[Aftercare of urological tumors---why and how?].
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Aftercare↗
Biomedical subjects
K P Dieckmann
Publications and source records attributed to K P Dieckmann.
European consensus on diagnosis and treatment of germ cell cancer: a report of the European Germ Cell Cancer Consensus Group (EGCCCG).
Germ cell tumour is the most frequent malignant tumour type in young men with a 100% rise in the incidence every 20 years. Despite this, the high sensitivity of germ cell tumours to platinum-based chemotherapy, together with radiation and surgical measures, leads to the high cure rate of > or = 99% in early stages and 90%, 75-80% and 50% in advanced disease with 'good', 'intermediate' and 'poor' prognostic criteria (IGCCCG classification), respectively. The high cure rate in patients with limited metastatic disease allows the reduction of overall treatment load, and therefore less acute and long-term toxicity, e.g. organ sparing surgery for specific cases, reduced dose and treatment volume of irradiation or substitution of node dissection by surveillance or adjuvant chemotherapy according to the presence or absence of vascular invasion. Thus, different treatment options according to prognostic factors including histology, stage and patient factors and possibilities of the treating centre as well may be used to define the treatment strategy which is definitively chosen for an individual patient. However, this strategy of reduction of treatment load as well as the treatment itself require very high expertise of the treating physician with careful management and follow-up and thorough cooperation by the patient as well to maintain the high rate for cure. Treatment decisions must be based on the available evidence which has been the basis for this consensus guideline delivering a clear proposal for diagnostic and treatment measures in each stage of gonadal and extragonadal germ cell tumour and individual clinical situations. Since this guideline is based on the highest evidence level available today, a deviation from these proposals should be a rare and justified exception.
Europe↗
[Management of testicular intraepithelial neoplasia (TIN)--a review based on the principles of evidence-based medicine].
Testicular intraepithelial neoplasia (TIN; also called carcinoma in situ of the testis) is the uniform precursor of testicular germ cell tumors. There is general agreement on the biological significance of TIN, however, the treatment is still a matter of dispute. The present review summarizes the treatment options currently available. In general, the management of TIN has to be adapted to the particular clinical situation of the patient. Eradication of TIN usually implies the loss of fertility. Therefore, fertility aspects should be considered before any kind of treatment is employed. Usually, patients with TIN have only small residual potential of fertility. Nonetheless, individual patients may qualify for sperm banking or cryopreservation of testicular tissue for future sperm extraction (TESE) and assisted fertilization. The most common clinical situation is the case of contralateral TIN in the presence of unilateral testicular cancer. Low dose radiotherapy to the testis with 18 Gy is the standard management option in these patients. The same procedure may be applied to solitary testicles after partial orchiectomy for germ cell tumors. During follow-up, testosterone levels should be evaluated every six months. If chemotherapy is required due to metastatic disease of the primary tumor management of TIN should be deferred. After chemotherapy 30% of TIN cases will persist and approximately 42% will recur in the later course. Repeat biopsy should be done six months after completion of chemotherapy or later. Only in cases with persistent TIN additional radiotherapy should be administered. If one testicle is afflicted with TIN while the other testis is in healthy condition (conceivable in infertility cases or patients with primary extragonadal germ cell tumors), then the TIN-bearing testis should be excised. Radiotherapy is not feasible in these cases because of shielding problems with the healthy testis.
Biopsy↗
How valid is the prenatal estrogen excess hypothesis of testicular germ cell cancer? A case control study on hormone-related factors.
