Heterogeneity In Patient Selection Research Articles

Surgical decisions on implant-related parameters can enhance knowledge transfer for glenoid bone grafting in primary reverse shoulder arthroplasty: a scoping review of heterogeneity sources.

The purpose of the present scoping review is to identify sources of heterogeneity in reporting domains that have the potential to improve surgical decision-making in reverse shoulder arthroplasty associated with glenoid bone grafting. A scoping review was conducted according to the JBI and PRISMA ScR guidelines. Articles covering glenoid bone grafting at the time of reverse shoulder replacement, published between 2012 and 2022 in MEDLINE, Scopus, Epistemonikos, Web of Science, and Cochrane Database of Systematic Reviews, were searched. Reporting of core outcome measures, as well as prosthesis-related variables, rehabilitation protocols, radiographic evaluation methods, and bone graft incorporation assessments, were collected. For the final analysis, a total of 14 articles were considered. There were 649 operated shoulders with a mean patient age of 72 years, ranging from 48 to 85 years. Analysis of preoperative ranges of motion and patient-reported outcome measures revealed increased heterogeneity in patient selection between studies. Reporting of implant-related parameters was the most inconsistent. Rehabilitation protocols were scarcely reported. Assessment of graft incorporation and radiographic evaluation of choice revealed that there is no consistent method or measurement and the clinical relevance of radiolucent lines at the graft-glenoid bone interface is unclear. Addressing implant-related reporting gaps has the highest potential to improve surgical decision-making and provide orthopedic surgeons with a more comprehensive understanding of published results on glenoid bone grafting at the time of primary reverse shoulder arthroplasty.

The clinical signification and application value of [68Ga]Ga-PSMA imaging in thyroid malignancy.

Approximately 5% of differentiated thyroid cancers lose the ability to uptake iodine, leading to limited treatment options and poor prognosis due to invasion and distant metastasis. PSMA imaging probes have been proposed as a potential diagnostic and therapeutic tool for iodine-refractory thyroid cancer. However, there are limited reports and significant heterogeneity in patient selection, warranting further exploration of the application value of PSMA in thyroid cancer. We performed Western Blot, PCR, and [68Ga]Ga-PSMA uptake experiments on cell lines and conducted in vivo small animal imaging. Clinical and radiological results of included differentiated thyroid cancer patients were collected. (Trial registration number: 2021-669, Trial registration date: December 30, 2021). PSMA expression levels were significantly higher in poorly differentiated thyroid cancer (7.86 ± 1.90 vs. 1.00 ± 0, P < 0.01; 7.86 ± 1.90 vs. 0.03 ± 0.02, P < 0.01), but [68Ga]Ga-PSMA imaging correlated with tumor burden, such as 18F-FDG (8.08 ± 7.74 and 5.67 ± 4.23, P = 0.01) and Tg levels (307.1 ± 183.4 vs. 118.0 ± 116.1, P = 0.002). Our results showed that PSMA expression increased with the decrease of thyroid cancer differentiation. However, the level of [68Ga]Ga-PSMA uptake in thyroid cancer patients was not significantly associated with the degree of thyroid cancer differentiation, but also with the metabolism and burden of tumors such as 2-[18F]FDG and Tg levels. These findings provide additional clinical significance and application value for PSMA in thyroid cancer.

Development of an app-based bedside clinical decision-making tool for mechanical cardiocirculatory support in patients with cardiogenic shock: the MCS-Aid app

