{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:36:47Z","timestamp":1792085807855,"version":"4.4.0"},"reference-count":52,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,20]],"date-time":"2021-06-20T00:00:00Z","timestamp":1624147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background: Neutropenic enterocolitis (NE), which in the past was also known as typhlitis or ileocecal syndrome for the segment of the gastrointestinal tract most affected, is a nosological entity that is difficult to diagnose and whose pathogenesis is not fully known to date. Initially described in pediatric patients with leukemic diseases, it has been gradually reported in adults with hematological malignancies and non-hematological conditions, such as leukemia, lymphoma, multiple myeloma, aplastic anemia, and also myelodysplastic syndromes, as well as being associated with other immunosuppressive causes such as AIDS treatment, therapy for solid tumors, and organ transplantation. Therefore, it is associated with high mortality due to the rapid evolution in worse clinical pictures: rapid progression to ischemia, necrosis, hemorrhage, perforation, multisystem organ failure, and sepsis. Case report: A case report is included to exemplify the clinical profile of patients with NE who develop sepsis. Literature Review: To identify a specific profile of subjects affected by neutropenic enterocolitis and the entity of the clinical condition most frequently associated with septic evolution, a systematic review of the literature was conducted. The inclusion criteria were as follows: English language, full-text availability, human subjects, and adult subjects. Finally, the papers were selected after the evaluation of the title and abstract to evaluate their congruity with the subject of this manuscript. Following these procedures, 19 eligible empirical studies were included in the present review. Conclusions: Despite the recent interest and the growing number of publications targeting sepsis and intending to identify biomarkers useful for its diagnosis, prognosis, and for the understanding of its pathogenesis, and especially for multi-organ dysfunction, and despite the extensive research period of the literature review, the number of publications on the topic \u201cneutropenic enterocolitis and sepsis\u201d appears to be very small. In any case, the extrapolated data allowed us to conclude that the integration of medical history, clinical and laboratory data, radiological imaging, and macroscopic and histological investigations can allow us to identify a specific pathological profile.<\/jats:p>","DOI":"10.3390\/medicina57060638","type":"journal-article","created":{"date-parts":[[2021,6,20]],"date-time":"2021-06-20T22:00:02Z","timestamp":1624226402000},"page":"638","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Neutropenic Enterocolitis and Sepsis: Towards the Definition of a Pathologic Profile"],"prefix":"10.3390","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8179-1072","authenticated-orcid":false,"given":"Giuseppe","family":"Bertozzi","sequence":"first","affiliation":[{"name":"Section of Legal Medicine, Department of Clinical and Experimental Medicine, University of Foggia, Ospedale Colonnello D\u2019Avanzo, Viale Europa 12, 71100 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aniello","family":"Maiese","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology, Medical, Molecular and Critical Area, Institute of Legal Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Passaro","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7335-6137","authenticated-orcid":false,"given":"Alberto","family":"Tosoni","sequence":"additional","affiliation":[{"name":"CEMAD Digestive Disease Center, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3932-3803","authenticated-orcid":false,"given":"Antonio","family":"Mirijello","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania De","family":"Simone","sequence":"additional","affiliation":[{"name":"Section of Legal Medicine, Department of Clinical and Experimental Medicine, University of Foggia, Ospedale Colonnello D\u2019Avanzo, Viale Europa 12, 71100 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedetta","family":"Baldari","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Sapienza University of Rome, 00186 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6464-3249","authenticated-orcid":false,"given":"Luigi","family":"Cipolloni","sequence":"additional","affiliation":[{"name":"Section of Legal Medicine, Department of Clinical and Experimental Medicine, University of Foggia, Ospedale Colonnello D\u2019Avanzo, Viale Europa 12, 71100 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"La Russa","sequence":"additional","affiliation":[{"name":"Section of Legal Medicine, Department of Clinical and Experimental Medicine, University of Foggia, Ospedale Colonnello D\u2019Avanzo, Viale Europa 12, 71100 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1093\/cid\/cis998","article-title":"Neutropenic enterocolitis, a growing concern in the era of widespread use of aggressive chemotherapy","volume":"56","author":"Snydman","year":"2013","journal-title":"Clin. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s11938-006-0043-2","article-title":"Neutropenic enterocolitis","volume":"9","author":"Davila","year":"2006","journal-title":"Curr. Treat. Options Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1097\/MPH.0b013e3181b1ee28","article-title":"Risk factors for typhlitis in pediatric patients with cancer","volume":"31","author":"Moran","year":"2009","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1600-0609.2005.00442.x","article-title":"Neutropenic enterocolitis in adults: Systematic analysis of evidence quality","volume":"75","author":"Mey","year":"2005","journal-title":"Eur. J. Haematol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1093\/annonc\/mdl337","article-title":"Diarrhea in neutropenic patients: A prospective cohort study with emphasis on neutropenic enterocolitis","volume":"18","author":"Aksoy","year":"2007","journal-title":"Ann. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1136\/gutjnl-2011-300563","article-title":"Practice guidance on the management of acute and chronic gastrointestinal problems arising as a result of treatment for cancer","volume":"61","author":"Andreyev","year":"2012","journal-title":"Gut"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1002\/1097-0142(19900215)65:4<1041::AID-CNCR2820650433>3.0.CO;2-A","article-title":"Typhlitis. An 18-year experience and postmortem review","volume":"65","author":"Katz","year":"1990","journal-title":"Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1179\/102453310X12583347009577","article-title":"Factors associated with severe sepsis: Prospective study of 94 neutropenic febrile episodes","volume":"15","author":"Jeddi","year":"2010","journal-title":"Hematology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4062829","DOI":"10.1155\/2016\/4062829","article-title":"A Pathophysiological Insight into Sepsis and Its Correlation with Postmortem Diagnosis","volume":"2016","author":"Pomara","year":"2016","journal-title":"Mediat. Inflamm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.yjmcc.2009.12.013","article-title":"Tumor necrosis factor-\u03b1 produced in cardiomyocytes mediates a predominant myocardial inflammatory response to stretch in early volume overload","volume":"49","author":"Chen","year":"2010","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1093\/annonc\/mdf084","article-title":"Gastrointestinal toxicity associated with weekly docetaxel treatment","volume":"13","author":"Stemmler","year":"2002","journal-title":"Ann. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1007\/s00280-015-2903-8","article-title":"Antimitotic drugs in the treatment of cancer","volume":"76","author":"Visagie","year":"2015","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_13","first-page":"106","article-title":"Systemic treatment-induced gastrointestinal toxicity: Incidence, clinical presentation and management","volume":"25","author":"Boussios","year":"2012","journal-title":"Ann. Gastroenterol."},{"key":"ref_14","first-page":"59","article-title":"Clinical characteristics of colitis induced by taxane-based chemotherapy","volume":"33","author":"Chen","year":"2020","journal-title":"Ann. Gastroenterol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.ejphar.2014.07.025","article-title":"Cisplatin in cancer therapy: Molecular mechanisms of action","volume":"740","author":"Dasari","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Weber, G.F., and Weber, G.F. (2015). DNA Damaging Drugs. Molecular Therapies of Cancer, Springer International Publishing.","DOI":"10.1007\/978-3-319-13278-5_2"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.bbcan.2013.12.002","article-title":"Doxorubicin, DNA torsion, and chromatin dynamics","volume":"1845","author":"Yang","year":"2014","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_18","unstructured":"(2021, April 17). Thymidylate Synthase Inhibitor\u2014An Overview|ScienceDirect Topics n.d. Available online: https:\/\/www.sciencedirect.com\/topics\/chemistry\/thymidylate-synthase-inhibitor."