Predicting psychological distress in advanced ovarian cancer patients during the COVID-19 pandemic.

PURPOSE: This longitudinal study investigated distress rates in patients with advanced ovarian cancer during the COVID-19 pandemic and examined whether time, illness representations, and coping strategies predicted distress levels. METHODS: UK patients with stage 3 or 4 ovarian cancer were recruited between September 2020 and March 2021. Data were collected at baseline (T0), 2 months (T1), and 4 months (T2) post-enrolment. Validated questionnaires assessed distress (anxiety, depression, PTSD, fear of progression) and predictors (coping strategies and illness perceptions), analysed via multilevel modelling. RESULTS: Seventy-two participants returned a questionnaire at T0, decreasing to 49 by T2. High distress was observed, with over 50% of participants experiencing anxiety and depression consistently. Nearly 60% reported clinical levels of fear of progression at some point. PTSD rates resembled the general population. Although distress levels remained stable over time, some individual variability was observed. Time had minimal effect on distress. Coping strategies and illness perceptions remained stable. Threatening illness perceptions consistently predicted distress, while specific coping strategies such as active coping, acceptance, self-blame, and humour predicted various aspects of distress. Together, these factors explained up to half of the distress variance. CONCLUSION: The findings have implications for routine screening for distress and the inclusion of psychological treatment pathways in advanced ovarian cancer care. Addressing illness representations is crucial, with attention to informational support. Future research should explore the long-term effects of heightened distress and the effectiveness of interventions targeting illness perceptions. This study informs current clinical practice and future pandemic preparedness in cancer care.

British Gynaecological Cancer Society recommendations and guidance on patient-initiated follow-up (PIFU).

The National Cancer Survivorship Initiative through the National Health Service (NHS) improvement in the UK started the implementation of stratified pathways of patient-initiated follow-up (PIFU) across various tumor types. Now the initiative is continued through the Living With and Beyond Cancer program by NHS England. Evidence from non-randomized studies and systematic reviews does not demonstrate a survival advantage to the long-established practice of hospital-based follow-up regimens, traditionally over 5 years. Evidence shows that patient needs are inadequately met under the traditional follow-up programs and there is therefore an urgent need to adapt pathways to the needs of patients. The assumption that hospital-based follow-up is able to detect cancer recurrences early and hence improve patient prognosis has not been validated. A recent survey demonstrates that follow-up practice across the UK varies widely, with telephone follow-up clinics, nurse-led clinics and PIFU becoming increasingly common. There are currently no completed randomized controlled trials in PIFU in gynecological malignancies, although there is a drive towards implementing PIFU. PIFU aims to individualize patient care, based on risk of recurrence and holistic needs, and optimizing resources. The British Gynaecological Cancer Society wishes to provide the gynecological oncology community with guidance and a recommendations statement regarding the value, indications, and limitations of PIFU in endometrial, cervical, ovarian, and vulvar cancers in an effort to standardize practice and improve patient care.

Impact of surgical site infection (SSI) following gynaecological cancer surgery in the UK: a trainee-led multicentre audit and service evaluation.

OBJECTIVES: Surgical site infection (SSI) complicates 5% of all surgical procedures in the UK and is a major cause of postoperative morbidity and a substantial drain on healthcare resources. Little is known about the incidence of SSI and its consequences in women undergoing surgery for gynaecological cancer. Our aim was to perform the first national audit of SSI following gynaecological cancer surgery through the establishment of a UK-wide trainee-led research network. DESIGN AND SETTING: In a prospective audit, we collected data from all women undergoing laparotomy for suspected gynaecological cancer at 12 specialist oncology centres in the UK during an 8-week period in 2015. Clinicopathological data were collected, and wound complications and their sequelae were recorded during the 30 days following surgery. RESULTS: In total, 339 women underwent laparotomy for suspected gynaecological cancer during the study period. A clinical diagnosis of SSI was made in 54 (16%) women. 33% (18/54) of women with SSI had prolonged hospital stays, and 11/37 (29%) had their adjuvant treatment delayed or cancelled. Multivariate analysis found body mass index (BMI) was the strongest risk factor for SSI (OR 1.08[95% CI 1.03 to 1.14] per 1 kg/m2 increase in BMI [p=0.001]). Wound drains (OR 2.92[95% CI 1.41 to 6.04], p=0.004) and staple closure (OR 3.13[95% CI 1.50 to 6.56], p=0.002) were also associated with increased risk of SSI. CONCLUSIONS: SSI is common in women undergoing surgery for gynaecological cancer leading to delays in discharge and adjuvant treatment. Resultant delays in adjuvant treatment may impact cancer-specific survival rates. Modifiable factors, such as choice of wound closure material, offer opportunities for reducing SSI and reducing morbidity in these women. There is a clear need for new trials in SSI prevention in this patient group; our trainee-led initiative provides a platform for their successful completion.

