A prospective, comparative study on robotic versus open-surgery hysterectomy and pelvic lymphadenectomy for endometrial carcinoma.

OBJECTIVES: The aim of this study was to compare surgical outcome, patient recovery, and costs between robot-assisted laparoscopy and laparotomy in women undergoing hysterectomy, bilateral salpingo-oophorectomy (BSOE), and pelvic lymphadenectomy for endometrial carcinoma. METHODS: Women undergoing hysterectomy, BSOE, and pelvic lymphadenectomy for endometrial carcinoma, according to regional guidelines, were prospectively, concurrently, and consecutively included from September 2010 to December 2012. Surgical outcomes such as operative time, estimated blood loss (EBL), number of lymph nodes retrieved, and complications were analyzed together with hospital stay, days until normal active daily living was retrieved, patient satisfaction with the length of the hospital stay, and cost per patient. Robot-assisted laparoscopy was performed on all cases at the Sahlgrenska University Hospital, and laparotomy was performed on all cases at 3 regional hospitals. RESULTS: Forty women underwent robot-assisted laparoscopy, and 48 underwent laparotomy. There were no differences in age, body mass index, histology, or retrieved lymph nodes. Operative time was significantly shorter in the robot-assisted laparoscopy group (P < 0.0001). The EBL was lower and hospital stay was shorter in the robot-assisted laparoscopy group (P < 0.0001). There was no statistical difference in complications between the groups, and both groups found hospital stay duration satisfactory. In the robot-assisted laparoscopy group, active daily living was normal within 5 days postoperatively, compared with 14 days in the laparotomy group (P < 0.0001). Calculated costs per treated patient did not differ statistically between the groups. CONCLUSIONS: Compared with laparotomy and robot-assisted laparoscopic hysterectomy, BSOE pelvic lymphadenectomy for endometrial carcinoma was associated with significantly shorter operative time, hospital stay, and lower EBL. Patients recovered more quickly after robot-assisted laparoscopy, with equal costs number of retrieved lymph nodes, compared with laparotomy.

The future of human uterus transplantation.

The only untreatable subgroup of female infertility is absolute uterine factor infertility (AUFI), which is due to congenital or surgical absence of a uterus or presence of a nonfunctional uterus. The solitary option for a woman with AUFI to become a biological mother today is through a gestational surrogate mother, a procedure that is prohibited in Sweden and large parts of the world. Uterus transplantation (UTx) is a potential future treatment of AUFI. After extensive animal research, also involving non-human primates, a small number of human UTx cases have recently been performed. Here, we summarize the primate UTx experiments that have paved the way for the human UTx cases, which are described and analyzed in more detail. We also estimate how many women of fertile age are affected by AUFI and describe the causes. The ethics around UTx is complex and is also addressed.

First clinical uterus transplantation trial: a six-month report.

OBJECTIVE: To report the 6-month results of the first clinical uterus transplantation (UTx) trial. This type of transplantation may become a treatment of absolute uterine-factor infertility (AUFI). DESIGN: Prospective observational study. SETTING: University hospital. PATIENT(S): Nine AUFI women and their live uterine donors, the majority being mothers. INTERVENTION(S): Live-donor UTx and low-dose induction immunosuppression. MAIN OUTCOME MEASURE(S): Data from preoperative investigations, surgery and follow-up for 6 months. RESULT(S): Durations of donor and recipient surgery ranged from 10 to 13 hours and from 4 to 6 hours, respectively. No immediate perioperative complications occurred in any of the recipients. After 6 months, seven uteri remained viable with regular menses. Mild rejection episodes occurred in four of these patients. These rejection episodes were effectively reversed by corticosteroid boluses. The two graft losses were because of acute bilateral thrombotic uterine artery occlusions and persistent intrauterine infection. CONCLUSION(S): The results demonstrate the feasibility of live-donor UTx with a low-dose immunosuppressive protocol. CLINICAL TRIAL REGISTRATION NUMBER: NCT01844362.

Identification of a gene expression signature for survival prediction in type I endometrial carcinoma.

Endometrial cancer is the most common malignancy of the female reproductive tract. In many cases the prognosis is favorable, but 22% of affected women die from the disease. We aimed to study potential differences in gene expression between endometrioid adenocarcinomas from survivors (5-year survival) and nonsurvivors. Forty-five patients were included in the investigation, of which 21 were survivors and 24 were nonsurvivors. The tumors were analyzed with genome-wide expression array analysis, represented by 13,526 genes. Distinct differences in gene expression were found between the groups. A t-test established that 218 genes were significantly differentially expressed (p < 0.001) between the two survival groups, and in a cross-validation test 40 of the 45 (89%) tumors were classified correctly. The 218 differentially expressed genes were subjected to hierachical clustering analysis, which yielded two clusters both exhibiting over 80% homogeneity with respect to survival. When the additional constraint of fold change (FC > 2) was added the hierachical clustering yielded similar results. Stage I tumors are expected to have a favorable prognosis. However, in our tumor material there were six nonsurvivors with stage I tumors. Five out of six stage I nonsurvivors clustered in the nonsurvival fraction. Our findings suggest that a subgroup of early stage endometroid adenocarcinomas can be correctly classified as potentially aggressive by using molecular biology in combination with conventional markers, thereby providing a tool for a more accurate classification and risk evaluation of the individual patient.

