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Overexpression of p53 in transitional cell carcinoma of the renal pelvis and ureter. Relation to tumor proliferation and survival.

BACKGROUND: Clinical management of patients with tumors of the upper urinary tract is based mainly on histologic grade and stage of the tumors. In recent years, tumor proliferation has also proved to be an important factor in determining the prognosis of these and other transitional cell tumors. The aim of this study was to assess the role of p53 in regulating cell proliferation and tumor progression and to define its value in predicting the long term survival of patients with these tumors. Such information could be of use in selecting treatment in individual cases. METHODS: Eighty-three patients with urothelial tumors of the renal pelvis and ureter diagnosed and treated between 1975 and 1993 were included in this study. p53 immunostaining was performed on paraffin embedded tissue. Tumor location, histologic grade, histologic pattern, tumor proliferation by Ki-67, local (T classification), lymph node (N classification), vascular and perineural invasion, and clinical stage (TNM) were assessed in relation to p53 overexpression (Mann-Whitney U test and analysis of variance comparisons) and as prognostic factors for survival in both univariate analysis (log rank test) and multivariate analysis (Cox proportional hazards model). RESULTS: Overexpression of p53 was related to tumor proliferation as assessed by Ki-67 (P < 0.01), T classification (Ta vs. T1-4; P < 0.01), N classification (P < 0.054), and TNM staging (Stage 0 vs. I-IV; P < 0.01). There was also a statistically significant relation to vascular (P < 0.002) and perineural invasion (P < 0.04). Fifteen-year actuarial survival for the whole group was 75%. Patients having tumors with low p53 overexpression (< 30% of stained nuclei) had a better survival rate (88%) than those having tumors with high (> 30%) p53 overexpression (65%) (P < 0.02), and this effect reached statistical significance with high grade (P < 0.02) and infiltrating tumors (P < 0.04). Patients with low p53 and Ki-67 expression had a 15-year survival rate of 100%; in contrast, patients with overexpression of both markers had a 15-year survival rate of 61% (P < 0.003). In a multivariate analysis, only T classification (P < 0.001) and p53-Ki-67 expression (P < 0.026) were statistically significant. CONCLUSIONS: Overexpression of p53 is related to increased tumor proliferation and disease progression and is of value in determining the long term survival of patients with tumors of the renal pelvis and ureter. p53 immunostaining can be used to distinguish low risk patients in the theoretically unfavorable high grade, high stage group, and when used together with Ki-67 index, it is a predictive factor for survival.

Adult↗

Carcinomas of the renal pelvis associated with smoking and phenacetin abuse: p53 mutations and polymorphism of carcinogen-metabolising enzymes.

Phenacetin abuse and smoking are established risk factors for transitional cell carcinomas of the urinary tract. In the present study, we analysed exposure and the clinical course of patients who underwent nephrectomy for transitional cell carcinoma of the renal pelvis. PCR-SSCP of archival, paraffin-embedded histological sections followed by direct DNA sequencing revealed that 29 of 89 (33%) renal pelvic carcinomas contained a p53 mutation. Double mutations were found in 4 tumours and triple mutations in 1 tumour. The incidence of p53 mutations was significantly higher in tumours with grades 3 and 4 than in those with grades 1 and 2 and higher in invasive than in non-invasive tumours. Furthermore, patients with carcinomas carrying a p53 mutation showed poorer survival than those without mutation. The type of p53 mutation in renal pelvic carcinomas was similar to that reported for bladder cancer, G:C-->A:T transition mutations being most frequent (45%, 33% of these at CpG sites), followed by G:C-->T:A and G:C-->C:G transversions. The incidence and type of p53 mutation did not differ significantly in patients with a history of phenacetin abuse, smoking or neither of these habits. This was also true for G:C-->T:A transversions (17.5% of mutations), which are considered typical of smoking-induced carcinomas at other sites, e.g., lung, oral cavity and oesophagus. Our results indicate that the frequency and pattern of p53 mutations are similar in transitional cell carcinomas of the bladder and the renal pelvis and do not reflect exposure to phenacetin and/or smoking. The frequency of genetic polymorphism in genes coding for carcinogen-metabolising enzymes (CYP1A1, NAT1, GSTT1 and GSTM1) was also independent of exposure. Although the sample size of our study does not allow definite conclusions, these data are compatible with chronic tissue damage as a causative factor in the evolution of urothelial carcinomas rather than pointing to a direct mutagenic effect of phenacetin and tobacco-specific carcinogens.

