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1.
Int J Mol Sci ; 25(7)2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38612815

ABSTRACT

This systematic review investigates the potential of circulating tumour DNA (ctDNA) as a predictive biomarker in the management and prognosis of squamous cell carcinoma of the anal canal (SCCA). PubMed, EMBASE, and Cochrane Central Registry of Controlled Trials were searched until 7 January 2024. Selection criteria included research articles exploring ctDNA in the context of anal cancer treatment response, recurrence risk assessment, and consideration of salvage surgery. A total of eight studies were therefore included in the final review, examining a total of 628 patients. These studies focused on three main themes: SCCA diagnosis and staging, treatment response, and patient outcomes. Significant heterogeneity was observed in terms of patient cohort, study methodology, and ctDNA biomarkers. Four studies provided information on the sensitivity of ctDNA biomarkers in SCCA, with a range of 82-100%. Seven studies noted a correlation between pre-treatment ctDNA levels and SCCA disease burden, suggesting that ctDNA could play a role as a biomarker for the staging of SCCA. Across all seven studies with paired pre- and post-treatment ctDNA samples, a trend was seen towards decreasing ctDNA levels post-treatment, with specific identification of a 'fast elimination' group who achieve undetectable ctDNA levels prior to the end of treatment and may be less likely to experience treatment failure. Residual ctDNA detection post-treatment was associated with poorer patient prognosis. This systematic review identifies the broad potential of ctDNA as a useful and decisive tool in the management of SCCA. Further analysis of ctDNA biomarkers that include larger patient cohorts is required in order to clearly evaluate their potential role in clinical decision-making processes.


Subject(s)
Anus Neoplasms , Biomarkers, Tumor , Circulating Tumor DNA , Humans , Circulating Tumor DNA/blood , Circulating Tumor DNA/genetics , Anus Neoplasms/blood , Anus Neoplasms/therapy , Anus Neoplasms/genetics , Anus Neoplasms/diagnosis , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Prognosis , Carcinoma, Squamous Cell/blood , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/diagnosis
2.
J Surg Oncol ; 127(4): 645-656, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36350234

ABSTRACT

BACKGROUND: Synchronous para-aortic lymph node metastasis (PALNM) in colorectal cancer (CRC) is a relatively rare clinical entity. There is a lack of consensus on management of these patients, and the role of para-aortic lymph node dissection (PALND) remains controversial. This systematic review aims to describe the survival outcomes in colorectal cancer with synchronous PALNM when lymph node dissection is performed. METHODS: A systematic review of Pubmed, Embase and Web of Science databases for PALND in CRC was performed. Studies including patients with synchronous PALNM undergoing resection with curative intent, published from the year 2000 onwards, were included. RESULTS: Twelve retrospective studies were included. Four studies reported survival outcomes for rectal cancer, two for colon cancer and six as colorectal. Survival outcomes for 356 patients were included. Average 5-year overall survival (OS) was 22.4%, 33.9% and 37.7% in the rectal, colon and colorectal groups respectively. Three year OS in the groups was 53.6%, 46.2% and 65.7%. CONCLUSION: There remains a lack of quality data to confidently make recommendations regarding the management of synchronous PALNM in colon and rectal cancer cohorts. Retrospective data suggests a benefit in highly selective cohorts and therefore a case-by-case evaluation remains the standard of care.


Subject(s)
Colonic Neoplasms , Rectal Neoplasms , Humans , Lymphatic Metastasis/pathology , Retrospective Studies , Lymph Nodes/surgery , Lymph Nodes/pathology , Lymph Node Excision , Colonic Neoplasms/pathology , Rectal Neoplasms/pathology
3.
Int J Colorectal Dis ; 37(2): 437-447, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35037077

ABSTRACT

PURPOSE: Radiotherapy is being used increasingly in the treatment of prostate cancer. However, ionising radiation may confer a small risk of a radiation-induced secondary malignancy. We aim to assess the risk of rectal cancer following pelvic radiotherapy for prostate cancer. METHODS: A search was conducted of the PubMed/MEDLINE, EMBASE and Web of Science databases identifying studies reporting on the risk of rectal cancer following prostatic radiotherapy. Studies must have included an appropriate control group of non-irradiated prostate cancer patients. A meta-analysis was performed to assess the risk of prostatic radiotherapy on subsequent rectal cancer diagnosis. RESULTS: In total, 4757 articles were screened with eight studies meeting the predetermined criteria. A total of 796,386 patients were included in this meta-analysis which showed an increased odds ratio (OR) for subsequent rectal cancer in prostate cancer patients treated with radiotherapy compared to those treated by non-radiotherapy means (OR 1.45, 1.07-1.97, p = 0.02). CONCLUSION: These findings confirm that prostate radiotherapy significantly increases the risk of subsequent rectal cancer. This risk has implications for treatment selection, surveillance and patient counselling. However, it is crucial that this information is presented in a rational and comprehensible manner that does not disproportionately frighten or deter patients from what might be their most suitable treatment modality.


