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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.
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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.
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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.
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PURPOSE: While the incidence of Barrett's neoplasia has been increasing in Western countries, the disease remains rare in Asian countries. Therefore, very few studies have investigated the endoscopic treatment for Barrett's neoplasia in Korea. Endoscopic submucosal dissection (ESD) enables en bloc and complete resection of gastrointestinal neoplastic lesions. This study aimed to evaluate the therapeutic outcomes of ESD for Barrett's neoplasia in a single center in Korea and to examine the predictive factors for incomplete resection. MATERIALS AND METHODS: We conducted a retrospective observational study of 18 patients who underwent ESD for superficial Barrett's neoplasia (dysplasia and early cancer) between January 2010 and December 2019 at Pusan National University Hospital. The therapeutic outcomes of ESD and procedure-related complications were analyzed. RESULTS: En bloc resection, complete resection, and curative resection were performed in 94%, 72%, and 61% of patients, respectively. Histopathology (submucosal or deeper invasion of the tumor) was a significant predictive factor for incomplete resection (P=0.047). Procedure-related bleeding and stenosis were not observed, whereas perforation occurred in one case. During the median follow-up period of 12 months (range, 6-74 months), local recurrence occurred in 2 patients with incomplete resection, one patient underwent repeat ESD, and the other patient received concurrent chemoradiotherapy. The 3-year overall and disease-specific survival rates were 73% and 93%, respectively. CONCLUSIONS: ESD seems to be an effective and safe treatment for superficial Barrett's neoplasia in Korea. Nevertheless, the suitability of ESD for Barrett's cancer cases should be determined considering the high risk of deep submucosal invasion.
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Background/Aims: Papillary gastric cancer (GC) is classified as differentiated adenocarcinoma, together with well-differentiated (WD) and moderately differentiated (MD) adenocarcinoma. This study evaluated the risk of lymph node metastasis (LNM) in submucosal (SM) invasive papillary GC compared with other differentiated early GC types. Methods: This retrospective study involved three tertiary hospitals and enrolled 1,798 lesions with differentiated SM invasive GC treated with curative gastrectomy between March 2001 and December 2012. All pathology slides were reviewed, and clinicopathologic findings associated with LNM, including tumor size, location, gross type, ulceration, depth and width of SM invasion, and lymphovascular invasion (LVI), were analyzed. Results: The proportion of SM papillary GC was 2.8% (n=51). SM papillary GC was associated with larger tumor size and deeper and wider SM invasion than other differentiated GC types. LNM was significantly higher in the papillary type than in the MD and WD types. LNM was found in 27.5% of SM papillary GC patients (WD: 9.0%, MD: 21.2%). LVI was the only significant risk factor for LNM in SM papillary GC. The depth or width of SM invasion was not associated with LNM in papillary GC. Lower third location or elevated gross appearance was significantly associated with LVI. Conclusions: SM papillary GC had the highest LNM rate, with features different from those of other differentiated SM invasive GCs. The treatment strategy for SM papillary GC should be carefully approached, especially for lesions located in the lower third or of the elevated gross type.
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Neoplasias Gástricas , Gastrectomia , Mucosa Gástrica , Humanos , Excisão de Linfonodo , Invasividade Neoplásica , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/cirurgiaRESUMO
Background/Aims: Achalasia is an esophageal motor disorder that leads to functional esophageal obstruction. Food stasis and bacterial fermentation can predispose an individual to esophageal mucosal inflammation, causing multifocal dysplasia and increasing the risk of developing esophageal squamous cell carcinoma. We aimed to evaluate esophageal mucosal alterations in achalasia patients and determine clinical factors associated with the histopathological findings. Methods: From 2009 to 2013, we obtained endoscopic biopsies from the lower and middle esophagus of 22 patients with achalasia and 17 controls. Patients' clinical data and histological severity of esophagitis were retrospectively analyzed. Additionally, immunohistochemical staining for CD3, CD20, Ki-67, and p53 was conducted. Results: The median age of achalasia patients was 49.5 years (range, 27 to 82 years), and there were nine males (40.9%). The median symptom duration was 5.8 years (range, 1 to 33.5 years), and 10 patients (45%) underwent previous treatment (nine, balloon dilation; one, botulinum toxin injection). Achalasia patients had significantly more severe esophagitis than did controls (p=0.001, lower esophagus; p=0.008, middle esophagus), and the number of CD3-positive lymphocytes exceeded that of CD20-positive lymphocytes (p<0.001). Achalasia patients also had a higher esophageal Ki-67 proliferation index (p=0.048). Although statistically nonsignificant, p53 expression was only observed in achalasia patients. There was no association between the histological severity of esophagitis and other clinicopathological findings. Conclusions: Achalasia patients showed significantly severe histological esophagitis and a high Ki-67 proliferation index, indicating an increased risk of neoplastic progression. Therefore, careful endoscopic inspection is necessary for the early detection of superficial neoplasia in these patients.
