Prevalence of Renal Neoplasia in Autosomal Dominant Polycystic Kidney Disease: Systematic Review and Meta-analysis.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited condition, however its relationship with renal cell carcinoma (RCC) remains unclear. This paper aims to establish the prevalence of RCC and its subtypes amongst ADPKD patients. METHODS: A database search was conducted to retrieve studies reporting RCC occurrence within ADPKD patients until July 2023. Key outcomes included number and subtype of RCC cases, and number of RCCs presenting incidentally. A random-effects meta-analysis was performed. RESULTS: Our search yielded 569 articles, 16 met the inclusion criteria. Nephrectomy specimens from 1,147 ADPKD patients were identified. Of studies reporting per-kidney results (n = 13), 73 RCCs were detected amongst 1,493 kidneys, equating to a per-kidney prevalence of 4.3% (95% CI, 3.1 to 5.7, I2 = 15.7%). 75 ADPKD patients were found to have RCC (75/1147), resulting in a per-person prevalence of 5.7% (95% CI, 3.7 to 7.9, I2 = 40.3%) (n = 16). As 7 patients had bilateral disease, 82 RCCs were detected in total. Of these, 39 were clear cell RCC, 35 were papillary and 8 were other. As such, papillary RCCs made up 41.1% (95% CI, 25.9 to 56.9, I2 = 18.1%) of detected cancers. The majority of RCCs were detected incidentally (72.5% [95% CI, 43.7 to 95.1, I2 = 66.9%]). CONCLUSION: ADPKD appears to be associated with the papillary RCC subtype. The clinical implications of these findings are unclear, however may become apparent as outcomes and life expectancy amongst APDKD patients improve.

The provision of general surgery in rural Australia: a narrative review.

Rural surgery is most commonly provided by general surgeons to the 29% of people (7 million) living in rural Australia. The provision of rural general surgery to enable equitable and safe surgical care for rural Australians is a multifaceted issue concerning recruitment, training, retention, surgical procedures and surgical outcomes. Sustaining the rural general surgical workforce will be dependent upon growing an increased number of resident rural general surgeons, as well as changed models of care, with a need for ongoing review to track the outcomes of these changes. To increase recruitment, rural general surgical training must improve to be less stressful for trainees and to be incorporated alongside a rural-facing generalist curriculum. Rural general surgical outcomes (excluding some oncology conditions) achieve comparable results to metropolitan centres. Access to, and outcomes of, surgical oncology services continues to be inequitable for rural Australians and should be a major focus for improved service delivery.

Creating a sustainable rural general surgery workforce: what enables fellows to return as rural general surgeons?

INTRODUCTION: In the context of shortfalls in rural general surgeon supply, this research aims to explore why rural general surgical Fellows returned and remained after fellowship at a single rural centre in Victoria, Australia. Fellowship positions post achievement of Fellowship of the Australasian College of Surgeons are traditionally not funded by government because they currently fall outside the accredited rural training post funding provided by the federal government. This article aims to explore if fellowship positions can be an important part in sustaining the rural general surgery workforce. METHODS: Semi-structured interviews were conducted with nine former general surgery Fellows from a single rural Australian institution. Interviews were recorded, transcribed, coded and themed to undertake analysis according to thematic analysis. RESULTS: This research demonstrates that consultant rural general surgeons can be recruited from a fellowship year when emphasis is placed on: (1) creating a positive workplace culture with safe working hours, (2) ensuring diversification of the general surgical case mix, (3) facilitating opportunities for schooling and work for the surgeon's family, and (4) preferentially selecting for those who identify as rural general surgeons. Rural towns can effectively recruit general surgeons when families are supported with career and school opportunities, and the newly qualified surgeon can initially commit to a 12-month position so that opportunities can be assessed by the entire family unit. Fellowship positions (post completion of general surgical training) allow young surgeons to 'try before they buy' prior to moving to a rural area. CONCLUSION: Ensuring a sustainable general surgical workforce in a rural community requires employee and surgical leadership to ensure a collaborative and progressive culture, which offers work diversity, supports the family lifestyle and petitions for selecting those who embody the rural general surgeon identity. Post-fellowship positions can enable young general surgeons to have exposure to the realities of a rural lifestyle, which is likely to have a positive effect on recruitment. Due to the return investment of the fellowship program, we propose that the federal government should look at funding post-fellowship positions to improve rural recruitment.

