Two-year Patient Survival Rates Research Articles

Assessment of two-year survival rate after acute myocardial infarction in patients with impaired carbohydrate metabolism during novel coronavirus infection pandemic

Relevance. There are limited data on the long-term outcomes of patients with myocardial infarction (MI) and impaired glucose tolerance (IGT) during the novel coronavirus disease (COVID-19) pandemic in 2020.
 Objective. To assess the 24-month survival rate among patients with IGT and previous myocardial infarction in 2020 during the COVID-19 pandemic compared to the same period in 2019.
 Materials and methods. We assessed the two-year survival rate of patients with MI and IGT from 10/1/2020 to12/10/2020 during the indirect influence of the pandemic compared to the same period in pre-pandemic 2019. The study was single-center, retrospective.
 Results. 179 persons in 2020 and 261 persons in 2019 with MI and IGT applied to a regional center to perform percutaneous coronary intervention (PCI center). There was an increase in mortality from MI and IGT from 4.1 % in 2019 to 9.9 % (p = 0.04) in the “pandemic” year of 2020. The relapse-free survival of patients was analyzed using the Kaplan – Meier curve method. By the end of the first year in 2020, 82.1 % of patients remained from the original, and in 2019 – 88.1 %, (p = 0.001), at the end of the 24-month observation period – 78.2 % among patients with MI in 2020 and 83.5 % in 2019, (p = 0.0015).
 Conclusions. A retrospective analysis of cases with MI and IGT during a pandemic in Russia showed the worst prognoses for the two-year survival rate among patients, more severe heart attacks with increased number of complications.

Long-term survival of patients with cerebrovascular accident in different age groups in the REGION-M registry

Aim. To study the two-year survival rate of patients with cerebrovascular accident (CVA) in different age groups.Material and methods. The outpatient part of the REGION-M registry included 684 patients assigned to the City Polyclinic № 64 in Moscow, discharged from the F. I. Inozemtsev City Clinical Hospital (Moscow) in the period from January 1, 2012 to April 30, 2017 with a confirmed diagnosis of stroke or transient ischemic attack. All patients were divided into 5 age groups: group 1 — from 18 to 50 years old (n=72 (10,5%)), group 2 — from 51 to 60 years old (n=122 (17,8%)), group 3 — from 61 to 70 years old (n=156 (22,8%)), group 4 — from 71 to 80 years old (n=185 (27,0%)) and group 5 — 81 years and above (n=149 (21,8%)). Patient survival was assessed after 2 years of follow-up.Results. The mortality rate of patients during the follow-up period significantly increased with age as follows: in patients of 18-50 years old — 4%, 51-60 years old — 9,8%, 61-70 years old — 23,7%, 71-80 years old — 34%, 81-100 years old — 55% (p<0,0001). The relative death risk was 2,3 in group 2 (NA), 6,8 in group 3 (p<0,001), 9,8 in group 4 (p<0,0001) and 18,5 in group 5 (p<0,0001) compared with group 1. With increasing age in the study cohort, the proportion of women increased as follows: from 47,2% in group 1 to 77,9% in group 5 (p<0,0001). However, mortality among men and women in the groups did not differ. Patients in older age groups were more likely to have comorbidities and disability before the CVA. With increasing age, ischemic stroke was significantly more common and transient ischemic attack was less common (p<0,001).Conclusion. Mortality of patients who underwent stroke was significantly higher in older age groups and did not differ among men and women.

Long-term survival of patients with various types of cerebrovascular accident: data from the outpatient part of the REGION-M registry

