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BACKGROUND: Intratumoral heterogeneity (ITH) and tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) play important roles in tumor evolution and patient outcomes. However, the precise characterization of diverse cell populations and their crosstalk associated with PDAC progression and metastasis is still challenging. METHODS: We performed single-cell RNA sequencing (scRNA-seq) of treatment-naïve primary PDAC samples with and without paired liver metastasis samples to understand the interplay between ITH and TME in the PDAC evolution and its clinical associations. RESULTS: scRNA-seq analysis revealed that even a small proportion (22%) of basal-like malignant ductal cells could lead to poor chemotherapy response and patient survival and that epithelial-mesenchymal transition programs were largely subtype-specific. The clonal homogeneity significantly increased with more prevalent and pronounced copy number gains of oncogenes, such as KRAS and ETV1, and losses of tumor suppressor genes, such as SMAD2 and MAP2K4, along PDAC progression and metastasis. Moreover, diverse immune cell populations, including naïve SELLhi regulatory T cells (Tregs) and activated TIGIThi Tregs, contributed to shaping immunosuppressive TMEs of PDAC through cellular interactions with malignant ductal cells in PDAC evolution. Importantly, the proportion of basal-like ductal cells negatively correlated with that of immunoreactive cell populations, such as cytotoxic T cells, but positively correlated with that of immunosuppressive cell populations, such as Tregs. CONCLUSION: We uncover that the proportion of basal-like subtype is a key determinant for chemotherapy response and patient outcome, and that PDAC clonally evolves with subtype-specific dosage changes of cancer-associated genes by forming immunosuppressive microenvironments in its progression and metastasis.
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Evolución Clonal , Neoplasias Hepáticas , Neoplasias Pancreáticas , Microambiente Tumoral , Femenino , Humanos , Masculino , Adenocarcinoma/genética , Adenocarcinoma/patología , Biomarcadores de Tumor/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Evolución Clonal/genética , Transición Epitelial-Mesenquimal/genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Pronóstico , Análisis de Expresión Génica de una Sola Célula , Transcriptoma , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma (PDAC) has the worst survival rate among tumors. At the time of diagnosis, more than 80% of PDACs are considered to be surgically unresectable, and there is an unmet need for treatment options in these inoperable PDACs. This study aimed to establish a patient-derived organoid (PDO) platform from EUS-guided fine-needle biopsy (EUS-FNB) collected at diagnosis and to determine its clinical applicability for the timely treatment of unresectable PDAC. METHODS: Patients with suspected PDAC were prospectively enrolled at the Samsung Medical Center from 2015 to 2019. PDAC tissues were acquired by means of EUS-FNB to establish PDAC PDOs, which were comprehensively analyzed for histology, genomic sequencing, and high-throughput screening (HTS) drug sensitivity test. RESULTS: PDAC PDOs were established with a success rate of 83.2% (94/113). It took approximately 3 weeks from acquiring minimal EUS-FNB specimens to generating sufficient PDAC PDOs for the simultaneous HTS drug sensitivity test and genomic sequencing. The high concordance between PDAC tissues and matched PDOs was confirmed, and whole-exome sequencing revealed the increased detection of genetic alterations in PDOs compared with EUS-FNB tissues. The HTS drug sensitivity test showed clinical correlation between the ex vivo PDO response and the actual chemotherapeutic response of the study patients in the real world (13 out of 15 cases). In addition, whole-transcriptome sequencing identified candidate genes associated with nab-paclitaxel resistance, such as ITGB7, ANPEP, and ST3GAL1. CONCLUSIONS: This PDAC PDO platform allows several therapeutic drugs to be tested within a short time window and opens the possibility for timely personalized medicine as a "patient avatar model" in clinical practice.
