Mohammed Keshtgar’s research while affiliated with Royal Free London NHS Foundation Trust and other places

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Publications (114)


Impact of post mastectomy radiotherapy on the silicone breast implant
  • Article

December 2018

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54 Reads

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8 Citations

Materials Science and Engineering C

Louise J. Magill

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Kate Ricketts

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Mohammed Keshtgar

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[...]

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Gavin Jell

Implant based reconstruction accounts for over half of breast reconstruction performed in the UK. Patients with implant based breast reconstructions undergoing post mastectomy radiotherapy are at increased risk of capsular contracture and reconstructive failure. This study sought to determine the effect of treatment dose radiotherapy on the bulk mechanical, surface chemical properties of silicone implants as well as their cellular response. Silicone breast implant shells were submitted to treatment dose radiotherapy, 2.67 Gy (one daily fraction) and 40.05 Gy (15 fractions) using non-irradiated shells as controls. Bulk mechanical and surface chemical properties of the shells were evaluated using tensile and tear testing, attenuated total reflectance – fourier transform infrared spectroscopy (ATR-FTIR), water contact angle measurements. HDFa cells were seeded on the shells and Alamar Blue assay was performed to study cell metabolic activity. Cell morphology was evaluated using phalloidin and DAPI staining. There was no significant difference in tensile, tear strength and Young's modulus however there was reduction in maximum elongation following irradiation. Irradiation of the shells did not significant alter spectroscopy measurements nor wettability of the shells. Cell metabolism was not significantly affected by irradiation. Further analysis is warranted of the micromechanical properties to fully elucidate the effect of irradiation on the breast implant which could explain the increased rate of capsular contracture and reconstructive failure in patients undergoing post-mastectomy radiotherapy.


Mechanical and Surface Chemical Analysis of Retrieved Breast Implants from a Single Centre

November 2018

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34 Reads

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13 Citations

Journal of the Mechanical Behavior of Biomedical Materials

Introduction: Breast implants are associated with complications such as capsular contracture, implant rupture and leakage often necessitating further corrective surgery. Re-operation rates have been reported to occur in up to 15.4% of primary augmentation patients and up to 27% in primary reconstructions patients within the first three years (Cunningham, 2007). The aim of this study was to examine the mechanical and surface chemical properties as well as the fibroblast response of retrieved breast implants in our unit to determine the in vivo changes which occur over time. Methods: Ethical approval was obtained. 47 implants were retrieved. Implantation time ranged from 1 month to 388 months (Mean 106.1 months). Tensile strength, elongation, Young's modulus and tear strength properties were measured using Instron 5565 tensiometer on anterior and posterior aspects of the implant. Attenuated total reflectance-fourier transform infra-red spectroscopy (ATR-FTIR), wettability and scanning electron microscopy (SEM) analysis was performed on the shell surfaces. Bicinchoninic acid assay was performed to determine shell protein content. The fibroblast response was determined by seeding HDFa cells on the retrieved implants and cell metabolism measured using Alamar Blue™ assay. Results: Mechanical properties fall with increasing duration of implantation. There were no significant changes in ATR-FTIR spectra between ruptured and intact implants nor significant changes in wettability in implants grouped into 5 year categories. SEM imaging reveals surface degradation changes with increasing duration of implantation. Conclusions: With increasing duration of implantation, mechanical properties of the breast implants fall. However this was not associated with surface chemical changes as determined by ATR-FTIR and wettability nor protein content of the shells. Thus the reduction in mechanical properties is associated with breast implant failure but further research is required to elucidate the mechanisms.


Figure 1 -2D images (face and lateral views) for subjective evaluation -Software for experts with 2D case display of all views and classification online
Figure 2 -Microsoft Kinect captured images
Figure 4 b -Weighted Kappa Mean, Min, Max and Standard Deviation (SD) values -Comparison between panel evaluation with 2D and 3D images, individually and with the consensual classification. Single value for comparison between consensus classification 2D and the BCCT.core and BCCT.core3D
The value of 3D images in the aesthetic evaluation of breast cancer conservative treatment. Results from a prospective multicentric clinical trial
  • Article
  • Full-text available

