Small Bowel Tumors Research Articles

SMALL BOWEL LEIOMYOSARCOMA:A RARE CASE REPORT

leiomyosarcoma is a rare type of malignant tumor that arises from smooth muscle cells.it is classfied as a soft tissue sarcoma.tumors of small bowel amount for less than 5 % of all gastrointestinal malignancies with sarcomas ranking 5 th (~1.2%). small bowel tumors are usually asymptomatic at the early stages & difficult to visualise by upper & lower endoscopy LMS belongs to a heterogeneous group of soft tissue neoplasms, and with its aggressive nature, it often presents local recurrence and visceral metastases. As in the presented case, clinical manifestation of this disease, as in other small bowel tumours, is unspecific.here we discuss a rare case presentation of the same

Survival in Colon, Rectal and Small Intestinal Cancers in the Nordic Countries through a Half Century.

Background: Survival studies in intestinal cancers have generally shown favorable development, but few studies have been able to pinpoint the timing of the changes in survival over an extended period. Here, we compared the relative survival rates for colon, rectal and small intestinal cancers from Denmark (DK), Finland (FI), Norway (NO) and Sweden (SE). Design: Relative 1-, 5- and 5/1-year conditional survival data were obtained from the NORDCAN database for the years 1971-2020. Results: The 50-year survival patterns were country-specific. For colon and rectal cancers, the slopes of survival curves bended upwards for DK, were almost linear for NO and bended downwards for FI and SE; 5-year survival was the highest in DK. Survival in small intestinal cancer was initially below colon and rectal cancers but in FI and NO it caught up toward the end of the follow-up. Conclusions: Relative survival in intestinal cancers has developed well in the Nordic countries, and DK is an example of a country which in 20 years was able to achieve excellent survival rates in colon and rectal cancers. In the other countries, the increase in survival curves for colon and rectal cancer has slowed down, which may be a challenge posed by metastatic cancers.

The Wnt signaling pathway in gastrointestinal cancers.

807 Background: Activation of the Wnt signaling pathway leads to increases in β-catenin levels, which subsequently increases transcription of various genes, including those involved in cell proliferation. Dysregulation of the Wnt signaling pathway has been observed in numerous gastrointestinal (GI) cancers. Here we examine Wnt pathway activation across all GI cancers by investigating alterations in certain genes of the Wnt pathway, which may identify patients eligible for clinical trials. Methods: The Oncomap ExTra genomic profiling assay utilizes tumor-normal, whole-exome, whole-transcriptome DNA and RNA sequencing to identify somatic alterations in tumors. The assay detects single-nucleotide substitutions, indels, copy number alterations, alternative transcripts, and gene fusions. Alterations in genes that activate Wnt signaling and their frequency across all GI cancers was determined. Results: A total of 1928 patients assayed April 2018 to July 2022 were included. The Wnt signaling pathway was activated in 922 (47.8%) patients. Wnt pathway activation varied substantially across GI cancers, from 81.1% in colorectal cancer (CRC) to 3.4% in anal cancer. APC was the most commonly altered gene in CRC, small bowel and biliary carcinomas. CTNNB1 was predominant in liver (41.2%), MEN1 in neuroendocrine (14.6%), and RNF43 in gastric (9.4%) cancer. Of 921 patients with alterations in the Wnt pathway, 5.2% had a co-mutation in another Wnt pathway-related gene. RSPO2/3 fusions were found in 4 CRC, 1 stomach, 1 biliary, and 1 small bowel cancer and were mutually exclusive with other alterations in the Wnt pathway. Conclusions: Wnt signaling is activated in about half of all GI cancers, and APC alterations are the most frequently observed. Whole transcriptome profiling allowed us to identify RSPO2/3 fusions, which also contribute to activation of the Wnt pathway. Wnt activation appears to be a particularly important in CRC, with 81.1% of CRC having a Wnt pathway alteration. Our results highlight the therapeutic potential of targeting the abnormal Wnt/β-catenin signaling pathway in GI malignancies. [Table: see text]

Prevalence and genomic landscape of BRAF alterations across gastrointestinal cancers.

