Strongyloides colitis, a rare but important mimic of Crohn's disease, resulting in coma and multi-organ failure: a case report.

BACKGROUND: Strongyloides colitis is a severe form of strongyloidiasis that carries a high mortality rate if untreated. There is an overlapping clinical presentation between Strongyloides colitis and Crohn's disease. Here, we present a case of a patient who was diagnosed with Crohn's disease and was treated with immunosuppressant therapy which resulted in a poor outcome. CASE PRESENTATION: A middle-aged, native African male presented with diarrhea, abdominal pain, and weight loss. Colonoscopy showed some patchy inflammation in the caecum, which on biopsy was suggestive of Crohn's disease. He had a short course of steroids before being admitted to an emergency with abdominal pain, diarrhea, malnutrition, and severe weight loss. Initial conservative treatment failed, and he became acutely unwell and septic with peritonitis. Laparotomy was carried out, which showed mild inflammation in the terminal ileum, which was not resected. Postoperatively, the patient became comatose and went into multi-organ dysfunction. He failed to progress, and a further laparotomy and subtotal colectomy were performed on the 12th postoperative day. His multi-organ failure progressed, and he succumbed to death 4 days later. DISCUSSION: Strongyloides stercoralis is a parasite causing an enteric infection in animals and humans. Strongyloidiasis in immunocompetent individuals is usually an indolent disease. However, in immunocompromised individuals, it can cause hyperinfective syndrome. Patients with strongyloid colitis should undergo colonoscopy and biopsy where acute inflammation with eosinophilic infiltrates indicates parasitic infiltration of the colonic wall. Surgery is generally not indicated, and any surgical intervention with misdiagnosis of a flare-up of IBD can be very detrimental to the patient. CONCLUSION: Strongyloid colitis can very harmfully mimic Crohn's colitis, and the use of steroids and immunosuppressants can disseminate parasitic infection. Hyperinfection syndrome can lead to sepsis, organ dysfunction, and comma. Disseminated infection carries a high mortality.

A Systematic Review and Meta-analysis Examining the Impact of Age on Perioperative Inflammatory Biomarkers.

BACKGROUND: Dysregulation of immune responses to surgical stress in older patients and those with frailty may manifest as differences in inflammatory biomarkers. We conducted a systematic review and meta-analysis to examine differences in perioperative inflammatory biomarkers between older and younger patients, and between patients with and without frailty. METHODS: MEDLINE, Embase, Cochrane, and CINAHL databases were searched (Inception to June 23, 2020). Observational or experimental studies reporting the perioperative level or activity of biomarkers in surgical patients stratified by age or frailty status were included. The primary outcome was inflammatory biomarkers (grouped by window of ascertainment: pre-op; post-op: <12 hours, 12-24 hours, 1-3 days, 3 days to 1 week, and >1 week). Quality assessment was conducted using the Newcastle-Ottawa Scale. Inverse-variance, random-effects meta-analysis was conducted. RESULTS: Forty-five studies (4263 patients) were included in the review, of which 36 were pooled for meta-analysis (28 noncardiac and 8 cardiac studies). Two studies investigated frailty as the exposure, while the remaining investigated age. In noncardiac studies, older patients had higher preoperative levels of interleukin (IL)-6 and C-reactive protein (CRP), lower preoperative levels of lymphocytes, and higher postoperative levels of IL-6 (<12 hours) and CRP (12-24 hours) than younger patients. In cardiac studies, older patients had higher preoperative levels of IL-6 and CRP and higher postoperative levels of IL-6 (<12 hours and >1 week). CONCLUSIONS: Our findings demonstrate a paucity of frailty-specific studies; however, the presence of age-associated differences in the perioperative inflammatory response is consistent with age-associated states of chronic systemic inflammation and immunosenescence. Additional studies assessing frailty-specific changes in the systemic biologic response to surgery may inform the development of targeted interventions.

