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Biomedical subjects

H W Herr

Publications and source records attributed to H W Herr.

At least 19 recordsLinked to original sources

Surgical resection of solitary metastases after chemotherapy in patients with nonseminomatous germ cell tumors and elevated serum tumor markers.

BACKGROUND: Chemorefractory metastatic germ cell tumors and elevated tumor markers generally indicate inoperable disease. METHODS: Solitary metastases were resected in 15 patients who had a nonseminomatous germ cell tumor and an elevated alpha-fetoprotein (AFP) and/or human chorionic gonadotropin (HCG) serum level after treatment with cisplatin-based chemotherapy. Patients underwent resection for a residual mass after chemotherapy or for a new solitary metastasis after achieving a complete response (CR) to salvage chemotherapy. RESULTS: Seven patients were disease-free after surgical resection alone. All five patients with an elevated HCG level had a relapse after surgery compared with 3 of 10 patients with only an elevated AFP level. Only 4 of 10 patients with a retroperitoneal metastasis had a relapse after surgery compared with 4 of 5 patients with visceral disease. Eleven of 15 patients overall were disease-free after surgery and subsequent chemotherapy after a relapse. CONCLUSIONS: Surgical resection of a solitary metastasis despite elevated serum tumor markers should be considered in patients who have not had a durable CR to cisplatin-based chemotherapy.

Antineoplastic Combined Chemotherapy Protocols

Intravesical BCG: current results, natural history and implications for urothelial cancer prevention.

Bacillus Calmette-Guerin (BCG) has been shown in randomized trials to be the most effective agent against superficial bladder tumors. BCG therapy prevents or reduces tumor recurrences, abrogates tumor progression and improves survival over surgery alone. The optimal BCG schedule varies among patients, reflecting a heterogeneous tumor population. Multifocality, high grade (G2,3) and T1 tumors are risk factors for tumor recurrence or invasion. Patients presenting with such features are most likely to benefit from BCG. An incomplete response to BCG portends a high risk of tumor progression. Non-responders have a 40-60% risk of developing muscle invasion or metastases within 10 years, compared with 10-15% for BCG responders. Further, 80% of non-responders progress in the bladder within 3-5 years. After 5 years, relapses are more common in the prostate (13-35%) and upper collecting system (15-33%); one-half of these are invasive tumors. This suggests that intense therapy directed at premalignant and early bladder lesions coupled with a chemoprevention strategy designed to protect the whole urothelium will be required to reverse a pan-urothelial tumor diathesis.

Administration, Intravesical

Staging invasive bladder tumors.

Staging of bladder tumors is based primarily on the depth of tumor invasion (T-category). Stage is important to treatment planning and prognosis. The problem is that clinical evaluation by T-category alone often understages the pathologic extent of disease and does not reliably predict treatment results. The current analysis shows that the presence of a mass palpable on bimanual examination is of prognostic value. Incorporating tumor volume with microscopic tumor invasion may enhance the usefulness of clinical staging.

Humans

Distribution of retroperitoneal metastases after chemotherapy in patients with nonseminomatous germ cell tumors.

For patients with advanced nonseminomatous germ cell tumors a retroperitoneal lymph node dissection is routinely performed following chemotherapy if the serum tumor markers have returned to normal. Bilateral retroperitoneal lymph node dissection has been recommended because metastatic deposits may be widespread. The aim of this study was to describe the distribution of retroperitoneal metastases following chemotherapy in patients with nonseminomatous germ cell tumor and determine if the extent of the retroperitoneal lymph node dissection can be modified. We studied 113 patients who had initially bulky retroperitoneal disease and underwent retroperitoneal lymph node dissection following chemotherapy. For the purposes of this study teratoma and malignant germ cell tumor are referred to as tumor. The most common location of tumor was the para-aortic area (91%) in patients with a left primary tumor and the interaortocaval area (78%) in those with a right tumor. Tumor was located outside the boundaries of a modified retroperitoneal lymph node dissection in 14 of the 60 patients with residual disease but the tumor was present within a palpable mass in 6 of these 14 patients. If the residual mass was removed and a modified retroperitoneal lymph node dissection was performed only 9 of the 113 patients (8%) would have tumor left in the retroperitoneum. For a select group of patients with advanced nonseminomatous germ cell tumor treated with chemotherapy, resection of the residual mass combined with modified retroperitoneal lymph node dissection is appropriate.

Humans

Incidence and treatment of complications of bacillus Calmette-Guerin intravesical therapy in superficial bladder cancer.

Intravesical therapy with bacillus Calmette-Guerin (BCG) has proved to be more effective in the prophylaxis and treatment of superficial bladder tumors and carcinoma in situ than most chemotherapeutic agents. Compared to intravesical chemotherapy, instillations with BCG provoke more local and systemic reactions. In addition to the commonly induced granulomatous inflammatory changes in the bladder, which produce irritative symptoms, this therapy may cause systemic side effects varying from mild malaise and fever to, in rare instances, life-threatening or fatal sepsis. We report the incidence and varieties of toxicities in 2,602 patients treated with intravesical BCG. Side effects are classified according to local and systemic toxicity. Treatment options vary according to the severity of toxicity from delaying or withholding instillations to treatment with antituberculous drugs for up to 6 months. In general, 95% of the patients have no serious side effects. Recognition of risk factors, particularly traumatic catheterization or concurrent cystitis, that result in systemic BCG absorption, as well as the prompt and appropriate treatment of early side effects should significantly decrease the incidence of severe toxicity.

