Laparoscopic versus open total gastrectomy for T4a gastric cancer: a propensity score-matched analysis of long-term outcomes.

Evidence of implementation of laparoscopic total gastrectomy (LTG) for surgical T4a stage (sT4a) gastric cancer (GC) remains inadequate. This study aimed to compare short- and long-term outcomes of LTG versus open total gastrectomy (OTG) for sT4a GC. This retrospective cohort study was conducted using data from patients with sT4a GC underwent total gastrectomy from 2014 to 2020. Short-term outcomes included operative characteristics and postoperative complications. Long-term oncological outcomes focused on 3-, and 5-year overall survival (OS) and disease-free survival (DFS). Propensity score matching (PSM) was applied to reduce potential biases in baseline characteristics between groups. There was a total of 161 patients, in which 96 underwent LTG and 65 underwent OTG. After PSM, both groups consisted of 51 patients each, with balanced baseline characteristics. There were no significant differences between the two groups regarding blood loss, length of proximal resected margin, postoperative hospital stays, and overall and major postoperative complications. Most of the complications were classified as minor according to the Clavien-Dindo classification. Operating time was significantly longer in the LTG group (mean: 257 min vs. 231 min, p = 0.006). LTG was superior to OTG groups in time to flatus (mean: 3.0 days vs 3.9 days, p < 0.001). Five-year OS and DFS rates were similar between the two groups (44% and 33% vs. 43% and 28% in the LTG and OTG groups, respectively). Our findings indicate that LTG is a feasible and safe technique, exhibiting comparable long-term oncological outcomes to OTG for sT4a GC. LTG may be an acceptable alternative to OTG for the treatment of sT4a GC.

Challenges in the Assessment of Medullary Bone Invasion in Oral Cavity Cancers and Its Prognostic Significance.

BACKGROUND: As per AJCC 8th edition TNM staging system, bone invasion is a poor prognostic marker that upstages oral cavity squamous carcinoma (OSCC) to pT4a. Cortical erosion alone of bone or tooth socket by a gingival primary is not sufficient to upstage a tumour. The differentiation of cortical erosion from invasion through the cortical bone into the medulla is often challenging, limiting accurate staging. This review aims to assess the difficulties in differentiating cortical erosion from medullary invasion and evaluate the prognostic significance of different patterns of bone involvement. METHODS: A retrospective review of OSCC with primary curative surgery and bone resection treated at a single-center over 10 years, was performed to assess the prognostic significance of bone invasion. Hematoxylin-eosin stained slides of a subset of cases were re-reviewed in a planned manner to assess difficulties in precise categorization (no invasion/erosion/cortical invasion and medullary invasion), evaluate interobserver agreement, and correlate with clinical outcome. RESULTS: Five hundred and ninety patients were included, with a median follow-up of 28 months. On univariate analysis, the 3-year local, nodal and distant metastasis control were not significantly different in the 3 groups of no invasion, erosion, and invasion (p = 0.43, 0.47, and 0.47, respectively). Overall survival (OS) at 3 years was 78.1% and disease-free-survival(DFS) was 63.7% in the entire cohort. On univariate analysis, there was significant difference in OS and DFS based on these groups. This did not translate into independent prognostic benefit on multivariable analysis (p = 0.75 and 0.19, respectively). The independent prognostic factors were margin positivity, tumor differentiation, perineural invasion and pathological nodal involvement. Planned re-review of a subset of 202 cases resulted in a change in bone involvement category in 26/202 cases, which was mainly due to difficulty in assessing cortico-medullary junction near the tooth socket and bone fragmentation. The assessment showed moderate to near complete agreement (kappa 0.59-0.82) between 2 observers. CONCLUSION: Our study shows that bone involvement is not an independent prognostic marker and there is no specific correlation of medullary invasion with outcome over those that showed cortical erosion. Several factors contribute to difficulties and interobserver variability in assessing bone involvement.