Rural general surgeon confidence with managing vascular emergencies: A national survey.

OBJECTIVE(S): Life and limb threatening vascular emergencies often present to rural hospitals where only general surgery services are available. It is known that Australian rural general surgical centres encounter 10-20 emergency vascular surgery procedures annually. This study aimed to assess rural general surgeons' confidence managing emergent vascular procedures. SETTING, PARTICIPANTS AND DESIGN: A survey was distributed to Australian rural general surgeons to determine their confidence (Yes/No) in performing emergent vascular procedures including limb revascularisation, revising arterio-venous (AV) fistulas, open repair of ruptured abdominal aortic aneurysm (AAA), superior mesenteric artery (SMA)/coeliac embolectomy, limb embolectomy, vascular access catheter insertion and limb amputation (digit, forefoot, below knee and above knee). Confidence level was compared with surgeon demographics and training. Variables were compared using univariate logistic regression. RESULTS: Sixteen per cent (67/410) of all Australian rural general surgeons responded to the survey. Increased age, years since fellowship and training prior to 1995 (when separation of Australian vascular and general surgery occurred) were associated with greater confidence in limb revascularisation, revising AV fistulas, open repair of ruptured AAA, SMA/coeliac embolectomy, and limb embolectomy (p < 0.05). Surgeons who completed >6 months of vascular surgery training were more comfortable with SMA/coeliac embolectomy (49% vs. 17%, p = 0.01) and limb embolectomy (59% vs. 28%, p = 0.02). Confidence in performing limb amputation was similar across surgeon demographics and training (p > 0.05). CONCLUSION: Recently graduated rural general surgeons do not feel confident in managing vascular emergencies. Additional vascular surgery training should be considered as part of general surgical training and rural general surgical fellowships.

Safety and effectiveness of a novel home-use therapeutic ultrasound device for the treatment of vaginal dryness in postmenopausal women: a pilot study.

To evaluate safety and effectiveness of therapeutic ultrasound for treatment of postmenopausal vaginal dryness. In a pilot study, postmenopausal women with self-reported vaginal dryness were randomized (1:1) to double-blind ultrasound treatment (n = 21) or sham (n = 21) for 12 weeks. Primary effectiveness endpoint was change from baseline to week 12 in Vaginal Assessment Scale symptoms (dryness, soreness, irritation, dyspareunia). Secondary effectiveness endpoint was scoring of clinician-reported Vaginal Health Index (elasticity, fluid, pH, mucosa, moisture). After 12 weeks, participants received open-label ultrasound treatment to 1 year. Safety endpoint was treatment-emergent adverse events. In the modified intent-to-treat population, women showed (mean ± standard error) reduction in Vaginal Assessment Scale with ultrasound treatment versus sham (n = 15, −0.5 ± 0.2 vs n = 15, −0.4 ± 0.3; P = 0.9) and improved Vaginal Health Index (n = 9, 2.7 ± 0.9 vs n = 9, 0.6 ± 1.4; P = 0.3). In the per-protocol analysis population, ultrasound treatment (n = 9) versus sham (n = 8) significantly reduced symptoms score (−0.6 ± 0.3 vs −0.0 ± 0.4; P = 0.05) and significantly improved Vaginal Health Index (2.7 ± 0.9 vs −0.4 ± 1.2; P = 0.03). Improvement in effectiveness endpoints were seen at 1 year compared with baseline. There were no differences in treatment-emergent adverse events between ultrasound treatment versus sham and no serious adverse events. Home-use ultrasound was safe and effective for treating vaginal dryness after 12 weeks. Effectiveness was maintained to 1 year. Therapeutic ultrasound could offer a new, nonhormonal treatment option for postmenopausal women with vulvovaginal atrophy.

Australian trends in the treatment of pelvic organ prolapse in the non-mesh era.

