Efficacy of intraoperative fluorescence imaging using indocyanine green-containing gauze in identifying the appropriate dissection layer in laparoscopic intersphincteric resection: A case report.

In laparoscopic intersphincteric resection, identifying the dissection layer near the anus is often difficult. We safely proceeded with it, using indocyanine green-containing gauze on the anal side to remove the internal anal sphincter with indocyanine green fluorography.

Living-Donor Kidney Transplantation With Laparoscopic Nephrectomy From a Donor With Horseshoe Kidney: A Case Report.

BACKGROUND: In living-donor kidney transplantation, laparoscopic nephrectomy from a donor has become widespread. However, more careful treatment is required for nephrectomy from a donor with horseshoe kidney. This report presents an interesting surgical case of laparoscopic nephrectomy from a donor with horseshoe kidney. CASE PRESENTATION: A woman aged 53 years was a donor candidate for living-donor kidney transplantation for her husband. She had no medical history and had no problems on preoperative examination, but contrast-enhanced computed tomography revealed that she had horseshoe kidney. As the isthmus was thin and the contrast effect was poor, the isthmus was considered to have poor kidney parenchyma and consisted almost exclusively of fibrous tissue. Therefore, laparoscopic nephrectomy was performed for the donor. On the basis of the 99m Tc-dimercaptosuccinic acid renal scintigraphy results, the right kidney was collected. A laparoscopic nephrectomy with a retroperitoneal approach was performed using GelPort access platforms in a right abdominal incision with an accessory port. We firmly expanded the isthmus and then dissected it just above the aorta using a linear stapling device. Subsequently, we sutured a renal artery and vein with linear stapling devices. The recipient's surgery was also performed without any problems, and the postoperative course of both donor and recipient was good. CONCLUSIONS: We suggest that even if the donor has horseshoe kidney, laparoscopic donor nephrectomy should be actively considered depending on the thickness of the isthmus of the horseshoe kidney.

Prediction of Recurrence in Patients with Stage III Colon Cancer Using Conventional Clinicopathological Factors and Peripheral Blood Test Data: A New Analysis with Artificial Intelligence.

BACKGROUND: Survival rate may be predicted by tumor-node-metastasis staging systems in colon cancer. In clinical practice, about 20 to 30 clinicopathological factors and blood test data have been used. Various predictive factors for recurrence have been advocated; however, the interactions are complex and remain to be established. We used artificial intelligence (AI) to examine predictive factors related to recurrence. METHODS: The study group comprised 217 patients who underwent curative surgery for stage III colon cancer. Using a self-organizing map (SOM), an AI-based method, patients with only 23 clinicopathological factors, patients with 23 clinicopathological factors and 34 of preoperative blood test data (pre-data), and those with 23 clinicopathological factors and 31 of postoperative blood test data (post-data) were classified into several clusters with various rates of recurrence. RESULTS: When only clinicopathological factors were used, the percentage of T4b disease, the percentage of N2 disease, and the number of metastatic lymph nodes were significantly higher in a cluster with a higher rate of recurrence. When clinicopathological factors and pre-data were used, three described pathological factors and the serum C-reactive protein (CRP) levels were significantly higher and the serum total protein (TP) levels, serum albumin levels, and the percentage of lymphocytes were significantly lower in a cluster with a higher rate of recurrence. When clinicopathological factors and post-data were used, three described pathological factors, serum CRP levels, and serum carcinoembryonic antigen levels were significantly higher and serum TP levels, serum albumin levels, and the percentage of lymphocytes were significantly lower in a cluster with a higher rate of recurrence. CONCLUSIONS: This AI-based analysis extracted several risk factors for recurrence from more than 50 pathological and blood test factors before and after surgery separately. This analysis may predict the risk of recurrence of a new patient by confirming which clusters this patient belongs to.

[Bevacizumab plus UFT Regimen for Four Patients with Stage â £ Colorectal Cancer Receiving Hemodialysis].

