Objectives
Assessment of empirical diffusion-weighted MRI (DW-MRI) models in cervical tumours to investigate whether fitted parameters distinguish between types and grades of tumours.
Methods
...Forty-two patients (24 squamous cell carcinomas, 14 well/moderately differentiated, 10 poorly differentiated; 15 adenocarcinomas, 13 well/moderately differentiated, two poorly differentiated; three rare types) were imaged at 3 T using nine b-values (0 to 800 s mm
-2
). Mono-exponential, stretched exponential, kurtosis, statistical, and bi-exponential models were fitted. Model preference was assessed using Bayesian Information Criterion analysis. Differences in fitted parameters between tumour types/grades and correlation between fitted parameters were assessed using two-way analysis of variance and Pearson's linear correlation coefficient, respectively.
Results
Non-mono-exponential models were preferred by 83 % of tumours with bi-exponential and stretched exponential models preferred by the largest numbers of tumours. Apparent diffusion coefficient (ADC) and diffusion coefficients from non-mono-exponential models were significantly lower in poorly differentiated tumours than well/moderately differentiated tumours. α (stretched exponential), K (kurtosis),
f
and D* (bi-exponential) were significantly different between tumour types. Strong correlation was observed between ADC and diffusion coefficients from other models.
Conclusions
Non-mono-exponential models were preferred to the mono-exponential model in DW-MRI data from cervical tumours. Parameters of non-mono-exponential models showed significant differences between types and grades of tumours.
Key Points
•
Non-mono-exponential DW-MRI models are preferred in the majority of cervical tumours
.
•
Poorly differentiated cervical tumours exhibit lower diffusion coefficients than well/moderately differentiated tumours
.
•
Non-mono-exponential model parameters α, K, f, and D* differ between tumour types
.
•
Micro-structural features are likely to affect parameters in non-mono-exponential models differently
.
Cervical cancer affects over half a million people worldwide each year, the majority of whom are in resource-limited settings where cytology screening is not available. As persistent human papilloma ...virus (HPV) infections are a key causative factor, detection of HPV strains now complements cytology where screening services exist. This work demonstrates the efficacy of a handheld Lab-on-Chip (LoC) device, with an external sample extraction process, in detecting cervical cancer from biopsy samples. The device is based on Ion-Sensitive Field-Effect Transistor (ISFET) sensors used in combination with loop-mediated isothermal amplification (LAMP) assays, to amplify HPV DNA and human telomerase reverse transcriptase (hTERT) mRNA. These markers were selected because of their high levels of expression in cervical cancer cells, but low to nil expression in normal cervical tissue. The achieved analytical sensitivity for the molecular targets resolved down to a single copy per reaction for the mRNA markers, achieving a limit of detection of 10
for hTERT. In the tissue samples, HPV-16 DNA was present in 4/5 malignant and 2/5 benign tissues, with HPV-18 DNA being present in 1/5 malignant and 1/5 benign tissues. hTERT mRNA was detected in all malignant and no benign tissues, with the demonstrated pilot data to indicate the potential for using the LoC in cervical cancer screening in resource-limited settings on a large scale.
The use of robotic-assisted keyhole surgery in gynaecology has expanded in recent years owing to technical advances. These include 3D viewing leading to improved depth perception, limitation of ...tremor, potential for greater precision and discrimination of tissues, a shorter learning curve and improved comfort for surgeons compared with conventional keyhole and open abdominal surgery. Robotic-assisted keyhole surgery, compared with conventional keyhole surgery, improves surgical performance without increasing operating time, minimises blood loss and intra- or postoperative complications, while reducing the need to revert to abdominal surgery. Moreover, surgeons using a robot experience fewer skeletomuscular problems of their own in the short and long term than those operating without a robot as an additional tool. This Scientific Impact Paper looks at the use of a robot in different fields of gynaecological surgery. A robot could be considered safe and a more effective surgical tool than conventional keyhole surgery for women who have to undergo complex gynaecology surgery or have associated medical issues such as body-mass index (BMI) at 30 kg/m
or above or lung problems. The introduction of the use of robots in keyhole surgery has resulted in a decrease in the number of traditional open surgeries and the risk of conversion to open surgery after traditional keyhole surgery; both of which should be considered when examining the cost-benefit of using a robot. Limitations of robotic-assisted surgery remain the associated higher costs. In womb cancer surgery there is good evidence that introducing robotics into the service improves outcomes for women and may reduce costs.
Objective
To compare sensitivity and specificity of endovaginal versus external-array coil T2-W and T2-W + DWI for detecting and staging small cervical tumours.
