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Biomedical subjects

R H Riffenburgh

Publications and source records attributed to R H Riffenburgh.

At least 19 recordsLinked to original sources
PubMed2007

Lack of survival benefit of post-operative radiation therapy in prostate cancer patients with positive lymph nodes.

Randomized data from SWOG 8794 and EORTC 22911 confirm the benefit of post-operative radiation therapy (RT) for selected patients with pT3 prostate cancer (CaP) after radical prostatectomy (RP). However, data regarding the potential benefit of RT for patients post-RP with positive lymph node (+LN) involvement are limited. We analyzed the Surveillance Epidemiology End Results (SEER) registry for population-based data on efficacy of post-operative RT for +LN patients after RP. As LN data have only been captured by SEER since 1988, we analyzed data for 1988-1992, with specific attention to 10-year relative survival (defined as observed survival divided by the survival of a gender-, age- and race-matched population cohort without disease). Specifically analyzed were data for 1921 patients with nonmetastatic prostate cancer who underwent surgery alone, or surgery followed by RT, and who had +LNs documented. SEER does not code the interval between surgery and RT, so the ratio of patients receiving salvage versus adjuvant therapy is unknown. Using follow-up data through 2002, post-diagnosis survival was examined by number of +LNs. There was no significant relative survival benefit for +LN patients receiving post-operative RT (chi(2)P=0.270). These data do not support routine use of post-operative RT for patients with +LNs in the surgical specimen.

Combined Modality Therapy↗
PubMed2006

A simple and general change-point identifier.

In a not-necessarily-stationary time-series, a Moving F statistic can identify points of change in the nature of the series model (the estimate of the underlying data-generating process), in its parameters, in residual variability, or in any combination of these. In addition, it can uncover changes masked by a reduction in residual variability. Patterns in the forces giving rise to the data may often be perceived. To form the Moving F, a theory of the process or a regression method on a baseline sample estimates the series model and the residual mean square about it is calculated. This series model is extended past the baseline with residuals assumed to be normally distributed. The Moving F is calculated as the moving average of squared deviations about the series model in ratio to the baseline mean square. The Moving F crossing the critical F identifies a change in the series model, i.e. signals its presence and location. In our experience, this Moving F method is easier to use than other commonly employed change-point identifiers (CUSUM, EWMA, data-based bandwidth selection, MCMC) and has been found to work in several situations where some other identifiers fail. (MCMC is more general, but requires advanced statistical ability.) Examples given are monitored prostate specific antigen in a post-treatment prostate cancer patient and detection of Harold Shipman's medical murders. Moving F is 'simple and general' in the sense of both simultaneously; we have not found another relatively simple method to be as general.

Computer Simulation↗
PubMed2004

The 100-day PSA: usefulness as surrogate end point for biochemical disease-free survival after definitive radiotherapy of prostate cancer.

Overall and biochemical disease-free (bNED) survival data after definitive radiotherapy (RT) for prostate cancer (CaP) requires decades of patient follow-up. Surrogates involving dynamics of prostate-specific antigen (PSA) decline, PSA nadir and time thereto have been unrewarding. This study investigated the metric of the PSA value 100 days after RT (PSA(100)), analyzed with respect to 8-y bNED survival. A total of 214 patients with T1-3 CaP were treated with definitive RT (defined as dose >66 Gy) in our institution between 1/1/1988 and 12/31/2000. All were subject to continuous follow-up with routine PSA levels. Biochemical failure (77 patients) was defined by the ASTRO criteria (n=67) or by the date of first hormonal therapy for a rising PSA, which did not meet the ASTRO criteria (n=10). No patients were included if they received postoperative radiation, or if hormones were administered prior to bNED recurrence, if any. Patients were stratified by PSA(100) values </= or >4.0 ng/ml, and </= or <2.5 ng/ml. Median follow-up was 64.3 months: follow-up data were calculated as of time to last PSA, with data collection as of 12/31/02. Patients with PSA(100)</=4.0 ng/ml had 62% 8-y bNED survival, and those with PSA(100)>4.0 ng/ml had 20% 8-y bNED survival (P<0.001). Use of a PSA(100) cutoff of 2.5 ng/ml yielded no significant difference in 8-y bNED survival (P=0.229). Cox proportional analysis revealed that initial PSA (P=0.006), stage (P=0.001) and PSA(100)</=4.0 ng/ml (P=0.002) were significantly related to bNED survival, but that age (P=0.887), race (P=0.500), RT dose (P=0.669), Gleason sum (P=0.091), and PSA(100)</=2.5 ng/ml (P=0.128) were not. In conclusion, PSA(100) using a cutoff of 4 ng/ml is a valuable and reliable surrogate for bNED survival after definitive RT, requiring less follow-up than other metrics. Patients with less values will have only about a 1 in 3 chance of bNED failure at 8 y.

