Chapter
from book Care and Prevention of Infection (pp.113-127)

Oncologic Emergencies

Chapter · October 2014with 8 Reads
Abstract
Oncologic emergencies can threaten the lives of children with cancer even before a diagnosis is made. Awareness of common or life-threatening toxicities of cancer and cancer treatment facilitates rapid diagnosis and appropriate immediate management. Clinicians in both primary and tertiary care must recognize and manage five types of oncologic emergency: masses affecting vital organs (superior vena cava [SVC] syndrome, central airway compression [CAC] syndrome, cardiac tamponade, pleural effusion, spinal cord compression, and intracranial hypertension), metabolic emergencies (tumor lysis syndrome [TLS], hypercalcemia, hyponatremia, lactic acidosis, adrenal insufficiency), gastrointestinal emergencies (typhlitis, intestinal obstruction, bowel perforation), and chemotherapy extravasation. For new patients with suspected cancer, a careful history to elicit signs and symptoms, a physical examination, chemistry profile, complete blood count, and chest radiograph are sufficient to rule out an oncologic emergency. Any neurologic deficit, respiratory distress, altered vital signs, abdominal tenderness, abnormal laboratory values, or mediastinal mass on chest radiograph should prompt a thorough and immediate evaluation for life- and organ-threatening emergencies, which are the subject of this chapter.
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  • Article
    Full textFull text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (315K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References. 427 Selected References These references are in PubMed. This may not be the complete list of references from this article. Brosnan CM, Gowing NF. Addison's disease. BMJ. 1996 Apr 27;312(7038):1085–1087. [PMC free article] [PubMed]
  • Article
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  • Article
    Typhlitis or neutropenic enterocolitis (NEC) is a life-threatening condition that occurs in neutropenic patients. Early recognition is crucial owing to high death rate. We present a case of a 54-year-old man, diagnosed with non-Hodgkin lymphoma who received a first cycle of rituximab, cyclophosphamide, hydroxydaunorubicin (doxorubicin), oncovin (vincristine), prednisolone (R-CHOP) chemotherapy 10 days prior presenting. He developed fever, mucositis, watery diarrhoea and right lower quadrant pain with rebound tenderness. He also had neutropenia, with an absolute neutrophil count of zero. CT abdomen confirmed the diagnosis of typhlitis, demonstrating characteristic terminal ileum, caecal and right-sided colon involvement. Moreover, stool PCR was also positive for toxigenic Clostridium difficile. Therefore, the patient was diagnosed with concomitant typhlitis and C difficile-associated diarrhoea (CDAD). He was empirically treated with intravenous cefepime, intravenous metronidazole and oral vancomycin. His symptoms resolved in 10 days. This case illustrated a successful medical treatment of typhlitis in concomitance with CDAD.
  • Article
    Superior vena cava syndrome results from the obstruction of blood flow through the superior vena cava and is most often due to thoracic malignancy. However, benign etiologies are on the rise secondary to more frequent use of intravascular devices such as central venous catheters and pacemakers. Although rarely a medical emergency, the symptoms can be alarming, particularly to the patient. Traditionally, superior vena cava syndrome has been managed with radiotherapy and chemotherapy. But interventional endovascular techniques have made inroads that offer a safe, rapid, and durable response. In many cases, it may be the only reasonable treatment. Because of this, an approach to endovascular treatment of this condition must be in the armamentarium of the interventional radiologist. This review will provide the reader with an insight into the etiology, pathophysiology, and various management principles of superior vena cava syndrome. The focus will be on understanding the techniques used during various endovascular interventions, including angioplasty, stenting, and pharmacomechanical thrombolysis. Discussion will also be centered on possible complications and current evidence as well as controversies regarding these approaches.
