Impact of the mode of detection on outcome in breast cancer patients treated with breast-conserving therapy.

The impact of the mode of detection on outcome in patients with early stage breast cancer treated with breast-conserving therapy (BCT) was reviewed. Between January 1980 and December 1987, 400 cases of stage I and II breast cancer were treated with BCT. All patients underwent an excisional biopsy, external beam irradiation (RT) to the whole breast (45-50 Gy), and a boost to 60 Gy to the tumor bed. One hundred twenty-four cases (31%) were mammographically detected, whereas 276 (69%) were clinically detected. Median follow-up was 9.2 years. Patients whose cancers were detected by mammography more frequently had smaller tumors (90% T1 vs. 62%, p < 0.0001), lower overall disease stage (78% stage I vs. 47%, p < 0.0001), were older at diagnosis (78% >50 years vs. 54%, p < 0.001), less frequently received chemotherapy (8% vs. 21%, p = 0.001), and had an improved disease-free survival (DFS) (80% vs. 70%, p = 0.014), overall survival (OS) (82% vs. 70%, p = 0.005), and cause-specific survival (CSS) (88% vs. 77%, p = 0.003) at 10 years. However, controlling for tumor size, nodal status, and age, no statistically significant differences in the 5- and 10-year actuarial rates of local recurrence (LR), DFS, CSS, or OS were seen based on the mode of detection. Initial mode of detection was the strongest predictor of outcome after a LR. The 3-year DFS rate after LR was significantly better in initially mammographically detected versus clinically detected cases (100% vs. 61%, p = 0.011). Patients with mammographically detected breast cancer generally have smaller tumors and lower overall disease stage at presentation. However, the mode of detection does not independently appear to affect the success of BCT in these patients.

Impact of clinical, pathologic, and treatment-related factors on outcome in patients with locally advanced breast cancer treated with multimodality therapy.

The authors reviewed the experience at their institution treating patients with locally advanced breast cancer using multimodality therapy to identify clinical, pathologic, and treatment-related factors affecting outcome. One hundred patients with locally advanced breast cancer were treated with definitive therapy at William Beaumont Hospital. Three patients had stage IIB disease, 45 patients had stage IIIA disease, and 52 patients had IIIB disease. Thirteen patients had inflammatory breast carcinoma. Seventy-four patients (74%) received trimodality therapy consisting of systemic therapy, radiation therapy, and surgery. Systemic therapy was delivered to 90 patients. Eighty-three patients (83%) received adjuvant radiation therapy. Eighty-five patients underwent mastectomy (85%). Multiple clinical, pathologic, and treatment-related factors were analyzed for their impact on outcome. The median follow-up was 47 months. Overall, the 5-year actuarial rates of local control, disease-free survival, overall survival, and cause-specific survival were 81%, 43%, 53%, and 55%, respectively. The 5-year actuarial cause-specific survival rates for patients with inflammatory breast carcinoma, stage IIIA disease, and stage IIIB disease were 25%, 55%, and 53%, respectively. On multivariate analysis, local control was improved with radiation therapy (p = 0.008) and the absence of inflammatory breast carcinoma (p = 0.008). Disease-free survival was improved with the addition of radiation therapy (p = 0.001) and with less than four positive lymph nodes (p = 0.003). Distant metastasis-free survival was improved in patients without inflammatory breast carcinoma (p = 0.0249) and with less than four involved lymph nodes (p = 0.0135). Cause-specific survival and overall survival were adversely affected by the presence of inflammatory breast carcinoma (p = 0.0135 and p = 0.0325, respectively) or four or more involved lymph nodes (p = 0.0082 and p = 0.012, respectively). Radiation therapy appears to be a critical component in the overall treatment of patients with locally advanced breast cancer by improving the rates of local control and disease-free survival. Other adverse factors for survival include four or more positive lymph nodes and inflammatory breast carcinoma.

Adenocarcinoma of the pancreatic head: a community teaching hospital's experience from 1982 to 1992.