The impact of pre-operative biologic therapy on post-operative surgical outcomes in ulcerative colitis: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Biologic therapy has emerged as an effective modality amongst the medical treatment options available for ulcerative colitis (UC). However, its impact on post-operative care in patients with UC is still debatable. This review evaluates the risk of post-operative complications following biologic treatment in patients with UC. METHODS: A systematic search of the relevant databases was conducted with the aim of identifying studies that compared the post-operative complication rates of UC patients who were either exposed or not exposed to a biologic therapy prior to their surgery. Outcomes of interest included both infection-related complications and overall surgical morbidity. Pooled odds-ratio (OR) and 95% confidence intervals (CI) were calculated using Review Manager 5.3. RESULTS: In all, 20 studies, reviewing a total of 12,494 patients with UC, were included in the meta-analysis. Of these, 2254 patients were exposed to a biologic therapy prior to surgery. The pooled ORs for infection-related complications (n = 8067) and overall complications (n = 11,869) were 0.98 (95% CI 0.66-1.45) and 1.14 (95% CI 1.04-1.28), respectively, which suggested that there was no significant association between the use of pre-operative biologic therapy and post-operative complications. Interestingly, the interval between the last dose of biologic therapy and surgery did not influence the risk of having a post-operative infection. CONCLUSIONS: This meta-analysis suggests that pre-operative biologic therapy does not increase the overall risk of having post-operative infection-related or other complications. PROSPERO registration id-CRD42019141827.

Predictors of postoperative respiratory complications in children undergoing adenotonsillectomy.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is commonly treated with adenotonsillectomy (AT), bringing risk of perioperative respiratory adverse events (PRAEs). We aimed to concurrently identify clinical and polysomnographic predictors of PRAEs in children undergoing AT. METHODS: Retrospective study of children undergoing AT at a tertiary-care pediatric hospital, with prior in-hospital polysomnography, January 2010 to December 2016. PRAEs included those requiring oxygen, jaw thrust, positive airway pressure, or mechanical ventilation. Relationships of PRAEs to preoperative comorbidities or polysomnography results were examined with univariable logistic regression. Variables with P < .1 and age were included in backward stepwise multivariable logistic regression. Predictive performance (area under the curve, AUC) was validated with bootstrap resampling. RESULTS: Analysis included 374 children, median age 6.1 years; 286 (76.5%) had ≥ 1 comorbidity. 344 (92.0%) had sleep-disordered breathing; 232 (62.0%) moderate-severe; 66 (17.6%) had ≥ 1 PRAE. PRAEs were more frequent in children with craniofacial, genetic, cardiac, airway anomaly, or neurological conditions, AHI ≥ 5 events/h and oxygen saturation nadir ≤ 80% on preoperative polysomnography. Prediction modeling identified cardiac comorbidity (odds ratio [OR] 2.09 [1.11, 3.89]), airway anomaly (OR 3.19 [1.33, 7.49]), and younger age (OR < 3 years: 4.10 (1.79, 9.26; 3 to 6 years: 2.21 [1.18, 4.15]) were associated with PRAEs (AUC 0.74; corrected AUC 0.68). CONCLUSIONS: Prediction modeling concurrently evaluating comorbidities and polysomnography metrics identified cardiac disease, airway anomaly, and young age as independent predictors of PRAEs. These findings suggest that medical comorbidity and age are more important factors in predicting PRAEs than PSG metrics in a medically complex population.

Fibroblast growth factor 7 signalling is disrupted in colorectal cancer and is a potential marker of field cancerisation.

BACKGROUND: Field cancerisation proposes that there are pre-malignant genetic mutations in the macroscopically normal mucosal tissue around colorectal cancer. This study aims to evaluate fibroblast growth factor 7 (FGF7) tissue expression in the mucosal field around colorectal cancer. METHODS: Gene and protein expression of FGF7, its receptor, FGFR2 and its downstream targets; FRS2α, Erk 1/2 and Akt was measured from mucosal samples in 34 control subjects and 17 cancer patients. Serial samples from tumour, adjacent to tumour and at the resection margin were utilised. RESULTS: FGF7 gene expression was significantly higher in tumour (2.3-fold), adjacent mucosa (3.2-fold) and resection margin (2.8-fold) of cancer patients compared with control subjects (P<0.01 respectively). However, FGFR2 was down regulated (3.5-fold) in the tumour tissue (P<0.001). Protein expression of FRS2α and Akt was significantly lower in tumour tissue compared with the resection margin in cancer patients (P<0.05 respectively). No differences in protein expression of Erk 1/2 were detected. CONCLUSIONS: FGF7 was elevated in the mucosal field of cancer patients supporting its potential as a biomarker of field cancerisation. Changes in FRS2α, Akt and Erk 1/2 expression in the tumour tissue indicate that with malignant transformation, FGF7 loses its ability to regulate cellular differentiation.

