Ki-67 Expression is a Prognostic Marker of Prostate Cancer Recurrence after Radical Prostatectomy

Purpose

We assessed the cellular proliferation of clinically localized prostate cancer by immunohistochemistry using the monoclonal antibody MIB to Ki-67 antigen in an attempt to identify associations between proliferative indexes and disease progression following radical prostatectomy.

Materials and Methods

Ki-67 proliferative antigen was evaluated using MIB 1 monoclonal antibody in archival paraffin embedded radical prostatectomy specimens from 180 patients followed for 1 to 9 years (mean 4.4). The percentage of tumor nuclei expressing Ki-67 antigen was measured and assigned an MIB 1 score (none or rare-negative, 1+-low score and 2 to 4+-high score) and analyzed for prostate specific antigen, stage, age, race, grade and serological recurrence postoperatively.

Results

There was a significant association between MIB 1 score and nuclear grade (p less than 0.001), Gleason score (p less than 0.001) and pathological stage (p = 0.01). Patients with a high MIB 1 score had earlier progression and a lower 5-year recurrence-free survival rate (44 percent) than those with negative MIB 1 scores (71 percent, p less than 0.001). In multivariate Cox regression analysis with backward elimination, pathological stage (p less than 0.01), pretreatment prostate specific antigen (p = 0.04) and MIB 1 score (p = 0.05) were statistically significant predictors of disease-free survival, and patients with a high MIB 1 score were 3.1 times as likely to have recurrence as those with a negative score. Controlling for stage, patients with organ confined disease and a high MIB 1 score had a lower 5-year disease-free survival rate (68 percent) than those with a low MIB 1 score (95 percent, p greater than 0.01).

Conclusions

Proliferative activity as measured by the Ki-67 proliferative antigen, MIB 1, appears to be a prognostic marker of recurrent prostate cancer after radical prostatectomy.     

Outcome Prediction of Pulmonary Metastasectomy Can Be Evaluated Using Metastatic Lesion in Osteosarcoma Patients

Background

We investigated whether molecular prognostic factors should be evaluated in specimens of the primary or the metastatic lesion and if the prognosis after initial pulmonary metastasectomy can be predicted based on evaluation of metastatic lesion specimens in osteosarcoma patients.

Methods

This retrospective study included 29 osteosarcoma patients with pulmonary metastases (19 males, 10 females; age 21 ± 10 years). Molecular prognostic factors were the levels of vascular endothelial growth factor type A (VEGF-A), VEGF type C (VEGF-C), and Ki67. Primary and pulmonary metastatic lesions could be compared in 18 patients regarding the values of marker expressions and the prognosis after initial pulmonary resection. Finally, the prognosis of all 29 cases was compared according to the molecular markers of the metastatic lesions.

Results

Evaluation of the metastatic lesions reflected the prognosis after pulmonary metastasectomy more than that of the primary lesions. In the metastatic lesions, positive expression of VEGF-A (n = 15), VEGF-C (n = 2), and Ki67 (n = 15) was associated with a significantly poorer prognosis (p = 0.0013, 0.0001, and 0.037, respectively). No patients with positive expression of both VEGF-A and Ki67 (n = 7) survived more than 5 years after the initial pulmonary resection. All patients who had negative reactions to both VEGF-A and Ki67 (n = 6) were alive at the end of the study.

Conclusions

Molecular prognostic factors should be investigated in specimens of the metastatic lesion. Combined evaluation of VEGF-A and Ki67 and of VEGF-C using pulmonary metastatic lesion specimens in osteosarcoma patients effectively reflects survival after pulmonary metastasectomy.     

Proliferative Index Determination in Prostatic Carcinoma Tissue: Is There Any Additional Prognostic Value Greater Than That of Gleason Score, Ploidy and Pathological Stage?

Purpose

The proliferative index was evaluated as an additional prognostic variable in 244 radical prostatectomy specimens from patients with prostate cancer. This study was done on the grounds that this variable has shown some promise as a prognostic tool in some other carcinomas, for example breast cancer.