The treatment of adenocarcinoma of the pancreatic head remains variable, with multiple therapeutic options including surgery, biliary stenting, chemotherapy, and radiation therapy. We retrospectively reviewed our experience from 1982 through 1992, which included 160 patients with this diagnosis, evaluating their treatments and outcomes. There were 66 males and 94 females, with a mean age of 70+/-11 years. Forty patients (25%) had no surgery; of these, 27 had no further treatment, whereas 13 received chemotherapy and/or radiation therapy (CT/RT). Of 120 patients who had surgical exploration, only 19 (16%) were resectable for a potential cure. Eleven of these resected patients had no additional therapy, whereas 8 patients received adjuvant CT/RT. Of the 101 unresectable patients, 62 had no further therapy and 39 received CT/RT. Twenty-two patients (14%) had biliary stents placed, 11 in lieu of surgery, 7 preoperatively, and 4 postoperatively. Perioperative mortality was no different for resectable patients (16%) versus unresectable patients (14%). Overall, 90 patients (56%) had one or more complications related to their disease or treatment, with no differences between groups. Median survivals were as follows: no treatment, 1 month; no surgery with CT/RT, 3.5 months; unresectable with no further treatment, 4 months; unresectable with CT/RT, 8 months; resection with no additional treatment, 17 months; and resection with CT/RT, 13 months. Patients with resectable disease had a significantly longer survival than patients who had no surgery (P < 0.001) or who were unresectable at exploration (P < 0.001); the addition of CT/RT after resection had no effect on survival (P = 0.8). The addition of CT/RT significantly increased survival for patients who had no surgery (p = .001) and for patients who were explored but were unresectable (p = .002). In conclusion, despite dismal results, surgery remains the mainstay of treatment for adenocarcinoma of the pancreatic head. Although CT/RT did not increase the median survival after resection, it doubled the median survival after noncurative surgery.

The correlation between the ASTRO Consensus Panel definition of biochemical failure and clinical outcome for patients with prostate cancer treated with external beam irradiation. American Society of Therapeutic Radiology and Oncology.

PURPOSE: We reviewed our institution's experience treating patients with external beam irradiation (RT) to determine if the ASTRO Consensus Panel definition of biochemical failure (BF) following radiation therapy correlates with clinical distant metastases free survival (DMFS), disease-free survival (DFS), cause-specific survival (CSS), and local control (LC). METHODS AND MATERIALS: Between 1/1/87 and 12/31/92, 568 patients with clinically localized prostate cancer received external beam irradiation (RT) using localized prostate fields at William Beaumont Hospital (median total dose 66.6 Gy; range: 60-70.4 Gy). Biochemical failure was defined as three consecutive increases in post-treatment prostate specific antigen (PSA) after achieving a nadir. Biochemical failure was recorded as the time midway between the nadir and the first rising PSA. Five-year actuarial rates of clinical DMFS, DFS, CSS, and LC were calculated for patients who were biochemically controlled (BC) versus those who failed biochemically. Median follow-up was 56 months (range: 24-118 months). RESULTS: Five-year actuarial rates of DMFS, DFS, CSS, and LC were significantly greater in patients who were biochemically controlled versus those who were not (p < 0.001). In patients who were BC, the 5-year actuarial rates of DMFS, DFS, CSS, and LC were 99%, 99%, 98%, and 99% respectively. For patients who failed biochemically, the 5-year actuarial rates of DMFS, DFS, CSS, and LC were 74%, 64%, 89%, and 86% respectively. When stratifying by pretreatment PSA, Gleason score, and T stage these differences remained significant for DMFS, DFS, and CSS. The Cox proportional hazards model demonstrated that BC was the single most important predictor of clinical outcome for DMFS, DFS, CSS, and LC. Pretreatment PSA and Gleason score were also independent predictors of outcome for DMFS and DFS. CONCLUSIONS: The ASTRO Consensus Panel definition of BF following radiation therapy correlates well with clinical DMFS, DFS, and CSS. These findings suggest that the Consensus Panel definition may be a surrogate for clinical progression and survival and should be considered a valid endpoint for separating successful versus unsuccessful treatment. Additional studies with longer follow-up will be needed to corroborate these findings.

Effect of dopamine on renal function after arteriography in patients with pre-existing renal insufficiency.

