Basal cell carcinoma trends in Thailand: a 10-year retrospective study of demographic, clinical and histopathological features

Background: Basal cell carcinoma (BCC) is the most common skin cancer with globally increasing incidence. To date, the information regarding BCC in Thailand is limited.Objective: To evaluate the demographic, clinical, histopathological trends of BCC and other contributing factors.Methods: We retrospectively reviewed the demographic, clinical and histological data of all BCC outpatients from January 2009 to December 2018.Results: From 278 BCC patients recruited to this study, most of them (71.6%) were older than 60 years old. The most common histological subtype was nodular BCC (63.3%). A statistically significant association was observed between histological variant and location of the tumor; H and M area were associated with nodular BCC, L area was related to superficial subtype (p-value < 0.001). Misdiagnosis of BCC was observed in 53 cases, mostly as melanocytic nevus (30.2%), and about quarter (26.4%) was made by board-certified dermatologists.Conclusions: Nodular BCC is significantly associated with H and M area, while superficial subtype is related to L location. Quarter of the patients already have large tumors at their first presentation. Misdiagnosis of BCC is not uncommon.

Diversity of microglial transcriptional responses during opioid exposure and neuropathic pain

Microglia take on an altered morphology during chronic opioid treatment. This morphological change is broadly used to identify the activated microglial state associated with opioid side effects, including tolerance and opioid-induced hyperalgesia (OIH). Following chronic opioid treatment and peripheral nerve injury (PNI) microglia in the spinal cord display similar morphological responses. Consistent with this observation, functional studies have suggested that microglia activated by PNI or opioids engage common molecular mechanisms to induce hypersensitivity. Here we conducted deep RNA sequencing of acutely isolated spinal cord microglia from male mice to comprehensively interrogate transcriptional states and mechanistic commonality between multiple OIH and PNI models. Following PNI, we identify a common early proliferative transcriptional event across models that precedes the upregulation of histological markers of activation, followed by a delayed and injury-specific transcriptional response. Strikingly, we found no such transcriptional responses associated with opioid-induced microglial activation, consistent with histological data indicating that microglia number remain stable during morphine treatment. Collectively, these results reveal the diversity of pain-associated microglial transcriptomes and point towards the targeting of distinct insult-specific microglial responses to treat OIH, PNI, or other CNS pathologies.

Rubella Virus Infected Macrophages and Neutrophils Define Patterns of Granulomatous Inflammation in Inborn and Acquired Errors of Immunity

Rubella virus (RuV) has recently been found in association with granulomatous inflammation of the skin and several internal organs in patients with inborn errors of immunity (IEI). The cellular tropism and molecular mechanisms of RuV persistence and pathogenesis in select immunocompromised hosts are not clear. We provide clinical, immunological, virological, and histological data on a cohort of 28 patients with a broad spectrum of IEI and RuV-associated granulomas in skin and nine extracutaneous tissues to further delineate this relationship. Combined immunodeficiency was the most frequent diagnosis (67.8%) among patients. Patients with previously undocumented conditions, i.e., humoral immunodeficiencies, a secondary immunodeficiency, and a defect of innate immunity were identified as being susceptible to RuV-associated granulomas. Hematopoietic cell transplantation was the most successful treatment in this case series resulting in granuloma resolution; steroids, and TNF-α and IL-1R inhibitors were moderately effective. In addition to M2 macrophages, neutrophils were identified by immunohistochemical analysis as a novel cell type infected with RuV. Four patterns of RuV-associated granulomatous inflammation were classified based on the structural organization of granulomas and identity and location of cell types harboring RuV antigen. Identification of conditions that increase susceptibility to RuV-associated granulomas combined with structural characterization of the granulomas may lead to a better understanding of the pathogenesis of RuV-associated granulomas and discover new targets for therapeutic interventions.

Spectrum of interstitial lung diseases and their association with pulmonary hypertension

