Efficacy and toxicity of primary re-irradiation for malignant spinal cord compression based on radiobiological modelling: a phase II clinical trial.

BACKGROUND: The efficacy and safety of primary re-irradiation for MSCC are not known. Our aim was to establish the efficacy and safety of biologically effective dose-based re-irradiation. METHODS: Patients presenting with MSCC at a previously irradiated spine segment, and not proceeding with surgical decompression, were eligible. A 3 Gray per fraction experimental schedule (minimum 18 Gy/6 fractions, maximum 30 Gy/10 fractions) was used, delivering a maximum cumulative spinal dose of 100 Gy2 if the interval since the last radiotherapy was within 6 months, or 130 Gy2 if longer. The primary outcome was a change in mobility from week 1 to week 5 post-treatment, as assessed by the Tomita score. The RTOG SOMA score was used to screen for spinal toxicity, and an MRI performed to assess for radiation-induced myelopathy (RIM). RESULTS: Twenty-two patients were enroled, of whom eleven were evaluable for the primary outcome. Nine of eleven (81.8%) had stable or improved Tomita scores at 5 weeks. One of eight (12.5%) evaluable for late toxicity developed RIM. CONCLUSIONS: Re-irradiation is an efficacious treatment for MSCC. There is a risk of RIM with a cumulative dose of 120 Gy2. CLINICAL TRIAL REGISTRATION: Cancer Trials Ireland (ICORG 07-11); NCT00974168.

Androgen deprivation therapy use and duration with definitive radiotherapy for localised prostate cancer: an individual patient data meta-analysis.

BACKGROUND: Randomised trials have investigated various androgen deprivation therapy (ADT) intensification strategies in men receiving radiotherapy for the treatment of prostate cancer. This individual patient data meta-analysis of relevant randomised trials aimed to quantify the benefit of these interventions in aggregate and in clinically relevant subgroups. METHODS: For this meta-analysis, we performed a systematic literature search in MEDLINE, Embase, trial registries, the Web of Science, Scopus, and conference proceedings to identify trials with results published in English between Jan 1, 1962, and Dec 30, 2020. Multicentre randomised trials were eligible if they evaluated the use or prolongation of ADT (or both) in men with localised prostate cancer receiving definitive radiotherapy, reported or collected distant metastasis and survival data, and used ADT for a protocol-defined finite duration. The Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) Consortium was accessed to obtain individual patient data from randomised trials. The primary outcome was metastasis-free survival. Hazard ratios (HRs) were obtained through stratified Cox models for ADT use (radiotherapy alone vs radiotherapy plus ADT), neoadjuvant ADT extension (ie, extension of total ADT duration in the neoadjuvant setting from 3-4 months to 6-9 months), and adjuvant ADT prolongation (ie, prolongation of total ADT duration in the adjuvant setting from 4-6 months to 18-36 months). Formal interaction tests between interventions and metastasis-free survival were done for prespecified subgroups defined by age, National Comprehensive Cancer Network (NCCN) risk group, and radiotherapy dose. This meta-analysis is registered with PROSPERO, CRD42021236855. FINDINGS: Our search returned 12 eligible trials that provided individual patient data (10 853 patients) with a median follow-up of 11·4 years (IQR 9·0-15·0). The addition of ADT to radiotherapy significantly improved metastasis-free survival (HR 0·83 [95% CI 0·77-0·89], p<0·0001), as did adjuvant ADT prolongation (0·84 [0·78-0·91], p<0·0001), but neoadjuvant ADT extension did not (0·95 [0·83-1·09], p=0·50). Treatment effects were similar irrespective of radiotherapy dose, patient age, or NCCN risk group. INTERPRETATION: Our findings provide the strongest level of evidence so far to the magnitude of the benefit of ADT treatment intensification with radiotherapy for men with localised prostate cancer. Adding ADT and prolonging the portion of ADT that follows radiotherapy is associated with improved metastasis-free survival in men, regardless of risk group, age, and radiotherapy dose delivered; however, the magnitude of the benefit could vary and shared decision making with patients is recommended. FUNDING: University Hospitals Seidman Cancer Center, Prostate Cancer Foundation, and the American Society for Radiation Oncology.

