We investigated true indication of neoadjuvant therapy (NAT) in resectable pancreatic cancer and the optimal surgical timing in borderline resectable pancreatic cancer.
Methods
A total of 687 patients with resectable or borderline resectable pancreatic cancer were enrolled. Survival analysis was performed by intention-to-treat analysis and propensity score matching (PSM) was conducted.
Results
In resectable disease, the NAT group showed better overall survival (OS) compared with the upfront group. Multivariate analysis identified CA19-9 level (≥100 U/mL) and lymph node metastasis to be prognostic factors, and a tumor size of 25 mm was the optimal cut-off value to predict lymph node metastasis. There was no significant survival difference between patients with a tumor size ≤25 mm and CA19-9 < 100 U/mL and those in the NAT group. In borderline resectable disease, OS in the NAT group was significantly better than that in the upfront group. CEA (≥5 ng/mL) and CA19-9 (≥100 U/mL) were identified as prognostic factors; however, the OS of patients fulfilling these factors was worse than that of the NAT group.
Conclusions
NAT could be unnecessary in patients with tumor size ≤25 mm and CA19-9 < 100 U/mL in resectable disease. In borderline resectable disease, surgery should be delayed until tumor marker levels are well controlled.
{"title":"Reconsideration of the clinical impact of neoadjuvant therapy in resectable and borderline resectable pancreatic cancer: A dual-institution collaborative clinical study","authors":"Suguru Yamada , Daisuke Hashimoto , Tomohisa Yamamoto , So Yamaki , Kenji Oshima , Kenta Murotani , Mitsugu Sekimoto , Akimasa Nakao , Sohei Satoi","doi":"10.1016/j.pan.2024.03.012","DOIUrl":"10.1016/j.pan.2024.03.012","url":null,"abstract":"<div><h3>Purpose</h3><p>We investigated true indication of neoadjuvant therapy (NAT) in resectable pancreatic cancer and the optimal surgical timing in borderline resectable pancreatic cancer.</p></div><div><h3>Methods</h3><p>A total of 687 patients with resectable or borderline resectable pancreatic cancer were enrolled. Survival analysis was performed by intention-to-treat analysis and propensity score matching (PSM) was conducted.</p></div><div><h3>Results</h3><p>In resectable disease, the NAT group showed better overall survival (OS) compared with the upfront group. Multivariate analysis identified CA19-9 level (≥100 U/mL) and lymph node metastasis to be prognostic factors, and a tumor size of 25 mm was the optimal cut-off value to predict lymph node metastasis. There was no significant survival difference between patients with a tumor size ≤25 mm and CA19-9 < 100 U/mL and those in the NAT group. In borderline resectable disease, OS in the NAT group was significantly better than that in the upfront group. CEA (≥5 ng/mL) and CA19-9 (≥100 U/mL) were identified as prognostic factors; however, the OS of patients fulfilling these factors was worse than that of the NAT group.</p></div><div><h3>Conclusions</h3><p>NAT could be unnecessary in patients with tumor size ≤25 mm and CA19-9 < 100 U/mL in resectable disease. In borderline resectable disease, surgery should be delayed until tumor marker levels are well controlled.</p></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140318891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.pan.2024.03.004
Filippo Nozzoli , Martina Catalano , Luca Messerini , Fabio Cianchi , Romina Nassini , Francesco De Logu , Luigi Francesco Iannone , Filippo Ugolini , Sara Simi , Daniela Massi , Pierangelo Geppetti , Giandomenico Roviello
Background/objectives
Perineural invasion (PNI), classified according to its presence or absence in tumor specimens, is recognized as a poor prognostic factor in pancreatic ductal adenocarcinoma (PDAC) patients. Herein, we identified five histological features of PNI and investigated their impact on survival outcomes of PDAC resected patients.
Methods
Five histopathological features of PNI (diameter, number, site, sheath involvement, and mitotic figures within perineural invasion) were combined in an additional final score (ranging from 0 to 8), and clinical data of PDAC patients were retrospectively analyzed. PNI + patients were stratified in two categories according to the median score value (<6 and ≥ 6, respectively). Impact of PNI on disease-free survival (DFS) and overall survival (OS) were analyzed.
Results
Forty-five patients were enrolled, of whom 34 with PNI (PNI+) and 11 without PNI (PNI-). The DFS was 11 months vs. not reached (NR) (p = 0.258), while the OS was 19 months vs. NR (p = 0.040) in PNI+ and PNI- patients, respectively. A ≥6 PNI was identified as an independent predictor of worse OS vs. <6 PNI + patients (29 vs. 11 months, p < 0.001) and <6 PNI+ and PNI- patients (43 vs. 11 months, p < 0.001). PNI ≥6 was an independent negative prognostic factor of DFS vs. <6 PNI+ and PNI- patients (13 vs. 6 months, p = 0.022).
Conclusions
We report a PNI scoring system that stratifies surgically-treated PDAC patients in a graded manner that correlates with patient prognosis better than the current dichotomous (presence/absence) definition. However, further and larger studies are needed to support this PNI scoring system.