Aim. To study the two-year survival rate of patients with various types of cerebrovascular accident according to the outpatient part of the REGION-M registry.Material and methods. The outpatient part of the REGION-M registry included 684 patients assigned to the City Polyclinic № 64, discharged from the F. I. Inozemtsev City Clinical Hospital (Moscow) in the period from January 1, 2012 to April 30, 2017 with a confirmed diagnosis of stroke or transient ischemic attack (TIA). Of these, 514 (75,1%) patients had an ischemic stroke, 52 (7,6%) — a hemorrhagic stroke, and 118 (17,2%) — a TIA.Results. The lowest two-year mortality (11%) was observed in patients who underwent TIA (p<0,001) compared with ischemic and hemorrhagic stroke. The relative risk of death for ischemic stroke was 2,0 (95% confidence interval (CI): 1,13-3,55) (p<0,05), and for hemorrhagic stroke — 2,51 (95% CI: 1, 22-5,15) (p<0,05) relative to patients with TIA. Mortality in patients with ischemic or hemorrhagic stroke did not differ significantly — 32,3 and 36,6% (p>0,05). The mean age of patients who underwent TIA was significantly less than the age of patients with hemorrhagic or ischemic stroke. With increasing age, the survival of patients significantly worsened in all types of strokes. In addition, multivariate analysis adjusted for age showed remained significant effect of the stroke type on survival as follows: the relative risk of death for ischemic and hemorrhagic stroke was 1,99 (95% CI: 1,12-3,53) (p<0,05) and 2,45 (95% CI: 1,19-5,02) (p<0,05).Conclusion. Mortality in patients with stroke was significantly lower after TIA than in any type of stroke and did not differ between subgroups of patients with ischemic and hemorrhagic stroke.

Incidence of Acute Kidney Injury and Risk Factors of Prognosis in Patients with Acute Stanford Type A Aortic Dissection.

We aimed to investigate the prognosis and impact of postoperative acute kidney injury (AKI) in acute Stanford type A aortic dissection (ATAAD) patients, and to analyze the predictors of short- and medium-term survival. A total of 192 patients who underwent ATAAD surgery were included between May 2014 and May 2019. Perioperative data of these patients were analyzed. All of the discharged patients were followed up for 2 years. Postoperative AKI was identified in 43 of 192 patients (22.4%). The two-year survival rate of patients with AKI after discharge was 88.2% and that without AKI was 97.2%.The difference was statistically significant (χ2 = 5.355, log-rank P = 0.021). Cox hazards regression showed that age (hazard ratio [HR], 1.070; P = 0.002), cardiopulmonary bypass (CPB) time (HR, 1.026; P = 0.026), postoperative AKI (HR, 3.681; P = 0.003), and red blood cell transfusion (HR, 1.548; P = 0.001) were independent risk factors for the short- and medium-term total mortality of ATAAD patients. The incidence of postoperative AKI is high in ATAAD, and the mortality of patients with AKI increases significantly within 2 years. Age, CPB time, and red blood cell transfusion were also independent risk factors for short-and medium-term prognoses.

Effect of Fibroblast Growth Factor-23 (FGF-23) on Two-Year Mortality Rate in Chronic Kidney Disease Patients With Hemodialysis

Introduction
 Chronic kidney disease (CKD) is a global problem with increasing prevalence, poor prognosis, and high costs. Most deaths of CKD patients with hemodialysis (HD) is cardiovascular disorders. One of risk factors related to cardiovascular disorder is Fibroblast Growth Factor-23 (FGF-23). FGF-23 level is associated with increased mortality in CKD patients with HD.
 Aim & Objectives
 The aim of this study is to show the effect of Fibroblast Growth Factor-23 (FGF-23 on two year mortality rate in chronic kidney disease patients with hemodialysis.
 Materials and Method
 This retro-prospective mixcohort study with survival analysis obtained data from medical records of CKD patients undergoing HD at the Rasyidah Renal Hospital in the first week of January 2018. Patients were followed up next two years until 31st of December 2019. Kaplan Meier analysis was used to determine the effect of independent variables on dependent variable that was two years mortality, multivariate cox regression analysis to determine the dominant factor and magnitude of the association between independent variable and dependent variable. P-value <0.05 indicates a significant association.
 Result
 Kaplan Meier curve showed significant effect of FGF-23 level and Diabetes Mellitus on a two-year survival rate of patients (p = 0.01 and p = 0.04). Based on cox regression multivariate analysis, it was found patients with FGF-23 levels> 365ng/ml had a risk of 3.53 (CI95% 1,104-11,337) times more than group of patients with FGF-23 ≤ 365ng/ml while the presence of diabetes mellitus was risk factor on mortality with HR 3.71 (CI 1,279-10,796).
 Conclusion
 Statistically, FGF-23 level> 365 ng/ml is dominant factor that significantly influences 2-year mortality rate of CKD patients with HD other than Diabetes Mellitus.
 Key Words: Fibroblast Growth Factor, Chronic kidney disease on Hemodialysis, Mortality

Targeted Delivery of Liposomal Temozolomide Enhanced Anti-Glioblastoma Efficacy through Ultrasound-Mediated Blood-Brain Barrier Opening.

