Background/Aims: Optimal risk stratification based on simplified geriatric assessment to predict treatment-related toxicity and survival needs to be clarified in older patients with diffuse large B-cell lymphoma (DLBCL). Methods: This multicenter prospective cohort study enrolled newly diagnosed patients with DLBCL (≥ 65 yr) between September 2015 and April 2018. A simplified geriatric assessment was performed at baseline using Activities of Daily Living (ADL), Instrumental ADL (IADL), and Charlson’s Comorbidity Index (CCI). The primary endpoint was event-free survival (EFS). Results: The study included 249 patients, the median age was 74 years (range, 65-88), and 125 (50.2%) were female. In multivariable Cox analysis, ADL, IADL, CCI, and age were independent factors for EFS; an integrated geriatric score was derived and the patients stratified into three geriatric categories: fit (n = 162, 65.1%), intermediate-fit (n = 25, 10.0%), and frail (n = 62, 24.9%). The established geriatric model was significantly associated with EFS (fit vs. intermediate-fit, HR 2.61, p < 0.001; fit vs. frail, HR 4.61, p < 0.001) and outperformed each covariate alone or in combination. In 87 intermediate-fit or frail patients, the relative doxorubicin dose intensity (RDDI) ≥ 62.4% was significantly associated with worse EFS (HR, 2.15, 95% CI 1.30–3.53, p = 0.002). It was related with a higher incidence of grade ≥ 3 symptomatic non-hematologic toxicities (63.2% vs. 27.8%, p < 0.001) and earlier treatment discontinuation (34.5% vs. 8.0%, p < 0.001) in patients with RDDI ≥ 62.4% than in those with RDDI < 62.4%. Conclusions This model integrating simplified geriatric assessment can risk-stratify older patients with DLBCL and identify those who are highly vulnerable to standard dose-intensity chemoimmunotherapy.

Background/Aims: The Gout Impact Scale (GIS), a part of the Gout Assessment Questionnaire 2.0, is used to measure gout-specific health-related quality of life (HRQOL). Although several studies have been conducted on the factors affecting the HRQOL of patients with gout, few have focused on lifestyle factors. This study aimed to investigate the correlation between lifestyle habits and HRQOL using the GIS in patients with gout. Methods: We used data from the Urate-Lowering TheRApy in Gout (ULTRA) registry, a prospective cohort of Korean patients with gout treated at multiple centers nationwide. The patients were aged ≥18 years and met the 2015 American College of Rheumatology/European League Against Rheumatism gout classification criteria. They were asked to complete a GIS and questions regarding their lifestyle habits at enrollment. Results: The study included 232 patients. ‘Gout concern overall’ scores in the GIS were significantly lower in patients who exercised more frequently and consumed soft drinks and meat less, and ‘well-being during attack’ scores were significantly lower in patients who consumed vegetables and exercised more frequently. The frequency of vegetable consumption had a negative linear relationship with the ‘well-being during attack’ and ‘gout concern during attack’ scores (p = 0.01, p = 0.001, respectively). The frequency of exercise had a negative linear relationship with the ‘gout concern overall’ and ‘gout concern during attack’ scores (p = 0.04 and p = 0.002, respectively). Conclusions Patients with gout who frequently consumed vegetables and exercised regularly experienced less impact of gout, exhibiting a better GIS that represented HRQOL.

