Operative and Functional Outcome After Pulmonary Endarterectomy for Advanced Thromboembolic Pulmonary Hypertension

Aim

To evaluate the midterm hemodynamic and functional outcome of pulmonary endarterectomy (PEA) for patients with advanced chronic thromboembolic pulmonary hypertension (CTEPH).

Methods

Thirty‐eight consecutive patients underwent PEA for CTEPH from May 2004 to March 2012. All patients were followed prospectively at six months postoperatively and annually thereafter. Each patient underwent serial cardiopulmonary exercise testing (CPET) and transthoracic echocardiography, and were followed for up to four years.

Results

Overall, 31.5% (12/38) of patients had Jamieson class II disease while 65.8% (25/38) had class III disease. There were three in‐hospital mortalities (7.9%), all of which had baseline pulmonary vasculature resistance (PVR) greater than 1400 dynes‐sec‐cm^?5. Preoperative PVR and mean pulmonary artery pressure were 1209 ± 723 dynes‐sec‐cm^?5 and 50 ± 14 mmHg, respectively, signifying a high‐risk operative group. Ninety‐seven percent of patients were in NYHA class III or IV preoperatively. At median follow‐up of 29 months 89.5% (17/19) of patients were in NYHA class I or II. CPET revealed a progressive increase in peak oxygen consumption from 16.5 ± 4.1 ml/kg/min at first follow‐up, to a plateau of 20.2 ± 5.6 ml/kg/min (p = 0.032) at two years.

Conclusions

CPET can be used to quantify progress in functional capacity post‐CTEPH, although improvements in peak oxygen consumption plateau at two years. doi: 10.1111/jocs.12646 (J Card Surg 2016;31:3–8)

     

Early sacral neuromodulation ameliorates urinary bladder function and structure in complete spinal cord injury minipigs

Aims

To determine the effects of early sacral neuromodulation (SNM) and pudendal neuromodulation (PNM) on lower urinary tract (LUT) function, minipigs with complete spinal cord injury (cSCI) were analyzed. SNM and PNM have been proposed as therapeutic approaches to improve bladder function, for example after cSCI. However, further evidence on efficacy is required before these methods can become clinical practice.

Methods

Eleven adults, female Göttingen minipigs with cSCI at vertebral level T11-T12 were included: SNM (n = 4), PNM (n = 4), and SCI control (SCIC: n = 3). Tissue from six healthy minipigs was used for structural comparisons. Stimulation was started 1 week after cSCI. Awake urodynamics was performed on a weekly basis. After 16 weeks follow-up, samples from the urinary bladder were taken for analyses.

Results

SNM improved bladder function with better capacities and lower detrusor pressures at voiding and avoided the emergence of detrusor sphincter dyssynergia (DSD). PNM and untreated SCI minipigs had less favorable outcomes with either DSD or constant urinary retention. Structural results revealed SCI-typical fibrotic alterations in all cSCI minipigs. However, SNM showed a better-balanced distribution of smooth muscle to connective tissue with a trend towards the reduced progression of bladder wall scarring.

Conclusion

Early SNM led to an avoidance of the emergence of DSD showing a more physiological bladder function during a 4 month follow-up period after cSCI. This study might pave the way for the clinical continuation of early SNM for the treatment of neurogenic LUT dysfunction after SCI.

     

Acute effect of sacral neuromodulation for treatment of detrusor overactivity on urodynamic parameters

Aim

The aim of this study is to evaluate the acute effects of sacral neuromodulation (SNM) on various urodynamic parameters.

Methods

Patients with overactive bladder and detrusor overactivity (DO) who were planned for percutaneous nerve evaluation (PNE) were included. Directly after the PNE, a urodynamic study (UDS) was performed. The stimulation was turned off during the first UDS (UDS 1), and during the second filling cycle, stimulation was turned on (UDS 2). The UDS was followed by a test phase of 1 week and the bladder diaries were evaluated during an outpatient clinic visit. Primary outcome measures were the differences in UDS parameter values with SNM off and on.

