Super-selective hepatic arterial infusions as established technique ('ARETAIEION' Protocol) of [177Lu]DOTA-TATE in inoperable neuroendocrine liver metastases of gastro-entero-pancreatic (GEP) tumors.

AIM: Aim of this study was to evaluate the effectiveness of non-carrier added (n. c. a.) [177Lu]DOTA-TATE in inoperable liver metastases, positive for sst2 receptor overexpression (verified by Octreoscan and confirmed by biopsy) due to neuroendocrine gastroenteropancreatic (GEP) tumors. [177Lu]DOTA-TATE has been infused after selective catheterization of the hepatic artery, minimising in parallel the toxicity of non-target tissues. METHODS: The dose per session administered to each patient (12 cases in total) was 7400 MBq (200 mCi). Repetitions did not exceed 6-fold with treatment intervals of 5-8 weeks. Response assessment was classified according to the therapeutic benefit. Absorbed doses delivered to metastases, kidneys and red marrow were calculated according to OLINDA 1.1 program and the derived values were correlated to the Response Evaluating Criteria in Solid Tumors (RECIST). CT/MRI scans were performed as baseline before, during and after the end of treatment and monthly ultrasound images for follow-up estimation and measurements. Toxicity (World Health Organization criteria) was measured using blood and urine tests of renal, hepatic and bone marrow function. RESULTS: None of the patients resulted complete response (0.0%); partial response was assessed in 8 (66.7%), disease stabilization in 3 (25%) and progressive disease in 1(8.3%). A 14-month median survival time was estimated for all patients, so far. Eight of 12 (66.7%) showed a mean target diameter shrinkage ranging from 33% to 45%. The organ average radiation dose estimation was found as follows: a) liver tumor 20.8 mGy/MBq; b) liver 0.14 mGy/MBq; c) kidneys 0.41 mGy/MBq; d) spleen 1.4 mGy/MBq; and f) bone marrow 0.022 mGy/MBq. The average absorbed dose per session to a tumor for a spherical mass of 20 g was estimated to be 20.8 mGy/MBq, depending on the histotype of the tumor. WHO toxicity grade 2 to 3 erythro-, leuko- and thrombo-cytopenia occurred in 9 (75%) cases observed about after the third session. CONCLUSION: In unresectable metastatic liver lesions positive for somatostatin receptors repeated, trans-hepatic high doses of [177Lu]DOTA-TATE resulted in a more than promising therapeutic outcome with a partial response in 75% of the treated patients. Given the loco-regional modality character of the administration technique, no nephro-toxicity has been so far observed whereas a remarkable myelotoxicity was noticed.

Are metal stents effective for palliation of malignant dysphagia and fistulas?

BACKGROUND: One of the available treatments for unresectable oesophagogastric malignancies is the insertion of metal stents. AIMS: We evaluated prospectively 147 patients suffering from malignant dysphagia and/or fistula, after inserting a self-expandable metal stent. PATIENTS AND METHODS: The study included 147 patients (87 males, mean age 73 years). Dysphagia before and after stent placement was scored. Patients were divided in two groups according to dysphagia grade: group A (grade 0, 1) and group B (grades 2, 3, 4). Three types of stents were used: the Ultraflex stent (covered and uncovered) and the Flamingo one (covered). The total number of self-expandable metal stents placed was 183. A total of 92 of them were inserted following the combined endoscopic and fluoroscopic approach (42 by injecting lipiodol), while 91 were placed under endoscopic control only. Early and late complications were evaluated. RESULTS: Mean dysphagia score in group A, 1 day and 1 month after the procedure, was slightly reduced from 0.8 to 0.5/0.6 (p=NS), respectively. However, there was a statistically significant improvement (p<0.001) of mean dysphagia score in group B, from 2.4 initially to 1.1/1.4. Early complications occurred in 37 cases, late ones in 51. According to severity, minor complications occurred in 24 patients, major in 42, while life-threatening ones in 22. Survival ranged from 1 to 611 days and 1-week mortality was 9%. Stent-related death occurred in six patients. CONCLUSIONS: All kinds of endoscopic methods used for stenting in the present study were easy to perform even on an out-patient basis. Insertion of self-expandable metal stents is effective in patients with dysphagia scores > or = 2. It might not clinically improve patients with dysphagia score <2, so selection of patients for stenting is essential to avoid unnecessary procedures. Moreover, their high cost, high complication rates and low overall survival may improve following better selection criteria.

Palliation of proximal malignant biliary obstruction by endoscopic endoprosthesis insertion.