Prevalence of Appendiceal Lesions in Appendicectomies Performed During Surgery for Mucinous Ovarian Tumors: A Retrospective Study.

OBJECTIVES: The aim of this study was to assess the frequency of appendiceal pathology in women undergoing surgery for mucinous ovarian neoplasm and to evaluate whether appendicectomy is necessary. METHODS: This single-institution retrospective study reviewed prevalence of appendiceal lesions in all patients operated on at our institution from 2002 to 2013 with the final diagnosis of mucinous tumor of the ovary. Clinicopathological data were analyzed. RESULTS: One hundred twenty-three cases were identified. These included 45 (37%) benign mucinous ovarian neoplasms, 63 (51%) borderline, and 11 (9%) invasive mucinous ovarian tumors. In addition, 4 (3%) cases of metastatic tumors to the ovary were also identified. Appendiceal pathology was found in association with all types of mucinous ovarian tumors (benign, borderline, and malignant). In 24% of cases, appendix was macroscopically abnormal at the time of the surgery, prompting the surgical removal. Regardless of the gross findings, microscopic abnormality in the appendix was seen in 24% of all cases. The prevalence of significant occult microscopic appendiceal pathology, that is, when the appendix was grossly normal, was 6%. CONCLUSIONS: Given the prevalence of coexisting appendiceal pathology found in this study and the reported low rates of complications associated with the procedure, an appendicectomy is recommended in the management of all mucinous ovarian neoplasms.

Pain relief for women with cervical intraepithelial neoplasia undergoing colposcopy treatment.