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Carcinoma Ductal Pancreático , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Organoides , Neoplasias Pancreáticas , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Albúminas , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/genética , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Organoides/patología , Paclitaxel/administración & dosificación , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/genética , Medicina de Precisión/métodos , Estudios ProspectivosRESUMEN
BACKGROUND: Endoscopic papillectomy (EP) is an effective method to remove an ampulla of Vater (AoV) adenoma with minimal invasiveness. We reviewed the clinical outcomes and prognosis of patients undergoing EP, including tumor recurrence and adverse events. METHODS: A total of 196 patients who underwent EP from January 2004 to December 2017 were included. Clinical information was collected through electronic medical records, and risk factors to predict post-procedural bleeding were analyzed using a multivariate logistic regression model. RESULTS: A total of 93.9% patients (184/196) underwent complete resection. During the follow-up period, 14.7% patients (27/184) experienced tumor recurrence, and two of seven surgically resected tumors were malignant. A total of 45.4% patients (89/196) experienced adverse events related to EP. Delayed bleeding occurred in 16.3% of the patients (32/196), and they were all successfully treated with endoscopic hemostasis and conservative management. The most frequent site of delayed bleeding was the distal end of the papillary orifice, and 56.2% (18/32) patients of delayed bleeding were classified as having mild severity, the others had moderate severity. Familial adenomatous polyposis (FAP) [odds ratio (OR) = 3.80, 95% confidence interval (CI): 1.01-14.29; P < 0.05] and male sex (OR = 2.82, 95% CI: 1.04-7.63; P = 0.04) showed statistical significance in predicting delayed post-EP bleeding. CONCLUSIONS: EP for AoV adenoma was a highly effective and safe procedure. The risk of post-EP delayed bleeding was increased in patients with FAP syndrome and male patients, and post-EP bleeding occurred most commonly in the distal part of the AoV.
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Background: To evaluate the efficacy and optimal timing of local treatment in patients with borderline resectable (BR) or locally advanced pancreatic cancer (LAPC) treated with upfront FOLFIRINOX. Method: Between 2015 and 2020, 258 patients with pancreatic ductal adenocarcinoma (PDAC) were analysed. Treatment outcomes were compared between systemic treatment group (ST) and multimodality treatment groups (MT) using Kaplan-Meier curves and log-rank test. The MT were stratified as follows: FOLFIRINOX + radiation therapy (RT) (MT1), FOLFIRINOX + surgical resection (MT2), and FOLFIRINOX + RT + surgical resection (MT3). Results: With median follow-up period of 18 months, the 2-year overall survival (OS) for the ST was 22.0%, and it was significantly worse than MT (MT1, 46.3%; MT2, 65.7% and MT3; 90.2%; P < .001). The 2-year locoregional progression free survival (LRPFS) and overall PFS in ST were 10.7% and 7.0%, which were also significantly lower than those of MT (2-year LRPFS: MT1, 31.8%; MT2, 45.3%; MT3, 81.0%; 2-year overall PFS: MT1, 23.3%; MT2, 35.0%; MT3, 66.3%; P < .001). In time-varying multivariate Cox proportional hazard model, local treatment contributed to better treatment outcomes, with adjusted hazard ratios of 0.568 (95% confidence interval [CI], 0.398-0.811), 0.490 (95% CI, 0.331-0.726), and 0.656 (95% CI, 0.458-0.940) for OS, LRPFS, and overall PFS, respectively. The time window of 11-17 months after FOLFIRINOX appeared to demonstrate the maximal efficacy of local treatments in OS. Conclusions: Adding local treatment in BR/LAPC patients treated with upfront FOLFIRINOX seemed to contribute in improved treatment outcomes, and it showed maximal efficacy in OS when applied 11-17 months after the initiation of FOLFIRINOX. We suggest that administration of sufficient period of upfront FOLFIRINOX may intensify the efficacy of local treatments, and well controlled prospective trials are expected.
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Background: A regimen of gemcitabine, cisplatin, and nab-paclitaxel (GPA) has shown promising results in patients with advanced biliary tract cancer (aBTC). Objectives: This study aimed to evaluate the benefit of GPA compared to a regimen of gemcitabine plus cisplatin (GP) in patients with aBTC. Design: Retrospective study. Methods: Patients with aBTC who received first-line chemotherapy with GPA or GP regimen at the Samsung Medical Center between July 2020 and June 2022 were included. The primary endpoint was progression-free survival (PFS). Results: In all, 37 patients were treated with GPA and 43 patients with GP. The GPA group showed significantly longer median PFS [12.0 months (95% CI, 7.2-16.8)] compared to the GP group [5.5 months (95% CI, 3.7-7.4; p = 0.007)]. The median overall survival (OS) was also longer in the GPA group [18.7 months (95% CI, 13.7-23.7)] than in the GP group [10.7 months (95% CI, 1.5-19.9); p = 0.021]. First-line chemotherapy with GPA was associated with longer PFS, while metastatic disease at initial diagnosis and post-treatment increase in CA 19-9 level were associated with worse PFS. Conclusion: The GPA regimen improved the PFS of patients with aBTC compared to the GP regimen but showed no significant benefit in terms of OS after adjusting for confounding variables. Further large-scale studies are required to establish optimal indications for GPA.
