The Association of Coloproctology of Great Britain and Ireland consensus guidelines in surgery for inflammatory bowel disease.

AIM: There is a requirement of an expansive and up to date review of surgical management of inflammatory bowel disease (IBD) that can dovetail with the medical guidelines produced by the British Society of Gastroenterology. METHODS: Surgeons who are members of the ACPGBI with a recognised interest in IBD were invited to contribute various sections of the guidelines. They were directed to produce a procedure based document using literature searches that were systematic, comprehensible, transparent and reproducible. Levels of evidence were graded. An editorial board was convened to ensure consistency of style, presentation and quality. Each author was asked to provide a set of recommendations which were evidence based and unambiguous. These recommendations were submitted to the whole guideline group and scored. They were then refined and submitted to a second vote. Only those that achieved >80% consensus at level 5 (strongly agree) or level 4 (agree) after 2 votes were included in the guidelines. RESULTS: All aspects of surgical care for IBD have been included along with 157 recommendations for management. CONCLUSION: These guidelines provide an up to date and evidence based summary of the current surgical knowledge in the management of IBD and will serve as a useful practical text for clinicians performing this type of surgery.

Volume-outcome analysis of colorectal cancer-related outcomes.

BACKGROUND: Significant associations between caseload and surgical outcomes highlight the conflict between local cancer care and the need for centralization. This study examined the effect of hospital volume on short-term outcomes and survival, adjusting for the effect of surgeon caseload. METHODS: Between 1998 and 2002, 8219 patients with colorectal cancer were identified in a regional population-based audit. Outcomes were assessed using univariable and multivariable analysis to allow case mix adjustment. Surgeons were categorized as low (26 or fewer operations annually), medium (27-40) or high (more than 40) volume. Hospitals were categorized as low (86 or fewer), medium (87-109) or high (more than 109) volume. RESULTS: Some 7411 (90.2 per cent) of 8219 patients underwent surgery with an anastomotic leak rate of 2.9 per cent (162 of 5581), perioperative mortality rate of 8.0 per cent (591 of 7411) and 5-year survival rate of 46.8 per cent. Medium- and high-volume surgeons were associated with significantly better operative mortality (odds ratio (OR) 0.74, P = 0.010 and OR 0.66, P = 0.002 respectively) and survival (hazard ratio (HR) 0.88, P = 0.003 and HR 0.93, P = 0.090 respectively) than low-volume surgeons. Rectal cancer survival was significantly better in high-volume versus low-volume hospitals (HR 0.85, P = 0.036), with no difference between medium- and low-volume hospitals (HR 0.96, P = 0.505). CONCLUSION: This study has confirmed the relevance of minimum volume standards for individual surgeons. Organization of services in high-volume units may improve survival in patients with rectal cancer.

Fecal calprotectin predicts the clinical course of acute severe ulcerative colitis.

OBJECTIVES: Calprotectin is a granulocyte neutrophil-predominant cytosolic protein. Fecal concentrations are elevated in intestinal inflammation and may predict relapse in quiescent inflammatory bowel disease. We aim to investigate fecal calprotectin (FC) as a biomarker in predicting the clinical course of acute severe ulcerative colitis (ASUC). METHODS: In 90 patients with ASUC requiring intensive in-patient medical therapy (January 2005-September 2007), we investigated the discriminant ability of FC to predict colectomy and corticosteroid and infliximab nonresponse. All patients received parenteral corticosteroids as first-line treatment; 21 (23.3%) were also treated with infliximab (5 mg/kg), after failure of corticosteroid therapy. RESULTS: Of 90 patients, 31 (34.4%) required colectomy, including 11 (52.4%) of those treated with infliximab. Overall FC was high (1,020.0 microg/g interquartile range: 601.5-1,617.5). FC was significantly higher in patients requiring colectomy (1,200.0 vs. 887.0; P=0.04), with a trend toward significance when comparing corticosteroid nonresponders and responders (1,100.0 vs. 863.5; P=0.08), as well as between infliximab nonresponders and responders (1,795.0 vs. 920.5; P=0.06). Receiver-operator characteristic curve analysis yielded an area under the curve of 0.65 to predict colectomy (P=0.04), with a maximum likelihood ratio of 9.23, specificity 97.4%, and sensitivity 24.0% at a cutoff point of 1,922.5 microg/g. Kaplan-Meier analyses showed that using 1,922.5 microg/g over a median follow-up of 1.10 years, 87% of patients will need subsequent colectomy. CONCLUSIONS: This is the first data set to demonstrate that FC levels are dramatically elevated in severe UC. These data raise the possibility that this biomarker can predict response to first or second-line medical therapy in this setting.