Results

Ten female patients were included in the study and completed the study protocol. Eight patients showed ≥50% improvement of symptoms following a test phase. There were no differences between UDS 1 and UDS 2 in the UDS parameters; bladder volume at first sensation, bladder volume at first DO, highest DO pressure, bladder capacity, maximum flow rate, and pressure at maximum flow rate.

Discussion

None of the aforementioned urodynamic parameters was influenced by acute SNM in patients who responded to SNM. To the best of our knowledge, this is the first study investigating the acute effects of SNM on bladder function.

     

PTEN and ERG expression in MRI-ultrasound guided fusion biopsy correlated with radical prostatectomy findings in men with prostate cancer

Background

Conventional systematic prostate biopsies (SBx) have multiple limitations, and magnetic resonance imaging (MRI)-ultrasound fusion targeting is increasingly applied (fusion biopsies [FBx]). In our previous studies, we have shown that loss of the tumor suppressor gene phosphatase and tensin homolog (PTEN) in radical prostatectomy (RP) specimens predicts poor disease-specific survival, and in active surveillance (AS), PTEN loss in SBx predicts an adverse AS outcome, although SBx PTEN status does not correlate well with the corresponding RP status. Here, we have hypothesized that PTEN and erythroblast transformation-specific related gene (ERG) status in FBx correlate better with RP than they would in SBx.

Methods

A total of 106 men, who had undergone FBx and subsequent RP in a single center between June 2015 and May 2017 were included. Fifty-three of the men had concomitant or previous SBx's. All biopsy and RP specimens were collected, and tissue microarrays (TMA) were constructed from RP specimens. Immunohistochemical stainings for PTEN and ERG expression were conducted on biopsies and RP TMAs and results were compared by using Fisher's exact test.

Results

The immunohistochemical predictive power of FBx, determined by the concordance of biopsy PTEN and ERG status with RP, is superior to SBx (77.6% vs 66.7% in PTEN, 92.4% vs 66.6% in ERG). FBx was superior to SBx in correlation with RP Gleason Grade Groups and MRI prostate imaging reporting and data system scores.

Conclusion

FBx grading correlates with RP histology and MRI findings and predicts the biomarker status in the RP specimens more accurately than SBx. A longer follow-up is needed to evaluate if this translates to better prediction of disease outcomes, especially in AS and radiation therapy where prostatectomy specimens are not available for prognostication.

     

Lung volume changes in Apnoeic Oxygenation using Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) compared to mechanical ventilation in adults undergoing laryngeal surgery

Background

Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) using high-flow 100% oxygen during apnoea has gained increased use during difficult airway management and laryngeal surgery due to a slower carbon dioxide rise compared to traditional apnoeic oxygenation. We have previously demonstrated high arterial oxygen partial pressures and an increasing arterial-alveolar carbon dioxide difference during THRIVE. Primary aim of this study was to characterise lung volume changes measured with electrical impedance tomography during THRIVE compared to mechanical ventilation.

Methods

Thirty adult patients undergoing laryngeal surgery under general anaesthesia were randomised to THRIVE or mechanical ventilation. Subjects were monitored with electrical impedance tomography and repeated blood gas measurement perioperatively. The THRIVE group received 100% oxygen at 70 l min⁻¹ during apnoea. The mechanical ventilation group was intubated and normoventilated with an FiO₂ of 0.4.

Results

Mean age were 48.2 (19.9) and 51.3 (12.3) years, and BMI 26.0 (4.5) and 26.0 (3.9) in the THRIVE and mechanical ventilation group respectively. Mean apnoea time in the THRIVE group was 17.9 (4.8) min. Mean apnoea to end-of-surgery time was 28.1 (12.8) min in the mechanical ventilation group. No difference in delta End Expiratory Lung Impedance was seen between groups over time. In the THRIVE group all but three subjects were well oxygenated during apnoea. THRIVE was discontinued for the three patients who desaturated.

Conclusions

No difference in lung volume change over time, measured by electrical impedance tomography, was detected when using THRIVE compared to mechanical ventilation during laryngeal surgery.

