Laparoscopic restorative proctocolectomy: safety and critical level of the ileal pouch anal anastomosis.

AIM: The study reports the longer-term results of laparoscopic-assisted restorative proctocolectomy (RPC), with particular reference to safety and the level of the stapled ileal pouch-anal anastomosis (IPAA). METHOD: Data were collected prospectively from all patients who underwent laparoscopic RP from July 2006 to July 2010. In each patient the operation involved the use of a short (6 cm) Pfannenstiel incision to facilitate placement of the linear stapler for anorectal division. RESULTS: Seventy-five patients underwent RPC either with total proctocolectomy (n = 53) or after previous emergency colectomy (n = 22). Early postoperative morbidity occurred in 18 (24%) patients and readmission within 30 days occurred in 18 (24%). Morbidity during follow up developed in 29 (39%). A pouchogram was carried out in all 75 patients before ileostomy closure with an abnormality shown in eight. The median level of the IPAA was at 3.0 cm (1.0-5.0 cm) above the dentate line. At a median of 33 (9-57) months, there has been one case of small bowel obstruction and no incisional hernia. CONCLUSION: In laparoscopic-assisted RPC a limited Pfannenstiel incision allows safe construction of the IPAA at an appropriate level. Laparoscopic RPC is safe and the emerging long-term follow-up data show the benefit of this approach, with very low rates of small bowel obstruction and incisional hernia formation.

Saving the child to save the nation: poverty, whiteness and childhood in the Cape Colony, c.1870-1895.

Children were central to efforts to eradicate white impoverishment in the Cape Colony in the late nineteenth century. The education and training of poor, white children were believed to be the most effective ways of breaking cycles of poverty, and of ensuring continuing white control over the Cape's resources. Yet a closer reading of the evidence presented to the 1894 Labour Commission and the committee appointed to investigate the Destitute Children Relief Bill suggests that this interest in poor, white children also stemmed from concerns about the children themselves. Destitute white children - both male and female - were described, frequently, as representing a threat to the social, moral, and even economic order, and this view of poor white children shaped official responses to white poverty. This concern for white children reflected not solely their status as 'children' - that they represented the colony's future, were fairly malleable, and could be more easily 'reached' by projects and schemes to eradicate white poverty - but also their problematic class position in a colonial racial order that sought their reform, direction and education into acceptable productive citizens.

The current status of laparoscopic surgery for colorectal disease.

Laparoscopic surgery has an expanding role in the management of colorectal disease. As technical expertise has increased, selection of patients for laparoscopic procedures has widened without any commensurate increase in operative or postoperative complications. This article aims to summarise the current status of laparoscopic surgery in colorectal disease with particular reference to colorectal cancer, inflammatory bowel disease, diverticular disease and disorders of the pelvic floor.

Lymphatic vessel density, microvessel density and lymphangiogenic growth factor expression in colorectal cancer.

OBJECTIVE: Microvessel density (MVD) has been studied as a prognostic marker in human cancers. Quantification of lymphatic vessel density (LVD) is now possible by using new antibodies. Expression of the lymphangiogenic growth factors, VEGF-C and VEGF-D, is associated with poorer clinicopathological outcomes in various tumours. The aim of this study was to quantify LVD and MVD in colorectal cancer, determine the relationship between LVD, MVD and clinicopathological variables and examine the relationship between LVD and tumour expression of VEGF-C and VEGF-D. METHOD: Thirty primary colorectal cancers were immunostained for CD34, lymph vessel endothelial hyaluronan receptor-1 (LYVE-1), VEGF-A and VEGF-D using standard techniques. LVD and MVD were determined by Chalkley grid counting. Tumours were assessed for the presence or absence of LYVE-1 positive lymphatics at different areas within the tumour and the tumour was scored for VEGF-C and VEGF-D immunostaining intensity at the invading tumour edge. Non-parametric tests were used for statistical analysis and a P-value of <0.05 was taken as significant. RESULTS: Lymph vessel endothelial hyaluronan receptor-1 was an excellent lymphatic vessel marker. Within normal bowel wall, lymphatic vessels were found rarely in the superficial colonic mucosa, but were numerous in the submucosa and muscularis propria. In the majority of tumours, lymphatic vessels were located in the peri-tumoural area, intra-tumoural vessels were sparse and tended to be narrow with closed lumina. At the invading tumour edge, VEGF-C expression was higher (P = 0.028) and VEGF-D expression lower (P = 0.011), in tumours in which lymphatic vessels were present. No significant differences between LVD and any clinicopathological variable or route of metastasis were identified. CONCLUSION: Lymphatic vessel density and MVD can be quantified in colorectal carcinoma using immunohistochemical techniques. The balance between expression of VEGF-C and VEGF-D at the invading tumour edge may enhance lymphatic metastasis, by promoting tumour lymphangiogenesis or by activation of pre-existing lymphatic vessels. No relationship was identified between LVD and clinicopathological variables.

