A case report of typhlitis during novel use of ropidoxuridine-capecitabine-radiotherapy for treatment-naïve rectal cancer.

BACKGROUND: Rectal carcinomas are tumors that arise from the last 12 cm of the large intestine closest to the anus. They generally have a modest prognosis exacerbated by a high local recurrence rate if radiosensitizing chemotherapy is not given during radiotherapy. This case report discusses the clinical trial treatment of a patient with rectal adenocarcinoma by a new ropidoxuridine-capecitabine-radiotherapy combination. This case report is novel due to the patient's participation in an accelerated titration phase I clinical trial and the resultant rare adverse event of treatment-related sigmoid typhlitis. CASE PRESENTATION: The patient was an 82-year-old female who noticed hematochezia and change in stool caliber over a period of 3 months. A rectal mass was identified by biopsy as a microsatellite stable adenocarcinoma. A planned total neoadjuvant treatment involved eight cycles of leucovorin calcium (folinic acid)-fluorouracil-oxaliplatin (mFOLFOX6) chemotherapy, followed by a clinical trial combination of ropidoxuridine-capecitabine-radiotherapy, prior to definitive surgery. The patient began daily intensity modulated pelvic radiotherapy with concurrent twice-daily oral ropidoxuridine and twice-daily oral capecitabine to be given over 6 weeks. After 14 days of ropidoxuridine-capecitabine-radiotherapy, the patient developed sigmoid typhlitis requiring a 10-day hospitalization and 14-day disruption of treatment. The patient died 27 days after the start of ropidoxuridine-capecitabine-radiotherapy. This adverse event was listed as a definite attribution to the ropidoxuridine-capecitabine treatment; pharmacokinetic and pharmacodynamic data showed low ropidoxuridine metabolite DNA incorporation and high capecitabine metabolite concentration. The accelerated titration phase I clinical trial has been subsequently closed to accrual (NCT04406857). CONCLUSIONS: We believe this case report demonstrates the decision-making process for terminating a phase I accelerated titration designed clinical trial. The report also presents the rare complication of sigmoid typhlitis as a treatment-attributed adverse event. In this case, a ropidoxuridine-capecitabine combination was used as an investigational radiosensitizing treatment now with a narrower future clinical development pathway.

Sonographic and Clinical Features of Typhlitis in Pediatric Cancer Patients on Chemotheaphy at Tikur Anbessa Specialized Hospital, Ethiopia, 2021.

Background: Typhlitis, (neutropenic enterocolitis), is a necrotizing enteropathy of the right colon, and is characterized by the clinical triad of fever, abdominal pain, neutropenia and imaging findings of right-side colonic inflammation. It is seen in the setting of severe neutropenia in immune suppressed patients who undergo treatment for malignancies, in those who have organ transplant(s) or congenital or other acquired immunosuppression. We report the clinical and imaging findings of typhlitis in pediatric cancer patients who had received chemotherapy in the largest tertiary center in Addis Ababa, Ethiopia over a period of 20 months. Methods: The medical records of hospitalized cancer patients on treatment and with suspected typhlitis and with ultrasound reports were screened (November 2018- July 2020). Retrospective analysis of the clinical and sonographic data of those with typhlitis was done. Results: Typhlitis was identified in 4.2% (12/286) of the patients on chemotherapy. 11 (91.7%) had hematologic malignancies (leukemia, lymphoma), one had a solid tumor (Head and neck embryonal RMS). Most (83.3%) had abdominal pain, diarrhea and neutropenia. Fever was identified in 67.7%. All had ultrasound evidence of typhlitis. and treated with IV antibiotics. Neither complications requiring surgical intervention nor death were seen. Conclusion: The magnitude of disease was comparable to what had previously been reported in other studies. While the presence of clinical a triad should prompt suspicion for the diagnosis, sonography can be used for confirmation and follow up obviating radiation, with good access in a resource limited setting.

Automated Ascertainment of Typhlitis From the Electronic Health Record.

