Magnetic resonance imaging and magnetic resonance angiography before postchemotherapy retroperitoneal lymph node dissection.

OBJECTIVES: Retroperitoneal lymph node dissection (RPLND) after primary chemotherapy is an accepted therapeutic approach for metastatic nonseminomatous germ cell testicular cancer. Because of the intense desmoplastic reaction and adherence to venous and arterial walls, accurate imaging of the retroperitoneal vasculature and its relation to residual tumor is essential. We report our experience with magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), including the recently developed technique of bolus-contrast MRA, in patients undergoing postchemotherapy RPLND. METHODS: Eighteen patients underwent MRI of the retroperitoneal region before RPLND. In addition to routine sequences, MRA was performed in 10 patients, including 8 with a three-dimensional technique using bolus intravenous MR contrast. Results were compared with intraoperative and pathologic findings. RESULTS: MRI and MRA provided detailed information on retroperitoneal vasculature and its relation to tumor, including multiple renal vessels (n = 5), duplex inferior vena cava (n = 1), left retroaortic renal vein (n = 2), and common iliac vein thrombus (n = 1). In all cases, bolus-contrast MRA provided unique information on the location and number of renal and lumbar arteries, in addition to information on the aorta and the mesenteric and iliac vessels. The origin and number of renal arteries were accurately identified in all patients by bolus-contrast MRA; 2 patients had supernumerary renal arteries discovered at RPLND that had not been identified on non-bolus-contrast MRI. CONCLUSIONS: Bolus-contrast three-dimensional MRA provides unique information on renal and lumbar vessels. The potential benefit of avoiding vascular injury during dissection should be prospectively evaluated.

Dissociation between bone resorption and bone formation in osteopenic transgenic mice.

Bone mass is maintained constant in vertebrates through bone remodeling (BR). BR is characterized by osteoclastic resorption of preexisting bone followed by de novo bone formation by osteoblasts. This sequence of events and the fact that bone mass remains constant in physiological situation lead to the assumption that resorption and formation are regulated by each other during BR. Recent evidence shows that cells of the osteoblastic lineage are involved in osteoclast differentiation. However, the existence of a functional link between the two activities, formation and resorption, has never been shown in vivo. To define the role of bone formation in the control of bone resorption, we generated an inducible osteoblast ablation mouse model. These mice developed a reversible osteopenia. Functional analyses showed that in the absence of bone formation, bone resorption continued to occur normally, leading to an osteoporosis of controllable severity, whose appearance could be prevented by an antiresorptive agent. This study establishes that bone formation and/or bone mass do not control the extent of bone resorption in vivo.

Combination chemotherapy for metastatic or locally advanced genitourinary squamous cell carcinoma: a phase II study of methotrexate, cisplatin and bleomycin.

PURPOSE: The prognosis of patients with advanced squamous cell carcinoma of genitourinary origin is poor. While single agent chemotherapy results mainly in partial responses of short duration, data on the efficacy of combination chemotherapy are extremely limited. We determined the response rate and toxicity of a combination of 3 of the most active agents, methotrexate, cisplatin and bleomycin, in patients with advanced genitourinary squamous cell carcinoma. MATERIALS AND METHODS: Patients with metastatic or locally advanced genitourinary squamous cell carcinoma were eligible for study. Treatment consisted of 200 mg./m.2 methotrexate on days 1, 15 and 22, and 20 mg./m.2 cisplatin and 10 mg./m.2 bleomycin on days 2 through 6 during a 28-day cycle. RESULTS: Of the 30 patients who enrolled in the trial 29 were evaluable for response. Objective response was achieved in 16 patients (55%, 95% confidence interval 36 to 72), 4 of whom achieved a complete response (14%). Median objective response duration was 4.7 months (range 1.9 to 39.5). Median survival of the entire group was 11.5 months (range 1.5 to 87.0). Of the patients 9 achieved disease-free status, including 6 following consolidation surgery or radiation therapy. Median survival of these 9 patients (34.4 months, range 9.6 to 87.0) was significantly greater (p = 0.0003) than that of patients who did not become disease-free (7.0 months, range 1.5 to 38.6). Grade III or IV hematological toxicity in 116 courses included neutropenia (13%) and thrombocytopenia (6%). Among 30 patients evaluable for toxicity serious nonhematological toxic effects included stomatitis (3%) and renal toxicity (7%). There was 1 death from neutropenic sepsis. CONCLUSIONS: Methotrexate, cisplatin and bleomycin combination chemotherapy for genitourinary squamous cell carcinoma results in a high but short lived overall response rate, and a low complete response rate with manageable toxicity. A multidisciplinary approach to achieve disease-free status may provide the best opportunity to effect survival and should be the focus of future trials.

Genomic organization, expression of the human CBFA1 gene, and evidence for an alternative splicing event affecting protein function.