PURPOSE/AIMS: The prenatal estrogen excess hypothesis postulates abnormally high estrogen levels during pregnancy which predispose the developing gonad to testicular germ cell cancer (GCT) in adulthood. As no direct measurements are possible to support this hypothesis, evidence must come from clinical and epidemiological observations. The present study looked to surrogate parameters that purportedly point to high estrogenic influence in utero. METHODS/PATIENTS: In a case-control study design, 418 cases with GCT were compared to 636 controls having fractures, injuries or nephrolithiasis. A second comparison was done with 120 men suffering from malignant melanoma. The following factors were investigated: maternal and paternal age at birth of proband, birth-order, distribution of brothers and sisters in sibs of patients, sibship size, status of being a twin, status of being a singleton child, handedness, and frequency of breast cancer in mothers and sisters. RESULTS: Status of being a twin was significantly associated with GCT risk (OR 2.41; 95% CI 1.04- 5.63) if compared to men with fractures or stones. Comparison with melanoma controls showed only a nonsignificant trend. Frequency of breast cancer was insignificantly higher in mothers of GCT patients. Maternal age above 30 years was associated with decreased risk of GCT, which is contradictory to the hypothesis. No other parameter was significantly different in cases and controls. CONCLUSION: The present investigation failed to produce evidence for the estrogen excess hypothesis. Obviously, the parameters tested are only weak indicators of estrogenic influence during embryogenesis. Thus, the sample size and statistical power of the trial might have been too low to show any significant association. But, assessing the negative results of this study in light of equally negative results in previous investigations, the estrogen excess hypothesis still remains to be hypothetic.
Adult↗
Renal actinomycosis mimicking renal carcinoma.
The case of a 52-year-old man is reported who presented with night sweats and slight debilitation. Upon CT scan a left-sided renal mass with centrally liquefied areas was detected. The patient underwent nephrectomy for suspected renal cancer with central necrosis. Histologically, the diagnosis of renal actinomycosis was established based on the detection of sulphur granules. Actinomyces israelii is an anaerobic gram-positive bacterium that may cause localized tumour-like infections mainly in the craniocervical region and exceptionally retroperitoneally. Renal actinomycosis is a rare differential diagnosis of renal masses. As nephrectomy may prove hazardous in these cases, the diagnosis should be attempted pre-operatively by ultrasound-guided aspiration and consecutive antibiotic treatment. In selected cases surgery could be avoided at all.
Actinomycosis↗
Re: Malignant germ cell tumor of the contralateral testis after radiotherapy for testicular intraepithelial neoplasia.
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Carcinoma in Situ↗
[Interdisciplinary consensus on diagnosis and therapy of testicular tumors. Results of an update conference based on evidence-based medicine. German Testicular Cancer study Group (GTCSG)].
BACKGROUND: An "Interdisciplinary Consensus Statement on the Diagnosis and Therapy of Testicular Tumors" was prepared in 1996 by the "Interdisciplinary Testicular Tumor Working Group" (IAH) with input from representatives from diagnostic and therapeutic disciplines of various working groups of the German Cancer Society (Strahlenther Onkol 1997;173:397-406). In 1998 the IAH met again together with the "Testicular Tumor Working Party" of the Urooncology Working Group (AUO) and formed the "German Testicular Cancer Study Group" (GTCSG). Defined and accepted interdisciplinary standards from the initial meeting were revised based on current scientific developments and clinical results. This cooperating effort increased the quality of the initial recommendations and helped to put the recommendations for diagnosing and treating testicular tumor on a broader scientific basis. METHODS: According to the principles of "evidence-based medicine" (EBM), the Consensus from 1996 was modified, based on the current level of evidence from the published literature. The methodological process and evaluation criteria used were that of the "Cochrane Collaboration". RESULTS: An "Interdisciplinary Update Consensus Statement" summarizes and defines the diagnostic and therapeutic standards according to the current scientific practices in testicular cancer. For 21 separate areas scientifically based decision criteria are suggested. For treatment areas where more than one option exist without a consensus being reached for a preferred strategy, such as in seminoma in clinical Stage I or in non-seminoma Stages CS I or CS IIA/B, all acceptable alternative strategies with their respective advantages and disadvantages are presented. This "Interdisciplinary Update Consensus" was presented at the 24th National Congress of the German Cancer Society on March 21st and subsequently evaluated and approved by the various German scientific medical societies.
