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Medicine â€ș Oncology

Pancreatic and Hepatic Oncology Research

Works Count: 129899

Description

This cluster of papers focuses on the research and treatment of pancreatic cancer, covering topics such as surgical complications, chemotherapy regimens (e.g., Gemcitabine), tumor microenvironment, genomic analyses, stromal biology, neoadjuvant therapy, and immunotherapy. The papers also discuss the impact of hospital volume on surgical outcomes and the prevalence of pancreatic cysts.

Keywords

Pancreatic Cancer; Surgical Complications; Gemcitabine; Tumor Microenvironment; Genomic Analyses; Chemotherapy; Stromal Biology; Neoadjuvant Therapy; Metastatic Pancreatic Cancer; Immunotherapy

Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma

2015-09-07
Richard A. Moffitt , Raoud Marayati , Elizabeth L. Flate +7 more

Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial.

1997-06-01
Howard A. Burris , Malcolm J. Moore , John Sahl Andersen +7 more
PURPOSE Most patients with advanced pancreas cancer experience pain and must limit their daily activities because of tumor-related symptoms. To date, no treatment has had a significant impact on the 
 PURPOSE Most patients with advanced pancreas cancer experience pain and must limit their daily activities because of tumor-related symptoms. To date, no treatment has had a significant impact on the disease. In early studies with gemcitabine, patients with pancreas cancer experienced an improvement in disease-related symptoms. Based on those findings, a definitive trial was performed to assess the effectiveness of gemcitabine in patients with newly diagnosed advanced pancreas cancer. PATIENTS AND METHODS One hundred twenty-six patients with advanced symptomatic pancreas cancer completed a lead-in period to characterize and stabilize pain and were randomized to receive either gemcitabine 1,000 mg/m2 weekly x 7 followed by 1 week of rest, then weekly x 3 every 4 weeks thereafter (63 patients), or to fluorouracil (5-FU) 600 mg/m2 once weekly (63 patients). The primary efficacy measure was clinical benefit response, which was a composite of measurements of pain (analgesic consumption and pain intensity), Karnofsky performance status, and weight. Clinical benefit required a sustained (> or = 4 weeks) improvement in at least one parameter without worsening in any others. Other measures of efficacy included response rate, time to progressive disease, and survival. RESULTS Clinical benefit response was experienced by 23.8% of gemcitabine-treated patients compared with 4.8% of 5-FU-treated patients (P = .0022). The median survival durations were 5.65 and 4.41 months for gemcitabine-treated and 5-FU-treated patients, respectively (P = .0025). The survival rate at 12 months was 18% for gemcitabine patients and 2% for 5-FU patients. Treatment was well tolerated. CONCLUSION This study demonstrates that gemcitabine is more effective than 5-FU in alleviation of some disease-related symptoms in patients with advanced, symptomatic pancreas cancer. Gemcitabine also confers a modest survival advantage over treatment with 5-FU.

Resected adenocarcinoma of the pancreas—616 patients: results, outcomes, and prognostic indicators

2000-11-01
Taylor A. Sohn , Charles J. Yeo , John L. Cameron +7 more

Six Hundred Fifty Consecutive Pancreaticoduodenectomies in the 1990s

1997-09-01
Charles J. Yeo , John L. Cameron , Taylor A. Sohn +7 more
Objective The authors reviewed the pathology, complications, and outcomes in a consecutive group of 650 patients undergoing pancreaticoduodenectomy in the 1990s. Summary Background Data Pancreaticoduodenectomy has been used increasingly in 
 Objective The authors reviewed the pathology, complications, and outcomes in a consecutive group of 650 patients undergoing pancreaticoduodenectomy in the 1990s. Summary Background Data Pancreaticoduodenectomy has been used increasingly in recent years to resect a variety of malignant and benign diseases of the pancreas and periampullary region. Methods Between January 1990 and July 1996, inclusive, 650 patients underwent pancreaticoduodenal resection at The Johns Hopkins Hospital. Data were recorded prospectively on all patients. All pathology specimens were reviewed and categorized. Statistical analyses were performed using both univariate and multivariate models. Results The patients had a mean age of 63 ± 12.8 years, with 54% male and 91% white. The number of resections per year rose from 60 in 1990 to 161 in 1995. Pathologic examination results showed pancreatic cancer (n = 282; 43%), ampullary cancer (n = 70; 11%), distal common bile duct cancer (n = 65; 10%), duodenal cancer (n = 26; 4%), chronic pancreatitis (n = 71; 11%), neuroendocrine tumor (n = 31; 5%), periampullary adenoma (n = 21; 3%), cystadenocarcinoma (n = 14; 2%), cystadenoma (n = 25; 4%), and other (n = 45; 7%). The surgical procedure involved pylorus preservation in 82%, partial pancreatectomy in 95%, and portal or superior mesenteric venous resection in 4%. Pancreatic-enteric reconstruction, when appropriate, was via pancreaticojejunostomy in 71% and pancreaticogastrostomy in 29%. The median intraoperative blood loss was 625 mL, median units of red cells transfused was zero, and the median operative time was 7 hours. During this period, 190 consecutive pancreaticoduodenectomies were performed without a mortality. Nine deaths occurred in-hospital or within 30 days of operation (1.4% operative mortality). The postoperative complication rate was 41%, with the most common complications being early delayed gastric emptying (19%), pancreatic fistula (14%), and wound infection (10%). Twenty-three patients required reoperation in the immediate postoperative period (3.5%), most commonly for bleeding, abscess, or dehiscence. The median postoperative length of stay was 13 days. A multivariate analysis of the 443 patients with periampullary adenocarcinoma indicated that the most powerful independent predictors favoring long-term survival included a pathologic diagnosis of duodenal adenocarcinoma, tumor diameter <3 cm, negative resection margins, absence of lymph node metastases, well-differentiated histology, and no reoperation. Conclusions This single institution, high-volume experience indicates that pancreaticoduodenectomy can be performed safely for a variety of malignant and benign disorders of the pancreas and periampullary region. Overall survival is determined largely by the pathology within the resection specimen.

Whole genomes redefine the mutational landscape of pancreatic cancer

2015-02-24
Nicola Waddell , Marina Pajic , Ann‐Marie Patch +7 more

Delayed gastric emptying (DGE) after pancreatic surgery: A suggested definition by the International Study Group of Pancreatic Surgery (ISGPS)

2007-11-01
Moritz N. Wente , Claudio Bassi , Christos Dervenis +7 more

Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice

2005-05-01
Sunil R. Hingorani , Lifu Wang , Asha S. Multani +6 more

Organoid Models of Human and Mouse Ductal Pancreatic Cancer

2014-12-31
Sylvia F. Boj , Chang‐Il Hwang , Lindsey A. Baker +7 more
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EMT and Dissemination Precede Pancreatic Tumor Formation

2012-01-01
Andrew D. Rhim , Emily T. Mirek , Nicole M. Aiello +7 more
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A Randomized Trial of Chemoradiotherapy and Chemotherapy after Resection of Pancreatic Cancer

2004-03-17
John P. Neoptolemos , Deborah Stocken , Helmut Friess +7 more
The effect of adjuvant treatment on survival in pancreatic cancer is unclear. We report the final results of the European Study Group for Pancreatic Cancer 1 Trial and update the 
 The effect of adjuvant treatment on survival in pancreatic cancer is unclear. We report the final results of the European Study Group for Pancreatic Cancer 1 Trial and update the interim results.In a multicenter trial using a two-by-two factorial design, we randomly assigned 73 patients with resected pancreatic ductal adenocarcinoma to treatment with chemoradiotherapy alone (20 Gy over a two-week period plus fluorouracil), 75 patients to chemotherapy alone (fluorouracil), 72 patients to both chemoradiotherapy and chemotherapy, and 69 patients to observation.The analysis was based on 237 deaths among the 289 patients (82 percent) and a median follow-up of 47 months (interquartile range, 33 to 62). The estimated five-year survival rate was 10 percent among patients assigned to receive chemoradiotherapy and 20 percent among patients who did not receive chemoradiotherapy (P=0.05). The five-year survival rate was 21 percent among patients who received chemotherapy and 8 percent among patients who did not receive chemotherapy (P=0.009). The benefit of chemotherapy persisted after adjustment for major prognostic factors.Adjuvant chemotherapy has a significant survival benefit in patients with resected pancreatic cancer, whereas adjuvant chemoradiotherapy has a deleterious effect on survival.
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Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse

2003-12-01
Sunil R. Hingorani , Emanuel F. Petricoin , Anirban Maitra +7 more

Depletion of Carcinoma-Associated Fibroblasts and Fibrosis Induces Immunosuppression and Accelerates Pancreas Cancer with Reduced Survival

2014-05-22
Berna C. Özdemir , Tsvetelina Pentcheva‐Hoang , Julienne L. Carstens +7 more
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Genetics and biology of pancreatic ductal adenocarcinoma.

2006-05-15
Aram F. Hezel , Alec C. Kimmelman , Ben Z. Stanger +2 more
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the United States with a median survival of <6 mo and a dismal 5-yr survival rate of 
 Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the United States with a median survival of <6 mo and a dismal 5-yr survival rate of 3%-5%. The cancer's lethal nature stems from its propensity to rapidly disseminate to the lymphatic system and distant organs. This aggressive biology and resistance to conventional and targeted therapeutic agents leads to a typical clinical presentation of incurable disease at the time of diagnosis. The well-defined serial histopathologic picture and accompanying molecular profiles of PDAC and its precursor lesions have provided the framework for emerging basic and translational research. Recent advances include insights into the cancer's cellular origins, high-resolution genomic profiles pointing to potential new therapeutic targets, and refined mouse models reflecting both the genetics and histopathologic evolution of human PDAC. This confluence of developments offers the opportunity for accelerated discovery and the future promise of improved treatment.
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International Consensus Guidelines for Management of Intraductal Papillary Mucinous Neoplasms and Mucinous Cystic Neoplasms of the Pancreas

2005-11-30
Masao Tanaka , Suresh T. Chari , Volkan Adsay +6 more

<i>DPC4</i> , A Candidate Tumor Suppressor Gene at Human Chromosome 18q21.1

1996-01-19
Stephan A. Hahn , Mieke Schutte , A.T.M. Shamsul Hoque +7 more
About 90 percent of human pancreatic carcinomas show allelic loss at chromosome 18q. To identify candidate tumor suppressor genes on 18q, a panel of pancreatic carcinomas were analyzed for convergent 
 About 90 percent of human pancreatic carcinomas show allelic loss at chromosome 18q. To identify candidate tumor suppressor genes on 18q, a panel of pancreatic carcinomas were analyzed for convergent sites of homozygous deletion. Twenty-five of 84 tumors had homozygous deletions at 18q21.1, a site that excludes DCC (a candidate suppressor gene for colorectal cancer) and includes DPC4 , a gene similar in sequence to a Drosophila melanogaster gene ( Mad ) implicated in a transforming growth factor-ÎČ (TGF-ÎČ)-like signaling pathway. Potentially inactivating mutations in DPC4 were identified in six of 27 pancreatic carcinomas that did not have homozygous deletions at 18q21.1. These results identify DPC4 as a candidate tumor suppressor gene whose inactivation may play a role in pancreatic and possibly other human cancers.

Bile leakage after hepatobiliary and pancreatic surgery: A definition and grading of severity by the International Study Group of Liver Surgery

2011-02-15
Moritz Koch , O. James Garden , Robert Padbury +7 more

Postoperative pancreatic fistula: An international study group (ISGPF) definition

2005-07-01
Claudio Bassi , Christos Dervenis , Giovanni Butturini +7 more

Adjuvant Chemotherapy With Gemcitabine vs Observation in Patients Undergoing Curative-Intent Resection of Pancreatic Cancer

2007-01-17
Helmut Oettle , Stefan Post , P. Neuhaus +7 more
ITH AN ESTIMATED NUMber of 232 000 new cases per year, pancreatic cancer is among the most common malignancies worldwide. 1Moreover, it is one of the most lethal cancers, as 
 ITH AN ESTIMATED NUMber of 232 000 new cases per year, pancreatic cancer is among the most common malignancies worldwide. 1Moreover, it is one of the most lethal cancers, as indicated by a mortality incidence ratio of 98%. 1 Pancreatic cancer is the fourth leading cause of death from cancer in the United States, with 32 300 deaths estimated in 2006. 2 Sur-See also p 311 and Patient Page.

