Low Fecal Calprotectin Predicts Histological Healing in Patients with Ulcerative Colitis with Endoscopic Remission and Leads to Prolonged Clinical Remission.

BACKGROUND: Consensus regarding the cutoff value of fecal calprotectin (FC) for predicting histological healing (HH) in ulcerative colitis (UC) is lacking. This study aimed to determine an optimal FC cutoff value for predicting HH in patients with UC with clinical and endoscopic remission. Furthermore, FC's predictability for prolonged clinical remission (CR) was investigated. METHODS: Patients with UC in clinical and endoscopic remission, defined as a partial Mayo score (PMS) ≤ 2 points and a Mayo endoscopic subscore 0-1, were prospectively enrolled. Biopsy samples were evaluated by Geboes score (GS), with HH defined as a GS < 2.0. Patients were followed for 2 years or until relapse, defined as a PMS > 2 or medication escalation. RESULTS: Seventy-six patients with UC were included. The median FC value in patients with HH (n = 40) was 56.2 µg/g, significantly lower than that in those with histological activity (118.1 µg/g; P < .01). The area under the curve (AUC) in a receiver operating characteristic (ROC) curve analysis to predict HH for FC was 0.71 (95% confidence interval [CI], 0.59-0.83), with an optimal cutoff value of 82.7 µg/g (73% sensitivity; 64% specificity; P < .01). Of 74 patients observed for 2 years, 54 (73%) had prolonged CR. In the ROC curve analysis, the AUC to predict prolonged CR for FC was 0.79 (95% CI, 0.68-0.90), equivalent to that for HH (0.73; 95% CI, 0.64-0.86; P = .40). The optimal FC cutoff value to predict prolonged CR was 84.6 µg/g (72% sensitivity; 85% specificity; P < .01). CONCLUSIONS: Fecal calprotectin < 82 µg/g predicts HH in patients with UC with clinical and endoscopic remission. Low FC leads to prolonged CR, equivalent to HH.

Fecal calprotectin (FC) levels < 82 µg/g predict histological healing in ulcerative colitis patients with clinical and endoscopic remission. Low FC leads to prolonged clinical remission for up to 2 years in those with clinical and endoscopic remission, equivalent to histological healing.

Long-lasting renal dysfunction following tacrolimus induction therapy in ulcerative colitis patients.

Although tacrolimus (TAC) has remarkable effects in ulcerative colitis (UC) patients when given as remission induction therapy, some can develop renal dysfunction during TAC administration, resulting in withdrawal, though related details remain poorly understood. This study was conducted to determine the impact of oral TAC on renal function for remission induction therapy in UC patients. Fifty-five patients (10 elderly, 45 non-elderly) with UC and treated with oral TAC at our hospital were retrospectively evaluated. Renal function was assessed using estimated glomerular filtration rate (eGFR). Although a high clinical response to TAC was seen in both elderly and non-elderly, a decline in eGFR was noted in nearly all patients regardless of age, with a maximum change of -34.4% from the baseline value at week 11. Furthermore, eGFR decline recovered quickly after TAC discontinuation, though did not return to the baseline at two years following cessation. The rate of eGFR change at week 12 was significantly associated with patient age (ß = -0.3242, p = 0.0103) and peak serum trough level during TAC treatment (ß = 0.3563, p = 0.0051). Furthermore, the rate of decline in eGFR was significantly greater during treatment with TAC in the elderly as compared to non-elderly, with a large difference in eGFR decline rate between those groups also noted at two years after withdrawal of treatment. Careful attention to renal function when administering oral TAC for UC is important and changes in eGFR should be monitored closely in elderly patients even after treatment cessation.

The Simultaneous Onset of Pancreatitis and Colitis as Immune-related Adverse Events in a Patient Receiving Nivolumab Treatment for Renal Cell Carcinoma.

