Does virtual reality simulation have a role in training trauma and orthopaedic surgeons?

Aims: The aim of this study was to assess the current evidence relating to the benefits of virtual reality (VR) simulation in orthopaedic surgical training, and to identify areas of future research. Materials and Methods: A literature search using the MEDLINE, Embase, and Google Scholar databases was performed. The results' titles, abstracts, and references were examined for relevance. Results: A total of 31 articles published between 2004 and 2016 and relating to the objective validity and efficacy of specific virtual reality orthopaedic surgical simulators were identified. We found 18 studies demonstrating the construct validity of 16 different orthopaedic virtual reality simulators by comparing expert and novice performance. Eight studies have demonstrated skill acquisition on a simulator by showing improvements in performance with repeated use. A further five studies have demonstrated measurable improvements in operating theatre performance following a period of virtual reality simulator training. Conclusion: The demonstration of 'real-world' benefits from the use of VR simulation in knee and shoulder arthroscopy is promising. However, evidence supporting its utility in other forms of orthopaedic surgery is lacking. Further studies of validity and utility should be combined with robust analyses of the cost efficiency of validated simulators to justify the financial investment required for their use in orthopaedic training. Cite this article: Bone Joint J 2018;100-B:559-65.

Computed tomographic anatomy of the nasal cavity, paranasal sinuses and tympanic cavity of the koala.

OBJECTIVE: To use cross-sectional imaging (helical computed tomography (CT)) combined with conventional anatomical dissection to define the normal anatomy of the nasal cavity and bony cavitations of the koala skull. METHODS: Helical CT scans of the heads of nine adult animals were obtained using a multislice scanner acquiring thin slices reconstructed in the transverse, sagittal and dorsal planes. Subsequent anatomical dissection permitted confirmation of correct identification and further delineation of bony and air-filled structures visible in axial and multiplanar reformatted CT images. RESULTS: The nasal cavity was relatively simple, with little scrolling of nasal conchae, but bony cavitations were complex and extensive. A rostral maxillary recess and ventral conchal, caudal maxillary, frontal and sphenoidal paranasal sinuses were identified and characterised. Extensive temporal bone cavitation was shown to be related to a large epitympanic recess. CONCLUSIONS: The detailed anatomical data provided are applicable to future functional and comparative anatomical studies, as well as providing a preliminary atlas for clinical investigation of conditions such as cryptococcal rhinosinusitis, a condition more common in the koala than in many other species.

History of frequent gum chewing is associated with higher unstimulated salivary flow rate and lower caries severity in healthy Chinese adults.

This was a single-center, prospective, cross-sectional study stratified by age and gender with the objective of determining the relationship between gum chewing history, salivary flow, and dental caries severity in adults. We enrolled 191 subjects aged 18-65 years who underwent assessments for gum chewing history, unstimulated salivary flow rate, salivary pH, and caries severity. Unstimulated salivary flow rate tended to decline with increasing age (p = 0.04), and significant differences in unstimulated salivary flow rate were also found for males (0.58 ± 0.32 ml/min) versus females (0.48 ± 0.30 ml/min) (p = 0.02). Weekly gum chewing frequency was greater in younger subjects (p = 0.001) while no age group differences were noted in pieces per day or chewing duration. Gum chewing habits were similar in males and females. A multivariate model demonstrated that only days per week chewing gum (p < 0.001) and gender (p = 0.007) were predictive of unstimulated salivary flow rate (R(2) = 0.40). Mean caries severity scores, assessed via ICDAS II and DMFT, increased with age. In multivariate analysis, age was positively associated with ICDAS (p = 0.001) and days per week chewing gum was negatively associated with ICDAS (p = 0.004), indicating that caries severity increased with age, and that days of chewing provided an inverse effect, with increased days of chewing being associated with decreased severity of caries. Overall, a history of frequent gum chewing is associated with higher unstimulated salivary flow rate and lower caries severity.

Nanopost plasmonic crystals.

We describe a class of plasmonic crystal that consists of square arrays of nanoposts formed by soft nanoimprint lithography. As sensors, these structure show somewhat higher bulk refractive index sensitivity for aqueous solutions in the visible wavelength range as compared to plasmonic crystals consisting of square arrays of nanowells with similar dimensions, with opposite trends for the case of surface bound layers in air. Three-dimensional finite-difference time-domain simulations quantitatively capture the key features and assist in the interpretation of these and related results.

