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Article ; Online: Concepts and prospects of minimally invasive colorectal cancer surgery.

Merchant, J / McArthur, D / Ferguson, H / Ramcharan, S

2021 Volume 76, Issue 12, Page(s) 889–895

Abstract: It is important that clinical radiologists understand and appreciate the minimally invasive surgery (MIS) options available to surgeons. Operative technologies are constantly evolving, and accurate, informed interpretation of clinical imaging is ... ...

Abstract	It is important that clinical radiologists understand and appreciate the minimally invasive surgery (MIS) options available to surgeons. Operative technologies are constantly evolving, and accurate, informed interpretation of clinical imaging is essential for optimum surgical management. Concurrent advancements in both MIS and radiological staging have certainly improved treatment decisions and outcomes. This article outlines the history, current concepts, evolving techniques, and future prospects of MIS as it pertains to colorectal cancer surgery.
MeSH term(s)	Colorectal Neoplasms/diagnostic imaging ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/surgery ; Humans ; Minimally Invasive Surgical Procedures ; Robotic Surgical Procedures
Language	English
Publishing date	2021-10-13
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	391227-9
ISSN	1365-229X ; 0009-9260
ISSN (online)	1365-229X
ISSN	0009-9260
DOI	10.1016/j.crad.2021.09.013
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Article: Targeting mTOR and Survivin Concurrently Potentiates Radiation Therapy in Renal Cell Carcinoma by Suppressing DNA Damage Repair and Amplifying Mitotic Catastrophe.

Rachamala, Hari K / Madamsetty, Vijay S / Angom, Ramcharan S / Nakka, Naga M / Kumar Dutta, Shamit / Wang, Enfeng / Mukhopadhyay, Debabrata / Pal, Krishnendu

Research square

2023

Abstract: Background: Renal cell carcinoma (RCC) was historically considered to be less responsive to radiation therapy (RT) compared to other cancer indications. However, advancements in precision high-dose radiation delivery through single-fraction and multi- ... ...

Abstract	Background: Renal cell carcinoma (RCC) was historically considered to be less responsive to radiation therapy (RT) compared to other cancer indications. However, advancements in precision high-dose radiation delivery through single-fraction and multi-fraction stereotactic ablative radiotherapy (SABR) have led to better outcomes and reduced treatment-related toxicities, sparking renewed interest in using RT to treat RCC. Moreover, numerous studies have revealed that certain therapeutic agents including chemotherapies can increase the sensitivity of tumors to RT, leading to a growing interest in combining these treatments. Here, we developed a rational combination of two radiosensitizers in a tumor-targeted liposomal formulation for augmenting RT in RCC. The objective of this study is to assess the efficacy of a tumor-targeted liposomal formulation combining the mTOR inhibitor everolimus (E) with the survivin inhibitor YM155 (Y) in enhancing the sensitivity of RCC tumors to radiation. Experimental design: We slightly modified our previously published tumor-targeted liposomal formulation to develop a rational combination of E and Y in a single liposomal formulation (EY-L) and assessed its efficacy in RCC cell lines in vitro and in RCC tumors in vivo. We further investigated how well EY-L sensitizes RCC cell lines and tumors toward radiation and explored the underlying mechanism of radiosensitization. Results: EY-L outperformed the corresponding single drug-loaded formulations E-L and Y-L in terms of containing primary tumor growth and improving survival in an immunocompetent syngeneic mouse model of RCC. EY-L also exhibited significantly higher sensitization of RCC cells towards radiation in vitro than E-L and Y-L. Additionally, EY-L sensitized RCC tumors towards radiation therapy in xenograft and murine RCC models. EY-L mediated induction of mitotic catastrophe via downregulation of multiple cell cycle checkpoints and DNA damage repair pathways could be responsible for the augmentation of radiation therapy. Conclusion: Taken together, our study demonstrated the efficacy of a strategic combination therapy in sensitizing RCC to radiation therapy via inhibition of DNA damage repair and a substantial increase in mitotic catastrophe. This combination therapy may find its use in the augmentation of radiation therapy during the treatment of RCC patients.
Language	English
Publishing date	2023-12-23
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3770403/v1
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Article ; Online: The benefits of index telephone consultations in patients referred on the two-week wait colorectal cancer pathway.

