Clinical usefulness and acceptability of small-bowel capsule endoscopy with panoramic imaging compared with axial imaging in Japanese patients.

Objectives: We aimed to evaluate the usefulness and acceptability of CapsoCam Plus (CapsoCam) in Japanese patients. Methods: This retrospective single-center study enrolled 930 patients with suspected small-bowel bleeding (SSBB) who underwent capsule endoscopy. Thirty-three patients using CapsoCam and PillCam SB3 (SB3) were matched using propensity score matching. The diagnostic yield and the acceptability of CapsoCam were evaluated. Results: There was no SSBB case where capsule endoscopy was performed within 48 h of bleeding. CapsoCam had a significantly higher observation rate of the entire small bowel (97% vs. 73%, p = 0.006) and Vater's papilla (82% vs. 15%, p < 0.001) than SB3. The reading time of CapsoCam was significantly longer than that of SB3 (30 vs. 25 min, p < 0.001), and CapsoCam's time from the capsule endoscopy swallowing to read completion was longer than that of SB3 (37 vs. 12 h, p < 0.001). The two groups showed no difference in the capsule endoscopy findings according to the P classification. Notably, 85% of the patients using CapsoCam reported examination distress as "not at all" or "almost not," and 94% reported swallowing difficulty as "very easy" or "easy." Conclusions: CapsoCam took time to read; however, it is a well-tolerated examination with a high observation rate of Vater's papilla and entire small-bowel mucosa. Detectability of bleeding sources was comparable in both modalities for cases of occult SSBB and overt SSBB more than 48 h after bleeding. CapsoCam is a useful modality for patients with SSBB.

Vertical margin distance in T1 colorectal carcinoma resected by endoscopic submucosal dissection affects prognosis after additional surgery.

PURPOSE : A vertical margin (VM) distance of < 500 µm is a risk factor for recurrence in patients with T1 colorectal carcinoma (CRC) resected by endoscopy. We aimed to determine the effects of the VM distance on the recurrence and prognosis of T1 CRC. METHODS: We enrolled 168 patients with T1 CRC who underwent additional surgery after endoscopic submucosal dissection (ESD) at multiple centers between 2008 and 2016. None of the patients were followed up for < 5 years. The enrolled 168 patients were classified into patients with VM distance of < 500 µm including positive VM (n = 72 [43%], VM distance < 500 µm group) and patients with VM distance of ≥ 500 µm (n = 96 [57%], VM distance ≥ 500 µm group). The clinicopathological features, recurrence rates, and prognoses were compared between the groups using propensity-score matching (PSM). RESULTS: Tumors recurred in eight of the 168 patients (5%) with VM distance < 500 µm. After PSM, the rate of overall recurrence and local recurrence in the VM distance < 500 µm group were significantly higher than those in the VM distance ≥ 500 µm group. The 5-year recurrence-free survival rate was significantly higher in the VM distance ≥ 500 µm group than that in VM distance < 500 µm group after PSM (100% vs. 89%, p < 0.012). CONCLUSIONS: Complete en bloc resection of T1 CRC via ESD must include a sufficient amount of SM to reduce the risk of metastasis and recurrence after additional surgery.

Genetic polymorphisms of calpain1 and calpain3 genes and their effects on growth, carcass, and meat quality traits in Betong chicken (KU line).

Betong chicken (KU line) is a slow-growing Thai native chicken used for meat production. The objectives of this study were to identify polymorphisms of the calpain1 (CAPN1) and calpain3 (CAPN3) genes and to investigate their effects on growth, carcass, and meat quality traits in Betong chickens (KU line). A sample of 252 Betong chickens (KU line) was screened for CAPN1 and CAPN3 polymorphisms. The polymorphisms of CAPN1 were detected using gel electrophoresis and DNA sequencing, whereas the polymorphisms of CAPN3 were identified using restriction fragment length polymorphism. Polymorphisms were detected in both CAPN1 (AA, AB, and BB genotypes) and CAPN3 (CC, CT, and TT genotypes). The frequency of the B allele was higher than for the A allele (0.78 and 0.22, respectively) in CAPN1, while the C allelic frequency was higher than for the T allele (0.54 and 0.46, respectively) in CAPN3. The CAPN1 genotype and the combination of the CAPN1 and CAPN3 genotypes could be used as genetic markers for meat lightness. The CAPN3 could be useful for increasing body weight, live weight, and breast meat weight in Betong chickens (KU line).