806 Background: BRAF V600E mutations can lead to activation of the MEK/ERK pathway. The combination of dabrafenib plus trametinib was recently FDA-approved for use in these BRAF V600E altered unresectable or metastatic cancers. BRAF non-V600 alterations also increase phosphorylation of MEK and ERK and are potential candidates for MEK/ERK inhibitors. Here we examine the frequency of BRAF mutations and their genomic background across GI cancers. Methods: The Oncomap ExTra genomic profiling assay utilizes tumor-normal, whole-exome, whole-transcriptome DNA and RNA sequencing to identify somatic alterations in tumors. The assay detects single-nucleotide substitutions, indels, copy number alterations, alternative transcripts, and gene fusions. Tumor mutational burden (TMB) and microsatellite instability (MSI) are also assessed. The frequency of BRAF and other gene alterations were identified across all GI cancers. Reported BRAF alterations were limited to those linked to an FDA approved therapy, clinical trial eligibility, and those deemed significant from review of the literature. Results: A total of 1927 patients with GI cancers were assayed between April 2018 to July 2022. The BRAF gene was mutated in 85 (4.4%) patients, which included 53 (2.8%) that were V600E and 32 (1.5%) that were non-V600, representing 37.6% of BRAF mutations. Colorectal and small bowel cancers had the highest frequencies of BRAF mutations at 7.6% and 7.1% respectively, and the frequency was lower in other GI cancers (0-2.3%). In addition to BRAF V600E, other mutations occurred across the kinase domain, including D594 (0.6%), K601E (0.3%), G466 (0.3%) and G469 (0.2%). BRAF fusions were found in 1 CRC and 2 pancreatic cancer cases. BRAF mutational status (altered versus not) was significantly associated with mutations in several other genes. In addition, BRAF status was significantly associated with TMB-high and MSI-high. Conclusions: Analysis of whole-exome and whole transcriptome sequencing data found actionable BRAF mutations in 4.4% of GI cancer patients, 37.6% of whom had BRAF mutations not at V600. Several biomarkers were significantly associated with BRAF alterations. Assays that are limited to DNA sequencing, or to targeted gene panels, may not detect mutations and fusions that could aid in therapy selection and prognosis. [Table: see text]

Stem cell retrograde: A new reason why colorectal cancer is more common than small intestinal cancer?

Stem cell retrograde: A new reason why colorectal cancer is more common than small intestinal cancer?

Social vulnerability and gastrointestinal cancer mortality among United States counties.

499 Background: The impact of socioeconomic status on gastrointestinal (GI) cancer mortality in the United States (US) is not well-established. We hypothesized that socially vulnerable populations have disproportionately higher mortality rates. Hence, we assessed the association of the social vulnerability index (SVI) with GI cancer mortality across US counties. Methods: Social vulnerability indices were obtained from the agency for toxic substances and disease registry (ATSDR) from 2014-2018 to compute percentile ranking scores (PRS: ranging from 0-1) for each US county. PRS were further categorized into quartiles (Q: 1st: 0-0.25 [least vulnerable]; 4th:0.75-1.00 [most vulnerable]). The wide-ranging online data for epidemiological research (WONDER) database was queried to abstract county-level age-adjusted mortality rates (AAMR) per 100,000 person-years (PY) for populations diagnosed with GI cancers. AAMRs were then linked with quartile rankings. Rate ratios (RR) of AAMRs between 4th and 1st Q were subsequently estimated with 95% confidence intervals using population-weighted, Poisson regression. Results: A total of 3142 counties were included in this analysis. The AAMR for overall deaths (OD) and premature deaths (PD; defined as death at age <65) in the GI cancer population was 53.8 and 17.7 per 100,000 PY. A gradient increase in GI cancer-related mortality was observed from 1st Q to 4th Q (OD: 49.2 vs 59.3; PD: 14.1 vs 21.3). This stepwise increase in AAMR over the quartiles was consistent across gender, different racial/ethnic subgroups, and rural/urban categories of counties. The AAMRs for OD were significantly higher in the 4th Q as compared to the 1st Q for gastric (RR: 1.67 [95% CI, 1.51-1.86]), hepatocellular including intrahepatic biliary (1.52 [1.45-1.61]), colorectal (1.21 [1.16-1.26]) and biliary (1.17 [1.06-1.28]) cancer. Similarly, significantly higher AAMRs for PD were observed in 4th Q vs1st Q for gastric (1.81 [1.60-2.05]), hepatocellular including intrahepatic biliary (1.78 [1.58-2.00]), biliary (1.64 [1.35-1.99]), colorectal (1.29 [1.21-1.39]) and pancreatic (1.16 [1.07-1.25]) cancer. However, no significant differences were observed for esophageal and small intestinal cancers. Men with gastric (1.58 [1.41-1.78]) and hepatocellular cancer (1.54 [1.43-1.66]), non-Hispanic Black population (1.54 [1.31-1.80]) with hepatocellular cancer, and Hispanic population with colorectal cancer (1.50 [1.31-1.72]) were observed to have higher overall mortality in the 4th Q compared to the 1st Q. The findings were similar for premature mortality. Conclusions: Population-level data suggests that the US counties with higher socio-economic adversities may be at an increased risk of GI cancer-related mortality. Investigations using patient-level data are required to probe the impact of socioeconomic vulnerabilities on cancer-related mortality.

