Safety and feasibility of single use cholecystoscopy for guiding laser or mechanical cholelithotripsy,and mechanical cholelithotomy

PURPOSEPatients with acute calculus cholecystitis and contraindications to cholecystectomy receive cholecystostomy drainage catheters, many of which remain in place until end of life. This study aims to assess safety, feasibility, and early clinical outcomes of percutaneous cholecystoscopy using the LithoVue endoscope, laser/mechanical cholelithotripsy, and mechanical cholelithotomy for management of symptomatic cholelithiasis.METHODSThis was a single-institute retrospective analysis of 17 patients with acute calculus cholecystitis who had contraindications to cholecystectomy, underwent cholecystostomy catheter placement between 2015 and 2017, and stone removal between 2017 and 2018. The LithoVue 7.7-9.5 F endoscope was used in combination with laser/mechanical cholelithotripsy, mechanical retrograde, and balloon-assisted anterograde cholelithotomy to remove gallstones and common bile duct stones. Surgical contraindications ranged from cardiopulmonary disease to morbid obesity to neoplastic processes. Timing and number of interventions, as well as technical and clinical successes, were assessed.RESULTSThe median time interval from cholecystostomy catheter placement to cholelithotripsy was 58 days, after an average of 2 tube exchange procedures. Technical and clinical success were achieved in all patients (stone-free gallbladder and cholecystostomy tube removal). On average, three sessions of cholecystoscopy and laser and mechanical cholelithotripsy were required for complete gallstone extraction. The mean interval time between the first cholelithotripsy session and removal of cholecystostomy was 71.8 ± 60.8 days. There were neither major nor minor procedure-related complications.CONCLUSIONPercutaneous cholecystoscopy using the LithoVue endoscope, in combination with laser/mechanical cholelithotripsy and mechanical cholelithotomy, is feasible, safe, well-tolerated, and was able to remove the cholecystostomy tube in the patients with contraindication to cholecystectomy.

Main points

• Percutaneous cholecystoscopy using the LithoVue endoscope is safe and effective in patients with acute cholecystitis that are poor surgical candidates.
• Laser/mechanical cholelithotripsy and mechanical retrograde/anterograde cholelithotomy are well tolerated using existing cholecystostomy access.
• Cholelithotripsy and cholelithotomy with percutaneous cholecystoscopy can play a role in eventual cholecystostomy tube removal.

Cholelithiasis is a common condition in the Western world, affecting 10%-15% of the population. Of those with the signs and symptoms of biliary colic, 20% experience acute calculous cholecystitis.¹ Although cholecystectomy is the standard of care for acute calculous cholecystitis, percutaneous cholecystostomy placement is considered as first-line treatment in critically ill patients and patients with multiple comorbidities or otherwise poor operative candidates.² Cholecystostomy tubes typically remain in place until the gallbladder is removed or the stones are removed, assuming the cystic duct and common bile duct (CBD) are patent. Otherwise, obstruction may reoccur after drain removal in more than 33% of patients with untreated cholelithiasis.³ Therefore, many of cholecystostomy patients live with the tube for life and are referred to interventional radiologist for cholecystostomy tube maintenance every 2-3 months, primarily to maintain catheter patency.Various approaches have been developed or attempted for nonsurgical gallbladder stone removal ranging from chemical dissolution to extracorporeal shock wave lithotripsy, mechanical, electrohydraulic, ultrasonic or laser lithotripsy, and basket extraction. Recent studies have evaluated direct visualization to aid biliary intervention using endoscopic techniques, with one study using the LithoVue (Boston Scientific), a disposable digital flexible scope originally developed to access the upper urinary tract.^4,5 However, only a few studies have reported management of symptomatic cholelithiasis using percutaneous cholecystoscopy, with technical success rates of around 95% and recurrent cholelithiasis recurrent rate of less than 5%.^6-10The aim of this study is to evaluate safety and feasibility of the LithoVue endoscope for diagnostic evaluation and direct visualization during cholelithotripsy and cholelithotomy of the gallbladder, cystic, and CBD, and finally examine effectiveness of the procedure in removing cholecystostomy in these patients.     

Detection of visual field progression in glaucoma with standard achromatic perimetry: A review and practical implications

Detection of visual field progression remains a challenging task despite the recent advances for better handling of longitudinal visual field data, some of which are incorporated in currently available perimeters. Standard achromatic perimetry remains the gold standard for detection of visual field progression. The authors present a practical and clinically relevant review of the main issues involved in detection of early glaucoma as well as detection of visual field progression in eyes with pre-existing glaucomatous damage. After discussing some basic concepts in perimetry, the authors present evidence-based recommendations for criteria to detect earliest evidence of glaucomatous damage with perimetry. The authors will review different event- and trend-based criteria and present data with regard to comparative performance of such criteria. Relevance of using absolute versus corrected threshold data with regard to different criteria is also addressed. At the end, the authors provide practical guidelines for detection of visual field progression in a clinical setting and review issues related to clinical trials.     