Comparing new and standard chemotherapy treatments for advanced biliary tract cancer: a study of effectiveness and survival In this study, researchers at Samsung Medical Center investigated the effectiveness of two chemotherapy regimens for advanced biliary tract cancer (aBTC) from July 2020 to June 2022. The study compared a new treatment combination, gemcitabine, cisplatin, and nab-paclitaxel (GPA), against the standard treatment of gemcitabine and cisplatin (GP). The main focus was on progression-free survival (PFS) the time patients lived without their cancer worsening, and overall survival (OS) the total lifespan after treatment. A total of 37 patients received the GPA treatment, while 43 received the GP treatment. The results showed that patients on the GPA regimen had a longer median PFS of 12.0 months, compared to 5.5 months for those on the GP regimen. This significant difference suggested that GPA might be more effective in slowing cancer progression. Moreover, the median OS was also longer for patients treated with GPA (18.7 months) than for those with the GP regimen (10.7 months). These findings indicated that GPA not only delayed the progression of cancer but also potentially increased the overall survival time of patients. However, when accounting for other factors that could influence the results, the advantage of GPA in terms of overall survival became less clear. This suggests that while GPA is effective in delaying disease progression, its impact on extending the overall life expectancy of patients with aBTC is not definitive. Despite these promising findings, the researchers cautioned that the benefits of the GPA regimen in extending overall survival need further investigation. The study underscores the potential of GPA in improving outcomes for aBTC patients but also highlights the necessity for more comprehensive studies. These future studies are needed to confirm the optimal treatment for this challenging cancer type. This research is a step towards better understanding and managing aBTC, a cancer that currently has limited treatment options.
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BACKGROUND: Lysosomes are closely linked to autophagic activity, which plays a vital role in pancreatic ductal adenocarcinoma (PDAC) biology. The survival of PDAC patients is still poor, and the identification of novel genetic factors for prognosis and treatment is highly required to prevent PDAC-related deaths. This study investigated the germline variants related to lysosomal dysfunction in patients with PDAC and to analyze whether they contribute to the development of PDAC. METHODS: The germline putative pathogenic variants (PPV) in genes involved in lysosomal storage disease (LSD) was compared between patients with PDAC (n = 418) and healthy controls (n = 845) using targeted panel and whole-exome sequencing. Furthermore, pancreatic organoids from wild-type and KrasG12D mice were used to evaluate the effect of lysosomal dysfunction on PDAC development. RNA sequencing (RNA-seq) analysis was performed with established PDAC patient-derived organoids (PDOs) according to the PPV status. RESULTS: The PPV in LSD-related genes was higher in patients with PDAC than in healthy controls (8.13 vs. 4.26%, Log2 OR = 1.65, P = 3.08 × 10-3). The PPV carriers of LSD-related genes with PDAC were significantly younger than the non-carriers (mean age 61.5 vs. 65.3 years, P = 0.031). We further studied a variant of the lysosomal enzyme, galactosylceramidase (GALC), which was the most frequently detected LSD variant in our cohort. Autophagolysosomal activity was hampered when GALC was downregulated, which was accompanied by paradoxically elevated autophagic flux. Furthermore, the number of proliferating Ki-67+ cells increased significantly in pancreatic organoids derived from Galc knockout KrasG12D mice. Moreover, GALC PPV carriers tended to show drug resistance in both PDAC cell line and PDAC PDO, and RNA-seq analysis revealed that various metabolism and gene repair pathways were upregulated in PDAC PDOs harboring a GALC variant. CONCLUSIONS: Genetically defined lysosomal dysfunction is frequently observed in patients with young-onset PDAC. This might contribute to PDAC development by altering metabolism and impairing autophagolysosomal activity, which could be potentially implicated in therapeutic applications for PDAC.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Ratones , Animales , Persona de Mediana Edad , Proteínas Proto-Oncogénicas p21(ras) , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Células Germinativas/metabolismo , Lisosomas/metabolismo , Lisosomas/patología , Neoplasias PancreáticasRESUMEN
Several in vivo swine models of benign biliary stenosis (BBS) have been recently reported for preclinical studies of novel endoscopic techniques and devices. The aim of this study was to evaluate the efficacy and feasibility of large animal models of BBS by using intraductal radiofrequency ablation (RFA) assisted by guide wire. Six in vivo swine models were made by using an intraductal RFA for cauterization at 10 W, 80 °C, 90 s in the common bile duct (CBD). Endoscopic retrograde cholangiopancreatography (ERCP) was performed with cholangiography and histologic evaluation was done for the common bile duct. Blood tests were examined before, after, and at the final follow-up. Guide wire assisted RFA electrode produced BBS in all (6/6, 100%) animal models without severe complications. Fluoroscopy findings at 2 weeks after intraductal RFA in every model revealed BBS in the common bile duct. In histologic evaluations, fibrosis and chronic inflammatory changes were noted. After the procedure, ALP, GGT, and CRP were elevated and decreased after an appropriate drain. A swine model of BBS is developed by inducing intraductal thermal injury using intraductal RFA assisted by guide wire. This novel technique for inducing BBS in swine is effective and feasible.
