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.

[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.

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.

Defining the optimal segmentation method for measuring somatostatin receptor expressing tumor volume on 68 Ga-DOTATATE positron emission tomography/computed tomography to predict prognosis in patients with gastroenteropancreatic neuroendocrine tumors.

OBJECTIVE: We aimed to compare different segmentation methods used to calculate prognostically valuable volumetric parameters, somatostatin receptor expressing tumor volume (SRETV), and total lesion somatostatin receptor expression (TLSRE), measured by 68 Ga-DOTATATE PET/CT and to find the optimal segmentation method to predict prognosis. PATIENTS AND METHODS: Images of 34 patients diagnosed with gastroenteropancreatic neuroendocrine tumor (GEPNET) who underwent 68 Ga-DOTATATE PET/CT imaging were reanalyzed. Four different threshold-based methods (fixed relative threshold method, normal liver background threshold method, fixed absolute standardized uptake value (SUV) threshold method, and adaptive threshold method) were used to calculate SRETV and TLSRE values. SRETV of all lesions of a patient was summarized as whole body SRETV (WB-SRETV) and TLSRE of all lesions of a patient was computed as whole body TLSRE (WB-TLSRE). RESULTS: WB-SRETVs calculated with all segmentation methods were statistically significantly associated with progression-free survival except WB-SRETV at which was calculated using adaptive threshold method. The fixed relative threshold methods calculated by using 45% (WB-SRETV 45% ) and 60% (WB-SRETV 60% ) of the SUV value as threshold respectively, were found to have statistically significant highest prognostic value (C-index = 0.704, CI = 0.622-0.786, P  = 0.007). Among WB-TLSRE parameters, WB-TLSRE 35% , WB-TLSRE 40% , and WB-TLSRE 50% had the highest prognostic value (C-index = 0.689, CI = 0.604-0.774, P  = 0.008). CONCLUSION: The fixed relative threshold method was found to be the most effective and easily applicable method to measure SRETV on pretreatment 68 Ga-DOTATATE PET/CT to predict prognosis in GEPNET patients. WB-SRETV 45% (cutoff value of 11.8 cm 3 ) and WB-SRETV 60% (cutoff value of 6.3 cm 3 ) were found to be the strongest predictors of prognosis in GEPNET patients.

Discordance Rate and Risk Factor of Other Diagnostic Modalities for Small Bowel Tumors Detected by Device-Assisted Enteroscopy: A Korean Association for the Study of Intestinal Disease (KASID) Multicenter Study.

Background/Aims: Despite advances in imaging and endoscopic technology, diagnostic modalities for small bowel tumors are simultaneously performed. We investigated the discrepancy rate between each modality and predictive factors of discrepancy in patients with definite small bowel tumors. Methods: Data of patients with definite small bowel tumors who underwent both device-assisted enteroscopy (DAE) and computed tomography (CT) were retrieved from web-based enteroscopy registry database in Korea. Predictive risk factors associated with discrepancy were analyzed using logistic regression analysis. Results: Among 998 patients, 210 (21.0%) were diagnosed with small bowel tumor using DAE, in 193 patients with definite small bowel tumor, DAE and CT were performed. Of these patients, 12 (6.2%) showed discrepancy between examinations. Among 49 patients who underwent DAE and video capsule endoscopy (VCE) examination, 13 (26.5%) showed discrepancy between examinations. No significant independent risk factors were associated with concordance between DAE and CT in multivariate logistic regression analysis among the patients. In a multivariate logistic regression analysis, red blood cell transfusion was negatively associated with concordance between DAE and VCE in patients with small bowel tumor (odds ratio, 0.163; 95% confidence interval, 0.026 to 1.004; p=0.050). Conclusions: For small bowel tumors, the discrepancy rate between DAE and CT was 6.2%, and 26.5% between DAE and VCE. Despite developments in cross-sectional imaging (VCE and DAE modalities), discrepancies still exist. For small bowel bleeding that require significant transfusion while showing insignificant VCE findings, DAE should be considered as the next diagnostic approach, considering the possibility of missed small bowel tumor.

Absorbed Dose-Response Relationship in Patients with Gastroenteropancreatic Neuroendocrine Tumors Treated with [177Lu]Lu-DOTATATE: One Step Closer to Personalized Medicine.

