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MicroIC enables display attributes unattainable from polycrystalline thin‐film transistors, and the complimentary metal‐oxide semiconductor (CMOS) microICs support a wide range of applications beyond driving pixels. Integrating sensors within displays can add value to products, reduce costs and improve performance versus conventional solutions. As evidenced by touch and display integration in mobile displays via TDDI ICs, in‐cell sensing can reduce cost and improve performance to levels that are not available with all display types. Capacitive touch, optical touch, 3D scanning, and proximity sensing can also benefit from the inherent coordination between sensors and display. We present multiple sensing architectures and demonstrations of integration within microLED displays and describe CMOS microIC circuits for touch sensing applications. With diverse heterogenous semiconductor technology tightly woven into displays, the potential for intuitive gesture controls, adaptive interfaces, and enhanced sensory feedback paves the way for more natural and effortless interactions between humans and machines. [ABSTRACT FROM AUTHOR]

In water‐stressed hyperarid basins, questions mount over the impacts of anthropogenic groundwater extraction and climate‐driven perturbations on groundwater‐surface water interactions and the resilience of ecosystem‐critical surface water. Coupling groundwater with surface water observations from Sentinel‐2 data provides an unprecedented opportunity to evaluate surface water connectivity with local aquifers following intense precipitation events in arid basins. Surface water area and groundwater level data were analyzed for trends following precipitation, including peak lag time, post‐peak recession rates, and changes in hydraulic gradients. Results indicate variable connectivity following large precipitation events between surface water change and groundwater level fluctuations in the upgradient freshwater aquifer, whereas the downgradient brine‐to‐brackish area of the aquifer indicated virtually no connectivity with the aquifer. Comparison between precipitation and surface water response indicate distinct responses based on the physical relationship of the surface water body with the brine‐to‐brackish area of the aquifer. Lumped parameter modeling of surface water inundation also constrains the possible hydrologic dynamics of the post‐precipitation response. While modeled influx to surface water seems primarily controlled by watershed hydraulics rather than direct hydraulic connectivity of the aquifers, the relationship between surface water and adjacent groundwater levels coupled with surface water area indicates that local aquifers are primarily connected to the surface water bodies through discharge via subsurface infiltration. Modeling results imply that the existence of brine‐adjacent surface water in arid basins relies on upgradient discharge from freshwater aquifers. Our results further support that marginal surface water systems can serve as a critical recharge mechanism to local aquifers. Plain Language Summary: Surface water is important for desert ecosystems, but the future of surface water remains uncertain because of climate change and human consumption. Understanding how surface water responds to precipitation and interacts with groundwater is useful for better predicting future water availability. Advancements in the quality of satellite imagery provide an opportunity to combine satellite data with rain gauge and water level data to investigate the connection of surface water to rainfall patterns and groundwater. Observations from flooding behavior show two different types of surface water. Both types can be categorized by proximity to the brine that exists in the aquifer underlying the basin floor: transitional pools occur at the edge of the transition to brine while terminal lagoon systems occur in the brackish groundwater zone. Calculations indicate that the two groups have different inflow and outflow mechanisms that occur over varying timescales. These mechanisms indicate that intense rainfall events will lead to increased inundation over longer periods of time for transitional surface water bodies. However, despite rapid rates of recession, terminal pools will also experience prolonged inundation above background levels for up to a year after large rainfall events because of increased spring discharge from rainfall‐driven recharge to groundwater. Key Points: Post‐precipitation inflow and outflow mechanisms of salar‐adjacent surface water are distinct from recharge and discharge in local aquifersSurface water response to precipitation can be predicted and categorized based on its position to the brine groundwater and the salt flatSurface water resilience to drought relies on groundwater discharge from upgradient springs in hyperarid basins [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to investigate associations between mode of presentation; categorized as emergency, suspected cancer outpatient referral pathway (2-week wait or 2WW pathway), non-cancer suspected outpatient referral (non-2-week wait pathway) or following screening, and stage of diagnosis and survival in patients with colorectal cancer in England. Methods: This was a retrospective cohort observational study of patients diagnosed with colorectal cancer between January 2010 and December 2014 in England using data from Public Health England collated from regional cancer registries. Results: The most common route to diagnosis among 167,501 patients diagnosed with colorectal cancer was via the non-cancer suspect (non-2WW) outpatient referral pathway (35.1%) followed by the suspected cancer (2WW) referral pathway (31.6%), emergency presentation (22.8%) and most infrequently following screening (10.6%) (p < 0.01). Screening confers the greatest likelihood of early-stage diagnosis (61.6%) compared to other modes of presentation. The 5-year overall survival was 81.8%, 53.3%, 53.0% and 27.6% in those diagnosed via screening, 2WW, non-2WW pathway and emergency presentation, respectively. Patients from most deprived regions were more likely to be diagnosed following emergency presentation (27.7 vs 19.7%, p < 0.01) and less likely via screening (8.1 vs 12%, p < 0.01). Conclusions: Asymptomatic individuals diagnosed following screening have earlier stage cancers and better survival, the opposite was observed in those diagnosed following emergency presentation. Patients referred via the 2WW pathway do not have better survival outcomes when compared to those referred via the non-2WW pathway. In addition, this study has identified socio-economic groups that need to be targeted with public health campaigns to improve screening uptake. [ABSTRACT FROM AUTHOR]