Reporting preclinical anesthesia study (REPEAT): Evaluating the quality of reporting in the preclinical anesthesiology literature.

Poor reporting quality may contribute to irreproducibility of results and failed 'bench-to-bedside' translation. Consequently, guidelines have been developed to improve the complete and transparent reporting of in vivo preclinical studies. To examine the impact of such guidelines on core methodological and analytical reporting items in the preclinical anesthesiology literature, we sampled a cohort of studies. Preclinical in vivo studies published in Anesthesiology, Anesthesia & Analgesia, Anaesthesia, and the British Journal of Anaesthesia (2008-2009, 2014-2016) were identified. Data was extracted independently and in duplicate. Reporting completeness was assessed using the National Institutes of Health Principles and Guidelines for Reporting Preclinical Research. Risk ratios were used for comparative analyses. Of 7615 screened articles, 604 met our inclusion criteria and included experiments reporting on 52 490 animals. The most common topic of investigation was pain and analgesia (30%), rodents were most frequently used (77%), and studies were most commonly conducted in the United States (36%). Use of preclinical reporting guidelines was listed in 10% of applicable articles. A minority of studies fully reported on replicates (0.3%), randomization (10%), blinding (12%), sample-size estimation (3%), and inclusion/exclusion criteria (5%). Statistics were well reported (81%). Comparative analysis demonstrated few differences in reporting rigor between journals, including those that endorsed reporting guidelines. Principal items of study design were infrequently reported, with few differences between journals. Methods to improve implementation and adherence to community-based reporting guidelines may be necessary to increase transparent and consistent reporting in the preclinical anesthesiology literature.

An in-silico quality assurance study of contouring target volumes in thoracic tumors within a cooperative group setting.

INTRODUCTION: Target delineation variability is a significant technical impediment in multi-institutional trials which employ intensity modulated radiotherapy (IMRT), as there is a real potential for clinically meaningful variances that can impact the outcomes in clinical trials. The goal of this study is to determine the variability of target delineation among participants from different institutions as part of Southwest Oncology Group (SWOG) Radiotherapy Committee's multi-institutional in-silico quality assurance study in patients with Pancoast tumors as a "dry run" for trial implementation. METHODS: CT simulation scans were acquired from four patients with Pancoast tumor. Two patients had simulation 4D-CT and FDG-FDG PET-CT while two patients had 3D-CT and FDG-FDG PET-CT. Seventeen SWOG-affiliated physicians independently delineated target volumes defined as gross primary and nodal tumor volumes (GTV_P & GTV_N), clinical target volume (CTV), and planning target volume (PTV).Six board-certified thoracic radiation oncologists were designated as the 'Experts' for this study. Their delineations were used to create a simultaneous truth and performance level estimation (STAPLE) contours using ADMIRE software (Elekta AB, Sweden 2017). Individual participants' contours were then compared with Experts' STAPLE contours. RESULTS: When compared to the Experts' STAPLE, GTV_P had the best agreement among all participants, while GTV_N showed the lowest agreement among all participants. There were no statistically significant differences in all studied parameters for all TVs for cases with 4D-CT versus cases with 3D-CT simulation scans. CONCLUSIONS: High degree of inter-observer variation was noted for all target volume except for GTV_P, unveiling potentials for protocol modification for subsequent clinically meaningful improvement in target definition. Various similarity indices exist that can be used to guide multi-institutional radiotherapy delineation QA credentialing.

Use of lung treatment plans to evaluate DIR algorithms.

