The addition of deep hyperthermia to gemcitabine-based chemoradiation may achieve enhanced survival in unresectable locally advanced adenocarcinoma of the pancreas.

INTRODUCTION: Driven by the current unsatisfactory outcomes for patients with locally advanced pancreatic cancer (LAPC), a biologically intensified clinical protocol was developed to explore the feasibility and efficacy of FOLFORINOX chemotherapy followed by deep hyperthermia concomitant with chemoradiation and subsequent FOLFORINOX chemotherapy in patients with LAPC. METHODS: Nine patients with LAPC were treated according to the HEATPAC Phase II trial protocol which consists of 4 cycles of FOLFORINOX chemotherapy followed by gemcitabine-based chemoradiation to 56 Gy combined with weekly deep hyperthermia and then a further 8 cycles of FOLFORINOX chemotherapy. RESULTS: One grade three related toxicity was reported and two tumours became resectable. The median overall survival was 24 months and 1 year overall survival was 100%. CONCLUSIONS: Intensification of chemoradiation with deep hyperthermia was feasible in nine consecutive patients with LAPC.

[Self-expanding wire-netting Elastalloy endoprosthesis in malignant esophageal stenosis]. / Selbstexpandierende Maschendrahtendoprothesen aus Elastalloy bei malignen Osophagusstenosen.

12 patients with malignant inoperable esophageal obstruction (carcinoma of the esophagus n = 7, carcinoma of the esophagogastric junction n = 3, mediastinal lymph node metastasis n = 2) and high-grade dysphagia were treated with self-expanding metal stents (Ultraflex, Microvasive) made of a nickel titanium alloy (Elastalloy). Other forms of palliation had failed in 9/12 patients. The degree of palliation was expressed as a dysphagia score (0-4) before and after stent insertion. The stents were inserted under endoscopic and fluoroscopic control. They were placed successfully and without complications in all patients. A good functional result was achieved in 11 patients (91.7%). Thus, the dysphagia score decreased significantly from 3.2 +/- 0.4 before to 0.9 +/- 1.0 immediately after stent insertion (p < 0.001). The remarkable relief of dysphagia was sustained during a mean follow up of 101 days (10-278) with a dysphagia score of 1.1 +/- 1.0 at the end of the study (p < 0.001 compared to the score before the procedure). In one patient with mediastinal lymph node metastasis the stent expanded insufficiently. 7 days after insertion it was removed endoscopically and replaced successfully by another stent with a stronger expansive force (Instent). 3 patients experienced recurrent dysphagia (food impaction n = 1 tumor ingrowth through the meshes of the stent n = 2). They were successfully treated by an endoscopical intervention (endoscopical dilatation n = 1, laser therapy n = 1, insertion of a Wallstent n = 1). At the end of the study, 6 patients were alive, 6 patients were dead with a mean survival of 56 days (10-117).

Effect of secretin on bile formation in rats with cirrhosis of the liver: structure-function relationship.

To investigate whether the hypercholeresis seen in cirrhotic humans and animals is due to ductular proliferation or altered inactivation of secretin, or both, we studied the response of bile flow and biliary erythritol clearance to synthetic porcine secretin in rats rendered cirrhotic by chronic exposure to phenobarbital/carbon tetrachloride (n = 11) and untreated control rats (n = 5). Bile duct mass was determined morphometrically. Furthermore, plasma disappearance of secretin was measured by radioimmunoassay. Basal bile flow did not differ between the two groups. Whereas secretin had no effect in the control group, it stimulated bile flow by 49% +/- 33% in the cirrhotic group (p less than 0.001). Erythritol bile-to-plasma ratio was lower and biliary bicarbonate concentration higher in the cirrhotic rats, suggesting some ductular contribution to bile flow even in the absence of secretin. Biliary bicarbonate concentration did not increase further during secretin administration, whereas bile salt concentration decreased from 27 +/- 6 to 18 +/- 4 mM. The elimination half-life of secretin was not affected by cirrhosis, averaging 5 +/- 2 min in both groups. Bile duct volume was increased in cirrhotics (2.9% +/- 1.4% vs. 0.2% +/- 0.1%; p less than 0.01) and showed an excellent correlation with the maximal secretin-induced increment of bile flow. Our results suggest that the proliferating ductules contribute to bile flow and that increased secretin responsiveness is not due to altered pharmacokinetics in cirrhotic rat liver.

Wallstents versus plastic stents in malignant biliary obstruction: effects of stent patency of the first and second stent on patient compliance and survival.

