Mark G. Cowling

Internal Stenting in Malignant Biliary Obstruction

Internal stenting in inoperable malignant biliary obstruction plays an important role in patient management. Surgical bypass may still be undertaken where there is also duodenal obstruction, though the need for gastroenterostomy may be reduced with the increasing use of metallic stents for the relief of malignant gastric outlet obstruction. Stents may be placed endoscopically or percutaneously, though in most centers the endoscopic route is usually tried first, with the percutaneous route being reserved for endoscopic failures. Plastic and self-expanding metallic biliary stents are available, each with its own advantages and disadvantages. In general, longer periods of patency are observed with metallic stents, though they are more expensive. Plastic stents can be changed endoscopically relatively easily when they have blocked, and in practice it is common for plastic stents to be inserted via this route for initial biliary drainage. If there is prolonged survival thereafter, many workers insert a metallic stent in an attempt to reduce the number of interventions required. If the percutaneous route is being employed, the histologic diagnosis has been confirmed, and the malignancy is inoperable, our practice is to use a self-expanding metallic stent, as the delivery system is relatively small and subsequent occlusion less likely. Surgical treatment for malignant biliary obstruction is generally reserved for patients with potentially curable lesions, although palliative surgical bypass may be used in those with combined biliary and duodenal obstruction. Use of internal stents, inserted endoscopically or percutaneously, is firmly established for palliation of inoperable malignant obstructive jaundice. Endoprostheses are preferable to external catheters, as the latter are inconvenient for the patient, may be associated with pain and bile leakage around the catheter, may act as an entry point for infection, and serve as a constant reminder of the patient’s incurable disease. Traditionally, plastic stents have been used; but during the last 10 years or so metallic endoprostheses have been increasingly employed. They offer certain advantages over plastic stents, as is discussed below. Percutaneous Drainage In most centers endoscopic retrograde cholangiopancreatography (ERCP) has largely replaced percutaneous transhepatic cholangiography (PTC) for diagnostic purposes, and endoscopic stenting is the first line of therapy. The percutaneous approach is usually employed when the endoscopic approach has either failed or is not possible, as in patients with a history of partial gastrectomy or gastric outlet obstruction. Patients with hilar strictures are best treated percutaneously, as endoscopic drainage has higher failure and complication rates in this situation. Prior to stent insertion, computed tomography (CT) or ultrasound examinations are performed to assess the anatomy and plan the most appropriate approach for intervention. Any coagulopathy should be corrected with vitamin K administration, platelet transfusion, or both as appropriate. Adequate hydration should be ensured to minimize the risk of the hepatorenal syndrome. In view of the high incidence of bacterial colonization of the obstructed biliary tree [1], broad-spectrum antibiotics are administered intravenously prior to the procedure to minimize the incidence of cholangitis. In most cases we perform an initial PTC from the right side. A 22-gauge Chiba needle is used to opacify the duct system with contrast medium, and a suitable bile duct is chosen as the point of access for intervention. The most peripheral puncture possible should be made into the bile duct that provides the most direct line to the stricture to be stented. The peripheral puncture ensures that there is sufficient space above the stricture available for the stent (particularly important for hilar strictures), and the direct line ensures that stent insertion is as technically straightforward as possible. Having punctured a suitable duct with a 21-gauge needle, an 0.018-inch mandril guidewire is advanced through the needle into the biliary tree, and the needle is exchanged for a 4.5F dilator (Accustik; Boston Scientific, Watertown, MA, USA). This allows insertion of a conventional 0.035-inch guidewire, which can be used in combination with a biliary manipulation catheter to cross the stricture. Hydrophilic guidewires are useful in difficult cases. Occasionally it is not possible to cross a biliary stricture at the time of initial intervention, in which case it is necessary to leave an external biliary drain in situ for 24 to 48 hours to decompress the biliary tree. This reduces the amount of space around the catheter and makes it easier to direct it through the stricture. This approach is preferable to prolonged manipulation at the time of the first procedure, which can induce cholangitis. The ducts in the left lobe of the liver can be punctured with precision using ultrasound guidance. (We do not employ this approach routinely, as it delivers a higher radiation dose to the Correspondence to: M.G. Cowling, M.B.B.S. operator’s hands than the conventional right-sided approach.) Left duct puncture is preferable in patients with ascites, as there is more fluid present between the right lobe and the abdominal wall than anterior to the left lobe. Plastic Biliary Stents A large number of plastic biliary endoprostheses are available, each with relative advantages and disadvantages for combating the two main complications associated with their use: occlusion and migration. In general, occlusion due to bile encrustation is less frequent in plastic stents with a large internal diameter. However, large stents require large transhepatic tracks for their introduction, with a concomitantly increased incidence of pain and hemobilia. This can be prevented in part by leaving an internal/external drain across the stricture for 2 to 4 days, allowing the track to mature. In addition, large-caliber stents tend to be stiff and may buckle the guidewire at points of angulation, leading to bile duct perforation. To date, no randomized study has shown any benefit for using stents larger than 10F in diameter. The size of the endoscopic plastic stents is limited by the size of the instrument channel, currently a maximum of 12F; in our institution 10F stents are used most commonly. Other factors influencing the rate of stent occlusion include the stent material and the presence of side holes. There are conflicting data in the literature concerning stent materials. In experimental studies Teflon stents have been shown to be more prone to bile encrustation than stents made from other materials such as polyurethane or polyethylene [2]. More recently a study examining the use of a straight Teflon stent without side holes (Tannenbaum stent) demonstrated a median patency of 448 days [3]. Other work has indicated that the presence of side holes does not provide better drainage [4] and increases the occlusion rate. Most of those working in this field consider it best to use a stent with end holes only, except in hilar strictures, where the presence of side holes may assist in providing drainage of side branches of the duct containing the stent. As bile encrustation is due at least in part to bacterial action, it has been suggested that plastic stents should be deployed with their distal ends above the ampulla of Vater in patients with strictures that do not extend to the lower end of the common bile duct to minimize the occurrence of bacterial colonization and to reduce the risk of the stent becoming clogged by food material. This has the important practical disadvantage that occluded stents cannot easily be removed endoscopically and must be replaced by the more demanding percutaneous route. Studies performed on the value of antibiotics for preventing stent occlusion have reported inconsistent findings [5, 6]. Migration rates of plastic endoprostheses of 4% to 8% [7, 8] are commonly reported, but rates of up to 40% have been described [9]. Migration-resistant designs have been developed, such as double-mushroom stents [10] and spirals [11]. Another approach, used in the Carey-Coons endoprosthesis, is to attach the stent to a subcutaneous plastic button with a suture [8]. However, the button may cause pain, serves as a focus for infection, and may predispose to tumor seeding; because of these disadvantages most interventional radiologists discard the button before using CareyCoons stents. Metallic Stents There are two main types of metallic stent: balloon-expandable and self-expanding. In the biliary tree balloon-expandable stents are used infrequently because their relative rigidity is a significant disadvantage, especially when they must be deployed along a curve, as is frequently necessary in patients with hilar strictures. The main advantage of metallic stents is that they are introduced in a contracted state on a delivery system measuring approximately 8F in diameter. Thus they can be deployed through a small track but expand to a diameter of 8 to 10 mm, which is three times greater than that of plastic stents in common use. The initial steps of the insertion are identical to those for insertion of plastic stents. Once the stricture is crossed it is predilated with an 8to 10-mm angioplasty balloon. This allows for easier passage of the stent and its delivery system through the stricture, facilitates positioning, and generally allows the stent to expand sufficiently to provide adequate biliary drainage immediately after insertion. Dilatation of the stent after deployment is rarely necessary and carries the risk of displacing the endoprosthesis. Some workers choose not to predilate the stricture, but if the stent expands inadequately after deployment there is the risk of bile leakage into the peritoneum. The proximal end of metallic stents should be placed in a peripheral intrahepatic duct. This produces a stable position and