Wanigasooriya, K / Sarma, D R / Woods, P / O'Connor, P / Matthews, A / Aslam, M I / Dando, C / Ferguson, H / Francombe, J / Lal, N / Murphy, P D / Papettas, T / Ramcharan, S / Busby, K

Annals of the Royal College of Surgeons of England

2022 Volume 105, Issue 4, Page(s) 314–322

Abstract: Introduction: The coronavirus disease 2019 (COVID-19) pandemic led to hospitals in the UK substituting face-to-face (FtF) clinics with virtual clinic (VC) appointments. We evaluated the use of virtual two-week wait (2-ww) lower gastrointestinal (LGI) ... ...

Abstract	Introduction: The coronavirus disease 2019 (COVID-19) pandemic led to hospitals in the UK substituting face-to-face (FtF) clinics with virtual clinic (VC) appointments. We evaluated the use of virtual two-week wait (2-ww) lower gastrointestinal (LGI) clinic appointments, conducted using telephone calls at a district general hospital in England. Methods: Patients undergoing index outpatient 2-ww LGI clinic assessment between 1 June 2019 and 31 October 2019 (FtF group) and 1 June 2020 and 31 October 2020 (VC group) were identified. Relevant data were obtained using electronic patient records. Compliance with national cancer waiting time targets was assessed. Environmental and financial impact analyses were performed. Results: In total, 1,531 patients were analysed (median age=70, male=852, 55.6%). Of these, 757 (49.4%) were assessed virtually via telephone; the remainder were seen FtF ( Conclusion: Virtual 2-ww LGI clinics were effective, safe and were associated with tangible environmental and financial benefits.
MeSH term(s)	Humans ; Male ; Aged ; Referral and Consultation ; COVID-19/epidemiology ; Telephone ; Appointments and Schedules ; Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/therapy
Language	English
Publishing date	2022-04-29
Publishing country	England
Document type	Journal Article
ZDB-ID	80044-2
ISSN	1478-7083 ; 0035-8843
ISSN (online)	1478-7083
ISSN	0035-8843
DOI	10.1308/rcsann.2021.0364
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Article: Oral contraceptive estrogen content and adverse effects.

Russell, M / Ramcharan, S

Canadian family physician Medecin de famille canadien

2010 Volume 33, Page(s) 445–460

Abstract: The 1985 Health and Welfare Canada Report on Oral Contraceptives recommended oral contraceptives (OCs) containing 30-35 mcg of estrogen rather than 50 mcg as the preferred dosage for contraception. Many family physicians may regard these guidelines as ... ...

Abstract	The 1985 Health and Welfare Canada Report on Oral Contraceptives recommended oral contraceptives (OCs) containing 30-35 mcg of estrogen rather than 50 mcg as the preferred dosage for contraception. Many family physicians may regard these guidelines as mandatory when prescribing OCs, because of a presumption that pills of 50-mcg estrogen content carry a higher risk of disease. In this article, the epidemiologic evidence pertaining to a dose-response relationship between the estrogen dose of oral contraceptives and disease is critically reviewed. The review indicates that there is no incontrovertible evidence to support such a relationship. Implications of the recommendations in the Report for physicians and patients are discussed.
Language	English
Publishing date	2010-12-16
Publishing country	Canada
Document type	Journal Article
ZDB-ID	603565-6
ISSN	0008-350X
ISSN	0008-350X
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Article ; Online: Is it time for one-step nucleic acid amplification (OSNA) in colorectal cancer? A systematic review and meta-analysis.