  • Article
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  • Article
    Full-text available
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  • Article
    BACKGROUND Lactic acidosis (LA) associated with hematologic malignancies is rare, ominous, and generally occurs in adults. Its pathogenesis is poorly understood.METHODS The authors present one case of childhood lymphoma and two cases of childhood leukemia associated with LA, and they review the available literature. Plasma concentrations of insulin-like growth factors (IGFs), IGF binding proteins (IGFBPs), and tumor necrosis factor (TNF)-α were retrospectively measured to elucidate the pathogenesis of LA.RESULTSLactic acidosis has been reported to date in 28 cases of lymphoma and 25 cases of leukemia, including the authors' cases. Ongoing rapid cellular proliferation was indicated in all leukemia cases. The liver was involved in 43 of the 53 cases, and hypoglycemia was present in 20. The acidosis improved only if the disease responded to chemotherapy. Remission was achieved in only five of the reported cases. In the authors' three cases, LA was associated with altered concentrations of IGFs, IGFBPs, and TNF-α, although causality was not established.CONCLUSIONS Lactic acidosis in association with hematologic malignancies carries an extremely poor prognosis. Because cancer cells have a high rate of glycolysis and produce a large quantity of lactate, this condition may result from an imbalance between lactate production and hepatic lactate utilization. The authors speculate that the IGF system is involved in the pathophysiology of LA in these patients. Only chemotherapy so far has been effective in correcting the acute acidosis in a few patients; however, it has not necessarily improved ultimate outcome. Cancer 2001;92:2237–46. © 2001 American Cancer Society.
  • Article
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  • Article
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  • Article
    To provide an up-to-date review of current literature on the pathophysiology, diagnosis, and management of five key malignancy-related complications: superior vena cava syndrome, malignant pericardial effusion, malignant spinal cord compression, hypercalcemia, and acute tumor lysis syndrome. Database searches and review of relevant medical literature. Malignancy-related complications demand increased attention from intensivists due to their frequency and increasing cancer prevalence. Although such complications portend a poor prognosis, proper acute management can improve short-term outcomes by facilitating either definitive care of the underlying malignancy or the institution of appropriate palliative measures. Knowledge of malignancy-induced complications in critically ill patients expedites the ability of the intensivist to properly manage them. Five complications commonly requiring emergency management are addressed in this review. Specifically, superior vena cava syndrome may warrant radiation, chemotherapy, vascular stenting, or surgical resection. Malignant pericardial effusion may require emergency pericardiocentesis if cardiac tamponade develops. Malignant spinal cord compression demands immediate spinal imaging, glucocorticoids, and either surgery or radiation. Hypercalcemia requires aggressive intravenous hydration and a bisphosphonate. Acute tumor lysis syndrome necessitates intravenous hydration, rasburicase, and management of associated electrolyte abnormalities.
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    Anesthetic management of superior vena cava syndrome carries a possible risk of life-threatening complications such as cardiovascular collapse and complete airway obstruction during anesthesia. Superior vena cava syndrome results from the enlargement of a mediastinal mass and consequent compression of mediastinal structures resulting in impaired blood flow from superior vena cava to the right atrium and venous congestion of face and upper extremity. We report the successful anesthetic management of a 42-year-old man with superior vena cava syndrome posted for cervical lymph node biopsy.
  • Article
    The nervous system can be significantly affected by cancer. Neurologic symptoms are present in 30% to 50% of oncologic patients presenting to the emergency department or in neurologic consultation at teaching hospitals. Evaluation and treatment require collaborative effort between specialties. The causes of neurologic emergencies in patients with cancer are mostly related to effects of cancer, toxicities of treatments, infections, and paraneoplastic syndromes. These complications cause significant morbidity and mortality and require prompt and accurate diagnostic and treatment measures. This article reviews the common neurologic emergencies affecting patients with cancer and discusses epidemiology, clinical presentation, diagnosis, and treatment modalities.
  • Article
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  • Article
    The picture of oncologic emergencies in the intensive care unit has changed over the past decade. The classic emergencies, that is, superior vena cava syndrome, spinal cord compression, tumor lysis syndrome and life-threatening hypercalcemia, are now routinely managed on the general oncology unit or in an outpatient setting. Vigilant monitoring for early signs of complications, proactive interventions to prevent complications, and aggressive management account for this change. Currently, emergent conditions that necessitate intensive care unit admission or transfer in the patient with cancer include respiratory failure, cardiac emergencies, hemorrhagic events and coagulopathies, sepsis, and hemodynamic instability. This article will present the current evidence-based management of these conditions, a brief summary of classic oncologic emergencies, and the role of the critical care nurse in meeting the multidimensional needs of the patient and family during the life-threatening episode, based on Ferrell's quality of life model.
