The human papillomavirus (HPV) is an oncogenic DNA virus that is the most commonly transmitted sexually transmitted virus. There is substantial evidence that HPV is associated with different types of cancer. While the majority of studies have concentrated on urogenital system cancers and head and neck cancers, the relationship between HPV and gastrointestinal system cancers, particularly esophageal cancers, has also been the subject of investigation. Given that HPV is a disease that can be prevented through vaccination and treated with antiviral agents, identifying the types of cancers associated with the pathogen may inform the treatment of these cancers. This comprehensive review examines the relationship between HPV and cancers of the upper gastrointestinal tract, highlighting the oncogenic mechanisms of the virus and its reported prevalence. A deeper understanding of HPV's association with cancer is relevant to the further development of cancer therapies.

Small intestinal adenocarcinomas (SIAs) are associated with predisposing conditions, including inflammatory bowel disease (IBD) and celiac disease, but also genetic syndromes such as Lynch syndrome (LS) and familial adenomatous polyposis (FAP). This nationwide cohort study investigated the incidence of genetic and non-genetic predisposing conditions in SIA and their influence on tumor characteristics and clinical features. Data were obtained from the Netherlands Cancer Registry. The incidence, characteristics, and clinical features per predisposing condition were analyzed in 2697 SIA patients diagnosed from 1999 through 2019. Of all SIA patients, 5.6% were known to have a genetic predisposing syndrome, of whom 4.0% had LS and 1.6% had a polyposis syndrome. In addition, 6.8% of SIA patients had a non-genetic predisposing condition: 3.9% IBD and 2.9% celiac disease. SIAs of patients with such predisposing syndromes or conditions were diagnosed at a younger age and earlier stage and affected the duodenum less often as compared to sporadic SIA patients. Both genetic and non-genetic predisposing conditions were associated with significantly better overall survival (OS) compared to sporadic SIA: sporadic SIA (median OS: 13.0 months, 95% CI: 11.8-14.2), LS (213.1 months, 99.3-NA), polyposis syndromes (61.3 months, 19.7-NA), IBD (29.5 months, 20.3-69.8), and celiac disease (50.4 months, 24.6-124.7). This nationwide cohort study shows significant differences between SIA with and without predisposing conditions and highlights the need for research on underlying molecular mechanisms to improve outcomes of SIA patients.

Surgical resection (SR) is the main treatment for small bowel adenocarcinoma (SBA), but it increases metabolic demand, systemic inflammation, and digestive dysfunction, resulting in major impacts on the postoperative outcomes of patients. In this study, we aimed to investigate the role of the postoperative prognostic nutritional index (PNI), a surrogate marker of inflammation and nutrition, in patients with SBA after resection.

From June 2014 to March 2022, 44 consecutive patients who underwent SR for SBA in Taipei Veterans General Hospital were retrospectively reviewed. Factors associated with survival including PNI were analyzed.

PNI decreased in patients after SR for SBA (median change: -1.82), particularly in those who underwent Whipple operation or developed postoperative pancreatic fistula. Postoperative PNI <45.2 best predicted overall survival (OS) (area under the receiver operating characteristic curve [AUROC]: 0.826, p = 0.001). Patients with lower postoperative PNI had significantly worse OS compared to those with higher postoperative values (median OS: 19.3 months vs not reached, p < 0.001). Low postoperative PNI (hazard ratio [HR]: 11.404, p = 0.002), tumoral lymphovascular invasion (HR: 8.023, p = 0.012), and adjuvant chemotherapy (HR: 0.055, p = 0.002) were independent risk factors for OS. Postoperative PNI also significantly predicted recurrence-free survival independent of lymphovascular invasion and adjuvant chemotherapy (HR: 6.705, p = 0.001).

PNI commonly decreases in patients with SBA who undergo Whipple surgery or develop postoperative pancreatic fistula. Postoperative PNI independently predicts survival and may serve as a clinical marker to optimize patient outcomes.

Here we report a case of primary adenocarcinoma of the upper jejunum, for which an early diagnosis could be made by computed tomography.