Carcinoid Heart Disease in Patients Diagnosed with Small Bowel and Lung Neuroendocrine Tumors

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Imaging Recommendations for Diagnosis, Staging, and Management of Small Bowel and Colorectal Malignancies

AbstractSmall bowel malignancies are rare, though colorectal cancers are common. This article reviews the current imaging recommendations for small bowel and colorectal malignancies. Contrast-enhanced computed tomography (CT) is the imaging modality of choice for diagnosis/staging/response evaluation/follow-up of the small bowel and colonic tumors. Magnetic resonance imaging of the pelvis with high-resolution T2-weighted images in sagittal, oblique axial, and coronal planes is the imaging modality of choice for staging/response evaluation of anorectal tumors. CT colonography may be utilized as a tumor screening modality, alternative to colonoscopy.

Phase II evaluation of combination immunotherapy with CV301, N-803, bintrafusp alfa, and M9241 in patients with advanced small bowel and colorectal cancers.

116 Background: Although immune checkpoint inhibitors (CPI) are inactive as monotherapy for microsatellite stable (MSS) mCRC, preclinical modeling suggests that addition of other immune-oncology agents can produce antitumor activity. CV301 is a poxviral vaccine against CEA and MUC1. N-803 is an IL-15 superagonist. M9241 is tumor-targeted IL-12. Bintrafusp alfa (BA) is a bifunctional anti-PD-L1/TGF-βRII fusion protein. Methods: Patients with advanced MSS or proficient mismatch repair (pMMR) small bowel or CRC were eligible (NCT04491955). Patients enrolling to Arm 1 received triple therapy with BA 1200 mg IV every 2 weeks, N-803 15 mcg/kg SC every 4 weeks, and CV301 SC on D1, D15, D29, and monthly, thereafter. Patients enrolling to Arm 2 received quadruple therapy, with M9241 (8 mcg/kg or 16.8 mcg/kg SC every 4 weeks) plus BA (300 mg or 1200 mg IV), N-803 (10 mcg/kg SC) and CV301 SC, depending on dose escalation schedule. Results: Thirty patients (2 small intestinal, 17 colon, 11 rectal) were treated. All patients had received prior 5-fluorouracil-based treatment, with 29/30 (96.7%) having received ≥ 2 lines of systemic therapy. Twelve patients received triple therapy; 18 received quadruple therapy. Grade 3 treatment-related AEs (TRAEs) occurred in 8 patients (26.7%); anemia occurred most commonly (n = 5), with grade 3 gastrointestinal hemorrhages occurring in 2 patients (on quadruple therapy). Other grade 3 TRAEs included elevated cardiac troponin, AST, and alkaline phosphatase (n = 1 each; all with triple therapy), and adrenal insufficiency (n = 1; quadruple therapy). No grade 4 or 5 TRAEs occurred. Triple therapy resulted in disease reduction in 2 patients (7.5%, 25.6%); quadruple therapy resulted in disease reduction in 2 patients (26.7%, 70.6%). Median overall survival (OS) for triple and quadruple therapy have not been reached, with 12 month survival being 66.7% (95% CI: 33.7-86.0%) for triple therapy and 77.2% (95% CI: 43.3-92.3%) for quadruple therapy. Conclusions: Combination therapies with CV301, N-803, bintrafusp alfa, and M9241 had manageable safety profiles. Preliminary clinical activity was observed in patients with advanced MSS/pMMR small bowel or CRC. Median OS was promising as compared to historical median survivals of 6-7 months following receipt of multiple lines of therapy. Clinical trial information: NCT04491955 .

