Pub Date : 2025-03-08DOI: 10.1016/j.pan.2025.03.003
Rujuan Liu, Kui Wang, Li Wen
{"title":"Author's reply to the letter to editor regarding \"A causal relationship between distinct immune features and acute or chronic pancreatitis: Results from a Mendelian Randomization analysis\".","authors":"Rujuan Liu, Kui Wang, Li Wen","doi":"10.1016/j.pan.2025.03.003","DOIUrl":"https://doi.org/10.1016/j.pan.2025.03.003","url":null,"abstract":"","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625504","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 : 2025-03-04DOI: 10.1016/j.pan.2025.03.001
Rasmus Hagn-Meincke, Jens Brøndum Frøkjær, Asbjørn Mohr Drewes, Charlotte Henneberg Holmboe, Klaus Krogh, Rasmus Bach Nedergaard, Line Davidsen, Tina Okdahl, Ingfrid Salvesen Haldorsen, Walter Park, Bent Winding Deleuran, Søren Schou Olesen
Background: Chronic pancreatitis (CP) is a fibro-inflammatory disease that damages the pancreas, leading to severe abdominal pain and metabolic complications. Activated macrophages and pancreatic stellate cells drive CP progression, and their activity is regulated by complex immune signals, including interleukin-6 (IL-6). Preclinical studies suggest that blocking IL-6 signalling may have pain-relieving effects in CP. Based on these findings, we hypothesise that tocilizumab, an anti-IL-6 receptor antibody, will reduce abdominal pain and improve physical functioning and quality of life in patients with CP. Additionally, we expect tocilizumab to decrease pancreatic inflammation, fibrosis, and systemic inflammation, as well as normalise pain processing.
Methods: The TOPAC trial is a phase 2, randomised, placebo-controlled, double-blinded, investigator-initiated trial conducted at Aalborg University Hospital, Denmark. Patients with painful CP and suspicion of sustained pancreatic inflammation (n = 36) will be randomised (1:1) to receive intravenous tocilizumab (8 mg/kg) or a corresponding placebo every 4 weeks for 24 weeks. The primary endpoint is the difference between the two groups in the change of the Comprehensive Pain Assessment Tool Short Form (COMPAT-SF) score from baseline to 24 weeks. Secondary outcomes include questionnaires focused on quality of life, physical/daily functioning, and the severity of pain and its impact on functioning. Additionally, safety is a key secondary endpoint. Exploratory outcomes include soluble biomarkers of inflammation and fibrosis, multiparametric pancreatic magnetic resonance imaging, quantitative sensory testing and neurophysiological measurements of the pain processing.
Conclusions: This placebo-controlled clinical trial aims to study the potential clinical benefits of blocking IL-6 signalling in painful CP.
{"title":"Tocilizumab for Painful Chronic Pancreatitis (TOPAC trial): Protocol for a phase 2 randomized, placebo-controlled, double-blind, investigator-initiated trial.","authors":"Rasmus Hagn-Meincke, Jens Brøndum Frøkjær, Asbjørn Mohr Drewes, Charlotte Henneberg Holmboe, Klaus Krogh, Rasmus Bach Nedergaard, Line Davidsen, Tina Okdahl, Ingfrid Salvesen Haldorsen, Walter Park, Bent Winding Deleuran, Søren Schou Olesen","doi":"10.1016/j.pan.2025.03.001","DOIUrl":"https://doi.org/10.1016/j.pan.2025.03.001","url":null,"abstract":"<p><strong>Background: </strong>Chronic pancreatitis (CP) is a fibro-inflammatory disease that damages the pancreas, leading to severe abdominal pain and metabolic complications. Activated macrophages and pancreatic stellate cells drive CP progression, and their activity is regulated by complex immune signals, including interleukin-6 (IL-6). Preclinical studies suggest that blocking IL-6 signalling may have pain-relieving effects in CP. Based on these findings, we hypothesise that tocilizumab, an anti-IL-6 receptor antibody, will reduce abdominal pain and improve physical functioning and quality of life in patients with CP. Additionally, we expect tocilizumab to decrease pancreatic inflammation, fibrosis, and systemic inflammation, as well as normalise pain processing.</p><p><strong>Methods: </strong>The TOPAC trial is a phase 2, randomised, placebo-controlled, double-blinded, investigator-initiated trial conducted at Aalborg University Hospital, Denmark. Patients with painful CP and suspicion of sustained pancreatic inflammation (n = 36) will be randomised (1:1) to receive intravenous tocilizumab (8 mg/kg) or a corresponding placebo every 4 weeks for 24 weeks. The primary endpoint is the difference between the two groups in the change of the Comprehensive Pain Assessment Tool Short Form (COMPAT-SF) score from baseline to 24 weeks. Secondary outcomes include questionnaires focused on quality of life, physical/daily functioning, and the severity of pain and its impact on functioning. Additionally, safety is a key secondary endpoint. Exploratory outcomes include soluble biomarkers of inflammation and fibrosis, multiparametric pancreatic magnetic resonance imaging, quantitative sensory testing and neurophysiological measurements of the pain processing.</p><p><strong>Conclusions: </strong>This placebo-controlled clinical trial aims to study the potential clinical benefits of blocking IL-6 signalling in painful CP.</p>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605978","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}
Background: The aim of this study was to elucidate the association of pancreatic fluid cytology with intrapancreatic recurrence of intraductal papillary mucinous neoplasms (IPMNs).
