High Serum Levels Of Lactate Dehydrogenase Research Articles

Prediction of SARS-CoV-2-Related Lung Inflammation Spreading by V:ERITAS (Vanvitelli Early Recognition of Inflamed Thoracic Areas Spreading).

Background Coronavirus disease 2019 (COVID-19) can be complicated by interstitial pneumonia, possibly leading to severe acute respiratory failure and death. Because of variable evolution ranging from asymptomatic cases to the need for invasive ventilation, COVID-19 outcomes cannot be precisely predicted on admission. The aim of this study was to provide a simple tool able to predict the outcome of COVID-19 pneumonia on admission to a low-intensity ward in order to better plan management strategies for these patients. Methods The clinical records of 123 eligible patients were reviewed. The following variables were analyzed on admission: chest computed tomography severity score (CTSS), PaO2/FiO2 ratio, lactate dehydrogenase (LDH), neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio, C-reactive protein (CRP), fibrinogen, D-dimer, aspartate aminotransferase (AST), alanine aminotransferase, alkaline phosphatase, and albumin. The main outcome was the intensity of respiratory support (RS). To simplify the statistical analysis, patients were split into two main groups: those requiring no or low/moderate oxygen support (group 1); and those needing subintensive/intensive RS up to mechanical ventilation (group 2). Results The RS intensity was significantly associated with higher CTSS and NLR scores; lower PaO2/FiO2 ratios; and higher serum levels of LDH, CRP, D-dimer, and AST. After multivariate logistic regression and ROC curve analysis, CTSS and LDH were shown to be the best predictors of respiratory function worsening. Conclusions Two easy-to-obtain parameters (CTSS and LDH) were able to reliably predict a worse evolution of COVID-19 pneumonia with values of >7 and >328 U/L, respectively.

Poor prognostic factors of Sézary syndrome: A retrospective single‐center study from Japan

AbstractObjectivesAlthough the prognosis of Sézary syndrome (SS) is highly unfavorable, the prognostic factors have not been fully understood. In this study, we tried to investigate the prognostic factors in Japanese SS patients for the first time.MethodsWe performed a retrospective cohort study of 19 SS patients who visited our hospital between January 1, 1999, and December 31, 2019. The collected clinical findings were age, gender, performance status (PS), and TNMB staging at diagnosis. TNMB staging was determined according to the International Society for Cutaneous Lymphomas and the cutaneous task force of the European Organization of Research and Treatment of Cancer criteria. The collected hematological findings were serum levels of soluble IL‐2 receptor (sIL‐2R), lactate dehydrogenase (LDH), thymus and activation‐regulated chemokine (TARC), and immunoglobulin E (IgE), Sézary cell count, Sézary cell ratio among white blood cells, and eosinophil count in peripheral blood at diagnosis.ResultsWe analyzed the correlations between overall survival and various clinical and hematological findings. In the log‐rank test, PS1‐3, N2‐3 stage, higher serum levels of LDH (≥355 IU/L), sIL‐2R (≥1729 U/ml) and TARC (≥19,867 pg/ml), and higher Sézary cell count (≥7480/μl) and Sézary cell ratio among white blood cells (≥52%) at diagnosis were associated with decreased overall survival.ConclusionsThis is the first report evaluating prognostic factors in Asian SS patients. This study may contribute to selecting the treatment strategy and improving survival and quality of life of Asian SS patients.

Serum and salivary levels of lactate dehydrogenase in oral squamous cell carcinoma, oral lichen planus and oral lichenoid reaction

BackgroundIncreased levels of lactate dehydrogenase (LDH) as a tumor marker have been reported in malignant and some premalignant oral lesions such as oral lichen planus (OLP) and oral lichenoid reactions (OLRs). This study aimed to assess the level of total LDH in the saliva and serum of patients with oral squamous cell carcinoma (OSCC), OLP and OLRs.MethodsIn this case–control study, the participants were divided into four groups (n = 25) of healthy controls, OLP, OLRs, and OSCC. The serum and stimulated/unstimulated salivary levels of LDH were spectrophotometrically measured using standard LDH kits (Pars Azmoun). One-way ANOVA, Chi-square test, Pearson’s correlation test, and receiver operating characteristic (ROC) analysis were applied to analyze the data.ResultsThe serum and salivary levels of LDH in OSCC patients were significantly higher than that the corresponding values in other groups (P = 0.0001). The serum level of LDH in OLR group was significantly higher than that in the control and OLP groups (P = 0.0001), but the difference in salivary level of LDH was not significant. The ROC analysis showed that both the serum and salivary levels of LDH had significant diagnostic ability for detection of OSCC and OLRs. Significant associations were noted between the serum and salivary levels of LDH.ConclusionsPatients with OSCC and OLRs had higher serum levels of LDH than OLP and control groups. Further prospective longitudinal studies are required to assess the tissue level of LDH and monitor the transformation of OLRs because they have low rate of malignant transformation compared with other oral premalignant lesions.