Feature identification and location experiment.

The feature identification and location experiment (FILE) senses radiation from the earth in spectral bands centered at 0.65 and 0.85 micrometers and compares ratios of the reflected solar radiation in the two wavelengths to make real-time classification decisions about four primary features: water, vegetation, bare land, and a cloud-snow-ice class. The radiance ratio classification algorithm successfully made automatic data-selection decisions. The classification image obtained on the mission is providing information needed to evaluate the FILE algorithm and system performance.

Rapid and marked inhibition of rat-liver RNA polymerase by aflatoxin B-1.

From 15 minutes to 2 hours after the administration of aflatoxin B(1) invivo there is a 35-to 70-percent inhibition of DNA-directed RNA synthesis. The inhibition was reversed 12 and 24 hours later.

Involvement of surgical trainees in surgery for colorectal cancer and their effect on outcome.

OBJECTIVE: Surgical training in the UK is undergoing substantial changes. This study assessed: 1) the training opportunities available to trainees in operations for colorectal cancer, 2) the effect of colorectal specialization on training, and 3) the effect of consultant supervision on anastomotic complications, postoperative stay, operative mortality and 5-year survival. METHOD: Unadjusted and adjusted comparisons of outcomes were made for unsupervised trainees, supervised trainees and consultants as the primary surgeon in 7411 operated patients included in the Northern Region Colorectal Cancer Audit between 1998 and 2002. RESULTS: Surgery was performed in 656 (8.8%) patients by unsupervised trainees and in 1578 (21.3%) patients by supervised trainees. Unsupervised operations reduced from 182 (12.4%) in 1998 to 82 (6.1%) in 2002 (P < 0.001). Consultants with a colorectal specialist interest were more likely than nonspecialists to be present at surgical resections (OR 1.35, 1.12-1.63, P = 0.001) and to provide supervised training (OR 1.34, 1.17-1.53, P < 0.001). Patients operated on by unsupervised trainees were more often high-risk patients, however, consultant presence was not significantly associated with operative mortality (OR 0.83, 0.63-1.09, P = 0.186) or survival (HR 1.02, 0.92-1.13, P = 0.735) in risk-adjusted analysis. Supervised trainees had a case-mix similar to consultants, with shorter length of hospital stay (11.4 vs 12.4 days, P < 0.001), but similar mortality (OR 0.90, 0.71-1.16, 0.418) and survival (HR 0.96, 0.89-1.05, P = 0.378). CONCLUSION: One third of patients were operated on by trainees, who were more likely to perform supervised resections in colorectal teams. There was no difference in anastomotic leaks rates, operative mortality or survival between unsupervised trainees, supervised trainees and consultants when case-mix adjustment was applied. This study would suggest that there is considerable underused training capacity available.

Outcomes of the rectal remnant following colectomy for ulcerative colitis.

OBJECTIVE: Controversy surrounds the optimal surgical management of the distal rectal remnant during colectomy for ulcerative colitis (UC) and the potential benefit from the placement of a rectal catheter for remnant drainage. This study reviews the clinical outcomes of patients who have undergone colectomy for UC with intra-peritoneal closure of the rectal remnant. METHOD: Analysis of prospective data lodged on Lothian Surgical Audit databases from patients treated in a tertiary coloproctology unit over 11 years. RESULTS: One hundred and fifty-nine patients were identified, the mean age was 41.9 years, 63% were men. Failure of maximal medical therapy necessitated surgery for 78.1% patients, while 12.6% had acute perforation and 11.9% had toxic megacolon. Complications included five (3.1%) stump dehiscences, eight (5.0%) intra-abdominal/pelvic collections, four (2.5%) significant wound infections, three (1.9%) small bowel obstructions and three (1.9%) deaths. Within the follow-up period, 62.3% patients had an ileo-pouch anal anastomosis (IPAA), 7.5% patients had a completion proctectomy, 10.1% patients within the series had a retained rectal remnant after 1 year follow up, the remaining patients had less than 1 year follow up. CONCLUSION: The intra-peritoneal rectal stump following colectomy for UC is associated with low rates of pelvic sepsis and a high proportion of patients successfully proceeding to IPAA.

Retrospective review of laser therapy for palliation of colorectal tumours.

