Composite Lymphoma after Treatment with Infliximab for Sarcoidosis and Ankylosing Spondylitis.

Lymphoid proliferations and lymphomas associated with immune deficiency and dysregulation (LP/L-IDD) are rare entities associated with the use of immunosuppressive drugs (ISD) for autoimmune conditions. Composite lymphomas, featuring both B-cell and T-cell lymphomas, are infrequent, and their occurrence as LP/L-IDD is rare. We herein report the case of a 70-year-old man with right pleural effusion and lymphadenopathy, who was treated with infliximab for sarcoidosis and ankylosing spondylitis. A biopsy revealed a composite lymphoma of DLBCL and PTCL-NOS. CHOP chemotherapy led to significant remission. This case report emphasizes the need to consider lymphoma in patients with autoimmune diseases such as sarcoidosis and ankylosing spondylitis, especially those treated with ISDs.

The effects of resistance exercise and leucine-enriched essential amino acid supplementation on muscle mass and physical function in post-gastrectomy patients: a pilot randomized controlled trial.

[Purpose] In gastric cancer patients, low muscle mass decreases overall survival and quality of life (QOL). Resistance exercise with leucine-enriched essential amino acid (LEAA) supplementation may prevent muscle mass loss. This study was aimed at determining whether resistance exercise with LEAA supplementation prevents muscle mass loss in post-gastrectomy patients. [Participant and Methods] We conducted a single-center, open-label, randomized controlled pilot trial. Ten participants who underwent gastrectomy were divided into two groups. The intervention group underwent resistance exercise at 70% of one repetition maximum and received a supplement of 3 g of LEAA twice daily for 15 days, while the control group received standard care. We compared changes in muscle mass, physical function (muscle strength and continuous walking distance), and QOL between the groups. [Results] We found good adherence and participation rates in both groups. We failed to detect a significant difference in muscle mass between the groups. The intervention group showed significant improvements in muscle strength and QOL, while the control group showed no significant changes. [Conclusion] We failed to detect a significant difference in muscle mass due to resistance exercise with LEAA supplementation in post-gastrectomy patients. However, resistance exercise with LEAA supplementation might be beneficial for muscle strength recovery and QOL improvements.

Electrode process of mobile ions in generating space-charge polarization.

Macroscopic dipole moments formed in electrolytic cells influence dielectric properties of the cells, and their magnitudes can be quantified by dielectric spectroscopy. We analyze the dielectric spectra observed for dilute electrolytic cells in low-frequency regions from two perspectives: space-charge polarization and diffuse double layers on the electrodes. The difference between the two polarization phenomena is characterized by the effective dielectric constant and the kinetic parameter introduced in the Poisson-Nernst-Planck model. The analytical results indicate that the generation of space-charge polarization is attributed to the kinetic process of mobile ions replacing solvent molecules on the electrode surface. This is an experimental confirmation of the formation process of macroscopic dipole moment due to space-charge polarization and its practical contribution to the dielectric constant of material.

Clinical course of small gastric subepithelial lesion less than 20 mm diagnosed by endoscopic ultrasound-guided fine-needle aspiration.

BACKGROUND AND AIM: Gastrointestinal stromal tumors (GISTs) are treated as malignant gastric subepithelial lesions (SELs), and resection is recommended. However, small gastric SELs < 20 mm with no malignant features are monitored without histopathological examination, and the frequency of malignancy is unknown. This study aimed to clarify the clinicopathological findings and clinical course of gastric SELs < 20 mm measured by endoscopic ultrasound (EUS). METHODS: This retrospective cohort study included consecutive patients with small gastric SELs < 20 mm diagnosed using EUS at a tertiary referral center between 2009 and 2021. The clinical course after diagnosis using EUS-guided fine-needle aspiration (EUS-FNA) was reviewed. RESULTS: Among 333 patients with small gastric SELs, 104 patients with 105 lesions underwent EUS-FNA. The pathological diagnosis was confirmed in 87 patients. GISTs were the most common pathology (47%). Among the 87 patients, 43 underwent therapeutic interventions, including tumor resection and chemotherapy. In groups of tumor resection, the pathological tumor size on the resected specimen was significantly larger than the size measured by EUS (19.5 mm vs 15.0 mm, P < 0.001), and 37% of resected SELs were 20 mm or over. No recurrence was observed after tumor resection during a mean follow-up period of 40 months. CONCLUSIONS: Approximately 40% of small gastric SELs were malignant tumors, such as GIST, with most of them requiring treatment. Additionally, considering that the EUS measurement is 5 mm smaller than the pathological tumor diameter, further examinations, such as systematic EUS-FNA, may be required for SEL, including those smaller than 20 mm.

