Opioid Use After Nephrectomy for Kidney Cancer in Ontario: A Population-Based Study.

OBJECTIVE: To compare the odds of early and prolonged post-operative opioid use in patients undergoing minimally invasive surgery (MIS) vs open surgery for nephrectomy. METHODS: For opioid-naïve patients in Ontario who underwent nephrectomy for kidney cancer (1994-2017, n = 7900), post-discharge opioid use was determined by prescriptions in the Ontario Drug Benefit database (age ≥65 years) and the Narcotics Monitoring System (all patients from 2012). Early opioid use was defined as ≥1 prescription 1-90 days after surgery. Two separate definitions of prolonged opioid use were examined: (1) prescription(s) for ≥60 days during post-operative days 90-365; (2) ≥1 prescriptions between both of: 1-90 days AND 91-180 days after surgery. Predictors of opioid use were assessed using multivariable generalized estimating equation logistic regression, accounting for surgeon clustering. RESULTS: Overall, 67.4% of patients received early opioid prescriptions; however, prolonged use was low, ranging from 1.6 to 4.4% of patients depending on the definition. In multivariable analysis, open nephrectomy was associated with higher odds of early opioid use compared to MIS nephrectomy (Odds Ratio [OR] 1.36, 95% Confidence Interval [CI] 1.19-1.55). Surgery type was not significantly associated with prolonged opioid use for either definition (OR 1.22, CI 0.79-1.89 and OR 1.06, CI 0.83-1.35). CONCLUSIONS: In this population-level study of patients undergoing nephrectomy for kidney cancer, patients who received open surgery were at increased odds of receiving early post-operative opioids compared to MIS. Prolonged opioid use was low overall and was not significantly with associated with type of surgery.

Real-World Practice Patterns and Predictors of Continuous versus Intermittent Androgen Deprivation Therapy Use for Prostate Cancer in Older Men.

PURPOSE: Phase-III randomized control trial evidence suggests intermittent androgen deprivation therapy (IADT) is not significantly inferior to continuous androgen deprivation therapy (ADT) for patients with prostate cancer (PC). However, clinical practice and guidelines differ in their recommendations. We evaluate real-world utilization and practice patterns of IADT. MATERIALS AND METHODS: Ontario men ≥65 years of age with PC who initiated ADT for ≥3 months were identified (1997-2017). Lapses in ADT ≥6 months (initial gap) and ≥3 months (subsequent gaps) were used to classify IADT. Neoadjuvant/adjuvant therapy was excluded. Disease stage adjustment was completed for patients with likely metastatic disease based on de novo presentation with ADT. Patient and physician predictors of IADT were analyzed using multivariable logistic regression. RESULTS: We identified 8,544 patients with 1,715 having previously received local therapy. Among all patients, 16.4% received IADT. This ranged from 11.4%-24.8% across health-planning regions and increased to 26.6% in those with previous local therapy. Mean followup was 8.3 years. Patients with prior local therapy (OR 1.85, 95% CI 1.59-2.17, p <0.001) and those in the highest income quintile (OR 1.32, 95% CI 1.08-1.60, p=0.005) had increased odds of receiving IADT. Radiation oncologists were more likely to use IADT than urologists (OR 1.99, 95% CI 1.59-2.50, p <0.001), as were physicians with more experience (≥10 years in practice: OR 1.44, 95% CI 1.11-1.88, p=0.007). In specialty-stratified analyses, case volume was significantly associated with IADT for radiation oncologists (highest quartile: OR 1.73, 95% CI 1.14-2.62, p=0.009). CONCLUSIONS: IADT remains underutilized for patients with PC who ≥65 years of age with only 1 in 4 to 1 in 6 eligible patients receiving this form of care. Clinical, sociodemographic and physician characteristics play an important role in treatment selection.

