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3.
Eur J Surg Oncol ; 50(1): 107268, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38043361

ABSTRACT

Intestinal lymphomas can rarely present as abdominal catastrophes with perforation or small bowel obstruction. There is little data regarding their optimal surgical management and associated outcomes. We aimed to systematically review relevant published literature to assess the presentation, diagnosis, optimal surgical approach and associated post-operative outcomes. A systematic on-line literature search of Embase and Medline identified 1485 articles of which 34 relevant studies were selected, including 7 retrospective studies, 1 case series and 26 case reports. Selected articles were assessed by two reviewers to extract data. 95 patients with abdominal catastrophes secondary to lymphoma (predominately Burkitt (28 %) and Diffuse Large B-cell lymphoma (29 %)) were identified with a median age of 52 years, 40 % were female. Of the small bowel resections 25% (n = 18) suffered post-operative complications with a 13.8 % (n = 10) 30-day mortality. Ileocolonic resections had a 27 % complication rate with 18 % mortality and primary repair had a 25 % complications rate and 25 % mortality. Median follow-up was 8 days (range 1-96). Notable points of differences in the presentations between these different lymphomas included the majority of Burkitt's lymphoma were younger, had a known diagnosis, were on chemotherapy and presented with perforation in contrast to those with B cell lymphoma who were predominately older, had new diagnoses and presented with a balanced proportion of obstruction and perforation. Abdominal catastrophes secondary to intestinal lymphomas most commonly present with perforation. Aggressive surgical management, including small bowel resection, may offer similar remission rates for lymphoma patients presenting with abdominal catastrophes as those without such emergency complications.


Subject(s)
Burkitt Lymphoma , Intestinal Neoplasms , Intestinal Obstruction , Lymphoma , Humans , Female , Middle Aged , Male , Laparotomy , Retrospective Studies , Lymphoma/complications , Lymphoma/surgery , Burkitt Lymphoma/complications , Burkitt Lymphoma/diagnosis , Burkitt Lymphoma/surgery , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Intestinal Neoplasms/complications , Intestinal Neoplasms/surgery
4.
Br J Surg ; 110(11): 1535-1542, 2023 Oct 10.
Article in English | MEDLINE | ID: mdl-37611141

ABSTRACT

BACKGROUND: Surgical errors are acts or omissions resulting in negative consequences and/or increased operating time. This study describes surgeon-reported errors in laparoscopic cholecystectomy. METHODS: Intraoperative videos were uploaded and annotated on Touch SurgeryTM Enterprise. Participants evaluated videos for severity using a 10-point intraoperative cholecystitis grading score, and errors using Observational Clinical Human Reliability Assessment, which includes skill, consequence, and mechanism classifications. RESULTS: Nine videos were assessed by 8 participants (3 junior (specialist trainee (ST) 3-5), 2 senior trainees (ST6-8), and 3 consultants). Participants identified 550 errors. Positive relationships were seen between total operating time and error count (r2 = 0.284, P < 0.001), intraoperative grade score and error count (r2 = 0.578, P = 0.001), and intraoperative grade score and total operating time (r2 = 0.157, P < 0.001). Error counts differed significantly across intraoperative phases (H(6) = 47.06, P < 0.001), most frequently at dissection of the hepatocystic triangle (total 282; median 33.5 (i.q.r. 23.5-47.8, range 15-63)), ligation/division of cystic structures (total 124; median 13.5 (i.q.r. 12-19.3, range 10-26)), and gallbladder dissection (total 117; median 14.5 (i.q.r. 10.3-18.8, range 6-26)). There were no significant differences in error counts between juniors, seniors, and consultants (H(2) = 0.03, P = 0.987). Errors were classified differently. For dissection of the hepatocystic triangle, thermal injuries (50 in total) were frequently classified as executional, consequential errors; trainees classified thermal injuries as step done with excessive force, speed, depth, distance, time or rotation (29 out of 50), whereas consultants classified them as incorrect orientation (6 out of 50). For ligation/division of cystic structures, inappropriate clipping (60 errors in total), procedural errors were reported by junior trainees (6 out of 60), but not consultants. For gallbladder dissection, inappropriate dissection (20 errors in total) was reported in incorrect planes by consultants and seniors (6 out of 20), but not by juniors. Poor economy of movement (11 errors in total) was reported more by consultants (8 out of 11) than trainees (3 out of 11). CONCLUSION: This study suggests that surgical experience influences error interpretation, but the benefits for surgical training are currently unclear.