Aged↗

Morphometric analysis of the pelvis in mice treated neonatally with tamoxifen.

The pelves of male and female C57BL/Tw mice given five daily injection of 100 micrograms tamoxifen, 50 micrograms dihydrotestosterone (DHT), or 2 micrograms diethylstilbestrol (DES) from the day of birth were examined morphometrically and histomorphometrically. Total areas of the pelvis, ilium, ischium, and pubis were significantly smaller in neonatally tamoxifen-treated mice than in the controls. There was no significant difference in length of the ischium between tamoxifen-treated and control mice of both sexes. However, lengths of ilium and pubis, and widths of ilium, pubis, and ischium in tamoxifen-treated male and female mice were significantly smaller than in the respective controls. In contrast, neonatal treatment with DHT or DES did not affect the shape of the pelvis of either sex. In the neonatally tamoxifen-treated females, the number of osteoblasts and osteoclasts per 200 microns trabecular surface length and per 10,000 microns2 subperiosteal area of pubic bone section was smaller than in the controls. Inhibition of ossification persisted in the junction of the pubis and ischium of pelves treated with tamoxifen in vitro. These results suggest that neonatally administered tamoxifen mainly retards the growth of the ilium and pubis in mice by changing the activities of osteoclasts and osteoblasts, and that tamoxifen acts directly on the neonatal mouse pubis to inhibit its ossification.

Animals↗

The use of the saddle prosthesis for reconstruction of the hip joint after tumor resection of the pelvis.

Reconstruction of the hip joint by a saddle prosthesis after excision of a malignant pelvic tumor is a relatively new method, which thus far has been mainly used for revision of infected hip arthroplasties. One patient with a metastatic cystosarcoma phyllodes and one patient with a chondrosarcoma of the pelvis were treated by local resection and reconstruction with a saddle prosthesis. Although the patient with the metastatic cystosarcoma phyllodes died 9 months after surgery due to metastatic disease, both patients had early recovery, with no difference in leg length and obtained early painless complete weight bearing with satisfactory functional result. These two case reports clearly illustrate the usefulness of the saddle prostheses in limb saving surgery for malignant tumors of the pelvis.

Adult↗

Metastatic breast carcinoma to the abdomen and pelvis.

OBJECTIVE: The role of surgical resection of metastatic breast cancer to the abdomen and pelvis is controversial. The objective of this study is to describe the characteristics, surgical management, and outcome of women with a history of breast adenocarcinoma who developed abdominal or pelvic metastases during follow-up. METHODS: We retrospectively reviewed the medical records of 40 female patients with documented invasive breast cancer who were referred to the Gynecology Service between 1986 and 1995 and were found to have metachronous abdominal and/or pelvic metastases. RESULTS: The median patient age at exploration by the Gynecology Service was 53.5 years (range 27-79 years), and the median interval from breast cancer diagnosis to exploration was 80 months (range 9-264 months). The majority of patients, 32 (80%), had a preoperative diagnosis of a new pelvic mass or suspected abdominal carcinomatosis. With a median follow-up of 14.2 months following the diagnosis of abdominal or pelvic metastasis, the median survival for all patients was 24.1 months. Patients who had no gross residual disease in the abdomen or pelvis after surgery had a median survival of 41.6 months, which did not significantly differ from those with gross residual < or =2 cm (16.1 months) or >2 cm (18.4 months) (P = 0.624). CONCLUSION: Metachronous abdominal and pelvic metastases from breast cancer may appear many years following initial diagnosis and are often operated on by gynecologists because of their clinical presentation. Surgical resection may be indicated in some symptomatic patients; however, the survival advantage of surgical cytoreduction remains to be determined.

Abdominal Neoplasms↗

Ewing's sarcoma of the pelvis.

Two hundred and thirty-nine patients with Ewing's sarcoma were treated at our institution between 1972 and 1987: 42 of these had lesions in the pelvis, 29 were in the wing of the ilium or involved the sacroiliac joint (type I), 5 were periacetabular (type II), and 8 were in the anterior pelvic arch (type III). Radiotherapy alone was used for the primary lesion in 11 cases, adjuvant chemotherapy in 20 and a neoadjuvant protocol in 22. The overall disease-free survival at a mean follow up of 34 months was 19%. There was no difference in survival related to age or the site in the pelvis, none in disease-free survival with adjuvant and neoadjuvant chemotherapy, or in the incidence of local recurrence and metastases in these two groups. Similarly, there was no difference in disease-free survival between operative treatment, with or without radiotherapy, and radiotherapy alone. There was a slight trend towards better local control of the disease in the former group compared to the latter, although this difference was not statistically significant. Our conclusion is that treatment needs to be planned for each individual patient.

