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1.
Dtsch Med Wochenschr ; 149(15): 887-893, 2024 Aug.
Article in German | MEDLINE | ID: mdl-39013409

ABSTRACT

Neuroendocrine neoplasms are classified according to the WHO classification based on morphological criteria into neuroendocrine tumors, neuroendocrine carcinomas, and mixed neuroendocrine-non-neuroendocrine neoplasms. Neuroendocrine tumors are well differentiated neoplasms and show characteristic site-specific histological and molecular features, which is important for their clinical management. In cases dealing with metastasis, pathology often can help to identify the primary tumors using a small immunohistochemical marker panel. Neuroendocrine carcinomas are poorly differentiated neoplasms. They are subdivided into neuroendocrine carcinomas of small cell and large cell type. The molecular profile of neuroendocrine carcinomas and mixed neuroendocrine-non-neuroendocrine neoplasms shows a close relationship to conventional adenocarcinomas with site-specific features. Molecular analysis of neuroendocrine carcinomas and neuroendocrine-non-neuroendocrine neoplasms are not yet fully integrated in daily diagnostics and are mainly performed in the context of precision oncology.


Subject(s)
Neuroendocrine Tumors , Pancreatic Neoplasms , Humans , Biomarkers, Tumor/genetics , Intestinal Neoplasms/pathology , Intestinal Neoplasms/genetics , Neuroendocrine Tumors/genetics , Neuroendocrine Tumors/pathology , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology
2.
Front Endocrinol (Lausanne) ; 15: 1385079, 2024.
Article in English | MEDLINE | ID: mdl-38948517

ABSTRACT

Background: 177Lu-oxodotreotide peptide receptor therapy (LuPRRT) is an efficient treatment for midgut neuroendocrine tumors (NETs) of variable radiological response. Several clinical, biological, and imaging parameters may be used to establish a relative disease prognosis but none is able to predict early efficacy or toxicities. We investigated expression levels for mRNA and miRNA involved in radiosensitivity and tumor progression searching for correlations related to patient outcome during LuPRRT therapy. Methods: Thirty-five patients received LuPRRT for G1/G2 midgut NETs between May 2019 and September 2021. Peripheral blood samples were collected prior to irradiation, before and 48 h after the second and the fourth LuPRRT, and at 6-month follow-up. Multiple regression analyses and Pearson correlations were performed to identify the miRNA/mRNA signature that will best predict response to LuPRRT. Results: Focusing on four mRNAs and three miRNAs, we identified a miRNA/mRNA signature enabling the early identification of responders to LuPRRT with significant reduced miRNA/mRNA expression after the first LuPRRT administration for patients with progressive disease at 1 year (p < 0.001). The relevance of this signature was reinforced by studying its evolution up to 6 months post-LuPRRT. Moreover, nadir absolute lymphocyte count within the first 2 months after the first LuPRRT administration was significantly related to low miRNA/mRNA expression level (p < 0.05) for patients with progressive disease. Conclusion: We present a pilot study exploring a miRNA/mRNA signature that correlates with early hematologic toxicity and therapeutic response 12 months following LuPRRT. This signature will be tested prospectively in a larger series of patients.


Subject(s)
Intestinal Neoplasms , MicroRNAs , Neuroendocrine Tumors , RNA, Messenger , Humans , Neuroendocrine Tumors/genetics , Neuroendocrine Tumors/blood , Neuroendocrine Tumors/therapy , Neuroendocrine Tumors/radiotherapy , Neuroendocrine Tumors/pathology , Male , Female , MicroRNAs/blood , MicroRNAs/genetics , Middle Aged , Intestinal Neoplasms/blood , Intestinal Neoplasms/pathology , Intestinal Neoplasms/genetics , Intestinal Neoplasms/drug therapy , RNA, Messenger/genetics , RNA, Messenger/blood , Aged , Follow-Up Studies , Adult , Prognosis , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Somatostatin/analogs & derivatives , Somatostatin/therapeutic use , Receptors, Peptide/genetics , Radiopharmaceuticals/therapeutic use , Radiopharmaceuticals/administration & dosage , Lutetium , Radioisotopes
3.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(3): 458-461, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-38953271

ABSTRACT

Intestinal mantle cell lymphoma complicated with intussusception is rare in clinical practice,lacking specific clinical manifestations.CT and colonoscopy are helpful for the diagnosis of this disease,which need to be distinguished from colorectal cancer,Crohn's disease,and other pathological subtypes of lymphoma.The diagnosis still needs to be confirmed by pathological examination.This paper reports a case of intestinal mantle cell lymphoma complicated with ileocecal intussusception in an adult,aiming to improve the clinical and imaging doctors' understanding of this disease.


