[Multiple myeloma with t (8;14) and t (11;14) and extramedullary infiltration of multiple organs].

A 69-year-old man presented with lumbago and was diagnosed with multiple myeloma (IgD-λ type, R-ISS stage II) with bone-destructive lesions in the lumbar spine and sacrum. Chromosome analysis showed t (8;14)(q24;q32) and t (11;14)(q13;q32). Treatment with daratumumab, lenalidomide, and dexamethasone resulted in partial response, but the disease relapsed, with a copy number increase in t (11;14) and abnormal amplification of the 1q21 region. The patient was treated for CMV enteritis, and was admitted to the hospital due to sudden abdominal pain. Gastrointestinal perforation was diagnosed by CT scan showing free air and wall thickening in the small intestine. Emergency surgery was performed, and the tumors in the perforated area were positive for CCND1 but negative for MYC on immunostaining. The patient's general condition did not improve after the surgery and he died. Pathological autopsy revealed extramedullary infiltration of multiple organs in addition to the small intestine. Extramedullary infiltration is thought to be caused by clonal evolution, and further research is warranted to clarify its pathogenesis and establish effective therapeutic strategies in high-risk patients.

A case report of small intestinal volvulus caused by lipomatosis of the small intestine successfully treated with enterectomy.

Small intestinal lipomatosis is a rare condition that presents a diagnostic challenge due to the absence of identifiable clinical symptoms and limitations of small intestine examination methods. Consequently, preoperative diagnosis is difficult and only a limited number of cases have been documented in the scientific literature. Here, we report a rare case of volvulus caused by small intestinal lipomatosis. A 58-year-old female patient was tentatively diagnosed with acute ileus. The whirl sign was detected using abdominal three-dimensional enhanced computed tomography, along with marked local intestinal dilation and multiple irregular fat-like containing lesions. During surgery, abnormal dilation of the small intestine between 80 and 220 cm from the ileocecal valve was detected and the affected intestine displayed a folded and twisted configuration. Examination of the resected intestine showed that the inner wall of the diseased intestinal lumen was covered with more than 100 lipomas of different sizes, the largest of which measured ~8.0 cm in diameter. Based on clinical symptoms alone, it was difficult to identify the cause of intestinal volvulus before surgery. Complete resection of the affected small intestine and subsequent pathological analysis yielded a definitive diagnosis of small intestinal lipomatosis. While small intestinal lipomatosis is a rare condition, prognosis is favorable if diagnosed early and treated appropriately. The application of three-dimensional enhanced computed tomography imaging can aid in accurate diagnosis, while complete resection of the affected small intestine is crucial to improve patient prognosis.

Ultra-high-frequency ultrasound (48-70 MHz) is a promising tool for improved gastrointestinal diagnostics in infants.

AIM: To investigate the clinical feasibility of ultra-high-frequency abdominal ultrasound (UHFUS) scans of preterm and term infants. METHODS: Prospectively, 19 healthy term newborn infants were examined with conventional ultrasound (CUS) (Toshiba, Aplio i700, linear probe 14L5) and UHFUS (Visualsonics VevoMD, linear probes UHF48 and UHF70) according to a standardised protocol. Measurements of wall thickness were performed for; stomach, small intestine, colon and peritoneum. Five preterm infants, with or without suspected necrotising enterocolitis (NEC), were also examined with UHF48. Of these, only one was later diagnosed with NEC. RESULTS: Differences between CUS and UHFUS (UHF48) were found in measurements of thickness; for peritoneum 0.25 versus 0.13 mm (p < 0.001), small intestine 0.76 versus 0.64 mm (p = 0.039) and colon 0.7 versus 0.47 mm (p < 0.001) in healthy term infants. Gaining frequency from 46 to 71 MHz showed a mean reduction in measurements of peritoneum from 0.13 to 0.09 mm (p < 0.001). One preterm infant with NEC showed a fivefold and twofold increase in peritoneal and gastrointestinal wall thickness respectively, compared to healthy preterm infants. CONCLUSION: UHFUS was a clinically feasible, promising method with potential to improve gastrointestinal diagnostics in infants. Lower peritoneum thickness and gastrointestinal wall thickness were demonstrated with UHFUS compared to CUS, suggesting an overestimation by CUS.

Primary mantle-cell lymphoma of small intestine presenting with intussusceptions: A case report and review of the literature.