Materials and Methods

The proliferative index was evaluated in 244 patients undergoing radical prostatectomy for clinically localized disease between January 1988 and August 1994. Proliferative index was determined using the Ki-67 antibody on fresh frozen tissue and MIB-1 on paraffin embedded tissues. Patients were divided into 2 groups based on a proliferative index of less than 1 (185) or 1 or greater (59). Of the patients 49 (20%) had biochemical failure (median 23 months to progressive prostate specific antigen elevation of 0.5 ng./ml. or more). Those whose treatment failed were also divided into 2 groups according to proliferative index: 32 of 185 (18%) with an index of less than 1 and 17 of 59 (27%) with an index of 1 or more. Gleason score and deoxyribonucleic acid ploidy status were also evaluated in all patients and compared in multivariate regression analysis. Operative specimens were categorized as organ confined, specimen confined or margin positive.

Results

The distribution according to margin status in the 2 groups (proliferative index less than 1 and 1 or more) was 40 versus 60% for organ confined, 67 versus 33% for specimen confined and 72 versus 28% for margin positive disease, respectively. The distribution of time to treatment failure in the 2 groups was not markedly different: 7.2 versus 9.4 months for margin positive, 10 versus 14.5 months for specimen confined and 8.5 versus 12 months for organ confined cancer, respectively.

Conclusions

Multivariate analysis demonstrated that, although deoxyribonucleic acid ploidy seemed to correlate with more advanced disease, only Gleason sum and pathological T stage reached statistical significance when evaluated against time to treatment failure. A high proliferative index added little above the more traditional prognostic indicators of Gleason score, pathological stage and ploidy. Therefore, we question the value of proliferative index as a prognostic indicator using the aforementioned methodology in prostate cancer.     

Predictors of survival in surgically treated patients of spinal metastasis

Background:

The spinal metastasis occurs in up to 40% of cancer patient. We compared the Tokuhashi and Tomita scoring systems, two commonly used scoring systems for prognosis in spinal metastases. We also assessed the different variables separately with respect to their value in predicting postsurgical life expectancy. Finally, we suggest criteria for selecting patients for surgery based on the postoperative survival pattern.

Materials and Methods:

We retrospectively analyzed 102 patients who had been operated for metastatic disease of the spine. Predictive scoring was done according to the scoring systems proposed by Tokuhashi and Tomita. Overall survival was assessed using Kaplan–Meier survival analysis. Using the log rank test and Cox regression model we assessed the value of the individual components of each scoring system for predicting survival in these patients.

Result:

The factors that were most significantly associated with survival were the general condition score (Karnofsky Performance Scale) (P=.000, log rank test), metastasis to internal organs (P=.0002 log rank test), and number of extraspinal bone metastases (P=.0058). Type of primary tumor was not found to be significantly associated with survival according to the revised Tokuhashi scoring system (P=.9131, log rank test). Stepwise logistic regression revealed that the Tomita score correlated more closely with survival than the Tokuhashi score.

Conclusion:

The patient''s performance status, extent of visceral metastasis, and extent of bone metastases are significant predictors of survival in patients with metastatic disease. Both revised Tokuhashi and Tomita scores were significantly correlated with survival. A revised Tokuhashi score of 7 or more and a Tomita score of 6 or less indicated >50% chance of surviving 6 months postoperatively. We recommend that the Tomita score be used for prognostication in patients who are contemplating surgery, as it is simpler to score and has a higher strength of correlation with survival than the Tokuhashi score.     

Inflammation-Based Prognostic System Predicts Postoperative Survival of Colorectal Cancer Patients with a Normal Preoperative Serum Level of Carcinoembryonic Antigen

Background

Although carcinoembryonic antigen (CEA) is a valuable indicator for estimating the progression of colorectal cancer (CRC), some patients with advanced CRC show no elevation of the CEA level. On the other hand, inflammation-based prognosis, assessed by the Glasgow Prognostic Score (GPS), has been established as one of the important prognostic factors of survival after surgery for several types of cancer. We estimated the postoperative survival of CRC patients with a normal preoperative serum level of CEA on the basis of the GPS.

