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Molecular Cancer Research : MCR Jun 2024The pathogenesis of duodenal tumors in the inherited tumor syndromes familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) is poorly understood. This...
UNLABELLED
The pathogenesis of duodenal tumors in the inherited tumor syndromes familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) is poorly understood. This study aimed to identify genes that are significantly mutated in these tumors and to explore the effects of these mutations. Whole exome and whole transcriptome sequencing identified recurrent somatic coding variants of phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIGA) in 19/70 (27%) FAP and MAP duodenal adenomas, and further confirmed the established driver roles for APC and KRAS. PIGA catalyzes the first step in glycosylphosphatidylinositol (GPI) anchor biosynthesis. Flow cytometry of PIGA-mutant adenoma-derived and CRISPR-edited duodenal organoids confirmed loss of GPI anchors in duodenal epithelial cells and transcriptional profiling of duodenal adenomas revealed transcriptional signatures associated with loss of PIGA.
IMPLICATIONS
PIGA somatic mutation in duodenal tumors from patients with FAP and MAP and loss of membrane GPI-anchors may present new opportunities for understanding and intervention in duodenal tumorigenesis.
Topics: Humans; Glycosylphosphatidylinositols; Duodenal Neoplasms; Mutation; Adenomatous Polyposis Coli; Membrane Proteins; Carcinogenesis; Male; Female
PubMed: 38546397
DOI: 10.1158/1541-7786.MCR-23-0810 -
Dermatopathology (Basel, Switzerland) Mar 2024This case report describes a case of a patient with MUTYH-associated polyposis (MAP), who presented with multiple sebaceomas in a Muir-Torre-like phenotype. MAP is...
This case report describes a case of a patient with MUTYH-associated polyposis (MAP), who presented with multiple sebaceomas in a Muir-Torre-like phenotype. MAP is caused by mutations in MUTYH, a base excision repair gene responsible for detecting and repairing the 8-oxo-G:A transversion caused by reactive oxygen species. MAP is associated with an increased risk of developing adenomatous polyps and colorectal cancer. Muir-Torre syndrome is a clinical phenotype of Lynch syndrome, which presents with multiple cutaneous sebaceous neoplasms. Lynch syndrome, like MAP, increases the likelihood of developing colorectal cancer but with a different pathogenesis and mode of inheritance. This case demonstrates that in a patient presenting with multiple sebaceous neoplasms, further workup and genetic testing may be indicated, not only for Muir-Torre and Lynch syndrome but also for MAP.
PubMed: 38534264
DOI: 10.3390/dermatopathology11010011 -
Cancer Letters May 2024Familial adenomatous polyposis (FAP) is a heritable disease that increases the risk of colorectal cancer (CRC) development because of heterozygous mutations in APC....
Familial adenomatous polyposis (FAP) is a heritable disease that increases the risk of colorectal cancer (CRC) development because of heterozygous mutations in APC. Little is known about the microenvironment of FAP. Here, single-cell RNA sequencing was performed on matched normal tissues, adenomas, and carcinomas from four patients with FAP. We analyzed the transcriptomes of 56,225 unsorted single cells, revealing the heterogeneity of each cell type, and compared gene expression among tissues. Then we compared the gene expression with that of sporadic CRC. Furthermore, we analyzed specimens of 26 FAP patients and 40 sporadic CRC patients by immunohistochemistry. Immunosuppressiveness of myeloid cells, fibroblasts, and regulatory T cells was upregulated even in the early stages of carcinogenesis. CD8 T cells became exhausted only in carcinoma, although the cytotoxicity of CD8 T cells was gradually increased according to the carcinogenic step. When compared with those in the sporadic CRC microenvironment, the composition and function of each cell type in the FAP-derived CRC microenvironment had differences. Our findings indicate that an immunosuppressive microenvironment is constructed from a precancerous stage in FAP.
Topics: Humans; CD8-Positive T-Lymphocytes; Adenomatous Polyposis Coli; Adenomatous Polyposis Coli Protein; Adenoma; Carcinogenesis; Colorectal Neoplasms; Tumor Microenvironment
PubMed: 38521200
DOI: 10.1016/j.canlet.2024.216822 -
Computer Assisted Surgery (Abingdon,... Dec 2024The aim of this study is to analyze the risk factors associated with the development of adenomatous and malignant polyps in the gallbladder. Adenomatous polyps of the...