BACKGROUND: Pre-cancerous lesions of cervix (cervical intraepithelial neoplasia (CIN)) are usually treated with excisional or ablative procedures. In the UK, the National Health Service (NHS) cervical screening guidelines suggest that over 80% of treatments should be performed in an outpatient setting (colposcopy clinics). Furthermore, these guidelines suggest that analgesia should always be given prior to laser or excisional treatments. Currently various pain relief strategies are employed that may reduce pain during these procedures. OBJECTIVES: To assess whether the administration of pain relief (analgesia) reduces pain during colposcopy treatment and in the postoperative period. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 2), MEDLINE (1950 to March week 3, 2016) and Embase (1980 to week 12, 2016) for studies of any design relating to analgesia for colposcopic management. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared all types of pain relief before, during or after outpatient treatment to the cervix, in women with CIN undergoing loop excision, laser ablation, laser excision or cryosurgery in an outpatient colposcopy clinic setting. DATA COLLECTION AND ANALYSIS: We independently assessed study eligibility, extracted data and assessed risk of bias. We entered data into Review Manager 5 and double checked it for accuracy. Where possible, we expressed results as mean pain score and standard error of the mean with 95% confidence intervals (CI) and synthesised data in a meta-analysis. MAIN RESULTS: We included 19 RCTs (1720 women) of varying methodological quality in the review. These trials compared a variety of interventions aimed at reducing pain in women who underwent treatment for CIN, including cervical injection with lignocaine alone, lignocaine with adrenaline, buffered lignocaine with adrenaline, prilocaine with felypressin, oral analgesics (non-steroidal anti-inflammatory drugs (NSAIDs)), inhalation analgesia (gas mixture of isoflurane and desflurane), lignocaine spray, cocaine spray, local application of benzocaine gel, lignocaine-prilocaine cream (EMLA cream) and transcutaneous electrical nerve stimulation (TENS).Most comparisons were restricted to single trial analyses and were under-powered to detect differences in pain scores between treatments that may or may not have been present. There was no difference in pain relief between women who received local anaesthetic infiltration (lignocaine 2%; administered as a paracervical or direct cervical injection) and a saline placebo (mean difference (MD) -13.74; 95% CI -34.32 to 6.83; 2 trials; 130 women; low quality evidence). However, when local anaesthetic was combined with a vasoconstrictor agent (one trial used lignocaine plus adrenaline while the second trial used prilocaine plus felypressin), there was less pain (on visual analogue scale (VAS)) compared with no treatment (MD -23.73; 95% CI -37.53 to -9.93; 2 trials; 95 women; low quality evidence). Comparing two preparations of local anaesthetic combined with vasoconstrictor, prilocaine plus felypressin did not differ from lignocaine plus adrenaline for its effect on pain control (MD -0.05; 95% CI -0.26 to 0.16; 1 trial; 200 women). Although the mean (± standard deviation (SD)) observed blood loss score was less with lignocaine plus adrenaline (1.33 ± 1.05) compared with prilocaine plus felypressin (1.74 ± 0.98), the difference was not clinically as the overall scores in both groups were low (MD 0.41; 95% CI 0.13 to 0.69; 1 trial; 200 women). Inhalation of gas mixture (isoflurane and desflurane) in addition to standard cervical injection with prilocaine plus felypressin resulted in less pain during the LLETZ (loop excision of the transformation zone) procedure (MD -7.20; 95% CI -12.45 to -1.95; 1 trial; 389 women). Lignocaine plus ornipressin resulted in less measured blood loss (MD -8.75 ml; 95% CI -10.43 to -7.07; 1 trial; 100 women) and a shorter duration of treatment (MD -7.72 minutes; 95% CI -8.49 to -6.95; 1 trial; 100 women) than cervical infiltration with lignocaine alone. Buffered solution (sodium bicarbonate buffer mixed with lignocaine plus adrenaline) was not superior to non-buffered solution of lignocaine plus adrenaline in relieving pain during the procedure (MD -8.00; 95% CI -17.57 to 1.57; 1 trial; 52 women).One meta-analysis found no difference in pain using VAS between women who received oral analgesic and women who received placebo (MD -3.51; 95% CI -10.03 to 3.01; 2 trials; 129 women; low quality evidence).Cocaine spray was associated with less pain (MD -28.00; 95% CI -37.86 to -18.14; 1 trial; 50 women) and blood loss (MD 0.04; 95% CI 0 to 0.70; 1 trial; 50 women) than placebo.None of the trials reported serious adverse events and majority of trials were at moderate or high risk of bias (13 trials). AUTHORS' CONCLUSIONS: Based on two small trials, there was no difference in pain relief in women receiving oral analgesics compared with placebo or no treatment (MD -3.51; 95% CI -10.03 to 3.01; 129 women). We consider this evidence to be of a low to moderate quality. In routine clinical practice, intracervical injection of local anaesthetic with a vasoconstrictor (lignocaine plus adrenaline or prilocaine plus felypressin) appears to be the optimum analgesia for treatment. However, further high quality, adequately powered trials should be undertaken in order to provide the data necessary to estimate the efficacy of oral analgesics, the optimal route of administration and dose of local anaesthetics.

Segregation of ovarian cancer stage exploiting spectral biomarkers derived from blood plasma or serum analysis: ATR-FTIR spectroscopy coupled with variable selection methods.

Ovarian cancer is a solid tumor and a leading cause of mortality. Diagnostic tools for the detection of early stage (stage I) ovarian cancer are urgently needed. For this purpose, attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) coupled with variable selection methods, successive projection algorithm or genetic algorithm (GA) combined with linear discriminant analysis (LDA), were employed to identify spectral biomarkers in blood plasma or serum samples for accurate diagnosis of different stages of ovarian cancer, histological type and segregation based on age. Three spectral datasets (stage I vs. stage II-IV; serous vs. non-serous carcinoma; and, ≤60 years vs. >60 years) were processed: sensitivity and specificity required for real-world diagnosis of ovarian cancer was achieved. Toward segregating stage I vs. stage II-IV, sensitivity and specificity (plasma blood) of 100% was achieved using a GA-LDA model with 33 wavenumbers. For serous vs. non-serous category (plasma blood), the sensitivity and specificity levels, using 29 wavenumbers by GA-LDA, were remarkable (up to 94%). For ≤60 years and >60 years categories (plasma blood), the sensitivity and specificity, using 42 wavenumbers by GA-LDA, gave complete accuracy (100%). For serum samples, sensitivity and specificity results gave relatively high accuracy (up to 91.6% stage I vs. stage II-IV; up to 93.0% serous vs. non-serous; and, up to 96.0% ≤60 years vs. >60 years) using several wavenumbers. These findings justify a prospective population-based assessment of biomarkers signatures using ATR-FTIR spectroscopy as a screening tool for stage of ovarian cancer.