Analgesic effect of neuromodulation using the AT-04 portable magnetic field-generating device in a patient with neuropathic pain: a case report.

BACKGROUND: Neuromodulation by magnetic field through the AT-04 (ait® (AT-04); Peace of Mind Co., Ltd., Kumamoto, Japan) has improved allodynia in neuropathic pain model rats. This report focuses on neuromodulation through magnetic field exposure using the AT-04 that provided an analgesic effect in a patient with neuropathic pain. CASE PRESENTATION: A 47-year-old man presented with flaccid paralysis and extensive neuropathic pain and scored 7 on the 11-point Numerical Rating Scale (NRS) for his left upper limb. The patient was treated with neuromodulation by magnetic field exposure using the AT-04. Baseline NRS scores were obtained three times daily during the baseline period (days 1-5). Magnetic field exposure was then performed for 30 min three times daily (morning, noon, and evening) at home for 36 days, which was termed the intervention period (days 6-41). During the baseline period, the median NRS score was 7 and the baseline NRS score for calculating the percentage of nonoverlap data (PND) was 6. During the intervention period, the median NRS score was 4 and the PND value of the NRS score was 77.8% (28/36). Neuromodulation by magnetic field exposure using the AT-04 effectively decreased the patient's NRS score. The patient had no adverse effects during the intervention period. CONCLUSIONS: Neuromodulation by magnetic field exposure using the AT-04 was effective in decreasing the NRS score in a patient with neuropathic pain. The AT-04 portable magnetic field-generating device shows potential as a therapeutic option for refractory neuropathic pain.

Impact of endoscopy intervals on metachronous gastric cancer after endoscopic submucosal dissection: Comparison between 1 year and half-a-year.

OBJECTIVES: Japanese guidelines recommend posttreatment endoscopy once or twice a year after endoscopic submucosal dissection (ESD) for early gastric cancer. However, the impact of endoscopy intervals on metachronous gastric cancer (MGC) remains unclear, especially the difference between 1-year and half-a-year intervals. We aimed to investigate this difference. METHODS: This study retrospectively investigated 2429 patients who underwent gastric ESD between May 2001 and June 2019 at our hospital. Patients who developed MGC were classified based on those who underwent the previous endoscopy within at least 7 months (short-interval group) and within 8-13 months (regular-interval group). Propensity score matching (PSM) was used to adjust for possible confounders. The primary outcome was the proportion of MGC beyond curative ESD criteria established in the guidelines. RESULTS: A total of 216 eligible patients developed MGC. The short- and regular-interval groups included 43 and 173 patients, respectively. Overall, no patients in the short-interval group had MGC beyond curative ESD criteria, while 27 patients in the regular-interval group did. The proportion of MGC beyond curative ESD criteria was significantly lower in the short-interval group than in the regular-interval group before (P = 0.003) and after (P = 0.028) PSM. Although not significant, the short-interval group tended to have a higher stomach preservation rate than the regular-interval group (P = 0.093). CONCLUSION: Our study indicated a possible benefit of biannual surveillance endoscopy in the early post-ESD period.

Predictors of severe submucosal fibrosis during endoscopic submucosal dissection in patients with ulcerative colitis: Retrospective cohort study.

