A randomised phase II study of OSI-7904L versus 5-fluorouracil (FU)/leucovorin (LV) as first-line treatment in patients with advanced biliary cancers.

The prognosis of advanced biliary tract carcinoma is poor with chemotherapy limited to a palliative role. This randomised study was designed to evaluate the effectiveness of a new liposomal thymidylate synthase inhibitor (TSI), OSI-7904L, in parallel with a modified de Gramont regimen of 5-FU/LV in patients with advanced biliary cancer. Patients with previously untreated advanced or metastatic carcinoma of the biliary tract were randomised to receive either OSI-7904L 12 mg/m2 intravenously every 21 days or a modified de Gramont schedule of 5-FU/LV (intravenous l-LV 200 mg/m2, bolus 5-FU 400 mg/m2 and a 46-h infusion of 5-FU 2,400 mg/m2) every 14 days. Twenty-two patients were randomised, 11 to each group. No patients responded in the OSI-7904L arm, while one patient achieved a partial response in the 5-FU/LV arm. The rates of disease stabilisation were 4/11 (OSI-7904L) and 10/11 (5-FU/LV). Both treatment arms were generally well tolerated. These results show that the activity of OSI-7904L is below a level of clinical relevance in advanced biliary tract cancer, providing only a small degree of disease stabilisation. A simplified de Gramont schedule appears to have marginally more activity. Both treatments were well tolerated.

Comparative evaluation of a new bedside faecal occult blood test in a prospective multicentre study.

BACKGROUND: Faecal occult blood testing is an established method of colorectal neoplasia screening. Guaiac-based tests are limited by poor patient compliance, low sensitivity, specificity and positive predictive value. Newer immunochemical-based tests, accurate but tedious, require a well-established laboratory set up. There is need for simpler immunochemical tests that can be performed at the out-patient clinic. AIM: To compare the performance characteristics of a new bedside immunological test strip device with a sensitive Guaiac-based and established immunochemical test for detection of faecal occult blood in patients undergoing colonoscopy. METHODS: A total of 389 consecutive patients from four centres who were referred for colonoscopy also provided the stool samples for detection of occult blood without dietary restrictions. Stool tests performed were (i) Guaiac-based, (ii) immunochemical enzyme-linked immunosorbent assay and (iii) bedside immunochemical strip test. RESULTS: At the optimal threshold level, the sensitivity and specificity of the beside immunochemical strip test for detection of significant colorectal neoplasia (adenomas >1.0 cm and carcinomas) were 60% and 95%, respectively. CONCLUSIONS: This bedside immunochemical strip test proved to be a simple, convenient, non-cumbersome and accurate tool with similar performance characteristics for detection of any bleeding lesion including colorectal neoplasia when compared with an established immunochemical faecal occult blood test.

Frequency of colorectal polyps in patients with sporadic adenomas or adenocarcinomas of the papilla of vater--an age-matched, controlled study.

BACKGROUND: Epithelial tumors of the papilla of Vater are rare neoplasms of the gastrointestinal tract. The carcinogenesis of these tumors seems to be fairly analogous to the genetic mechanisms which have been described for colorectal carcinoma. Patients with familial adenomatous polyposis bear a particularly increased risk for periampullary tumors. Data on whether the prevalence of colorectal tumors is increased in patients with sporadic ampullary neoplasms are scarce. METHODS: 26 consecutive patients (16 women, 10 men; median age 59 years) with sporadic adenomas (n = 19) or adenocarcinomas (n = 7) of the ampulla of Vater were retrospectively evaluated. The study patients were compared with 104 age-matched asymptomatic controls. All patients had undergone total colonoscopy. RESULTS: Neoplastic colorectal polyps were present in a similar proportion (23%) of patients of the study group compared with 26% in the control group (p > 0.05). Overall, 16 polyps were found among patients with ampullary tumors and 40 in asymptomatic controls (p > 0.05). Colonoscopy detected rectal carcinoma in 2 patients (8%) of the study group. Patients with and without colorectal polyps differed neither significantly by age nor by ampullary histological findings. 50% of the colonic polyps in patients with ampullary neoplasms were located in the ascending colon. CONCLUSIONS: The frequency of colorectal polyps in patients with ampullary tumors did not exceed the risk in the control group. However, the finding of 2 rectal carcinomas among patients with ampullary neoplasms supports the place of screening colonoscopy for the diagnostic work-up of ampullary tumors. Prospective multicenter studies should address this issue to provide a broad basis for future recommendations.

