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1.
Article in English | WPRIM | ID: wpr-918226

ABSTRACT

Objective@#To validate the performance of 3T spin-echo echo-planar imaging (SE-EPI) magnetic resonance elastography (MRE) for staging hepatic fibrosis in a large population, using surgical specimens as the reference standard. @*Materials and Methods@#This retrospective study initially included 310 adults (155 undergoing hepatic resection and 155 undergoing donor hepatectomy) with histopathologic results from surgical liver specimens. They underwent 3T SE-EPI MRE ≤ 3 months prior to surgery. Demographic findings, underlying liver disease, and hepatic fibrosis pathologic stage according to METAVIR were recorded. Liver stiffness (LS) was measured by two radiologists, and inter-reader reproducibility was evaluated using the intraclass correlation coefficient (ICC). The mean LS of each fibrosis stage (F0–F4) was calculated in total and for each etiologic subgroup. Comparisons among subgroups were performed using the Kruskal–Wallis test and Conover post-hoc test. The cutoff values for fibrosis staging were estimated using receiver operating characteristic (ROC) curve analysis. @*Results@#Inter-reader reproducibility was excellent (ICC, 0.98; 95% confidence interval, 0.97–0.99). The mean LS values were 1.91, 2.41, 3.24, and 5.41 kPa in F0–F1 (n = 171), F2 (n = 26), F3 (n = 38), and F4 (n = 72), respectively. The discriminating cutoff values for diagnosing ≥ F2, ≥ F3, and F4 were 2.18, 2.71, and 3.15 kPa, respectively, with the ROC curve areas of 0.97–0.98 (sensitivity 91.2%–95.9%, specificity 90.7%–99.0%). The mean LS was significantly higher in patients with cirrhosis (F4) of nonviral causes, such as primary biliary cirrhosis (9.56 kPa) and alcoholic liver disease (7.17 kPa) than in those with hepatitis B or C cirrhosis (4.28 and 4.92 kPa, respectively). There were no statistically significant differences in LS among the different etiologic subgroups in the F0–F3 stages. @*Conclusion@#The 3T SE-EPI MRE demonstrated high interobserver reproducibility, and our criteria for staging hepatic fibrosis showed high diagnostic performance. LS was significantly higher in patients with non-viral cirrhosis than in those with viral cirrhosis.

2.
Gut and Liver ; : 129-137, 2022.
Article in English | WPRIM | ID: wpr-914385

ABSTRACT

Background/Aims@#Neoadjuvant chemotherapy is increasingly utilized in patients with borderline or locally advanced pancreatic cancer (LAPC). However, the pathologic evaluation of tumor regression is not routinely performed or well established. We aimed to evaluate the prognostic value of three tumor regression grading systems frequently used in LAPC and to determine the correlation between pathologic and clinical response. @*Methods@#We included a total of 38 patients with LAPC who were treated with neoadjuvant chemotherapy and subsequent resection. Pathologic tumor regression was graded based on the College of American Pathologists (CAP), Evans, and MD Anderson grading systems. @*Results@#One out of 38 patients (2.6%) achieved a pathologic complete response. Unlike other grading systems (Evans, p=0.063; MD Anderson, p=0.110), the CAP grading system was a significant prognostic factor for overall survival (p=0.043). Pathologic N stage (p=0.023), margin status (p=0.044), and radiologic response (p=0.016) correlated with overall survival. In the multivariate analysis, CAP 3 was an independent predictor of shorter overall survival (p=0.026). The CAP grading system correlated with the radiologic response (p=0.007) but not the carbohydrate antigen 19-9 level (p=0.333). @*Conclusions@#The four-tier CAP pathologic tumor regression grading system predicted the clinical outcome in LAPC patients who underwent resection after neoadjuvant chemotherapy. Therefore, a more comprehensive pathologic evaluation is warranted in these patients.

