Yokkaichi Social Insurance Hospital

Chronic background mucosal inflammation contributes to colorectal cancer (CRC) development in ulcerative colitis (UC), but its prognostic impact is unclear. We evaluated whether background mucosal inflammation documented at cancer diagnosis is associated with oncologic outcomes. This retrospective study analyzed 1189 UC patients diagnosed with CRC using a nationwide, multicenter database in Japan. Patients were classified as CRC within the UC-involved area (within-area) or outside the UC-involved area (outside-area), based on tumor location relative to the UC disease extent documented endoscopically at cancer diagnosis. The primary end point was 5-year recurrence-free survival (RFS), and the secondary end point was 5-year cancer-specific survival (CSS). In within-area cases, inflammation severity was assessed using the Mayo Endoscopic Score (MES), stratified as Inactive, Mild-Moderate, and Severe. Of the 723 eligible patients, 683 had within-area and 40 outside-area CRC. Five-year RFS was significantly lower in within-area than outside-area CRCs (75.1% vs 87.6%, P = 0.022). Multivariable Cox regression analysis of RFS revealed this classification as an independent prognostic factor (hazard ratio = 2.99, 95% confidence interval: 1.09-8.18, P = 0.030). A significant difference was also observed in 5-year CSS (P = 0.038). Among within-area cases, higher MES was associated with stepwise declines in RFS (P = 0.150), and a similar, statistically significant gradient in CSS (P = 0.048). Background mucosal inflammation at cancer diagnosis is associated with significantly worse prognosis of CRC in UC patients. Systematic endoscopic assessment at cancer diagnosis may aid prognostic stratification and inform management.

To assess, post hoc, tofacitinib safety/effectiveness in patients with ulcerative colitis (UC), stratified by age, using data from a 60-week post-marketing surveillance (PMS) study in Japan. All patients with UC receiving tofacitinib in Japan were enrolled in a large PMS study. Incidence proportions of adverse events (AEs), incidence rates (IRs; unique patients with events/100 patient-years of exposure) of clinically important AEs, reasons for discontinuation, and partial Mayo score clinical remission, stratified by age ( ≥ 65 and < 65 years), were evaluated. The analysis included 212 older ( ≥ 65 years) and 1,770 younger ( < 65 years) patients. Demographics and baseline disease characteristics were generally similar between groups; however, more older versus younger patients had cardiovascular disease (23.1% vs. 4.6%). Incidence proportions of AEs were comparable between groups, but IRs (95% confidence intervals) in older versus younger patients were numerically higher for herpes zoster (9.81 [5.72-15.71] vs. 5.44 [4.28-6.82]), and higher for serious infections (4.45 [1.92-8.76] vs. 1.14 [0.65-1.85]). More older versus younger patients discontinued due to AEs (28.6% vs. 17.6%); more younger versus older patients discontinued due to insufficient clinical responses (50.3% vs. 35.2%). Clinical remission rates through 60 weeks were generally similar between groups. Older patients had higher IRs of herpes zoster and serious infection than younger patients, although tofacitinib effectiveness was similar between age groups. Discontinuation due to AEs was more common in older patients. Despite the smaller sample size of older versus younger patients, a focused evaluation of older patients is of benefit.

In acute myocardial infarction complicated by cardiogenic shock (AMI-CS), low mean arterial pressure (MAP) can reduce cerebral perfusion, potentially resulting in coma. While both MAP and coma on admission are critical prognostic factors, the relationship between them and their prognostic significance based on coma status remains unclear. A retrospective analysis of 543 AMI-CS patients was conducted. The overall median MAP was 77 mmHg, with no significant difference between the coma and non-coma groups. The coma group had a higher 30-day mortality compared with the non-coma group (50% vs. 29%; P<0.001). The area under the curve for MAP predicting 30-day mortality was 0.723 (P<0.001) in the coma group, with a cut-off MAP of 76.3 mmHg (sensitivity 0.66, specificity 0.69), but was insignificant in the non-coma group (AUC 0.543; P=0.176). Kaplan-Meier analysis showed higher mortality with low MAP (<77 mmHg) in the coma group, whereas MAP had no significant impact in the non-coma group. Multivariate Cox regression identified low MAP as an independent prognostic factor in the coma group only. The associations between MAP and prognosis differ depending on the coma status in AMI-CS. Low MAP is a prognostic factor for mortality only in patients with coma. This study highlights the need for treatment strategies tailored to neurological status.

