Adenocarcinoma Of Small Intestine Research Articles

The mutational landscape of upper gastrointestinal adenocarcinomas- A study of similarities and differences

PurposeThe gastrointestinal tract is home to a wide variety of neoplasms. Gastrointestinal adenocarcinomas display distinct prognostic patterns. With the advent of next generation sequencing, attempts are being made to delineate distinct molecular characteristics of these adenocarcinomas from adjoining anatomical sites. MethodsThirty-seven cases of upper gastrointestinal adenocarcinomas including those of the esophagus, gastroesophageal junction, stomach, small intestine and gallbladder were retrieved. Next generation sequencing data consisting of base substitutions, copy number variations, indels and rearrangements, in 324 genes, were analyzed for recurrent genetic abnormalities. Statistical analysis was performed using IBM SPSS25 and SAS software. ResultsGenetic alterations were found in 181 genes. APC mutations were found in 50% of the esophageal adenocarcinomas, 5% of the gastric adenocarcinomas and 33.3% of the small intestinal adenocarcinomas (p = 0.04). PIK3 gene family mutations were found in 10% of the gastric adenocarcinomas, 66% of the gall bladder adenocarcinomas and 66% of the small intestinal adenocarcinomas (p = 0.002). The mutations were found exclusively in the PIK3 class 1 family. TP53 mutations were more common in tumors with intact DNA mismatch repair protein expression as assessed by immunohistochemistry (p = 0.042). ConclusionIn this study, APC gene mutations were found to be more frequent in esophageal and small intestinal adenocarcinomas than previously reported. PIK3 class 1 gene family mutations were found to be more frequent in gallbladder and small intestinal adenocarcinomas. An inverse relationship was found between TP53 mutations and loss of DNA mismatch repair protein expression.

Sox9, Hopx, and survivin and tuft cell marker DCLK1 expression in normal canine intestine and in intestinal adenoma and adenocarcinoma.

Self-renewal of the intestinal epithelium originates from stem cells located at the crypt base. Upregulation of various stem cell markers in intestinal epithelial neoplasms indicates a potential role of stem cells in tumorigenesis. In this study, the immunoreactivity of potential intestinal stem cell markers (Sry box transcription factor 9 [Sox9], homeodomain-only protein [Hopx], survivin) and tuft cell marker doublecortin-like kinase 1 (DCLK1) in normal canine intestine and intestinal epithelial neoplasms was investigated. Formalin-fixed paraffin-embedded (FFPE) small and large intestine as well as intestinal neoplasms (55 colorectal adenomas [CRAs], 17 small intestinal adenocarcinomas [SICs], and 12 colorectal adenocarcinomas [CRCs]) were analyzed immunohistologically. Potential stem cell markers Sox9, Hopx, and survivin were detected in the crypts of normal canine small and large intestine. DCLK1+ tuft cells were present in decreasing numbers along the crypt-villus axis of the jejunum and rarely detectable in large intestine. In canine intestinal epithelial tumors, nuclear Sox9 immunoreactivity was detectable in 84.9% (CRA), 80% (CRC), and 77% of epithelial neoplastic cells (SIC). Hopx and survivin were expressed within cytoplasm and nuclei of neoplastic cells in benign and malignant tumors. DCLK1 showed a cytoplasmic reaction within neoplastic cells. The combined score of Hopx, DCLK1, and survivin varied among the examined cases. Overall, malignant tumors showed lower DCLK1 scores but higher Hopx scores in comparison with benign tumors. For survivin, no differences were detectable. In conclusion, stem cell markers Sox9, Hopx, and survivin were detectable at the crypt base and the immunoreactivity of Sox9, DCLK1, survivin, and Hopx was increased in canine intestinal adenomas and adenocarcinomas compared with normal mucosa.

