Radiotherapy combined with hyperthermia for primary malignant melanomas of the esophagus.

Primary malignant melanoma of the esophagus (PMME) forms about 0.1% of all primary esophageal cancers. Treatment options are very limited for patients unfit for surgery. This is the first report describing the results of external radiotherapy combined with regional hyperthermia for two inoperable PMME patients. Two patients with a T2-3N0M0 PMME were considered unfit for surgery based on age and general condition. External radiotherapy of a total dose of 35 Gy was given in a scheme of seven times 5 Gy, two times per week, and once weekly combined with external and intraluminal hyperthermia (aim 43°C). Toxicity was mild and both patients completed treatment according to protocol. Adequate temperatures at the intraluminal border of the tumor were achieved. In both patients, a complete remission was achieved with complete relief of obstructive symptoms and without signs of locoregional tumor progression until the end of follow-up at 11 and 15 months. External radiation combined with regional hyperthermia could be a good alternative to resection in patients unfit for surgery with a malignant melanoma of the esophagus.

The effect of oral administration of ursodeoxycholic acid and high-dose proton pump inhibitors on the histology of Barrett's esophagus.

Bile acids may play a role in the pathogenesis of Barrett's esophagus (BE). Bile composition can be influenced by oral administration of ursodeoxycholic acid (UDCA). We prospectively investigated the effect of proton pump inhibitors (PPI) supplemented with UDCA in vivo in patients with BE. Patients with no or low-grade dysplasia who were clinically asymptomatic on PPI were eligible for the study. In order to exclude the effects of acid reflux, all patients were initially treated with 40 mg esomeprazole (ESO) twice daily for 6 months and continued on this dose till the end of the study (t = 12 months). During a period of 6 months (t = 6 month - t = 12 month) patients were treated with oral UDCA (600 mg twice daily). Patients underwent endoscopy at t = 0 months, t = 6 months and t = 12 months with multiple biopsies of the distal and proximal BE segment, normal squamous and gastric cardia. In addition, pH was measured at t = 0 months and t = 6 months using a BRAVO wireless pH capsule. Bile was sampled at the beginning of the UDCA treatment and 6 months later (t = 6 month and t = 12 month). All biopsies were reviewed for the extent of metaplasia, dysplasia, and acute and chronic inflammation. In addition, proliferation (Ki67), differentiation (villin, cytokeratins 7 and 20) and inflammation (COX-2) were investigated by immunohistochemistry (IHC). Nine patients (mean age 60 years, median BE length 7 cm) were included, of whom six had no dysplasia and three had low-grade dysplasia. pH measurements revealed a normal acid exposure in most patients at t = 0 and t = 6 months. In addition, bile composition analysis demonstrated the efficacy of UDCA. Combining the results of both phases of the study, no significant changes were seen in any of the histological or IHC parameters. Differentiation and proliferation parameters showed no significant changes. In this study, in BE patients who were clinically asymptomatic on PPI, increasing the PPI dose to the maximum for 6 months followed by the addition of UDCA for 6 months did not result in significant histological or IHC changes in their BE.

Potential impact of EUS-FNA staging of proximal lymph nodes in patients with distal esophageal carcinoma.

BACKGROUND AND STUDY AIMS: Distal esophageal carcinomas can be resected using transthoracic esophagectomy or transhiatal esophagectomy. Accurate diagnosis of subcarinal and supracarinal lymph-node metastases is important for selecting the surgical strategy. The impact of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) on the preoperative diagnosis of subcarinal and supracarinal lymph-node metastases in patients with distal esophageal carcinoma was therefore investigated. PATIENTS AND METHODS: Patients with a resectable distal esophageal carcinoma and subcarinal and/or supracarinal lymph nodes visualized on preoperative EUS were prospectively included. The lymph nodes were sampled using EUS-FNA, and if they were found to have metastases, transthoracic resection was offered; by contrast, patients without metastases were offered a transhiatal resection. RESULTS: Lymph-node metastases were found with EUS-FNA in 11 of the 48 patients included (23 %). Thirteen patients had suspicious nodes on EUS, in four of whom (31 %) the diagnosis was changed into nonmalignant nodes with FNA. Thirty-five patients had nonsuspicious nodes on EUS, in three of whom (9 %) the FNA procedure revealed malignant cells. CONCLUSIONS: EUS with the addition of the FNA procedure has a significant impact on decision-making in patients with esophageal carcinoma in whom transhiatal esophagectomy would otherwise be planned.