Background/Aims: Achalasia is an esophageal motor disorder that leads to functional esophageal obstruction. Food stasis and bacterial fermentation can predispose an individual to esophageal mucosal inflammation, causing multifocal dysplasia and increasing the risk of developing esophageal squamous cell carcinoma. We aimed to evaluate esophageal mucosal alterations in achalasia patients and determine clinical factors associated with the histopathological findings. Methods: From 2009 to 2013, we obtained endoscopic biopsies from the lower and middle esophagus of 22 patients with achalasia and 17 controls. Patients’ clinical data and histological severity of esophagitis were retrospectively analyzed. Additionally, immunohistochemical staining for CD3, CD20, Ki-67, and p53 was conducted. Results: The median age of achalasia patients was 49.5 years (range, 27 to 82 years), and there were nine males (40.9%). The median symptom duration was 5.8 years (range, 1 to 33.5 years), and 10 patients (45%) underwent previous treatment (nine, balloon dilation; one, botulinum toxin injection). Achalasia patients had significantly more severe esophagitis than did controls (p=0.001, lower esophagus; p=0.008, middle esophagus), and the number of CD3-positive lymphocytes exceeded that of CD20-positive lymphocytes (p<0.001). Achalasia patients also had a higher esophageal Ki-67 proliferation index (p=0.048). Although statistically nonsignificant, p53 expression was only observed in achalasia patients. There was no association between the histological severity of esophagitis and other clinicopathological findings. Conclusions Achalasia patients showed significantly severe histological esophagitis and a high Ki-67 proliferation index, indicating an increased risk of neoplastic progression. Therefore, careful endoscopic inspection is necessary for the early detection of superficial neoplasia in these patients.

Purpose: Microbiota manipulation through selected probiotics may be a promising tool to prevent cancer development as well as onset, to improve clinical efficacy for cancer treatments. The purpose of this study was to evaluate change in microbiota composition after-probiotics supplementation and assessed the efficacy of probiotics in improving quality of life (QOL) in postoperative cancer patients. Methods: Stool samples were collected from 30 cancer patients from February to October 2020 before (group I) and after (group II) 8 weeks of probiotics supplementation. We performed 16S ribosomal RNA gene sequencing to evaluate differences in gut microbiota between groups by comparing gut microbiota diversity, overall composition, and taxonomic signature abundance. The health-related QOL was evaluated through the EORTC Quality of life Questionnaire Core 30 questionnaire. Results: Statistically significant differences were noted in group II; increase of Shannon and Simpson index (P = 0.004 and P = 0.001), decrease of Bacteroidetes and Fusobacteria at the phylum level (P = 0.032 and P = 0.014, retrospectively), increased of beneficial bacteria such as Weissella (0.096% vs. 0.361%, P < 0.004), Lactococcus (0.023% vs. 0.16%, P < 0.001), and Catenibacterium (0.0% vs. 0.005%, P < 0.042) at the genus level. There was a significant improvement in sleep disturbance (P = 0.039) in group II. Conclusion Gut microbiota in cancer patients can be manipulated by specific probiotic strains, result in an altered microbiota. Microbiota modulation by probiotics can be considered as part of a supplement that helps to increase gut microbiota diversity and improve QOL in cancer patients after surgery.

Purpose: While the incidence of Barrett’s neoplasia has been increasing in Western countries, the disease remains rare in Asian countries. Therefore, very few studies have investigated the endoscopic treatment for Barrett’s neoplasia in Korea. Endoscopic submucosal dissection (ESD) enables en bloc and complete resection of gastrointestinal neoplastic lesions. This study aimed to evaluate the therapeutic outcomes of ESD for Barrett’s neoplasia in a single center in Korea and to examine the predictive factors for incomplete resection. Materials and Methods: We conducted a retrospective observational study of 18 patients who underwent ESD for superficial Barrett’s neoplasia (dysplasia and early cancer) between January 2010 and December 2019 at Pusan National University Hospital. The therapeutic outcomes of ESD and procedure-related complications were analyzed. Results: En bloc resection, complete resection, and curative resection were performed in 94%, 72%, and 61% of patients, respectively. Histopathology (submucosal or deeper invasion of the tumor) was a significant predictive factor for incomplete resection (P=0.047). Procedure-related bleeding and stenosis were not observed, whereas perforation occurred in one case. During the median follow-up period of 12 months (range, 6–74 months), local recurrence occurred in 2 patients with incomplete resection, one patient underwent repeat ESD, and the other patient received concurrent chemoradiotherapy. The 3-year overall and disease-specific survival rates were 73% and 93%, respectively. Conclusions ESD seems to be an effective and safe treatment for superficial Barrett’s neoplasia in Korea. Nevertheless, the suitability of ESD for Barrett’s cancer cases should be determined considering the high risk of deep submucosal invasion.

