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2.
BMC Pediatr ; 24(1): 243, 2024 Apr 05.
Article En | MEDLINE | ID: mdl-38580968

Cholangiocarcinoma in patients with Choledochal cysts is rare in childhood; however, it seriously affects the prognosis of the disease. The key to addressing this situation lies in completely removing the extrahepatic cyst. We herein present a case report of a 3-year-old boy with cholangiocarcinoma associated with a choledochal cyst (CDC). Preoperative 3D simulation, based on CT data, played an important role in the treatment of this patient.


Bile Duct Neoplasms , Cholangiocarcinoma , Choledochal Cyst , Male , Humans , Child, Preschool , Choledochal Cyst/complications , Choledochal Cyst/diagnostic imaging , Choledochal Cyst/surgery , Cholangiocarcinoma/complications , Cholangiocarcinoma/diagnostic imaging , Cholangiocarcinoma/pathology , Bile Ducts, Intrahepatic/diagnostic imaging , Bile Ducts, Intrahepatic/pathology , Bile Duct Neoplasms/complications , Bile Duct Neoplasms/diagnostic imaging , Bile Duct Neoplasms/pathology
3.
Am J Surg Pathol ; 48(6): 751-760, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38584480

Intrahepatic cholangiocarcinoma (iCCA) has been newly subclassified into two different subtypes: large-duct (LD) type and small-duct (SD) type. However, many cases are difficult to subclassify, and there is no consensus regarding subclassification criteria. LD type expresses the highly sensitive diagnostic marker S100 calcium-binding protein P (S100P), while SD type lacks sensitive markers. We identified osteopontin (OPN) as a highly sensitive marker for SD type. This study aimed to develop new subclassification criteria for LD-type and SD-type iCCA. We retrospectively investigated 74 patients with iCCA and subclassified them based on whole-section immunostaining of S100P and OPN. Of the 74 cases, 41 were subclassified as LD type, 32 as SD type, and one was indeterminate. Notably, all S100P-negative cases had OPN positivity. Seventy-three of the 74 cases (98.6%) were clearly and easily subclassified as LD or SD type using only these 2 markers. We also determined the value of immunohistochemistry in cases that were difficult to diagnose based on hematoxylin-eosin and Alcian blue-periodic acid-Schiff staining. Furthermore, we analyzed the clinicopathological characteristics and prognoses of these 2 subtypes. LD type was a poor prognostic factor on univariate analysis; it had significantly worse overall survival ( P = 0.007) and recurrence-free survival ( P < 0.001) than the SD type. In conclusion, we propose new subclassification criteria for iCCA based on immunostaining of S100P and OPN. These criteria may help pathologists to diagnose subtypes of iCCA, supporting future clinical trials and the development of medications for these 2 subtypes as distinct cancers.


Bile Duct Neoplasms , Biomarkers, Tumor , Calcium-Binding Proteins , Cholangiocarcinoma , Immunohistochemistry , Osteopontin , Humans , Cholangiocarcinoma/pathology , Cholangiocarcinoma/classification , Cholangiocarcinoma/mortality , Cholangiocarcinoma/chemistry , Cholangiocarcinoma/diagnosis , Osteopontin/analysis , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/classification , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/chemistry , Bile Duct Neoplasms/diagnosis , Male , Female , Middle Aged , Biomarkers, Tumor/analysis , Aged , Retrospective Studies , Calcium-Binding Proteins/analysis , Adult , Aged, 80 and over , Neoplasm Proteins/analysis , Predictive Value of Tests , Bile Ducts, Intrahepatic/pathology , Bile Ducts, Intrahepatic/chemistry
4.
Gan To Kagaku Ryoho ; 51(4): 470-472, 2024 Apr.
Article Ja | MEDLINE | ID: mdl-38644325

A 91-year-old man had a history of cholecystectomy and choledochostomy for cholecystolithiasis and choledocholithiasis. Eleven years earlier, intrahepatic stones were found in the posterior bile duct, and he did not wish to undergo treatment. Over time, worsening of the intrahepatic stones and dilation of the intrahepatic bile duct were observed. At 91 years old, enhanced abdominal CT revealed wall thickening of the hilar bile duct, and MRCP showed stenosis of the hilar bile duct. Endoscopic retrograde cholangiography showed no contrast in the right intrahepatic bile duct and marked dilation of the left intrahepatic bile duct. Brush cytology confirmed adenocarcinoma, leading to a diagnosis of hilar cholangiocarcinoma. He underwent open right and caudal lobectomy with biliary reconstruction. Histopathological examination revealed a hilar cholangiocarcinoma, T3N1M0, Stage Ⅲc, mainly located at the confluence of the right and left hepatic ducts. This case suggests a potential association between hepatolithiasis and hilar cholangiocarcinoma, emphasizing the importance of regular imaging examinations for timely surgical resection. Early intervention, including liver resection, is recommended for the management of hepatolithiasis.