Adverse event profile for immunotherapy agents compared with chemotherapy in solid organ tumors: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Immunotherapy agents are an innovative oncological treatment modality and as a result their use has expanded widely. Understanding the treatment-related adverse events (AEs) of these drugs compared with traditional chemotherapy is crucial for clinical practice. DESIGN: A systematic review of studies indexed in Medline (PubMed), Embase, Web of Science, and the Cochrane Databases from January 2000 to 14 February 2019 was conducted. Randomized clinical trials comparing immunotherapy [cytotoxic T-lymphocyte protein-4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed death-ligand 1 (PD-L1)] with standard-of-care chemotherapy in the treatment of advanced solid-organ neoplasms were included if AEs were reported as an outcome. Primary outcome was AEs ≥ grade 3 in severity. Secondary outcomes were proportion of overall AEs, treatment discontinuation due to AEs, deaths due to AEs, and specific AEs [fatigue, diarrhea, acute kidney injury (AKI), colitis, pneumonitis, and hypothyroidism]. Paule-Mandel pooling and a random effects model were used to produce odds ratios (ORs) for measures of effects. RESULTS: Among 10 598 abstracts screened, we included 22 studies involving 12 727 patients. In the immunotherapy group, 16.5% of patients developed an AE ≥ grade 3 in severity, compared with 41.09% in the chemotherapy arm [OR = 0.26, 95% confidence interval (CI) 0.19-0.35, I2 = 92%]. Patients receiving immunotherapy also had lower odds of developing an AE overall (OR = 0.35, 95% CI 0.28-0.44; I2 = 77%), terminating therapy due to an AE (OR = 0.55, 95% CI 0.39-0.78, I2 = 80%), or dying from a treatment-related AE (OR = 0.67, 95% CI 0.46-0.98, I2 = 0%). When treated with chemotherapy versus immunotherapy, patients more frequently experienced fatigue (25.10% versus 15.83%), diarrhea (14.97% versus 11.13%), and AKI (1.79% versus 1.31%). However, colitis (1.02% versus 0.26%), pneumonitis (3.36% versus 0.36%), and hypothyroidism (6.82% versus 0.37%) were more common in those treated with immunotherapy. CONCLUSIONS: Treatment of advanced solid-organ malignancies with immunotherapy compared with traditional chemotherapy is associated with a lower risk of AEs.

Accuracy of valgus osteotomy using dynamic hip screw.

BACKGROUND: Non-union of neck femur is a common but difficult situation to manage especially in young adults. There are two main options of arthroplasty or osteotomy. The aim of this study was to assess the results of intertrochanteric valgus osteotomy in non-union femoral neck fractures. PATIENTS AND METHODS: We present a study of 44 cases of neck femur non-union including untreated fractures, late presentations (more than 3 weeks), treated with compression screw, DHS. From 2006-2016, 44 patients presented to our institute and we analyzed them prospectively on the following criteria: Pauwel's angle, Garden classification, union at fracture site, union at osteotomy site, osteoporosis and AVN changes. Inclusion criteria were age<65, neck not reabsorbed, no AVN. Powel's angle was calculated using the anatomic axis of femur. Wedge angle is equal to Powel's angle minus 30 degree. Entry point of DHS was at the base of greater trochanter and tip of the screw was in the inferior quadrant. Y osteotomy was done in the distal half of the lesser trochanter with a proximal straight cut. RESULTS: Complete union was noted in 93% of the cases. One patient with uncontrolled diabetes developed severe infection and was treated with excision arthoplasty. AVN occurred in 3 cases. The Powell's angle was reduced to mean 30 (22-39). The neck shaft angle was increased to mean 140 (130-150). Limp was noted in almost all patients but they were able to walk full weight bearing with or without the support of a stick. CONCLUSION: Valgus intertrochanteric osteotomy achieved good union rates and good functional outcome with minimal complications.

Correction of coronal plane deformities around the knee using a tension band plate in children younger than 10 years.

BACKGROUND: Guided growth through temporary hemiepiphysiodesis has gained acceptance as the preferred primary treatment in treating pediatric lower limb deformities as it is minimally invasive with a lesser morbidity than the traditional osteotomy. The tension band plate is the most recent development in implants used for temporary hemiepiphysiodesis. Our aim was to determine its safety and efficacy in correcting coronal plane deformities around the knee in children younger than 10 years. MATERIALS AND METHODS: A total of 24 children under the age of 10 were operated for coronal plane deformities around the knee with a single extra periosteal tension band plate and two nonlocking screws. All the children had a pathological deformity for which a detailed preoperative work-up was carried out to ascertain the cause of the deformity and rule out physiological ones. The average age at hemiepiphysiodesis was 5 years 3 months (range: 2 years to 9 years 1 month). RESULTS: The plates were inserted for an average of 15.625 months (range: 7 months to 29 months). All the patients showed improvement in the mechanical axis. Two patients showed partial correction. Two cases of screw loosening were observed. In the genu valgum group, the tibiofemoral angle improved from a preoperative mean of 19.89° valgus (range: 10° valgus to 40° valgus) to 5.72° valgus (range: 2° varus to 10° valgus). In patients with genu varum the tibiofemoral angle improved from a mean of 28.27° varus (range: 13° varus to 41° varus) to 1.59° valgus (range: 0-8° valgus). CONCLUSION: Temporary hemiepiphysiodesis through the application of the tension band plate is an effective method to correct coronal plane deformities around the knee with minimal complications. Its ease and accuracy of insertion has extended the indication of temporary hemiepiphysiodesis to patients younger than 10 years and across a wide variety of diagnosis including pathological physis, which were traditionally out of the purview of guided growth.

