Paul Kolm

Comparative quality-of-life analysis after radical prostatectomy or external beam radiation for localized prostate cancer

OBJECTIVES To determine and compare quality-of-life (QOL) evaluations from patients who received external beam radiation therapy or radical prostatectomy for the treatment of localized prostate cancer, and to compare differences in QOL assessments for urinary and sexual function after radical prostatectomy as reported by patient and physician. METHODS Two hundred three patients treated by radical prostatectomy and 257 patients treated by external beam irradiation, all beyond 12-month follow-up after therapy, responded to a QOL questionnaire. The difference in responses with regard to bladder, bowel, and sexual function, overall satisfaction with treatment, and choice of the same treatment were assessed. Satisfaction with and choice of the same treatment were also specifically assessed according to bowel and bladder function and current disease status. The medical records of patients treated by radical prostatectomy were reviewed by an independent data manager to record the physicians assessment of continence and sexual function for comparison with that patients assessment as noted in the questionnaire. RESULTS Problems with urinary continence were more frequent among patients treated by radical prostatectomy; problems with gastrointestinal function were more frequent after irradiation. Sexual dysfunction was similar in both groups, although surgical patients experienced a greater impact on sexual relationships. The physician estimates of urinary continence were more favorable than the patient-reported outcomes. However, the physician estimate of sexual function closely approximated that of the patient. Preservation of sexual function among patients who underwent nerve-sparing surgery was disappointingly low. Only for the response to the question dealing with difficulty in achieving an erection was there a statistically significant benefit for patients receiving nerve-sparing versus non-nerve-sparing procedures. Patient satisfaction with and choice of the same treatment varied according to function and current disease status. Patients who had incontinence or bowel dysfunction or had evidence of recurrent disease were statistically less likely to choose the same treatment again when compared with functional and disease-free counterparts. Because irradiated patients were on average 6 years older than surgical patients, responses were adjusted for age; adjustment for age did not alter results. CONCLUSIONS QOL is determined by the treatment received, by the assessment source, and by the patients function and disease status at the time of assessment. Prospective and longitudinal studies will more accurately quantify immediate and chronic alterations in QOL. Uniformity of evaluation through consolidation of QOL instruments will permit more accurate cross-series and cross-treatment comparisons.

Defining the role of laparoscopic-assisted sigmoid colectomy for diverticulitis

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of laparoscopic-assisted sigmoid colectomy for the treatment of diverticulitis. METHODS: The Norfolk Surgical Group Laparoscopic Surgery Registry identified all patients undergoing laparoscopic colon and rectal surgery. Retrospective chart review was performed for all patients undergoing elective sigmoid resection for a final diagnosis of diverticulitis and minimum follow-up of 12 months. Demographic data, indications for surgery, operative data, conversion rate, reason for conversion, complications, postoperative course (days to flatus and regular diet), and length of stay were identified. A telephone survey determined the incidence of recurrent diverticulitis. Statistical analysis was performed to evaluate the frequency of conversion over time, to determine risk factors for conversion, and to compare the laparoscopic-assisted and conversion groups with regard to postoperative days to flatus, regular diet, and discharge. RESULTS: From June 1992 to September 1997, elective laparoscopic-assisted sigmoid colectomy was attempted in 69 patients. Uncomplicated recurrent diverticulitis was the most common indication for surgery, occurring in 51 of 69 patients (75 percent). No deaths occurred. Complications were identified in seven patients (10.1 percent) including one wound infection and one incarcerated port-site hernia with small bowel obstruction. There were no anastomotic leaks or major septic complications. Conversion to laparotomy occurred in 18 of 69 patients (26 percent). Uncomplicated, recurrent diverticulitis was associated with conversion in 7 of 51 patients (14 percent), whereas complicated diverticulitis required conversion in 11 of 18 patients (61 percent). Logistic regression identified fistula and abscess as predictors of conversion (P=0.0009). Comparison of the laparoscopic-assisted sigmoid colectomy group with the conversion group revealed that postoperative days to regular diet were 3.5 and 5.2 (P=0.0004), respectively, and lengths of stay were 4.2 and 6.4 days (P<0.0001), respectively. No difference was noted with regard to operative time or postoperative complications. Median follow-up was 48 (range, 13–76) months, and a single recurrence of diverticulitis has been identified. CONCLUSIONS: Laparoscopic-assisted sigmoid colectomy for diverticulitis can be safely performed. Conversion appears to be associated with complicated diverticulitis (fistula or abscess), which may be better approached by laparotomy. Short-term follow-up indicates that recurrence is rare and suggests that laparoscopic-assisted sigmoid colectomy achieves adequate resection. Laparoscopic-assisted sigmoid colectomy offers benefits of decreased ileus and length of stay and may represent the procedure of choice for elective resection for uncomplicated sigmoid diverticulitis.