Non-inferiority randomised phase 3 trial comparing two radiation schedules (single vs. five fractions) in malignant spinal cord compression.

BACKGROUND: The optimal EBRT schedule for MSCC is undetermined. Our aim was to determine whether a single fraction (SF) was non-inferior to five daily fractions (5Fx), for functional motor outcome. METHODS: Patients not proceeding with surgical decompression in this multicentre non-inferiority, Phase 3 trial were randomised to 10 Gy/SF or 20 Gy/5Fx. A change in mobility from baseline to 5 weeks for each patient, was evaluated by a Modified Tomita score: 1 = 'Walk unaided', 2 = 'With walking aid' and 3 = 'Bed-bound'. The margin used to establish non-inferiority was a detrimental change of -0.4 in the mean difference between arms. RESULTS: One-hundred and twelve eligible patients were enrolled. Seventy-three patients aged 30-87 were evaluated for the primary analysis. The 95% CI for the difference in the mean change in mobility scores between arms was -0.12 to 0.6. Since -0.4 is not included in the interval, there is evidence that 10 Gy/SF is non-inferior to 20 Gy/5Fx. One grade 3 AE was reported in the 5Fx arm. Twelve (26%) patients in the 5Fx arm had a Grade 2-3 AE compared with six (11%) patients in the SF arm (p = 0.093). CONCLUSION: For mobility preservation, one 10-Gy fraction is non-inferior to 20 Gy in five fractions, in patients with MSCC not proceeding with surgical decompression. CLINICAL TRIAL REGISTRATION: Cancer Trials Ireland ICORG 05-03; NCT00968643; EU-20952.

Temporal patterns of late bowel and bladder radiotherapy toxicity in a randomised controlled trial assessing duration of neo-adjuvant hormones in prostate cancer.

BACKGROUND: To assess the temporal patterns of late gastrointestinal (GI) and genitourinary (GU) radiotherapy toxicity and resolution rates in a randomised controlled trial (All-Ireland Cooperative Oncology Research Group 97-01) assessing duration of neo-adjuvant (NA) hormone therapy for localised prostate cancer. MATERIAL AND METHODS: Node negative patients with > 1 of: PSA > 20 ng/mL, Gleason score ≥ 7, and stage T3 or more, were included. Follow-up, including toxicity assessment, was three-monthly in the early stages and yearly thereafter. RESULTS: Median follow-up from the end of RT was 6.8 years. In the interval between 90 days following the end of RT and the last toxicity assessment, GI and GU toxicity (any grade) was found in 50% and 51% of 240 and 241 patients, respectively. For those who did develop toxicity, the median time from end of RT until the first development of any grade GI or GU toxicity was 1.2 years and 1.6 years, respectively, whilst median time to final resolution was 1.6 years and 2.2 years, respectively. Grade 2 (G2) or greater GI and GU toxicity occurred in 29 (12.1%) and 40 (16.6%) patients, respectively. The proportion with unresolved G2 + GI and GU toxicity was 89% and 79%, respectively, in year 1, 69% and 65% in year 2, 59% and 52% in year 3 and 27% and 32% in year 5. CONCLUSION: Long-term toxicities continue to occur many years after NA hormone therapy and RT. The rate of occurrence does not appear to reduce within the time frame during which our patients were followed. The percentage of patients suffering from G2 + toxicity at any time is however low. Resolution of these toxicities continues for the duration of the follow-up.

Prognostic Impact of Prostate-Specific Antigen at 6 Months After Radiotherapy in Localized Prostate Cancer: An Individual Patient Data Analysis of Randomized Trials.

