Real-world survival after colorectal surgery for malignancy in Korean patients with chronic kidney disease: an analysis of Korean healthcare big data, 2002–2019

Purpose@#Globally, chronic kidney disease (CKD) is common and has been associated with an increased risk of colorectal cancer (CRC). There is a dearth of literature on the real-world morbidity and mortality associated with CKD comorbid with CRC. This study was performed to evaluate real-world survival outcomes of colorectal malignancy in Korean CKD patients. @*Methods@#The National Health Insurance Service of Korea provided data on patients who underwent surgical resection among patients diagnosed with CRC from 2002 to 2019. @*Results@#A total of 219,550 patients were included: 6,181 patients with underlying CKD and 213,369 patients without it.Each morbidity was significantly higher in the CKD-CRC group, and the postoperative mortality rates for the 30-day (3.11% vs. 1.78%, P < 0.001), 60-day (5.95% vs. 3.83%, P < 0.001), and 90-day mortality rate (8.12% vs. 5.32%, P < 0.001) were significantly higher in the CKD group. The median survival time (MST, year) was significantly lower in the CKD-CRC group (5.63; interquartile range [IQR], 5.26–5.91) than in the non-CKD-CRC group (8.71; IQR, 8.37–8.93). MST was significantly lower among CKD patients who received chemotherapy after adjustment by multivariate analysis (adjusted hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.37–1.49; P < 0.001]). Subgroup analysis showed that in the CKD-CRC group, MST was lower in patients who received dialysis than in those who did not, even after multivariate analysis (adjusted HR, 2.38;95% CI, 2.20–2.58; P < 0.001). @*Conclusion@#Prevention of CKD-to-end-stage renal disease progression should be adopted as a strategy to increase postoperative survival, along with active surveillance and cancer treatment.

Induction of Peptide-specific CTL Activity and Inhibition of Tumor Growth Following Immunization with Nanoparticles Coated with Tumor Peptide-MHC-I Complexes

Tumor peptides associated with MHC class I molecules or their synthetic variants have attracted great attention for their potential use as vaccines to induce tumor-specific CTLs. However, the outcome of clinical trials of peptide-based tumor vaccines has been disappointing. There are various reasons for this lack of success, such as difficulties in delivering the peptides specifically to professional Ag-presenting cells, short peptide halflife in vivo, and limited peptide immunogenicity. We report here a novel peptide vaccination strategy that efficiently induces peptide-specific CTLs. Nanoparticles (NPs) were fabricated from a biodegradable polymer, poly(D,L-lactic-co-glycolic acid), attached to H-2Kb molecules, and then the natural peptide epitopes associated with the H-2K b molecules were exchanged with a model tumor peptide, SIINFEKL (OVA 257-268 ). These NPs were efficiently phagocytosed by immature dendritic cells (DCs), inducing DC maturation and activation. In addition, the DCs that phagocytosed SIINFEKL-pulsed NPs potently activated SIINFEKL-H-2K b complex-specific CD8 + T cells via cross-presentation of SIINFEKL. In vivo studies showed that intravenous administration of SIINFEKL-pulsed NPs effectively generated SIINFEKLspecific CD8 + T cells in both normal and tumor-bearing mice. Furthermore, intravenous administration of SIINFEKL-pulsed NPs into EG7.OVA tumor-bearing mice almost completely inhibited the tumor growth. These results demonstrate that vaccination with polymeric NPs coated with tumor peptide-MHC-I complexes is a novel strategy for efficient induction of tumor-specific CTLs.

COVID-19 Antiviral and Treatment Candidates: Current Status

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 has severely impacted global health and economy. There is currently no effective approved treatment for COVID-19; although vaccines have been granted emergency use authorization in several countries, they are currently only administered to high-risk individuals, thereby leaving a gap in virus control measures. The scientific and clinical communities and drug manufacturers have collaborated to speed up the discovery of potential therapies for COVID-19 by taking advantage of currently approved drugs as well as investigatory agents in clinical trials. In this review, we stratified some of these candidates based on their potential targets in the progression of COVID-19 and discuss some of the results of ongoing clinical evaluations

