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The serum concentrations of vascular endothelial growth factor (VEGF) were measured by an enzyme linked immunosorbent assay in 51 healthy controls and in 58 patients with pancreatic cancer before and 30 days after surgery. Pancreatic cancer patients had significantly higher serum VEGF levels compared with healthy controls with a significant association between serum VEGF levels, disease stage and the presence of both lymph node and distant metastases. Serum levels of VEGF decreased significantly after radical resection of the tumor. Elevated preoperative serum VEGF level was a significant prognostic factor, although not independent of stage, for patient survival. These findings suggest that serum VEGF concentrations may reflect pancreatic cancer progression and that their determination may be clinically useful.

Objectives To investigate the expression of heat shock protein-70 (HSP-70) in transitional cell bladder cancer and correlate it with normal and inflammatory bladder tissue samples. Methods We used a three-step avidin-biotin method to examine the localization of a rabbit anti-HSP-70 polyclonal antibody in normal (n = 10), inflammatory (n = 10), and malignant (n = 67) bladder tissue samples. Results Fifty-eight percent of the bladder cancer samples and only 10% and 20% of the normal and inflammatory bladder tissue samples, respectively, expressed HSP-70. Localization of the antibody correlated with the grade ( P P P Conclusions HSP-70 is frequently overexpressed by bladder cancer cells and could be used as biochemical marker in patients with bladder cancer.

This study evaluated serum concentrations of soluble cell adhesion molecules in patients with gastric cancer and in healthy control subjects. Our objectives were to correlate these levels with clinicopathological features, established tumor markers, and patient survival, and to assess changes in serum levels of cell adhesion molecules after tumor surgery.The serum concentrations of the adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were investigated by ELISA in 57 gastric cancer patients, both before and 7 days after surgery, and in 47 healthy control subjects.Preoperative serum concentrations of ICAM-1 and VCAM-1 in gastric cancer patients were significantly higher when compared with those of healthy controls, whereas there were no differences regarding serum E-selectin levels. Serum levels of E-selectin, ICAM-1, and VCAM-1 correlated significantly with each other. There was a significant association between preoperative levels of all three adhesion molecules and disease stage, gastric wall invasion, lymph node involvement, and presence of distant metastases. Their concentrations decreased significantly after radical resection of the tumor, whereas they remained almost unchanged in patients with unresectable disease. Elevated preoperative serum levels of E-selectin, ICAM-1, and VCAM-1 levels were found in 24.6%, 33.3%, and 28.1% of patients, respectively. Elevated levels of all three molecules were significant prognostic factors for patient survival but not independent of disease stage.These findings suggest that serum concentrations of E-selectin, ICAM-1, and VCAM-1 may reflect tumor progression and metastasis, and may be clinically useful.

Both tissue c-erbB-2 expression and serum levels the shed protein have been shown to correlate with tumour stage in a range of adenocarcinomas. This study measured serum and urinary c-erbB-2 levels in patients with gastric cancer, assessing their role in cancer-specific survival and the effects of resectional surgery.Serum and urinary c-erbB-2 concentrations were measured with commercial enzyme-linked immunosorbent assay in 41 healthy controls and in 54 gastric cancer patients. Serum and urinary c-erbB-2 levels in cancer patients were determined before and 7 days following tumour surgery.Preoperative serum and urinary c-erbB-2 levels in gastric cancer patients were significantly higher than those in controls although there were no significant associations between these levels and tumour pathology. Serum c-erbB-2 levels decreased significantly after radical resection of the primary tumour and were an independent prognostic factor for survival, whereas there were no changes in urinary c-erbB-2 levels after surgery or an association with patient survival.Gastric cancer patients show higher serum and urinary c-erbB-2 levels compared to healthy controls. Preoperative serum c-erbB-2 concentration decreases significantly after radical resection of the primary tumour and is an independent prognostic factor for patient survival.

Objectives. To investigate the expression of heat shock protein-70 (HSP-70) in transitional cell bladder cancer and correlate it with normal and inflammatory bladder tissue samples. Methods. We used a three-step avidin-biotin method to examine the localization of a rabbit anti-HSP-70 polyclonal antibody in normal (n = 10), inflammatory (n = 10), and malignant (n = 67) bladder tissue samples. Results. Fifty-eight percent of the bladder cancer samples and only 10% and 20% of the normal and inflammatory bladder tissue samples, respectively, expressed HSP-70. Localization of the antibody correlated with the grade (P

OBJECTIVES: This study evaluated serum concentrations of soluble cell adhesion molecules in patients with gastric cancer and in healthy control subjects. Our objectives were to correlate these levels with clinicopathological features, established tumor markers, and patient survival, and to assess changes in serum levels of cell adhesion molecules after tumor surgery. METHODS: The serum concentrations of the adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were investigated by ELISA in 57 gastric cancer patients, both before and 7 days after surgery, and in 47 healthy control subjects. RESULTS: Preoperative serum concentrations of ICAM-1 and VCAM-1 in gastric cancer patients were significantly higher when compared with those of healthy controls, whereas there were no differences regarding serum E-selectin levels. Serum levels of E-selectin, ICAM-1, and VCAM-1 correlated significantly with each other. There was a significant association between preoperative levels of all three adhesion molecules and disease stage, gastric wall invasion, lymph node involvement, and presence of distant metastases. Their concentrations decreased significantly after radical resection of the tumor, whereas they remained almost unchanged in patients with unresectable disease. Elevated preoperative serum levels of E-selectin, ICAM-1 and VCAM-1 levels were found in 24.6%, 33.3%, and 28.1% of patients, respectively. Elevated levels of all three molecules were significant prognostic factors for patient survival but not independent of disease stage. CONCLUSIONS: These findings suggest that serum concentrations of E-selectin, ICAM-1, and VCAM-1 may reflect tumor progression and metastasis, and may be clinically useful. (C) 2003 by Am. Coll. of Gastroenterology.

