Search PubMed⌕ Search

Biomedical subjects

P H Chapuis

Publications and source records attributed to P H Chapuis.

At least 19 recordsLinked to original sources

Assessing the evidence for an association between circumferential tumour clearance and local recurrence after resection of rectal cancer.

OBJECTIVE: Circumferential resection margin involvement (CRMI) after resection of rectal cancer is regarded as a risk factor for local recurrence. We have been able to identify only nine peer-reviewed English-language publications which focus primarily on this association, and they report widely differing rates of local recurrence. The aims of this study were to review possible reasons for this variability and to assess the evidence for the micrometrically measured threshold defining CRMI. METHOD: Methodological and statistical evaluation of relevant literature. RESULTS: Several factors which could account for this variability are discussed including the nature of the patient series, surgical technique, curative vs palliative resections, pathology technique, the definition of CRMI, adjuvant therapy, tumour stage, definition and ascertainment of local recurrence, length of follow-up and method of analysis. The objective evidence for the conventional definition of CRMI as tumour 1 mm or less from a circumferential margin is considered along with the evidence supporting a recent proposal that the margin be extended to 2 mm or less. The evidence is numerically weak in both cases and we believe that neither definition should be set in concrete at this stage. CONCLUSION: Pending further research, we recommend that routine pathology reports should record frank tumour transection, if present, or otherwise report the histological width of the margin between the tumour and the nearest circumferential line of resection in millimetres. The definition of CRMI should be simply histological evidence of tumour in a line of resection, that is, a margin of 0 mm. The definition of CRMI as a margin of <or=1 mm should not be adopted as a basis for assessing the quality of surgery.

Humans↗

Local recurrence after curative resection for rectal cancer is associated with anterior position of the tumour.

BACKGROUND: Mobilization of rectal cancer can be difficult if the tumour is located anteriorly and may result in a higher incidence of local recurrence. The aim of this study was to determine whether local recurrence and survival following curative resection of rectal cancer were associated with the position of the tumour. METHODS: Data were drawn from a comprehensive, prospective hospital registry of all resections for rectal cancer from January 1990 to December 1998, with follow-up to December 2003. RESULTS: The 5-year local recurrence rate was 15.9 (95 per cent confidence interval (c.i.) 11.0 to 22.8) per cent in 176 patients with tumours that had an anterior component compared with 5.8 (95 per cent c.i. 2.8 to 11.9) per cent in 132 patients with tumours without an anterior component (P = 0.009). This association persisted after adjustment for other factors linked to local recurrence (hazard ratio (HR) 2.4 (95 per cent c.i. 1.1 to 5.4)). Similarly, anterior position had a significant negative independent association with survival (HR 1.4 (95 per cent c.i. 1.0 to 2.00)). CONCLUSION: Anterior position is an independent negative prognostic factor for both local recurrence and survival after curative resection of rectal cancer.

Adult↗

Risk factors for tumour present in a circumferential line of resection after excision of rectal cancer.

BACKGROUND: Transected tumour in a circumferential line of resection after excision of rectal cancer carries a high likelihood of local recurrence. The aim of this study was to identify independent risk factors for transected tumour and to examine their temporal variability. METHODS: Data were drawn from a comprehensive, prospective hospital registry of all resections for rectal cancer from January 1971 to July 2004. Transected tumour was defined as tumour present histologically in a line of resection and was assessed in all specimens. RESULTS: Transection occurred in 129 of 1613 patients (8.0 (95 per cent confidence interval 6.7 to 9.4) per cent). The following variables were independently associated with transected tumour: tumour perforation, a non-restorative operation, tumour adherence, non-standardized operative technique, preoperative radiotherapy, male sex, histological involvement of an adjacent organ or tissue, high-grade tumour and venous invasion. The mean number of risk factors per patient per year and the annual percentage of patients with transection varied distinctly over the history of the database. CONCLUSION: The varying prevalence of risk factors, both within and between hospitals and patient series, should be taken into account if the rate of transection is to be regarded as an index of the quality of surgery.

Aged↗

Effect of supervised surgical training on outcomes after resection of colorectal cancer.