Overcoming fear of developing country: A case report of retroperitoneal laparoscopic partial nephrectomy for T3A renal cell carcinoma.

INTRODUCTION: Renal cell carcinoma poses significant challenges in kidney diseases, particularly in the context of the T3 stage, where treatment strategies remain controversial. The utilization of laparoscopic partial nephrectomy, particularly in developing countries, has been restricted for such patients, primarily due to limited infrastructure and concerns about recurrence risk and long-term pathologic outcomes. PRESENTATION OF CASE: In this report, we present a case of a 64-year-old male diagnosed with T3aN0M0 renal cell carcinoma (RCC). Abdominal computed tomography revealed a 5.2 × 5.2 × 5.1 cm mass on the right upper part of the kidney with a possible thrombus in the superior renal polar vein. The patient underwent successful treatment with retroperitoneal laparoscopic partial nephrectomy (LPN), leading to the preservation of kidney function with <4 mL/min/1.73 m2 GFR reduced after one year postoperative (estimated GFR from 85 mL/min/1.73 m2 to 81.79 mL/min/1.73 m2). The patient was discharged after three days; no recurrence was observed during the follow-up. DISCUSSION: For stage T3a RCC, studies show that LPN induces comparable long-term outcomes to radical nephrectomy, with advantages such as preserved kidney function, reduced operative time, blood loss, and shorter hospital stays. However, due to infrastructure constraints and limited access to robotic-assisted surgery in our country, coupled with concerns about tumor recurrence, laparoscopic radical nephrectomy is predominantly employed for similar patients. Our case represents one of the very first cases in which we successfully treated a patient diagnosed with T3a RCC using retroperitoneal laparoscopic partial nephrectomy. CONCLUSION: Laparoscopic partial nephrectomy is a reliable choice for T3aN0M0 RCC with good long-term outcomes and preserved renal function, especially by the hands of an experienced laparoscopic surgeon.

Adverse pathologic features impact survival outcomes for small renal masses following nephrectomy.

PURPOSE: While most small renal masses (SRM) < 4 cm have an excellent prognosis following resection, the impact of adverse T3a pathologic features on oncologic outcomes of SRMs remains unclear. We sought to compare clinical outcomes for surgically resected pT3a versus pT1a SRMs at our institution. MATERIALS AND METHODS: We retrospectively reviewed records of patients who underwent radical or partial nephrectomy (RN, PN) for renal tumors <4 cm at our institution between 2010 and 2020. We compared features and outcomes of pT3a vs pT1a SRMs. Continuous and categorical variables were compared using Student's t and Pearson's chi-squared tests, respectively. Postoperative outcomes of interest including overall, cancer-specific, and recurrence-free survival (OS, CSS, and RFS) were analyzed using Kaplan-Meier method, Cox proportional hazard regression, and competing risk analysis. Analyses were performed using R statistical package (R Foundation, v4.0). RESULTS: We identified 1,837 patients with malignant SRMs. Predictors of postoperative pT3a upstaging included higher renal score, larger tumor size, and presence of radiologic features concerning for T3a disease (odds ratio [OR] = 5.45, 95% confidence interval [CI] 3.92-7.59, P < 0.001). On univariable modeling, pT3a SRMs had higher positive margin rates (9.6% vs 4.1%, P < 0.001), worse OS (hazard ratio [HR] = 2.9, 95% CI 1.6-5.3, P = 0.002), RFS (HR 9.32, 95% CI 2-40.1, P = 0.003), and CSS (HR = 3.6, 95% CI 1.5-8.2, P = 0.003). On multivariable modeling, pT3a status remained associated with worse RFS (HR = 2.7, 95% CI 1.04-7, P = 0.04), but not OS (HR 1.6, 95% CI = 0.83-3.1, P = 0.2); multivariable modeling was deferred for CSS due to low event rates. CONCLUSIONS: Adverse T3a pathologic features portend worse outcomes for SRMs, highlighting the crucial role of pre-operative planning and case selection. These patients have relatively poor prognosis, and should be monitored more closely and counseled for consideration of adjuvant therapy or clinical trials.

