Mark van Blankenstein

Survival and Prognostic Indicators in Hepatitis B Surface Antigen-Positive Cirrhosis of the Liver

To evaluate indications for new therapies such as liver transplantation and antiviral therapy, survival of histologically proven hepatitis B surface antigen (HBsAg)-positive cirrhosis of the liver was assessed in a cohort of 98 patients followed up for a mean of 4.3 years. The overall survival probability was 92% at 1 year, 79% at 3 years, and 71% at 5 years. Variables significantly associated with the duration of survival were age, serum aspartate aminotransferase levels, presence of esophageal varices, and all five components of the Child-Pugh index (bilirubin, albumin, coagulation factors, ascites, encephalopathy). Multivariate analysis showed that only age, bilirubin, and ascites were independently related to survival. Survival of patients with decompensated cirrhosis (determined by the presence of ascites, jaundice, encephalopathy, and/or a history of variceal bleeding) and those with compensated cirrhosis at 5 years was 14% and 84%, respectively. For patients with compensated liver cirrhosis, hepatitis B e antigen (HBeAg) positivity was also a prognostic factor with a 5-year survival of 72% for HBeAg-positive cirrhosis and 97% for HBeAg-negative cirrhosis; the risk of death was decreased by a factor of 2.2 when HBeAg seroconversion occurred during follow-up. It is concluded that liver transplantation should be considered for patients with decompensated HBsAg-positive liver cirrhosis and antiviral therapy for patients with HBeAg-positive compensated cirrhosis.

Abnormal pattern of cell proliferation in the entire colonic mucosa of patients with colon adenoma or cancer

Using autoradiography after 1 h of pulsed labeling with tritiated thymidine in endoscopic biopsy specimens from normal-appearing mucosa, cell proliferation was determined at six predetermined sites of the whole colon in patients with neoplastic disease of the large bowel and was compared with that of subjects without macroscopic colonic pathology. The labeling index (the percentage of cells incorporating [3H]thymidine) was 8.6 +/- 0.5 (mean +/- SEM) in 13 patients with colon carcinoma (p less than 0.001 vs. 16 control patients whose labeling index was 4.9 +/- 0.2) and 9.1 +/- 0.4 in 11 patients with a large adenoma in the colon (p less than 0.001 vs. controls). Twenty-one patients with one or more small adenomas (diameter less than 1 cm) had a moderately increased cell proliferation compared with controls (labeling index 6.2 +/- 0.3, p less than 0.02 vs. controls). In patients with neoplastic disease an enlargement of the proliferative compartment was found, whereas 6 patients with Crohns colitis had values for labeling index and a distribution of labeled cells along the crypt comparable to that of control subjects. An increased cell proliferation was found along the entire colon under each of the neoplastic conditions studied. These findings indicate that although neoplastic lesions develop in a limited area of the colon, the entire large bowel may be at risk for tumor growth.

Risk of malignant progression in patients with Barrett's oesophagus: a Dutch nationwide cohort study

Background Reported incidence rates of oesophageal adenocarcinoma (OAC) in Barretts oesophagus (BO) vary widely. As the effectiveness of BO surveillance is crucially dependent on this rate, its clarification is essential. Methods To estimate the rate of malignant progression in patients with BO, all patients with a first diagnosis of BO with no dysplasia (ND) or low-grade dysplasia (LGD) between 1991 and 2006 were identified in the Dutch nationwide registry of histopathology (PALGA). Follow-up data were evaluated up to November 2007. Results 42 207 patients with BO were included; 4132 (8%) of them had LGD. Re-evaluation endoscopies at least 6 months after initial diagnosis were performed in 16 365 patients (39%), who were significantly younger than those not re-examined (58±13 vs 63±16 years, p<0.001). These patients were followed-up for a total of 78 131 person-years, during which 666 (4%) high-grade dysplasia (HGD)/OACs occurred, affecting 4% of the surveillance patient population (mean age: 69±12 years, 76% male). After excluding HGD/OAC cases detected within 1 year after BO diagnosis (n=212, 32%), incidence rates per 1000 person-years were 4.3 (95% CI 3.4 to 5.5) for OAC and 5.8 (95% CI 4.6 to 7.0) for HGD/OAC combined. Risk factors for HGD/OAC were increased age (eg, >75 years HR 12; 95% CI 8.0 to 18), male sex (2.01; 1.68 to 2.60) and presence of LGD at baseline (1.91; 1.53 to 2.40). Conclusion In this largest reported cohort of unselected patients with BO, the annual risk of OAC was 0.4%. Male sex, older age and LGD at diagnosis are independent predictors of malignant progression, and should enable an improved risk assessment in BO.

