Graeme S. Steele

A prospective evaluation of hepatic resection for colorectal carcinoma metastases to the liver: Gastrointestinal Tumor Study Group protocol 6584

We report here the results of the first multiinstitutional prospective evaluation of patients considered to have potentially resectable hepatic metastases from colorectal carcinoma. One hundred fifty-six patients were enrolled from 15 institutions. Six patients were subsequently excluded. One hundred fifty patients underwent surgery and are evaluable for analysis (median follow-up time, 3.1 years; range, 4 months to 5.1 years). Curative resection could be performed on 46% of patients (69 of 150), noncurative resection on 12% (18 of 150), while 42% were found to be unresectable (63 of 150). Thirty-day surgical mortality and morbidity rates in patients with attempted resection were 2.7% and 13%, respectively. The curative resection group was observed to have an improved median survival (37.1 months) compared with the noncurative resection group (21.2 months) and the unresectable group (16.5 months) (P less than .01). Computed tomographic (CT) scan was a poor predictor for resectability, and age was not a contraindication to curative resection. Preoperative carcinoembryonic antigen (CEA) values were also a poor predictor for resectability. However, the median CEA value 61 to 180 days postsurgery was significantly higher in unresectable patients compared with median CEA levels in noncuratively and curatively resected groups (P less than .01). Our results imply that curative resection leads to an increase in median survival. Noncurative resection provides no benefit to asymptomatic patients, since unresectable and noncurative resection groups have similar life expectancies. Longer follow-up will be needed to demonstrate the ultimate impact of curative resection on survival.

Spiral Computerized Tomography in the Evaluation of Acute Flank Pain: A Replacement for Excretory Urography

PURPOSE We determined the value of noncontrast enhanced spiral computerized tomography (CT) in the evaluation of suspected renal colic. MATERIALS AND METHODS Thin section (5 mm.) noncontrast enhanced CT was used to evaluate 100 patients presenting to the emergency room with flank pain. The 55 patients with ureteral obstruction were followed at the urology outpatient clinic and by telephone interview, while 45 without ureteral obstruction were followed by telephone interview and chart review. Sensitivity, specificity, and positive and negative predictive values for CT were determined, with passage, retrieval or identification of a stone on a retrograde study considered the gold standard for diagnosis. RESULTS A total of 89 patients had adequate clinical followup to assess outcome accurately. Of 55 patients with ureteral obstruction on CT 11 underwent endoscopic stone removal, while 44 were treated conservatively with stone passage documented in 39. Of the 45 patients without ureteral stones identified 38 did not pass calculi and CT provided a definite diagnosis in 14. There was 1 false-negative study. The results yielded 98% sensitivity, 100% specificity, and 100% positive and 97% negative predictive values. CONCLUSIONS Noncontrast enhanced spiral CT was accurate and reliable in detecting obstructing ureteral calculi in patients with flank pain.

Magnetic Resonance Image-guided Salvage Brachytherapy After Radiation in Select Men Who Initially Presented With Favorable-risk Prostate Cancer A Prospective Phase 2 Study

The authors prospectively evaluated the late gastrointestinal (GI) and genitourinary (GU) toxicity and prostate‐specific antigen (PSA) control of magnetic resonance imaging (MRI)‐guided brachytherapy used as salvage for radiation therapy (RT) failure.

Neoadjuvant Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin With Pegfilgrastim Support in Muscle-Invasive Urothelial Cancer: Pathologic, Radiologic, and Biomarker Correlates