June 2018

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225 Reads

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9 Citations

The Breast

Purpose: BCCT.core (Breast Cancer Conservative Treatment. cosmetic results) is a software created for the objective evaluation of aesthetic result of breast cancer conservative treatment using a single patient frontal photography. The lack of volume information has been one criticism, as the use of 3D information might improve accuracy in aesthetic evaluation. In this study, we have evaluated the added value of 3D information to two methods of aesthetic evaluation: a panel of experts; and an augmented version of the computational model - BCCT.core3d. Material and methods: Within the scope of EU Seventh Framework Programme Project PICTURE, 2D and 3D images from 106 patients from three clinical centres were evaluated by a panel of 17 experts and the BCCT.core. Agreement between all methods was calculated using the kappa (K) and weighted kappa (wK) statistics. Results: Subjective agreement between 2D and 3D individual evaluation was fair to moderate. The agreement between the expert classification and the BCCT.core software with both 2D and 3D features was also fair to moderate. Conclusions: The inclusion of 3D images did not add significant information to the aesthetic evaluation either by the panel or the software. Evaluation of aesthetic outcome can be performed using of the BCCT.core software, with a single frontal image.

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CONSORT diagram
Cosmesis Outcomes (% Excellent-Good) by Rater. 95% Confidence Intervals displayed are the upper limits for the TARGIT-IORT group and the lower limits for the EBRT group
Cosmesis Outcomes (% Excellent-Good) by Treatment
Cosmetic outcome as rated by patients, doctors, nurses and BCCT.core software assessed over 5 years in a subset of patients in the TARGIT-A Trial

April 2018

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97 Reads

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39 Citations

Radiation Oncology

Background: The purpose of this research was to assess agreement between four rating systems of cosmetic outcome measured in a subset of patients with early breast cancer participating in the randomised TARGIT-A trial. TARGIT-A compared risk-adapted single-dose intra-operative radiotherapy (TARGIT-IORT) to whole breast external beam radiotherapy (EBRT). Methods: Patients, their Radiation Oncologist and Research Nurse completed a subjective cosmetic assessment questionnaire before radiotherapy and annually thereafter for five years. Objective data previously calculated by the validated BCCT.core software which utilizes digital photographs to score symmetry, colour and scar was also used. Agreement was assessed by the Kappa statistic and longitudinal changes were assessed by generalized estimating equations. Results: Overall, an Excellent-Good (EG) cosmetic result was scored more often than a Fair-Poor (FP) result for both treatment groups across all time points, with patients who received TARGIT-IORT scoring EG more often than those who received EBRT however this was statistically significant at Year 5 only. There was modest agreement between the four rating systems with the highest Kappa score being moderate agreement which was between nurse and doctor scores at Year 1 with Kappa = 0.46 (p < 0.001), 95% CI (0.24, 0.68). Conclusion: Despite similar overall findings between treatment groups and rating systems, the inter-rater agreement was only modest. This suggests that the four rating systems utilized may not necessarily be used interchangeably and it is arguable that for an outcome such as cosmetic appearance, the patient's point of view is the most important. Trial registration: TARGIT-A ISRCTN34086741 , Registered 21 July 2004, retrospectively registered.


Electrochemotherapy for Breast Cancer – results from the INSPECT database

March 2018

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98 Reads

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39 Citations

Clinical Breast Cancer

Background Cutaneous recurrence from breast cancer can pose a clinical challenge. It might be the only disease site, or could be part of disseminated disease, and often profoundly impacts quality of life. Electrochemotherapy is a palliative treatment using electric pulses to locally permeabilise tumour cells and thereby increase bleomycin cytotoxicity significantly. Collaborating with the International Network for sharing Practice on ElectroChemoTherapy (INSPECT), we consecutively and prospectively accrued data on patients treated with electrochemotherapy for cutaneous metastases from breast cancer. Methods Patients were treated with electrochemotherapy at ten European centers. Under either local or general anaesthesia patients were treated with either local injection (1000 IU/ml intratumoural) or systemic infusion (15,000 IU/m2) of bleomycin. Results 119 patients were included at ten institutions in the INSPECT network. Primary location was the chest (89%), median diameter of the cutaneous metastases being 25mm. 90 patients were available for response evaluation after 2 months. Complete response was observed in 45 (50%) patients, partial response in 19 (21%), stable disease in 16 (18%), and progressive disease in 7 (8%). 3 patients were not evaluable. Common side effects were ulceration, long-lasting hyperpigmentation, and low grade pain. No serious adverse events were observed. Conclusion Electrochemotherapy showed high response rates after a single treatment. Electrochemotehrapy has few side effects and can be used as an adjunct to systemic therapies or as a solo treatment. We therefore recommend considering electrochemotherapy for patients with cutaneous metastases.


