A novel method to localize patency capsule by ileo-colonoscopy facilitates endoscopic assessment of the small and large intestine in patients with Crohn's disease.

INTRODUCTION: Patients with Crohn's disease (CD) require an assessment of small bowel lesions, while difficulties exist in performing small intestinal examinations especially in small-sized medical offices. Small bowel capsule endoscopy (SBCE) is handy and can be performed in most clinical settings. The only drawback of SBCE is a requirement of patency testing prior to the exam because it sometimes requires CT scanning to localize the ingested patency capsule (PC), which may be a substantial burden for the patient. We have developed a novel PC detection system named PICS (Patency capsule, Ileo-Colonoscopy and Small bowel capsule endoscopy) method by which we can avoid CT scanning. In the PICS method, Ileo-Colonoscopy (ICS) is performed after 30 to 33 hours of PC ingestion and the PC can be localized by ICS in patients who have not excreted the PC, and the entire intestine can be examined in combination with subsequent SBCE without additional bowel preparation. The aim of this study was to assess the usefulness and safety of the PICS method for CD patients. METHODS: CD patients who underwent PICS method from April 2021 to March 2023 were reviewed for clinical data, outcome of PICS method including the rates of PC detection by ICS, the number of patients underwent SBCE, and adverse events. Lewis score was used to assess SBCE results. RESULTS: The PICS method was performed in 54 patients. The median age of patients was 28.5 years old and 64.8% of them were ileo-colic type. The median disease duration was 10.5 months and 24.1% had history of small bowel resection. Five cases (9.3%) confirmed gastrointestinal patency by ICS and none of the cases required CT scanning. One patient who could not be confirmed patency by ICS, and the other patient who excreted PC but was found ileal stenosis by ICS did not undergo SBCE. Remaining 52 patients received SBCE and the median Lewis score of them was 0 (IQR 0, 450). There were no adverse events including small bowel obstruction by PC and SBCE retention in this series. CONCLUSION: The PICS method is not only feasible and safe but also convenient to assess disease extent in patients with CD. By localizing PC with ICS, additional CT scanning could be unnecessary for SBCE, which benefits both physicians and CD patients.

Efficacy and safety of filgotinib for ulcerative colitis: A real-world multicenter retrospective study in Japan.

BACKGROUND AND AIMS: While filgotinib, an oral Janus kinase (JAK) 1 preferential inhibitor, is approved for moderately to severely active ulcerative colitis (UC), real-world studies assessing its short- and long-term efficacy and safety are limited. METHODS: This is a multicenter, retrospective study of UC patients who started filgotinib between March 2022 and September 2023. The primary outcome was clinical remission, defined as a partial Mayo score ≤1 with a rectal bleeding score of 0, or Simple Clinical Colitis Activity Index (SCCAI) ≤2 with a blood-in-stool score of 0. Secondary outcomes included clinical response, corticosteroid-free remission, and endoscopic improvement. Outcomes were assessed at 10, 26, and 58 weeks based on patients with available follow-up. Adverse events were evaluated. RESULTS: We identified 238 UC patients and 54% had prior exposure to biologics/JAK inhibitors. The median baseline partial Mayo score and SCCAI were 5 (IQR 3-6) and 4 (IQR 2-7). Clinical remission rates based on per-protocol analysis at 10, 26, and 58 weeks were 47% (70/149), 55.8% (48/86), and 64.6% (31/48), respectively. At a median follow-up of 28 weeks (IQR 10-54) with a discontinuation rate of 39%, the rates of clinical remission, clinical response, corticosteroid-free remission, and endoscopic improvement were 39.9% (81/203), 54.7% (111/203), and 36.5% (74/203), and 43.5% (10/23), respectively. These rates were comparable between biologic/JAK inhibitor-naïve and -experienced patients. While three patients (1.3%) developed herpes zoster infection, no cases of thrombosis or death were reported. CONCLUSIONS: Real-world data demonstrate favourable clinical and safety outcomes of filgotinib for UC.

Severe Disease Activity May Predispose Patients to Post-colectomy Duodenitis Associated with Ulcerative Colitis.