Glioblastoma (GBM) is the commonest form of primary brain tumor in the central nervous system, with median survival below 15 months and only a 25% two-year survival rate for patients. One of the major clinical challenges in treating GBM is the presence of the blood–brain barrier (BBB), which greatly limits the availability of therapeutic drugs to the tumor. Ultrasound-mediated BBB opening provides a promising approach to help deliver drugs to brain tumors. The use of temozolomide (TMZ) in the clinical treatment of GBM has been shown to be able to increase survival in patients with GBM, but this improvement is still trivial. In this study, we developed a liposomal temozolomide formulation (TMZ-lipo) and locally delivered these nanoparticles into GBM through ultrasound-mediated BBB opening technology, significantly suppressing tumor growth and prolonging tumor-bearing animal survival. No significant side effects were observed in comparison with control rats. Our study provides a novel strategy to improve the efficacy of TMZ against GBM.

Adherence to Attendance at Outpatient Clinic and Longterm Survival of Patients after Stroke in Outpatient Setting: the Data of REGION-M Registry

Aim. Assess the two-year survival rate of patients who have undergone acute cerebral circulation disorder, depending on their commitment to visiting the district polyclinic before and after discharge from the hospital.Material and methods. The outpatient part of the REGION-M register included 684 patients attached to the Moscow City Polyclinic №64, discharged from the Moscow City Clinical Hospital n.a. F.I. Inozemtsev of from 01.01.2012 to 04.30.2017 with a confirmed diagnosis of acute cerebral circulation disorder (cerebral stroke / transient ischemic attack).Results. Of the entire cohort, 83.2% of patients and 84.2% after hospital discharge attended the clinic during the year before the development of reference acute cerebral circulation disorder. Patients who attended the clinic before and after the reference stroke were older, more likely to have diabetes, comorbid disease and disability. For 22 months of follow-up, mortality was 28.8% (197 out of 684 people). Among those who applied and did not apply to the clinic before the reference acute cerebral circulation disorder, the difference in mortality tended to be reliable (27.4% versus 35.7%, p <0.1), while mortality was almost twice as low among patients who applied to the clinic at least 1 time after discharge (25.7%) than among patients who did not apply after discharge - 45.4%, p<0.0001. When adjusting for sex and age (the relative risk of death for them was 1.009, 95% confidence interval 1.005-1.01 2, p<0.0001 ), the statistical validity of reducing the risk of death was maintained when patients were committed to visiting the clinic after discharge - the relative risk of death 0.366 (95% confidence interval 0.269-0.500, p<0.0001 ).Conclusion. Lower mortality among those who visited the district polyclinic after undergoing stroke confirms the important role of medical observation in the posthospital period. At the same time, there is a reserve in improving the long-term prognosis of the lives of patients who have suffered a cerebral stroke or transient ischemic attack, due to greater coverage of patients with medical supervision in the clinic.

The value of intravoxel incoherent motion imaging in predicting the survival of patients with astrocytoma.

The evaluation of the prognosis of gliomas may have great value in individualized treatment. To evaluate the value of intravoxel incoherent motion (IVIM) in predicting the survival of patients with astrocytoma and comparing it to apparent diffusion coefficients (ADC). Sixty patients with pathologically confirmed cerebral astrocytomas underwent IVIM scans before any treatment was performed. Patients were divided into death group and survival group according to a two-year follow-up. ADC and quantitative parameters of IVIM including D, D*, and f were measured. Independent sample t test was used to compare the two groups of parameters. The accuracy of each parameter for two-year survival rate was analyzed by receiver operating characteristic (ROC) curve and Kaplan-Meier survival curves. The correlation between quantitative parameters and survival days was analyzed by Pearson correlation analysis. The ADC, D*, and f values were statistically significant different between the death and the survival groups (P < 0.05). The AUC of the ADC, D*, and f were 0.811, 0.858, and 0.892, respectively. The ADC cut-off value of 0.668 × 10-3 mm2/s corresponded to 82.6% sensitivity and 73% specificity. The D* cut-off value of 3.913 × 10-3 mm2/s corresponded to 78.4% sensitivity and 87% specificity. The f cut-off value of 0.487 corresponded to 83.8% sensitivity and 87% specificity. Significant log rank test was performed for each parameter to predict overall survival (P < 0.05). There was a correlation between ADC (r = 0.625, P = 0.023), D* (r = -0.655, P = 0.012), f (r = -0.725, P = 0.000) and survival days. The D* and f values demonstrated great potential in predicting the two-year survival rate for patients with astrocytoma.

