C-Reactive Protein/Albumin Ratio Is an Independent Risk Factor for Recurrence and Survival Following Curative Resection of Stage I-III Colorectal Cancer in Older Patients.

BACKGROUND: The number of older patients with cancer has increased, and colorectal cancer is expected to be affected by this trend. This study aimed to compare prognostic factors, including nutritional and inflammation-based indices, between patients aged ≥ 70 and < 70 years following curative resection of stage I-III colorectal cancer. PATIENTS AND METHODS: This study included 560 patients with stage I-III colorectal cancer who underwent curative resection between May 2010 and June 2018. A retrospective analysis was performed to identify prognosis-associated variables in patients aged ≥ 70 and < 70 years. RESULTS: Preoperative low body mass index, high C-reactive protein/albumin ratio, and comorbidities were mainly associated with poor prognosis in patients aged ≥ 70 years. Tumor factors were associated with a poor prognosis in patients aged < 70 years. The C-reactive protein/albumin ratio was independently associated with poor overall survival and recurrence-free survival in those aged ≥ 70 years. The time-dependent area under the curve for the C-reactive protein/albumin ratio was superior to those of other nutritional and inflammation-based indices in most postoperative observation periods in patients aged ≥ 70 years. CONCLUSIONS: Tumor factors were associated with a poor prognosis in patients aged < 70 years. In addition to lymph node metastasis, preoperative statuses were associated with poor prognosis in patients aged ≥ 70 years. Specifically, the preoperative C-reactive protein/albumin ratio was independently associated with long-term prognosis in patients aged ≥ 70 years with stage I-III colorectal cancer after curative resection.

Diagnostic performance and safety of endoscopic ultrasound-guided fine-needle aspiration/biopsy for gallbladder lesions.

OBJECTIVES: Endoscopic ultrasound-guided fine-needle aspiration and fine-needle biopsy (EUS-FNA/FNB) is not fully established as a pathological sampling tool for gallbladder lesions due to limited evidence. We therefore aimed to clarify the effectiveness and safety of this procedure in a large-population cohort. METHODS: This study retrospectively evaluated the diagnostic yield of EUS-FNA/FNB for accurately differentiating between benign and malignant gallbladder lesions. Puncture targets included the gallbladder mass, lymph node, and liver mass. Adverse events and factors associated with diagnostic accuracy were analyzed as well. RESULTS: In 187 patients with gallbladder lesions undergoing EUS-FNA/FNB, 18 benign lesions and 169 malignant lesions were identified. Overall sampling adequacy was 98% (184/187). The diagnostic accuracy of EUS-FNA/FNB was 97% (182/187), sensitivity was 97% (164/169), and specificity was 100% (18/18). A single postprocedural complication (minor bleeding) was recorded in one patient. In the 169 cases of malignancy, 203 sites were punctured for pathological sampling of the primary mass (n = 94), lymph node (n = 79), and metastatic liver mass (n = 30). No significant difference was found for diagnostic accuracy among the puncture sites (P = 0.70). In cases having specimens obtained from the primary mass, the accuracy of those targeting liver invasion sites was significantly higher than that of other sites (98% vs. 83%, P < 0.01). CONCLUSION: EUS-FNA/FNB demonstrated clinical usefulness and safety for the pathological diagnosis of gallbladder lesions, with high diagnostic yield and a low incidence of adverse events. Targeting the site of liver infiltration may improve the diagnostic rate of EUS-FNA/FNB in the primary mass.

Artificial intelligence using deep learning analysis of endoscopic ultrasonography images for the differential diagnosis of pancreatic masses.

