KOA in either knee, they were defined as having KOA. RESULTS: 45 residents had KOA in either knee. Logistic regression analysis adjusted for age, height, weight, gender, and knee pain was performed with stage 0 as reference. On the stand-up test, the odds ratio was 5.484 (95% confidence interval (CI) 1.966-15.297) for stage 1 and 2.067 (95% CI 0.426-10.017) for stage 2. On the two-step test, the odds ratio was 1.497 (95% CI 0.557-4.021) for stage 1 and 0.71 (95% CI 0.210-2.395) for stage 2. On the 25-question risk assessment, the odds ratio was 1.73 (95% CI 0.646-4.631) for stage 1 and 1.5 (95% CI 0.508-4.433) for stage 2. CONCLUSIONS: A stand-up test of stage 1 had a significant relationship with KOA. This might suggest that proper care of KOA is needed to prevent progressive disability.

Cytotoxic activities of alkaloid constituents from the climbing stems and rhizomes of Sinomenium acutum against cancer stem cells.

From the methanolic extract of the climbing stems and rhizomes of Sinomenium acutum, two new aporphine analogues, acutumalkaloids I and II, were isolated together with fifteen known compounds including lysicamine. The chemical structures of the isolated new compounds were elucidated based on chemical/physicochemical evidence such as NMR and MS spectra. For acutumalkaloids I and II, the absolute configurations were established by comparison of experimental and predicted electronic circular dichroism (ECD) data. We compared anti-proliferative activities of isolated compounds with reported naturally occurring Wnt/ß-catenin pathway inhibitor, nuciferine. Among the isolated compounds, we found lysicamine have anti-proliferative activity against both of HT-29 human colon cancer cell line and its cancer stem cells (CSCs). The IC50 values of lysicamine against non-CSCs and its CSCs were lower than that of nuciferine. In addition, the results of western blotting analysis suggested that lysicamine inhibited the expression of Wnt/ß-catenin pathway target protein such as survivin. These results suggested that lysicamine show cytotoxic activity via inhibition of Wnt/ß-catenin pathway.

Surgical Outcomes of Adults with Spinal Caries from 1992 to 2019: A Single-Center Study-Risk Factors for the Progression of Kyphosis after Anterior Spinal Fixation Reveal Cases Needing Additional Posterior Instrumentation.

Background: This study aims to investigate the postoperative improvement of paralysis, fusion rate and risk factors for kyphosis progression in adults affected with spinal caries. Methods: Overall, 134 patients with spinal caries from the thoracic to lumbar spine from 1992 to 2021 were included in this study. Data concerning the affected level (thoracic, thoracolumbar, lumbar, and lumbosacral), bone fusion rate, and progression of the postoperative local kyphosis angle were collected. The risk factors for the progression of local kyphosis angle after anterior spinal fixation (ASF) were determined using linear regression analysis. Results: Preoperatively, the degree of spinal cord paralysis was D and E on Frankel classification. Improvement of paralysis was good with surgery, especially from C, D. The overall bone fusion rate was 83.2%. The only factor influencing the progression of local kyphosis angle after ASF was the level of the affected vertebra. Progression of kyphosis angle after ASF was very advanced in the thoracolumbar transition area. Conclusions: Surgical improvement in paraplegia and the fusion rate of ASF with only grafted bone was good. However, in patients affected in the thoracolumbar spine region, posterior instrumentation is desirable because of local kyphosis progression risk after surgery.

Impact of Frailty on Functional Improvement Following Traumatic Spinal Cord Injury: A Japanese Single-Center Experience.

Study Design: This is a retrospective case series study. Objective: The aim of this study was to investigate whether frailty contributes to functional recovery in individuals with spinal cord injury (SCI). Methods: A total of 121 patients with SCI (106 cervical SCI, 15 thoracic SCI) discharged from our center over the past three years were studied. Moreover, 11-factor modified frailty index (mFI) scores, the length of hospital stays, the rate of returning home, and improvement in Spinal Cord Independence Measure (SCIM) scores were assessed retrospectively. Results: The average age at the time of injury for all 121 cases was 59.6 years. Based on pre-injury assessments, 24 cases were categorized as the Frail group, and 97 cases were categorized as the Robust group. The Frail group had SCIM improvement rates of 16.7% and a home discharge rate of 45.8%. In contrast, the Robust group had SCIM improvement rates of 33.5% and a home discharge rate of 68.0%, with statistically significant differences between the two groups. A significant negative correlation was observed between mFI scores and SCIM improvement rates (R = -0.231, p = 0.014). Conclusions: This study suggests that individuals with pre-existing frailty before SCI experience poorer SCIM improvement rates and face challenges in returning home.