     

Development of a multivariable risk model integrating urinary cell DNA methylation and cell-free RNA data for the detection of significant prostate cancer

Background

Prostate cancer exhibits severe clinical heterogeneity and there is a critical need for clinically implementable tools able to precisely and noninvasively identify patients that can either be safely removed from treatment pathways or those requiring further follow up. Our objectives were to develop a multivariable risk prediction model through the integration of clinical, urine-derived cell-free messenger RNA (cf-RNA) and urine cell DNA methylation data capable of noninvasively detecting significant prostate cancer in biopsy naïve patients.

Methods

Post-digital rectal examination urine samples previously analyzed separately for both cellular methylation and cf-RNA expression within the Movember GAP1 urine biomarker cohort were selected for a fully integrated analysis (n = 207). A robust feature selection framework, based on bootstrap resampling and permutation, was utilized to find the optimal combination of clinical and urinary markers in a random forest model, deemed ExoMeth. Out-of-bag predictions from ExoMeth were used for diagnostic evaluation in men with a clinical suspicion of prostate cancer (PSA ≥ 4 ng/mL, adverse digital rectal examination, age, or lower urinary tract symptoms).

Results

As ExoMeth risk score (range, 0-1) increased, the likelihood of high-grade disease being detected on biopsy was significantly greater (odds ratio = 2.04 per 0.1 ExoMeth increase, 95% confidence interval [CI]: 1.78-2.35). On an initial TRUS biopsy, ExoMeth accurately predicted the presence of Gleason score ≥3 + 4, area under the receiver-operator characteristic curve (AUC) = 0.89 (95% CI: 0.84-0.93) and was additionally capable of detecting any cancer on biopsy, AUC = 0.91 (95% CI: 0.87-0.95). Application of ExoMeth provided a net benefit over current standards of care and has the potential to reduce unnecessary biopsies by 66% when a risk threshold of 0.25 is accepted.

Conclusion

Integration of urinary biomarkers across multiple assay methods has greater diagnostic ability than either method in isolation, providing superior predictive ability of biopsy outcomes. ExoMeth represents a more holistic view of urinary biomarkers and has the potential to result in substantial changes to how patients suspected of harboring prostate cancer are diagnosed.

     

Mortality and renal prognosis in isolated metformin-associated lactic acidosis treated with continuous renal replacement therapy and citrate-calcium-anticoagulation

Introduction

Use of metformin increases plasma lactate concentration and may lead to metformin-associated lactic acidosis (MALA). Previous studies have suggested severe MALA to have a mortality of 17%-21%, but have included patients with other coincident conditions such as sepsis. The treatment of choice is continuous renal replacement therapy (CRRT), which has been performed using heparin analogues or no anticoagulation in former studies.

Materials and Methods

Patients admitted to the Intensive Care Unit of Turku University Hospital Finland with lactic acidosis without any other recognizable etiology than concomitant metformin treatment who required CRRT between years 2010 and 2019 were included. CRRT was performed using regional citrate-calcium-anticoagulation. Data extracted included patient demographics, comorbidities, and clinical parameters at 6-hour intervals about 72 hours from admission. Creatinine and estimated glomerular filtration rate (eGFR) were measured at 1 year after MALA.

Results

A total of 23 patients with isolated MALA were included in the study. Median (IQR) pH was 6.88 (6.81-7.07) and lactate 16.1 (11.9-23.0) mmol/L on admission. Median (IQR) duration of CRRT was 62 (41-70) hours. Seven patients (30%) required mechanical ventilation with a mean duration of 6.0 ± 3.0 days. 90-day mortality was 4.3% and 1-year mortality 13.0%. Creatinine (P = .02) and eGFR (P = .03) remained significantly altered at 1 year of follow-up compared to baseline.

Conclusions

MALA can be treated effectively and safely with CRRT and citrate-calcium-anticoagulation, usually required for 2-3 days. Mortality of patients with MALA treated with CRRT is low when other conditions inducing lactic acidosis are excluded. MALA episode may be associated with long-lasting kidney injury.

     

Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial—Protocol and statistical analysis plan

Introduction

Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.

Methods

The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.

Discussion

The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.

     

Association among plasma 1,25(OH)2D,ratio of 1,25(OH)2D to 25(OH)D,and prostate cancer aggressiveness

Background

African-American (AA) men tend to present with more aggressive prostate cancer (Gleason score >7) than European-American (EA) men. Vitamin D and its metabolites are implicated in prostate cancer biology with vitamin D deficiency, indicated by its metabolite levels in serum or plasma, usually observed in AA men.