{"title":"Perineural invasion score system and clinical outcomes in resected pancreatic cancer patients","authors":"Filippo Nozzoli , Martina Catalano , Luca Messerini , Fabio Cianchi , Romina Nassini , Francesco De Logu , Luigi Francesco Iannone , Filippo Ugolini , Sara Simi , Daniela Massi , Pierangelo Geppetti , Giandomenico Roviello","doi":"10.1016/j.pan.2024.03.004","DOIUrl":"10.1016/j.pan.2024.03.004","url":null,"abstract":"<div><h3>Background/objectives</h3><p>Perineural invasion (PNI), classified according to its presence or absence in tumor specimens, is recognized as a poor prognostic factor in pancreatic ductal adenocarcinoma (PDAC) patients. Herein, we identified five histological features of PNI and investigated their impact on survival outcomes of PDAC resected patients.</p></div><div><h3>Methods</h3><p>Five histopathological features of PNI (diameter, number, site, sheath involvement, and mitotic figures within perineural invasion) were combined in an additional final score (ranging from 0 to 8), and clinical data of PDAC patients were retrospectively analyzed. PNI + patients were stratified in two categories according to the median score value (<6 and ≥ 6, respectively). Impact of PNI on disease-free survival (DFS) and overall survival (OS) were analyzed.</p></div><div><h3>Results</h3><p>Forty-five patients were enrolled, of whom 34 with PNI (PNI+) and 11 without PNI (PNI-). The DFS was 11 months <em>vs.</em> not reached (NR) (<em>p</em> = 0.258), while the OS was 19 months <em>vs.</em> NR (<em>p</em> = 0.040) in PNI+ and PNI- patients, respectively. A ≥6 PNI was identified as an independent predictor of worse OS <em>vs.</em> <6 PNI + patients (29 <em>vs.</em> 11 months, <em>p</em> < 0.001) and <6 PNI+ and PNI- patients (43 <em>vs.</em> 11 months, <em>p</em> < 0.001). PNI ≥6 was an independent negative prognostic factor of DFS <em>vs</em>. <6 PNI+ and PNI- patients (13 <em>vs</em>. 6 months, <em>p</em> = 0.022).</p></div><div><h3>Conclusions</h3><p>We report a PNI scoring system that stratifies surgically-treated PDAC patients in a graded manner that correlates with patient prognosis better than the current dichotomous (presence/absence) definition. However, further and larger studies are needed to support this PNI scoring system.</p></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1424390324000656/pdfft?md5=ddf8711744afb64ae0a897b4531c38cf&pid=1-s2.0-S1424390324000656-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140166453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.pan.2024.03.013
Yeshong Park , Yeon Bi Han , Jinju Kim , MeeYoung Kang , Boram Lee , Eun Sung Ahn , Saemi Han , Haeryoung Kim , Hee-Young Na , Ho-Seong Han , Yoo-Seok Yoon
Background
Although various pathological grading systems are available for evaluating the response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant therapy (NAT), their prognostic value has not been thoroughly validated. This study examined whether microscopic tumor mapping of post-NAT specimens could predict tumor recurrence.
Methods
This prospective study enrolled 52 patients who underwent pancreaticoduodenectomy after NAT for PDAC between 2019 and 2021. Microscopic mapping was performed to identify residual tumor loci within the tumor bed using 4 mm2 pixels. Patients were divided into small extent (SE; n = 26) and large extent (LE; n = 26) groups using a cutoff value of 226 mm2. The diagnostic performance for predicting tumor recurrence was evaluated using receiver operating characteristic (ROC) curves.
Results
Carbohydrate antigen 19-9 levels were normalised after NAT in more patients in the SE group (SE 21 [80.8%] vs. LE 13 [50.0%]; P = 0.041). Tumor size (P < 0.001), T stage (P < 0.001), positive lymph node yield (P = 0.024), and perineural invasion rate (P = 0.018) were significantly greater in the LE group. The 3-year disease-free survival rate was significantly lower in the LE group (SE 83.3% vs. LE 50.0%, P = 0.004). The area under the ROC curve for mapping extent was 0.743, which was greater than that of the other tumor response scoring systems.
Conclusions
Microscopic tumor mapping of the residual tumor in post-NAT specimens is a significant predictor of post-surgical recurrence, and offers better prognostic performance than the current grading systems.
