Tacrolimus-Associated Terminal Ileitis After Kidney Transplantation, Mimicking Crohn Disease: A Case Report.

The onset of gastroduodenal ulcers is a frequent complication after transplantation, whereas cases of intestinal ulcers are sporadic and poorly described in the literature. A patient on immunosuppressive therapy with tacrolimus and mycophenolate mofetil after kidney transplant for immunoglobulin A-related glomerulonephritis developed symptoms compatible with Crohn disease 7 months after the transplant. The patient was hospitalized for abdominal pain, diarrhea, fever, and weight loss. Imaging and a colonoscopy showed signs of idiopathic inflammatory bowel disease (IBD) affecting the terminal ileum. Behcet's disease, post-transplant lymphoma, cytomegalovirus, Epstein-Barr virus, or mycobacteria infection were excluded. Mycophenolate mofetil was suspended, and steroid therapy was increased without clinical improvement. Eleven units of blood were required for severe anemia. A further colonoscopy revealed ulcerations involving the cecal fundus, ileocecal valve, and distal ileum with bowel stenosis and suspected ischemia. The patient, therefore, underwent an emergency laparoscopic ileocolic resection. The histologic examination did not reveal clear signs of IBD, ischemia, or viral infection of the ileum. The findings seemed indicative of iatrogenic damage from immunosuppressive therapy. The postoperative course was regular, and after 12 months, the patient was asymptomatic, on low-dose tacrolimus and prednisone therapy. During immunosuppressive therapy, the onset of isolated ileal ulcers, which can mimic IBD, may be a sporadic complication.

Effectiveness and tolerance of electrochemotherapy as palliative therapy for patients with head and neck cancer and malignant melanoma and its relation to early skin reaction.

OBJECTIVES: To evaluate the efficacy and tolerance after the electrochemotherapy treatment for local therapy of cutaneous and subcutaneous metastases of head-and-neck tumors and malignant melanoma refractory to standard therapies, mainly in neck metastasis of squamous cell carcinoma. And, to evaluate the relation of this response according to the skin reaction (healing with ulcer or dry crust). METHODS: prospective pase II, observational clinical study of 56 patients with metastases of head-and-neck squamous cell carcinoma (n=13), papillary thyroid carcinoma (n=4), adenoid cystic carcinoma of parotid gland (n=1) or malignant melanoma (n=37, 5 in head). Patients were treated by electrochemotherapy (application of electrical pulses into the tumor) after the administration of a single intravenous dose of bleomycin. Kaplan-Meier curves were performed. The statistical significance was evaluated using log-rank test; p-value of less than 0.05 was considered as significant. RESULTS: Overall clinical response was observed in 47 patients (84%). Local side effects were mild in all the patients. Ten patients (76.9%) with neck metastasis of squamous cell carcinoma had some degree of response, but only in one was complete. Patients even with only partial response had a higher overall survival than patients without response (p= 0.02). Most of the patients with squamous cell carcinoma had diminution of pain and anxiety. Response rate and overall survival was higher in MM patients (86.5%) than in squamous cell cancer patients (76.9%) (p= 0.043). The healing process (dry crust/ulcer) was not associated with the overall survival (p= 0.86). CONCLUSIONS: Electrochemotherapy is associated a higher overall survival and diminution of pain and anxiety. Therefore, it is an option as palliative treatment for patients with neck metastasis of squamous cell carcinoma refractory to other therapies or even as a concomitant treatment with newer immunotherapies. The type of healing of the surgical wound could not be associated with a higher rate of response or survival. LEVEL OF EVIDENCE: III.

Drug-induced entero-colitis due to interleukin-17 inhibitor use; capsule endoscopic findings and pathological characteristics: A case report.