Subject(s)
Neoplasms, Radiation-Induced , Prostatic Neoplasms , Rectal Neoplasms , Humans , Incidence , Male , Prostate , Prostatic Neoplasms/etiology , Prostatic Neoplasms/radiotherapy , Radiotherapy/adverse effects , Rectal Neoplasms/etiology , Rectal Neoplasms/radiotherapy
4.
Int J Colorectal Dis ; 37(5): 1215-1221, 2022 May.
Article in English | MEDLINE | ID: mdl-35487978

ABSTRACT

AIM: There is a current lack of evidence in the literature to support the routine use of negative pressure wound therapy (NPWT) to reduce the risk of surgical site infections (SSI) in the setting of ileostomy or colostomy reversal. The aim of this study is to examine whether routine NPWT confers a lower rate of SSI than conventional dressings following reversal of ileostomy or colostomy. METHODS: The PRIC study is a randomized, controlled, open-label, multi-centre superiority trial to assess whether routine NPWT following wound closure confers a lower rate of SSI following reversal of ileostomy or colostomy when compared to conventional dressings. Participants will be consecutively identified and recruited. Eligible participants will be randomized in a 1:1 allocation ratio, to receive either the NPWT (PREVENA) dressings or conventional dressings which will be applied immediately upon completion of surgery. PREVENA dressings will remain applied for a duration of 7 days. Surgical wounds will then be examined on post-operative day seven as well as during follow-up appointments in OPD for any evidence of SSI. In the interim, public health nurses (PHN) will provide out-patient support services incorporating wound assessment and care as part of a routine basis. Study investigators will liaise with PHN to gather the relevant data in relation to the time to wound healing. Our primary endpoint is the incidence of SSI within 30 days of stoma reversal. Secondary endpoints include measuring time to wound healing, evaluating wound healing and aesthetics and assessing patient satisfaction. CONCLUSION: The PRIC study will assess whether routine NPWT following wound closure is superior to conventional dressings in the reduction of SSI following reversal of ileostomy or colostomy and ascertain whether routine NPWT should be considered the new standard of care.


Subject(s)
Negative-Pressure Wound Therapy , Surgical Wound , Colostomy/adverse effects , Humans , Ileostomy/adverse effects , Multicenter Studies as Topic , Negative-Pressure Wound Therapy/adverse effects , Negative-Pressure Wound Therapy/methods , Randomized Controlled Trials as Topic , Surgical Wound/complications , Surgical Wound/therapy , Surgical Wound Infection/epidemiology , Surgical Wound Infection/etiology , Surgical Wound Infection/prevention & control
5.
Colorectal Dis ; 24(7): 811-820, 2022 07.
Article in English | MEDLINE | ID: mdl-35194919

ABSTRACT

AIM: In low rectal cancers without sphincter involvement a permanent stoma can be avoided without compromising oncological safety. Functional outcomes following coloanal anastomosis (CAA) compared to abdominoperineal excision (APR) may be significantly different. This study examines all available comparative quality of life (QoL) data for patients undergoing CAA versus APR for low rectal cancer. METHODS: Published studies with comparative data on QoL outcomes following CAA versus APR for low rectal cancer were extracted from electronic databases. The study was registered with PROSPERO and adhered to PRISMA (Preferred Reporting Items in Systematic Reviews and Meta-analyses) guidelines. Data was combined using random-effects models. RESULTS: Seven comparative series examined QoL in 527 patients. There was no difference in the numbers receiving neoadjuvant radiotherapy in the APR and CAA groups (OR: 1.19, 95% CI: 0.78-1.81, p = 0.43). CAA was associated with higher mean scores for physical functioning(std mean diff -7.08, 95% CI: -11.92 to -2.25, p = 0.004) and body image (std. mean diff 11.11, 95% CI: 6.04-16.18, p < 0.0001). Male sexual problems were significantly increased in patients who had undergone APR compared to CAA (std. mean diff -16.20, 95% CI: -25.76 to -6.64, p = 0.0009). Patients who had an APR reported more fatigue, dyspnoea and appetite loss. Those who had a CAA reported higher scores for both constipation and diarrhoea. DISCUSSION: It is reasonable to offer a CAA to motivated patients where oncological outcomes will not be threatened. QoL outcomes appear to be superior when intestinal continuity is maintained, and permanent stoma avoided.