PURPOSE: We sought to evaluate the prognostic impact of prostate-specific antigen (PSA) at 6 months after completion of radiotherapy (RT) in patients treated with RT alone, RT plus short-term (st; 3-6 months), and RT plus long-term (lt; 24-36 months) androgen-deprivation therapy (ADT). PATIENTS AND METHODS: Individual patient data were obtained from 16 randomized trials evaluating RT ± ADT for localized prostate cancer (PCa) between 1987 and 2011. The lowest PSA recorded within 6 months after RT completion was identified and categorized as < or ≥0.1 ng/mL. The primary outcomes were metastasis-free survival (MFS), PCa-specific mortality (PCSM), and overall survival (OS), from 12 months after random assignment. RESULTS: Ninety-eight percent (n = 2,339/2,376) of patients allocated to RT alone, 84% (n = 4,756/5,658) allocated to RT + stADT, and 77% (n = 1,258/1,626) allocated to RT + ltADT had PSA ≥0.1 ng/mL within 6 months after completing RT. PSA ≥0.1 ng/mL was associated with lower MFS and OS and higher PCSM among patients allocated to RT ± ADT (RT - MFS: hazard ratio [HR], 2.24 [95% CI, 1.21 to 4.16]; PCSM: subdistribution hazard ratio [sHR], 1.82 [0.51 to 6.49]; OS: HR, 1.72 [0.97 to 3.05]; RT + stADT - MFS: HR, 1.27 [1.12 to 1.44]; PCSM: sHR, 2.10 [1.52 to 2.92]; OS: HR, 1.26 [1.11 to 1.44]; RT + ltADT - MFS: HR, 1.58 [1.27 to 1.96]; PCSM: sHR, 1.97 [1.11 to 3.49]; OS: HR, 1.59 [1.27 to 1.99]). Five-year MFS rates among patients allocated to RT, RT + stADT, and RT + ltADT were 91% versus 79%, 83% versus 76%, and 87% versus 74%, respectively, based on PSA < or ≥0.1 ng/mL. CONCLUSION: PSA ≥0.1 ng/mL within 6 months after RT completion was prognostic for lt outcomes in patients treated with RT ± ADT for localized PCa. This can be used to counsel patients treated with RT ± ADT and in guiding clinical trial design evaluating novel systemic therapies with RT + ADT as well as (de)intensification strategies.

Interobserver Variability of Gross Tumor Volume Delineation for Colorectal Liver Metastases Using Computed Tomography and Magnetic Resonance Imaging.

Purpose: The purpose of this study was to evaluate the interobserver variability in the contouring of the gross tumor volume (GTV) on magnetic resonance (MR) imaging and computed tomography (CT) for colorectal liver metastases in the setting of SABR. Methods and Materials: Three expert radiation oncologists contoured 10 GTV volumes on 3 MR imaging sequences and on the CT image data set. Three metrics were chosen to evaluate the interobserver variability: the conformity index, the DICE coefficient, and the maximum Hausdorff distance (HDmax). Statistical analysis of the results was performed using a 1-sided permutation test. Results: For all 3 metrics, the MR liver acquisition volume acquisition (MR LAVA) showed the lowest interobserver variability. Analysis showed a significant difference (P < .01) in the mean DICE, an overlap metric, for MR LAVA (0.82) and CT (0.74). The HDmax that highlights boundary errors also showed a significant difference (P = .04) with MR LAVA having a lower mean HDmax (7.2 mm) compared with CT (5.7 mm). The mean HDmax for both MR single shot fast spin echo (SSFSE) (19.3 mm) and diffusion weighted image (9.5 mm) showed large interobserver variability with MR SSFSE having a mean HDmax of 19.3 mm. A volume comparison between MR LAVA and CT showed a significantly higher volume for small GTVs (<5 cm3) when using MR LAVA for contouring in comparison to CT. Conclusions: This study reported the lowest interobserver variability for the MR LAVA, thus indicating the benefit of using MR to complement CT when contouring GTV for colorectal liver metastases.

The effect of anaemia on normal tissue toxicity and survival outcomes in prostate cancer treated with radical radiotherapy and neo-adjuvant androgen deprivation.