Objective Diffuse mucosal inflammation in the duodenum, distinct from peptic ulcer disease, has been repeatedly reported in patients with ulcerative colitis (UC). The pathogenesis of this complication remains uncertain; however, colectomy for medically refractory UC appears to trigger duodenitis. Cases in which colectomy was performed for UC were analyzed to characterize UC-related duodenitis after colectomy. Methods A retrospective case-control study of UC-related duodenitis that developed after colectomy in medically refractory UC between January 2011 and June 2020 was conducted. UC-related duodenitis was diagnosed based on typical clinical, endoscopic, and histological findings, and no duodenitis was endoscopically defined by the normal duodenal mucosa. Clinical and laboratory data, disease severity, and medications used were collected and compared between the UC-related and non-duodenitis cases. Results Ten UC-related duodenitis and 35 non-duodenitis cases were identified among 45 patients with UC who underwent esophagogastroduodenoscopy after colectomy. Disease severity, defined by the C-reactive protein level and partial Mayo score prior to colectomy, was significantly higher in duodenitis patients than in non-duodenitis patients. In comparison to non-duodenitis patients, duodenitis patients more frequently received rescue therapies with calcineurin inhibitors or anti-TNF-α agents at the time of colectomy (100% vs. 65.7%). Conclusion Patients with UC with higher disease activity, especially those who require rescue therapies with calcineurin inhibitors and anti-TNF-α agents, may be prone to developing UC-related duodenitis after colectomy.

Crohn's disease may promote inflammation in IgA nephropathy: a case-control study of patients undergoing kidney biopsy.

Intestinal immunity has been closely associated with the pathogenesis and progression of renal diseases, a relationship known as the "gut-kidney axis." To determine the association between immunoglobulin A nephropathy (IgAN) and Crohn's disease (CD), a clinico-pathological study was performed on patients who had IgAN with CD (CD-IgAN) and without CD (NOS-IgAN). We enrolled 29 patients diagnosed with IgAN via renal biopsy at the Tokyo Yamate Medical Center from 2009 to 2017. The patients were divided into CD-IgAN (n = 18) and NOS-IgAN (n = 11) and evaluated for clinical and pathological findings. IgA subclasses and galactose-deficient IgA1 (Gd-IgA1) were examined via immunohistochemistry using formalin-fixed paraffin-embedded sections from renal biopsy. Our results showed no significant difference in the extent of mesangial IgA subclasses or Gd-IgA1 deposition according to the presence or absence of CD. Pathologically, however, those with CD-IgAN had remarkably higher percentage of global glomerulosclerosis and extent of interstitial fibrosis and tubular atrophy (IF/TA) compared to those with NOS-IgAN. Moreover, the extent of macrophage infiltration in the glomerulus and interstitium was significantly higher in CD-IgAN than in NOS-IgAN. Clinically, the CD-IgAN group had significantly worse responsiveness to steroid treatment compared to the NOS-IgAN group. In conclusion, the similar immunological characteristics of deposited IgA molecules in the glomeruli between the CD-IgAN and NOS-IgAN groups might suggest their etiological similarity. However, a renal pathology showing advanced glomerular and tubulointerstitial sclerosis accompanying increased macrophage infiltration and highly resistant clinical features in patients with CD-IgAN suggests that some pathophysiological factors in CD, including abnormal intestinal immunity, may promote and activate the inflammatory process in IgAN via undetermined mechanisms.

Safety Prediction of Infants Born to Mothers with Crohn's Disease Treated with Biological Agents in the Late Gestation Period.

OBJECTIVES: Knowledge gaps exist in the use of biologics for pregnant patients with Crohn's disease (CD), especially the usage of ustekinumab (UST) and infliximab (IFX) infusion during the late gestation period. In this case series, we investigated perinatal and neonatal outcomes and pharmacokinetics of these biologics in pregnant CD patients. METHODS: Pregnant CD patients under treatment with IFX or UST during January 2017 to December 2019 were monitored. Growth and development of their babies were followed up to six months. Drug concentrations were measured in maternal peripheral and cord blood at delivery and infants' blood at six months of age. RESULTS: Four cases were kept IFX treatment until late gestation (median last dose: 31.2 weeks). One case received UST until 23 weeks of gestation. All cases were in clinical remission but moderately undernourished. Babies were delivered by cesarean section at full term without any complications or congenital abnormalities. No growth or developmental defects and no susceptibility to infections were observed by six months. However, two babies whose mothers received IFX after 30 weeks of gestation were detected IFX in their blood at six months of age (0.94 and 0.24 pg/ml). Concentrations of UST in maternal and cord blood were 267.7 and 756.5 ng/ml, respectively. UST was not detected in the infant at six months of age. CONCLUSIONS: Administration of UST or IFX to pregnant patients with CD is safe, particularly IFX to be given in the late gestation period. Understanding of the pharmacokinetics of biologics in maternal-infant interactions may improve the management of pregnant CD patients.