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Ablación por Catéter , Colestasis , Ablación por Radiofrecuencia , Porcinos , Animales , Constricción Patológica/patología , Estudios de Factibilidad , Ablación por Catéter/métodos , Colestasis/complicaciones , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Ablación por Radiofrecuencia/efectos adversosRESUMEN
Background: In patients with BD-IPMN, surgical indications have been focused on finding malignant lesions (HGD, high-grade dysplasia/IC, invasive carcinoma). The aim of this study was to compare the preoperative factors that distinguish HGD from LGD (low-grade dysplasia) and HGD from IC to find the optimal pathologic target for surgery according to individuals, considering surgical risks and outcomes. Methods: We retrospectively analyzed 232 patients with BD-IPMN diagnosed based on pathology after surgery and preoperative images. The primary outcome was identifying preoperative factors distinguishing HGD from LGD, and HGD from IC. Results: In patients with LGD/HGD, a solid component or an enhancing mural nodule ≥ 5 mm (OR = 9.29; 95% CI: 3.3−54.12; p < 0.000) and thickened/enhancing cyst walls (OR = 6.95; 95% CI: 1.68−33.13; p = 0.008) were associated with HGD. In patients with malignant lesions (HGD/IC), increased serum CA 19-9 (OR = 12.59; 95% CI: 1.81−87.44; p = 0.006) was associated with IC. Conclusions: The predictive factors for HGD were the presence of a solid component or an enhancing mural nodule ≥ 5 mm and thickened/enhancing cyst walls compared with LGD, and if accompanied by increased CA 19-9, it might be necessary to urgently evaluate the lesion due to the possibility of progression to IC. Based on this finding, we need to find HGD as the optimal pathologic target for surgery to improve survival in low-surgical-risk patients, and IC could be assumed to be the optimal pathologic target for surgery in high-surgical-risk patients because of high morbidity and mortality associated with surgery.
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Pancreaticobiliary tract cancer has a poor prognosis with unmet needs in a new target treatment. Some studies have reported that an enhancement of T-cell immunity is associated with a good prognosis. The aim of this study is to investigate the immunoprofile as a prognostic marker of pancreaticobiliary tract cancers. Unresectable pancreatic ductal adenocarcinoma (PDAC, n = 80) and biliary tract cancer (BTC, n = 74) diagnosed between January 2012 and December 2018 in Samsung Medical Center were analyzed. Expression levels of CD8, FOXP3, PD-1, PD-L1, and CXCL13 in PDAC and BTC tissue samples were examined with immunohistochemical staining, which was evaluated with various clinical factors. In PDAC, higher degree of PD-L1 expression was significantly associated with shorter overall survival (OS) (p = 0.0095). On the other hand, higher infiltrations of PD-1+ immune cells (p = 0.0002) and CD8+ T cells (p = 0.0067) were associated with longer OS. In BTC, higher FOXP3+ (p = 0.0343) and CD8+ (p = 0.0028) cell infiltrations were associated with better survival. Low infiltration of CD8+ (p = 0.0148), FOXP3+ (p = 0.0208), PD-1+ (p = 0.0318) cells in PDAC, and FOXP3+ cells (p = 0.005) in BTC were considerably related to metastasis. In a combined evaluation of clinical factors and immunoprofiles, univariate analysis revealed that operation after chemotherapy (p < 0.0001), mass size (p = 0.0004), metastasis (p = 0.006), PD-L1 (p < 0.0001), PD-1 (p = 0.003) and CD8 (p = 0.0063) was significantly associated with OS in PDAC, and CD8 (p = 0.007) was statistically related to OS in BTC. In multivariate analysis, prognostic factors were operation after chemotherapy (p = 0.021) in PDAC and CD8 (p = 0.037) in BTC. Therefore, immunoprofile analysis of cells expressing CD8, FOXP3, PD-1, and PD-L1 might have prognostic values in patients with pancreaticobiliary tract cancers.
