A Novel Chronic Enteropathy Associated with SLCO2A1 Gene Mutation: Enterography Findings in a Multicenter Korean Registry

Objective@#Chronic enteropathy associated with SLCO2A1 gene (CEAS) is a recently recognized disease. We aimed to evaluate the enterographic findings of CEAS. @*Materials and Methods@#Altogether, 14 patients with CEAS were confirmed based on known SLCO2A1 mutations. They were registered in a multicenter Korean registry between July 2018 and July 2021. Nine of the patients (37.2 ± 13 years; all female) who underwent surgery-naïve-state computed tomography enterography (CTE) or magnetic resonance enterography (MRE) were identified. Two experienced radiologists reviewed 25 and 2 sets of CTE and MRE examinations, respectively, regarding the small bowel findings. @*Results@#In initial evaluation, eight patients showed a total of 37 areas with mural abnormalities in the ileum on CTE, including 1–4 segments in six and > 10 segments in two patients. One patient showed unremarkable CTE. The involved segments were 10–85 mm (median, 20 mm) in length, 3–14 mm (median, 7 mm) in mural thickness, circumferential in 86.5% (32/37), and showed stratified enhancement in the enteric and portal phases in 91.9% (34/37) and 81.8% (9/11), respectively. Perienteric infiltration and prominent vasa recta were noted in 2.7% (1/37) and 13.5% (5/37), respectively. Bowel strictures were identified in six patients (66.7%), with a maximum upstream diameter of 31–48 mm. Two patients underwent surgery for strictures immediately after the initial enterography. Follow-up CTE and MRE in the remaining patients showed minimal-to-mild changes in the extent and thickness of the mural involvement for 17–138 months (median, 47.5 months) after initial enterography. Two patients required surgery for bowel stricture at 19 and 38 months of follow-up, respectively. @*Conclusion@#CEAS of the small bowel typically manifested on enterography in varying numbers and lengths of abnormal ileal segments that showed circumferential mural thickening with layered enhancement without perienteric abnormalities. The lesions caused bowel strictures that required surgery in some patients.

Interlaboratory Comparison Study (Ring Test) of Next-Generation Sequencing–Based NTRK Fusion Detection in South Korea / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Tropomyosin receptor kinase (TRK) inhibitors are approved for the treatment of neurotrophic receptor tyrosine kinase (NTRK) fusion-positive tumors. The detection of NTRK fusion using a validated method is required before therapeutic application. An interlaboratory comparison study of next-generation sequencing (NGS)–based NTRK gene fusion detection with validated clinical samples was conducted at six major hospitals in South Korea. @*Materials and Methods@#A total of 18 samples, including a positive standard reference and eight positive and nine negative clinical samples, were validated using the VENTANA pan-TRK (EPR17341) and TruSight Oncology 500 assays. These samples were then tested using four different NGS panels currently being used at the six participating institutions. @*Results@#NTRK fusions were not detected in any of the nine negative clinical samples, demonstrating 100% specificity in all six participating institutions. All assays showed 100% analytical sensitivity to identify the NTRK fusion status in formalin-fixed paraffin-embedded (FFPE) samples, although with variable clinical sensitivity. False-negative results were due to low tumor purity, poor RNA quality, and DNA-based sequencing panel. The RNA-based targeted NGS assay showed an overall high success rate of identifying NTRK fusion status in FFPE samples. @*Conclusion@#This study is the first to test the proficiency of NGS-based NTRK detection in South Korea with the largest participating institutions. RNA-based NGS assays to detect NTRK fusions can accurately characterize fusion transcripts if sufficient RNA of adequate quality is available. The comparative performance data will support the implementation of targeted NGS-based sequencing assays for NTRK fusion detection in routine diagnostics.