Subject(s)
Ileal Diseases , Intussusception , Lymphoma, Mantle-Cell , Humans , Lymphoma, Mantle-Cell/complications , Intussusception/etiology , Intussusception/diagnostic imaging , Intussusception/complications , Male , Ileal Diseases/etiology , Ileal Diseases/complications , Ileal Diseases/diagnostic imaging , Intestinal Neoplasms/complications , Intestinal Neoplasms/pathology , Intestinal Neoplasms/diagnostic imaging , Middle Aged , Ileocecal Valve/diagnostic imaging , Ileocecal Valve/pathology
4.
World J Gastroenterol ; 30(25): 3155-3165, 2024 Jul 07.
Article in English | MEDLINE | ID: mdl-39006389

ABSTRACT

BACKGROUND: Due to similar clinical manifestations and imaging signs, differential diagnosis of primary intestinal lymphoma (PIL) and Crohn's disease (CD) is a challenge in clinical practice. AIM: To investigate the ability of radiomics combined with machine learning methods to differentiate PIL from CD. METHODS: We collected contrast-enhanced computed tomography (CECT) and clinical data from 120 patients form center 1. A total of 944 features were extracted single-phase images of CECT scans. Using the last absolute shrinkage and selection operator model, the best predictive radiographic features and clinical indications were screened. Data from 54 patients were collected at center 2 as an external validation set to verify the robustness of the model. The area under the receiver operating characteristic curve, accuracy, sensitivity and specificity were used for evaluation. RESULTS: A total of five machine learning models were built to distinguish PIL from CD. Based on the results from the test group, most models performed well with a large area under the curve (AUC) (> 0.850) and high accuracy (> 0.900). The combined clinical and radiomics model (AUC = 1.000, accuracy = 1.000) was the best model among all models. CONCLUSION: Based on machine learning, a model combining clinical data with radiologic features was constructed that can effectively differentiate PIL from CD.


Subject(s)
Crohn Disease , Intestinal Neoplasms , Machine Learning , ROC Curve , Tomography, X-Ray Computed , Humans , Crohn Disease/diagnostic imaging , Female , Diagnosis, Differential , Male , Middle Aged , Adult , Intestinal Neoplasms/diagnostic imaging , Intestinal Neoplasms/pathology , Tomography, X-Ray Computed/methods , Retrospective Studies , Lymphoma/diagnostic imaging , Lymphoma/pathology , Aged , Sensitivity and Specificity , Contrast Media/administration & dosage , Young Adult , Radiomics
5.
Sci Rep ; 14(1): 15782, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982134

ABSTRACT

This study aims to assess the predictive capability of cylindrical Tumor Growth Rate (cTGR) in the prediction of early progression of well-differentiated gastro-entero-pancreatic tumours after Radio Ligand Therapy (RLT), compared to the conventional TGR. Fifty-eight patients were included and three CT scans per patient were collected at baseline, during RLT, and follow-up. RLT response, evaluated at follow-up according to RECIST 1.1, was calculated as a percentage variation of lesion diameters over time (continuous values) and as four different RECIST classes. TGR between baseline and interim CT was computed using both conventional (approximating lesion volume to a sphere) and cylindrical (called cTGR, approximating lesion volume to an elliptical cylinder) formulations. Receiver Operating Characteristic (ROC) curves were employed for Progressive Disease class prediction, revealing that cTGR outperformed conventional TGR (area under the ROC equal to 1.00 and 0.92, respectively). Multivariate analysis confirmed the superiority of cTGR in predicting continuous RLT response, with a higher coefficient for cTGR (1.56) compared to the conventional one (1.45). This study serves as a proof of concept, paving the way for future clinical trials to incorporate cTGR as a valuable tool for assessing RLT response.