Polymorphism at rs9264942 is associated with HLA-C expression and inflammatory bowel disease in the Japanese.

An expression quantitative trait locus (eQTL) single-nucleotide polymorphism (SNP) at rs9264942 was earlier associated with human leukocyte antigen (HLA)-C expression in Europeans. HLA-C has also been related to inflammatory bowel disease (IBD) risk in the Japanese. This study examined whether an eQTL SNP at rs9264942 could regulate HLA-C expression and whether four SNP haplotypes, including the eQTL SNP at rs9264942 and three SNPs at rs2270191, rs3132550, and rs6915986 of IBD risk carried in the HLA-C*12:02~B*52:01~DRB1*15:02 allele, were associated with IBD in the Japanese. HLA-C expression on CD3e+CD8a+ lymphocytes was significantly higher for the CC or CT genotype than for the TT genotype of rs9264942. The TACC haplotype of the four SNPs was associated with a strong susceptibility to ulcerative colitis (UC) but protection against Crohn's disease (CD) as well as with disease clinical outcome. While UC protectivity was significant but CD susceptibility was not for the CGTT haplotype, the significance of UC protectivity disappeared but CD susceptibility reached significance for the CGCT haplotype. In conclusion, our findings support that the eQTL SNP at rs9264942 regulates HLA-C expression in the Japanese and suggest that the four SNPs, which are in strong linkage disequilibrium, may be surrogate marker candidates of a particular HLA haplotype, HLA-C*12:02~B*52:01~DRB1*15:02, related to IBD susceptibility and disease outcome.

A case of refractory chronic pouchitis successfully treated with tofacitinib.

We describe a case of refractory pouchitis successfully treated with tofacitinib. The patient was a 20-year-old woman diagnosed with ulcerative colitis at the age of 14 years. She underwent surgery at the age of 18 years for chronic active inflammation, despite an optimal medication regimen. Ten months after surgery, she was diagnosed with pouchitis. She did not respond to conventional conservative treatment; thus, the case was considered as that of refractory chronic pouchitis. Anti-tumor necrosis factor-α (TNF-α) therapy was administered, which led to some improvement; however, pouchitis recurred. Systemic steroid and vedolizumab were also administered, but the response was unsatisfactory. Therefore, surgery was considered; however, the patient refused to undergo surgery. As identical therapies are recommended for ulcerative colitis and pouchitis, they are considered to have a common etiology. Therefore, we considered tofacitinib therapy in this case. After obtaining the patient's informed consent, tofacitinib treatment was initiated. The therapy led to improvement in her symptoms as well as in the appearance of the pouch when observed on endoscopy, and surgery was avoided. Thus, tofacitinib may be considered a therapy option for refractory chronic pouchitis.

Efficacy of Granulocyte and Monocyte Adsorptive Apheresis in Patients With Inflammatory Bowel Disease Showing Lost Response to Infliximab.

BACKGROUND AND AIMS: In inflammatory bowel disease [IBD] patients, antibody-to-infliximab [ATI] generation is responsible for loss of response [LOR] and infusion reaction [IR] to infliximab. An immuno-therapeutic approach is considered an option to overcome LOR. Granulocyte/monocyte adsorptive apheresis [GMA] using an Adacolumn has been shown to have clinical efficacy together with immunomodulatory effects in IBD patients. METHODS: We developed an ATI-CAI assay utilizing a C1q immobilized plate and applied it to measure ATI in patients who were receiving infliximab, including 56 with sustained response, 76 with LOR and six with IR. Furthermore, 14 patients with LOR and two with paradoxical skin reactions who received infliximab + GMA combination therapy were analysed. RESULTS: Fourteen patients with LOR, seven with Crohn's disease and seven with ulcerative colitis, showed significantly improved clinical indices [p = 0.0009], and decreased ATI [p = 0.0171] and interleukin-6 [p = 0.0537] levels at week 8 following initiation of infliximab + GMA therapy. Nine patients who received combination therapy achieved remission, which was maintained to week 24 with infliximab alone. Additionally, cutaneous lesions in two patients with IR were improved. ATI-CAI assay efficiency was not influenced by infliximab concentration during the test. Pre- and post-infliximab infusion ATI levels were not different. Patients with ATI greater than the 0.153 µg/mL cut-off value were likely to experience LOR [odds ratio 3.0]. CONCLUSIONS: Patients who received infliximab + GMA therapy appeared to regain clinical response to infliximab by a decrease in ATI level. Furthermore, the concentration of infliximab in the test did not influence ATI measurement, but was associated with clinical response.

