Mass-forming immunoglobulin G4-related cholangitis with atypical pancreatic lesions: a case report of difficult diagnosis.

BACKGROUND: Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a systemic immune-mediated fibroinflammatory disease that results in the tissue destruction of multiple organs. IgG4-RD is often underdiagnosed or misdiagnosed as malignant, infectious, or other inflammatory disorder. CASE PRESENTATION: We describe a 56-year-old woman presented with jaundice and weight loss. Radiological imaging showed common hepatic duct wall thickening and nodular lesions in the pancreas, which was highly suspicious of malignancy. However, she was contraindicated for biopsy; hence, the diagnosis of IgG4-RD was made based on her high serum IgG4 level, multiorgan involvement, and steroid response. The effect of steroid therapy was significant, although the disease relapsed during the maintenance treatment. The dosage of steroid was re-increased, and the patient was under close follow-up. CONCLUSIONS: The diagnosis of IgG4-RD is challenging due to its diverse manifestations. Therefore, a careful systematic assessment is necessary to improve the accuracy of IgG4-RD diagnosis, and a close follow-up is important to monitor the disease development as well as adjust the treatment strategy accordingly.

Systemic immunoglobulin light chain (AL) amyloidosis initially presenting as hematochezia: a case report.

BACKGROUND: Amyloidosis, an systemic disorder featuring an accumulation of misfolded proteins, is a significant diagnostic challenge because of its broad range of symptoms. The symptoms of amyloidosis vary depending on the affected organs. Amyloid accumulation in the kidney generally manifests as proteinuria or impaired kidney function, whereas cases with gastrointestinal (GI) involvement present as abdominal pain, weight loss, or GI bleeding. CASE DESCRIPTION: We report a case of systemic immunoglobulin light chain (AL) amyloidosis involving the colon and kidney in a 75­year­old female who presented with intermittent lower abdominal pain and hematochezia. A colonoscopy revealed multiple ulcerations and a submucosal hematoma with κ light chain deposition confirmed by biopsy. The patient had many comorbidities, including renal tuberculosis, chronic kidney disease, diabetes, coronary heart disease (CHD), and paroxysmal atrial fibrillation, which rendered her clinical manifestations confusing. Her condition was relatively stable during treatment with bortezomib and dexamethasone for 4 cycles. CONCLUSIONS: Systemic amyloidosis usually has a poor prognosis since most cases are detected in the late disease phase. Early disease detection depends on a comprehensive understanding of the disease and a keen recognition of the lesion. We suggest that in patients with hematochezia, colonic ulcer, and submucosa hematoma, amyloidosis with colonic involvement should be considered when other diseases are excluded.

CYP24A1 Involvement in Inflammatory Factor Regulation Occurs via the Wnt Signaling Pathway.

OBJECTIVE: While the upregulation of cytochrome P450 family 24 subfamily A member 1 (CYP24A1) gene expression has been reported in colon cancer, its role in tumorigenesis remains largely unknown. In this study, we aimed to investigate the involvement of CYP24A1 in Wnt pathway regulation via the nuclear factor kappa B (NF-κB) pathway. METHODS: The human colon cancer cell lines HCT-116 and Caco-2 were subjected to stimulation with interleukin-6 (IL-6) as well as tumor necrosis factor alpha (TNF-α), with subsequent treatment using the NF-κB pathway-specific inhibitor ammonium pyrrolidinedithiocarbamate (PDTC). Furthermore, CYP24A1 expression was subjected to knockdown via the use of small interfering RNA (siRNA). Subsequently, NF-κB pathway activation was determined by an electrophoretic mobility shift assay, and the transcriptional activity of ß-catenin was determined by a dual-luciferase reporter assay. A mouse ulcerative colitis (UC)-associated carcinogenesis model was established, wherein TNF-α and the NF-κB pathway were blocked by anti-TNF-α monoclonal antibody and NF-κB antisense oligonucleotides, respectively. Then the tumor size and protein level of CYP24A1 were determined. RESULTS: IL-6 and TNF-α upregulated CYP24A1 expression and activated the NF-κB pathway in colon cancer cells. PDTC significantly inhibited this increase in CYP24A1 expression. Additionally, knockdown of CYP24A1 expression by siRNA could partially antagonize Wnt pathway activation. Upregulated CYP24A1 expression was observed in the colonic epithelial cells of UC-associated carcinoma mouse models. Anti-TNF-α monoclonal antibody and NF-κB antisense oligonucleotides decreased the tumor size and suppressed CYP24A1 expression. CONCLUSION: Taken together, this study suggests that inflammatory factors may increase CYP24A1 expression via NF-κB pathway activation, which in turn stimulates Wnt signaling.