Impact of primary treatment methods on sludge characteristics and digestibility, and wastewater treatment plant-wide economics.

Biogas production from anaerobic sludge digestion plays a central role for wastewater treatment plants to become more energy-efficient or even energy-neutral. Dedicated configurations have been developed to maximize the diversion of soluble and suspended organic matter to sludge streams for energy production through anaerobic digestion, such as A-stage treatment or chemically enhanced primary treatment (CEPT) instead of primary clarifiers. Still, it remains to be investigated to what extent these different treatment steps affect the sludge characteristics and digestibility, which may also impact the economic feasibility of the integrated systems. In this study, a detailed characterization has been performed for sludge obtained from primary clarification (primary sludge), A-stage treatment (A-sludge) and CEPT. The characteristics of all sludges differed significantly from each other. The organic compounds in primary sludge consisted mainly of 40% of carbohydrates, 23% of lipids, and 21% of proteins. A-sludge was characterized by a high amount of proteins (40%) and a moderate amount of carbohydrates (23%), and lipids (16%), while in CEPT sludge, organic compounds were mainly 26% of proteins, 18% of carbohydrates, 18% of lignin, and 12% of lipids. The highest methane yield was obtained from anaerobic digestion of primary sludge (347 ± 16 mL CH4/g VS) and A-sludge (333 ± 6 mL CH4/g VS), while it was lower for CEPT sludge (245 ± 5 mL CH4/g VS). Furthermore, an economic evaluation has been carried out for the three systems, considering energy consumption and recovery, as well as effluent quality and chemical costs. Energy consumption of A-stage was the highest among the three configurations due to aeration energy demand, while CEPT had the highest operational costs due to chemical use. Energy surplus was the highest by the use of CEPT, resulting from the highest fraction of recovered organic matter. By considering the effluent quality of the three systems, CEPT had the highest benefits, followed by A-stage. Integration of CEPT or A-stage, instead of primary clarification in existing wastewater treatment plants, would potentially improve the effluent quality and energy recovery.

Comparison of Long-term Outcomes for Young and Healthy Patients with cT1a and cT3a Renal Cell Carcinoma Treated with Partial Nephrectomy.

Partial nephrectomy (PN) is recommended for renal cell carcinoma (RCC) of <4 cm. We hypothesized that there is no difference in all-cause mortality (ACM) between cT1a, cT1b, and cT3a <4 cm RCC following PN. The National Cancer Database was interrogated to identify patients aged <60 yr with a Charlson comorbidity index ≤1 diagnosed between 2004 and 2017. Cox proportional-hazard models stratified for cT stage were used to predict 10-yr ACM. A total of 30 195 patients (25 121 cT1a, 4884 cT1b, and 190 cT3a <4 cm) who underwent PN with median follow-up of 64.36 mo (interquartile range 42.91-93.77) were included. Cox analysis revealed no significant difference in 10-yr ACM between cT1a and cT3a <4 cm (hazard ratio [HR] 1.05, 95% confidence interval [CI] 0.58-1.90; p = 0.88). However, the cT1b group had higher ACM (HR 1.31, 95% CI 1.15-1.48; p < 0.01). The positive surgical margin (PSM) rate was higher for cT3a <4 cm than for cT1a tumors (14.2% vs 6.3%; p < 0.01). However, there was no difference in 10-yr ACM rate between cT1a and cT3a <4 cm (10.9% vs 9.7%; p = 0.42). Our results suggest that PN is an option for cT3a RCC <4 cm, particularly in cases in which maximum nephron preservation is essential, such as patients with chronic kidney disease or a solitary kidney, although a higher PSM risk should be appreciated. PATIENT SUMMARY: We found that partial removal of the kidney for localized advanced kidney cancer is safe. The rate of surgical margins positive for the presence of tumor is higher in localized advanced kidney cancer than for less advanced cancers, but there was no difference in 10-year predicted mortality.

