Hodgkin’s-like disease of the thymus. Clinical,surgical and morphological correlations

Summary The histogenesis and relationship of so-called ‘granulomatous thymoma’ to Hodgkin’s disease is still a matter of controversy. Three of these lesions were selected from 43 thymomas and their clinico-pathological patterns are described. Two cases were diagnosed as Hodgkin’s disease of the mediastinum because of the absence of epithelial structures of thymic origin. In one case, together with the morphological aspects of Hodgkin’s disease, we noticed epithelial structures indicating a primary neoplastic lesion in the thymus. Accordingly we conclude that the term ‘Hodgkin’s disease of the thymus’ must be limited only to those lesions of the mediastinum in which structures of thymic origin are present. Other mediastinal Hodgkin’s lesions, even in the presence of clinical, radiological and surgical evidence of thymic origin but in which it is not possible to observe such thymic structures, must be classified as Hodgkin’s disease localized to the anterior mediastinum.     

Burning mouth syndrome in Parkinson’s disease: dopamine as cure or cause?

Burning mouth syndrome has been reported as being more common in Parkinson’s disease patients than the general population. While the pathophysiology is unclear, decreased dopamine levels and dopamine dysregulation are hypothesized to play a role. We report a patient with Parkinson’s disease who developed burning mouth syndrome with carbidopa/levodopa. Our patient had resolution of burning mouth symptoms when carbidopa/levodopa was replaced with a dopamine agonist. Based on our patient’s clinical course, in conjunction with earlier studies assessing the relationship between burning mouth syndrome and Parkinson’s disease, we discuss a potential role for dopamine in burning mouth syndrome in Parkinson’s disease.     

Small bowel imaging: CT enteroclysis or barium enteroclysis? Critically appraised topic

Barium enteroclysis has been traditionally used in the diagnosis of small bowel Crohn’s disease. Recently CT enteroclysis has been developed as an alternative imaging technique for small bowel Crohn’s disease. A search and critical appraisal of the literature was performed to determine which technique is better for diagnosis of Crohn’s disease. The best current evidence indicates that CT enteroclysis is a good test for the diagnosis of Crohn’s disease but barium enteroclysis may also be required in a small group of patients.     

Perianal fistulas in Crohn’s disease: MRI diagnosis and surgical planning

Crohn’s disease is a chronic, transmural inflammatory process of the gastrointestinal tract. It often affects the colon with the perianal area. The most common intestinal manifestations include external and/or internal fistulas and abscesses. Assessment of the activity of perianal fistulas in the course of Crohn’s disease seems to be an important factor influencing therapeutic approach. Fistula’s activity is evaluated by such methods as magnetic resonance imaging, anal ultrasound and examination under anaesthesia. Usefulness of imaging methods in the diagnosis of fistulas still remains to be defined. MRI is used to present a wide spectrum of perianal fistulazing Crohn’s disease. Additionally, it is an important instrument revealing location, extent and severity of inflammation. It is also very helpful to detect clinically silent sepsis related to small, local inflammation. The most common method used in MR imaging to assess topography of a fistula’s track, is Parks’ classification. Clinical indications to MRI may include follow-up studies of a diagnosed disease, classification of fistulas’ subtypes in the course of Crohn’s disease, determination of the extent of fistulas’ tracts and spread of an inflammatory process what can guide surgical procedures.     

Crohn’s disease clinical issues and treatment: what the radiologist needs to know and what the gastroenterologist wants to know

Crohn’s disease is an idiopathic chronic intestinal illness that requires specialized medical care for prompt disease diagnosis and appropriate management. Clinicians must accurately interpret and integrate findings from multitude of sources in order to achieve diagnostic certainty. Ileocolonoscopy remains the most relied modality, allowing for a direct mucosal visualization and biopsies for histologic assessments. Serologic markers currently serve an adjunctive role, often utilized in attempts to further subtype patients with indeterminate colitis. Radiologic imaging, such as computed tomography enterography can evaluate the far reaches of the small intestine, while also providing information about penetrating complications and extraintestinal disease manifestations. Treatment options and strategies continue to evolve with new biologic agents and ongoing testing of aggressive “top–down” approaches. In addition, identification of increased colorectal cancer risks in individuals with Crohn’s colitis has led to formal surveillance guidelines. The clinical diagnosis and management of Crohn’s disease continues to be an area of rapid change and exciting developments.     

