Materiały źródłowe

• #1 Small Bowel Cancer – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560725/

  Small bowel cancer encompasses a series of malignant lesions that may be identified throughout the small intestine (SI). […] While both benign and malignant lesions can be identified throughout the SI, the overall incidence of small bowel neoplasms is extremely low compared to lesions noted in other portions of the gastrointestinal tract. […] The majority of these lesions cause multiple nonspecific symptoms, which often leads to delay in diagnosis and therefore delay in early intervention with available treatment strategies. […] Diagnosis can be variable based on the location of the lesion under investigation and generally consists of laboratory studies, radiographic imaging, and endoscopic evaluation. […] Two well-studied small intestine malignancies considering their molecular pathogenesis are adenocarcinomas and GISTs. However, less significant progress has been reported in exploring the pathogenesis of the other small-intestinal tumors.

• #2 Small Bowel: Malignant Tumors Imaging Pearls – Educational Tools | CT Scanning | CT Imaging | CT Scan Protocols – CTisus

  https://www.ctisus.com/learning/pearls/small-bowel/malignant-tumors

  Small bowel adenocarcinomas make up about approximately 31% to 40% of small bowel malignancies. These primary adenocarcinomas, arising from the glandular epithelium, are most common in the duodenum (60%), followed by the jejunum (25%29%), and ileum (10%13%). Patients often present with nonspecific symptoms, leading to delayed diagnoses and many patients present emergently due to obstruction or bleeding from advanced disease. Most cases are sporadic, but associations with polyposis syndromes and inflammatory bowel diseases like Crohns or celiac disease exist. […] Small bowel cancers are very rare despite the length and large mucosal surface of the small bowel and account for 3% to 6% of all gastrointestinal (GI) tract malignancies. Adenocarcinoma, neuroendocrine neoplasms, lymphoma, and GI stromal tumors (GISTs) are the most prevalent primary small bowel cancers, with adenocarcinoma and neuroendocrine neoplasms accounting for nearly two-thirds of small bowel cancers.

• #3 Small Bowel Cancer – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/sites/books/NBK560725/

  Small bowel cancer encompasses a series of malignant lesions that may be identified throughout the small intestine (SI). […] The majority of these lesions cause multiple nonspecific symptoms, which often leads to delay in diagnosis and therefore delay in early intervention with available treatment strategies. […] Two well-studied small intestine malignancies considering their molecular pathogenesis are adenocarcinomas and GISTs. However, less significant progress has been reported in exploring the pathogenesis of the other small-intestinal tumors. A similar pathogenesis background to colorectal adenocarcinoma with sequential genetic aberrancies has been attributed to small intestine adenocarcinoma. […] The basis for each malignancy is dependent on genetics and mutations that occur, resulting in malignant transformation of the cells.

• #4 Small Bowel Cancer – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560725/

  The basis for each malignancy is dependent on genetics and mutations that occur, resulting in malignant transformation of the cells. […] The five main types and cells of origin include: […] A similar pathogenesis background to colorectal adenocarcinoma with sequential genetic aberrancies has been attributed to small intestine adenocarcinoma. […] Pathological sequences of GIST tumors, including mutations with a gain of function tendency of proto-oncogene KIT, with a key role in unopposed cellular growth, have been well identified.

• #5 Small Bowel Cancer – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/sites/books/NBK560725/

  The five main types and cells of origin include: Sarcoma – is generally classified as leiomyosarcoma and primarily arises from muscle tissue; and it is most commonly found in the ileum but can be found throughout the SI. […] GIST or gastrointestinal stromal tumors are thought to arise from the interstitial cells of Cajal. These particular tumors are considered soft tissue sarcomas. […] Adenocarcinoma – usually develops through the malignant transformation of glandular cells of the SI. […] Neuroendocrine tumors – Also known as carcinoid tumors and are generally derived from hormone-producing cells and therefore are generally associated with secretory cells that cause particular clinical features. […] Lymphoma – derived from the lymphatics associated with the small intestine. […] The interstitial cells of Cajal have an integral role in the GISTs tumor, and the specific staining for CD117 antigen, the KIT receptor, is present in most GIST tumors.

