Estimation of the organ of origin of peri-ampullary malignancy by preoperative CT scan.

BACKGROUND: Tumors occurring within the pancreatic head commonly arise from the pancreas, duodenal ampulla, distal bile duct, or duodenum. However, they are difficult to distinguish on standard preoperative imaging. PURPOSE: To assess the ability of specialist reporting of preoperative computed tomography (CT) scans to determine the organ of origin of pancreatic cancer (PC). MATERIAL AND METHODS: Blinded re-reporting of preoperative imaging from five hospitals was undertaken of a consecutive cohort of 411 patients undergoing surgery for PC between January 2006 and May 2014. Radiological identification of tumor site was determined by the presence of the main tumor bulk within the pancreatic head parenchyma and estimation of the pathological organ of origin of the PC was based on all the reported features. RESULTS: Each pathological tumor type was noted to have distinct radiological features. Localization of a visible tumor within the pancreatic parenchyma was seen most commonly in PC (92%) than other tumor types (P < 0.0001). Local invasion into the duodenum was a characteristic feature seen in 79% of patients with ampullary tumors and isolated dilation of the bile duct without dilation of the pancreatic duct was seen most commonly in patients with ampullary or bile duct cancer. In the assessment of tumor origin, good agreement (kappa = 0.6, 0.51-0.68) was noted between the consensus radiology opinion and the final histology result. Overall accuracy was greatest for ampullary cancer (88.1%) and lowest for PC (83.2%). CONCLUSION: Radiological assessment of preoperative imaging provides a high degree of accuracy in predicting the organ of origin of peri-ampullary cancer.

Training and Match Demands of Elite Rugby Union.

ABSTRACT: Cousins, BEW, Morris, JG, Sunderland, C, Bennett, AM, Shahtahmassebi, G, and Cooper, SB. Training and match demands of elite rugby union. J Strength Cond Res 37(1): 141-148, 2023-This study aimed to examine training and match demands associated with elite Rugby Union. Eighty-nine elite players were monitored using subjective (session ratings of perceived exertion) and objective (global positioning systems: distance and high-speed running [defined as >70% of individual maximum speed] distance) methods, alongside key performance indicator variables in matches (e.g., number of tackles made). These were compared between positions (forwards vs. backs) and league of competition (Premiership vs. Championship). Statistical significance was accepted as p < 0.05. Analysis revealed that backs covered greater distance (by 704 m, p < 0.001) in training and greater distance (by 7.6 m·min-1, p < 0.001) and high-speed running distance (by 1.22 m·min-1, p < 0.001) in matches, compared with forwards. In matches, the forwards experience greater key performance indicator demand (tackles: 78%; tackle assists: 207%; breakdown entries: 324%; contact events: 117%; all p < 0.001) compared with backs. The number of tackles (53%, p < 0.001) and tackles missed (35%, p = 0.001) were greater, whereas contact carries (12%, p = 0.010) and breakdown entries (10%, p = 0.024) were lower, in the Premiership compared with the Championship. Overall, these findings confirm that the running demands of Rugby Union are higher in backs, whereas contact actions are higher in forwards, with further differences between the Premiership and Championship. This comprehensive examination of the demands of elite Rugby Union could be used to ensure the specificity of training protocols for elite Rugby Union clubs, specific to both playing position (forward or back) and level of competition (Premiership or Championship).

Variation in survival after surgery for peri-ampullary cancer in a regional cancer network.

BACKGROUND: Centralisation of specialist surgical services requires that patients are referred to a regional centre for surgery. This process may disadvantage patients who live far from the regional centre or are referred from other hospitals by making referral less likely and by delaying treatment, thereby allowing tumour progression. The aim of this study is to explore the outcome of surgery for peri-ampullary cancer (PC) with respect to referring hospital and travel distance for treatment within a network served by five hospitals. METHODS: Review of a unit database was undertaken of patients undergoing surgery for PC between January 2006 and May 2014. RESULTS: 394 patients were studied. Although both the median travel distance for patients from the five hospitals (10.8, 86, 78.8, 54.7 and 89.2 km) (p < 0.05), and the annual operation rate for PC (2.99, 3.29, 2.13, 3.32 and 3.07 per 100,000) (p = 0.044) were significantly different, no correlation was noted between patient travel distance and population operation rate at each hospital. No difference was noted between patients from each hospital in terms of resection completion rate or pathological stage of the resected tumours. The median survival after diagnosis for patients referred from different hospitals ranged from 1.2 to 1.7 years and regression analysis revealed that increased travel distance to the regional centre was associated with a small survival advantage. CONCLUSION: Although variation in the provision and outcome of surgery for PC between regional hospitals is noted, this is not adversely affected by geographical isolation from the regional centre. TRIAL REGISTRATION: This study is part of post-graduate research degree project. The study is registered with ClinicalTrials.gov (unique identifier NCT02296736 ) November 18, 2014.