Contrast media-induced nephropathy is one of the leading causes of hospital-acquired renal failure, occurring most frequently in patients with pre-existing renal insufficiency. We prospectively studied 55 patients with chronic renal insufficiency (serum creatinine concentration 1.4 to 3.5 mg/dl) who underwent abdominal aortography and arteriography of the lower extremities. The patients were randomized into two groups. Group 1, 28 patients, received dopamine 2.5 mcg/kg beginning 1 hour before arteriography and continuing for 12 hours. Group 2 received an equal volume of saline for the same period of time. Serum creatinine and 12-hour creatinine clearance were measured before arteriography and for 4 consecutive days afterward. Acute contrast-induced decrease in renal function was defined as increase in the baseline serum creatinine concentration > or = 0.5 mg/dl. On day 1 postarteriography the serum creatinine increased from baseline .193 mg/dl for controls while the dopamine group decreased slightly from baseline .018 mg/dl (p = 0.002). Excepting day 1 postarteriography, there was no statistical difference between groups, and serum levels for both groups increased linearly from baseline across time (dopamine p = 0.028, control p = 0.025). In patients with pre-arteriography baseline serum levels greater than or equal to 2.0 mg/dl, however, the increase in serum creatinine from baseline levels was consistently and significantly greater in the control group through the fourth day (0.012 < or = p < or = 0.049). Creatinine clearance did not change significantly from baseline after arteriography in the dopamine group (baseline versus days 1 through 4, 0.238 < or = p < or = 0.968); however, the control group showed a significant linear decrease in creatinine clearance from baseline through the fourth day after arteriography (p = 0.016). Dopamine infusion prevented a rise in serum creatinine 24 hours after angiography in patients with pre-existing renal insufficiency, and protected against contrast-induced decrease in renal function in patients whose baseline serum creatinine was > or = 2.0 mg/dl.

Nosocomial Candida glabrata colonization: an epidemiologic study.

Candida glabrata has emerged as an important nosocomial pathogen, yet little is known about its epidemiology. We prospectively followed 98 patients admitted to a medical intensive care unit and the bone marrow transplant unit of a university hospital. Samples from environmental surfaces and the hands of hospital personnel were also cultured. Patients with newly acquired C. glabrata strains were compared to controls who were culture negative for C. glabrata. C. glabrata was recovered from multiple sites from 24 patients and three environmental surfaces. Sixteen patients (17%) acquired C. glabrata after admission to the study units. Significant risk factors for the nosocomial acquisition of C. glabrata were prolonged duration of hospitalization in the unit and prior antimicrobial use. Strain delineation by restriction enzyme analysis revealed 28 different strains of C. glabrata; three strain types were common to nine patients. The environmental isolates were of the same strain type and common to five patients (four patients with newly acquired strains). These results suggest the possibility of exogenous nosocomial acquisition of C. glabrata, including the possible acquisition from the hospital environment. Transmission may be by indirect contact since identical strains of C. glabrata were recovered from patients who were geographically and temporally associated.

Long term results with breast-conserving therapy for patients with early stage breast carcinoma in a community hospital setting.

BACKGROUND: Prospective randomized trials and retrospective reviews from academic centers have documented the success of breast-conserving therapy (BCT) for patients with early stage breast carcinoma. The authors retrospectively reviewed the outcome of BCT for early stage breast carcinoma to determine the success of BCT at the study institution, a 1000-bed community hospital. METHODS: Between January 1980 and December 1987, 400 cases of Stage I and II breast carcinoma were managed with BCT at the study institution. All patients were treated with an excisional biopsy. The axilla was surgically staged in 383 patients (96%). Postoperative treatment was composed of 45-50 gray (Gy) external beam irradiation to the whole breast and a boost to the tumor bed to at least 60 Gy in all patients. The median follow-up of the 292 surviving patients is 118 months. RESULTS: At last follow-up, there were 37 local recurrences for 5- and 10-year actuarial rates of 4% and 10%, respectively. Clinical, pathologic, and treatment-related factors were analyzed for an association with local recurrence. On univariate analysis, patient age < or = 35 years and positive surgical margins were associated with an increased risk of local recurrence. On multivariate analysis, only patient age < or = 35 years remained significant. The 10-year actuarial regional recurrence rate was 5%. The 10-year actuarial cause specific survival rate was 91% and 69% for Stage I and II patients, respectively. CONCLUSIONS: BCT for patients with early stage breast carcinoma in a community hospital setting produces excellent results comparable to contemporary series reported from academic institutions and multiinstitution trials.

The role of regional nodal irradiation in the management of patients with early-stage breast cancer treated with breast-conserving therapy.