PURPOSE: Adverse events (AEs) on Children's Oncology Group (COG) trials are manually ascertained using Common Terminology Criteria for Adverse Events. Despite significant effort, we previously demonstrated that COG typhlitis reporting sensitivity was only 37% when compared with gold standard physician chart abstraction. This study tested an automated typhlitis identification algorithm using electronic health record data. METHODS: Electronic health record data from children with leukemia age 0-22 years treated at a single institution from 2006 to 2019 were included. Patients were divided into derivation and validation cohorts. Rigorous chart abstraction of validation cohort patients established a gold standard AE data set. We created an automated algorithm to identify typhlitis matching Common Terminology Criteria for Adverse Events v5 that included antibiotics, neutropenia, and non-negated mention of typhlitis in a note. We iteratively refined the algorithm using the derivation cohort and then applied the algorithm to the validation cohort; performance was compared with the gold standard. For patients on trial AAML1031, COG AE report performance was compared with the gold standard. RESULTS: The derivation cohort included 337 patients. The validation cohort included 270 patients (961 courses). Chart abstraction identified 16 courses with typhlitis. The algorithm identified 37 courses with typhlitis; 13 were true positives (sensitivity 81.3%, positive predictive value 35.1%). For patients on AAML1031, chart abstraction identified nine courses with typhlitis, and COG reporting correctly identified 4 (sensitivity 44.4%, positive predictive value 100.0%). CONCLUSION: The automated algorithm identified true cases of typhlitis with higher sensitivity than COG reporting. The algorithm identified false positives but reduced the number of courses needing manual review by 96% (961 to 37) by detecting potential typhlitis. This algorithm could provide a useful screening tool to reduce manual effort required for typhlitis AE reporting.

Supportive care in pediatric acute myeloid leukemia:Expert-based recommendations of the NOPHO-DB-SHIP consortium.

INTRODUCTION: Pediatric acute myeloid leukemia (AML) is the second most common type of pediatric leukemia. Patients with AML are at high risk for several complications such as infections, typhlitis, and acute and long-term cardiotoxicity. Despite this knowledge, there are no definite supportive care guidelines as to what the best approach is to manage or prevent these complications. AREA COVERED: The NOPHO-DB-SHIP (Nordic-Dutch-Belgian-Spain-Hong-Kong-Israel-Portugal) consortium, in preparation for a new trial in pediatric AML patients, had dedicated meetings for supportive care. In this review, the authors discuss the available data and outline recommendations for the management of children and adolescents with AML with an emphasis on hyperleukocytosis, tumor lysis syndrome, coagulation abnormalities and bleeding, infection, typhlitis, malnutrition, cardiotoxicity, and fertility preservation. EXPERT OPINION: Improved supportive care has significantly contributed to increased cure rates. Recommendations on supportive care are an essential part of treatment for this highly susceptible population and will further improve their outcome.

Investigation of typhlitis in bone marrow transplant patients in a stem cell transplant unit.

Typhlitis is a special type of enterocolitis that specifically develops in immunosuppressive patients with hematological malignancies. Typhlitis is a common consideration after bone marrow transplantation due to high-dose chemotherapy that is used in conditioning regimens those contain high-dose cytotoxic chemotherapeutic agents. Although there are several studies about typhlitis during chemotherapy or in leukemia patients, there is not enough data evaluating its relationship between stem cell transplant in adults. Therefore, the current study aimed to analyze the possible causes that may lead to the development of typhlitis in hematopoietic stem cell recipient patients. This retrospective study included 210 adult patients who underwent bone marrow transplantation between January 2017 and December 2019. Pediatric patients (patients younger than 18 years of age) were excluded. Patients' data were evaluated to determine their effects on typhlitis and the mortality risk of the patients with typhlitis. The analysis of the variables was performed using the IBM SPSS Statistics for Windows version 26 (IBM Corp., Armonk, NY).Variables were analyzed at a 95% confidence level and a P value <0.05 was considered significant. Typhlitis developed in 23 (10.9%) transplant patients. Male sex, length of hospital stay, presence of febrile neutropenia, antibiotic and antifungal use, need for switching antibiotics, duration of neutropenia, diarrhea and antibiotic use in days were risk factors for development of typhlitis. It was observed that 100-days mortality was higher in typhlitis group reaching to a statistical significance (P < .05). In multiple logistic regression analysis, presence of mucositis and additional source of infection were determined as independent risk factors for the development of typhlitis in bone marrow transplant patients. This study provides valuable information for bone marrow transplant patients through an analysis of risk factors for the development of typhlitis. According to our results, mucositis and additional bacterial infections were found as risk factors for typhlitis therefore it would be beneficial for clinicians to consider these factors in patient follow-up. However, due to the retrospective nature of our study, prospective studies are needed to investigate risk factors and optimum treatment methods for typhlitis.