BACKGROUND : There are several types of pancreatic mass, so it is important to distinguish between them before treatment. Artificial intelligence (AI) is a mathematical technique that automates learning and recognition of data patterns. This study aimed to investigate the efficacy of our AI model using endoscopic ultrasonography (EUS) images of multiple types of pancreatic mass (pancreatic ductal adenocarcinoma [PDAC], pancreatic adenosquamous carcinoma [PASC], acinar cell carcinoma [ACC], metastatic pancreatic tumor [MPT], neuroendocrine carcinoma [NEC], neuroendocrine tumor [NET], solid pseudopapillary neoplasm [SPN], chronic pancreatitis, and autoimmune pancreatitis [AIP]). METHODS : Patients who underwent EUS were included in this retrospective study. The included patients were divided into training, validation, and test cohorts. Using these cohorts, an AI model that can distinguish pancreatic carcinomas from noncarcinomatous pancreatic lesions was developed using a deep-learning architecture and the diagnostic performance of the AI model was evaluated. RESULTS : 22 000 images were generated from 933 patients. The area under the curve, sensitivity, specificity, and accuracy (95 %CI) of the AI model for the diagnosis of pancreatic carcinomas in the test cohort were 0.90 (0.84-0.97), 0.94 (0.88-0.98), 0.82 (0.68-0.92), and 0.91 (0.85-0.95), respectively. The per-category sensitivities (95 %CI) of each disease were PDAC 0.96 (0.90-0.99), PASC 1.00 (0.05-1.00), ACC 1.00 (0.22-1.00), MPT 0.33 (0.01-0.91), NEC 1.00 (0.22-1.00), NET 0.93 (0.66-1.00), SPN 1.00 (0.22-1.00), chronic pancreatitis 0.78 (0.52-0.94), and AIP 0.73 (0.39-0.94). CONCLUSIONS : Our developed AI model can distinguish pancreatic carcinomas from noncarcinomatous pancreatic lesions, but external validation is needed.

Novel drill dilator facilitates endoscopic ultrasound-guided hepaticogastrostomy.

Tract dilation is one of the most difficult stages of endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS), especially for beginners. To overcome this problem, we applied a special dedicated dilator. Herein, we retrospectively evaluate the safety and usefulness of a novel drill dilator in EUS-HGS. This single-center retrospective study included 20 consecutive patients who underwent EUS-HGS with a novel drill dilator. The tip is 0.77 mm, and it becomes 7F at 3 cm from tip. The track is dilated to 7F by simple clockwise rotation. The technical success rate of both initial tract dilation and stent placement was 20/20 (100%). No cases required additional dilation such as balloon or electric cautery. In 13/20 cases (65.0%), EUS-HGS was performed by beginner endoscopists. Median time required for dilation was 62.5 s (range, 30-144 s). Median procedure time was 13 min (range, 7-25 min). Early adverse events were two cases of mild fever. There was no bile leakage or bleeding. The novel drill dilator appears to be safe and useful for EUS-HGS. As it is not necessary to press the device strongly, there is no pushback during dilation and the scope position is stable. These characteristics facilitate EUS-HGS even for beginners. This device may enable the further development and increased dissemination of EUS intervention.

Metagenomic Shotgun Sequencing Analysis of Canalicular Concretions in Lacrimal Canaliculitis Cases.

Lacrimal canaliculitis is a rare infection of the lacrimal canaliculi with canalicular concretions formed by aggregation of organisms. Metagenomic shotgun sequencing analysis using next-generation sequencing has been used to detect pathogens directly from clinical samples. Using this technology, we report cases of successful pathogen detection of canalicular concretions in lacrimal canaliculitis cases. We investigated patients with primary lacrimal canaliculitis examined in the eye clinics of four hospitals from February 2015 to July 2017. Eighteen canalicular concretion specimens collected from 18 eyes of 17 patients were analyzed by shotgun metagenomics sequencing using the MiSeq platform (Illumina). Taxonomic classification was performed using the GenBank NT database. The canalicular concretion diversity was characterized using the Shannon diversity index. This study included 18 eyes (17 patients, 77.1 ± 6.1 years): 82.4% were women with lacrimal canaliculitis; canalicular concretions were obtained from 12 eyes using lacrimal endoscopy and six eyes using canaliculotomy with curettage. Sequencing analysis detected bacteria in all samples (Shannon diversity index, 0.05-1.47). The following genera of anaerobic bacteria (>1% abundance) were identified: Actinomyces spp. in 15 eyes, Propionibacterium spp., Parvimonas spp. in 11 eyes, Prevotella spp. in 9 eyes, Fusobacterium spp. in 6 eyes, Selenomonas spp. in 5 eyes, Aggregatibacter spp. in 3 eyes, facultative and aerobic bacteria such as Streptococcus spp. in 13 eyes, Campylobacter spp. in 6 eyes, and Haemophilus spp. in 3 eyes. The most common combinations were Actinomyces spp. and Streptococcus spp. and Parvinomonas spp. and Streptococcus spp., found in 10 cases. Pathogens were identified successfully using metagenomic shotgun sequencing analysis in patients with canalicular concretions. Canalicular concretions are polymicrobial with anaerobic and facultative, aerobic bacteria.

