Angiomyolipoma with regional lymph node involvement and long-term follow-up study.

The first long-term follow-up study of a patient who had renal angiomyolipoma with regional lymph node involvement is reported. The absence of recurrence after 15 years favors the view that regional lymph node involvement represents a multicentric hamartomatous change and is not a metastasis from a malignant renal tumor.

Follow-up study of male and female offspring of DES-exposed mothers.

This follow-up study presents the effects of DES on the genital tract of male and female offspring of mothers who were part of a double-blind, placebo-controlled investigation during 1951 and 1952 aimed at determining the effect of DES on pregnancy. Epididymal cysts, hypotrophic testes, and capsular induration were the more common genital lesions found in 25% of 163 DES-exposed males as compared to 6% in 168 control males. Semen analysis data on 39 subjects of the DES-exposed group and 25 subjects of the control group showed that 26% of the DES-exposed group produced an ejaculate volume under 1.5 ml; no such cases were observed in the control group. The average values for sperm density ant total motile spermatozoa per ejaculate, although in the normal range, were more than two times lower in the DES-exposed group as compared to the controls. A quality score of greater than 10 ("severely pathologic semen") was found in 28% of the DES-exposed group as compared to 0 in the control group. An association of pathologic semen quality with physical abnormalities was found only in the DES-exposed group. Two cases of azoospermia, one without genital abnormalities on physical examination and one with bilateral hypotrophic testes were observed so far in the DES-exposed group. Eighteen percent of 229 DES-exposed female patients had irregular menstrual cycles (oligomenorrhea) as compared to 10% of 136 controls. The history of pregnancy revealed a lower incidence of pregnancy in the DES-exposed group (18%) than in the control group (33%). Circumferential ridges of the vagina and cervix were seen in 40% of 229 DES-exposed females but in none of 136 controls. Colposcopic findings in the vagina revealed adenosis in 66.8% of the DES-exposed females and in 3.6% of the control group. Dysplastic lesions were more prevalent in the vagina and cervix of the DES-exposed subjects. No cases of cancer were observed in either the male or female offspring.

Sandwich radiotherapy (3,000 and 4,500 rads) around radical retropubic prostatectomy for stage C prostatic carcinoma.

Supervoltage external radiotherapy has been sandwiched around radical retropubic prostatectomy as a potentially curative procedure for Stage C or D1 adenocarcinoma of the prostate. Preoperatively, 3,000 rads were delivered to the pelvis and prostate by approximately 18 by 20 cm. AP-PA opposing ports over a three-week period. After three weeks' rest, radical retropubic prostatectomy was done. After three weeks' postoperative recovery, additional radiotherapy was delivered as follows: 2,000 rads to the pelvis and prostatic fossa by AP-PA opposing ports, plus 2,500 rads to the prostatic fossa alone by 360 degree rotation, plus 4,500 rads to the abdominal periaortic-caval lymph node area. Fifteen cases have been followed for up to five and one-half years to date without serious complications of the therapy and without demonstrable recurrent or residual tumor in the pelvis.

Retrograde brush biopsy of the ureter and renal pelvis.

In resonse to the limitations of urinary cytology which have resulted in a high incidence of false negative reports, a technique of retrograde brush biopsy has been developed. This technique aids in the diagnosis of carcinomas of the ureteral and renal collecting systems, thereby permitting earlier and more intensive treatment of malignant lesions of the urinary tract.

Evaluation of renal masses including retrograde renal brushing.

