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The aim of this review was to assess and evaluate reports of studies on the efficacy of anal bulking agents used in the treatment of faecal incontinence. A systematic review of the literature was carried out to identify studies that have reported on the use of anal bulking agents. A variety of biomaterials have been employed for anal bulking. These include autologous fat, bovine glutaraldehyde cross-linked collagen, carbon-coated zirconium oxide beads, dextranomer microspheres in a gel, hydrogel cross-linked with polyacrylamide, polydimethylsiloxane elastomer in a gel, porcine dermal collagen and synthetic calcium hydroxylapatitie ceramic microspheres. Although the ideal site of injection (submucosal or intramuscular) and the mechanism of action remain the subject of debate, most published studies report a significant improvement in continence in at least 50% of subjects with mild to moderate symptoms with little or no associated morbidity.We concluded that anal bulking agents may be used to alleviate symptoms of faecal seepage and soilage.

Purpose: NKG2D (natural killer group 2, member D) binds to cellular ligands of the MIC and ULBP/RAET family. These ligands have restricted expression in normal tissue, but are frequently expressed on primary tumors. The role of NKG2D ligands is thought to be important in carcinogenesis but its prognostic effect has not been investigated in such a large cohort. Experimental Design: In our study, 462 primary colorectal tumors were screened for the expression of all MIC/ULBP/RAET proteins and NK cell infiltration. Tumor microarray technology was used for the purpose of this investigation. Results: NKG2D ligands were expressed by the majority of colorectal tumors; however, the level of expression varied considerably. High expression of MIC (68 versus 56 months) or RAET1G (74 versus 62 months) showed improved patient survival. Tumors expressing high levels of MIC and RAET1G showed improved survival of 77 months over tumors that expressed high levels of one ligand or low levels of both. High-level expression of all ligands was frequent in tumor-node-metastasis stage I tumors, but became progressively less frequent in stages II, III, and IV tumors. Expression of MIC was correlated with NK cellular infiltration. Conclusion: The observations presented are consistent with an immunoediting mechanism that selects tumor cells that have lost or reduced their expression of NKG2D ligands. The combination of MIC and tumor-node-metastasis stage was found to be the strongest predictor of survival, splitting patients into eight groups and suggesting prognostic value in clinical assessment. Of particular interest were stage I patients with low expression of MIC who had a similar survival to stage III patients, and may be candidates for adjuvant therapy. (Clin Cancer Res 2009;15(22):69937002)

Purpose: To assess the tolerability and effectiveness of 105AD7 vaccination in colorectal cancer patients. 105AD7 is a human anti-idiotypic antibody mimicking CD55, a glycoprotein, which is more than expressed on colorectal cancer cells and protects them from attack by complement.Experimental Design: Colorectal cancer patients (n = 67) eligible for primary surgery were randomized to receive the anti-idiotypic antibody 105AD7±Bacillus Calmette-Guerin/alum or to no treatment (control group). The immunizations were given i.d./i.m. before surgery and continued for a period of 2 years. The patients were monitored in enzyme-linked immunospot (ELISPOT; γ-IFN), proliferation assay, and Luminex cytokine assays.Results: No serious adverse events were recorded. Of the 32 investigated immunized patients, 14 (44%) were considered to be responders in the ELISPOT assay. Induced proliferative responses were noted in 17 of 40 (43%) monitored patients. There was no correlation between the ELISPOT and proliferation assays. Luminex analyses revealed tumor necrosis factor-α and granulocyte macrophage colony-stimulating factor responses not only to the vaccine but also toward the native antigen CD55 in 9 of 13 (69%) patients.Conclusions: Immune responses to vaccination were induced in a majority of monitored patients measured by ELISPOT and proliferation assay. The lack of correlation between the ELISPOT and proliferation assays may reflect the fact that the two methods measure different T-cell responses and highlights the importance of multiple readouts in evaluating a potential cancer vaccine. Responses to both the anti-idiotype and the CD55 antigen were measurable, adding support to the use of CD55 as a target in cancer treatment.