Heterakis isolonche Infection Associated with Severe Nodular Typhlitis and Suspect Aberrant Pulmonary Migration in a Golden Pheasant (Chrysolopus pictus).

This case report describes the clinical, parasitologic, pathologic, and histologic characteristics of a golden pheasant (Chrysolopus pictus) with an infection of Heterakis isolonche in Mississippi. An approximately 2-yr-old golden pheasant from a flock of 8 to 10 birds was submitted to the Poultry Research and Diagnostic Laboratory in Pearl, MS, for necropsy. Clinical history indicated that three flock mates had died of unknown causes in the past. At necropsy, the submitted pheasant showed severe nodular typhlitis associated with the presence of numerous whitish small nematodes inside the cecal walls and lumen with morphologic features consistent with H. isolonche. The histologic examination showed multifocal to coalescing, nodular, granulomatous, and lymphocytic typhlitis with fibroplasia, and multiple intralesional nematodes. Furthermore, the presence of similar nematodes in the lung indicated a possible aberrant migration of Heterakis sp. to this organ. The flock was subsequently treated with an oxfendazole-containing dewormer and suffered no further losses.

Reporte de Caso- Infección por Heterakis isolonche asociada a tiflitis nodular severa y posible migración pulmonar aberrante en un faisán dorado (Chrysolopus pictus). Este informe de caso describe las características clínicas, parasitológicas, patológicas e histológicas de un faisán dorado (Chrysolopus pictus) con una infección por Heterakis isolonche en Mississippi. Un faisán dorado de aproximadamente dos años de edad de una parvada de ocho a diez aves fue remitido al Laboratorio de Investigación y Diagnóstico Avícolas en Pearl, Mississippi, para su necropsia. La historia clínica indicó que tres aves de la misma parvada habían muerto previamente por causas desconocidas. En la necropsia se observó tiflitis nodular grave asociada con la presencia de numerosos nematodos pequeños blanquecinos dentro de las paredes cecales y en el lumen con características morfológicas compatibles con H. isolonche. El examen histológico mostró tiflitis multifocal nodular coalescente, granulomatosa y linfocítica con fibroplasia y múltiples nematodos intralesionales. Además, la presencia de nematodos similares en el pulmón indicó una posible migración aberrante de Heterakis sp. a este órgano. Posteriormente, la parvada fue tratada con un antiparasitario que contenía oxfendazol y no presentó más pérdidas por mortalidad.

The involvement of the primo vascular system in local enteritis and its modification by electroacupuncture.

Introduction: The primo vascular system (PVS), an intensive network structure, has been claimed to be representative of the acupuncture meridian. Here, we explored the role of the PVS in local enteritis and its modification by acupuncture. Methods: Chronic cecitis in rabbits was induced by 2,4,6-trinitro-benzene-sulfonic acid (TNBS). The PVS on the cecum was visualized with trypan blue staining, and collected with the help of microsurgical forceps under an optical stereomicroscope. Results: The increased primo vessels (PVs) and primo nodes (PNs) of the PVS on the surface of the cecum were induced by local inflammation, which was positively correlated with the inflammatory cells in the cecal mucosa. Tandem mass tag (TMT) based proteomic analysis revealed that 110 differentiated proteins of the PVS existed between TNBS-treated and control rabbits; 65 proteins were upregulated, while 45 proteins were downregulated. These proteins were mainly enriched in inflammation- and immunity-related processes, such as inflammatory cell proliferation, antigen presentation, and cell adhesion in the proliferated PVS (data are available via ProteomeXchange with the identifiers PXD034280). Importantly, TNBS-induced cecitis, the proliferated PVS and inflammation response-related proteins (CD40, CD45, HLA-DRA1, LAMP1, JAGN1 and FGL1) in the PVS were alleviated or reversed by repetitive electroacupuncture (EA) stimulations. Conclusion: These results suggest that the proliferated PVS and its active inclusions were related to the inflammatory process, which was modified by EA. Our study provides a new avenue for further exploration of the mechanism by which EA exerts anti-inflammatory effects.

