Multiple sarcomatoid carcinomas in the small intestine with perforation: A case report and literature review.

RATIONALE: Sarcomatoid carcinoma of the small intestine is an exceedingly rare and aggressive malignancy, often diagnosed at advanced stages with a poor prognosis. This study documents a detailed case of sarcomatoid carcinoma of the small intestine, highlighting the diagnostic challenges and treatment approaches, underscored by a comprehensive review of related literature. Given the rarity of this condition, our report aims to enrich the existing diagnostic and treatment frameworks for this malignancy, emphasizing the necessity for early detection and intervention strategies. By presenting this case in conjunction with a literature review, we seek to shed light on the elusive nature of sarcomatoid carcinoma in the small intestine and propose avenues for improving patient outcomes. PATIENT CONCERNS: Case presentation A 61-year-old male patient initially presented with recurrent abdominal pain and gastrointestinal symptoms. Initial abdominal computed tomography (CT) scans and gastrointestinal endoscopy revealed only inflammatory and hyperplastic changes in the duodenum and jejunum, with a diagnosis of intestinal obstruction. Two years later, due to gastrointestinal perforation, the patient was hospitalized again. DIAGNOSES: CT scans and other examinations revealed small intestinal lesions. Four small intestinal lesions were surgically removed, and pathology and immunohistochemistry confirmed sarcomatoid carcinoma of the small intestine. A short time later, enhanced CT scans revealed metastatic lesions in the hepatic portal and adrenal glands. INTERVENTIONS: After surgery, the gastrointestinal function gradually recovered, and the patient was discharged from the hospital on a semiliquid diet. No further treatment such as radiotherapy or chemotherapy was administered postoperatively. OUTCOMES: Five months after the surgery, the patient died due to brain metastasis. LESSONS: The study outcomes reveal the aggressive nature of sarcomatoid carcinoma of the small intestine, characterized by rapid progression and poor prognosis despite surgical interventions. The patient condition rapidly deteriorated, leading to metastasis and death within 5 months postsurgery. These findings underscore the critical need for early detection and possibly innovative treatment approaches to improve survival rates. This case also highlights the potential for gastrointestinal sarcomatoid carcinoma to metastasize to distant organs, including the brain, suggesting a propensity for hematogenous spread.

Toll-like receptors 1-9 in small bowel neuroendocrine tumors-Clinical significance and prognosis.

Toll-like receptors (TLRs) are pattern recognition receptors of the innate immunity. TLRs are known to mediate both antitumor effects and tumorigenesis. TLRs are abundant in many cancers, but their expression in small bowel neuroendocrine tumors (SB-NETs) is unknown. We aimed to characterize the expression of TLRs 1-9 in SB-NETs and lymph node metastases and evaluate their prognostic relevance. The present study included 125 patients with SB-NETs, of whom 95 had lymph node metastases, from two Finnish hospitals. Tissue samples were stained immunohistochemically for TLR expression, assessed based on cytoplasmic and nucleic staining intensity and percentage of positively stained cells. Statistical methods for survival analysis included Kaplan-Meier method and Cox regression adjusted for confounding factors. Disease-specific survival (DSS) was the primary outcome. TLRs 1-2 and 4-9 were expressed in SB-NETs and lymph node metastases. TLR3 showed no positive staining. In primary SB-NETs, TLRs 1-9 were not associated with survival. For lymph node metastases, high cytoplasmic TLR7 intensity associated with worse DSS compared to low cytoplasmic intensity (26.4% vs. 84.9%, p = 0.028). Adjusted mortality hazard (HR) was 3.90 (95% CI 1.07-14.3). The expression of TLRs 1-6 and 8-9 in lymph node metastases were not associated with survival. SB-NETs and their lymph node metastases express cytoplasmic TLR 1-2 and 4-9 and nucleic TLR5. High TLR7 expression in SB-NET lymph node metastases was associated with worse prognosis. The current research has future perspective, as it can help create base for clinical drug trials to target specific TLRs with agonists or antagonists to treat neuroendocrine tumors.

Chylomicron retention disease: a rare aetiology of failure to thrive.