BackgroundUnresectable malignant bile duct stricture (often caused by unresectable pancreatic cancer and cholangiocarcinoma) can be drained via insertion of self-expandable metal stents (SEMS) during endoscopic retrograde cholangiopancreatography (ERCP). Because recurrent biliary obstruction (RBO) and complications following stent insertion can delay chemotherapy and other treatments, a longer time to RBO (TRBO) is desirable. Although a longer TRBO has been reported among patients who undergo insertion with larger diameter SEMS, patients who undergo insertion with smaller diameter fully covered SEMS (FCSEMS) may have a lower incidence of complications than those with larger diameter FCSEMS. The aim of this study is to determine the TRBO and incidence of complications with 6-mm FCSEMS vs 10-mm FCSEMS in patients with unresectable malignant distal bile duct stricture.MethodsIn this multicenter, open-label, randomized controlled, non-inferiority trial (COSMIC UNISON), a target of 250 patients over 23 locations in Japan will receive either the 6-mm FCSEM or the standard 10-mm FCSEM during ERCP, with 125 patients in each group. The observation period will be 24 months, and patients will be enrolled from 15 March 2024 and assessed until the date of RBO or the study end (31 March 2029). The primary endpoint is TRBO, with RBO defined as the coexistence of abnormal liver enzyme values and dilation of the common bile duct and intrahepatic bile duct upstream of the stent. The secondary endpoints are the incidence and rates (at 3, 6, and 12 months) of non-RBO events, overall survival, cause of RBO, and symptomatic stent deviation. Adverse events from endoscopic procedures will be classified by the Lexicon Classification from the American Society of Endoscopy, and all other adverse events will be classified per the Japanese translation of the Common Terminology Criteria for Adverse Events version 5.0.DiscussionThe COSMIC UNISON study is anticipated to provide evidence regarding the efficacy and safety of 6-mm vs 10-mm FCSEMS to inform the use of 6-mm FCSEMS for the treatment of unresectable malignant distal bile duct stricture.Trial registrationJapan Registry of Clinical Trials identifier: jRCT1042230170. Prospectively registered on 15 March 2024.

PurposeFew studies have reported the association of macroscopic classification with clinicopathological characteristics and prognosis of ulcerative colitis-associated colorectal cancer (UC-CRC), unlike sporadic CRC. In this study, we aimed to clarify the clinical significance of macroscopic classification of UC-CRC.MethodsThe cohort included 480 patients with UC-CRC with invasion beyond the muscularis propria treated at 43 Japanese institutions between 1983 and 2023. The patients were divided into six groups based on the macroscopic type (types 0–5), and clinicopathological features and prognoses were compared.ResultsAmong 480 patients, 66 (13.8%), 75 (15.6%), 116 (24.2%), 63 (13.1%), 68 (14.2%), and 92 (19.2%) had type 0–5 tumors, respectively. There were significant differences in the clinicopathological characteristics with a younger age in type 4 or 5 tumors than in type 2 tumors (p < 0.01) and a higher frequency of undifferentiated carcinomas (p < 0.01) and lymph node metastasis (p < 0.01) and more advanced depth of invasion (p < 0.01) in type 4 tumors than in type 1 or 2 tumors. Type 4 and 5 were independent risk factors for 5-year recurrence-free survival (p = 0.02; type 4 [HR: 6.35], type 5 [HR: 5.25]) and type 0, 4, and 5 for overall survival (p = 0.02; type 0 [HR: 4.51], type 4 [HR: 5.70], type 5 [HR: 4.02]).ConclusionsType 0, 4, and 5 tumors were characteristic macroscopic types of UC-CRC and correlated with worse prognosis. Therefore, endoscopic diagnosis of the macroscopic type of UC-CRC might be helpful in determining tumor aggressiveness.

