2. Survival Impact of HER-2/Neu, Cox-2, Urokinase Plasminogen Activator (upa), Cytokeratin 17/5,6 and other Markers with Long-Term Outcome of Early Breast Cancer. Report from the British Columbia Tissue Micro-Array Project (BCTMAP)

Tumor samples are available from over 19,600 Stage I-III breast cancer patients treated according to evolving British Columbia guidelines from 1978 to 1990. A tissue mico-array (TMA) was constructed from 930 of these patients, all of whom participated in randomized or phase II studies. Outcome was defined as 20-year Breast Cancer specific Survival (BrCaSS), with events defined as Breast Ca death. Follow up was median 17.8 years (ranges 11–28). Multiple tumor markers were tested, and results correlated with 20-year BrCaSS for markers expressed versus non-expressed. No difference in BrCaSS was found for aromatase, integrin-linked kinase (ILK), IGF-1 and Topo-isomerase-2. The negative predictive value of IHC versus FISH and ACIS-IHC versus FISH was 96 and 97%, respectively. The positive predictive value of IHC versus FISH and ACIS-IHC versus FISH was 84 and 84%, respectively. All tests, with the exception of HER-2 FISH were done by IHC. Results of other markers (VEGF, ER/PgR, hypoxia markers, etc.), and an interactive multivariate analysis adjusting for conventional prognostic factors and for all above markers, are in progress. Conclusions 1. The TMA is a technique which provides opportunity for rapid screening of multiple genetic markers.2. Expression of Her-2/Neu, uPA, Cox-2 and Cytokeratin 17/5,6 (but not of Aromatase, ILK, TOPO-II and IGF-1) is associated with inferior BrCaSS.3. HER-2 determination by ACIS-IHC provides comparable results to IHC done manually (with a potential for more uniform reporting), and both provide comparable results to Her-2 assessment by FISH. ^** ACIS-IHC:IHC red by Automated Cell Image System (M.L.)     

Psychological responses of patients receiving a diagnosis of cancer.

BACKGROUND: Current recommendations on how to break bad news are primarily based on expert opinion. Little is known about the association between communication practices and patients' psychological response. PATIENTS AND METHODS: One-hundred and thirty-one patients with newly diagnosed melanoma were surveyed 4 months after the initial consultation at the Sydney Melanoma Unit regarding their communication experiences and their satisfaction with these experiences. They completed the Hospital Anxiety and Depression Scale (HADS) at this time, and 4 and 13 months later. RESULTS: Both patients' satisfaction with communication and their psychological morbidity were found to be associated with particular communication practices. Practices linked to lower anxiety included preparing the patient for a possible diagnosis of cancer; having the people wanted by the patient present to hear the diagnosis; giving the patient as much information about the diagnosis as desired; providing written information; presenting the information clearly; discussing the patient's questions the same day; talking about the patient's feelings; and being reassuring. Practices linked with lower levels of depression included using the word 'cancer'; discussing the severity of the situation, life expectancy and how the cancer might affect other aspects of life; and encouraging the patient to be involved in treatment decisions. CONCLUSIONS: This study provided preliminary evidence that communication strategies recommended in the literature produce positive patient outcomes. Further studies are needed which document actual communication.     

Renal physiology. Laparoscopic considerations

Oliguria is a recognized component of the physiologic effect of increased intra-abdominal or retroperitoneal pressure. The cause is multifactorial, emanating from vascular and parenchymal compression, and is associated with systemic hormonal effects. Ureteral obstruction does not play a significant role. These changes are pressure-dependent and are usually not apparent until pressures reach 15 mm Hg or more. This effect is not associated with any histologic pathology or evidence of renal tubular damage. After the release of the pneumoperitoneum or pneumoretroperitoneum, the renal function and urine output return to normal with no long-term sequelae, even in patients with pre-existing renal disease. The entire operative team must understand the physiologic effects of CO2 insufflation, which allows appropriate intraoperative monitoring and management and minimizes intraoperative and postoperative complications.     

Differential expression of the PSD-95 gene family in electrosensory neurons

The PSD-95 family of membrane-associated guanylate kinase (MAGUK) proteins are involved in the assembly and organization of neurotransmitter receptors at excitatory synapses in the vertebrate nervous system. We have isolated partial cDNAs for five PSD-95 family members from Apteronotus leptorhynchus brain RNA using a degenerate PCR method. The amino acid sequences deduced indicate that A. leptorhynchus neurons express homologues of the mammalian PSD-93, SAP-97, and SAP-102 MAGUKs and two homologues of mammalian PSD-95. In situ hybridization experiments have been carried out to localize the cellular expression of all five MAGUK mRNAs in the central nervous system of A. leptorhynchus. In the cerebellum the expression patterns are highly similar to patterns reported for mammalian cerebellum, suggesting an evolutionary conservation of the functional roles in this gene family. Cellular levels of expression of the PSD-95 MAGUK mRNAs and the NMDAR-1 mRNA were highly correlated in neurons of the dorsal forebrain but were not correlated in neurons of the electrosensory lateral line lobe (ELL) or the cerebellum. These results suggest that the expression of PSD-95 MAGUK genes in forebrain neurons may provide mechanisms for synaptic organization that are not shared by neurons in the ELL and cerebellum.     