Diagnosing small bowel adenocarcinomas presents challenges due to non-specific symptoms, rarity and gastroscopy and colonoscopy's limited small intestine access, highlighting targeted diagnostic procedures' necessity. We present a late-diagnosed metastatic small bowel adenocarcinoma case in a man in his 80s who had asymptomatic mild iron-deficiency anaemia 1 year before diagnosis, with no active bleeding found on endoscopies. He experienced a single rectal bleeding episode 9 months prediagnosis, with subsequent severe iron-deficiency anaemia and no clear gastrointestinal source identified on gastroscopy. For 2 months, he had intermittent postprandial diarrhoea without abdominal pain, infectious or inflammatory causes. He experienced significant weight loss over 3 months prediagnosis. Subsequent gastroscopy indicated duodenal-gastric food retropulsion, suggesting a downstream blockage. Magnetic resonance enterography showed proximal jejunum thickening. Push enteroscopy confirmed jejunum adenocarcinoma. CT scans detected liver and peritoneal metastases. After one chemotherapy cycle, his condition worsened, leading to his passing 2 months post diagnosis.

The aim of this research is to discuss the research status, hotspots, frontiers, and development trends in the field of small bowel adenocarcinoma based on bibliometrics and visual analysis by CiteSpace software.

The relevant research articles on SBA from 1923 to 2023 were retrieved from the Web of Science Core Collection database. CiteSpace software was used to form a visual knowledge map and conduct analysis for the countries/regions, journals, authors, keywords, clusters, research hotspots and frontiers of the included articles.

There were 921 articles included, and the number of articles published during 1923-2023 is increasing. The country with the highest number of articles published was the United States (443, 38.76%), followed by Japan (84, 9.12%) and France (72, 7.82%). The author with the highest number of publications is Ansell, Overman MJ (33, 3.58%), and the author with the highest co-citation frequency is Overman MJ (218). Journal of Clinical Oncology is the journal with the highest publication frequency. The top five cluster groups were "chemotherapy", "inflammatory bowel disease", "celiac disease", "tumor" and "small intestine". The related disease, chemotherapy drugs, and treatment regimens of SBA form the main research fields, and prognosis and diagnosis are the research hotspots and trends.

The global research field in SBA has expanded in the past 100 years. The prognosis and new diagnosis of SBA are hotspots in this field and require further study in the future.

Celiac disease (CD) is a gluten-sensitive immune-mediated enteropathy. This proof-of-concept study used a convolutional neural network (CNN) to classify hematoxylin and eosin (H&E) CD histological images, normal small intestine control, and non-specified duodenal inflammation (7294, 11,642, and 5966 images, respectively). The trained network classified CD with high performance (accuracy 99.7%, precision 99.6%, recall 99.3%, F1-score 99.5%, and specificity 99.8%). Interestingly, when the same network (already trained for the 3 class images), analyzed duodenal adenocarcinoma (3723 images), the new images were classified as duodenal inflammation in 63.65%, small intestine control in 34.73%, and CD in 1.61% of the cases; and when the network was retrained using the 4 histological subtypes, the performance was above 99% for CD and 97% for adenocarcinoma. Finally, the model added 13,043 images of Crohn's disease to include other inflammatory bowel diseases; a comparison between different CNN architectures was performed, and the gradient-weighted class activation mapping (Grad-CAM) technique was used to understand why the deep learning network made its classification decisions. In conclusion, the CNN-based deep neural system classified 5 diagnoses with high performance. Narrow artificial intelligence (AI) is designed to perform tasks that typically require human intelligence, but it operates within limited constraints and is task-specific.

Small bowel adenocarcinoma (SBA) is a rare gastrointestinal malignancy with an increasing incidence and a high propensity for liver metastasis (LM). This study aimed to investigate the risk factors for synchronous LM and prognostic factors in patients with LM.

Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, this study analyzed data from 2,064 patients diagnosed with SBA between 2010 and 2020. Logistic regression was used to determine risk factors for synchronous LM. A nomogram was developed to predict the risk of LM in SBA patients, and its predictive performance was assessed through receiver operating characteristic (ROC) curves and calibration curves. Kaplan-Meier and Cox regression analyses were conducted to evaluate survival outcomes for SBA patients with LM.

Synchronous LM was present in 13.4% of SBA patients (n = 276). Six independent predictive factors for LM were identified, including tumor location, T stage, N stage, surgical intervention, retrieval of regional lymph nodes (RORLN), and chemotherapy. The nomogram demonstrated good discriminative ability, with an area under the curve (AUC) of 83.8%. Patients with LM had significantly lower survival rates than those without LM (P < 0.001). Survival analysis revealed that advanced age, tumor location in the duodenum, surgery, RORLN and chemotherapy were associated with cancer-specific survival (CSS) in patients with LM originating from SBA.

This study highlights the significant impact of LM on the survival of SBA patients and identifies key risk factors for its occurrence. The developed nomogram aids in targeted screening and personalized treatment planning.