Phosphorus-31 Two-Dimensional Chemical Shift Imaging in the Myocardium of Patients with Late Onset of Friedreich Ataxia

Purpose Friedreich ataxia (FRDA) is characterized by GAA expansions in the intron 1 of the frataxin gene correlating with disease onset and progression as well as cardiac affection. Accordingly, FRDA patients with early disease onset show a clear impairment of mitochondrial function in the myocardium. The purpose of this study was to investigate cardiac function and high-energy phosphate metabolism in FRDA patients with late disease onset. Procedures Using a 1.5 T magnetic resonance scanner, cardiac phosphorus-31 two-dimensional chemical shift imaging was performed in ten patients (seven male, three female) with a late onset of FRDA and in 35 healthy, male controls. Ejection faction (EF) and interventricular septum thickness (IST) were determined by echocardiography. Results The differences in left ventricular phosphocreatine (PCr) to β-adenosine triphosphate (β-ATP) ratios between both groups were not significant. FRDA patients had increased ISTs (10.8 ± 1.6 vs. 9.7 ± 0.9 mm; p = 0.048), which correlated significantly with the left ventricular PCr to β-ATP ratios (r = −0.644; p = 0.04), and decreased EFs (52.24 ± 7.72% vs. 64.09 ± 4.25%; p = 0.001) compared to normal controls. Conclusions In contrast to FRDA patients with early disease onset, our patients collective exhibited a normal, probably compensated cardiac mitochondrial function, whereby IST and EF were mildly altered.     

Renal involvement by Rosai–Dorfman disease: CT findings

Rosai–Dorfman disease is a rare disease characterized histologically by proliferation of histiocytes and has clinical features suggestive of a lymphomalike disease. Lymph nodes and extranodal sites might be involved, but renal involvement is rare. We present computed tomographic findings in three cases of renal involvement by Rosai–Dorfman disease. Two cases showed renal hilar masses and one case showed subcapsular hypodense infiltration. Renal involvement by Rosai–Dorfman disease has a characteristic appearance and should be included in the differential diagnosis of renal hilar masses or subcapsular hypodense infiltration. Received: 13 March 2001/Accepted: 18 April 2001     

Feasibility of 2–deoxy–2–[18F]fluoro–D–glucose– A85380–PET for imaging of human cardiac nicotinic acetylcholine receptors in vivo

Summary Nicotinic acetylcholine receptors mediate the parasympathetic autonomic control of cardiac function. Aim of this study was the assessment of cardiac nicotinic acetylcholine receptor distribution with a novel (α₄β₂) nicotinic acetylcholine receptor PET ligand (2–deoxy–2– [¹⁸F]fluoro–D–glucose–A85380) in humans. Five healthy volunteers without cardiac disease and six patients with either Parkinson's disease or multiple system atrophy without additional overt cardiac disease were evaluated with 2–deoxy–2–[¹⁸F]fluoro–D–glucose–A85380 PET–imaging to assess the cardiac parasympathetic innervation and the putative impact of both disorders. 2–deoxy–2– [¹⁸F]fluoro–D–glucose–A85380 whole body PET–scans were performed on a Siemens PET/CT biograph^TM 75.4 min±6.7 after i.v. injection of 371.2±58.1 MBq. Average count rate density of left ventricle ROI's and a standard ROI in the right lung were measured within three consecutive slices of 10.0 mm thickness. Heart–to–lung ratios were calculated in each volunteer and patient. Tracer uptake in the left ventricle could be measured in all of the five volunteers and the six patients. Heart–to–lung ratios in the volunteer group were not different from patients suffering from Parkinson's disease or MSA (3.2 ± 0.5 vs 3.2 ± 0.8 and 2.96±0.7, mean ± SD), respectively. Human cardiac nicotinic acetylcholine receptors can be visualized and measured by 2–deoxy–2– [¹⁸F]fluoro–D–glucose–A85380 PET scans both in cardiac–healthy subjects and patients suffering from Parkinson's disease or multiple system atrophy. The heart– as well as the lung–tracer uptake was almost constant throughout all subjects leading to a good targetto– background ratio. These first results suggest no impact of either PD or MSA on cardiac nicotinic acetylcholine receptors. An erratum to this article is available at .     