Materials and methods: A total of 68 patients with IPMN who underwent pancreatectomy and obtained cytologic analysis of pancreatic fluid at Jichi Medical University Hospital were included in this study. Computed tomography scan and magnetic resonance cholangiopancreatography were performed preoperatively. Endoscopic retrograde cholangiopancreatography was used to obtain pancreatic fluid. The association of recurrence with variables was determined by logistic regression multivariate analysis.
Results: Class V cytology was found in 7/68 patients preoperatively. Metachronous intrapancreatic recurrences occurred in 6/68 patients, including one branched type, main pancreatic duct type in two and mixed pancreatic duct type in three. Four of seven patients with class V cytology developed intra-pancreatic recurrences as a new lesion. Class V cytology was significantly associated with intrapancreatic recurrence, compared to those with class IV or lower cytology. In univariate analysis, patients with pathological findings with high-grade dysplasia or adenocarcinoma (P = 0.0392, odds ratio (OR) 10.2, 95 % confidence interval (CI) 1.12-93.6) and class V pancreatic fluid cytology (P = 0.0005, OR 38.7, 95 % CI 4.94-302) were significant risk factors. In multivariate analysis, class V pancreatic fluid cytology was significantly associated with developing intrapancreatic recurrence (P = 0.0149, OR 22.7, 95 % CI 1.83-279).
Conclusion: Preoperative class V pancreatic fluid cytology is associated with intra-pancreatic recurrence after resection of IPMN.
{"title":"Class V pancreatic fluid cytology is associated with intrapancreatic recurrence of intraductal papillary mucinous neoplasms.","authors":"Takumi Saito, Atsushi Miki, Yasunaru Sakuma, Jun Watanabe, Hideki Sasanuma, Takumi Teratani, Wataru Nishimura, Noriyoshi Fukushima, Joji Kitayama, Naohiro Sata, Hironori Yamaguchi","doi":"10.1016/j.pan.2025.03.002","DOIUrl":"https://doi.org/10.1016/j.pan.2025.03.002","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to elucidate the association of pancreatic fluid cytology with intrapancreatic recurrence of intraductal papillary mucinous neoplasms (IPMNs).</p><p><strong>Materials and methods: </strong>A total of 68 patients with IPMN who underwent pancreatectomy and obtained cytologic analysis of pancreatic fluid at Jichi Medical University Hospital were included in this study. Computed tomography scan and magnetic resonance cholangiopancreatography were performed preoperatively. Endoscopic retrograde cholangiopancreatography was used to obtain pancreatic fluid. The association of recurrence with variables was determined by logistic regression multivariate analysis.</p><p><strong>Results: </strong>Class V cytology was found in 7/68 patients preoperatively. Metachronous intrapancreatic recurrences occurred in 6/68 patients, including one branched type, main pancreatic duct type in two and mixed pancreatic duct type in three. Four of seven patients with class V cytology developed intra-pancreatic recurrences as a new lesion. Class V cytology was significantly associated with intrapancreatic recurrence, compared to those with class IV or lower cytology. In univariate analysis, patients with pathological findings with high-grade dysplasia or adenocarcinoma (P = 0.0392, odds ratio (OR) 10.2, 95 % confidence interval (CI) 1.12-93.6) and class V pancreatic fluid cytology (P = 0.0005, OR 38.7, 95 % CI 4.94-302) were significant risk factors. In multivariate analysis, class V pancreatic fluid cytology was significantly associated with developing intrapancreatic recurrence (P = 0.0149, OR 22.7, 95 % CI 1.83-279).</p><p><strong>Conclusion: </strong>Preoperative class V pancreatic fluid cytology is associated with intra-pancreatic recurrence after resection of IPMN.</p>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586648","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 : 2025-03-01DOI: 10.1016/j.pan.2024.11.015
Bojan Kovacevic , Caroline Ewertsen , Thomas Skårup Kristensen , Luit Penninga , Carsten Palnæs Hansen
Background
Surgery is the only curative treatment for pancreatic cancer, but less than 25 % of the patients present with a resectable tumor at the time of diagnosis. The aim of this study is to evaluate progression during surgical treatment delay and examine any associations between surgical treatment delay and survival.