Subject(s)
Proctectomy , Rectal Neoplasms , Sexually Transmitted Diseases , Anal Canal/surgery , Anastomosis, Surgical/adverse effects , Humans , Male , Proctectomy/adverse effects , Quality of Life , Rectal Neoplasms/complications , Rectal Neoplasms/surgery , Sexually Transmitted Diseases/complications , Treatment Outcome
6.
Langenbecks Arch Surg ; 407(8): 3193-3200, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36331615

ABSTRACT

BACKGROUND: Primary mucosal anorectal malignant melanoma (AMM) is an invasive malignancy with poor survival. Management options have been variable, due to limited data and lack of randomised control trials available on the optimal surgical strategy. The aim of this review was to compare local excision versus radical resection. METHODS: A systematic search of articles in PubMed, Ovid, Scopus, and the Cochrane Library database was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The outcomes of interest were the impact that surgical strategy had on survival (primary) and recurrence rates (secondary) for the treatment of AMM, comparing sphincter sparing local excision (LE) versus extensive abdominoperineal resection (APR). RESULTS: Ten studies met the predefined criteria. Overall, there were 303 patients, with a median age of 58.2 years. Sixty-one percent (n = 187/303) had radical surgery (abdominoperineal resection) for the primary treatment of AMM. Overall, 5-year survival for the APR and LE was 23% and 32% respectively. Meta-analysis on the median OS noted no statistical difference between the two groups. However, local recurrence occurred in 20.82% and 47.04% in the APR and LE groups respectively. Meta-analysis observed a statistically significant reduction in recurrence when patients had an APR as primary treatment (OR 0.15, 95% CI = 0.08-0.28, p < 0.00001). CONCLUSION: Though local recurrence rates are more common with local excision of AMM, this does not confer an inferior OS when comparing LE versus APR. The decision to proceed with LE vs. APR should be made on a case-by-case basis.


Subject(s)
Anus Neoplasms , Melanoma , Rectal Neoplasms , Humans , Middle Aged , Anus Neoplasms/surgery , Anus Neoplasms/pathology , Rectal Neoplasms/pathology , Anal Canal , Organ Sparing Treatments , Melanoma/surgery , Melanoma/pathology , Melanoma, Cutaneous Malignant
7.
Int J Colorectal Dis ; 36(9): 1819-1829, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33796958

ABSTRACT

PURPOSE: Anastomotic leak (AL) following colorectal cancer resection is associated with considerable morbidity and mortality with an impact on recurrence rates and survival. The impact of obesity on AL rates is debated. This meta-analysis aims to investigate the relationship between obesity and AL. METHODS: A search was conducted of the PubMed/MEDLINE, and Web of Science databases and included studies were split into Western and Asian groups based on population-specific body mass index (BMI) ranges for obesity. A meta-analysis was performed to assess the impact of obesity on AL rate following colorectal cancer resection. RESULTS: Two thousand three hundred and four articles were initially screened. Thirty-one studies totaling 32,953 patients were included. Patients with obesity had a statistically significant increase in AL rate in all Western and Asian study groups. However, this increase was only clinically significant in the rectal anastomotic subgroups-Western: 10.8% vs 8.4%, OR 1.57 (1.01-2.44) and Asian: 9.4% vs 7.4%, OR 1.58 (1.07-2.32). CONCLUSIONS: The findings of this analysis confirm that obesity is a significant risk factor for anastomotic leak, particularly in rectal anastomoses. This effect is thought to be primarily mediated via technical difficulties of surgery although metabolic and immunological factors may also play a role. Obesity in patients undergoing restorative CRC resection should be discussed and considered as part of the pre-operative counselling.


Subject(s)
Anastomotic Leak , Colorectal Neoplasms , Anastomosis, Surgical , Anastomotic Leak/etiology , Colorectal Neoplasms/surgery , Humans , Obesity/complications , Rectum
8.
BMC Cancer ; 20(1): 952, 2020 Oct 02.
Article in English | MEDLINE | ID: mdl-33008336