背景：尽管有多种病理分级系统可用于评估胰腺导管腺癌（PDAC）对新辅助治疗（NAT）的反应，但其预后价值尚未得到彻底验证。本研究探讨了新辅助治疗后标本的显微肿瘤图谱能否预测肿瘤复发：这项前瞻性研究纳入了2019年至2021年间因PDAC接受NAT后胰十二指肠切除术的52名患者。使用 4 平方毫米像素进行显微绘图，以确定肿瘤床内的残余肿瘤位置。以226平方毫米为临界值，将患者分为小范围组（SE；n = 26）和大范围组（LE；n = 26）。使用接收器操作特征曲线（ROC）评估了预测肿瘤复发的诊断性能：结果：更多 SE 组患者（SE 21 [80.8%] vs. LE 13 [50.0%]; P = 0.041）在 NAT 后碳水化合物抗原 19-9 水平恢复正常。肿瘤大小（PNAT 术后标本中残留肿瘤的显微镜下肿瘤图谱是手术后复发的重要预测指标，其预后效果优于目前的分级系统。
{"title":"Microscopic tumor mapping of post-neoadjuvant therapy pancreatic cancer specimens to predict post-surgical recurrence: A prospective cohort study","authors":"Yeshong Park , Yeon Bi Han , Jinju Kim , MeeYoung Kang , Boram Lee , Eun Sung Ahn , Saemi Han , Haeryoung Kim , Hee-Young Na , Ho-Seong Han , Yoo-Seok Yoon","doi":"10.1016/j.pan.2024.03.013","DOIUrl":"10.1016/j.pan.2024.03.013","url":null,"abstract":"<div><h3>Background</h3><p>Although various pathological grading systems are available for evaluating the response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant therapy (NAT), their prognostic value has not been thoroughly validated. This study examined whether microscopic tumor mapping of post-NAT specimens could predict tumor recurrence.</p></div><div><h3>Methods</h3><p>This prospective study enrolled 52 patients who underwent pancreaticoduodenectomy after NAT for PDAC between 2019 and 2021. Microscopic mapping was performed to identify residual tumor loci within the tumor bed using 4 mm<sup>2</sup> pixels. Patients were divided into small extent (SE; <em>n</em> = 26) and large extent (LE; <em>n</em> = 26) groups using a cutoff value of 226 mm<sup>2</sup>. The diagnostic performance for predicting tumor recurrence was evaluated using receiver operating characteristic (ROC) curves.</p></div><div><h3>Results</h3><p>Carbohydrate antigen 19-9 levels were normalised after NAT in more patients in the SE group (SE 21 [80.8%] vs. LE 13 [50.0%]; <em>P</em> = 0.041). Tumor size (<em>P</em> < 0.001), T stage (<em>P</em> < 0.001), positive lymph node yield (<em>P</em> = 0.024), and perineural invasion rate (<em>P</em> = 0.018) were significantly greater in the LE group. The 3-year disease-free survival rate was significantly lower in the LE group (SE 83.3% vs. LE 50.0%, <em>P</em> = 0.004). The area under the ROC curve for mapping extent was 0.743, which was greater than that of the other tumor response scoring systems.</p></div><div><h3>Conclusions</h3><p>Microscopic tumor mapping of the residual tumor in post-NAT specimens is a significant predictor of post-surgical recurrence, and offers better prognostic performance than the current grading systems.</p></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140331962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.pan.2024.04.001
Wentong Mei , Xiuli Zhang , Mengya Niu , Liang Li , Xiaoyu Guo , Gang Wang , Stephen Pandol , Li Wen , Feng Cao
Background
Store-operated Ca2+ entry (SOCE) mediated by ORAI1 channel plays a crucial role in acute pancreatitis (AP). Macrophage is an important regulator in amplifying pancreatic tissue damage, but little is known about the role of ORAI1 in macrophages. In this study, we examined the effects of macrophage-specific ORAI1 on pancreatic tissue damage in AP.
Method
Myeloid-specific Orai1 deficient mice was generated by crossing a LysM-Cre mouse line with Orai1f/f mice. Bone marrow-derived macrophages (BMDMs) were isolated, cultured, and stimulated to induce M1 or M2 macrophage polarization. Intracellular Ca2+ signals were measured by time-lapse confocal microscope imaging, with a Ca2+ indicator (Fluo 4). Experimental AP was induced by hourly intraperitoneal injections of caerulein or retrograde biliopancreatic infusion of sodium taurocholate. Pancreatic tissue damage was assessed by histopathological scoring and immunostaining. Sepsis was induced by intraperitoneal injection of lipopolysaccharide; organ damage and serum pro-inflammatory cytokines were measured.
Result
Myeloid-specific Orai1 deletion exhibited minimal effect on SOCE in M0 macrophages and promoted M2 macrophage polarization ex vivo. Myeloid-specific Orai1 deletion did not affect pancreatic tissue damage, nor neutrophil or macrophage infiltration in two models of AP. Similarly, myeloid-specific Orai1 deletion did not influence overall survival rate in a model of sepsis, nor lung, kidney, and liver damage; while serum pro-inflammatory cytokines, including IL-6, TNF-α, and IL-1β were higher in Orai1ΔLysM mice, but were largely reduced in mice with Orai1 inhibitor.
Conclusion
Our data suggest that ORAI1 may not be a predominant SOCE channel in macrophages and play a limited role in mediating pancreatic tissue damage in AP.