Methods

Among 491 patients who had undergone elective CRC surgery, 271 with a normal preoperative serum CEA level (??5.0?ng/ml) were enrolled. Uni- and multivariate analyses were performed to evaluate the relationship to overall survival. Kaplan?CMeier analysis and log rank test were used to compare the survival curves between patients with GPS 0 (group A), and 1 or 2 (group B).

Results

Univariate analyses using clinical characteristics revealed that lymphatic invasion, lymph node metastasis, platelet count, the serum levels of CEA and C-reactive protein, tumor, node, metastasis staging system (stage 0, I, II/III, IV), and the GPS (0/1, 2) were associated with overall survival. Among these characteristics, multivariate analysis demonstrated that the GPS and platelet count were associated with overall survival. Kaplan?CMeier analysis and log rank test demonstrated a significant difference in overall survival between groups A and B (P?Conclusions Even if CRC patients have a normal preoperative serum level of CEA before surgery, the GPS is able to predict their postoperative survival.     

Fluorescence in Situ Hybridization Identifies More Aggressive Types of Primarily Noninvasive (Stage pTa) Bladder Cancer

Purpose

We evaluated the genetic changes in cytological specimens of bladder cancer by fluorescence in situ hybridization, and related them to stage and grade of the tumor, ploidy, p53 and Ki-67 expression, and clinical outcome to determine a simple method to identify tumors with a poorer prognosis.

Materials and Methods

Using fluorescence in situ hybridization the numerical aberrations of chromosomes 7, 9 and 17 in barbotages and imprints of 50 patients with transitional cell cancer of the bladder were determined. Of the patients 29 had a primary stage pTa tumor, while 21 with stage pT1 or greater disease formed the control group. Data were compared to ploidy status, and Ki-67 and p53 immunoreactivity.

Results

Repeated monosomy 9 and haploid or diploid status on static ploidy determination were found in patients with primary stage pTa tumors without recurrence. Immunoreactivity of p53 was negative in all of these patients, while there was a low percentage of positive staining for Ki-67. Patients with recurrent and progressive disease had a high incidence of trisomy 7 and 17, aneuploid status and high positivity for both immunological markers. For chromosomes 7 and 17, and ploidy status bivariate analysis showed a significant difference.

Conclusions

The evaluation of chromosomal aberrations in barbotage and imprint specimens clearly establishes a relationship between chromosomal defects and aggressiveness of the tumor. The majority of nonaggressive stage pTa transitional cell carcinomas can be distinguished from potentially lethal cases by fluorescence in situ hybridization at a diagnostic point when the grading is not yet prognostic.     

Effects of risk factors and Ki-67 on rates of recurrence on patients who have undergone liver transplant for hepatocellular carcinoma

Purpose

We investigated the prognostic factors affecting recurrence including Ki-67 among patients who underwent liver transplantation for hepatocellular carcinoma.

Materials and Methods

The 50 patients with a diagnosis of hepatocellular carcinoma and cirrhosis included those with expanded criteria for hepatocellular carcinoma excluding subjects with major vascular invasion and metastases but not taking into account tumor size and number of tumor nodules.

Results

Twenty-eight patients had hepatocellular carcinoma characteristics outside the Milan criteria. Nineteen patients had unifocal; 31, multifocal hepatocellular carcinomas. Mean tumor size was 3.2 cm; mean tumor number was 5.06 lesions. Over a mean follow-up of 45.3 ± 22.6 months, we diagnosed, respectively 2 recurrences. Overall 1-, 3-, and 5-year patient survival rates were 95.6%, 88.4%, and 84.8% and disease-free survival rates, 92%, 78.4%, and 71%, respectively. The independent prognostic factors by multivariate analyses were the number of tumors and Ki-67 with a cutoff value of 10%.

Conclusion

Ki-67 staining percentage represent a marker to select recipients and to follow posttransplant recurrence.     

Prognoses and treatment strategies for synchronous peritoneal dissemination of colorectal carcinoma

Purpose

We devised a simple dichotomous classification system and showed sufficient reproducibility to indicate treatment strategies for peritoneal metastasis of colorectal cancer.

