[Endoscopic ultrasound in the long-term follow-up of primary lymphomas of the stomach under conservative therapy]. / Endosonographie im Langzeitverlauf primärer Magenlymphome unter konservativem Therapieansatz.

BACKGROUND AND AIMS: The stomach is the main site of primary extranodular manifestation of non-Hodgkin's lymphomas. Besides clinical staging additional to histological diagnoses, the endoscopic ultrasound (EUS) also becomes more important during follow-up courses of conservative therapy regimens (e. g. H.p. eradication; radiochemotherapy). The aim of the present study was to assess the impact of EUS during long-term observation of primary gastric lymphomas and to outline possible changes of the gastric wall. PATIENTS AND METHODS: Within the scope of 2 prospective multicenter study on primary gastrointestinal non-Hodgkin's lymphomas (GIT-NHL), which were performed at Muenster University Hospital, 26 patients undergoing conservative treatment were examined with endoscopic ultrasound at a three-month interval between 01/1992 and 11/1998. The mean survey period was 28 months (range 7-62). RESULTS: In 22 patients over a period of 21 months (range 4-51) a histological proven complete remission (CR) was found. In 2 patients only a partial remission (PR) was achieved within a time period of seven respectively eight months of survey. Two other patients developed early relapse of non-Hodgkin's lymphoma. In patients with CR the endoscopic ultrasound showed a highly significant decrease of gastric wall thickness 7 and 12 months after therapy was started. On average after 4.6 months enlarged lymph nodes were no more detectable, after 5.5 months thickness of the gastric wall and finally after 6.6 month the previous abolished layering of the gastric wall returned to normal. CONCLUSION: In patients with gastric non-Hodgkin's lymphomas endoscopic ultrasound seems to be the only valid method which demonstrates early changes of the gastric wall and its layering in an appropriate way and might therefore in addition be capable to differentiate between CR, recurrent or refractory non-Hodgkin's lymphoma.

Cytology and image cytometry after colonic lavage: a complementary diagnostic tool in patients with ulcerative colitis.

BACKGROUND: Patients with extensive, long-standing ulcerative colitis have increased risk of colorectal cancer. AIMS: To improve the detection of high-risk patients, using a combination of colonic cytology, histology, and DNA image cytometry after segmental colonic lavage. PATIENTS: A series of 16 patients (8 high-risk patients) with ulcerative colitis were investigated. METHODS: After segmental lavage step, biopsies were obtained. Gradient centrifugation of the colonic fluid was performed for isolation and purification of epithelial cells. The smears and biopsy specimens obtained were stained for routine interpretation and for DNA image cytometry. RESULTS: Segmental lavage could be performed in all patients. Specimens from two high-risk patients showed low grade dysplasia and atypia by means of histology and cytology, respectively. In one patient, without increased colorectal cancer risk, atypia was detected. Three patients in the high-risk group, two of those diagnosed as positive for dysplasia and atypia, showed aneuploidy histologically and cytologically. DNA aneuploidy, in cytological material, was found exclusively in three low-risk patients, one of those had atypia cytologically. CONCLUSIONS: Isolation and purification of epithelial cells after segmental colonic lavage using density gradient centrifugation can be performed as part of routine endoscopy. It provides information about atypical cells and DNA aneuploidy as additional markers of malignant transformation. The combination of cytologic examination and DNA image cytometry might improve the detection of high-risk ulcerative colitis patients.

Fluorescence endoscopy using a fluorescein-labeled monoclonal antibody against carcinoembryonic antigen in patients with colorectal carcinoma and adenoma.

