A dosimetric analysis of rectal hydrogel spacer use in patients with recurrent prostate cancer undergoing salvage high-dose-rate brachytherapy.

PURPOSE: We hypothesize rectal hydrogel spacer (RHS) improves rectal dosimetry in patients undergoing salvage high-dose-rate brachytherapy (HDR-BT) for intact, recurrent prostate cancer (PC). METHODS AND MATERIALS: A prospectively collected institutional database was queried for recurrent PC patients treated with salvage HDR-BT from September 2015 to November 2021. Patients were offered RHS beginning June 2019. Dosimetric variables were compared between RHS and no-RHS groups for the average of two fractions using Wilcoxon rank-sum tests. Primary outcomes were rectal volume receiving 75% of prescription dose (V75%) and prostate volume receiving 100% of prescription dose (V100%). Generalized estimating equation (GEE) model was used to evaluate the association between other planning variables and rectal V75%. RESULTS: Forty-one PC patients received salvage HDR-BT, of whom 20 had RHS. All patients received 2400cGy in 2 fractions. Median RHS volume was 6.2cm3 (Standard deviation [SD]: ± 3.5cm3). Median follow-up was 4 months and 17 months in the RHS and no-RHS groups, respectively. Median rectal V75% with and without RHS were 0.0cm3 (IQR: 0.0-0.0cm3) and 0.06cm3 (IQR: 0.0-0.14cm3), respectively (p<0.001). Median prostate V100% with and without RHS were 98.55% (IQR: 97.86-99.22%) and 97.78% (IQR: 97.50-98.18%), respectively (p = 0.007). RHS, rectum, and prostate volumes did not significantly affect rectal V75% per GEE modeling. There was 10% G1-2 and 5% G3 rectal toxicity in RHS group. There was 9.5% G1-2 and no G3+ rectal toxicities in the no-RHS group. CONCLUSIONS: Absolute improvement in rectal V75% and prostate V100% was significant with RHS in PC patients undergoing salvage HDR-BT, but clinical benefit is marginal.

A Pragmatic Randomized Trial Comparing Surgical Clipping and Endovascular Treatment of Unruptured Intracranial Aneurysms.

BACKGROUND AND PURPOSE: Surgical clipping and endovascular treatment are commonly used in patients with unruptured intracranial aneurysms. We compared the safety and efficacy of the 2 treatments in a randomized trial. MATERIALS AND METHODS: Clipping or endovascular treatments were randomly allocated to patients with one or more 3- to 25-mm unruptured intracranial aneurysms judged treatable both ways by participating physicians. The study hypothesized that clipping would decrease the incidence of treatment failure from 13% to 4%, a composite primary outcome defined as failure of aneurysm occlusion, intracranial hemorrhage during follow-up, or residual aneurysms at 1 year, as adjudicated by a core lab. Safety outcomes included new neurologic deficits following treatment, hospitalization of >5 days, and overall morbidity and mortality (mRS > 2) at 1 year. There was no blinding. RESULTS: Two hundred ninety-one patients were enrolled from 2010 to 2020 in 7 centers. The 1-year primary outcome, ascertainable in 290/291 (99%) patients, was reached in 13/142 (9%; 95% CI, 5%-15%) patients allocated to surgery and in 28/148 (19%; 95% CI, 13%-26%) patients allocated to endovascular treatments (relative risk: 2.07; 95% CI, 1.12-3.83; P = .021). Morbidity and mortality (mRS >2) at 1 year occurred in 3/143 and 3/148 (2%; 95% CI, 1%-6%) patients allocated to surgery and endovascular treatments, respectively. Neurologic deficits (32/143, 22%; 95% CI, 16%-30% versus 19/148, 12%; 95% CI, 8%-19%; relative risk: 1.74; 95% CI, 1.04-2.92; P = .04) and hospitalizations beyond 5 days (69/143, 48%; 95% CI, 40%-56% versus 12/148, 8%; 95% CI, 5%-14%; relative risk: 0.18; 95% CI, 0.11-0.31; P < .001) were more frequent after surgery. CONCLUSIONS: Surgical clipping is more effective than endovascular treatment of unruptured intracranial aneurysms in terms of the frequency of the primary outcome of treatment failure. Results were mainly driven by angiographic results at 1 year.