BACKGROUND: To assess the contemporary trends in the types and incidence of pelvic organ prolapse (POP) surgery in Australia after the removal of transvaginal mesh from the Australian market. METHODS: This was a retrospective Australian cohort study utilizing three large Governmental databases covering all private and public POP procedures in Australia. All females ≥25 years old undergoing POP procedures between 2005 and 2021 were included. RESULTS: From 2005-2006 to 2020-2021 there have been a total of 408 881 POP procedures in Australia. The total number of procedures peaked in 2005-2006 at 537.8 procedures per 100 000 age-standardized female population, decreasing by an average of 3.5% per year to 329.0 procedures per 100 000 in 2018-2019, an overall 38.8% decrease (P < 0.001). A sudden growth in private operative procedures was noted between 2019-2020 and 2020-2021, from 218.2 to 268.6 procedures per 100 000 population, a 23.1% increase (P < 0.001). Laparoscopic and abdominal POP repair has seen a 115.8% increase from 13.7 procedures to 29.6 per 100 000 between 2005-2006 and 2020-2021. Over the last 15 years, the most common age group to undergo a procedure has changed from the 55 to 64 years demographic to a later decade of 65 to 74 years. CONCLUSION: Over the last 15 years, the total number of POP procedures performed has significantly decreased. There has however been a recent rise in interventions seen in the private sector and the utilization of laparoscopic or abdominal POP repair has increased, which has implications for procedural credentialing to ensure patient safety.

Colorectal surgical management of colitis induced by vasculitis in the absence of inflammatory bowel disease: a case report and literature review.

Colitis caused by vasculitis is a rare and poorly understood pathology. Little evidence exists on its clinical presentation, path to diagnosis, and surgical management. In this report, we present a case report and literature review. A healthy 20-year-old male patient presented with hemorrhagic colitis requiring total colectomy with end ileostomy. Pathological examination showed pancolitis with multiple ulcers, transmural inflammation, hemorrhage, and microvascular thrombosis. Extensive serological testing revealed elevated cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA) and eosinophilia, leading to a diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) and vasculitis-induced colitis. A literature review was subsequently conducted. Nineteen studies were found documenting vasculitis-induced colitis in the absence of inflammatory bowel disease (IBD). Systemic signs of vasculitis, hemorrhagic colitis, and progression to fulminant colitis were present. Of all patients, 40.0% required colorectal surgery and 62.5% of those patients received a stoma; 25% underwent emergency surgery following failed immunosuppression. All cases relied on clinical correlation with serology and/or histopathology to reach a final diagnosis. We report a case of vasculitis-induced colitis caused by c-ANCA-positive EGPA. The review shows that vasculitis-induced colitis without IBD is an important differential that clinicians should be aware of in patients presenting with colitis.

What a mesh! An Australian experience using national female continence surgery trends over 20 years.

PURPOSE: To review the evolution of female continence surgical practice in Australia over the last 20 years and observe whether vaginal mesh controversies impacted these trends. MATERIALS AND METHODS: From January 2000 to December 2019, medicare benefit schedule codes for female continence procedures were identified and extracted for: mesh sling, fascial sling, bulking agent, female urethral prosthesis, colposuspension, and removal of sling. Population-adjusted incidences per 100,000 persons were calculated using publicly available demographic data. Three discrete phases were defined over the study time frame for analysis: 2000-2006; 2006-2017, and 2017-2019. Interrupted time-series analyses were conducted to assess for impact on incidence at 2006 and 2017. RESULTS: There were 119,832 continence procedures performed in Australia from 2000 to 2019, with the mid-urethral sling (MUS) the most common (72%). The majority of mesh (n = 63,668, 73%) and fascial sling (n = 1864, 70%) procedures were in women aged < 65 years. Rates of mesh-related procedures steeply declined after 2017 (initial change: -21 cases per 100,000; subsequent rate change: -12 per 100,000, p < 0.001). Non-mesh related/bulking agents increased from + 0.34 during 2006-2017 to + 2.1 per 100,000 after 2017 (p < 0.001). No significant change in mesh extraction was observed over 2006-2017 (+ 0.06 per 100,000, p = 0.192). There was a significant increase in mesh extraction procedures after 2017 (0.83 per 100,000, p < 0.001). CONCLUSION: Worldwide, controversy surrounding vaginal mesh had a significant impact on Australian continence surgery trends. The most standout trends were observed after the 2017 Australian class-action lawsuit and Senate Inquiry.

Stress urinary incontinence in the mesh complication era: current Australian trends.