Subject(s)
Disease Progression , Pancreatic Neoplasms , Stomach Neoplasms , Tomography, X-Ray Computed , Humans , Female , Male , Middle Aged , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/pathology , Aged , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/pathology , Tomography, X-Ray Computed/methods , Adult , ROC Curve , Neuroendocrine Tumors/diagnostic imaging , Neuroendocrine Tumors/pathology , Intestinal Neoplasms/diagnostic imaging , Intestinal Neoplasms/pathology , Proof of Concept Study , Tumor Burden
6.
Turk J Pediatr ; 66(3): 332-339, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-39024601

ABSTRACT

BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare in children and adolescents. Standard management of these tumors has not been well established due to their rarity in this age group. We aimed to report the clinical and pathological characteristics of patients with this rare disease followed and treated between the years 1993-2022. MATERIALS AND METHODS: The medical records of patients with GEP-NETs were reviewed. RESULTS: Fourteen patients (11 girls, 3 boys) were diagnosed with GEP-NET. The median age was 13 (9-18) years. Tumor localization was the appendix in 12, stomach in one and pancreas in one patient. Mesoappendix invasion was detected in four patients two of whom underwent right hemicolectomy (RHC) and lymph node dissection (LND). Of those, one patient had lymph node involvement. The other two had not further operations. Somatostatin was used in one with pancreatic metastatic disease and the other with gastric disease after surgery. No additional treatment was given in other patients. All patients are under follow-up without evidence of disease at a median follow-up of 85 months (7-226 months). CONCLUSION: GEP-NETs should be considered in the differential diagnosis of acute appendicitis and in cases with persistent abdominal pain. In children, there is invariably a favorable prognosis, and additional surgical interventions other than simple appendectomies generally do not provide benefits. Mesoappendix invasion may not necessitate RHC and LND.


Subject(s)
Intestinal Neoplasms , Neuroendocrine Tumors , Pancreatic Neoplasms , Stomach Neoplasms , Humans , Adolescent , Male , Female , Child , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/pathology , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/surgery , Neuroendocrine Tumors/pathology , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Stomach Neoplasms/diagnosis , Intestinal Neoplasms/surgery , Intestinal Neoplasms/diagnosis , Intestinal Neoplasms/pathology , Retrospective Studies
7.
Curr Biol ; 34(12): 2623-2632.e5, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38823383

ABSTRACT

The sense of taste is essential for survival, as it allows animals to distinguish between foods that are nutritious from those that are toxic. However, innate responses to different tastants can be modulated or even reversed under pathological conditions. Here, we examined whether and how the internal status of an animal impacts taste valence by using Drosophila models of hyperproliferation in the gut. In all three models where we expressed proliferation-inducing transgenes in intestinal stem cells (ISCs), hyperproliferation of ISCs caused a tumor-like phenotype in the gut. While tumor-bearing flies had no deficiency in overall food intake, strikingly, they exhibited an increased gustatory preference for aristolochic acid (ARI), which is a bitter and normally aversive plant-derived chemical. ARI had anti-tumor effects in all three of our gut hyperproliferation models. For other aversive chemicals we tested that are bitter but do not have anti-tumor effects, gut tumors did not affect avoidance behaviors. We demonstrated that bitter-sensing gustatory receptor neurons (GRNs) in tumor-bearing flies respond normally to ARI. Therefore, the internal pathology of gut hyperproliferation affects neural circuits that determine taste valence postsynaptic to GRNs rather than altering taste identity by GRNs. Overall, our data suggest that increased consumption of ARI may represent an attempt at self-medication. Finally, although ARI's potential use as a chemotherapeutic agent is limited by its known toxicity in the liver and kidney, our findings suggest that tumor-bearing flies might be a useful animal model to screen for novel anti-tumor drugs.


Subject(s)
Drosophila melanogaster , Taste , Animals , Taste/physiology , Drosophila melanogaster/physiology , Drosophila melanogaster/drug effects , Aristolochic Acids , Intestinal Neoplasms/drug therapy , Intestinal Neoplasms/pathology
9.
World J Surg Oncol ; 22(1): 151, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849854