  • Article
    Full-text available
    To review our experience with typhlitis among children treated for acute leukemia. The medical records of children with acute leukemia and typhlitis between 2006 and 2009 were reviewed for demographics and symptoms, and for microbiological and imaging findings. In the 75 children with acute leukemia--54 with acute lymphoblastic leukemia (ALL) and 21 with acute myeloid leukemia (AML)--there were 10 episodes of typhlitis (4.5%) that developed during 221 periods of severe neutropenia. The cumulative risk of typhlitis was 7.4% in patients with ALL and 28.5% in patients with AML. Frequent symptoms were: abdominal pain and tenderness (100% each); fever and nausea (90% each); emesis (80%); diarrhea (50%), and hypotension, peritonitis and abdominal distension (10% each). The median duration of symptoms was 6 days (range: 2-11 days), and that of neutropenia 14 days (range: 3-25 days). All patients were treated medically and none surgically. Two patients died because of typhlitis and sepsis. In our study, the rate of typhlitis among leukemic children was 4.5%; however, the mortality rate was 20%. Thus, rapid identification and timely, aggressive medical intervention are necessary to reduce the morbidity and mortality from typhlitis.
  • Article
    Approximately 50% of patients with metastatic disease develop a malignant pleural effusion (MPE). Prompt clinical evaluation and treatment to achieve successful palliation are the main goals of management of MPE. Optimal treatment is still controversial and there is no universal standard approach. Management options include observation, thoracentesis, indwelling pleural catheter (IPC) or chest tube placement, pleurodesis, and surgical pleurectomy. The treatment for each patient should be based on symptoms, general condition, and life expectancy.
  • Article
    Historic practice recommends slow transfusion for children with chronic anemia and hemoglobin less than 5.0 g/dl due to the theoretical risk of transfusion-associated circulatory overload (TACO). In our pediatric intensive care unit (PICU), we have been utilizing a more liberal transfusion practice in patients without underlying cardiopulmonary disease, and a faster transfusion rate appears safe in this population. Rate of transfusion must be based on multiple factors including convenience, timeliness of procedures and transport to an appropriate care facility, risk of alloimmunization and wastage of blood, stress for the family, and need for PICU monitoring.
  • Article
    Tumor lysis syndrome (TLS) is a serious, sometimes life-threatening oncologic emergency caused by rapid and massive cellular lysis and subsequent release of tumor cell contents and cytokines into the bloodstream. Clinical consequences of TLS include nausea, vomiting, cardiac dysrhythmias and acute kidney injury resulting from hyperuricemia, hyperphosphatemia, or hyperkalemia, and seizures or other symptoms of hypocalcemia. The main principles of TLS management are the identification of high-risk patients, initiation of preventive therapy, early recognition of potential complications and prompt intervention to prevent or mitigate them. As newer and more effective cytotoxic therapies have been developed to treat both hematologic cancers and solid tumors, the incidence of TLS has increased and emerged in a broader spectrum of patients and malignancies. Thus, it is critical for oncologists, nephrologists and other clinicians to stay abreast of new developments in the prevention and management of TLS. The syndrome is classified with the modified Cairo-Bishop classification and patients are stratified into one of the following categories, according to their a priori risk for clinical TLS: negligible risk, low risk, intermediate risk, high risk and established TLS at presentation. This chapter reviews the pathophysiology, epidemiology, risk stratification and management for each risk group, and includes recommendations for risk-adapted monitoring, intravenous fluids and control of elevated phosphorus and uric acid.
