Significant Higher Survival Rate Research Articles

Increased R-spondin 3 contributes to aerobic exercise-induced protection against renal vascular endothelial hyperpermeability and acute kidney injury.

Exercise training exerts protective effects against sepsis-associated multiple organ dysfunction. This study aimed to investigate whether aerobic exercise protected against sepsis-associated acute kidney injury (AKI) via modulating R-spondin 3 (RSPO3) expression. To investigate the effects of aerobic exercise on lipopolysaccharide (LPS)-induced AKI, LPS (20 mg/kg) was intraperitoneally injected after six weeks of treadmill training. To investigate the role of RSPO3 in LPS-induced AKI, wild-type (WT) or inducible endothelial cell-specific RSPO3 knockout (RSPO3EC-/- ) mice were intraperitoneally injected with 12 mg/kg LPS. RSPO3 was intraperitoneally injected 30 min before LPS treatment. Aerobic exercise-trained mice were more resistant to LPS-induced body weight loss and hypothermia and had a significant higher survival rate than sedentary mice exposed to LPS. Exercise training restored the LPS-induced decreases in serum and renal RSPO3 levels. Exercise or RSPO3 attenuated, whereas inducible endothelial cell-specific RSPO3 knockout exacerbated LPS-induced renal glycocalyx loss, endothelial hyperpermeability, inflammation, and AKI. Bioinformatics analysis results revealed significant increases in the expression of matrix metalloproteinases (MMPs) in kidney tissues of mice exposed to sepsis or endotoxaemia, which was validated in renal tissue from LPS-exposed mice and LPS-treated human microvascular endothelial cells (HMVECs). Both RSPO3 and MMPs inhibitor restored LPS-induced downregulation of tight junction protein, adherens junction protein, and glycocalyx components, thus ameliorating LPS-induced endothelial leakage. Exercise or RSPO3 reversed LPS-induced upregulation of MMPs in renal tissues. Increased renal expression of RSPO3 contributes to aerobic exercise-induced protection against LPS-induced renal endothelial hyperpermeability and AKI by suppressing MMPs-mediated disruption of glycocalyx and tight and adherens junctions.

Impacts of dietary supplementation of bamboo vinegar and charcoal powder on growth performance, intestinal morphology, and gut microflora of large-scale loach Paramisgurnus dabryanus.

Although accumulating data demonstrate that dietary supplementation of bamboo vinegar and charcoal powder (BVC) can significantly strengthen the immunity and boost the growth of domestic animals, its application potency still awaits verification in commercial fish species such as the large-scale loach Paramisgurnus dabryanus. The impacts of 90-day dietary supplementation of 1% and 2% BVC on survival and growth performance of the loach, and on the intestinal morphological characteristics and gut microflora were analyzed. Our data show that the large-scale loach supplied with BVC at the experimental doses had significant higher survival rates and better growth performance (indicated by greater weight gain (1.13-1.14 times), higher specific growth rate (1.04 times), and lower feed conversion ratio (0.88-0.89 times)) compared to that of the control (P<0.05). Histological examination revealed significant longer villus (3.22-5.54 times), deeper crypt (1.77-1.87 times), and thicker muscle (1.59-3.17 times) in the intestines of large-scale loach fed with BVC (P<0.05). Furthermore, we found that the gut microflora consisted of significantly fewer proportions of potential pathogenic bacterial species (Aeromonas veronii and Escherichia coli), but significantly greater proportions of beneficial microbes (Lactococus raffinolactis and Faecalibacterium prausnitzii). Therefore, dietary intake of BVC can promote intestinal tract development and optimize gut microflora, by which the survival and growth of large-scale loach may be improved.