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is the second most common cause of cancer-related mortality worldwide with one in every five patients diagnosed with metastatic CRC (mCRC). In mCRC cases, the 5-year survival rate remains at approximately 14%, reflecting the lack of effectiveness of currently available treatments such as the anti-VEGF targeting antibody Bevacizumab combined with the chemotherapy folinic acid, fluorouracil and oxaliplatin (FOLFOX). Approximately 60% of patients do not respond to this combined treatment. Furthermore, Bevacizumab inhibits dendritic cell (DC) maturation in poor responders, a key process for tumor eradication. METHOD: Following drug treatment, secreted expression levels of angiogenic and inflammatory markers in tumor conditioned media generated from human ex vivo colorectal tumors were measured by ELISA. Dendritic cell phenotypic and maturation markers were assessed by flow cytometry. RESULTS: Our novel compound, 1,4-dihydroxy quininib, acts in an alternative pathway compared to the approved therapy Bevacizumab. 1,4-dihydroxy quininib alone, and in combination with Bevacizumab or FOLFOX significantly reduced TIE-2 expression which is involved in the promotion of tumor vascularization. Combination treatment with 1,4-dihydroxy quininib significantly increased the expression level of DC phenotypic and maturation markers. CONCLUSION: Our results indicate the anti-angiogenic small molecule 1,4-dihydroxy quininib could be an alternative novel treatment in combination therapy for CRC patients.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Colorectal Neoplasms/drug therapy , Aged , Aged, 80 and over , Angiogenesis Inhibitors/pharmacology , Angiopoietin-2/metabolism , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bevacizumab/administration & dosage , Bevacizumab/pharmacology , Colorectal Neoplasms/blood supply , Colorectal Neoplasms/metabolism , Female , Fluorouracil/administration & dosage , Fluorouracil/pharmacology , Humans , Leucovorin/administration & dosage , Leucovorin/pharmacology , Male , Middle Aged , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/pharmacology , Phenols/administration & dosage , Phenols/pharmacology , Quinolines/administration & dosage , Quinolines/pharmacology , Tumor Cells, Cultured
9.
Breast Cancer Res Treat ; 161(2): 289-297, 2017 01.
Article in English | MEDLINE | ID: mdl-27878392

ABSTRACT

PURPOSE: Electrochemotherapy (ECT) is the application of electric pulses to tumour tissue to render the cell membranes permeable to usually impermeant hydrophilic anti-cancer drugs, thereby enhancing cytotoxic effects. We sought to ascertain whether ECT can be an effective palliative treatment for cutaneous metastases of breast cancer. METHODS: This work reports data from the European Standard Operating Procedures for Electrochemotherapy trial (EudraCT Number: 2004-002183-18). In combination with systemic and/or intratumoural bleomycin, optimised electric pulses were delivered to locally recurrent or metastatic cutaneous breast cancer lesions. Follow-up continued until December 2014. RESULTS: Between February 2004 and December 2014, twenty-four patients were treated. All patients had received prior multimodal therapy. In total, the patient cohort had, or developed, 242 lesions. Two hundred and 36 lesions were treated, with 34 lost to follow-up. An objective response was seen in 161 of 202 lesions (79.7%), with a complete response observed in 130 (64.3%). Thirty-nine lesions (19.3%) did not respond, while 2 (1%) progressed following ECT. 17 (73.9%) patients received two or fewer treatments. A minimum of a partial response was seen in at least 50% of treated lesions in 18 of the 24 (75%) patients. Smaller lesions were more likely to have an objective response (Chi-square test for trend, p < 0.001). CONCLUSIONS: Electrochemotherapy is an effective treatment for cutaneous breast cancer lesions that have proven refractory to standard therapies. As smaller lesions were found to be more responsive, we suggest that ECT should be considered as an early treatment modality, within multimodal treatment strategies.


Subject(s)
Antineoplastic Agents/therapeutic use , Breast Neoplasms/pathology , Skin Neoplasms/drug therapy , Skin Neoplasms/secondary , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Bleomycin/administration & dosage , Bleomycin/adverse effects , Bleomycin/therapeutic use , Breast Neoplasms/mortality , Breast Neoplasms/therapy , Combined Modality Therapy , Female , Humans , Middle Aged , Skin Neoplasms/diagnosis , Skin Neoplasms/mortality , Treatment Outcome , Tumor Burden
10.
Am Surg ; 90(3): 445-454, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37972216

ABSTRACT

INTRODUCTION: The management of anal cancer relies on clinical and histopathological features for treatment decisions. In recent years, the field of radiomics, which involves the extraction and analysis of quantitative imaging features, has shown promise in improving management of pelvic cancers. The aim of this study was to evaluate the current application of radiomics in the management of anal cancer. METHODS: A systematic search was conducted in Medline, EMBASE, and Web of Science databases. Inclusion criteria encompassed randomized and non-randomized trials investigating the use of radiomics to predict post-operative recurrence in anal cancer. Study quality was assessed using the QUADAS-2 and Radiomics Quality Score tools. RESULTS: The systematic review identified a total of nine studies, with 589 patients examined. There were three main outcomes assessed in included studies: recurrence (6 studies), progression-free survival (2 studies), and prediction of human papillomavirus (HPV) status (1 study). Radiomics-based risk stratification models were found to provide valuable insights into treatment response and patient outcomes, with all developed signatures demonstrating at least modest accuracy (range: .68-1.0) in predicting their primary outcome. CONCLUSION: Radiomics has emerged as a promising tool in the management of anal cancer. It offers the potential for improved risk stratification, treatment planning, and response assessment, thereby guiding personalized therapeutic approaches.