ABSTRACT

BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare gastrointestinal malignancy forwhich survival is hampered by late diagnosis, complex responses to treatment, and poor prognosis. Accurate prognostic tools are crucial for optimizing treatment strategies and improving patient outcomes. This study aimed to develop and validate a nomogram based on the Surveillance, Epidemiology, and End Results (SEER) database to predict cancer-specific survival (CSS) in patients with SBA and compare it to traditional American Joint Committee on Cancer (AJCC) staging. METHODS: We analyzed data from 2,064 patients diagnosed with SBA between 2010 and 2020 from the SEER database. Patients were randomly assigned to training and validation cohorts (7:3 ratio). Kaplan‒Meier survival analysis, Cox multivariate regression, and nomograms were constructed for analysis of 3-year and 5-year CSS. The performance of the nomograms was evaluated using Harrell's concordance index (C-index), the area under the receiver operating characteristic (ROC) curve, calibration curves, decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: Multivariate Cox regression identified sex, age at diagnosis, marital status, tumor site, pathological grade, T stage, N stage, M stage, surgery, retrieval of regional lymph nodes (RORLN), and chemotherapy as independent covariates associated with CSS. In both the training and validation cohorts, the developed nomograms demonstrated superior performance to that of the AJCC staging system, with C-indices of 0.764 and 0.759, respectively. The area under the curve (AUC) values obtained by ROC analysis for 3-year and 5-year CSS prediction significantly surpassed those of the AJCC model. The nomograms were validated using calibration and decision curves, confirming their clinical utility and superior predictive accuracy. The NRI and IDI indicated the enhanced predictive capability of the nomogram model. CONCLUSION: The SEER-based nomogram offers a significantly superior ability to predict CSS in SBA patients, supporting its potential application in clinical decision-making and personalized approaches to managing SBA to improve survival outcomes.


Subject(s)
Adenocarcinoma , Intestinal Neoplasms , Nomograms , SEER Program , Humans , Male , Female , SEER Program/statistics & numerical data , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Middle Aged , Survival Rate , Aged , Intestinal Neoplasms/mortality , Intestinal Neoplasms/pathology , Intestinal Neoplasms/therapy , Intestinal Neoplasms/diagnosis , Prognosis , Follow-Up Studies , Neoplasm Staging , Intestine, Small/pathology , ROC Curve , Adult , Retrospective Studies
10.
Medicine (Baltimore) ; 103(23): e38465, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847694

ABSTRACT

RATIONALE: Intestinal T-cell lymphomas are exceedingly rare diseases. Intestinal T-cell lymphoma NOS, as a "wastebasket" category, is difficult to diagnosis. Endoscopy can identify abnormal mucosa in most patients at a reasonably early stage. Therefore, it is crucial to increase the understanding of endoscopists in terms of the endoscopic characteristics of ITCL. PATIENT CONCERNS: A 74-year-old male alone with wasting as the major complaint, had multiple polypoid lesions in the large intestine. The patient then had endoscopic care. DIAGNOSES: Only 1 polypoid lesion on white-light endoscopy in the sigmoid colon was pathologically diagnosed as intestinal T-cell lymphomas, not otherwise specified (ITCL-NOS). INTERVENTIONS: The patient underwent intensity-reduced CHOP therapy. OUTCOMES: The patient is still with controlled disease but developed chemotherapy-related side effects. LESSONS: In the individual with unexplained anemia and waste, endoscopy should not be delayed. For each of polypoid lesion on white-light endoscopy, the endoscopist need to remain cautious, because every lesion in the same patient can exhibit the independence of histopathological features. Meanwhile, we suggest that endoscopists should routinely observe the terminal ileum, even take biopsy samples if necessary.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Humans , Aged , Male , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, T-Cell/diagnosis , Lymphoma, T-Cell/pathology , Doxorubicin/therapeutic use , Vincristine/therapeutic use , Intestinal Neoplasms/diagnosis , Intestinal Neoplasms/pathology , Cyclophosphamide/therapeutic use , Prednisone/therapeutic use , Colonoscopy
11.
Lancet ; 403(10446): 2807-2817, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38851203

