Korean Practice Guidelines for Gastric Cancer 2022: An Evidence-based, Multidisciplinary Approach

Gastric cancer is one of the most common cancers in Korea and the world. Since 2004, this is the 4th gastric cancer guideline published in Korea which is the revised version of previous evidence-based approach in 2018. Current guideline is a collaborative work of the interdisciplinary working group including experts in the field of gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology and guideline development methodology. Total of 33 key questions were updated or proposed after a collaborative review by the working group and 40 statements were developed according to the systematic review using the MEDLINE, Embase, Cochrane Library and KoreaMed database. The level of evidence and the grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation proposition. Evidence level, benefit, harm, and clinical applicability was considered as the significant factors for recommendation. The working group reviewed recommendations and discussed for consensus. In the earlier part, general consideration discusses screening, diagnosis and staging of endoscopy, pathology, radiology, and nuclear medicine. Flowchart is depicted with statements which is supported by meta-analysis and references. Since clinical trial and systematic review was not suitable for postoperative oncologic and nutritional follow-up, working group agreed to conduct a nationwide survey investigating the clinical practice of all tertiary or general hospitals in Korea. The purpose of this survey was to provide baseline information on follow up. Herein we present a multidisciplinary-evidence based gastric cancer guideline.

A Standardized Pathology Report for Gastric Cancer: 2nd Edition

The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements.The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.

A standardized pathology report for gastric cancer: 2nd edition

The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.

Improved anti-fibrotic effects by combined treatments of simvastatin and NS-398 in experimental liver fibrosis models

Background/Aims@#Efficient anti-fibrotic therapies are required for the treatment of liver cirrhosis. Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and cyclooxygenase-2 (COX-2) inhibitors have been reported to have anti-fibrotic effects. Here, we investigated whether combined treatment with a statin and a COX-2 inhibitor has synergistic anti-fibrotic effects. @*Methods@#The effects of treatment strategies incorporating both simvastatin and a COX-2 inhibitor, NS-398, were investigated using an immortalized human hepatic stellate cell line (LX-2) and a hepatic fibrosis mouse model developed using thioacetamide (TAA) in drinking water. Cellular proliferation was investigated via 5-bromo-2-deoxyuridine uptake. Pro- and anti-apoptotic factors were investigated through Western blotting and real-time polymerase chain reaction analysis. @*Results@#The evaluation of the anti-proliferative effects on LX-2 cells showed that the observed effects were more pronounced with combination therapy than with single-drug therapy. Moreover, hepatic fibrosis and collagen deposition decreased significantly in TAA-treated mice in response to the combined treatment strategy. The mechanisms underlying the anti-fibrotic effects of the combination therapy were investigated. The effects of the combination therapy were correlated with increased expression levels of extracellular signal-regulated kinase 1/2 signaling molecules, upregulation of the Bax/Bcl-2 signaling pathway, inhibition of the transforming growth factor-β signaling pathway, and inhibition of tissue inhibitor of matrix metalloproteinases 1 and 2. @*Conclusions@#The combination of simvastatin and NS-398 resulted in a synergistic anti-fibrotic effect through multiple pathways. These findings offer a theoretical insight into the possible clinical application of this strategy for the treatment of advanced liver diseases with hepatic fibrosis.

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.

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.

Standardized Pathology Report for Colorectal Cancer, 2nd Edition

The first edition of the ‘Standardized Pathology Report for Colorectal Cancer,’ which was developed by the Gastrointestinal Pathology Study Group (GIP) of the Korean Society of Pathologists, was published 13 years ago. Meanwhile, there have been many changes in the pathologic diagnosis of colorectal cancer (CRC), pathologic findings included in the pathology report, and immunohistochemical and molecular pathology required for the diagnosis and treatment of colorectal cancer. In order to reflect these changes, we (GIP) decided to make the second edition of the report. The purpose of this standardized pathology report is to provide a practical protocol for Korean pathologists, which could help diagnose and treat CRC patients. This report consists of “standard data elements” and “conditional data elements.” Basic pathologic findings and parts necessary for prognostication of CRC patients are classified as “standard data elements,” while other prognostic factors and factors related to adjuvant therapy are classified as “conditional data elements” so that each institution could select the contents according to the characteristics of the institution. The Korean version is also provided separately so that Korean pathologists can easily understand and use this report. We hope that this report will be helpful in the daily practice of CRC diagnosis.