Determination of the structure and in vitro anticancer activity of fucan from Saccharina dentigera and its derivatives

The fucoidan SdeF was isolated from brown alga Saccharina dentigera. The structure of the obtained polysaccharide was studied by chemical methods, NMR spectroscopy of the fully and partially desulfated derivatives, and mass spectrometry of the fucoidan fragments, labeled with 18O. The SdeF was shown to be sulfated (40%) 1,3-linked α-L-fucan, with branches at C2. The sulfate groups were found at positions C2 and C4. Derivatives SdeFDS and SdeFPL were obtained by solvolytic desulfation and autohydrolysis of SdeF, respectively. According to 13C NMR data, SdeFDS is 1,3-linked α-L-fucan, while SdeFPL is 4-sulfated 1,3-linked α-L-fucan. Native fucoidan SdeF was shown to be a non-toxic anticancer substance in the model of human malignant melanoma RPMI-7951, colorectal adenocarcinoma HCT-116, and small intestine adenocarcinoma HuTu 80 cells. The partial desulfation of SdeF at C2 and/or the reduction of its Mw, from 229 to 28 kDa, decreased the anticancer activity; complete removal of the sulfated groups and/or Mw reduction to 4.7 kDa further reduced the effect of this polysaccharide.

Outcomes of patients with small intestine adenocarcinoma (SIA) in a Canadian province: A population-based cohort study.

641 Background: SIA is a rare cancer. Limited data is available about clinicopathological factors and interventions that correlate with its outcomes. The current study aims to determine outcomes of patients with SIA who were diagnosed in a Canadian province. Methods: In this retrospective population-based cohort study patients with biopsy proven SIA diagnosed during 2008-2017 in the province of Saskatchewan were assessed. A Cox Proportional multivariate regression analysis was performed to determine correlation between survival and exploratory factors. Results: 112 eligible patients with median age of 73 yrs and M:W 53: 59 were identified. 75% had a comorbid illness, 34% had a secondary cancer and 45% had WHO performance status (PS) < 2. Of 112 patients, 51 (46%) had early-stage disease and 61 (54%) had advanced-stage disease. Median neutrophil: lymphocyte (NLR) was 4.5. The median overall survival (mOS) in relation to stage of the disease were as follow: stage 1, 59 months, stage 2, 30 months, stage 3, 20 months and stage 4, 3 months (P < 0.001). The patients with early-stage disease had mOS of 36.0 months (95% CI: 8.0-64.0) vs. 3.0 months (1.74-4.26) with advanced disease (P < 0.0001). Of 21 patients with stage 3 disease their median disease-free survival was 26 months (23.1-28.9) with chemotherapy vs. 4 months (0.0-9.1) with no chemotherapy, p = 0.04. Patients with stage 4 disease who had surgery and or chemotherapy had mOS of 18 months (13.70-23.32) vs. 4 months (2.20-5.82) with chemotherapy alone p = 0.03. On univariate analysis age ≥70 yrs, WHO PS > 1, stage 4 disease, low albumin, elevated creatinine, high alkaline phosphatase, duodenal cancer, lack of surgery, and NLR of > 4.50 were significantly correlated with inferior survival. On multivariate analysis stage 4 disease, HR, 3.20 (95%CI:1.84-5.40), WHO PS > 1, HR, 2.22 (1.42-3.45), no surgery, HR, 2.10 (1.25-3.50), and NLR > 4.5, HR, 1.72 (1.10-2.71) were significantly correlated with inferior survival. Conclusions: Most patients with SIA were diagnosed with advanced-stage. In addition to advanced-stage disease and poor PS, lack of surgery and baseline LNR of > 4.5 were significantly correlated with inferior survival.

Loss of MMR and TGFBR2 Increases the Susceptibility to Microbiota-Dependent Inflammation-Associated Colon Cancer.