Evidence-Based Medicine↗
[Contralateral biopsy in testicular tumor. A plea in favor of the procedure].
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Biopsy↗
Adjuvant treatment of clinical stage I seminoma: is a single course of carboplatin sufficient?
OBJECTIVES: Adjuvant radiotherapy produces excellent disease-free rates in clinical Stage I seminoma. However, concern is growing about side effects and late hazards of this treatment. Carboplatin has been suggested to supplant radiotherapy. To date, there is little experience with this drug in the adjuvant treatment of seminoma. In particular, it is unclear whether one or two courses should be administered. METHODS: In a nonrandomized study, 125 patients with pure clinical Stage I seminoma were given adjuvant carboplatin treatment (400 mg/m2). Ninety-three patients received one course and 32 two courses. The median follow-up time was 48 months. To assess gonadal toxicity, serial measurements of follicle-stimulating hormone (FSH) levels were done. To assess myelotoxicity, platelet counts at 3 and 4 weeks after treatment were monitored. RESULTS: There were no relapses after two courses of carboplatin. After one course of carboplatin, eight relapses occurred (8.6%; 95% confidence interval [CI] 3.79% to 16.2%). All the relapses were located in the para-aortic region, and all the patients were rescued with cisplatin-based chemotherapy. The median time to recurrence was 16 months. The 5-year actuarial progression-free survival rate after one course was 91.1% (95% CI 85.25% to 97.01%). Younger patients (age groups: less than 30 years and 31 to 38 years) had relapses more frequently (P = 0.038) than those in the older age group (greater than 38 years). After 3 weeks, 32% of the patients had platelet counts below 150/nL. The median FSH level increased immediately after treatment, reaching a peak of 13.6 U/L. After 20 months, the median FSH level had returned to the normal range. CONCLUSIONS: One adjuvant course of carboplatin was associated with low myelotoxicity and low gonadal toxicity; however, the recurrence rate was almost 9% and thus unsatisfactory. After two courses of carboplatin, no relapse was observed. Thus, the two-course regimen of carboplatin appears to be equivalent to radiotherapy, and because of its favorable toxicity profile, this regimen should be investigated in randomized trials.
Adult↗
Carcinoma in situ in the testis.
Carcinoma in situ (CIS) of the testis is a common precursor of germ-cell tumours in adults and adolescents, with the exception of spermatocytic seminoma. This article reviews existing knowledge on the pathobiology, genetic aspects and epidemiology of CIS, discusses current hypotheses concerning pathogenesis and invasive progression of germ-cell neoplasms and provides guidelines for diagnosis and clinical management of CIS.
Adolescent↗
Second malignancies following pure seminoma.
PURPOSE: Second malignancies in patients with pure testicular seminoma were studied in order to look for adverse late effects of treatment and to study the significance of second malignancies during follow-up. PATIENTS, METHODS: In a multicentric investigation, 839 consecutive patients with pure testicular seminoma were observed for a median follow-up of 3.9 years. Thirty-seven patients had been excluded from the study because they already had had either a contralateral testicular germ cell tumor or another malignancy. 758 patients received radiotherapy, 76 underwent chemotherapy, 5 had surveillance only. The expected rate of second cancers was calculated according to the data of the cancer registry of Saarland, Germany. RESULTS: Twenty-two second cancers (13 contralateral testicular tumors, 9 extratesticular malignancies) were recorded. The overall risk of having a second cancer was RR = 4.8 (95% CI 3. 0-7.3). The risk of having a subsequent testicular tumor is RR = 44. 8 (95% Cl 23.9-76.7). 1.1% of the patients developed a nontesticular second tumor. The risk of having a nontesticular second cancer is RR = 2.1 (95% CI 1.0-4.0). A significantly increased risk was observed for renal cell cancer as well (RR = 12.5; 95% Cl: 1.5-45.1). Increased RR without reaching statistical significance were found for rectal cancer (RR = 5.0; 95% Cl: 0.1-27.9) and non-Hodgkin lymphoma (RR = 6.7; 95% CI 0.2-37.1). None of the second cancers were directly located within the radiation field; 5 neoplasms arose at the border of the radiation field. CONCLUSIONS: This study confirmed the increased risk of having a second testicular germ cell cancer. There is also a small but definitely increased overall risk of having a nontesticular second cancer. Treatment-unrelated factors - possibly genetic predisposition - must be considered for a substantial number of these second tumors, since in the present study the follow-up was rather short and most of the second cancers were located outside of the radiation fields. In particular, the association of renal cancer with testicular cancer appears to be a more than chance occurrence. Second cancer is a real hazard following treatment of testicular cancers and should always be considered during follow-up.
