Characterizing trends in treatment modalities for localized muscle-invasive bladder cancer in the pre-immunotherapy era

Introduction

Muscle-invasive bladder cancer (MIBC) is an aggressive disease for which treatment strategies are continuously evolving. We characterized trends in treatment modalities for MIBC from 2004 to 2013 (the “pre-immunotherapy era”) and identified predictors of receiving the current standard of care treatment: neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC).

Methods

We used the National Cancer Database to identify individuals diagnosed with clinically localized MIBC from 2004 to 2013. We calculated the yearly prevalence of NAC followed by RC, RC as first treatment, trimodal therapy, chemotherapy and/or radiation alone, and no treatment. We then identified factors associated with receiving NAC prior to RC.

Results

There was a notable increase in the use of NAC followed by RC over the study period, from 3.68% in 2004 to 14.83% in 2013 (P?<?0.001). Factors associated with decreased odds of receiving this regimen included being older, Black, uninsured, less educated, and more burdened by comorbidities. Rates of trimodal therapy and chemotherapy and/or radiation alone remained relatively constant (approximately 5 and 17%, respectively). There was a consistent decline in the proportion of patients who did not receive any treatment, down to 34.20% in 2013.

Conclusion

Trends in localized MIBC treatment have evolved substantially since the early 2000s, and certain patient characteristics are associated with lower odds of receiving the current standard of care. This serves as a foundation from which to judge the impact of the upcoming immunotherapy era on the treatment landscape for this disease.

     

Fresh Osteochondral Allograft Transplantation for Treatment of Large Cartilage Defects of the Femoral Head: A Minimum Two-Year Follow-Up Study of Twenty-Two Patients

Background

Controversy remains over the surgical management of large osteochondral lesions of the femoral head in young, active patients. The purpose of this study is to assess midterm clinical and radiographic outcomes after fresh osteochondral allograft transplantation (OAT) for large femoral head lesions at minimum 2-year follow-up.

Botulinum Toxin-induced Muscle Paralysis Inhibits Heterotopic Bone Formation

Background

Short-term muscle atrophy induced by botulinum toxin A (BTxA) has been observed to impair osteogenesis in a rat closed femur fracture model. However, it is unclear whether the underlying mechanism is a direct effect of BTxA on muscle-bone interactions or an indirect effect that is driven by skeletal unloading. Because skeletal trauma in the closed fracture model also leads to disuse atrophy, we sought to mitigate this confounding variable by examining BTxA effects on muscle-bone interactions in two complementary in vivo models in which osteogenesis is induced in the absence of skeletal unloading. The overall aim of this study was to identify a potential strategy to inhibit pathological bone formation and heterotopic ossification (HO).

Questions/purposes

(1) Does muscle paralysis inhibit periosteal osteogenesis induced by a transcortical defect? (2) Does muscle paralysis inhibit heterotopic bone formation stimulated by intramuscular bone morphogenetic protein (BMP) injection?

Methods

Focal osteogenesis was induced in the right hindlimb of mice through surgical initiation of a small transcortical defect in the tibia (fracture callus; n = 7/group) or intramuscular injection of BMP-2 (HO lesion; n = 6/group), both in the presence/absence of adjacent calf paralysis. High-resolution micro-CT images were obtained in all experimental groups 21 days postinduction and total volume (ie, perimeter of periosteal callus or HO lesion) and bone volume (calcified tissue within the total volume) were quantified as primary outcome measures. Finally, these outcome measures were compared to determine the effect of muscle paralysis on inhibition of local osteogenesis in both studies.

Results

After a transcortical defect, BTxA-treated mice showed profound inhibition of osteogenesis in the periosteal fracture callus 21 days postsurgery compared with saline-treated mice (total volume: 0.08 ± 0.06 versus 0.42 ± 0.11 mm³, p < 0.001; bone volume: 0.07 ± 0.05 versus 0.32 ± 0.07 mm³, p < 0.001). Similarly, BMP-2-induced HO formation was inhibited by adjacent muscle paralysis at the same time point (total volume: 1.42 ± 0.31 versus 3.42 ± 2.11 mm³, p = 0.034; bone volume: 0.68 ± 0.18 versus 1.36 ± 0.79 mm³, p = 0.045).

Conclusions

Our data indicate that BTxA-induced neuromuscular inhibition mitigated osteogenesis associated with both a transcortical defect and BMP-2-induced HO.

Clinical Relevance

Focal neuromuscular inhibition represents a promising new approach that may lead to a new clinical intervention to mitigate trauma-induced HO, a healthcare challenge that is severely debilitating for civilian and war-wounded populations, is costly to both the patient and the healthcare system, and currently lacks effective treatments.     

Comparison of catheter tip migration using flexible and stimulating catheters inserted into the adductor canal in a cadaver model

Use of adductor canal blocks and catheters for perioperative pain management following total knee arthroplasty is becoming increasingly common. However, the optimal equipment, timing of catheter insertion, and catheter dislodgement rate remain unknown. A previous study has suggested, but not proven, that non-tunneled stimulating catheters may be at increased risk for catheter migration and dislodgement after knee manipulation. We designed this follow-up study to directly compare tip migration of two catheter types after knee range of motion exercises. In a male unembalmed human cadaver, 30 catheter insertion trials were randomly assigned to one of two catheter types: flexible or stimulating. All catheters were inserted using an ultrasound-guided short-axis in-plane technique. Intraoperative knee manipulation similar to that performed during surgery was simulated by five sequential range of motion exercises. A blinded regional anesthesiologist performed caliper measurements on the ultrasound images before and after exercise. Changes in catheter tip to nerve distance (p = 0.547) and catheter length within the adductor canal (p = 0.498) were not different between groups. Therefore, catheter type may not affect the risk of catheter tip migration when placed prior to knee arthroplasty.