We present case reports of 4 patients on hemodialysis with Stage Ⅳ colorectal cancer who received regular dose bevacizumab( twice per week)plus a daily dose of UFT chemotherapy. This regimen was safe and effective in the long-term for these patients without requiring changes in the hemodialysis schedule. The 4 patients were 71, 75, 67, and 66-year-old men who received bevacizumab 32, 49, 22, and 63(ongoing)times, respectively. Progression-free survivalwas 16, 28, 15, and 30 months, respectively; no severe side effects occurred during this therapy. It is possible that the bevacizumab plus UFT regimen may be acceptable in patients with Stage Ⅳ colorectal cancer receiving hemodialysis.

Safety of Direct-Acting Antiviral Therapy for Renal Function in Post-Kidney Transplant Patients Infected with Hepatitis C Virus and a 100% 12-Week Sustained Virologic Response: A Single-Center Study.

Treatment of chronic hepatitis C infection after renal transplantation has been controversial due to the high rate of graft rejections with interferon (IFN)-based therapies. The aim of this study is to review our experience of direct acting antiviral therapy for the recipients of renal transplantation. Eleven recipients who were hepatitis C virus-polymerase chain reaction (PCR) positive were eligible for the treatment with direct acting antivirals. Six recipients were treated with sofosbuvir and ledipasvir, three were treated with elbasvir and grazoprevir, and one was treated with sofosbuvir and ribavirin for 12 weeks. One recipient was treated with glecaprevir and pibrentasvir for 8 weeks. All of the 11 recipients exhibited sustained virologic response at week 12 after the end of treatment. Adverse events were scarce including the two recipients who switched to tacrolimus from cyclosporine at the beginning of the treatment. The direct acting antiviral therapy including new agents appears to be safe and highly efficacious for the recipients after renal transplantation.

Computer-Aided Prediction of Long-Term Prognosis of Patients with Ulcerative Colitis after Cytoapheresis Therapy.

Cytoapheresis (CAP) therapy is widely used in ulcerative colitis (UC) patients with moderate to severe activity in Japan. The aim of this study is to predict the need of operation after CAP therapy of UC patients on an individual level using an artificial neural network system (ANN). Ninety UC patients with moderate to severe activity were treated with CAP. Data on the patients' demographics, medication, clinical activity index (CAI) and efficacy of CAP were collected. Clinical data were divided into training data group and validation data group and analyzed using ANN to predict individual outcomes. The sensitivity and specificity of predictive expression by ANN were 0.96 and 0.97, respectively. Events of admission, operation, and use of immunomodulator, and efficacy of CAP were significantly correlated to the outcome. Requirement of operation after CAP therapy was successfully predicted by using ANN. This newly established ANN strategy would be used as powerful support of physicians in the clinical practice.

Right versus left retroperitoneoscopic living-donor nephrectomy.

PURPOSE: To compare the safety and efficacy of right-side and left-side retroperitoneoscopic donor nephrectomy (RDN) using our hybrid technique. METHODS: We retrospectively reviewed the data obtained from 151 consecutive patients who underwent RDN between May 2005 and July 2013. Right and left nephrectomies were performed in 87 and 64 patients, respectively. We compared these two groups with respect to donors' intraoperative parameters, postoperative outcomes, and recipients' outcomes. RESULTS: There were no significant differences between the two groups regarding donor blood loss, warm ischemia time, donor postoperative creatinine levels, donor postoperative length of hospital stay, recipient creatinine levels at 1 year after transplantation, and 1-year graft survival rate after transplantation. The time required for graft extraction and overall operative time were significantly shorter in the right RDN group than in the left RDN group (152 vs. 168 min, P = 0.016; 175 vs. 195 min, P = 0.0059). Only one case in the right nephrectomy group required open conversion because of uncontrollable bleeding from the inferior vena cava. CONCLUSION: Although larger sample sizes would be required to evaluate postoperative complication rate, these results indicate that both the right and left RDN could be performed with similar donor and recipient outcomes.