BACKGROUND AND STUDY AIMS: Various methods of fluorescence excitation and detection have been developed in gastrointestinal endoscopy. This study reports an endoscopic technique using locally applied fluorescein-labeled antibodies for in-vivo detection of colorectal dysplasia and carcinoma. PATIENTS AND METHODS: Fluorescence endoscopy with a fluorescein-labeled monoclonal antibody against carcinoembryonic antigen (CEA) was carried out in 27 patients with colonic polypoid lesions. During conventional colonoscopy, the monoclonal antibody was applied directly onto the mucosal surface. After an incubation time of 10 min, specific fluorescence was visualized with a conventional endoscope whose optical range was increased via two narrow-band filters. RESULTS: Fluorescence in vivo was present in 19 out of 25 carcinomas and in three of eight adenomas. The technique failed in the presence of mucosal ulceration or bleeding. One fluorescence-positive villous adenoma showed high-grade dysplasia, and another fluorescence-positive polypoid lesion was diagnosed as carcinoma in adenoma. Normal-appearing mucosa was fluorescence-negative in all cases. Endoscopic fluorescence significantly correlated with the CEA expression of luminal epithelial cells as determined immunohistochemically (Wilcoxon-Mann-Whitney U-test, P < 0.01). In all cases without ulceration or bleeding, the specificity of fluorescence endoscopy was 100%, the sensitivity was 78.6%, and the accuracy was 89.3%. CONCLUSIONS: Fluorescence endoscopy using fluorescein-labeled monoclonal antibody against CEA was shown to be positive in most cancers and some adenomas. Further and larger studies will be needed to demonstrate the value of this technique for differential diagnosis.

Diagnostic value of DNA image cytometry in ulcerative colitis.

The increased risk of colorectal cancer in patients with extensive, long-standing ulcerative colitis is well established. The interpretation of dysplasia as the common precursor lesion of colorectal cancer in ulcerative colitis is, however, subject to inter- and intraobserver variation. The histologic diagnosis is particularly difficult in the presence of acute inflammation. Therefore, the analysis of ploidy patterns might be a more objective diagnostic tool. In the present study, the correlation of ploidy and dysplasia of the colonic mucosa was evaluated in the absence and presence of inflammation. Image cytometry was performed on 561 fixed, paraffin-embedded tissue specimens from 67 patients with ulcerative colitis. Twenty patients had long-standing and extensive disease, including eight patients in whom the colitis was associated with colorectal cancer. Dysplasia was only found in patients with long-standing colitis or with colorectal cancer and was significantly more often diagnosed in the case of concomitant inflammation. On the other hand, aneuploid patterns were shown to occur independent of inflammatory activity. Aneuploidy was present in all colorectal carcinomas associated with ulcerative colitis and in 46.2% of specimens with dysplasia. Moreover, aneuploidy was detectable in four of 12 samples with low-grade dysplasia as well as in one case devoid of any dysplastic alteration. Ulcerative colitis patients with low-grade dysplasia plus aneuploidy probably represent a subgroup that might be at higher risk of developing colorectal cancer than patients with low-grade dysplasia alone. All in all, image cytometry analysis might be instrumental in identifying neoplastic lesions even in cases of increased inflammatory activity or regenerative change.

[Bougie endosonography in the preoperative diagnosis of stenosing esophageal carcinomas]. / Bougieendosonographie in der präoperativen Diagnostik stenosierender Osophaguskarzinome.

BACKGROUND AND OBJECTIVE: Nowadays ultrasonic endoscopy is accepted as the most accurate method in the preoperative TNM staging of oesophageal tumour. At the time a diagnosis of oesophageal is made, 25-62% of patients have marked oesophageal stricture due to an advanced stage of the tumour. As a result, it is often impossible to pass a conventional endoscope and the examination is incomplete or a dilator has to be introduced at high risk of perforation or other complications. An ultrasonic oesophagoprobe (Olympus MH 908) with a diameter of 7.9 mm, its tip acting as a dilator has been developed so that even in high-grade oesophageal stricture a complete and low-risk investigation can be undertaken. The value of this instrument has been compared prospectively with that of a standard ultrasonic endoscope in patients with oesophageal stricture due to carcinoma and in relation to the postoperative histology. PATIENTS AND METHODS: Between May 1996 and February 1997, 62 patients (55 men, 7 women; average age 55.8 [41-82] years) with suspected or histologically confirmed oesophageal carcinoma were examined with the standard ultrasonic endoscope and the new oesophagoprobe. The two independent results were related to the postoperative histology. RESULTS: It was possible to compare the endoscopic results with the postoperative histology in 47 patients. In 55.8% it was not possible to pass the stricture with the standard ultrasonic endoscope (SE) so that an accuracy of only 41% was obtained in the T stage and 56.4% in the N stage. But with the oesophagoprobe (OP) an accuracy of 74.5% in the T stage and of 63% in the N stage were achieved. The difference in the findings between the two instruments was highly significant (p < 0.001) in those patients in whom the SE could not be passed through the stricture. For the T stage the accuracy was 14.3% vs. 76.2% (SE vs. OP); in the N stage it was 38.1% and 57.2%, respectively. When both instruments could be passed the results were comparable. CONCLUSIONS: Examination with the ultrasonic oesophagoprobe is a reliable and accurate method free of complications for the preoperative assessment of oesophageal carcinoma with stricture.