Impact of sarA Mutation on Immune System Evasion and Stress Response in Staphylococcus aureus

Background: Staphylococcus aureus is a major human pathogen responsible for a large number of infections. In S. aureus, SarA is an important global locus responsible for the regulation of virulence factors, as well as biofilm formation. Objectives: The aim of this work is to clarify the impact of SarA on biofilm formation, immune system evasion, as well as the survival of S. aureus under stress conditions. Methodology: A comparative study between S. aureus wild type strain, sarA mutant and complemented strains was established addressing the biofilm formation, opsonization, phagocytosis, as well as ability of the bacterium to survive in stressful environments including acidic pH, hyperosmotic and oxidative stress. The in vitro experiments were confirmed by challenging of mice via intraperitoneal injection with the wild type strain, sarA mutant and complemented strains. Results: Mutation of sarA diminished significantly biofilm formation. Moreover, this mutation resulted in a slight decrease in the deposition of the most important opsonin in complement-mediated immunity, named C3 on S. aureus cells. However, this mutation was associated with a significant enhancement of bacterial phagocytosis and killing by human neutrophils. Furthermore, this mutation altered bacterial survival in stressful conditions. It is also noteworthy that sarA mutation resulted in a significant higher survival rates during the challenging of mice. Conclusion: SarA plays a role as a key regulator of biofilm formation, which in turn has a great impact on immune system evasion through affecting opsonization and phagocytosis. In addition, SarA improves the ability of S. aureus to survive in stressful conditions.

Recombinant DnaK Orally Administered Protects Axenic European Sea Bass Against Vibriosis.

Vibrio anguillarum causes high mortality in European sea bass (Dicentrarchus labrax) larviculture and is a hindering factor for successful sustainable aquaculture of this commercially valuable species. Priming of the innate immune system through administration of immunostimulants has become an important approach to control disease outbreaks in marine fish larviculture. This study was conducted to evaluate immunostimulation by Escherichia coli HSP70 (DnaK) in axenic European sea bass larvae in order to protect the larvae against vibriosis. DnaK stimulates the immune response in crustaceans and juvenile fish against bacterial infections. The use of axenic fish larvae allows to study immunostimulation in the absence of an interfering microbial community. At 7 days post-hatching, larvae received a single dose of alginate encapsulated recombinant DnaK. Two non-treated control groups in which animals either received empty alginate microparticles (C1) or no alginante microparticles (C2 and C3) were included in the study. Eighteen hours later, all larvae, except the ones from group C3 (non-infected control) were challenged with V. anguillarum (105 CFU, bath infection). Mortality was daily recorded until 120 h post infection and at 18, 24, and 36 h post infection, larvae were sampled for expression of immune related genes. Results showed that V. anguillarum induced an immune response in axenic sea bass larvae but that the innate immune response was incapable to protect the larvae against deadly septicaemic disease. In addition, we showed that administration of alginate encapsulated DnaK to axenic European sea bass larvae at DAH7 resulted in a significant, DnaK dose dependent, upreglation of immune sensor, regulatory and effector genes. Significant upregulation of cxcr4, cas1 and especially of hep and dic was correlated with significant higher survival rates in V. anguillarum infected larvae. In the future recombinant DnaK might perhaps be used as a novel immunostimulant in sea bass larviculture.

Mid-term results after revision total hip arthroplasty with custom-made acetabular implants in patients with Paprosky III acetabular bone loss.

Severe acetabular bone loss, both with or without pelvic discontinuity, remains a challenge in revision total hip arthroplasty (RTHA). The goal of our study was to evaluate the mid-term results for consecutive patients with Paprosky III acetabular bone loss with or without pelvic discontinuity who needed RTHA with custom-made acetabular implants and to compare the results to those of other studies. Sixty-eight (68) patients with severe acetabular bone loss (Paprosky Type IIIa and IIIb), who required RTHA, were included in our study. All prostheses were constructed on the basis of thin-layer computed tomography (CT) scans of the pelvis. The visual analogue scale (VAS), Harrison hip score (HHS), and clinical and radiographic follow-up assessments were used to evaluate the outcome. The average follow-up time was 43months (range 1-120months). Implant survival at last follow-up was 75% (51 of 68). Kaplan-Meier survival analysis, with explantation as the endpoint, revealed survival rates of 82.7% (3years) and 77% (5years). Patients with revision of the acetabular component only had a significant higher survival rate (p 0.012). Overall revision rate was 36.7%. Reinfection rate was 34.4%. Complications included 15 (22%) periprosthetic joint infections (PJI), 7 dislocations (10.2%), and 2 aseptic loosenings (2.9%). Mean VAS at last follow-up was 1.45 compared to 3.2 preoperatively, while mean HHS improved from 21.1 points preoperatively to 61 at last follow-up. The change in both scores was thus significant (p < 0.001). Defect reconstruction with custom-made modular acetabular implants can be a good, nevertheless expensive, treatment option with clinically and radiologically satisfying results in comparison to recent studies in the literature. Nevertheless, high postoperative complication rates, especially in terms of PJI, remain a challenge.

