Peter B. Kelsey

A randomized trial comparing uncovered and partially covered self- expandable metal stents in the palliation of distal malignant biliary obstruction

BACKGROUND The most common complication of uncovered biliary self-expandable metal stents (SEMSs) is tumor ingrowth. The addition of an impenetrable covering may prolong stent patency. OBJECTIVE To compare stent patency between uncovered and partially covered SEMSs in malignant biliary obstruction. DESIGN Multicenter randomized trial. SETTING Four teaching hospitals. PATIENTS Adults with inoperable distal malignant biliary obstruction. INTERVENTIONS Uncovered or partially covered SEMS insertion. MAIN OUTCOME MEASURES Time to recurrent biliary obstruction, patient survival, serious adverse events, and mechanism of recurrent biliary obstruction. RESULTS From October 2002 to May 2008, 129 patients were randomized. Recurrent biliary obstruction was observed in 11 of 61 uncovered SEMSs (18%) and 20 of 68 partially covered SEMSs (29%). The median times to recurrent biliary obstruction were 711 days and 357 days for the uncovered and partially covered SEMS groups, respectively (P = .530). Median patient survival was 239 days for the uncovered SEMS and 227 days for the partially covered SEMS groups (P = .997). Serious adverse events occurred in 27 (44%) and 42 (62%) patients in the uncovered and partially covered SEMS groups, respectively (P = .046). None of the uncovered and 8 (12%) of the partially covered SEMSs migrated (P = .0061). LIMITATIONS Intended sample size was not reached. Allocation to treatment groups was unequal. CONCLUSIONS There was no significant difference in time to recurrent biliary obstruction or patient survival between the partially covered and uncovered SEMS groups. Partially covered SEMSs were associated with more serious adverse events, particularly migration.

Cytomegalovirus- and Cryptosporidium-associated acalculous gangrenous cholecystitis

A well-documented case of cytomegalovirus- and Cryptosporidium-associated cholecystitis is described in a 19-year-old heterosexual Haitian man who had the acquired immune deficiency syndrome and acute acalculous gangrenous cholecystitis associated with these pathogens. This case adds to the spectrum of the manifestations of the profoundly immunocompromised state.

Mutation mapping and identification by whole genome sequencing

Genetic mapping of mutations in model systems has facilitated the identification of genes contributing to fundamental biological processes including human diseases. However, this approach has historically required the prior characterization of informative markers. Here we report a fast and cost-effective method for genetic mapping using next-generation sequencing that combines single nucleotide polymorphism discovery, mutation localization, and potential identification of causal sequence variants. In contrast to prior approaches, we have developed a hidden Markov model to narrowly define the mutation area by inferring recombination breakpoints of chromosomes in the mutant pool. In addition, we created an interactive online software resource to facilitate automated analysis of sequencing data and demonstrate its utility in the zebrafish and mouse models. Our novel methodology and online tools will make next-generation sequencing an easily applicable resource for mutation mapping in all model systems.

Successful Treatment of Nonhealing Biliar-Cutaneous Fistulas With Biliary Stents

Biliary-cutaneous fistulas occasionally complicate biliary tract surgery. Distal biliary obstruction, extensive loss of bile duct wall, or infection may contribute to the failure of such fistulas to heal. Five cases are reported of high-volume persistent fistulas that healed promptly after placement of endoscopic (4 cases) or percutaneous (1 case) biliary stents. Biliary stent placement eliminated the need for difficult reoperations in these complex patients and offers a promising therapeutic approach to this problem.

Embolization of an hepatic artery pseudoaneurysm following laparoscopic cholecystectomy.

Vascular injuries during laparoscopic cholecystectomy can occur in an analogous fashion to biliary injuries, with potential laceration, transection, and occlusion of blood vessels. A patient presented with symptomatic hemobilia 1 month following laparoscopic cholecystectomy and was found to have a right hepatic artery pseudoaneurysm which communicated with the common bile duct. This was successfully embolized with several embolic agents, resulting in rapid resolution of all signs and symptoms. The patient has been free of symptoms during a follow-up period of 1 year. A brief discussion of hepatic artery pseudoaneurysms is presented.