Posthepatectomy liver failure: A definition and grading by the International Study Group of Liver Surgery (ISGLS)

2011-01-15
Nuh N. Rahbari , O. James Garden , Robert Padbury +7 more

Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses

2008-09-04
SiĂąn Jones , Yun Han , D. Williams Parsons +7 more
There are currently few therapeutic options for patients with pancreatic cancer, and new insights into the pathogenesis of this lethal disease are urgently needed. Toward this end, we performed a 
 There are currently few therapeutic options for patients with pancreatic cancer, and new insights into the pathogenesis of this lethal disease are urgently needed. Toward this end, we performed a comprehensive genetic analysis of 24 pancreatic cancers. We first determined the sequences of 23,219 transcripts, representing 20,661 protein-coding genes, in these samples. Then, we searched for homozygous deletions and amplifications in the tumor DNA by using microarrays containing probes for approximately 10(6) single-nucleotide polymorphisms. We found that pancreatic cancers contain an average of 63 genetic alterations, the majority of which are point mutations. These alterations defined a core set of 12 cellular signaling pathways and processes that were each genetically altered in 67 to 100% of the tumors. Analysis of these tumors' transcriptomes with next-generation sequencing-by-synthesis technologies provided independent evidence for the importance of these pathways and processes. Our data indicate that genetically altered core pathways and regulatory processes only become evident once the coding regions of the genome are analyzed in depth. Dysregulation of these core pathways and processes through mutation can explain the major features of pancreatic tumorigenesis.
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Adjuvant Chemotherapy With Gemcitabine and Long-term Outcomes Among Patients With Resected Pancreatic Cancer

2013-10-08
Helmut Oettle , P. Neuhaus , Andreas Hochhaus +7 more
The prognosis for patients with pancreatic cancer is poor, even after resection with curative intent. Gemcitabine-based chemotherapy is standard treatment for advanced pancreatic cancer, but its effect on survival in 
 The prognosis for patients with pancreatic cancer is poor, even after resection with curative intent. Gemcitabine-based chemotherapy is standard treatment for advanced pancreatic cancer, but its effect on survival in the adjuvant setting has not been demonstrated.To analyze whether previously reported improvement in disease-free survival with adjuvant gemcitabine therapy translates into improved overall survival.CONKO-001 (Charité Onkologie 001), a multicenter, open-label, phase 3 randomized trial to evaluate the efficacy and toxicity of gemcitabine in patients with pancreatic cancer after complete tumor resection. Patients with macroscopically completely removed pancreatic cancer entered the study between July 1998 and December 2004 in 88 hospitals in Germany and Austria. Follow-up ended in September 2012.After stratification for tumor stage, nodal status, and resection status, patients were randomly assigned to either adjuvant gemcitabine treatment (1g/m2 d 1, 8, 15, q 4 weeks) for 6 months or to observation alone.The primary end point was disease-free survival. Secondary end points included treatment safety and overall survival, with overall survival defined as the time from date of randomization to death. Patients lost to follow-up were censored on the date of their last follow-up.A total of 368 patients were randomized, and 354 were eligible for intention-to-treat-analysis. By September 2012, 308 patients (87.0% [95% CI, 83.1%-90.1%]) had relapsed and 316 patients (89.3% [95% CI, 85.6%-92.1%]) had died. The median follow-up time was 136 months. The median disease-free survival was 13.4 (95% CI, 11.6-15.3) months in the treatment group compared with 6.7 (95% CI, 6.0-7.5) months in the observation group (hazard ratio, 0.55 [95% CI, 0.44-0.69]; P < .001). Patients randomized to adjuvant gemcitabine treatment had prolonged overall survival compared with those randomized to observation alone (hazard ratio, 0.76 [95% CI, 0.61-0.95]; P = .01), with 5-year overall survival of 20.7% (95% CI, 14.7%-26.6%) vs 10.4% (95% CI, 5.9%-15.0%), respectively, and 10-year overall survival of 12.2% (95% CI, 7.3%-17.2%) vs 7.7% (95% CI, 3.6%-11.8%).Among patients with macroscopic complete removal of pancreatic cancer, the use of adjuvant gemcitabine for 6 months compared with observation alone resulted in increased overall survival as well as disease-free survival. These findings provide strong support for the use of gemcitabine in this setting.isrctn.org Identifier: ISRCTN34802808.

International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas

2012-05-01
Masao Tanaka , Carlos FernĂĄndez-del Castillo , Volkan Adsay +7 more

FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer

2011-05-11
Thierry Conroy , Françoise Desseigne , Marc Ychou +7 more
Data are lacking on the efficacy and safety of a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) as compared with gemcitabine as first-line therapy in patients 
 Data are lacking on the efficacy and safety of a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) as compared with gemcitabine as first-line therapy in patients with metastatic pancreatic cancer.We randomly assigned 342 patients with an Eastern Cooperative Oncology Group performance status score of 0 or 1 (on a scale of 0 to 5, with higher scores indicating a greater severity of illness) to receive FOLFIRINOX (oxaliplatin, 85 mg per square meter of body-surface area; irinotecan, 180 mg per square meter; leucovorin, 400 mg per square meter; and fluorouracil, 400 mg per square meter given as a bolus followed by 2400 mg per square meter given as a 46-hour continuous infusion, every 2 weeks) or gemcitabine at a dose of 1000 mg per square meter weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. Six months of chemotherapy were recommended in both groups in patients who had a response. The primary end point was overall survival.The median overall survival was 11.1 months in the FOLFIRINOX group as compared with 6.8 months in the gemcitabine group (hazard ratio for death, 0.57; 95% confidence interval [CI], 0.45 to 0.73; P<0.001). Median progression-free survival was 6.4 months in the FOLFIRINOX group and 3.3 months in the gemcitabine group (hazard ratio for disease progression, 0.47; 95% CI, 0.37 to 0.59; P<0.001). The objective response rate was 31.6% in the FOLFIRINOX group versus 9.4% in the gemcitabine group (P<0.001). More adverse events were noted in the FOLFIRINOX group; 5.4% of patients in this group had febrile neutropenia. At 6 months, 31% of the patients in the FOLFIRINOX group had a definitive degradation of the quality of life versus 66% in the gemcitabine group (hazard ratio, 0.47; 95% CI, 0.30 to 0.70; P<0.001).As compared with gemcitabine, FOLFIRINOX was associated with a survival advantage and had increased toxicity. FOLFIRINOX is an option for the treatment of patients with metastatic pancreatic cancer and good performance status. (Funded by the French government and others; ClinicalTrials.gov number, NCT00112658.).
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Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy

2011-04-01
Eric A. Collisson , Anguraj Sadanandam , Peter Olson +7 more

Erlotinib Plus Gemcitabine Compared With Gemcitabine Alone in Patients With Advanced Pancreatic Cancer: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group

2007-04-24
Malcolm J. Moore , David Goldstein , John Hamm +7 more
Patients with advanced pancreatic cancer have a poor prognosis and there have been no improvements in survival since the introduction of gemcitabine in 1996. Pancreatic tumors often overexpress human epidermal 
 Patients with advanced pancreatic cancer have a poor prognosis and there have been no improvements in survival since the introduction of gemcitabine in 1996. Pancreatic tumors often overexpress human epidermal growth factor receptor type 1 (HER1/EGFR) and this is associated with a worse prognosis. We studied the effects of adding the HER1/EGFR-targeted agent erlotinib to gemcitabine in patients with unresectable, locally advanced, or metastatic pancreatic cancer.

Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes

2012-10-24
Andrew V. Biankin , Nicola Waddell , Karin S. Kassahn +7 more
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Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes

1988-05-01
ConcepciĂłn Almoguera , Darryl Shibata , Kathleen Forrester +3 more

Postpancreatectomy hemorrhage (PPH)–An International Study Group of Pancreatic Surgery (ISGPS) definition

2007-07-01
Moritz N. Wente , J. Veit , Claudio Bassi +7 more

Increased Survival in Pancreatic Cancer with nab-Paclitaxel plus Gemcitabine

2013-10-16
Daniel D. Von Hoff , Thomas J. Ervin , Francis P. Arena +7 more
In a phase 1-2 trial of albumin-bound paclitaxel (nab-paclitaxel) plus gemcitabine, substantial clinical activity was noted in patients with advanced pancreatic cancer. We conducted a phase 3 study of the 
 In a phase 1-2 trial of albumin-bound paclitaxel (nab-paclitaxel) plus gemcitabine, substantial clinical activity was noted in patients with advanced pancreatic cancer. We conducted a phase 3 study of the efficacy and safety of the combination versus gemcitabine monotherapy in patients with metastatic pancreatic cancer.We randomly assigned patients with a Karnofsky performance-status score of 70 or more (on a scale from 0 to 100, with higher scores indicating better performance status) to nab-paclitaxel (125 mg per square meter of body-surface area) followed by gemcitabine (1000 mg per square meter) on days 1, 8, and 15 every 4 weeks or gemcitabine monotherapy (1000 mg per square meter) weekly for 7 of 8 weeks (cycle 1) and then on days 1, 8, and 15 every 4 weeks (cycle 2 and subsequent cycles). Patients received the study treatment until disease progression. The primary end point was overall survival; secondary end points were progression-free survival and overall response rate.A total of 861 patients were randomly assigned to nab-paclitaxel plus gemcitabine (431 patients) or gemcitabine (430). The median overall survival was 8.5 months in the nab-paclitaxel-gemcitabine group as compared with 6.7 months in the gemcitabine group (hazard ratio for death, 0.72; 95% confidence interval [CI], 0.62 to 0.83; P<0.001). The survival rate was 35% in the nab-paclitaxel-gemcitabine group versus 22% in the gemcitabine group at 1 year, and 9% versus 4% at 2 years. The median progression-free survival was 5.5 months in the nab-paclitaxel-gemcitabine group, as compared with 3.7 months in the gemcitabine group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.58 to 0.82; P<0.001); the response rate according to independent review was 23% versus 7% in the two groups (P<0.001). The most common adverse events of grade 3 or higher were neutropenia (38% in the nab-paclitaxel-gemcitabine group vs. 27% in the gemcitabine group), fatigue (17% vs. 7%), and neuropathy (17% vs. 1%). Febrile neutropenia occurred in 3% versus 1% of the patients in the two groups. In the nab-paclitaxel-gemcitabine group, neuropathy of grade 3 or higher improved to grade 1 or lower in a median of 29 days.In patients with metastatic pancreatic adenocarcinoma, nab-paclitaxel plus gemcitabine significantly improved overall survival, progression-free survival, and response rate, but rates of peripheral neuropathy and myelosuppression were increased. (Funded by Celgene; ClinicalTrials.gov number, NCT00844649.).
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Distant metastasis occurs late during the genetic evolution of pancreatic cancer

2010-10-01
Shinichi Yachida , SiĂąn Jones , Ivana BoĆŸić +7 more
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Genomic analyses identify molecular subtypes of pancreatic cancer

2016-02-23
Peter J. Bailey , David K. Chang , KĂĄtia Nones +7 more

Pancreatitis and the Risk of Pancreatic Cancer

1993-05-20
Albert B. Lowenfels , Patrick Maisonneuve , Giorgio Cavallini +6 more
The results of case-control studies and anecdotal reports suggest that pancreatitis may be a risk factor for pancreatic cancer, but there have been no studies of sufficient size and power 
 The results of case-control studies and anecdotal reports suggest that pancreatitis may be a risk factor for pancreatic cancer, but there have been no studies of sufficient size and power to assess the magnitude of the relation between these two diseases.
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The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 Years After

2016-12-29
Claudio Bassi , Giovanni Marchegiani , Christos Dervenis +7 more

Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial

2017-01-25
John P. Neoptolemos , Daniel H. Palmer , Paula Ghaneh +7 more
BackgroundThe ESPAC-3 trial showed that adjuvant gemcitabine is the standard of care based on similar survival to and less toxicity than adjuvant 5-fluorouracil/folinic acid in patients with resected pancreatic cancer. 
 BackgroundThe ESPAC-3 trial showed that adjuvant gemcitabine is the standard of care based on similar survival to and less toxicity than adjuvant 5-fluorouracil/folinic acid in patients with resected pancreatic cancer. Other clinical trials have shown better survival and tumour response with gemcitabine and capecitabine than with gemcitabine alone in advanced or metastatic pancreatic cancer. We aimed to determine the efficacy and safety of gemcitabine and capecitabine compared with gemcitabine monotherapy for resected pancreatic cancer.MethodsWe did a phase 3, two-group, open-label, multicentre, randomised clinical trial at 92 hospitals in England, Scotland, Wales, Germany, France, and Sweden. Eligible patients were aged 18 years or older and had undergone complete macroscopic resection for ductal adenocarcinoma of the pancreas (R0 or R1 resection). We randomly assigned patients (1:1) within 12 weeks of surgery to receive six cycles of either 1000 mg/m2 gemcitabine alone administered once a week for three of every 4 weeks (one cycle) or with 1660 mg/m2 oral capecitabine administered for 21 days followed by 7 days' rest (one cycle). Randomisation was based on a minimisation routine, and country was used as a stratification factor. The primary endpoint was overall survival, measured as the time from randomisation until death from any cause, and assessed in the intention-to-treat population. Toxicity was analysed in all patients who received trial treatment. This trial was registered with the EudraCT, number 2007-004299-38, and ISRCTN, number ISRCTN96397434.FindingsOf 732 patients enrolled, 730 were included in the final analysis. Of these, 366 were randomly assigned to receive gemcitabine and 364 to gemcitabine plus capecitabine. The Independent Data and Safety Monitoring Committee requested reporting of the results after there were 458 (95%) of a target of 480 deaths. The median overall survival for patients in the gemcitabine plus capecitabine group was 28·0 months (95% CI 23·5–31·5) compared with 25·5 months (22·7–27·9) in the gemcitabine group (hazard ratio 0·82 [95% CI 0·68–0·98], p=0·032). 608 grade 3–4 adverse events were reported by 226 of 359 patients in the gemcitabine plus capecitabine group compared with 481 grade 3–4 adverse events in 196 of 366 patients in the gemcitabine group.InterpretationThe adjuvant combination of gemcitabine and capecitabine should be the new standard of care following resection for pancreatic ductal adenocarcinoma.FundingCancer Research UK.
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Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer

2017-02-23
Daniel Öhlund , Abram Handly-Santana , Giulia Biffi +7 more
Pancreatic stellate cells (PSCs) differentiate into cancer-associated fibroblasts (CAFs) that produce desmoplastic stroma, thereby modulating disease progression and therapeutic response in pancreatic ductal adenocarcinoma (PDA). However, it is unknown whether 
 Pancreatic stellate cells (PSCs) differentiate into cancer-associated fibroblasts (CAFs) that produce desmoplastic stroma, thereby modulating disease progression and therapeutic response in pancreatic ductal adenocarcinoma (PDA). However, it is unknown whether CAFs uniformly carry out these tasks or if subtypes of CAFs with distinct phenotypes in PDA exist. We identified a CAF subpopulation with elevated expression of α-smooth muscle actin (αSMA) located immediately adjacent to neoplastic cells in mouse and human PDA tissue. We recapitulated this finding in co-cultures of murine PSCs and PDA organoids, and demonstrated that organoid-activated CAFs produced desmoplastic stroma. The co-cultures showed cooperative interactions and revealed another distinct subpopulation of CAFs, located more distantly from neoplastic cells, which lacked elevated αSMA expression and instead secreted IL6 and additional inflammatory mediators. These findings were corroborated in mouse and human PDA tissue, providing direct evidence for CAF heterogeneity in PDA tumor biology with implications for disease etiology and therapeutic development.
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Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas

2017-07-13
Masao Tanaka , Carlos Fernández–del Castillo , Terumi Kamisawa +7 more

Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma

2017-08-01
Benjamin J. Raphael , Ralph H. Hruban , Andrew J. Aguirre +7 more
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Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes

2018-11-20
Andrew McGuigan , Paul Kelly , Richard Turkington +3 more
Risk of recurrence of primary sclerosing cholangitis after Risk of recurrence of primary sclerosing cholangitis after
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FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer

2018-12-19
Thierry Conroy , Pascal Hammel , Mohamed Hebbar +7 more
Among patients with metastatic pancreatic cancer, combination chemotherapy with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) leads to longer overall survival than gemcitabine therapy. We compared the efficacy and safety of 
 Among patients with metastatic pancreatic cancer, combination chemotherapy with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) leads to longer overall survival than gemcitabine therapy. We compared the efficacy and safety of a modified FOLFIRINOX regimen with gemcitabine as adjuvant therapy in patients with resected pancreatic cancer.
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Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors

2019-01-01
Prashanth Rawla , Tagore Sunkara , Vinaya Gaduputi
Pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide. However, its toll is higher in more developed countries. Reasons for vast differences in mortality rates of pancreatic cancer 
 Pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide. However, its toll is higher in more developed countries. Reasons for vast differences in mortality rates of pancreatic cancer are not completely clear yet, but it may be due to lack of appropriate diagnosis, treatment and cataloging of cancer cases. Because patients seldom exhibit symptoms until an advanced stage of the disease, pancreatic cancer remains one of the most lethal malignant neoplasms that caused 432,242 new deaths in 2018 (GLOBOCAN 2018 estimates). Globally, 458,918 new cases of pancreatic cancer have been reported in 2018, and 355,317 new cases are estimated to occur until 2040. Despite advancements in the detection and management of pancreatic cancer, the 5-year survival rate still stands at 9% only. To date, the causes of pancreatic carcinoma are still insufficiently known, although certain risk factors have been identified, such as tobacco smoking, diabetes mellitus, obesity, dietary factors, alcohol abuse, age, ethnicity, family history and genetic factors, Helicobacter pylori infection , non-O blood group and chronic pancreatitis. In general population, screening of large groups is not considered useful to detect the disease at its early stage, although newer techniques and the screening of tightly targeted groups (especially of those with family history), are being evaluated. Primary prevention is considered of utmost importance. Up-to-date statistics on pancreatic cancer occurrence and outcome along with a better understanding of the etiology and identifying the causative risk factors are essential for the primary prevention of this disease. World J Oncol. 2019;10(1):10-27 doi: https://doi.org/10.14740/wjon1166
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Cross-Species Single-Cell Analysis of Pancreatic Ductal Adenocarcinoma Reveals Antigen-Presenting Cancer-Associated Fibroblasts

2019-06-13
Ela Elyada , Mohan Bolisetty , Pasquale Laise +7 more
Cancer-associated fibroblasts (CAF) are major players in the progression and drug resistance of pancreatic ductal adenocarcinoma (PDAC). CAFs constitute a diverse cell population consisting of several recently described subtypes, although 
 Cancer-associated fibroblasts (CAF) are major players in the progression and drug resistance of pancreatic ductal adenocarcinoma (PDAC). CAFs constitute a diverse cell population consisting of several recently described subtypes, although the extent of CAF heterogeneity has remained undefined. Here we use single-cell RNA sequencing to thoroughly characterize the neoplastic and tumor microenvironment content of human and mouse PDAC tumors. We corroborate the presence of myofibroblastic CAFs and inflammatory CAFs and define their unique gene signatures in vivo. Moreover, we describe a new population of CAFs that express MHC class II and CD74, but do not express classic costimulatory molecules. We term this cell population "antigen-presenting CAFs" and find that they activate CD4+ T cells in an antigen-specific fashion in a model system, confirming their putative immune-modulatory capacity. Our cross-species analysis paves the way for investigating distinct functions of CAF subtypes in PDAC immunity and progression. SIGNIFICANCE: Appreciating the full spectrum of fibroblast heterogeneity in pancreatic ductal adenocarcinoma is crucial to developing therapies that specifically target tumor-promoting CAFs. This work identifies MHC class II-expressing CAFs with a capacity to present antigens to CD4+ T cells, and potentially to modulate the immune response in pancreatic tumors.See related commentary by Belle and DeNardo, p. 1001.This article is highlighted in the In This Issue feature, p. 983.
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The 2019 WHO classification of tumours of the digestive system

2019-08-21
Irıs D. Nagtegaal , Robert D. Odze , David S. Klimstra +6 more
The WHO classification of digestive system tumours presented in the first volume of the WHO classification of tumours series, 5th edition, reflects important advancements in our understanding of tumours of 
 The WHO classification of digestive system tumours presented in the first volume of the WHO classification of tumours series, 5th edition, reflects important advancements in our understanding of tumours of the digestive system (Table 1). For the first time, certain tumour types are defined as much by their molecular phenotype as their histological characteristics; however, in most instances histopathological classification remains the gold standard for diagnosis. The WHO classification of tumours series is designed to be used worldwide, including those settings where a lack of tissue samples or of specific technical facilities limits the pathologist's ability to rely on molecular testing. Since the publication of the 4th-edition digestive system tumours volume in 2010,1 there have been important developments in our understanding of the aetiology and pathogenesis of many tumours. However, the extent to which this new information has altered clinical practice has been quite variable. For some of the tumours described in this volume there is little molecular pathology in clinical use, despite the fact that we now have a more detailed understanding of their molecular pathogenesis. A tumour's molecular pathology, as defined for the purposes of this publication, concerns the molecular markers that are relevant to the tumour's diagnosis, biological behaviour, outcome and treatment, rather than its molecular pathogenesis. However, the role of molecular pathology is expanding; for some tumour entities, molecular analysis is now essential for establishing an accurate diagnosis. Some of these analyses require investigation of somatic (acquired) genetic alterations, gene or protein expression, or even circulating tumour markers. For certain tumour types, specific analytical tests are needed to predict prognosis or tumour progression, and these tests are carefully outlined in this volume. In the following paragraphs, we have summarised some of the more notable changes since the 4th edition. In instances where the new WHO classification of tumours editorial board determined that there was insufficient evidence of the diagnostic or clinical relevance of new information about a particular tumour entity, the position held in the 4th edition has been maintained as the standard in the new volume. There has been substantial progress in our understanding of the development of glandular oesophageal neoplasia and the sequential neoplastic progression from inflammation to metaplasia (Barrett's oesophagus), dysplasia and, ultimately, adenocarcinoma. This process is initially driven by gastro-oesophageal reflux disease, which leads to reprogramming of cell differentiation and proliferation in the oesophagus. There is evidence that TP53 mutation in proliferating epithelium leads to high-grade dysplasia, while SMAD4 mutation precedes the development of invasive carcinoma. While demonstration of these mutations is not required clinically, testing oesophageal and gastric adenocarcinomas for ERBB2 [human epidermal growth factor receptor 2 (HER2)] is recommended, as this influences treatment decisions. The pathogenesis of precursor lesions is less clear in oesophageal squamous carcinogenesis than in gastric carcinogenesis. Environmental factors are believed to play an important role, but the mechanisms of neoplastic change as a result of specific factors, such as tobacco use and alcohol consumption, are poorly understood. For example, human papillomavirus (HPV) infection was initially believed to play a key role in squamous carcinogenesis, but recent evidence suggests that there is no such association in most cases of oesophageal squamous cell carcinoma. The molecular pathway of cancer progression in the stomach is less clear. Most epidemic gastric cancers are now considered inflammation-driven, and their aetiology is characteristically environmental – usually related to Helicobacter pylori infection. It is because of this infectious aetiology that gastric cancer is included among the limited number of highly lethal, but preventable, cancers. Chronic gastric inflammation leads to changes in the microenvironment (including the microbiome) that results in mucosal atrophy/metaplasia, which may then progress to neoplasia after further molecular alterations. Metaplastic changes in the upper gastrointestinal tract are well-recognised as early cancer precursors, but their precise molecular mechanisms and the exact role of progenitor cells in the oncogenic cascade remain a subject of intense investigation. For some rare tumours, distinctive driver mutations have been identified; for example, the characteristic MALAT1–GLI1 fusion gene in gastroblastoma and EWSR1 fusions in gastrointestinal clear cell sarcoma and malignant gastrointestinal neuroectodermal tumour. In both examples, demonstration of the fusion gene is now required for the diagnosis. The pathogenesis of adenocarcinomas of the intestines (the small and large bowel and the appendix) is now much better delineated than it was a decade ago. The introduction of population-based screening for colorectal cancer has laid the foundation for a better understanding of neoplastic precursor lesions and the molecular pathways associated with each type of tumour. For example, our knowledge of the molecular pathways and biological behaviour of conventional adenomas and serrated precursor lesions, including the recently renamed sessile serrated lesion (formerly called sessile serrated polyp/adenoma), has grown rapidly in the past decade, and this has enabled clinicians to provide tailored, evidence-driven screening and surveillance programmes. Colorectal cancers, in which it will make a difference to patient treatment, should undergo molecular testing for microsatellite instability and extended RAS testing for mutations in KRAS, NRAS and BRAF. Our understanding of appendiceal tumours has also improved. For example, we now know that many tumours of the appendix develop via neoplastic precursor lesions similar to those in the small and large intestines, and the biological potential and molecular pathways of appendiceal tumours are therefore much better appreciated. The recently renamed goblet cell adenocarcinoma (formerly called goblet cell carcinoid/carcinoma) of the appendix is a prime example of a tumour whose biological potential and histological characteristics have been better described, resulting in improvements in the pathological approach to these tumours. Studies of the aetiology and pathogenesis of anal squamous lesions suggests that HPV infection plays an important aetiological role, driving genetic alterations similar to those in cervical cancer. p16 and HPV testing are recommended for such lesions. One particularly important change in the 5th edition is in the classification of neuroendocrine neoplasms (NENs), which occur in multiple sites throughout the body. In this volume, NENs are covered within each organ-specific chapter, including the chapter on tumours of the pancreas, where detailed sections describing each functioning and non-functioning subtype are provided. Previously, these neoplasms were covered only in the volume on tumours of endocrine organs.2 The general principles guiding the classification of all NENs are presented in a separate introduction to this topic (Table 2). To consolidate our increased understanding of the genetics of these neoplasms, a group of experts met for a consensus conference at the International Agency for Research on Cancer (IARC) in November 2017 and subsequently published a paper in which they proposed distinguishing between well-differentiated neuroendocrine tumours (NETs) and poorly differentiated neuroendocrine carcinomas (NECs) in all sites where these neoplasms arise.3 NEN are divided into NET and NECs, based on their molecular differences. Mutations in MEN1, DAXX and ATRX are entity-defining for well-differentiated NETs, whereas NECs usually have TP53 or RB1 mutations. In some cases, these mutations can be of diagnostic benefit. Genomic data have also led to a change in the classification of mixed NENs, which are now grouped into the conceptual category of 'mixed neuroendocrine–non-neuroendocrine neoplasms (MiNENs)'. Mixed adenoneuroendocrine carcinomas (MANECs), which show genomic alterations similar to those of adenocarcinomas or NECs rather than NETs, probably reflect clonal evolution within the tumours, which is a rapidly growing area of interest. The study of these mixed carcinomas may also lead to an improved understanding of other facets of clonality in tumours of the digestive system and other parts of the body. Another important change concerns the recognition that well-differentiated NETs may be high grade (G3 in the WHO grading system, defined as having a mitotic rate >20 per 2 mm2 or Ki67 >20%), but these neoplasms remain well-differentiated genetically and distinct from poorly differentiated NECs. G3 NETs were first recognised and are most common in the pancreas, but they can occur throughout the GI tract. Thus, the current WHO classification includes three grades (G1, G2 and G3) for NETs. NECs are no longer graded, as they are recognised to be uniformly high grade by definition, but continue to be separated into small-and large-cell types. There are certain terms in current day-to-day use about which many pathologists continue to disagree. The editorial board carefully considered our current understanding of carcinogenetic pathways when considering the use of specific terms and definitions. In general, the overall consensus was that established terms, definitions and criteria should not be changed unless there was strong evidence to support doing so and the proposed changes had clinical relevance. For some tumours, our understanding of the progression from normal epithelium to metastatic carcinoma remains inadequate. For example, in certain tumours the line between benign and malignant can be ambiguous, and in some cases the distinction is more definitional than biological. These are some of the many areas of tumour biology that need to be more fully investigated in the future. In the 5th edition, the terminology for precursors to invasive carcinoma in the digestive system has been standardised somewhat, although the terms 'dysplasia' and 'intra-epithelial neoplasia' are both still considered acceptable for lesions in certain anatomical locations, in acknowledgement of their ongoing clinical acceptance. For example, the term 'dysplasia' is preferred for lesions in the tubular gut, whereas 'intra-epithelial neoplasia' is preferred for those in the pancreas, gallbladder and biliary tree. For all anatomical sites, however, a two-tiered system (low- versus high-grade) is considered the standard grading system for neoplastic precursor lesions. This has replaced the three-tiered grading scheme previously used for lesions in the pancreatobiliary system.4 The term 'carcinoma in situ' continues to be strongly discouraged in clinical practice for a variety of reasons, most notably its clinical ambiguity. This term is encompassed by the category of high-grade dysplasia/intraepithelial neoplasia. Many refinements of the 4th-edition classification have been made concerning liver tumours, supported by novel molecular findings. For example, a comprehensive picture of the molecular changes that occur in common hepatocellular carcinoma has recently emerged from large-scale molecular profiling studies. Meanwhile, several rarer hepatocellular carcinoma subtypes, which together may account for 20–30% of cases, have been defined by consistent morphomolecular and clinical features, with fibrolamellar carcinoma and its diagnostic DNAJB1–PRKACA translocation being one prime example. Intrahepatic cholangiocarcinoma is now understood to be an anatomically defined entity with two different major subtypes: a large duct type, which resembles extrahepatic cholangiocarcinoma, and a small duct type, which shares significant aetiological, pathogenetic and imaging characteristics with hepatocellular carcinoma. The two subtypes have very different aetiologies, molecular alterations, growth patterns and clinical behaviours, exemplifying the conflict between anatomically and histogenetically/pathogenetically based classifications. Clinical research and study protocols will need to incorporate these findings in the near future. Also supported by molecular findings, the definition of combined hepatocellular–cholangiocarcinoma and its distinction from other entities has recently become clearer. Cholangiolocellular carcinoma is no longer considered a subtype of combined hepatocellular–cholangiocarcinoma, but rather a subtype of small duct intrahepatic cholangiocarcinoma, renamed cholangiolocarcinoma, meaning that all intrahepatic carcinomas with a ductal or tubular phenotype are now included within the category of intrahepatic cholangiocarcinoma. A classic example of morphology-based molecular profiling leading to a new classification based on a combination of biological and molecular factors is the classification of hepatocellular adenomas, which has gained a high degree of clinical relevance and has fuelled the implementation of refined morphological criteria and molecular testing in routine diagnostics. Most of the classification of pancreatic neoplasms in the 5th edition remains unchanged from the last volume. As highlighted above, precursor lesions including pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasms and mucinous cystic neoplasms are now classified into two tiers of dysplasia, based on the highest grade of dysplasia detected, rather than the three-tier system used in the last edition of the WHO classification. Intraductal oncocytic papillary neoplasm and intraductal tubulopapillary neoplasms are now separated from the other subtypes of intraductal papillary mucinous neoplasm based on their distinct genomic and morphological features. The prior entity of acinar cell cystadenoma, which has recently been demonstrated to be non-neoplastic by molecular clonality analysis, is now termed 'acinar cystic transformation of the pancreas'. Also, the entire spectrum of pancreatic neuroendocrine neoplasms is now included in this volume; previously, details concerning the individual functional types were presented in the WHO classification of tumours of the endocrine organs. Mixed tumours in several anatomical sites (e.g. oesophageal adenosquamous carcinoma and mucoepidermoid carcinoma, as well as hepatic carcinomas with mixed hepatocellular and cholangiocellular differentiation), remain subjects of some uncertainty. The relative importance of the various lineages of differentiation within these neoplasms remains unknown. It is also uncertain how these neoplasms develop and how they should be treated. These issues are a matter of debate because hard evidence is lacking, but there are improvements in the pathological criteria and classification of these neoplasms that should help to standardise the diagnostic approach and facilitate better clinical and genomic research. Each of these tumour types is grouped together in separate chapters. This ensures consistency and avoids duplication. The term 'EBV positive inflammatory follicular dendritic cell sarcoma of the digestive tract' has been adopted to replace the entity previously known as 'inflammatory pseudotumour-like fibroblastic/follicular dendritic cell tumour'. New in this book is the chapter on genetic tumour syndromes of the digestive system, the introduction to which contains a table that lists each of the major syndromes and summarises key information about the disease/phenotype, pattern of inheritance, causative gene(s) and normal function of the encoded protein(s). Common syndromes, including Lynch syndrome and familial adenomatous polyposis 1 (FAP), are covered in detail, as well as several other adenomatous polyposes defined since the last volume and the GAPPS (gastric adenocarcinoma and proximal polyposis of the stomach) syndrome, now recognised as a FAP variant, with a unique phenotype. A number of other genetic tumour predisposition syndromes that confer a raised risk of various gastrointestinal tumours are also described, including Li–Fraumeni syndrome, hereditary haemorrhagic telangiectasia, syndromes associated with gastroenteropancreatic NETs and multilocus inherited neoplasia alleles syndrome. This should be helpful to many involved in the diagnosis of such syndromes, as well as those researching the mechanisms involved. The format of the books has been updated to reflect the new edition of the classification: the move from three to two columns has allowed larger illustrations, and the use of set headings for each tumour type show very clearly where evidence is lacking. The content of this article represents the personal views of the authors and does not represent the views of the authors' employers and associated institutions. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization. I.D.N. reports that her institute benefits from research funding from the Dutch Cancer Society (KWF) and the Dutch Digestive Foundation (MLDS). No other authors report any conflicts of interest to IARC that would affect their participation in forming the classification.
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Pancreatic cancer