• #6 Small intestine cancer pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Small_intestine_cancer_pathophysiology

  Small intestinal cancers is a rare condition and information on its pathophysiologic mechanisms is limited. […] Pathophysiology of small intestinal cancers depends on the histological subtype. […] Low susceptibility of the small intestine to malignant changes may be explained as follows: Short exposure of the mucosa to carcinogens due to rapid transit of contents, Liquid nature of the contents and less mucosal irritation, Low bacterial load, High concentration of lymphoid tissue. […] Adenocarcinoma of small intestine is more common in patients with colorectal cancer, suggesting a common pathogenetic mechanism. […] Development of adenocarcinoma in duodenum may be explained by vigorous exposure of that part of intestine to different carcinogens, which gets diluted in the latter part of intestine.

• #7 Current Advance in Small Bowel Tumors

  https://www.e-ce.org/journal/view.php?number=6345

  Small intestinal tumors are difficult challenge to gastroenterologists. […] The most frequent neoplasms are adenomas and mesenchymal tumors. […] Multiple factors influence on the relative infrequency of tumorigenesis in the small bowel; rapid small bowel (SB) transit time, a high concentration of the enzyme detoxifying carcinogen, abundant lymphoid tissue and high levels of IgA, alkaline pH and the lower bacterial load, and rapid turnover of the intestinal mucosa. […] Genetically predisposing conditions such as familial adenomatous polyposis (FAP), hereditary non-polyposis colorectal cancer (HNPCC), celiac disease, and Peutz-Jeghers syndrome (PJS) are associated with increased incidence of the small intestinal adenocarcinoma. […] Acquired conditions including biliary diversion, ileostomy stomas, pouches, and conduits increase the risk of small bowel adenocarcinoma.

• #8

  https://journals.lww.com/ajg/abstract/2005/03000/pathogenesis_and_risk_factors_of_small_bowel.30.aspx

  Small bowel adenocarcinoma (SBA) is a very rare entity accounting for one-fourth of the small intestine neoplasms. […] It appears that SBA shares several genetic characteristics with large bowel tumors, but also has unique features. […] The purpose of this article is to review pathogenesis and risks factors of SBA to better understand its molecular features as well as its resemblances and dissimilarities with colorectal cancer (CRC). […] Better understanding of sporadic and hereditary genetic pathways potentially involved will undoubtedly lead to better prevention and therapeutic management of this rare but aggressive disease.

• #9 Small bowel adenocarcinoma: An overview

  https://www.wjgnet.com/1948-5204/full/v14/i2/413.htm

  Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract. However, these tumors are among those with worst prognosis. […] Currently, there is not enough information on the molecular characteristics and tumor pathogenesis. […] In contrast to CRC, studies evaluating the pathogenesis of SBA are lacking due to the rarity of the disease. […] However, the probable hypotheses include rapid turnover of small intestinal epithelium due to accumulated genetic damage and increased lymphoid tissue allowing increased immune surveillance. […] Most of the cases of SBA are sporadic, but an increased risk is seen in inherited cancer syndromes, like Lynch syndrome, familial adenomatous polyposis, and Peutz-Jeghers syndrome. […] A study found that DNA copy number aberrations seen in SBA are more similar to CRCs than to gastric cancer.

• #10 Small intestine cancer pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Small_intestine_cancer_pathophysiology

  Adenoma-carcinoma sequence is hypothesized to play the role in development of small intestine adenocarcinoma; however, no studies confirms the theory. […] Stromal tumors of small intestine may be associated with activating mutations in the KIT or platelet-derived growth factor receptor alpha (PDGFRA) genes.