Coated self-expanding metal stents versus latex prostheses for esophagogastric cancer with special reference to prior radiation and chemotherapy: a controlled, prospective study

BACKGROUND Self-expanding metal stents seem to be safer than conventional prostheses for palliation of malignant esophagogastric obstruction. However, recurrent dysphagia caused by tumor ingrowth in uncoated types remains a problem. In addition, prior radiation and/or chemotherapy may entail an increased risk of complications. METHODS Seventy-five patients with an esophagogastric carcinoma were randomly assigned to placement of a latex prosthesis under general anesthesia or a coated, self-expanding metal stent under sedation. At entry, patients were stratified for location of the tumor in the esophagus or cardia and for prior radiation and/or chemotherapy. RESULTS Technical success and improvement in dysphagia score were similar in both groups. Major complications were more frequent with latex prostheses (47%) than with metal stents (16%) (odds ratio 4.07: 95% CI [1.35, 12.50], p = 0.014). Recurrent dysphagia was not different between latex prostheses (26%) and metal stents (24%). Hospital stay was longer, on average, after placement of latex prostheses than metal stents (6.3 +/- 5.2 versus 4.3 +/- 2.3 days; p = 0.043). Only prior radiation and/or chemotherapy increased the risk of specific device-related complications with respect to the esophagus (12 of 28 [43%] versus 8 of 47 [17%]; odds ratio 3.66: 95% CI [1.24, 10.82], p = 0.029). CONCLUSIONS Coated, self-expanding metal stents are associated with fewer complications and shorter hospital stay as compared with latex prostheses, and prior radiation and/or chemotherapy increases the risk of device-related complications with respect to the esophagus.

Reduced expression of the cadherin–catenin complex in oesophageal adenocarcinoma correlates with poor prognosis

The E‐cadherin–catenin complex is important for cell–cell adhesion of epithelial cells. Impairment of one or more components of this complex is associated with poor differentiation and increased invasiveness of carcinomas. Oesophageal adenocarcinomas causes early metastases, progress rapidly, and consequently have a poor prognosis. By means of immunohistochemistry, the expression of E‐cadherin and alpha‐ and beta‐catenin was studied in 65 oesophageal adenocarcinomas and 15 lymph node metastases. Expression of these proteins was evaluated with respect to clinico‐pathological parameters and patient survival. Expression of the proteins was strongly correlated. In carcinomas, reduced expression of E‐cadherin, alpha‐catenin, and beta‐catenin was found in 74, 60, and 72 per cent, respectively. Expression of E‐cadherin and alpha‐catenin correlated significantly with stage and grade of the carcinomas, whereas expression of beta‐catenin correlated only with grade. Reduced expression of all three proteins correlated with shorter patient survival. In contrast to grade, E‐cadherin and beta‐catenin were significant prognosticators for survival, independent of disease stage. We conclude that in oesophageal adenocarcinomas, decreased expression of E‐cadherin, alpha‐catenin and beta‐catenin are related events. Furthermore, expression of at least E‐cadherin and beta‐catenin is significantly correlated with poor prognosis.

Age and sex distribution of the prevalence of Barrett's esophagus found in a primary referral endoscopy center

BACKGROUND:Both the demographics underlying the sex ratio in the prevalence of Barretts esophagus (BE) and the status of BE without intestinal metaplasia (IM) are unclear.AIMS:To establish the demographics of histologically proven BE, IM+ and IM−, over a 15-yr period from a primary referral, endoscopy unit.PATIENTS AND METHODS:For all BE patients aged 20–89 yr, identified between 1982 and 1996, IM+ or IM−, prevalences were calculated per 100 first endoscopies.RESULTS:A total of 492 cases of BE, 320 (248 IM+) in males, 175 (127 IM+) in females were identified in 21,899 first endoscopies (10,939 males, 10,960 females). Between ages 20 and 59 yr in males and 20–79 in females, IM+, IM− and all BE prevalences rose by ±7.36% for each additional year of age (P = 0.92) with, however, a 20-yr age shift between the sexes, resulting in a male:female OR 4.15 95% CI 2.99–5.77. A declining rate of increase in over 59 males resulted in an overall male:female OR 2.14, 95% CI 1.77–2.58. Over the age of 79 yr, BE prevalences/100 first endoscopies fell from a maximum of 5.1 in males and 3.65 in females to 3.38 and 2.53, respectively.CONCLUSION:The 4:1 sex ratio and 20-yr age shift between males and females in the prevalence of BE, both IM+ and IM−, found in younger age groups, was the main cause of the overall BE 2:1 sex ratio. The very similar demographics of IM− and IM+ BE suggest they may be two consecutive stages in the same metaplastic process.

Prior radiation and/or chemotherapy has no effect on the outcome of metal stent placement for oesophagogastric carcinoma.

