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Article ; Online: Neoadjuvant chemotherapy for locally advanced colonic cancer is not ready to be the standard of care.

Vimalachandran, Dale

2023 Volume 110, Issue 12, Page(s) 1677–1678

MeSH term(s)	Humans ; Neoadjuvant Therapy ; Standard of Care ; Disease-Free Survival ; Rectal Neoplasms/pathology ; Colonic Neoplasms/drug therapy ; Colonic Neoplasms/surgery ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Chemotherapy, Adjuvant ; Neoplasm Staging
Language	English
Publishing date	2023-09-23
Publishing country	England
Document type	Journal Article
ZDB-ID	2985-3
ISSN	1365-2168 ; 0263-1202 ; 0007-1323 ; 1355-7688
ISSN (online)	1365-2168
ISSN	0263-1202 ; 0007-1323 ; 1355-7688
DOI	10.1093/bjs/znad184
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Article ; Online: Individualized cancer vaccines versus surveillance after adjuvant chemotherapy for surgically resected high-risk stage 2 and stage 3 colorectal cancer: protocol for a randomized trial.

Jones, Robert P / Lee, Lennard Y W / Corrie, Pippa G / Danson, Sarah / Vimalachandran, Dale

The British journal of surgery

2023 Volume 110, Issue 12, Page(s) 1883–1884

MeSH term(s)	Humans ; Cancer Vaccines/therapeutic use ; Colonic Neoplasms/pathology ; Chemotherapy, Adjuvant/methods ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Neoplasm Staging ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/surgery ; Colorectal Neoplasms/pathology
Chemical Substances	Cancer Vaccines
Language	English
Publishing date	2023-10-19
Publishing country	England
Document type	Clinical Trial Protocol ; Journal Article
ZDB-ID	2985-3
ISSN	1365-2168 ; 0263-1202 ; 0007-1323 ; 1355-7688
ISSN (online)	1365-2168
ISSN	0263-1202 ; 0007-1323 ; 1355-7688
DOI	10.1093/bjs/znad332
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Article ; Online: Management of benign anastomotic strictures following rectal resection: a systematic review.

Clifford, Rachael Elizabeth / Fowler, Hayley / Manu, Nicola / Vimalachandran, Dale

Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland

2021 Volume 23, Issue 12, Page(s) 3090–3100

Abstract: Aim: Benign anastomotic strictures following colorectal surgical resection are a commonly under-reported complication in up to 30% of patients, with a significant impact upon quality of life. In this systematic review, we aim to assess the utility of ... ...

Abstract	Aim: Benign anastomotic strictures following colorectal surgical resection are a commonly under-reported complication in up to 30% of patients, with a significant impact upon quality of life. In this systematic review, we aim to assess the utility of endoscopic techniques in avoiding the need for surgical reintervention. Method: A literature search was performed for published full text articles using the PubMed, Cochrane and Scopus databases. Additional papers were found by scanning the references of relevant papers. Results: A total of 34 papers were included, focusing upon balloon dilatation, endoscopic stenting, electroincision, stapler stricturoplasty and cortiocosteroids alone and in combination, with success rates varying from 20% to 100%. The most challenging strictures were reported as those with a narrow lumen, frequently observed following neoadjuvant chemoradiotherapy or an anastomotic leak. Endoscopic balloon dilatation was the most commonly used first-line method; however, repeated dilatations were often required and this was associated with an increased risk of perforation. Although initial success rates for stents were good, patients often experienced stent migration and local symptoms. Only a small number of patients experienced endoscopic management failure and progressed to surgical intervention. Conclusion: Following identification of an anastomotic stricture and exclusion of underlying malignancy, endoscopic management is both safe and feasible as a first-line option, even if multiple treatment exposures or multimodal management is required. Surgical resection or a defunctioning stoma should be reserved for emergency or failed cases. Further research is required into multimodal and novel therapies to improve quality of life for these patients.
MeSH term(s)	Anastomosis, Surgical/adverse effects ; Anastomotic Leak/etiology ; Anastomotic Leak/surgery ; Constriction, Pathologic/etiology ; Constriction, Pathologic/surgery ; Dilatation ; Humans ; Quality of Life ; Retrospective Studies ; Stents ; Treatment Outcome
Language	English
Publishing date	2021-09-13
Publishing country	England
Document type	Journal Article ; Review ; Systematic Review
ZDB-ID	1440017-0
ISSN	1463-1318 ; 1462-8910
ISSN (online)	1463-1318
ISSN	1462-8910
DOI	10.1111/codi.15865
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Article ; Online: Proton beam therapy in rectal cancer: A systematic review and meta-analysis.