Ultrastructural and Electron Energy Loss Spectroscopy Studies of Sequestration Mechanisms of Cd and Cu in the Marine Diatom Skeletonema costatum

The marine diatom Skeletonema costatum was used to study mechanisms of detoxification when submitted to cadmium and copper contamination. After 96 h of growth, concentration corresponding to 50% growth inhibition (IC₅₀, 96 h) was 0.224 mg/L for cadmium and 0.045 mg/L for copper, indicating that copper is more toxic for S. costatum than cadmium. Heavy cellular damages were observed for cadmium and copper concentrations close to the IC₅₀. Exposure to these concentrations induced a migration of inclusions from the peripheral cytoplasm to the vacuole. Electron energy loss spectroscopy (EELS) investigations demonstrated that Cd and Cu were specifically trapped in these inclusions. However, Cu was less sequestered than cadmium in the vacuole. EELS determination of oxidation states evidenced that trace metals were sequestered as Cd²⁺ and Cu²⁺. Nitrogen and sulfur are involved in metallic storage, especially in the case of cadmium contamination. Received: 6 August 1996/Revised: 18 February 1997     

A general practice survey of the incidence ofMycoplasma pneumoniae infections

An epidemiological survey was carried out at two centres in the north of England (Liverpool and Sunderland). One hundred and twenty patients were included in this survey to determine the relative incidence ofMycoplasma pneumoniae infections in patients who present to their physician with an acute lower respiratory tract infection. Data were available at the end of the survey in 115 patients. Only one patient had a positive test forM. pneumoniae. There were nine patients who had a positive antibody test for either influenza or para-influenza. Four patients had a positive test for respiratory syncytial viruses. This survey points out the problems in the clinical diagnosis of respiratory infections in general practice.     

Synthesis, antiproliferative, and antiviral activity of certain 4-substituted and 4,5-disubstituted 7-[(1,3-dihydroxy-2-propoxy)methyl]pyrrolo[2,3-d]pyrimidines

The sodium salts of 4-chloro- and several 4-chloro-5-substituted-7H-pyrrolo[2,3-d]pyrimidines were treated with [1,3-bis(benzyloxy)-2-propoxy]methyl chloride (6) to provide the corresponding 4-chloro- and 4-chloro-5-substituted-7-[[1,3-bis(benzyloxy)-2-propoxy]methyl]pyrrolo [2,3-d]pyrimidines (7-11). Debenzylation with boron trichloride at -78 degrees C furnished 4-chloro- and several 4-chloro-5-substituted-7-[(1,3-dihydroxy-2-propoxy)methyl]pyrrolo[2,3- d]pyrimidines (12.16). Subsequent amination of 12-16 yielded the 4-amino-5-substituted-7-[(1,3-dihydroxy-2-propoxy)methyl]pyrrolo[2,3- d]pyrimidines (17-21). Treatment of 14 with methylamine and 13 and 14 with ethylamine yielded the 4-(alkylamino)-5-halo-7-[(1,3-dihydroxy-2- propoxy)methyl]pyrrolo[2,3-d]pyrimidines (22-24). Treatment of 12-15 with hydroxylamine in refluxing 2-propanol yielded the 5-substituted-4-(hydroxyamino)-7-[(1,3-dihydroxy-2-propoxy)methyl]pyrrol o [2,3-d]pyrimidines (25-28). Treatment of compound 12 with Pd/C under a hydrogen atmosphere has furnished the nebularine analogue 31. The antiproliferative activity of compounds 17-28 and 31 was studied using L1210 cells in vitro. The 4-amino- and 4-(hydroxyamino)-5-halogenated derivatives (compounds 18-20, 26-28) inhibited cell growth. Although the effect of compounds 18-20 and 27 on final growth rate was pronounced (IC50 = 2.3, 0.7, 2.8, and 3.7 microM, respectively), cells underwent at least one doubling before cell division stopped. The remaining compounds were less cytotoxic, with IC50's greater than 30 microM for 21, 23, 26, and 28, whereas no inhibition of L1210 cell growth was observed with compounds 17, 22, 24, 25, and 31 at 100 microM. The antiviral activity of these compounds also was tested. Compounds 18-20 and 26-28 were active against human cytomegalovirus and herpes simplex type 1. The 4-amino derivatives (18-20) were more active than the 4-hydroxyamino derivatives (26-28), the 4-amino-5-bromo and 4-amino-5-iodo derivatives produced more than five log reductions in virus titer at concentrations of 10-100 microM. Although some cytotoxicity was observed at these concentrations, compound 19 was active against murine cytomegalovirus in vivo. At 5.6 mg/kg, 14/15 animals survived compared to 10/15 treated with 5.6 mg/kg of ganciclovir or 1/15 treated with placebo.     

