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Revista Espanola de Enfermedades... Sep 2023Due to low incidence rate of pancreatic duct stones,Authoritative consensus has not been reached regarding therapeutic choices in clinical practice. This article...
Due to low incidence rate of pancreatic duct stones,Authoritative consensus has not been reached regarding therapeutic choices in clinical practice. This article reports the treatment of a young woman with chronic pancreatitis complicated with refractory multiple pancreatic duct stones, which provides clinical experience for treatment and provides a new way to study the pathogenesis of chronic pancreatitis complicated with pancreatic duct stones.
Topics: Female; Humans; Pancreatic Ducts; Lithotripsy; Pancreatic Diseases; Pancreatitis, Chronic; Cholangiopancreatography, Endoscopic Retrograde
PubMed: 36562526
DOI: 10.17235/reed.2022.9378/2022 -
Frontiers in Endocrinology 2023Pancreatic signet ring cell carcinoma (PSRCC) is a rare and aggressive cancer that has been reported primarily as case reports. Due to limited large-scale... (Observational Study)
Observational Study
BACKGROUND
Pancreatic signet ring cell carcinoma (PSRCC) is a rare and aggressive cancer that has been reported primarily as case reports. Due to limited large-scale epidemiological and prognostic analyses, the outcomes of PSRCC patients varies greatly in the absence of recognized first-line treatment strategies. This study aimed to compare the clinical features, treatment, and prognosis of PSRCC and pancreatic ductal cell carcinoma (PDAC), the most common subtype of pancreatic cancer, and to establish predictive models for these subtypes.
METHODS
The data on PSRCC and PDAC patients from 1998 to 2018 was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Thereafter, the clinical, demographic, and treatment characteristics of the two groups and the differences and influencing factors of the two groups were evaluated by propensity score matching (PSM), Kaplan-Meier survival curves, Cox risk regression analyses, and least absolute shrinkage and selection operator (LASSO) analysis. Next, prognosis models were constructed and validated by KM and ROC analysis. Finally, a nomogram was constructed, based on the results of these analyses, to predict survival outcomes of PSRCC and PDAC patients.
RESULTS
A total of 84,789 patients (432 PSRCC and 84357 PDAC patients) were included in this study. The results of the study revealed that, compared to the PDAC patients, PSRCC patients were more likely to be male, aged between 58-72 years, have larger tumor masses, and less likely to undergo chemotherapy. Before PSM, the overall survival and cancer-specific survival of the PSRCC group were significantly lower than those PDAC group, but there was no difference in the prognosis of the two groups after PSM. Additionally, lymph node ratio (LNR), log odds of positive lymph node (LODDS), tumor size, age, T-stage, marital status, and summary stage were found to be independent prognostic factors for PSRCC. Lastly, the prediction model and nomogram based on these prognostic factors could accurately predict the survival rate of the patients in SEER datasets and external validation datasets.
CONCLUSION
The prognosis of PSRCC and PDAC patients is similar under the same conditions; however, PSRCC patients may have more difficulty in receiving better treatment, thus resulting in their poor prognosis.
Topics: Humans; Male; Middle Aged; Aged; Female; Prognosis; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Carcinoma, Signet Ring Cell
PubMed: 37534212
DOI: 10.3389/fendo.2023.1205594 -
Journal of Clinical Medicine Jul 2023Pancreatic fistulas are highly feared complications following surgery on or near the pancreas, abdominal trauma, or severe inflammation. These fistulas arise from leaks... (Review)
Review
Pancreatic fistulas are highly feared complications following surgery on or near the pancreas, abdominal trauma, or severe inflammation. These fistulas arise from leaks in the pancreatic ductal system, leading to various complications such as abscesses, delayed gastric emptying, and hemorrhage. Severe cases present with sepsis or organ failure, dramatically increasing mortality and morbidity. Risk factors include smoking, high BMI, male gender, age, and surgery-related factors like prolonged operation time and non-ligation of the main pancreatic duct. Therefore, treatment options and preventive measurements have become a hot topic in recent years. Studies have investigated the use of fibrin sealants, different closure methods, and less invasive surgical techniques. Treatment options consist of conservative measurements and the use of percutaneous drainage, prophylactic transpapillary stenting, and surgery in severe cases. As EUS has become widely available, transmural stenting started to influence the management of pancreatic fluid collections (PFCs). However, studies on its use for the management of pancreatic fistulas are lacking. Medical treatment options like somatostatin analogs and pasireotide have been investigated but yielded mixed results.