The role of transradial diagnostic angiography

PurposeTo evaluate the use of 4 Fr radial artery catheters as an alternative to both transbrachial and transfemoral approaches.MethodsSeventy examinations were performed via the transradial route using 4 Fr 130-cm-long pigtail catheters. Prior to puncture the radial artery was assessed with pulse oximetry to ensure that it did not contribute the dominant blood supply to the hand. Patients were reassessed for complications within 24 hr of the procedure.ResultsAcceptable images were obtained in femoral arteriography, arch aortography, and selective carotid studies. In three of six renal arteriograms, images were suboptimal. There was a total technical failure rate of 5.7%. Significant complications were encountered in 4.3%, but no hand ischemia occurred.ConclusionThe transradial route for arteriography is easy to learn and has a low complication rate. It is a reasonable alternative approach to transfemoral arteri-ography for true outpatient peripheral angiography and in cases where the transfemoral route is not feasible, though it did not prove satisfactory for renal arteriography in hypertensive patients.

Multislice CT Angiography in Renal Artery Stent Evaluation: Prospective Comparison with Intra-Arterial Digital Subtraction Angiography

AbstractPurpose: To assess the role of multislice computed tomography angiography (MCTA) in the evaluation of renal artery stents, using intra-arterial digital subtraction angiography (DSA) as the gold standard. Methods: Twenty consecutive patients (15 men, 5 women) with 23 renal artery stents prospectively underwent both MCTA and DSA. Axial images, multiplanar reconstructions and maximum intensity projection images were used for diagnosis. The MCTA and DSA images were each interpreted without reference to the result of the other investigation. Results: The three cases of restenosis on DSA were detected correctly by MCTA; in 19 cases where MCTA showed a fully patent stent, the DSA was also negative. Sensitivity and negative predictive value (NPV) of MCTA were therefore 100%. In four cases, MCTA showed apparently minimal disease which was not shown on DSA. These cases are taken as false positive giving a specificity of 80% and a positive predictive value of 43%. Conclusion: The high sensitivity and NPV suggest MCTA may be useful as a noninvasive screen for renal artery stent restenosis. MCTA detected mild disease in a few patients which was not confirmed on angiography.