Computed tomographic colonography (CTC) performance: one-year clinical follow-up.

AIM: Computed tomographic colonography (CTC) represents a valuable advance in imaging technology for patients with colonic symptoms who are unfit for or fail to complete investigation with conventional techniques of colonoscopy or barium enema. The aim of this study was to examine whether CTC was sufficient to exclude colorectal cancer in such a population. As our patients were unfit for or unable to complete conventional investigations, we used 1 year clinical follow-up to exclude colonic malignancy. MATERIALS AND METHODS: CTC examination was performed using multi-slice CT in patients fitting pre-determined criteria. All patients who had completed 12 months of follow-up after CTC were included. Data were extracted from patient records and lack of presentation within the 12 months following a negative CTC was assumed to equate to lack of colorectal cancer at initial investigation. RESULTS: One hundred and twelve patients underwent CTC with a median age of 78 years (range 39-95) and median follow-up of 18 months (range 12-26). CTC detected 7 colorectal cancers, with 3 false positives and 1 false negative, giving a sensitivity of 87.5% and specificity of 97.1% for the detection of colorectal cancer. CONCLUSIONS: CTC is a good imaging tool for the exclusion of colorectal cancer in a population unfit for or unable to complete colonoscopy or barium enema, with reasonable sensitivity and specificity for detection of colorectal cancer. However, the optimum investigative strategy for fitter symptomatic individuals is still debated and should be clarified by the results of ongoing randomised controlled trials.

Impact of laparotomy and liver resection on the peritoneal concentrations of fibroblast growth factor 2, vascular endothelial growth factor and hepatocyte growth factor.

PURPOSE: Some data have suggested that major surgery is associated with the post-operative growth of residual tumour masses but the mechanism of this is unknown. This study was designed to determine the relationship between intraperitoneal (IP) cytokine levels, and laparotomy in benign and malignant settings. METHODS: Intraperitoneal fluid specimens were obtained at the start and at the end of laparotomy in patients with benign conditions (n=10) and in others undergoing resection of hepatic metastases from colorectal cancer (n=10). Using ELISA the concentration of the angiogenic cytokines, HGF, VEGF-A, VEGF-C, VEGF-D and FGF-2 was determined. RESULTS: The data show that in 16 of 20 patients there was a significant increase (P=0.006) in the IP concentration of hepatocyte growth factor (HGF) but not in the other growth factors by the end of the operation. The mean increase in HGF concentration was 821.5 pg/ml (95% CI: 11.0-6,426.0). Neither the groups (malignant and non-malignant) nor the length of operation correlated with greater or lesser increases in HGF. CONCLUSION: The observation that the increase in HGF occurred in both the cancer and non-cancer groups suggests that it is the surgery rather than the disease that is associated with the increased cytokine concentration. As HGF is a potent endothelial, epithelial and mesenchymal mitogen the data highlight HGF as a potential target for anti-cancer treatments in the peri-operative period. However, investigators should closely monitor wound healing as this may be compromised by this new class of drugs.

Pre-operative plasma levels of vascular endothelial growth factor A, C and D in patients with colorectal cancer.

AIMS: Vascular endothelial growth factor (VEGF)-C and VEGF-D are angiogenic and lymphangiogenic members of the VEGF family of growth factors. Increased VEGF-C or VEGF-D expression in human tumours may be associated with lymph-node metastasis and lymphatic invasion. Circulating plasma levels of VEGF-A, VEGF-C and VEGF-D were measured in patients with colorectal cancer, and assessed for their usefulness as a diagnostic tool for determining lymph-node metastasis. MATERIALS AND METHODS: One hundred and twenty patients with colorectal cancer and 50 healthy control patients were included in the study. Plasma growth-factor levels were assessed by enzyme-linked immunosorbent assays. RESULTS: No significant differences in plasma VEGF-C or VEGF-D levels were seen between patients subgrouped by clinicopathological variables. In particular, there were no differences in median plasma VEGF-C or VEGF-D level in patients with and without lymph-node involvement (VEGF-C: 11.2 U/ml [range, 4.9-51.9] vs 9.9 U/ml [4.4-93.4 U/ml]; P = 0.90; VEGF-D: 335 pg/ml [113-1102] vs 316.5 pg/ml [0-1343]; P = 0.68). CONCLUSIONS: Circulating plasma levels of VEGF-C and VEGF-D do not allow pre-operative identification of lymph-node status in patients with colorectal cancer.