OBJECTIVE: It has been established that survival and toxicity outcomes in some cancer types could be influenced by haemoglobin (Hb) levels. This study aims to determine if pre-treatment Hb is associated with late toxicity or survival outcomes in prostate cancer. METHODS: Data from one Phase III randomised controlled trial and one single arm translational trial were analysed. Patients had localized prostate cancer and received ≥70 Gy radiotherapy and neo-adjuvant androgen deprivation between 1997 and 2013. RESULTS: 302 males were included. Median follow-up was 6.8 years for toxicity and 10.3 years for survival outcomes. Patients with Hb below the reference range were more likely to experience Grade 2-3 late gastrointestinal toxicity than patients with Hb within the range (p = 0.050). Neither late genitourinary toxicity, erectile function toxicity, prostate-specific antigen relapse free survival nor overall survival of patients were statistically significantly different between groups. CONCLUSION: Anaemia in prostate cancer is found in the minority of patients and is usually mild. Prostate cancer patients undergoing radiotherapy with low Hb were more likely to experience Grade 2-3 late gastrointestinal toxicity. ADVANCES IN KNOWLEDGE: This study is one of the first in the published literature to investigate the role of Hb in prostate cancer toxicity and survival. We have found an association between Hb below the reference range and late GI toxicity. Consideration should be given to further investigating patients with iron deficiency anaemia to guide management options and outrule underlying GI pathology before proceeding with radiotherapy treatment.

The etiology of community-acquired pneumonia in Australia: why penicillin plus doxycycline or a macrolide is the most appropriate therapy.

BACKGROUND: Available data on the etiology of community-acquired pneumonia (CAP) in Australia are very limited. Local treatment guidelines promote the use of combination therapy with agents such as penicillin or amoxycillin combined with either doxycycline or a macrolide. METHODS: The Australian CAP Study (ACAPS) was a prospective, multicenter study of 885 episodes of CAP in which all patients underwent detailed assessment for bacterial and viral pathogens (cultures, urinary antigen testing, serological methods, and polymerase chain reaction). Antibiotic agents and relevant clinical outcomes were recorded. RESULTS: The etiology was identified in 404 (45.6%) of 885 episodes, with the most frequent causes being Streptococcus pneumoniae (14%), Mycoplasma pneumoniae (9%), and respiratory viruses (15%; influenza, picornavirus, respiratory syncytial virus, parainfluenza virus, and adenovirus). Antibiotic-resistant pathogens were rare: only 5.4% of patients had an infection for which therapy with penicillin plus doxycycline would potentially fail. Concordance with local antibiotic recommendations was high (82.4%), with the most commonly prescribed regimens being a penicillin plus either doxycycline or a macrolide (55.8%) or ceftriaxone plus either doxycycline or a macrolide (36.8%). The 30-day mortality rate was 5.6% (50 of 885 episodes), and mechanical ventilation or vasopressor support were required in 94 episodes (10.6%). Outcomes were not compromised by receipt of narrower-spectrum beta-lactams, and they did not differ on the basis of whether a pathogen was identified. CONCLUSIONS: The vast majority of patients with CAP can be treated successfully with narrow-spectrum beta-lactam treatment, such as penicillin combined with doxycycline or a macrolide. Greater use of such therapy could potentially reduce the emergence of antibiotic resistance among common bacterial pathogens.

SMART-COP: a tool for predicting the need for intensive respiratory or vasopressor support in community-acquired pneumonia.