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Neoplasias Gastrointestinales , Neoplasias Pancreáticas , Humanos , Pronóstico , Antígeno B7-H1/metabolismo , Linfocitos T CD8-positivos , Receptor de Muerte Celular Programada 1 , Neoplasias Pancreáticas/patología , Neoplasias Gastrointestinales/patología , Factores de Transcripción Forkhead/metabolismo , Linfocitos Infiltrantes de TumorRESUMEN
Background/Aims: Cholangiocarcinoma frequently recurs even after curative resection. Expression levels of proteins such as epidermal growth factor receptor (EGFR), Snail, epithelial cadherin (E-cadherin), and interleukin-6 (IL-6) examined by immunohistochemistry have been studied as potential prognostic factors for cholangiocarcinoma. The aim of this study was to investigate significant factors affecting the prognosis of resectable cholangiocarcinoma. Methods: Ninety-one patients who underwent surgical resection at Samsung Medical Center for cholangiocarcinoma from 1995 to 2013 were included in this study. Expression levels of E-cadherin, Snail, IL-6, membranous EGFR, and cytoplasmic EGFR were analyzed by immunohistochemistry using tissue microarray blocks made from surgical specimens. Results: Patients with high levels of membranous EGFR in tissue microarrays had significantly shorter overall survival (OS) and disease-free survival (DFS): high membranous EGFR (score 0-2) 38.0 months versus low membranous EGFR (score 3) 14.4 months (p=0.008) and high membranous EGFR (score 0-2) 23.2 months versus low membranous EGFR (score 3) 6.1 months (p=0.004), respectively. On the other hand, E-cadherin, Snail, cytoplasmic EGFR, and IL-6 did not show significant association with OS or DFS. Patients with distant metastasis had significantly higher IL-6 levels than those with locoregional recurrence (p=0.01). Conclusions: This study showed that overexpression of membranous EGFR was significantly associated with shorter OS and DFS in surgically resected bile duct cancer patients. In addition, higher IL-6 expression was a predictive marker for recurrence in cholangiocarcinoma patients with distant organ metastasis after surgical resection.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Pronóstico , Interleucina-6/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Colangiocarcinoma/cirugía , Neoplasias de los Conductos Biliares/cirugía , Cadherinas/análisis , Cadherinas/metabolismo , Receptores ErbB/análisis , Receptores ErbB/metabolismo , Conductos Biliares Intrahepáticos , InmunoensayoRESUMEN
Background/Purpose: This study aimed to evaluate the clinical outcomes of stereotactic body proton beam therapy (SBPT) for pancreatic cancer. Methods: This retrospective study included 49 patients who underwent SBPT for pancreatic cancer between 2017 and 2020. Survival outcomes, bowel-related toxicities, and failure patterns were analysed. SBPT was performed after induction chemotherapy in 44 (89.8%) patients. The dose-fractionation scheme included 60 gray (Gy) relative biological effectiveness (RBE) in five fractions (n = 42, 85.7%) and 50 GyRBE in five fractions (n = 7, 14.3%). The median follow-up was 16.3 months (range, 1.8−45.0 months). Results: During follow-up, the best responses were complete response, partial response, and stable disease in four (8.2%), 13 (26.5%), and 31 (63.3%) patients, respectively. The 2-year overall survival, progression-free survival, and local control (LC) rates were 67.6%, 38.0%, and 73.0%, respectively. Grade ≥ 3 gastroduodenal (GD) toxicity occurred in three (6.1%) patients. Among them, one patient underwent endoscopic haemostasis. The other two patients received surgical management. They were followed up without disease progression for >30 months after SBPT. Overall, there was no significant dosimetric difference between the grade ≥ 2 and lower toxicity groups. Conclusions: SBPT provides relatively high LC rates with acceptable toxicities in pancreatic cancer.