Sex Differences in Predicting Difficult Laryngeal Exposure: Validation and Modification of Predictive Models.

OBJECTIVES/HYPOTHESIS: To determine the presence of sex differences in difficult laryngeal exposure and the Laryngoscore, validate the Laryngoscore, mini-Laryngoscore, and Clarysse's model for predicting difficult laryngeal exposure, and modify the Laryngoscore for improved prediction accuracy. STUDY DESIGN: Retrospective study. METHODS: This study included 153 patients who underwent laryngeal microsurgery at a tertiary laryngology center and university hospital. Patients were evaluated using the 11 items of the Laryngoscore, mini-Laryngoscore, and Clarysse's model to predict difficult laryngeal exposure. Difficult laryngeal exposure was defined as the inability to view the anterior commissure through a rigid laryngoscope under counterpressure to the anterior neck. Descriptive statistics and receiver-operating characteristic curve analysis were used to assess the diagnostic performance of the predictive models and variables, including sex. RESULTS: The prevalence of difficult laryngeal exposure was significantly higher in men than in women, despite higher Laryngoscore values in females. The Laryngoscore, mini-Laryngoscore, and Clarysse's model demonstrated good diagnostic performance with C-indexes of 0.751, 0.727, and 0.783, respectively. Based on these findings, we proposed a modified Laryngoscore, including treatment history, interincisors gap, upper jaw dental status, thyro-mental distance, degree of neck flexion-extension, and sex, achieving a C-index of 0.835. CONCLUSIONS: Inclusion of sex in the Laryngoscore and related predictive models enhances the accuracy of predicting difficult laryngeal exposure. These findings support the inclusion of sex as a factor in future modifications of these models to improve their predictive performance.

Predictive factors of portal hypertensive enteropathy exacerbations based on long-term outcomes.

BACKGROUND: Portal hypertensive enteropathy (PHE) is a small-bowel lesion observed in patients with portal hypertension. The clinical significance of endoscopic findings in PHE remains unclear. We aimed to clarify the clinical significance and predictive factors of capsule endoscopic findings in patients with PHE based on long-term outcomes. METHODS: This retrospective study enrolled 55 patients with PHE (33 males and 22 females; median age, 64 years; range, 23-87) followed for > 3 years using capsule endoscopy (CE) between February 2009 and May 2023. We evaluated the clinical factors affecting PHE exacerbations and the effects of PHE exacerbations on gastrointestinal bleeding by comparing exacerbated and unchanged PHE groups. RESULTS: Overall, 3 (5%) patients showed improvement, 33 (60%) remained unchanged, and 19 (35%) showed exacerbation on follow-up CE. In the exacerbated group, the rates of worsened fibrosis-4 index, exacerbated esophageal varices, and exacerbated portal hypertensive gastropathy were significantly higher than those in the unchanged group (21%, 32%, and 42% vs. 3%, 6%, and 12%, respectively; P < 0.05), and the rate of splenectomy was significantly lower in the exacerbated group than in the unchanged group (5% vs. 39%, respectively; P < 0.01). In multivariate analysis, exacerbation of esophageal varices and absence of splenectomy were significantly associated with PHE exacerbation. The rate of gastrointestinal bleeding after follow-up CE was significantly high in the exacerbated group (log-rank, P = 0.037). CONCLUSIONS: Exacerbation of esophageal varices and splenectomy were significantly associated with exacerbation of PHE. Exacerbated PHE requires specific attention to prevent gastrointestinal bleeding.

Management of T1 Colorectal Cancer.

