Allelic imbalance at 1p36 may predict prognosis of chemoradiation therapy for bladder preservation in patients with invasive bladder cancer

Invasive bladder cancers have been treated by irradiation combined with cis- platinum (CDDP) as a bladder preservative option. The aim of this study was to find a marker for predicting patient outcome as well as clinical response after chemoradiation therapy (CRT) by investigating allelic loss of apoptosis-related genes. A total of 67 transitional cell carcinomas of the bladder treated by CRT (median dose: 32.4 Gy of radiation and 232 mg of CDDP) were studied. We investigated allelic imbalances at 14 loci on chromosomes 17p13 and 1p36 including the p53 and p73 gene regions by fluorescent multiplex PCR based on DNA from paraffin-embedded tumour specimens and peripheral blood. The response to CRT was clinical response (CR) in 21 patients (31%), partial response (PR) in 31 (46%), and no change(NC) in 15 (22%). There was no statistical correlation between treatment response and clinical parameters, such as tumour grade, stage, radiation dose, or CDDP dose. The frequencies of allelic imbalance for TP53 and TP73 were 21 and 56%, respectively; neither was correlated with clinical treatment response and tumour stage or grade. There was no statistical correlation between treatment response and allelic imbalance at the other 12 loci. We found a significant correlation between cancer-specific survival and an imbalance of D1S243 (P=0.0482) or TP73 (P=0.0013) using a Log-rank test, although other loci including TP53 did not correlate with survival (P=0.4529 Multivariate analysis showed performance status (P=0.0047), recurrence (P=0.0017), and radiation doses (P=0.0468) were independent predictive factors for cancer-specific survival. However, an allelic imbalance of TP73 was the most remarkable independent predictive factor of poor patient survival (P=0.0002, risk ratio: 3382). Our results suggest that the allelic loss of the p73 gene predicts a clinical outcome of locally advanced bladder cancer when treated by CRT

Intraoperative ultrasound-guided iodine-125 seed implantation for unresectable pancreatic carcinoma

<p>Abstract</p> <p>Background</p> <p>To assess the feasibility and efficacy of using ¹²⁵I seed implantation under intraoperative ultrasound guidance for unresectable pancreatic carcinoma.</p> <p>Methods</p> <p>Fourteen patients with pancreatic carcinoma that underwent laparotomy and considered unresectable were included in this study. Nine patients were pathologically diagnosed with Stage II disease, five patients with Stage III disease. Fourteen patients were treated with ¹²⁵I seed implantation guided by intraoperative ultrasound and received D₉₀of ¹²⁵I seeds ranging from 60 to 140 Gy with a median of 120 Gy. Five patients received an additional 35–50 Gy from external beam radiotherapy after seed implantation and six patients received 2–6 cycles of chemotherapy.</p> <p>Results</p> <p>87.5% (7/8) of patients received partial to complete pain relief. The response rate of tumor was 78.6%, One-, two-and three-year survival rates were 33.9% and 16.9%, 7.8%, with local control of disease achieved in 78.6% (11/14), and the median survival was 10 months (95% CI: 7.7–12.3).</p> <p>Conclusion</p> <p>There were no deaths related to ¹²⁵I seed implant. In this preliminary investigation, ¹²⁵I seed implant provided excellent palliation of pain relief, local control and prolong the survival of patients with stage II and III disease to some extent.</p

Long-term results of a phase II study of synchronous chemoradiotherapy in advanced muscle invasive bladder cancer.