Patients with inoperable colorectal tumours will often require symptomatic relief due to the nature of extensive disease spread or existing co-morbidities. The use of laser treatment for palliation of tumours in the lower gastrointestinal tract has become an attractive treatment option for such patients. This paper presents the results of a retrospective review of 58 case notes in order to determine the effectiveness of laser therapy in palliating symptoms of colorectal tumours. In addition, the paper aims to identify which colorectal symptoms laser is best used to palliate. The study was conducted in a regional coloproctology unit at the Western General Hospital in Edinburgh. The main findings show that 52% (n=30) of patients had successful (complete/good) resolution of symptoms, 36% (n=21) had a poor response and 12% (n=7) had no resolution of symptoms from laser therapy. Of all documented symptoms, this study found that laser is most effective at palliating obstructive symptoms. It also has beneficial application in the palliation of bleeding and mucous discharge. It is less effective for the anal symptoms of tenesmus and pain and for stool related symptoms such as diarrhoea, constipation, frequency and incontinence.

Variance of surgeons versus pathologists in staging of colorectal cancer.

AIM: Accurate staging of colorectal cancer depends on adequate retrieval and reporting of lymph nodes in the specimen. The presence of positive lymph nodes is an indication for adjuvant therapy. Both surgeons and pathologists influence the number of lymph nodes that are retrieved and reported in specimens. Although several recommendations exist in the literature regarding the minimum number of lymph nodes required for reliable staging, the relationship of examined to infiltrated lymph nodes has not been clarified. The aims of this study were to examine variance among surgeons and pathologists in the retrieval and reporting of lymph nodes in colorectal cancer specimens; to examine the relationship between retrieved/examined lymph nodes and infiltrated lymph nodes; to identify in our own series the minimum number of retrieved lymph nodes required to secure accurate staging. METHODS: Cross-sectional study of 284 patients with colorectal cancer followed in our hospital and retrospective analysis of histopathology reports. Correlation analysis, ANOVA, and survival analysis were performed on the data. RESULTS: There were 127 patients with cancer of the rectum and 157 patients with cancer of the colon under follow-up. The median number of lymph nodes per specimen was 8 (range 0-29). There was no difference in the number of retrieved lymph nodes among 9 surgeons. There were 2 outliers among pathologists, with one reporting a mean of 11.4 (9.8-12.9) 95% CI nodes per specimen and another reporting a mean 4.9 (3.6-6.2) 95% CI nodes per specimen. Dukes and T stage did not affect the number of nodes. Correlation analysis revealed a linear correlation between the total number of reported lymph nodes and the existence of positive lymph nodes. From the correlation equation we calculated that, in order to have one positive node, a minimum of 8.4 nodes was required in the specimen. Therefore, in our group of patients, a minimum of 8.4 nodes was required for accurate Dukes staging. However, survival analysis did not show any difference between patients with more and patients with less than 9 reported lymph nodes. CONCLUSIONS: Variance among pathologists exists and may be at least as important as variance among surgeons. Specialisation of pathologists similar to that of surgeons as well as employment of new techniques may be required . There is a linear correlation between the number of examined lymph nodes and the presence of positive nodes in a colorectal cancer specimen. This linear correlation makes the calculation of the minimum number of lymph nodes possible. In our series a minimum of nine nodes must be examined. However, we have not demonstrated an effect of inadequate nodes numbers on survival, possibly because survival in colorectal cancer is multifactorial.

Inhibition of macromolecular synthesis in L1210 mouse leukemia ascites cells by hycanthone.

Hycanthone inhibits macromolecular synthesis in L1210 cells. At the same concentrations of hycanthone, DNA synthesis is inhibited to a greater extent than the synthesis of RNA. There is an inhibition by the drug of the synthesis of ribosomal precursor RNA; the synthesis of other types of RNA including heterogeneous and small-molecular-weight, also appears to be inhibited. Maturation of 45-S RNA does not seem to be affected, and there is a partial reversal of inhibition of both DNA and RNA synthesis by washing the cells free of hycanthone.

A randomized comparison of tamoxifen with surgical oophorectomy in premenopausal patients with advanced breast cancer.

We randomized 122 premenopausal women to receive tamoxifen or to undergo a surgical oophorectomy. Of 54 evaluable women treated with tamoxifen, 24% had an objective response, as compared with 21% of 53 women having an oophorectomy. The median duration of response for tamoxifen (20 months) was longer than that for surgical oophorectomy (7 months), but this did not achieve statistical significance (P = .056). Overall median survival was 15 months for 58 patients receiving tamoxifen and 25 months for 53 patients undergoing oophorectomy (P = .18). Toxicity was greater in those undergoing oophorectomy, though both treatments were well tolerated. In those premenopausal women for whom hormonal therapy is indicated, tamoxifen is a suitable alternative to surgical oophorectomy.