The serum concentrations of vascular endothelial growth factor (VEGF) were measured by an enzyme linked immunosorbent assay in 51 healthy controls and in 58 patients with pancreatic cancer before and 30 days after surgery. Pancreatic cancer patients had significantly higher serum VEGF levels compared with healthy controls with a significant association between serum VEGF levels, disease stage and the presence of both lymph node and distant metastases. Serum levels of VEGF decreased significantly after radical resection of the tumor. Elevated preoperative serum VEGF level was a significant prognostic factor, although not independent of stage, for patient survival. These findings suggest that serum VEGF concentrations may reflect pancreatic cancer progression and that their determination may be clinically useful. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

The fact that solid tumor growth and metastasis is angiogenesis-dependent 1 suggests a potential value of blood and tissue angiogenic markers as prognostic and survival determinants. Vascular endothelial growth factor (VEGF) is a dimeric, heparin-binding glycoprotein that functions as a potent mitogen of vascular endothelial cells, providing an opportunity for their migration and organization for the neovascularization of micrometastases. 2,3 Vascular endothelial growth factor exists in four isoforms resulting from alternative exon splicing of its ribonucleic acid (RNA) transcript. 4,5 Of these isoforms, only VEGF121 and VEGF165 are secreted in soluble form, with VEGF165 being the predominant soluble isoform. The larger transcripts, (VEGF189 and VEGF206), are bound to heparin-containing proteoglycans in the extracellular matrix. 6 Experimental studies using different approaches clearly demonstrate that VEGF promotes tumor growth, angiogenesis, and metastasis formation. 7–10 Vascular endothelial growth factor expression at both the mRNA and protein level has also been demonstrated in vivo in a variety of gastrointestinal tumors (including gastric cancer 11,12), with the intensity of its immunohistochemical expression reflecting intratumoral microvessel density, the presence of lymph node and hepatic metastases, and cancer-specific survival. 12 Soluble forms of VEGF are also detectable in the serum and other biologic fluids from cancer patients with the most elevated levels being found in disseminated cancer. 13–15 However, there are limited data regarding the clinical and prognostic significance of serum VEGF (sVEGF) levels in gastric cancer patients. In this study, we evaluated sVEGF levels in healthy controls and in gastric cancer patients. We then correlated these levels with clinicopathologic features and patient survival. The effect of surgery on preoperative sVEGF levels was also evaluated.

alpha-Catenin is a member of the E-cadherin-catenin family of adhesion molecules whose role is essential for the function of the E-cadherin complex. In this study, we have evaluated the expression of alpha-catenin but also of the other catenins (beta-, gamma- and p120-catenin) and E-cadherin in invasive breast cancer and statistically analysed these expressions with known clinicopathological parameters, c-erbB-2 oncoprotein expression and patient survival.Abnormal E-cadherin and beta-catenin expression, especially loss of expression, was associated with lobular histological type of breast carcinomas (P=0.03 and P=0.01, respectively). Abnormal E-cadherin and alpha-catenin expression was associated with high histological grade ductal carcinomas (P=0.01 and P=0.03, respectively). Abnormal E-cadherin and beta-catenin expression was correlated with lymph node metastases (P=0.02 and P=0.05, respectively), while abnormal alpha- and beta-catenin were correlated with the advanced stage of the disease (P=0.04 and P=0.05, respectively). Abnormal p120-catenin expression was associated with loss of PR (P=0.008). Survival analysis demonstrated a statistically significant association between abnormal alpha-catenin expression and poor patient survival (P=0.02). When survival analysis was performed according to the different patterns of abnormal expression, statistically significant associations were seen between cytoplasmic alpha- and beta-catenin expression and poor survival (P=0.006 and P=0.04, respectively).alpha-Catenin, especially its cytoplasmic expression, seems to be a more sensitive prognostic marker than the other members of the E-cadherin complex in invasive breast cancer.

The E-cadherin-catenin cell adhesion complex has been implicated in tumour invasion and metastasis. In this study, we evaluated the clinical significance of E-cadherin and catenin expression in pancreatic cancer.The immunohistochemical expression and cellular co-localization of alpha-, beta- and gamma-catenin were investigated in 43 paraffin-embedded specimens of pancreatic cancer. The relationship between their expression and E-cadherin expression, clinicopathological features and prognosis was evaluated.Abnormal alpha-, beta- and gamma-catenin expression was found in 37%, 44% and 40% of cases, respectively. Both alpha-catenin and gamma-catenin expression correlated with disease stage and with lymph node and distant metastases, whereas aberrant beta-catenin expression only correlated with the presence of lymph node metastases. There was a significant and progressive concordance between E-cadherin and alpha-, beta- and gamma-catenin expression patterns, respectively. The expressions of alpha-, beta- and gamma-catenin also significantly correlated with one another. All three catenins, like E-cadherin, were associated with a poor prognosis, but only E-cadherin and alpha-catenin were independent prognostic factors for cancer-specific survival.Changes in catenin expression and pancreatic cancer progression are possibly related events. The expression of E-cadherin and alpha-catenin may add useful new prognostic information.

