Characteristics of the case mix, organisation and delivery in cancer palliative care: a challenge for good-quality research.

OBJECTIVES: Palliative care (PC) services and patients differ across countries. Data on PC delivery paired with medical and self-reported data are seldom reported. Aims were to describe (1) PC organisation and services in participating centres and (2) characteristics of patients in PC programmes. METHODS: This was an international prospective multicentre study with a single web-based survey on PC organisation, services and academics and patients' self-reported symptoms collected at baseline and monthly thereafter, with concurrent registrations of medical data by healthcare providers. Participants were patients ≥18 enrolled in a PC programme. RESULTS: 30 centres in 12 countries participated; 24 hospitals, 4 hospices, 1 nursing home, 1 home-care service. 22 centres (73%) had PC in-house teams and inpatient and outpatient services. 20 centres (67%) had integral chemotherapy/radiotherapy services, and most (28/30) had access to general medical or oncology inpatient units. Physicians or nurses were present 24 hours/7 days in 50% and 60% of centres, respectively. 50 centres (50%) had professorships, and 12 centres (40%) had full-time/part-time research staff. Data were available on 1698 patients: 50% females; median age 66 (range 21-97); median Karnofsky score 70 (10-100); 1409 patients (83%) had metastatic/disseminated disease; tiredness and pain in the past 24 hours were most prominent. During follow-up, 1060 patients (62%) died; 450 (44%) <3 months from inclusion and 701 (68%) within 6 months. ANOVA and χ2 tests showed that hospice/nursing home patients were significantly older, had poorer performance status and had shorter survival compared with hospital-patients (p<.0.001). CONCLUSIONS: There is a wide variation in PC services and patients across Europe. Detailed characterisation is the first step in improving PC services and research. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01362816.

Prescriptions of analgesics during complete disease trajectories in patients who are diagnosed with and die from cancer within the five-year period 2005-2009.

BACKGROUND: Even though validation studies of the WHO analgesic ladder have indicated that the simple approach of the analgesic ladder can provide adequate pain control in most patients, prevalence studies have documented a high prevalence of pain in cancer patients. Little is known about how analgesics are actually prescribed for cancer pain. The aim of the study was to study prescriptions of analgesics during the entire disease trajectory in patients dying from cancer within five years of diagnosis. METHODS: Complete national data from the Norwegian Cancer Registry, the Norwegian Prescription Database, the Cause of Death Registry and Statistics Norway were used to study prescriptions of analgesics in a complete study population of all patients dying from cancer within five years of diagnosis in Norway from 2005 to 2009. RESULTS: Of a total of 10,977 subjects who received prescriptions for analgesics between diagnosis and death, 56% started analgesic treatment at step I of the analgesic ladder, 29% started at step II and 14% started at step III. Of the patients starting at step I, 28% continued to step II, 37% bypassed step II and moved directly to step III whereas the remaining 35% remained at step I. Approximately 60% received one or more dispensed prescription of a step III analgesic during the disease trajectory, whereas nearly 20% remained at step I and 20% at step II respectively. CONCLUSION: The study indicates that clinicians seem to individually tailor analgesic treatment instead of applying the stepwise approach in the WHO analgesic ladder. SIGNIFICANCE: Complete national data covering the complete disease trajectory in cancer patients dying within five years of diagnosis. The majority of patients do not receive treatment in concordance with the stepwise approach suggested by the WHO analgesic ladder.

A randomized phase III study comparing standard dose BEP with sequential high-dose cisplatin, etoposide, and ifosfamide (VIP) plus stem-cell support in males with poor-prognosis germ-cell cancer. An intergroup study of EORTC, GTCSG, and Grupo Germinal (EORTC 30974).