<Superscript>18</Superscript>F-FDG positron emission tomography: potential utility in the assessment of Crohn’s disease

Computed Tomography Enterography (CTE) and Magnetic Resonance Enterography (MRE) are currently the dominant imaging tests used in the assessment of patients with Crohn’s disease. More recently, the possibility of utilizing F-18 fluorodeoxyglucose (18F-FDG) Positron Emission Tomography (PET) or PET/CT has been explored in several preliminary studies. 18F-FDG PET appears to enable reliable detection of moderate to severe inflammation in bowel segments involved by Crohn’s disease. Perhaps more importantly, 18F-FDG PET has the potential to provide a noninvasive, quantitative measure of inflammation that dynamically reflects changes in Crohn’s disease activity. If 18F-FDG PET proves useful in monitoring responses to medical therapy within a few days of therapy initiation, an important new role for imaging in the management of patients with Crohn’s disease could emerge.     

Does the urinary excretion of α1-microglobulin and albumin predict clinical disease activity in ulcerative colitis?

Introduction  There remains some difficulty in determining disease activity during the development of inflammatory bowel disease (IBD). The excretion levels of some inflammatory response molecules increase as a result of the onset of this disease. We studied urinary alfa-1-microglobulin (α1-MG) and albumin levels in patients with active and inactive ulcerative colitis (UC) and investigated whether we could use these parameters as an activity index. Methods  The study was carried out at Gazi University Faculty of Medicine, Nephrology and Gastroenterology Departments, between December 2003 and March 2006. In total, 35 patients (male/female: 16/19, mean age: 38.3±2.4 years) and 13 healthy controls (male/female: 6/7, mean age: 35.8±2.8 years) were enrolled in the study. Nineteen patients had symptoms of active disease and the remaining 16 patients had inactive disease. Results  There was a significant difference in serum C-reactive protein (CRP), urinary albumin excretion, and α1-MG excretion levels between patients and controls. Patients with active disease had significantly higher serum CRP and α1-MG levels than those with inactive disease and controls. Patients with active disease had higher microalbuminuria levels than inactive patients, but this difference was not statistically significant. Urinary albumin and α1-MG excretion did not correlate with serum CRP levels. Conclusion  The present study suggests that, as with CRP, urinary levels of albumin and α1-MG increase during the active period of UC. During the inactive period, concentrations of these parameters are comparable to controls. The measurement of α1-MG and/or microalbuminuria could provide information on disease severity and response to treatment.     

Determination of serum angiotensin-converting enzyme in sarcoidosis

Summary Serum angiotensin-converting enzyme activity was measured in 72 patients with sarcoidosis and in 50 normal controls by a radiochemical assay. SACE levels were examined with respect to the ‘activity’ of the disease, based on clinical, radiographic and physiological assessment. SACE activity in 34 patients with clinical sarcoidosis (147±44.3 nmol/min/ml) was significantly high (p<0.001) when compared to that of 38 patients who had recovered from sarcoidosis (113.9±26.4 nmol/min/ml) and 50 normal subjects (97.8±21 nmol/min/ml). SACE levels were significantly different (p<0.01) between 15 subjects with ‘active’ disease (173.9±51.9 nmol/min/ml) and those with ‘inactive’ disease (126.1±26.3 nmol/min/ml). It is concluded that there is a strict correlation between SACE levels and ‘activity’ of sarcoidosis if multiple criteria (clinical, radiographic and physiological) are employed.     