2016-01-30
Terumi Kamisawa , Laura D. Wood , Takao Itoi +1 more

Pancreatic cancer

2016-04-21
Jörg Kleeff , Murray Korc , Minoti V. Apte +7 more

Pancreatic cancer

2011-05-29
Audrey Vincent , Joseph M. Herman , R. Schulick +2 more
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Pancreatic cancer

2020-06-01
Jonathan D. Mizrahi , Rishi Surana , Juan W. Valle +1 more

Pancreatic Adenocarcinoma

2014-09-11
David P. Ryan , Theodore S. Hong , Nabeel Bardeesy
Cancer of the pancreas is predominantly adenocarcinoma and involves activating KRAS mutations in the large majority of cases. Surgical resection can be effective in localized disease; combination chemotherapy offers some 
 Cancer of the pancreas is predominantly adenocarcinoma and involves activating KRAS mutations in the large majority of cases. Surgical resection can be effective in localized disease; combination chemotherapy offers some palliation in advanced disease.

Pancreatic Cancer

2010-04-28
Manuel Hidalgo
Deaths from pancreatic ductal adenocarcinoma, also known as pancreatic cancer, rank fourth among cancer-related deaths in the United States, yet the causes of pancreatic cancer remain unknown. This review article 
 Deaths from pancreatic ductal adenocarcinoma, also known as pancreatic cancer, rank fourth among cancer-related deaths in the United States, yet the causes of pancreatic cancer remain unknown. This review article summarizes recent progress in the understanding and management of pancreatic cancer.

Pancreatic cancer

2004-03-01
Donghui Li , Keping Xie , Robert A. Wolff +1 more

The Future of Oncology Is Now

2025-06-25
Syed A. Ahmad , Greg C. Wilson , Sameer H. Patel | JAMA Surgery

Amylase-producing lung adenocarcinoma with an anaplastic lymphoma kinase fusion mutation: a case report

2025-06-25
Shuiqing Yang , Wenbin Li , Difeng Guo +6 more | Laboratory Medicine
Abstract Introduction Hyperamylasemia, typically a sign of digestive system disorders, especially pancreatic issues, has an unexpected link with lung cancer in some patients. This report describes such a case in 
 Abstract Introduction Hyperamylasemia, typically a sign of digestive system disorders, especially pancreatic issues, has an unexpected link with lung cancer in some patients. This report describes such a case in which hyperamylasemia was associated with ALK fusion mutant lung adenocarcinoma. Methods We identified the type of tumor through histologic analysis and pulmonary biopsy of the tumor and further identified the type of genetic mutation in the tumor using genetic testing. Subsequently, we continuously monitored the serum amylase levels and tumor size during therapy, and this process presented an analysis on the correlation between hyperamylasemia and lung adenocarcinoma while considering the response to targeted therapy. Results During the detailed research and observation process, we surprisingly discovered that the serum amylase levels throughout the entire course of therapy exhibited a remarkable parallelism with tumor size and the tumor response to targeted therapy. Discussion We suggest that serum amylase may be a tumor marker that may lead to a more effective approach to the diagnosis and treatment of related diseases.

UGT1A6 in pancreatic cancer: a promising prognostic biomarker and therapeutic target

2025-06-25
Xianping Lu , Yi Pan , Chen-jun Xie +7 more | Clinical & Translational Oncology

Artificial Intelligence–Powered Spatial Analysis of Immune Phenotypes in Resected Pancreatic Cancer

2025-06-25
Hye Min Kim , Jin Ho Choi , Yoojoo Lim +7 more | JAMA Surgery
Importance Although tumor-infiltrating lymphocytes (TILs) have been implicated as prognostic biomarkers across various malignancies, the clinical application remains challenging. This study evaluated the applicability of artificial intelligence (AI)–powered spatial mapping 
 Importance Although tumor-infiltrating lymphocytes (TILs) have been implicated as prognostic biomarkers across various malignancies, the clinical application remains challenging. This study evaluated the applicability of artificial intelligence (AI)–powered spatial mapping of TIL density for prognostic assessment in resected pancreatic ductal adenocarcinoma (PDAC). Objective To evaluate the prognostic significance of AI-powered spatial TIL analysis in resected PDAC and its clinical applicability. Design, Setting, and Participants This cohort study included patients with PDAC who underwent up-front R0 resection at a tertiary referral center between January 2017 and December 2020. Whole-slide images of retrospectively enrolled patients with PDAC and up-front R0 resection were analyzed. An AI-powered whole-slide image analyzer was used for spatial TIL quantification, segmentation of tumor and stroma, and immune phenotype classification as immune-inflamed phenotype, immune-excluded phenotype, or immune-desert phenotype. Study data were analyzed from January 2017 to August 2023. Exposure Use of AI-powered spatial analysis of the tumor microenvironment in resected PDACs. Main Outcomes and Measures Tumor microenvironment–related risk factors and their associations with overall survival (OS) and recurrence-free survival (RFS) outcomes were identified. Results Among 304 patients, the mean (SD) age was 66.8 (9.4) years with 171 male patients (56.3%), and preoperative clinical stages I and II were represented by 54.3% patients (165 of 304) and 45.7% patients (139 of 304), respectively. The TILs in the tumor microenvironment were predominantly concentrated in the stroma, and the median intratumoral TIL and stromal TIL densities were 100.64/mm 2 (IQR, 53.25-121.39/mm 2 ) and 734.88/mm 2 (IQR, 443.10-911.16/mm 2 ), respectively. Overall, 9.9% of tumors (30 of 304) were immune inflamed, 85.2% (259 of 304) were immune excluded, and 4.9% (15 of 304) were immune desert. The immune-inflamed phenotype was associated with the most prolonged OS (median not reached; P &amp;amp;lt; .001) and RFS (median not reached; P = .001), followed by immune-excluded phenotype and immune-desert phenotype. High intratumoral TIL density was associated with longer OS (median, 52.47 months; 95% CI, 41.98-62.96; P = .004) and RFS (median, 21.67 months; 95% CI, 14.43-28.91; P = .02). A combined analysis of the pathologic stage with immune phenotype predicted better survival of stage II PDAC stratified as immune-inflamed phenotype than stage I PDAC stratified as non–immune-inflamed phenotype. Conclusions and Relevance Results of this cohort study suggest that the use of AI has markedly condensed the labor-intensive process of TIL assessment, potentially rendering the process more feasible and practical in clinical application. Importantly, the IP may be one of the most important prognostic biomarkers in resected PDACs.

Letter to the Editor: A commentary on “Clinical efficacy and chemoresistance analysis of precision neoadjuvant chemotherapy for borderline resectable pancreatic cancer: a prospective, single-arm pilot study”

2025-06-24
Qinglong Wang , Gang Qin | International Journal of Surgery

A Step-By-Step Guide for Robotic Blumgart Pancreaticojejunostomy

2025-06-24
Siyuan Qian , Jeison Carrillo-Peña , Víctor Domínguez Prieto +4 more | Journal of Clinical Medicine
Background: In recent years, the use of minimally invasive approaches in pancreatic surgery has progressively increased. One of the key components of pancreaticoduodenectomy is the creation of a pancreato-enteric anastomosis, 
 Background: In recent years, the use of minimally invasive approaches in pancreatic surgery has progressively increased. One of the key components of pancreaticoduodenectomy is the creation of a pancreato-enteric anastomosis, due to the high risk of postoperative complications, particularly the development of postoperative pancreatic fistula. Among the types of anastomoses, the Blumgart technique has gained popularity due to its ease of reproducibility. Methods: In this guide, we summarize and systematize step by step how to perform a feasible, reproductible and safe robotic Blumgart pancreaticojejunostomy, providing some instructions for its successful completion. Results: Despite the heterogeneity of the published data, duct-to-mucosa Blumgart anastomosis seems to be superior in terms of clinically relevant postoperative pancreatic fistula rates compared with other types of pancreato-enteric anastomosis. The advantages of robotic surgery, such as improved precision, greater control, and enhanced visualization, make robotic Blumgart anastomosis a safe, practical, and reproducible technique in the context of robotic pancreaticoduodenectomy. Conclusions: Robotic Blumgart pancreaticojejunostomy is a safe and feasible technique for pancreato-enteric anastomosis following pancreaticoduodenectomy when surgical technique is systematized step by step.

Silent Yet Striking: Medullary Carcinoma Behind an Intestinal Obstruction

2025-06-24
Nasim Salimiaghdam , Ahmed Mustafa , Irene O Pokuaa +2 more | Cureus

O PAPEL DO MICROAMBIENTE TUMORAL NA PROGRESSÃO DO ADENOCARCINOMA GÁSTRICO

2025-06-24
ISABELA REIMANN AGNE , Leonardo Neves , Fernando Kojo Matsuura | Editora Pasteur eBooks

The VIPR-1 trial (Visualizing Ischemia in the Pancreatic Remnant): Assessing the role of intraoperative indocyanine green perfusion in predicting postoperative pancreatic leaks and fistulas: Protocol for a phase II clinical trial

2025-06-24
Gustavo Salgado‐Garza , Annika Willy , Flavio G. Rocha +3 more | PLoS ONE
Surgery of the pancreas has come a long way since its inception; however, postoperative morbidity is still high. Pancreatic leaks and fistulas are common complications in patients undergoing surgery to 
 Surgery of the pancreas has come a long way since its inception; however, postoperative morbidity is still high. Pancreatic leaks and fistulas are common complications in patients undergoing surgery to remove the pancreas. Fistulas delay subsequent oncological care after surgery and prolong the hospital stay. Hypoperfusion of the pancreas has been proposed as one factor leading to fistulas. Indocyanine green (ICG) injection allows the surgeon to evaluate blood perfusion to tissue in real-time. This protocol describes a trial that aims to assess the effectiveness of intraoperative ICG metrics of the cut edge of the remnant pancreas to predict postoperative fistulas. A single group will participate in an observational, surgeon-blinded, phase II trial. ICG measurements of the cut edge of the pancreas will be recorded before reconstruction. International Study Group on Pancreatic Surgery criteria for pancreatic fistula will be used to define leaks and fistulas. The study objective is to analyze the correlation between ICG measurements and the development or absence of both biochemical leak and clinically relevant fistula formation. Currently, limited objective intraoperative predictors exist for predicting postoperative fistulas. Having a reliable predictive tool could decrease the healthcare burden posed by fistulas. The findings of this trial will provide conclusions on the usefulness of ICG measurements in predicting postoperative pancreatic fistulas and leaks. This clinical trial is registered in ClinicalTrials.gov with the ID NCT06084013. The current protocol version is v1.1.