Effect of lipopolysaccharide on global gene expression in the immature rat brain.

To improve the understanding of the molecular mechanisms whereby lipopolysaccharide (LPS) affects the immature brain, global gene expression following LPS exposure was investigated in neonatal rats. Brains (n = 5/time point) were sampled 2, 6, and 72 h after LPS and compared with age-matched controls. The mRNA from each brain was analyzed separately on Affymextrix GeneChip Rat Expression Set 230. The number of genes regulated after LPS were 847 at 2 h, 1564 at 6 h, and 1546 genes at 72 h. Gene ontology analysis demonstrated that, at both 2 and 6 h after LPS, genes associated with protein metabolism, response to external stimuli and stress (immune and inflammatory response, chemotaxis) and cell death were overrepresented. At 72 h, the most strongly regulated genes belonged to secretion of neurotransmitters, transport, synaptic transmission, cell migration, and neurogenesis. Several pathways associated with cell death/survival were identified (caspase-tumor necrosis factor alpha [TNF-alpha]-, p53-, and Akt/phosphatidylinositol-3-kinase (PI3 K)-dependent mechanisms). Caspase-3 activity increased and phosphorylation of Akt decreased 8 h after peripheral LPS exposure. These results show a complex cerebral response to peripheral LPS exposure. In addition to the inflammatory response, a significant number of cell death-associated genes were identified, which may contribute to increased vulnerability of the immature brain to hypoxia-ischemia (HI) following LPS exposure.

Lipopolysaccharide induces both a primary and a secondary phase of sensitization in the developing rat brain.

Data indicate that bacterial products in combination with other antenatal or postnatal exposures increase the risk of perinatal brain injury. We have previously shown that administration of lipopolysaccharide (LPS) 4 h before hypoxia-ischemia (HI) increases brain injury in 7-d-old rats. The mechanisms behind such sensitization are unclear, but contrasts against a preconditioning effect of LPS given 1-3 d before ischemia in adult animals. To investigate how the effects of LPS depend on the time interval between administration and HI in the developing brain, we evaluated the effect of varying time interval (2-72 h) between LPS and HI, the duration of HI (20 or 50 min), and age of the rat pups (postnatal d 4 or 7). Outcome was assessed by brain injury scoring of specific regions. We found that LPS reduced brain injury (by 78%) when administered 24 h before 50 min of HI. However, when LPS was administered 6 h before either 20 or 50 min of HI, brain injury was increased by 2026% and 137%, respectively. Even LPS given 72 h before HI increased injury, both when LPS was administered at postnatal d 4 (by 446%) and 7 (by 77%). In conclusion, LPS enhanced vulnerability in the developing brain both in the acute (4-6 h) and the chronic (72 h) phase after administration, whereas an intermediate interval between LPS and HI had the opposite effect. The long-term sensitizing effect of LPS has not been previously described.

Global gene expression in the immature brain after hypoxia-ischemia.

Ischemia induces a complex response of differentially expressed genes in the brain. In order to understand the specific mechanisms of injury in the developing brain, it is important to obtain information on global changes in the transcriptome after neonatal hypoxia-ischemia. In this study, oligonucleotide arrays were used to investigate genomic changes at 2, 8, 24, and 72 hours after neonatal hypoxia-ischemia, which was induced in 9-day-old mice by left carotid artery ligation followed by hypoxia (10% O2). In total, 343 genes were differentially expressed in cortex, hippocampus, thalamus, and striatum 2 to 72 hours after hypoxia-ischemia, when comparing ipsilateral with contralateral hemispheres and with controls, using the significance analysis for microarrays. A total of 283 genes were upregulated and 60 were downregulated, and 94% of the genes had not previously been shown after neonatal hypoxia-ischemia. Genes related to transcription factors and metabolism had mostly upregulated transcripts, whereas most downregulated genes belonged to the categories of ion and vesicular transport and signal transduction. Genes involved in transcription, stress, and apoptosis were induced early after the insult, and many new genes that may play important roles in the pathophysiology of neonatal hypoxia-ischemia were identified.

The role of glucose in brain injury following the combination of lipopolysaccharide or lipoteichoic acid and hypoxia-ischemia in neonatal rats.

We have previously shown that lipopolysaccharide (LPS) sensitizes the immature rat brain to subsequent hypoxic-ischemic (HI) injury; however, the underlying mechanisms remain unclear. In this study, we examined the role of glucose in the sensitizing effects of LPS and lipoteichoic acid (LTA) in combination with HI in 7-day-old rats. LPS/HI resulted in hypoglycemia which lasted 24 h and lactate levels were increased from 6 to 10 h after LPS administration. LPS/HI induced severe brain injury, which persisted 2 weeks after LPS/HI. Administration of glucose to LPS-treated animals with HI reduced brain injury in the cerebral cortex and hippocampus, while striatal damage remained. LTA/HI did not affect blood glucose, lactate or brain injury. In conclusion, enhanced blood glucose levels during HI after LPS administration conferred protection in some brain regions but not in the striatum, suggesting that alterations in glucose can only partly explain the sensitizing effect of LPS.