INTRODUCTION AND IMPORTANCE: Mantle cell lymphoma is a rare type of non-Hodgkin's lymphoma which accounts for 5 % of all cases. Patients present with an advanced form of the disease. We present here a case of ileocolic intussusception secondary to mantle cell lymphoma which was revealed by abdominal pain and vomiting that was treated by surgical resection followed by chemotherapy. CASE PRESENTATION: This report illustrates the case of a 34-year-old male who presented with abdominal pain and vomiting. Imageology demonstrated an ileocolic intussusception which was treated with hemicolectomy followed by chemotherapy. Histopathology confirmed the diagnosis of Mantle cell lymphoma. CLINICAL DISCUSSION: Mantel cell lymphoma is a rare type of B-cell cancer. Patients are generally diagnosed with an advanced stage of the disease. Ileocolic intussusception is an uncommon presentation. Surgery is the pillar of the treatment. Resection depends on the extent and location of the lesion. Postoperative chemotherapy is crucial and it increases survival rate. CONCLUSION: Mantle cell lymphoma is a rare subgroup of B-cell lymphomas. Ileocolic intussusception is a complicated form of the disease. Surgery combined with chemotherapy is the mainstay of the treatment. Diagnosis is confirmed by histological analysis of the surgical specimen.

European Neuroendocrine Tumor Society (ENETS) 2024 guidance paper for the management of well-differentiated small intestine neuroendocrine tumours.

Both the incidence and prevalence of well-differentiated neuroendocrine tumours from the small intestine (Si-NET) are gradually increasing. Most patients have non-functioning tumours with subtle GI symptoms and tumours are often discovered incidentally by endoscopy or at advanced disease stages by imaging depicting mesenteric lymph node and /or liver metastases while around 30% of the patients present with symptoms of the carcinoid syndrome. Adequate biochemical assessment and staging including functional imaging is crucial for treatment-related decision-making that should take place in an expert multidisciplinary team setting. Preferably, patients should be referred to specialised ENETS Centres of Excellence or centres of high expertise in the field. This guidance paper provides the current evidence and best knowledge for the management of Si-NET grade (G) 1-3 following 10 key questions of practical relevance for the diagnostic and therapeutic decision making.

Improved Preservation of Rat Small Intestine Transplantation Graft by Introduction of Mesenchymal Stem Cell-Secreted Fractions.

Segmental grafts from living donors have advantages over grafts from deceased donors when used for small intestine transplantation. However, storage time for small intestine grafts can be extremely short and optimal graft preservation conditions for short-term storage remain undetermined. Secreted factors from mesenchymal stem cells (MSCs) that allow direct activation of preserved small intestine grafts. Freshly excised Luc-Tg LEW rat tissues were incubated in preservation solutions containing MSC-conditioned medium (MSC-CM). Preserved Luc-Tg rat-derived grafts were then transplanted to wild-type recipients, after which survival, injury score, and tight junction protein expression were examined. Luminance for each graft was determined using in vivo imaging. The findings indicated that 30-100 and 3-10 kDa fractions of MSC-CM have superior activating effects for small intestine preservation. Expression of the tight-junction proteins claudin-3, and zonula occludens-1 preserved for 24 h in University of Wisconsin (UW) solution containing MSC-CM with 50-100 kDa, as shown by immunostaining, also indicated effectiveness. Reflecting the improved graft preservation, MSC-CM preloading of grafts increased survival rate from 0% to 87%. This is the first report of successful transplantation of small intestine grafts preserved for more than 24 h using a rodent model to evaluate graft preservation conditions that mimic clinical conditions.

Bioengineered human colon organoids with in vivo-like cellular complexity and function.

Organoids and organs-on-a-chip have emerged as powerful tools for modeling human gut physiology and disease in vitro. Although physiologically relevant, these systems often lack the environmental milieu, spatial organization, cell type diversity, and maturity necessary for mimicking human intestinal mucosa. To instead generate models closely resembling in vivo tissue, we herein integrated organoid and organ-on-a-chip technology to develop an advanced human organoid model, called "mini-colons." By employing an asymmetric stimulation with growth factors, we greatly enhanced tissue longevity and replicated in vivo-like diversity and patterning of proliferative and differentiated cell types. Mini-colons contain abundant mucus-producing goblet cells and, signifying mini-colon maturation, single-cell RNA sequencing reveals emerging mature and functional colonocytes. This methodology is expanded to generate microtissues from the small intestine and incorporate additional microenvironmental components. Finally, our bioengineered organoids provide a precise platform to systematically study human gut physiology and pathology, and a reliable preclinical model for drug safety assessment.

An iPSC-derived small intestine-on-chip with self-organizing epithelial, mesenchymal, and neural cells.