Measuring similarity and improving stability in biomarker identification methods applied to Fourier-transform infrared (FTIR) spectroscopy.

FTIR spectroscopy is a powerful diagnostic tool that can also derive biochemical signatures of a wide range of cellular materials, such as cytology, histology, live cells, and biofluids. However, while classification is a well-established subject, biomarker identification lacks standards and validation of its methods. Validation of biomarker identification methods is difficult because, unlike classification, there is usually no reference biomarker against which to test the biomarkers extracted by a method. In this paper, we propose a framework to assess and improve the stability of biomarkers derived by a method, and to compare biomarkers derived by different method set-ups and between different methods by means of a proposed "biomarkers similarity index".

Vibrational spectroscopy of biofluids for disease screening or diagnosis: translation from the laboratory to a clinical setting.

There remains a need for objective and cost-effective approaches capable of diagnosing early-stage disease in point-of-care clinical settings. Given an increasingly ageing population resulting in a rising prevalence of chronic diseases, the need for screening to facilitate the personalising of therapies to prevent or slow down pathology development will increase. Such a tool needs to be robust but simple enough to be implemented into clinical practice. There is interest in extracting biomarkers from biofluids (e.g., plasma or serum); techniques based on vibrational spectroscopy provide an option. Sample preparation is minimal, techniques involved are relatively low-cost, and data frameworks are available. This review explores the evidence supporting the applicability of vibrational spectroscopy to generate spectral biomarkers of disease in biofluids. We extend the inter-disciplinary nature of this approach to hypothesise a microfluidic platform that could allow such measurements. With an appropriate lightsource, such engineering could revolutionize screening in the 21(st) century.

Histology verification demonstrates that biospectroscopy analysis of cervical cytology identifies underlying disease more accurately than conventional screening: removing the confounder of discordance.

BACKGROUND: Subjective visual assessment of cervical cytology is flawed, and this can manifest itself by inter- and intra-observer variability resulting ultimately in the degree of discordance in the grading categorisation of samples in screening vs. representative histology. Biospectroscopy methods have been suggested as sensor-based tools that can deliver objective assessments of cytology. However, studies to date have been apparently flawed by a corresponding lack of diagnostic efficiency when samples have previously been classed using cytology screening. This raises the question as to whether categorisation of cervical cytology based on imperfect conventional screening reduces the diagnostic accuracy of biospectroscopy approaches; are these latter methods more accurate and diagnose underlying disease? The purpose of this study was to compare the objective accuracy of infrared (IR) spectroscopy of cervical cytology samples using conventional cytology vs. histology-based categorisation. METHODS: Within a typical clinical setting, a total of n = 322 liquid-based cytology samples were collected immediately before biopsy. Of these, it was possible to acquire subsequent histology for n = 154. Cytology samples were categorised according to conventional screening methods and subsequently interrogated employing attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy. IR spectra were pre-processed and analysed using linear discriminant analysis. Dunn's test was applied to identify the differences in spectra. Within the diagnostic categories, histology allowed us to determine the comparative efficiency of conventional screening vs. biospectroscopy to correctly identify either true atypia or underlying disease. RESULTS: Conventional cytology-based screening results in poor sensitivity and specificity. IR spectra derived from cervical cytology do not appear to discriminate in a diagnostic fashion when categories were based on conventional screening. Scores plots of IR spectra exhibit marked crossover of spectral points between different cytological categories. Although, significant differences between spectral bands in different categories are noted, crossover samples point to the potential for poor specificity and hampers the development of biospectroscopy as a diagnostic tool. However, when histology-based categories are used to conduct analyses, the scores plot of IR spectra exhibit markedly better segregation. CONCLUSIONS: Histology demonstrates that ATR-FTIR spectroscopy of liquid-based cytology identifies the presence of underlying atypia or disease missed in conventional cytology screening. This study points to an urgent need for a future biospectroscopy study where categories are based on such histology. It will allow for the validation of this approach as a screening tool.