3.
Article in English | WPRIM | ID: wpr-913536

ABSTRACT

Purpose@#The clinical significance of margin status in pancreatic head cancer is still controversial due to the nonstandardized definition of R status and pathologic reporting. This study aims to evaluate the impact of the margin status including location and the role of radiation therapy in pancreatic head cancer. @*Methods@#A total of 314 patients who underwent curative-intent surgery for pancreatic head cancer between 2010 and 2017 were analyzed. Demographics, survival, and local recurrences were compared according to 2 definitions: 0-mm R1 as direct involvement and 1-mm R1 as close resection margin less than 1 mm. The specific margins were divided into 4 groups according to the location around the pancreas: pancreas transection, anterior surface, posterior surface, and vessel (superior mesenteric artery/superior mesenteric vein) margin. @*Results@#The 0-mm R1-rate was 15.6%, and increased to 36.3% in 1-mm R1. The median overall survival rate of 0-mm R0 vs. R1 was 26 months vs. 16 months (P = 0.052) and that of 1-mm R0 vs. R1 was 27 months vs. 18 months, respectively (P = 0.016). In individual margins, posterior, anterior surface, and pancreas transection margin involvement were associated with poor outcome, and the 1 mm posterior surface involvement was an independent risk factor for disease-free survival (hazard ratio, 1.63). Adjuvant radiation therapy had oncologic benefits, especially in R1 patients (P = 0.011) compared to R0 patients (P = 0.088). @*Conclusion@#Margin status, especially 1-mm R1 status is an important predictive factor, and involved posterior surface has a clinical impact. Patients with positive margins should be considered adjuvant radiation therapy.

4.
Article in English | WPRIM | ID: wpr-926982

ABSTRACT

A biliary anastomotic stricture developed 13 months after living donor liver transplantation in a 19-year-old male with congenital hepatic fibrosis. Endoscopic management with balloon dilation followed by the placement of a 7F plastic stent was performed for the anastomotic stricture. After 6 months of indwelling of the stent, the plastic stent was removed because the stenosis and cholestasis were improved. One month after stent removal, he was admitted for acute liver graft failure owing to cholestatic hepatitis, and required retransplantation secondary to graft loss.

5.
Article in English | WPRIM | ID: wpr-926769

ABSTRACT

Objective@#CT plays a central role in determining the resectability of pancreatic cancer, which directs the use of neoadjuvant therapy. This study aimed to assess the diagnostic accuracy of CT in predicting circumferential resection margin (CRM) involvement in patients with resectable or borderline resectable pancreatic head cancer. @*Materials and Methods@#Seventy-seven patients who were scheduled for upfront surgery for resectable or borderline resectable pancreatic head cancer were prospectively enrolled, and 75 patients (38 male and 37 female; mean age ± standard deviation, 68 ± 11 years) were finally analyzed. The CRM status was evaluated separately for the superior mesenteric artery (SMA) and posterior and superior mesenteric vein/portal vein (SMV/PV) margins. Three independent radiologists reviewed the preoperative CT images and evaluated the resection margin status. The reference standard for CRM status was pathologic examination of pancreaticoduodenectomy specimens in an axial plane perpendicular to the axis of the second portion of the duodenum. The diagnostic accuracy of CT was assessed for overall CRM involvement, defined as involvement of the SMA or posterior margins (per-patient analysis), and involvement of each of the three resection margins (per-margin analysis). The data were pooled using a crossed random effects model. @*Results@#Forty patients had pathologically confirmed overall CRM involvement in pancreatic cancer, while CRM involvement was not seen in 35 patients. For overall CRM involvement, the pooled sensitivity and specificity were 15% (95% confidence interval: 7%–49%) and 99% (96%–100%), respectively. For each of the resection margins, the pooled sensitivity and specificity were 14% (9%–54%) and 99% (38%–100%) for the SMA margin, 12% (8%–46%) and 99% (97%–100%) for the posterior margin; and 37% (29%–53%) and 96% (31%–100%) for the SMV/PV margin, respectively. @*Conclusion@#CT showed very high specificity but low sensitivity in predicting pathological CRM involvement in pancreatic cancer.