BACKGROUND: Interleukin-17 (IL-17) inhibitors are known to cause exacerbation or new onset of inflammatory bowel disease upon administration. However, few reports have described characteristic endoscopic and histopathologic findings, and no small intestinal lesions have been reported so far. CASE SUMMARY: A woman in her 60s with psoriasis was administered ixekizumab (IXE), an anti-IL-17A antibody, for the treatment of psoriasis. Twenty months after commencing treatment, the patient visited our hospital because of persistent diarrhea. Blood tests performed at the time of the visit revealed severe inflammation, and colonoscopy revealed multiple round ulcers throughout the colon. A tissue biopsy of the ulcer revealed infiltration of inflammatory cells and granuloma-like findings in the submucosal layer. Capsule endoscopy revealed multiple jejunal erosions. After the withdrawal of IXE, the symptoms gradually improved, and ulcer reduction and scarring of the colon were endoscopically confirmed. CONCLUSION: To the best of our knowledge, 17 reports have documented IL-17 inhibitor-induced entero-colitis with endoscopic images, endoscopic findings, and pathological characteristics, including the present case. Nine of these cases showed diffuse loss of vascular pattern, coarse mucosa/ulcer formation in the left colon, and endoscopic findings similar to those of ulcerative colitis. In the remaining eight cases, discontinuous erosions and ulcerations from the terminal ileum to the rectum were seen, with endoscopic findings similar to those of Crohn's disease. In this case, the findings were confirmed by capsule endoscopy, which has not been previously reported.

Methotrexate-associated lymphoproliferative disorder presenting as an ulcer with tendon exposure on the dorsum of the hand: a case report and literature review.

INTRODUCTION: MTX-LPD is a complication that occurs during MTX treatment. Skin lesions in MTX-LPD are often subcutaneous nodules with occasional necrosis and ulceration. Although MTX-LPD regression is frequently observed upon discontinuation of oral MTX treatment, delayed diagnosis of MTX-LPD with associated ulceration may lead to ulcer enlargement and the need for surgical procedures such as skin grafts. CASE REPORT: A 74-year-old female was diagnosed with RA and administered MTX for 3 years and 8 months. The patient presented with a 2-month-old ulcer on the dorsum of the hand. The ulcer size was 6.5 cm × 5 cm, and it was surrounded by an embankment tumor measuring 7 cm × 6 cm. Although a definitive diagnosis could not be made based on the biopsy specimen, excision of the ulcer-containing mass confirmed MTX-LPD diagnosis. MTX was discontinued, and free-flap reconstruction was performed 3 weeks after the first surgery. The postoperative period was uneventful, and MTX-LPD recurrence was not observed 10 months after the second surgery. CONCLUSION: Although MTX-LPD with ulceration is rare, it should be considered in cases of refractory ulcers in patients with RA. The discontinuation of MTX based on early MTX-LPD diagnosis is critical to avoid surgical procedures such as skin grafts and flap reconstruction.

Tocilizumab-induced mucosal injury in the terminal ileum mimicking intestinal Behçet's disease: A case report.

RATIONALE: Tocilizumab, a humanized anti-interleukin-6 (IL-6) receptor monoclonal antibody, is used for the treatment of adult-onset Still disease (AOSD). Despite its efficacy in many clinical situations, concerns have been raised regarding intestinal mucosal injury in patients receiving tocilizumab. PATIENT CONCERNS: A 64-year-old woman with a history of AOSD was admitted to our hospital with hematochezia. She had AOSD for 15 years and underwent treatment with biweekly tocilizumab 9 months prior to admission. Colonoscopy revealed a large punched-out ulcer in the terminal ileum. On pathological evaluation, nonspecific enteritis with lymphocytes and eosinophils were seen. Based on the location and shape of the lesion, we suspected intestinal Behçet's disease. However, the ulcer reduced in size over time by discontinuation of tocilizumab without additional drug treatment, indicating that it was a drug-induced ulcer. DIAGNOSIS: The patient was diagnosed with tocilizumab-induced small intestinal ulcer. INTERVENTIONS: The patient treated with the discontinuation of tocilizumab. OUTCOMES: The discontinuation of tocilizumab resulted in ulcer scarring. There was no recurrence of hematochezia. LESSONS: Tocilizumab can cause deep ulcerative lesions in the terminal ileum, which may resemble intestinal Behçet's disease. It is important to continuously monitor abdominal symptoms during tocilizumab therapy and aggressively perform colonoscopy when hematochezia or abdominal pain is observed.

Stress Ulcer Prophylaxis in Cardiac Surgery: A Retrospective Cohort Study to Analyze the Effects of SUP Cessation.

