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P J Guillou

Publications and source records attributed to P J Guillou.

At least 19 recordsLinked to original sources
PubMed2006

Short-term costs of conventional vs laparoscopic assisted surgery in patients with colorectal cancer (MRC CLASICC trial).

The short-term clinical results of the CLASICC trial indicated that clinical outcomes were similar between laparoscopic and open approaches. This study presents the short-term (3 month) cost analysis undertaken on a subset of patients entered into the CLASICC trial (682 of 794 patients). As expected the costs associated with the operation were higher in the 452 patients randomised to laparoscopic surgery (lap) compared with the 230 randomised to open procedure (open), Pounds 1703 vs Pounds 1386. This was partially offset by the other hospital (nontheatre) costs, which were lower in the lap group (Pounds 2930 vs Pounds 3176). The average cost to individuals for reoperations was higher in the lap group (Pounds 762 vs Pounds 553). Overall costs were slightly higher in the lap group (Pounds 6899 vs Pounds 6631), with mean difference of Pounds 268 (95%CI -689 to 1457). Sensitivity analysis made little difference to these results. The cost of rectal surgery was higher than for colon, for lap (Pounds 8259 vs Pounds 5586) and open procedures (Pounds 7820 vs Pounds 5503). The short-term cost analysis for the CLASICC trial indicates that the costs of either laparoscopic or open procedure were similar, lap surgery costing marginally more on average than open surgery.

Colectomy↗
PubMed2006

Redefining the R1 resection in pancreatic cancer.

BACKGROUND: Resection margin (RM) status in pancreatic head adenocarcinoma is assessed histologically, but pathological examination is not standardized. The aim of this study was to assess the influence of standardized pathological examination on the reporting of RM status. METHODS: A standardized protocol (SP) for pancreaticoduodenectomy specimen examination, involving multicolour margin staining, axial slicing and extensive tissue sampling, was developed. R1 resection was defined as tumour within 1 mm of the RM. A prospective series reported according to this protocol (SP series, n = 54) was compared with a historical matched series in which a non-standardized protocol was used (NSP series, n = 48). RESULTS: Implementation of the SP resulted in a higher R1 rate overall, and for pancreatic (22 of 26 85 per cent) compared with ampullary (four of 15) and bile duct (six of 13) cancer. Sampling of the circumferential RM was more extensive in the SP series and correlated with RM status. RM involvement was often multifocal (14 of 32), affecting the posterior RM most frequently (21 of 32). Survival correlated with RM status for the entire SP series (P < 0.001), but not for the NSP series. There was a trend towards better median and actuarial 5-year survival after R0 resection in the SP pancreatic cancer subgroup. CONCLUSION: Standardized examination influences the reporting of RM status.

Adenocarcinoma↗
PubMed2006

[Ocular melanoma: immunohistochemical evaluation of the potentially predictive markers of prognosis. Preliminary results].

PURPOSE: To study the characteristics of certain biological parameters, many of which have been recently discovered, to assess their possible contribution to the prognosis of ocular melanoma. MATERIAL: and methods: 25 patients with ocular and orbital melanoma treated at the Reims Regional Hospital since 1993 were included in the retrospective study. The surgical specimens were put in formalin 10%, then in paraffin. Five proteins were analyzed retrospectively: topoisomerase I, topoisomerase IIalpha, ICBP90, Ki67, and P53 on 200 cells per case. RESULTS: Of the 25 tumors from 14 men and 11 women, 15 were iris and ciliary body melanomas and ten choroidal melanomas. Histopathologic analysis showed 12 spindle-cell-type melanomas, seven epithelioid-cell-type melanomas and six mixed-cell-type melanomas. The immunohistochemical study found a significant difference in distribution between the cellular types for the topoisomerase IIalpha and Ki67 antibodies. Eight patients had metastasis, six of whom died. The metastasis came from three mixed-cell-type melanomas, three epithelioid-cell-type melanomas, and two spindle-cell-type melanomas. On the other hand, six cases of sclera infiltration were discovered among these eight patients. CONCLUSION: Several prognostic factors seem to be involved in the progression of melanoma: sclera infiltration seems to be essential in our study. Its rate seems to increase with the tumor size and in epithelioid-cell-type melanomas. The correlation between the different immunomarkers and the appearance of metastasis has not yet been verified.

