Bladder preservation multimodality therapy as an alternative to radical cystectomy for treatment of muscle invasive bladder cancer

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? The subject of bladder preservation multimodality protocols in muscle invasive bladder TCC is not new. In our study, even in a highly selected group of patients, multimodality protocol with M‐VAC and radiation therapy achieved suboptimal results at 1 year. This emphasized the role of radical cystectomy as the gold standard treatment for invasive bladder TCC.

OBJECTIVE

• ? To evaluate the efficacy of a bladder preservation multimodality protocol for patients with operable carcinoma invading bladder muscle.

MATERIALS AND METHODS

• ? In this prospective study, we included 33 patients with transitional cell carcinoma (TCC) (T2 and T3, Nx, M0) who were amenable to complete transurethral resection.
• ? These patients refused radical cystectomy as their first treatment option. After maximum transurethral resection of bladder tumour (TURBT), all patients received three cycles of adjuvant chemotherapy in the form of methotrexate, vinblastin, adriamycin and cisplatin (MVAC) followed by radical radiotherapy.
• ? Four weeks later, all cases had radiological and cystoscopical re‐evaluation.
• ? Complete responders were considered to be those patients who had no evidence of residual tumour. All patients were subjected to a regular follow‐up by cystoscopy and tumour site biopsy conducted every 3 months. Abdomino‐pelvic computed tomography and chest X‐ray were conducted every 6 months.
• ? The study endpoint was the response to treatment after completion of the first year of follow‐up after therapy.

RESULTS

• ? Out of 33 eligible patients, a total of 28 patients completed the study treatment protocol. Their mean ± SD age was 56.7 ± 6 years. Trimodal therapy was well tolerated in most of cases, with no severe acute toxicities. After 12 months of follow‐up, a complete response was achieved in 39.3% and a partial response in 7.1%, with an overall response rate of 46.4%.
• ? By the end of the first year, disease‐free survival was reported in 39.3%, whereas 25% were still alive with their disease, giving an overall survival of 64.3% for all patients who maintained their intact, well functioning bladders.
• ? Tumour stage and completeness of transurethral resection of bladder tumour were the most important predictors of response and survival. T2 lesions had complete and partial response rates of 69.2% and 23%, respectively, whereas T3 lesions had rates of 40% and 13.3%, respectively (P= 0.001).
• ? The response rate in patients who had complete TURBT was 82.6% vs 20% in those with cystoscopic biopsy only (P= 0.001). In addition, disease‐free survival was 72.7% in T2 patients and 27.3% in T3 patients (P= 0.001).

CONCLUSION

• ? In the present study, bladder preservation protocol with MVAC and radical radiotherapy achieved suboptimal response rates at 1 year in patients with localized TCC invading bladder muscle. Patients with solitary T2 lesions that are amenable to complete TURBT achieved the best response rates. Longer follow‐up is needed to verify these results. Patients with localized disease should be encouraged for radical cystectomy, which achieved better results.

     

Noninvasive work of breathing improves prediction of post-extubation outcome

Purpose  

We hypothesized that non-invasively determined work of breathing per minute (WOB_N/min) (esophageal balloon not required) may be useful for predicting extubation outcome, i.e., appropriate work of breathing values may be associated with extubation success, while inappropriately increased values may be associated with failure.     

Carotid contrast-enhanced ultrasonography and multimodal imaging in a case of TIPIC syndrome

Transient perivascular inflammation of the carotid artery (TIPIC) syndrome, previously referred to as ‘carotidynia’, is an unclassified clinicoradiological entity associating atypical acute neck pain, eccentric perivascular infiltration on imaging and improvement of symptoms either spontaneously or with anti-inflammatory treatment. This case report presents a patient with TIPIC syndrome who underwent five different types of imaging modality, including contrast-enhanced ultrasonography (CEUS) of the carotids, and describes the CEUS appearances of TIPIC syndrome.     