PURPOSE: To determine the incidence of regional nodal failure (RNF) and indications for regional nodal irradiation (RNI) in patients with Stage I and II breast cancer treated with breast-conserving therapy (BCT). METHODS AND MATERIALS: Four hundred fifty-six patients with Stage I/II breast cancer were treated with BCT at William Beaumont Hospital. All patients underwent excisional biopsy and 288 (63%) were reexcised. A Level I/II ipsilateral axillary lymph node dissection was performed on 431 patients (95%). Pathologically involved nodes were found in 106 (23%) cases (69 with one to three nodes and 37 with > or = four nodes involved). All patients received whole breast irradiation (median dose 50 Gy) and 415 (91%) were boosted to the tumor bed (median total dose 60.4 Gy). Three hundred and sixty (79%) patients received breast alone irradiation and 96 (21%) also received RNI. The median axilla/supraclavicular fossa dose was 50 Gy. RESULTS: With a median follow-up of 83 months, 15 patients developed a RNF for a 5- and 8-year actuarial rate of 3 and 4%, respectively. The 5- and 8-year actuarial rates of axillary failure (AF) were 0.7 and 1.0%, respectively. The incidence of RNF or AF was not affected by the use of RNI in N0 or N1 patients with one to three positive nodes. Only in patients with four or more positive nodes was there a trend towards improved regional control with RNI (p = 0.09). However, patient numbers were extremely small, and this improvement was limited to a reduction in the rate of failure in the supraclavicular fossa (SCF) (20 vs. 0%, p = 0.04). Multiple clinical, pathologic, and treatment related factors were analyzed for an association with AF. On univariate analysis, AF was associated with the number of lymph nodes excised (p < 0.0001) estrogen receptor status (p = 0.0016), and pathologic node status (p = 0.0021). CONCLUSIONS: Regional nodal failure as the first site of failure is uncommon in patients with early-stage breast cancer treated with BCT with < or = three positive lymph nodes and appears unaffected by RNI. For patients with four or more positive lymph nodes, a trend towards improved RNF was noted with RNI, primarily in the SCF. However, patient numbers were extremely small in all subsets analyzed. Additional studies are needed to further define the need for RNI in these patients and help determine other factors associated with RNF.

Conformal high dose rate iridium-192 boost brachytherapy in locally advanced prostate cancer: superior prostate-specific antigen response compared with external beam treatment.

PURPOSE: Prostate-specific antigen levels are used to judge disease control of prostate cancer. No published data attest to the greater ability of conformal brachytherapy to control disease compared with conventional radiation at a single institution. This report compares the biochemical response rates in patients with stages T2b to T3c prostate cancer treated with conformal brachytherapy boost and external beam radiation with the rates in patients treated with conventional external radiation alone. MATERIALS AND METHODS: From November 1991 through November 1995, 58 patients received 45.6 Gy pelvic external irradiation and three high dose rate iridium-192 conformal boost implants of 5.5 to 6.5 Gy each. They were compared with 278 similarly staged patients treated from January 1987 through December 1991 with external beam radiation to prostate-only fields (median dose 66.6 Gy). No patient received androgen deprivation. Patient outcome was analyzed for biochemical control. Biochemical failure was defined as a prostate-specific antigen level > 1.5 ng/mL and rising on two consecutive values. If serial posttreatment prostate-specific antigen levels were showing a continuous downward trend, failure was not scored. RESULTS: Median follow-up was 43 months for the conventionally treated group and 26 months for the brachytherapy boost group. The median pretreatment prostate-specific antigen level was 14.3 ng/mL for the external-beam-radiation-alone group and 14.0 ng/mL for the brachytherapy boost group. The median Gleason scores were 6 and 7, respectively, for the two groups. The biochemical control rate was significantly higher in the brachytherapy boost treatment group. Three-year actuarial biochemical control rates were 85% versus 52% for the conformally and conventionally treated patients, respectively. In a multivariate analysis, the use of conformal brachytherapy boost and pretreatment prostate-specific antigen level were significant prognostic determinants of biochemical control. The 3-year actuarial rates of biochemical control for conformally versus conventionally treated patients, respectively, were 83% versus 72% for a pretreatment prostate-specific antigen level of 4.1 to 10.0 ng/mL, 85% versus 47% for a prostate-specific antigen level of 10.1 to 20.0 ng/mL, and 89% versus 29% for prostate-specific antigen > 20 ng/mL. When the analysis was limited to patients in both groups with a minimum 12-month follow-up, the brachytherapy boost group continued to show a higher biochemical control rate compared with the conventional radiation group (3-year actuarial rates of 86% vs 53%). DISCUSSION: These preliminary results show a significant improvement in the biochemical response rate with conformal boost brachytherapy and pelvic external radiation compared with conventional radiation alone. These results, coupled with our previously reported acceptable toxicity rates, support the use of this technique.

Ductal carcinoma in situ detected in the mammographic era: an analysis of clinical, pathologic, and treatment-related factors affecting outcome with breast-conserving therapy.

