WITHDRAWN: The benefit of adopting Microultrasound in the prostate cancer imaging pathway : A lesion-by-lesion analysis

INTRODUCTION: Microultrasound (MicroUS) is a novel imaging modality relying on a high-frequency transducer which confers a three-fold improvement in spatial resolution as compared with conventional transrectal ultrasound. We evaluated the diagnostic value of MRI-MicroUS fusion biopsy and determined the additional benefit of employing MicroUS. METHODS: Retrospective analysis of consecutive treatment-naïve men undergoing MRI-MicroUS fusion biopsy between May 2018 and March 2019. Pre-biopsy MRI was systematically reviewed in a dedicated meeting where suspicious lesions PIRADS≥3 were registered and uploaded in the ExactVu MicroUS device. MRI and MicroUS lesions were individually marked in a PIRADS v2 scheme. The biopsy protocol included MRI-MicroUS fusion and MicroUS targeted biopsies; systematic biopsies were performed at clinician's discretion. The diagnostic value was evaluated in terms of detection rate of clinically significant prostate cancer, defined as Gleason pattern≥4 at histology. RESULTS: In all, 148 patients with a median age of 69 years (IQR 63-74) and median PSA density of 0.16ng/ml/cc (0.10-0.23) were included. Clinically significant cancer was detected in 42.5% (63/148) patients. MRI detected 89 lesions in the peripheral zone; 73% (65/89) were visible on MicroUS. Clinically significant cancer was detected in 46.1% (30/65) MRI and MicroUS visible lesions, and in 4.2% (1/24) lesions only visible on mpMRI. MicroUS additionally identified 35 suspicious lesions non-visible on MRI of which clinically significant cancer was present in 25.7% (9/35). CONCLUSION: Adding MicroUS to the conventional pathway seems to increase the detection rate of clinically significant disease in unselected men undergoing biopsy.

The benefit of adopting Microultrasound in the prostate cancer imaging pathway: A lesion-by-lesion analysis: Biopsies prostatiques guidée par micro-échographie, quel bénéfice ? Une analyse lésion par lésion.

INTRODUCTION: - Microultrasound (MicroUS) is a novel imaging modality relying on a high-frequency transducer which confers a three-fold improvement in spatial resolution as compared with conventional transrectal ultrasound. We evaluated the diagnostic value of MRI-MicroUS fusion biopsy and determined the additional benefit of employing MicroUS. METHODS: - Retrospective analysis of consecutive treatment-naïve men undergoing MRI-MicroUS fusion biopsy between May 2018 and March 2019. Pre-biopsy MRI was systematically reviewed in a dedicated meeting where suspicious lesions PIRADS ≥ 3 were registered and uploaded in the ExactVu MicroUS device. MRI and MicroUS lesions were individually marked in a PIRADS v2 scheme. The biopsy protocol included MRI-MicroUS fusion and MicroUS targeted biopsies; systematic biopsies were performed at clinician's discretion. The diagnostic value was evaluated in terms of detection rate of clinically significant prostate cancer, defined as Gleason pattern ≥ 4 at histology. RESULTS: - In all, 148 patients with a median age of 69 years (IQR 63-74) and median PSA density of 0.16 ng/ml/cc (0.10-0.23) were included. Clinically significant cancer was detected in 42.5% (63/148) patients. MRI detected 89 lesions in the peripheral zone; 73% (65/89) were visible on MicroUS. Clinically significant cancer was detected in 46.1% (30/65) MRI and MicroUS visible lesions, and in 4.2% (1/24) lesions only visible on mpMRI. MicroUS additionally identified 35 suspicious lesions non-visible on MRI of which clinically significant cancer was present in 25.7% (9/35). CONCLUSION: - Adding MicroUS to the conventional pathway seems to increase the detection rate of clinically significant disease in unselected men undergoing biopsy. © 2022 Elsevier Masson SAS. All rights reserved.

Surgical site infections: guidance for elective surgery during the SARS-CoV-2 pandemic - international recommendations and clinical experience.