Rebound growth of hepatic colorectal metastases after neo-adjuvant chemotherapy: effect on survival after resection.

BACKGROUND: A period of recovery is commonly allowed between completion of chemotherapy for colorectal liver metastases (CRLM) and resection, during which tumour progression may occur. The study-aim is to assess the growth of CRLM in this interval and association with outcome. METHOD: Data on 146 patients were analysed. Change in tumour size was assessed by comparing size determined by imaging performed on completion of chemotherapy with that determined by examination of the resected specimen, categorised by RECIST criteria. RESULTS: In the interval before surgery sixteen patients (11%) fulfilled criteria for partial response (PR), 48 (33%) had stable disease (SD) and 82 (56%) had progressive disease (PD). Among patients with PD following chemotherapy the median disease-free survival of patients who initially responded (26 months) was longer than in those who initially had stable disease (7 months) (P = 0.002). No association was noted between rate of tumour growth after completion of chemotherapy and disease-free survival. CONCLUSION: Change in tumour size after completion of chemotherapy is variable and can be rapid, especially in patients who initially respond to treatment. However, disease-free survival is determined by tumour behaviour during treatment and not by change in size after completion of chemotherapy.

Assessment of the effect of interval from presentation to surgery on outcome in patients with peri-ampullary malignancy.

BACKGROUND: Delay between diagnosis of peri-ampullary cancer (PC) and surgery may allow tumour progression and affect outcome. The aim of this study was to explore associations of interval to surgery (IS) with pathological outcomes and survival in patients with PC. METHOD: A database review of all patients undergoing surgery between 2006 and 2014 was undertaken. IS was measured from diagnosis by imaging. Potential association between IS and survival was measured using Cox regression analysis, and between IS and pathological outcome with multivariate logistic analysis. RESULTS: 388 patients underwent surgery. The median IS was 49 days (1-551 days), and was not associated with any of the evaluated outcomes in patients with pancreatic (149) or distal bile duct (46) cancer. For patients with ampullary cancer (71) longer IS was associated with improved survival, with median survival of 27.5 months for patients waiting ≤ median IS (35) and 38.3 months for patients waiting > median IS (36) for surgery (p = 0.041). A higher rate of margin positivity (31.4%) was also noted among patients who waited less than the median IS compared to those waiting longer than this interval (11.4%) (p = 0.032). CONCLUSION: For patients with ampullary cancer there is a paradoxical improvement in outcome among those with a longer IS, which may be explained by progression to inoperability of more aggressive lesions.

Gallbladder ejection fraction declines with age in patients undergoing cholecystectomy for acalculous biliary symptoms but has low accuracy in the prediction of gallbladder pathology.

BACKGROUND/AIMS: Hepatobiliary Iminodiacetic Acid (HIDA) scan provides a technique to quantify gallbladder ejection fraction (EF) in patients suffering acalculous biliary colic (ACBC). We wished to evaluate the accuracy of EF in the prediction of gallbladder pathology in patients undergoing cholecystectomy. METHODS: Data were retrieved from a database of patients referred for HIDA scan for ACBC, including EF and the pathological outcome of those undergoing cholecystectomy, and compared to normal values obtained from a review of related studies. Significant associations were demonstrated by chi-square, Mann-Whitney test, and linear regression. The predictive accuracy of different cut-offs of EF was demonstrated by the ROC curve analysis. RESULTS: Of 83 patients referred for HIDA scan for ACBC, 41 underwent cholecystectomy. The median EF of this group (33%) was significantly lower than the composite normal median value from previous studies (56%). Thirty-two patients revealed evidence of gallbladder pathology. The EF declined with age (coefficient = -0.51, 95% CI = -0.99 to -0.33), but the median value did not differ between those with gallbladder pathology (34%) and those with normal gallbladders (29%). CONCLUSION/DISCUSSION: Although an EF cut-off of 35% had the greatest accuracy in the prediction of pathology of those tested (0.56), the poor negative predictive value (23.5%) was a major contributor to its low accuracy. Although patients with ACBC have reduced gallbladder EF compared to the normal population, its quantitative assessment is of limited value in the prediction of gallbladder pathology.

