Expression of dihydropyrimidine dehydrogenase (DPD) and hENT1 predicts survival in pancreatic cancer.

BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) tumour expression may provide added value to human equilibrative nucleoside transporter-1 (hENT1) tumour expression in predicting survival following pyrimidine-based adjuvant chemotherapy. METHODS: DPD and hENT1 immunohistochemistry and scoring was completed on tumour cores from 238 patients with pancreatic cancer in the ESPAC-3(v2) trial, randomised to either postoperative gemcitabine or 5-fluorouracil/folinic acid (5FU/FA). RESULTS: DPD tumour expression was associated with reduced overall survival (hazard ratio, HR = 1.73 [95% confidence interval, CI = 1.21-2.49], p = 0.003). This was significant in the 5FU/FA arm (HR = 2.07 [95% CI = 1.22-3.53], p = 0.007), but not in the gemcitabine arm (HR = 1.47 [0.91-3.37], p = 0.119). High hENT1 tumour expression was associated with increased survival in gemcitabine treated (HR = 0.56 [0.38-0.82], p = 0.003) but not in 5FU/FA treated patients (HR = 1.19 [0.80-1.78], p = 0.390). In patients with low hENT1 tumour expression, high DPD tumour expression was associated with a worse median [95% CI] survival in the 5FU/FA arm (9.7 [5.3-30.4] vs 29.2 [19.5-41.9] months, p = 0.002) but not in the gemcitabine arm (14.0 [9.1-15.7] vs. 18.0 [7.6-15.3] months, p = 1.000). The interaction of treatment arm and DPD expression was not significant (p = 0.303), but the interaction of treatment arm and hENT1 expression was (p = 0.009). CONCLUSION: DPD tumour expression was a negative prognostic biomarker. Together with tumour expression of hENT1, DPD tumour expression defined patient subgroups that might benefit from either postoperative 5FU/FA or gemcitabine.

Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy.

BACKGROUND: Deoxycytidylate deaminase (DCTD) and ribonucleotide reductase subunit M1 (RRM1) are potential prognostic and predictive biomarkers for pyrimidine-based chemotherapy in pancreatic adenocarcinoma. METHODS: Immunohistochemical staining of DCTD and RRM1 was performed on tissue microarrays representing tumour samples from 303 patients in European Study Group for Pancreatic Cancer (ESPAC)-randomised adjuvant trials following pancreatic resection, 272 of whom had received gemcitabine or 5-fluorouracil with folinic acid in ESPAC-3(v2), and 31 patients from the combined ESPAC-3(v1) and ESPAC-1 post-operative pure observational groups. RESULTS: Neither log-rank testing on dichotomised strata or Cox proportional hazard regression showed any relationship of DCTD or RRM1 expression levels to survival overall or by treatment group. CONCLUSIONS: Expression of either DCTD or RRM1 was not prognostic or predictive in patients with pancreatic adenocarcinoma who had had post-operative chemotherapy with either gemcitabine or 5-fluorouracil with folinic acid.

Venous thromboembolism following colorectal resection.

AIM: The study investigated the rate of significant venous thromboembolism (VTE) following colorectal resection during the index admission and over 1 year following discharge. It identifies risk factors associated with VTE and considers the length of VTE prophylaxis required. METHOD: All adult patients who underwent colorectal resections in England between April 2007 and March 2008 were identified using Hospital Episode Statistics data. They were studied during the index admission and followed for a year to identify any patients who were readmitted as an emergency with a diagnosis of deep venous thrombosis or pulmonary embolism. RESULTS: In all, 35 997 patients underwent colorectal resection during the period of study. The VTE rate was 2.3%. Two hundred and one (0.56%) patients developed VTE during the index admission and 571 (1.72%) were readmitted with VTE. Following discharge from the index admission, the risk of VTE in patients with cancer remained elevated for 6 months compared with 2 months in patients with benign disease. Age, postoperative stay, cancer, emergency admission and emergency surgery for patients with inflammatory bowel disease (IBD) were all independent risk factors associated with an increased risk of VTE. Patients with ischaemic heart disease and those having elective minimal access surgery appear to have lower levels of VTE. CONCLUSION: This study adds to the benefits of minimal access surgery and demonstrates an additional risk to patients undergoing emergency surgery for IBD. The majority of VTE cases occur following discharge from the index admission. Therefore, surgery for cancer, emergency surgery for IBD and those with an extended hospital stay may benefit from extended VTE prophylaxis. This study demonstrates that a stratified approach may be required to reduce the incidence of VTE.