Effect of tumor location on the efficacy of chemotherapy for gastrointestinal stromal tumors.

790 Background: Gastrointestinal stromal tumors (GISTs) arise from multiple sites within the gastrointestinal tract. Since the introduction of imatinib in 2002, patients have seen improved overall survival. However, a recent National Cancer Database (NCDB) study suggested no survival benefit to adjuvant imatinib for colorectal GIST patients. Another recent study showed that small bowel GISTs have larger median tumor size and higher incidence of tumors with at least 5 mitoses compared to gastric GISTs. These findings suggest a differential tumor biology for GISTs arising from different primary tumor sites, potentially conferring differential response to imatinib. In this NCDB study, we compare overall survival outcomes with and without chemotherapy, stratifying by primary tumor site. Methods: We queried the NCDB from 2004-2018 for patients with GIST histology. We excluded patients with age <40, age>80, high comorbidity score, and patients who received additional therapy other than surgery or chemotherapy. Of the 22,846 patients meeting criteria for our study, 27 patients had tumors originating from the anus, 454 from the colon, 173 from the esophagus, 15,296 from the stomach, 556 from the rectum, 32 from the rectosigmoid junction, and 6,308 from the small intestine. 8,983 (39%) received chemotherapy. Treatment with chemotherapy was used to extrapolate response to imatinib, the mainstay of treatment. Results: Cox proportional hazards analysis demonstrated increased hazard of death for chemotherapy, increasing age, and comorbidity score of 1. Positive predictive factors for survival included female sex and later year of diagnosis. For anal, esophageal, gastric, and rectosigmoid GIST patients, there was no statistically significant overall survival benefit for any treatment modality. For colonic GISTs, neoadjuvant chemotherapy combined with surgery improved overall survival. For rectal GISTs, adjuvant chemotherapy with surgery also provided survival benefit. For small intestinal GISTs, surgery alone or surgery with neoadjuvant, adjuvant, or both neoadjuvant and adjuvant chemotherapy improved overall survival. Conclusions: While our study is retrospective and limited as a NCDB study, our Kaplan-Meier survival analysis demonstrated survival benefit for chemotherapy only in patients with colon, rectal, or small intestinal GIST tumors. Our Cox proportional analysis demonstrated an overall negative survival impact for chemotherapy. These findings lend further support to the idea that differential tumor biology at each primary site may lead to differential response to imatinib. Overall, our study provides rationale for further investigating the heterogeneity of GIST tumor microenvironments, as these differences could contribute to the differential treatment outcomes.

Risk of Cancer in Patients with Inflammatory Bowel Diseases and Keys for Patient Management.

Chronic inflammation in patients with Inflammatory Bowel Disease (IBD) leads to an increased risk of colorectal cancer, small bowel cancer, intestinal lymphoma and cholangiocarcinoma. However, treatments for IBD have also been associated with an increased risk of neoplasms. Patients receiving Thiopurines (TPs) have an increased risk of hematologic malignancies, non-melanoma skin cancer, urinary tract neoplasms and cervical cancer. Anti-TNFs have been associated with a higher risk of neoplasms, mainly lymphomas and melanomas; however, the data are controversial, and some recent studies do not confirm the association. Nevertheless, other biologic agents, such as ustekinumab and vedolizumab, have not shown an increased risk of any neoplasm to date. The risk of malignancies with tofacitinib exists, but its magnitude and relationship with previous treatment with TPs is not defined, so more studies from daily clinical practice are needed. Although biologic therapy seems to be safe for patients with current cancer or a prior history of cancer, as has been demonstrated in other chronic inflammatory conditions, prospective studies in this specific population are needed. Until that time, it is crucial to manage such conditions via the combined clinical expertise of the gastroenterologist and oncologist.