Socioeconomic status influences the likelihood but not the outcome of liver resection for colorectal liver metastasis.

BACKGROUND: The aim of this study was to compare the socioeconomic profile of patients undergoing liver resection for colorectal liver metastasis (CLM) in a regional hepatopancreatobiliary unit with that of the local population. A further aim was to determine if degree of deprivation is associated with tumour recurrence after resection. METHODS: A retrospective analysis of patients undergoing liver resection for CLM was performed. Geodemographic segmentation was used to divide the population into five categories of socioeconomic status (SES). RESULTS: During a 7-year period, 303 patients underwent resection for CLM. The proportion of these patients in the two least deprived categories of SES was greater than that of the local population (50.2% versus 40.2%) and the proportion in the two most deprived categories was lower (18.3% versus 30.1%) (P < 0.001). There was no difference in recurrence rate (P = 0.867) or disease-free survival among categories of SES (P = 0.913). Multivariate analysis demonstrated no association between SES and tumour recurrence (P = 0.700). CONCLUSIONS: Liver resection for CLM is performed more commonly among the least socioeconomically deprived population than among the most deprived. However, degree of deprivation was not associated with tumour recurrence after resection.

Extended pathology reporting of resection specimens of colorectal liver metastases: the significance of a tumour pseudocapsule.

INTRODUCTION: The aim of this study was to analyse the influence of factors reported in the minimum histopathology dataset for colorectal liver metastases (CRLM) and other pre-operative factors compared with additional data relating to the presence of tumour pseudocapsules and necrosis on recurrence 1 year after a resection. METHODS: For a period of 14 months, extended histological reporting of CRLM specimens was performed, including the presence of pseudocapsules and necrosis in each tumour. The details of recurrence were obtained from surveillance imaging. RESULTS: In 66 patients there were 27 recurrences within 1 year. The rates were lower for patients with tumour pseudocapsules (8/27) than for patients without (19/36) (P = 0.030). Pseudocapsules were associated with a younger age (P = 0.005), nodal stage of the primary colorectal tumour (P = 0.025) and metachronous tumours (P = 0.004). In patients with synchronous disease and pseudocapsules, the recurrence rate was 2/12 compared with 13/23 patients without pseudocapsules (P = 0.026). DISCUSSION: These findings demonstrate that histological examination of resection specimens can provide significant additional prognostic information for patients after resection of CRLM, compared with clinical and radiological data. The present finding that the absence of a pseudocapsule in patients with synchronous CRLM is associated with a dramatically worse outcome may help direct patient-specific adjuvant treatment and care.

Population density and spreading of COVID-19 in England and Wales.

We investigated daily COVID-19 cases and deaths in the 337 lower tier local authority regions in England and Wales to better understand how the disease propagated over a 15-month period. Population density scaling models revealed residual variance and skewness to be sensitive indicators of the dynamics of propagation. Lockdowns and schools reopening coincided with increased variance indicative of conditions with local impact and country scale heterogeneity. University reopening and December holidays reduced variance indicative of country scale homogenisation which reached a minimum in mid-January 2021. Homogeneous propagation was associated with better correspondence with normally distributed residuals while heterogeneous propagation was more consistent with skewed models. Skewness varied from strongly negative to strongly positive revealing an unappreciated feature of community propagation. Hot spots and super-spreading events are well understood descriptors of regional disease dynamics that would be expected to be associated with positively skewed distributions. Positively skewed behaviour was observed; however, negative skewness indicative of "cold-spots" and "super-isolation" dominated for approximately 8 months during the period of study. In contrast, death metrics showed near constant behaviour in scaling, variance, and skewness metrics over the full period with rural regions preferentially affected, an observation consistent with regional age demographics in England and Wales. Regional positions relative to density scaling laws were remarkably persistent after the first 5-9 days of the available data set. The determinants of this persistent behaviour probably precede the pandemic and remain unchanged.