Risk and management of intra-abdominal abscess in Crohn's disease treated with infliximab.

BACKGROUND AND AIMS: Infliximab (IFX) is a monoclonal antibody used to treat patients with Crohn's disease (CD). Intra-abdominal abscess formation is a major complication of CD with negative effects on patient prognosis. We have analyzed risk factors for abscess formation in CD patients treated with IFX. METHODS: CD patients who received IFX between January 2000 and April 2011 at Keio University Hospital were analyzed retrospectively. Risk factors for abscess formation were assessed by univariate and multivariate logistic regression analyses. RESULTS: Intra-abdominal abscess was seen in 15 of 258 patients. Univariate analyses showed serum C-reactive protein (CRP) concentration at 14 weeks after initiation of IFX (p = 0.021), serum albumin concentration at week 0 (p = 0.022) and week 14 (p = 0.004), the presence of anal lesions (p = 0.036), progression of intestine deformation (p = 0.015) and early loss of response to IFX (p < 0.0001) to be risk factors. Multivariate analysis showed that CRP concentration at 14 weeks [odds ratio (OR) 1.361] and loss of IFX response within 6 months (OR 5.361) were independent risk factors. CONCLUSIONS: Abscess formation should be suspected in patients with symptoms of CD recurrence during IFX therapy. Uncontrolled CRP concentration and early loss of response to IFX are risk factors.

The 5-time point oral glucose tolerance test as a predictor of new-onset diabetes after kidney transplantation.

AIMS: To evaluate the predictive power of the 5-time point oral glucose tolerance test (OGTT) for new-onset diabetes after kidney transplantation (NODAT). METHODS: We performed a retrospective study of 145 patients without diabetes who received kidney transplantations at our hospital. The 5-time point OGTT was performed before transplantation. The area under a receiver-operating characteristic curve (aROC) was used for evaluating the predictive power of 5-time point OGTT values. RESULTS: Seventeen patients developed NODAT within 1 year after transplantation. All postload plasma glucose (PPG) levels were higher in patients who developed NODAT than in those who did not; fasting plasma glucose levels were not different. The aROC for the area under the glucose concentration-time curve was significantly greater than that for fasting plasma glucose. Univariate and multivariate analyses showed that each PPG level was an independent risk factor for NODAT. Furthermore, patients with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) could be stratified with a 1-h plasma glucose (1h-PG) cut-off point of 8.4 mmol/L. The incidences of NODAT were 23.5%, 16.7%, 9.1%, and 0% for patients with IGT+1h-PG ≥8.4 mmol/L,IGT+1h-PG <8.4 mmol/L, NGT+1h-PG ≥ 8.4 mmol/L, and NGT+1h-PG<8.4 mmol/L, respectively. CONCLUSIONS: The area under the glucose concentration-time curve and each PPG concentration during the 5-time point OGTT are strong predictors of NODAT. A 1h-PG cut-off point of 8.4 mmol/L plus NGT/IGT can be used to identify patients at intermediate and high risk of developing NODAT.

Retroperitoneoscopic living donor nephrectomy: short learning curve and our original hybrid technique.

OBJECTIVE: To evaluate the effect of the learning curve for the hybrid technique of retroperitoneoscopic living donor nephrectomy (RDN) on donor and recipient outcomes. METHODS: We retrospectively reviewed 120 consecutive patients who underwent RDN, performed by a laparoscopic surgeon, at Sendai Shakaihoken Hospital between May 2005 and September 2011. A new hybrid technique, in which 2 laparoscopic ports were inserted through a hand-port device and all the procedures except mobilization and taping of ureter and extracting kidney were performed with nonhand-assisted technique, was used. These 120 patients were classified into 4 groups (groups 1-4) of 30 patients each on the basis of the order in which they were operated on by the surgeon. RESULTS: Baseline data including donors' age, gender, and body mass index did not differ among the groups. The time required for graft extraction and overall operative time were significantly longer in group 1 than in the other 3 groups. However, warm ischemia time, blood loss, length of postoperative hospital stay, and graft function did not differ among the groups. CONCLUSION: These results indicate that the hybrid technique of RDN could be performed by surgeons with acceptable outcomes, in donors and recipients, even during the early stages of practicing RDN. Although the time required for graft extraction and overall operative time were much longer during the learning phase, the learning curve was short and improved rapidly after performing only 30 procedures.