Neutropenic Enterocolitis: Case report and literature review.

Typhlitis, is also known as neutropenic enterocolitis, affects the cecum and distal ileum. It was frequently encountered in pediatric patients who were undergoing treatment for leukemia. Nonetheless, it can affect adult patients, regardless of the cause of the immunosuppression. We report the case of a 20-year-old patient who was receiving chemotherapy for Osteosarcoma, who had a 6-day history of nausea and vomiting, fever sensation, diarrhea, and diffuse abdominal pain. Physical examination was relevant for hemodynamic instability, a distended and tender abdomen predominantly in the right iliac fossa. The laboratory workup showed severe neutropenia, thrombocytopenia, and electrolyte disturbances. The image studies evidenced edema of the ascending colon and cecum. Treatment was started with vasopressor support, correction of electrolyte alterations, blood cell and platelet transfusion, G-CSF, hydration, broad spectrum antibiotic therapy, initially with adequate clinical and laboratory response. After a few days, he presented lower gastrointestinal bleeding which was treated by conservative management. In conclusion, typhlitis must be suspected in every patient developing neutropenia as a reaction to chemotherapy and who also presents gastrointestinal symptoms, such as nausea, vomiting, diarrhea, and intense abdominal pain.

Typhlitis induced by Histomonas meleagridis affects relative but not the absolute Escherichia coli counts and invasion in the gut in turkeys.

Unlike in chickens, dynamics of the gut microbiome in turkeys is limitedly understood and no data were yet published in context of pathological changes following experimental infection. Thus, the impact of Histomonas meleagridis-associated inflammatory changes in the caecal microbiome, especially the Escherichia coli population and their caecal wall invasion in turkeys was investigated. Birds experimentally inoculated with attenuated and/or virulent H. meleagridis and non-inoculated negative controls were divided based on the severity of macroscopic caecal lesions. The high throughput amplicon sequencing of 16SrRNA showed that the species richness and diversity of microbial community significantly decreased in severely affected caeca. The relative abundances of operational taxonomic units belonging to Anaerotignum lactatifermentans, E. coli, and Faecalibacterium prausnitzii were higher and paralleled with a decreased abundances of those belonging to Alistipes putredinis, Streptococcus alactolyticus, Lactobacillus salivarius and Lactobacillus reuteri in birds with the highest lesion scores. Although the relative abundance of E. coli was higher, the absolute count was not affected by the severity of pathological lesions. Immunohistochemistry showed that E. coli was only present in the luminal content of caecum and did not penetrate even severely inflamed and necrotized caecal wall. Overall, it was demonstrated that the fundamental shift in caecal microbiota of turkeys infected with H. meleagridis was attributed to the pathology induced by the parasite, which only led to relative but not absolute changes in E. coli population. Furthermore, E. coli cells did not show tendency to penetrate the caecal tissue even when the intestinal mucosal barriers were severely compromised.

Russell Body Typhlitis: A Case Report and Literature Review.

Russell bodies are accumulation of immunoglobulin in plasma cells forming intracytoplasmic inclusions. Russell body colitis is rare with only 3 cases described in the English literature up to date. We report a 78-year-old male with cirrhosis showing prominent cecal infiltration of Russell body containing plasma cells. Plasma cells showed no nuclear atypia or mitoses, and no evidence of light chain restriction. In this article, we report a fourth case of Russell body colitis, that is unique in being localized to the cecum in contrast to the other 3, 1 of which was in an inflammatory polyp in the sigmoid colon, 1 in a rectal tubulovillous adenoma and 1 as part of diffuse gastrointestinal disease. This is therefore the first report of localized Russell body typhlitis, occurring in a cirrhotic patient in whom an adjacent erosion was likely nonsteroidal anti-inflammatory drug-associated, a combination that may have facilitated the formation of Russell bodies.

COVID-19-associated pancytopenia and typhlitis.