The aetiology of failure to thrive (FTT) in children is broad, of which some conditions are extremely rare. It is important to consider these rarer conditions, especially in the setting of other concerning signs/symptoms or when there is no improvement with conventional treatment. In this case report we highlight such a rare condition-chylomicron retention disease (CRD) as an aetiology of FTT. CRD often presents with non-specific symptoms, resulting in delayed diagnosis which is established by genetic workup and histology from small intestinal biopsies. Despite being rare, CRD needs to be considered as one of the differential diagnoses after ruling out the more common causes of FTT.

Prevalence of metastases outside the liver and abdominal lymph nodes on 68Ga-DOTATOC-PET/CT in patients with small intestinal and pancreatic neuroendocrine tumours.

Metastases outside the liver and abdominal/retroperitoneal lymph nodes are nowadays detected frequently in patients with neuroendocrine tumours (NETs), owing to the high sensitivity of positron emission tomography (PET) with Gallium-68-DOTA-somatostatin analogues (68Ga-SSA) and concomitant diagnostic computed tomography (CT). Our aim was to determine the prevalence of extra-abdominal metastases on 68Ga-DOTATOC-PET/CT in a cohort of patients with small intestinal (Si-NET) and pancreatic NET (Pan-NET), as well as that of pancreatic metastasis in patients with Si-NET. Among 2090 patients examined by 68Ga-DOTATOC-PET/CT at two tertiary referral centres, a total of 1177 patients with a history of Si- or Pan-NET, were identified. The most recent 68Ga-DOTATOC-PET/CT report for each patient was reviewed, and the location and number of metastases of interest were recorded. Lesions outside the liver and abdominal nodes were found in 26% of patients (n = 310/1177), of whom 21.5% (255/1177) were diagnosed with Si-NET and 4.5% (55/1177) Pan-NET. Bone metastases were found in 18.4% (215/1177), metastases to Virchow's lymph node in 7.1% (83/1177), and lung/pleura in 4.8% (56/1177). In the subset of 255 Si-NET patients, 5.4% (41/255) manifested lesions in the pancreas, 1.5% in the breast (18/255), 1.3% in the heart (15/255) and 1% in the orbita (12/255). In Si-NET patients, the Ki-67 proliferation index was higher in those with ≥2 metastatic sites of interest, than with 1 metastatic site, (p <0.001). Overall, extra-abdominal or pancreatic metastases were more often found in patients with Si-NET (34%) than in those with Pan-NET (13%) (p <0.001). Bone metastases were 2.6 times more frequent in patients with Si-NET compared to Pan-NET patients (p <0.001). Lesions to the breast and orbita were encountered in almost only Si-NET patients. In conclusion, lesions outside the liver and abdominal nodes were detected in as many as 26% of the patients, with different prevalence and metastatic patterns in patients with Si-NET compared to Pan-NET. The impact of such metastases on overall survival and clinical decision-making needs further evaluation.

Combined effects of radiation and simulated microgravity on intestinal tumorigenesis in C3B6F1 ApcMin/+ mice.

Explorations of the Moon and Mars are planned as future manned space missions, during which humans will be exposed to both radiation and microgravity. We do not, however, know the health effects for such combined exposures. In a ground-based experiment, we evaluated the combined effects of radiation and simulated microgravity on tumorigenesis by performing X-irradiation and tail suspension in C3B6F1 ApcMin/+ mice, a well-established model for intestinal tumorigenesis. Mice were irradiated at 2 weeks of age and underwent tail suspension for 3 or 11 weeks using a special device that avoids damage to the tail. The tail suspension treatment significantly reduced the thymus weight after 3 weeks but not 11 weeks, suggesting a transient stress response. The combination of irradiation and tail suspension significantly increased the number of small intestinal tumors less than 2 mm in diameter as compared with either treatment alone. The combined treatment also increased the fraction of malignant tumors among all small intestinal tumors as compared with the radiation-only treatment. Thus, the C3B6F1 ApcMin/+ mouse is a useful model for assessing cancer risk in a simulated space environment, in which simulated microgravity accelerates tumor progression when combined with radiation exposure.

[A Case of Five Years Recurrence-Free Survival after Successful Multidisciplinary Treatment for Simultaneous Brain Metastasis and Heterochronic Small Intestinal Metastasis from Lung Cancer].

The patient was a 54-year-old male at the time of initial examination. He was aware of numbness and weakness in the left hemisphere of his body and came to see the hospital. He was diagnosed with brain metastasis of lung cancer and started treatment(cT2N0M1[Brain]). He underwent gamma knife for the head lesion and nivolumab for the lung lesion. The patient's lesions shrank with the success of the medical treatment, but recurred with small intestinal metastasis. He underwent a partial resection of the small intestine and was treated again with nivolumab, which resulted in a complete response. He is currently alive without recurrence. We have experienced a very rare case of recurrence-free survival after treatment for brain metastasis and small intestinal metastasis of lung cancer.