Fluid therapy for acute bacterial meningitis.

BACKGROUND: Acute bacterial meningitis remains a disease with high mortality and morbidity rates. However, with prompt and adequate antimicrobial and supportive treatment, the chances for survival have improved, especially in infants and children. Careful management of fluid and electrolyte balance is an important supportive therapy. Both over- and under-hydration are associated with adverse outcomes. OBJECTIVES: To evaluate differing volumes of fluid given in the initial management of bacterial meningitis. SEARCH STRATEGY: We searched the Cochrane Acute Respiratory Infection Group's trials register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 1), MEDLINE (1966 to March 2007), EMBASE (1980 to March 2007), and CINAHL (1982 to February 2007). SELECTION CRITERIA: Randomised controlled trials of differing volumes of fluid given in the initial management of bacterial meningitis were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Six trials were identified in the initial search. On careful inspection three of these met the inclusion criteria. Data were extracted and trials were assessed for quality by all four of the original review authors (one author, R.O.W. has died since the original review, see acknowledgements). Data were combined for meta-analysis using relative risks for dichotomous data or weighted mean difference for continuous data. A fixed-effect statistical model was used. MAIN RESULTS: The largest of the three trials was conducted in settings with high mortality rates. The meta-analysis found no significant difference between the maintenance-fluid and restricted-fluid groups in number of deaths (RR 0.82, 95% CI 0.53 to 1.27); acute severe neurological sequelae (RR 0.67, 95% CI 0.41 to 1.08); or in mild to moderate sequelae (RR 1.24, 95% CI 0.58 to 2.65). However, when neurological sequelae were defined further, there was a statistically significant difference in favour of the maintenance-fluid group in regard to spasticity (RR 0.50, 95% CI 0.27 to 0.93), seizures at both 72 hours (RR 0.59, 95% CI 0.42 to 0.83) and 14 days (RR 0.19, 95% CI 0.04 to 0.88), and chronic severe neurological sequelae at three-months follow up (RR 0.42, 95% CI 0.20 to 0.89). AUTHORS' CONCLUSIONS: Some evidence supports maintaining intravenous fluids rather than restricted them in the first 48 hours, in settings with high mortality rates and where patients present late. However, where children present early and mortality rates are lower there is insufficient evidence to guide practice.

Fluid therapy for acute bacterial meningitis.

BACKGROUND: Acute bacterial meningitis remains a disease with high mortality and morbidity rates. However, with prompt and adequate antimicrobial and supportive treatment, the chances for survival have improved, especially in infants and children. Careful management of fluid and electrolyte balance is an important supportive therapy. Both over and under hydration are associated with adverse outcomes. OBJECTIVES: The objective of this review was to evaluate differing volumes of fluid given in the initial management of bacterial meningitis. SEARCH STRATEGY: We searched the Cochrane Acute Respiratory Infection Group's trials register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to March 2005), EMBASE (1980 to December 2004), and CINAHL (1982 to February 2005). References from relevant articles were searched and authors contacted where necessary. In addition, we contacted experts in the field for unpublished works. SELECTION CRITERIA: Randomised controlled trials of differing volumes of fluid given in the initial management of bacterial meningitis were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Six trials were identified in the initial search. On careful inspection three of these met the inclusion criteria. Data were extracted and trials were assessed for quality by all four reviewers. Data were combined for meta-analysis using relative risks for dichotomous data or weighted mean difference for continuous data. A fixed-effect statistical model was used. MAIN RESULTS: The largest of the three trials was conducted in settings with high mortality rates. The meta-analysis found no significant difference between the maintenance-fluid and restricted-fluid groups in number of deaths (RR 0.82, 95% CI 0.53 to 1.27); acute severe neurological sequelae (RR 0.67, 95% CI 0.41 to 1.08); or in mild to moderate sequelae (RR 1.24, 95% CI 0.58 to 2.65). However, when neurological sequelae were defined further, there was a statistically significant difference in favour of the maintenance-fluid group in regard to spasticity (RR 0.50, 95% CI 0.27 to 0.93), seizures at both 72 hours (RR 0.59, 95% CI 0.42 to 0.83) and 14 days (RR 0.19, 95% CI 0.04 to 0.88), and chronic severe neurological sequelae at three-months follow up (RR 0.42, 95% CI 0.20 to 0.89). AUTHORS' CONCLUSIONS: There is some evidence to support the use of intravenous maintenance fluids in preference to restricted fluid intake in the first 48 hours in settings with high mortality rates and where patients present late. However, where children present early and mortality rates are lower there is insufficient evidence to guide practice.