Fracture incidence and fracture-related mortality decreased with decreases in population mobility during the early days of the COVID-19 pandemic: an epidemiological study.

INTRODUCTION: We investigated the impact of coronavirus disease 2019 (COVID-19) social distancing measures on fracture incidence and fracture-related mortality, as well as associations with population mobility. METHODS: In total, 47 186 fractures were analysed across 43 public hospitals from 22 November 2016 to 26 March 2020. Considering the smartphone penetration of 91.5% in the study population, population mobility was quantified using Apple Inc's Mobility Trends Report, an index of internet location services usage volume. Fracture incidences were compared between the first 62 days of social distancing measures and corresponding preceding epochs. Primary outcomes were associations between fracture incidence and population mobility, quantified by incidence rate ratios (IRRs). Secondary outcomes included fracture-related mortality rate (death within 30 days of fracture) and associations between emergency orthopaedic healthcare demand and population mobility. RESULTS: Overall, 1748 fewer fractures than projected were observed during the first 62 days of COVID-19 social distancing (fracture incidence: 321.9 vs 459.1 per 100 000 person-years, P<0.001); the relative risk was 0.690, compared with mean incidences during the same period in the previous 3 years. Population mobility exhibited significant associations with fracture incidence (IRR=1.0055, P<0.001), fracture-related emergency department attendances (IRR=1.0076, P<0.001), hospital admissions (IRR=1.0054, P<0.001), and subsequent surgery (IRR=1.0041, P<0.001). Fracture-related mortality decreased from 4.70 (in prior years) to 3.22 deaths per 100 000 person-years during the COVID-19 social distancing period (P<0.001). CONCLUSION: Fracture incidence and fracture-related mortality decreased during the early days of the COVID-19 pandemic; they demonstrated significant temporal associations with daily population mobility, presumably as a collateral effect of social distancing measures.

Long-Term Results of a Phase 3 Randomized Prospective Trial of Erectile Tissue-Sparing Intensity-Modulated Radiation Therapy for Men With Clinically Localized Prostate Cancer.

PURPOSE: The objective of this study was to determine whether limiting the doses delivered to the penile bulb (PB) and corporal bodies with intensity modulated radiation therapy (IMRT) preserves erectile function compared with standard IMRT in men with prostate cancer. METHODS AND MATERIALS: A total of 117 patients with low- to intermediate-risk, clinical T1a-T2c prostate adenocarcinoma were enrolled in a single-institution, prospective, single-blind, phase 3 randomized trial. All received definitive IMRT to 74 to 80 Gy in 37 to 40 fractions and standard IMRT (s-IMRT) or erectile tissue-sparing IMRT (ETS-IMRT), which placed additional planning constraints that limited the D90 to the penile bulb and corporal bodies to ≤15 Gy and ≤7 Gy, respectively. Erectile potency was assessed with components of the International Index of Erectile Function and phosphodiesterase type 5 inhibitor (PDE5) medication records. RESULTS: Sixty-two patients received ETS-IMRT, and 54 received s-IMRT; 1 patient did not receive radiation therapy. Before treatment, all patients reported erectile potency. No patients received androgen deprivation therapy. In the intention-to-treat analysis, treatment arms did not differ in potency preservation at 24 months (37.1% ETS-IMRT vs 31.5% s-IMRT, P = .53). Of 85 evaluable patients with International Index of Erectile Function and PDE5 medication follow-up, erectile potency was seen in 47.9% of patients in the ETS-IMRT arm and 46.0% of patients in the s-IMRT arm (P = .86). PDE5 inhibitors were initiated in 41.7% of ETS-IMRT patients and 35.1% of s-IMRT patients (P = .54). Among all patients enrolled, there was no difference in freedom from biochemical failure between those treated with ETS-IMRT and s-IMRT (5-year 91.8% vs 90.7%, respectively, P = .77), with a median follow-up of 7.4 years. There were no differences in acute or late gastrointestinal or genitourinary toxicity. An unplanned per-protocol analysis demonstrated no differences in potency preservation or secondary endpoints between patients who exceeded erectile tissue-sparing constraints and those who met constraints, although power was limited by attrition and unplanned dosimetric crossover. CONCLUSIONS: ETS-IMRT that strictly limits dose to the penile bulb and corporal bodies is safe and feasible. Use of this planning technique did not show an effect on potency preservation outcomes at 2 years, though power to detect a difference was limited.