Endoscopic and histological characteristics of small bowel tumors diagnosed by double-balloon enteroscopy.

Double-balloon enteroscopy (DBE) allows for the diagnoses and treatment of small bowel tumors (SBTs). This study aimed to evaluate the utility of DBE for the diagnosis and treatment of SBTs. Patients diagnosed with SBTs who underwent DBE were included in this study. According to their endoscopic appearances, they were categorized as polyps or masses, and according to their histological characteristics, they were categorized as benign or malignant SBTs. A total of 704 patients were retrospectively analyzed, and 90 (12.8%) were diagnosed with SBTs. According to their endoscopic appearance, 48 (53.3%) had polyps and 42 (46.7%) had masses. Additionally, 53 (58.9%) and 37 (41.1%) patients had malignant and benign SBTs, respectively, depending on their histological characteristics. Patients diagnosed with polyps were younger than those diagnosed with masses (p<0.001). Patients diagnosed with benign SBTs were younger than those diagnosed with malignant SBT (p<0.001). Overall, histological diagnosis was determined using DBE in 73 (81.1%) patients. DBE is a useful method for diagnosing SBTs. Additionally, the histological type of the lesion can be determined using DBE.

The 10-month mortality rate among older patients treated for digestive system cancer during the first wave of the COVID-19 pandemic: The CADIGCOVAGE multicentre cohort study

IntroductionThe coronavirus disease 2019 (COVID-19) pandemic has had a dramatic impact on cancer diagnosis and care pathways. Here, we assessed the mid-term impact of the COVID-19 pandemic on older adults with cancer before, during and after the lockdown period in 2020. Materials and MethodsWe performed a retrospective, observational, multicentre cohort study of prospectively collected electronic health records. All adults aged 65 or over and having been newly treated for a digestive system cancer in our institution between January 2018 until August 2020 were enrolled. ResultsData on 7,881 patients were analyzed. Although the overall 10-month mortality rate was similar in 2020 vs. 2018–2019, the mortality rate among for patients newly treated in the 2020 post-lockdown period was (after four months of follow-up) significantly higher. A subgroup analysis revealed higher mortality rates for (i) patients diagnosed in the emergency department during the pre-lockdown period, (ii) patients with small intestine cancer newly treated during the post-lockdown period, and (iii) patients having undergone surgery with curative intent during the post-lockdown period. However, when considering individuals newly treated during the lockdown period, we observed lower mortality rates for (i) patients aged 80 and over, (ii) patients with a biliary or pancreatic cancer, and (iii) patients diagnosed in the emergency department. DiscussionThere was no overall increase in mortality among patients newly treated in 2020 vs. 2018–2019. Longer follow-up is needed to assess the consequences of the pandemic. A subgroup analysis revealed significant intergroup differences in mortality.

Endoscopic research methods for morphofunctional changes in the small intestine

Purpose: to analyze the results of diagnosis and treatment of tumors of the small intestine, which served as a source of small bowel bleeding. Materials and methods: 35 patients were analyzed: men - 19 (59.4%), women - 16 (41.6%) aged 19 to 85 years, with tumors and tumor-like lesions of the jejunum and ileum. The main indication for examination of the small intestine in these patients was the search for a source of bleeding that was not identified by standard diagnostic methods (esophagogastroduodenoscopy and colonoscopy). After analyzing the clinical picture in 5 examined patients with identified tumors of the small intestine, 3 (15.5%) clinical symptoms were manifested by obvious intestinal bleeding characterized by melena or hematochezia, and in 2 (10.5%) patients the course was latent. Conclusion: After analyzing the results of the diagnosis of small intestine tumors complicated by bleeding in young and middle-aged patients, the survey data demonstrate the importance of enteroscopy techniques in patients with iron deficiency anemia and chronic recurrent bleeding

Gastrointestinal malignancies in pregnancy.

Gastrointestinal malignancies, though uncommon in pregnancy, present several unique challenges with regards to diagnosis, staging, and treatment. Imaging the pregnant patient with a suspected or confirmed GI malignancy requires modifications to the radiologic modality of choice and protocol in order to minimize harm to the fetus, ensure accuracy in diagnosis and staging and guide treatment decisions. In this review article, we discuss theimaging approach to the pregnant patient with GI cancer, including safe radiologic modalities and modifications to imaging protocols. We also review the most common GI cancers encountered in pregnancy, including colorectal, pancreatic, gastric, and small bowel tumors, with emphasis to imaging findings, staging, and treatment considerations.