Synthetic playing surfaces increase the incidence of match injuries in an elite Rugby Union team.

OBJECTIVES: To examine differences in match injury incidence between three playing surfaces in elite Rugby Union. DESIGN: Prospective cohort. METHODS: Match injury incidence was assessed in 89 elite Rugby Union players over two-seasons of professional competition (44 matches, 1014 h player exposure). Match injury incidence was assessed on three different playing surfaces; natural grass, hybrid (natural grass combined with approximately 3% synthetic fibres) and fully synthetic (sand and rubber infill). Overall injury incidence, contact and non-contact injury incidence, and the incidence of minor (≤7 d lost) and major (≥8 d lost) injuries were considered using mixed effect models. RESULTS: Overall match injury incidence doubled on hybrid and synthetic surfaces compared to natural grass (hybrid: OR = 2.58 [95% CI 1.65-4.03], p < 0.001; synthetic: OR = 2.16 [95% CI 1.07-4.37], p = 0.033). Furthermore, the odds of sustaining a contact injury on a pitch containing any synthetic content also increased compared to natural grass (hybrid: OR = 2.31 [95% CI 1.41-3.78], p = 0.001; synthetic: OR = 2.19 [95% CI 1.00-4.77], p = 0.049). The hybrid surface elicited a four times greater likelihood of non-contact injury incidence compared to natural grass (OR = 4.18 [95% CI 1.16-15.04], p = 0.028). However, the playing surface did not affect the severity of match injuries (all p > 0.05). CONCLUSIONS: The present study suggests that even a small percentage (3%) of synthetic content in the playing surface significantly increases match injury incidence, with an effect seen on both contact and non-contact injury incidence. These findings are important to enable practitioners to be aware of the injury implications of playing matches on hybrid and synthetic pitches.

Statistical models for identifying frequent hitters in high throughput screening.

High throughput screening (HTS) interrogates compound libraries to find those that are "active" in an assay. To better understand compound behavior in HTS, we assessed an existing binomial survivor function (BSF) model of "frequent hitters" using 872 publicly available HTS data sets. We found large numbers of "infrequent hitters" using this model leading us to reject the BSF for identifying "frequent hitters." As alternatives, we investigated generalized logistic, gamma, and negative binomial distributions as models for compound behavior. The gamma model reduced the proportion of both frequent and infrequent hitters relative to the BSF. Within this data set, conclusions about individual compound behavior were limited by the number of times individual compounds were tested (1-1613 times) and disproportionate testing of some compounds. Specifically, most tests (78%) were on a 309,847-compound subset (17.6% of compounds) each tested ≥ 300 times. We concluded that the disproportionate retesting of some compounds represents compound repurposing at scale rather than drug discovery. The approach to drug discovery represented by these 872 data sets characterizes the assays well by challenging them with many compounds while each compound is characterized poorly with a single assay. Aggregating the testing information from each compound across the multiple screens yielded a continuum with no clear boundary between normal and frequent hitting compounds.

Rural-urban scaling of age, mortality, crime and property reveals a loss of expected self-similar behaviour.

The urban scaling hypothesis has improved our understanding of cities; however, rural areas have been neglected. We investigated rural-urban population density scaling in England and Wales using 67 indicators of crime, mortality, property, and age. Most indicators exhibited segmented scaling about a median critical density of 27 people per hectare. Above the critical density, urban regions preferentially attract young adults (25-40 years) and lose older people (> 45 years). Density scale adjusted metrics (DSAMs) were analysed using hierarchical clustering, networks, and self-organizing maps (SOMs) revealing regional differences and an inverse relationship between excess value of property transactions and a range of preventable mortality (e.g. diabetes, suicide, lung cancer). The most striking finding is that age demographics break the expected self-similarity underlying the urban scaling hypothesis. Urban dynamism is fuelled by preferential attraction of young adults and not a fundamental property of total urban population.

From remote sensing and machine learning to the history of the Silk Road: large scale material identification on wall paintings.