INTRODUCTION: Upper gastrointestinal bleeding (UGIB) is an important complication among critically ill adults, especially those having cardiac surgery as management is complicated by the requirement for antiplatelet/anticoagulant therapy. As a result, stress ulcer prophylaxis (SUP) has become routine practice in many centers, utilizing either proton pump inhibitors (PPIs) or histamine-2 receptor blockers (H2RBs). Recent evidence from the PEPTIC trial indicated an increase in mortality risk among cardiac surgery patients receiving PPIs compared to H2RBs. Considering these findings, alongside practical difficulties surrounding the transition to H2RBs as a prophylactic agent in New Zealand, Wellington Hospital intensive care unit elected to discontinue routine PPI use for SUP in cardiac surgery patients. A retrospective study was conducted to assess patient outcomes following the discontinuation of routine SUP. METHOD: A retrospective cohort study was conducted of all adult patients who underwent cardiac surgery at Wellington Hospital between February/2018 and January/2022, and divided patients into cohorts before and after the discontinuation of routine use of SUP on the 31st of January 2020. The primary outcomes were the rate of UGIB, oesophagogastroduodenoscopy (OGD) and 180-day postoperative mortality. Secondary outcomes included rates of postoperative Clostridium difficile enteritis, pneumonia, deep sternal wound infection, and length of stay of the index admission. RESULTS: The rate of UGIB statistically significantly increased since the cessation of routine SUP in January 2020 (2.4% vs 5.4%, P-value = .004). This finding was mirrored with the increased rates of OGD (1.9% vs 4.0%, P-value = .005). There were no significant changes in 180-day mortality, hospital length of stay, or any of the postoperative infective complications analyzed, pneumonia, deep sternal wound infection, or C difficile enteritis. CONCLUSION: This study suggests an association between routine use of SUP and reduced rates of clinically significant UGIB and OGD requirements in cardiac surgery patients without increasing risk of infective complications or postoperative mortality.

Overuse of Intravenous Proton Pump Inhibitors in General Medicine and Surgery Wards.

BACKGROUND: Overuse of stress ulcer prophylaxis is prevalent globally despite guidelines leading to the added cost, especially the intravenous proton pump inhibitor (IVPPI). This study aims to analyze the prevalence of such overuse and be aware of rational use which may help develop local guidelines. METHODS: This study analyzed the prospectively collected data on IVPPI use in adult patients in general wards of medicine and surgery at Patan Hospital, Patan Academy of Health Sciences, Nepal, from April-Jun 2022. Ethical approval was obtained. Variables analyzed were the patient's age, gender, history of peptic ulcer disease, risk for stress ulcer and gastrointestinal bleeding, the status of nil per os (NPO ≥12 hours), appropriate use of IVPPI, and cost. RESULTS: Prevalence of IVPPI use was 36.24% (274/756 admissions), surgery 39.45(189/479), medicine ward 30.68% (85/277). The mean age was 43.1 ±18.6 years, males 113(41.2%), surgery 189 (69%). Inappropriate overuse in 253(92.3%, significantly more in surgery-182 than medicine-7, p=0.001. Appropriate use was in 21 (7.7%, i.e., NPO-15, NPO + gastrointestinal bleed, and NPO + non steroid anti-inflammatory drugs each 3). CONCLUSIONS: Prevalence of IVPPI use was 36.24%. Inappropriate overuse of IVPPI was high (92.2%, 253/274), more in surgery. The nil per os status was the main reason for appropriate use of IVPPI.

Effect of phylloquinone on indomethacin-induced gastric ulceration in rats: Role of SIRT-1.

Gastric ulcer is the most common gastrointestinal disorder affecting people globally. Although many drugs are available to treat ulcers, the mortality rate is relatively high, and drugs lack selectivity to treat ulcers without causing side effects. In this study, the potential therapeutic effects of phylloquinone were tested against indomethacin-induced gastric ulcer in rats by giving rats a single oral dose of indomethacin (48 mg/kg), followed by phylloquinone (10 mg/kg) orally, once daily for six consecutive days. Phylloquinone significantly attenuated indomethacin-induced oxidative and inflammatory responses through hindering the inflammatory cascade by decreasing the levels of TNF-α, NF-κB, INOS and COX-2 which counteracts indomethacin effects. Also, it increased NAD+ which enhanced SIRT-1 level. Furthermore, phylloquinone was effective in increasing mucus secretion, decreasing acid secretion, reversing histological effects caused by indomethacin and minimizing ulcer and lesion indices All these findings indicate that phylloquinone may be used in protection and treatment of indomethacin-induced gastric ulcer.

