An increased prevalence of colorectal neoplasia has been reported in acromegalic patients, and re... more An increased prevalence of colorectal neoplasia has been reported in acromegalic patients, and recommendations have been made for early colonoscopic screening and regular surveillance. This assumption, however, is frequently drawn from studies using selected control populations. To clarify colonoscopic management in these patients, we undertook a 2-center prospective screening colonoscopy study in 122 acromegalics (age range, 25-82 yr). In the absence of ideal age-matched controls, we calculated prevalence rates of occult adenocarcinomas and adenomas in the general population using cumulative data in the published literature from 8 autopsy studies (model 1, n = 3,559) and 4 screening colonoscopy studies (model 2, n= 810), applying linear regression models. Of the 115 patients with complete examinations, adenocarcinomas were discovered in 3 (2.6%), and at least 1 adenoma was found in 11, giving an overall prevalence of neoplasia of 12% (14 of 115). Prevalence rates for age bands 30-40, 40-49, 50-59, 60-69, and 70+ yr were 0%, 8%, 12%, 20%, and 21%, respectively. Compared with the 2 control models, the prevalence of occult colorectal cancer was not significantly increased (acromegalics vs. models 1 and 2, 2.6% vs. 2.3% and 0.9%), nor was there an increase in the prevalence of adenomas in any age band. Pathological characteristics showed some differences, in that adenomas in acromegalics tended to be right sided (68% vs. 57% and 56%), larger (for > or =10 mm, 27% vs. 13% and 9%), and of advanced histology (for tubulovillous, 27% vs. 4% and 22%). No associations were found between the presence of colonic neoplasia and the duration of disease, total GH exposure, cure status, and serum insulin-like growth factor I. This study has failed to demonstrate an increased prevalence of neoplasia in acromegalic patients compared with the expected prevalence in the general population and questions the need for an aggressive colonoscopic screening policy.
CD105 and its ligand transforming growth factor beta (TGFbeta) are modulators of angiogenesis, wh... more 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 ...
Popular reporting of a comparison of cancer survival rates across 17 European countries, based on... more Popular reporting of a comparison of cancer survival rates across 17 European countries, based on data collected by national and regional cancer registries, has left an impression of inadequate treatment of patients in the UK. A subsequent study has suggested that the poor survival rates reported for the UK can, in large part, be explained by more advanced stage at presentation. We believe this conclusion to be unsound and use this study as an example to illustrate the methodological difficulties which may arise during such international comparisons. As the NHS cancer plan aspires to achieve for the UK parity with the best cancer care in Europe, careful thought needs to be given to identifying countries with which the UK can usefully compare itself and the most appropriate indicators for this comparison.
Angiogenesis is essential for tumor growth and metastasis. There are conflicting reports as to wh... more Angiogenesis is essential for tumor growth and metastasis. There are conflicting reports as to whether microvessel density (IMD) in breast cancers is associated with prognosis. This could be due to the use of different antibodies to endothelial cell markers, variation in tissue pretreatment protocols, and nonstandardized counting methods. We have assessed the IMD in 106 breast carcinomas using a pan-endothelial marker, CD34, and a recently described mAb to CD105, which preferentially reacts with endothelial cell in angiogenic tissues. IMD values (separated as above or below median) for CD105 expression showed a statistically significant correlation with overall (P = 0.0029) and disease-free survival (P = 0.0362). In contrast, blood vessel counts using a panendothelial marker CD34 did not correlate with overall or disease-free survival (P = 0.2912 and P = 03153, respectively). When IMD values were subdivided into quartiles and assessed for their prognostic values, there was a statist...
The current use of tumour microvascular density measurements in clinical practice is limited by t... more The current use of tumour microvascular density measurements in clinical practice is limited by the methods employed to identify and quantify the microvessels. The aim of this study was to assess tumour vascularity with three of the most commonly used endothelial markers and with different pre-treatment methods to determine which combination results in the best visualisation of endothelial cells. Serial sections of colorectal carcinoma were treated with microwave oven irradiation, pressure cooking or proteolytic digestion prior to immunostaining with von Willebrand factor (vWf), CD31 or CD34. The sensitivity of staining was enhanced by microwave pre-treatment for CD31 and CD34, and trypsinization for vWf. There was a statistically significant difference between microvascular counts obtained using antibodies for CD34 and vWf (p=0.004), and CD34 and CD31 (p=0.007), but not for CD31 and vWf (p=0.775). We conclude that the use of CD34 antibody on microwaved tissues is the most sensitive method to visualize and quantify vascular density in tumours.