OBJECTIVES: Severe submucosal fibrosis is a crucial technical difficulty encountered during endoscopic submucosal dissection (ESD) in patients with ulcerative colitis (UC). We aimed to identify predictors of severe submucosal fibrosis in patients with UC. METHODS: We retrospectively included 55 tumors resected using ESD from 48 consecutive patients with UC. We analyzed the clinicopathological characteristics and treatment outcomes between the F0/1 (none to mild submucosal fibrosis) group (n = 28) and F2 (severe submucosal fibrosis) group (n = 27). RESULTS: No significant difference was found between the F0/1 and F2 groups in en bloc resection rate (100% vs. 96%, P = 0.49), the R0 resection rate (100% vs. 93%, P = 0.24), and the dissection speed (0.18 vs. 0.13 cm2 /min, P = 0.07). Intraoperative perforation was more common in the F2 group (30%) than in the F0/1 group (8%; P = 0.01). Multivariable analysis showed that a longer duration of UC (≥10 years; odds ratio [OR] 6.11; 95% confidence interval [CI] 1.20-31.03; P = 0.03) and scarring of background mucosa of the tumor (OR 39.61; 95% CI 3.91-400.78; P < 0.01) were independent predictors of severe submucosal fibrosis. CONCLUSION: Long UC duration and scarring background mucosa were predictors of severe submucosal fibrosis associated with perforation during ESD.

Endoscopic full-thickness resection for gastric submucosal tumors: Japanese multicenter prospective study.

OBJECTIVES: Early gastric cancer endoscopic resection (ER) is prominent in Japan. However, evidence regarding ER of gastric submucosal tumors (SMT) is limited. This prospective multicenter phase II study investigated the efficacy and safety of endoscopic full-thickness resection (EFTR) for gastric SMT. METHODS: Endoscopic full-thickness resection indication for gastric SMT was 11-30 mm, histologically proven or clinically suspicious (irregular margin, increasing size, or internal heterogeneity) gastrointestinal stromal tumors (GIST), with no ulceration and intraluminal growth type. The primary end-point was the complete ER (ER0) rate, with a sample size of 42. RESULTS: We enrolled 46 patients with 46 lesions between September 2020 and May 2023 at seven Japanese institutions. The mean ± SD (range) endoscopic tumor size was 18.8 ± 4.5 (11-28) mm. The tumor resection and defect closure times were 54 ± 26 (22-125) min and 33 ± 28 (12-186) min, respectively. A 100% ER0 was achieved in all 46 patients. The EFTR procedure was accomplished in all patients without surgical intervention. One patient had delayed perforation and was managed endoscopically. GIST accounted for 76% (n = 35) of the cases. R0, R1, and RX rates were 33 (77%), 3 (6.5%), and 7 (15%), respectively. CONCLUSION: Endoscopic full-thickness resection for gastric SMT of 11-30 mm is efficacious. It warrants further validation in a large-scale cohort study to determine the long-term outcome of this treatment for patients with gastric GIST.

Endoscopic Resection with One-Port Placement: A Newly Developed Technique for the Safe Management of Advanced Endoscopic Resection for Gastric Gastrointestinal Stromal Tumors.

INTRODUCTION: Endoscopic full-thickness resection (EFTR) without laparoscopic assistance (pure EFTR) is an emerging, less invasive treatment for gastrointestinal stromal tumors (GISTs). However, the technique has seldom been performed outside China because of concerns regarding pneumoperitoneum, maintenance of endoscopic view, and endoscopic suturing. This study aimed to evaluate the efficacy and safety of endoscopic resection with one-port placement (EROPP) for gastric GISTs. METHODS: This retrospective study included 17 patients with gastric GISTs originating from the muscularis propria who underwent EROPP between 2019 and 2022. One camera port was inserted in the umbilicus before initiating the endoscopic procedure to maintain intra-abdominal pressure, which was monitored and adjusted via this port. While allowing for conversion to laparoscopic surgery if needed, EFTR was performed as follows: (1) circumferential incision of the mucosal and submucosal layers around the lesion was performed by typical endoscopic submucosal dissection; (2) an intentional perforation and subsequent seromuscular resection was made using dental floss and an endo-clip for traction; and (3) closure of the gastric full-thickness defect was performed with an over-the-scope clip (OTSC) after peroral retrieval of the specimen. We retrospectively assessed the short-term outcomes and safety. RESULTS: All procedures were completed successfully without conversion to laparoscopic surgery. The median size of the resected tumors was 23 mm (range, 8-35 mm), the median resection time was 36 min (range, 22-95 min), and closure time was 18 min (range, 10-45 min). The rates of en bloc and complete resection were 100% and 88%, respectively. In 2 cases, another port was added to aspirate the leaking fluid or check the condition of the endoscopic closure. All gastric defects were endoscopically closed, mainly using OTSCs. The recovery course for all patients was uneventful, and no adverse events were reported. CONCLUSIONS: EROPP is a safe and minimally invasive treatment for gastric GISTs and appears to be suitable for introducing EFTR procedures.