A case of multiple hepatocellular carcinoma experiencing complete responses to sorafenib and atezolizumab-bevacizumab and developing severe, refractory venous congestive cutaneous ulcers on either regimen.

A man in his eighties presented with a history of bilateral leg congestive phlebitis, and multiple hepatocellular carcinoma (HCC) treated with sorafenib. When the dose was increased to 400 mg, ulcers appeared under both knees, which worsened, and the drug was discontinued 2 months after administration. However, the ulcers to 30 mm in diameter, requiring debridement and antibiotics. The HCC showed a complete response (CR) based on modified-RECIST criteria; however, after several rounds of locoregional therapy for recurrence, multiple HCCs and metastatic lesions in the Morrison's fossa were detected. Therefore, atezolizumab 1200 mg-bevacizumab 900 mg was started. After the first course, the patient complained of pain below both knees, and when the second course was administered, leg ulcers re-appeared and rapidly worsened. The ulcers were circular and multiple and progressed to deep digging, leading to tendon exposure. Bevacizumab-induced congestive venous ulcer was diagnosed, requiring skin grafts to heal. HCC then showed a CR based on m-RECIST criteria. Initially, the cause of the ulcer was thought to be immune-related adverse effects due to atezolizumab, but experience with sorafenib led us to conclude that the cause was stagnant venous ulcers due to vascular endothelial growth factor receptor inhibitor, which inhibited angiogenesis.

Factors Related to Delayed Adverse Events of Endoscopic Submucosal Dissection in the Duodenum.

INTRODUCTION: Endoscopic submucosal dissection for duodenal neoplasms (D-ESD) is considered a technically demanding procedure regarding the high risk of delayed adverse events. Data regarding optimal managements of ulcers after D-ESD are lacking. METHODS: A retrospective analysis was performed on consecutive 145 cases of D-ESD for superficial nonampullary duodenal epithelial tumors at a single referral center. Factors related to delayed adverse events and the healing process of ulcers after D-ESD were analyzed. RESULTS: Complete ulcer suture after D-ESD was performed in 128 cases (88%). Two delayed perforation occurred among cases with incomplete suture. Delayed bleeding occurred in 8 cases (6%) within 3 weeks. The ulcer closure rate at second-look endoscopy (SLE) was significantly low among cases with delayed bleeding (12.5% vs. 75%, p = 0.001). The bleeding rate before SLE was significantly high among patients who did not have complete ulcer closure after D-ESD (0.8% vs. 12%, p = 0.036). The ratio of lesions located in the second oral-Vater was significantly low among ulcers re-opened at SLE (38% vs. 14%, p = 0.044). Proton-pump inhibitors (PPIs) were administered for a median of 7 weeks (range 1-8 weeks). At 3 weeks, active ulcer stages were observed in a few cases, and healing or scarring was observed in most cases. CONCLUSIONS: Complete ulcer suture was related to decreased risk of delayed adverse events after D-ESD. From the bleeding period and healing process of D-ESD ulcers, the minimum required length of PPI may be 3 weeks after D-ESD.

Gastroprotective potential and mechanisms of action of Hedera nepalensis

Abstract Hedera nepalensis (H. nepalensis) , belonging to the family Araliaceae, is a medicinal plant traditionally used to treat stomach problems. The current study investigated the gastroprotective potential and the mechanism of action of H. nepalensis in diclofenac-and ethanol-induced ulcer models. Anti-oxidant and lipid peroxidation inhibitory prospects of H. nepalensis were checked out by free radical scavenging assay and UV spectrophotometer respectively. Effect of H. nepalensis on the pH, gastric total acidity of gastric juice and protective effects of H. nepalensis against ulcer models have been examined. Histopathological studies have been carried out. The aqueous methanol extract of H. nepalensis (100 µg/mL) showed anti-oxidant (83.55%) and lipid peroxidation inhibitory (70.88%) potential at 1000 µg/mL; the extract had no buffer potential. The extract (400 mg/kg) significantly (81.12% and 63.46%) showed gastroprotective effect in diclofenac and ethanol-induced rat ulcer models respectively. Histopathological studies confirmed the biochemical findings. FTIR analysis showed the presence of carboxylic acid, alkanes, conjugated alkanes, aldehydes and alkyl-aryl ethers. Gallic acid, M-coumaric acid and quercetin were found by HPLC analysis. H. nepalensis exhibited significant protection against diclofenac and ethanol induced gastric damage by anti-oxidant and lipid peroxidation suppression effects suggesting potential broad utility in treatment of diseases characterized with gastric damage.

