The Comprehensive Complication Index in Ulcerative Colitis: A Comparison with the Clavien-Dindo Classification.

Introduction: The comprehensive complication index (CCI), which weights all postoperative complications according to severity and integrates them into a single formula, has been reported as a new evaluation system. We aimed to compare the CCI with the Clavien-Dindo Classification (CDC) to patients with ulcerative colitis (UC). Methods: Patients who underwent initial surgery for UC from April 2012 to March 2020 were included. The patients were classified into a length of stay (LOS) >30 days group or an LOS ≤30 days group. We performed a multivariate analysis of risk factors for LOS >30 days in the model with the factors identified in the univariate analysis plus the CCI (the CCI model) and plus CDC (the CDC model). An ROC curve was used to test the difference in the area under the curve (AUC) between the CCI model and the CDC model. Results: The median LOS was 21 days (IQR: 16-29 days), and the rate of LOS >30 days was 119/588 (20.2%). In the CCI model, age at the time of surgery (odds ratio [OR] = 1.24, 95% confidence interval [CI] 1.07-1.45, p = 0.01), ASA score ≥3 (OR = 1.94, 95% CI:1.00-3.76, p = 0.04), and CCI (OR = 1.07, 95% CI: 1.05-1.09; p < 0.01) were identified as independent risk factors for LOS >30 days. The AUC value of the CCI model (0.86) was significantly better in relation to LOS >30 days than that of the CDC model (0.82) (p = 0.02). Conclusion: The CCI was a better measure of LOS than was the CDC and was found to be a useful indicator in UC.

The Impacts of Laparoscopic Restorative Proctocolectomy for Ulcerative Colitis: Systematic Review and Meta-Analysis.

Introduction: Laparoscopic surgery (LAP) is now recognized as the standard procedure for colorectal surgery. However, the standard surgery for ulcerative colitis (UC) is total proctocolectomy with ileal pouch anal anastomosis (IPAA), which may be an overly complex procedure to complete laparoscopically. We conducted this systematic review and meta-analysis to evaluate the efficacy as well as the advantages and disadvantages of LAP-IPAA in patients with UC stratified by the outcome of interest. Method: We performed a systematic literature review by searching the PubMed/MEDLINE, the Cochrane Library, and the Japan Centra Reuvo Medicina databases from inception until January 2023. Meta-analyses were performed for surgical outcomes, including morbidity and surgical course, to evaluate the efficacy of LAP-IPAA. Results: A total of 707 participants, including 341 LAP and 366 open surgery (OPEN) patients in 9 observational studies and one randomized controlled study, were included. From the results of the meta-analyses, the odds ratio (OR) of total complications in LAP was 1.12 (95% CI: 0.58-2.17, p = 0.74). The OR of mortality for LAP was 0.38 (95% CI: 0.08-1.92, p = 0.24). Although the duration of surgery was extended in LAP (mean difference (MD) 118.74 min (95% CI: 91.67-145.81), p < 0.01) and hospital stay were not shortened, the duration until oral intake after surgery was shortened in LAP (MD -2.10 days (95% CI: -3.52-0.68), p = 0.004). Conclusions: During IPAA for UC, a similar morbidity rate was seen for LAP and OPEN. Although LAP necessitates extended surgery, there may be certain advantages to this procedure, including easy visibility during the surgical procedure or a shortened time to oral intake after surgery.

Histological differentiation between sporadic and colitis-associated intestinal cancer in a nationwide study: A propensity-score-matched analysis.

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.

Associations between Pouchitis and Fecal Calprotectin after Restorative Proctocolectomy in Patients with Ulcerative Colitis.