BACKGROUND: The process of training surgeons in technique for resection of colorectal cancer should not compromise patient care or outcomes. The aim of this study was to compare morbidity, mortality and survival rates after resection performed by trainees with those for a consultant surgeon. METHODS: Outcomes for 150 patients operated on by a single colorectal surgeon at a private hospital were compared with those of 344 patients admitted under the same surgeon and operated on by closely supervised trainee surgeons in a public teaching hospital between 1995 and 2002. RESULTS: Co-morbidity was significantly more common in patients operated on by trainees; their American Society of Anesthesiologists grades were higher and tumours were more advanced. Of 16 postoperative complications evaluated, only respiratory and cardiac problems were significantly more common in patients operated on by trainees. There was no difference in operative mortality, local recurrence or 2-year survival rate after adjustment for age and tumour stage. CONCLUSION: Outcomes after resection for colorectal cancer did not differ between the consultant and trainees in the context of a closely supervised training programme.

Aged↗

What factors influence survival in patients with unresected synchronous liver metastases after resection of colorectal cancer?

OBJECTIVE: The aim of this study was to determine whether the survival of patients with untreated synchronous liver metastases after resection of a colorectal cancer was associated with any features of the primary tumour. METHODS: Information for 398 consecutive patients with unresected liver metastases in the period 1971-2001 was examined by multivariate survival analysis. RESULTS: Of 19 clinical and pathological variables considered, survival was independently associated only with residual tumour in a line of resection (hazard ratio (HR) 1.95), venous invasion (HR 1.87), right colonic tumour (HR 1.68), lymph node metastasis (HR 1.54), and extra-hepatic metastasis (HR 1.16); 8.3% of patients had none of these adverse features. Their 2-year overall survival rate was 39.2%, compared with only 16.5% (P < 0.001) in those with one or more adverse features. CONCLUSIONS: These findings may assist in selecting patients most likely to benefit from treatment of hepatic metastases and in counselling patients and their relatives.

Aged↗

Low level microsatellite instability may be associated with reduced cancer specific survival in sporadic stage C colorectal carcinoma.

BACKGROUND: Colorectal cancers (CRCs) may be categorised according to the degree of microsatellite instability (MSI) exhibited, as MSI-high (MSI-H), MSI-low (MSI-L), or microsatellite stable (MSS). MSI-H status confers a survival advantage to patients with sporadic CRC. AIMS: To determine if low levels of MSI are related to the clinicopathological features and prognosis of sporadic stage C CRC. PATIENTS: A total of 255 patients who underwent resection for sporadic stage C CRC were studied. No patient received chemotherapy. Minimum follow up was five years. METHODS: DNA extracted from archival malignant and non-malignant tissue was amplified by polymerase chain reaction using a panel of 11 microsatellites. MSI-H was defined as instability at > or =40% of markers, MSS as no instability, and MSI-L as instability at >0% but <40% of markers. Patients with MSI-H CRC were excluded from analysis as they have previously been shown to have better survival. RESULTS: Thirty three MSI-L and 176 MSS CRCs were identified. There was no difference in biological characteristics or overall survival of MSI-L compared with MSS CRC but MSI-L was associated with poorer cancer specific survival (hazard ratio 2.0 (95% confidence interval 1.1-3.6)). CONCLUSIONS: Sporadic MSI-L and MSS CRCs have comparable clinicopathological features. Further studies are required to assess the impact of MSI-L on prognosis.

Adult↗

Adverse histopathological findings as a guide to patient management after curative resection of node-positive colonic cancer.

BACKGROUND: The aim of this study was to identify patient and tumour characteristics that might assist in developing an improved approach to patient selection for chemotherapy after resection of clinicopathological stage C colonic cancer. METHODS: Clinical, pathological and follow-up data have been collected prospectively for all patients undergoing resection for colorectal cancer at Concord Hospital since 1971. From an initial 2980 patients, after exclusions 378 remained who had a potentially curative operation for colonic cancer with nodal metastases and did not receive adjuvant chemotherapy. Associations between several pathological features and survival were examined by proportional hazards regression. RESULTS: In a multivariate model, both overall and colonic cancer-specific survival rates were negatively associated with serosal surface involvement, apical node metastasis, high histological grade and venous invasion. The survival of patients with stage C disease who had none of these adverse features was not significantly different from that of patients with stage B lesions. However, survival diminished significantly when one or more of the adverse features were present. CONCLUSION: Patients with a stage C tumour but with none of the identified adverse features experience relatively good survival and are unlikely to benefit from adjuvant chemotherapy. In this series such patients accounted for 40.5 per cent of patients with stage C disease.