Adjuvanticity of Processed Aloe vera gel for Influenza Vaccination in Mice

The effectiveness of current influenza vaccines is considered suboptimal, and 1 way to improve the vaccines is using adjuvants. However, the current pool of adjuvants used in influenza vaccination is limited due to safety concerns. Aloe vera, or aloe, has been shown to have immunomodulatory functions and to be safe for oral intake. In this study, we explored the potential of orally administered processed Aloe vera gel (PAG) as an adjuvant for influenza vaccines in C57BL/6 mice. We first evaluated its adjuvanticity with a split-type pandemic H1N1 (pH1N1) Ag by subjecting the mice to lethal homologous influenza challenge. Oral PAG administration with the pH1N1 Ag increased survival rates in mice to levels similar to those of alum and MF59, which are currently used as adjuvants in influenza vaccine formulations.Similarly, oral PAG administration improved the survival of mice immunized with a commercial trivalent influenza vaccine against lethal homologous and heterologous virus challenge. PAG also increased hemagglutination inhibition and virus neutralization Ab titers against homologous and heterologous influenza strains following immunization with the split-type pH1N1 Ag or the commercial trivalent vaccine. Therefore, this study demonstrates that PAG may potentially be used as an adjuvant for influenza vaccines.

Evaluation of Protective Immunity of Peptide Vaccines Composed of a 15-mer N-terminal Matrix Protein 2 and a Helper T-Cell Epitope Derived from Influenza A Virus

The matrix protein 2 of influenza A virus (IFAV) has a relatively conserved ectodomain (M2e) composed of 23 amino acids, and M2e-based vaccines have been suggested to induce broad protective immunity in mice. In this study, we investigated whether N-terminal sequence of M2e (nM2e)-based vaccines with more conserved nM2e could induce influenza viral neutralizing activity. We constructed linear peptide vaccines with an nM2e sequence for PR8 virus (nM2Pr) connected to a probable 17-mer IFAV-derived helper T-cell epitope (ThE: T1, T2, or T3) at its N- or C-terminus. The peptide vaccines induced significant production of nM2e Abs regardless of either type or location of the ThE-epitope in BALB/c mice, while only T3 was effective in C57BL/6 mice. The Abs against nM2Pr-T3 elicited broader binding affinities to the nM2e peptides derived from various IFAVs than those against T3-nM2Pr. In addition, the nM2e-based vaccines efficiently protected the immunized mice from the lethal challenge of PR8 virus. These results suggest that the more conserved nM2e without cysteine will be useful for development of universal peptide vaccines than M2e.

Poly(rC) binding protein 2 acts as a negative regulator of IRES-mediated translation of Hr mRNA

During the hair follicle (HF) cycle, HR protein expression is not concordant with the presence of the Hr mRNA transcript, suggesting an elaborate regulation of Hr gene expression. Here we present evidence that the 5′ untranslated region (UTR) of the Hr gene has internal ribosome entry site (IRES) activity and this activity is regulated by the binding of poly (rC) binding protein 2 (PCBP2) to Hr mRNA. Overexpression and knockdown of PCBP2 resulted in a decrease in Hr 5′ UTR IRES activity and an increase in HR protein expression without changing mRNA levels. We also found that this regulation was disrupted in a mutant Hr 5′ UTR that has a mutation responsible for Marie Unna hereditary hypotrichosis (MUHH) in both mice and humans. These findings suggest that Hr mRNA expression is regulated at the post-transcriptional level via IRES-mediated translation control through interaction with PCPB2, but not in MUHH.

Surgical treatment for high-grade pseudomyxoma peritonei originated from appendix: Analysis of clinical outcomes of repeated debulking surgery

PURPOSE: To evaluate the effect of repeated debulking surgery for high-grade pseudomyxoma peritonei (PMP) originating from the appendix.METHODS: Between January 1998 and December 2014, fifty patients, who underwent debulking surgery for high-grade PMP originating from the appendix, were obtained from a prospectively collected database and retrospectively analyzed. Two groups according to the number of operations were divided and analyzed.RESULTS: A total of 118 operations were performed. Thirty-one patients received more than two operations. The median interval between operations was 18.2 months (range, 2–170 months). Complications developed after 26 operations (22.0%), including ileus (n=10), intra-abdominal fluid collection (n=7), surgical site infection (n=5), and others. There were two mortalities within 30 days after operation. Between two groups of patients who received one operation only and patients who received more than two operations, transfusion, diversion operation, and postoperative complication rate showed statistically significant differences. Two groups of patients had no differences in overall survival rates.CONCLUSION: Our results indicate that the number of operations does not affect the survival rate of high-grade appendiceal PMP, in which repeated debulking surgery is vital to relieve symptoms of the tumor burden.

