Small Bowel Tumors Research Articles

CT FINDINGS OF MALIGNANT NEOPLASTIC MASSES OF SMALL AND LARGE INTESTINE WITH HISTOPATHOLOGICAL CORRELATION: A CROSS SECTIONAL STUDY

AIMS AND OBJECTIVES: To formulate an appropriate scanning protocol technique to evaluate malignant neoplasm of small and large intestine. To dene various CT ndings in malignant bowel neoplasm. To stage bowel neoplasm. To accurately characterize the tumour by histologic type as far as possible. Materials And Methods: In our cross-sectional study, 76 cases of small and large bowel carcinoma were referred to radiology department. After taking informed consent, CECT abdomen of the patients was done. All these patients went for surgical excision of the neoplastic mass; and the mass were sent for HPE examination. Epidemiological data, clinical features, CECT abdominal features were correlated with HPE type of the mass were found out. P-Value<0.05 was considered to be statistically signicant. Results: In Small bowel, ileum was the commonest site of involvement (5.26%), whereas sigmoid colon and rectum (18.42%) was commonest site of involvement in large bowel. Adenocarcinoma was the commonest histological subtype seen in 54 patients (71.05%), followed by lymphoma in 14 patients (18.42%), Mucinous Adenocarcinoma seen in 5 patients (57.5%). and gastrointestinal stromal tumor [GIST] seen in 3 patients(3.94%). Conclusion: Common CT imaging features in malignant bowel neoplasm are bowel Wall thickening >2cm,short Segment Involvementand heterogeneous mixed pattern. Although CT has a high specicity for detection of a metastatic lymph nodes, sensitivity is low.Liver is the commonest site of distant metastasis in malignant bowel neoplasm. Helical CT is a noninvasive, reliable, and accurate technique for imaging the liver and should be considered as the standard preoperative work-up of hepatic metastases from bowel malignant.

Disseminated, perforated gastrointestinal stromal tumour of small intestine with meckel’s diverticulitis: A case report

A case of perforated gastrointestinal stromal tumour of small intestine with Meckel’s diverticulitis causing acute abdomen is described, with a brief review of literature. A male patient presented with abdominal pain and distention, after evaluation, emergency laparotomy was done. The perforation of tumour in the ileum was found. The perforated part along with the tumour was resected and histopathological examination revealed that the tumour was gastrointestinal stromal tumour. Postoperatively the patient received Imatinib.Traditionally, the prognostic factors of these tumours are mitotic rate, tumour size and anatomic site. The complete surgical resection and use of Imatinib are the best approach.

Small intestinal myxoma presented with bowel obstruction, a rare case report.

IntroductionMyxomas are rare benign mesenchymal neoplasms and mostly occur in cardiac atrium and with lower prevalence, appear in sinonasal tract, gnathic bone, skin and joints. Benign primary tumors of the small intestine are quite unusual accounting about 3% of all the gastrointestinal tract neoplasms.Presentation of caseIn this report, we present a rare case of small intestinal myxoma in a 43-year-old man complicated by ileoileal intussusception causing bowel obstruction. The patient underwent segmental resection of small bowel and the histopathologic evaluation confirmed the diagnosis of small intestinal myxoma.DiscussionAmong benign primary neoplasms of small bowel, Solitary intestinal myxomas are extremely rare mostly locate in submucosal layer of gastric, small bowel and rarely in cecum. To our knowledge only 9 cases of small bowel myxoma is reported in the literature so far.ConclusionThis case report aware surgeons and pathologists about rare occurrence of intestinal myxomas as a differential diagnosis of intussusception.