Capsule endoscopy and panendoscopy: A journey to the future of gastrointestinal endoscopy.

In 2000, the small bowel capsule revolutionized the management of patients with small bowel disorders. Currently, the technological development achieved by the new models of double-headed endoscopic capsules, as miniaturized devices to evaluate the small bowel and colon [pan-intestinal capsule endoscopy (PCE)], makes this non-invasive procedure a disruptive concept for the management of patients with digestive disorders. This technology is expected to identify which patients will require conventional invasive endoscopic procedures (colonoscopy or balloon-assisted enteroscopy), based on the lesions detected by the capsule, i.e., those with an indication for biopsies or endoscopic treatment. The use of PCE in patients with inflammatory bowel diseases, namely Crohn's disease, as well as in patients with iron deficiency anaemia and/or overt gastrointestinal (GI) bleeding, after a non-diagnostic upper endoscopy (esophagogastroduodenoscopy), enables an effective, safe and comfortable way to identify patients with relevant lesions, who should undergo subsequent invasive endoscopic procedures. The recent development of magnetically controlled capsule endoscopy to evaluate the upper GI tract, is a further step towards the possibility of an entirely non-invasive assessment of all the segments of the digestive tract, from mouth-to-anus, meeting the expectations of the early developers of capsule endoscopy.

A 58-Year-Old Woman with Acute Torsion of the Small Bowel Due to Diffuse Intestinal Lipomatosis.

BACKGROUND Diffuse intestinal lipomatosis is a rare condition that infiltrates mature fatty tissue into the intestinal submucosa and subserosa of the small or large intestine and can present with intestinal obstruction or torsion. This report is of the case of a 58-year-old woman who had acute torsion of the small bowel due to diffuse small intestinal lipomatosis. CASE REPORT A 58-year-old woman, who was otherwise in good health, arrived at our Emergency Department experiencing sudden, intense pain in the lower abdomen. She also reported abdominal swelling, feelings of nausea, vomiting, and reduced ability to defecate for at least 2 days. The next morning, contrast-enhanced abdominal computed tomography (CT) scan was performed, showing diffuse thickening of the small intestinal wall with hypodensity, fatty density, lumen narrowing, and wall thinning. The small intestine demonstrated a whirlpool-like distribution in the lower right abdomen and localized thickening of the small intestinal wall, suggesting acute intestinal torsion. An hour later, an emergency operation was performed to remove part of the small intestine. Three days later, pathological results showed a thin intestinal wall, expansion of the mucosal layer and submucosa, and hyperplasia of adipose tissue. CONCLUSIONS This report presents a rare case of torsion and small bowel obstruction caused by diffuse intestinal lipomatosis and focuses on the abdominal enhanced CT scan, which showed diffuse thickening of the small intestine, with multiple areas of fat density and torsion of the small intestine in the right lower abdomen. Histopathology is also presented, with the result showing intestinal lipomatosis.

[Early Duodenal Cancer Resected by Using Laparoscopic and Endoscopic Assistance Surgery in a Patient with Peutz-Jeghers Syndrome].

A 28-year-old female with a history of treatment for small intestinal polyps and characteristic pigmentation of her lip was clinically diagnosed with Peutz-Jeghers syndrome(PJS). Her sister had the pathogenic variant of STK11 upon genetic testing. A 20-mm polyp was identified in the second part the patient's duodenum on routine gastrointestinal surveillance, and biopsy revealed a well-differentiated adenocarcinoma. Laparoscopic partial duodenectomy with endoscopy was planned. After confirming the location of the tumor and Kocherization using a laparoscope, the polyp was resected via submucosal dissection under direct visualization with a small incision. The polyp was diagnosed as well-differentiated adenocarcinoma in situ and was resected without remnants. PJS is characterized by a high incidence of malignant tumors, and lifelong surveillance for gastrointestinal and extra-gastrointestinal tumors is necessary. The incidence of duodenal cancer is not high among patients with PJS. However, surgery for advanced cancer is highly invasive. It is desirable to detect the tumors at an early stage so that they can be resected via a less invasive treatment method such as endoscopic resection or laparoscopic surgery with an endoscope.