Decreased insulin-like growth factor-1 expression in response to mechanical loading is associated with skeletal muscle anabolic resistance in cancer cachexia.

OBJECTIVE: Cachexia is a systemic metabolic syndrome characterized by loss of body weight and skeletal muscle mass during chronic wasting diseases, such as cancer. Skeletal muscle in cancer cachexia is less responsive to anabolic factors including mechanical loading; however, the precise molecular mechanism is largely unknown. In this study, we examined the underlying mechanism of anabolic resistance in skeletal muscle in a cancer cachexia model. METHODS: CD2F1 mice (male, 8 weeks old) were subcutaneously transplanted (1 × 106 cells per mouse) with a mouse colon cancer-derived cell line (C26) as a model of cancer cachexia. Mechanical overload of the plantaris muscle by synergist tenotomy was performed during the 2nd week and the plantaris muscle was sampled at the 4th week following C26 transplantation. RESULTS: The hypertrophic response of skeletal muscle (increased skeletal muscle weight/protein synthesis efficiency and activation of mechanistic target of rapamycin complex 1 signaling) associated with mechanical overload was significantly suppressed during cancer cachexia. Screening of gene expression profile and pathway analysis using microarray revealed that blunted muscle protein synthesis was associated with cancer cachexia and was likely induced by downregulation of insulin-like growth factor-1 (IGF-1) and impaired activation of IGF-1-dependent signaling. CONCLUSIONS: These observations indicate that cancer cachexia induces resistance to muscle protein synthesis, which may be a factor for inhibiting the anabolic adaptation of skeletal muscle to physical exercise in cancer patients.

Modified thoracoabdominal nerve block through perichondrial approach (M-TAPA): an anatomical study to evaluate the spread of dye after a simulated injection in soft embalmed Thiel cadavers.

BACKGROUND AND OBJECTIVES: There is still no consensus on the analgesic range and mechanisms of action of modified thoracoabdominal nerve block through perichondrial approach (M-TAPA). This cadaveric study aimed to determine the spread of an injectate following simulated M-TAPA. METHODS: Simulated M-TAPA injections (n=8) were administered on both sides of soft embalmed Thiel cadavers with 25 mL of a saline-soluble dye. Anatomic dissection was performed to document staining (deeply, faintly, or not stained) of the anterior cutaneous branches of the thoracoabdominal nerves and determine the extent of the injectate spread of the dye to the intercostal space in the thoracic cage following a simulated M-TAPA. RESULTS: The median (IQR) dermatome of the stained segmental nerve was T10 (T8-T11) and the median (IQR) number of stained segmental nerves was 3 (4-2). The T9, T10 and T11 segmental nerves were stained in 75%, 100% and 62.5% of simulated M-TAPA, respectively. Conversely, the T8 segmental nerve was stained in only 25% of simulated M-TAPA. No injectate spread of dye to the intercostal space in the thoracic cage was observed in eight simulated injections of M-TAPA. CONCLUSION: Our findings suggest that M-TAPA most likely involves the T9, T10 and T11 segmental nerves and that the local anesthetic may not spread to the intercostal space in the thoracic cage in M-TAPA. Further studies are required to confirm the precise mechanism of action and efficacy of M-TAPA in a large sample of human participants.

Endoscopic resection is feasible for high-grade dysplasia in patients with ulcerative colitis.