Abstract Background Patients presenting with cardiogenic shock remain at high risk of morbidity and mortality. Several mechanical cardiocirculatory support (MCS) devices have been developed and their use is rapidly increase in clinical practice. However, there is significant heterogeneity in patient selection, timing of implantation, and post-implantation management across centers and operators. Purpose We sought to develop and smartphone app-based clinical decision-making tool to help bedside selection and post-implantation management of MCS devices in patients presenting with cardiogenic shock or cardiac arrest. Methods The MCS-Aid app will consistent of 3 major sections: (i) initial device selection based on clinical presentation (patients with cardiogenic shock or cardiac arrest post-ROSC); (ii) guide for escalation or addition of MCS based on the individual hemodynamic scenario; (iii) guide for weaning after implantation of MCS device. The app will have an interactive interface that will allow the user to select the most appropriate next step in management based on the clinical information being entered. A calculator to derive key hemodynamic parameters (e.g. cardiac power output or pulmonary artery pulsatility index) will be incorporated in the App to inform clinical decision-making when appropriate. An example of an algorithm that will be part of the MCS-Aid app is illustrated in the figure. Conclusions The MCS-Aid app is an user-friendly bedside clinical decision tool that could help fellows-in-training, early-career interventionalist and interventional cardiologist to select the appropriate MCS device according to the individual clinical and hemodynamic scenario. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Abiomed

Development of an app-based bedside clinical decision-making tool for mechanical cardiocirculatory support in patients with cardiogenic shock: the MCS-Aid app

Abstract Background Patients presenting with cardiogenic shock remain at high risk of morbidity and mortality. Several mechanical cardiocirculatory support (MCS) devices have been developed and their use is rapidly increase in clinical practice. However, there is significant heterogeneity in patient selection, timing of implantation, and post-implantation management across centers and operators. Purpose We sought to develop and smartphone app-based clinical decision-making tool to help bedside selection and post-implantation management of MCS devices in patients presenting with cardiogenic shock or cardiac arrest. Methods The MCS-Aid app will consistent of 3 major sections: (i) initial device selection based on clinical presentation (patients with cardiogenic shock or cardiac arrest post-ROSC); (ii) guide for escalation or addition of MCS based on the individual hemodynamic scenario; (iii) guide for weaning after implantation of MCS device. The app will have an interactive interface that will allow the user to select the most appropriate next step in management based on the clinical information being entered. A calculator to derive key hemodynamic parameters (e.g. cardiac power output or pulmonary artery pulsatility index) will be incorporated in the App to inform clinical decision-making when appropriate. An example of an algorithm that will be part of the MCS-Aid app is illustrated in the figure. Conclusions The MCS-Aid app is an user-friendly bedside clinical decision tool that could help fellows-in-training, early-career interventionalist and interventional cardiologist to select the appropriate MCS device according to the individual clinical and hemodynamic scenario. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Abiomed

825 Local Excision Versus Total Mesorectal Excision Following Neoadjuvant Chemoradiotherapy for Rectal Cancer. a Systematic Review and Meta-Analysis

Abstract Aim Total mesorectal excision with or without neoadjuvant chemoradiotherapy remains the gold standard treatment for rectal cancer. This systematic review aims to establish if Local Excision (LE) in conjunction with neoadjuvant therapy can be used to improve morbidity and functional outcomes without significantly impacting oncological outcomes. Method A systematic review and meta-analysis was performed using the PRISMA guidelines. All studies comparing neoadjuvant chemoradiotherapy and local excision versus TME were included from 2000 to 2020. Primary endpoint included local recurrence rates. Secondary outcomes included distant recurrence, disease free survival and overall survival. Subgroup analysis was performed on randomised control trials (RCT). Results Of the 9 studies included, 2 were RCTs. A total of 1161 patients underwent neoadjuvant chemoradiotherapy and surgical excision (LE n=252, TME n=909). Local recurrence was 10% in the LE group compared to 7% in the TME group (OR 0.60, 95% CI 0.33–1.09, p=0.09). Furthermore, there was no significant difference in distant metastasis (OR 1.37, 95% CI 0.84–2.26, p=0.21), Disease Free Survival (DFS) (OR 1.08, 95% CI 0.65–1.82, p=0.76) or Overall Survival (OS) (OR 1.14, 95% CI 0.56–2.35, p=0.71). In subgroup analysis of RCTs, local recurrence rates of 7.2% were seen in the LE group compared to 6.6% in the TME group (OR 0.90, 95% CI 0.34–2.43, p=0.84). Conclusions Neoadjuvant chemoradiotherapy and local excision is oncologically safe in select patients. A higher non-significant local recurrence rate was seen in the LE group; however, this may be due to heterogeneity in patient selection. Similar local recurrences and oncological outcomes were verified in the RCTs.