High-grade B-cell lymphoma with gastroduodenal involvement showing paraneoplastic cerebellar degeneration: a case report.

Background: Paraneoplastic cerebellar degeneration (PCD), which displays ataxia and other cerebellar symptoms, is the most common paraneoplastic neurological syndrome (PNS). PCD is more likely to occur in individuals with small cell lung cancer (SCLC), gynecological malignancies, and Hodgkin disease, but it is rarely associated with non-Hodgkin lymphoma (NHL). Case Description: We report a case of PCD accompanying high-grade B-cell lymphoma embedded in an individual's stomach and duodenum, who also presented with acute onset of gait ataxia and slurred speech. The results of the common laboratory tests for neurological disorders, including the paraneoplastic antibody test, were negative. The key to the accurate diagnosis was the positron emission tomography/computed tomography findings. The final diagnosis of high-grade B-cell lymphoma was unclear until the performance of repeated esophagogastroscopy with multipoint deep excavation biopsies. After standard chemotherapy, the patient's gastric tumor was significantly alleviated and cerebellar syndrome was significantly improved. Conclusions: This case highlights the challenges of diagnosing PNS associated with occult malignancy. PNS patients may present with a variety of neurological disorders; Thus, if any unexplained neurological symptoms appear after a series of specific laboratory and imaging tests, a diagnosis of PNS should be taken into consideration in the differential diagnosis list, as it may help clinicians identify asymptomatic malignancies and ensure patients receive correct treatments in a timely manner. A high-quality endoscopic biopsy is essential, as it helps hematologists make an accurate diagnosis of lymphoma with gastroduodenal involvement based on pathology.

Effects and mechanism of the bile acid (farnesoid X) receptor on the Wnt/ß-catenin signaling pathway in colon cancer.

The downregulation of farnesoid X receptor (FXR; gene name, nuclear receptor subfamily 1 group h member 4), an enteric nuclear bile acid receptor, has been reported in colorectal carcinoma (CRC), and FXR expression has been inversely correlated with CRC stage and clinical outcome. FXR knockdown in chronic colitis mouse models of intestinal tumorigenesis results in early mortality and increased tumor progression via promoting Wnt signaling. The aim of the present study was to explore the effects and mechanism of FXR on the Wnt/ß-catenin signal pathway in CRC. FXR and ß-catenin protein expression levels were detected in an ulcerative colitis mouse model and human colon cancer cell lines (HT-29, Caco-2 and HCT-116). Gain- and loss-of-function studies were conducted by transfecting colon cancer cells with FXR siRNA and treating them with the FXR agonist GW4064. Subsequently, ß-catenin transcriptional activity was measured using the dual-luciferase assay, and ß-catenin/TCF4 complex levels and ß-catenin protein and mRNA expression levels were determined. FXR and ß-catenin expression levels were inversely associated in both the animal model and colon cancer cells. The Wnt signaling pathway was activated by increased ß-catenin/TCF4 complex levels upon FXR silencing; however, mRNA and protein levels of ß-catenin were not significantly affected. The FXR agonist GW4064 significantly inhibited the proliferation of cells but promoted the transcriptional activity of ß-catenin. Thus, the present study demonstrated that FXR influences the Wnt/ß-catenin signaling pathway. Furthermore, loss of FXR expression promotes the transcriptional activity of ß-catenin, whereas FXR activation results in the opposite effect.

Saccharomyces boulardii alleviates ulcerative colitis carcinogenesis in mice by reducing TNF-α and IL-6 levels and functions and by rebalancing intestinal microbiota.

