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Magnetic Resonance in Medical Sciences... Jun 2024To compare the utility of thin-slice fat-suppressed single-shot T2-weighted imaging (T2WI) with deep learning image reconstruction (DLIR) and conventional fast spin-echo...
PURPOSE
To compare the utility of thin-slice fat-suppressed single-shot T2-weighted imaging (T2WI) with deep learning image reconstruction (DLIR) and conventional fast spin-echo T2WI with DLIR for evaluating pancreatic protocol.
METHODS
This retrospective study included 42 patients (mean age, 70.2 years) with pancreatic cancer who underwent gadoxetic acid-enhanced MRI. Three fat-suppressed T2WI, including conventional fast-spin echo with 6 mm thickness (FSE 6 mm), single-shot fast-spin echo with 6 mm and 3 mm thickness (SSFSE 6 mm and SSFSE 3 mm), were acquired for each patient. For quantitative analysis, the SNRs of the upper abdominal organs were calculated between images with and without DLIR. The pancreas-to-lesion contrast on DLIR images was also calculated. For qualitative analysis, two abdominal radiologists independently scored the image quality on a 5-point scale in the FSE 6 mm, SSFSE 6 mm, and SSFSE 3 mm with DLIR.
RESULTS
The SNRs significantly improved among the three T2-weighted images with DLIR compared to those without DLIR in all patients (P < 0.001). The pancreas-to-lesion contrast of SSFSE 3 mm was higher than those of the FSE 6 mm (P < 0.001) and tended to be higher than SSFSE 6 mm (P = 0.07). SSFSE 3 mm had the highest image qualities regarding pancreas edge sharpness, pancreatic duct clarity, and overall image quality, followed by SSFSE 6 mm and FSE 6 mm (P < 0.0001).
CONCLUSION
SSFSE 3 mm with DLIR demonstrated significant improvements in SNRs of the pancreas, pancreas-to-lesion contrast, and image quality more efficiently than did SSFSE 6 mm and FSE 6 mm. Thin-slice fat-suppressed single-shot T2WI with DLIR can be easily implemented for pancreatic MR protocol.
PubMed: 38910138
DOI: 10.2463/mrms.mp.2024-0017 -
Cell Death & Disease Jun 2024TBX3 behaves as a tumor suppressor or oncoprotein across cancer. However, TBX3 function remains undetermined in intrahepatic cholangiocarcinoma (iCCA), a deadly primary...
TBX3 behaves as a tumor suppressor or oncoprotein across cancer. However, TBX3 function remains undetermined in intrahepatic cholangiocarcinoma (iCCA), a deadly primary liver malignancy with few systemic treatment options. This study sought to investigate the impact of TBX3 on iCCA. We found that overexpression of TBX3 strongly inhibited human iCCA cell growth. In the Akt/FBXW7ΔF mouse iCCA model, overexpression of Tbx3 reduced cholangiocarcinogenesis in vivo, while inducible genetic knockout of Tbx3 accelerated iCCA growth. RNA-seq identified MAD2L1 as a downregulated gene in TBX3-overexpressing cells, and ChIP confirmed that TBX3 binds to the MAD2L1 promoter. CRISPR-mediated knockdown of Mad2l1 significantly reduced the growth of two iCCA models in vivo. Finally, we found that TBX3 expression is upregulated in ~20% of human iCCA samples, and its high expression is associated with less proliferation and better survival. MAD2L1 expression is upregulated in most human iCCA samples and negatively correlated with TBX3 expression. Altogether, our findings suggest that overexpression of TBX3 suppresses CCA progression via repressing MAD2L1 expression.
Topics: Cholangiocarcinoma; T-Box Domain Proteins; Humans; Animals; Mice; Bile Duct Neoplasms; Carcinogenesis; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Cell Proliferation
PubMed: 38909034
DOI: 10.1038/s41419-024-06839-8 -
Gastroenterology Jun 2024Pancreatic ducts form an intricate network of tubules that secrete bicarbonate and drive acinar secretions into the duodenum. This network is formed by centroacinar...
BACKGROUND AND AIMS
Pancreatic ducts form an intricate network of tubules that secrete bicarbonate and drive acinar secretions into the duodenum. This network is formed by centroacinar cells, terminal, intercalated, intracalated ducts, and the main pancreatic duct. Ductal heterogeneity at the single-cell level has been poorly characterized; therefore, our understanding of the role of ductal cells in pancreas regeneration and exocrine pathogenesis has been hampered by the limited knowledge and unexplained diversity within the ductal network.
METHODS
We used scRNA-seq to comprehensively characterize mouse ductal heterogeneity at single-cell resolution of the entire ductal epithelium from centroacinar cells to the main duct. Moreover, we used organoid cultures, injury models and pancreatic tumor samples to interrogate the role of novel ductal populations in pancreas regeneration and exocrine pathogenesis.