6.
Gut and Liver ; : 613-624, 2022.
Article in English | WPRIM | ID: wpr-937611

ABSTRACT

Background/Aims@#Intrahepatic cholangiocarcinoma (iCCA) with a ductal plate malformation (DPM) pattern is a recently recognized rare variant. The genomic profile of iCCA with DPM pattern needs to be elucidated. @*Methods@#Cases of iCCA with DPM pattern were retrospectively reviewed based on the medical records, pathology slides, and magnetic resonance imaging (MRI) reports collected between 2010 to 2019 at a single center. Massive parallel sequencing was performed for >500 cancerrelated genes. @*Results@#From a total of 175 iCCAs, five (2.9%) cases of iCCA with DPM pattern were identified. All cases were of the small duct type, and background liver revealed chronic B viral or alcoholic hepatitis. Three iCCAs with DPM pattern harbored MRI features favoring the diagnosis of hepatocellular carcinoma, whereas nonspecific imaging features were observed in two cases. All patients were alive without recurrence during an average follow-up period of 57 months. Sequencing data revealed 64 mutated genes in the five cases, among which FGFR2 and PTPRT were most frequently mutated (three cases each) including an FGFR2-TNC fusion in one case. Mutations in ARID1A and CDKN2A were found in two cases, and mutations in TP53, BAP1, ATM, NF1, and STK11 were observed in one case each. No IDH1, KRAS, or PBRM1 mutations were found. @*Conclusions@#iCCAs with DPM pattern have different clinico-radio-pathologic and genetic characteristics compared to conventional iCCAs. Moreover, FGFR2 and FGFR2 variants were identified. Altogether, these findings further suggest that iCCA with DPM pattern represents a specific subtype of small duct type iCCA.

7.
Gut and Liver ; : 625-636, 2022.
Article in English | WPRIM | ID: wpr-937609

ABSTRACT

Background/Aims@#Three-dimensional cultures of human pancreatic cancer tissue also known as “organoids” have largely been developed from surgical specimens. Given that most patients present with locally advanced and/or metastatic disease, such organoids are not representative of the majority of patients. Therefore, we used endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) to collect pancreatic cancer tissues from patients with advanced pancreatic cancer to create organoids, and evaluated their utility in pancreatic cancer research. @*Methods@#Single-pass EUS-FNA samplings were employed to obtain the tissue for organoid generation. After establishment of the organoid, we compared the core biopsy tissues with organoids using hematoxylin and eosin staining, and performed whole exome sequencing (WES) to detect mutational variants. Furthermore, we compared patient outcome with the organoid drug response to determine the potential utility of the clinical application of such organoid-based assays. @*Results@#Organoids were successfully generated in 14 of 20 tumors (70%) and were able to be passaged greater than 5 times in 12 of 20 tumors (60%). Among them, we selected eight pairs of organoid and core biopsy tissues for detailed analyses. They showed similar patterns in hematoxylin and eosin staining. WES revealed mutations in KRAS, TP53, CDKN2A, SMAD4, BRCA1, and BRCA2 which were 93% homologous, and the mean nonreference discordance rate was 5.47%. We observed moderate drug response correlations between the organoids and clinical outcomes in patients who underwent FOLFIRINOX chemotherapy. @*Conclusions@#The established organoids from EUS-FNA core biopsies can be used for a suitable model system for pancreatic cancer research

8.
Article in English | WPRIM | ID: wpr-900500

ABSTRACT

Background@#Preoperative locoregional treatment (LRT) for hepatocellular carcinoma (HCC) often induces intratumoral necrosis without affecting the overall tumor size, and residual viable tumor size (VTS) on imaging is an important clinical parameter for assessing post-treatment response. However, for surgical specimens, it is unclear whether the VTS would be more relevant to prognosis compared to total tumor size (TTS). @*Methods@#A total of 142 surgically resected solitary HCC cases were retrospectively reviewed. The TTS and VTS were assessed by applying the modified Response Evaluation Criteria in Solid Tumors method to the resected specimens, and correlated with the clinicopathological features and survival. @*Results@#As applying VTS, 13/142 cases (9.2%) were down-staged to ypT1a. Although the survival analysis results for overall survival according to TTS or VTS were similar, VTS was superior to predict disease-free survival (DFS; p = .023) compared to TTS (p = .08). In addition, multivariate analysis demonstrated VTS > 2 cm to be an independent predictive factor for decreased DFS (p = .001). In the subpopulation of patients with LRT (n = 54), DFS in HCCs with TTS or VTS > 2 cm were significantly shorter than those with TTS or VTS ≤ 2 cm (p = .047 and p = .001, respectively). Interestingly, HCCs with TTS > 2 cm but down-staged to VTS ≤ 2 cm after preoperative LRT had similar survival to those with TTS ≤ 2 cm. @*Conclusions@#Although the prognostic impact of tumor size was similar regardless of whether TTS or VTS was applied, reporting VTS may help to increase the number of candidates for surgery in HCC patients with preoperative LRT.

