Spectral imaging enables contrast agent-free real-time ischemia monitoring in laparoscopic surgery.

Laparoscopic surgery has evolved as a key technique for cancer diagnosis and therapy. While characterization of the tissue perfusion is crucial in various procedures, such as partial nephrectomy, doing so by means of visual inspection remains highly challenging. We developed a laparoscopic real-time multispectral imaging system featuring a compact and lightweight multispectral camera and the possibility to complement the conventional surgical view of the patient with functional information at a video rate of 25 Hz. To enable contrast agent-free ischemia monitoring during laparoscopic partial nephrectomy, we phrase the problem of ischemia detection as an out-of-distribution detection problem that does not rely on data from any other patient and uses an ensemble of invertible neural networks at its core. An in-human trial demonstrates the feasibility of our approach and highlights the potential of spectral imaging combined with advanced deep learning-based analysis tools for fast, efficient, reliable, and safe functional laparoscopic imaging.

Lessons learned after one year of COVID-19 from a urologist and radiotherapist view: A German survey on prostate cancer diagnosis and treatment.

INTRODUCTION: Since the beginning of the pandemic in 2020, COVID-19 has changed the medical landscape. International recommendations for localized prostate cancer (PCa) include deferred treatment and adjusted therapeutic routines. MATERIALS AND METHODS: To longitudinally evaluate changes in PCa treatment strategies in urological and radiotherapy departments in Germany, a link to a survey was sent to 134 institutions covering two representative baseline weeks prior to the pandemic and 13 weeks from March 2020 to February 2021. The questionnaire captured the numbers of radical prostatectomies, prostate biopsies and case numbers for conventional and hypofractionation radiotherapy. The results were evaluated using descriptive analyses. RESULTS: A total of 35% of the questionnaires were completed. PCa therapy increased by 6% in 2020 compared to 2019. At baseline, a total of 69 radiotherapy series and 164 radical prostatectomies (RPs) were documented. The decrease to 60% during the first wave of COVID-19 particularly affected low-risk PCa. The recovery throughout the summer months was followed by a renewed reduction to 58% at the end of 2020. After a gradual decline to 61% until July 2020, the number of prostate biopsies remained stable (89% to 98%) during the second wave. The use of RP fluctuated after an initial decrease without apparent prioritization of risk groups. Conventional fractionation was used in 66% of patients, followed by moderate hypofractionation (30%) and ultrahypofractionation (4%). One limitation was a potential selection bias of the selected weeks and the low response rate. CONCLUSION: While the diagnosis and therapy of PCa were affected in both waves of the pandemic, the interim increase between the peaks led to a higher total number of patients in 2020 than in 2019. Recommendations regarding prioritization and fractionation routines were implemented heterogeneously, leaving unexplored potential for future pandemic challenges.

To defer or not to defer? A German longitudinal multicentric assessment of clinical practice in urology during the COVID-19 pandemic.

INTRODUCTION: After the outbreak of COVID-19 unprecedented changes in the healthcare systems worldwide were necessary resulting in a reduction of urological capacities with postponements of consultations and surgeries. MATERIAL AND METHODS: An email was sent to 66 urological hospitals with focus on robotic surgery (RS) including a link to a questionnaire (e.g. bed/staff capacity, surgical caseload, protection measures during RS) that covered three time points: a representative baseline week prior to COVID-19, the week of March 16th-22nd and April 20th-26th 2020. The results were evaluated using descriptive analyses. RESULTS: 27 out of 66 questionnaires were analyzed (response rate: 41%). We found a decrease of 11% in hospital beds and 25% in OR capacity with equal reductions for endourological, open and robotic procedures. Primary surgical treatment of urolithiasis and benign prostate syndrome (BPS) but also of testicular and penile cancer dropped by at least 50% while the decrease of surgeries for prostate, renal and urothelial cancer (TUR-B and cystectomies) ranged from 15 to 37%. The use of personal protection equipment (PPE), screening of staff and patients and protection during RS was unevenly distributed in the different centers-however, the number of COVID-19 patients and urologists did not reach double digits. CONCLUSION: The German urological landscape has changed since the outbreak of COVID-19 with a significant shift of high priority surgeries but also continuation of elective surgical treatments. While screening and staff protection is employed heterogeneously, the number of infected German urologists stays low.

