Benefit of Adjuvant Chemotherapy and Pelvic Lymph Node Dissection in pT3 and Node Positive Bladder Cancer Patients Treated with Radical Cystectomy.

Background: Benefits of adjuvant chemotherapy (AC) and extent of pelvic lymph node dissection (PLND) in radical cystectomy (RC) are debated. Results from randomized trials are still expected. Objective: To analyze the effects of AC and PLND in two academic centers with opposite policies regarding their use. Methods: 581 bladder cancer patients who underwent RC without neoadjuvant chemotherapy, from Toronto (University Health Network), Canada, and Turku University Hospital, Finland were included. Disease specific survival (DSS) and failure patterns were assessed. Results: Centers differed in PLND rate (93% and 36% in Toronto and Turku respectively, p <  0.001), PLND extent (≥10 removed nodes, 58% vs. 8%, p <  0.001) and AC rate (21% vs. 2%, p <  0.001). Survival between centers among pT≤1 or pT4 patients was similar. pT3 patients in Toronto had an improved 10 year DSS (43% vs. 22%, p = 0.025). Distant failures were less common after AC (HR 0.56, 95%  CI 0.33-0.98, p <  0.042). In node positive (N+) patients, mortality was significantly higher in Turku (HR 2.19, 95%  CI 1.44-3.34, p <  0.001) and lower in patients receiving AC (HR 0.60, 95%  CI 0.37-0.99, p = 0.044). 41% DSS at 10 years was observed in N+ Toronto patients. Limitations included the non-randomized retrospective design and absence of propensity score analysis. Conclusion: Combining AC and PLND to RC is associated with improved survival in pT3 and N+ patients. PLND did not affect survival independently but helps in selecting patients for AC. Our data adds to the growing body of evidence supporting the usefulness of AC in addition to PLND in high risk patients operated by cystectomy.

Role of ultrasensitive prostate-specific antigen in the follow-up of prostate cancer after radical prostatectomy.

OBJECTIVE: Prostate-specific antigen (PSA) is an important tool in the follow-up of prostate cancer after radical prostatectomy (RP). However, the relevance of ultrasensitive PSA (uPSA) after RP is not well defined. The aim of this study was to investigate the value of uPSA in follow-up after RP and to determine whether ultrasensitive PSA doubling time (uDT) correlates with traditional PSA doubling time (tDT). PATIENTS AND METHODS: In total, 604 consecutive patients undergoing open RP and pelvic lymphadenectomy between 2004 and 2008 (minimum 5y of follow-up) were studied. To evaluate the postsurgical uPSA level, scatter plot statistics were used. To correlate uDT and tDT in patients with a biochemical recurrence (PSA ≥0.2ng/ml), at least 2 uPSA and 2 PSA measurements without salvage treatment were required and a weighted Cohen kappa statistic and receiver operating characteristic curve were used to test agreement across the categories. RESULTS: There were 229 patients without biochemical recurrence who did not have 3 rising PSA values after nadir within ultrasensitive area. Their highest uPSA value was between 0.003 and 0.1ng/ml. In 97.4% of patients, the highest uPSA value was less than 0.03ng/ml, and in 89% of these patients, the values were less than 0.02ng/ml. The median uDT and tDT were 10.2 and 11.4 months, respectively. The weighted Cohen kappa statistic between these 2 groups was 0.30 (95% CI:-0.09 to 0.50), demonstrating a poor agreement of PSA doubling time across categories. The predictive capability of uDT was tested with tDT <9 months. A receiver operating characteristic curve area under the curve value was 0.737 (95% CI:-0.577 to 0.897) demonstrating a fair agreement between the groups. CONCLUSIONS: uPSA values>0.03ng/ml seems to be valid and can be used in a clinical setting. There was a poor to fair agreement between tDT and uDT. The accuracy of uDT improves when it approaches the traditional PSA threshold of 0.1ng/ml. Also according to our results, there is no prognostic benefit of uDT calculation.

