Faculty Bibliography

Despite local therapy with curative intent, approximately 30% of men suffer from biochemical relapse. Though some of these PSA relapses are not life threatening, many men eventually progress to metastatic disease and die of prostate cancer. Local therapy is an option for some men, but many have progression of disease following local salvage attempts. One significant issue in this setting is the lack of reliable imaging biomarkers to guide the use of local salvage therapy, as the likely reason for a low cure rate is the presence of undetected micrometastatic disease outside of the prostate/prostate bed. Androgen deprivation therapy is a cornerstone of therapy in the salvage setting. While subsets may benefit in terms of delay in time to metastatic disease and/or death, research is ongoing to improve salvage systemic therapy. Prostate-specific membrane antigen (PSMA) is highly overexpressed by the majority of prostate cancers. While initial methods of exploiting PSMA's high and selective expression were suboptimal, additional work in both imaging and therapeutics is progressing. Salvage therapy and imaging modalities in this setting are briefly reviewed, and the rationale for PSMA-based systemic salvage radioimmunotherapy is described.

OBJECTIVES: Brain death is a clinical diagnosis often confirmed with supplementary tests. In this study, we examined the relationship between brain death and the partial pressure of brain tissue oxygen (PbtO(2)). We hypothesized that a sustained PbtO(2) of 0 is associated with brain death. METHODS: One hundred and twenty-six patients (Glasgow coma scale < or = 8, median age: 50 years) who underwent PbtO(2) monitoring were studied prospectively during a 2 year period in the neurointensive care unit at a university-based level I trauma center. PbtO(2), intracranial pressure (ICP), mean arterial pressure (MAP), cerebral perfusion pressure (CPP) and brain temperature (BT) were compared before and after the diagnosis of brain death. RESULTS: Six patients (median age: 52 years) experienced brain death. In these patients, PbtO(2) decreased toward 0 mmHg as ICP increased and CPP decreased. PbtO(2) reached 0 only when there was clinical evidence for brain death. During the subsequent 12 hours until the second brain death examination, PbtO(2) remained 0 mmHg and did not respond to oxygen challenge. In addition, TCD examination demonstrated a 'to and fro' pattern consistent with brain death and cerebral circulatory arrest. PbtO(2) of 0 mmHg was observed in five non-brain dead patients. These episodes were transient (>30 minutes) and responded to an oxygen challenge, directed treatment or catheter replacement. DISCUSSION: A sustained (>30 minutes) brain PbtO(2) of 0 is consistent with brain death. We suggest that a sustained 'zero' PbtO(2) may be used to determine when a brain death examination is appropriate in the pharmacologically suppressed patient

Metastatic disease to the brain occurs in a significant percentage of patients with cancer and can limit survival and worsen quality of life. Glucocorticoids and whole-brain radiation therapy (WBRT) have been the mainstay of intracranial treatments, while craniotomy for tumor resection has been the standard local therapy. In the last few years however, stereotactic radiosurgery (SRS) has emerged as an alternative form of local therapy. Studies completed over the past decade have helped to define the role of SRS. The authors review the evolution of the techniques used and the indications for SRS use to treat brain metastases. Stereotactic radiosurgery, compared with craniotomy, is a powerful local treatment modality especially useful for small, multiple, and deep metastases, and it is usually combined with WBRT for better regional control

BACKGROUND: The Fisher grade (FG) is widely used to predict cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). We revisited the grading scale to determine its validity in the era of modern management. METHODS: We retrospectively reviewed the records of 134 patients with SAH. The amount and distribution of subarachnoid blood on admission computed tomography (CT) scan was quantified according to the FG and compared with development of symptomatic vasospasm. RESULTS: We reviewed 134 patients (median age, 54) who presented with aneurysmal SAH. Six (5%) were FG 1, 34 (25%) were FG 2, 25 (19%) were FG 3, and 69 (51%) were FG 4. Symptomatic vasospasm developed in no (0%) FG 1, 8 (24%) FG 2, 7 (28 %) FG 3, and 13 (19%) FG 4 patients (28 of 134 total patients; 21%). Development of symptomatic vasospasm was not associated with admission FG, Hunt and Hess grade, age, sex, or location of blood on presenting CT scan. Elevated transcranial Doppler blood flow velocity was associated with blood in the basal cisterns (P = .0047), lateral ventricles (P = .026), or blood in any ventricle (P = .04). Postoperative angiograms were obtained in 57 patients; moderate to severe vasospasm was observed in 5 (15%) FG 2, 6 (24%) FG 3, and 14 (20%) FG 4 patients. Twenty patients (71%) with symptomatic vasospasm had moderate or severe angiographic vasospasm. Angiographic vasospasm was associated with intraventricular blood (P = .054) but not with FG. CONCLUSIONS: Symptomatic vasospasm occurred in 21% of cases. The FG correlated with symptomatic vasospasm in only half the patients. A new predictive CT grading scale for vasospasm may be necessary

Cognitive deficits persist in patients who survive traumatic brain injury (TBI). Lateral fluid percussion brain injury in the mouse, a model of human TBI, results in hippocampal-dependent cognitive impairment, similar to retrograde amnesia often associated with TBI. To identify potential substrates of the cognitive impairment, we evaluated regional neuronal loss, regional hippocampal excitability and inhibitory synaptic transmission. Design-based stereology demonstrated an approximate 40% loss of neurons through all subregions of the hippocampus following injury compared with sham. Input/output curves recorded in slices of injured brain demonstrated increased net synaptic efficacy in the dentate gyrus in concert with decreased net synaptic efficacy and excitatory postsynaptic potential-spike relationship in area CA1 compared with sham slices. Pharmacological agents modulating inhibitory transmission partially restored regional injury-induced alterations in net synaptic efficacy. Both evoked and spontaneous miniature inhibitory postsynaptic currents (mIPSCs) recorded in surviving dentate granule neurons were smaller and less frequent in injured brains than in uninjured brains. Conversely, both evoked and spontaneous mIPSCs recorded in surviving area CA1 pyramidal neurons were larger in injured brains than in uninjured brains. Together, these alterations suggest that regional hippocampal function is altered in the injured brain. This study demonstrates for the first time that brain injury selectively disrupts hippocampal function by causing uniform neuronal loss, inhibitory synaptic dysfunction, and regional, but opposing, shifts in circuit excitability. These changes may contribute to the cognitive impairments that result from brain injury

Immediate breast reconstruction for patients with early-stage disease is well established. This study evaluates a consecutive series of 22 patients with locally advanced disease (stage IIB or III) who underwent mastectomy and immediate breast reconstruction. All patients received several cycles of neoadjuvant chemotherapy (average, 3.5 cycles) followed by completion of chemotherapy beginning approximately 3 weeks following surgery. The perioperative morbidity was 14% and no patient suffered a delay in the resumption of chemotherapy. Patients have been particularly grateful about being offered reconstruction in this setting. Our preliminary results with this technique have been encouraging and further study is warranted.