[Blessing in disguise: a favorable consequence of a resuscitation trauma]. / Onni onnettomuudessa--elvytysvamman hyödyllinen seuraus.

Powerful resuscitation may save the life of a person having cardiac arrest. Resuscitation measures may, however, cause injuries as well. We describe a patient, in whom a perforation of the gastric wall as a complication of resuscitation was detected, and upon imaging of the perforation, renal cell carcinoma was detected as an incidental finding. The resuscitation was successful, and the complication of resuscitation led to early diagnosis and treatment of the cancer.

The FinnProstate Study VII: intermittent versus continuous androgen deprivation in patients with advanced prostate cancer.

PURPOSE: We conducted a randomized trial to compare intermittent and continuous androgen deprivation in patients with advanced prostate cancer. We studied time to progression, overall and prostate cancer specific survival, and time to treatment failure. MATERIALS AND METHODS: Between May 1997 and February 2003, 852 men with locally advanced or metastatic prostate cancer were enrolled to receive androgen deprivation therapy for 24 weeks. Patients in whom prostate specific antigen decreased to less than 10 ng/ml, or by 50% or more if less than 20 ng/ml at baseline, were randomized to intermittent or continuous androgen deprivation. In the intermittent therapy arm androgen deprivation therapy was withdrawn and resumed again for at least 24 weeks based mainly on prostate specific antigen decrease and increase. RESULTS: There were 298 patients who did not meet the randomization criteria. The remaining 554 patients were randomized, with 274 (49.5%) to intermittent androgen deprivation and 280 (50.5%) to the continuous androgen deprivation arm. Median followup was 65.0 months. Of these patients 392 (71%) died, including 186 (68%) in the intermittent androgen deprivation arm and 206 (74%) in the continuous androgen deprivation arm (p=0.12). There were 248 prostate cancer deaths, comprised of 117 (43%) in the intermittent androgen deprivation and 131 (47%) in the continuous androgen deprivation arm (p=0.29). Median times from randomization to progression were 34.5 and 30.2 months in the intermittent androgen deprivation and continuous androgen deprivation arms, respectively. Median times to death (all cause) were 45.2 and 45.7 months, to prostate cancer death 45.2 and 44.3 months, and to treatment failure 29.9 and 30.5 months, respectively. CONCLUSIONS: Intermittent androgen deprivation is a feasible, efficient and safe method to treat advanced prostate cancer compared with continuous androgen deprivation.

[Has time already passed the open radical prostatectomy?]. / Onko avoimen radikaaliprostatektomian aika jo takanapäin?

Besides radiotherapy, open radical prostatectomy is an established therapy for localized prostatic cancer. Continuous improvements have been made to the surgical technique, with constantly improving results. Erection is preserved in approximately half of the operated patients, and the risk of urinary incontinence is about 3%. In recent years, open surgery has become rivalled by less invasive forms of surgery, laparoscopic prostatectomy and, above all, robotic laparoscopic prostatectomy, by producing slight reductions in the length of the hospital stay and in surgical bleeding. Even so, the costs of surgical operations may increase even twofold, especially with robotic laparoscopic prostatectomy.

[The effect of castration on bone in prostate cancer patients]. / Kastraation luustovaikutukset eturauhassyöpäpotilailla.

Surgical or chemical castration is widely used for the treatment of advanced prostate cancer. Common side effects of castration are e.g. sweating, increased body fat, decreased muscle mass, impotency and anemia. Castration increases the risk of osteoporosis and fractures in prostate cancer patients via hormonal effects to the bone. Castrated men should be recommended to increase physical activity. Calcium and vitamin-D supplementation is recommended. The European Association of Urology guidelines for prostate cancer recommend bone mineral density measurements before long-lasting castration therapy. Medical therapy should be considered for patients after low-energy fractures, after the diagnosis of osteoporosis based on bone mineral density measurements and for fracture high-risk patients based on clinical decision.

Viability of bovine embryos following exposure to the green filtered or wider bandwidth light during in vitro embryo production.