Factors Associated with Reconstruction Failure and Major Complications After Postmastectomy Radiation to a Reconstructed Breast.

PURPOSE: Postmastectomy radiation therapy is known to increase risk of complications in the reconstruction setting. We aim to identify the variables associated with reconstruction failure and other major complications. METHODS AND MATERIALS: A prospectively collected institutional database was queried for patients with up to stage IIIC breast cancer treated from 2000 to 2017, undergoing mastectomy, immediate implant or autologous tissue reconstruction, and radiation to the reconstructed breast within 1 year of surgery. Reconstruction failure was defined as complication requiring surgical revision or implant removal. Additional major complications were defined as any infection, contracture, necrosis, or fibrosis. Covariates of interest included age, body mass index, smoking status, stage, hormone receptor and HER2 status, systemic therapy timing, radiation technique, nodal irradiation, and interval between surgery and start of postmastectomy radiation therapy. Differences in complication rates were assessed with χ² or Fisher exact tests. Competing risk regression was used to estimate hazard ratios; covariates were included one at a time to avoid over adjustment. RESULTS: A total of 206 reconstructed breasts in 202 patients resulted from our initial query, with 139 treated with intensity-modulated radiation therapy (IMRT) and 67 treated with conventional radiation therapy (CRT). Median follow-up was 45 months (range, 4-210 months); patient cohorts were generally similar. Eight patients were excluded from toxicity analysis for insufficient follow-up (<2 years). Overall, reconstruction failure and major complication rates were significantly lower in the IMRT group. Reconstruction failure rates were 3.0% for IMRT versus 16.4% for CRT (P = .002), and major complication rates were 6.8% for IMRT versus 24.6% for CRT (P < .001). On univariate analysis, CRT was significantly predictive of implant failure (hazard ratio, 5.54; P = .003) and increased complication rates (hazard ratio, 3.83; P = .001). Significance persisted on multivariable analysis. Survival outcomes were similar, with no difference in 2 year overall survival (P = .12) and local recurrence (P = .41). CONCLUSIONS: Using IMRT may improve reconstruction outcomes over CRT, with significantly lower reconstruction failure and complication rates without compromising local control or survival.

Lumbar Schwannoma as a Rare Cause of Radiculopathy in the Chiropractic Office: A Case Report.

Cauda equina tumors are rare, slow-growing, and typically benign. These tumors present with low back pain resembling disc displacement with radiculopathy and thus may go undiagnosed for months. A 52-year-old, otherwise healthy man presented to a chiropractor with a one-year history of worsening low back pain radiating to the right lower extremity, rated an 8/10 in severity and aggravated by recumbency. Previously, his primary care physician had ordered radiographs revealing mild lumbar degenerative changes, prescribed a non-steroidal anti-inflammatory medication, and referred him to an orthopedist and physical therapist. There had been no change in symptoms. Upon examination by the chiropractor, the patient had neurologic deficits, and due to progressive worsening, the chiropractor recommended magnetic resonance imaging (MRI), which the patient deferred due to cost. The chiropractor initiated a trial of care, with initial success; however, the patient's symptoms recurred, and he consented to an MRI. MRI revealed an intradural extramedullary lumbar tumor, and the chiropractor referred the patient to an oncologist, who referred the patient to a neurosurgeon. The neurosurgeon surgically removed the mass, with a biopsy confirming a schwannoma. The patient had significantly improved six weeks after surgery. This case highlights a patient with chronic low back pain for whom a chiropractor identified a cauda equina tumor and referred him for further evaluation and surgery. Clinicians should consider night pain and persistent symptoms, despite conservative care, as red flags warranting further investigation in those with low back pain. Providers should refer for neurosurgical evaluation when clinical and radiological findings suggest a cauda equina tumor.

