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Cancers May 2024Intraductal papillary mucinous neoplasms (IPMNs) are premalignant cystic neoplasms of the pancreas (CNPs), which can progress to invasive IPMN and pancreatic cancer. The...
Oncological Outcomes and Patterns of Recurrence after the Surgical Resection of an Invasive Intraductal Papillary Mucinous Neoplasm versus Primary Pancreatic Ductal Adenocarcinoma: An Analysis from the German Cancer Registry Group of the Society of German Tumor Centers.
BACKGROUND
Intraductal papillary mucinous neoplasms (IPMNs) are premalignant cystic neoplasms of the pancreas (CNPs), which can progress to invasive IPMN and pancreatic cancer. The available literature has shown controversial results regarding prognosis and clinical outcomes after the resection of invasive IPMN.
AIMS
This study aims to characterize the oncologic outcomes and metastatic progression pattern after the resection of non-metastatic invasive IPMN.
METHODS
Data were obtained from 24 clinical cancer registries participating in the German Cancer Registry Group of the Society of German Tumor Centers (ADT). Patients with invasive IPMN ( = 217) as well as PDAC ( = 5794) between 2000 and 2021 were included and compared regarding oncological outcomes.
RESULTS
Invasive IPMN was significantly smaller in size ( < 0.001) and of a lower tumor grade ( < 0.001), with fewer lymph node metastases ( < 0.001), lymphangiosis ( < 0.001), and consequently a higher R0 resection rate (88 vs. 74%) compared to PDAC. Moreover, invasive IPMN was associated with fewer local (11 vs. 15%) and distant recurrences (29 vs. 46%) and metastasized more frequently in the lungs only (26% vs. 14%). Invasive IPMN was associated with a longer median OS (29 vs. 19 months) and DFS (31 vs. 15 months) compared to PDAC and stayed independently prognostic in multivariable analyses. These survival differences were most pronounced in early tumor stages. Interestingly, postoperative chemotherapy was not associated with improved overall survival in surgically resected invasive IPMN.
CONCLUSIONS
Invasive IPMN is a rare pancreatic entity with increasing incidence in Germany. It is associated with favorable histopathological features at the time of resection and longer OS and DFS compared to PDAC, particularly before the locoregional spread has occurred. Invasive IPMNs are associated with lung-only metastasis. The benefit of postoperative chemotherapy after the resection of invasive IPMN remains uncertain.
PubMed: 38893136
DOI: 10.3390/cancers16112016 -
Clinical Epigenetics Jun 2024Papillary thyroid carcinoma (PTC) is a common endocrine malignancy. Studies have indicated that estrogen can regulate the expression of miRNAs in numerous malignancies....
BACKGROUND
Papillary thyroid carcinoma (PTC) is a common endocrine malignancy. Studies have indicated that estrogen can regulate the expression of miRNAs in numerous malignancies. MiR-570-3p has been shown to have a regulatory function in various cancers. However, studies of the regulatory function of miR-570-3p and a direct link between estrogen (especially estradiol E2) and miR-570-3p in PTC have not been done.
METHODS
Expression of miR-570-3p and its downstream target DPP4 in PTC tissues and cells was predicted using bioinformatics and validated by qRT-PCR and western blot assays. We then performed a series of gain-and-loss experiments to assess the functional significance of miR-570-3p/DPP4 axis in PTC progression in vitro and in vivo. Additionally, the methylation of the miR-570-3p promoter region was examined via bioinformatics analysis and MSP. Finally, the effects of E2 on PTC progression and the correlation between DNMT1/DNMT3A and EZH2 were predicted by bioinformatic tools and proved by luciferase reporter, ChIP, and co-IP assays.