Fok, Matthew / Toh, Steven / Easow, Jeremy / Fowler, Hayley / Clifford, Rachael / Parsons, Jason / Vimalachandran, Dale

Surgical oncology

2021 Volume 38, Page(s) 101638

Abstract: Introduction: Locally advanced rectal cancer is often treated with neoadjuvant chemoradiotherapy and surgery. Radiotherapy carries significant risk of toxicity to organs at risk (OAR). Proton beam therapy (PBT) has demonstrated to be effective in other ... ...

Abstract	Introduction: Locally advanced rectal cancer is often treated with neoadjuvant chemoradiotherapy and surgery. Radiotherapy carries significant risk of toxicity to organs at risk (OAR). Proton beam therapy (PBT) has demonstrated to be effective in other cancers, delivering equivalent dosimetric radiation but with the benefit of improved sparing of OAR. This review compares dosimetric irradiation of OAR and oncological outcomes for PBT versus conventional photon-based radiotherapy in locally advanced rectal cancer. Methods: An electronic literature search was performed for studies with comparative cohorts receiving proton beam therapy and photon-based radiotherapy for rectal cancer. Results: Eight articles with a total of 127 patients met the inclusion criteria. There was significantly less irradiated small bowel with PBT compared to three-dimensional conformal radiation therapy (3DCRT) and intensity-modulated radiation therapy (IMRT) (MD -17.01, CI [-24.06, -9.96], p < 0.00001 and MD -6.96, CI [-12.99, -0.94], p = 0.02, respectively). Similar dosimetric results were observed for bladder and pelvic bone marrow. Three studies reported clinical and oncological results for PBT in recurrent rectal cancer with overall survival reported as 43 %, 68 % and 77.2 %, and one study in primary rectal cancer with 100 % disease free survival. Conclusion: PBT treatment plans revealed significantly less irradiation of OAR for rectal cancer compared to conventional photon-based radiotherapy. Trials for recurrent rectal cancer and PBT have shown promising results. There are currently no ongoing clinical trials for primary rectal cancer and PBT. More research is required to validate its potential role in dose escalation, higher complete response rate and organ preservation without increasing toxicity.
MeSH term(s)	Humans ; Proton Therapy ; Radiotherapy Dosage ; Radiotherapy, Intensity-Modulated ; Rectal Neoplasms/radiotherapy
Language	English
Publishing date	2021-07-27
Publishing country	Netherlands
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	1107810-8
ISSN	1879-3320 ; 0960-7404
ISSN (online)	1879-3320
ISSN	0960-7404
DOI	10.1016/j.suronc.2021.101638
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Zs.A 3409: Show issues

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Article ; Online: Sarcopenia estimation using psoas major enhances P-POSSUM mortality prediction in older patients undergoing emergency laparotomy: cross-sectional study.

Simpson, Gregory / Wilson, Jeremy / Vimalachandran, Dale / McNicol, Frances / Magee, Conor

European journal of trauma and emergency surgery : official publication of the European Trauma Society

2021 Volume 48, Issue 3, Page(s) 2003–2012

Abstract: Introduction: Emergency laparotomy is a considerable component of a colorectal surgeon's workload and conveys substantial morbidity and mortality, particularly in older patients. Frailty is associated with poorer surgical outcomes. Frailty and ... ...