PURPOSE: We reviewed our institution's experience treating predominantly mammographically detected ductal carcinoma in situ (DCIS) with breast-conserving therapy (BCT) to determine if any clinical, pathologic, or treatment-related factors affected outcome. METHODS AND MATERIALS: From January 2, 1980 to January 6, 1992, 107 breasts in 105 patients were treated with BCT at William Beaumont Hospital, Royal Oak, MI. All patients underwent at least an excisional biopsy and 70 patients (65%) were reexcised. All patients received whole-breast irradiation to a median dose of 50.4 Gy (range 43.1 to 56.0 Gy). Ninety-nine patients (93%) received a supplemental boost to the tumor bed for a median total dose of 60.4 Gy (range 59.1 to 71.8 Gy) using either photons (2 patients), electrons (69 patients), or an interstitial implant (28 patients). RESULTS: With a median follow-up of 78 months, 10 patients have failed in the treated breast for a 5- and 10-year actuarial local control rate of 91.2 and 89.8%, respectively. Thirteen percent of the population have been followed for 10 years or more. Three recurrences were pure DCIS, and seven were invasive. All patients were salvaged with mastectomy. Nine patients remain without evidence of disease a median of 30.6 months after surgery. One patient failed distantly 36 months after local recurrence for an ultimate cause specific survival of 99%. Potential clinical (age, mammographic findings, method of detection, etc.), pathologic (nuclear grade, margins, etc.), and treatment-related factors (dose, boost technique, reexcision status, etc.) affecting outcome were analyzed. No variable was found to be associated with an ipsilateral breast tumor recurrence. However, when only recurrences that occurred within or immediately adjacent to the lumpectomy cavity were analyzed, both margin status and the extent of cancerization of lobules (COL) near the surgical margin were associated with the development of a local recurrence. CONCLUSIONS: Patients treated with BCT for predominantly mammographically detected DCIS achieve excellent rates of local control and overall survival. Both margin status and the extent of COL near the surgical margin appear to be associated with recurrences within or immediately adjacent to the lumpectomy cavity. These data suggest that careful attention to the completeness of surgical resection of DCIS is an important determinant of outcome.

An analysis of clinical and treatment related prognostic factors on outcome using biochemical control as an end-point in patients with prostate cancer treated with external beam irradiation.

PURPOSE: We reviewed our institution's experience in treating patients with clinically localized prostate cancer with external beam irradiation (RT) to determine if previously analyzed clinical and treatment related prognostic factors affected outcome when biochemical control was used as an end-point to evaluate results. MATERIALS AND METHODS: Between 1 January 1987 and 31 December 1991, 470 patients with clinically localized prostate cancer were treated with external beam RT using localized prostate fields at William Beaumont Hospital. Biochemical control was defined as PSA nadir < or =1.5 ng/ml within 1 year of treatment. After achieving nadir, if two consecutive increases of PSA were noted, the patient was scored a failure at the time of the first increase. Prognostic factors, including the total number of days in treatment, the method of diagnosis, a history of any pretreatment transurethral resection of the prostate (TURP) and the type of boost were analyzed. RESULTS: Median follow-up was 48 months. No statistically significant difference in rates of biochemical control were noted for treatment time, overall time (date of biopsy to completion of RT), history of any pretreatment TURP, history of diagnosis by TURP, or boost techniques. Patients diagnosed by TURP had a significant improvement in the overall rate of biochemical control (P < 0.03) compared to transrectal/transperineal biopsy. The 5-year actuarial rates were 58 versus 39%, respectively. This improvement was not evident when pretreatment PSA, T stage, or Gleason score were controlled for. On multivariate analysis, no variable was associated with outcome. When analysis was limited to a more favorable group of patients (T1/T2 tumors, pretreatment PSA < or =20 ng/ml and Gleason score <7), none of these variables were significantly predictive of biochemical control when controlling for pretreatment PSA, T stage and Gleason score. CONCLUSIONS: No significant effect of treatment time, overall time, pretreatment TURP, or boost technique was noted on outcome in patients treated with conventional external beam irradiation when biochemical control was used as the end-point to evaluate results.

The impact of temporary iodine-125 interstitial implant boost in the primary management of squamous cell carcinoma of the oropharynx.