Bile Duct Neoplasms , Cholangiocarcinoma , Humans , Male , Bile Duct Neoplasms/surgery , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/diagnostic imaging , Aged, 80 and over , Cholangiocarcinoma/surgery , Time Factors , Lithiasis/surgery , Bile Ducts, Intrahepatic/surgery , Bile Ducts, Intrahepatic/pathology , Hepatectomy , Follow-Up Studies , Liver Diseases/surgery , Klatskin Tumor/surgery , Klatskin Tumor/pathology
5.
World J Surg Oncol ; 22(1): 105, 2024 Apr 20.
Article En | MEDLINE | ID: mdl-38643155

BACKGROUND: Biliary intraepithelial neoplasia (BilIN), a noninvasive precursor of cholangiocarcinoma, can manifest malignant transformation. Since cholangiocarcinoma (CCA) may progress due to chronic inflammation in the bile ducts and gallbladder, choledochal cysts are considered a precursor to CCA. However, BilIN has rarely been reported in children, to date. METHODS: We reviewed medical records of patients (< 18 years of age, n = 329) who underwent choledochal cyst excision at Asan Medical Center from 2008 to 2022. BilIN was diagnosed in 15 patients. Subsequent analyses were performed of the demographics, surgical procedures, clinical course, and outcomes in these patients. Subgroup analysis and multivariate logistic regression test were performed to identify factors influencing BilIN occurrence. RESULTS: The mean age of the patients included in our study was 40.1 ± 47.6 months. In 15 patients, BilIN of various grades was diagnosed. Todani type I was prevalent in 80% of the patients. The median age at surgery was 17 months. During a mean follow-up of 63.3 ± 94.0 months, no adverse events such as stone formation in the remnant intrapancreatic common bile duct and intrahepatic duct or cholangiocarcinoma were observed, indicating a favorable outcome until now. CONCLUSIONS: The potential progression of choledochal cysts to BilIN in children was demonstrated. These results could underscore the importance of early and comprehensive excision of choledochal cysts, including resection margins for associated lesions and more thorough postoperative surveillance in patients with or at risk of BilIN.


Bile Duct Neoplasms , Carcinoma in Situ , Cholangiocarcinoma , Choledochal Cyst , Humans , Child , Child, Preschool , Infant , Choledochal Cyst/diagnosis , Choledochal Cyst/surgery , Choledochal Cyst/epidemiology , Bile Ducts, Intrahepatic/pathology , Bile Duct Neoplasms/diagnosis , Bile Duct Neoplasms/surgery , Bile Duct Neoplasms/epidemiology , Cholangiocarcinoma/diagnosis , Cholangiocarcinoma/surgery , Cholangiocarcinoma/epidemiology , Carcinoma in Situ/diagnosis , Carcinoma in Situ/surgery , Bile Pigments
6.
Pharm Biol ; 62(1): 314-325, 2024 Dec.
Article En | MEDLINE | ID: mdl-38571483

CONTEXT: Cholangiocarcinoma with highly heterogeneous, aggressive, and multidrug resistance has a poor prognosis. Although babaodan (BBD) combined with cisplatin improved non-small cell lung cancer efficacy, its impact on overcoming resistance in cholangiocarcinoma remains unexplored. OBJECTIVE: This study explored the role and mechanism of BBD on cisplatin resistance in cholangiocarcinoma cells (CCAs). MATERIALS AND METHODS: Cisplatin-resistant CCAs were exposed to varying concentrations of cisplatin (25-400 µg/mL) or BBD (0.25-1.00 mg/mL) for 48 h. IC50 values, inhibition ratios, apoptosis levels, DNA damage, glutathione (GSH) levels, oxidized forms of GSH, total GSH content, and glutaminase relative activity were evaluated using the cell counting kit 8, flow cytometry, comet assay, and relevant assay kits. RESULTS: BBD-reduced the cisplatin IC50 in CCAs from 118.8 to 61.83 µg/mL, leading to increased inhibition rate, apoptosis, and DNA damage, and decreased expression of B-cell lymphoma-2, p-Yes-associated protein 1/Yes-associated protein 1, solute carrier family 1 member 5, activating transcription factor 4, and ERCC excision repair 1 in a dose-dependent manner with maximum reductions of 78.97%, 51.98%, 54.03%, 56.59%, and 63.22%, respectively; bcl2-associated X and gamma histone levels were increased by 0.43-115.77% and 22.15-53.39%. The impact of YAP1 knockdown on cisplatin-resistant CCAs resembled BBD. GSH, oxidized GSH species, total GSH content, and glutaminase activity in cisplatin-resistant CCAs with BBD treatment also decreased, while YAP1 overexpression countered BBD's effects. DISCUSSION AND CONCLUSION: This study provides a scientific basis for BBD clinical application and provides a new direction for BBD biological mechanism research.