Neutropenic enterocolitis is also known as typhlitis, is characterized by severe inflammation in the bowel loops. It is often seen in immunosuppressed patients, and it has high morbidity and mortality. Although the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily affects the respiratory system and causes COVID-19 (Coronavirus Disease 2019), it may affect hematopoietic and gastrointestinal systems. Herein, we present a rare case of COVID-19-associated pancytopenia and typhlitis in a 60-year-old female who presented with abdominal pain. Contrast-enhanced abdominal computed tomography (CT) demonstrated the bowel wall thickening in the cecum and ascending colon compatible with enterocolitis. Moreover, the chest CT showed bilateral, peripheral, and multifocal ground-glass opacities, consistent with COVID-19 pneumonia. We also aimed to emphasize the laboratory, clinical, and CT findings of the patient.

Eimeria ninakohlyakimovae casts NOX-independent NETosis and induces enhanced IL-12, TNF-α, IL-6, CCL2 and iNOS gene transcription in caprine PMN.

Eimeria ninakohlyakimovae represents a highly pathogenic coccidian parasite causing severe haemorrhagic typhlocolitis in goat kids worldwide. NETosis was recently described as an efficient defense mechanism of polymorphonuclear neutrophils (PMN) acting against different parasites in vitro and in vivo. In vitro interactions of caprine PMN with parasitic stages of E. ninakohlyakimovae (i. e. oocysts and sporozoites) as well as soluble oocyst antigens (SOA) were analyzed at different ratios, concentrations and time spans. Extracellular DNA staining was used to illustrate classical molecules induced during caprine NETosis [i. e. histones (H3) and neutrophil elastase (NE)] via antibody-based immunofluorescence analyses. Functional inhibitor treatments with DPI and DNase I were applied to unveil role of NADPH oxidase (NOX) and characterize DNA-backbone composition of E. ninakohlyakimovae-triggered caprine NETosis. Scanning electron microscopy (SEM)- and immunofluorescence-analyses demonstrated that caprine PMN underwent NETosis upon contact with sporozoites and oocysts of E. ninakohlyakimovae, ensnaring filaments which firmly entrapped parasites. Detailed co-localization studies of E. ninakohlyakimovae-induced caprine NETosis revealed presence of PMN-derived DNA being adorned with nuclear H3 and NE corroborating molecular characteristics of NETosis. E. ninakohlyakoimovae-induced caprine NETosis was found to be NOX-independent since DPI inhibition led to a slight decrease of NETosis. Exposure of caprine PMN to vital E. ninakohlyakimovae sporozoites as well as SOA resulted in up-regulation of IL-12, TNF-α, IL-6, CCL2 and iNOS gene transcription in stimulated PMN. Since vital E. ninakohlyakimovae-sporozoites induced caprine NETosis, this effective entrapment mechanism might reduce initial sporozoite epithelial host cell invasion during goat coccidiosis ultimately resulting in less macromeront formation and reduced merozoites I production.

Obstructed ileocaecal tuberculosis with splenic tuberculosis and solid pseudopapillary tumour of tail of pancreas in an immunocompetent woman.

A 22-year-old young woman presented with fever, lower abdominal pain and vomiting for 20 days. She had persistent fever and abdominal pain. Fever panel was negative. Clinical features were suggestive of subacute small bowel obstruction. Contrast-enhanced CT abdomen showed thickening of distal ileum, ileocaecal junction and caecum with conglomerate necrotic nodal mass in the ileocolic mesentry along with a lesion in the tail of pancreas. Patient was discussed with multidisciplinary team and decided to undergo a single-stage procedure after adequate nutritional optimisation. During optimisation, she underwent acute obstruction and hence taken up for emergency laparotomy proceeded to right haemicolectomy with distal pancreatectomy and splenectomy 4 weeks after the time of admission. Histopathology showed ileocaecal tuberculosis and solid pseudopapillary tumour with margins free of tumour. Approach of obstructed ileocaecal tuberculosis in the setting of incidental diagnosis of solid pseudopapillary tumour of pancreas in a moribund patient was challenging.

Typhlitis Associated With Natural Trichuris sp. Infection in Cats.

