Pathology of Gastrointestinal and Liver Complications of Hematopoietic Stem Cell Transplantation.

CONTEXT.­: Despite advances in therapeutic and preventive measures, hematopoietic stem cell transplant recipients remain at risk for a variety of gastrointestinal and liver complications. OBJECTIVE.­: To detail the pathologic features of the various gastrointestinal and liver complications occurring after hematopoietic stem cell transplantation in relation to their clinical context. The specific complications covered include graft-versus-host disease, mycophenolate mofetil-induced injury, timeline of infections, neutropenic enterocolitis, gastrointestinal thrombotic microangiopathy, sinusoidal obstruction syndrome, hepatic iron overload, and the controversy around cord colitis syndrome. DATA SOURCES.­: The content of this article is based on pertinent peer-reviewed articles in PubMed, relevant textbooks, and on the authors' personal experiences. CONCLUSIONS.­: The final histopathologic diagnosis requires the integration of clinical and histologic findings and the exclusion of other competing causes of injury. Review of the clinical data, including the original disease pretransplant, the type of transplant, the timing of the gastrointestinal and/or liver manifestations, the timing of the biopsy after transplant, the presence of graft-versus-host disease in other organs and sites, the list of drug regimens, and the clinical and laboratory evidence of infection, is the key to reaching the proper histologic diagnosis.

Neutropenic Enterocolitis: New Insights Into a Deadly Entity.

Neutropenic enterocolitis (NE) is a deadly ileocecal-based disease seen in patients with a recent history of chemotherapy. As histology is not included in the current diagnostic criteria, the pathologic features of NE are poorly understood. We undertook a multi-institutional study of NE, and report helpful clinical clues, such as immunosuppression (n=20/20), recent chemotherapy (n=17/18), neutropenia (n=16/18) gastrointestinal symptoms (n=19/19), abnormal imaging studies of the cecum/right colon (n=11/14), and positive microbiological studies (n=13/15). Fever (n=9/15) and sepsis (n=8/16) were also common. Pathologically, the cecum/right colon was always involved (n=17/17), but findings were identified in other bowel segments as well. NE lesions consisted of patchy necrosis (n=18/20), infiltrating organisms (n=17/20), hemorrhage (n=15/20), ulcer (n=15/19), edema (n=15/20), and depletion of inflammatory cells (n=15/20). Seventy-nine percent (n=15/19) of patients with histologically confirmed NE died: 47% (n=7/15) of these deaths were attributed to NE and the remainder to the patients' underlying conditions. Importantly, we observed a clinical diagnostic discordancy rate of 35% (n=9/26): 15% (n=3/20) of histologically confirmed NE were clinically unsuspected, and 26% (n=6/23) of clinically suspected NE represented a different disease process. Alternative diagnoses included unspecified colitis, infection, graft-versus-host disease, relapsed malignancy, mycophenolate injury, appendicitis, and ischemia. The causes of death in patients with NE mimics included unrecognized appendicitis and unrecognized graft-versus-host disease. To improve diagnostic accuracy, we propose that histology be required for a diagnosis of "definitive NE," with other clinically suspicious cases reported as "suspicious for NE" until all other possible diagnoses have been reasonably excluded.

The complication of gastro-enteric fistulisation in neutropenic enterocolitis secondary to aplastic anaemia.

We report the case of a 27-month-old male with an unusual complication of aplastic anaemia and neutropenic enterocolitis. He suffered persistent neutropaenic sepsis and clinical deterioration forced the strategy of matched sibling haematopoietic stem cell transplantation. With engraftment and clinical recovery post-transplant, enteral feeding was re-established. Despite continued improvement the child began to vomit faeculent stomach content. Barium swallow showed gastro-colic and gastro-enteric fistulisation with contrast passing directly from stomach into descending colon and directly into jejunum. Laparotomy confirmed complex fistulae between the gastric body, the splenic flexure of the colon and the jejunum. The diagnosis and management of abdominal pathology secondary to severe pancytopaenia is challenging. Often the patient does not manifest the usual signs of acute abdominal pathology, making the decision to operate and the timing of surgery difficult. Counfounding this is the danger of performing surgery in a pancytopaenic patient. Our case illustrates these challenges and reports the unanticipated finding of a complex gastro-colic fistula.

Recurrent neutropenic enterocolitis in a pediatric patient.

Management of an 8-year-old boy with Hodgkin lymphoma is presented. The patient had several recurrences of neutropenic enterocolitis and eventually required ileocecectomy. A review of the literature on this difficult problem affecting pediatric oncology patients is presented.