Prostate-specific antigen to determine progression-free survival after radiation therapy for localized carcinoma of prostate

Prostate-specific antigen (PSA) levels after radiation therapy will more precisely and objectively identify the presence of persistent prostate carcinoma. We determined the impact of PSA marker levels on progression-free status for 123 patients treated by interstitial implantation (I-125) and 311 patients treated by external beam therapy (XRT) who have been followed for a median of 109 and 51 months, respectively. Actuarial progression-free survival curves were calculated, using standard clinical criteria, and then recalculated, using PSA marker criteria. Sera obtained twelve months or more after the initiation of XRT and twenty-four months or more after the date of I-125 were used for determination of PSA levels. Using normal PSA level (by Hybritech assay < or = 4.0 ng/mL) as the criterion for progression-free status for patients treated by XRT, 35 percent of patients with Stage A2, 20 percent of patients with Stage B1 or B2, and 10 percent of patients with Stage C tumor were progression-free at ten years. The progression-free survival by clinical criteria for Stage A2 and 65 percent, B1 was 40 percent, B2 was 35 percent, and C was 25 percent. Using undetectable PSA level (< or = 0.5 ng/mL) as the criterion, less than 10 percent of patients were progression-free at ten years, regardless of stage, grade; and treatment modality. This information should not be interpreted as indicating that radiation is ineffective therapy for prostate cancer, since clinical control of the disease among men in their eighth decade is a more practical goal than marker control. However, PSA monitoring after radiation therapy and after any local therapy for prostate cancer will provide more precise information on the success of that therapy in ablating disease.

Epidermal growth factor receptor: An independent predictor of survival in astrocytic tumors given definitive irradiation

PURPOSE To determine whether the expression of epidermal growth factor receptor (EGFR) protein was predictive of patient survival independently of other prognostic factors in astrocytic tumors. METHODS AND MATERIALS Epidermal growth factor receptor protein expression was investigated immunohistochemically in formalin-fixed, paraffin-embedded surgical specimens of 55 glioblastoma multiforme, 14 anaplastic astrocytoma, and 2 astrocytomas given definitive irradiation. We evaluated the relationship of EGFR protein expression and tumor grade, histologic features, age at diagnosis, sex, patient survival, and recurrence-free survival. RESULTS The percentage of tumor cells which were EGFR positive related to reduced survival by Cox regression analysis in both univariate (p = 0.0424) and multivariate analysis (p = 0.0016). Epidermal growth factor receptor positivity was the only 1 of 11 clinical and histological variables associated with decreased recurrence-free survival by either univariate (p = 0.0353) or multivariate (p=0.0182) analysis. Epidermal growth factor receptor protein expression was not related to patient age, sex, or histologic features. CONCLUSION Epidermal growth factor receptor positivity was a significant and independent prognostic indicator for overall survival and recurrence-free survival for irradiated patients with astrocytic gliomas.

Perifollicular blood flow Doppler indices, but not follicular pO2, pCO2, or pH, predict oocyte developmental competence in in vitro fertilization

OBJECTIVE To assess the relationships among perifollicular blood flow; follicular fluid pO2, pCO2, and pH; oocyte developmental capacity; preimplantation embryo quality. DESIGN Prospective study. SETTING Academic, tertiary care institution. PATIENT(S) Unselected, gonadotropin-stimulated IVF cycles. INTERVENTION(S) Color, pulsed Doppler analysis of perifollicular blood flow, and follicular pO2, pCO2, and pH determinations of randomly designated, mapped ovarian follicles. MAIN OUTCOME MEASURE(S) Fertilization and day 3 embryo cleavage and morphology. RESULT(S) Perifollicular vascularity indices were significantly and negatively correlated with day 3 embryo cleavage. Pulsatility index and S-D ratio also were significantly and negatively correlated with follicular pO2. The same correlation was found between resistance index and the fertilization rate of preovulatory oocytes. No relationship existed between follicular metabolic analysis and fertilization or embryo quality. The resistance index had a sensitivity of 0.57 and a specificity of 0.71 for the prediction of advanced embryo cleavage status. CONCLUSION(S) Results confirm and extend previous reports demonstrating that color, pulsed Doppler ultrasound analysis of individual preovulatory follicles during IVF therapy may provide an indirect index of the developmental competence of the corresponding oocyte. Although these methods may provide means to select embryos for transfer with the highest implantation potential, the moderate predictive power showed so far may limit their clinical applicability.