BACKGROUND: Microscopic light during in vitro production (IVP) is a common stress factor compromising embryo development and viability. Many studies discussing detrimental effects of light have been conducted on in vivo matured/fertilized oocytes or on flushed embryos that were exposed to light only when cultured in vitro. The aim of this work was to examine the effects of light composition during all IVP steps on subsequent embryo development and quality. METHODS: We compared the effects of a green pass filter of 498-563 nm wavelength, and a wider bandwidth of stereomicroscopic light on bovine embryo development rates, total cell counts and the presence of constitutive (Hsp73) and stress-inducible (Hsp72) forms of the Hsp70 protein. RESULTS: The use of the green filter had no effect on embryo development rates, morphological quality or total cell counts on Day 7 or 8 of development compared with control group. However, Hsp72/73 protein levels revealed the protective effect of the filter against harmful blue and infrared regions of the light. The constitutive form Hsp73 was seen in both groups, but the inducible stress-response form Hsp72 was absent from the filter group embryos and appeared only in the group exposed to the stereomicroscopic light. CONCLUSIONS: An easy to use and inexpensive green filter seems to reduce the stress caused by light during the IVP procedures without affecting either the accuracy of embryo monitoring or the need to increase the light intensity.

Finnish multicenter study comparing intermittent to continuous androgen deprivation for advanced prostate cancer: interim analysis of prognostic markers affecting initial response to androgen deprivation.

PURPOSE: Intermittent androgen deprivation has been proposed to prolong hormone sensitivity and improve quality of life in patients with advanced prostate cancer. The FinnProstate Study VII has been performed to identify patients who might benefit from intermittent androgen deprivation. In this interim analysis we evaluated which prognostic markers affect the initial response to androgen deprivation therapy. MATERIALS AND METHODS: A total of 856 men with locally advanced or metastatic prostate cancer were enrolled and given androgen deprivation therapy for 24 weeks to ensure hormone sensitivity. Patients with hormone sensitive prostate cancer were randomized 1:1 to continuous androgen deprivation or intermittent androgen deprivation. The randomization criteria were prostate specific antigen decrease to less than 10 ng/ml or by more than 50% if less than 20 ng/ml at baseline. RESULTS: There were 292 patients (34%) who did not meet the randomization criteria (group 1). The remaining 564 patients (66%) were randomized to intermittent androgen deprivation or continuous androgen deprivation (group 2). Mean prostate specific antigen (834 vs 151 ng/ml), mean alkaline phosphatase (793 vs 292 IU/l), proportion of T4 tumors (37% vs 24%), poorly differentiated cancers (39% vs 26%), metastatic disease (82% vs 51%) and number of skeletal hot spots in M1 disease (more than 5 hot spots 72% vs 42%) were significantly higher in group 1 than in group 2. CONCLUSIONS: Patients with the most advanced prostate cancer and poorest prognosis do not show adequate biochemical prostate specific antigen response to androgen deprivation therapy but should be assessed for eligibility to receive nonendocrine treatment.

Neoadjuvant Chemotherapy Does Not Increase the Morbidity of Radical Cystectomy: A 10-year Retrospective Nationwide Study.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is underutilized in the treatment of bladder cancer (BC). OBJECTIVE: To investigate the effect of NAC on the risk of surgical complications for radical cystectomy (RC) in a population-based setting. DESIGN, SETTING, AND PARTICIPANTS: All radical cystectomies performed in Finland during 2005-2014 were included in the study. Data were collected retrospectively using a web-based data collection platform. Complications were recorded for 90 d using the Clavien classification. Patients treated with NAC were compared to patients receiving RC alone using three cohorts and approaches: the entire cohort, a neoadjuvant period cohort, and a matched cohort. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: For all three cohorts, odds ratios (ORs) were estimated using simple binary logistic regression. In addition, a multivariable stratified logistic model with propensity score was used. For the matched cohort analysis, both univariate and adjusted analyses were carried out. RESULTS AND LIMITATIONS: During 2005-2014, 1427 RCs were performed in Finland, of which 1385 were included in the analyses. NAC was introduced in 2008, and 231 patients (16%) were assigned to NAC and 214 (15%) received two or more cycles of chemotherapy. Within 90 d, 61% of patients experienced complications and mortality was 4% (1.9% in the NAC group, and 4.4% in the RC-alone group). In simple binary logistic regression, NAC patients had significantly fewer complications, but this was not observed in multivariable or propensity score analyses. In the matched cohort analyses, no differences in complication rates could be observed. None of the analyses demonstrated higher complication rates in the NAC group. CONCLUSIONS: Our retrospective study reports on nationwide use of NAC for BC and demonstrates that NAC does not increase RC morbidity. PATIENT SUMMARY: Chemotherapy given before radical surgery does not increase severe postoperative complications in the treatment of bladder cancer.