Posttransplant increase of body mass index is associated with new-onset diabetes mellitus after kidney transplantation.

New-onset diabetes after transplantation (NODAT) is a serious complication after kidney transplantation. Obesity was widely identified as a modifiable risk factor for NODAT. Body mass index (BMI) is the most frequently used diagnostic indication of obesity, and higher pretransplant BMI has been reported to be an independent risk factor of NODAT. However, the influence of posttransplant increase in BMI on the development of NODAT during outpatient follow-up has not been established. This is a single-centered retrospective study in Japan. We identified 158 consecutive patients who received living donor kidney transplantation in Sendai Shakaihoken Hospital from September 2000 to December 2009. Of these, 101 patients were included in this study. NODAT was defined based on the American Diabetes Association definitions. Fifteen patients developed NODAT with a median follow-up period of 27 (3-109) months. Of these 15 patients with NODAT, 13 patients were diagnosed after the first year of transplantation, with a median follow-up of 29 months, and 2 patients were diagnosed at 3 months after transplantation. Recipient age (HR: 1.06 [1.01-1.13]) and increase in BMI (HR: 1.12 [1.01-1.26]) proved to be independent risk factors of NODAT in multivariate logistic analysis after adjustments for pretransplant 2-hour OGTT level, pretransplant BMI, and use of tacrolimus. This is the first study showing the association between an increase in BMI and the development of NODAT. The increase in BMI might be a risk factor for NODAT. These findings underline the importance of routine BMI measurements in medical practice.

Long-term prognosis of patients with ulcerative colitis treated with cytapheresis therapy.

BACKGROUND: Although accumulating studies in Japan show that cytapheresis (CAP) therapy is safe and effective for the induction of remission of moderate or severe ulcerative colitis (UC), the long-term prognosis of UC patients treated with CAP is unknown. The aim of this study was to determine the long-term prognosis of UC patients treated with CAP. METHODS: Ninety patients treated previously with CAP and followed for more than 3 years were evaluated. The rates of operation, readmission, and use or dose-up of corticosteroid were analyzed as long-term prognosis. RESULTS: Following the first course of CAP treatment, 64% of patients showed clinical improvement (> 4-point decrease in the clinical activity index (CAI)), and 49% of patients achieved clinical remission (CAI ≤ 4). Longer disease duration and lower age at the first CAP treatment correlated significantly with the therapeutic effects of CAP (p = 0.003 and 0.035, respectively). The rates of operation and readmission were significantly lower in patients who showed previous clinical effects of CAP than in those who did not respond to CAP. The rates of operation and readmission were also significantly lower in patients whose treatment was combined with immunomodulators after the initiation of CAP than in patients who did not use immunomodulators. Importantly, the second course of CAP was also effective in most of the patients who showed a clinical response to the first CAP. CONCLUSIONS: Patients who achieve remission after the first CAP therapy may have a good long-term prognosis and a good response to a second CAP therapy even after relapse.

Bile acids induce monocyte differentiation toward interleukin-12 hypo-producing dendritic cells via a TGR5-dependent pathway.