Antineoplastic Agents , Bile Duct Neoplasms , Carcinoma, Non-Small-Cell Lung , Cholangiocarcinoma , Lung Neoplasms , Humans , Cisplatin/pharmacology , YAP-Signaling Proteins , Carcinoma, Non-Small-Cell Lung/drug therapy , Glutaminase/metabolism , Glutaminase/pharmacology , Glutaminase/therapeutic use , Lung Neoplasms/drug therapy , Transcription Factors/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Cholangiocarcinoma/drug therapy , Cholangiocarcinoma/genetics , Cholangiocarcinoma/pathology , Bile Duct Neoplasms/drug therapy , Bile Ducts, Intrahepatic/metabolism , Bile Ducts, Intrahepatic/pathology , Drug Resistance, Neoplasm , Apoptosis , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cell Line, Tumor
7.
World J Gastroenterol ; 30(10): 1461-1465, 2024 Mar 14.
Article En | MEDLINE | ID: mdl-38596486

Pancreatobiliary intraductal papillary neoplasms (IPNs) represent precursors of pancreatic cancer or bile duct cholangiocarcinoma that can be detected and treated. Despite advances in diagnostic methods, identifying these premalignant lesions is still challenging for treatment providers. Modern imaging, biomarkers and molecular tests for genomic alterations can be used for diagnosis and follow-up. Surgical intervention in combination with new chemotherapeutic agents is considered the optimal treatment for malignant cases. The balance between the risk of malignancy and any risk of resection guides management policy; therefore, treatment should be individualized based on a meticulous preoperative assessment of high-risk stigmata. IPN of the bile duct is more aggressive; thus, early diagnosis and surgery are crucial. The conservative management of low-risk pancreatic branch-duct lesions is safe and effective.


Bile Duct Neoplasms , Cholangiocarcinoma , Pancreatic Neoplasms , Humans , Bile Duct Neoplasms/surgery , Bile Duct Neoplasms/genetics , Cholangiocarcinoma/surgery , Cholangiocarcinoma/genetics , Bile Ducts, Intrahepatic/diagnostic imaging , Bile Ducts, Intrahepatic/pathology , Bile Ducts/pathology , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/pathology , Pancreatic Ducts/diagnostic imaging , Pancreatic Ducts/pathology
8.
World J Gastroenterol ; 30(9): 1018-1042, 2024 Mar 07.
Article En | MEDLINE | ID: mdl-38577184

A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26, 2023, at the Pakistan Kidney and Liver Institute & Research Centre (PKLI & RC) after initial consultations with the experts. The Pakistan Society for the Study of Liver Diseases (PSSLD) and PKLI & RC jointly organised this meeting. This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma (hCCA). The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients. This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation. The diagnostic and staging workup includes high-quality computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography. Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis. However, histopathologic confirmation is not always required before resection. Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging. The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification. Selected patients with unresectable hCCA can be considered for liver transplantation. Adjuvant chemotherapy should be offered to patients with a high risk of recurrence. The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions. Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage. Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.