Aged↗

Anastomotic leakage after curative anterior resection results in a higher prevalence of local recurrence.

BACKGROUND: The aim of this study was to determine whether leakage from a colorectal anastomosis following potentially curative anterior resection for rectal cancer is an independent risk factor for local recurrence. METHODS: The study included all patients who had a potentially curative anterior resection with anastomosis for adenocarcinoma of the rectum between 1971 and 1991 at Concord Hospital. The data were collected prospectively, with complete follow-up for at least 5 years. The Kaplan-Meier method was used to compare time to recurrence between strata of categorical variables. Proportional hazards regression was used in multivariate modelling. RESULTS: There were 403 patients in the study. After adjustment for lymph node metastases, the distal resection margin of resection, non-total anatomical dissection of the rectum and the level of anastomosis, multivariate analysis identified a significant association between anastomotic leakage and local recurrence (hazard ratio 3.8, 95 per cent confidence interval 1.8 to 7.9). CONCLUSION: Leakage following a colorectal anastomosis after potentially curative resection for adenocarcinoma of the rectum is an independent predictor of local recurrence.

Adenocarcinoma↗

Surgical technique and survival in patients having a curative resection for colon cancer.

PURPOSE: This study was performed to determine whether the adoption of a standardized technique for resection of colon cancer, based on mobilization along anatomic planes, resulted in improved survival after adjustment for other known prognostic factors. METHODS: Patients undergoing a potentially curative, elective colonic resection at Concord Hospital from 1971 to 1995 were included. None received adjuvant therapy. Data were recorded prospectively. Overall survival and colon-cancer-specific survival were examined by the Kaplan-Meier method and proportional-hazards regression in relation to patient and tumor characteristics and the introduction of a standardized surgical technique in 1980. RESULTS: Overall five-year survival rose from 48.1 percent before 1980 to 63.7 percent after 1980 (P < 0.0001); cancer-specific survival rose from 66.4 percent to 76.6 percent (P = 0.002). Factors that did not change significantly before and after 1980 were patient age and gender, tumor site, stage, grade, serosal surface involvement, and apical node metastases. The proportion of tumors > or =5 cm in diameter decreased after 1980 (61.9 to 49.2 percent, P = 0.001) but survival was unrelated to size. Venous invasion rose after 1980 (9 to 15.8 percent, P = 0.014). Multiple regression with adjustment for age, stage, grade, venous invasion, serosal surface involvement, and apical node metastases showed significantly shorter overall survival before the introduction of the standardized technique (hazard ratio, 1.5; 95 percent confidence interval, 1.2-1.8) and significantly shorter colon-cancer-specific survival (hazard ratio, 1.7; 95 percent confidence interval, 1.3-2.2). The proportion of patients having a noncurative operation because of residual tumor in a line of resection (excluded from the survival analyses) fell from 10.6 percent (confidence interval, 7-15.3 percent) before 1980 to 3.2 percent (confidence interval, 2-4.9 percent) after 1980. CONCLUSION: As in rectal cancer surgery, mobilization of the colon along anatomic planes is an important principle that influences outcome and needs to be emphasized.

Aged↗

Combined endoscopic laser and radiotherapy palliation of advanced rectal cancer.