Lack of decorin expression by human bladder cancer cells offers new tools in the therapy of urothelial malignancies.

Decorin, a multifunctional small leucine-rich extracellular matrix proteoglycan, has been shown to possess potent antitumour activity. However, there is some uncertainty whether different cancer cells express decorin in addition to non-malignant stromal cells. In this study we clarified decorin expression by human bladder cancer cells both in vivo and in vitro. In addition, the effect of adenovirus-mediated decorin expression on human bladder cancer cells in vitro was examined. We first demonstrated using the publicly available GeneSapiens databank that decorin gene expression is present in both normal and malignant human bladder tissues. However, when we applied in situ hybridization with digoxigenin-labeled RNA probes for decorin on human bladder carcinoma tissue samples derived from a large radical cystectomy patient cohort (n = 199), we unambiguously demonstrated that invasive and non-invasive bladder carcinoma cells completely lack decorin mRNA. The cancer cells were also negative for decorin immunoreactivity. Instead, decorin expression was localized solely to original non-malignant stromal areas of bladder tissue. In accordance with the aforementioned results, human bladder cancer cells in vitro were also negative for decorin expression as shown by RT-qPCR analyses. The lack of decorin expression by bladder cancer cells was shown not to be due to the methylation of the proximal promoter region of the decorin gene. When bladder cancer cells were transfected with a decorin adenoviral vector, their proliferation was significantly decreased. In conclusion, we have shown that human bladder cancer cells are totally devoid of decorin expression. We have also shown that adenovirus-mediated decorin gene transduction of human bladder cancer cell lines markedly inhibits their proliferation. Thus, decorin gene delivery offers new potential therapeutic tools in urothelial malignancies.

Prescribing of sick leave by surgeons: a survey based on hypothetical patient cases.

BACKGROUND: Physicians regard the tasks of sick-listing and work ability assessments problematic and among the most challenging duties in their practice. Few studies have analyzed sick leave prescribing practices, and the practices have been shown to vary among physicians. The aim of this study was to examine the prescribing of sick leave by surgeons and factors that affect these prescribing practices. METHODS: A questionnaire study with 19 hypothetical patient cases was conducted among 338 Finnish surgeons. The effects of both physician-related and local structural background variables on sick leave prescribing were studied using univariate and multiple linear regression models. The economic consequences of the variation in sick leave prescribing were estimated. RESULTS: The overall number of days of sick leave prescribed for the entire group of 19 patient cases averaged 281.4 days (range = 134-490 days). With the same diagnosis, surgeons prescribed more days of sick leave for patients who do physical work than for those who work in an office. Older surgeons with more working experience and those working in smaller municipalities or in smaller hospitals prescribed longer sick leave than others. Clinical specialists tended to prescribe longer sick leave than those still in specialty training. CONCLUSION: Structured education for surgeons on prescribing sick leave, together with defined guidelines, could produce more uniform practices and improve equality among patients.

Mannose reduces hyaluronan and leukocytes in wound granulation tissue and inhibits migration and hyaluronan-dependent monocyte binding.

Wound healing is a highly regulated process starting from coagulation and ending in tissue remodeling. The end result varies from perfectly restored tissue, such as in early fetal skin, to scars in adults. The balanced repair process is frequently disturbed by local or systemic factors, like infections and diabetes. A rapid increase of hyaluronan is an inherent feature of wounds and is associated with tissue swelling, epithelial and mesenchymal cell migration and proliferation, and induction of cytokine signaling. Hyaluronan extending from cell surface into structures called cables can trap leukocytes and platelets and change their functions. All these features of hyaluronan modulate inflammation. The present data show that mannose, a recently described inhibitor of hyaluronan synthesis, inhibits dermal fibroblast invasion and prevents the enhanced leukocyte binding to hyaluronan that takes place in cells treated with an inflammatory mediator interleukin-1ß. Mannose also reduced hyaluronan in subcutaneous sponge granulation tissue, a model of skin wound, and suppressed its leukocyte recruitment and tissue growth. Mannose thus seems to suppress wounding-induced inflammation in skin by attenuating hyaluronan synthesis.