Subject(s)
Anus Neoplasms , Radiomics , Humans , Anus Neoplasms/diagnostic imaging , Anus Neoplasms/therapy , Databases, Factual , Postoperative Period
11.
Curr Oncol ; 31(9): 5151-5163, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39330009

ABSTRACT

BACKGROUND: We aim to ascertain prognostic factors in the current management of anal cancer within this study. METHODS: We reviewed the management and outcomes of anal cancer cases over a seven-year period, inclusive (2016-2023). The primary objectives were to assess the demographic characteristics, clinical presentation, and outcomes of all anal cancer patients within our institution. Kaplan-Meier survival analysis was used to estimate survival differences between cohorts, with statistical significance determined using log-rank testing. Cox proportional hazards regression was utilised to identify prognostic factors. Cox regression hazard ratios were reported along with confidence intervals and p-values. RESULTS: The median follow-up time for the study was 29.8 months. Seventy-five patients with anal cancer were included in this study, with 88% (66/75) being squamous cell carcinoma (SCC) and the majority having regional disease (82.7% (62/75)). The median age at diagnosis was 63.4 years (36-94). There was a female preponderance (57.3% (43/75)). In total, 84% (63/75) underwent definitive chemoradiation (dCRT), with 7/63 (11.1%) requiring a salvage abdomino-perineal resection (APR) for residual or recurrent disease. Adverse prognostic indicators include those with T4 disease hazard ratio = 3.81, (95% CI 1.13-12.83, * p = 0.04), poorly differentiated tumour disease HR = 3.37, (95% CI 1.13-10.02, * p = 0.04), having N2 nodal status HR = 5.03, (95% CI 1.11-22.8, * p = 0.04), and having metastatic disease at diagnosis HR = 5.8, (95% CI 1.28-26.42, * p = 0.02). CONCLUSION: Presenting characteristics including stage, nodal, and differentiation status remain key prognostic indicators in those diagnosed with anal malignancy.


Subject(s)
Anus Neoplasms , Humans , Anus Neoplasms/therapy , Anus Neoplasms/mortality , Female , Male , Middle Aged , Aged , Adult , Aged, 80 and over , Prognosis , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/mortality , Chemoradiotherapy/methods , Retrospective Studies , Kaplan-Meier Estimate , Treatment Outcome
12.
Diagnostics (Basel) ; 14(16)2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39202258

ABSTRACT

INTRODUCTION: Goblet cell carcinoid (GCC) is a rare and poorly understood appendiceal neoplasm, exhibiting mixed histological and aggressive clinical features. Current guidelines recommend right hemicolectomy in all cases, although there is conflicting evidence that appendicectomy alone may be sufficient. This review aims to identify the optimal surgical management for appendiceal GCC. METHODS: A systematic review was performed by searching MEDLINE, Embase, Scopus and the Cochrane Register of Controlled Trials. Randomised controlled trials, cohort studies or large case series (>5 patients) reporting clinical outcomes for patients undergoing surgical management of GCC of the appendix were included. Outcomes extracted included participant and tumour characteristics, type of surgery and survival data. RESULTS: A total of 1341 studies were retrieved. After duplicate removal, 796 titles were screened for relevance prior to abstract and full text review. A total of six studies were included for analysis, comprising 3177 patients-1629 females and 1548 males. The median age ranged from 51 to 72 years. A total of 2329 patients underwent right hemicolectomy, while 824 were treated with appendicectomy only. Overall, the included studies report increased survival in patients undergoing right hemicolectomy compared to appendicectomy alone. A meta-analysis was not possible due to insufficient data reported in the published literature to date. CONCLUSIONS: There is no consensus regarding the optimal surgical management of appendiceal GCC, as outcomes-based data comparing surgical interventions are lacking. It is possible that some patients with favourable features are overtreated. The absence of robust evidence to support a more conservative approach means that right hemicolectomy remains the standard of care for all patients, in keeping with current international guidelines. The rarity of this condition and limited data in the published studies remain barriers to evidence-based best clinical practice.