Undifferentiated Carcinoma with Osteoclast-Like Giant Cells of the Pancreas Mimicking a Predominantly Calcified Mass: Case Report and Literature Review

Undifferentiated carcinoma with osteoclast-like giant cells (UCOGCs) of the pancreas is a rare neoplasm that contains osteoclast-like giant cells, which are morphologically identical to those seen in giant cell tumors of bones. Histopathologically, it is composed of round to spindle-shaped neoplastic cells and non-neoplastic histiocytic giant cells. Although only limited radiologic findings are available due to the rarity of this tumor, UCOGCs shows variable imaging features in the literature from an inhomogeneous solid mass to a multilocular cystic tumor. Herein, we report an unusual manifestation of UCOGCs of the pancreas mimicking a predominantly calcified mass with radiologic-pathologic correlation.

Clinical significance of pancreatic intraepithelial neoplasia in resectable pancreatic cancer on survivals

PURPOSE: Noninvasive precursor lesions for pancreatic adenocarcinoma include pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm. PanIN is often found synchronously adjacent to resected pancreatic ductal adenocarcinoma (PDAC) tumors. However, its prognostic significance on outcome after PDAC resection is unknown. The purpose of the current study was to determine if the presence of PanIN has a prognostic or predictive effect on survival after resection for PDAC with curative intent. METHODS: We retrospectively reviewed the clinicopathologic data of patients who underwent pancreatectomy for PDAC from January 2002 to January 2013. Intraductal papillary mucinous lesions and mucinous cystic neoplasms were excluded. All available postoperative imaging and clinical follow-up data were reviewed. RESULTS: There were 95 patients who underwent pancreatectomy. Tumors were most commonly located in the pancreas head and as such pancreaticoduodenectomy was the most commonly performed operation. The median tumor size was 3.2 cm. An absence of PanIN lesions was identified in 39 patients (41%). Of the patients with PanIN lesions, high-grade PanIN (grade 3) was the most common type (64.3%) followed by grade 2 (28.6%). There was no significant difference in overall survival or disease-free survival between the non-PanIN and PanIN groups. CONCLUSION: The presence or absence of PanIN lesions did not affect survival in patients undergoing resection for pancreatic cancer. However, patients with high-grade PanINs tended to have better overall survival. Larger studies with longer follow up are needed to accurately determine its clinical significance.

The General Rules for the Study of Primary Liver Cancer

The General Rules for the Study of Primary Liver Cancer was published in June 2001 as the first edition. Since then, the 5th edition of the General Rules for the Study of Primary Liver Cancer was published by the 17th Committee of the Korean Liver Cancer Association based on the most recent data. The 5th edition of the General Rules for the Study of Primary Liver Cancer ranged over numerous topics such as anatomy, medical assessment of the patients, staging of hepatocellular carcinoma, description of the image findings, summary of hepatic resection, description of the surgical specimens, liver transplantation, reporting the pathological findings, pathological examinations of liver specimen, non-surgical treatment, radiotherapy, and assessment of tumor response after non-surgical treatment of hepatocellular carcinoma. The 5th General Rules for the Study of Primary Liver Cancer will not only become the basis of academic development for liver cancer studies in Korea, but also serve as the primary form of national liver cancer data accumulation based on standardized rules.

Epithelioid angiomyolipoma of the liver: a case report

Epithelioid angiomyolipoma (EAML) of liver is a rare neoplasm. Hepatic EAML is often misdiagnosed as other neoplasms such as hepatocellular carcinoma due to non-specific clinical and radiologic features. The morphologic features under microscope and immunohistochemistry staining profile are important in the diagnosis EAML. Here, we report a case of 52-year-old man who found 1.2 cm mass in liver by routine checkup. On the impression of hepatocellular carcinoma, lateral sectionectomy of the liver was done. Microscopically, the tumor is composed of predominant epithelioid cells with vascular component and foamy cells. These cells were positive for HMB45, MelanA, and smooth muscle actin and negative for epithelial membrane antigen. The final diagnosis was hepatic EAML.

Complete response of advanced hepatocellular carcinoma to sorafenib: another case and a comprehensive review

Since sorafenib was introduced in 2007 for treating advanced hepatocellular carcinoma (HCC), 15 patients have achieved a complete response (CR) in advanced HCC. However, only four of these reports can be regarded as real CRs involving adequate assessments including imaging, serum tumor markers, and histologic examinations of completely resected specimens. A 54-year-old man with hepatitis C virus (HCV)-related liver cirrhosis (LC) presented to our unit. A CT scan demonstrated a 3.8-cm arterial hypervascular/portal-washout mass in the right lobe and invasion in the right portal vein. Twelve weeks after beginning sorafenib therapy, the AFP level was normalized and a CT scan showed a prominent decrease in the hepatic mass and a significant decrease in the volume of portal vein thrombosis (PVT). The patient received a right liver hemihepatectomy after 12 months. No viable tumor cells were found in the resected specimen, and there was no thrombotic obstruction of the portal vein. Twelve months later the patient showed no clinical evidence of HCC recurrence. This is the first case of CR in HCC treatment following sorafenib with histologically confirmed HCV-related HCC without LC evidence, HCC with PVT, and a follow-up of longer than 12 months. This case seems to be an extremely unusual clinical outcome in advanced HCC.