[Three cases of severe and fulminating ulcerative colitis with megacolon treated with continuous intravenous infusion of cyclosporine].

Dilatation of the colon in severe and fulminating ulcerative colitis is a sign of toxic megacolon and emergency surgery is usually the favored treatment option. Here we describe our experience with three cases of ulcerative colitis with megacolon in which surgery was avoided by treating the patients with a continuous intravenous infusion of cyclosporine, with full cooperation of the surgeons. We recommend that continuous intravenous infusion of cyclosporine be considered as an effective option for the conservative management of severe, fulminating ulcerative colitis with megacolon.

Significance of Conducting 2 Types of Fecal Tests in Patients With Ulcerative Colitis.

BACKGROUND & AIMS: We compared the diagnostic accuracy of the fecal calprotectin (FCP) test vs the fecal immunochemical blood test (FIT) in determining the endoscopic severity and predicting outcomes of patients with ulcerative colitis (UC). METHODS: We performed a nationwide study of 879 patients with UC, enrolled at medical centers across Japan, from March 2015 to March 2017. We collected data on fecal biomarkers, endoscopic severities, and other clinical indices from Cohort 1 (n = 427) and assessed the diagnostic accuracy of FCP measurement and FIT results in determining clinical severity, based on Mayo score, and endoscopic remission, based on Mayo endoscopic sub-score (MES) or UC endoscopic index of severity. We also followed 452 patients in clinical remission from UC (Cohort 2) for 12 months and evaluated the associations of FCP levels and FIT results with clinical recurrence. RESULTS: The levels of FCP and FIT each correlated with the MES and UC endoscopic index of severity. There were no significant differences in the areas under the curve of FCP vs FIT in distinguishing patients with MES≤1 from those with MES≥2 (P = .394) or in distinguishing patients with MES=0 from those with MES≥1 (P = .178). Among 405 patients in clinical remission at baseline, 38 (9.4%) had UC recurrences within 3 months and 90 (22.2%) had recurrences within 12 months. FCP≥146 mg/kg (hazard ratio [HR], 4.83; 95% confidence interval [CI], 2.80-8.33) and FIT≥77 ng/mL (HR, 2.92; 95% CI, 1.76-4.83) were independently associated with clinical recurrence within 12 months. UC recurred within 12 months in 69% of patients with levels of FCP≥146 mg/kg and FIT ≥77 ng/mL; this value was significantly higher than the rate of recurrence in patients with levels of FCP≥146 mg/kg and FIT <77 ng/mL (31.5%, P < .001) or patients with levels of FCP<146 mg/kg and FIT ≥77 ng/mL (30.0%, P < .001). CONCLUSION: In a nationwide study of patients with UC in Japan, we found that the level of FCP and FIT could each identify patients with endoscopic markers of disease severity (MES≥2). The combination of FCP and FIT results can identify patients in remission who are at risk for disease recurrence. Clinical Trials Registry no: UMIN000017650 (http://www.umin.ac.jp/ctr/).

Development of a C1q-immobilized (Cim) assay to measure total antibodies to infliximab and its clinical relevance in patients with inflammatory bowel disease.