Loss of MUC2 expression predicts disease recurrence and poor outcome in colorectal carcinoma.

Clinical staging and histological grading after surgery have been the "gold standard" for predicting prognosis and planning for adjuvant therapy of colorectal cancer (CRC). With the recent development of molecular markers, it has become possible to characterize tumors at the molecular level. This is important for stage II and III CRCs, in which clinicopathological features do not accurately predict heterogeneity, e.g., in their tumor response to adjuvant therapy. In the present study, archival samples from 141 patients with stage I, II, III, or IV CRC treated during 1981-1990 at Turku University Hospital (Finland) were used (as microarray blocks) to analyze MUC2 expression by immunohistochemistry. Altogether, 49.7 % of all tumors were positive for MUC2. There was no significant correlation between MUC2 expression and age (P < 0.499), tumor invasion (P < 0.127), tumor staging (P < 0.470), histological grade (P < 0.706), lymph node involvement (P < 0.854), or tumor metastasis (P < 0.586). However, loss of MUC2 expression was significantly associated with disease recurrence (P < 0.031), tumor localization (P < 0.048), and with borderline significance with gender (P < 0.085). In univariate (Kaplan-Meier) survival analysis, positive MUC2 significantly predicted longer disease-free survival (DFS) and disease-specific survival (DSS) as well. However, in multivariate (Cox) survival analysis, MUC2 lost its power as an independent predictor of DFS and DSS. Our results implicate the value of MUC2 expression in predicting disease recurrence and long-term survival in CRC.

MMP-13 regulates growth of wound granulation tissue and modulates gene expression signatures involved in inflammation, proteolysis, and cell viability.

Proteinases play a pivotal role in wound healing by regulating cell-matrix interactions and availability of bioactive molecules. The role of matrix metalloproteinase-13 (MMP-13) in granulation tissue growth was studied in subcutaneously implanted viscose cellulose sponge in MMP-13 knockout (Mmp13(-/-)) and wild type (WT) mice. The tissue samples were harvested at time points day 7, 14 and 21 and subjected to histological analysis and gene expression profiling. Granulation tissue growth was significantly reduced (42%) at day 21 in Mmp13(-/-) mice. Granulation tissue in Mmp13(-/-) mice showed delayed organization of myofibroblasts, increased microvascular density at day 14, and virtual absence of large vessels at day 21. Gene expression profiling identified differentially expressed genes in Mmp13(-/-) mouse granulation tissue involved in biological functions including inflammatory response, angiogenesis, cellular movement, cellular growth and proliferation and proteolysis. Among genes linked to angiogenesis, Adamts4 and Npy were significantly upregulated in early granulation tissue in Mmp13(-/-) mice, and a set of genes involved in leukocyte motility including Il6 were systematically downregulated at day 14. The expression of Pdgfd was downregulated in Mmp13(-/-) granulation tissue in all time points. The expression of matrix metalloproteinases Mmp2, Mmp3, Mmp9 was also significantly downregulated in granulation tissue of Mmp13(-/-) mice compared to WT mice. Mmp13(-/-) mouse skin fibroblasts displayed altered cell morphology and impaired ability to contract collagen gel and decreased production of MMP-2. These results provide evidence for an important role for MMP-13 in wound healing by coordinating cellular activities important in the growth and maturation of granulation tissue, including myofibroblast function, inflammation, angiogenesis, and proteolysis.

Loss of E-cadherin expression predicts disease recurrence and shorter survival in colorectal carcinoma.