Exploring the stability of an A-stage-EBPR system for simultaneous biological removal of organic matter and phosphorus.

This work evaluates the performance and stability of a continuous anaerobic/aerobic A-stage system with integrated enhanced biological phosphorus removal (A-stage-EBPR) under different operational conditions. Dissolved oxygen (DO) in the aerobic reactor was tested in the 0.2-2 mgDO/L range using real wastewater amended with propionic acid, obtaining almost full simultaneous COD and P removal without nitrification in the range 0.5-1 mgDO/L, but failing at 0.2 mgDO/L. Anaerobic purge was tested to evaluate a possible mainstream P-recovery strategy, generating a P-enriched stream containing 22% of influent P. COD and N mass balances indicated that about 43% of the influent COD could be redirected to the anaerobic digestion for methane production and 66% of influent NH4+-N was discharged in the effluent for the following N-removal B-stage. Finally, when the system was switched to glutamate as sole carbon source, successful EBPR activity and COD removal were maintained for two months, but after this period settleability problems appeared with biomass loss. Microbial community analysis indicated that Propionivibrio, Thiothrix and Lewinella were the most abundant species when propionic acid was the carbon source and Propionivibrio was the most favoured with glutamate. Thiothrix, Hydrogenophaga, Dechloromonas and Desulfobacter appeared as the dominant polyphosphate-accumulating organisms (PAOs) under different operation stages.

Association of Extrarenal Invasion Patterns and Tumor Size with the Differences in Survival Outcomes of T3a Renal Cell Carcinoma: A Proposal Modified T3a Stage System is Needed.

OBJECTIVE: T3a renal cell carcinoma (RCC) did not consider tumor size and different extrarenal invasion patterns in the current TNM staging system. Here, we want to investigate the association of survival outcomes with different extrarenal invasion patterns and tumor size of T3a RCC. METHODS: We identified T3a RCC patients from the Surveillance, Epidemiology, and End Results database in 2004-2015. The extrarenal invasion patterns included renal vein invasion, renal sinus/peri-sinus fat invasion, or perinephric fat invasion. Cox proportional hazards models and Fine and Gray models were used to estimate overall survival (OS) and cancer-specific survival (CSS), and the hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. C-index is used to evaluate the predictive ability of the model. Restricted cubic splines were used to estimate the HRs of tumor size on the risk of OS and CSS. RESULTS: In total, 4834 T3a RCC patients were included in the analysis. Of them, 1403 (29%) present isolated extrarenal invasion pattern, while 1403 (71%) were any combined invasion pattern, which was associated with a higher risk of lymph-node/distant metastasis and a worse OS and CSS compared with isolated extrarenal invasion pattern, but a comparable CSS and OS were observed between each isolated invasion pattern. In restricted cubic splines, a non-linear shape was observed for the association between the tumor size and OS and CSS, compared with the smallest tumor size group (≤4cm), the adjusted HR of the largest tumor size group (≥10cm) was 1.59 for all-cause mortality, and 2.27 for tumor-specific mortality, respectively. However, in a cohort of T3a RCC with a combined invasion pattern, tumor size is not an independent risk factor for prognosis. Finally, the model added two covariates of tumor size and invasion patterns that could improve the predictive ability of OS and CSS for T3a patients (c-index: +1.2%, +1.3%, respectively). CONCLUSION: Tumor size and extrarenal invasion type are valid parameters of the OS and CSS for T3a RCC patients and need to be considered for the next generation of the T-stage system.

The prognostic value of fat invasion and tumor expansion in the hilar veins in pT3a renal cell carcinoma.

