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Cancer Treatment Reviews Feb 2017Splenic irradiation (SI) is a palliative treatment option for symptomatic splenomegaly (i.e. for pain, early satiety, pancytopenia from sequestration) secondary to... (Meta-Analysis)
Meta-Analysis Review
Splenic irradiation (SI) is a palliative treatment option for symptomatic splenomegaly (i.e. for pain, early satiety, pancytopenia from sequestration) secondary to hematologic malignancies and disorders. The purpose of the current article is to review the literature on SI for hematologic malignancies and disorders, including: (1) patient selection and optimal technique; (2) efficacy of SI; and (3) toxicities of SI. PICOS/PRISMA methods are used to select 27 articles including 766 courses of SI for 486 patients from 1960 to 2016. The most common cancers treated included chronic lymphocytic leukemia and myeloproliferative disorders; the most common regimen was 10Gy in 1Gy fractions over two weeks, and 27% of patients received retreatment. A partial or complete response (for symptoms, lab abnormalities) was obtained in 85-90% of treated patients, and 30% were retreated within 6-12months. There was no correlation between biologically equivalent dose of radiation therapy and response duration, pain relief, spleen reduction, or cytopenia improvement (r all <0.4); therefore, lower doses (e.g. 5Gy in 5 fractions) may be as effective as higher doses. Grade 3-4 toxicity (typically leukopenia, infection) was noted in 22% of courses, with grade 5 toxicity in 0.7% of courses. All grade 5 toxicities were due to either thrombocytopenia with hemorrhage or leukopenia with sepsis (or a combination of both); they were sequelae of cancer and not directly caused by SI. In summary, SI is generally a safe and efficacious method for treating patients with symptomatic splenomegaly.
Topics: Aged; Dose Fractionation, Radiation; Hematologic Neoplasms; Humans; Middle Aged; Patient Selection; Radiotherapy; Spleen; Splenomegaly; Treatment Outcome
PubMed: 28063304
DOI: 10.1016/j.ctrv.2016.11.016 -
Archives of Disease in Childhood Oct 2016Leukaemia is the most common cancer of childhood, accounting for a third of cases. In order to assist clinicians in its early detection, we systematically reviewed all... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Leukaemia is the most common cancer of childhood, accounting for a third of cases. In order to assist clinicians in its early detection, we systematically reviewed all existing data on its clinical presentation and estimated the frequency of signs and symptoms presenting at or prior to diagnosis.
DESIGN
We searched MEDLINE and EMBASE for all studies describing presenting features of leukaemia in children (0-18 years) without date or language restriction, and, when appropriate, meta-analysed data from the included studies.
RESULTS
We screened 12 303 abstracts for eligibility and included 33 studies (n=3084) in the analysis. All were cohort studies without control groups. 95 presenting signs and symptoms were identified and ranked according to frequency. Five features were present in >50% of children: hepatomegaly (64%), splenomegaly (61%), pallor (54%), fever (53%) and bruising (52%). An additional eight features were present in a third to a half of children: recurrent infections (49%), fatigue (46%), limb pain (43%), hepatosplenomegaly (42%), bruising/petechiae (42%), lymphadenopathy (41%), bleeding tendency (38%) and rash (35%). 6% of children were asymptomatic on diagnosis.
CONCLUSIONS
Over 50% of children with leukaemia have palpable livers, palpable spleens, pallor, fever or bruising on diagnosis. Abdominal symptoms such as anorexia, weight loss, abdominal pain and abdominal distension are common. Musculoskeletal symptoms such as limp and joint pain also feature prominently. Children with unexplained illness require a thorough history and focused clinical examination, which should include abdominal palpation, palpation for lymphadenopathy and careful scrutiny of the skin. Occurrence of multiple symptoms and signs should alert clinicians to possible leukaemia.
Topics: Abdominal Pain; Adolescent; Child; Child, Preschool; Contusions; Early Detection of Cancer; Exanthema; Fever; Gastrointestinal Diseases; Hemorrhage; Hepatomegaly; Humans; Infant; Infant, Newborn; Infections; Leukemia; Musculoskeletal Diseases; Recurrence; Skin Diseases; Splenomegaly
PubMed: 27647842
DOI: 10.1136/archdischild-2016-311251 -
The Lancet. Haematology Apr 2016Multicentric Castleman's disease describes a group of poorly understood lymphoproliferative disorders driven by proinflammatory hypercytokinaemia. Patients have... (Review)
Review
BACKGROUND
Multicentric Castleman's disease describes a group of poorly understood lymphoproliferative disorders driven by proinflammatory hypercytokinaemia. Patients have heterogeneous clinical features, characteristic lymph node histopathology, and often deadly multiple organ dysfunction. Human herpesvirus 8 (HHV8) causes multicentric Castleman's disease in immunosuppressed patients. The cause of HHV8-negative multicentric Castleman's disease is idiopathic; such cases are called idiopathic multicentric Castleman's disease. An absence of centralised information about idiopathic multicentric Castleman's disease represents a major challenge for clinicians and researchers. We aimed to characterise clinical features of, treatments for, and outcomes of idiopathic multicentric Castleman's disease.