Arterial function, biomarkers, carcinoid syndrome and carcinoid heart disease in patients with small intestinal neuroendocrine tumours

PurposeCarcinoid heart disease (CHD) is a life-threatening complication of carcinoid syndrome (CS) characterised by tricuspid regurgitation (TR). However, there is an unmet need for earlier diagnosis of CHD. We cross-sectionally assessed the prevalence and potential predictive or diagnostic markers for CS and CHD in a contemporary cohort of patients with small intestinal neuroendocrine tumours (SI-NETs).MethodsBiochemical characteristics, hepatic tumour load, measures of arterial and endothelial function, atherosclerosis, and transthoracic echocardiography were analysed in a prospective cross-sectional setting.ResultsAmong the 65 patients studied, 29 (45%) had CS (CS+ ), and 3 (5%) CHD. CS+ was characterised by significantly higher hepatic tumour load, S-5-HIAA and fP-CgA, higher frequency of diarrhoea and flushing, and more frequent PRRT compared to CS− (for all, P < 0.05). Central systolic, central mean, and central end-systolic blood pressures were significantly higher in CS+ than in CS− (for all, P < 0.05). Subjects with grades 2–4 TR had higher hepatic tumour burden, fP-CgA, and S-5-HIAA compared to those with grades 0–1 TR, but measures of vascular function did not differ. fP-CgA (P = 0.017) and S-5-HIAA (P = 0.019) but not proBNP increased significantly according to the severity of TR.ConclusionAlthough CS is common, the prevalence of CHD was found to be lower in a contemporary cohort of SI-NET patients than previously anticipated. Measures of arterial or endothelial function or carotid atherosclerosis do not identify subjects with mild TR. Echocardiography remains the most sensitive means to diagnose CHD in CS patients with high tumour burden and elevated CgA and 5-HIAA.

MicroRNA Profile of Human Small Intestinal Tumors Compared to Colorectal Tumors

Small intestinal tumors (adenoma and adenocarcinoma, SIT) are rare, and their microRNA (miRNA) expression profiles have not been established. Previously, we reported a relationship between miRNA expression profiles and the development, growth, morphology, and anticancer drug resistance of colorectal tumors. Here, we demonstrate that the miRNA expression profile of SIT is significantly different from those of tumors of the colon. We compared the onco-related miRNA expression profiles of SIT and colorectal tumors and found them to be different from each other. The expressions of miR-143 and miR-145 were frequently downregulated in SIT and colorectal tumors but not in sessile serrated adenoma/polyp tumors. The profiles of SIT and colorectal carcinomas of miR-7, miR-21, and miR-34a were considerably different. Upregulation of miR-31 expression was not found in any SIT cases. Our data suggested that miR-143 and miR-145 might act as anti-oncomirs common to adenocarcinoma of the small intestine, similar to those of colorectal adenoma and other cancers. However, the expression profiles of the other miRNAs of SIT were significantly different from those of colorectal tumors. These findings contribute useful insights into the tumor development and diagnosis of SIT.

Subsequent Primary Cancer Risk Among 5-Year Survivors of Adolescent and Young Adult Cancers.

A comprehensive examination of the incidence and mortality of subsequent primary cancers (SPCs) among adolescent and young adult (AYA) cancer survivors in the United States is lacking. Cancer incidence and mortality among 170404 cancer survivors of 5 or more years who were aged 15-39 years at first primary cancer diagnosis during 1975-2013 in 9 Surveillance, Epidemiology, and End Results registries were compared with those in the general population using standardized incidence ratio (SIR), absolute excess incidence (AEI), standardized mortality ratio (SMR), and absolute excess mortality (AEM). During a mean follow-up of 14.6 years, 13420 SPC cases and 5008 SPC deaths occurred among survivors (excluding the same site as index cancer), corresponding to 25% higher incidence (95% confidence interval [CI] = 1.23 to 1.27, AEI = 10.8 per 10 000) and 84% higher mortality (95% CI = 1.79 to 1.89, AEM = 9.2 per 10 000) than that in the general population. Overall, SPC risk was statistically significantly higher for 20 of 29 index cancers for incidence and 26 for mortality, with the highest SIR among female Hodgkin lymphoma survivors (SIR = 3.05, 95% CI = 2.88 to 3.24, AEI = 73.0 per 10 000) and the highest SMR among small intestine cancer survivors (SMR = 6.97, 95% CI = 4.80 to 9.79, AEM = 64.1 per 10 000). Type-specific SPC risks varied substantially by index cancers; however, SPCs of the female breast, lung, and colorectum combined constituted 36% of all SPC cases and 39% of all SPC deaths, with lung cancer alone representing 11% and 24% of all cases and deaths, respectively. AYA cancer survivors are almost twice as likely to die from a new primary cancer as the general population, highlighting the need for primary care clinicians to prioritize cancer prevention and targeted surveillance strategies in these individuals.