PURPOSE: The 7th TNM classification summarizes renal cell carcinoma (RCC) with perirenal (PFI) and/or sinus fat invasion (SFI) as well as hilar vein involvement (RVI) as pT3a tumors. In this study, we aimed to determine the prognostic value of fat invasion (FI) in the different compartments and RVI for medium-term cancer-specific-survival (CSS) in pT3a RCC. MATERIALS AND METHODS: Patients with pT3a RCC were identified using an institutional database. All original pathological reports were reclassified according to the 7th TNM edition. The prognostic value of FI as well as divided into PFI, SFI, combined PFI + SFI, and RVI for CSS was assessed using univariate and multivariate Cox-regression analysis. Survival was estimated using the Kaplan-Meier method. RESULTS: Median follow-up in 184 pT3a tumors was 38 months. FI was detectable in 153 patients (32.7% PFI, 45.1% SFI, 22.2% PFI + SFI), 31 patients showed RVI alone. Combined PFI + SFI increased the risk of cancer-related death compared to PFI (HR 3.11, p < 0.01), SFI (HR 1.84, p = 0.023) or sole RVI (HR 2.12, p = 0.025). In multivariate analysis, a combined PFI + SFI vs. PFI or SFI as the only compartment involved was confirmed as independent prognostic factor (HR 1.83, p = 0.029). Patients with FI and simultaneous RVI had significantly shorter CSS (HR 2.63, p < 0.01). In an unweighted model, the difference between patients with combined PFI + SFI and RVI and those with PFI alone was highest (HR 4.01, p = 0.029). CONCLUSIONS: These results underline the subdivision of pT3a RCC depending on the location of FI and RVI for patient stratification.

Outcomes of Robot-assisted Partial Nephrectomy for Clinical T3a Renal Masses: A Multicenter Analysis.

BACKGROUND: Use of partial nephrectomy (PN) in T3 renal cell carcinoma (RCC) is controversial. OBJECTIVE: To evaluate quality outcomes of robot-assisted PN (RAPN) for clinical T3a renal masses (cT3aRM). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective multicenter analysis of patients with cT3aN0M0 RCC who underwent RAPN. INTERVENTION: RAPN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was a trifecta composite outcome of negative surgical margins, warm ischemia time (WIT) ≤25 min, and no perioperative complications. The optimal outcome was defined as achieving this trifecta and ≥90% preservation of the estimated glomerular filtration rate (eGFR) and no stage upgrading of chronic kidney disease. Multivariable analysis (MVA) identified risk factors associated with lack of the optimal outcome. Kaplan-Meier analysis was conducted for survival outcomes. RESULTS AND LIMITATIONS: Analysis was conducted for 157 patients (median follow-up 26 mo). The median tumor size was 7.0 cm (interquartile range [IQR] 5.0-7.8) and the median RENAL score was 9 (IQR 8-10). Median estimated blood loss (EBL) was 242 ml (IQR 121-354) and the median WIT was 19 min (IQR 15-25). A total of 150 patients (95.5%) had negative margins. Complications were noted in 25 patients (15.9%), with 4.5% having Clavien grade 3-5 complications. The median change in eGFR was 7 ml/min/1.72 m2, with ≥90% eGFR preservation in 55.4%. The trifecta outcome was achieved for 64.3% and the optimal outcome for 37.6% of the patients. MVA revealed that greater age (odds ratio [OR] 1.06; p = 0.002), increasing RENAL score (OR 1.30; p = 0.035), and EBL >300 ml (OR 5.96, p = 0.006) were predictive of failure to achieve optimal outcome. The 5-yr recurrence-free survival, cancer-specific survival, and overall survival, were 82.1%, 93.3%, and 91.3%, respectively. Limitations include the retrospective design. CONCLUSIONS: RAPN for select cT3a renal masses is feasible and safe, with acceptable quality outcomes. Further investigation is requisite to delineate the role of RAPN in cT3a RCC. PATIENT SUMMARY: Robot-assisted partial nephrectomy in patients with stage 3a kidney cancer provided acceptable survival, functional, and morbidity outcomes in the hands of experienced surgeons, and may be considered as an option when clinically indicated.