BACKGROUND: Existing severity assessment tools, such as the pneumonia severity index (PSI) and CURB-65 (tool based on confusion, urea level, respiratory rate, blood pressure, and age >or=65 years), predict 30-day mortality in community-acquired pneumonia (CAP) and have limited ability to predict which patients will require intensive respiratory or vasopressor support (IRVS). METHODS: The Australian CAP Study (ACAPS) was a prospective study of 882 episodes in which each patient had a detailed assessment of severity features, etiology, and treatment outcomes. Multivariate logistic regression was performed to identify features at initial assessment that were associated with receipt of IRVS. These results were converted into a simple points-based severity tool that was validated in 5 external databases, totaling 7464 patients. RESULTS: In ACAPS, 10.3% of patients received IRVS, and the 30-day mortality rate was 5.7%. The features statistically significantly associated with receipt of IRVS were low systolic blood pressure (2 points), multilobar chest radiography involvement (1 point), low albumin level (1 point), high respiratory rate (1 point), tachycardia (1 point), confusion (1 point), poor oxygenation (2 points), and low arterial pH (2 points): SMART-COP. A SMART-COP score of >or=3 points identified 92% of patients who received IRVS, including 84% of patients who did not need immediate admission to the intensive care unit. Accuracy was also high in the 5 validation databases. Sensitivities of PSI and CURB-65 for identifying the need for IRVS were 74% and 39%, respectively. CONCLUSIONS: SMART-COP is a simple, practical clinical tool for accurately predicting the need for IRVS that is likely to assist clinicians in determining CAP severity.

Proenkephalin expression and enkephalin release are widely observed in non-neuronal tissues.

Enkephalins are opioid peptides that are found at high levels in the brain and endocrine tissues. Studies have shown that enkephalins play an important role in behavior, pain, cardiac function, cellular growth, immunity, and ischemic tolerance. Our global hypothesis is that enkephalins are released from non-neuronal tissues in response to brief ischemia or exercise, and that this release contributes to cardioprotection. To identify tissues that could serve as potential sources of enkephalins, we used real-time PCR, Western blot analysis, ELISA, immunofluorescence microscopy, and ex vivo models of enkephalin release. We found widespread expression of preproenkephalin (pPENK) mRNA and production of the enkephalin precursor protein proenkephalin (PENK) in rat and mouse tissues, as well as in tissues and cells from humans and pigs. Immunofluorescence microscopy with anti-enkephalin antisera demonstrated immunoreactivity in rat tissues, including heart and skeletal muscle myocytes, intestinal and kidney epithelium, and intestinal smooth muscle cells. Finally, isolated tissue studies showed that heart, skeletal muscle, and intestine released enkephalins ex vivo. Together our studies indicate that multiple non-neuronal tissues produce PENK and release enkephalins. These data support the hypothesis that non-neuronal tissues could play a role in both local and systemic enkephalin-mediated effects.

Abnormal hCG levels in a patient with treated stage I seminoma: a diagnostic dilemma.

BACKGROUND: We report the case of a patient with treated Stage Ia seminoma who was found to have an elevated beta human chorionic gonadotrophin (hCG) on routine follow - up. This instigated restaging and could have lead to commencement of chemotherapy. CASE PRESENTATION: The patient was a bodybuilder, and following a negative metastatic work - up, admitted to injecting exogenous beta hCG. This was done to reduce withdrawal symptoms from androgen abuse. The patient remains well eight years post diagnosis. CONCLUSION: This case highlights the need for surgical oncologists to conduct vigilant screening of young male patients with a history of testicular germ cell tumours and who may indulge in steroid abuse.

A comparison of bladder volumes based on treatment planning CT and BladderScan® BVI 6100 ultrasound device in a prostate radiation therapy population.

OBJECTIVE:: The aim of this study is to investigate if a handheld ultrasound device (BladderScan® BVI 6100) can accurately measure bladder volumes in prostate radiotherapy (RT) patients. METHODS:: A comparison was made of contoured bladder volumes based on treatment planning CT (TPCT) and BladderScan® BVI 6100 ultrasound device in a large prostate RT population. Three bladder volume (BV) measurements were taken using the bladder volume instrument (BVI) device on prostate RT patients immediately prior to TPCT (n = 190). The CT delineation bladder volumes were also recorded. The mean of the three BVI readings (BVImean) and the maximum (BVImax) of the readings were considered for a comparative analysis. RESULTS:: There was a strong positive correlation between the BVI and CT delineated bladder volumes (BVImean r = 0.825; BVImax r = 0.830). The mean difference [± standard deviation (SD)] was an underestimation of BV for both BVImean and BVImax (44.8 ± 88.2 ml and 32.9 ± 87.5 ml, respectively). CONCLUSION:: This is the largest study to date (n = 190), assessing the accuracy of the BladderScan® BVI 6100 in the prostate RT population. The BVI 6100 provides an acceptable indication of BV for use in prostate RT patients for the purposes of monitoring BV. ADVANCES IN KNOWLEDGE:: The BladderScan® BVI 6100 provides a convenient and non-irradiating method of indicating BV for use in prostate RT patients.

