Tendency For Better Survival Research Articles

Is Serum Ferritin a Predictor of Blood Transfusions Outcome and Survival in Childhood Lymphomas and Solid Tumors?

Packed red blood cell (PRBC) transfusions are an important part of supportive treatment in oncology; however, when used frequently, they can be a result of transfusion-related iron overload. The aim of the study was to evaluate the role of ferritin as a non-specific marker of neoplastic growth and transfusion-related iron overload in children with lymphomas and solid tumors. We performed a longitudinal analysis of PRBC transfusions and changes in ferritin concentrations during oncological treatment of 88 children with lymphomas and solid tumors. A ferritin concentration above 500 ng/mL was diagnosed in 14.77% of patients at the moment of admission and 18.18% at the end of treatment. No differences were shown in serum ferritin in the context of tumor type-, sex-, and transfusion-related parameters. Those above the age of 10 demonstrated higher ferritin concentrations compared to subjects younger than 5 years of age. In addition, those over than 10 years old or above 30 kg in weight showed a tendency for better survival. All tested patients demonstrated highly significant correlations between ferritin at the 15th month of treatment or after therapy discontinuation and transfusion-related parameters. Interestingly, ferritin levels were found to lower back to the values before therapy shortly after its discontinuation. Transfusion parameters and ferritin levels had no influence on the survival of the studied cancer patients.

Role of Autologous Stem Cell Transplantation in Patients with Peripheral T-Cell Lymphoma in the First Complete or Partial Remission: A Propensity Score-Matched Analysis

Background Consolidation with autologous stem cell transplantation (ASCT) was recommended for most responders to the initial peripheral T-cell lymphoma (PTCL) treatment. Evidence came primarily from retrospective studies affected by a selection bias between patients allocated to receive ASCT or not and a few prospective studies with no control groups (d'Amore F,2012; Ellin F, 2014). The National Comprehensive Cancer Network and the American Society for Transplantation and Cellular Therapy (ASTCT) recommend ASCT for patients with first-time complete remission (CR1). The European Society of Medical Oncology (ESMO) guidelines suggest that patients with first-time partial remission (PR1) could also be considered for ASCT (d'Amore F, 2015). However, the role of ASCT in patients with PTCL after CR1 or PR1 remains controversial. The COMPLETE study showed an insignificant tendency for better survival following ASCT in the PTCL with CR1 group (Park SI, 2016). The LYSA multicenter study investigated the effect of ASCT in patients with CR1 or PR1. Neither propensity score matching (PSM) nor Cox multivariate analysis supported the advantage of ASCT in upfront consolidation (Fossard G, 2018). However, well-designed randomized controlled trials to investigate the precise effect of ASCT in the front-line setting are lacking. Therefore, we aimed to investigate the efficacy of ASCT for PTCL with CR1 and PR1 by PSM analysis. Methods We pre-screened 8 826 patients with lymphoma admitted to Peking University, Cancer Hospital & Institute from January 1996 to November 2020. Patients with mature T/NK cell lymphomas were selected (n = 1 136). We excluded patients with NK/TCL or missing clinical data. Response assessment to the initial treatment was evaluated by 18F-FDG positron emission tomography/computed tomography (PET/CT) or CT using the Lugano criteria. We identified 685 patients with PTCL, of which 622 achieved CR1 or PR1. PSM was used to balance clinical indicators between the ASCT and non-ASCT groups. The primary endpoints were event-free survival (EFS) and overall survival (OS). Results Among the 622 patients who underwent initial therapy, 272 (43.7%) achieved CR1, and 147 (23.6%) achieved PR1 after the treatment. After excluding 5 patients with subsequent unknown schemes following the initial treatment, 414 were included in the final analysis (ASCT, n = 73; non-ASCT, n = 341). With a median follow-up of 5.7 years for the entire cohort, long-term survival in the ASCT group was better than in the non-ASCT group (median EFS, 8.1 vs. 2.8 years, P = 0.002; median OS, 14.9 vs. 10.2 years; P = 0.007). The 5-year EFS and OS were 66.7% (95% CI, 56.0-79.4%) and 74.7% (95% CI, 64.1-87.0%) in patients with ASCT consolidation, and 26.6% (95% CI, 23.0-30.8%) and 43.6% (95% CI, 39.2-48.4%) in patients without ASCT. After PSM, the ASCT and non-ASCT groups were similar in their disease subtypes, LDH level, Ann Abor stage, and the response to the initial treatment. The survival advantage for ASCT (n = 46), as a consolidation procedure, over non-ASCT (n = 84; median EFS. 8.1 vs 2.7 years, P = 0.007; median OS, not reached vs 7.7 years; P = 0.022; Figure 1) was maintained even after PSM. For the entire cohort, ASCT was associated with better long-term survival than non-ASCT [hazard ratio (HR) for EFS, 0.46 (95% CI, 0.28-0.76), P = 0.003; HR for OS, 0.50 (95% CI, 0.31-0.84), P = 0.008)]. Subgroup analysis showed that patients at a higher risk based on International Prognostic Index (IPI) stratifications and advanced stages might benefit significantly from ASCT. Patients with angioimmunoblastic T-cell lymphoma (AITL) in the ASCT group appeared to show better survival than those in the non-ASCT group (EFS: HR, 0.26; 95% CI, 0.10-0.66; P = 0.005; OS: HR, 0.29; 95% CI, 0.12-0.74; P = 0.009). However, ASCT endowed no survival advantage for other PTCL subtypes. Conclusion ASCT could improve the long-term survival of responders to the initial treatment among patients with PTCL, especially those with AITL. However, the specific population that could benefit most from up-front ASCT needs to be characterized further. Figure 1. EFS (A) and OS (B) after propensity score matching in the ASCT and non-ASCT groups Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Multicenter randomised trial of two versus three courses of preoperative cisplatin and fluorouracil plus docetaxel for locally advanced oesophageal squamous cell carcinoma.