Aims: alpha-Catenin is a member of the E-cadherin-catenin family of adhesion molecules whose role is essential for the function of the E-cadherin complex. In this study, we have evaluated the expression of alpha-catenin but also of the other catenins (beta-, gamma- and p120-catenin) and E-cadherin in invasive breast cancer and statistically analysed these expressions with known clinicopathological parameters, c-erbB-2 oncoprotein expression and patient survival. Methods and results: Abnormal E-cadherin and beta-catenin expression, especially loss of expression, was associated with lobular histological type of breast carcinomas (P = 0.03 and P = 0.01, respectively). Abnormal E-cadherin and alpha-catenin expression was associated with high histological grade ductal carcinomas (P = 0.01 and P = 0.03, respectively). Abnormal E-cadherin and beta-catenin expression was correlated with lymph node metastases (P = 0.02 and P = 0.05, respectively), while abnormal alpha- and beta-catenin were correlated with the advanced stage of the disease (P = 0.04 and P = 0.05, respectively). Abnormal p120-catenin expression was associated with loss of PR (P = 0.008). Survival analysis demonstrated a statistically significant association between abnormal alpha-catenin expression and poor patient survival (P = 0.02). When survival analysis was performed according to the different patterns of abnormal expression, statistically significant associations were seen between cytoplasmic alpha- and beta-catenin expression and poor survival (P = 0.006 and P = 0.04, respectively). Conclusions: alpha-Catenin, especially its cytoplasmic expression, seems to be a more sensitive prognostic marker than the other members of the E-cadherin complex in invasive breast cancer.

Background: Elevated serum levels of the cell adhesion molecule E-cadherin have been associated with the presence of tissue injury and inflammation. We compared soluble E-cadherin response during laparoscopic and open cholecystectomy. Methods: The E-cadherin response to surgery was studied in 16 patients undergoing laparoscopic cholecystectomy and 12 patients undergoing open cholecystectomy. Serum E-cadherin levels were measured by an enzyme immunoassay (ELISA) preoperatively, 10 and 30 min after the commencement of surgery, and at 6 and 24 h following the operation. Results: Serum E-cadherin levels decreased progressively during laparoscopic cholecystectomy; their concentrations at 24 h after surgery were significantly lower when compared with preoperative values. In the open cholecystectomy group, serum E-cadherin levels did not differ from preoperative values at any time point. Serum E-cadherin concentrations at 24 h after surgery and the cumulative E-cadherin response were significantly higher in the open cholecystectomy group than in the laparoscopic group. Conclusion: Compared with open cholecystectomy, the cumulative E-cadherin response is significantly reduced following laparoscopic cholecystectomy.

Bladder Cancer is the fifth most common cancer in the Western World, with a projected estimate of 55,000 new cases in 2001 in the United States. It accounts for about 6.3 percent of all new cases of cancer amongst men, with the lifetime risk of being diagnosed with bladder cancer around 3.5 percent. In the United Kingdom, bladder cancer is the second most common urological malignancy, with an estimated 13,000 new cases and 5,500 deaths from this disease occurring each year [1].

In this study we measured serum and urinary c-erbB-2 levels in 63 patients with colorectal cancer and 29 healthy controls, assessing their role in cancer-specific survival and the effects of resectional surgery. Serum and urinary c-erbB-2 levels were measured by an enzyme-linked immunosorbent assay, preoperatively and 7 days following tumor resection. Preoperative serum c-erbB-2 concentrations were significantly higher in the cancer patients and correlated with disease stage and the presence of liver metastases. Urinary c-erbB-2 was detected more often in cancer patients, although levels did not differ from controls and there was no association with any clinicopathological variable. Serum c-erbB-2 levels decreased significantly in those patients resected for cure and were an independent prognostic factor for cancer-specific survival with higher preoperative concentrations correlating with worse overall survival. These findings suggest that serum assessment of c-erbB-2 concentration may be valuable in defining colorectal cancer prognosis. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Background. Vascular endothelial growth factor (VEGF) is an angiogenic cytokine involved in the progression of solid tum ors. In this study we evaluated the clinical usefulness of preoperative serum VEGF Concentrations in patients with colorectal cancer The changes in serum VEGF levels after tumor surgery zoo-e also evaluated. Methods. Serum VEGF levels were determined by an enzyme-linked immunosorbent assay in the sera of 61 healthy control subjects and 67 patients with colorectal cancer preopetatively and 7 and 30 days after surgery. Results. Serum VEGF levels in patients with colorectal cancer (median, 492 pg/mL; interquartile range, 281 to 737 pg/mL) were higher (P < .0001) than in control subjects (median, 186 pg/mL; interquartile range, 100 to 273 pg/mL). There was a significant association between serum VEGF levels and disease stage, invasion depth of the tumor the presence of lymph node and distant metastases, and the degree of diffetentiation. Curative but not palliative resection of the primary tumor resulted in a significant decrease of preoperative serum VEGF levels but normalized in only 72% of patients. Failure of a return of VEGF to normal after resection for cure was associated with (in increased although not statistically significant risk of metastasis during follow-up. Univariate analysis showed a lower survival rate jot patients with increased preoperative serum VEGF levels (P < .002). Multivariate regression analysis showed that the prognostic value of serum VEGF level was not independent of tumor stage. Conclusions. These findings suggest that VEGF plays an important role in tumor progression and the formation of distant metastases in colorectal cancer. It is at present unclear whether serial estimation of serum VEGF is clinically useful it the prediction of tumor relapse.

Objective To evaluate the clinical usefulness of serum vascular endothelial growth factor (VEGF) levels in gastric cancer patients. Summary Background Data Vascular endothelial growth factor plays an important role in the formation of new blood vessels involved in the growth and metastatic spread of solid tumors, but there is limited information regarding the clinical significance of serum VEGF levels in cancer patients. Methods Serum VEGF concentrations were measured by an enzyme linked immunosorbent assay in 61 healthy controls and in 58 gastric cancer patients before surgery, and then again at 7 and 30 days after surgery. The association between preoperative serum VEGF levels, clinicopathological features and patient survival, and their changes following surgery were evaluated. Results Serum VEGF levels in gastric cancer patients were significantly higher than those in controls. There was a significant association between serum VEGF levels and disease stage, as well as invasion depth of the tumor and the presence of distant metastases. Serum VEGF levels decreased significantly after radical resection of the primary tumor and increased in patients with unresectable tumors. Multivariate regression analysis showed that serum VEGF level is an independent prognostic factor for survival. Conclusions Serum VEGF levels in gastric patients are significantly higher compared with normal controls and correlate with local tumor extent, disease stage, and the presence of distant metastases. Preoperative serum VEGF concentration decreases significantly after radical resection of the primary tumor and is an independent prognostic factor for patient survival suggesting that determination of serum VEGF levels may be clinically useful.