Detecting the dangerous, violent or criminal patient: an analysis of referrals to maximum security psychiatric care.

Britain's high security hospitals provide care for mentally disordered patients who have dangerous, violent or criminal propensities. The State Hospital, Carstairs, takes referrals from the population of Scotland and Northern Ireland. This retrospective case-control study describes the sociodemographic and clinical characteristics of referrals (n=149) to the State Hospital during a 12-month period, and delineates differences between admitted (n=57) and rejected (n=92) patients. The referrals had an average age of 31.1 years, and were mostly male (86.6%), single (64.4%) and unemployed (90.6%). Admitted patients were more likely to have a criminal history, to be psychotic, to have a family history of mental disorder and to be viewed by the assessor as having psychotic beliefs which contributed to the behaviour or alleged offence leading to the referral. Rejected patients were more likely to have been remanded to prison or assessed by specialist registrars. Patients admitted to high security psychiatric care are more likely to show dangerous behaviour secondary to psychosis. These findings are in keeping with the requirements of mental health legislation and the admissions policy.

A phase III placebo-controlled study in advanced head and neck cancer using intratumoural cisplatin/epinephrine gel.

Patients with recurrent or refractory head and neck squamous cell carcinoma received cisplatin/epinephrine injectable gel or placebo gel injected directly into the clinically dominant tumour. The double-blind phase III trial comprised of up to 6 weekly treatments over 8 weeks, 4 weekly evaluation visits, and then monthly follow-up; open-label dosing began as needed after three blinded treatments. Tumour response was defined as complete (100% regression) or partial (50-99% regression) sustained for > or =28 day, and patient benefit as attainment of palliative or preventive goals prospectively selected by investigators and patients. With cisplatin/epinephrine gel, 25% (14 out of 57) of tumours responded (16% complete regression, 9% partial regression), vs 3% (one out of 35, complete regression) with placebo (P=0.007). Patient benefit was positively associated with target tumour response in the blinded period among cisplatin/epinephrine gel recipients (P=0.024): 43% (six out of 14) of responders benefited, vs 12% (five out of 43) of non-responders. The most frequent adverse event was pain during injection and the next most frequent was local cytotoxic effects consistent with the gel's mode of action. Systemic adverse events typical of intravenous cisplatin were uncommon. Intratumoural therapy with cisplatin/epinephrine gel provided safe, well-tolerated, effective palliative treatment for patients with locally advanced head and neck squamous cell carcinoma, who lack other satisfactory treatment options.

A prognostic model for ovarian cancer.

About 6000 women in the United Kingdom develop ovarian cancer each year and about two-thirds of the women will die from the disease. Establishing the prognosis of a woman with ovarian cancer is an important part of her evaluation and treatment. Prognostic models and indices in ovarian cancer should be developed using large databases and, ideally, with complete information on both prognostic indicators and long-term outcome. We developed a prognostic model using Cox regression and multiple imputation from 1189 primary cases of epithelial ovarian cancer (with median follow-up of 4.6 years). We found that the significant (P< or = 0.05) prognostic factors for overall survival were age at diagnosis, FIGO stage, grade of tumour, histology (mixed mesodermal, clear cell and endometrioid versus serous papillary), the presence or absence of ascites, albumin, alkaline phosphatase, performance status on the ZUBROD-ECOG-WHO scale, and debulking of the tumour. This model is consistent with other models in the ovarian cancer literature; it has better predictive ability and, after simplification and validation, could be used in clinical practice.

The omega-hydroxyceramides of pig epidermis are attached to corneocytes solely through omega-hydroxyl groups.