The optimal number of neoadjuvant chemotherapy (NAC) cycles remains to be established for treating oesophageal squamous cell carcinoma (ESCC). We compared two versus three courses of NAC for treating locally advanced ESCC in a multi-institutional, randomised, Phase II trial. We randomly assigned 180 patients with locally advanced ESCC at 6 institutions to either two (N = 91) or three (N = 89) courses of DCF (docetaxel 70 mg/m2, cisplatin 70 mg/m2 i.v. on day 1, fluorouracil 700 mg/m2 continuous infusion for 5 days) every 3 weeks, prior to surgery. The primary endpoint was 2-year progression-free survival (PFS) with an intention-to-treat analysis. Patient background parameters were well-balanced. The R0 resection rates were 98.9 and 96.5% in the two- and three-course groups, respectively (P = 0.830). In resected cases, the two- and three-course groups had comparable pN0 rates (P = 0.225) and histological responses (P = 0.898). The 2-year PFS rate was also comparable between the two groups (71.4 vs. 71.1%, P = 0.669). Among subgroups based on baseline characteristics, only patients aged under 65 years old showed a tendency for better survival with the three-course treatment (hazard ratio = 2.612, 95% confidence interval: 1.012-7.517). Two courses of a DCF regimen showed potential as an optional NAC treatment for locally advanced ESCC. University Hospital Medical Information Network Clinical Trials Registry of Japan (identification number UMIN 000015788).

P-283 Prognostic factors in the evaluation of stage II/III squamous cell carcinoma of the anus treated with chemoradiation

Squamous cell carcinoma of the anus (SCCA) is a rare disease. Studied prognostic factors for survival in anal cancer include male sex, positive lymph node, and primary tumour size >5 cm. We aimed to perform an exploratory analysis of prognostic factors for overall survival in patients (pts) who underwent radical chemoradiation (CRT) with a standard-of-care regimen including fluoropyrimidine and mytomicin C (MMC). A retrospective analysis of stage II-III SCCA pts with PS ECOG 0-1 treated with CRT using fluoropyrimidine and MMC at a single Portuguese Oncology Unit between January 1st, 2010 and October 30th, 2020 was performed. Data cut-off was March 20th 2021. Data was obtained from pts' clinical files and analysed with SPSSv26.0, with overall survival (OS) estimation using the Kaplan-Meier method. Twenty-three pts were selected, with median (med) age of 66 years (y) [30-81], 39.1% being female. Regarding initial staging, 21.7% had stage II, 17.4% stage IIIA, and 60.9% stage IIIB. 78.3% had lymph node disease; 47.8% had tumours > 5 cm in size; 56.5% had ulcerated lesions (skin or endoscopically); 39.1% were active smokers. Med follow-up was 4 y; the OS at 4y was about 75%, with an estimated med OS 8.09 y [6.0-10.2]. We stratified our sample per LDH > 250 UI/L, haemoglobin (Hb) 5 cm, and being male. The estimated OS with LDH > 250 vs 5 cm vs 12.0 g/dL was 6.20 vs 9.85 y (p 2.85 had 6.63 vs 9.07 y (p=0.206)). For PLR, it was 151.5, but without a significant tendency (151.5 7.58 vs 8.28 y, p=0.627). In our analysis, we found a statistically significant tendency for better survival in pts with stage II-III SCCA CRT treated with Hb > 12.0 g/dL, LDH < 250 UI/L, no active smoking, and female sex. We also found an interesting tendency for better OS with a high NLR, though this was not statistically significant. These prognostic factors can be used as a tool to eventually increment the treatment aggressiveness in pts with worse prognosis.

Systemic lupus erythematosus-associated diffuse alveolar hemorrhage: a single-center, matched case-control study in China.