BRCA-mutated gastric adenocarcinomas are associated with chromosomal instability and responsiveness to platinum-based chemotherapy

Background@#Homologous recombination defect is an important biomarker of chemotherapy in certain tumor types, and the presence of pathogenic or likely pathogenic mutations involving BRCA1 or BRCA2 (p-BRCA) mutations is the most well-established marker for the homologous recombination defect. Gastric cancer, one of the most prevalent tumor types in Asia, also harbors p-BRCA mutations. @*Methods@#To investigate the clinical significance of p-BRCA mutations, we analyzed 366 gastric cancer cases through next-generation sequencing. We determined the zygosity of p-BRCA mutations based on the calculated tumor purity through variant allelic fraction patterns and investigated whether the presence of p-BRCA mutations is associated with platinum-based chemotherapy and a certain molecular subtype. @*Results@#Biallelic p-BRCA mutation was associated with better response to platinum-based chemotherapy than heterozygous p-BRCA mutation or wild type BRCA genes. The biallelic p-BRCA mutations was observed only in the chromosomal instability subtype, while all p-BRCA mutations were heterozygous in microsatellite instability subtype. @*Conclusions@#In conclusion, patients with gastric cancer harboring biallelic p-BRCA mutations were associated with a good initial response to platinum-based chemotherapy and those tumors were exclusively chromosomal instability subtype. Further investigation for potential association with homologous recombination defect is warranted.

A Study of Congenitally Missing Permanent Teeth in Wonju Severance Christian Hospital / 대한소아치과학회지

Congenitally missing teeth are one of the most prevalent dental anomalies in the oral cavity. In this study, the prevalence, distribution, and symmetry of congenitally missing permanent teeth among 1,865 patients aged 7 to 15 years who visited the Pediatric Dentistry Department of Wonju Severance Christian Hospital from March 2011 to May 2021 and took panoramic radiographs were investigated and analyzed. Most of the patients had one or two congenitally missing teeth, mainly in the second premolars and lateral incisors. Congenitally missing teeth occurred more in the mandible than in the maxilla, and there was no significant difference in prevalence between the left and right sides. Congenitally missing teeth tend to occur symmetrically on the left and right sides and in the maxilla and mandible, depending on the tooth. Early oral examination and radiological examination are required to prevent complications due to congenitally missing teeth, and appropriate interdisciplinary treatment is required.

Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group / Journal of the Korean Cancer Association, 대한암학회지

Next-generation sequencing (NGS) is becoming essential in the fields of precision oncology. With implementation of NGS in daily clinic, the needs for continued education, facilitated interpretation of NGS results and optimal treatment delivery based on NGS results have been addressed. Molecular tumor board (MTB) is multidisciplinary approach to keep pace with the growing knowledge of complex molecular alterations in patients with advanced solid cancer. Although guidelines for NGS use and MTB have been developed in western countries, there is limitation for reflection of Korea’s public health environment and daily clinical practice. These recommendations provide a critical guidance from NGS panel testing to final treatment decision based on MTB discussion.

Impact of COVID-19 on Dental Trauma in Korea / 대한소아치과학회지

The study was conducted to analyze the impacts of COVID-19 on the number of dental trauma patients. Based on the data provided by the Health Insurance Review and Assessment Service’s Healthcare Bigdata Hub, dental trauma which occurred from 2010 to 2020 was analyzed.Since the outbreak of COVID-19, the incidence of dental trauma per 100,000 decreased compared to the average Incidence between 2017 to 2019. By age, it decreased by 5.4% (p = 0.017) for 0 - 4 years old, 30.3% (p After the outbreak of COVID-19, the incidence of dental trauma decreased significantly for under 20 years old, but the decrease was not significant for 20 years old or older.