Comparative Study of the Role of Interepithelial Mucosal Mast Cells in the Context of Intestinal Adenoma-Carcinoma Progression.

Simple SummaryThe role of mast cells in the tumor microenvironment (TME) remains controversial but has become increasingly evident and explored as a possible therapeutic target. In this study, we investigated the underexplored mast cell heterogeneity of intestinal cancer by applying standardized mast cell subtyping during adenoma-carcinoma progression. We immunohistochemically evaluated and scored the occurrence of interepithelial mucosal mast cells (ieMMCs) in tumors of frequently employed genetically engineered mouse models and in human colonic adenomas and carcinomas. We found a decrease of ieMMCs from colonic low-grade adenomas to carcinomas. Moreover, mouse models based on altered Wnt signaling showed higher ieMMC scores than models based on altered MAPK signaling. Our descriptive study indicates that ieMMCs play a special role in the molecular TME related to adenoma-carcinoma progression. Furthermore, it emphasizes the need for adequate immunohistochemical methodology and experimental setup when investigating the functional role of mast cell populations of the TME.Mast cells (MCs) are crucial players in the relationship between the tumor microenvironment (TME) and cancer cells and have been shown to influence angiogenesis and progression of human colorectal cancer (CRC). However, the role of MCs in the TME is controversially discussed as either pro- or anti-tumorigenic. Genetically engineered mouse models (GEMMs) are the most frequently used in vivo models for human CRC research. In the murine intestine there are at least three different MC subtypes: interepithelial mucosal mast cells (ieMMCs), lamina proprial mucosal mast cells (lpMMCs) and connective tissue mast cells (CTMCs). Interepithelial mucosal mast cells (ieMMCs) in (pre-)neoplastic intestinal formalin-fixed paraffin-embedded (FFPE) specimens of mouse models (total lesions n = 274) and human patients (n = 104) were immunohistochemically identified and semiquantitatively scored. Scores were analyzed along the adenoma-carcinoma sequence in humans and 12 GEMMs of small and large intestinal cancer. The presence of ieMMCs was a common finding in intestinal adenomas and carcinomas in mice and humans. The number of ieMMCs decreased in the course of colonic adenoma-carcinoma sequence in both species (p < 0.001). However, this dynamic cellular state was not observed for small intestinal murine tumors. Furthermore, ieMMC scores were higher in GEMMs with altered Wnt signaling (active β-catenin) than in GEMMs with altered MAPK signaling and wildtypes (WT). In conclusion, we hypothesize that, besides stromal MCs (lpMMCs/CTMCs), particularly the ieMMC subset is important for onset and progression of intestinal neoplasia and may interact with the adjacent neoplastic epithelial cells in dependence on the molecular environment. Moreover, our study indicates the need for adequate GEMMs for the investigation of the intestinal immunologic TME.

Gastrointestinal Stromal Tumor of the Proximal Small Intestine Revealed by Hemorrhagic Shock: About 02 Cases and Review of the Literature

Gastrointestinal stromal tumors are mesenchymal tumors that represent 0.1% to 0.3% of all malignant tumors. Their clinical presentation is nonspecific but presentation by massive hemorrhage with hemodynamic instability is rare. We report the cases of 02 young patients who presented a fulminant digestive hemorrhage with hemodynamic instability and whose endoscopic exploration did not reveal any obvious etiology. That’s why we involved interventional radiology and surgical team in order to localize and confirm the diagnosis of a hemorrhagic jejunal GIST and then to ensure the hemostasis by small bowel resection taking away the jejunal tumor.