Recommendations for the management of advanced and metastatic renal cell carcinoma: joint consensus statements from the Hong Kong Urological Association and the Hong Kong Society of Uro-Oncology.

INTRODUCTION: Kidney cancer, primarily renal cell carcinoma (RCC), ranks among the top 10 most common malignancies in the male population of Hong Kong. In 2019, members of two medical societies in Hong Kong formed an expert panel to establish a set of consensus statements for the management of metastatic RCC. On 22 June 2021, the same panel met to review recent evidence and reassess their positions regarding the management of advanced and metastatic RCC, with the aim of providing recommendations for physicians in Hong Kong. PARTICIPANTS: The panel included 12 experts (6 clinical oncologists and 6 urologists) who had extensive experience managing patients with RCC in Hong Kong. EVIDENCE: The panel reviewed randomised controlled trials, observational studies, systematic reviews/meta-analyses, and international clinical guidelines to address key clinical questions that were identified before the meeting. CONSENSUS PROCESS: In total, 15 key clinical questions were identified before the meeting, covering the surgical and systemic treatment of advanced or metastatic clear cell, sarcomatoid, and non-clear cell RCCs. At the meeting, the panellists voted on these questions, then discussed relevant evidence and practical considerations. CONCLUSIONS: The treatment landscape for advanced and metastatic RCC continues to evolve. More immune checkpoint inhibitor (ICI)-based combination regimens will be indicated for the treatment of metastatic clear cell RCC. There is increasing evidence concerning the benefit of adjuvant ICI treatment for resected advanced RCC. This article summarises recent evidence and expert insights regarding a series of key clinical questions about the management of advanced and metastatic RCC.

Polycomb contraction differentially regulates terminal human hematopoietic differentiation programs.

BACKGROUND: Lifelong production of the many types of mature blood cells from less differentiated progenitors is a hierarchically ordered process that spans multiple cell divisions. The nature and timing of the molecular events required to integrate the environmental signals, transcription factor activity, epigenetic modifications, and changes in gene expression involved are thus complex and still poorly understood. To address this gap, we generated comprehensive reference epigenomes of 8 phenotypically defined subsets of normal human cord blood. RESULTS: We describe a striking contraction of H3K27me3 density in differentiated myelo-erythroid cells that resembles a punctate pattern previously ascribed to pluripotent embryonic stem cells. Phenotypically distinct progenitor cell types display a nearly identical repressive H3K27me3 signature characterized by large organized chromatin K27-modification domains that are retained by mature lymphoid cells but lost in terminally differentiated monocytes and erythroblasts. We demonstrate that inhibition of polycomb group members predicted to control large organized chromatin K27-modification domains influences lymphoid and myeloid fate decisions of primary neonatal hematopoietic progenitors in vitro. We further show that a majority of active enhancers appear in early progenitors, a subset of which are DNA hypermethylated and become hypomethylated and induced during terminal differentiation. CONCLUSION: Primitive human hematopoietic cells display a unique repressive H3K27me3 signature that is retained by mature lymphoid cells but is lost in monocytes and erythroblasts. Intervention data implicate that control of this chromatin state change is a requisite part of the process whereby normal human hematopoietic progenitor cells make lymphoid and myeloid fate decisions.

Early Prostate-Specific Antigen Kinetics for Low- and Intermediate-Risk Prostate Cancer Treated With Definitive Radiation Therapy.