Human induced pluripotent stem cell (hiPSC)-derived intestinal organoids are valuable tools for researching developmental biology and personalized therapies, but their closed topology and relative immature state limit applications. Here, we use organ-on-chip technology to develop a hiPSC-derived intestinal barrier with apical and basolateral access in a more physiological in vitro microenvironment. To replicate growth factor gradients along the crypt-villus axis, we locally expose the cells to expansion and differentiation media. In these conditions, intestinal epithelial cells self-organize into villus-like folds with physiological barrier integrity, and myofibroblasts and neurons emerge and form a subepithelial tissue in the bottom channel. The growth factor gradients efficiently balance dividing and mature cell types and induce an intestinal epithelial composition, including absorptive and secretory lineages, resembling the composition of the human small intestine. This well-characterized hiPSC-derived intestine-on-chip system can facilitate personalized studies on physiological processes and therapy development in the human small intestine.

Clinical application and feasibility of capsule endoscopy in children at a medical center in central Taiwan.

BACKGROUND PURPOSE: Capsule endoscopy (CE) is a noninvasive examination for excellent visualization of small bowel mucosal lesions. We aimed to evaluate the clinical efficacy and safety of CE in pediatric patients. METHODS: From April 2014 to December 2022, CE procedures performed in children younger than 18 years of age at Taichung Veteran General Hospital were analyzed retrospectively. RESULTS: Among 136 procedures, the completion rate was 95.6% (n = 130), with a median age of 14 years old. Suspicion or evaluation of inflammatory bowel diseases (IBD) (41%) was the most common indication for CE. Other common indications of CE were chronic unexplained abdominal pain (35%) and obscure gastrointestinal bleeding or iron deficiency anemia (21%). No procedure-related complications occurred. The diagnosis of those patients with incomplete study were CD with small bowel stricture, graft-versus-host disease and duodenal ulcers. A total of 86 CE procedures showed positive findings, and the overall diagnostic yield rate was 63.2%. Small bowel ulcers (65.12%) were the most common findings. Overall, 26.5% of CE examinations resulted in a new diagnosis and 44.9% of CE exams led to a change in therapy. For patients with IBD, CE findings resulted in an even higher therapeutic change rate of 48.1%. CONCLUSIONS: CE is a safe and feasible diagnostic method to study the small intestine in children, especially for IBD. Incomplete study could be an indicator of positive finding and can potentially be a guide to identify the site of possible strictures.

Intraluminal oxygen can keep small bowel mucosa intact in a segmental ischemia model.

Intestinal preservation for transplantation is accompanied by hypoperfusion with long periods of ischemia with total blood cessation and absolute withdrawal of oxygen leading to structural damage. The application of intraluminal oxygen has been successfully tested in small-animal series during storage and transport of the organ but have been so far clinically unrelatable. In this study, we tested whether a simple and clinically approachable method of intraluminal oxygen application could prevent ischemic damage in a large animal model, during warm ischemia time. We utilised a local no-flow ischemia model of the small intestine in pigs. A low-flow and high-pressure intraluminal oxygen deliverance system was applied in 6 pigs and 6 pigs served as a control group. Mucosal histopathology, hypoxia and barrier markers were evaluated after two hours of no-flow conditions, in both treatment and sham groups, and in healthy tissue. Macro- and microscopically, the luminal oxygen delivered treatment group showed preserved small bowel's appearance, viability, and mucosal integrity. A gradual deterioration of histopathology and barrier markers and increase in hypoxia-inducible factor 1-α expression towards the sites most distant from the oxygen application was observed. Intraluminal low-flow, high oxygen delivery can preserve the intestinal mucosa during total ischemia of the small intestine. This finding can be incorporated in methods to overcome small bowel ischemia and improve intestinal preservation for transplantation.

Comparing the Effects of Anti-TNF Agent and Ustekinumab on Small Bowel Inflammation in Crohn's Disease: Inverse Probability Weighting With Stabilized Weights of Propensity Scores.