Aged↗
PubMed2003

Use of early PSA velocity to predict eventual abnormal PSA values in men at risk for prostate cancer.

The purpose of this study was to determine if early PSA velocity (EPSAV), drawn from PSA values within normal ranges, predicts the later occurrence of abnormally high PSA values or positive prostate biopsy early enough to be clinically beneficial. Early PSAV (ng/ml/y) calculated from two normal PSA readings was tested to predict later PSA exceeding 4 ng/ml (1551 evaluable patients) or 10 ng/ml (1905 evaluable patients) and positive prostate biopsy. The time from EPSAV to develop abnormal PSA was recorded.A post-EPSAV PSA>4 ng/ml was reached by 367 patients and >10 by 293. EPSAV was significantly different (P<0.001) between patients whose PSA did or did not reach the PSA cut-off point and also significantly predicted a positive biopsy result (P<0.001). EPSAV predicted abnormal PSA more than 1 y in advance in 68 and 52% of the PSA 4 and 10 ng/ml cut-off point groups, respectively. Early PSAV from normal PSA readings may allow early detection of men at risk for prostate cancer. This may help identify men for earlier prostate biopsy or for less frequent PSA monitoring.

Adult↗
PubMed2002

Initiation of salvage therapy for prostate cancer.

Physicians and patients have variable and individual levels of comfort regarding when to begin salvage therapy for rising prostate specific antigen (PSA) after definitive treatment of prostate cancer. The decision to start salvage therapy is a multifactorial process for which few rigorous data or guidelines exist. A questionnaire survey of urologists of the Department of Defense (DoD) Center for Prostate Disease Research (CPDR) was undertaken to obtain current perspectives on when to begin salvage therapy for biochemical failure after definitive therapy. Variables of age, grade, T-stage, nodal status, performance status, latency since prior therapy, PSA velocity, and ploidy were prioritized in four clinical situations; subsequent questions assessed consensus PSA cut-offs for beginning adjuvant therapy in 84 clinical scenarios. Consensus on PSA cut-off points was limited to postoperative radiotherapy (RT), where values of 1.0-1.5 were the mean cut-off points. CPDR urologists consider salvage prostatectomy post-RT only for patients <70-y-old with node negative, grade 2-7 disease and excellent performance status. Ploidy was not generally considered useful in any scenario. Many variables in addition to PSA level are involved in the decision of when to commence adjuvant therapy for initial biochemical failure. These are strikingly interdependent, and few clear absolutes are evident from this questionnaire. This is a point of necessary further research and continued discussion among physicians caring for these patients.

Adult↗
PubMed2001

Survival patterns of cancer patients.

BACKGROUND: Optimal means of modeling death rates of large populations with a specific disease have not been described in the literature. METHODS: Statistical modeling was used on archival data. RESULTS: In the authors' prior publications describing the survival of untreated cancer patients, data that were adequately fitted by an exponential curve were found to be much better fitted by an inverse Gompertz curve (R(2) = 99.7% for untreated breast carcinoma, 99.9% for untreated cervical carcinoma). However, when data from treated patients are examined, fits show that successive stages begin at successive positions on the inverse Gompertz curve. Breast carcinoma data showed that treatment begun at an early stage raised survival to a linear decline; at an intermediate stage led to a modified inverse Gompertz, the earlier the stage at which therapy was begun, the greater the survival rate; and at a late stage exhibited an exponential decline showing a negligible effect of late treatment. Confidence in this approach was enhanced by its applicability using published data from the National Cancer Database for breast, pancreatic, bone, and skin cancers. CONCLUSIONS: The use of data modeling allowed us to assess realistically the value of intervention in cancer populations and to optimize staging schemas. It strongly reinforced the concept that early detection provides a far greater impact on a population's subsequent survival than therapy of advanced disease.

Breast Neoplasms↗
PubMed2001

Relationship between obesity and race in predicting adverse pathologic variables in patients undergoing radical prostatectomy.

