A Single Dose of Intrathecal Morphine Without Local Anesthetic Provides Long-Lasting Postoperative Analgesia After Radical Prostatectomy and Nephrectomy.

PURPOSE: Pain after open urological procedures is often intense. The aim of the study was to compare the efficacy of intrathecal morphine with systemic analgesia approaches. DESIGN: Prospective, randomized, single-blind controlled study. METHODS: Patients undergoing open prostatectomy or nephrectomy were randomly divided into the intervention group or the control group. Patients in the intervention group received morphine 250 mcg in 2.5 mL saline intrathecally. Anesthesia was identical in both groups. All patients were admitted to the intensive care unit (ICU) postoperative and received paracetamol 1 g intravenously every 6 hours and diclofenac 75 mg intramuscularly every 12 hours. If postoperative pain exceeded four on the numeric rating scale, morphine 10 mg was administered subcutaneously. Pain intensity, time to first dose of morphine, morphine doses, and side effects were recorded. FINDINGS: In total, 41 patients were assigned to the intervention group and 57 to the control group. The time to administration of the first dose of morphine was significantly (P < .001) longer in the intervention group when compared to controls. This observation was also noted individually for patients undergoing nephrectomy (36.86 hours vs 4.06 hours) and prostatectomy (33.13 hours vs 4.5 hours). Many patients did not need opioids after surgery in the intervention group (nephrectomy 72% vs 3%, prostatectomy 75% vs 4.5%, P < .001). There was no significant difference in the incidence of side effects. CONCLUSIONS: The results of our study confirmed that preoperative intrathecal morphine provides long-lasting analgesia and reduces the need for postoperative systemic administration of opioids. Adverse effects are minor and comparable between groups.

Mitochondrially targeted tamoxifen as anticancer therapy: case series of patients with renal cell carcinoma treated in a phase I/Ib clinical trial.

Mitochondrially targeted anticancer drugs (mitocans) that disrupt the energy-producing systems of cancer are emerging as new potential therapeutics. Mitochondrially targeted tamoxifen (MitoTam), an inhibitor of mitochondrial respiration respiratory complex I, is a first-in-class mitocan that was tested in the phase I/Ib MitoTam-01 trial of patients with metastatic cancer. MitoTam exhibited a manageable safety profile and efficacy; among 37% (14/38) of responders, the efficacy was greatest in patients with metastatic renal cell carcinoma (RCC) with a clinical benefit rate of 83% (5/6) of patients. This can be explained by the preferential accumulation of MitoTam in the kidney tissue in preclinical studies. Here we report the mechanism of action and safety profile of MitoTam in a case series of RCC patients. All six patients were males with a median age of 69 years, who had previously received at least three lines of palliative systemic therapy and suffered progressive disease before starting MitoTam. We recorded stable disease in four, partial response in one, and progressive disease (PD) in one patient. The histological subtype matched clear cell RCC (ccRCC) in the five responders and claro-cellular carcinoma with sarcomatoid features in the non-responder. The number of circulating tumor cells (CTCs) was evaluated longitudinally to monitor disease dynamics. Beside the decreased number of CTCs after MitoTam administration, we observed a significant decrease of the mitochondrial network mass in enriched CTCs. Two patients had long-term clinical responses to MitoTam, of 50 and 36 weeks. Both patients discontinued treatment due to adverse events, not PD. Two patients who completed the trial in November 2019 and May 2020 are still alive without subsequent anticancer therapy. The toxicity of MitoTam increased with the dosage but was manageable. The efficacy of MitoTam in pretreated ccRCC patients is linked to the novel mechanism of action of this first-in-class mitochondrially targeted drug.

Surgical site infections after stabilization of pelvic ring injuries: a retrospective analysis of risk factors and a meta-analysis of similar studies.