Background and AimsMutations in DNA mismatch repair (MMR) genes are causative in Lynch syndrome and a significant proportion of sporadic colorectal cancers (CRCs). MMR-deficient (dMMR) CRCs display increased mutation rates, with mutations frequently accumulating at short repetitive DNA sequences throughout the genome (microsatellite instability). The TGFBR2 gene is one of the most frequently mutated genes in dMMR CRCs. Therefore, we generated an animal model to study how the loss of both TGFBR2 signaling impacts dMMR-driven intestinal tumorigenesis in vivo and explore the impact of the gut microbiota.MethodsWe generated VCMsh2/Tgfbr2 mice in which Msh2loxP and Tgfbr2loxP alleles are inactivated by Villin-Cre recombinase in the intestinal epithelium. VCMsh2/Tgfbr2 mice were analyzed for their rate of intestinal cancer development and for the mutational spectra and gene expression profiles of tumors. In addition, we assessed the impact of chemically induced chronic inflammation and gut microbiota composition on colorectal tumorigenesis.ResultsVCMsh2/Tgfbr2 mice developed small intestinal adenocarcinomas and CRCs with histopathological features highly similar to CRCs in Lynch syndrome patients. The CRCs in VCMsh2/Tgfbr2 mice were associated with the presence of colitis and displayed genetic and histological features that resembled inflammation-associated CRCs in human patients. The development of CRCs in VCMsh2/Tgfbr2 mice was strongly modulated by the gut microbiota composition, which in turn was impacted by the TGFBR2 status of the tumors.ConclusionsOur results demonstrate a synergistic interaction between MMR and TGFBR2 inactivation in inflammation-associated colon tumorigenesis and highlight the crucial impact of the gut microbiota on modulating the incidence of inflammation-associated CRCs.

Olfactomedin 4 Is Not a Precise Marker for Human Intestinal Stem Cells, But Is Involved in Intestinal Carcinogenesis

Olfactomedin 4 Is Not a Precise Marker for Human Intestinal Stem Cells, But Is Involved in Intestinal Carcinogenesis

Prognostic Value of LC3B and p62 Expression in Small Intestinal Adenocarcinoma.

Autophagy, a mechanism that maintains cellular homeostasis, is involved in tumor cell growth and survival in cancer, and autophagy inhibitors have been tested clinical trials for anticancer therapy. To elucidate the clinical and prognostic implications of autophagy in small intestinal adenocarcinoma (SIAC), we assessed the expression of autophagy markers, LC3B and p62, in 171 surgically resected primary SIACs using automated quantitative analysis. Positive LC3B, p62 nuclear (p62Nu), and p62 cytoplasmic (p62Cy) expression was observed in 23 (13.5%), 52 (30.4%), and 43 (25.1%) carcinomas, respectively. LC3B+ expression was correlated with undifferentiated carcinoma (p < 0.001) and high histologic grade (p = 0.029). The combined expression of LC3B and p62Nu (LC3+/p62Nu+) was related to the older age of patients (p = 0.017), undifferentiated carcinoma (p < 0.001), and high grade (p = 0.031). LC3B+ (p = 0.006), p62Cy+ (p = 0.041), or p62Nu+ (p = 0.006) expression were associated with worse survival. In addition, SIAC patients with either LC3B+/p62Nu+ (p = 0.001) or LC3B+/p62Cy+ (p = 0.002) expression had shorter survival times. In multivariate analysis, LC3B expression remained an independent prognostic factor (p = 0.025) for overall survival. In conclusion, autophagy may play a role in the tumorigenesis of SIACs, and LC3B and p62 could be used as prognostic biomarkers and potential therapeutic targets for SIACs.

OLFM4-RET fusion is an oncogenic driver in small intestine adenocarcinoma.