Automatic remote reflectance spectral imaging of large painted areas in high resolution, from distances of tens of meters, has made the imaging of entire architectural interior feasible. However, it has significantly increased the volume of data. Here we present a machine learning based method to automatically detect 'hidden' writings and map material variations. Clustering of reflectance spectra allowed materials at inaccessible heights to be properly identified by performing non-invasive analysis on regions in the same cluster at accessible heights using a range of complementary spectroscopic techniques. The world heritage site of the Mogao caves, along the ancient Silk Road, consists of 492 richly painted Buddhist cave temples dating from the fourth to fourteenth century. Cave 465 at the northern end of the site is unique in its Indo-Tibetan tantric Buddhist style, and like many other caves, the date of its construction is still under debate. This study demonstrates the powers of an interdisciplinary approach that combines material identification, palaeographic analysis of the revealed Sanskrit writings and archaeological evidence for the dating of the cave temple paintings, narrowing it down to the late twelfth century to thirteenth century.

Match and Training Load Exposure and Time-Loss Incidence in Elite Rugby Union Players.

OBJECTIVE: To investigate the impact of match and training load on time-loss incidence in elite, professional Rugby Union players. MATERIALS AND METHODS: Eighty-nine Rugby Union players were monitored over two seasons of training and competition. Load was measured for all training sessions and matches using subjective [session ratings of perceived exertion (sRPE) load; RPE × session duration] and objective [global positioning systems (GPS); distance and high-speed running distance] methods and quantified using multiple approaches; absolute match and training load, acute:chronic workload ratio (ACWR), exponentially weighted moving average (EWMA) and cumulative 7, 14, 21, and 28 d sums. Mixed effect models were used to assess the effect of each variable on time-loss incidence. RESULTS: Of the 474 time-loss incidences that occurred across the two seasons, 50.0% were contact injuries (86.5% occurred during matches and 13.5% during training), 34.8% were non-contact injuries (31.5% occurred during matches and 68.5% during training) and 15.2% were cases of illness. The absolute match and training load variables provided the best explanation of the variance in time-loss incidence occurrence [sRPE load: p < 0.001, Akaike information criterion (AIC) = 2936; distance: p < 0.001, AIC = 3004; high-speed running distance: p < 0.001, AIC = 3025]. The EWMA approach (EWMA sRPE load: p < 0.001, AIC = 2980; EWMA distance: p < 0.001, AIC = 2980; EWMA high-speed running distance: p = 0.002, AIC = 2987) also explained more of the variance in time-loss incidence occurrence than the ACWR approach (ACWR sRPE load: p = 0.091, AIC = 2993; ACWR distance: p = 0.008, AIC = 2990; ACWR high-speed running distance: p = 0.153, AIC = 2994). CONCLUSION: Overall, the absolute sRPE load variable best explained the variance in time-loss incidence, followed by absolute distance and absolute high-speed running distance. Whilst the model fit using the EWMA approach was not as good as the absolute load variables, it was better than when the same variables were calculated using the ACWR method. Overall, these findings suggest that the absolute match and training load variables provide the best predictors of time-loss incidence rates, with sRPE load likely to be the optimal variant of those examined here.

Serum arterial lactate concentration predicts mortality and organ dysfunction following liver resection.

BACKGROUND: The aim of this study was to determine if the post-operative serum arterial lactate concentration is associated with mortality, length of hospital stay or complications following hepatic resection. METHODS: Serum lactate concentration was recorded at the end of liver resection in a consecutive series of 488 patients over a seven-year period. Liver function, coagulation and electrolyte tests were performed post-operatively. Renal dysfunction was defined as a creatinine rise of >1.5x the pre-operative value. RESULTS: The median lactate was 2.8 mmol/L (0.6 to 16 mmol/L) and was elevated (≥2 mmol/L) in 72% of patients. The lactate concentration was associated with peak post-operative bilirubin, prothrombin time, renal dysfunction, length of hospital stay and 90-day mortality (P < 0.001). The 90-day mortality in patients with a post-operative lactate ≥6 mmol/L was 28% compared to 0.7% in those with lactate ≤2 mmol/L. Pre-operative diabetes, number of segments resected, the surgeon's assessment of liver parenchyma, blood loss and transfusion were independently associated with lactate concentration. CONCLUSIONS: Initial post-operative lactate concentration is a useful predictor of outcome following hepatic resection. Patients with normal post-operative lactate are unlikely to suffer significant hepatic or renal dysfunction and may not require intensive monitoring or critical care.