SIRT7, H3K18ac, and ELK4 Immunohistochemical Expression in Hepatocellular Carcinoma

BACKGROUND: SIRT7 is one of the histone deacetylases and is NAD-dependent. It forms a complex with ETS-like transcription factor 4 (ELK4), which deacetylates H3K18ac and works as a transcriptional suppressor. Overexpression of SIRT7 and deacetylation of H3K18ac have been shown to be associated with aggressive clinical behavior in some cancers, including hepatocellular carcinoma (HCC). The present study investigated the immunohistochemical expression of SIRT7, H3K18ac, and ELK4 in hepatocellular carcinoma. METHODS: A total of 278 HCC patients were enrolled in this study. Tissue microarray blocks were made from existing paraffin-embedded blocks. Immunohistochemical expressions of SIRT7, H3K18ac and ELK4 were scored and analyzed. RESULTS: High SIRT7 (p = .034), high H3K18ac (p = .001), and low ELK4 (p = .021) groups were associated with poor outcomes. Age < 65 years (p = .028), tumor size ≥ 5 cm (p = .001), presence of vascular emboli (p = .003), involvement of surgical margin (p = .001), and high American Joint Committee on Cancer stage (III&V) (p < .001) were correlated with worse prognoses. In multivariate analysis, H3K18ac (p = .001) and ELK4 (p = .015) were the significant independent prognostic factors. CONCLUSIONS: High SIRT7 expression with poor overall survival implies that deacetylation of H3K18ac contributes to progression of HCC. High H3K18ac expression with poor prognosis is predicted due to a compensation mechanism. In addition, high ELK4 expression with good prognosis suggests another role of ELK4 as a tumor suppressor beyond SIRT7's helper. In conclusion, we could assume that the H3K18ac deacetylation pathway is influenced by many other factors.

Hornerin Is Involved in Breast Cancer Progression / 한국유방암학회지

PURPOSE: The S100 gene family, which comprises over 20 members, including S100A1, S100A2, S100A8, S100A9, profilaggrin, and hornerin encodes low molecular weight calcium-binding proteins with physiological and pathological roles in keratinization. Recent studies have suggested a link between S100 proteins and human cancer progression. The purpose of the present study was to determine the expression levels of hornerin, S100A8, and S100A9 and evaluate their roles in the progression of invasive ductal carcinoma (IDC). METHODS: Seventy cases of ductal carcinoma in situ (DCIS), IDC, and metastatic carcinoma in lymph nodes (MCN) were included. Tissue microarrays were constructed from lesions of DCIS, IDC, and MCN from the same patients. Expression of hornerin, S100A8, and S100A9 was analyzed using immunohistochemistry. RESULTS: The expression of hornerin was associated with the estrogen receptor-negative (p=0.003) and the human epidermal growth factor receptor 2-positive (p=0.002) groups. The expression of S100A8 was associated with a higher pT stage (p=0.017). A significant (p0.050) different. The expression of hornerin increased in a stepwise manner (DCIS

Hypothalamic Extraventricular Neurocytoma (EVN) in a Pediatric Patient: A Case of EVN Treated with Subtotal Removal Followed by Adjuvant Radiotherapy

Extra ventricular neurocytoma (EVN) is a rare brain tumor with histologic features similar with a central neurocytoma, but located outside of the ventricular system. In this study, we present an unusual case of hypothalamic EVN in a 14-year-old patient. The patient underwent subtotal removal and had tumor relapse. The patient was then treated using intensity modulated radiation therapy, and the tumor remained stable for 24 months. This case report may be important in that this is the first pediatric case of EVN located in the hypothalamic region. EVN has similar radiologic features with pilocytic astrocytomas and therefore a hypothalamic EVN may be misdiagnosed as a hypothalamic glioma. Also, the pathologic-radiologic-clinical correlation of EVN located in the hypothalamic area may be different from that of EVNs originating from other usual sites.