Immune checkpoint inhibitors (ICIs), which have anti-tumor effects, are currently approved for treatment of several kinds of advanced malignancies. However, with their increasing use, a variety of immune-related adverse events (irAEs) in administered patients have been reported. We herein report a rare case of the simultaneous onset of acute pancreatitis and colitis as irAEs during nivolumab treatment given to a patient with renal cell carcinoma, who then shown marked improvement with corticosteroid therapy.

Primary Extragastrointestinal Stromal Tumor of Greater Omentum with Intraperitoneal Bleeding.

Gastrointestinal stromal tumors (GISTs) develop in the digestive tract, mainly in the stomach, small intestine, colon, or esophagus. However, primary tumors with the same pathologic features as GISTs have been reported to occur outside of the digestive tract and are called extragastrointestinal stromal tumor (EGIST). We herein report a rare case of EGIST arising from the greater omentum in a patient with abdominal pain caused by intraperitoneal bleeding from the tumor.

Intermittent Purpura Development Associated with Leukocytoclastic Vasculitis Induced by Infliximab for Crohn's Disease.

Anti-tumor necrosis factor (TNF) α agents, widely used for the treatment of Crohn's disease (CD), can sometimes induce skin-associated adverse events, which mainly include psoriasis-like eruptions, eczema, and cutaneous infections. In contrast, purpura caused by vasculitis is rarely seen. We herein report a unique case of leukocytoclastic vasculitis induced by infliximab administered for CD in which intermittent purpura development was noted. Fluorescent immunostaining showed no immunoglobulin A deposition on the vessel walls. No purpura was initially seen after starting infliximab, but it appeared approximately 10 months later; however, administration did not have to be discontinued, and the condition was later resolved. The present findings provide important details regarding vasculitis induced by anti-tumor necrosis factor-α agent administration.

Comorbid irritable bowel syndrome symptoms and headache have greater association with anxiety than depression: Annual health check-up survey results.

High rates of co-existing irritable bowel syndrome (IBS) and headache have been reported in western countries. We investigated that comorbidity in individuals in Japan, along with anxiety and depression in subjects with and without IBS symptoms and/or headache.This cross-sectional study was performed from April 2012 to January 2013 at the Matsue Seikyo General Hospital Health Check Center. Questionnaires concerning symptoms related to IBS (Rome III) and headache, as well as anxiety/depression score were sent to individuals scheduled to undergo an annual health check-up, then returned during the visit and analyzed in a blinded manner.A total of 2885 individuals returned completed questionnaires and were enrolled, of whom 218 (7.6%) met the IBS criteria. The rates of co-existing headache in subjects with and without IBS symptoms were 44.0% (96/218) and 22.9% (611/2667), respectively, indicating a significantly higher rate of co-existing headache in subjects with as compared to without IBS (odds ratio [OR] 2.65, P < .001). Furthermore, the percentage of subjects with anxiety along with comorbid IBS symptoms and headache was significantly greater as compared to those with IBS (OR 3.01, P = .001) or headache (OR 2.41, P < .001) alone. Unlike anxiety, the percentage of subjects with depression was not significantly different among the IBS/non-headache, non-IBS/headache, and IBS/headache groups.Subjects with IBS symptoms had a higher rate of co-existing headache as compared to those without IBS. Furthermore, those with comorbid IBS symptoms and headache had a greater association with anxiety than with depression, as compared to those with only IBS or headache.

Prevalence of functional dyspepsia-like symptoms in ulcerative colitis patients in clinical remission and overlap with irritable bowel syndrome-like symptoms.