Efficacy and safety of cold forceps biopsy for diminutive pharyngeal neoplasms: Single-center, prospective pilot study.

BACKGROUND: Management of diminutive pharyngeal neoplasms is controversial. Thus, we conducted a single-center, prospective pilot study to investigate the efficacy and safety of endoscopic excision with cold forceps biopsy (CFB) of these lesions. PATIENTS AND METHODS: Thirty-nine lesions endoscopically diagnosed with narrow-band imaging as pharyngeal neoplasms of 3 mm or smaller were excised with CFB using jumbo biopsy forceps (cap diameter 2.8 mm, jaw volume 12.4 mm3 ). The primary outcome was endoscopically determined local remnant/recurrence rate 3 months after CFB. The secondary outcomes were histopathologically determined local remnant/recurrence rate; risk factors associated with the endoscopic remnant/recurrence; and incidence of intraoperative or delayed bleeding and other adverse events. RESULTS: Histological diagnosis of the 39 CFB-excised lesions were: 11 high-grade dysplasia (28.2%), 22 low-grade dysplasia (56.4%), two basal cell hyperplasia (5.1%) and four atypical squamous epithelium (10.3%).Twenty-seven patients (30 lesions) underwent follow-up endoscopy 3 months after CFB; the endoscopic and pathological local remnant/recurrence rate was 20% (6/30; 95% confidence interval (CI), 7.7-36.6%) and 16.7% (5/30; 95% CI, 5.6-34.7%), respectively. Location of the lesion in the hypopharynx was a significant risk factor associated with the endoscopic local remnant/recurrence (P = 0.049). No significant adverse events occurred. CONCLUSIONS: Cold forceps biopsy with jumbo biopsy forceps appears to be a safe and effective technique for excising diminutive pharyngeal neoplasms. Although small, the excised lesions may have a remarkably high frequency of high-grade dysplasia. (Clinical trial registration number: UMIN000037980).

Development of Chiral Ureates as Chiral Strong Brønsted Base Catalysts.

Recently, chiral Brønsted bases having high basicity have emerged as a powerful tool in developing new catalytic enantioselective reactions. However, such chiral strong Brønsted base catalysts are still very scarce. Herein, we report the development of a chiral anionic Brønsted base having a N,N'-dialkyl ureate moiety as a basic site. Its prominent catalytic activity was demonstrated in the enantioselective addition reactions of α-thioacetamides as less acidic pronucleophiles with various electrophiles. Thus, the newly developed chiral catalyst with high accessibility and structural tunability would expand the scope of viable enantioselective transformations under Brønsted base catalysis.

Enantioselective hydrophosphinylation of 1-alkenylphosphine oxides catalyzed by chiral strong Brønsted base.

A catalytic enantioselective addition of diarylphosphine oxides to 1-alkenyl(diaryl)phosphine oxides was achieved by using a chiral ureate as a chiral strong Brønsted base catalyst. The reaction followed by the reduction of phosphine oxide moieties provided chiral 1,2-diphosphinoalkanes, which are a family of useful chiral ligands for asymmetric transition metal catalysis.

Efficient Synthesis of Polysubstituted Pyrroles Based on [3+2] Cycloaddition Strategy Utilizing [1,2]-Phospha-Brook Rearrangement under Brønsted Base Catalysis.

An efficient method for the synthesis of polysubstituted pyrroles was established based on the [3+2] cycloaddition strategy utilizing the [1,2]-phospha-Brook rearrangement under Brønsted base catalysis. The less-explored approach of the [3+2] cycloaddition, that is, the reaction of a C3 subunit with imines, was successfully achieved by making use of newly designed C3 subunits containing the requisite umpolung. The two-step formal [3+2] cycloaddition involves the catalytic generation of an α-oxygenated propargyl anion through the [1,2]-phospha-Brook rearrangement followed by γ-addition to the imine under Brønsted base catalysis and the subsequent intramolecular cyclization mediated by Au catalyst or a halogenation reagent to afford polysubstituted pyrroles having a variety of substituents in a positional selective manner. The pyrroles thus synthesized were amenable to further transformations, such as palladium-catalyzed cross-coupling reactions. The operationally very simple method with readily available substrates provides new access to a diverse array of well-organized polysubstituted pyrroles.