Management and prognosis of adenocarcinoma of the appendix

PURPOSE: Adenocarcinoma of the appendix is a rare neoplasm, and controversies persist regarding management. The purpose of this study was to identify prognostic factors and define management strategies for patients with adenocarcinoma of the appendix. METHODS: A retrospective case series was conducted at three medical school teaching hospitals over a 20-year period from 1972 to 1992. Overall survival was determined by the actuarial life table method. Comparisons of prognostic factors were made using exact nonparametric log-rank tests. RESULTS: Thirteen patients were diagnosed during the study period. Median age was 62 years. There were five males and eight females. The disease swas not suspected in any patient preoperatively. Seventyseven percent of patients had metastatic disease at presentation. Second primary malignancies were found in 15 percent of patients. Thirty-eight percent of female patients had synchronous ovarian lesions. Median survival was 22 months, with an estimated five-year survival of 43 percent (95 percent confidence interval, 22–84 percent). Patients with colonic histology had significantly worse survival than patients with mucinous histology (tP=0.0093). Patients with carcinomatosis had a significantly worse survival than noncarcinomatosis patients (tP=0.0078). Patients who underwent right hemicolectomy had a better prognosis for survival than appendectomy patients, but the difference was not statistically significant. CONCLUSIONS: Carcinoma of the appendix is very difficult to diagnose preoperatively, and most patients are not identified until disease is advanced. Good prognostic factors include mucinous histology and the absence of carcinomatosis. Right hemicolectomy appears to be a reasonable option, although its superiority to appendectomy alone has not been definitively proven. High frequency of ovarian metastases in women suggests a role for bilateral oophorectomy. In addition, a complete work-up of the patient for a synchronous malignancy, especially in the gastrointestinal tract, should be considered.

Embryo implantation in in vitro fertilization and intracytoplasmic sperm injection: impact of cleavage status, morphology grade, and number of embryos transferred

OBJECTIVE The aims of this study were to compare preimplantation embryo quality in intracytoplasmic sperm injection (ICSI) with standard IVF and to examine the impact of age and number and quality of embryos transferred on implantation and pregnancy. DESIGN Retrospective, controlled clinical study. SETTING Academic tertiary center. PATIENT(S) We examined 211 consecutive couples undergoing ICSI who were matched with 211 couples undergoing IVF therapy during the same time frame. INTERVENTION(S) In vitro embryo culture. MAIN OUTCOME MEASURE(S) Day 3 embryo quality as judged by the number of blastomeres and morphology scoring. RESULT(S) Patients undergoing ICSI had a significantly reduced number of embryos with good morphology and cleavage compared with IVF cases. Nevertheless, pregnancy and abortion rates were similar when adjusted by age and number of embryos transferred. Average cleavage status and age were significant predictors of implantation. Women of advanced age had significantly lower embryo cleavage and implantation rates. CONCLUSION(S) [1] The cleaving status of day 3 embryos is a valuable, although limited, indicator of implantation outcome. [2] In vitro fertilization-derived embryos had better cleavage rates and morphology scores than ICSI-derived embryos; however, the implantation potential was similar for both groups. [3] The age-related decline in implantation rate was associated with impaired embryo growth rates.

Clinical significance of human sperm-zona pellucida binding

OBJECTIVE To assess the relationship between sperm morphology and motion parameters and sperm-zona pellucida (ZP) binding capacity under hemizona assay (HZA) conditions and to determine the discriminatory power of the HZA for the prediction of in vitro sperm fertilizing ability. DESIGN Prospectively designed study. SETTING Academic tertiary centers. PATIENT(S) One hundred ninety-six couples undergoing IVF therapy participated in this study. INTERVENTION(S) Hemizona assay and IVF results were determined for each couple. MAIN OUTCOME MEASURE(S) Computerized sperm motion analysis, sperm morphology (strict) criteria), and HZA results were correlated with fertilization outcome. RESULT(S) Among sperm parameters from the original ejaculates, morphology was the best predictor of sperm-ZP binding ability; hyperactivated motility was the best predictor of HZA results after swim-up separation of the motile sperm fractions. The HZA index provided the highest discriminatory power for fertilization success/failure, with an overall accuracy of 86%. CONCLUSION(S) Sperm morphology and hyperactivated motility showed a high correlation with the capacity of sperm to achieve tight binding to the ZP. The excellent positive and negative predictive values of the HZA for fertilization outcome provide additional support for the use of this functional bioassay in the decision-making process within the assisted reproduction setting.