Abstract 3219: Targeting lipid metabolism and ER stress in renal cell carcinoma by englerin A

Abstract Renal cell carcinoma (RCC) is among the top ten most common forms of cancer and is the leading malignancy of the kidney. Clear cell renal carcinoma (cc-RCC), the most frequent type of RCC, is one of the most refractory cancers with an incidence that is on the rise. The two-year survival rate for patients with metastatic disease is under 20% despite approved targeted therapies. Hence, there is an urgent need to investigate novel agents. Screening of plant extracts in search of new anti-cancer agents resulted in the discovery of englerin A (EA), a guaiane sesquiterpene with potent cytotoxicity against RCC and a small subset of other cancers. Although a few cellular targets have been identified for EA, in most instances, modulation of these targets required concentrations of EA much higher than that required to kill tumor cells highly sensitive to EA. Hence, it is still not clear what mechanisms account for the cytotoxicity of EA in tumor cells highly sensitive to EA. Unlike any prior study, the current study used a systems biology approach to explore the mechanism(s) of action of EA. Metabolomics analyses were conducted after treatment of human RCC A498 cells with 100 nM EA for 24 and 48 h. Pathway analysis revealed that 88% of the metabolic disturbance associated with englerin A at 24 h was due to changes in lipid metabolism. In particular, among the top metabolites, several ceramides and glucosylceramides increased up to 18- and 178-fold, respectively. On the other hand, all sphingomyelins decreased up to 5.5-fold. Furthermore, EA induced depletion in phosphatidylcholine, phosphatidylglycerol, and phosphatidylethanolamine phospholipids. At 48 h of englerin A treatment, the main findings from pathway analysis were the accumulation of fatty acylcarnitine derivatives, purines, pyrimidines, and phosphatidyl serine phospholipids, as well as the depletion of reduced glutathione indicating dysfunctional mitochondria and oxidative stress. Moreover, microarray analyses determined that EA (100 nM) induced ER stress signaling and an acute inflammatory response including interferon signaling, likely due to the generation of ceramides which were toxic to both A498 and UO-31 renal cancer cells. Quantitative PCR and Western Blot analyses confirmed that EA induced both the unfolded protein and acute inflammatory response. Furthermore, fluorescence confocal microscopy revealed that EA at 25 nM disrupted the morphology of the ER confirming the deleterious effect of EA on the ER. Collectively, our findings suggest that cc-RCC is highly sensitive to disruptions in lipid metabolism and ER stress and that these vulnerabilities can be targeted for the treatment of cc-RCC and possibly other lipid storing cancers. Furthermore, our results also suggest that ceramides may be a mediator of some of the actions of EA. Lastly, the acute inflammatory response induced by EA may mediate anti-tumor immunity. Note: This abstract was not presented at the meeting. Citation Format: Ayse Batova, Diego Altomare, Kim E. Creek, Robert K. Naviaux, Lin Wang, Kefeng Li, Erica Green, Richard Williams, Jane C. Naviaux, Mitchell Diccianni, Alice L. Yu. Targeting lipid metabolism and ER stress in renal cell carcinoma by englerin A [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3219. doi:10.1158/1538-7445.AM2017-3219

Telomerase activity in non-small cell lung cancer.

IntroductionHigh telomerase activity has been detected in the majority of malignant neoplasms including lung cancer. The purpose of the study was to attempt to use telomerase activity as a prognostic factor in patients with non-small cell lung cancer (NSCLC).Material and methodsTelomerase activity was analyzed in 47 tissue specimens taken from patients with NSCLC. The control group consisted of 30 specimens of non-cancerous lung parenchyma. Telomerase activity was measured by means of the telomeric repeat amplification protocol (TRAP).ResultsTelomerase activity in the neoplastic tissue was significantly higher than in the lung parenchyma that was free from neoplastic infiltration. There was no significant association between telomerase activity and age, gender, tobacco smoking, histological type of the tumor, or staging (pTNM). No association was found between the level of telomerase activity in NSCLC specimens and the two-year survival rate of patients (p = 0.326). A higher level of telomerase activity in poorly differentiated tumors (G3) as compared to moderately differentiated tumors (G2) was detected (p = 0.008). A positive association was identified between telomerase activity in pulmonary parenchyma free from tumor infiltration and the presence of leukocyte infiltration (p = 0.0001).ConclusionsNo association was found between the level of telomerase activity in NSCLC specimens and the two-year survival rate of patients. The study has revealed a positive association between telomerase activity and the grade of differentiation (G) in NSCLC.