Long-term Oncologic Outcomes of Obesity after Laparoscopic Surgery for Colorectal Cancer in Asian Patients

PURPOSE: The adverse effects of obesity on short-term surgical outcomes after laparoscopic colorectal surgery have been reported. However, the influence of obesity on long-term oncological outcomes after laparoscopic surgery in Asian patients has not been well understood. The aim of this study was to evaluate the effect of obesity on long-term oncologic outcomes in patients who underwent laparoscopic surgery for colorectal cancer. METHODS: Overall, 424 consecutive patients who underwent laparoscopic resection for colorectal cancer between January 2005 and July 2012 were included in this retrospective study. Patients were classified as non-obese (body mass index [BMI] <25.0 kg/m²) and obese (BMI ≥25.0 kg/m²) according to the categories proposed by the International Obesity Task Force. A survival analysis was performed using clinicopathologic characteristics, including obesity. RESULTS: Of the 424 patients, 325 (76.7%) were classified as non-obese and 99 (23.3%) as obese. The clinicopathologic characteristics of the obese and non-obese groups were similar, except that there were more underlying comorbidities, a lower frequency of smoking, and fewer tumors in rectum in the obese group. Results of the multivariate analysis showed that older age, elevated serum carcinoembryonic antigen, high-grade histology, advanced tumor stage, and perineural invasion were associated with poorer disease-free survival and overall survival. Obesity was not significantly associated with disease-free survival (hazard ratio [HR], 1.196; 95% confidence interval [CI], 0.686~2.086; p=0.528) or overall survival (HR, 1.156; 95% CI, 0.584~2.289; p=0.677). CONCLUSION: Laparoscopic surgery for colorectal cancer seems to be safe and feasible for obese patients in terms of long-term oncologic outcomes.

Erratum: Biofeedback Therapy Before Ileostomy Closure in Patients Undergoing Sphincter-Saving Surgery for Rectal Cancer: A Pilot Study

In this article, the sixth author's affiliation was misprinted unintentionally.

Biofeedback Therapy Before Ileostomy Closure in Patients Undergoing Sphincter-Saving Surgery for Rectal Cancer: A Pilot Study

PURPOSE: This study prospectively investigated the effects of biofeedback therapy on objective anorectal function and subjective bowel function in patients after sphincter-saving surgery for rectal cancer. METHODS: Sixteen patients who underwent an ileostomy were randomized into two groups, one receiving conservative management with the Kegel maneuver and the other receiving active biofeedback before ileostomy closure. Among them, 12 patients (mean age, 57.5 years; range, 38 to 69 years; 6 patients in each group) completed the study. Conservative management included lifestyle modifications, Kegel exercises, and medication. Patients were evaluated at baseline and at 1, 3, 6, and 12 months after ileostomy closure by using anal manometry, modified Wexner Incontinence Scores (WISs), and fecal incontinence quality of life (FI-QoL) scores. RESULTS: Before the ileostomy closure, the groups did not differ in baseline clinical characteristics or resting manometric parameters. After 12 months of follow-up, the biofeedback group demonstrated a statistically significant improvement in the mean maximum squeezing pressure (from 146.3 to 178.9, P = 0.002). However, no beneficial effect on the WIS was noted for biofeedback compared to conservative management alone. Overall, the FI-QoL scores were increased significantly in both groups after ileostomy closure (P = 0.006), but did not differ significantly between the two groups. CONCLUSION: Although the biofeedback therapy group demonstrated a statistically significant improvement in the maximum squeezing pressure, significant improvements in the WISs and the FI-QoL scores over time were noted in both groups. The study was terminated early because no therapeutic benefit of biofeedback had been demonstrated.