The traditional staging system is currently inadequate for identifying those patients with colorectal carcinoma (CRC) who carry a high risk for poor outcome. In this study, the expression of E-cadherin was evaluated in CRC to determine its correlation with clinico-pathological variables, and association with disease outcome in patients with long-term follow-up. The present series consisted of tissue samples obtained from 230 patients with stage I, II, III, or IV CRC treated during 1981-1990 at Turku University Hospital. Archival paraffin-embedded samples were used to build up tissue microarray blocks, and E-cadherin expression was assessed by immunohistochemistry using an automated staining system. Different grading systems were tested for expression of E-cadherin. Fifty-nine percent of all tumors were positive for E-Cadherin. There was no significant correlation between E-cadherin expression and gender (p < 0.83), localization (p < 0.45), tumor invasion (p < 0.32), or histologic grade (p < 0.41). However, loss of E-cadherin expression was significantly associated with older age (p < 0.03) and lymph node involvement (p < 0.02), and with borderline significance with advanced stage (p < 0.09) and tumor metastasis (p < 0.09). In univariate (Kaplan-Meier) survival analysis, positive E-cadherin significantly (p = 0.009) predicted longer disease-free survival (DFS), and the same was true with disease-specific survival (DSS) as well (p = 0.007). In multivariate (Cox) survival analysis, E-cadherin retained its significance as independent predictor of DFS (HR = 1.56; 95% CI 1.01-2.42, p = 0.043), but not DSS. A sub-group analysis revealed that E-cadherin expression also predicts DFS (p < 0.01) and DSS (p < 0.04) in stage II CRC. Our results implicate the usefulness of E-cadherin expression in predicting disease recurrence and long-term survival in CRC.

Upstaging of urothelial cancer at the time of radical cystectomy: factors associated with upstaging and its effect on outcome.

UNLABELLED: What's known on the subject? and What does the study add? The reported discordance between staging on transurethral bladder resection and on radical cystectomy pathology in the literature ranges from 20 to 80%.Correct staging in bladder cancer has direct implications for its management. The upstaging from organ-confined (OC) to non-organ-confined (nOC) disease has been reported in 40% of cases. Lymphovascular invasion (LVI) is a factor known to be associated with poor clinical outcome. Pathological upstaging was observed in our cohort in 40% of cases and most cases (80%) were upstaged from OC to nOC disease. During the study period the frequency of upstaging observed increased. We found LVI (hazard ratio [HR]= 5.07, 95% CI = 3.0-8.3, P < 0.001) and any histological variant variant (HR = 2.77, 95% CI = 1.6-4.8, P < 0.001) to be strong independent predictors of upstaging. Patients with clinical T2 bladder cancer found with upstaging at the time of radical cystectomy had a poorer outcome than patients with no upstaging. Identification of patients at high risk of upstaging at radical cystectomy is key to improving their management and outcome. OBJECTIVES: To analyse the details of bladder cancer (BC) staging in a large combined radical cystectomy (RC) database from two academic centres. To study rate and time trends, as well as risk factors for upstaging, especially clinical factors associated with staging errors after RC. PATIENTS AND METHODS: Characteristics of patients undergoing RC at University Health Network, Toronto, Canada (1992-2010) and University of Turku, Turku, Finland (1986-2005) were analysed. RESULTS: Among 602 patients undergoing RC, 306 (51%) had a discordance in clinical and pathological stages. Upstaging occurred in 240 (40%) patients and 192 (32%) patients were upstaged from organ-confined (OC) to non-organ-confined (nOC) disease. During the study period, upstaging became more common in both centres. In multivariate analyses, T2 disease at initial presentation (P= 0.001, odds ratio [OR]= 2.62, 95% confidence interval [CI]: 1.44-4.77), high grade disease (P= 0.01, OR = 2.85, 95% CI: 1.21-6.7), lymphovascular invasion (LVI) (P < 0.001, OR = 5.17, 95% CI: 3.48-7.68), female gender (P= 0.038, OR = 0.6, 95% CI: 0.38-0.97, and histological variants (P < 0.001, OR = 2.77, 95% CI: 1.6-4.8) were associated with a risk of upstaging from OC to nOC disease. Upstaged patients had worse survival rates than patients with correct staging. This was especially significant among patients with carcinoma invading bladder muscle before undergoing RC (16% vs 46% 10-year disease-specific mortality, P < 0.001). CONCLUSIONS: Upstaging is a common problem and unfortunately no improvements have been observed during the last two decades. LVI and the presence of histological variants are strong predictors of upstaging at the time of RC. Pathologists should be encouraged to report LVI and any histological variant at the time of TURBT.