PURPOSE: This study used a patient-specific model to characterize and compare ideal prostate-specific antigen (PSA) kinetics for low- and intermediate-risk prostate cancer after definitive radiation treatment with conventionally fractionated, hypofractionated, stereotactic body radiation therapy, or brachytherapy, both high-dose and low-dose rate. METHODS AND MATERIALS: This retrospective analysis includes low- and intermediate-risk patients with prostate cancer treated between 1998 and 2018 at an National Cancer Institute-designated comprehensive cancer center. Demographics and treatment characteristics were prospectively collected. Patients had at least 2 PSA measurements within 24 months of treatment and were free from biochemical recurrence. The incidence of, time to, and risk factors for PSA nadir (nPSA) and bounce (bPSA) were analyzed at 24 months after radiation therapy. Ideal PSA kinetics were characterized for each modality and compared. RESULTS: Of 1042 patients, 45% had low-risk cancer, 37% favorable intermediate risk, and 19% unfavorable intermediate risk. nPSAs were higher for ablative modalities, both as absolute nPSA and relative to initial PSA. Median time to nPSA ranged from 14.8 to 17.1 months. Over 50% treated with nonablative therapy (conventionally fractionated, hypofractionated, and low-dose rate) reached an nPSA threshold of ≤0.5 ng/mL compared with 23% of stereotactic body radiation therapy and 33% of high-dose rate cohorts. The incidence of bPSA was 13.3% and not affected by treatment modality, Gleason score, or prostate volume. PSA decay rate was faster for ablative therapies in the 6- to 24-month period. CONCLUSIONS: Analysis of PSA within 24 months after radiation therapy revealed ablative therapies are associated with a latent PSA response and higher nPSA. Multivariable logistics modeling revealed younger age, initial PSA above the median, presence of bPSA, and ablative therapy as predictors for not achieving nPSA ≤0.5 ng/mL. PSA decay rate appears to be faster in ablative therapies after a latent period. Understanding the different PSA kinetic profiles is necessary to assess treatment response and survey for disease recurrence.

Neoadjuvant Chemoradiation Impacts the Prognostic Effect of Surgical Margin Status in Pancreatic Adenocarcinoma.

BACKGROUND: Many studies show significantly improved survival after R0 resection compared with R1 resection in pancreatic adenocarcinoma (PAC); however, the effect of neoadjuvant chemoradiation (NACRT) on this association is unknown. OBJECTIVE: The aim of this study was to evaluate the prognostic significance of positive surgical margins (SMs) after NACRT compared with upfront surgery + adjuvant therapy in PAC. METHODS: All cases of surgically resected PAC at a single institution were reviewed from 1996 to 2014; patients treated with palliative intent, metastatic disease, and biliary/ampullary tumors were excluded. The primary endpoint was overall survival (OS). RESULTS: Overall, 300 patients were included; 134 patients received NACRT with concurrent 5-fluorouracil or gemcitabine followed by surgery, and 166 patients received upfront surgery (+ adjuvant chemotherapy in 72% of patients and RT in 65%); 31% of both groups had a positive SM (+SM). The median OS for patients with a +SM or negative SM (-SM) was 26.6 and 31.6 months, respectively for NACRT, and 12.0 and 24.5 months, respectively, for upfront surgery. OS was significantly improved with -SM compared with +SM in both groups (p = 0.006). When resection yielded +SM, NACRT patients had improved OS compared with upfront surgery patients (p < 0.001). On multivariable analysis, +SM in the upfront surgery group (hazard ratio [HR] 2.94, 95% confidence interval [CI] 2.04-4.24; p < 0.001) and older age (HR 1.01, 95% CI 1.00-1.03, per year; p = 0.007) predicted worse OS. +SM in the NACRT group was not associated with worse OS (HR 1.09, 95% CI 0.72-1.65; p = 0.70). CONCLUSION: Patients with a positive margin after NACRT and surgery had longer survival compared with patients with a positive margin after upfront surgery. NACRT should be strongly considered for patients at high risk of R1 resections.

Acute kidney injury following hepatectomy and its impact on long-term survival for patients with hepatocellular carcinoma.