BACKGROUND: To compare the efficacy of one cycle of standard dose cisplatin, etoposide, and ifosfamide (VIP) plus three cycles of high-dose VIP followed by stem-cell infusion [high-dose chemotherapy (HD-CT arm)] to four cycles of standard cisplatin, etoposide, and bleomycin (BEP) in patients with poor-prognosis germ-cell cancer (GCC). PATIENT AND METHODS: Patients with poor-prognosis GCC were assigned to receive either BEP or VIP followed by HD-CT. To show a 15% improvement in a 1-year failure-free survival (FFS), the study aimed to recruit 222 patients but closed with 137, due to slow accrual. RESULTS: One hundred thirty-one patients were included in this analysis. The complete response rates in the HD-CT and in the BEP arm did not differ: (intention to treat) 44.6% versus 33.3% (P = 0.18). There was no difference in FFS between the two treatment arms (P = 0.057, 66 events). At 2 years, the FFS rate was 44.8% [95% confidence interval (CI) 32.5-56.4] and 58.2%, respectively (95% CI 48.0-71.9); but this 16.3% (standard deviation 7.5%) difference was not statistically significant (P = 0.060). Overall survival did not differ between the two groups (log-rank P > 0.1, 47 deaths). CONCLUSION: This study could not demonstrate that high-dose chemotherapy given as part of first-line therapy improves outcome in patients with poor-prognosis GCC.

Classification of pain in cancer patients--a systematic literature review.

One of the aims of the European Palliative Care Research Collaborative (EPCRC) is to achieve consensus on a classification system for cancer pain. We performed a systematic literature review to identify existing classification systems and domains/items used to classify cancer patients with pain. In a systematic search in the databases Medline and Embase, covering 1986-2006, 692 hits were obtained. 92 papers were evaluated to address pain classification. Six standardised classification systems were identified; three of them systematically developed and partially validated. Both pain characteristics and patient characteristics relevant for cancer pain classification were included in the classification systems. All but one of the standardised systems aim at predicting treatment response or adequacy of treatment. Several domains and items used to describe cancer pain but not formally described as part of a classification system were also identified and systematized. The existing approaches to pain classification in cancer patients are different, mostly not thoroughly validated, and none is widely applied. An internationally accepted classification system for cancer pain could improve research and cancer pain management. This systematic review suggests a need for developing an international consensus on how to classify pain in cancer patients.

Predicted cardiovascular mortality and reported cardiovascular morbidity in testicular cancer survivors.

INTRODUCTION: We examined if testicular cancer (TC) treatment is associated with any risk for cardiovascular morbidity or predicted mortality according to the SCORE model, in which a 10-year future risk of >or=5% for developing a fatal cardiovascular event qualify for high-risk status. METHODS: One thousand one hundred thirty-four TC survivors treated 1980-1994 participated in this study (1998-2002). Patients were categorised in four treatment groups: surgery (n = 225), radiotherapy (n = 445), and two chemotherapy groups: cumulative cisplatin dose 850 mg (cis>850, n = 89). Patients with cardiovascular disease, diabetes or SCORE >or=5% constituted a high-risk group, and those with SCORE >1% an intermediate/high risk group. RESULTS: Age-adjusted mean SCORE was 0.93% for the surgery group. In comparison, chemotherapy treated patients had significantly higher SCORE (1.07%, p = 0.01). Only 15% of patients were scored to be at high-risk, while 53% qualified for the intermediate/high risk group. Patients in the cis>850 group had increased odds for having intermediate/high risk, compared with the surgery group (OR 3.4, 95% CI 1.3-8.7). Only 23 cardiovascular events had occurred since the testicular cancer diagnosis. CONCLUSION: The SCORE model indicates that patients treated with cisplatin-based chemotherapy have a significantly increased future risk of a fatal cardiovascular event. IMPLICATIONS FOR CANCER SURVIVORS: TC survivors should be followed regularly with respect to cardiovascular risk profile beyond the routine 10-year clinical follow-up.

Components of the metabolic syndrome in long-term survivors of testicular cancer.

BACKGROUND: A possible explanation of the excess cardiovascular risk in testicular cancer (TC) survivors is development of metabolic syndrome. The association between metabolic syndrome and TC treatment is examined in long-term survivors. PATIENTS AND METHODS: In a national follow-up study (1998-2002), 1463 TC survivors (diagnosed 1980-1994) participated. Patients >60 years were excluded in the present study, leaving 1135 patients eligible. The patients were divided in four treatment groups: surgery (n = 225); radiotherapy (n = 446) and two chemotherapy groups: cumulative cisplatin dose (Cis) 850 mg (n = 88). A control group consisted of 1150 men from the Tromsø Population Study. Metabolic syndrome was defined according to a modified National Cholesterol Education Program definition. RESULTS: Both chemotherapy groups had increased odds for metabolic syndrome compared with the surgery group, highest for the Cis >850 group [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.6-4.7]. Also, the Cis >850 group had increased odds (OR 2.1, 95% CI 1.3-3.4) for metabolic syndrome compared with the control group. The association between metabolic syndrome and the Cis >850 group was strengthened after adjusting for testosterone, smoking, physical activity, education and family status. CONCLUSION: TC survivors treated with cisplatin-based chemotherapy have an increased risk of developing metabolic syndrome compared with patients treated with other modalities or with controls.