EP1.17-08 Good Survival in Females Undergoing Surgery Without Adjuvant Chemotherapy for Stage Three Lung Cancer: A Review of Our 12-Year Experience

Lung cancer is a major disease in Singapore. Anatomical surgical resection is the treatment of choice for early lung cancer. No study on outcome of surgery on early lung cancer has been reported in a mixed Asian population. We aim to review the outcome of patients with early lung cancer who underwent surgery in our tertiary centre. We performed a retrospective cross-sectional study on all patients who underwent lung resection between 1st January 2006 and 31st December 2017. Information collected included patient”s age, gender, race, stage of disease and outcome data. Those with a diagnosis of primary lung cancer were included whilst those whose surgery was not for curative intent were excluded. 404 patients are included in our study. The mean age is 62.9 years with the modal age group between 60 and 69 years old. Females are significantly younger than males (mean 61.6 years vs 64.0 years, p = 0.019). 76.6% (n = 310) are early disease (Stage 1 or Stage 2) and 20.0% (n = 81) are late disease (Stage 3). Overall survival is significantly higher in early than late disease and in females than males. In female patients with Stage 3 disease, there is no significant difference in 1-year survival between early (97.3%) and late (89.7%) (p = 0.177) disease. Those aged between 70 and 79 years has a significantly higher mortality at 3 years (27.3%, odds ratio 3.73 (1.0 – 13.5, CI 95%)). There is no significant difference in 3 year mortality between early and late disease in females younger than 60 years old (87.5% vs 77.8%, p = 0.303). T3/T4 disease patients have better survival rates than N2 disease patients. All female patients with T3/T4 disease are still alive at 5 years even in those without adjuvant chemotherapy. In females with N2 disease, 3 and 5-year survival is also higher in patients with partial or no adjuvant chemotherapy but this is not statistically significant. The use of adjuvant chemotherapy is also associated with a significant higher rate of recurrence (53.5% vs 16.1%, p = 0.001) in all patients with Stage 3 disease, especially in female patients (68.2% vs 18.2%, p = 0.009). In females with N2 disease, the recurrence rate is significantly higher in those who had adjuvant chemotherapy (68.4% vs 25.0%, p = 0.049). For those with T3/T4 disease, there is no recurrence in patients who did not have any adjuvant chemotherapy but this is not statistically significant. Our study demonstrate that female patients with early lung cancer present earlier and have significant higher survival rates than males. Even in patients with stage 3 disease, there is good survival benefit up to 3 years post-surgery for patients aged 60 years old and below. Three and five year survival are better in female patients with N2 disease who did not have or did not complete their adjuvant chemotherapy than those who did. The use of adjuvant chemotherapy is also associated with a higher rate of recurrence, especially in females with N2 disease.

Effects of dietary Gelsemium elegans alkaloids on growth performance, immune responses and disease resistance of Megalobrama amblycephala