Predictive and prognostic significance of M descriptors of the 8th TNM classification for advanced NSCLC patients treated with immune checkpoint inhibitors.

BACKGROUND: A strong association between M descriptors and prognosis of non-small cell lung cancer (NSCLC) has been demonstrated recently. However, its predictive and prognostic significance for advanced NSCLC patients treated with immune checkpoint inhibitors (ICIs) remain unclear. In this study, we aimed at investigating the impact of M descriptors on clinical outcomes in those patients. METHODS: A retrospective analysis was conducted. Patients treated with more than two cycles of ICIs were included. Detailed characteristics and clinical response after immunotherapy were recorded. M descriptors were classified into M1a, M1b, and M1c according to the 8th TNM classification. RESULTS: A total of 103 patients were enrolled, including 42 with M1a disease, 16 with M1b disease and 45 with M1c disease. Patients with M1a disease demonstrated significant longer median progress-free survival (PFS) (11.9 vs. 4.1 and 3.2 months, respectively, P=0.0002) and overall survival (OS) (35 vs. 22.1 and 12 months, P=0.02) than those with M1b and M1c disease. Patients with M1a disease showed higher objective response rate (ORR) (28.6% vs. 14.8%, P=0.08) and disease control rate (DCR) (81% vs. 59%, P=0.02) compared with those with M1b and M1c disease. Multivariate analysis identified M1a stage as being independently associated with prolonged PFS and had better OS than those with M1c disease (P=0.05) but not M1b disease (P=0.06). CONCLUSIONS: The current study demonstrated a clear association between M descriptors and the therapeutic response to ICIs and confirmed its prognostic role in advanced patients treated with ICIs monotherapy. M descriptors may need to be stratified in future study design.

Living on the edge: Prospects for enhanced biological phosphorus removal at low sludge retention time under different temperature scenarios.

The design of new wastewater treatment plants with the aim of capturing organic matter for energy recovery is a current focus of research. Operating with low sludge residence time (SRT) appears to be a key factor in maximizing organic matter recovery. In these new configurations, it is assumed that phosphorus is chemically removed in a tertiary step, but the integration of enhanced biological phosphorus removal (EBPR) into these short-SRT systems seems to be an alternative worth studying. A key point of this integration is to prevent the washout of polyphosphate accumulating organisms (PAO) despite the low SRT applied. However, the minimum SRT required to avoid PAO washout depends on temperature, due to its effects on reaction kinetics, gas transfer rates, biomass growth and decay rates. This work includes a wide range of short and long-term experiments to understand these interactions and shows which combinations of SRT and temperature are detrimental to PAO growth. For example, an EBPR system operating at 20 °C and SRT = 5 d showed good performance, but EBPR activity was lost at 10 °C. EBPR operated at SRT = 10 d had 86% P removal at 20 °C but decreased to 71% at 15 °C and progressively lost its activity at lower temperature. The temperature coefficient obtained for PAO show a low degree of temperature dependence (θ = 1.047 ± 0.014), and should be considered when designing short-SRT systems with EBPR.

Prognostic value of perirenal and/or sinus fat infiltration in patients with pT3a renal cell carcinoma: A multicentre cohort study. LARCG Group. / Valor pronóstico de la invasión de grasa perirrenal y/o del seno en pacientes con carcinoma de células renales pT3a: estudio de cohorte multicéntrico. Grupo LARCG.