BACKGROUND: Acute kidney injury (AKI) is increasingly being recognized after hepatectomy. This study aimed to identify factors predicting its occurrence and its impact on long-term outcome among patients with hepatocellular carcinoma (HCC). METHODS: This was a retrospective analysis of the incidence of AKI, factors predicting its occurrence, and its impact on patients undergoing hepatectomy between September 2007 and December 2018. A subgroup analysis included patients with histologically proven HCC. RESULTS: The incidence of AKI was 9.2 per cent in 930 patients. AKI was associated with increased mortality, morbidity, posthepatectomy liver failure (PHLF), and a longer hospital stay. On multivariable analysis, study period December 2013 to December 2018, diabetes mellitus, mean intraoperative BP below 72.1 mmHg, operative blood loss exceeding 377ml, high Model for End-Stage Liver Disease (MELD) score, and PHLF were predictive factors for AKI. Among 560 patients with HCC, hypertension, BP below 76.9 mmHg, blood loss greater than 378ml, MELD score, and PHLF were predictive factors. The 1-, 3-, and 5-year overall survival rates were 74.1, 59.2, and 51.6 per cent respectively for patients with AKI, and 91.8, 77.9, and 67.3 per cent for those without AKI. Corresponding 1-, 3-, and 5-year disease-free survival rates were 56.9, 42.3, and 35.4 per cent respectively in the AKI group, and 71.7, 54.5, and 46.2 per cent in the no-AKI group. AKI was an independent predictor of survival in multivariable analysis. CONCLUSION: AKI is associated with longer hospital stay, and higher morbidity and mortality rates. It is also associated with shorter long-term survival among patients with HCC. To avoid AKI, control of blood loss and maintaining a reasonable BP (72-77 mmHg) during hepatectomy is important.

Kidney biopsy practice amongst Australasian nephrologists.

BACKGROUND: Percutaneous kidney biopsy is the gold standard investigation for the diagnosis of kidney diseases. The associated risks of the procedure depend on the skill and experience of the proceduralist as well as the characteristics of the patient. The Kidney Health Australia - Caring for Australasians with Renal Impairment (KHA-CARI) guidelines on kidney biopsies, published in 2019, are the only published national kidney biopsy guidelines. As such, this study surveys current kidney biopsy practices in Australasia and examines how they align with the Australian guidelines, as well as international biopsy practice. METHODS: A cross-sectional, multiple-choice questionnaire was developed examining precautions prior to kidney biopsy; rationalisation of medications prior to kidney biopsy; technical aspects of kidney biopsy; complications of kidney biopsy; and indications for kidney biopsy. This was distributed to all members of the Australian and New Zealand Society of Nephrology (ANZSN). RESULTS: The response rate for this survey is approximately 21.4 % (182/850). Respondents found agreement (> 75.0 %) in only six out of the twelve questions (50.0 %) which assessed their practice against the KHA-CARI guidelines. CONCLUSIONS: This is the first study of its kind where kidney biopsy practices are examined against a clinical guideline. Furthermore, responses showed that practices were incongruent with guidelines and that there was a lack of consensus on many issues.

Normothermic ex vivo perfusion of the limb allograft depletes donor leukocytes prior to transplantation.

INTRODUCTION: The donor immune compartment plays a central role in graft rejection of the vascularised composite allograft (VCA) by contributing to 'direct presentation'. Using our limb ex vivo normothermic machine perfusion (EVNP) protocol designed for prolonged allograft preservation, this study aimed to assess whether donor leukocytes responsible for allograft rejection are mobilised from the donor compartment. METHODS: Five genetically different pig forelimbs underwent perfusion via the brachial and radial collateral artery for 6 h after 2 h of cold storage. Oxygenated haemodilute leucocyte-deplete blood was recirculated at normothermia using an extracorporeal perfusion system. Tissue perfusion was evaluated clinically and biochemically via blood perfusate. The temporal kinetics of donor leucocyte extravasation, cytokine secretion and cell-free DNA was characterised in the circulating perfusate. RESULTS: Flow cytometry revealed increasing populations of viable leukocytes over time, reaching 49 billion leukocytes by 6 h. T (3.0 × 109 cells) and B cells (3.1 × 108 cells) lymphocytes, monocytes (2.7 × 109 cells), granulocytes (8.1 × 109 cells), NK (6.3 × 108) and γδ (8.1 × 108) cells were all identified. Regulatory T cells comprised a minor population (1.6 × 107 cells). There was a cumulative increase in pro-inflammatory cytokines suggesting that the donor limb has the capacity to elicit significant inflammatory responses that could contribute to leucocyte activation and diapedesis. CONCLUSION: EVNP not only acts as a preservation tool, but could also be utilized to immunodeplete the VCA allograft prior to transplantation. This has clinical implications to mitigate acute rejection and prevent graft dysfunction and supports the future application of machine perfusion in graft preservation and immune modulation.

