Non-muscle-invasive papillary urothelial carcinoma (NMIPUC) of the urinary bladder is the most common type of bladder cancer. Intravesical Bacille Calmette-Guerin (BCG) immunotherapy is applied in ...patients with a high risk of recurrence and progression of NMIPUC to muscle-invasive disease. However, the tumor relapses in about 30% of patients despite the treatment, raising the need for better risk stratification. We explored the potential of spatial distributions of immune cell subtypes (CD20, CD11c, CD163, ICOS, and CD8) within the tumor microenvironment to predict NMIPUC recurrence following BCG immunotherapy. Based on analyses of digital whole-slide images, we assessed the densities of the immune cells in the epithelial-stromal interface zone compartments and their distribution, represented by an epithelial-stromal interface density ratio (IDR). While the densities of any cell type did not predict recurrence, a higher IDR of CD11c (HR: 0.0012,
-value = 0.0002), CD8 (HR: 0.0379,
-value = 0.005), and ICOS (HR: 0.0768,
-value = 0.0388) was associated with longer recurrence-free survival (RFS) based on the univariate Cox regression. The history of positive repeated TUR (re-TUR) (HR: 4.93,
-value = 0.0001) and T1 tumor stage (HR: 2.04,
-value = 0.0159) were associated with shorter RFS, while G3 tumor grade according to the 1973 WHO classification showed borderline significance (HR: 1.83,
-value = 0.0522). In a multivariate analysis, the two models with a concordance index exceeding 0.7 included the CD11c IDR in combination with either a history of positive re-TUR or tumor stage. We conclude that the CD11c IDR is the most informative predictor of NMIPUC recurrence after BCG immunotherapy. Our findings highlight the importance of assessment of the spatial distribution of immune cells in the tumor microenvironment.
Bacille Calmette-Guerin (BCG) immunotherapy is the first-line treatment in patients with high-risk non-muscle invasive papillary urothelial carcinoma (NMIPUC), the most common type of bladder cancer. ...The therapy outcomes are variable and may depend on the immune response within the tumor microenvironment. In our study, we explored the prognostic value of CD8+ cell density gradient indicators across the tumor epithelium-stroma interface of NMIPUC.
Clinical and pathologic data were retrospectively collected from 157 NMIPUC patients treated with BCG immunotherapy after transurethral resection. Whole-slide digital image analysis of CD8 immunohistochemistry slides was used for tissue segmentation, CD8+ cell quantification, and the assessment of CD8+ cell densities within the epithelium-stroma interface. Subsequently, the gradient indicators (center of mass and immunodrop) were computed to represent the density gradient across the interface.
By univariable analysis of the clinicopathologic factors, including the history of previous NMIPUC, poor tumor differentiation, and pT1 stage, were associated with shorter RFS (
< 0.05). In CD8+ analyses, only the gradient indicators but not the absolute CD8+ densities were predictive for RFS (
< 0.05). The best-performing cross-validated model included previous episodes of NMIPUC (HR = 4.4492,
= 0.0063), poor differentiation (HR = 2.3672,
= 0.0457), and immunodrop (HR = 5.5072,
= 0.0455).
We found that gradient indicators of CD8+ cell densities across the tumor epithelium-stroma interface, along with routine clinical and pathology data, improve the prediction of RFS in NMIPUC.
Surgical treatment is widely applied curative approach for bladder cancer. White light cystoscopy (WLC) is currently used for intraoperative diagnostics of malignant lesions but has relatively high ...false-negative rate. Here we represent an application of label free fiber-based attenuated total reflection infrared spectroscopy (ATR IR) for freshly resected human bladder tissue examination for 54 patients. Defined molecular spectral markers allow to identify normal and urothelial carcinoma tissues. While methods of statistical analysis (Hierarchical cluster analysis (HCA) and Principal component analysis (PCA)) used for spectral data treatment allow to discriminate tissue types with 91% sensitivity and 96-98% specificity. In the present study the described method was applied for tissue examination under ex vivo conditions. However, after method validation the equipment could be translated from laboratory studies to in situ or even in vivo studies in operating room.