An infected esophageal duplication cyst in a patient with non-Hodgkin's lymphoma mimicking persistent disease.

Differentiation of mediastinal cysts appearing as soft-tissue attenuation masses on computed tomography (CT) scans from malignant mediastinal masses is difficult. We report a patient with non-Hodgkin's lymphoma, who was considered to have persistent disease in the posterior mediastinum based on CT scans. However, endoscopic ultrasound (EUS) demonstrated a paraesophageal, fluid-filled cyst with echodens inclusions and no evidence of any solid component. EUS-guided fine-needle aspiration (FNA) revealed mucous, epithelial and inflammatory cells, and additionally candida albicans was cultured. Based on these findings and constant size during follow-up, the diagnosis of an infected esophageal duplication cyst was made. Thus, this report further demonstrated the impact of EUS and EUS-FNA for management of posterior mediastinal cystic lesions in selected cases.

Long-term failure of endoscopic suturing in the treatment of gastroesophageal reflux: a prospective follow-up study.

BACKGROUND AND STUDY AIMS: Several endoscopic antireflux therapies have been marketed, but long-term data on their objective and clinical efficacy are sparse. This report presents prospective 1-year follow-up results, including technical, clinical, and functional success rates, for the first of these treatments to be developed, endoscopic gastroplication (EGP). PATIENTS AND METHODS: A total of 43 EGP procedures were carried out in 38 patients with gastroesophageal reflux disease (GERD). Two or three EndoCinch gastroplications were constructed at the level of the gastric cardia in each patient; five patients were treated twice within 6 - 12 months. Each endoscopic suture joined two gastric folds to each other as a double fold, known as a "gastroplication", in order to narrow the esophagogastric junction. Postprocedure data after 2 months and after 1 year were compared with preoperative data, focusing on symptoms, medication requirements, endoscopic findings, and pH-metry results. RESULTS: In contrast to the findings at 2 months (which showed that 72 % of the sutures were present and that there was a reduction in the percentage of time when the esophageal pH was < 4 from 15.4 % to 8.7 %), the results 1 year after EGP were considered to indicate failure of the treatment in all 38 patients because none of them still had all of the initially placed gastroplications in situ (90 % of gastroplications were lost). The percentage of patients who did not require proton pump inhibitor medication decreased from 52 % at 2 months to only 20 % at 1 year and even more patients had evidence of reflux esophagitis at 1 year (56 %) than had initially demonstrated signs of this (41 %). CONCLUSIONS: EGP has some short-term beneficial effects on clinical symptoms and pH-metry. However, mainly due to the loss of the endoscopically placed sutures, these effects were not maintained at the 1-year follow-up. EGP cannot therefore be recommended for routine clinical use. Better endoscopic methods need to be developed, and they should be adequately tested before being marketed.

Automated mass detection in contrast-enhanced CT colonography: an approach based on contrast and volume.

The purpose of this feasibility study was to design and test an algorithm for automating mass detection in contrast-enhanced CT colonography (CTC). Five patients with known colorectal masses underwent a pre-surgical contrast-enhanced (120 ml volume 1.6 g iodine/s injection rate, 60 s scan delay) CTC in high spatial resolution (16-slice CT: collimation: 16x0.75 mm, tablefeed: 24 mm/0.5 s, reconstruction increment: 0.5 mm). A CT-density- and volume-based algorithm searched for masses in the colonic wall, which was extracted before by segmenting and dilating the colonic air lumen and subtracting the inner air. A radiologist analyzed the detections and causes of false positives. All masses were detected, and false positives were easy to identify. Combining CT density with volume as a cut-off is a promising approach for automating mass detection that should be further refined and also tested in contrast-enhanced MR colonography. More information under http://www.screening.info.

Enteral nutrition by endoscopic means; I. Techniques, indications, types of enteral feed.

