Safety of robotic cholecystectomy as index training procedure: the UK experience.

AIMS: To evaluate the safety profile of robotic cholecystectomy performed within the United Kingdom (UK) Robotic Hepatopancreatobiliary (HPB) training programme. METHODS: A retrospective evaluation of prospectively collected data from eleven centres participating in the UK Robotic HPB training programme was conducted. All adult patients undergoing robotic cholecystectomy for symptomatic gallstone disease or gallbladder polyp were considered. Bile duct injury, conversion to open procedure, conversion to subtotal cholecystectomy, length of hospital stay, 30-day re-admission, and post-operative complications were the evaluated outcome parameters. RESULTS: A total of 600 patients were included. The median age was 53 (IQR 65-41) years and the majority (72.7%; 436/600) were female. The main indications for robotic cholecystectomy were biliary colic (55.5%, 333/600), cholecystitis (18.8%, 113/600), gallbladder polyps (7.7%, 46/600), and pancreatitis (6.2%, 37/600). The median length of stay was 0 (IQR 0-1) days. Of the included patients, 88.5% (531/600) were discharged on the day of procedure with 30-day re-admission rate of 5.5% (33/600). There were no bile duct injuries and the rate of conversion to open was 0.8% (5/600) with subtotal cholecystectomy rate of 0.8% (5/600). CONCLUSION: The current study confirms that robotic cholecystectomy can be safely implemented to routine practice with a low risk of bile duct injury, low bile leak rate, low conversion to open surgery, and low need for subtotal cholecystectomy.

Quantitative Measure of Lung Structure and Function Obtained from Hyperpolarized Xenon Spectroscopy.

Hyperpolarized Xenon-129 (HXe) magnetic resonance imaging (MRI) provides tools for obtaining 2- or 3-dimensional maps of lung ventilation patterns, gas diffusion, Xenon uptake by lung parenchyma, and other lung function metrics. However, by trading spatial for temporal resolution, it also enables tracing of pulmonary Xenon gas exchange on a ms timescale. This article describes one such technique, chemical shift saturation recovery (CSSR) MR spectroscopy. It illustrates how it can be used to assess capillary blood volume, septal wall thickness, and the surface-to-volume ratio in the alveoli. The flip angle of the applied radiofrequency pulses (RF) was carefully calibrated. Single-dose breath-hold and multi-dose free-breathing protocols were employed for administering the gas to the subject. Once the inhaled Xenon gas reached the alveoli, a series of 90° RF pulses was applied to ensure maximum saturation of the accumulated Xenon magnetization in the lung parenchyma. Following a variable delay time, spectra were acquired to quantify the regrowth of the Xenon signal due to gas exchange between the alveolar gas volume and the tissue compartments of the lung. These spectra were then analyzed by fitting complex pseudo-Voigt functions to the three dominant peaks. Finally, the delay time-dependent peak amplitudes were fitted to a one-dimensional analytical gas-exchange model to extract physiological parameters.

Simultaneous quantification of hyperpolarized xenon-129 ventilation and gas exchange with multi-breath xenon-polarization transfer contrast (XTC) MRI.

PURPOSE: To demonstrate the feasibility of a multi-breath xenon-polarization transfer contrast (XTC) MR imaging approach for simultaneously evaluating regional ventilation and gas exchange parameters. METHODS: Imaging was performed in five healthy volunteers and six chronic obstructive pulmonary disease (COPD) patients. The multi-breath XTC protocol consisted of three repeated schemes of six wash-in breaths of a xenon mixture and four normoxic wash-out breaths, with and without selective saturation of either the tissue membrane or red blood cell (RBC) resonances. Acquisitions were performed at end-exhalation while subjects maintained tidal breathing throughout the session. The no-saturation, membrane-saturation, and RBC-saturation images were fit to a per-breath gas replacement model for extracting voxelwise tidal volume (TV), functional residual capacity (FRC), and fractional ventilation (FV), as well as tissue- and RBC-gas exchange (fMem and fRBC , respectively). The sensitivity of the derived model was also evaluated via simulations. RESULTS: With the exception of FRC, whole-lung averages for all metrics were decreased in the COPD subjects compared to the healthy cohort, significantly so for FV, fRBC , and fMem . Heterogeneity was higher overall in the COPD subjects, particularly for fRBC , fMem , and fRBC:Mem . The anterior-to-posterior gradient associated with the gravity-dependence of lung function in supine imaging was also evident for FV, fRBC , and fMem values in the healthy subjects, but noticeably absent in the COPD cohort. CONCLUSION: Multi-breath XTC imaging generated high-resolution, co-registered maps of ventilation and gas exchange parameters acquired during tidal breathing and with low per-breath xenon doses. Clear differences between healthy and COPD subjects were apparent and consistent with spirometry.