• #11 Small intestine cancer – Wikipedia

  https://en.wikipedia.org/wiki/Small_intestine_cancer

  Small intestine cancer is a cancer of the small intestine. It is relatively rare compared to other gastrointestinal malignancies such as gastric cancer (stomach cancer) and colorectal cancer. […] Experts believe that small intestine cancer develops much like colorectal cancer. It first begins as a small growth on the inner lining of the intestine (polyp), which over time becomes cancer. […] Approximately 50% of adenomas of the small intestine arise in the duodenum even though this location comprises only 4% of the length of the small intestine. These adenomas occur mainly close to the ampulla of Vater, the outlet of the common bile duct from which bile acids are released. […] Most small intestine cancers (especially adenocarcinomas) develop in the duodenum. Cancers developed in the duodenum are often found at the ampulla of Vater.

• #12

  https://link.springer.com/article/10.1007/s10439-023-03155-8

  Bowel cancer is a multifactorial disease arising from a combination of genetic predisposition and environmental factors. […] In this review, we summarised the origin of bowel cancer and the mechanism of its metastasis. […] The adenoma-carcinoma sequence was reported in 1980, elucidating the metamorphosis of normal colorectal epithelium to adenoma, and then to invasive and metastatic tumours. […] The accumulation of acquired genetic and epigenetic alterations that turn normal glandular epithelial cells into invasive adenocarcinomas is a critical element of bowel cancer development. […] The polyp-to-cancer progression sequence, also known as the adenoma-carcinoma sequence, was postulated in Vogelstein and Fearons pioneering and classic tumour development model. […] It connects genetic alterations to the order in which tumour morphology alters at different stages of cancer development, beginning with a step that promotes the formation of benign neoplasms (e.g. adenomas and sessile serrated polyps), then a step that promotes the progression to more histologically advanced neoplasms, and finally a step that transforms the tumours to invasive carcinoma.

• #13 Small Bowel Tumours – TeachMeSurgery

  https://teachmesurgery.com/general/small-bowel/small-bowel-tumours/

  Small bowel adenocarcinomas are believed to arise from pre-existing adenomas through a sequential accumulation of genetic abnormalities (a model similar to that described for the pathogenesis of colorectal cancer), which can occur over several years. […] The tumour suppressor gene p53, which maintains DNA integrity, and the oncogene KRAS, which normally functions in cellular signalling and proliferation, have been implicated in over 50% of small bowel adenocarcinoma cases.

• #14 Small bowel adenocarcinoma: An overview

  https://www.wjgnet.com/1948-5204/full/v14/i2/413.htm

  The common carcinogenesis pathway involved in both SBA and CRC include KRAS mutations, loss of 18q and p53, and relatively lower rates of APC mutations. […] Recently, a comprehensive genomic analysis of SBA demonstrated that it is a molecularly unique cancer. […] The frequency of genetic mutations in SBA is significantly different from that in CRC (APC: 27% vs 76%, CDKN2A: 14.5% vs 2.6%) or gastric carcinoma (KRAS: 53.6% vs 14.2%, SMAD4: 17.4% vs 5.2%). […] IHC of the pathways of tumorigenesis reveals that the pathogenesis of SBA and CRC are significantly different.

• #15 Molecular Landscape of Small Bowel Adenocarcinoma

  https://www.mdpi.com/2072-6694/14/5/1287

  Genomic profiling studies have identified a number of critical molecular drivers in the pathogenesis of SBA, including E-cadherin, KRAS, TP53, and SMAD4, among others. […] SBA has also been associated with a higher likelihood of microsatellite instability (MSI) and high tumor mutational burden (TMB). […] Perhaps the finding of greatest clinical relevance through comprehensive genomic analyses is that over 90% of SBAs harbor targetable genetic alterations. […] Activation of the WNT pathway through accumulation of beta-catenin may have a role in a subset of SBAs, but this accumulation appears much less frequently caused by inactivating APC gene mutations when compared to CRC.

