Transverse myocutaneous gracilis flap reconstruction is feasible after pelvic exenteration: 12-year surgical and oncological results.

INTRODUCTION: Pelvic exenteration (PE) is the only curative treatment for certain locally advanced intrapelvic malignancies. PE has high morbidity, and optimal reconstruction of the pelvic floor remains undetermined. MATERIALS AND METHODS: A retrospective chart review was performed at a tertiary university center to assess the surgical and oncological outcomes of 39 PE procedures over a 12-year period. The majority of patients (n = 25) underwent transverse musculocutaneous gracilis (TMG) flap reconstruction for pelvic floor reconstruction. RESULTS: The 1- and 5-year overall survival (OS) was 72% (95%CI 58%-86%) and 48% (95%CI 31%-65%), respectively. In multivariate analysis, lymph node metastasis (HR 3.070, p = 0.024) and positive surgical margins (HR 3.928, p = 0.009) were risk factors for OS. In this population, 71.8% of the patients had at least one complication. The complication rate was 65.4% and 84.6% for patients with versus without flap reconstruction, respectively (p = 0.191). The length of stay was longer for patients with a major complication 16,0 ±â€¯5,9 days vs. 29,4 ±â€¯14,8 days, p = 0,001, but complications did not affect OS. CONCLUSION: For selected patients, PE is a curative option for locally advanced, residual, or recurrent intrapelvic tumors. Pelvic floor and vulvovaginal defects can reliably be reconstructed using TMG flaps. TMG flaps are favored in our institution over abdominal-based flaps because the donor site morbidity is reasonable and TMG does not interfere with enterostomy.

High YKL-40 is associated with poor survival in patients with renal cell carcinoma: a novel independent prognostic marker.

OBJECTIVE: YKL-40 is an inflammation-associated glycoprotein supposed to have a role in cell survival and angiogenesis. Renal cell carcinoma (RCC) is characterized by varying prognosis and risk of relapse after a disease-free period of years. Prognostic markers are critically needed. This study investigated whether YKL-40 could be a useful biomarker in RCC patients. MATERIALS AND METHODS: Blood samples from 82 patients with RCC were collected at the time of diagnosis and 3, 5 and 9 months and 2 and 3 years after nephrectomy. YKL-40 levels were determined by enzyme-linked immunosorbent assay. Survival of patients and relapse of RCC were followed up to 15 years. RESULTS: Circulating YKL-40 levels were increased in patients with metastatic RCC at the time of diagnosis (median 115.7 ng/ml, interquartile range 61.0-221.6 ng/ml). Among patients primarily diagnosed with non-metastatic RCC, baseline YKL-40 levels were significantly higher in patients who experienced a relapse during follow-up (103.7, 59.3-242.0 ng/ml) than in patients without relapse (50.6, 33.8-97.1 ng/ml). High baseline YKL-40 was highly associated with poor prognosis in RCC: in age-adjusted univariate analysis, YKL-40 over 120 ng/ml (highest tertile) predicted over five-fold mortality in 5 years, and in multivariate analysis high YKL-40 remained a statistically significant independent risk factor for 5 and 15 year survival. CONCLUSIONS: Increased circulating YKL-40 levels were significantly associated with poor survival in patients with RCC. The results suggest YKL-40 as a useful novel biomarker in evaluating prognosis and relapse risk in RCC, being especially beneficial in patients primarily diagnosed with non-metastatic RCC.

Resistin and interleukin 6 as predictive factors for recurrence and long-term prognosis in renal cell cancer.