Small bowel cancer (SBC) is a rare and aggressive disease with a poor prognosis, necessitating the exploration of novel treatment approaches. This narrative review examines the current evidence on targeted therapy and immunotherapy for SBC, focusing on the two most common subtypes: adenocarcinoma and neuroendocrine tumor. A comprehensive search of PubMed, Scopus, and Google Scholar databases was conducted to identify relevant clinical trials and case reports published in English up to September 2023. The review includes 17 clinical trials and 10 case reports, indicating that targeted therapy and immunotherapy can have the potential to improve survival rates in patients with SBC. Notably, promising targeted medicines include bevacizumab, cetuximab, and trastuzumab, while pembrolizumab and nivolumab show potential as immunotherapies. However, it should be noted that the magnitude of the increase in survival rates with these interventions was small. Further research is needed to determine the optimal combination of targeted therapy and immunotherapy for individual patients with SBC.

Small bowel adenocarcinoma is a rare disease. The genomic profiling tumours according to clinical characteristics and its impact on the prognosis remains unclear.

A pooled analysis of clinical data, genomic profiling and MisMatch Repair (MMR) status from three databases was performed.

A total of 188 tumour samples were analysed. A predisposing disease was reported in 22.3%, mainly Lynch syndrome and Crohn's disease. The tumours were localized in 80.2% and metastatic in 18.8%. The most frequent mutations were KRAS (42.0%) among them 7/79 are G12C, TP53 (40.4%), APC (19.1%), PIK3CA (18.6%), SMAD4 (12.8%) and ERBB2 (9.6%). Mutation distribution differed according to predisposing disease for TP53, ERBB2, IDH1, FGFR3, FGFR1 and KDR. KRAS and SMAD4 mutations were more frequent in metastatic tumour, whereas ERBB2 mutations were absent in metastatic tumour. For localized tumour, APC mutation was independently associated with a poor overall survival (OS) (p = 0.0254). 31.8% of localized tumours and 11.3% of metastatic tumours were dMMR (29.8% of the entire cohort). A dMMR status was associated with a better OS (HR = 0.61 [0.39-0.96], p = 0.0316).

There is a different genomic profile according to the stage and predisposing disease. dMMR and APC mutation in localized tumour predict a better prognosis.

It is rare to find a small bowel tumour presenting as intestinal obstruction. This type of cancer is an extremely unusual condition often misdiagnosed until late stages. We report the case of a patient with persistent vomiting secondary to an obstructing jejunal adenocarcinoma not related to intestinal bowel disease. After resection and chemotherapy treatment a huge mass was detected in the left ovary. The anatomopathological findings confirmed a metastatic cancer consequent to the jejunal adenocarcinoma previously resected. This case illustrates a successful outcome of a jejunal adenocarcinoma with very poor prognosis after a extremely unusual ovarian metastasis. It is highly important to suspect other causes than intestinal bowel disease when doing a differential diagnosis in a young patient presenting with clinical symptoms of intestinal obstruction.

Endoscopic resection (ER) for jejunoileal lesions (JILs) has been technically challenging. We aimed to characterize the clinicopathologic characteristics, feasibility, and safety of ER for JILs.

We retrospectively investigated 52 patients with JILs who underwent ER from January 2012 to February 2022. We collected and analyzed clinicopathological characteristics, procedure-related parameters, outcomes, and follow-up data.

The mean age was 49.4 years. Of the 52 JILs, 33 ileal tumors within 20 cm from the ileocecal valve were resected with colonoscopy, while 19 tumors in the jejunum or the ileum over 20 cm from the ileocecal valve received enteroscopy resection. The mean procedure duration was 49.0 min. The en bloc resection and en bloc with R0 resection rates were 86.5% and 84.6%, respectively. Adverse events (AEs) included one (1.9%) major AE (delayed bleeding) and five (9.6%) minor AEs. During a median follow-up of 36.5 months, two patients had local recurrence (3.8%), while none had metastases. The 5-year recurrence-free survival (RFS) and disease-specific survival (DSS) were 92.9% and 94.1%, respectively. Compared with the enteroscopy group, overall AEs were significantly lower in the colonoscopy group (P < 0.05), but no statistical differences were observed in RFS (P = 0.412) and DSS (P = 0.579). There were no significant differences in AEs, RFS, and DSS between the endoscopic submucosal dissection (ESD) and the endoscopic mucosal resection (EMR) group.

ER of JILs has favorable short-term and long-term outcomes. Both ESD and EMR can safely and effectively resect JILs in appropriately selected cases.