Objective: Quiescent ulcerative colitis (UC) patients often have irritable bowel syndrome (IBS)-like symptoms and we recently showed that the prevalence of IBS-like symptoms in UC patients in clinical remission was significantly higher as compared to healthy control subjects. However, the prevalence of functional dyspepsia (FD)-like symptoms in quiescent UC patients remains unknown. The purpose of this study was to evaluate the prevalence of FD-like symptoms and the overlap with IBS-like symptoms in such patients.Materials and Methods: We reanalyzed the records of UC patients in remission using the subject cohort from our previous study. Clinical remission was defined as a clinical activity index (CAI) value ≤4 for at least 6 months. Diagnoses of FD- and IBS-like symptoms were evaluated by questionnaire according to the Rome III criteria.Results: One hundred seventy-two UC patients in clinical remission and 330 healthy control subjects were analyzed. Of the 172 patients, 9 (5.2%) met the criteria of FD, which was comparable with the controls (22/330, 6.7%). The prevalence rate of FD-like symptoms in UC patients with IBS-like symptoms (7/46, 15.2%) was lower as compared to that of the control subjects (6/16, 37.5%). On the other hand, a high percentage of the UC patients with FD-like symptoms also had IBS-like symptoms (7/9, 77.8%).Conclusions: Although the prevalence of FD-like symptoms in quiescent UC patients with IBS-like symptoms was low, UC patients with FD-like symptoms frequently had IBS-like symptoms.

A case of insulin-like growth factor 2-producing gastrointestinal stromal tumor with severe hypoglycemia.

BACKGROUND: Non-islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome that secretes incompletely processed high molecular weight insulin growth factor 2 (big-IGF2), which results in stimulation of the insulin receptor and subsequently induces hypoglycemia. Gastrointestinal stromal tumor (GIST) is a common intestinal mesenchymal neoplasm of the gastrointestinal tract. The most frequent site of GIST is the stomach; NICTH induced by IGF2-producing stomach GISTs is rare. CASE PRESENTATION: An 84-year-old man was admitted to the hospital due to impaired consciousness (JCS II-10) in the morning. At the time of admission, his serum glucose was 44 mg/dL; his consciousness was restored with 20 ml of 50% glucose. To avoid hypoglycemia, a continuous intravenous infusion of glucose as well as dietary intervention was required. At the time of hypoglycemia, the levels of insulin and C-peptide were suppressed. Additionally, IGF1 levels were below the normal range. Abdominal computed tomography revealed that he had a large lobulated mass (116 × 70 × 72 mm) around the gastric corpus. Pathological analysis of biopsy specimens identified disarray of spindle cells and positivity for c-kit as well as strong positivity for DOG-1. Further analysis revealed high levels of Ki-67 (Mib-1 index: 15.5%) and mitotic index (7/50HPF); the tumor was diagnosed as high-risk GIST, and complete surgical resection was performed. Hypoglycemia resolved immediately after tumor resection. The resected tumor specimen was positive for IGF2 staining, and big-IGF2 (11-18 kDa) was detected in preoperative serum and tumor samples; the patient was diagnosed with NICTH due to an IGF2-producing tumor. CONCLUSIONS: NICTH is rare in GIST of the stomach; however, the large GIST could produce big-IGF2 and subsequently cause severe hypoglycemia, requiring prompt evaluation and complete tumor resection.

Gossypiboma penetrating into the small intestine similar to Meckel's diverticulum: a report and literature review.

Foreign body granuloma due to retained surgical sponge (gossypiboma) with penetration into the small intestine is very rare. Cases of gossypiboma in the abdominal cavity have sometimes been reported, yet the correct incidence has not been determined, only estimated to occur in one of every 1,000 to 1,500 intra-abdominal operations. Acute abdomen may be observed in some cases, requiring treatment. We herein introduce the case of a 70-year-old woman with gossypiboma penetrating into the small intestine presented with anemia and hematochezia. She had a history of emergency laparotomy for ectopic pregnancy several decades ago. A dynamic contrast-enhanced computed tomography revealed a hypovascular mass containing air bubbles that continued to the small intestine approximately 50 mm in size in the right lower abdomen. In addition to describing the presentation and outcome of our patient, we review the image findings of gossypiboma.

Interleukin-33 delays recovery of mucosal inflammation via downregulation of homeostatic ABCG5/8 in the colon.