Methods
This is a retrospective, single center propensity score matched study including treatment naïve patients with pancreatic adenocarcinoma between 2018 and 2022. Outcomes included disease progression during surgical treatment delay in patients where follow-up imaging was performed as well as overall and recurrence-free survival for the entire cohort.
Results
The study cohort consisted of 290 patients of whom 129 (44.5 %) underwent follow-up imaging. Radiological progression to unresectable disease during surgical delay was seen in 14 cases (10.9 %), with another 17 cases (13.2 %) deemed unresectable during intended resection. Tumor size progression was observed in 29 patients (22.5 %) with an average tumor growth rate of 7.4 mm (95%CI 5.8–8.9, p < 0.001). Median time to surgery was 37 days with no observed associations between treatment delay and overall survival (HR = 1.02, 95%CI 0.76–1.38, p = 0.996), or the risk of recurrence (HR = 1.06, 95%CI 0.77–1.48, p = 0.709).
Conclusion
Progression in tumor size does not seem to affect survival in our study population. In general, surgical treatment delay in up-front resectable patients does not seem to be associated with survival or the risk of recurrence, but the optimal and maximal time to surgery as well as the optimal timing of the follow-up scanning remain unclear.
背景：手术是治疗胰腺癌的唯一方法，但不到25%的患者在诊断时存在可切除的肿瘤。本研究的目的是评估手术治疗延迟期间的进展，并检查手术治疗延迟与生存之间的任何关联。方法：这是一项回顾性、单中心倾向评分匹配研究，包括2018年至2022年间治疗naïve胰腺腺癌患者。结果包括手术治疗延迟期间患者的疾病进展，随访影像学检查以及整个队列的总生存率和无复发生存率。结果：研究队列包括290例患者，其中129例（44.5%）接受了随访影像学检查。14例（10.9%）在手术延迟期间放射学进展为不可切除的疾病，另有17例（13.2%）在预定切除期间被认为不可切除。29例患者（22.5%）观察到肿瘤大小进展，平均肿瘤生长速度为7.4 mm （95%CI 5.8-8.9, p）。结论：肿瘤大小进展似乎不影响我们研究人群的生存。一般来说，可预先切除患者的手术治疗延迟似乎与生存或复发风险无关，但最佳和最大手术时间以及最佳随访扫描时间尚不清楚。
{"title":"Progression of resectable pancreatic ductal adenocarcinoma during surgical delay and effects on survival – A propensity score matched study","authors":"Bojan Kovacevic , Caroline Ewertsen , Thomas Skårup Kristensen , Luit Penninga , Carsten Palnæs Hansen","doi":"10.1016/j.pan.2024.11.015","DOIUrl":"10.1016/j.pan.2024.11.015","url":null,"abstract":"<div><h3>Background</h3><div>Surgery is the only curative treatment for pancreatic cancer, but less than 25 % of the patients present with a resectable tumor at the time of diagnosis. The aim of this study is to evaluate progression during surgical treatment delay and examine any associations between surgical treatment delay and survival.</div></div><div><h3>Methods</h3><div>This is a retrospective, single center propensity score matched study including treatment naïve patients with pancreatic adenocarcinoma between 2018 and 2022. Outcomes included disease progression during surgical treatment delay in patients where follow-up imaging was performed as well as overall and recurrence-free survival for the entire cohort.</div></div><div><h3>Results</h3><div>The study cohort consisted of 290 patients of whom 129 (44.5 %) underwent follow-up imaging. Radiological progression to unresectable disease during surgical delay was seen in 14 cases (10.9 %), with another 17 cases (13.2 %) deemed unresectable during intended resection. Tumor size progression was observed in 29 patients (22.5 %) with an average tumor growth rate of 7.4 mm (95%CI 5.8–8.9, p < 0.001). Median time to surgery was 37 days with no observed associations between treatment delay and overall survival (HR = 1.02, 95%CI 0.76–1.38, p = 0.996), or the risk of recurrence (HR = 1.06, 95%CI 0.77–1.48, p = 0.709).</div></div><div><h3>Conclusion</h3><div>Progression in tumor size does not seem to affect survival in our study population. In general, surgical treatment delay in up-front resectable patients does not seem to be associated with survival or the risk of recurrence, but the optimal and maximal time to surgery as well as the optimal timing of the follow-up scanning remain unclear.</div></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":"25 2","pages":"Pages 228-233"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771047","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}
Acute Pancreatitis (AP) is a formidable disease with significant morbidity, mortality and healthcare expenditure. There is an emergent need to develop therapeutic agents for this disease as there are no targeted therapies available. We have recently demonstrated that pirfenidone can significantly decrease the severity of AP in animal models. Based on our preclinical findings, we decided to conduct a pilot trial to evaluate the safety, tolerability and efficacy of pirfenidone in patients with AP.
