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Background and aims: Crohn's disease (CD)‐associated intestinal cancers are characterized by their high incidence, particularly at the anorectal site in the Japanese population. Accumulating evidence revealed that younger‐onset sporadic colorectal cancer may exhibit unique biological features. To the best of our knowledge, few previous articles reported clinicopathological features in patients with CD‐associated anorectal cancer (CDAAC). Therefore, we aimed to clarify the relationship between the younger onset of cancer and clinicopathological characteristics and prognosis, and the efficacy of cancer surveillance in patients with CDAAC. Methods: CD patients who had been diagnosed with intestinal cancers from 1983 to 2020 were collected from 39 Japanese institutions in this study. Of 316 patients with CD‐associated intestinal cancers, we analyzed 211 patients with CDAAC. We divided the patients into two groups according to the median age at cancer diagnosis (45 years old). Results: Younger‐onset CDAAC (YO‐CDAAC) patients were significantly more likely to have a poor outcome than those with older‐onset CDAAC (OO‐CDAAC) in terms of both disease‐free survival (DFS) (p = 0.0014) and overall survival (OS) (p = 0.023). Multivariate analysis showed that age under 45 years old at diagnosis of cancer was one of the independent factors for poor DFS and OS (hazard ratios: 2.15, 95% confidence interval: 1.09–4.26, p = 0.028, hazard ratios: 1.95, 95% confidence interval: 1.05–3.60, p = 0.033, respectively). Patients detected via surveillance showed significantly better DFS and OS rates than symptomatic patients in YO‐CDAAC (p = 0.012 and 0.0031, respectively). Conclusions: YO‐CDAAC may have a poorer prognosis compared with OO‐CDAAC. Surveillance could be important to improve cancer prognosis, especially in young CD patients with anorectal disease. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) and hypokalaemia are common adverse events after treatment with liposomal amphotericin B (L‐AMB). Objectives: Because excess potassium (K) leakage occurs during renal tubular injury caused by L‐AMB, measuring the decrease in rate of serum K concentration might be more useful to assess the renal impact of L‐AMB than hypokalaemia identified from a one‐point measurement. The effects of a decrease in K concentration and duration of hypokalaemia on AKI were investigated. Methods: A ≥ 10% decrease in K concentration from the reference concentration within a 7‐day timeframe was evaluated. The hypokalaemia index, which combines the duration of K concentration lower than the reference and a marked low K concentration, was calculated from the area over the concentration curve. Results: Eighty‐six patients were included in the study. The incidences of AKI and decrease in K concentration were 36.0% and 63.9%, respectively. Of patients who developed both adverse events, a decrease in K concentration occurred first in 22 of 26 patients, followed by AKI 7 days later. Hypokalaemia did not increase AKI risk whereas a decrease in K concentration was an independent risk factor for AKI. The hypokalaemia index in patients with AKI was significantly higher than those without AKI (5.35 vs. 2.50 points, p = 0.002), and ≥3.45 points was a significant predictor for AKI. Conclusion: A ≥ 10% decrease in the K concentration was a significant factor for AKI in patients receiving L‐AMB therapy. In such patients, dose reduction or alternative antifungals could be considered based on the hypokalaemia index. [ABSTRACT FROM AUTHOR]

Background and Aim: Colitis‐associated intestinal cancer (CAC) can develop in patients with inflammatory bowel disease; however, the malignant grade of CAC may differ from that of sporadic colorectal cancer (CRC). Therefore, we compared histological findings distinct from cancer stage between CAC and sporadic CRC to evaluate the features of CAC. Methods: We reviewed the clinical and histological data collected from a nationwide database in Japan between 1983 and 2020. Patient characteristics were compared to distinguish ulcerative colitis (UC), Crohn's disease (CD), and sporadic CRC. Comparisons were performed by using all collected data and propensity score‐matched data. Results: A total of 1077 patients with UC‐CAC, 297 with CD‐CAC, and 136 927 with sporadic CRC were included. Although the prevalence of well or moderately differentiated adenocarcinoma (Tub1 and Tub2) decreased according to tumor progression for all diseases (P < 0.01), the prevalence of other histological findings, including signet ring cell carcinoma, mucinous carcinoma, poorly differentiated adenocarcinoma, or squamous cell carcinoma, was significantly higher in CAC than in sporadic CRC. Based on propensity score‐matched data for 982 patients with UC and 268 with CD, the prevalence of histological findings other than Tub1 and Tub2 was also significantly higher in those with CAC. At pT4, mucinous carcinoma occurred at a significantly higher rate in patients with CD (45/86 [52.3%]) than in those with sporadic CRC (13/88 [14.8%]) (P < 0.01). Conclusion: CAC, including early‐stage CAC, has a higher malignant grade than sporadic CRC, and this difference increases in significance with tumor progression. [ABSTRACT FROM AUTHOR]

