Augmentation of Transient Donor Cell Chimerism and Alloantigen-Specific Regulation of Lung Transplants in Miniature Swine.

Donor alloantigen infusion induces T cell regulation and transplant tolerance in small animals. Here, we study donor splenocyte infusion in a large animal model of pulmonary transplantation. Major histocompatibility complex-mismatched single lung transplantation was performed in 28 minipigs followed by a 28-day course of methylprednisolone and tacrolimus. Some animals received a perioperative donor or third party splenocyte infusion, with or without low-dose irradiation (IRR) before surgery. Graft survival was significantly prolonged in animals receiving both donor splenocytes and IRR compared with controls with either donor splenocytes or IRR only. In animals with donor splenocytes and IRR, increased donor cell chimerism and CD4(+) CD25(high+) T cell frequencies were detected in peripheral blood associated with decreased interferon-γ production of leukocytes. Secondary third-party kidney transplants more than 2 years after pulmonary transplantation were acutely rejected despite maintained tolerance of the lung allografts. As a cellular control, additional animals received third-party splenocytes or donor splenocyte protein extracts. While animals treated with third-party splenocytes showed significant graft survival prolongation, the subcellular antigen infusion showed no such effect. In conclusion, minipigs conditioned with preoperative IRR and donor, or third-party, splenocyte infusions may develop long-term donor-specific pulmonary allograft survival in the presence of high levels of circulating regulatory T cells.

A new prognostic factor for the survival of patients with renal cell carcinoma developing metastatic spinal cord compression.

BACKGROUND AND PURPOSE: This study aimed to identify a potential association of the number of involved extraspinal organs with the survival of patients with metastatic spinal cord compression (MSCC) from renal cell carcinoma. PATIENTS AND METHODS: Data of 69 patients irradiated for MSCC from renal cell carcinoma were retrospectively evaluated for survival. The prognostic value of the number of involved extraspinal organs and eight additional factors were investigated. These additional factors included age, gender, performance status, number of involved vertebrae, interval from cancer diagnosis to radiotherapy (RT) of MSCC, ambulatory status prior to RT, time developing motor deficits, and the fractionation regimen (30 Gy in 10 fractions vs. higher doses). RESULTS: The 6-month survival rates for involvement of 0, 1, and ≥ 2 extraspinal organs were 93, 57, and 21%, respectively (p < 0.001). In the multivariate analysis, the number of involved extraspinal organs maintained significance (risk ratio 2.65; 95% confidence interval 1.64-4.52; p < 0.001). The interval from cancer diagnosis to RT of MSCC (p = 0.013) and ambulatory status prior to RT (p = 0.002) were also independent predictors of survival. CONCLUSION: The number of involved extraspinal organs is a new prognostic factor of survival in patients with MSCC from renal cell carcinoma and should be considered in future clinical trials.

Breast cancer patients with metastatic spinal cord compression. Number of extraspinal organs involved by metastases influences survival.

BACKGROUND AND PURPOSE: The goal of the present work was to investigate the predictive value of the number of extraspinal organs involved by metastases for the survival of patients with metastatic spinal cord compression (MSCC) from breast cancer. PATIENTS AND METHODS: Data of 145 breast cancer patients who received 10 fractions of 3 Gy of radiotherapy (RT) alone for MSCC were retrospectively analyzed. Seven potential prognostic factors were investigated including age, Eastern Cooperative Oncology Group (ECOG) performance score, number of involved vertebrae, interval from breast cancer diagnosis to RT of MSCC, ambulatory status prior to RT, time to developing motor deficits, and the number of involved extraspinal organs. RESULTS: The 1-year survival rates for involvement of 0, 1, 2, and ≥ 3 extraspinal organs were 86, 73, 36, and 16 % (p < 0.001). In the multivariate analysis, the number of involved extraspinal organs remained significant (risk ratio 2.19; 95 % confidence interval 1.61-3.00; p < 0.001). ECOG performance score (p < 0.001), ambulatory status prior to RT (p = 0.003), and the time to developing motor deficits (p < 0.001) were also significantly associated with survival in the multivariate analysis. CONCLUSION: The number of extraspinal organs involved by metastases is an independent prognostic factor of survival in patients with MSCC from breast cancer.

A validated scoring system to identify long-term survivors after radiotherapy for metastatic spinal cord compression.