METHODS
We did a systematic literature review and searched PubMed, the Cochrane database, and ClinicalTrials.gov from January, 1995, with keywords including "Castleman's disease" and "giant lymph node hyperplasia". Inclusion criteria were pathology-confirmed Castleman's disease in multiple nodes and minimum clinical and treatment information on individual patients. Patients with HHV8 or HIV infection or diseases known to cause Castleman-like histopathology were excluded.
FINDINGS
Our search identified 626 (33%) patients with HHV8-negative multicentric Castleman's disease from 1923 cases of multicentric Castleman's disease. 128 patients with idiopathic multicentric Castleman's disease met all inclusion criteria for the systematic review. Furthermore, aggregated data for 127 patients with idiopathic multicentric Castleman's disease were presented from clinical trials, which were excluded from primary analyses because patient-level data were not available. Clinical features of idiopathic multicentric Castleman's disease included multicentric lymphadenopathy (128/128), anaemia (79/91), elevated C-reactive protein (65/79), hypergammaglobulinaemia (63/82), hypoalbuminaemia (57/63), elevated interleukin 6 (57/63), hepatomegaly or splenomegaly (52/67), fever (33/64), oedema, ascites, anasarca, or a combination (29/37), elevated soluble interleukin 2 receptor (20/21), and elevated VEGF (16/20). First-line treatments for idiopathic multicentric Castleman's disease included corticosteroids (47/128 [37%]), cytotoxic chemotherapy (47/128 [37%]), and anti-interleukin 6 therapy (11/128 [9%]). 49 (42%) of 116 patients failed first-line therapy, 2-year survival was 88% (95% CI 81-95; 114 total patients, 12 events, 36 censored), and 27 (22%) of 121 patients died by the end of their observed follow-up (median 29 months [IQR 12-50]). 24 (19%) of 128 patients with idiopathic multicentric Castleman's disease had a diagnosis of a separate malignant disease, significantly higher than the frequency expected in age-matched controls (6%).
INTERPRETATION
Our systematic review provides comprehensive information about clinical features, treatment, and outcomes of idiopathic multicentric Castleman's disease, which accounts for at least 33% of all cases of multicentric Castleman's disease. Our findings will assist with prompt recognition, diagnostic criteria development, and effective management of the disease.
FUNDING
None.
Topics: Castleman Disease; HIV Infections; Herpesviridae Infections; Herpesvirus 8, Human; Humans; Lymph Nodes
PubMed: 27063975
DOI: 10.1016/S2352-3026(16)00006-5 -
Clinics and Research in Hepatology and... Feb 2019Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of rare genetic disorders associated with bile acid secretion or transport defects. This is...
BACKGROUND AND AIMS
Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of rare genetic disorders associated with bile acid secretion or transport defects. This is the first systematic review of the epidemiology, natural history and burden of PFIC.
METHODS
MEDLINE and Embase were searched for publications on PFIC prevalence, incidence or natural history, and the economic burden or health-related quality of life (HRQoL) of patients with PFIC. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.
RESULTS
Of 1269 records screened, 20 were eligible (epidemiology, 17; humanistic burden, 5; both, 2). Incidence of intrahepatic cholestasis, including but not limited to PFIC, was 1/18 000 live births in one study that did not use genetic testing. In two studies of infants and children (2-18 years) with cholestasis, 12-13% had genetically diagnosed PFIC. Of the three main PFIC subtypes, PFIC2 was the most common (21-91% of patients). Common symptoms (e.g. pruritus, jaundice, hepatomegaly, splenomegaly) generally appeared at about 3 months of age and tended to emerge earliest in patients with PFIC2. Patients reported that pruritus was often severe and led to dermal damage and reduced HRQoL. Disease progression led to complications including liver failure and hepatocellular carcinoma, with 20-83% of patients requiring liver transplantation. Mortality was 0-87% across 10 studies (treatment varied among studies), with a median age at death of ~4 years in one study.