Small intestine adenocarcinoma is a rare intestinal malignancy with distinct clinical, pathological, and molecular characteristics. Recently, a fusion of the intestinal stem-cell marker olfactomedin 4 (OLFM4) and the proto-oncogene RET has been identified in a small intestine adenocarcinoma patient. Here we investigated the biological effects of OLFM4-RET fusion and whether it can initiate tumorigenesis in small intestine. OLFM4 expression was found to be frequently lost or reduced in human small intestine adenocarcinoma, and its downregulation correlated with high tumor grade and advanced tumor stage. Expression of OLFM4-RET fusion-induced cellular transformation in HEK293 cells and blocked RET-induced inhibition of colony growth in HuTu 80 small intestine adenocarcinoma cells. Further, expression of OLFM4-RET activated the RAS-RAF-MAPK and STAT3 cell signaling pathways in both HEK293 cells and HuTu 80 cells. OLFM4-RET expression in HEK293 cells upregulated multiple families of genes related to carcinogenesis, cancer progression, and metastasis. Targeted expression of OLFM4-RET in the small intestine led to the development of hyperplasia, adenoma, or adenocarcinoma in transgenic mice. Our study suggests that OLFM4-RET is an oncogenic driver of small intestine tumorigenesis. Therefore, the small intestine adenocarcinoma patients with OLFM4-RET fusion may benefit from treatment with RET kinase inhibitor.

S3047 Small Intestinal Adenocarcinoma: Rarely Considered, Often Missed on Endoscopy

S3047 Small Intestinal Adenocarcinoma: Rarely Considered, Often Missed on Endoscopy

WNT2 activation through proximal germline deletion predisposes to small intestinal neuroendocrine tumors and intestinal adenocarcinomas.

Many hereditary cancer syndromes are associated with an increased risk of small and large intestinal adenocarcinomas. However, conditions bearing a high risk to both adenocarcinomas and neuroendocrine tumors are yet to be described.We studied a family with 16 individuals in four generations affected by a wide spectrum of intestinal tumors, including hyperplastic polyps, adenomas, small intestinal neuroendocrine tumors, and colorectal and small intestinal adenocarcinomas.To assess the genetic susceptibility and understand the novel phenotype, we utilized multiple molecular methods, including whole genome sequencing, RNA sequencing, single cell sequencing, RNA in situ hybridization and organoid culture.We detected a heterozygous deletion at the cystic fibrosis locus (7q31.2) perfectly segregating with the intestinal tumor predisposition in the family. The deletion removes a topologically associating domain border between CFTR and WNT2, aberrantly activating WNT2 in the intestinal epithelium. These consequences suggest that the deletion predisposes to small intestinal neuroendocrine tumors and small and large intestinal adenocarcinomas, and reveals the broad tumorigenic effects of aberrant WNT activation in the human intestine.

Specific survival nomograms based on SEER database for small intestine adenocarcinoma.

Small intestine cancers, as an extremely rare tumor type, account only for 3% of all gastrointestinal tumors. Small intestine adenocarcinoma (SIA), representing approximately one-third of all small bowel cancers, has received relatively little attention, both in research efforts and clinical cognizance. Owing to anatomical proximity and rarity, small bowel adenocarcinomas are frequently grouped with colorectal adenocarcinomas. Therefore, a large SIA patient cohort is needed to develop and validate new nomogram prognostic models specific to SIA patients. Patients diagnosed with SIA between 2004 and 2016 were extracted from the Surveillance, Epidemiology, and Final Results (SEER) database. All patients were randomly assigned to the training cohort and the validation cohort (2:1). The basic clinical information, detailed pathological staging, and treatment information of the patients were included in the analysis. Nomograms were shaped following the evaluations of the Cox regression model and verified using the decision curve analysis (DCA), time-dependent receiver operating characteristic (ROC) curves, concordance index (C-index), and calibration curves. The entire group comprised 6,947 patients with small intestine adenocarcinoma. According to the results of the multivariate Cox regression analysis, ten variables, including marital status, age, pathological grade, tumor location, T (tumor), N (nodes), M (metastasis) stage, surgery, chemotherapy, and regional nodes examined (RNE), were independent predictors of both of overall survival (OS) and cancer-specific survival (CSS). All significant variables were used to create the nomograms for OS and CSS. Various methods verified the reliability of the nomograms. The C-indexes of the OS and CSS nomogram were 0.756 (95% CI, 0.748-0.764) and 0.771 (95% CI, 0.761-0.781) in the training cohort and 0.748 (95% CI, 0.736-0.760) and 0.767 (95% CI, 0.752-0.781) in the validation cohort. The calibration curve showed good agreement between the nomogram prediction and actual survival. DCA indicated a clear net benefit of these new forecasting models. This study built and verified nomograms to predict OS and CSS for rare SIA, which appear to be excellent tools to augment the clinically available evidence to facilitate the discussion between SIA patients and clinicians regarding therapeutic choice.