The purpose of the study is to evaluate the accuracy of two deformable image registration algorithms by examining their influence on the dose summation results obtained using 4DCT (four dimensional computed tomography) dose distributions based on '4D' planned and '4D optimal' IMRT (intensity modulated radiation therapy) plans. For ten lung cancer patients, 4D step and shoot IMRT plans were produced. The breathing cycle was divided into ten parts and for each part a set of CT images was acquired. For each patient the treatment plan was copied to the CTs of each phase and subsequently recalculated. Each phase CT was then registered to the average intensity projection (AIP) CT using a deformable image registration (DIR) algorithm and the composite dose distribution was then calculated by summing up the deformed dose distributions from all the phases ('4D' treatment plan). The '4D optimal' treatment plan was created by producing an optimal plan on the CTs of each phase of the respiratory cycle and summing up the deformed dose distributions from all the phases. The results indicate that it is possible to map the dose distributions of different breathing phases in lung using DIR, and that different DIR methods and target characteristics (motion amplitude, size, location) affect the differences between original plan, '4D' and '4D optimal' dose distributions. Although the '4D optimal' plans were designed to achieve 95% target coverage, both of the used DIR methods failed to translate that coverage in some instances. The same variation between these methods was also observed in the '4D' plan comparison. This study shows that it is feasible to perform an acceptably accurate calculation of the composite deformed dose. However, it is important to account for tumor motion and body deformation especially when the tumor volume is small and/or located in the lower lobe of the lung.

Clinical outcomes and effect of delayed intervention in patients with hollow viscus injury due to blunt abdominal trauma: a systematic review.

INTRODUCTION: Hollow viscus injury (HVI) due to blunt abdominal trauma remains a diagnostic challenge, often presenting late and results in delayed intervention. Despite several treatment algorithms, there is currently no consensus on how to manage patients with HVI. The aim of this review was to define clinical outcomes and the effect of delayed intervention in patients with HVI due to blunt abdominal trauma. The primary outcome of interest was difference in mortality between groups. METHODS: Based on the preferred reporting items for systematic reviews and meta-analyses statement, a literature search was performed. Studies comparing clinical outcomes in adult patients with hollow viscus injury due to blunt abdominal trauma undergoing early or delayed laparotomy were included. Two independent reviewers screened the abstracts. RESULTS: In all, 2288 articles were retrieved. After screening, 11 studies were included. Outcomes in 3812 patients were reported. Overall mortality was 17%. Ten studies reported no difference in mortality between groups. A statistical increase in morbidity was described in five studies, and a trend to increased morbidity was seen in a further two studies. Two studies reported increased mortality in delayed intervention in isolated bowel injury. CONCLUSIONS: This systematic review summarises the results of studies considering outcomes in patients with HVI due to blunt abdominal trauma who have early vs delayed intervention. Overall mortality was significant at 17%. If all patients with hollow viscus injury are considered, the majority of studies do not show an increase in mortality. As patients with isolated bowel injuries have higher mortality in the studies reviewed, to improve outcomes in this subset further investigation is warranted.

Treatment and Outcomes of Primary Urethra Cancer.

BACKGROUND: Urethral cancer is a rare malignancy, representing <1% of all malignancies. Optimal management, due to its rarity, presents as a treatment dilemma for physicians. There is a lack of consensus regarding treatment as large randomized trials cannot be performed; thus, optimal management decisions rely on study of retrospective cases. This is a review of our institutional experience with urethral cancer treated with various treatment modalities. METHODS: A retrospective chart review was performed on 31 patients treated for primary cancer of the urethra from 1958 to 2008. The patients were stratified by sex, histologic type, stage, date of diagnosis, type of treatment, and last follow-up. Early stage cases were designated as Tis-T2N0M0 and advanced cases were designated as T3-4, N+ or M+. Analysis was performed based on clinical stage, treatment modalities and outcomes. RESULTS: Fourteen early stage cases and 17 advanced stage cases of urethral cancer were analyzed. The majority of early stage cases occurred in men (M:F=8:6) and the majority of advanced stage cases occurred in women (M:F=5:12). The most common histology was squamous cell carcinoma for both early and advanced stage cases. Surgery was the preferred modality of treatment for early stage cases (surgery used in 13 cases vs. chemo/radiotherapy used in 1 case) while for advanced cases, radiation ±chemotherapy was commonly used. Overall survival for this series was 45% at mean follow-up of 7 years. Eight of the 14 cases of early stage cancer remained disease free at last follow-up. Comparatively, only 5 of 17 with advanced cancers had no apparent disease at last follow-up. All but one of those patients were treated with combined modality therapy. CONCLUSIONS: Patients with early stage urethral cancers do well with single modality therapy, whereas patients who present with advanced cancers may benefit from combined modality therapy. More extensive study is required to recommend a particular treatment protocol. However, in this rare malignancy, institutional experiences provide the best evidence currently due to the lack of multi-institutional trials.