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BACKGROUND: The differential diagnosis of immunoglobulin G4-sclerosing cholangitis (IgG4-SC) from primary sclerosing cholangitis (PSC) or cholangiocarcinoma (CCA) is important. In this study, we aimed to find the best combinations of serum IgG subclasses and IgG4 levels for differentiating IgG4-SC from PSC or CCA. METHODS: In total, 31 patients with IgG4-SC, 27 patients with PSC, and 40 patients with CCA were enrolled from 2003 to 2017 at a single tertiary referral center. We retrospectively assessed the IgG4, IgG4/IgG1, IgG4/(IgG1+IgG3), and (IgG4+IgG2)/(IgG1+IgG3) in each of the patients. ROC curves were established to obtain the optimal cutoff value for each parameter. McNemar's test was used to compare the sensitivities, specificities, and accuracies of diagnostic algorithms. RESULTS: In differentiating IgG4-SC from PSC, the accuracies of IgG4/IgG1 ≥ 0.087 and of IgG4/(IgG1+IgG3) ≥ 0.081 were significantly higher than that of IgG4 ≥ 135 mg/dL alone (78% vs. 66%, p = 0.025). Serum IgG4 ≥ 52 mg/dL showed the best accuracy for differentiation of IgG4-SC from CCA, with a sensitivity and specificity of 80% and 82%, respectively, but this was statistically not significant (p = 0.405). CONCLUSIONS: The serum IgG4/IgG1 or IgG4/(IgG1+IgG3) level may help to differentiate IgG4-SC from PSC. IgG4 alone is the most accurate serologic marker for the differentiation of IgG4-SC from CCA.
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Background/Aims: As pancreatic mucinous cystic neoplasms (MCNs) are considered premalignant lesions, the current guidelines recommend their surgical resection. We aimed to investigate the concordance between preoperative and postoperative diagnoses and evaluate preoperative clinical parameters that could predict the malignant potential of MCNs. Methods: Patients who underwent surgical resection at Samsung Medical Center for pancreatic cystic lesions and whose pathology was confirmed to be MCN, between July 2000 and December 2017, were retrospectively analyzed. Results: Among a total of 132 patients 99 (75%) were diagnosed with MCN preoperatively. The most discordant preoperative diagnosis was an indeterminate pancreatic cyst. The proportion of male patients was higher (24.2% vs 7.1%, p=0.05) in the diagnosis-discordance group and the presence of worrisome features in radiologic imaging studies, such as wall thickening/enhancement (12.1% vs 37.4%, p=0.02) or solid component/mural nodule (3.0% vs 27.3%, p=0.02), was lower in the diagnosis-discordance group. The presence of symptoms (57.7% vs 34.9%, p=0.02), tumor size greater than 4 cm (80.8% vs 55.7%, p=0.04), and radiologic presence of a solid component/mural nodule (42.3% vs 16.0%, p=0.01) or duct dilatation (19.2% vs 6.6%, p=0.01) were significantly associated with malignant MCNs. Conclusions: In our study, the overall diagnostic concordance rate was confirmed to be 75%, and our findings suggest that MCNs have a low malignancy potential when they are less than 4 cm in size, are asymptomatic and lack worrisome features on preoperative images.
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Cistoadenoma Mucinoso , Quiste Pancreático , Neoplasias Pancreáticas , Cistoadenoma Mucinoso/diagnóstico , Humanos , Masculino , Páncreas/patología , Quiste Pancreático/diagnóstico por imagen , Quiste Pancreático/patología , Quiste Pancreático/cirugía , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Circulating tumor cells (CTCs) have emerged as liquid biopsy biomarker providing non-invasive assessment of cancer progression and biology. We investigated whether longitudinal analysis of CTCs could monitor disease progression, response to chemotherapy, and survival in patients with unresectable pancreatic ductal adenocarcinoma (PDAC). A total of 52 patients with PDAC were prospectively enrolled in this study. Peripheral blood samples were serially collected at the time of diagnosis and after chemotherapy with clinical assessments. CTCs were isolated through a centrifugal microfluidic disc, enumerated with immunostaining against Epithelial cell adhesion molecule (EpCAM), Cytokeratin (CK), Plectin-1 and CD45, and identified by an automated imaging system. One or more CTCs were detected in 84.62% patients with unresectable PDAC at the time of diagnosis. CTC numbers were not statistically different across tumor sizes, location and metastatic sites. The absolute number of CTCs after chemotherapy was inversely related to overall survival (OS), and the decreased number of CTCs after chemotherapy was significantly associated with longer OS in patients with PDAC. Identifying CTCs and monitoring CTC changes after chemotherapy could be a useful prognostic marker for survival in patients with unresectable PDACs.