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Acalasia Esofágica , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Adulto , Idoso , Idoso de 80 Anos ou mais , Mucosa Esofágica , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND AND AIMS: Endoscopic resection (ER) for submucosal invasive colorectal cancer (T1 CRC) can be grouped as curative ER (C-ER) and non-curative ER (NC-ER). Little is known about the long-term outcomes of patients in these two groups. Therefore, we have evaluated the long-term outcomes in endoscopically resected T1 CRC patients in C-ER and NC-ER groups. METHODS: We conducted a retrospective study on 220 patients with T1 CRC treated with ER from January 2007 to December 2017. First, we investigated the long-term outcomes (5-year overall survival [OS] and recurrence-free survival [RFS]) in the C-ER group (n = 49). In the NC-ER group (n = 171), we compared long-term outcomes between patients who underwent additional surgical resection (ASR) (n = 117) and those who did not (surveillance-only, n = 54). RESULTS: T1 CRC patients in the C-ER and NC-ER groups had a median follow-up of 44 (interquartile range 32-69) months. There was no risk of tumor recurrence and cancer-related deaths in patients with C-ER. In the NC-ER group, the 5-year OS rates were 75.3% and 92.6% in the surveillance-only and ASR subgroups, respectively. The hazard ratio (HR) for ASR in NC-ER vs. surveillance-only in NC-ER was statistically insignificant. However, RFS rates were significantly different between the ASR (97.2%) and surveillance-only (84.0%) subgroups. Multivariate analysis indicated a submucosal invasion depth (SID) of >2500 µm and margin positivity to be associated with recurrence. CONCLUSIONS: The surveillance-only approach can be considered as an alternative surgical option for T1 CRCs in selected patients undergoing NC-ER.
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Acinar cell carcinomas (ACCs) and mixed acinar-neuroendocrine carcinomas (MAcNECs) of the pancreas are extremely rare carcinomas with a significant component with acinar differentiation. To date, the clinicopathological behaviours of these neoplasms remain unclear. In this study, we evaluated the histopathological and molecular characteristics of 20 ACCs and 13 MAcNECs and compared them to a cohort of 269 well-differentiated pancreatic neuroendocrine tumours (PanNETs). Compared to PanNETs, both ACCs and MAcNECs had an advanced pT classification (p<0.001), as well as more prevalent lymphovascular and perineural invasion (p=0.002) and lymph node and distant metastases (p<0.001). Patients with MAcNECs had worse overall (p<0.001) and recurrence-free survival (p<0.001) than those with PanNETs, but no significant difference with those with ACCs. Subgroup analyses revealed that patients with ACCs and MAcNECs had significantly worse recurrence-free survival than those with grade 1 PanNET (p<0.001), and patients with MAcNECs also had worse overall survival than those with grade 1 and 2 PanNETs (p<0.001, and p=0.001). ACCs presented more commonly with intraductal growth (p=0.014) than MAcNECs, while MAcNECs more often had lymph node metastasis (p=0.012) than ACCs. The telomere maintenance mechanism Alternative Lengthening of Telomeres (ALT) was assessed by telomere-specific FISH, and ALT was detected in 1 of 20 ACCs and in three of the 13 MAcNECs. Patients with MAcNECs and ACCs had worse survival and more aggressive behaviour than those with grade 1 PanNETs; thus, the clinicopathological behaviour of MAcNECs resembles ACCs rather than PanNETs. Combined neuroendocrine and acinar cell immunohistochemical markers are helpful for differentiating these different tumour types.