Interventions to improve the outcomes of frail people having surgery: A systematic review.

BACKGROUND: Frailty is an important prognostic factor for adverse outcomes and increased resource use in the growing population of older surgical patients. We identified and appraised studies that tested interventions in populations of frail surgical patients to improve perioperative outcomes. METHODS: We systematically searched Cochrane, CINAHL, EMBASE and Medline to identify studies that tested interventions in populations of frail patients having surgery. All phases of study selection, data extraction, and risk of bias assessment were done in duplicate. Results were synthesized qualitatively per a prespecified protocol (CRD42016039909). RESULTS: We identified 2 593 titles; 11 were included for final analysis, representing 1 668 participants in orthopedic, general, cardiac, and mixed surgical populations. Only one study was multicenter and risk of bias was moderate to high in all studies. Interventions were applied pre- and postoperatively, and included exercise therapy (n = 4), multicomponent geriatric care protocols (n = 5), and blood transfusion triggers (n = 1); no specific surgical techniques were compared. Exercise therapy, applied pre-, or post-operatively, was associated with significant improvements in functional outcomes and improved quality of life. Multicomponent protocols suffered from poor compliance and difficulties in implementation. Transfusion triggers had no significant impact on mortality or other outcomes. CONCLUSIONS: Despite a growing literature that demonstrates strong independent associations between frailty and adverse outcomes, few interventions have been tested to improve the outcomes of frail surgical patients, and most available studies are at substantial risk of bias. Multicenter, low risk of bias, studies of perioperative exercise are needed, while substantial efforts are required to develop and test other interventions to improve the outcomes of frail people having surgery.

Risk factors for metachronous adenoma in the residual colon of patients undergoing curative surgery for colorectal cancer.

PURPOSE: Adenoma detection in colorectal cancer survivors is poorly characterised with insufficient evidence to inform frequency of surveillance schedule. The aim of this study was to examine adenoma incidence and recurrence in patients who have undergone colorectal cancer resection with curative intent. Survival outcomes were compared to determine if the presence of adenomas could be used to identify patients at higher risk of local recurrence. METHODS: This is a retrospective observational cohort study at a single tertiary institution between 2006 and 2012. Five hundred fifteen consecutive patients with stage I-III colorectal cancer who had preoperative colonoscopy and curative surgery were included (median follow-up 56 months (36-75 months). RESULTS: In total, 352/515 (68%) patients underwent postoperative surveillance colonoscopy in the first 5 years after resection. Male gender was associated with greater risk of detecting synchronous adenoma at index colonoscopy or in the resection specimen (OR 2.35, p < 0.001). In the first 5 years after cancer surgery, synchronous adenoma, male gender and right sided primary tumour were independent predictors of metachronous lesions (OR 2.13, p = 0.009; OR 2.07, p = 0.027 and OR 2.34, p = 0.004, respectively). Presence of synchronous or metachronous adenoma had no impact upon incidence of local recurrence, overall or disease free survival. CONCLUSIONS: Patients with synchronous adenoma remain at high risk of adenoma recurrence despite undergoing colonic resection and should be considered for early endoscopic surveillance. Men and those undergoing right-sided resection have a higher risk of metachronous adenoma in the long term and may benefit from more frequent endoscopic surveillance post resection.

'Playing the game': How do surgical trainees seek feedback using workplace-based assessment?