Bile duct reconstruction following laparoscopic cholecystectomy in England.

OBJECTIVES: To determine the incidence of bile duct reconstruction (BDR) following laparoscopic cholecystectomy (LC) and to identify associated risk factors. BACKGROUND: Major bile duct injury (BDI) requiring reconstruction is a serious complication of cholecystectomy. METHODS: All LC and attempted LC operations in England between April 2001 and March 2013 were identified. Patients with malignancy, a stone in bile duct or those who underwent bile duct exploration were excluded. This cohort of patients was followed for 1 year to identify those who underwent BDR as a surrogate marker for major BDI. Logistic regression was used to identify factors associated with the need for reconstruction. RESULTS: In total, 572,223 LC and attempted LC were performed in England between April 2001 and March 2013. Five hundred (0.09 %) of these patients underwent BDR. The risk of BDR is lower in patient that do not have acute cholecystitis [odds ratio (OR) 0.48 (95 % CI 0.30-0.76)]. The regular use of on-table cholangiography (OTC) [OR 0.69 (0.54-0.88)] and high consultant caseload >80 LC/year [OR 0.56 (0.39-0.54)] reduced the risk of BDR. Patients who underwent BDR were 10 times more likely to die within a year than those who did not require further surgery (6 vs. 0.6 %). CONCLUSIONS: The rate of BDR following laparoscopic cholecystectomy in England is low (0.09 %). The study suggests that OTC should be used more widely and provides further evidence in support of the provision of LC services by specialised teams with an adequate caseload (>80).

Hemiarthroplasty using cemented or uncemented stems of proven design: a comparative study.

National Institute of Clinical Excellence guidelines state that cemented stems with an Orthopaedic Data Evaluation Panel (ODEP) rating of > 3B should be used for hemiarthroplasty when treating an intracapsular fracture of the femoral neck. These recommendations are based on studies in which most, if not all stems, did not hold such a rating. This case-control study compared the outcome of hemiarthroplasty using a cemented (Exeter) or uncemented (Corail) femoral stem. These are the two prostheses most commonly used in hip arthroplasty in the UK. Data were obtained from two centres; most patients had undergone hemiarthroplasty using a cemented Exeter stem (n = 292/412). Patients were matched for all factors that have been shown to influence mortality after an intracapsular fracture of the neck of the femur. Outcome measures included: complications, re-operations and mortality rates at two, seven, 30 and 365 days post-operatively. Comparable outcomes for the two stems were seen. There were more intra-operative complications in the uncemented group (13% vs 0%), but the cemented group had a greater mortality in the early post-operative period (n = 6). There was no overall difference in the rate of re-operation (5%) or death (365 days: 26%) between the two groups at any time post-operatively. This study therefore supports the use of both cemented and uncemented stems of proven design, with an ODEP rating of 10A, in patients with an intracapsular fracture of the neck of the femur.

Biliary boulders.

