Event free survival at 24 months is a strong surrogate prognostic endpoint of peripheral T cell lymphoma

Event free survival at 24 months (EFS24) has been described as a powerful predictor for outcome in several subtypes of B cell lymphoma. However, it was limitedly described in T cell lymphoma. We explored the implication of EFS24 as a predictor marker for peripheral T cell lymphoma (PTCL). We reviewed 293 systemic PTCL patients at 13 nationwide major university hospitals in Thailand from 2007 to 2014. The median event free survival (EFS) and overall survival (OS) of PTCL patients in our cohort was 16.3 and 27.7 months with corresponding 2‐year EFS and 2‐year OS of 45.8% and 51.9%, respectively. A total of 118 patients achieved EFS24 (no events during the first 24 mo). Patients who achieved EFS24 had better OS than patients who did not (2‐y OS 92% vs 18.8%; HR, 0.1; P < .001). The standardized mortality ratio of patients achieving EFS24 was 18.7 (95% CI, 14.6‐22.8). Multivariable analysis demonstrated performance status, histologic subtype, remission status, and EFS24 achievement as independent predictors for OS. Our study affirmed the value of EFS24 as a powerful prognostic factor for PTCL. Further validation in prospective study setting is warranted.     

Mediastinal small cell carcinoma with liver and bone marrow metastasis,mimicking lymphoma

Primary mediastinal neuroendocrine tumors are a rare malignancy that accounts for 10% of all mediastinal tumors. The case presented here involves a 52-yearold man who had been suffering for 3 mo from chronic cough, anorexia and substantial weight loss, as well as 2 wk of jaundice prior to his admission. A computed tomography scan showed a 4.3 cm × 6.6 cm mediastinal mass with multiple liver nodules scattered along both hepatic lobes. Endoscopic ultrasound showed a large heterogeneous hypoechoic mass at the mediastinum with multiple target-like nodules in the liver. Fine-needle aspiration specimens revealed numerous, small, round cells with hyperchromatic nuclei, scarce cytoplasm, and frequent mitotic features. Immunohistochemical study revealed positive results for AE1/AE3, CD56 and chromogranin A, with negative findings for synaptophysin, CK20, vimentin, CK8/18 and CD45. The patient was subsequently diagnosed with a poorly differentiated neuroendocrine carcinoma, small cell type. A bone marrow biopsy also revealed extensive involvement by the carcinoma.     

Hemodynamic maladjustment and disease progression in nephrosis with FSGS

Idiopathic nephrotic syndrome (NS) associated with focal segmental glomerulosclerosis (FSGS) and severe renal function impairment is usually refractory to the conventional treatment and progresses to end-stage renal disease. Herein, we reported 10 patients with NS-FSGS who had initially had CCr 34 +/- 12 mL/min/1.73 m2 (normal 120 mL/min/1.73 m2), FE Mg 7.8 +/- 2.6% (normal 2.2%), 24-h urinary protein 3.1 g (normal <200 mg) and been followed up for over 10 years. The initial intrarenal hemodynamic study revealed a marked elevation of efferent arteriolar resistance (RE 17289 +/- 8636 dyne x s x cm(-5); normal 3000 dyne x s x cm(-5)), intraglomerular hypertension (PG 57 +/- 1 mm Hg; normal 52 mm Hg), hyperfiltration (FF 0.24; normal 0.2), marked reductions in GFR 35 +/- 17 mL/min/1.73 m2, renal plasma flow (RPF 159 +/- 61 mL/min/1.73 m2; normal 600 mL/min/1.73 m2) and peritubular capillary flow (PTCF 123 +/- 57 mL/min/1.73 m2; normal 480 mL/min/1.73 m2). Such a hemodynamic alteration indicated a hemodynamic maladjustment with a preferential constriction at RE. Treatment consists of multidrugs, namely angiotensin converting enzyme inhibitor, calcium channel blocker, antiplatelet and anticoagulant, with or without angiotensin II receptor antagonist. Following the treatment, correction of hemodynamic maladjustment has been achieved which is characterized by reductions in RE 6046 +/- 2191 dyne x s x cm(-5), PG 52 +/- mm Hg, FF 0.19 +/- 0.1 and increments in RPF 341 +/- 118 mL/min/1.73 m2, PTCF 280 +/- 106 mL/min/1.73 m2 and GFR 64 +/- 17 mL/min/1.73 m2. Coinciding with hemodynamic improvement, there has been a steadily increased creatinine clearance and improvement in FE Mg 4.3 +/- 2.6% and suppression of proteinuria 0.29 +/- 0.4 g/24 h after the period of follow-up of greater than 10 years.     