Dear Sir: We recently encountered unusual or-ganelles in a tumor from a 75-year-old white British... more Dear Sir: We recently encountered unusual or-ganelles in a tumor from a 75-year-old white British female presenting with a scalp lesion which histologically was a poorly differentiated malignant neoplasm (Fig. 1). On the basis of histology and im-munohistochemistry [positive staining ...
Background Proper management of patients with inflammatory bowel disease depends upon a definitiv... more Background Proper management of patients with inflammatory bowel disease depends upon a definitive diagnosis, which is best arrived at in the clinicopathological conference (CPC). The aim of the study was to assess the impact of a combined clinical and pathological form called Performa on the definitive diagnostic rate and to see if this improvement was comparable with results achieved with CPCs. Methods Between June 2003 and December 2003, 77 consecutive patients were included in the study. Histological data recorded on the performa were reviewed by one consultant pathologist after the initial reporting to see if there was any change in diagnosis. All cases were also discussed in the CPC as per guidelines. Results The use of the combined form significantly increased the definitive diagnostic rate by decreasing the unclassifiable group by 23.6%, and was comparable to that achieved by CPC. Conclusion In the absence of a CPC, the proposed form is an efficient substitute.
With the aim of resolving the current controversy over the diagnosis and treatment of diverticula... more With the aim of resolving the current controversy over the diagnosis and treatment of diverticular disease, this consensus development conference set out to summarize the actual state of the art. A multidisciplinary panel of international experts (n = 16) was selected to take part in the consensus process. Prior to the conference, all experts were asked to answer a series of questions on diverticular disease. The consensus statement compiled out of these evaluations was modified during a joint meeting of the panel members, then presented for discussion in a public session, and finally revised by the expert panel. The finalized statement was mailed to all panel members for approval (Delphi method). Asymptomatic diverticulosis, diverticular disease (with actual or recurrent symptoms), and complicated diverticular disease were defined separately. No agreement was reached on whether barium enema or colonoscopy is the better choice as an initial diagnostic tool in uncomplicated cases. In complicated cases, computed tomography is recommended for diagnosis. After two attacks of diverticular disease, elective resection should be considered. For patients in whom a concomitant carcinoma cannot be excluded and those with chronic complications (fistula, stenosis, or bleeding) surgery is also indicated. Laparoscopic sigmoid colectomy is recommended only for uncomplicated and, after percutaneous drainage of abscesses, Hinchey stage I and II cases. Laparoscopic surgery has already begun to influence the management of diverticular disease, but the randomized controlled trials needed to support therapy decisions are largely missing.
Eosinophils are a recognized feature of inflammatory bowel disease (IBD), but their tissue distri... more Eosinophils are a recognized feature of inflammatory bowel disease (IBD), but their tissue distribution and functional importance in Crohn's disease (CD) and ulcerative colitis (UC) remain obscure. This study describes an improved immunohistochemical protocol to identify eosinophils in full thickness bowel wall specimens of IBD (n=40) and their in situ relationships with the chemoattractants eotaxin and RANTES. Eosinophils were identified using immunohistochemistry with a combination of monoclonal antibodies (EG1+EG2+MBP), an ultrasensitive technique superior to other methodologies, and their tissue distributions were related to those for eotaxin, RANTES, mast cells and neutrophils. Increased numbers of eosinophils (up to 400 cells/mm 2 ) were observed in active, fulminant inflammation in both CD and UC, this being related to the severity of inflammation and not the diagnosis of the two disorders. The chemoattractants eotaxin (CCL11) and RANTES (CCL5) were upregulated in IBD tissues showing eosinophilia. Neutrophils and mast cells were commonly associated with eosinophil accumulations. Eosinophil numbers and their in situ activation are increased in active rather than chronic IBD. The observations strongly suggest a pivotal role for the eosinophil and its potent mediators in many pathophysiological symptoms of CD and UC, where it represents the major proportion of all granulocytic cells in active inflammatory bowel disease.