OUTCOMES AFTER INTRAVESICAL BACILLUS CALMETTE-GUERIN ARE NOT AFFECTED BY SUBSTAGING OF HIGH GRADE T1 TRANSITIONAL CELL CARCINOMA

PURPOSE Substaging of T1 bladder tumors into T1a and T1b based on invasion of the tumor superficial to and beyond the muscularis mucosa has been assigned prognostic significance. We determined whether outcomes after intravesical bacillus Calmette-Guerin (BCG) differ between stage T1a and T1b subcategories. MATERIALS AND METHODS Retrospective pathological evaluation of the initial transurethral resection specimens of stage T1 bladder tumors was performed by 2 pathologists. Grade 1, 2 or 3 and stage T1a or T1b were assigned to each case. Followup was from the date of transurethral resection to date of death or the last visit. Kaplan-Meier probability and log rank test were used to evaluate recurrence and progression. RESULTS Substaging was performed in 49 of the 55 patients (89%) with stage T1 disease. Disease was stage T1a in 32 (65%), stage T1b in 17 (35%), grade 3 in 45 (92%) and grade 2 in 4 (8%) cases. Maximum followup was 147 months (median 71) and 28 cases had a minimum of 5 years of followup. Recurrence was noted in 33 cases (67.3%), including 22 stage T1a (69%) and 11 stage T1b (65%), at a median followup of 11.3 and 8.6 months, respectively. Progression to a higher stage of disease was recorded in 12 cases (24.4%), including 7 (22%) stage T1a and 5 (29%) stage T1b, at a median followup of 108 and 120 months, respectively. The difference between T1a and T1b subcategories was not statistically significant in regard to recurrence-free (p = 0.7203) and progression-free (p = 0.574) outcomes. CONCLUSIONS Substaging of T1 tumors did not affect response to BCG in regard to recurrence or progression. Therefore, intravesical BCG is effective for stages T1a and T1b disease.

Parameters that predict nipple involvement in breast cancer.

BACKGROUND Breast conservation therapy has been shown to produce survival rates equivalent to those seen with modified radical mastectomy. Synchronous occult neoplastic involvement of the nipple may lead to incomplete excision of the tumor in patients undergoing breast conservation therapy, possibly leading to recurrence. STUDY DESIGN The charts of 803 breast cancer patients treated between 1990 and 1995 at two teaching hospitals were retrospectively reviewed. The patients were divided into three groups: nipple-positive for malignancy (n = 54), nipple-negative for malignancy (n = 404), and nipple-not-removed (n = 345). Ten different clinical and tumor parameters including age, race, primary tumor location, histologic grade, primary tumor size, nodal involvement, TNM stage, estrogen receptor status, DNA ploidy, and S-phase were examined for the ability to predict cancerous nipple involvement. RESULTS Overall, the rate of nipple positivity was 12%. In univariate analysis pathologic stage, tumor size, lymph node status, histologic grade, and tumor location were significant predictors of positive nipple involvement. Patients with tumors that were stage III or higher were nearly ten times (odds ratio [OR] = 9.8, 95% confidence interval [CI] = 5.5 to 17.7) more likely to have nipple involvement than patients with early-stage tumors. Patients with a tumor size of 4 cm or greater were nearly eight times (OR = 7.8, 95% CI = 4.2 to 14.5) more likely to have nipple involvement than patients with tumor size less than 4 cm. Patients with positive lymph nodes were five times (OR = 5.0, 95% CI = 2.7 to 9.1) more likely to have nipple involvement than patients with negative lymph nodes. Patients with tumors in a central location or that overlapped quadrants were nearly four times (OR = 3.8, 95% CI = 2.2 to 6.8) more likely to have nipple involvement than patients with tumors in other locations. Patients with grade 3 or undifferentiated tumors were three times (OR = 3.0, 95% CI = 1.4 to 6.4) more likely to have nipple involvement than patients with lower grade tumors. In multivariable analysis, stage > or = 3 (OR = 9.2, 95% CI = 4.2 to 20.3) central/ overlap location (OR = 4.1, 95% CI = 2.0 to 8.7) and grade 3 or undifferentiated (OR = 3.1, 95% CI = 1.3 to 7.5) were the only variables that remained significant predictors of nipple involvement. CONCLUSIONS The decision to perform breast conservation surgical procedures with nipple preservation can be difficult, particularly in patients with larger, more centrally located tumors. The multivariable model developed in this study may be useful in predicting the risk of cancerous nipple involvement and selecting appropriate breast conservation patients for nipple preservation.