Introduction: Recently, fecal calprotectin has been identified and used as an assessment tool for the confirmation of disease activity in ulcerative colitis. Although a meta-analysis suggested the usefulness of fecal calprotectin for the assessment of pouchitis, the number of participants was still insufficient. Therefore, we prospectively measured fecal calprotectin levels during pouchoscopy and analyzed their associations with pouchitis. Methods: Patients who underwent pouchoscopy after total proctocolectomy and ileal pouch-anal anastomosis for ulcerative colitis were included. Fecal samples were collected for the measurement of calprotectin during pouchoscopy. Patients either with or without suspicious pouchitis were included. Pouchitis was defined as a modified pouchitis disease activity index (m-PDAI) score of ≥5. The associations between the development of pouchitis and the m-PDAI score and fecal calprotectin and serum markers, including C-related protein, albumin, and white blood cells, were assessed. Results: A total of 170 patients were included. Seventy-two patients were diagnosed with pouchitis with an m-PDAI score of 7.3 ± 1.5. The values of fecal calprotectin were 1,500 ± 1,544 µg/g in patients with pouchitis and 259 ± 402 µg/g in patients without pouchitis (p < 0.01). The correlation coefficient between calprotectin and the m-PDAI score was significant (r2 = 0.279, p < 0.001). The cutoff value of fecal calprotectin in receiver operating characteristic analysis was 246 µg/g (area under curve 0.85, sensitivity 83.9%, specificity 71.0%). Fecal samples were able to be collected from 6 patients. The levels of fecal calprotectin significantly decreased from 2,101.3 ± 880.3 µg/g to 284.2 ± 96.9 µg/g in response to the treatment. Conclusions: Elevated fecal calprotectin appeared to be significantly correlated with pouchitis. We should consider the alteration of this marker during treatments in further studies.

Clinical features and surgical selection in colitis-associated colorectal cancer with ulcerative colitis.

PURPOSE: The aim of this study was to compare the clinical characteristics of ulcerative colitis (UC) patients who underwent surgery for cancer/dysplasia with those who underwent surgery for refractory disease and to discuss the preoperative preparation for successful hand-sewn IPAA. METHODS: Patients who underwent surgery for UC between January 2014 and December 2021 at Hyogo Medical University were included in the study. A total of 443 UC surgical cases were included in the study, which comprised 188 cancer/dysplasia patients and 255 refractory patients. Clinical records were compared retrospectively. RESULTS: The proportion of surgical UC cases with cancer/dysplasia has been on the rise, accounting for approximately 40% in recent years. The duration of disease (months) was 186 (2-590) in the cancer/dysplasia group and 48 (1-580) in the refractory group (p = 0.02). UC severity (mild/moderate/severe) was 119/69/0 in the cancer/dysplasia group and 18/157/80 in the refractory group (p < 0.01). The four nutrition factors of weight (55.2 (32.7-99.6) kg: 49.9 (20.3-85.2) kg), body mass index (21.0 (13.9-32.5) kg/m2: 18.3 (11.4-34.1)kg/m2), serum albumin level (4.3 (2.7-5.0)g/dl: 3.4 (1.4-5.2)g/dl) and prognostic nutrition index (49.2 (33.2-61.2): 40.9 (17.4-61.1)) were significantly higher in the cancer/dysplasia group (p < 0.01). The degree of obesity was also significantly higher in the cancer/dysplasia group (p < 0.01). CONCLUSION: UC patients with cancer/dysplasia were more likely than refractory patients to have mild inflammation; they also had a longer duration of UC disease and better nutritional status.

[Questionnaire Survey on the Timing of Comprehensive Genomic Profiling for Advanced Recurrent Colorectal Cancer and Its Impact on Patients].

BACKGROUNDS: Comprehensive genomic profiling(CGP)has been covered by health insurance since June 2019. However, the clinical impact of CGP on patients with metastatic colorectal cancer(mCRC)remains unclear. To date, there are very limited reports regarding patient-oriented outcomes of CGP in mCRC. PATIENTS: A questionnaire was completed by patients with mCRC who had already received their CGP results after April 2021. Eight questions were posed, covering the degree of satisfaction and timing when CGP was conducted. RESULTS: Of the 51 patients with mCRC who had received their CGP test results by August 2021 in our department, 21 patients responded to our questionnaire. In total 66.7% patients with mCRC answered "(very)satisfied"with the CGP testing. 28.6% of the patients already knew about CGP testing before their local doctors informed them. Except for 3 patients who did not answer, 47.6% and 9.5% of patients with mCRC"agreed"and "moderately agreed"with the timing of the CGP test. CONCLUSION: Although most patients with mCRC failed to access promising new treatment via CGP, approximately half of the patients answered that they were satisfied with the CGP testing. Conversely, a few patients already knew about CGP testing before it was proposed by their doctors. Thus, the provision of information at an early stage is necessary.