OBJECTIVE: To examine the outcome of endoscopic retrograde cholangiopancreatography (ERCP) in the management of common bile duct (CBD) stones. DESIGN: A retrospective review of 100 consecutive ERCPs performed for CBD stones. RESULTS: 100 ERCPs were performed on 84 patients with a median cohort age of 77. Completion in this cohort, as defined by duct clearance, was achieved in 65% of cases. Completion rates fell rapidly after two ERCPs. 33% of the cohort had small stones <10 mm, and 67% had stones >10 mm. Size, but not number of stones, affected the completion rate and frequency of complications (16%). Presence of periampullary diverticulum did not affect completion or complication rates. MR cholangiopancreatography (MRCP) had a 90% sensitivity for detecting CBD stones compared with 56% for CT. DISCUSSION AND CONCLUSIONS: ERCP remains a high-risk procedure with a significant complication rate when performed to deal with CBD stones. MRCP should be the second choice of investigation for CBD stones. This cohort had an unusually high number of larger stones at ERCP of 67% compared with other published UK cohorts of 8%, and this was reflected in the completion and complication rate.

Definitive management of gallstone pancreatitis in England.

INTRODUCTION: The aim of this study was to investigate whether definitive treatment of gallstone pancreatitis (GSP) by either cholecystectomy or endoscopic sphincterotomy in England conforms with British Society of Gastroenterology (BSG) guidelines and to validate these guidelines. METHODS: Hospital Episode Statistics data were used to identify patients admitted for the first time with GSP between April 2007 and April 2008. These patients were followed until April 2009 to identify any who underwent definitive treatment or were readmitted with a further bout of GSP as an emergency. RESULTS: A total of 5,454 patients were admitted with GSP between April 2007 and April 2008, of whom 1,866 (34.2%) underwent definitive treatment according to BSG guidelines, 1,471 on the index admission. Patients who underwent a cholecystectomy during the index admission were less likely to be readmitted with a further bout of GSP (1.7%) than those who underwent endoscopic sphincterotomy alone (5.3%) or those who did not undergo any form of definitive treatment (13.2%). Of those patients who did not undergo definitive treatment before discharge, 2,239 received definitive treatment following discharge but only 395 (17.6%) of these had this within 2 weeks. Of the 505 patients who did not undergo definitive treatment on the index admission and who were readmitted as an emergency with GSP, 154 (30.5%) were admitted during the 2 weeks immediately following discharge. CONCLUSIONS: Following an attack of mild GSP, cholecystectomy should be offered to all patients prior to discharge. If patients are not fit for surgery, an endoscopic sphincterotomy should be performed as definitive treatment.

Conversion after laparoscopic cholecystectomy in England.

BACKGROUND: Laparoscopic cholecystectomy is the procedure of choice for the treatment of symptomatic gallstones. Conversion to open surgery is reported to be necessary in 5-10% of cases. This study aimed to define those factors associated in English hospitals with the need to convert a laparoscopic cholecystectomy to an open procedure. These included patient-related and particularly nonpatient-related factors. METHODS: Using data derived from a national administrative database, Hospital Episode Statistics, patients undergoing cholecystectomy in acute National Health Service (NHS) hospitals in England during the financial years 2004-2006 were studied. The individual surgeon caseload and the hospital conversion rate were calculated using data from the first (baseline) year. Factors affecting the need for conversion were analyzed using data from the second (index) year. RESULTS: The study included 43,821 laparoscopic cholecystectomies undertaken from 2005 to 2006 in English hospitals. The overall conversion rate was 5.2%: 4.6% for elective procedures and 9.4% for emergency procedures. Patient-related factors that were good predictors of conversion included male sex, emergency admission, old age, and complicated gallstone disease (p < 0.001). Nonpatient-related factors that were good predictors of conversion included the laparoscopic cholecystectomy caseload of individual consultant surgeons and the overall hospital conversion rate in the previous year (all p < 0.001). CONCLUSIONS: Conversion after laparoscopic cholecystectomy is less common as consultant caseload increases. This suggests that operation should be undertaken only by surgeons with an adequate caseload. There is a wide variation in conversion rates among hospitals. This has important implications for training as well as for the organization and accreditation of cholecystectomy services on a national basis.