BACKGROUND: Endoscopic resection (ER) is feasible for treating well-circumscribed dysplasia in patients with ulcerative colitis (UC). However, long-term prognosis of ER for high-grade dysplasia (HGD) in patients with UC remains unclear. We aimed to evaluate the long-term prognoses of ER for HGD compared with low-grade dysplasia (LGD) and verify the feasibility of ER and follow-up with surveillance colonoscopy for HGD. METHODS: An observational, single-center retrospective study included 38 and 22 patients with LGD and HGD who were followed-up with surveillance colonoscopy after ER. We evaluated the cumulative incidence rate of metachronous HGD or colorectal cancer (CRC) and identified the characteristics of metachronous dysplasia. RESULTS: The median follow-up period was 56 months, and surveillance colonoscopies were performed 3.6 times (mean). The 5-year cumulative incidence rate of HGD/CRC was relatively high in HGD (24.6%) than in LGD (13.7%), but the difference was not significant (p = .16). In HGD cases, six metachronous dysplasia lesions (two LGD and four HGD) were detected 11.6-40.5 months after ER. However, these patients did not progress to CRC. All metachronous lesions were well-circumscribed and with no invisible dysplasia surrounding them; they were 'endoscopically resectable' lesions. Two of the four metachronous HGD lesions were treated endoscopically and two, by colectomy. No synchronous HGD or CRC was detected in the colectomy specimens. CONCLUSIONS: Our results suggest that ER and follow-up with surveillance colonoscopy is feasible in patients with HGD when histological complete resection is achieved.

Cervical esophageal adenocarcinoma of intestinal type in ectopic gastric mucosa.

A 45-year-old man underwent esophagogastroduodenoscopy because of symptoms of laryngopharyngeal discomfort. We found a protruded reddish lesion adjacent to the ectopic gastric mucosa (EGM) in the cervical esophagus, and a biopsy revealed that it was a tubular adenocarcinoma. We diagnosed the patient with intramucosal cancer and performed endoscopic submucosal dissection. Esophageal endoscopic submucosal dissection was performed under general anesthesia using a conventional procedure. The resected tumor measured 23 × 14 mm and was adjacent to the EGM. Histologically, the tumor cells showed moderately well-differentiated adenocarcinoma confined to the muscularis mucosa with no lymphovascular infiltration. Immunohistochemically, the tumor cells were positive for intestinal markers, namely MUC2 and CD10, and negative for gastric markers, namely MUC5AC and MUC6. The patient had no post-endoscopy submucosal dissection stenosis and remained disease-free without local recurrence. EGM of the cervical esophagus develops from the columnar epithelium during embryonic development. There are few reports on endoscopic submucosal dissection for mucosal cancer. Of these, immunostaining was performed in three cases. All were positive for MUC5AC and MUC6 and negative for MUC2 and CD10. Usually, EGM shows gastric type epithelium, but occasional cases with intestinal metaplasia, which show positivity for MUC2 and CD10, have been reported. Therefore, we consider this to be an extremely rare case of esophageal adenocarcinoma arising from intestinal metaplasia within the EGM.

Fast-tracking antibody maturation using a B cell-based display system.

Affinity maturation, an essential component of antibody engineering, is crucial for developing therapeutic antibodies. Cell display system coupled with somatic hypermutation (SHM) initiated by activation-induced cytidine deaminase (AID) is a commonly used technique for affinity maturation. AID introduces targeted DNA lesions into hotspots of immunoglobulin (Ig) gene loci followed by erroneous DNA repair, leading to biased mutations in the complementary determining regions. However, systems that use an in vivo mimicking mechanism often require several rounds of selection to enrich clones possessing accumulated mutations. We previously described the human ADLib® system, which features autonomous, AID-mediated diversification in Ig gene loci of a chicken B cell line DT40 and streamlines human antibody generation and optimization in one integrated platform. In this study, we further engineered DT40 capable of receiving exogenous antibody genes and examined whether the antibody could be affinity matured. The Ig genes of three representative anti-hVEGF-A antibodies originating from the human ADLib® were introduced; the resulting human IgG1 antibodies had up to 76.4-fold improvement in binding affinities (sub-picomolar KD) within just one round of optimization, owing to efficient accumulation of functional mutations. Moreover, we successfully improved the affinity of a mouse hybridoma-derived anti-hCDCP1 antibody using the engineered DT40, and the observed mutations remained effective in the post-humanized antibody as exhibited by an 8.2-fold increase of in vitro cytotoxicity without compromised physical stability. These results demonstrated the versatility of the novel B cell-based affinity maturation system as an easy-to-use antibody optimization tool regardless of the species of origin.Abbreviations: ADLib®: Autonomously diversifying library, ADLib® KI-AMP: ADLib® knock-in affinity maturation platform, AID: activation-induced cytidine deaminase, CDRs: complementary-determining regions, DIVAC: diversification activator, ECD: extracellular domain, FACS: fluorescence-activated cell sorting, FCM: flow cytometry, HC: heavy chainIg: immunoglobulin, LC: light chain, NGS: next-generation sequencing, PBD: pyrrolobenzodiazepine, SHM: somatic hypermutation, SPR: surface plasmon resonance.