13.
Ir J Med Sci ; 193(4): 1721-1728, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38532236

ABSTRACT

PURPOSE/AIM: Perianal wound healing and/or complications are common following abdominoperineal resection (APR). Although primary closure is commonly undertaken, myocutaneous flap closure such as vertical rectus abdominis myocutaneous flap (VRAM) is thought to improve wound healing process and outcome. A comprehensive meta-analysis was performed to compare outcomes of primary closure versus VRAM flap closure of perineal wound following APR. METHODS: PubMed, MEDLINE, EMBASE, and Cochrane Central Registry of Controlled Trials were comprehensively searched until the 8th of August 2023. Included studies underwent meta-analysis to compare outcomes of primary closure versus VRAM flap closure of perineal wound following APR. The primary outcome of interest was perineal wound complications, and the secondary outcomes were abdominal wound complications, dehiscence, wound healing time, length of hospital stay, and mortality. RESULTS: Ten studies with 1141 patients were included. Overall, 853 patients underwent primary closure (74.8%) and 288 patients underwent VRAM (25.2%). Eight studies reported on perineal wound complications after APR: 38.2% (n = 263/688) in the primary closure group versus 32.8% (n = 80/244) in the VRAM group. Perineal complication rates were statistically significantly lower in the VRAM group versus primary closure ((M-H OR, 1.61; 95% CI 1.04-2.49;


Subject(s)
Myocutaneous Flap , Perineum , Rectus Abdominis , Wound Healing , Humans , Perineum/surgery , Proctectomy/methods , Proctectomy/adverse effects , Postoperative Complications , Length of Stay/statistics & numerical data
14.
Cancer Lett ; 604: 217253, 2024 Nov 01.
Article in English | MEDLINE | ID: mdl-39278399

ABSTRACT

Resistance to neoadjuvant chemoradiation therapy (neo-CRT) is a significant clinical problem in the treatment of locally advanced rectal cancer. Identification of novel therapeutic targets and biomarkers predicting therapeutic response is required to improve patient outcomes. Increasing evidence supports a role for the complement system in resistance to anti-cancer therapy. In this study, increased expression of complement effectors C3 and C5 and increased production of anaphylatoxins, C3a and C5a, was observed in radioresistant rectal cancer cells. Modulation of the central complement effector, C3, was demonstrated to functionally alter the radioresponse, with C3 overexpression significantly enhancing radioresistance, whilst C3 inhibition significantly increased sensitivity to a clinically-relevant dose of radiation. Inhibition of C3 was demonstrated to increase DNA damage and alter cell cycle distribution, mediating a shift towards a radiosensitive cell cycle phenotype suggesting a role for C3 in reprogramming of the tumoural radioresponse. Expression of the complement effectors C3 and C5 was significantly increased in human rectal tumour tissue, as was expression of CFB, a component of the alternative pathway of activation. Elevated levels of C3a and C5b-9 in pre-treatment sera from rectal cancer patients was associated with subsequent poor responses to neo-CRT and poorer survival. Together these data demonstrate a role for complement in the radioresistance of rectal cancer and identify key complement components as potential biomarkers predicting response to neo-CRT and outcome in rectal cancer.


Subject(s)
Radiation Tolerance , Rectal Neoplasms , Humans , Rectal Neoplasms/pathology , Rectal Neoplasms/radiotherapy , Rectal Neoplasms/metabolism , Rectal Neoplasms/genetics , Cell Line, Tumor , Complement C3/metabolism , Neoadjuvant Therapy/methods , DNA Damage , Complement C3a/metabolism , Cell Cycle , Chemoradiotherapy, Adjuvant
15.
Ir J Med Sci ; 2023 Nov 09.
Article in English | MEDLINE | ID: mdl-37943400

ABSTRACT

BACKGROUND: Mean corpuscular volume (MCV) has been shown to have some correlation to oncological outcomes in oesophageal cancer, with high pre-operative MCV associated with disease recurrence. A similar association has previously been reported in colorectal cancer. AIMS: This study is aimed at investigating whether high MCV bears similar relation to post-operative outcome and disease recurrence in colorectal cancer (CRC). METHODS: Patients undergoing elective CRC resection with curative intent between January 2008 and December 2019 were identified from our prospective database. Review of patient demographic details, American Society of Anaesthesiologists (ASA) grade, smoking and alcohol intake were performed. In addition, tumour location and staging, operation performed, pre-operative laboratory data and oncological management of each patient were noted. Post-operative morbidity (Clavien-Dindo (CD) score > 2), 30-day mortality, in-hospital mortality and cancer recurrence were examined and multivariable regression analysis was performed to predict these outcomes. RESULTS: A total of 1,293 CRCs were resected, with 1,159 patients (89.7%) experiencing a hospital course without major morbidity (CD < 3). 30-day mortality rate was less than 1% (12/1293). There were 176 patients (13.6%) with recurrence at follow-up. When multivariable regression analysis was performed, high pre-operative MCV did not predict negative post-operative or oncological outcomes. CONCLUSION: MCV does not appear to be an independent prognostic factor for outcomes following elective CRC resection.