Abstract Background Fistulising perianal diseases (FPD) are common in patients with Crohn's disease (CD) in Asia, but the treatment pattern and the proportion of patients who develop new FPD after diagnosis are not clear. An interim analysis of a large registry study was performed to evaluate the difference in prognosis between patients with and without FPD at diagnosis of CD and the incidence and timing of onset of FPD in patients without FPD at diagnosis of CD. Methods iCREST-CD is a prospective, non-interventional, longitudinal, observational registry study conducted at 19 tertiary centres in Japan. Patients newly diagnosed with CD from June 2016 to June 2020 based on the diagnostic criteria of the Japanese Guidelines, aged ≥16 years at the time of informed consent with no prior exposure to biologics were enrolled. Patient demographics, clinical data, disease activity and medical treatment record up to June 2022 were used. FPD were defined as a perianal abscess and/ or perianal fistula. Results Of the 662 patients with newly diagnosed CD for whom with or without FPD were recorded, 236 patients [35.6%] had FPD at diagnosis (Group A). Of the 426 patients who did not have FPD at the time of diagnosis, 32 patients developed FPD during the observation period (Group B), and 394 patients did not develop it (Group C). The mean age [SD] at the time of CD diagnosis in Groups A, B, and C was 25.0 [8.6], 31.6 [15.5], and 31.7 [14.4] years, respectively. The proportion of female was 21.2%, 34.4% and 37.8%, respectively; L2 disease location was 14.6%, 23.3%, and 18.0%, respectively; and B2+B3 disease behaviour was 27.5%, 53.1%, and 40.6%, respectively. The mean CRP (mg/L [SD]) was 28.5 [33.8], 42.4 [43.6], and 27.1 [36.3], respectively. For disease activity based on HBI score, the proportion with moderate (8≦HBI≦16) and severe (16&amp;lt;HBI) activity was 17.6%, 36.8%, and 24.0%, respectively (Table). The rate of patients who developed FPD was 4.5% (19 patients) by 12 months and 6.5% (28 patients) by 24 months, respectively (Figure). In Group A with a mean observation period (month [SD]) of 27.9 [8.8], 12.3% and 17.3% of patients needed perianal surgery at 12 and 24 months, respectively. In Group B with a mean observation period of 29.7 [7.7], 7 FPD patients [21.9%] subsequently underwent perianal surgery, all within 12 months of FPD onset. Conclusion Patients who did not have a perianal abscess or fistula at the time of their CD diagnosis but later developed these problems tended to have numerically higher CD activity at the time of diagnosis and were more likely to require perianal surgery. These results suggest that patients with highly active CD are at risk of developing new FPD and should be carefully monitored.

Abstract Background Colitis-associated colorectal cancer (CAC) can develop in patients with inflammatory bowel disease, and histological features differ between CAC and sporadic colorectal cancer (CRC). Moreover, advanced CAC has a poorer prognosis than sporadic CRC. Therefore, we compared histopathological findings distinct from cancer stage between CAC and sporadic CRC to evaluate the features of CAC. Methods We reviewed the clinical and histopathological data collected from 43 institutions, including surgery and gastroenterology departments, in the Japanese Society for Cancer of the Colon and Rectum between 1983 and 2020. Patient characteristics were compared between ulcerative colitis (UC), Crohn’s disease (CD), and sporadic CRC. Comparisons were performed by using all collected data or propensity score-matched data. Results A total of 1,077 patients with UC-CAC, 297 with CD-CAC, and 136,927 with sporadic CRC were included in all collected data. Although the prevalence of well or moderately differentiated adenocarcinoma (G1:well differentiated and G2:moderately differentiated) decreased according to tumor progression in all diseases (p&amp;lt;0.01, figure1), the prevalence of G3,G4, including signet ring cell carcinoma, mucinous carcinoma, poorly differentiated adenocarcinoma, neuroendocrine carcinoma and 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 histopathological findings other than G1 and G2 was also significantly higher in CAC (figure2,3). 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&amp;lt;0.01). Conclusion Malignant potential is higher in CAC than in sporadic CRC according to tumor progression, which may lead to the poor prognosis of CAC.

