Jürgen F. Riemann

Palliation of Nonresectable Bile Duct Cancer: Improved Survival After Photodynamic Therapy

OBJECTIVES:Preliminary uncontrolled studies of photodynamic therapy (PDT) of bile duct cancer (BDC) have shown astonishingly good results in the reduction of cholestasis, improvement of life quality, and potential improvement of survival time. Therefore, we investigated the influence of PDT on survival time in advanced BDC in a randomized controlled study.METHODS:Thirty-two patients with nonresectable BDC were randomized. In the PDT group 48 h after intravenous application of 2 mg/kg body weight of Photosan-3®, light activation was performed. In the control group, patients were treated with endoprostheses but no PDT.RESULTS:PDT group and the control group were comparable due to age, gender, performance status, bilirubin level, and BDC stage (Bismuth classification). The median survival time after randomization was 7 months for the control group and 21 months for the PDT group (p = 0.0109). In half of the initially percutaneously treated patients, we could change from percutaneous to transpapillary drainage after PDT. Four patients showed infectious complications after PDT versus one patient in the control group.DISCUSSION:PDT is minimally invasive but shows a considerable postinterventional cholangitis rate. PDT has the potential to result in a changeover of current palliative treatment of BDC.

A prospective study of the diagnostic accuracy of PillCam ESO esophageal capsule endoscopy versus conventional upper endoscopy in patients with chronic gastroesophageal reflux diseases

Introduction: Endoscopy is commonly performed to evaluate for suspected or established esophageal diseases including gastroesophageal reflux disease (GERD) and its complications. The newly developed PillCam ESO Esophageal Capsule offers an alternative approach to visualize the esophagus and to evaluate patients with suspected esophageal disease. Aim: Compare the accuracy (specificity, sensitivity, positive predictive value [PPV], and negative predictive value [NPV]) of esophageal capsule endoscopy (ECE) compared with esophagogastroduodenoscopy (EGD) in evaluating patients with GERD. Methods: A multicenter pivotal trial was conducted at seven sites. The PillCam ESO esophageal capsule is similar to the standard capsule endoscope used for the small bowel but acquires video images from both ends of the device at 2 frames/second/end. A total of 106 patients (93 GERD; 13 Barrett) underwent ECE followed by EGD. ECE videos were evaluated by an investigator blinded to EGD findings. A blinded adjudication committee reviewed all discrepant findings between ECE and EGD. Results: Sixty-six of 106 patients had positive esophageal findings, ECE identified esophageal abnormalities in 61 (sensitivity, 92%; specificity, 95%). The per-protocol sensitivity, specificity, PPV, and NPV of ECE for Barrett esophagus were 97%, 99%, 97%, and 99%, respectively, and for esophagitis 89%, 99%, 97%, and 94%, respectively. ECE was preferred over EGD by all patients. There were no adverse events related to ECE. Conclusions: ECE is a convenient and sensitive method for visualization of esophageal mucosal pathology and may provide an effective method to evaluate patients for esophageal disease.

Computer-assisted colonoscopy (the NeoGuide Endoscopy System): results of the first human clinical trial ("PACE study").

OBJECTIVES:Unsedated colonoscopy is an uncomfortable procedure for most patients. Discomfort during colonoscopy is largely related to looping of the colonoscope, which displaces the colon from its native configuration and stretches attachments to the mesentery. A novel computer-assisted colonoscope utilizes a fully articulated, computer-controlled insertion tube. On manual insertion of the colonoscope, the position and angle of the scopes tip are encoded into a computer algorithm. As the colonoscope is advanced, the computer directs each successive segment to take the same shape that the tip had at a given insertion depth. The insertion tube thus changes its shape at different insertion depths in a “follow-the-leader” manner.METHODS:This initial clinical trial with this novel colonoscopy system was designed as a prospective, nonrandomized, unblinded, feasibility study. Three physicians of varying levels of experience participated in the study.RESULTS:Eleven consecutive patients (seven men, four women, age range 19–80) meeting inclusion criteria for screening or diagnostic colonoscopy were enrolled in the study. The cecum was reached in 10 consecutive patients (100%). Findings included diverticular disease in two cases and multiple colonic polyps in two cases. Postprocedure assessment at discharge, 48 h, and 30 days revealed no complications or adverse effects. Physician satisfaction and patient acceptance of this new technique were high.CONCLUSIONS:In this limited, first of its kind feasibility study, the computer-assisted colonoscope was shown to perform colonoscopy safely and effectively. The colonoscopes unique design limited loop formation during colonoscopy. Large-scale clinical trials are indicated.

Endoscopic stenting for common bile duct stenoses in chronic pancreatitis: results and impact on long-term outcome.