BACKGROUND: To define the impact of interstitial boost of the oropharynx on local control and complications using iodine-125 (I-125) brachytherapy. METHODS: Between October 1986 and September 1991, 19 patients with cancer of the oropharynx received treatment at William Beaumont Hospital. Primary tumors consisted of 13 base of tongue, 4 tonsillar, and 2 pharyngeal wall lesions. All patients received 45-66 Gy (median, 54 Gy) external beam irradiation to the primary and regional nodes, followed by an interstitial implant of 22-32 Gy (median, 25 Gy) with I-125. RESULTS: Median follow-up was 58 months (range, 12-89 months). Three patients failed within the tumor bed, for a 5-year actuarial rate of local control of 83% (T1/T2, 82%; T3/T4, 86%). Two of the three local failures were salvaged surgically, for an overall 5-year actuarial local control rate of 94%. The 5-year actuarial overall survival rate was 64%. Complications included one case of soft tissue ulceration and two cases of osteoradionecrosis, all managed conservatively. CONCLUSIONS: Patients with cancer of the oropharynx judged to be candidates for boosts with interstitial implants can be effectively treated with I-125. Local control was excellent, and complications were minimal.

Long-term outcome with interstitial brachytherapy in the management of patients with early-stage breast cancer treated with breast-conserving therapy.

PURPOSE: We reviewed our institution's experience with interstitial implant boosts to determine their long-term impact on local control and cosmetic results. METHODS AND MATERIALS: Between January 1, 1980 and December 31, 1987, 390 women with 400 cases of Stage I and II breast cancer were managed with breast-conserving therapy (BCT) at William Beaumont Hospital. All patients were treated with an excisional biopsy and 253 (63%) underwent reexcision. Radiation consisted of 45-50 Gy external beam irradiation to the whole breast followed by a boost to the tumor bed to at least 60 Gy using either electrons [108], photons [15], or an interstitial implant [277] with either 192Ir [190] or 125I [87]. Long-term local control and cosmetic outcome were assessed and contrasted between patients boosted with either interstitial implants, electrons, or photons. RESULTS: With a median follow-up of 81 months, 25 patients have recurred in the treated breast for a 5- and 8-year actuarial rate of local recurrence of 4 and 8%, respectively. There were no statistically significant differences in the 5- or 8-year actuarial rates of local recurrence using either electrons, photons, or an interstitial implant. Greater than 90% of patients obtained a good or excellent cosmetic result, and no statistically significant differences in cosmetic outcome were seen whether electrons, photons, or implants were used. CONCLUSIONS: We conclude that patients with Stage I and II breast cancer undergoing BCT and judged to be candidates for boosts can be effectively managed with LDR interstitial brachytherapy. Long-term local control and cosmetic outcome are excellent and similar to patients boosted with either electrons or photons.

Assessing the variability of outcome for patients treated with localized prostate irradiation using different definitions of biochemical control.

PURPOSE: Biochemical control using serial posttreatment serum prostate specific antigen (PSA) levels is being increasingly used to assess treatment efficacy for localized prostate cancer. However, no standardized definition of biochemical control has been established. We reviewed our experience treating patients with localized prostate cancer and applied three different commonly used definitions of biochemical control to determine if differences in therapeutic outcome would be observed. METHODS AND MATERIALS: Between January 1987 and December 1991, 480 patients with clinically localized prostate cancer received external beam irradiation (RT) using localized prostate fields at William Beaumont Hospital. The median dose to the prostate was 66.6 Gy (range 58-70.4) using a four-field or arc technique. Pretreatment and posttreatment serum PSA levels were recorded. Over 86% (414 of 480) of patients had a pretreatment PSA level available. Three different definitions of biochemical control were used: (a) PSA nadir < 1 ng/ml within 1 year of treatment completion. After achieving nadir, if two consecutive increases of PSA were noted, the patient was scored a failure at the time of the first increase; (b) PSA nadir < 1.5 ng/ml within 1 year of treatment completion. After achieving nadir, if two consecutive increases of PSA were noted, the patient was scored a failure at the time of the first increase; (c) Posttreatment PSA nadir < 4 ng/ml without a time limit. Once the nadir was achieved, if it did not rise above normal the patient was considered to be biochemically controlled. Clinical local control was defined as no palpable prostate nodularity beyond 18 months, no new prostate nodularity, or a negative prostate biopsy. RESULTS: Median follow-up was 48 months (range 3-112). Pretreatment PSA values were correlated with treatment outcome using the three definitions of biochemical control as well as clinical local control. Pretreatment PSA values were stratified into five groups (Group 1: PSA < 4; Group 2: PSA 4-10; Group 3: PSA 10-15; Group 4: PSA 15-20; and Group 5: PSA > 20), and 5-year actuarial rates of biochemical control were calculated using the three biochemical control and one clinical local control definitions. For Group 1, 5-year actuarial rates of biochemical control were 84%, 90%, 91%, and 96% for Definitions 1-3 and clinical local control, respectively. For Group 2, 5-year actuarial control rates were 45%, 54%, 74%, and 92% for the four definitions, respectively. For Group 3, 5-year actuarial control rates were 26%, 31%, 63%, and 100% for the four definitions, respectively. For Group 4, 5-year actuarial control rates were 24%, 24%, 50%, and 100% for the four definitions, respectively. Finally, for Group 5, 5-year actuarial control rates were 5%, 14%, 15%, and 89% for the four definitions, respectively. Depending on the definition used, statistically significant differences overall in outcome rates were observed. Differences between all four definitions for all pairwise comparisons ranged from 5 to 53% (p < 0.001). CONCLUSION: When different definitions of biochemical control are used in assessing treatment outcome, significantly different rates of success are noted. Until a standardized definition of biochemical control is adopted, differences in treatment outcome cannot be meaningfully compared.