Administration, Intravesical

Management of local bacillus Calmette-Guerin failures in superficial bladder cancer.

We attempt to define the treated natural history of patients with superficial bladder tumors (stages Ta, TIS and T1) managed with intravesical bacillus Calmette-Guerin (BCG) to determine the best form of treatment for locally recurrent tumors. The management and survival of 41 patients who failed BCG within the bladder or prostatic urethra and who subsequently were treated with a variety of secondary therapies are reviewed. Our aim was to assess the role of several independent clinical variables on the rate of death from bladder cancer. Of the 41 patients 6 (15%) died. Univariate statistical analysis identified early involvement of the prostatic urethra and the presence of superficially invasive (stage T1) tumor at initial treatment with BCG as factors having an adverse effect on survival. A multivariate statistical model revealed that patients with early prostatic urethral involvement and the presence of superficially invasive (stage T1) tumor at diagnosis had the highest risk of death from bladder cancer. The reason for change in therapy at failure of BCG, stage of the tumor at BCG failure, occurrence of upper tract tumors and early versus delayed radical cystectomy had no impact on survival. The results suggest that not all tumors that recur after BCG are destined to proceed to muscle invasion or metastases, and that some patients may be managed safely by repeated endoscopic resection and intravesical therapy with cystectomy delayed until objective progression is evident. Such an approach can yield survival equal to that in patients treated with early cystectomy and may result in longer intervals of bladder preservation in a select subset of patients who fail BCG locally.

BCG Vaccine

Bacillus Calmette-Guerin therapy for superficial bladder cancer: a 10-year followup.

We report the outcome of 61 patients with superficial bladder tumors who received bacillus Calmette-Guerin (BCG) therapy and were followed for at least 10 years (range 10 to 13 years). A total of 19 patients (31%) remains free of tumor and progression, 17 (28%) had interval superficial recurrences but no progression and 25 (41%) had progression, first identified as muscle invasion in 12, prostatic involvement in 8 or metastasis in 5. Most tumors recurred or progressed within the first 5 years. Of the 61 patients 33 (54%) are disease-free and with an intact bladder, 13 (21%) are alive after cystectomy, 2 (3%) died of other causes, 1 (2%) is alive with metastasis and 12 (20%) died of metastatic urothelial cancer (11 from the bladder or prostate and 1 from an upper tract tumor).

Adult

Adult urological sarcoma.

From July 1982 to December 1989, 43 of 1,583 adults (2.7%) with soft tissue sarcoma admitted to the Memorial Sloan-Kettering Cancer Center (MSKCC) had tumors arising from the urinary tract and male genital tract (urological sarcoma). The most common site of origin of the tumor was paratesticular (14 patients), followed by the prostate/seminal vesicle (12), bladder (10) and kidney (7). The most common histological type was leiomyosarcoma (19 patients), followed by rhabdomyosarcoma (14), liposarcoma (5) and 5 other histological sarcoma categories (angiosarcoma, malignant fibrous histiocytoma, mesenchymoma and 2 undifferentiated sarcomas). Most of the tumors were high grade (86%) and more than half (56%) were greater than 5 cm. in diameter. A total of 9 patients (21%) presented with metastatic disease, 8 of whom had rhabdomyosarcoma. Complete resection with negative microscopic margins was possible in 58% of the patients. Actuarial relapse-free survival for all patients at 3 and 5 years was 55% and 40%, respectively. There were no significant differences in survival based on patient age, sex or histological tumor type. Favorable prognostic variables by univariate analysis included tumor diameter less than 5 cm., low histological grade, paratesticular or bladder tumor site and complete surgical resection. Application of the MSKCC sarcoma staging system, which is based on grade, size, depth and presence or absence of metastasis, was useful to predict survival. In our experience patients with stage 3 (high grade, greater than 5 cm., 15 patients) or stage 4 (metastatic disease, 9 patients) had a combined 3-year relapse-free survival rate of only 26% and they should be considered candidates for adjuvant treatment protocols.

Actuarial Analysis

Transurethral resection in regionally advanced bladder cancer.

Various treatments have proved useful for disease control in some patients with regionally advanced bladder cancer. Transurethral resection may cure some patients with invasive disease, but identifying patients with such potential early in their course is difficult. A restaging transurethral resection helps indicate whether conservative management is feasible and, if not, which operation is appropriate. In some patients, transurethral resection may enhance the response to chemotherapy. Research is needed to identify those tumor characteristics associated with good results of conservative management of regionally advanced bladder cancer.

Administration, Intravesical

Intravesical therapy.

Intravesical therapy is given as an adjunct to transurethral resection of superficial bladder tumors to eradicate existing disease, inhibit tumor recurrence, and prevent progression to muscle invasion or metastasis. Of the available agents, bacillus Calmette-Guerin (BCG) fulfills these goals and appears superior to chemotherapeutic drugs.