Survival According to Therapy Regimen for Small Intestinal Neuroendocrine Tumors

Introduction: Scarce data exist for therapy regimens other than somatostatin analogues (SSA) and peptide receptor radiotherapy (PRRT) for siNET. We analyzed real world data for differences in survival according to therapy. Patients and methods: Analysis of 145 patients, diagnosed between 1993 and 2018 at a single institution, divided in treatment groups. Group (gr.) 0: no treatment (n = 10), gr 1: TACE and/or PRRT (n = 26), gr. 2: SSA (n = 32), gr. 3: SSA/PRRT (n = 8), gr. 4: chemotherapy (n = 8), gr. 5: not metastasized (at diagnosis), surgery only (n = 53), gr. 6 = metastasized (at diagnosis), surgery only (n = 10). Results: 45.5% female, median age 60 years (range, 27–84). A total of 125/145 patients with a resection of the primary tumor. For all patients, 1-year OS (%) was 93.8 (95%-CI: 90–98), 3-year OS = 84.3 (CI: 78–90) and 5-year OS = 77.5 (CI: 70–85). For analysis of survival according to therapy, only stage IV patients (baseline) that received treatment were included. Compared with reference gr. 2 (SSA only), HR for OS was 1.49 (p = 0.47) for gr. 1, 0.72 (p = 0.69) for gr. 3, 2.34 (p = 0.19) for gr. 4. The 5 y OS rate of patients whose primary tumor was resected (n = 125) was 73.1%, and without PTR was 33.3% (HR: 4.31; p = 0.003). Individual patients are represented in swimmer plots. Conclusions: For stage IV patients in this analysis (limited by low patient numbers in co. 3/4), multimodal treatment did not significantly improve survival over SSA treatment alone. A resection of primary tumor significantly improves survival.

Immunogenetics of gastrointestinal cancers: A systematic review and retrospective survey of inborn errors of immunity in humans.

Humans with inborn errors of immunity (IEI), or primary immunodeficiencies, may be associated with a potential risk factor for early-onset gastrointestinal (GI) cancer. We systematically reviewed all cases with clinical diagnoses of both an IEI and a GI cancer in three databases (MEDLINE, SCOPUS, and EMBASE). In total, 76 publications satisfying our inclusion criteria were identified, and data for 149 cases were analyzed. We also searched our institutional cancer registry for such cases. We identified 149 patients with both an IEI and a GI cancer, 95 presented gastric cancer, 13 small bowel cancer, 35 colorectal cancer, and 6 had an unspecified cancer or cancer at another site. Gastric and colon adenocarcinomas were the most common. For both gastric and colorectal cancers, age at onset was significantly earlier in patients with IEIs than in the general population, based on the SEER database. Common variable immunodeficiency (CVID) was the most common IEI associated with gastrointestinal cancer. About 12% of patients had molecular genetic diagnoses, the three most frequently implicated genes being ATM, CARMIL2, and CTLA4. Impaired humoral immunity and Epstein-Barr virus (EBV) infection were frequently reported as factors potentially underlying early-onset GI cancers in patients with IEIs. We identified one patient with CVID and early-onset gastric adenocarcinoma, recurrent diarrhea, and gastrointestinal CMV infection from a retrospective survey. Patients with IEIs should be considered at risk of early-onset GI cancers and should therefore undergo cancer screening at an earlier age.

Gastrointestinal stromal tumors with Kit gene mutation in 4 guinea pigs (Cavia porcellus).