OBJECTIVES: Although trainees and trainers find feedback interactions beneficial, difficulties in giving and receiving feedback are reported. Few studies have explored what drives trainees to seek feedback. This study explores how workplace-based assessments (WBAs) influence the ways surgical trainees seek feedback and feedback interactions. METHODS: Utilising a template analysis approach, we conducted 10 focus groups with 42 surgical trainees from four regions across the UK. Data were independently coded by three researchers, incorporating three a priori themes identified from a previous quantitative study. Further themes emerged from exploration of these data. The final template, agreed by the three researchers, was applied to all focus group transcripts. The themes were linked in a diagrammatical form to allow critical exploration of the data. RESULTS: Trainees' perceptions of the purpose of WBA for learning or an assessment of learning, and their relationship with their trainer impacted upon how trainees chose to use WBA. Perceiving WBA as a test led trainees to 'play the game': seek positive and avoid negative feedback through WBA. Perceiving WBA as a chance to learn led trainees to seek negative feedback. Some trainees sought negative feedback outside WBA. Negative feedback was more important for changing practice compared with positive feedback, which enabled trainees to 'look good' but had less of an effect on changing clinical practice. The timing of feedback relative to WBA was also important, with immediate feedback being more beneficial for learning; however, delayed feedback was still sought using WBA. DISCUSSION: Trainees' perceptions of the purpose of WBA and their relationship with their trainer informed when they chose to seek feedback. Trainees who perceived WBA as a test were led to 'play the game' by seeking positive and avoiding negative feedback. Outside of WBA, trainees sought negative feedback, which was most important for change in practice.

Surgical Trainee Feedback-Seeking Behavior in the Context of Workplace-Based Assessment in Clinical Settings.

PURPOSE: To investigate surgical trainee feedback-seeking behaviors-directly asking for feedback (inquiry) and observing and responding to situational clues (monitoring)-in the context of workplace-based assessment (WBA). METHOD: A hypothetical model of trainee feedback-seeking behavior was developed using existing literature. A questionnaire, incorporating previously validated instruments from organizational psychology, was distributed to general surgical trainees at 23 U.K. hospitals in 2012-2013. Statistical modeling techniques compared the data with 12 predetermined hypothetical relationships between feedback-seeking behaviors and predictive variables (goal orientation, supervisory style) through mediating variables (perceptions of personal benefits and costs of feedback) to develop a final model. RESULTS: Of 235 trainees invited, 178 (76%) responded. Trainees completed 48 WBAs/year on average, and 73% reported receiving feedback via WBA. The final model was of good fit (chi-square/degree of freedom ratio = 1.620, comparative fit index = 0.953, root mean square error of approximation = 0.059). Modeled data showed trainees who perceive personal benefits to feedback use both feedback inquiry and monitoring to engage in feedback interactions. Trainees who seek feedback engage in using WBA. Trainees' goal orientations and perceptions of trainers' supervisory styles as supportive and instrumental are associated with perceived benefits and costs to feedback. CONCLUSIONS: Trainees actively engage in seeking feedback and using WBA. Their perceptions of feedback benefits and costs and supervisory style play a role in their feedback-seeking behavior. Encouraging trainees to actively seek feedback by providing specific training and creating a supportive environment for feedback interactions could positively affect their ability to seek feedback.

Persistent Disparities in Hispanics with Cervical Cancer in a Major City.

OBJECTIVES: Despite an overall improvement in cervical cancer screening, incidence, and mortality rates for minorities in the USA, regional differences in screening and stage at presentation have been observed. This study evaluated cervical cancer disparities in a predominately Hispanic population treated in a major treatment center in San Antonio, Texas. METHODS AND MATERIALS: Data on 446 patients with cervical cancer treated between 2000 and 2011 at the Cancer Therapy and Research Center in San Antonio, Texas, were reviewed. Sufficient information was obtained on 319 patients and was compared with the Surveillance, Epidemiology, and End Results (SEER) data. RESULTS: Of 319 patients treated for cervical cancer between 2000 and 2011, 209 were Hispanics and 110 were Whites (82), Blacks (20), Asians (7), and others (1). The median and mean ages at diagnosis were 47 and 49, respectively. Only 36 % were known to have screening Pap tests prior to diagnosis, of which only 24 had yearly Pap tests. Forty-two patients (20 %) of those with no known screening Pap tests presented with stage IV disease at diagnosis (vs. 3 % of those with known Pap tests). Among the Hispanics, 68 % presented with regional disease (vs. 37 % SEER) and 46 % were stage III or higher disease, with stage IIIB accounting for 30 % of total. Although the overall age-adjusted death rates were higher in Hispanics due to a higher percentage of more advanced disease, survival rates appear similar, stage for stage, to the SEER data. CONCLUSION: Even in a major city, Hispanics often present with more advanced cervical cancer than the general population. In order to minimize the cervical cancer disparities, efforts and strategies are needed to study the cultural and locale effects and to implement preventive measures and adaptive health education.