[177Lu]Lu-DOTATATE has been approved for progressive and inoperable gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that overexpress somatostatin receptors. The absorbed doses by limiting organs and tumors can be quantified by serial postinfusion scintigraphy measurements of the γ-emissions from 177Lu. The objective of this work was to explore how postinfusion [177Lu]Lu-DOTATATE dosimetry could influence clinical management by predicting treatment efficacy (tumor shrinkage and survival) and toxicity. Methods: Patients with GEP-NETs treated with [177Lu]Lu-DOTATATE between 2016 and 2022 and who underwent dosimetry were included. Absorbed doses were calculated for healthy organs (liver, kidneys, bone marrow, and spleen) and tumors using PLANET Dose and the local energy deposition method based on serial posttreatment SPECT/CT. Up to 5 lesions per site were selected and measured on images collected at baseline and 3 mo after treatment end (measurement masked to the somatostatin receptor imaging uptake). For toxicity assessment, laboratory parameters were regularly monitored. Clinical data, including time to death or progression, were collected from the patients' health records. Correlations between absorbed doses by organs and toxicity and between absorbed doses by lesions and tumor volume variation were studied using regression models. Results: In total, 35 dosimetric studies were performed in patients with mostly grade 2 (77%) tumors and metastases in liver (89%), lymph nodes (77%), and bone (34%), and 146 lesions were analyzed: 1-9 lesions per patient, mostly liver metastases (65%) and lymph nodes (25%). The median total absorbed dose by tumors was 94.4 Gy. The absorbed doses by tumors significantly decreased between cycles. The absorbed dose by tumors was significantly associated with tumor volume variation (P < 0.001) 3 mo after treatment end, and it was a significant prognostic factor for survival. Toxicity analysis showed a correlation between the decrease of hematologic parameters such as lymphocytes or platelet concentrations and the absorbed doses by the spleen or bone marrow. The mean absorbed dose by the kidneys was not correlated with nephrotoxicity during the studied period. Conclusion: In patients treated with [177Lu]Lu-DOTATATE for GEP-NETs, tumor and healthy organ dosimetry can predict survival and toxicities, thus influencing clinical management.

Prevalence of metastases outside the liver and abdominal lymph nodes on 68Ga-DOTATOC-PET/CT in patients with small intestinal and pancreatic neuroendocrine tumours.

Metastases outside the liver and abdominal/retroperitoneal lymph nodes are nowadays detected frequently in patients with neuroendocrine tumours (NETs), owing to the high sensitivity of positron emission tomography (PET) with Gallium-68-DOTA-somatostatin analogues (68Ga-SSA) and concomitant diagnostic computed tomography (CT). Our aim was to determine the prevalence of extra-abdominal metastases on 68Ga-DOTATOC-PET/CT in a cohort of patients with small intestinal (Si-NET) and pancreatic NET (Pan-NET), as well as that of pancreatic metastasis in patients with Si-NET. Among 2090 patients examined by 68Ga-DOTATOC-PET/CT at two tertiary referral centres, a total of 1177 patients with a history of Si- or Pan-NET, were identified. The most recent 68Ga-DOTATOC-PET/CT report for each patient was reviewed, and the location and number of metastases of interest were recorded. Lesions outside the liver and abdominal nodes were found in 26% of patients (n = 310/1177), of whom 21.5% (255/1177) were diagnosed with Si-NET and 4.5% (55/1177) Pan-NET. Bone metastases were found in 18.4% (215/1177), metastases to Virchow's lymph node in 7.1% (83/1177), and lung/pleura in 4.8% (56/1177). In the subset of 255 Si-NET patients, 5.4% (41/255) manifested lesions in the pancreas, 1.5% in the breast (18/255), 1.3% in the heart (15/255) and 1% in the orbita (12/255). In Si-NET patients, the Ki-67 proliferation index was higher in those with ≥2 metastatic sites of interest, than with 1 metastatic site, (p <0.001). Overall, extra-abdominal or pancreatic metastases were more often found in patients with Si-NET (34%) than in those with Pan-NET (13%) (p <0.001). Bone metastases were 2.6 times more frequent in patients with Si-NET compared to Pan-NET patients (p <0.001). Lesions to the breast and orbita were encountered in almost only Si-NET patients. In conclusion, lesions outside the liver and abdominal nodes were detected in as many as 26% of the patients, with different prevalence and metastatic patterns in patients with Si-NET compared to Pan-NET. The impact of such metastases on overall survival and clinical decision-making needs further evaluation.