This study described clinical characteristics and outcome in systemic lupus erythematosus (SLE) patients with diffuse alveolar hemorrhage (DAH), and investigated risk factors and prognostic factors for DAH. We conducted a retrospective nested case-control analysis in a single-center cohort. We enrolled 94 SLE patients with DAH. For each case of DAH, two age-, sex-, and SLE courses-matched controls were randomly selected from our cohort. All patients were enrolled between 2004 and 2019 and were followed until death, end of registration with the physician's practice, or end of January 2019. We estimated the risk factors for DAH and prognostic factors for mortality using multivariate analysis. We included 4744 patients diagnosed with SLE, with 94 cases of DAH, for an incidence rate of 2.0%. DAH may occur in any stage of SLE but mostly in the early phase of disease course. Lupus nephritis (LN) was the most common concomitant involvement at DAH diagnosis. By multivariate analysis, LN, anti-SSA positivity, thrombocytopenia and elevated C-reactive protein (CRP) were significantly associated with DAH in SLE patients. All-cause mortality was increased in SLE with DAH compared with SLE without DAH (adjusted hazard ratio 6.0, 95% confidence interval 2.8-13.0, p < 0.0001). Intravenous cyclophosphamide (CTX) showed an increased tendency for better survival in DAH after adjusting for Systemic Lupus Erythematosus Disease Activity Index 2000, acute kidney injury and mechanical ventilation. LN, anti-SSA positivity, thrombocytopenia and elevated CRP were independent risk factors of DAH in lupus patients. Due to a high early death rate of DAH and little long-term damage, DAH patients may benefit from early diagnosis and intensive treatment, and CTX-based therapy can be a preferential choice.

Comparison of the prognostic difference between ypTNM and equivalent pTNM stages in esophageal squamous cell carcinoma based on the 8th edition of AJCC classification.

Objective: With the separate ypTNM stage groupings established in the 8th edition of AJCC staging system for esophageal squamous cell cancer (ESCC), we aimed to evaluate the prognostic difference between ypTNM stage and equivalent pTNM stage.Methods: ESCC patients with surgery alone (cohort 1) and patients with neoadjuvant therapy plus surgery (cohort 2) were enrolled in the study.Results: In p0, pIb, pIIa, pIIb, pIIIa, pIIIb and pIVa stages of cohort 1, the 5-year DFS and OS rates were 100/100%, 80.5/86.2%, 58.9/57.8%, 51.1/52.7%, 36.3/35.8%, 21.5/22.6% and 11.9/18.0%. In ypI, ypII, ypIII and ypIVa stages of cohort 2, the 5-year DFS and OS rates were 60.9/67.0%, 44.3/52.1%, 48.4/43.2% and 0. Patients in ypI stage had a tendency of poorer survival compared with those in pI stage (P=0.024 for DFS, P=0.067 for OS). There was no significant difference in terms of DFS (P=0.335) or OS (P=0.903) between ypII and pII. Patients in ypIII stage had a tendency of better survival compared with those in pIII stage (P=0.015 for DFS, P=0.059 for OS). Patients in ypIVa stage exhibited a significantly poorer OS compared with those in pIVa stage (P=0.038).Conclusions: With down-staged tumor after neoadjuvant therapy, survival of ypI was closed but not reached to the prognosis of equivalent pI, prognosis of ypII was similar to equivalent pII, and survival of ypIII tended to be better compared with equivalent pIII. However, without down-staged ypIVa tumor, the prognosis was worse compared with equivalent pIVa, indicating those patients were primary resistant to prescribed neoadjuvant therapy.

Preliminary result of definitive radiotherapy in patients with non-small cell lung cancer who have underlying idiopathic pulmonary fibrosis: comparison between X-ray and proton therapy

BackgroundIdiopathic pulmonary fibrosis (IPF) is associated with fatal complications after radiotherapy (RT) for lung cancer patients; however, the role of proton therapy to reduce the incidence of life-threatening complications is unclear. Herein, we present the preliminary results of early-stage lung cancer patients having IPF and treated with RT, with a focus on the comparison between X-ray and proton therapy.MethodsFrom January 2010 to October 2017, we retrospectively reviewed the medical records of 264 patients with stage I-II non-small cell lung cancer (NSCLC) treated with definitive RT alone. Ultimately, 30 patients (11.4%) who had underlying IPF were analyzed. Among these, X-ray and proton RT were delivered to 22 and 8 patients, respectively. Treatment-related complications and survival outcomes were compared between X-ray and proton therapy.ResultsThe median follow-up duration was 11 months (range, 2 to 51 months). All living patients were followed-up at least 9 months. Treatment-related death occurred in four patients (18.2%) treated with X-ray but none with proton therapy. Most patients died within one month after the onset of pulmonary symptoms in spite of aggressive treatment. In addition, the 1-year overall survival (OS) rate in patients treated with X-ray and proton was 46.4 and 66.7%, respectively, and patients treated with proton therapy showed a tendency of better survival compared to X-ray (p = 0.081). Especially, in GAP stage II and III subgroups, patients treated with proton therapy showed significantly increased survival outcomes compared to X-ray (1-year OS rate; 50.0% versus 26.4%, p = 0.036) in univariate analysis.ConclusionsRT is associated with serious treatment-related complications in patients with IPF. Proton therapy may be helpful to reduce these acute and fatal complications.Trial registrationretrospectively registered.