Mucosal immunology is still poorly understood. Within gut-associated lymphoid tissues the mucosal barrier balances appropriate responsiveness to cognate antigen with physiological tolerance directed towards innocuous haptens and foreign peptides. Immune activity is controlled by the local cytokine microenvironment and by the production of large quantities of surface IgA (sIgA) designed to exclude antigen in the mucus layer.

Background: Elevated serum levels of the cell adhesion molecule E-cadherin have been associated with the presence of tissue injury and inflammation. We compared soluble E-cadherin response during laparoscopic and open cholecystectomy. Methods: The E-cadherin response to surgery was studied in 16 patients undergoing laparoscopic cholecystectomy and 12 patients undergoing open cholecystectomy. Serum E-cadherin levels were measured by an enzyme immunoassay (ELISA) preoperatively, 10 and 30 min after the commencement of surgery, and at 6 and 24 h following the operation. Results: Serum E-cadherin levels decreased progressively during laparoscopic cholecystectomy; their concentrations at 24 h after surgery were significantly lower when compared with preoperative values. In the open cholecystectomy group, serum E-cadherin levels did not differ from preoperative values at any time point. Serum E-cadherin concentrations at 24 h after surgery and the cumulative E-cadherin response were significantly higher in the open cholecystectomy group than in the laparoscopic group. Conclusion: Compared with open cholecystectomy, the cumulative E-cadherin response is significantly reduced following laparoscopic cholecystectomy.

Tumour necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine associated with cancer-related cachexia. In this study we evaluated serum levels of TNF-alpha in pancreatic cancer patients and investigated their relationships to cachexia.Serum TNF-alpha levels were determined in 63 patients with pancreatic cancer using an enzyme immunoassay specific for human TNF-alpha.Serum TNF-alpha levels were detected in 36.5% of patients. Patients with metastatic disease showed significantly higher positive serum TNF-alpha rate compared to those with non-metastatic disease. Patients with detectable serum TNF-alpha levels had significantly lower body weight and body mass index, lower haematocrit and haemoglobin values, and lower serum total protein and albumin levels compared to those with undetectable TNF-alpha levels. Serum TNF-alpha levels were inversely correlated with body weight, body mass index, haematocrit, haemoglobin, and serum protein and albumin levels.TNF-alpha levels are detectable in the serum of pancreatic cancer patients, particularly in those with advanced disease, and these levels correlate with poor nutritional status.

Background. Diagnosis of tuberculosis of the pancreas is often missed, and may present to the clinician as a difficult diagnostic problem. Methods. We report an extremely rare case of a 35-year-old woman who admitted for acute pain in the right upper quadrant, jaundice, fever 38degreesC and chills. During the last 8 mo, she developed increasing fatigue and a weight loss of approx 10 kg. Results. Computed tomography (CT) of the abdomen showed a mass in the head of the pancreas, and upper gastrointestinal endoscopy revealed a stenosis of the second part of duodenum and a pancreaticoduodenum fistula. Frozen sections by direct trucut needle biopsy raised suspicions of a malignancy, and a Whipple procedure was performed as a radical procedure. The final histopathology revealed a chronic granulomatous lesion with caseating necrosis. Mycobacterium of tuberculosis was detected using the polymerase chain reaction-based assay. Conclusion. This unusual case emphasizes that in suspected cases of pancreatic carcinoma with an atypical presentation, an attempt should be made to confirm the diagnosis by CT-guided needle biopsy, or by ultrasound endoscopic fine-needle aspiration.

The serum concentrations oft he cell adhesion molecules E-select in, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 63 patients with colorectal cancer and in 51 controls by an enzyme-linked immunosorbent assay (ELISA). Their relationship to clinicopathological variables and patient survival and changes in their levels after surgery were examined. Colorectal cancer patients showed significantly higher serum levels of E-selectin, ICAM-1 and VCAM-1 compared with healthy controls. There was a significant association between. the serum levels of these molecules, disease stage and the presence of both lymph node and distant metastases. Both ICAM-1 and VCAM-1 levels correlated with serum E-selectin and carcinoembryonic antigen (CEA) levels. Serum levels of all three molecules decreased significantly after radical resection of the tumour. Elevated pre-operative E-selectin. ICAM-1 and VCAM-1 levels were significant prognostic factors, although not independent of stage. for patient survival. These findings suggest that serum concentrations of E-selectin, ICAM-1 and VCAM-1 may reflect tumour progression and metastasis. Since these markers are linked to CEA levels, it is uncertain whether their measurement will prove cost-effective in colorectal cancer management. (C) 2001 Elsevier Science Ltd. All rights reserved.

We report a very rare case of a 36-year-old woman with von Recklinghausen's disease, synchronous carcinoid of the ampulla of Vater and stromal tumour of the jejunum, who presented with gastrointestinal bleeding and jaundice.