Methods
We have designed a multicenter, randomized, pilot clinical trial of 60 patients with blinded outcome assessment. All patients with AP, who present within 48 h of establishment of the diagnosis, will be screened for exclusion and inclusion criteria. Consenting patients will be randomized into pirfenidone or placebo within 48 h of the diagnosis of AP. The primary end points include decrease in PAN-PROMISE score after 72 h of initiation of drug, reduction in inflammatory markers, and development of serious adverse events. The secondary end points include changes in PAN-PROMISE score, discharge PASS score <60, development of composite outcome of new or worsening necrotizing pancreatitis on CT scan performed 5–7 days after admission, major infection or death, and readmissions and/or ER visits within 30 days and within 6 months after discharge.
Status
Currently enrolling (NCT05350371).
Conclusion
There is an urgent need to identify novel therapies for AP. This pilot clinical trial may become the basis of a larger study to analyze the efficacy of pirfenidone in patients with AP.
{"title":"Safety, tolerability and therapeutic efficacy of anti-inflammatory drug pirfenidone in acute pancreatitis patients: Protocol for a randomized pilot clinical trial","authors":"Ejas P. Bava , Tejeshwar Jain , Mustafa Al-Obaidi , Zoe Evans , Dureti Doto , Santhi Swaroop Vege , Vikas Dudeja","doi":"10.1016/j.pan.2025.01.004","DOIUrl":"10.1016/j.pan.2025.01.004","url":null,"abstract":"<div><h3>Background</h3><div>Acute Pancreatitis (AP) is a formidable disease with significant morbidity, mortality and healthcare expenditure. There is an emergent need to develop therapeutic agents for this disease as there are no targeted therapies available. We have recently demonstrated that pirfenidone can significantly decrease the severity of AP in animal models. Based on our preclinical findings, we decided to conduct a pilot trial to evaluate the safety, tolerability and efficacy of pirfenidone in patients with AP.</div></div><div><h3>Methods</h3><div>We have designed a multicenter, randomized, pilot clinical trial of 60 patients with blinded outcome assessment. All patients with AP<strong>,</strong> who present within 48 h of establishment of the diagnosis, will be screened for exclusion and inclusion criteria. Consenting patients will be randomized into pirfenidone or placebo within 48 h of the diagnosis of AP. The primary end points include decrease in PAN-PROMISE score after 72 h of initiation of drug, reduction in inflammatory markers, and development of serious adverse events. The secondary end points include changes in PAN-PROMISE score, discharge PASS score <60, development of composite outcome of new or worsening necrotizing pancreatitis on CT scan performed 5–7 days after admission, major infection or death, and readmissions and/or ER visits within 30 days and within 6 months after discharge.</div></div><div><h3>Status</h3><div>Currently enrolling (NCT05350371).</div></div><div><h3>Conclusion</h3><div>There is an urgent need to identify novel therapies for AP. This pilot clinical trial may become the basis of a larger study to analyze the efficacy of pirfenidone in patients with AP.</div></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":"25 2","pages":"Pages 214-220"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047646","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}
We previously reported that focal pancreatic parenchymal atrophy (FPPA) indicates high-grade pancreatic intraepithelial neoplasia (HG-PanIN) or carcinoma in situ (CIS). Because HG-PanIN progresses into pancreatic ductal adenocarcinoma (PDAC), the relationship between FPPA and PDAC should be investigated.
Methods
We included 54 patients with PDAC, whose previous computed tomography or magnetic resonance imaging were reviewed. The existence, positional relationship between FPPA and PDAC, and time between FPPA recognition and PDAC diagnosis were all examined. Of the 54 patients, 28 underwent surgery. The remaining 26 patients were histopathologically diagnosed with PDAC using endoscopic ultrasonography-guided fine needle aspiration.
Results
Among the 54 patients included, 49 (83.3 %) had FPPA. The pancreatic head and body were the common sites of FPPA. In all patients with FPPA, PDAC developed near the FPPA, with an average distance of 7.93 mm between the edge of the FPPA and the center of the PDAC. The interval between FPPA recognition and PDAC diagnosis was 35.33 months, which was significantly shorter in the surgical group.
Conclusions
FPPA could be a precursor of PDAC and suggest the area at risk of PDAC.
