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Biomedical subjects

Philip Quirke

Publications and source records attributed to Philip Quirke.

5 recordsLinked to original sources

Low rectal cancer: a call for a change of approach in abdominoperineal resection.

PURPOSE: Despite the major improvements that have been made due to total mesorectal excision (TME), low rectal cancer still remains a challenge. METHODS: By investigating a prospective randomized rectal cancer trial in which surgeons had undergone training in TME the factors responsible for the poor outcome were determined and a new method for assessing the quality of surgery was tested. RESULTS: Survival differed greatly between abdominoperineal resection (APR) and anterior resection (AR; 38.5% v 57.6%, P = .008). Low rectal carcinomas have a higher frequency of circumferential margin involvement (26.5% v 12.6%, P < .001). More positive margins were present in the patients operated with APR (30.4%) compared to AR (10.7%, P = .002). Furthermore, more perforations were present in these specimens (13.7% v 2.5%, P < .001). The plane of resection lies within the sphincteric muscle, the submucosa or lumen in more than 1/3 of the APR cases, and in the remainder lay on the sphincteric muscles. CONCLUSION: We systematically described and investigated the pathologic properties of low rectal cancer in general, and APR in particular, in a prospective randomized trial including surgeons who had been trained in TME. The poor prognosis of the patients with an APR is ascribed to the resection plane of the operation leading to a high frequency of margin involvement by tumor and perforation with this current surgical technique. The clinical results of this operation could be greatly improved by adopting different surgical techniques and possibly greater use of radiochemotherapy.

Anal Canal↗

TmaDB: a repository for tissue microarray data.

BACKGROUND: Tissue microarray (TMA) technology has been developed to facilitate large, genome-scale molecular pathology studies. This technique provides a high-throughput method for analyzing a large cohort of clinical specimens in a single experiment thereby permitting the parallel analysis of molecular alterations (at the DNA, RNA, or protein level) in thousands of tissue specimens. As a vast quantity of data can be generated in a single TMA experiment a systematic approach is required for the storage and analysis of such data. DESCRIPTION: To analyse TMA output a relational database (known as TmaDB) has been developed to collate all aspects of information relating to TMAs. These data include the TMA construction protocol, experimental protocol and results from the various immunocytological and histochemical staining experiments including the scanned images for each of the TMA cores. Furthermore the database contains pathological information associated with each of the specimens on the TMA slide, the location of the various TMAs and the individual specimen blocks (from which cores were taken) in the laboratory and their current status i.e. if they can be sectioned into further slides or if they are exhausted. TmaDB has been designed to incorporate and extend many of the published common data elements and the XML format for TMA experiments and is therefore compatible with the TMA data exchange specifications developed by the Association for Pathology Informatics community. Finally the design of the database is made flexible such that TMA experiments from several types of cancer can be stored in a single database, which incorporates the national minimum data set required for pathology reports supported by the Royal College of Pathologists (UK). CONCLUSION: TmaDB will provide a comprehensive repository for TMA data such that a large number of results from the numerous immunostaining experiments can be efficiently compared for each of the TMA cores. This will allow a systematic, large-scale comparison of tumour samples to facilitate the identification of gene products of clinical importance such as therapeutic or prognostic markers. In addition this work will contribute to the establishment of a standard for reporting TMA data analogous to MIAME in the description of microarray data.

Data Interpretation, Statistical↗

The modern abdominoperineal excision: the next challenge after total mesorectal excision.

OBJECTIVES: Examine the cause of local recurrence (LR) and patient survival (S) following abdominoperineal resection (APR) and anterior resection (AR) for rectal carcinoma and the effect of introduction of total mesorectal excision (TME) on APR. METHODS: A total of 608 patients underwent surgery for rectal cancer in Leeds from 1986 to 1997. CRM status and follow-up data of local recurrence and patient survival were available for 561 patients, of whom 190 underwent APR (32.4%) and 371 AR (63.3%). Also, a retrospective study of pathologic images of 93 specimens of rectal carcinoma. RESULTS: Patients undergoing APR had a higher LR and lower survival (LR, 22.3% versus 13.5%, P = 0.002; S, 52.3% versus 65.8%, P = 0.003) than AR. LR free rates were lower in the APR group and cancer specific survival was lowered (LR, 66% versus 77%, log rank P = 0.03; S, 48% versus 59%, log rank P = 0.02). Morphometry: total area of surgically removed tissue outside the muscularis propria was smaller in APR specimens (n = 27) than AR specimens (n = 66) (P < 0.0001). Linear dimensions of transverse slices of tissue containing tumor, median posterior, and lateral measurements were smaller (P < 0.05) in the APR than the AR group. APR specimens with histologically positive CRM (n = 11) had a smaller area of tissue outside the muscularis propria (P = 0.04) compared with the CRM-negative APR specimens (n = 16). Incidence of CRM involvement in the APR group (41%) was higher than in the AR group (12%) (P = 0.006) in the 1997 to 2000 cohort. Similar results (36% and 22%) were found in the 1986 to 1997 cohort (P = 0.002). CONCLUSIONS: Patients treated by APR have a higher rate of CRM involvement, a higher LR, and poorer prognosis than AR. The frequency of CRM involvement for APR has not diminished with TME. CRM involvement in the APR specimens is related to the removal of less tissue at the level of the tumor in an APR. Where possible, a more radical operation should be considered for all low rectal cancer tumors.