In this editorial we comment on the article published "Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment". Small bowel adenocarcinoma (SBA) is a rare gastrointestinal neoplasm and despite the small intestine's significant surface area, SBA accounts for less than 3% of such tumors. Early detection is challenging and the reason arises from its asymptomatic nature, often leading to late-stage discovery and poor prognosis. Treatment involves platinum-based chemotherapy with a 5-fluorouracil combination, but the lack of effective chemotherapy contributes to a generally poor prognosis. SBAs are linked to genetic disorders and risk factors, including chronic inflammatory conditions. The unique characteristics of the small bowel, such as rapid cell renewal and an active immune system, contributes to the rarity of these tumors as well as the high intratumoral infiltration of immune cells is associated with a favorable prognosis. Programmed cell death-ligand 1 (PD-L1) expression varies across different cancers, with potential discrepancies in its prognostic value. Microsatellite instability (MSI) in SBA is associated with a high tumor mutational burden, affecting the prognosis and response to immunotherapy. The presence of PD-L1 and programmed cell death 1, along with tumor-infiltrating lymphocytes, plays a crucial role in the complex microenvironment of SBA and contributes to a more favorable prognosis, especially in the context of high MSI tumors. Stromal tumor-infiltrating lymphocytes are identified as independent prognostic indicators and the association between MSI status and a favorable prognosis, emphasizes the importance of evaluating the immune status of tumors for treatment decisions.

Crohn's Disease (CD) is an Inflammatory Bowel Disease and is characterized by an immune-mediated nature. Its etiology results from the interaction between genetic, enviromental and microbial factors. Regarding pathophysiology, it involves high levels of interleukin (IL)-12, IL-17, and Th1 profile, along with loss of tolerance mechanisms, an increase in pro-inflammatory interleukins, beyond the possibility to affect any part of the gastrointestinal tract. Its symptoms include abdominal pain, chronic diarrhea, weight loss, anorexia, and fatigue, as well as blood in the stool or rectum. Additionally, conditions comprising musculoskeletal, cutaneous, ocular, hepatic, and hematological alterations may be associated with this scenario and extra-intestinal presentation, such as erythema nodosum, anterior uveitis, osteoporosis, and arthritis can also occur. Today, clinical history, exams as fecal calprotectin, ileocolonocopy, and capsule endoscopy can be performed in the diagnosis investigation, along with treatments to induce and maintain remission. In this sense, anti-inflammatory drugs, such as corticosteroids, immunomodulators, and biological agents, as well as surgery and non-pharmacological interventions plays a role in its therapy. The aim of this review is to bring more current evidence to clinical management of CD, as well as to briefly discuss aspects of its pathophysiology, surveillance, and associated disorders.

Epstein-Barr virus (EBV)-positive mucocutaneous ulcers (MCUs) are an uncommon disorder characterized by ulcerative lesions in the skin, oral cavity or gastrointestinal tract in patients with iatrogenic or aging-induced immunosuppression. The nonspecific lesions are difficult to differentiate from small bowel adenocarcinomas. We present the case of a 69-year-old woman who was initially misdiagnosed with a small bowel adenocarcinoma but was later surgically diagnosed with and treated for EBV-MCU. Through this case, we aim to emphasize the importance of accurately distinguishing between the two conditions.

The patient presented with an incidental finding of a small bowel tumor during computed tomography (CT) examination performed for hematuria. The CT scan showed irregular thickening of the distal ileum, which was suggestive of a malignant small bowel tumor. An exploratory laparotomy revealed an 8-cm mass in the distal ileum; thus, a segment of the small intestine, including the mass, was resected. Histopathological analysis revealed an ulceroinfiltrative mass-like lesion with luminal narrowing, marked inflammatory cell infiltration, and large atypical lymphoid cells (positive for EBV-encoded small RNA). A final diagnosis of an EBV-MCU was established. The postoperative course was uneventful, and the patient was discharged on postoperative day 7. The patient remained recurrence-free until 12 mo after surgery.

This case highlights the diagnostic challenges for EBV-MCUs and emphasizes the importance of comprehensive evaluation and accurate histopathological analysis.

Small bowel adenocarcinoma (SBA) is a rare cancer with an aggressive behavior. No study has specifically addressed the putative prognostic role of mismatch repair status in stage III SBAs.

We aimed to investigate whether mismatch repair deficiency is associated with cancer-specific survival in a Western cohort of patients with stage III SBAs.

In this retrospective multicentric international cohort study, we enrolled 70 patients who underwent surgically resection for stage III SBAs and we analyzed the frequency of mismatch repair deficiency, tested by immunohistochemistry for mismatch repair proteins and by polymerase chain reaction for microsatellite instability, and its association with cancer-specific survival and other clinic-pathologic factors.