Prognostic factors in patients with aggressive non-Hodgkin’s lymphoma without complete response to first-line therapy

This study was conducted to retrospectively identify the prognostic factors that specifically predict survival rates of patients with aggressive non-Hodgkin’s lymphoma who did not achieve a complete response (CR) to first-line therapy. Prognostic factors in terms of survival were analyzed in 76 adult patients with non-Hodgkin’s lymphoma who had failed to achieve CR to first-line chemotherapy (CT) regimens administered at Istanbul University, Institute of Oncology, between February 1989 and October 1998. A total of 41 patients were female, and median age was 60 y (range, 18–87 y). Twenty-seven patients (35%) had primary refractory disease (stable disease + progressive disease). A partial response (PR) was demonstrated in 49 (65%). In all, 92% had been administered anthracycline on the basis of computed tomography findings. Of 27 patients with primary refractory disease, 20 died because of initial CT toxicity or disease progression. A total of 10 patients with primary refractory disease underwent second-line CT. CR was observed in only 1 of those patients. Of the 49 patients who had a PR to first-line therapy, 31 died because of disease progression. Of those patients, 14 underwent second-line CT. Four patients were observed to have a CR. Median overall survival (OS) in all patients was established at 15 mo (range, 11–19 mo), and 5-y OS was 25%. On the other hand, median OS in patients with primary refractory disease was 7.6 mo (range, 5.7–9.4 mo) and was observed to be 17.8 mo (range, 9.4–26.1 mo) in patients with a PR. The difference in survival rates between patients with primary refractory disease and those with a PR was significant (P=.005). Although median OS was 18.1 mo (range, 8.4–27.8 mo) in patients with intermediategrade histology, it was 6.1 mo (range, 1–11.7 mo) in patients with high-grade histology (P=.001). As a result of univariate analysis, significant prognostic factors associated with OS included histologic grade (intermediate/high) (P=.001), response to initial therapy (primary refractory disease/PR) (P=.005), performance status (0–2/2–4) (P=.024), and International Prognostic Index risk groups (low/low intermediate/intermediate-high/high risk) (P=.004). Multivariate analysis revealed that independent prognostic parameters associated with OS included response to initial therapy (P=.009) and histologic grade (P=.001). Although prognosis is rather poor in patients with high histologic grade and primary refractory disease, patients with a PR have a slightly better prognosis.     

Retrospective evaluation of a paediatric intensivist-led flexible bronchoscopy service

Objective To demonstrate the diagnostic yield, therapeutic role and safety of flexible bronchoscopy via an intensivist-led service in critically ill children.Design Retrospective chart review.Setting Regional paediatric intensive care unit.Measurements and results One hundred forty-eight flexible bronchoscopies were performed by two intensivists on 134 patients (median age 16.5 months) over a 2.5-year period. Eighty-eight percent of patients required mechanical ventilation, and 22% were receiving inotropes. Case mix included general (n = 77), cardiac surgery (n = 18), cardiology (n = 13), ear-nose-and-throat surgery (n = 17), oncology (n = 8) and renal (n = 1). The indication for bronchoscopy was defined a priori according to one of four categories: suspected upper airway disease (n = 32); lower airway disease (n = 70); investigation of pulmonary disease (n = 25); and extubation failure (n = 21). Bronchoscopy was generally performed soon after PICU admission, at a median time of 1.5 days for the former three categories, and 4 days for extubation failure group. A positive yield from bronchoscopy (diagnosis that explained the clinical condition or influenced patient management) was present in 113 of 148 (76%) procedures, varying within groups from 44% (pulmonary disease) to 90% (extubation failure).Ten percent of patients developed a fall in oxygen saturations > 20% during the procedure and 17% required a bolus of at least 10 ml/kg of 0.9% saline for hypotension.Conclusions Critically ill patients with respiratory problems may benefit from a PICU-led bronchoscopy service as the yield for positive bronchoscopic finding is high, particularly for upper airway problems or extubation failure.     