The aim of this study is to analyze the risk factors associated with the development of adenomatous and malignant polyps in the gallbladder. Adenomatous polyps of the gallbladder are considered precancerous and have a high likelihood of progressing into malignancy. Preoperatively, distinguishing between benign gallbladder polyps, adenomatous polyps, and malignant polyps is challenging. Therefore, the objective is to develop a neural network model that utilizes these risk factors to accurately predict the nature of polyps. This predictive model can be employed to differentiate the nature of polyps before surgery, enhancing diagnostic accuracy. A retrospective study was done on patients who had cholecystectomy surgeries at the Department of Hepatobiliary Surgery of the Second People's Hospital of Shenzhen between January 2017 and December 2022. The patients' clinical characteristics, lab results, and ultrasonographic indices were examined. Using risk variables for the growth of adenomatous and malignant polyps in the gallbladder, a neural network model for predicting the kind of polyps will be created. A normalized confusion matrix, PR, and ROC curve were used to evaluate the performance of the model. In this comprehensive study, we meticulously analyzed a total of 287 cases of benign gallbladder polyps, 15 cases of adenomatous polyps, and 27 cases of malignant polyps. The data analysis revealed several significant findings. Specifically, hepatitis B core antibody (95% CI -0.237 to 0.061, < 0.001), number of polyps (95% CI -0.214 to -0.052, = 0.001), polyp size (95% CI 0.038 to 0.051, < 0.001), wall thickness (95% CI 0.042 to 0.081, < 0.001), and gallbladder size (95% CI 0.185 to 0.367, < 0.001) emerged as independent predictors for gallbladder adenomatous polyps and malignant polyps. Based on these significant findings, we developed a predictive classification model for gallbladder polyps, represented as follows, Predictive classification model for GBPs = -0.149 * core antibody - 0.033 * number of polyps + 0.045 * polyp size + 0.061 * wall thickness + 0.276 * gallbladder size - 4.313. To assess the predictive efficiency of the model, we employed precision-recall (PR) and receiver operating characteristic (ROC) curves. The area under the curve (AUC) for the prediction model was 0.945 and 0.930, respectively, indicating excellent predictive capability. We determined that a polyp size of 10 mm served as the optimal cutoff value for diagnosing gallbladder adenoma, with a sensitivity of 81.5% and specificity of 60.0%. For the diagnosis of gallbladder cancer, the sensitivity and specificity were 81.5% and 92.5%, respectively. These findings highlight the potential of our predictive model and provide valuable insights into accurate diagnosis and risk assessment for gallbladder polyps. We identified several risk factors associated with the development of adenomatous and malignant polyps in the gallbladder, including hepatitis B core antibodies, polyp number, polyp size, wall thickness, and gallbladder size. To address the need for accurate prediction, we introduced a novel neural network learning algorithm. This algorithm utilizes the aforementioned risk factors to predict the nature of gallbladder polyps. By accurately identifying the nature of these polyps, our model can assist patients in making informed decisions regarding their treatment and management strategies. This innovative approach aims to improve patient outcomes and enhance the overall effectiveness of care.
Topics: Humans; Retrospective Studies; Gallbladder Neoplasms; Risk Factors; Polyps; Adenoma; Neural Networks, Computer; Adenomatous Polyps; Hepatitis B
PubMed: 38520294
DOI: 10.1080/24699322.2024.2331774 -
Spectrochimica Acta. Part A, Molecular... May 2024Colorectal cancer is the third most common malignancy worldwide and one of the leading causes of death in oncological patients with its diagnosis typically involving...
Colorectal cancer is the third most common malignancy worldwide and one of the leading causes of death in oncological patients with its diagnosis typically involving confirmation by tissue biopsy. In vivo Raman spectroscopy, an experimental diagnostic method less invasive than a biopsy, has shown great potential to discriminate between normal and cancerous tissue. However, the complex and often manual processing of Raman spectra along with the absence of a suitable instant classifier are the main obstacles to its adoption in clinical practice. This study aims to address these issues by developing a real-time automated classification pipeline coupled with a user-friendly application tailored for non-spectroscopists. First, in addition to routine colonoscopy, 377 subjects underwent in vivo acquisitions of Raman spectra of healthy tissue, adenomatous polyps, or cancerous tissue, which were conducted using a custom-made microprobe. The spectra were then loaded into the pipeline and pre-processed in several steps, including standard normal variate transformation and finite impulse response filtration. The quality of the pre-processed spectral data was checked based on their signal-to-noise ratio before the suitable spectra were decomposed and classified using a combination of principal component analysis and a support vector machine, respectively. After five-fold cross-validation, the developed classifier exhibited 100% sensitivity toward adenocarcinoma and adenomatous polyps. The overall accuracy was 96.9% and 79.2% for adenocarcinoma and adenomatous polyps respectively. In addition, an application with a graphical user interface was developed to facilitate the use of our data pipeline by medical professionals in a clinical environment. Overall, the combination of supervised and unsupervised machine learning with algorithmic pre-processing of in vivo Raman spectra appears to be a viable way of reducing the relatively large number of biopsies currently needed to definitively diagnose colorectal cancer.