Adolescent↗

Gynaecological and sexual function related to anatomical changes in the female pelvis after restorative proctocolectomy.

Restorative proctocolectomy with an ileal pouch-anal anastomosis preserves anal sphincters, the normal route of defaecation and the normal body image and it has been suggested that the procedure might be associated with less gynaecological and sexual problems than conventional proctocolectomy. To shed further light on this subject 60 female patients were invited to participate in a study comprising a detailed interview, examination by a gynaecologist and investigation with hysterosalpingography and vaginography. Twenty-one women with a mean follow-up of 38 months after surgery agreed to participate. Their gynaecological state was considered normal although one woman complained of vaginal discharge. Five women experienced occasional dyspareunia and 2 patients had to take special precautions to avoid bowel leaks at intercourse. While the position of the vagina and uterus in the pelvis appeared normal, hysterosalpingography disclosed bilateral occlusion of the fallopian tubes in 2 and unilateral occlusion in another 9 patients with tubes adhering to the bottom of the lesser pelvis in 10 of the patients. Only one out of 14 patients succeeded in trying to conceive during the follow-up period. Among the remaining 39 women not specially studied 5 out of 14 had conceived after the operation.

Adult↗

Triple-stapled low colorectal anastomosis for the narrow pelvis.

Standard linear staplers for transverse occlusion of the rectum is sometimes too large to be applied in a narrow pelvis. A proximate TL 30 (Ethicon, Inc., Somerville, NJ) is easily introduced and applied twice for occlusion of the rectum, followed by anastomosis with a circular stapler. This triple-stapling technique is a safe and easy procedure for low colorectal anastomosis in a narrow pelvis.

Anastomosis, Surgical↗

Planoepithelial squamous cell carcinoma of the renal pelvis.

Two cases of planoepithelial squamous cell carcinoma of the renal pelvis are reported. Primary neoplasms of the renal pelvis are rare. Most are malignant and in the majority are of the transitional cell variety. Squamous cell carcinoma is an unusually rare occurrence.

Aged↗

Acute pyomyositis of the pelvis: the spectrum of clinical presentations and MR findings.

BACKGROUND: Acute pelvic pyomyositis is uncommon in non-tropical areas. OBJECTIVE: To summarize the clinical and MR findings in children with acute pelvic pyomyositis. MATERIALS AND METHODS: We retrospectively identified 20 children (mean age 9.4 years) who were evaluated by MR and diagnosed with acute pelvis pyomyositis during the time period between January 2002 and June 2005. We reviewed clinical, laboratory, and imaging findings. RESULTS: Fifteen of the 20 children had secondary pyomyositis associated with osteomyelitis (n=13), septic hip (n=4) or sacroiliitis (n=4); all were previously healthy except for one child with leukemia. Seven of the children with secondary pyomyositis underwent bone scintigraphy; three (43%) did not show pelvic abnormalities. Staphylococcus aureus was cultured in 13 of the 15 (87%) children. Five of the 20 children had primary pyomyositis. Three had underlying disease and two others were engaged in vigorous physical activity. Bone scintigraphies (n=2) were negative. Cultures were positive for S. aureus in three of the five (60%) children. CONCLUSION: Septic hip should be the first diagnostic consideration in children with fever and acute hip pain. Pyomyositis should be considered if arthrocentesis is negative or there is clinical suspicion of infection outside the hip joint. MR is the preferred imaging modality for evaluating foci of pyomyositis, muscle abscesses, and additional foci of infection within the pelvis.

Acute Disease↗

The AP diameter of the pelvis: a new criterion for continence in the exstrophy complex?