INTRODUCTION Information regarding early morbidity, pain and patient satisfaction following band ligation of haemorrhoids is limited. This is the first report to address these issues specifically. PATIENTS AND METHODS A total of 183 patients underwent the procedure over a 10-month period. Prospective data were collected using a detailed structured questionnaire regarding symptoms, analgesia requirements and patient satisfaction in the following week. RESULTS The response rate was 74% (135/183). Pain scores were highest 4 h following the procedure. At 1 week, 75% of patients were pain-free, with 9 (7%) still experiencing moderate-to-severe pain. About 65% required oral analgesia, most frequently on the day of procedure. Rectal bleeding occurred in 86 patients (65%) on the day after banding, persisting in 32 (24%) at 1 week. Vaso-vagal symptoms occurred in 41 patients (30%) and were commonest at the time of banding. Eighty patients (59%) were satisfied with their experience and would undergo the procedure again. Patients requiring oral analgesia and those experiencing bleeding or vaso-vagal symptoms were significantly less likely to be satisfied with the procedure. Only 57% of the patients surveyed would recommend the procedure to a friend. CONCLUSIONS Data from this large cohort of patients suggest that discomfort and bleeding may persist for a week or more following banding of haemorrhoids. Patients should be aware of this in order to make an informed decision as to whether to undergo the procedure, and surgeons should investigate ways of reducing it. Patient satisfaction may be further improved by more accurate counselling regarding the incidence of specific complications.

It has been known for some time that the immune system can recognise growing tumours, and that tumours may respond by modulation of molecules, which make them resistant to further attack. Expression, over-expression, or loss of these molecules may function as markers of tumour progression and prognosis. Among such molecules are the membrane-bound complement regulatory proteins (mCRP), which protect cells from bystander attack by autologous complement. These include CD59 (protectin), which prevents formation of the MAC complex in the terminal stages of complement activation. In the present study, we evaluated immunohistochemical expression of CD59 in a series of over 460 well-characterised colorectal cancers using tissue microarrays (TMA), and related this information to known tumour and patient variables and to survival. The CD59 expression was observed in 69 (15%) of cases overall, and was significantly associated with tumour grade. In contrast, no associations were noted with tumour site, stage or histological type. On survival analysis, a further correlation was observed between expression of CD59 by the colorectal tumours and a reduction in disease-specific patient survival. This observation was strongest for patients with early stage disease. However, a negative impact on survival was also seen in those patients with late stage disease. These results indicate that TMA linked to good clinicopathological databases with good long term follow up are useful tools for determining new prognostic indicators that can be used in future patient management. Immune surveillance may result in immune-editing that induces variable expression of a range of target antigens, and these may be useful prognostic markers. This study has identified CD59 expression as a marker of poor prognosis in colorectal cancer patients.

The aim of this review was to assess and evaluate reports of studies on the efficacy of anal bulking agents used in the treatment of faecal incontinence. A systematic review of the literature was carried out to identify studies that have reported on the use of anal bulking agents. A variety of biomaterials have been employed for anal bulking. These include autologous fat, bovine glutaraldehyde cross-linked collagen, carbon-coated zirconium oxide beads, dextranomer microspheres in a gel, hydrogel cross-linked with polyacrylamide, polydimethylsiloxane elastomer in a gel, porcine dermal collagen and synthetic calcium hydroxylapatitie ceramic microspheres. Although the ideal site of injection (submucosal or intramuscular) and the mechanism of action remain the subject of debate, most published studies report a significant improvement in continence in at least 50% of subjects with mild to moderate symptoms with little or no associated morbidity.We concluded that anal bulking agents may be used to alleviate symptoms of faecal seepage and soilage.