Stereotactic Body Radiation Therapy (SBRT) for Oligorecurrent/Oligoprogressive Mediastinal and Hilar Lymph Node Metastasis: A Systematic Review.

Simple SummaryThis paper is a review of the literature on oligorecurrent/oligoprogressive mediastinal and hilar lymph node metastasis treated with SBRT. The use of mediastinal SBRT had historically been not feasible in view of the expected toxicity due to the proximity of critical structures such as the airways and esophagus. Despite the heterogeneity and lack of some data in the studies analyzed, this literature review is the first published and can be a valid guide for the radiotherapist in the management of oligometastatic/oligoprogressive patients, with particular regard to the radiotherapy doses, dose constraints for organs at risk, and clinical outcomes.Introduction: Mediastinal or hilar lymph node metastases are a challenging condition in patients affected by solid tumors. Stereotactic body radiation therapy (SBRT) could play a crucial role in the therapeutic management and in the so-called “no-fly zone”, delivering high doses of radiation in relatively few treatment fractions with excellent sparing of healthy surrounding tissues and low toxicity. The aim of this systematic review is to evaluate the feasibility and tolerability of SBRT in the treatment of mediastinal and hilar lesions with particular regard to the radiotherapy doses, dose constraints for organs at risk, and clinical outcomes. Materials and methods: Two blinded investigators performed a critical review of the Medline, Web of Knowledge, Google Scholar, Scopus, and Cochrane databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA), starting from a specific question: What is the clinical impact of SBRT for the treatment of oligorecurrent/oligoprogressive mediastinal and hilar metastasis? All retrospective and prospective clinical trials published in English up to February 2022 were analyzed. Results: A total of 552 articles were identified and 12 of them were selected with a total number of 478 patients treated with SBRT for mediastinal or hilar node recurrence. All the studies are retrospective, published between 2015 and 2021 with a median follow-up ranging from 12 to 42.2 months. Studies following SBRT for lung lesions or retreatments after thorax radiotherapy for stage III lung cancer were also included. The studies showed extensive heterogeneity in terms of patient and treatment characteristics. Non-small cell lung cancer was the most frequently reported histology. Different dose schemes were used, with a higher prevalence of 4–8 Gy in 5 or 6 fractions, but dose escalation was also used up to 52 Gy in 4 fractions with dose constraints mainly derived from RTOG 0813 trial. The radiotherapy technique most frequently used was volumetric modulated arc therapy (VMAT) with a median PTV volume ranging from 7 to 25.7 cc. The clinical outcome seems to be very encouraging with 1-year local control (LC), overall survival (OS) and progression-free survival (PFS) rates ranging from 84 to 94%, 53 to 88% and 23 to 53.9%, respectively. Half of the studies did not report toxicity greater than G3 and only five cases of fatal toxicity were reported. CONCLUSIONS: From the present review, it is not possible to draw definitive conclusions because of the heterogeneity of the studies analyzed. However, SBRT appears to be a safe and effective option in the treatment of mediastinal and hilar lymph node recurrence, with a good toxicity profile. Its use in clinical practice is still limited, and there is extensive heterogeneity in patient selection and fractionation schedules. Good performance status, small PTV volume, absence of previous thoracic irradiation, and administration of a high biologically effective dose (BED) seem to be factors that correlate with greater local control and better survival rates. In the presence of symptoms related to the thoracic lymph nodes, SBRT determines a rapid control that lasts over time. We look forward to the prospective studies that are underway for definitive conclusions.

Clinical Profile, Outcomes, and Complications in Neonates Undergoing Peritoneal Dialysis in a Tertiary Neonatal Care Unit - An Observational Study.