OBJECTIVE: Determination of antibodies to infliximab (ATI) is desirable for the management of patients with inflammatory bowel disease (IBD) who receive infliximab. Conventional ligand-binding ATI-assays detect only free-form of ATI, potentially increasing the proportion of patients with undetectable ATI, but with adequate trough infliximab (TRI) level who experience loss of response (LOR) to infliximab. We investigated this assertion using a novel ATI-Cim assay. METHODS: An ATI-Cim assay was developed by utilizing a C1q-immobilized plate, detecting free-form and ATI-infliximab complexes. Plasma ATI in 137 consecutive IBD patients, 56 with sustained clinical response (SCR), 76 with LOR and 5 with infusion reactions was measured. RESULTS: ATI levels reached a plateau following addition of up to 25 µg/mL infliximab to different concentrations of free-form ATI. ATI concentration did not significantly change during infliximab infusion (P = 0.4316). ATI concentration > 0.153 µg/mL was associated with LOR (odds ratio 3.0: 95%, confidence interval 1.5 to 6.1, P = 0.0029). The number of patients with undetectable ATI was higher in SCR than in LOR, 53.6% vs 22.4% (P = 0.0004). Patients with SCR and LOR were divided into 4 subgroups by combined cut-off ATI and TRI values. (A) ATI > 0.153 µg/mL and TRI ≤ 2 µg/mL; (B) ATI > 0.153 µg/mL and TRI > 2 µg/mL; (C) ATI ≤ 0.153 µg/mL and TRI ≤ 2 µg/mL; (D) ATI ≤ 0.153 µg/mL and TRI > 2 µg/mL. The frequency of LOR showed a decreasing trend from subgroup A to D, 80.8%, 64.1%, 55.2% and 36.8%, respectively (P = 0.0003). CONCLUSIONS: The measured ATI level appeared to define the patients' response to infliximab. Combining ATI and trough infliximab levels should help to understand the mechanism of LOR and make therapeutic algorithms.

Rat Bite Fever Caused by Streptobacillus moniliformis in a Cirrhotic Patient Initially Presenting with Various Systemic Features Resembling Henoch-Schönlein Purpura.

We herein report the case of a 61-year-old Japanese cirrhotic patient who developed rat bite fever (RBF) and whose first presentation was serious clinical features mimicking those of Henoch-Schönlein purpura (HSP). In addition to the critical clinical conditions, since the histopathology from purpuric skin eruptions was not inconsistent with that of HSP, therapy with prednisolone was promptly started in order to prevent his death. However, initial blood culture on admission yielded a small and slow-growing bacterial growth, which was gradually revealed by further subculture to be a peculiar bacterium, Streptobacillus moniliformis, leading to a definitive diagnosis of RBF. After the immediate cessation of prednisolone, the patient was treated with a more appropriate antibiotic and consequently made a full recovery. An immunocompromised condition with seriously decompensated liver cirrhosis together with moderately severe chronic kidney disease (CKD) in this patient probably exacerbated the severity of the disease.

Food antigen-induced immune responses in Crohn's disease patients and experimental colitis mice.

BACKGROUND: In Crohn's disease (CD), the involvement of food antigens in immune responses remains unclear. The objective of this study was to detect immune responses against food antigens in CD patients and examine the mechanism in a mouse model of colitis. METHODS: We enrolled 98 CD patients, 50 ulcerative colitis patients, and 52 healthy controls (HCs) to compare the levels of serum immunoglobulin (Ig)Gs against 88 foods. The presence of serum IgGs against foods was also examined in interleukin (IL)-10 knockout (KO) mice in which CD4(+) T cell activation by antigenic food protein was assessed. Mice transferred with IL-10 KO cells received diets with or without food antigens, and the development of colitis was evaluated. RESULTS: The prevalence of IgGs against various foods, especially vegetables, grains, and nuts, was significantly higher in CD patients than in HCs. Similarly, the prevalence of IgGs against food proteins was higher in IL-10 KO mice than in BALB/c mice. Beta-conglycinin, identified as an antigenic food proteins in IL-10 KO mice, induced CD4(+) T cell production of interferon-γ and IL-17 through dendritic cell antigen presentation. Elimination of the food antigens ameliorated the development of colitis in mice without altering the composition of their intestinal microbiota. CONCLUSIONS: In CD colitis mice, intestinal inflammation via CD4(+) T cell hyperactivation was induced by food antigens associated with high serum IgG levels and was ameliorated by the elimination of food antigens. This disrupted immunological tolerance to food antigen, which might act as an exacerbating factor, remains to be elucidated in CD patients.

Daikenchuto, a traditional Japanese herbal medicine, for the maintenance of surgically induced remission in patients with Crohn's disease: a retrospective analysis of 258 patients.