由 ORAI1 通道介导的贮存操作钙离子通道（SOCE）在急性胰腺炎（AP）中起着至关重要的作用。巨噬细胞是扩大胰腺组织损伤的重要调节因子，但人们对 ORAI1 在巨噬细胞中的作用知之甚少。本研究探讨了巨噬细胞特异性 ORAI1 对 AP 中胰腺组织损伤的影响。通过与 LysM-Cre 小鼠品系杂交产生了骨髓特异性缺陷小鼠。分离、培养骨髓源性巨噬细胞（BMDMs）并刺激其诱导M1或M2巨噬细胞极化。使用 Ca 指示剂（Fluo 4）通过延时共聚焦显微镜成像测量细胞内 Ca 信号。通过每小时腹腔注射考来烯胺或逆行胆胰灌注牛磺胆酸钠诱导实验性 AP。胰腺组织损伤通过组织病理学评分和免疫染色进行评估。通过腹腔注射脂多糖诱发败血症；测量器官损伤和血清促炎细胞因子。髓系特异性缺失对M0巨噬细胞的SOCE影响极小，但促进了M2巨噬细胞的极化。在两种 AP 模型中，髓系特异性缺失不会影响胰腺组织损伤，也不会影响中性粒细胞或巨噬细胞浸润。同样，髓系特异性缺失也不影响败血症模型的总体存活率，也不影响肺、肾和肝损伤；而小鼠血清中的促炎细胞因子，包括IL-6、TNF-α和IL-1β较高，但在使用Orai1抑制剂的小鼠中则大大降低。我们的数据表明，ORAI1 可能不是巨噬细胞中主要的 SOCE 通道，在 AP 中介导胰腺组织损伤的作用有限。
{"title":"Deletion of myeloid-specific Orai1 calcium channel does not affect pancreatic tissue damage in experimental acute pancreatitis","authors":"Wentong Mei , Xiuli Zhang , Mengya Niu , Liang Li , Xiaoyu Guo , Gang Wang , Stephen Pandol , Li Wen , Feng Cao","doi":"10.1016/j.pan.2024.04.001","DOIUrl":"10.1016/j.pan.2024.04.001","url":null,"abstract":"<div><h3>Background</h3><p>Store-operated Ca<sup>2+</sup> entry (SOCE) mediated by ORAI1 channel plays a crucial role in acute pancreatitis (AP). Macrophage is an important regulator in amplifying pancreatic tissue damage, but little is known about the role of ORAI1 in macrophages. In this study, we examined the effects of macrophage-specific ORAI1 on pancreatic tissue damage in AP.</p></div><div><h3>Method</h3><p>Myeloid-specific <em>Orai1</em> deficient mice was generated by crossing a LysM-Cre mouse line with <em>Orai1</em><sup><em>f/f</em></sup> mice. Bone marrow-derived macrophages (BMDMs) were isolated, cultured, and stimulated to induce M1 or M2 macrophage polarization. Intracellular Ca<sup>2+</sup> signals were measured by time-lapse confocal microscope imaging, with a Ca<sup>2+</sup> indicator (Fluo 4). Experimental AP was induced by hourly intraperitoneal injections of caerulein or retrograde biliopancreatic infusion of sodium taurocholate. Pancreatic tissue damage was assessed by histopathological scoring and immunostaining. Sepsis was induced by intraperitoneal injection of lipopolysaccharide; organ damage and serum pro-inflammatory cytokines were measured.</p></div><div><h3>Result</h3><p>Myeloid-specific <em>Orai1</em> deletion exhibited minimal effect on SOCE in M0 macrophages and promoted M2 macrophage polarization <em>ex vivo</em>. Myeloid-specific <em>Orai1</em> deletion did not affect pancreatic tissue damage, nor neutrophil or macrophage infiltration in two models of AP. Similarly, myeloid-specific <em>Orai1</em> deletion did not influence overall survival rate in a model of sepsis, nor lung, kidney, and liver damage; while serum pro-inflammatory cytokines, including IL-6, TNF-α, and IL-1β were higher in <em>Orai1</em><sup><em>ΔLysM</em></sup> mice, but were largely reduced in mice with Orai1 inhibitor.</p></div><div><h3>Conclusion</h3><p>Our data suggest that ORAI1 may not be a predominant SOCE channel in macrophages and play a limited role in mediating pancreatic tissue damage in AP.</p></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140802828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.pan.2024.05.529
Yongzheng Li , Zhiyao Fan , Yufan Meng , Jian Yang , Peilong Li , Shujie Liu , Chaoyu Pang , Lutao Du , Yunshan Wang , Hanxiang Zhan
Background
Pancreatic ductal adenocarcinoma (PDAC) is the digestive malignancy with poor prognosis, and there is still a lack of effective diagnostic biomarkers.
Objective
We aimed to explore the diagnostic efficiency of DNA methylation in peripheral blood monocytes (PBMCs) in PDAC.
Methods
850K BeadChips were used to detect genome-wide methylation of PBMCs. For the selected sites, MethylTarget assays was used for further verification. The support vector machine was used to establish the combined panel.
Results
A total of 167 PDAC patients and 113 healthy controls were included in this study and were divided into three sets. In the discovery set, we found 4625 differentially methylated positions (DMPs) between cancer group and healthy controls. ZFHX3 (0.16 ± 0.04 vs. 0.18 ± 0.04, P = 0.001), cg01904886 (0.84 ± 0.05 vs. 0.81 ± 0.04, P = 0.02) and NUMBL (0.96 ± 0.005 vs. 0.957 ± 0.005, P = 0.04) were found to be significantly different in training set. The locus with more significant differences, namely ZFHX3, was used for further validation and to establish a combined diagnostic panel with CA19-9. In the validation set, the ROC curve indicated that the AUC value of ZFHX3 was 0.75. The AUC value of the combined model (AUC = 0.92) was higher than that of CA19-9 alone (AUC = 0.88). In patients with normal CA19-9 levels, the ZFHX3 methylation biomarker still maintained good diagnostic efficacy (AUC = 0.71).