Peritoneal dialysis (PD) is the most common form of renal replacement therapy in neonates and there is a lot of heterogeneity in patient selection and outcomes across the various units. This study aimed to assess the indications, complications, and outcomes in terms of survival of PD. This is a retrospective study of 23 neonates who underwent acute PD at a tertiary care neonatal unit between August 2016 and July 2021. A cross-sectional poll was also conducted among the doctors who have been in the unit for the past 10 years regarding their experience in PD. The baseline, clinical, biochemical parameters, outcomes, and complications were analyzed. All statistical analyses were performed using the IBM SPSS Statistics version 23.0 software. The mean (±standard deviation) gestational age and birth weights of neonates were 32.6 ± 4 weeks and 1743 ± 922 g, respectively. Six (26%) babies had extremely low birth weight, five (22%) very low birth weight (VLBW), and seven (30%) low birth weight. The indications were acute kidney injury [17/23 (74%)], fluid overload [3/23 (17%)], suspected inborn errors of metabolism [2/23 (9%)] and hypernatremia [1/23 (4%)]. A pigtail catheter (74%) was used in most of them. Catheter block was noticed in four babies and peritonitis in two neonates. We did not encounter any complications during the procedure, and PD appears to be practicable across all gestational ages and birth weights.

Primary mobile vertebral column sarcomas: Prognostic factors vary by histologic subtypes.

Primary sarcomas originating from the mobile spine portends a particularly sinister outcome. Rarity of the disease process has resulted in inconsistent data due to small sample size and heterogeneity in patient selection and analytics. Surveillance, Epidemiology and End Result (SEER) database from 1975 to 2017 was queried to report incidence and survival data in 712 patients in the United States. Kaplan-Meier and Cox Regression were used to determine the prognostic factors affecting survival. Incidence of spinal sarcoma was 0.019 per 100,000 persons in 2017 and has not significantly changed since 2000 (p > 0.05). Disease-specific 5-year survival for the entire cohort was 57%. Osteosarcoma has the worst 5-year survival (39%) and chondrosarcoma has the best 5-year survival (69%). Independent predictors of survival for the entire cohort included age, grade, and stage. Stage was an independent predictor of survival for every histologic subtype. Additional predictors of survival for spinal osteosarcoma, Ewing sarcoma, and chondrosarcoma included age, size, and grade, respectively. The current study is an analysis of a population-based registry reporting incidence survival data for patients with sarcoma of mobile vertebral column. Survival and prognostic factors vary by histologic subtypes. There is lack of improvement in survival over the last three decades.

Omics analyses in peritoneal metastasis-utility in the management of peritoneal metastases from colorectal cancer and pseudomyxoma peritonei: a narrative review.

High-throughput "-omics" analysis may provide a broader and deeper understanding of cancer biology to define prognostic and predictive biomarkers and identify novel therapy targets. In this review we provide an overview of studies where the peritoneal tumor component of peritoneal metastases from colorectal cancer (PM-CRC) and pseudomyxoma peritonei (PMP) were analyzed. Most of the available data was derived from DNA mutation analysis, but a brief review of findings from transcriptomic and protein expression analysis was also performed. Studies reporting genomic analysis of peritoneal tumor samples from 1,779 PM-CRC and 623 PMP cases were identified. The most frequently mutated genes in PM-CRC were KRAS, APC, SMAD4, BRAF, and PIK3CA, while in PMP KRAS, GNAS, FAT4, TGFBR1, TP53 and SMAD3/4 mutations were most commonly identified. Analyses were performed by single-gene analyses and to some extent targeted next-generation sequencing, and a very limited amount of broad explorative data exists. The investigated cohorts were typically small and heterogeneous with respect to the methods used and to the reporting of clinical data. This was even more apparent regarding transcriptomic and protein data, as the low number of cases examined and quality of clinical data would not support firm conclusions. Even for the most frequently mutated genes, the results varied greatly; for instance, KRAS mutations were reported at frequencies between 20-57% in PM-CRC and 38-100% in PMP. Such variation could be caused by random effects in small cohorts, heterogeneity in patient selection, or sensitivity of applied technology. Although a large number of samples have been subjected to analysis, cross-study comparisons are difficult to perform, and combined with small cohorts and varying quality and detail of clinical information, the observed variation precludes useful interpretation in a clinical context. Although omics data in theory could answer questions to aid management decisions in PM-CRC and PMP, the existing data does not presently support clinical implementation. With the necessary technologies being generally available, the main challenge will be to obtain sufficiently large, representative cohorts with adequate clinical data and standardized reporting of results. Importantly, studies where the focus is specifically on peritoneal disease are needed, where the study designs are aligned with clearly defined research questions to allow robust conclusions. Such studies are highly warranted if patients with PM-CRC and PMP are to derive benefit from recent advances in precision cancer medicine.