Small Intestinal Adenocarcinomas Arising in Enteritis Cystica Profunda With Metaplasia: A Report of 2 Cases.

Enteritis cystica profunda (ECP) is an uncommon benign condition arising after mucosal damage. We describe 2 cases of small intestinal adenocarcinomas associated with ECP at the distal ileum, one in a background of active Crohn ileitis (case 1), the other 22 years after pelvic radiation therapy (case 2). Both patients presented with small bowel obstruction and received ileocectomy. Macroscopic examination identified an indurated/strictured area in the distal ileum. Histologically, both cases showed a low-grade tubuloglandular adenocarcinoma arising in a background of chronic ischemic stricture and ECP lined by flat cuboidal cells with mild cytologic atypia resembling pancreatobiliary-type epithelium. There was no conventional dysplasia in the surface or adjacent mucosa. Immunohistochemically, both ECP with metaplasia and invasive carcinomas were diffusely positive for CK7 and CK19, while focally positive for CDX2 or CK20. Both cases showed normal wild-type p53 expression. Case 2 was also mismatch repair protein proficient, with membranous β-catenin staining, and retained nuclear SMAD4 expression. In summary, the 2 cases uniquely exhibits "enteritis-metaplasia-carcinoma" sequence, which has not been reported before. This process appears to bypass conventional dysplasia, be slow and indolent, independent of p53, APC/β-catenin, and SMAD4/TGFβ signaling pathways.

CDH17+/CDX2+ Can be Helpful in Providing Support for Small Intestinal Origin Versus Pancreatic or Biliary Origin.

Because of the distinct and complex anatomy of the ampullary region, the exact origin of the periampullary tumors was often difficult to ascertain. In this study, we evaluated 78 patient samples, including 26 small intestinal adenocarcinomas, 35 pancreatic ductal adenocarcinomas, and 17 cholangiocarcinomas by immunohistochemical detection of cadherin-17 (CDH17), CDX2, CK20, and CK19 protein expression. The result showed that CDH17 and CDX2 expression was higher in small intestinal adenocarcinoma (73.1% and 65.4%) than in pancreatic (14.3% and 2.9%) and bile duct (41.2% and 23.5%) cancers, respectively. CK20 expression was low in 78 tumor tissues, but relatively high in small intestinal adenocarcinoma (42.3%). CK19 showed a strong positive expression in all 78 adenocarcinoma tissues. The CDH17-high/CDX2-high pattern was predominantly expressed in small intestinal cancer tissues (75%), whereas the CDH17-low/CDX2-low pattern was observed in pancreatic cancers (63.8%) and bile duct cancers (20.9%). The study concluded that CDH17-high/CDX2-high adenocarcinomas more likely originated from small intestine versus pancreas or bile duct, whereas CDH17-low/CDX2-low ones are more likely of pancreatic origin. The combined use of CDH17 and CDX2 could be helpful in providing support for the histologic origin of periampullary adenocarcinoma.

Neoplasia-Associated Wasting Diseases with Economic Relevance in the Sheep Industry