Adoptive immunotherapy for non-small cell lung cancer by NK and cytotoxic T lymphocytes mixed effector cells: retrospective clinical observation.

The objective of the current study was to retrospectively investigate the efficacy of adaptive transfer of natural killer (NK) and cytotoxic T lymphocytes mixed effector (NKTm) cells in non-small cell lung cancer (NSCLC) patients in comparison to a control group of NSCLC patients. NKTm cells were obtained by ex vivo expansion of peripheral blood mononuclear cells (PBMCs) of patients followed with phenotype determination. Primary end point was overall survival (OS). Ex vivo expansion caused significant enrichment of CD3(+), CD3(+)CD8(+), CD45RO(+), CD25(+), CD29(+) and CD3(+)CD16(+)/CD56(+) cells (P<0.05). The OS of the immunotherapy group was significantly longer than that of the control group and the risk of death decreased by 43.8% (31.1 months vs 18.1 months, P=0.008, HR=0.562, 95% CI 0.367-0.860). Two-year survival rate of patients in the immunotherapy group was better than in the control group (62.95% vs 35.44%, P<0.05). Gender, clinical stage, application of TKI, number of chemotherapy cycle, and application of NKTm immunotherapy were independent prognostic factors for NSCLC patients. The OS in subgroups of males, <60 years age, clinical stage IIIb+IV, no brain metastases, without radiotherapy, chemotherapy of >6 cycles, no application of TKI and TKI invalid was prolonged after NKTm cellular immunotherapy (P<0.05). Ex vivo expansion of NKTm cells was effective and had no adverse safety concerns, thus highlight that adaptive transfer of NKTm cells may prolong the OS of NSCLC patients and increase 2 year survival rate.

Qualitative analysis of Adenomatous Polyposis Coli promoter: Hypermethylation, engagement and effects on survival of patients with esophageal cancer in a high risk region of the world, a potential molecular marker

BackgroundSquamous cell carcinoma of esophagus (SCCE) occurs at a high incidence rate in certain parts of the world. This feature necessitates that different aspects of the disease and in particular genetic characteristics be investigated in such regions. In addition, such investigations might lead to achievement of molecular markers helpful for early detection, successful treatment and follow up of the disease. Adenomatous Polyposis Coli (APC) promoter hypermethylation has been shown to be a suitable marker for both serum and solid tumors of adenocarcinoma of esophagus. We investigated the status of APC promoter hypermethylation in Iranian patients, compared the results with the former studies, and evaluated its applicability as a candidate molecular marker by examining association between survival of SCCE patients and APC promoter methylation.MethodsFor evaluating the status of APC promoter hypermethylation and its association with SCCE, a qualitative methylation specific PCR (MSP) was used. DNA was extracted and digested with an appropriate restriction enzyme, treated with sodium bisulfite in agarose beads and amplified in two-step PCR reaction by applying either methylated or unmethylated promoter specific primers. Universally methylated DNA and methylase treated blood DNA of healthy donors were used as positive controls as well. Survival of patients was followed up for two years after treatment and survival rate of patients with methylated APC promoter was compared with that of unmethylated patients.ResultsAssessment of APC promoter methylation revealed that normal tissues were unmethylated, while twenty out of forty five (44.4%) tumor tissues were hypermethylated either in one or both alleles of APC. Among the tissues in which methylation was detected, seven were hypermethylated in both alleles while the other thirteen were hypermethylated in one of the two alleles of APC. Analyzing two-year survival rate of patients with respect to promoter hypermethylation showed a lower rate of survival for patients with methylated APC promoter following their treatment. Further investigation into the association between promoter hypermethylation and tumor differentiation status indicated that patients with well differentiated tumors were more likely to develop promoter hypermethylation.ConclusionObserving similar level of APC promoter hypermethylation in patients with SCCE in this high risk region and comparing it with other parts of the world could support the hypothesis that a common molecular mechanism might be involved in tumorigenesis of SCCE. In addition, the higher rate of two-year survival for patients with unmethylated APC promoter as well as its relationship with tumor differentiation would suggest that this tumor suppressor could be an appropriate candidate molecular marker for evaluating tumor malignancy and predicting survival of patients subsequent to treatment.