ABSTRACT

BACKGROUND: There are currently no standard first-line treatment options for patients with higher grade 2-3, well-differentiated, advanced, gastroenteropancreatic neuroendocrine tumours. We aimed to investigate the efficacy and safety of first-line [177Lu]Lu-DOTA-TATE (177Lu-Dotatate) treatment. METHODS: NETTER-2 was an open-label, randomised, parallel-group, superiority, phase 3 trial. We enrolled patients (aged ≥15 years) with newly diagnosed higher grade 2 (Ki67 ≥10% and ≤20%) and grade 3 (Ki67 >20% and ≤55%), somatostatin receptor-positive (in all target lesions), advanced gastroenteropancreatic neuroendocrine tumours from 45 centres across nine countries in North America, Europe, and Asia. We used interactive response technologies to randomly assign (2:1) patients to receive four cycles (cycle interval was 8 weeks ± 1 week) of intravenous 177Lu-Dotatate plus intramuscular octreotide 30 mg long-acting repeatable (LAR) then octreotide 30 mg LAR every 4 weeks (177Lu-Dotatate group) or high-dose octreotide 60 mg LAR every 4 weeks (control group), stratified by neuroendocrine tumour grade (2 vs 3) and origin (pancreas vs other). Tumour assessments were done at baseline, week 16, and week 24, and then every 12 weeks until disease progression or death. The primary endpoint was progression-free survival by blinded, independent, central radiology assessment. We did the primary analysis at 101 progression-free survival events as the final progression-free survival analysis. NETTER-2 is registered with ClinicalTrials.gov, NCT03972488, and is active and not recruiting. FINDINGS: Between Jan 22, 2020, and Oct 13, 2022, we screened 261 patients, 35 (13%) of whom were excluded. We randomly assigned 226 (87%) patients (121 [54%] male and 105 [46%] female) to the 177Lu-Dotatate group (n=151 [67%]) and control group (n=75 [33%]). Median progression-free survival was 8·5 months (95% CI 7·7-13·8) in the control group and 22·8 months (19·4-not estimated) in the 177Lu-Dotatate group (stratified hazard ratio 0·276 [0·182-0·418]; p<0·0001). During the treatment period, adverse events (of any grade) occurred in 136 (93%) of 147 treated patients in the 177Lu-Dotatate group and 69 (95%) of 73 treated patients in the control group. There were no study drug-related deaths during the treatment period. INTERPRETATION: First-line 177Lu-Dotatate plus octreotide LAR significantly extended median progression-free survival (by 14 months) in patients with grade 2 or 3 advanced gastroenteropancreatic neuroendocrine tumours. 177Lu-Dotatate should be considered a new standard of care in first-line therapy in this population. FUNDING: Advanced Accelerator Applications, a Novartis Company.


Subject(s)
Intestinal Neoplasms , Neuroendocrine Tumors , Octreotide , Organometallic Compounds , Pancreatic Neoplasms , Stomach Neoplasms , Humans , Octreotide/therapeutic use , Octreotide/administration & dosage , Octreotide/analogs & derivatives , Octreotide/adverse effects , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/mortality , Male , Neuroendocrine Tumors/drug therapy , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/radiotherapy , Neuroendocrine Tumors/mortality , Female , Middle Aged , Organometallic Compounds/therapeutic use , Organometallic Compounds/administration & dosage , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Stomach Neoplasms/mortality , Aged , Intestinal Neoplasms/drug therapy , Intestinal Neoplasms/pathology , Intestinal Neoplasms/radiotherapy , Intestinal Neoplasms/mortality , Adult , Radiopharmaceuticals/therapeutic use , Treatment Outcome , Neoplasm Grading , Progression-Free Survival
14.
Surg Endosc ; 38(7): 3905-3916, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38831215

ABSTRACT

BACKGROUND: Small intestinal stromal tumors (SISTs) are a rare type of mesenchymal tumor. Gender is known to influence the incidence and prognosis of various tumors, but its role on the survival of SISTs at the population level remains unclear. Therefore, we aim to explore the relationship between gender and the prognosis of SISTs using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Data on SISTs patients from 2000 to 2019 were derived from the SEER database. Multiple imputation was used to address missing data. Kaplan-Meier analyses and Cox proportional hazard models were applied to evaluate the impact of demographic and clinical characteristics on overall survival (OS) and cancer-specific survival (CSS). RESULTS: A total of 3513 patients with SISTs were analyzed, including 1921 males and 1592 females. Kaplan-Meier analysis coupled with log-rank testing demonstrated a significantly higher mortality rate among male patients compared to females (P < 0.001). Notably, female patients exhibited superior OS (hazard ratio [HR] 0.808, 95% confidence interval [CI] 0.724-0.902, P < 0.001) and CSS (HR 0.801, 95% CI 0.692-0.927, P = 0.003) compared to male patients. While the mean 1-year CSS rates were comparable between genders (95.3% for males vs. 96.0% for females, P = 0.332), male patients consistently showed lower mean survival rates at 3-, 5-, and 10-year intervals. Surgical intervention significantly boosted 5-year OS and CSS rates in both male and female patients (P < 0.001). Multivariate Cox regression analysis identified age, sex, grade, TNM stage, surgery, and mitotic rate as independent risk factors for OS and CSS in patients with SISTs. CONCLUSIONS: Our findings suggest that male patients with SISTs have a higher risk of mortality compared to female patients, indicating that gender may serve as a predictive indicator for survival in this patient population.