Abnormal mucins are overexpressed by many malignant adenocarcinomas. The variation in their expression and glycosylation makes certain immunodominant peptide core epitopes available for immunological recognition. We reviewed the structural differences between "native" mucins and those detected on malignant cells, a knowledge of which would aid in the design of better anti-mucin vaccines for use in several carcinomas. We also considered the character of inducible anti-MUC1 immune responses reported from recent animal experiments as well as the role of MUC1-transgenic animal models in understanding mucin immunoreactivity. We concluded that the provocation of an anti-MUC1 immune response may be used for the development of a vaccine strategy, which holds promise for therapeutic antineoplastic interventions.

p120cas is involved in signal transduction upon src or growth factor stimulation as well as in E-cadherin mediated cell adhesion and may play an important role in carcinogenesis. In this study, we evaluated immunohistochemically the expression and cellular localization of p120cas in 40 gastric, 43 colorectal and 20 pancreatic carcinomas, and examined the relationship between p120cas expression and pathological features. Altered p120cas expression was observed in 70%, 65% and 60% of gastric, colorectal and pancreatic cancers, respectively. The most common abnormality was of cytoplasmic expression associated with loss of membranous distribution found in 37% of gastric, in 25% of colorectal and in 25% of pancreatic cancers. Heterogeneous staining was noted in 15%, 19% and 20%, and complete loss of expression in 18%, 21% and 15% of gastric, colorectal and pancreatic cancers, respectively. There was no correlation between p120cas staining pattern and tumour grade or stage. Aberrant expression of p120cas which may reflect changes in signal transduction pathways occurs frequently in human malignancies.

We report a very rare case of a 36-year-old woman with von Recklinghausen’s disease, synchronous carcinoid of the ampulla of Vater and stromal tumour of the jejunum, who presented with gastrointestinal bleeding and jaundice. (C) 2000 Harcourt Publishers Ltd.

It is now accepted that altered E-cadherin‐catenin complex expression in oesophageal cancer correlates with clinical and pathological parameters, while abnormal E-cadherin expression occurs early in Barrett’s oesophagus. We evaluated immunohistochemically the expression and cellular localization of a-, b-, and g-catenin, and E-cadherin in 5 dysplastic and 26 non-dysplastic cases of Barrett’s oesophagus. Usually all three catenins were localized at the cell membrane, as was E-cadherin. A similar staining pattern for E-cadherin and the catenins was observed in all cases of non-dysplastic Barrett’s syndrome. However, 60% (3:5) of cases with dysplasia showed loss of membranous b-catenin staining and diffuse cytoplasmic distribution, with predominantly nuclear localization in two cases. Membranous staining and concomitant cytoplasmic localization of E-cadherin, a-catenin and g-catenin were seen in one case with abnormal b-catenin immunoreactivity. Our results indicate that altered subcellular distribution of b-catenin occurs frequently in dysplastic Barrett’s oesophagus and possibly reflects the signalling function of this molecule. Recei6ed 4 No6ember 1998 Accepted 10 March 1999

Epithelial cadherin (E-cadherin) is the main cell-cell adhesion molecule in all epithelia. Aberrant expression of this molecule has been implicated in tumor invasion and metastasis. We evaluated E-cadherin expression and cellular localization in colorectal cancer and investigated its relationship to histopathological features.The expression of E-cadherin was evaluated in 57 formalin-fixed, paraffin-embedded specimens of colorectal cancer by immunohistochemistry.In normal colonic mucosa, E-cadherin was expressed uniformly at the cell membrane. Abnormal E-cadherin expression and/or cellular distribution was found in 46% of tumors. There was a significant correlation between E-cadherin expression and tumor grade with a trend towards reduced E-cadherin expression as the tumor grade increased. The association between E-cadherin expression and tumor stage was not significant.Abnormal E-cadherin expression in colorectal cancer correlates with loss of differentiation.

E-cadherin is a calcium-dependent cell-cell adhesion molecule expressed by melanocytes and responsible for their adhesion to keratinocytes in vitro. In this study, the expression of E-cadherin and its associated cytoplasmic proteins alpha-, beta-, and gamma-catenin was evaluated in melanocytic lesions by immunohistochemistry. E-cadherin expression was evaluated in 70 malignant melanomas and the catenins in 35 of these specimens. Twenty benign melanocytic naevi were also evaluated for E-cadherin and catenin expression. In normal epidermis, E-cadherin/catenin immunostaining was localized at the intercellular borders. In melanomas, a differential loss of E-cadherin expression was observed. Membranous E-cadherin staining was absent in dermal nests of melanomas in their radial growth phase and in Clark level II and III lesions, whereas it was present in a high proportion of melanomas in their vertical growth phase, in Clark level IV and V lesions and in metastasizing melanomas. In contrast, superficial compartments of naevi showed membranous E-cadherin immunoreactivity and junctional naevus cell nests displayed heterogeneous or diffuse cytoplasmic staining. Cytoplasmic alpha- and beta-catenin, but not gamma-catenin staining were detected in all benign and malignant lesions. These findings indicate that qualitative changes in the expression and cellular localization of E-cadherin and of alpha-, beta-, and gamma-catenin occur in melanocytic lesions and may reflect different stages in their progression.

p120 is a cytoplasmic molecule closely associated with the Ca(2+)-dependent cell-cell adhesion molecule E-cadherin, by forming complexes between the cytoplasmic domain of E-cadherin and the cytoskeleton. Although it has been shown that loss or downregulation of E-cadherin is associated with an invasive and poorly differentiated phenotype in several tumours, there is very little information available concerning p120 expression in malignant disease. We used an avidin-biotin immunoperoxidase technique to examine the immunoreactivity and cellular localisation of p120 and E-cadherin in 68 transitional cell carcinomas (TCC) and 14 normal bladder biopsies and correlated these results with pathological and clinical parameters. E-cadherin and p120 were expressed in a normal membranous pattern in all normal bladder epithelium specimens. Loss of normal surface E-cadherin and p120 expression was found in 52/68 (76%) and 57/68 (84%) tumours, respectively. There was a significant correlation between the loss of normal membranous expression of p120 and increased grade (P0.001) and T stage (P0.001). The abnormal expression of p120 was correlated with poor survival (P0.05). Our data indicate that the E-cadherin-p120 complex may be a useful prognostic marker in bladder cancer.