1. The evaluation of renal masses has become an increasingly important topic because of the increasing incidence of kidney cancer, the improved cure rate of renal carcinoma with the proper preoperative diagnosis, and the proliferation in renal mass diagnostic methodology. 2. A variety of benign entities can produce an abnormal renal mass with attendant difficulties in being distinguished from malignant neoplasms. Among these benign lesions are: simple renal cysts, polycystic kidneys, congenital variations in renal size and shape, segmental renal hypertrophy, renal infarcts, intrarenal hematomas, renal hamartomas, renal leiomyomas, renal adenomas, renal angiomas, renal fibrolipomatosis, hydronephrosis of a duplicated collecting system, renal abscesses, and xanthogranulomatous pyelonephritis. 3. Nephrotomography, nephrosonography (ultrasound), adrenalin renal arteriography, selective magnification renal arteriography, renal venography and cavography, lymphangiography, renal scintillation scanning, abnormal levels of enzymes in blood and urine, immunologic studies (circulating antibodies and tumor-associated antigens), percutaneous needle aspirations, and retrograde renal brushing have all increased the diagnostic accuracy of determining the etiology of renal masses. None of these diagnostic procedures is infallible. A judicious combination of procedures gives the most reliable diagnostic results. 4. A search continues for (a) chemical agent(s) or a chemical profile in the blood or urine which is (are) specific for renal carcinoma, but as yet this is an investigational area and not a practical clinical reality.

Structural and functional abnormalities in the sex organs of male offspring of mothers treated with diethylstilbestrol (DES).

The in utero effects of DES (Diethylstilbestrol) on the human male genital tract are reported in this follow-up study of male offspring of DES-treated mothers. Both anatomical and functional abnormalities were significantly greater in the DES-exposed males as compared to control males whose mothers were all participants in a prospective, randomized double blind study of the effects of DES on pregnancy at the Chicago Lying-in Hospital during the early 1950s. Epididymal cysts, hypotrophic testes and capsular induration of the testes were among the more common genital lesions found in 27% of 134 DES-exposed males as compared to a 7% incidence in 119 control males. Spermatozoa analyses revealed severely pathologic changes (Eliasson score greater than 10) in 29% of 28 DES-exposed males and 0% of 18 control males (with or without genital i.e., physical abnormalities). Abnormal findings on physical examination combined with sperm abnormalities (Eliasson score greater than or equal to 5) were found in 29% of DES-exposed males versus 0% of 18 control males. Cytologic examinations did not reveal malignant cells from the following materials: urines before and after prostatic massage or ejaculation, prostatic fluids and aspirates from epididymal cysts.

The influence of bladder fullness on upper urinary tract dimensions and renal excretory function.

Nearly full bladders (375 ml.) produced significantly greater dimensions of the renal calices, pelves and ureters on excretory urograms compared to nearly empty bladders. These dimensions were frequently to the point of being considered pathological dilatations. On planimetry the urographic areas of the pelviocaliceal systems decreased by 43 per cent on the right side and 38 per cent on the left side when the nearly full bladder was compared to the nearly empty bladder in 10 patients. Renal excretory function also was affected by nearly full bladders. Urea clearances after 1 hour were 24 per cent lower and creatinine clearances were 9 per cent lower when starting with a nearly full bladder as compared to starting with an empty bladder. The implications of these findings are of potential significance with respect to 1) interpretation of excretory urograms and 2) chronic urine holding in patients with recurrent urinary tract infections, impaired renal function and/or urolithiasis.

Elevation of the metastable limits and absence of container surface nucleation for calcium oxalate crystallization in a urothelial-lined system as compared to glass containers.

We studied the metastable limits of calcium oxalate supersaturation in glass tubes and in urothelial-lined rat bladders from a solvent system consisting of 0.9 per cent saline. The metastable limit was significantly elevated at 30 min in the urothelial-lined system as compared to the glass-surfaced containers. Heterogeneous nucleation on the container surfaces consistently occurred with the saline solvent in glass tubes as the metastable limit was exceeded. Intraluminal or free-floating crystals (? homogenous nucleation) without container-adherent crystals occurred with the saline solvent in urothelial-lined containers. This study reveals important properties of crystallization in urothelium and emphasizes the potential errors in extrapolating from crystallization studies in vitro in glass containers to crystallization phenomena in biological systems.

Pathological semen and anatomical abnormalities of the genital tract in human male subjects exposed to diethylstilbestrol in utero.