  • Article
    In most diseases related to pleural effusion, the fluid analysis yields important diagnostic information, and in certain cases, fluid analysis alone is enough for diagnosis. The many important characteristics of pleural fluid are described, as are other complementary investigations that can assist with the diagnosis of common and rare pleural effusions. For a systematic review of pleural effusion, a literature search for articles on the practical investigation and diagnosis of pleural effusion was done. Articles included guidelines, expert opinion, experimental and nonexperimental studies, literature reviews, and systematic reviews published from May 2003 through June 2009. The search yielded 1 guideline, 2 meta-analyses, 9 literature reviews, 1 randomized control trial, and 9 clinical studies. On the basis of class IIa or class I evidence from these articles, a step by step approach is recommended for investigating a pleural effusion, beginning with assessment of the medical history, clinical examination, radiology, pleural fluid evaluation, and finally, if no diagnosis is forthcoming, a pleural biopsy under image guidance or thoracoscopy.
  • Article
    The integration of all-trans-retinoic acid (ATRA) with anthracycline chemotherapy into up-front regimens for acute promyelocytic leukemia (APL) has produced striking improvements in clinical outcomes, making APL one of the most curable forms of hematologic malignancies in adults. In addition, arsenic trioxide has proven efficacy in relapse and when combined with ATRA in frontline regimens has demonstrated high efficacy in a number of trials and the potential to replace chemotherapy, which would thereby reduce chemotherapy-related adverse events. Cure in APL is also largely dependent on timely and effective supportive care measures that counteract such life-threatening emergencies as coagulopathy and APL differentiation syndrome. The risk of mortality during induction and the risk of relapse following frontline therapy are related to the individual's initial clinical presentation and relapse-risk score at diagnosis; however, these risks are now quite low even in high-risk patients as long as appropriate therapy is initiated expeditiously. Multiple European and North American trials have investigated risk-adapted approaches to the treatment of APL and have reported high success rates. Further refinement of risk-adapted strategies is ongoing and will likely contribute to better patient care. A roundtable conference was conducted to discuss risk-adapted therapy for APL and to develop a consensus statement and approach for clinical oncologists. Expert opinions and evidence-based strategies presented during the roundtable are summarized herein.
  • Article
    Tumour lysis syndrome (TLS) is a life-threatening oncological emergency characterized by metabolic abnormalities including hyperuricaemia, hyperphosphataemia, hyperkalaemia and hypocalcaemia. These metabolic complications predispose the cancer patient to clinical toxicities including renal insufficiency, cardiac arrhythmias, seizures, neurological complications and potentially sudden death. With the increased availability of newer therapeutic targeted agents, such as rasburicase (recombinant urate oxidase), there are no published guidelines on the risk classification of TLS for individual patients at risk of developing this syndrome. We convened an international TLS expert consensus panel to develop guidelines for a medical decision tree to assign low, intermediate and high risk to patients with cancer at risk for TLS. Risk factors included biological evidence of laboratory TLS (LTLS), proliferation, bulk and stage of malignant tumour and renal impairment and/or involvement at the time of TLS diagnosis. An international TLS consensus expert panel of paediatric and adult oncologists, experts in TLS pathophysiology and experts in TLS prophylaxis and management, developed a final model of low, intermediate and high risk TLS classification and associated TLS prophylaxis recommendations.
  • Article
    Hyponatremic encephalopathy is a potentially lethal condition with numerous reports of death or permanent neurological injury. The optimal treatment for hyponatremic encephalopathy remains controversial. We have introduced a unified approach to the treatment of hyponatremic encephalopathy which uses 3% NaCl (513 mEq/L) bolus therapy. Any patient with suspected hyponatremic encephalopathy should receive a 2 cc/kg bolus of 3% NaCl with a maximum of 100 cc, which could be repeated 1-2 times if symptoms persist. The approach results in a controlled and immediate rise in serum sodium with little risk of inadvertent overcorrection.