Effect of hyperventilation on brain tissue oxygenation and cerebrovenous PO2 in rats

Previous studies have shown that cortical tissue oxygenation is impaired during hyperventilation. However, it is important to quantify the effect of hyperventilation on brain tissue PO(2) and cerebrovenous PO(2) simultaneously especially since cerebral venous oxygenation is often used to assess brain tissue oxygenation. The present study was designed to measure the sagittal sinus PO(2) (PvO(2)), brain tissue PO(2) in the thalamus (PtO(2)), and brain temperature (Bt) simultaneously during acute hyperventilation. Isoflurane-anesthetized rats were hyperventilated for 10 min during which time the arterial carbon dioxide tension (PaCO(2)) dropped from 40.3+4.9 mmHg to 23.5+2.8 mmHg. PtO(2) declined from 26.0+/-4.2 mmHg to 14.8+/-5.2 mmHg (P=0.004) while brain temperature decreased from 36.5+0.3 degrees C to 36.2+0.3 degrees C (P=0.02). However, PvO(2) and arterial blood pressure (BP) did not change during hyperventilation. The maintenance of PvO(2) when perfusion is thought to decline and PtO(2) decreases suggests that there may be a diffusion limitation, possibly due to selective perfusion. Therefore, cerebrovenous PO(2) may not give a good assessment of brain tissue oxygenation especially in conditions of acute hyperventilation, and deeper brain regions other than the cortex also show impaired tissue oxygenation following hyperventilation.     

Physiology of the lateral decubitus position and one-lung ventilation

OLV is most frequently utilized to provide a quiet field for the performance of many different surgical procedures. In some patients, severe hypoxemia may result, mandating the implementation of other therapies to provide adequate oxygenation. This paper has reviewed the physiological consequences of the lateral position that may contribute to the hypoxemia and the techniques we utilize at our institution for establishing OLV, maintaining OLV, and treating hypoxemia during OLV. Our technique is performed with the goal of maintaining adequate gas exchange and protecting the ventilated lung from potential overdistension and injury. It remains for future study to determine if the use of a lung protective strategy during intraoperative OLV offers any benefit to patients at risk for postoperative lung injury, such as those undergoing major lung resections.     

Long-term outcomes among localized prostate cancer survivors: health-related quality-of-life changes after radical prostatectomy, external radiation, and brachytherapy.

PURPOSE: We sought to elucidate long-term changes in health-related quality-of-life (HRQOL) outcomes by prospectively re-evaluating a well-characterized cohort of prostate cancer (PC) survivors 4 to 8 years after primary treatment. PATIENTS AND METHODS: Patients who had been evaluated previously at a median of 2.6 years after radical prostatectomy (RP), external radiation (three-dimensional conformal radiation therapy [3-D CRT]), or brachytherapy (BT) were recontacted at a median of 6.2 years after treatment. The clinical relevance of long-term HRQOL impairment among survivors was established by comparison with controls of similar age. Factors associated with HRQOL changes during this interval were evaluated. RESULTS: Of the 964 eligible men, 709 (73.5%) completed measurable questionnaires. In four domains (urinary irritative-obstructive, urinary incontinence, bowel, and sexual), significant HRQOL differences were detected for at least one of the therapy groups, compared with controls (all P < .05). During the 4-year interval, significant improvement was observed for the urinary irritative-obstructive (P < .0001) and bowel (P < .0001) domains among BT patients, whereas urinary incontinence HRQOL worsened for both the BT (P = .0017) and 3-D CRT (P = .0008) treatment groups. Overall sexual HRQOL deteriorated for the 3-D CRT cohort (P = .0017), as well as for controls (P = .0136). Among RP patients, significant HRQOL changes were not observed. CONCLUSION: During a 4-year interval from earlier to longer-term phases of PC treatment survivorship, sexual, urinary, and bowel dysfunction remain significant concerns among early-stage PC treatment survivors, compared with control men. Although postprostatectomy HRQOL remains relatively stable during this interval, disease-specific HRQOL continues to evolve among men treated with BT and 3-D CRT.