Extremely well-differentiated adenocarcinoma of the stomach: diagnostic pitfalls in endoscopic biopsy

Background@#Extremely well-differentiated adenocarcinoma (EWDA) is a deceptively bland-looking adenocarcinoma of the stomach. It often causes diagnostic problems, especially in endoscopic biopsy samples. To better recognize this deceptively bland lesion, we carefully reviewed a series of EWDAs treated at our institution. @*Methods@#A total of 55 specimens from 19 patients were obtained. Endoscopic, gross and microscopic features defining EWDA were described and documented. For comparison, hyperplastic polyp specimens were randomly selected and analyzed. @*Results@#Most cases (18 of 19, 94.7%) were advanced gastric cancer (AGC) and primarily located in the body of the stomach (15 of 19, 79.0%). The majority of AGCs were non-ulcerated (11 of 18, 61.1%) with an undermining growth pattern and a relatively small mucosal involvement. Specific histologic features included an irregular glandular shape, an undulating apical cytoplasmic border, disproportionately large glands, a variably distended mucinous cytoplasm. Classical features, such as small infiltrating glands or desmoplastic reactions, were barely observed. Identification of irregularly spaced nuclei and disruption of the foveolar epithelial structure, along with atypical features described above were helpful in making a diagnosis especially in gastric forceps biopsies. @*Conclusions@#Awareness of the histomorphologic characteristics described in this report would lead to timely diagnosis and prevent repeated endoscopic procedures.

How to Combine Diffusion-Weighted and T2-Weighted Imaging for MRI Assessment of Pathologic Complete Response to Neoadjuvant Chemoradiotherapy in Patients with Rectal Cancer?

Objective@#Adequate methods of combining T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) to assess complete response (CR) to chemoradiotherapy (CRT) for rectal cancer are obscure. We aimed to determine an algorithm for combining T2WI and DWI to optimally suggest CR on MRI using visual assessment. @*Materials and Methods@#We included 376 patients (male:female, 256:120; mean age ± standard deviation, 59.7 ± 11.1 years) who had undergone long-course CRT for rectal cancer and both pre- and post-CRT high-resolution rectal MRI during 2017– 2018. Two experienced radiologists independently evaluated whether a tumor signal was absent, representing CR, on both post-CRT T2WI and DWI, and whether the pre-treatment DWI showed homogeneous hyperintensity throughout the lesion. Algorithms for combining T2WI and DWI were as follows: ‘AND,’ if both showed CR; ‘OR,’ if any one showed CR; and ‘conditional OR,’ if T2WI showed CR or DWI showed CR after the pre-treatment DWI showed homogeneous hyperintensity. Their efficacies for diagnosing pathologic CR (pCR) were determined in comparison with T2WI alone. @*Results@#Sixty-nine patients (18.4%) had pCR. AND had a lower sensitivity without statistical significance (vs. 62.3% [43/69]; 59.4% [41/69], p = 0.500) and a significantly higher specificity (vs. 87.0% [267/307]; 90.2% [277/307], p = 0.002) than those of T2WI. Both OR and conditional OR combinations resulted in a large increase in sensitivity (vs. 62.3% [43/69]; 81.2% [56/69], p < 0.001; and 73.9% [51/69], p = 0.008, respectively) and a large decrease in specificity (vs. 87.0% [267/307]; 57.0% [175/307], p < 0.001; and 69.1% [212/307], p < 0.001, respectively) as compared with T2WI, ultimately creating additional false interpretations of CR more frequently than additional identification of patients with pCR. @*Conclusion@#AND combination of T2WI and DWI is an appropriate strategy for suggesting CR using visual assessment of MRI after CRT for rectal cancer.

Appendiceal actinomycosis mimicking appendiceal tumor, appendicitis or inflammatory bowel disease

Appendiceal actinomycosis is very rare and its diagnosis is often difficult even in surgically resected specimens. Here we report two cases of appendiceal actinomycosis confirmed by pathologic examination of surgically resected specimens. Characteristic histologic features included transmural chronic inflammation with Crohn-like lymphoid aggregates and polypoid mucosal protrusion into cecal lumen through fibrous expansion of the submucosa. Chronic active inflammation involved the mucosa of the appendix and cecum around the appendiceal orifice. Crohn’s disease with predominant cecal involvement and inflammatory pseudotumor were considered as differential diagnoses. Careful examination revealed a few actinomycotic colonies in the mucosa, confirming the diagnosis. A high index of suspicion with awareness of the characteristic histologic features might prompt careful inspection for the actinomycotic colonies, leading to the appropriate diagnosis of this rare disease.