Wild, J B / Iqbal, N / Francombe, J / Papettas, T / Sanders, D S / Ramcharan, S

Techniques in coloproctology

2017 Volume 21, Issue 9, Page(s) 693–699

Abstract: Background: Lymph node metastasis (LNM) is prognostic in colorectal cancer (CRC). However, evaluation by routine haematoxylin and eosin histology (HE) limits nodal examination and is subjective. Missed LNMs from tissue allocation bias (TAB) might under- ... ...

Abstract	Background: Lymph node metastasis (LNM) is prognostic in colorectal cancer (CRC). However, evaluation by routine haematoxylin and eosin histology (HE) limits nodal examination and is subjective. Missed LNMs from tissue allocation bias (TAB) might under-stage disease, leading to under-treatment. One-step nucleic acid amplification (OSNA) for CK19 messenger ribonucleic acid (mRNA), a marker of LNM, analyses the whole node. The aim of the present systematic review and meta-analysis was to assess recent studies on OSNA versus HE and its implications for CRC staging and treatment. Methods: Databases including OVID, Medline and Google Scholar were searched for OSNA, LNM and CRC. Study results were pooled using a random-effects model. Summary receiver operator curves (SROC) assessed OSNA's performance in detecting LNM when compared to routine HE histology. Results: Five case-control studies analysing 4080 nodes from 622 patients were included. The summary estimates of pooled results for OSNA were sensitivity 0.90 [95% confidence interval (CI) 0.86-0.93], specificity 0.94 (95% CI 0.93-0.95) and diagnostic odds ratio 179.5 (CI 58.35-552.2, p < 0.0001). The SROC curve indicated a maximum joint sensitivity and specificity of 0.88 and area under the curve of 0.94, p < 0.0001. On average, 5.4% HE-negative nodes were upstaged by OSNA. Conclusions: OSNA is as good as routine HE. It may avoid TAB and offer a more objective and standardised assay of LNM. However, for upstaging, its usefulness as an adjunct to HE or superiority to HE requires further assessment of the benefits, if any, of adjuvant therapy in patients upstaged by OSNA.
Language	English
Publishing date	2017-09
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2083309-X
ISSN	1128-045X ; 1123-6337
ISSN (online)	1128-045X
ISSN	1123-6337
DOI	10.1007/s10151-017-1690-0
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Article: Colonoscopy without sedation: Patient factors alone are less likely to influence its uptake.

Iqbal, Nusrat / Ramcharan, Sean / Doughan, Samer / Shaikh, Irshad

Endoscopy international open

2016 Volume 4, Issue 5, Page(s) E534–7

Abstract: Background and study aims: Conscious sedation during colonoscopy minimizes discomfort, improves polyp detection rates, and reduces technical failure, but carries medication-related risks and requires dedicated and costly recovery services. Sedation-free ...

Abstract	Background and study aims: Conscious sedation during colonoscopy minimizes discomfort, improves polyp detection rates, and reduces technical failure, but carries medication-related risks and requires dedicated and costly recovery services. Sedation-free procedures may offer a safer alternative. We aimed to compare this group with those receiving sedation to determine differences in patient characteristics, cecal intubation rates, polyp detection rates, discomfort levels and safety in patients for whom anesthesia is high risk. Patients and methods: Prospectively collected data from all colonoscopies performed over a 1-year period at three district general hospitals were analyzed. Conscious sedation was offered to all patients and outcomes in those who refused were compared with outcomes in those who received sedation. Results: One hundred ninety-four of 1694 (11 %) colonoscopies were performed without sedation (61 % male, P < 0.001) but rates varied between hospitals. Of these, 55 % were American Society of Anesthesiologists (ASA) grade 3 or more and 5 % experienced moderate discomfort, compared to 40 % (P < 0.0001) and 10 % (P = 0.023) respectively of those receiving sedation. They were more likely to have indications of rectal bleeding or frequency of stool and less likely to have anaemia or macroscopic inflammation at colonoscopy. Complications, completion. and polyp detection rates were similar in both groups. Conclusions: Colonoscopy without sedation can be completed successfully in select patients without compromising comfort or polyp detection rates and is safe in those for whom anesthesia is high risk. It is therefore a safe alternative for clinicians concerned about sedation, but the findings suggest that hospital, rather than patient factors, may prevent its uptake.
Language	English
Publishing date	2016-05-03
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2761052-4
ISSN	2196-9736 ; 2364-3722
ISSN (online)	2196-9736
ISSN	2364-3722
DOI	10.1055/s-0042-102877
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Article ; Online: Needleless Electrohydrodynamic Cojetting of Bicompartmental Particles and Fibers from an Extended Fluid Interface.