Percutaneous endoscopic gastrostomy tube removal and replacement after "buried bumper syndrome": the simple way.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) feeding tubes are required for an increasing number of patients with long-term nutritional requirements. "Buried bumper syndrome" (BBS) occurs in 2-6% of PEG placements. In the past, this has been a difficult problem to resolve. The authors aimed to design a safe and simple method of dealing with BBS that can be performed by any endoscopist on a routine endoscopic list with the patient under sedation. METHODS: For 6 years, the authors have used a minimally invasive way to deal with BBS. They have successfully treated 20 BBS patients on a routine endoscopy list with the patient under sedation. The existing PEG is divided 5 cm from the skin. A pair of stent-grasping forceps is inserted via the tube. A snare then is passed via the gastroscope, caught in the stent-grasping forceps, and brought out via the PEG tube. Next, the tube is split as deeply as possible into the PEG exit site, and the snare is closed around the tube. Gentle traction is applied along the endoscope, allowing the internal bumper to concertina and pop through the mucosa. Another PEG can now be placed at a separate site, although the authors have successfully used the same tract. RESULTS: All the patients were followed up, with no further problems related to BBS. CONCLUSIONS: The authors' method is a simple way of addressing the difficult BBS problem. It can be used to remove and replace a PEG with a buried bumper on a routine endoscopy list with the patient under sedation.

Management of acute gallbladder disease in England.

BACKGROUND: Recent literature suggests that early laparoscopic cholecystectomy for acute gallbladder disease is safe and efficacious, but few data are available on the management of acute gallbladder disease in England. METHODS: Hospital Episode Statistics data for the years 2003-2005 were obtained from the Department of Health. All patients admitted as an emergency with acute gallbladder disease during the period from April 2003 to March 2004 were included as a cohort. Repeat emergency admissions for acute gallbladder disease, and cholecystectomies performed during the first admission, an emergency readmission or an elective admission were followed up until March 2005. RESULTS: Some 25,743 patients were admitted as an emergency with acute gallbladder disease, of whom 3791 had an emergency cholecystectomy during the first admission (open cholecystectomy (OC) 29.8 per cent, laparoscopic conversion rate (LCR) 10.7 per cent) and 9806 patients had an elective cholecystectomy (OC 11.3 per cent, LCR 8.3 per cent) during the study period. CONCLUSION: Early cholecystectomy for acute gallbladder disease is not widely practised by surgeons in England. Open cholecystectomy is more commonly used in the emergency than in the elective setting. Early laparoscopic cholecystectomy following an emergency admission carries a higher conversion rate than elective cholecystectomy.

Oesophagectomy practice and outcomes in England.

BACKGROUND: The 2001 UK National Health Service guidance on improving outcomes recommended centralization of oesophageal resection. The aim of this study was to analyse national trends in oesophageal resection in England to determine whether centralization has occurred and its impact on outcomes. METHODS: The study used data from Hospital Episode Statistics for 1997-1998 to 2003-2004 and included patients who had resection for oesophageal cancer. The annual hospital volume was grouped into five categories based on the recommendation for annual volume for a designated centre. RESULTS: A total of 11 838 oesophageal resections were performed. The total number of hospitals performing resections decreased, mainly owing to a fall in the number of very low-volume hospitals (117 in 1997 to 45 in 2003). The proportion of resections performed in very high-volume hospitals increased from 17.8 per cent during 1997-1999 to 21.9 per cent during 2002-2003 (P < 0.001). The overall in-hospital mortality rate was 10.1 per cent, with a significant reduction over time (from 11.7 to 7.6 per cent; P < 0.001). The decline in mortality rate may be due to increased numbers of patients undergoing surgery in higher-volume hospitals. There was an increase in the annual number of new patients from 5672 to 6230 during the study, although a fall in the proportion of resections from 31.5 to 26.0 per cent (P < 0.001). CONCLUSION: Centralization and multidisciplinary team expertise partly explain the improvement in mortality rate, but changes in preoperative selection also play a part.