BACKGROUND: Approximately 10% of patients with submucosal invasive (T1) colorectal cancer (CRC) have lymph node metastasis (LNM). The risk of LNM can be stratified according to various histopathological factors, such as invasion depth, lymphovascular invasion, histological grade, and tumor budding. SUMMARY: T1 CRC with a low risk of LNM can be cured by local excision via endoscopic resection (ER), whereas surgical resection (SR) with lymph node dissection is required for high-risk T1 CRC. Current guidelines raise concern that many patients receive unnecessary SR, even though most patients achieve a radical cure. Novel diagnostic techniques for LNM, such as nomograms, artificial intelligence systems, and genomic analysis, have been recently developed to identify more low-risk T1 CRC cases. Assessing the curability and the necessity of additional treatment, including SR with lymph node dissection and chemoradiotherapy, according to histopathological findings of the specimens resected using ER, is becoming an acceptable strategy for T1 CRC, particularly for rectal cancer. Therefore, complete resection with negative vertical and horizontal margins is necessary for this strategy. Advanced ER methods for resecting the muscle layer or full thickness, which may guarantee complete resection with negative vertical margins, have been developed. KEY MESSAGE: Although a necessary SR should not be delayed for T1 CRC given its unfavorable prognosis when SR with lymph node dissection is performed, the optimal treatment method should be chosen based on the risk of LNM and the patient's life expectancy, physical condition, social characteristics, and wishes.

Severe Refractory Diarrhea Associated with COVID-19: A Case Report.

Introduction: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is frequently associated with various gastrointestinal symptoms, including abdominal pain, vomiting, and diarrhea. Moreover, several cases of refractory diarrhea have been reported after COVID-19 recovery. Herein, we present a case of severe refractory diarrhea associated with COVID-19. Case Presentation: A 50-year-old man with no comorbidities was admitted to our hospital with SARS-CoV-2 pneumonia. His respiratory status deteriorated, and ventilatory management, including extracorporeal membrane oxygenation, was needed. The patient's respiratory condition improved, resulting in a transfer to another hospital for rehabilitation. However, the patient developed diarrhea that worsened to 6,000-7,000 mL/day, and he was transferred to our hospital. We diagnosed the patient with enterocolitis caused by cytomegalovirus infection and treated him with ganciclovir on day 5 after transfer to our hospital. The diarrhea did not improve. We suspected enterocolitis associated with COVID-19 and administered a methylprednisolone pulse (intravenous injection, 1,000 mg/day for 3 days) on day 10 after transfer, resulting in a marked improvement in his symptoms. The prednisolone dose was tapered, and no recurrence of diarrhea was observed thereafter. Conclusion: The prevalence of COVID-19-associated enterocolitis is low, and the pathogenesis of the disease remains unclear. Prednisolone administration should be considered in cases of post-COVID-19 symptoms of severe diarrhea due to a possible abnormal immune response related to COVID-19.

Randomized controlled trial to examine the tolerability of bronchoscopy with and without pharyngeal laryngeal anesthesia (TACOYAKI study).

BACKGROUND: The SARS-CoV-2 pandemic, pharyngeal anesthesia such as nebulizer or lidocaine pump spray is the risk of droplet transmission to health care workers from coughing due to spraying anesthesia. Absence of pharyngeal anesthesia may induce coughing and reduce patient and operator satisfaction, but the efficacy of pharyngeal anesthesia under sedation is still limited. Therefore we evaluated a prospective, randomized, single-blind trial to evaluate efficacy of pharyngeal anesthesia in patients receiving sedation. MATERIALS AND METHODS: We conducted a randomized comparison of pharyngeal anesthesia with or without bronchoalveolar lavage in patients undergoing bronchoscopy at our hospital between March and October 2022. Pharyngeal anesthesia was performed using 8％ lidocaine spray and the operators were blinded to eliminate bias. Two hundred patients were entered into the study and divided into two groups: those who received pharyngeal anesthesia(control group) and did not receive pharyngeal anesthesia(test group). The primary endpoint was the operator's satisfaction with the procedure. The secondary endpoints were the patient's cough during the examination as perceived by the operator, cough and discomfort experienced by the patient and the dose of analgesic/sedative/lidocaine administered. These scales were scored from 0 to 100. RESULT: In primary endpoint, there was no significant difference in the operator-rated procedure satisfaction between the 2 groups. The median for the discomfort score for patients in the control group was tendency higher than in the test group. There were no significant differences in other secondary endpoints. CONCLUSION: Pharyngeal anesthesia may not be recommended for flexible bronchoscopy performed under combined sedation and analgesia. TRIAL REGISTRATION: Registration number: UMIN000046975Date of registration: 2022/03/07.