Anatomic resection, surgical margin positivity and primary tumor site do not have effect on overall survival after liver resection for colorectal metastases

Introduction: Liver resection performed for colorectal cancer liver metastases prologs survival even in cases of resectable extrahepatic disease. Several factors that related to disease and operation are advocated to provide survival benefit in this patient group. In here we present our ten year experience of resections performed for CRCLMs. Method: One hundred and eight patients were operated for CRCLM between January 2007 and January 2017 at Ankara University Hospitals. Patient and disease characteristics and overall survival data were obtained retrospectively from hospital records. Overall survival of patients were compared according to gender, primary tumor site, tumor T status if it was T4, liver resection type if it was anatomic resection, preoperative chemotherapy, metastasis presentation and surgical margin positivity with Log-rank Test. Overall 1, 3 and 5 year survival of all patients were calculated. Result: None of the variables mentioned above were found to have significant effect on overall survival in our cohort (p>0.05). Surgical margin negative patients, patients with metachronously presented liver metastasis and patients underwent anatomic liver resections have a non significant tendency for better survival. One-year, 3 year and 5 year survival rates were calculated 88.1%, 53.7% and 40.6% respectively. Conclusion: Although large series are needed for evaluation of these factors on survival, according to our patient cohort disease related factors and surgical approach does not have effect on survival. This Result may be the greater effect of chemotherapies on stage 4 disease. Resections performed at our center resulted comparable outcomes.

Is Height of Prognostic Significance in Breast Cancer Cases?

Objective:The objective of this study was to investigate the correlation of height with prognosis and other prognostic factors in Turkish breast cancer cases.Materials and Methods:We retrospectively reviewed a total of 393 women aged between 26 and 88 years, diagnosed with stage 1-3 invasive ductal breast cancer, treated and followed-up in Kayseri Education and Research Hospital.Findings:The mean age at admission was 55.7 years; 77.6% were aged under 65, 56.7% were postmenopausal, 97.4% had undergone modified radical mastectomy, 47.3% were AJCC stage II, 36.8% N0, 46.0% grade II, 95.4% had received chemotherapy, 81.1% radiotherapy and 71.5% hormonotherapy. Height was under 151 cm in 20.8 %, 151-160 cm in 57.3 % and over 161 in 21.9 %. Follow-up duration differed between 0.3 and 195.3 months. Mean overal survival (OS) was 125.0 (65.6-184.3) months and progression free survival was 91.5 (37.7-145.2) months, with a tendency for better survival in taller individuals but no signficant variation between height groups. The 5 and 10-year OS rates were 74.5% and 56.4%, and PFS rates were 64.5% and 49.2%. Regarding association of height with other prognostic factors, a significant correlation was found between height and AJCC stage (p= 0.011) and estrogen status (ER) (p= 0.043).Conclusion:In conclusion, overal survival was found to be longer in patients with a height between 151 and 160 cm than those under 151 cm and over 161 cm. The reason for not obtaining significant results might be a relatively small number of patients and lack of the evaluation of clinical and pathologic characteristics together with anthropometric measurements in the patient population. Further studies are warranted to clarify any association.

EBMT Prospective Non-Interventional Study On Allogeneic Hematopoietic Stem Cell Transplantation In T-Prolymphocytic Leukemia (T-PLL). Preliminary Analysis Of 43 Patients

T-PLL is very rare disease with aggressive course and poor prognosis. Our earlier retrospective study (Wiktor-Jedrzejczak et al. Leukemia 2012;26:972-6) of 41 patients with T-PLL has shown that allogeneic stem cell transplantation (allo-SCT) may provide effective disease control in some of them. However, this study (similarly to many other retrospective studies) was based on very heterogeneous material and included mainly patients with advanced disease. MethodsSince the extreme rarity of the disease and existing regulations preclude performance of prospective randomized trial in such a situation, we proposed another approach: After a careful review process expert recommendations for the diagnosis and treatment of T-PLL by allo-SCT were prepared and published on the EBMT website in 2007. Subsequently a non-interventional study on the outcome of allogeneic transplantation was initiated and continued to recruit patients until 2012. Inclusion criteria were: T-PLL diagnosed at least by immunophenotype, age between 18 and 65 years, Karnofsky performance status ≥ 60% with adequate renal and liver function, first or second-line therapy before transplantation, life-expectancy at the time of screening of at least 3 months. ResultsThis preliminary analysis covers 43 patients with T-PLL confirmed by immunophenotyping. The median age was 54 years (30 years to 63 years) and the male to female ratio was 31/12. The median time from diagnosis to transplant was 7.8 months. Twenty-six patients were in complete remission (CR), nine in partial remission, seven patients in stable or progressive disease, and one patient in unknown disease status at SCT. In line with the recommendations, 37 patients had received alemtuzumab as part of initial treatment and 6 patients did not. Donors were HLA-identical siblings in 14 patients, a matched other relative in one patient, mismatched relatives in two patients, and matched unrelated donors in 26 patients. The source of stem cells was peripheral blood in 40 patients and cord blood in 3 patients. 25 patients (58 %) received reduced intensity conditioning. In 16 patients conditioning included total body irradiation.With a median follow-up of 49.8 months in surviving patients, 3-year RFS and OS was 38% (95% CI, 25 to 57%) and 48% (95% CI, 35 to 66%), respectively. There was a tendency for better survival for patients transplanted in CR but the difference was not significant. However, non-relapse post-transplant mortality was significantly lower in this first group of patients. Other variables evaluated including use of alemtuzumab prior transplantation, type of the donor or conditioning also did not show significant differences for this number of patients. The three-year non-relapse mortality and relapse incidence were 32% and 30%, respectively. ConclusionThese data confirm that allo-HSCT may provide effective disease control in selected patients with T-PLL. Preliminary results of our prospective study seem to be better than earlier reports of retrospective analyses. In part this could be due to better patient selection and compliance with EBMT recommendations to offer allogeneic SCT early in the course of disease. Disclosures:Off Label Use: alemtuzumab, use in the pretransplantation treatment of T cell prolymphocytic leukemia.