CONCLUSIONS
Patients with PFIC face debilitating symptoms and poor prognosis. Further research is needed to inform patient management and clinical trial design. Published data on the epidemiology and socioeconomic burden of PFIC is limited.
Topics: Cholestasis, Intrahepatic; Humans
PubMed: 30236549
DOI: 10.1016/j.clinre.2018.07.010 -
Orphanet Journal of Rare Diseases Jun 2021Progressive familial intrahepatic cholestasis is a rare, heterogeneous group of liver disorders of autosomal recessive inheritance, characterised by an early onset of... (Review)
Review
BACKGROUND
Progressive familial intrahepatic cholestasis is a rare, heterogeneous group of liver disorders of autosomal recessive inheritance, characterised by an early onset of cholestasis with pruritus and malabsorption, which rapidly progresses, eventually culminating in liver failure. For children and their parents, PFIC is an extremely distressing disease. Significant pruritus can lead to severe cutaneous mutilation and may affect many activities of daily living through loss of sleep, irritability, poor attention, and impaired school performance.
METHODS
Databases including MEDLINE and Embase were searched for publications on PFIC prevalence, incidence or natural history, and the economic burden or health-related quality of life of patients with PFIC. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.
RESULTS
Three systematic reviews and twenty-two studies were eligible for inclusion for the epidemiology of PFIC including a total of 2603 patients. Study periods ranged from 3 to 33 years. Local population prevalence of PFIC was reported in three studies, ranging from 9.0 to 12.0% of children admitted with cholestasis, acute liver failure, or splenomegaly. The most detailed data come from the NAPPED study where native liver survival of >15 years is predicted in PFIC2 patients with a serum bile acid concentration below 102 µmol/L following bile diversion surgery. Burden of disease was mainly reported through health-related quality of life (HRQL), rates of surgery and survival. Rates of biliary diversion and liver transplant varied widely depending on study period, sample size and PFIC type, with many patients have multiple surgeries and progressing to liver transplant. This renders data unsuitable for comparison.
CONCLUSION
Using robust and transparent methods, this systematic review summarises our current knowledge of PFIC. The epidemiological overview is highly mixed and dependent on presentation and PFIC subtype. Only two studies reported HRQL and mortality results were variable across different subtypes. Lack of data and extensive heterogeneity severely limit understanding across this disease area, particularly variation around and within subtypes.
Topics: Activities of Daily Living; Child; Cholestasis; Cholestasis, Intrahepatic; Humans; Quality of Life
PubMed: 34082807
DOI: 10.1186/s13023-021-01884-4 -
World Journal of Surgery Feb 2021To review the evidence regarding the outcomes of laparoscopic techniques in cases of splenomegaly. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To review the evidence regarding the outcomes of laparoscopic techniques in cases of splenomegaly.
BACKGROUND
Endoscopic approaches such as laparoscopic, hand-assisted laparoscopic, and robotic surgery are commonly used for splenectomy, but the advantages in cases of splenomegaly are controversial.
REVIEW METHODS
We conducted a systematic review using PRISMA guidelines. PubMed/MEDLINE, ScienceDirect, Scopus, Cochrane Library, and Web of Science were searched up to February 2020.
RESULTS
Nineteen studies were included for meta-analysis. In relation to laparoscopic splenectomy (LS) versus open splenectomy (OS), 12 studies revealed a significant reduction in length of hospital stay (LOS) of 3.3 days (p = <0.01) in the LS subgroup. Operative time was higher by 44.4 min (p < 0.01) in the LS group. Blood loss was higher in OS 146.2 cc (p = <0.01). No differences were found regarding morbimortality. The global conversion rate was 19.56%. Five studies compared LS and hand-assisted laparosocpic splenectomy (HALS), but no differences were observed in LOS, blood loss, or complications. HALS had a significantly reduced conversion rate (p < 0.01). In two studies that compared HALS and OS (n = 66), HALS showed a decrease in LOS of 4.5 days (p < 0.01) and increase of 44 min in operative time (p < 0.01), while OS had a significantly higher blood loss of 448 cc (p = 0.01). No differences were found in the complication rate.
CONCLUSION
LS is a safe approach for splenomegaly, with clear clinical benefits. HALS has a lower conversion rate. Higher-quality confirmatory trials with standardized splenomegaly grading are needed before definitive recommendations can be provided. Prospero registration number: CRD42019125251.