Jordahl, Jacob H / Ramcharan, Stacy / Gregory, Jason V / Lahann, Joerg

Macromolecular rapid communications

2017 Volume 38, Issue 1

Abstract: Electrohydrodynamic cojetting can result in fibers (electrospinning) and particles (electrospraying) with complex, bicompartmental architectures. An important consideration for application of bicompartmental particles and fibers is the limited throughput ...

Abstract	Electrohydrodynamic cojetting can result in fibers (electrospinning) and particles (electrospraying) with complex, bicompartmental architectures. An important consideration for application of bicompartmental particles and fibers is the limited throughput derived from the use of parallel capillaries, which require laminar flow to form a multifluidic interface. Here, a novel synthesis approach that takes advantage of an extended bicompartmental fluid interface formed at the sharp edge of a 2D plate is reported. Upon application of an electrical potential to the plate, several electrified fluid jets form spontaneously. Depending on the processing conditions, either bicompartmental particles or fibers with well-defined architectures are prepared. Importantly, this needleless process yields production rates that are more than 30 times higher than those of conventional needle-based techniques. Fiber properties, such as morphology or size, are independent of the flow rate, indicating that this process is physically self-regulating by adjusting the number of jets ejecting from the extended fluid interface. The needleless preparation of bicompartmental particles and fibers is an important technological breakthrough that can enable further advances ranging from drug delivery and tissue engineering to industrial applications.
MeSH term(s)	Biocompatible Materials/chemistry ; Electric Conductivity ; Electrochemical Techniques/instrumentation ; Hydrodynamics ; Particle Size ; Surface Properties
Chemical Substances	Biocompatible Materials
Language	English
Publishing date	2017-01
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1475027-2
ISSN	1521-3927 ; 1022-1336
ISSN (online)	1521-3927
ISSN	1022-1336
DOI	10.1002/marc.201600437
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Article: Surgery for gallstone disease during pregnancy does not increase fetal or maternal mortality: a meta-analysis.

Athwal, Ruvinder / Bhogal, Ricky Harminder / Hodson, James / Ramcharan, Sean

Hepatobiliary surgery and nutrition

2016 Volume 5, Issue 1, Page(s) 53–57

Abstract: Background: Pregnancy was traditionally considered a contraindication to cholecystectomy but is now becoming the favoured option for gallstone-related disease (GRD) during pregnancy.: Methods: To assess if cholecystectomy during pregnancy increases ... ...

Abstract	Background: Pregnancy was traditionally considered a contraindication to cholecystectomy but is now becoming the favoured option for gallstone-related disease (GRD) during pregnancy. Methods: To assess if cholecystectomy during pregnancy increases the risk of preterm labour, fetal mortality and maternal mortality. PubMed and MEDLINE databases for the period from January 1966 through December 2013. Studies were both conservative and surgical intervention was utilised in the management of GRD were included. The results of the included studies were pooled using meta-analysis techniques. Results: Surgical intervention for GRD in pregnancy does not increase the risk of preterm labour, fetal mortality or maternal mortality. Conclusions: Cholecystectomy during pregnancy for GRD is associated with low complications for the fetus and mother and should be considered in all suitable patients.
Language	English
Publishing date	2016-02-08
Publishing country	China (Republic : 1949- )
Document type	Journal Article
ZDB-ID	2812398-0
ISSN	2304-389X ; 2304-3881
ISSN (online)	2304-389X
ISSN	2304-3881
DOI	10.3978/j.issn.2304-3881.2015.11.02
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Article ; Online: Nontraumatic Emergency Laparotomy: Surgical Principles Similar to Trauma Need to Be Adopted?