OBJECTIVES: To examine available data relating to the surgical management of stress urinary incontinence (SUI) in Australia before, during and after a well-publicized Senate Inquiry into transvaginal mesh use and to consider outcomes in the context of global guideline changes. PATIENTS AND METHODS: The annual number of surgical procedures for the management of SUI by procedure type and age group for the years 2008/2009-2017/2018 was obtained from the Australian Government Department of Human Services database using Medicare Benefits Schedule item numbers. The data extracted were limited to women aged 25 years and older. These data were used to calculate age-specific and age-standardized rates, so as to accurately analyse trends in the usage of different procedures. Hospital Episode Statistics for mid-urethral sling (MUS) insertions were obtained for England's National Health Service from the Health and Social Care Information Centre for the years 2008/2009-2016/2017. These data were also used to calculate annual age-standardized rates for comparison purposes. RESULTS: Rates declined for most SUI procedures over time (MUS, colposuspension, fascial slings) except for urethral bulking agents. The absolute number of MUSs implanted in 2008/2009 was 5729, which decreased to 3127 in the 2017/2018 financial year. Over the decade, the annual rate for MUS implantation per 100 000 population halved from 78 to 36. Over this same period, the rate of usage of bulking agents doubled, although represented a low volume of procedures (overall numbers increased from 304 to 698, representing an increase from four to eight procedures per 100 000 population). The age-specific peak rate for MUS and Burch colposuspension changed over the decade from 55-64 years to 65-74 years, suggesting that women are deferring surgical treatment until later in life. Over the last decade, the total number of surgical procedures performed in Australia to treat SUI has decreased markedly from 6812 to 4279. This represents a decrease in the annual rate per 100 000 population from 93 to 49. CONCLUSIONS: There are clear changes evident for SUI management in the past decade in Australia, including an overall decline in operative numbers, which correlate with international advisory notifications and local investigations. The results of the Australian Senate inquiry, including removal of single-incision mini-slings, greater availability of patient resources, and greater regulation of SUI procedures, will probably have ongoing effects. Surgeons need to ensure that sufficient training and patient education continue in order to maintain appropriate access to treatment of SUI in the future.

Quantifying the Effect of Location Matching on Accuracy of Multiparametric Magnetic Resonance Imaging Prior to Prostate Biopsy-A Multicentre Study.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) has shown promise to improve detection of prostate cancer over conventional methods. However, most studies do not describe whether the location of mpMRI lesions match that of cancer found at biopsy, which may lead to an overestimation of accuracy. OBJECTIVE: To quantitate the effect of mapping locations of mpMRI lesions to locations of positive biopsy cores on the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of mpMRI. DESIGN SETTING AND PARTICIPANT: We retrospectively identified patients having mpMRI of the prostate preceding prostate biopsy at three centres from 2013 to 2016. Men with targetable lesions on imaging underwent directed biopsy in addition to systematic biopsy. We correlated locations of positive mpMRI lesions with those of positive biopsy cores, defining a match when both were in the same sector of the prostate. We defined positive mpMRI as Prostate Imaging Reporting and Data System (PI-RADS) score ≥4 and significant cancer at biopsy as grade group ≥2. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Sensitivity, specificity, PPV, and NPV were calculated with and without location matching. RESULTS AND LIMITATIONS: Of 446 patients, 247 (55.4%) had positive mpMRI and 232 (52.0%) had significant cancer at biopsy. Sensitivity and NPV for detecting significant cancer with location matching (both 63.4%) were decreased compared with those without location matching (77.6% and 73.9%, respectively). Of the 85 significant cancers not detected by mpMRI, most were of grade group 2 (64.7%, 55/85). CONCLUSIONS: We report a 10-15% decrease in sensitivity and NPV when location matching was used to detect significant prostate cancer by mpMRI. False negative mpMRI remains an issue, highlighting the continued need for biopsy and for improving the standards around imaging quality and reporting. PATIENT SUMMARY: The true accuracy of multiparametric magnetic resonance imaging (mpMRI) must be determined to interpret results and better counsel patients. We mapped the location of positive mpMRI lesions to where cancer was found at biopsy and found, when compared with matching to cancer anywhere in the prostate, that the accuracy of mpMRI decreased by 10-15%.

