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Approximately 30% of patients with disseminated testicular cancer who receive platinum-based chemotherapy will experience normalization of tumor markers but have persistent, radiographically evident disease in the retroperitoneum. These patients are usually subjected to retroperitoneal lymph-node dissection (RPLND). In all, 45 of 557 patients (8.1%) undergoing postchemotherapy RPLND at Indiana University Medical Center (IUMC) were found to have neoplastic elements distinct from the classic germ-cell tumor types within their resected specimens. Examples included various sarcomas in 14 patients (3.7%), other nonsarcomatous non-germ-cell cancers in 18 patients (3.2%), and cystic atypical choriocarcinoma in 8 patients (1.4%). No distinct patient characteristic or histologic pattern in the primary tumor was predictive of these unusual findings in the RPLND specimen, although sampling error in the orchiectomy specimen could be the reason for this lack of correlation. Surgical resection of these chemoresistant tumors is potentially curative, with disease-free survival being obtained in 13 of 19 patients (68.4%) with sarcoma, 10 of 18 patients (55.6%) with nonsarcomatous cancers, and 7 of 8 patients (87.5%) with cystic atypical choriocarcinoma at mean follow-up intervals of 30.6, 42.5, and 24.7 months, respectively.

Surgery following chemotherapy for treatment of metastatic testis cancer is reserved for partial remissions with localized tumors considered resectable. After primary chemotherapy, about 90% will have teratoma or necrosis and only 10% will have cancer. The concept of two cycles of post operative chemotherapy in this small group with cancer is supported by a 70% long term cure rate. A more difficult group of patients are those who have had not only primary but also salvage chemotherapy for refractory tumor. About 55% of these patients undergoing post (salvage) chemotherapy RPLND surgery have persistent cancer in the resected specimen. There is no data to support the routine use of repeat salvage chemotherapy post operatively. Of 91 patients presenting for surgery post salvage chemotherapy, 53 were considered completely resected and 36 incompletely resected. Of the 53 realistic candidates for cure with complete resections, 25 were given post operative repeat salvage chemotherapy and 28 received none. 9 (36%) receiving more chemotherapy remained NED and 12 (43%) receiving none remained NED. 12 in each group died of disease. Therefore, there is no data to support routine repeat salvage chemotherapy in patients considered completely resected who had already received salvage chemotherapy pre-operatively. Rather the outcome in this cohort depends more on the completeness of its resectability.

In all, 30% of patients felt to have clinical stage A nonseminomatous testis cancer in fact have pathologic stage B disease. Although patients with clinical stage A nonseminoma currently enjoy a very high change for cure, a better assignment of therapy at diagnosis could lead to an overall decrease in the morbidity of treatment. This study analyzed orchiectomy specimens from 102 patients with clinical stage A nonseminomatous testis cancer, all of whom underwent pathologic staging via retroperitoneal lymph-node dissection (RPLND). Various parameters of the orchiectomy specimen were analyzed to determine wheter or not clinical staging could be improved on the basis of these factors. Statistical analysis resulted in the following model. If the orchiectomy specimen consisted of 100% embryonal carcinoma the patient was classified as being at high risk for retroperitoneal metastasis. In the absence of this finding the aneuploid cell line as determined by flow cytometry was considered. If the percentage of aneuploid cells in the S phase was less than 29% the patient was felt to be at low risk for retroperitoneal metastasis. If this percentage was greater than 29% the patient was classified as being at high risk. Using this paradigm, 77% of pathologic stage A patients and 91% of pathologic stage B patients were correctly classified. The test efficiency was 82%. This pilot study resulted in an interesting model that should be tested prospectively in consecutive patients to determine whether it is clinically useful.