PubMed: 37568446
DOI: 10.3390/jcm12155046 -
World Journal of Radiology Jun 2023Preoperative prediction of the postoperative pancreatic fistula risk is critical in the current era of minimally invasive pancreatic surgeries to tailor perioperative... (Review)
Review
Preoperative prediction of the postoperative pancreatic fistula risk is critical in the current era of minimally invasive pancreatic surgeries to tailor perioperative management, thereby minimizing postoperative morbidity. Pancreatic duct diameter can be readily measured by any routine imaging used to diagnose pancreatic disease. However, radiological evaluation of pancreatic texture, an important determinant of pancreatic fistula, has not been widely used to predict the risk of postoperative pancreatic fistula. Qualitative and quantitative assessment of pancreatic fibrosis and fat fraction provides the basis for predicting pancreatic texture. Traditionally computed tomography has been utilized in identifying and characterizing pancreatic lesions and background parenchymal pathologies. With the increasing utilisation of endoscopic ultrasound and magnetic resonance imaging for evaluating pancreatic pathologies, elastography is emerging as a promising tool for predicting pancreatic texture. Also, recent studies have shown that early surgery for chronic pancreatitis is associated with better pain relief and preservation of pancreatic function. Pancreatic texture assessment can allow early diagnosis of chronic pancreatitis, facilitating early intervention. The present review outlines the current evidence in utilizing various imaging modalities for determining the pancreatic texture based on different parameters and image sequences. However, multidisciplinary investigations using strong radiologic-pathologic correlation are needed to standardize and establish the role of these non-invasive diagnostic tools in predicting pancreatic texture.
PubMed: 37424737
DOI: 10.4329/wjr.v15.i6.170 -
Clinical and Translational Medicine Dec 2023Cholangiocarcinoma (CCA) refers to a collection of malignancies that are associated with a dismal prognosis. Currently, surgical resection is the only way to cure...
BACKGROUND
Cholangiocarcinoma (CCA) refers to a collection of malignancies that are associated with a dismal prognosis. Currently, surgical resection is the only way to cure patients with CCA. Available systemic therapy is limited to gemcitabine plus cisplatin; however, this treatment is palliative in nature. Therefore, there is still a need to explore new effective therapeutic targets to intervene against CCA.
METHODS
We analyzed the expression of EZH2 and the prognosis of patients in CCA. The proliferation, migration and invasion of CCA cells after gene knockdown and overexpression were examined and validated by a xenograft model and a primary CCA mouse model with corresponding gene intervention. Targeting DNA methylation, and RNA-sequencing-based transcriptomic analysis in EZH2 and SUZ12 knockout CCA cells was performed. Bisulfite sequencing polymerase chain reaction (PCR), chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) and reverse-ChIP assays were performed for research purposes.
RESULTS
Increased expression of EZH2 in CCA exhibited a significantly poorer prognosis. DNA hypomethylation of the promoter and increased mRNA levels of secreted frizzled-related protein 1 (SFRP1) were observed in CCA cells following the inhibition of polycomb repressor complex 2 (PRC2), which was achieved through a knockout of EZH2, SUZ12 and EED, respectively, or treatment with GSK126 and GSK343. Targeting the SFRP1 promoter DNA hypermethylation with dCas9-DNMT3a decreased the mRNA level of SFRP1. The expression of SFRP1 is regulated by both H3K27me3 and DNA methylation and H3K27me3 plays a crucial role in promoting SFRP1 promotor DNA methylation. GSK343 is a small molecule inhibitor that targets the catalytic activity of EZH2. It effectively inhibits the progression and development of subcutaneous xenografts and primary CCA mouse models.
CONCLUSION
Overall, our data strongly suggested that targeting PRC2 promotes the expression of SFRP1, thereby inhibiting the progression of CCA.