Adult↗
PubMed2005

Successful outcome following resection of a pancreatic liposarcoma with solitary metastasis.

Liposarcomas are rare soft tissue tumors, commonly affecting the lower limbs and less commonly the retroperitoneum. Although other organs can be affected, the pancreas is one of the rarest, and metastasis at presentation has never been reported. We describe the case of a 76-year-old gentleman presenting with abdominal pain and an abdominal mass. Imaging confirmed a primary tumor in the body and tail of the pancreas, with a metastatic deposit in the mesentery adjacent to the second part of the duodenum. Biopsy confirmed a liposarcoma, and subsequently a complete surgical excision was achieved. He then received adjuvant radiotherapy and has remained disease free for the next 26 mo.

Aged↗
PubMed2005

Bladder and sexual function following resection for rectal cancer in a randomized clinical trial of laparoscopic versus open technique.

BACKGROUND: Bladder and sexual dysfunction are recognized complications of mesorectal resection. Their incidence following laparoscopic surgery is unknown. METHODS: Bladder and sexual function were assessed in patients who had undergone laparoscopic rectal, open rectal or laparoscopic colonic resection as part of the UK Medical Research Council Conventional versus Laparoscopic-Assisted Surgery In Colorectal Cancer (CLASICC) trial, using the International Prostatic Symptom Score, the International Index of Erectile Function and the Female Sexual Function Index. Sexual and bladder function data from the European Organization for Research and Treatment of Cancer QLQ-CR38 collected in the CLASICC trial were used for comparison. RESULTS: Two hundred and forty-seven (71.2 per cent) of 347 patients completed questionnaires. Bladder function was similar after laparoscopic and open rectal operations for rectal cancer. Overall sexual function and erectile function tended to be worse in men after laparoscopic rectal surgery than after open rectal surgery (overall function: difference - 11.18 (95 per cent confidence interval (c.i.) -22.99 to 0.63), P = 0.063; erectile function: difference -5.84 (95 per cent c.i. -10.94 to -0.74), P = 0.068). Total mesorectal excision (TME) was more commonly performed in the laparoscopic rectal group than in the open rectal group. TME (odds ratio (OR) 6.38, P = 0.054) and conversion to open operation (OR 2.86, P = 0.041) were independent predictors of postoperative male sexual dysfunction. No differences were detected in female sexual function. CONCLUSION: Laparoscopic rectal resection did not adversely affect bladder function, but there was a trend towards worse male sexual function. This may be explained by the higher rate of TME in the laparoscopic rectal resection group.

Aged↗
PubMed2004

Laparoscopic resection of colon Cancer: consensus of the European Association of Endoscopic Surgery (EAES).

BACKGROUND: The European Association of Endoscopic Surgery (EAES) initiated a consensus development conference on the laparoscopic resection of colon cancer during the annual congress in Lisbon, Portugal, in June 2002. METHODS: A systematic review of the current literature was combined with the opinions, of experts in the field of colon cancer surgery to formulate evidence-based statements and recommendations on the laparoscopic resection of colon cancer. RESULTS: Advanced age, obesity, and previous abdominal operations are not considered absolute contraindications for laparoscopic colon cancer surgery. The most common cause for conversion is the presence of bulky or invasive tumors. Laparoscopic operation takes longer to perform than the open counterpart, but the outcome is similar in terms of specimen size and pathological examination. Immediate postoperative morbidity and mortality are comparable for laparoscopic and open colonic cancer surgery. The laparoscopically operated patients had less postoperative pain, better-preserved pulmonary function, earlier restoration of gastrointestinal function, and an earlier discharge from the hospital. The postoperative stress response is lower after laparoscopic colectomy. The incidence of port site metastases is <1%. Survival after laparoscopic resection of colon cancer appears to be at least equal to survival after open resection. The costs of laparoscopic surgery for colon cancer are higher than those for open surgery. CONCLUSION: Laparoscopic resection of colon cancer is a safe and feasible procedure that improves short-term outcome. Results regarding the long-term survival of patients enrolled in large multicenter trials will determine its role in general surgery.

Colectomy↗
PubMed2004

Tumour-induced apoptosis in human mesothelial cells: a mechanism of peritoneal invasion by Fas Ligand/Fas interaction.