Enteral nutritional support plays a major role in the management of patients who are critically ill in intensive care units (ICU), those with poor volitional intake, persons with chronic neurological or mechanical dysphagia, and individuals with gut dysfunction. Part I of this review will briefly discuss the principles governing nasoenteral feeding and will describe in detail the endoscopic-assisted methods for placing enteral feeding tubes. These include percutaneous endoscopic gastrostomy, jejunal extension through a percutaneous endoscopic gastrostomy or direct endoscopic jejunostomy, and the "one-step button". In addition, the types of enteral food with focus on disease-specific enteral diets will be discussed. Finally, the latest innovations in enteral feeding including immune-enhancing nutrients such as arginine, omega-3 fatty acids, glutamine, and nucleotides advocated for critically ill patients will be discussed. Questions regarding possible complications and long-term results of the various methods of enteral feeding will be discussed separately in part II.

Enteral Nutrition by Endoscopic Means; II. Complications and Management.

Despite the benefits and the widespread use of enteral and tube feeding (ETF) some patients experience complications, which can be divided in three categories: mechanical, e. g., tube blockage or removal; gastrointestinal, e. g., vomiting, diarrhea; and metabolic, e. g., re-feeding syndrome, hyperglycemia. The type and frequency of complications related to tube feeding varies considerably in accordance with the access to the intestinal tract (e. g., nasoenteric vs. percutaneous gastric vs. small bowel), the composition of the formula diet used, and the severity of the underlying disease. For example, tube-related complications have been reported to occur in 0-20 % and gastrointestinal complications in 8-65 % of patients during early postoperative feeding via a needle catheter jejunostomy (NCJ) using comparable techniques. The complication rate can be reduced by careful observance of guidelines on tube feeding including those related to food composition, administration rate, portion size, food temperature, and supervision of the patient. Gastrointestinal side effects (including diarrhea) are without doubt the most frequent.

Phase- and size-adjusted CT cut-off for differentiating neoplastic lesions from normal colon in contrast-enhanced CT colonography.

A computed tomography (CT) cut-off for differentiating neoplastic lesions (polyps/carcinoma) from normal colon in contrast-enhanced CT colonography (CTC) relating to the contrast phase and lesion size is determined. CT values of 64 colonic lesions (27 polyps <10 mm, 13 polyps > or =10 mm, 24 carcinomas) were determined by region-of-interest (ROI) measurements in 38 patients who underwent contrast-enhanced CTC. In addition, the height (H) of the colonic lesions was measured in CT. CT values were also measured in the aorta (A), superior mesenteric vein (V) and colonic wall. The contrast phase was defined by xA + (1-x)V using x as a weighting factor for describing the different contrast phases ranging from the pure arterial phase (x=1) over the intermediate phases (x=0.9-0.1) to the pure venous phase (x=0). The CT values of the lesions were correlated with their height (H), the different phases (xA+(1-x)V) and the ratio [xA+(I-x)V]/H. The CT cut-off was linearly adjusted to the imaged contrast phase and height of the lesion by the line y=m[xA+(1-x)V]H+y(0). The slope m was determined by linear regression in the correlation (lesion approximately [xA+(i-x)V]/H) and the Y-intercept y(0) by the minimal shift of the line needed to maximize the accuracy of separating the colonic wall from the lesions. The CT value of the lesions correlated best with the intermediate phase: 0.4A + 0.6V (r=0.8 for polyps > or =10 mm, r=0.6 for carcinomas, r=0.4 for polyps <10 mm). The accuracy in the differentiation between lesions and normal colonic wall increased with the height implemented as divisor, reached 91% and was obtained by the dynamic cut-off described by the formula: cut-off (A,V,H)=1.1 [0.4A+0.6V]/H+69.8. The CT value of colonic polyps or carcinomas can be increased extrinsically by scanning in the phase in which 0.4A + 0.6V reaches its maximum. Differentiating lesions from normal colon based on CT values is possible in contrast-enhanced CTC and improves when the cut-off is adjusted (normalized) to the contrast phase and lesion size.

[Early detection of colorectal tumors: CT or MRI?]. / Früherkennung von kolorektalen Tumoren: CT oder MRT?