The cornified outer cells of mammalian epidermis possess a monolayer of omega-hydroxyceramides that are ester-linked to the exterior of a cross-linked protein envelope. In the present study, conclusive evidence was sought on which of the ceramide hydroxyl groups are involved in the linkage to protein. This was obtained by derivatizing all free hydroxyl groups in isolated solvent-extracted porcine stratum corneum using triisopropylsilyl (TIPS) chloride in pyridine in the presence of silver nitrate. After an 18-h reaction, the tissue was recovered, rinsed, and the derivatized ceramides were then released from protein linkage by hydrolysis with 1M KOH in 95% methanol. This gave a single ceramide product that was shown by nuclear magnetic resonance to contain two triisopropyl groups. Acetylation of the product using acetic anhydride in pyridine resulted in a downfield shift of the NMR signal for the omega-methylene protons, showing that it was the omega-hydroxyl that was free in the initial reaction product, and subsequently was acetylated. These results show that all of the omega-hydroxyceramides of corneocyte lipid envelopes are attached to protein through their omega-hydroxyl groups.

A new 6-hydroxy-4-sphingenine-containing ceramide in human skin.

A new ceramide consisting of 6-hydroxysphingosine linked to a non-hydroxyacid was found in human epidermal lipid. This ceramide was sought because its fatty acid and sphingoid moieties are present in other combinations in human epidermal ceramides. To isolate the new ceramide, the mixture of ceramides in human epidermal lipid was first separated into fractions by thin-layer chromatography (TLC), and then each fraction was further purified by TLC after acetylation of all hydroxyl groups. TLC after acetylation revealed that one of the fractions isolated in the first TLC step contained two components, namely, the ceramide consisting of sphingosine linked to an alpha-hydroxyacid and an unknown ceramide. The new ceramide constituted about 9% of the total ceramides, and was shown by NMR spectroscopy to be N-acyl-6-hydroxysphingosine.

X-ray diffraction analysis of isolated skin lipids: reconstitution of intercellular lipid domains.

Low- and wide-angle X-ray diffraction were used to determine the structural organization of lipids isolated from the stratum corneum extracellular matrix that forms the major water permeability barrier in mammalian epidermis. Hydrated pig skin ceramides gave a single low-angle reflection of about 62 angstroms and a wide-angle-reflection at 4.15 angstroms. The addition of either cholesterol or fatty acid, the other major lipid components of the skin stratum corneum extracellular matrix, modified this diffraction pattern, depending on the lipid mole ratios. In the absence of water, lipid mixtures exhibited lipid phase separation, as shown by low- and wide-angle reflections typical of a separate cholesterol phase. However, a hydrated 2:1:1 mole ratio of ceramide:cholesterol:palmitic acid (similar to that found in stratum corneum) produced a diffraction pattern with a single sharp wide-angle reflection at 4.10 angstroms and low-angle reflections which indexed as the first eight orders of a single repeat period of 130 angstroms. The repeat period and intensity distribution of the low-angle data were similar to those found in intact stratum corneum [White et al. (1988) Biochemistry 27, 3725-3732; Bouwstra et al. (1994) Biochim. Biophys. Acta 1212, 183-192]. Higher concentrations of cholesterol or palmitic acid resulted in lipid phase separations. The 130 angstrom repeat period decreased only about 3 angstroms as water was removed by incubation in low-relative humidity atmospheres. The 130 angstrom repeat period depended on the presence of a particular ceramide, N-(omega-acyloxy)-acylsphingosine, which is found only in the epidermis. In contrast, 2:1:1 mixtures of brain ceramide:cholesterol:palmitic acid gave reflections of 56 and 34 angstroms. These results indicate that a structure with dimensions similar to those of the lamellar repeating unit found in skin stratum corneum does not depend on the presence of protein but does depend on the presence of specific skin ceramides and appropriate concentrations of cholesterol and fatty acid.

Free sphingosines of human skin include 6-hydroxysphingosine and unusually long-chain dihydrosphingosines.