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Carcinoma de Células Acinares/patologia , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Carcinoma de Células Acinares/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/mortalidade , Neoplasias Pancreáticas/mortalidadeRESUMO
BACKGROUND: IPNB is very rare disease and most previous studies on IPNB were case series with a small number due to low incidence. The aim of this study is to validate previously known clinicopathologic features of intraductal papillary neoplasm of bile duct (IPNB) based on the first largest multicenter cohort. METHODS: Among 587 patients previously diagnosed with IPNB and similar diseases from each center in Korea, 387 were included in this study after central pathologic review. We also reviewed all preoperative image data. RESULTS: Of 387 patients, 176 (45.5%) had invasive carcinoma and 21 (6.0%) lymph node metastasis. The 5-year overall survival was 80.9% for all patients, 88.8% for IPNB with mucosal dysplasia, and 70.5% for IPNB with invasive carcinoma. According to the "Jang & Kim's modified anatomical classification," 265 (68.5%) were intrahepatic, 103 (26.6%) extrahepatic, and 16 (4.1%) diffuse type. Multivariate analysis revealed that tumor invasiveness was a unique predictor for survival analysis. (p = 0.047 [hazard ratio = 2.116, 95% confidence interval 1.010-4.433]). CONCLUSIONS: This is the first Korean multicenter study on IPNB through central pathologic and radiologic review process. Although IPNB showed good long-term prognosis, relatively aggressive features were also found in invasive carcinoma and extrahepatic/diffuse type.
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Neoplasias dos Ductos Biliares , Ductos Biliares Intra-Hepáticos , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares , Estudos de Coortes , Humanos , República da Coreia/epidemiologiaRESUMO
BACKGROUND: Early gastric cancer that meets the expanded criteria for endoscopic resection (ER) is expected to be associated with a negligible risk for lymph node metastasis (LNM); however, recent studies have reported LNM in submucosal gastric cancer patients who met the existing criteria. In this study, we develop the revised criteria for ER of submucosal gastric cancer with the aim of minimizing LNM. METHODS: We analyzed the clinicopathological data of 2461 patients diagnosed with differentiated, submucosal gastric cancer who underwent surgery at three tertiary hospitals between March 2001 and December 2012, and re-analyzed the pathological slides of all patients. The depth of submucosal invasion was measured histopathologically in two different ways (the classic and alternative methods) to obtain accurate data. RESULTS: Of the enrolled subjects, 306 (17.0%) had LNM. The width of submucosal invasion correlated well with the LNM. We defined the depth and width of submucosal infiltration associated with the lowest incidence of LNM. None of the 254 subjects developed LNM when the following criteria were met: tumor diameter ≤ 3 cm, submucosal invasion depth < 1000 µm (as measured using the alternative method), submucosal invasion width < 4 mm, no lymphovascular invasion, and no perineural invasion; however, LNM was observed in 2.7% of subjects (6/218) who met the existing criteria. CONCLUSIONS: We revised the criteria for ER by adopting the alternative method to measure the depth of submucosal invasion and adding the width of such invasion. Our criteria better predicted LNM than the current criteria used to select ER to treat submucosal gastric cancer.
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Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Ressecção Endoscópica de Mucosa , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Vasos Sanguíneos/patologia , Diferenciação Celular , Humanos , Metástase Linfática , Vasos Linfáticos/patologia , Gradação de Tumores , Invasividade Neoplásica , Seleção de Pacientes , Nervos Periféricos/patologia , Estudos Retrospectivos , Carga TumoralRESUMO
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.
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PURPOSE: The most recent 2017 World Health Organization (WHO) classification of pancreatic neuroendocrine neoplasms (PanNENs) has refined the three-tiered 2010 scheme by separating grade 3 pancreatic neuroendocrine tumors (G3 PanNETs) from poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs). However, differentiating between G3 Pan- NETs and PanNECs is difficult in clinical practice. MATERIALS AND METHODS: Eighty-two surgically resected PanNENs were collected from 16 institutions and reclassified according to the 2017 WHO classification based on the histological features and proliferation index (mitosis and Ki-67). Immunohistochemical stains for ATRX, DAXX, retinoblastoma, p53, Smad4, p16, and MUC1 were performed for 15 high-grade PanNENs. RESULTS: Re-classification resulted in 20 G1 PanNETs (24%), 47 G2 PanNETs (57%), eight G3 well-differentiated PanNETs (10%), and seven poorly differentiated PanNECs (9%). PanNECs showed more frequent diffuse nuclear atypia, solid growth patterns and apoptosis, less frequent organoid growth and regular vascular patterns, and absence of low-grade PanNET components than PanNETs. The Ki-67 index was significantly higher in PanNEC (58.2%± 15.1%) compared to G3 PanNET (22.6%±6.1%, p < 0.001). Abnormal expression of any two of p53, p16, MUC1, and Smad4 could discriminate PanNECs from G3 PanNETs with 100% specificity and 87.5% sensitivity. CONCLUSION: Histological features supporting the diagnosis of PanNECs over G3 PanNETs were the absence of a low-grade PanNET component in the tumor, the presence of diffuse marked nuclear atypia, solid growth pattern, frequent apoptosis and markedly increased proliferative activity with homogeneous Ki-67 labeling. Immunohistochemical stains for p53, p16, MUC1, and Smad4 may be helpful in distinguishing PanNECs from G3 PanNETs in histologically ambiguous cases, especially in diagnostic practice when only small biopsied tissues are available.