• #16 Exome-wide somatic mutation characterization of small bowel adenocarcinoma | PLOS Genetics

  https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007200

  The most commonly mutated genes in SBA include TP53, KRAS, SMAD4, and APC. […] The assessment of relevant genes in SBA indicated that TP53 and KRAS were the most significantly mutated genes in MSS tumors, the mutation frequencies corresponding to previous reports. […] APC reached an equally high level of significance with TP53 and KRAS in the analysis of MSS tumors. […] Among the most significantly mutated genes was also BRAF, a well-known oncogene mutated in various cancers, such as melanoma (44%), CRC (10%), and lung adenocarcinoma (10%). […] Exome data analysis also revealed other significantly mutated genes previously linked to SBA (e.g. SMAD4), recently reported potential driver genes (e.g. SOX9, ATM, and ARID2), and novel candidates (e.g. ACVR2A, ACVR1B, BRCA2, and SMARCA4) that have not previously been linked to SBA. […] The results presented here provide further evidence that SBA is a genetically distinct tumor entity.

• #16 Exome-wide somatic mutation characterization of small bowel adenocarcinoma | PLOS Genetics

  https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007200

  Small bowel adenocarcinoma (SBA) is an aggressive disease with limited treatment options. […] To comprehensively characterize the mutational landscape of this tumor type, and to identify possible targets of treatment, we conducted the first large exome sequencing study on a population-based set of SBA samples from all three small bowel segments. […] Exome data analysis revealed significantly mutated genes previously linked to SBA (TP53, KRAS, APC, SMAD4, and BRAF), recently reported potential driver genes (SOX9, ATM, and ARID2), as well as novel candidate driver genes, such as ACVR2A, ACVR1B, BRCA2, and SMARCA4. […] SBAs are often sporadic, however, several factors such as inflammatory bowel disease (IBD; Crohn’s disease and ulcerative colitis) and hereditary syndromes such as familial adenomatous polyposis (FAP) and Lynch syndrome (LS) are known to predispose to these tumors.

• #17 Potential biomarkers and immune characteristics of small bowel adenocarcinoma | Scientific Reports

  https://www.nature.com/articles/s41598-022-20599-5

  Small bowel adenocarcinoma (SBA) is a gastrointestinal malignancy with low incidence but poor prognosis, and its pathogenesis is still unclear. […] Currently, the understanding of the pathogenesis of SBA is still limited. The traditional concept is that the pathogenesis of SBA is similar to that of colon cancer but lacks exact evidence. Several key molecular drivers in the pathogenesis of SBA have been identified by genomic profiling studies, including TP53, SMAD4, KRAS and E-cadherin. […] Four target genes (APOA4, APOB, COL1A2, FN1) may be involved in the pathogenesis of small bowel adenocarcinoma. […] In this study, four hub genes (APOA4, APOB, COL1A2, FN1) were found to be significantly related to the pathogenesis of SBA. […] This study suggests that the highly expressed FN1 plays an important role in the carcinogenesis of SBA. […] In addition, the low infiltration of most immune cells and the weak activation of immune pathways may be important factors for the occurrence and progression of SBA.

• #18

  https://link.springer.com/article/10.1007/s10439-023-03155-8

  The microsatellite instability pathway is characterised by a clonal increase in the number of repeated DNA nucleotide units in microsatellites, resulting from the inactivation of mismatch repair (MMR) genes. […] The pathway of CpG island methylator phenotype is described by the global hypermethylation of promoter CpG island sites, which also results in the inactivation of tumour suppressor genes. […] Interestingly, bowel cancers that occur on the left side (descending colon, sigmoid colon and rectum) and right side (transverse colon, ascending colon and caecum) have different biological and clinical characteristics. […] Epidemiological and cross-sectional studies led to the proposal that the gut microbiome is closely associated with the development of bowel cancer. […] The intestinal bacterial flora that make up this microbiome achieve carcinogenic effects by destroying the homeostasis of the microenvironment, changing the immune response and the biofilm of intestinal bacteria, and producing toxic metabolites.

