Health-related quality of life after interval cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with stage III ovarian cancer.

INTRODUCTION: The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery (CRS) improves recurrence-free (RFS) and overall survival (OS) in patients with FIGO stage III ovarian cancer. We evaluated the effect of HIPEC on patient's health-related quality of life (HRQoL) in the OVHIPEC trial. MATERIALS AND METHODS: OVHIPEC was a multicentre, open-label, randomized phase III trial for patients with stage III ovarian cancer. Patients were randomly assigned (1:1) to receive interval CRS with or without HIPEC with cisplatin. HRQoL was assessed using the EORTC QLQ-C30, and the ovarian (QLQ-OV28) and colorectal cancer (QLQ-CR38) modules. HRQoL questionnaires were administered at baseline, after surgery, after end of treatment, and every three months thereafter. HRQoL was a secondary endpoint, with the prespecified focus on the QLQ-C30 summary score and symptom scores on fatigue, neuropathy and gastro-intestinal symptoms. HRQoL was analysed using linear and non-linear mixed effect models. RESULTS: In total, 245 patients were randomized. One-hundred-ninety-seven patients (80%) completed at least one questionnaire. No significant difference over time in the QLQ-C30 summary scores was observed between the study arms (p-values for linear and non-linear growth: p > 0.133). The pattern over time for fatigue, neuropathy and gastro-intestinal symptoms did not significantly differ between treatment arms. CONCLUSION: The addition of HIPEC to interval CRS does not negatively impact HRQoL in patients with stage III ovarian cancer who are treated with interval CRS due to the extent of disease. These HRQoL results, together with the improvement in RFS and OS, support the viability of HIPEC as an important treatment option in this patient population. CLINICALTRIALS. GOV NUMBER: NCT00426257. EUDRACT NUMBER: 2006-003466-34.

No influence of sarcopenia on survival of ovarian cancer patients in a prospective validation study.

OBJECTIVE: Decrease in skeletal muscle index (SMI) during neoadjuvant chemotherapy (NACT) has been associated with worse outcome in patients with advanced ovarian cancer. To validate these findings, we tested if a decrease in SMI was a prognostic factor for a homogenous cohort of patients who received NACT in the randomized phase 3 OVHIPEC-trial. METHODS: CT-scans were performed at baseline and after two cycles of neoadjuvant chemotherapy in stage III ovarian cancer patients. The SMI (skeletal muscle area in cm2 divided by body surface area in m2) was calculated using SliceOMatic software. The difference in SMI between both CT-scans (ΔSMI) was calculated. Cox-regression analyses were performed to analyze the independent effect of a difference in SMI (ΔSMI) on outcome. Log-rank tests were performed to plot recurrence-free (RFS) and overall survival (OS). The mean number of adverse events per patient were compared between groups using t-tests. RESULTS: Paired CT-scans were available for 212 out of 245 patients (87%). Thirty-four of 74 patients (58%) in the group with a decrease in ΔSMI and 73 of 138 of the patients (53%) in the group with stable/increase in ΔSMI had died. Median RFS and OS did not differ significantly (p = 0.297 and p = 0.764) between groups. Patients with a decrease in SMI experienced more pre-operative adverse events, and more grade 3-4 adverse events. CONCLUSION: Decreased SMI during neoadjuvant chemotherapy was not associated with worse outcome in patients with stage III ovarian cancer included in the OVHIPEC-trial. However, a strong association between decreasing SMI and adverse events was found.

Sentinel nodes in vulvar cancer: Long-term follow-up of the GROningen INternational Study on Sentinel nodes in Vulvar cancer (GROINSS-V) I.