BACKGROUND: The COVID-19 pandemic not only had an impact on public life and healthcare facilities in general, but also affected established surgical workflows for elective procedures. The strategy to protect patients and healthcare workers from infection by SARS-CoV-2 in surgical departments has needed step-by-step development. Based on the evaluation of international recommendations and guidelines, as well as personal experiences in a clinical 'hot spot' and in a 450-bed surgical clinic, an adapted surgical site infection (SSI) prevention checklist was needed to develop concise instructions, which described roles and responsibilities of healthcare professionals that could be used for wider guidance in pandemic conditions. METHOD: Publications of COVID-19-related recommendations and guidelines, produced by health authorities and organizations, such as WHO, US-CDC, ECDC, the American College of Surgery and the Robert Koch Institute, were retrieved, assessed and referenced up to 31st January 2020. Additionally, clinical personal experiences in Germany were evaluated and considered. RESULTS: Part 1 of this guidance summarizes the experience of a tertiary care, surgical centre which utilized redundant hospital buildings for immediate spatial separation in a 'hot spot' COVID-19 area. Part 2 outlines the successful screening and isolation strategy in a surgical clinic in a region of Germany with outbreaks in surrounding medical centres. Part 3 provides the synopsis of personal experiences and international recommendations suggested for implementation during the COVID-19 pandemic. CONCLUSION: Understanding of COVID-19, and SARS-CoV-2-related epidemiology, is constantly and rapidly changing, requiring continuous adaptation and re-evaluation of recommendations. Established national and local guidelines for continuation of surgical services and prevention of SSI require ongoing scrutiny and focused implementation. This manuscript presents a core facility checklist to support medical institutions to continue their clinical and surgical work during the COVID-19 pandemic.

[Instillation therapies for urothelial carcinoma of the upper urinary tract]. / Instillationstherapien beim Urothelkarzinom des oberen Harntraktes.

Traditionally, urothelial carcinoma of the upper urinary tract was a clear indication for radical nephroureterectomy with bladder cuff excision. It has been shown that in well-selected patients and depending on tumor stage, a kidney-sparing approach can be pursued with good oncological outcome and equivalent to the radical approach. The prevention of local and bladder recurrences is an important factor. Instillation therapies with bacillus Calmette-Guérin and/or mitomycin C have been successfully used to this end. Due to the low incidence of upper tract urothelial cancer and due to the usually retrospective nature of existing literature, however, data is limited. In this article, we provide a review of the indication, technical execution and results of instillation therapies of the upper urinary tract.

Development of a combined OCT-Raman probe for the prospective in vivo clinical melanoma skin cancer screening.

A combined optical coherence tomography (OCT)-Raman probe was designed and built into a spectral domain OCT head, and its performance was evaluated and compared to the most common Raman probe setups, based on a fiber bundle and confocal free space optics. Due to the use of the full field of view of an OCT scanning lens, the combined probe has a superior performance within maximum permissible exposure limits, compared to the other two probes. Skin Raman spectra, recorded in vivo, further prove the feasibility of the OCT-Raman probe for the future in vivo clinical applications in skin cancer screening.

Structure-based design of 3-carboxy-substituted 1,2,3,4-tetrahydroquinolines as inhibitors of myeloid cell leukemia-1 (Mcl-1).

Mcl-1 has recently emerged as an attractive target to expand the armamentarium in the war on cancer. Using structure-based design, 3-carboxy-substituted 1,2,3,4-tetrahydroquinolines were developed as a new chemotype to inhibit the Mcl-1 oncoprotein. The most potent compound inhibited Mcl-1 with a Ki of 120 nM, as determined by a fluorescence polarization competition assay. Direct binding was confirmed by 2D (1)H-(15)N HSQC NMR spectroscopy with (15)N-Mcl-1, which indicated that interactions with R263 and T266, and occupation of the p2 pocket are likely responsible for the potent binding affinity. The short and facile synthetic chemistry to access target molecules is expected to mediate lead optimization.

[Skin necrosis during long-term fluindione treatment revealing protein C deficiency]. / Nécroses cutanées tardives sous fluindione révélant un déficit en protéine C.

BACKGROUND: Cutaneous necrosis is a rare complication of vitamin K antagonist therapy. It presents as cutaneous hemorrhagic necrosis and usually occurs at the start of treatment. We describe an atypical case of recurrent skin necrosis after two years of treatment with fluindione. CASE REPORT: A 70-year old woman with a history of venous thromboembolism and obesity presented with a large haemorrhagic necrosis of the abdominal wall. She had been treated with fluindione for two years. Genetic protein C deficiency was discovered. Resumption of vitamin K antagonist therapy was followed by recurrence of skin necrosis despite concomitant administration of heparin. Treatment with vitamin K antagonists could not be continued. DISCUSSION: This observation is unusual due to the late onset of skin necrosis. The condition usually begins shortly after initiation of vitamin K antagonist therapy, generally between the third and the sixth day of treatment. It is due to a transient hypercoagulable state in patients with protein C deficiency or, in rare cases, protein S deficiency. This late-onset skin necrosis, occurring many years after initiation of anticoagulant therapy, may be explained by a sudden worsening of pre-existing protein C deficiency due to infectious and iatrogenic factors.

Comparative effectiveness of cisplatin-based and carboplatin-based chemotherapy for treatment of advanced urothelial carcinoma.