Blood pressure and body mass index in long-term survivors of testicular cancer.

PURPOSE: To evaluate blood pressure and body mass index (BMI) in long-term survivors of testicular cancer (TC) treated with different modalities. PATIENTS AND METHODS: One thousand eight hundred fourteen patients treated for unilateral TC in Norway (1980 to 1994) were invited to participate in a follow-up study (1998 to 2002), including measurements of systolic blood pressure (SBP), diastolic blood pressure (DBP), and BMI. Of these patients, 1,289 patients (71%) participated in the study. The patients were categorized into four treatment groups: surgery (n = 242), radiotherapy (n = 547), and two chemotherapy groups, cumulative cisplatin dose < or = 850 mg (n = 402) and cumulative cisplatin dose more than 850 mg (n = 98). A control group consisted of healthy males from the Tromsø Population Study (n = 2,847). RESULTS: At diagnosis, age-adjusted regression analyses showed no differences between the treatment groups for any variables. After a median follow-up time of 11.2 years, age-adjusted SBP and DBP were significantly higher for both chemotherapy groups compared with the surgery group. Chemotherapy-treated patients had increased odds for hypertension at follow-up compared with the surgery group, and the odds were highest for the cisplatin more than 850 mg group (odds ratio = 2.4; 95% CI, 1.4 to 4.0). The cisplatin more than 850 mg group had a significantly higher 10-year BMI increase and a higher prevalence of obesity at follow-up than the surgery group. Compared with healthy controls, chemotherapy-treated patients had, at follow-up, increased SBP, increased DBP, excessive BMI increase, and a higher prevalence of hypertension. CONCLUSION: Five to 20 years after therapy, cured TC patients treated with cisplatin-based chemotherapy had significantly higher levels of blood pressure, a higher prevalence of hypertension, and an excessive weight gain compared with patients treated with other modalities and compared with healthy controls.

Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial.

BACKGROUND: Adjuvant radiotherapy is effective treatment for stage I seminoma, but is associated with a risk of late non-germ-cell cancer and cardiovascular events. After good results in initial studies with one injection of carboplatin, we undertook a large randomised trial to compare the approaches of radiotherapy with chemotherapy in seminoma treatment. METHODS: Between 1996 and 2001, 1477 patients from 70 hospitals in 14 countries were randomly assigned to receive radiotherapy (para-aortic strip or dog-leg field; n=904) or one injection of carboplatin (n=573; dose based on the formula 7x[glomerular filtration rate+25] mg), at two trial centres in the UK and Belgium. The primary outcome measure was the relapse-free rate, with the trial powered to exclude absolute differences in 2-year rates of more than 3%. Analysis was by intention to treat and per protocol. This trial has been assigned the International Standard Randomised Controlled Trial Number ISRCTN27163214. FINDINGS: 885 and 560 patients received radiotherapy and carboplatin, respectively. With a median follow-up of 4 years (IQR 3.0-4.9), relapse-free survival rates for radiotherapy and carboplatin were similar (96.7% [95% CI 95.3-97.7] vs 97.7% [96.0-98.6] at 2 years; 95.9% [94.4-97.1] vs 94.8% [92.5-96.4] at 3 years, respectively; hazard ratio 1.28 [90% CI 0.85-1.93], p=0.32). At 2 years' follow-up, the absolute differences in relapse-free rates (radiotherapy-chemotherapy) were -1.0% (90% CI -2.5 to 0.5) by direct comparison of proportions, and 0.9% (-0.5 to 3.0) by a hazard-ratio-based approach. Patients given carboplatin were less lethargic and less likely to take time off work than those given radiotherapy. New, second primary testicular germ-cell tumours were reported in ten patients allocated irradiation (all after para-aortic strip field) and two allocated carboplatin (5-year event rate 1.96% [95% CI 1.0-3.8] vs 0.54% [0.1-2.1], p=0.04). One seminoma-related death occurred after radiotherapy and none after carboplatin. INTERPRETATION: This trial has shown the non-inferiority of carboplatin to radiotherapy in the treatment of stage I seminoma. Although the absence of disease-related deaths and preliminary data indicating fewer second primary testicular germ-cell tumours favour carboplatin use, these findings need to be confirmed beyond 4 years' follow-up.