KEY POINTS/HEADLIGHTS
Cholangiocarcinoma (CCA) exhibits elevated expression of EZH2, SUZ12 and EED, resulting in increased levels of H3K27me3. Targeting polycomb repressor complex 2 (PRC2) leads to the removal of H3K27me3 from the secreted frizzled-related protein 1 (SFRP1) promoter and DNA hypomethylation, thereby activating the transcription of SFRP1. Inhibiting PRC2, including the use of EZH2 inhibitors, holds promise as a potential strategy for developing anti-cancer drugs for CCA.
Topics: Animals; Mice; Humans; Histones; Secreted Frizzled-Related Proteins; Enhancer of Zeste Homolog 2 Protein; Epigenesis, Genetic; Cholangiocarcinoma; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; RNA, Messenger; DNA
PubMed: 38050190
DOI: 10.1002/ctm2.1502 -
World Journal of Surgical Oncology Sep 2023Human hydroxysteroid dehydrogenase-like 2 (HSDL2), which regulates cancer progression, is involved in lipid metabolism. However, the role of HSDL2 in cholangiocarcinoma...
BACKGROUND
Human hydroxysteroid dehydrogenase-like 2 (HSDL2), which regulates cancer progression, is involved in lipid metabolism. However, the role of HSDL2 in cholangiocarcinoma (CCA) and the mechanism by which it regulates CCA progression by modulating ferroptosis are unclear.
METHODS
HSDL2 expression levels in CCA cells and tissues were determined by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry. The overall survival and disease-free survival of patients with high vs. low HSDL2 expression were evaluated using Kaplan-Meier curves. The proliferation, migration, and invasion of CCA cells were assessed using Cell Counting Kit-8, colony formation, 5-ethynyl-2'-deoxyuridine DNA synthesis, and transwell assays. The effect of p53 on tumor growth was explored using a xenograft mouse model. The expression of SLC7A11 in patients with CCA was analyzed using immunofluorescence. Ferroptosis levels were measured by flow cytometry, malondialdehyde assay, and glutathione assay. HSDL2-regulated signaling pathways were analyzed by transcriptome sequencing. The correlation between p53 and SLC7A11 was assessed using bioinformatics and luciferase reporter assays.
RESULTS
HSDL2 expression was lower in primary human CCA tissues than in matched adjacent non-tumorous bile duct tissues. HSDL2 downregulation was a significant risk factor for shorter overall survival and disease-free survival in patients with CCA. In addition, HSDL2 knockdown enhanced the proliferation, migration, and invasion of CCA cells. The transcriptome analysis of HSDL2 knockdown cells showed that differentially expressed genes were significantly enriched in the p53 signaling pathway, and HSDL2 downregulation increased SLC7A11 levels. These findings were consistent with the qRT-PCR and western blotting results. Other experiments showed that p53 expression modulated the effect of HSDL2 on CCA proliferation in vivo and in vitro and that p53 bound to the SLC7A11 promoter to inhibit ferroptosis.
CONCLUSIONS
HSDL2 knockdown promotes CCA progression by inhibiting ferroptosis through the p53/SLC7A11 axis. Thus, HSDL2 is a potential prognostic marker and therapeutic target for CCA.
Topics: Humans; Animals; Mice; Tumor Suppressor Protein p53; Ferroptosis; Cholangiocarcinoma; Disease Models, Animal; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Amino Acid Transport System y+; Hydroxysteroid Dehydrogenases
PubMed: 37718459
DOI: 10.1186/s12957-023-03176-6 -
Journal of Nippon Medical School =... Sep 2023Endoscopic retrograde cholangiopancreatography (ERCP) is essential for diagnosing and treating biliopancreatic disease. Because ERCP-related perforation can result in...
BACKGROUND
Endoscopic retrograde cholangiopancreatography (ERCP) is essential for diagnosing and treating biliopancreatic disease. Because ERCP-related perforation can result in death, therapeutic decisions are important. The aim of this study was to determine the cause of ERCP-related perforation and suggest appropriate management.
METHODS
Between January 1999 and August 2022, 7,896 ERCPs were performed in our hospital. We experienced 15 cases (0.18%) of ERCP-related perforation and conducted a retrospective review.