Gastrointestinal carcinomas frequently disseminate within the abdominal cavity to form secondary peritoneal metastases. Invasion of the peritoneal mesothelium is fundamental to this process, yet the underlying invasive mechanisms remain unclear. Preliminary in vitro work suggested that tumour cells can induce mesothelial apoptosis, representing a novel mechanism of peritoneal invasion. We examined the role of tumour cell-induced mesothelial apoptosis and explored the role of the death ligand/receptor system, Fas Ligand/Fas, as mediators of the apoptotic process. Cultured human mesothelial cells were used to establish in vitro co-culture models with the SW480 colonic cancer cell line. Tumour-induced mesothelial apoptosis was confirmed by phase-contrast microscopy and apoptotic detection assays. Human mesothelial cells and SW480 tumour cells constitutively expressed Fas and Fas Ligand mRNA and protein as determined by RT-PCR and confocal fluorescent microscopy. Stimulation of human mesothelial cells with anti-Fas monoclonal antibody or crosslinked soluble Fas Ligand-induced apoptosis, confirming the functional status of the Fas receptor. Pretreatment of SW480 cells with a blocking recombinant anti-Fas Ligand monoclonal antibody significantly reduced mesothelial apoptosis, indicating that tumour-induced mesothelial apoptosis may, in part, be mediated via a Fas-dependent mechanism. This represents a novel mechanism of mesothelial invasion and offers several new targets for therapeutic intervention.

Apoptosis↗
PubMed2004

Interleukin 13 and inflammatory markers in human sepsis.

BACKGROUND: Interleukin (IL) 13 is an anti-inflammatory cytokine that reduces inflammatory cytokine production, and enhances monocyte survival and MHC class II and CD23 expression. The only report of IL-13 in human sepsis noted no increase in IL-13 concentration, in contrast to animal data. This study further examined the expression of IL-13 in relation to human sepsis. METHODS: In a prospective observational study of 31 patients (24 men) with sepsis or septic shock, high-sensitivity enzyme-linked immunoabsorbent assay (ELISA) was used to quantify levels of tumour necrosis factor (TNF) alpha on admission, and on days 1, 3, 5 and 7 thereafter. IL-13 and IL-2 were assayed by standard ELISA, and HLA-DR on CD14-positive monocytes was measured by flow cytometry. RESULTS: Twenty-three patients developed septic shock. Monocyte HLA-DR levels showed greater depression and a slower recovery in shocked than non-shocked patients. The serum IL-13 concentration was significantly higher in the shocked group from admission to day 3, but subsequently decreased to levels similar to those in the non-shocked group. IL-13 concentrations were higher in non-survivors. The TNF-alpha concentration was higher in those with septic shock than in those without. The TNF-alpha level correlated with IL-13 concentration (r(S) = 0.61, P = 0.002). The IL-13/TNF-alpha ratio was greater in patients with shock than those with sepsis only (P = 0.017). IL-2 was undetectable. CONCLUSION: In human sepsis and septic shock, IL-13 correlated with TNF-alpha expression, but its effect on HLA-DR class II molecules remains unclear.

Adult↗
PubMed2002

Expression of survivin, a novel inhibitor of apoptosis and cell cycle regulatory protein, in pancreatic adenocarcinoma.

Survivin is unique for its expression in human malignancies but not in normal adult cells. It has been implicated in sensitisation to chemotherapy and as a prognostic marker in several common cancers. Immunohistochemistry for Survivin, P53 and BCL-2 expression as well as cell proliferative index (Ki-67) and apoptosis index (TUNEL) was conducted on 52 pancreatic and 12 ampullary adenocarcinomas. Survivin was detected in the cytoplasm of carcinoma cells in 46 (88%) of pancreatic tumours. P53 and BCL-2 were detected in 54% and 12% of pancreatic tumours, respectively. Proliferative index was 26.2+/-10.5% and apoptosis index was 1.38+/-0.69%. Prevalence of Survivin expression was significantly higher in P53-positive than in P53-negative cases (P=0.05) but was not associated with BCL-2 expression. Incrementally higher weighted scores of Survivin expression were associated with increased proliferative index (P=0.001). Furthermore, there was linear correlation between increased proliferative index and higher apoptosis index (P<0.001). Surprisingly, higher scores of Survivin expression were associated with increased apoptosis index (P=0.007). Survival characteristics were not influenced by Survivin, P53 or BCL-2 expression, apoptosis index or proliferative index. Ampullary carcinoma showed Survivin expression in 83% of cases. However, unlike pancreatic carcinoma, there was no correlation between Survivin and P53 expression or proliferative index. In conclusion, Survivin is expressed in the majority of pancreatic adenocarcinomas and correlates with both cellular proliferation and apoptosis. Molecular manipulation of Survivin expression may enhance chemotherapy and radiation therapy for pancreatic cancer.