Liver and Kidney Transplantation for Polycystic Liver and Kidney-Renal Function and Outcome

Polycystic liver disease (PLD) is a rare disorder frequently associated with polycystic kidney disease (PKD). Transplantation is a treatment option for these patients. Because of preservation of hepatic function in these patients, liver transplantation is not routinely utilized. We report a large series of PLD patients and their outcomes following liver and kidney transplantation. Fourteen patients underwent orthotopic liver transplantation (OLTx) for PLD between 1987 and 2003. Twelve patients had PKD combined with PLD. Nine patients received only liver transplantation. Five patients had combined liver and kidney transplantation. Thirteen patients (93%) survived for at least one year following liver transplantation. Two out of eight patients who received solitary liver transplantation later required kidney transplantation. Pretransplant glomerular filtration rate (GFR) in patients with PKD was 75.8+/-25.4 ml/min/1.73 m. One year later, GFR was 37.2+/-8.3 ml/min/1.73 m. Kaplan-Meier analysis showed that one- and two-year graft survival for combined liver and kidney transplantation was 80% (n=5), whereas graft survival for solitary liver transplantation was 100% (n=9). Mean survival of patients who had combined liver and kidney transplantation was 46.7+/-54.2 months (n=5), whereas the mean survival for solitary liver transplant patients was 80.4+/-68.6 months (n=9) (P=0.36). Transplantation is an excellent option for PLD with dramatic improvement in quality of life and acceptable morbidity. For combined liver and kidney transplantation one- and two-year patient survival rates were similar to combined transplantation for other indications. For patients with acceptable renal function at time of transplantation, solitary liver transplantation has an excellent outcome.

Results of Surgical Resection for Progression of Brain Metastases Previously Treatedby Gamma Knife Radiosurgery

To determine treatment outcome after surgical resection for progressive brain metastases after gamma knife radiosurgery (GKR) and to explore the role of dynamic contrast agent-enhanced perfusion magnetic resonance imaging (MRI) and proton spectroscopic MRI studies (MRS/P) in predicting pathological findings. Between 1997 and 2002, 32 patients underwent surgical resection for suspected progression of brain metastases from a cohort of 245 patients with brain metastases treated with GKR. Postradiosurgery MRI surveillance was performed at 6 and 12 weeks, and then every 12 weeks after GKR. In some cases, additional MRI scanning with spectroscopy or perfusion (MRS/P) was used to aid differentiation of radiation change from tumor progression. The decision to perform neurosurgical resection was based on MRI or clinical evidence of lesion progression among patients with a Karnofsky performance score of 60 or more and absent or stable systemic disease. Thirteen percent (32 out of 245) of patients and 6% (38 out of 611) of lesions required surgical resection after GKR. The median time from GKR to surgical resection was 8.6 months (range, 1.7-27.1 mo). The 6-, 12-, and 24-month actuarial survival from time of GKR was 97, 78, and 47% for the resected patients and 65, 40, and 19% for the nonresected patients (P < 0.0001). The two-year survival rate of patients requiring two resections after GKR was 100% compared with 39% for patients undergoing one resection (P = 0.02). The median survival of resected patients was 27.2 months (range, 7.0-72.5 mo) from the diagnosis of brain metastases, 19.9 months (range, 5.0-60.7 mo) from GKR, and 8.9 months (range, 0.2-53.1 mo) from surgical resection. Tumor was found in 90% of resected specimens and necrosis alone in 10%. MRS/P studies were performed in 15 resected patients. Overall, MRS/P predicted tumor in 11 lesions, confirmed pathologically in nine lesions, and necrosis alone was found in two. The MRS/P predicted necrosis alone in three, whereas pathology revealed viable tumor in two and necrosis in one lesion. Surgical intervention of progressive brain metastases after GKR in selected patients leads to a meaningful improvement in survival rates. Further studies are necessary to determine the role of MRS/P in the postradiosurgery surveillance of brain metastases.

