Timing of androgen deprivation monotherapy and combined treatments in castration-sensitive and castration-resistant prostate cancer: a narrative review.

PURPOSE: Standard androgen deprivation therapy (ADT) can be initiated early at the time of diagnosis in asymptomatic castration-sensitive advanced prostate cancer. This definition has recently been expanded to also include an early combined treatment with standard ADT and new antihormonal drugs. We aimed to present the best available evidence for the timing of initiation of ADT monotherapy and combined treatments in castration-sensitive/-resistant prostate cancer. METHODS: For this narrative review, we searched Cochrane reviews in the Cochrane Library, systematic reviews and randomized controlled trials in MEDLINE, phase III and ongoing trials in ClinicalTrials.gov and screened the reference lists to extract articles of interest. One author screened the references which were finally included after assessing their relevance through discussion with other experts in the field. RESULTS: The identified references were grouped by medication (standard ADT, androgen biosynthesis inhibitor, androgen receptor antagonists or combined therapies) and tumor stage (castration sensitive or resistant). The evidence was narratively summarized and discussed in the context of the current therapeutic landscape. CONCLUSIONS: Early standard ADT can reduce symptoms of disease progression and may extend progression-free and overall survival. The patient should be well informed about the higher rates of treatment-related side effects. Deferring standard ADT might be indicated only for well-informed or unfit patients. Early standard ADT is increasingly combined with new antihormonal drugs in castration-sensitive metastatic prostate cancer to gain additional survival and quality of life benefits. Combined treatment at the time of development of castration-resistant disease is well established.

[Renal transplantation in urinary diversions]. / Nierentransplantation in Harnableitungen.

Renal transplantations in augmented bladders or urinary diversions are rare, accounting for only 1-2% of all renal transplantations. In most cases a dysfunctional lower urinary tract is the cause of end-stage renal disease in these patients; therefore recovery of the lower urinary tract is mandatory for long-term graft survival. Usually, urinary diversion is timed several months prior to renal transplantation. Beside renal transplantations into an ileum conduit, renal transplantations in continent urinary diversions have become increasingly popular. The most frequent complications are bacteriuria and urinary tract infections, which usually do not lead to graft loss when treated correctly with antibiotics. Long-term outcome of renal transplantations in urinary diversions is comparable to transplantations in healthy native bladders.

[Side effect management of tyrosine kinase inhibitors in urology : Hypertension]. / Nebenwirkungsmanagement von Tyrosinkinaseinhibitoren in der Urologie : Arterielle Hypertonie.

Tyrosine kinase inhibitors like sunitinib, sorafenib, pazopanib or axintinib are regarded the standard of care in the systemic therapy of metastatic renal cell carcinoma. However, the many side effects associated with this therapy pose challenges for the treating physician and the patient. This review offers an overview of the classification and the treatment of hypertension, which is one of the major side effects induced by all tyrosine kinase inhibitors, in order to improve treatment efficacy and patient compliance.

[Side effect management of tyrosine kinase inhibitors in urology : Gastrointestinal side effects]. / Nebenwirkungsmanagement von Tyrosinkinaseinhibitoren in der Urologie : Gastrointestinale Nebenwirkungen.

For approximately one decade, tyrosinkinase inhibitors (TKIs, smart drugs) have dramatically changed and improved the treatment of patients suffering from metastasized renal cell carcinoma. However, the different drugs have substantial side effects. Especially gastrointestinal symptoms may be problematic for patients. These side effects represent a challenge for the physician. On the one hand, dosage modifications and treatment interruption should be avoided to minimize the risk for progression. On the other hand, only mild side effects are tolerable for the patient. Based on a literature review, a clear overview of the incidence of possible side effects for the drugs axitinib, cabozantinib, pazopanib, sorafenib, and sunitinib is provided. Furthermore, we give a practical guide on how to prevent and treat the different gastrointestinal side effects. Finally, it is pointed out when dosage modifications or interruption of treatment are necessary and how to expeditiously re-escalate the treatment after mitigation of side effects.

[Side effect management of tyrosine kinase inhibitors in urology : Fatigue and hypothyroidism]. / Nebenwirkungsmanagement von Tyrosinkinaseinhibitoren in der Urologie : Fatigue und Hypothyreose.