E-cadherin is a cell-cell adhesion molecule involved in tumor progression and metastasis. We evaluated the E-cadherin expression pattern in gastric cancer and investigated its relationship to histopathological features.The expression of E-cadherin was evaluated in 83 formalin-fixed, paraffin-embedded specimens of gastric cancer by immunohistochemistry.In benign gastric mucosa, E-cadherin was expressed uniformly at the cell membrane. Abnormal E-cadherin expression with loss of membranous localization was found in 55 (56%) cancer specimens. Aberrant E-cadherin expression was found more often in diffuse (96%) and mixed type tumors (91%) than in intestinal type tumors (47%) (p=0.0001). A significantly higher proportion of signet-ring (84%) and undifferentiated tumors (87%) showed abnormal E-cadherin expression compared with adenocarcinomas with glandular morphology (57%) (p=0.01). There was a significant correlation between abnormal E-cadherin expression and degree of differentiation (p=0.0001), local tumor extent (p=0.002), and the presence of lymph node metastases (p=0.04).Loss of normal E-cadherin expression may serve as a differentiation marker in gastric cancer.

E-cadherin is a cell-cell adhesion molecule involved in tumour invasion and metastasis. We evaluated E-cadherin expression immunohistochemically in 43 formalin-fixed, paraffin-embedded specimens of pancreatic cancer and investigated its relationship to histopathological features. In non-cancerous pancreatic cells E-cadherin immunoreactivity was localized at the cell membrane, particularly at the intercellular junctions. Abnormal E-cadherin expression was found in 18 (42%) cases. A significantly higher proportion of poorly-differentiated tumours (71%) showed abnormal E-cadherin expression compared with moderately (50%) and well (19%) differentiated tumours (P = 0.037). There was a significant correlation between abnormal E-cadherin expression and lymph node involvement (P = 0.013), the presence of distant metastases (P = 0.034) and advanced tumour stage (P = 0.025). These findings suggest that loss of normal E-cadherin expression is involved in the progression of pancreatic cancer.

Catenins are cytoplasmic proteins associated with E-cadherin, the prime mediator of cell-cell adhesion. Perturbation in any of these molecules results in altered intercellular adhesion, cell differentiation, and increased migration. In this study, the expression and cellular localization of catenins and E-cadherin in inflammatory bowel disease were examined. The expression of E-cadherin; alpha-, beta-, and gamma-catenin; and p120 was evaluated immunohistochemically in 31 paraffin-embedded colonic specimens from 21 patients with ulcerative colitis and Crohn's disease. Loss of normal membranous E-cadherin and alpha-catenin staining was detected at the mucosal edges around epithelial ulcerations in all cases of active ulcerative colitis and in 50 per cent of cases with active Crohn's disease. Reduced expression of p120 protein was also found at the margins of ulcerated mucosa in all cases of active ulcerative colitis and in 75 per cent of those with active Crohn's disease. There was a statistically significant correlation between the expression of E-cadherin, alpha-catenin and p120 and disease activity. There were no changes in beta- and gamma-catenin expression in either ulcerative colitis on Crohn's disease. These findings indicate that altered expression of E-cadherin, alpha-catenin, and p120 occurs during mucosal ulceration in inflammatory bowel disease. These changes may be involved in promoting cell migration during epithelial restitution of the gastrointestinal mucosa.

Serum sex hormone levels were measured preoperatively in 57 morbidly obese patients (19 men and 38 premenopausal women) and 12 months after vertical banded gastroplasty. In the male group, there was a significant decrease in estradiol and an increase in follicle-stimulating hormone (FSH), total testosterone and sex-hormone-binding globulin (SHBG). Among female patients, a significant decrease in estradiol, total and free testosterone and an increase in FSH and SHBG was found. Irregular menses present preoperatively in 5 women were corrected after successful weight loss. In conclusion, altered sex hormonal levels and gynecologic abnormalities associated with morbid obesity are corrected with adequate weight loss following vertical banded gastroplasty.

Intestinal trefoil factor (TFF3) is a member of the trefoil family of peptides, which are constitutively expressed in the gastrointestinal tract. TFF3 has been shown to promote migration of intestinal epithelial cells in vitro and to enhance epithelial restitution in vivo. In the present study, we show that the stimulatory effect of TFF3 on the migration of HT29 colonic carcinoma cells requires the perturbation of E-cadherin function, a calcium-dependent cell-cell adhesion molecule in epithelia. A rapid (1 minute) and specific tyrosine phosphorylation of beta-catenin and epidermal growth factor receptor was detected in cells treated with recombinant rat TFF3. No phosphorylation of E-cadherin or alpha-catenin was detected. Tyrosine phosphorylation of beta-catenin was associated with reduced membranous E-cadherin expression, perturbation of intercellular adhesion, and promotion of cell motility. These results suggest that TFF3 enhances cell migration through modulation of E-cadherin/catenin complex function. Tyrosine phosphorylation of beta-catenin and epidermal growth factor receptor seems to be involved in this process.

Serum sex hormone levels were measured preoperatively in 57 morbidly obese patients (19 men and 38 premenopausal women) and 12 months after vertical banded gastroplasty. In the male group, there was a significant decrease in estradiol and an increase in follicle-stimulating hormone (FSH), total testosterone and sex-hormone-binding globulin (SHBG). Among female patients, a significant decrease in estradiol, total and free testosterone and an increase in FSH and SHBG was found. Irregular menses present preoperatively in 5 women were corrected after successful weight loss. In conclusion, altered sex hormonal levels and gynecologic abnormalities associated with morbid obesity are corrected with adequate weight loss following vertical banded gastroplasty.

