Search

Background & Aims:: In nonrandomized trials, photodynamic therapy (PDT) had a promising effect on nonresectable cholangiocarcinoma (NCC). This prospective, open-label, randomized, multicenter study with a group sequential design compared PDT in addition to stenting (group A) with stenting alone (group B) in patients with NCC. Methods:: In patients with histologically confirmed cholangiocarcinoma, endoscopic or percutaneous double stenting was performed. Patients fulfilling inclusion criteria were randomized to group A (stenting and subsequent PDT) and group B (stenting alone). For PDT, Photofrin 2 mg/kg body wt was injected intravenously 2 days before intraluminal photoactivation (wavelength, 630 nm; light dose, 180 J/cm^2). Further treatments were performed in cases of residual tumor in the bile duct. The primary outcome parameter was survival time. Secondary outcome parameters were cholestasis and quality of life. Results:: PDT resulted in prolongation of survival (group A: n = 20, median 493 days; group B: n = 19, median 98 days; P < 0.0001). It also improved biliary drainage and quality of life. Conclusions:: PDT, given in addition to best supportive care, improves survival in patients with NCC. The study was terminated prematurely because PDT proved to be so superior to simple stenting treatment that further randomization was deemed unethical.

Background: Malignant duodenal obstruction is a common event in patients with advanced biliary tract cancer. Because bypass surgery is accompanied by significant morbidity, self-expandable metallic stents have emerged as a possible alternative for palliation. Methods: Twenty patients with biliary tract cancer (7 gallbladder, 13 Klatskin tumors) and duodenal obstruction were treated with metallic stents at a single institution between 1999 and 2001. Survival, morbidity, and stent function were studied prospectively. The ability to eat was assessed by using a scoring system. Results: Stent placement was technically successful in all patients. An additional stent was required in 6 cases (4 occlusions, 2 dislocations). Median survival was 20.5 weeks; there was no treatment-related death. Twenty-eight biliary stent exchanges were performed in 13 (65%) patients. Erosive reflux esophagitis improved in 11 of 12 (92%) cases. After 4 weeks, all 17 surviving patients tolerated soft or solid food, whereas 13 of 17 (77%) tolerated a more solid diet (p<0.001, gastric outlet obstruction scoring system). Twelve of 17 (71%) patients gained a median of 1.5 kg of body weight (p=0.001). The median Karnofsky scale increased from 50% to 60% in 13 of 17 (77%) patients. Conclusions: Self-expandable metallic stents are a safe, efficacious, and minimally invasive treatment option for palliation of patients with duodenal obstruction from biliary tract cancer. Technical complications can be managed endoscopically and the bile duct remains accessible for endoluminal treatment.

We demonstrate the use of Lee−Goldburg cross-polarization (LG-CP) NMR under fast magic-angle spinning (MAS) to investigate the amplitude and geometry of segmental motions in biomolecular and polymeric solids. Motional geometry information was previously available only from ²H NMR, which, however, has limited site resolution and requires site-specific isotopic labeling. Using a 2D LG-CP technique, we resolve the ¹³C−¹H or ¹⁵N−¹H dipolar couplings according to the ¹³C or ¹⁵N isotropic chemical shift. Applications to systems undergoing 180° phenylene ring flips show spectral line shapes reflecting the geometry of the motion. Using this LG-CP technique, we measured the ¹³C−¹H and ¹⁵N−¹H dipolar couplings in the water-soluble and membrane-bound states of the colicin Ia channel domain. The backbone motions of the membrane-bound colicin scale both the Cα−Hα and N−H couplings similarly, thus ruling out rotation of the α-helices around their axes as a specific mechanism of motion. We also show that the sensitivity of the LG-CP spectra can be enhanced by the addition of a phase-inverted ¹H−¹³C cross-polarization step, and the site resolution of the ¹⁵N−¹H LG-CP spectra can be enhanced by ¹³C indirect detection.