Influence of surgical resection and post-operative complications on survival following adjuvant treatment for pancreatic cancer in the ESPAC-1 randomized controlled trial.

BACKGROUND/AIMS: The influence of type of surgery and occurrence of post-operative complications on survival following adjuvant therapy for pancreatic cancer are uncertain. METHODS: Cox proportional hazard modelling was used to investigate the influence of type of surgery and the presence of complications on survival in conjunction with clinico-pathological variables in the 550 patients of the ESPAC-1 adjuvant randomized controlled trial. RESULTS: Standard Kausch-Whipple (KW) was performed in 282 (54%) patients, 186 (35%) had a pylorus-preserving (PP) KW, 39 (7%) had a distal pancreatectomy and 21 (4%) had a total pancreatectomy. Post-operative complications were reported in 140 (27%) patients. PP-KW patients survived longer with a median (95% CI) survival of 19.9 (17.3, 23.1) months compared to 14.8 (13.0, 16.7) for KW patients (chi(2)(LR) = 15.1, p < 0.001). KW patients were more likely however to have R1 margins (67 (24%) vs. 29 (16%), chi(2) = 4.59, p = 0.032), poorly differentiated tumours (70 (26%) vs. 19 (10%), chi(2) = 18.65, p < 0.001) and positive lymph nodes (165 (60%) vs. 81 (44%), chi(2) = 11.32, p < 0.001). Post-operative complications did not significantly affect survival. Independent prognostic factors were tumour grade, nodal status and tumour size but not type of surgery or post-operative complications. There was a survival benefit for chemotherapy irrespective of the type of surgery or post-operative complications. CONCLUSIONS: The KW and PP-KW procedures did not significantly influence the hazard of death in the presence of tumour staging, demonstrating that ESPAC-1 surgeons showed good judgement in their choice of operation. Post-operative complications did not adversely affect the survival benefit from adjuvant chemotherapy.

Glutathione S-transferase T1 polymorphisms are associated with outcome in colorectal cancer.

Colorectal cancer (CRC) remains a significant cause of mortality accounting for approximately 10% of all deaths from malignancy in the western world. Polymorphism in the glutathione S-transferase GSTT1 gene has been associated with CRC risk in some but not all studies. In this study, we examined associations between GSTT1 genotypes and CRC risk, and prognosis in 361 cases and 881 unrelated controls. GSTT1 null was associated with a small but significant increase in risk (P = 0.0006, odds ratio (OR) = 1.65, 95% confidence interval (CI) = 1.22-2.24). GSTT1 null was also associated with a significantly younger age at diagnosis (mean 65.2 years) compared with GSTT1 A (mean 67.6 years, P = 0.031). There were no significant associations between GSTT1 genotypes and clinical factors (e.g. Dukes stage, differentiation and tumour node metastasis classification) in the total case group. However, following stratification by age (<70 versus > or =70 years at diagnosis), in the patients diagnosed <70 years of age, GSTT1 null was more common in Dukes grade A/B tumours (P = 0.046), stage T1/T2 tumours (P = 0.053) and those with a pushing margin (P = 0.066). We also identified associations between GSTT1 null and increased prevalence of host lymphocyte response, particularly in the younger patients (P = 0.036). Furthermore, GSTT1 null was associated with improved survival in younger patients (P = 0.017, hazards ratio (HR) = 0.52, 95% CI = 0.31-0.89) but poorer survival in older patients (P = 0.017, HR = 1.89, 95% CI = 1.12-3.20). We proposed a model based on the dual functionality of GSTT1 to explain these contrasting results. We suggest that the null genotype is associated with improved immune response in younger patients, but poorer detoxification in older patients. These findings may also provide an explanation for the contrasting finding of other studies on the role of this gene in CRC.