  • Article
    Full-text available
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  • Article
    The risk of severe complications or death during the initial period of acute leukemia was markedly decreased due to the progress in pediatric oncology and use of simple measures like hyperhydration, forced diuresis, treatment of hyperuricemia, correction of electrolyte and coagulation disturbances and the careful use of antileukemic drugs. The incidence of leukostasis and tumor lysis syndrome depends on absolute initial white blood cell counts and the underlying type of leukemia. Leukapheresis or exchange transfusion may improve the prognosis of high risk patients. Records of all pediatric patients who were newly diagnosed with acute leukemia between 1 / 1998 und 12 / 2008 were retrospectively reviewed for presence of hyperleukocytosis(white blood cell count > 100 GPT / l) at diagnosis and subsequent leukapheresis or exchange transfusion in regards to the clinical outcome. At diagnosis 11 (14 % ) of 77 children with acute leukemia (7 acute lymphoblastic leukemia / ALL; 4 acute myeloblastic leukemia /AML) had hyperleukocytosis. 4 patients (2 ALL, 2 AML) received exchange transfusion and 2 others (1 ALL, 1 AML) underwent leukapheresis. Marked cytoreduction was achieved in all patients within 24 h after therapy initiation. There were no procedure-related adverse events. Symptoms due to hyperleukocytosis markedly improved after cytoreduction. Leukapheresis or exchange transfusion together with conservative management and specific oncological therapy may contribute to rapid leukocyte reduction with acceptable risk. The exact impact of leukapheresis or exchange transfusion on short and long term outcome in pediatric patients with acute leukemia and initial hyperleukocytosis has to be evaluated in future multicentre studies or by the formation of clinical registries.
  • Article
    Full-text available
    Data on the risk factors for typhlitis in children with cancer are limited. The aim of the study was to define the epidemiologic and clinical features of typhlitis and to elucidate predisposing factors for its development. The medical records of pediatric patients with cancer who were diagnosed with typhlitis from 1995 to 2005 were reviewed for clinical, laboratory, and imaging findings. The results were compared with a group of patients with cancer but without typhlitis who were hospitalized during the same period. Of the 843 cancer patients, 42 (5%) had episodes of typhlitis; 32 of them (76%) were being treated for hematologic malignancies. The incidence was highest in patients with Burkitt's lymphoma (15%) and acute myeloblastic leukemia (12%). Work-up included abdominal x-ray in all patients; abdominal ultrasonography and computed tomography were performed in 23% and 11% of patients, respectively. No cases were missed by plain x-ray when compared with computed tomography and ultrasonography. The typhlitis was treated without surgery and survival was 100%. On multivariate analysis, mucositis [odds ratio (OR) = 30.7], stem cell transplantation (OR = 58.9), and receipt of chemotherapy in the previous 2 weeks (OR = 12.9) were significantly associated with the occurrence of typhlitis. We conclude that most children with typhlitis may be treated without surgery in most cases with favorable outcome. A high index of suspicion may be warranted in patients after stem cell transplantation or chemotherapy and patients with mucositis.
  • Article
    The standard management of childhood acute lymphoblastic leukemia with hyperleukocytosis is unclear and its treatment has focused on prompt leukocytoreduction. Cytoreductive therapies have been used for the prevention of tumor lysis syndrome, but the outcomes have been variable and their benefits have not been proven in controlled clinical trials. This condition needs further investigation to develop effective therapeutic strategies. In the present prospective trial, 15 children with acute lymphoblastic leukemia and hyperleukocytosis (range 101-838 x 10(9)/l) were treated with intravenous low-dose prednisone continuous infusion (6 mg/m(2)/24 h). Doses were increased daily and on approximately the fifth day, the full dose of prednisone (60 mg/m(2)/day) was applied. The mean reduction in white blood cell count achieved by this treatment was 34.4% on first day, 56.9% on second day and 76.6% on third day. The treatment was well tolerated. None of the 15 patients developed life-threatening metabolic disorders or required dialysis. Intravenous low-dose prednisone continuous infusion treatment can prevent the progression to tumor lysis syndrome and it may be used for the patients presenting with white blood cell counts between 100 and 400 x 10(9)/l in centers where leukoapheresis is not readily available.