Unsupervised segmentation and quantification of COVID-19 lesions on computed Tomography scans using CycleGAN.

BACKGROUND: Lesion segmentation is a critical step in medical image analysis, and methods to identify pathology without time-intensive manual labeling of data are of utmost importance during a pandemic and in resource-constrained healthcare settings. Here, we describe a method for fully automated segmentation and quantification of pathological COVID-19 lung tissue on chest Computed Tomography (CT) scans without the need for manually segmented training data. METHODS: We trained a cycle-consistent generative adversarial network (CycleGAN) to convert images of COVID-19 scans into their generated healthy equivalents. Subtraction of the generated healthy images from their corresponding original CT scans yielded maps of pathological tissue, without background lung parenchyma, fissures, airways, or vessels. We then used these maps to construct three-dimensional lesion segmentations. Using a validation dataset, Dice scores were computed for our lesion segmentations and other published segmentation networks using ground truth segmentations reviewed by radiologists. RESULTS: The COVID-to-Healthy generator eliminated high Hounsfield unit (HU) voxels within pulmonary lesions and replaced them with lower HU voxels. The generator did not distort normal anatomy such as vessels, airways, or fissures. The generated healthy images had higher gas content (2.45 ± 0.93 vs 3.01 ± 0.84 L, P < 0.001) and lower tissue density (1.27 ± 0.40 vs 0.73 ± 0.29 Kg, P < 0.001) than their corresponding original COVID-19 images, and they were not significantly different from those of the healthy images (P < 0.001). Using the validation dataset, lesion segmentations scored an average Dice score of 55.9, comparable to other weakly supervised networks that do require manual segmentations. CONCLUSION: Our CycleGAN model successfully segmented pulmonary lesions in mild and severe COVID-19 cases. Our model's performance was comparable to other published models; however, our model is unique in its ability to segment lesions without the need for manual segmentations.

Deriving Regionally Specific Biomarkers of Emphysema and Small Airways Disease Using Variable Threshold Parametric Response Mapping on Volumetric Lung CT Images.

PURPOSE: This study aims to develop and validate a parametric response mapping (PRM) methodology to accurately identify diseased regions of the lung by using variable thresholds to account for alterations in regional lung function between the gravitationally-independent (anterior) and gravitationally-dependent (posterior) lung in CT images acquired in the supine position. METHODS: 34 male Sprague-Dawley rats (260-540 g) were imaged, 4 of which received elastase injection (100 units/kg) as a model for emphysema (EMPH). Gated volumetric CT was performed at end-inspiration (EI) and end-expiration (EE) on separate groups of free-breathing (n = 20) and ventilated (n = 10) rats in the supine position. To derive variable thresholds for the new PRM methodology, voxels were first grouped into 100 bins based on the fractional distance along the anterior-to-posterior direction. Lower limits of normal (LLN) for x-ray attenuation in each bin were set by determining the smallest region that enclosed 98% of voxels from healthy, ventilated animals. RESULTS: When utilizing fixed thresholds in the conventional PRM methodology, a distinct posterior-anterior gradient was seen, in which nearly the entire posterior region of the lung was identified as HEALTHY, while the anterior lung was labeled as significantly less so (t(29) = -3.27, p = 0.003). In both cohorts, %SAD progressively increased from posterior to anterior, while %HEALTHY lung decreased in the same direction. After applying our PRM methodology with variable thresholds to the same rat images, the posterior-anterior trend in %SAD quantification was removed from all rats and the significant increase of diseased lung in the anterior was removed. CONCLUSIONS: The PRM methodology using variable thresholds provides regionally specific markers of %SAD and %EMPH by correcting for alterations in regional lung function associated with the naturally occurring vertical gradient of dependent vs. non-dependent lung density and compliance.

Impact of SARS-CoV-2 pandemic on pancreatic cancer services and treatment pathways: United Kingdom experience.