BACKGROUND: Cisplatin-based chemotherapy is a standard treatment of metastatic urothelial carcinoma (UC), though carboplatin-based chemotherapy is frequently substituted due to improved tolerability. Because comparative effectiveness in clinical outcomes of cisplatin- versus carboplatin-based chemotherapy is lacking, a meta-analysis was carried out. METHODS: PubMed was searched for articles published from 1966 to 2010. Eligible studies included prospective randomized trials evaluating cisplatin- versus carboplatin-based regimens in patients with metastatic UC. Individual patient data were not available and survival data were inconsistently reported. Therefore, the analysis focused on overall response (OR) and complete response (CR) rates. The Mantel-Haenszel method was used for combining trials and calculating pooled risk ratios (RRs). RESULTS: A total of 286 patients with metastatic UC from four randomized trials were included. Cisplatin-based chemotherapy was associated with a significantly higher likelihood of achieving a CR [RR = 3.54; 95% confidence interval (CI) 1.48-8.49; P = 0.005] and OR (RR = 1.34; 95% CI 1.04-1.71; P = 0.02). Survival end points could not be adequately assessed due to inconsistent reporting among trials. CONCLUSIONS: Cisplatin-based, as compared with carboplatin-based, chemotherapy significantly increases the likelihood of both OR and CR in patients with metastatic UC. The impact of improved response proportions on survival end points could not be assessed.

Esophageal capsule endoscopy for evaluation of patients with chronic gastroesophageal reflux symptoms: findings and its image quality.

Esophageal capsule endoscopy (ECE) may offer an alternative approach to visualize esophageal lesions associated with gastroesophageal reflux (GER) disease. The objective of this study was to report the ECE findings in patients with GER symptoms and validate a new scoring system to assess ECE video quality. Five hundred two ECE were performed in patients with GER symptoms. We devised a new grading scale called ECE Utility score to assess the quality of images using five different parameters: anatomic landmarks visualized, esophageal transit time, image quality, illumination, and artifacts. The ECE cases were independently scored by two interpreters in a randomized, blinded fashion. Reflux esophagitis was diagnosed via ECE in 254 patients (50.5%). We identified 12 cases (2.4%) with suspected Barrett's esophagus and all of them had endoscopic evidence of Barrett's esophagus on esophagogastroduodenoscopy. Histologic confirmation Barrett's esophagus was found in six patients and dysplasia was found in one patient. From the 502 cases, mean ± standard deviation total ECE Utility score was 8.89 ± 0.96 for interpreter 1 and 8.96 ± 0.93 for interpreter 2. The concordance rate between the two interpreters for the ECE Utility score ranged from 75.9-96.8% across the parameters and the Pearson correlation rate of the total score was 0.81. ECE is shown to be a simple noninvasive valuable technique for evaluating esophageal mucosa and producing high quality images in patients with GER symptoms. ECE can help as an alternative screening tool for diagnosing Barrett's esophagus.

Surfactant without intubation in preterm infants with respiratory distress: first multi-center data.

BACKGROUND: Recently in a report of a single center a method has been described to apply surfactant via a thin endotracheal catheter to very low birth weight infants spontaneously breathing with nasal continuous positive airway pressure. We now analyzed available multicenter data. PATIENTS AND METHODS: In a multicenter study investigating genetic risk factors, clinical and outcome data and data of antenatal and postnatal treatment of infants with a birth weight below 1,500 g were prospectively recorded. The measures of infants treated with the new method of surfactant application were compared to those of infants who received standard care. The analysis was restricted to infants with a gestational age below 31 weeks (n=1,541). RESULTS: 319 infants were treated with the new method and 1,222 with standard care. The need for mechanical ventilation during the first 72 h (29% vs. 53%, p<0.001), the rate of bronchopulmonary dysplasia defined as oxygen at 36 weeks of postmenstrual age (10.9 % vs. 17.5%, p=0.004) and the rate of death or bronchopulmonary dysplasia were significantly lower in the treatment group than in the standard care group. Surfactant, theophyllin, caffeine and doxapram were significantly more often and analgetics, catecholamines and dexamethasone were significantly less frequently used in the treatment group. CONCLUSIONS: A new method of surfactant application was associated with a lower prevalence of mechanical ventilation and better pulmonary outcome. A prospective controlled trial is required to determine whether this approach is superior to standard care.