Singh-Ranger, Deepak / Leung, Edmund / Lau-Robinson, Mei-Ling / Ramcharan, Sean / Francombe, James

Southern medical journal

2017 Volume 110, Issue 11, Page(s) 688–693

Abstract: Objectives: In 2011, the Royal College of Surgeons published : Methods: All patients who underwent emergency laparotomy between April 2011 and December 2012 at Warwick Hospital (Warwick, UK) were included retrospectively. Information relating to ... ...

Abstract	Objectives: In 2011, the Royal College of Surgeons published Methods: All patients who underwent emergency laparotomy between April 2011 and December 2012 at Warwick Hospital (Warwick, UK) were included retrospectively. Information relating to their demographics; preoperative score; primary pathology; timing of surgery; intraoperative details; and postoperative outcome, including 30-day mortality, were collated for statistical analysis. Results: In total, 91 patients underwent 97 operations. The median age was 64 years (range 50-90, male:female 1:2). Sixty-five percent of cases were obstruction and perforation, and 66% of all operations were performed during office hours. The unadjusted 30-day mortality was 15.4%. Compared with nonsurvivors, survivors had a significantly higher Portsmouth-Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity score ( Conclusions: The 30-day mortality rate is comparable to the national standard. Further studies are warranted to determine whether trauma management modalities may be adopted to target high-risk patients who exhibit the lethal triad of hypotension, coagulopathy, and hypothermia.
Language	English
Publishing date	2017-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	185329-6
ISSN	1541-8243 ; 0038-4348
ISSN (online)	1541-8243
ISSN	0038-4348
DOI	10.14423/SMJ.0000000000000721
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Article ; Online: Convergence of coronary artery disease genes onto endothelial cell programs.

Schnitzler, Gavin R / Kang, Helen / Fang, Shi / Angom, Ramcharan S / Lee-Kim, Vivian S / Ma, X Rosa / Zhou, Ronghao / Zeng, Tony / Guo, Katherine / Taylor, Martin S / Vellarikkal, Shamsudheen K / Barry, Aurelie E / Sias-Garcia, Oscar / Bloemendal, Alex / Munson, Glen / Guckelberger, Philine / Nguyen, Tung H / Bergman, Drew T / Hinshaw, Stephen /

Cheng, Nathan / Cleary, Brian / Aragam, Krishna / Lander, Eric S / Finucane, Hilary K / Mukhopadhyay, Debabrata / Gupta, Rajat M / Engreitz, Jesse M

Nature

2024 Volume 626, Issue 8000, Page(s) 799–807

Abstract: Linking variants from genome-wide association studies (GWAS) to underlying mechanisms of disease remains a ... ...

Abstract	Linking variants from genome-wide association studies (GWAS) to underlying mechanisms of disease remains a challenge
MeSH term(s)	Humans ; Coronary Artery Disease/genetics ; Coronary Artery Disease/pathology ; Endothelial Cells/metabolism ; Endothelial Cells/pathology ; Genetic Predisposition to Disease/genetics ; Genome-Wide Association Study ; Hemangioma, Cavernous, Central Nervous System/genetics ; Hemangioma, Cavernous, Central Nervous System/pathology ; Polymorphism, Single Nucleotide ; Epigenomics ; Signal Transduction/genetics ; Multifactorial Inheritance
Chemical Substances	CCM2 protein, human ; TLNRD1 protein, human
Language	English
Publishing date	2024-02-07
Publishing country	England
Document type	Journal Article
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-024-07022-x
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