Bile Duct Neoplasms , Cholangiocarcinoma , Klatskin Tumor , Humans , Klatskin Tumor/therapy , Klatskin Tumor/surgery , Treatment Outcome , Hepatectomy/methods , Bile Duct Neoplasms/diagnosis , Bile Duct Neoplasms/therapy , Bile Duct Neoplasms/pathology , Cholangiocarcinoma/diagnosis , Cholangiocarcinoma/therapy , Bile Ducts, Intrahepatic/pathology , Cholangiopancreatography, Endoscopic Retrograde , Drainage
9.
World J Gastroenterol ; 30(13): 1836-1850, 2024 Apr 07.
Article En | MEDLINE | ID: mdl-38659478

The term hepatolithiasis describes the presence of biliary stones within the intrahepatic bile ducts, above the hilar confluence of the hepatic ducts. The disease is more prevalent in Asia, mainly owing to socioeconomic and dietary factors, as well as the prevalence of biliary parasites. In the last century, owing to migration, its global incidence has increased. The main pathophysiological mechanisms involve cholangitis, bile infection and biliary strictures, creating a self-sustaining cycle that perpetuates the disease, frequently characterised by recurrent episodes of bacterial infection referred to as syndrome of "recurrent pyogenic cholangitis". Furthermore, long-standing hepatolithiasis is a known risk factor for development of intrahepatic cholangiocarcinoma. Various classifications have aimed at providing useful insight of clinically relevant aspects and guidance for treatment. The management of symptomatic patients and those with complications can be complex, and relies upon a multidisciplinary team of hepatologists, endoscopists, interventional radiologists and hepatobiliary surgeons, with the main goal being to offer relief from the clinical presentations and prevent the development of more serious complications. This comprehensive review provides insight on various aspects of hepatolithiasis, with a focus on epidemiology, new evidence on pathophysiology, most important clinical aspects, different classification systems and contemporary management.


Bile Ducts, Intrahepatic , Humans , Risk Factors , Bile Ducts, Intrahepatic/pathology , Lithiasis/epidemiology , Lithiasis/therapy , Lithiasis/diagnosis , Prevalence , Treatment Outcome , Liver Diseases/epidemiology , Liver Diseases/therapy , Liver Diseases/diagnosis , Incidence , Cholangitis/epidemiology , Cholangitis/therapy , Cholangitis/diagnosis
10.
R I Med J (2013) ; 107(5): 43-48, 2024 May 02.
Article En | MEDLINE | ID: mdl-38687269

Cholangiocarcinoma (CCA) is a rare cancer of the bile duct epithelium, and in the last few decades its incidence rate has been increasing. It is associated with a high mortality rate due to late diagnosis and its aggressive nature. Many risk factors have been identified; some are more common in certain regions than others. CCA can be classified according to its anatomical location or macroscopic growth pattern, the latter being most helpful for imaging interpretation. Clinical features can vary from obstructive-like symptoms to nonspecific symptoms, such as weight loss and malaise. Imaging, specifically MRI/MRCP, is crucial in diagnosing CCA, staging, and treatment planning. Surgery with chemotherapy is the mainstay treatment option, and other palliative treatment options exist for those who have unresectable disease.


Bile Duct Neoplasms , Cholangiocarcinoma , Humans , Cholangiocarcinoma/epidemiology , Cholangiocarcinoma/diagnostic imaging , Cholangiocarcinoma/diagnosis , Cholangiocarcinoma/therapy , Bile Duct Neoplasms/epidemiology , Bile Duct Neoplasms/diagnostic imaging , Bile Duct Neoplasms/diagnosis , Bile Duct Neoplasms/therapy , Risk Factors , Magnetic Resonance Imaging , Bile Ducts, Intrahepatic/diagnostic imaging , Bile Ducts, Intrahepatic/pathology
11.
Pathol Res Pract ; 256: 155223, 2024 Apr.
Article En | MEDLINE | ID: mdl-38452587

Evidence suggests that long non-coding RNAs (lncRNAs) play a pivotal role in the carcinogenesis and progression of various human malignancies including gastrointestinal malignancies. This comprehensive review reports the functions and mechanisms of the lncRNA maternally expressed gene 3 (MEG3) involved in gastrointestinal malignancies. It summarizes its roles in mediating the regulation of cellular proliferation, apoptosis, migration, invasiveness, epithelial-to-mesenchymal transition, and drug resistance in several gastrointestinal cancers such as colorectal cancer, gall bladder cancer, pancreatic cancer, gastric cancer, esophageal cancer, cholangiocarcinoma, gastrointestinal stromal tumors and most importantly, hepatocellular carcinoma. In addition, the authors briefly highlight its implicated mechanistic role and interactions with different non-coding RNAs and oncogenic signaling cascades. This review presents the rationale for developing non coding RNA-based anticancer therapy via harnessing the power of MEG3 in gastrointestinal malignancies.


