Comparison of in vivo probe-based confocal laser endomicroscopy with histopathology in lung cancer: A move toward optical biopsy.

BACKGROUND AND OBJECTIVE: The development of novel technologies has increased the yield from transbronchial biopsies while preserving patient safety by guiding biopsies to the area of interest. Other technologies have helped identify pre-cancerous or sessile lesions in the endobronchial space by utilizing interactions between tissue and light at varying wavelengths. Probe-based confocal laser endomicroscopy (pCLE) is a new technology that encompasses the benefits of both guided biopsies and novel optical imaging in one device. This project compares pCLE images to the findings of light microscopy in non-small cell lung cancer (NSCLC). METHODS: Patients who underwent bronchoscopies between July 2012 and January 2013 for evaluation of pulmonary lesions (transbronchial and endobronchial) were recruited. Histopathological images from malignant lesions were compared with the pCLE images obtained from the same area. The microscopic and pCLE images were reviewed side by side with the microscopic findings. RESULTS: Images from pCLE correlate with some histopathological findings. pCLE changes seen in NSCLC consist of mottled elastin, septal studding and disorganization/fragmentation with increased friability. These changes also seem to correlate with degrees of differentiation. CONCLUSIONS: pCLE can identify changes to the elastin composition of the airways and alveoli in lung cancer. These changes correlate with histopathology and may help indicate the presence of malignant changes in vivo.

Airway spray cryotherapy: initial outcomes from a multiinstitutional registry.

BACKGROUND: Spray cryotherapy (SCT) uses a noncontact system to deliver liquid nitrogen (2 to 4 psi) through an endoscopic catheter. Rapid freezing and thawing of tissue causes cellular death and is also hemostatic. We report the preliminary results from 6 institutions in which SCT was used for the treatment of malignant airway tumors. METHODS: SCT was performed on patients with symptomatic airway tumors and reviewed retrospectively. Airway narrowing was graded as 25% or smaller, 26% to 50%, 51% to 75%, and exceeding 75%. All events were documented and assessed. RESULTS: Eighty patients (45 male [56%]) underwent 114 treatments. Median age was 66 years (range, 15 to 90 years). All patients were treated with minimal blood loss. Fifty-eight percent of the cases were outpatient procedures. Airway obstruction exceeded 75% in most of the lesions treated. There were 21 intraoperative events (19%), including hypotension, bradycardia and tachycardia, ST segment changes, desaturation, and an airway tear. Three pneumothoraces occurred, one requiring emergency chest tube placement. Two intraoperative deaths were associated with bradycardia. Three postoperative deaths occurred in patients who were transitioned to comfort care. All but 1 patient had airway patency after treatment. CONCLUSIONS: SCT can be used in patients with highly vascular tumors, with reduced bleeding complications and a low overall complication rate. Caution is needed before SCT is used on a widespread basis, given the intraoperative complications. Although the potential benefit of SCT is considerable, this needs to be confirmed in larger studies.

Photodynamic therapy (PDT) for lung cancer.

Clinical PDT began in the early 1980s and lung cancer was one of the first indications for which the procedure was tried. Initially patients with advanced inoperable cancer and major bronchial obstruction were targeted with the objective of relief of airway obstruction and symptom palliation. In the past 30 years, assisted by progress in imaging methods and advances of technological developments, PDT indications have expanded to incorporate a multitude of lung cancer presentations which this review aims to display. Locally advanced and early stage endobronchial cancer continues to be the major indications albeit with a more precise diagnostic and guided illumination devices. Peripheral parenchymal disease has been a technical challenge but there is still ongoing development. Multifocal synchronous, recurrence and metachronous endobronchial disease following lung resection are now an up and coming indication with rewarding outcome. More importantly PDTs role within a multi-disciplinary assault on lung cancer is receiving acceptance.

False extended-spectrum {beta}-lactamase phenotype in clinical isolates of Escherichia coli associated with increased expression of OXA-1 or TEM-1 penicillinases and loss of porins.