Role of echocardiography in the assessment and management of adult congenital heart disease in pregnancy

Congenital heart disease represent a large proportion of heart disease in pregnancy. With the exception of patients with Eisenmenger’s syndrome, pulmonary vascular obstructive disease, and Marfan’s syndrome with aortopathy, maternal death during pregnancy is rare in women with CHD but morbidity occurs such as heart failure, arrhythmias, and stroke. Echocardiography represents a milestone in diagnosis, understanding of pathophysiology, assessment of disease severity and patient monitoring in pregnant women with unoperated and post-operative congenital heart disease.     

Feasibility of 2–deoxy–2–[18F]fluoro–D–glucose– A85380–PET for imaging of human cardiac nicotinic acetylcholine receptors in vivo

Summary  Nicotinic acetylcholine receptors mediate the parasympathetic autonomic control of cardiac function. Aim of this study was the assessment of cardiac nicotinic acetylcholine receptor distribution with a novel (α₄β₂) nicotinic acetylcholine receptor PET ligand (2–deoxy–2– [¹⁸F]fluoro–D–glucose–A85380) in humans. Five healthy volunteers without cardiac disease and six patients with either Parkinson's disease or multiple system atrophy without additional overt cardiac disease were evaluated with 2–deoxy–2–[¹⁸F]fluoro–D–glucose–A85380 PET–imaging to assess the cardiac parasympathetic innervation and the putative impact of both disorders. 2–deoxy–2– [¹⁸F]fluoro–D–glucose–A85380 whole body PET–scans were performed on a Siemens PET/CT biograph^TM 75.4 min±6.7 after i.v. injection of 371.2±58.1 MBq. Average count rate density of left ventricle ROI's and a standard ROI in the right lung were measured within three consecutive slices of 10.0 mm thickness. Heart–to–lung ratios were calculated in each volunteer and patient. Tracer uptake in the left ventricle could be measured in all of the five volunteers and the six patients. Heart–to–lung ratios in the volunteer group were not different from patients suffering from Parkinson's disease or MSA (3.2 ± 0.5 vs 3.2 ± 0.8 and 2.96±0.7, mean ± SD), respectively. Human cardiac nicotinic acetylcholine receptors can be visualized and measured by 2–deoxy–2– [¹⁸F]fluoro–D–glucose–A85380 PET scans both in cardiac–healthy subjects and patients suffering from Parkinson's disease or multiple system atrophy. The heart– as well as the lung–tracer uptake was almost constant throughout all subjects leading to a good target–to–background ratio. These first results suggest no impact of either PD or MSA on cardiac nicotinic acetylcholine receptors. The Article “Feasibility of 2-deoxy-2-[¹⁸F]fluoro-D-glucose-A85380-PET for imaging of human cardiac nicotinic acetylcholine receptors in vivo” by J. Bucerius et al. (the online version can be found at has been published in issue 95 (2006):105–109. Unfortunately a wrong notation for the tracer was given. Instead of 2-deoxy-2-[¹⁸F]fluoro-D-glucose-A85380 it should be 2-[¹⁸F]-A85380. The publisher apologies for any inconvenience caused by this mistake.     