For four years up to December 1987, 190 patients (median age 73 years) with proximal malignant biliary obstruction were treated by endoscopic endoprosthesis insertion. Altogether 101 had cholangiocarcinoma, 21 gall bladder carcinoma, 20 local spread of pancreatic carcinoma, and 48 metastatic malignancy. Fifty eight patients had type I, 54 type II, and 78 type III proximal biliary strictures (Bismuth classification). All patients were either unfit or unsuitable for an attempt at curative surgical resection. A single endoprosthesis was placed initially, with a further stent being placed only if relief of cholestasis was insufficient or sepsis developed in undrained segments. The combined percutaneous-endoscopic technique was used to place the endoprosthesis when appropriate, after failed endoscopic endoprosthesis insertion or for second endoprosthesis placement. Full follow up was available in 97%. Thirteen patients were still alive at the time of review and all but one had been treated within the past six months. Initial endoprosthesis insertion succeeded technically at the first attempt in 127 patients, at the second in 30, and at a combined procedure in a further 13 (cumulative total success rate 89% - type I: 93%; type II: 94%; and type III: 84%). There was adequate biliary drainage after single endoprosthesis insertion in 152 of the 170 successful placements, giving an overall successful drainage rate of 80%. Three patients had a second stent placed by combined procedure because of insufficient drainage, giving an overall successful drainage rate of 82% (155 of 190). The final overall drainage success rates were type I: 91%; type II: 83%; and type III: 73%. The early complication rates were type I: 7%; type II: 14%; and type III: 31%. The principle early complication was clinical cholangitis, which occurred in 13 patients (7%) and required second stent placement in five. The 30 day mortality was 22% overall (type I: 14%; type II: 15%; and type III: 32%) but the direct procedure related mortality was only 3%. Median survival overall for types I, II, and III strictures were 21, 12, and 10 weeks respectively but survival was significantly shorter for metastatic than primary malignancy (p<0.05). Endoscopic insertion of a single endoprosthesis will provide good palliation of proximal malignant biliary obstruction caused by unresectable malignancy in 80% of patients. Second stents should be placed only if required. Extensive structuring because of metastatic disease carries a poor prognosis and careful patient selection for treatment is requires.

Needle knife papillotomy: how safe and how effective?

Between January 1986 and July 1988 needle knife papillotomy was attempted in 103 patients after failure of conventional access for endoscopic sphincterotomy (96 cases) or diagnostic cholangiography (seven cases). Access was obtained at the same session in 36 cases and at a subsequent attempt within 2 to 5 days in a further 43, an overall success rate of 77%. The procedure related morbidity and mortality in the therapeutic group were 5.2% and 2.0% respectively. There were no deaths or complications in the diagnostic group. Needle knife papillotomy is a valuable adjunct to conventional techniques of biliary access.

A comparison of right versus left hepatic duct endoprosthesis insertion in malignant hilar biliary obstruction.

Endoscopic endoprosthesis insertion plays an increasingly important role in the palliation of jaundice in patients with unresectable malignant hilar biliary obstruction (HBO). Drainage of both obstructed lobes in Types II and III HBO is not necessary to achieve adequate palliation, providing 25% of the liver volume is drained by a single endoprosthesis. The anatomy of the main hepatic ducts suggests some benefit may accrue from preferential drainage of the left hepatic duct. We have reviewed a consecutive series of 151 patients with Type II and III HBO over a 4-year period to compare the outcome of endoprosthesis placement in either the right (RHD) or left (LHD) hepatic duct, to test this hypothesis. No significant difference was found in terms of successful drainage, complications, 30-day mortality, number of endoprosthesis changes and survival between patients with right system drainage compared with those with left sided drainage (chi 2-test and Mann Whitney U test). When dealing with a patient with a Type II or III HBO, we would recommend single endoscopic endoprosthesis insertion into the technically most accessible obstructed system. This would achieve adequate palliation in 84% of the patients.

Is duodenal diverticulum a risk factor for sphincterotomy?

It is uncertain whether ERCP and associated procedures are more difficult when the papilla is inside or adjacent to a duodenal diverticulum. We have therefore reviewed the data from 2458 consecutive, prospectively reported ERCPs between November 1983 and March 1988. Three hundred and eight patients (12.5%) had periampullary diverticula and in 21 the papilla was located deep within the diverticulum of whom 227 had undergone endoscopic sphincterotomy (73.7%). Comparison was made with the 2150 patients without diverticula of whom 1223 (56.9%) had undergone sphincterotomy. The success rate of specific duct cannulation was 94.2% in the diverticulum group and 96.7% in those without diverticula (p less than 0.05). The overall success rate of endoscopic sphincterotomy was 95.2% in the diverticulum group, as compared with 98.0% in those without diverticula (p less than 0.05). The procedure related morbidity and mortality of sphincterotomy were 5.2%/0.9% and 4.0%/0.7% respectively (NS). If only those who had successful cholangiography were included there was no difference in sphincterotomy success between those with and without diverticula. The group of patients with papilla deep within diverticula had a slightly higher failure rate of pure endoscopic sphincterotomy (11.8% v 5.7%: NS) but did not have a higher complication rate. In the subgroup of patients with choledocholithiasis, duct clearance of stones was as successful after sphincterotomy in those with diverticula as in those without. Medium term complications (mean 26 months) occurred in 1.4% of patients with diverticula and in 0.7% of patients without diverticula. We conclude that diagnostic cholangiography is more difficult when the papilla is closely associated with a diverticulum but that if diagnostic cholangiography is obtained, sphincterotomy may be performed as successfully and as safely in those with or without diverticula.

Endoscopic endoprosthesis insertion following failure of cholecystojejunostomy in pancreatic carcinoma.

Sixteen patients in whom malignant biliary obstruction recurred after failure of cholecystojejunostomy had attempted relief of obstruction by endoscopic insertion of an endoprosthesis. This treatment was successful in 13 patients, although one required percutaneous insertion because of duodenal distortion and one required a combined percutaneous-endoscopic approach. Median survival after stenting was 3.5 months (range from 2 weeks to 16 months). Of the three treatment failures, two patients had external drainage only and one succumbed before further treatment could be attempted. There were two complications associated with the procedure (one small bile leak and one episode of cholangitis) but the 30-day mortality rate of 12.5 per cent was related to disease progression rather than the procedure. Endoscopic stent insertion may achieve further worthwhile palliation of jaundice after the failure of surgery to relieve malignant biliary obstruction.