Ceramides containing 6-hydroxysphingosine, a previously unknown long-chain base, have recently been found in human skin. The present study investigated whether human skin also contains 6-hydroxysphingosine as the free base. Human skin surface lipids were obtained by washing with ethanol. A fraction enriched in sphingoid bases was isolated by preparative thin-layer chromatography and reacted with 2,4-dinitrofluorobenzene. The resulting N-dinitrophenyl derivatives were separated by thin-layer chromatography into three components, the most polar of which accounted for 15% of the total. After acetylation of the hydroxyl groups and repurification, each component was examined by nuclear magnetic resonance spectroscopy. The spectrum of the most polar of the derivatives indicated that it was 6-hydroxysphingosine or homologues of that substance. The spectra of the other two derivatives were virtually identical to those of derivatives prepared from authentic sphingosine and dihydrosphingosine. The chain-length distributions of the skin sphingoid bases were examined by gas chromatography after conversion of the dinitrophenyl acetates to dinitrophenyl trimethylsilyl derivatives. The analysis showed that the sphingosines and 6-hydroxysphingosines ranged from 17 to 22 carbons in length, with the 18- and 20-carbon species predominating. Surprisingly, the dihydrosphingosines included species with up to 26 carbons, with the 24-, 25-, and 26-carbon species accounting for about half of the total. Examination of the sphingoid bases of pig epidermis indicated that 6-hydroxysphingosine was not present and that the major chain length in the dihydrosphingosines was the 22-carbon species.

6-Hydroxy-4-sphingenine in human epidermal ceramides.

The solvent-extractable lipids of human epidermal stratum corneum consist predominantly of ceramides. In addition two non-extractable ceramides are chemically bound to the stratum corneum protein. One of the bound ceramides, constituting 50% of the bound lipids, was previously shown to consist of very long chan omega-hydroxyacids in amide linkage with sphingosine. The second bound caramide, which forms 25% of the bound lipids, was shown to contain the same hydroxyacids, but the sphingoid base was neither sphingosine nor phytosphingosine. In the present study, the undefined bound ceramide was shown by NMR and chemical procedures to be the omega-hydroxyacid derivative of a new base, 6-hydroxy-4-sphingenine. In addition, a ceramide previously known to constitute 25% of the extractable human stratum corneum ceramides has been found to contain the same novel sphingoid base, amide-linked to long-chain alpha-hydroxyacids. Finally, a new acylceramide has been isolated and identified that consists of very long chain omega-hydroxyacids in amide linkage with the novel sphingolipid, with fatty acids esterified wit the terminal hydroxyl group of the hydroxyacid.

Adolescents in a therapeutic community: treatment implications for teen survivors of traumatic experiences.

This article describes an adolescent with a history of severe traumatic experiences and treatment in a residential program for chemically dependent, severely emotionally disturbed youths between the ages of 12 and 18. It begins with a description of the long-term treatment program, the types of clients admitted, and the treatment activities provided. Basic findings from an outcome study conducted within the program made predictions regarding the length of time of residential treatment for drug addicted, severely emotionally disturbed adolescents regardless of trauma history. Pretreatment psychiatric functioning was addressed by utilizing GAF scores from the DSM-III-R for each of the participants in the study. Of 102 participants in the study, 34 were survivors of sexual abuse, physical abuse, or devastating natural disasters. A clinical case of a traumatized adolescent is presented in relation to adolescent identity, the distinction between adolescent and adult treatment, and a variety of treatment strategies that can influence an abused adolescent's long-term recovery from both addiction and trauma, including retention in treatment, the developmental stage of adolescence, identification and diagnosis of trauma during adolescence, building a working alliance, individual psychotherapy, psychopharmacology as an aid to psychotherapy, psychological debriefing, and group psychotherapy.

The relationship between tests of lung function and three chest radiological scoring systems in patients with cystic fibrosis.

The chest radiographs and lung function tests of 41 patients attending the cystic fibrosis clinic at Royal Prince Alfred Hospital were reviewed. The chest radiographs were scored using three different scoring systems: the Shwachman and Kulczycki system (as modified by Doershuk), the National Institute of Health (NIH) system described by Taussig in 1973 and the Brasfield system. The scores were correlated with lung function tests. Significant correlations were found between the radiological scores and the respiratory variables; the best correlation was with the forced expiratory volume in one second (FEV1 % predicted). All three scoring systems showed a high degree of reproducibility of scores when a second radiologist was asked to score the same radiographs independently. The difference in scores between the radiologists was not significant for the NIH and the Brasfield systems. The Brasfield system is, however, the system of choice because it allows the assessment of all the major pathological features seen in cystic fibrotic chest films and consistently has the best agreement with all the lung function variables. It was also found that radiological evidence of lung hyperinflation may not be a good indicator of disease progression.