Budd-Chiari syndrome in a patient with factor V Leiden--successful treatment by TIPSS placement followed by liver transplantation.

The causes of Budd-Chiari syndrome (BCS) comprise several diseases leading to thrombophilia. One of the most common thrombophilic disorders is resistance against activated protein C, caused by a single point mutation of the factor V gene. In December 1993, a 22-year-old patient was given a diagnosis of subacute BCS with occlusion of all major hepatic veins. Placement of a transjugular intrahepatic portosystemic stent shunt led to rapid disappearance of ascites and hepatic encephalopathy. During the following two years, recurrent partial occlusions of the shunt were treated by balloon angioplasty. The cause of the BCS still being unknown, in October 1996 we performed extensive laboratory investigations concerning states of thrombophilia and found moderately elevated IgG anticardiolipin antibodies (19.7 U/ml) and a resistance against activated protein C caused by heterozygosity for a point mutation of the factor V gene (1691G-->A; factor V Leiden). As a consequence, oral anticoagulation with coumarin was initiated. In October 1997, elective liver transplantation was performed which led to disappearance of APC resistance. Moreover, IgG anticardiolipin antibodies have been negative since then. If BCS is caused by APC resistance, liver transplantation not only treats the chronic liver disease but also cures the state of thrombophilia since factor V is mainly synthesized in the liver.

Density gradient centrifugation of colonic fluid after segmental lavage: a method of purification of exfoliative epithelial colonic cells for cytological interpretation and image cytometry in patients with long-standing ulcerative colitis.

OBJECTIVES: Patients with extensive, long-standing ulcerative colitis (UC) have an increased risk for developing colorectal cancer. In this study, we wanted to establish a method for retrieving cytological material after segmental colonic lavage for further cytopathological investigations and for performing DNA image cytometry. METHODS: Ten patients with long-standing and extensive ulcerative colitis and 10 patients without macroscopic abnormalities were investigated. After segmental colonic lavage during routine colonoscopy a three-layer (1.146, 1.075, and 1.046 g/ml, respectively) density gradient centrifugation of the retrieved colonic fluid was performed for isolation and purification of the epithelial cells. For identification of the epithelial cells flow cytometry with monoclonal antibody against cytokeratin and counterstaining with propidium iodine was performed. The smears obtained were stained for routine cytopathological interpretation and for DNA image cytometry. RESULTS: In eight of 10 UC patients and in nine of 10 control group patients adequate cytological material could be obtained. The band on top of the density gradient at 1.046 g/ml could be identified as the epithelial cells. Atypical cells were found in smears of three UC patients. In these patients and in one additional patient aneuploid stemlines could be detected. In smears of control group patients neither atypical cells nor aneuploidy were present. CONCLUSIONS: Isolation and purification of epithelial cells after segmental colonic lavage by using density gradient centrifugation was performed. This cytological material is adequate for cytopathological interpretation and for DNA image cytometry. Information about atypical cells and DNA aneuploidy as an additional marker of malignant transformation in UC patients was obtained. The combination of cytological examination and DNA image cytometry might improve the detection of UC patients with high risk for colorectal cancer.

Immunoscopy--a technique combining endoscopy and immunofluorescence for diagnosis of colorectal carcinoma.