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.

Somatic mutations of KIT in familial testicular germ cell tumours.

Somatic mutations of the KIT gene have been reported in mast cell diseases and gastrointestinal stromal tumours. Recently, they have also been found in mediastinal and testicular germ cell tumours (TGCTs), particularly in cases with bilateral disease. We screened the KIT coding sequence (except exon 1) for germline mutations in 240 pedigrees with two or more cases of TGCT. No germline mutations were found. Exons 10, 11 and 17 of KIT were examined for somatic mutations in 123 TGCT from 93 multiple-case testicular cancer families. Five somatic mutations were identified; four were missense amino-acid substitutions in exon 17 and one was a 12 bp in-frame deletion in exon 11. Two of seven TGCT from cases with bilateral disease carried KIT mutations compared with three out of 116 unilateral cases (P=0.026). The results indicate that somatic KIT mutations are implicated in the development of a minority of familial as well as sporadic TGCT. They also lend support to the hypothesis that KIT mutations primarily take place during embryogenesis such that primordial germ cells with KIT mutations are distributed to both testes.

Erroneous diagnosis of pancreatic cancer after radiotherapy of testicular cancer.

BACKGROUND: After radiotherapy with or without chemotherapy radiation-induced normal tissue alteration may mimic cancer and may cause major morbidity. RESULTS: Two patients irradiated for seminoma, in one case combined with cisplatin-based chemotherapy, developed clinical symptoms and radiological signs comparable to pancreatic cancer (stenosis of the ductus choledochus). The non-malignant diagnosis was finally established by revision of the histological specimen (case 1) and per-operatively (case 2). In both patients by-pass operations for biliary tract stenosis resulted in excellent palliation. CONCLUSION: Radiation-induced fibrosis within the upper retroperitoneal space is an important differential diagnosis versus pancreatic cancer in patients with prior radiotherapy for seminoma. Diagnosis based only on clinical and radiological findings may lead to incorrect patient information and registration errors in Cancer Registries.

Increased mortality rates in young and middle-aged patients with malignant germ cell tumours.

Cisplatin-based chemotherapy of malignant germ cell tumours (MGCT) has been reported to increase the risk of cardiovascular morbidity. A high incidence of second nongerm cell malignancies is well documented in MGCT survivors. The death risk due to these conditions is, however, more unknown in MGCT patients. Standard mortality rates (SMRs) were established in 3378 Norwegian MGCT patients treated from 1962 to 1997 aged

Testicular carcinoma in situ in patients with extragonadal germ-cell tumours: the clinical role of pretreatment biopsy.

BACKGROUND: The aim of this study was to determine the prevalence of testicular carcinoma in situ (CIS) in patients with a malignant extragonadal germ-cell tumour (EGGCT) and the incidence of metachronous invasive testicular cancer (TC) in relation to the pretreatment demonstration of CIS. PATIENTS AND METHODS: Sixty-eight patients with EGGCT (53 retroperitoneal, 15 mediastinal) had pre-chemotherapy histological assessment of one (13) or both (55) testicle(s). A total of 123 testicles were examined for the presence of CIS. RESULTS: Testicular CIS was found in 21 patients (31%) (18 retroperitoneal EGGCT, three mediastinal EGGCT). Two patients had bilateral CIS. Five patients, four of them with proven pretreatment CIS, developed a metachronous TC. The 10-year invasive-free TC survival rate for all 68 patients was 88%, but only 65% for those with proven pretreatment CIS. The overall 10-year survival rate for all patients was 82%. CIS was demonstrated in seven of 48 trans-scrotal core biopsies, in 10 of 56 trans-scrotal surgical biopsies and in five of 11 orchiectomy specimens. CONCLUSIONS: Approximately one-third of patients with EGGCT present with testicular CIS, predominantly those with a retroperitoneal tumour. These patients have a considerable risk of metachronous TC development in spite of chemotherapy. The pretreatment demonstration of testicular CIS in patients with EGGCT gives the possibility of individualised counselling and safe follow-up, and is therefore highly recommended. The data are in agreement with a multi-site development of malignant germ-cell tumours, but do not exclude the possibility that the retroperitoneal EGGCTs in particular represent metastases from a burned-out TC.