Survival of Metastatic Human Papillomavirus (HPV)-Related Head and Neck Cancer Receiving Platinum-Based Triplet Induction Chemotherapy and Relevance of Circulating Tumor HPV DNA.

Objectives We aimed to examine the effectiveness of platinum-based triplet induction chemotherapy in metastatic squamous cell carcinoma of the head and neck (HNSCC) at diagnosis in terms of tumor human papillomavirus (HPV) status and the clinical relevance of circulating tumor HPV DNA (ctHPVDNA) during induction chemotherapy. Methods  Twenty-one patients were included. ctHPVDNA was longitudinally quantified using optimized digital PCR in a subset of patients. Results HPV-related HNSCC patients (N=7) had a significantly better response to induction chemotherapy than HPV-unrelated HNSCC patients (N=14) (complete or partial response rate, 100% vs. 36%, P = 0.007). Following induction chemotherapy, more HPV-related HNSCC patients than HPV-unrelated patients received radiotherapy (86% vs. 36%, P = 0.06). With a median follow-up of 26 months in surviving patients, the two-year overall survival was 86% in HPV-related HNSCC patients and 43% in HPV-unrelated HNSCC patients (P = 0.04). In two patients, ctHPVDNA levels drastically decreased after the first cycle of induction chemotherapy but turned to continuous increase after the second cycle, suggesting the acquisition of drug resistance by the end of the second cycle. Radiographic imaging after induction chemotherapy failed to identify the drug resistance. In one patient, ctHPVDNA decreased gradually but remained detectable after induction chemotherapy despite no radiographic residual disease. ctHPVDNA became undetectable during radiotherapy. Conclusion HPV-related HNSCC patients with distant metastasis at diagnosis should be treated definitively. The ctHPVDNA level reflects real-time disease activity. ctHPVDNA monitoring during induction chemotherapy could help the decision-making of the therapeutic strategy.

Protecting-Group-Free Synthesis of ADP-Ribose and Dinucleoside Di-/Triphosphate Derivatives via P(V)-P(V) Coupling Reaction.

Biomolecules containing adenosine di- or triphosphate (ADP or ATP) are crucial for diverse biological processes. Synthesis of these biomolecules and development of their chemical probes are important to elucidate their functions. Enabling reproducible and high-yielding access to these ADP- and ATP-containing molecules via conventional P(III)-P(V) and P(V)-P(V) coupling reactions is challenging owing to water content in highly polar phosphate-containing substrates. Herein, we report an efficient and reliable method for protecting-group-free P(V)-P(V) coupling reaction through in situ activation of phosphates using hydrolysis-stable 2-[N-(2-methylimidazoyl)]-1,3-dimethylimidazolinium chloride (2-MeImIm-Cl), providing the corresponding electrophilic P(V) intermediates for subsequent nucleophilic attack using their coupling partners. This P(V)-P(V) coupling reaction proceeded even in a wet reaction medium and showed a broad substrate scope, accommodating protecting-group-free synthesis of ADP-ribose and nicotinamide adenine diphosphate analogs, ATP-containing biomolecules, and ADP-ribosyl peptides.

Long-term prognosis after endoscopic submucosal dissection for esophageal cancer in older adult patients.