BACKGROUND: Colorectal carcinoma is a common malignant disease with a high mortality rate. It arises most frequently in adenomas of the colorectum with different grades of dysplasia. Endoscopy and biopsy are among the most reliable diagnostic tools currently available. Diagnosis of malignancy at an early stage is sometimes difficult. This study reports on a new method, "immunoscopy", that combines endoscopy and immunofluorescent diagnostic procedures; it is the first reported use of locally applied fluorescein-labeled antibodies for detection of colorectal carcinomas. METHODS: A monoclonal antibody against carcinoembryonic antigen was fluorescein labeled. In phase I, formalin-fixed tissue samples, and in phase II, postoperative fresh tissue samples from tumorous and nontumorous areas of resected colorectal carcinomas were studied. After being incubated for 10 minutes, specific fluorescence was visualized with a conventional endoscope whose range was increased by means of two narrow band filters. RESULTS: Because of high levels of autofluorescence, evaluation of immunoscopic investigations using formalin fixed tissue (phase I) was not carried out. Immunoscopic investigation with postoperative fresh tissue samples could differentiate between tumorous and nontumorous areas (p < 0.001). Immunoscopic results were compared with data from immunohistochemical investigations with anti-carcinoembryonic antigen on the same tissue samples. CONCLUSIONS: Immunoscopy can differentiate between malignant and benign mucosal areas in fresh tissue samples. The high sensitivity of immunoscopy could potentially make it a useful diagnostic complement to routine endoscopy.

[Metal stents in the biliopancreatic duct system--assessment of current status]. / Metallstents im biliopankreatischen Gangsystem--Standortbestimmung.

By the end of the eighties mesh stents were implanted in malignant stenoses of the biliary and pancreatic ducts for the first time. In the following years, self-expanding as well as balloon-expandable mesh stents were increasingly implanted in malignant stenoses by radiologists or interventional gastroenterologists, either percutaneously or endoscopically retrograde. In randomized comparative studies different teams showed relevant advantages of this new type of prosthesis in comparison to the commonly used plastic stents. Especially the significantly lower rate of late complications and longer patency rates speak in favor of the mesh stents. The higher cost of the mesh stent makes it important to carefully select patients before implantation, to let patients with potentially longer survival time profit from the advantages of the procedure. Expandable mesh stents were successfully implanted in benign stenoses of the biliopancreatic ducts as well, although the lack of randomized comparative studies makes a final assessment difficult. Concluding from already presented results, there might be a new therapeutical option for selected patients with benign stenoses of the biliopancreatic ducts.

Oral budesonide therapy for steroid-dependent ulcerative colitis: a pilot trial.

BACKGROUND: Budesonide, a corticosteroid with high topical anti-inflammatory activity and low systemic activity, has been shown to prolong time to relapse in Crohn's disease. In the present study, the efficacy of budesonide in an oral pH-modified-release formulation was evaluated for maintenance treatment in patients with steroid-dependent ulcerative colitis. METHODS: Fourteen patients with steroid-dependent ulcerative colitis in the reduction phase of conventional glucocorticosteroids (c-GCS) following a severe attack, were treated with budesonide 3 mg t.d.s. for 6 months. The primary investigation parameters were changes in the clinical activity index (CAI) and in the daily dose of c-GCS. RESULTS: In 11 cases the CAI improved significantly and treatment with c-GCS could be terminated. Three patients experienced relapse and needed further c-GCS treatment. The average daily dose of c-GCS and the average value of the CAI before treatment with budesonide were significantly higher in the relapse group than in the remission group. CONCLUSIONS: In patients with c-GCS-dependent ulcerative colitis, a dose of 9 mg budesonide daily in an oral pH-modified-release formulation was well tolerated, significantly decreased the CAI, and rendered c-GCS unnecessary in the majority of cases.

A controlled trial of intravenous immune globulin for the prevention of serious infections in adults with advanced human immunodeficiency virus infection.