The risk of dysplasia and cancer in the ileal pouch mucosa after restorative proctocolectomy for ulcerative proctocolitis is low: a long-term term follow-up study.

AIM: Some of the rare complications reported in patients with an ileopouch anal anastomosis (IPAA) after coloectomy for chronic ulcerative colitis are dysplasia and carcinoma. The supposed pathway is for the ileal pouch mucosa to go through adaptational changes then is to progress through the phases of chronic pouchitis, dysplasia and subsequently to adenocarcinoma. In many of these studies however, the dysplasia-cancer sequence is inconclusive since the carcinoma might have developed from the ileal mucosa itself or from residual viable rectal mucosa left behind. The purpose of this study was therefore to study the long-term ileal mucosal adaptation patterns and the incidence and grading of dysplasia in the ileal pouch mucosa in patients previously operated on for ulcerative proctocolitis. PATIENTS AND METHODS: Forty-five patients who had been operated on with an IPAA (25 males/20 females), with a median age of 54 years (range 34-76), were invited for clinical examination and pouch endoscopy including mucosal biopsies. The duration of their colitis until surgery was median 6 years (range 1-28) and the time median interval from start of disease until time of follow up 24.8 years (range 17-46). Three independent pathologists from two different centres reviewed sequential mucosal biopsies taken from separate sites of the pouch for dysplasia and mucosal adaptation patterns. RESULTS: The type C pattern with a severe inflammation in lamina propria together with severe atrophy of villi, sometimes with ulceration and granulation tissue, was observed by the two pathologists from one centre in 15 of 45 (33.3%) patients and in 11 (24.4%) of 45 by the third pathologist, respectively. As regards dysplasia one pathologist group evaluated 2/45 (4.4%) cases as low-grade dysplasia while the third pathologist considered one of these cases as indefinite for dysplasia and one as reactive. There was in this respect full agreement between the two centres in 43 (95.6%) of 45 cases. Neither high-grade dysplasia nor invasive carcinoma was diagnosed. CONCLUSION: Dysplastic transformation within the ileal pouch mucosa in patients operated for ulcerative proctocolitis is rare even after a long follow-up. These results are reassuring for both patients and surgeons. There seem to be no solid grounds to support routine surveillance for dysplasia in the ileal pouch mucosa in these patients. The surveillance for neoplastic changes in the remaining muscular/epithelial cuff is a separate issue however.

Waiting times for treatment of rectal cancer in North West England.

An interim goal of the NHS National Cancer Plan is that, by 2005, patients with cancer should be treated within one month of diagnosis and within two months from urgent general practitioner referral. Preoperative radiotherapy for rectal cancer reduces the risk of local recurrence and may translate into improved patient survival. We conducted a prospective audit of existing waiting times for preoperative radiotherapy experienced by 65 patients with rectal cancer referred to the Christie Cancer Centre, Manchester, UK, between May and November 2002. The median time between referral from the surgeon to the start of radiotherapy was 40 days (range 11-85). Only 4 patients (6%) received radiotherapy within 28 days of referral by the surgeon. 62 patients (95%) underwent surgery within 14 days of completing radiotherapy. Delays in the provision of preoperative radiotherapy were primarily due to shortages of radiography staff and equipment. Lack of such infrastructure will prove a major stumbling block to achieving the targets of the NHS Cancer Plan.

Vascular endothelial growth factors C and D and lymphangiogenesis in gastrointestinal tract malignancy.

Vascular endothelial growth factor-C (VEGF-C) and VEGF-D are members of the VEGF family of cytokines and have angiogenic and lymphangiogenic actions. In gastric adenocarcinoma, VEGF-C mRNA and tissue protein expression correlate with lymphatic invasion, lymph node metastasis and in some reports, venous invasion and reduced 5-year survival. Patients with gastric adenocarcinomas containing high levels of VEGF-C expression have significantly reduced 5-year survival rates, and VEGF-C expression is an independent prognostic risk factor for death. The role of VEGF-C in oesophageal squamous and colorectal cancer and VEGF-D in colorectal cancer is not clear, with conflicting reports in the published literature. In order to exploit potential therapeutic applications, further research is necessary to define the precise roles of these cytokines in health and disease.

Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis.

CD105 and its ligand transforming growth factor beta (TGFbeta) are modulators of angiogenesis, which drives tumour growth and metastasis. Tumour microvessel density (MVD) has proven to be an important determinant of prognosis. In this study, we have examined the prognostic value of MVD identified using Mabs to the pan-endothelial marker CD34 and to CD105 in 111 patients with colorectal cancer. The Mab to CD105 preferentially reacts with angiogenic endothelial cells. Of the 111 patients studied, 38 were alive and 73 had died of the disease. The median MVD values counted using anti-CD34 and anti-CD105 were 5 (range 1.40-9.00) and 3.10 (range 0.90-8.00), respectively. Kaplan-Meier survival analysis revealed that only MVD values obtained using CD105 Mab correlated with survival. Patients with a high MVD, above the median (3.10), showed the worst prognosis. A similar outcome was observed when MVD was divided into quartiles. In order to ascertain if this strong expression of CD105 in the tumour vasculature is reflected in patients' plasma, circulating levels of CD105, TGFbeta1 and TGFbeta3 together with the receptor-ligand complexes were quantified in patients with colorectal carcinoma and normal controls. Results showed that except for TGFbeta1, the levels of all other molecules were significantly elevated compared with controls. The levels of CD105 were positively correlated with Dukes' stages. A lower TGFbeta1 level was noted in patients with carcinoma over the controls. Furthermore, TGFbeta3 and CD105/TGFbeta3 complexes were markedly lowered in postoperative compared with preoperative plasma samples. Immunostaining revealed that TGFbeta1 was expressed in cancer cells but TGFbeta3 in the stromal cells, whereas CD105 was exclusively expressed in vascular endothelial cells of tumour blood vessels. In conclusion, this study demonstrates that MVD quantified using a Mab to CD105 is an independent prognostic parameter for survival of patients with colorectal cancer, and that plasma levels of CD105, TGFbeta1, TGFbeta3 and CD105/TGFbeta complexes may be useful markers for assessing disease progression. These data have led us to propose that quantification of these determinants may prove useful to monitor therapeutic efficacy in patients with colorectal cancer, especially those who are being treated with antiangiogenic therapies.

Immunodetection and molecular forms of plasma vascular endothelial growth factor-C.

Vascular endothelial growth factor (VEGF)-C is a member of the VEGF family. VEGF-C is involved in developmental lymphangiogenesis and may be important in pathological lymphangiogenesis, lymphatic invasion and metastasis in carcinoma. We describe the development of an indirect enzyme-linked immunosorbent (ELISA) assay for the quantification of VEGF-C in plasma. Capture of VEGF-C was achieved using goat anti-human VEGF-C antibody, followed by detection with rabbit anti-human VEGF-C antibody. The sensitivity of the assay was amplified using the biotin-avidin and enhanced chemiluminescence (ECL) systems. The assay was highly sensitive and reproducible with a detection range of 0.4-100 U/ml and the intra- and inter-assay variations were less than 8%. Substitutional tests demonstrated that the assay was specific for VEGF-C with no cross-reaction with VEGF-A or VEGF-D. Practical application of the assay was evaluated in 41 colorectal cancer patients and 31 controls. Median plasma levels of VEGF-C were 35.0 U/ml (range: 17.4-75.9 U/ml) in colorectal cancer patients in contrast to 11.5 U/ml (range: 5.4-21.5 U/ml) in controls (p<0.001). Moreover, VEGF-C levels tended to be elevated in patients with advanced disease compared to early disease, but this was not statistically significant owing to a relatively small number of patients in each group. Immunoprecipitation and immunoblotting confirmed detection of VEGF-C in plasma and revealed that two forms of VEGF-C were present in the plasma corresponding to approximately 40 and approximately 80 kDa. The measurement of plasma VEGF-C offers opportunities to explore clinical applications in the management of malignancy, in particular in the prediction of lymphatic spread and in other lymphangiogenesis-related diseases.

A survey of emergency vascular service provision.