Differences in Ki67 and c-erbB2 expression between screen-detected and true interval breast cancers.

Breast cancer screening facilitates the early detection of breast cancer, although a significant number of tumors still arise in the interval between screening. The objective of this study was to measure the expression of five markers of proven prognostic significance in symptomatic breast cancer (estrogen receptor, progesterone receptor, p53, Ki67, and c-erbB2) in screen-detected and interval breast cancers to identify biological markers that may be associated with the emergence of symptomatic breast cancer in the screening interval. The expression of estrogen receptor, progesterone receptor, p53, Ki67, and c-erbB2 was assessed in a series of 51 true interval and 84 screened-detected invasive tumors by immunohistochemistry. Interval cancers tended to be of higher histological grade and were of larger pathological size than screen-detected cancers. Expression of estrogen receptor was 1.7-fold lower (P<0.001), whereas expression of p53 was 2.5-fold (P<0.01), Ki67 2.4-fold (P<0.001), and c-erbB2 3.6-fold higher (P<0.01) in true interval cancers compared with screen-detected invasive cancers. There was no significant difference in progesterone receptor expression. The most important differences identified by multiple logistic regression analysis were in the expression of Ki67 and c-erbB2. The differences in the expression of these markers were more important than clinical features such as pathological grade and size. Using the logistic regression model, 83% of the tumors analyzed in this study could be correctly assigned as interval or screen-detected tumors on the basis of Ki67 and c-erbB2 expression. The importance of high expression of Ki67 in interval cancers compared with screen-detected cancers suggests that tumors may become symptomatic in the screening interval as a result of increased levels of cell proliferation. The inclusion of c-erbB2 in the regression equation suggests that this growth factor receptor may play a significant role in stimulating the rapid growth of interval cancers.

Immunohistochemical detection of abnormal cell proliferation in colonic mucosa of subjects with polyps.

Previous studies have shown the presence of increased proliferation in the large bowel epithelium of those at high risk of developing colon cancer. An in vitro technique for labelling large bowel mucosa with the thymidine analogue bromodeoxyuridine (Brdu) was therefore developed and its ability to distinguish differences in mucosal proliferation between subjects with colorectal adenomas and normal controls was assessed. Sigmoid biopsy specimens from 15 subjects with polyps and 15 age and sex matched controls were labelled and the incorporated Brdu visualised with an immunohistochemical technique. Mean labelling index (LI) was significantly higher in those with polyps than in controls. Differences in the pattern of labelling in colonic crypts were compared by the generation of cumulative labelling distributions. Analysis showed a significant expansion of the proliferative compartment in the colon crypts of those with polyps. It is concluded that in vitro labelling with Brdu provides a useful method for the assessment of mucosal proliferation in subjects at high risk of developing colon cancer.

Urine cyclic nucleotide concentrations in cancer and other conditions; cyclic GMP: a potential marker for cancer treatment.

Cyclic guanosine 3',5' monophosphate (cyclic GMP) and cyclic adenosine 3',5' monophosphate (cyclic AMP) have been determined in random urine specimens from 95 healthy individuals, 60 patients with non-cancerous conditions, 52 patients with benign tumours, and 74 patients with malignant tumours. Concentrations of cyclic GMP have also been determined in a number of other groups, including some undergoing cancer treatment. Ninety-three per cent of cancer patients had raised urinary cyclic GMP concentrations compared to the reference range for healthy subjects. For the non-cancerous and benign groups, 33% and 42% respectively had raised concentrations. The urine cyclic AMP concentrations were similar in all groups. Urine cyclic GMP appeared to rise early in the onset of malignant growth. Successful cancer treatment was accompanied by a dramatic fall in the urine cyclic GMP concentrations, whereas if the treatment was unsuccessful the level did not change. It is concluded that urine cyclic GMP may have important applications in the monitoring of cancer treatment.

Activity of ICI 195,739--a novel, orally active bistriazole--in rodent models of fungal and protozoal infections.

ICI 195,739 shows superior potency to other azoles in eliminating vaginal candidosis or dermatophyte infections in animal models of infection by both oral dosing and topical application; effective doses are in the range of 0.5-5.0 mg/kg/day or 0.01-0.30% in a topical formulation. ICI 195,739 is likewise effective in models of systemic fungal infection; 1, 10, 25 mg/kg/day will protect animals given a lethal inoculum of C. albicans, C. neoformans, or A. fumigatus, respectively, as long as dosing is continued, showing activity in this respect superior to that of other azoles tested. ICI 195,739 will suppress infections in mice with T. cruzi and prevent mortality with five daily doses of 1 mg/kg; cure rather than suppression of patent infections has been achieved with 35 daily doses of 10 mg/kg.