Trends in the incidence and survival of multiple myeloma in South East England 1985-2004

BackgroundMultiple myeloma is an uncommon cancer with a poor prognosis. Its incidence is expected to increase due to ageing populations and better diagnosis, and new treatments have been developed to improve survival. Our objective was to investigate trends in the epidemiology and survival of multiple myeloma for South East England.MethodsData on 15,010 patients diagnosed with multiple myeloma between 1985 and 2004 was extracted from the Thames Cancer Registry database. We calculated the yearly age-standardised incidence rates for males and females and age-specific incidence rates in 10-year age groups for both sexes combined. We also explored geographical variation in incidence across primary care trusts. We then used period analysis to calculate trends in 1- and 5-year relative survival over the 15 years 1990-2004, comparing survival by sex and by age group 59 years and below versus 60 years and above. Finally, we investigated 5-year relative survival for the period 2000-2004 by socio-economic deprivation, assigning patients to quintiles of deprivation using the Income Domain of the Index of Multiple Deprivation 2004 based on postcode of residence.ResultsThe incidence of multiple myeloma was higher in males than in females and in patients over 70, throughout the period 1985-2004. No obvious geographical pattern of incidence by primary care trust emerged. The 1- and 5-year relative survival of male and female patients increased in both age groups and was statistically significant in males aged over 60. There was a tendency for better survival in patients resident in the most affluent areas, but this did not reach statistical significance.ConclusionsThe trends in incidence of multiple myeloma in males and females are similar to that reported from other western populations. Relative survival was higher for younger patients although we found significant improvements in 1-year relative survival for male patients over 60 years old. The improved survival demonstrated for patients of all ages is likely to reflect increased detection, earlier diagnosis and the introduction of new treatments. Future studies should investigate the influence of ethnicity on incidence and survival, and the effect of specific treatments on survival and quality of life.

Adequate extent in radical re-resection of incidental gallbladder carcinoma: analysis of the German Registry

Complete surgical resection is the only potentially curative treatment of gallbladder cancer. Gallbladder carcinoma is suspected preoperatively in 30% of patients, and 70% are incidentally discovered by the pathologist (incidental gallbladder carcinoma, IGBC). If IGBC is detected postoperatively, a re-resection, including liver resection and lymph node dissection, in T2 tumor cases and more advanced stages is recommended. It remains unclear whether the prognosis of wedge resection (2-3-cm margin) of the gallbladder bed is the same as that of resection of segments IVb/V. The German Registry, founded in 1997, aims to prospectively record all IGBC cases in Germany. In this study patients with a radical re-resection were treated according to the S3 Guidelines in Germany. The aim of this study was to clarify whether different techniques of liver re-resection show comparable results or if they differ depending on the tumor stage in IGBC patients (n = 624). A significant survival advantage in patients who have an early re-resection was observed. There was a trend of better survival in T1 tumor stage patients who undergo the less radical re-resection, especially the wedge-resection technique of 3 cm in the gallbladder bed. In T2 tumor stage patients there is a tendency for better survival with the IVb/V-resection technique compared to the 3-cm wedge resection in the gallbladder bed, and a significant survival benefit for these two techniques compared to less radical resection was evident. T3 tumor cases showed better survival with the more radical resection techniques. The wedge-resection technique combined with lymph node dissection may be the surgical strategy of choice in T1 tumor cases. For T2 tumors, IVb/V resection combined with lymph node dissection of the hepatoduodenal ligament appears to be the minimum volume of resection required. More radical procedures are needed for tumors infiltrating the serosa or beyond.

Mesenchymal Stem Cells Ameliorate Adriamycin Induced Proteinuric Nephropathy

= Abstract = Purpose : Glomerulonephropathy (GN) often manifests as proteinuria and progresses to chronic renal failure without specific therapy. Mesenchymal stem cell (MSC) has been tried as a therapeutic agent in experimental GN, and previous studies showed that administration of MSC concomitantly to the insult inducing GN or via intra-renal administration ameliorated proteinuria. The purpose of this study was to test the therapeutic potential of MSC adminis- tered via intravenous route at the time of clinically evident proteinuria. Methods : MSCs were administered intravenously via tail vain into the mice with adriamycin (ADR) induced nephropathy (ADR-GN), two weeks after ADR injection when massive proteinuria was evident. To test the capacity of MSC modulate the cytokine production in the inflammatory milieu, the concentrations of IFN- and IL-10 were measured in the su γ - pernatant of in vitro mixed lymphocyte culture (MLC) with or without additional MSC. Results : MSCs administered intravenously into the proteinuric mice with ADR-GN acce- lerated the recovery of this experimental GN with disappearance of proteinuria in two weeks when the saline treated (control) mice still showed significant proteinuria. The mice treated with MSC also had a tendency of better survival. Addition of MSC decreased IFN- and increased IL-10 in the supernatant of MLC. γ Conclusion : This study showed that MSC had a therapeutic potential even when admini- stered in a more clinically relevant setting into a proteinuric glomerulonephropathy model. Further study to verify the mechanism and long-term safety of this phenomenon is required. (J Korean Soc Pediatr Nephrol 2010;14:32-41)