Bile Duct Neoplasms , Carcinoma, Hepatocellular , Liver Neoplasms , RNA, Long Noncoding , Stomach Neoplasms , Humans , Bile Duct Neoplasms/genetics , Bile Ducts, Intrahepatic/pathology , Carcinoma, Hepatocellular/pathology , Cell Proliferation/genetics , Liver Neoplasms/pathology , RNA, Long Noncoding/genetics , Stomach Neoplasms/genetics
12.
BMC Cancer ; 24(1): 358, 2024 Mar 20.
Article En | MEDLINE | ID: mdl-38509498

BACKGROUND: The prognostic significance of tumor burden score (TBS) in relation to carcinoembryonic antigen (CEA) has not been investigated among patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC). This study aimed to develop and validate a simplified model, a combination of TBS and CEA (CTC grade), for predicting the long-term outcomes of postoperative ICC patients. METHODS: Patients who underwent curative - intent resection of ICC between 2011 and 2019 were identified from a large multi - institutional database. The impact of TBS, CEA, and the CTC grade on overall survival (OS) and recurrence - free survival (RFS) was evaluated in both the derivation and validation cohorts. The receiver operating characteristic curve was utilized for assessing the predictive accuracy of the model. Subgroup analyses were performed across 8th TNM stage system stratified by CTC grade to assess the discriminatory capacity within the same TNM stage. RESULTS: A total of 812 patients were included in the derivation cohort and 266 patients in the validation cohort. Survival varied based on CEA (low: 36.7% vs. high: 9.0%) and TBS (low: 40.3% vs. high: 17.6%) in relation to 5 - year survival (both p < 0.001). As expected, patients with low CTC grade (i.e., low TBS/low CEA) were associated with the best OS as well as RFS, while high CTC grade (i.e., high TBS/high CEA) correlated to the worst outcomes. The model exhibited well performance in both the derivation cohort (area under the curve of 0.694) and the validation cohort (0.664). The predictive efficacy of the CTC grade system remains consistently stable across TNM stages I and III/IV. CONCLUSION: The CTC grade, a composite parameter derived from the combination of TBS and CEA levels, served as an easy - to - use tool and performed well in stratifying patients with ICC relative to OS and RFS.


Bile Duct Neoplasms , Cholangiocarcinoma , Humans , Hepatectomy , Carcinoembryonic Antigen , Tumor Burden , Cholangiocarcinoma/pathology , Prognosis , Bile Duct Neoplasms/pathology , Bile Ducts, Intrahepatic/pathology , Retrospective Studies
13.
Inn Med (Heidelb) ; 65(4): 347-356, 2024 Apr.
Article De | MEDLINE | ID: mdl-38498179

The etiology of primary sclerosing cholangitis (PSC) remains unclear, which explains in part the lack of a causal treatment. The differential diagnostic distinction from the even rarer immunoglobulin 4 (IgG4)-associated cholangitis (IAC) is becoming increasingly more successful. Advances in the understanding of different clinical courses, improvements in noninvasive diagnostics through modern magnetic resonance imaging (MRI) and the introduction of liver elastography have led to the development of improved prognostic models. The evidence for recommendations on medicinal (e.g., ursodeoxycholic acid) or endoscopic treatment (e.g., balloon dilatation and/or stent insertion) for PSC is still low. In contrast, the long-term results of liver transplantation in PSC patients are constantly improving. Due to the lack of highly sensitive and specific screening methods the early recognition of cholangiocellular carcinoma (CCC) as the most important complication is rarely successful. The continuous improvement of endoscopic retrograde cholangiopancreatography (ERCP) and direct cholangioscopy in combination with molecular biological and fluorescence in situ hybridization (FISH) analyses of bile duct tissue samples are promising for refined diagnostics. Due to the significantly increased risk of colorectal cancer, an annual colonoscopy is recommended in the presence of inflammatory bowel disease. Improvement of the early diagnostics of PSC and successful testing of new treatment strategies raise hope for a continuous improvement in the medical support of these complex patients.


