Analysis of heterogeneity in human tumors: a unique role for flow and image cytometry?
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Flow Cytometry↗
Biomedical subjects
R C Flanigan
Publications and source records attributed to R C Flanigan.
Renal cell carcinoma: considerations for nephron-sparing surgery.
OBJECTIVES: The performance of nephron-sparing surgery in patients with a normally functioning contralateral kidney is controversial. To explore the risk factors that may contribute to the success or failure of nephron-sparing surgery, we examined the radiology and pathology reports of 278 patients who underwent radical nephrectomy for the treatment of clinically localized renal cell carcinoma. METHODS: We collated patient data from the records of 278 patients with Stage III renal cell carcinoma entered into the Eastern Cooperative Oncology Group protocol EST 2886 and compared preoperative clinical staging with postoperative pathologic results. Patients were considered potential candidates for nephron-sparing surgery if their preoperative radiographic studies indicated that the carcinoma was a single polar lesion 5 cm or less in diameter. RESULTS: Of 278 radical nephrectomy specimens, 36 had primary lesions 5 cm or less in diameter. Preoperative radiographic studies showed 14 of 36 would not have been considered eligible for nephron-sparing surgery. Of the remaining 22 potential candidates, pathologic studies showed multifocal lesions in 11, renal vein disease in 4, and nodal disease in 2. Only 5 of 22 patients might have had specimen-confined disease (T3a lesion). CONCLUSIONS: Capsular-penetrating (T3a) renal cell carcinoma is not often appreciated preoperatively and is associated frequently with multifocal lesions, renal vein or nodal disease. Frozen section studies to rule out T3a disease at the time of nephron-sparing surgery may help determine which patients need radical surgery.
Carcinoma, Renal Cell↗
Renal arteriovenous malformations masquerading as renal cell carcinoma.
Renal arteriovenous malformations may have varied clinical and radiographic appearances. Often, it remains difficult to distinguish these lesions from renal cell carcinomas to tailor the most appropriate diagnostic evaluation and therapy. We have encountered 6 patients with renal arteriovenous malformations that masqueraded as renal cell carcinomas and describe their clinical presentation and management.
Adult↗
The current TNM-classification of bladder carcinoma--is it as good as we need it to be?
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Carcinoma, Transitional Cell↗
Derivation and application of upper limits for prostate specific antigen in men aged 50-74 years with no clinical evidence of prostatic carcinoma.
OBJECTIVE: To derive age-specific upper limits for prostate specific antigen (PSA) level in men 50-74 years of age with no clinical evidence of prostatic carcinoma, and to test the sensitivity and specificity for cancer detection of these upper limits. SUBJECTS AND METHODS: A total of 6166 men were recruited for a multicentre study of prostate cancer detection and underwent a serum PSA determination and digital rectal examination (DRE). Men considered to be clinically free of prostatic carcinoma were those with a normal DRE and a PSA level < or = 4.0 ng/mL, and men with an abnormality in either parameter who underwent ultrasonography-guided prostate biopsy that revealed no evidence of carcinoma. By these criteria, 5469 men had no evidence of prostatic carcinoma. Dividing the population into 5-year age increments, three statistical methods were assessed to derive upper limits for serum PSA level by age; the mean +2 SD, the 99th percentile, and a 97.5% prediction interval based on linear regression. RESULTS: Newly-derived upper limits calculated by each method in the 50-54 and the 70-74 age group were 3.9 ng/mL and 7.6 ng/mL (mean +2 SD), 5.2 ng/mL and 14.0 ng/mL (99th percentile), and 4.7 ng/mL and 8.2 ng/mL (97.5% prediction interval). The sensitivity of the newly-derived upper limits was tested using receiver operating characteristic curves derived from men with no suspicious findings on DRE and a serum PSA concentration > 4.0 ng/mL. Although the specificity of the test increased with increasing PSA upper limits, no upper limits derived from these three methods yielded adequate sensitivity to detect cancer; sensitivities by age range were from 53 to 94%, using mean +2 SD, from 25 to 50% with the 99th percentile, and from 47 to 64% with the 97.5% prediction interval. CONCLUSION: We do not recommend age-referenced adjustments in upper limits for serum PSA concentration, but recommend that an upper limit of 4.0 ng/mL be used in all men 50-74 years of age.