Background: The overall risk of colorectal cancer in Crohn's disease (CD) is higher than in the general population, and CD‐associated cancer (CDAC) has poorer prognosis than sporadic cancer. Developing treatment strategies for improving the prognosis of CDAC, we evaluated the characteristics of CDAC according to the underlying disease behavior, namely stricturing and penetrating. Methods: This multicenter retrospective study comprises 316 CDAC patients who underwent surgery between 1985 and 2019. Clinicopathological findings including disease behavior and oncological outcomes were investigated. Results: There was no association between the preoperative course of CDAC patients and disease behavior; however, postoperative information revealed distinctly different characteristics between CDAC patients with stricturing behavior and those with penetrating behavior (stricturing with lymphatic invasion and peritoneal dissemination recurrence, and penetrating with histologically poorly differentiated and local recurrence). Oncological outcome of patients with CDAC was distinctly different according to disease behavior, as penetrating provided a poor outcome (overall survival [OS]: p = 0.02; relapse‐free survival [RFS]: p = 0.002) whereas stricturing had no effect. Furthermore, penetrating behavior was identified as one of the independent risk factors for poor OS and RFS (OS: hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.16–3.09, p = 0.01; RFS: HR 2.15, 95% CI 1.28–3.63, p = 0.004). Conclusions: Our study highlights the different characteristics of CDAC according to the underlying disease behavior and substantiates the poor prognosis of CDAC patients with penetrating behavior. Treatment planning including screening, surgical procedures, and postoperative treatment, with awareness of these findings, may contribute to improved prognosis for CDAC patients. [ABSTRACT FROM AUTHOR]

Aim: The purpose of this study was to examine how the clinical characteristics, indications for surgery, and postoperative course of ulcerative colitis (UC) surgical patients changed before and after the introduction of biological agents. Methods: Patients who underwent surgery for UC at Hyogo Medical University between 2000 and 2019 were included in the study; those who underwent surgery between 2000 and 2009 were included in the early group (n = 864), and those who underwent surgery between 2010 and 2019 were included in the late group (n = 834); each study factor was retrospectively compared. Results: The mean ages at surgery (y) were 39.7 ± 15.1 y in the early group and 46.7 ± 17.8 y in the late group (P <.01). Antitumor necrosis factor agents were used (%) in 2 (0.2) patients in the early group and 317 (38.0) patients in the late group (P <.01). The number of cancer or dysplasia patients for whom surgery was indicated was significantly higher in the late group (11%/26%, P =.01). With regard to surgery in elderly individuals, the number of elderly patients (65 y and older) undergoing surgery was significantly higher in the late group (8.0%/18.6%, P <.01). For emergency surgery, the mortality rates were 16.7% (2/12) in the early surgery group and 15.7% (8/51) in the late surgery group (P =.61). Conclusion: The characteristics of UC patients requiring surgery in Japan have changed. The distribution of surgical indications changed, and the number of patients with cancer and dysplasia requiring surgery increased. The prognosis of elderly patients who underwent emergency surgery was poor. [ABSTRACT FROM AUTHOR]

Background and aim: Ustekinumab (UST), a fully humanized monoclonal antibody against the p40 subunit of interleukin‐12/23, is effective for the treatment of Crohn's disease (CD). The benefit of concomitant use of an immunomodulator (IM) with UST, however, is unclear. This study aimed to provide a systematic review and meta‐analysis comparing the efficacy and safety of concomitant use of an IM with UST as an induction therapy for CD patients. Methods: A systematic literature search was performed using PubMed/MEDLINE, the Cochrane Library, and the Japana Centra Revuo Medicina from inception to October 31, 2019. The main outcome measure was achievement of clinical efficacy (remission, response, and clinical benefit) at 6–12 weeks. The quality of the included studies was assessed using the risk of bias in non‐randomized studies of interventions (ROBINS‐I) tools. The fixed‐effects model was used to calculate the pooled odds ratios. Results: From 189 yielded articles, six including a total of 1507 patients were considered in this meta‐analysis. Concomitant use of an IM with UST was significantly effective than UST monotherapy as an induction therapy (pooled odds ratio in the fixed‐effects model: 1.35, 95% confidence interval [1.06–1.71], P = 0.015). The heterogeneity among studies was low (I2 = 2.6%). No statistical comparisons of the occurrence of adverse events between UST monotherapy and concomitant use of an IM with UST were performed. Conclusion: The efficacy of concomitant use of an IM with UST as an induction therapy for CD was significantly superior to that of monotherapy with UST. [ABSTRACT FROM AUTHOR]