BACKGROUND: The validity of endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) in older individuals with comorbidities remains unclear. Therefore, this study evaluated the safety and efficacy of ESD and additional treatment for ESCC in older adult patients. METHODS: The clinicopathological characteristics and clinical outcomes of 398 consecutive older adult patients (≥ 65 years) with 505 lesions who underwent ESD for ESCC at the Hiroshima University Hospital between September 2007 and December 2019 were retrospectively evaluated. Additionally, the prognoses of 381 patients who were followed up for > 3 years were assessed. RESULTS: The mean patient age and procedure time were 73.1 ± 5.8 years and 77.1 ± 43.5 min, respectively. The histological en bloc resection rate was 98% (496/505). Postoperative stenosis, perforation, pneumonia, and delayed bleeding were conservatively treated in 82 (16%), 19 (4%), 15 (3%), and 5 (1%) patients, respectively. The 5-year overall and disease-specific survival rates were 78.9% and 98.0%, respectively (mean follow-up time: 71.1 ± 37.3 months). Multivariate analysis showed that age and the American Society of Anesthesiologists classification of physical status class ≥III (hazard ratio: 1.27; 95% confidence interval: 1.01-1.59, p = 0.0392) were independently associated with overall survival. A significantly lower overall survival rate was observed in the high-risk follow-up group than in the low-risk follow-up and high-risk additional treatment groups (p < 0.01). However, no significant difference in disease-specific survival was observed among the three groups. CONCLUSIONS: ESD is safe for ESCC treatment in patients aged ≥ 65 years. However, additional treatments should be considered based on the patient's general condition.

Spontaneous differentiation of human induced pluripotent stem cells to odorant-responsive olfactory sensory neurons.

Pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells (iPSCs), can differentiate into almost all cell types and are anticipated to have significant applications in the field of regenerative medicine. However, there are no reports of successfully directing iPSCs to become functional olfactory sensory neurons (OSNs) capable of selectively receiving odorant compounds. In this study, we employed dual SMAD inhibition and fibroblast growth factor 8 (FGF-8, reported to dictate olfactory fates) along with N-2 and B-27 supplements in the culture medium to efficiently induce the differentiation of iPSCs into neuronal cells with olfactory function through olfactory placode. Temporal gene expression and expression of OSN-specific markers during differentiation indicated that the expression of olfactory marker proteins and various olfactory receptors (ORs), which are markers of mature OSNs, was observed after approximately one month of differentiation culture, irrespective of the differentiation cues, suggesting differentiation into OSNs. Cells that exhibited specific responses to odorant compounds were identified after administering odorant compounds to differentiated iPSC-derived OSNs. This suggests the spontaneous generation of functional OSNs expressing diverse ORs that respond to odorant compounds from iPSCs.

Analysis of anti-tumor effect and mechanism of GLS1 inhibitor CB-839 in colorectal cancer using a stroma-abundant tumor model.

BACKGROUND: Glutaminase 1 (GLS1), a key enzyme in glutamine metabolism in cancer cells, acts as a tumor promoter and could be a potential therapeutic target. CB-839, a GLS1-specific inhibitor, was developed recently. Herein, we aimed to elucidate the anti-tumor effects and mechanism of action of CB-839 in colorectal cancer (CRC). METHODS: Using the UCSC Xena public database, we evaluated GLS1 expression in various cancers. Immunostaining for GLS1 was performed on 154 surgically resected human CRC specimens. Subsequently, we examined the GLS1 mRNA expression levels in eight CRC cell lines and evaluated the association between GLS1 expression and CB-839 efficacy. To create a reproducible CRC model with abundant stroma and an allogeneic immune response, we co-transplanted CT26 and stem cells into BALB/c mice and treated them with CB-839. Finally, RNA sequencing of mouse tumors was performed. RESULTS: Database analysis showed higher GLS1 expression in CRC tissues than in normal colon tissues. Clinical samples from 114 of the 154 patients with CRC showed positive GLS1 expression. GLS1 expression in clinical CRC tissues correlated with vascular invasion. CB-839 treatment inhibited cancer cell proliferation depending on GLS1 expression in vitro and inhibited tumor growth and metastasis in the CRC mouse model. RNA sequencing revealed that CB-839 treatment inhibited stromal activation, tumor growth, migration, and angiogenesis. These findings were validated through in vitro and in vivo experiments and clinical specimen analysis. CONCLUSIONS: GLS1 expression in CRC plays important roles in tumor progression. CB-839 has inhibitory effects on cancer proliferation and the tumor microenvironment.