Background: Pre-treatment tumour-associated lymphocytes (TILs) and stromal lymphocytes (SLs) are independent predictive markers of future pathological complete response (pCR) in HER2-positive breast cancer. Whilst studies have correlated baseline lymphocyte levels with subsequent pCR, few have studied the impact of neoadjuvant therapy on the immune environment. Methods: We performed TIL analysis and T-cell analysis by IHC on the pretreatment and 'On-treatment' samples from patients recruited on the Phase-II TCHL (NCT01485926) clinical trial. Data were analysed using the Wilcoxon signed-rank test and the Spearman rank correlation. Results: In our sample cohort (n = 66), patients who achieved a pCR at surgery, post-chemotherapy, had significantly higher counts of TILs (p = 0.05) but not SLs (p = 0.08) in their pre-treatment tumour samples. Patients who achieved a subsequent pCR after completing neo-adjuvant chemotherapy had significantly higher SLs (p = 9.09 × 10–3) but not TILs (p = 0.1) in their 'On-treatment' tumour biopsies. In a small cohort of samples (n = 16), infiltrating lymphocyte counts increased after 1 cycle of neo-adjuvant chemotherapy only in those tumours of patients who did not achieve a subsequent pCR. Finally, reduced CD3 + (p = 0.04, rho = 0.60) and CD4 + (p = 0.01, rho = 0.72) T-cell counts in 'On-treatment' biopsies were associated with decreased residual tumour content post-1 cycle of treatment; the latter being significantly associated with increased likelihood of subsequent pCR (p < 0.01). Conclusions: The immune system may be 'primed' prior to neoadjuvant treatment in those patients who subsequently achieve a pCR. In those patients who achieve a pCR, their immune response may return to baseline after only 1 cycle of treatment. However, in those who did not achieve a pCR, neo-adjuvant treatment may stimulate lymphocyte influx into the tumour. [ABSTRACT FROM AUTHOR]

Background: Multicystic peritoneal mesothelioma (MCPM) is a rare neoplasm, generally considered a borderline malignancy, best treated by cytoreductive surgery (CRS) to remove macroscopic disease, combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Owing to its rarity, little has been published on clinical presentation, clinical behaviour over time, or an optimal treatment approach. Methods: A prospectively developed peritoneal malignancy database was interrogated for the years 2001-2018. Details on all patients with MCPM as a definitive diagnosis after CRS and HIPEC were analysed, including previous interventions, mode of presentation, surgical treatment, postoperative outcomes, and late follow-up information from abdominal CT and tumour markers. Results: Some 40 patients with MCPM underwent CRS and HIPEC between 2001 and 2018. Of these, 32 presented with abdominal pain, distension or bloating, six patients presented with recurrence following previous surgery at the referring hospitals, and two had coincidental diagnoses during a surgical procedure. CRS involved peritonectomy in all 40 patients. Bowel resection was required in 18 patients, and seven had a temporary stoma. Thirty-eight patients were considered to have undergone a complete macroscopic tumour removal (completeness of cytoreduction CC0), and two had residual tumour nodules less than 2.5 mm in size, classified as CC1. Median duration of follow-up was 65 (range 48-79) months. There were no deaths during follow-up. The Kaplan-Meier-predicted recurrence-free interval was 115.4 months. Conclusion: MCPM is a rare peritoneal neoplasm with a heterogeneous pattern of presentation. CRS and HIPEC is an effective management option for this group of patients, with favourable long-term survival. [ABSTRACT FROM AUTHOR]

The Salar de Atacama contains one of the world's most important lithium resources and hosts unique and fragile desert ecosystems. Water use issues of the hyper‐arid region have placed it at the center of global attention. This work combines geochemical and hydrogeologic data with remote sensing analysis to address differences in water zones in the marginal environments of the salar. Water samples from across the inflow to brine transition were collected over the period 2012–2016 and analyzed for ẟD, 3H, 87Sr/86Sr and major and minor elements. The ẟD values range from about −64‰ to +20‰, 3H as Rmod from 0.01 to 0.36 and the 87Sr/86Sr from 0.70750 to 0.70804 with highest ẟD and 3H occurring in the regions of open water. Geochemical modeling results indicate inflow and shallow transition zone waters are saturated with respect to calcite, whereas all others are saturated with respect to calcite, gypsum, and halite. Long‐term remote‐sensing of surface water body extents indicate that extreme precipitation events are the primary driver of surface area changes as exemplified by an increase in size of the lagoons by a factor of 2.7 after a storm. A new conceptual model of the freshwater to brine transition zone that incorporates variability in aquifer geology, hydrology and geochemistry to explain important marginal water bodies is presented. The subsurface brines in the transition zone and the halite nucleus are geochemically distinct compared to the groundwater discharge features (e.g., lagoons) over modern time scales which aids in conceptualizing the transition zone system. Plain Language Summary: Salar (salt flat or playa) systems are of intense global focus because of associated water and resource issues. The freshwater‐brine systems that are unique to these areas support important ecosystems as well as both resource development and community needs. This study includes a novel integrated analysis to demonstrate how the water bodies in the marginal zones of salars are controlled by the amount of fresh water flowing from higher elevation below the ground surface, the properties of the complex subsurface geology, and climate variability. The focus is on how freshwater recharge influences physical and chemical properties of marginal water bodies including springs, wetlands, lagoons, and transitional pools. In addition, the two types of brines found in the marginal zone and from the center of the Salar de Atacama are distinct and evidently disconnected from the shallow groundwater discharge features. The methods and approach from this work are transferrable to salar systems on a global scale and can be used by multiple stakeholders for decision making regarding resources and environment where an understanding of these water bodies is needed in assessing local and regional water use. Key Points: Distinct hydrogeologic and geochemical zones are inherent in salar freshwater‐brine systemsLagoons in the Transition Zone are perched by complex subsurface geology, depend on inflow waters, and respond to climate over timeTransition zone brines are geochemically distinct from nucleus brines and are hosted by a more geologically diverse aquifer system [ABSTRACT FROM AUTHOR]