Hypothalamic Extraventricular Neurocytoma (EVN) in a Pediatric Patient: A Case of EVN Treated with Subtotal Removal Followed by Adjuvant Radiotherapy

Extra ventricular neurocytoma (EVN) is a rare brain tumor with histologic features similar with a central neurocytoma, but located outside of the ventricular system. In this study, we present an unusual case of hypothalamic EVN in a 14-year-old patient. The patient underwent subtotal removal and had tumor relapse. The patient was then treated using intensity modulated radiation therapy, and the tumor remained stable for 24 months. This case report may be important in that this is the first pediatric case of EVN located in the hypothalamic region. EVN has similar radiologic features with pilocytic astrocytomas and therefore a hypothalamic EVN may be misdiagnosed as a hypothalamic glioma. Also, the pathologic-radiologic-clinical correlation of EVN located in the hypothalamic area may be different from that of EVNs originating from other usual sites.

The Korean guideline for colorectal cancer screening

Colorectal cancer is the third most common cancer in Korea; it is the second most common cancer in men and the third most common in women. The incidence rate in Korea has continuously increased since 1999 when the National Cancer Registry statistics began. Currently; there are several screening modalities; that have been recommended by expert societies, including fecal occult blood test, colonoscopy, computed tomographic colonography The annual fecal immunochemical test (FIT) has been used in adults aged 50 and older as part of the National Cancer Screening Program in Korea since 2004. Although several study results from regional or national colorectal cancer screening programs in other countries have been reported, the National Cancer Screening Program in Korea has not yet been evaluated with evidence-based methods. Herein report the consensus statements on the National Screening Guideline for colorectal cancer developed by a multi-society expert committee in Korea, as follows: 1) We recommend annual or biennial FIT for screening for colorectal cancer in asymptomatic adults, beginning at 45 years of age and continuing until 80 years (recommendation B). 2) There is no evidence for the risks or benefits of FIT in adults older than 80 years (recommendation I). 3) Selective use of colonoscopy for colorectal cancer screening is recommended, taking into consideration individual preference and the risk of colorectal cancer (recommendation C). 4) There is no evidence for the risks or benefits of double-contrast barium enema for colorectal cancer screening in asymptomatic adults (recommendation I). 5) There is no evidence for the risks or benefits of computed tomographic colonography for colorectal cancer screening in asymptomatic adults (recommendation I).

Cholangiolocellular carcinoma with satellite nodules showing intermediate differentiation

No abstract available.

Tumor Sprouting in Papillary Thyroid Carcinoma Is Correlated with Lymph Node Metastasis and Recurrence

BACKGROUND: Identification of poor prognostic factors in papillary thyroid carcinoma (PTC) patients is important for the patients' care and follow-up. We can sometimes see small tumor clusters without desmoplasia and no evidence of lymphatic emboli around the main tumor mass of PTC. We termed this form of tumor clustering, 'tumor sprouting,' and determined whether these tumors correlate with lymphovascular invasion, lymph node metastasis, and recurrence. METHODS: We analyzed a total of 204 cases of papillary thyroid macrocarcinoma. Number, size and distance from the main tumor of the tumor sprouting were observed and analyzed with clinicopathologic characteristics. RESULTS: Tumor sprouting was observed in 101 patients. Presence of tumor sprouting was significantly associated with positive resection margin (p=.002), lymphovascular invasion (p=.001), lymph node metastasis (p<.001), and recurrence (p=.004). Univariate analysis of recurrence-free survival revealed that tumor multiplicity (p=.037), positive resection margin (p=.007), lymphovascular invasion (p=.004), lymph node metastasis (p<.001), and tumor sprouting (p=.004) were poor prognostic factors. In multivariate analysis, positive resection margin was an independent poor prognostic factor of recurrence. CONCLUSIONS: In conclusion, tumor sprouting is significantly correlated with lymph node metastasis and recurrence. Evaluation of tumor sprouting in PTC patients could be helpful in predicting tumor recurrence or lymph node metastasis.

A Case of Pancreatic Neuroendocrine Tumor Mimicked Intraductal Papillary Mucinous Neoplasm / 대한췌담도학회지

Neuroendocrine tumors of the pancreas are exremely rare tumors, but recent imaging examination advances, diagnostic frequency is also increasing. However, there is difficulty of diagnosis of pancreatic serotonin producing neuroendocrine tumors, because tumors grow slowly and clinical symptoms are not significant. A 60-year-old male patient with pancreatic duct dilatation progresses gradually during the seven years without obstructing lesion in imaging studies, we suspected the mass as intraductal papillary mucinous neoplasm. However, we diagnosed his case as neuroendocrine tumor after surgery and report here with literature review.