Subject(s)
Cholecystectomy, Laparoscopic , Humans , Cholecystectomy, Laparoscopic/methods , Dissection , Gallbladder , Ligation , Reproducibility of Results
5.
J Surg Educ ; 80(7): 994-1004, 2023 07.
Article in English | MEDLINE | ID: mdl-37164903

ABSTRACT

OBJECTIVE: This study compares the intraoperative phase times in laparoscopic cholecystectomy performed by an attending surgeon and supervised residents over 10-years to assess operative times as a marker of performance and any impact of case severity on times. DESIGN: Laparoscopic cholecystectomy videos were uploaded to Touch Surgery™ Enterprise, a combined software and hardware solution for securely recording, storing, and analysing surgical videos, which provide analytics of intraoperative phase times. Case severity and visualisation of the critical view of safety (CVS) were manually assessed using modified 10-point intraoperative gallbladder scoring system (mG10) and CVS scores, respectively. Attending and residents' times were compared unmatched and matched by mG10. SETTING: Secondary analysis of anonymized laparoscopic cholecystectomy video, recorded as standard of care. PARTICIPANTS: Adult patients who underwent elective laparoscopic cholecystectomy a single UK hospital. Cases were performed by one attending and their residents. RESULTS: 159 (attending=96, resident=63) laparoscopic cholecystectomy videos and intraoperative phase times were reviewed on Touch Surgery™ Enterprise and analyzed. Attending cases were more challenging (p=0.037). Residents achieved higher CVS scores (p=0.034) and showed longer dissection of hepatocystic triangle (HCT) times (p=0.012) in more challenging cases. Residents' total operative time (p=0.001) and dissection of HCT (p=0.002) times exceeded the attending's in low-severity matched cases (mG10=1). Residents' total operative times (p<0.001), port insertion/gallbladder exposure (p=0.032), and dissection of HCT (p<0.001) exceeded the attending's in matched cases (mG10=2). Residents' total operative (p<0.001), dissection of HCT (p<0.001), and gallbladder dissection (p=0.010) times exceeded the attendings in unmatched cases. CONCLUSIONS: Residents' total operative and dissection of HCT times significantly exceeded the attending's unmatched cases and low-severity matched cases which could suggest training need, however, also reflects an expected assessment of competence, and validates time as a marker of performance.


Subject(s)
Cholecystectomy, Laparoscopic , Internship and Residency , Surgeons , Adult , Humans , Cholecystectomy, Laparoscopic/education , Dissection
7.
BJS Open ; 6(4)2022 07 07.
Article in English | MEDLINE | ID: mdl-35849132

ABSTRACT

BACKGROUND: Simulation training can improve the learning curve of surgical trainees. This research aimed to systematically review randomized clinical trials (RCT) evaluating the performance of junior surgical trainees following virtual reality training (VRT) and other training methods in laparoscopic cholecystectomy. METHODS: MEDLINE (PubMed), Embase (Ovid SP), Web of Science, Scopus and LILACS were searched for trials randomizing participants to VRT or no additional training (NAT) or simulation training (ST). Outcomes of interest were the reported performance using global rating scores (GRS), the Objective Structured Assessment of Technical Skill (OSATS) and Global Operative Assessment of Laparoscopic Skills (GOALS), error counts and time to completion of task during laparoscopic cholecystectomy on either porcine models or humans. Study quality was assessed using the Cochrane Risk of Bias Tool. PROSPERO ID: CRD42020208499. RESULTS: A total of 351 titles/abstracts were screened and 96 full texts were reviewed. Eighteen RCT were included and 15 manuscripts had data available for meta-analysis. Thirteen studies compared VRT and NAT, and 4 studies compared VRT and ST. One study compared VRT with NAT and ST and reported GRS only. Meta-analysis showed OSATS score (mean difference (MD) 6.22, 95%CI 3.81 to 8.36, P < 0.001) and time to completion of task (MD -8.35 min, 95%CI 13.10 to 3.60, P = <0.001) significantly improved after VRT compared with NAT. No significant difference was found in GOALS score. No significant differences were found between VRT and ST groups. Intraoperative errors were reported as reduced in VRT groups compared with NAT but were not suitable for meta-analysis. CONCLUSION: Meta-analysis suggests that performance measured by OSATS and time to completion of task is improved with VRT compared with NAT for junior trainee in laparoscopic cholecystectomy. However, conclusions are limited by methodological heterogeneity and more research is needed to quantify the potential benefit to surgical training.