Simple SummaryNeoplasia is a common cause of weight loss and emaciation. Despite its relative infrequency in sheep, there are three neoplastic diseases with special relevance. Small intestinal adenocarcinoma (SIA), ovine pulmonary adenocarcinoma (OPA) and enzootic nasal adenocarcinoma (ENA) are three neoplastic diseases with economic impact in the sheep industry. They mostly occur at ages under common production cycles, have epidemiological relevance in sheep rearing countries, and two of them (OPA and ENA) have an infectious aetiology. SIA occurs elsewhere in the world but has a special economic impact in Australia and New Zealand. OPA and ENA have relevant economic significance in most continents but have not been recorded in Australia and New Zealand. In this review, we focus on the epidemiology, clinicopathological features, pathogenesis and the diagnostic tools currently available for the diagnosis of these three neoplastic diseases.We review three neoplastic wasting diseases affecting sheep generally recorded under common production cycles and with epidemiological and economic relevance in sheep-rearing countries: small intestinal adenocarcinoma (SIA), ovine pulmonary adenocarcinoma (OPA) and enzootic nasal adenocarcinoma (ENA). SIA is prevalent in Australia and New Zealand but present elsewhere in the world. This neoplasia is a tubular or signet-ring adenocarcinoma mainly located in the middle or distal term of the small intestine. Predisposing factors and aetiology are not known, but genetic factors or environmental carcinogens may be involved. OPA is a contagious lung cancer caused by jaagsiekte sheep retrovirus (JSRV) and has been reported in most sheep-rearing countries, resulting in significant economic losses. The disease is clinically characterized by a chronic respiratory process as a consequence of the development of lung adenocarcinoma. Diagnosis is based on the detection of JSRV in the tumour lesion by immunohistochemistry and PCR. In vivo diagnosis may be difficult, mainly in preclinical cases. ENA is a neoplasia of glands of the nasal mucosa and is associated with enzootic nasal tumour virus 1 (ENTV-1), which is similar to JSRV. ENA enzootically occurs in many countries of the world with the exception of Australia and New Zealand. The pathology associated with this neoplasia corresponds with a space occupying lesion histologically characterized as a low-grade adenocarcinoma. The combination of PCR and immunohistochemistry for diagnosis is advised.

Small Intestinal Adenocarcinoma in a Patient With Celiac Disease

Celiac disease (CD) is a systemic immune-mediated disorder against gluten, leading to an autoantibody response causing damage to the small intestinal mucosa. CD has been associated with gastrointestinal malignancies, most commonly gastrointestinal lymphoma. Rare malignancies have also been reported, such as small intestinal adenocarcinoma. In this report, we present a case of a 91-year-old male with a history of CD, noncompliant with a gluten-free diet, who presented with weight loss, abdominal pain, and gastrointestinal bleeding secondary to a newly discovered adenocarcinoma of the jejunum.

Tumor Microenvironmental Prognostic Risk in Primary Operable Small Intestinal Adenocarcinoma.

The tumor microenvironment (TME) has become an important area of investigation with respect to improving prognosis in malignancies. Here we evaluated TME prognostic risk in small intestinal adenocarcinomas based on histologic assessment of tumor budding at the peritumoral-invasive front (pTB) and stromal tumor-infiltrating lymphocytes (sTILs). pTB and sTILs were analyzed in 230 surgically resected small intestinal adenocarcinomas, as recommended by the International Tumor Budding Consensus Conference (ITBCC) and the International TILs Working Group (ITWG). On the basis of high levels of pTB count (≥10) and sTIL density (≥20%), we combined pTB and sTIL to produce a collective TME-based prognostic risk index: low-risk (pTBLow/sTILHigh; n=39, 17.0%), intermediate-risk (pTBLow/sTILLow or pTBHigh/sTILHigh; n=99, 43.0%), and high-risk groups (pTBHigh/sTILLow; n=92, 40.0%). TME risk index provided better prognostic stratification than the individual pTB and sTIL (14.9 vs. 6.7 vs. 10.3). Tumors with higher TME prognostic risk were associated with an infiltrative growth pattern and nonintestinal immunophenotype (both P=0.001), pancreatic invasion (P=0.010), lymphovascular (P<0.001) or perineural invasion (P=0.006), higher T-category (P<0.001), N-category (P=0.004), and stage grouping (P=0.002), and KRAS mutation (P=0.008). In multivariate analysis, higher TME prognostic risk index (P<0.001), distal tumor location and nonintestinal immunophenotype (both P=0.001), higher N-category (P<0.001), and microsatellite stable (P=0.015) were worse-independent prognosticators. TME prognostic risk index consistently stratified patient survival regardless of tumor location (P<0.001 in proximal; P=0.002 in distal), stages (P<0.001 in lower stages I to II; P=0.028 in stage III), and DNA mismatch repair gene status (P<0.001 in microsatellite stable; P=0.001 in microsatellite instability). TME risk index is a powerful prognostic predictor for risk stratification of patients with small intestinal adenocarcinoma.