Objective

To determine if 1, 25-dihydroxy vitamin D3 [1,25(OH)₂D] plasma levels in AA and EA prostate cancer patients alter the risk of having aggressive prostate cancer.

Design

Research subjects from the North Carolina-Louisiana Prostate Cancer Project (AA n = 435 and EA n = 532) were included. Plasma metabolites 1,25(OH)₂D and 25-hydroxyvitamin D3 [25(OH)D] were measured using liquid chromatography with tandem mass spectrophotometry. Research subjects were classified into low (Gleason sum < 7, stage T1-T2, and Prostate-specific antigen (PSA) < 9 ng/mL) or high (Gleason sum > 8 or Gleason sum = 7 with 4 + 3, or PSA > 20 ng/mL, or Gleason sum = 7 and stage T3-T4) aggressive disease.

Results

Research subjects in the second and third tertiles of plasma levels of 1, 25(OH)₂D had lower odds of high aggressive prostate cancer (AA [OR_T2vsT1: 0.66, 95%CI: 0.39-1.12; OR_T3vsT1: 0.83, 95%CI: 0.49-1.41] and EA [OR_T2vsT1: 0.68, 95%CI: 0.41-1.11; OR_T3vsT1: 0.67, 95%CI: 0.40-1.11]) compared with the first tertile, though confidence intervals included the null. Greater 1,25(OH)₂D/25(OH)D molar ratios were associated with lower odds of high aggressive prostate cancer more evidently in AA (OR_Q4vsQ1: 0.45, CI: 0.24-0.82) than in EA (OR_Q4vsQ1: 0.64, CI: 0.35-1.17) research subjects.

Conclusions

The 1,25(OH)₂D/25(OH)D molar ratio was associated with decreased risk of high aggressive prostate cancer in AA men, and possibly in EA men. Further studies analyzing vitamin D polymorphisms, vitamin D binding protein levels, and prostatic levels of these metabolites may be useful. These studies may provide a better understanding of the vitamin D pathway and its biological role underlying health disparities in prostate cancer.

     

Safety and Efficacy of a Non-Invasive High-Intensity Focused Electromagnetic Field (HIFEM) Device for Treatment of Urinary Incontinence and Enhancement of Quality of Life

Background and Objectives

Urinary incontinence is a common and distressing condition which interferes with everyday life. Patients frequently experience discomfort related to urine leakage and the subsequent need to use absorbent pads. Since the continence mechanism is primarily maintained by a proper function of pelvic floor muscles (PFM), many treatment methods focused on strengthening of the PFM have been introduced in the past. The aim of this study was to evaluate the safety and efficacy of a high-intensity focused electromagnetic technology (HIFEM) for treatment of urinary incontinence with emphasis on effects on prospective patients’ quality of life.

Study Design/Materials and Methods

The study followed an institutional review board approved protocol. A total of 75 women (55.45 ± 12.80 years, 1.85 ± 1.28 deliveries) who showed symptoms of stress, urge, or mixed urinary incontinence were enrolled. They received six HIFEM treatments (2 per week) in duration of 28 minutes. Outcomes were evaluated after the sixth treatment and at the 3-month follow-up. The primary outcome was to assess changes in urinary incontinence by the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and changes in the number of absorbent pads used per day. The secondary outcome was subjective evaluation of the therapy and self-reported changes in quality of life. The statistical analysis was conducted by paired T-test and Pearson correlation coefficient ( α = 0.05).

Results

After the sixth session, 61 out of 75 patients (81.33%) reported significant reduction of their symptoms. The average improvement of 49.93% in ICIQ-SF score was observed after the sixth treatment, which further increased to 64.42% at the follow-up (both P < 0.001). Individually, the highest level of improvement was reached in patients suffering from mixed urinary incontinence (69.90%). The reduction of absorbent pads averaged 43.80% after the sixth treatment and 53.68% at 3 months (both P < 0.001), while almost 70% of patients (30 out of 43) reported decreased number of used pads. At the follow-up, a highly significant medium correlation (r = 0.53, P < 0.001) was found between the ICIQ-SF score improvement and the reduction in pad usage. A substantial decrease in the frequency of urine leakage triggers was documented. Patients reported no pain, downtime or adverse events, and also reported additional beneficial effects of the therapy such as increased sexual desire and better urination control.