Vibrational biospectroscopy coupled with multivariate analysis extracts potentially diagnostic features in blood plasma/serum of ovarian cancer patients.

Despite numerous advances in "omics" research, early detection of ovarian cancer still remains a challenge. The aim of this study was to determine whether attenuated total reflection Fourier-transform infrared (ATR-FTIR) or Raman spectroscopy could characterise alterations in the biomolecular signatures of human blood plasma/serum obtained from ovarian cancer patients compared to non-cancer controls. Blood samples isolated from ovarian cancer patients (n = 30) and healthy controls (n = 30) were analysed using ATR-FTIR spectroscopy. For comparison, a smaller cohort of samples (n = 8) were analysed using an InVia Renishaw Raman spectrometer. Resultant spectra were pre-processed prior to being inputted into principal component analysis (PCA) and linear discriminant analysis (LDA). Statistically significant differences (P < 0.001) were observed between spectra of ovarian cancer versus control subjects for both biospectroscopy methods. Using a support vector machine classifier for Raman spectra of blood plasma, a diagnostic accuracy of 74% was achieved, while the same classifier showed 93.3% accuracy for IR spectra of blood plasma. These observations suggest that a biospectroscopy approach could be applied to identify spectral alterations associated with the presence of insidious ovarian cancer.

Exploiting biospectroscopy as a novel screening tool for cervical cancer: towards a framework to validate its accuracy in a routine clinical setting.

Biospectroscopy is an emerging field that harnesses the platform of physical sciences with computational analysis in order to shed novel insights on biological questions. An area where this approach seems to have potential is in screening or diagnostic clinical settings, where there is an urgent need for new approaches to objectively interrogate large numbers of samples in an objective fashion with acceptable levels of sensitivity and specificity. This review outlines the benefits of biospectroscopy in screening for precancer lesions of the cervix due to its ability to separate different grades of dysplasia. It evaluates the feasibility of introducing this technique into cervical screening programs on the basis of its ability to identify biomarkers of progression within derived spectra ('biochemical­cell fingerprints').

Surgical approach to a vulval-pubic cartilaginous cyst: A case report and review of published work.

Cartilaginous cyst of symphysis pubis is rare and to our knowledge 12 cases have been reported in the published work. Although cartilaginous cysts of the vulva and pubis are likely to present to a gynecologist as a vulval-pubic mass, their diagnosis and management warrants a multidisciplinary team approach because of their rarity and anatomical location. Non-invasive diagnosis includes magnetic resonance imaging and ultrasound scan, while the invasive preoperative biopsy is reserved for cases with a high index of suspicion of malignancy. The surgical approach for the management of vulval-pubic cartilaginous cyst is not well established. The current case demonstrates a joint surgical approach involving a gynecologist and orthopedic surgeon in management of a degenerative cartilaginous cyst. As this condition is benign, every effort should be made to preserve the stability of the pubic symphysis. Symphyseal dysfunction from surgery remains a potential complication for which treatment is not straightforward.

Fourier-transform infrared spectroscopy coupled with a classification machine for the analysis of blood plasma or serum: a novel diagnostic approach for ovarian cancer.