Objective It is still unclear whether prior radiation and/or chemotherapy (RTCT) increases the risk of complications after the placement of self-expanding metal stents in patients with inoperable oesophagogastric carcinoma. We evaluated the influence of prior RTCT on the outcome of stent placement in a large group of patients. Methods From October 1994 to December 2000, 200 patients underwent placement of self-expanding metal stents for malignant dysphagia, and were followed prospectively. Forty-nine of these patients had received prior RTCT (chemotherapy n = 35, radiation therapy n = 8, or both n = 6). Results At 4 weeks after stenting, the dysphagia score had improved similarly in patients with or without prior RTCT, from a median of 3 to 0 (P < 0.001). The occurrence of major complications (bleeding, perforation, fistula formation, fever and severe pain) was not different between patients with or without prior RTCT (29% vs 21%; relative risk (RR) = 1.15 (95% CI 0.54–2.46; P = 0.72)), as was the occurrence of recurrent dysphagia due to tumour overgrowth, stent migration, or impaction of a food bolus (35% vs 27%; RR = 1.49 (95% CI 0.71–3.13; P = 0.29)). Median survival of both patient groups after stent placement was similar (110 vs 93 days; RR = 0.90 (95% CI 0.60–1.34; P = 0.60) for prior RTCT versus no prior treatment). Only minor complications (mainly mild retrosternal pain) occurred more frequently in patients with prior RTCT (41% vs 15%; RR = 2.12 (95% CI 1.06–4.25; P = 0.035)). Conclusions Both the incidence of life-threatening complications and survival after placement of self-expanding metal stents for oesophagogastric carcinoma are not affected by prior RTCT, but retrosternal pain occurs more frequently in patients who had previously undergone RTCT.

A new design metal stent (Flamingo stent) for palliation of malignant dysphagia: a prospective study ☆ ☆☆ ★

BACKGROUND Metal stents are not superior to conventional endoprostheses with respect to the incidence of recurrent dysphagia because of tumor ingrowth with uncovered stents and migration with their covered counterparts. To overcome these limitations, a partially covered (inside-out covering) metal stent with a conical shape and a varying braiding angle of the mesh along its length, the Flamingo stent, has been developed. METHODS From March 1997 to October 1997, 40 consecutive patients with dysphagia due to malignant tumors had either a small diameter (proximal/distal diameter 24/16 mm; n = 21) or a large diameter Flamingo stent (proximal/distal diameter 30/20 mm; n = 19) placed. RESULTS There was statistically significant improvement in dysphagia, but improvement was not greater with large diameter stents compared to small diameter stents (p = 0.21). Major complications (bleeding [4], perforation [1], fever [1] and fistula [1]) occurred in 7 (18%) patients. Large diameter stents tended to be associated with more major complications than small diameter stents (5 vs. 2; p = 0.07). Pain following stent placement was observed in 9 (22%) patients and occurred more frequently in those who had prior radiation and/or chemotherapy (p = 0.02). Recurrent dysphagia (mainly due to tumor overgrowth) occurred in 10 (25%) patients. CONCLUSIONS Flamingo stents are effective for palliation of malignant dysphagia, but the large diameter stent seems to be associated with more complications involving the esophagus than the small diameter stent. Because recurrent dysphagia is mainly due to tumor progression, further technical developments in stent design are needed.

Percutaneous metallic self-expandable endoprostheses in malignant hilar biliary obstruction

Forty-five patients with malignant hilar obstruction were treated with a total of 68 percutaneously inserted metallic self-expandable endoprostheses (Wallstents) for palliative biliary drainage. The stent diameter was 1 cm; the length was 3.5 to 10.5 cm. Early complications occurred in seven patients (16%), including cholangitis in four patients (9%). The 30-day mortality rate was 9%, with two procedure-related deaths (4%). Of the 45 patients, 29 died between 10 and 550 days (median, 126 days) after stent insertion. Reobstruction occurred in 13 of these patients after 26 to 184 days (median, 105 days). Sixteen patients were alive 44 to 737 days (median, 305 days) after stent insertion. Reobstruction occurred in four patients after 142 to 279 days (median, 246 days). The cause of reobstruction was proximal overgrowth in seven patients; distal overgrowth in four patients; and tumor ingrowth and proximal overgrowth, tumor ingrowth, hemobilia, and angling of the stent in one patient each. The cause of reobstruction was not established in two patients. Reintervention was performed in 14 patients (31%). Because reobstruction of Wallstent endoprostheses is primarily not stent-related but rather is caused by tumor progression, and because insertion and reintervention is easier, we consider the use of the Wallstent in malignant hilar biliary obstruction advantageous in comparison with plastic stents.

Barrett's oesophagus: epidemiology, cancer risk and implications for management

Although endoscopic surveillance of patients with Barretts oesophagus has been widely implemented, its effectiveness is debateable. The recently reported low annual oesophageal adenocarcinoma risk in population studies, the failure to identify most Barretts patients at risk of disease progression, the poor adherence to surveillance and biopsy protocols, and the significant risk of misclassification of dysplasia all tend to undermine the effectiveness of current management, in particular, endoscopic surveillance programmes, to prevent or improve the outcomes of patients with oesophageal adenocarcinoma. The ongoing increase in incidence of Barretts oesophagus and consequent growth of the surveillance population, together with the associated discomfort and costs of endoscopic surveillance, demand improved techniques for accurately determining individual risk of oesophageal adenocarcinoma. More accurate techniques are needed to run efficient surveillance programmes in the coming decades. In this review, we will discuss the current knowledge on the epidemiology of Barretts oesophagus, and the challenging epidemiological dilemmas that need to be addressed when assessing the current screening and surveillance strategies.