PURPOSE: This study aimed to develop and validate a scoring system to identify long-term survivors after conventional radiotherapy (RT) for metastatic spinal cord compression (MSCC). PATIENTS AND METHODS: Data from 1,125 patients who had received long-course RT for MSCC were included in this study. Of these patients, 344 survived for over 12 months and 781 died within a year following RT. Based on differences between the distributions of patient characteristics in the two groups, a scoring system was developed. Scores ranged from 0 to 18 points and 15 points was selected as the cutoff for identifying long-term survivors. Data from the 1,125 long-course RT patients (test group) were compared to data from 773 patients receiving short-course RT (validation group). RESULTS: A score of ≥ 15 points was associated with a 94 % proportion of long-term survivors. The 15-point cutoff resulted in a specificity of 98 % and a positive predictive value of 94 % for identification of long-term surviving patients. The proportions of long-term survivors for each scoring point in the validation group were very similar to those in the test group. CONCLUSION: This new scoring system enabled identification of long-term survivors after RT for MSCC with very high specificity and positive predictive value. The score proved to be valid and reproducible.

HDR brachytherapy: an option for preventing nonmalignant obstruction in patients after lung transplantation.

PURPOSE: Interventional bronchoscopy is the main treatment modality in managing benign airway obstructions following lung transplantation. We analyzed the effect of intraluminal brachytherapy on preventing recurrence of hyperplastic tissue. PATIENTS AND METHODS: From September 2002 to September 2004, a total of 24 intraluminal brachytherapy applications were carried out on 12 lung transplant patients in 15 different locations. A single dose of 3 Gy was calculated at a 5-mm distance from the catheter surface; the target volume included a stenosis plus safety interval of 0.5-1.0 cm. RESULTS: All patients had a mean 10.6 local interventions (Argon plasma coagulation, balloon dilatations, stenting) over 4.4 months before the first application of endobronchial brachytherapy, with a mean amount of 2.4 applications per month. The mean forced expiratory volume in 1 s (FEV1) was 2,219 ml in the 3 months before application of brachytherapy. After endobronchial brachytherapy, all patients experienced improvement in clinical status and respiratory function. The mean level of FEV1 in the 3 months after application was 2,435 ml (p = 0.02), and the number of invasive interventions dropped to a mean rate of 5.2 interventions in the 5.1 months after the first intervention, with an amount of 1 application per month. No treatment-related complications were seen. Four patients were treated twice, 1 patient three times, and 1 patient four times at the same localization. CONCLUSIONS: Recurrent symptomatic benign airway obstruction from hyperplastic tissue in the bronchus after lung transplantation can be successfully treated with intraluminal high-dose-rate brachytherapy with a dose of 3 Gy at a 5-mm distance from the catheter surface and a longitudinal safety margin of 1 cm.

Impact of zoledronic acid on control of metastatic spinal cord compression.

BACKGROUND: Zoledronic acid was demonstrated to reduce the rate of skeletal-related events, a hypernym including various outcomes, in patients with bone metastases. In contrast to other studies, this matched-pair analysis focused solely on the impact of zoledronic acid on metastatic spinal cord compression (MSCC). PATIENTS AND METHODS: Data from 98 patients with MSCC receiving radiotherapy plus zoledronic acid were matched 1:2 to 196 patients receiving radiotherapy alone for ten potential prognostic factors. Both groups were compared for local control of MSCC within the irradiated region, overall control of MSCC (local and distant MSCC control), and survival. RESULTS: The 1-year local control rates were 90% after radiotherapy plus zoledronic acid and 81%, after radiotherapy alone (p = 0.042). The 1-year overall control rates were 87% and 75%, respectively (p = 0.016), and the 1-year survival rates were 60% and 52%, respectively (p = 0.17). Results were significant in the Cox proportional hazards model regarding local control (p = 0.024) and overall control (p = 0.008). CONCLUSION: According to the results of this study, zoledronic acid was associated with improved control of MSCC in irradiated patients.

Postoperative periclavicular radiotherapy in breast cancer patients with 1-3 positive axillary lymph nodes. Outcome and morbidity.

