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Biomedical subjects

G P Haas

Publications and source records attributed to G P Haas.

At least 19 recordsLinked to original sources

Adoptive immunotherapy of cancer: biological response modifiers and cytotoxic cell therapy.

Immunotherapy has been developed for the treatment of metastatic cancers refractory to conventional therapies. Immunotherapy utilizes immune cells and/or biological response modifiers (BRMs) to induce an anti-tumor response mediated by the patient's immune system. BRMs, including lymphokines and cytokines, are used as single agents or in combination for cancer therapy. Some BRMs, particularly interleukin 2 (IL-2), can activate and expand in vitro lymphocytes with anti-tumor reactivity which will be adoptively transferred to the patient. To enhance the therapeutic effect of immunotherapy, gene therapy is currently under investigation and involves the insertion of cytokine genes in immune cells or in tumor cells. The development and future of cancer immunotherapy will be discussed in this review.

Animals

Accuracy of frozen section examination of testicular tumors.

Benign testicular masses are recognized with increasing frequency and testis-sparing surgery, based on benign frozen section diagnosis, is practiced more often. However, there is a paucity of information in the medical literature regarding the accuracy of frozen section diagnoses of testicular tumors, and misdiagnoses could have dire consequences. We reviewed thirty frozen section examinations that were performed between 1962 and 1991, a period in which five hundred inguinal orchiectomies were performed. The entire testicle was available for histologic evaluation in 26 cases. Frozen sections correctly identified all of twenty-four malignant and two benign testicular masses. This study demonstrates that frozen section examinations can accurately diagnose testicular cancer.

Adult

Synergy of radiation therapy and immunotherapy in murine renal cell carcinoma.

The treatment of metastatic renal cell carcinoma with immunotherapy has resulted in objective anti-tumor responses in 15-30% of patients. To enhance the therapeutic effects of immunotherapy, it is becoming evident that this approach should be combined with other treatment modalities. In this study, a spontaneously metastasizing murine renal adenocarcinoma (Renca), transplanted under the renal capsule, was treated with either radiation therapy, immunotherapy or a combination of both. In order to distinguish between the local and systemic effects of radiation therapy, total body irradiation was compared to irradiation of the tumor-bearing kidney only, or irradiation of the whole mouse with the tumor-bearing kidney shielded. Immunotherapy was administered with interleukin-2 (IL-2) alone or with IL-2 and lymphokine activated killer (LAK) cells. Combined radiation and immunotherapy induced a better anti-tumor response than either modality alone. The best response was obtained by local tumor irradiation and IL-2 therapy and resulted in a significant reduction in primary tumor size, elimination of lung metastases and a significant increase in survival.

Animals

Immunotherapy with interleukin-2 and alpha-interferon in patients with metastatic renal cell cancer with in situ primary cancers: a pilot study.

A total of 12 patients with stage 4 renal cell carcinoma and primary renal tumors in situ was entered into a pilot study using treatment with interleukin-2 and alpha-interferon followed by radical nephrectomy. Of the patients 11 underwent nephrectomy after an initial course of immunotherapy. Ten patients were able to receive a second course of immunotherapy given after nephrectomy. One patient achieved a complete response of lung and mediastinal metastases without any change in the primary renal tumor but after nephrectomy the patient remained in complete remission for greater than 11 months. A total of 3 patients achieved a partial response at some extrarenal sites but they had progression elsewhere. Toxicity was similar to previous experience with this immunotherapy regimen. Therefore, we demonstrated that metastatic tumor regression is possible with primary renal tumors in situ and that aggressive interleukin-2-based immunotherapy can be tolerated in the presence of a large renal tumor.

Adult

Tumor-infiltrating lymphocytes from nonrenal urological malignancies.

Tumor-infiltrating lymphocytes (TIL) were isolated from 15 of 20 surgical specimens of transitional cell carcinoma of the urinary bladder, prostate cancer, testicular cancer, Wilms tumor and adrenal cancer. Expansion was carried out in four different culture conditions, each containing 1000 U/ml interleukin-2: RPMI medium with or without 20% (by volume) of lymphokine-activated killer cell (LAK) supernatant and AIM V medium with or without 20% LAK supernatant. The resultant cell populations were then assayed for cytotoxicity against a variety of autologous and allogeneic tumor targets and phenotypic analysis was performed with fluorescein-labeled monoclonal antibodies. TIL growth was unrelated to the initial percentage of lymphocytes or tumor cells present in the enzymatically dispersed specimens or whether fresh or cryopreserved tissue was utilized. Better growth was seen in AIM V than in RPMI medium (P = 0.013); the beneficial effect of the addition of LAK supernatant to RPMI was indicated (P = 0.065), and the addition of LAK supernatant to AIM V did not improve the ability to culture TIL (P = 0.5) from these cancers. TIL in long-term culture were predominantly CD3+. The ratio of CD4+/CD8+ cells varied with time in culture and culture medium, but most cultures eventually became CD4+. Cells bearing B cell, natural killer cell, and macrophage markers disappeared early in culture. Overall 14/15 TIL samples were lytic against one of the autologous and allogeneic targets tested, but specific lysis against the autologous tumor from which it was derived was seen in only one TIL culture originating from a bladder cancer. Our results suggest that TIL can be expanded to therapeutic levels from a variety of urological malignancies and that their potential role in future therapy should be further explored.