• #19 Colorectal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Colorectal_cancer

  Mismatch repair (MMR) deficient tumours are characterized by a relatively high number of poly-nucleotide tandem repeats. This is caused by a deficiency in MMR proteins which are typically caused by epigenetic silencing and or inherited mutations (e.g., Lynch syndrome). 15 to 18 percent of colorectal cancer tumours have MMR deficiencies, with 3 percent developing due to Lynch syndrome. The role of the mismatch repair system is to protect the integrity of the genetic material within cells (i.e., error detecting and correcting). Consequently, a deficiency in MMR proteins may lead to an inability to detect and repair genetic damage, allowing for further cancer-causing mutations to occur and colorectal cancer to progress. […] The polyp to cancer progression sequence is the classical model of colorectal cancer pathogenesis. In this adenoma-carcinoma sequence, normal epithelial cells progress to dysplastic cells such as adenomas, and then to carcinoma, by a process of progressive genetic mutation. Central to the polyp to CRC sequence are gene mutations, epigenetic alterations, and local inflammatory changes. The polyp to CRC sequence can be used as an underlying framework to illustrate how specific molecular changes lead to various cancer subtypes.

• #20 Small-Intestine Cancer, IBD, and the Role of Gut Dysbiosis

  https://www.uspharmacist.com/article/smallintestine-cancer-ibd-and-the-role-of–gut-dysbiosis

  While little is known about their etiology, it has been observed that cancers of the small intestine are more common in individuals with a number of inflammatory bowel diseases (IBDs) and other conditions. […] It is now accepted that the microbiome is a significant, multifaceted key player in the development of inflammation. […] IBD is a result of chronic inflammation caused, in some part, by dysbiosis of intestinal microbiota; this mainly occurs with commensal bacteria those that derive benefit without harming or benefiting the host. […] It has been suggested that dysbiosis is the result of gut microbiota interacting with genetic contributions (risk loci), which subsequently leads to the development of IBD. […] In addition to the possibility of dysbiosis, bacterial factors are now thought to interact with the immune system in order for inflammation to occur. […] The role of the pharmacist in antibiotic stewardship regarding the use of broad spectrum ABT is supported, particularly in light of evidence for a role for microbiota therapies and dietary interventions as effective ways to modulate gut microbiota.

• #21 Small Bowel: Malignant Tumors Imaging Pearls – Educational Tools | CT Scanning | CT Imaging | CT Scan Protocols – CTisus

  https://www.ctisus.com/learning/pearls/small-bowel/malignant-tumors

  T-cell lymphoma, which occurs much less frequently than B-cell lymphoma, tends to develop in the proximal portion of the small bowel, such as the jejunum or proximal ileum. Perforation is observed in 1633% of patients with T-cell lymphoma at the time of clinical presentation, and this is attributed to transmural involvement and necrosis. Additionally, T-cell lymphoma is more likely to be multifocal disease than is B-cell lymphoma. […] The relative risk of developing small bowel adenocarcinoma in Crohns disease is about 20. In Crohns disease, the preferred location is the ileum and the age at onset is younger (4th decade). If there is a family history of Crohns disease or if there are clinical symptoms, a morphological examination of the small bowel and a proctologic examination are recommended.