Subject(s)
Cholecystectomy, Laparoscopic , Laparoscopy , Simulation Training , Virtual Reality , Animals , Humans , Laparoscopy/education , Randomized Controlled Trials as Topic , Simulation Training/methods , Swine
8.
J Surg Case Rep ; 2021(3): rjab035, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33732426

ABSTRACT

Aorto-oesophageal fistula (AOF) is a life-threatening condition that usually presents with upper gastro-intestinal haemorrhage. This case report details the emergency presentation and management of a 51-year-old male who presented with hematemesis secondary to an impacted denture (ingested two years previously) in the oesophagus that had led to an AOF. This necessitated urgent thoracic endovascular aortic repair followed by thoracotomy, oesophagotomy, T-tube insertion and oesophagostomy. This is the first documentation in the literature of the dual-modality management for this rare cause of AOF and demonstrates the multidisciplinary approach to successful management of this complex yet rare presentation.

9.
J Thorac Cardiovasc Surg ; 160(3): 858-866, 2020 Sep.
Article in English | MEDLINE | ID: mdl-31928822

ABSTRACT

BACKGROUND: ARS has been adopted in select patients with lung transplant for the past 2 decades in many centers. Outcomes have been reported sporadically. No pooled analysis of retrospective series has been performed. OBJECTIVE: This review and pooled analysis sought to demonstrate objective evidence of improved graft function in lung transplant patients undergoing antireflux surgery (ARS). METHODS: In accordance with Meta-analyses of Observational Studies in Epidemiology guidelines, a search of PubMed Central, Medline, Google Scholar, and Cochrane Library databases was performed. Articles documenting spirometry data pre- and post-ARS were reviewed and a random-effects model meta-analysis was performed on forced expiratory volume in 1 second (FEV1) values and the rate of change of FEV1. RESULTS: Six articles were included in the meta-analysis. Regarding FEV1 before and after ARS, we observed a small increase in FEV1 values in studies reporting raw values (2.02 ± 0.89 L/1 sec vs 2.14 ± 0.77 L/1 sec; n = 154) and % of predicted (77.1% ± 22.1% vs 81.2% ± 26.95%; n = 45), with a small pooled Cohen d effect size of 0.159 (P = .114). When considering the rate of change of FEV1 we observed a significant difference in pre-ARS compared with post-ARS (-2.12 ± 2.76 mL/day vs +0.05 ± 1.19 mL/day; n = 103). There was a pooled effect size of 1.702 (P = .013), a large effect of ARS on the rate of change of FEV1 values. CONCLUSIONS: This meta-analysis of retrospective observational studies demonstrates that ARS might benefit patients with declining FEV1, by examining the rate of change of FEV1 during the pre- and postoperative periods.


Subject(s)
Fundoplication/methods , Gastroesophageal Reflux/complications , Gastroesophageal Reflux/surgery , Graft Rejection/prevention & control , Lung Transplantation , Allografts , Bronchiolitis Obliterans/prevention & control , Gastric Acidity Determination , Humans , Hydrogen-Ion Concentration , Respiratory Function Tests
10.
Patient Saf Surg ; 13: 27, 2019.
Article in English | MEDLINE | ID: mdl-31452683

ABSTRACT

BACKGROUND: Morbidity & Mortality (M&M) meetings are a critical component of clinical governance. They have the potential to improve patient outcomes, quality of care, attitudes towards patient safety and they contribute to the education of clinical staff. This study aimed to evaluate individual surgeons' experience of these meetings, and to explore their perceived usefulness and barriers to open discussion of adverse outcomes. METHODS: Consultant general surgeons in London, United Kingdom, were invited to anonymously complete an online survey consisting of 18 key items. RESULTS: Invitations were sent to 323 consultant surgeons from 19 NHS Trusts. Responses were received from 109 (33.7%), of which 99 (90.8%) answered all key items. Seventy-two of 104 (69.2%) attend almost all or all M&M meetings. These were rated as being more conducive for learning than for service improvement (p = 0.001). On a scale of 1 to 10 (10 = fearless), 41 of 105 (39.0%) rated as ≤5 the fearfulness of legal or other negative repercussions resulting from open discussion of complications/mortalities. Ninety-eight respondents gave a median rating of 10 (IQR: 8-10) for willingness to talk openly about their complications/mortalities (10 = willing/able). CONCLUSIONS: Many surgeons in London do not routinely attend M&M meetings, despite these occurring within 'protected time'. There may be a willingness to talk openly about complications, though there exists a fear of litigation. The nature, content and learning potential of such open M&M discussions should be explored in future research.