Subject(s)
Gastrointestinal Stromal Tumors , SEER Program , Humans , Male , Female , Middle Aged , Gastrointestinal Stromal Tumors/mortality , Gastrointestinal Stromal Tumors/surgery , Gastrointestinal Stromal Tumors/pathology , Sex Factors , Aged , Survival Rate , Prognosis , Intestinal Neoplasms/mortality , Intestinal Neoplasms/pathology , Adult , Kaplan-Meier Estimate , Intestine, Small/pathology , United States/epidemiology , Proportional Hazards Models , Retrospective Studies
15.
Zhonghua Yi Xue Za Zhi ; 104(21): 2003-2006, 2024 Jun 04.
Article in Chinese | MEDLINE | ID: mdl-38825945

ABSTRACT

To investigate the clinical characteristics of metastatic tumors in small intestine. The clinical manifestations, imaging and endoscopic findings, treatment methods and follow-up of patients with small bowel metastatic tumors admitted to the First Affiliated Hospital of Zhengzhou University from January 1, 2018 to December 31, 2022 were retrospectively analyzed. A total of 10 patients were included, including 7 males and 3 females, aged 33-77 (56.4±12.6) years. The main clinical manifestations were intestinal obstruction (8 cases), such as abdominal pain, abdominal distension, nausea, vomiting, and reduced defecation. Some patients had intussusception (abdominal pain, vomiting, black stool and other symptoms, 1 case) or gastrointestinal bleeding (1 case) with early symptoms imperceptible. The primary tumors include gastric cancer (3 cases), malignant melanoma (2 cases), ovarian cancer (2 cases), colon cancer (1 case), rectal cancer (1 case), and lung cancer (1 case). Most of the primary tumors were poorly differentiated (6 cases) or moderately to poorly differentiated (2 cases). The median time from primary tumor surgery to detection of small bowel metastasis [M (Q1, Q3)] was 22 (18, 28) months.The metastatic lesions were single (6 cases) or multiple (4 cases), in both jejunum and ileum. Positron emission tomography-computed tomography (PET-CT, 3 cases) and endoscopy (2 cases) were helpful for detection of small intestinal metastases. The main treatment methods were surgical resection (9 cases), supplemented by radiotherapy, targeted drugs, immunotherapy, etc. Postoperative recurrence and metastasis occurred in some patients (5 cases). Most patients died within 4 to 29 months after diagnosis. Metastatic tumors in small intestine are rare in clinical practice with atypical early symptoms. The patients often present with complications such as intestinal obstruction, which is prone to delayed diagnosis and poor prognosis.


Subject(s)
Intestinal Neoplasms , Intestine, Small , Humans , Female , Middle Aged , Male , Aged , Intestine, Small/pathology , Adult , Retrospective Studies , Intestinal Neoplasms/pathology , Intestinal Obstruction/etiology , Melanoma/pathology , Stomach Neoplasms/pathology
16.
J Vet Intern Med ; 38(4): 2316-2323, 2024.
Article in English | MEDLINE | ID: mdl-38858174