{"title":"Focal pancreatic parenchymal atrophy could be a precursor of pancreatic cancer","authors":"Masataka Kikuyama , Jun Nakahodo , Kazuro Chiba , Goro Honda","doi":"10.1016/j.pan.2025.01.003","DOIUrl":"10.1016/j.pan.2025.01.003","url":null,"abstract":"<div><h3>Background/objectives</h3><div>We previously reported that focal pancreatic parenchymal atrophy (FPPA) indicates high-grade pancreatic intraepithelial neoplasia (HG-PanIN) or carcinoma in situ (CIS). Because HG-PanIN progresses into pancreatic ductal adenocarcinoma (PDAC), the relationship between FPPA and PDAC should be investigated.</div></div><div><h3>Methods</h3><div>We included 54 patients with PDAC, whose previous computed tomography or magnetic resonance imaging were reviewed. The existence, positional relationship between FPPA and PDAC, and time between FPPA recognition and PDAC diagnosis were all examined. Of the 54 patients, 28 underwent surgery. The remaining 26 patients were histopathologically diagnosed with PDAC using endoscopic ultrasonography-guided fine needle aspiration.</div></div><div><h3>Results</h3><div>Among the 54 patients included, 49 (83.3 %) had FPPA. The pancreatic head and body were the common sites of FPPA. In all patients with FPPA, PDAC developed near the FPPA, with an average distance of 7.93 mm between the edge of the FPPA and the center of the PDAC. The interval between FPPA recognition and PDAC diagnosis was 35.33 months, which was significantly shorter in the surgical group.</div></div><div><h3>Conclusions</h3><div>FPPA could be a precursor of PDAC and suggest the area at risk of PDAC.</div></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":"25 2","pages":"Pages 241-249"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080815","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}
For metastatic pancreatic ductal adenocarcinoma (mPDAC), there are no established third-line chemotherapy options. We examined the efficacy and safety of third-line chemotherapy in patients with mPDAC in real-world practice.
Methods
We retrospectively analyzed 257 patients with mPDAC and progressive disease after first-line treatment with gemcitabine-based regimens and second-line treatment with liposomal irinotecan plus 5-fluorouracil and leucovorin at five Taiwanese medical centers from 2018 to 2022. Treatment efficacy and toxicity were analyzed in 77 of 257 patients receiving third-line treatment subsequently. We performed univariate and multivariate analyses to identify prognostic factors for overall survival (OS) in patients receiving third-line treatment.
Results
Patients receiving third-line treatment had a median OS of 4.5 months (95 % confidence interval [CI], 3.6–5.4), compared to 1.6 months (95 % CI, 1.3–1.9) for those who did not. Independent poor prognostic factors for OS included the absence of previous pancreatectomy (adjusted hazard ratio [aHR] 3.03, 95 % CI, 1.30–7.14, P = 0.001), an ECOG score of ≥2 ((aHR 9.81, 95 % CI 4.34–22.1, P < 0.001), and progressive disease response during second-line treatment (aHR 1.90, 95 % CI 1.21–8.91, P = 0.020, P = 0.020). Median OS for patients with none, one, two, and three poor prognostic factors were 15.9 (95 % CI, 12.3–19.6), 7.0 (2.6–13.3), 4.4 (3.5–5.2), and 2.0 (1.7–2.2) months, respectively. 43 of 77 patients (56 %) experienced at least one grade 3 or 4 toxicity.
Conclusion
In real-world settings, patients with mPDAC receiving third-line chemotherapy may have a moderate survival advantage, although clinicians should carefully select patients owing to high incidence of grade 3/4 toxicities.
{"title":"The efficacy and safety profile of third-line treatment in patients with metastatic pancreatic adenocarcinoma","authors":"Chi-Chen Lan , Tai-Jan Chiu , Chia-Yen Hung , Kun-Yun Yeh , Chang-Hsien Lu , Yen-Yang Chen , Jen-Shi Chen , Yu-Shin Hung , Wen-Chi Chou","doi":"10.1016/j.pan.2025.01.012","DOIUrl":"10.1016/j.pan.2025.01.012","url":null,"abstract":"<div><h3>Background</h3><div>For metastatic pancreatic ductal adenocarcinoma (mPDAC), there are no established third-line chemotherapy options. We examined the efficacy and safety of third-line chemotherapy in patients with mPDAC in real-world practice.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 257 patients with mPDAC and progressive disease after first-line treatment with gemcitabine-based regimens and second-line treatment with liposomal irinotecan plus 5-fluorouracil and leucovorin at five Taiwanese medical centers from 2018 to 2022. Treatment efficacy and toxicity were analyzed in 77 of 257 patients receiving third-line treatment subsequently. We performed univariate and multivariate analyses to identify prognostic factors for overall survival (OS) in patients receiving third-line treatment.</div></div><div><h3>Results</h3><div>Patients receiving third-line treatment had a median OS of 4.5 months (95 % confidence interval [CI], 3.6–5.4), compared to 1.6 months (95 % CI, 1.3–1.9) for those who did not. Independent poor prognostic factors for OS included the absence of previous pancreatectomy (adjusted hazard ratio [aHR] 3.03, 95 % CI, 1.30–7.14, P = 0.001), an ECOG score of ≥2 ((aHR 9.81, 95 % CI 4.34–22.1, P < 0.001), and progressive disease response during second-line treatment (aHR 1.90, 95 % CI 1.21–8.91, P = 0.020, P = 0.020). Median OS for patients with none, one, two, and three poor prognostic factors were 15.9 (95 % CI, 12.3–19.6), 7.0 (2.6–13.3), 4.4 (3.5–5.2), and 2.0 (1.7–2.2) months, respectively. 43 of 77 patients (56 %) experienced at least one grade 3 or 4 toxicity.</div></div><div><h3>Conclusion</h3><div>In real-world settings, patients with mPDAC receiving third-line chemotherapy may have a moderate survival advantage, although clinicians should carefully select patients owing to high incidence of grade 3/4 toxicities.</div></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":"25 2","pages":"Pages 266-274"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364829","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 : 2025-03-01DOI: 10.1016/j.pan.2024.12.015
Yvonne L. Eaglehouse , Sarah Darmon , Amie B. Park , Craig D. Shriver , Kangmin Zhu
Background
Pancreatic cancer has a high case fatality and treatment is known to improve survival. It is unknown whether the time between diagnosis and treatment initiation (time-to-treatment) is related to survival. Access to medical care may influence both treatment receipt and timing. We examined the relationship between time-to-treatment and survival among patients with pancreatic adenocarcinoma treated in the equal access Military Health System.