OBJECTIVES: The aim of the present study was to investigate prognostic factors for long-term outcome of renal cell cancer (RCC) in a cohort of patients treated before new antiangiogenic therapy modalities were introduced. Our specific aim was to explore resistin and interleukin 6 (IL-6) levels to find out cytokines potential to predict recurrence and survival in patients with RCC. MATERIALS AND METHODS: Our prospective study population consisted of 91 patients who underwent radical nephrectomy or partial resection for RCC at Tampere University Hospital between 1994 and 2001. At the time of surgery, 25 patients were diagnosed to have an advanced tumor and 66 patients a local tumor; 34 patients in the latter group developed a recurrence during the follow-up period of 15 years. Serum samples were collected preoperatively and at 3, 9, and 15 months and at 2, 3, 4, and 5 years postoperatively. IL-6 and resistin levels in serum were measured by immunoassay. RESULTS: Preoperative values of IL-6 (P = 0.006) and resistin (P<0.001) were higher in patients with advanced RCC when compared to patients with local tumors. Patients with local RCC who developed a recurrence during the follow-up period had higher preoperative IL-6 values (P = 0.003) than patients without a recurrence. Based on trajectory analysis of IL-6 and resistin levels, the patients were divided into 3 trajectory groups. According to multivariate analysis, the patients in the trajectory class of the increasing resistin values during the follow-up period had a statistically significantly higher risk for RCC progression (hazard ratio [HR] = 3.73, 95% CI: 1.52-9.13) and for poor survival (HR = 4.93, 95% CI: 1.79-13.6) than the patients in the lowest trajectory class. Furthermore, the patients in the trajectory class of the highest IL-6 values showed a significantly elevated risk for RCC progression (HR = 7.03, 95% CI: 3.00-16.5) and for RCC-related poor survival (HR = 6.09, 95% CI: 2.53-14.7), when compared to the patients in the trajectory class of the lowest IL-6 values. CONCLUSION: In patients with RCC, the elevated preoperative resistin levels associated strongly with an advanced disease. Based on Cox regression models and trajectory analysis, resistin values were associated with disease progression and a poor survival.

Long-term outcome of patients with frequently recurrent non-muscle-invasive bladder carcinoma treated with one perioperative plus four weekly instillations of mitomycin C followed by monthly bacillus Calmette-Guérin (BCG) or alternating BCG and interferon-α2b instillations: prospective randomised FinnBladder-4 study.

BACKGROUND: Recurrent TaT1 non-muscle-invasive bladder cancer (NMIBC) patients should be treated with immediate instillation of chemotherapy after transurethral resection of bladder tumour followed by instillation therapy. OBJECTIVE: To present long-term results of a study exploring the effect of initial mitomycin C (MMC) instillations followed by two types of immunotherapy for patients with frequently recurring NMIBC. DESIGN, SETTING, AND PARTICIPANTS: Between 1992 and 1996, 236 patients with frequently recurring TaT1 grade 1-2 NMIBC were enrolled in the prospective randomised multicentre FinnBladder-4 study. INTERVENTION: One perioperative plus four weekly instillations of MMC followed by monthly bacillus Calmette-Guérin (BCG) or alternating BCG and interferon (IFN)-α2b instillations for up to 1 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary end points were time to first recurrence and time to progression. Secondary end points were disease-specific mortality and overall survival. The principal statistical methods were the proportional subdistribution hazards model and Cox proportional hazards model plus cumulative incidence and Kaplan-Meier analyses. RESULTS AND LIMITATIONS: The median follow-up was 10.3 yr (maximum: 19.8 yr) in the MMC-BCG group and 8.6 yr (maximum: 19.8 yr) in the MMC-BCG/IFN group. The probability of recurrence was significantly lower in the MMC-BCG group than in the MMC-BCG/IFN group (43% vs 78% at 10 yr and 45% vs 80% at 15 yr, respectively; hazard ratio: 2.86; 95% confidence interval, 1.98-4.13; p<0.001). There were no significant differences in the probability of progression, disease-free mortality, or overall survival. CONCLUSIONS: Perioperative plus four weekly MMC instillations followed by monthly BCG, instead of alternating BCG and IFN-α2b instillations, significantly reduce long-term recurrence. PATIENT SUMMARY: We demonstrated in non-muscle-invasive bladder cancer patients with exceptionally frequent recurrences that the risk of long-term recurrence was reduced from 78-80% to 43-45% if one perioperative plus four weekly mitomycin C instillations were followed by monthly bacillus Calmette-Guérin (BCG) instillations for 1 yr instead of alternating instillations of BCG and interferon-α2b. TRIAL REGISTRATION: The registration was not considered necessary at this stage of the follow-up because the study was initiated as early as in 1992 and the last randomisation took place in 1996, before the current requirements concerning study registrations were implemented.

Reconstruction of the pelvic floor and the vagina after total pelvic exenteration using the transverse musculocutaneous gracilis flap.