Programmed cell death protein 1 inhibitors in advanced cutaneous squamous cell carcinoma: real-world data of a retrospective, multicenter study

BackgroundCutaneous squamous cell carcinoma (cSCC) is one of the most common malignancies of the skin. Even though most patients are sufficiently treated by surgical resection, some will eventually metastasize and need systemic therapy. Phase I and II studies have shown efficacy for programmed cell death protein 1 (PD-1) inhibitors, but cohort sizes are low and real-world data especially on long-term outcome are pending. MethodsPatients from six German skin cancer centers treated with PD-1 inhibitors (pembrolizumab, nivolumab or cemiplimab) for advanced cSCC were retrospectively studied. Internal patient records were analyzed for clinical outcome including response, progression-free survival (PFS), overall survival (OS) and toxicity. ResultsOf 46 evaluable patients (median age: 76 years), the overall response rate (RR) was 58.7%, including 15.2% with complete response. The disease control rate was 80.4%. Both median PFS and OS were not reached, Kaplan–Meier estimated 1-year PFS was 58.8%. Patients responding to therapy showed durable remission. Response was independent of the PD-1 inhibitor used and also independent of the presence of distant metastases vs. locally advanced disease. Two predictive factors were found: Patients with primaries located on the leg had a poorer therapy outcome and patients with high lactate dehydrogenase serum levels at baseline. Treatment was overall tolerated well, with less than 10% of patients discontinuing therapy due to toxicity. ConclusionsPD-1 inhibitors fulfill the need for an efficient systemic therapy for advanced cSCC and should be the new standard of care. With high RRs and durable disease control, neoadjuvant and adjuvant regimens should be evaluated.

Abstract 1003: A link between lactate dehydrogenase A, lactate and tumor phenotype identified by imaging

Abstract Metabolic changes in primary tumors have a significant impact on tumor progression and on the development of the metastatic phenotype. In cancer patients, serum total lactate dehydrogenase (LDH) levels are often increased, and the gene for LDH-A protein, is frequently upregulated in tumors (Koukourakis, Giatromanolaki et al. 2003). These features have been linked to poor prognosis, and a greater metastatic potential has been reported in patients with high LDH serum levels. Since LDH-A protein is required for the maintenance and progression of many tumors (Fantin, St-Pierre et al. 2006), it is also becoming a potential target for cancer therapy (Le, Cooper et al. 2010; Seth, Grant et al. 2011). We investigated the relationship between LDH-A expression and lactate production in two isogenic breast cancer lines (67NR and 4T1) (Serganova, Rizwan et al. 2011). These two cell lines were derived from a single mammary tumor that developed spontaneously in a BALB/c mouse. Each subclone was shown to have different phenotypic properties (Aslakson and Miller 1992). LDH-A expression, lactate concentration, glucose utilization and oxygen consumption were measured in cells, and the potential relationship between tumor lactate levels (measured by magnetic resonance spectroscopic imaging (MRSI)) and tumor glucose utilization (measured by [18F] 2-deoxy-2-fluoro-D-glucose positron emission tomography ([18F]FDG-PET)) was assessed in orthotopic breast tumors derived from these cell lines. We show a substantial difference in LDH-A expression between 67NR and 4T1 cells under normoxia and hypoxia. We also show that small orthotopic 4T1 tumors generate ten-fold more lactate than corresponding 67NR tumors. The high lactate levels in small primary 4T1 tumors are associated with intense pimonidazole staining (a hypoxia indicator). Less intense hypoxia staining was observed in the larger 67NR tumors, and is consistent with the gradual increase and plateau of lactate concentration in enlarging 67NR tumors. We show that lactate-MRSI has a greater dynamic range than [18F]FDG-PET and may be a more sensitive measure to evaluate the aggressive and metastatic potential of primary breast tumors. We hypothesized that tumor lactate levels monitored by MRSI will reflect LDH-A enzymatic activity and tumor phenotype. We also suggest that lactate-MRSI is a more sensitive measure than [18F]FDG-PET, and could be used in the clinic to evaluate the aggressive potential of primary breast tumors. Aslakson, C. J. and F. R. Miller (1992). Cancer Res 52(6): 1399-1405. Fantin, V. R., J. St-Pierre, et al. (2006). Cancer Cell 9(6): 425-434. Koukourakis, M. I., A. Giatromanolaki, et al. (2003). Br J Cancer 89(5): 877-885.Le, A., C. R. Cooper, et al. (2010). Proc Natl Acad Sci U S A 107(5): 2037-2042. Serganova, I., A. Rizwan, et al. (2011). Clin Cancer Res 17(19): 6250-6261. Seth, P., A. Grant, et al. (2011). Neoplasia 13(1): 60-71. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1003. doi:1538-7445.AM2012-1003