• #22 Celiac Disease and Small Bowel Cancers: A Question of Risk – Gastroenterology Advisor

  https://www.gastroenterologyadvisor.com/news/celiac-disease-and-small-bowel-cancers-a-question-of-risk/

  Despite many studies showing a potential association between CD and small bowel cancer, there is a lack of data evaluating the risk of specific subtypes of small bowel cancer, such as lymphomas, adenocarcinomas, carcinoids, and sarcomas. […] The HR for small bowel adenocarcinoma was 3.05 (95% CI, 1.86-4.99). […] The HR of small bowel adenocarcinoma was higher for those located in the jejunum and ileum (HR 3.92; 95% CI, 1.80-8.56) compared with those located in the duodenum (HR 2.69; 95% CI, 1.46-4.96). […] Although there was an increased risk compared with the general population, the study authors did not recommend routine screening based on the low absolute risk. […] Despite the lack of statistical significance between mucosal healing and small bowel adenocarcinoma risk, the study authors still believe that improved healing may lead to decreased risk of small bowel cancer over time. […] Several studies have found that CD may lead to increased risk of mortality and may be linked to the degree of inflammation seen on small bowel biopsies. […] Gastroenterologists will continue to struggle with how to best prevent and diagnose small bowel cancer in their patients with CD.

• #23 Molecular Landscape of Small Bowel Adenocarcinoma

  https://www.mdpi.com/2072-6694/14/5/1287

  Small bowel adenocarcinoma (SBA) is a rare malignancy with worse prognosis compared to other cancers of the gastrointestinal tract. Over 90% of SBA tumors harbor targetable genetic alterations. Molecular analysis to identify these alterations, using tissue- or blood-based next generation sequencing, is critical and may impact treatment decisions. The aim of our review is to highlight molecular drivers of SBA tumorigenesis. […] The etiology of SBA remains largely unknown. Small retrospective analyses have identified cigarette smoking and alcohol as potential environmental risk factors; other studies have suggested an association between high sugar or high red meat intake and the development of SBA. […] Recent advances in genomic profiling have highlighted key differences between these tumors, establishing SBA as a molecularly unique intestinal cancer. Moreover, comprehensive molecular analysis has identified a relatively high incidence of potentially targetable genomic alterations in SBA, predictive of response to targeted and immunotherapies.

• #24 Clinicopathological Features and Prognostic Factors in Patients with Small Bowel Adenocarcinoma – Bagcilar Medical Bulletin

  https://www.behmedicalbulletin.org/articles/clinicopathological-features-and-prognostic-factors-in-patients-with-small-bowel-adenocarcinoma/doi/BMB.galenos.2022.2022-02-015

  Small bowel adenocarcinoma is a rare tumor, and data on prognosis are limited. […] Several theories have been proposed to explain the rarity of small bowel tumors. […] It has been stated that alcohol consumption, smoking, dietary characteristics, and Celiac disease pose a risk for the development of small bowel cancer. […] Patients with SBA have a poor prognosis. […] Due to delays in diagnosis, most of the patients present in the metastatic stage. […] In our study, patients over the age of 60 years were found to have a higher risk in terms of OS than those younger than 60 years. […] In addition, patients who did not undergo surgery (primary or palliative) at the time of diagnosis were found to have a poor prognosis. […] To diagnose and treat SBA more effectively, multicenter randomized controlled studies with large numbers of patients are needed in the future.

• #25 Small intestine cancer – Wikipedia

  https://en.wikipedia.org/wiki/Small_intestine_cancer

  Risk factors for small intestine cancer include age, race, HIV/AIDS, sex, diet, Crohn’s disease, celiac disease, radiation exposure, hereditary gastrointestinal cancer syndromes, and cholecystectomy, which alters the flow of bile to the small intestine, increases the risk of small intestinal adenocarcinomas, and this risk declines with increasing distance from the common bile duct. […] Pathogenesis and risk factors of small bowel adenocarcinoma: a colorectal cancer sibling?