The role of multidetector computed tomography enterography in the evaluation of localized malignant small intestinal lesions: retrospective radiological and pathological experience.

PurposeOur purpose is to present our experience in using multidetector computed tomography (MDCT) enterography in the evaluation of localized malignant small intestinal lesions with pathological correlation.Material and methodsWe retrospectively evaluated 53 patients of pathologically proven malignant localized small intestinal tumours, who underwent multidetector CT enterography.ResultsIn this study, the mean age was 51.39 ± 17.4 years. The most commonly affected age group was from 50 to 59 years. The commonest clinical complaint was abdominal pain. The ileum was the most commonly affected anatomical region, showing 25 lesions (47.16%). Radiologically irregular/asymmetric wall thickening was detected in 42 cases(79.24%). Pathologically the most common malignancy was small intestinal adenocarcinoma, followed by carcinoid tumour, lymphoma, and gastrointestinal stromal tumours (GIST). We found that there was a statistically significant association between the pathological lymphadenopathy (p = 0.005) and absent proximal intestinal dilatation (p = 0.01) with intestinal lymphoma. Also, there was a statistically significant association between the extra-intestinal mesenteric fat changes with carcinoid tumours (p = 0.001). Irregular/asymmetric wall thickening was detected in 14 cases of small intestinal adenocarcinoma with a statistically significant association (p = 0.001) while exophytic pathological mass formation was statistically significant associated (p ≤ 0.001) with small intestinal GIST.ConclusionsMultidetector CT enterography is a non-invasive and accurate method in the evaluation of focal and localized small intestinal malignant lesions. The accurate detection of these lesions depends to some degree on the experience of the radiologist, lesional size, site and pattern of enhancement, as well as adequate intestinal distension.

Prognostic implication of SOX2 expression in small intestinal adenocarcinoma.

The presence of KRAS mutation enhances the stem cell features of colorectal carcinoma cells containing mutant adenomatous polyposis coli (APC). However, their potential role in small intestinal adenocarcinoma remains elusive. Here, we aimed to investigate the clinical significance of cancer stem cell markersexpression in the context of small intestinal adenocarcinoma with the KRAS genotype. SOX2, NANOG, and OCT4 expression were assessed by immunohistochemistry and digital image analysis, and their potential association with KRAS was further examined in 185 Korean patients with small intestinal adenocarcinomas, which were collected from 22 institutions in South Korea. Positive expression of SOX2, NANOG, and OCT4 was detected in 65 (35.1%), 94 (50.8%), and 82 (44.3%) of patients, respectively. Patients with high SOX2 (SOX2+) expression displayed worse overall survival compared to those with low SOX2 (SOX2-) expression(P < 0.001). Patients with SOX2+/mutant KRAS (KRASMT) (11.1 months) had significantly shorter overall survival than those with SOX2-/KRASWT (53.6 months) (P < 0.001). In multivariate analysis, SOX2+, distal location, high pT andpN categories, microsatellite stable, and absence of predisposing diseases were independent prognostic factors for worse overall survival. These results suggest that SOX2 expression has the potential to predict clinical outcomes in patients with small intestinal adenocarcinomas.

Reply to Comment on "Jun, S.Y.; et al. Tumor Budding and Poorly Differentiated Clusters in Small Intestinal Adenocarcinoma" Cancers 2020, 12, 2199.

We thank Giuffrida et al [...].

Comment on Jun, S.Y.; et al. "Tumor Budding and Poorly Differentiated Clusters in Small Intestinal Adenocarcinoma" Cancers 2020, 12, 2199.

We read with interest the paper by Jun S [...].