16.
Cancers (Basel) ; 15(24)2023 Dec 12.
Article in English | MEDLINE | ID: mdl-38136361

ABSTRACT

Radiogenomics, a sub-domain of radiomics, refers to the prediction of underlying tumour biology using non-invasive imaging markers. This novel technology intends to reduce the high costs, workload and invasiveness associated with traditional genetic testing via the development of 'imaging biomarkers' that have the potential to serve as an alternative 'liquid-biopsy' in the determination of tumour biological characteristics. Radiogenomics also harnesses the potential to unlock aspects of tumour biology which are not possible to assess by conventional biopsy-based methods, such as full tumour burden, intra-/inter-lesion heterogeneity and the possibility of providing the information of tumour biology longitudinally. Several studies have shown the feasibility of developing a radiogenomic-based signature to predict treatment outcomes and tumour characteristics; however, many lack prospective, external validation. We performed a systematic review of the current literature surrounding the use of radiogenomics in rectal cancer to predict underlying tumour biology.

17.
Front Oncol ; 13: 1216911, 2023.
Article in English | MEDLINE | ID: mdl-37601689

ABSTRACT

Resistance to neoadjuvant chemoradiation therapy, is a major challenge in the management of rectal cancer. Increasing evidence supports a role for altered energy metabolism in the resistance of tumours to anti-cancer therapy, suggesting that targeting tumour metabolism may have potential as a novel therapeutic strategy to boost treatment response. In this study, the impact of metformin on the radiosensitivity of colorectal cancer cells, and the potential mechanisms of action of metformin-mediated radiosensitisation were investigated. Metformin treatment was demonstrated to significantly radiosensitise both radiosensitive and radioresistant colorectal cancer cells in vitro. Transcriptomic and functional analysis demonstrated metformin-mediated alterations to energy metabolism, mitochondrial function, cell cycle distribution and progression, cell death and antioxidant levels in colorectal cancer cells. Using ex vivo models, metformin treatment significantly inhibited oxidative phosphorylation and glycolysis in treatment naïve rectal cancer biopsies, without affecting the real-time metabolic profile of non-cancer rectal tissue. Importantly, metformin treatment differentially altered the protein secretome of rectal cancer tissue when compared to non-cancer rectal tissue. Together these data highlight the potential utility of metformin as an anti-metabolic radiosensitiser in rectal cancer.

18.
Cancers (Basel) ; 15(18)2023 Sep 08.
Article in English | MEDLINE | ID: mdl-37760439

ABSTRACT

INTRODUCTION: Historically, surgical resection for patients with locally recurrent rectal cancer (LRRC) had been reserved for those without metastatic disease. 'Selective' patients with limited oligometastatic disease (OMD) (involving the liver and/or lung) are now increasingly being considered for resection, with favourable five-year survival rates. METHODS: A retrospective analysis of consecutive patients undergoing multi-visceral pelvic resection of LRRC with their oligometastatic disease between 1 January 2015 and 31 August 2021 across four centres worldwide was performed. The data collected included disease characteristics, neoadjuvant therapy details, perioperative and oncological outcomes. RESULTS: Fourteen participants with a mean age of 59 years were included. There was a female preponderance (n = 9). Nine patients had liver metastases, four had lung metastases and one had both lung and liver disease. The mean number of metastatic tumours was 1.5 +/- 0.85. R0 margins were obtained in 71.4% (n = 10) and 100% (n = 14) of pelvic exenteration and oligometastatic disease surgeries, respectively. Mean lymph node yield was 11.6 +/- 6.9 nodes, with positive nodes being found in 28.6% (n = 4) of cases. A single major morbidity was reported, with no perioperative deaths. At follow-up, the median disease-free survival and overall survival were 12.3 months (IQR 4.5-17.5 months) and 25.9 months (IQR 6.2-39.7 months), respectively. CONCLUSIONS: Performing radical multi-visceral surgery for LRRC and distant oligometastatic disease appears to be feasible in appropriately selected patients that underwent good perioperative counselling.