INTRODUCTION AND OBJECTIVES: The objective of this study is to evaluate overall survival (OS), cancer-specific survival (CSS), relapse-free survival, local and distant (LRFS and DRFS, respectively) rates in patients with pT3a renal cell carcinoma (RCC) considering the perirenal and/or sinus fat infiltration (FI) as prognostic factors. MATERIALS AND METHODS: Retrospective cohort of patients with pT3a RCC who underwent radical or partial nephrectomy. The data were extracted from the LARCG (Latin American Renal Cancer Group) database. The demographic, clinical, pathological and surgical variables were evaluated. FI was divided into 4 groups (vein, perirenal, sinus and both fats infiltration). The Kaplan Meier and Cox regression curves were performed. RESULTS: 293 patients were included in the study. The mean age was 61.4 years. The median follow-up was 21 months (r: 1-194). CSS, RFS, LRFS and DRFS estimated at 3 years in the group of both fats' infiltration were 53.1, 45.1, 58.7 and 51.6 months, respectively, and always statistically lower than the rest (P˂0.005). In the multivariate analysis, the infiltration of both fats significantly increased specific mortality, overall and local relapse with respect to vein infiltration (HR: 4.5, 2.42 and 8.08, respectively). The Fuhrman grade and renal pelvis infiltration were independent predictors of CSS and RFS. CONCLUSIONS: Infiltration of both fats increases the risk of overall and local relapse in pT3a RCC. In the same way, it is associated with a lower cancer-specific survival and should be considered as a factor of poor prognosis.

Enhanced Biological Phosphorus Removal at low Sludge Retention Time in view of its integration in A-stage systems.

The two-stage A/B WWTP configuration is being studied as a possible wastewater treatment with low energy consumption or even with a net energy generation. The first phase, A-stage, is designed to remove organic matter at very short Sludge Retention Time (SRT), while the B-stage is based on autotrophic nitrogen removal. However, P-removal in the A/B process usually only relies on precipitation. This work studies the potential inclusion of Enhanced Biological Phosphorus Removal (EBPR) in the A-stage phase. For this aim, the long-term operation of three different Sequencing Batch Reactors (SBR) enriched in Accumulibacter at low SRT was thoroughly monitored for more than three months each one. This work shows that EBPR can be sustained with a minimal SRT of 3.6 d at 25 °C. Lower values, SRT = 3 d, led to the PAO washout because of a reduction in P-release and P-uptake, an increase of the VSS/TSS ratio and a decrease of the P/C ratio. The Yobs could be related to the SRT with the parameters Y = 0.39 ± 0.05 gCODX·g-1CODS and kD = 0.06 ± 0.04 d-1 which leads to a 24% increase of biomass yield when SRT was reduced from 10 to 4 d.

Clinical relevance of hypogammaglobulinemia, clinical and biologic variables on the infection risk and outcome of patients with stage A chronic lymphocytic leukemia.

The prognostic effect of hypogammaglobulinemia (HGG), clinical and biologic characteristics on the infection risk and outcome has been retrospectively analyzed in 899 patients with stage A chronic lymphocytic leukemia (CLL). Low levels of IgG were recorded in 19.9% of patients at presentation, low levels of IgM and/or IgA in 10.4% and an additional 20% of patients developed HGG during the course of the disease. Before the start of any treatment, 160 (12.9%) patients experienced at least one grade ≥3 infection requiring a systemic anti-infective treatment and/or hospitalization. While IgG levels at diagnosis were not associated with an increased risk of grade ≥3 infection or with an adverse outcome, a significantly increased rate of grade ≥3 infections was recorded in patients with unmutated IGHV (p=0.011) and unfavorable FISH aberrations (p=0.009). Late onset HGG, more frequently recorded in patients with Rai stage I-II (p=0.001) and unmutated IGHV (p=0.001), was also associated with a higher rate of severe infections (p=0.002). These data indicate that, stage A patients with clinical and biologic characteristics of a more aggressive disease develop more frequently late onset HGG, grade ≥3 infections and require a closer clinical monitoring.

Accuracy of glomerular filtration rate equations for chronic kidney disease patients at the G3a stage: a single-center cross-sectional study.