The limited reproducibility of the grading of non-muscle invasive papillary urothelial carcinoma (NMIPUC) necessitates the search for more robust image-based predictive factors. In a cohort of 157 ...NMIPUC patients treated with Bacille Calmette-Guérin (BCG) immunotherapy, we explored the multiple instance learning (MIL)-based classification approach for the prediction of 2-year and 5-year relapse-free survival and the multiple instance survival learning (MISL) framework for survival regression. We used features extracted from image patches sampled from whole slide images of hematoxylin-eosin-stained transurethral resection (TUR) NPMIPUC specimens and tested several patch sampling and feature extraction network variations to optimize the model performance. We selected the model showing the best patient survival stratification for further testing in the context of clinical and pathological variables. MISL with the multiresolution patch sampling technique achieved the best patient risk stratification (concordance index = 0.574,
= 0.010), followed by a 2-year MIL classification. The best-selected model revealed an independent prognostic value in the context of other clinical and pathologic variables (tumor stage, grade, and presence of tumor on the repeated TUR) with statistically significant patient risk stratification. Our findings suggest that MISL-based predictions can improve NMIPUC patient risk stratification, while validation studies are needed to test the generalizability of our models.
Colorectal cancer (CRC) is one of the most common malignancies worldwide. Patients with CRC may need chemotherapy (CTx) in a neoadjuvant, adjuvant or palliative setting through the course of the ...disease. Unfortunately, its effect is limited by chemoresistance and chemotoxicity. Novel more effective and non-toxic CTx regimens are needed to further improve CRC treatment outcomes. Thus, the present study was designed to test the hypothesis that non-toxic sulforaphane (SF) is effective against CRC and has additive effects in combination with conventional 5-fluorouracil, oxaliplatin and folinic acid (FOLFOX) CTx in vitro. Highly metastatic human colon cancer cells, CX-1, and fibroblasts were treated with FOLFOX + or - SF. Cell viability was assessed using an MTT assay. The level of apoptosis and the expression of apoptotic proteins were measured by TUNEL assay and quantitative PCR analysis. Aldehyde dehydrogenase isoform 1 (ALDH1) and multidrug resistance protein 2 (MRP2) levels were evaluated. The ability of cells to form spheroids was measured in three-dimensional cell culture. SF alone and in combination with FOLFOX effectively decreased the viability of the CX-1 cells, promoted apoptosis within the CX-1 cells, prevented cellular spheroid formation and decreased ALDH1 activity. However, SF promoted MRP2 expression and protein levels. In conclusion, SF together with conventional FOLFOX has additive anticancer effects against highly metastatic human CRC in vitro. Key words: sulforaphane, CRC, FOLFOX, CX-1, CTx
Background and Objectives: Consequences of partial nephrectomy (PN), intraoperative hypotension (IOH) and postoperative neutrophil to lymphocyte ratio (NLR) may cause postoperative acute kidney ...injury (AKI) and in long-term-chronic kidney disease (CKD). Our study aimed to identify the AKI incidence after PN, to find clinically significant postoperative AKI and renal dysfunction, and to determine the predictor factors. Materials and Methods: A prospective observational study consisted of 91 patients who received PN with warm ischemia, and estimated preoperative glomerular filtration rate (eGFR) ≥ 60 mL/min and without abnormal albuminuria. Results: 38 (41.8%) patients experienced postoperative AKI. Twenty-one (24.1%) patients had CKD upstage after 1 year follow-up. Sixty-seven percent of CKD upstage patients had AKI 48 h after surgery and 11% after 2 months. All 15 (16.5%) patients with CKD had postoperative AKI. With IOH, OR 1.07, 95% CI 1.03−1.10 and p < 0.001, postoperative NLR after 48 h (OR 1.50, 95% CI 1.19−1.88, p < 0.001) was the major risk factor of AKI. In multivariate logistic regression analysis, the kidney’s resected part volume (OR 1.08, 95% CI 1.03−1.14, p < 0.001) and IOH (OR 1.10, 95% CI 1.04−1.15, p < 0.001) were retained as statistically significant prognostic factors for detecting postoperative renal dysfunction. The independent risk factor for clinically significant postoperative AKI was only IOH (OR, 1.06; p < 0.001). Only AKI with the CKD upstage group has a statistically significant effect (p < 0.0001) on eGFR 6 and 12 months after surgery. Conclusions: The presence of AKI after PN is not rare. IOH and NLR are associated with postoperative AKI. The most important predictive factor of postoperative AKI is an NLR of over 3.5. IOH is an independent risk factor for clinically significant postoperative AKI and together with kidney resected part volume effects postoperative renal dysfunction. Only clinically significant postoperative AKI influences the reduction of postoperative eGFR after 6 and 12 months.