Summary: Background: Dimethyl fumarate (DMF) is the active ingredient of Skilarence™ and Tecfidera™, which are used for the treatment of psoriasis and multiple sclerosis, respectively. Various immunomodulatory mechanisms of action have been identified for DMF; however, it is still unclear what effects DMF exerts in vivo in patients with psoriasis. Objectives: In this study we examined the effects of DMF, both in vivo and in vitro, on T cells, which play a key role in the pathogenesis of psoriasis. Methods: The frequency of T‐cell subsets was examined by flow cytometry in untreated patients with psoriasis or those treated with DMF. The effects of DMFin vitro on T‐cell survival, activation and proliferation, and cell‐surface thiols were assessed by flow cytometry. Results: In patients with psoriasis treated with DMF we observed an increase in the frequency of T regulatory (Treg) cells and a decrease in T helper (Th)17 lineage cells and the associated cytokines interleukin‐17, interleukin‐22 and granulocyte–macrophage colony‐stimulating factor. T cells cultured in vitro with DMF exhibited reduced viability, and inhibition of activation and proliferation in response to stimulation due to the oxidative effects of DMF. However, the frequency of Treg cells increased in the presence of DMF due to their heightened ability to resist DMF‐induced oxidative stress. Conclusions: DMF enhanced the ratio of Treg cells to Th17 cells in patients with psoriasis, in patients with multiple sclerosis and in vitro. Furthermore, our data suggest that this is at least in part as a result of the differential effects of DMF on Treg cells compared with conventional T cells. What is already known about this topic? Dimethyl fumarate is an effective treatment for psoriasis and multiple sclerosis.T cells play a key role in the pathogenesis of psoriasis, and the Treg–Th17 cell axis is dysregulated.Multiple mechanisms of action have been described for DMF; however, its effects on T cells in patients with psoriasis have not been elucidated. What does this study add? The Treg to Th17 ratio was enhanced in patients with psoriasis treated with DMF.DMF also increased the ratio of Treg cells to Th17 cells in vitro, by increasing the frequency of Treg cells.Treg cells exhibited an increased ability to resist the oxidative stress induced by DMF in vitro; this is a new mechanism of action for DMF. What is the translational message? The Treg–Th17 axis is known to be dysregulated in psoriasis, and this study indicates that DMF can modulate this axis in favour of regulation.The ability of Treg cells to resist the oxidative stress induced by DMF is likely to contribute to its mechanism of action.The selective reduction of Th17 cells without a reduction in Th1 cells or Treg cells explains the efficacy of DMF in psoriasis. Linked Comment: Mostafa et al. Br J Dermatol 2021; 184:389–390. Plain language summary available online [ABSTRACT FROM AUTHOR]

Aim: In patients with low rectal cancer it is occasionally necessary to avoid a low coloanal anastomosis due to patient frailty or poor function. In such situations there are two alternative approaches: Hartmann's procedure (HP) or intersphincteric abdominoperineal excision (IAPE). There are few data to guide surgeons as to which of these two procedures is the safest. The aim of this study was to determine the surgical complication rates associated with each procedure. Method: This was a multicentre, nonrandomized prospective cohort study of patients undergoing either HP or IAPE. The primary objective was to determine surgical complication rates. Secondary objectives included length of stay, time to adjuvant therapy and quality of life at 90 days. Results: One hundred and seventy nine patients were recruited between April 2016 and June 2019; approximately two thirds of patients underwent HP and one third IAPE. The overall complication rate was high in both groups (54% for the HP group and 52% for the IAPE group). Surgery‐specific complication rates were also high, but not significantly different: 43% for HP and 48% for IAPE. The pelvic abscess rate in HP was 11% and was significantly higher in patients with a palpable staple line (15% vs 2%). There was a higher incidence of serious medical complications following IAPE (16% vs 5%), along with a reduction in 90‐day quality of life scores. Conclusion: This is the largest prospective study to compare HP and IAPE in patients undergoing rectal cancer surgery where primary anastomosis is not deemed appropriate. With similar complication rates, these data support the ongoing use of either HP or IAPE in this patient group. [ABSTRACT FROM AUTHOR]

Summary: The skin is one of the most important organs in the body, providing integrity and acting as a barrier to exclude microbes, allergens and chemicals. However, chronic skin inflammation can result when barrier function is defective and immune responses are dysregulated or misdirected against harmless or self‐antigens. During the last 15 years interleukin (IL)‐17 cytokines have emerged as key players in multiple inflammatory disorders, and they appear to be especially prominent in skin inflammation. IL‐17 cytokines produced by T cells and other cell types potently activate keratinocytes to promote inflammation in a feed‐forward loop. Given this key pathogenic role of the IL‐17 pathway in autoimmune and inflammatory disease, it has been the focus of intense efforts to target therapeutically. The inflammatory effects of IL‐17 can be targeted directly by blocking the cytokine or its receptor, or indirectly by blocking cytokines upstream of IL‐17‐producing cells. Psoriasis has been the major success story for anti‐IL‐17 drugs, where they have proven more effective than in other indications. Hidradenitis suppurativa (HS) is another inflammatory skin disease which, despite carrying a higher burden than psoriasis, is poorly recognized and under‐diagnosed, and current treatment options are inadequate. Recently, a key role for the IL‐17 pathway in the pathogenesis of HS has emerged, prompting clinical trials with a variety of IL‐17 inhibitors. In this review, we discuss the roles of IL‐17A, IL‐17F and IL‐17C in psoriasis and HS and the strategies taken to target the IL‐17 pathway therapeutically. [ABSTRACT FROM AUTHOR]