Topics: Humans; Spectrum Analysis, Raman; Colonoscopy; Adenomatous Polyps; Adenocarcinoma; Colorectal Neoplasms
PubMed: 38503254
DOI: 10.1016/j.saa.2024.124152 -
Gan To Kagaku Ryoho. Cancer &... Mar 2024This retrospective study was performed to investigate the recent trend of occurrence of cancer of the remnant colorectal segment(RCRS)after ileal-pouch anal...
PURPOSE
This retrospective study was performed to investigate the recent trend of occurrence of cancer of the remnant colorectal segment(RCRS)after ileal-pouch anal anastomosis(IPAA)/ileorectal anastomosis(IRA)and to consider the optimal surveillance methods in patients with familial adenomatous polyposis(FAP)undergoing(procto)colectomy.
PATIENTS AND METHODS
The subject was a total of patients with FAP undergoing IPAA or IRA between 2005 and 2022. Clinicopathological data were extracted from medical charts and analyzed. Cumulative incidence of cancer in the RCRS and overall survival after treatment of such tumors were calculated by the Kaplan-Meier method.
RESULTS
There were 45 male and 56 female. IPAA was performed in 49 patients(hand-sewn; n=33, stapled; n=16)and IRA was performed in 52 patients. The median age at initial colorectal surgery was 32 years old(range, 13-66 years old). Median postoperative follow-up was 11 years(range, 1-48 years). Eighty-one patients were confirmed to have pathogenic variant of APC by genetic test. The cumulative incidence of cancer of the RCRS did not differ between patients undergoing IPAA and those undergoing IRA(p= 0.73, 4.1% versus 1.9% at 10 years). The cumulative 5-year overall survival rate after additional surgery for the tumor of RCRS was 82%.
CONCLUSION
This study has several limitations due to single institutional retrospective study with small cases and non-standardized postoperative endoscopic surveillance. However, our results seem to show satisfactory oncological outcomes of patients with FAP in terms of the control of cancer of the RCRS under postoperative periodic surveillance, regardless of the type of colorectal resection.
Topics: Humans; Male; Female; Adolescent; Young Adult; Adult; Middle Aged; Aged; Retrospective Studies; Ileum; Adenomatous Polyposis Coli; Anastomosis, Surgical; Neoplasms
PubMed: 38494824
DOI: No ID Found -
Gan To Kagaku Ryoho. Cancer &... Mar 2024Desmoid-type fibromatosis is a relatively rare disease, often associated with familial adenomatous polyposis and a history of abdominal surgery. A 43-year-old male...
Desmoid-type fibromatosis is a relatively rare disease, often associated with familial adenomatous polyposis and a history of abdominal surgery. A 43-year-old male patient presented with abdominal pain and contrast-enhanced CT showed a mass in the lower abdomen. The mass was a 4×4×3 cm white, dense tumor with a wreath-like arrangement of eosinophilic spindle-shaped cells. Immunostaining showed KIT(-), CD34(-), desmin(-), β-catenin(+), SMA(few+), and the diagnosis was desmoid-type fibrosis. Six months after surgery, there was no apparent recurrence.
Topics: Male; Humans; Adult; Fibromatosis, Aggressive; Adenomatous Polyposis Coli; Mesentery; Abdominal Pain; Intestine, Small; Fibromatosis, Abdominal
PubMed: 38494823
DOI: No ID Found -
Frontiers in Oncology 2024Pancreatoblastoma (PB) is a rare malignant pancreatic epithelial tumor that mostly occurs in children and occasionally occurs in adults. The tumor has acinar cell...