We conducted a phase I/II study investigating synchronous chemoradiotherapy with mitomycin C and infusional 5-fluorouracil (5-FU) in muscle invasive bladder cancer. Early dose escalation results were previously published. We report the long-term toxicity and efficacy results with the optimised regimen. Patients with muscle invasive bladder cancer with glomerular filtration rate >25 ml min(-1) were eligible. Mitomycin (12 mg m(-2) on day 1 only) and infusional 5-FU (500 mg m(-2) day(-1)) for 5 days were administered during weeks 1 and 4 of radiotherapy of 55 Gy in 20 fractions. A total of 41 patients were enrolled, median age was 68 years, 33 were male and eight female patients. Out of the 41 patients, 20 (49%) had hydronephrosis at presentation and 25 (62%) had T3b or T4 disease. Four patients experienced Grade III thrombocytopenia and three patients had Grade III neutropenia. There were no episodes of febrile neutropenia. Four patients experienced Grade III diarrhoea and 1 Grade III urgency and dysuria. Six patients did not undergo cystoscopic evaluation due to early metastatic spread although there was no clinical suggestion of bladder failure. In all, out of 35 evaluable patients, 25 (71%) had macroscopic complete response at 3-month cystoscopy, and biopsy confirmed in 24 out of 25. A total of 16 (39%) patients remain alive with a median follow-up of 50.7 (range 23.5-68.8) months, 14 with a functioning bladder with no reported long-term treatment-related bladder or bowel toxicity. Five out of 41 patients have undergone salvage cystectomy: two for persistent CIS, two T1 and one muscle invasive recurrence. Four patients have received intravesical chemotherapy, of whom two remain alive with a functioning bladder. Overall 12-, 24- and 60-month (m) survival rates were 68, 49 and 36%. Local and distant progression free rates were 82 and 86% at 12-m and 79 and 75% at 24-m. Organ preservation using multimodality therapy is feasible and safe, even in patients with poor renal reserve, and does not compromise salvage therapies. A national phase III trial BC2001 (www.bc2001.org.uk) exploring the effects of synchronous chemoradiotherapy with this regimen is currently recruiting

Serum neutralization profiles of straw-colored fruit bats (Eidolon helvum) in Makurdi (Nigeria), against four lineages of Lagos bat lyssavirus

Lagos bat lyssavirus (LBV) comprising four lineages (A, B, C and D) can potentially cause the fatal disease rabies. Although LBV-B was initially isolated in Nigeria in 1956, there is no information on LBV lineages circulating in Nigeria. This study was undertaken for the first time to measure the neutralizing antibodies against four lineages of LBVs in straw-colored fruit bats (Eidolon helvum) in Makurdi, Nigeria. Serum samples (n = 180) collected during two periods (November 2017–March 2018 and November 2018–March 2019) from terminally bled bats captured for human consumption were tested using a modified fluorescent antibody virus neutralization (mFAVN) assay. A high proportion of bat sera (74%) neutralized at least one lineage of LBV (with reciprocal titers from 9 to >420.89) and most of them neutralized LBV-A (63%), followed by LBV-D (49%), LBV-C (45%) and LBV-B (24%). The majority of positive sera (75%, n = 100) neutralized multiple LBV lineages while the remaining 25% (n = 33) neutralized only a single lineage, i.e., LBV-A (n = 23), LBV-D (n = 8) and LBV-C (n = 2). None exclusively neutralized LBV-B. The results suggest that exposure to LBV is common in E. helvum and that LBV-A (but not LBV-B) is likely to be circulating in this region of Nigeria.The UK Department for Environment, Food and Rural Affairs (Defra), the Scottish Government and the Welsh Government, the European Union’s Horizon 2020 research and innovation program and University of Pretoria Doctoral Research Bursary.https://www.mdpi.com/journal/virusesdm2022Veterinary Tropical Disease

Serum Neutralization Profiles of Straw-Colored Fruit Bats (Eidolon helvum) in Makurdi (Nigeria), against Four Lineages of Lagos Bat Lyssavirus