Aged↗
Evaluation of low dose continuous infusion 5-fluorouracil in patients with advanced and recurrent renal cell carcinoma. A Southwest Oncology Group Study.
BACKGROUND: The response rate of metastatic renal cell cancer to cytotoxic therapy over the last 10 years has been 5.6%. Low dose continuous 5-fluorouracil (5-FU) has demonstrated efficacy in other cytotoxic refractory tumors, such as pancreas, colorectal, and recurrent breast. The Southwest Oncology Group undertook a Phase II trial of low dose, continuous 5-FU in metastatic renal cell cancer. METHODS: Sixty-one patients were entered in the study to receive 300 mg 5-FU/m2/day for 7 days via a central venous catheter and external programmable pump. The pump was refilled every 7 days. Pyridoxine (50 mg, orally) was administered prophylactically three times a day. RESULTS: A response of 5.2% (one complete response [CR] and two partial responses [PRs]) was achieved. The overall survival was 12 months. The duration of the CR is more than 30 months. Both PRs lasted 6 months. No survival advantage was noted with either prior nephrectomy or biologic therapy. The majority of toxicities were Grade 2: anemia, anorexia, diarrhea, nausea/vomiting, and stomatitis. No toxic deaths occurred. CONCLUSION: Low dose, continuous 5-FU demonstrated minimal activity in metastatic renal cancer.
Carcinoma, Renal Cell↗
Phase II evaluation of merbarone in renal cell carcinoma.
The Southwest Oncology Group (SWOG) studied the response rate and toxicity of merbarone (1,000 mg/m2 IV continuous infusion days 1-5, q 21 days) in patients with advanced metastatic renal cell carcinoma. Among 36 eligible patients, there was one partial response for a response rate of 3% (95% C.I. 0.1-15%). There were no mixed responses. There were no treatment related deaths or adverse drug reactions. Significant anemia, diarrhea, and hypercalcemia were observed. Mild to moderate degrees of malaise/fatigue/lethargy, dizziness/vertigo, hyperglycemia, creatinine increase, nausea, vomiting, weight loss, pedal edema, dyspnea, and granulocytopenia were noted. Merbarone does not have significant activity as a single agent in advanced renal cell carcinoma.
Antineoplastic Agents↗
Parapubic hernia following radical retropubic prostatectomy.
We report a parapubic hernia in a 54-year-old patient following radical retropubic prostatectomy. This complication can occur when the musculotendinous insertions of the rectus abdominis muscle are divided from the pubis. Bowel contents herniate over the pubic crest and can be misdiagnosed as an incisional or inguinal hernia. Successful repair depends on closure of the entire defect. Elective repair necessitates the use of prosthetic mesh.
Hernia, Ventral↗
Directed and random biopsies of the prostate: indications based on combined results of transrectal sonography and prostate-specific antigen density determinations.