Dendritic cells (DCs) are known as antigen-presenting cells and play a central role in both innate and acquired immunity. Peripheral blood monocytes give rise to resident and recruited DCs in lymph nodes and non-lymphoid tissues. The ligands of nuclear hormone receptors can modulate DC differentiation and so influence various biological functions of DCs. The role of bile acids (BAs) as signalling molecules has recently become apparent, but the functional role of BAs in DC differentiation has not yet been elucidated. We show that DCs derived from human peripheral blood monocytes cultured with a BA produce lower levels of interleukin-12 (IL-12) and tumour necrosis factor-α in response to stimulation with commensal bacterial antigens. Stimulation through the nuclear receptor farnesoid X (FXR) did not affect the differentiation of DCs. However, DCs differentiated with the specific agonist for TGR5, a transmembrane BA receptor, showed an IL-12 hypo-producing phenotype. Expression of TGR5 could only be identified in monocytes and was rapidly down-regulated during monocyte differentiation to DCs. Stimulation with 8-bromoadenosine-cyclic AMP (8-Br-cAMP), which acts downstream of TGR5 signalling, also promoted differentiation into IL-12 hypo-producing DCs. These results indicate that BAs induce the differentiation of IL-12 hypo-producing DCs from monocytes via the TGR5-cAMP pathway.

Prediction of effect of pegylated interferon alpha-2b plus ribavirin combination therapy in patients with chronic hepatitis C infection.

Treatment with pegylated interferon alpha-2b (PEGIFN) plus ribavirin (RBV) is standard therapy for patients with chronic hepatitis C. Although the effectiveness, patients with high titres of group Ib hepatitis C virus (HCV) respond poorly compared to other genotypes. At present, we cannot predict the effect in an individual. Previous studies have used traditional statistical analysis by assuming a linear relationship between clinical features, but most phenomena in the clinical situation are not linearly related. The aim of this study is to predict the effect of PEG IFN plus RBV therapy on an individual patient level using an artificial neural network system (ANN). 156 patients with HCV group 1b from multiple centres were treated with PEGIFN (1.5 µg/kg) plus RBV (400-1000 mg) for 48 weeks. Data on the patients' demographics, laboratory tests, PEGIFN, and RBV doses, early viral responses (EVR), and sustained viral responses were collected. Clinical data were randomly divided into training data set and validation data set and analyzed using multiple logistic regression analysis (MLRs) and ANN to predict individual outcomes. The sensitivities of predictive expression were 0.45 for the MLRs models and 0.82 for the ANNs and specificities were 0.55 for the MLR and 0.88 for the ANN. Non-linear relation analysis showed that EVR, serum creatinine, initial dose of Ribavirin, gender and age were important predictive factors, suggesting non-linearly related to outcome. In conclusion, ANN was more accurate than MLRs in predicting the outcome of PEGIFN plus RBV therapy in patients with group 1b HCV.

Prediction of metabolic syndrome using artificial neural network system based on clinical data including insulin resistance index and serum adiponectin.

OBJECTIVE: This study aimed to predict the 6-year incidence of metabolic syndrome (MetS) using an artificial neural network (ANN) system and multiple logistic regression (MLR) analysis based on clinical factors, including the insulin resistance index calculated by homeostasis model assessment (HOMA-IR). DESIGN: Subjects were recruited from participants in annual health check-ups in both 2000 and 2006. A total of 410 Japanese male teachers and other workers at Keio University, 30-59 years of age at baseline, participated in this retrospective cohort study. MEASUREMENTS: Clinical parameters were randomly divided into a training dataset and a validation dataset, and the ANN system and MLR analysis were applied to predict individual incidences. The leave some out cross validation method was used for validation. RESULTS: The sensitivity of the prediction was 0.27 for the MLR model and 0.93 for the ANN system, while specificities were 0.95 and 0.91, respectively. Sensitivity analysis employing the ANN system identified BMI, age, diastolic blood pressure, HDL-cholesterol, LDL-cholesterol and HOMA-IR as important predictors, suggesting these factors to be non-linearly related to the outcome. CONCLUSION: We successfully predicted the 6-year incidence of MetS using an ANN system based on clinical data, including HOMA-IR and serum adiponectin, in Japanese male subjects.

Correlation between endocytoscopy and conventional histopathology in microstructural features of ulcerative colitis.