RESULTS
In PTC tumor tissues and cell lines, there was a lower expression level and a higher methylation level of miR-570-3p compared to normal tissues and cell lines. DPP4 was identified as the downstream target of miR-570-3p. Overexpression of miR-570-3p reduced the proliferative, migratory, and invasive capabilities, and promoted apoptosis, while overexpression of DPP4 reversed these effects in PTC cells. It was also discovered that DNMT1 and DNMT3A increased the CpG methylation level of the miR-570-3p promoter in an EZH2-dependent manner, which led to decreased expression of miR-570-3p. Furthermore, we observed that estrogen (E2) enhanced the methylation of miR-570-3p and suppressed its expression levels, resulting in augmented tumor growth in vivo in PTC.
CONCLUSION
Estrogen regulates the EZH2/DNMTs/miR-570-3p/DPP4 signaling pathway to promote PTC progression.
Topics: Humans; MicroRNAs; DNA (Cytosine-5-)-Methyltransferase 1; Enhancer of Zeste Homolog 2 Protein; Thyroid Cancer, Papillary; Dipeptidyl Peptidase 4; DNA Methyltransferase 3A; Cell Line, Tumor; Thyroid Neoplasms; Estrogens; Gene Expression Regulation, Neoplastic; Female; Mice; DNA Methylation; Animals; DNA (Cytosine-5-)-Methyltransferases; Cell Proliferation; Male; Promoter Regions, Genetic
PubMed: 38890707
DOI: 10.1186/s13148-024-01685-z -
Pancreas Jul 2024Endoscopic ultrasound (EUS) is an excellent diagnostic tool that provides high-resolution images of pancreatic cystic lesions. However, its role in the diagnosis of...
OBJECTIVES
Endoscopic ultrasound (EUS) is an excellent diagnostic tool that provides high-resolution images of pancreatic cystic lesions. However, its role in the diagnosis of malignant intraductal papillary mucinous neoplasm (IPMN) remains limited and unclear. We aimed to determine the usefulness of this modality for such diagnosis.
METHODS
Overall, 246 patients who underwent EUS for IPMN after computed tomography (CT)/magnetic resonance imaging (MRI) from April 2018 to June 2021 were followed up until March 2022. We assessed the added value of performing EUS after CT or MRI for diagnosing malignant IPMN, using receiver operating characteristic curve analysis. Walls as thick as 2 mm were considered thickened in this study if they were highly uneven.
RESULTS
EUS clearly enhanced accuracy in identifying enhancing nodules and thickened walls. The areas under the receiver operating characteristic curve and corresponding 95% confidence intervals were 0.655 (0.549-0.760) and 0.566 (0.478-0.654) upon CT/MRI but 0.853 (0.763-0.942) and 0.725 (0.634-0.817) when observed using EUS. The combination of nodule size, thickened wall, and main duct size yielded the highest area under the receiver operating characteristic curve (0.944 [0.915-0.973]).
CONCLUSIONS
EUS more accurately detects malignant IPMN, as uneven wall thickening and certain nodules cannot be identified with CT/MRI.
Topics: Humans; Endosonography; Male; Female; Aged; Middle Aged; Magnetic Resonance Imaging; Tomography, X-Ray Computed; Pancreatic Neoplasms; Pancreatic Intraductal Neoplasms; ROC Curve; Carcinoma, Pancreatic Ductal; Adenocarcinoma, Mucinous; Aged, 80 and over; Retrospective Studies; Adult; Reproducibility of Results
PubMed: 38888840
DOI: 10.1097/MPA.0000000000002329 -
Frontiers in Endocrinology 2024The aim of this study was to develop a nomogram, using serum thymidine kinase 1 protein (STK1p) combined with ultrasonography parameters, to early predict central lymph...
Nomogram model of serum thymidine kinase 1 combined with ultrasonography for prediction of central lymph node metastasis risk in patients with papillary thyroid carcinoma pre-surgery.
OBJECTIVE
The aim of this study was to develop a nomogram, using serum thymidine kinase 1 protein (STK1p) combined with ultrasonography parameters, to early predict central lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC) pre-surgery.