Conclusion
Our study preliminarily suggests that ZFHX3 methylation combined with CA19-9 can improve the detection rate of PDAC. Especially in patients with normal CA19-9, ZFHX3 methylation can maintain stable diagnostic efficacy. The diagnostic value of ZFHX3 methylation still needs to be prospectively validated.
{"title":"ZFHX3 methylation in peripheral blood monocytes as a potential biomarker for pancreatic cancer detection","authors":"Yongzheng Li , Zhiyao Fan , Yufan Meng , Jian Yang , Peilong Li , Shujie Liu , Chaoyu Pang , Lutao Du , Yunshan Wang , Hanxiang Zhan","doi":"10.1016/j.pan.2024.05.529","DOIUrl":"10.1016/j.pan.2024.05.529","url":null,"abstract":"<div><h3>Background</h3><p>Pancreatic ductal adenocarcinoma (PDAC) is the digestive malignancy with poor prognosis, and there is still a lack of effective diagnostic biomarkers.</p></div><div><h3>Objective</h3><p>We aimed to explore the diagnostic efficiency of DNA methylation in peripheral blood monocytes (PBMCs) in PDAC.</p></div><div><h3>Methods</h3><p>850K BeadChips were used to detect genome-wide methylation of PBMCs. For the selected sites, MethylTarget assays was used for further verification. The support vector machine was used to establish the combined panel.</p></div><div><h3>Results</h3><p>A total of 167 PDAC patients and 113 healthy controls were included in this study and were divided into three sets. In the discovery set, we found 4625 differentially methylated positions (DMPs) between cancer group and healthy controls. ZFHX3 (0.16 ± 0.04 vs. 0.18 ± 0.04, P = 0.001), cg01904886 (0.84 ± 0.05 vs. 0.81 ± 0.04, P = 0.02) and NUMBL (0.96 ± 0.005 vs. 0.957 ± 0.005, P = 0.04) were found to be significantly different in training set. The locus with more significant differences, namely ZFHX3, was used for further validation and to establish a combined diagnostic panel with CA19-9. In the validation set, the ROC curve indicated that the AUC value of ZFHX3 was 0.75. The AUC value of the combined model (AUC = 0.92) was higher than that of CA19-9 alone (AUC = 0.88). In patients with normal CA19-9 levels, the ZFHX3 methylation biomarker still maintained good diagnostic efficacy (AUC = 0.71).</p></div><div><h3>Conclusion</h3><p>Our study preliminarily suggests that ZFHX3 methylation combined with CA19-9 can improve the detection rate of PDAC. Especially in patients with normal CA19-9, ZFHX3 methylation can maintain stable diagnostic efficacy. The diagnostic value of ZFHX3 methylation still needs to be prospectively validated.</p></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141280500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.pan.2024.04.005
Bo-Hyung Kim , Minji Kwon , Donghwan Lee , Se Woo Park , Eun Shin
Objectives
We aimed to assess the diagnostic utility of an immunohistochemical panel including calcium-binding protein P, p53, Ki-67, and SMAD family member 4 and K-ras mutation for diagnosing pancreatic solid lesion specimens obtained by endoscopic ultrasound-guided fine-needle biopsy and to confirm their usefulness in histologically inconclusive cases.
Methods
Immunohistochemistry and peptide nucleic acid-clamping polymerase chain reaction for K-ras mutation were performed on 96 endoscopic ultrasound-guided fine-needle biopsy specimens. The diagnostic efficacy of each marker and the combination of markers was calculated. The diagnostic performances of these markers were evaluated in 27 endoscopic ultrasound-guided fine-needle biopsy specimens with histologically inconclusive diagnoses. A classification tree was constructed.
Results
K-ras mutation showed the highest accuracy and consistency. Positivity in more than two or three of the five markers showed high diagnostic accuracy (94.6 % and 93.6 %, respectively), and positivity for more than three markers showed the highest accuracy for inconclusive cases (92.0 %). A classification tree using K-ras mutation, Ki-67, S100P, and SMAD4 showed high diagnostic performance, with only two misclassifications in inconclusive cases.
Conclusions
K-ras mutation detection via peptide nucleic acid-clamping polymerase chain reaction is a stable and accurate method for distinguishing between pancreatic ductal adenocarcinoma and non-pancreatic ductal adenocarcinoma lesions. A classification tree using K-ras mutation, Ki-67, S100P, and SMAD4 helps increase the diagnostic accuracy of cases that are histologically difficult to diagnose.