Background. beta-Endorphin is an endogenous opioid involved in the regulation of food intake and obesity as well as in insulin metabolism, In this study, we investigated glucose-induced beta-endorphin, insulin, and glucose responsiveness in morbidly obese patients and the effect of surgically induced weight loss, Methods. Thirty-two healthy, nondiabetic, morbidly obese patients (body mass index over 40 kg/m(2)) and 32 normal-weight controls were studied. Serum levels of P-endorphin, insulin, and glucose were measured under basal conditions and during an oral glucose tolerance test (OGTT) before and 12 months following vertical banded gastroplasty. Results. Preoperative basal levels of beta-endorphin, insulin, and glucose and their responses during OGTT in obese patients were significantly higher compared with those of controls. After surgery, basal beta-endorphin, insulin, and glucose levels decreased significantly compared with preoperative values. Postoperative basal insulin and glucose levels were similar to those in controls, while beta-endorphin levels remained significantly higher than those of controls. A significant reduction in total responses of beta-endorphin, insulin, and glucose during OGTT was also observed; however, postoperative beta-endorphin and insulin responses remained significantly higher than in controls. Conclusion. Morbidly obese patients have an increased glucose-stimulated response of beta-endorphin, insulin, and glucose which is partially corrected with weight loss following vertical banded gastroplasty. (C) 1998 Academic Press.

E-cadherin maintains the normal differentiated phenotype in epithelial cells; this function is partly mediated by alpha-catenin, which links E-cadherin to the cell cytoskeleton. Dysfunction of E-cadherin in vitro and in vivo is associated with an invasive phenotype. However, the role of alpha-catenin is largely undetermined. We analyzed the expression of E-cadherin and alpha-catenin in prostate cancer to assess the relationship of abnormal expression to stage, grade and survival. E-cadherin expression was evaluated in 99 prostate cancers. In 79 of those specimens, alpha-catenin was also assessed. In benign prostatic epithelium, both E-cadherin and alpha-catenin were expressed uniformly at the cell membrane. Abnormal E-cadherin expression was found in 56% of cancer specimens, whereas alpha-catenin expression was abnormal in 42%. Abnormal expression of each molecule was significantly correlated with Gleason score (P0.0001) and the ratio of resection chippings infiltrated by tumor (P0.0001). E-cadherin expression was also associated with the extent of disease on the initial bone scan (P = 0.017). Univariate analysis showed significantly lower survival rate for patients with abnormal E-cadherin (P = 0.0003) or alpha-catenin expression (P = 0.031). Multivariate regression analysis showed that the prognostic value of E-cadherin was independent of tumor grade but not of metastasis. These results suggest that perturbation of cell-cell adhesion is involved in the progression of prostate cancer and that analysis of E-cadherin expression may be clinically useful.

E-cadherin and its associated cytoplasmic proteins alpha-, beta-, and gamma-catenin and p120 protein play a crucial role in the maintenance of normal tissue architecture. Perturbation in any of these molecules results in loss of intercellular adhesion and cell transformation. In this study, we have used immunohistochemistry to localize E-cadherin, alpha-, beta-, and gamma-catenin, and p120 in paraffin-embedded tissues from 60 patients with colonic polyps. Specimens consisted of 20 samples each from hyperplastic, inflammatory, and sporadic adenomatous polyps. Ten histologically normal colonic samples were also studied. Normal colonic epithelial cells showed strong E-cadherin/ catenin/p120 immunostaining at the cell-cell junction. In 65% (13/20) of adenomatous polyps, beta-catenin showed abnormal nuclear localization with increased expression and loss of membranous staining compared with the adjacent normal mucosa. In two cases (10%), gamma-catenin was seen in the nuclei. Heterogeneous p120 immunoreactivity was observed in four cases (20%), of which two also showed beta-catenin nuclear localization. Preserved membranous alpha-catenin staining was seen in all cases. E-cadherin was down-regulated in 6 of 20 (30%) adenomas with loss of cell surface staining in 3 cases. All hyperplastic and 40% (8/20) of inflammatory polyps showed weak E-cadherin expression on the surface epithelium. Similar changes in p120 expression were seen in all hyperplastic and 20% (4/20) of inflammatory polyps. There were no concomitant changes in alpha-, beta-, or gamma-catenin expression. These results indicate that changes in catenin expression and cellular localization occur early in dysplastic colonic lesions.

A case of gallbladder carcinoma is presented where metastatic tumour developed at the abdominal wall port site following laparoscopic cholecystectomy.

Incidentally discovered adrenal masses are common since the advent and application of sensitive noninvasive imaging methods. The significance of these so-called "incidentalomas" and the question of further evaluation or treatment remains elusive. This report describes a retrospective study of 86 patients with incidentaloma. Adrenalectomy was performed on 26 patients during initial admission. Histologically, two cortisol-producing adenomas, an adenoma with subclinical cortisol production, and two pheochromocytomas (all of the preceding detected during the preoperative hormonal evaluation), three cystic lesions, one myelolipoma, and one hematoma were found. One primary and two metastatic adrenal carcinomas were also found in this series. Sixty patients with a nonfunctioning incidentaloma smaller than 6 cm were observed in an average of 43 months with serial CT scans performed at 3, 9, and 18 months after the initial diagnosis. Enlargement of the mass was detected in two patients; both proved to be nonfunctioning adenomas. Based on these observations, it is concluded that the initial laboratory evaluation is mandatory in cases of incidentalomas, including parameters of adrenocortical and medullar function. Hormonally active incidentalomas and those suspected for malignancy should be treated surgically. Masses greater than 6 cm should also be removed. Smaller incidentalomas without endocrine activity or signs of malignancy should be followed by CT scan at 3, 9, and 18 months after the initial diagnosis.