An increased prevalence of colorectal neoplasia has been reported in acromegalic patients, and re... more An increased prevalence of colorectal neoplasia has been reported in acromegalic patients, and recommendations have been made for early colonoscopic screening and regular surveillance. This assumption, however, is frequently drawn from studies using selected control populations. To clarify colonoscopic management in these patients, we undertook a 2-center prospective screening colonoscopy study in 122 acromegalics (age range, 25-82 yr). In the absence of ideal age-matched controls, we calculated prevalence rates of occult adenocarcinomas and adenomas in the general population using cumulative data in the published literature from 8 autopsy studies (model 1, n = 3,559) and 4 screening colonoscopy studies (model 2, n= 810), applying linear regression models. Of the 115 patients with complete examinations, adenocarcinomas were discovered in 3 (2.6%), and at least 1 adenoma was found in 11, giving an overall prevalence of neoplasia of 12% (14 of 115). Prevalence rates for age bands 30-40, 40-49, 50-59, 60-69, and 70+ yr were 0%, 8%, 12%, 20%, and 21%, respectively. Compared with the 2 control models, the prevalence of occult colorectal cancer was not significantly increased (acromegalics vs. models 1 and 2, 2.6% vs. 2.3% and 0.9%), nor was there an increase in the prevalence of adenomas in any age band. Pathological characteristics showed some differences, in that adenomas in acromegalics tended to be right sided (68% vs. 57% and 56%), larger (for > or =10 mm, 27% vs. 13% and 9%), and of advanced histology (for tubulovillous, 27% vs. 4% and 22%). No associations were found between the presence of colonic neoplasia and the duration of disease, total GH exposure, cure status, and serum insulin-like growth factor I. This study has failed to demonstrate an increased prevalence of neoplasia in acromegalic patients compared with the expected prevalence in the general population and questions the need for an aggressive colonoscopic screening policy.
CD105 and its ligand transforming growth factor beta (TGFbeta) are modulators of angiogenesis, wh... more 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 ...
Popular reporting of a comparison of cancer survival rates across 17 European countries, based on... more Popular reporting of a comparison of cancer survival rates across 17 European countries, based on data collected by national and regional cancer registries, has left an impression of inadequate treatment of patients in the UK. A subsequent study has suggested that the poor survival rates reported for the UK can, in large part, be explained by more advanced stage at presentation. We believe this conclusion to be unsound and use this study as an example to illustrate the methodological difficulties which may arise during such international comparisons. As the NHS cancer plan aspires to achieve for the UK parity with the best cancer care in Europe, careful thought needs to be given to identifying countries with which the UK can usefully compare itself and the most appropriate indicators for this comparison.
Angiogenesis is essential for tumor growth and metastasis. There are conflicting reports as to wh... more Angiogenesis is essential for tumor growth and metastasis. There are conflicting reports as to whether microvessel density (IMD) in breast cancers is associated with prognosis. This could be due to the use of different antibodies to endothelial cell markers, variation in tissue pretreatment protocols, and nonstandardized counting methods. We have assessed the IMD in 106 breast carcinomas using a pan-endothelial marker, CD34, and a recently described mAb to CD105, which preferentially reacts with endothelial cell in angiogenic tissues. IMD values (separated as above or below median) for CD105 expression showed a statistically significant correlation with overall (P = 0.0029) and disease-free survival (P = 0.0362). In contrast, blood vessel counts using a panendothelial marker CD34 did not correlate with overall or disease-free survival (P = 0.2912 and P = 03153, respectively). When IMD values were subdivided into quartiles and assessed for their prognostic values, there was a statist...
The current use of tumour microvascular density measurements in clinical practice is limited by t... more The current use of tumour microvascular density measurements in clinical practice is limited by the methods employed to identify and quantify the microvessels. The aim of this study was to assess tumour vascularity with three of the most commonly used endothelial markers and with different pre-treatment methods to determine which combination results in the best visualisation of endothelial cells. Serial sections of colorectal carcinoma were treated with microwave oven irradiation, pressure cooking or proteolytic digestion prior to immunostaining with von Willebrand factor (vWf), CD31 or CD34. The sensitivity of staining was enhanced by microwave pre-treatment for CD31 and CD34, and trypsinization for vWf. There was a statistically significant difference between microvascular counts obtained using antibodies for CD34 and vWf (p=0.004), and CD34 and CD31 (p=0.007), but not for CD31 and vWf (p=0.775). We conclude that the use of CD34 antibody on microwaved tissues is the most sensitive method to visualize and quantify vascular density in tumours.