INTRODUCTION: The SARS-CoV-2 pandemic presented healthcare providers with an extreme challenge to provide cancer services. The impact upon the diagnostic and treatment capacity to treat pancreatic cancer is unclear. This study aimed to identify national variation in treatment pathways during the pandemic. METHODS: A survey was distributed to all United Kingdom pancreatic specialist centres, to assess diagnostic, therapeutic and interventional services availability, and alterations in treatment pathways. A repeating methodology enabled assessment over time as the pandemic evolved. RESULTS: Responses were received from all 29 centres. Over the first six weeks of the pandemic, less than a quarter of centres had normal availability of diagnostic pathways and a fifth of centres had no capacity whatsoever to undertake surgery. As the pandemic progressed services have gradually improved though most centres remain constrained to some degree. One third of centres changed their standard resectable pathway from surgery-first to neoadjuvant chemotherapy. Elderly patients, and those with COPD were less likely to be offered treatment during the pandemic. CONCLUSION: The COVID-19 pandemic has affected the capacity of the NHS to provide diagnostic and staging investigations for pancreatic cancer. The impact of revised treatment pathways has yet to be realised.

The in situ near-total pancreatectomy (LIVOCADO procedure) for end-staged chronic pancreatitis.

PURPOSE: Total pancreatectomy for severe pain in end-stage chronic pancreatitis may be the only option, but with vascular involvement, this is usually too high risk and/or technically not feasible. The purpose of the study was to present the clinical outcomes of a novel procedure in severe chronic pancreatitis complicated by uncontrollable pain and vascular involvement. METHODS: We describe an in situ near-total pancreatectomy that avoids peripancreatic vascular dissection (Livocado procedure) and report on surgical and clinical outcomes. RESULTS: The Livocado procedure was carried out on 18 (3.9%) of 465 patients undergoing surgery for chronic pancreatitis. There were 13 men and 5 women with a median (IQR) age of 48.5 (42.4-57) years and weight of 60.7 (58.0-75.0) kg. All had severe pain and vascular involvement; 17 had pancreatic parenchymal calcification; the median (IQR) oral morphine equivalent dose requirement was 86 (33-195) mg/day. The median (IQR) maximal pain scores were 9 (9-10); the average pain score was 6 (IQR 4-7). There was no peri-operative or 90-day mortality. At a median (IQR) follow-up of 32.5 (21-45.75) months, both maximal and average pain scores were significantly improved post-operatively, and at 12 months, two-thirds of patients were completely pain free. Six (33%) patients had employment pre-operatively versus 13 (72%) post-operatively (p = 0.01). CONCLUSIONS: The Livocado procedure was safe and carried out successfully in patients with chronic pancreatitis with vascular involvement where other procedures would be contraindicated. Perioperative outcomes, post-operative pain scores, and employment rehabilitation were comparable with other procedures carried out in patients without vascular involvement.

Measuring pulmonary gas exchange using compartment-selective xenon-polarization transfer contrast (XTC) MRI.

PURPOSE: To demonstrate the feasibility of generating red blood cell (RBC) and tissue/plasma (TP)-specific gas-phase (GP) depolarization maps using xenon-polarization transfer contrast (XTC) MR imaging. METHODS: Imaging was performed in three healthy subjects, an asymptomatic smoker, and a chronic obstructive pulmonary disease (COPD) patient. Single-breath XTC data were acquired through a series of three GP images using a 2D multi-slice GRE during a 12 s breath-hold. A series of 8 ms Gaussian inversion pulses spaced 30 ms apart were applied in-between the images to quantify the exchange between the GP and dissolved-phase (DP) compartments. Inversion pulses were either centered on-resonance to generate contrast, or off-resonance to correct for other sources of signal loss. For an alternative scheme, inversions of both RBC and TP resonances were inserted in lieu of off-resonance pulses. Finally, this technique was extended to a multi-breath protocol consistent with tidal breathing, involving 30 consecutive acquisitions. RESULTS: Inversion pulses shifted off-resonance by 20 ppm to mimic the distance between the RBC and TP resonances demonstrated selectivity, and initial GP depolarization maps illustrated stark magnitude and distribution differences between healthy and diseased subjects that were consistent with traditional approaches. CONCLUSION: The proposed DP-compartment selective XTC MRI technique provides information on gas exchange between all three detectable states of xenon in the lungs and is sufficiently sensitive to indicate differences in lung function between the study subjects. Investigated extensions of this approach to imaging schemes that either minimize breath-hold duration or the overall number of breath-holds open avenues for future research to improve measurement accuracy and patient comfort.

Multibreath Hyperpolarized 3He Imaging Scheme to Measure Alveolar Oxygen Tension and Apparent Diffusion Coefficient.