Predictors for inappropriate proton pump inhibitor use: observational study in primary care.

BACKGROUND: Proton pump inhibitor (PPI) indications are limited to gastrointestinal disorders and ulcer prophylaxis. However, PPIs are among the most frequently prescribed drugs. AIM: To evaluate the appropriateness of PPI prescriptions and identify predictive factors for inappropriate PPI use. DESIGN AND SETTING: Observational study using a Dutch primary care database with all new PPI prescriptions between 2016 and 2018. METHOD: Individual patient data and details on PPI use were collected. The appropriateness of initiation and continuation of PPI prescriptions was evaluated using the applicable guidelines. RESULTS: In total, 148 926 patients (aged ≥18 years) from 27 general practices were evaluated. A total of 23 601 (16%) patients started PPI therapy (mean age 57 [SD 17] years, 59% female). Valid PPI indications at initiation were seen in 10 466 PPI users (44%). Predictors for inappropriately initiated PPI use were older age (odds ratio [OR] 1.03, 95% confidence interval [CI] = 1.03 to 1.03), and use of non-selective non-steroidal anti-inflammatory drugs (OR 5.15, 95% CI = 4.70 to 5.65), adenosine diphosphate receptor inhibitors (OR 5.07, 95% CI = 3.46 to 7.41), COX-2 inhibitors (also known as coxibs) (OR 3.93, 95% CI = 2.92 to 5.28), and low-dose aspirin (OR 3.83, 95% CI = 3.07 to 4.77). Despite an initial valid indication, PPI use was inaccurately continued in 32% of patients on short-course therapy for dyspepsia and in 11% of patients on ulcer prophylaxis. CONCLUSION: More than half of PPI users in primary care were found to have an inappropriate indication, with unnecessary ulcer prophylaxis related to drug use being one of the leading causes. Future initiatives to reduce PPI use for unnecessary ulcer prophylaxis and timely deprescription if PPI is no longer indicated, are needed.

Cutaneous Ulcer Caused by Apixaban Treatment Is Resolved after Replacement with Dabigatran.

Nowadays, novel oral anticoagulants (NOACs) have shown improved safety profile and efficacy compared to vitamin K antagonists in the prevention of thromboembolic events occurring during different pathological conditions. However, there are concerns and safety issues, mostly related to adverse events following interactions with other drugs, in real-world practice. We report the case of an 83-year-old woman who developed a non-bleeding leg ulcer not caused by trauma or other evident pathological conditions after 10 days of treatment with apixaban 5 mg/q.d. She was switched from apixaban to dabigatran and the leg ulcer rapidly improved and completely cicatrized in 40 days. The resolution of the ulcer and the toleration of dabigatran therapy suggest an apixaban-specific reaction; however, the pathological mechanism of ulcer onset is currently unclear. Careful evaluation of hospital databases of Molise region (Southern Italy) hospitals identified two similar cases between 2019 and 2021. These cases underline the necessity of careful post-marketing surveillance, considering the rapidly increasing number of patients treated with NOACs and patient's risk factors such as old age, high polypharmacy rate, co-morbidities, and peculiar genetic background related to NOACs pharmacokinetic features.

Comparative Effectiveness of Biologics for Endoscopic Healing of the Ileum and Colon in Crohn's Disease.