BACKGROUND: Total pelvic exenteration (TPE) is a rare operation in which the pelvic contents are removed entirely. Several options for pelvic floor and vaginal reconstruction have been described including transverse rectus abdominis musculocutaneous (TRAM) or deep inferior epigastric perforator (DIEP) flaps. The transverse musculocutaneous gracilis (TMG) flap has been introduced for breast reconstruction as a free flap. We adopted the pedicled TMG flap for reconstructions after TPE. To the best of our knowledge, this is the first report of this method in the literature. METHODS: Between November 2011 and February 2014, 12 patients underwent TPE and reconstruction with unilateral (six patients) or bilateral (six patients) pedicled TMG flaps. Five patients underwent vaginal reconstruction with bilateral TMG flaps. We describe the operative procedure and the outcome of the operation in these patients. RESULTS: The total mean operative times for TPE with or without vaginal reconstruction were 467 ± 12 and 386 ± 59 min, respectively. The TMG flaps had enough vascular tissue and mobility for reconstructing the TPE defects. There was distal edge necrosis in one out of 18 flaps, while the rest survived completely. During the follow-up, complete wound healing with no signs of weakening of the pelvic floor was observed in all cases. CONCLUSIONS: Soft-tissue reconstructions are needed to reduce complications associated with TPE, to secure the pelvic floor and to reconstruct the vagina in select patients. The TMG flap is a logical flap choice that does not lead to functional deficits, complicate the abdominal ostomies or weaken the abdominal wall. It reduces the length of operation compared to that of abdominal flaps. LEVEL OF EVIDENCE: IV, therapeutic.

Genetic variation in platelet integrin alphabeta (GPIIb/IIIa) and the metastatic potential of renal cell carcinoma.

OBJECTIVE: To explore whether genetic polymorphisms in platelet receptors known to be associated with platelet activity have any association with haematogenous metastases in renal cell carcinoma (RCC), as platelets and their fibrinogen receptors may be central to haematogenous cancer spread, in addition to various adhesive proteins on both platelets and tumour cells on themselves. PATIENTS AND METHODS: The glycoprotein alpha(IIb)beta3 (GPIIb/IIIa) is the main fibrinogen receptor on platelets, with GPIb-IX-V and GPIa/IIa being the von Willebrand Factor and collagen receptors, respectively. In a cross-sectional survey of 128 men treated for RCC (55 with disseminated disease and 73 with a local disease), they were genotyped using DNA extracted from freshly drawn blood, and central clinical data were recorded. RESULTS: The frequency of possessing the GPIIIaPl(A2) allele among patients with metastatic RCC was 43.6%, and with local disease was 24.7% (P = 0.024). The frequencies of the different alleles of the GIB-IX-V, C3550T and GPIa/IIa C807T polymorphisms did not differ between the groups. In a stepwise logistic regression (metastatic vs local RCC) the Pl(A2) allele remained a significant risk factor, with an odds ratio of 2.7 (95% confidence interval, 1.1-6.5; P = 0.02). CONCLUSION: The prothrombotic Pl(A2) allele of platelet fibrinogen receptor GPIIb/IIIa increased the risk of metastases in RCC in men.

Renal cell carcinoma MIB-1, Bax and Bcl-2 expression and prognosis.

PURPOSE: Proliferation and programmed cell death (apoptosis) are key factors in oncogenesis and tumor progression. In carcinogenesis important regulators of apoptosis are members of the Bcl-2 family. In this family the Bcl-2 gene has an inhibitory effect on apoptosis, while Bax promotes cell death. In renal cell carcinoma (RCC) the associations between Bcl-2 proteins and RCC prognosis have been controversial. We evaluated Bax and Bcl-2 levels in RCC, and their associations with prognosis, proliferation and traditional prognostic factors. MATERIALS AND METHODS: Our prospective study population comprised 138 consecutive patients who underwent radical nephrectomy for RCC. Immunostaining and semiquantitative indices for Ki-67 (MIB-1), Bax and Bcl-2 were estimated. Their associations with prognosis were explored. RESULTS: On univariate analysis according to survival statistically significant differences were achieved by Bax (positive vs negative HR 3.04, 95% CI 1.27 to 7.23), Bcl-2 (positive vs negative HR 0.43, 95% CI 0.23 to 0.81), MIB-1 (continuous HR 1.03, 95% CI 1.001 to 1.064), Fuhrman nuclear class (4 vs 1 plus 2 HR 8.15, 95% CI 3.13 to 21.20) and stage (4 vs 1 HR 60.04, 95% CI 13.99 to 257.68). Only stage (HR 47.96, 95% CI 10.85 to 212.03) and Fuhrman classification (HR 4.32, 95% CI 1.60 to 11.65) attained statistical significance on Cox regression multivariate analysis. CONCLUSIONS: In our prospective study Bax and Bcl-2 showed a statistically significant association with prognosis in RCC but did not achieve the status of independent prognostic factors. Further studies are needed to clarify the role of the apoptotic process in tumor progression and prognosis.