Learning curve analysis for duodenal endoscopic submucosal dissection: A single-operator experience.

BACKGROUND AND AIMS: Superficial duodenal epithelial tumors are emerging targets for endoscopic submucosal dissection (ESD). However, it is unknown how competence is achieved in duodenal ESD. This study aimed to elucidate the learning curve for duodenal ESD. METHODS: This retrospective observational study included 100 consecutive patients who underwent duodenal ESD by a single endoscopist between March 2014 and September 2021. The primary outcome was to define the learning curve for duodenal ESD by an endoscopist with sufficient non-duodenal ESD experience. Cumulative sum (CUSUM) curve analysis was used to assess the learning curve in terms of procedural speed. Comparative analyses of phases identified using the CUSUM method were performed. RESULTS: In total, 98 patients were included in the analysis. Evaluation of the cumulative sum curve revealed four distinct phases in the graph: phase I, cases 1-25 (learning phase); phase II, cases 26-47 (proficiency phase); phase III, cases 48-72 (mastery phase); and phase IV, cases 73-98 (after introduction of general anesthesia). The median procedural speed was significantly faster in phase II than in phase I (11.1 mm2 /min vs 7.0 mm2 /min, P = .002). Clinically significant intraoperative perforation tended to decrease through phase II to phase IV (22.7%, 12.0%, and 3.8% in phases II, III, and IV, respectively). Delayed perforation occurred only in phases I and II. CONCLUSIONS: Duodenal ESD requires 25 cases to gain proficiency and 50 to achieve mastery even for an endoscopist with extensive non-duodenal ESD experience.

Subpial delivery of adeno-associated virus 9-synapsin-caveolin-1 (AAV9-SynCav1) preserves motor neuron and neuromuscular junction morphology, motor function, delays disease onset, and extends survival in hSOD1G93A mice.

Elevating neuroprotective proteins using adeno-associated virus (AAV)-mediated gene delivery shows great promise in combating devastating neurodegenerative diseases. Amyotrophic lateral sclerosis (ALS) is one such disease resulting from loss of upper and lower motor neurons (MNs) with 90-95% of cases sporadic (SALS) in nature. Due to the unknown etiology of SALS, interventions that afford neuronal protection and preservation are urgently needed. Caveolin-1 (Cav-1), a membrane/lipid rafts (MLRs) scaffolding and neuroprotective protein, and MLR-associated signaling components are decreased in degenerating neurons in postmortem human brains. We previously showed that, when crossing our SynCav1 transgenic mouse (TG) with the mutant human superoxide dismutase 1 (hSOD1G93A) mouse model of ALS, the double transgenic mouse (SynCav1 TG/hSOD1G93A) exhibited better motor function and longer survival. The objective of the current study was to test whether neuron-targeted Cav-1 upregulation in the spinal cord using AAV9-SynCav1 could improve motor function and extend longevity in mutant humanized mouse and rat (hSOD1G93A) models of familial (F)ALS. Methods: Motor function was assessed by voluntary running wheel (RW) in mice and forelimb grip strength (GS) and motor evoked potentials (MEP) in rats. Immunofluorescence (IF) microscopy for choline acetyltransferase (ChAT) was used to assess MN morphology. Neuromuscular junctions (NMJs) were measured by bungarotoxin-a (Btx-a) and synaptophysin IF. Body weight (BW) was measured weekly, and the survival curve was determined by Kaplan-Meier analysis. Results: Following subpial gene delivery to the lumbar spinal cord, male and female hSOD1G93A mice treated with SynCav1 exhibited delayed disease onset, greater running-wheel performance, preserved spinal alpha-motor neuron morphology and NMJ integrity, and 10% increased longevity, independent of affecting expression of the mutant hSOD1G93A protein. Cervical subpial SynCav1 delivery to hSOD1G93A rats preserved forelimb GS and MEPs in the brachial and gastrocnemius muscles. Conclusion: In summary, subpial delivery of SynCav1 protects and preserves spinal motor neurons, and extends longevity in a familial mouse model of ALS without reducing the toxic monogenic component. Furthermore, subpial SynCav1 delivery preserved neuromuscular function in a rat model of FALS. The latter findings strongly indicate the therapeutic applicability of SynCav1 to treat ALS attributed to monogenic (FALS) and potentially in sporadic cases (i.e., SALS).