Central Nervous System Relapses in Patients with Diffuse Large B Cell Lymphoma: Multicenter Retrospective Analysis in Korea

Introduction: Central nervous system (CNS) involvement in patients with diffuse large B-cell lymphoma (DLBCL) is a serious complication with a poor prognosis. Secondary CNS involvements in DLBCL are divided into 2 types as follows: CNS involvement at the time of systemic relapse or progression, and isolated CNS relapse despite systemic remission. The frequency of secondary CNS involvement is reported as variable from 4% to 27% in patients with DLBCL who did not receive CNS prophylaxis. However, there is no clear consensus as to the subset of DLBCL benefits from CNS-directed preventive therapy. Furthermore, there is no general agreement on the intensity and type of therapy against secondary CNS involvement. Thus, we analyzed the clinical features and treatment outcomes of secondary CNS involvement in patients with DLBCL.Patients and methods: We analyzed 59 patients who diagnosed with DLBCL and had secondary CNS involvement. Secondary CNS involvement was defined as a brain parenchyma lesion or leptomeningeal involvement or combined during the follow-up or during the treatment.Results: 35 patients were initially treated with CHOP or CHOP-like regimens, and 24 patients with rituximab-CHOP (R-CHOP). The median age of the patients was 54 years old (range 17–77). 37 patients (62.7%) were presented as advanced stage (7 patients with stage III, 30 patients with stage IV), and 40 patients showed elevated serum LDH. Thus, 27 patients belonged to the high-intermediate or high risk of international prognostic index (IPI). The pattern of CNS involvement was as follows: 21 had lesions of brain parenchyma, 30 leptomeningeal involvements, and 8 combined lesions. There was no clinical variable predicting a pattern of CNS involvement. We dichotomized the patients based on the onset of CNS involvement: early CNS involvement occurred within one year from diagnosis (Early CNS group, 42 patients) and delayed CNS involvement after one year (Delayed CNS group, 17 patients). The early CNS group had more advanced stage of patients (26 patients with stage IV) than delayed CNS group (4 patients with stage IV). The presence of bone marrow invasion was also significantly associated with early CNS involvement: 18 patients in early CNS involvement and 1 patient in delayed CNS involvement. In addition, high or high-intermediate risk of IPI was related with early CNS involvement (P < 0.05). The response to the primary treatment against DLBCL was not related with the onset of CNS involvement, thus 46 patients showed objective response including 33 complete responses (CR). The use of rituximab was not associated with the onset of CNS involvement. However, the number of patients with partial response (PR) was higher in the early group (9/46, 19.6%) than delayed CNS group (2/17, 11.7%). Thus, these findings suggest patients with high tumor burden represented by advanced stage, high IPI, and bone marrow invasion might have CNS involvement at the time of diagnosis. However, the overall survival was not significantly different between these two groups, and the median overall survival of patients with secondary CNS involvement was 5.13 months (95% confidence interval: 3.39–6.87 months). When we compared survival based on the type of therapy in patients with isolated brain parenchyma involvement, combined treatment approach including systemic chemotherapy (high-dosage methotreaxate (MTX) chemotherapy) and localized therapy (intrathecal MTX chemotherapy and/or whole brain radiotherapy) showed a tendency of better survival than localized therapy alone. However, the addition of systemic chemotherapy was not translated into survival benefit in patients with isolated leptomeningeal CNS involvement. Furthermore, the role of systemic chemotherapy using high-dosage MTX was not proved in patients with systemic disease progression and secondary CNS involvement although it showed the tendency of better survival.Conclusions: Patients with advanced stage, high or high-intermediate risk of IPI, and the presence of bone marrow invasion might have a high risk of secondary CNS involvement even during the active treatment. Thus, CNS prophylaxis should be considered. However, further prospective study should be warranted to determine the intensity and type of treatment against secondary CNS involvement in DLBCL.

