Mutant clones in normal epithelium outcompete and eliminate emerging tumours.

Human epithelial tissues accumulate cancer-driver mutations with age1-9, yet tumour formation remains rare. The positive selection of these mutations suggests that they alter the behaviour and fitness of proliferating cells10-12. Thus, normal adult tissues become a patchwork of mutant clones competing for space and survival, with the fittest clones expanding by eliminating their less competitive neighbours11-14. However, little is known about how such dynamic competition in normal epithelia influences early tumorigenesis. Here we show that the majority of newly formed oesophageal tumours are eliminated through competition with mutant clones in the adjacent normal epithelium. We followed the fate of nascent, microscopic, pre-malignant tumours in a mouse model of oesophageal carcinogenesis and found that most were rapidly lost with no indication of tumour cell death, decreased proliferation or an anti-tumour immune response. However, deep sequencing of ten-day-old and one-year-old tumours showed evidence of selection on the surviving neoplasms. Induction of highly competitive clones in transgenic mice increased early tumour removal, whereas pharmacological inhibition of clonal competition reduced tumour loss. These results support a model in which survival of early neoplasms depends on their competitive fitness relative to that of mutant clones in the surrounding normal tissue. Mutant clones in normal epithelium have an unexpected anti-tumorigenic role in purging early tumours through cell competition, thereby preserving tissue integrity.

Functional imaging of stress urinary incontinence.

Stress urinary incontinence (SUI) is defined as an involuntary loss of urine during increases in intraabdominal pressure such as coughing or laughing. It is often a consequence of weakness of the pelvic floor. Treatment of SUI consists of pelvic floor muscle training with EMG-biofeedback (PFMT) or contraction-exercises, with voluntary pelvic contractions in order to strengthen the pelvic floor. We investigated neuroplastic changes comparing PFMT with EMG-biofeedback before and after training in ten female patients with SUI using event-related functional Magnetic Resonance Imaging (fMRI). After a 12-week training a more focused activation in the primary motor and somatosensory cortical representation sites of the lower urogenital tract was found. In addition, reductions in brain activation in the insula, right frontal operculum and the anterior cingulate cortex suggest changes in emotional arousal in micturition after treatment. These changes are related to clinical improvement documented by decreased number of incontinence episodes and increased EMG-activity of the pelvic floor muscles after training. The changes in EMG-activity were correlated with heightened BOLD responses in the primary motor and primary sensory cortical representation sites of the lower urogenital tract.

A portable forced oscillation device for respiratory home monitoring.

The increase in the prevalence of chronic respiratory diseases has resulted in a rise in health services provided at home. The forced oscillation technique (FOT) proves to be a useful tool when it is desired to assess lung function noninvasively, and particularly for patients in whom spirometry cannot be applied. As no portable FOT device is currently available, the aim of this study was to design and test a portable FOT system for ambulatory and home care applications. The system devised is based on a microprocessor, which allows online computation of respiratory resistance (Rrs) and reactance (Xrs) and reliability indices. The portable device was compared with a conventional FOT system by using signals from 14 patients with chronic respiratory disease. This device has the same computation capabilities and flexibility as conventional FOT systems and meets the requirements for home application. Rrs (14.2 +/- 6.0 cmH2O x s x L(-1), mean +/- SD) and Xrs (-5.3 +/- 2.7 cmH2O x s x L(-1)) measured at 5 Hz by the portable system virtually coincided with those computed with the reference conventional FOT system: mean differences +/-SD were 0.074 +/- 0.025 and 0.005 +/- 0.009 cmH2O x s x L(-1), respectively. This portable forced oscillation technique device could be a useful tool for monitoring respiratory mechanics in ambulatory and home care applications.

Vesicocutaneous fistula 23 years after hip arthroplasty. A case report.

Vesicocutaneous fistula after total hip replacement is a very rare but severe complication, which can appear months or years after operation. Intrapelvic cement (methylmethacrilate) spilling, loosening and dislocation of the prosthesis and infection are believed to be the cause of fistula formation. Only 4 cases of this kind of fistula have been reported in the literature. A new case of vesicocutaneous fistula is presented. The fistula developed 23 years after arthroplasty mainly because of hip-joint infection. Urinary tract symptoms caused by urinary infection appeared only few months earlier.

Morphometric analysis of the fibroadipose tissue of the female pelvis.

PURPOSE: The structure of the retroperitoneal connective tissue of the female pelvis was evaluated to determine whether its spatial arrangement may have a role in supporting the pelvic viscera. MATERIALS AND METHODS: After in situ formalin fixation the pelvic viscera with the surrounding connective tissue were removed together with the pelvic floor from 18 female cadavers 48 to 68 years old. Serial macrosections of the bladder base, cervix, lower rectum and pelvic floor complex, cut in coronal (4 cases) and horizontal (10 cases) planes, were stained with azan-Mallory, and the remaining 4 were cut in the horizontal plane and plastinated using von Hagens E12 technique. Morphometry of the retroperitoneal connective tissue was performed using a computerized system for image analysis connected through a black and white television camera to an optic microscope. The diameters of the adipose lobules and density of the connective tissue were evaluated in the proximity of the visceral adventitia and the parietal pelvic fascia, respectively. RESULTS: The retroperitoneal connective tissue of the female pelvis consists of varying amounts of adipose tissue divided into small lobules by thin connective laminae. These laminae are connected to the visceral and parietal layers of the pelvic fascia, and are closely connected to the vascular and nervous bundle sheaths crossing the pelvis. At the level of the sacrouterine and cardinal ligaments we were unable to find any connective ligamentous structure. Only an areolar tissue was seen, which after removal of the lipids demonstrated a fibrillar structure. The mean area of the adipose lobules was smaller (average of 1.41 mm.2) near the viscera with respect to the lateral retroperitoneal connective tissue (average of 1.73 mm.2) due to greater ramification of the connective laminae. CONCLUSIONS: In the absence of real connective ligaments the retroperitoneal connective tissue forms a 3-dimensional network of thin connective laminae that are connected to the visceral adventitia, parietal layer of the pelvic fascia and neurovascular bundles crossing the pelvis. These connective laminae are bounding adipose lobules of different size (smaller near the viscera, larger at the periphery). Overall, the retroperitoneal connective tissue constitutes an anatomical structure that, beyond the functional limits of any individual ligament, may have supporting properties.