Abstract	Introduction: Emergency laparotomy is a considerable component of a colorectal surgeon's workload and conveys substantial morbidity and mortality, particularly in older patients. Frailty is associated with poorer surgical outcomes. Frailty and sarcopenia assessment using Computed Tomography (CT) calculation of psoas major area predicts outcomes in elective and emergency surgery. Current risk predictors do not incorporate frailty metrics. We investigated whether sarcopenia measurement enhanced mortality prediction in over-65 s who underwent emergency laparotomy and emergency colorectal resection. Methods: An analysis of data collected prospectively during the National Emergency Laparotomy Audit (NELA) was conducted. Psoas major (PM) cross-sectional area was measured at the L3 level and a ratio of PM to L3 vertebral body area (PML3) was calculated. Outcome measures included inpatient, 30-day and 90-day mortality. Statistical analysis was conducted using Mann-Whitney, Chi-squared and receiver operating characteristics (ROC). Logistic regression was conducted using P-POSSUM variables with and without the addition of PML3. Results: Nine-hundred and forty-four over-65 s underwent emergency laparotomy from three United Kingdom hospitals were included. Median age was 76 years (IQR 70-82 years). Inpatient mortality was 21.9%, 30-day mortality was 16.3% and 90-day mortality was 20.7%. PML3 less than 0.39 for males and 0.31 for females indicated significantly worse outcomes (inpatient mortality 68% vs 5.6%, 30-day mortality 50.6% vs 4.0%,90-day mortality 64% vs 5.2%, p < 0.0001). PML3 was independently associated with mortality in multivariate analysis (p < 0.0001). Addition of PML3 to P-POSSUM variables improved area under the curve (AUC) on ROC analysis for inpatient mortality (P-POSSUM:0.78 vs P-POSSUM + PML3:0.917), 30-day mortality(P-POSSUM:0.802 vs P-POSSUM + PML3: 0.91) and 90-day mortality (P-POSSUM:0.79 vs P-POSSUM + PML3: 0.91). Conclusion: PML3 is an accurate predictor of mortality in over-65 s undergoing emergency laparotomy. Addition of PML3 to POSSUM appears to improve mortality risk prediction.
MeSH term(s)	Aged ; Colorectal Neoplasms/complications ; Cross-Sectional Studies ; Emergencies ; Female ; Frailty/complications ; Humans ; Laparotomy ; Male ; Retrospective Studies ; Risk Assessment ; Sarcopenia/diagnostic imaging
Language	English
Publishing date	2021-04-21
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2275480-5
ISSN	1863-9941 ; 1863-9933
ISSN (online)	1863-9941
ISSN	1863-9933
DOI	10.1007/s00068-021-01669-1
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Zs.A 1221: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Failure of nonoperative management in patients with acute diverticulitis complicated by abscess: a systematic review.

Fowler, Hayley / Gachabayov, Mahir / Vimalachandran, Dale / Clifford, Rachael / Orangio, Guy R / Bergamaschi, Roberto

International journal of colorectal disease

2021 Volume 36, Issue 7, Page(s) 1367–1383

Abstract: Background: The aim of this study was to assess failure rates following nonoperative management of acute diverticulitis complicated by abscess and trends thereof.: Method: Pubmed, MEDLINE, EMBASE, CINAHL, Cochrane Library, and Web of Science were ... ...

