Metabolomics annotates ABHD3 as a physiologic regulator of medium-chain phospholipids.

All organisms, including humans, possess a huge number of uncharacterized enzymes. Here we describe a general cell-based screen for enzyme substrate discovery by untargeted metabolomics and its application to identify the protein α/ß-hydrolase domain-containing 3 (ABHD3) as a lipase that selectively cleaves medium-chain and oxidatively truncated phospholipids. Abhd3(-/-) mice possess elevated myristoyl (C14)-phospholipids, including the bioactive lipid C14-lysophosphatidylcholine, confirming the physiological relevance of our substrate assignments.

Fertility preserving surgery for carcinoma of the cervix.

PURPOSE OF REVIEW: Cervical cancer remains the second most common female malignancy. Screening programmes have reduced the overall incidence, predominantly in the western world; however, this has led to a disproportionate rise in the incidence of early-stage disease, with a related increase in demand, for fertility-sparing techniques to be developed. RECENT FINDINGS: Standard treatment for cervical cancer compromises fertility. A radical wide local excision of carefully selected early-stage tumours will allow conservation of the body of the uterus with a vaginoisthmic anastomosis enabling continuity of the vagina to be preserved following insertion of an isthmic cerclage suture. Pelvic node dissection may be performed at the same time by laparoscopic techniques. Over 900 cases have been performed and reported in the literature worldwide. Most have been carried out vaginally (radical vaginal trachelectomy and laparoscopic pelvic node dissection). A smaller number have been performed abdominally. There have been over 300 pregnancies reported with 196 live births. There has been a 10% significant prematurity rate with birth prior to 32 weeks. There have been 31 recurrences (4%), and 16 deaths (2%). SUMMARY: Radical vaginal trachelectomy appears safe when performed in centres with appropriate experience of radical vaginal surgery and laparoscopic techniques. The impact of this new approach questions traditional teaching, thus preserving potential fertility in up until now impossible circumstances.

Analysis of chemokines and chemokine receptor expression in ovarian cancer ascites.

PURPOSE: Ascitic disease is a common occurrence in human ovarian cancer, but it is unclear how the cellular composition of ascitic fluid is determined. Because chemokines can determine host cell infiltration in solid ovarian cancer, we assessed CC chemokine protein and CC chemokine receptor expression in ovarian cancer ascites. EXPERIMENTAL DESIGN: We used reverse transcription-PCR and RNase protection assay to determine CC chemokine and chemokine receptor mRNA expression and ELISA to measure CC chemokine protein levels. Flow cytometry was used to identify cell populations and their chemokine receptor protein expression. RESULTS: mRNA for the CC chemokines CCL2, -3, -4, -5, -8, and -22 was expressed in cell isolates from ascites samples, and the corresponding proteins were detected in ascitic fluid. mRNA for CC chemokine receptors CCR1, -2a, -2b, -3, -4, -5, and -8 was detected in cells from ascites. Fluorescence-activated cell-sorting analysis showed variable numbers of macrophages and CD3(+) T lymphocytes (predominantly CD4(+)) within ovarian cancer ascites. CD14(+) macrophages within ascites consistently expressed protein for CCR1, -2, and -5. CCR1 was expressed by >60% of all T cells, but more CD4(+) than CD8(+) T cells expressed CCR2 and -5. A direct correlation was found between the CCL5 concentration and CD3(+) T-cell infiltration. CONCLUSIONS: We conclude that there is a complex chemokine/chemokine receptor network in ovarian cancer ascites. However, associations between chemokine receptor expression, chemokine levels, and cell counts were limited.

Differences in hand movements and task completion times between laparoscopic, robotically assisted, and open surgery: an in vitro study.

Surgical dexterity depends on economy and precision of movements, and this can be objectively measured using electromagnetic motion analysis. We have assessed the differences in hand movements and task completion times between open, laparoscopic and robotically assisted surgery during an exercise performed in vitro. A standard surgical exercise was performed using open, standard laparoscopic (SL) and robotically assisted laparoscopic (RAL) approaches. The total duration of the exercise was studied along with the number and duration of movements required to complete the exercise in each surgical modality. The time taken to complete the exercise was significantly longer in both the SL and RAL approaches when compared to the open route. However, it was found that RAL had significantly decreased number of movements (mean difference = 24 movements, P < 0.006) but a longer duration of each movement when compared to SL (mean difference = 0.13 s, P < 0.001). This study shows objectively that the exercise took longer to complete using the RAL approach than the standard open approach. However, RAL had more purposeful movements and required fewer movements to complete the exercise compared to SL.

Cytoreductive surgery in ovarian cancer.

As the overall prognosis for patients with ovarian cancer is poor, the management of this condition should be restricted to expert multi-disciplinary teams in gynaecological oncology. Apparent early stage ovarian cancer requires accurate and complete staging so that potential sites for metastases are not missed. Omitting adequate staging may have significant consequences including a negative impact on survival rates in young patients. The challenge with advanced ovarian cancer is to obtain a detailed appreciation of the extent of disease. This information allows treatment with primary chemotherapy if the cancer is considered to be inoperable and/or the general condition of the patient renders her unfit for appropriate surgery. Available data would suggest that a 5-year survival rate of 50% is only possible for those patients who have had complete cytoreduction of all tumour. Therefore, the best surgical option for patients with advanced ovarian cancer is a 'complete' primary surgical procedure that achieves complete clearance of the abdominal cavity rather than 'optimal' surgery that leaves tumour nodules up to 1 cm in diameter in situ in the patient.