High rates of advanced disease,complications, and decline of renal function after radical nephroureterectomy

ObjectivesRecurrences remain common following radical nephroureterectomy (RNU) for locally advanced upper-tract urothelial carcinoma (UTUC). We review a cohort of RNU patients to identify the incidence of locally advanced disease, decline in renal function, complications, and utilization of adjuvant chemotherapy (AC).MethodsInstitutional databases from 7 academic medical centers identified 414 RNU patients treated between 2003 and 2012 who had not received neoadjuvant chemotherapy. Glomerular filtration rate was estimated using the Modification of Diet in Renal Disease equation. Complications were classified according to the modified Clavien system. Cox proportional hazard modeling and Kaplan-Meier analysis determined factors associated with cancer-specific survival.ResultsOf 414 patients, 177 (43%) had locally advanced disease, including 118 pT3N0/Nx, 13 pT4N0/Nx, and 46 pTanyN+. Estimated 3- and 5-year cancer-specific survival was 47% and 34%, respectively. Only 31% of patients with locally advanced UTUC received AC. Mean estimated glomerular filtration rate declined from 59 to 51 ml/min/1.73 m² following RNU, including a new-onset decline below 60 and 45 ml/min/1.73 m² in 25% and 15% of patients, respectively (P<0.001 for both). Complications occurred in 46 of 177 (26%) patients, of which one-quarter were grade III or IV. Increasing age (Hazard Ratio (HR) 1.4, P = 0.03), positive surgical margins (HR 2.1, P = 0.01), and positive lymph nodes (HR 4.3, P<0.001) were associated with an increased risk of death from UTUC, whereas receipt of AC (HR 0.85, P = 0.05) was associated with a decrease in UTUC mortality.ConclusionsUnder one-third of RNU patients with locally advanced UTUC cancers received AC. Perioperative complications and decline in renal function may have contributed to this low rate. Such data further underscore the need for continued discussion regarding the use of chemotherapy in a neoadjuvant setting for appropriately selected patients with UTUC.     

Mesoporous superacid catalysts for valorisation of refinery naphtha stream

In the current petroleum refining scenario, many refineries end up with surplus naphtha which is either absorbed into the gasoline pool or exported at unattractive prices. Therefore, several options for naphtha valorisation are currently being explored. The usage of Liquified Petroleum Gas (LPG) as a fuel in heating appliances, cooking equipment and automobiles is rapidly increasing. The high specific calorific value, high octane number, clean and efficient combustion of LPG distinguish it as an extremely promising fuel of the future. In the current work, tungstophosphoric acid (TPA) supported on four different mesoporous silica supports were investigated as mesoporous superacids for hydroconversion of refinery naphtha using n-heptane as a model feedstock. The varied levels of interactions of prepared mesoporous silica with tungstophosphoric acid catalysts were observed to have a prominent effect on the strength of the acid sites generated on silica surfaces and as a result affected heptane hydroconversion activity and selectivity of isomerized and cracked products. Interestingly, activity could be tuned towards selective cracking or isomerization-cracking by selection of a suitable topology of mesoporous silica. Hexagonal Mesoporous Silica (HMS) and plugged SBA-15 supported TPA catalysts demonstrated high n-heptane conversion activity and isomerization selectivity whereas KIT-6 and SBA-15 supported TPA catalysts demonstrated high cracking selectivity to LPG.

TPA silanol interactions in mesoporous TPA silica composites govern the strength of acid sites, activity and selectivity.     

Wavelet Analysis of High-Resolution Signal-Averaged Electrocardiograms in Postinfarction Patients with Bundle Branch Block

Time-domain analysis of the signal-averaged electrocardiogram (SAECG) can accurately predict risk of sustained ventricular tachycardia (VT) in patients with previous myocardial infarction (MI). Unfortunately, these patients often have bundle branch block (BBB) that obscures late potentials. We hypothesized that wavelet analysis might help predict VT risk in patients with BBB. We identified subjects with coronary disease and BBB who had undergone SAECG and programmed ventricular stimulation (PVS). We applied a modulated Gaussian wavelet to transform the ECG signal and looked for singularities in the wavelet coefficients. SAECG and PVS were obtained in 32 patients. Half had inducible sustained monomorphic VT by PVS and half had no inducible VT. There were no significant clinical differences between the groups. Comparing the number of singularities, we found no significant difference between the groups. Compared to previous work in patients without BBB, our patients with BBB had on average four times more singula- rities using an identical analysis technique. In the presence of BBB, abnormal myocardial activation patterns can generate ECG waveforms with time–frequency characteristics similar to those of cardiac late potentials. Wavelet-based methodologies may have limited ability to distinguish late potentials from the disordered ventricular activation occurring with BBB alone.     