Adult↗
Carcinoma in situ of the testis: review of biological and clinical features.
Carcinoma in situ of the testis (CIS) is the uniform precursor of testicular germ-cell tumours. Morphologically, CIS consists of large, intratubular, gonocyte-like cells with large nuclei and abundant glycogen. CIS cells are probably derived from primordial germ cells and are supposed to be present in the testis of a future testis cancer patient at the time of birth. CIS cells appear to spread inside the seminiferous tubules until CIS progresses to invasive cancer. Diagnosis is best achieved by surgical biopsy of the testis and subsequent immunohistological staining of placental alkaline phosphatase (PlAP). This enzyme is present in embryonal germ cells, CIS and seminoma as well as several other types of germ-cell tumour but usually not in normal germ cells. CIS is found in testicular tissue adjacent to testicular germ-cell tumours in about 90% of cases, and it is observed in all clinical groups known to be at risk for testicular cancer: cryptorchidism (2% to 4%), infertility (0% to 1%), ambiguous genitalia (25%) and contralateral testis of patients with testicular cancer (5%). Conversely, CIS is found in less than 1% of the normal male population, and this prevalence corresponds well to the life-time risk of testicular cancer in males. If CIS is left untreated, there is a 50% probability of progressing to frank germ-cell neoplasm within 5 years. Localised low-dose radiotherapy to the testis eradicates CIS and germ cells, while Leydig cells are preserved. The patient can thus be spared orchiectomy and hormone supplementation. Currently, dose-reduction studies are looking for the optimal radiation dose, which is expected to be around 14 to 16 Gy. After chemotherapy, there is a cumulative risk of 42% for recurrence of CIS within 10 years. The concept of CIS offers the chance of very early detection of testicular cancer and organ-preserving early treatment.
Carcinoma in Situ↗
Prognostic factors in seminomas with special respect to HCG: results of a prospective multicenter study. Seminoma Study Group.
OBJECTIVE: In a prospective multicenter trial, it was our intention to elucidate clinical prognostic factors of seminomas with special reference to the importance of human chorionic gonadotropin (HCG) elevations in histologically pure seminomas. METHODS: Together with 96 participating urological departments in Germany, Austria, and Switzerland, we recruited 803 seminoma patients between 1986 and 1991. Out of 726 evaluable cases, 378 had elevated, while 348 had normal HCG values in the cubital vein. Histology was reviewed by two reference pathologists. HCG levels were determined in local laboratories and in a study laboratory. Standard therapy was defined as radiotherapy in stages I (30 Gy) and IIA/B (36 Gy) to the paraaortal and the ispilateral (stage I) and bilateral (stage IIA/B) iliac lymph nodes; higher stages received polychemotherapy and surgery in case of residual tumor masses. Statistics included chi-square tests, linear Cox regression, and log-rank test. RESULTS: The HCG elevation is associated with a larger tumor mass (primary tumor and/or metastases). HCG-positive and HCG-negative seminomas had no different prognostic outcome after standard therapy. The overall relapse rate of 6% and the survival rate of 98% after 36 months (median) indicate an excellent prognosis. The calculation of the relative risk of developing a relapse discovered only stage of the disease and elevation of the lactate dehydrogenase concentration and its prolonged marker decay as independent prognostic factors for seminomas. A more detailed analysis of the prognostic significance of the stage revealed that the high relapse rate in stage IIB seminomas after radiotherapy (24%) is responsible for this result. CONCLUSIONS: We conclude that HCG-positive seminomas do not represent a special entity. Provided standard therapy is applied, HCG has no influence on the prognosis. Patients with stage IIB disease should be treated with chemotherapy because of the demonstrated higher relapse rate outside the retroperitoneum.
