Association of CD4-positive cell infiltration with response to vedolizumab in patients with ulcerative colitis.

Not all patients with ulcerative colitis (UC) respond initially to treatment with biologic agents, and predicting their efficacy prior to treatment is difficult. Vedolizumab, a humanized monoclonal antibody against alpha 4 beta 7 (α4ß7) integrin, suppresses immune cell migration by blocking the interaction between α4ß7 integrin and mucosal addressin cell adhesion molecule 1. Reports about histological features that predict vedolizumab efficacy are scarce. So, we examined the association between histological features and vedolizumab efficacy. This was a multicenter, retrospective study of patients with UC treated with vedolizumab. Biopsy specimens taken from the colonic mucosa prior to vedolizumab induction were used, and the areas positively stained for CD4, CD68, and CD45 were calculated. Clinical and histological features were compared between those with and without remission at week 22, and the factors associated with clinical outcomes were identified. We enrolled 42 patients. Patients with a high CD4+ infiltration showed a better response to vedolizumab [odds ratio (OR) = 1.44, P = 0.014]. The concomitant use of corticosteroids and high Mayo scores had a negative association with the vedolizumab response (OR = 0.11, P = 0.008 and OR = 0.50, P = 0.009, respectively). Histological evaluation for CD4+ cell infiltration may be helpful in selecting patients who can benefit from vedolizumab.

Clinical outcome of conservatively managed pancreatic intraductal papillary mucinous neoplasms with mural nodules and main duct dilation.

BACKGROUND: Surgical resection of intraductal papillary mucinous neoplasm (IPMN) is strongly recommended for patients exhibiting high-risk stigmata (HRS). However, determining surgical indications for elderly patients with comorbidities is challenging, as clinical outcomes are not well characterized. This multicenter observational study elucidated the clinical outcomes of patients with IPMN exhibiting HRS who did not undergo surgery. METHODS: This study enrolled 101 IPMN patients exhibiting HRS with follow-up observations at 11 hospitals in Japan (2011-2016). The median observation period was 37 months (maximum: 86 months). Primary outcomes were estimated 5-year overall survival (OS) and disease-specific survival (DSS). Survival was also stratified based on HRS features. RESULTS: Of 101 patients, 32 (31.7%) had the main pancreatic duct (MPD) measuring ≥ 10 mm and 80 (79.2%) had mural nodules measuring ≥ 5 mm. The estimated 5-year OS and DSS were 74% and 91%, respectively. In the stratified analysis, the co-presence of MPD ≥ 10 mm and mural nodules ≥ 5 mm or mural nodule ≥ 10 mm were related to worse 5-year DSS (MPD ≥ 10 mm and mural nodules ≥ 5 mm vs other characteristics: 60% vs 95%, log-rank test: p = 0.049; mural nodules ≥ 10 mm vs < 10 mm: 77% vs 95%, log-rank test: p = 0.003). CONCLUSIONS: The estimated 5-year DSS of conservatively managed IPMN patients with mural nodules and main duct dilation was 91%. Only IPMN patients with plural HRS or large nodule formation might have an increased mortality risk. This is an important insight that can help facilitate appropriate clinical decision-making, especially in the elderly or high-surgical risk IPMN patients.

Diagnostic significance of gently sloping depression and irregular margin in superficial elevated colorectal tumors.

INTRODUCTION: Recently, superficial elevated colorectal tumors have been increasingly diagnosed after improvements in endoscopic instruments and techniques. However, their biological characteristics remain obscure and it is difficult to predict malignant potential. The aim of this study is to clarify the characteristics of superficial elevated tumors in endoscopic examination for the evaluation of malignant potential. MATERIALS AND METHODS: Sixty-three resected superficial elevated colorectal tumors more than 10 mm in diameter were analyzed with regard to their morphological characteristics and histological findings. The samples were classified according to the presence of a gently sloping depression and irregular margin at the edge. Their depth of vertical invasion and the degree of depression were examined. RESULTS: The rate of carcinoma in 27 lesions with a gently sloping depression was significantly higher than in 36 lesions with an even surface. The rate of carcinoma in 46 lesions with irregular margin was significantly higher than in 17 lesions without irregular margin. A multivariate analysis revealed that the coexistence of both IM and GSD was significantly associated with submucosal invasion. Statistical associations of age, tumor location, gender, and pathological grade with submucosal invasion were not observed. CONCLUSIONS: In superficial elevated colorectal tumors, a gently sloping depression and irregular margin at the edge when viewed endoscopically may be a predictor of malignant potential. These characteristics should be given priority when deciding on treatment.