OBJECTIVES: In prospective trials in patients with malignant biliary obstruction, it has been reported that Wallstents prolong stent patency, but this does not translate into a significant survival benefit. Compared with prospective trials, however, survival may be different in clinical practice because of differences in patient compliance. We report on a retrospective, long term analysis comparing Wallstents versus plastic stents. METHODS: Plastic endoprostheses (70 patients) and endoscopic Wallstents (95 patients) were placed in 165 consecutive patients with irresectable, malignant biliary obstruction in a first (1990-91) and second (1992-93) time period. Stent occlusion was treated by plastic stent placement. RESULTS: Patient characteristics were quite comparable in both stent groups. Initial placement of a Wallstent resulted in an increase of median stent patency of the first (10 vs 4 months, p < 0.001) and second (8 vs 3 months, p < 0.05) stent, a decrease of additional endoscopic procedures (20 vs 58%, p < 0.005), an increase of patient compliance reflected by a decrease of patients dying with untreated stent occlusion (9 vs 30%, p < 0.001), and an increase of survival time (6.5 vs 4 months, p < 0.05). CONCLUSIONS: Initial placement of a Wallstent results in an increase of stent patency of the first and second stent. Duration of stent patency appears to have a determinant effect on patient compliance. Increased stent patency and patient compliance seem to improve survival in clinical practice.

Long-term follow-up after treatment of common bile duct stones by extracorporeal shock-wave lithotripsy.

BACKGROUND AND STUDY AIMS: The efficacy of extracorporeal shock-wave lithotripsy (ESWL) of difficult bile duct stones that were not amenable to routine endoscopic extraction was assessed, with evaluation of the long-term follow-up after successful treatment. PATIENTS AND METHODS: Fifty-four patients (mean age 74 years, range 33-92) were treated with ESWL for difficult bile duct stones. Treatment was performed either with the Dornier HM3 kidney lithotriptor (49 patients) or with the MPL 9000 lithotriptor (five patients). RESULTS: Stone disintegration was achieved in 50 patients (93%), with complete stone clearance in 45 patients (83%) (mean 1.2 session). Patients with successful stone removal after one session had significantly smaller stones than patients with treatment failure (20 +/- 9 versus 27 +/- 8 mm; p < 0.05). An intrahepatic location of stones was significantly associated with treatment failure (p < 0.005). Serve complications occurred in 7% (procedure-related 5%), with a 30-day mortality rate of 0% (in-hospital mortality rate of 2%). Minor side effects such as fever, petechiae, and mild arrhythmias were frequent (37%), and microhematuria (95%) occurred in nearly all of the patients. Symptomatic recurrent bile duct stones were observed in two patients (5%) after three and four years, respectively (mean follow-up 5.3 years). CONCLUSION: Extracorporeal shock wave lithotripsy represents a safe and effective treatment modality for difficult bile duct stones, with a low rate of symptomatic recurrences.

Self-expanding metal stents in malignant esophageal obstruction: a comparison between two stent types.

OBJECTIVES: Self-expanding metal stents are a promising alternative in the palliation of malignant esophageal obstruction, but the relative value of different stent types is not well established. METHODS: During a 3-year enrollment period in four different centers, 82 consecutive patients with malignant dysphagia without tumor recurrence after surgery or esophagorespiratory fistulas received either an uncovered Wallstent (44 patients) or a knitted nitinol stent (38 patients). RESULTS: Age (median: 79 yr), sex (F:M = 33:67), dysphagia score (median: 3), Karnofsky score (median: 53), body mass index (median: 19), type of pretreatment, tumor stage, stricture length (median: 5.4 cm), and stricture location were comparable in both stent groups. After stent placement, median dysphagia score improved markedly in both groups by two points. Procedure-related mortality (16 vs 0%; p < 0.01), early complication rate (32 vs 8%; p < 0.01), and severe persistent pain after stent placement (23 vs 0%; p < 0.002) were higher in the Wallstent compared with the knitted nitinol stent group. In contrast, stent dysfunction (7 vs 32%; p < 0.005), reintervention rate (9 vs 34%; p < 0.005), and costs were lower in the Wallstent compared with the nitinol stent group. CONCLUSIONS: In malignant esophageal obstruction, both stents markedly improved dysphagia. Uncovered Wallstents seem to cause more early severe complications than knitted nitinol stents. In contrast, stent dysfunction, reintervention rate, and costs appear to be higher in the nitinol stent group.