Microcomputer applications for primary health care in developing countries.

This article explores some ways in which computer technology can be harnessed to strengthen primary health care planning and management, make more efficient use of scare health resources, and maximize the beneficial impact on health of local, district, and national health systems in both developing and developed countries.

PIP: The special need to work for equity and cost-effectiveness in delivering health services in developing countries sparked the drive for the concepts of primary health care (PHC) and health for all. Planning, managing, monitoring, and evaluating PHC programs calls for data-based methods. As such microcomputer technology is the best way to improve the quality, timeliness, clarity, presentation, and use of relevant information for PHC management. The evolving incorporation of microcomputers in PHC and how they may improve the effectiveness and efficiency of health systems is discussed. Attention is focused upon applications for population-based PHC programs, and excludes consideration of medical offices, laboratories, and hospitals. The role of microcomputers in management information systems (MIS) is discussed at the local, district, provincial, and national levels. Guidelines for strengthening MIS at the 2 former levels are provided, while broader experiences are presented from Papua, New Guinea, Thailand, and the UK. Microcomputer applicability to cost and cost-effectiveness analysis, modeling and simulation for planning and resource allocation, decision-support systems, community health surveys and demographic surveillance, and health research is also discussed. The future of microcomputers in PHC is also considered.

Aggressive local treatment for screen-detected DCIS results in very low rates of recurrence.

AIMS: To review our institution's practice of treatment of a mammographically detected population of ductal carcinoma in situ (DCIS) patients and to determine the outcome. METHODS: Between April 1989 and March 1994, 304 women with median age 59 years (range 51-65) with DCIS detected on screening mammogram, were treated in the Newcastle General and Royal Victoria Infirmary Hospitals, Newcastle-upon-Tyne, UK. More than half of the women (n=176, 57.8%) decided to have mastectomy. Other treatment options were wide local excision (WLE) with radiotherapy (n=97, 32%) and WLE alone (n=31, 10.2%). All except five received adjuvant hormone treatment. RESULTS: Predominant DCIS was comedo in 122 (42%), followed by cribriform in 87 (30%) and micropapillary in 44 (15%) cases. Grade I was found to be commonest grade (54%) followed by grade II (27%) and grade III (11%). With a median follow-up of 88 months, there were six (2%) recurrences, all of which were in women who were given breast conservation treatment, WLE with radiotherapy (n=1, 1%) and without radiotherapy (n=5, 16.6%). Mastectomy in this series was not associated with any recurrence at all. In three cases the recurrence was invasive, one of who also had distant metastasis. CONCLUSIONS: The findings of this study suggest that in women with DCIS suitable for breast conservation, WLE when combined with radiotherapy is associated with a very low recurrence rate.

Serum pyridoxal concentrations in children with diabetes mellitus.

Serum pyridoxal concentrations were measured in 63 children with diabetes mellitus and compared with those in healthy children of the same age. Twenty-four per cent of diabetic children had concentrations below the limit of normal for age and sex. Diabetic children, as a group, had lower serum pyridoxal concentrations than healthy children.

Two types of adriamycin inhibition of a homologous RNA synthesizing system from L1210 cells.

Purified L1210 RNA polymerase II was utilized to study the effect of adriamycin on the kinetics of RNA synthesis. In this study it was found that the adriamycin induced two types of inhibition of RNA synthesis with native DNA as a template. At low drug/DNA-P molar ratios, adriamycin functions as an uncompetitive inhibitor, whereas at high drug/DNA-P molar ratios adriamycin inhibits RNA synthesis competitively. However, when denatured DNA was utilized as template, only competitive inhibition was observed. It is proposed that two modes of inhibition of native DNA-dependent RNA synthesis represents two types of adriamycin-DNA complexes.

Effects of N-trifluoroacetyl adriamycin-14-valerate (AD32) on nuclear RNA synthesis in cultured L1210 cells.

N-Trifluoroacetyl adriamycin-14-valerate (AD32), an analog of adriamycin, inhibits nuclear RNA synthesis. It inhibits rRNA, non-poly(A) hnRNA and poly(A) hnRNA with essentially no effect on smaller nuclear RNA species (< 5S).