Continuous absence of metaphase-defined cytogenetic abnormalities,especially of chromosome 13 and hypodiploidy,ensures long-term survival in multiple myeloma treated with Total Therapy I: interpretation in the context of global gene expression

Metaphase cytogenetic abnormalities (CAs), especially of chromosome 13 (CA 13), confer a grave prognosis in multiple myeloma even with tandem autotransplantations as applied in Total Therapy I, which enrolled 231 patients between 1989 and 1994. With a median follow-up of almost 9 years, the prognostic implications of all individual CAs, detected prior to treatment and at relapse, were investigated. Among all CAs and standard prognostic factors examined prior to therapy, only hypodiploidy and CA 13 (hypo-13 CA), alone or in combination, were associated with shortest event-free survival and overall survival (OS). The shortest postrelapse OS was observed with hypo-13 CA, which was newly detected in 18 of all 28 patients presenting with this abnormality at relapse. Superior prognosis was associated with the absence of any CA at both diagnosis and relapse (10-year OS, 40%). The lack of independent prognostic implications of other CAs points to a uniquely aggressive behavior of hypo-13 CA (present in 16% of patients at diagnosis). With the use of microarray data in 146 patients enrolled in Total Therapy II, overexpression of cell cycle genes distinguished CA from no CA, especially in cases of del(13) detected by interphase fluorescence in situ hybridization (FISH). FISH 13, resulting in a haploinsufficiency of RB1 and other genes mapping to chromosome 13, as well as activation of IGF1R, appears to have an amplifying effect on cell cycle gene expression, thus providing a molecular explanation for the dire outcome of patients with CA 13 compared with those with other CAs.     

Immunotherapy for solid tumors—a review for surgeons

Immunotherapy has evolved considerably in the last decade and is becoming an integral component of the armamentarium for the treatment of patients with advanced solid tumors. It is important for clinicians, especially surgeons, to understand the basic principles of novel immunotherapies and the immune system. This review summarizes the evolution of the most relevant immunotherapies, their mechanisms of action, the data supporting their clinical use, and integration of immunotherapy into multidisciplinary management of solid tumors. This review should serve as a primer for clinicians and surgeons to understand the rapidly evolving field of immunotherapy.     

Round Pendant Around the Neck–Thyroid. A Review

The rare situation of thyroid stone is discussed with literature review and case report. A case of isolated solitary stone of the thyroid is documented here. There are incidences of calcification in the thyroid gland commonly associated with carcinoma thyroid and multinodular goiter. But solitary stone of thyroid is reported rarely and one such case is reported from India. The possibility of malignancy is high, in case of calcification of thyroid swellings. Hence, isolated calcification should be surgically treated even if fine needle aspiration cytology is negative for malignancy.     

Ameliorative effect of ferulic acid against renal injuries mediated by nuclear factor-kappaB during glycerol-induced nephrotoxicity in Wistar rats

The pathogenesis of glycerol-induced myoglobinuric acute renal failure involves ischemia, vascular congestion and reactive oxygen metabolites. In this study, we have investigated for the first time, the role of ferulic acid in attenuating glycerol-induced nephrotoxicity. Male Wistar rats were injected intramuscularly with 8?mL/kg body weight of 50% glycerol, glycerol?+?ferulic acid at the dose of 5, 10, 15, 20 and 25?mg/kg body weight. After 24?h, the rats were sacrificed and the kidneys were removed for histological and immunohistochemical studies. Furthermore, determinations of lipid peroxidation (LPO) as well as antioxidant enzymes were also analyzed; blood, urine samples were collected in order to quantify renal function and nitric oxide generation, respectively. Glycerol-induced rats showed a significant increase in the level of urinary markers assessed in serum as well as kidney and these were reversed upon ferulic acid treatment. A significant increase in urine nitric oxide, serum as well as kidney LPO, decrease in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and reduced glutathione were observed in glycerol-induced rats. Immunohistochemical study in glycerol-induced rats demonstrated an increase in the level of nuclear factor-kappaB (NF-κB). All these effects induced by glycerol were reduced upon treatment with ferulic acid in a dose-dependent manner. To conclude, ferulic acid enhances antioxidants and decreases NF-κB, thereby protecting the cells against stress induced by glycerol.