Rectal involvement in neutropenic enterocolitis.

Neutropenic enterocolitis is a common gastrointestinal complication in children undergoing chemotherapy for a variety of malignancies. It usually involves ileum and caecum, and involvement of rectum has rarely been reported. The authors report neutropenic enterocolitis in a child undergoing chemotherapy for acute lymphoblastic lymphoma which presented with ileus along with a mass like lesion in the rectum.

Variant neutropenic enterocolitis presenting as acute appendicitis.

BACKGROUND: Neutropenic enterocolitis (NE) is characterized by fever, abdominal pain, and neutropenia. Observed most commonly in relation to solid, hematologic, and lymphoproliferative malignant tumors and their treatment, this disease entity may involve a wide area of the gastrointestinal tract. We report the first case of NE with isolated appendiceal involvement in a non-oncologic neutropenic patient who was managed successfully medically. In addition, we formally recognize neutropenic appendicitis as a variant of NE and differentiate it from acute non-neutropenic appendicitis. METHODS: Case report and review of the pertinent English language literature. CASE REPORT: A 50-year-old man with seronegative large-joint arthritis presented emergently with a one-day history of subjective fever and acute-onset abdominal pain in the setting of recently developed sulfasalazine-induced agranulocytosis. Abdominal examination revealed mild-to-moderate tenderness and rebound tenderness in the right lower quadrant. Computed tomography (CT) of the abdomen demonstrated findings consistent with acute appendicitis. The patient improved clinically with non-operative management including a broad-spectrum antibiotic, with normalization of the white blood cell count four days after initiation of granulocyte-colony stimulating factor therapy. CONCLUSIONS: Given the similarity in clinical presentation and CT imaging in patients with neutropenic and non-neutropenic appendicitis, accurate recognition of neutropenic appendicitis rests on a thorough patient history and a high index of suspicion in febrile neutropenic patients.

Neutropenic enterocolitis.

BACKGROUND: Neutropenic enterocolitis, sometimes called typhilitis, is the most common gastrointestinal infection related to neutropenia, but its rarity, confusing terminology, and protean, non-specific manifestations result in variable approaches to diagnosis and management. METHODS: Review of pertinent English-language literature. RESULTS: The true incidence of neutropenic enterocolitis is unknown, but may be 5% or more among adult patients receiving chemotherapy for solid malignant tumors. The incidence is reported to be slightly lower in children. Estimates are made complex by recent recognition that neutropenia of any cause may be associated with enterocolitis; reports of non-chemotherapy drug-associated cases are increasing. Mortality rates are reported currently to be between 30% to 50%. The exact pathogenesis is also unknown, and may contribute to the varied nomenclature in use. Gut mucosal ulcerations may result from direct drug-related cytotoxicity, or from neutropenia itself. Microbial invasion of the bowel wall proceeds unimpeded. Pathological changes include inflammation and edema, presumably followed by ulceration, transmural necrosis, and perforation. The classic clinical presentation consists of fever, abdominal pain, and neutropenia, but diagnosis is often hindered by subtle or non-specific clinical findings, making computed tomography the linchpin of diagnosis. The wide spectrum of clinical presentation requires an individualized approach to therapy. Medical management, including administration of granulocyte colony-stimulating factor, may be appropriate for patients who do not have gastrointestinal bleeding, peritonitis, or intestinal perforation. Surgical management is generally reserved for patients who fall into any of the exceptional categories, and consists usually of bowel resection and stoma creation. CONCLUSIONS: Neutropenic enterocolitis is a heterogeneous diseazse state with the capacity to affect many areas of the gastrointestinal tract, and disease severity that ranges from mild to fatal. A high index of suspicion is needed for all patients who present with fever and abdominal pain in the setting of neutropenia. Early detection allows a majority of cases to resolve with nonoperative management and supportive care, but surgical intervention is mandatory for peritonitis, bowel perforation, or gastyrointestinal hemorrhage that persists despite correction of coagulopathy.

Neutropenic enterocolitis in breast cancer patient after taxane-containing chemotherapy.