Methods

We included 67 patients with peritoneal metastasis of colorectal cancer and classified them according to the largest lesion size, number of lesions and number of regional peritoneal metastases. The oncological data were recorded and compared.

Results

According to the univariate analyses, the prognoses were significantly better in patients with ≤3 disseminated lesions than in those with ≥4, and in patients with disseminated lesions in only one region than in those with ≥2 lesions. A multivariate analysis showed that primary tumor resection and the presence of peritoneal metastases in only one region were favorable factors for the patient survival. Patients with disseminated lesions in only one region (localized group) and those with nonlocalized lesions had three-year survival rates of 45.6 and 12.2 %, respectively. Finally, primary tumor resection improved the prognoses in both the localized and nonlocalized groups.

Conclusions

Colorectal cancer patients were categorized into localized and nonlocalized groups according to the number of regions with peritoneal metastasis, and significant prognostic associations were demonstrated. Subsequent analyses of the oncological data suggested that primary tumor resection contributes to an improved prognosis in all patients with synchronous peritoneal metastases.

     

Obesity paradox in prostate cancer: increased body mass index was associated with decreased risk of metastases after surgery in 13,667 patients

Introduction

Obesity might negatively affect prostate cancer (PCa) outcomes. However, evidence according to the associations between obesity and metastases-free survival after radical prostatectomy (RP) is still inconsistent.

Methods

We relied on PCa patients treated with RP at the Martini-Klinik Prostate Cancer Center between 2004 and 2015. First, multivariable Cox regression analyses examined the impact of obesity on metastases after RP. Last, in a propensity score matched cohort, Kaplan–Meier analyses assessed metastases-free survival according to body mass index (kg/m²) (BMI) strata (≥ 30 vs. < 25).

Results

Of 13,667 individuals, 1990 (14.6%) men were obese (BMI ≥ 30). Median follow-up was 36.4 month (IQR 13.3–60.8). Obese patients were less likely to exhibit metastases after RP (HR 0.7, 95% CI 0.5–0.97, p = 0.03). Similarly, after propensity score adjustment, obesity was associated with increased metastases-free survival (log rank p = 0.001).

Conclusion

We recorded the obesity paradox phenomenon in PCa patients. In particular, high BMI (≥ 30) was associated with decreased risk of metastases after RP, despite an increased risk being anticipated. Whether statin use might have affected the results was not assessed. Further research is needed to unravel the controversially debated association between obesity and PCa.

     

Clinical Evaluation of Cell Deoxyribonucleic Acid Content Measured by Flow Cytometry in Bladder Cancer

Purpose

We evaluated the clinical value of flow cytometry in bladder cancer.

Materials and Methods

Deoxyribonucleic acid (DNA) content was measured by flow cytometry in 275 untreated patients with bladder tumor followed for 1 to 8 years. Four pathological parameters (stage, grade, observed vascular invasion and associated carcinoma in situ) and 3 flow cytometric parameters (ploidy, number of aneuploid cell lines and DNA index) were defined.

Results

Univariate survival analysis showed that every parameter, when considered separately, was a significant prognostic factor (p less than 0.0001 in all cases). Multivariate analysis showed that stage (p less than 0.0001), DNA index (p less than 0.01) and associated carcinoma in situ (p less than 0.05) were independent, significant prognostic factors. However, ploidy and DNA index enhanced prognostic information above the traditional stage and grade only in patients with a stage pT1, grade 3 tumor (p less than 0.05). Retrospectively, different therapeutic decisions could have been made using DNA content only in 4 percent of cases.

Conclusions

In patients with bladder cancer DNA content is an independent predictor of survival but its clinical usefulness is limited.     

Combined resection of colorectal hepatic–pulmonary metastases shows improved outcome over chemotherapy alone

Background

The objective of this retrospective study was to assess the survival of patients after resection of hepatic and pulmonary colorectal metastases to identify predictors of long-term survival.