PURPOSE: The goal of this work was to examine the possible influence of periclavicular irradiation on outcome of breast cancer patients with 1-3 positive lymph nodes with special emphasis on late toxicity rates. PATIENTS AND METHODS: Between 1997 and 2000, 235 breast cancer patients (T1-2, 1-3 involved lymph nodes) were treated at our department following breast conservative surgery: 139 patients (59.1%) had one, 62 patients (26.4%) two, and 34 patients (14.5%) three positive lymph nodes. Extracapsular spread (ECS) was described in 72 patients (30.6%). There were 67 patients (28.5%) who received additional radiotherapy to the ipsilateral periclavicular lymph nodes (PCLNI), while 168 patients did not (noPCLNI). Patients were re-examined or contacted by phone with regard to treatment-related late effects. RESULTS: After a median follow-up of 78 months (range 7-107 months), 22 patients (9.4%) developed local, 9 (3.8%) axillary, 4 periclavicular (1.7%), and 41 distant failure (17.4%). The actuarial 8-year locoregional recurrence-free (LRRFS), disease-free (DFS), and overall survival rates (OS) were 83%, 67%, and 74%, respectively. Survival data for the PCLNI vs. noPCLNI group were 72% vs. 89% (p = 0.3), 56% vs. 73% (p = 0.4), and 86% vs. 70% (p = 0.3), respectively. No higher toxicity rates were reported in the PCLNI group compared to the noPCLNI group. CONCLUSION: We could not demonstrate any difference in outcome in breast cancer patients with 1-3 positive axillary lymph node metastases with or without periclavicular lymph node irradiation. In addition, patients with PCLNI did not complain about higher rates of late toxicities. However, patients with ECS, which may predict for locoregional failure, may benefit from adjuvant periclavicular irradiation.

Do elderly patients benefit from surgery in addition to radiotherapy for treatment of metastatic spinal cord compression?

BACKGROUND: Treatment of elderly cancer patients has gained importance. One question regarding the treatment of metastatic spinal cord compression (MSCC) is whether elderly patients benefit from surgery in addition to radiotherapy? In attempting to answer this question, we performed a matched-pair analysis comparing surgery followed by radiotherapy to radiotherapy alone. PATIENTS AND METHODS: Data from 42 elderly (age > 65 years) patients receiving surgery plus radiotherapy (S + RT) were matched to 84 patients (1:2) receiving radiotherapy alone (RT). Groups were matched for ten potential prognostic factors and compared regarding motor function, local control, and survival. Additional matched-pair analyses were performed for the subgroups of patients receiving direct decompressive surgery plus stabilization of involved vertebrae (DDSS, n = 81) and receiving laminectomy (LE, n = 45). RESULTS: Improvement of motor function occurred in 21% after S + RT and 24% after RT (p = 0.39). The 1-year local control rates were 81% and 91% (p = 0.44), while the 1-year survival rates were 46% and 39% (p = 0.71). In the matched-pair analysis of patients receiving DDSS, improvement of motor function occurred in 22% after DDSS + RT and 24% after RT alone (p = 0.92). The 1-year local control rates were 95% and 89% (p = 0.62), and the 1-year survival rates were 54% and 43% (p = 0.30). In the matched-pair analysis of patients receiving LE, improvement of motor function occurred in 20% after LE + RT and 23% after RT alone (p = 0.06). The 1-year local control rates were 50% and 92% (p = 0.33). The 1-year survival rates were 32% and 32% (p = 0.55). CONCLUSION: Elderly patients with MSCC did not benefit from surgery in addition to radiotherapy regarding functional outcome, local control of MSCC, or survival.

Re-irradiation of head and neck cancer-impact of total dose on outcome.

AIM: To evaluate the outcome of re-irradiation and to define favourable pre-treatment characteristics. PATIENTS AND METHODS: seventy-five patients with locally recurrent head and neck cancer were treated with re-irradiation, either postoperatively or as definitive treatment, with and without chemotherapy. Mean time period between first and second series of irradiation was 19 months. Mean overall dose of re-irradiation was 46 Gy. Median follow-up was 8.7 months. RESULTS: Overall survival, loco-regional disease-free survival and metastasis-free survival after two years were 23%, 24% and 77%, respectively. Higher overall doses of re-irradiation gave a statistically significant better outcome with regard to overall survival (p=0.018). CONCLUSION: For patients with locally recurrent head and neck cancer, re-irradiation is a feasible therapeutic option. The total dose at re-irradiation improves overall survival. Therefore, re-irradiation with curative intent should only be applied if a sufficient total dose of ≥46 Gy can be given.