DNA methylation studies on imprinted loci in a male monozygotic twin pair discordant for Beckwith–Wiedemann syndrome

Tierling S, Souren NY, Reither S, Zang KD, Meng‐Hentschel J, Leitner D, Oehl‐Jaschkowitz B, Walter J. DNA methylation studies on imprinted loci in a male monozygotic twin pair discordant for Beckwith–Wiedemann syndrome. Beckwith–Wiedemann syndrome (BWS) is one of the most prevalent congenital disorders predominantly caused by epigenetic alterations. Here we present an extensive case study of a monozygotic monochorionic male twin pair discordant for BWS. Our analysis allows to correlate BWS symptoms, like a protruding tongue, indented ears and transient neonatal hypoglycaemia, to an abnormal methylation at the KvDMR1. DNAs extracted from peripheral blood, skin fibroblasts, saliva and buccal swab of both twins, their sister and parents were analysed at 11 differentially methylated regions (DMRs) including all four relevant DMRs of the BWS region. The KvDMR1 was exclusively found to be hypomethylated in all cell types of the affected BWS twin, while the unaffected twin and the relatives showed normal methylation in fibroblasts, buccal swab and saliva DNA. Interestingly, the twins share a common blood‐specific hypomethylation phenotype most probably caused by a feto‐fetal transfusion between both twins. Because microsatellite analysis furthermore revealed a normal biparental karyotype for chromosome 11, our results point to an exclusive correlation of the observed BWS symptoms to locally restricted epimutations at the KvDMR1 of the maternal chromosome.     

Descriptive epidemiology of gastric adenocarcinoma in the State of Texas by ethnicity: Hispanic versus White non-Hispanic

Background

We aimed to evaluate the clinicopathological and demographic characteristics of gastric adenocarcinoma in Hispanics and compare these trends with those found in non-Hispanic Whites in Texas.

Methods

Records of patients with gastric adenocarcinoma found in the Texas Cancer Registry from 1995 to 2006 were reviewed. Four ethnic–geographic groups were formed: Hispanics residing in El Paso County (a county on the Texas–Mexico border), White non-Hispanics in El Paso County, Hispanics from the remaining counties of Texas combined, and White non-Hispanics from the remaining counties of Texas combined. Adjusted prevalence ratios (PRs) for the outcome of late stage at diagnosis were calculated.

Results

Of 9949 patients, 561 patients were El Paso County residents, of whom 83% were Hispanics. Among the four ethnic–geographic groups, the age-adjusted incidence was the highest in Hispanics in El Paso County (15.5 cases/100000). Tumor pathobiology varied by ethnicity. White non-Hispanics were more likely than Hispanics to have a proximal tumor and less likely to have a poorly differentiated or undifferentiated tumor. In El Paso County, patients in each of the eight age groups under 75?years compared to patients aged ≥85?years were significantly more likely to be at late stage (adjusted PRs 1.44–1.71).

Conclusion

The incidence of gastric adenocarcinoma is higher in Hispanics than in Whites in both El Paso County and the remaining portion of Texas. Hispanics have a higher grade of gastric adenocarcinoma. The prevalence of late stage at the time of diagnosis is higher in younger patients than in older patients.     

Pyodermatitis–pyostomatitis vegetans

A 43-year-old woman developed annular and pustular cutaneous lesions preceded by tiny yellow pustules coating the surface of the oral mucosa. The clinical, histological and immunopathological evidence clearly showed that the patient had pyodermatitis–pyostomatitis vegetans. It is suggested that this disease is a distinct entity which should be differentiated from pemphigus vegetans.     

Enhanced antigen uptake by dendritic cells induced by the B pentamer of the type II heat-labile enterotoxin LT-IIa requires engagement of TLR2

The potent mucosal adjuvant properties of the type II heat-labile enterotoxin LT-IIa of Escherichia coli are dependent upon binding of the B pentamer of the enterotoxin (LT-IIa-B₅) to ganglioside receptors on immunocompetent cells. To evaluate the immunomodulatory activities of LT-IIa-B₅, in vitro experiments employing bone marrow-derived dendritic cells (BMDC) were performed. Uptake of OVA-FITC, a model antigen (Ag), was enhanced by treatment of BMDC with LT-IIa-B5, but not by treatment of cells with the B pentamer of cholera toxin (CTB). Expression of co-stimulatory molecules (CD40, CD80, CD86, and MHC-II) and cytokines (IL-12p40, TNF-α, and IFN-γ) was increased in BMDC treated with LT-IIa-B₅. The capacity of LT-IIa-B₅ to enhance Ag uptake and to induce expression of co-stimulatory receptors and cytokines by BMDC was dependent upon expression of TLR2 by the cell. Increased Ag uptake induced by LT-IIa-B₅ was correlated with increased Ag-specific proliferation of CD4⁺ T cells in an in vitro syngeneic DO11.10 CD4⁺ T cell proliferation assay. These experiments confirm that LT-IIa-B₅ exhibits potent immunomodulatory properties which may be exploitable as a non-toxic mucosal adjuvant.