OBJECTIVE: In 2008 GROINSS-V-I, the largest validation trial on the sentinel node (SN) procedure in vulvar cancer, showed that application of the SN-procedure in patients with early-stage vulvar cancer is safe. The current study aimed to evaluate long-term follow-up of these patients regarding recurrences and survival. METHODS: From 2000 until 2006 GROINSS-V-I included 377 patients with unifocal squamous cell carcinoma of the vulva (T1, <4 cm), who underwent the SN-procedure. Only in case of SN metastases an inguinofemoral lymphadenectomy was performed. For the present study follow-up was completed until March 2015. RESULTS: Themedian follow-up was 105 months (range 0­179). The overall local recurrence ratewas 27.2% at 5 years and 39.5% at 10 years after primary treatment, while for SN-negative patients 24.6% and 36.4%, and for SN-positive patients 33.2% and 46.4% respectively (p = 0.03). In 39/253 SN-negative patients (15.4%) an inguinofemoral lymphadenectomy was performed, because of a local recurrence. Isolated groin recurrence rate was 2.5% for SN-negative patients and 8.0% for SN-positive patients at 5 years. Disease-specific 10-year survival was 91% for SN-negative patients compared to 65% for SN-positive patients (p b .0001). For all patients, 10-year disease-specific survival decreased from 90% for patients without to 69% for patients with a local recurrence (p b .0001).

[A woman with a vulvar swelling, a rare manifestation of the Klippel-Trenaunay-Weber syndrome]. / Een vrouw met een vulvaire zwelling, een zeldzame uiting van het Klippel-Trenaunay-Weber-syndroom.

A woman with a vulvar swelling, a rare manifestation of the Klippel-Trenaunay-Weber syndrome. - A 32-year-old woman presented with a vulvar swelling. The swelling had always been there but had increased after her last pregnancy, 5 years earlier. Because of progressive complaints, such as pain and a feeling of pressure, she now wished surgical correction. The swelling turned out to be varicosis of the right labium majus associated with the Klippel-Trenaunay-Weber syndrome. The vulvar swelling was removed by electrocoagulation. The pathological diagnosis was 'venous haemangioma'. The Klippel-Trenaunay-Weber syndrome is a congenital skin condition in which vascular angiomas, varicosis and trophic changes in the soft tissue and skeleton can arise. Vulvar involvement is rare. The abnormality can be removed surgically, for example by electrocoagulation. There is a chance of recurrence.

Adnexal masses in pregnancy.

With the widespread use of routine abdominal ultrasound examination during pregnancy, adnexal masses are observed with increasing frequency. Most patients are clinically asymptomatic at the time of presentation, and most of the adnexal masses detected during early pregnancy disappear during the first 16 weeks of pregnancy. Ovarian tumors are estimated to occur in about 1 in 1,000 pregnancies and of these 3% are malignant. Here we present an overview about frequency, diagnostic procedures and pathological characteristics of these ovarian tumors. Moreover, current modalities for treatment during pregnancy are summarized. Surgical treatment of the adnexal masses has to be performed with adequate staging and debulking equal to the treatment of non-pregnant women. However, whereas during organogenesis abortion has to be considered prior to chemotherapy, later in pregnancy surgical debulking as complete as possible, followed by taxol-platinum chemotherapy is indicated. If the fetus is not viable at the time of primary surgery, neoadjuvant chemotherapy and complementation of surgery after delivery of the baby should be performed. It should be stressed that chemotherapy for ovarian cancer applied during pregnancy appears to be safe. However, no studies have evaluated the long-term consequences for children exposed to intra-uterine chemotherapy. Aspiration of cysts should be avoided, as the correlation between the histological evaluation of an ovarian malignancy and the cytological evaluation of aspirates is poor. Moreover, spillage of malignant cysts is hazardous for the patient.

Aneurysm of the umbilical vein: case report and review of literature.

We report a case of aneurysm of the umbilical vein, causing fetal death at 41 weeks gestation. We conclude that these aneurysms are a complication of congenital thinning of the vessel wall and want to emphasize that in stillbirths the cause of death may only be revealed by careful placental examination, including the umbilical cord.

Plasma testosterone surge and luteinizing hormone beta (LH-beta) following parturition: lack of association in the male rat.