Assessment of Lung Tumour Motion and Volume Size Dependencies Using Various Evaluation Measures.

The purpose of the study was to assess internal target volume changes through the breathing cycle and associated tumour motion for lung patients and to establish possible correlations between different parameters. Respiration-induced volume changes with breathing cycle and the associated tumour motion were analyzed for 11 patients. Selected phases were the maximum and average intensity projections and the 10 phases of equal duration and separation obtained through the respiratory cycle. Tumour centre of mass (COM) motion planes were generated using least square fitting, and their angles and orientations were then compared between the cases studied. Trajectories that are composed by the points of COM location in different phases were identified, and their interrelation was assessed through different similarity measures. The results were used to determine if there is any correlation between parameters chosen and if the margins conventionally used for the planning target volume creation successfully encompassed lung tumour motion and volume change. The results show that the extent of tumour motion was related to its volume and location. The tumour displacement was predominantly left and inferior. Planar fitting to COM motion data through respiratory phases demonstrated some correlation in best fit motion plane positions between different data sets. In the plane fit comparison, for each patient, the lower root mean square error values showed that a good planar fit can be achieved for the COM motion path. The evaluation of the inhale and exhale trajectories may allow, for certain tumour locations and size, contouring on only inhalation or exhalation phases, knowing that tumour motion will be adequately covered on the other phases. Taking all the data into account and knowing the tumour size and location, a good estimate can be made of the motion plane position in the three-dimensional space and the required dosimetric margins.

Use of Antegrade Continence Enema for the Treatment of Fecal Incontinence and Functional Constipation in Adults: A Systematic Review.

BACKGROUND: Antegrade continence enema is a proximal colonic stoma that allows antegrade lavage of the colon for the treatment of fecal incontinence and functional constipation. Its role in the treatment of these conditions in adults has not been established. OBJECTIVE: This review aimed to evaluate the clinical response and complications of antegrade continence enema in the adult population. DATA SOURCES: A systematic literature search of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases from January 1980 to October 2013 was conducted. STUDY SELECTION: Studies reporting clinical outcomes of antegrade continence enema in adult patients were considered. Only studies with participants aged 16 years and older were selected. INTERVENTION(S): Use of the antegrade continence enema for the treatment of constipation and incontinence in adults was investigated. MAIN OUTCOME MEASURES: The primary outcome was the number of patients irrigating their stoma. Secondary outcomes included the incidence of stoma stenosis, assessment of functional outcome, and evaluation of quality of life. RESULTS: Overall, 15 studies were selected, describing outcomes in 374 patients. All of the reports were observational cross-sectional studies, and 4 were prospective. The number of participants still using their stoma ranged from 47% to 100% over a follow-up period of 6 to 55 months. Eleven studies reported achievement of full continence in 33% to 100% of patients. Four studies described functional outcomes, and 7 studies reported a wide range of patient satisfaction. The rate of stoma stenosis varied from 8% to 50%. LIMITATIONS: There were considerable heterogeneities within and across studies. Most studies were of poor quality, as reflected in the Methodological Index for Nonrandomized Studies score. CONCLUSIONS: Antegrade continence enema has been reported as an acceptable treatment of both functional constipation and fecal incontinence in adults across several analyses. There is wide variation regarding outcome measures. Larger prospective studies are required to assess the role of antegrade continence enema in the adult population.

GRK2 Fine-Tunes Circadian Clock Speed and Entrainment via Transcriptional and Post-translational Control of PERIOD Proteins.