19.
Ir J Med Sci ; 191(3): 1291-1295, 2022 Jun.
Article in English | MEDLINE | ID: mdl-34327621

ABSTRACT

BACKGROUND: Acute sigmoid volvulus (ASV) represents a small but significant portion of cases of large bowel obstruction, especially in the elderly and co-morbid. Given the characteristics of the patient cohort most commonly affected, a non-operative/conservative approach is often undertaken but is associated with a high rate of recurrence. OBJECTIVE: We sought to evaluate outcomes for those patients who underwent non-operative management, emergency surgery or staged, semi-elective surgery following decompression for ASV at our institution. METHODS: Hospital in-patient enquiry (HIPE) data were used to identify all patients who presented with sigmoid volvulus between January 2005 and June 2020 inclusive. Patient notes were interrogated, including surgical and endoscopic procedures performed. Patient demographics and co-morbidities were recorded. RESULTS: Thirty-nine patients were treated over a 15-year period with a mean age of 73 years at first presentation (range 36-93). Twenty-two patients (56%) had just a single admission for ASV with three deaths in this group. Seventeen patients (44%) had more than one admission with volvulus due to recurrence after a decompression-only strategy on the index admission. Of these, three succumbed to complications of their subsequent episodes of volvulus. Twenty-five patients underwent surgical intervention (fifteen on, or shortly following, their first admission and ten following at least two admissions for ASV). The overall mortality in the operative group was 2/25 (8%) with both deaths in those undergoing emergency surgeries. Five patients were treated successfully with endoscopic measures alone and had required no further interventions at the time of compiling data. CONCLUSION: There is a high recurrence rate following non-operative management of acute sigmoid volvulus and consequently, a cumulative increase in the attendant significant morbidity and mortality with subsequent episodes. Given the relatively low complication rate of definitive surgery, even in those patients perceived to be high risk, we contend that all patients should be considered for early surgery to prevent the likely recurrence of sigmoid volvulus.


Subject(s)
Intestinal Volvulus , Sigmoid Diseases , Aged , Cohort Studies , Elective Surgical Procedures , Humans , Intestinal Volvulus/surgery , Retrospective Studies , Sigmoid Diseases/surgery
20.
Curr Oncol ; 30(1): 416-429, 2022 12 28.
Article in English | MEDLINE | ID: mdl-36661683

ABSTRACT

Background: Rectal gastrointestinal stromal tumours (GISTs) have many treatment options, but uncertainty remains regarding the best treatment regimen for this rare pathology. The aim of this review is to assess the optimal management approach including timing of chemotherapy. Methods: PubMed, EMBASE, and Cochrane databases were searched for relevant articles comparing the impact of radical vs. local excision, and neoadjuvant vs. adjuvant therapy had on outcomes in the management of rectal GISTs. We specifically evaluated the influence that the aforementioned factors had on margins, recurrence, overall survival, 5-year disease-free survival, and hospital length of stay. Results: Twenty-eight studies met our predefined criteria and were included in our study, twelve of which were included in the quantitative synthesis. When comparing neoadjuvant versus adjuvant chemotherapy, our meta-analysis noted no significance in terms of margin negativity (R0) (odds ratio [OR] 2.01, 95% confidence interval [CI], 0.7−5.79, p = 0.20) or recurrence rates (OR 0.22, 95% CI, 0.02−1.91, p = 0.17). However, there was a difference in overall 5-year survival in favour of neoadjuvant therapy (OR 3.19, 95% CI, 1.37−7.40, * p = 0.007). Comparing local excision versus radical excision, our meta-analysis observed no significance in terms of overall 5-year survival (OR1.31, 95% CI, 0.81−2.12, p = 0.26), recurrence (OR 0.67, 95% CI, 0.40−1.13, p = 0.12), or 5-year disease-free survival (OR 1.10, 95% CI, 0.55−2.19, p = 0.80). There was a difference in length of hospital stay with a reduced mean length of stay in local excision group (mean difference [MD] 6.74 days less in the LE group; 95% CI, −6.92−−6.56, * p =< 0.00001) as well as a difference in R0 rates in favour of radical resection (OR 0.68, 95% CI, 0.47−0.99, * p = 0.05). Conclusion: Neoadjuvant chemotherapy is associated with improved overall 5-year survival, while local excision is associated with reduced mean length of hospital stay. Further large-volume, prospective studies are required to further define the optimal treatment regimen in this complex pathology.


Subject(s)
Gastrointestinal Stromal Tumors , Rectal Neoplasms , Humans , Rectum/pathology , Rectum/surgery , Gastrointestinal Stromal Tumors/surgery , Rectal Neoplasms/surgery , Rectal Neoplasms/pathology , Disease-Free Survival , Combined Modality Therapy
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