OBJECTIVE: Reconstructive surgery of bladder exstrophy remains a challenge. By using CT of the pelvis, we suggest a new pre- and post-operative investigative procedure to define the AP diameter (APD) as a predictive criterion for continence in this anomaly. PATIENTS AND METHODS: Three axial CT slices were selected in nine children with exstrophy who had undergone neonatal reconstructive surgery. The three levels selected were the first sacral plate, the mid acetabular plane and the superior pubic spine. We used combined slices to measure: APD = distance between the first sacral vertebra and the pubic symphysis. Pubic diastasis (PD). Three angles defined on the transverse plane of the first sacral vertebra--iliac wing angle, sacropubic angle and acetabular version. RESULTS: In exstrophy, the angles demonstrate opening of the iliac wings and the pubic ramus, and acetabular retroversion compared to controls. Comparisons between controls, continent and incontinent patients reveal that in continent patients, APD increases with growth and seems to be a predictive criterion for continence, independent of diastasis of the pubic symphysis. CONCLUSIONS: We believe that CT of the pelvis with measurements of the APD should be performed in all neonates with bladder exstrophy before reconstructive surgery and for better understanding of the malformation. The APD seems to be predictive and may be a major criterion for continence, independent of PD.

Bladder Exstrophy↗

Imaging features of low-grade central osteosarcoma of the long bones and pelvis.

PURPOSE: To determine the age and gender distribution and imaging features of low-grade central osteosarcoma (LGCOS) of the long bones and pelvis and to discuss our findings in the context of lesions for which LGCOS has been mistaken. MATERIALS AND METHODS: We reviewed 99 cases of LGCOS collected between 1919 and 2002 from our institution and pathology consultation files. Adequate imaging was available in 70 cases (36 radiographs only, 17 radiographs/CT, 12 radiographs/MRI, 2 radiographs/CT/MRI, 2 CT only, 1 MRI only, 5 bone scans). RESULTS: Patient average age was 30.1+/-14.2 years, with a slight female predominance. The femur and tibia were the most common long bones involved (29 and 20 each) with the majority of these tumors arising around the knee, followed by the fibula, radius, humerus and ulna (four, three, two and one case each). Flat bones were involved in six cases (three pelvis, one rib, two scapulae). Short tubular bones were involved in five cases (two metatarsal, two phalanges, one clavicle). The lesion extended to the end of the affected long bone in 22 of 59 cases. Lesions were large at presentation (mean 7.9+/-4.6 cm, range 2-24). Four radiographic patterns were identified: lytic with varying amounts of thick and coarse trabeculation ( n=22), predominantly lytic with few thin, incomplete trabecula ( n=21), densely sclerotic ( n=17) and mixed lytic and sclerotic ( n=10). Lesions were benign-appearing overall with focally aggressive features. CT or MRI demonstrated cortical breech or extension into the soft tissues in all cases. CONCLUSIONS: LGCOS has a variable appearance on radiographs. A frequent pattern is a slow-growing large intracompartmental fibro-osseous lesion with varying amounts of septal ossification associated with focal areas of aggression. A homogeneously sclerotic pattern was also noted. Imaging with CT or MRI was helpful in every instance in our series in identifying areas of soft tissue extension or cortical disruption suggestive of a low-grade malignancy.

Adult↗

Acute avulsion fractures of the pelvis in adolescent competitive athletes: prevalence, location and sports distribution of 203 cases collected.

OBJECTIVE: To describe the prevalence, location and sports distribution of pelvic avulsion fractures in adolescent competitive athletes. DESIGN AND PATIENTS: One thousand two hundred and thirty-eight radiographs of the pelvis taken for focal traumatic symptoms in athletes with an age range of 11-35 years over a period of 22 years were reviewed. RESULTS: One hundred and ninety-eight adolescent athletes were affected by 203 avulsion fractures of the pelvic apophyses (five cases presented multiple locations). The localisation was the ischial tuberosity (IT) in 109 cases, anterior inferior iliac spine (AIIS) in 45 cases, anterior superior iliac spine (ASIS) in 39 cases, superior corner of pubic symphysis (SCPS) in 7 cases and iliac crest (IC) in 3 cases. Soccer (74 cases) and gymnastics (55 cases) were the sports with the highest number of avulsion fractures documented. CONCLUSIONS: Apophyseal avulsion fractures of the pelvis in adolescent competitive athletes are most common in soccer and gymnastics. The lesions are usually the consequence of sudden and forceful muscle-tendon contractions during sport activities. Plain radiographs, are determinant for the diagnosis.

Adolescent↗

Variability of the spine and pelvis location with respect to the gravity line: a three-dimensional stereoradiographic study using a force platform.