Current clinical staging, which includes the use of serum tumor markers and imaging techniques, fails to identify the 30–40% of clinical stage I (CS I) nonseminomatous germ cell testicular tumor (NSGCT) patients who have occult metastatic disease. Therefore, there is a real clinical need to evaluate new biological parameters of the primary tumor that might be useful as predictors of occult metastatic disease. This study was undertaken to compare quantitative DNA measurements by flow cytometry and image analysis in CS I NSGCT, and to analyze the relevance of these parameters for predicting occult lymph node involvement. Different blocks of formalin-fixed, paraffin-embedded NSGCTs of 62 CS I patients who underwent retroperitoneal lymph node dissection between 1985 and 1989 were prepared according to the Hedley technique, and analyzed by quantitative cytometry. Thirty-six (58.1%) patients had histologically proven lymph node involvement (pathological stage II), whereas 26 (41.9%) patients (pathological stage I) had neither lymph node metastases according to retroperitoneal lymph node dissection (RPLND) specimens nor tumor recurrence during follow-up. Concordant results were found in 76.5% of the samples by both cytometric techniques. For flow cytometry, the percentages of aneuploid cells in the S- and the G2M+S-phase were the most robust predictive parameters for lymph node involvement, whereas for image analysis the 5c exceeding rate (5cER) had the most predictive significance. Based on the experience obtained in this study, both cytometric techniques provide additional information on tumor aggressiveness that might be useful in therapeutic selection of early stage NSGCT patients for either RPLND or surveillance only.

Phosphodiesterase I (PDE I) is an exonuclease capable of hydrolyzing a variety of phosphate ester and pyrophosphate bonds. Cell fractionation and histochemical studies in animal tissues have localized PDE I in the plasma membrane of various epithelia. This suggests a role for the enzyme in active transport. Distribution of PDE I in human tissues has not previously been studied. We have produced a polyclonal antiserum to bovine intestinal PDE I and have demonstrated crossreactivity with the human intestinal enzyme. This polyclonal antiserum was used in PAP immunocytochemistry to localize immunoreactive PDE I in a variety of human tissues. Localization was prominent in the gastrointestinal tract, including the cytoplasm of gastric mucosa parietal cells, cytoplasm of surface epithelium and isolated crypt cells in small intestine, and the colonic epithelial cytoplasm and brush border. Parotid gland acinar cells and scattered ductal cells showed positive cytoplasmic staining. Acinar and scattered pancreatic islet cells contained immunoreactive PDE I, as did Kupffer cells of the liver sinusoids. Immunoreactive PDE I was found in all vascular endothelia. The epithelium of the urinary tract showed extensive immunoreactivity. This included the distal convoluted and collecting tubules of the kidney, and ureteral and bladder urothelium. In previous histochemical studies of animal tissues, no evidence of PDE I activity was noted in male or female reproductive tract. In this study, immunoreactive PDE I was localized to human Sertoli cells and to basal epithelium of the epididymis and prostate acini. Fallopian tube epithelium of female reproductive tract also demonstrated immunoreactive PDI I, as did several cell types in term placenta. Our immunocytochemical results with human tissues differ significantly from previous histochemical studies in animal tissues, principally in the genitourinary system. This may be due in part to the different detection systems employed as well as the higher sensitivity of the immunoperoxidase technique. This underscores the importance of adjunct techniques in tissue surveys. The widespread epithelial distribution of immunoreactive PDE I detected by this polyclonal antibody implies an integral role in cell function, probably in active transport.

Clinical staging in patients with stage I nonseminomatous germ cell tumors (NSGCTs) of the testis fails in 30% to correctly assess pathological stage since microscopic and small-volume retroperitoneal disease is not detectable on computed tomography of the abdomen. Patients staged by retroperitoneal lymph node dissection as pathological stage I incur a distant (chest or serological) tumor relapse rate of 7–15% during follow-up. Recently, we reported on new risk factors as predictors of pathological stage by flow cytometric DNA analysis in clinical stage I patients. These same methods were applied to a group of 14 pathological stage I patients who subsequently had either chest or serological recurrence. The findings in this group of patients were compared with those in a group of 47 pathological stage I patients who did not experience recurrence. In pathological stage I NSGCT patients with distant (chest or serological) tumor relapse, we found by histological evaluation and DNA analysis of the original orchiectomy specimen proliferative tumor activity to be significantly predictive of relapse. Much as proliferative activity of the primary tumor is predictive of retroperitoneal metastasis, it may be a predictor of recurrence in pathological stage I patients.

A competition enzyme-linked immunosorbant assay (CELIA) can be used to determine the amount of antigen needed to immunoabsorb an antiserum. This is demonstrated using both polyclonal and monoclonal antibodies against human amylase. This method is of especial value when the tissue is particularly difficult to obtain, and especially valuable when CELIA has already been completed.