Relationship of Matrix Metalloproteinases and Macrophages to Embolization during Endoluminal Carotid Interventions

Purpose: To investigate if relationships exist among macrophage infiltration, plasma matrix metalloproteinase (MMP) levels, and the number of emboli generated during endoluminal carotid interventions. Methods: Carotid endarterectomy specimens excised as intact cylinders (n=27) were subjected to a standardized angioplasty procedure under radiological guidance in an ex vivo pulsatile flow model. Emboli collected in distal filters were counted and sized using microscopy. Preoperative plasma gelatinase activity was determined by gelatin zymography and quantified using image analysis software. Levels of tissue inhibitors of metalloproteinases (TIMP) 1 and 2 were determined by ELISA. Macrophages within postangioplasty plaques were analyzed using immunohistochemical staining for CD68 antigen and graded by a blinded examiner. Statistical analysis was performed using Spearmans rank correlation. Results: The median number of emboli recorded during angioplasty was 104 (interquartile range 33.75–242.5, absolute range 13–1090). Plasma MMP-9 and MMP-2 levels correlated with emboli number (r=0.544 [p=0.003] and r=0.412, [p=0.033], respectively), while TIMP-1 and TIMP-2 levels did not. Macrophage infiltration within the plaques correlated with emboli number (r=0.722, p<0.001) and the plasma MMP-9 level (r=0.489, p=0.010). Conclusions: These data indicate that plaque macrophage infiltration may play a role in the generation of emboli during endoluminal carotid intervention, possibly via modulation of protease activity.

The potential role of optical coherence tomography in the evaluation of vulnerable carotid atheromatous plaques: a pilot study.

PurposeThe decision to intervene surgically in patients with carotid artery disease is based on the presence of symptoms, along with the severity of carotid artery stenosis as assessed by ultrasound or X-ray computed tomography (CT). Optical coherence tomography (OCT) is a relatively new imaging technique that offers potential in the identification of, as well as the distinction between, stable and unstable atherosclerotic plaques. The purpose of our study was to evaluate whether OCT can be used as a noninvasive diagnostic tool to reveal the morphology of carotid stenosis from the adventitial surface of the carotid artery. To achieve this aim, excised atheromatous plaques were scanned by OCT from the external surface.MethodsPlaques removed at carotid endarterectomy were scanned by OCT from the external surface within 72 hr of surgery and then examined histologically. The images of the histologic slides and the scans were then compared.ResultsWe examined 10 carotid endarterectomy specimens and were able to identify calcification, cholesterol crystal clefts, and lipid deposits in the OCT images with histologic correlation. The strong light scattering from the calcified tissue and cholesterol crystal clefts limited the depth of light penetration, making observation of the intimal surface and the detail of the fibrous cap difficult. However, we were able to confidently identify the absence of an atherosclerotic plaque by OCT scans even from the external surface.ConclusionThe results of this pilot study demonstrate that OCT can reveal the main features of carotid stenosis but that plaque vulnerability cannot be reliably and precisely assessed if scanned from the external surface with OCT in its present form.

Renal Artery Embolization - A First Line Treatment Option For End-Stage Hydronephrosis

Conventionally poorly functioning hydronephrotic kidneys have been removed if they are symptomatic. In our unit, patients are offered renal artery embolization as an alternative treatment option. Patients and Methods: Fifteen patients (11 male, 4 female) with a mean age of 32.9 yr (20–51 yrs) have undergone renal artery embolization for symptomatic hydronephrosis with poor function. Mean follow-up was 64.13 weeks (range 14–200). All patients had loin pain and hydronephrosis. Twelve patients had primary pelvi-ureteric junction obstruction (PUJO). Two patients had poorly functioning hydronephrotic kidneys secondary to chronic calculous obstruction. One patient had chronic pain in an obstructed but reasonably functioning kidney following a previous pyeloplasty for PUJO which demanded intervention. Mean split function on renography was 11% (range 0–46%). Selective renal artery embolization was carried out under antibiotic cover using a 7 Fr balloon occlusion catheter and absolute alcohol, steel coils, and polyvinyl alcohol particles.Results: Nine patients developed post-embolization syndrome of self-limiting pain and pyrexia with no evidence of sepsis. One patient required readmission with this condition. One patient developed a hematoma at the puncture site. Mean hospital stay was 2.3 days. Fourteen patients are happy with the result and are completely pain free. One patient has minor discomfort but is delighted with the result. Nine patients have had follow-up ultrasound confirming resolution of the hydronephrosis. Conclusion: Renal artery embolization is an effective, safe, well-tolerated minimally invasive treatment option in end-stage hydronephrosis and we routinely offer it as an alternative to nephrectomy.