Gastrointestinal stromal tumors (GISTs) have been rarely reported in guinea pigs. We aimed to characterize the clinical and pathological features of GISTs in 4 guinea pigs and investigate the presence of mutations in exon 11 of the KIT proto-oncogene receptor tyrosine kinase (Kit) gene. Two subjects were male and 2 were female; 2 were 6 years old, 1 was 7 years old, and 1 was of an unknown age. Three cases had primary gastric tumors, whereas 1 had a primary small intestinal tumor. All cases had tumors that extended from the submucosa to the serosa with extraluminal growth. A gastric tumor had gastric, pancreatic, and cecal metastases. Histologically, the tumors were sharply demarcated and composed of spindle cells arranged in bundles, intermixed with small amounts of collagenous stroma. The tumor cells had mild atypia with few mitotic figures (0-5/50 high power fields, 7.95 mm2) and were immunolabeled for KIT and Discovered-on-GIST 1 (DOG1). All cases had mutations in exon 11 of the Kit gene. These findings indicate that GISTs in guinea pigs are similar to those in humans and dogs. GISTs in guinea pigs are potentially malignant submucosal tumors with KIT- and DOG1-immunolabeling, exon 11 KIT mutations, and the possibility of metastasis.

Extracolonic tumours in a pedigree with EPCAM-related Lynch Syndrome

Lynch Syndrome is characterized by phenotypic and genotypic heterogeneity. Despite scarce evidence, individuals with an EPCAM deletion appear to have a comparable risk of colorectal cancer (CRC) as MSH2 mutation carriers, but a lower risk of extracolonic cancer (such as endometrial cancer) unless the deletion extends close to the promoter of MSH2.A genotype-phenotype correlation is yet to be established for EPCAM alterations. In this report, we describe a family with EPCAM deletion characterized by a particularly aggressive phenotype and extracolonic cancer.We present a family with 5 members carrying an EPCAM deletion encompassing exons 8 and 9. Three female family members presented CRC at the ages of 32, 44 and 60 (mucinous moderately and well-differentiated adenocarcinoma); in two of them metachronous colon cancers and advanced adenomas were diagnosed in the intensive surveillance program.Two female patients (42 and 63 years-old) presented with gastric cancer (GC). Two patients presented with small bowel cancer at 51 and 60 years-old - the first one presented a metachronous jejunal cancer at 68 years. Only one family member was submitted to hemithyroidectomy due a right-lobe Hürthle cell carcinoma at 56 years-old.This report illustrates the existence of intrafamilial clinical heterogeneity among carriers of this EPCAM alteration, and hence the difficulty in predicting phenotype for EPCAM-associated Lynch syndrome.

Case report: successful treatment of a rare large jejunal gastrointestinal stromal tumour with surgery and using principle of short-term fasting

Small intestinal gastrointestinal stromal tumours (GISTs) are rare mesenchymal tumours of gastrointestinal tract comprise 0.04% of small intestinal neoplasms. We presented a case of 61 years female presenting in emergency with pain in epigastrium, multiple episodes of vomiting, raised total leucocyte counts. CECT abdomen showed a large non-enhancing jejunal lesion. The patient had emergency small bowel resection and anastomosis. Postoperative patient started on imatinib and kept on short-term fasting. This case report highlights the rare presentation of jejunal GISTs, successful surgical outcome and good enhancing effect of short-term fasting on chemotherapy.

Early age of onset and broad cancer spectrum persist in MSH6- and PMS2-associated Lynch syndrome