Objective: Our study aimed to evaluate the success rate of ESWL and identify relevant treatment-specific factors affecting treatment outcomes, as well as to assess the accuracy of the updated Triple ...D scoring system and compare it with older systems. Material and Methods: A prospective study of 71 patients who received ESWL treatment for renal stones that were 5–15 mm in size was completed. The patient having no residual stones or residual stones lesser than 4 mm after ESWL was identified as a treatment success. Univariate and multivariate logistic regression and ROC curves were used to identify important factors for treatment outcomes. Results: Successful treatment was achieved for 66.2% of patients. The stone volume (SV), mean stone density (MD), and delivered power to the stone volume unit ratio (SMLI/SV) were defined as the most critical factors influencing ESWL success. An updated Triple D score system with a, SMLI/SV ratio could be an alternative to older systems and reach an even higher accuracy. A limitation of this study is the limited sample size due to the COVID-19 pandemic. Conclusions: Our results show that the three factors that most influence the success of ESWL are the stone size, mean stone density, and SMLI/SV ratio. Based on this, we present a simple updated triple D score system to predict ESWL success, which could be implemented in future clinical practice.
Current literature suggests various predictors related to the stone and patient, which could influence stone fragmentation and clearance rates.
To establish clinical characteristics of stone disease ...for patients undergoing extracorporeal shockwave lithotripsy (ESWL) which may predict the success of the procedure.
One hundred and nine patients with renal stone disease diagnosed by non-contrast computed tomography (NCCT) who underwent ESWL between January 2015 and December 2019 were included in the study. Endpoints: patient being stone free (SF) or when < 4 mm fragments were detected. Age, gender, location, skin-to-stone distance, maximum stone length, stone volume, stone surface area, mean stone Hounsfield units (HU) and highest HU score were explored in uni- and multivariate regression analysis.
Stone size revealed the highest prognostic power for ESWL failure, where OR for stone volume and stone surface area were 1.06 (1.03-1.10) and 1.04 (1.02-1.06), respectively (all p < 0.01) while a tendency was observed for skin-to-stone distance 1.02 (1.00-1.03). The amount of energy applied during the procedure to one cubic millimeter of stone volume (SMLI/stone volume) was predictive for treatment success (OR = 0.60, 95% CI: 0.41-0.87, p < 0.01). Stone volume (OR = 1.06, 95% CI: 1.00-1.14, p = 0.01) and stone surface area (OR = 1.03, 95% CI: 1.01-1.06, p = 0.02) remained as statistically significant prognostic factors for treatment failure.
Both greater stone volume and stone surface area, as well as lower power delivered per stone volume unit during the ESWL procedure, were found to be significant factors and could be useful to predict treatment failure.
: Experimental data suggest that melatonin decreases inflammatory changes after major liver resection, thus positively influencing the postoperative course. To assess the safety of a preoperative ...single dose of melatonin in patients undergoing major liver resection, a randomized controlled double‐blind pilot clinical trial with two parallel study arms was designed at the Department of General and Transplantation Surgery, Ruprecht‐Karls‐University, Heidelberg. A total of 307 patients, who were referred for liver surgery, were screened. One hundred and thirteen patients, for whom a major liver resection (≥3 segments) was scheduled, were eligible. Sixty‐three eligible patients refused to participate, and therefore, 50 patients were randomized. A preoperative single dose of melatonin (50 mg/kg BW) dissolved in 250 mL of milk was administered through the gastric tube after the intubation for general anesthesia. Controls were given the same amount of microcrystalline cellulose. Primary endpoint was safety. Secondary endpoints were postoperative complications. Melatonin was effectively absorbed with serum concentrations of 1142.8 ± 7.2 ng/mL (mean ± S.E.M.) versus 0.3 ± 7.8 ng/mL in controls (P < 0.0001). Melatonin treatment resulted in lower postoperative transaminases over the study period (P = 0.6). There was no serious adverse event in patients after melatonin treatment. A total of three infectious complications occurred in either group. A total of eight noninfectious complications occurred in five control patients, whereas three noninfectious complications occurred in three patients receiving preoperative melatonin (P = 0.3). There was a trend toward shorter ICU stay and total hospital stay after melatonin treatment. Therefore, a single preoperative enteral dose of melatonin is effectively absorbed and is safe and well tolerated in patients undergoing major liver surgery.