Dear Sir: We recently encountered unusual or-ganelles in a tumor from a 75-year-old white British... more Dear Sir: We recently encountered unusual or-ganelles in a tumor from a 75-year-old white British female presenting with a scalp lesion which histologically was a poorly differentiated malignant neoplasm (Fig. 1). On the basis of histology and im-munohistochemistry [positive staining ...
Background Proper management of patients with inflammatory bowel disease depends upon a definitiv... more Background Proper management of patients with inflammatory bowel disease depends upon a definitive diagnosis, which is best arrived at in the clinicopathological conference (CPC). The aim of the study was to assess the impact of a combined clinical and pathological form called Performa on the definitive diagnostic rate and to see if this improvement was comparable with results achieved with CPCs. Methods Between June 2003 and December 2003, 77 consecutive patients were included in the study. Histological data recorded on the performa were reviewed by one consultant pathologist after the initial reporting to see if there was any change in diagnosis. All cases were also discussed in the CPC as per guidelines. Results The use of the combined form significantly increased the definitive diagnostic rate by decreasing the unclassifiable group by 23.6%, and was comparable to that achieved by CPC. Conclusion In the absence of a CPC, the proposed form is an efficient substitute.
With the aim of resolving the current controversy over the diagnosis and treatment of diverticula... more With the aim of resolving the current controversy over the diagnosis and treatment of diverticular disease, this consensus development conference set out to summarize the actual state of the art. A multidisciplinary panel of international experts (n = 16) was selected to take part in the consensus process. Prior to the conference, all experts were asked to answer a series of questions on diverticular disease. The consensus statement compiled out of these evaluations was modified during a joint meeting of the panel members, then presented for discussion in a public session, and finally revised by the expert panel. The finalized statement was mailed to all panel members for approval (Delphi method). Asymptomatic diverticulosis, diverticular disease (with actual or recurrent symptoms), and complicated diverticular disease were defined separately. No agreement was reached on whether barium enema or colonoscopy is the better choice as an initial diagnostic tool in uncomplicated cases. In complicated cases, computed tomography is recommended for diagnosis. After two attacks of diverticular disease, elective resection should be considered. For patients in whom a concomitant carcinoma cannot be excluded and those with chronic complications (fistula, stenosis, or bleeding) surgery is also indicated. Laparoscopic sigmoid colectomy is recommended only for uncomplicated and, after percutaneous drainage of abscesses, Hinchey stage I and II cases. Laparoscopic surgery has already begun to influence the management of diverticular disease, but the randomized controlled trials needed to support therapy decisions are largely missing.
Eosinophils are a recognized feature of inflammatory bowel disease (IBD), but their tissue distri... more Eosinophils are a recognized feature of inflammatory bowel disease (IBD), but their tissue distribution and functional importance in Crohn's disease (CD) and ulcerative colitis (UC) remain obscure. This study describes an improved immunohistochemical protocol to identify eosinophils in full thickness bowel wall specimens of IBD (n=40) and their in situ relationships with the chemoattractants eotaxin and RANTES. Eosinophils were identified using immunohistochemistry with a combination of monoclonal antibodies (EG1+EG2+MBP), an ultrasensitive technique superior to other methodologies, and their tissue distributions were related to those for eotaxin, RANTES, mast cells and neutrophils. Increased numbers of eosinophils (up to 400 cells/mm 2 ) were observed in active, fulminant inflammation in both CD and UC, this being related to the severity of inflammation and not the diagnosis of the two disorders. The chemoattractants eotaxin (CCL11) and RANTES (CCL5) were upregulated in IBD tissues showing eosinophilia. Neutrophils and mast cells were commonly associated with eosinophil accumulations. Eosinophil numbers and their in situ activation are increased in active rather than chronic IBD. The observations strongly suggest a pivotal role for the eosinophil and its potent mediators in many pathophysiological symptoms of CD and UC, where it represents the major proportion of all granulocytic cells in active inflammatory bowel disease.
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Papers by Najib Haboubi