Francis H. Straus

Association of Diethylstilbestrol Exposure in Utero With Cryptorchidism, Testicular Hypoplasia and Semen Abnormalities

Epididymal cysts and/or hypoplastic testes have been found in 31.5 per cent of 308 men exposed to diethylstilbestrol in utero, compared to 7.8 per cent of 307 placebo-exposed controls. Analyses of the spermatozoa have revealed severe pathological changes (Eliasson score greater than 10) in 134 diethylstilbestrol-exposed men (18 per cent) and 87 placebo-exposed men (8 per cent). Further investigation of the 26 diethylstilbestrol-exposed men with testicular hypoplasia has revealed that 65 per cent had a history of cryptorchidism. Only 1 of the 6 placebo-exposed controls with testicular hypoplasia had a history of testicular maldescent. Although none of our Diekmanns lying-in study group has had carcinoma to date one must keep in mind the reported increased risk of testicular carcinoma in testes that are or were cryptorchid. A 25-year-old man who was not part of the study group was treated recently by us for a testicular carcinoma ( mixed anaplastic seminoma plus embryonal cell carcinoma) and he had a history of diethylstilbestrol exposure in utero and cryptorchidism.

Feminizing Sertoli cell tumors in boys with Peutz-Jeghers syndrome.

We report the pathology findings in two cases of multicentric Sertoli cell testicular tumors in two young boys with probable Peutz-Jeghers syndrome. Four cases of such tumors occurring in boys with Peutz-Jeghers syndrome were previously reported. Each of the two boys reported in this paper had prominent gynecomastia, rapid growth, and advanced bone age. Serum levels of estradiol were markedly elevated. Anti-müllerian hormone was measured in the serum of one of the boys and was in the normal range for age. Bilateral orchiectomy was performed in each case because the neoplastic growth would most likely result in sterility, and curtailment of height potential was threatened from continued elevation of estradiol levels. Microscopically, greatly enlarged seminiferous tubules packed with ovoid Sertoli-like cells were present. Prominent eosinophilic basement membrane surrounded the tubules and intersected between the cells, forming hyalinized ovoid globules and microcalcifications. Ultrastructure revealed lamination of basement membranes surrounding adjacent cells, ovoid cells with abundant cytoplasm, and limited smooth endoplasmic reticulum. Studies of testicular tumor tissue from both case revealed increased transcription of the aromatase cytochrome P450 gene using promoter II, the promoter directing aromatase expression in the normal ovary and testis. The levels of transcripts were comparable to corpus luteum, thus resulting in increased estrogen synthesis. Transcripts specific for placental-type aromatase promoters (1.1 and 1.2) were not detected in significant levels in these tumors.

Osteosclerosis in primary hyperparathyroidism

Osteosclerosis in adults with primary hyperparathyoidism is rare; the usual skeletal manifestation, when presented, is diffuse osteropenia. We describe a patient with generalized osteosclerosis in association with primary hyperparathyroidism. The findings are documented by conventional and fine-detail radiography, absorptiometric bone mineral analysis, quantitative microradiography and histologic examination of bone. The unique features are contrasted with the manifestations recorded in a recently studied group of 87 hyperparathyroid patients. The data presented here support a causal relationship in this patient between parathyroid hormone excess and the development of densely sclerotic bones.

The Use of Collagen‐GAG Membranes in Reconstructive Surgery

ABSTRACT: Porous collagen‐glycosaminoglycan (PCG) membranes with a porous silicone elastomer coating have been useful as a scaffold for dermal replacement in burn victims. Critical physicochemical parameters of these membranes include pore size, cross‐link density, the percentage of glycosaminoglycan, and the degree of banding of the collagen. These factors govern the immunobiological response. Optimizing these parameters can reduce inflammation, scarring, and contraction of wounds grafted with PCG membranes. PCG membranes are currently commercially manufactured (Integra®, Integra Life Sciences, New Jersey) and available for clinical use.

Thiazide-induced parathyroid stimulation

Abstract Twenty dogs were given oral hydrochlorothiazide in varying dosages for periods ranging up to nine months. All dogs showed significant hypercalcemia and hypophosphatemia. In addition, the parathyroid glands of these dogs were enlarged, and many showed areas of histological changes suggestive of hyperactivity. None of these biochemical or morphological alterations were noted in twenty control dogs receiving no thiazides. It is concluded that the thiazide diuretics may cause parathyroid stimulation, and administration of these drugs should be considered in the differential diagnosis of hypercalcemia.