Neutropenic enterocolitis or typhlitis (from the Greek typhlon, meaning caecum) is defined as a necrotizing colitis with inflammation of the cecum and surrounding tissues. Although this condition occurs primarily in severely myelosuppressed and immunosuppressed patients with leukemia, it may also occur in those with other advanced malignancies receiving myelosuppressive chemotherapy. It has been described most recently in patients with solid tumors who receive taxane-based therapy. A 60-year old woman with medullary breast cancer stage IIIB underwent neoadjuvant chemotherapy with TAC (doxetaxele 100 mg/m2, doxorubicin 50 mg/m2 and cyclophosphamide 600 mg/m2). Sixth day after TAC chemotherapy, she had abdominal pain and vomiting. Abdomen CT scan showed diffuse circumferential thickening of ileum wall typical for ileitis, narrowing of the lumen, disturbance of peristaltic. This abdomen CT scan was thought as abnormality pictures of neutropenic enterocolitis. Neutropenic enterocolitis should be considered in patients with abdominal symptoms especially during the granulocyte nadir following chemotherapy. Increased awareness of this rapidly progressive and potentially fatal disease leads to accurate diagnosis and the prompt treatment that can decrease morbidity and mortality.

Neutropenic enterocolitis in children with acute leukemia or aplastic anemia.

Neutropenic enterocolitis (NE) and acute appendicitis are life-threatening conditions that develop in children with severe or prolonged neutropenia secondary to acute leukemia and lymphoma. The medical records of 118 patients who were treated for acute lymphoblastic leukemia (69 patients), acute myelogenous leukemia (22 patients), or aplastic anemia (27 patients) between 1997 and 2006 in our hospital pediatric hematology department were examined retrospectively. NE was diagnosed in 11 patients (age range, 2.5-16 years) on the basis of clinical and laboratory features. Two of these 11 patients had appendicitis in addition to NE. Conservative treatment was favored for all patients, but 1 patient with acute appendicitis underwent surgery. Neutropenic patients with a hematologic malignancy and abdominal pain should receive their diagnoses immediately and undergo treatment. NE and acute appendicitis should always be considered in the differential diagnosis of abdominal pain. Conservative treatment must be chosen initially for patients with NE, and these patients should be evaluated carefully for surgery. The criteria for the surgical process are the same as those for immunocompetent children. In addition, the close monitoring of hematologic factors is necessary.

[Neutropenic enterocolitis in adult patients with acute leukemia or stem cell transplant recipients: study of 7 cases]. / Enterocolitis neutropénica en adultos con leucemia aguda o receptores de un trasplante de progenitores hematopoyéticos: estudio de 7 casos.

BACKGROUND AND OBJECTIVE: Neutropenic enterocolitis (NE) is a complication arising in neutropenic patients with acute leukemia or solid tumours while treated with intensive chemotherapy. The optimal therapeutic procedures have not been well established. PATIENTS AND METHOD: Seven cases of NE diagnosed and treated in a tertiary hospital between 2000 and 2007 are described. Their clinico-biological characteristics, therapeutic procedures and evolution were analysed retrospectively. RESULTS: Five of the patients were males, their median age was 39 years. Acute myeloblastic leukemia was the most frequent diagnosis (5 cases). Two other patients had received an stem cell transplantation. Abdominal pain was present in all patients, diarrhoea in 6, and fever in 5. Microorganisms were isolated from blood cultures in 4 cases (Clostridium septicum, Escherichia coli, Pseudomonas aeruginosa and Aeromonas hydrophila). Abnormal mural thickening of the caecum was observed in the 6 cases in which a computed tomography scan could be performed. The median mural thickness at its maximum section was 11 mm (range: 8-16). All patients first received medical treatment with wide spectrum antibiotics and intestinal rest, and abdominal surgery was indicated in 6 cases after a median time from first symptom of 4 days (range: 0-12). NE was confirmed histologically in all 6 patients. Five patients required admission in Intensive Care Unit and 2 (29%) died as a result of NE. CONCLUSIONS: NE is a severe complication of patients with hematologic malignancies submitted to intensive chemotherapy or receiving stem cell transplantation. Abdominal computed tomography scan is the most valuable diagnostic tool. Prompt surgical intervention may improve the prognosis in patients with NE.

Neutropenic enterocolitis: is there a right timing for surgery? Assessment of a clinical case.

Neutropenic enterocolitis is a severe and potentially life-threatening complication that may affect patients undergoing chemotherapy for acute leukemia or lymphoma. These patients may develop systemic sepsis through bacterial or fungal translocation across the intestinal wall. In many cases neutropenic enterocolitis is confined to the cecum, but the entire colon is sometimes involved. Most patients are treated conservatively because an improvement occurs when the absolute neutrophil count rises. However, a surgical approach consisting of resection of the colon may sometimes be necessary, even in patients with complete aplasia and a high risk of complications. The right time to perform surgery is hard to define. Intestinal wall thickness, evaluated by ultrasound, is an important prognostic factor which could act as a guide to surgical indication. We analyze a case of neutropenic enterocolitis which occurred in a patient with acute myeloid leukemia during chemotherapy and we suggest that, as well as intestinal wall thickness, hemodynamic worsening should be considered an indication for surgery.