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BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) are commonly used diagnostic modalities in biliary strictures. We compared the diagnostic yield of EUS and ERCP-based tissue sampling in intrinsic biliary strictures without extrinsic mass outside the bile duct. METHODS: A total of 85 patients who underwent ERCP and EUS for diagnosis of suspected biliary strictures confined to the bile duct were analyzed retrospectively at Samsung Medical Center, Seoul, Korea, between 2010 and 2018. RESULTS: Seventy-one patients were diagnosed with malignancy and 14 patients were diagnosed with benign strictures. EUS-based tissue sampling was more sensitive and accurate than ERCP-based tissue sampling (p = 0.038). The overall sensitivity and accuracy were 67.6% (95% confidence interval (CI) 56.1-77.3) and 72.9% (95% CI 62.7-81.2) for ERCP-based sampling, and 80.3% (95% CI 69.6-87.9) and 83.5% (95% CI 74.2-89.9) for EUS-based sampling, respectively. EUS-based sampling was superior to ERCP-based sampling in distal bile duct strictures (accuracy: 87.0% vs. 72.5%, p = 0.007), but not in perihilar strictures. In cases without intraductal mass, EUS-based tissue sampling was also superior to ERCP-based sampling (accuracy: 83.3% vs. 69.7%, p = 0.029), but not in cases with mass. CONCLUSION: EUS-based tissue sampling was superior to ERCP-based method in intrinsic biliary stricture with no mass outside the bile duct, particularly in those without intraductal mass or those with strictures located in distal bile duct. Therefore, EUS-based sampling should be considered for making a pathological diagnosis of suspected distal bile duct strictures even in lesions without definite mass.
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Enfermedades de los Conductos Biliares/diagnóstico por imagen , Conductos Biliares/diagnóstico por imagen , Colangiopancreatografia Retrógrada Endoscópica/métodos , Colestasis/diagnóstico por imagen , Ultrasonografía Intervencional/métodos , Adulto , Anciano , Anciano de 80 o más Años , Constricción Patológica/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
The aim of this study was to investigate the clinical utility of minimal specimens acquired from endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) and perform targeted deep sequencing as a prognosis prediction tool for pancreatic ductal adenocarcinoma (PDAC). A total of 116 specimens with pathologically confirmed PDAC via EUS-FNB were tested using CancerSCAN® panel for a customized targeted deep sequencing. Clinical prognostic factors significantly associated with survival in PDACs were as follows: stage, tumor mass size, tumor location, metastasis, chemotherapy, and initial CA19-9 level. A total of 114 patients (98.3%) had at least a single genetic alteration, and no mutations were detected in two patients, although they were qualified for the targeted deep sequencing. The frequencies of major gene mutations responsible for PDACs were KRAS 90%, CDKN2A 31%, TP53 77%, and SMAD4 29%. A somatic point mutation of NF1, copy number alteration of SMAD4, and loss-of-function of CDKN2A were significantly associated genetic factors for overall survival. Moreover, BRCA2 point mutation was related to liver metastasis. Finally, a clinico-genomic model was developed to estimate the prognosis of patients with PDAC based on clinical parameters and genetic alterations affecting survival in patients; 20 single nucleotide variants and three copy number variations were selected. Targeted deep sequencing on minimal specimens of PDACs was performed, and it was applied to establish a clinico-genomic model for prognosis prediction.