High frequency and allele-specific differences of BRCA1 founder mutations in breast cancer and ovarian cancer patients from Belarus.

Breast cancer and ovarian cancer are common malignancies in Belarus accounting for about 3500 and 800 new cases per year, respectively. For breast cancer, the rates and age of onset appear to vary significantly in regions differentially affected by the Chernobyl accident. We assessed the frequency and distribution of three BRCA1 founder mutations 5382insC, 4153delA and Cys61Gly in two hospital-based series of 1945 unselected breast cancer patients and of 201 unselected ovarian cancer patients from Belarus as well as in 1019 healthy control females from the same population. Any of these mutations were identified in 4.4% of the breast cancer patients, 26.4% of the ovarian cancer patients and 0.5% of the controls. In the breast cancer patients, BRCA1 mutations were strongly associated with earlier age at diagnosis, with oestrogen receptor (ER) negative tumours and with a first-degree family history of breast cancer, although only 35% of the identified BRCA1 mutation carriers had such a family history. There were no marked differences in the regional distribution of BRCA1 mutations, so that the significant differences in age at diagnosis and family history of breast cancer patients from areas afflicted by the Chernobyl accident could not be explained by BRCA1. We next observed a higher impact and a shifted mutational spectrum of BRCA1 in the series of Byelorussian ovarian cancer patients where the three founder mutations accounted for 26.4% (53/201). While the Cys61Gly mutation appeared underrepresented in ovarian cancer as compared with breast cancer cases from the same population (p = 0.01), the 4153delA mutation made a higher contribution to ovarian cancer than to breast cancer (p < 0.01). BRCA1 mutations were significantly enriched among ovarian cancer cases with a first-degree family history of breast or ovarian cancer, whereas the median age at ovarian cancer diagnosis was not different between mutation carriers and non-carriers. Taken together, these results identify three BRCA1 founder mutations as key components of inherited breast and ovarian cancer susceptibility in Belarus and might have implications for cancer prevention, treatment and genetic counselling in this population.

[Requirements and performance profile of the Paediatric Radiation Oncology Working Group (APRO): evaluation of the present situation and description of future developments]. / Anforderungen und Leistungsprofile der Arbeitsgemeinschaft Pädiatrische Radioonkologie (APRO): Eine Bestandsaufnahme und Darstellung zukünftiger Entwicklungen.

BACKGROUND: Radiation therapy is an integral component in the management of childhood malignancies and undergoes a continuous process of optimization within the prospective trials of the GPOH. At present there are approximately 20 active protocols, some specifying radio-oncological study questions, in which about 500 to 600 children annually are given radiotherapy. MATERIALS/METHODS: The Pediatric Radiation Oncology Working Group (APRO) of the German Society for Radiation Oncology (DEGRO) represents the organizational link between GPOH and DEGRO. Their activities range from phrasing guidelines of radio-oncological therapy, through writing a protocol for a prospective study on radiation-induced late effects (RISK--in co-operation with GPOH, 695 patients registered so far) and organizing meetings for information transfer, to implementing radio-oncology within the prospective studies of the GPOH by establishing study chairs for radio-oncology when radio-oncological questions are a primary focus and/or to function as a reference institution for quality assurance. These activities also include individual case consultations outside the study proper. Twice annually the members of the APRO meet for an update on current knowledge and future directions where a representative of the GPOH is invited to contribute special aspects of pediatric oncology. CONCLUSIONS: In the future, modern technology (intensity modulated radiotherapy, proton therapy, inclusion of imaging in treatment planning) will be part of disease management in pediatric oncology. A working group for modern radiotherapy technology was established to enhance this development. Prospective studies of the GPOH with primary or secondary radio-oncological questions require the implementation of corresponding tasks (documentation, monitoring, etc.) in order to meet future demands on clinical trials and to achieve the aims of the protocol. Consequently adequate financial support is indispensable.

[Preoperative radiochemotherapy of advanced resectable cancer of the oral cavity with cisplatin vs paclitaxel/carboplatin. Analysis of two multimodality treatment concepts]. / Präoperative Radio-Chemo-Therapie fortgeschrittener, resektabler Mundhöhlenkarzinome mit Cisplatin vs. Paclitaxel/Carboplatin. Analyse zweier multimodaler Therapiekonzepte.