ABSTRACT

BACKGROUND: Regional lymph nodes are frequently sampled in cats with suspected intestinal lymphoma; however, their diagnostic value has not been explored. OBJECTIVES: To investigate whether histologic and immunohistochemical analysis of mesenteric lymph nodes correlates with the diagnosis of intestinal lymphoma in cats. ANIMALS: One hundred 2 client-owned cats diagnosed with intestinal lymphoma. METHODS: Retrospective study. The inclusion criteria required a full-thickness biopsy of the small intestine and concurrent excision of mesenteric lymph nodes. Histologic and immunophenotypic analyses were performed on intestinal biopsies and corresponding lymph nodes. Selected nodal samples diagnosed with reactive lymph nodes underwent clonality testing. RESULTS: Transmural T-cell lymphomas, encompassing small and large cell types, were predominant (64 cases, 62.7%), with large B-cell lymphomas being more frequently transmural (68.8%) than mucosal (31.2%). Among all lymph nodes examined, 44 (43.1%; 95% CI: 33.9%-52.8%) exhibited neoplastic infiltration. Among cases of small cell lymphoma, 51 out of 72 (70.8%; 95% CI: 59.4%-80.1%) showed no nodal involvement. Clonality results correctly identified 19/30 (63.3%; 95% CI: 45.5%-78.2%) reactive lymph nodes. Concerns were raised regarding clonal identification in the remaining cases and potential misdiagnoses based on phenotypic characteristics. CONCLUSION AND CLINICAL IMPORTANCE: The study underscores the potential drawbacks of relying solely on mesenteric lymph nodes for diagnosing intestinal lymphomas in cats, particularly small cell subtypes. It emphasizes the importance of full-thickness biopsies for assessing transmural infiltration and recommends caution when utilizing mesenteric lymph nodes for histologic, immunohistochemical and clonality evaluations in mucosal lymphomas. Despite limitations, this research highlights the need for comprehensive diagnostic strategies in cats with intestinal lymphoma.


Subject(s)
Cat Diseases , Intestinal Neoplasms , Lymph Nodes , Lymphoma , Animals , Cats , Cat Diseases/pathology , Cat Diseases/diagnosis , Retrospective Studies , Intestinal Neoplasms/veterinary , Intestinal Neoplasms/pathology , Intestinal Neoplasms/diagnosis , Lymph Nodes/pathology , Male , Female , Lymphoma/veterinary , Lymphoma/pathology , Lymphoma/diagnosis , Biopsy/veterinary , Intestine, Small/pathology , Mesentery/pathology , Lymphoma, T-Cell/veterinary , Lymphoma, T-Cell/pathology , Lymphoma, T-Cell/diagnosis
17.
Mol Biol Rep ; 51(1): 704, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824233

ABSTRACT

BACKGROUND: Tumor modeling using organoids holds potential in studies of cancer development, enlightening both the intracellular and extracellular molecular mechanisms behind different cancer types, biobanking, and drug screening. Intestinal organoids can be generated in vitro using a unique type of adult stem cells which are found at the base of crypts and are characterized by their high Lgr5 expression levels. METHODS AND RESULTS: In this study, we successfully established intestinal cancer organoid models by using both the BALB/c derived and mouse embryonic stem cells (mESCs)-derived intestinal organoids. In both cases, carcinogenesis-like model was developed by using azoxymethane (AOM) treatment. Carcinogenesis-like model was verified by H&E staining, immunostaining, relative mRNA expression analysis, and LC/MS analysis. The morphologic analysis demonstrated that the number of generated organoids, the number of crypts, and the intensity of the organoids were significantly augmented in AOM-treated intestinal organoids compared to non-AOM-treated ones. Relative mRNA expression data revealed that there was a significant increase in both Wnt signaling pathway-related genes and pluripotency transcription factors in the AOM-induced intestinal organoids. CONCLUSION: We successfully developed simple carcinogenesis-like models using mESC-based and Lgr5 + stem cell-based intestinal organoids. Intestinal organoid based carcinogenesi models might be used for personalized cancer therapy in the future.


Subject(s)
Azoxymethane , Carcinogenesis , Mouse Embryonic Stem Cells , Organoids , Wnt Signaling Pathway , Animals , Organoids/metabolism , Organoids/pathology , Mice , Azoxymethane/toxicity , Carcinogenesis/pathology , Carcinogenesis/chemically induced , Carcinogenesis/genetics , Mouse Embryonic Stem Cells/metabolism , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/genetics , Mice, Inbred BALB C , Intestines/pathology , Intestinal Neoplasms/pathology , Intestinal Neoplasms/chemically induced , Intestinal Neoplasms/genetics , Intestinal Neoplasms/metabolism , Disease Models, Animal , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology
18.
J Vet Med Sci ; 86(7): 748-755, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38811188