Methods
Optimised endovaginal and ...external array coil MRI at 3.0-T was done prospectively in 48 consecutive patients with stage Ia/Ib1 cervical cancer. Sensitivity/specificity for detecting tumour and parametrial extension against histopathology for a reading radiologist were determined on coronal T2-W and T2W + DW images. An independent radiologist also scored T2-W images without and with addition of DWI for the external-array and endovaginal coils on separate occasions >2 weeks apart. Cohen’s kappa assessed inter- and intra-observer agreement.
Results
Median tumour volume in 19/38 cases positive on subsequent histology was 1.75 cm
3
. Sensitivity, specificity, PPV, NPV were: reading radiologist 91.3 %, 89.5 %, 91.3 %, 89.5 %, respectively; independent radiologist T2-W 82.6 %, 73.7 %, 79.1 %, 77.8 % for endovaginal, 73.9 %, 89.5 %, 89.5 %, 73.9 % for external-array coil. Adding DWI improved sensitivity and specificity of endovaginal imaging (78.2 %, 89.5 %); adding DWI to external-array imaging improved specificity (94.7 %) but reduced sensitivity (66.7 %). Inter- and intra-observer agreement on T2-W + DWI was good (kappa = 0.67 and 0.62, respectively).
Conclusion
Endovaginal coil T2-W MRI is more sensitive than external-array coil for detecting tumours <2 cm
3
; adding DWI improves specificity of endovaginal imaging but reduces sensitivity of external-array imaging.
Key Points
•
Endovaginal more accurate than external-array T2-W MRI for detecting small cervical cancers.
•
Addition of DWI improves sensitivity and specificity of endovaginal T2-W imaging.
•
Addition of DWI substantially reduces sensitivity of external-array T2-W imaging.
To establish the sensitivity and specificity of a human papillomavirus (HPV) and tumor marker DNA/mRNA assay for detecting cervical cancer that is transferrable to a Lab-on-a-chip platform and ...determine its diagnostic benefit in early stage disease when used in conjunction with high-resolution endovaginal magnetic resonance imaging (MRI).
Forty-one patients (27 with Stage1 cervical cancer Group1 and 14 non-cancer HPV negative controls Group2) had DNA and RNA extracted from cervical cytology swab samples. HPV16, HPV18, hTERT, TERC/GAPDH and MYC/GAPDH concentration was established using a loop mediated isothermal amplification (LAMP) assay. Thresholds for tumor marker detection for Group1 were set from Group2 analysis (any hTERT, TERC/GAPDH 3.12, MYC/GAPDH 0.155). Group 1 participants underwent endovaginal MRI. Sensitivity and specificity for cancer detection by LAMP and MRI individually and combined was documented by comparison to pathology.
Sensitivity and specificity for cancer detection was 68.8% and 77.8% if any tumor marker was positive regardless of HPV status (scenario1), and 93.8% and 55.8% if tumor marker or HPV were positive (scenario 2). Adding endovaginal MRI improved specificity to 88.9% in scenario 1 (sensitivity 68.8%) and to 77.8%% in scenario2 (sensitivity 93.8%).
Specificity for cervical cancer detection using a LAMP assay is superior with tumor markers; low sensitivity is improved by HPV detection. Accuracy for early stage cervical cancer detection is optimal using a spatially multiplexed tumor marker/HPV LAMP assay together with endovaginal MRI.
This study aimed to determine the frequency of malignant pathology in a macroscopically normal appendix during surgery for a borderline or malignant mucinous ovarian tumor (MOT).
Women with ...borderline and malignant MOT were identified from the pathology database from 2000 to 2014. Women who had a benign MOT and had an appendicectomy were excluded from the study. Data were collected from the electronic patient record and case notes.
Of 310 women identified with MOT, 203 patients with benign MOT were excluded. Of the remaining 107 patients, 15 patients with previous appendicectomy were also excluded. The study population consisted of 92 patients. There were 57 (62%) patients with borderline MOT and 35 (38%) patients with malignant MOT. In the borderline subgroup, 40/57 (70%) patients had appendicectomy of whom 8 (20%) had macroscopically abnormal appendices. One patient had pseudomyxoma peritonei secondarily involving the appendix and 7 patients had a histologically normal appendix. Normal histology was found in all macroscopically normal appendices. In the malignant subgroup, 29/35 (83%) patients had an appendicectomy. There were 8 (27.5%) macroscopically abnormal appendices with a malignant pathology in 7 (87.5%) patients and 1 patient had a resolving appendicitis. There were 21 macroscopically normal appendices of which, serrated adenoma was found in 1 (4.8%) patient, whereas the remaining 20 (95.2%) patients had normal histology.
In MOT, an abnormal appearing appendix should be excised. If the appendix is grossly normal, our data do not support performing an appendicectomy as part of a surgical staging procedure.
Textural features extracted from MRI potentially provide prognostic information additional to volume for influencing surgical management of cervical cancer.
To identify textural features that differ ...between cervical tumors above and below the volume threshold of eligibility for trachelectomy and determine their value in predicting recurrence in patients with low-volume tumors.