Making surgery safer through adequate communication with the stakeholders: vaginal slings.

PURPOSE: In this review, we explore the evidence behind mid-urethral sling (MUS) surgery, review the rising reports of complications and the subsequent US Food and Drug Administration (FDA) and society statements, and evaluate risk perception and communication with patients, doctors, governing bodies, manufacturers and insurance companies. Our aim was to explore the pitfalls in communication that may be contributing to the decline in MUS use, and develop strategies to make MUS surgery safer. METHODS: We searched the English language literature using PubMed for articles related to the management of stress urinary incontinence (SUI), MUS, safety and monitoring of transvaginal mesh (TVM), and reviewed all online FDA publications and international position statements regarding MUS for SUI. RESULTS: Polypropylene mesh has been used in MUS since the 1990s, with robust evidence to support its use. There has been a decline in the use of MUS ever since the FDA notifications. In response to the controversy surrounding TVM, position statements have been released portending the safety of, and advocating for the continued use of, MUS for the management of SUI. CONCLUSIONS: MUS is a viable, effective and safe treatment for SUI management. Physicians should obtain and document informed consent, be adequately trained, and monitor and report their outcomes using registries. With publication of registry results and ongoing health advocacy, the perception of the safety of MUS can improve and MUS can still be offered as a treatment option for SUI.

Evaluation of the accuracy of multiparametric MRI for predicting prostate cancer pathology and tumour staging in the real world: an multicentre study.

OBJECTIVES: To assess the accuracy of multiparametric magnetic resonance imaging (mpMRI) for the detection of significant prostate cancer in men undergoing radical prostatectomy (RP) in an Australian multicentre setting, and to assess concordance between mpMRI and RP for local tumour staging and index lesion locations. PATIENTS AND METHODS: Men who underwent mpMRI within 12 months of RP between January 2013 and August 2016 at three Australian sites were included (Central Coast, NSW, St Vincents Hospital, Melbourne, Vic., and Bendigo Hospital, Vic.). The results of mpMRI were compared with the final RP specimen to analyse the performance of mpMRI for significant prostate cancer detection, index lesion localization, prediction of T3 disease and lymph node metastasis. A comparison between mpMRI cases performed using the technical and reporting specifications of Prostate Imaging Reporting and Data System (PI-RADS) version 1 and version 2 was also performed. Data analysis was performed using spss 24.0. RESULTS: A total of 235 cases were included for analysis. mpMRI PI-RADS score ≥3 had a 91% sensitivity and 95% positive predictive value (PPV) for significant prostate cancer at RP. The overall concordance between index lesion location on mpMRI and RP specimen was 75%. The sensitivity for predication of significant prostate cancer was higher in the PI-RADS version 2 cases compared with PI-RADS version 1 (87-99%; P = 0.005). Index lesion concordance was higher in the PI-RADS version 2 group (68% vs 91%; P = 0.002). mpMRI had a 38% sensitivity, 95% specificity, 90% PPV and 57% negative predictive value for extraprostatic disease. Sensitivity for prediction of T3 disease improved from 30% to 62% (P = 0.008) with PI-RADS version 2. CONCLUSIONS: In patients undergoing RP, an abnormal mpMRI is highly predictive (95% PPV) of significant prostate cancer, with an index lesion concordance of 75%. There has been a significant improvement in accuracy after the adoption of PI-RADS version 2 technical specifications and reporting criteria; however; further study is required to determine if this is attributable to improved experience with mpMRI or changes in the PI-RADS system.

Position statement: a clinical approach to the management of adult non-neurogenic overactive bladder.