Sex differences in bladder cancer outcomes among smokers with advanced bladder cancer.

OBJECTIVE: To study the effect of smoking on bladder cancer presentation and outcome in a large cystectomy population. PATIENTS AND METHODS: A database including 546 patients from the University Health Network (Toronto, Canada) and Turku University Hospital (Turku, Finland) was studied. In addition to the association of smoking with clinicopathological parameters, the effect of smoking on survival was analyzed. Categorical data were analyzed by the chi-squared test and numerical data were analyzed by Student's t-test. The Kaplan-Meier method, log-rank test and a proportional hazards model were used to estimate the effect of smoking on survival. RESULTS: In total, 352 patients (64%) were smokers and 194 (36%) were non-smokers. Smokers had more frequently advanced tumours and nodal metastasis. The 10-year disease-specific survival (DSS) was 52% vs 66% for smokers and non-smokers, respectively (P = 0.039). Smokers also had significantly worse overall survival (10-year overall survival 37% vs 62%; P = 0.015). Smoking affected significant DSS among men (P = 0.012), although no effect was observed among women. In a univariate model smoking was associated with a hazard ratio (HR) of 1.4 (95% confidence interval, CI, 1.0-1.9) for bladder cancer specific mortality and 1.4 (95% CI, 1.1-1.8) for overall mortality. In a multivariate model, smoking did not impact on DSS (HR, 1.1; 95% CI, 0.8-1.6; P = 0.41). In addition to advanced stage and nodal metastasis, female sex was an independent risk factor for DSS (HR, 1.6; 95% CI, 1.1-2.3; P = 0.007). CONCLUSIONS: Smokers appear to have worse outcomes after radical cystectomy for bladder cancer; however, it does not appear to be an independent prognostic factor for survival. Smoking affected survival only among men. Women had poorer survival but smoking was not a contributing factor to this.

[Update on current care guidelines: urinary tract infections]. / Käypä hoito -suosituksen päivitystiivistelmä. Virtsatieinfektiot.

This guideline is focused on the diagnostics and treatment of acute, recurrent and relapsing urinary tract infections in adults and children. Sexually transmitted diseases are not addressed, but must be considered in differential diagnostics. The resistance prevalence of the causative microbes and the ecological adverse effects of antimicrobial agents were considered important factors in selecting optimal therapeutic choices for the guideline. Diagnosis and management of cystitis in otherwise healthy women aged 18-65 years can be based on structured telephone interviews. Primary antimicrobiotic drugs are nitrofurantoin, pivmesillinam and trimetoprim for three days.

MMP-9 (gelatinase B) expression is associated with disease-free survival and disease-specific survival in colorectal cancer patients.

Extracellular matrix degradation is required for invasion and metastasis formation in colorectal carcinoma (CRC), therefore, we have examined matrix metalloproteinases MMP-9 expression in tumors from patients with CRC. The study comprises of 360 patients who underwent bowel resection for stage II, III, IV tumors. Paraffin-embedded CRC tissue samples were used for immunohistochemical staining. Negative MMP-9 expression levels correlated with longer survival time as evaluated by disease-free survival and disease-specific survival (p =.023, p =.006). In multivariate survival (Cox) analysis, MMP9 was a significant independent predictor of DFS (p =.014), but not of DSS, which was independently predicted by disease recurrence, stage and localization. The detection of MMP-9 expression may be valuable in finding patients who are at high risk of developing disease recurrence.

Twenty-year experience of radical cystectomy for bladder cancer in a medium-volume centre.