Primary hepatic mixed germ cell tumor in an adult

Primary hepatic mixed germ cell tumor (GCT) is very rare, and less than 10 cases have been reported. We report a case of mixed GCT composed of a choriocarcinoma and yolk sac tumor, which occurred in the liver of a 40-year-old woman. A large mass was detected by computed tomography solely in the liver. Serum β-human chorionic gonadotropin (hCG) was highly elevated, otherwise, other serum tumor markers were slightly elevated or within normal limits. For hepatic choriocarcinoma, neoadjuvant chemotherapy was administered, followed by right lobectomy. Histologic features of the resected tumor revealed characteristic choriocarcinoma features with diffuse positivity for hCG in the syncytiotrophoblasts and diffuse positivity for α-fetoprotein and Sal-like protein 4 in the yolk sac tumor components. Primary malignant GCT in the liver is associated with a poor prognosis and requires specific treatment. Therefore, GCT should be considered during a differential diagnosis of a rapidly growing mass in the liver.

Standardization of the pathologic diagnosis of appendiceal mucinous neoplasms

Although the understanding of appendiceal mucinous neoplasms (AMNs) and their relationship with disseminated peritoneal mucinous disease have advanced, the diagnosis, classification, and treatment of AMNs are still confusing for pathologists and clinicians. The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists (GPSG-KSP) proposed a multicenter study and held a workshop for the “Standardization of the Pathologic Diagnosis of the Appendiceal Mucinous Neoplasm” to overcome the controversy and potential conflicts. The present article is focused on the diagnostic criteria, terminologies, tumor grading, pathologic staging, biologic behavior, treatment, and prognosis of AMNs and disseminated peritoneal mucinous disease. In addition, GPSG-KSP proposes a checklist of standard data elements of appendiceal epithelial neoplasms to standardize pathologic diagnosis. We hope the present article will provide pathologists with updated knowledge on how to handle and diagnose AMNs and disseminated peritoneal mucinous disease.

Acute Ileal Perforation Caused by Radiation Enteritis After Restoration

Few radiation-induced bowel perforations have been reported to date. Furthermore, perforation after ileal restoration in asymptomatic patients is rare. We report the case of a 61-year-old man who was administered preoperative chemoradiotherapy for advanced rectal cancer. The patient underwent ultra-low anterior resection with ileal diversion, followed by ileal restoration. Perforation was detected 9 days after restoration, and he underwent a right hemicolectomy. The histologic evaluation indicated ileal perforation caused by acute radiation enteritis.

How to Combine Diffusion-Weighted and T2-Weighted Imaging for MRI Assessment of Pathologic Complete Response to Neoadjuvant Chemoradiotherapy in Patients with Rectal Cancer?

Objective@#Adequate methods of combining T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) to assess complete response (CR) to chemoradiotherapy (CRT) for rectal cancer are obscure. We aimed to determine an algorithm for combining T2WI and DWI to optimally suggest CR on MRI using visual assessment. @*Materials and Methods@#We included 376 patients (male:female, 256:120; mean age ± standard deviation, 59.7 ± 11.1 years) who had undergone long-course CRT for rectal cancer and both pre- and post-CRT high-resolution rectal MRI during 2017– 2018. Two experienced radiologists independently evaluated whether a tumor signal was absent, representing CR, on both post-CRT T2WI and DWI, and whether the pre-treatment DWI showed homogeneous hyperintensity throughout the lesion. Algorithms for combining T2WI and DWI were as follows: ‘AND,’ if both showed CR; ‘OR,’ if any one showed CR; and ‘conditional OR,’ if T2WI showed CR or DWI showed CR after the pre-treatment DWI showed homogeneous hyperintensity. Their efficacies for diagnosing pathologic CR (pCR) were determined in comparison with T2WI alone. @*Results@#Sixty-nine patients (18.4%) had pCR. AND had a lower sensitivity without statistical significance (vs. 62.3% [43/69]; 59.4% [41/69], p = 0.500) and a significantly higher specificity (vs. 87.0% [267/307]; 90.2% [277/307], p = 0.002) than those of T2WI. Both OR and conditional OR combinations resulted in a large increase in sensitivity (vs. 62.3% [43/69]; 81.2% [56/69], p < 0.001; and 73.9% [51/69], p = 0.008, respectively) and a large decrease in specificity (vs. 87.0% [267/307]; 57.0% [175/307], p < 0.001; and 69.1% [212/307], p < 0.001, respectively) as compared with T2WI, ultimately creating additional false interpretations of CR more frequently than additional identification of patients with pCR. @*Conclusion@#AND combination of T2WI and DWI is an appropriate strategy for suggesting CR using visual assessment of MRI after CRT for rectal cancer.