Pseudoaneurysms related to the superior mesenteric artery (SMA) are a recognised complication of trauma to the vessel, and successful treatment with stenting has been previously described. We report the case of a patient who presented with obstruction of the fourth part of the duodenum secondary to a traumatic pseudoaneurysm, a hitherto unreported variant of superior mesenteric artery syndrome. Exclusion of the pseudoaneurysm and relief of the duodenal obstruction were simultaneously achieved by placement of a covered stent.

Background and aims: The putative stem cell marker CD24 is a small, heavily glycosylated, cell surface molecule which was originally associated with tumour metastasis. Recently it has been reported to be upregulated and of prognostic importance in colorectal tumours. The study aims to study the prognostic value of CD24 in a large series of colorectal cancer (CRC). Methods: CD24 protein expression was examined by immunohistochemistry. A total of 10 whole tissue sections (WTS) of adenoma and 345 CRCs arranged as tissue microarrays (TMAs) were evaluated. For comparison with non-neoplastic tissue, 10 WTS containing tumour with associated non-neoplastic tissue were also studied. Results: None of the samples of normal tissue (adjacent to tumour) showed CD24 expression. In the tumours, CD24 expression was seen on the luminal surface of the cells, within the cytoplasm and, unexpectedly, also within the nucleus. Positive immunostaining was seen in 9/10 (90%) adenomas and 313/345 (91%) of CRCs. Weak statistical associations were found between CD24 expression and some clinicopathological features. In contrast to other published studies, however, the analysis did not show any association between CD24 expression and poor prognosis—if anything it was found that loss of CD24 expression appeared to be more related to poor outcome. Conclusion: Upregulation of CD24 is an early and common event during the development of CRC and it may be expressed in any cellular compartment, including the nucleus. CD24 is not, however, a good prognostic marker in CRC.

Cylindrical abdominoperineal excision of the rectum and anus (APER) entails resection of the levator muscles en bloc with the lower rectum and anal canal, thereby reducing the incidence of circumferential resection margin involvement and intra-operative tumour perforations. Options for reconstruction of the resulting defect include myocutaneous flaps, which add significantly to the operating time, or biological tissue grafts. The series of images illustrate our method of tension free repair of the pelvic floor defect with a 7 9 10 cm Surgisis Biodesign 4-layer tissue graft (Figs. 1, 2, 3, 4, 5, 6).

We assessed T-cell responses in young osteosarcoma patients vaccinated with 105AD7, 1-6months after having received chemotherapy. 105AD7 is a human anti-idiotypic antibody mimicking CD55, a glycoprotein that protects from attack by complement and which is overexpressed on osteosarcoma cells. Seven out of 21 investigated patients made a IFN-gamma T-cell response against the vaccine, 105AD7 as assessed by ELISPOT. Cytokine secretion was analysed using Luminex assays and revealed TNF-alpha and GM-CSF responses not only to the vaccine but also towards the native antigen, CD55, in 5 / 14 (36%) of investigated patients. Importantly, the Luminex assay was found to be more sensitive than the more established T-cell assays (ELISPOT and proliferation assay), since responses towards the native antigen were recorded in this assay. Clinical responses and induction of immune responses to both the anti-idiotype and the native CD55 antigen support the use of CD55 as a target in cancer treatment. (c) 2008 Published by Elsevier Inc.