The present study aim to investigate the effects of dietary Gelsemium elegans alkaloids supplementation in Megalobrama amblycephala. A basal diet supplemented with 0, 5, 10, 20 and 40 mg/kg G. elegans alkaloids were fed to M. amblycephala for 12 weeks. The study indicated that dietary 20 mg/kg and 40 mg/kg G. elegans alkaloids supplementation could significantly improve final body weight (FBW), weight gain rate (WGR), specific growth rate (SGR), feed conversion ratio (FCR) and protein efficiency ratio (PER) (P < 0.05). The 20 mg/kg and 40 mg/kg G. elegans alkaloids groups showed significantly higher whole body and muscle crude protein and crude lipid contents compared to the control group (P < 0.05). The amino acid contents in muscle were also significantly increased in 20 mg/kg and 40 mg/kg groups (P < 0.05). Dietary 40 mg/kg G. elegans alkaloids had a significant effect on the contents of LDH, AST, ALT, ALP, TG, TC, LDL-C, HDL-C, ALB and TP in M. amblycephala (P < 0.05). Fish fed 20 mg/kg and 40 mg/kg dietary G. elegans alkaloids showed significant increase in complement 3, complement 4 and immunoglobulin M contents. The liver antioxidant enzymes (SOD, CAT and T-AOC) and MDA content significantly increased at 20 mg/kg and 40 mg/kg G. elegans alkaloids supplement (P < 0.05). The mRNA levels of immune-related genes IL-1β, IL8, TNF-α and IFN-α were significantly up-regulated, whereas TGF-β and IL10 genes were significantly down-regulated in the liver, spleen and head kidney of fish fed dietary supplementation with 20 mg/kg and 40 mg/kg G. elegans alkaloids. After challenge with Aeromonas hydrophila, significant higher survival rate was observed at 20 mg/kg and 40 mg/kg G. elegans alkaloids supplement (P < 0.05). Therefore, these results indicated that M. amblycephala fed a diet supplemented with 20 mg/kg and 40 mg/kg G. elegans alkaloids could significantly promote its growth performance, lipids and amino acids deposition, immune ability and resistance to Aeromonas hydrophila.

A Laboratory Maintenance Regime for a Fungus-Growing Termite Macrotermes gilvus (Blattodea: Termitidae).

The optimum maintenance conditions of the fungus-growing termite, Macrotermes gilvus (Hagen) (Blattodea: Termitidae), in the laboratory were studied. Termites were kept on a matrix of moist sand and with fungus comb as food. The survival of groups of termites was measured when maintained at different population densities by changing group size and container volume. Larger groups (≥0.6 g) were more vigorous and had significant higher survival rates than smaller groups (≤0.3 g). The population density for optimal survival of M. gilvus is 0.0025 g per container volume (ml) or 0.0169 g per matrix volume (cm(3)), i.e., 1.2 g of termites kept in a 480-ml container filled with 71 cm3 of sand. In termite groups of smaller size (i.e., 0.3 g) or groups maintained in smaller container (i.e., 100 ml) the fungus comb was overgrown with Xylaria spp., and subsequently all termites died within the study period. The insufficient number of workers for regulating the growth of unwanted fungi other than Termitomyces spp. in the fungus comb is the most likely reason. Unlike some other mound-building termite species, M. gilvus showed satisfactory survival when maintained in non-nutritious matrix (i.e., sand). There was no significant difference in the survival rate between different colonies of M. gilvus (n=5), with survival in the range of 78.5-84.4% after 4 wk. Advances in the maintenance of Macrotermes will enable researchers to study with more biological relevance many aspects of the biology, behavior, and management of this species.

Extraction and identification of exosomes from drug-resistant breast cancer cells and their potential role in cell-to-cell drug-resistance transfer

To explore whether docetaxel-resistant cells (MCF-7/Doc) and doxorubicin-resistant cells (MCF-7/ADM) can secrete Exosomes and their potential role in cell-cell drug-resistance transfer. Exosomes were extracted from the cell culture supernatants of MCF-7/Doc and MCF-7/ADM cells by fractionation ultracentrifugation, and were identified by transmission electron microscopy and Western blot analysis. GFP-MCF-7/S, a breast cancer parental sensitive cell line stably expressing green fluorescent protein (GFP), was constructed by recombinant lentiviral vector with GFP. Then the resistance experiment of cells and the experiment of resistance transfer by exosomes were designed to observe the phenomenon of cell-to-cell drug-resistance transfer. Similar to the breast cancer parental sensitive cells (MCF-7/S), the breast cancer resistant sublines could secrete exosomes, which exhibited round or elliptic shape ranging from 30 to 100 nm in diameter with intact membrane, and only expressed the protein marker of exosomes, Tsg101, did not express the endoplasmic reticulum marker calnexin. After MCF-7/S, MCF-7/DOC and MCF-7/ADM cells we cocultured with GFP-MCF-7/S cells for 72 h, there were no significant differences in the expression of fluorescence-labeled cells among the four groups. When treated by the drug ADM or DOC for 24 hours, the MCF-7/DOC+GFP-MCF-7/S group was in favor of a significant higher survival rate of fluorescence-labeled cells compared with the MCF-7/S+GFP-MCF-7/S group (65.5% vs. 25.5%, P < 0.001), and so did the MCF-7/ADM+GFP-MCF-7/S group (53.6% vs. 25.4%, P < 0.001). The exosomes extracted from MCF-7/S, MCF-7/DOC and MCF-7/ADM cells were cultured with the GFP-MCF-7/S cells for 48 h. Among these groups, no significant differences in the expression of fluorescence-labeled cells were found. After treated by the drug ADM or DOC for 24 hours, the exosomes extracted from MCF-7/DOC+GFP-MCF-7/S group was associated with a significant higher survival rate of fluorescence-labeled cells compared with the exosomes extracted from MCF-7/S+GFP-MCF-7/S group (59.9% vs. 32.4%, P < 0.001), and so did the exosomes extracted from the MCF-7/ADM)+GFP-MCF-7/S group (58.3% vs. 27.2%, P < 0.001). Our results suggest that drug-resistance can be transferred between breast cancer cells, and exosomes are probably the transporter of the drug resistance.