PURPOSE: Pelvic ring fractures requiring surgical stabilization are severe injuries. Surgical site infections occurring after stabilization of the pelvis are serious complications, requiring complex and multidisciplinary treatment. METHODS: This is a retrospective observational study from a level I trauma centre. One hundred and ninety-two patients who underwent stabilization of closed pelvic ring injuries without signs of pathological fracture were selected for inclusion into the study. After excluding seven patients for having incomplete data, the final study group consisted of 185 patients (117 men and 68 women). Basic epidemiologic data and potential risk factors were recorded and analyzed by Cox regression, Kaplan-Meier curves, and risk ratios in 2 × 2 tables. Categorical variables were compared by Fisher exact tests and chi squared tests. Parametric variables were analyzed with Kruskal-Wallis tests with post hoc Wilcoxon tests. RESULTS: Surgical site infections occurred in 13% of the study group (24 from 185). Eighteen infections occurred in men (15.4%) and six in women (8.8%). There were two significant risk factors in women: age over 50 years (p = 0.0232) and concomitant urogenital trauma (p = 0.0104). The common risk ratio for both these factors was 212.59 (8.78-5148.68), p = 0.0010. No significant risk factors were identified in men despite younger men having a higher incidence of infection (p = 0.1428). CONCLUSION: Overall rate of infectious complications was higher than in the literature, but this might be caused by inclusion of all patients regardless of surgical strategy. Higher age in women and lower age in men were associated with higher infection rates. Concomitant urogenital trauma was a significant risk factor in women.

The Effectiveness of Post-Vaccination and Post-Infection Protection in the Hospital Staff of Three Prague Hospitals: A Cohort Study of 8-Month Follow-Up from the Start of the COVID-19 Vaccination Campaign (COVANESS).

Continuous assessment of the effectiveness of approved COVID-19 vaccines is crucial to gain an insight into the longer-term impact on health outcomes, and eventually boosting public confidence. For this reason, we conducted a multicenter, retrospective cohort study using data on infection and vaccination rates among employees of three Prague hospitals in the period between 27 December 2020 and 31 August 2021. The post-vaccination and post-infection protectiveness were assessed in a total of 11,443 hospital workers who were followed up for more than 14 days either after their Comirnaty vaccination or study enrolment, depending on their previous SARS-CoV-2 infection. The effectiveness of full vaccination against any SARS-CoV-2 infection achieved 88.3% (83.2-91.8%) over the eight months of follow-up, a figure not much different from the 92.5% (76.5-97.6%) level of protection built by a previous infection. Despite this, the post-vaccination level of protection declined to about 65% between June and August. No case of breakthrough infection was registered among hospital workers having received one or two vaccine doses more than three months after previous infection. The eight-month effectiveness of the Comirnaty vaccine exhibited a declining trend requiring a new booster dose. The need for vaccination in the previously infected employees was not demonstrated conclusively in this study.

The role of the vascular surgery in oncosurgery.

Surgical resection remains the cornerstone for the curative treatment of oncological disease. In a situation when a tumour encases a critical arterial or venous structure, long term oncological control may be achieved only through careful preoperative planning within a multidisciplinary team incorporating oncological and vascular specialists. The present review addresses the principles in planning oncovascular surgery, describes the oncovascular procedure in pancreatic, liver, renal and endometriosis cancer as well as vascular involvement in retroperitoneal soft sarcoma and sarcoma in lower extremity. In conclusion, the present review highlights that major vessel involvement of a tumour mass should not necessarily be considered as a barrier to en bloc resection and hence curative oncosurgery procedure.

Detection of Circulating Tumor Cells in Renal Cell Carcinoma: Disease Stage Correlation and Molecular Characterization.

The presence of circulating tumor cells (CTCs) in patients with solid tumors is associated with poor prognosis. However, there are limited data concerning the detection of CTCs in renal cell cancer (RCC). The aim of this study is to evaluate the presence of CTCs in peripheral blood of patients with RCC undergoing surgery (n = 186). CTCs were tested before and after surgery as well as during the follow-up period afterwards. In total 495 CTC testing in duplicates were provided. To enrich CTCs, a size-based separation protocol and tube MetaCell® was used. CTCs presence was evaluated by single cell cytomorphology based on vital fluorescence microscopy. Additionally, to standardly applied fluorescence stains, CTCs viability was controlled by mitochondrial activity. CTCs were detected independently on the sampling order in up to 86.7% of the tested blood samples in patients undergoing RCC surgery. There is higher probability of CTC detection with growing tumor size, especially in clear cell renal cell cancer (ccRCC) cases. Similarly, the tumor size corresponds with metastasis presence and lymph node positivity and CTC detection. This paper describes for the first-time successful analysis of viable CTCs and their mitochondria as a part of the functional characterization of CTCs in RCC.

Molecular Basis of Cisplatin Resistance in Testicular Germ Cell Tumors.