PurposeThis study aimed to characterize MSH6/PMS2-associated mismatch repair–deficient (MMR-D)/microsatellite instability-high (MSI-H) tumors, given revised guidelines suggesting more modest phenotypes. MethodsPatients who consented to Institutional Review Board–approved protocols of tumor/germline sequencing or Lynch syndrome registry at a single institution from February 2005 to January 2021 with germline, heterozygous MSH6/PMS2 pathogenic/likely pathogenic variants were identified. Clinical data were abstracted and correlated with MMR/microsatellite instability status using nonparametric tests. ResultsWe identified 243 patients (133 sequencing, 110 registry) with germline MSH6/PMS2 pathogenic/likely pathogenic variants; 186 (77%) had >1 cancer. Of 261 pooled tumors, colorectal cancer (CRC) and endometrial cancer (EC) comprised 55% and 43% of cancers in MSH6 and PMS2, respectively; 192 tumors underwent molecular assessments and 122 (64%) were MMR-D/MSI-H (77 in MSH6, 45 in PMS2). MMR-D/MSI-H cancers included CRC (n = 56), EC (n = 35), small bowel cancer (n = 6), ovarian cancer (n = 6), urothelial cancer (n = 5), pancreas/biliary cancer (n = 4), gastric/esophageal cancer (n = 3), nonmelanoma skin tumors (n = 3), prostate cancer (n = 2), breast cancer (n = 1), and central nervous system/brain cancer (n = 1). Among MMR-D/MSI-H CRC and EC, median age of diagnosis was 51.5 (range = 27-80) and 55 (range = 39-74) years, respectively; 9 of 56 (16%) MMR-D/MSI-H CRCs were diagnosed at age <35 years. ConclusionMSH6/PMS2 heterozygotes remain at risk for a broad spectrum of cancers, with 16% of MMR-D/MSI-H CRCs presenting before upper threshold of initiation of colonoscopy per guidelines.

Landscape of KRASG12C, Associated Genomic Alterations, and Interrelation With Immuno-Oncology Biomarkers in KRAS-Mutated Cancers.

PURPOSEPromising single-agent activity from sotorasib and adagrasib in KRASG12C-mutant tumors has provided clinical evidence of effective KRAS signaling inhibition. However, comprehensive analysis of KRAS-variant prevalence, genomic alterations, and the relationship between KRAS and immuno-oncology biomarkers is lacking.MATERIALS AND METHODSRetrospective analysis of deidentified records from 79,004 patients with various cancers who underwent next-generation sequencing was performed. Fisher's exact test evaluated the association between cancer subtypes and KRAS variants. Logistic regression assessed KRASG12C comutations with other oncogenes and the association between KRAS variants and immuno-oncology biomarkers.RESULTSOf the 79,004 samples assessed, 13,758 (17.4%) harbored KRAS mutations, with 1,632 (11.9%) harboring KRASG12C and 12,126 (88.1%) harboring other KRAS variants (KRASnon-G12C). Compared with KRASnon-G12C across all tumor subtypes, KRASG12C was more prevalent in females (56% v 51%, false discovery rate-adjusted P value [FDR-P] = .0006), current or prior smokers (85% v 56%, FDR-P < .0001), and patients age > 60 years (73% v 63%, FDR-P ≤ .0001). The most frequent KRAS variants across all subtypes were G12D (29.5%), G12V (23.0%), G12C (11.9%), G13D (6.5%), and G12R (6.2%). KRASG12C was most prevalent in patients with non–small-cell lung cancer (9%), appendiceal (3.9%), colorectal (3.2%), tumor of unknown origin (1.6%), small bowel (1.43%), and pancreatic (1.3%) cancers. Compared with KRASnon-G12C-mutated, KRASG12C-mutated tumors were significantly associated with tumor mutational burden-high status (17.9% v 8.4%, odds ratio [OR] = 2.38; FDR-P < .0001). KRASG12C-mutated tumors exhibited a distinct comutation profile from KRASnon-G12C-mutated tumors, including higher comutations of STK11 (20.59% v 5.95%, OR = 4.10; FDR-P < .01) and KEAP1 (15.38% v 4.61%, OR = 3.76; FDR-P < .01).CONCLUSIONThis study presents the first large-scale, pan-cancer genomic characterization of KRASG12C. The KRASG12C mutation was more prevalent in females and older patients and appeared to be associated with smoking status. KRASG12C tumors exhibited a distinct comutation profile and were associated with tumor mutational burden-high status.

Systematic Evaluation of the Immune Environment of Small Intestinal Neuroendocrine Tumors.