Anatomical Validation of Internal Iliac Vessels Assessed by Three-dimensional Angiographic Analysis.

Objectives: Anatomical understanding of the internal iliac vessels is important with the increasing frequency of minimally-invasive pelvic surgery. We aimed to investigate the branch patterns of internal iliac vessels, especially the veins. Methods: This study included 30 patients with 60 half-pelvises who underwent minimally-invasive pelvic surgery. Branch patterns were assessed on surgical videos with a multi-detector computed tomography-based three-dimensional simulation. Branch patterns of the superior gluteal artery and vein (SGA and SGV), inferior gluteal artery and vein (IGA and IGV), internal pudendal artery and vein (IPA and IPV), and obturator artery and vein (ObA and ObV) were investigated. Results: In the most frequent internal iliac vein (IIV) branch pattern, 67% of SGV branched from the IIV, 95% of the IGV branched from the IPV and 82% of the ObV branched from the IPV. According to Adachi's classification, 62% of IIVs were Type I and 33% Type IV. Although IIV branch patterns are heterogeneous, in individual patients with the most frequent branch patterns, good correlation (75-100%) of the branch patterns was observed between the internal iliac artery (IIA) and IIV, and between the right and left IIVs. Conclusions: This study clarified the branch patterns of IIV. In patients with the most frequent branch patterns, good correlation of the branch patterns was observed between the IIA and IIV, and between right and left IIV. We believe this helps secure the safety and standardization of minimally-invasive pelvic surgery.

Oncological outcomes of Crohn's disease-associated cancers focusing on disease behavior.

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.

Endoscopic Lesions of Postoperative Anastomotic Area in Patients With Crohn's Disease in the Biologic Era: A Japanese Multi-Centre Nationwide Cohort Study.

BACKGROUND AND AIMS: Many patients have endoscopic evidence of recurrent Crohn's disease [CD] at 1 year after intestinal resection. These lesions predict future clinical recurrence. We endoscopically evaluated postoperative anastomotic lesions in CD patients from a large cohort of postoperative CD patients. METHODS: We retrospectively enrolled CD patients who underwent surgical resection between 2008 and 2013 at 19 inflammatory bowel disease [IBD]-specialist institutions. The initial analyses included patients who underwent ileocolonoscopy ~1 year after intestinal resection. Follow-up analyses assessed any changes in the endoscopic findings over time. We evaluated the postoperative endoscopic findings, which were classified into four categories [no lesion, mild, intermediate, severe] at the sites of the anastomotic line and peri-anastomosis. RESULTS: In total, 267 CD patients underwent postoperative ileocolonoscopy. Postoperative anastomotic lesions were widely detected in index ileocolonoscopy [61.0%] and were more frequently detected in follow-up ileocolonoscopy [74.9%]. Endoscopic severity also increased. Patients with intermediate or severe peri-anastomotic or anastomotic line lesions at the index ileocolonoscopy required significantly more interventions, including endoscopic dilatation or surgery, than patients with mild lesions or no lesions. CONCLUSIONS: Frequent anastomotic lesions were observed at the postoperative index ileocolonoscopy. These gradually increased for subsequent ileocolonoscopy, even in the biologic era. Regarding lesions on the anastomotic line, intermediate lesions on the anastomotic line [e.g. irregular or deep ulcers] might be considered recurrent disease, and mild lesions [e.g. linear superficial ulcers] might be considered non-recurrent disease. Prospective studies are needed to resolve this issue, including treatment enhancement.

Transanal Minimally Invasive Surgical Approach to Total Pelvic Exenteration.