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Tumores Neuroendócrinos/epidemiologia , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Criança , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Tumores Neuroendócrinos/etiologia , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/terapia , Vigilância da População , Prognóstico , República da Coreia , Sensibilidade e Especificidade , Adulto JovemRESUMO
BACKGROUND: With advances in diagnostic endoscopy, the incidence of superficial colorectal tumors, including laterally spreading tumors (LSTs), has increased. However, little is known about the long-term results of LSTs with positive lateral margin after endoscopic treatment. This study aimed to evaluate the long-term clinical outcomes and risk factors for local recurrence of LSTs with positive lateral margin after initial endoscopic resection. METHODS: We performed a retrospective analysis of the medical records of 324 patients who had 363 LSTs with positive lateral margin after endoscopic resection at a tertiary academic medical center. The medical records from 2011 to 2015 were analyzed. Local recurrence was confirmed through endoscopic finding and subsequent biopsy analysis. We assessed the local recurrence rate and performed multivariate analyses to identify the factors associated with local recurrence. RESULTS: Follow-up colonoscopy was performed in 176 of 363 LSTs. The local recurrence rate was 6.3% (11/176), with a median (interquartile range [IQR]) follow-up period of 19.8 (12.4-46.5) months. In multivariate analysis, local recurrence was associated with piecemeal resection (odds ratio [OR] 6.62, 95% confidence interval [CI] 1.28-34.33; p = 0.024) and inversely associated with thermal ablation (OR 0.033, 95% CI 0.00-0.45; p = 0.011). At surveillance colonoscopy, histology of the recurrent tumor was adenoma in 10 (90.9%) of 11; these were treated endoscopically. CONCLUSIONS: In this retrospective study, we found that endoscopically resected LSTs with positive lateral margin have a low recurrence rate. Piecemeal resection was associated with higher local recurrence, and thermal ablation was inversely associated with local recurrence. Endoscopic resection with positive lateral margin combined with thermal ablation leads to a low recurrence rate.
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Colonoscopia/métodos , Neoplasias Colorretais/cirurgia , Mucosa Intestinal/cirurgia , Biópsia , Neoplasias Colorretais/diagnóstico , Feminino , Seguimentos , Humanos , Mucosa Intestinal/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Rectal neuroendocrine tumors (NETs) < 10 mm in diameter, limited to the submucosa without local or distant metastasis, can be treated endoscopically. Endoscopic mucosal resection with a ligation band device (EMR-L) and endoscopic submucosal dissection (ESD) have been employed to resect rectal NETs. We evaluated and compared the clinical outcomes of EMR-L and ESD for endoscopic resection of rectal NETs G1 < 10 mm in diameter. METHODS: We conducted a retrospective study of 82 rectal NETs in 82 patients who underwent either EMR-L or ESD. Therapeutic outcomes (en bloc resection and complete resection rates), procedure time, and procedure-related adverse events were evaluated. Additionally, we measured the distance of the lateral and vertical margins from the border of the tumor in pathologic specimens and compared the resectability between EMR-L and ESD. RESULTS: Sixty-six lesions were treated using EMR-L and 16 using ESD. En bloc resection was achieved in all patients. The complete resection rate with EMR-L was significantly higher than that with ESD (95.5% vs.75.0%, p = 0.025). The prevalence of vertical margin involvement was significantly higher in the ESD group than in the EMR-L group (12.5% vs. 0%, p = 0.036), and ESD was more time consuming than EMR-L (24.21 ± 12.18 vs. 7.05 ± 4.53 min, p < 0.001). The lateral and vertical margins were more distant in the EMR-L group than in the ESD group (lateral margin distance, 1661 ± 849 vs. 1514 ± 948 µm; vertical margin distance, 277 ± 308 vs. 202 ± 171 µm). CONCLUSIONS: EMR-L is more favorable for small rectal NETs with respect to therapeutic outcomes, procedure time, and technical difficulties. Additionally, EMR-L enables achievement of sufficient vertical margin distances.