INTRODUCTION: We compared the efficacy of adalimumab, infliximab, ustekinumab, and vedolizumab on the ability to achieve endoscopic healing (EH) after 1 year of therapy in moderate-severe Crohn's disease (CD). METHODS: This was a pooled analysis of patient-level data from 299 patients with CD from 4 clinical trials. Proportions of patients treated with each biologic were compared for achieving 1-year complete EH (Simple Endoscopic Score for CD [SES-CD] <3) and ileal and colonic EH separately (SES-CD = 0). Multivariate logistic regression was used to model the relationship between biologics and 1-year outcomes and adjusted for disease duration, concomitant corticosteroid use, and prior antitumor necrosis factor failure. RESULTS: Compared with vedolizumab (4/56 [7.1%]), adalimumab (17/61 [27.9%], adjusted odds ratio [OR]: 5.79, 95% confidence interval [CI]: 1.77-18.95, P = 0.004) and infliximab (39/141 [27.7%], aOR: 4.59, 95% CI: 1.48-14.22, P = 0.008) had superior rates of 1-year EH. No significant difference was observed between vedolizumab and ustekinumab. Similar results were observed among biologic-naive patients. Among patients with baseline ileal SES-CD ≥3, no significant differences were observed between biologics for 1-year ileal EH. However, for large (>0.5 cm) ileal ulcers, infliximab (20/49 [40.8%]) had superior rates of no ileal ulcers compared with vedolizumab (2/23 [8.7%], aOR: 5.39, 95% CI: 1.03-28.05, P = 0.045). No other differences were observed. For colonic disease, compared with ustekinumab (9/31 [29.0%]), adalimumab (30/48 [62.5%], aOR: 3.97, 95% CI: 1.45-10.90, P = 0.007) had superior rates of 1-year EH in the colon, with similar trends observed for infliximab (55/105 [52.4%], aOR: 2.08, 95% CI: 0.82-5.27, P = 0.121). No other differences were observed. DISCUSSION: In this post hoc analysis, TNF-α antagonists were overall superior to vedolizumab and ustekinumab for achieving 1-year EH in moderate-severe CD patients.

Chemotherapy extravasation injuries beyond the immediate stage: A series of 15 cases treated according to a preset surgical algorithm based on time of presentation.

Chemotherapy extravasation can cause severe harm. There is a lack of evidence-based standardization on the surgical management of such injuries beyond the immediate stage. In an algorithm connecting presentation time post-injury with surgical treatment could help standardize future treatment. This study prospectively validated a preset standardized surgical algorithm based on presentation time in a consecutive series between October 2017 and October 2020. Chemotherapeutic agent, site and extent of injury, type of surgery and outcome at a minimum of 6 months' follow-up were collected. Seven thousand six hundred twelve individuals received chemotherapy during that period; 15 patients suffered extravasation injuries, 2 of whom were referred from outside our hospital. This algorithm distinguished: A) beyond the immediate stage and up to 2 days, treated with saline subcutaneous washout (SCWO) and vacuum-assisted closure (VAC) dressing; B) 2 to 5 days, open surgical decompression and VAC dressing; C) 5 to 10 days, non-operative management with surveillance; and D) more than 10 days, radical necrotic excision with or without VAC dressing and tissue reconstruction. In 2 patients in Group A and 3 patients in Group B, all vesicant symptoms resolved. Five of the 6 patients in Group C (3 vesicant, 3 non-vesicant) did not progress into necrosis or infection, and 1 case of vesicant extravasation progressed to a localized ulcer beyond this period and, as surgery was refused, led to a chronic ulcer with stiffness; 2 cases of non-vesicant extravasation developed a recall phenomenon but resolved after the third cycle. Of the 4 patients in Group D, all vesicant, 2 were treated with no complications, 1 had complex regional pain syndrome (CRPS) due to late presentation, and 1, referred with necrotizing fasciitis, underwent above-elbow amputation but died due to septic shock. This study demonstrated a uniform surgical approach in a series of 15 cases; larger studies are still needed to validate the efficacy of this protocol in reducing morbidity. LEVEL OF EVIDENCE: IV.

Ulcers on the bilateral palate mucosa following mRNA-based vaccination for coronavirus disease 2019 (COVID-19): A case report.