{"title":"K-ras mutation detected by peptide nucleic acid-clamping polymerase chain reaction, Ki-67, S100P, and SMAD4 expression can improve the diagnostic accuracy of inconclusive pancreatic EUS-FNB specimens","authors":"Bo-Hyung Kim , Minji Kwon , Donghwan Lee , Se Woo Park , Eun Shin","doi":"10.1016/j.pan.2024.04.005","DOIUrl":"10.1016/j.pan.2024.04.005","url":null,"abstract":"<div><h3>Objectives</h3><p>We aimed to assess the diagnostic utility of an immunohistochemical panel including calcium-binding protein P, p53, Ki-67, and SMAD family member 4 and <em>K-ras</em> mutation for diagnosing pancreatic solid lesion specimens obtained by endoscopic ultrasound-guided fine-needle biopsy and to confirm their usefulness in histologically inconclusive cases.</p></div><div><h3>Methods</h3><p>Immunohistochemistry and peptide nucleic acid-clamping polymerase chain reaction for <em>K-ras</em> mutation were performed on 96 endoscopic ultrasound-guided fine-needle biopsy specimens. The diagnostic efficacy of each marker and the combination of markers was calculated. The diagnostic performances of these markers were evaluated in 27 endoscopic ultrasound-guided fine-needle biopsy specimens with histologically inconclusive diagnoses. A classification tree was constructed.</p></div><div><h3>Results</h3><p><em>K-ras</em> mutation showed the highest accuracy and consistency. Positivity in more than two or three of the five markers showed high diagnostic accuracy (94.6 % and 93.6 %, respectively), and positivity for more than three markers showed the highest accuracy for inconclusive cases (92.0 %). A classification tree using <em>K-ras</em> mutation, Ki-67, S100P, and SMAD4 showed high diagnostic performance, with only two misclassifications in inconclusive cases.</p></div><div><h3>Conclusions</h3><p><em>K-ras</em> mutation detection via peptide nucleic acid-clamping polymerase chain reaction is a stable and accurate method for distinguishing between pancreatic ductal adenocarcinoma and non-pancreatic ductal adenocarcinoma lesions. A classification tree using <em>K-ras</em> mutation, Ki-67, S100P, and SMAD4 helps increase the diagnostic accuracy of cases that are histologically difficult to diagnose.</p></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140765288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.pan.2024.05.515
Isha Singh , Joanne F. Chou , Marinela Capanu , Jennifer Park , Kenneth H. Yu , Anna M. Varghese , Wungki Park , Alice Zervoudakis , Fergus Keane , Vineet Syan Rolston , Hans Gerdes , Alice C. Wei , Pari Shah , Anne Covey , Mark Schattner , Eileen M. O'Reilly
Background
Acute cholangitis (AC) is a common complication of pancreatic ductal adenocarcinoma (PDAC). Herein, we evaluated outcomes after the first AC episode and predictors of mortality and AC recurrence in patients with stage IV PDAC.
Methods
We conducted a single-center, retrospective observational study using institutional databases. Clinical data and outcomes for patients with stage IV PDAC and at least one documented episode of AC, were assessed. Overall survival (OS) was estimated using the Kaplan-Meier method, and Cox regression model was employed to identify predictors of AC recurrence and mortality.
Results
One hundred and twenty-four patients with stage IV PDAC and AC identified between January 01, 2014 and October 31, 2020 were included. Median OS after first episode of AC was 4.1 months (95 % CI, 4.0–5.5), and 30-day, 6, and 12-month survival was 86.2 % (95 % CI, 80.3–92.5), 37 % (95 % CI, 29.3–46.6 %) and 18.9 % (95 % CI, 13.1–27.3 %), respectively. Primary tumor in pancreatic body/tail (HR 2.29, 95 % CI: 1.26 to 4.18, p = 0.011), concomitant metastases to liver and other sites (HR 1.96, 95 % CI: 1.16 to 3.31, p = 0.003) and grade 3 AC (HR 2.26, 95 % CI: 1.45 to 3.52, p < 0.001), predicted worse outcomes. Intensive care unit admission, sepsis, systemic therapy, treatment regimen, and time to intervention did not predict survival or risk of recurrence of AC.
Conclusions
AC confers significant morbidity and mortality in advanced PDAC. Worse outcomes are associated with higher grade AC, primary tumor location in pancreatic body/tail, and metastases to liver and other sites.