  • Article
    Typhlitis is clinically defined by the triad of neutropenia, abdominal pain, and fever. Radiologic evidence of colonic inflammation supports the diagnosis. We report a single United Kingdom tertiary center experience with management and outcome of typhlitis for 5 years. Hospital computerized records were screened for ultrasound or computerized tomographic scan requests for abdominal pain for all oncology inpatients (2001-2005). Retrospective case note analysis was used to collect clinical data for patients with features of typhlitis. The incidence of typhlitis among oncology inpatients was 6.7% (40/596) among oncology inpatients and 11.6% (40/345) among those on chemotherapy. Eighteen children had radiologically confirmed typhlitis, and 22 had clinical features alone. Most (93%) patients responded to conservative management. Eighteen children had a variable period of bowel rest, including 12 patients who were supported with total parenteral nutrition. Three patients had laparotomy that revealed extensive colonic bowel necrosis (1), perforated gastric ulcer (1), and a perforated appendix (1). A single child died of fulminant gram-negative sepsis without surgical intervention. The diagnosis of typhlitis was based on clinical features, supported by radiologic evidence in almost half of the study group. Surgical intervention should be reserved for specific complications or where another surgical pathologic condition cannot reasonably be ruled out.
  • Article
    Superior vena cava (SVC) syndrome is a historic entity that is reemerging as an important, albeit still uncommon, contemporary vascular disease condition. The causes of SVC syndrome have evolved dramatically over the last century: whereas the majority of originally described cases were due to infection, contemporary presentations are now predominantly associated with the presence of an intravascular device and/or mediastinal malignancy. Multiple underlying pathologic mechanisms often coexist to confer risk for SVC syndrome. Although the diagnosis is still best made at the bedside, advanced imaging modalities may be used to clarify etiology, grade severity, and facilitate intervention. Treatment of SVC syndrome often requires a combination of noninvasive and invasive therapies. With regard to invasive strategies, endovascular approaches to revascularization are now considered first-line given their relative safety and efficacy. Fortunately, both endovascular and open surgical interventions can offer definitive therapy in a majority of cases.
  • Article
    Acute lymphoblastic leukemia (ALL) remains one of the most common malignancies of childhood. Between April 1999 and August 2004, 9 of 207 patients treated at a Tertiary Oncology Service for ALL presented with Intracranial Hypertension (IH). Seven of the patients met the diagnostic criteria for Idiopathic Intracranial Hypertension (IIH). Four of the patients were treated with cerebrospinal fluid (CSF) drainage alone and four required Acetazolamide. Two of the four patients who were treated with Acetazolamide required subsequently a lumbar-peritoneal (LP) shunt. One patient succumbed to his disease before receiving any specific treatment.
  • Article
    To assess the evidence for the current standard of practice of using empirical antifungal treatment in febrile neutropenic cancer patients. Systematic review and meta-analysis of randomised controlled trials comparing empirical or preemptive antifungal treatment with placebo, no intervention, or another antifungal. The primary outcomes were all-cause mortality and invasive fungal infections (IFI) (documented or probable). Relative risks (RR) with 95% confidence intervals (CI) were pooled. Six trials assessed the efficacy of empirical treatment compared to no treatment and one compared empirical to preemptive therapy. Empirical treatment did not decrease mortality significantly (RR 0.82, 95% CI 0.50-1.34), but significantly decreased IFIs (RR 0.25, 0.12-0.54). Twenty-three trials assessed the efficiency of different antifungals. All-cause mortality was lower with azoles compared to amphotericin B (AB) (RR 0.81, 0.65-1.01); IFI rates were not different while adverse events were less frequent with azoles (RR 0.40; 0.34-0.66). Liposomal AB was associated with lower mortality and IFIs than other AB formulations (RR 1.57, 1.10-2.23 and 1.48, 0.98-2.25, respectively). Caspofungin was associated with fewer adverse events, but otherwise comparable to liposomal AB. All trials included patients with haematological malignancies. Major limitations included per-protocol analysis, non-blinded design and inconsistent definitions of IFIs. Empirical antifungal treatment is associated with a lower rate of IFIs but no significant difference in overall mortality. The assessment of IFIs in these trials may have been biased, offering only weak support to standard practice. Azoles, liposomal amphotericin B or caspofungin should be preferred. Pre-emptive antifungal therapy should be considered and further investigated.