Methods

Patients receiving chemotherapy alone were compared to patients receiving surgery and chemotherapy in a matched-pair analysis with the following criteria: UICC stage, grading, and date of initial primary tumor occurrence.

Results

A total of 30 patients with liver and lung metastases of colorectal carcinoma underwent resection. In 20 cases, complete resection was achieved (median survival, 67 months). Incomplete resection and preoperatively elevated carcinoembryonic antigen (CEA) levels are independent risk factors for reduced survival. Patients developing pulmonary metastases prior to hepatic metastases had the worst prognosis. Surgical resection significantly increased survival compared to chemotherapy alone in matched-pair analysis (65 vs. 30 months, p?=?0.03).

Conclusions

Incomplete resection and elevated CEA levels are predictors of poor outcome. Matched-paired analysis confirmed that surgical resection in combination with chemotherapy appears to be superior to chemotherapy alone.     

Metastatic Melanoma to the Colon,Rectum, and Anus: A 50-Year Experience

Background

Melanoma metastatic to the large bowel (colon, rectum, and anus) is rarely diagnosed, with more than 95% of large bowel metastases identified post-mortem. The incidence, natural history, and survival rates of patients with large bowel melanoma metastases are poorly documented in the literature.

Objective

This study aimed to identify the incidence, clinical characteristics, and survival of patients with large bowel melanoma metastases.

Methods

A review was undertaken of all patients with melanoma treated over a 50-year period (1964–2014) at a tertiary referral center. Cases selected for study were those diagnosed with melanoma metastases in the colon, rectum, and anus. Primary colorectal and anal melanomas were excluded. Data were retrieved relating to patient demographics, clinical features, and survival.

Results

Of 38,279 patients with primary melanoma, 106 patients (0.3%, mean age 51.0 years [standard deviation 16.3], 64 males) developed large bowel metastases. The median interval between diagnosis of primary melanoma and large bowel metastasis was 62.8 months (range 1–476). The most common symptom was rectal bleeding (29.2%), and the large bowel was the sole site of metastasis in 47.2% of patients. Median survival from diagnosis of large bowel metastasis was 31.7 months (range 1–315), and overall survival at 1, 2, and 5 years was 68.1, 45.9, and 26.5%, respectively.

Conclusion

Our study provides insights into melanoma metastatic to the colon, rectum, and anus, which had an incidence of 0.3%. There are potentially long intervals between diagnosis of primary melanoma and large bowel metastasis. The most common symptom was rectal bleeding, although some patients were asymptomatic.

     

Prognostic role of Ki-67 score in localized prostate cancer: A systematic review and meta-analysis

Background

Ki-67 for quantifying tumor proliferation is widely used. In localized prostate cancer (PCa), despite a suggested predictive role of Ki-67 for outcomes after therapies, it has not been incorporated into clinical practice. Herein, we conduct a systematic review and meta-analysis of the literature reporting the association of Ki-67 and disease outcomes in PCa treated radically.

Depth of Submucosal Tumor Infiltration and its Relevance in Lymphatic Metastasis Formation for T1b Squamous Cell and Adenocarcinomas of the Esophagus

Background

Surgery for early esophageal carcinoma has been challenged by less invasive endoscopic approaches. Selecting patients in need for surgical intervention according to their risk of lymphatic spread is mandatory.

Objective

The aim of this study was to evaluate risk factors for lymphatic metastasis formation in T1b esophageal carcinomas.

Methods

Histopathological specimens following surgical resection for T1b esophageal carcinomas were reevaluated for overall submucosal layer thickness, depth of submucosal tumor infiltration, tumor length as well as lymphatic and vascular infiltration. Depth of tumor infiltration to overall submucosal thickness was divided in thirds (SM1, SM2, and SM3) and factors influencing lymphatic metastasis formation were assessed.

Results

A total of 67 patients with pT1b tumors were analyzed, including 36 adenocarcinomas (53.7 %) and 31 squamous cell carcinomas (46.3 %). Lymph node involvement was seen in 22.4 % (15/67) patients without significant differences between SM1 3/11 (27.3 %), SM2, 4/18 (22.2 %), and SM3 (8/38) (21.8 %) (p?=?0.909) carcinomas. On binomial log-regression models, only lymphangioinvasion and tumor length >2 cm was significantly associated with lymph node involvement.