The pacemaker properties of the suprachiasmatic nucleus (SCN) circadian clock are shaped by mechanisms that influence the expression and behavior of clock proteins. Here, we reveal that G-protein-coupled receptor kinase 2 (GRK2) modulates the period, amplitude, and entrainment characteristics of the SCN. Grk2-deficient mice show phase-dependent alterations in light-induced entrainment, slower recovery from jetlag, and longer behavioral rhythms. Grk2 ablation perturbs intrinsic rhythmic properties of the SCN, increasing amplitude and decreasing period. At the cellular level, GRK2 suppresses the transcription of the mPeriod1 gene and the trafficking of PERIOD1 and PERIOD2 proteins to the nucleus. Moreover, GRK2 can physically interact with PERIOD1/2 and promote PERIOD2 phosphorylation at Ser545, effects that may underlie its ability to regulate PERIOD1/2 trafficking. Together, our findings identify GRK2 as an important modulator of circadian clock speed, amplitude, and entrainment by controlling PERIOD at the transcriptional and post-translational levels.

Field cancerisation in colorectal cancer: a new frontier or pastures past?

Despite considerable advances in our understanding of cancer biology, early diagnosis of colorectal cancer remains elusive. Based on the adenoma-carcinoma sequence, cancer develops through the progressive accumulation of mutations in key genes that regulate cell growth. However, recent mathematical modelling suggests that some of these genetic events occur prior to the development of any discernible histological abnormality. Cells acquire pro-tumourigenic mutations that are not able to produce morphological change but predispose to cancer formation. These cells can grow to form large patches of mucosa from which a cancer arises. This process has been termed "field cancerisation". It has received little attention in the scientific literature until recently. Several studies have now demonstrated cellular, genetic and epigenetic alterations in the macroscopically normal mucosa of colorectal cancer patients. In some reports, these changes were effectively utilised to identify patients with a neoplastic lesion suggesting potential application in the clinical setting. In this article, we present the scientific evidence to support field cancerisation in colorectal cancer and discuss important limitations that require further investigation. Characterisation of the field defect is necessary to enable early diagnosis of colorectal cancer and identify molecular targets for chemoprevention. Field cancerisation offers a promising prospect for experimental cancer research and has potential to improve patient outcomes in the clinical setting.

Size and distribution of lymph nodes in rectal cancer resection specimens.

BACKGROUND: The detection of lymph node involvement is fundamental to the staging of rectal cancer, and aids in prognostication and identification of patients who will benefit from adjuvant therapy. The anatomical variation in distribution and size of mesorectal lymph nodes has received scant attention. OBJECTIVE: This study aimed to determine the size and distribution of lymph nodes in rectal cancer resection specimens. DESIGN: This was a prospective, observational study of rectal cancer resection specimens analyzed by a single histopathologist. SETTING: This study was conducted from January 2007 to July 2013 at the authors' institution. PATIENTS: Two hundred forty-four consecutive patients underwent resection for rectal cancer. MAIN OUTCOME MEASURES: The size and distribution of lymph nodes in the resection specimens and the anatomical position of mesorectal lymph nodes in relation to the peritoneal reflection, tumor, and anal verge were recorded. RESULTS: A total of 10,473 lymph nodes were retrieved in 244 patients (75 women; median age, 68 years (interquartile range, 59-75 years)). One hundred seventy-three anterior resection and 71 abdominoperineal resection specimens were analyzed. Median lymph node yield was 41 lymph nodes (interquartile range, 31-52); 344 of 10,473 (3.2%) lymph nodes were positive. Lymph nodes were distributed in the mesorectum, sigmoid mesentery, and vascular pedicle in 40%, 32%, and 28% of the patients. Sixty-eight percent of mesorectal lymph nodes were above the peritoneal reflection. Mesorectal lymph node distribution in relation to the tumor was 53% above, 36% adjacent to, and only 11% below the tumor. Ninety-five of 334 (28%) positive nodes were ≤3 mm in diameter. LIMITATIONS: Resection specimens analyzed by other pathologists (<5%) have not been included, and fat clearance techniques were not used to retrieve lymph nodes. CONCLUSIONS: To ensure accurate nodal staging of rectal cancer, both resection and subsequent pathological evaluation should focus on the mesorectum in close proximity to the tumor and along the superior rectal artery. Small lymph nodes (<3 mm in size) should not be overlooked, and lymph node metastasis to the sigmoid mesentery is rare (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A177).