Influence of Peritoneal Transport Rate, Inflammation, and Fluid Removal on Nutritional Status and Clinical Outcome in Prevalent Peritoneal Dialysis Patients

To evaluate the possible associations between peritoneal transport rate (PTR), fluid removal, inflammation, and nutritional status in patients treated with peritoneal dialysis (PD) for more than 6 months, and the impact of these factors on subsequent patient survival. A prospective study of 82 PD patients (48 males) that had been treated with PD more than 6 months. Based on the dialysate-to-plasma creatinine ratio at 4 hours of dwell (D/P Cr; mean +/- 1 SD), the patients were classified as having a high (H), high-average (HA), low-average (LA), or low (L) PTR. Single PD unit in a university hospital. The PTR, evaluation of adequacy of dialysis and nutritional status, and biochemical analyses were assessed at 10.8 +/- 2.8 months after the start of PD. Compared to L and LA (L/LA) transporters, H and HA (H/HA) transporters had increased dialysate protein loss, glucose absorption from dialysate, and peritoneal creatinine clearance (CCr), and decreased night ultrafiltration volume and total Kt/V urea. However, nutritional variables, 24-hour total fluid removal (TFR), total CCr, and residual renal function were not significantly different between the two groups. The 24-hour TFR correlated significantly with D/P Cr (rho = -0.25), mean arterial pressure (rho = -0.23), serum albumin (rho = 0.25), normalized protein equivalent of total nitrogen appearance (rho = 0.34), lean body mass (LBM) calculated from creatinine kinetics (rho = 0.41), total Kt/N urea (rho = 0.42), and total CCr (rho = 0.30). The group with serum C-reactive protein (sCRP) > or = 10 mg/L had a higher proportion of patients with reduced (< 1,000 mL) TFR compared to the group with sCRP < 10 mg/L (38% vs 16%, p = 0.04). Two-year patient survival rates from the time of the assessment were not different between the different transport groups (78% vs 73% for H/HA and L/LA, p = 0.99). Upon Cox proportional hazards multivariate analysis, age and high sCRP were independent predictors of mortality. This study shows that, in a selected group of prevalent PD patients assessed after more than 6 months of PD therapy, (1) inflammation was an independent predictor for mortality; (2) reduced TFR was associated with impaired nutritional status, decreased small solute clearance, and inflammation; and (3) peritoneal transport status was not significantly associated with nutritional status and was not associated with subsequent patient survival. These results indicate that a high peritoneal solute transport rate, as such, should not be regarded as a relative contraindication for PD. Instead, the results suggest that more attention should be given to inflammation and inadequate fluid removal as predictors of mortality in PD patients.

Patterns of care for metastatic carcinoma of the prostate gland: results of the American College of Surgeons' patient care evaluation study.

The annual incidence of prostate cancer more than doubled between 1984 and 1990, increasing from an estimated 76 000-200 000 cases respectively. Part of this increase may have been the result of increased detection. This study utilizes data from an American College of Surgeons Patient Care Evaluation (PCE) study to report on changes in the management of metastatic disease. Approximately 2000 hospitals were invited to submit data on a standard collection form designed by a multidisciplinary committee of specialists. Data were received from 730 hospitals on 14 716 patients with newly diagnosed cancer of the prostate in 1984, and from 1035 hospitals for 23 214 patients in 1990. Between 1984 and 1990 there was a decrease in the percentage of reported patients diagnosed with Stage IV disease, falling from 25.3-21.2%. The number of patients receiving a prostate specific antigen (PSA) test increased from 6.3-74.8% and the proportion of abnormal PSA results increased from 82-92.7%. The proportion of patients diagnosed by transurethral resection of the prostate (TURP) and perineal biopsy decreased, while an increase was noted in the proportion of men diagnosed by transrectal biopsy and transrectal ultrasound (TRUS). Treatment by orchiectomy alone increased from 31.8-40.7% of patients, while the administration of exogenous hormone therapy alone declined from 22.3-14.9% of patients. Two and five-year survival rates for the most common forms of therapy were 56.7% and 22.5% respectively for orchiectomy, 57% and 24.6% respectively for exogenous hormone therapy, and 50.3% and 23.5% respectively for no cancer directed therapy. Following a second course of therapy, the two-year survival rate for patients receiving a subsequent orchiectomy was 36.7 vs 17.8% for those receiving secondary exogenous hormone therapy. The percentage of patients diagnosed with Stage IV disease has decreased while prostate cancer diagnoses are being made more frequently utilizing the PSA test and TRUS biopsies. Hormone treatment remains the most common form of therapy with either orchiectomy or exogenous hormone therapy having higher survival rates than other common treatment modalities.