Randomized preclinical study of machine perfusion in vascularized composite allografts.

BACKGROUND: Attempts to improve limb preservation for transplantation using ex vivo perfusion have yielded promising results. However, metabolic acidosis, aberrant perfusate biochemistry and significant perfusion-induced oedema are reported universally. Optimizing perfusion protocols is therefore essential for maintaining tissue health. METHODS: A randomized, two-stage open preclinical trial design was used to determine the optimal temperature and mean arterial pressure for machine perfusion. Conditions compared were: normothermic machine perfusion at 70 mmHg (NMP-70); subnormothermic perfusion (28°C) at 70 mmHg; subnormothermic (28°C) perfusion at 50 mmHg; and hypothermic perfusion (10°C) at 30 mmHg. Following this, a head-to-head experiment was undertaken comparing the optimal machine perfusion with static cold storage. Paired bilateral limbs (10 in total) were randomized to either 8 h of static cold storage, or 2 h of static cold storage and 6 h of optimal machine perfusion. Both groups of limbs were then reperfused on a circuit primed with matched blood from unrelated donors for 4 h without immunosuppression. RESULTS: NMP-70 resulted in less tissue injury and stable perfusion biochemistry. Assessing reperfusion outcomes, static cold storage resulted in acidosis with increased lactate and a worsening electrolyte profile, necessitating bolus infusions of bicarbonate to prevent graft loss. Conversely, NMP-70 was associated with haemodynamic and biochemical stability. Histologically, on reperfusion with allogeneic whole blood, limbs subjected to static cold storage exhibited multifocal ischaemic injury and increased inflammation, which was absent with NMP-70. Static cold storage also resulted in significant oedema compared with NMP-70. CONCLUSION: Normothermic perfusion resulted in superior graft preservation and less reperfusion injury compared with the current static cold storage protocol.

A Pooled Toxicity Analysis of Moderately Hypofractionated Proton Beam Therapy and Intensity Modulated Radiation Therapy in Early-Stage Prostate Cancer Patients.

PURPOSE: Data comparing moderately hypofractionated intensity modulated radiation therapy (IMRT) and proton beam therapy (PBT) are lacking. We aim to compare late toxicity profiles of patients with early-stage prostate cancer treated with moderately hypofractionated PBT and IMRT. METHODS AND MATERIALS: This multi-institutional analysis included patients with low- or intermediate-risk biopsy-proven prostate adenocarcinoma from 7 tertiary referral centers treated from 1998 to 2018. All patients were treated with moderately hypofractionated radiation, defined as 250 to 300 cGy per daily fraction given for 4 to 6 weeks, and stratified by use of IMRT or PBT. Primary outcomes were late genitourinary (GU) and gastrointestinal (GI) toxicity. Adjusted toxicity rates were calculated using inverse probability of treatment weighting, accounting for race, National Comprehensive Cancer Network risk group, age, pretreatment International Prostate Symptom Score (GU only), and anticoagulant use (GI only). RESULTS: A total of 1850 patients were included: 1282 IMRT (median follow-up 80.0 months) and 568 PBT (median follow-up 43.9 months). Overall toxicity rates were low, with the majority of patients experiencing no late GU (56.6%, n = 1048) or late GI (74.4%, n = 1377) toxicity. No difference was seen in the rates of late toxicity between the groups, with late grade 3+ GU toxicity of 2.0% versus 3.9% (odds ratio [OR] 0.47; 95% confidence interval 0.17-1.28) and late grade 2+ GI toxicity of 14.6% versus 4.7% (OR 2.69; confidence interval 0.80-9.05) for the PBT and IMRT cohorts, respectively. On multivariable analysis, no factors were significantly predictive of GU toxicity, and only anticoagulant use was significantly predictive of GI toxicity (OR 1.90; P = .008). CONCLUSIONS: In this large, multi-institutional analysis of 1850 patients with early-stage prostate cancer, treatment with moderately hypofractionated IMRT and PBT resulted in low rates of toxicity. No difference was seen in late GI and GU toxicity between the modalities during long-term follow-up. Both treatments are safe and well tolerated.