RESULTS
We have identified the coexistence of 15 ductal populations within the healthy pancreas and characterized their organoid formation capacity and endocrine differentiation potential. Cluster isolation and subsequent culturing let us identify ductal cell populations with high organoid formation capacity and endocrine and exocrine differentiation potential in vitro, including Wnt-responsive-population, ciliated-population and FLRT3 cells. Moreover, we have characterized the location of these novel ductal populations in healthy pancreas, chronic pancreatitis, and tumor samples. The expression of WNT-responsive, IFN-responsive and EMT-population markers increases in chronic pancreatitis and tumor samples.
CONCLUSIONS
In light of our discovery of previously unidentified ductal populations, we unmask potential roles of specific ductal populations in pancreas regeneration and exocrine pathogenesis. Thus, novel lineage tracing models are needed to investigate ductal specific populations in vivo.
PubMed: 38908487
DOI: 10.1053/j.gastro.2024.06.008 -
Gastroenterologia Y Hepatologia Jun 2024Endoscopic ultrasound-guided pancreatic duct intervention (EUS-PDI) is one of the most technically challenging procedures. There remains a knowledge gap due to its...
BACKGROUND AND AIMS
Endoscopic ultrasound-guided pancreatic duct intervention (EUS-PDI) is one of the most technically challenging procedures. There remains a knowledge gap due to its rarity. The aim is to report the accumulated EUS-PDI experience in a tertiary center.
METHODS
Single-tertiary center, retrospective cohort study of prospectively collected data during the study period, from Jan 2013-June 2021.
RESULTS
In total, 14 patients (85% male; mean age, 61years, range:37-81) and 25 EUS-PDI procedures for unsuccessful endoscopic retrograde pancreatography (ERP) were included. Principal etiology was chronic pancreatitis with pancreatic duct obstruction (78%). EUS-guided assisted (colorant and/or guidewire, rendezvous) ERP was performed in 14/25(56%); and transmural drainage in 11procedures, including pancreaticogastrosmy in 9/25(36%) and pancreaticoduodenostomy in 2/25(8%). Overall technical and clinical success was 78.5%(11/14). Three (21%) patients required a second procedure with success in all cases. Two failed cases required surgery. Three (21%) adverse events(AEs) were noted (fever, n=1; perforation n=1; pancreatitis n=1). Patients underwent a median of 58months (range 24-108) follow-up procedures for re-stenting. Spontaneous stent migration was detected in 50% of cases.
CONCLUSIONS
EUS-PDI is an effective salvage therapy for unsuccessful ERP, although 21% of patients may still experience AEs. In case of EUS-guided rendezvous failure, it can cross over to a transmural drainage.
PubMed: 38906323
DOI: 10.1016/j.gastrohep.2024.502221 -
Annals of Surgery Jun 2024Patients with pancreatic cancer and obstructive jaundice routinely undergo endoscopic stent placement (ES). It is well known that ES causes bacterial contamination and...
BACKGROUND
Patients with pancreatic cancer and obstructive jaundice routinely undergo endoscopic stent placement (ES). It is well known that ES causes bacterial contamination and infectious complications after pancreatic resection.
OBJECTIVE
To compare short-term outcomes and survival in patients undergoing pancreatic head resection after preoperative ES vs preoperative surgical drainage (SD) via T-tube insertion.
METHODS
Patients with obstructive jaundice who underwent SD or ES from 2016 to 2022 were identified from a prospective database. Outcome analyses included microbiological bile contamination, overall morbidity and assessment of the overall complication burden using the Comprehensive Complication Index (CCI). Overall survival was investigated by Kaplan‒Meier analysis.
RESULTS
A total of 55 patients with SD were identified and matched with 110 ES patients. After the primary intervention, ES patients experienced more complications (ES: 17.3% vs. SD: 3.6%; P=0.013). The overall complication burden after pancreatic resection was higher in ES patients than in SD patients (CCI: 27.2 vs. 19.9; P=0.022). Additionally, bacterial contamination of the bile was more frequent in ES patients compared to SD individuals (94.3% vs. 7.1%; P<0.001) with similar bacteria in 83.3% of postoperative abdominal infections in ES patients. While overall survival did not differ between the two groups, patients with postinterventional complications after ES had an impaired survival compared to those without complications (11.3 mo vs. 20.4 mo; P=0.03).
CONCLUSION
SD for obstructive jaundice in resectable pancreatic cancer is associated with a lower overall complication burden. Additionally, patients with complications after ES experience worse overall survival. These findings indicate to rethink our standards of treatment of obstructive jaundice in patients with pancreatic cancer.