Quantitative evaluation of corneal epithelial edema after cataract surgery using corneal densitometry: a prospective study.

PURPOSE: The optical density of the cornea can be evaluated quantitatively by "densitometry" using a rotating Scheimpflug camera. Densitometry allows evaluation of corneal opacity in the anterior segment of the eye by quantitative measurement of scattering light. In the present investigation, we evaluate quantitatively minimal subclinical corneal edema after cataract surgery using densitometry. METHODS: Fifty four eyes of 34 patients who underwent cataract surgery were enrolled. Measurement of corneal density was performed using Pentacam® before and on days 1, 3 and 7 after surgery. RESULTS: Densitometry scores increased from 18.12 ± 1.76 before cataract surgery to 21.03 ± 3.84 on day 1 (P < 0.001) and 19.90 ± 2.46 on day 3 (P = 0.018), but recovered to 19.44 ± 1.58 on day 7 (P = 0.131). Total corneal thickness was 549.1 ± 32.7 µm before surgery and increased to 582.7 ± 46.3 µm on day 1 (P = 0.001), but recovered to 566.4 ± 29.7 µm on day 3 (P = 0.097). Densitometry reading correlated positively with corneal thickness (correlation coefficient = 0.13, P = 0.003). CONCLUSIONS: Densitometry is useful to detect corneal edema that is not detectable by slit-lamp examination.

The Core Molecular Machinery Used for Engulfment of Apoptotic Cells Regulates the JNK Pathway Mediating Axon Regeneration in Caenorhabditis elegans.

UNLABELLED: The mechanisms that govern the ability of specific neurons to regenerate their axons after injury are not well understood. In Caenorhabditis elegans, the initiation of axon regeneration is positively regulated by the JNK-MAPK pathway. In this study, we identify two components functioning upstream of the JNK pathway: the Ste20-related protein kinase MAX-2 and the Rac-type GTPase CED-10. CED-10, when bound by GTP, interacts with MAX-2 and functions as its upstream regulator in axon regeneration. CED-10, in turn, is activated by axon injury via signals initiated from the integrin α-subunit INA-1 and the nonreceptor tyrosine kinase SRC-1 and transmitted via the signaling module CED-2/CrkII-CED-5/Dock180-CED-12/ELMO. This module is also known to regulate the engulfment of apoptotic cells during development. Our findings thus reveal that the molecular machinery used for engulfment of apoptotic cells also promotes axon regeneration through activation of the JNK pathway. SIGNIFICANCE STATEMENT: The molecular mechanisms of axon regeneration after injury remain poorly understood. In Caenorhabditis elegans, the initiation of axon regeneration is positively regulated by the JNK-MAPK pathway. In this study, we show that integrin, Rac-GTPase, and several other molecules, all of which are known to regulate engulfment of apoptotic cells during development, also regulate axon regeneration. This signaling module activates the JNK-MAPK cascade via MAX-2, a PAK-like protein kinase that binds Rac. Our findings thus reveal that the molecular machinery used for engulfment of apoptotic cells also promotes axon regeneration through activation of the JNK pathway.

Comparison between Outcomes of Vitrectomy in Granulomatous and Nongranulomatous Uveitis.

PURPOSE: The aim of this study was to compare the outcomes of vitrectomy in granulomatous uveitis and nongranulomatous uveitis insufficiently managed by immunosuppressive therapy. METHODS: Thirty-eight eyes with granulomatous uveitis and 17 eyes with nongranulomatous uveitis that underwent vitrectomy for ocular complications between July 2006 and August 2012 were reviewed retrospectively. Visual acuity and ocular inflammation scores before and 6 months after surgery were compared. Patients treated with vitrectomy alone and those in whom vitrectomy was combined with phacoemulsification were analyzed separately. RESULTS: The mean visual acuity improved significantly both in granulomatous and nongranulomatous uveitis. In granulomatous uveitis, the mean inflammation scores decreased significantly both in the anterior segment and in the posterior segment. In nongranulomatous uveitis, the mean inflammation score in the posterior segment decreased significantly, although it did not change in the anterior segment. CONCLUSION: Vitrectomy was effective for treating ocular complications both in granulomatous uveitis and nongranulomatous uveitis, with favorable outcomes of improved visual acuity and decreased uveitis activity.