  • Article
    Typhlitis is a necrotizing inflammatory disease of the cecum, usually with secondary infection. It is most often found in acute leukemia patients on chemotherapy but has also been reported in other patients on chemotherapeutic drugs. Diagnostic features of typhlitis have been reported on plain radiographs, barium enema, angiography, CT, and one other reported case with ultrasound. We report three cases of typhlitis with a characteristic echogenic thickening of the mucosa on ultrasound. The sonographic findings in the one previous report were identical to those of our three cases. We believe that the sonographic findings of typhlitis are unique and that ultrasound offers an easy noninvasive method of diagnosing this potentially lethal disease.
  • Article
    The physiology of the release of antidiuretic hormone (ADH) from the posterior pituitary is briefly reviewed. The importance of both osmolar and non-osmolar stimuli is emphasised. Osmolar and non-osmolar factors usually reinforce each other; for example, hydropenia leads to hyperosmolality and hypovolaemia, both promoting ADH release, while hydration has the opposite effect. In disease, osmolar and non-osmolar factors may become dissociated leading to baroreceptor-mediated ADH release in the presence of hyponatraemia and hypo-osmolality. Examples include heart failure, glucocorticoid or thyroxine deficiency, hepatic cirrhosis and nephrotic syndrome with or without the superimposed effect of diuretics, i.e. conditions in which circulatory, and in particular effective arterial, volume is reduced. It is dangerous to label such conditions as 'inappropriate' secretion of ADH since the maintenance of circulating volume is at least as important a physiological requirement as the defence of tonicity. The syndrome of inappropriate secretion of ADH (SIADH) is uncommon in childhood and should only be diagnosed when physiological release of ADH in response to non-osmolar as well as osmolar factors has been excluded. Criteria for the correct identification of SIADH are discussed; the presence of continuing urinary sodium excretion in the presence of hyponatraemia and hypo-osmolality is essential to the diagnosis. SIADH in children is usually due to intracranial disease or injury. The mainstay of treatment is water restriction which reverses all the physiological abnormalities of the condition. Hypertonic saline is rarely indicated for the short-term control of neurological manifestations such as seizures. Drugs have little or no place in the treatment of SIADH in children.(ABSTRACT TRUNCATED AT 250 WORDS)
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    A previously healthy young child presented with a large pericardial effusion and cardiac tamponade. The chest radiography was key to the recognition of the pericardial effusion. Cytologic examination of the pericardial fluid ultimately established the diagnosis of acute monoblastic leukemia in the absence of associated clinical or laboratory findings. The pericardial fluid was vital for leukemic cell classification because the bone marrow has hypocellular and non-diagnostic. This presentation of acute monoblastic leukemia is very rare, and in the three previously reported pediatric cases has been associated either with peripheral blasts or a history of preleukemia. When the cardiac configuration suggests pericardial effusion in a previously healthy young child, the diagnosis of new onset leukemia should be considered.
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    Hypercalcemia complicating malignancy is a frequent complication in adults, but little has been published about the pathogenesis or the true incidence of hypercalcemia in children with cancer. Hypercalcemia developing in childhood malignancies was studied retrospectively at St. Jude Children's Research Hospital to determine its incidence, the timing of its presentation, and its response to therapy. Over a 29-year period, 25 children (median age, 9.5 years) had been diagnosed and treated for hypercalcemia that occurred during the course of their malignancy. These 25 represented 0.4% of the total number of children treated for cancer at the institution during that period. Their malignancies comprised acute leukemias (11; 0.6%), rhabdomyosarcoma (4; 1.2%), malignant rhabdoid tumor (2), Hodgkin disease (1), non-Hodgkin lymphoma (1), hepatoblastoma (2), neuroblastoma (1), brain tumor (1), angiosarcoma (1), and a solid malignant tumor of undetermined type. Patients with acute lymphoblastic leukemia were more likely to present with hypercalcemia at the time of their initial diagnosis and to achieve resolution of this complication, whereas patients with solid tumors presented with hypercalcemia later in the course of their disease and had hypercalcemia that was more resistant to therapy. In contrast to adults with cancer, hypercalcemia of malignancy is extremely rare in children.