Not only has the use of tyrosine kinase inhibitors (TKI) for the treatment of metastatic renal cell carcinomas (mRCC) changed the therapeutic options for this disease significantly, but with the occurrence of typical side effects this therapy also poses a challenge for the treating physician. Fatigue und hypothyroidism are two common side effects of TKI therapy that can often appear simultaneously. By reducing the patients' quality of life these side effects often lead to a discontinuation of therapy. With this review we want to give the treating physician an overview of the classification and the specific treatment of TKI-induced fatigue and hypothyroidism in order to maximize patients' compliance and the therapeutic efficacy of TKI therapy.

[Perinatal outcome in older primiparas]. / Perinatalni ishod u starih prvorotkinja.

Pregnancy, delivery and the newborn infant of 212 old primiparas (aged greater than or equal to 35 years) and of 1968 age-matched old multiparas as controls were studied for the 1970-1989 period. The frequency of old primiparas and old multiparas was 0.9% and 4.1%, respectively, with no change for the 1970-1979 (1.0%) and 1980-1989 (0.8%) periods. The mean age in the old primiparous and old multiparous groups was 38.08 + 4.2 and 38.2 + 4.8 years, respectively (P greater than 0.05). The old primiparas had an average of 7.37 +/- 2.8 antenatal visits, whereas the old multiparas had 6.08 +/- 3.3 visits (P less than 0.05). The old primiparous group included more employees and fewer unskilled workers and housewives (P less than 0.05), more urban and unmarried pregnant women (P less than 0.001), whereas the old multiparas had more spontaneous and induced abortions (P less than 0.05). Threatened abortion (23.7%), EPH gestosis (20.3%), meconium-stained amniotic fluid (21.7%), caesarean section (35.8%), placental lysis or uterine exploration (6.6%) and episiotomy (100.0%) are more frequent in old primiparas than in old multiparas (P less than 0.05). The duration of labour in old primiparas tends to be longer: there was a significantly smaller number of pregnant women with an up 6-hour duration of labour (42.5%; P less than 0.05). The average duration of labour in the old primiparous and old multiparous groups was 8.18 +/- 5.40 and 5.89 +/- 3.80 hours, respectively (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

[Intrauterine growth of live-born twins in the area of Sibenik, Split and Zadar]. / Intrauterini rast zivorodenih blizanaca na podrucju Sibenika, Splita i Zadra.

By a retrospective analysis the authors studied live-born twins by gestation weeks and birth weight and height: there were 1,195 first-born and 1,189 second-born twins, all from three neighbouring Dalmatian towns (Split, Sibenik and Zadar). A common curve was worked out of the intrauterine growth of both the first and the second twins and a separate curve of each of them. The curves have shown that the twins' birth weight was increassing up to the 40th week of pregnancy; in the 41st week the curve already went down. The authors conclude that twin pregnancy should not last more than 40 weeks.

[Pregnancy and labor in women over 40 years of age]. / Trudnoca i porodaj u rodilja s 40 i vise godina.

During the 1970-1989 period, there were 23,915 deliveries of which 278 (1.16%) occurred in women 40 years of age or older. The latter included 62 (22.3%) primiparas, 158 (56.8%) pluriparas and 58 (20.9%) multiparas. The control group consisted of 14,400 women 20-34 years of age (50% primiparas and 50% pluriparas) from the same period. There was no antenatal visit in 9.4% of the women 40 years of age or older. This group included more housewives, more unmarried women and more women with previous spontaneous and induced abortions than the control group (P less than 0.05). Threatened abortion (16.2%), EPH gestosis (22.3%), impaired glucose tolerance (8.3%), gestational diabetes (7.2%), delivery before 37 weeks (11.5%), delivery after 42 weeks (3.6%), premature rupture of the membranes (18.3%), meconium-stained amniotic fluid (19.8%), elective caesarean section (11.5%), caesarean section delivery (16.5%), vacuum extraction (4.7%), placental lysis or uterine exploration (4.3%) were more frequent in the study than in the control group (P less than 0.05). There were more cases with episiotomy (P less than 0.001) in the control group, whereas there were no differences as regards cervical cerclage, weight gain above 14kg, breech presentation, transverse presentation and assisted breech delivery between the two groups (P greater than 0.05). There was no case of uterine rupture or maternal death either in the study or the control group. The authors conclude that a woman 40 years of age and older is in an advanced age for pregnancy and delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

[Pregnancy, labor and the neonate in multiparas under 34 years of age]. / Trudnoca, porodjaj i novoredjence multipara do 34. godine zivota.