OBJECTIVES: To determine whether obesity is associated with more advanced prostate cancer (PCa) in radical prostatectomy patients and to explore the ethnic variability in body mass index (BMI) as a potential explanation for racial differences in PCa risk. METHODS: A multi-institutional retrospective analysis of the clinical and pathologic parameters was performed on data from 860 patients with PCa undergoing radical prostatectomy between 1992 and 1998. Patient height and weight was used to calculate the BMI, which categorized patients into obese (BMI 30 kg/m(2) or greater), overweight (BMI 25 to 30 kg/m(2)), and normal (BMI 25 kg/m(2) or less) groups. Age, serum prostate-specific antigen level, pathologic stage, and Gleason score for each group were compared. The distribution of the BMI in each of four ethnic groups was also determined. RESULTS: Of 860 patients, 171 (20%) were obese, 425 (49%) overweight, and 264 (31%) normal. The obese patients presented at a younger mean age (62 years, P = 0.001), had higher mean Gleason scores (6.7, P = 0.002), had a higher likelihood of Gleason score 7 or greater cancer (71%, P = 0.003), and had a lower chance of organ-confined cancer (46%, P = 0.050). The BMI was highest in blacks, followed by whites and Asians, and blacks had significantly higher grade cancers (P = 0.045). In multiple logistic regression analysis of the BMI and race, only BMI remained an independent predictor of Gleason grade. CONCLUSIONS: Obese patients with PCa present for radical prostatectomy at a younger age with higher grade and more pathologically advanced cancers. Blacks have higher grade cancers than other ethnic groups and, at the same time, have significantly higher BMIs. These findings suggest that obesity may in part account for the racial variability in PCa risk.

Age Factors↗
PubMed2001

20-year outcome of patients with T1-3N0 surgically staged prostate cancer treated with external beam radiation therapy.

PURPOSE: Patients with surgically staged localized prostate cancer treated with external beam radiation therapy were retrospectively analyzed for 15 and 20-year overall and cause specific survival. The need for additional therapy was also evaluated. MATERIALS AND METHODS: We analyzed 145 patients who received external beam radiotherapy after negative staging pelvic lymphadenectomy. Followup data were available for 129 patients. Overall and cause specific survival was calculated with the Kaplan-Meier method. RESULTS: Median followup was 14.9 years. Actuarial overall survival at 15 and 20 years was 45.9% and 24.6%, respectively. Cause specific survival at 15 and 20 years was 64.5% and 37.7% for having all patients dying of unknown causes censored, and 54.4% and 30.1% for those dying of unknown causes categorized as having prostate cancer, respectively. Of the patients who survived 47% were on hormonal therapy. CONCLUSIONS: Longer followup after external beam radiation therapy continues to demonstrate a decrease in cause specific survival. Many patients ultimately require hormonal therapy.

Aged↗
PubMed2001

Efficacy of digital rectal examination after radiotherapy for prostate cancer.

PURPOSE: Digital rectal examination is widely performed for following patients with localized prostate cancer after definitive therapy. This examination has marginal efficacy for detecting initial prostate cancer and postoperative recurrence. To determine the efficacy of digital rectal examination in terms of new information provided after radiotherapy we analyzed the results of digital rectal examination in the followup of patients with prostate cancer after radiotherapy. MATERIALS AND METHODS: We performed a nonrandomized study in 235 consecutive patients with prostate cancer followed at a large tertiary care military hospital between January 1, 1995 and December 31, 1999. All patients had been treated with prostate radiotherapy and had no evidence of metastatic disease at the first visit within that interval. Digital rectal examination was done at followup and the main outcome measure was new information provided by that examination. RESULTS: A total of 1,544 digital rectal examinations were performed in 1,627 visits. New information was provided by digital rectal examination in only 30% of 286 abnormal examinations, of which more than three-quarters were related to bleeding and would otherwise have been noted on routine examination by the primary care provider. All 8 persistent recurrent prostate nodules were noted in the context of increasing prostate specific antigen. CONCLUSIONS: Routine digital rectal examination in patients with prostate cancer after radiotherapy may be omitted from followup protocols.

Combined Modality Therapy↗
PubMed2000

Impact of socioeconomic status and race on clinical parameters of patients undergoing radical prostatectomy in an equal access health care system.

OBJECTIVES: To analyze the relationships among socioeconomic status (SES), race, and the clinical parameters of patients undergoing radical prostatectomy (RP) in an equal access health care system. METHODS: The Department of Defense Center for Prostate Disease Research longitudinal prostate cancer database from multiple military institutions was used to analyze the clinical, pathologic, and outcome data of 1058 patients with localized (Stage T2c or lower) prostate cancer and a preoperative prostate-specific antigen (PSA) level of 20 ng/mL or less who underwent RP between January 1987 and December 1997. Military rank (officer versus enlisted) was used as a surrogate measure of SES. RESULTS: The percentage of patients with pathologic Gleason grade 7 or greater prostate cancer was higher in enlisted (45%) than in officer (37%) patients (P = 0. 021). However, no difference was found between these groups with respect to pathologic stage or biochemical recurrence rates. African Americans presented at a younger age (P = 0.003), with a higher pretreatment PSA level (P = 0.001), and demonstrated higher biochemical recurrence rates than other ethnic groups (P = 0.037). The Cox proportional hazards analysis showed that a lower SES (P = 0.010) but not African American race (P = 0.696) was an independent predictor of a higher grade (Gleason grade 7 or higher) cancer. However, biochemical progression was more common in African American men (P = 0.035) and was not related to SES (P = 0.883). CONCLUSIONS: In an equal access health care system, patients of lower SES presented with higher grade prostate cancer at the time of RP. However, only African American race predicted biochemical progression after RP.