BACKGROUND: Total pelvic exenteration, a surgical procedure for patients with highly advanced primary and recurrent rectal cancer, is technically demanding. IMPACT OF INNOVATION: We report the utility of a transanal minimally invasive surgical approach to total pelvic exenteration. TECHNOLOGY MATERIALS AND METHODS: A 2-team approach with a laparoscopic transabdominal approach and transanal minimally invasive surgery was adopted. During the transabdominal approach in the pelvis, dissection was performed to remove the pelvic organs and visceral branches of the internal iliac vessels. The dissection goal via the transabdominal approach is the levator ani. During the transperineal approach, dissection is performed along the levator ani, and the tendinous arch of the levator ani is penetrated at the lateral side to achieve rendezvous between the 2 approaches. The levator ani is then dissected circumferentially, with identification of the internal pudendal vessels passing through the levator ani at the 4 o'clock and 8 o'clock positions, known as Alcock's canal. The anterior wall of Alcock's canal is formed by the coccygeus muscle and sacrospinous ligament, which are dissected by the transperineal approach to open Alcock's canal, thus obtaining a clear view of the internal pudendal vessels. On the anterior side, the urethra is divided with a laparoscopic linear stapler via the transperineal approach. PRELIMINARY RESULTS: Eight patients with rectal cancer underwent this procedure. The median (range) blood loss was 200 (120-1520) mL and operating time was 467 (321-833) minutes. Reoperation was performed in 1 internal hernia case; however, there were no mortalities, and there were no cases with severe complications or conversion to open surgery. CONCLUSIONS AND FUTURE DIRECTIONS: When performing total pelvic exenteration, transanal minimally invasive surgery offers direct visualization behind the tumor from the anal side and shows the deep pelvic structures, including the retroperitoneal space of the pelvic sidewall.

Risk factors for the postoperative recurrence of ulcerative colitis-associated colorectal cancer.

PURPOSE: Although ulcerative colitis-associated colorectal cancer (UC-CRC) has been described, there are few reports regarding recurrent cases of UC-CRC. In this study, we investigated the risk factors for UC-CRC recurrence. METHODS: Recurrence-free survival (RFS) was determined for 144 stage I to III cancer patients among 210 UC-CRC patients from August 2002 to August 2019. The Kaplan‒Meier method was used to obtain the cumulative RFS rate, and the Cox proportional hazard model was used to extract recurrence risk factors. The interaction term between cancer stage and prognostic factors specific to UC-CRC was evaluated using the Cox model. The Kaplan‒Meier method was applied by cancer stage to the UC-CRC-specific prognostic factors for which interaction effects were indicated. RESULTS: There were 18 cases of recurrence involving patients with stage I to III cancer, and the recurrence rate was 12.5%. The cumulative 5-year RFS rate was 87.5%. Multivariable analysis showed that age at surgery (hazard ratio (HR): 0.95, 95% CI: 0.91-0.99, p = 0.02), undifferentiated carcinoma (HR: 4.42, 95% CI: 1.13-17.24, p = 0.03), lymph node metastasis (HR: 4.11, 95% CI: 1.08-15.69, p = 0.03), and vascular invasion (HR: 8.01, 95% CI: 1.54-41.65, p = 0.01) were significant risk factors for recurrence. Patients with stage III CRC in the young adult (age < 50 years) group had a significantly worse prognosis than those in the adult (age ≥ 50 years) group (p < 0.01). CONCLUSION: Age at surgery was identified as a risk factor for UC-CRC recurrence. Young adult patients with stage III cancer may have a poor prognosis.

[Educational Project of Self-Removal of the Intravenous Central Venous Access Port Guided by Patients with Advanced Colorectal Cancer Instructed by a Nurse in the University Hospital].

BACKGROUND: Fluorouracil infusion for 46±5h from the central venous(CV)port is required for mFOLFOX6, FOLFIRI, and FOLFOXIRI in patients with advanced colorectal cancer(CRC), followed by self-removal of the needle by patients. At our hospital, outpatients were instructed for self-removal of the needle, but the results were unsatisfactory. Therefore, instructions for self-removal of the needle from the CV port have been initiated at the patient ward since April 2019, making use of a hospital stay of 3 days. PATIENTS: We retrospectively enrolled patients with chemotherapy-introduced advanced CRC from the CV port who received instructions for self-removal of the needle in the outpatient department and ward between January 2018 and December 2021. RESULTS: Of all patients with advanced CRC, 21 received instructions at the outpatient department(OP)while 67 at patient ward(PW). Incidences of successful self-removal of the needle without the aid of others were similar: 47% in OP and 52% in PW(p=0.80). However, after several additional instructions involving their families, it was higher in PW than in OP(97.0 vs 76.1%, p=0.005). Incidences of successful self-removal of the needle without the aid of others in those aged≥75/<75, and≥65/<65 years were 0%/61.1%, and 35.4%/67.5%, respectively. OP was as a risk factor for failed self-removal of the needle in the logistic regression analysis(odds ratio: 11.19, 95%CI: 1.86- 67.30). CONCLUSION: Repeated instructions involving patients' families during the hospital stay improved the incidence of successful self-removal of the needle. Involvement of patients' families from the beginning may effectively improve self- removal of the needle, particularly in the elderly patients with advanced CRC.