OBJECTIVE: We studied the usefulness of transrectal sonography, prostate-specific antigen levels, and prostate-specific antigen density as indications for directed and random biopsies of the prostate in patients with possible prostatic cancer. MATERIALS AND METHODS: A total of 141 patients with increased levels of prostate-specific antigen or abnormal findings on digital rectal examination had transrectal sonography of the prostate and determination of prostate-specific antigen density. Through sonographic visualization, all patients had biopsies of possible cancerous lesions and random biopsies of regions of the prostate that appeared normal. Histologic results were correlated with sonographic findings and determinations of prostate-specific antigen levels and prostate-specific antigen density. RESULTS: Adenocarcinoma was detected in 40 (28%) of the 141 patients. Transrectal sonography showed an abnormality that was determined by directed biopsy to be a carcinoma in 27 (68%) of the 40 patients. Transrectal sonography showed no carcinoma in 13 patients (32%) for whom random biopsy revealed a tumor. The sensitivity of sonography was 68%, and the specificity was 49%. The combination of sonographic findings suggestive of cancer and increased prostate-specific antigen density had a sensitivity of 75% and a specificity of 75%; we calculated a sensitivity of 72% and a specificity of 56% for the combination of sonographic findings suggestive of tumor and increased levels of prostate-specific antigen. Thirty-nine (97%) of 40 patients with cancer had either sonographic findings suggestive of tumor or increased prostate-specific antigen density, and one (3%) had no evidence of tumor on sonography and a normal prostate-specific antigen density. CONCLUSION: Directed and random sonographic biopsies of the prostate are indicated in patients with sonographic findings suggestive of tumor and increased prostate-specific antigen density and in patients with abnormal sonographic findings and normal prostate-specific antigen density. Random biopsies are indicated in patients with normal sonographic findings and increased prostate-specific antigen density. In our series, random biopsies were not indicated in 25 of 26 patients with normal sonographic findings and normal prostate-specific antigen density. Further research on the need for random biopsies when there are no sonographic abnormalities and when prostate-specific antigen densities are not elevated is warranted.
Adenocarcinoma↗
Radical prostatectomy: transrectal sonographic evaluation to assess for local recurrence.
PURPOSE: To determine sonographic features associated with locally recurrent or residual tumor. MATERIALS AND METHODS: Twenty-three transcretal ultrasound (TRUS) studies were performed in 21 patients with suspected recurrent prostatic carcinoma after prostatectomy. The original prospective TRUS reports were reviewed, followed by blinded review, and the findings were compared with biopsy results. RESULTS: A discrete perianastomotic mass was identified prospectively in eight (73%) of 11 patients with positive biopsy results and in two (17%) of 12 with negative results; no mass was identified in the remaining patients. At preliminary retrospective review, the echogenic retroanastomotic fat plane was not intact in 10 (91%) of 11 patients with positive biopsy results and in two (17%) of 12 with negative results; it was intact in the remaining patients. CONCLUSION: Sonographic visualization of a mass in the prostate bed or loss of integrity of the retroanastomotic fat plane is strongly correlated with finding recurrent or residual tumor in this location. TRUS in evaluation of the source of postoperative evaluation of prostate-specific antigen levels warrants further investigation.
Aged↗
Female urethral diverticular with clear cell adenocarcinoma.
Clear cell adenocarcinoma in a urethral diverticulum in the female is a very rare and unusual tumor. We recently treated two patients with this tumor. Their presentation, histologic evaluation, and management are reviewed in light of the limited experience in the literature.
Adenocarcinoma↗
Oxidative tryptophan metabolism in renal allograft recipients: increased kynurenine synthesis is associated with inflammation and OKT3 therapy.
Serum concentrations of tryptophan (TRP) and kynurenine (KYN) were determined in renal allograft recipients (RAR) as an index of interferon-gamma-induced, indoleamine-dioxygenase-catalysed TRP degradation. Serum TRP and KYN in RAR during periods of stable graft function were typically within the normal range, however, the median values for serum KYN demonstrated significant increases 5-7 days prior to biopsy-confirmed acute rejection (1.6-fold, P less than 0.01) and on the day of biopsy (1.7-fold, P less than 0.001). Serum KYN was also markedly elevated in patients who contracted viral or Gram-negative bacterial infections in the absence of graft rejection. Serum KYN was not correlated with serum creatinine in RAR nor were serum TRP or KYN affected by antirejection therapy with high dose steroids. Retrospective analysis of intra-patient changes in serum KYN demonstrated that KYN monitoring was a useful adjunct to serum creatinine in the early detection of first acute rejection episodes. The first course of OKT3 therapy was associated with low serum TRP and significant increases in serum KYN (two- to three-fold) following the first three doses. The time course of these abnormalities corresponded to that over which many of the side effects of the OKT3 'first dose reaction' have been reported to occur. Significant changes in serum KYN were not observed in patients receiving repeat courses of OKT3 therapy. Significant decreases in serum TRP and significant increases in serum KYN were both prevalent and frequent in RAR during the first two postoperative months.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Phase 1 trial of oral bropirimine in superficial bladder cancer.
