Background/Aims: The prospective Crohn’s Disease Clinical Network and Cohort Study is a nationwide multicenter cohort study of patients with Crohn’s disease (CD) in Korea, aiming to prospectively investigate the clinical features and long-term prognosis associated with CD. Methods: Patients diagnosed with CD between January 2009 and September 2019 were prospectively enrolled. They were divided into two cohorts according to the year of diagnosis: cohort 1 (diagnosed between 2009 and 2011) versus cohort 2 (between 2012 and 2019). Results: A total of 1,175 patients were included, and the median follow-up duration was 68 months (interquartile range, 39.0 to 91.0 months). The treatment-free durations for thiopurines (p<0.001) and anti-tumor necrosis factor agents (p=0.018) of cohort 2 were shorter than those of cohort 1. Among 887 patients with B1 behavior at diagnosis, 149 patients (16.8%) progressed to either B2 or B3 behavior during follow-up. Early use of thiopurine was associated with a reduced risk of behavioral progression (adjusted hazard ratio [aHR], 0.69; 95% confidence interval [CI], 0.50 to 0.90), and family history of inflammatory bowel disease was associated with an increased risk of behavioral progression (aHR, 2.29; 95% CI, 1.16 to 4.50). One hundred forty-one patients (12.0%) underwent intestinal resection, and the intestinal resection-free survival time was significantly longer in cohort 2 than in cohort 1 (p=0.003). The early use of thiopurines (aHR, 0.35;95% CI, 0.23 to 0.51) was independently associated with a reduced risk of intestinal resection. Conclusions The prognosis of CD in Korea appears to have improved over time, as evidenced by the decreasing intestinal resection rate. Early use of thiopurines was associated with an improved prognosis represented by a reduced risk of intestinal resection.

Traditionally, urologists recommend an interval of at least 4 weeks after prostate biopsy before radical prostatectomy. The aim of our study was to evaluate whether the interval from prostate biopsy to radical prostatectomy affects immediate operative outcomes, with a focus on differences in surgical approach. The study population of 1,848 radical prostatectomy patients was divided into two groups according to the surgical approach: open or minimally invasive. Open group included perineal and retropubic approach, and minimally invasive group included laparoscopic and robotic approach. The cut-off of the biopsy-to-surgery interval was 4 weeks. Positive surgical margin status, operative time and estimated blood loss were evaluated as endpoint parameters. In the open group, there were significant differences in operative time and estimated blood loss between the <4-week and > or =4-week interval subgroups, but there was no difference in positive margin rate. In the minimally invasive group, there were no differences in the three outcome parameters between the two subgroups. Multivariate analysis revealed that the biopsy-to-surgery interval was not a significant factor affecting immediate operative outcomes in both open and minimally invasive groups, with the exception of the interval > or =4 weeks as a significant factor decreasing operative time in the minimally invasive group. In conclusion, performing open or minimally invasive radical prostatectomy within 4 weeks of prostate biopsy is feasible for both approaches, and is even beneficial for minimally invasive radical prostatectomy to reduce operative time.
Humans ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures/*statistics & numerical data ; *Operative Time ; Postoperative Hemorrhage/*epidemiology ; Prevalence ; Prostatectomy/*statistics & numerical data ; Prostatic Neoplasms/epidemiology/*pathology/*surgery ; Republic of Korea/epidemiology ; Retrospective Studies ; Time-to-Treatment/*statistics & numerical data ; Treatment Outcome

Malignant glioma is the most frequent type in brain tumors. The prognosis of this tumor has not been significantly improved for the past decades and the average survival of patients is less than one year. Thus, an effective novel therapy is urgently needed. TNF-related apoptosis inducing ligand (TRAIL), known to have tumor cell-specific killing activity, has been investigated as a novel therapeutic for cancers. We have developed Ad-stTRAIL, an adenovirus delivering secretable trimeric TRAIL for gene therapy and demonstrated the potential to treat malignant gliomas. Currently, this Ad-stTRAIL gene therapy is under phase I clinical trial for malignant gliomas. Here, we report preclinical studies for Ad-stTRAIL carried out using rats. We delivered Ad-stTRAIL intracranially and determined its pharmacokinetics and biodistribution. Most Ad-stTRAIL remained in the delivered site and the relatively low number of viral genomes was detected in the opposite site of brain and cerebrospinal fluid. Similarly, only small portion of the viral particles injected was found in the blood plasma and major organs and tissues, probably due to the brain-blood barrier. Multiple administrations did not lead to accumulation of Ad-stTRAIL at the injection site and organs. Repeated delivery of Ad-stTRAIL did not show any serious side effects. Our data indicate that intracranially delivered Ad-stTRAIL is a safe approach, demonstrating the potential as a novel therapy for treating gliomas.
Adenoviridae/genetics ; Animals ; Blood-Brain Barrier ; Brain/drug effects/*metabolism/pathology ; Brain Neoplasms/genetics/metabolism/pathology/*therapy ; Clinical Trials, Phase I as Topic ; DNA, Viral/metabolism ; Disease Models, Animal ; Drug Delivery Systems ; Drug Evaluation, Preclinical ; *Gene Therapy ; Glioma/genetics/metabolism/pathology/*therapy ; Humans ; Liver/drug effects/metabolism/pathology ; Protein Multimerization/genetics ; Rats ; Spleen/drug effects/metabolism/pathology ; TNF-Related Apoptosis-Inducing Ligand/genetics/*pharmacokinetics