Magnifying endoscopy is useful for tumor border diagnosis in ulcerative colitis patients.

BACKGROUND AND AIMS: Endoscopic resection (ER) is feasible for well-circumscribed tumors in patients with ulcerative colitis (UC); however, the specific manner for diagnosis of the tumor border is unclear. We evaluated the efficacy of magnifying endoscopy (ME) for the diagnosis of tumor borders in UC. METHODS: We analyzed endoscopically or surgically resected tumors in UC patients in whom both chromoendoscopy (CE) and ME were performed, retrospectively. We classified the tumors based on tumor border visibility and evaluated tumor's characteristics and ER outcomes. RESULTS: We examined 100 tumors from 76 UC patients (66 distinct and 34 indistinct on CE). In 22 (65%) indistinct tumors on CE, ME improved the tumor border visibility. Compared with distinct tumors on CE, nonpolypoid and large tumors were more common in indistinct tumors on CE. In indistinct tumors even on ME, flat or depressed morphologies and type V pit were more frequently than in other groups. Sixty-five distinct tumors on CE and 18 distinct tumors on ME alone were treated endoscopically, and their R0 resection rate were 91% and 95% (p > 0.99). CONCLUSIONS: ME can improve the tumor border visibility in UC, and ER is feasible for tumors whose border can be visualized on ME.

Injectate spread in ultrasound-guided inferior alveolar nerve block: a cadaveric study.

PURPOSE: Ultrasound-guided inferior alveolar nerve block (UGIANB) is a mandibular analgesic procedure in which local anesthetic is injected into the pterygomandibular space (PMS). Several studies have reported the clinical efficacy of UGIANB for mandibular surgeries; however, its effective range has never been investigated. We performed a cadaveric study to investigate the success rate of UGIANB injections and to determine whether injected dye could stain the mandibular nerve (MN) trunk and its branches. METHODS: We performed UGIANB on the bilateral faces of 4 Thiel-embalmed cadavers. A needle was advanced to the PMS under ultrasound guidance and 5 mL of dye was injected. The cadaver was dissected and inspected for the presence of dye in the PMS; the range of dye spread to any of the inferior alveolar nerve (IAN), lingual nerve (LN), buccal nerve (BN), mandibular nerve (MN), auriculotemporal nerve (ATN), or facial nerves; and for the presence of intravascular dye. RESULTS: We performed eight UGIANB procedures on four cadavers. Dye was observed in the PMS in 7/8 injections. Staining was observed in all IAN, LN, and BNs that could be identified at dissection. No MN or auriculotemporal nerves (ATNs) were stained in any injections. No intravascular dye was observed in any injections. CONCLUSIONS: UGIANB can administer anesthetic into the PMS with high accuracy. UGIANB injections reached the IAN, LN, and BNs, but did not reach the MN or ATNs located outside the PMS. The findings of this cadaveric study indicate that UGIANB can provide sufficient analgesia for mandibular surgeries.