BACKGROUND: Kidney disease improving global outcomes provided a new classification for chronic kidney disease (CKD) by subdividing the G3 stage into G3a and G3b stages based on glomerular filtration rate (GFR) in 2012. Currently, a few methods are used to evaluate GFR, including measured GFR (mGFR) and estimated GFR (eGFR). One of the mGFR was 99mTc-DTPA scintigraphy method and eGFR using GFR equations were used clinically. Equations were modification of diet in renal disease (MDRD), chronic kidney disease epidemiology collaboration (CKD-EPI), and Chinese adapted MDRD (C-MDRD). This study assessed the accuracy of three different equations for estimated glomerular filtration rate (eGFR) with mGFR using DTPA scintigraphy method as the standard in a population of Chinese chronic kidney disease patients at the G3a stage. RESULTS: One hundred and twenty-two patients (age 52.0 ± 15.6 years, 69 were male) were determined as CKD stage 3 based on mGFR. Patients were divided into G3a (47 patients) and G3b (75 patients) subgroups. Bias between eGFR for CKD-EPI and reference mGFR was 0.92 mL/min and 95% limits of agreement was -38.82 to 40.67 mL/min. Bias between eGFR for C-MDRD and mGFR was 3.76 and 95% limits of agreement was -39.32 to 46.85 mL/min. Bias between eGFR for MDRD and mGFR was 3.53 and 95% limits of agreement was -43.35 to 50.4 mL/min. The CKD-EPI equation showed better diagnostic value with a greater area under the receiver operating characteristic curve (AUC: 0.763). AUC for MDRD and C-MDRD were 0.75 and 0.757, respectively. CONCLUSIONS: There were no obvious advantages in accuracy, sensitivity, and specificity for the diagnosis of patients at the G3a stage using the CKD-EPI equation.

Microarray gene expression profiling and analysis of bladder cancer supports the sub-classification of T1 tumours into T1a and T1b stages.

OBJECTIVE: To try and identify a molecular signature for pathological staging and/or grading. through microarray analysis. PATIENTS AND METHODS: We performed a prospective multicentre study between September 2007 and May 2008 that included 108 bladder tumours (45 pTa, 35 pT1 and 28>pT1). Microarray analysis was performed using Agilent Technologies Human Whole Genome 4 × 44K oligonucleotide microarrays (Agilent, Santa Clara, CA, USA). A 'dual colour' method was used vs a reference pool of tumours. From the lists of genes provided by the Biometric Research Branch class comparison analyses, we validated the microarray results of 38 selected differentially expressed genes using reverse transcriptase quantitative PCR in another bladder tumour cohort (n = 95). RESULTS: The cluster 'superficial vs invasive stage' correctly classified 92.9% of invasive stages and 66.3% of superficial stages. Among the superficial tumours, the cluster analysis showed that pT1b tumours were closer to invasive stages than pT1a tumours. We also found molecular differences between low and high grade superficial tumours, but these differences were less well defined than the difference observed for staging. CONCLUSIONS: We confirmed that the histopathological classification into subgroups pTa, pT1a and pT1b can be translated into a molecular signature with a continuous progression of deregulation (overexpression or repression of these genes) from superficial (pTa) to more invasive (pT1a then b) stages.

Prognostic factors in CLL.

Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease, as some patients progress rapidly toward the more advanced studies, whereas others survive for a long period without the need for treatment. This heterogeneity of clinical course was somehow unexplained until studies on the CLL cell features disclosed that the CLL clones were heterogeneous and were characterized by different phenotypic and genotypic features in the different patients. On the basis of these observations, it was determined in retrospective studies that clones characterized by unmutated IGHV genes, and/or CD38 and/or ZAP-70 expression conferred a more severe prognosis to the CLL patients. Here, we present data on prospective studies carried out on Binet A-stage patients, in whom the markers were determined at diagnosis and their predictive value was assessed in comparison with chromosomal abnormalities and gene expression or micro RNA profiles. In addition, hypothesis on the potential pathogenetic role of these markers will be presented.