Reproductive performance and offspring quality of wild-caught and pond-reared swimming crab Portunus trituberculatus broodstock

The farming of the swimming crab, Portunus trituberculatus, has expanded quickly in east China over the past decade. To date, the seed production of the crab is dependent on wild-caught broodstock, which could become a constraint to the sustainable development of this crab aquaculture. The present study was conducted to compare the reproductive performance and offspring quality of wild-caught (WC) and pond-reared (PR) P. trituberculatus. The reproductive performance, egg and larval quality of WC and PR P. trituberculatus in a same size range were assessed under identical conditions. The results showed that although no significant differences on female survival, percentage spawned and female fecundity were found between WC and PR crabs ( P > 0.05), eggs produced by WC females had significantly higher hatchability (WC = 80.72%; PR = 70.75%) as well as shorter embryonic development time ( P < 0.05). Similarly, zoea I larvae hatched from WC females had substantially larger carapace length (WC = 624.9 μm; PR = 603.3 μm) ( P < 0.05) than those from PR crabs. Furthermore, under identical culture conditions, zoea I hatched from WC females had significant higher survival rate (WC = 90.0%; PR = 72.0%) and faster development time to zoea II (WC = 3.6 days; PR = 4.3 days) than that of PR broodstock ( P < 0.05). Biochemical analysis detected significantly lower contents of cholesterol, EPA, ARA and certain essential amino acids (e.g. Phe, His and Arg) in the eggs of PR P. trituberculatus than those of WC females ( P < 0.05), indicating that these nutrients may play an important role in determining egg and larval quality of P. trituberculatus. In conclusion, our results demonstrated that although PR females produced similar quantity eggs, significantly lower egg hatchability and larval quality compared to WC females were evident. The differences in egg biochemical compositions between WC and PR crabs suggested that the offspring quality of the PR P. trituberculatus could be improved by optimizing broodstock diets.

Role of Pittsburgh Modified TNM Criteria in prognosis prediction of liver transplantation for hepatocellular carcinoma

Pittsburgh modified TNM criteria is one of the prognostic models of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). In this study, we applied this prognostic system in a series of HCC patients receiving OLT to verify its reliability in the clinical prognostic prediction. The clinical record and follow-up data of 102 patients with HCC underwent OLT was collected. The patients were classified by 3 staging systems: the Pittsburgh Modified TNM Criteria, International Union Against Cancer (UICC) pTNM Staging System, and Milan Criteria. Survival rates of the patients were analyzed using the Kaplan-Meier method and the Log-Rank test, and then the prognostic values of the 3 staging systems were compared. Among the 3 staging systems, the Pittsburgh Modified TNM Criteria showed the best stratification of patients with different prognosis. The overall survival rates of the patients at the Pittsburgh modified TNM stage I, II, III, and IV were 94.4%, 83.3%, 58.2%, and 36.8% at 1 year, and 79.4%, 62.5%, 26.2%, and 10.5% at 3 years, respectively. For those patients exceeding the Milan Criteria, the patients at Pittsburgh stages I and II had a significant higher survival rate than those at Pittsburgh stages III and IV (P < 0.001). The Pittsburgh Modified TNM Criteria is a more reliable postoperative staging system than the UICC pTNM staging system for HCC patients receiving OLT. As providing more accurate prognostic classification, it could be reasonable to combine the Milan Criteria for recipient selection.