Fig. 2. Pose error profile in synthetic data experiment. The figure shows the quantified translational and rotational error plotted against estimated camera poses. 
Fig. 3. Surface-to-surface error distributions horizontally grouped into syntethic, Kinect v1 and v2 results. The bars on the left correspond to mean surface distances, the bars on the right to mean surface normal deviation. 
Fig. 4. Qualitative results in frontal view. Left to right: Synthetic, Kinect v1 and v2 reconstructions for the same patient, phantom reconstructions and two patients of different cup size. Texture, where available, is partly blended onto geometry. 
Fig. 5. Colourmapped surface-to-surface distance to the left of surface normal deviation for all methods excluding VisualSfM. We display the data sets with the smallest and largest average distance error alongside real patient results with visible artefacts such as the movement of hands leading to gross errors.
A Comparative Study of Breast Surface Reconstruction for Aesthetic Outcome Assessment

June 2017

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249 Reads

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4 Citations

Lecture Notes in Computer Science

Breast cancer is the most prevalent cancer type in women, and while its survival rate is generally high the aesthetic outcome is an increasingly important factor when evaluating different treatment alternatives. 3D scanning and reconstruction techniques offer a flexible tool for building detailed and accurate 3D breast models that can be used both pre-operatively for surgical planning and post-operatively for aesthetic evaluation. This paper aims at comparing the accuracy of low-cost 3D scanning technologies with the significantly more expensive state-of-the-art 3D commercial scanners in the context of breast 3D reconstruction. We present results from 28 synthetic and clinical RGBD sequences, including 12 unique patients and an anthropomorphic phantom demonstrating the applicability of low-cost RGBD sensors to real clinical cases. Body deformation and homogeneous skin texture pose challenges to the studied reconstruction systems. Although these should be addressed appropriately if higher model quality is warranted, we observe that low-cost sensors are able to obtain valuable reconstructions comparable to the state-of-the-art within an error margin of 3 mm.


A comparative study of breast surface reconstruction for aesthetic outcome assessment

June 2017

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1 Read

Breast cancer is the most prevalent cancer type in women, and while its survival rate is generally high the aesthetic outcome is an increasingly important factor when evaluating different treatment alternatives. 3D scanning and reconstruction techniques offer a flexible tool for building detailed and accurate 3D breast models that can be used both pre-operatively for surgical planning and post-operatively for aesthetic evaluation. This paper aims at comparing the accuracy of low-cost 3D scanning technologies with the significantly more expensive state-of-the-art 3D commercial scanners in the context of breast 3D reconstruction. We present results from 28 synthetic and clinical RGBD sequences, including 12 unique patients and an anthropomorphic phantom demonstrating the applicability of low-cost RGBD sensors to real clinical cases. Body deformation and homogeneous skin texture pose challenges to the studied reconstruction systems. Although these should be addressed appropriately if higher model quality is warranted, we observe that low-cost sensors are able to obtain valuable reconstructions comparable to the state-of-the-art within an error margin of 3 mm.


Sentinel node detection in early breast cancer with intraoperative portable gamma camera: UK experience

April 2017

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50 Reads

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14 Citations

The Breast

Purpose: Access to nuclear medicine department for sentinel node imaging remains an issue in number of hospitals in the UK and many parts of the world. Sentinella(®) is a portable imaging camera used intra-operatively to produce real time visual localisation of sentinel lymph nodes. Methods: Sentinella(®) was tested in a controlled laboratory environment at our centre and we report our experience on the first use of this technology from UK. Moreover, preoperative scintigrams of the axilla were obtained in 144 patients undergoing sentinel node biopsy using conventional gamma camera. Sentinella(®) scans were done intra-operatively to correlate with the pre-operative scintigram and to determine presence of any residual hot node after the axilla was deemed to be clear based on the silence of the hand held gamma probe. Results: Sentinella(®) detected significantly more nodes compared with CGC (p < 0.0001). Sentinella(®) picked up extra nodes in 5/144 cases after the axilla was found silent using hand held gamma probe. In 2/144 cases, extra nodes detected by Sentinella(®) confirmed presence of tumour cells that led to a complete axillary clearance. Conclusions: Sentinella(®) is a reliable technique for intra-operative localisation of radioactive nodes. It provides increased nodal visualisation rates compared to static scintigram imaging and proves to be an important tool for harvesting all hot sentinel nodes. This portable gamma camera can definitely replace the use of conventional lymphoscintigrams saving time and money both for patients and the health system.