Analyzing standing posture requires a precise measure of the orientation of the various body segments with respect to the gravitational vector. We studied the posture variability of 34 healthy upright standing subjects. Using a force platform combined with a powerful stereoradiographic technique, we acquired the spine and pelvis three-dimensional (3D) geometry and located it with respect to the gravity line. For our data set, the mean 3D distance between the geometrical center of each vertebral body and the gravity line was 28 mm with a standard deviation of 5.6 mm. The vertebrae location variability, defined as plus or minus twice the mean standard deviation, was +/-40 mm in the sagittal plane and +/-25 mm in the frontal plane. The line connecting the middle of the external acoustic meatus (center of both acoustic meati: CAM) to the middle of the bi-coxo-femoral axis (hip axis: HA) was almost vertical. Its mean distance to the gravity line was 30 mm. Our data show a left lateralization, with respect to the gravity line, of the "Head-Spine-Pelvis" segments. The mean distance was 7.6 mm (SD 1.6 mm). This might be due to uneven partitioning of the body mass on each side of the sagittal plane.

Adult↗

MR imaging and CT of the female pelvis: radiologic-pathologic correlation.

For imaging of the female pelvis, transvaginal ultrasound is the method of choice. Magnetic resonance imaging and CT provide important additional information in various disorders. Magnetic resonance imaging is superior to CT in diagnosing benign and malignant disorders of the uterus. The same holds for the characterization of adnexal masses, where MR imaging reliably differentiates dermoids, ovarian fibromas, and most endometriomas. Differentiation of other benign and malignant ovarian tumors by CT and MR imaging is based on identical morphological criteria; no superiority of MR imaging over CT has been established. Computed tomography is still the preferred imaging modality for staging ovarian cancer. A thorough knowledge of the pathomorphological changes associated with the different disorders of the female pelvis not only helps to choose the proper imaging modality and examination protocol, but also improves image interpretation.

Female↗

Bone tumors in the pelvis presenting growth during pregnancy.

Among 56 cases of a giant cell tumor of bone (GCT) and 52 cases of chondrosarcoma (CSA) in our series, four patients were discovered to have a tumor in the pelvic bone that grew in size during pregnancy. These four rare cases are described here. They include three cases of a GCT in the sacrum and one case of a CSA in the innominate bone. The dextran-coated charcoal assay and immunohistochemical techniques demonstrated the independence of these tumors from hormonal regulation despite the growth stimulated during pregnancy. It was concluded that the delay in detection of these tumors in the pelvis was just related to the opportunity afforded for unexpected growth during pregnancy. Surgical management was difficult due to the delay in tumor detection. The initial complaints such as pain, discomfort, or numbness around the pelvis were misinterpreted as symptoms of pregnancy. It should be kept in mind that during pregnancy, any pain or numbness in the pelvic region could be the direct result of a tumor in the pelvic bone.

Adult↗

Effects of trochanteric soft tissues and bone density on fracture of the female pelvis in experimental side impacts.

Pelvic fractures continue to be a source of morbidity and mortality for occupants in motor vehicle side impacts, especially among women. Previous studies have produced fracture tolerances for the female pelvis, yet the roles of soft tissues and bone quality remain unclear. Presently, we studied the influence of trochanteric soft tissue thickness (T) and total hip bone mineral density (BMD) on pelvic fracture of 10 female human pelves subject to lateral impact centered over the greater trochanter. Multiple impacts of increasing severity were performed and impact force, energy, impulse, compression, and viscous criteria were quantified. BMD and T were found to be additive predictors of the fracture force. For a given BMD, the force to fracture was significantly higher than that found previously using isolated pelvic bones. Impulse was found to positively correlate with T; however, maximum compression, viscous criterion, and energy to fracture were independent of BMD and T. The force tolerance at 25% probability of fracture found presently (3.16 kN) is substantially below previously reported values. The results suggest that the trochanteric soft tissue thickness and total hip BMD have a significant bearing on fracture outcome for the female pelvis in automotive side impact.

Accidents, Traffic↗

Clitoral metastasis from transitional cell carcinoma of the renal pelvis: CT and MRI findings.

Metastatic tumors of the clitoris are extremely rare. We report a case of clitoral metastasis in a 75-year-old woman who was treated for transitional cell carcinoma of renal pelvis 2 years ago. The computed tomography and magnetic resonance imaging findings are presented with a short review of the literature. To the best of our knowledge, clitoral metastasis originating from transitional cell carcinoma of the renal pelvis has not been reported in the English language literature.

Aged↗