[Intestinal Mantle Cell Lymphoma Complicated With Ileocecal Intussusception in Adults:Report of One Case].

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.

Evaluation of a blood miRNA/mRNA signature to follow-up Lu-PRRT therapy for G1/G2 intestinal neuroendocrine tumors.

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.

Computed tomography-based radiomics combined with machine learning allows differentiation between primary intestinal lymphoma and Crohn's disease.

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.

[Histo- and molecular pathology in gastroenteropancreatic neuroendocrine neoplasms]. / Histo- und Molekularpathologie bei gastroenteropankreatischen neuroendokrinen Neoplasien.

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.

Cylindrical TGR as early radiological predictor of RLT progression in GEPNETs: a proof of concept.

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.

Gastroenteropancreatic neuroendocrine tumors in children and adolescents.

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.

Intestinal Clear Cell Sarcoma-A Case Presentation of an Extremely Rare Tumor and Literature Review.

Background: Clear cell sarcoma (CCS) is an extremely rare form of sarcoma representing less than 1% of all soft-tissue sarcomas. It has morphological, structural, and immunohistochemical similarities to malignant melanoma, affecting young adults and equally affecting both sexes, and is usually located in the tendinous sheaths and aponeuroses of the limbs. Gastrointestinal localization is exceptional, with less than 100 cases reported thus far. The gene fusion of activating transcription factor 1 (ATF1) and the Ewing sarcoma breakpoint region 1 (EWSR1) are pathognomonic for clear cell sarcoma, representing the key to the diagnosis. CCS is an extremely aggressive tumor, with >30% having distant or lymphatic metastasis at the time of diagnostic, and it has a high recurrence rate of over 80% in the first year after diagnosis and a high tendency for metastatic dissemination. Given the rarity of this tumor, there is no standardized treatment. Early diagnosis and radical surgery are essential in the treatment of CCS both for the primary tumor and for recurrence or metastasis. Chemo-radiotherapy has very little effect and is rarely indicated, and the role of targeted therapies is still under investigation. Case presentation: We present an extremely rare case of intestinal CSS in a 44-year-old Caucasian female. The patient, asymptomatic, first presented for a routine checkup and was diagnosed with mild iron-deficiency anemia. Given her family history of multiple digestive cancers, additional investigations were requested (gastroscopy, colonoscopy, tumoral markers and imaging) and the results were all within normal limits. In the subsequent period, the patient experienced mild diffuse recurrent abdominal pain, which occurred every 2-3 months. Two years later, the patient presented with symptoms of intestinal obstruction and underwent an emergency laparotomy followed by segmental enterectomy and regional lymphadenectomy for stenotic tumor of the jejunum. Histology, immunohistochemistry, and genetic testing established the diagnosis of CCS. No adjuvant therapy was indicated. Initially, no signs of recurrence or metastasis were detected, but after 30 and 46 months, respectively, from the primary treatment, the patient developed liver metastasis and pericolic peritoneal implants treated by atypical hepatic resections and right hemicolectomy. The patient remains under observation.

The impact of gender on survival outcomes in patients with small intestinal stromal tumors: a comprehensive analysis using the SEER database.

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.

[177Lu]Lu-DOTA-TATE plus long-acting octreotide versus high­dose long-acting octreotide for the treatment of newly diagnosed, advanced grade 2-3, well-differentiated, gastroenteropancreatic neuroendocrine tumours (NETTER-2): an open-label, randomised, phase 3 study.

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.

[The clinical characteristics of metastatic tumors in small intestine].

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.

[The Research Progress in the Diagnosis and Treatment of Primary Intestinal Diffuse Large B-cell Lymphoma--Review].

Primary intestinal diffuse large B-cell lymphoma (PI-DLBCL) is clinically rare, but in recent years, with the gradual maturity of pathology and molecular biology technology, its incidence rate and diagnosis rate have also increased. Due to the lack of specificity of the clinical symptoms of PI-DLBCL, it is easy to misdiagnose and miss the diagnosis, and there is no consensus on the best treatment of PI-DLBCL in clinical practice. Therefore, by retrieving the latest literature at home and abroad, this review systematically discusses the pathogenesis, clinical manifestations, diagnostic criteria, treatment and prognosis of PI-DLBCL, in order to improve the understanding of rare PI-DLBCL in hematology and oncology, and provide reference for basic research and clinical diagnosis and treatment of PI-DLBCL.

Gastroenteropancreatic neuroendocrine neoplasms: current development, challenges, and clinical perspectives.

Neuroendocrine neoplasms (NENs) are highly heterogeneous and potentially malignant tumors arising from secretory cells of the neuroendocrine system. Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are the most common subtype of NENs. Historically, GEP-NENs have been regarded as infrequent and slow-growing malignancies; however, recent data have demonstrated that the worldwide prevalence and incidence of GEP-NENs have increased exponentially over the last three decades. In addition, an increasing number of studies have proven that GEP-NENs result in a limited life expectancy. These findings suggested that the natural biology of GEP-NENs is more aggressive than commonly assumed. Therefore, there is an urgent need for advanced researches focusing on the diagnosis and management of patients with GEP-NENs. In this review, we have summarized the limitations and recent advancements in our comprehension of the epidemiology, clinical presentations, pathology, molecular biology, diagnosis, and treatment of GEP-NETs to identify factors contributing to delays in diagnosis and timely treatment of these patients.

Development and validation of a nomogram for predicting cancer-specific survival in small-bowel adenocarcinoma patients using the SEER database.

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.

Intestinal T-cell lymphomas NOS presenting as a polypoidal lesion: A case report.

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.

The diagnostic relevance of mesenteric lymph node biopsy in small intestinal lymphoma in cats.

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.