390 Enhanced suppression of Raf-1 activity by K vitamins mediates their synergy with Sorafenib to inhibit HCC cell growth in vitro and in vivo

Anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK)-negative (ALCL-ALK−) is a provisional entity in the WHO 2008 Classification that represents 2–3% of NHL and 12% of T-cell NHL. No particular risk factor has been clearly identified for ALCL, but a recent study showed an odds ratio of 18 for ALCL associated with breast implants. Usually, the architecture of involved organs is eroded by solid, cohesive sheets of neoplastic cells, with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) and classical Hodgkin lymphoma being the main differential diagnoses. In this regard, staining for PAX5 and CD30 is useful. Translocations involving ALK are absent, TCR genes are clonally rearranged. CGH and GEP studies suggest a tendency of ALCL-ALK− to differ both from PTCL-NOS and from ALCL-ALK+.Patients with ALCL-ALK− are usually adults with a median age of 54–61 years, and a male-to-female ratio of 0.9. At presentation, ALCL-ALK− is often in III–IV stage, with B symptoms, high International Prognostic Index score, high lactate dehydrogenase serum levels, and an aggressive course. ALCL-ALK− presents with lymph node involvement in ∼50% of cases; extranodal spread (20%) is less common. Staging work-up for ALCL-ALK− is similar to that routinely used for nodal NHL. Overall prognosis is poor, with a 5-year OS of 30–49%, which is significantly worse when compared to OS reported in patients with ALCL-ALK+ (5-year: 70–86%). Patients with systemic ALCL exhibit a significantly better survival compared with patients with PTCL-NOS, with a 5-year OS of 51% and 32%, respectively. Age, PIT scoring system, β2-microglobulin, and bone marrow infiltration are the main prognostic factors. The expression of proteins involved in the regulation of apoptosis (caspase 3, Bcl-2, PI9) and of CD56 is related to clinical outcome.ALCL-ALK− is generally responsive to doxorubicin-containing chemotherapy, but relapses are frequent. CHOP is the most commonly used regimen to treat systemic ALCL with complete remission rates of 56%, and a 10-year DFS of 28%. Encouraging results have been reported with more intensive chemotherapy regimens. The addition of etoposide improved outcome. Alemtuxumab-CHOP regimen was associated with excellent remission rate but increased toxicity. The role of high-dose chemotherapy supported by ASCT has not been investigated in a trial of exclusively ALCL patients. When used in first remission, it was associated with a 5-year PFS of 64%. High-dose chemotherapy with ASCT is the standard therapeutic option for patients with relapsed or refractory disease. The role of allogeneic transplantation in patients with relapsed/refractory ALCL remains to be defined but there are data to support the contention that a graft-versus-lymphoma effect does exist. Myeloablative conditioning has been associated with 5-year PFS and OS of 40% and 41%, respectively, but a 5-year TRM of 33% was reported. Allo-SCT can be an option for relapsed/refractory ALCL in younger patients, preferably in the setting of a clinical trial.Pralatrexate, anti-CD30 monoclonal antibodies, brentuximab vedotin (SGN-35) in particular, 131I-anti-CD45 radioantibody, yttrium-anti-CD25 radioimmunoconjugates, histone deacetylase inhibitors, bortezomib, gemcitabine, vorinostat, lenalidomide, and their combinations represent the most appealing chemotherapy and/or targeted agents to be investigated in future trials.