Administration, Intravesical

Perirenal lipoma versus renal cell carcinoma.

Pure renal and perirenal lipomas are rare. They arise from renal cortex, capsule, or perirenal tissue, and may be difficult to distinguish from renal adenocarcinomas. We report on a patient who presented with a renal mass that had the radiologic findings suggestive of a renal cell carcinoma, but proved to be a simple lipoma.

Carcinoma, Renal Cell

Renal cell metastases versus liver hemangioma.

We present the case of a man with presumed metastatic renal cell carcinoma based on radiologic examination and weight loss, who refused treatment of any kind for one year. A surgical exploration to control hematuria revealed a Stage I tumor.

Carcinoma, Renal Cell

Progression of stage T1 bladder tumors after intravesical bacillus Calmette-Guerin.

Of 221 patients with superficial bladder tumors (stages Ta, Tis and T1) treated by transurethral resection and an initial 6-week course of intravesical bacillus Calmette-Guerin (BCG) 195 were evaluated after 3 months for local response. Of these patients 17 (8.7%) had a stage T1 tumor, of whom 14 (82%) subsequently had muscle invasion (7), uncontrolled local disease (6) or metastasis (1). The median interval to progression was 8.4 months, which was significantly (p = 0.0001) less than among the other 178 patients with a nonstage T1 lesion or no tumor found at 3 months, of whom 44 (25%) had progression (median more than 5 years). These data suggest that patients with stage T1 tumor 3 months after BCG therapy require additional therapy other than simple tumor resection and meticulous followup.

BCG Vaccine

Preoperative prostate-specific antigen in predicting pathologic stage and grade after radical prostatectomy.

Preoperative serum prostate-specific antigen (PSA) was measured in 63 men who had clinically localized, previously untreated adenocarcinoma of the prostate and underwent subsequent radical prostatectomy and bilateral pelvic lymph node dissection. Pathologic stage and grade were correlated to the serum PSA value. Patients with organ-confined (P1, P2) and extracapsular (P3, P3N +) prostate cancer had elevated preoperative serum PSA levels (greater than 4 ng/mL) in 61 and 90 percent of cases, respectively. Patients with low-grade and high-grade tumor histology had elevated preoperative PSA levels in 62 and 80 percent of cases, respectively. In distinguishing between organ-confined and extracapsular disease with a preoperative serum PSA of 10 ng/mL as a cutoff value, the sensitivity was 68 percent, the specificity was 66 percent, the positive predictive value was 46 percent, and the negative predictive value was 83 percent. Although there was a trend of increasing preoperative serum PSA levels with higher pathologic stage or grade, there was no significant difference in preoperative serum PSA values with pathologic stage and/or grade considered as a group or in determining stage and/or grade preoperatively on an individual basis.

Adenocarcinoma

Patient selection for retroperitoneal lymph node dissection after chemotherapy for nonseminomatous germ cell tumors.

The indications for retroperitoneal lymph node dissection (RPLND) after chemotherapy for nonseminomatous germ cell tumor of the testis vary widely. We reviewed our experience with 122 patients who underwent RPLND within 6 months of receiving cisplatin-based chemotherapy for bulky (greater than 3 cm) retroperitoneal metastases. Pathologic findings were necrotic tissue in 57 (47%), teratoma in 48 (39%), and residual malignancy in 17 (14%). The size of the retroperitoneal mass after chemotherapy (p = 0.001) and the degree of shrinkage that occurred with chemotherapy (p = 0.0001) were both strongly correlated with the histologic findings at RPLND. The presence or absence of teratomatous elements in the pretreatment orchiectomy specimens was only weakly correlated (p = 0.06). Multivariate logistic regression found shrinkage and the size of the residual mass to be independent predictors of finding only necrotic tissue. We were unable to identify preoperatively a group of patients in which some did not have teratoma or malignancy ultimately resected. Of 39 patients who had a residual mass less than 1.5 cm, and 43 patients whose residual mass was less than 1.5 cm or whose mass had shrunk by greater than 90%, 3 had residual malignancy, and 5 had teratoma resected. Among these 8 patients, 7 had prechemotherapy masses greater than 3 cm. Even with stricter criteria, of 17 patients with no testis teratoma initially and a residual mass less than 1.5 cm which had shrunk by greater than 90%, 5 (30%) had teratoma or malignancy resected. Postchemotherapy RPLND is recommended for all patients with a prechemotherapy mass greater than or equal to 3 cm, irrespective of the radiographic findings.

Antineoplastic Combined Chemotherapy Protocols

Local BCG failures in superficial bladder cancer. A multivariate analysis of risk factors influencing survival.

Of 221 patients with superficial bladder cancers treated with intravesical BCG, BCG therapy failed locally within the bladder or prostate in 41 patients. A multivariate analysis was done using data on these local failures to identify clinical variables influencing survival. Patients presenting with T1 tumors which relapsed initially in the prostate were at highest risk of dying of bladder cancer. Cystectomy is justified in such patients. Others with noninvasive local refractory disease can be managed by continued conservative therapy.

Analysis of Variance