PURPOSE: Despite numerous studies, the best postoperative therapy for Crohn's disease is still undefined. We retrospectively evaluated the effects of postoperative maintenance therapy with daikenchuto, a traditional Japanese Kampo medicine, on the reoperation rate at 3 years in patients with Crohn's disease. METHODS: A total of 258 patients who underwent surgery for Crohn's disease were identified for the study. For the prevention of postoperative recurrence, patients were stratified to receive 5-aminosalicylic acid, azathioprine or daikenchuto, and their effects on preventing reoperation at 3 years were evaluated. RESULTS: Of the 258 patients, 44 required reoperation with intestinal resection within 3 years due to disease recurrence. The 3-year reoperation rate was significantly lower in the postoperative daikenchuto group than in the non-daikenchuto group (11.3 vs. 24.5 %, P = 0.01), and was similarly significantly lower in the postoperative 5-aminosalicylic acid group than in the non-5-aminosalicylic acid group (14.8 vs. 29.6 %, P = 0.0049). A multivariate Cox analysis showed that postoperative daikenchuto (P = 0.035) and postoperative 5-aminosalicylic acid (P = 0.022) were significantly and independently associated with the rate of reoperation at 3 years in patients with Crohn's disease. CONCLUSION: We propose that continuous daikenchuto therapy is a clinically useful and feasible maintenance therapy for the prevention of postoperative reoperation in patients with Crohn's disease.

[Long-term outcomes of ileal pouch-anal canal anastomosis in children with ulcerative colitis].

The present study investigated the long-term outcomes of restorative proctocolectomy in pediatric patients with ulcerative colitis (UC). We report a series of 25 patients who underwent total proctocolectomy with ileal pouch-anal canal anastomosis (IACA). Surgery was performed for medically intractable colitis and severe colitis in 14 and 11 patients, respectively. Early and late complications were observed in 6 (24%) and 14 (56%) patients, respectively. The long-term quality of life outcomes were satisfactory, including both bowel function and social function. Growth retardation was observed in 6 patients. Five patients exhibited catch-up growth and 3 patients overcame growth retardation. Patients with growth retardation tended to have a younger onset and longer duration of UC, as well as a longer duration and higher total dose of steroid use. In conclusion, the long-term outcomes of pediatric patients with UC undergoing IACA are satisfactory. Furthermore, to minimize the risk of growth retardation, surgery should be performed without delay.

Processed blood volume impacts clinical efficacy in patients with ulcerative colitis undergoing adsorptive depletion of myeloid lineage leucocytes.

BACKGROUND: Hitherto, therapeutic depletion of granulocytes and monocytes by adsorption (GMA) has been associated with significant and insignificant efficacy in patients with ulcerative colitis (UC). Further, the processed blood volume in one GMA session has been fixed at 30 mL/min × 60 min, regardless of patients' body weight (BW). We were interested to see the efficacy and safety of GMA when administered in relation to patients' BW. METHODS: Sixty patients were randomly assigned to the routine GMA (n = 30) and to GMA adjusted to patients' BW, 60 mL/kg (n = 30). GMA was done with the Adacolumn, up to 10 sessions over 10 weeks. At entry and 1 week post last GMA, patients were clinically and endoscopically evaluated. Remission was defined as clinical activity index (CAI) ≤4, whereas mucosal remission was defined as endoscopic index (EI) ≤3. RESULTS: In the BW group, the processed volume/session was 3,260 ± 581 versus 1,800 mL in the routine group (P < 0.001). In the BW group, 25 of 30 patients (83.3%) achieved remission versus 19 of 30 patients (63.3%) in the routine group. The average CAI in the BW group fell from 9.6 ± 2.6 to 2.3 ± 2.1 versus from 9.1 ± 2.4 to 4.0 ± 2.1 (P < 0.05) in the routine group. Similarly, the EI in the BW group fell from 9.4 ± 1.3 to 2.1 ± 2.1 versus from 9.2 ± 1.8 to 4.5 ± 2.3 (P < 0.01). CONCLUSIONS: GMA adjusted to patients' BW and at a vastly greater processed volume produces significantly higher efficacy as compared with the routine GMA protocol. Further, in this study, up to twofold higher processed volume caused no safety concern.

Conception and pregnancy outcome in women with inflammatory bowel disease: A multicentre study from Japan.