Radio-Guided Surgery with a New-Generation ß-Probe for Radiolabeled Somatostatin Analog, in Patients with Small Intestinal Neuroendocrine Tumors.

BACKGROUND: Radio-guided surgery (RGS) holds promise for improving surgical outcomes in neuroendocrine tumors (NETs). Previous studies showed low specificity (SP) using γ-probes to detect radiation emitted by radio-labeled somatostatin analogs. OBJECTIVE: We aimed to assess the sensitivity (SE) and SP of the intraoperative RGS approach using a ß-probe with a per-lesion analysis, while assessing safety and feasibility as secondary objectives. METHODS: This prospective, single-arm, single-center, phase II trial (NCT05448157) enrolled 20 patients diagnosed with small intestine NETs (SI-NETs) with positive lesions detected at 68Ga-DOTA-TOC positron emission tomography/computed tomography (PET/CT). Patients received an intravenous injection of 1.1 MBq/Kg of 68Ga-DOTA-TOC 10 min prior to surgery. In vivo measurements were conducted using a ß-probe. Receiver operating characteristic (ROC) analysis was performed, with the tumor-to-background ratio (TBR) as the independent variable and pathology result (cancer vs. non-cancer) as the dependent variable. The area under the curve (AUC), optimal TBR, and absorbed dose for the surgery staff were reported. RESULTS: The intraoperative RGS approach was feasible in all cases without adverse effects. Of 134 specimens, the AUC was 0.928, with a TBR cut-off of 1.35 yielding 89.3% SE and 86.4% SP. The median absorbed dose for the surgery staff was 30 µSv (range 12-41 µSv). CONCLUSION: This study reports optimal accuracy in detecting lesions of SI-NETs using the intraoperative RGS approach with a novel ß-probe. The method was found to be safe, feasible, and easily reproducible in daily clinical practice, with minimal radiation exposure for the staff. RGS might potentially improve radical resection rates in SI-NETs. CLINICAL TRIALS REGISTRATION: 68Ga-DOTATOC Radio-Guided Surgery with ß-Probe in GEP-NET (RGS GEP-NET) [NCT0544815; https://classic. CLINICALTRIALS: gov/ct2/show/NCT05448157 ].

Multimodality imaging features of small bowel cancers complicating Crohn's disease: a pictorial review.

Patients with Crohn's disease (CD) are at increased risk of developing small bowel cancer, since chronic inflammation may trigger the histopathological sequence that begins from low-grade dysplasia of the intestinal epithelium and may eventually lead to malignant transformation. Owing to their location in a portion of the gastrointestinal tract which is not easily accessible to conventional endoscopic techniques, the detection of CD-related small bowel cancers is still a clinical challenge. The radiological features of CD-related small bowel adenocarcinoma (SBA) in patients with CD have been described in some previous studies, including its appearance in both CT and MRI examinations. Radiological signs of active or fibrostenotic CD may be intermixed with those suggesting the presence of CD-related SBA. In CT studies, the most relevant findings consistent with malignant transformation are the presence of a stricture with irregular asymmetric thickening of small bowel walls, loss of mural stratification, and moderate enhancement after intravenous administration of iodinated contrast media, in association with enlarged adjacent mesenteric lymph nodes. Many of the CD-related SBA features that can be observed on CT imaging are similar to those detectable by MRI. This latter modality provides the additional value of the functional characterization of small bowel strictures, thereby helping to distinguish between inflammatory, fibrotic, and malignant stenosis in the setting of active CD. Positron Emission Tomography (PET)/CT enables the metabolic assessment of enlarged mesenteric lymph nodes, and PET/MRI fusion imaging can incorporate morphological, functional and metabolic information into a single set of imaging data, thus overcoming the limitations of the separate assessment of each individual modality. Owing to the low incidence and prevalence of this long-term complication of CD, we believe that a detailed multimodality pictorial essay on this topic, also including the PET-CT and fusion imaging documentation of some cases, would be useful to the medical literature.

Liver Imaging in Gastroenteropancreatic Neuroendocrine Neoplasms.