Relationships between OPG,RANKL, bone metabolism,and bone mineral density in biliary atresia

Purpose  Osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) have been implicated in osteoclastogenesis. However, the relationship between the OPG–RANKL system and bone status in biliary atresia (BA) has not, as yet, been clarified. Thus, the aim of this study has been to evaluate the relationship between the OPG–RANKL system and bone mineral metabolism in patients with BA. Methods  Fifty patients with BA and 13 healthy controls were investigated. The mean age of BA patients and controls was 7.3 ± 0.6 and 8.0 ± 1.1 years, respectively. Serum levels of OPG, RANKL, osteocalcin, and C-terminal telopeptide of type I collagen (CTX) were measured by sandwich enzyme-linked immunosorbent assay. Bone mineral density (BMD) of the lumbar spine was determined by dual energy X-ray absorptiometry. Results  Biliary atresia patients had significantly elevated serum OPG levels compared with controls (4.0 ± 0.3 vs. 3.0 ± 0.3 pmol/L, P = 0.02) and serum OPG levels in BA patients with jaundice were higher than in those without jaundice (4.6 ± 0.4 vs. 3.6 ± 0.4 pmol/L, P = 0.04). Likewise, serum RANKL levels were significantly higher in BA patients than in controls (2.9 ± 0.2 vs. 1.2 ± 0.7 pmol/L, P = 0.001). In addition, serum RANKL levels were increased in BA patients with jaundice compared to those without jaundice, but this difference was not statistically significant (3.2 ± 0.3 vs. 2.7 ± 0.2 pmol/L, P = 0.2). The serum osteocalcin levels in BA patients were not significantly different from those in the healthy controls, whereas the serum CTX levels were elevated in BA patients compared with the controls (0.4 ± 0.1 vs. 0.2 ± 0.1 ng/mL, P = 0.02). Furthermore, BMD of BA children with jaundice was significantly lower than that of BA children without jaundice (P = 0.0005). BMD of BA patients was inversely correlated with serum levels of OPG (r = −0.452, P < 0.001). Conclusion  Elevated serum OPG levels are associated with reduced BMD and the outcome of BA. The increase of serum OPG in BA patients with severe disease could reflect a compensatory response to bone loss. Presented at the 30th American Society for Bone and Mineral Research (ASBMR) annual meeting, Montreal, Quebec, Canada, 12–16 September 2008.     

Extra-pulmonary tuberculosis at a regional hospital in Thailand

The purpose of this study was to analyze the cases of extra-pulmonary tuberculosis (EPTB) at Maharat Nakhon Ratchasima Hospital, a tertiary care regional hospital in Northeast Thailand. There were 398 cases of EPTB (46.9%) and 450 cases of pulmonary tuberculosis (PTB) (53.1%). The mean age of EPTB patients (47.58 years) was lower than that of PTB patients (51.6 years) (p < 0.01). Human Immunodeficiency Virus (HIV) seropositivity was found in 50 cases of EPTB (12.6%) and 55 cases of PTB (12.2%) which was not significantly different. The common sites of extra-pulmonary involvement were the lymph nodes (29.7%), followed by the pleura (27.4%), the bones and spine (25.1%), the meninges and brain (4.5%), the pericardium (3.5%) and the gastrointestinal tract (3.0%). Disseminated TB occurred in only 8 cases (2.0%). HIV seropositivity rates were more common in disseminated TB (OR 41.51, 95% CI 4.98-34.5), TB of the meninges and brain (OR 4.47, 95% CI 1.57-12.6) and TB of the lymph nodes (OR 3.49, 95% CI 1.86-6.54) and were less common in TB of the bones and spine (OR 0.05, 95% CI 0.01-0.37) and TB of the pleura (OR 0.24, 95%CI 0.09-0.63).     

Extranodal NK/T-cell lymphoma, nasal type, includes cases of natural killer cell and αβ, γδ, and αβ/γδ T-cell origin: a comprehensive clinicopathologic and phenotypic study

Extranodal NK/T-cell lymphoma (ENKTL), nasal type, may be of NK or T-cell origin; however, the proportion of T-ENKTLs and whether they are of αβ or γδ type remains uncertain. To elucidate the cell of origin and detailed phenotype of ENKTL and assess any clinicopathologic associations, 67 cases of ENKTL from Thailand were investigated, together with 5 γδ enteropathy-associated T-cell lymphomas (EATLs) for comparison. In all, 70% of the ENKTL were T-cell receptor (TCR) β,γ and, in cases tested, δ negative (presumptive NK origin); 5% were TCR γδ, 3% were TCR αβ, 1% were TCR αβ/γδ, and 21% were indeterminate. Out of 17 presumptive NK-ENKTLs tested, 3 had clonal TCR rearrangements. All cases were EBV and TIA-1; >85% were positive for CD3, CD2, granzyme B, pSTAT3, and Lsk/MATK; and all were CD16. Presumptive NK-ENKTLs had significantly more frequent CD56 (83% vs. 33%) and CXCL13 (59% vs. 0%) but less frequent PD-1 (0% vs. 40%) compared with T-ENKTLs. Of the NK-ENKTLs, 38% were Oct-2 compared with 0% of T-ENKTLs, and 54% were IRF4/MUM1 compared with 20% of T-ENKTLs. Only αβ T-ENKTLs were CD5. Intestinal ENKTLs were EBV and had significantly more frequent CD30, pSTAT3, and IRF4/MUM1 expression but less frequent CD16 compared with γδ EATL. Significant adverse prognostic indicators included a primary non-upper aerodigestive tract site, high stage, bone marrow involvement, International Prognostic Index ≥2, lack of radiotherapy, Ki67 >40%, and CD25 expression. The upper aerodigestive tract ENKTLs of T-cell origin compared with those of presumptive NK origin showed a trend for better survival. Thus, at least 11% of evaluable ENKTLs are of T-cell origin. Although T-ENKTLs have phenotypic and some possible clinical differences, they share many similarities with ENKTLs that lack TCR expression and are distinct from intestinal γδ EATL.