Interstitial lung diseases (ILDs) are an intriguing group of pulmonary disorders, which still require the study of epidemiological, genetic, pathophysiological, clinical, and radiological parameters. Pulmonary hypertension (PH) is an underreported complication in interstitial lung diseases which is associated with worse outcome. In our study, we have reported the spectrum of ILDs and estimated the prevalence of pulmonary hypertension among these subjects at a tertiary care centre. A cross-sectional study was performed in which demographical, clinical, radiological, and histological data of subjects with ILD, attending the department of Respiratory Medicine in the University was collected from 1st September 2018 to 31st August 2019. Serological tests were done wherever indicated. Standard criteria along with multidisciplinary opinion were needed to arrive at the final diagnosis. All subjects were screened for pulmonary hypertension via 2-D echocardiography. Mean pulmonary artery pressure ≥20 mmHg was used to define PH. In the defined period, 239 subjects were enrolled (58% females, n=141; mean age 52.38±13.40 years). A tissue diagnosis was obtained in 34% cases. The most common ILD was hypersensitivity pneumonitis (32.2%), followed by autoimmune-ILD (31.4%), idiopathic pulmonary fibrosis (IPF) (15.9%) and sarcoidosis (12.6%), non-IPF idiopathic interstitial pneumonitis (2.1%) and rest 21 (5.9%) subjects were diagnosed as other types of ILD. Pulmonary hypertension was seen in 46.0% of subjects.

Automatic Evaluation of Histological Prognostic Factors Using Two Consecutive Convolutional Neural Networks on Kidney Samples

Background and Objectives: The prognosis of patients undergoing kidney tumor resection or kidney donation is linked to many histological criteria. These criteria notably include glomerular density, glomerular volume, vascular luminal stenosis, and severity of interstitial fibrosis/tubular atrophy. Automated measurements through a Deep Learning approach could save time and provide more precise data. This work aimed to develop a free tool to automatically obtain kidney histological prognostic features. Design, setting, participants, and measurements: Two hundred and forty one samples of healthy kidney tissue were split into 3 independent cohorts. The "Training" cohort (n=65) was used to train two Convolutional Neural Networks: one to detect the cortex and a second one to segment the kidney structures. The "Test" cohort (n=50) assessed their performances by comparing manually outlined regions of interest to predicted ones. The "Application" cohort (n=126) compared prognostic histological data obtained manually or through the algorithm based on the combination of the two Convolutional Neural Networks. Results: In the Test cohort, the networks isolated the cortex and segmented the elements of interest with good performances (more than 90% of the cortex, healthy tubules, glomeruli, and even globally sclerotic glomeruli were detected). In the Application cohort, the expected and predicted prognostic data were significantly correlated. The correlation coefficients r were respectively 0.85 for glomerular volume, 0.51 for glomerular density, 0.75 for interstitial fibrosis, 0.71 for tubular atrophy, and 0.73 for vascular intimal thickness. The algorithm had a good ability to predict significant (> 25%) tubular atrophy and interstitial fibrosis level (ROC curve with an area under the curve 0.92 and 0.91, respectively) or a significant vascular luminal stenosis (> 50%) (area under the curve 0.85). Conclusion: This freely available tool enables the automated segmentation of kidney tissue to obtain prognostic histological data in a fast, objective, reliable and reproducible way.

P-BN20 An evaluation of the accuracy of sonography for the measurements of gallbladder polyps across 3 UK hospital trusts: should the surveillance guidelines be revised?

Background Transabdominal ultrasound scan (USS) is recommended for surveillance of gallbladder polyps (GBP), this is to stratify risk for premalignant potential. European Society of Gastrointestinal and Abdominal Radiology make recommendations based on increases of as small 2mm during sequential USS surveillance. Our aim is to determine the accuracy of USS in diagnosis and measurement of GBP. Methods Measurement data for all GBPs were gathered for three hospital trusts across a 12 year period and retrospectively reviewed. USS findings (diagnosis of GBP and GBP size) were compared with histological diagnosis and measurements, when both reports were available, in those patients who had underwent cholecystectomy at the time of data collection. Results For the first two hospital trusts, 778 USS were reviewed which identified patients with GBP. 78 patients had undergone cholecystectomy at time of data collection. Only 17/78 of patients had histological evidence of GBP. Of those without GBP, 37/61 had gallstones. For the third hospital trust, 41 GBP histological reports were identified, 20 could be directly compared with USS. Collectively 29 USS reports were directly compared with GBP histology reports. Only, 31% had results which were in agreement to within 1mm. The mean measurement discrepancy between both modalities was 5.41mm. Conclusions USS does not provide an accurate diagnosis of GBP, it is likely that USS misdiagnoses gallstones as GBP. Moreover, when comparing USS measurements with histological data, there is 31% accuracy of measurement to within 1mm in this cohort. Current guidelines recommend cholecystectomy if there is an interval change of 2mm or more; this data shows a measurement error of more than this.