The expression of oestrogen receptor (ER) protein in invasive carcinoma of the breast and its clinical significance has been extensively evaluated. Little information is available regarding ER expression in ductal carcinoma in situ (DCIS). In this study, 46 formalin-fixed, paraffin-embedded tissue specimens of mammographically detected DCIS were evaluated immunohistochemically for the presence of ER using specific monoclonal antibodies against ER (ER-ICA Abbott Lab). The associations between ER expression and histological type, degree of differentiation and patient menopausal status were evaluated. Positive ER staining was present in 72% of cases. Non-comedo types of DCIS were more frequently ER-positive than comedocarcinoma. ER-positive tumours were inversely correlated with the presence of nuclear pleomorphism. The incidence of ER in pre-menopausal and post-menopausal women was similar. In conclusion, ER expression is present in a considerable percentage of DCIS, and ER-positivity is associated with the degree of differentiation and non-comedo carcinoma variants.

In this prospective, randomized study, we compared 42 patients undergoing laparoscopic cholecystectomy and 40 undergoing open cholecystectomy to determine if laparoscopic cholecystectomy results in less respiratory impairment and fewer respiratory complications. Pulmonary function tests, arterial blood-gas analysis and chest radiographs were obtained in both groups before operation and on the second day after operation. Postoperative pain scores and analgesic requirements were also recorded. After operation, a significant reduction in total lung capacity, functional residual capacity (FRC), forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and mid-expiratory flow (FEF25-75%) occurred after both laparoscopic and open cholecystectomy. The reductions in FRC, FEV1, FVC and FEF25-75% were smaller after laparoscopic (7%, 22%, 19% and 23%, respectively) than after open (21%, 38%, 32% and 34%, respectively) cholecystectomy. Laparoscopic cholecystectomy was also associated with a significantly lower incidence (28.6% vs 62.5%) and less severe atelectasis, better oxygenation and reduced postoperative pain and analgesia use compared with open cholecystectomy. We conclude that postoperative pulmonary function was impaired less after laparoscopic than after open cholecystectomy.

In this prospective, randomized study, we compared 42 patients undergoing laparoscopic cholecystectomy and 40 undergoing open cholecystectomy to determine if laparoscopic cholecystectomy results in less respiratory impairment and fewer respiratory complications. Pulmonary function tests, arterial blood-gas analysis and chest radiographs were obtained in both groups before operation and on the second day after operation. Postoperative pain scores and analgesic requirements were also recorded. After operation, a significant reduction in total lung capacity, functional residual capacity (FRC), forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC) and mid-expiratory flow (FEF(25-75%)) occurred after both laparoscopic and open cholecystectomy. The reductions in FRC, FEV(1), FVC and FEF(25-75%) were smaller after laparoscopic (7%, 22%, 19% and 23%, respectively) than after open (21%, 38%, 32% and 34%, respectively) cholecystectomy. Laparoscopic cholecystectomy was also associated with a significantly lower incidence (28.6% vs 62.5%) and less severe atelectasis, better oxygenation and reduced postoperative pain and analgesia use compared with open cholecystectomy. We conclude that postoperative pulmonary function was impaired less after laparoscopic than after open cholecystectomy.

{Objective. This study was undertaken to assess a potential relationship between idiopathic deep venous thrombosis (DVT) and occult cancer. Design. Prospective study with a 2-year follow-up. Setting. The Angiology Unit of the First Department of Surgery, University of Athens, Greece, a tertiary referral centre. Subjects. Two hundred and ninety-three patients with a first episode of venographically or Doppler-proved DVT were included in the study, of whom 264 were followed up for 2 years. \textbackslash{} Interventions. After an initial extensive diagnostic workup, including routine blood counts and chemistries, erythrocyte sedimentation rate, CEA levels, chest X-ray and abdominopelvic CT scan, all patients were closely followed up and periodically examined. Main outcome measures. The incidence of cancer amongst patients with idiopathic and secondary DVT, and the validity of our screening programme. Results. Cancer was diagnosed in 21 out of 84 patients with idiopathic DVT (25\%) as compared with eight out of 202 patients with secondary DVT (4\%). In 22 out of the 29 cases, cancer was detected during the initial admission, and the remaining seven cases were detected during follow-up. Cancer was diagnosed in 15 asymptomatic, healthy individuals, but only in seven of them was the diagnosis made by CT scan. Conclusion. Occult cancer is fairly common in patients with idiopathic DVT, but the routine use of extensive diagnostic studies for its detection remains to be validated by further prospective studies.}

The expression of oestrogen receptor (ER) protein in invasive carcinoma of the breast and its clinical significance has been extensively evaluated, Little information is available regarding ER expression in ductal carcinoma in situ (DCIS), In this study, 46 formalin-fixed, paraffin-embedded tissue specimens of mammographically detected DCIS were evaluated immunohistochemically for the presence of ER using specific monoclonal antibodies against ER (ER-ICA Abbott Lab), The associations between ER expression and histological type, degree of differentiation and patient menopausal status were evaluated, Positive ER staining was present in 72% of cases, Non-comedo types of DCIS were more frequently ER-positive than comedocarcinoma, ER-positive tumours were inversely correlated with the presence of nuclear pleomorphism, The incidence of ER in pre-menopausal and post-menopausal women was similar, In conclusion, ER expression is present in a considerable percentage of DCIS, and ER-positivity is associated with the degree of differentiation and non-comedo carcinoma variants.