Self-expanding metallic stents in the management of pyloric dysfunction after gastric pull-up operations.

Abstract. The purpose of this paper is to report the use and benefits of self-expanding metallic stents employed in pyloric dysfunction. Four patients treated with oesophagectomy and gastric pull-up for oesophageal carcinoma failed to respond to balloon dilatation for pyloric dysfunction. Three of the patients were thought to have residual tumour at sites remote from the pylorus prior to stenting, but the fourth, who had undergone surgery 8 years previously, was thought to be cured. All were treated with self-expanding metallic stents. All four patients responded well with resolution of their symptoms. Over a mean follow-up of 6 months there has been no recurrence of symptoms. Stent insertion represents a potentially valuable method of treatment in patients with post-surgical pyloric dysfunction in whom simple balloon dilatation has failed.

Epirubicin, cisplatin, and prolonged or brief infusional 5-fluorouracil in the treatment of carcinoma of unknown primary site

The cytotoxic regimen of epirubicin, cisplatin, and continuous infusional 5-fluorouracil (ECF) has demonstrated activity in a range of malignancies, including gastroesophageal, breast, and pancreatic cancers. Prolonged infusional central venous catheter (CVC) mediated therapy is not always feasible and modifications of the 5-fluorouracil (5FU) schedule have been reported. We reviewed our experience of both the standard and a modified ECF regimen in patients diagnosed with carcinoma of unknown primary site (CUPS). A retrospective analysis of all patients diagnosed with CUPS (31 adenocarcinoma and 5 poorly differentiated carcinoma) and treated with ECF between June 1994 and June 1998 was undertaken. Thirty-six patients, median age 56 (range: 24–74), were treated thrice-weekly with 50 mg/m2 epirubicin, 60 mg/m2 cisplatin, and 5-FU administered either by continuous infusion 200 mg/m2/d via a CVC (standard ECF) or as a 6-h infusion 600 mg/m2 through a peripheral venous catheter (modified ECF). Thirteen patients were treated with standard ECF and 23 received modified ECF. The median number of cycles administered was 4 (range: 1–10). Thirty-two patients had evaluable disease, seven (22%; 95% confidence interval: 8–36%) demonstrated a partial response, including three patients that received standard ECF and four treated with modified ECF. There were no complete responses. The median survival for all 36 patients was 9.0 mo. Median survival for patients treated with standard ECF was 11.7 mo as compared to 5.1 mo for the modified ECF schedule (p=0.052). Liver involvement and elevation of serum CA19.9 were identified as possible adverse prognostic factors. Both regimens were well tolerated, with the only grade 3/4 toxicity recorded being leukopenia (four patients), nausea/vomiting (seven patients), and diarrhea (one patient). CVC complications in the standard ECF group were thrombosis (one patient) and infection (three patients). There were no treatment-related deaths. We conclude that ECF, whether modified or standard, has modest activity in the setting of CUPS. Patient survival is comparable to survival documented in previous reports of CUPS treatment. The apparent survival difference between the two ECF schedules may be the result of patient selection factors. The optimal treatment of CUPS remains unknown and can only be determined through randomized controlled trials.

Assessment of Peripheral Vascular Disease

The decision to perform an endovascular procedure is crucially dependent upon proper patient assessment. This in the first instance involves a thorough history and examination to determine the severity of symptoms and the impact that they are having on the patients lifestyle. Further clinical assessment is most frequently carried out by determining the ankle brachial index. Increasingly non-invasive imaging methods are used to determine the locations of relevant lesions prior to endovascular intervention.

Esophageal and upper GI stenting

Self-expanding metallic stents are now well established in the palliative management of inoperable esophageal carcinoma. Dysphagia is successfully palliated in more than 90% of patients treated, with a low incidence of procedural complications. Use of covered stents minimizes recurrent dysphagia due to tumor ingrowth, and also provides palliation for the vast majority of malignant esophageal perforations and fistulae to the airways. However, these stents cannot be used at the esophagogastric junction because there is a high incidence of stent migration when they are used at this site. Use of stents in benign disease of the esophagus is limited by the high incidence of epithelial hyperplasia that occurs over follow-up. Stents may also be used in the relief of inoperable gastric outflow obstruction caused either by gastric or pancreatic carcinoma. The numbers of cases published in the literature are relatively small, but results indicate successful palliation with no reported complications at this time.