Methods
We used the MilCanEpi database to study a cohort of 806 men and women who were diagnosed with stage I-IV pancreatic adenocarcinoma between 1998 and 2014 and received either surgery or chemotherapy as primary treatment. Time-to-treatment in relation to overall survival was examined in multivariable time-dependent Cox regression models.
Results
Overall, median time-to-treatment was 3 weeks and 95 % of patients received treatment within 12 weeks. Time-to-treatment >6 weeks was associated with a statistically significant lower risk of death (AHR = 0.77, 95 % CI = 0.61–0.98) compared to time-to-treatment <3 weeks. Analysis by the first treatment type showed that time-to-surgery was not associated with survival among those receiving upfront surgery. Time-to-chemotherapy of >6 weeks was associated with reduced risks of death compared to <3 weeks (AHR = 0.62, 95 % CI = 0.48–0.80) for patients receiving primary chemotherapy.
Conclusions
Our data suggests that longer time-to-treatment, especially among patients with chemotherapy, was associated with lower risk of death among patients with pancreatic adenocarcinoma who received treatment. Further research is needed to understand the association of intervals along the whole cancer spectrum (e.g., presentation, diagnosis, treatment) and longer treatment intervals (i.e., >12 weeks) with survival.
背景：胰腺癌病死率高，治疗可提高生存率。目前尚不清楚诊断和开始治疗之间的时间（治疗时间）是否与生存有关。获得医疗保健可能会影响治疗的接受和时机。我们研究了在平等机会的军事卫生系统中接受治疗的胰腺腺癌患者的治疗时间与生存之间的关系。方法：我们使用MilCanEpi数据库对1998年至2014年间诊断为I-IV期胰腺腺癌并接受手术或化疗作为主要治疗的806名男性和女性进行队列研究。在多变量时间相关的Cox回归模型中检验了治疗时间与总生存率的关系。结果：总体而言，中位治疗时间为3周，95%的患者在12周内接受治疗。与接受治疗6周相比，接受治疗6周与死亡风险降低相关（AHR = 0.77, 95% CI = 0.61-0.98）。结论：我们的数据表明，接受治疗的胰腺腺癌患者，特别是接受化疗的患者，较长的治疗时间与较低的死亡风险相关。需要进一步的研究来了解整个癌症谱系的间隔（例如，表现，诊断，治疗）和较长的治疗间隔（例如，100 - 12周）与生存的关系。
{"title":"Time between pancreatic cancer diagnosis and treatment initiation and survival in the U.S. Military Health System","authors":"Yvonne L. Eaglehouse , Sarah Darmon , Amie B. Park , Craig D. Shriver , Kangmin Zhu","doi":"10.1016/j.pan.2024.12.015","DOIUrl":"10.1016/j.pan.2024.12.015","url":null,"abstract":"<div><h3>Background</h3><div>Pancreatic cancer has a high case fatality and treatment is known to improve survival. It is unknown whether the time between diagnosis and treatment initiation (time-to-treatment) is related to survival. Access to medical care may influence both treatment receipt and timing. We examined the relationship between time-to-treatment and survival among patients with pancreatic adenocarcinoma treated in the equal access Military Health System.</div></div><div><h3>Methods</h3><div>We used the MilCanEpi database to study a cohort of 806 men and women who were diagnosed with stage I-IV pancreatic adenocarcinoma between 1998 and 2014 and received either surgery or chemotherapy as primary treatment. Time-to-treatment in relation to overall survival was examined in multivariable time-dependent Cox regression models.</div></div><div><h3>Results</h3><div>Overall, median time-to-treatment was 3 weeks and 95 % of patients received treatment within 12 weeks. Time-to-treatment >6 weeks was associated with a statistically significant lower risk of death (AHR = 0.77, 95 % CI = 0.61–0.98) compared to time-to-treatment <3 weeks. Analysis by the first treatment type showed that time-to-surgery was not associated with survival among those receiving upfront surgery. Time-to-chemotherapy of >6 weeks was associated with reduced risks of death compared to <3 weeks (AHR = 0.62, 95 % CI = 0.48–0.80) for patients receiving primary chemotherapy.</div></div><div><h3>Conclusions</h3><div>Our data suggests that longer time-to-treatment, especially among patients with chemotherapy, was associated with lower risk of death among patients with pancreatic adenocarcinoma who received treatment. Further research is needed to understand the association of intervals along the whole cancer spectrum (e.g., presentation, diagnosis, treatment) and longer treatment intervals (i.e., >12 weeks) with survival.</div></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":"25 2","pages":"Pages 234-240"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903414","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 : 2025-03-01DOI: 10.1016/j.pan.2025.01.011
Mike J.P. de Jong , Foke van Delft , Fer D.W. Radstake , Tom H. Perik , Geke Litjens , Tanya M. Bisseling , Fons van der Sommen , Erwin-Jan M. van Geenen , John J. Hermans , Peter D. Siersema