Epstein-Barr virus and hodgkin’s disease

Summary Seroepidemiological and molecular biological studies have established an association of Hodgkin’s disease with Epstein-Barr virus. Recently, Epstein-Barr virus genomes and gene products have been detected in the neoplastic cells of approximately 50% of cases, most notably the latent membrane protein, which has transforming potential. However, Epstein-Barr virus was not restricted to neoplastic cells. In situ hybridization, employing probes for the small Epstein-Barr virus-encoded nuclear RNAs EBER 1 and −2, helped to precisely characterize phenotype and distribution of all latently Epstein-Barr virus-infected cells, indicating the presence of usually small numbers of Epstein-Barr virus-infected, but latent membrane protein-negative, non-malignant B-cells of polyclonal origin in lymph nodes from Hodgkin’s disease patients and normal controls. In contrast, the neoplastic cells and the Epstein-Barr virus genomes expressing latent membrane protein in these cells appear to be monoclonal in nature, which points to specific immunological deficiencies in Hodgkin’s disease patients and suggests that Epstein-Barr virus may contribute to the etiology of a significant proportion of Hodgkin’s disease cases.     

Potential of Dual Time Point FDG-PET Imaging in Differentiating Malignant from Benign Pleural Disease

Aim  The aim of this study was to assess the utility of dual time point ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET) imaging in differentiating benign from malignant pleural disease. Methods  Fifty-five consecutive patients of suspected malignant pleural mesothelioma (MPM) and recurrence of MPM who were referred for the evaluation underwent two sequential ¹⁸F-FDG-PET scans (dual time point imaging). The average percent change in the maximum standardized uptake values (Δ%SUVmax) of the lesion/lesions between time point 1 (SUV_max1) and time point 2 (SUV_max2) was calculated. All PET results were correlated with the histopathological or cytopathology results. Patients were divided into three principal groups (A = newly diagnosed MPM, B = recurrent MPM, and C = benign pleural disease). The parameters of ¹⁸F-FDG uptake (SUV_max values and its changes over time) were compared among groups. Results  Among the 55 patients who had undergone dual time point ¹⁸F-FDG-PET studies, 44 were diagnosed with MPM (28 newly diagnosed and 16 had recurrence). The PET studies demonstrated 229 malignant pleural lesions in these patients. The remaining 11 patients were proven to have benign pleural disease. The mean ± SD of the SUV_max1, SUV_max2, and the Δ%SUV_max of the all lesions of each patient in groups A, B, and C were 5.0 ± 2.2%, 5.8 ± 2.8%, and 12.8 ± 8.4%; 4.6 ± 1.7%, 5.3 ± 2.0%, 13.8 ± 9.2%; and 1.6 ± 0.4%, 1.4 ± 0.3%, and–9.6 ± 19.1%, respectively. The mean ± SD of the SUV_max1, SUV_max2, and Δ%SUV_max in patients with both newly diagnosed and recurrent MPM were significantly higher than those of benign pleural disease group (p < 0.0001). For each patient, the most intense (hottest) lesion’s SUV_max1, SUV_max2, and Δ%SUV_max were also compared among the aforementioned groups, and these results again confirmed that MPM lesions had significantly higher values than those of benign pleural lesions (p < 0.0001). Conclusions  There is an increasing uptake of ¹⁸F-FDG over time in pleural malignancies, whereas the uptake in benign pleural disease generally stays stable or decreases over time. Therefore, dual time point imaging appears to be an effective approach in differentiating benign from malignant pleural disease, which increases the sensitivity and is also helpful in guiding the biopsy site for a successful diagnosis.     

A Study of the Caeruloplasmin Concentrations found in 75 Patients with Wilson's disease, their Kinships and Various Control Groups