Erratum forTotal Neoadjuvant Chemotherapy in Rectal Cancer: Current Facts and Future Strategies.

[This corrects the article DOI: 10.23922/jarc.2022-060.].

Short-term clinical evaluation of teduglutide for patients with Crohn's disease on home parenteral support for postoperative short bowel syndrome with intestinal failure.

BACKGROUND & AIM: The short-term effects of teduglutide (TED) for short bowel syndrome with chronic intestinal failure (SBS-IF) in patients with Crohn's disease (CD) remain unknown. The aim of this study was to investigate the effects of TED in patients with CD on home parenteral support (PS) for SBS-IF. METHODS: We retrospectively investigated the medical records of patients with CD associated with SBS-IF who initiated TED between 2020 and 2021. The primary outcomes were the change in PS volume and proportion of patients with a reduction of PS volume by ≥ 20% at week 8. Secondary outcomes were the change in PS volume in patients with CD without/with colon in continuity and adverse events during the observation period. RESULTS: Eighteen patients with CD who underwent home PS for SBS-IF were included in this study. Two patients were excluded owing to intolerable abdominal pain or vomiting within 8 weeks (11%). Sixteen patients continued TED throughout the observation period. The median PS duration was 10.5 years. The median observation period was 22 weeks after starting TED. TED significantly reduced the PS volume from 15,825.0 mL/week to 10,700.0 mL/week (p = 0.0038), and the PS volume decreased by ≥ 20% in 7 patients (43.8%) at week 8. The PS volume was significantly reduced at week 4 (p = 0.0078) in 11 patients without colon in continuity but not in 5 patients with colon in continuity. Two patients successfully stopped home PS. No serious adverse events occurred. CONCLUSIONS: TED administration significantly reduced PS volume at week 8 in patients with CD associated with SBS-IF, and at week 4 in patients without colon in continuity.

Have advances in medical therapy for ulcerative colitis impacted surgical treatment?

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.

Treatment escalation and de-escalation decisions in Crohn's disease: Delphi consensus recommendations from Japan, 2021.

BACKGROUND: We aimed to develop criteria for treatment intensification in patients with (1) luminal Crohn's disease (CD), (2) CD with perianal disease and/or fistula, (3) CD with small bowel stenosis, (4) in the postoperative setting, and (5) for discontinuing or reducing the dose of treatment in patients with CD. METHODS: PubMed and Embase were searched for studies published since 1998 which may be relevant to the five defined topics. Results were assessed for relevant studies, with preference given to data from randomized, controlled studies. For each question, a core panel of 12 gastroenterologists defined the treatment target and developed statements, based on the literature, current guidelines, and relevant additional studies. The evidence supporting each statement was graded using the Oxford Centre for Evidence-Based Medicine: Levels of Evidence (March 2009). A modified Delphi process was used to refine statements and gain agreement from 54 Japanese specialists at in-person and online meetings conducted between October 2020 and April 2021. RESULTS: Seventeen statements were developed for treatment intensification in luminal CD (targeting endoscopic remission), six statements for treatment intensification in perianal/fistulizing CD (targeting healing of perianal lesions and complete closure of the fistula), six statements for treatment intensification in CD with small bowel stenosis (targeting resolution of obstructive symptoms), seven statements for treatment intensification after surgery (targeting endoscopic remission), and five statements for discontinuing or reducing the dose of treatment in patients with CD. CONCLUSIONS: These statements provide guidance on how and when to intensify or de-intensify treatment for a broad spectrum of patients with CD.

Correlation between Antimicrobial Resistance and the Hospital-Wide Diverse Use of Broad-Spectrum Antibiotics by the Antimicrobial Stewardship Program in Japan.