Cancer screening is currently offered for the organs breast, prostate, cervix and colorectum. With progressing technique in computerized tomography (CT) and magnetic resonance imaging (MRI) the colorectum can be increasingly better assessed. Because in CT and MRI also other organs are imaged with the colorectum, a colorectal screening automatically becomes a multiorgan screening. CT and MRI protocols designed for early detection of colorectal tumors are presented and discussed with regard to monoorganscreening (in CT: low dose, no i.v. contrast) and multiorganscreening (in CT: diagnostic dose for neighboured organs with i.v. contrast). More information under http://www.multiorganscreening.org.

Multidetector CT of the colon.

Multidetector technology, enabling faster imaging, higher spatial resolution and reduction in radiation dose, increases the role of CT in colonic diagnostic. The higher spatial resolution in the z-direction also changes the way to analyze the images. Instead of reading axial sections, now the colon can be systematically assessed in 3D by scrolling through multiplanar reconstructions or in CT colonography by virtual endoscopy. With ongoing improvements in computer-aided diagnosis CT colonography becomes an alternative to fiberoptic colonocopy for screening (http://www. multiorganscreening.org). In this article we propose a CT examination protocol for the colon, describe the typical imaging findings of different colonic diseases, and summarize the current status of CT colonography.

Phase I study of gemcitabine in combination with cisplatin, 5-fluorouracil and folinic acid in patients with advanced esophageal cancer.

The prognosis for advanced esophageal carcinoma is poor with a median survival of 9-12 months and 5-year-survival rate of 10-20%. Combination chemotherapy with cisplatin and 5-fluorouracil (5-FU) is considered to be the standard therapy, but has a high potential of side effects and is usually not given on an ambulatory basis. This phase I study was designed to find the maximum tolerated dose (MTD) of weekly cisplatin in combination with standard doses of gemcitabine (1,000 mg/m(2), 30 min) and 5-FU (750 mg/m(2), 24 h)/folinic acid (200 mg/m(2), 30 min). All drugs were to be given on a day 1, 8, 15 and 22 of a 6-weekly cycle in an outpatient setting. Nineteen chemonaive patients with inoperable stage IIa, III and IV squamous cell carcinoma and adenocarcinoma of the esophagus were enrolled into the study. Eight, six and five patients were enrolled at cisplatin dose levels 0 (20 mg/m(2) ), I (25 mg/m(2) ) and II (30 mg/m(2)), respectively. One hundred and eighty-one out of 187 treatments (55 cycles) were given on an outpatient basis. The dose-limiting toxicities of this schedule were leukopenia and thrombocytopenia. Other side effects were mild. Dose level II (30 mg/m(2)) was defined as the MTD for cisplatin when used in this combination and schedule. Partial responses were observed in 10 of the 19 enrolled patients. The side effect profile seen in this study in combination with the preliminary evidence of efficacy justifies further testing in a phase II setting with a cisplatin dose of 25 mg/m(2) and offers a treatment option for patients in an outpatient setting.

[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.

Preoperative staging of esophageal carcinoma: miniprobe sonography versus conventional endoscopic ultrasound in a prospective histopathologically verified study.

