The cell cycle inhibitors p21WAF1 and p27KIP1 are associated with survival in patients treated by salvage prostatectomy after radiation therapy.

We evaluated p27KIP1 and p21WAF1 expression in 52 patients treated by salvage radical prostatectomy and bilateral pelvic lymphadenectomy for biopsy-proven locally persistent or recurrent prostate cancer after external beam radiation therapy. We defined low and high expression based on the median value observed in our sample. Five-year distant metastasis-free survival and cancer-specific survival were 71 and 82%, respectively, for patients with low expression of p21 (< or =5%), compared with 94 and 100%, respectively, for those with high expression of p21 (>5%; P = 0.02 and 0.01, respectively). Five-year distant metastasis-free survival and cancer-specific survival were 71 and 82%, respectively, for patients with low expression of p27 (<50%), compared with 88 and 96%, respectively, for those with high expression of p27 (> or =50%; P = 0.06 and 0.01, respectively). These findings indicate that p21 and p27 expression levels are significant predictors of survival for patients selected for salvage prostatectomy for recurrent prostate cancer.

Cell proliferation in prostate cancer patients with lymph node metastasis: a marker for progression.

The biological aggressiveness of lymph node-positive prostate cancer is closely linked to cancer volume in nodal metastases. We evaluated MIB-1 (Ki-67) labeling index and bcl-2 expression in primary cancer and matched nodal metastases from 138 node-positive patients treated with radical prostatectomy and bilateral pelvic lymphadenectomy between 1987 and 1992 at the Mayo Clinic. One hundred twenty-eight patients (93%) received androgen deprivation therapy within 90 days after radical prostatectomy. Mean patient age was 66 years (range, 51-78). The median follow-up was 6.7 years (range, 0.03-11). MIB-1 (Ki-67) labeling index was determined by digital image analysis, and nodal cancer volume was determined by the grid method. Systemic progression, defined as the presence of distant metastasis documented by biopsy or radiographic examination, was used as an outcome end point in the Cox proportional hazard models. MIB-1 labeling index in nodal metastases was predictive of systemic progression-free survival (P = 0.001). The 8-year systemic progression-free survival was 100% for those with MIB-1 labeling index <3.5% compared with 78% for those with MIB-1 labeling index > or =7.8%. MIB-1 labeling index correlated with Gleason score, DNA ploidy, and nodal cancer volume (P<0.001, 0.04, and <0.001, respectively). After controlling for nodal cancer volume, MIB-1 labeling index remained significant in predicting systemic progression-free survival (P = 0.047). bcl-2 expression in the primary cancer and lymph node metastasis was associated with systemic progression-free survival in univariate analysis (P = 0.027 and 0.048, respectively) but was not significant after adjusting for nodal cancer volume (P = 0.52 and 0.17, respectively). Our data indicate that assessment of cell proliferation in nodal metastasis is predictive of clinical outcome in prostate cancer patients with regional lymph node metastasis.

Grading and staging of bladder carcinoma in transurethral resection specimens. Correlation with 105 matched cystectomy specimens.

We compared the grading and staging of transurethral resection of the bladder (TURB) and cystectomy specimens for 105 patients who underwent radical cystectomy for urothelial carcinoma between 1980 and 1984. Of 105 patients, 96% underwent cystectomy within 100 days of TURB (median interval, 10 days). Grading was performed according to the 1998 World Health Organization/International Society of Urologic Pathology grading system and staging according to the 1997 TNM classification. Histologic grade was low-grade, 13; high-grade, 92 in TURB specimens; low-grade, 17; high-grade, 88 in cystectomy specimens. Pathologic stage was Ta, 15; T1, 55; and T2, 35 in TURB specimens; Ta, 5; T1, 19; T2, 19; T3, 46; and T4, 16 in cystectomy specimens. Histologic grade at TURB was associated with pathologic stage at cystectomy (P < .001). When all advanced-stage (muscle-invasive) carcinomas (pT2 or more) were considered together, 55 patients were understaged by TURB, 4 had higher stage in TURB than in cystectomy, and 46 were the same stage as by cystectomy. Forty-three of 55 patients with stage T1 carcinoma at TURB had advanced-stage carcinoma at cystectomy, including 34 who had extravesicular extension (pT3 or more). We found pathologic understanding by TURB occurs in a significant number of patients with bladder cancer; the newly proposed grading system predicted final pathologic stage.