Of 378 patients with Stage1–2 cervical cancer imaged prospectively (3T, endovaginal coil), 125 had well-defined, histologically-confirmed squamous or adenocarcinomas with >100 voxels (>0.07 cm3) suitable for radiomic analysis. Regions-of-interest outlined the whole tumor on T2-W images and apparent diffusion coefficient (ADC) maps. Textural features based on grey-level co-occurrence matrices were compared (Mann-Whitney test with Bonferroni correction) between tumors greater (n = 46) or less (n = 79) than 4.19 cm3. Clustering eliminated correlated variables. Significantly different features were used to predict recurrence (regression modelling) in surgically-treated patients with low-volume tumors and compared with a model using clinico-pathological features.
Textural features (Dissimilarity, Energy, ClusterProminence, ClusterShade, InverseVariance, Autocorrelation) in 6 of 10 clusters from T2-W and ADC data differed between high-volume (mean ± SD 15.3 ± 11.7 cm3) and low-volume (mean ± SD 1.3 ± 1.2 cm3) tumors. (p < 0.02). In low-volume tumors, predicting recurrence was indicated by: Dissimilarity, Energy (ADC-radiomics, AUC = 0.864); Dissimilarity, ClusterProminence, InverseVariance (T2-W-radiomics, AUC = 0.808); Volume, Depth of Invasion, LymphoVascular Space Invasion (clinico-pathological features, AUC = 0.794). Combining ADC-radiomic (but not T2-radiomic) and clinico-pathological features improved prediction of recurrence compared to the clinico-pathological model (AUC = 0.916, p = 0.006). Findings were supported by bootstrap re-sampling (n = 1000).
Textural features from ADC maps and T2-W images differ between high- and low-volume tumors and potentially predict recurrence in low-volume tumors.
•Texture features differed significantly between high-compared to low-volume cervical tumors (p < 0.02).•In low-volume tumors predicting recurrence from ADC-radiomics was superior to T2W-radiomics or clinico-pathologic features.•Combining ADC-radiomics and clinico-pathologic features together improved recurrence prediction further.
Abstract Objectives To determine the impact on survival of symptomatic and asymptomatic venous thromboembolism (VTE) at time of diagnosis of primary ovarian malignancy. Materials and methods The ...clinical records of 397 consecutive cases of primary ovarian malignancy were studied. Clinical, pathological and survival data were obtained. Results and conclusions Of 397 cases, 19 (4.8%) were found to have VTE at diagnosis, of which 63.2% (n = 12) were asymptomatic. VTE was significantly associated with reduced overall median survival (28 vs. 45 months, p = 0.004). Decreased survival was associated with symptomatic VTE compared to patients with asymptomatic VTE (21 vs. 36 months, p = 0.02) whose survival was similar to that of patients without VTE. Decreased survival remained significant in symptomatic patients after controlling for stage of disease at diagnosis, cytoreductive status and adjuvant chemotherapy use. Overall these data suggest for the first time that symptomatic but not asymptomatic VTE prior to primary treatment of ovarian cancer is an independent adverse prognostic factor.
Abstract Aim The aim of this study is to validate high-resolution endovaginal T2- and diffusion-weighted MRI measurements (tumour size, volume and length of uninvolved cervical canal) against ...histology in patients undergoing trachelectomy. Patients/interventions 55 consecutive patients 25–44 years with cervical cancer being considered for trachelectomy were prospectively assessed with endovaginal T2-W and diffusion-weighted MRI. Two independent observers blinded to histology recorded maximum tumour dimension, volume and distance from the superior aspect of the tumour to the internal os. Following trachelectomy, pathologist-outlined tumour sections were photographed with a set scale and similar measurements were recorded. Results Fifteen of 45 patients subsequently treated with fertility-sparing surgery had residual tumour (median histological volume: 0.28 cm3 , IQR = 0.14–1.06 cm3 ). Sensitivity, specificity, positive and negative predictive values for detecting tumour: Observer1: 86.7%, 80.0%, 68.4%, and 92.3%, respectively; Observer2: 86.7%, 90.0%, 81.0%, and 93.1%, respectively. Size and volume correlated between observers (r = 0.96, 0.84, respectively, p < 0.0001). Size correlated between each observer and histology (observer 1 r = 0.91, p < 0.0001; observer 2 r = 0.93, p < 0.0001), volume did not (observer 1: r = 0.08, p = 0.6; observer 2: r = 0.21, p = 0.16); however, differences between observer measurements and histology were not significant (size p = 0.09, volume p = 0.15). Differences between MRI and histology estimates of endocervical canal length were not significant (p = 0.1 both observers). Conclusion In subcentimetre cervical cancers, endovaginal MRI correlates with pathology and is invaluable in assessing patients for fertility-sparing surgery.
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