Letter to editor: virtual 3D models, augmented reality systems and virtual laparoscopic simulations in complicated pancreatic surgeries: state of art, future perspectives, and challenges

2025-06-24
Jiaqi Yao , Chao Wu , Chi Ma | International Journal of Surgery

Efficacy of Probiotics as Adjuvant Therapy in Cancer Patients Receiving ICIs: A Systematic Review

2025-06-24
Yan Guo , Luxi Zhang , Kei Tomihara | International Journal of Oral and Maxillofacial Surgery

Anaplastic carcinoma of the pancreas derived from an intraductal papillary mucinous neoplasm: a case report

2025-06-24
Yoko Kawano , Teijiro Hirashita , Hiroyoshi Ichihara +6 more | Clinical Journal of Gastroenterology

Exploring the Causal Relationship Between Pancreatic Cancer and Gut Microbiota: A Bidirectional Mendelian Randomization Study

2025-06-23
Yutong Zhao , Weibin Wang | Journal of Pancreatology
Objective: Observational studies have suggested a correlation between gut microbiota and pancreatic cancer, but the causal relationship remains uncertain. This study aims to further investigate potential links between 207 gut 
 Objective: Observational studies have suggested a correlation between gut microbiota and pancreatic cancer, but the causal relationship remains uncertain. This study aims to further investigate potential links between 207 gut microbiota and PC. Methods: We used two-sample Mendelian randomization (MR) analysis to explore the causal relationships between gut microbiota and PC. The study analyzed genome-wide association study (GWAS) data from European populations, covering 207 gut microbiota (n = 7,738) and PC (n = 314,924). Results: Our research identified eight microbial species that have a causal link with PC. Parabacteroides merdae (p=0.032, OR=0.611, 95% CI: 0.389-0.959), Ruminococcus lactaris (p=0.030, OR=0.571, 95% CI: 0.344-0.948), and Veillonella (unclassified) (p=0.038, OR=0.781, 95% CI: 0.618-0.987) were negatively associated with the risk of pancreatic cancer. In contrast, Bacteroides coprocola (p=0.008, OR=1.464, 95% CI: 1.104-1.942), Bacteroides finegoldii (p=0.030, OR=1.253, 95% CI: 1.022-1.535), Bacteroides fragilis (p=0.033, OR=1.301, 95% CI: 1.021-1.657), Prevotella copri (p=0.003, OR=1.654, 95% CI: 1.188-2.301), and Holdemania (unclassified) (p=0.007, OR=1.428, 95% CI: 1.105-1.846) were identified as potential risk factors for pancreatic cancer. Additionally, during the progression of PC, nine types of gut microbiota may be affected. PC may decrease the levels of Alistipes senegalensis (p=0.041, OR=0.948, 95% CI: 0.901-0.998), Eubacterium ramulus (p=0.034, OR=0.928, 95% CI: 0.867-0.994), Eubacterium ventriosum (p=0.027, OR=0.913, 95% CI: 0.841-0.990), Ruminococcus lactaris (p=0.004, OR=0.910, 95% CI: 0.853-0.971), Eubacterium biforme (p=0.031, OR=0.904, 95% CI: 0.825-0.991), Bilophila (unclassified) (p=0.023, OR=0.944, 95% CI: 0.898-0.992), and Akkermansia muciniphila (p=0.022, OR=0.940, 95% CI: 0.892-0.991). Conversely, PC may increase the levels of Parabacteroides merdae (p=0.019, OR=1.066, 95% CI: 1.011-1.124) and Lachnospiraceae bacterium 1_1_57FAA (p=0.028, OR=1.153, 95% CI: 1.015-1.309). Conclusion: We identified eight gut microbiota species causally associated with PC. Three were negatively associated with the risk of PC, while five may contribute to its development. The progression of PC may decrease the levels of seven gut microbiota species and increase the levels of two. This study highlights the potential of gut microbiota for early diagnosis and treatment of PC. Further research is needed to determine whether these findings could serve as potential targets for preventing or treating PC.

Survival Impact of Adjuvant Chemoradiotherapy in Resected Pancreatic Cancer

2025-06-23
EyyĂŒp Çavdar , Kubilay Karaboyun , Yakup Ä°riağaç +3 more | Namık Kemal Tıp Dergisi

Clinical benefits of deep learning-assisted ultrasound in predicting lymph node metastasis in pancreatic cancer patients

2025-06-23
Dong‐yue Wen , Jiamin Chen , Zhiping Tang +5 more | Future Oncology
This study aimed to develop and validate a deep learning radiomics nomogram (DLRN) derived from ultrasound images to improve predictive accuracy for lymph node metastasis (LNM) in pancreatic cancer (PC) 
 This study aimed to develop and validate a deep learning radiomics nomogram (DLRN) derived from ultrasound images to improve predictive accuracy for lymph node metastasis (LNM) in pancreatic cancer (PC) patients. A retrospective analysis of 249 histopathologically confirmed PC cases, including 78 with LNM, was conducted, with an 8:2 division into training and testing cohorts. Eight transfer learning models and a baseline logistic regression model incorporating handcrafted radiomic and clinicopathological features were developed to evaluate predictive performance. Diagnostic effectiveness was assessed for junior and senior ultrasound physicians, both with and without DLRN assistance. InceptionV3 showed the highest performance among DL models (AUC = 0.844), while the DLRN model, integrating deep learning and radiomic features, demonstrated superior accuracy (AUC = 0.909), robust calibration, and significant clinical utility per decision curve analysis. DLRN assistance notably enhanced diagnostic performance, with AUC improvements of 0.238 (p = 0.006) for junior and 0.152 (p = 0.085) for senior physicians. The ultrasound-based DLRN model exhibits strong predictive capability for LNM in PC, offering a valuable decision-support tool that bolsters diagnostic accuracy, especially among less experienced clinicians, thereby supporting more tailored therapeutic strategies for PC patients.

Cell-specific nanoengineering strategy to disrupt tolerogenic signaling from myeloid-derived suppressor cells and invigorate antitumor immunity in pancreatic cancer

2025-06-23
Nilesh Deshpande , Anna Bianchi , Haleh Amirian +7 more | Cancer Immunology Immunotherapy
Pancreatic ductal adenocarcinoma (PDAC) is characterized by intratumoral abundance of neutrophilic/polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) which exert anti-T-cell functions through multiple mechanisms, especially JAK2/STAT3-regulated arginase activity. To overcome limitations of 
 Pancreatic ductal adenocarcinoma (PDAC) is characterized by intratumoral abundance of neutrophilic/polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) which exert anti-T-cell functions through multiple mechanisms, especially JAK2/STAT3-regulated arginase activity. To overcome limitations of systemic inhibition of PMN-MDSCs in cancer-bearing patients such as neutropenia and compensatory myelopoietic adaptations, we developed a nanoengineering strategy to disrupt cell-specific signaling exclusively in PMN-MDSCs without compromising viability or provoking neutropenia. Single-cell RNA sequencing in human/murine PDAC, and flow cytometry in peripheral blood cells from treatment-naïve PDAC patients, nominated surface receptor CXCR2 as a PMN-MDSC-exclusive target. We chemically modified a small-molecule CXCR2 inhibitor AZD5069 by conjugating it with polyethylene glycol (PEG) to enhance aqueous solubility. This AZD5069-PEG construct was then chemically grafted onto amphiphilic polysaccharide derivatives to engineer CXCR2-homing nanoparticles (CXCR2-NP). Cy5.5 dye-loaded CXCR2-NPs showed near-exclusive uptake in PMN-MDSCs compared with KrasLSL.G12D/+;p53R172H/+;Pdx1Cre/+ (KPC) PDAC tumor cells, KPC cancer-associated fibroblasts, macrophages, and dendritic cells. Encapsulation of JAK2/STAT3i Ruxolitinib (CXCR2-NPRuxo) resulted in more efficient and durable attenuation in STAT3-regulated arginase activity from PMN-MDSCs as well as robust induction of cytolytic T-cell activity compared with free Ruxolitinib in vitro and in orthotopic tumor cell-CAF co-injection models in vivo. Treatment of orthotopic tumor-bearing KPC mice with CXCR2-NPRuxo reduced tumor burden compared with vehicle, free Ruxolitinib, or non-drug-loaded CXCR2-NP treatments, without causing appreciable neutropenia. Taken together, cell-specific delivery of payloads via CXCR2-homing immunonanoparticles represents a novel strategy to disrupt MDSC-mediated immunosuppression and invigorate antitumor immunity in PDAC.

Addressing Pancreatic Cancer Disparities in Oregon’s Native American Population via Tribally Responsive Research Systems with The Confederated Tribes of Warm Springs

2025-06-23
Jared Delaney , L James , Paige E. Farris +5 more | Research Square (Research Square)
<title>Abstract</title> Purpose In Oregon, the incidence of Pancreatic Cancer is 2-times higher among American Indian and Alaska Native (AIAN) communities than among the rest of the population nationwide. We wanted 
 <title>Abstract</title> Purpose In Oregon, the incidence of Pancreatic Cancer is 2-times higher among American Indian and Alaska Native (AIAN) communities than among the rest of the population nationwide. We wanted to know if the previously validated Research in Oregon’s Communities Review System (ROCRS) could be adapted to investigate this disparity while upholding tribal sovereignty. Methods We partnered with The Confederated Tribes of Warm Springs with the goal of adapting the ROCR System to address the pancreatic cancer disparity with a culturally responsive approach. One-on-one interviews with community members were conducted at the annual Pi-Ume-Sha Health Fair in 2023. Cancer-related data was requested from the Northwest Portland Area Indian Health Board. Barriers to healthcare access were identified and categorized using PESTLE analysis. A Tribal liaison combined this analysis with cancer-related data to create a cultural landscape. This was done in accordance with the ROCRS system. Results This culturally responsive approach fosters trust and engagement in pancreatic cancer research and creates actionable insights for researchers while maintaining tribal sovereignty. Conclusion The success of this model demonstrates the potential of tribally tailored research systems to improve participation and long-term collaborations with this underrepresented population.

Pancreaticojejunostomy Versus Neoprene-based Pancreatic Duct Occlusion in Pancreaticoduodenectomy for Patients at Intermediate-high Risk of Post-operative Pancreatic Fistula

2025-06-23
Carlo Sposito , Michele Mazzola , Isabella Pezzoli +7 more | Annals of Surgery
To compare the short-term outcomes of pancreaticojejunostomy (PJ) and pancreatic duct occlusion (PDO) in patients at intermediate-high risk of postoperative pancreatic fistula (POPF). Postoperative pancreatic fistula (POPF) is the most 
 To compare the short-term outcomes of pancreaticojejunostomy (PJ) and pancreatic duct occlusion (PDO) in patients at intermediate-high risk of postoperative pancreatic fistula (POPF). Postoperative pancreatic fistula (POPF) is the most fearsome complication of pancreaticoduodenectomy (PD). Patients undergoing PD with intermediate-high fistula risk scores (FRS) at two tertiary centers between 2012 and 2022 were included. To reduce biases between the groups, entropy balance and inverse probability of treatment weighting (EB-IPTW) were used. A total of 302 patients were included (224, 74.2% PJs and 78, 25.8% PDOs). After EB-IPTW, two weighted pseudo-populations of 224 patients were obtained. Major complications, POPF, reoperations and post-operative mortality were similar. Patients undergoing PDO had lower rates of grade C POPF (3.3% vs. 6.7%), delayed gastric emptying (15.7% vs. 24.6%, P=0.02), intra-abdominal collections (7.3% vs. 20.5%, P<0.001) and 90-day readmissions (2.7% vs. 9.4%, P=0.005). In subgroup analysis, PDO reduced POPF in patients with high FRS and blood loss >400 mL, while PJ was more effective in intermediate FRS class, duct diameter ≄2 mm, blood loss <400 mL, ASA class >II, younger patients and BMI <25 kg/m2. In the unbalanced cohorts, completion pancreatectomy was required in 10 (4.5%) patients after PJ and in 1 (1.2%) after PDO. The main perioperative outcomes of PJ and PDO after PD in intermediate-high risk FRS patients are similar. PDO decreases the rate of POPF in patients with high-risk FRS, and reduces the need of completion pancreatectomy in case of reoperation.

Artery-First Approach During Minimally Invasive Pancreatoduodenectomy for Pancreatic Cancer: Outcomes from a Single Center and Comparison Between Laparoscopic and Robotic Approaches

2025-06-23
Michele Mazzola , Michele Paterno , Alessandro Giani +6 more | Cancers
Background: Despite benefits during open pancreatoduodenectomy (PD), the artery-first approach (AFA) during minimally invasive PD (MIPD) has been poorly investigated. Methods: Data of consecutive patients undergoing MIPD (both laparoscopic (LPD) 
 Background: Despite benefits during open pancreatoduodenectomy (PD), the artery-first approach (AFA) during minimally invasive PD (MIPD) has been poorly investigated. Methods: Data of consecutive patients undergoing MIPD (both laparoscopic (LPD) and robotic (RPD)) from 2020 to 2024 for pancreatic cancer (PC) were prospectively collected and retrospectively analyzed, comparing the surgical and oncological outcomes of LPD with right AFA and RPD with posterior AFA. The rate of ineffective AFA (IAFA), defined in the case of excessive resection time, estimated blood loss, or conversion to laparotomy, was also investigated. Results: 71 patients undergoing MIPD were selected (32 LPD and 39 RPD). Baseline patients’ characteristics only differed for a higher rate of neoadjuvant treatment in LPD and RPD groups, respectively (23.1% vs. 0%, p = 0.0036). No patients underwent conversion. R0 resection was obtained in 74.6% of patients. No difference between the groups was found regarding intraoperative, postoperative, and oncological outcomes except for a greater number of lymph nodes harvested in RPD (24 vs. 17, p = 0.023). IAFA was observed in 12.7% of patients, without difference between the groups (9.4 vs. 15.4%, p = 0.499, in LPD and RPD, respectively). Conclusions: MIPD with AFA was feasible and safe in patients affected by PC. RPD using posterior AFA had a higher number of lymph nodes retrieved when compared to LPD using right AFA. RPD has provided subjective advantages for the surgeon in terms of handling, safety, and reproducibility, although these have not translated into better outcomes.