Conclusions

This study demonstrated that HIFEM technology is able to safely and effectively treat a wide range of patients suffering from urinary incontinence. After six treatments, an improvement in ICIQ-SF score and reduction in absorbent pads usage was observed. Based on subjective evaluation, these changes positively influenced quality of life. © 2019 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

     

Accuracy of administrative coding data in colorectal cancer resections and short‐term outcomes

Background

Administrative data are routinely captured for each hospital admission and may serve as an alternative source for populating databases. This study aims to determine the accuracy of administrative data to provide tumour characteristics and short‐term post‐operative outcomes, after a colorectal cancer (CRC) resection, compared with clinical data.

Methods

A retrospective study of all CRC resections at a single hospital from 1 January 2008 to 31 December 2013 was conducted. Local administrative data were coded as per ICD‐10‐AM (International Classification of Diseases, Tenth Revision, Australian Modification) and Australian Classification of Health Interventions. Clinical data for all patients were extracted from the medical charts and compared with administrative data. Code combinations and algorithms were used to improve the accuracy of administrative data.

Results

A total of 436 patients were identified. The accuracy of algorithms combining tumour location and type of operation for right colon, left colon and rectum were 93, 89 and 88%, respectively. The accuracy of histological type was 89%, lymph node status 92% and metastasis status 88%. The accuracy of return to theatre and in‐hospital mortality was 100%.

Conclusion

Administrative data can provide reliable information on tumour details and short‐term post‐operative outcomes. The potential for administrative data to validate data captured in registries and be used independently for audit and research should be further explored.

     

Prospective study of robotic partial nephrectomy for renal cancer in Japan: Comparison with a historical control undergoing laparoscopic partial nephrectomy

Objectives

To evaluate the outcomes of robotic partial nephrectomy compared with those of laparoscopic partial nephrectomy for T1 renal tumors in Japanese centers.

Methods

Patients with a T1 renal tumor who underwent robotic partial nephrectomy were eligible for inclusion in the present study. The primary end‐point consisted of three components: a negative surgical margin, no conversion to open or laparoscopic surgery and a warm ischemia time ≤25 min. We compared data from these patients with the data from a retrospective study of laparoscopic partial nephrectomy carried out in Japan.

Results

A total of 108 patients were registered in the present study; 105 underwent robotic partial nephrectomy. The proportion of patients who met the primary end‐point was 91.3% (95% confidence interval 84.1–95.9%), which was significantly higher than 23.3% in the historical data. Major complications were seen in 19 patients (18.1%). The mean change in the estimated glomerular filtration rate in the operated kidney, 180 days postoperatively, was ?10.8 mL/min/1.73 m² (95% confidence interval ?12.3–9.4%).

Conclusions

Robotic partial nephrectomy for patients with a T1 renal tumor is a safe, feasible and more effective operative method compared with laparoscopic partial nephrectomy. It can be anticipated that robotic partial nephrectomy will become more widely used in Japan in the future.

     

A New Intraoperative Syndesmosis Instability Classification System: Utility and Medium‐term Results in Closed Displaced Ankle Fractures

Objective

To investigate the utility and medium‐term results of a new intra‐operative classification system for distal tibiofibular syndesmosis injury in ankle fractures.

Methods

Between January 2010 and January 2015, 116 patients diagnosed with displaced closed Weber B and C ankle fractures were treated in our department. The etiology of injury was 56 cases of fall‐sprain, 36 of traffic injury, 14 of fall from a height, and 10 of multiple injuries. After fixation of the fibular fracture, we classify syndesmosis stability as either normal or one of three grades of instability using the fibular hook traction test. This determined further fixation selection and final syndesmosis treatment.