Laparoscopic Pelvic Lymph Node Dissection: A Review of 103 Consecutive Cases

Laparoscopic pelvic lymph node dissection is a recently introduced technique for the surgical evaluation of the regional pelvic lymph nodes in genitourinary malignancies. We report the results of a laparoscopic pelvic lymph node dissection performed on 103 consecutive patients for staging of clinically localized prostatic, bladder and penile carcinomas. In 20 patients (group 1) the adequacy of the laparoscopic pelvic lymph node dissection was evaluated with a subsequent open dissection. In this group 87 to 95% of the lymph nodes within a modified template could be reliably removed laparoscopically. In 73 patients (group 2) laparoscopic pelvic lymph node dissection was performed as a solitary operation. Mean hospitalization was 1.6 +/- 2.4 days, while postoperative narcotic requirements were minimal. Mean operative time for bilateral laparoscopic pelvic lymph node dissection was 156 +/- 41.2 minutes. The overall complication rate in these 2 groups was 13.5%. Group 3 includes 10 patients (9.7% of the total) in whom laparoscopic pelvic lymph node dissection was unsuccessful. The minimally invasive surgical techniques of laparoscopic pelvic lymph node dissection seem to provide adequate staging accuracy in patients with genitourinary neoplasms. The complication rate and recovery period appear to be decreased relative to those for open surgical lymphadenectomy.

Primary Carcinoid Tumor of the Urethra

The first reported case of a carcinoid tumor of the urinary tract is presented. Because of rapid local recurrence and distant spread early radical surgery is recommended. Several methods of palliation of the carcinoid syndrome-surgical, pharmacologic and chemotherapeutic-are discussed.

Selective surface staining of bladder tumors by intravesical methylene blue with enhanced endoscopic identification

Intravesical instillation of methylene blue resulted in selective surface staining of bladder tumors in vivo without staining the background of normal urothelium. Staining of human bladder tumors in vivo was accomplished by the intravesical instillation of 0.1% methylene blue in 0.9% saline through a foley catheter under 20 cm of hydrostatic pressure up to a maximum volume of 400 ml. After 5 minutes contact time, the methylene blue solution was drained, and the bladder was washed with saline. Thereafter, either endoscopic or open surgery was performed. The transitional cell carcinomas in 45 of 48 patients bound methylene blue to the surfaces of the tumors but not to normal urothelium. Higher grade tumors usually bound the dye more extensively than lower grades. The three patients, whose tumors did not bind methylene blue, had received previous chemotherapy, which might account for their being falsely negative. Carcinoma in situ and dysplasia did stain blue. Areas of hyperplasia and cystitis, however, did not bind methylene blue. In vivo intravesical staining with methylene blue has been a simple and safe procedure which has enhanced the endoscopic localization for biopsy and fulguration/resection of transitional cell carcinomas.

Effective gene therapy for medullary thyroid carcinoma using recombinant adenovirus inducing tumor-specific expression of interleukin-12

No satisfactory treatment of metastatic medullary thyroid carcinoma (MTC) is available. Cell-specific gene therapy offers a new approach. We have constructed a recombinant replication-defective adenoviral vector expressing murine interleukin-12 (mIL-12), driven by a modified CALC-I promoter (TCP). This vector (AdTCPmIL-12) includes two separate cassettes encoding mIL-12 p35 or p40 subunit controlled by TCP inserted in the E1 region of adenovirus type 5. In vitro and in vivo reporter gene expression using TCP revealed its cell-specific activity. AdTCPmIL-12-infected rat MTC (rMTC) cells produced high amounts of functional mIL-12 cells in vitro, while other cell lines infected with AdTCPmIL-12 did not. AdTCPmIL-12-transduced rMTC cells completely lost their tumorigenicity in syngenic WAG/Rij rats. Direct injection of 1 × 109 plaque forming units of AdTCPmIL-12 into subcutaneous rMTC tumors in WAG/Rij rats caused tumor regression in over 60% of animals within 20 days. Rats cured of tumors did not develop tumors after re-injection of naive rMTC cells, demonstrating lasting immunity. Treatment with AdTCPmIL-12 of one tumor resulted in regression of an established tumor at a distant site. Moreover, intratumoral or intravenous injection of AdTCPmIL-12 did not induce evident toxicity. These results indicate AdTCPmIL-12 can contribute to effective and less toxic gene therapy of MTC.

Papillary clear cell carcinoma of the thyroid gland

A case of an unusual papillary clear cell carcinoma of the thyroid gland is described. The patient expired 17 days after operative biopsy and thyroxine suppression. Special stains were helpful in differentiating renal cortical carcinoma and parathyroid malignant disease from primary papillary clear cell carcinoma of the thyroid. Ultrastructural features of this tumor may relate to the effects of thyroid stimulating hormone as well as the malignant nature of the tumor.