Serum and Tissue LDH Levels in Patients with Breast/Gynaecological Cancer and Benign Diseases

Background: Lactate dehydrogenase A (LDHA) is involved in anaerobic glycolysis. In cancer patients, serum total lactate dehydrogenase (LDH) levels are often increased, and the gene for one of its isoenzymes, LDHA, is up-regulated. These features have been linked to poor prognosis in several studies. Methods: We investigated comparatively the total serum LDH activity and tissue isoenzyme LDH5 and hypoxia-inducible factor 1α (HIF1α) levels in patients with breast (n = 18) and gynaecological (n = 23) malignancies and benign diseases (n =54). Results: The serum LDH levels were significantly higher in patients with endometrial adenocarcinoma (349 ± 100 IU/l) and ovarian cystadenocarcinomas (383 ± 116 IU/l) compared to healthy controls (256 ± 68 IU/l) (p values 0.01 and 0.006, respectively). This difference did not reach significance in patients with breast cancer (328 ± 169 IU/l; p = 0.17)). Uterine leiomyoma patients showed intermediate LDH levels (310 ± 81 IU/l), while patients with breast fibroadenomas and ovarian cystadenomas had LDH serum levels close to carcinomas (308 ± 60 and 348 ± 135 IU/l, respectively). LDH5 isoenzyme was strongly expressed in cancer cells, exhibiting a mixed cytoplasmic/nuclear subcellular pattern. Interestingly, a high LDH5 content in tissue sections was not invariably accompanied by high LDH serum levels. High HIF1α tissue expression was linked to high tissue LDH5 expression. Conclusion: Serum and tissue LDH is up-regulated in gynaecologic and breast malignancies and in a subset of benign conditions such as fibro- and cystadenomas. The release of LDH, however, in the bloodstream is partly related to the LDHA gene up-regulation.

Treatment Outcome and Prognostic Factors for Children with Advanced Non-Hodgkin's Lymphoma at a Single Institution

Background: Non-Hodgkin's lymphoma (NHL) accounts for over 80% of pediatric malignant lymphoma in Korea; the event free survival (EFS) of advanced stage NHL has been reported to be 60 to 70%. We accessed the outcome of advanced stage pediatric NHL at a single institution. Methods: Pediatric patients who were diagnosed as stage 3 or 4 with NHL from May 1991 to June 2004 at Asan Medical Center were analyzed for outcomes according to histopathology, gender, age at present, involvement of bone marrow or central nervous system (CNS), and serum level of lactate dehydrogenase (LDH). Results: Sixty-three patients were enrolled in this study. The head and neck were the most common primary site. The five-year EFS and overall survival (OS) were 68% and 78%, respectively. Five-year EFS for lymphoblastic, Burkitt, anaplastic large cell and diffu se large B cell lymphoma were 62%, 86%, 74% and 63%, respectively. Five-year EFS and OS for patients with LDH≤500IU/L were 85% and 100%, while those with LDH>500IU/L were 64% and 72% (P=0.04). There was no significant difference in EFS or OS with regard to other factors. Sixteen out of the 63 patients relapsed, and the five-year OS for those who relapsed was 44%. Conclusion: The outcome of patients with advanced stage NHL treated at our institution was comparable with previous reports. High serum level of LDH at diagnosis proved to be a poor prognostic factor. New effective treatment regimens are needed to improve the outcome of pediatric patients with relapsed NHL.

Prognostic Significance of Serum Lactate Dehydrogenase in Osteosarcoma of the Extremity: Experience at Rizzoli on 1421 Patients Treated over the Last 30 Years

The study evaluated the correlation between pretreatment serum lactate dehydrogenase (LDH) levels with the stage of disease and its clinical prognostic value. Pretreatment serum LDH of 1421 patients with osteosarcoma of the extremity were assessed to investigate whether the enzyme correlates with the stage of the tumor. In 860 assessable patients with localized disease, treated according to 10 different protocols of adjuvant (four) and neoadjuvant chemotherapy (six), we also evaluated the correlation between the serum levels of LDH and outcome. According to the stage of disease, the rate of high serum level of LDH was significantly higher in 199 patients with metastatic disease at presentation than in 1222 patients with localized disease (36.6% vs 18.8%; P < 0.0001). In these patients, the 5-year disease-free survival was 39.5% for patients with high LDH levels and 60% for those with normal values. The 5-year disease-free survival correlated with serum level of LDH at univariate and multivariate analysis, although it lost its significance when histologic response to chemotherapy was also considered in the multivarite analysis. Serum LDH has a prognostic value and it should be considered in evaluating the results of therapeutic trials of chemotherapy, as well as defining a category of patients at high-risk of relapse to be treated with a more aggressive regimen.