Differences and similarities of adenocarcinomas of the esophagus and esophagogastric junction.

During the last few decades there has been an alarming rise in the incidence of tumors originating at the esophagogastric junction (EGJ) [1]. The reason for this is unknown. Tumors of the EGJ can be categorized in two types of cancer divided according to their anatomical origin: distal esophageal adenocarcinoma and adenocarcinoma of the gastric cardia. However, due to their location, in the transitional zone of the esophagus and stomach, there is constant debate about the proper classification, staging, and management of these tumors. The etiology of distal esophageal adenocarcinoma is clearly related to gastroesophageal reflux disease (GERD) and the development of a Barrett's esophagus [2]. The etiology of adenocarcinoma of the gastric cardia is less well understood. In the present paper, we will discuss the clinical characteristics and clinical management of esophagogastric tumors. Special attention will be given to differences and similarities of adenocarcinomas of the gastric cardia and distal esophagus.

Outcome of patients with esophageal carcinoma and suspicious celiac lymph nodes as determined by endoscopic ultrasonography.

BACKGROUND AND STUDY AIMS: The management of patients with esophageal cancer with malignant celiac lymph nodes (CLNs) is controversial. In this study we evaluated the management and survival of patients with positive CLN findings on endoscopic ultrasonography (EUS) and compared the outcome in surgically treated patients with that of nonsurgically treated patients. PATIENTS AND METHODS: The EUS database of the Academic Medical Center was retrospectively searched for patients with esophageal carcinoma and EUS-positive CLN. Follow-up comprised the review of medical charts and contact with general practitioners. RESULTS: From 1993 through 2000, 78 patients with esophageal carcinoma and suspicious CLN were eligible for inclusion in this study. The median survival of patients with CLN size < 2 cm was 13.5 months vs. 7.0 months for patients with CLN size >2 cm ( P = 0.01). In a multivariate model, CLN size was the only predictive factor for poor patient survival. Of the 78 study patients, 13 underwent a surgical resection and 65 received nonsurgical treatment. The surgical group was significantly younger and all patients in this group had CLN size < 2 cm. The median survival for the surgical group was 13.7 months vs. 13.5 months for the nonsurgical group with CLN size < 2 cm ( P = 0.63). CONCLUSIONS: In this retrospective study, CLN size was a significant predictor for poor survival. The surgically treated patients had a medium-term survival similar to that of nonsurgically treated patients with a CLN size < 2 cm. These findings underline the prognostic value of CLN size in patients with esophageal carcinoma.

[Barrett's esophagus: new developments in endoscopic surveillance]. / Barrett-slokdarm: nieuwe ontwikkelingen in endoscopische surveillance.

The current surveillance strategies for patients with a Barrett's oesophagus are hampered by the poor endoscopic visibility of early neoplastic lesions, the sampling error of random biopsies, the subjectivity of the histological evaluation, and the low incidence of carcinoma. New endoscopic techniques are available for a more reliable evaluation of a Barrett's oesophagus: high-resolution endoscopy, chromoendoscopy, fluorescence endoscopy and optical coherence tomography. The use of molecular markers will probably lead to a better risk stratification of patients. Detection of aneuploid cell populations and assessment of an increase of the number of cells in the S- and G2-phase are possible with DNA flow cytometry; flow cytometric abnormalities may be a more reliable predictor of carcinoma than histological assessment. A combined approach with the new endoscopic techniques and molecular markers may lead to a more efficient and cost-effective surveillance programme.

[Barrett's esophagus: endoscopic treatment of high-grade dysplasia and early cancer]. / Barrett-slokdarm: endoscopische behandeling van hooggradige dysplasie en vroegcarcinomen.

In a Barrett's oesophagus without dysplasia, endoscopic control every 3-5 years is sufficient. If low-grade dysplasia is encountered in the surveillance biopsies, then endoscopy should be repeated within 3-6 months and yearly thereafter if the low-grade dysplasia persists. Antacid medication must be prescribed in cases with extensive inflammation. The endoscopic treatment of patients with high-grade dysplasia and/or early cancer of the mucosa in a Barrett's oesophagus (tissue ablation and/or mucosa resection) seems a promising alternative to surgery in view of the combination of effectiveness, limited invasiveness compared to surgical resection, and the preservation of a functional oesophagus. Data from long-term follow-up are still limited. Strict endoscopic surveillance will probably detect metachronic abnormalities in an early and still curable stage, creating a new opportunity for endoscopic treatment.