Studies examining the role of luteinizing hormone (LH) in the initiation of the postnatal surge of testosterone in the male rat have produced ambiguous results. We examined the pattern of postnatal LH secretion in the newborn male rat, coincident with plasma testosterone levels, using a specific monoclonal antibody for LH-beta. In some males, we attempted to block LH secretion and the postnatal testosterone surge by injecting males with a gonadotropin-releasing hormone (GnRH) antagonist, an LH antibody or progesterone immediately after delivery by cesarean section on day 22. Following injection, animals were immediately sacrificed (time 0) or housed in a humidified incubator maintained at 30 degrees C until sacrifice at 60, 120, 240, 360 or 480 min after delivery. Plasma from individual animals was measured subsequently for LH-beta and testosterone by radioimmunoassay. Results revealed a postnatal surge of testosterone which peaked at 2 h after delivery in males from all treatment groups. This testosterone surge was not accompanied by a postnatal rise in plasma LH-beta in any group. Administration of the GnRH antagonist or the ethanol vehicle produced a transient drop of approximately 25% in LH-beta levels at 60 min but did not decrease the postnatal testosterone surge in the same animals. Additional studies in untreated males and females born by cesarean section or natural birth also failed to reveal a postnatal rise in plasma LH-beta during the first 3 h after birth. Plasma levels in both sexes were significantly lower in animals delivered by cesarean section compared to natural birth.(ABSTRACT TRUNCATED AT 250 WORDS)

Decreased postnatal testosterone and corticosterone concentrations in rats following acute intermittent prenatal hypoxia without alterations in adult male sex behavior.

The prenatal and postnatal testosterone surges in the male rat are associated with neurobehavioral sexual differentiation of the brain. Both surges can be attenuated by maternal stress or other environmental factors that activate the maternal and/or fetal hypothalamic/pituitary/adrenal (HPA) axis during the last week of gestation. Since hypoxia is known to activate the HPA axis, we studied its effect during gestation on sexual differentiation in the male rat. We examined the influence of intermittent hypoxic exposure during gestation with respect to the postnatal testosterone surge and corticosterone levels, and subsequent development of adult reproductive and nonreproductive sexually dimorphic behaviors. Plasma testosterone and corticosterone concentrations of male neonates were measured after maternal exposure to acute, intermittent, prenatal hypoxia (9% O2 6 h/day from Day 15 to 21 of gestation). Relative to normoxic controls, acute, intermittent, prenatal hypoxia significantly attenuated the postnatal testosterone surge. Postpartum plasma corticosterone levels in these animals were also suppressed. In adulthood, prenatally hypoxic animals exhibited normal masculine sex behavior. Lordosis behavior in response to estrogen and progesterone priming was not significantly different between treatment groups. Saccharin preference, a nonreproductive, sexually dimorphic behavior, was not significantly influenced by prenatal hypoxic exposure. These results demonstrate that in the male acute intermittent prenatal hypoxia attenuates the postnatal testosterone surge. However, this reduction failed to result in significant alterations in the expression of sex related behaviors in adulthood.

Altered catecholaminergic behavioral and hormonal responses in rats following early postnatal hypoxia.

We have previously reported alterations in a battery of behavioral functions in the rat following both intermittent and chronic prenatal hypoxia. In this species, the critical brain growth spurt for the catecholaminergic neurotransmitter system takes place in the late gestational and early postnatal period. In addition, postnatal stress can modify adult hypothalamic-pituitary-adrenal responsiveness. Following a given stress, administration of dopaminergic/adrenergic agonists/antagonists may elucidate subtle changes that are not apparent in routine behavioral and endocrine tests. To test the hypothesis that early postnatal hypoxia affects development of the catecholaminergic system and, thus, alters functional outcome, we performed the following study. We exposed 25 litters of Sprague-Dawley rats, each consisting of 10 male pups, to hypoxia (10.5% inspired O2) for 6 h/day (0900 to 1500 h) from postnatal day (P) 2 to 10. We also had 25 control (C) litters. We then performed a series of behavioral tests in immature and mature animals. Body weights were significantly decreased in hypoxic (H) animals from P10 to P100. At P21 we tested locomotor activity in an open-field paradigm with drug challenge (apomorphine, a dopamine receptor agonist, 0.025 and 0.1 mg/kg; or haloperidol, a dopamine receptor antagonist, 0.2 and 0.4 mg/kg). Grooming activity was significantly decreased in H animals at both apomorphine concentrations, compared to controls. Moreover, rearing activity was significantly increased in H animals under basal conditions and when challenged with 0.1 mg/kg apomorphine. Apomorphine (1.0 mg/kg)-induced stereotypy at P39 was significantly increased in H animals compared to controls. Open-field activity at 80 days revealed no significant differences in drug responsiveness between H and C animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Altered adult sexual behavior in the male rat following chronic prenatal hypoxia.