Assessing genetic diversity and geographical differentiation in a global collection of wild soybean (Glycine soja Sieb. et Zucc.) and assigning a mini-core collection.

Wild soybean (Glycine soja), the ancestor of the cultivated soybean (G. max), is a crucial resource for capturing the genetic diversity of soybean species. In this study, we used a set of 78 genome-wide microsatellite markers to analyse the genetic diversity and geographic differentiation patterns in a global collection of 2,050 G. soja accessions and a mini-core collection of G. max stored in two public seed banks. We observed a notable reduction in the genetic diversity of G. max compared with G. soja and identified a close phylogenetic relationship between G. max and a G. soja subpopulation located in central China. Furthermore, we revealed substantial genetic divergence between northern and southern subpopulations, accompanied by diminished genetic diversity in the northern subpopulations. Two clusters were discovered among the accessions from north-eastern China-one genetically close to those from South Korea and Southern Japan, and another close to those from Amur Oblast, Russia. Finally, 192 accessions were assigned to a mini-core collection of G. soja, retaining 73.8% of the alleles detected in the entire collection. This mini-core collection is accessible to those who need it, facilitating efficient evaluation and utilization of G. soja genetic resources in soybean breeding initiatives.

Verrucous gastritis-like lesion in intramucosal Helicobacter pylori-uninfected signet ring cell carcinoma with poorly differentiated adenocarcinoma.

In Japan, accessible Helicobacter pylori (Hp) eradication therapy is associated with an increase in the prevalence of gastric cancers (GCs) in Hp uninfected stomachs. Signet ring cell carcinoma (SRCC) is the most common of these GCs. Intramucosal SRCC with poorly differentiated adenocarcinoma (PDA) occurring in Hp uninfected gastric mucosa is rare; furthermore, many Hp uninfected pure SRCCs exhibit discoloration and flat or slightly depressed lesions, and morphological elevation is relatively rare. We report a case of intramucosal SRCC with PDA with an elevated, verrucous gastritis-like lesion in a 57-year-old male patient. In the present case, the PDA area showed dense tumor cell growth and coexisting desmoplastic and fibrotic reactions. Histopathology and immunohistochemical staining identified extensive fibromuscular obliteration with smooth muscle bundles extending from the muscularis mucosa into the lamina propria. The patient underwent curative endoscopic submucosal dissection. The reporting and analysis of such rare cases may lead to a better understanding of the characteristics of advanced Hp uninfected GCs.

Clinicopathological and genomic features of superficial esophageal squamous cell carcinomas in nondrinker, nonsmoker females.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is sometimes detected in non-drinker and non-smoker females who are considered to have very low risk of ESCC development in daily practice. This study examined the clinicopathological and genomic characteristics of ESCCs in females with no history of drinking and smoking. METHODS: The sample comprised 118 ESCC lesions occurring in 95 female patients who underwent endoscopic submucosal dissection at our department between January 2008 and December 2019. The patients were categorized into two groups: 51 lesions in 49 patients with no history of drinking and smoking (nondrinker/nonsmoker [NDNS] group) and 69 lesions in 45 patients with a history of drinking or smoking (drinker/smoker [DS] group). We analyzed the differences in clinicopathological and cancerous genomic characteristics between the groups. Significant genomic alterations were validated using immunohistochemistry. RESULTS: Multiple logistic regression revealed that older age, fewer multiple Lugol-voiding lesions (LVLs), and reflux esophagitis (RE) were independently associated with the occurrence of ESCCs in the NDNS group. ESCC lesions in the NDNS group were predominantly located in the mid-thoracic esophagus, posterior wall side, with 0-IIa, the aspect ratio of the lesion >2 (vertical/horizontal), and endoscopic keratinization. Genetic analysis showed that CDKN2A driver alterations were significantly more frequent and KMT2D alterations were significantly less frequent in the NDNS group than in the DS group. KMT2D alterations were strongly correlated with immunostaining. CONCLUSION: Older nondrinker, nonsmoker females with RE and fewer multiple LVLs may develop longitudinal 0-IIa ESCC with keratinization of the posterior wall of the mid-thoracic esophagus. ESCCs in nondrinker, nonsmoker females had fewer KMT2D alterations and more CDKN2A alterations, which may be a biomarker for treatment.