Adenocarcinoma↗
PubMed2002

Randomized clinical trial of Ligasure versus conventional diathermy for day-case haemorrhoidectomy.

BACKGROUND: Haemorrhoidectomy is frequently associated with postoperative pain and prolonged hospital stay. A new technique of haemorrhoidectomy using the Ligasure device suited to day-case surgery is described. This technique was compared with conventional open diathermy haemorrhoidectomy. METHODS: Forty patients with grade III or IV haemorrhoids were randomized to Ligasure (group 1) or conventional diathermy (group 2) haemorrhoidectomy. Operative details were recorded and patients recorded daily pain scores on a linear analogue scale. Follow-up was at 1, 3, 6 and 12 weeks to evaluate complications, return to normal activity, ongoing symptoms and patient satisfaction. RESULTS: Reduced intraoperative blood loss (median (range) 0 (0-5) ml versus 20 (12-22) ml; P < 0.001) and a shorter operating time (10 (8-11) versus 20 (18-25) min; P < 0.001) was observed in group 1 compared with group 2. More patients in group 1 were discharged on the day of operation (18 of 20 versus 11 of 20; P < 0.05) and there was a trend towards lower postoperative pain scores on day 1 (group 1 median 5 (95 per cent confidence interval (c.i.) 2.6 to 6.8) versus group 2 7 (95 per cent c.i. 4.2 to 7.7); P = 0.36). There was no difference between the two groups in the degree of patient satisfaction or number of postoperative complications. CONCLUSION: Ligasure diathermy may be used safely in the treatment of patients with grade III or IV haemorrhoids. It reduces intraoperative blood loss and operating time, and facilitates same-day discharge.

Adult↗
PubMed2002

Extracellular matrix proteins and chemoradiotherapy: alpha5beta1 integrin as a predictive marker in rectal cancer.

AIMS: To investigate the effects of extracellular matrix (ECM) protein expression on the rates of apoptosis and proliferation in rectal cancers and subsequent response to chemoradiotherapy (CRT). METHODS: The expression of fibronectin, collagen IV, laminin and the fibronectin receptor (FnR, alpha5beta1 integrin) were analysed in 32 pre-treatment rectal cancer biopsies by immunohistochemistry. ECM expression was correlated with tumour mitotic index (MI), apoptotic index (AI) and histopathological response to CRT. RESULTS: 18/32 cancers showed a poor response and 14/32 a good response (5/14 with complete pathological response) to CRT. Moderate to strong staining was seen in 22/32 cancers for fibronectin, 5/32 for collagen IV and 18/32 for laminin. Tumour FnR was related to stromal fibronectin content, and was significantly associated with CRT response; good responders having higher FnR expression compared to poor responders. No association was found between FnR expression and either MI or AI in pre-treatment biopsies, nor between MI or AI and CRT response. CONCLUSIONS: Tumour FnR expression is independent of MI and AI, and may serve as a useful marker for CRT response in rectal cancer.

Apoptosis↗
PubMed2002

Pathological scarring: strategic interventions.

Aberrant cutaneous scar formation is a substantial cause of postoperative morbidity. There is at present no clear consensus on the best way to prevent or treat such scarring, although recently there has been considerable progress in developing an understanding of the mechanisms of tissue repair and scarring. We carried out a literature review using Medline to establish the current understanding of the key events occurring during tissue repair and to identify potential causes of scarring. We now review the key events during tissue repair and the pathogenesis of fibroproliferative disease. Tissue repair is achieved through a multistranded, elegantly coordinated process within which the balance between synthesis and breakdown of matrix is upset during fibrotic disease. Scars form because the signals directing tissue repair are not correctly terminated, and while the initiation and propagation of repair is well understood the signals that direct its cessation have yet to be elucidated.

Cicatrix↗
PubMed2001

Immunohistochemical detection of the anti-apoptosis protein, survivin, predicts survival after curative resection of stage II colorectal carcinomas.