The last week of gestation is a critical period for the sexual differentiation of the brain in the rat. Exposure to prenatal stress during this period has been shown to demasculinize and/or feminize adult male sexual behavior. Many of the neurochemical and endocrine responses to hypoxia are similar to that observed under stressful conditions such as restraint stress. Therefore, we examined the postnatal consequences on reproductive and nonreproductive sexually dimorphic behaviors in male offspring of dams exposed to chronic hypoxia during the last week of gestation. In addition, we examined sensorimotor development in offspring of both sexes. Pregnant Sprague-Dawley dams were exposed to continuous hypoxia (10.5% O2 from gestational day 15 to 21). Offspring were weaned at 22 days of age and group housed. Behavioral tests were conducted with littermate representatives. In adulthood, male rats prenatally exposed to hypoxia had significantly delayed initiation latencies of masculine sexual behavior and decreased number of ejaculations, but did not display a significant increase in feminine sex behavior potentials. Developmentally, animals exposed to prenatal hypoxia did not differ significantly from controls with respect to day of eye or ear opening, or the in times of righting reflex, negative geotaxis or cliff avoidance. Wire hanging latencies in hypoxic exposed animals were significantly greater than controls around the time of eye opening, but did not differ at earlier or later ages. A significant effect of hypoxia was detected on stride length at 95 days of age, but other aspects of gait patterns were similar to controls. No group differences in gait patterns were observed at 17 or 45 days of age. In addition, no significant differences were observed in open field activity, circadian locomotor activity, saccharin preference, or Morris water maze test. This hypoxia regimen did not influence the occurrence of the prenatal or postnatal surge of plasma testosterone. Overall, these results provide some evidence that, in males, mild, chronic prenatal hypoxia may result in incomplete masculinization of adult reproductive behavior in the absence of overt changes in perinatal testosterone surges.

Behavioral and neurochemical sequelae in young rats of antenal hypoxia.

To test the hypothesis that perinatal hypoxia may have postnatal consequences via à vis learning memory, and neurochemical sequelae, we exposed pregnant Sprague-Dawley rats to 10.5% O2 for 4 h per day (0800-1200 h) or continuously from gestional day E15 to E20. On E20 we quantified ornithine decarboxylase activity and polyamine concentrations in fetal brain. We also conducted behavioral tests from postnatal day P3 to P110. Relatively mild antenatal hypoxia resulted in altered learning, memory, and delayed maturation of early developmental sensorimotor function. These behavioral changes disappeared at various postnatal ages, depending on the function. Perinatal hypoxia also altered the pharmacological response to dopaminergic drugs. In addition, antenatal hypoxia feminized a male nonreproductive sexual behavior, that of saccharin preference. Acute hypoxia also resulted in an increase in the enzyme ornithine decarboxylase and polyamines, which may affect brain development.

Behavioral sequelae in young rats of acute intermittent antenatal hypoxia.

Several studies have examined behavioral sequelae of acute or chronic pre- or postnatal hypoxia. However, few of these tested a large battery of behavioral functions, particularly those following relatively mild, intermittent hypoxia. Also, in few studies were the hypoxic pups cross-fostered or the experimenter blinded as to experimental group. In addition, in almost no studies were concomitant hypoxic-induced brain biochemicals measured. The present study tested the hypotheses that mild, intermittent antenatal hypoxia can lead to long-term alterations in neurobehavioral development, as well as neurochemical changes.