Prospective Study of Central versus Peripheral Obesity in Total Knee Arthroplasty.

PURPOSE: Body mass index (BMI) is often used to predict surgical difficulty in patients receiving total knee arthroplasty (TKA); however, BMI neglects variation in the central versus peripheral distribution of adipose tissue. We sought to examine whether anthropometric factors, rather than BMI alone, may serve as a more effective indication of surgical difficulty in TKA. MATERIALS AND METHODS: We prospectively enrolled 67 patients undergoing primary TKA. Correlation coefficients were used to evaluate the associations of tourniquet time, a surrogate of surgical difficulty, with BMI, pre- and intraoperative anthropometric measurements, and radiographic knee alignment. Similarly, Knee Injury and Osteoarthritis Outcome Score (KOOS) was compared to BMI. RESULTS: Tourniquet time was significantly associated with preoperative inferior knee circumference (p=0.025) and ankle circumference (p=0.003) as well as the intraoperative depth of incision at the quadriceps (p=0.014). BMI was not significantly associated with tourniquet time or any of the radiographic parameters or KOOS scores. CONCLUSIONS: Inferior knee circumference, ankle circumference, and depth of incision at the quadriceps (measures of peripheral obesity) are likely better predictors of surgical difficulty than BMI. Further study of alternative surgical indicators should investigate patients that may be deterred from TKA for high BMI, despite relatively low peripheral obesity.

The potential for increased tumor control probability in non-small cell lung cancer with a hypofractionated integrated boost to the gross tumor volume.

Treatment outcomes in locally advanced non-small cell lung cancer (NSCLC) to date have been poor, with normal tissue toxicity often limiting the dose that can be delivered to the tumor. Treatment intensification in NSCLC via targeted dose escalation with modern delivery techniques may offer the potential for a significant increase in tumor control probability (TCP) without a clinically significant increase in organ-at-risk (OAR) toxicity. In this planning study, 20 patients were re-planned with a volumetric modulated arc therapy (VMAT) and an inhomogeneous dose distribution with iteratively escalated doses to the gross tumor volume (iGTV) (composite GTV across multiple 4-dimensional computed tomography [4DCT] phases) in a series of 20 fraction regimes. For each plan OAR doses, target coverage and predicted TCPs were collected and compared with homogenous 3-dimensional (3D) and VMAT plans, as well as with each other. In 70% of patients, it was possible to escalate to 75 Gy in 20 fractions within OAR tolerances, opening the possibility of treating these patients to a biological effective dose (BED) of 103.1 Gy10. This planning study forms the basis of a clinical trial INTENSE (Inhomogeneous Targeted Dose Escalation in Non-Small CEll Lung Cancer), CTRIAL 15-47.

Cancer Trials Ireland (ICORG) 06-34: A multi-centre clinical trial using three-dimensional conformal radiation therapy to reduce the toxicity of palliative radiation for lung cancer.