Adult

Preparative cytoreductive surgery in patients with metastatic renal cell carcinoma treated with adoptive immunotherapy with interleukin-2 or interleukin-2 plus lymphokine activated killer cells.

A total of 63 patients with metastatic renal cell carcinoma with the primary kidney tumor in place was accepted as candidates for immunotherapy at the Surgery Branch of the National Cancer Institute. Of the 63 patients 54 underwent nephrectomy and 9 were treated with the primary kidney tumor in place. Many of the patients underwent associated procedures, such as regional lymphadenectomy (11), venacavotomy with extraction of tumor thrombus (9), hepatic resection (2), pulmonary wedge resection (2), cholecystectomy (2), splenectomy (2), distal pancreatectomy (1), omentectomy (1) and contralateral adrenalectomy (1). Of the 54 patients 20 were not able to enter therapy because of tumor-related (17) or other medical (3) reasons that developed between the operation and therapy, while 34 were able to receive immunotherapy postoperatively. The 20 patients who were treated with either high dose interleukin-2 or interleukin-2 plus lymphokine activated killer cells soon postoperatively (mean 2.1 months) were able to tolerate roughly the same amount of interleukin-2 as the 74 who had undergone nephrectomy before referral to our institute and who were treated for a mean of 22 months after nephrectomy. Further studies, including a prospective, randomized trial, will be required to define the role of nephrectomy in patients with advanced renal cell carcinoma before treatment with interleukin-2 based immunotherapies.

Carcinoma, Renal Cell

Clinically occult Leydig cell tumor presenting with gynecomastia.

An occult Leydig cell tumor is described in a patient who presented with gynecomastia. Diagnosis was established by means of testicular ultrasonography and selective testicular venous sampling. The pathophysiology and management of this rare disease entity are discussed.

Adult

A critical evaluation of the Hartmann's procedure.

We reviewed 150 cases of Hartmann's procedure between 1972-86. Indications, rate of colostomy closure, and "diversion colitis" of the rectal pouch are discussed. There were 76 cases performed for diverticulitis. This procedure is easy to perform and carries a low risk. While it removes the diseased bowel segment, it leaves the patient with a colostomy requiring a major operation for closure. When possible, resection with anastomosis is preferable. There are no generally accepted guidelines for performing the Hartmann procedure; it depends on the individual surgeon. Forty three cases were performed for carcinoma. For palliation, it is a good operation; for cure others are preferable. With few exceptions, it is a poor choice for inflammatory bowel disease. In 42 cases of diverticulitis, the colostomy was not closed because of the patient's age, medical or surgical contraindications. Thirteen patients declined the closure. Twelve pouches had to be removed. Mild colitis was found in every pouch examined endoscopically. Severe colitis was found in one patient operated for cancer, in three for diverticulitis, and in 11 for colitis.

Colectomy

Regional lymph node and pulmonary metastases after local hyperthermia of melanomas in C57BL/6 mice.