PubMed: 38904102
DOI: 10.1097/SLA.0000000000006407 -
Clinical Journal of Gastroenterology Jun 2024Acute obstructive suppurative pancreatic ductitis (AOSPD) is an acute suppuration of the pancreatic duct. Endoscopic retrograde cholangiopancreatography (ERCP) drainage...
Acute obstructive suppurative pancreatic ductitis (AOSPD) is an acute suppuration of the pancreatic duct. Endoscopic retrograde cholangiopancreatography (ERCP) drainage and intravenous antibiotics treatment is the mainstay of therapy. Herein we describe an extremely rare case of AOSPD leading to pyogenic spondylitis. A 61-year-old male with a past medical history of chronic pancreatitis and diabetes mellitus presented to our hospital with abdominal and dorsal pain, fever, and shock status. Laboratory data showed severe inflammation, disseminated intravascular coagulation, and normal pancreatic enzymes. Computed tomography showed dilated main pancreatic duct and surrounding pancreatic abscesses. Spinal abnormalities were not detected at this point. He was initially diagnosed as infected pancreatic pseudocyst, but did not respond well to conservative intravenous antibiotic treatment. ERCP performed one week later revealed purulent pancreatic juice and the diagnosis was changed to AOSPD. Upon ERCP, we experienced technical difficulty in passing obstructing calculi. However, successful pancreatic drainage was achieved using new dilation and penetration devices. The patient responded quickly to drainage, but later developed pyogenic spondylitis. Our case highlights the difficulty of diagnosing AOSPD, the usefulness of new devices in urgent endoscopic drainage, and underscores the possibility of progression of pyogenic spondylitis even after adequate treatment.
PubMed: 38902593
DOI: 10.1007/s12328-024-02004-y -
Abdominal Radiology (New York) Jun 2024Pancreatic leaks occur when a disruption in the pancreatic ductal system results in the leakage of pancreatic enzymes such as amylase, lipase, and proteases into the... (Review)
Review
Pancreatic leaks occur when a disruption in the pancreatic ductal system results in the leakage of pancreatic enzymes such as amylase, lipase, and proteases into the abdominal cavity. While often associated with pancreatic surgical procedures, trauma and necrotizing pancreatitis are also common culprits. Cross-sectional imaging, particularly computed tomography, plays a crucial role in assessing postoperative conditions and identifying both early and late complications, including pancreatic leaks. The presence of fluid accumulation or hemorrhage near an anastomotic site strongly indicates a pancreatic fistula, particularly if the fluid is connected to the pancreatic duct or anastomotic suture line. Pancreatic fistulas are a type of pancreatic leak that carries a high morbidity rate. Early diagnosis and assessment of pancreatic leaks require vigilance and an understanding of its imaging hallmarks to facilitate prompt treatment and improve patient outcomes. Radiologists must maintain vigilance and understand the imaging patterns of pancreatic leaks to enhance diagnostic accuracy. Ongoing improvements in surgical techniques and diagnostic approaches are promising for minimizing the prevalence and adverse effects of pancreatic fistulas. In this pictorial review, our aim is to facilitate for radiologists the comprehension of pancreatic leaks and their essential imaging patterns.
PubMed: 38900317
DOI: 10.1007/s00261-024-04401-w -
Journal of Gastroenterology Jun 2024Pancreatic ductal occlusion can accompany pancreatic head cancer, leading to pancreatic exocrine insufficiency (PEI) and adverse effects on nutritional status and...
BACKGROUND
Pancreatic ductal occlusion can accompany pancreatic head cancer, leading to pancreatic exocrine insufficiency (PEI) and adverse effects on nutritional status and postoperative outcomes. We investigated its impact on nutritional status, body composition, and postoperative outcomes in patients with pancreatic head cancer undergoing neoadjuvant therapy (NAT).
METHODS
We analyzed 136 patients with pancreatic head cancer who underwent NAT prior to intended pancreaticoduodenectomy (PD) between 2015 and 2022. Nutritional and anthropometric indices (body mass index [BMI], albumin, prognostic nutritional index [PNI], Glasgow prognostic score, psoas muscle index, subcutaneous adipose tissue index [SATI], and visceral adipose tissue index) and postoperative outcomes were compared between the occlusion (n = 78) and non-occlusion (n = 58) groups, in which 61 and 44 patients, respectively, ultimately underwent PD.
RESULTS
The occlusion group showed significantly lower post-NAT BMI, PNI, and SATI (p = 0.011, 0.005, and 0.015, respectively) in the PD cohort. The occlusion group showed significantly larger main pancreatic duct, smaller pancreatic parenchyma, and greater duct-parenchymal ratio (p < 0.001), and these morphological parameters significantly correlating with post-NAT nutritional and anthropometric indices. Postoperative 3-year survival and recurrence-free survival (RFS) rates were significantly poorer (p = 0.004 and 0.013) with pancreatic ductal occlusion, also identified as an independent postoperative risk factor for overall survival (hazard ratio [HR]: 2.31, 95% confidence interval [CI] 1.08-4.94, p = 0.030) and RFS (HR: 2.03, 95% CI 1.10-3.72, p = 0.023), in multivariate analysis.