Pancreatoblastoma (PB) is a rare malignant pancreatic epithelial tumor that mostly occurs in children and occasionally occurs in adults. The tumor has acinar cell differentiation and squamous corpuscles/squamous epithelial islands, which are frequently separated by fibrous bundles. Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease characterized by the presence of numerous adenomatous polyps in the colon and rectum. Cases of pancreatoblastoma combined with familial adenomatous polyposis (FAP) are rarely reported. A review of a rare case of adult pancreatoblastoma with atypical histological morphology combined with familial adenomatous polyposis is presented herein. In this case, the patient was first diagnosed with familial adenomatous polyposis and subsequently found to have pancreatoblastoma 1 year and 3 months later. This suggests pancreatoblastoma may occur in patients with familial adenomatous polyposis or a family history of the condition, indicating a possible association between the two tumors. Therefore, pancreatoblastoma should be included in a differential diagnosis for FAP patients with a pancreatic mass. The final diagnosis of pancreatoblastoma depends on the pathological diagnosis. Acinar-like cells and squamous corpuscles/squamous epithelial cell islands under light microscopy are the key diagnostic points. This case report also can improve the awareness of clinicians, radiologists, and pathologists on the presence of rare tumor-adult pancreatoblastoma in patients with familial adenomatous polyposis.
PubMed: 38482206
DOI: 10.3389/fonc.2024.1346964 -
Computers in Biology and Medicine Apr 2024Early detection of colon adenomatous polyps is pivotal in reducing colon cancer risk. In this context, accurately distinguishing between adenomatous polyp subtypes,...
Early detection of colon adenomatous polyps is pivotal in reducing colon cancer risk. In this context, accurately distinguishing between adenomatous polyp subtypes, especially tubular and tubulovillous, from hyperplastic variants is crucial. This study introduces a cutting-edge computer-aided diagnosis system optimized for this task. Our system employs advanced Supervised Contrastive learning to ensure precise classification of colon histopathology images. Significantly, we have integrated the Big Transfer model, which has gained prominence for its exemplary adaptability to visual tasks in medical imaging. Our novel approach discerns between in-class and out-of-class images, thereby elevating its discriminatory power for polyp subtypes. We validated our system using two datasets: a specially curated one and the publicly accessible UniToPatho dataset. The results reveal that our model markedly surpasses traditional deep convolutional neural networks, registering classification accuracies of 87.1% and 70.3% for the custom and UniToPatho datasets, respectively. Such results emphasize the transformative potential of our model in polyp classification endeavors.
Topics: Humans; Colonic Polyps; Adenomatous Polyps; Neural Networks, Computer; Diagnosis, Computer-Assisted; Diagnostic Imaging
PubMed: 38479197
DOI: 10.1016/j.compbiomed.2024.108267 -
Annali Italiani Di Chirurgia 2024This purpose aims to investigate the usefulness of CD133, a stem cell marker, for the prognosis of colon polyps. This study aimed to assess the adenomatous polyps that...
BACKGROUND
This purpose aims to investigate the usefulness of CD133, a stem cell marker, for the prognosis of colon polyps. This study aimed to assess the adenomatous polyps that have an essential role in the development of colorectal cancer. The risk of colorectal carcinogenesis can be reduced by polypectomy and close medical supervision of the patients with adenomatous polyps. The prominence of stem cells in carcinoma development is also a recognized verdict. It must be noted that stem cell evaluation in adenomatous polyps may provide information about carcinoma development.
METHOD
Previously pathologically assessed colorectal polyps in 60 males and 40 females at Azerbaijan Medical University were reevaluated at the Pathology Department under the Meram Medical Faculty. Hematoxylin-eosin stained preparations were examined, and cases with and without dysplasia were determined. The image analysis program re-examined the preparations, and the same image analysis system automatically counted CD133 positive stained cells in the unit area. At the end of the follow-up period after polypectomy, the cases of malignancy were detected.
RESULTS
The relationship between CD133 expression of dysplasia and malignancy was statistically compared. During the investigation, the statistically significant relationship between CD133 expression and dysplasia, as well as malignancy development, was observed in this study.
CONCLUSION
During the examination, the statistical significance of CD133 expression was detected in cases with dysplasia and malignancy. The investigation of CD133 expression in colorectal polyps is crucial in determining the presence of dysplasia and malignancy development, particularly in obtaining prognostic data in colorectal polyps.
Topics: Male; Female; Humans; Colonic Polyps; Colorectal Neoplasms; Prognosis; Adenomatous Polyps; Neoplastic Stem Cells; Carcinoma; Colonoscopy
PubMed: 38469604
DOI: No ID Found