Effectiveness of Physical Therapy Combined With Epidural Steroid Injection for Individuals With Lumbar Spinal Stenosis: A Randomized Parallel-Group Trial

Objective

To examine the effectiveness of epidural steroid injection (ESI) and back education with and without physical therapy (PT) in individuals with lumbar spinal stenosis (LSS).

Percutaneous radiofrequency ablation of hepatocellular carcinoma as a bridge to liver transplantation

Orthotopic liver transplantation (OLT) can be a definitive treatment for patients with hepatocellular carcinoma (HCC). Prolonged waiting times for cadaveric livers, however, may lead to dropout from the waiting list or worsened post-OLT prognosis as a result of interval tumor progression. Percutaneous radiofrequency ablation (RFA) is widely used for local control of small unresectable HCC, but its pretransplant role remains unclear. We studied the outcome of 52 consecutive patients accepted for OLT bearing 87 HCC nodules and treated with percutaneous RFA. On initial staging, the tumor burden exceeded the Milan criteria in 10 patients. Complete tumor coagulation was observed in 74 of 87 (85.1%) nodules based on postablation imaging. After a mean of 12.7 months (range: 0.3-43.5) on the waiting list, 3 of 52 patients (5.8%) had dropped out due to tumor progression. Forty-one patients had undergone transplantation, with 1- and 3-year post-OLT survival rates of 85% and 76%, respectively. No patient developed HCC recurrence. There were three major complications in 76 RFA procedures (hepatic arterial hemorrhage, small bowel perforation, and liver decompensation salvaged by OLT), without resultant death or dropout. In conclusion, percutaneous RFA is an effective bridge to OLT for patients with compensated liver function and safely accessible tumors. Tumor-related dropout rate and post-OLT outcome compared favorably with published controls of patients with early-stage disease. This can be attributed to the efficacy of RFA in producing local cure or curbing tumor progression during the waiting period.     

Podophyllum hexandrum Offers Radioprotection by Modulating Free Radical Flux: Role of Aryl-Tetralin Lignans

We have evaluated the effect of variation in aryl-tetralin lignans on the radioprotective properties of Podophyllum hexandrum. Two fractionated fractions of P. hexandrum [methanolic (S1) and chloroform fractions (S2)], with varying aryl-tetralin lignan content were utilized for the present study. The peroxyl ion scavenging potentials of S1 and S2 were found to be comparable [i.e. 45.88% (S1) and 41% (S2)] after a 48 h interval in a time-dependent study, whereas in a 2 h study, S2 exhibited significant (P < 0.05) antioxidant activity in different metal ion + flux states. In the aqueous phase, S2 exhibited non-site-specific reactive oxygen species scavenging activity, i.e. 73.12% inhibition at 500 mug ml(-1). S1 exhibited 58.40 +/- 0.8% inhibition (at 0.025 mug ml(-1)) of the formation of reactive nitrite radicals, comparable to S2 (52.45 +/- 0.825%), and also showed 45.01% site-specific activity (1000 mug ml(-1)), along with significant (P < 0.05) electron donation potential (50-2000 mug ml(-1)) compared to S2. Such activities of S1 could be attributed to the significantly (P < 0.05) higher levels of podophyllotoxin beta-d-glucopyranoside (16.5 times) and demethyl podophyllotoxin glucoside (2.9 times) compared with S2. Together, these findings clearly prove that aryl-tetralin lignan content influences the radiation protective potential of the Podophyllum fractions to a great extent.     

At-risk but viable myocardium in a large animal model of non ST-segment elevation acute coronary syndrome: cardiovascular magnetic resonance with ex vivo validation

Background

Patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) have varying degrees of salvageable myocardium at risk of irreversible injury. We hypothesized that a novel model of NSTE-ACS produces acute myocardial injury, measured by increased T2 cardiovascular magnetic resonance (CMR), without significant necrosis by late gadolinium enhancement (LGE).

Methods

In a canine model, partial coronary stenosis was created and electrodes placed on the epicardium. Myocardial T2, an indicator of at-risk myocardium, was measured pre- and post-tachycardic pacing.

Results

Serum troponin-I (TnI) was not detectable in unoperated sham animals but averaged 1.97 ± 0.72 ng/mL in model animals. Coronary stenosis and pacing produced significantly higher T2 in the affected vs. the remote myocardium (53.2 ± 4.9 vs. 43.6 ± 2.8 ms, p < 0.01) with no evident injury by LGE. Microscopy revealed no significant irreversible cellular injury. Relative respiration rate (RRR) of affected vs. remote myocardial tissue was significantly lower in model vs. sham animals (0.72 ± 0.07 vs. 1.04 ± 0.07, p < 0.001). Lower RRR corresponded to higher final TnI levels (R² = 0.83, p = 0.004) and changes in CaMKIID and mitochondrial gene expression.