Multidisciplinary approach to traumatic intracranial aneurysms secondary to shotgun and handgun wounds.

BACKGROUND: Traumatic intracranial aneurysms (TICAs) may develop following gunshot injuries to the head. Management of these lesions often combines various aspects of microneurosurgical and endovascular techniques to safely repair or obliterate vessel defects. METHODS: We reviewed our experience over the last 18 years and identified five cases of intracranial aneurysms following gunshot and handgun wounds that were treated surgically and/or endovascularly. RESULTS: All patients had successful obliteration of their lesions using a variety of therapeutic modalities aimed at preserving neurologic function while at the same time eliminating the aneurysm from the circulation. CONCLUSION: Both microneurosurgery and endovascular surgery have important roles to play in the management of TICAs. In some cases, both methods can be combined to eliminate lesions and maximize patient recovery in a safe, efficient, and effective fashion.

Juvenile granulosa cell tumor in a 13-year-old girl with enchondromatosis (Ollier's disease): a case report.

Juvenile granulosa cell tumor (JGCT) of the ovary has been reported to occur rarely in conjunction with Ollier's disease. We report a case of a 13-year-old girl who was noted to have a large abdominal mass at the time of excision of a symptomatic enchondroma of the right femur. Subsequent laparotomy at a tertiary care children's medical center identified a JGCT confined to the right ovary. Review of the literature reveals eight previous cases of JGCT in patients with Ollier's disease. The pathophysiology and possible common causes of both disorders is discussed.

Synchronous wilms tumor and fibrolamellar hepatocellular carcinoma: report of a case.

Fibrolamellar hepatocellular carcinoma (FHCC) is a unique histologic variant of HCC that occurs in a younger subset of patients than classical HCC, and is associated with a better prognosis. Wilms tumor (WT) is a malignant embryonal neoplasm of the kidney and is one of the most common solid tumors of childhood, occurring at an estimated frequency of 1 in 8000 to 10,000 births. Although second malignant neoplasms (SMNs) following therapy for WTs have been reported in the liver, the coexistence of HCC and WT is extremely rare. We present the first report of a synchronous anaplastic WT and FHCC in a previously healthy 4-year-old girl. Despite the presence of focal immunohistochemical positivity for p53 in the WT, molecular analysis failed to reveal a germline or somatic p53 mutation, and was inconclusive in establishing a clonal relation between the two tumors.

K-ras and p53 mutations in the pathogenesis of classical and goblet cell carcinoids of the appendix.

BACKGROUND: Mutations in the K-ras oncogene and the p53 tumor suppressor gene are present in approximately 50% of colonic adenocarcinomas. Goblet cell carcinoids (GCCs) are uncommon neoplasms of the appendix that appear to be intermediate between carcinoid tumors and adenocarcinomas, both histologically and biologically. The current study was undertaken to examine the role of p53 and K-ras mutations in the pathogenesis of GCCs and typical carcinoids (TCs) of the appendix. METHODS: Archival materials from 22 GCCs and 18 TCs were analyzed. K-ras mutations in codons 12, 13, and 61 were studied by a polymerase chain reaction (PCR) based designed restriction fragment length polymorphism method using mismatched nested primers. Mutations in exons 5-8 of the p53 tumor suppressor gene were analyzed in 16 GCCs and 18 TCs by PCR and single-strand conformational polymorphism followed by direct sequencing. Immunostains for p53 and chromogranin were performed in all cases. RESULTS: K-ras mutations and nuclear accumulation of p53 by immunohistochemistry were not detected in any of the GCCs or TCs. p53 mutations were found in 4 of 16 GCCs (25%) and 8 of 18 TCs (44%). Immunoreactivity for chromogranin was seen in the vast majority of GCCs and TCs. CONCLUSIONS: p53 mutations appear to play a role in the pathogenesis of some GCCs and in approximately 50% of TCs of the appendix, whereas mutations in the K-ras oncogene do not appear to be important in the development of these tumors. The minimal cytologic atypia, low incidence of metastases, and lack of K-ras mutations in goblet cell appendiceal neoplasms suggest that they are variants of carcinoid tumors. Our findings lend support to the recommendation that the therapeutic guidelines applied to TCs of the appendix should be the same for GCCs.