Blue Cod, Parapercis Colias, Maturity, Fecundity, Sex Change, and Potential Drivers of Sex Ratio in The Marlborough Sounds

<p>Blue cod, Parapercis colias (Pinguipedidae), are widely considered to be the most important recreational finfish species in the South Island. However, blue cod have been declining in abundance in the Marlborough Sounds for many years, and currently, sex ratios are highly male- biased. Blue cod are believed to be a socially structured hermaphroditic species whose populations are prone to local depletion. A potting survey in the Marlborough Sounds was carried out by NIWA in 2013, and along with environmental measurements, 3247 blue cod were measured, weighed, sexed, and stage of sexual maturity was classified macroscopically at sea. Gonads from a subsample of these fish were removed and preserved. In Chapter Two, the preserved gonads were processed histologically and a species-specific histological maturity key was developed. Histological and macroscopic maturity classifications and length-at-maturity estimates were compared. Additionally, estimates of spawning frequency and batch fecundity were made using histological and gravimetric methods. In Chapter Three, possible drivers of sex ratio were investigated using the survey data. Density, large male influence, and environmental factors were considered. In Chapter Four, the feasibility of using digital imaging software to age blue cod otoliths was investigated using the OtolithM application in ImagePro Premier. There was poor agreement between macroscopic and histological maturity classifications (20%, overall). Macroscopic methods overestimated the proportion of mature fish at length in the larger sample, which led to biased length-at-50% maturity (L₅₀) estimates. Macroscopic L₅₀ estimates differed markedly from histology estimates. Using histological data, male L₅₀ was 26 cm TL. Histology indicated that there was no length at which 100% of females were mature. Therefore, a three-parameter capped logistic model was used. Histologically, female L₅₀ was 23.6 cm TL, and the Cap was 0.78, indicating the proportion of mature females reached an asymptote at 0.78. Spawning frequency was 4.6 days, and mean relative batch fecundity was 6.5 hydrated oocytes per gram body weight (SD = 3.3). Hermaphroditism was confirmed for blue cod and was macroscopically identifiable. The analyses in Chapter Three indicated that density had some effect on sex ratio, and large males influenced local sex ratios. Finally, the imaging software could not accurately estimate age compared to an expert reader, and it produced highly variable age estimates. This research found that the macroscopic maturity classifications for blue cod were inaccurate, and revision of the macroscopic key is suggested. The biased estimates of L₅₀ from macroscopic data could lead to biased estimates of spawning stock biomass (SSB). Batch fecundity was markedly lower than the previously reported estimates. The finding of a macroscopically identifiable hermaphroditic stage suggested that ‘hermaphrodite’ should be added as a sex class in the macroscopic key. From the GLM in Chapter Three, in more dense populations, the proportion of males increased. This may have been from changes to male mating strategies, or density may influence the occurrence of primary and secondary males. Finally, areas with males > 45 cm TL had a higher proportion of females, suggesting that large males should be protected in order to help balance sex ratios.</p>

Blue Cod, Parapercis Colias, Maturity, Fecundity, Sex Change, and Potential Drivers of Sex Ratio in The Marlborough Sounds

<p>Blue cod, Parapercis colias (Pinguipedidae), are widely considered to be the most important recreational finfish species in the South Island. However, blue cod have been declining in abundance in the Marlborough Sounds for many years, and currently, sex ratios are highly male- biased. Blue cod are believed to be a socially structured hermaphroditic species whose populations are prone to local depletion. A potting survey in the Marlborough Sounds was carried out by NIWA in 2013, and along with environmental measurements, 3247 blue cod were measured, weighed, sexed, and stage of sexual maturity was classified macroscopically at sea. Gonads from a subsample of these fish were removed and preserved. In Chapter Two, the preserved gonads were processed histologically and a species-specific histological maturity key was developed. Histological and macroscopic maturity classifications and length-at-maturity estimates were compared. Additionally, estimates of spawning frequency and batch fecundity were made using histological and gravimetric methods. In Chapter Three, possible drivers of sex ratio were investigated using the survey data. Density, large male influence, and environmental factors were considered. In Chapter Four, the feasibility of using digital imaging software to age blue cod otoliths was investigated using the OtolithM application in ImagePro Premier. There was poor agreement between macroscopic and histological maturity classifications (20%, overall). Macroscopic methods overestimated the proportion of mature fish at length in the larger sample, which led to biased length-at-50% maturity (L₅₀) estimates. Macroscopic L₅₀ estimates differed markedly from histology estimates. Using histological data, male L₅₀ was 26 cm TL. Histology indicated that there was no length at which 100% of females were mature. Therefore, a three-parameter capped logistic model was used. Histologically, female L₅₀ was 23.6 cm TL, and the Cap was 0.78, indicating the proportion of mature females reached an asymptote at 0.78. Spawning frequency was 4.6 days, and mean relative batch fecundity was 6.5 hydrated oocytes per gram body weight (SD = 3.3). Hermaphroditism was confirmed for blue cod and was macroscopically identifiable. The analyses in Chapter Three indicated that density had some effect on sex ratio, and large males influenced local sex ratios. Finally, the imaging software could not accurately estimate age compared to an expert reader, and it produced highly variable age estimates. This research found that the macroscopic maturity classifications for blue cod were inaccurate, and revision of the macroscopic key is suggested. The biased estimates of L₅₀ from macroscopic data could lead to biased estimates of spawning stock biomass (SSB). Batch fecundity was markedly lower than the previously reported estimates. The finding of a macroscopically identifiable hermaphroditic stage suggested that ‘hermaphrodite’ should be added as a sex class in the macroscopic key. From the GLM in Chapter Three, in more dense populations, the proportion of males increased. This may have been from changes to male mating strategies, or density may influence the occurrence of primary and secondary males. Finally, areas with males > 45 cm TL had a higher proportion of females, suggesting that large males should be protected in order to help balance sex ratios.</p>