Previous studies have suggested that interleukin-33 (IL-33) is involved in the pathogenesis of ulcerative colitis (UC), though the detailed mechanisms are not fully known. We investigated IL-33-mediated colonic homeostasis using a mechanistic method. Il33-/- mice were more tolerant to dextran sulfate sodium-induced acute colitis than the wild type and also showed delayed recovery from colitis with recombinant IL-33 (rIL-33) administration. Unexpectedly, microarray analysis identified significant downregulation of the Abcg5/8 genes in mouse colons following rIL-33 treatment. ABCG5/8 are known cholesterol transporters in the small intestine and liver, though their colon activities have not been elucidated, thus their role in IL-33-mediated inflammation was investigated. In vitro, toll-like receptor (TLR) stimulation upregulated ABCG5/8 mRNA expression in Caco2 and HCT-15 cells, with subsequent downregulation by rIL-33, while inhibition of ABCG5/8 along with their siRNA increased TLR-stimulated IL-8 production. Together, these results indicated that colonic ABCG5/8 play a regulatory role in TLR-induced inflammation, while histological inflammation in human UC was correlated positively with the level of mucosal IL-33 and inversely with that of colonic ABCG5/8. This is the first report of IL-33-mediated downregulation of colonic ABCG5/8 in a colitis recovery phase, indicating their involvement in UC pathogenesis and potential as a therapeutic target.

Eosinophilic Granulomatosis with Polyangiitis Initially Diagnosed as Eosinophilic Gastroenteritis.

We herein report two cases of eosinophilic granulomatosis with polyangiitis (EGPA) initially diagnosed as eosinophilic gastroenteritis (EGE) based solely on endoscopic biopsy results. One year after the EGE diagnosis, one patient presented with multiple purpura, and skin biopsy findings resulted in a change of the diagnosis to EGPA. In another patient, multiple skin and colonic ulcerations emerged eight years after the diagnosis of EGE, at which time histological examinations of endoscopic biopsy specimens revealed vasculitis, and the diagnosis was changed to EGPA. Physicians should be aware of the possible existence of EGPA in cases diagnosed as EGE.

Ten-year follow-up study of linear immunoglobulin A dermatosis complicated with ulcerative colitis.

Linear immunoglobulin A dermatosis (LAD) is rarely complicated in patients with ulcerative colitis (UC), though the long-term prognosis in those with concurrent LAD and UC is not fully understood. Here, we report findings obtained in follow-up examinations performed over a 10-year period of a UC patient initially complicated with LAD. We treated an 18-year-old male for relapse of UC with deteriorating blisters diagnosed as LAD. Following successful induction therapy for both UC and LAD with oral prednisolone, the patient was followed for 10 years. Skin condition remained good at each examination, even with second and third relapses of UC. Our findings in this case indicate that LAD is rarely complicated with UC, while it has no association with colitis disease activity. Furthermore, adequate treatment following an initial diagnosis of LAD is important for management of affected UC patients.

Sigmoid endometriosis diagnosed preoperatively using endoscopic ultrasound-guided fine-needle aspiration.

We report a case of sigmoid endometriosis diagnosed preoperatively based on endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) findings. A 42-year-old female came to us with left lower abdominal pain and bloating that had started 3 months prior. CT and MRI results showed wall thickening of the sigmoid colon. A colonoscopy procedure could not be completed because passage through the sigmoid colon was blocked due to severe stenosis, while mucosal biopsy samples obtained during that procedure could not confirm a diagnosis. EUS-FNA was then performed and specimens were obtained from the muscular layer with stenosis, which revealed a thickened hypoechoic lesion. Histological findings obtained by use of EUS-FNA demonstrated a large amount of fibrosis in endometrial glands and a diagnosis of sigmoid endometriosis was confirmed by additional immunostaining. Thus, a laparoscopic sigmoidectomy was performed, with sigmoid endometriosis finally diagnosed. Confirmation of a diagnosis of intestinal endometriosis based on histological findings of mucosal biopsy specimens obtained by colonoscopy is difficult, because endometrial implants are primarily located in the serosal and/or muscular layer. When safe aspiration is possible, we consider that EUS-FNA can be an effective method for preoperative diagnosis of intestinal endometriosis, which may contribute to avoidance of unnecessary or excessive surgery.