Conclusion

As depth of submucosal tumor infiltration did not correlate with the formation of lymph node metastases and in regard of the risk of lymphatic spread in these cases, surgical resection is warranted in pT1b carcinomas.     

Chromosomal Anomalies in Stage D1 Prostate Adenocarcinoma Primary Tumors and Lymph Node Metastases Detected by Fluorescence in Situ Hybridization

Purpose

We determined if characteristic chromosomal anomalies exist within the primary tumors and lymph node metastases in patients with stage D1 prostate cancer, and compared the patterns of chromosomal alterations between primary tumors and nodal metastases.

Materials and Methods

Fluorescence in situ hybridization analysis using peri-centromeric probes for chromosomes 6, 7, 8, 17, X and Y was performed on 5 micro. sections from paraffin embedded tissue blocks obtained from 23 consecutive patients who underwent radical prostatectomy and bilateral pelvic lymphadenectomy in 1990 for stage D1 prostate cancer.

Results

The dominant focus of primary tumor was compared to matched nodal metastases in 12 cases. Five of 12 primary tumor foci (41.7%) had similar chromosomal gains and the same fluorescence in situ hybridization ploidy result as the corresponding nodal metastases. Chromosomes 7 and X (73.2% of cases) were most frequently gained in the primary tumors, and chromosomes X and Y (81.2% of cases) were most frequently gained in the metastases. No primary tumor or metastasis demonstrated chromosomal loss. Three of 19 primary tumors (15.7%) were diploid, while 16 of 19 (84.3%) were nondiploid. Chromosomal aneusomy was inversely correlated with increasing Gleason summary score.

Conclusions

These data indicate that the dominant primary tumor foci may not give rise to nodal metastases, gains of chromosomes 7, X and Y may be associated with metastatic behavior, and patients with stage D1 disease have a greater rate of aneuploidy than those with lower stage cancer.     

Landscape of chromosome number changes in prostate cancer progression

Purpose

Both genetic instability resulting in aneuploidy and increased proliferative activity are common features of tumor development and progression. Cytometric evaluation of tumor ploidy status was recently suggested as a prognostic marker. However, in prostate cancer (PCa), a chromosome-specific evaluation is lacking. With the present study, we sought to identify distinct chromosomal changes to complement cytometric results concerning the diagnosis and prognosis of PCa patients.

Methods

We assessed a cohort of 428 PCa specimens (186 localized PCa, 75 lymph node metastasized PCa, 125 lymph node metastases, 42 hormone-refractory distant metastases) for numerical alterations of all 24 chromosomes by using fluorescence in situ hybridization (FISH). Conducting immunohistochemistry with phosphorylated histone H3 (PHH3) and Ki-67, we quantified the proliferation rate. FISH results were fit in a linear model and tested for predictive power.

Results

As expected, we observed a significant increase in aneuploidy with advancing tumor stage. Similarly, an increased expression of the mitotic marker PHH3 was significantly associated with aneuploidy and higher pT-stage. We found aneusomy of chromosomes 4, 6, 20, and X to be indicative of lymph node metastasized PCa. However, with an AUC of 65 %, this set of chromosomal changes was poorly suited to distinguish non-metastasized and lymph node metastasized primary tumors.

Conclusion

Our results provide thorough insight into the so far incompletely elucidated chromosomal landscape of PCa. While overall ploidy status and PHH3 expression in primary tumors indicate advanced disease, a FISH-based test for distinct alterations does not seem to be beneficial for diagnostic or prognostic decisions.     

Surgery for Metachronous Solitary Liver Metastases of Renal Cell Carcinoma

Purpose

The postoperative outcome and survival of patients undergoing surgery for metachronous solitary liver metastases of renal cell carcinoma were evaluated.

Materials and Methods

Between 1983 and 1993, 17 patients with metachronous liver metastases of renal cell carcinoma underwent laparotomy for metastatic liver disease. All patients had undergone radical nephrectomy a mean of 3.6 years before the diagnosis of liver metastases.