We have studied the concentration of the blue copper proteincaeruloplasmin in the serum of 195 young, normal adults, 147patients with neurological diseases and 78 patients with subacuteor chronic liver disease. These have served as controls for75 patients with Wilson's disease before treatment was startedand during follow up for periods extending up to 20 years. Wehave also studied 444 members of the kinships. Caeruloplasmin has been estimated by an enzyme assay using dimethylpphenylenediamine as substrate and, when necessary, we havechecked the values so obtained by a new immunoenzymatic methodand also by determining serum copper. The mean caeruloplasmin concentration in 83 normal males was333.3 mg/l (S.D. 60·7). In 112 females it was 410·1mg/l (S.D. 130·2). These 112 females were shown to comprisetwo populations, the larger (n 82) had a mean of 365·6mg/l (S.D. 92·8) and the smaller a mean of 606·6mg/l (S.D. 157·5). The former figure is taken as thenormal. The mean value for 75 patients with Wilson's disease was 63·3mg/l (S.D. 87·6) before treatment; after treatment itfell to 45·0 mg/l (S.D. 79·8). However in 11 ofthese patients the mean caeruloplasmin concentration rose, aftertreatment, from 108·5 mg/l (S.D. 27·7) to 168·7mg/l (S.D. 33·6). The mean values for the hepatic and neurological control casesclosely approximated to the mean values for the sex matchednormals. However both these groups showed a wide range of variationwith many patients falling outside the normal 95 per cent confidencelimits. Low caeruloplasmin values in patients with either hepaticor neurological disease may lead to considerable diagnosticconfusion. The mean caeruloplasmin concentration for the obligate heterozygoteswas significantly depressed in bath males and females but only36 out of 160 fell below the normal 95 per cent confidence limit.The percentage of detectable heterozygotes fell, as did thecalculated gene frequency, in more distant relatives. When there was a marked and unexpected discrepancy between theserum caeruloplasmin concentration as estimated by the enzymaticassay and the serum copper concentration the caeruloplasminvalue was checked by the immunoenzymatic method. In patientswith liver disease and in those with treated Wilson's diseasethe immunoenzymatic method was found to be in good agreementwith the serum copper concentration. This suggests that thereis, in some patients, an inhibitor present which interfereswith the enzymatic assay. The finding of a low caeruloplasminlevel in the serum of a patient with undiagnosed hepatic orneurological disease by an enzymatic method cannot be takenas evidence of absence of this protein unless it is confirmedby an immunological technique.     

Clinical significance of hepatocyte growth factor, platelet-derived growth factor-AB, and transforming growth factor-α in bone marrow and peripheral blood of patients with multiple myeloma

Angiogenesis is a process that plays an important role in the growth and progression of cancer; growing evidence suggests that neovascularization is important in hematologic malignancies. Increased angiogenic potential has been identified in multiple myeloma (MM). In this study, investigators simultaneously measured the levels of hepatocyte growth factor (HGF), platelet-derived growth factor-AB (PDGF-AB), and transforming growth factor-alpha (TGF-/ga) through enzyme-linked immunosorbent assay in the bone marrow (BM) and peripheral blood (PB) of 30 patients with MM and 10 healthy controls. Differences in HGF values in BM sera were significant (P=.001) between patients and controls. In detailed analyses of HGF, PDGF-AB, and TGF-α, according to disease stage, a significant correlation was found between disease stage and BM HGF (P=.047), BM TGF-α (P=.021), and PB PDGF-AB (P=.006), respectively. When correlations between all other parameters were analyzed, significance was noted between PB TGF-α and lactate dehydrogenase (P=.02), PB TGF-α and PB HGF (P=.002), BM TGF-α and CD38 (P=.046), BM TGF-α and BM HGF (P=.000), BM TGF-α and BM PDGF-AB (P=.048), BM HGF and PB HGF (P=.044), and BM PDGF-AB and PB PDGF-AB (P=.000). BM HGF levels had a significant effect on overall survival, with disease severity assessed in terms of disease stage (P=.0018, log-rank test). These data show that in patients with MM, high levels of BM HGF, BM TGF-α, and PB PDGF-AB were associated with advanced disease stage; in addition, HGF played a significant role in disease processing and was related to disease severity. These findings have also led to the concept of a symbiotic relationship between the growth of myeloma cells and HGF, TGF-α, and PDGF-AB in BM.