Rargb regulates organ laterality in a zebrafish model of right atrial isomerism.

Developmental signals determine organ morphology and position during embryogenesis. To discover novel modifiers of liver development, we performed a chemical genetic screen in zebrafish and identified retinoic acid as a positive regulator of hepatogenesis. Knockdown of the four RA receptors revealed that all receptors affect liver formation, however specific receptors exert differential effects. Rargb knockdown results in bilateral livers but does not impact organ size, revealing a unique role for Rargb in conferring left-right positional information. Bilateral populations of hepatoblasts are detectable in rargb morphants, indicating Rargb acts during hepatic specification to position the liver, and primitive endoderm is competent to form liver on both sides. Hearts remain at the midline and gut looping is perturbed in rargb morphants, suggesting Rargb affects lateral plate mesoderm migration. Overexpression of Bmp during somitogenesis similarly results in bilateral livers and midline hearts, and inhibition of Bmp signaling rescues the rargb morphant phenotype, indicating Rargb functions upstream of Bmp to regulate organ sidedness. Loss of rargb causes biliary and organ laterality defects as well as asplenia, paralleling symptoms of the human condition right atrial isomerism. Our findings uncover a novel role for RA in regulating organ laterality and provide an animal model of one form of human heterotaxia.

Endoscopic palliation of obstructive esophagogastric malignancy

To investigate the efficacy of alternative endoscopic palliative therapies for obstructive esophagogastric malignancy, the experience of 53 patients treated between 1979 and 1986 was analyzed. Forty-seven patients had placement of intraesophageal prostheses. Ten patients had prostheses placed after neodymium:YAG laser therapy. In four of these patients, prosthesis placement was planned as part of the initial therapy. Twelve patients initially received laser therapy. In six, recurrent tumor was treated with intraesophageal prostheses 3 to 24 weeks after laser treatment. Comparing neodymium:YAG laser therapy to placement of the prosthesis, both techniques provided similar improvement in dysphagia. Patients receiving prostheses required less additional treatment for dysphagia. Life table analysis comparing survival rates from diagnosis to death showed no difference. The palliation provided by prostheses and neodymium:YAG laser appears to be quite similar; however, the prosthesis seems to be more lasting and require fewer resources.

Adverse Event and Complication Management in Gastrointestinal Endoscopy

Gastrointestinal endoscopy is a remarkably safe set of diagnostic and therapeutic techniques, and yet a small number of significant complications and adverse events are expected. Serious complications may have a material effect on the patient’s health and well-being. They need to be anticipated and prevented if possible and managed effectively when identified. When complications occur they need to be discussed frankly with patients and their families. Informed consent, prevention, early detection, reporting, and systems improvement are critical aspects of effective complication management. Optimal complication management may improve patient satisfaction and outcome, as well as preserving the reputation and confidence of the endoscopist, and may minimize litigation.

Duodenoscope assisted cholangiopancreatoscopy: a review of clinical applications.

Duodenoscope assisted cholangiopancreatoscopy allows direct visualization of the pancreatic duct and bile duct. There are several circumstances where direct ductal visualization might be helpful in clarifying a diagnosis or providing targeted treatment. Duodenoscope assisted cholangiopancreatoscopy is currently employed for a variety of indications including: indeterminate ductal strictures and filling defects, marginal chronic pancreatitis, treatment of large intraductal stones, localization of intraductal papillary mucinous tumors, and localization and treatment of hemobilia. There have however been no randomized controlled trials evaluating the diagnostic or therapeutic functions of duodenoscope assisted cholangiopancreatoscopy. This article reviews recent descriptive studies that attempt to clarify the clinical role of this technology.

Medical device evaluation by the Food and Drug Administration (FDA).

VOLUME 53, NO. 7, 200