Biomarkers, Tumor↗
False-negative biopsies for testicular intraepithelial neoplasia.
PURPOSE: Testicular intraepithelial neoplasia, also called carcinoma in situ of the testis, is diagnosed by conventional surgical biopsy based on the assumption that testicular intraepithelial neoplasia is randomly distributed throughout the testis. We evaluate the frequency of and possible reasons for false-negative biopsies. MATERIALS AND METHODS: Contralateral testicular biopsy was performed in 1,954 consecutive patients with testicular germ cell tumor. Of the patients 1,859 with a negative biopsy for testicular intraepithelial neoplasia were followed for a median of 6 years. Patients with a second testicular tumor despite previous negative biopsy were evaluated clinically and biopsy specimens were reexamined immunohistologically. RESULTS: Despite negative biopsy 5 patients had a second testis tumor. Testicular intraepithelial neoplasia was detected on reexamination in 2 of the specimens, and mechanical damage to the specimen and technical problems with immunohistochemical staining accounted for the diagnostic failures. The proportion of false-negative biopsies was 0.3% (95% confidence intervals [CI] 0.087 to 0.627). The sensitivity of testicular biopsies to detect testicular intraepithelial neoplasia was 0.95 (95% CI 0.887 to 0.984) and the overall accuracy of the biopsy was 0.997 (95% CI 0.994 to 0.999). To our knowledge 14 cases have been previously reported in the literature, including 2 treated with chemotherapy before testicular biopsy. CONCLUSIONS: The overall proportion of false-negative biopsies for testicular intraepithelial neoplasia is as low as 0.3%. The main reason for diagnostic failure is probably the nonrandom distribution of testicular intraepithelial neoplasia within the testis. Previous chemotherapy and rare technical failures, in particular mechanical damage to the biopsy specimen, may also account for diagnostic failures. Surgical biopsy remains the gold standard for the diagnosis of testicular intraepithelial neoplasia.
Adult↗
[Testicular intraepithelial neoplasms (TIN). An indication for radiotherapy?].
BACKGROUND: Testicular intraepithelial neoplasia (TIN), synonymous for carcinoma in situ of the testis, is a rarely observed preinvasive neoplasia located within the germinative epithelium. According to the current knowledge of the biology of TIN, it is the common precursor of all testicular germ cell neoplasms except spermatocytic seminoma. MATERIAL AND METHODS: This report provides a review of histopathology, epidemiology and diagnostic procedures for TIN and discusses the therapeutic options with particular respect to radiooncological aspects. RESULTS: TIN has a 70% rate of progression to invasive cancer within 7 years. Depending on the individual therapeutic setting surgery, chemotherapy and radiotherapy are alternative treatment modalities. In case of TIN in a single testis or bilateral TIN, local radiotherapy is the standard procedure. With 20 Gy recommended as standard dose in Germany, radiotherapy yields safe eradication of TIN. However, some of the patients show significantly reduced synthesis of testicular androgens. With respect to sporadic reports in the literature, total doses well below 20 Gy might be equally efficient to treat TIN safely. Yet, up to date neither the minimum dose for efficient treatment nor the toxicity profile after consecutive chemo-radiotherapy has been established. CONCLUSIONS: The currently recommended standard dose of 20 Gy in Germany is probably in excess of the minimum dose needed for safe eradication of TIN. Thus, new radiooncological strategies should aim at reducing the total dose of treatment in order to minimize late side effects while maintaining the high efficacy of radiotherapy. This topic is under investigation in a multicenter clinical trial.