Study Question: Which transcriptomic alterations in mid-luteal endometrial scratch biopsies, taken prior to the assisted reproductive treatment (ART) treatment cycle are associated with unsuccessful pregnancy?Summary Answer: Dysregulated interleukin-17 (IL-17) pathway components are demonstrated in women who fail to become pregnant after ART.What Is Known Already: Implantation failure is now recognised as a critical factor in unexplained infertility and may be an important component of failed ART.Study Design, Size, Duration: Using a prospective longitudinal study design, 29 nulliparous women with unexplained infertility undergoing ART were recruited between October 2016 and February 2018. Mid-luteal stage endometrium and matched serum samples were collected, and patients underwent a single embryo transfer in the subsequent cycle. RNA-seq analysis of endometrial biopsies was performed on the discovery cohort (n = 20).Participants/materials, Setting, Methods: Gene set enrichment analysis of the differentially expressed genes (DEGs) was performed. Endometrium and serum were then prepared for IL-17A analysis by ELISA.Main Results and the Role Of Chance: There were 204 differentially expressed protein-coding genes identified in tissue from women who became pregnant (n = 9) compared with tissue from women who failed to become pregnant (n = 11) (false discovery rate; P < 0.05). Of the 204 DEGs, 166 were decreased while 38 were increased in the pregnant compared to the non-pregnant groups. Gene set enrichment analysis of the DEGs identified an over-representation of IL-17 and Pl3K-Akt signalling pathways. All the DEGs within the IL-17 signalling pathway (MMP3, MMP1, IL1β, LCN2, S100A9 and FOSL1) demonstrated decreased expression in the pregnant group. Serum IL-17 protein levels were increased in the non-pregnant discovery cohort (n = 11) and these findings were confirmed a validation cohort (n = 9).Limitations, Reasons For Caution: Limitations of our study include the cohort size and the lack of aneuploidy data for the embryos; however, all embryos transferred were single good or top-quality blastocysts.Wider Implications Of the Findings: These findings demonstrate dysregulated IL-17 pathway components in women who fail to become pregnant after ART. Elevated serum levels of the pro-inflammatory cytokine IL-17 may predict failure of ART in women with unexplained infertility. Future trials of anti-IL-17 therapies in this cohort warrant further investigation.Study Funding/competing Interest(s): Funding from the UCD Wellcome Institutional Strategic Support Fund, which was financed jointly by University College Dublin and the SFI-HRB-Wellcome Biomedical Research Partnership (ref 204844/Z/16/Z), is acknowledged. The authors have no competing interests.Trial Registration Number: NA. [ABSTRACT FROM AUTHOR]

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Aim: Continuity of the mesentery has recently been established and may provide an anatomical basis for optimal colorectal resectional surgery. Preliminary data from operative specimen measurements suggest there is a tapering in the mesentery of the distal sigmoid. A mesenteric waist in this area may be a risk factor for local recurrence of colorectal cancer. This study aimed to investigate the anatomical characteristics of the mesentery at the colorectal junction. Method: In this cross‐sectional study, 20 patients were recruited. After planned colorectal resection, the surgical specimens were scanned in a MRI system and subsequently dissected and photographed as per national pathology guidelines. Mesenteric surface area and linear measurements were compared between MRI and pathology to establish the presence and location of a mesenteric waist. Results: Specimen analysis confirmed that a narrowing in the mesenteric surface area was consistently apparent at the rectosigmoid junction. Above the anterior peritoneal reflection, the surface area and posterior distance of the mesentery of the upper rectum initially decreased before increasing as the mesentery of the sigmoid colon. These anatomical properties created the appearance of a mesenteric 'waist' at the rectosigmoid junction. Using the anterior reflection as a reference landmark, the rectosigmoid waist occurred at a mean height of 23.6 and 21.7 mm on MRI and pathology, respectively. Conclusion: A rectosigmoid waist occurs at the junction of the mesorectum and mesocolon, and is a mesenteric landmark for the rectum that is present on both radiology and pathology. [ABSTRACT FROM AUTHOR]

The impact of threading dislocation density on Ni/n-GaN Schottky barrier diode characteristics is investigated using forward biased current-voltage-temperature (I-V-T) and internal photoemission (IPE) measurements. Nominally, identical metal-organic chemical vapor deposition grown GaN layers were grown on two types of GaN templates on sapphire substrates to controllably vary threading dislocation density (TDD) from 3×107 to 7×108 cm-2. I-V-T measurements revealed thermionic emission to be the dominant transport mechanism with ideality factors near 1.01 at room temperature for both sample types. The Schottky barrier heights showed a similar invariance with TDD, with measured values of 1.12–1.13 eV obtained from fitting the I-V-T results to a thermionic emission-diffusion model. The I-V-T results were verified by IPE measurements made on the same diodes, confirming that the Ni/n-GaN barrier heights do not show a measurable TDD dependence for the TDD range measured here. In apparent contrast to this result is that the measured forward bias I-V characteristics indicate a shift in the observed forward bias turn-on voltage such that at the higher TDD value investigated here, a larger turn-on voltage (lower current) is observed. This difference is attributed to localized current blocking by high potential barrier regions surrounding threading dislocations that intersect the Ni/GaN interface. A simple model is presented that reconciles both the observed voltage shift and variations in the extracted Richardson constant as a function of threading dislocation density. With this model, an average local barrier surrounding dislocation of ∼0.2 V is obtained, which diverts current flow across the forward biased Schottky interface to nondislocated regions. [ABSTRACT FROM AUTHOR]