METHODS
Patients with PTC pre-surgery in January 2021 to February 2023 were divided into three cohorts: the observation cohort (CLNM, = 140), the control cohort (NCLNM, = 128), and the external verification cohort (CLNM, = 50; NCLNM, = 50). STK1p was detected by an enzyme immunodot-blot chemiluminescence analyzer and clinical parameters were evaluated by ultrasonography.
RESULTS
A suitable risk threshold value for STK1p of 1.7 pmol/L was selected for predicting CLNM risk by receiver operating characteristic (ROC) curve analysis. Multivariate analysis identified the following six independent risk factors for CLNM: maximum tumor size >1 cm [odds ratio (OR) = 2.406, 95% confidence interval (CI) (1.279-4.526), = 0.006]; capsule invasion [OR = 2.664, 95% CI (1.324-5.360), = 0.006]; irregular margin [OR = 2.922; 95% CI (1.397-6.111), = 0.004]; CLN flow signal [OR = 3.618, 95% CI (1.631-8.027), = 0.002]; tumor-foci number ≥2 [OR = 4.064, 95% CI (2.102-7.859), < 0.001]; and STK1p ≥1.7 pmol/L [OR = 7.514, 95% CI (3.852-14.660), < 0.001]. The constructed nomogram showed that the area under the ROC curve for the main dataset was 0.867 and that for the validation dataset was 0.830, exhibiting effectivity, and was recalculated to a total score of approximately 383. Through monitoring the response post-surgery, all patients were assessed as tumor-free at 12 months post-surgery, which was significantly associated with a reduction in STK1p to disease-free levels.
CONCLUSION
We demonstrate for the first time that a novel nomogram including STK1p combined with ultrasonography can assist in the clinical prevention of CLNM, by facilitating timely, individualized prophylactic CLNM dissection, thereby reducing the risk of secondary surgery and the probability of recurrence.
Topics: Humans; Male; Female; Thymidine Kinase; Nomograms; Middle Aged; Lymphatic Metastasis; Adult; Thyroid Cancer, Papillary; Thyroid Neoplasms; Ultrasonography; Biomarkers, Tumor; Risk Factors; ROC Curve; Prognosis; Aged; Young Adult; Lymph Nodes
PubMed: 38887267
DOI: 10.3389/fendo.2024.1366219 -
Cancer Imaging : the Official... Jun 2024The aim of our study is to find a better way to identify a group of papillary thyroid carcinoma (PTC) with more aggressive behaviors and to provide a prediction model...
OBJECTIVE
The aim of our study is to find a better way to identify a group of papillary thyroid carcinoma (PTC) with more aggressive behaviors and to provide a prediction model for lymph node metastasis to assist in clinic practice.
METHODS
Targeted sequencing of DNA/RNA was used to detect genetic alterations. Gene expression level was measured by quantitative real-time PCR, western blotting or immunohistochemistry. CCK8, transwell assay and flow cytometry were used to investigate the effects of concomitant gene alterations in PTC. LASSO-logistics regression algorithm was used to construct a nomogram model integrating radiomic features, mutated genes and clinical characteristics.
RESULTS
172 high-risk variants and 7 fusion types were detected. The mutation frequencies in BRAF, TERT, RET, ATM and GGT1 were significantly higher in cancer tissues than benign nodules. Gene fusions were detected in 16 samples (2 at the DNA level and 14 at the RNA level). ATM mutation (ATM) was frequently accompanied by BRAF, TERT or gene fusions. ATM alone or ATM co-mutations were significantly positively correlated with lymph node metastasis. Accordingly, ATM knock-down PTC cells bearing BRAF, KRAS or CCDC6-RET had higher proliferative ability and more aggressive potency than cells without ATM knock-down in vitro. Furthermore, combining gene alterations and clinical features significantly improved the predictive efficacy for lymph node metastasis of radiomic features, from 71.5 to 87.0%.
CONCLUSIONS
Targeted sequencing of comprehensive genetic alterations in PTC has high prognostic value. These alterations, in combination with clinical and radiomic features, may aid in predicting invasive PTC with higher accuracy.