Retained Rice Cake: A Unique Upper Gastrointestinal Foreign Body: Case Report and a Literature Review.

As a rarely recognized foreign body in the upper gastrointestinal tract, rice cake frequently requires endoscopic removal. We herein report six patients with characteristic sonography, computed tomography (CT), spectroscopy, endoscopy, and histological findings. A review of all published cases, including ours, revealed that retained rice cake in the stomach typically shows the following: abdominal pain (93.3%), mucosal injury (93.3%) with bleeding (42.9%); high-density (120-206 Hounsfield units) CT findings; and indication for endoscopy (80%). In the esophagus, hot, toasted rice cake causes thermal injury. Primary physicians should be aware of this popular-food-induced, but rare, disorder.

Capabilities of fecal calprotectin and blood biomarkers as surrogate endoscopic markers according to ulcerative colitis disease type.

Fecal calprotectin level in ulcerative colitis patients is correlated with endoscopic findings. However, its association with various ulcerative colitis disease types has not been elucidated. In the present study, we investigated the correlation of fecal calprotectin level with endoscopic findings as compared to blood biomarkers according to ulcerative colitis disease type. Fecal calprotectin as well as the blood biomarkers: C-reactive protein (CRP), white blood count (WBC), erythrocyte sedimentation rate (ESR), hemoglobin, platelet count (PLT), and serum albumin (Alb) were measured in patients who underwent a complete colonoscopy. Disease type was divided into proctitis, left-sided colitis, and extensive colitis. Correlations of fecal calprotectin and blood biomarker levels with Mayo endoscopic subscore were analyzed. A total of 186 colonoscopy examinations were performed in 124 patients with ulcerative colitis. Fecal calprotectin level showed a significant correlation with Mayo endoscopic subscore regardless of disease type (proctitis, r = 0.54, p<0.01; left-sided colitis, r = 0.75, p<0.01; extensive colitis, r = 0.78, p<0.01), and clearly discriminated inactive (Mayo endoscopic subscore 0) from active stages (Mayo endoscopic subscore 1-3). On the other hand, none of the examined blood biomarkers showed a correlation with Mayo endoscopic subscore in the proctitis group, while weak correlations of several biomarkers (CRP, WBC, ESR, PLT and Alb) with Mayo endoscopic subscore were found in left-sided colitis and extensive colitis cases. This is the first report to elucidate the capabilities of fecal calprotectin and blood biomarkers as endoscopic surrogate markers according to ulcerative colitis disease type.

Successful Food-Elimination Diet in an Adult with Eosinophilic Gastroenteritis.

We successfully treated a 22-year-old woman with eosinophilic gastroenteritis (EGE) using a multiple food-elimination diet. The patient was diagnosed with EGE based on histopathological findings and initially treated with oral prednisolone. The symptoms immediately improved, although they recurred when prednisolone was tapered to a low dose. We then treated her with a multiple food-elimination diet, including milk, soy, eggs, wheat, nuts, seafood, and rice. During dietary treatment, we identified dairy products and eggs as causative foods of the symptoms, and we ceased prednisolone. Similar to eosinophilic esophagitis, an elimination diet may be effective for adult patients with EGE.

Correction to: Postoperative recurrence from tract seeding after use of EUS-FNA for preoperative diagnosis of cancer in pancreatic tail.

The correct name of the corresponding author should be ''Nobuhiko Fukuba'', and not ''Nobuhiko Fukuban'' as given in the original publication of the article.

Postoperative recurrence from tract seeding after use of EUS-FNA for preoperative diagnosis of cancer in pancreatic tail.