Purpose: Colorectal cancer is one of the most common cancers. The tumor necrosis factor–related apoptosis inducing ligand (TRAIL) pathway transmits apoptotic signals and anticancer agents that activate this system, which are in clinical development. We sought to determine the prognostic value of the clinically most relevant members of this pathway in colorectal cancer patients.Experimental Design: We used an arrayed panel of colorectal cancer tissue to assess the protein expression of the functional TRAIL receptors (TRAIL-R1 and TRAIL-R2) and both the long and short forms of FLICE inhibitory protein (FLIPL and FLIPS). Disease-free survival was examined by Kaplan-Meier estimates and the log-rank test. Prognostic factors were determined by Cox multivariate analysis.Results: The TRAIL receptors and FLIPS were not associated with survival. On univariate analysis, strong FLIPL expression was associated with a significantly higher survival (P = 0.0082). On multivariate analysis using the Cox proportional hazards model, FLIPL phenotype was significantly associated with a poor prognosis in this series (hazard ratio, 2.04; 95% confidence interval, 1.18-3.56; P = 0.011).Conclusions: Overexpression of FLIPL, but not TRAIL-R1 or TRAIL-R2, provides stage-independent prognostic information in colorectal cancer patients. This may indicate a clinically more aggressive phenotype and a subset of patients for whom more extensive adjuvant treatment would be appropriate.

To evaluate the prognostic significance of p27(kip1) in colorectal cancer patients.Cytoplasmic and nuclear p27(kip1) expression was evaluated in 418 colorectal cancers using tissue microarrays. Data were associated with known patient and tumor variables and long-term patient outcomes, providing further insight into the mechanisms by which p27(kip1) may influence tumor development.Nuclear and cytoplasmic p27(kip1) expressions were detected in 59% and 19% of tumors respectively. Cytoplasmic p27(kip1) was almost invariably associated with positive nuclear p27(kip1) expression. Neither case correlated with known clinical or pathological variables, including tumor stage, grade or extramural vascular invasion. Furthermore, nuclear p27(kip1) expression had no impact on survival. However, we identified a significant correlation between expression of cytoplasmic p27(kip1) and longer disease-specific survival times. On multivariate analysis, TNM stage and extramural vascular invasion were highly significant independent prognostic factors, with positive cytoplasmic p27 expression showing a trend towards improved patient survival (P = 0.059).These findings support the recent evidence that cytoplasmic p27(kip1) has a distinct and important biological role that can influence tumor outcome.

The realization of targeted cancer therapy has driven the need to improve selection of patients with colorectal cancer for adjuvant therapy, leading to a search for potential new prognostic markers. There is accumulating evidence that immunosurveillance acts as an extrinsic tumor suppressor. As genetic instability is an early event in colorectal cancer, this can lead to altered expression of molecules conferring resistance to immune attack. Hence, molecules up or downregulated in this process may impact on patient survival. In our study, 449 colorectal tumors were screened for expression of the stress-related protein MICA, which functions as a ligand for the NKG2D receptor and whose expression confers susceptibility to both T- and NK-cell attack. Intensity of MICA expression was quantified using automated image analysis and MICA expression showed no correlation with conventional clinicopathological variables. In contrast, survival analysis showed a significant correlation between higher levels of MICA expression and improved disease-specific survival, with independent prognostic significance in multivariate analysis. Thus, patients with low levels of MICA and a poor prognosis may be good candidates for aggressive chemotherapy. In contrast, patients with high expression of MICA may be candidates for the antibody therapies, as they should be susceptible to NK killing by antibody dependent cellular cytotoxicity.

Background The natural history of anal intraepithelial neoplasia (AIN) is uncertain. This makes management problematic as treatment options to eradicate the condition carry morbidity. The authors report their 10-year experience with conservative management of this condition, highlighting the lessons learnt. Methods All patients were diagnosed with high-grade AIN (AIN III) between 1994 and 2003. Diagnosis was by full-thickness biopsy and histopathological examination. Excision of localized lesions was undertaken, and all patients underwent follow-up every 6 months. Prospective data were collected regarding recurrence, postoperative complications and progression to invasive carcinoma. Results Thirty-five patients were followed for a median of 63 (range 14–120) months. Excision of localized high-grade AIN was carried out in 28 patients with minimal morbidity. Six patients were systemically immunosuppressed at diagnosis, all of whom had multifocal perianal lesions. Three immunosuppressed patients developed invasive anal squamous carcinoma during follow-up. By contrast, no invasive carcinomas were identified among immunocompetent patients with either localized or multifocal perianal disease. Conclusion AIN III appears to have a relatively low potential for malignant transformation in the immunocompetent patient. However, immunosuppressed patients are more likely to have extensive AIN III and a greater risk of malignant change.