Bile Duct Neoplasms , Cholangitis, Sclerosing , Humans , Cholangitis, Sclerosing/diagnosis , In Situ Hybridization, Fluorescence , Liver/pathology , Bile Ducts, Intrahepatic/pathology , Bile Duct Neoplasms/diagnosis
14.
Ann Clin Lab Sci ; 54(1): 106-111, 2024 Jan.
Article En | MEDLINE | ID: mdl-38514067

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a liver tumor with features of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). It consists of intermingled malignant biliary and hepatic tissue and thus a distinct entity, rather than two separate coexisting malignancies. A 59-year-old female with a history of hepatitis C and cirrhosis presented with abdominal pain and altered mental status. She developed hematemesis, and despite extensive interventions, she expired one day after her initial presentation. At autopsy, the liver was diffusely and markedly fibrotic with numerous nodules of varying size with invasion into adjacent vasculature. Microscopic examination of the nodules revealed cHCC-CC with stem cell features, lymphovascular invasion, and tumor emboli scattered throughout the right lung. The patient had end-stage liver disease due to the accumulation of damage and consequent fibrosis. This led to portal hypertension with subsequent massive gastrointestinal bleeding, hemorrhagic shock, and death. cHCC-CC is a rare, aggressive primary liver tumor with a poor prognosis. It can present with a cirrhotomemetic pattern with small nodules that can evade clinical and radiographic detection. Autopsy findings can provide valuable insights into the pathogenesis and clinical course of cHCC-CC, highlight the aggressive nature of the disease, and may inform future diagnostic and therapeutic strategies. Accurate diagnosis of this tumor is important for patient management and prognostication.


Bile Duct Neoplasms , Carcinoma, Hepatocellular , Cholangiocarcinoma , Liver Neoplasms , Humans , Female , Middle Aged , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Bile Ducts, Intrahepatic/pathology , Bile Duct Neoplasms/complications , Bile Duct Neoplasms/pathology , Cholangiocarcinoma/complications , Cholangiocarcinoma/pathology , Retrospective Studies
15.
Cancer Rep (Hoboken) ; 7(3): e2029, 2024 Mar.
Article En | MEDLINE | ID: mdl-38517409

BACKGROUND: Cholangiocarcinoma (CCA), as a rare malignancy of the biliary tree, has a poor prognosis most of the time. CCA is highly epigenetically regulated and several long non-coding RNAs (lncRNA) have been investigated to have a diagnostic and prognostic role in CCA. The current study aimed to assess the studies finding relevant lncRNAs in CCA systematically. METHODS: International databases, including PubMed, Cochrane Library, and Embase, were comprehensively searched in order to identify studies investigating any lncRNA in CCA. After screening by title/abstract and full-text, necessary data were extracted. Random-effect meta-analysis was performed for pooling the areas under the curve (AUCs), specificity, and sensitivity of lncRNAs for the diagnosis of CCA. RESULTS: A total of 33 studies were chosen to be included in the final analysis, comprised of 2677 patients. Meta-analysis of AUCs for evaluation of CCA resulted in pooled AUC of 0.79 (95% CI: 0.75-0.82; I2 = 69.11, p < .01). Additionally, overall sensitivity of 0.80 (95% CI 0.75-0.84) and specificity of 0.77 (95% CI: 0.68-0.84) were observed. Measurement of lncRANs in the assessment of CCA also improved overall survival significantly (effect size 1.61, 95% CI: 1.39-1.82). A similar result was found for progression-free survival (effect size 1.57, 95% CI: 1.20-1.93). CONCLUSION: Based on our findings, lncRNAs showed promising results as biomarkers in the diagnosis of CCA since they had acceptable sensitivity and specificity, in addition to the fact that improved survival in this poor prognosis cancer. Further studies might be needed to address this issue and find the best clinically useful lncRNA.


Bile Duct Neoplasms , Cholangiocarcinoma , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , Bile Duct Neoplasms/diagnosis , Bile Duct Neoplasms/genetics , Bile Duct Neoplasms/pathology , Cholangiocarcinoma/diagnosis , Cholangiocarcinoma/genetics , Cholangiocarcinoma/pathology , Sensitivity and Specificity , Bile Ducts, Intrahepatic/pathology
16.
Open Vet J ; 14(2): 664-673, 2024 Feb.
Article En | MEDLINE | ID: mdl-38549578