Splenectomy during primary and secondary cytoreductive surgery for epithelial ovarian carcinoma

Scarabelli C, Gallo A, Campagnutta E, Carbone A. Splenectomy during primary and secondary cytoreductive surgery for epithelial ovarian carcinoma. Int J Gynecol Cancer 1998; 8: 215–221. Splenectomy is occasionally indicated to achieve optimal cytoreduction during surgery for epithelial ovarian cancer. Between January 1989 and December 1996, 40 epithelial ovarian cancer patients underwent splenectomy: 14 patients during primary surgery and 26 during secondary cytoreductive surgery. Splenectomy was performed for tumor reduction in 34 patients (85 %) and for iatrogenic injury in six patients (15%). The spleen was removed because of parenchymal splenic metastases in nine patients (22.5 %), significant hilar and/or capsular disease in 10 patients (25 %), and perisplenic disease in 15 patients (37.5%). The histopathological diagnosis of the resected spleens showed microscopic hilar disease in four patients who had the spleen removed because of iatrogenic injury and no disease in only two patients. Splenectomy could be carried out with an acceptable morbidity. Left-sided pleural effusion was the most frequent complication. The estimated two-year survival rate for patients who underwent splenectomy during primary surgery with no residual disease and 1 year) recurrent disease.

A CLINICAL STUDY ON BILE DUCT CANCER OF THE HEPATIC HILAR REGION

This study was made on 20 operated cases (48.1 per cent) out of 41 cases of bile duct cancer at the hepatic hilar region at the department in the past 22 years. In this series (11 resected and 9 unresected) an absolute curative resection was achieved in 2 cases, a relative curative resection was achieved in 3 cases and 6 cases were non-curative resections. The main reason for non-curative resections was cancer infiltration. Most of the patients with non-curative resection died within 1 year, but one-year and two-year survival rates in resected cases were 81.8 per cent and 45.5 per cent respectively. Among Stage IV cases, the survival rate of resected cases was significantly higher than that of non-resected cases. In resected cases, most of the patients with tumor infiltration of the surgical margin died within 2 years, but the two-year survival rate of patients with tumor-free surgical margins was 75.0 per cent. A resected Stage IV patient with combined therapy survived for 3 years and 9 months. These results suggest that tumorfree surgical margin is necessary in order to improve the outcome of bile duct cancer at the hepatic hilar region and combined therapy may improve the outcome.

The 1991 Merck Frosst Award. Multidrug resistance in small cell lung cancer.

The two-year survival rate of patients with small cell lung cancer is less than 10%. The major reason for this poor outcome is the development of drug resistance. Panels of small cell lung cancer cell lines have been established, providing models for the study of drug resistance in this tumour. One such model is the doxorubicin-selected H69AR cell line. H69AR displays the typical multidrug resistance phenotype in that it is cross-resistant to anthracyclines, Vinca alkaloids (e.g., vinblastine) and epipodophyllotoxins (e.g., VP-16). However, H69AR cells do not overexpress P-glycoprotein, the membrane drug efflux pump frequently found on multidrug resistant cells. Some alterations in glutathione levels and associated enzyme activities were found but the data do not support the notion that enhanced drug detoxication is involved in H69AR cell resistance. Fewer drug-induced DNA strand breaks, reduced levels of topoisomerase II, and reduced formation of drug-stabilized DNA/topoisomerase II complexes were observed in H69AR cells. These data implicate topoisomerase II in the resistance phenotype of H69AR cells, but cannot explain H69AR cell resistance to the Vinca alkaloids, which do not have topoisomerase II as a target. Monoclonal antibodies against antigens overexpressed on H69AR cells have been derived and four have been characterized. Immunoscreening of an H69AR cDNA expression library has allowed the identification of one of these antigens as p36 (annexin II), a Ca2+/phospholipid binding protein. Chemosensitizers and novel xenobiotics have been examined for their ability to circumvent the drug resistance of H69AR cells. The limited success of these investigations suggests that innovative approaches may be required. In conclusion, the data obtained with H69AR and other models of small cell lung cancer indicate that multiple mechanisms contribute to drug resistance in this disease.