Complications following surgery with or without radiotherapy or radiotherapy alone for prostate cancer.

BACKGROUND: Men undergoing treatment of clinically localised prostate cancer may experience a number of treatment-related complications, which affect their quality of life. METHODS: On the basis of population-based retrospective cohort of men undergoing surgery, with or without subsequent radiotherapy, or radiotherapy alone for prostate cancer in Ontario, Canada, we measured the incidence of treatment-related complications using administrative and billing data. RESULTS: Of 36 984 patients, 15 870 (42.9%) underwent surgery alone, 4519 (12.2%) underwent surgery followed by radiotherapy, and 16 595 (44.9%) underwent radiotherapy alone. For all end points except urologic procedures, the 5-year cumulative incidence rates were lowest in the surgery only group and highest in the radiotherapy only group. Intermediary rates were seen in the surgery followed by radiotherapy group, except for urologic procedures where rates were the highest in this group. Although age and comorbidity were important predictors, radiotherapy as the primary treatment modality was associated with higher rates for all complications (adjusted hazard ratios 1.6-4.7, P=0.002 to <0.0001). CONCLUSIONS: In patients treated for prostate cancer, radiation after surgery increases the rate of complications compared with surgery alone, though these rates remain lower than patients treated with radiation alone. This information may inform patient and physician decision making in the treatment of prostate cancer.

Pre-treatment neutrophil-to-lymphocyte ratio as predictor of adverse outcomes in patients undergoing radical cystectomy for urothelial carcinoma of the bladder.

BACKGROUND: An elevated neutrophil-to-lymphocyte ratio (NLR) is associated with poor outcome in various tumours. Its prognostic utility in patients with urothelial carcinoma of the bladder (UCB) undergoing radical cystectomy (RC) is yet to be fully elucidated. METHODS: A cohort of patients undergoing RC for UCB in a tertiary referral centre between 1992 and 2012 was analysed. Neutrophil-to-lymphocyte ratio was computed using complete blood counts performed pre-RC, or before neo-adjuvant chemotherapy where applicable. Time-dependent receiver operating characteristic curves were used to determine the optimal cutoff point for predicting recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). The predictive ability of NLR was assessed using Kaplan-Meier analyses and multivariable Cox proportional hazards models. The likelihood-ratio test was used to determine whether multivariable models were improved by including NLR. RESULTS: The cohort included 424 patients followed for a median of 58.4 months. An NLR of 3 was determined as the optimal cutoff value. Patients with an NLR⩾3.0 had significantly worse survival outcomes (5y-RFS: 53% vs 64%, log-rank P=0.013; 5y-CSS: 57% vs 75%, log-rank P<0.001; 5y-OS: 43% vs 64%, log-rank P<0.001). After adjusting for disease-specific predictors, an NLR ⩾3.0 was significantly associated with worse RFS (HR=1.49; 95% CI=1.12-2.0, P=0.007), CSS (HR=1.88; 95% CI=1.39-2.54, P<0.001) and OS (average HR=1.67; 95% CI=1.17-2.39, P=0.005). The likelihood-ratio test confirmed that prognostic models were improved by including NLR. CONCLUSIONS: Neutrophil-to-lymphocyte ratio is an inexpensive prognostic biomarker for patients undergoing RC for UCB. It offers pre-treatment prognostic value in addition to established prognosticators and may be helpful in guiding treatment decisions.

Plating, nailing, external fixation, and fibular strut grafting for non-union of humeral shaft fractures.