Abstract OT2-02-01: Photodynamic therapy for the treatment of primary breast cancer: Preliminary results of a phase I/IIa clinical trial

February 2017

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38 Reads

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9 Citations

Cancer Research

Background: Photodynamic therapy (PDT) has been used to treat skin metastases from breast cancer. We investigated the use of PDT for the treatment of primary breast cancer. Trial design: Phase I/IIA, open label, non-randomised, single site, light dose escalation trial in patients with primary breast cancer using verteporfin as the photosensitiser. Verteporfin 0.4mg/kg bodyweight is injected intravenously 60-90 minutes before laser activation through a thin optical fibre inserted percutaneously through a needle positioned under ultrasound guidance under local anaesthesia. The light dose is escalated from 20J to a maximum of 50J in intervals of 10J. Eligibility criteria: Patients aged 30 or over and have opted for mastectomy or wide local excision as primary treatment are included. The tumour should be uni-focal invasive ductal breast carcinoma, or discrete uni-focal site, within a multifocal invasive ductal carcinoma, in a single breast. Participants should not have confirmed distant metastases. The exclusion criteria include: patients who are not undergoing surgery as their primary treatment; patients undergoing surgery for DCIS without invasive breast cancer; lobular cancers and necrotic tumours; patients who have porphyria or are sensitive to verteporfin; patients who have severe cardiovascular disease or severe uncontrolled systemic disease (e.g. hepatic impairment); male breast cancer patients; pregnant or lactating patients; patients taking primary endocrine therapy or taking an experimental medicine as a part of a trial. Aims: We aim to establish the minimum light dose required to induce an area of necrosis with a diameter of at least 12mm perpendicular to the optical fibre; or to achieve a plateau with no increase in diameter of necrosis with increasing light dose. Secondary objectives are to examine the effect of Photodynamic Therapy on the abnormal breast tissue and study if necrosis extends to normal breast tissue. We will be assessing the role of MRI in predicting the response to treatment by measuring the diameter of tumour and the zone of necrosis before and after PDT and confirming it with histological findings. We will be monitoring the number of adverse events arising from the PDT. Statistical Methods: The sample size of the study is based on a standard 3+3 dose-escalation algorithm.Statistical analysis will be descriptive in nature with no formal statistical inference. Summary statistics and analysis will be provided for all patients who receive the study treatment, by dose level for each dosing regimen. Accrual Results: 11 patients have been enroled and completed the trial up to June 2016 with primary end point achieved and no adverse side- effects to treatment seen. Target Accrual: 21 patients. Acknowledgement: Royal Free Charity. Citation Format: Banerjee SM, Malhotra A, El-Sheikh S, Tsukagoshi D, Tran-Dang M-a, Mosse A, Parker S, Davidson TI, Williams NR, Bown S, Keshtgar MR. Photodynamic therapy for the treatment of primary breast cancer: Preliminary results of a phase I/IIa clinical trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT2-02-01.


Citations (50)


... 42 The majority of the studies report findings based on in vitro or animal studies, and evidence derived from the immune and inflammatory response of rats and rabbits differ from the normal human response. 23,63 Lastly, the Baker grading system used to classify the degree of CC is subjective in its nature and can potentiate the level of discrepancies in reporting and classifying the pathways observed. 64 ...

Reference:

Implant Texture and Capsular Contracture: A Review of Cellular and Molecular Pathways
Impact of post mastectomy radiotherapy on the silicone breast implant
  • Citing Article
  • December 2018

Materials Science and Engineering C

... (Colombo et al 2010, Park et al 2014, Kim et al 2015, Lee et al 2019, Yu et al 2023 Biomechanical testing provided the general range of effective elastic modulus for our lab-made miniature implants (171 ± 105 kPa). Published elastic moduli for commercial grade silicone implant shells alone range from 600 to 3000 kPa, and around 250 kPa for cohesive silicone gel infill; however, differences in implant size, outer shell to inner gel ratio, and material properties may contribute to variation between implants used herein and commercial models (Rynkevic et al 2013, Amoresano et al 2016, Magill et al 2019, Foroushani et al 2022. ...