Relationship between food and nutrient intake and the risk of hypertriglyceridemia in Vietnamese women residing in Bavi: the Korean Genome and Epidemiology Study (KoGES)

The purpose of this study is to investigate the proportion and associated risk factors of hypertriglyceridemia in rural Vietnamese women. Research data were collected as part of the Korean Genome and Epidemiology Study (KoGES). A cross-sectional study of 957 Vietnamese women in their 20 to 30s was conducted in rural areas of Bavi, Vietnam. Subjects were classified as hypertriglyceridemic (serum TG > or = 150 mg/dL). Demographic, socio-economic details, anthropometric measurements, and blood profiles were recorded. The proportion of hypertriglyceridemic subjects was 22.0%, and the mean age of hypertriglyceridemics subjects was older than that of normo-triglyceridemic subjects (p < 0.05). In hypertriglyceridemic subjects, height, HDL-cholesterol, and LDL-cholesterol were significantly lower, compared to subjects with normo-triglyceridemia, while weight, body mass index, waist hip ratio, body fat %, blood pressure, fasting blood sugar, total cholesterol, and atherogenic index were higher, compared to those with normo-triglyceridemia. Intake of cereal and cereal products, total plant food, and cereal/potato fiber in subjects with hypertriglyceridemia was significantly higher, compared to normo-triglyceridemic subjects. Hypertriglyceridemic subjects had a significantly lower intake of animal calcium and retinol than normo-triglyceridemic subjects. Significant positive relationships were observed between the prevalence of hypertriglyceridemia and consumption of total plant food [OR (95% CI) for the highest tertile, compared to the lowest: 1.764 (1.131-2.750); p for trend = 0.008] and crude fiber [OR (95% CI) for the highest tertile compared to the lowest: 1.651 (1.092-2.497); p for trend = 0.027]. In addition, a significant inverse relationship was observed between the prevalence of hypertriglyceridemia and cholesterol intake [OR (95% CI) for the highest tertile, compared to the lowest: 0.601 (0.400-0.901); p for trend = 0.012]. These findings may provide basic data for use by policymakers and dieticians in future development of nutrition and health programs to encourage healthier eating habits, and to prevent hypertriglyceridemia advancing cardiovascular disease in rural Vietnamese women.

Prolonged shedding of the canine influenza H3N2 virus in nasal swabs of experimentally immunocompromised dogs

PURPOSE: The avian origin canine influenza virus H3N2 has been recently isolated and found to be currently in dog population in South Korea and China. The purpose of this study was to clarify the relationship between immunosuppressive glucocorticoids used in veterinary clinical practice and viral shedding pattern of influenza in dogs. MATERIALS AND METHODS: Eight conventional beagle dogs were divided into control infection group and immunocompromised group. Dogs of both groups were infected with H3N2 canine influenza virus (2x106.0 EID50/0.1 mL). Dogs in immunocompromised group were given orally 3.0 mg/kg prednisolone for 7 days. Virus shedding was monitored using real-time polymerase chain reaction. After necropsy, histopathologic lesions were compared. RESULTS: We found that immunocompromised dogs exhibited more prolonged (8 days vs. 13 days) and higher magnitude viral shedding than control group (peak titer of viral shedding 4.6 vs. 5.5 EID50). CONCLUSION: Restricted use of immunosuppressive drugs in the clinical setting might help control the rapid spread of H3N2 through local dog populations.

The Hairless Gene: A Putative Navigator of Hair Follicle Development

The Hairless (HR) gene regulates the expression of several target genes as a transcriptional corepressor of nuclear receptors. The hair follicle (HF), a small independent organ of the skin, resides in the epidermis and undergoes regenerative cycling for normal hair formation. HF development requires many genes and signaling pathways to function properly in time and space, one of them being the HR gene. Various mutations of the HR gene have been reported to cause the hair loss phenotype in rodents and humans. In recent studies, it has been suggested that the HR gene is a critical player in the regulation of the hair cycle and, thus, HF development. Furthermore, the HR gene is associated with the Wnt signaling pathway, which regulates roliferation and differentiation of cells and plays an essential role in hair and skin development. In this review, we summarize the mutations responsible for human hair disorders and discuss the roles of the HR gene in HF development.

Management of Appendicitis Presenting with Abscess or Mass

PURPOSE: Management strategy in acute appendicitis patients initially presenting with abscess or mass is surrounded with controversy. This study was performed to identify the outcomes of management for this condition. METHODS: We retrospectively analyzed prospectively registered 76 patients (male:female = 39:37; mean age, 50.8 years) with appendicitis presenting with abscess or mass over a 9-year period at the Seoul National University Hospital. Patients were divided into three groups (emergency operation group, delayed operation group, and follow-up group), and clinical characteristics and outcomes of treatment were investigated. RESULTS: Twenty-eight patients (36.8%) underwent an emergency operation. Of the remaining 48 patients, 20 (41.7%) were initially treated with conservative management through the use of antibiotics only; the other 28 (58.3%) with and additional ultrasound-guided percutaneous drainage of the abscess. Twenty-six (54.2%) patients underwent planned operations after conservative management, and 22 (45.8%) were followed without surgery (median duration, 37.8 month), of which 3 (13%) underwent an appendectomy due to recurrent appendicitis (mean of 56.7 days after initial attack). There were no statistical differences in types of operation performed (appendectomy or ileocecectomy), postoperative complications, and postoperative hospital stay among the patients who underwent emergency operations, delayed operations and operations for recurrence during follow-up. CONCLUSION: Although the recurrence rate was relatively low after conservative management for appendicitis patients presenting with abscess or mass, there was no difference in surgical outcome between the emergent, elective, or recurrent groups. Our results indicate that proper management of appendicitis with abscess or mass can be selected according to surgeon's preference.

Tissue-specific expression and subcellular localization of ALADIN, the absence of which causes human triple A syndrome

Triple A syndrome is a rare genetic disorder caused by mutations in the achalasia-addisonianism-alacrima syndrome (AAAS) gene which encodes a tryptophan aspartic acid (WD) repeat-containing protein named alacrima-achalasia-adrenal insufficiency neurologic disorder (ALADIN). Northern blot analysis shows that the 2.1 kb AAAS mRNA is expressed in various tissues with stronger expression in testis and pancreas. We show that human ALADIN is a protein with an apparent molecular weight of 60 kDa, and expressed in the adrenal gland, pituitary gland and pancreas. Furthermore, biochemical analysis using anti-ALADIN antibody supports the previous finding of the localization of ALADIN in the nuclear membrane. The mutations S544G and S544X show that alteration of S544 residue affects correct targeting of ALADIN to the nuclear membrane.

Clinical Outcomes after Discontinuation of Lamivudine in Chronic Hepatitis B Patients with Lamivudine Resistant HBV Mutant / 대한간학회지

BACKGROUND/AIMS: The therapeutic strategies of applying adefovir for treating lamivudine resistant HBV mutants are controversial. Thus, we observed the clinical outcomes after discontinuation of lamivudine to establish the timing to initiate adefovir therapy. METHODS: Fifty chronic hepatitis B (CHB) patients with lamivudine resistant HBV mutants who had received lamivudine for more than 12 months were included in the study. We investigated the clinical outcomes at 6 months after the end of treatment (EOT). We compared the serial clinical outcomes among respective groups based on serum ALT at the EOT and the clinical characteristics of patients with or without acute exacerbation (AE) and the HBeAg loss. We also investigated the predictive parameters of AE and HBeAg loss. RESULTS: Fifteen patients (30%) had experienced AE at 6 months after the EOT. Four patients received antiviral agents because of their hepatic decompensation. Patients with AE had higher serum ALT values and lower HBV DNA titers at EOT compared with those patients without AE. Serum ALT at the EOT was the predictive parameter of AE. Eight patients (21.6%) had newly developed HBeAg loss at 6 months after EOT. The total bilirubin at EOT was the predictive parameter of HBeAg loss. CONCLUSIONS: CHB patients with lamivudine resistant HBV mutants had favorable clinical outcomes at 6 months after EOT. Therefore, we can consider observing the clinical courses after discontinuation of lamivudine and it is not always required to overlap the adefovir for treating lamivudine resistant HBV mutants except for the treatment of patients with a high risk of developing decompensation.