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The Cancer Genome Atlas data on gastric carcinoma has identified four biologic pathways as potential drivers of gastric carcinogenesis and suggested targeted therapies based on the genomic alterations underscoring each subset. The correlation between morphology, biologic groups and their corresponding biomarkers has been eluded in several previous studies; however, a comprehensive analysis in consideration of the recent advancements has not been performed. In this study we explored the predictive value of morphology for biomarker expression and its association with protein expression based classification of gastric carcinoma. Four hundred eighty six gastric carcinomas which had been classified into protein expression-based groups formed the case cohort. Upon analysis, we found a low positive predictive value of an individual morphologic pattern for biomarker-expression, indicating that an individual morphologic pattern alone cannot predict PD-L1, Her2/neu expression and EBV- or MSI-gastric cancer. A combination approach targeting the test in certain WHO patterns can be employed for maximizing the positive predictive values. These include, PD-L1 testing in tubular, carcinoma with lymphoid stroma, undifferentiated and poorly cohesive patterns and Her2/neu testing in tubular, mixed, papillary, mucinous and solid patterns. The predictive values and morphologic associations presented here have the potential to select patients for personalized therapy.
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Adenocarcinoma/química , Antígeno B7-H1/análise , Biomarcadores Tumorais/análise , Imuno-Histoquímica , Receptor ErbB-2/análise , Neoplasias Gástricas/química , Adenocarcinoma/classificação , Adenocarcinoma/patologia , Adenocarcinoma/virologia , Antígenos CD/análise , Caderinas/análise , Herpesvirus Humano 4/isolamento & purificação , Humanos , Instabilidade de Microssatélites , Valor Preditivo dos Testes , República da Coreia , Neoplasias Gástricas/classificação , Neoplasias Gástricas/patologia , Neoplasias Gástricas/virologia , Análise Serial de Tecidos , Proteína Supressora de Tumor p53/análise , Estados UnidosRESUMO
Sirtuin 1 (SIRT1) is a histone deacetylase implicated in stem cell homeostasis. Conditional Sirt1 deletion in the hematopoietic stem and progenitor system promotes hematopoietic stem and progenitor cell (HSPC) expansion under stress conditions. In addition, SIRT1 activators modulate the capacity and HSPC numbers in the bone marrow (BM). To investigate the role of SIRT1 in the BM niche, a conditional Sirt1 deletion in the BM niche was generated in a mouse model for the present study. Multicolor flow cytometric analyses were performed to determine HSC cell populations. Using 5-fluorouracil-induced proliferative stress, a survival curve was produced. In the present study, Sirt1 deletion in the BM niche demonstrated that the production of mature blood cells, lineage distribution within hematopoietic organs and frequencies of HSPC populations were comparable to those of controls. Additionally, Sirt1 deletion in the BM niche did not perturb HSC maturation under stress induced by transplantation. Therefore, these observations suggest that SIRT1 serves a dispensable role in HSC maturation in the BM niche.
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OBJECTIVES: Circulating tumor cells (CTCs) in the blood have been used as diagnostic markers in patients with colorectal cancer (CRC). In this study, we evaluated a CTC detection system based on cell size to assess CTCs and their potential as early diagnostic and prognostic biomarkers for CRC. METHODS: From 2014 to 2015, 88 patients with newly diagnosed CRC, who were scheduled for surgery, and 31 healthy volunteers were enrolled and followed up in Pusan National University Hospital. CTCs were enriched using a centrifugal microfluidic system with a new fluid-assisted separation technique (FAST) and detected by cytomorphological evaluation using fluorescence microscopy. RESULTS: Two or more CTCs were detected using FAST in 74 patients and 3 healthy volunteers. The number of CTCs in the CRC group was significantly higher than that in the healthy volunteers (P < 0.001). When a receiver operating characteristic curve was created to differentiate patients with CRC from healthy volunteers, the sensitivity and specificity were almost optimized when the critical CTC value was 5/7.5 mL of blood. When this value was used, the sensitivity and specificity in differentiating patients with CRC from the healthy controls were 75% and 100%, respectively. In patients with CRC with ≥5 CTCs, vascular invasion was frequently identified (P = 0.035). All patients with stage IV were positive for CTCs. Patients with ≥5 CTCs showed a trend toward poor overall and progression-free survival. DISCUSSION: Our study demonstrated promising results with the use of FAST-based CTC detection for the early diagnosis and prognosis of CRC.