Mechanical and Surface Chemical Analysis of Retrieved Breast Implants from a Single Centre
  • Citing Article
  • November 2018

Journal of the Mechanical Behavior of Biomedical Materials

... Adriamycin is an anthracycline antibiotic commonly used in the therapy of breast cancer, especially in patients with metastatic or recurrent tumors. 14,15 However, the emergence of resistance to adriamycin poses an enduring obstacle limiting the success of the treatment. Thus, there is an urgent need for strategies to successfully suppress tumor progression, drug resistance, and improve prognosis in breast cancer. ...

Aesthetic outcome after breast conserving surgery and either intraoperative radiotherapy or whole breast external beam radiotherapy for early breast cancer: Objective assessment of patients in a randomized controlled trial in Lublin, Poland
  • Citing Article
  • January 2017

European Journal of Gynaecological Oncology

... Further, the BCCT.core software has limitation with regard to the lack of 3-dimentional (3D) volume information 14 . ...

The value of 3D images in the aesthetic evaluation of breast cancer conservative treatment. Results from a prospective multicentric clinical trial

The Breast

... The TARGIT-A trial randomized 3451 patients to WBI (1730) or TARGIT-IORT (1721) to analyze toxicities and complications. Wound-related complications were similar between the two groups, but TARGIT-IORT had significantly fewer grade 3 or 4 toxicities and better cosmesis than WBI (63,64). TARGIT-IORT has also been shown to yield better breast-related quality of life and overall quality of life (65,66). ...

Cosmetic outcome as rated by patients, doctors, nurses and BCCT.core software assessed over 5 years in a subset of patients in the TARGIT-A Trial

Radiation Oncology

... Reversible electroporation has been used for breast cancer in several studies with promising results [10][11][12][13][14][15][16]. The electric voltage that is applied to the tumor lesion temporarily causes cell membrane poration and therefore increases drug uptake into the tumor cells multifold ( Figure 1A). ...

Electrochemotherapy for Breast Cancer – results from the INSPECT database
  • Citing Article
  • March 2018

Clinical Breast Cancer

... Software post-processing of 3D scans might take a long time, but still less than the time required for CT imaging (90 minutes) and MRI imaging (13-30 minutes). Moreover, two studies aimed to compare low-cost 3D systems to more expensive ones and concluded that they could be applied clinically 32,33 . It is important that the accuracy and reproducibility of measurements is maintained as there is a move towards smaller, lower-cost, and portable devices. ...

A Comparative Study of Breast Surface Reconstruction for Aesthetic Outcome Assessment

Lecture Notes in Computer Science

... Meanwhile, photodynamic therapy (PDT) plays an important role in the field of tumor treatment. 7,8 The photosensitizer in the new generation of photodynamic therapy (PDT) will transfer the energy to the surrounding oxygen and produce highly active singlet oxygen. Singlet oxygen can oxidize with nearby biological macromolecules to induce cytotoxicity and then kill tumor cells. ...

Abstract OT2-02-01: Photodynamic therapy for the treatment of primary breast cancer: Preliminary results of a phase I/IIa clinical trial
  • Citing Article
  • February 2017

Cancer Research

... The largest and most comprehensive study among those 26 selected is the pragmatic randomized con- trolled trial TARGIT-A [1,10]. Some further studies inclu- ded in the analysis were partial results from the individual centres involved in the TARGIT-A study [11][12][13][14][15][16][17][18]. From the point of view of the design and scope of the studies, TARGIT-A was the only reliable one. ...

Cosmetic outcome after intraoperative radiotherapy or external beam radiotherapy for early breast cancer: An objective assessment of patients from a randomized controlled trial.
  • Citing Article
  • September 2013

Journal of Clinical Oncology

... 21 CDS systems that could be classified as clinical pathways for care delivery processes were assessed in 6 of the 24 evaluated studies. [32][33][34][35][36][37] The primary outcome for each of these studies was the association of the clinical pathway CDS system with receipt of guideline-concordant or pathway-recommended care. In general, the outcomes associated with use of clinical pathway systems were compared with usual care; however, one study compared use of an electronic clinical pathway with a paper pathway. ...

Using computerized decision support to improve compliance of cancer multidisciplinary meetings with evidence-based guidance.
  • Citing Article
  • September 2012

Journal of Clinical Oncology