Increased antibiotic use and antibiotic homogeneity cause selective pressure. This study investigated the correlation between antibiotic diversity and antimicrobial resistance (AMR) in Gram-negative organisms. The days of therapy/100 patient-days (DOT) for four broad-spectrum antibiotic classes were evaluated for 2015-2022. The antibiotic heterogeneity index (AHI) for the equal use of four classes (25%) and the modified AHI for the equal use of three classes (30%), excluding fluoroquinolones (10%), were measured (target: 1.0). Quarterly antibiotic use markers and the resistance rates against ≥2 anti-Pseudomonas antibiotics were compared. The DOT value was 9.94, and the relative DOT were 34.8% for carbapenems, 32.1% for piperacillin/tazobactam, 24.3% for fourth generation cephalosporins/ceftazidime/aztreonam, and 8.9% for fluoroquinolones. Although no correlation was found between the total DOT and the resistance rate for any bacterium, a significant negative correlation was found between the heterogeneity indices and resistance rates for Pseudomonas aeruginosa and Klebsiella pneumoniae. The significant cutoffs that discriminate the risk of resistance were 0.756 for the AHI and 0.889 for the modified AHI for K. pneumoniae. Antibiotic diversity is more important in preventing AMR than overall antibiotic use. The ideal ratio of broad-spectrum antibiotics should be studied for diversified use to prevent AMR.

Total Neoadjuvant Chemotherapy in Rectal Cancer: Current Facts and Future Strategies.

Despite preoperative chemoradiotherapy (CRT) and total mesorectal excision improving the local control for locally advanced rectal cancer (LARC), oncologic outcomes and survival were not significantly improved because the main prognostic factor is distant metastasis. Thus, total neoadjuvant chemotherapy (TNT) as a novel approach has been proposed to improve chemotolerance. Since the first randomized phase II trial of TNT versus standard CRT demonstrated in 2012, many prospective and retrospective studies have been published. The initial consensus from TNT studies was that pathological complete response, pathological response of the main tumor, and local control are more favorable at TNT than at CRT. Furthermore, recent studies such as the PAPIDO trial and PRODIGE 23 trial made a major breakthrough of the treatment of TNT, showing that TNT improves the disease-free survival compared to standard treatment with long-course CRT. In addition, several innovative findings of TNT were clarified by prospective phase II trial. In this review, we summarize the most recent advances in TNT based on the findings of pivotal clinical trials for patients with LARC.

Effect of Biologics on the Risk of Advanced-Stage Inflammatory Bowel Disease-Associated Intestinal Cancer: A Nationwide Study.

INTRODUCTION: The aim of this study was to evaluate the effect of biologics on the risk of advanced-stage inflammatory bowel disease (IBD)-associated intestinal cancer from a nationwide multicenter data set. METHODS: The medical records of patients with Crohn's disease (CD) and ulcerative colitis (UC) diagnosed with IBD-associated intestinal neoplasia (dysplasia or cancer) from 1983 to 2020 were included in this study. Therapeutic agents were classified into 3 types: biologics, 5-aminosalicylic acid, and immunomodulators. The pathological cancer stage was compared based on the drug used in both patients with CD and UC. RESULTS: In total, 1,042 patients (214 CD and 828 UC patients) were included. None of the drugs were significantly associated with cancer stage in the patients with CD. In the patients with UC, an advanced cancer stage was significantly associated with less use of biologics (early stage: 7.7% vs advanced stage: 2.0%, P < 0.001), 5-aminosalicylic acid, and immunomodulators. Biologic use was associated with a lower incidence of advanced-stage cancer in patients diagnosed by regular surveillance (biologics [-] 24.5% vs [+] 9.1%, P = 0.043), but this was not the case for the other drugs. Multivariate analysis showed that biologic use was significantly associated with a lower risk of advanced-stage disease (odds ratio = 0.111 [95% confidence interval, 0.034-0.356], P < 0.001). DISCUSSION: Biologic use was associated with a lower risk of advanced IBD-associated cancer in patients with UC but not with CD. The mechanism of cancer progression between UC and CD may be different and needs to be further investigated.