Background Advances in our understanding of the molecular biology of colorectal cancer have fuelled the search for novel molecular prognostic markers to complement existing staging systems. Markers assessed in combination may perform better than those considered individually. Using high-throughput tissue microarray technology, we describe the prognostic value of combined p53 / Bcl-2 status in colorectal cancer. Patients and methods Tumour samples from 462 patients who underwent elective surgery to resect a primary colorectal cancer between 1994 and 2000 (mean follow-up of 75 months) were assembled in tissue microarray format. Clinico-pathological data including tumour grade, stage, vascular invasion status along with disease specific survival data has been collected prospectively. Immunohistochemical analysis of p53 and Bcl-2 expression was performed using antibodies DO-7 (p53) and 124 (Bcl-2), and results correlated with known clinico-pathological variables and outcomes. Results Abnormal nuclear p53 accumulation and Bcl-2 overexpression were detected in 221/445 (49.6%) and199/437 (45.5%) tumours respectively, with a significant inverse correlation between the two markers (p = 0.023). On univariate analysis no correlations were found between either marker and standard clinico-pathological variables, however nuclear p53 expression was associated with a significantly reduced survival (p = 0.024). Combined analysis of the two markers indicated that 112/432 (24.2%) cases displayed a p53(-)/Bcl-2(+) phenotype, this occurring more frequently in earlier stage tumours. Kaplan-Meier analysis revealed a significant survival advantage in these p53(-)/Bcl-2(+) tumours compared with the remaining cases (p = 0.0032). On multivariate analysis using the Cox proportional hazards model, neither p53 expression nor Bcl-2 expression alone were of independent prognostic significance, however the combined p53(-)/Bcl-2(+) phenotype was significantly associated with a good prognosis in this series (HR 0.659, 95%CI 0.452–0.959, p = 0.029). Conclusion Patient stratification by combined p53 / Bcl-2 phenotype provides stage-independent prognostic information in colorectal cancer. Specifically, that up to a quarter of patients display a good prognosis p53(-)/Bcl-2(+) phenotype. This may indicate a more clinically indolent phenotype and a subset of patients for whom less aggressive adjuvant treatment appropriate.

Many colorectal tumors lose or downregulate cell surface expression of MHC class I molecules conferring resistance to T-cell-mediated attack. It has been suggested that this phenomenon is due to in vivo immune-tumor interactions. However, evidence of the impact of MHC class I loss on outcomes from colorectal cancer is scarce. In our study of more than 450 colorectal cancers in tissue microarray format, we have shown that both high levels of MHC class I expression and absent MHC class I expression are associated with similar disease-specific survival times, possibly due to natural killer cell-mediated clearance of MHC class I-negative tumor cells. However, tumors with low level expression of MHC class I were found to confer a significantly poorer prognosis, retaining independent significance on multivariate analysis. The existence of these poor prognosis tumors, which may avoid both NK- and T-cell-mediated immune surveillance, has important implications for the design of immunotherapeutic strategies in colorectal cancer.

Introduction Many conditions present as groin swellings, in both the elective and emergency setting. The management of these conditions varies widely, thus a prompt and accurate diagnosis is important. Case presentation A 27 year old female presented with an acute painful swelling in her right groin. A preliminary diagnosis of an incarcerated femoral hernia led to urgent surgical exploration. Histology of the excised tissue showed appearances consistent with endometriosis. Conclusion Endometriosis is an unusual cause of an acute groin mass, which should be considered as a differential diagnosis in women of childbearing age.