[A Case of Desmoid-Type Fibromatosis of the Mesentery of Small Intestine].

Desmoid-type fibromatosis is a relatively rare disease, often associated with familial adenomatous polyposis and a history of abdominal surgery. A 43-year-old male patient presented with abdominal pain and contrast-enhanced CT showed a mass in the lower abdomen. The mass was a 4×4×3 cm white, dense tumor with a wreath-like arrangement of eosinophilic spindle-shaped cells. Immunostaining showed KIT(-), CD34(-), desmin(-), ß-catenin(+), SMA(few+), and the diagnosis was desmoid-type fibrosis. Six months after surgery, there was no apparent recurrence.

Metastatic melanoma to small bowel: metastasectomy is supported in the era of immunotherapy and checkpoint inhibitors.

BACKGROUND: Metastatic melanoma to the small bowel is an aggressive disease often accompanied by obstruction, abdominal pain, and gastrointestinal bleeding. With advancements in melanoma treatment, the role for metastasectomy continues to evolve. Inclusion of novel immunotherapeutic agents, such as checkpoint inhibitors, into standard treatment regimens presents potential survival benefits for patients receiving metastasectomy. CASE PRESENTATION: We report an institutional experience of 15 patients (12 male, 3 female) between 2014-2022 that underwent small bowel metastasectomy for metastatic melanoma and received perioperative systemic treatment. Median age of patients was 64 years (range: 35-83 years). No patients died within 30 days of their surgery, and the median hospital length of stay was 5 days. Median overall survival in these patients was 30.1 months (range: 2-115 months). Five patients died from disease (67 days, 252 days, 426 days, 572 days, 692 days postoperatively), one patient died of non-disease related causes (1312 days postoperatively), six patients are alive with disease, and three remain disease free. CONCLUSIONS: This case series presents an updated perspective of the utility of metastasectomy for small bowel metastasis in the age of novel immunotherapeutic agents as standard systemic treatment. Small bowel metastasectomy for advanced melanoma performed in conjunction with perioperative systemic therapy is safe and appears to promote long-term survival and enhanced quality of life.

Clinicopathological and molecular genetic alterations in monomorphic-epitheliotropic intestinal T-cell lymphoma of the small intestine.

BACKGROUND: Small intestinal monomorphic-epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare aggressive T-cell lymphoma originating in the gastrointestinal tract. This study aimed to investigate the clinicopathological features, immunophenotypes, and molecular genetic changes of MEITL. METHODS: The clinicopathological data for three patients with surgically resected MEITL of the small intestine were collected. Next, immunohistochemical labeling, Epstein-Barr virus (EBV) in situ hybridization, assessment of clonal rearrangement of T-cell receptor (TCR) genes, and next-generation sequencing (NGS) were performed. RESULTS: Of the three patients, two were male and one was female, with ages of 61, 67, and 73 years, respectively. Clinical manifestations were predominantly abdominal pain and distension. Histopathology revealed infiltrative growth of small-to-medium-sized lymphocytes with a consistent morphology between the intestinal walls, accompanied by an obvious pro-epithelial phenomenon. The expression of CD3, CD8, CD43, CD56, TIA-1, CD103, H3K36me3, and Bcl-2 was detected, and the Ki-67 proliferation index ranged from 50% to 80%. All three patients tested negative for EBER. However, monoclonal rearrangement of the TCR gene was detected in them. NGS testing showed a JAK3 mutation in all three cases. Further, STAT5B, SETD2, and TP53 mutations were each observed in two cases, and a BCOR mutation was found in one case. All patients were treated with chemotherapy after surgery. Two patients died 7 and 15 month post-operation, and one patient survived for 5 months of follow-up. CONCLUSIONS: Our findings demonstrate that mutations in JAK3 and STAT5B of the JAK/STAT pathway and inactivation of the oncogene SETD2 markedly contribute to the lymphomagenesis of MEITL.

Age Is a Risk Factor for Gastroscopy-Assisted Capsule Endoscopy in Children.