• #26 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20200618/Study-identifies-a-previously-unknown-mechanism-that-contribute-to-intestinal-cancer.aspx

  A MedUni Vienna study group has identified a previously unknown mechanism involved in the development of intestinal cancer: The bacterial microbiome activates the so-called immune checkpoint Ido1 in Paneth cells, a special cell that is only found in the gastrointestinal tract, thereby preventing local intestinal inflammation. […] However, this also gives rise to immunosuppressed areas, in which intestinal tumours can develop. […] The researchers knocked-out the transcription factor Stat1 in intestinal epithelial cells of so-called ApcMin mice, which develop intestinal tumours due to a mutation in the Apc gene. […] The result was that they developed smaller and less aggressive tumours. Moreover, these tumours were infiltrated by immune cells that play a role in tumour defence. […] Ido1 encodes an enzyme that produces the metabolite kynurenine. Kynurenine suppresses the immune response in the tumour, thereby promoting tumour growth.

• #27 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20200618/Study-identifies-a-previously-unknown-mechanism-that-contribute-to-intestinal-cancer.aspx

  Further studies have shown that ApcMin tumours with an intact Stat1 gene contain special cells that express Ido1. […] Ido1 expression in the Paneth cells is stimulated by interaction with the bacterial microbiome. […] According to our hypothesis, the bacterial microbiome induces the Ido1 immune checkpoint in the Paneth cells, thereby preventing local intestinal inflammation. However, this also gives rise to immunosuppressed areas, in which intestinal tumours can develop. Ido1-expressing Paneth cells are therefore a cellular target for immune-based therapies.

• #28

  https://link.springer.com/article/10.1007/s10439-023-03155-8

  In addition to the above carcinogenic mechanisms, transcription factors are also the main driving factors for colorectal tumours. […] The risk of developing bowel cancer is also clearly associated with exogenous factors, such as lifestyle, environmental and socioeconomic factors. […] Thus, a combination of acquired genetic mutations due to environmental exposure to carcinogens and, in some, inherited genetic predisposition appears to provoke the development of adenomas and cancers. […] Cancer metastasis is the process whereby primary tumour cells spread from the original tumour site and establish secondary tumour colonies in distant organs. […] The most common site of metastasis from bowel cancer is the liver, and this is often the only site where metastasis is observed. […] Once a primary bowel tumour reaches a volume of approximately 2 mm3, it relies on the formation of new vascular networks to provide a suitable supply of nutrients and oxygen and facilitate the removal of waste.

• #29

  https://link.springer.com/article/10.1007/s10439-023-03155-8

  The processes in which new blood and lymphatic vessels form is called angiogenesis and lymphangiogenesis, respectively. […] To gain access to the blood stream, cancer cells must first detach from the tumour and invade through the extracellular matrix or infiltrate local tissue. […] Epithelial mesenchymal transition is the process in which tumour associated epithelial cells change phenotype and transform to acquire more invasive and metastatic mesenchymal cell properties. […] The tumour microenvironment is made up of inflammatory and immune cells, including cancer associated fibroblasts, neutrophils and macrophages, and environmental conditions, such as signalling molecules and the extracellular membrane. […] Local invasion of the tumour cells starts with the degradation of the basement membrane, followed by the migration of tumour cells through the surrounding stroma towards nearby tissue or neighbouring blood and lymphatic vessels, highly facilitated by angiogenesis.

• #30

  https://link.springer.com/article/10.1007/s10439-023-03155-8

  When primary tumour cells successfully migrate into the blood stream through intravasation, they become circulating tumour cells (CTCs) and are considered as one of the main biomarkers for metastatic spread. […] For the tumour cells to successfully proliferate and start secondary tumours in distant sites, CTCs must first exit the blood stream via the process of extravasation. […] The entire cycle of bowel cancer metastasis is graphically presented in Fig. 3.