Conclusions

A large animal NSTE-ACS model with mild TnI elevation and without ST elevation, similar to the human syndrome, demonstrates signs of acute myocardial injury by T2-CMR without significant irreversible damage. Reduced tissue respiration and associated adaptations of critical metabolic pathways correspond to increased myocardial injury by serum biomarkers in this model. T2-CMR as a biomarker of at-risk but salvageable myocardium warrants further consideration in preclinical and clinical studies of NSTE-ACS.     

Promising role of preoperative neutrophil-to-lymphocyte ratio in patients treated with radical nephroureterectomy

Objective

Several retrospective studies with small cohorts reported neutrophil-to-lymphocyte ratio (NLR) as a prognostic marker in upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU). We aimed at validating the predictive and prognostic role of NLR in a large multi-institutional cohort.

Methods

Preoperative NLR was assessed in a multi-institutional cohort of 2477 patients with UTUC treated with RNU. Altered NLR was defined by a ratio >2.7. Logistic regression analyses were performed to assess the association between NLR and lymph node metastasis, muscle-invasive and non-organ-confined disease. The association of altered NLR with recurrence-free survival (RFS) and cancer-specific survival (CSS) was evaluated using Cox proportional hazards regression models.

Results

Altered NLR was observed in 1428 (62.8 %) patients and associated with more advanced pathological tumor stage, lymph node metastasis, lymphovascular invasion, tumor necrosis and sessile tumor architecture. In a preoperative model that included age, gender, tumor location and architecture, NLR was an independent predictive factor for the presence of lymph node metastasis, muscle-invasive and non-organ-confined disease (p < 0.001). Within a median follow-up of 40 months (IQR 20–76 months), 548 (24.1 %) patients experienced disease recurrence and 453 patients (19.9 %) died from their cancer. Compared to patients with normal NLR, those with altered NLR had worse RFS (0.003) and CSS (p = 0.002). In multivariable analyses that adjusted for the effects of standard clinicopathologic features, altered NLR did not retain an independent value. In the subgroup of patients treated with lymphadenectomy in addition to RNU, NLR was independently associated with CSS (p = 0.03).

Conclusion

In UTUC, preoperative NLR is associated with adverse clinicopathologic features and independently predicts features of biologically and clinically aggressive UTUC such as lymph node metastasis, muscle-invasive or non-organ-confined status. NLR may help better risk stratify patients with regard to lymphadenectomy and conservative therapy.

     

Intratumoral Heterogeneity of Bladder Cancer by Molecular Subtypes and Histologic Variants

Molecular subtyping may inform on prognosis and treatment response in bladder cancer. However, intratumoral molecular heterogeneity is not well studied in this disease and could complicate efforts to use molecular subtyping to guide patient management. To investigate intratumoral heterogeneity in bladder cancer, we examined molecular subtypes in a consecutive, retrospective cystectomy series of histologic variant bladder cancers and conventional urothelial carcinomas co-occurring with them. Molecular subtypes were assigned as per the approach reported by Lund University, an approach that incorporates cell cycle alterations and markers of differentiation, to give the urothelial-like, genomically unstable, basal-squamous, mesenchymal-like, and neuroendocrine-like subtypes. The majority (93%) of tumors were classified as urothelial like, genomically unstable, or basal squamous. Among patients with more than one tumor histology, 39% demonstrated molecular heterogeneity among the different tumor histologies. This was greatest for the basal-squamous subtype, 78% of which co-occurred with either urothelial-like or genomically unstable carcinoma (among cases with multiple histologies). In contrast, there was no co-occurrence of urothelial-like and genomically unstable carcinoma in the same patient. The findings indicate that bladder cancer is often molecularly heterogeneous, particularly in the basal-squamous subtype. This raises the concern for sampling error in laboratory tests that guide therapy based on molecular subtyping.Patient summary: In this report, we investigated molecular diversity among different areas from the same tumor in patients with bladder cancer. We found that different areas from the same tumor are often molecularly different. We conclude that this biological diversity must be taken into account when interpreting clinical molecular tests performed on bladder cancer samples.     

Primary cardiac lymphoma masquerading as right atrial myxoma causing complete heart block—a case report

Secondary involvement of the heart and pericardium by systemic lymphoma is well documented. Primary Cardiac lymphomas (PCL) are extremely rare. Incidence of PCL is increasing in immunocompromised patients. However PCL in immunocompetent is much rarer. We report such a case of PCL in an immunocompetent elderly female masquerading as right atrial myxoma causing complete heart block which was surgically debulked successfully. Her rhythm resumed to Sinus rhythm following surgical debulking. Immunohistochemistry of the excised tumour revealed Diffuse Large B cell lymphoma. With combination chemotherapy, she is symptom free on six months follow up.