  • Article
    Many protocols for treating children with early B-cell lineage acute lymphoblastic leukemia use 28 consecutive days of high-dose glucocorticoids during induction therapy. We prospectively studied the effects of this therapy on adrenal function. Ten children with early B-cell lineage acute lymphoblastic leukemia were evaluated by cosyntropin (corticotropin (1-24)) stimulation testing before initiation of dexamethasone therapy and every 4 weeks thereafter until adrenal function returned to normal. All 10 patients had normal adrenal function before dexamethasone treatment and insufficient adrenal responses 24 hours after completing therapy. Each child felt ill for 2 to 4 weeks after completing therapy. Although 7 patients recovered normal adrenal function after 4 weeks, 3 patients did not have normal adrenal function until 8 weeks after discontinuing therapy. Statistically significant differences in both basal and corticotropin-stimulated cortisol levels were noted when comparing tests performed at baseline, 24 hours after completing therapy, and 4 weeks after completing therapy. High-dose dexamethasone therapy, a standard treatment for early B-cell acute lymphoblastic leukemia, can cause adrenal insufficiency lasting more than 4 weeks after cessation of treatment. This problem might be avoided by tapering doses of glucocorticoids and providing supplemental glucocorticoids during periods of increased stress.
  • Article
    Acute hyperleukocytic leukemias (AHL) are associated with a very high early mortality rate mostly due to respiratory failure or intracranial bleeding. The pathophysiological process leading to these complications is called leukostasis but the biological mechanisms underlying its development and progression remain unclear. Although traditionally related to "over-crowding" of leukemic blasts in the capillaries of the microcirculation, leukostasis is likely to result from direct endothelial cell damage. This damage is probably mediated by soluble cytokines released during the interaction between leukemic cells and vascular endothelium and by the subsequent migration of leukemic blasts in the perivascular space. Leukemic cell's ability to respond to chemotactic cytokines and their expression of specific adhesion molecules are probably more important in determining whether leukostasis will develop than the number of circulating blasts. This could explain why leukostasis does not develop in all patients with AHL. The identification of the adhesion molecules, cytokines and receptors mediating endothelial cell damage in AHL should become a priority if therapeutic improvements are desired. Leukapheresis is widely used but it is unclear whether it provides additional benefit to a simpler and less invasive intervention with allopurinol, hydroxyurea and intravenous fluids. Cranial irradiation is not generally recommended. Induction chemotherapy should be started without delay. It is hoped that specific pharmacological inhibitors of the interaction between leukemic cells and vascular endothelium will result in an improved outcome for this very high-risk population.
  • Article
    To develop more effective chemotherapy regimens for childhood acute myelogenous leukemia (AML). Between June 1991 and December 1996, we administered the nucleoside analog 2-chlorodeoxyadenosine (2-CDA) to 73 children with primary AML and 20 children with secondary AML or myelodysplastic syndrome (MDS). Patients received one or two 5-day courses of 2-CDA (8.9 mg/m(2)/d) given by continuous infusion. All patients then received one to three courses of daunomycin, cytarabine, and etoposide (DAV) remission induction therapy. Seventy-two patients with primary AML were assessable for response. Their rate of complete remission (CR) was 24% after one course of 2-CDA, 40% after two courses of 2-CDA, and 78% after DAV therapy. Of the 57 patients who entered CR, 11 subsequently underwent allogeneic bone marrow transplantation (BMT), and 40 underwent autologous BMT. Twenty-nine patients remain in continuous CR after BMT. Two patients remain in CR after chemotherapy only. The 5-year event-free survival (EFS) estimate was 40% (SE = 0.080%). Patients with French-American-British (FAB) M5 AML had a higher rate of CR after treatment with 2-CDA (45% after one course and 70.6% after two courses) than did others (P =.002). In contrast, no patient with FAB M7 AML (n = 10) entered CR after treatment with 2-CDA. Similarly, no patient with primary MDS (n = 6) responded to 2-CDA. Seven patients with secondary AML or MDS (n = 14) had a partial response to one course of 2-CDA. This agent was well tolerated, and its toxicity was acceptable. Future trials should examine the effectiveness of 2-CDA given in combination with other agents effective against AML.