Leucine-rich alpha-2 glycoprotein (LRG) is a novel serum biomarker for inflammation in inflammatory bowel disease (IBD). This prospective study aimed to compare the value of LRG with C-reactive protein (CRP) and fecal calprotectin for evaluating clinical and endoscopic disease activity in patients with IBD. At entry, clinical and endoscopic disease activity was assessed in 267 patients with IBD (ulcerative colitis [UC] 203; Crohn's disease [CD] 64), and the levels of LRG, CRP and fecal calprotectin were measured. The accuracy of the biomarkers for the detection of clinical and endoscopic disease activity was determined by the area under the receiver operating characteristic curve. Leucine-rich alpha-2 glycoprotein showed a significant relationship with the clinical and endoscopic severity in both UC and CD (both diseases, P < .0001). In the clinical assessment of UC, the accuracy of LRG was significantly higher than that of CRP (0.73 vs 0.63; P < .001). In the endoscopic assessment of UC, the accuracy of LRG was significantly higher than that of CRP (P = .01), but it was significantly lower than that of fecal calprotectin (P = .009; LRG, 0.80; CRP, 0.72; fecal calprotectin, 0.91). In the clinical and endoscopic assessment of CD, the accuracy was not significantly different between the biomarkers (clinical activity: LRG, 0.71; CRP, 0.64; fecal calprotectin, 0.66; in endoscopic activity: LRG, 0.79; CRP, 0.78; fecal calprotectin, 0.81). Leucine-rich alpha-2 glycoprotein is a reliable serum biomarker for the assessment of clinical and endoscopic disease activity in patients with IBD. It can be an alternative to CRP for the assessment of UC.

A 79-year-old woman was referred to our hospital complaining of upper abdominal pain. She had no history of diabetes mellitus or other malignant diseases. Blood analysis showed no atypical findings other than elevated levels of CEA and Dupan-2. Contrast-enhanced computed tomography (CT) showed a 50 × 40-mm mass with poor contrast and irregular margins in the head of the pancreas (Fig. 1). Invasion into the superior mesenteric artery and portal vein was also evident. Histopathological examination of a specimen from endoscopic ultrasound-guided fine needle aspiration revealed adenocarcinoma. We diagnosed the mass as locally advanced unresectable pancreatic adenocarcinoma, and decided to perform chemoradiotherapy in order to help control the cancer and slow down its growth. To design radiotherapy, we performed CT on inhalation and free-breathing. The pancreatic mass was on the right side of the spine on inhalation, but surprisingly appeared on the left side of the spine on free-breathing (Fig. 2). We administered radiation at 1.8 Gy/day with fixation of the mass using a body shell and also administered gemcitabine. On day 8 after therapy, the patient developed multiple cerebral infarctions associated with Trousseau syndrome. She subsequently received best supportive care. In general, pancreatic masses have been considered immovable, because the pancreas is fixed to the retroperitoneum with the duodenum. The anterior surface of the pancreas is covered by parietal peritoneum and the inferior border abuts the root of the transverse mesocolon. A loose connective tissue layer, known as the fusion fascia of Treitz in the region of the head of the pancreas and as the fusion fascia of Told in the region of the body and tail, is coherent with the posterior of the pancreas. Some reports have pointed out that the pancreas can change position in some patients, particularly women. However, few reports in the English literature have described a wandering pancreatic mass. A case of wandering neuroendocrine tumor of the head of the pancreas has been reported, involving an encapsulated mass. In that case, CT showed a shift of the large mass in the pancreas from the right to the left side of the aorta. However, wandering pancreatic adenocarcinoma has not previously been reported. Malrotated pancreas or pancreatic volvulus has been reported with wandering spleen as a very rare clinical entity, but the present case demonstrated no clinical complications, such as mobile spleen or other abdominal organs. In our case, acquired pancreatic mobilization due to tissue weakening was speculated as the cause of motility. Pancreatic carcinoma should also be considered among the differential diagnoses for mobile abdominal mass.

ABSTRACTIntroduction: In recent decades, biologics have resulted in significantly improved medical management of ulcerative colitis (UC). Rates of surgery for UC are declining. However, there is still a controversial question of the relation of biologics to postoperative adverse outcomes and the most appropriate timing for operative intervention.Areas covered: In this review, we explore the updated treatment algorithm of acute severe colitis, describe postoperative outcomes in patients exposed to biologics preoperatively, and discuss the primary indications for staging surgery in chronic refractory cases, largely with prolonged medical therapy.Expert opinion: Delaying pouch construction to when patients are in better health is suggested as a safer strategy over the long term. The surgical management of UC patients in the biologic era needs to be individualized, and a case-based multidisciplinary decision is critical for improved outcomes and a reduction of morbidity and mortality.