OBJECTIVE: To evaluate long-term survival after radical cystectomy (RC) for bladder cancer (BC) and to define risk factors for BC-specific death. MATERIAL AND METHODS: Patients having RC for BC with curative intent in Turku University Hospital 1986-2005 were assessed. Survival results were recorded and 10 risk factors for BC-specific death were analysed. RESULTS: In total, 248 patients with a median age of 64 years were included in the study. Sixty-four per cent of the tumours were intravesical and the lymph-node metastasis rate was 9%. Disease recurrence was observed in 90 patients (36%). Median time for local recurrence and distant metastasis after RC was 9 and 12 months, respectively. The mortality rate for both local recurrence and distant metastasis was 93%. Upper urinary tract and urethral recurrences were less common (3% and 5%, respectively) and occurred later (median time to recurrence 26 and 18 months, respectively). The 5-, 10-, and 15-year BC-specific survival was 69%, 67% and 66%, respectively. Extravesical tumour status, high tumour grade, positive node status and no history of intravesical therapy before RC were significant risk factors for BC-specific death. Other variables (neoadjuvant radiation, lymphadenectomy, age, time period, gender, smoking) did not affect the risk. CONCLUSIONS: The survival results are comparable with those of high-volume centres and demonstrate the possibility of excellent local control in all cases and a high rate of cure in tumours confined to the bladder. Extravesical tumour growth, high grade and lymph-node metastasis are the most important risk factors for BC-specific mortality.

Prognostic significance of matrix metalloproteinase-9 (MMP-9) in stage II colorectal carcinoma.

BACKGROUND: Approximately 30% of all colorectal cancer patients are diagnosed with stage II disease. Adjuvant therapy is not widely recommended. However, it is well-established that a subgroup of patients with stage II is at high risk for recurrence within their life time and should be considered for adjuvant chemotherapy. The present work was designed to assess the value of matrix metalloproteinase-9 (MMP-9) as a predictor of disease outcome in a series of 202 stage II colorectal cancer (CRC) patients with long-term follow-up. METHODS: The present study comprises a series of 202 patients who underwent bowel resection for stage II CRC at Turku University Hospital. Archival paraffin-embedded CRC tissue samples were used to prepare tissue microarray blocks for immunohistochemical staining with MMP-9 antibody. RESULTS: Forty-eight percent of all CRC samples were positive for MMP-9. There was no significant correlation between MMP-9 expression and age, depth of invasion, and lymph node status. However, MMP-9 expression was significantly related to histological grade (p = 0.03) and location of the tumor (p = 0.01), therefore, being lower in high-grade tumors and most intense in carcinomas of the descending colon and rectum. Tumors with high MMP-9 expression showed a higher recurrence rate than tumors with low expression (p = 0.02). MMP-9 negative tumors had a more favorable disease-free survival (DFS) than those expressing MMP-9 (p = 0.03). The same was true with disease-specific survival (DSS; p = 0.02) as well, high expression of MMP-9 being associated with shorter survival rates. In multivariate (Cox) survival analysis, MMP-9 expression proved to be an independent predictor of DFS, but not DSS, which was predicted by age and sex only. CONCLUSION: Quantification of MMP-9 expression seems to provide valuable prognostic information in stage II CRC, particularly, in selecting the patients at high risk for recurrent disease who might benefit from adjuvant therapy.

Protodynamic therapy for bladder cancer: in vitro results of a novel treatment concept.