BACKGROUND: In the palliative treatment of patients with advanced, inoperable rectal cancer, combined endoscopic laser and radiotherapy have been claimed to be more effective than laser therapy alone. The number of laser treatments, laser energy used, relapse rate, treatment of relapse, morbidity and survival in consecutive patients who were treated either by laser therapy alone or laser plus radiotherapy was compared. METHODS: Prospective data were analysed with regard to number of treatments, laser energy used, relapse rate, morbidity and survival for 56 consecutive patients. RESULTS: The crude relapse rate was significantly higher in the laser only group than in the laser plus radiotherapy group (58 and 15%, respectively; P = 0.002). There was no difference between the groups in the median total number of laser treatments or the mean total laser energy used. In patients experiencing a relapse, there was no difference in the median number of relapses, the number of laser treatments post-relapse or the total energy used post-relapse. Survival did not differ between the groups and there were no treatment-related deaths. CONCLUSIONS: These findings demonstrate a clear reduction in relapse after using combined laser and radiotherapy to palliate patients with advanced rectal cancer with no appreciable additional morbidity and have encouraged continuing use of this treatment.

Aged↗

Methodology and reporting in studies of local recurrence after curative excision of the rectum for cancer.

BACKGROUND: Widely varying rates have been reported in the extensive literature published in the English language on local recurrence after curative excision of rectal carcinoma. These variations may be attributable to differences in the case mix of pathological factors influencing recurrence, differences in surgical technique or expertise, differences in the administration of adjuvant therapy and various combinations of these. They may also arise from methodological differences among studies. METHODS: This paper reviews the adequacy of methodology and reporting in 21 recent studies of local recurrence after curative resection of rectal cancer. RESULTS: Many flaws in reporting and apparent inadequacies in methodology were identified. On an index of 26 criteria examined, eight studies scored no more than 8 and only three studies scored more than 11. CONCLUSION: To date, the value of reports of local recurrence rates following curative excision of rectal cancer has been limited by inadequacies in documentation and methodology. Suggestions are made for preferred procedures to be followed in the reporting of future studies.

Clinical Trials as Topic↗

Prognostic significance of extensive microsatellite instability in sporadic clinicopathological stage C colorectal cancer.

BACKGROUND: Colorectal cancers exhibiting microsatellite instability (MSI) appear to have unique biological behaviour. This study analyses the association between extensive MSI (MSI-H), clinicopathological features and survival in an unselected group of patients with sporadic Australian Clinico-Pathological Stage (ACPS) C (tumour node metastasis stage III) colorectal cancer. METHODS: Some 255 patients who underwent resection for sporadic ACPS C colorectal cancer between 1986 and 1992 were studied. No patient had received chemotherapy. Minimum follow-up for all patients was 5 years. Archival normal and tumour DNA was extracted and amplified by polymerase chain reaction using a radioactive labelling technique. MSI-H was defined as instability in 40 per cent or more of seven markers. RESULTS: Twenty-one patients showed MSI-H. No association was found between MSI and age or sex. Tumours exhibiting MSI-H were more commonly right sided (P<0.00001), larger (P = 0.002) and more likely to be high grade (P = 0.049). After adjustment for age, sex and other pathological variables, patients whose cancers exhibited MSI-H had improved survival (P = 0.015). CONCLUSION: Recognition of MSI-H in sporadic ACPS C tumours identifies a subset of cancers with improved prognosis. Such stratification should be considered in trials of adjuvant therapy and may be relevant to therapeutic decision making.

Adult↗

Immobiline-based two-dimensional gel electrophoresis: an optimised protocol for resolution of human colonic mucosal proteins.

An optimised protocol for the production of two-dimensional protein patterns of human colonic mucosal cells using immobilised pH gradients in the first dimension is presented. We tested a wide variety of solubilising agents and electrophoretic parameters, separately and in combination. Protein solubilisation was found to be best using a lysis solution containing 9 M urea, 2% Triton X-100, 2% 2-mercaptoethanol, 0.8% Pharmalyte pH 3-10 and 8 mM phenylmethylsulfonyl fluoride (PMSF). Horizontal streaking of basic proteins in the first dimension was virtually eliminated by a combination of washing Immobiline strips in 100 mM asorbic acid, pH 4.5, for 24 h before use and isoelectric focusing samples at 40 degrees C. The presence of 2% glycerol in the first dimension resulted in tighter resolution throughout the entire pH range. The use of these conditions may prove to have broad applicability to the generation of optimally resolved Immobiline-based two-dimensional protein patterns of many other tissues.

Acrylamides↗