A 40-year-old man presented to casualty after losing control of a high-performance car and colliding with a tree. The driver was wearing a seat belt and was able to extricate …

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The murine monoclonal CD3 antibody (OKT3) is effective in the treatment of refractory renal and cardiac allograft rejection and holds promise for improving rejection prophylaxis in heart transplantation. Although the administration of OKT3 is associated with many side effects, arteritis has not been previously reported. We report the development of acute necrotizing temporal arteritis associated with the deposition of mouse immunoglobulin G in a heart transplant recipient receiving OKT3 treatment of refractory rejection.

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A case of acute vascular rejection occurring in a cardiac allograft is presented. The rejection was characterized by prominent lymphocytic infiltration of the major coronary arteries in a pattern similar to that observed in acute vascular rejection occurring in renal allografts. Additionally, there was electron microscopic evidence of endothelial damage of smaller vessels. In addition to routine light microscopic evaluation of heart biopsies obtained in this case, immunofluorescent staining of biopsies for IgG, IgM, C3, Clq, fibrinogen, T cells, B cells, and Ia human leukocyte antigen (HLA-DR) was also performed. These studies suggest that antibodies may have been important in the terminal rejection episode described in this case. Furthermore, immunofluorescent staining detected continuing endothelial cell damage, reflected as Ia antigen positivity of allograft blood vessels, despite apparent improvement of rejection as judged by light microscopy.

Cytomegalovirus (CMV) infection is a frequent cause of serious illness in heart transplant patients and may cause life-threatening pneumonia, with a reported mortality of greater than 50%. We investigated the clinical efficacy of a new antiviral agent, 9(1,3-dihydroxy-2-proproxymethyl)-guanine (DHPG) in the treatment of CMV pneumonia in heart transplant patients. Four of these patients with biopsy-proved CMV pneumonia were treated with DHPG, with resolution of pneumonia and no relapse at a mean follow-up period of 21 weeks. DHPG may be useful in the treatment of CMV pneumonia in heart transplant patients.

Corticosteroid maintenance immunosuppression therapy was successfully discontinued in 24 of 46 patients (52%) who underwent orthotopic heart transplantation between March 8, 1985 and September 1, 1986. In the remaining 22 patients three or more rejection episodes occurred within a 4-month period, and these patients were subsequently maintained on low to moderate dosages of corticosteroids. Patients successfully withdrawn from corticosteroid maintenance (group 1) have remained rejection free for 208 +/- 33 days (mean +/- SEM) after discontinuation of the maintenance therapy with corticosteroids, and their immunosuppression therapy has consisted only of cyclosporine (mean overall cumulative dose 198 +/- 11 mg/m2/day [5.17 +/- 0.35 mg/kg/day]) and azathioprine (mean overall cumulative dose 67.7 +/- 5.4 mg/m2/day [1.74 +/- 0.13 mg/kg/day]), with the most recent serum cyclosporine level and white blood cell count being 146 +/- 10 ng/ml and 5400 +/- 200/microliters, respectively. In contrast to the patients who continue to require maintenance therapy with corticosteroids (group 2), group 1 patients developed their first episode of rejection later (46.8 +/- 8.3 days versus 25.4 +/- 6.1 days, p = 0.040) and reject less frequently during the first 4 months after transplantation (1.7 +/- 0.2 episodes versus 2.6 +/- 0.2 episodes, p = 0.005) as well as during the entire follow-up period (0.21 +/- 0.02 episodes/month versus 0.30 +/- 0.02 episodes/month, p = 0.005). The decreased propensity to reject and subsequent corticosteroid discontinuation resulted in a decreased cumulative dose of corticosteroids in group 1 patients (10.9 +/- 1.9 mg prednisone equivalent/m2/day [0.28 +/- 0.04 mg/kg/day] versus 17.0 +/- 1.2 mg prednisone equivalent/m2/day [0.42 +/- 0.04 mg/kg/day], p = 0.011 [p = 0.026]).(ABSTRACT TRUNCATED AT 250 WORDS)

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