OBJECTIVE: To present a novel treatment approach for urinary bladder cancer, protodynamic therapy, which comprises inhibition of cancer cell proliferation by intracellular acidification; cis-urocanic acid (cis-UCA) was investigated as a protodynamic drug in bladder cancer cell cultures and compared with conventional chemotherapeutic agents. MATERIALS AND METHODS: The moderately differentiated cell line 5637 and the poorly differentiated T24 cell line were exposed to cis-UCA for 0.25-2 h, and to epirubicin, doxorubicin, cisplatin and paclitaxel for 2 h, to simulate drug exposure on intravesical instillation. The combination of cis-UCA and chemotherapeutic agents was also studied. Cell viability was measured with a colorimetric assay. RESULTS: cis-UCA inhibited proliferation and suppressed the survival of cells at an extracellular pH pK(a2), as suggested by the protodynamic theory. cis-UCA caused dose-dependent, irreversible termination of cell proliferation. The number of viable surviving BC cells decreased by >85% with 2%cis-UCA (P < 0.001). Viable cells disappeared completely with 4% and 6%cis-UCA after a 2-h treatment, and by 90% with 6%cis-UCA within a 15-min exposure. These effects were associated with distinct morphological changes. The other drugs tested had a clearly lower effect on cell survival. Interestingly, when combined, cis-UCA markedly enhanced the cytotoxic effect of epirubicin. CONCLUSION: cis-UCA is a potent antiproliferative agent in bladder cancer cell cultures. As our previous non-clinical studies showed that cis-UCA is locally and systemically well tolerated, protodynamic therapy with cis-UCA is a promising intravesical treatment for bladder cancer.

Risk factors for mortality and morbidity related to radical cystectomy.

OBJECTIVES: To evaluate the risk factors for mortality and morbidity related to radical cystectomy (RC) in a medium-sized academic centre, and to analyse the rate and trends of perioperative morbidity and mortality, as although complications related RC to are lower in modern than historic series, RC is still associated with marked risks. PATIENTS AND METHODS: The study included 258 patients undergoing RC for bladder cancer in Turku University Hospital in 1986-2005. Basic patient characteristics and in-hospital, early (from hospital discharge to 3 months) and combined morbidity and mortality were analysed. Risk analysis included 16 risk factors for complications. Trends were analysed by comparing the two study decades (1986-1995 vs 1996-2005). RESULTS: The total complication rate was 34%, with minor and major complications in 26%, and 11% of patients, respectively. There were no significant changes in total morbidity, but the number of myocardial infarctions and atrial fibrillations decreased significantly (P = 0.045). Operative mortality was 2.7%, with an insignificant decrease (4.2% to 0.9%, P = 0.11) over time. Salvage RC, high American Society of Anesthesiologists (ASA) score (> or = 3), extensive blood loss (>3 L), a high number of transfusions (five or more), several comorbidities (two or more), age (> or = 65 vs <65 years), and extravesical tumours were significant risk factors for major complications. An ASA score of > or = 3 and five or more transfusions were the only factors associated with mortality. A high ASA score (odds ration 3.25, 95% confidence interval 1.08-9.74) and high number of transfusions (2.74, 1.05-7.15) were independent risk factors for major complications. CONCLUSION: Although RC is associated with acceptable morbidity, attention should be given to risk factors identified at the time of patient selection, and to meticulous haemostasis at the time of surgery. A predictable outcome comparable to that in high-volume centres is also possible in a medium-sized hospital.

VEGF-1 expression in colorectal cancer is associated with disease localization, stage, and long-term disease-specific survival.

BACKGROUND: Angiogenesis plays an important role in progression of colorectal carcinoma (CRC). Evidence from preclinical and clinical studies indicates that vascular endothelial growth factor (VEGF) is the predominant angiogenic factor in CRC. Indeed, VEGF is expressed in approximately 50% of CRCs, with minimal to no expression in normal colonic mucosa and adenomas. In this study, the expression of VEGF-1 was examined in stage I-IV CRCs to determine its clinicopathological correlates, and association with the response to treatment and disease outcome. PATIENTS AND METHODS: The present series consisted of tissue samples obtained from 360 patients with stage I, II, III, or IV CRC who had undergone large bowel resection during 1981-1990 at Turku University Hospital. Archival paraffin-embedded CRC tissue samples were used to build up tissue microarray (TMA) blocks and VEGF-1 expression was assessed immunohistochemically using an automated staining system. Three different grading systems were applied to evaluate the expression of VEGF-1. RESULTS: Seventy percent of patients with stage IV CRC had positive VEGF-1 expression, while 50% and 47%, respectively of patients with stage II and III CRC had positive VEGF-1 expression (p = 0.005). VEGF-1 expression in the left colon and rectum was significantly higher than that in the right colon (61% vs. 45%, respectively) (p = 0.006). Significant statistical correlation (p = 0.04) was found between VEGF-1 and 10-year disease-specific survival: patients who died of the disease more frequently had a VEGF-1-expressing tumour than did those who survived for 10 years. CONCLUSION: Quantification of VEGF-1 expression seems to provide valuable prognostic information in CRC, particularly in selecting those patients at high risk for disease progression who are likely to benefit from adjuvant therapy.