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3751","DOI":"10.3748\/wjg.v20.i14.3751","article-title":"Gastro-intestinal toxicity of chemotherapeutics in colorectal cancer: The role of inflammation","volume":"20","author":"Lee","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_20","first-page":"41","article-title":"Clinical efficacy of intravenous colistin therapy in combination with ceftazidime in severe MDR P. aeruginosa systemic infections in two haematological patients","volume":"14","author":"Tascini","year":"2006","journal-title":"Le Infez. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.amjsurg.2011.02.012","article-title":"The surgical management of abdominal pain in the multiple myeloma patient","volume":"203","author":"Garrett","year":"2012","journal-title":"Am. J. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1002\/pbc.24531","article-title":"The complication of gastro-enteric fistulisation in neutropenic enterocolitis secondary to aplastic anaemia","volume":"61","author":"Teichmann","year":"2014","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Royo-Cebrecos, C., Gudiol, C., Ardanuy, C., Pomares, H., Calvo, M., and Carratal\u00e0, J. (2017). A fresh look at polymicrobial bloodstream infection in cancer patients. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0185768"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1080\/1042819031000149449","article-title":"Fatal anerobic bacteremia after hematopoietic stem cell transplant","volume":"45","author":"Slavin","year":"2004","journal-title":"Leuk. Lymphoma"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1086\/516112","article-title":"Clostridium difficile infection is a risk factor for bacteremia due to vancomycin-resistant enterococci (VRE) in VRE-colonized patients with acute leukemia","volume":"25","author":"Roghmann","year":"1997","journal-title":"Clin. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1081\/CNV-100106141","article-title":"Severe abdominal infections in neutropenic patients","volume":"19","author":"Glasmacher","year":"2001","journal-title":"Cancer Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1080\/10520295.2018.1535138","article-title":"An immunohistochemical study of the diagnostic value of TREM-1 as marker for fatal sepsis cases","volume":"94","author":"Maiese","year":"2019","journal-title":"Biotech. Histochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e13155","DOI":"10.1111\/ecc.13155","article-title":"Does a neutropenic diet reduce adverse outcomes in patients undergoing chemotherapy?","volume":"29","author":"Heng","year":"2020","journal-title":"Eur. J. Cancer Care (Engl.)"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1016\/S0959-8049(02)00081-3","article-title":"Phase I study of a weekly schedule of a fixed dose of cisplatin and escalating doses of paclitaxel in patients with advanced oesophageal cancer","volume":"38","author":"Polee","year":"2002","journal-title":"Eur. J. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2882","DOI":"10.1016\/j.transproceed.2014.09.070","article-title":"Biosimilar granulocyte colony-stimulating factor is effective in reducing the duration of neutropenia after autologous peripheral blood stem cell transplantation","volume":"46","author":"Cioch","year":"2014","journal-title":"Transplant. Proc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1046\/j.1365-2257.1996.00160.x","article-title":"Recurrent septicaemia in a neutropenic patient with typhlitis","volume":"18","author":"Sadullah","year":"1996","journal-title":"Clin. Lab. Haematol."},{"key":"ref_32","unstructured":"Qasim, A., and Nahas, J. (2021). Neutropenic Enterocolitis (Typhlitis), StatPearls Publishing."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1097\/PAS.0000000000000517","article-title":"Neutropenic enterocolitis","volume":"39","author":"Sachak","year":"2015","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1002\/ajh.10272","article-title":"Fatal Bacillus cereus sepsis following resolving neutropenic enterocolitis during the treatment of acute leukemia","volume":"72","author":"Ginsburg","year":"2003","journal-title":"Am. J. Hematol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"112","DOI":"10.3109\/00365548.2012.714906","article-title":"Clinical experience of granulocyte transfusion in the management of neutropenic patients with haematological malignancies and severe infection","volume":"45","author":"Cherif","year":"2013","journal-title":"Scand. J. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1136\/jcp.37.3.335","article-title":"Neutropenic enterocolitis due to Clostridium septicum infection","volume":"37","author":"King","year":"1984","journal-title":"J. Clin. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"492","DOI":"10.3109\/07357909509024913","article-title":"Clostridium septicum bacteremia in a patient with large granular lymphocyte leukemia","volume":"13","author":"Litam","year":"1995","journal-title":"Cancer Investig."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3667","DOI":"10.2169\/internalmedicine.1227-18","article-title":"Fatal neutropenic enterocolitis caused by stenotrophomonas maltophilia: A rare and underrecognized entity","volume":"57","author":"Kaito","year":"2018","journal-title":"Intern. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/S0936-6555(97)80075-1","article-title":"Citrobacter freundii and fatal neutropenic enterocolitis following adjuvant chemotherapy for breast cancer","volume":"9","author":"Clemons","year":"1997","journal-title":"Clin. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1046\/j.1469-0691.2003.00772.x","article-title":"Bacteremia due to Stomatococcos mucilaginosus in neutropenic patients in the setting of a cancer institute","volume":"9","author":"Fanourgiakis","year":"2003","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/0002-9610(86)90547-7","article-title":"Typhlitis: Selective surgical management","volume":"151","author":"Moir","year":"1986","journal-title":"Am. J. Surg."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Yi, H.S., Sym, S.J., Park, J., Cho, E.K., Shin, D.B., and Lee, J.H. (2010). Typhlitis due to mucormycosis after chemotherapy in a patient with acute myeloid leukemia. Leuk. Res., 34.","DOI":"10.1016\/j.leukres.2009.12.022"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1097\/DCR.0000000000001548","article-title":"Neutropenic enterocolitis: Clinical features and outcomes","volume":"63","author":"Ali","year":"2020","journal-title":"Dis. Colon. Rectum."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/S1473-3099(15)00399-0","article-title":"An unusual presentation of neutropenic enterocolitis (typhlitis)","volume":"16","author":"Youngs","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1159\/000506896","article-title":"Neutropenic Enterocolitis in the Treatment of Solid Tumors: A Case Report and Review of the Literature","volume":"13","author":"Cherri","year":"2020","journal-title":"Case Rep. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.ajem.2004.02.014","article-title":"ED presentation of neutropenic enterocolitis in adult patients with acute leukemia","volume":"22","author":"Hsu","year":"2004","journal-title":"Am. J. Emerg. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.ygyno.2004.03.019","article-title":"Chemoradiation with 5-fluorouracil and mitomycin C in the treatment of vulvar squamous cell carcinoma","volume":"93","author":"Mulayim","year":"2004","journal-title":"Gynecol. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Van Eyken, P., Fanni, D., and Gerosa, C. (2014). Ischemic colitis. Colitis a Pract. Approach to Colon Biopsy Interpret, Springer International Publishing.","DOI":"10.1007\/978-3-319-08028-4_8"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Villanacci, V., and Salemme, M. (2014). Microscopic colitis. Colitis a Pract. Approach to Colon Biopsy Interpret, Springer International Publishing.","DOI":"10.1007\/978-3-319-08028-4_11"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1097\/SLA.0b013e3181724fe5","article-title":"Challenges in surgical management of abdominal pain in the neutropenic cancer patient","volume":"248","author":"Badgwell","year":"2008","journal-title":"Ann. Surg."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1002\/bjs.1800760821","article-title":"Surgical management of neutropenic enterocolitis","volume":"76","author":"Koea","year":"1989","journal-title":"Br. J. Surg."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1016\/S0140-6736(01)06884-2","article-title":"Clinical picture: Bacterial translocation in neutropenic sepsis","volume":"358","author":"Cornely","year":"2001","journal-title":"Lancet"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/57\/6\/638\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:19:47Z","timestamp":1760163587000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/57\/6\/638"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,20]]},"references-count":52,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["medicina57060638"],"URL":"https:\/\/doi.org\/10.3390\/medicina57060638","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,20]]}}}