Topics: Humans; Lymphatic Metastasis; Thyroid Cancer, Papillary; Male; Female; Thyroid Neoplasms; Middle Aged; Mutation; Adult; Proto-Oncogene Proteins B-raf; Ataxia Telangiectasia Mutated Proteins; Nomograms; Biomarkers, Tumor; Telomerase; Radiomics
PubMed: 38886866
DOI: 10.1186/s40644-024-00719-2 -
BMC Gastroenterology Jun 2024Dilatation of common bile duct (CBD) is mostly pathological and mainly occurs secondary to mechanical causes. We aimed to explore the prevalence of CBD dilatation in...
BACKGROUND
Dilatation of common bile duct (CBD) is mostly pathological and mainly occurs secondary to mechanical causes. We aimed to explore the prevalence of CBD dilatation in Intraductal Papillary Mucinous Neoplasms of the pancreas (IPMN) among patients referred to EUS.
METHODS
A retrospective study of all patients who had an EUS diagnosis of IPMN from 2011 to 2019 at Galilee Medical Center were extracted. Control group including patients with other types of pancreatic cysts.
RESULTS
Overall, 2400 patients were included in the study, of them 158 patients were diagnosed with pancreatic cysts, 117 patients (74%) diagnosed with IPMN (group A), and 41 patients (26%) diagnosed with other pancreatic cysts (group B). Univariate analysis showed significant association of IPMN (OR 3.8, 95% CI 1.3-11.5), resected gallbladder (GB) (OR 7.75, 95% CI 3.19-18.84), and age (OR 1, 95% CI 1.01-1.08) with CBD dilatation. Classifying IPMN to sub-groups using adjusted multivariate logistic regression analysis, only main duct-IPMN (MD-IPMN) significantly correlated with CBD dilatation compared to branch duct (BD)-IPMN and mixed type-IPMN (OR 19.6, 95% CI 4.57-83.33, OR 16.3, 95% CI 3.02-88.08).
CONCLUSION
MD-IPMN was significantly correlated with dilated CBD. Assessment of the pancreas is warranted in encountered cases of dilated CBD without obvious mechanical cause.
Topics: Humans; Male; Female; Retrospective Studies; Middle Aged; Dilatation, Pathologic; Aged; Common Bile Duct; Pancreatic Intraductal Neoplasms; Endosonography; Pancreatic Cyst; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Adenocarcinoma, Mucinous
PubMed: 38886637
DOI: 10.1186/s12876-024-03291-y -
Journal of Thoracic Disease May 2024The preoperative differential diagnosis of nodular lung adenocarcinoma has long been a challenging issue for thoracic surgeons. This study aimed to explore differential...
BACKGROUND
The preoperative differential diagnosis of nodular lung adenocarcinoma has long been a challenging issue for thoracic surgeons. This study aimed to explore differential diagnosis of nodular lung adenocarcinoma by comprehensively analyzing its clinical, computed tomography (CT) imaging, and postoperative pathological and genetic features.
METHODS
The clinical, CT imaging, and postoperative pathological features of different classifications of nodular lung adenocarcinoma were retrospectively analyzed through univariate and multivariate statistical methods.