A 50-year-old male underwent abdominal computed tomography at a city hospital in Japan, which revealed a tumor 38 mm in diameter in the tail of the pancreas. Based on findings from endoscopic ultrasonography-guided fine needle aspiration using a 22-gauge needle with a side hole, the tumor was diagnosed as an invasive ductal carcinoma. The patient was referred to our hospital and underwent a distal pancreatectomy. Esophagogastroduodenoscopy performed as part of a medical checkup at another hospital 2 years later revealed a 20-mm-sized submucosal tumor in the posterior wall of the upper body of the stomach. Examination of a biopsy specimen obtained from the top of the lesion revealed adenocarcinoma. Partial resection of the stomach was performed and pathological findings showed an adenocarcinoma in all layers of the stomach wall, consistent with recurrence derived from needle tract seeding of the previously excised cancerous tumor from the pancreatic tail. Additional experimentation performed for confirmation with an agar model showed that agar on the deep side leaked to the shallow side following puncture with a needle with a side hole used with a slow-pull technique.

Serum amyloid A level correlated with endoscopic findings in patients with Crohn's disease-Possible biomarker for evaluating mucosal healing.

BACKGROUND: Mucosal healing (MH) has been proposed as an essential therapeutic goal for treatment of Crohn's disease (CD) patients. The utility of serum amyloid A (SAA) for prediction of MH in CD patients is lacking. AIMS: This study was conducted to evaluate the correlation of SAA with CD-related endoscopic disease activity. METHODS: SAA levels in serum samples obtained from CD patients as well as endoscopic findings based on a simple endoscopic score for CD (SES-CD) were assessed in relation to CD activity index (CDAI). The diagnostic ability of MH in correlation with SAA level was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Fifty-five patients with CD were enrolled. Mean SAA level was significantly higher in clinical and endoscopic active phases as compared to an inactive phase. SAA level was also significantly correlated with SES-CD (r = 0.64, p < 0.01) and CDAI (r = 0.42, p < 0.01). The area under the ROC curve for SAA level was 0.77 and the optimal cut-off value for SAA to predict MH was 5.9 µg/dl. SAA level was shown to be associated with MH, with a sensitivity of 68% and specificity of 83%. CONCLUSIONS: SAA may be a possible biomarker for evaluating MH in CD patients.

Fecal Calprotectin More Accurately Predicts Endoscopic Remission of Crohn's Disease than Serological Biomarkers Evaluated Using Balloon-assisted Enteroscopy.

BACKGROUND: Fecal calprotectin (FC) has emerged as a reliable surrogate marker of endoscopic remission in Crohn's disease (CD), which has been mainly evaluated using ileocolonoscopy. We conducted this study to clarify the predictability of FC level for predicting endoscopic remission using balloon-assisted enteroscopy (BAE) findings in patients with CD and compare with that of conventional serological biomarkers. METHODS: Patients with CD scheduled to undergo BAE were prospectively enrolled, and fecal and blood samples collected before the procedures. We used a modified simple endoscopic score for CD, in which the parameter "presence of narrowing" was removed from conventional simple endoscopic score for CD. Endoscopic remission was defined as modified simple endoscopic score for CD 0 to 2. RESULTS: Seventy BAE procedures were performed in 53 patients with CD and evaluated. The area under the curve in receiver operating characteristic curve analysis of FC to predict endoscopic remission was 0.93, with an optimal cut-off value of 252.9 µg/g, and 96% sensitivity and 83% specificity, which was higher than that for C-reactive protein, albumin, white blood cell count, and platelet count (0.76, 0.66, 0.39, and 0.65, respectively). The area under the curve of FC for predicting endoscopic remission was high in patients with ileal and ileocolonic disease location (0.86 and 0.96, cut-off values 204.2 and 253.7 µg/g, respectively), and also higher than the area under the curve values of serological markers. CONCLUSIONS: BAE findings showed that FC was more accurate for predicting endoscopic remission in CD than C-reactive protein, albumin, white blood cell count, and platelet count. Even in small-bowel CD, FC may be a more reliable surrogate marker of endoscopic remission than serological biomarkers.