PURPOSE In advanced urothelial cancer, treatment with dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) results in a high response rate, less toxicity, and few dosing delays. We explored the efficacy and safety of neoadjuvant ddMVAC with pegfilgrastim support in muscle-invasive urothelial cancer (MIUC). PATIENTS AND METHODS Patients with cT2-cT4, N0-1, M0 MIUC were enrolled. Four cycles of ddMVAC were administered, followed by radical cystectomy. The primary end point was pathologic response (PaR) defined by pathologic downstaging to ≤ pT1N0M0. The study used Simons optimal two-stage design to evaluate null and alternative hypotheses of PaR rate of 35% versus 55%. Secondary end points included toxicity, disease-free survival (DFS), radiologic response (RaR), and biomarker correlates, including ERCC1. RESULTS Between December 2008 and April 2012, 39 patients (cT2N0, 33%; cT3N0, 18%; cT4N0, 3%; cT2-4N1, 43%; unspecified, 3%) were enrolled. Median follow-up was 2 years. Overall, 49% (80% CI, 38 to 61) achieved PaR of ≤ pT1N0M0, and we concluded this regimen was effective. High-grade (grade ≥ 3) toxicities were observed in 10% of patients, with no neutropenic fevers or treatment-related death. One-year DFS was 89% versus 67% for patients who achieved PaR compared with those who did not (hazard ratio [HR], 2.6; 95% CI, 0.8 to 8.1; P = .08) and 86% versus 62% for patients who achieved RaR compared with those who did not (HR, 4.1; 95% CI, 1.3 to 12.5; P = .009). We found no association between serum tumor markers or ERCC1 expression with response or survival. CONCLUSION In patients with MIUC, neoadjuvant ddMVAC was well tolerated and resulted in significant pathologic and radiologic downstaging.

The National Cancer Data Base report on patterns of care for testicular carcinoma, 1985-1996.

Previous Commission on Cancer data from the National Cancer Data Base (NCDB) have examined time trends in stage of disease, treatment patterns, and survival for selected cancers. In the current study data relating to patients diagnosed with testicular carcinoma in 1985, 1986, 1990, 1991, 1995, and 1996 are described.

COMBINATION OF SYMPTOM SCORE, FLOW RATE AND PROSTATE VOLUME FOR PREDICTING BLADDER OUTFLOW OBSTRUCTION IN MEN WITH LOWER URINARY TRACT SYMPTOMS

PURPOSE The severity of lower urinary tract symptoms associated with benign prostatic enlargement correlates poorly with bladder outlet obstruction. Since urodynamic studies are presumed to be relatively complex, invasive and not cost-effective, they are not routinely performed by physicians treating men with lower urinary tract symptoms. As a result, a large number of patients are treated for bladder outlet obstruction when in fact obstruction may not be present. Since other noninvasive methods have not been effective for predicting bladder outlet obstruction, we investigated whether a combination of prostate volume, uroflowmetry and the American Urological Association (AUA) symptom index would be reliable for predicting this condition. MATERIALS AND METHODS We prospectively evaluated 204 men with a mean age plus or minus standard deviation of 66.7 +/- 7.5 years who presented with lower urinary tract symptoms. Each patient completed an AUA symptom index questionnaire and underwent uroflowmetry, post-void residual urine volume measurement, pressure flow study and transrectal ultrasound of the prostate to estimate prostatic volume. We constructed receiver operating characteristics curves using various threshold values for maximum urine flow and prostate volume. Threshold values for maximum urine flow and prostate volume were used alone and combined with the AUA symptom index for predicting bladder outlet obstruction. We selected a cutoff value for maximum urine flow of 10 or less ml. per second and prostate volume of 40 gm. or greater, and used these values with an AUA symptom index of greater than 20 to predict bladder outlet obstruction in the group overall. RESULTS Differences in the mean symptom index score in men with and without bladder outlet obstruction were not statistically significant. There was no obstruction in 19%, 28.9% and 35% of those with severe, moderate and mild symptoms, respectively. The selected cutoff values of maximum urine flow, prostate volume and symptom score combined correctly predicted obstruction in all 39 patients. Therefore, our combination of cutoff values proved to be highly accurate for predicting bladder outlet obstruction. Sensitivity, specificity, and positive and negative predictive values were 26%, 100%, 100% and 32%, respectively. CONCLUSIONS Our study showed that combining the AUA symptom index, maximum urine flow and prostate volume reliably predicted bladder outlet obstruction in a small subset of patients only. Although bladder outlet obstruction was correctly predicted by our threshold values of AUA symptom index, maximum urine flow and prostate volume in only 39 men (26%) with obstruction, these patients represent a substantial group in any large urological practice treating male lower urinary tract symptoms.

Spiral CT in the evaluation of flank pain: overall accuracy and feature analysis.