Background and Aim: Anti‐tumor necrosis factor (TNF) α agents are now well known to function as effective treatments for Crohn's disease (CD). Several meta‐analyses have revealed the efficacy of anti‐TNF therapy for preventing recurrence after surgery; however, the efficacies reported in some prospective studies differed according to the outcomes. Moreover, adverse events (AEs) were not well evaluated. We conducted this systematic review and meta‐analysis to evaluate both the efficacy of anti‐TNF therapy after stratification by the outcome of interest and the AEs. Methods: We performed a systematic literature review of studies investigating anti‐TNF therapy, CD, and postoperative recurrence. Meta‐analyses were performed for endoscopic and clinical recurrence and AEs. Results: A total of 570 participants, including 254 patients in the intervention group and 316 patients in the control group, in eight studies, were analyzed for recurrence. Based on the results of the meta‐analysis, the efficacies of anti‐TNF therapy at preventing endoscopic and clinical recurrence were as follows: relative risk (RR) 0.34, 95% confidence interval (CI) 0.22–0.53 and RR 0.60, 95% CI 0.36–1.02, respectively. The RR of AEs with anti‐TNF therapy was 1.75 (95% CI 0.81–3.79). Conclusions: Anti‐TNF therapy after surgery for CD displays efficacy at preventing endoscopic recurrence for 1–2 years, without increasing the incidence of AEs. However, clinical recurrence was not significantly reduced. The efficacy of postoperative anti‐TNF therapy may differ in terms of the outcomes, which include long‐term prevention, the avoidance of further surgery, and cost‐effectiveness. [ABSTRACT FROM AUTHOR]

Background and Aim: Although surveillance colonoscopy is recommended by several guidelines for Crohn's disease (CD), the evidence is insufficient to support the validity of this recommendation. Moreover, the efficacy of surveillance colonoscopy for anorectal cancer remains unclear. Therefore, we performed a systematic review of cancer in patients with CD before considering the proper surveillance methods. Methods: We conducted a systematic review and meta‐analysis examining the incidence of intestinal cancer and a literature review to clarify the characteristic features of cancer in CD. We performed the systematic literature review of studies published up to May 2019. Results: Overall, 7344 patients were included in eight studies. The standardized incidence ratios (95% confidence intervals) of colorectal cancer (CRC) and small bowel cancer (SBC) were 2.08 (1.43–3.02) and 22.01 (9.10–53.25), respectively. The prevalence of CRC and SBC was 57/7344 (0.77%) and 17/7344 (0.23%), respectively, during a median follow‐up of 12.55 years. Additionally, 54 studies reporting 208 anorectal cancer cases were identified. In patients with anorectal cancer, the prognosis for survival was 2.1 ± 2.3 years, and advanced cancer greater than stage T3 occurred in 46/74 patients (62.1%). Many more reports of anorectal cancer were published in Asia than in Western countries. Conclusion: Although we were unable to state a recommendation for surveillance for SBC, we should perform cancer surveillance for CRC in patients with CD. However, the characteristics of cancer may differ according to geography or race. We must establish proper and effective surveillance methods that are independently suitable to detect these differences. [ABSTRACT FROM AUTHOR]