{"title":"Morbidity and mortality in patients with stage IV pancreatic adenocarcinoma and acute cholangitis: Outcomes and risk prognostication","authors":"Isha Singh , Joanne F. Chou , Marinela Capanu , Jennifer Park , Kenneth H. Yu , Anna M. Varghese , Wungki Park , Alice Zervoudakis , Fergus Keane , Vineet Syan Rolston , Hans Gerdes , Alice C. Wei , Pari Shah , Anne Covey , Mark Schattner , Eileen M. O'Reilly","doi":"10.1016/j.pan.2024.05.515","DOIUrl":"10.1016/j.pan.2024.05.515","url":null,"abstract":"<div><h3>Background</h3><p>Acute cholangitis (AC) is a common complication of pancreatic ductal adenocarcinoma (PDAC). Herein, we evaluated outcomes after the first AC episode and predictors of mortality and AC recurrence in patients with stage IV PDAC.</p></div><div><h3>Methods</h3><p>We conducted a single-center, retrospective observational study using institutional databases. Clinical data and outcomes for patients with stage IV PDAC and at least one documented episode of AC, were assessed. Overall survival (OS) was estimated using the Kaplan-Meier method, and Cox regression model was employed to identify predictors of AC recurrence and mortality.</p></div><div><h3>Results</h3><p>One hundred and twenty-four patients with stage IV PDAC and AC identified between January 01, 2014 and October 31, 2020 were included. Median OS after first episode of AC was 4.1 months (95 % CI, 4.0–5.5), and 30-day, 6, and 12-month survival was 86.2 % (95 % CI, 80.3–92.5), 37 % (95 % CI, 29.3–46.6 %) and 18.9 % (95 % CI, 13.1–27.3 %), respectively. Primary tumor in pancreatic body/tail (HR 2.29, 95 % CI: 1.26 to 4.18, p = 0.011), concomitant metastases to liver and other sites (HR 1.96, 95 % CI: 1.16 to 3.31, p = 0.003) and grade 3 AC (HR 2.26, 95 % CI: 1.45 to 3.52, p < 0.001), predicted worse outcomes. Intensive care unit admission, sepsis, systemic therapy, treatment regimen, and time to intervention did not predict survival or risk of recurrence of AC.</p></div><div><h3>Conclusions</h3><p>AC confers significant morbidity and mortality in advanced PDAC. Worse outcomes are associated with higher grade AC, primary tumor location in pancreatic body/tail, and metastases to liver and other sites.</p></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1424390324006240/pdfft?md5=812e343a10312f2baa57e2efdbd78298&pid=1-s2.0-S1424390324006240-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140928996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.pan.2024.04.006
Nicolò de Pretis , Luigi Martinelli , Enrico Palmeri , Federico Caldart , Salvatore Crucillà , Alberto Zorzi , Alessandro Brillo , Stefano Francesco Crinò , Maria Cristina Conti Bellocchi , Laura Bernardoni , Giulia De Marchi , Antonio Amodio , Pietro Campagnola , Rachele Ciccocioppo , Armando Gabbrielli , Alessandro Marcon , Luca Frulloni
Background/objectives
Autoimmune pancreatitis (AIP) is a steroid-responsive inflammatory disease of the pancreas. Few studies investigated pancreatic exocrine function (PEF) in patients suffering from AIP and no definitive data are available on the effect of steroids in PEF recovery. Aim of the study is the evaluation of severe pancreatic insufficiency (sPEI) prevalence in AIP at clinical onset and after steroid treatment.
Methods
312 Patients with diagnosis of AIP between January 1st, 2010 and December 31st, 2020 were identified in our prospectively maintained register. Patients with a pre-steroid treatment dosage of fecal elastase-1 (FE-1) were included. Changes in PEF were evaluated in patients with available pre- and post-treatment FE (between 3 and 12 months after steroid).
Results
One-hundred-twenty-four patients were included, with a median FE-1 of 122 (Q1-Q3: 15–379) μg/g at baseline. Fifty-nine (47.6 %) had sPEI (FE-1<100 μg/g). Univariable analysis identified type 1 AIP, radiological involvement of the head of the pancreas (diffuse involvement of the pancreas or focal involvement of the head), weight loss, age and diabetes as associated with a greater risk of sPEI. However, at multivariable analysis, only the involvement of the head of the pancreas was identified as independent risk factor for sPEI. After steroids, mean FE-1 changed from 64 (15–340) to 202 (40–387) μg/g (P = 0.058) and head involvement was the only predictor of improvement of sPEI.
Conclusion
The inflammatory involvement of the head of the pancreas is associated with PEF severity, as well as PEF improvement after treatment with steroids in patients with AIP.
{"title":"The effect of steroid therapy on pancreatic exocrine function in autoimmune pancreatitis","authors":"Nicolò de Pretis , Luigi Martinelli , Enrico Palmeri , Federico Caldart , Salvatore Crucillà , Alberto Zorzi , Alessandro Brillo , Stefano Francesco Crinò , Maria Cristina Conti Bellocchi , Laura Bernardoni , Giulia De Marchi , Antonio Amodio , Pietro Campagnola , Rachele Ciccocioppo , Armando Gabbrielli , Alessandro Marcon , Luca Frulloni","doi":"10.1016/j.pan.2024.04.006","DOIUrl":"10.1016/j.pan.2024.04.006","url":null,"abstract":"<div><h3>Background/objectives</h3><p>Autoimmune pancreatitis (AIP) is a steroid-responsive inflammatory disease of the pancreas. Few studies investigated pancreatic exocrine function (PEF) in patients suffering from AIP and no definitive data are available on the effect of steroids in PEF recovery. Aim of the study is the evaluation of severe pancreatic insufficiency (sPEI) prevalence in AIP at clinical onset and after steroid treatment.</p></div><div><h3>Methods</h3><p>312 Patients with diagnosis of AIP between January 1st<sup>,</sup> 2010 and December 31st<sup>,</sup> 2020 were identified in our prospectively maintained register. Patients with a pre-steroid treatment dosage of fecal elastase-1 (FE-1) were included. Changes in PEF were evaluated in patients with available pre- and post-treatment FE (between 3 and 12 months after steroid).