Currently available screening tests do not deliver the required sensitivity and specificity for accurate diagnosis of ovarian or endometrial cancer. Infrared (IR) spectroscopy of blood plasma or serum is a rapid, versatile, and relatively non-invasive approach which could characterize biomolecular alterations due to cancer and has potential to be utilized as a screening or diagnostic tool. In the past, no such approach has been investigated for its applicability in screening and/or diagnosis of gynaecological cancers. We set out to determine whether attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy coupled with a proposed classification machine could be applied to IR spectra obtained from plasma and serum for accurate class prediction (cancer vs. normal). Plasma and serum samples were obtained from ovarian cancer cases (n = 30), endometrial cancer cases (n = 30) and non-cancer controls (n = 30), and subjected to ATR-FTIR spectroscopy. Four derived datasets were processed to estimate the real-world diagnosis of ovarian and endometrial cancer. Classification results for ovarian cancer were remarkable (up to 96.7%), whereas endometrial cancer was classified with a relatively high accuracy (up to 81.7%). The results from different combinations of feature extraction and classification methods, and also classifier ensembles, were compared. No single classification system performed best for all different datasets. This demonstrates the need for a framework that can accommodate a diverse set of analytical methods in order to be adaptable to different datasets. This pilot study suggests that ATR-FTIR spectroscopy of blood is a robust tool for accurate diagnosis, and carries the potential to be utilized as a screening test for ovarian cancer in primary care settings. The proposed classification machine is a powerful tool which could be applied to classify the vibrational spectroscopy data of different biological systems (e.g., tissue, urine, saliva), with their potential application in clinical practice.

Pain relief for women with cervical intraepithelial neoplasia undergoing colposcopy treatment.

BACKGROUND: Pre-cancerous lesions of cervix (cervical intraepithelial neoplasia (CIN)) are usually treated with excisional or ablative procedures. In the UK, the NHS cervical screening guidelines suggest that over 80% of treatments should be performed in an outpatient setting (colposcopy clinics). Furthermore, these guidelines suggest that analgesia should always be given prior to laser or excisional treatments. Currently various pain relief strategies are employed that may reduce pain during these procedures. OBJECTIVES: The aim of this review was to assess whether the administration of pain relief reduced pain during colposcopy treatment and in the postoperative period. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Review Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL - May 2011) (2011, Issue 2), MEDLINE (1950 to May week 2, 2011), EMBASE (1980 to week 20, 2011) for studies of any design relating to analgesia for colposcopic management. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared all types of pain relief before, during or after outpatient treatment to the cervix, in adult women with CIN undergoing loop excision, laser ablation, laser excision or cryosurgery in an outpatient colposcopy clinic setting. DATA COLLECTION AND ANALYSIS: We independently assessed study eligibility, extracted data and assessed risk of bias. We entered data into RevMan and double checked it for accuracy. Where possible, the results were expressed as mean pain score and standard error of the mean with 95% confidence intervals (CI) and the data were synthesised in a meta-analysis. MAIN RESULTS: We included 17 RCTs (1567 women) of varying methodological quality in the review. These trials compared a variety of interventions aimed at reducing pain in women who underwent treatment for CIN, including cervical injection with lignocaine alone, lignocaine with adrenaline, prilocaine with felypressin, oral analgesics (non-steroidal anti-inflammatory drugs (NSAIDs)), inhalation analgesia (gas mixture of isoflurane and desflurane), lignocaine spray, cocaine spray, local application of benzocaine gel, lignocaine-prilocaine cream (EMLA cream) and transcutaneous electrical nerve stimulation (TENS).Most comparisons were restricted to single trial analyses and were under-powered to detect differences in pain scores between treatments that may or may not have been present. There was no significant difference in pain relief between women who received local anaesthetic infiltration (lignocaine 2%; administered as a paracervical or direct cervical injection) and a saline placebo (2 trials; 130 women; MD -13.74; 95% CI -34.32 to 6.83). However, when local anaesthetic was combined with a vasoconstrictor agent (one trial used lignocaine combined with adrenaline while the second trial used prilocaine combined with felypressin), significantly less pain (on visual analogue scores) occurred compared with no treatment (2 trials; 95 women; MD -23.73; 95% CI -37.53 to -9.93). Comparing two preparations of local anaesthetic plus vasoconstrictor, prilocaine combined with felypressin did not differ from lignocaine combined with adrenaline for its effect on pain control (1 trial; 200 women; MD -0.05; 95% CI -0.26 to 0.16). Although the mean observed blood loss score was less with lignocaine plus adrenaline (1.33 ± 1.05) as compared with prilocaine plus felypressin (1.74 ± 0.98), the difference was not clinically significant as the overall scores in both groups were low (1 trial; 200 women; MD 0.41; 95% CI 0.13 to 0.69). Inhalation of gas mixture (isoflurane and desflurane) in addition to standard cervical injection with prilocaine plus felypressin resulted in significantly less pain during the LLETZ (loop excision of the transformation zone) procedure (1 trial; 389 women; MD -7.20; 95% CI -12.45 to -1.95). Lignocaine plus ornipressin resulted in significantly less measured blood loss (1 trial; 100 women; MD -8.75; 95% CI -10.43 to -7.07) and a shorter duration of treatment (1 trial; 100 women; MD -7.72; 95% CI -8.49 to -6.95) than cervical infiltration with lignocaine alone.One meta-analysis found no statistically significant difference in pain using visual analogue scores between women who received oral analgesic and those who received placebo (2 trials; 129 women; MD -3.51; 95% CI -10.03 to 3.01; Analysis 6.1).Cocaine spray was associated with significantly less pain (1 trial; 50 women; MD -28; 95% CI -37.86 to -18.14) and blood loss (1 trial; 50 women; MD 0.04; 95% CI 0 to 0.70) than placebo.No serious adverse events were reported in any of the trials and majority of trials were at moderate or high risk of bias (n = 12). AUTHORS' CONCLUSIONS: Based on two small trials, there was no significant difference in pain relief in women receiving oral analgesics compared with placebo or no treatment (129 women; MD -3.51; 95% CI -10.03 to 3.01). We consider this evidence to be of a low to moderate quality. In routine clinical practice, intracervical injection of local anaesthetic with a vasoconstrictor (lignocaine plus adrenaline or prilocaine plus felypressin) appears to be the optimum analgesia for treatment. However, further high-quality, adequately powered trials should be undertaken in order to provide the data necessary to estimate the efficacy of oral analgesics, the optimal route of administration and dose of local anaesthetics.