RATIONALE AND OBJECTIVES: In this study, we compared a newly developed multibreath simultaneous alveolar oxygen tension and apparent diffusion coefficient (PAO2-ADC) imaging sequence to a single-breath acquisition, with the aim of mitigating the compromising effects of intervoxel flow and slow-filling regions on single-breath measurements, especially in chronic obstructive pulmonary disease (COPD) subjects. MATERIALS AND METHODS: Both single-breath and multibreath simultaneous PAO2-ADC imaging schemes were performed on a total of 10 human subjects (five asymptomatic smokers and five COPD subjects). Estimated PAO2 and ADC values derived from the different sequences were compared both globally and regionally. The distribution of voxels with nonphysiological values was also compared between the two schemes. RESULTS: The multibreath protocol decreased the ventilation defect volumes by an average of 12.9 ± 6.6%. The multibreath sequence generated nonphysiological PAO2 values in 11.0 ± 8.5% fewer voxels than the single-breath sequence. Single-breath PAO2 maps also showed more regions with gas-flow artifacts and general signal heterogeneity. On average, the standard deviation of the PAO2 distribution was 16.5 ± 7.0% lower using multibreath PAO2-ADC imaging, suggesting a more homogeneous gas distribution. Both mean and standard deviation of the ADC increased significantly from single- to multibreath imaging (p = 0.048 and p = 0.070, respectively), suggesting more emphysematous regions in the slow-filling lung. CONCLUSION: Multibreath PAO2-ADC imaging provides superior accuracy and efficiency compared to previous imaging protocols. PAO2 and ADC maps generated by multibreath imaging allowed for the qualification of various regions as emphysematous or obstructed, which single-breath PAO2 maps can only identify as defects. The simultaneous PAO2 and ADC measurements generated by the presented multibreath method were also more physiologically realistic, and allowed for more detailed analysis of the slow-filling regions characteristic of COPD subjects.

A Model for Predicting Future FEV1 Decline in Smokers Using Hyperpolarized 3He Magnetic Resonance Imaging.

RATIONALE AND OBJECTIVES: The purpose of this study was to assess the effectiveness of hyperpolarized helium-3 magnetic resonance (MR)-based imaging markers in predicting future forced expiratory volume in one second decline/chronic obstructive pulmonary disorder progression in smokers compared to current diagnostic techniques. MATERIALS AND METHODS: Total 60 subjects (15 nonsmokers and 45 smokers) participated in both baseline and follow-up visits (∼1.4 years apart). At both visits, subjects completed pulmonary function testing, a six-minute walk test , and the St. George Respiratory Questionnaire. Using helium-3 MR imaging, means (M) and standard deviations (H) of oxygen tension (PAO2), fractional ventilation, and apparent diffusion coefficient were calculated across 12 regions of interest in the lungs. Subjects who experienced FEV1 decline >100 mL/year were deemed "decliners," while those who did not were deemed "sustainers." Nonimaging and imaging prediction models were generated through a logistic regression model, which utilized measurements from sustainers and decliners. RESULTS: The nonimaging prediction model included the St. George Respiratory Questionnaire total score, diffusing capacity of carbon monoxide by the alveolar volume (DLCO/VA), and distance walked in a six-minute walk test. A receiving operating character curve for this model yielded a sensitivity of 75% and specificity of 68% with an overall area under the curve of 65%. The imaging prediction model generated following the same methodology included ADCH, FVH, and PAO2H. The resulting receiving operating character curve yielded a sensitivity of 87.5%, specificity of 82.8%, and an area under the curve of 89.7%. CONCLUSION: The imaging predication model generated from measurements obtained during 3He MR imaging is better able to predict future FEV1 decline compared to one based on current clinical tests and demographics. The imaging model's superiority appears to arise from its ability to distinguish well-circumscribed, severe disease from a more uniform distribution of moderately altered lung function, which is more closely associated with subsequent FEV1 decline.

The diagnostic value of Rosemont and Japanese diagnostic criteria for 'indeterminate', 'suggestive', 'possible' and 'early' chronic pancreatitis.

BACKGROUND: Longitudinal data are lacking to support consensus criteria for diagnosing early chronic pancreatitis. METHODS: Retrospective single centre study of the initial evidence for chronic pancreatitis (CP), with reassessment after follow-up (January 2003-November 2016). RESULTS: 807 patients were previously diagnosed with chronic pancreatitis. This diagnosis was rejected in 118 patients: 52 had another pathology altogether, the remaining 66 patients formed the study population. 38 patients with 'normal' imaging were reclassified as chronic abdominal pain syndrome (CAPS), and 28 patients had minimal change features of CP on EUS (MCEUS) but never progressed. Strict application of the Japanese diagnostic criteria would diagnose only two patients with early CP and eleven as possible CP. Patients were more likely to have MCEUS if the EUS was performed within 12 months of an attack of acute pancreatitis. 40 patients with MCEUS were identified, including an additional 12 who progressed to definite CP after a median of 30 (18.75-36.5) months. Those continuing to consume excess alcohol and/or continued smoking were significantly more likely to progress. Those who progressed were more likely to develop pancreatic exocrine insufficiency, require pancreatic surgery and had higher mortality. CONCLUSION: There needs to be more stringent application of the systems used for diagnosing chronic pancreatitis with revision of the current terminology 'indeterminate', 'suggestive', 'possible', and 'early' chronic pancreatitis. All patients with MCEUS features of CP require ongoing clinical follow up of at least 30 months and all patients with these features should be strongly counselled regarding smoking cessation and abstinence from alcohol.