BACKGROUND AND STUDY AIMS: Endosonographic staging of esophageal carcinoma may be limited by non-traversable tumor stenoses. Dilation of malignant esophageal strictures carries a significant risk of esophageal perforation. We therefore evaluated the use of ultrasonic miniprobes in the staging of stenotic esophageal carcinoma compared with conventional endoscopic ultrasound. PATIENTS AND METHODS: In a blinded, prospective study, which included histopathological evaluation, 53 consecutive patients (43 male, 10 female, mean age 61 years) with stenosing esophageal carcinomas were examined preoperatively. Endosonography was done using the optical GF-UM3 echo endoscope. If tumor strictures were not traversable with this instrument, a blind esophagoprobe, the MH-908 was used for endosonography. Miniprobe sonography (MPS) was done during esophagoscopy in all patients. The various imaging modalities were assessed in terms of complete tumor traversability and correct tumor staging. Every patient underwent surgical tumor resection. RESULTS: MPS of the esophagus and proximal parts of the stomach was possible in all 53 patients without prior dilation of tumor stenoses. Endosonography with the GF-UM3 instrument was precluded in 23 patients (43.4%) while in 20 of the latter patients the MH 908 esophagoprobe could be passed through tumor stenoses. The overall accuracy rates for depth of tumor infiltration (T) staging were: 62% (31/50) for endosonography (GF-UM3 plus esophagoprobe) and 86.8% (46/53) for MPS. The accuracy rates for T staging in tumors traversable both with the GF-UM3 echo endoscope and with miniprobes were 56.7% (17/30) for GF-UM3 and 80% (24/30) for MPS. The accuracy rates for T staging in tumors traversable only with the MH-908 esophagoprobe and with miniprobes were 70% (14/20) for the MH-908 and 95% (19/20) for MPS. With regard to the presence or absence of peri-esophageal metastatic lymph nodes (N staging), the accuracy rates were 83% (25/30) for MPS and 70% (21/30) for the GF-UM3, and 80% (16/20) for MPS and 70% (14/20) for the MH-908. CONCLUSION: Compared with conventional endosonography using 7.5-MHz large diameter instruments, MPS enables: a) safe passage through high-grade malignant esophageal strictures, achieving b) higher accuracy rates for T staging, and c) similar rates for N staging. The use of MPS can also represent an improvement in the comfort and safety of patients. Moreover, miniprobe sonography is highly cost-effective compared with conventional endosonography. Thus, MPS appears to be a valuable addition to the armamentarium for staging esophageal carcinoma.

Polypoid tumors of the major duodenal papilla: preoperative staging with intraductal US, EUS, and CT--a prospective, histopathologically controlled study.

BACKGROUND: An adenoma-carcinoma sequence also applies to adenomas of the major duodenal papilla. Therefore accurate preoperative diagnosis and tumor staging are essential to select the appropriate patients for adequate treatment. In a prospective, histopathologically controlled study of tumors of the main duodenal papilla, the preoperative diagnostic value of ultrasound (US) catheter probes applied during endoscopic retrograde cholangiopancreatography (ERCP) was investigated. METHODS: Intraductal US was compared with conventional endoscopic ultrasonography (EUS) and computed tomography (CT). In 27 consecutive patients with benign polypoid tumors of the major duodenal papilla (n = 12) and carcinomas of the papilla (n = 15), respectively, the value of these imaging procedures in determining tumor visualization, tumor diagnosis and tumor staging according to the TNM classification was assessed. Every patient underwent surgical resection; histopathologic evaluation of resected specimens served as the reference standard. RESULTS: Intraductal US was significantly superior to EUS and CT in terms of tumor visualization (100% vs 59.3% vs 29.6%, respectively). Sensitivity and specificity rates for intraductal US and EUS were 100% versus 62.5% and 75% versus 50%, respectively. Overall accuracy rate in tumor diagnosis for intraductal US (88.9%; 24 of 27) was significantly (p = 0.05) superior to EUS (56.3%; 9 of 16). The latter did not depict 4 adenomas and 7 carcinomas. Neither intraductal US nor EUS is suitable for detection of distant metastases. CONCLUSION: Intraductal US appears to be the most effective imaging method in visualizing, diagnosing and staging tumors of the major duodenal papilla. Combining ERCP with catheter probe sonography offers a new diagnostic modality that has some potential advantages for local staging of small tumors of the main duodenal papilla. Consequently, minimally invasive techniques for resection of seemingly benign tumors of the papilla or, even more so, of small carcinomas should preferably be based on intraductal US.

[Preoperative staging of stenosing esophageal carcinoma--prospective comparison of mini-endosonography with conventional endosonography]. / Präoperatives Staging stenosierender Osophaguskarzinome--Prospektiver Vergleich der Mini-Sondensonographie mit der konventionellen Endosonographie.

Staging of esophageal malignancies can easily and safely be performed with ultrasonic miniprobes. Unlike large-diameter ultrasonic instruments, miniprobes may pass even high-grade malignant esophageal strictures without prior bouginage. Image quality and resolution of miniprobe sonography exceeds that of conventional endosonography, thus achieving higher accuracy rates for T staging, while those for N staging have found to be similar. As miniprobe sonography is able to improve patients' convenience and security and is highly cost effective compared to conventional endosonography, miniprobe sonography appears to be a valuable addition to the staging armamentarium in esophageal carcinoma.

[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.