BACKGROUND/AIMS: The aim of this study was to explore the risk factors for the incidence of gastroscopy-assisted capsule endoscopy and the small bowel transit time in pediatric patients who underwent capsule endoscopy examination. MATERIALS AND METHODS: A retrospective analysis was performed to analyze the clinical data collected from pediatric patients who underwent capsule endoscopy examination. RESULTS: A total of 239 pediatric patients were enrolled in this study. About 196 (82.0%) patients completed the entire small bowel capsule endoscopy examination, while 3 (1.3%) patients were subjected to capsule retention. Only age, not gender, height, body weight, body mass index, chief complaint, and intestinal preparation medications, has been identified as a risk factor for the incidence of gastroscopy-assisted capsule endoscopy (P < .05) by multivariate logistic regression. Further analysis showed that the small bowel transit time in the self-swallowed group was shorter than that in the gastroscopy-assisted group, while no significant difference was obtained in other factors, including intestinal preparation medications, metoclopramide, and lesions in the small intestine, which did not significantly affect small bowel transit time compared with the corresponding control group (P > .05). CONCLUSION: A comprehensive assessment is required before performing capsule endoscopy, because age has been identified as a critical risk factor for the incidence of gastroscopy-assisted capsule endoscopy in pediatric patients.

Monitoring coeliac disease in 2024, time to change practice?

PURPOSE OF REVIEW: Persistent villous atrophy is associated with morbidity in coeliac disease and most commonly due to ongoing gluten ingestion. Current methods for assessing gluten exposure and persisting villous atrophy include dietary questionnaires and repeat duodenal biopsy, which have limited accuracy or are invasive. This review discusses adjunctive and/or novel tests that could be used to overcome these challenges. RECENT FINDINGS: Small bowel capsule endoscopy is well tolerated and helps to evaluate for persisting villous atrophy and importantly, complications associated with coeliac disease. Testing for urinary and/or stool gluten immunogenic peptides may help identify recent gluten exposure, but further studies are still warranted to evaluate the accuracy and applicability of this approach. Measuring spikes in circulating Interleukin-2 following gluten challenge has shown promise for coeliac disease diagnosis, and thus may serve as a useful confirmatory test in those with persisting symptoms but provides no information on mucosal inflammation. No specific gut microbial signature has been identified in coeliac disease; however, studies have shown a reduced microbial diversity in active disease, which with future refinement may prove clinically useful. SUMMARY: There is no evidence to support alternative methods for assessing persisting villous atrophy in coeliac disease over performing an up-to-date duodenal biopsy. Monitoring for adherence to a gluten-free diet remains clinically challenging and should be a priority for future research.

Immune signature of small bowel adenocarcinoma and the role of tumor microenvironment.

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.

Clinical features and prognosis of malignant small bowel tumors: Experience from a university hospital in Chile.

BACKGROUND: Small bowel tumors (SBT) are infrequent and represent a small proportion of digestive neoplasms. There is scarce information about SBT in Latin America. AIM: To describe the epidemiology, clinical characteristics, diagnostic methods, and survival of malignant SBTs. METHODS: Retrospective observational study of adult patients with histopathological diagnosis of SBT between 2007 and 2021 in a university hospital in Chile. RESULTS: A total of 104 patients [51.9% men; mean age 57 years] with SBT. Histological type: neuroendocrine tumor (NET) (43.7%, n=38), gastrointestinal stromal tumors (GIST) (21.8%, n=19), lymphoma (17.2%, n=15) and adenocarcinoma (AC) (11.5%, n=10). GIST was more frequent in duodenum (50%; n=12) and NET in the ileum (65.8%; n=25). Metastasis was observed in 17 cases, most commonly from colon and melanoma. Nausea and vomiting were significantly more often observed in AC (p=0.035), as well as gastrointestinal bleeding in GIST (p=0.007). The most common diagnostic tools were CT and CT enteroclysis with an elevated diagnostic yield (86% and 94% respectively). The 5-year survival of GIST, NET, lymphoma and AC were 94.7% (95%CI: 68.1-99.2), 82.2% (95%CI: 57.6-93.3), 40.0% (95%CI: 16.5-82.8) and 25.9% (95%CI: 4.5-55.7%), respectively. NET (HR 6.1; 95%CI: 2.1-17.2) and GIST (HR 24.4; 95%CI: 3.0-19.8) were independently associated with higher survival compared to AC, adjusted for age and sex. CONCLUSIONS: Malignant SBT are rare conditions and NETs are the most common histological subtype. Clinical presentation at diagnosis, location or complications may suggest a more probable diagnosis. GIST and NET are associated with better survival compared to other malignant subtypes.