Abstract	Background: The aim of this study was to assess failure rates following nonoperative management of acute diverticulitis complicated by abscess and trends thereof. Method: Pubmed, MEDLINE, EMBASE, CINAHL, Cochrane Library, and Web of Science were systematically searched. Nonoperative management was defined as a combination of nil per os, IV fluids, IV antibiotics, CT scan-guided percutaneous drainage, and total parenteral nutrition. The primary endpoint was failure of nonoperative management defined as persistent or worsening abscess and/or sepsis, development of new complications, such as peritonitis, ileus, or colocutaneous fistula, and urgent surgery within 30-90 days of index admission. Data were stratified by three arbitrary time intervals: 1986-2000, 2000-2010, and after 2010. The primary outcome was calculated for those groups and compared. Results: Thirty-eight of forty-four eligible studies published between 1986 and 2019 were included in the quantitative synthesis of data (n = 2598). The pooled rate of failed nonoperative management was 16.4% (12.6%, 20.2%) at 90 days. In studies published in 2000-2010 (n = 405), the pooled failure rate was 18.6% (10.5%, 26.7%). After 2000 (n = 2140), the pooled failure rate was 15.3% (10.7%, 20%). The difference was not statistically significant (p = 0.725). After controlling for heterogeneity in the definition of failure of nonoperative management, subgroup analysis yielded the pooled rate of failure of 21.8% (16.1%, 27.4%). Conclusion: This meta-analysis found that failure rates following nonoperative management of acute diverticulitis complicated by abscess did not significantly decrease over the past three decades. The general quality of published data and the level and certainty of evidence produced were low.
MeSH term(s)	Abscess/therapy ; Diverticulitis ; Diverticulitis, Colonic ; Drainage ; Humans ; Peritonitis
Language	English
Publishing date	2021-03-07
Publishing country	Germany
Document type	Journal Article ; Meta-Analysis ; Review ; Systematic Review
ZDB-ID	84975-3
ISSN	1432-1262 ; 0179-1958
ISSN (online)	1432-1262
ISSN	0179-1958
DOI	10.1007/s00384-021-03899-6
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Article ; Online: Impact on blood loss and transfusion rates following administration of tranexamic acid in major oncological abdominal and pelvic surgery: A systematic review and meta-analysis.

Fowler, Hayley / Law, Jennifer / Tham, Su Ming / Gunaravi, Sisyena A / Houghton, Neil / Clifford, Rachael E / Fok, Matthew / Barker, Jonathan A / Vimalachandran, Dale

Journal of surgical oncology

2022 Volume 126, Issue 3, Page(s) 609–621

Abstract: Background and objectives: Major bleeding and receiving blood products in cancer surgery are associated with increased postoperative complications and worse outcomes. Tranexamic acid (TXA) reduces blood loss and improves outcomes in various surgical ... ...

Abstract	Background and objectives: Major bleeding and receiving blood products in cancer surgery are associated with increased postoperative complications and worse outcomes. Tranexamic acid (TXA) reduces blood loss and improves outcomes in various surgical specialities. We performed a systematic review and meta-analysis to investigate TXA use on blood loss in elective abdominal and pelvic cancer surgery. Methods: A literature search was performed for studies comparing intravenous TXA versus placebo/no TXA in patients undergoing major elective abdominal or pelvic cancer surgery. Results: Twelve articles met the inclusion criteria, consisting of 723 patients who received TXA and 659 controls. Patients receiving TXA were less likely to receive a red blood cell (RBC) transfusion (p < 0.001, OR 0.4 95% CI [0.25, 0.63]) and experienced less blood loss (p < 0.001, MD -197.8 ml, 95% CI [-275.69, -119.84]). The TXA group experienced a smaller reduction in haemoglobin (p = 0.001, MD -0.45 mmol/L, 95% CI [-0.73, -0.18]). There was no difference in venous thromboembolism (VTE) rates (p = 0.95, OR 0.98, 95% CI [0.46, 2.08]). Conclusions: TXA use reduced blood loss and RBC transfusion requirements perioperatively, with no significant increased risk of VTE. However, further studies are required to assess its benefit for cancer surgery in some sub-specialities.
MeSH term(s)	Antifibrinolytic Agents ; Blood Loss, Surgical/prevention & control ; Humans ; Pelvic Neoplasms/surgery ; Tranexamic Acid ; Venous Thromboembolism
Chemical Substances	Antifibrinolytic Agents ; Tranexamic Acid (6T84R30KC1)
Language	English
Publishing date	2022-04-26
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	82063-5
ISSN	1096-9098 ; 0022-4790
ISSN (online)	1096-9098
ISSN	0022-4790
DOI	10.1002/jso.26900
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Zs.A 706: Show issues

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Article ; Online: Measuring sarcopenia on pre-operative CT in older adults undergoing emergency laparotomy: a comparison of three different calculations.

Simpson, Gregory / Manu, Nichola / Magee, Conor / Wilson, Jeremy / Moug, Susan / Vimalachandran, Dale

International journal of colorectal disease

2020 Volume 35, Issue 6, Page(s) 1095–1102

Abstract: Introduction: Sarcopenia is associated with outcomes in older-adults undergoing emergency surgery. Psoas major measurement is a surrogate marker of sarcopenia with multiple calculations existing normalising to body size and no consensus as to which is ... ...