High-dose chemotherapy with autologous stem cell transplantation in extranodal NK/T-cell lymphoma: a retrospective comparison with non-transplantation cases

To determine the role of high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) in extranodal NK/T-cell lymphoma patients, we conducted a retrospective analysis. In our previous study, we searched for patients who had received HDC/ASCT and identified 16 eligible patients and compared the treatment outcome with historical control group (n=246). Nine patients received HDC/ASCT in the first (CR1) or second complete remission (CR2), while seven patients received HDC/ASCT as salvage. Twelve of 16 patients achieved or maintained CR after HDC/ASCT. Among the 12 patients, five patients relapsed. Estimated 2-year overall survival (OS) and relapse-free survival (RFS) rates were 71.3+/-12.4% and 25.8+/-14.3%, respectively. There was a tendency of better survival in patients who received HDC/ASCT as compared to those who did not (P=0.091). In subset analysis, patients who underwent HDC/ASCT at CR (P=0.049) and patients with stage III or IV (P=0.001) had a favorable outcome. Patients with NKIPI 3,4 or EUNKTL, who underwent HDC/ASCT had more prolonged survival without statistical significance (P=0.055 and 0.056). In conclusion, HDC/ASCT may be considered as a treatment option for patients with extranodal NK/T-cell lymphoma, especially those in CR, with advanced disease (stage III/IV or EUNKTL) and high NKIPI scores.

Gelatinases and their tissue inhibitors in ovarian tumors; TIMP-1 is a predictive as well as a prognostic factor

Objective. In the present study, the significance of circulating matrix metalloproteinases -2 and -9 (MMP-2, MMP-9), as well as their tissue inhibitors -1 and -2 (TIMP-1, TIMP-2) in ovarian cancer were studied to assess the possibility of using them in clinical decision-making. Methods. We measured, prior to primary surgery, the concentrations of these proteins in serum samples of 115 patients with an ovarian tumor: 63 with cancer, 6 with a low malignant potential tumor, and 46 with a benign tumor. The measurements were performed with enzyme-linked immunosorbent assays (ELISA). The results were compared to clinicopathological data. Results. A high serum concentration of TIMP-1 at diagnosis was found to correlate with the malignant phenotype of an ovarian tumor. Within malignant neoplasias, high circulating TIMP-1 correlated to the aggressive phenotype and unfavorable prognosis. An association was found between a high serum level of TIMP-1 and an advanced stage of the disease, a residual tumor >2 cm, poor response to cytotoxic treatment, shorter recurrence free time, and shorter cancer-related overall survival. No statistically significant correlation was found between the circulating gelatinases (MMP-2, MMP-9) or TIMP-2 and the clinicopathological factors. However, a tendency for better survival with high serum concentration of TIMP-2 or MMP-2 was observed. Conclusion. We conclude that an elevated preoperative serum TIMP-1 concentration correlates to the aggressive behavior of ovarian cancer.

Enhancing the Take of Injected Adipose Tissue by a Simple Method for Concentrating Fat Cells

Injection of aspirated fat for the correction of tissue defects is a common procedure in plastic surgery. The reported rates of fat cell survival vary greatly in the medical literature, and different techniques of harvesting, processing, and reinjecting the fat cells are claimed to be responsible for these differences. However, there is no agreement concerning the best way to process the harvested fat before reinjection. The present study was initiated to examine and evaluate the effect of a simple method of isolating the fat particles on the outcome of fat graft survival. In this study, the nude mouse model was used to examine the survival and take of the fat graft concentrated before injection by the cumbersome recommended closed centrifugation technique in comparison with the authors’ recommended open method, using an operating room cotton towel as a platform for concentrating the fat cells and separating them from fluids, oil, and debris. One milliliter of concentrated human fat cells preprocessed by towel separation was injected into the nuchal subcutis of 11 nude mice in the study group, and the same amount of fat that was preprocessed by centrifugation was injected into 11 control mice. Injected fat survived in both groups. No significant differences were found regarding fat graft weight and volume, although a tendency for better survival was noticed in the experimental group. Histologic evaluation of the grafts revealed significantly less fibrosis within the study group, meaning that the quality of the fat grafts was better. The authors found this method to be simple, cheap, and friendly to the surgeon in comparison with traditional processing using the centrifuge.

Autologous stem cell transplantation in multiple myeloma: improved survival in nonsecretory multiple myeloma but lack of influence of age, status at transplant, previous treatment and conditioning regimen. A single-centre experience in 127 patients.

High-dose therapy with autologous stem cell transplantation (ASCT) has become the treatment of choice for symptomatic eligible patients with multiple myeloma (MM). We report our centre experience and analyse retrospectively the prognostic influence of pretransplant characteristics and transplant modalities on response and survival. A total of 127 MM patients (median age: 55.2 years) were transplanted between 1994 and 2001. In all, 69 patients had IgG, 28 IgA, 23 light chain, one IgD and six non secretory MM. At the time of autograft, 6% of patients were in complete remission (CR), 73% in partial remission (PR), 12% showed minor response to previous treatment and 9% had stable or refractory disease. Prior to autograft, 79% of cases had received only one line of chemotherapy and 21% two or more lines. All patients received PBSC support after conditioning with 200 mg/m(2) melphalan alone (100 patients) or melphalan and TBI (27 patients). We evaluated the influence of age (using as cutoff value the ages of 55, 60 and 65 years), type of MM, status pre- and post-ASCT, number of lines of previous regimens, time of ASCT from diagnosis, year of autograft, dose of reinfused CD34+ cells, plasma cell infiltration and beta(2)-microglobulin at diagnosis on overall (OS) and progression-free survivals (PFS) to define patients with better prognosis. Following ASCT, 15% of patients were in CR and 81% in PR, while only two patients progressed. Median OS and PFS from transplantation were 50.4 and 23.5 months, respectively. Median OS from diagnosis was 79.7 months. Transplant-related mortality was 2.3%. Low levels of beta(2)-microglobulin and the achievement of CR post-transplant correlated with longer PFS (P<0.03 and P<0.01, respectively). The median PFS was 36.1, 23.9, 21.1 and 16.4 months for nonsecretory, IgG, IgA and light chain subtypes, respectively. Age was not an important prognostic factor at a cutoff value of 55 or 60 years. We conclude that ASCT is a safe and effective procedure even in resistant cases. The outcome was independent of age, time from diagnosis, previous treatment and conditioning regimen, but there was a tendency for better survival in the nonsecretory patients.