The diaphragmatic echo complex: an in vitro study

The brightly echogenic appearance of the diaphragm on routine clinical scans is not easily reconciled with the well-documented echo-poor appearance of muscle elsewhere in the body. A series of specimens of normal human diaphragm freshly excised at autopsy were suspended in a water bath. Articulated arm scans were done varying the angle of the incident beam to the specimen by 5-degree increments and recording the maximum attenuation which allowed visualization (ie, an extinction point). This was accomplished for intact diaphragm, peritoneal membrane alone, and diaphragmatic muscle alone with both membranes stripped. The bright specular echoes seen are due almost exclusively to the membranes (parietal pleura and peritoneum) and the diaphragmatic muscle itself produces only low-level scattered echoes as elsewhere. However, these scattered echoes account for persistent visualization of the diaphragm at steep angles of the incident beam. A considerable portion of the in vivo thickness of the diaphragmatic echo complex is, therefore, produced by diaphragm-lung interface.     

Synthesis and antiviral activity of certain 4- and 4,5-disubstituted 7-[(2-hydroxyethoxy)methyl]pyrrolo[2,3-d]pyrimidines

In vitro evaluation of a series of previously prepared tubercidin analogues revealed that certain 5-halogen-substituted analogues were active against human cytomegalovirus (HCMV) at concentrations lower than those that produced comparable cytotoxicity in uninfected cells. In contrast, tubercidin was cytotoxic at all antiviral concentrations. Even though the antiviral selectivity of the 5-substituted compounds was slight, this observation led us to prepare a series of acyclic analogues. Treatment of the sodium salt of 4-chloropyrrolo[2,3-d]pyrimidine (2) with (2-acetoxyethoxy)methyl bromide (2a) provided the acyclic nucleoside 4-chloro-7-[(2-acetoxyethoxy)methyl]pyrrolo[2,3-d]pyrimidine (3). A nucleophilic displacement of the 4-chloro group with methoxide, methylamine, and dimethylamine yielded the corresponding 4-substituted compounds 4, 5, and 6, respectively, in good yield. Electrophilic substitution (chlorination, bromination, and iodination) was effected at the C-5 position of compound 3 with N-chlorosuccinimide, N-bromosuccinimide, and iodine monochloride, respectively, in methylene chloride. Removal of the acetyl group from these intermediates (7a-9a) with methanolic ammonia at room temperature afforded the 5-chloro (7b), 5-bromo (8b), and 5-iodo (9b) derivatives of 4-chloro-7-[(2-hydroxyethoxy)methyl]pyrrolo[2,3-d]pyrimidine. Treatment of compounds 7b-9b with methanolic ammonia at an elevated temperature produced the corresponding 5-halotubercidin analogues 10, 11, and 12, respectively. An alternate procedure for the preparation of these 4,5-disubstituted 7-[(2-hydroxyethoxy)methyl]pyrrolo[2,3-d]pyrimidines involved an electrophilic substitution prior to the condensation of the heterocycle with 2a. Treatment of 2 with N-chlorosuccinimide and N-bromosuccinimide gave compounds 13a and 13b, respectively. The condensation of 13a and 13b with 2a and subsequent treatment with methylamine and ethylamine furnished the corresponding 5-halo-4-substituted-pyrrolo[2,3-d]pyrimidines 14a, 14b, 14c, and 14d, respectively. Evaluation of the target compounds (4-6, 7b-9b, 10-12, and 14a-14d) for cytotoxicity and activity against HCMV and herpes simplex virus type 1 (HSV-1) revealed that all compounds except the 5-halogen-substituted compounds 10, 11, and 12 were inactive. Compounds 10, 11, and 12 were active against both viruses at noncytotoxic concentrations. The activity of compound 11 was particularly noteworthy, being at least 10-fold more potent than acyclovir.     

Tissue detection of biomolecular predictors in breast cancer

One of the promises of modern biotechnology is to improve medical care by providing accurate diagnosis and targeted treatment to patients who will derive the maximum benefit. Delivery of this promise in the 21st century is the result of major advances in biotechnology over the past 20 years. Sequencing of the human genome and other high-volume data discovery has become possible, owing to relatively inexpensive computation power and automation. The same forces that drove the human genome project are now being focused on cataloging various disease processes at the DNA, RNA and protein levels. As these high-throughput technologies are entering the clinical care environment, the major task at hand is to integrate the complex data and derive clinically useful information. In spite of major breakthroughs in molecular approaches to the diagnosis and prognostication of cancer, there remain significant obstacles in applying these technologies to clinical samples. The time-honored conventional histopathology, for example, is still the backbone of tumor diagnosis and prognostication. The traditional fixation and processing methods are, however, rapidly losing ground, as they do not protect important tissue macromolecules. Formalin, the common universal fixative, is losing its place in histopathology. In addition to its toxicity, it alters macromolecules and renders the tissue unfit for most advanced molecular studies. This has prompted the use of fresh or fresh-frozen biopsy material for most biomolecular discoveries and clinical assays. This of course is impractical, or even impossible, in most clinical settings, particularly since tumors are being detected earlier and smaller. Also, many preneoplastic conditions are impossible to triage for freezing since their accurate diagnosis requires the use of the entire sample for detailed microscopic examination. The focus in this report is on breast cancer, where the value of the innovative approaches of the tissue detection of biomolecular predictors is examined. To this end, novel tissue handling platforms are introduced that are not only suitable for histological diagnosis, but allow the detection of tumor proteome and expression profiles on the same biopsy sample.