The emergence of cisplatin (CDDP) resistance is the main cause of treatment failure and death in patients with testicular germ cell tumors (TGCT), but its biologic background is poorly understood. To study the molecular basis of CDDP resistance in TGCT we prepared and sequenced CDDP-exposed TGCT cell lines as well as 31 primary patients' samples. Long-term exposure to CDDP increased the CDDP resistance 10 times in the NCCIT cell line, while no major resistance was achieved in Tera-2. Development of CDDP resistance was accompanied by changes in the cell cycle (increase in G1 and decrease in S-fraction), increased number of acquired mutations, of which 3 were present within ATRX gene, as well as changes in gene expression pattern. Copy number variation analysis showed, apart from obligatory gain of 12p, several other large-scale gains (chr 1, 17, 20, 21) and losses (chr X), with additional more CNVs found in CDDP-resistant cells (e.g., further losses on chr 1, 4, 18, and gain on chr 8). In the patients' samples, those who developed CDDP resistance and died of TGCT (2/31) showed high numbers of acquired aberrations, both SNPs and CNVs, and harbored mutations in genes potentially relevant to TGCT development (e.g., TRERF1, TFAP2C in one patient, MAP2K1 and NSD1 in another one). Among all primary tumor samples, the most commonly mutated gene was NSD1, affected in 9/31 patients. This gene encoding histone methyl transferase was also downregulated and identified among the 50 most differentially expressed genes in CDDP-resistant NCCIT cell line. Interestingly, 2/31 TGCT patients harbored mutations in the ATRX gene encoding a chromatin modifier that has been shown to have a critical function in sexual differentiation. Our research newly highlights its probable involvement also in testicular tumors. Both findings support the emerging role of altered epigenetic gene regulation in TGCT and CDDP resistance development.

Acute Urinary Retention in Aseptic Meningitis: Meningitis-retention Syndrome.

Here we present the case of a 50-year-old woman with acute urinary retention who was treated by the insertion of a permanent catheter. For associated headaches, fever and muscle and joint pain, the patient underwent neurologic examination, including lumbar puncture and magnetic resonance of head and spine. The results confirmed aseptic meningitis. Subsequently, the patient was hospitalized at the infectious disease clinic, where the permanent catheter was extracted after 5 days, with spontaneous micturition recovery and no post-void residual volume. The combination of aseptic meningitis and urinary retention is called meningitis-retention syndrome. This is a rare disease, which has been described only a few times in the literature.

Overexpression of TET dioxygenases in seminomas associates with low levels of DNA methylation and hydroxymethylation.

Germ cell tumors and particularly seminomas reflect the epigenomic features of their parental primordial germ cells (PGCs), including genomic DNA hypomethylation and expression of pluripotent cell markers. Because the DNA hypomethylation might be a result of TET dioxygenase activity, we examined expression of TET1-3 enzymes and the level of their product, 5-hydroxymethylcytosine (5hmC), in a panel of histologically characterized seminomas and non-seminomatous germ cell tumors. Expression of TET dioxygenase mRNAs was quantified by real-time PCR. TET1 expression and the level of 5hmC were examined immunohistochemically. Quantitative assessment of 5-methylcytosine (5mC) and 5hmC levels was done by the liquid chromatography-mass spectroscopy technique. We found highly increased expression of TET1 dioxygenase in most seminomas and strong TET1 staining in seminoma cells. Isocitrate dehydrogenase 1 and 2 mutations were not detected, suggesting the enzymatic activity of TET1. The levels of 5mC and 5hmC in seminomas were found decreased in comparison to non-seminomatous germ cell tumors and healthy testicular tissue. We propose that TET1 expression should be studied as a potential marker of seminomas and mixed germ cell tumors and we suggest that elevated expression of TET dioxygenase enzymes is associated with the maintenance of low DNA methylation levels in seminomas. This "anti-methylator" phenotype of seminomas is in contrast to the CpG island methylator phenotype (CIMP) observed in a fraction of tumors of various types.

Benign fibroepithelial polyp of the ureter.

Benign tumors of the ureter are rare and most often appear in the form of fibroepithelial polyps [1]. Fibroepithelial polyps represent from 2 to 6% of all benign tumors of the urinary tract [2]. The Authors report on two cases of fibroepithelial polyps of the ureter, which they treated between 1993-2009. One case was presented by acute urinary retention and gross hematuria. In the second case, hematuria and flank pain were observed. The first case was treated with open surgery and partial resection of the ureter, the second was treated endoscopically when the base of the polyp was well identified.