Summary: Background: Hepatotoxicity and visual symptoms are common adverse effects (AEs) of voriconazole therapy. Objective: To retrospectively evaluate the effects of treatment modification based on therapeutic drug monitoring on AEs in patients undergoing voriconazole therapy. Methods: The target voriconazole trough concentration (Cmin) was 1‐5 µg/mL. Receiver operating characteristic curves were used to determine Cmin cut‐offs for AEs. Results: A total of 401 patients were included. Among 108 patients with high initial Cmin, voriconazole was discontinued in 32 and the dose was reduced in 71. Among 44 patients with low initial Cmin, voriconazole was discontinued in 4 and the dose was increased in 19. Hepatotoxicity occurred in 6.0% of patients, after a median of 10 days. Visual symptoms were evident in 9.5% of patients after a median of 4 days. Initial Cmin was significantly associated with visual symptoms but not hepatotoxicity, which suggested the effect of treatment modification on hepatotoxicity. However, both hepatotoxicity and visual symptoms were significantly correlated with Cmin at the onset of AEs, and the Cmin cut‐offs were 3.5 μg/mL for hepatotoxicity and 4.2 μg/mL for visual symptoms. Voriconazole was discontinued after the occurrence of AEs in 62.5% of patients with hepatotoxicity but only 26.3% of patients with visual symptoms. With dose adjustment, treatment was completed in 8/9 patients with hepatotoxicity and 27/28 patients with visual symptoms. Conclusions: A significant preventive effect was demonstrated on hepatotoxicity, but not on visual symptoms because of earlier occurrence. With treatment modification after the occurrence of AEs, most patients completed therapy. [ABSTRACT FROM AUTHOR]

Background: Intensive glycemic control is recommended to prevent surgical site infections (SSI). Our aim was to evaluate retrospectively the effect of improvement in hyperglycemia irrespective of insulin use on the incidence of SSI in non-diabetic patients. Methods: The highest blood glucose (BG) concentration within 12 h (early peak BG) and the final BG from 12 to 24 h after surgery were evaluated in patients who underwent gastrointestinal surgery. Patients with an early peak BG of ≥150 mg/dL were divided into those with persistent (final BG of ≥150 mg/dL) and improved hyperglycemia (final BG of <150 mg/dL). Patients without hyperglycemia and those with late-onset hyperglycemia were also assessed for SSI risk. Results: Overall, 1612 patients were studied (diabetes, n = 293). Although hyperglycemia increased the SSI rates in non-diabetic patients, no correlation was demonstrated in patients with diabetes at any cutoff final BG defining htperglycemia except for 180 mg/dL. Hyperglycemia improved without insulin therapy in 283 of 512 non-diabetic patients who had early hyperglycemia. The adjusted standardized residual for those with SSI and persistent hyperglycemia was 5.2 (P < 0.05). In contrast, the absence of hyperglycemia was a significant preventive factor for SSI. In the multivariate analyses, persistent hyperglycemia was an independent risk factor for SSI (odds ratio 1.54; 95% confidence interval 1.03–2.31). Conclusions: Remission of hyperglycemia within 24 h after surgery prevented SSI in non-diabetic patients. Considering that hyperglycemia improved in approximately half of patients without insulin therapy, commencement of insulin dosing after two consecutive BGs of ≥150 mg/dL might be reasonable, especially in general wards. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study was to develop a risk calculator predictive of postoperative pneumonia in patients undergoing gastroenterological surgery. Methods: We analyzed data from 382 124 patients undergoing eight main gastroenterological surgeries between 2011 and 2013 using the National Clinical Database in Japan. A risk model was developed using multivariate logistic regression analysis with patient data from 2011 to 2012 (n = 247 604) and validated using data from 2013 (n = 134 520). Results: Pneumonia was observed in 11 105 patients (2.9%). After the input of significant primary disease and surgical procedures, 18 patient characteristics including gender, chronic obstructive pulmonary disease, sepsis, and need for any assistance in the activities of daily living, six laboratory parameters, and two intraoperative factors were used for risk calculation. Area under the receiver‐operating characteristic curve was 0.822 (95% confidence interval, 0.817‐0.826) in the derivation group and 0.826 (0.819‐0.832) in the validation group. Conclusion: The risk calculator accurately predicted the occurrence of pneumonia following gastroenterological surgery. [ABSTRACT FROM AUTHOR]