The authors describe the pregnancy, labour and baby in 63 multiparae (five or more births), aged up to 34 years. The control group was composed of 6,480 pregnant patients (2-4 births), aged up to 34 years. The pregnancy in 17.5% of multiparae developed without medical examination and 19.0% of patients had one or two medical control examinations. This finding exceeded the findings in the control group (p less than 0.001). Rural house-wives predominated (p less than 0.001). During labour meconic foetal fluid was found in multiparae. Also exploration of the uterus or desquamation of the placenta were more frequent in them (p less than 0.05). However, the other course of pregnancy was the same as that in the control group (p greater than 0.05). There was no difference in babies born by a multipara or by a mother in the control group (p greater than 0.05). No death was recorded in the two groups. The authors conclude that there was no difference in pregnancy, labour and baby in a multipara with five or more labours and in a pluripara (2-4 births) aged up to 34 years.

[Pregnancy, labor and the neonate in pluriparas and multiparas]. / Trudnoca, porodaj i novorodence pluripare i multipare.

From 1971 to 1988, out of 22001 deliveries (multiple pregnancies excluded) 212 (0.96%) occurred in multiparas with five or more deliveries. The control group included 7340 pluriparas (two to four deliveries) from the same period. In 82.1% cases the multiparas were para 5 and 6, and 63 (29.7%) were less than 34 years of age. 15.9% had no antenatal visit; for the most part they were housewives and rural pregnant women. Transverse presentation, preterm delivery, meconium-stained amniotic fluid, and placental lysis or uterine exploration were more frequent in the multiparous group (P less than 0.001), whereas cervical cerclage and episiotomy were more frequent in the control group (P less than 0.05). Newborn infants in the multiparous group were severely asphyxiated at birth more frequently than those in the control group (P less than 0.05). There were no differences as regards late fetal and early neonatal deaths between the two study groups. The overall perinatal death rate in the multiparas and pluriparas was 2.83% and 1.81%, respectively (P less than 0.05). There was no case of uterine rupture or maternal death in the multiparous and pluriparous group.

Fetal macrosomia--pregnancy and delivery.

The authors have studied pregnancy, delivery and early neonatal status of macrosomic infants (> or = 4000 g) delivered between January 1, 1984, and December 31, 1992. The control group comprised age--and parity--matched pregnant women and their newborns weighing 3000 to 3999 g. From 9980 singleton pregnancies, 2021 (20.3%) macrosomics were delivered. The incidence of macrosomia was 16.7% in the primiparous group, 23.1% in the parity 2-4 group, and 28.2% in the multiparous group (parity > or = 5) (P < 0.001). The rates of macrosomic infants for pregnant adolescents (aged < or = 19 years), pregnant women aged 20-34 years and old pregnant women (> or = 35 years) were 12.0%, 20.6% and 21.5%, respectively (P < 0.001). Macrosomia was not influenced by occupation and antenatal visits (P > 0.05). The rates of > or = 16 kg weight gain in the macrosomic and control groups were 36.2% (mean 14.30 +/- 4.66 kg) and 16.7% (mean 12.18 +/- 4.82 kg), respectively (t = 12.05; P < 0.001). Of 546 pregnant women with fetal macrosomia subjected to oral GT testing, glucose intolerance was found in 20.0% and gestational diabetes in 4.8%. The rates of glucose intolerance and gestational diabetes in 259 control subjects were 13.9% and 2.3%, respectively (P < 0.05). Light (index 1-4) and moderate (index 5-7) forms of EPH gestosis were more common in the macrosomic group, whereas no difference was observed for severe forms (index > or = 8) between the groups (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)