Results

Of 116 cases, 82 (71%) demonstrated a tibiofibular syndesmosis injury and 52 (45%) were unstable. Twenty‐six cases were type I injuries (<4 mm displacement), 41% cases were type II injuries (4–7 mm displacement), and 3% of cases were type III injuries (>7 mm displacement). Types II and III are defined as unstable and require stabilization. Type III injuries have multiplanar instability and require two screws at the syndesmosis. Weber C fractures demonstrate significantly greater degrees of instability than Weber B fractures (χ² = 15.50, P = 0.0014). All patients were followed up for 12–24 months, with no cases of non‐union or broken screws. Good and excellent results were achieved in 93% of cases (according to the American Orthopaedic Foot and Ankle Society scoring system).

Conclusion

The syndesmosis instability classification system provides a rational and efficient basis for managing syndesmosis instability. Our results from application of the algorithm justify its further evaluation in the treatment of patients with closed displaced Weber B and C ankle fractures.

     

The efficacy and safety of cold‐induced lipolysis in the treatment of pseudogynecomastia

Background

The treatment options for pseudogynecomastia have been limited. Cold‐induced lipolysis provides a noninvasive, localized subcutaneous adipocyte destruction by inducing adipocyte apoptosis.

Objective

This study has been designed to evaluate the efficacy of cold‐induced lipolysis as a treatment modality for pseudogynecomastia.

Methods

In this 28‐week prospective trial, a total of 12 male pseudogynecomastia patients (Korean) were treated twice with cold‐induced lipolysis. Efficacy was determined by chest circumference, ultrasonographic measurement of fat thickness, Simon's Gynecomastia class (SGC), photographic assessment, and the patient's satisfaction (baseline, weeks 4, 8, 16, and 28). Using a questionnaire, safety was evaluated at each visit.

Results

For 10 subjects that completed the trial, chest circumference and fat thickness significantly improved by week 8. This same improvement was gradually noticed through week 28. The patients SGC scores continuously decreased after two sessions. Photographic assessment showed an improvement until week 28. The result of the patient's satisfaction score was also meaningful. While there were no adverse events observed, transient pain and bruising at the treatment site were noticed.

Limitations

We recruited a limited number of participants. Also, we could not exclude there might be other individual factors in association with the patients pseudogynecomastia.

Conclusion

Cold‐induced lipolysis is a safe, effective therapeutic option in the treatment of pseudogynecomastia. Lasers Surg. Med. 48:584–589, 2016. © 2016 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals Inc.

     

Laparoscopic adrenalectomy using the lateral retroperitoneal approach: Is it a safe and feasible treatment option for pheochromocytomas larger than 6 cm?

Objectives

To evaluate the surgical feasibility of laparoscopic adrenalectomy using the lateral retroperitoneal approach for the treatment of large pheochromocytomas, and to identify the preoperative risk factors for intraoperative hypertension.

Methods

We retrospectively reviewed 51 patients who underwent laparoscopic adrenalectomy using the lateral retroperitoneal approach for the treatment of pheochromocytomas. Patient characteristics and perioperative outcomes were analyzed and compared between the two study groups based on tumor size: group A (n = 27, ≤6 cm) and group B (n = 24, ?6 cm).

Results

There was no significant difference in preoperative characteristics between the two groups except for tumor size (P = 0.001) and urinary metanephrine (P = 0.011). Group B patients required longer operating time (P = 0.008), had a greater estimated blood loss (P = 0.001) and hemoglobin change (P = 0.002). However, no significant differences were observed in perioperative complications and mortality. Multivariate analysis showed that symptomatic pheochromocytomas (P = 0.004) and tumor size (P = 0.007) were significant risk factors for intraoperative hypertension.

Conclusions

Laparoscopic adrenalectomy using the lateral retroperitoneal approach for pheochromocytomas can be regarded as a treatment option, even for tumors measuring >6 cm. Symptomatic pheochromocytomas and large tumor size seem to represent risk factors for intraoperative hypertension.