Feasibility of Endoscopic Papillectomy in Early Stage Ampulla of Vater Cancer

Objectives: Traditional treatment for ampullary tumors was surgical procedures including pancreaticoduodenectomy (PD), pylorus-preserving PD (PPPD), and local resection of the ampulla. Endoscopic papillectomy appears to be an effective method for treating ampullary adenomas. The delicate question is about early stage ampullary adenocarcinoma (pTis, pT1). The aim of this study was to indirectly assess the factors to predict malignancy, lymph node metastasis and suggest potential indication of endoscopic papillectomy in ampulla of Vater tumor by analyzing clinicopathologic datas in patents with this disease. Method: We retrospectively evaluated clinocopathologic factors and long term outcome of 235 patients with ampullary cancer and 24 patients with ampullary adenoma diagnosed between 1991 and 2006. Results: In symptoms leading to the diagnosis for ampullary tumor, 14 (58%) of 24 patients with adenoma had no symptoms and were diagnosed incidentally during routine examinations for health checkups. Twelve of 14 patients with no symptom were diagnosed by endoscopy and the statistical difference was significant (p < 0.001). In patients with ampullary adenocarcinoma, 118 patients (50%) were presented with jaundice (p < 0.001) and 104 patients (44%) showed high bilirubin level (>3 mg/dL) (p < 0.001). Endoscopic biopsies missed malignancy in 33 cases (16%). Seventeen cases (71%) of 24 adenomas with high grade and 9 cases (75%) of 12 adenoma with atypism in endoscopic biopsy specimen were adenocarcinomas, whereas two cases (15%) of 13 adenomas with low grade was adenocarcinomas. Tumor size, histologic grade, depth of invasion, common bile duct invasion, angiolymphatic invasion and venous invasion were significantly related with lymph-node metastasis. Early stage ampullary adenocarcinoma less than 2 cm in size and a well-differentiated histology (n = 17) showed no lymph node metastasis and no recurrence during the median follow up period of 35.9 months. Patients with early stage ampullary adenocarcinoma had a significant higher survival rate, compared to pT2 or pT3 stage adenocarcinoma (P = 0.002 and p < 0.001, respectively). The overall 5 year survival rates of early stage, pT2 and pT3 stages adenocarcinomas was 88%, 65% and 56% resepectively. Conclusion: Endoscopic papillectomy can be applied as a viable alternative to surgery in patients with early stage ampullary adenocarcinoma less than 2 cm in size and a well-differentiated histology. When the resected specimen showed a well-differentiated histology, no resection margin involvement, and no angiolymphatic invasion, the subsequent radical surgery is not needed.

Analyse der Todesursachen von ICD-Patienten in der Langzeitbeobachtung

Implantable cardioverter defibrillators represent an effective therapy to prevent sudden cardiac death in patients with ventricular arrhythmias. This implies a change in the spectrum of causes of death. There exist no large studies providing an exact differentiation of these causes of death. During a mean observation period of 41+/-29 months (3 d-12 yrs), we analyzed the outcome of 429 ICD patients (CAD n=274, dilative CMP n=97, others n=23, no structural heart disease n=35), mean age 62+/-12 years (23-87 yrs). The overall survival rate was 79.7% whereby 3.5% of these patients underwent successful heart transplantation and 2.1% died suddenly. 60.9% of all deaths showed a non-sudden cardiac cause (heart failure 56.3%, myocardial infarction 4.6%). In 28.7% a non-cardiac fatal event was present (cancer 11.5%, septicemia 6.9%, stroke 4.6%). The deceased showed significantly more often structural heart disease (100 vs 92%, p<0.02) and a lower left ventricular ejection fraction (37+/-14 vs 44+/-18%, p<0.02). Significant higher survival rates were associated with medication with beta blockers (88 vs 75%, p<0.02) and the class III antiarrhythmic agents sotalol und amiodarone (85 vs 77%, p<0.03). Mortality due to sudden death was reduced to 2.1% in ICD patients associated with a shift of causes of death towards severe heart failure. Therefore, special attention should be paid to the signs of heart failure in these patients to enable early initiation of appropriate therapeutic strategies.