In vivo evaluation of resorbable bone graft substitutes in a rabbit tibial defect model.

Calcium sulfate as a bone graft substitute is rapidly resorbed in vivo releasing calcium ions but fails to provide long-term three-dimensional framework to support osteoconduction. The setting properties of calcium sulfate however allow it to be applied in a slurry form making it easier to handle and apply in different situations. This study examines the in vivo response of calcium sulfate alone and as a carrier for a coralline hydroxyapatite in an established bilateral corticocancellous defect model in rabbits. Defects were filled flush to the anterior cortex with a resorbable porous ceramic alone and in combination with calcium sulfate slurry, calcium sulfate slurry alone or calcium sulfate pellets and examined at time points up to 52 weeks. Specimens where assessed using Faxitron X-ray, light and electron microscopy. Calcium sulfate in either slurry or pellet form does indeed support new bone formation alone however, complete filling of the bone defect is not observed. Calcium sulfate in slurry form does however improve the surgical handling of particulate bone graft substitutes such as Pro Osteon 200 R, which remained as an osteoconductive scaffold for up to 52 weeks and may have played an important role in the ultimate closure of the cortical windows.

Influence of resection margins on survival for patients with pancreatic cancer treated by adjuvant chemoradiation and/or chemotherapy in the ESPAC-1 randomized controlled trial.

OBJECTIVE: To assess the influence of resection margins on survival for patients with resected pancreatic cancer treated within the context of the adjuvant European Study Group for Pancreatic Cancer-1 (ESPAC-1) study. SUMMARY BACKGROUND DATA: Pancreatic cancer is associated with a poor long-term survival rate of only 10% to 15% after resection. Patients with positive microscopic resection margins (R1) have a worse survival, but it is not known how they fare in adjuvant studies. METHODS: ESPAC-1, the largest randomized adjuvant study of resectable pancreatic cancer ever performed, set out to look at the roles of chemoradiation and chemotherapy. Randomization was stratified prospectively by resection margin status. RESULTS: Of 541 patients with a median follow-up of 10 months, 101 (19%) had R1 resections. Resection margin status was confirmed as an influential prognostic factor, with a median survival of 10.9 months for R1 versus 16.9 months months for patients with R0 margins. Resection margin status remained an independent factor in a Cox proportional hazards model only in the absence of tumor grade and nodal status. There was a survival benefit for chemotherapy but not chemoradiation, irrespective of R0/R1 status. The median survival was 19.7 months with chemotherapy versus 14.0 months without. For patients with R0 margins, chemotherapy produced longer survival compared with to no chemotherapy. This difference was less apparent for the smaller subgroup of R1 patients, but there was no significant heterogeneity between the R0 and R1 groups. CONCLUSIONS: Resection margin-positive pancreatic tumors represent a biologically more aggressive cancer; these patients benefit from resection and adjuvant chemotherapy but not chemoradiation. The magnitude of benefit for chemotherapy treatment is reduced for patients with R1 margins versus those with R0 margins. Patients with R1 tumors should be included in future trials of adjuvant treatments and randomization and analysis should be stratified by this significant prognostic factor.

Phenol sulphotransferase SULT1A1*1 genotype is associated with reduced risk of colorectal cancer.