PURPOSE: To compare various treatment modalities (plating, Ilizarov external fixation, and non-vascular fibular cortical strut grafting) for non-union of humeral shaft fractures. METHODS: Records of 9 women and 26 men aged 24 to 71 (mean, 42) years who presented with non-union of humeral shaft fractures were reviewed. The humeral shaft fractures were secondary to low-energy trauma (n=22) or vehicular accidents (n=13) and involved the proximal (n=9), middle (n=15), and distal (n=11) regions. 13 of the fractures were open. Infection was evident in 8 of the non-unions. For non-unions with infection (n=8), a 2-stage procedure entailing temporary Ilizarov fixation followed by plating was used. For non-unions without infection (n=23), one-stage plating and cancellous bone grafting was used. For non-unions of osteoporotic bone (n=4), one-stage non-vascularised fibular strut grafting was used. Outcome was measured using the Disabilities of the Arm, Shoulder and Hand (DASH) scoring system. RESULTS: The 35 patients were followed up for a mean of 16 (range, 6-60) months. All achieved bone union except for one (who had persistent infection). Respectively for non-unions with infection, nonunions without infection, and non-unions of osteoporotic bone, the mean times to bone union were 6.5 (range, 4-10), 5 (range, 4-8), and 10 (range, 6-14) months, the mean improvement in DASH score was 30, 43, and 18, and malalignment was noted in 5, 2, and one patient. Three patients had a preoperative radial nerve palsy for which standard tendon transfer was performed 6 weeks after treatment for non-union. CONCLUSION: Compression plating achieved the best results. An external fixator may be used temporarily for infected non-unions. Fibular strut grafting may be used when non-unions warrant additional stability.

Natural radioactivity study in soil samples of South Konkan, Maharashtra, India.

This study assesses the level of natural radioactivity due to radionuclides, ²³8U, ²³²Th and 4°K, in 50 soil samples collected from South Konkan, Maharashtra, India. The mean activity concentrations of ²³8U, ²³²Th and 4°K are 44.97 ± 1.22 Bq kg⁻¹, 59.70 ± 2.17 Bq kg⁻¹ and 217.51 ± 8.75 Bq kg⁻¹, respectively, measured from all the soil samples studied. The good correlation between activity concentration of U-238 and Th-232; U-238 and K-40 as well as between activity concentration of Th-232 and K-40 was observed. The average calculated absorbed dose rate in air (68.08 nGy h⁻¹) was found to be higher than the world average of 57 nGy h⁻¹ (UNSCEAR 2000). Radium equivalent activity for all the villages was found to be lower than the worldwide value. The values of external hazard index and internal hazard index determined from all the soil samples were found to be within recommended limit. The calculated average annual effective dose was found to be 0.42 mSv y⁻¹, and it is lower than the worldwide value of 0.46 mSv y⁻¹.The annual effective dose values calculated from present study were comparable with previous studies carried out in other countries and in India. The data established from the study can be useful as baseline information on natural radioactivity in South Konkan, Maharashtra, India.

Management of severe extra-articular contracture of the elbow by open arthrolysis and a monolateral hinged external fixator.

Arthrolysis and dynamic splinting have been used in the treatment of elbow contractures, but there is no standardised protocol for treatment of severe contractures with an arc of flexion < 30 degrees . We present our results of radical arthrolysis with twin incisions with the use of a monolateral hinged fixator to treat very severe extra-articular contracture of the elbow. This retrospective study included 26 patients (15 males and 11 females) with a mean age of 30 years (12 to 60). The mean duration of stiffness was 9.1 months (5.4 to 18) with mean follow-up of 5.2 years (3.5 to 9.4). The mean pre-operative arc of movement was 15.6 degrees (0 degrees to 30 degrees ), with mean pre-operative flexion of 64.1 degrees (30 degrees to 120 degrees ) and mean pre-operative extension of 52.1 degrees (10 degrees to 90 degrees ). Post-operatively the mean arc improved to 102.4 degrees (60 degrees to 135 degrees ), the mean flexion improved to 119.1 degrees (90 degrees to 140 degrees ) and mean extension improved to 16.8 degrees (0 degrees to 30 degrees ) (p < 0.001). The Mayo elbow score improved from a mean of 45 (30 to 65) to 89 (75 to 100) points, and 13 had excellent, nine had good, three had fair and one had a poor result. We had one case of severe instability and one wound dehiscence which responded well to treatment. One case had deep infection with poor results which responded well to treatment. Our findings indicate that this method is very effective in the treatment of severe elbow contracture; however, a randomised controlled study is necessary for further evaluation.