Severe acute respiratory syndrome coronavirus 2 has spread globally. Vaccination for coronavirus disease 2019 (COVID-19) is anticipated to reduce morbidity and mortality. However, the safety of vaccines against COVID-19 is a cause for concern and uncertainty, which leads to vaccine hesitancy. There have been some self-reported questionnaire studies regarding adverse effects after COVID-19 vaccination; however, adverse effects on the oral region are rare. In this report, we present one case of ulcers arising on the bilateral palate mucosa following COVID-19 vaccination, which was suspected to be an adverse effect of vaccination.

Ectopically Localized Epithelial Cell Clumps in Ulcers Are Derived from Reserved Crypt Stem Cells in a Mouse Model of Ulcerative Colitis.

BACKGROUND: We previously reported that clumps of a few epithelial cells were scattered in ulcer regions in a dextran sulfate sodium (DSS)-induced mouse model of ulcerative colitis (UC). AIMS: To determine the ectopically localized epithelial clumps might be derived from stem cells or their daughter progenitor cells. METHODS: Female BALB/c mice were administered DSS in drinking water for 6 days, followed by withdrawal of DSS for 6 days. Histological and immunohistochemical examinations were conducted in the distal region and proximal region of the colorectum to determine expression of stem cell markers in the epithelial clumps. RESULTS: Similar to the characteristics of UC, the ulcers were more severe in the distal region close to the anus than in the proximal region of the colorectum. Quantitative analyses revealed that the epithelial clumps appeared in relation to the severity of the ulcer, and they expressed the cell adhesion molecules E-cadherin and ß-catenin. Among stem cell markers, the epithelial clumps primarily expressed +5 cell marker Dll1 as reserved intestinal stem cells, followed by +4 cell marker Bmi1 and crypt stem cell marker Lgr5 in that order. Nuclear expression of Sox9, but not nuclear ß-catenin, was identified in the clumps. CONCLUSION: The present results suggest that most epithelial clumps comprised crypt-derived, reserved stem cells, which might have potential for mucosal healing.

Severe oral ulcerative and lichenoid lesions associated with adrenal insufficiency in a patient treated with nivolumab: Report of a case and review of literature.

Nivolumab, an antibody against anti-programmed death type 1, has been used for treatment of advanced non-small cell lung cancer with improvement of overall survival. Usually, diarrhea, cutaneous rash, and pruritus are reported as the most common immune-related adverse effects of nivolumab therapy. Oral lesions and secondary adrenal insufficiency sometimes occur but usually are rare events. We report a case of a patient treated with nivolumab who then showed persistent oral ulcerative and lichenoid lesions, which were refractory to topical corticosteroids. The oral lesions were concomitant to nivolumab-induced adrenal insufficiency. These adverse events led to nivolumab discontinuation, which favored oral lesion healing and adrenal insufficiency remission. Through a brief review of the literature concerning nivolumab toxicity in the oral cavity, we discuss the clinical aspect and management of these lesions.

[Patient with Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma with Small Intestinal Perforation Development during Chemotherapy].

Monomorphic epitheliotropic intestinal T-cell lymphoma(MEITL)is classified under type Ⅱ enteropathy-associated T-cell lymphoma(EATL). It is a rare disease with a low incidence rate. This study reports a case of a patient with MEITL who developed small intestinal perforation during chemotherapy. The patient was a 55-year-old woman who presented to a previous clinic with epigastric pain. Enteroscopy results showed a map-like ulcer in the jejunum. Examination of the tissue specimen collected from this site suggested T-cell lymphoma. The patient was referred to our hospital for chemotherapy. Seven days following the initiation of chemotherapy, an abdominal computed tomography(CT)revealed free air, leading to a diagnosis of gastrointestinal perforation. Emergency surgery was performed. Intraoperatively, bowel perforation and a degenerative ulcer were observed at 95 cm and 80 to 115 cm from the Treitz' ligament, respectively. In addition, all-layer intestinal necrosis was noted 150 and 90 cm from the terminal ileum. Total resection and anastomosis were performed. Postoperatively, the patient developed sepsis due to chemotherapy-related pancytopenia but recovered. She was discharged on postoperative day 24. Subsequently, positron emission tomography(PET)-CT revealed residual intestinal tumor cells and peritoneal dissemination. Chemotherapy was initiated, but there was no response. The patient died after 6.5 months. A radical treatment for MEITL has not yet been established. More case reports are needed to improve the prognosis of this disease.