PURPOSE: The purpose of simultaneous chemoradiotherapy is to increase local tumor control and to decrease the incidence of distant metastases. Platinum-based chemotherapy regimens are widely accepted as standard treatment in advanced head and neck cancer. Due to their remarkable activity as well as radiosensitizing effects, taxanes play in increasing role in multimodality treatment concepts of solid tumors. MATERIAL AND METHODS: Since 1989 a total of 85 patients with advanced squamous cell carcinoma of the oral cavity and oropharynx were recruited to participate in two different prospective clinical trials of preoperative chemoradiation. Both treatment concepts (study A: cisplatin 12.5 mg/m(2) plus radiation 36 Gy vs study B: Taxol 40 mg/m(2)/carboplatin AUC 1.5 plus radiation 40 Gy) were compared and further statistical analysis including descriptive analysis as well as univariate and multivariate analysis was performed. RESULTS: At the time of the analysis a total of 47 patients (55.3%) were alive, 38 patients (44.7%) died from tumor-related causes. The overall survival for both patient groups at 5 years was 45.1% (study A) and 84.9% (study B) and after 10 years 32.4% for study group A. A comparative analysis of both groups revealed a highly significant survival benefit at 4 years for study B (p=0.0015). In various calculation models of the multivariate analysis the regimen containing Taxol/carboplatin (study B) was superior to the cisplatin regimen (study A). CONCLUSION: Based on a retrospective analysis of two different concepts of preoperative chemoradiation and supported by recent data from the literature it is justified to conclude that taxane-based combination regimens are more effective compared to cisplatin-based regimens.

Adjuvant vs. neoadjuvant radiochemotherapy for locally advanced rectal cancer: the German trial CAO/ARO/AIO-94.

AIM: The standard treatment for patients with clinically resectable rectal cancer is surgery. Postoperative radiochemotherapy (RCT) is recommended for advanced disease (pT3/4 or pN+). In recent years, encouraging results of pre-operative radiotherapy have been reported. This prospective randomized phase-III-trial (CAO/ARO/AIO-94) compares the efficacy of neoadjuvant RCT to standard postoperative RCT. We report on the design of the study and first results with regard to toxicity of RCT and postoperative morbidity. PATIENTS AND METHODS: Patients with locally advanced operable rectal cancer (uT3/4 or uN+, Mason CS III/IV) were randomly assigned to pre or postoperative RCT: A total dose of 50.4 Gy (single dose 1.8 Gy) was applied to the tumour and the pelvic lymph nodes. 5-FU (1000 mg/m2/d) was administered concomitantly in the 1th and 5th week of radiation as 120 h-continuous infusion. Four additional cycles of 5-FU-chemotherapy (500 mg/m2/d, i.v.-bolus) were applied. RCT was identical in both arms except for a small-volume boost of 5.4 Gy postoperatively. The time interval between RCT and surgery was 4-6 weeks in both arms. Techniques of surgery were standardized and included total mesorectal excision. Primary endpoints of the study are 5-year survival and local and distant control. Secondary endpoints include the rate of curative (R0) resection and sphincter saving procedures, toxicity of RCT, surgical complications and quality of life. RESULTS: As of July 2002, 805 patients were randomized from 26 participating institutions. Acute toxicity (WHO) of RCT was low, with less than 15% of patients experiencing grade 3 or higher toxicity: The principal toxicity was diarrhea, with 12% in the postoperative RCT-arm and 11% in the pre-operative RCT-arm having grade 3-, and 1% in either arm having grade 4-diarrhea. Erythema, nausea and leukopenia were the next common toxicities, with less than 3% of patients in either arm suffering grade 3 or greater leukopenia or nausea. Postoperative complication rates were similar in both arms, with 12% (postop. RCT) and 12% (pre-op. RCT) of patients, respectively, suffering from anastomotic leakage, 3% (postop. RCT) and 3% (pre-op. RCT) from postoperative bleeding, and 6% (postop. RCT) and 4% (pre-op. RCT) from delayed wound healing. CONCLUSION: The patient accrual to the trial is satisfactory. Neoadjuvant RCT is well tolerated and bears no higher risk for postoperative morbidity.

Positron emission tomography with 11C-acetate and 18F-FDG in prostate cancer patients.