Intensive induction chemotherapy with CBOP/BEP in patients with poor prognosis germ cell tumors.

PURPOSE: Despite a high cure rate in patients with testicular cancer, there remain patients in the poor prognosis group who have a less favorable outcome. Intensive induction chemotherapy using a regimen consisting of carboplatin, bleomycin, vincristine, and cisplatin, followed by bleomycin, etoposide, and cisplatin (CBOP/BEP), developed at the Royal Marsden Hospital, is designed to overcome the rapid proliferation seen in germ cell tumors. This study assesses the outcome of patients with poor-prognosis nonseminomatous germ cell tumors (NSGCT) treated with CBOP/BEP. PATIENTS AND METHODS: Patients with NSGCT from three centers, classified as poor prognosis according to International Germ Cell Classification Consensus Group criteria, were treated with CBOP/BEP regimen during the period from 1989 to 2000. Data on treatment toxicity, relapse-free survival (RFS), and overall survival (OS) were collected prospectively on a hospital database. RESULTS: Fifty-four male patients with poor prognosis NSGCT were treated with CBOP/BEP. The RFS at 3 and 5 years for all patients was 83.2% (95% confidence interval [CI], 68.8% to 91.3%). After a median follow-up of 4 years, the OS of the 54 patients was 91.5% (95% CI, 78.6% to 96.8%) at 3 years and 87.6% (95% CI, 71.3% to 94.9%) at 5 years. Three-year OS in patients with a primary mediastinal germ cell tumor was 77.1% (95% CI, 34.5% to 93.9%) compared with 95.4% (95% CI, 82.8% to 98.8%) in patients with a testicular primary tumor (P =.24). CONCLUSION: The results reported here compare favorably with the historical results of alternative regimens used in the management of poor-prognosis NSGCT. We suggest a phase III trial to confirm our findings.

Long-term renal function after treatment for malignant germ-cell tumours.

OBJECTIVE: To evaluate prospectively renal function in patients with malignant germ-cell tumours (MGCTs) >10 years after retroperitoneal lymph node dissection alone (RPLND), radiotherapy alone (RAD) or different schedules of cisplatin-based chemotherapy with or without surgery/radiotherapy (CHEM). PATIENTS AND METHODS: In 85 patients, three groups were identified: RPLND, 14; RAD, 18; CHEM, 53, with subdivision of the latter group according to the cumulative cisplatin dose or the additional use of radiotherapy. Renal function was determined by 131Iodine Hippuran clearance or 99m DTPA glomerular filtration rate, and was assessed before treatment and four times during 14 years of follow-up. A value of <70% of the upper limit of the normal range identified impaired renal function. RESULTS: Twenty-five patients displayed long-term impaired renal function, 23 of them from the RAD or CHEM group. In the RAD group, renal function decreased by 8%, whereas a 14% reduction of renal function was observed in the CHEM group. In the CHEM group the cumulative dose of cisplatin, and in the RAD group the age at treatment, were associated with impairment of renal function. Combining all patients, age at treatment and the type of treatment were associated with impaired renal function. CONCLUSIONS: In 20-30% of the patients with germ-cell tumour, standard radiotherapy and chemotherapy strategies are followed by long-term subclinical impaired renal function. These findings support current intentions to avoid overtreatment with these treatment modalities.

Anxiety and depression in cancer patients: relation between the Hospital Anxiety and Depression Scale and the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire.

BACKGROUND: The emotional functioning (EF) dimension of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C33) and the Hospital Anxiety and Depression Scale (HADS) evaluate anxiety and depression. We wanted to compare cancer patients' responses to EF with those to HADS, as well as the impact of anxiety and depression on the quality of life (QL) dimensions of the EORTC QLQ C33. METHOD: A total of 568 cancer patients completed both the EORTC QLQ C33 and HADS at the same occasion. The association between the patients' EF scorings and their HADS scores was analyzed by multiple linear regression. Gender and age were included as covariates. RESULTS: Statistically significant negative relations were found between EF and HADS-A (anxiety), HADS-D (depression) and HADS-T (total score), respectively, with the highest correlation coefficient for HADS-A. Older patients and males reported less emotional distress assessed by the EF scale than younger ones and females with comparable HADS-T or HADS-D scores. Both HADS-A and HADS-D were significantly related to other QL dimensions, and depression was a stronger predictor for reduced QL than anxiety. CONCLUSION: The EF dimension of EORTC QLQ C33 predominantly assesses anxiety, whereas depression is rated to a lesser degree. Combined with significant age and gender relations, this implies a risk of underdiagnosed depression, if the EORTC QLQ C33 is used as the only instrument to screen for psychological distress in cancer patients. As depression has a stronger impact on global QL of cancer patients than anxiety, the use of an additional instrument is recommended for assessment of depression.

[Treatment of renal carcinoma with distant metastases]. / Behandling av nyrekreft med fjernmetastaser.

BACKGROUND: There is no effective standard therapy for patients with distant metastases from renal cell carcinoma. Physicians should, however, know about the different treatment options and their efficacy in order to adequately inform and treat their patients. MATERIAL AND METHODS: Current relevant literature and experience at the Norwegian Radium Hospital are reviewed with emphasis on systemic therapy. RESULTS: Nephrectomy is indicated if the aim is to palliate or prevent local symptoms due to a large primary tumour, or if the operation renders a patient eligible for a clinical trial. Local symptoms due to metastatic lesions should be managed surgically or by radiotherapy. Hormone treatment and current chemotherapy are ineffective. In selected patients interferon-alpha (IFN-alpha) results in an approximately 15% response rate and 4-6 months' prolongation of life. Combination therapy with interleukins or with other drugs is experimental. INTERPRETATION: Patients with metastatic renal cell carcinoma should primarily be included in clinical trials. If this is not possible, interferon-alpha monotherapy represents today's standard systemic treatment, to be offered to selected and informed patients.

False-negative biopsy for testicular intraepithelial neoplasia and high-risk features for testicular cancer.

The purpose of this report is to emphasize the possibility of false-negative biopsies for testicular intraepithelial neoplasia (TIN) in men with high-risk features of testicular cancer and to review the relevant literature. At the Norwegian Radium Hospital patients in this category are offered the chance to undergo a testicular biopsy. A patient is described who had a normal testicular biopsy a decade before presenting with an invasive testicular cancer. Furthermore, this patient is the first case reported with a false-negative biopsy for TIN and a family history of testicular cancer. The evaluation of the biopsies included immunohistochemical staining for c-kit and PIAP (placental-like alkaline phosphatase) in order to diagnose early TIN. Though multifocal or diffuse extension seems to be the most frequent pattern of distribution of TIN, the presented case and another 14 cases from the literature review indicate that the focality of TIN may be a reason for a TIN-negative biopsy.

Ejaculation in testicular cancer patients after post-chemotherapy retroperitoneal lymph node dissection.

The purpose of this study was to evaluate fertility after different types of post-chemotherapy retroperitoneal lymph node dissection (RPLND). During 1980-1994, 192 patients with metastatic testicular cancer underwent post-chemotherapy RPLND with a gradual shift from modified bilateral template RPLND to nerve-sparing RPLND. Modified bilateral template RPLND was done in 92% of the patients operated during 1980-1984 as compared to 16% during 1989-1994. Pre- and post-treatment fertility was assessed by microscopic sperm analysis, determination of serum FSH and information on ejaculation and paternity. There was no significant difference of the survival rates between the three treatment periods. Antegrade ejaculation was preserved in 11% of the patients after modified bilateral template RPLND as compared to 89% after the nerve-sparing operation technique. The median ejaculatory volume decreased post-operatively, serum FSH increased and sperm density remained unchanged. Fifty-six patients attempted fatherhood after their treatment, and 27 fathered at least one child after an observation-time of 55 months, nine of them by assisted fertilization. Patients with initially advanced testicular cancer but limited residual retroperitoneal masses after induction chemotherapy can safely undergo limited post-chemotherapy RPLND as a part of multimodality treatment. After nerve-sparing RPLND antegrade ejaculation is preserved in 89% of the patients though the ejaculatory volume decreases after RPLND. Post-treatment fatherhood can be achieved in at least 50% of the patients attempting paternity.