The in utero effects of diethylstilbestrol on the human male genital tract are reported in our followup study of male offspring of mothers treated with diethylstilbestrol. Anatomical and functional abnormalities were significantly greater in male patients exposed to diethylstilbestrol compared to male controls whose mothers were all participants in a prospective, randomized double-blind study on the effects of diethylstilbestrol on pregnancy at our hospital during the early 1950s. Epididymal cysts, hypotrophic testes and capsular induration of the testes were among the more common genital lesions found in more than 25 per cent of 159 male patients exposed to diethylstilbestrol compared to a 6.8 per cent incidence in 161 male controls. Spermatozoal analysis revealed severe pathological changes (Eliasson score more than 10) in 32 per cent of 31 patients exposed to diethylstilbestrol and 0 per cent of 20 male controls. Abnormal findings on physical examination combined with severe sperm abnormalities (Eliasson score more than 10) were found in 23 per cent of the male patients exposed to diethylstilbestrol versus none of the male controls. Cytologic examinations revealed no malignant cells from urine samples before and after prostatic massage or ejaculation, prostatic fluids and aspirates from epididymal cysts.

Povidone-iodine bladder injury in rats and protection with heparin.

Povidone-iodine (Betadine) has been proposed for clinical use in controlling bacterial infections by intravesical instillation in concentrations ranging from 0.1 to 1 per cent. The effects, however, of povidone-iodine on the urothelium of the bladder have not been well studied. We performed experiments to see if injury to the urothelium occurred from intravesical instillation in female rats. Injury was indeed found with concentrations of 0.3 per cent and 1 per cent povidone-iodine, as judged by the observations of increased bladder weight due to edema, histological examination, in vivo bladder staining, crystal adhesion and bacterial adhesion upon the bladder mucosa after povidone-iodine injury. Further study showed that the urothelium recovered in 6 to 7 days after povidone-iodine injury, while a 3rd experiment demonstrated at least partial protection from bacterial and crystal adhesion to povidone-iodine injured urothelium by immediate treatment with heparin instillation in the bladder.

Protective effects of heparin and other sulfated glycosaminoglycans on crystal adhesion to injured urothelium.

Heparin was found to prevent calcium oxalate crystal adhesion to chemically injured rat bladder urothelium. Heparin was the only polysaccharide tested which restored injured urothelium to the functional status of normal, uninjured urothelium with respect to anticrystal adhesion properties. Other sulfated glycosaminoglycans, sulfated polysaccharides and monosaccharides were without restorative or protective effects. 3H-heparin was found to bind to injured urothelium but not to normal urothelium.

Crystallization studies in a urothelial-lined living test tube (the catheterized female rat bladder). I. Calcium oxalate crystal adhesion to the chemically injured rat bladder.

We developed an in vivo technique to study crystallization in a urothelial-lined "living test tube" by employing the catheterized female rat bladder. Calcium oxalate crystals adherent to the bladder urothelium were distinguished from free or intraluminal crystals. Chemical injuries of the urothelium induced by either 0.1 N HCL or 5 per cent Triton X 100 in saline resulted in marked calcium oxalate crystal adhesion to the injured urothelium. Control bladders without urothelial injury remained free of adherent crystals but formed large numbers of small free crystals relatively uniform in size. Histologic and fresh microscopic evaluations of urothelial injury and crystal adhesion are presented.

Further experience with circle tube nephroureterostomy urinary diversion.

Circle tube nephroureterostomy as an alternative method of urinary diversion has now been used in 80 patients, representing a wide variety of clinical problems. The technique offers several advantages over nephrostomy or intubated ureterostomy. Additional extensive experience with the procedure has substantiated the initially favorable impressions.

Experimental cytoxan cystitis and prevention by acetylcysteine.

Cytoxan (cyclophosphamide) given to rats intraperitoneally produced a severe cystitis within four hours with marked inflammatory edema and hemorrhagic ulcerations of the mucosa. An in vivo staining test with methylene blue showed deep staining of the urothelium as has been demonstrated with other types of urothelial injuries; uninjured urothelium does not stain. The cytoxan cystitis is probably not due to cytoxan itself, but to a breakdown product acrolein, an aldehyde appearing in the urine. Rat experiments demonstrated that acrolein instilled intravesically produced a cystitis similar to that found with cytoxan injected intraperitoneally. The cystitis due either to cytoxan or acrolein was prevented by simultaneous intravesical administration of an aldehyde inactivating agent, acetylcysteine (mucomyst).