Light source calibration for multispectral imaging in surgery.

PURPOSE: Live intra-operative functional imaging has multiple potential clinical applications, such as localization of ischemia, assessment of organ transplantation success and perfusion monitoring. Recent research has shown that live monitoring of functional tissue properties, such as tissue oxygenation and blood volume fraction, is possible using multispectral imaging in laparoscopic surgery. While the illuminant spectrum is typically kept constant in laparoscopic surgery and can thus be estimated from preoperative calibration images, a key challenge in open surgery originates from the dynamic changes of lighting conditions. METHODS: The present paper addresses this challenge with a novel approach to light source calibration based on specular highlight analysis. It involves the acquisition of low-exposure time images serving as a basis for recovering the illuminant spectrum from pixels that contain a dominant specular reflectance component. RESULTS: Comprehensive in silico and in vivo experiments with a range of different light sources demonstrate that our approach enables an accurate and robust recovery of the illuminant spectrum in the field of view of the camera, which results in reduced errors with respect to the estimation of functional tissue properties. Our approach further outperforms state-of-the-art methods proposed in the field of computer vision. CONCLUSION: Our results suggest that low-exposure multispectral images are well suited for light source calibration via specular highlight analysis. This work thus provides an important first step toward live functional imaging in open surgery.

IgG4-Associated Adrenalitis-a Case Report.

A 67-year-old man was adrenalectomized due to a tumor measuring 100 mm. Specimens revealed an inflammation with slight fibrosis and moderate infiltrates of lymphocytes and plasmacytes with immunoreactivity for IgG and IgG4 resulting in the diagnosis of an active IgG4-associated adrenalitis. To our knowledge, this is the first reported active adrenalitis of this type. It should be the precursor lesion of the adrenal calcifying fibrous tumor that was reported once before.

Gut Microbial Transformation of the Dietary Imidazoquinoxaline Mutagen MelQx Reduces Its Cytotoxic and Mutagenic Potency.

The diverse community of microbes present in the human gut has emerged as an important factor for cancer risk, potentially by altering exposure to chemical carcinogens. In the present study, human gut bacteria were tested for their capacity to transform the carcinogenic heterocyclic amine 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx). Eubacterium hallii, Lactobacillus reuteri, and Lactobacillus rossiae were able to convert MelQx to a new microbial metabolite characterized on the basis of high-resolution mass spectrometry and NMR as 9-hydroxyl-2,7-dimethyl-7,9,10,11-tetrahydropyrimido[2',1':2,3]imidazo[4,5-f]quinoxaline (MelQx-M1), resulting from conjugation with activated glycerol. Acrolein derived from the decomposition of 3-hydroxypropionaldehyde, which is the product of bacterial glycerol/diol dehydratase activity, was identified as the active compound responsible for the formation of MelQx-M1. A complex human gut microbial community obtained from invitro continuous intestinal fermentation was found to also transform MelQx to MelQx-M1. MelQx-M1 had slightly reduced cytotoxic potency toward human colon epithelial cells invitro, and diminished mutagenic potential toward bacteria after metabolic activation. As bacterially derived acrolein also transformed 2 other HCAs, namely 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2-amino-3-methylimidazo[4,5-f]quinoline, these results generalize the capacity of gut microbiota to detoxify HCAs in the gut, potentially modulating cancer risk.

The strict anaerobic gut microbe Eubacterium hallii transforms the carcinogenic dietary heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).