Association of Preoperative and Postoperative Plasma Syndecan-1 and Colorectal Cancer Outcome.

BACKGROUND/AIM: A three-dimensional network constructed using glycocalyx (GCX) extends throughout the cancer cell nest in human colorectal cancer (CRC). GCX was found to be closely related to cancer. We examined the prognostic correlation and potential of syndecan-1 (SDC1), a representative proteoglycan of GCX, as a biomarker. PATIENTS AND METHODS: We analyzed SDC1 in the transcriptomic profiles of a major publicly available CRC cohort from The Cancer Genome Atlas (TCGA) using a computational algorithm. We investigated serum SDC1 levels preoperatively and on postoperative day seven in 48 patients with stage I-III CRC who underwent surgery during July-December 2019 at Gifu University Hospital. RESULTS: For TCGA, no significant differences existed between the high and low SDC1 expression groups regarding disease-free, disease-specific, and overall survival for stage I-III, and only overall survival for stage IV was significantly different. In our study, among the 48 patients, 17 (no recurrence), 13 (1 recurrence), and 18 (10 recurrences) had stage I-III, respectively. Preoperative and postoperative day 7 SDC1 levels for patients with stage I-III were 10.7±2.3 and 9.9±3.1 ng/ml (p=0.40), 11.1±1.7 and 10.1±0.8 ng/ml (p=0.07), and 10.3±2.0 and 9.5±1.4 ng/ml (p=0.15), respectively. In stage II and III, patients were divided into two groups according to differences between preoperative and postoperative SDC1 levels (SDC1pre-pro). SDC1pre-pro ≤0 group significantly prolonged disease-free survival compared with SDC1pre-pro >0 group (p=0.048). CONCLUSION: Dynamic change in serum SDC1 levels serves as a prognostic biomarker for stage II and III colorectal cancer.

Pancreatic injury in patients treated with immune checkpoint inhibitors: a retrospective multicenterstudy.

BACKGROUND: Immune checkpoint inhibitor-related pancreatic injury (ICI-PI) is a rare occurrence, which has not been reported in detail. We conducted a retrospective multicenter study to determine the clinical characteristics, risk factors, and treatment of ICI-PI. METHODS: We reviewed the medical records of patients who received ICIs for malignant tumors between April 2014 and April 2019 at 16 participating hospitals. Patients with elevated pancreatic enzymes or pancreatitis were identified and classified using the Common terminology Criteria for Adverse Events (CTCAE) ver.5.0). The number of patients with pancreatic enzyme elevation was determined and those with pancreatic enzyme elevation of ≥ grade 3 according to CTCAE ver.5.0, or pancreatitis underwent detailed analysis for ICI-PI. RESULTS: The study enrolled 1069 patients. Nineteen patients (1.8%) had ICI-PI, 5 (0.5%) of whom also had pancreatitis. Four patients had mild pancreatitis, whereas 1 patient had severe pancreatitis, culminating in death. Steroid therapy was administered to 7 of 19 patients, which led to ICI-PI improvement in 5 patients. On the other hand, ICI-PI improved in 9 of 12 patients who were not administered steroid therapy. Six of the 14 patients with ICI-PI improvement were rechallenged with ICI, and ICI-PI relapse occurred in only 1 patient (16.7%), which improved with ICI discontinuation and steroid therapy. CONCLUSIONS: ICI-PI is a rare occurrence, with a low incidence of pancreatitis, which followed a very serious course in one patient. Although the benefit of steroid therapy for ICI-PI is unclear, ICI rechallenge is acceptable after improvement of ICI-PI without pancreatitis.