Abstract	Introduction: Sarcopenia is associated with outcomes in older-adults undergoing emergency surgery. Psoas major measurement is a surrogate marker of sarcopenia with multiple calculations existing normalising to body size and no consensus as to which is optimal. We compared three different psoas-major calculations to predict outcomes in older adults undergoing emergency laparotomy. Methods: Consecutive over 65s were identified from the National Emergency Laparotomy Audit(NELA) database at a single centre between 2014 and 2018. Psoas major was measured at the L3 level and normalised to height (psoas muscle index, PMI), L3 vertebral body (psoas muscle:L3 ratio, PML3) or body surface area (psoas:body surface area, PBSA) and each correlated to outcomes. Outcome measures included inpatient, 30-day and 90-day mortality. A comparison of the three calculations was performed using the Mann-Whitney U, chi-squared, receiver operating characteristic curves (ROC) and binary logistic regression. Results: Two hundred and sixty-four older adults underwent emergency laparotomy (median age, 75 years ((IQR, 70-81 years), 50% female)). Inpatient mortality was 19.6%, 30-day mortality was 15.1% and 90-day mortality was 18.5%. A total of 31.1% of males and 30% of females were sarcopenic (30.6% overall). A multivariate analysis confirmed each method of psoas major calculation (p < 0.0001) to be associated with mortality, as was ASA-grade (p < 0.0001). Area under the curve (AUC) was greatest for PML3 in predicting mortality (inpatient: PML3, 0.76; PMI, 0.71; PBSA, 0.70; 30-day: PML3, 0.74; PMI, 0.68; PBSA, 0.68; and 90-day: PML3, 0.78; PMI, 0.71; PBSA, 0.70). ASA-grade, P-POSSUM and PML3 were independently associated with mortality on multivariate analysis. ROC analysis of predictions from logistic regression models demonstrated PML3 to be more closely aligned to mortality than ASA or P-POSSUM (inpatient: AUC:PML3, 0.807; ASA, 0.783; P-POSSUM, 0.762; 30-day:AUC: PML3, 0.799; ASA, 0.784; P-POSSUM, 0.787; and 90-day: AUC:PML3, 0.805; ASA, 0.781; P-POSSUM, 0.756). Conclusions: Sarcopenia was present in 30.6% of older adults undergoing emergency surgery and is associated with a significantly increased mortality. PML3 is superior to PMI or PBSA and should be considered the method of calculation of choice. Additionally, PML3 compares favourably to ASA and P-POSSUM.
MeSH term(s)	Aged ; Aged, 80 and over ; Area Under Curve ; Body Height ; Body Surface Area ; Emergencies ; Female ; Health Status Indicators ; Hospital Mortality ; Humans ; Intestinal Diseases/complications ; Intestinal Diseases/surgery ; Kaplan-Meier Estimate ; Lumbar Vertebrae/diagnostic imaging ; Male ; Organ Size ; Preoperative Period ; Psoas Muscles/diagnostic imaging ; Psoas Muscles/pathology ; ROC Curve ; Retrospective Studies ; Risk Assessment/methods ; Sarcopenia/complications ; Sarcopenia/diagnostic imaging ; Sarcopenia/mortality ; Sarcopenia/pathology ; Tomography, X-Ray Computed ; United Kingdom/epidemiology
Language	English
Publishing date	2020-03-25
Publishing country	Germany
Document type	Comparative Study ; Journal Article
ZDB-ID	84975-3
ISSN	1432-1262 ; 0179-1958
ISSN (online)	1432-1262
ISSN	0179-1958
DOI	10.1007/s00384-020-03570-6
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Article ; Online: Intra-operative assessment of left-sided colorectal anastomotic integrity: a systematic review of available techniques.

Clifford, Rachael E / Fowler, Hayley / Manu, Nicola / Sutton, Paul / Vimalachandran, Dale

Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland

2020 Volume 23, Issue 3, Page(s) 582–591

Abstract: Aim: Anastomotic leak (AL) after colorectal resection is associated with increased rates of morbidity and mortality: potential permanent stoma formation, increased local recurrence, reduced cancer-related survival, poor functional outcomes and ... ...