Association Between Metformin Use and Mortality Among Individuals With Non-Small Cell Lung Cancer Receiving Immune Checkpoint Inhibitors

2025-06-23
Xinyi Sun , James Heyward , Joseph C. Murray +2 more | Journal of Immunotherapy
Metformin has the potential to synergistically enhance the effect of immune checkpoint inhibitors (ICI) in nonsmall cell lung cancer (NSCLC). We evaluated the association between metformin use before ICI initiation 
 Metformin has the potential to synergistically enhance the effect of immune checkpoint inhibitors (ICI) in nonsmall cell lung cancer (NSCLC). We evaluated the association between metformin use before ICI initiation and cancer-specific and all-cause mortality among NSCLC patients. We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare data (2013-2019), including NSCLC patients with type 2 diabetes who newly initiated ICI therapy and had prior antidiabetic medication use. The exposure was metformin monotherapy versus sulfonylurea and/or dipeptidyl peptidase-4 (DPP-4) inhibitors. The primary outcome was cancer-specific mortality, and the secondary outcome was all-cause mortality. We used stabilized inverse probability of treatment weighting (sIPTW) to adjust for confounders. Fine-Gray competing risk model estimated cancer-specific mortality, while Cox proportional hazards model evaluated all-cause mortality. We included 1123 metformin users and 362 sulfonylurea/DPP-4 users. Although baseline characteristics differed, groups were well balanced after weighting. The adjusted incidence rate (aIR) of cancer-specific mortality was 82 versus 81 (aIR difference=1, 95% CI: -13 to 16), and all-cause mortality was 71 versus 67 (aIR difference=4, 95% CI: -6 to 15) per 100 person-years for metformin and sulfonylurea/DPP-4 users, respectively. Metformin use was not significantly associated with cancer-specific mortality (adjusted hazard ratio (aHR)=1.08, 95% CI: 0.88-1.33) and all-cause mortality (aHR=1.07, 95% CI: 0.90-1.26). In this large, diverse cohort of individuals with NSCLC using ICI, there was no statistically significant association between metformin use and cancer-specific or all-cause mortality.

ASO Author Reflections: Reasonable Doubt: The Case for Somatostatin Analogs in Pancreas Surgery Remains Unsettled

2025-06-23
Kristin E. Goodsell , Jonathan G. Sham | Annals of Surgical Oncology

Robot-assisted and Laparoscopic Extended Left Pancreatectomy

2025-06-23
C.L. Bruna , Tess van Ramshorst , Jony van Hilst +7 more | Annals of Surgery
To compare postoperative outcomes after extended robot-assisted left pancreatectomy (e-RLP) and extended laparoscopic left pancreatectomy (e-LLP). The implementation of RLP is increasing worldwide with expanding indications, resulting in more extended 
 To compare postoperative outcomes after extended robot-assisted left pancreatectomy (e-RLP) and extended laparoscopic left pancreatectomy (e-LLP). The implementation of RLP is increasing worldwide with expanding indications, resulting in more extended resections. However, the use of e-RLP has not been investigated before. International study including consecutive patients after e-RLP and e-LLP for all indications in 19 European countries (2012-2022). Extended resection was defined according to the ISGPS definition. Propensity score matching (PSM) was performed in a 1:1 ratio with a caliper width of 0.1. Primary endpoint was major morbidity (Clavien-Dindo grade ≄III complications). Overall, 514 patients were included from 72 centers (152 e-RLPs; 362 e-LLPs). Before PSM, e-RLP patients had more tail tumors (69.4% vs 50.0%, P=0.001), vascular involvement (30.3% vs 16.3%, P<0.001) and >2 additional organ resections (28.5% vs 10.7%, P<0.001), with comparable major morbidity rates (27.0% vs 27.0%, P=0.991) and a lower conversion rate (15.1% vs 23.5%, P=0.033), compared to e-LLP. After PSM, 119 e-RLP patients were matched to 119 e-LLP patients. No significant differences were observed in major morbidity (23.5% vs 26.5%, P=0.599), blood loss (200 vs 150 mL, P=0.835), conversion rate (16.0% vs 20.0%, P=0.422), 30-day/in-hospital mortality (1.7% vs 3.4%, P=0.408), and hospital stay (median 7 vs 7 days, P=0.906). E-RLP had longer operative times (median 277 vs 228 min, P<0.001). This pan-European cohort study found no significant differences in the outcomes among matched patients undergoing e-RLP and e-LLP, although e-RLP was associated with a longer operative time. The robot-assisted approach is used for more extensive resections with a comparable major morbidity rate compared to laparoscopy.

[Epidemiological characteristics of pancreatic cancer in China and worldwide].

2025-06-23
Jianbo Wang , Lu Ding , Yingzhao Yan +5 more | PubMed
Objective: To analyze pancreatic cancer incidence and mortality data in China and worldwide and to provide data for pancreatic cancer prevention and control efforts. Methods: Data of pancreatic cancer incidence 
 Objective: To analyze pancreatic cancer incidence and mortality data in China and worldwide and to provide data for pancreatic cancer prevention and control efforts. Methods: Data of pancreatic cancer incidence and mortality rates, along with historical and predictive data, were obtained from the GLOBOCAN 2022 database. Epidemiological characteristics of pancreatic cancer was analyzed by region, sex, age and Human Development Index (HDI). Spearman's correlation coefficient test was used to assess the relationship between HDI and age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR). Results: In 2022, the global number of new cases and deaths of pancreatic cancer will be 511 thousand and 467 thousand, respectively, with an ASIR and ASMR of 4.7/105 and 4.2/105, respectively. North America and Europe had the highest pancreatic cancer incidence and mortality rates of 8.5/105 and 7.3/105, respectively. Global ASIR and ASMR in men were both 1.4 times higher than those in women. HDI levels were positively correlated with ASIR (r=0.79, P0.001) and ASMR (r=0.78, P0.001) of pancreatic cancer in all regions. The number of pancreatic cancer cases and deaths in China were 119 thousand and 106 thousand, respectively, while the ASIR and ASMR of pancreatic cancer were 4.4/105 and 3.9/105, respectively. Both ASIR and ASMR in men were both 1.5 times higher than those in women in China. The number of pancreatic cancer incidence and death cases in China in 2050 is predicted to be 216 thousand and 204 thousand cases, with an increase of 81.5% and 92.5% compared with 2022, respectively. Conclusions: The disease burden of pancreatic cancer varies significantly among different regions, genders and ages. Pancreatic cancer incidence and mortality are positively correlated with HDI. The incidence and mortality rates of pancreatic cancer in China are close to the global average, but the number of new cases and deaths is high. Prevention and control should be strengthened to improve the survival of pancreatic cancer patients.

Type 2 diabetes alters quiescent pancreatic stellate cells to tumor-prone state

2025-06-22
Yutaro Hara , Hiroki Mizukami , Takahiro Yamada +7 more | JCI Insight
Pancreatic stellate cells (PSCs) are the origin of cancer-associated fibroblasts. Type 2 diabetes mellitus (T2D) may promote pancreatic ductal adenocarcinoma (PDAC), eliciting changes in the quiescent PSC (qPSC) population from 
 Pancreatic stellate cells (PSCs) are the origin of cancer-associated fibroblasts. Type 2 diabetes mellitus (T2D) may promote pancreatic ductal adenocarcinoma (PDAC), eliciting changes in the quiescent PSC (qPSC) population from the precancerous stage. However, the details are unknown. We evaluated the subpopulations of qPSCs and the impact of T2D. PSCs isolated from 8-week-old C57BL/6J mice and diabetic db/db mice were analyzed by single-cell RNA-seq. Sorted qPSCs and PDAC cells were transplanted into allogenic mice. The isolated qPSCs were broadly classified into mesothelial cell and pancreatic fibroblast (Paf) populations by single-cell RNA-seq. Pafs were subclassified into inflammatory Pafs, myofibroblastic Pafs (myPafs) and a small population named tumor immunity- and angiogenesis-promoting Pafs (tapPafs), expressing Cxcl13. In the subcutaneous transplantation model, the tumors transplanted with myPafs were significantly larger than the tumors transplanted with tapPafs. An increase in myPafs and a decrease in tapPafs were observed from the precancerous stage in human T2D, indicating the effects of tumor progression. This study revealed the subpopulation changes in qPSCs in T2D. A therapy that increases the number of tapPafs could be a therapeutic option for patients with PDAC and T2D and even those in a precancerous stage of T2D.

Comparison of Pancreatic Fistula Between Robotic‐Assisted and Open Pancreatoduodenectomy: A Comprehensive Evaluation Using an Alternative Fistula Risk Score

2025-06-21
Charnwit Assawasirisin , Youngmin Han , Hye‐Sol Jung +5 more | Journal of Hepato-Biliary-Pancreatic Sciences
ABSTRACT Background Robotic‐assisted pancreatoduodenectomy (RPD) offers ergonomic advantages, yet its effect on pancreatic fistula risk remains unclear. This study evaluated RPD safety using the alternative fistula risk score (aFRS). Methods 
 ABSTRACT Background Robotic‐assisted pancreatoduodenectomy (RPD) offers ergonomic advantages, yet its effect on pancreatic fistula risk remains unclear. This study evaluated RPD safety using the alternative fistula risk score (aFRS). Methods We retrospectively reviewed the pancreatoduodenectomy database at Seoul National University Hospital (2014–2023), comparing RPD with open pancreatoduodenectomy (OPD) in a 1:1 aFRS probability‐matched analysis. Baseline characteristics and outcomes were compared overall and by aFRS risk groups. Results In the matched cohort, RPD patients had a similar BMI but a higher incidence of soft pancreatic texture, smaller ducts, and increased aFRS probability compared to OPD. Overall, clinically relevant postoperative pancreatic fistula (CR‐POPF) rates were similar (11% vs. 10%, p = 0.84). However, RPD had lower rates of delayed gastric emptying (3.1% vs. 5.4%, p = 0.024) and wound complications (1.9% vs. 5.5%, p &lt; 0.001). Notably, in the high‐risk aFRS group, RPD demonstrated significantly lower CR‐POPF rates both before (12% vs. 18%, p = 0.049) and after matching (11% vs. 17%, p = 0.042). Conclusion RPD is a safe and feasible approach, offering particular benefits in reducing CR‐POPF among high‐risk patients.

Efficacy of losartan plus modified FOLFIRINOX versus modified FOLFIRINOX in advanced pancreatic cancers: A randomized clinical trial (AFPAC Study)

2025-06-21
Anant Ramaswamy , Prabhat Bhargava , Vikram Gota +7 more | Cancer
Abstract Background The addition of angiotensin receptor blockers like losartan (L) has been shown to improve outcomes in small prospective studies of pancreatic ductal adenocarcinomas (PDAC). Methods Patients diagnosed with 
 Abstract Background The addition of angiotensin receptor blockers like losartan (L) has been shown to improve outcomes in small prospective studies of pancreatic ductal adenocarcinomas (PDAC). Methods Patients diagnosed with treatment‐naive locally advanced/metastatic PDAC with Eastern Cooperative Oncology Group performance status 0‐1 and adequate end‐ organ function were randomly assigned (1:1) to either chemotherapy (mFOLFIRINOX or mFOLFIRINOX plus oral losartan 50 mg per day). The current unplanned analysis was conducted to identify an early signal of efficacy. Plasma TGF‐ÎČ levels were measured at baseline, post cycle 1, and post cycle 4 in both arms. Results With a median follow‐up of 16.8 months, a total of 88 patients were randomized in the mFOLFIRINOX and mFOLFIRINOX‐L arms (44 patients per arm). The number of deaths at 6 months, 6‐month overall survival (OS), and median OS was 12, 72.7% (95% confidence interval [CI], 59.3–86.1), and 10.4 months versus 11, 73.2% (95% CI, 59.4–87), and 9.1 months, respectively, with a hazard ratio of 0.76 (95% CI, 0.47–1.22, p = .392). There were no differences in response rates (22% vs. 23%) between the mFOLFIRINOX and FOLFIRINOX‐L arms, respectively. Nine patients (22%; n = 41) required temporary cessation of losartan due to accompanying chemotherapy‐related adverse events. The trend of plasma TGF‐ÎČ levels across time points was not significantly different between the two arms (ANOVA p &gt; .05). Conclusions The addition of losartan to mFOLFIRINOX in the AFPAC study did not provide an early signal of efficacy in improving progression‐free survival in advanced PDAC. The trial will not proceed to full accrual of phase 3 design.