Results

Surgical resection was feasible in 13 of 17 patients with right hemihepatectomy in 9 (3 multivisceral resections), wedge resection in 4 and ex situ (mobilization and eversion out of the abdomen) resection in 1. Stage RO resection (complete removal, negative surgical margins with no macroscopic disease left behind) was possible in 11 of 13 cases (85%). In patients with metastatic liver tissue resection the mortality rate was 31% (4 of 13) with additional significant morbidity in another 2. Mean survival of patients with nonresectable disease was 4 months, which increased to 16 months after resection.

Conclusions

Complete resection of metachronous liver metastases can be achieved in the majority of patients. However, significant morbidity and mortality as well as the limited prognosis even after RO resection strongly suggest careful patient selection.     

Reconstruction of the proximal femur with a modular resection prosthesis

Background

Various megaprostheses are currently available for reconstruction of the proximal femur after tumor resection. This study evaluates the survival and complications of a modular megaprosthesis for reconstruction of the proximal femur.

Materials and methods

We studied the medical files of 109 tumor patients (age range 16–86 years) who underwent proximal femoral reconstruction with the MRP^® megaprosthesis from 2002 to 2011. There were 70 patients with metastases, 34 patients with bone sarcomas, and five patients with hematological malignancies; 82 were primary and 27 were revision reconstructions. Mean follow-up was 2.5 years; 31 patients had a minimum five-year follow-up. We evaluated the survival and function of the patients, and the survival and complications of the megaprostheses.

Results

Survival was significantly higher for the patients with bone sarcomas compared to those with metastases and hematological malignancies. Mean MSTS functional score was similar between patients with bone sarcomas and those with hematological malignancies and metastases, and between patients with primary and those with revision reconstructions. Overall survival of the MRP^® megaprostheses was 74 % at 5 and 9 years. Fourteen (13.6 %) major complications occurred at a mean period of 1.4 years (range 3 months to 4.5 years); these included infection (5.8 %), dislocation (3.9 %), local recurrence (2.9 %), and acetabular fracture (1 %).

Conclusion

MRP^® megaprostheses are a valuable reconstruction option after tumor resection of the proximal femur.

     

Expression of β-catenin in regenerating renal tubules of cisplatin-induced kidney failure in rats

Background

β-Catenin is a multi-functional protein involved in nephrogenesis and also plays important roles in renal injury. Here, the expression of β-catenin was investigated in the proximal renal tubular epithelial cells in cisplatin (CDDP)-induced acute kidney injury (AKI) and chronic kidney injury (CKI), because CDDP-induced renal lesions were characterized by proximal renal tubular epithelial degeneration/regeneration and subsequent interstitial fibrosis.

Methods

F344 rats were treated with CDDP. The expression of β-catenin and proliferative (Ki67) or fibrogenic [vimentin, α-smooth action (α-SMA)] markers was analyzed by immunolabeling.

Results

β-Catenin, vimentin and Ki67 were not seen in the proximal renal tubules of control rats. Interestingly, in CDDP-induced AKI, the regenerating proximal renal tubular epithelial cells reacting strongly with Ki67 expressed membranous or cytoplasmic β-catenin and also showed a positive reaction to vimentin but not to α-SMA. In CDDP-induced CKI, the epithelial cells of abnormally dilated or atrophied renal tubules did not react to β-catenin or Ki67, but showed positive reactions to vimentin and α-SMA. β-Catenin mRNAs were significantly increased in AKI and significantly decreased in CKI.

Conclusion

Newly expressed β-catenin in the proximal renal tubules after AKI may participate in functional regeneration. In CKI, epithelial cells of abnormal renal tubules did not express β-catenin but reacted to vimentin, and α-SMA might indicate the epithelial–mesenchymal transition (EMT) formation, because α-SMA is usually expressed in myofibroblasts forming via EMT. The presence or absence of β-catenin expression would become a marker for the EMT phenomenon in progressive renal fibrosis.