Preliminary Results of an Ongoing Prospective Clinical Trial on the Use of 68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI in Staging of High-Risk Prostate Cancer Patients

The aim of the present study is to investigate the synergic role of 68Ga-PSMA PET/MRI and 68Ga-DOTA-RM2 PET/MRI in prostate cancer (PCa) staging. We present pilot data on twenty-two patients with biopsy-proven PCa that underwent 68Ga-PSMA PET/MRI for staging purposes, with 19/22 also undergoing 68Gaa-DOTA-RM2 PET/MRI. TNM classification based on image findings was performed and quantitative imaging parameters were collected for each scan. Furthermore, twelve patients underwent radical prostatectomy with the availability of histological data that were used as the gold standard to validate intraprostatic findings. A DICE score between regions of interest manually segmented on the primary tumour on 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and on T2 MRI was computed. All imaging modalities detected the primary PCa in 18/19 patients, with 68Ga-DOTA-RM2 PET not detecting any lesion in 1/19 patients. In the remaining patients, 68Ga-PSMA and MRI were concordant. Seven patients presented seminal vesicles involvement on MRI, with two of these being also detected by 68Ga-PSMA, and 68Ga-DOTA-RM2 PET being negative. Regarding extraprostatic disease, 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and MRI resulted positive in seven, four and five patients at lymph-nodal level, respectively, and at a bone level in three, zero and one patients, respectively. These preliminary results suggest the potential complementary role of 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and MRI in PCa characterization during the staging phase.

Clinical and histological evaluation of a dual sequential application of fractional 10,600 nm and 1570 nm lasers, compared to single applications in a porcine model

The sequential application of fractional ablative/10,600 nm/CO2 followed by 1570 nm non-ablative laser treatment might produce better results than applying either laser treatment alone. However, histological data regarding the safety of this combination is lacking. This study aimed to assess and compare clinical effects, histological tissue damage, and wound healing after monochromatic and sequential fractional laser treatments. In this prospective porcine model study, three adult female pigs were each irradiated using three different wavelengths: (a) monochromatic fractional ablative CO2 laser; (b) monochromatic fractional non-ablative 1570 nm laser; (c) sequential fractional 10,600 nm/CO2 followed by 1570 nm laser treatment. There were six power levels in the monochromatic 1570 nm laser, five in the 10,600 nm/CO2, and five in the sequential treatment. The immediate skin reaction (ISR), crusting and adverse effects, was evaluated across different time points throughout the healing process. Wound biopsies were taken at immediately after (0) and at 3, 7, and 14 days after irradiation. Depth and width of craters, and width of coagulation zone were measured and compared. Similar ISR and crusting score values were obtained following the monochromatic and sequential irradiation in a similar dose–response manner. During 14 days of follow-up, the skin looked intact and non-infected with no signs of necrosis. The mean depth and width of craters were comparable only at the maximal energy level (240 mJ) of CO2 laser, with the coagulation size greater after the sequential treatment. In histology, a similar wound healing was evident. On day 3, crusts were observed above all lesions as was epithelial regeneration. The sequential irradiation with 10,600 nm/CO2 and 1570 nm lasers did not pose any additional risk compared to the risk of each laser alone.