Malignant glioma is the most frequent type in brain tumors. The prognosis of this tumor has not been significantly improved for the past decades and the average survival of patients is less than one year. Thus, an effective novel therapy is urgently needed. TNF-related apoptosis inducing ligand (TRAIL), known to have tumor cell-specific killing activity, has been investigated as a novel therapeutic for cancers. We have developed Ad-stTRAIL, an adenovirus delivering secretable trimeric TRAIL for gene therapy and demonstrated the potential to treat malignant gliomas. Currently, this Ad-stTRAIL gene therapy is under phase I clinical trial for malignant gliomas. Here, we report preclinical studies for Ad-stTRAIL carried out using rats. We delivered Ad-stTRAIL intracranially and determined its pharmacokinetics and biodistribution. Most Ad-stTRAIL remained in the delivered site and the relatively low number of viral genomes was detected in the opposite site of brain and cerebrospinal fluid. Similarly, only small portion of the viral particles injected was found in the blood plasma and major organs and tissues, probably due to the brain-blood barrier. Multiple administrations did not lead to accumulation of Ad-stTRAIL at the injection site and organs. Repeated delivery of Ad-stTRAIL did not show any serious side effects. Our data indicate that intracranially delivered Ad-stTRAIL is a safe approach, demonstrating the potential as a novel therapy for treating gliomas.
Adenoviridae/genetics ; Animals ; Blood-Brain Barrier ; Brain/drug effects/*metabolism/pathology ; Brain Neoplasms/genetics/metabolism/pathology/*therapy ; Clinical Trials, Phase I as Topic ; DNA, Viral/metabolism ; Disease Models, Animal ; Drug Delivery Systems ; Drug Evaluation, Preclinical ; *Gene Therapy ; Glioma/genetics/metabolism/pathology/*therapy ; Humans ; Liver/drug effects/metabolism/pathology ; Protein Multimerization/genetics ; Rats ; Spleen/drug effects/metabolism/pathology ; TNF-Related Apoptosis-Inducing Ligand/genetics/*pharmacokinetics

The life cycle of Fibricola seoulensis was studied in the laboratory and in the field, with special interests in the larval developments within the eggs and in the intermediate hosts. The first emergence of miracidia after incubation of eggs in 26C water began on the ninth day. The miracidia, elongate and cylindrical shape, had epidermal plates in the formula of 6, 9, 4 and 3, with two pairs of flame cells and lateral processes. A kind of fresh water snail, Hippeutis (H.) cantori, was found to shed furcocercous cercariae from the 13th day after experimental challenge with miracidia while Physa acuta failed to shed. The same kind of snail collected from the field also shed the same cercariae. The cercariae were equipped with 2 pairs of penetration glands and 5 pairs of flame cells. The tadpoles of Rana nigromaculata were found susceptible to experimental infection with the cercariae. The same kind of tadpoles collected from various areas were also found naturally infected. The metacercariae in the tadpoles which were infected experimentally became infective to the definitive host in 21 days. The metacercariae were located free in the body cavity of tadpoles, and attained sexual maturity in rats in 7 days. The present study successfully followed the complete life cycle of F. seoulenis and found that it is possible to maintain the life cycle in the laboratory.
parasitology-helminth-termatoda ; Fibricola seoulensis ; biology ; rat ; Hippeutis cantori ; Rana nigromaculata ; Physa acuta ; intermediate host

A human case of Centrocestus armatus (Heterophyidae) infection was proved by identifying an adult worm collected after treatment with praziquantel in Korea. The case is 42-year old man who resides in a rural area in Sanchung-gun, Kyeongsangnam-do. The case was concomitantly infected with Clonorchis sinensis and had the history of eating raw freshwater fishes including Zacco platypus, which are known to be the second intermediate host of C. armatus in Korea.. This is the first report of natural human infection by C. armatus in the literature.
parasitology-helminth-trematoda ; Centrocestus armatus ; intestine ; Heterophyidae ; Clonorchis sinensis ; case report