Appendiceal actinomycosis mimicking appendiceal tumor, appendicitis or inflammatory bowel disease

Appendiceal actinomycosis is very rare and its diagnosis is often difficult even in surgically resected specimens. Here we report two cases of appendiceal actinomycosis confirmed by pathologic examination of surgically resected specimens. Characteristic histologic features included transmural chronic inflammation with Crohn-like lymphoid aggregates and polypoid mucosal protrusion into cecal lumen through fibrous expansion of the submucosa. Chronic active inflammation involved the mucosa of the appendix and cecum around the appendiceal orifice. Crohn’s disease with predominant cecal involvement and inflammatory pseudotumor were considered as differential diagnoses. Careful examination revealed a few actinomycotic colonies in the mucosa, confirming the diagnosis. A high index of suspicion with awareness of the characteristic histologic features might prompt careful inspection for the actinomycotic colonies, leading to the appropriate diagnosis of this rare disease.

Primary hepatic mixed germ cell tumor in an adult

Primary hepatic mixed germ cell tumor (GCT) is very rare, and less than 10 cases have been reported. We report a case of mixed GCT composed of a choriocarcinoma and yolk sac tumor, which occurred in the liver of a 40-year-old woman. A large mass was detected by computed tomography solely in the liver. Serum β-human chorionic gonadotropin (hCG) was highly elevated, otherwise, other serum tumor markers were slightly elevated or within normal limits. For hepatic choriocarcinoma, neoadjuvant chemotherapy was administered, followed by right lobectomy. Histologic features of the resected tumor revealed characteristic choriocarcinoma features with diffuse positivity for hCG in the syncytiotrophoblasts and diffuse positivity for α-fetoprotein and Sal-like protein 4 in the yolk sac tumor components. Primary malignant GCT in the liver is associated with a poor prognosis and requires specific treatment. Therefore, GCT should be considered during a differential diagnosis of a rapidly growing mass in the liver.

Standardization of the pathologic diagnosis of appendiceal mucinous neoplasms

Although the understanding of appendiceal mucinous neoplasms (AMNs) and their relationship with disseminated peritoneal mucinous disease have advanced, the diagnosis, classification, and treatment of AMNs are still confusing for pathologists and clinicians. The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists (GPSG-KSP) proposed a multicenter study and held a workshop for the “Standardization of the Pathologic Diagnosis of the Appendiceal Mucinous Neoplasm” to overcome the controversy and potential conflicts. The present article is focused on the diagnostic criteria, terminologies, tumor grading, pathologic staging, biologic behavior, treatment, and prognosis of AMNs and disseminated peritoneal mucinous disease. In addition, GPSG-KSP proposes a checklist of standard data elements of appendiceal epithelial neoplasms to standardize pathologic diagnosis. We hope the present article will provide pathologists with updated knowledge on how to handle and diagnose AMNs and disseminated peritoneal mucinous disease.