9.
Article in English | WPRIM | ID: wpr-900495

ABSTRACT

Hepatocellular adenoma (HCA) is a heterogeneous entity, from both the histomorphological and molecular aspects, and the resultant subclassification has brought a strong translational impact for both pathologists and clinicians. In this review, we provide an overview of the recent updates on HCA from the pathologists’ perspective and discuss several practical issues and pitfalls that may be useful for diagnostic practice.

10.
Gut and Liver ; : 466-475, 2021.
Article in English | WPRIM | ID: wpr-898456

ABSTRACT

Background/Aims@#Although many studies have reported the promising effect of neoadjuvant treatment for borderline resectable pancreatic cancer (BRPC) to increase resectability, only a few studies have recommended the use of first-line chemotherapeutic agents as neoadjuvant treatment for BRPC. The current study compared clinical outcomes between gemcitabine and FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) in patients with BRPC. @*Methods@#In this single-center retrospective study, 100 BRPC patients treated with neoadjuvant chemotherapy and resection from 2008 to 2018 were reviewed. Clinical outcomes included overall survival, resectability, and recurrence patterns after gemcitabine or FOLFIRINOX treatment. @*Results@#For neoadjuvant chemotherapy, gemcitabine was administered to 34 patients and FOLFIRINOX to 66. Neoadjuvant radiotherapy was administered to 27 patients (79.4%) treated with gemcitabine and 19 (28.8%) treated with FOLFIRINOX (p<0.001). The 2- and 5-year survival rates (YSRs) were significantly higher after FOLFIRINOX (2YSR, 72.2%; 5YSR, 46.0%) than after gemcitabine (2YSR, 58.4%; 5YSR, 19.1%; p=0.041). The margin negative rate was comparable (gemcitabine, 94.1%; FOLFIRINOX, 92.4%; p=0.753), and the tumor size change in percentage showed only a marginal difference (gemcitabine, 20.5%; FOLFIRINOX, 29.0%; p=0.069). Notably, the metastatic recurrence rate was significantly lower in the FOLFIRINOX group (n=20, 52.6%) than in the gemcitabine group (n=22, 78.6%; p=0.001). The rate of adverse events after chemotherapy was significantly higher with FOLFIRINOX than with gemcitabine (43.9%, 20.6%, respectively; p=0.037). @*Conclusions@#FOLFIRINOX provided more clinical and oncological benefit than gemcitabine, with significantly higher overall survival and lower cumulative recurrence rates in BRPC. However, since FOLFIRINOX causes more adverse effects, the regimen should be individualized based on patient’s general condition and clinical status.