Excellent functional outcome in patients with squamous cell carcinoma of the base of tongue treated with external irradiation and interstitial iodine 125 boost.

BACKGROUND: Local control, functional outcome, and complications in patients with carcinoma of the base of tongue (BOT) were analyzed to assess the impact of interstitial implant boost with I-125 seeds. METHODS: Between December 1986 and May 1995, 16 patients with squamous cell carcinoma of the BOT received treatment at the William Beaumont Hospital and 4 received treatment at the Northern Virginia Cancer Center. The primary tumor classification for this group consisted of T1/T2-11 patients, T3/T4-9 patients. All patients initially received 50.4-66.6 Gray (Gy) (median: 54 Gy) external beam irradiation to the primary site and regional lymph nodes followed by an interstitial implant boost 2 to 3 weeks later. Implant dose ranged from 20 to 32 Gy (median: 27 Gy). The implanted volume included the tumor and glossotonsillar sulcus in all patients and the pharyngeal wall or tonsil in select cases. RESULTS: Median follow-up was 47 months (range, 6-88 mos). Two patients have failed within the tumor bed (T2 and T4) for a 5-year actuarial local control rate of 88%. The T2 patient was salvaged surgically, for an overall 5-year actuarial local control rate of 93%. No patients have relapsed within the neck as the only or first site of failure. The 5-year actuarial overall survival rate was 72%. Complications included three cases of exposed bone and one case of cranial nerve XII palsy. All complications were managed conservatively. Excellent to good functional outcome, including speech and swallowing, was preserved in 18 of the 20 patients. CONCLUSIONS: Patients with cancer of the BOT can be treated effectively with an interstitial boost utilizing I-125 seeds. Overall, local control is excellent and complications are minimal. Of greatest significance, organ preservation with excellent understandability of speech and diet tolerance was achieved in 90% of the patients.

Patient-controlled analgesia versus patient-controlled analgesia plus continuous infusion after hip replacement surgery.

OBJECTIVE: To compare the efficacy and adverse effect profile of patient-controlled analgesia (PCA) versus PCA plus continuous infusion (PCACI) after hip replacement surgery. DESIGN: Prospective, randomized, open pilot study. SETTING: Large teaching institution. PARTICIPANTS: Thirty-four patients undergoing hip replacement or revision of hip replacement surgery. INTERVENTIONS: Patients were randomized to receive PCA morphine: 1 mg with 6-minute lockout, or PCACI, using the same dose, with a 0.5-1 mg/h continuous infusion. Pain intensity, sedation, narcotic use, injection/attempt ratio (I/A), and adverse effects were assessed. RESULTS: No significant differences in pain intensity were identified. Morphine use was not different between groups: PCA 61.8 +/- 35.0 and PCACI 74.2 +/- 54.9 mg (p =0.394). A trend toward an increased 12-hour I/A ratio was evident in the PCACI group: PCA 0.73 +/- 0.18 and PCACI 0.86 +/- 0.17 (p =0.073). Patient-reported adverse effects, sedation, and inability to sleep secondary to pain occurred similarly. Eight of 18 PCACI patients required discontinuation of either the continuous infusion mode or of PCA therapy entirely secondary to adverse effects. CONCLUSIONS: When compared with PCA therapy, PCACI was not associated with improved pain control and more patients receiving PCACI required discontinuation of therapy secondary to adverse effects.

Levels of hepatitis C virus RNA and liver histology in chronic type C hepatitis.