Background: Endoscopic mucosal healing serves as a critical predictor for achieving long-term remission in Crohn's disease treatment. Recent data indicate that the effectiveness of healing varies based on the location of gastrointestinal inflammation. Additionally, reports suggest that antitumor necrosis factor-α (anti-TNF-α) agents exhibit reduced efficacy in treating small intestinal inflammation compared to colorectal inflammation. Conversely, limited research exists regarding the impact of the anti-IL12/23 agent ustekinumab (UST) on small intestinal inflammation. This study aimed to compare the effects of anti-TNF-α agents and UST on small intestinal inflammation using propensity score analysis. Methods: This retrospective observational study involved 70 patients with Crohn's disease who had inflammation in the small intestine and had initiated treatment with either anti-TNF agents or UST between March 2015 and August 2021. Endoscopic findings were evaluated before treatment commencement and at 1-2 years post-treatment initiation. The propensity score was employed to compare the efficacy of TNF agents and UST on small bowel inflammation. Results: Ustekinumab exhibited greater improvement in the small intestinal endoscopy score than anti-TNF-α antibodies according to the propensity score analysis (inverse probability weighting; P = .0448). However, no significant disparity was observed in the overall improvement of endoscopic scores between UST and anti-TNF-α antibodies (P = .5938). Conclusions: This study suggests that UST might be more effective than anti-TNF-α agents in treating small intestinal inflammation in Crohn's disease.

Primary Malignant Melanoma of the Small Intestine Presenting with Peritonitis: A Case Report.

Malignant melanoma of the small intestine is mostly a metastatic tumor of other primary lesions, especially of skin origin. Primary malignant melanoma of the small intestine is very uncommon. The clinical presentation is usually nonspecific, thus leading to late diagnosis. We report a 42-year-old man who presented to the emergency department of Imam-Reza Hospital with symptoms and signs of peritonitis and was a candidate for emergency laparotomy and enterectomy. The medical and family history were unremarkable. A bulky mass was seen 190 cm away from the Treitz band, and a diagnosis of malignant melanoma was confirmed by histologic and immunohistochemical study. Further clinical examination revealed no primary tumor elsewhere, so the diagnosis of primary small intestinal melanoma was concluded. Although metastatic malignant melanoma in the GI tract is common, the primary one is a very rare entity. The diagnosis could be challenging because a thorough investigation is needed to rule out the possible initial origin.

γδ intraepithelial lymphocytes acquire the ability to produce IFN-γ in a different time course than αß intraepithelial lymphocytes.

An age-dependent increase in IFN-γ expression by intestinal intraepithelial lymphocytes (IELs) contributes to the acquisition of resistance to infection by pathogens. However, how IELs acquire the ability to produce IFN-γ remains to be elucidated. Here, we report that IELs in the small intestine acquire the ability to rapidly produce IFN-γ at two distinct life stages. TCRαß+ IELs (αßIELs) started producing IFN-γ at 4 weeks of age, within 1 week after weaning. In contrast, TCRγδ+ IELs (γδIELs) started producing IFN-γ at 7 weeks of age. In mice lacking Eγ4, an enhancer of the TCRγ locus (Eγ4-/- mice), Thy-1+ Vγ5+ γδIELs, a major subpopulation of γδIELs, were specifically reduced and their ability to produce IFN-γ was severely impaired, whereas Vγ2+ γδIELs normally produced IFN-γ. In Eγ4-/- mice, TCR expression levels were reduced in Vγ5+ γδIEL precursors in the thymus but unchanged in the Vγ5+ IELs. Nevertheless, TCR responsiveness in Vγ5+ γδIELs was impaired in Eγ4-/- mice, suggesting that the TCR signal received in the thymus may determine TCR responsiveness and the ability to produce IFN-γ in the gut. These results suggest that αßIELs and γδIELs start producing IFN-γ at different life stages and that the ability of Vγ5+ γδIELs to produce IFN-γ in the gut may be predetermined by TCR signaling in IEL precursors in the thymus.

Breed-Driven Microbiome Heterogeneity Regulates Intestinal Stem Cell Proliferation via Lactobacillus-Lactate-GPR81 Signaling.

Genetically lean and obese individuals have distinct intestinal microbiota and function. However, the underlying mechanisms of the microbiome heterogeneity and its regulation on epithelial function such as intestinal stem cell (ISC) fate remain unclear. Employing pigs of genetically distinct breeds (obese Meishan and lean Yorkshire), this study reveals transcriptome-wide variations in microbial ecology of the jejunum, characterized by enrichment of active Lactobacillus species, notably the predominant Lactobacillus amylovorus (L. amylovorus), and lactate metabolism network in obese breeds. The L. amylovorus-dominant heterogeneity is paralleled with epithelial functionality difference as reflected by highly expressed GPR81, more proliferative ISCs and activated Wnt/ß-catenin signaling. Experiments using in-house developed porcine jejunal organoids prove that live L. amylovorus and its metabolite lactate promote intestinal organoid growth. Mechanistically, L. amylovorus and lactate activate Wnt/ß-catenin signaling in a GPR81-dependent manner to promote ISC-mediated epithelial proliferation. However, heat-killed L. amylovorus fail to cause these changes. These findings uncover a previously underrepresented role of L. amylovorus in regulating jejunal stem cells via Lactobacillus-lactate-GPR81 axis, a key mechanism bridging breed-driven intestinal microbiome heterogeneity with ISC fate. Thus, results from this study provide new insights into the role of gut microbiome and stem cell interactions in maintaining intestinal homeostasis.