11.
Endocrinology and Metabolism ; : 1243-1253, 2021.
Article in English | WPRIM | ID: wpr-914234

ABSTRACT

Background@#Farnesoid X receptor (FXR), a bile acid–activated nuclear receptor, is a potent regulator of glucose and lipid metabolism as well as of bile acid metabolism. Previous studies have demonstrated that FXR deficiency is associated with metabolic derangements, including atherosclerosis and nonalcoholic fatty liver disease (NAFLD), but its mechanism remains unclear. In this study, we investigated the role of FXR in atherosclerosis and NAFLD and the effect of peroxisome proliferator-activated receptor (PPAR) agonists in mouse models with FXR deficiency. @*Methods@#En face lipid accumulation analysis, liver histology, serum levels of glucose and lipids, and mRNA expression of genes related to lipid metabolism were compared between apolipoprotein E (ApoE)−/− and ApoE−/−FXR−/− mice. The effects of PPARα and PPARγ agonists were also compared in both groups of mice. @*Results@#Compared with ApoE−/− mice, ApoE−/−FXR−/− mice showed more severe atherosclerosis, hepatic steatosis, and higher levels of serum cholesterol, low-density lipoprotein cholesterol, and triglycerides, accompanied by increased mRNA expression of FAS, ApoC2, TNFα, IL-6 (liver), ATGL, TGH, HSL, and MGL (adipocytes), and decreased mRNA expressions of CPT2 (liver) and Tfam (skeletal muscle). Treatment with a PPARα agonist, but not with a PPARγ agonist, partly reversed atherosclerosis and hepatic steatosis, and decreased plasma triglyceride levels in the ApoE−/−FXR−/− mice, in association with increased mRNA expression of CD36 and FATP and decreased expression of ApoC2 and ApoC3 (liver). @*Conclusion@#Loss of FXR is associated with aggravation of atherosclerosis and hepatic steatosis in ApoE-deficient mice, which could be reversed by a PPARα agonist through induction of fatty acid uptake, β-oxidation, and triglyceride hydrolysis.

12.
Gut and Liver ; : 466-475, 2021.
Article in English | WPRIM | ID: wpr-890752

ABSTRACT

Background/Aims@#Although many studies have reported the promising effect of neoadjuvant treatment for borderline resectable pancreatic cancer (BRPC) to increase resectability, only a few studies have recommended the use of first-line chemotherapeutic agents as neoadjuvant treatment for BRPC. The current study compared clinical outcomes between gemcitabine and FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) in patients with BRPC. @*Methods@#In this single-center retrospective study, 100 BRPC patients treated with neoadjuvant chemotherapy and resection from 2008 to 2018 were reviewed. Clinical outcomes included overall survival, resectability, and recurrence patterns after gemcitabine or FOLFIRINOX treatment. @*Results@#For neoadjuvant chemotherapy, gemcitabine was administered to 34 patients and FOLFIRINOX to 66. Neoadjuvant radiotherapy was administered to 27 patients (79.4%) treated with gemcitabine and 19 (28.8%) treated with FOLFIRINOX (p<0.001). The 2- and 5-year survival rates (YSRs) were significantly higher after FOLFIRINOX (2YSR, 72.2%; 5YSR, 46.0%) than after gemcitabine (2YSR, 58.4%; 5YSR, 19.1%; p=0.041). The margin negative rate was comparable (gemcitabine, 94.1%; FOLFIRINOX, 92.4%; p=0.753), and the tumor size change in percentage showed only a marginal difference (gemcitabine, 20.5%; FOLFIRINOX, 29.0%; p=0.069). Notably, the metastatic recurrence rate was significantly lower in the FOLFIRINOX group (n=20, 52.6%) than in the gemcitabine group (n=22, 78.6%; p=0.001). The rate of adverse events after chemotherapy was significantly higher with FOLFIRINOX than with gemcitabine (43.9%, 20.6%, respectively; p=0.037). @*Conclusions@#FOLFIRINOX provided more clinical and oncological benefit than gemcitabine, with significantly higher overall survival and lower cumulative recurrence rates in BRPC. However, since FOLFIRINOX causes more adverse effects, the regimen should be individualized based on patient’s general condition and clinical status.

13.
Article in English | WPRIM | ID: wpr-892796

ABSTRACT

Background@#Preoperative locoregional treatment (LRT) for hepatocellular carcinoma (HCC) often induces intratumoral necrosis without affecting the overall tumor size, and residual viable tumor size (VTS) on imaging is an important clinical parameter for assessing post-treatment response. However, for surgical specimens, it is unclear whether the VTS would be more relevant to prognosis compared to total tumor size (TTS). @*Methods@#A total of 142 surgically resected solitary HCC cases were retrospectively reviewed. The TTS and VTS were assessed by applying the modified Response Evaluation Criteria in Solid Tumors method to the resected specimens, and correlated with the clinicopathological features and survival. @*Results@#As applying VTS, 13/142 cases (9.2%) were down-staged to ypT1a. Although the survival analysis results for overall survival according to TTS or VTS were similar, VTS was superior to predict disease-free survival (DFS; p = .023) compared to TTS (p = .08). In addition, multivariate analysis demonstrated VTS > 2 cm to be an independent predictive factor for decreased DFS (p = .001). In the subpopulation of patients with LRT (n = 54), DFS in HCCs with TTS or VTS > 2 cm were significantly shorter than those with TTS or VTS ≤ 2 cm (p = .047 and p = .001, respectively). Interestingly, HCCs with TTS > 2 cm but down-staged to VTS ≤ 2 cm after preoperative LRT had similar survival to those with TTS ≤ 2 cm. @*Conclusions@#Although the prognostic impact of tumor size was similar regardless of whether TTS or VTS was applied, reporting VTS may help to increase the number of candidates for surgery in HCC patients with preoperative LRT.

14.
Article in English | WPRIM | ID: wpr-892791

ABSTRACT

Hepatocellular adenoma (HCA) is a heterogeneous entity, from both the histomorphological and molecular aspects, and the resultant subclassification has brought a strong translational impact for both pathologists and clinicians. In this review, we provide an overview of the recent updates on HCA from the pathologists’ perspective and discuss several practical issues and pitfalls that may be useful for diagnostic practice.

15.
Journal of Liver Cancer ; : 17-24, 2020.
Article | WPRIM | ID: wpr-836096

ABSTRACT

Hepatocellular carcinoma (HCC) is heterogeneous in pathogenesis, phenotype and biological behavior. Various histopathological features of HCC had been sporadically described, and with the identification of common molecular alterations of HCC and its genomic landscape over the last decade, morpho-molecular correlation of HCC has become possible. As a result, up to 35% of HCCs can now be classified into histopathological variants, many of which have unique molecular characteristics. This review will provide an introduction to the variously described histopathological variants of HCC in the updated WHO Classification of Digestive System Tumors.

16.
Article | WPRIM | ID: wpr-834567

ABSTRACT

Pathologic interpretation of endoscopic ultrasound–guided fine needle aspiration (EUS-FNA) cytology/biopsy specimens is one of the most challenging tasks in cytology and surgical pathology practice, as the procedure often yields minimal amounts of diagnostic material and contains contaminants, such as blood cells and normal intestinal mucosa. EUS-FNA cytology/biopsy will nevertheless become a more popular procedure for evaluation of various pancreatic lesions because they are difficult to approach with conventional endoscopic procedures. Pathologists should understand the structural differences and limitations of EUS-FNA that make pathologic diagnosis difficult. Ancillary tests are available for differential diagnosis of EUS-FNA for various pancreatic lesions. Immunostains are the most commonly used ancillary tests, and pathologists should able to choose the necessary panel for differential diagnosis. Pathologists should review clinical history and radiologic and/or EUS findings before selecting an immunostain panel and making a pathologic diagnosis. In addition, one’s threshold of malignancy should be adjusted according to the appropriate clinical setting to avoid under-evaluation of pathologic diagnoses. Clinico-pathologic correlation is essential in pathologic evaluation of EUS-FNA for pancreatic lesions. Pathologists can reduce errors by correlating clinical and radiologic findings when evaluating EUS-FNA. Some molecular tests can be applied in differential diagnosis of pancreatic neoplastic and cystic lesions. Molecular data should be used as supportive evidence of a specific disease entity, rather than direct evidence, and should be correlated with clinico-pathologic findings to avoid errors in pathologic diagnosis.

17.
Korean Journal of Radiology ; : 1115-1125, 2020.
Article | WPRIM | ID: wpr-833576

ABSTRACT

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a primary liver cancer (PLC) with both hepatocytic and cholangiocytic phenotypes. Recently, the World Health Organization (WHO) updated its histological classification system for cHCC-CCA.Compared to the previous WHO histological classification system, the new version no longer recognizes subtypes of cHCC-CCA with stem cell features. Furthermore, some of these cHCC-CCA subtypes with stem cell features have been recategorized as either hepatocellular carcinomas (HCCs) or intrahepatic cholangiocarcinomas (ICCs). Additionally, distinctive diagnostic terms for intermediate cell carcinomas and cholangiolocarcinomas (previous cholangiolocellular carcinoma subtype) are now recommended. It is important for radiologists to understand these changes because of its potential impact on the imagingbased diagnosis of HCC, particularly because cHCC-CCAs frequently manifest as HCC mimickers, ICC mimickers, or as indeterminate on imaging studies. Therefore, in this review, we introduce the 2019 WHO classification system for cHCC-CCA, illustrate important imaging features characteristic of its subtypes, discuss the impact on imaging-based diagnosis of HCC, and address other important considerations.