Background: Inflammation caused by Opisthorchis viverrini infection increases the risk of cholangitis, cholecystitis, and leads to bile duct cancer (cholangiocarcinoma or CCA). However, only certain infected individuals are susceptible to CCA, suggesting the involvement of host factors in cancer development. In addition, there are reports indicating differences in the locations of CCA. Aim: This study aims to investigate cellular inflammatory responses in the common bile duct (CB), intrahepatic bile duct (IHB), and gallbladder (GB) in susceptible and non-susceptible hosts following O. viverrini infection. Methods: Thirty Syrian golden hamsters (a susceptible host) and 30 BALB/c mice (a non-susceptible host) infected with O. viverrini were studied at six time points (five animals per group). Histopathological evaluations were conducted on samples from the IHB, CB, and GB. Inflammatory cell infiltration was quantitatively assessed and compared between groups and time points. Statistical analysis was performed using one-way ANOVA, with a significance level of p < 0.05. Results: Inflammation was significantly more pronounced in the IHB compared to the other two biliary locations. In comparison between susceptible and non-susceptible hosts, the intensity of inflammation was higher in the OV+H group than in the OV+M group (p < 0.05). Conclusion: This study highlights the association between host response to inflammation, tissue location, and host susceptibility, with the IHB showing particular susceptibility to inflammation and pathological changes. These findings contribute to our understanding of the increased risk of CCA in susceptible hosts.


Bile Duct Neoplasms , Cholangiocarcinoma , Opisthorchiasis , Opisthorchis , Rodent Diseases , Cricetinae , Mice , Animals , Opisthorchiasis/complications , Opisthorchiasis/pathology , Opisthorchiasis/veterinary , Opisthorchis/physiology , Bile Ducts, Intrahepatic/pathology , Mesocricetus , Cholangiocarcinoma/pathology , Cholangiocarcinoma/veterinary , Inflammation/veterinary , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/veterinary
17.
Acta Pharm ; 74(1): 1-36, 2024 Mar 01.
Article En | MEDLINE | ID: mdl-38554385

The arrival of comprehensive genome sequencing has accelerated the understanding of genetically aberrant advanced cancers and target identification for possible cancer treatment. Fibroblast growth factor receptor (FGFR) gene alterations are frequent findings in various rare and advanced cancers refractive to mainstay chemo-therapy or surgical interventions. Several FGFR inhibitors have been developed for addressing these genetically altered FGFR-harboring malignancies, and some have performed well in clinical trials. In contrast, others are still being investigated in different phases of clinical trials. FDA has approved four anticancer agents such as erdafitinib, pemigatinib, infigratinib, and futibatinib, for clinical use in oncogenic FGFR-driven malignancies. These include cholangiocarcinoma, urothelial carcinoma, and myeloid/lymphoid malignancies. Pemigatinib is the only FGFR inhibitor globally approved (USA, EU, and Japan) and available as a targeted therapy for two types of cancer, including FGFR2 fusion or other rearrangements harboring cholangiocarcinoma and relapsed/refractory myeloid/lymphoid neoplasms with FGFR1 rearrangements. Myeloid/lymphoid neoplasm is the latest area of application added to the therapeutic armamentarium of FGFR inhibitors. Furthermore, futibatinib is the first-in-class covalent or irreversible pan-FGFR inhibitor that has received FDA approval for locally advanced or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 gene aberrations. This review highlights the current clinical progress concerning the safety and efficacy of all the approved FGFR-TKIs (tyrosine kinase inhibitors) and their ongoing investigations in clinical trials for other oncogenic FGFR-driven malignancies.


Bile Duct Neoplasms , Carcinoma, Transitional Cell , Cholangiocarcinoma , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/drug therapy , Cholangiocarcinoma/drug therapy , Cholangiocarcinoma/genetics , Bile Ducts, Intrahepatic/pathology
18.
Eur J Surg Oncol ; 50(4): 108246, 2024 Apr.
Article En | MEDLINE | ID: mdl-38484491

BACKGROUND: Sarcopenia is associated with adverse prognosis of intrahepatic cholangiocarcinoma (iCCA) after surgery. METHODS: 321 patients with iCCA undergoing surgery were retrospectively recruited and assigned to training and validation cohort. Skeletal muscle index (SMI) was assessed to define sarcopenia. Logistic regression and cox regression analysis were used to identify risk factors. A novel sarcopenia-based nomogram was constructed and validated by ROC curves, calibration curves, and DCA curves. RESULTS: 260 patients were included for analysis. The median age was 63.0 years and 161 patients (61.9%) were diagnosed with sarcopenia. Patients with sarcopenia exhibited a higher rate of postoperative complications, a worse OS and RFS than patients without sarcopenia. Sarcopenia, low albumin and intraoperative blood transfusion were independent risk factors of postoperative complications, while sarcopenia and low albumin were risk factors of high CCI≥26.2. Sarcopenia, high PS score, low-undifferentiated differentiation, perineural invasion, TNM stage III-IV were risk factors of OS, and a novel nomogram based on these five factors was built to predict the 12-, 24-, and 36-months OS, with the mean AUC > 0.6. CONCLUSION: Sarcopenia is negatively associated with both postoperative complications and survival prognosis of iCCA undergoing hepatectomy.