Cytochrome P1B1 (CYP1B1) polymorphisms and ovarian cancer risk: a meta-analysis.

CYP1B1 is a key P450 enzyme involved in the metabolism of exogenous and endogenous substrates and plays a key role in hormone-induced carcinogenesis. Risk factors for ovarian cancer are related to hormonal exposure and reproduction, and polymorphisms within genes involved in metabolism of oestrogen and certain xenobiotics may influence the risk of developing ovarian cancer. Current meta-analysis evaluated four CYP1B1 polymorphisms (Leu432Val, Arg48Gly, Ala119Ser and Asn453Ser) for their association with ovarian cancer risk. A search of the MEDLINE bibliographic database for the period up to April 2012 identified five relevant studies. With regards to Leu432Val polymorphism, all of the five studies were eligible (1199 cases and 2596 controls) for analysis, while for Arg48Gly (799 cases and 1169 controls), Ala119Ser (799 cases and 1172 controls) and Asn453Ser (361cases and 1577 controls) only two studies were eligible for analysis. Fixed-effect models were used to estimate pooled odds ratios (OR) with 95% confidence intervals (95% CI) and chi-square based Q-test was used to test for heterogeneity. The pooled OR (95% CI) for CYP1B1_Leu432Val polymorphism were 1.1 (0.84-1.31) for heterozygous subjects and 0.82 (0.57-1.17) for homozygous Val subjects. In a recessive model, homozygous carriers of Leu432Val showed a weak trend towards reduced risk as compared to 'wild type' and heterozygous carriers (OR 0.8, 95% CI; 0.66-0.99); however, this association was of limited significance. Regarding Arg48Gly, the pooled OR (95% CI) were 1.06 (0.89-1.27) for heterozygous and 0.98 (1.72-1.33) for homozygous Gly subjects. With respect to Ala119Ser and Asn453Ser, the pooled OR were 1.06 (0.87-1.29) and 1.24 (0.94-1.63) for heterozygous and 1.1 (0.8-1.52) and 1.09 (0.5-2.34) for homozygous respectively. In conclusion, this meta-analysis suggests that CYP1B1 polymorphisms are not associated with ovarian cancer risk. Studies evaluating CYP1B1_Leu432Val polymorphism are required to further elucidate the risk of ovarian cancer with this polymorphism. Additionally, studies amongst Asian and African subjects are required to estimate race-specific effects.