Adenocarcinoma↗

Rates of circumferential resection margin involvement vary between surgeons and predict outcomes in rectal cancer surgery.

OBJECTIVE: To analyze the potential variability in rates of circumferential resection margin (CRM) involvement between different surgeons and time periods and to determine the suitability of using CRM status as an immediate predictor of outcome after rectal cancer surgery. SUMMARY BACKGROUND DATA: After disease stage has been taken into account, survival in rectal cancer has been shown to be very variable between surgeons and institutions. One of the major factors influencing survival is local recurrence, and this in turn is strongly related to inadequate tumor excision, particularly at the CRM. METHODS: In a study involving 608 patients who underwent surgery for rectal cancer in Leeds during the 12-year period 1986 to 1997, the authors examined the role of CRM status as an immediate predictor of likely outcome, paying particular attention to its relationships with different surgeons and time periods. RESULTS: Of 586 patients on whom full clinical follow-up was obtained, 165 (28.2%) had CRM involvement by carcinoma on pathologic examination. Up to the end of 1998, 105 (17.9%) patients had developed local recurrence. A significantly higher proportion (38.2%) of CRM-positive patients developed local recurrence than CRM-negative ones (10.0%). Kaplan-Meier survival analysis showed significant improvements in survival for CRM-negative patients over CRM-positive patients. Survival analysis in relation to two gastrointestinal surgeons and a group of other surgeons showed survival improvements that paralleled a reduction in the rates of CRM involvement for the two gastrointestinal surgeons during the period of the study. No improvement in survival or reduction in rates of CRM involvement was seen in the group of other surgeons. CONCLUSIONS: These results show that CRM status may be used as an immediate predictor of survival after rectal cancer surgery and serves as a useful indicator of the quality of surgery. The frequency of CRM involvement can be used both for overall surgical audit and for monitoring the value of training programs in improving rectal surgery by individual surgeons. Its use in the current MRC CR07 study is valid and the best indicator of a requirement for further local therapy.

Adenocarcinoma↗

Short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer (MRC CLASICC trial): multicentre, randomised controlled trial.

BACKGROUND: Laparoscopic-assisted surgery for colorectal cancer has been widely adopted without data from large-scale randomised trials to support its use. We compared short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer to predict long-term outcomes. METHODS: Between July, 1996, and July, 2002, we undertook a multicentre, randomised clinical trial in 794 patients with colorectal cancer from 27 UK centres. Patients were allocated to receive laparoscopic-assisted (n=526) or open surgery (n=268). Primary short-term endpoints were positivity rates of circumferential and longitudinal resection margins, proportion of Dukes' C2 tumours, and in-hospital mortality. Analysis was by intention to treat. This trial has been assigned the International Standard Randomised Controlled Trial Number ISRCTN74883561. FINDINGS: Six patients (two [open], four [laparoscopic]) had no surgery, and 23 had missing surgical data (nine, 14). 253 and 484 patients actually received open and laparoscopic-assisted treatment, respectively. 143 (29%) patients underwent conversion from laparoscopic to open surgery. Proportion of Dukes' C2 tumours did not differ between treatments (18 [7%] patients, open vs 34 [6%], laparoscopic; difference -0.3%, 95% CI -3.9 to 3.4%, p=0.89), and neither did in-hospital mortality (13 [5%] vs 21 [4%]; -0.9%, -3.9 to 2.2%, p=0.57). Apart from patients undergoing laparoscopic anterior resection for rectal cancer, rates of positive resection margins were similar between treatment groups. Patients with converted treatment had raised complication rates. INTERPRETATION: Laparoscopic-assisted surgery for cancer of the colon is as effective as open surgery in the short term and is likely to produce similar long-term outcomes. However, impaired short-term outcomes after laparoscopic-assisted anterior resection for cancer of the rectum do not yet justify its routine use.

Aged↗