ABSTRACT

Nuclear expression of ß-catenin has been reported in canine intestinal epithelial tumors (IETs) and colorectal inflammatory polyps (CIPs) with dysplastic epithelia. However, the role of the Wnt/ß-catenin signaling pathway in these lesions remains unclear. To investigate the association between the nuclear ß-catenin expression and the activation of the Wnt/ß-catenin signaling pathway, immunohistochemistry and mutation analyses were conducted on 64 IETs and 20 CIPs. IETs and CIPs with ß-catenin nuclear and/or cytoplasm immunolabeling were classified as ß-catenin (+). The immunostaining scores of c-Myc and Cyclin D1 and Ki-67 index were significantly higher in ß-catenin (+) cases than in ß-catenin (-) cases. Identical APC mutations (p.E154D and p.K155X) were detected in 6/41 ß-catenin (+) IETs; all 6 of IETs with APC mutations were Jack Russell Terriers. CTNNB1 mutations were detected in 29/42 ß-catenin (+) IETs, 3/11 ß-catenin (+) CIPs, and 2/22 ß-catenin (-) IETs, most of which were hotspots associated with human colorectal carcinoma. In one Miniature Dachshund diagnosed with a CIP that subsequently developed into an IET, the same CTNNB1 mutation was detected in both lesions. The immunohistochemical results suggest that cell proliferative activity in ß-catenin (+) cases may be associated with activation of the Wnt/ß-catenin signaling pathway. The mutation analysis results suggest that CTNNB1 mutations may be associated with cytoplasmic ß-catenin accumulation in IET and CIP. Furthermore, the dysplastic epithelium in CIP may progress to IET through the activation of the Wnt/ß-catenin signaling pathway by the CTNNB1 mutation.


Subject(s)
Dog Diseases , Mutation , Wnt Signaling Pathway , beta Catenin , Animals , Dogs , beta Catenin/genetics , beta Catenin/metabolism , Dog Diseases/genetics , Dog Diseases/pathology , Dog Diseases/metabolism , Wnt Signaling Pathway/genetics , Female , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Male , Immunohistochemistry/veterinary , Intestinal Neoplasms/veterinary , Intestinal Neoplasms/genetics , Intestinal Neoplasms/pathology , Intestinal Neoplasms/metabolism
19.
J Natl Compr Canc Netw ; 22(5)2024 May 14.
Article in English | MEDLINE | ID: mdl-38744314

ABSTRACT

BACKGROUND: High-grade neuroendocrine neoplasms (NENs) comprise both well-differentiated grade 3 neuroendocrine tumors (G3 NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) nearly always include poorly differentiated NEC as the neuroendocrine component. The efficacy and safety of frontline mFOLFIRINOX chemotherapy has never been investigated in patients with high-grade NENs. PATIENTS AND METHODS: We conducted a multi-institutional retrospective analysis of patients with advanced high-grade NEN of the gastroenteropancreatic tract or of unknown origin seen between February 2016 and April 2023 who received treatment with frontline mFOLFIRINOX. RESULTS: A total of 35 patients were included (G3 NETs: n=2; NECs: n=25; MiNENs: n=8; stage III: n=5; stage IV: n=30). The objective response rate was 77% (complete response: 3%; partial response: 74%). Median progression-free survival was 12 months (95% CI, 9.2-16.2 months) and median overall survival was 20.6 months (95% CI, 17.2-30.6 months). No significant differences in efficacy were seen according to primary site, histopathology, and Ki-67 proliferative index. All 5 patients with stage III disease who received mFOLFIRINOX obtained an objective response and underwent radical surgery or definitive radiotherapy with curative intent, with a recurrence rate of 40%. Grade 3 or 4 adverse events were observed in 43% of patients (mainly neutropenia and diarrhea). Females were at significantly increased risk of developing severe toxicities. CONCLUSIONS: mFOLFIRINOX shows antitumor activity against high-grade NENs. Well-designed, prospective clinical trials are needed to assess the efficacy of mFOLFIRINOX in both the neoadjuvant and metastatic settings.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Irinotecan , Neoplasm Grading , Neuroendocrine Tumors , Pancreatic Neoplasms , Humans , Female , Male , Middle Aged , Neuroendocrine Tumors/drug therapy , Neuroendocrine Tumors/pathology , Aged , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/mortality , Retrospective Studies , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Irinotecan/therapeutic use , Irinotecan/pharmacology , Intestinal Neoplasms/drug therapy , Intestinal Neoplasms/pathology , Intestinal Neoplasms/mortality , Oxaliplatin/therapeutic use , Oxaliplatin/pharmacology , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Fluorouracil/therapeutic use , Leucovorin/therapeutic use , Treatment Outcome
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