Dexmedetomidine Ameliorates Perioperative Neurocognitive Disorders by Suppressing Monocyte-Derived Macrophages in Mice With Preexisting Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) initiates immune responses involving infiltration of monocyte-derived macrophages (MDMs) in the injured brain tissue. These MDMs play a key role in perioperative neurocognitive disorders (PNDs). We tested the hypothesis that preanesthetic treatment with dexmedetomidine (DEX) could suppress infiltration of MDMs into the hippocampus of TBI model mice, ameliorating PND. METHODS: We first performed bone marrow transplantation from green fluorescent protein-transgenic mice to C57BL/6 mice to identify MDMs. We used only male mice for homogeneity. Four weeks after transplantation, a controlled cortical impact model of TBI was created using recipient mice. Four weeks after TBI, mice received pretreatment with DEX before general anesthesia (GA). Mice performed the Barnes maze test (8-12 mice/group) 2 weeks after GA and were euthanized for immunohistochemistry (4-5 mice/group) or immunoblotting (7 mice/group) 4 weeks after GA. RESULTS: In Barnes maze tests, TBI model mice showed longer primary latency (mean difference, 76.5 [95% confidence interval, 41.4-111.6], P < .0001 versus Naïve), primary path length (431.2 [98.5-763.9], P = .001 versus Naïve), and more primary errors (5.7 [0.62-10.7], P = .017 versus Naïve) than Naïve mice on experimental day 3. Expression of MDMs in the hippocampus was significantly increased in TBI mice compared to Naïve mice (2.1 [0.6-3.7], P = .003 versus Naïve). Expression of monocyte chemotactic protein-1 (MCP1)-positive areas in the hippocampus was significantly increased in TBI mice compared to Naïve mice (0.38 [0.09-0.68], P = .007 versus Naïve). Immunoblotting indicated significantly increased expression of interleukin-1ß in the hippocampus in TBI mice compared to Naïve mice (1.59 [0.08-3.1], P = .035 versus Naïve). In contrast, TBI mice pretreated with DEX were rescued from these changes and showed no significant difference from Naïve mice. Yohimbine, an α2 receptor antagonist, mitigated the effects of DEX (primary latency: 68.3 [36.5-100.1], P < .0001 versus TBI-DEX; primary path length: 414.9 [120.0-709.9], P = .0002 versus DEX; primary errors: 6.6 [2.1-11.2], P = .0005 versus TBI-DEX; expression of MDMs: 2.9 [1.4-4.4], P = .0001 versus TBI-DEX; expression of MCP1: 0.4 [0.05-0.67], P = .017 versus TBI-DEX; expression of interleukin-1ß: 1.8 [0.34-3.35], P = .01 versus TBI-DEX). CONCLUSIONS: Preanesthetic treatment with DEX suppressed infiltration of MDMs in the hippocampus and ameliorated PND in TBI model mice. Preanesthetic treatment with DEX appears to suppress infiltration of MDMs in the hippocampus and may lead to new treatments for PND in patients with a history of TBI.

Potential roles of gastroesophageal reflux in patients with superficial esophageal squamous cell carcinoma without major causative risk factors.

BACKGROUND: Cigarette smoking, alcohol consumption, and Lugol-voiding lesions (LVLs) are the major causative risk factors of esophageal squamous cell carcinoma (ESCC); however, reports on ESCC cases unrelated to these risk factors are very limited. Here, we investigated the clinicopathological features and etiology of such cases. METHODS: We retrospectively analyzed 704 consecutive superficial ESCC tumors of 512 patients who were treated with endoscopic submucosal dissection. The enrolled patients were divided into two groups-the very low-risk (VLR)-group and risk (R)-group-based on the presence of the abovementioned risks. Clinical, endoscopic, and pathological characteristics and genetic findings were assessed in both groups. RESULTS: The VLR-group consisted of 21 (4.1%) patients, who were characteristically female. Patients in the VLR-group presented gastroesophageal reflux disease (GERD), hiatal hernia, and non-open-type atrophic gastritis, and were negative for Helicobacter pylori. We found unique endoscopic features-frequently observed in the posterior wall of the middle thoracic esophagus-with a linear shape that closely resembled the erosion-like form of GERD. Additionally, histopathological examination showed that these tumors presented atypical nuclei limited to the basal and parabasal layer, sequential to the surrounding changes that presented pathological chronic inflammation of esophagitis. Evaluation of somatic mutations in cancer-related genes using next-generation sequencing revealed that the positive carcinogenic potential (TP53 mutation) of the tumors was relatively frequent in the VLR-group. CONCLUSIONS: Our study suggests that ESCC without major causative factors is related to GERD, with no remarkable oncogenic difference.