Background
Pancreatic ductal adenocarcinoma (PDAC) still has a dismal 5-year overall survival of 13 %. Chemotherapy is increasingly used as treatment in both (neo-) adjuvant and palliative conditions. However, the overall survival benefits of chemotherapy must be weighed against significant side effects leading to a reduction in quality of life. CE-EUS and elastography could provide additional information about the vascularization and elasticity of the pancreatic tumor. The aim of this study was to investigate if contrast-enhanced endoscopic ultrasound and/or elastography could be suitable to predict the effectiveness of FOLFIRINOX.
Methods
Single center, prospective proof-of-concept study in which intravenous contrast agent was administered and strain ratio was calculated in patients undergoing EUS in their regular diagnostic work-up. Directly after contrast administration, a video of 120 s was recorded and afterwards tracked and fitted by a Modified Local Density Random Walk (mLDRW) model.
Results
We included 17 patients. Based on cross-sectional imaging based RECIST criteria, chemotherapy treatment was effective in 11 patients and not effective in 6 patients. The contrast dispersion parameter (κ1) differed significantly between both groups in favor of the responders: 2.994 (IQR 1.670–5.170) vs 1.203 (IQR 0.953–1.756), p = 0.005. The elastography strain ratio was higher in the effectively treated group (20.9 vs 13.6, p = 0.138).
Conclusion
This proof-of-concept study showed that the dispersion parameter of the first wave of contrast was 2.5 times higher in patients in whom FOLFIRINOX was effective, suggesting that this parameter could possibly be a reliable prediction tool.
{"title":"Contrast agent dispersion visualized by CE-EUS may be a prediction tool for FOLFIRINOX chemotherapy effectiveness in patients with pancreatic adenocarcinoma","authors":"Mike J.P. de Jong , Foke van Delft , Fer D.W. Radstake , Tom H. Perik , Geke Litjens , Tanya M. Bisseling , Fons van der Sommen , Erwin-Jan M. van Geenen , John J. Hermans , Peter D. Siersema","doi":"10.1016/j.pan.2025.01.011","DOIUrl":"10.1016/j.pan.2025.01.011","url":null,"abstract":"<div><h3>Background</h3><div>Pancreatic ductal adenocarcinoma (PDAC) still has a dismal 5-year overall survival of 13 %. Chemotherapy is increasingly used as treatment in both (neo-) adjuvant and palliative conditions. However, the overall survival benefits of chemotherapy must be weighed against significant side effects leading to a reduction in quality of life. CE-EUS and elastography could provide additional information about the vascularization and elasticity of the pancreatic tumor. The aim of this study was to investigate if contrast-enhanced endoscopic ultrasound and/or elastography could be suitable to predict the effectiveness of FOLFIRINOX.</div></div><div><h3>Methods</h3><div>Single center, prospective proof-of-concept study in which intravenous contrast agent was administered and strain ratio was calculated in patients undergoing EUS in their regular diagnostic work-up. Directly after contrast administration, a video of 120 s was recorded and afterwards tracked and fitted by a Modified Local Density Random Walk (mLDRW) model.</div></div><div><h3>Results</h3><div>We included 17 patients. Based on cross-sectional imaging based RECIST criteria, chemotherapy treatment was effective in 11 patients and not effective in 6 patients. The contrast dispersion parameter (κ1) differed significantly between both groups in favor of the responders: 2.994 (IQR 1.670–5.170) vs 1.203 (IQR 0.953–1.756), p = 0.005. The elastography strain ratio was higher in the effectively treated group (20.9 vs 13.6, p = 0.138).</div></div><div><h3>Conclusion</h3><div>This proof-of-concept study showed that the dispersion parameter of the first wave of contrast was 2.5 times higher in patients in whom FOLFIRINOX was effective, suggesting that this parameter could possibly be a reliable prediction tool.</div></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":"25 2","pages":"Pages 258-265"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256141","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 : 2025-03-01DOI: 10.1016/j.pan.2025.01.008
Jing Zhou , Lanting Wang , Tao Chen , Chao Li , Yue Long , Xinsen Zou , Zhouzhou Dong , Yun Sun , Guoxiu Zhang , Zhenguo Zeng , Gang Li , Bo Ye , Longxiang Cao , Lu Ke , Yuxiu Liu , Zhihui Tong , Weiqin Li , for the Chinese Acute Pancreatitis Clinical Trials Group (CAPCTG)