ABSTRACT: The incidence of neuroendocrine neoplasms (NENs) has gradually increased over the past few decades with the majority of patients presenting with metastases on initial presentation. The liver is the most common site of initial metastatic disease, and the presence of liver metastasis is an independent prognostic factor associated with a negative outcome. Because NENs are heterogenous neoplasms with variable differentiation, grading, and risk of grade transformation over time, accurate diagnosis and management of neuroendocrine liver lesions are both important and challenging. This is particularly so with the multiple liver-directed treatment options available. In this review article, we discuss the diagnosis, treatment, and response evaluation of NEN liver metastases.

Small Bowel Neuroendocrine Neoplasms-A Review.

ABSTRACT: Neuroendocrine neoplasms (NENs) are rapidly evolving small bowel tumors, and the patients are asymptomatic at the initial stages. Metastases are commonly observed at the time of presentation and diagnosis. This review addresses the small bowel NEN (SB-NEN) and its molecular, histological, and imaging features, which aid diagnosis and therapy guidance. Somatic cell number alterations and epigenetic mutations are studied to be responsible for sporadic and familial SB-NEN. The review also describes the grading of SB-NEN in addition to rare histological findings such as mixed neuroendocrine-non-NENs. Anatomic and nuclear imaging with conventional computed tomography, magnetic resonance imaging, computed tomographic enterography, and positron emission tomography are adopted in clinical practice for diagnosing, staging, and follow-up of NEN. Along with the characteristic imaging features of SB-NEN, the therapeutic aspects of imaging, such as peptide receptor radionuclide therapy, are discussed in this review.

Capsule endoscopy diagnosis of gastrointestinal melanoma.

Melanoma is a cancer that frequently metastasises to the small bowel, but most cases are asymptomatic and are diagnosed postmortem. Therefore, CT and PET CT cannot detect all lesions and conventional endoscopic study only detects 10-20% of lesions. In this study, we present the case of a 68-year-old patient with a history of cutaneous melanoma and a diagnosis of intestinal melanoma. Thanks to capsule endoscopy, two lesions compatible with cutaneous melanoma metastasis to the small bowel were detected, allowing a much more effective surgical planning. Capsule endoscopy is an innovative technique that improves preoperative diagnosis, as it is able to detect bowel segments that cannot be inspected by conventional endoscopy. It also has a better resolution than conventional CT, improving sensitivity in the detection of lesions.

Updates in the diagnosis and management of small-bowel tumors.

Small-bowel tumors represent a rare entity comprising 0.6% of all new cancer cases in the US, and only 3% of all gastrointestinal neoplasms. They are a heterogenous group of neoplasms comprising of about forty different histological subtypes with the most common being adenocarcinoma, neuroendocrine tumors, stromal tumors and lymphomas. Their incidence has been reportedly increasing over recent years, partly owing to the advances and developments in the diagnostic modalities. Small-bowel capsule endoscopy, device assisted enteroscopy and dedicated small-bowel cross-sectional imaging are complimentary tools, supplementing each other in the diagnostic process. Therapeutic management of small-bowel tumors largely depends on the histological type and staging at diagnosis. The aim of the present review article is to discuss relevant advances in the diagnosis and management of small-bowel tumors.

Symptoms Contributing to the Diagnosis of Small Bowel Tumors.

INTRODUCTION: Small bowel tumors (SBTs) are difficult to diagnose because of limited opportunities and technical difficulties in evaluating the small bowel. Asymptomatic conditions or nonspecific symptoms make SBT diagnosis more challenging. In Asia, SBTs are reported to be more frequently malignant lymphoma (ML), adenocarcinoma, and gastrointestinal stromal tumor (GIST). In this study, we examined 66 patients diagnosed with SBTs and determined their clinical characteristics. METHODS: This retrospective study was conducted from January 2013 to July 2020 at Kurume University Hospital. The modalities used to detect SBTs were computed tomography (CT), positron emission tomography, magnetic resonance imaging, and ultrasonography. Endoscopy was also performed in some cases to confirm SBT diagnosis. The study included 66 patients. The medical data collected included presenting symptoms, tumor location, underlying condition, diagnostic modalities, pathologic diagnosis, and treatment. RESULTS: ML and adenocarcinoma were the most common tumors (22.7%), followed by GIST (21.2%) and metastatic SBT (18.2%). Symptoms that led to SBT detection were abdominal pain (44.5%), asymptomatic conditions (28.8%), hematochezia (12.1%), and anemia (10.6%). CT was the most used modality to detect SBTs. Nineteen patients were asymptomatic, and SBTs were incidentally detected in them. GISTs and benign tumors were more often asymptomatic than other malignant tumors. CONCLUSION: Abdominal pain was the main symptom for SBTs in particular adenocarcinoma, ML, and metastatic SBT. In addition, GIST, which was highly prevalent in Asia, had fewer symptoms. An understanding of these characteristics may be helpful in the clinical practice of SBTs.