BACKGROUND: Studies on human immunodeficiency virus-infected children suggest that high-dose immune globulin therapy might be beneficial in reducing the episodes of recurrent infections. In adults, comparable studies are not available. OBJECTIVE: To determine the efficacy of intravenous (IV) immune globulin therapy in preventing infections and reducing days with fever, as well as the duration and frequency of hospitalization for human immunodeficiency virus-infected adults, in a prospective, randomized outpatient clinical trial. METHODS: Adult patients who met Centers for Disease Control and Prevention criteria B and C were randomized to be treated with (n = 70) or without (n = 57) IV immune globulin. Patients who were assigned to treatment with IV immune globulin received 400 and 200 mg/kg of this drug initially and every 21 days thereafter, respectively. Primary end points were the occurrence of laboratory-proved or clinically diagnosed infections and death caused by infection. RESULTS: In comparison with patients in the control group, IV immune globulin treatment significantly increased the time for which the patients who met Centers for Disease Control and Prevention criteria B and C were free from serious infection (P < .001). Twelve (17%) of the patients who received IV immune globulin had infection-related deaths compared with 20 (35%) of the control patients; however, this was not statistically significant (P = .06). Furthermore, immune globulin treatment was associated with an overall reduction in the number and duration of hospitalizations for short-term care (P = .002), days with fever (P < .001), and frequency of diarrhea (P < .001). Because of these results, the study was stopped by the local ethical board. CONCLUSION: Prophylactic IV immune globulin treatment in human immunodeficiency virus-infected adults decreases the frequency of serious infections and is associated with a reduction of hospitalization for short-term care.

[Mini-probe ultrasound of the upper gastrointestinal tract--1995 state of the art and perspectives. Workshop on Mini-Probe Ultrasound in Gastroenterology, Münster, 28 October 1995]. / Minisonden-Sonographie im oberen Gastrointestinaltrakt-State of the Art 1995 und Perspektiven. Workshop zur Minisonden-Sonographie in der Gastroenterologie Münster, 28.10.1995.

Endoscopic ultrasound (EUS) allows for intraluminal sonographic imaging of the oesophagus, stomach, pancreatobiliary duct system, the papilla of Vater, as well as the colon and rectum. EUS has proved valuable for diagnosis and staging of tumours of the upper intestinal tract. EUS can also provide valuable additional information concerning lesions that cannot be immediately classified. As doing this involves, first, removal of the conventional endoscope and, second, insertion of the echo endoscope, EUS is not suitable for routine examinations. Therefore EUS has remained an independent endoscopic diagnostic modality. Moreover, due to their diameter conventional echoendoscopes cannot be inserted into the pancreatobiliary duct system. Fine calibre high frequency ultrasound probes promise a resolution of less than 2 mm in diameter. The following report is a summary of a one-day workshop which took place in Muenster, Germany on Oct. 28, 1995. Its goal was to define the current state of the art of miniaturised endoscopic ultrasound probes in the field of gastroenterology. During this workshop, possible clinical applications for diagnosis, therapy, as well as follow-up were described and discussed. The potential of miniaturised endoscopic ultrasound probes was explored in terms of possible future technical developments.

Adenoma of the papilla of Vater: a possible role for intraductal ultrasound (IDUS).

Like in adenomas of the colon, an adenoma-carcinoma sequence is expected from adenomatous growths in the papilla of Vater. Papilloadenomas must therefore be resected. Imaging techniques have a decisive influence on the choice of operative technique and consequently on perioperative mortality. Using conventional endoscopic ultrasonography, detection of lesions smaller than 10 mm in diameter is rare. The probes available up to now for intraductal sonography with an external diameter of between 3.4 and 12 mm were too rigid and could be inserted transpapillarily in only a few cases. The recent development, however, of high-frequency, extremely flexible ultrasound catheters with an external diameter of 1.17 mm makes intraductal examination of the pancreatic ductal system possible. We present a case of a 66 year-old female patient, in whom, for the first time, a histologically adenomatous lesion of the papilla of Vater could be examined with intraductal sonography using the endoscopic retrograde, transpapillary approach. As there was no evidence of infiltrative growth, the patient underwent a modified duodenum-preserving resection of the pancreatic head. Histological examination of the resected specimen confirmed the preoperative intraductal sonography findings. Since conventional endosonography did not detect the lesion in this case, intraductal sonography with flexible, high-frequency catheters as presented here, clearly may have a role in extending the possibilities of preoperative examination, especially of focal lesions in the periampullary region.

Arterio-biliary fistula after transjugular intrahepatic portosystemic shunt: a life-threatening complication of the new technique for therapy of portal hypertension.