We found sixteen (23%) patients with mismatch repair deficient adenocarcinoma, without discordance between immunohistochemical and polymerase chain reaction for microsatellite instability analyses. Mismatch repair deficiency proved to be associated with a better outcome both at univariable analysis (hazard ratio: 0.28, 95% confidence interval: 0.08-0.91, p: 0.035) and in bivariable models adjusted for patient age or gender, tumor site, pT4 stage, tumor budding, and perineural invasion.

This study highlights the importance of testing mismatch repair status to improve prognostic stratification in stage III SBAs.

Background and Objectives: Small bowel adenocarcinomas (SBAs) are rare tumors of the gastrointestinal system. Lymph node metastasis in patients with curatively resected SBAs is associated with poor prognosis. In this study, we determined the prognostic utility of the number of removed lymph nodes and the metastatic lymph node ratio (the N ratio). Materials and Methods: The data of 97 patients who underwent curative SBA resection in nine hospitals of Turkey were retrospectively evaluated. Univariate and multivariate analyses of potentially prognostic factors including the N ratio and the numbers of regional lymph nodes removed were evaluated. Results: Univariate analysis showed that perineural and vascular invasion, metastatic lymph nodes, advanced TNM stage, and a high N ratio were significant predictors of poor survival. Multivariate analysis revealed that the N ratio was a significant independent predictor of disease-specific survival (DSS). The group with the lowest N ratio exhibited the longest disease-free survival (DFS) and DSS; these decreased significantly as the N ratio increased (both, p < 0.001). There was no significant difference in either DFS or DSS between groups with low and high numbers of dissected lymph nodes (i.e., <13 and ≥13) (both, p = 0.075). Conclusions: We found that the N ratio was independently prognostic of DSS in patients with radically resected SBAs. The N ratio is a convenient and accurate measure of the severity of lymph node metastasis.

Small intestine cancer is rare, accounting for approximately 3% of all gastrointestinal malignancies. The most common histological subtypes include adenocarcinoma, neuroendocrine tumours (NETs) and gastrointestinal stromal tumours (GISTs). In localised disease, surgery remains the mainstay of treatment and the best approach to improve survival. Current treatment for small intestine adenocarcinoma (SIA) is extrapolated from small studies and data from colorectal cancer (CRC). There is limited evidence to guide therapy in the adjuvant setting. However, there are small phase II studies in the advanced setting providing evidence for the role of chemotherapy and immunotherapy. There is also limited evidence assessing the efficacy of targeted therapies. Small intestine NETs are rare, with evidence for somatostatin analogue therapy, particularly in the low to intermediate-grade well-differentiated tumours. Poorly differentiated NETs are generally managed with chemotherapy but have worse outcomes compared with well-differentiated NETs. The management of small intestine GISTs is largely targeting KIT mutations with imatinib. Recent trials have provided evidence for effective therapies in imatinib-resistant tumours and the potential role of immunotherapy. The aim of this article was to review the evidence for the current management and recent advances in the management of small intestine adenocarcinoma, NETs and GISTs.

Small bowel adenocarcinomas (SBAs) are rare and there is little comprehensive data on SBA genomic alterations for Asian patients. This study aimed to profile genomic alterations of SBA in Japanese patients using targeted next-generation sequencing (NGS).

We examined 22 surgical resections from patients with primary SBA. SBA genomic alterations were analyzed by NGS. Mismatch repair (MMR) status was determined by immunohistochemical analysis. Mucin phenotypes were classified as gastric (G), intestinal (I), gastrointestinal (GI), and null (N) types on MUC2, MUC5AC, MUC6, and CD10 immunostaining.

The most common genomic alterations found in SBA tumors were TP53 (n = 16), followed by KRAS (n = 6), APC (n = 5), PIK3CA (n = 4), CTNNB1 (n = 3), KIT (n = 2), BRAF (n = 2), CDKN2A (n = 2), and PTEN (n = 2). Deficient MMR tumors were observed in 6 out of 22 patients. Tumor mucin phenotypes included 2 in G-type, 12 in I-type, 3 in GI-type, and 5 in N-type. APC and CTNNB1 mutations were not found in G-type and GI-type tumors. KRAS mutations were found in all tumor types except for G-type tumors. TP53 mutations were found in all tumor types. Although no single gene mutation was associated with overall survival (OS), we found that KRAS mutations were associated with significant worse OS in patients with proficient MMR tumors.

SBA genomic alterations in Japanese patients do not differ significantly from those reports in Western countries. Tumor localization, mucin phenotype, and MMR status all appear to impact SBA gene mutations.