11.
J Gastrointest Surg ; 22(10): 1785-1794, 2018 10.
Article in English | MEDLINE | ID: mdl-29943138

ABSTRACT

BACKGROUND: Acquired aerodigestive fistulae (ADF) are rare, but associated with a high mortality rate. We present our experience of the diagnosis, management and outcomes of patients with ADFs treated at a tertiary centre. Utilising our findings, we propose an anatomical classification system, demonstrating how specific features of an ADF may determine management. METHODS: A clinical database was searched and 48 patients with an ADF were identified. A classification system was developed based on anatomical location of the ADF and differences in clinico-pathological features based on this categorisation were performed, with the chi-squared test used for inferential analyses and Kaplan-Meier curves with log-rank test to assess survival. RESULTS: Twenty (41.6%) patients developed an ADF secondary to malignancy, with previous radiotherapy (18.7%), post-operative anastomotic dehiscence and endotherapy (14.6% each) representing other causes. Thirty-one patients were managed with tracheal and/or oesophageal stents and eight underwent surgical repair. The classification system demonstrated benign causes of ADF were either proximally or distally sited, whilst a malignant cause resulted in mid-tracheal fistulae (p = 0.001), with the latter associated with poorer survival. ADFs over 20 mm in size were associated with poor survival (p = 0.011), as was the use of previous radiotherapy. Proximal and distal ADFs were associated with improved survival (p = 0.006), as were those patients managed surgically (p = 0.001). CONCLUSION: By classifying ADFs, we have demonstrated that anatomical location correlates with the size, history of malignancy, previous radiotherapy and aetiology of ADF, which can affect management. The proposed classification system will aid in formulating multi-modality individualised treatment plans.


Subject(s)
Neoplasms/complications , Tracheoesophageal Fistula/classification , Tracheoesophageal Fistula/etiology , Adult , Aged , Anastomosis, Surgical/adverse effects , Female , Humans , Male , Middle Aged , Neoplasms/radiotherapy , Postoperative Complications , Radiotherapy/adverse effects , Retrospective Studies , Stents , Survival Rate , Tracheoesophageal Fistula/surgery , Young Adult
12.
J Gastrointest Surg ; 22(8): 1319-1324, 2018 08.
Article in English | MEDLINE | ID: mdl-29667092

ABSTRACT

BACKGROUND: Denervation of the pylorus after oesophagectomy is considered the principal factor responsible for delayed gastric emptying. Several studies have attempted to delineate whether surgical or chemical management of the pylorus during oesophagectomy is of benefit, but with conflicting results. The aim of this multicentre study was to assess whether there was any difference in outcomes between different approaches to management of the pylorus. METHODS: A prospectively maintained database was used to identify patients who underwent oesophagectomy for malignancy. They were divided into separate cohorts based on the specific pyloric intervention: intra-pyloric botulinum toxin injection, pyloroplasty and no pyloric treatment. Main outcome parameters were naso-gastric tube duration and re-siting, endoscopic pyloric intervention after surgery both as in- and outpatient, length of hospital stay, in-hospital mortality and delayed gastric emptying symptoms at first clinic appointment. RESULTS: Ninety patients were included in this study, 30 in each group. The duration of post-operative naso-gastric tube placement demonstrated significance between the groups (p = 0.001), being longer for patients receiving botulinum treatment. The requirement for endoscopic pyloric treatment after surgery was again poorer for those receiving botulinum (p = 0.032 and 0.003 for inpatient and outpatient endoscopy, respectively). CONCLUSION: We did not find evidence of superiority of surgical treatment or botulinum toxin of the pylorus, as prophylactic treatment for potential delayed gastric emptying after oesophagectomy, compared to no treatment at all. Based on our findings, no treatment of the pylorus yielded the most favourable outcomes.