Mismatch Repair and Microsatellite Instability Testing for Immune Checkpoint Inhibitor Therapy: ASCO Endorsement of College of American Pathologists Guideline

The College of American Pathologists (CAP) has developed a guideline on testing for mismatch repair (MMR) and microsatellite instability (MSI) for patients considered for immune checkpoint inhibitor therapy. ASCO has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations. The CAP guideline was reviewed for developmental rigor by methodologists. An ASCO Endorsement Panel subsequently reviewed the content and the recommendations. The ASCO Endorsement Panel determined that the recommendations from the CAP guideline, published on August 3, 2022, are clear, thorough, and based on the most relevant scientific evidence. ASCO endorses Mismatch Repair and Microsatellite Instability Testing for Immune Checkpoint Inhibitor Therapy: Guideline From the College of American Pathologists in Collaboration With the Association for Molecular Pathology and Fight Colorectal Cancer. Within the guideline, MMR immunohistochemistry (IHC), MSI polymerase chain reaction, and MSI next-generation sequencing are all recommended testing options for colorectal cancer, MMR-IHC and MSI-polymerase chain reaction for gastroesophageal and small bowel cancer, and only MMR-IHC for endometrial cancer. No recommendation in favor of any testing method over another could be made for any other cancer. Tumor mutational burden was not recommended as a surrogate for DNA MMR deficiency. If MMR deficiency consistent with Lynch syndrome is detected, it should be communicated to the treating physician.Additional information is available at www.asco.org/molecular-testing-and-biomarkers-guidelines.

Computed tomographic findings may be useful for differentiating small intestinal adenocarcinomas, lymphomas, and spindle cell sarcomas in dogs.

An improved understanding of the CT characteristics for histologically confirmed primary intestinal tumors would be helpful for guiding prognosis and treatment plans in affected dogs. This retrospective, multi-center, analytical study aimed to evaluate the CT characteristics for the differentiation of adenocarcinoma, lymphoma, and spindle cell sarcoma (SCS) in dogs. Thirty-seven dogs who underwent contrast CT and histopathological examinations were included (adenocarcinomas, n=11; lymphomas, n=12; SCS, n=14). Quantitative and qualitative CT parameters, including tumor morphology, contrast enhancement pattern, Hounsfield unit (HU) value, and presence or absence of intraabdominal lymphadenopathy, were evaluated for each included small intestine tumor CT case. Adenocarcinomas tended to show endophytic growth, intestinal obstruction, and a heterogeneous enhancement pattern. Lymphomas tended to show exophytic growth, contrast enhancement of the intestinal tumor mucosal layer, a homogeneous enhancement pattern, and the presence of lymphadenopathies in the abdominal cavity. SCSs tended to show lobulated growth, a large cystic portion within the tumor, a heterogeneous enhancement pattern, a large size with fat stranding sign, and lower HU values in postcontrast images. Cut-off values of the minimum diameter/fifth lumbar vertebral mid-body height (≥5.80; area under the curve [AUC]=0.97, P<0.001) and minimum HU value/HU value of the aorta (≤0.26; AUC=0.96, P<0.001) were derived to discriminate SCS from the two other tumor types. In conclusion, contrast CT characteristics may be useful in differentiating small intestinal adenocarcinomas, lymphomas, and SCSs in dogs.

Diagnostic value of whole-mount crypt analysis of ileal biopsy specimens for the patients with familial small intestinal neuroendocrine tumors