Recommendations exist for the optimal management of vascular surgical emergency patients. A telephone survey of on-call surgical registrars was performed to assess the current state of emergency vascular service provision across the Wessex and South West regions in the UK. Of the 24 hospitals surveyed, 10 had formal on-call arrangements for vascular surgical cover, 14 had informal arrangements where the general surgical consultant on-call provided cover and could contact a vascular surgeon if they were available and 3 hospitals had no such arrangements. No difficulties had been experienced by the on-call staff surveyed with any of the existing arrangements. Only 5 of the hospitals had formal on-call arrangements for interventional radiologists. We conclude that current emergency vascular service provision is suboptimal compared to national guidelines and patients may be subject to unequitable access to services. This may not be tenable in the new era of clinical governance.

Dysplasia in the ileoanal pouch.

Formation of an ileo-anal pouch is an accepted technique following colectomy in the surgical management of ulcerative colitis (UC) and familial adenomatous polyposis (FAP). The configuration of pouches and anastomotic techniques has varied over the last two decades. The increased use of stapling devices in formation of the pouch-anal anastomosis avoids the need for endoanal mucosal stripping and may contribute to improved functional results, but leaves a 'columnar cuff' of residual rectal mucosa in situ. Concerns regarding the long-term safety of the ileo-anal pouch have been raised by reports of the occurrence of dysplasia in the pouch mucosa and 15 cases of adenocarcinoma. In UC, persistence of underlying disease in the residual rectal mucosa, anal transition zone and columnar cuff provides the site for development of dysplasia and malignancy. Pouchitis is unlikely to be a major cause of dysplasia or malignancy, as long-term follow-up of patients with Koch pouches has demonstrated. In FAP, any persistent rectal mucosa and mucosa of the small intestine is at risk of adenomatous dysplasia due to the genetic alterations causing the disease. Long-term surveillance should focus on all FAP pouch patients, and in UC patients should be directed towards the diagnosis of residual rectal mucosa in the area distal to the pouch anastomosis. Specialist histopathological opinion is essential in the diagnosis of dysplasia in the ileo-anal pouch.

Laparoscopic appendicectomy: safe and useful for training.

Debate exists about the benefits of laparoscopic appendicectomy when compared to a conventional open procedure. The majority of appendices are removed by the open route in the UK. We report a series of 132 cases of suspected appendicitis managed laparoscopically: 112 (85%) of the patients had acute appendicitis, the remaining 20 (15%) had non-appendiceal pathology. The median operative time was 30 min and there were no conversions to an open operative procedure. The median postoperative stay was two days. Complications were seen in two patients. The published evidence comparing laparoscopic and open appendicectomy is contradictory. Our series shows that laparoscopic appendicectomy is a safe procedure with low morbidity; it is also an excellent training tool in laparoscopic technique and, with sufficient experience, takes no longer than an open procedure. Negative appendicocecotomies are most common in women of fertile age and can be associated with significant morbidity; therefore, laparoscopy should be used to make the diagnosis and, if appendicitis is the cause, the appendix could safely be removed laparoscopically. However, the choice between open and laparoscopic procedure is a subjective decision for the patient and their surgeon. Laparoscopic appendicectomy cannot be regarded as the gold standard.

New approach to cervical flexion deformity in ankylosing spondylitis. Case report.

The treatment of cervical fixed flexion deformity in ankylosing spondylitis presents a challenging problem that is traditionally managed by a corrective cervicothoracic osteotomy. The authors report a new approach to this problem that involves performing a two-level osteotomy at the level of maximum spinal curvature, thereby achieving complete anatomical correction in a one-stage procedure. This 48-year-old woman with ankylosing spondylitis presented with a 30-year history of progressive neck deformity that left her unable to see ahead and caused her to experience difficulty eating, drinking, and breathing on exertion. On examination, she exhibited a 90 degrees fixed flexion deformity of the cervical spine, which was maximum at C-4; this was confirmed on imaging studies. A two-level osteotomy was performed at C3-4 and C4-5 around the area of maximum spinal curvature, and the deformity was corrected by extending the head on its axis of rotation through the uncovertebral joints. The spine was stabilized using a Ransford loop. An excellent anatomical position was achieved, as was complete correction of the deformity. A two-level midcervical osteotomy performed at the level of maximum spinal curvature in ankylosing spondylitis enables complete correction of severe fixed flexion deformity in a single procedure. Preservation of the uncovertebral joints allows smooth and safe correction of the deformity about their axis of rotation.