Regenerative Treatment of Peri-Implantitis: A Systematic Revie.

Objectives:The aim of this systematic review was to assess the clinical efficacy of bone regeneration for treatment of peri-implantitis.Materials and Methods:Electronic search of the literature was performed to identify randomized clinical trials (RCTs) and case series on treatment of peri-implantitis using bone regeneration procedures with at least 6 months of follow-up. The guidelines of the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) were applied. The risk of bias was assessed using the Cochrane Collaboration’s Risk of Bias tool.Results:Two RCTs and 16 case series with a total of 520 treated patients (2002 implants) were included. Bone regenerative procedures showed controversial results regarding bone fill. Two studies reported statistically significant bone gain while four studies reported insignificant bone gain. Other studies reported bone gain with no P value. Pocket depth (PD) reduction varied among the studies since four studies reported a significant reduction in PD while four others reported insignificant reduction in PD. Other studies reported a reduction in PD with no P value. Bone regeneration procedures seemed to decrease bleeding on probing (BOP) but they did not seem conducive to increase the width of keratinized gingiva. Increased keratinized gingiva was noted in cases with subepithelial grafts.Conclusion:Evaluation of the effectiveness of bone regeneration techniques in this systematic review presented limitations related to heterogeneity in patient selection (age, history of periodontitis, smoking status and implant system), means of disinfection and decontamination, and variability of the materials used for treatment.

A systematic review of salvage focal therapies for localised non-metastatic radiorecurrent prostate cancer.

Although radiotherapy to the prostate for cancer is effective, recurrence occurs in 10–15% within 5 years. Traditional salvage treatments for men with radiorecurrent prostate cancer comprise of watchful waiting (WW) with or without androgen deprivation therapy (ADT) or radical prostatectomy (RP). Neither strategy provides ideal therapeutic ratios. Salvage focal ablation is an emerging option. We performed a systematic review of the Medline and Embase databases for studies reporting outcomes of focal salvage brachytherapy (sBT), cryotherapy (sCT) or high-intensity focused ultrasound (sHIFU) for radiorecurrent prostate cancer (conception to April 2019). Results were screened for inclusion against predetermined eligibility criteria. Certain data were extracted, including rates of biochemical disease-free survival (BDFS), metastasis, conversion to second-line therapies and adverse events. Of a total 134 articles returned from the search, 15 studies (14 case series and 1 comparative study) reported outcomes after focal sBT [5], sCT [7] and sHIFU [3]. Cohort size varied depending on intervention, with eligible studies of sBT being small case series. Median follow-up ranged from 10 to 56 months. Although pre-salvage demographics were similar [median age range, 61–75 years; prostate-specific antigen (PSA) range, 2.8–5.5 ng/mL], there was heterogeneity in patient selection, individual treatment protocols and outcome reporting. At 3 years, BDFS ranged from 61% to 71.4% after sBT, 48.1–72.4% after sCT and 48% after sHIFU. Only studies of sCT reported 5-year BDFS, which ranged from 46.5% to 54.4%. Rates of metastasis were low after all salvage modalities, as were conversion to second-line therapies (although this was poorly reported). Grade 3 adverse events were rare. This systematic review indicates that salvage focal ablation of radiorecurrent prostate cancer provides acceptable oncological outcomes and is well tolerated. Unfortunately, there is heterogeneity in the study design of existing evidence. Level 1 research comparing salvage focal therapies to existing whole-gland strategies is needed to further establish the role of these promising treatments.