CONCLUSIONS
Pancreatic ductal occlusion may be linked to poorer postoperative outcomes due to PEI-related malnutrition.
PubMed: 38900299
DOI: 10.1007/s00535-024-02125-8 -
World Journal of Gastroenterology Jun 2024Pancreatic cancer (PC) is associated with some of the worst prognoses of all major cancers. Thymoquinone (TQ) has a long history in traditional medical practice and is...
BACKGROUND
Pancreatic cancer (PC) is associated with some of the worst prognoses of all major cancers. Thymoquinone (TQ) has a long history in traditional medical practice and is known for its anti-cancer, anti-inflammatory, anti-fibrosis and antioxidant pharmacological activities. Recent studies on hypoxia-inducible factor-1α (HIF-1α) and PC have shown that HIF-1α affects the occurrence and development of PC in many aspects. In addition, TQ could inhibit the development of renal cancer by decreasing the expression of HIF-1α. Therefore, we speculate whether TQ affects HIF-1α expression in PC cells and explore the mechanism.
AIM
To elucidate the effect of TQ in PC cells and the regulatory mechanism of HIF-1α expression.
METHODS
Cell counting kit-8 assay, Transwell assay and flow cytometry were performed to detect the effects of TQ on the proliferative activity, migration and invasion ability and apoptosis of PANC-1 cells and normal pancreatic duct epithelial (hTERT-HPNE) cells. Quantitative real-time polymerase chain reaction and western blot assay were performed to detect the expression of HIF-1α mRNA and protein in PC cells. The effects of TQ on the HIF-1α protein initial expression pathway and ubiquitination degradation in PANC-1 cells were examined by western blot assay and co-immunoprecipitation.
RESULTS
TQ significantly inhibited proliferative activity, migration, and invasion ability and promoted apoptosis of PANC-1 cells; however, no significant effects on hTERT-HPNE cells were observed. TQ significantly reduced the mRNA and protein expression levels of HIF-1α in PANC-1, AsPC-1, and BxPC-3 cells. TQ significantly inhibited the expression of the HIF-1α initial expression pathway (PI3K/AKT/mTOR) related proteins, and promoted the ubiquitination degradation of the HIF-1α protein in PANC-1 cells. TQ had no effect on the hydroxylation and von Hippel Lindau protein mediated ubiquitination degradation of the HIF-1α protein but affected the stability of the HIF-1α protein by inhibiting the interaction between HIF-1α and HSP90, thus promoting its ubiquitination degradation.
CONCLUSION
The regulatory mechanism of TQ on HIF-1α protein expression in PC cells was mainly to promote the ubiquitination degradation of the HIF-1α protein by inhibiting the interaction between HIF-1α and HSP90; Secondly, TQ reduced the initial expression of HIF-1α protein by inhibiting the PI3K/AKT/mTOR pathway.
Topics: Benzoquinones; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; HSP90 Heat-Shock Proteins; Pancreatic Neoplasms; Proto-Oncogene Proteins c-akt; TOR Serine-Threonine Kinases; Cell Line, Tumor; Signal Transduction; Cell Proliferation; Apoptosis; Cell Movement; Phosphatidylinositol 3-Kinases; Gene Expression Regulation, Neoplastic; Neoplasm Invasiveness
PubMed: 38899332
DOI: 10.3748/wjg.v30.i21.2793 -
Cureus May 2024Pancreatic adenocarcinoma refers to cancer of the pancreatic duct cells. It is normally diagnosed when it is at an advanced stage, making the prognosis poor. Systemic... (Review)
Review
Pancreatic adenocarcinoma refers to cancer of the pancreatic duct cells. It is normally diagnosed when it is at an advanced stage, making the prognosis poor. Systemic chemotherapy is the primary treatment approach for locally advanced or metastatic pancreatic cancer and has been shown to improve survival by eight to 16 weeks. However, it does not directly penetrate malignant tissue and has many side effects, such as hair loss, bone marrow suppression, and many gastrointestinal issues. A newer treatment modality, regional intra-arterial chemotherapy (IAC), focuses on targeting malignant tissue directly to improve survival and decrease systemic side effects. When IAC is used with gemcitabine (GEM) or FLEC (5-fluorouracil, leucovorin, epirubicin, and carboplatin), the response rate for advanced pancreatic cancer is significantly improved. This literature review introduces the use of hepatic intra-arterial chemotherapy in patients with metastatic pancreatic adenocarcinoma.
PubMed: 38899244
DOI: 10.7759/cureus.60696