The effects of local tumor hyperthermia on regional lymph node metastases are inconclusive. We studied the effects of hyperthermia on the incidence of popliteal, femoral, and abdominal lymph node metastases in C57BL/6 mice with primary B16 melanomas (F10 variant) growing subcutaneously in the left foot. Tumors were heated to 42.3, 43.5, and 44.2 degrees C for 90 minutes either 7 days after inoculation of 5 X 10(4) viable cells (microscopic tumor = mic) or when the tumors were approximately 3 mm in diameter (macroscopic tumor = mac). Femoral lymph node metastases occurred in 0/21 control animals and in 8/22 (36%), 11/19 (58%), and 11/17 (65%) animals whose primary tumors were heated to 42.3, 43.5, and 44.2 degrees C, respectively. For all three treatments, the increase in metastases as compared to controls was statistically significant (p less than 0.004, Fisher's exact test). The incidence of abdominal lymph node metastasis was slightly higher in the treated groups than controls. Twenty of 21 (95%) control mice developed popliteal lymph node metastases and hyperthermia-induced increases could not be demonstrated. Fifteen of 21 control mice killed 3 weeks after amputation of tumor-containing leg had pulmonary metastases with an average of 6 +/- 4 (standard deviation) lesions per affected mouse. Pulmonary metastases occurred in 22/22 (100%), 17/19 (89%), and 13/17 (76%) of mice whose tumors were heated to 42.3, 43.5, and 44.2 degrees C, respectively. The numbers of metastases for affected mice were significantly increased compared to controls for tumors heated to 43.5 and 44.2 degrees C (28 +/- 43, 43 +/- 52, 119 +/- 121, p greater than 0.02, p less than 0.006, p less than 0.002, for two sample T-test). While 0/8 mic tumors were cured 5/9 mac tumors heated to 44.2 degrees C disappeared (p less than 0.03, Fisher's exact test) and there was a growth delay in the remaining mice. Mic tumors, heated to 43.5 degrees C, had an accelerated onset of growth while mac tumors heated to this temperature had a slight growth delay. Growth of both mic and mac primary tumors heated to 42.3 degrees C was similar to controls. These results show that therapeutic and subtherapeutic local hyperthermia increases metastases to regional lymph nodes and to lungs even when primary tumor growth rate is partially or totally controlled.

Animals

Cystadenocarcinoma of the rete testis.

We report a rare case of primary adenocarcinoma of the rete testis. The stage A lesion was managed successfully with orchiectomy and retroperitoneal lymph node dissection. The histopathological features, treatment and prognosis of this unusual malignancy are reviewed.

Cystadenocarcinoma

Spontaneous regional lymph node metastases of three variants of the B16 melanoma: relationship to primary tumor size and pulmonary metastases.

We studied the patterns of spontaneous regional lymph node metastases of three variants (F1, F10, and BL6) of the B16 melanoma in C57BL/6 mice and related the incidence to primary tumor size and pulmonary metastases. The incidence of regional lymph node and pulmonary metastases correlated with increasing primary tumor size (p less than or equal to 0.0001). The incidence of pulmonary metastases in mice whose regional lymph nodes did not contain tumor also correlated with increasing primary tumor size (p less than or equal to 0.0001). This propensity for direct hematogenous spread was more apparent in BL6 tumors than in F1 and F10 tumors (p less than or equal to 0.0001). BL6 tumors also metastasized to regional nodes at smaller primary tumor sizes (p less than or equal to 0.04). Heterogeneous variants that metastasize earlier to regional lymphatic and hematogenous sites dictates the natural history of the primary tumor. Whether prophylactic lymphadenectomy for melanomas is therapeutic may depend on dissemination-related phenotypic characteristics.

Animals

Conservative management of epidermoid cyst of testis.

Epidermoid cysts are rare benign tumors of the testicle whose management is controversial. Only 186 cases have been reported, and most were treated with radical orchiectomy. We report 2 cases managed with local excision, and we review the world literature.

Adult

Phototherapy of bladder cancer: dose/effect relationships.

Hematoporphyrin derivative photodynamic therapy has very important clinical applicability in the diagnosis and treatment of transitional cell carcinoma of the bladder, but many aspects of the photodynamic process are yet to be elucidated. This paper investigates the role of dihematoporphyrin ether (DHE) concentration, the duration of light exposure, and the initial size of the tumors in the treatment of a transplantable murine transitional cell tumor system. The best results were noted in tumors less than six mm. in diameter when treated with 15 mg./kg. DHE and exposed to 100 to 180 minutes of visible light. Animals with small initial tumor size combined with higher DHE concentration and longer light exposure time were most likely to show tumor response.

Animals

The high incidence of benign testicular tumors.

Of 2,800 testicular procedures performed at our institution between 1965 and 1985, 233 inguinal explorations were done for suspicion of cancer. Malignancy was present in 161 patients but in 72 cases (31 per cent) benign lesions were found. Despite the benign nature of the lesion 51 of these patients (70 per cent) underwent radical orchiectomy. The incidence of benign testicular tumors is much higher than previously suspected and awareness of this condition should lead to increased testicular preservation in selected cases.

Diagnosis, Differential

Testicular sarcoidosis: case report and review of the literature.

We report a case of clinically evident and histologically proved sarcoidosis of the testicle. Six cases have been reported in the literature. This condition is present most commonly in black patients. Sarcoidosis is known to be associated with malignancy and several cases of coexistent testicular cancer have been reported in the white population. Management should include complete testicular neoplasia diagnostic studies, biopsy of peripheral or mediastinal lymph nodes, and radical orchiectomy in cases of unilateral lesions. Testicular biopsy from the inguinal approach and frozen section evaluation may be considered in bilateral lesions or in the patient with previous orchiectomy for testicular sarcoidosis.

Adult