Long-term outcome of patients with frequently recurrent non-muscle-invasive bladder carcinoma treated with one perioperative plus four weekly instillations of mitomycin C followed by monthly bacillus Calmette-Guérin (BCG) or alternating BCG and interferon-α2b instillations: prospective randomised FinnBladder-4 study.

BACKGROUND: Recurrent TaT1 non-muscle-invasive bladder cancer (NMIBC) patients should be treated with immediate instillation of chemotherapy after transurethral resection of bladder tumour followed by instillation therapy. OBJECTIVE: To present long-term results of a study exploring the effect of initial mitomycin C (MMC) instillations followed by two types of immunotherapy for patients with frequently recurring NMIBC. DESIGN, SETTING, AND PARTICIPANTS: Between 1992 and 1996, 236 patients with frequently recurring TaT1 grade 1-2 NMIBC were enrolled in the prospective randomised multicentre FinnBladder-4 study. INTERVENTION: One perioperative plus four weekly instillations of MMC followed by monthly bacillus Calmette-Guérin (BCG) or alternating BCG and interferon (IFN)-α2b instillations for up to 1 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary end points were time to first recurrence and time to progression. Secondary end points were disease-specific mortality and overall survival. The principal statistical methods were the proportional subdistribution hazards model and Cox proportional hazards model plus cumulative incidence and Kaplan-Meier analyses. RESULTS AND LIMITATIONS: The median follow-up was 10.3 yr (maximum: 19.8 yr) in the MMC-BCG group and 8.6 yr (maximum: 19.8 yr) in the MMC-BCG/IFN group. The probability of recurrence was significantly lower in the MMC-BCG group than in the MMC-BCG/IFN group (43% vs 78% at 10 yr and 45% vs 80% at 15 yr, respectively; hazard ratio: 2.86; 95% confidence interval, 1.98-4.13; p<0.001). There were no significant differences in the probability of progression, disease-free mortality, or overall survival. CONCLUSIONS: Perioperative plus four weekly MMC instillations followed by monthly BCG, instead of alternating BCG and IFN-α2b instillations, significantly reduce long-term recurrence. PATIENT SUMMARY: We demonstrated in non-muscle-invasive bladder cancer patients with exceptionally frequent recurrences that the risk of long-term recurrence was reduced from 78-80% to 43-45% if one perioperative plus four weekly mitomycin C instillations were followed by monthly bacillus Calmette-Guérin (BCG) instillations for 1 yr instead of alternating instillations of BCG and interferon-α2b. TRIAL REGISTRATION: The registration was not considered necessary at this stage of the follow-up because the study was initiated as early as in 1992 and the last randomisation took place in 1996, before the current requirements concerning study registrations were implemented.

Direct laser writing of synthetic poly(amino acid) hydrogels and poly(ethylene glycol) diacrylates by two-photon polymerization.

The additive manufacturing technique of direct laser writing by two-photon polymerization (2PP-DLW) enables the fabrication of three-dimensional microstructures with superior accuracy and flexibility. When combined with biomimetic hydrogel materials, 2PP-DLW can be used to recreate the microarchitectures of the extracellular matrix. However, there are currently only a limited number of hydrogels applicable for 2PP-DLW. In order to widen the selection of synthetic biodegradable hydrogels, in this work we studied the 2PP-DLW of methacryloylated and acryloylated poly(α-amino acid)s (poly(AA)s). The performance of these materials was compared to widely used poly(ethylene glycol) diacrylates (PEGdas) in terms of polymerization and damage thresholds, voxel size, line width, post-polymerization swelling and deformation. We found that both methacryloylated and acryloylated poly(AA) hydrogels are suitable to 2PP-DLW with a wider processing window than PEGdas. The poly(AA) with the highest degree of acryloylation showed the greatest potential for 3D microfabrication.