Dysphagia caused by esophageal tuberculosis.

This report describes two patients with dysphagia who appeared to have esophageal tuberculosis. One patient had a fistula draining into a mediastinal mass. Both patients responded promptly to treatment with tuberculostatics. Surgery was not required. Esophageal tuberculosis is a rare entity.

Fulminant hepatitis B virus: recurrence after liver transplantation in two patients also infected with hepatitis delta virus.

Liver transplantation for hepatitis B virus (HBV)-related liver disease is complicated by HBV recurrence and, consequently, poor patient and graft survival. Patients transplanted for hepatitis delta virus (HDV)-related cirrhosis are reported to have a diminished incidence of HBV recurrence and improved graft survival. However, only a few reported HDV-infected patients had active HBV replicative disease before liver transplantation. In our experience, we transplanted two HDV-infected patients, both of whom had active HBV replication before liver transplantation. In one patient, hepatitis B surface antigen (HBsAg) recurred four months after transplantation. Two months later, Hepatitis Be antigen (HBeAg) and HBV-DNA became positive, and the patient died of fulminant recurrent hepatitis B and hepatitis delta. In the other patient, HBV persisted after transplantation, and 2 months later the patient required retransplantation for fulminant recurrent hepatitis B and hepatitis delta. With the second graft, the patient remained free of HBV infection for 1 year. Thereafter, the patient experienced HBV recurrence with active replication and died of fulminant hepatitis B and delta recurrence. In the first case and in the second graft of the second case, hepatitis B immunoglobulin (HBIG) immunoprophylaxis was administered in an attempt to prevent recurrence of HBV. The literature suggests that an HDV infection inhibits the replication of HBV and therefore plays a role in preventing the recurrence of HBV and improving survival. Our experience with two patients suggests that HDV infection, in the presence of active HBV replication, may not play a protective role.

Do cold agglutinins have any impact on the outcome of liver transplantation?

Cold agglutinins, IgM red blood cell autoantibodies, cause cold agglutinin disease with hemolysis and microvascular occlusion. Cold preservation of kidneys during renal transplantation in the presence of cold agglutinins can cause graft malfunction. However, the impact of cold agglutinins on the outcome of liver transplantation is unknown. We measured the pretransplant presence and titer of cold agglutinins in 327 primary liver allograft recipients and analyzed their relationship to outcome after transplant. Thirty-three percent of pretransplant patients had cold agglutinins. Cold agglutinins were more common in patients with viral-related liver diseases (49%) compared with those with nonviral-related liver disease (32%). There was no difference between recipients with and without cold agglutinins in usage of blood products, postoperative day 2 aminotransferase levels, acute rejection at day 7, the development of hepatic artery thrombosis, nonanastomotic biliary strictures, or 4-month allograft survival. In conclusion, cold agglutinins are common in liver transplant patients before surgery, especially those with viral-related liver diseases. However, the presence of cold agglutinins does not impact on outcome after liver transplantation.

Use of fatty donor liver is associated with diminished early patient and graft survival.

It is well known that implantation of donor livers with severe fatty infiltration (>60%) is frequently associated with early hepatic dysfunction and an increased incidence of primary nonfunction after liver transplantation. The outcome of donor livers with less fatty infiltration has not been well defined. We, therefore, studied the outcome of 59 liver transplantations in which donor livers with up to 30% fat were used. Patient outcome was compared to a time-matched control group of 57 patients. The two groups were similar in terms of age, gender, preservation time, primary diagnosis, and UNOS status. We compared both groups with regard to 4-month and 2-year patient and graft survival. We also assessed the incidence of ischemic type biliary strictures and hepatic artery thrombosis, and evaluated the causes of graft loss in both groups. We found that use of donor livers with up to 30% fatty infiltration was associated with a significant decrease in 4-month graft survival (76% vs. 89%, P<0.05) and in 2-year patient survival (77% vs. 91%, P<0.05). Primary nonfunction and primary dysfunction formed the main cause of graft loss and mortality. Multivariate analysis showed that fatty infiltration is an independent predictive factor for outcome after transplantation. We conclude that liver allografts with up to 30% fat lead to diminished outcome after liver transplantation. However, this diminished outcome should be viewed with respect to the increasing mortality on the national waiting list.