BACKGROUND: Neither conceptions and pregnancy outcomes nor the safety of medications for childbearing inflammatory bowel disease (IBD) patients has been investigated in Asia. The aim of this study is to analyse conception and pregnancy outcomes of Japanese female IBD patients. METHODS: We conducted a retrospective cohort study of pregnant IBD patients at 6 institutions. The incidences of abortion, Caesarean delivery, low birth weight (LBW) (<2500g), and congenital malformation were analysed in these patients. Risk factors associated with adverse outcomes in IBD patients were also assessed. RESULTS: A total of 325 patients experienced 534 conceptions. Among these, 303 conceptions (57%) were observed during/after disease onset. Although conceptions and pregnancy outcomes after disease onset were comparable to the observed levels prior to disease onset in UC patients, the incidences of spontaneous abortion (OR 5.3; 95%CI 1.1-25.0) and Caesarean delivery (OR 4.8; 95%CI 1.5-15.0) were significantly higher in Crohn's disease (CD) patients whose conceptions occurred after disease onset compared to CD patients whose conceptions occurred before disease onset. The incidences of spontaneous abortion, LBW, and Caesarean delivery were higher in CD patients who had a history of surgery for perianal lesions than in those who did not have perianal lesions or who had ulcerative colitis (UC). In the IBD patients studied after disease onset, independent risk factors for spontaneous abortions included a history of previous treatment for sterility (OR 2.9; 95%CI 1.2-7.0). Independent risk factors for Caesarean operation (OR 4.1, 95% CI: 1.7-10.1) and LBW (OR 3.5, 95% CI: 1.3-9.1) included a history of bowel resection for the treatment of IBD. Congenital malformation was not associated with the factors of type of disease, smoking, and previous surgery. CONCLUSION: In Japanese UC patients, conception and pregnancy outcomes after disease onset were comparable to the outcomes observed prior to disease onset, whereas CD appeared to be associated with adverse outcomes. Caesarean operation and LBW were more frequently observed in CD patients who had a history of surgery for perianal lesions and bowel resection.

[A case of HIV infection associated with ulcerative colitis].

We describe a 42-year-old-man with HIV infection who developed ulcerative colitis. Ulcerative colitis was diagnosed on the basis of clinical symptoms, and the findings of colonoscopy, pathology and culture. Although remission of ulcerative colitis was induced by PSL and SASP, HIV infection progressed. Treatment with highly active antiretroviral therapy (HAART) was started. HIV viral load decreased to less than 50copies/ml and CD4 counts increased to over 400/microl. After discontinuance of PSL and SASP, he is still in good condition. This is the first report of HIV infection associated with ulcerative colitis in Japan. A relationship between immune disorder in advanced HIV infection and inflammatory bowel disease was suggested. Ulcerative colitis might be an important complication in HIV infection.

Restorative proctocolectomy for pediatric patients with ulcerative colitis.

PURPOSE: A restorative proctocolectomy has become an elective surgical treatment for patients with ulcerative colitis (UC). In children with UC, however, the role of this procedure has not yet been well evaluated. We investigated the postoperative status of pediatric patients with UC regarding the side effects of steroids, postoperative complications, and growth. METHODS: The medical records of 15 patients with UC who underwent a restorative proctocolectomy between August 1993 and October 2003 were retrospectively reviewed. RESULTS: Their mean age was 12.6 +/- 3.4 years (range 5.7-15.7; boys: 9, girls: 6). All patients had total colitis, except for one who had left-sided colitis. The mean cumulative dose of preoperative prednisolone was 6201 +/- 7980 mg (mean +/- SD). The operative indications were an unsuccessful response to medical treatments in 12 patients (80%) and severe colitis in 3 patients (20%). Surgery was performed in one stage in 6 patients and in two stages in 9 patients. Seven patients (47%) demonstrated growth retardation at the time of operation. Steroid-related complications were seen in 3 cases, i.e., steroid myopathy, glaucoma, and cataracts, respectively. As early postoperative complications, an intestinal obstruction was seen in 2 patients, peritonitis in 1, and pancreatitis in 1. As late complications, anastomotic stenosis was observed in 5 patients, pouchitis in 4, residual proctitis in 3, and anal or proctovaginal fistula in 2. An intestinal obstruction, peristomal pyoderma gangrenosum, and dehydration each was seen in 1 patient. A growth "catch-up" was obtained for all but one patient. All patients became free of corticosteroids. CONCLUSION: A restorative proctocolectomy was found to be an effective treatment alternative even in children with UC when conservative therapy proves to be ineffective.