RESULTS
Of the 15 patients, 6 were female and 9 were male, and the mean age was 77.1 years. According to Stapfer's classification, the 15 cases of ERCP-related perforation comprised 3 type I (duodenum), 3 type II (periampullary), 9 type III (distal bile duct or pancreatic duct), and no type IV cases. Fourteen of 15 (92.6%) were diagnosed during ERCP. The main cause of perforation was scope-induced damage, endoscopic sphincterotomy, and instrumentation penetration in type I, II, and III cases, respectively. Four patients with severe abdominal pain and extraluminal fluid collection underwent emergency surgery for repair and drainage. One type III patient with distal bile duct cancer underwent pancreaticoduodenectomy on day 6. Three type III patients with only retroperitoneal gas on computed tomography (CT) performed immediately after ERCP had no symptoms and needed no additional treatment. Seven of the 15 patents were treated by endoscopic nasobiliary drainage (n=5) or CT-guided drainage (n=2). There were no deaths, and all patients were discharged after treatment.
CONCLUSIONS
Early diagnosis and appropriate treatment are important in managing ERCP-related perforation.
Topics: Humans; Male; Female; Aged; Cholangiopancreatography, Endoscopic Retrograde; Retrospective Studies; Treatment Outcome; Early Detection of Cancer; Sphincterotomy, Endoscopic; Intestinal Perforation
PubMed: 37271549
DOI: 10.1272/jnms.JNMS.2023_90-305 -
Revista Espanola de Enfermedades... Jan 2024We present the case of an 82-year-old woman with a history of well-differentiated adenocarcinoma of the cecum, stage pT3N1M0, treated ten years before with right...
We present the case of an 82-year-old woman with a history of well-differentiated adenocarcinoma of the cecum, stage pT3N1M0, treated ten years before with right hemicolectomy and adjuvant chemotherapy (Capecitabine and Bevacizumab). She developed painless obstructive jaundice of sudden onset. Computed tomography (CT) showed an ampullary nodule with secondary dilatation of the biliary and the pancreatic ducts. Subsequent duodenoscopy and endoscopic ultrasound identified the presence of multiple 3-10 mm tumor-like nodules from the first to the second duodenal knee, the largest one infiltrating the papillary area and preventing its cannulation. Biopsy revealed a moderately differentiated adenocarcinoma with cribriform, nidiform and acinar architectural patterns and positive immunohistochemistry for CK20 and CDX2, compatible with colon origin. The patient was treated with five cycles of chemotherapy (FOLFOX) with the disappearance of the duodenal nodules, although during follow-up she developed disease progression with a left adnexal metastasis with identical histological and immunohistochemical pattern.
PubMed: 38258804
DOI: 10.17235/reed.2024.10089/2023 -
NPJ Regenerative Medicine Aug 2023A network of co-hepato/pancreatic stem/progenitors exists in pigs and humans in Brunner's Glands in the submucosa of the duodenum, in peribiliary glands (PBGs) of...
A network of co-hepato/pancreatic stem/progenitors exists in pigs and humans in Brunner's Glands in the submucosa of the duodenum, in peribiliary glands (PBGs) of intrahepatic and extrahepatic biliary trees, and in pancreatic duct glands (PDGs) of intrapancreatic biliary trees, collectively supporting hepatic and pancreatic regeneration postnatally. The network is found in humans postnatally throughout life and, so far, has been demonstrated in pigs postnatally at least through to young adulthood. These stem/progenitors in vivo in pigs are in highest numbers in Brunner's Glands and in PDGs nearest the duodenum, and in humans are in Brunner's Glands and in PBGs in the hepato/pancreatic common duct, a duct missing postnatally in pigs. Elsewhere in PDGs in pigs and in all PDGs in humans are only committed unipotent or bipotent progenitors. Stem/progenitors have genetic signatures in liver/pancreas-related RNA-seq data based on correlation, hierarchical clustering, differential gene expression and principal component analyses (PCA). Gene expression includes representative traits of pluripotency genes (SOX2, OCT4), endodermal transcription factors (e.g. SOX9, SOX17, PDX1), other stem cell traits (e.g. NCAM, CD44, sodium iodide symporter or NIS), and proliferation biomarkers (Ki67). Hepato/pancreatic multipotentiality was demonstrated by the stem/progenitors' responses under distinct ex vivo conditions or in vivo when patch grafted as organoids onto the liver versus the pancreas. Therefore, pigs are logical hosts for translational/preclinical studies for cell therapies with these stem/progenitors for hepatic and pancreatic dysfunctions.
PubMed: 37528116
DOI: 10.1038/s41536-023-00303-5