Leiomyosarcoma of the small bowel presenting as an acute small bowel obstruction.

Leiomyosarcoma is a subtype of soft-tissue sarcoma, which is a rare soft-tissue malignancy comprising < 1% of adult cancers. There are a variety of etiologies of small bowel obstruction. Infrequently, small bowel malignancies can first present as small bowel obstruction. In exceedingly rare cases, leiomyosarcomas can be the offending malignancy. A 53-year-old male presented to the emergency department with several weeks of persistent right abdominal pain, nausea, and vomiting. Computed tomography scan revealed a central necrotic mass within the right lower quadrant originating from the small bowel. The patient underwent exploratory laparotomy to relieve the obstruction and a mass was identified originating from the terminal ileum that adhered to surrounding structures. Pathological analysis determined the mass to be small bowel leiomyosarcoma. Leiomyosarcoma is definitively diagnosed after primary resection with histopathology and immunohistochemistry. As opposed to other small bowel neoplasms, surgical resection with negative margins is the only potentially curative option.

Adaptations in Gastrointestinal Nutrient Absorption and its Determinants During Pregnancy in Monogastric Mammals: A Scoping Review.

CONTEXT: Pregnancy increases nutrient demand, but how nutrient uptake and its determinants adapt to facilitate this is unclear. OBJECTIVE: This review aimed to identify and characterize evidence and evidence gaps regarding changes in gastrointestinal nutrient absorption and its determinants during pregnancy in monogastric mammals. DATA SOURCES: A scoping review of peer-reviewed sources was conducted across PubMed, Scopus, Web of Science, Embase, and ProQuest (theses and dissertations) databases. DATA EXTRACTION: Data extracted included species, pregnancy stages and outcomes. Where sufficient data for a given outcome was available, relative values were summarized graphically or in tables, to allow comparison across pregnancy stages and/or small intestine regions. Searches identified 26 855 sources, of which only 159 were eligible. Mechanistic studies were largely restricted to rodents, and most compared non- and late-pregnant groups, with fewer studies including early- or mid-pregnant groups. DATA ANALYSIS: During pregnancy, there is some evidence for greater capacity for glucose uptake but unchanged amino acid uptake, and good evidence for increased uptake of calcium, iron, and zinc, and slower gastrointestinal passage of nutrients. The available evidence indicates that acute glucose uptake, gastric emptying, and the activities of sucrase, maltase, and lactase do not change during pregnancy. Gaps in the knowledge include the effects of pregnancy on uptake of specific amino acids, lipids, and most minerals and vitamins. CONCLUSION: The results indicate that the gastrointestinal tract adapts during pregnancy to facilitate increased nutrient absorption. Additional data is required in order to assess the underlying mechanisms for and impacts on the absorption of many nutrients, as well as to determine the timing of these adaptations.

Detecting emergence of ruptures in individual layers of the stretched intestinal wall using optical coherence elastography: A pilot study.

We report a new application of compression optical coherence elastography (C-OCE) to monitor the emergence of ruptures in individual layers of longitudinally stretched small-intestine walls using tissue samples (n = 36) from nine minipigs. Before stretching, C-OCE successfully estimated stiffness for each intestine-wall layer: longitudinal muscular layer with serosa, circumferential muscular layer, submucosa and mucosa. In stretched samples, C-OCE clearly visualized initial stiffening in both muscular layers. By 25% elongation, a sharp stiffness decrease for the longitudinal muscular layer, indicated emergence of tears in all samples. With further stretching, for most samples, ruptures emerged in the circumferential muscular layer and submucosa, while mucosa remained undamaged. Histology confirmed the OCE-revealed damaging and absence of tissue damage for ~15% elongation. Thus, C-OCE has demonstrated a high potential for determining the safety tissue-stretching threshold which afterward may be used intraoperatively to prevent rupture risk in intestinal tissues stretched during various diagnostic/therapeutic procedures.

The gut microbiota and diabetes: research, translation, and clinical applications - 2023 Diabetes, Diabetes Care, and Diabetologia Expert Forum.

This article summarises the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organised by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: (1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g. genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomisation in humans; (2) the highly individualised nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; (3) because single time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and (4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal.