Management of Stage I Seminomatous Testicular Cancer: a Systematic Review

The treatment options available for the management of stage I seminoma consist of either a surveillance strategy or adjuvant therapy after orchidectomy. A systematic review was undertaken to identify the optimal management strategy.The MEDLINE and EMBASE databases, in addition to the American Society of Clinical Oncology Meeting Proceedings, were searched for the period 1981 to May 2007. Studies were eligible for inclusion if they discussed at least one of survival, recurrence, second malignancy, cardiac toxicity, or quality of life for patients with stage I seminoma. A search update was carried out in June 2009. Fifty-four reports satisfied the eligibility criteria, including seven clinical practice guidelines, one systematic review, three randomised controlled trials focused on treatment options, 26 non-randomised studies of treatment options, and 15 non-randomised long-term toxicity studies. The existing data suggest that virtually all patients with stage I testicular seminoma are cured regardless of the post-orchidectomy management. The 5-year survival reported in all the studies identified in this systematic review was over 95%, regardless of the management strategy, including surveillance alone with no adjuvant therapy. In conclusion, to date, the optimal management of stage I seminoma remains to be defined. Surveillance seems to be the preferable option, as this strategy minimises the toxicity that might be associated with adjuvant treatment, while preserving high long-term cure rates. The currently available evidence should be presented to patients in order to select the most appropriate option for the individual.     

Pre-exposure of human squamous carcinoma cells to low-doses of gamma-rays leads to an increased resistance to subsequent low-dose cisplatin treatment.

PURPOSE: To investigate low-dose hypersensitivity to cisplatin and increased resistance at higher doses of cisplatin for the human squamous carcinoma cell line SCC-25 and its cisplatin-resistant derivative SCC-25/CP, and to examine the effects of pre- and post-treatment of SCC-25 cells with low-doses of gamma-rays on their resistance to cisplatin. MATERIALS AND METHODS: SCC-25 and SCC-25/CP cells were treated with various cisplatin concentrations (0.1 to 20 microM for 1 h) and assayed for survival using a conventional colony assay. For SCC-25, various doses of gamma-rays (5 cGy to 2.5 Gy) were given either 10 or 60 min before the cisplatin challenge dose as well as either 10 or 60 min after the cisplatin challenge dose. RESULTS: Low-dose (0.5, 0.75 and 1 microM for 1 h) hypersensitivity to cisplatin and increased resistance at higher doses was detected for the SCC-25 cell line, but not for its cisplatin-resistant derivative, SCC-25/CP. Pretreatment of SCC-25 cells with an acute low-dose of 5, 25 cGy or 1 Gy gamma-rays given 60 min before a low-dose cisplatin challenge (0.1 and 1 microM for 1 h) resulted in a significant increase in resistance (p=0.2, 0.01 and <0.001 respectively). For pretreatment of SCC-25 cells with similar low-doses of gamma-rays 10 min before the challenge cisplatin dose, the increased resistance was reduced or absent and was only significantly increased for pretreatment with 25 cGy and a challenge cisplatin dose of 0.1 microM for 1 h (p = 0.02). Similar acute low-doses of y-rays given either 10 or 60 min after the challenge cisplatin dose did not increase resistance. CONCLUSIONS: The human squamous carcinoma cell line SCC-25 showed a low-dose hypersensitivity to cisplatin followed by increased resistance at higher doses. Treatment of SCC-25 cells with low-doses of gamma-rays can induce a protective effect to a subsequent low-dose cisplatin challenge.     

The effect of number of loci on geographical structuring and forensic applicability of Y-STR data in Finland

The Y-chromosomal diversity among Finnish males is characterized by low diversity and substantial geographical substructuring. In a 12-locus data set (PowerPlexY), espe-cially the eastern parts of the country showed low levels of variation, and the western, middle, and eastern parts of Finland differed from each other by their Y-short tandem repeat (STR) haplotype frequencies (Palo et al., Forensic Sci Int Genet 1:120–124, 2007). In this paper, we have analyzed geographical patterns of Y-STR diversity using both 12-locus (PowerPlexY) and 17-locus (Yfiler) data sets from the same set of geographically structured samples. In the larger data set, the haplotype diversity is significantly higher, as expected. The geographical distribution of haplotypes is similar in both data sets, but the level of interregional differences is significantly lower in the Yfiler data. The implications of these observations on the forensic casework are discussed.     

Combined gamma‐irradiation and subsequent cisplatin treatment in human squamous carcinoma cell lines sensitive and resistant to cisplatin

Purpose: To investigate the effects of combined radiation and subsequent cisplatin treatment on the human squamous carcinoma cell line SCC‐25 and its cisplatin‐resistant derivative SCC‐25/CP.

Materials and methods: SCC‐25 and SCC‐25/CP cells were treated with various gamma‐ray doses (5?cGy–7?Gy) followed 60?min later by cisplatin treatment and subsequently assayed for survival using a conventional colony assay. For SCC‐25, the subsequent cisplatin treatment was 0.1, 1, 10 and 20?µM for 1?h. For the more cisplatin‐resistant SCC‐25/CP cells, the subsequent cisplatin treatment was 10 and 50?µM for 1?h.

Results: The cisplatin‐resistant SCC‐25/CP cells were not cross‐resistant to gamma‐irradiation. Subsequent treatment with an LD₅₀ concentration of cisplatin (10 and 50?µM for SCC‐25 and SCC‐25/CP, respectively) resulted in radiosensitization for SCC‐25/CP but not for SCC‐25 cells. Gamma‐irradiation of SCC‐25/CP cells followed by treatment with 10 and 50?µM cisplatin for 1?h resulted in radiation survival curves displaying a significant low‐dose hypersensitive region followed by increased radioresistance at higher doses. A total of 10?µM cisplatin resulted in radiosensitization confined to the low‐dose region (0.05 and 0.25?Gy), whereas the higher cisplatin treatment of 50?µM resulted in the appearance of a hypersensitive region together with a reduction of the increased radioresistance region. In contrast, cisplatin treatment (0.1, 1, 10 and 20?µM for 1?h) of SCC‐25 cells had no significant effect on survival following 2.5 or 7.0?Gy and actually resulted in an increased low‐dose radiation survival (0.05, 0.25 and 1?Gy) when survival was corrected for cisplatin treatment (p<0.01 for all cisplatin concentrations tested).

Conclusions: The significant radiosensitization for SCC‐25/CP given subsequent treatment with 50?µM cisplatin indicates cisplatin can inhibit the increased radioresistance response in SCC‐25/CP cells. In contrast, the subsequent cisplatin treatment of SCC‐25 cells can enhance their survival following low radiation doses.     

Serum amyloid A protein (SAA) subtypes in acute and chronic inflammatory conditions.

Serum amyloid A (SAA), a polymorphic high density lipoprotein associated plasma protein, is the putative circulating precursor of tissue AA protein fibrils in reactive (secondary) amyloidosis. In the present study we examined the SAA subtype pattern in various acute and chronic inflammatory states in order to find out whether disease-specific SAA isoform profiles exist. The method used to study the subtype pattern is based on electrofocusing of serum followed by immunoblotting. Our results show that the SAA subtype pattern is similar in patients with rheumatoid arthritis with or without amyloid. In addition, in amyloidotic subjects the SAA subtype response to acute tissue injury (arthroplasty) did not differ from that in patients without amyloidosis. Analysis of patients with acute and chronic infectious diseases and non-rheumatic inflammatory conditions showed similar SAA patterns in all subjects. These results suggest that the SAA subtype response to tissue injury and inflammation is similar irrespective of the initiating stimulus.     

Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node-negative breast cancer

BACKGROUND: Breast irradiation after lumpectomy is an integral component of breast-conserving therapy that reduces the local recurrence of breast cancer. Because an optimal fractionation schedule (radiation dose given in a specified number of fractions or treatment sessions over a defined time) for breast irradiation has not been uniformly accepted, we examined whether a 22-day fractionation schedule was as effective as the more traditional 35-day schedule in reducing recurrence. METHODS: Women with invasive breast cancer who were treated by lumpectomy and had pathologically clear resection margins and negative axillary lymph nodes were randomly assigned to receive whole breast irradiation of 42.5 Gy in 16 fractions over 22 days (short arm) or whole breast irradiation of 50 Gy in 25 fractions over 35 days (long arm). The primary outcome was local recurrence of invasive breast cancer in the treated breast. Secondary outcomes included cosmetic outcome, assessed with the European Organisation for Research and Treatment of Cancer (EORTC) Cosmetic Rating System. All statistical tests were two-sided. RESULTS: From April 1993 through September 1996, 1234 women were randomly assigned to treatment, 622 to the short arm and 612 to the long arm. Median follow-up was 69 months. Five-year local recurrence-free survival was 97.2% in the short arm and 96.8% in the long arm (absolute difference = 0.4%, 95% confidence interval [CI] = -1.5% to 2.4%). No difference in disease-free or overall survival rates was detected between study arms. The percentage of patients with an excellent or good global cosmetic outcome at 3 years was 76.8% in the short arm and 77.0% in the long arm; the corresponding data at 5 years were 76.8% and 77.4%, respectively (absolute difference = -0.6%, 95% CI = -6.5% to 5.5%). CONCLUSION: The more convenient 22-day fractionation schedule appears to be an acceptable alternative to the 35-day schedule.