We report on an extensive study of the two-dimensional electron gas (2DEG) structures containing AlN layers. It is shown that the presence of large polarization fields in the AlN barrier layer in AlN/GaN heterostructures results in high values of the 2DEG sheet density of up to 3.6×10[sup 13] cm[sup -2]. Room-temperature sheet resistance of 180 Ω/□ is demonstrated in the AlN/GaN structure with a 35 Å AlN barrier. As a result of reduced alloy disorder scattering, low-temperature electron mobility is significantly enhanced in AlN/GaN heterostructures in comparison to AlGaN/GaN structures with similar values of the 2DEG sheet density. The growth of GaN cap layers on top of AlN/GaN structures with relatively thick (∼35 Å) AlN barriers is found to lead to a significant decrease in the 2DEG sheet density. However, inserting a thin (∼10 Å) AlN layer between Al[sub x]Ga[sub 1-x]N and GaN in the Al[sub x]Ga[sub 1-x]N/GaN (x∼0.2–0.45) 2DEG structures does not affect the 2DEG sheet density and results in an increase of the low-temperature electron mobility in comparison to standard AlGaN/GaN structures. At room temperature, a combination of the high 2DEG sheet density of 2.15×10[sup 13] cm[sup -2] and high electron mobility of 1500 cm[sup 2]/V s in Al[sub 0.37]Ga[sub 0.63]N/AlN/GaN yielded a low sheet resistance value of 194 Ω/□. © 2001 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Two schemes of nucleation and growth of gallium nitride on Si(111) substrates are investigated and the structural and electrical properties of the resulting films are reported. Gallium nitride films grown using a 10-500 nm-thick AlN buffer layer deposited at high temperature (∼1050 °C) are found to be under 260-530 MPa of tensile stress and exhibit cracking, the origin of which is discussed. The threading dislocation density in these films increases with increasing AlN thickness, covering a range of 1.1 to >5.8x10[sup 9] cm[sup -2]. Films grown using a thick, AlN-to-GaN graded buffer layer are found to be under compressive stress and are completely crack free. Heterojunction field effect transistors fabricated on such films result in well-defined saturation and pinch-off behavior with a saturated current of ∼525 mA/mm and a transconductance of ∼100 mS/mm in dc operation. © 2001 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Aim: Intra‐abdominal fibromatosis is an unusual mesenchymal tumour that can be locally aggressive without any metastatic potential. Fibromatosis may simulate cancer recurrence on imaging surveillance for colorectal cancer follow‐up. The optimal treatment of recurrent peritoneal malignancy is cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Confirmatory biopsy of lesions suspicious for colorectal cancer recurrence may not be feasible, thereby rendering surgery the safest option. Our aim was to determine the incidence of fibromatosis in a cohort of patients undergoing CRS and HIPEC for suspected colorectal cancer recurrence. Methods: One hundred and seventy‐one CRS and HIPEC cases were performed at our Peritoneal Malignancy Institute between February 2007 and October 2018 for colorectal peritoneal metastases and were included in a prospectively maintained database. Results: A total of 49 (29%) of 171 cases were performed for primary colorectal cancer with peritoneal metastases, whereas 122 (71%) of 171 cases were performed for suspected colorectal cancer recurrence detected on surveillance imaging after primary colorectal cancer resection. On histological analysis of the resected specimen, five (4.1%) of 122 cases undergoing CRS and HIPEC for colorectal recurrence had fibromatosis. Conclusion: Fibromatosis can masquerade as colorectal cancer recurrence. In this series it occurred with an incidence of 4.1% among a cohort of patients undergoing CRS and HIPEC for probable recurrence. Surgical resection may be the only option to confirm the diagnosis and rule out malignancy. [ABSTRACT FROM AUTHOR]

Objective The purpose of the present work was to develop evidence-based indications for Mohs micrographic surgery in patients with a diagnosis of skin cancer. Methods The guideline was developed by Cancer Care Ontario’s Program in Evidence-Based Care, together with the Melanoma Disease Site Group and the Surgical Oncology Program, through a systematic review of relevant literature, patient- and caregiver-specific consultation, and internal and external reviews. Recommendation 1 Given a lack of high-quality, comparative evidence, surgery (with postoperative or intraoperative margin assessment) or radiation (for those who are ineligible for surgery) should remain the standard of care for patients with skin cancer. Recommendation 2 Mohs micrographic surgery is recommended for patients with histologically confirmed recurrent basal cell carcinoma of the face and is appropriate for primary basal cell carcinomas of the face that are larger than 1 cm, have aggressive histology, or are located on the H zone of the face. Recommendation 3 Mohs micrographic surgery should be performed by physicians who have completed a degree in medicine or equivalent, including a Royal College of Physicians and Surgeons of Canada Specialist Certificate or equivalent, and have received advanced training in Mohs micrographic surgery. [ABSTRACT FROM AUTHOR]

Background: Patients with peritoneal malignancy often have multiple laparotomies before referral for cytoreductive surgery (CRS). Some have substantial abdominal wall herniation and tumour infiltration of abdominal incisions. CRS involves complete macroscopic tumour removal and hyperthermic intraperitoneal chemotherapy (HIPEC). Abdominal wall reconstruction is problematic in these patients. The aim of this study was to establish immediate and long‐term outcomes of abdominal wall reconstruction with biological mesh in a single centre. Methods: A dedicated peritoneal malignancy database was searched for all patients who had biological mesh abdominal wall reconstruction between 2004 and 2015. Short‐ and long‐term outcomes were reviewed. All patients had annual abdominal CT as routine peritoneal malignancy follow‐up. Results: Some 33 patients (22 women) with a mean age of 53·4 (range 19–82) years underwent abdominal wall reconstruction with biological mesh. The majority (23) had CRS for pseudomyxoma (19 low grade), six for colorectal peritoneal metastasis and four for appendiceal adenocarcinoma; 18 had undergone CRS and HIPEC previously. Twenty‐five of the 33 patients had abdominal wall tumour involvement and eight had concurrent hernias. The mean duration of surgery was 486 (range 120–795) min and the mean mesh size used was 345 (50–654) cm2. Ten patients developed wound infections and four had a seroma. Two developed early enterocutaneous fistulas. Mean follow‐up was 48 months. Five patients developed an incisional hernia. Four died from progressive malignancy. A further 15 patients had disease recurrence, but only one had isolated abdominal wall recurrence. Conclusion: Biological mesh was safe and effective for abdominal wall reconstruction in peritoneal malignancy. Postoperative wound infections were frequent but nevertheless incisional hernia rates were low with no instances of mesh‐related bowel erosion or fistulation. This study of abdominal wall reconstruction in cytoreductive surgery for peritoneal malignancy has demonstrated the long‐term safety and efficacy of biological mesh in this challenging group of patients. Biological mesh safe in peritoneal malignancy [ABSTRACT FROM AUTHOR]