Bile Duct Neoplasms , Cholangiocarcinoma , Sarcopenia , Humans , Middle Aged , Hepatectomy , Sarcopenia/complications , Sarcopenia/epidemiology , Retrospective Studies , Cholangiocarcinoma/complications , Cholangiocarcinoma/surgery , Prognosis , Bile Duct Neoplasms/complications , Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic/pathology , Postoperative Complications/pathology , Albumins
19.
Cancer Med ; 13(4): e6892, 2024 Feb.
Article En | MEDLINE | ID: mdl-38457226

BACKGROUND AND AIMS: Cholangiocarcinoma (CCA), a rare and aggressive hepatobiliary malignancy, presents significant clinical management challenges. Despite rising incidence and evolving treatment options, prognosis remains poor, motivating the exploration of real-world data for enhanced understanding and patient care. METHODS: This multicenter study analyzed data from 120 metastatic CCA patients at three institutions from 2016 to 2023. Kaplan-Meier curves assessed overall survival (OS), while univariate and multivariate analyses evaluated links between clinical variables (age, gender, tumor site, metastatic burden, ECOG performance status, response to first-line chemotherapy) and OS. Genetic profiling was conducted selectively. RESULTS: Enrolled patients had a median age of 68.5 years, with intrahepatic tumors predominant in 79 cases (65.8%). Among 85 patients treated with first-line chemotherapy, cisplatin and gemcitabine (41.1%) was the most common regimen. Notably, one-third received no systemic treatment. After a median 14-month follow-up, 81 CCA-related deaths occurred, with a median survival of 13.1 months. Two clinical variables independently predicted survival: response to first-line chemotherapy (disease control vs. no disease control; HR: 0.27; 95% CI: 0.14-0.50; p < 0.0001) and metastatic involvement (>1 site vs. 1 site; HR: 1.99; 95% CI: 1.04-3.80; p = 0.0366). The three most common genetic alterations involved the ARID1A, tp53, and CDKN2A genes. CONCLUSIONS: Advanced CCA displays aggressive clinical behavior, emphasizing the need for treatments beyond chemotherapy. Genetic diversity supports potential personalized therapies. Collaborative research and deeper CCA biology understanding are crucial to enhance patient outcomes in this challenging malignancy.


Bile Duct Neoplasms , Cholangiocarcinoma , Aged , Humans , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bile Duct Neoplasms/drug therapy , Bile Duct Neoplasms/genetics , Bile Ducts, Intrahepatic/pathology , Cholangiocarcinoma/drug therapy , Cholangiocarcinoma/genetics , Cholangiocarcinoma/pathology , Genetic Heterogeneity , Prognosis
20.
Phys Med ; 120: 103322, 2024 Apr.
Article En | MEDLINE | ID: mdl-38452430

PURPOSE: This study aimed to evaluate the ability of MRI-based intratumoral and peritumoral radiomics features of liver tumors to differentiate between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) and to predict ICC differentiation. METHODS: This study retrospectively collected 87 HCC patients and 75 ICC patients who were confirmed pathologically. The standard region of interest (ROI) of the lesion drawn by the radiologist manually shrank inward and expanded outward to form multiple ROI extended regions. A three-step feature selection method was used to select important radiomics features and convolution features from extended regions. The predictive performance of several machine learning classifiers on dominant feature sets was compared. The extended region performance was assessed by area under the curve (AUC), specificity, sensitivity, F1-score and accuracy. RESULTS: The performance of the model is further improved by incorporating convolution features. Compared with the standard ROI, the extended region obtained better prediction performance, among which 6 mm extended region had the best prediction ability (Classification: AUC = 0.96, F1-score = 0.94, Accuracy: 0.94; Grading: AUC = 0.94, F1-score = 0.93, Accuracy = 0.89). CONCLUSION: Larger extended region and fusion features can improve tumor predictive performance and have potential value in tumor radiology.


Bile Duct Neoplasms , Carcinoma, Hepatocellular , Cholangiocarcinoma , Liver Neoplasms , Humans , Liver Neoplasms/pathology , Retrospective Studies , Radiomics , Magnetic Resonance Imaging/methods , Bile Ducts, Intrahepatic/pathology
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