Status of pretreatment evaluation, treatment and follow-up regimens for renal cell carcinoma in the Nordic countries.

OBJECTIVE: One prerequisite for performing multicentre studies is that the clinical handling of the patients must be uniform. We therefore evaluated possible differences in pretreatment evaluation, surgical treatment and follow-up regimes between the Nordic countries and between the different departments that performed nephrectomy due to renal cell carcinoma. MATERIAL AND METHODS: A questionnaire comprising 21 different questions was sent to all hospitals in the five Nordic countries performing nephrectomy. The questionnaires were returned by 195/226 (86%) departments. RESULTS: In total, 24% of the departments performed fewer than five tumour nephrectomies per year. The main differences were as follows. I.v. pyelography was never used in Finland in clinics with urologists while preoperative CT scans were performed by most departments and in most countries. Cytology/biopsy examinations were never used in urological clinics in Finland and Iceland in contrast to 31% of urological clinics in Denmark. In Finland, 69% of the departments performed nephrectomy in patients with multiple distant metastases, compared to only 15% in the other Nordic countries. Follow-up after nephrectomy was done in 38% of Danish departments and in 96% of departments in the other Nordic countries. CONCLUSION: There were evident differences between the urological/surgical departments in the five Nordic countries, especially concerning radiological evaluation, treatment of patients with metastases and postoperative follow-up.

Differences between local and review urinary cytology in diagnosis of bladder cancer. An interobserver multicenter analysis.

OBJECTIVES: The objective of the study is to evaluate the agreement of local and review urinary cytology in patients with newly diagnosed bladder cancer and in those being followed for their disease. In addition, the effect of the type of institution on agreement was determined. METHODS: A total of 652 consecutive patients with bladder cancer from 19 institutions were evaluated; 575 (88.2%) of the patients had cytopathological sample available for central review and were eligible for analysis. One hundred and twenty nine (22.4%) of the patients had newly diagnosed bladder cancer, whereas the remaining 446 (77.6%) patients were under follow-up. A voided urine sample was obtained prior to transurethral resection of the bladder (TURB) or routine follow-up cystoscopy and split for culture and cytology. The cytopathological samples were first analysed by a local pathologist, and then re-analysed by a central reviewer. The agreement of cytological readings was determined by Kappa coefficient. RESULTS: The sensitivities of local and review cytology in detection of primary bladder cancer were 38.8 and 31.0%, respectively. Recurrence was observed in 119 of the 446 (26.7%) patients under follow-up, of which both local and review cytology detected 21 (17.6%) cases. Specificities of local and review cytology were 97.6 and 96.6%, respectively. Overall agreement of urine cytology was good in patients with primary bladder cancer and moderate in those being followed for their disease as Kappa coefficients were 0.70 and 0.60, respectively. However, some disagreement was found when results were analysed according to type of institution, to type of primary tumour, and to result of follow-up cystoscopy. In patients with primary bladder cancer the Kappa coefficient was 0.86 (very good) in university hospitals and 0.36 (fair) in city hospitals. Accordingly, in patients under follow-up the Kappa coefficient was 0.65 (good) in university hospitals and 0.39 (fair) in district hospitals. Although the stage of primary tumour had no effect on agreement, agreement was moderate (Kappa coefficient 0.45) in those with low grade tumour and good (Kappa coefficient 0.67) in those with high grade tumour. In addition, Kappa coefficients were 0.65 (good) and 0.40 (fair) in those with and without recurrence at follow-up cystoscopy. CONCLUSIONS: Although overall agreement of routine cytology was from moderate to good in both diagnosis and monitoring of bladder cancer, there is some variation in agreement according to the type of institution. Accordingly, grade of primary tumour and the result of follow-up cystoscopy had effect on agreement reflecting subjectiveness and weak reproducibility of this test. This not only emphasises the need for continuing education and quality control for urine cytologic analysis, but also inspires the development of more objective tests.