TITLE: Cancer Trials Ireland (ICORG) 06-34: A multi-centre clinical trial using three-dimensional conformal radiation therapy to reduce the toxicity of palliative radiation for lung cancer. NCT01176487. BACKGROUND & PURPOSE: Trials of radiation therapy for the palliation of intra-thoracic symptoms from locally advanced non-small cell lung cancer (NSCLC) have concentrated on optimising fractionation and dose schedules. In these trials, the rates of oesophagitis induced by this "palliative" therapy have been unacceptably high. In contrast, this non-randomised, single-arm trial was designed to assess if more technically advanced treatment techniques would result in equivalent symptom relief and reduce the side-effect of symptomatic oesophagitis. MATERIALS & METHODS: Thirty-five evaluable patients with symptomatic locally advanced or metastatic NSCLC were treated using a three-dimensional conformal technique (3-DCRT) and standardised dose regimens of 39 Gy in 13 fractions, 20 Gy in 5 fractions or 17 Gy in 2 fractions. Treatment plans sought to minimise oesophageal dose. Oesophagitis was recorded during treatment, at two weeks, one month and three months following radiation therapy and 3-6 monthly thereafter. Mean dose to the irradiated oesophagus was calculated for all treatment plans. RESULTS: Five patients (14%) had experienced grade 2 oesophagitis or dysphagia or both during treatment and 2 other patients had these side effects at the 2-week follow-up. At follow-up of one month after therapy, there was no grade two or higher oesophagitis or dysphagia reported. 22 patients were eligible for assessment of late toxicity. Five of these patients reported oesophagitis or dysphagia (one had grade 3 dysphagia, two had grade 2 oesophagitis, one of whom also had grade 2 dysphagia). Quality of Life (QoL) data at baseline and at 1-month follow up were available for 20 patients. At 1-month post radiation therapy, these patients had slightly less trouble taking a short walk, less shortness of breath, did not feel as weak, had better appetite and generally had a better overall quality of life than they did at baseline. They did report being slightly more tired. CONCLUSIONS: This trial is the first of its kind showing that 3-DCRT provides patients with lower rates of oesophageal toxicity whilst yielding acceptable rates of symptom control. (Sponsored by Cancer Trials Ireland (ICORG) Study number 06-34, the Friends of St. Luke's and the St. Luke's Institute of Cancer Research.).

Gastroesophageal reflux disease, acid suppression, and Mycobacterium avium complex pulmonary disease.

BACKGROUND: Weekly symptoms of gastroesophageal reflux disease (GERD) occur in 20% of the population, and GERD has been implicated in the pathophysiology of many respiratory diseases. Microaspiration of contaminated water is a potential portal of entry for Mycobacterium avium complex (MAC) organisms into the respiratory tract, and acid-suppression therapy may enhance the survival of mycobacteria in the stomach. This study aimed to assess the prevalence of GERD, swallowing disorders, reflux symptoms, and acid-suppression therapy in patients with MAC lung disease (MAC positive [MAC+]), and to compare these patients to control subjects without MAC lung disease (MAC negative [MAC-]). METHODS: Clinical information was collected on 58 MAC+ patients and 58 age- and sex-matched MAC- patients who were asked to complete a DeMeester questionnaire of reflux symptoms and to identify any acid-suppressive medication consumed. RESULTS: A clinical diagnosis of GERD was documented in 23 of 52 MAC+ patients (44.2%), compared to 16 MAC- patients (27.6%) [p = 0.019]. MAC+ patients consumed significantly more histamine type 2 receptor antagonists and prokinetic agents, and MAC- patients consumed more antacids. The mean DeMeester questionnaire score (+/- SD) for MAC+ patients was 1.39 +/- 1.8, and for MAC- patients was 0.88 +/- 1.4. (p = 0.098). Aspiration was suspected in nine MAC+ patients (15.5%), compared to three MAC- patients (5.2%) [p = 0.032]. There was no association between GERD and radiologic presentation of MAC disease. Consolidation and nodules > 5 mm were more common in those receiving acid suppression than those who were not. CONCLUSIONS: GERD, acid suppression, and clinically suspected aspiration are more common in patients with MAC lung disease than in similar patients without MAC disease.

Right Colectomy and Abdominal Perineal Resection for Cancer: Do Urinary Tract Infections Impact Outcomes?