Acute Ileal Perforation Caused by Radiation Enteritis After Restoration

Few radiation-induced bowel perforations have been reported to date. Furthermore, perforation after ileal restoration in asymptomatic patients is rare. We report the case of a 61-year-old man who was administered preoperative chemoradiotherapy for advanced rectal cancer. The patient underwent ultra-low anterior resection with ileal diversion, followed by ileal restoration. Perforation was detected 9 days after restoration, and he underwent a right hemicolectomy. The histologic evaluation indicated ileal perforation caused by acute radiation enteritis.

Analysis of the Characteristics of Children and Adolescent Patients Received Sealant after National Health Insurance Coverage using Big Data / 대한소아치과학회지

The purpose of this study was to analyze the characteristics of pediatric and adolescent patients who received sealant after health insurance coverage based on demographic factors such as gender, age, insurance type, care institution and region.Patient Sample Data from the Health Insurance Review and Assessment Service were used for this study. A total of 8,454,636 patients’ data were obtained from 2010 to 2017. Of these, 114,680 patients got sealant treatment. Females were more likely to receive sealant treatment than males. 5 - 9 year age group showed the highest number of patients and proportion of treatment. Patients with health insurance were more likely to receive pit and fissure sealant treatment compared to patients with medical aid program. The number of sealant patients and the proportion of sealant treatment were the highest in dental clinics, followed by dental hospitals and public health centers. The number of sealant patients were the highest in Gyeonggi and proportion of sealant patients were the highest in Jeonbuk.

Analysis of the Association between COVID-19 and Dental Visits inChildren and Adolescents through Big Data / 대한소아치과학회지

This study was conducted to investigate changes in dental visits in children and adolescents due to COVID-19. Based on the data provided by the Korea Health Insurance Review and Assessment Service, the number of dental visits among children and adolescents from January 2019 to August 2020, and the rate change according to Korean disease classification in 2019 and 2020 were analyzed by month and region. From January to August 2020, compared to the same period in 2019, the total number of visits to dental clinics and dental hospitals among children and adolescents decreased by 642,202 times (16.3%) in the 0 - 9 years old group, and 313,488 times (9.2%) in the 10 - 19 years old group. During the same period, the decreases due to Z29 (Need for other prophylactic measures) decreased by 118,219 times (34%) in the 0 - 9 years old group and 83,944 times (31%) in the 10 - 19 years old group, showing the greatest change. It is analyzed that overall dental service of children and adolescents has decreased due to COVID-19, and this may lead to deterioration of oral health of children and adolescents in the future, and this study can be used as a reference in case of an infectious disease such as COVID-19 in the future.

Sarcoma metastasis to the pancreas: experience at a single institution

Background@#Reports of metastatic sarcoma to the pancreas are limited. We reviewed the clinicopathologic characteristics of such cases. @*Methods@#We reviewed 124 cases of metastatic tumors to the pancreas diagnosed at Asan Medical Center between 2000 and 2017. @*Results@#Metastatic tumors to the pancreas consisted of 111 carcinomas (89.5%), 12 sarcomas (9.6%), and one melanoma (0.8%). Primary sarcoma sites were bone (n = 4); brain, lung, and soft tissue (n = 2 for each); and the uterus and pulmonary vein (n = 1 for each). Pathologically, the 12 sarcomas comprised 2 World Health Organization grade III solitary fibrous tumors/hemangiopericytomas, and one case each of synovial sarcoma, malignant solitary fibrous tumor, undifferentiated pleomorphic sarcoma, osteosarcoma, mesenchymal chondrosarcoma, intimal sarcoma, myxofibrosarcoma, myxoid liposarcoma, rhabdomyosarcoma, subtype uncertain, and high-grade spindle-cell sarcoma of uncertain type. The median interval between primary cancer diagnosis and pancreatic metastasis was 28.5 months. One case manifested as a solitary pancreatic osteosarcoma metastasis 15 months prior to detection of osteosarcoma in the femur and was initially misdiagnosed as sarcomatoid carcinoma of the pancreas. @*Conclusions@#The metastatic sarcoma should remain a differential diagnosis when spindle-cell malignancy is found in the pancreas, even for solitary lesions or in patients without prior history.