Charcot foot reconstruction outcomes: A systematic review

BackgroundCharcot neuroarthropathy is a complex condition characterised by progressive deformity, limited treatment options and a high amputation rate. Surgical reconstruction of Charcot foot has been proposed as a method to preserve the foot. However, limited information exists on the different methods of reconstruction available, their outcomes and complications. MethodsWe systematically analysed published data from Jan 1993 to Dec 2018 to assess methods of fixation and associated outcomes for the surgical reconstruction in Charcot neuroarthropathy. Statistical analyses were undertaken to determine the amputation rates, return to ambulation and complications associated with these techniques. ResultsA total of 1116 feet (1089 patients) were reported to have undergone reconstruction with significant heterogeneity in patient selection. Of these, 726 (65%) were reported to undergo internal fixation, 346 feet (31%) external fixation and 44 (4%) undergoing simultaneous internal and external fixation. No single technique demonstrated a significant benefit over the other. Overall, the bone fusion rate was 86.1%. Complications directly attributable to the technique employed were noted in 36% of individuals. The reported post-reconstruction amputation rate was only 5.5% with 91% apparently returning to ambulation. ConclusionsAlthough no preferential method of fixation was identified, we find that the current options for surgical reconstruction could offer limb salvage with a low amputation risk in a highly selected population. However, the lack of controlled studies, inconsistent reporting of outcomes and heterogeneity of patient selection mean that the quality of evidence is low.

A historical cohort of temporal lobe surgery for medically refractory epilepsy: a systematic review and meta-analysis to guide future nonrandomized controlled trial studies.

Recent trials for temporal lobe epilepsy (TLE) highlight the challenges of investigating surgical outcomes using randomized controlled trials (RCTs). Although several reviews have examined seizure-freedom outcomes from existing data, there is a need for an overall seizure-freedom rate estimated from level I data as investigators consider other methods besides RCTs to study outcomes related to new surgical interventions. The authors performed a systematic review and meta-analysis of the 3 RCTs of TLE in adults and report an overall surgical seizure-freedom rate (Engel class I) composed of level I data. An overall seizure-freedom rate was also collected from level II data (prospective cohort studies) for validation. Eligible studies were identified by filtering a published Cochrane meta-analysis of epilepsy surgery for RCTs and prospective studies, and supplemented by searching indexed terms in MEDLINE (January 1, 2012-April 1, 2018). Retrospective studies were excluded to minimize heterogeneity in patient selection and reporting bias. Data extraction was independently reverified and pooled using a fixed-effects model. The primary outcome was overall seizure freedom following surgery. The historical benchmark was applied in a noninferiority study design to compare its power to a single-study cohort. The overall rate of seizure freedom from level I data was 72.4% (55/76 patients, 3 RCTs), which was nearly identical to the overall seizure-freedom rate of 71.7% (1325/1849 patients, 18 studies) from prospective cohorts (z = 0.134, p = 0.89; z-test). Seizure-freedom rates from level I and II studies were consistent over the years of publication (R2 < 0.01, p = 0.73). Surgery resulted in markedly improved seizure-free outcomes compared to medical management (RR 10.82, 95% CI 3.93-29.84, p < 0.01; 2 RCTs). Noninferiority study designs in which the historical benchmark was used had significantly higher power at all difference margins compared to using a single cohort alone (p < 0.001, Bonferroni's multiple comparison test). The overall rate of seizure freedom for temporal lobe surgery is approximately 70% for medically refractory epilepsy. The small sample size of the RCT cohort underscores the need to move beyond standard RCTs for epilepsy surgery. This historical seizure-freedom rate may serve as a useful benchmark to guide future study designs for new surgical treatments for refractory TLE.

Trochleoplasty provides good clinical outcomes and an acceptable complication profile in both short and long-term follow-up.