Sulphation is an important detoxification pathway for numerous xenobiotics; however, it also plays an important role in the metabolism and bioactivation of many dietary and environmental mutagens, including heterocyclic amines implicated in the pathogenesis of colorectal and other cancers. A major sulphotransferase (SULT) enzyme in humans, SULT1A1, is polymorphic with the most common variant allele, SULT1A1*2, occurring at a frequency of about 32% in the Caucasian population. This allele codes for an allozyme with low enzyme activity and stability compared to the wild-type (SULT1A1*1) enzyme, and therefore SULT1A1 genotype may influence susceptibility to mutagenicity following exposure to heterocyclic amines and other environmental toxins. Previously, a significant association of SULT1A1*1 genotype with old age has been observed, suggesting a 'chemoprotective' role for the high-activity phenotype. Here we have compared the frequencies of the most common SULT1A1 alleles in 226 colorectal cancer patients and 293 previously described control patients. We also assessed whether SULT1A1 genotype was related to various clinical parameters in the patient group, including Duke's classification, differentiation, site, nodal involvement and survival. There was no significant difference in allele frequency between the control and cancer patient populations, nor was there a significant association with any of the clinical parameters studied. However, when the age-related difference in allele frequency was considered, a significantly reduced risk of colorectal cancer (odds ratio = 0.47; 95% confidence interval = 0.27-0.83; P = 0.009), was associated with homozygosity for SULT1A1*1 in subjects under the age of 80 years. These results suggest that the high activity SULT1A1*1 allozyme protects against dietary and/or environmental chemicals involved in the pathogenesis of colorectal cancer.

Subcellular localisation of cyclin D1 protein in colorectal tumours is associated with p21(WAF1/CIP1) expression and correlates with patient survival.

We investigated the expression of the cell cycle regulatory proteins cyclin D1 and p21(WAF1/CIP1) (p21) in human colorectal carcinomas using immunohistochemistry. Cyclin D1 was not detected in normal colonic epithelium; however, expression was observed in 74/126 (58.7%) of the tumour samples studied. Protein was detected in the nucleus in 22/126 (17.4%) and exclusively in the cytoplasm in 52/126 (41.3%) tumours. Nuclear expression of cyclin D1 was associated with poorly differentiated tumours (p = 0.035) and was more common in right- than in left-sided tumours (p = 0.005). Tumours displaying either, expression of cytoplasmic, (p = 0.05, HR 0.56, 95% CI 0.31-1.0) or nuclear (p = 0.021, HR 0.24, 95% CI 0.07-0.81) cyclin D1 were associated with improved patient survival compared with tumours negative for cyclin D1. p21 protein was strongly expressed mainly in the upper crypts of normal colonic epithelial cells, but in 63/126 (50%) of the tumour samples studied p21 expression was absent. Patients with tumours in which >50% of cells expressed p21 had improved survival compared to patients whose tumours were negative or had < or =50% of cells expressing p21 (p = 0.06, HR 0.33, 95% CI 0.1-1.0). We also observed a significant association between cyclin D1 subcellular localisation and p21 expression: 21/22 (95.5%) tumours expressing cyclin D1 in the nucleus also expressed p21, whereas only 17/52 (32.7%) of the tumours displaying exclusive cytoplasmic cyclin D1 staining were positive for p21 (p < 0.001). These data highlight the significance of exclusive cytoplasmic expression of cyclin D1 in colorectal cancer and lend support to recent in vitro studies suggesting that p21 protein may modulate the subcellular localisation of the cyclin D1 protein. Thus, deregulated expression of the cyclin D1 and p21 proteins are important in colorectal tumourigenesis and have implications for patient prognosis.

Chronic osteomyelitis. The effect of the extent of surgical resection on infection-free survival.

We studied prospectively a consecutive series of 50 patients with chronic osteomyelitis. Patients were allocated to the following treatment groups: 1) wide resection, with a clearance margin of 5 mm or more; 2) marginal resection, with a clearance margin of less than 5 mm; and 3) intralesional biopsy, with debulking of the infected area. All patients had a course of antibiotics, intravenously for six weeks followed by orally for a further six weeks. No patients in group 1 had recurrence. In patients treated by marginal resection (group 2), 8 of 29 (28%) had recurrence. All patients who had debulking had a recurrence within one year of surgery. We performed a survival analysis to determine the time of the recurrence of infection. In group 2 there was a higher rate of recurrence in type-B hosts (p < 0.05); no type-A hosts had recurrence. This information is of use in planning surgery for chronic osteomyelitis.