BACKGROUND AND AIMS: To explore the inhibition mechanism of Saccharomyces boulardii (S. boulardii) on ulcerative colitis (UC) carcinogenesis. METHODS: C57BL/6 mice were treated with azoxymethane and dextran sulfate sodium (AOM/DSS) to develop a UC carcinogenesis model. The treatment group was lavaged with S. boulardii (5 × 107 CFU/d) for 12 weeks. The mice were sacrificed and the tumor load in the treatment group was compared with that of a control group. The levels of TNF-α and IL-6 in colon tissue were measured by enzyme-linked immunosorbent assays. The influence of S. boulardii on TNF-α and IL-6 regulation was also investigated using different colon cell lines. Differences in intestinal microbiota in both stool and intestinal mucosa samples were assessed using 16S rDNA sequencing. RESULTS: S. boulardii treatment reduced AOM/DSS-induced UC carcinogenesis in mice, as indicated by the reduced tumor load and reduced TNF-α and IL-6 levels in vivo, as well its effects on TNF-α and IL-6 activities in vitro. Significant changes in both fecal and mucosal microbiota were observed among the control, the AOM/DSS treated, and AOM/DSS plus S. boulardii treated groups. For fecal microbiota, the AOM/DSS treated group was lower in Lactobacillus, but higher in Oscillibacter and Lachnoclostridium than the control group. After intervention with S. boulardii, the percentage of Bacillus and Lactococcus increased, but Lachnoclostridium, Oscillibacter, Bacteroides, and Pseudomonas decreased. For the intestinal mucosal microbiota, the AOM/DSS treated group was lower in Bifidobacterium and Ruminococcaceae_UCG-014 and higher in Alloprevotella than the control group. After S. boulardii exposure, the percentage contributions of Lachnoclostridium and Lachnospiraceae_NK4A136 increased. CONCLUSIONS: S. boulardii effectively reduced UC carcinogenesis in an AOM/DSS induced mice model. This positive result can likely be attributed to the reduction of TNF-α and IL-6 levels or the blockade of their function combined with alterations to the intestinal microbiota.

VSL#3 can prevent ulcerative colitis-associated carcinogenesis in mice.

AIM: To investigate the effects of VSL#3 on tumor formation, and fecal and intestinal mucosal microbiota in azoxymethane/dextran sulfate sodium (AOM/DSS) induced mice model. METHODS: C57BL/6 mice were administered AOM/DSS to develop the ulcerative colitis (UC) carcinogenesis model. Mice were treated with 5-ASA (75 mg/kg/d), VSL#3 (1.5 × 109 CFU/d), or 5-ASA combined with VSL#3 by gavage from the day of AOM injection for three months (five days/week). The tumor load was compared in each group, and tumor necrosis factor (TNF-α) and interleukin (IL)-6 levels were evaluated in colon tissue. The stool and intestinal mucosa samples were collected to analyze the differences in the intestinal microbiota by 16s rDNA sequencing method. RESULTS: VSL#3 significantly reduced the tumor load in AOM/DSS-induced mice model and decreased the level of TNF-α and IL-6 in colon tissue. The model group had a lower level of Lactobacillus and higher level of Oscillibacter and Lachnoclostridium in fecal microbiota than the control group. After the intervention with 5-ASA and VSL#3, Bacillus and Lactococcus were increased, while Lachnoclostridium and Oscillibacter were reduced. 5-ASA combined with VSL#3 increased the Lactobacillus and decreased the Oscillibacter. The intestinal mucosal microbiota analysis showed a lower level of Bifidobacterium and Ruminococcaceae_UCG-014 and higher level of Alloprevotella in the model group as compared to the control group. After supplementation with VSL#3, Bifidobacterium was increased. 5-ASA combined with VSL#3 increased the level of both Lachnoclostridium and Bifidobacterium. CONCLUSION: VSL#3 can prevent UC-associated carcinogenesis in mice, reduce the colonic mucosal inflammation levels, and rebalance the fecal and mucosal intestinal microbiota.

Clinical,Endoscopic,and Pathologic Features of 36 Patients with Gastric Neuroendocrine Neoplasms.

Objective To explore the clinical features of gastric neuroendocrine neoplasms (GNENs). Methods A total of 36 patients with GNENs who were diagnosed between October 2005 and October 2015 at Peking Union Medical College Hospital were retrospectively analyzed. The demographic characteristics,clinical manifestations,endoscopic findings,and pathologic features as well as the treatments of GNENs were collected and analyzed. Results The average age of 36 patients was (55.8±11.1) years and the male to female ratio was 0.89:1. The clinical manifestations varied,in which abdominal pain was as high as 42.9%. Also,63.9% of the lesions were distributed in the gastric body. The endoscopic appearance of GNENs included polypoid lesions,ulcerative lesions,and mucosal depression. Polypoid lesions were most common,and 73.9% of these polyps were single,with an average diameter of less than 10 mm. Pathological grading included G1-G3 level,while G1 level accounted for 55.6%. Up to 65.2% of patients who undergone gastric body biopsy had pathologic evidence of mucosa atrophy or metaplasia. Therapeutic modalities included endoscopic intervention and surgical resection. Conclusion Patients with GNENs lack specific symptoms. The most common endoscopic appearance is polypoid lesions,mainly in gastric body. Clinicians should be aware of the possibility of GNENs in the polypoid lesions,particularly for those accompanied with gastric body atrophy.