Two adult specimens of heterophyid fluke, which belong to the genus Stictodora, were collected from the stool of a 24-year old man after chemotherapy. The flukes were morphologically characterized by their small body size (0.90~0.98 mm long and 0.38 mm wide) and peculiar structure of ventrogenital sac with armed gonotyl (with about 12~15 spines) not enveloping genital pore. Species identification is deferred until more worms are obtained, although they closely resemble Stictodora fuscatum (Onji and Nishio, 1916). The patient used to eat raw flesh of mullets and gobies, which are regarded as the infection source of Stictodora sp., together with 3 other kinds of heterophyids described elsewhere. This is the first record of human Stictodora infection in the literature.
parasitology-helminth-trematoda ; case report ; Stictodora sp. ; Heterophyidae ; intestine

This study was carried out to reveal the effect of temperature, salinity and aeration on maturation and hatching of Fibricola seoulensis eggs. The eggs were incubated and were observed daily for the appearance of eyespots and hatching. The results were summerized as follows: From 4-5 days after incubation in distilled water at 28C or at 11-26C, the eyespots began to appear and the rate of eggs with eyespots were over 90% in 28C on the 7th or 8th day. However, eyespots did not appear in 5-15C or 4C by the 18th day. The mature eggs began to hatch at the 8th day, and hatching rate 2 weeks after incubation was over 90% at 28C, but it was below 5% at 11-26C, and 0% at 5-15C and 4C. Aeration did not influence the appearance of eyespots nor hatching. In saline under 0.6%, the rates of eyespots were over 90% on the 7th day. The rate was 55.0% in 0.9% at 20 days, and 0% in 1.2%. The hatching rates in salines below 0.3% concentration were over 90% by 14 days of incubation. However, the rate decreased to 44% in 0.6% saline and to 0% over 0.9% salinity. The eggs incubated in the dark hatched in 12.5% on the 10th day, but hatching rate of maturation eggs increased to 85.7% within 2 hours after exposure to light. Above results demonstrated that the best temperature for maturation and hatching of F. seoulensis eggs was 28C, and the miracidia began to hatch at 8-9 days after incubation. In the field hatching and invasion into snails of the miracidia may occur from May to September in Korea. In salines under 0.3 percent concentration maturation and hatching were not influenced, but as salinity increased hatching was inhibited more than maturation was.
parasitology-helminth-trematoda ; Fibricola seoulensis ; metacercaria ; development ; egg ; saline

In order to observe the growth and development of Fibricola seoulensis metacercariae, the tadpoles of Rana nigromagulata were experimentally infected with the cercariae. The metacercariae of various developmental stages were recovered from the tadpoles after 2 to 65 days of infection. They were prepared for morphological observation, and were given orally to mice to observe their infectivity. The following results were obtained. All of the tadpoles exposed to the cercariae were observed to harbour the larvae in their abdominal cavity. The young metacercariae of 2 days after infection were 121.1 micrometer long and 63.3 micrometer wide. They grow linearly for the first 14 days to be 262.0 micrometer long and 166.4 micrometer wide. Thereafter, no more growth recognized until 65 days. The larvae of 2 days old were similar with cercarial body and had 2 suckers, a pharynx, two ceca and a primordium of germ cells but no tribocytic organ. On the 8th day, they had tribocytic organ, and their morphology resembled that of mature metacercariae. The metacercariae younger than 10 days could not infect the mice. Only the metacercariae older than 14 days had infectivity. The recovery rate increased by the age of metacercariae from 19.0% in 14 days old to 70.0% in 40 days old. Above findings indicate that the tadpole is indispensible for metacercarial development and it needs at least 2 weeks for maturation. The tadpole is a pivotal host in the life cycle of F. seoulensis for connection between the snail and the frog.
parasitology-helminth-trematoda ; Fibricola seoulensis ; metacercaria ; development

Two human cases of Heterophyes heterophyes and H. dispar infections were proven by the recovery of their adult worms. The cases were 38-year and 40-year old Korean workers who had been in Saudi Arabia for 4-6 years and returned home in 1983 or 1984 with gastrointestinal troubles. In Saudi Arabia they had eaten raw brackish water fishes such as the mullet. After the treatment with 10 mg/kg praziquantel and purgation with magnesium salt, a total of 19 specimens of H.heterophyes and 140 of H. dispar were collected. It is of interest that the worms persisted in a patient although he had been back in Korea for 14 months. This is the first report on imported heterophyiasis in Korea. Human infection by H. dispar is the first record in the literature.
parasitology-helminth-trematoda ; Heterophyes heterophyes ; Heterophyes dispar ; case report ; praziquantel ; intestine