Background
The prevalence of hypertriglyceridemia-associated acute pancreatitis (HTG-AP) is increasing. Studies have demonstrated the association between higher initial plasma triglyceride (TG) levels and worse clinical prognosis; therefore, lowering plasma TG has been the mainstay when managing HTG-AP. For TG-lowering therapy, plasmapheresis, which is costly and of potential complications, is currently widely used to clear TG from plasma, but whether it confers clinical benefits is unclear. In this trial, we aimed to evaluate the effect of plasmapheresis versus standard medical treatment on the duration of organ failure in HTG-AP patients with early organ failure.
Methods
This is a multicenter, pragmatic, registry-based, randomized controlled trial. Based on previous studies, up to 236 HTG-AP patients with early organ failure are projected to be randomly assigned to either the plasmapheresis group or the standard medical treatment group (insulin plus low molecular weight heparin therapy). The PERFORM registry will be used as the platform for patient enrollment. The primary outcome is organ failure-free days to 14 days of enrollment. Organ failure in this trial is defined as an individual sequential organ failure assessment (SOFA) score of two or more for the respiratory, cardiovascular, or renal system. Patients who died before day 14 will be assigned zero organ failure-free days.
Discussion
This trial will provide top-class evidence regarding the clinical impact of plasmapheresis in HTG-AP patients with early organ failure. The findings of this trial will have a direct influence on the current clinical practice concerning the management of HTG-AP.
{"title":"Effect of plasmapheresis versus standard medical treatment in patients with hypertriglyceridemia-associated acute pancreatitis complicated by early organ failure (PERFORM-R): Study design and rationale of a multicenter, pragmatic, registry-based randomized controlled trial","authors":"Jing Zhou , Lanting Wang , Tao Chen , Chao Li , Yue Long , Xinsen Zou , Zhouzhou Dong , Yun Sun , Guoxiu Zhang , Zhenguo Zeng , Gang Li , Bo Ye , Longxiang Cao , Lu Ke , Yuxiu Liu , Zhihui Tong , Weiqin Li , for the Chinese Acute Pancreatitis Clinical Trials Group (CAPCTG)","doi":"10.1016/j.pan.2025.01.008","DOIUrl":"10.1016/j.pan.2025.01.008","url":null,"abstract":"<div><h3>Background</h3><div>The prevalence of hypertriglyceridemia-associated acute pancreatitis (HTG-AP) is increasing. Studies have demonstrated the association between higher initial plasma triglyceride (TG) levels and worse clinical prognosis; therefore, lowering plasma TG has been the mainstay when managing HTG-AP. For TG-lowering therapy, plasmapheresis, which is costly and of potential complications, is currently widely used to clear TG from plasma, but whether it confers clinical benefits is unclear. In this trial, we aimed to evaluate the effect of plasmapheresis versus standard medical treatment on the duration of organ failure in HTG-AP patients with early organ failure.</div></div><div><h3>Methods</h3><div>This is a multicenter, pragmatic, registry-based, randomized controlled trial. Based on previous studies, up to 236 HTG-AP patients with early organ failure are projected to be randomly assigned to either the plasmapheresis group or the standard medical treatment group (insulin plus low molecular weight heparin therapy). The PERFORM registry will be used as the platform for patient enrollment. The primary outcome is organ failure-free days to 14 days of enrollment. Organ failure in this trial is defined as an individual sequential organ failure assessment (SOFA) score of two or more for the respiratory, cardiovascular, or renal system. Patients who died before day 14 will be assigned zero organ failure-free days.</div></div><div><h3>Discussion</h3><div>This trial will provide top-class evidence regarding the clinical impact of plasmapheresis in HTG-AP patients with early organ failure. The findings of this trial will have a direct influence on the current clinical practice concerning the management of HTG-AP.</div></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":"25 2","pages":"Pages 221-227"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075230","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}
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