Lagos bat lyssavirus (LBV) comprising four lineages (A, B, C and D) can potentially cause the fatal disease rabies. Although LBV-B was initially isolated in Nigeria in 1956, there is no information on LBV lineages circulating in Nigeria. This study was undertaken for the first time to measure the neutralizing antibodies against four lineages of LBVs in straw-colored fruit bats (Eidolon helvum) in Makurdi, Nigeria. Serum samples (n = 180) collected during two periods (November 2017–March 2018 and November 2018–March 2019) from terminally bled bats captured for human consumption were tested using a modified fluorescent antibody virus neutralization (mFAVN) assay. A high proportion of bat sera (74%) neutralized at least one lineage of LBV (with reciprocal titers from 9 to >420.89) and most of them neutralized LBV-A (63%), followed by LBV-D (49%), LBV-C (45%) and LBV-B (24%). The majority of positive sera (75%, n = 100) neutralized multiple LBV lineages while the remaining 25% (n = 33) neutralized only a single lineage, i.e., LBV-A (n = 23), LBV-D (n = 8) and LBV-C (n = 2). None exclusively neutralized LBV-B. The results suggest that exposure to LBV is common in E. helvum and that LBV-A (but not LBV-B) is likely to be circulating in this region of Nigeria

Bladder Sparing Approaches for Muscle-Invasive Bladder Cancers.

OPINION STATEMENT: Organ preservation has been increasingly utilised in the management of muscle-invasive bladder cancer. Multiple bladder preservation options exist, although the approach of maximal TURBT performed along with chemoradiation is the most favoured. Phase III trials have shown superiority of chemoradiotherapy compared to radiotherapy alone. Concurrent chemoradiotherapy gives local control outcomes comparable to those of radical surgery, but seemingly more superior when considering quality of life. Bladder-preserving techniques represent an alternative for patients who are unfit for cystectomy or decline major surgical intervention; however, these patients will need lifelong rigorous surveillance. It is important to emphasise to the patients opting for organ preservation the need for lifelong bladder surveillance as risk of recurrence remains even years after radical chemoradiotherapy treatment. No randomised control trials have yet directly compared radical cystectomy with bladder-preserving chemoradiation, leaving the age-old question of superiority of one modality over another unanswered. Radical cystectomy and chemoradiation, however, must be seen as complimentary treatments rather than competing treatments. Meticulous patient selection is vital in treatment modality selection with the success of recent trials within the field of bladder preservation only being possible through this application of meticulous selection criteria compared to previous decades. A multidisciplinary approach with radiation oncologists, medical oncologists, and urologists is needed to closely monitor patients who undergo bladder preservation in order to optimise outcomes

Searching for phenotypic causal networks involving complex traits: an application to European quail

<p>Abstract</p> <p>Background</p> <p>Structural equation models (SEM) are used to model multiple traits and the casual links among them. The number of different causal structures that can be used to fit a SEM is typically very large, even when only a few traits are studied. In recent applications of SEM in quantitative genetics mixed model settings, causal structures were pre-selected based on prior beliefs alone. Alternatively, there are algorithms that search for structures that are compatible with the joint distribution of the data. However, such a search cannot be performed directly on the joint distribution of the phenotypes since causal relationships are possibly masked by genetic covariances. In this context, the application of the Inductive Causation (IC) algorithm to the joint distribution of phenotypes conditional to unobservable genetic effects has been proposed.</p> <p>Methods</p> <p>Here, we applied this approach to five traits in European quail: birth weight (BW), weight at 35 days of age (W35), age at first egg (AFE), average egg weight from 77 to 110 days of age (AEW), and number of eggs laid in the same period (NE). We have focused the discussion on the challenges and difficulties resulting from applying this method to field data. Statistical decisions regarding partial correlations were based on different Highest Posterior Density (HPD) interval contents and models based on the selected causal structures were compared using the Deviance Information Criterion (DIC). In addition, we used temporal information to perform additional edge orienting, overriding the algorithm output when necessary.</p> <p>Results</p> <p>As a result, the final causal structure consisted of two separated substructures: BW→AEW and W35→AFE→NE, where an arrow represents a direct effect. Comparison between a SEM with the selected structure and a Multiple Trait Animal Model using DIC indicated that the SEM is more plausible.</p> <p>Conclusions</p> <p>Coupling prior knowledge with the output provided by the IC algorithm allowed further learning regarding phenotypic causal structures when compared to standard mixed effects SEM applications.</p