A total of 34 patients with measurable superficial transitional cell cancer of the bladder entered into a phase 1, nonrandomized, noncomparative trial to assess the toxicity of the oral interferon inducer bropirimine. Of the patients 26 were also evaluable for response. The toxicity of bropirimine was minimal. At the 3-month evaluation 6 patients had experienced complete regression of tumor and had negative cytology studies, and 2 had partial responses. The majority of complete responses were in patients with carcinoma in situ only, with most responses seen at higher dose levels. One patient with papillary tumor and carcinoma in situ had a complete response. Some early responses appear to be durable. Most importantly, a high rate of complete response was noted at higher dose levels among patients who had failed prior therapy with bacillus Calmette-Guerin. Further clinical trials of bropirimine in bladder cancer appear warranted.
Administration, Oral↗
Superficial bladder disease: case studies and therapeutic advances.
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Administration, Intravesical↗
Analysis of iodine-125 interstitial therapy in the treatment of localized carcinoma of the prostate.
Definitive treatment of localized carcinoma of the prostate has included radical surgery, external beam radiation therapy, and interstitial radiation therapy. The interstitial agent most commonly used is Iodine-125. Forty-eight patients were treated with interstitial radiation therapy using Iodine-125 implants with a median follow-up of 55 months. Forty-three percent of the evaluable patients had progressive disease with approximately 50% progressing at 5 years by Kaplan-Meier analysis. Overall actuarial survival in the group was 80% at 5 years. This and several other studies suggest that control of prostate cancer with Iodine-125 seeds may be suboptimal as compared with other treatment modalities, especially the radical retropubic prostatectomy. Analysis of treatment parameters is presented along with a discussion of the current status and future prospects for treatment of localized carcinoma of the prostate with interstitial radiation therapy.
Actuarial Analysis↗
Free amino acids during chronic cyclosporine A toxicity in intact and partially nephrectomized rats.
The effects of 40 days of treatment with Cyclosporine A (CSA) on plasma and urine free amino acids were investigated in sham-operated (C) and partially nephrectomized (Pnx) female Fischer 344 rats. High Dose CSA (30 mg/kg/day ip) was associated with reduced weight gain, increased plasma urea nitrogen, and hypoproteinemia in C and Pnx animals. These animals also demonstrated increased plasma levels of alanine, markedly reduced levels of tryptophan, and an increase in urinary excretion of methylhistidines. C but not Pnx animals also showed a significant increase in plasma serine and a decrease in plasma taurine. CSA treatment of group C resulted in a progressive aminoaciduria involving substrates of the neutral and acidic renal amino acid transport systems; however, the renal excretion of taurine and beta-alanine by these animals was markedly reduced as compared to vehicle treated controls. High dose CSA exacerbated aminoaciduria in Pnx animals, but in this group, the excretion of beta amino acids was also increased. Our findings demonstrate that chronic CSA toxicity in rodents with normal renal function is characterized by increased muscle protein catabolism, significant reductions in plasma tryptophan, and an apparent decrease in whole body taurine pools. With the exception of the taurine abnormalities. CSA treatment had similar effects on Pnx animals; however, in this group, CSA-induced pathological changes were superimposed on the changes due to renal insufficiency per se. CSA toxicity as identified by the parameters investigated in this study was no more severe in Pnx animals with moderate chronic renal insufficiency than in controls with intact renal function.
Alanine↗