Subject(s)
Botulinum Toxins/administration & dosage , Esophageal Neoplasms/surgery , Gastroparesis/prevention & control , Neurotoxins/administration & dosage , Pylorus/drug effects , Pylorus/surgery , Adult , Aged , Aged, 80 and over , Endoscopy, Gastrointestinal , Esophagectomy/adverse effects , Female , Gastric Emptying , Gastroparesis/etiology , Humans , Intubation, Gastrointestinal , Length of Stay , Male , Middle Aged , Postoperative Period , Retrospective Studies , Time Factors , Young Adult
13.
Updates Surg ; 70(2): 293-299, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29582358

ABSTRACT

There is no consensus on follow-up after gastric surgery for cancer, nor evidence that it improves outcomes. We investigated the impact of intensity of follow-up, comparing the regimens adopted by two centres, in Italy and in the UK. Patients who underwent surgery for gastric and junctional type-3 adenocarcinoma, between September 2009 and April 2013, at the Surgical Clinic, University of Brescia (Italy), and at the Department of Upper Gastrointestinal Surgery, University College London Hospital (UK), were identified. Patients' demographics, stage, recurrence rates, modality of detection and treatment were recorded. Overall survival and costs were compared between the two protocols. A total of 128 patients were included. Recurrence rates were similar (p = 0.349), with more than 70% diagnosed during regular follow-up appointments in both centres. At univariate and multivariate analysis, stage I and treatment of recurrence were associated with a better survival. Patients treated for recurrence at the Italian centre showed an almost significant better survival (p = 0.052). The intensive Italian surveillance protocol was associated with significant higher costs per year. Follow-up and early detection of recurrence did not affect survival in the analysed series, focused on periods in which chemotherapy was ineffective towards recurrence. However, intensive follow-up allowed a greater number of patients to receive a treatment for recurrence; this might prove useful in the next few years, when more effective chemotherapy combinations are expected to become available. The costs could be reduced by adopting a less intensive surveillance programme.


Subject(s)
Adenocarcinoma/surgery , Aftercare/methods , Gastrectomy , Neoplasm Recurrence, Local/diagnosis , Stomach Neoplasms/surgery , Adenocarcinoma/mortality , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Italy/epidemiology , Male , Middle Aged , Neoplasm Recurrence, Local/epidemiology , Retrospective Studies , Stomach Neoplasms/mortality , Survival Analysis , United Kingdom/epidemiology
14.
J Surg Oncol ; 114(6): 731-735, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27539093

ABSTRACT

Esophageal cancer has a poor prognosis, with little improvement in outcomes in recent years. Surgery maintains its pivotal role in cure, but this involves two or three compartment dissection with associated high risks. Chiefly, pulmonary complications following surgery are most common, and can be life-threatening. As a consequence, minimally invasive and robotic esophagectomy have been performed with improving efficacy and equivalent oncological outcomes. This is a review of the pertinent literature regarding these techniques. J. Surg. Oncol. 2016;114:731-735. © 2016 Wiley Periodicals, Inc.


Subject(s)
Esophageal Neoplasms/surgery , Esophagectomy/methods , Laparoscopy/methods , Robotic Surgical Procedures/methods , Thoracoscopy/methods , Humans , Treatment Outcome
15.
J Gastrointest Cancer ; 46(3): 267-71, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25952408

ABSTRACT

BACKGROUND: Despite advances in imaging techniques, peritoneal and/or metastatic disease have been identified by staging laparoscopy in up to 50 % of patients with a negative preoperative imaging. Neutrophil to lymphocyte ratio (NLR) has been recently shown as a prognostic factor in gastric and esophageal cancers. METHODS: We retrospectively reviewed the medical records of 117 patients with early gastric and lower esophagus adenocarcinoma that were referred for staging laparoscopy in the last two years in the University College Hospital, London. Complete blood count was performed preceding staging laparoscopy. The NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count; a high NLR was defined ≥3.28. We evaluated the predictive power of a high NLR for a positive staging laparoscopy. RESULTS: The median age was 66.7 years; 87 (74.4 %) were male. Forty-four percent of the tumors were located at the gastroesophageal junction, 18 % were esophageal, and 38 % were gastric. Twenty-five (21.4 %) patients were found to have peritoneal or metastatic disease on staging laparoscopy. NLR ≥3.28 was an independent predicting factor for the discovery of peritoneal and/or metastatic disease (OR 3.9, 95 % CI: 1.54-9.86, p = 0.005). The median value of NLR was significantly higher in patients for whom the laparoscopy had discovered peritoneal or metastatic disease, than in those it had not (3.3 vs. 2.2, p = 0.011). CONCLUSION: Our findings suggest that the NLR may be reliable for predicting the presence of peritoneal or metastatic involvement on staging laparoscopy, in patients with early gastric cancer or lower esophageal cancer.