Topics: Blood Loss, Surgical; Humans; Laparoscopy; Length of Stay; Operative Time; Postoperative Complications; Splenectomy; Splenomegaly; Treatment Outcome
PubMed: 33179126
DOI: 10.1007/s00268-020-05839-x -
Malaria Journal Apr 2015The hyper-reactive malarial splenomegaly syndrome (HMS) is a leading cause of massive splenomegaly in malaria-endemic countries. HMS is caused by a chronic antigenic... (Review)
Review
BACKGROUND
The hyper-reactive malarial splenomegaly syndrome (HMS) is a leading cause of massive splenomegaly in malaria-endemic countries. HMS is caused by a chronic antigenic stimulation derived from the malaria parasite. Classic Fakunle's major criteria for case definition are: persistent gross splenomegaly, elevated anti-malarial antibodies, IgM titre >2 SD above the local mean value and favourable response to long-term malaria prophylaxis. The syndrome is fatal if left untreated. The aim of this study is to systematically review the literature about HMS, particularly focussing on case definition, epidemiology and management.
METHODS
The search strategy was based on the following database sources: Pubmed, EmBase, Scopus. Search was done in March, 2014 and limited to English, Spanish, Italian, French, and Portuguese.
RESULTS
Papers detected were 149, of which 89 were included. Splenomegaly was variably defined and the criterion of increased IgM was not always respected. The highest prevalence was reported in Papua New Guinea (up to 80%). In different African countries, 31 to 76% of all splenomegalies were caused by HMS. Fatality rate reached 36% in three years. The most frequent anti-malarial treatments administered were weekly chloroquine or daily proguanil from a minimum of one month to lifelong. In non-endemic countries, a few authors opted for a single, short anti-malarial treatment. All treated patients with no further exposure improved. Cases not completely fulfilling Fakunle's criteria and therefore untreated, subsequently evolved into HMS. It seems thus appropriate to treat incomplete or 'early' HMS, too.
CONCLUSIONS
For patients not re-exposed to endemic areas, a short course of treatment is sufficient, showing that eradicating the infection is sufficient to cure HMS. Longer (probably lifelong) courses, or intermittent treatments, are required for those who remain exposed. Splenectomy, associated with high mortality, should be strictly limited to cases not responding to medical treatment.
Topics: Antibodies, Protozoan; Antimalarials; Humans; Immunoglobulin M; Malaria; Prevalence; Splenomegaly
PubMed: 25925423
DOI: 10.1186/s12936-015-0694-3 -
Orphanet Journal of Rare Diseases Jun 2019Congenital tuberculosis is rare and carries a high mortality rate. Our objective was to summarize the current experience of the diagnosis and treatment of patients with... (Review)
Review
BACKGROUND
Congenital tuberculosis is rare and carries a high mortality rate. Our objective was to summarize the current experience of the diagnosis and treatment of patients with congenital tuberculosis.
METHODS
In total, 73 reported cases of congenital tuberculosis published in Chinese and 19 patients with congenital tuberculosis admitted to West China Second University Hospital, Sichuan University, were retrospectively reviewed.
RESULTS
Sixty-four male and 28 female patients were identified. The majority of the patients were less than 3 weeks old at the time of presentation (range, 0-67 days). With regard to the tuberculosis type, 89 patients had pulmonary tuberculosis, and 20 patients had hepatic tuberculosis. There was active tuberculosis in 71 mothers, no tuberculosis in 12 mothers, and an unknown history of tuberculosis in 9 mothers. Fever, cyanosis, jaundice, shortness of breath, cough, pulmonary moist rales, hepatomegaly, splenomegaly and abdominal distention were the main clinical symptoms at the time of presentation. The abnormal ratios of chest, abdomen and head radiographic images were 97.53, 75 and 81.25%, respectively. The positive rates of acid-fast staining of sputum smears and tuberculosis bacillus DNA were 62.50 and 66.67%, respectively. The misdiagnosis rate was 59.78%. The overall mortality due to congenital tuberculosis was 43.48%. Respiratory failure was the most common cause of death. Sixty-five patients received anti-tuberculosis therapy, and of those, only 16 (15.38%) died.