Laparoscopic sigmoid and rectal resection using an electrothermal bipolar vessel sealing device.

BACKGROUND: Laparoscopic colonic resection has gained popularity as a method to treat colonic diseases. The electrothermal bipolar vessel sealer (EBVS; LigaSure Atlas) is a modern device that allows the secure sealing of vessels with a diameter of up to 7 mm. The aim of the present study was to evaluate the suitability of the device for laparoscopic colonic surgery. METHODS: The immediate outcome of 114 consecutive patients who underwent a sigmoid or rectal resection was prospectively analyzed. The intention was to perform all operations with the EBVS for dissection and ligation of the mesenterial vessels. Details on patient characteristics, peroperative and postoperative complications, and postoperative recovery were recorded prospectively and analyzed. RESULTS: One hundred and fourteen patients were scheduled for elective left-sided colonic or rectal resection. Massive intra-abdominal adhesions in 1 patient required a conversion of the laparoscopic procedure to an open one; In total, 113 laparoscopic operations were thus performed. The mean operative time was 87.7 +/- 2.8 minutes, and the mean time for patients to tolerate solid food was 3.4 +/- 0.1 days and the time to discharge from hospital was 4.6 +/- 0.2 days. There were nine (8.0%) general complications, and additionally, 10.6% of patients suffered from surgical complications. CONCLUSIONS: The electrothermal bipolar vessel sealer is suitable and safe for laparoscopic sigmoid and rectal resections. The use of the device probably reduces the operative time.

Prognostic significance of matrix metalloproteinases-1, -2, -7 and -13 and tissue inhibitors of metalloproteinases-1, -2, -3 and -4 in colorectal cancer.

Strong expression of many matrix metalloproteinases (MMPs) has been related to poor survival of colorectal cancer (CRC) patients. The expression of tissue inhibitors of metalloproteinases (TIMPs) has been associated with both a beneficial and a poor outcome and there is thus a need to further clarify the significance of MMPs and TIMPs in CRC. The prognostic significance of 4 MMPs and TIMPs in CRC was evaluated. Formalin-fixed, paraffin-embedded tissue arrayed samples of 351 patients with primary colon or rectal cancer of Dukes' stages A-D were selected for immunohistochemical staining of MMP-1, -2, -7 and -13, and TIMP-1, -2, -3 and -4. High expression of MMP-2 in the malignant epithelium as well as in the surrounding stroma was associated with reduced survival of colon cancer patients. Strong epithelial and stromal cytoplasmic staining of TIMP-3 was associated with a longer survival in rectal cancer patients, and here the interobserver variation for evaluating the degree of staining was lower than for epithelial staining. Strong stromal cytoplasmic staining of TIMP-4 predicted longer survival of rectal cancer patients. Multivariate analysis showed that stromal cytoplasmic TIMP-3 staining was the only marker of independent prognostic value. MMP-2 might be a useful prognostic marker in colon cancer, and TIMP-3 and TIMP-4 in rectal cancer, but the findings associated with stromal staining should be interpreted with some caution. Different biologic behavior or different genetic development may explain the differences between colon and rectal cancers regarding the expression of MMP-2, TIMP-3 and TIMP-4.