The Cbfa1 gene, which encodes the transcription factor Osf2/Cbfa1 required for osteoblast differentiation in mouse and human, is mutated in cleidocranial dysplasia, a skeletal dysplasia. We describe here the isolation of the full-length human OSF2/CBFA1 cDNAs, the genomic organization of the entire CBFA1 gene, its expression, and the existence of an alternative splicing event. Nucleotide sequence analysis of the human and mouse OSF2/CBFA1 cDNAs showed a 98% homology in the coding sequence and 96% in the 5' untranslated (UTR) sequence. Analysis of CBFA1 genomic clones revealed that the 5' UTR sequence of the human OSF2/CBFA1 cDNA lies 75 kb upstream of the originally described 5' end of the gene. The existence of two OSF2/CBFA1 cDNAs is due to an alternative splicing event around exon 8 that affects the transcriptional activity of the protein. Northern blot analysis demonstrates that the expression of the human OSF2/CBFA1 gene is restricted to osteoblastic cells.

New approaches in the treatment of metastatic transitional-cell cancer of the bladder.

In recent years, chemotherapy of metastatic transitional-cell carcinoma of the bladder has advanced from the use of individual therapeutic agents, which has effected only rare responses, to the development of multi-agent regimens, which have greatly improved both partial and complete response rates, resulting in improved local care, palliation, and; perhaps, survival. However, because of the limited duration of response, frequent recurrences, and the significant proportion of patients with refractory disease, there have been only modest overall gains in long-term disease-free survival. These shortcomings have prompted investigation of alternative approaches to current combination chemotherapy regimens, including the use of hematopoietic growth factors and novel single-agent, multi-agent, and gene therapy protocols.

Treatment options for localized recurrence of prostate cancer following radiation therapy.

Patients with radioresistant clinically localized prostate cancer may be treated by various means. Although androgen ablation is relatively noninvasive, it cannot be considered a curative option. We believe that a subset of patients with locally recurrent prostate cancer without subclinical metastatic disease exists and would benefit from maximally aggressive local therapy. Salvage surgery may offer long-term cancer control, particularly when the tumor is organ-confined, but is a technically challenging operation with a high incidence of postoperative incontinence. Cryoablation of the prostate for postirradiation recurrence may offer a less invasive alternative to radical surgery, but its long-term efficacy remains to be fully determined. Each therapeutic option has its characteristic attendant morbidity and the choice of therapy for local recurrence should be made with informed consent after frank discussion between physician and patient. We propose the treatment algorithm shown in Figure 1 for the management of patients with suspected recurrence after radiation therapy with the caveat that individual therapeutic strategies must be patterned around individual patient needs.

Ureteral entrapment in the sacroiliac joint in pelvic trauma.

We describe a case of unilateral entrapment of the ureter in the sacroiliac joint of a patient who sustained blunt abdominal trauma resulting in fractures of the public rami and sacroiliac joint and multiple bladder perforations. The entrapment was discovered intraoperatively and released by external traction and reduction of the pelvic fractures. No ureteric damage was observed, and reimplantation was not necessary. The importance of evaluating the upper tracts for potential injury in patients with fractures of the bony pelvis and concomitant bladder rupture is emphasized.

Survival of men with clinically localized prostate cancer detected in the eighth decade of life.

We reviewed our experience with the management of men 70 to 79 years old with clinically localized prostate cancer to determine whether surgical candidates were likely to die of intercurrent disease soon after the disease was diagnosed. Of 101 men in the eighth decade of life who were surgical candidates by all criteria other than patient age 44 underwent radical prostatectomy, whereas 57 were managed by medical therapy including observation, radiation therapy and/or androgen deprivation. Five patients died in the surgical group at a median followup of 59 months, only 1 of whom died of intercurrent disease. Among 15 deaths in the medical group metastatic prostate cancer was the most common cause and all deaths from prostate cancer occurred more than 3 years after diagnosis. Survival for the surgical group was significantly better than that for the medical group during followup (p < 0.01 log-rank test). We conclude that men at our institution who underwent radical prostatectomy in the eighth decade of life did not frequently die of intercurrent disease, and experienced acceptable morbidity and mortality rates. We believe that men with localized prostate cancer should not be denied a radical operation based on age alone.

Recurrent transitional cell carcinoma in an ileal conduit treated by sandwich chemotherapy and surgical resection.

Recurrent transitional cell carcinoma in a ureteroileal conduit following radical cystectomy is rare. The prognosis for these patients is uniformly poor. We report on a patient with transitional cell carcinoma in an ileal conduit treated by chemotherapy and partial excision of the ileal conduit. He was without evidence of disease 4 1/2 years after completion of therapy.

Mitogenic response of osteoblast cells to prostate-specific antigen suggests an activation of latent TGF-beta and a proteolytic modulation of cell adhesion receptors.

During studies of mitogens in prostate, PSA quantities as low as 2.5 ng/mL caused cultured osteoblast cells to proliferate beyond controls (p = 0.05). Investigation of this novel mitogenicity suggested the use of several mechanisms by PSA, namely: 1) the activation of latent hTGF-beta in PC-3 conditioned medium, PSA treated conditioned medium stimulated DNA uptake in UMR-106 cells to 78% of acid treated conditioned medium, while DNA incorporation was less than controls with anti-hTGF-beta neutralizing IgG; and 2) the proteolytic modulation of cell surface receptors with temporary contact inhibition, PSA significantly stimulated cell detachment while hTGF-beta enhanced cell attachment of confluent Saos-2 cells above controls. Clinically, these results suggest that PSA may provide a mechanism for both tumor spread and the osteoblastic metastasis so common to prostate cancer.