Subject(s)
Adenocarcinoma/metabolism , Adenocarcinoma/surgery , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/surgery , Laparoscopy/methods , Lymphocytes/metabolism , Neutrophils/metabolism , Peritoneal Neoplasms/secondary , Stomach Neoplasms/metabolism , Stomach Neoplasms/surgery , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Esophageal Neoplasms/pathology , Female , Humans , Lymphocytes/cytology , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Neutrophils/cytology , Peritoneal Neoplasms/pathology , Retrospective Studies , Stomach Neoplasms/pathology
17.
Surg Infect (Larchmt) ; 8(4): 479-82, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17883365

ABSTRACT

BACKGROUND: Candida albicans osteo-costochondromyelitis is a rare condition. Such pathology after esophagectomy has not been reported. METHODS: Report of four cases and review of pertinent English-language literature. RESULTS: Four patients underwent esophageal surgery via a left thoraco-abdominal approach between June, 1999 and March, 2000. After complicated post-operative courses, Candida osteomyelitis of the costochondral margin presented initially as a cutaneous sinus. CONCLUSIONS: All patients responded well to surgical debridement followed by a three-month course of oral fluconazole.


Subject(s)
Candidiasis/drug therapy , Osteochondritis/microbiology , Osteomyelitis/microbiology , Surgical Wound Infection/microbiology , Antifungal Agents/therapeutic use , Candidiasis/complications , Candidiasis/etiology , Debridement , Esophagus/surgery , Fluconazole/therapeutic use , Humans , Male , Middle Aged , Osteochondritis/drug therapy , Osteomyelitis/drug therapy , Surgical Wound Infection/drug therapy , Thoracic Cavity/surgery , Thoracic Surgical Procedures/adverse effects
18.
Eur J Gastroenterol Hepatol ; 19(9): 775-82, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17700263

ABSTRACT

BACKGROUND: The vasoactive peptide endothelin-1 (ET-1) acts via two endothelin receptor subtypes, ETA (ETAR) and ETB (ETBR). ET-1 and ETAR are overexpressed in colorectal cancer tissues. In vitro, ET-1 acting via ETAR, is a mitogen for colorectal cancer cells. To identify other potential stimulatory loops, we investigated the distribution and cell-specific localization of both ETAR and ETBR in tissue sections from patients with colorectal cancer. METHODS: Frozen sections from specimens of colorectal cancer (n=9) and normal colon (n=9) were cut and subjected to either (i) autoradiography or (ii) a combination of cell type-specific immunohistochemistry, using antibodies against fibroblasts (AS02), endothelial cells (CD31) or nerve fibres (NF200) and in-vitro receptor microautoradiography, using ETAR-specific and ETBR-specific radioligands. RESULTS: ETARs were upregulated in all cell types, apart from nerve, in cancer compared with normal colon (1:1.59 normal to cancer). Specifically, ETAR binding was highest in cancer-associated blood vessels and fibroblasts and to a lesser extent in epithelial cancer cells. In contrast, ETBRs were the predominant receptors in normal colon (1:0.59 normal to cancer) and were markedly down-regulated in cancer-associated blood vessels, fibroblasts and to a lesser extent in epithelial cells. Nerve colocalization was demonstrated, but remained unchanged for all tissues. CONCLUSION: The shift in ET receptor binding observed in epithelial cancer cells and cancer-associated fibroblasts and endothelial cells may favour ET-1 signals contributing to colorectal cancer growth and neovascularization via ETAR. This may provide the basis for therapeutic use of specific ETAR antagonists as adjuvant treatment of colorectal cancer.


Subject(s)
Colorectal Neoplasms/metabolism , Receptor, Endothelin A/metabolism , Receptor, Endothelin B/metabolism , Colon/metabolism , Colorectal Neoplasms/blood supply , Endothelin-1/metabolism , Endothelium, Vascular/metabolism , Fibroblasts/metabolism , Humans , Immunoenzyme Techniques , Neoplasm Proteins/metabolism , Neovascularization, Pathologic/metabolism , Up-Regulation
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