CONCLUSIONS
The clinical manifestations and radiographic findings of congenital tuberculosis are nonspecific. It is important to thoroughly evaluate the mothers of infants with suspected congenital tuberculosis. Good outcomes can be achieved in infants with the early identification of congenital tuberculosis and early administration of anti-tuberculosis treatment.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Respiratory Insufficiency; Retrospective Studies; Tuberculosis; Tuberculosis, Hepatic; Tuberculosis, Pulmonary; Young Adult
PubMed: 31182120
DOI: 10.1186/s13023-019-1101-x -
Journal of Global Health Dec 2015Children suffer the highest burden of enteric fever among populations in South Asian countries. The clinical features are non-specific, vary in populations, and are... (Review)
Review
BACKGROUND
Children suffer the highest burden of enteric fever among populations in South Asian countries. The clinical features are non-specific, vary in populations, and are often difficult to distinguish clinically from other febrile illnesses, leading to delayed or inappropriate diagnosis and treatment. We undertook a systematic review to assess the clinical profile and laboratory features of enteric fever across age groups, economic regions, level of care and antibiotic susceptibility patterns.
METHODS
We searched PubMed (January 1964-December 2013) for studies describing clinical features in defined cohorts of patients over varying time periods. Studies with all culture-confirmed cases or those with at least 50% culture-confirmed cases were included. 242 reports were screened out of 4398 relevant articles and 180 reports were included for final review.
RESULTS
96% of studies were from an urban location, 96% were hospital-based studies, with 41% of studies were from South Asia. Common clinical features in hospitalized children include high-grade fever, coated tongue, anaemia, nausea/vomiting, diarrhea, constipation, hepatomegaly, splenomegaly neutrophilia, abdominal distension and GI bleeding. In adults' nausea/vomiting, thrombocytopenia and GI perforation predominate. The case-fatality rate in children under 5 years is higher than school aged children and adolescents, and is highest in Sub Saharan Africa and North Africa/Middle East regions. Multi-drug resistant enteric fever has higher rates of complications than drug sensitive enteric fever, but case fatality rates were comparable in both.
CONCLUSIONS
Our findings indicate variability in disease presentation in adults compared to children, in different regions and in resistant vs sensitive cases. Majority of studies are from hospitalized cases, and are not disaggregated by age. Despite higher complications in MDR enteric fever, case fatality rate is comparable to sensitive cases, with an overall hospital based CFR of 2%, which is similar to recent global estimates. This review underscores the importance of further epidemiological studies in community settings among children and adults, and the need for further preventable measures to curtail the burden of disease.
Topics: Adolescent; Adult; Africa; Asia; Child; Child, Preschool; Diarrhea; Female; Global Health; Humans; Incidence; Laboratories; Male; Paratyphoid Fever; Salmonella paratyphi A; Salmonella typhi; Typhoid Fever
PubMed: 26649174
DOI: 10.7189/jogh.05.020407 -
Blood Cancer Journal Jul 2021Myelofibrosis is a myeloproliferative neoplasm associated with constitutional symptoms, increasing splenomegaly, and worsening cytopenias. Janus kinase (JAK) inhibitors... (Meta-Analysis)
Meta-Analysis
Myelofibrosis is a myeloproliferative neoplasm associated with constitutional symptoms, increasing splenomegaly, and worsening cytopenias. Janus kinase (JAK) inhibitors have been used for the treatment of myelofibrosis for several years, but there is a lack of comparative information between those treatments. A systematic review and network meta-analysis was performed on randomized controlled trials in patients with myelofibrosis receiving JAK inhibitor or placebo or control. Primary outcomes were efficacy on spleen volume reduction and total symptom score reduction. Additional analyses were conducted on anemia and thrombopenia events. Seven studies were included in the network meta-analysis including 1953 patients randomly assigned to four JAK inhibitors-ruxolitinib, fedratinib, pacritinib, momelotinib-or control. In first-line therapy, momelotinib and fedratinib were associated with comparable efficacy to ruxolitinib, and with less toxicity on erythrocytes and platelets, respectively. Pacritinib was less effective on splenomegaly than ruxolitinib as a first-line treatment but seemed effective in second line, after ruxolitinib exposure. Fedratinib and ruxolitinib that are FDA approved in myelofibrosis have both confirmed being valuable option to treat splenomegaly and constitutional symptoms, and their slightly different tolerance-profiles can guide therapeutic choice for first-line treatment, according to patient profile. Momelotinib could be another option especially due to its positive effect on anemia.
Topics: Bridged-Ring Compounds; Humans; Janus Kinase Inhibitors; Nitriles; Primary Myelofibrosis; Pyrazoles; Pyrimidines; Pyrrolidines; Splenomegaly; Sulfonamides; Treatment Outcome
PubMed: 34315858
DOI: 10.1038/s41408-021-00526-z