11C-Methionine positron emission tomography as an early predictor of outcome in bone and soft tissue sarcomas treated by carbon ion radiotherapy

3098 Background: The development of the novel carbon ion radiotherapy (CIRT) in the treatment of refractory cancers has resulted in the need for a way to accurately evaluate patients' prognosis. Amino acid metabolism of cancer is associated with numerous catabolic processes favoring tumor growth. As an essential amino acid, L-methionine plays a central role in the altered metabolism of cancer cells. We initially evaluated whether MET uptake and its change measured by PET after carbon ion radiotherapy were the early survival predicators in patients with bone and soft tissue sarcomas. Methods: MET PET was prospectively performed in 62 patients with bone and soft tissue sarcomas before and within one month after CIRT. Tumor MET uptake was measured with the semiquantitative tumor-to-nontumor ratio (T/N ratio). The MET uptake in the tumor and relevant clinical parameters were entered into univariate and multivariate survival analysis. Results: The overall median survival time was 20 months. Patients with a baseline T/N ratio of ≤ 6 had a significant better survival than patients with a baseline T/N ratio > 6 (2-year survival rate: 69.4% versus 32.3%, P=0.01). Patients with a post CIRT ratio of ≤ 4.4 had a better survival than that with a post CIRT ratio > 4.4 (2-year survival rate: 63.7% versus 41.3%, P=0.01). A significant higher survival rate was observed in patients with posttherapeutic MET uptake change of > 30% than patients in lower change group (2-year survival rate: 74.6% versus 41.6%, P=0.049). The multivariate analysis showed that both baseline and postCIRT T/N ratio were statistically significant independent predictors of patient survival. Tumors with larger T/N ratio had a significantly poorer prognosis. Conclusions: MET uptake, as measured by either baseline or postCIRT T/N ratio was an independent predictor of survival in patients with bone and soft tissue sarcomas treated by CIRT, while posttherapeutic MET uptake change might have potential value for the same purpose. No significant financial relationships to disclose.

The Prognosis and Survival of Childhood Acute Lymphoblastic Leukemia with Central Nervous System Relapse

Central nervous system (CNS) relapse in childhood acute lymphoblastic leukemia (ALL) has been overcome by sensitive therapatic approachs. This study was planned to present the development of CNS relapse and survival in newly diagnosed 190 ALL patients whose cases were followed in the authors' unit between March 1991 and May 2002. St. Jude Study XI protocol was given to the patients who applied between March 1991 and March 1997 (group A) (n = 122), and St. Jude Study XIII protocol was given to the patients who applied between March 1997 and May 2002 (group B) (n = 68). The patients having isolated CNS relapse in group A received craniospinal irradiation (CSI) median 3.5 months after CNS relapse (range 2–6 months), a short time after reinduction, and 2 cures of consolidation. In group B, patients having isolated CNS relapse received IT once a month and a high-dose methotrexate treatment once every 8 weeks and 3 or 4, cures later therapy CSI median 7 months after CNS relapse (range 6–8 months) was given. When the overall survival rates of the 2 groups are compared, a statistically significant higher survival rate at 5 years was determined in group B than in group A (respectively, 82.3%, 58.4%) (p < .05). When subgroups of the patients (that is, those with no relapse, isolated CNS or BM relapse, or CNS + BM relapse) were compared in both groups, it was found that survival was much higher for the ones with no relapse and with isolated CNS relapse (respectively, 87.9%, 72.7%) compared to isolated BM or CNS + BM relapse groups (respectively, 10%, 13.3%) (p < .05). In a conclusion, for children with acute lymphoblastic leukemia and an isolated CNS relapse, with delayed definitive craniospinal irradiation allowing more intensive systemic and intrathecal chemotherapy results in better overall survival than has been previously reported.