Antineoplastic Agents↗
The value of the biopsy of the contralateral testis in patients with testicular germ cell cancer: the recent German experience.
PURPOSE: Testicular intraepithelial neoplasia (TIN; so-called carcinoma in situ of the testis), the precursor of testicular germ cell neoplasms can be detected by testicular biopsy many years before the clinical manifestation of the tumour. This study looked at the prevalence of contralateral TIN in patients with testicular germ cell cancer. The purpose was to evaluate this new approach of early detection of testicular cancer and to evaluate the current management strategies. PATIENTS, METHODS: 1954 consecutive patients with unilateral testicular germ cell tumour underwent contralateral biopsy. All specimens were examined immunohistologically with staining for placental alkaline phosphatase. Patients with TIN were usually submitted to low-dose radiotherapy of the testis. A rebiopsy was performed after 3 months. Endocrinological evaluations were done before, during and after treatment. RESULTS: TIN was observed in 4.9% (95% confidence intervals 3.95%-5.91%). Testicular atrophy constitutes a 4.3 fold increased risk of having contralateral TIN. 64% of the cases with TIN were found in clinically normal testes. Patients with TIN were significantly younger than those without (p < 0.017). No case with TIN was found in patients older than 50 years. Three patients developed a second testicular tumour during follow-up despite a negative biopsy. After radiotherapy, all of 23 patients had complete disappearance of TIN in the rebiopsy. After chemotherapy, 3 of 10 patients had persistent TIN histologically. After radiotherapy, 12 of 41 patients required testosterone replacement. CONCLUSION: The prevalence of contralateral TIN accords well with the known prevalence of bilateral testicular tumours. Testicular atrophy is a strong indicator for the presence of TIN but about 60% of TIN-cases occur without atrophy. Local radiotherapy to the testis with 18-20 Gy is efficaceous in eradicating TIN, but it causes significant damage to almost one quarter of these patients. Chemotherapy is an unsafe treatment for TIN. This study shows the feasibility of early detection of testicular cancer in a high-risk population by means of searching for TIN. Although the management of the condition still needs refinement, the TIN-concept offers an avenue for the early detection of testicular cancer and early conservative management.
Biopsy↗
The prevalence of familial testicular cancer: an analysis of two patient populations and a review of the literature.
BACKGROUND: Undescended testes and antecedent testicular tumor are recognized risk factors for testicular germ cell cancer. It has been suggested that a family history of testicular cancer constitutes another major risk indicator. This postulation is mainly based on clinical observations and on very few systematic investigations. In the current study, the authors analyzed the proportion of familial testicular cancer in their study population and estimated the relative risk created by a family history of the disease. METHODS: The proportion of familial testicular cancer was analyzed in a prospective multicentric study involving 1692 patients. The median ages of patients with and without a family history of the disease were compared. In a different patient population consisting of 518 patients and 531 age-matched controls, the frequency of family history was investigated and the relative risk calculated. In addition, a literature survey was performed to look for previous systematic reports on familial testicular cancer. RESULTS: In the prospective study, 18 patients (1.1%; 95% confidence interval, 0.63-1.68%) had a first-degree relative afflicted with testicular cancer. Age at presentation was not significantly different between patients with a family history and those without. In the retrospective series, the proportion of those with a family history was 1.7% (95% confidence interval [CI], 0.80-3.27%). There was a 3.1-fold increased relative risk (95% CI, 0.77-17.95) for first-degree relatives of patients with testicular cancer. Ten previous reports on familial testicular cancer were identified in the literature. Combining the results of those previous reports and the current study led to a weighted mean prevalence of familial testicular cancer of 1.35% (95% CI, 1.12-1.58%). CONCLUSIONS: The current study underscores that susceptibility to testicular germ cell cancer is influenced by genetic factors. A family history of testicular cancer is encountered in about 1.35% of patients. The relative risk for first-degree relatives of patients with the disease is increased by a factor of 3-10.
Adult↗