Comparison of intermittent and continuous androgen deprivation and quality of life between patients with locally advanced and patients with metastatic prostate cancer: a post hoc analysis of the randomized FinnProstate Study VII.

OBJECTIVE: The aim of the study was to compare intermittent (IAD) and continuous (CAD) androgen deprivation therapy (ADT) between locally advanced (M0) and metastatic (M1) prostate cancer, and the effect of ADT on the quality of life. MATERIAL AND METHODS: In total, 852 men with advanced prostate cancer were enrolled to receive goserelin acetate for 24 weeks. Of these, 554 patients whose prostate-specific antigen (PSA) decreased to less than 10 ng/ml or by at least 50% (<20 ng/ml at baseline) were randomized to IAD or CAD. In the IAD arm, ADT was resumed for at least 24 weeks whenever PSA increased to greater than 20 ng/ml or above baseline. RESULTS: Median follow-up time was 65 months. Median times from randomization to progression, death, prostate cancer death and treatment failure in M0 and M1 patients were 46.8 and 21.4, 57.6 and 40.3, 59.5 and 40.7, and 41.9 and 20.0 months, respectively (p < 0.001). No significant differences emerged between IAD and CAD. ADT showed a beneficial effect on pain, activity limitation and social functioning in M1 patients, and a deleterious effect on physical capacity in M0 patients and on sexual functioning in both groups. IAD offered extra benefit for activity limitation, social functioning and recovery of sexual functioning. CONCLUSIONS: IAD is as efficient as CAD in treatment of locally advanced and metastatic prostate cancer. ADT improves quality of life in M1 patients, with IAD offering extra benefit.

Advanced prostate cancer treated with intermittent or continuous androgen deprivation in the randomised FinnProstate Study VII: quality of life and adverse effects.

BACKGROUND: Intermittent dosing may reduce the adverse events (AEs) of androgen-deprivation therapy (ADT). OBJECTIVE: To compare intermittent androgen deprivation (IAD) and continuous androgen deprivation (CAD) with regard to health-related quality of life (QoL). DESIGN, SETTING, AND PARTICIPANTS: A total of 852 men with advanced prostate cancer (PCa) were enrolled to receive goserelin acetate 3.6 mg every 28 d for 24 wk. A total of 554 patients whose prostate-specific antigen (PSA) decreased to <10 ng/ml or by ≥50% (<20 ng/ml at baseline) were randomised to IAD or CAD. INTERVENTION: In the IAD arm, ADT was resumed for at least 24 wk whenever PSA increased >20 ng/ml or above baseline. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: QoL was monitored with a validated Cleary 30-item questionnaire and analysed by the Mann-Whitney U test, 0.5 standard deviation rule, and repeated measures analysis of variance. AEs and adverse drug reactions (ADRs) were analysed by the chi-square test. RESULTS AND LIMITATIONS: Median follow-up was 65 mo. Significant differences in QoL emerged in activity limitation, physical capacity, and sexual functioning, favouring IAD. No significant differences emerged in the prevalence of AEs: 87 patients in the IAD arm (31.8%) and 95 in the CAD arm (33.9%) had cardiovascular (CV) AEs (p=0.59), with 25 (9.1%) and 29 (10.4%) withdrawn (p=0.62), and 21 (7.7%) and 24 (8.6%) dying because of a CV event (p=0.70), respectively; bone fractures occurred in 19 (6.9%) and 15 (5.4%) patients (p=0.44), respectively. Hot flushes or night sweats were the most common ADRs (47.1% vs 50.4%; p=0.44). Erectile dysfunction (15.7% vs 7.9%; p=0.042) and depressed mood (2.2 vs 0%; p=0.032) were more common in the IAD arm. CONCLUSIONS: IAD showed benefits in the treatment of advanced PCa with respect to QoL. The prevalence of AEs was not significantly lower with IAD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00293670.

Stimulation of human embryonic stem cell-derived cardiomyocytes on thin-film microelectrodes.