Trichuris spp. infections can cause typhlitis or typhlocolitis in many species, but there are no published studies about its pathology in cats. Trichuris sp. infection in cats appears to be rare in most parts of the world but is frequent in some tropical and subtropical regions. The purpose of this study was to describe intestinal lesions associated with natural Trichuris sp. infections in cats of St. Kitts, West Indies. Comprehensive autopsies, histopathological assessment of small and large intestine, and total worm counts were performed in a cross-sectional study of 30 consecutive feline mortalities. Trichuris were found in 17 of 30 (57%; 95% confidence interval, 39%-74%) of the study cats with a median worm count of 11 (range, 1-170), indicating most cats had a low-intensity infection. Trichuris infection was associated with typhlitis but not consistency of feces or body condition score. In most cats examined, the typhlitis was categorized as mild (10/15, 67%) and, less frequently, moderate (2/15, 13%) or marked (3/15, 20%). The inflammatory infiltrate varied from predominantly eosinophilic (5/15, 33%) to neutrophilic (4/15, 27%), a mixture of eosinophilic and neutrophilic (2/15, 13%), a mixture of neutrophilic and lymphoplasmacytic (1/15, 7%), or a mixture of eosinophilic, neutrophilic, and lymphoplasmacytic (3/15, 20%). In some cats, surface erosions and catarrhal exudate were adjacent to adult worms. These findings are similar to those reported with low-intensity Trichuris infections in other species.

Intussusception caused by typhlitis: a rare complication in a patient with acute lymphoblastic leukemia after chemotherapy.

INTRODUCTION: Intussusception, which is common in pediatric patients but rare in adults with leukemia, usually presents with an intralumenal lesion as a lead point in adults. CASE REPORT: We herein report the case of a 38-year-old female who developed right lower quadrant abdominal pain and fever on day 16 of chemotherapy. Abdominal computed tomography showed ileocecal intussusception. The patient underwent surgery, and the definitive pathological diagnosis was typhlitis leading to intussusception. Albeit very rare in adults, typhlitis-induced intussusception should be suspected in those with leukemia presenting with abdominal pain.

Fatal parasite-induced enteritis and typhlocolitis in horses in Southern Brazil.

Diseases related to the alimentary system are the main cause of death in horses. This retrospective study aimed to describe the pathological findings of fatal parasite-induced enteritis and typhlocolitis caused by cyathostominae, Eimeria leuckarti, Balantidium coli, and Strongyloides westeri in horses. The records of parasite-induced intestinal lesions in horses necropsied in Southern Brazil between 2005 and 2017 were reviewed. Ten horses had fatal parasitic enteritis and/or typhlocolitis, and the main causes were: cyathostominae typhlocolitis (6/10), E. leuckarti enteritis (1/10), S. westeri enteritis (1/10), B. coli colitis related to cyathostominae (1/10), and infection by multiple agents (1/10). Cyathostominae typhlocolitis showed marked mucosal thickening, with multifocal elevated nodules containing tangled filiform parasites. Microscopic examination revealed that the mucosa and submucosa had encysted parasitic structures surrounded by eosinophilic and granulomatous inflammation. E. leuckarti enteritis was microscopically characterized by macrogamonts, microgamonts, and oocysts inside the host cells. S. westeri enteritis showed microscopic atrophy of the villi with numerous mucosal encysted parasitic structures. B. coli typhlocolitis showed severe diffuse mucosal reddening, with microscopic superficial mucosal necrosis associated with multiple protozoan trophozoites. Fatal parasite-induced enteritis and typhlocolitis are important causes of death in horses in Southern Brazil.

Clostridium difficile colitis: CT findings and differential diagnosis.

Clostridium difficile infection (CDI) is a severe and potentially deadly infectious colitis whose incidence is dramatically increasing in the last decades, with more virulent strains. CDI should be suspected in case of unexplained diarrhea and abdominal pain in patients with a recent history of antibiotic use and healthcare exposures; diagnosis is based on a combination of clinical and laboratory findings with demonstration of C. difficile toxins by stool test. The advantages of contrast-enhanced computed tomography (CECT) are the noninvasiveness and the ability to evaluate both the colonic wall and the adjacent soft tissues. Considerable overlap exists between the CECT findings of CDI and those of colitis of other origins, such as typhlitis, ischemic colitis, graft-versus-host disease, radiation colitis and inflammatory bowel diseases; however, some features may help distinguish between these conditions. This paper provides a comprehensive overview of the imaging features of Clostridium difficile colitis and its mimics, with a view to assist the radiologist in reaching the correct diagnosis.