Leukocytapheresis therapy for steroid-naïve patients with active ulcerative colitis: its clinical efficacy and adverse effects compared with those of conventional steroid therapy.

BACKGROUND: Steroid administration currently plays a central role in the medical management of ulcerative colitis (UC); however, long-term steroid usage causes adverse effects, which necessitates stoppage of drug intake, leading to worsening of the disease. A steroid-sparing, well-tolerated treatment is therefore required. As several investigators have reported the efficacy of leukocytapheresis (LCAP) combined with steroid therapy, we investigated the clinical usefulness and safety of LCAP for steroid-naïve patients with active UC for comparison with those of conventional steroid therapy. METHODS: Twenty-nine Japanese patients with active UC without a history of steroid usage were selected to be treated with LCAP (n = 9) or prednisolone (PSL) (n = 20). LCAP administration continued for 10 weekly cycles. In the PSL group, patients with moderately severe disease received 0.5 mg/kg per day of PSL and those with severe disease 1.0 mg/kg per day. The PSL dosage was gradually tapered in accordance with improvement. RESULTS: Eight (88.9%) of the LCAP group and 16 (80.0%) of the PSL group showed clinical improvement and three (33.3%) of the LCAP group and seven (35.0%) of the PSL group achieved remission. As for the treatment complications, three major adverse effects were observed in the PSL group, but none were observed in the LCAP group. CONCLUSION: The results of this study suggest that the efficacy and safety of LCAP are equivalent, and in terms of severe adverse effects, superior to those of steroid therapy. LCAP therapy may thus be a promising candidate therapy for steroid-naïve patients with active UC.

Chemosensitivity assessed by collagen gel droplet embedded culture drug sensitivity test, and MDR1, MRP1, and MRP2 mRNA expression in human colorectal adenocarcinomas.

PURPOSE: To evaluate chemosensitivity and its correlation with expression levels of the multidrug resistant transporter (MDR1) and the multidrug resistance-associated proteins 1 and 2 (MRP1, MRP2) mRNA in human colorectal adenocarcinomas. METHODS: Colorectal adenocarcinomas were obtained as surgical samples from 25 patients. The chemosensitivity of 12 anticancer drugs was assessed by the collagen gel droplet embedded culture drug sensitivity test (CD-DST). The expression levels of MDR1, MRP1, and MRP2 mRNA in colorectal adenocarcinomas were also evaluated by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The chemosensitivity was successfully evaluated for 16 of 25 patients, and the anticancer drugs were effective against the samples showing a relatively high growth rate. Gemcitabine hydrochloride was found to be more promising than those often prescribed for the treatment of colorectal adenocarcinoma. There was no correlation of the mRNA expression levels of MDR1 and MRP1 with the chemosensitivity of any anticancer drugs tested, but mitomycin C was found to be more effective for the colorectal adenocarcinoma with relatively high expression of MRP2 mRNA.

MDR1, MRP1 and MRP2 genotypes and in vitro chemosensitivity in Japanese patients with colorectal adenocarcinomas.

In our previous paper, the chemosensitivity of human colorectal adenocarcinoma was evaluated against 12 anticancer drugs including 5-fluorouracil (5-FU), 7-ethyl-10-hydroxycamptothecin (SN-38), mitomycin C (MMC) and cisplatin (CDDP), and it was found that the anticancer drugs were effective against those with a relatively high growth rate. MMC was effective for those with a relatively high mRNA expression of the multidrug resistance-associated protein 2 (MRP2), whereas no correlation was found for the multidrug resistant transporter MDR1 and MRP1. In this study, 3 genotypes of MDR1, 4 genotypes of MRP1, and 6 genotypes of MRP2 were additionally evaluated, and it was suggested that MDR1 C3435T and MRP2 G1249A were related with the susceptibility to colorectal adenocarcinoma. The chemosensitivity against 5-FU, SN-38, MMC and CDDP was independent of MDR1 C3435T, MRP1 G2168A, and MRP2 C-24T (C3972T), possibly due to no association with the growth rate of and mRNA expression levels of MDR1, MRP1 and MRP2 in the adenocarcinoma, however, MDR1 C3435T tended to be accompanied with a higher expression of MDR1 mRNA.