INTRODUCTION: Overactive bladder (OAB) is a highly prevalent medical condition that has an adverse impact on various health-related quality-of-life domains, including a significant psychosocial and financial burden. This position statement, formulated by members of the Urological Society of Australia and New Zealand and the UroGynaecological Society of Australasia, summarises the current recommendations for clinical diagnosis and treatment strategies in patients with non-neurogenic OAB, and guides clinicians in the decision-making process for managing the condition using evidence-based medicine. Main recommendations: Diagnosis and initial management should be based on thorough clinical history, examination and basic investigations to exclude underlying treatable causes such as urinary tract infection and urological malignancy. Initial treatment strategies for OAB involve conservative management with behavioural modification and bladder retraining. Second-line management involves medical therapy using anticholinergic or ß3 agonist drugs provided there is adequate assessment of bladder emptying. If medical therapy is unsuccessful, further investigations with urodynamic studies and cystourethroscopy are recommended to guide further treatment. Intravesical botulinum toxin and sacral neuromodulation should be considered in medical refractory OAB. Changes in management as a result of this statement: OAB is a constellation of urinary symptoms and is a chronic condition with a low likelihood of cure; managing patient expectations is essential because OAB is challenging to treat. At present, the exact pathogenesis of OAB remains unclear and it is likely that there are multiple factors involved in this disease complex. Current medical treatment remains far from ideal, although minimally invasive surgery can be effective. Further research into the pathophysiology of this common condition will hopefully guide future developments in disease management.

The dilemma of distance: patients with kidney cancer from regional Australia present at a more advanced stage.

OBJECTIVE: To determine whether patients from regional areas undergoing surgery for kidney cancer present with more advanced disease as a result of geographic isolation. PATIENTS AND METHODS: Retrospective analysis of 221 patients undergoing surgery for renal cell carcinoma (RCC) from January 2004 to June 2012, from both a metropolitan centre and a large inner regional hospital. Data was collected on age, gender, presentation (incidental or symptomatic), clinical stage and pathological features. The Australian Standard Geographical Classification-Remoteness Area (ASGC-RA) is a system developed to allow quantitative comparisons between metropolitan and rural Australia. A score was assigned to each patient based on their location of residence at the time of surgery: metropolitan, RA1; inner regional, RA2; outer regional, RA3. Statistical significance was specified as P < 0.05 on Pearson's chi-square tests. RESULTS: Patients in each ASGC-RA group did not differ significantly in age, sex or mode of presentation. Pathological T stage on presentation increased with increasing ASGC-RA and thus distance from tertiary centres (P = 0.004). The proportion of patients with ≥T3 disease rose from 30% of RA1 to 73% of RA3 patients (P = 0.016) treated at our tertiary centre. Similarly, our regional centre had a larger proportion of patients presenting with ≥T3 disease from RA3 (31% vs 5%, P = 0.003). When the 221 patients with RCC were analysed as a group, clinical T stage was significantly associated with ASGC-RA (P < 0.001), symptomatic presentation (P < 0.001), N stage (P < 0.001), M stage (P < 0.001) and Fuhrman grade (P < 0.001). CONCLUSIONS: Our data quantifies the detrimental effect of physical distance on the health outcomes of regional Australians with kidney cancer. Australia's unique geography and rural culture may preclude any attempts to centralise cancer care to specialised metropolitan units, as has occurred in other countries.

Mesenchymal-to-epithelial transition facilitates bladder cancer metastasis: role of fibroblast growth factor receptor-2.

Epithelial-to-mesenchymal transition (EMT) increases cell migration and invasion, and facilitates metastasis in multiple carcinoma types, but belies epithelial similarities between primary and secondary tumors. This study addresses the importance of mesenchymal-to-epithelial transition (MET) in the formation of clinically significant metastasis. The previously described bladder carcinoma TSU-Pr1 (T24) progression series of cell lines selected in vivo for increasing metastatic ability following systemic seeding was used in this study. It was found that the more metastatic sublines had acquired epithelial characteristics. Epithelial and mesenchymal phenotypes were confirmed in the TSU-Pr1 series by cytoskeletal and morphologic analysis, and by performance in a panel of in vitro assays. Metastatic ability was examined following inoculation at various sites. Epithelial characteristics associated with dramatically increased bone and soft tissue colonization after intracardiac or intratibial injection. In contrast, the more epithelial sublines showed decreased lung metastases following orthotopic inoculation, supporting the concept that EMT is important for the escape of tumor cells from the primary tumor. We confirmed the overexpression of the IIIc subtype of multiple fibroblast growth factor receptors (FGFR) through the TSU-Pr1 series, and targeted abrogation of FGFR2IIIc reversed the MET and associated functionality in this system and increased survival following in vivo inoculation in severe combined immunodeficient mice. This model is the first to specifically model steps of the latter part of the metastatic cascade in isogenic cell lines, and confirms the suspected role of MET in secondary tumor growth.