Short-term outcomes of coaxial microincision cataract surgery for uveitis-associated cataract without postoperative systemic steroid therapy.

PURPOSE: To study the necessity of prophylactic systemic steroid therapy after coaxial microincision cataract surgery (MICS) conducted in aged patients during remission of uveitis. PROCEDURES: A total of 17 consecutive patients who underwent MICS were enrolled in this retrospective study. The median age was 73 years. MICS via a 2.2-mm incision was performed. None of the patients received systemic steroid administration after surgery. The visual acuity, intraocular pressure (IOP) and inflammation scores were recorded. RESULTS: The mean logMAR visual acuity was significantly improved from 0.56 ± 0.58 to 0.10 ± 0.30, and the mean inflammation score was reduced from 0.20 to 0.14. Postoperative complications were recurrence of ocular inflammation in 1 eye and elevation of IOP more than 21 mm Hg in 1 eye, which were resolved by topical steroids and topical antiglaucoma medication. CONCLUSIONS: Prophylactic systemic steroid therapy after MICS may not be necessary in aged uveitis patients without posterior complications before cataract surgery.

Construction of 1,3-Nonadjacent Stereogenic Centers Through Enantioselective Addition of α-Thioacetamides to α-Substituted Vinyl Sulfones Catalyzed by Chiral Strong Brønsted Base.

An enantioselective addition reaction for the construction of 1,3-nonadjacent stereogenic centers is developed by means of a chiral strong Brønsted base catalyst. The chiral sodium ureate catalyst efficiently promoted the reaction of α-thioacetamides as less acidic pronucleophiles with vinyl sulfones having a variety of α-substituents including aryl, alkyl and halo groups, and α-phenylacrylates, accomplishing the construction of various 1,3-nonadjacent stereogenic centers in highly diastereo- and enantioselective manners. This is a rare example of the construction of 1,3-nonadjacent stereogenic centers with less acidic pronucleophiles. In addition, the application of Michael acceptors having various types of α-substituents in a single catalyst system is achieved for the first time, demonstrating the utility of the present catalyst system for the construction of 1,3-nonadjacent stereogenic centers.

Refractory benign biliary stricture due to chronic pancreatitis in two patients treated using endoscopic ultrasound-guided choledochoduodenostomy fistula creation: case reports.

Benign biliary stricture (BBS) is a complication of chronic pancreatitis (CP). Despite endoscopic biliary stenting, some patients do not respond to treatment, and they experience recurrent cholangitis. We report two cases of CP with refractory BBS treated using endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) fistula creation. A 50-year-old woman and a 60-year-old man both presented with obstructive jaundice secondary to BBS due to alcoholic CP. They underwent repeated placement of a fully covered self-expandable metal stent for biliary strictures. However, the strictures persisted, causing repeated episodes of cholangitis. Therefore, an EUS-CDS was performed. The stents were eventually removed and the patients became stent-free. These fistulas have remained patent without cholangitis for more than 2.5 years. Fistula creation using EUS-CDS is an effective treatment option for BBS.

Safety of endoscopic ultrasound-guided hepaticogastrostomy in patients with malignant biliary obstruction and ascites.