Aim: The concept of significant polyps and early colorectal cancer (SPECC) encompasses complex polyps not amenable to routine snare polypectomy or where malignancy cannot be excluded. Surgical resection (SR) offers definitive treatment, but is overtreatment for the majority which are benign and amenable to less invasive endoscopic resection (ER). The aim of this study was to investigate variations in the management and outcomes of significant colorectal polyps. Method: This was a retrospective observational study of significant colorectal polyps, defined as nonpedunculated lesions of ≥ 20 mm size, diagnosed across nine UK hospitals in 2014. Inclusion criteria were endoscopically or histologically benign polyps at biopsy. Results: A total of 383 patients were treated by primary ER (87.2%) or SR (12.8%). Overall, 108/383 (28%) polyps were detected in the Bowel Cancer Screening Programme (BCSP). Primary SR was associated with a significantly longer length of stay and major complications (P < 0.01). Of the ER polyps, 290/334 (86.8%) patients were treated without undergoing surgery. The commonest indication for secondary surgery was unexpected polyp cancer, and of these cases 60% had no residual cancer in the specimen. Incidence of unexpected cancer was 10.7% (n = 41) and was similar between ER and SR groups (P = 0.11). On multivariate analysis, a polyp size of > 30 mm and non‐BCSP status were independent risk factors for primary SR [OR 2.51 (95% CI 1.08–5.82), P = 0.03]. Conclusion: ER is safe and feasible for treating significant colorectal polyps. Robust accreditation within the BCSP has led to improvements in management, with lower rates of SR compared with non‐BCSP patients. Standardization, training in polyp assessment and treatment within a multidisciplinary team may help to select appropriate treatment strategies and improve outcomes. [ABSTRACT FROM AUTHOR]

Linked article: V. Schwierzeck, in screening programmes. J Eur Acad Dermatol Venereol 2020; 34: e225–e226. https://doi.org/10.1111/jdv.16196. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Ovarian metastases from gastrointestinal tract malignancies have been considered an ominous finding with poor prognosis. The aim of this project was to determine the impact on survival, and potential cure, when cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are combined to treat peritoneal malignancy in women with Krukenberg tumours. Method: A retrospective analysis of prospectively collected data between January 2010 and July 2015. Female patients undergoing complete CRS (macroscopic tumour removal) and HIPEC for pseudomyxoma peritonei (PMP) of appendiceal origin, or colorectal peritoneal metastases (CPM) were included. Survival was estimated using the Kaplan–Meier method and survival rates compared using the log‐rank test. Results: In total, 889 patients underwent surgery for peritoneal malignancy, of whom 551 were female. Of these, 504/551 (91%) underwent complete CRS and HIPEC. Overall, 405/504 (80%) had at least one involved ovary removed either during CRS and HIPEC or at their index prereferral operation. Three hundred and fifty‐two patients (87%) had an appendiceal tumour and 53 (13%) had CPM. At a median follow up of 40 months, overall survival (OS) did not differ significantly between patients with or without ovarian involvement in women with a primary low‐grade appendiceal tumour or CPM. In women with high‐grade primary appendiceal pathology, OS was significantly lower in patients with ovarian metastases compared with those without ovarian involvement. Conclusion: Women with ovarian metastases from low‐grade appendiceal tumours or colorectal cancer treated with CRS and HIPEC have similar survival rates to patients without ovarian metastases. Long‐term survival and cure is feasible in patients amenable to complete tumour removal. [ABSTRACT FROM AUTHOR]

Abstract: Preoperative radiotherapy continues to be widely used in patients with operable rectal cancer. However, the indications and goals for such treatment are evolving. Professor Marijnen reviews the historic and current evidence base for the use of preoperative neoadjuvant radiotherapy and the future challenges in tailoring the therapy according to the patients’ needs and tumour stage. [ABSTRACT FROM AUTHOR]

Stochastic Geometry Methods for Modeling Automotive Radar Interference [ABSTRACT FROM PUBLISHER]

Aim The Low Rectal Cancer Development programme (LOREC) perineal wound healing registry was developed to record data on abdominoperineal excision (APE) for rectal cancer in colorectal units in England between 2012 and 2014, to understand current practice in operative technique and results. Method Surgeons wishing to participate received secure Web-based access to the registry. Data were collected on preoperative staging, neoadjuvant treatment, operative details, histopathology, early outcome and follow up at 12 months. Results Forty-two units entered 266 patients. Of these, 172 (65%) patients underwent extralevator APE (ELAPE) and 94 had non-ELAPE procedures. On preoperative staging, 64% were mrT3/4, and 67% received neoadjuvant treatment. For the ELAPE group the perineal wound was closed primarily with mesh in 55% of patients, without mesh in 15% and with a flap in 21%. For non-ELAPE procedures, 54% of wounds were closed primarily without mesh, 29% primarily with mesh and 5% by a flap. Wound breakdown occurred in 30% and 31% of patients in the ELAPE and non-ELAPE groups, respectively, and was more common after neoadjuvant radiotherapy. Donor-site complications occurred in 17% of patients treated with a flap. Perineal morbidity was recorded in 11% of patients at 12 months. On histopathology, the resection margin was positive in 13% of patients in the ELAPE group and in 4% of patients in the non-ELAPE group. Conclusion The LOREC registry provides a picture of current APE practice in England. ELAPE was used in two-thirds of patients but does not appear to confer any additional morbidity. Primary closure with mesh appeared as effective as flap reconstruction. The prevalence of an involved resection margin was lower than reported in many historical series but still remains high in the ELAPE group. [ABSTRACT FROM AUTHOR]

In rectal cancer patients, the stage of the disease, local spread and distant metastases status drive the treatment decisions to be made. Histopathology remains the gold standard, but preoperative staging, particularly magnetic resonance imaging (MRI), is pivotal for defining surgical planes and finding patients who could potentially benefit from preoperative regimes. Unfortunately, due to a lack of awareness, expertise and practise the quality of rectal cancer MRI and histopathology reporting varies among centres. This paper highlights the most important and frequently occurring radiological and histopathological discrepancies/mistakes to be aware of. [ABSTRACT FROM AUTHOR]