The purpose of this study is to report on the global distribution and clinical outcomes of published articles related to trochleoplasty. The online databases OVID Medline, OVID EMBASE, and the Cochrane Library were searched for the literature assessing trochleoplasty performed for lateral patellofemoral instability (LPI). Study data were abstracted looking at global trends in the literature, as well as clinical and patient-reported outcomes following this technique. For the assessment of global distribution, 29 studies including 998 patients met the inclusion criteria. The majority of the studies were conducted in Europe (93%) and most used an open thin flap technique (52%). For the secondary analysis of clinical outcomes, 21 studies were included with significant heterogeneity in patient selection, reporting on the degree of trochlear dysplasia, and patient-reported outcomes. All trochleoplasty techniques showed statistically significant improvement in clinical outcomes at average 50 months (range 3-228 months) post-operative, with most patients being satisfied with their procedure. Re-dislocation and complication rates were low. European centers have published majority of data on trochleoplasty surgery, which has been shown to be an acceptable procedure for patients with high-grade trochlear dysplasia and LPI. Trochleoplasty has demonstrated good clinical outcomes, a low re-dislocation rate, and an acceptable complication profile in both short and long-term follow-up. This study highlights the difficulty in reporting outcomes in this group of patients due to heterogeneity in patient selection, grading of trochlear dysplasia, and the lack of disease-specific outcome measures. IV.

Ablation energies for focal treatment of prostate cancer

ContextIn recent years, focal therapy has emerged as a treatment option for a selected group of men with localized prostate cancer. Cryotherapy and high-intensity focused ultrasound (HIFU) are the most investigated types of focal treatment with other options currently under evaluation.ObjectiveThe objective of the study was to give a comprehensive overview of six available focal treatment options for prostate cancer with their rationale, delivery mechanism, and outcomes.Information acquisitionThe SIU ICUD chapter on available Energies to Treat Prostate Cancer was used as a guide to describe the different technologies. For outcomes, a literature search was conducted using PubMed key words including focal therapy, HIFU, cryotherapy, irreversible electroporation, vascular-targeted photodynamic therapy, laser interstitial therapy, radiofrequency ablation, microwave therapy, and their synonyms in MeSH terms.ConclusionFocal therapy appears to have encouraging outcomes on quality of life and urinary and erectile function. For oncological outcomes, it is challenging to fully interpret the outcomes due to heterogeneity in patient selection and short-term follow-up.

The effectiveness of low-dose and high-dose tranexamic acid in posterior lumbar interbody fusion: a double-blinded, placebo-controlled randomized study.

Tranexamic acid is a proven drug used for reduction of intraoperative blood loss in spinal surgery. However, optimal dosing considering risk/benefits is not well established owing to the heterogeneity in patient selection and surgical procedures of previous studies. This study aimed to evaluate the effectiveness and safety of various tranexamic acid regimens in reducing perioperative blood loss in single-level posterior lumbar interbody fusion (PLIF). Patients were randomly grouped into three different interventions: low-dose tranexamic acid (LD), high-dose tranexamic acid (HD), and placebo-controlled (PC) groups. The HD and LD groups received 10 and 5mg/kg of bolus loading dose and 2 and 1mg/kg of continuous infusion until 5h after surgery, respectively. Data on patient demographics and preoperative and 24-h postoperative laboratory values were collected. Outcome parameters include intraoperative blood loss, 24-h postoperative blood loss, and blood loss during removal of the last drain. Seventy-two patients (mean age 63.3±7.6years) showed similar baseline characteristics. Intraoperatively, blood loss was reduced by the administration of tranexamic acid (P=0.04), contributed predominantly by a difference between the LD and HD groups (123mL; P<0.01). The 24-h postoperative blood loss was reduced (P<0.01), contributed predominantly by a difference between the PC and LD groups (144mL; P=0.02). During the removal of the last drain, statistical difference was found between the PC and HD groups (125mL; P=0.00). No complications or side effects from tranexamic acid use were noted. Tranexamic acid administration for single-level PLIF was effective and safe in reducing perioperative blood loss in a dose-dependent manner. An HD regimen comprising 10mg/kg of bolus loading dose and 2mg/kg/h of continuous infusion is recommended. Level 1 study according to Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence.

Survey of current practices from the International Stereotactic Body Radiotherapy Consortium (ISBRTC) for head and neck cancers.