     

Effect of requiring a general practitioner at scenes of serious injury: A systematic review

Background

In Norway, each municipality is responsible for providing first line emergency healthcare, and it is mandatory to have a primary care physician/general practitioner on call continuously. This mandate ensures that a physician can assist patients and ambulance personnel at the site of severe injuries or illnesses. The compulsory presence of the general practitioner at the scene could affect different parts of patient treatment, and it might save resources by obviating resources from secondary healthcare, like pre‐hospital anaesthesiologists and other specialized resources. This systematic review aimed to examine how survival, time spent at the scene, the choice of transport destination, assessment of urgency, the number of admissions, and the number of cancellations of specialized pre‐hospital resources were affected by the presence of a general practitioner at the scene of a suspected severe injury.

Methods

We searched for published and planned systematic reviews and primary studies in the Cochrane Library, Medline, Embase, OpenGrey, GreyLit and trial registries. The search was completed in December 2017. Two individuals independently screened the references and assessed the eligibility of all potentially relevant studies.

Results

The search for systematic reviews and primary studies identified 5981 articles. However, no studies met the pre‐defined inclusion criteria.

Conclusion

No studies met our inclusion criteria; consequently, it remains uncertain how the presence of a general practitioner at the injury scene might affect the selected outcomes.

     

A two‐drug combination simulation study for metastatic castrate resistant prostate cancer

Background

Prostate cancer often evolves resistance to androgen deprivation therapy leading to a lethal metastatic castrate‐resistant form. Besides androgen independence, subpopulations of the tumor are genetically heterogeneous. With the advent of tumor genome sequencing we asked which has the greater influence on reducing tumor size: genetic background, heterogeneity, or drug potency?

Methods

A previously developed theoretical evolutionary dynamics model of stochastic branching processes is applied to compute the probability of tumor eradication with two targeted drugs. Publicly available data sets were surveyed to parameterize the model.

Results

Our calculations reveal that the greatest influence on successful treatment is the genetic background including the number of mutations overcoming resistance. Another important criteria is the tumor size at which it is still possible to achieve tumor eradication, for example, 2‐4 cm large tumors have at best a 10% probability to be eradicated when 50 mutations can confer resistance to each drug.

Conclusion

Overall, this study finds that genetic background and tumor heterogeneity are more important than drug potency in treating mCRPC. It also points toward identifying metastatic sites early using biochemical assays and/or dPET.

     

Combination of solifenacin with tamsulosin reduces prostate volume and vascularity as opposed to tamsulosin monotherapy in patients with benign prostate enlargement and overactive bladder symptoms: Results from a randomized pilot study

Objectives

To identify the potential influence of antimuscarinics on morphometric parameters of the prostate in patients with benign prostatic enlargement and overactive bladder.

Methods

Non‐neurological patients with prostate volume >30 mL, predominately storage lower urinary tract symptoms, three or more urgency episodes per 24 h, maximum flow rate ≥10 mL/s and post‐void residual ≤100 mL were recruited for this study. They were randomized to receive either tamsulosin or tamsulosin + solifenacin. Patients were submitted to transrectal and transvesical ultrasonography, pressure‐flow study and prostate‐specific antigen test, and completed the International Prostate Symptom Score, bladder diary and overactive bladder questionnaire at induction and at 6 months. End‐study changes in morphometric prostate parameters (total prostate and adenoma volumes, prostate vascularity), as measured by transrectal ultrasound, were the principal outcomes.

Results

A reduction in total prostate volume (mean ?9.5%) was noted in the combination group, as opposed to an increase in the monotherapy group (+9.2%; P < 0.001). Similar changes were reflected in adenoma volume (monotherapy +17.4% vs combination ?12.5%, P = 0.001) and in prostate vascularity (monotherapy +149.3% vs combination ?19.8%, P = 0.001). Both treatment regimens improved the International Prostate Symptom Score (P = 0.001); monotherapy improved the voiding subscale (P = 0.01) more, whereas combination therapy improved the storage subscale (P = 0.024). Cystometric capacity improved in the combination group (P < 0.001). Post‐void residual was increased in the combination group (+34.79%), as opposed to a decrease in the monotherapy group (?17.05%; P = 0.001).

Conclusions

The results of this pilot study suggest that solifenacin might affect morphometric properties of the prostate, decreasing total prostate and adenoma volume, as well as vascularity. A molecular effect of antimuscarinics on the prostate, in parallel with their expected bladder effect, warrants further investigation.