BACKGROUND: Routine diagnosis of the histopathological activity of ulcerative colitis (UC) requires multiple biopsy samples, and an endocytoscopy system (ECS) provides real-time ultra-magnifying microscopic imaging in vivo. METHODS: We have established an ECS score (ECSS) to determine a histopathological activity index of UC. Fifty-five UC patients (mean age 40.7 years; 67% men) were enrolled. A super-magnifying ECS with magnification 450× was used, and sample biopsies were obtained. Matts' histopathological grade was determined, to evaluate disease severity, by two pathologists, with consensus. The ECSS of UC was independently determined by at least two investigators, with consensus. In total, 76 pairs of ECSS and Matts' histopathological grades were independently acquired. To validate the ECSS, inter-observer agreement between three endoscopists, with consensus, and another endoscopist, was calculated as the kappa value. We also evaluated the correlation between the ECSS and Matts' histopathological grade, and between the conventional Matts' endoscopic grade and Matts' histopathological grade. RESULTS: The ECSS of UC intestinal mucosa, i.e., the sum of the indices for shape (0-3) and distance between crypts (0-2), and the visibility of superficial microvessels (0-1), showed a strong correlation with Matts' histopathological grades (ρ = 0.713, P < 0.001); as well, there was a strong correlation between the conventional Matts' endoscopic grade and Matts' histopathological grade (ρ = 0.694, P < 0.001). Furthermore, the ECSS showed high reproducibility (κ = 0.79, 95% confidence interval [CI] 0.71-0.87). CONCLUSIONS: Our novel ECSS has good predictive value for the histopathological activity of UC.

Imbalance of NKp44(+)NKp46(-) and NKp44(-)NKp46(+) natural killer cells in the intestinal mucosa of patients with Crohn's disease.

BACKGROUND & AIMS: Mucosal natural killer (NK) cells that produce interleukin (IL)-22 mediate intestinal homeostasis and inflammation in mice. However, their role in the pathogenesis of human inflammatory bowel diseases (IBDs) is not known. We investigated intestinal NK cells in intestinal mucosa samples of patients with Crohn's disease (CD). METHODS: We isolated lamina propria NK cells from intestinal mucosal samples of patients with IBD and subjects without IBD (controls) and analyzed expression patterns of cell surface molecules and cytokine production. Interactions between lamina propria NK cells and intestinal macrophages were examined. RESULTS: In intestinal mucosa samples from controls, NKp44 and NKp46 were expressed differentially on CD3(-)CD56(+) NK cells, NKp44(+)NKp46(-) (NKp44(+)) NK cells expressed CD127 and the transcription factor retinoic acid-related orphan receptor C (RORC) and produced IL-22 whereas NKp44(-)NKp46(+) (NKp46(+)) NK cells did not express CD127 or RORC and produced interferon (IFN)-gamma. NKp46(+) NK cells were predominant in intestinal mucosa of patients with CD compared with controls or patients with ulcerative colitis. Upon interaction with intestinal inflammatory macrophages NKp46(+), NK cells from patients with CD were activated via IL-23 and produced IFN-gamma; this activation required cell-to-cell contact. CONCLUSIONS: The balance of NKp44(+)/NKp46(+) NK cells is disrupted in intestinal mucosa of patients with CD. NKp46(+) NK cells might mediate the pathogenesis of CD by producing IFN-gamma.

Rapid endoscopic improvement is important for 1-year avoidance of colectomy but not for the long-term prognosis in cyclosporine A treatment for ulcerative colitis.