We describe successful long-term stimulation of human embryonic stem cell-derived cardiomyocyte clusters on thin-film microelectrode structures in vitro. Interdigitated electrode structures were constructed using plain titanium on glass as the electrode material. Titanium rapidly oxidizes in atmospheric conditions to produce an insulating TiO(χ) layer with high relative permittivity. Capacitive coupling to the incubation medium and to the cells adherent to the electrodes was still efficient, and the dielectric layer prevented electrolysis, allowing a wider window of possible stimulation amplitudes to be used, relative to conducting surfaces. A common hypothesis suggests that to achieve proper differentiation of electroactive cells from the stem cells electrical stimuli are also needed. Spontaneously beating cardiomyocyte clusters were seeded on the glass-electrode surfaces, and we successfully altered and resynchronized a clearly different beat interval. The new pace was reliably maintained for extended periods of several tens of minutes.

Parenteral estrogen versus combined androgen deprivation in the treatment of metastatic prostatic cancer: part 2. Final evaluation of the Scandinavian Prostatic Cancer Group (SPCG) Study No. 5.

OBJECTIVE: To compare parenteral estrogen therapy in the form of high-dose polyestradiol phosphate (PEP; Estradurin) with combined androgen deprivation (CAD) in the treatment of prostate cancer patients with skeletal metastases. The aim of the study was to compare anticancer efficacy and adverse events, especially cardiovascular events. MATERIAL AND METHODS: In total, 910 eligible patients with T0-4, NX, M1, G1-3 prostate cancer with an Eastern Cooperative Oncology Group performance status of 0-2 were randomized to treatment with either PEP 240 mg i.m. twice a month for 2 months and thereafter monthly, or flutamide (Eulexin) 250 mg t.i.d. per os in combination with either triptorelin (Decapeptyl) 3.75 mg i.m. per month or on an optional basis bilateral orchidectomy. RESULTS: At this final evaluation of the trial 855 of the 910 patients were dead. There was no difference between the treatment groups in terms of biochemical or clinical progression-free survival or in overall or disease-specific survival. There was no difference in cardiovascular mortality, but a significant increase in non-fatal cardiovascular events in the PEP arm (p<0.05) predominantly caused by an increase in ischemic heart and heart decompensation events. There were 18 grave skeletal events in the CAD group but none in the PEP group (p=0.001). CONCLUSIONS: PEP has an anticancer efficacy equal to CAD and does not increase cardiovascular mortality in metastasized patients, but carries a significant risk of non-fatal cardiovascular events, which should be balanced against the skeletal complications in the CAD group. It is feasible to use Estradurin in the primary or secondary endocrine treatment of metastasized patients without prominent cardiac risk factors and especially those with osteoporosis.

Electric impedance assisted micropipette aspiration.

Micropipette aspiration is a technique to selectively isolate cells from cell cultures using suction pressure. Cells can selectively be isolated one by one from neighboring cells into the micropipette. This paper presents a novel micropipette aspiration system assisted by an impedance measurement system. Furthermore, a method to reduce the adhesion force at a single cell level for a gentler detachment of the cell from a cultivation surface and surrounding cell connections is proposed.

Factors explaining recurrence in patients undergoing chemoimmunotherapy regimens for frequently recurring superficial bladder carcinoma.

OBJECTIVES: To study the factors determining new recurrences in patients with frequently recurring superficial bladder tumors. METHODS: Of all 205 eligible patients, each received 5 weekly intravesical instillations of mitomycin C (MMC), with the first instillation given perioperatively. This was followed, according to randomization, by BCG instillations alone or by alternating instillations of interferon-alpha and BCG monthly for up to 1 year. Impact of 12 variables on time to first recurrence was retrospectively studied with the Cox multiple hazards regression and Kaplan-Meier analysis. RESULTS: Type of regimen was the most significant factor determining new recurrences, with preceding recurrence rate being the most important prognostic factor. Timing of the first MMC was the third significant predictor in the main multivariate analysis, with more than a two-fold relative risk for a new recurrence if the first MMC instillation was given later than on day 0. CONCLUSION: Preceding recurrence rate, most accurately reflects, in patients with frequently recurring tumors, the inherent risk for new recurrences. This risk can be considerably reduced by use of an effective chemoimmunotherapy regimen, and in addition, by inclusion of an early perioperative chemotherapy instillation in such a regimen.