Overcoming the Challenges of Uncinate Process Oncologic Management: The Left-Side Approach in Minimally Invasive Pancreatoduodenectomy: Step-by-Step Technique and Video

2025-06-21
Alessia Fassari , Vito De Blasi , A. Amariutei +1 more | Annals of Surgical Oncology

AI Enhanced Medical Image Analysis for Early Pancreatic Cancer Detection

2025-06-21
N Nujha | International Journal for Research in Applied Science and Engineering Technology
Pancreatic cancer is among the most lethal malignancies worldwide, primarily due to its frequent diagnosis at advanced stages, which contributes to a notably low five-year survival rate. The organ’s deep 
 Pancreatic cancer is among the most lethal malignancies worldwide, primarily due to its frequent diagnosis at advanced stages, which contributes to a notably low five-year survival rate. The organ’s deep anatomical position within the abdominal cavity, often concealed by surrounding structures, poses significant challenges for early clinical detection through conventional examinations. However, early identification is achievable with advanced medical imaging modalities like computed tomography (CT) and magnetic resonance imaging (MRI). Recent developments in Computer-Aided Diagnosis (CAD) systems have demonstrated encouraging potential in enhancing the detection of pancreatic cancer at an earlier stage. This study introduces a comprehensive framework that extends current CAD methodologies by incorporating five integrated components: image preprocessing, segmentation, feature extraction, classification, and explainable artificial intelligence (XAI). The preprocessing stage enhances image clarity using color transformation and isotropic diffusion filtering. For segmentation, a U-Net-based neural architecture effectively delineates tumor regions. Subsequent feature extraction, performed using a ResNet-50 model, captures key image attributes such as contrast, correlation, and dissimilarity. A hybrid classification model, combining Deep Convolutional Neural Networks (DCNN) and Deep Belief Networks (DBN), is employed to distinguish between malignant and benign tissues. To promote transparency and clinical acceptance, interpretability tools like Grad-CAM and SHAP are integrated, offering visual and statistical insights into model decision-making

Prevalence and clinical relavance of germline mutations in Chinese patients with pancreatic cancer

2025-06-21
Yu Jiang , Dan Li , Yang Liu +6 more | Cell Communication and Signaling
The prevalence and clinical significance of germline sequence variations in unselected Chinese pancreatic cancer (PC) patients remain underexplored. This retrospective study analyzed PC patients (not selected for age or family 
 The prevalence and clinical significance of germline sequence variations in unselected Chinese pancreatic cancer (PC) patients remain underexplored. This retrospective study analyzed PC patients (not selected for age or family history) who underwent germline cancer predisposition gene analysis from January 2019 to December 2023 at Ruijin Hospital. Comparative data were sourced from The Genome Aggregation Database (gnomAD) and the China Metabolic Analytics Project (ChinaMAP) database. Germline P/LP variants were classified using MSK's Precision Oncology Knowledge Base, and their clinical relevance and potential for genotype-directed therapy were evaluated. Sequencing of 1812 unselected Chinese PC cases (1088 [60.0%] male; mean [SD] age, 65.3 [9.5] years) identified 185 pathogenic and Likely pathogenic germline variants (P/LP GVs) in 174 patients (9.3%, 95% CI 8.0%-10.7%), with 43.1% affecting known pancreatic cancer susceptibility genes. Patients with P/LP GVs were diagnosed 2.68 years younger (p < 0.001) than those without. Besides the known PC predisposition genes, DNMT3A emerge as novel potential susceptibility genes for PC. OncoKB classification showed 54.0% had P/LP GVs with therapeutic implications, occurring in 94 out of 1,812 (5.2%) Chinese PC patients. Collectively, P/LP GVs in homologous recombination genes constituted 95.7% (n = 90) of all therapeutically actionable GVs. After adjustment, patients with P/LP GVs exhibited significantly improved overall survival (OS) than those without (HR = 0.7107, 95% CI: 0.5390-0.9373, p = 0.0156). Among patients with P/LP GVs, 119 had de novo metastases. Those with OncoKB level 1 variants had better OS than those without. Additionally, patients received genotype directed chemo or targeted therapies had much better improved survival. In this cohort, 5.2% of PC patients possessed therapeutically relevant P/LPGVs. Germline testing may provide prognostic benefits and is crucial for therapy selection, particularly in metastatic PC patients.

Fatal Duodenal Ulcer Hemorrhage in a Post-Operative Patient of Proximal Femur Fracture Undergoing Carbon Ion Radiotherapy for Locally Advanced Pancreatic Carcinoma: A Case Report

2025-06-21
Hiroki Iida , Mikako Suzuki , Hiroya Mizokami +2 more | Cureus

Comparative Analysis of Open, Laparoscopic, and Robotic Pancreaticoduodenectomy: A Systematic Review of Randomized Controlled Trials

2025-06-21
Valentina Valle , Paraskevas Pakataridis , Tiziana Marchese +7 more | Medicina
Background and Objectives: Various publications have compared outcomes among open (OPDs), laparoscopic (LPDs), and robotic pancreaticoduodenectomies (RPDs); however, the number of randomized controlled trials (RCTs) remains limited. This study aims 
 Background and Objectives: Various publications have compared outcomes among open (OPDs), laparoscopic (LPDs), and robotic pancreaticoduodenectomies (RPDs); however, the number of randomized controlled trials (RCTs) remains limited. This study aims to conduct a systematic review and analyze the outcomes between these approaches from randomized controlled trials. Materials and Methods: We performed a systematic literature search across PubMed/MedLine, Cochrane Library, ClinicalTrials.gov, and Google Scholar to identify relevant RCTs. The systematic review was conducted using the reporting items for systematic reviews and network meta-analyses guidelines (PRISMA-NMA) and registered in Prospero (CRD420251024475). For statistical analysis R software (version 4.3.2) was used. Results: Eight RCTs involving 1416 patients (706 OPDs, 600 LPDs, 110 RPDs) were included. LPD had a significantly longer operative time than OPD, while RPD showed no significant difference compared to OPD. Blood loss was reduced in both minimally invasive approaches. LPD showed a higher R0 resection rate and lower pancreatic fistula rate, whereas RPD had the lowest mortality. No significant differences were observed in major complications, reoperation, or readmission. LPD shortened hospital stay; RPD showed no difference. Conclusions: Although open pancreaticoduodenectomy remains a well-established standard, both laparoscopic and robotic approaches offer safe alternatives with distinct advantages. LPD is associated with shorter hospital stay and lower pancreatic fistula rates, whereas RPD demonstrates the lowest mortality. The lack of direct randomized comparisons between LPD and RPD highlights the need for further head-to-head trials.

Ablative Five-Fraction CT Versus MR-Guided Stereotactic Body Radiation Therapy for Pancreatic Cancer: In Silico Evaluation of Interfraction Anatomic Changes as a Rationale for Online Adaptive Replanning

2025-06-20
Adeel Kaiser , N. Luther , Kathryn E. Mittauer +7 more | Cancers
Background/Objectives: Non-ablative stereotactic body radiation therapy (SBRT) is commonly employed for locally advanced pancreatic cancer (LAPC) using computed tomography-guided radiotherapy (CTgRT) without online adaptive radiation therapy (oART). The safe delivery 
 Background/Objectives: Non-ablative stereotactic body radiation therapy (SBRT) is commonly employed for locally advanced pancreatic cancer (LAPC) using computed tomography-guided radiotherapy (CTgRT) without online adaptive radiation therapy (oART). The safe delivery of ablative SBRT has been demonstrated using stereotactic magnetic resonance-guided online adaptive radiation therapy (SMART). We performed an in silico comparison of non-adapted CTgRT versus SMART to better understand the potential benefit of oART for ablative pancreatic SBRT. Methods: We retrospectively evaluated original and daily adapted SMART plans that were previously delivered for 20 consecutive LAPC cases (120 total plans across all patients) treated on a 0.35 T MR-linac prescribed to 50 Gy (gross disease) and 33 Gy (elective sites) simultaneously in five fractions. Six comparative CTgRT plans for each patient (one original, five daily treatment) were retrospectively generated with the same prescribed dose and planning parameters as the SMART plans assuming no oART availability. The impact of daily anatomic changes on CTgRT and SMART plans without oART was evaluated across each treatment day MRI scan acquired for SMART. Results: Ninety percent of cases involved the pancreatic head. No statistically significant differences were seen between CTgRT and SMART with respect to target coverage. Nearly all (96%) fractions planned on either CT or MRI platforms exceeded at least one GI organ at risk (OAR) constraint without oART. Significant differences favoring SMART over non-adaptive CTgRT were observed for the duodenum V35 Gy ≀ 0.5 cc (34.2 vs. 41.9 Gy, p = 0.0035) and duodenum V40 Gy ≀ 0.03 cc (37 vs. 52.5 Gy, p = 0.0006) constraints. Stomach V40 Gy trended towards significance favoring SMART (37 vs. 40.3 Gy, p = 0.057) while no significant differences were seen. Conclusions: This is the first study that quantifies the frequency and extent of GI OAR constraint violations that would occur during ablative five-fraction SBRT using SMART vs. CTgRT. GI OAR constraint violations are expected for most fractions without oART whereas all constraints can be achieved with oART. As such, these data suggest that oART should be required for ablative five-fraction pancreatic SBRT.

Distinct microbiome composition and reduced interactions in patients with pancreatic cancer

2025-06-20
Bo‐Mi Kim , Sujin Oh , Soomin Yang +7 more | Frontiers in Microbiology
Introduction The results of microbiome composition in patients with malignancy have been inconsistent across studies and are affected by various factors. This study aimed to identify microbiome composition of saliva, 
 Introduction The results of microbiome composition in patients with malignancy have been inconsistent across studies and are affected by various factors. This study aimed to identify microbiome composition of saliva, feces, and blood in patients with pancreatic cancer. Results Overall, 31 patients with pancreatic cancer and 24 healthy controls were sex- and age-matched. Microbiome analysis of saliva, fecal, and blood samples was conducted using 16S rRNA amplicon sequencing. Baseline characteristics were comparable between patients and controls. Saliva showed insignificant difference in alpha diversity ( p = 0.42), whereas feces and blood exhibited a significant difference in Shannon’s index (feces: 6.19 vs. 6.52, p = 0.013; blood: 8.00 vs. 7.49, p &amp;lt; 0.001) between patients and controls. Beta diversity analysis revealed significant differences between saliva, fecal, and blood samples ( p = 0.014, 0.001, and 0.001, respectively). Distinct microbiome compositions were identified in patients, with higher abundance of Lactobacillus , Enterobacter , and Prevotella in saliva, fecal, and blood samples, respectively. Based on microbial network analysis, patients with pancreatic cancer showed lower clustering coefficient (71% vs. 99%) and higher average path length (1.67 vs. 0.68) than healthy controls, suggesting a more compact network and stronger microbial interactions in healthy controls. Conclusion This study identified a distinctive microbiome in patients with pancreatic cancer, indicating the presence of Lactobacillus , Enterobacter , and Prevotella . A less condensed and robust microbial interaction network was observed in blood samples of patients with pancreatic cancer. These findings provide a basis for research on the connection between the microbiome and pancreatic cancer.

Spatiotemporal Transcriptomic Dissection of Tumor-Associated Macrophage Heterogeneity and Dual-Function Molecular Nodes in Pancreatic Ductal Adenocarcinoma

2025-06-20
Mengfei Li | Theoretical and Natural Science
Many studies have shown that pancreatic cancer is one of the cancers with extremely high mortality. The poor prognosis and lack of early diagnostic methods remain major challenges in the 
 Many studies have shown that pancreatic cancer is one of the cancers with extremely high mortality. The poor prognosis and lack of early diagnostic methods remain major challenges in the treatment of this cancer. In this article, in order to better detect the occurrence of pancreatic cancer, tools such as monocle3, singleR, harmony in R, and scanpy in Python were used to analyze the cells and genes of pancreatic cancer tissues in mice. By analyzing the data, the following results were obtained: T-cells in healthy PBMCs exhibited broader spatial dispersion than in PDAC tissues, suggesting tumor-driven immune surveillance impairment, while PDAC-associated macrophages displayed expanded distribution linked to pro-tumorigenic functions such as COL1A1-mediated ECM remodeling; Pseudotemporal trajectory analysis revealed myeloid progenitor bifurcation into monocytes/macrophages, with PDAC macrophages showing epigenetically silenced cytotoxic pathways such as suppressed GZMA/NKG7 and enhanced ribosomal biogenesis; Tissue-specific markers such as LCN2 in healthy and CTRB1/AMY2A in PDAC) and spatial co-localization of macrophages/tumor cells highlighted NOP53 as a dual-function hubinhibiting PI3K-AKT while activating p53and SPP1 as a paradoxical regulator of metastasis and antitumor immunity; Differential expression and GO enrichment analyses identified ribosomal biogenesis and cytoplasmic translation as PDAC-enriched pathways, contrasting with suppressed stress responses. Our spatial transcriptomic profiling further resolved elevated NOP53, CFB, and SPP1 expression gradients in PDAC tissues, proposing these as diagnostic biomarkers.

Transabdominal ultrasound for the characterization and follow-up of cystic pancreatic lesions

2025-06-20
Julian Seelig , Maria Heni , Max Seitzinger +7 more | Scientific Reports
Abstract Cystic pancreatic lesions (CPL) pose a diagnostic challenge due to their morphological diversity and malignant potential. Given the limited study data, transabdominal ultrasound (TAUS) is currently not established for 
 Abstract Cystic pancreatic lesions (CPL) pose a diagnostic challenge due to their morphological diversity and malignant potential. Given the limited study data, transabdominal ultrasound (TAUS) is currently not established for either primary diagnostics or CPL monitoring. This study compared the diagnostic accuracy of TAUS in the assessment of CPL to that of the reference method, endoscopic ultrasound (EUS), to identify patient subgroups suitable for TAUS monitoring. In a monocentric, retrospective analysis, patients with CPL who underwent EUS and TAUS within six months from 01/2016 to 06/2022 were included. Univariate and multiple logistic regression analyses were used to identify determinants for the detection of CPL via TAUS. Cross-method morphological assessments were analysed, and a patient-specific algorithm for selecting the appropriate monitoring method was developed. Among 105 patients, CPL were detected by both EUS and TAUS in 90 patients (86%). Patients with “TAUS negative” CPL ( n = 15) exhibited greater body mass indices (BMI, p = 0.002) and smaller CPL diameters ( p = 0.043). The final multivariate model (BMI, age, CPL diameter) yielded an 85% accuracy in predicting CPL detectability by TAUS. TAUS could be a cost-effective and patient-friendly imaging method for the surveillance of CPL in selected patients.