[Primary ciliary dyskinesia causing neonatal respiratory distress]. / Primäre Ziliendyskinesie als Ursache neonataler Atemnot.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a hereditary disorder of structure and function of the cilia of respiratory epithelium of the upper and lower airways. Prevalence is estimated with 1:15 000 to 1:30 000 births. We present a newborn infant with respiratory distress caused by PCD. PATIENT: On the first day of life, the male newborn developed dyspnoe and cyanosis, so that CPAP and short term ventilation was necessary. Varying atelectasis impressed on the chest radiographs and the diagnosis of PCD was made by nasal brush biopsies. Causative is a lack of the inner dynein arms of the cilia. The clinical features of newborns with the diagnoses of PCD are listed and compared with the own case. CONCLUSION: PCD is a rare cause of neonatal respiratory distress and should be considered in term infants with unknown and prolonged course even if Situs inversus is lacking.

BNCT for skin melanoma in extremities: updated Argentine clinical results.

As part of phase I/II melanoma BNCT clinical trial conducted in Argentina in a cooperative effort of the Argentine Atomic Energy Commission (CNEA) and the Oncology Institute Angel H. Roffo (IOAHR), 7 patients (6 female-1 male) received eight treatment sessions covering ten anatomical areas located in extremities. Mean age of the patients was 64 years (51-74). The treatments were performed between October 2003 and June 2007. All patients presented multiple subcutaneous skin metastases of melanoma and received an infusion containing approximately 14 gr/m(2) of (10)borophenyl-alanine (BPA) followed by the exposition of the area to a mixed thermal-epithermal neutron beam at the RA-6 reactor. The maximum prescribed dose to normal skin ranged from 16.5 to 24 Gy-Eq and normal tissue administered dose varied from 15.8 to 27.5 Gy-Eq. Considering evaluable nodules, 69.3% of overall response and 30.7% of no changes were seen. The toxicity was acceptable, with 3 out of 10 evaluable areas showing ulceration (30% toxicity grade 3).

Tumor control and normal tissue complications in BNCT treatment of nodular melanoma: a search for predictive quantities.

A previous work concerning tumor control and skin damage in cutaneous melanoma treatments with BNCT has been extended to include doses, volumes and responses of 104 subcutaneous lesions from all patients treated in Argentina. Acute skin reactions were also scored for these patients, and cumulative dose-area histograms and dose-based figures of merit for skin were calculated. Broadening the tumor response analysis with the latest data showed that the (minimum or mean) tumor dose is not a good predictor of the observed clinical outcome by itself. However, when the tumor volume was included in the model as second explicative variable, the dose increases its significance and becomes a critical variable jointly with the volume (p-values<0.05). A preliminary analysis to estimate control doses for two groups of tumor sizes revealed that for small tumor volumes (< 0.1cm(3)) doses greater than 20 Gy-Eq produce a high tumor control (> 80%). However, when tumor volumes are larger than 0.1cm(3), control is moderate (< 40%) even for minimum doses up to 40 Gy-Eq. Some quantities based on skin doses, areas and complication probabilities were proposed as candidates for predicting the severity of the early skin reactions. With the current data, all the evaluated figures of merit derived similar results: ulceration is present among the cases for which these quantities take the highest values.

Dynamic infrared imaging of cutaneous melanoma and normal skin in patients treated with BNCT.

We recently initiated a program aimed to investigate the suitability of dynamic infrared imaging for following-up nodular melanoma patients treated with BNCT. The reason that makes infrared imaging attractive is the fact that it constitutes a functional and non-invasive imaging method, providing information on the normal and abnormal physiologic response of the nervous and vascular systems, as well as the local metabolic rate and inflammatory processes that ultimately appear as differences in the skin temperature. An infrared camera, with a focal plane array of 320 x 240 uncooled ferroelectric detectors is employed, which provides a video stream of the infrared emission in the 7-14 microm wavelength band. A double blackbody is used as reference for absolute temperature calibration. After following a protocol for patient preparation and acclimatization, a basal study is performed. Subsequently, the anatomic region of interest is subjected to a provocation test (a cold stimulus), which induces an autonomic vasoconstriction reflex in normal structures, thus enhancing the thermal contrast due to the differences in the vasculature of the different skin regions. Radiation erythema reactions and melanoma nodules possess typically a faster temperature recovery than healthy, non-irradiated skin. However, some other non-pathological structures are also detectable by infrared imaging, (e.g. scars, vessels, arteriovenous anastomoses and injuries), thus requiring a multi-study comparison in order to discriminate the tumor signal. Besides the superficial nodules, which are readily noticeable by infrared imaging, we have detected thermal signals that are coincident with the location of non-palpable nodules, which are observable by CT and ultrasound. Diffuse regions of fast temperature recovery after a cold stimulus were observed between the third and sixth weeks post-BNCT, concurrent with the clinical manifestation of radiation erythema. The location of the erythematous visible and infrared regions is consistent with the 3D dosimetry calculations.