Background/Aims: Achalasia is an esophageal motor disorder that leads to functional esophageal obstruction. Food stasis and bacterial fermentation can predispose an individual to esophageal mucosal inflammation, causing multifocal dysplasia and increasing the risk of developing esophageal squamous cell carcinoma. We aimed to evaluate esophageal mucosal alterations in achalasia patients and determine clinical factors associated with the histopathological findings. Methods: From 2009 to 2013, we obtained endoscopic biopsies from the lower and middle esophagus of 22 patients with achalasia and 17 controls. Patients’ clinical data and histological severity of esophagitis were retrospectively analyzed. Additionally, immunohistochemical staining for CD3, CD20, Ki-67, and p53 was conducted. Results: The median age of achalasia patients was 49.5 years (range, 27 to 82 years), and there were nine males (40.9%). The median symptom duration was 5.8 years (range, 1 to 33.5 years), and 10 patients (45%) underwent previous treatment (nine, balloon dilation; one, botulinum toxin injection). Achalasia patients had significantly more severe esophagitis than did controls (p=0.001, lower esophagus; p=0.008, middle esophagus), and the number of CD3-positive lymphocytes exceeded that of CD20-positive lymphocytes (p<0.001). Achalasia patients also had a higher esophageal Ki-67 proliferation index (p=0.048). Although statistically nonsignificant, p53 expression was only observed in achalasia patients. There was no association between the histological severity of esophagitis and other clinicopathological findings. Conclusions Achalasia patients showed significantly severe histological esophagitis and a high Ki-67 proliferation index, indicating an increased risk of neoplastic progression. Therefore, careful endoscopic inspection is necessary for the early detection of superficial neoplasia in these patients.

METHODS: The efficiency of electroporation-based delivery of AsCpf1/mRNA and AsCpf1/RNP to target exon 3 of leukemia inhibitory factor (Lif) into mouse zygotes was evaluated. Embryos that developed to the two-cell stage after zygote electroporation were transferred into the oviducts of surrogate mothers to produce AsCpf1-mediated LIF KO mice. The genome editing efficiency of blastocysts and pups was tested using the T7E1 assay and/or DNA sequencing. Congenital abnormalities and reproductive phenotypes in LIF KO mice produced by electroporation with AsCpf1/RNP were examined. RESULTS: Survival and two-cell development of electroporated zygotes were comparable between the AsCpf1/mRNA and AsCpf1/RNP groups, whereas genome editing efficiency was relatively higher in the AsCpf1/RNP group (13.3% vs 18.1% at blastocyst and 33.3% vs 45.5% at offspring), respectively. Two mouse lines with a frameshift mutation in exon 3 of the Lif gene were established from the AsCpf1/RNP group. All congenital abnormalities of LIF KO mice produced by AsCpf1/RNP electroporation were observed. AsCpf1-mediated LIF KO mice showed postnatal growth retardation and implantation failure, both of which are major phenotypes of LIF KO mice generated by conventional gene targeting. CONCLUSION Electroporation of AsCpf1/RNP at the zygote stage is an efficient genome editing method to produce KO mice.

METHODS: The efficiency of electroporation-based delivery of AsCpf1/mRNA and AsCpf1/RNP to target exon 3 of leukemia inhibitory factor (Lif) into mouse zygotes was evaluated. Embryos that developed to the two-cell stage after zygote electroporation were transferred into the oviducts of surrogate mothers to produce AsCpf1-mediated LIF KO mice. The genome editing efficiency of blastocysts and pups was tested using the T7E1 assay and/or DNA sequencing. Congenital abnormalities and reproductive phenotypes in LIF KO mice produced by electroporation with AsCpf1/RNP were examined. RESULTS: Survival and two-cell development of electroporated zygotes were comparable between the AsCpf1/mRNA and AsCpf1/RNP groups, whereas genome editing efficiency was relatively higher in the AsCpf1/RNP group (13.3% vs 18.1% at blastocyst and 33.3% vs 45.5% at offspring), respectively. Two mouse lines with a frameshift mutation in exon 3 of the Lif gene were established from the AsCpf1/RNP group. All congenital abnormalities of LIF KO mice produced by AsCpf1/RNP electroporation were observed. AsCpf1-mediated LIF KO mice showed postnatal growth retardation and implantation failure, both of which are major phenotypes of LIF KO mice generated by conventional gene targeting. CONCLUSION Electroporation of AsCpf1/RNP at the zygote stage is an efficient genome editing method to produce KO mice.