To provide a multi-institutional description of current practices of stereotactic body radiotherapy (SBRT) for head and neck cancer. 15 international institutions with significant experience in head and neck SBRT were asked to complete a questionnaire covering clinical and technical factors. SBRT is used 10-100% of the time for recurrent primary head and neck cancer, and 0-10% of the time in newly diagnosed disease. Five centers use a constraint for primary disease of 3-5 cm and 25-30 cc. Nine institutions apply a clinical target volume expansion of 1-10 mm and 14 use a planning target volume margin of 1-5 mm. Fractionation regimens vary between 15 and 22 Gy in 1 fraction to 30-50 Gy in 5 or 6 fractions. The risk of carotid blowout quoted in the re-irradiation setting ranges from 3 to 20%. There is considerable heterogeneity in patient selection and techniques in head and neck SBRT practice among experienced centers.

Immune-Enhancing Diets: What is the Final Answer?

Supplementation of certain micronutrients to standard nutrition therapy in pharmacological doses can modulate the host immunologic response. The three most extensively studied: arginine, glutamine, and omega-3 fatty acids (“fish oils”). While animal studies are encouraging, human clinical trials arrive at conflicting conclusions for multiple reasons, mainly related to heterogeneity in patient selection, concentration and combination of agents, dose, route, and timing and administration. Glutamine should not be given to patients with multi-organ (especially renal) failure and arginine should be avoided in septic shock. Enteral glutamine may be beneficial in burn and trauma patients. Larger, higher-quality studies are required before strong recommendations can be made.

Intraperitoneal chemotherapy as adjuvant treatment to prevent peritoneal carcinomatosis of colorectal cancer origin: a systematic review

Background:Peritoneal carcinomatosis (PC) of colorectal cancer (CRC) origin is associated with poor outcome. This systematic review evaluates the available evidence about adjuvant (hyperthermic) intraperitoneal chemotherapy ((H)IPEC) to prevent the development of PC.Methods:A systematic search of literature was conducted in August 2013 in PubMed, Embase, and the Cochrane database for studies on (H)IPEC to prevent PC in patients who underwent curative surgery for primary CRC.Results:Seven comparative studies and five cohort studies were selected. Treatment schedules varied between repeated fluoropyrimidine-based IPEC administration in the ambulatory setting to intra-operative (H)IPEC procedures using mitomycin-C or oxaliplatin. The reported rates of major complications related to adjuvant (H)IPEC was low. Four out of five evaluable comparative studies reported a significant difference in the incidence of PC in favour of (H)IPEC. All three comparative studies reporting on survival after intra-operative (H)IPEC showed a significant survival benefit in favour of the experimental arm. Substantial heterogeneity in patient selection, treatment protocols, and treatment effect evaluation among studies was observed.Conclusions:The currently available evidence about adjuvant (H)IPEC in high-risk CRC is limited and subject to bias, but points towards improved oncological outcome and supports further randomised studies.

Validation of Nomograms Predicting Lymph Node Involvement in Patients with Prostate Cancer Undergoing Extended Pelvic Lymph Node Dissection

Our aim was to validate Briganti's nomograms predicting the probability of lymph node involvement (LNI) in prostate cancer (PCa). Clinicopathological data of 256 PCa patients who underwent extended pelvic lymph node dissection (ePLND) and radical prostatectomy (RP) were obtained from two Bulgarian institutions. Predicted probabilities of LNI were assessed using Briganti's nomograms based on ePLND. In addition to the established basic LNI predictors, Briganti's nomograms included the number of lymph nodes removed (version 2006) and the number and percentage of positive biopsy cores (versions 2007 and 2012). The accuracy of these nomograms was compared with the updated Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram (version 2011). Receiver-operating characteristics analysis was done to assess the discriminative ability of each of the nomograms applied. All of Briganti's nomograms showed a higher predictive accuracy as compared with the updated MSKCC nomogram. The respective AUC values were calculated as 0.847, 0.837, 0.858 and 0.875 for the four Briganti nomograms, and 0.770 for the updated MSKCC nomogram, respectively. Despite the potential for heterogeneity in patient selection and management, all predictions demonstrated high concordance with actual observations. Compared with other similar prognostic tools the updated Briganti nomogram (version 2012) showed the highest predictive accuracy and should therefore be preferred.