Pelvic Incidence As a Predictor of Proximal Junctional Kyphosis in Patients with Lenke type 5 Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective comparative study. OBJECTIVE: To evaluate the relationship between pelvic incidence (PI) and proximal junctional kyphosis (PJK) in patients with Lenke type 5 adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Although PJK is a common complication of sagittal malalignment after posterior correction and fusion surgery (PSF), few studies have assessed its risk factors. The significance of pelvic morphology in relation to PJK has been suggested but remains unclear in Lenke type 5 AIS patients. METHODS: A total of 92 patients with Lenke type 5 AIS who underwent selective thoracolumbar PSF with a minimum follow-up of two years were included. Patients were divided into PJK and non-PJK groups based on postoperative radiographs. The influence of PI on PJK occurrence was evaluated through binary logistic analysis. Subgroup analysis was performed based on the PI value (low PI,<45°; high PI, ≥ 45°) to identify factors affecting PJK occurrence. RESULTS: PJK was observed in 17.4% of the whole cohort. Binary logistic regression analysis identified low PI and large TL/L curve as a risk factor for PJK (PI, odds ratio, 0.933; TL/L curve, odds ratio, 1.080). Subgroup analysis showed that the postoperative increase in the upper instrumented vertebra slope in PJK cases was comparable in both the low and high PI groups. Meanwhile, lordotic changes in the fused area in the PJK cases were observed only in the low PI group. No difference in the Scoliosis Research Society 22 scores were observed between the two groups. CONCLUSION: From this study a low PI was identified as a risk factor for the occurrence of PJK in Lenke type 5 AIS patients. The occurrence of PJK is influenced by lordotic changes in the fused area and the limited compensatory capacity of the pelvis in patients with a low PI.

Linderapyrone analogue LPD-01 as a cancer treatment agent by targeting importin7.

The Wnt/ß-catenin signaling pathway plays important roles in several cancer cells, including cell proliferation and development. We previously succeeded in synthesizing a small molecule compound inhibiting the Wnt/ß-catenin signaling pathway, named LPD-01 (1), and 1 inhibited the growth of human colorectal cancer (HT-29) cells. In this study, we revealed that 1 inhibits the growth of HT-29 cells stronger than that of another human colorectal cancer (SW480) cells. Therefore, we have attempted to identify the target proteins of 1 in HT-29 cells. Firstly, we investigated the effect on the expression levels of the Wnt/ß-catenin signaling pathway-related proteins. As a result, 1 inhibited the expression of target proteins of Wnt/ß-catenin signaling pathway (c-Myc and Survivin) and their genes, whereas the amount of transcriptional co-activator (ß-catenin) was not decreased, suggesting that 1 inhibited the Wnt/ß-catenin signaling pathway without affecting ß-catenin. Next, we investigated the target proteins of 1 using magnetic FG beads. Chemical pull-down assay combined with mass spectrometry suggested that 1 directly binds to importin7. As expected, 1 inhibited the nuclear translocation of importin7 cargoes such as Smad2 and Smad3 in TGF-ß-stimulated HT-29 cells. In addition, the knockdown of importin7 by siRNA reduced the expression of target genes of Wnt/ß-catenin signaling pathway. These results suggest that importin7 is one of the target proteins of 1 for inhibition of the Wnt/ß-catenin signaling pathway.

Human-induced pluripotent stem cell-derived neural stem/progenitor cell ex vivo gene therapy with synaptic organizer CPTX for spinal cord injury.

