Appropriate Preconception Corticosteroid-Free Remission Period in Pregnant Women With Ulcerative Colitis.

BACKGROUND: In women with inflammatory bowel disease, at least 3 months of preconception corticosteroid-free remission (CFREM) is recommended by experts in current consensus statements. However, data are lacking on the appropriate preconception remission period. We investigated the appropriate preconception CFREM period in women with ulcerative colitis to reduce maternal disease activity and adverse pregnancy outcomes (ie, preterm birth, low birth weight, and small for gestational age). METHODS: We retrospectively examined 141 pregnancies in women with ulcerative colitis at 2 institutions. We categorized the patients into 3 subgroups by their preconception CFREM period (≥3 months, >0 to <3 months, and non-CFREM). We also investigated disease activity during pregnancy and postpartum and adverse pregnancy outcomes in each group. RESULTS: During pregnancy, the rate of active disease was significantly lower in the ≥3 months and >0 to <3 months CFREM groups compared with that in the non-CFREM group (P < .001 and P = .0257, respectively). Postpartum, the rate of active disease was significantly lower in the ≥3 months CFREM group compared with that in the non-CFREM group (P = .0087). The preconception CFREM period of ≥3 months was an independent inhibitory factor for active disease during pregnancy and postpartum (adjusted odds ratio, 0.15; P = .0035; and adjusted odds ratio, 0.33; P = .027, respectively). Adverse pregnancy outcomes were less common in the >3 months CFREM group compared with those in the other groups, but this difference was not significant. CONCLUSIONS: A preconception CFREM period of more than 3 months may be appropriate for better maternal and adverse pregnancy outcomes, as recommended in consensus statements.

In women with ulcerative colitis, a preconception corticosteroid-free remission period for at least 3 months may be appropriate. This period could reduce disease activity during pregnancy and postpartum and reduce the incidence of adverse pregnancy outcomes.

Fulminant Amebic Enteritis in the Perinatal Period.

Pregnancy is a known risk factor for amebic enteritis, which develops into potentially fatal fulminant amebic enteritis in some cases. We describe a case of a 27-year-old non-immunosuppressed pregnant woman with fulminant amebic enteritis complicated with cytomegalovirus enteritis. She improved with intensive care and intravenous metronidazole and ganciclovir but eventually required subtotal colectomy for intestinal stenosis. It is difficult to diagnose amebic enteritis, especially in a non-endemic area. Amebic enteritis must be considered as a differential diagnosis for refractory diarrhea with bloody stools in women in the perinatal period, even those without immunosuppression.

[Surgical ulcerative colitis complicated by multiple lung abscesses secondary to septic pulmonary embolism after multidrug immunosuppressive therapies].

This is a case implying a serious infectious complication risk during intensive severe ulcerative colitis treatment. A 26-year-old man developed diarrhea and bloody stool who was diagnosed with ulcerative colitis in 2018. He was managed with 5-aminosalicylic acid, but intolerance reaction resulted in discontinuation of treatment. He relapsed with severe abdominal pain and bloody stools in February 2019. He was referred to our department for intensive therapy. He had been treated with steroids, tacrolimus, granulocyte and monocyte apheresis, infliximab or tofacitinib, which temporarily improved his clinical symptoms. However, his medical condition could not be controlled. Hand-assisted laparoscopic subtotal colectomy was then performed in October 2019. He developed intermittent fever on postoperative day 3. Enhanced computed tomography (CT) revealed multiple deep vein thromboses and pulmonary embolism. Antibiotics and anticoagulation therapy were initiated, but postoperative day 13 CT showed multiple pulmonary cavities containing fluids and air, which were diagnosed as pulmonary abscess. His intermittent fever was over 38.0°C. Severe cough and hemoptysis lasted 3 weeks, the clinical symptoms and laboratory data then gradually improved after the fourth week.

EGFR inhibition reverses resistance to lenvatinib in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Lenvatinib is approved as a first-line treatment for unresectable HCC. The therapeutic duration of lenvatinib is limited by resistance, but the underlying mechanism is unclear. To establish lenvatinib-resistant cells, Hep3B cells were initially treated with 3 µM lenvatinib. The concentration was gradually increased by 1 µM or 0.5 µM per week and it reached to 7.5 µM 2 months after the initial exposure to lenvatinib. The biological characteristics of these cells were analyzed by ERK activation in the MAPK signaling pathway and a human phospho-receptor tyrosine kinase (RTK) antibody array. Factors possibly related to lenvatinib resistance were analyzed using inhibitors, and cell proliferation was analyzed. We established lenvatinib-resistant HCC cells (LR cells) by long-term exposure to lenvatinib. Lenvatinib reduced ERK activation in the parent cells, but not in the LR cells. RTK array analysis showed that the activities of EGFR and insulin-like growth factor 1 receptor (IGF1R)/insulin receptor (INSR) were significantly increased in LR cells, whereas the activities of other RTKs were unchanged. Erlotinib, a widely used EGFR inhibitor, downregulated ERK activation in LR cells. The proliferation of LR cells will also be affected when lenvatinib is combined with erlotinib to treat LR cells. In contrast, inhibition of IGFR/INSR did not affect ERK activation or cell proliferation. Scavenging of reactive oxygen species (ROS) ameliorated the enhanced EGFR activation in LR cells. Lenvatinib resistance was induced by enhanced EGFR activation, possibly via ROS accumulation, in lenvatinib- resistant cells. These findings may enable the development of lenvatinib combination therapies for HCC.

Consistency of Trans-Abdominal and Water-Immersion Ultrasound Images of Diseased Intestinal Segments in Crohn's Disease.

The aim of this study is to clarify whether trans-abdominal ultrasound (TAUS) can reflect actual intestinal conditions in Crohn's disease (CD) as effectively as water-immersion ultrasound (WIUS) does. This retrospective study enrolled 29 CD patients with 113 intestinal lesions. Five ultrasound (US) parameters (distinct presence/indistinct presence/disappearance of wall stratification in the submucosal and mucosal layers; thickened submucosal layer; irregular mucosal surface; increased fat wrapping around the bowel wall; and fistula signs) that may indicate different states in CD were determined by TAUS and WIUS for the same lesion. Using WIUS as a reference standard, the sensitivity, specificity, and accuracy of TAUS were calculated. The degree of agreement between TAUS and WIUS was evaluated by the kappa coefficient. All US parameters of TAUS had an accuracy >70% (72.6-92.7%). The highest efficacy of TAUS was obtained for fistula signs (sensitivity, specificity, and accuracy values were 63.6%, 96.0%, and 92.7%, respectively). All US parameters between TAUS and WIUS had a definitive (p ≤ 0.001) and moderate-to-substantial consistency (kappa value = 0.446-0.615). The images of TAUS showed substantial similarity to those of WIUS, suggesting that TAUS may function as a substitute to evaluate the actual intestinal conditions of CD.