• #31 Pathobiological Implications of Mucin (MUC) Expression in the Outcome of Small Bowel Cancer | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0086111

  Mucins have been associated with survival in various cancer patients, but there have been no studies of mucins in small bowel carcinoma (SBC). In this study, we investigated the relationships between mucin expression and clinicopathologic factors in 60 SBC cases, in which expression profiles of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC6 and MUC16 in cancer and normal tissues were examined by immunohistochemistry. MUC1, MUC5AC and MUC16 expression was increased in SBC lesions compared to the normal epithelium, and expression of these mucins was related to clinicopathologic factors, as follows: MUC1 [tumor location (p=0.019), depth (p=0.017) and curability (p=0.007)], MUC5AC [tumor location (p=0.063) and lymph node metastasis (p=0.059)], and MUC16 [venous invasion (p=0.016) and curability (p=0.016)]. Analysis of 58 cases with survival data revealed five factors associated with a poor prognosis: poorly-differentiated or neuroendocrine histological type (p0.001), lymph node metastasis (p0.001), lymphatic invasion (p=0.026), venous invasion (p0.001) and curative resection (p0.001), in addition to expression of MUC1 (p=0.042), MUC5AC (p=0.007) and MUC16 (p0.001). In subsequent multivariate analysis with curability as the covariate, lymph node metastasis, venous invasion, and MUC5AC and/or MUC16 expression were significantly related to the prognosis. Multivariate analysis in curative cases (n=45) showed that SBC with MUC5AC and/or MUC16 expression had a significantly independent high hazard risk after adjusting for the effects of venous invasion (hazard ratio: 5.6, 95% confidence interval: 1.817). In conclusion, the study shows that a MUC5AC-positive and/or MUC16-positive status is useful as a predictor of a poor outcome in patients with SBC.

• #32 Pathobiological Implications of Mucin (MUC) Expression in the Outcome of Small Bowel Cancer | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0086111

  Small bowel carcinoma (SBC) is a rare malignancy, in contrast to colorectal carcinoma. A surgical approach is mainly used to treat SBC, but many patients have a poor outcome after curative resection. Lymph node metastasis, distant metastasis, primary tumor status and tumor differentiation have been reported as prognostic factors in SBC. […] To date, only two articles have discussed mucins in SBC and the clinical significance of mucin expression in SBC is unknown. Therefore, the aim of the present study was to investigate whether expression of mucins (MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC6 and MUC16) has prognostic significance in patients with SBC using specimens obtained from surgical departments at multiple hospitals. […] MUC1, MUC5AC and MUC16 showed increased expression; MUC4 and MUC6 showed equal expression; and MUC2 and MUC3 showed decreased expression in SBC compared to normal epithelium.

• #33 Pathobiological Implications of Mucin (MUC) Expression in the Outcome of Small Bowel Cancer | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0086111

  MUC1 expression was related to tumor location (high for oral side, p=0.019), invasion depth (higher for deeper than pSS (pT3), p=0.017), venous invasion (high for positive venous invasion, p=0.038), and curability (high for non-curative resection, p=0.007). MUC2 expression was related to tumor location (high for anal side, p=0.034), negative lymphatic invasion (p=0.041) and histological type (high for mucinous carcinoma, p=0.005). MUC5AC expression was marginally related to tumor location (p=0.063) and lymph node metastasis (p=0.059). MUC16 expression was related to venous invasion (high for positive venous invasion, p=0.016) and curability (high for non-curative resection, p=0.016). […] The expression of MUC1, MUC5AC and MUC16 were poorer than those of patients without expression of MUC1 (p=0.042), MUC5AC (p=0.007) and MUC16 (p0.001), respectively. […] The results of this study demonstrate that a MUC5AC-positive and/or MUC16-positive mucin expression pattern is a useful marker to predict a poor outcome in patients with SBC.

• #34 Current Advance in Small Bowel Tumors

  https://www.e-ce.org/journal/view.php?number=6345

  The diagnostic processes directed by the clinical presentation often start from the simplest examination modalities and findings are often vague and inconclusive. […] On the bases of known risk factors for small intestinal malignant tumors, patients at risk might have benefit from proper surveillance. […] Early diagnosis and treatment of small intestinal adenoma/cancer in patients with HNPCC syndrome will probably improve prognosis. […] Cancers arising in the small bowel pose a unique and difficult challenge to gastroenterologists, surgeons, and hematooncologists.

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