Thyroid transcription factor-1 (TTF-1) expression in human lung carcinomas: its prognostic implication and relationship with wxpressions of p53 and Ki-67 proteins.

This study was aimed to evaluate the prevalence and prognostic implication of thyroid transcription factor-1 (TTF-1) immunoreactivity in 81 human lung carcinomas, including 65 cases of non-small cell lung carcinoma (NSCLC) and 16 cases of small cell lung carcinoma (SCLC); and also to investigate its relationship with the cell proliferation and regulation by immunostaining of Ki-67 and p53 proteins, respectively. The immunohistochemical staining for TTF-1 (clone 8G7G3/1) was performed and several clinicopathologic variables and the follow-up data were obtained. The immunostaining results for TTF-1 were semiquantitatively interpreted as negative and positive. Of NSCLCs, TTF-1 is highly expressed in adenocarcinomas (76%), whereas squamous cell carcinomas revealed no immunoreactivity (0%). SCLCs showed strong TTF-1 expression (88%). In NSCLC, TTF-1 expression was inversely correlated with Ki-67 proliferative activity and independent of p53 overexpression. TTF-1 (+) group tended to show better survival than TTF-1 (-) group in NSCLC. Conclusively, these observations suggest that TTF-1 is a sensitive and specific diagnostic marker for pulmonary adenocarcinomas and SCLCs; that TTF-1 might have a good prognostic implication based on its inverse correlation with Ki-67 proliferative activity and tendency for better survival in NSCLC; that this cell lineage marker may play a role in the molecular pathogenesis of lung cancers at the level of transcription.

Adjuvant whole abdominal radiotherapy in epithelial cancer of the ovary

Purpose: To reexamine the use of adjuvant radiotherapy in optimally debulked patients.Methods and Materials: Between January 1985 and April 1998, 60 patients were treated with adjuvant whole abdominal radiotherapy (A-WART). The stage distribution was Stage IC in 17 patients, Stage II in 9, and Stage III in 34. The grade distribution was Grade 1 in 9 patients, Grade 2 in 27, and Grade 3 in 24; thus, 60% of the patients had Stage III disease and 40% had Grade 3 tumors. After surgery, no residuum was left in 42 (70%), ≤2 cm in 13 (22%), and >2 cm in 5 (8%) of 60 patients. Of the 60 patients, 19 also received platinum-based chemotherapy; in 12 of the 19, the chemotherapy was before A-WART. Thirty-seven of the patients had undergone previous abdominal procedures and a second-look operation was performed in 25% of them. A-WART consisted of 22 Gy in 22 fractions, at 5 fractions weekly in 90% of the patients. The remaining 10% received 25 Gy in 25 fractions within 5 weeks. The A-WART was delivered using a 4-MV linear accelerator. After abdominal irradiation, a boost to the pelvis was given to reach 45 Gy at 1.8 cGy/fraction, using a 4–15-MV linear accelerator.Results: Treatment was delivered in a median of 50 days (range 48–70). In 12 (20%) of the 60 patients, a transient treatment interruption occurred because of acute toxicity, mainly vomiting and diarrhea. The overall survival rate was 55% at 5 years (median follow-up 96.5 months). Patients with low-histologic grade tumors (Grade 1-2) had a better 5-year survival rate (66%) than those with Grade 3 tumors (35%; p <0.03). A tendency for better survival was found for those with Stage I-II than for those with Stage III (69% vs. 43%). Nonetheless, this difference did not reach statistical significance (p = 0.17). For patients receiving chemotherapy, the 5-year survival rate was 51%, not statistically different from the 58% 5-year survival rate observed among those patients without adjuvant chemotherapy (p = 0.9). The abdominal control rate was 83%. Thirty-five percent of the patients sustained acute Grade 2-3 complications. Late complications were observed in 6 of 60 patients, 4 had Grade 3 (7%) and 2 had Grade 4 (3%). Two patients died of intestinal occlusion, both had undergone previous abdominal procedures and in 1, no tumor was found in the abdomen at the postmortem examination.Conclusion: A-WART achieves a quite favorable 5-year survival rate with a low complication rate in properly selected patients. A-WART should be included in the elective postoperative treatment of ovarian cancer patients who are at risk of abdominal failure, and this should be explored in a randomized trial.