18.
Gut and Liver ; : 521-528, 2020.
Article | WPRIM | ID: wpr-833121

ABSTRACT

Background/Aims@#Desmoplasia is a prominent feature of pancreatic ductal adenocarcinoma (PDA). Stromal desmoplasia reflects the low cellularity that is characteristic of PDA, and it may play a role in PDA chemoresistance. In this retrospective study, we evaluated the relationship between tumor cellularity in resected PDA specimens and long-term patient outcomes. @*Methods@#We retrospectively reviewed the data from 175 patients who underwent PDA resection between January 2010 and December 2015 at Seoul National University Bundang Hospital, and analyzed their clinicopathological features and the relationship between tumor cellularity (high vs low based on a cutoff of 30% cellularity) and patient outcomes. @*Results@#The high-cellularity group had significantly shorter overall survival (OS) (18.7 months vs 26.6 months, p=0.006) and disease-free survival (11.0 months vs 16.9 months, p=0.031) than the low-cellularity group. Multivariate analysis revealed that high tumor cellularity was an independent risk factor for poor OS (hazard ratio, 2.008; 95% confidence interval, 1.361 to 2.962; p<0.001). Adjuvant therapy improved OS in the low-cellularity group (16.3 months vs 41.3 months, p=0.001) but not in the high-cellularity group (15.9 months vs 24.4 months, p=0.107). @*Conclusions@#Tumor cellularity in PDA specimens may be a prognostic and predictive biomarker that could aid in identifying patients who would benefit from adjuvant therapy for PDA.

19.
Article | WPRIM | ID: wpr-831071

ABSTRACT

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.

20.
Korean Journal of Radiology ; : 1322-1330, 2020.
Article in English | WPRIM | ID: wpr-902395

ABSTRACT

Objective@#The aim of this study was to prospectively evaluate whether liver stiffness (LS) assessments, obtained by twodimensional (2D)-shear wave elastography (SWE) with a propagation map, can evaluate liver fibrosis stage using histopathology as the reference standard. @*Materials and Methods@#We prospectively enrolled 123 patients who had undergone percutaneous liver biopsy from two tertiary referral hospitals. All patients underwent 2D-SWE examination prior to biopsy, and LS values (kilopascal [kPa]) were obtained. On histopathologic examination, fibrosis stage (F0–F4) and necroinflammatory activity grade (A0–A4) were assessed. Multivariate linear regression analysis was performed to determine the significant factors affecting the LS value.The diagnostic performance of the LS value for staging fibrosis was assessed using receiver operating characteristic (ROC) analysis, and the optimal cut-off value was determined by the Youden index. @*Results@#Reliable measurements of LS values were obtained in 114 patients (92.7%, 114/123). LS values obtained from 2D-SWE with the propagation map positively correlated with the progression of liver fibrosis reported from histopathology (p < 0.001). According to the multivariate linear regression analysis, fibrosis stage was the only factor significantly associated with LS (p < 0.001). The area under the ROC curve of LS from 2D-SWE with the propagation map was 0.773, 0.865, 0.946, and 0.950 for detecting F ≥ 1, F ≥ 2, F ≥ 3, and F = 4, respectively. The optimal cut-off LS values were 5.4, 7.8, 9.4, and 12.2 kPa for F ≥ 1, F ≥ 2, F ≥ 3, and F = 4, respectively. The corresponding sensitivity and specificity of the LS value for detecting cirrhosis were 90.9% and 88.4%, respectively. @*Conclusion@#The LS value obtained from 2D-SWE with a propagation map provides excellent diagnostic performance in evaluating liver fibrosis stage, determined by histopathology.

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