On June, 2023, Vilnius University Hospital Santaros Klinikos started robotic-assisted operations using VERSIUS robotic surgery system (CMR, Cambridge, UK) and performed 29 robotic surgeries within ...the first 3 weeks. This surgical system was purchased with funding from the European Regional Development Fund. Comprehensive three-month-long learning courses were organized for a total number of 32 persons, forming 8 independent teams, each consisting of 2 surgeons and 2 nurses. Learning courses consisted of online theoretical training modules, a one-week learning course including technical skills training with a simulator and dry runs as well as cadaveric surgical cases. Furthermore, an additional learning module included dry runs in the operating room prior to the first surgeries, following live and online proctored surgical cases. This enabled a rapid and smooth introduction of the robotic surgical system into clinical practice without putting patients at risk. Abdominal surgeons, urologists, and gynecologists have already performed surgeries using the VERSIUS surgical system and no major complications have been reported. Thoracic surgeons are underway to begin thoracic robotic-assisted surgeries, completing the multidisciplinary VERSIUS surgical system implementation process.
Our goal is to share initial experience with robotic VERSIUS surgical system and evaluate its implementation in Vilnius University Hospital Santaros Klinikos.
2023 m. birželio mėn. Vilniaus universiteto ligoninėje Santaros klinikose pradėtos atlikti robotinės operacijos, naudojant robotinės chirurgijos sistemą „Versius“ (CMR, Kembridžas, JK). Per pirmąsias tris savaites atliktos 29 robotinės operacijos. Sistema įsigyta panaudojus Europos regioninės plėtros fondo lėšas.
Išsamius 3 mėn. teorinius kursus išklausė ir praktiniuose mokymuose dalyvavo 32 Santaros klinikų medicinos darbuotojai. Jie suformavo 8 nepriklausomas komandas, sudarytas iš 2 chirurgų ir 2 slaugytojų. Mokymosi kursai apėmė: nuotolinius teorinio mokymo modulius; vienos savaitės mokymosi kursą, kurio metu lavinti techniniai įgūdžiai naudojant virtualiosios realybės simuliatorius; techninių įgūdžių mokymus, naudojant pilvo ertmės ir krūtinės ląstos ertmės operacijų muliažus; praktinius seminarus, per kuriuos buvo atliekamos operacijos, naudojant kadaverinius preparatus. Artėjant pirmosioms operacijoms, visos 8 komandos išėjo antrąjį mokymosi kursą operacinėje, naudodamiesi chirurginių įgūdžių lavinimo ir operacijų simuliavimo muliažais. Mokymų kursų pabaigoje atliktos kruopščiai suplanuotos pirmosios robotinės operacijos, dalyvaujant patyrusiems robotinės chirurgijos specialistams – mentoriams.
Kruopštus standartizuotas mokymosi procesas leido greitai ir sklandžiai įdiegti robotinę chirurgiją į klinikinę praktiką, nekeliant pavojaus pacientams. Naudodami chirurginę sistemą „Versius“, pilvo chirurgai, urologai ir ginekologai jau atliko reikšmingą kiekį operacijų, išvengdami didelių komplikacijų. Pastaruoju metu pirmąsias operacijas atliko ir krūtinės chirurgai. Taip Vilniaus universiteto ligoninėje Santaros klinikose baigiamas robotinės chirurgijos sistemos „Versius“ daugiadisciplinio diegimo procesas.
Straipsnio tikslas – pasidalyti pirmąja patirtimi, naudojant „Versius“ robotinės chirurgijos sistemą, ir įvertinti šios sistemos diegimo Vilniaus universiteto ligoninėje Santaros klinikose procesą.
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