Objectives The overall incidence of common bile duct strictures due to chronic pancreatitis is reported to be approximately 10–30%. It remains a challenging problem for gastroenterologists and surgeons. The exact role of endoscopic stenting has not yet been clearly defined. Design and methods Thirty-nine patients with chronic pancreatitis and symptomatic common bile duct stenoses underwent endoscopic stenting and were studied retrospectively. We were particularly interested in how many patients would achieve resolution of the stricture and tolerate removal of the stents in the long term. Results Indications for endoscopic stenting were symptomatic cholestasis, jaundice or cholangitis. The initial serum bilirubin was 8.3 mg/dl and the diameter of the common bile duct was 14.2 mm before stenting. Within 3–7 days of stenting, all patients presented improvement of jaundice and cholestasis. After a median stenting time of 9 months (range 1–144 months), 46% of the patients demonstrated regression of the stricture and clinical improvement, 26% required further stenting, and 28% were referred to surgery. Five patients received a self-expandable metal Wallstent. Thirty-one per cent demonstrated complete clinical recovery of the stricture as well as 10.2% a complete, radiologically verified stricture regression in a median follow-up of 58 months. Conclusions There seems to be a therapeutic benefit for short-term endoscopic treatment but medium-term and long-term outcome remains questionable. Endoscopic stenting should be applied as an initial therapy before surgery, but it can be the definitive approach for older and morbid patients or cases with complete stricture regression after stent removal. Overall, it should not be considered as a routine procedure for symptomatic cases.

Photodynamic therapy for palliation of nonresectable bile duct cancer—preliminary results with a new diode laser system

OBJECTIVES:Preliminary results of photodynamic therapy (PDT) of bile duct cancer have shown astonishingly good results in the reduction of cholestasis, improvement of quality of life, and even prolongation of the survival time. Unfortunately, the existing dye laser systems are large and costly, and their maintenance is expensive. Therefore, we investigated the feasibility of a diode laser system for PDT of nonresectable bile duct cancer.METHODS:Eight patients with nonresectable bile duct cancer were treated. Forty-eight hours after i.v. application of 2 mg/kg body weight of Photosan-3, light activation was performed by a transpapillary (four patients) or percutaneous (four patients) access. We used a cylindrical diffusor tip and illuminated using a wavelength of 633 ± 3 nm and a total energy of 200 J/cm2. All patients were additionally provided with bile duct endoprostheses after PDT.RESULTS:Four weeks after initial PDT all patients showed a marked reduction of bile duct stenosis. The median serum bilirubin value declined from 5.8 mg/dl (2.0–10.1) to 1.0 mg/dl (0.8–4.4). The median survival time at the time of writing is 119 days (52–443). Five patients are still alive. In four patients we could change from percutaneous to transpapillary drainage after PDT, two patients showed infectious complications.CONCLUSION:PDT with the diode laser system seems to be effective in reducing malignant bile duct stenosis. This treatment is minimally invasive and has a low specific complication rate. Randomized, controlled studies comparing PDT with the insertion of endoprostheses and long term follow-up of results are needed to confirm the promising short term results.

Buprenorphine or procaine for pain relief in acute pancreatitis. A prospective randomized study.

Background: To assess the analgesic efficacy and side effects of buprenorphine and procaine in patients with acute pancreatitis. Methods: Forty patients (average age, 50 years; 23 male) with acute pancreatitis or an acute bout of a chronic pancreatitis were prospectively randomized to receive buprenorphine or procaine for pain relief. Both analgesics were administered as constant intravenous (i.v.) infusions and additional analgesics were given on demand. Pain scores were assessed on a visual analogue scale. Close clinical control and laboratory checks were performed during the three-day study period. Results: Patients receiving buprenorphine were significantly less likely to demand additional analgesics (1 versus 14 patients; P < 0.0001). The pain scores for patients in the buprenorphine group were significantly lower over the treatment period in comparison to procaine (P < 0.05). The reduction of pain score was significantly greater during the initial two treatment days using buprenorphine (day 1: 55 versus 25, P < 0.0001; day 2: 62 versus 40, P = 0.005). Side effects were comparable for both groups with the exception of a slightly higher sedation rate under buprenorphine. Conclusions: Constant i.v. application of buprenorphine is more effective than the recommended procaine for pain relief in acute pancreatitis.BACKGROUND To assess the analgesic efficacy and side effects of buprenorphine and procaine in patients with acute pancreatitis. METHODS Forty patients (average age, 50 years; 23 male) with acute pancreatitis or an acute bout of a chronic pancreatitis were prospectively randomized to receive buprenorphine or procaine for pain relief. Both analgesics were administered as constant intravenous (i.v.) infusions and additional analgesics were given on demand. Pain scores were assessed on a visual analogue scale. Close clinical control and laboratory checks were performed during the three-day study period. RESULTS Patients receiving buprenorphine were significantly less likely to demand additional analgesics (1 versus 14 patients; P < 0.0001). The pain scores for patients in the buprenorphine group were significantly lower over the treatment period in comparison to procaine (P < 0.05). The reduction of pain score was significantly greater during the initial two treatment days using buprenorphine (day 1: 55 versus 25, P < 0.0001; day 2: 62 versus 40, P = 0.005). Side effects were comparable for both groups with the exception of a slightly higher sedation rate under buprenorphine. CONCLUSIONS Constant i.v. application of buprenorphine is more effective than the recommended procaine for pain relief in acute pancreatitis.