Visualisation of primary prostate cancer, its relapse and its metastases is a clinically relevant problem despite the availability of state-of-the-art methods such as CT, MRI, transrectal ultrasound and fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET). The aim of this study was to evaluate the efficacy of carbon-11 acetate and (18)F-FDG PET in the detection of prostate cancer and its metastases. Twenty-five patients were investigated during the follow-up of primary prostate cancer, suspected relapse or metastatic disease using (11)C-acetate PET; 15 of these patients were additionally investigated using (18)F-FDG PET. Fourteen patients were receiving anti-androgen treatment at the time of the investigation. Lesions were detected in 20/24 (83%) patients using (11)C-acetate PET and in 10/15 (75%) patients using (18)F-FDG PET. Based on the results of both PET scans, one patient was diagnosed with recurrent lung cancer. Median (18)F-FDG uptake exceeded that of (11)C-acetate in distant metastases (SUV =3.2 vs 2.3). However, in local recurrence and in regional lymph node metastases, (11)C-acetate uptake (median SUVs =2.9 and 3.8, respectively) was higher than that of (18)F-FDG (median SUVs =1.0 and 1.1, respectively). A positive correlation was observed between serum PSA level and both (11)C-acetate uptake and (18)F-FDG uptake. (11)C-acetate seems more useful than (18)F-FDG in the detection of local recurrences and regional lymph node metastases. (18)F-FDG, however, appears to be more accurate in visualising distant metastases. There may be a role for combined (11)C-acetate/(18)F-FDG PET in the follow-up of patients with prostate cancer and persisting or increasing PSA.

[Prospective phase II study of neoadjuvant radiochemotherapy in advanced operable carcinoma of the mouth cavity. 3-year outcome]. / Prospektive Phase-II-Studie zur neoadjuvanten Radiochemotherapie fortgeschrittener, operabler Mundhöhlenkarzinome. 3-Jahres-Ergebnisse.

PURPOSE: The purpose of simultaneous chemoradiotherapy is to increase local-regional control and to decrease the incidence of distant metastases. Regimens containing cisplatin/5-FU chemotherapy are widely accepted as standard treatment in advanced head and neck cancer. Most studies reported promising response and survival data, but also severe mucosal toxicity. In recent years the newly developed drug Taxol demonstrated interesting activity in head and neck cancer as a single agent as well as in combination drug regimens. In the present outpatient phase II trial, we investigated the combination of Taxol/carboplatin with 40 Gy radiotherapy in a neoadjuvant setting of operable stage III/IV squamous cell carcinoma of the oral cavity and oropharynx. PATIENTS AND METHODS: Fifty-three patients were enrolled in this trial during the period from May 1998 to October 2000 and received five cycles weekly of Taxol (40 mg/m2) and carboplatin (AUC 1.5) with conventional radiotherapy (40 Gy). Within 3-4 weeks after chemoradiotherapy resection of the primary tumor and the regional neck nodes was performed. RESULTS: Fifty-two patients were evaluable for toxicity and response. Complete response was observed in 31 of 52 patients (CR 60%), and partial remission was seen in 21 of 52 patients (PR 40%). In 30 of 52 patients complete pathologic response (pCR 58%) was documented in the resection specimens. The 1-, 2-, and 3-year overall survival rate was calculated as 84%. CONCLUSION: Our present results demonstrated impressive clinical and pathological response rates of concurrent Taxol/carboplatin and radiotherapy as a preoperative treatment modality in advanced oral and oropharyngeal cancer.

[Spermatocytic seminoma. Report of 2 personal cases and review of the literature]. / Das spermatozytäre Seminom. Bericht über 2 eigene Fälle und eine Literaturübersicht.

The spermatocytic seminoma is a distinct testicular neoplasm with a low tendency to metastasize. Two own cases with the diagnosis of a spermatocytic seminoma are presented. A third patient is described, where the initial diagnosis of a spermatocytic seminoma was retrospectively changed to classical seminoma after developing retroperitoneal relapse during surveillance. A literature review revealed distinct histopathological characteristics and a remarkably good prognosis for spermatocytic seminoma. With only one case of relapse confirmed in the literature, in these patients postoperative treatment can safely be omitted in favor of surveillance. In case of spermatocytic seminoma diagnosis should be confirmed by a second pathologist.