Neutropenic enterocolitis.

We report a case of neutropenic enterocolitis diagnosed on computerized tomography abdomen in a 56-year-old man having high-grade non-Hodgkin's lymphoma. After appropriate management, the patient recovered completely.

Systematic review of case reports concerning adults suffering from neutropenic enterocolitis.

INTRODUCTION: Neutropenic enterocolitis (NEC) is a well recognised clinical-pathological and life-threatening complication in patients suffering from several conditions, including solid and haematological malignancies or aplastic anaemia. OBJECTIVE: This review was aimed at evaluating overall NEC mortality rate, describing clinical diagnostic findings and therapeutical interventions reported in the literature and generating a hypothesis regarding factors influencing mortality and surgical intervention. MATERIALS AND METHODS: An advanced search was made in Medline, Embase, Lilacs and Google. Additional strategies included manual search of specific journals. Reports were considered if they described case definition, inclusion and exclusion criteria. RESULTS: 275 cases were selected; 109 were from individual data and 40 from grouped data. Comparing data between case reports and case series revealed no significant differences related to mortality, surgical intervention, sex or age. Higher mortality (chi2 = 7.51 p = 0.006) was found in women (50%) compared to men (28%). No significant difference was found between antibiotic combinations and mortality (chi(2) = 12.85 df 13 p = 0.45). Mortality (chi2 = 3.89 df 1, p = 0.049), surgical intervention (chi2 = 7.64 df 1, p = 0.006) and duration of diarrhoea (chi2 = 4.71 df 1, p = 0.043) were significantly different in 26.4% of individuals using antifungal agents; death occurred in 81% of patients! who did not receive such medication compared to 19% individuals reported as being treated with antifungal agents. CONCLUSION: The current evidence suggests that antifungal agents should be used early in patients suffering from NEC. However, this hypothesis must be evaluated in multi-centric, randomised controlled trials.

Sonographic signs of neutropenic enterocolitis.

AIM: To investigate the sonographic features at time of diagnosis and follow-up in patients with neutropenic enterocolitis. METHODS: The sonographic findings in 14 patients with neutropenic enterocolitis were described and evaluated regarding symptoms and clinical outcome. RESULTS: In all patients with neutropenic enterocolitis, the ileocoecal region was involved with wall thickening >10 mm. A transmural inflammatory pattern, hypervascularity of the thickened bowel wall and free abdominal fluid were the common findings. The sonographically revealed thickness of the bowel wall was associated with lethal outcome (P<0.03). In the 11 surviving patients,the improvement of clinical symptoms was accompanied by progressive reduction of intestinal wall thickness. CONCLUSION: High-end sonography of the bowel is a helpful tool for diagnosis,assessment of prognosis and follow-up of patients with neutropenic enterocolitis.The ultrasonographically revealed bowel thickness reflects the severity and the course of the disease, and seems to be predictive for the clinical outcome.

[Isolated edematous swelling of Bauhin's valve -- sonographically suspected diagnosis of a rare ileocoecal disease]. / Isolierte ödematöse Schwellung der Bauhin-Klappe -- Sonographische Verdachtsdiagnose einer seltenen ileozäkalen Erkrankung.

Isolated edematous swelling of Bauhin's valve is a rare finding in cases of non-specific abdominal complaints in the lower right abdominal quadrant. The differential diagnosis includes entities such as tumours, chronic gastrointestinal inflammation and ileocoecal intussusception as well as specific infections, all of which require individual therapy. Based on two current cases and a review of the literature, aetiology, clinical picture and diagnostic findings of isolated edema of the ileocoecal valve are described. The typical ultrasound findings are presented. Due to its potential of excluding other diseases, modern ultrasound offers promising results in the case of isolated edematous swelling of Bauhin's valve.

Neutropenic enteropathy.

Neutropenic enteropathy (NE) is used to describe the inflammation of the bowel in neutropenic patients under aggressive chemotherapy, mainly for lymphoproliferative and hematologic malignancies. Surgical intervention may be required in patients with the advent of the disease. We report our experience in 7 children with NE who had to be treated surgically. Absolute neutrophil counts were less than 1000/mm3 in all, with positive blood cultures in five patients. Four patients recovered with rapid resolution of neutropenia, while three patients died with persistent neutropenia.