Early-stage small intestinal neuroendocrine tumors (SI-NETs) are generally asymptomatic and difficult to diagnose. As a result, patients often present with late-stage incurable disease. SI-NETs originate from enterochromaffin (EC) cells, which develop enteroendocrine cell (EEC) clusters consisting of a subset of EC cells at the crypt bottom at an early stage of tumor progression. In a familial form of SI-NET, EEC clusters arise in a multifocal and polyclonal fashion. We sought to determine whether early detection and analysis of cryptal EEC clusters could provide insight into the development of SI-NETs and allow successful pre-symptomatic screening for at risk family members of patients with SI-NETs. Isolated crypts from endoscopic ileal biopsies or surgically removed specimens from 43 patients with familial SI-NET and 20 controls were formalin-fixed, immunostained for chromogranin A, and examined by confocal three-dimensional analysis for the presence of EEC cluster formations. Examination of multiple areas of macroscopic tumor-free mucosa in surgically resected specimens from patients with familial SI-NET revealed widely distributed, independent, multifocal EEC micro-tumor formations of varying sizes. Consistent with this finding, randomly sampled ileal biopsy specimens identified aberrant crypt containing endocrine cell clusters (ACECs) in patients. ACECs were found exclusively in patients (23/43, 53%) and not in controls (0/20). Furthermore, analysis of positions and numbers of EECs in crypts and ACECs indicated significant increases in EECs at the crypt bottom, predominantly at positions 0 and 1' (p < 0.0001 compared to controls), suggesting the progression of EEC accumulation below +4 position as the early process of ACEC formation. These findings also suggested that ACECs were precursors in the development of micro-tumors and subsequent macro-tumors. This study indicates that SI-NETs develop from deep crypt EC cells to become ACECs, micro-tumors, and ultimately gross tumors. This process occurs widely throughout the distal small intestine in patients with familial SI-NETs consistent with but not exclusively explained by germline disease. Finally, analysis of crypts from ileal biopsies could contribute in part to earlier diagnostic screening processes avoiding late-stage presentation of incurable disease.

Clinical Outcomes of Comprehensive Genomic Profiling Tests for Gastrointestinal Cancers: Experience from Tokushima University Hospital

In Japan, cancer genome profiling (CGP) for cancer patients without standard treatment has been covered by public insurance since June 2019. This study analyzed data of 122 patients with gastrointestinal tumors who underwent CGP to clarify cancer genome medicine's current status and possible problems at the Tokushima University Hospital. The major types of cancer included pancreatic (n=30), colorectal (n=25), biliary tract (n=15), gastric (n=11), and hepatocellular carcinoma (n=8). CGP tests included F1CDx in 70 patients (57%), F1LCDx in 36 (30%), TSO500 in 14 (11%), and NCC Oncopanel in 2 (2%). Actionable gene alterations were identified in 72 patients (59%), but only 5 patients (4%) were treated for pancreatic (n=1), colorectal (n=3), and small bowel cancers (n=1). The main reasons for not receiving genotype-matched therapy included the lack of appropriate drugs or clinical trials that matched the actionable gene alterations (n=40) and the inability to participate in clinical trials (n=10). There is still not a sufficient number of patients receiving genotype-matched treatment for gastrointestinal cancers. To promote cancer genome medicine in regional areas, attempts to improve access to genotype-matched therapies are required, as well as to promote the development of new molecular-targeted drugs and clinical trials for these drugs. J. Med. Invest. 70 : 154-159, February, 2023.

A small intestine neuroendocrine tumor: case report

Small intestinal neuroendocrine tumors (SI-NETs) are the most common small bowel tumors, they are recognized for their ability to produce hormones causing mesenteric fibrosis and carcinoid syndrome. They tend to have better surgical rate than adenocarcinomas.this work was made as an update on one of the most aggressive small intestine tumors. Presentation of case We discuss here the case of a sixth years old female woman admitted and operated for a small intestine neuroendocrine tumor with peritoneal carcinosis Discussion Neuroendocrine tumors are secreting tumors, locating mainly in the small intestine with a high malignancy risk. At the time of the diagnosis, lymph node, liver metastasis and peritoneal carcinosis are very common. Patients may be asymptomatic or consult for abdominal pain, rarely bowel obstruction, diagnosis is radiologically made and confirmed indeed histologically. Treatment involves surgery, chemotherapy, immunotherapy and radiotherapy and surveillance is assured by biomarkers, endoscopy and Octreoscan when metastatic. Conclusion The SI-NETs are rare but their incidence and prevalence have been increasing. Histologically, diagnosis is confirmed by positive immunohistochemical staining. Treatment and prognosis depend on the grade and stage of the tumor. Immunotherapy will serve as a future treatment modality.