BACKGROUND: The clinical and pathologic significance of quantitative serum hepatitis C virus (HCV) RNA levels in patients with chronic type C hepatitis is unknown. The aim of this study was to determine whether serum levels of HCV RNA were associated with mode of viral transmission or with histological severity of liver disease. METHODS: A branched DNA signal amplification assay for HCV RNA was done on the sera of 127 patients with well-defined risk factors for viral hepatitis. Seventy persons acquired HCV infection by blood transfusion and 57 via tattoo application or former intravenous drug use. Group I included 42 patients with chronic persistent hepatitis, group II consisted of 39 patients with chronic active hepatitis, and group III included 40 individuals whose liver biopsies showed both chronic active hepatitis and cirrhosis, as well as six patients with clinically decompensated cirrhosis. RESULTS: The median HCV RNA level [equivalents/ml (eq/ml) x 10(5)] for patients who acquired infection from transfusion [73.5 x 10(5) (eq/ml)] was not significantly different from that of patients who reported prior intravenous drug use [50 x 10(5) eq/ml] (p = 0.283). The median HCV RNA level for groups I, II, and III was 29.5, 76, and 71, respectively. Group I differed significantly from groups II and III combined (median = 73) (p = 0.02). No difference was noted between group II and group III (p = 0.947). Age did not correlate with level of viremia (r2 = 0.01). No relationship was found between serum alanine aminotransferase and the level of viremia (p = 0.52). Multivariate analysis showed that only the histological severity of the disease proved to be predictive of HCV RNA level (p = 0.04). CONCLUSION: The lowest levels of hepatitis C viremia are, in general, associated with minimal liver disease. Overall, histological severity of chronic hepatitis C infection best predicts HCV RNA levels.

Preoperative fluorescein angiographic features of surgically removed idiopathic epiretinal membranes.

PURPOSE: To determine whether preoperative fluorescein angiograms can be used to predict visual prognosis in eyes undergoing surgical removal of idiopathic epiretinal membranes. METHODS: A retrospective study of preoperative fluorescein angiographic findings in cases of idiopathic epimacular membrane removal during vitreous surgery was conducted. Of 422 consecutive cases, 229 met the criteria for minimum follow-up period of 6 months. Angiograms from these 229 cases were analyzed in a standardized, masked fashion for macular edema, retinal vascular distortion, and contraction of the foveal avascular zone. RESULTS: Visual improvement was greatest in 7 eyes (3%) with the most severe degree of macular edema (P = 0.0215). No difference in visual outcome was noted between eyes with less severe macular edema or no macular edema. Change in visual acuity was not associated with the extent of retinal vascular distortion (P = 0.477) or contraction of the foveal avascular zone (P = 0.248). CONCLUSION: The presence of macular edema on preoperative fluorescein angiography is not predictive of a poor visual outcome in eyes undergoing surgery for idiopathic epiretinal membranes. In general, preoperative fluorescein angiography is not useful in predicting visual prognosis in these cases.

Estimating creatinine clearance in elderly patients with low serum creatinine concentrations.

The accuracy of creatinine clearance (CLcr) estimates generated for elderly patients with a low serum creatinine (SCr) concentration when the SCr concentration was rounded to 1.0 mg/dL was evaluated, and daily aminoglycoside dosages calculated with CLcr estimates based on the actual and the rounded SCr concentrations were compared with the actual dosage required as determined by aminoglycoside concentration measurements. Twenty-four-hour urine collections were obtained from elderly hospitalized patients with stable renal function, and CLcr was measured. SCr concentrations were measured at baseline, during urine collection, and after urine collection. CLcr was calculated twice with each of seven methods, once by using the actual SCr concentration and once by rounding the SCr concentration to 1.0 mg/dL. Rounding the SCr concentration to 1.0 mg/dL resulted in significant underestimation of CLcr by all seven methods. The Cockcroft-Gault equation used with ideal body weight and the rounded SCr concentration resulted in the largest bias. For six of the seven methods, bias was greater and precision less when SCr concentrations of < 0.7 mg/dL were rounded than when SCr concentrations of > or = 0.7 mg/dL were rounded. The Bjornsson method used with the actual SCr concentration appeared to offer the best combination of low bias and high precision. The required aminoglycoside dosage was significantly underestimated when the rounded SCr concentration was used. In elderly patients with low SCr concentrations, rounding the SCr concentration to 1.0 mg/dL led to underestimates of both CLcr and the correct aminoglycoside dosage.