RESULTS
There were 132 patients with nodular lung adenocarcinoma enrolled. Firstly, compared with ground-glass nodular lung adenocarcinoma, solid nodular lung adenocarcinoma was more common in women [odds ratio (OR), 3.662; 95% confidence interval (CI): 1.066-12.577] and older adults (OR, 1.061; 95% CI: 1.007-1.119), and CT signs were mostly lobulation (OR, 4.957; 95% CI: 1.714-14.337) and spiculation (OR, 8.214; 95% CI: 2.740-24.621); the mean CT (CT) value of solid nodular lung adenocarcinoma was significantly higher than that of ground-glass nodular lung adenocarcinoma, and the optimal diagnostic threshold was -267.5 Hounsfield units (HU). Secondly, the maximum diameter of nodule size (NS) of invasive adenocarcinoma (IAC) was significantly greater than that of minimally IAC (MIA; OR, 6.306; 95% CI: 1.191-33.400) or atypical adenomatous hyperplasia (AAH)/adenocarcinoma in situ (AIS; OR, 189.539; 95% CI: 4.720-7,610.476), and the optimal diagnostic threshold between IAC and MIA was 1.35 cm; the CT value of IAC was significantly higher than that of MIA, and the optimal diagnostic threshold was -460.75 HU. Thirdly, lepidic-predominant adenocarcinoma (LPA) manifest more commonly as pure ground-glass nodule (pGGN; OR, 6.252; 95% CI: 1.429-27.358) or mixed ground-glass nodule (mGGN; OR, 4.224; 95% CI: 1.223-14.585). Moreover, the mutation rate of epidermal growth factor receptor () in IAC was 70.69% (41/58). The mutation rates of mGGNs (OR, 8.794; 95% CI: 1.489-51.933) and solid nodules (SNs; OR, 12.912; 95% CI: 1.597-104.383) were significantly higher than that of pGGNs. Furthermore, compared with those of micropapillary-predominant adenocarcinoma (MPA), solid-predominant adenocarcinoma (SPA), or invasive mucinous adenocarcinoma (IMA), there were significantly higher mutation rates in acinar-predominant adenocarcinoma/papillary-predominant adenocarcinoma (APA/PPA; OR, 55.925; 95% CI: 4.045-773.284) and LPA (OR, 38.265; 95% CI: 2.307-634.596).
CONCLUSIONS
Different classifications of nodular lung adenocarcinoma have their own clinicopathological and CT imaging features, and the latter is the main predictor.
PubMed: 38883620
DOI: 10.21037/jtd-24-510 -
Frontiers in Endocrinology 2024The mucosa-associated lymphoid tissue (MALT) lymphoma subtype, specifically extranodal marginal zone B-cell lymphoma, is a rare variant. Within this subtype, primary...
The mucosa-associated lymphoid tissue (MALT) lymphoma subtype, specifically extranodal marginal zone B-cell lymphoma, is a rare variant. Within this subtype, primary thyroid MALT lymphoma is an uncommon occurrence. The literature provides limited documentation on thyroid MALT lymphomas, as their prevalence is comparatively lower than in other organ sites. The coexistence of papillary thyroid carcinoma (PTC) and thyroid MALT lymphomas is exceedingly rare. It presents a rare case of primary thyroid MALT lymphoma accompanied by PTC, thyroid lymphoma not being considered before surgery. A 64-year-old female patient, who had been experiencing symptoms related to a substantial thyroid tumor for a duration of three years, she refused to do a needle biopsy before surgery and expressed a preference for surgical resection. Consequently, the patient underwent a total thyroidectomy along with lymphadenectomy of the central compartment. A histological examination subsequently confirmed the presence of papillary thyroid carcinoma (PTC) and mucosa-associated lymphoid tissue (MALT) lymphoma. Due to the favorable response of the MALT lymphoma to local treatment and the absence of metastasis in other organs, no further treatment was administered for the MALT lymphoma following the surgery. Currently, the patient exhibits no signs of tumor recurrence based on ultrasound and laboratory evaluations. We also provide an overview of the clinical findings on PTC and MALT lymphoma patients already reported and discuss the possible treatment strategy.
Topics: Humans; Lymphoma, B-Cell, Marginal Zone; Female; Middle Aged; Thyroid Neoplasms; Thyroid Cancer, Papillary; Thyroidectomy; Neoplasms, Multiple Primary
PubMed: 38883595
DOI: 10.3389/fendo.2024.1372661 -
Cancer Control : Journal of the Moffitt... 2024Cervical lymph node metastasis (CLNM) is considered a marker of papillar Fethicy thyroid cancer (PTC) progression and has a potential impact on the prognosis of PTC. The...