Lower gastrointestinal bleeding as an uncommon form of presentation in a small intestine neuroendocrine tumor.

Neuroendocrine tumors (NETs) are rare, with an annual incidence of 10/100,000 inhabitants, with an increase in incidence in the last 30 years that probably is due to an improvement in diagnostic techniques. However, NETs the second neoplasia most prevalent advanced disease of the gastrointestinal tract due to its high survival. It´s way of presentation is usually with vague symptoms and often without an incidental diagnosis from the use of imaging techniques. A correct differential diagnosis will allow us its early diagnosis and its treatment. We present the case of a patient diagnosed with NET whose symptoms of presentation was lower gastrointestinal bleeding with a negative endoscopic study.

Fully-automated detection of small bowel carcinoid tumors in CT scans using deep learning.

BACKGROUND: Small bowel carcinoid tumor is a rare neoplasm and increasing in incidence. Patients with small bowel carcinoid tumors often experience long delays in diagnosis due to the vague symptoms, slow growth of tumors, and lack of clinician awareness. Computed tomography (CT) is the most common imaging study for diagnosis of small bowel carcinoid tumor. It is often used with positron emission tomography (PET) to capture anatomical and functional aspects of carcinoid tumors and thus to increase the sensitivity. PURPOSE: We compared three different kinds of methods for the automatic detection of small bowel carcinoid tumors on CT scans, which is the first to the best of our knowledge. METHODS: Thirty-three preoperative CT scans of 33 unique patients with surgically-proven carcinoid tumors within the small bowel were collected. Ground-truth segmentation of tumors was drawn on CT scans by referring to available 18 F-DOPA PET scans and the corresponding radiology report. These scans were split into the trainval set (n = 24) and the test positive set (n= 9). Additionally, 22 CT scans of 22 unique patients who had no evidence of the tumor were collected to comprise the test negative set. We compared three different kinds of detection methods, which are detection network, patch-based classification, and segmentation-based methods. We also investigated the usefulness of small bowel segmentation for reduction of false positives (FPs) for each method. Free-response receiver operating characteristic (FROC) curves and receiver operating characteristic (ROC) curves were used for lesion- and patient-level evaluations, respectively. Statistical analyses comparing the FROC and ROC curves were also performed. RESULTS: The detection network method performed the best among the compared methods. For lesion-level detection, the detection network method, without the small bowel segmentation-based filtering, achieved sensitivity values of (60.8%, 81.1%, 82.4%, 86.5%) at per-scan FP rates of (1, 2, 4 ,8), respectively. The use of the small bowel segmentation did not improve the performance ( p = 0.742 $p=0.742$ ). For patient-level detection, again the detection network method, but with the small bowel segmentation-based filtering, achieved the highest AUC of 0.86 with a sensitivity of 78% and specificity of 82% at the Youden point. CONCLUSIONS: The carcinoid tumors in this patient population were very small and potentially difficult to diagnose. The presented method showed reasonable sensitivity at small numbers of FPs for lesion-level detection. It also achieved a promising AUC for patient-level detection. The method may have clinical application in patients with this rare and difficult to detect disease.

Imaging of Small-Bowel Neuroendocrine Neoplasms: AJR Expert Panel Narrative Review.

Neuroendocrine neoplasms (NENs) of the small bowel are typically slow-growing lesions that remain asymptomatic until reaching an advanced stage. Imaging modalities for lesion detection, staging, and follow-up in patients with known or suspected NEN include CT enterography, MR enterography, and PET/CT using a somatostatin receptor analog. FDG PET/CT may have a role in the evaluation of poorly differentiated NENs. Liver MRI, ideally with a hepatocyte-specific contrast agent, should be used in the evaluation of hepatic metastases. Imaging informs decisions regarding both surgical approaches and systematic therapy (specifically, peptide receptor radionuclide therapy). This AJR Expert Panel Narrative Review describes the multimodality imaging features of small-bowel NENs; explores the optimal imaging modalities for their diagnosis, staging, and follow-up; and discusses how imaging may be used to guide therapy.