Age Factors↗
PubMed2000

Survival of patients with untreated breast cancer.

Knowing the clinical prognosis of untreated breast cancer is useful in dealing with patients with neglected disease or in environments with poorly developed healthcare systems. This study analyzes historical survival data in two sets of untreated patients: (1) 250 patients followed until death (up to 12 years) for which autopsy results are available and (2) an amalgam of 1,022 patients from several papers. Data from nine published papers underwent actuarial analysis. Median survival time of the 250 patients followed to death was 2.7 years. Actuarial 5- and 10-year survival rates for these patients with untreated breast cancer was 18.4% and 3.6%, respectively. For the amalgamated 1,022 patients, median survival time was 2.3 years. Actuarial 5- and (partially fitted) 10-year survival rates for these patients with untreated breast cancer was 19.8% and 3.7%, respectively. Historical data of untreated breast cancer patients reveal a potential for long survival in some cases. The spectrum of clinical aggressiveness of breast cancer varies between virulence and chronic disease.

Actuarial Analysis↗
PubMed2000

Extensive repeat transrectal ultrasound guided prostate biopsy in patients with previous benign sextant biopsies.

PURPOSE: Standard sextant prostate biopsy may underestimate cancer in men in whom clinical findings are suspicious for localized prostate cancer. We describe our experience with extensive transrectal ultrasound guided prostate biopsy in men in whom previous sextant biopsy was negative. MATERIALS AND METHODS: Between November 1997 and March 1999, 57 men 47 to 72 years old (mean age 61.4) underwent extensive transrectal ultrasound guided biopsy of the prostate using intravenous sedation at our institution. An average of 22.5 cores (range 15 to 31) were obtained depending on prostate size. Biopsies were obtained from each of 6 sagittal regions, including samples from the far lateral and mid transitional zones. Each patient had undergone at least 1 previous benign transrectal ultrasound guided sextant biopsy (mean 2.1, range 1 to 4). Indications for repeat biopsy were persistently elevated prostate specific antigen (PSA) in 89% of the cases, increased PSA velocity in 63%, suspicious free-to-total PSA in 39% and a previous suspicious biopsy finding in 32%. Clinical factors (PSA, PSA velocity, free-to-total PSA and previous suspicious biopsy) were analyzed for the ability to predict positive biopsy, and tumor parameters were assessed pathologically in patients undergoing radical prostatectomy. RESULTS: Adenocarcinoma was identified in 17 of the 57 men (30%). Biopsy revealed a Gleason score of 6 to 8 (mean 6.4). In 7 of the 17 patients (41%) in whom cancer was identified only 1 biopsy core was positive. Of the 15 patients in whom previous sextant biopsy had demonstrated high grade prostatic intraepithelial neoplasia or atypical small acinar proliferation extensive biopsy revealed cancer in 7 (47%). Although serum PSA was higher and free-to-total PSA was lower in those with cancer, the only statistically significant predictor of positive biopsy was PSA velocity (p <0.001). Prostate cancer was noted in 64% of the men with PSA velocity 1 ng./ml. or greater. Of the 13 patients undergoing radical prostatectomy pathologically significant disease was identified in all but 1 (92%). Complications of extensive biopsy included urinary retention in 6 patients and limited rectal bleeding in 1. CONCLUSIONS: Extensive prostate biopsy identifies significant prostate cancer in many men in whom previous sextant biopsy was benign. This procedure should be considered when findings are suspicious for adenocarcinoma despite previously negative sextant biopsy.

Adenocarcinoma↗
PubMed1999

Development of open-scope subfascial perforating vein surgery: lessons learned from the first 67 cases.