BACKGROUND AND OBJECTIVE
Cervical lymph node metastasis (CLNM) is considered a marker of papillar Fethicy thyroid cancer (PTC) progression and has a potential impact on the prognosis of PTC. The purpose of this study was to screen for predictors of CLNM in PTC and to construct a predictive model to guide the surgical approach in patients with PTC.
METHODS
This is a retrospective study. Preoperative dual-energy computed tomography images of 114 patients with pathologically confirmed PTC between July 2019 and April 2023 were retrospectively analyzed. The dual-energy computed tomography parameters [iodine concentration (IC), normalized iodine concentration (NIC), the slope of energy spectrum curve (λ)] of the venous stage cancer foci were measured and calculated. The independent influencing factors for predicting CLNM were determined by univariate and multivariate logistic regression analysis, and the prediction models were constructed. The clinical benefits of the model were evaluated using decision curves, calibration curves, and receiver operating characteristic curves.
RESULTS
The statistical results show that NIC, derived neutrophil-to-lymphocyte ratio (dNLR), prognostic nutritional index (PNI), gender, and tumor diameter were independent predictors of CLNM in PTC. The AUC of the nomogram was .898 (95% CI: .829-.966), and the calibration curve and decision curve showed that the prediction model had good predictive effect and clinical benefit, respectively.
CONCLUSION
The nomogram constructed based on dual-energy CT parameters and inflammatory prognostic indicators has high clinical value in predicting CLNM in PTC patients.
Topics: Humans; Male; Female; Lymphatic Metastasis; Thyroid Cancer, Papillary; Middle Aged; Retrospective Studies; Tomography, X-Ray Computed; Adult; Thyroid Neoplasms; Nomograms; Neck; Lymph Nodes; Prognosis; Aged; Inflammation
PubMed: 38881040
DOI: 10.1177/10732748241262177 -
Zhonghua Zhong Liu Za Zhi [Chinese... Jun 2024To analyze the location, discovery time and possible causes of cases of cervical cystic lymph node metastasis with an unknown primary misdiagnosed as branchial cleft...
To analyze the location, discovery time and possible causes of cases of cervical cystic lymph node metastasis with an unknown primary misdiagnosed as branchial cleft carcinoma. A retrospective analysis was performed on clinical and pathological data of 15 patients misdiagnosed as branchiogenic carcinoma at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2000 and December 2020. Among the 15 patients, 6 were nasopharyngeal squamous cell carcinoma, 4 tonsil squamous cell carcinoma, 2 tongue root squamous cell carcinoma, 2 hypopharyngeal squamous cell carcinoma and 1 thyroid papillary carcinoma. The median time from the diagnosis of branchial cleft carcinoma to the discovery of primary lesions was 3.58 months (0-76 months). The causes of misdiagnosis might be the lack of experience in the diagnosis and treatment of branchial cleft carcinoma, and not enough attention to comprehensive examination and close follow-up. Different from oropharyngeal cancer reported internationally, the proportion of misdiagnosed cases with nasopharyngeal carcinoma as the primary site in the current article is higher. As a country with a high incidence of nasopharyngeal carcinoma, the examination of nasopharynx should not be taken lightly. Most hidden cases can be found in the comprehensive examination in a short time, while a few cases need long-term follow-up. Finding the primary sites should not rely too much on imaging examination, and we cannot ignore the importance of clinical physical examination.
Topics: Humans; Lymphatic Metastasis; Retrospective Studies; Diagnostic Errors; Neoplasms, Unknown Primary; Branchioma; Nasopharyngeal Neoplasms; Female; Male; Middle Aged; Adult; Lymph Nodes; Neck; Thyroid Cancer, Papillary; Nasopharyngeal Carcinoma; Head and Neck Neoplasms; Tonsillar Neoplasms; Aged; Tongue Neoplasms; Hypopharyngeal Neoplasms
PubMed: 38880737
DOI: 10.3760/cma.j.cn112152-20231024-00248