We report on a 70-year old woman with chronic active hepatitis and portal gastropathy who was treated with TIPS. On day 28 after TIPS implantation hemobilia occurred and radiological examination of the abdomen showed migration and kinking of the portal stent. During an emergency intervention the dislocated stent was splinted with a further stent. The suspected portobiliary fistula, however, could not be detected. The subsequent angiography of the hepatic artery showed an arteriobiliary fistula in the area of the dislocated stent. By means of microparticles and coils this fistula could be occluded angiographically; the bleeding stopped completely. Three days after the successful occlusion of the arterio-biliary fistula the patient died of disseminated intravascular coagulation. We therefore recommend in case of hemobilia after TIPS placement an immediate evaluation of the bleeding to exclude an arterio-biliary communication. In order to avoid stent dislocation it is advisable not to use combination of stents with a different design (e.g., Wall-stent and Palmaz-stent).

Long-term experience in Wallstent therapy for malignant choledochal stenosis.

During a four-year period up to May 1993, 118 patients (mean age 69 years) with malignant bile duct stenoses were treated with a total of 127 selfexpanding 10-mm metal endoprostheses (Wallstent), most of them endoscopically (n = 102). Technical problems during and shortly after implantation occurred in five cases (4.2%), but could all be solved endoscopically. Serum bilirubin decreased from a mean of 8.0 mg/dl at presentation to a mean of 2.0 mg/dl after stenting. Nineteen patients died within the first three months (5% within the first 30 days); recurrent obstruction, as manifested by recurrent jaundice or cholangitis, or both, was encountered in 14%. Fifty-one patients who survived longer were followed up until death or for a minimum of 12 months (mean follow-up: 12 months). Stent patency rates in this group were 86% (six months), 72% (12 months) and 64% (18 months), survival for these time periods being 63%, 35% and 17%, respectively. No significant stent-related complications were noted; stent occlusion occurred in 12% of patients after a mean of 168 days, and was successfully managed endoscopically (thermal cleaning, implantation of further stents) in all cases. We conclude from our long-term follow-up data that patients surviving longer than three months are the ones most likely to benefit from Wallstent insertion for malignant jaundice.

[Structured documentation in gastroscopy: a method for improved quality assurance?]. / Strukturierte Gastroskopie-Befundung: Ein Weg zur verbesserten Qualitätssicherung?

To further improve quality assurance of gastrointestinal endoscopy, a computer assisted documentation system for gastroscopic data was assessed. In this context, for the structured written recording system, parameters "expenditure of time" and "acceptance by doctors" was evaluated. Contrary to free, unstructured data recording, the structured system employing predefined terms was able to promote doctors' acceptance of endoscopic terminology standards.

[Intraductal ultrasound of the pancreas--a procedure with diagnostic prospects? Initial preclinical experiences]. / Intraduktale Sonographie (IDUS) des Pankreas--Ein Verfahren mit diagnostischer Perspektive? Erste präklinische Erfahrungen.

For the first time, human pancreas specimens (18 autopsy specimens, three resection specimens) were examined with high-resolution, flexible ultrasound catheters (20 MHz; 3.5 F, 4.8 F, 5.0 F and 6.0 F external diameters; mechanical and electronic systems). The ultrasound catheter was easily inserted into the pancreatic duct in all specimens. The sonographic tissue texture was correlated with its histological picture at defined positions. A high resolution was thus achieved in the sonomorphological differentiation of blood vessels, duct system elements, fibrotic tissue, fatty tissue and pancreas tissue with varying lipomatous composition. In a radius of an average of 5.5 mm, structures 0.1 mm large were recognised. Contrast media studies of the ductal system were carried out before and after ultrasound examination. No evidence of trauma due to catheterisation was found either with these studies or by histology. In one case, a 15 mm serous microcystic adenoma of the pancreatic head was found at intraductal examination of the resection specimen. Clinical examinations within the framework of endoscopic retrograde pancreaticography must clarify if the intraductal ultrasonography technique presented here can truly enlarge the diagnostic, repertoire used in the search of tiny focal pancreatic lesions.