A Case of Type I Duodenal Perforation Treated with Covered Metal Stent / 대한소화기내시경학회지

Endoscopic retrograde cholangiopancreatography (ERCP) has played an important role in diagnosis and management of biliary disease. Traditionally, duodenal perforations, rare complication of ERCP, have been managed surgically. However, in the past decade, there were arguments for surgical and nonsurgical management of ERCP-related duodenal perforations and reports of successful conservative treatment were increasing especially in patients with old age and poor medical conditions. We experienced a case of type I duodenal perforation following ERCP treated with covered metal stent in 74 years old female with duodenal invasion by Klatskin tumor.

Duodenal Perforation due to Hemoclipping for the Dieulafoy's Lesion in a Duodenal Diverticulum / 대한소화기내시경학회지

Duodenal diverticulum usually originates in the second portion of the duodenum and occasionally causes duodenal obstruction, hemorrhage, perforation and diverticulitis. A bleeding from Dieulafoy's lesion in a duodenal diverticulum is rare. It is not easily dignosed and treated by forward viewing endoscopy. Recently, a case was reported describing the hemorrhage from the Dieulafoy's lesion in a duodenal diverticulum which was treated by hemoclip with forward viewing endoscopy. Hemoclip application is considered to be the most appropriate endoscopic treatment, because sclerotherapy, electrocoagulation or band ligation for Dieulafoy's lesion in the duodenal diverticulum may increase risk of duodenal perforation. We report a case of duodenal perforation due to hemoclip application for the treatment of Dieulafoy's lesion in a duodenal diverticulum.

Two Cases of Hemobilia Associated with Common Bile Duct Stones / 대한소화기내시경학회지

Hemobilia is a disease caused by injury or conditions that cause the abnormal communication between intrahepatic blood vessels and biliary tract, resulting in leakage of blood into the biliary tract. In the past, trauma had been the most common cause of hemobilia. However, with the increasing invasive procedures in the hepatobiliary tract, iatrogenic origin has become the major cause of hemobilia. Also, non-traumatic etiologies of hemobilia include vascular malformation such as aneurysm, gallstone, inflammation, biliary tumor, hepatocellular carcinoma and coagulopathy. Among these non-traumatic etiologies, choledocholithiasis is a rare cause of hemobilia. The authors have experienced two cases of hemobilia caused by choledocholithiasis, which was diagnosed by abdominal ultrasonography, abdominal CT and duodenoscopy. Both patients were treated by the endoscopic sphincterotomy and stone removal with basket.

Postnatal Development of Brain -Derived Neurotrophic Factor: Immunoreactive Neuron System of the Rat Brain / 대한해부학회지

BDNF is a protein that allows the survival and differentiation of the central nervous system. In the present study, we have examined the postnatal development of BDNF -immunoreactive (IR) neuron system in the forebrain and the upper brain stem of the rat using immunohistochemistry. In the piriform cortex, claustrum, CA2 and 3, anterodorsal and paraventricular thalamic nucleus (nu.), ventromedial hypothalamic nu. and substantia nigra, BDNF-IR neurons were detected at postnatal day 1. BDNF-IR neurons in the anterior olfactory n., layers V and VI of the neocortex, claustrum, dentate gyrus, basolateral amygdaloid nu., paraventricular hypothalamic nu., mammillary nu. first appeared at postnatal 1 week of age and tended to increase in number as the rats grew. BDNF -IR neurons in ventromedial and paraventricular hypothalamic nu., mammillary nu., and substantia nigra decreased in number and none or only a few BDNF-IR neurons were seen in these areas of the adult rats. However, after treatment of colchicine, these areas showed numerous BDNF-IR neurons. BDNF-IR axon terminals were found in the septal nu., central amygdaloid nu., bed nu., of the stria terminalis, anterior ventral, anterior medial, interanteromedial and paravertricular thalamic nu., at postnatal day 1 and in dentate gyrus and paraventricular hypothalamic nu., at 1 week of age, respectively. These terminals in general continued to increase in number as the rats grew. Our results showed that BDNF immunoreactivity increased in various regions of the postnatally developing rat brain and suggest that BDNF might play an important role in neuronal maturation.