Spontaneous Esophagotracheal Fistula Resulting From Ulcer in Heterotopic Gastric Mucosa

In a 50-yr-old male patient, a spontaneously perforating peptic ulcer located in a patch of heterotopic gastric mucosa in the upper part of the esophagus led to the development of an esophagotracheal fistula. The histologic workup revealed, in addition to ulcer necroses and granulation tissue, glands of the fundic type, with chief and parietal cells. On the basis of histologic results, the fistula was successfully occluded with the aid of a fibrin adhesive applied endoscopically. After the second session, the patient immediately became free of symptoms. Under medical treatment with an H2-receptor blocker, the patient has been completely symptom-free for 1 yr.

Acute Ulcer Bleeding (A Prospective Randomized Trial to Compare Doppler and Forrest Classifications in Endoscopic Diagnosis and Therapy)

The aim of our prospective randomized studyinvolving 100 patients was to investigate whetherDoppler ultrasound can be used to select patients atrisk for ulcer rebleeding. Ulcers in the Forrest group classified as having a visible vessel or a clotwere treated prophylactically by injection withepinephrine solution. In the Doppler group, in contrast,only ulcers with a positive Doppler signal were treated endoscopically. In the Doppler group, rebleedsoccurred significantly less frequently (2%, P < 0.03)than in the Forrest group (14%). Emergency surgery wasonly necessary in the Forrest group (0% vs 5%; P =0.02). Bleeding-related mortality was 0% and 4% (P =0.15) and the overall mortality 0% and 10% (P = 0.02),in the Doppler and Forrest groups, respectively. Theseresults appear to show that Doppler-based injection treatment is superior to endoscopictreatment based exclusively on the Forrestclassification. In our study, Doppler-based localendoscopic treatment reduced the danger of a rebleed andthus the number of emergency operations and the overallmortality.

Management of Esophageal Perforations after Therapeutic Upper Gastrointestinal Endoscopy

BACKGROUND Esophageal perforation is one of the most dreaded complications in therapeutic gastrointestinal endoscopy. We assessed the frequency of esophageal perforation after endoscopic procedures in a highly specialized endoscopy unit and compared clinical outcomes in patients undergoing either surgical or conservative management. METHODS From January 1985 to June 1996, 1011 instrumental endoscopic procedures (dilatation and bougienage) were performed in our department. The computerized complication database was searched to identify all patients with esophageal perforation during this same period, and their records were reviewed. RESULTS Seventeen esophageal perforations (1.7%) occurred in the course of 1011 procedures. Four perforations resulted from balloon dilatation, and 13 were secondary to bougienage. Six patients were managed surgically (35%), all of them recovering uneventfully. Eleven patients were managed conservatively, mainly because they were unfit for surgery. Survival rate in this group was 82%; only two patients died, both of whom had underlying malignant disease. CONCLUSIONS The current concept in management of esophageal perforations comprises surgical as well as medical treatment. In well-selected cases, non-operative treatment can be considered with favorable results.

Cure with omeprazole plus amoxicillin versus long-term ranitidine therapy in Helicobacter pylori–associated peptic ulcer bleeding☆☆☆★★★

BACKGROUND Long-term prophylaxis with ranitidine reduces the risk of recurrent bleeding in patients with a history of bleeding peptic ulcers. To date, no randomized study has been performed to compare cure of Helicobacter pylori infection versus H2 blocker prophylaxis in patients with bleeding peptic ulcer. METHODS In a prospective randomized study, 95 consecutive patients with H. pylori-associated peptic ulcer bleeding were randomized to either ranitidine prophylaxis (150 mg at night) for 2 years or to H. pylori-eradication with omeprazole 60 mg twice daily plus amoxicillin 750 mg three times daily for 10 days. RESULTS (Intention-to-treat analysis). Forty-eight patients were enrolled in the ranitidine group; 47 in the omeprazole-plus-amoxicillin group. Mean follow-up was 576 days (77 to 730). Ulcer recurrence rate was 31.3% in the ranitidine group (group 1) versus 6.37% in the eradication group (group 2; p = 0.0018). More patients had recurrent bleeding in group 1 (8.3%) than in group 2 (4.2%) but we were not able to show a statistically significant difference with respect to recurrent bleeding between groups (p = 0.29). Definite cure of H. pylori infection was achieved in 89.3%. CONCLUSIONS Cure of H. pylori infection reduces recurrence of peptic ulcer and therefore rebleeding more effectively than does long-term maintenance therapy with an H2 blocker.