The immune tumor microenvironment and the potential therapeutic opportunities for immunotherapy in small intestinal neuroendocrine tumors (siNET) have not been fully defined. Herein, we studied 40 patients with primary and synchronous metastatic siNETs, and matched blood and normal tissue obtained during surgery. We interrogated the immune checkpoint landscape using multi-parametric flow cytometry. In addition, matched FFPE tissue was obtained for multi-parametric IHC to determine the relative abundance and distribution of T-cell infiltrate. Tumor mutational burden (TMB) was also assessed and correlated with immune infiltration. Effector tumor-infiltrating lymphocytes (TIL) had a higher expression of PD-1 in the tumor microenvironment compared with the periphery. In addition, CD8+ TILs had a significantly higher co-expression of PD-1/ICOS and PD-1/CTLA-4 (cytotoxic T lymphocyte antigen-4) and higher levels of PD-1 expression compared with normal tissue. IHC revealed that the majority of cases have ≤10% intra-tumoral T cells but a higher number of peri-tumoral T cells, demonstrating an "exclusion" phenotype. Finally, we confirmed that siNETs have a low TMB compared with other tumor types in the TCGA database but did not find a correlation between TMB and CD8/Treg ratio. Taken together, these results suggest that a combination therapy approach will be required to enhance the immune response, using PD-1 as a checkpoint immunomodulator backbone in combination with other checkpoint targeting molecules (CTLA-4 or ICOS), or with drugs targeting other pathways to recruit "excluded" T cells into the tumor microenvironment to treat patients with siNETs.

Synchronous Neoplasms of the Small Bowel: A Diagnostic Challenge.

Small bowel tumours are rare, representing about 0.5% of all tumours and about 3% of gastrointestinal tract tumours. The low prevalence contrasts with the vast surface area of the small intestine, which accounts for over 90% of the surface area of the digestive tract. The frequency of small tumours decreases from proximal to distal, and therefore from the duodenum to the ileum. The histological types differ in terms of prevalence according to the affected segment, with adenocarcinoma being the most frequent in the duodenum and jejunum and carcinoid tumour in the ileum. Diagnosis is challenging due to clinical non-specificity, low prevalence and a low level of suspicion.Schwannomas are typically benign tumours that arise from Schwann’s cells and are rarely found in the small intestine. It is even more rare to find them together with another histological type, namely adenocarcinoma. No cases have been reported in the literature of these lesions occurring in the small intestine simultaneously. Further studies are needed to clarify the underlying pathophysiology of these synchronous tumours.The authors present the case of an 86-year-old female patient admitted for high intestinal subocclusion, with refractory vomiting and involuntary weight loss. Two synchronous lesions in the digestive tract were identified: an adenocarcinoma in the duodenum and a schwannoma in the ileum. The patient underwent surgical resection of both lesions.A high level of suspicion combined with a multidisciplinary approach is necessary for timely diagnosis and surgical resolution.LEARNING POINTSSmall bowel neoplasms are rare and clinically non-specific; in addition, diagnosis is difficult due to imaging artifacts and tumour inaccessibility for biopsy for definitive histological diagnosis.Gastrointestinal schwannomas are rare and the pathophysiology of synchrony with other histological subtypes remains to be clarified.A multidisciplinary approach from the beginning is important for a timely diagnosis and better outcome.

Recent trends in the morbidity and mortality in patients with familial adenomatous polyposis: a retrospective single institutional study in Japan.

This study aimed to assess current trends in morbidity and mortality among patients with familial adenomatous polyposis (FAP). These data can be used for optimal surveillance and management of such patients. Data (November 2001 and April 2020) of genetically confirmed patients with FAP (n = 87) and their first-degree relatives with FAP phenotype (n = 20) were extracted from the Saitama Medical Center database. Standardized mortality ratio (SMR) and standardized incidence ratio (SIR) were estimated using indirect method. Overall, 46 men and 61 women were included; the median age at FAP diagnosis was 28.0years for both. The SMR for all causes of death was 47.7 (95% confidence interval [CI] 19.1-98.2) in women and 26.5 (95% CI 9.73-57.8) in men. The SIR for colorectal cancer (CRC) was 860 (95% CI 518-1340) in women and 357 (95% CI 178-639) in men. The SMR for CRC was 455 (95% CI 93.7-1330) in women and 301 (95% CI 62.0-879) in men. Thirteen patients died during the observation period, and CRC was the leading cause of death (46%). Other causes of death included desmoid tumor (n = 2), small intestinal cancer (n = 2), ovarian cancer (n = 1), duodenal cancer (n = 1), and sepsis (n = 1). The mortality ratio, estimated using SMR, remained high. CRC was the leading cause of death, whereas almost half of the causes of deaths were extra-colonic tumors. Life-long management of extra-colonic diseases may improve the prognosis in these patients.