BACKGROUND/AIMS: Endoscopic ultrasound (EUS)-guided hepaticogastrostomy (EUS-HGS) is useful for patients with biliary cannulation failure or inaccessible papillae. However, it can lead to serious complications such as bile peritonitis in patients with ascites; therefore, development of a safe method to perform EUS-HGS is important. Herein, we evaluated the safety of EUS-HGS with continuous ascitic fluid drainage in patients with ascites. METHODS: Patients with moderate or severe ascites who underwent continuous ascites drainage, which was initiated before EUS-HGS and terminated after the procedure at our institution between April 2015 and December 2022, were included in the study. We evaluated the technical and clinical success rates, EUS-HGS-related complications, and feasibility of re-intervention. RESULTS: Ten patients underwent continuous ascites drainage, which was initiated before EUS-HGS and terminated after completion of the procedure. Median duration of ascites drainage before and after EUS-HGS was 2 and 4 days, respectively. Technical success with EUS-HGS was achieved in all 10 patients (100%). Clinical success with EUS-HGS was achieved in 9 of the 10 patients (90 %). No endoscopic complications such as bile peritonitis were observed. CONCLUSION: In patients with ascites, continuous ascites drainage, which is initiated before EUS-HGS and terminated after completion of the procedure, may prevent complications and allow safe performance of EUS-HGS.

Clinical utility of endoscopic ultrasound-guided tissue acquisition for comprehensive genomic profiling of patients with biliary tract cancer, especially with intrahepatic cholangiocarcinoma.

BACKGROUND/AIMS: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is a standard diagnostic method for biliary tract cancer (BTC), and samples obtained in this manner may be used for comprehensive genomic profiling (CGP). This study evaluated the utility of EUS-TA for CGP in a clinical setting and determined the factors associated with the adequacy of CGP in patients with BTC. METHODS: CGP was attempted for 105 samples from 94 patients with BTC at the Aichi Cancer Center, Japan, from October 2019 to April 2022. RESULTS: Overall, 77.1% (81/105) of the samples were adequate for CGP. For 22-G or 19-G fine-needle biopsy (FNB), the sample adequacy was 85.7% (36/42), which was similar to that of surgical specimens (94%, p=0.45). Univariate analysis revealed that 22-G or larger FNB needle usage (86%, p=0.003), the target primary lesions (88%, p=0.015), a target size ≥30 mm (100%, p=0.0013), and number of punctures (90%, p=0.016) were significantly positively associated with CGP sample adequacy. CONCLUSIONS: EUS-TA is useful for CGP tissue sampling in patients with BTC. In particular, the use of 22-G or larger FNB needles may allow for specimen adequacy comparable to that of surgical specimens.

Pancreatic Pseudocyst after Fully Covered Self-expandable Metallic Stent Placement: A Case Report.

A 70-year-old woman presented with stage III pancreatic head cancer. After endoscopic sphincterotomy, a fully covered self-expandable metallic stent (FCSEMS) was placed in the common bile duct to manage jaundice. The patient developed a fever and abdominal pain 40 days after stent placement, with a suspected diagnosis of infected pancreatic pseudocyst. Purulent discharge from the papilla was observed during FCSEMS removal, and pancreatography revealed a pseudocyst connected to the main pancreatic duct. The pancreatic pseudocyst resolved after transpapillary drainage. Pancreatic pseudocysts should be suspected after biliary FCSEMS placement, and prompt removal and endoscopic drainage of the FCSEMS should be considered.

Safety and efficacy of novel oblique-viewing scope for B2-endoscopic ultrasound-guided hepaticogastrostomy.

BACKGROUND/AIMS: Endoscopic ultrasound (EUS)-guided hepaticogastrostomy (EUS-HGS) performed at the intrahepatic bile duct segment 3 (B3) is widely used for biliary drainage. Although performing post-puncture procedures is easier in the intrahepatic bile duct segment 2 (B2) when using a conventional oblique-viewing (OV) EUS scope, this method may cause transesophageal puncture and severe adverse events. We evaluated the safety and efficacy of B2 puncture using a novel OV-EUS scope. METHODS: In this single-center retrospective study, we prospectively enrolled and collected data from 45 patients who consecutively underwent EUS-HGS procedures with a novel OV-EUS scope between September 2021 and December 2022 at our cancer center. RESULTS: The technical success rates of B2-EUS-HGS and EUS-HGS were 93.3% (42/45) and 97.8% (44/45), respectively. The early adverse event rate was 8.9% (4/45) with no cases of scope changes or transesophageal punctures. The median procedure time was 13 minutes (range, 5-30). CONCLUSIONS: B2-EUS-HGS can be performed safely with the novel EG-740UT (Fujifilm) OV-scope without transesophageal puncture and with a high success rate. B2-EUS-HGS using this novel OV scope may be the preferred strategy for EUS-HGS.