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PURPOSE: Erlotinib has been the only targeted agent to show significantly improved outcomes in pancreatic adenocarcinoma when combined with gemcitabine. We aimed to evaluate whether the addition of oxaliplatin to a combination gemcitabine/erlotinib treatment conferred a clinical benefit in patients with locally advanced unresectable or metastatic pancreatic cancer. MATERIALS AND METHODS: Chemotherapy-naïve patients with locally advanced or metastatic pancreatic cancer were randomly assigned to receive GEMOX-T [gemcitabine 1000 mg/m² and oxaliplatin 50 mg/m² on day 1 (D1) and D8 plus erlotinib 100 mg daily for 3 weeks] or GT (gemcitabine 1000 mg/m² on D1 and D8 plus erlotinib 100 mg daily for 3 weeks). The primary endpoint was the overall response rate (ORR). RESULTS: Between 2013 and 2016, 65 patients were assigned to a treatment group (33 in the GEMOX-T arm, 32 in the GT arm). The ORR was 18.2% [95% confidence interval (CI), 8.82-27.58] in the GEMOX-T arm and 6.2% (95% CI, 0.34-12.06) in the GT arm (p=0.051). The disease control rate was significantly superior in the GEMOX-T arm compared to the GT arm (72.7% vs. 43.8%, p=0.019). After a median follow-up of 19.7 months, the median progression-free survival (PFS) was 3.9 months for the GEMOX-T arm and 1.4 months for the GT arm (p=0.033). However, this did not translate to an improvement in overall survival. The most common grade 3 or higher hematologic adverse events were neutropenia (16.9%) and anemia (13.8%). CONCLUSION: The addition of oxaliplatin to a first-line gemcitabine/erlotinib regimen demonstrated higher response rates and significantly improved PFS in patients with locally advanced or metastatic pancreatic cancer.
Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Desoxicitidina/análogos & derivados , Clorhidrato de Erlotinib/efectos adversos , Humanos , Oxaliplatino/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Resultado del Tratamiento , GemcitabinaRESUMEN
Background: Clonorchis sinensis (CS) infection is considered a group 1 carcinogen of cholangiocarcinoma (CCA). There were very few studies regarding clinical characteristics of CS-associated CCA (CACC). This study aimed to investigate clinical characteristics of patients with CCA with or without CS infection. Methods: A total of 367 patients diagnosed with CCA who underwent diagnostic tests for CS infection were enrolled. CS infection was defined as follows: at least one positive serum ELISA test, skin test, stool microscopy, or bile microscopy. Results: There were 95 (26%) patients with CS infections. The median follow-up duration was 14.9 months (range, 6.07-36.17). The following significant differences were noted among patients with CACC compared to non-CACC; diagnosis at younger age (median 62 years vs. 65 years, p = 0.018), higher male to female ratio (83.2 vs. 61.8%, p < 0.001), and residence in CS-endemic area (46.3 vs. 25.4%, p = 0.014). Univariate analysis of prognostic factors indicated that tumor location, curative resection, tumor stage, and laboratory tests including CA 19-9, CEA, and bilirubin were significantly associated with overall survival, but CS infection was not. In multivariate analysis, tumor location, CEA, curative resection and tumor stage were identified as independent prognostic factors. Among patients under age 64, CACC group had lower survival rate than non-CACC group (p = 0.022). Conclusions: CACC had the following significant characteristics compared to non-CACC; diagnosis at younger age, higher male to female ratio, higher prevalence in CS endemic areas and poorer overall survival in patients under age 64.
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Background/Aims: For the management of hilar malignant biliary obstruction (HMBO), endoscopic biliary drainage (EBD) is preferred over percutaneous transhepatic biliary drainage (PTBD) because of its convenience. However, there is no established guideline for malignant hilar obstruction that requires multiple stenting. In this study, we compared the efficacy of bilateral metal stents (BMS) versus multiple plastic stents (MPS). Methods: In this retrospective study, we analyzed 102 patients who underwent EBD with either BMS or MPS due to HMBO caused by hilar cholangiocarcinoma between 1996 and 2018 at Samsung Medical Center. We compared the successful drainage rates, cholangitis events, overall complications, mortality, and conversion rates to PTBD between the two groups. Results: The successful drainage rates in the BMS group and the MPS group were 71.4% (25/35) and 65.6% (44/67), respectively, with no significant difference. The MPS group had a higher cholangitis risk (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.21 to 3.58) and higher 6-month mortality (HR, 2.91; 95% CI, 1.26 to 6.71) than the BMS group. There were no significant differences in overall complications or the conversion rate to PTBD between the groups. Conclusions: In patients with malignant HMBO, the BMS group showed better outcomes in terms of the cholangitis rate and 6-month mortality than the MPS group. Therefore, if possible, bilateral metal stenting is recommended for HMBO caused by hilar cholangiocarcinoma.