BACKGROUND: Intravenous (IV) cyclosporine A (CSA) is one of the treatments of choice for patients with steroid-refractory severe ulcerative colitis (UC). In this study, we evaluated the overall experience with CSA treatment in UC patients, from their initial response to long-term prognosis. METHODS: The medical records of 72 patients admitted to our hospital with a severe UC flare-up and treated with IV CSA between November 1996 and October 2008 were reviewed retrospectively. The initial response to CSA was assessed using a clinical activity index, and colectomy was assigned as the endpoint for the long-term prognosis. RESULTS: Overall, 53 of 72 (73.6%) patients responded initially to CSA. We could not determine any specific parameters that predicted an initial response. A life-table analysis for all patients revealed that 54.4% of patients required a colectomy within 11 years. The long-term risk of surgery was associated with a shorter disease duration, history of adverse reactions against medications and lack of immunomodulator use. In addition, endoscopic improvement at day 14 was associated with colectomy at 1 year, but not with the long-term prognosis. CONCLUSIONS: Although CSA can exert high initial efficacy for severe attacks of UC, >50% of patients who relapse require a colectomy. Specifically, mucosal healing evaluated by endoscopy was associated with the 1-year colectomy rate. In contrast, a history of adverse drug reactions was correlated with the long-term colectomy rate. Therefore, we propose that treatment of severe UC with CSA requires consideration of both initial remission and long-term maintenance as management goals.

In vivo visualization of trophozoites in patients with amoebic colitis by using a newly developed endocytoscope.

BACKGROUND: The endocytoscopy system (ECS) is a new method to provide real-time super-magnifying microscopic imaging in vivo. Routine diagnosis of amebic colitis requires multiple tests that are both time consuming and costly. OBJECTIVE: To determine the feasibility of ECS to directly detect the amebic parasites in vivo. DESIGN: Prospective, single-center, pilot study. SETTING: Tertiary-care university hospital. PATIENTS: This study involved 5 patients who were suspected to have amebic colitis by conventional colonoscopy in our institute. INTERVENTIONS: A super-magnifying ECS with 450 x magnification. MAIN OUTCOME MEASUREMENTS: We compared ECS findings with those of conventional methods-serum antibody tests and histology of colon biopsy specimens. RESULTS: We successfully visualized the amebic trophozoites in all 5 cases. In contrast, 3 specimens had positive results on serology, and 3 had positive histology results on hematoxylin and eosin staining. LIMITATIONS: Pilot study with a limited number of patients. Findings were compared only with serology and histology findings. CONCLUSIONS: ECS would be a useful tool for the prompt diagnosis of amebic colitis via the real-time in vivo visualization of amebic trophozoites.

Monocyte chemoattractant protein-1 contributes to gut homeostasis and intestinal inflammation by composition of IL-10-producing regulatory macrophage subset.

Lamina propria macrophages (LPMs) spontaneously produce large amounts of anti-inflammatory IL-10 and play a central role in regulation of immune responses against commensal bacteria. MCP-1 is a chemokine that plays an important role in recruitment of monocytes and macrophages to inflamed tissues. We demonstrated that, in addition to IL-10, LPMs produced large amounts of MCP-1, even in a steady state. MCP-1 deficiency caused impaired IL-10 production by LPMs and led to exacerbation of dextran sulfate sodium-induced acute colitis. As an explanation of this impaired IL-10 production by LPMs, we found that LPMs could be separated into two subsets with distinct side-scattered properties, namely LPM1 (CD11b(+)F4/80(+)CD11c(-)SSC(hi)) and LPM2 (CD11b(+)F4/80(+)CD11c(-)SSC(lo)). Unlike LPM1, the LPM2 subset migrated in response to MCP-1 and produced a larger amount of IL-10 in response to commensal bacteria. LPMs isolated from MCP-1-deficient mice produced less IL-10 as a consequence of the lack of the MCP-1-dependent LPM2 population. This imbalanced composition in LPM population may be involved in the susceptibility to DSS-induced colitis in MCP-1-deficient mice. Our results suggest that endogenous MCP-1 contributes to the composition of resident LPM subsets in the intestine. Moreover, MCP-1-dependent LPM2 subset may play an important role in maintenance of gut homeostasis in the steady state, and in the termination of excess inflammatory responses in the intestine, by producing IL-10.