Although perforating vein surgery in treatment and prevention of venous ulcers remains controversial, minimization of the procedure has allowed its reevaluation. We have chosen to develop the technique using a single port and an open scope using a variety of mostly nondisposable instrumentation. Since our first subfascial endoscopic perforator vein surgical (SEPS) procedure in July 1993, we have operated on 67 limbs in 62 patients (27 women, 35 men) ranging in age from 24 to 85 years. Using CEAP criteria, there were 16 limbs in class 4, 13 in class 5, and 38 in class 6. Preoperative investigations included duplex ultrasound in 35 cases, ascending phlebography in 29 cases, and selective use of physiologic testing with air plethysmography (APG) in 12 patients. A variety of initial explorations using different-diameter scopes has given way to single-port methodology for medial leg exploration. A mean of 3.08 perforators per patient was interrupted using electrocoagulation or metal clips and scissor division. This technique, as developed, allows same-day or short-stay (<24 hr) surgery. A vigorous program of thromboembolism prophylaxis was used in selected cases. From these 67 csaes we conclude that endoscopic perforating vein interruption provides a useful tool for the surgeon interested in treating severe chronic venous insufficiency. The open-scope, single-port technique accomplishes intervention objectives in a simplified manner. Although recurrent chronic venous insufficiency (CVI) is not eliminated, its postoperative treatment is markedly eased.

Adult↗
PubMed1997

Outcome for surgically staged localized prostate cancer treated with external beam radiation therapy.

PURPOSE: A retrospective analysis was performed on patients with surgically staged localized prostate cancer treated with external beam radiation therapy for 10-year overall, cause specific and disease-free survivals based on lack of clinical recurrence and 2 separate prostate specific antigen criteria for cure. MATERIALS AND METHODS: We analyzed 145 patients who received external beam radiation therapy after a negative staging pelvic lymphadenectomy for prostate cancer. Followup data were available for 129 patients (90%). Disease was stage A in 29 patients (22.5%), stage B in 64 (49.6%), stage B2/C in 2 (17%) and stage C in 14 (10.9%). Average potential followup from date of diagnosis was 11.5 years (minimum 7.2). Of the patients 87 potentially can be followed for longer than 10 years. Disease-free survival was based on a normal digital rectal examination, lack of symptoms suspicious for metastasis and application of 2 separate prostate specific antigen criteria of 4 ng./ml. or less (group 1), or 1.5 ng./ml. or less (group 2). Survival was analyzed with the Kaplan-Meier actuarial method. RESULTS: Actuarial overall survival at 10 and 15 years was 63.7 and 49.6, respectively, and cause specific survival was 84.2 and 80%, respectively. Disease-free survival was 54.5 and 32.4%, respectively, for group 1, and 42.3 and 9.6%, respectively, for group 2. CONCLUSIONS: The improved patient selection inherent in surgical staging before definitive external beam radiation therapy provides for improved overall and cause specific survival over that of patients without surgical staging. Biochemical disease-free survival also appears to be improved.

Aged↗
PubMed1997

Association of schistosomiasis with cervical cancer: detecting bias in clinical studies.

To investigate if Schistosoma haematobium infection increases the observed frequency of cervical cancer, data from literature were analysed in meta-analysis fashion. Results reveal that cervical cancer is statistically significantly less frequent in the presence of S. haematobium infection. A protective effect might be inferred; however, underlying bias in data collection and/or analysis is suspected. An approach to detecting bias is given, consisting of: (a) carefully stating and assessing the several components of the scientific method and; (b) identifying and contrasting the populations hypothesised and sampled. The approach is illustrated by searching for bias in the schistosomiasis-and-cancer reports. Sampling discrepancies were detected in patient geography, ages, and states of health, and suspected in disease prevalence sampled and disease prevalence reported. The conclusion is reached that effects of bias in the original studies preclude inference of a "protective" effect of S. haematobium infection against cervical cancer.

Africa↗
PubMed1996

Reverse gullibility and scientific evidence.

A 19th century image of the medical profession's attitude toward disease transmission is introduced through Ignaz Semmelweis' hypothesis: Infection can be caused by an external agent transmitted when physicians fail to sterilize their hands between patient examinations. Semmelweis' test of his hypothesis reduced the obstetrical death rate from 18% to almost 1%. However, he was degraded, defrocked, and driven to death by a profession whose emotions contradicted the evidence. Medical professionals like to believe they are not gullible, a trait defined as being easily duped. They rightly believe in their ability to avoid the error of accepting a result not supported by adequate evidence. They are not so free of the complementary error: refusing to accept a result that is supported by adequate evidence, which might be thought of as reverse gullibility. It is just as bad a logical error and just as serious a denial of the best medical care for our patients. Clearly Semmelweis, and later Louis Pasteur and others who were disbelieved, were correct. The profession was duped by its emotional adherence to current practice. To be truly professional, let us believe our evidence rather than our biases and not suffer from reverse gullibility.

Attitude of Health Personnel↗