KRAS Mutation in Rare Tumors: A Landscape Analysis of 3453 Chinese Patients.

KRAS is the most commonly mutated oncogene in human cancers. Targeted therapy and immunotherapy for this gene have made remarkable progress in recent years. However, comprehensive molecular landscape analysis of KRAS in rare tumors is lacking. Retrospective analysis was performed on clinical samples from patients with rare tumors collected between September 2015 and September 2021, using hybrid-capture-based next-generation sequencing for genomic profiling and immunohistochemistry assay for PD-L1. Of the 3,453 patients included in analysis, KRAS mutations were identified in 8.7% patients in overall; mutation rate and mutation subtypes varied widely across tumor systems and subtypes. KRAS mutations included 21 missense mutations, of which G12D (29.2%), G12V (24.6%), and G13D (10.8%) were most common. Interestingly, KRAS G12C was observed in 0.6% patients overall, and in 5.7% of sarcomatoid carcinoma of the lung and 5.4% of clear cell ovarian cancer tumors, but none in small-bowel cancer tumors. 31.8% KRAS mutations and 36.4% KRAS G12C mutations co-occurred with other targetable alterations. No significant correlation was observed between TMB-H, MSI-H, PD-L1 status, and KRAS mutation status, which may be related to the high proportion of G12D. This study is the first KRAS mutation landscape study in rare tumors of large sample size in China and worldwide. Our results suggest that targeted therapy and immunotherapy are both feasible, albeit complex, in these patients. This information may have significant impact on the operation of clinical trials for rare tumor patients with KRAS mutations in China.

Aberrant tryptophan metabolism in stromal cells is associated with mesenteric fibrosis in small intestinal neuroendocrine tumors.

BackgroundIncreased levels of serotonin secretion are associated with mesenteric fibrosis (MF) in small intestinal neuroendocrine tumors (SI-NETs). However, the profibrotic potential of serotonin differs between patients, and in this study, we aimed to gain an understanding of the mechanisms underlying this variability. To this end, we analyzed the proteins involved in tryptophan metabolism in SI-NETs.MethodsProteomes of tumor and stroma from primary SI-NETs and paired mesenteric metastases of patients with MF (n = 6) and without MF (n = 6) were identified by liquid chromatography–mass spectrometry (LC-MS). The differential expression of proteins involved in tryptophan metabolism between patients with and without MF was analyzed. Concurrently, monoamine oxidase A (MAO-A) expression was analyzed in the tumor and stromal compartment by immunohistochemistry (IHC) and reported as intensity over area (I/A).ResultsOf the 42 proteins involved in tryptophan metabolism, 20 were detected by LC-MS. Lower abundance of ten proteins was found in mesenteric metastases stroma in patients with MF. No differential expression was found in primary SI-NETs. In patients with MF, IHC showed lower MAO-A expression in the stroma of the primary SI-NETs (median 4.2 I/A vs 6.5 I/A in patients without MF, P = 0.003) and mesenteric metastases (median 2.1 I/A vs 2.8 I/A in patients without MF, P= 0.019).ConclusionWe found a decreased expression of tryptophan and serotonin-metabolizing enzymes in the stroma in patients with MF, most notably in the mesenteric stroma. This might account for the increased profibrotic potential of serotonin and explain the variability in the development of SI-NET-associated fibrotic complications.