International validation of the distal pancreatectomy fistula risk score: evaluation in minimally invasive and open surgery

2025-06-20
Philip C. MĂŒller , Suna Erdem , Christoph Kuemmerli +7 more | Surgical Endoscopy
Abstract Background Postoperative pancreatic fistula (POPF) remains the most severe complication following distal pancreatectomy (DP). The preoperative distal fistula risk score (D-FRS) was introduced to predict the POPF risk. The 
 Abstract Background Postoperative pancreatic fistula (POPF) remains the most severe complication following distal pancreatectomy (DP). The preoperative distal fistula risk score (D-FRS) was introduced to predict the POPF risk. The aim of this study was to externally validate the D-FRS in an international expert center cohort. Methods This international, multicenter, retrospective cohort study included open and minimally invasive DP for benign and malignant lesions performed from 01/2014 until 12/2023 in 12 centres from 6 countries, that each performed more than 50 pancreatectomies annually. The D-FRS was calculated from pancreatic thickness and duct size. Predicted and actual POPF were compared using sensitivity, specificity and area under the curve (AUC). Results A total of 778 patients underwent DP of whom 284 (39%) underwent robotic, 278 (38%) open and 165 (23%) laparoscopic DP. The rate of POPF was 32%. The sensitivity, specificity and AUC of the D-FRS for the overall cohort was 32%, 63% and 48% (95% CI 44–51%), respectively. The AUC for open, laparoscopic and robotic DP was 54% (48–60%), 47% (39–55%) and 45% (39–50%), respectively. For neoadjuvant therapy naïve patients the AUC was 52.3%. On multivariate analysis POPF was associated with body mass index (odds ratio 1.04 (95% CI 1.01–1.07)), protective factors were neoadjuvant therapy (OR 0.54 (0.22–0.94)) and the robotic approach (OR 0.64 (0.42–0.97)). Conclusions The preoperative D-FRS showed insufficient discrimination to identify patients who develop POPF after DP irrespective of the surgical approach. Novel preoperative POPF risk scores are needed, considering the standard minimally invasive approach and the widespread use of neoadjuvant therapy.

Letter to Editor: “Virtual 3D models, augmented reality systems and virtual laparoscopic simulations in complicated pancreatic surgeries state of art, future perspectives, and challenges”

2025-06-20
Jiaqi Yao , Chao Wu , Chi Ma | International Journal of Surgery

Clinical behavior and prognostic factors of pancreatic adenosquamous carcinoma

2025-06-20
Qingxiang Wang , Shijie Wang , Yuyang Jiang +1 more | Journal of Pancreatology
Background: Pancreatic adenosquamous carcinoma (PASC) is a rare subtype of pancreatic malignant neoplasms. The aim of this study was to evaluate the clinical behavior and predictors of prognosis of patients 
 Background: Pancreatic adenosquamous carcinoma (PASC) is a rare subtype of pancreatic malignant neoplasms. The aim of this study was to evaluate the clinical behavior and predictors of prognosis of patients with surgically resected PASC. Methods: Patients with PASC and those with pancreatic ductal adenocarcinoma (PDAC) who underwent potentially curative resection were selected from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2021. Propensity score matching was used to overcome any selection bias. Additional individual patient data identified by literature search were pooled and combined as a new cohort. Factors associated with overall survival were determined by univariate and multivariate analyses. Results: Of the 13544 patients selected from the SEER database, 149 (1.1%) had PASC and 13395 (98.9%) had PDAC. The median survival duration of PASC patients was significantly lower than that of PDAC patients (13.0 versus 21 months, P &lt;0.001), and this survival difference disappeared in multivariate analysis (hazard ratio [HR] =1.178, P =0.105) and after propensity score matching (HR =1.201, P =0.150). Pooled analysis of 118 patients with PASC identified tumor size &gt;4 cm (HR =2.096, P =0.024) and tumor involving multiple segments of the pancreas (HR =3.175, P =0.006) were independent predictors for shorter survival, whereas use of adjuvant therapy (HR =0.484, P =0.019) was related to longer survival. Conclusions: The above findings suggest that the clinical behavior of PASC is similar to that of PDAC after surgical resection, and adjuvant therapy is beneficial to improving the prognosis of PDAC patients.

Chimeric antigen receptor macrophages (CAR-M): New Opportunity in Pancreatic Cancer Treatment

2025-06-20
Yang Cai , Zhijun Zhou , Min Li | Journal of Pancreatology

Prognostic significance of preoperative abdominal fat thickness for pancreatic ductal adenocarcinoma

2025-06-20
Shengqiang Zhang , Longjie Xu , Dekang Gao +2 more | Discover Oncology

Advances in neoadjuvant therapy for pancreatic cancer: Current trends and future directions

2025-06-20
Shang‐Gin Wu , Li Zhu , Feng Xiao-ling +6 more | World Journal of Clinical Oncology
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most challenging malignancies, with poor survival rates due to late-stage diagnosis and limited treatment options. Neoadjuvant therapy (NAT), which involves chemotherapy or 
 Pancreatic ductal adenocarcinoma (PDAC) remains one of the most challenging malignancies, with poor survival rates due to late-stage diagnosis and limited treatment options. Neoadjuvant therapy (NAT), which involves chemotherapy or chemoradiation prior to surgical resection, has emerged as a promising approach to improve resectability and overall survival (OS). The integration of advanced imaging techniques and biomarkers for evaluating the response to NAT is crucial for optimizing therapeutic strategies and surgical outcomes. However, challenges related to the heterogeneity of treatment protocols and the need for predictive biomarkers remain, highlighting the necessity for further clinical trials. The aim is to evaluate the impact of NAT on surgical outcomes and predictive markers in pancreatic cancer. A comprehensive review of the literature was conducted to evaluate the impact of NAT on surgical resectability, survival outcomes, and the role of imaging and biomarkers in assessing therapeutic response. Studies examining the efficacy of NAT in patients with PDAC, the predictive value of serum biomarkers such as carbohydrate antigen 19-9 (CA 19-9), and the utility of advanced imaging modalities such as positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (FDG-PET/CT) were included. NAT has demonstrated significant benefits in downstaging tumors, increasing margin-negative (R0) resection rates, and reducing micrometastatic disease. The use of serum CA 19-9 Levels as a biomarker for response evaluation and imaging modalities such as FDG-PET/CT and magnetic resonance imaging has proven valuable in predicting therapeutic efficacy and guiding surgical planning. Studies have shown that significant reductions in CA 19-9 Levels and favorable metabolic responses on imaging are associated with higher R0 resection rates and longer survival. Furthermore, the integration of multimodal imaging and biomarker assessment has enabled better stratification of patients and more personalized treatment strategies. NAT significantly improves surgical outcomes and survival in patients with resectable and borderline resectable PDAC. Advanced imaging techniques and biomarkers such as CA 19-9 play pivotal roles in evaluating the response to therapy and guiding surgical decision-making. Future research should focus on addressing variability in treatment strategies and developing more reliable predictive biomarkers.

Updates in the diagnosis and management of ductal adenocarcinoma of the pancreas

2025-06-20
T. Pavlidis , I. Galanis | World Journal of Clinical Oncology
Pancreatic ductal adenocarcinoma (PDAC) is characterized by high aggressiveness, poor prognosis, and unsatisfactory survival rates. The incidence of PDAC is increasing annually, and thus, the number of deaths due to 
 Pancreatic ductal adenocarcinoma (PDAC) is characterized by high aggressiveness, poor prognosis, and unsatisfactory survival rates. The incidence of PDAC is increasing annually, and thus, the number of deaths due to PDAC is increasing worldwide. Modern imaging modalities, including multidetector computed tomography, magnetic resonance imaging-cholangiopancreatography, endoscopic retrograde cholangiopancreatography, positron emission tomography-computed tomography, endoscopic ultrasound and tumor markers, have made significant contributions to the diagnosis of pancreatic cancer. However, early diagnosis remains challenging despite progress in liquid biopsy (tumor DNA, tumor parts or cells), miRNAs, genomic analysis, MTA (metastasis-associated) proteins or circulating cancer-derived exosomes. Early diagnosis and radical surgical excision offer a unique chance of long-term survival in patients with an otherwise poor prognosis. However, surgery alone is insufficient, and multimodal treatment is needed. Novel treatment modalities, i.e., immunotherapy, vaccines, targeted gene therapy, extracellular vesicles (particularly exosomes), new chemotherapy, novel radiotherapy and angiogenesis-restricting biological agents, were applied with promising outcomes. It seems that the biological mechanisms underlying the disease determine the effectiveness of any therapeutic effort. Thus, further research at the molecular level must focus on novel treatments to prevent the growth, invasion, and spread of cancer cells.

A classification of laparoscopic central pancreatectomy determined on the basis of anatomical landmarks in 109 patients

2025-06-19
Clément Pastier , Jules Grégory , Marc-Anthony Chouillard +5 more | Surgery

Novel modified blumgart anastomosis reduces clinically relevant pancreatic fistula after pancreaticoduodenectomy: a retrospective study using inverse probability of treatment weighting

2025-06-19
Ye Lin , Zhiyuan Jian , Wai Mun Yue +7 more | Frontiers in Surgery
Background Clinically relevant postoperative pancreatic fistula (CR-POPF) remains a significant complication after pancreaticoduodenectomy (PD). We implemented a novel modified Blumgart pancreaticojejunostomy (m-BPJ) technique with anchoring approach and omental reinforcement, and 
 Background Clinically relevant postoperative pancreatic fistula (CR-POPF) remains a significant complication after pancreaticoduodenectomy (PD). We implemented a novel modified Blumgart pancreaticojejunostomy (m-BPJ) technique with anchoring approach and omental reinforcement, and evaluated its efficacy compared to conventional pancreaticojejunostomy (c-PJ). Methods This retrospective study included patients who underwent PD from January 2020 to December 2024. Patients were divided into m-BPJ ( n = 85) and c-PJ ( n = 130) groups. Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics. The primary endpoint was CR-POPF incidence. Secondary endpoints included operative parameters, postoperative recovery indicators, and complications. Results After IPTW, CR-POPF incidence was significantly lower in the m-BPJ group (6.4% vs. 15.6%, p = 0.031). The m-BPJ group showed shorter PJ anastomosis time (21.1 ± 5.5 vs. 29.0 ± 7.4 min, p &amp;lt; 0.001), operation time (287.5 ± 45.3 vs. 304.2 ± 53.6 min, p = 0.023), and less intraoperative blood loss (325 vs. 375 mL, p = 0.041). Postoperative recovery was accelerated, with faster gastrointestinal function recovery (3.2 ± 1.1 vs. 4.0 ± 1.4 days, p &amp;lt; 0.001), earlier oral intake (4.6 ± 1.3 vs. 5.7 ± 1.8 days, p &amp;lt; 0.001), and reduced hospital stay (12 vs. 14 days, p = 0.009). Multivariate analysis confirmed m-BPJ as an independent protective factor against CR-POPF (OR 0.34, 95% CI 0.13-0.82, p = 0.018), while BMI ≄25 kg/mÂČ (OR 2.23, 95% CI 1.07–4.65, p = 0.033), soft pancreatic texture (OR 3.25, 95% CI 1.47–7.12, p = 0.003), and pancreatic duct diameter &amp;lt;3 mm (OR 2.35, 95% CI 1.12–4.97, p = 0.024) were independent risk factors. Subgroup analysis revealed greatest benefit in high-risk patients. Conclusions Our m-BPJ technique with anchoring approach and omental reinforcement significantly reduces CR-POPF after PD, particularly in high-risk patients. This technique demonstrates improved surgical efficiency and postoperative recovery, providing a valuable option for safer pancreatic reconstruction following PD.

Risk factors for early mortality among patients with gastrointestinal malignancy in the C-CAT database

2025-06-19
Rei Suzuki , Hiroshi Shimizu , Kentaro Sato +7 more | International Journal of Clinical Oncology

Invited Editorial: Clinical Relevance of High-Grade Pancreatic Intraepithelial Neoplasia at the Pancreatic Transection Margin in Patients with Pancreatic Ductal Adenocarcinoma

2025-06-19
Atsushi Oba , Masahiro Yamane , Yu Takahashi | Annals of Surgical Oncology

ASO Author Reflections: From BRPC to LAPC—Rethinking Resectability in Pancreatic Cancer

2025-06-19
Jacob Ghotbi , Ingvild Farnes , Knut JĂžrgen Labori | Annals of Surgical Oncology

Performance of GFR estimation equations in pediatric hematology-oncology patients

2025-06-19
Tyler J. Benning , Asmaa Ferdjallah , Laura Dinnes +3 more | Pediatric Nephrology

The role and therapeutic potential of glucose metabolism in multidrug resistance of cancer

2025-06-19
Qijing Wang , Kai Li , Liang Li +5 more | Frontiers in Cell and Developmental Biology
Cancer represents a serious threat to human health and life. Despite recent advances in the cancer therapy that significantly extend patient survival, many individuals still undergo drug resistance, even to 
 Cancer represents a serious threat to human health and life. Despite recent advances in the cancer therapy that significantly extend patient survival, many individuals still undergo drug resistance, even to multiple chemotherapeutic drugs, known as multidrug resistance (MDR). MDR causes the treatment failure and promotes the risk of tumor recurrence and metastasis, which has been a critical clinical challenge. The molecular mechanisms for cancer cells developing MDR are complex and largely unclarified. ATP-binding cassette (ABC) transporters-mediated enhanced drug efflux and glucose metabolic reprogramming have been recently identified as key factors that limit drug efficacy. In addition to regulating glucose metabolism, several glycolytic enzymes exhibit aberrant cellular localization, including translocation to the nucleus, cell membrane or mitochondria, which imparts their non-classical pro-oncogenic functions to facilitate tumor progression and MDR. In this review, we summarize the roles and molecular insights of glycometabolic enzymes in MDR progression and discuss existing therapeutic strategies of targeting glucose metabolic enzymes for overcoming MDR.