The reduction of the incidence, detection and treatment of anastomotic leakage (AL) continues to challenge the colorectal surgical community. AL is not consistently defined and reported in clinical studies, its occurrence is variably reported and its impact on longterm morbidity and health-care resources has received relatively little attention. Controversy continues regarding the best strategies to reduce the risk. Diagnostic tests lack sensitivity and specificity, resulting in delayed diagnosis and increased morbidity. Intra-operative fluorescence angiography has recently been introduced as a means of real-time assessment of anastomotic perfusion and preliminary evidence suggests that it may reduce the rate of AL. In addition, concepts are emerging about the role of the rectal mucosal microbiome in AL and the possible role of new prophylactic therapies. In January 2016 a meeting of expert colorectal surgeons and pathologists was held in London, UK, to identify the ongoing controversies surrounding AL in colorectal surgery. The outcome of the meeting is presented in the form of research challenges that need to be addressed. [ABSTRACT FROM AUTHOR]

What is a "mucocele" of the appendix and how are these lesions best managed? We believe that "true mucoceles" are uncommon and that the majority of "mucoceles" visualized on imaging are secondary to mucinous appendiceal neoplasms. We propose that all "mucoceles" of the appendix should be considered as potentially harbouring a mucinous appendiceal neoplasm. [Extracted from the article]

The article focuses on the treatment options available for bowel cancer screening programmes (BCSP) and significant polyps and early colorectal cancer (SPECC). It talks about the use of colonoscopy, endoscopic resection and surgical excision for the treatment and management of the cancer. It tells about the use of biopsy to determine the nature of the lesion int he body.

The article focuses on the problems surrounding the significant polyp and early colorectal cancer (SPECC) for the rectum and colon for clinical management. It talks about the SPECC being used to understand the anatomical site of the lesion. It tells about SPECC being used to determine the nature of the lesion.

Objective: To describe the shared care and outcomes of patients with periocular skin tumours who underwent Mohs micrographic surgery (MMS) performed by dermatologists, followed by oculoplastic reconstruction undertaken by ophthalmologists at two teaching and one private hospital in Ireland. Research design and methods: This was a retrospective chart review at the Royal Victoria Eye and Ear Hospital, St James Hospital and the Hermitage Clinic. Results: One hundred and twenty seven patients had periocular Mohs surgery between November 2006 and January 2013 mainly indicated for basal cell carcinoma. The mean follow-up time was 2 years and to date there have been no local recurrences. Conclusions: MMS is available in Ireland and should be considered for patients with facial tumours in the ocular region. [ABSTRACT FROM AUTHOR]

SUMMARY Background and aims The treatment of peritoneal malignancies with cytoreductive surgery ( CRS) combined with hyperthermic intraperitoneal chemotherapy ( HIPEC) has been shown to be associated with massive surgical blood loss. Maintaining high fibrinogen levels throughout surgery may reduce blood loss in these patients. The primary aim of the study was to see if Tranexamic Acid (TXA) and cryoprecipitate reduced surgical blood loss and hence red cell transfusions. A comparison was made with a cohort of patients treated with fresh frozen plasma ( FFP) alone. The secondary aim was to measure the effect of both protocols on coagulation parameters and the incidence of arterial or venous thrombosis. Method We used prospectively collected data from 201 patients who had complete CRS with HIPEC for peritoneal malignancy using different protocols during two discrete 12-month time periods. Results The new transfusion protocol led to a higher average fibrinogen level intra-operatively and post-operatively, with a significant reduction in average RBC, FFP and platelet transfusion intra-operatively per patient from 4·2 to 1·8 units, 6·2 to 0·2 units and 0·1 to 0 units, respectively. No significant difference in PT or APTT was seen between patients treated with the standard and new protocols. Venous thrombosis occurred in seven patients treated with the standard protocol and five with the new protocol. A single case of arterial thrombosis was seen in both groups. Conclusion Patients treated with upfront TXA and cryoprecipitate during CRS required less RBC transfusion than those treated with the standard protocol of early FFP. [ABSTRACT FROM AUTHOR]

Abstract: As part of an approach to improve tumour regression and increase the proportion of patients with complete clinical and radiological response, Dr Perez reviews the methods and evidence base for augmenting therapy and thus augmenting response rates preoperatively. Much of the data reviewed were in the context of patients undergoing a watch‐and‐wait approach for rectal cancer after initial treatment with chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Background: In locally advanced rectal cancer (LARC) preoperative chemoradiation (CRT) is the standard of care, but the risk of local recurrence is low with good quality total mesorectal excision (TME), although many still develop metastatic disease. Current challenges in treating rectal cancer include the development of effective organ-preserving approaches and the prevention of subsequent metastatic disease. Neoadjuvant systemic chemotherapy (NACT) alone may reduce local and systemic recurrences, and may be more effective than postoperative treatments which often have poor compliance. Investigation of intensified NACT is warranted to improve outcomes for patients with LARC. The objective is to evaluate feasibility and efficacy of a four-drug regimen containing bevacizumab prior to surgical resection.Methods/design: This is a multi-centre, randomized phase II trial. Eligible patients must have histologically confirmed LARC with distal part of the tumour 4-12 cm from anal verge, no metastases, and poor prognostic features on pelvic MRI. Sixty patients will be randomly assigned in a 1:1 ratio to receive folinic acid + flurourcil + oxaliplatin (FOLFOX) + bevacizumab (BVZ) or FOLFOX + irinotecan (FOLFOXIRI) + BVZ, given in 2 weekly cycles for up to 6 cycles prior to TME. Patients stop treatment if they fail to respond after 3 cycles (defined as ≥ 30 % decrease in Standardised Uptake Value (SUV) compared to baseline PET/CT). The primary endpoint is pathological complete response rate. Secondary endpoints include objective response rate, MRI tumour regression grade, involved circumferential resection margin rate, T and N stage downstaging, progression-free survival, disease-free survival, overall survival, local control, 1-year colostomy rate, acute toxicity, compliance to chemotherapy.Discussion: In LARC, a neoadjuvant chemotherapy regimen - if feasible, effective and tolerable would be suitable for testing as the novel arm against the current standards of short course preoperative radiotherapy (SCPRT) and/or fluorouracil (5FU)-based CRT in a future randomised phase III trial.Trial Registration: Clinical trial identifier BACCHUS: NCT01650428. [ABSTRACT FROM AUTHOR]