We report a case of bleeding ileal varices associated with intra-abdominal adhesions after colectomy which was successfully diagnosed using capsule endoscopy. A 77-year-old woman visited the emergency department for several episodes of melena. She had a medical history of neoadjuvant chemo-radiation therapy and subsequent surgery for rectal cancer 6 years previously. Conventional diagnostic examinations including upper endoscopy, colonoscopy, and abdominal computed tomography could not detect any bleeding focus, however, following capsule endoscopy revealed venous dilatations with some fresh blood in the distal ileum, indicating bleeding ileal varices. The patient underwent exploratory laparotomy and the affected ileum was successfully resected. No further gastrointestinal bleeding occurred during the 6 months follow-up. Small intestinal varices are important differential for obscure gastrointestinal bleeding especially in patients with a history of abdominal surgery in the absence of liver cirrhosis, and capsule endoscopy can be a good option for diagnosing small intestinal varices.
Aged ; Capsule Endoscopy* ; Colectomy* ; Colonoscopy ; Dilatation ; Emergency Service, Hospital ; Endoscopy ; Female ; Follow-Up Studies ; Gastrointestinal Hemorrhage ; Hemorrhage* ; Humans ; Ileum ; Laparotomy ; Liver Cirrhosis ; Melena ; Rectal Neoplasms ; Varicose Veins*

PURPOSE: Little is known about the clinical value of peripheral blood immune profiling. Here, we aimed to identify colorectal cancer (CRC)-related peripheral blood immune cells and develop liquid biopsy-based immune profiling models for CRC diagnosis. METHODS: Peripheral blood from 131 preoperative patients with CRC and 174 healthy controls was analyzed by flow cytometry and automated hematology. CRC-related immune factors were identified by comparing the mean values of immune cell percentages and counts. Subsequently, CRC diagnostic algorithms were constructed using binary logistic regression. RESULTS: Significant differences were observed in percentages and counts of white blood cells, lymphocytes, neutrophils, regulatory T cells, and myeloid-derived suppressor cells (MDSCs) of patients and controls. The neutrophil/lymphocyte and Th1/Th2 ratios were also significantly different. Likewise, the percentages and counts of peripheral blood programed death 1, cytotoxic T lymphocyte antigen 4, B-and T-lymphocyte attenuator, and lymphocyte activation gene-3 were higher in patients with CRC. The binary logistic regression model included 12 variables, age, CD3+%, NK%, CD4+CD279+%, CD4+CD25+%, CD4+CD152+%, CD3+CD366+%, CD3+CD272+%, CD3+CD223+%, CD158b−CD314+CD3−CD56+%, Th2%, and MDSCs cells/µL, for the prediction of cancer. Results of retrospective and prospective evaluation of the area under the curve, sensitivity, and specificity were 0.980 and 0.940, 91.53% and 85.80%, and 93.50% and 86.20%, respectively. CONCLUSION: Peripheral blood immune profiling may be valuable in evaluating the immunity of CRC patients. Our liquid biopsy-based immune diagnostic method and its algorithms may serve as a novel tool for CRC diagnosis. Future largescale studies are needed for better characterization of its diagnostic value and potential for clinical application.
Blood Cells ; Colorectal Neoplasms* ; CTLA-4 Antigen ; Diagnosis ; Early Detection of Cancer ; Flow Cytometry ; Hematology ; Humans ; Immunologic Factors ; Leukocytes ; Logistic Models ; Lymphocyte Activation ; Lymphocytes ; Methods ; Neutrophils ; Prospective Studies ; Retrospective Studies ; Sensitivity and Specificity ; T-Lymphocytes ; T-Lymphocytes, Regulatory