BACKGROUND: We aim to assess the patient factors and concomitant infectious outcomes associated with urinary tract infection (UTI) occurrence and the impact of UTI on length of stay (LOS), re-admission, and death in a colorectal surgical population. PATIENTS AND METHODS: National Surgical Quality Improvement Program User Data for right colectomy and abdominal perineal resection (APR) procedures for cancer between 2006 and 2012 were analyzed. Concomitant infectious complications and timing of UTI diagnosis, inpatient versus outpatient, were considered. RESULTS: We identified 7,615 right colectomies with 107 (1.4%) UTIs and 2,493 APRs with 88 (3.5%) UTIs (p < 0.001). On multivariable analysis and correction for other post-operative complications, UTI remained statistically correlated with prolonged LOS for right colectomy and APR (LOS increases of 59.0% and 37.4%, respectively, p < 0.001) but not death. Patients with a diagnosis of UTI after discharge showed significantly increased re-admission rates compared with UTI diagnosis before discharge (37.7% vs. 9.7%, p < 0.001). CONCLUSIONS: After excluding deaths, outpatient UTI occurrences, and correcting for other infectious complications, UTI is associated with increased LOS but is not correlated with re-admission or death. Outpatient occurrence of UTI after hospital discharge is associated with a dramatic re-admission rate of 37.7%.

Robotic proctectomy for rectal cancer: analysis of 71 patients from a single institution.

BACKGROUND: Despite increasing use of robotic surgery for rectal cancer, few series have been published from the practice of generalizable US surgeons. METHODS: A retrospective chart review was performed for 71 consecutive patients who underwent robotic low anterior resection (LAR) or abdominoperineal resection (APR) for rectal adenocarcinoma between 2010 and 2014. RESULTS: 46 LARs (65%) and 25 APRs (35%) were identified. Median procedure time was 219 minutes (IQR 184-275) and mean blood loss 164.9 cc (SD 155.9 cc). Radial margin was negative in 70/71 (99%) patients. Total mesorectal excision integrity was complete/near complete in 38/39 (97%) of graded specimens. A mean of 16.8 (SD+/- 8.9) lymph nodes were retrieved. At median follow-up of 21.9 months, there were no local recurrences. CONCLUSIONS: Robotic proctectomy for rectal cancer was introduced into typical colorectal surgery practice by a single surgeon, with a low conversion rate, low complication rate, and satisfactory oncologic outcomes.

Single-incision robotic colectomy: are costs prohibitive?

BACKGROUND: The feasibility, safety, and costs of single-incision robotic colectomy (SIRC) are not known. METHODS: A retrospective review was conducted, comparing the initial 29 consecutive SIRC procedures performed to 36 multiport laparoscopic colectomies (MLC). RESULTS: The groups did not differ significantly on age, body mass index, gender, ASA classification, smoking status, steroid usage or rate of diabetes. Procedure time, conversion rate, infectious complications and length of stay did not differ significantly. The ratio of observed:expected direct hospital costs statistically favoured MLC, although there was no statistical difference between groups for contribution margin, or for observed and expected direct hospital costs. CONCLUSIONS: These results demonstrate safety and technical feasibility for SIRC in selected patients with short-term outcomes and hospital costs comparable to MLC. Contribution margin remained positive and expected costs exceeded observed for SIRC. Increased costs for SIRC are a concern. The comparable but relatively high mortality in both groups may represent an institutional approach to colectomy where significant comorbidity is not a contraindication to minimally invasive surgery. Copyright © 2015 John Wiley & Sons, Ltd.

Normal tissue considerations and dose-volume constraints in the moderately hypofractionated treatment of non-small cell lung cancer.

Hypofractionated radiation therapy (RT) regimes in non-small cell lung cancer (NSCLC) have become increasingly popular with a number of international trials currently underway. The majority of the dose-volume-constraints (DVCs) published in the literature refer to conventional 2Gy per fraction deliveries. Here relevant organs-at-risk (OARs) are identified and available dose-volume constraint data discussed and summarised for moderately hypofractionated NSCLC regimes. The OARs examined include lung, brachial plexus, heart, oesophagus, airway and spinal cord. Where available the toxicity rates are also reported with all data summarised tabulated to aid its use in the clinic.