</p></div><div><h3>Results</h3><p>One-hundred-twenty-four patients were included, with a median FE-1 of 122 (Q1-Q3: 15–379) μg/g at baseline. Fifty-nine (47.6 %) had sPEI (FE-1<100 μg/g). Univariable analysis identified type 1 AIP, radiological involvement of the head of the pancreas (diffuse involvement of the pancreas or focal involvement of the head), weight loss, age and diabetes as associated with a greater risk of sPEI. However, at multivariable analysis, only the involvement of the head of the pancreas was identified as independent risk factor for sPEI. After steroids, mean FE-1 changed from 64 (15–340) to 202 (40–387) μg/g (P = 0.058) and head involvement was the only predictor of improvement of sPEI.</p></div><div><h3>Conclusion</h3><p>The inflammatory involvement of the head of the pancreas is associated with PEF severity, as well as PEF improvement after treatment with steroids in patients with AIP.</p></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1424390324001078/pdfft?md5=db61988d712da19c70be02863fab0255&pid=1-s2.0-S1424390324001078-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140787943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.pan.2024.03.010
Jan Stanisław Bukowski, Jan Jankowski, Daniel Bałut, Sławomir Kozieł, Jan Pertkiewicz, Aleksandra Banaszkiewicz
{"title":"Ansa pancreatica as a rare cause of pancreatitis: A review of case reports","authors":"Jan Stanisław Bukowski, Jan Jankowski, Daniel Bałut, Sławomir Kozieł, Jan Pertkiewicz, Aleksandra Banaszkiewicz","doi":"10.1016/j.pan.2024.03.010","DOIUrl":"10.1016/j.pan.2024.03.010","url":null,"abstract":"","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140166493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.pan.2024.04.003
Mohamed O. Othman , Christopher Forsmark , Dhiraj Yadav , Vikesh K. Singh , Luis F. Lara , Walter Park , Zuoyi Zhang , Jun Yu , Jens J. Kort
Background/Objectives
No simple, accurate diagnostic tests exist for exocrine pancreatic insufficiency (EPI), and EPI remains underdiagnosed in chronic pancreatitis (CP). We sought to develop a digital screening tool to assist clinicians to predict EPI in patients with definite CP.
Methods
This was a retrospective case-control study of patients with definite CP with/without EPI. Overall, 49 candidate predictor variables were utilized to train a Classification and Regression Tree (CART) model to rank all predictors and select a parsimonious set of predictors for EPI status. Five-fold cross-validation was used to assess generalizability, and the full CART model was compared with 4 additional predictive models. EPI misclassification rate (mRate) served as primary endpoint metric.
Results
274 patients with definite CP from 6 pancreatitis centers across the United States were included, of which 58 % had EPI based on predetermined criteria. The optimal CART decision tree included 10 variables. The mRate without/with 5-fold cross-validation of the CART was 0.153 (training error) and 0.314 (prediction error), and the area under the receiver operating characteristic curve was 0.889 and 0.682, respectively. Sensitivity and specificity without/with 5-fold cross-validation was 0.888/0.789 and 0.794/0.535, respectively. A trained second CART without pancreas imaging variables (n = 6), yielded 8 variables. Training error/prediction error was 0.190/0.351; sensitivity was 0.869/0.650, and specificity was 0.728/0.649, each without/with 5-fold cross-validation.
Conclusion
We developed two CART models that were integrated into one digital screening tool to assess for EPI in patients with definite CP and with two to six input variables needed for predicting EPI status.
{"title":"Development of clinical screening tool for exocrine pancreatic insufficiency in patients with definite chronic pancreatitis","authors":"Mohamed O. Othman , Christopher Forsmark , Dhiraj Yadav , Vikesh K. Singh , Luis F. Lara , Walter Park , Zuoyi Zhang , Jun Yu , Jens J. Kort","doi":"10.1016/j.pan.2024.04.003","DOIUrl":"10.1016/j.pan.2024.04.003","url":null,"abstract":"<div><h3>Background/Objectives</h3><p>No simple, accurate diagnostic tests exist for exocrine pancreatic insufficiency (EPI), and EPI remains underdiagnosed in chronic pancreatitis (CP). We sought to develop a digital screening tool to assist clinicians to predict EPI in patients with definite CP.</p></div><div><h3>Methods</h3><p>This was a retrospective case-control study of patients with definite CP with/without EPI. Overall, 49 candidate predictor variables were utilized to train a Classification and Regression Tree (CART) model to rank all predictors and select a parsimonious set of predictors for EPI status. Five-fold cross-validation was used to assess generalizability, and the full CART model was compared with 4 additional predictive models. EPI misclassification rate (mRate) served as primary endpoint metric.</p></div><div><h3>Results</h3><p>274 patients with definite CP from 6 pancreatitis centers across the United States were included, of which 58 % had EPI based on predetermined criteria. The optimal CART decision tree included 10 variables. The mRate without/with 5-fold cross-validation of the CART was 0.153 (training error) and 0.314 (prediction error), and the area under the receiver operating characteristic curve was 0.889 and 0.682, respectively. Sensitivity and specificity without/with 5-fold cross-validation was 0.888/0.789 and 0.794/0.535, respectively. A trained second CART without pancreas imaging variables (n = 6), yielded 8 variables. Training error/prediction error was 0.190/0.351; sensitivity was 0.869/0.650, and specificity was 0.728/0.649, each without/with 5-fold cross-validation.</p></div><div><h3>Conclusion</h3><p>We developed two CART models that were integrated into one digital screening tool to assess for EPI in patients with definite CP and with two to six input variables needed for predicting EPI status.</p></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1424390324001029/pdfft?md5=81381c9ea1d95b9033cbe9572387cf22&pid=1-s2.0-S1424390324001029-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140766533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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