Background: Onodera’s prognostic nutritional index (O-PNI) is a well-known predictor of the prognosis of several surgeries. The aim of this study was to evaluate the association between O-PNI and surgical outcome during surgery for ulcerative colitis (UC).Methods: This was a single-institution retrospective cohort study conducted in the Department of Inflammatory Bowel Disease at Hyogo College of Medicine, Japan. The preoperative predictive factors associated with mortality, morbidity, and pouch-related complications (PRCs) were examined separately from surgical procedure.Results: A total of 1151 patients with UC who underwent surgery between January 2000 and December 2015 were included. Total colectomy (TC) alone, ileal pouch-anal anastomosis (IPAA) with ileostomy, and IPAA without ileostomy were performed in 254 patients, 736 patients, and 161 patients, respectively. Mortality and morbidity were found in nine (0.8%) and 320 (27.8%) patients, respectively. The median O-PNI score was 22.6 in patients with mortality and 35.6 in patients without mortality among TC alone (p < 0.01). The significant predictive factors for mortality among TC alone were older age [p = 0.03, odds ratio (OR) 6.8], higher C-reactive protein (p = 0.02, OR 14.5), and O-PNI < 24.9 (p = 0.04, OR 5.6). Among IPAA with ileostomy, an American Society of Anesthesiologists score ≥3 (p = 0.01, OR 2.3), prednisolone (PSL) dosage just before surgery ≥14 mg/day (p = 0.04, OR 1.8), and O-PNI < 35.5 (p < 0.01, OR 2.1) were predictors of PRCs. O-PNI did not predict PRCs among IPAA without ileostomy.Conclusion: Lower O-PNI may predict the prognosis in patients with UC. O-PNI may be a useful indicator for decision-making regarding surgical timing and procedure. [ABSTRACT FROM AUTHOR]

Background: A loop ileostomy is generally created during restorative proctocolectomy (RPC) for treating ulcerative colitis (UC), and an ostomy rod is often used to prevent stoma retraction. However, its usefulness or harmfulness has not been proven. We performed a prospective randomized control study to investigate the non-inferiority of ostomy creation without a rod to prevent stoma retraction. Methods: Patients with UC who underwent RPC were enrolled and randomly divided into groups either with or without ostomy rod use. Incidences of stoma retraction and dermatitis were compared. Results: Of the 320 patients in the study groups, 308 qualified for the intention-to-treat (ITT) analysis, and 257 were included in the per-protocol (PP) analysis. Ostomy retraction was recognized in 6 patients, 3 with a rod and 3 without. The difference with rod use (95% confidence interval) was 0.1 (−2.9 to 3.1)% in the PP analysis and 0.0 (−2.2 to 2.2)% in the ITT analysis. There were no significant differences in stoma retraction regardless of whether an ostomy rod was used in either analysis. Dermatitis was more common in patients with rod use (84/154) than in those without (40/154) ( p < 0.01). Conclusions: Although median body mass indices were extremely low (20 kg/m), an ostomy rod is not routinely needed as it may increase the risk of dermatitis. However, results in obese patients may differ from those shown here, which should be clarified via further studies. [ABSTRACT FROM AUTHOR]

It is generally believed that the accompanying conditions in patients with inflammatory bowel disease (IBD) are associated with a high incidence of surgical site infection (SSI), and sometimes these patients are classified as compromised hosts without definitive clinical evidence. The aim of this study was to clarify the impact of IBD on the occurrence and features of SSI in patients with clean-contaminated wounds. We conducted prospective SSI surveillance of 580 patients with clean-contaminated wounds who underwent surgery between March 2006 and December 2007 using the National Nosocomial Infection Surveillance system. Multivariate analyses using stepwise logistic regression were performed to determine risk factors for SSI. A total of 562 patients with clean-contaminated wounds who underwent surgery for IBD [ulcerative colitis (UC), n = 173; Crohn’s disease (CD), n = 122] or colorectal cancer [(CA), n = 267] were identified for evaluation. SSI was observed in 12.6% of all patients and there was no significant difference in infection rate by type of disease (UC, 14.5%; CD, 13.9%; CA, 10.9%). Multivariate logistic regression analysis yielded an ASA score ≥3 [odds ratio (OR) = 2.04; 95% confidence interval (CI) = 1.06–3.93] and rectal surgery (OR = 2.35; 95% CI = 1.28–4.31) as independent risk factors for SSI. IBD surgery was not an independent risk factor for overall SSI (OR = 1.62; 95% CI = 0.94–2.80). However, there was a significant difference in the incidence of incisional SSI [IBD, 11.9% (UC, 12.7%; CD, 10.7%); CA, 4.9%, p = 0.003]. In the analysis of rectal surgery, the incidence of incisional SSI was 5.3% in CA patients, 12.0% in UC patients, and 26.3% in CD patients. In contrast to overall SSI data, IBD surgery was found to be an independent risk factor for incisional SSI (OR = 2.59; 95% CI = 1.34–5.03). In patients of surgery restricted to clean-contaminated wounds, IBD was shown to be an independent risk factor for incisional SSI. With the use of proper operative procedures and techniques, the incidence of organ/space SSI should not be high in patients who undergo an uncomplicated IBD surgical procedure. [ABSTRACT FROM AUTHOR]