Neurofibroma of the urinary bladder.

BACKGROUND: Neurofibroma of the urinary bladder is rare. Only isolated case reports have appeared. Information regarding the long term follow-up of patients with neurofibroma is limited. METHODS: The authors studied 4 cases of neurofibroma of the bladder diagnosed at Mayo Clinic from 1965 through 1990. Immunostains for S-100 protein, neurofilament protein, epithelial membrane antigen (EMA), cytokeratin (CAM 5.2; AE 1/3), Type IV collagen, MIB-1, and p53 protein were performed in all cases, as was Alcian blue at pH 2.5. The mean follow-up was 9.6 years (range, 2-18 years). RESULTS: The mean age at diagnosis was 17 years (range, 7-28 years); the male-to-female ratio was 1:1. All four patients exhibited physical stigmata of neurofibromatosis type 1. Clinical presentations included hematuria (one patient), irritative symptoms (two patients), and pelvic mass (one patient). Long term urinary complications included bladder atony (two patients), neurogenic bladder (one patient), and recurrent urinary tract infection with hematuria (one patient). Subsequently, two patients underwent partial cystectomy and one a complete cystectomy. Involvement of the bladder was generalized in all four cases. Three tumors were transmural, showing a diffuse and plexiform pattern of growth; in the fourth case, a superficial biopsy showed only diffuse submucosal growth with conspicuous pseudo-Meissnerian corpuscle formation. An Alcian blue positive, variably collagenized matrix was present in all cases. Tumor cells displayed immunoreactivity for S-100 protein and Type IV collagen in all cases. Neurofilament protein positive axons were evident in three cases; all other immunostains were negative. The mean MIB-1 labeling index was 3.2% (range, 0.9-7.3%). No malignant transformation was observed during a mean follow-up of 9.6 years. CONCLUSIONS: Neurofibroma of the bladder presents early in life, is of the plexiform type with a diffuse component, and usually occurs in the setting of generalized neurofibromatosis type 1 rather than as isolated visceral neurofibromatosis. Malignant transformation did not occur in any of these 4 patients during a mean follow-up time of 9.6 years.

Predicting the survival of bladder carcinoma patients treated with radical cystectomy.

BACKGROUND: Clinical outcomes vary for patients treated with radical cystectomy. The authors sought to identify factors associated with the survival of patients treated with radical cystectomy for urothelial carcinoma of the urinary bladder. METHODS: The authors studied 218 patients treated with radical cystectomy for urothelial carcinoma between 1980 to 1984. Patient ages ranged from 41 to 78 years (mean, 64 years). Using the 1997 TNM system, T classifications were Ta (17 patients), T1 (44), T2 (71), T3a (42), T3b (14), T4a (28), and T4b (2). Thirty-two patients had lymph node metastasis at the time of surgery. Histologic grade was determined according to the newly proposed World Health Organization and International Society of Urological Pathology grading system; tumor was low grade in 43 patients and high grade in 175. The male-to-female ratio was 4.9 to 1. The mean follow-up of patients still alive was 13.1 years (median, 13.8 years; range, 30 days to 18 years). Cox proportional hazards models were used to determine the impact of numerous clinical and pathologic findings on survival. RESULTS: Ten-year local recurrence free, distant metastasis free, cancer specific, and all-cause survival were 71%, 73%, 67%, and 41%, respectively. In univariate analysis, cancer size, T classification, and lymph node status were associated with distant metastasis free, cancer specific, and all-cause survival. Histologic grade and surgical margin status were significantly associated with worse cancer specific and all-cause survival, but not with distant metastasis free survival. In multivariate analysis, cancer size, margin status, T classification, and lymph node status were identified as significantly associated with cancer specific survival after adjustment for age and gender. CONCLUSIONS: Long term survival is achieved in a significant number of patients treated with radical cystectomy. In this study, patients with organ-confined (< or = pT2) and small size (< or = 3 cm) cancer had favorable 10-year distant metastasis free (93%) and cancer specific survival (88%) after cystectomy. Tumor size, margin status, extravesical involvement, and lymph node metastasis are important pathologic factors and should be considered as stratification variables in identifying patients for whom adjuvant chemotherapy should be evaluated in clinical trials.