Abstract	Aim: Anastomotic leak (AL) after colorectal resection is associated with increased rates of morbidity and mortality: potential permanent stoma formation, increased local recurrence, reduced cancer-related survival, poor functional outcomes and associated quality of life. Techniques to reduce leak rates are therefore highly sought. Method: A literature search was performed for published full text articles using PubMed, Cochrane and Scopus databases with a focus on colorectal surgery 1990-2020. Additional papers were detected by scanning references of relevant papers. Results: A total of 53 papers were included after a thorough literature search. Techniques assessed included leak tests, endoscopy, perfusion assessment and fluorescence studies. Air-leak testing remains the most commonly used method across Europe, due to ease of reproducibility and low cost. There is no evidence that this reduces the leak rate; however, identification of a leak intra-operatively provides the opportunity for either suture reinforcement or formal takedown with or without re-do of the anastomosis and consideration of diversion. Suture repair alone of a positive air-leak test is associated with an increased AL rate. The use of fluorescence studies to guide the site of anastomosis has demonstrated reduced leak rates in distal anastomoses, is safe, feasible and has a promising future. Conclusion: Although over reliance on any assessment tool should be avoided, intra-operative techniques with the aim of reducing AL rates are increasingly being employed. Standardization of these methods is imperative for routine use. However, in the interim it is recommended that all anastomoses should be assessed intra-operatively for mechanical failure, particularly distal anastomoses.
MeSH term(s)	Anastomosis, Surgical/adverse effects ; Anastomotic Leak/etiology ; Anastomotic Leak/prevention & control ; Colorectal Neoplasms/surgery ; Humans ; Quality of Life ; Reproducibility of Results
Language	English
Publishing date	2020-10-25
Publishing country	England
Document type	Journal Article ; Review ; Systematic Review
ZDB-ID	1440017-0
ISSN	1463-1318 ; 1462-8910
ISSN (online)	1463-1318
ISSN	1462-8910
DOI	10.1111/codi.15380
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Zs.A 5799: Show issues

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Article ; Online: Enhancing radiotherapy outcomes in rectal cancer: A systematic review of targeting hypoxia-induced radioresistance.

Fok, Matthew / Hill, Rhianna / Fowler, Hayley / Clifford, Rachael / Kler, Aaron / Uzzi-Daniel, Jayanma / Rocha, Sonia / Grundy, Gabrielle / Parsons, Jason / Vimalachandran, Dale

Clinical and translational radiation oncology

2023 Volume 44, Page(s) 100695

Abstract: Introduction: Neoadjuvant radiotherapy is successfully used in rectal cancer to improve overall survival. However, treatment response is both unpredictable and variable. There is strong evidence to show that the phenomenon of tumour hypoxia is ... ...

Abstract	Introduction: Neoadjuvant radiotherapy is successfully used in rectal cancer to improve overall survival. However, treatment response is both unpredictable and variable. There is strong evidence to show that the phenomenon of tumour hypoxia is associated with radioresistance, however the mechanism(s) behind this are poorly understood. Consequently, there have only been a small number of studies evaluating methods targeting hypoxia-induced radioresistance. The purpose of this systematic review is to evaluate the potential effectiveness of targeting hypoxia-induced radioresistance in rectal cancer and provide recommendations for future research in this area. Methods: A comprehensive literature search was performed following the PRISMA guidelines. This study was registered on the Prospero database (CRD42023441983). Results: Eight articles met the inclusion criteria. All studies identified were Discussion: The importance of investigating hypoxia-induced radioresistance in rectal cancer is crucial. However, to date, only a small number of preclinical studies exist evaluating this phenomenon. This systematic review highlights the importance of further research to fully understand the mechanism behind this radioresistance. There are promising targets identified in this systematic review however, substantially more pre-clinical and clinical research as a priority for future research is needed.
Language	English
Publishing date	2023-10-28
Publishing country	Ireland
Document type	Journal Article
ISSN	2405-6308
ISSN (online)	2405-6308
DOI	10.1016/j.ctro.2023.100695
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