Aurora B suppresses microtubule dynamics and limits central spindle size by locally activating KIF4A.

Anaphase central spindle formation is controlled by the microtubule-stabilizing factor PRC1 and the kinesin KIF4A. We show that an MKlp2-dependent pool of Aurora B at the central spindle, rather than global Aurora B activity, regulates KIF4A accumulation at the central spindle. KIF4A phosphorylation by Aurora B stimulates the maximal microtubule-dependent ATPase activity of KIF4A and promotes its interaction with PRC1. In the presence of phosphorylated KIF4A, microtubules grew more slowly and showed long pauses in growth, resulting in the generation of shorter PRC1-stabilized microtubule overlaps in vitro. Cells expressing only mutant forms of KIF4A lacking the Aurora B phosphorylation site overextended the anaphase central spindle, demonstrating that this regulation is crucial for microtubule length control in vivo. Aurora B therefore ensures that suppression of microtubule dynamic instability by KIF4A is restricted to a specific subset of microtubules and thereby contributes to central spindle size control in anaphase.

Melanoma-associated mutations in protein phosphatase 6 cause chromosome instability and DNA damage owing to dysregulated Aurora-A.

Mutations in the PPP6C catalytic subunit of protein phosphatase 6 (PP6) are drivers for the development of melanoma. Here, we analyse a panel of melanoma-associated mutations in PPP6C and find that these generally compromise assembly of the PP6 holoenzyme and catalytic activity towards a model substrate. Detailed analysis of one mutant, PPP6C-H114Y, in both primary melanoma and engineered cell lines reveals it is destabilized and undergoes increased proteasome-mediated turnover. Global analysis of phosphatase substrates by mass spectrometry identifies the oncogenic kinase Aurora-A as the major PP6 substrate that is dysregulated under these conditions. Accordingly, cells lacking PPP6C or carrying the PPP6C-H114Y allele have elevated Aurora-A kinase activity and display chromosome instability with associated Aurora-A-dependent micronucleation. Chromosomes mis-segregated to these micronuclei are preferentially stained by the DNA damage marker γ-H2AX, suggesting that loss of PPP6C promotes both chromosome instability and DNA damage. These findings support the view that formation of micronuclei rather than chromosome instability alone explains how loss of PPP6C, and more generally mitotic spindle and centrosome defects, can act as drivers for genome instability in melanoma and other cancers.

Spinal Epidural Abscess Presenting with Paraplegia Following Delayed Presentation of Traumatic Esophageal Perforation without Spinal Fracture: Lessons to be Learnt.

We describe a case of esophageal perforation following blunt chest trauma with delayed presentation as paraplegia secondary to spinal epidural abscess formation. The case highlights the importance of the awareness of the possibility of esophageal injury in patients following road traffic collisions.

Should oesophagectomies be performed by trainees? The experience from a single teaching centre under the supervision of one surgeon.

INTRODUCTION: Surgical training is threatened by anxieties about trainees performing major procedures. We have analysed the outcome of oesophagectomies performed by a consultant surgeon and compared these to the performance of trainees (years 4-6) operating under direct supervision. PATIENTS AND METHODS: Data were collected retrospectively in a computerised database on all patients who underwent oesophagectomy at a teaching tertiary centre between December 1997 and April 2004 with a minimum 15 months' follow-up. Analysis of outcome was according to measures of technical adequacy, postoperative course, histological analysis, recurrence and survival. RESULTS: During the study period, 241 oesophagectomies were carried out; 157 (65.1%) of these procedures were performed by the consultant and 84 (34.9%) were performed by surgeons-in-training under direct consultant supervision. Pre-operative, technical adequacy, postoperative course, histological analysis, recurrence and survival were comparable in both groups. CONCLUSIONS: These data demonstrate comparable patient outcome when suitably experienced trainees are supervised in performing oesophagectomies and support its continued use in operative training.