The transplantation of neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) has shown promise in spinal cord injury (SCI) model animals. Establishing a functional synaptic connection between the transplanted and host neurons is crucial for motor function recovery. To boost therapeutic outcomes, we developed an ex vivo gene therapy aimed at promoting synapse formation by expressing the synthetic excitatory synapse organizer CPTX in hiPSC-NS/PCs. Using an immunocompromised transgenic rat model of SCI, we evaluated the effects of transplanting CPTX-expressing hiPSC-NS/PCs using histological and functional analyses. Our findings revealed a significant increase in excitatory synapse formation at the transplantation site. Retrograde monosynaptic tracing indicated extensive integration of transplanted neurons into the surrounding neuronal tracts facilitated by CPTX. Consequently, locomotion and spinal cord conduction significantly improved. Thus, ex vivo gene therapy targeting synapse formation holds promise for future clinical applications and offers potential benefits to individuals with SCI.

Auxiliary roles of nardilysin in the early diagnosis of acute coronary syndrome: a prospective cohort study, the Nardi-ACS study.

Acute coronary syndrome (ACS) includes myocardial infarction (MI) and unstable angina (UA). MI is defined by elevated necrosis markers, preferably high-sensitivity cardiac troponins (hs-cTn). However, it takes hours for cTn to become elevated after coronary occlusion; therefore, difficulties are associated with diagnosing early post-onset MI or UA. The aim of this prospective cohort study was to examine the diagnostic ability of serum nardilysin (NRDC) for the early detection of ACS. This study consisted of two sequential cohorts, the Phase I cohort, 435 patients presenting to the emergency room (ER) with chest pain, and the Phase II cohort, 486 patients with chest pain who underwent coronary angiography. The final diagnosis was ACS in 155 out of 435 patients (35.6%) in the phase I and 418 out of 486 (86.0%) in the phase II cohort. Among 680 patients who presented within 24 h of onset, 466 patients (68.5%) were diagnosed with ACS. Serum NRDC levels were significantly higher in patients with ACS than in those without ACS. The sensitivity of NRDC in patients who presented within 6 h after the onset was higher than that of hsTnI, and the AUC of NRDC within 1 h of the onset was higher than that of hsTnI (0.718 versus 0.633). Among hsTnI-negative patients (300 of 680 patients: 44.1%), 136 of whom (45.3%) were diagnosed with ACS, the sensitivity and the NPV of NRDC were 73.5 and 65.7%, respectively. When measured in combination with hsTnI, NRDC plays auxiliary roles in the early diagnosis of ACS.

Transanal Total Mesorectal Excision for Extended Surgery in the Early Stage After Introduction.

BACKGROUND/AIM: The effectiveness of transanal total mesorectal excision (Ta-TME) in extended surgery (ES) has been discussed. This study examined the short-term outcomes of the first 31 patients who underwent Ta-TME after its introduction and verified the safety of Ta-TME in ES in the early stage following its introduction. PATIENTS AND METHODS: Thirty-one consecutive patients who underwent Ta-TME between December 2021 and January 2023 at our institution were included. The indications for Ta-TME were rectal tumors that could be palpated during rectal examination and bulky tumors that were deemed unresectable without Ta-TME. Short-term outcomes were retrospectively compared between patients who underwent normal Ta-TME, (n=27, TME group) and patients who underwent ES beyond TME (n=4, ES group). The data are shown as the median and interquartile range. Statistical analysis was performed with the Mann-Whitney U-test and Fisher's exact test. RESULTS: Total pelvic exenteration (TPE) was performed in the 4th and 8th patients; the 9th patient underwent a combined resection of the right adnexa and urinary bladder wall. The 31st patient underwent a combined resection of the uterus and the right adnexa. The operative time was 353 [285-471] vs. 569 [411-746] min for the TME and ES groups (p=0.039). Blood loss was 8 [5-40] vs. 45 [23-248] ml (p=0.065); postoperative hospital stay was 15 [10-19] vs. 11 [9-15] days (p=0.201); postoperative complications (higher than grade III) were 5 (19%) vs. 0 (p=1.000). Negative CRM was achieved in all cases. CONCLUSION: Ta-TME in ES was as safe as normal Ta-TME in the early stage after its introduction.