Sebaceous gland activity and serum dehydroepiandrosterone sulfate levels in boys and girls.

BACKGROUND AND DESIGN: Increases in sebaceous gland activity are often the earliest sign of the approach of puberty in children. These increases have been attributed to increases in the secretion of adrenal androgens, but the supporting data are sparse and are based on measurements of urinary, rather than serum, androgen concentrations. In this study, we examined sebum composition, serum levels of dehydroepiandrosterone sulfate, and pubertal stage in 111 boys and girls, aged 2 to 15 years. Sebum composition was evaluated by measuring the ratio of wax esters/(cholesterol + cholesterol esters), a ratio known to increase with increasing sebaceous gland activity. RESULTS: Both wax esters/(cholesterol + cholesterol esters) ratios and serum dehydroepiandrosterone sulfate levels began to increase in children 7 to 10 years old. These changes occurred in many children before the appearance of any physical signs of puberty. Wax esters/(cholesterol + cholesterol esters) ratios were correlated with dehydroepiandrosterone sulfate levels in both boys and girls. In prepubertal children, the regression lines passed through the origin. In subjects who were in early or late puberty, the y intercepts of the regression lines had positive values. CONCLUSION: Adrenal androgens appear to be the major determinants of sebaceous gland activity during the prepubertal period and to be additive to another hormone or hormones during puberty.

Sebaceous gland lipids.

Human sebum contains squalene, wax esters, triglycerides, cholesterol esters, and possibly free cholesterol. The fatty acids of the ester lipids include species with chain branching or with unusual double-bond positions. The alcohol moieties of the wax esters contain unusual chain types similar to those of the fatty acids. Genetic and hormonal factors cause individual differences in sebaceous lipid composition. Genetic factors seem to influence the proportions of the various types of branched-chain fatty acids. Androgenic stimulation of the glands causes an increase in lipid synthesis, and therefore in the ratio of endogenously synthesized lipid to exogenous lipid. Because the endogenously synthesized lipids tend to be different from lipids that are derived exogenously, the overall composition of the secretion changes. Differences in sebum composition are particularly evident when the sebum of prepubertal children is compared with that of young adults. One difference that may be of clinical significance is the different concentrations of linoleate. Higher concentrations of sebum linoleate may protect young children from comedonal acne by preventing an essential fatty acid deficiency from developing in the follicular epithelium.

A phase I and pharmacology study of GR63178A, a water-soluble analogue of mitoquidone.

GR63178A is a water-soluble analogue of mitoquidone, a pentacyclic pyrroloquinone. This group of drugs exhibit a novel structure and activity against several murine solid tumours and xenografts. In the present phase I study the toxicity and pharmacokinetics of GR63178A given on 5 consecutive days of a 21-day cycle were examined. A total of 24 patients presenting with a wide range of tumours were treated at 5 doses escalated to reach the maximal tolerated dose (MTD). Linear pharmacokinetics was documented over the dose range studied, and there was no difference in parent drug handling between day 1 and day 4 of dosing. A number of metabolites were detected. The toxicity profile was unusual in that pain occurred in 20/24 patients, most often at the site of known disease. This was the dose-limiting toxicity. Other side effects included nausea and vomiting (23/24), phlebitis at the infusion site (6/24) and headache (7/24). No treatment response was seen in this study. The MTD was demonstrated to be 160 mg/m2 daily (total, 800 mg/m2 per treatment cycle). The drug has now entered phase II trials at 120 mg/m2 daily x 5, repeated every 21 days.

Cisplatinum and prednimustine, an active regimen for advanced epithelial ovarian cancer.

80 patients with advanced epithelial ovarian carcinoma were treated for 6 months with cisplatinum and prednimustine following initial surgery. Response to treatment was assessed by second-look surgery. The objective response rate was 69% with 38% achieving a complete response for up to 55 months. The toxicity of this regimen was acceptable. Statistically, de-bulking or partial de-bulking had a significant beneficial effect on the likelihood of a complete response. The best survival figures were associated with maximum de-bulking. The combination of cisplatinum and prednimustine is a new and active regimen for operable advanced epithelial ovarian carcinoma.