Aim Many patients having anterior resection for rectal cancer suffer from severe long-term bowel dysfunction, known as low anterior resection syndrome ( LARS). The LARS score was developed in Denmark, and Swedish, Spanish and German versions have been validated. The aim of this study was to validate the English translation of the LARS score in British rectal cancer patients. Method Rectal cancer patients who underwent an anterior resection in 12 UK centres received the LARS score questionnaire, the EORTC QLQ-C30 and a single ad hoc quality of life question. A subgroup of patients received the LARS score questionnaire twice. Results The response rate was 80% and 451 patients were included in the analyses. A strong association between LARS score and quality of life (convergent validity) was found ( P < 0.01), discriminative validity was good ( P < 0.02) and the test-retest reliability was high (intraclass correlation coefficient 0.83). Conclusion The English translation of the LARS score has shown good psychometric properties comparable with recently published results from an international multicentre study. Thus, the English translation of the LARS score can be considered a valid and reliable tool for measuring LARS. [ABSTRACT FROM AUTHOR]

Aim The study determined the outcome of 1200 consecutive patients treated for peritoneal malignancy in one surgical unit over a 20-year period. Method A retrospective analysis was conducted of a custom designed prospective database of patients undergoing surgery for peritoneal malignancy since 1994. Patient demographics, tumour type, extent of surgery and outcome were recorded. Results Between 1994 and January 2014 (when the 1200th case had undergone surgery) 2956 patients were referred with a diagnosis of peritoneal malignancy. Pseudomyxoma peritonei of appendiceal origin was the pathology in 956/1200 (79.7%) patients. Other aetiologies included colorectal peritoneal metastases [89/1200 (7.4%)], abdominal mesothelioma [65/1200 (5.4%)] and miscellaneous [90/1200 (7.5%)]. Overall 863/1200 (71.9%) had complete cytoreduction, 294 (24.5%) had maximal tumour debulking and 43 (3.6%) had laparotomy only. The proportion undergoing complete cytoreduction per quartile of 300 patients was 60.7%, 65.0%, 77.0% and 80.3%. Laparotomy and biopsy fell from 6.4% in the first quartile to 2.7%, 1.7% and 1.3% in subsequent quartiles. The 30-day mortality in the four quartiles was 3.0%, 1.0%, 0.7% and 0.7%. The 5-year survival was 84% in the 636 patients with appendix tumours who had complete cytoreduction, 76% in the 38 with abdominal mesothelioma and 44% in the 60 with colorectal peritoneal metastases. Conclusion A centralized approach facilitated high volume experience in a single centre with an increase in the completeness of surgical excision rates and a reduction in mortality and morbidity over time. [ABSTRACT FROM AUTHOR]

Aim Elevation of the preoperative tumour markers in pseudomyxoma peritonei (PMP) is common and is a risk factor for recurrence. There has, however, been no documentation of the effect of complete tumour removal on tumour markers levels after cytoreductive surgery ( CRS) and hyperthermic intraperitoneal chemotherapy ( HIPEC). The aim of the study was to compare the tumour markers 7 days after surgery in patients with elevated preoperative levels. Method This was an observational prospective study of patients with PMP of appendiceal origin treated in one of the UK National Referral Centres for this condition. Thirty patients [median age = 61 (range: 31-74) years; six men] with an elevated preoperative level of carcinoembryonic antigen ( CEA), carbohydrate antigen 125 ( CA-125) and/or carbohydrate antigen 19-9 ( CA19-9) underwent repeated estimation, 7 days after CRS and HIPEC for PMP. Results The median preoperative CEA level of 12 μg/l fell to 0.75 μg/l postoperatively ( P < 0.0001), CA-125 fell from 45 to 31 kU/l ( P = 0.183) and CA19-9 fell from 134 to 37 kU/l ( P = 0.003). The CEA was raised in 22 (73%) of 30 patients preoperatively and in two (7%) of 30 patients 7 days after surgery ( P < 0.0001). The corresponding data for CA-125 were 18 (60%) and 13 (43%) ( P = 0.196) and for CA19-9 they were 24 (80%) and 16 (53%) ( P = 0.028). Conclusion This is the first documentation of a reduction or normalization of CEA 7 days after CRS, but not for CA19-9 or CA-125. This may indicate completeness of surgical resection and could aid selection for adjuvant therapy and predict prognosis. Long-term follow-up is, however, necessary to determine the significance of this observation. [ABSTRACT FROM AUTHOR]

Background The learning curves for cytoreductive surgery with intraperitoneal chemotherapy for treatment of pseudomyxoma peritonei ( PMP) were explored between international centres/surgeons to identify institutional or other factors that might affect performance. Methods Data from patients with PMP treated with the combined procedure across 33 international centres between 1993 and 2012 were analysed retrospectively . A risk-adjusted sequential probability ratio test was conducted after defining the target outcome as early oncological failure (disease progression within 2 years of treatment), an acceptable risk for the target outcome (odds ratio) of 2, and type I/ II error rates of 5 per cent. The risk prediction model was elaborated and patients were evaluated sequentially for each centre/surgeon. The learning curve was considered to be overcome and proficiency achieved when the odds ratio for early oncological failure became smaller than 2. Results Rates of optimal cytoreduction, severe postoperative morbidity and early oncological failure were 84·4, 25·7 and 29·0 per cent respectively. The median annual centre volume was 17 (range 6-66) peritoneal malignancies. Only eight of the 33 centres and six of 47 surgeons achieved proficiency after a median of 100 (range 78-284) and 96 (86-284) procedures respectively. The most important institutional factor affecting surgical performance was centre volume. Conclusion The learning curve is extremely long, so centralization and/or networking of centres is necessary to assure quality of services. One centre for every 10-15 million inhabitants would be ideal. [ABSTRACT FROM AUTHOR]