The objective of this study was to investigate whether metabolic tumor volume (MTV) by positron emission tomography (PET) can be a potential prognostic tool when compared with Ann Arbor stage, in stages II and III nodal diffuse large B cell lymphoma (DLBCL). We evaluated 169 patients with nodal stages II and III DLBCL who underwent measurements with PET prior to rituximab combined with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP). Cutoff point of MTV was measured using the receiver operating characteristic (ROC) curve. During a median period of 36 months, stage II was 59.2% and III was 40.8%. Using the ROC curve, the MTV of 220 cm³ was the cutoff value. The low MTV group (<220 cm³) had longer progression-free survival (PFS) and overall survival (OS), compared with the high MTV group (≥220 cm³) (p < 0.001, p < 0.001). Stage II patients had longer survival than those in stage III (PFS, p = 0.011; OS, p = 0.001). The high MTV group had lower PFS and OS patterns, regardless of stage, compared with the low MTV group (p < 0.001, p < 0.001). Multivariate analysis revealed an association of the high MTV group with lower PFS and OS (PFS, hazard ratio (HR) = 5.300, p < 0.001; OS, HR = 7.009, p < 0.001), but not stage III (PFS, p = 0.187; OS, p = 0.054). Assessment of MTV by PET had more potential predictive power than Ann Arbor stage in the patients that received R-CHOP.

Recent studies have shown that metabolic tumor volume (MTV) by positron emission tomography/computed tomography (PET/CT) is an important prognostic parameter in patients with non‐Hodgkin's lymphoma. However, it is unknown whether doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) alone in early stage Hodgkin's lymphoma would lead to similar disease control as combined modality therapy (CMT) using MTV by PET/CT. One hundred and twenty‐seven patients with early stage Hodgkin's lymphoma who underwent PET/CT at diagnosis were enrolled. The MTV was delineated on PET/CT by the area ≥SUV_max, 2.5 (standardized uptake value [SUV]). Sixty‐six patients received six cycles of ABVD only. The other 61 patients received CMT (involved‐field radiotherapy after 4–6 cycles of ABVD). The calculated MTV cut‐off value was 198 cm³. Clinical outcomes were compared according to several prognostic factors (i.e. age ≥50 years, male, performance status ≥2, stage II, B symptoms, ≥4 involved sites, extranodal site, large mediastinal mass, CMT, elevated erythrocyte sedimentation rate and high MTV). Older age (progression‐free survival [PFS], P = 0.003; overall survival [OS], P = 0.007), B symptoms (PFS, P = 0.006; OS, P = 0.036) and high MTV (PFS, P = 0.008; OS, P = 0.007) were significant independent prognostic factors. Survival of two high MTV groups treated with ABVD only and CMT were lower than the low MTV groups (PFS, P < 0.012; OS, P < 0.045). ABVD alone was sufficient to control disease in those with low MTV status. However, survival was poor, even if the CMT was assigned a high MTV status. The MTV would be helpful for deciding the therapeutic modality in patients with early stage Hodgkin's lymphoma.

Jang JH, et al. J Korean Med Sci. 2016 Feb;31(2):214-221. https://doi.org/10.3346/jkms.2016.31.2.214

The primary cause of death among chronic diseases worldwide is ischemic cardiovascular diseases, such as stroke and myocardial infarction. Recent evidence indicates that adult stem cell therapies involving cardiovascular regeneration represent promising strategies to treat cardiovascular diseases. Owing to their immunomodulatory properties and vascular repair capabilities, mesenchymal stem cells (MSCs) are strong candidate therapeutic stem cells for use in cardiovascular regeneration. However, major limitations must be overcome, including their very low survival rate in ischemic lesion. Various attempts have been made to improve the poor survival and longevity of engrafted MSCs. In order to develop novel therapeutic strategies, it is necessary to first identify stem cell modulators for intracellular signal triggering or niche activation. One promising therapeutic strategy is the priming of therapeutic MSCs with stem cell modulators before transplantation. Another is a tissue engineering-based therapeutic strategy involving a cell scaffold, a cell-protein-scaffold architecture made of biomaterials such as ECM or hydrogel, and cell patch- and 3D printing-based tissue engineering. This review focuses on the current clinical applications of MSCs for treating cardiovascular diseases and highlights several therapeutic strategies for promoting the therapeutic efficacy of MSCs in vitro or in vivo from cell priming to tissue engineering strategies, for use in cardiovascular regeneration.

Background: Rituximab has dramatic impact on outcome of patients with diffuse large B-cell lymphoma (DLBCL), especially nongerminal center (non-GC) type. A low absolute lymphocyte count (ALC) before rituximab, cyclophosphamide, vincristine, adriamycin, and prednisone (R-CHOP) therapy as a surrogate marker of immune status is associated with poor clinical outcome in DLBCL. Therefore, we hypothesized that low ALC before R-CHOP would have effect on the survival in non-GC type. Patients and methods: One hundred and thirty-six DLBCL patients who were treated with R-CHOP from 2003 to 2007 were analyzed in the present study. Results: ALC ≥1.0 × 10⁹/l predicted a longer 3-year progression-free survival (PFS) and 3-year overall survival (OS) versus ALC <1.0 × 10⁹/l (82.6% versus 60.0%, P = 0.005 and 87.2% versus 62.0%, P < 0.001, respectively). Non-GC type had similar PFS and OS to germinal center type (68.2% versus 80.0%, P = 0.074 and 72.7% versus 82.9%, P = 0.111, respectively). However, considering clinical influence of the ALC according to immunophenotype, low ALC in non-GC type DLBCL was associated with lower PFS and OS compared with others (PFS, P = 0.002; OS, P < 0.001). Multivariate analysis revealed that low ALC in non-GC type had lower PFS [hazard ratio (HR) = 3.324, P = 0.001] and OS (HR = 4.318, P < 0.001), independent of international prognostic index. Conclusion: A low ALC in non-GC type DLBCL counteracted the beneficial effect of rituximab on survival.

Primary gastrointestinal (PGI) diffuse large B cell lymphoma (DLBCL) is a relatively common disease. Recent studies indicate that measurement of maximum standardized uptake value (SUV_max) on pretreatment for ¹⁸F‐fluorodeoxyglucose PET is an important prognostic factor in PGI DLBCL. However, there is still an association between initial tumor burden and prognosis. Thus, in the present study, we investigated whether tumor volume by PET could have a potential prognostic value to predict the outcome. From 2006 to 2009, 165 Stage I E/II E PGI DLBCL patients were enrolled in the study. One hundred and five patients received cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (R‐CHOP) only, whereas 60 patients underwent surgery plus R‐CHOP. Metabolic tumor volume (MTV) was defined initial tumor burden as target GI lesion above SUV, 2.5 by PET as a contouring border. Over a median follow‐up period of 36.6 months, receiver operating characteristic (ROC) analysis indicated that the best cut‐off values for MTV and SUV_max were 160.1 cm³ and 12.0, respectively. The estimated area under the ROC curve was higher for MTV than SUV_max. Thus, MTV was a better predictor for survival than SUV_max. In patients with a low MTV (160.1 cm³), survival was longer in those who underwent surgery plus R‐CHOP than in those treated with R‐CHOP alone (P < 0.001 for PFS; P < 0.001 for OS). Multivariate analysis revealed that high MTV is an independent factor for predicting survival. Even in the era of rituximab, treatment of PGI DLBCL is not easy in patients with a high MTV. (Cancer Sci 2012; 103: 477–482)