2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) is the most abundant food-derived heterocyclic aromatic amine in well-cooked meats and may contribute to the recognized carcinogenicity of processed meats. In this study, a panel of human gut microbes was tested for their ability to convert PhIP to a conjugate PhIP-M1. Eubacterium hallii was newly identified to catalyse the conversion of PhIP to PhIP-M1 with high efficiency. The reaction was shown to involve the metabolism of glycerol to 3-hydroxypropionaldehyde as a key pathway. The proficiency of E. hallii in transforming PhIP in the presence of a complex intestinal microbiota was confirmed using batch fermentations inoculated with effluents from a continuous intestinal fermentation model mimicking human proximal and distal colon microbiota. In batch fermentations inoculated with proximal colon microbiota, PhIP-M1 transformation corresponded to an up to 300-fold increase of E. hallii. In contrast, PhIP transformation of distal colon microbiota was low but increased by 120-fold after supplementation with E. hallii. These findings indicate for the first time the relevance of the abundant commensal strict anaerobe E. hallii in the transformation of a dietary carcinogen that could contribute to its detoxification in the human colon.

Mechanisms of dexamethasone-mediated inhibition of cAMP-induced tPA expression in rat mesangial cells.

BACKGROUND: Glucocorticoids are efficiently used as antiinflammatory and immunosuppressive therapies of renal diseases. However, long-term treatment often is associated with net changes in the turnover of extracellular matrix (ECM) components. METHODS: We examined the impact of glucocorticoids on cAMP-triggered expression of tissue plasminogen activator (tPA), a protease prominently involved in glomerular ECM turnover. RESULTS: By ELISA, the db-cAMP-mediated increase in extracellular tPA activity secreted by mesangial cells (MC) was markedly reduced in the presence of 100 nmol/L dexamethasone. The decrease of enzymatic activity was accompanied by an attenuation of tPA expression, as shown by Northern blot analysis. Furthermore, dexamethasone increased the steady-state mRNA level of the tPA-inhibitor 1 (PAI-1), thereby providing an additional mode of regulation of tPA activity. Mutational analysis revealed that the inhibition of tPA expression was localized within the proximal 2.3 kb of the 5'-flanking region of the rat tPA gene and critically depended on a cAMP response element (CRE) at position -185. EMSA demonstrated that binding to this CRE was affected by dexamethasone, since the db-cAMP-caused DNA binding of CREB and C/EBPbeta-immunopositive complexes was substantially reduced by dexamethasone. In parallel, dexamethasone decreased the nuclear abundance of db-cAMP-induced C/EBPbeta and phosphorylated CREB protein without affecting the total level of either transcription factor. CONCLUSIONS: Suppression of cAMP-stimulated tPA expression by glucocorticoids occurs by interference with CREB and C/EBPbeta, the major transcription factors mediating cAMP responses. These observations may provide the molecular basis for the sclerotic processes within the glomerulus often complicating chronic glucocorticoid treatment.

Glucocorticoid-mediated suppression of cytokine-induced matrix metalloproteinase-9 expression in rat mesangial cells: involvement of nuclear factor-kappaB and Ets transcription factors.

Glucocorticoids and their synthetic analogs exert potent antiinflammatory actions that, in most cases, are due to an inhibition of the expression of inflammatory genes. In this study, we elucidated the mechanisms of dexamethasone-mediated suppression of matrix metalloproteinase-9 (MMP-9) expression triggered by IL-1beta in rat mesangial cells. Treatment of mesangial cells with dexamethasone markedly reduced the gelatinolytic content of conditioned media due to a decrease in MMP-9 expression. Cloning of a 1.3-kb fragment of the rat MMP-9 gene promoter and subsequent site- directed mutagenesis revealed that a nuclear factor kappaB (NF-kappaB) site at -561 to -550 and a region from -511 to -497 bearing a distal activator protein 1 site adjacent to an Ets-binding site are essentially involved in the IL-1beta-mediated transactivation of MMP-9. Inhibition of MMP-9 expression by dexamethasone resides in a promoter region downstream of -597. The IL-1beta-caused increase in DNA binding of both NF-kappaB and Ets-1 immunopositive complexes was substantially suppressed by dexamethasone as shown by EMSA. This was paralleled with a reduced abundance of p65 and Ets-1 proteins in cell nuclei concomitantly with a reduced inhibitor of kappaB (IkappaB) degradation. In addition to NF-kappaB, we suggest a pivotal role for the Ets binding site, in concert with a distal activator protein-1 element, in the transcriptional suppression of cytokine-induced MMP-9 expression by glucocorticoids.