PURPOSE Our goal was to assess test reliability and identify those features that have the strongest positive and negative predictive values in the diagnosis of renal colic using spiral CT. METHOD Fifty non-contrast-enhanced CT scans (5 mm slice thickness) obtained in patients presenting with flank pain were reviewed by three radiologists blinded to the final diagnoses. The sensitivity, specificity, and positive and negative predictive values for nine pertinent findings were determined as compared to clinical follow-up. RESULTS Twenty-nine cases had findings of ureteral obstruction. Findings with the strongest positive predictive values (> 0.90) were ureteral stone, hydronephrosis, hydroureter, periureteral stranding, and ureterovesical junction edema. Findings with the strongest negative predictive values (> 0.89) were absence of hydronephrosis and hydroureter. The areas under the receiver operating curves for Readers 1, 2, and 3 were 0.970 +/- 0.030, 0.942 +/- 0.036, and 0.982 +/- 0.020. CONCLUSION Absence of hydroureter and hydronephrosis on spiral CT images should prompt a search for a diagnosis other than an obstructing ureteral stone.

Morbidity of open retroperitoneal lymph node dissection for testicular cancer: contemporary perioperative data.

Study Type – Therapy (prospective cohort)
Level of Evidence 2b

Blood-Based Biomarkers of Aggressive Prostate Cancer

Purpose Prostate cancer is a bimodal disease with aggressive and indolent forms. Current prostate-specific-antigen testing and digital rectal examination screening provide ambiguous results leading to both under-and over-treatment. Accurate, consistent diagnosis is crucial to risk-stratify patients and facilitate clinical decision making as to treatment versus active surveillance. Diagnosis is currently achieved by needle biopsy, a painful procedure. Thus, there is a clinical need for a minimally-invasive test to determine prostate cancer aggressiveness. A blood sample to predict Gleason score, which is known to reflect aggressiveness of the cancer, could serve as such a test. Materials and Methods Blood mRNA was isolated from North American and Malaysian prostate cancer patients/controls. Microarray analysis was conducted utilizing the Affymetrix U133 plus 2·0 platform. Expression profiles from 255 patients/controls generated 85 candidate biomarkers. Following quantitative real-time PCR (qRT-PCR) analysis, ten disease-associated biomarkers remained for paired statistical analysis and normalization. Results Microarray analysis was conducted to identify 85 genes differentially expressed between aggressive prostate cancer (Gleason score ≥8) and controls. Expression of these genes was qRT-PCR verified. Statistical analysis yielded a final seven-gene panel evaluated as six gene-ratio duplexes. This molecular signature predicted as aggressive (ie, Gleason score ≥8) 55% of G6 samples, 49% of G7(3+4), 79% of G7(4+3) and 83% of G8-10, while rejecting 98% of controls. Conclusion In this study, we have developed a novel, blood-based biomarker panel which can be used as the basis of a simple blood test to identify men with aggressive prostate cancer and thereby reduce the overdiagnosis and overtreatment that currently results from diagnosis using PSA alone. We discuss possible clinical uses of the panel to identify men more likely to benefit from biopsy and immediate therapy versus those more suited to an “active surveillance” strategy.

Sucrase-isomaltase is an independent prognostic marker for colorectal carcinoma

PURPOSE: Expression of disaccharidase sucrase-isomaltase (SI) is significantly enhanced during neoplastic transformation of colonic epithelium. Our study was designed to determine whether expression of SI within primary tumors was significantly associated with survival in patients with colorectal carcinoma (CRC). METHODS: SI expression was analyzed by immunohistochemistry in paraffin sections from 182 Stage I to III CRC that had been resected for cure at the New England Deaconess Hospital between 1965 and 1977. Expression was scored as absent or present in 1 to 50 percent or more than 50 percent of tumor cells. Associations were explored among SI expression, other clinical or pathologic variables, and overall survival. The data set is mature, with 91 (56 percent) patients who had died of CRC at a median follow-up of 96 months. RESULTS: Fifty-five percent of primary CRC expressed SI. When the multivariate Cox analysis was performed, nodal status, T stage, primary site, grade, and SI expression were independent covariates. SI expression was not associated with the expression of other clinicopathologic variables but increased the risk of death from colorectal carcinoma by 1.83-fold. DISCUSSION: These results indicate that SI is a prognostic marker for CRC that is independent of stage-related variables in patients who have undergone potentially curative resections.