BACKGROUND: This study examined the role of Survivin protein, a novel inhibitor of apoptosis, in determining prognosis after curative resection of stage II colorectal carcinomas. METHODS: Expression of Survivin, P53, and BCL-2 was evaluated immunohistochemically in stage II colorectal carcinomas from 49 patients who were followed for up to 9 years after operation. The Cox proportional hazards regression model was used to examine the predictive value of several covariates. RESULTS: The patients comprised 33 men and 16 women with a median age of 71 years. There were 32 colonic and 17 rectal cancers comprising 40 T3 and nine T4 primary tumors. Survivin was expressed in 30 (61.2%), P53 in 30 (61.2%), and BCL-2 in 21 (42.9%) tumors. Expression of Survivin was independent of P53 or BCL-2 expression and histopathological characteristics of the tumor. The 5-year survival rate of patients with Survivin-positive tumors was significantly lower than that of patients with Survivin-negative tumors (52.5% vs. 94.1%, respectively; P = .01). On multivariate analysis, expression of Survivin (Hazard Ratio [HR] = 9; P = .03), and rectal origin of cancer (HR = 3; P = .05) were the only factors which independently predicted an increased risk of death from recurrent cancer. CONCLUSION: Survivin expression within the tumor can identify patients with stage II colorectal carcinoma who are at increased risk of death from recurrent disease and might particularly benefit from adjuvant therapy.

Aged↗
PubMed2001

Non-operative management of the primary tumour in patients with incurable stage IV colorectal cancer.

BACKGROUND: Excision of primary colorectal cancer associated with irresectable synchronous metastases confers high morbidity and mortality with uncertain benefit. METHODS: For patients with incurable stage IV colorectal cancer, minimally symptomatic primary tumours were left in situ and 5-fluorouracil-based chemotherapy was administered systemically. Primary tumour-specific complications and survival were monitored. RESULTS: There were 13 men and 11 women with primary tumours in the right colon (eight), transverse colon (one), sigmoid colon (eight) or rectum (seven). Eleven patients had metastases limited to the liver (liver replacement less than 25 per cent in one, 25-50 per cent in four and more than 50 per cent in six) and 13 patients had extrahepatic disease (lung or peritoneum). Four patients with sigmoid colon tumours developed bowel obstruction, which required an uncomplicated operation in two and deployment of colonic stents in two patients, at 1, 3, 12 and 20 months from diagnosis. Three further patients underwent right hemicolectomy for abdominal pain of uncertain aetiology, with poor symptomatic relief, and another had a potentially curative operation following disease downstaging. The overall median survival was 10.3 months with a 1-year actuarial survival rate of 44 per cent. CONCLUSION: A policy to defer resection of minimally symptomatic primary colorectal cancer is associated with a low risk of complications before death from progressive systemic disease.

Abdominal Pain↗
PubMed2000

Localization of cyclooxygenase-2 in human sporadic colorectal adenomas.

A putative target for the anti-colorectal cancer action of nonsteroidal anti-inflammatory drugs is the inducible isoform of cyclooxygenase (COX), COX-2. COX-2 is expressed within intestinal adenomas in murine polyposis models, but expression has been poorly characterized in human colorectal neoplasms. Therefore, we investigated the localization of the COX-2 protein in human sporadic colorectal adenomas. Immunohistochemistry for COX-2 and CD68 (a tissue macrophage marker) was performed on formalin-fixed, paraffin-embedded (n = 52) and frozen, acetone-fixed (n = 6) sections of human sporadic colorectal adenomas. Forty of 52 (77%) formalin-fixed adenomas expressed immunoreactive COX-2. COX-2 was localized to superficial interstitial macrophages in 39 cases (75%) and to deep interstitial macrophages in 9 cases (17%). COX-2 staining of dysplastic epithelial cells was observed in 15 cases (29%). A logistic regression analysis identified the adenoma site (P = 0.012) and histological type (P = 0.001) as independent predictors of superficial macrophage COX-2 expression. There was no relationship between the number of macrophages within an adenoma and macrophage COX-2 expression. These results indicate that COX-2 is expressed predominantly by interstitial macrophages within human sporadic colorectal adenomas. If COX-2 does indeed play a role in the early stages of colorectal carcinogenesis in man, these data suggest COX-2-mediated paracrine signaling between the macrophages and epithelial cells within adenomas.

Adenoma↗