OBJECTIVES: Two clinical isolates of Escherichia coli, EC18 and EC21, were non-susceptible (MICs 4-16 mg/L) to cefpirome and cefepime, with marked synergy with clavulanate, yet were susceptible to cefotaxime and ceftazidime (MICs ≤ 1 mg/L). EC19, from the same patient as EC21, was susceptible to all four cephalosporins. We sought to characterize the molecular basis of resistance in isolates EC18 and EC21. METHODS: PFGE was used to study the genetic relationships of the isolates, and MICs were determined. ß-Lactamases were characterized by PCR, isoelectric focusing (IEF), construction of genomic libraries and sequencing. A double mutant of E. coli J53 was constructed, lacking OmpC and OmpF porins. Plasmids from clinical isolates were transformed into E. coli J53 and J53ΔompCF. Outer membrane proteins (OMPs) were analysed by SDS-PAGE and OmpA by matrix-assisted laser desorption ionization time-of-flight/time-of-flight mass spectrometry. Expression of omp and bla genes was analysed by RT-PCR. RESULTS: Isolates EC19 and EC21 had identical PFGE profiles, whereas EC18 was distinct. PCR and IEF confirmed ß-lactamases with pIs of 5.4 (TEM-1) in EC18 and 7.4 (OXA-1) in both EC19 and EC21. EC18 had bla(TEM-1b) with the strong promoter P5 and lacked OmpC and OmpF. RT-PCR showed stronger expression of bla(OXA-1) in EC21 versus EC19, along with diminished expression of OmpC, though with increased OmpF. Plasmids extracted from EC18 and EC21 conferred increased MICs of cefpirome and cefepime, although susceptibility to cefotaxime and ceftazidime was retained. CONCLUSIONS: The 'cefpiromase' or 'cefepimase' ESBL phenotype of the clinical isolates non-susceptible to cefpirome and cefepime resulted from high expression of TEM-1 or OXA-1 ß-lactamases combined with loss of porins.

Feasibility of spray cryotherapy and balloon dilation for non-malignant strictures of the airway.

OBJECTIVE: Benign airway strictures can be complex and challenging to manage. Although resection is preferred, this is not always feasible, and hence, endoscopic therapies are often performed. However, endoscopic therapies can be problematic, with granulation tissue and fibrosis leading to early failure. Spray cryotherapy (SC) is a new approach that may modulate the healing response leading to less fibrosis and decrease the need or the duration of time to intervention. We report the initial results of SC for benign airway strictures. METHODS: Over a 22-month period, 35 patients underwent SC. Median age was 51(18-81) years. Prior therapy had been undertaken in 14 (41.2%) of patients. Stricture etiology included post intubation (n=5), prior tracheostomy (n=6), radiation induced (n=2), prior surgery (n=3), other causes (n=12), or unknown etiology (n=7). Airway narrowing was graded as follows: 1=0-25%, 2=26-50%, 3=51-75%, and 4=76-100%. For the purpose of analysis, this was treated as a continuous variable. The usual treatment algorithm consisted of ×3-4 SC cycles, followed by balloon dilation, and then by additional SC cycles. RESULTS: Stricture locations were subglottic (n=18), tracheal (n=9), and bronchial (n=8). Seventeen (49%) patients required additional SC therapy, resulting in a total of 63 SC treatment sessions. Only two (3.2%) complications occurred and these included pneumothorax (n=1) and intra-operative tracheostomy (n=1). Mean follow-up was available in 33/35 patients at a mean of 8.2 (1-19) months. Twelve (of 33) patients (36.4%) were asymptomatic, 16/33 (48.5%) were improved, 4/33(12.1%) had no improvement or were worse, and 1/33(3%) patient died from an unrelated cancer. On follow-up bronchoscopy, performed in 28 patients, airway narrowing improved significantly from 3.5 to 2.03 (p<0.001). CONCLUSIONS: Initial experience with SC for benign airway strictures suggests that this can be used safely. This is effective in improving symptoms and reducing the severity of airway narrowing. Re-intervention is still required. Further study should be undertaken to determine factors that may be associated with success or failure as well as the relative efficacy of SC compared with other endoscopic therapies.

Results of combined photodynamic therapy (PDT) and high dose rate brachytherapy (HDR) in treatment of obstructive endobronchial non-small cell lung cancer (NSCLC).

INTRODUCTION: We reviewed the outcome of combined photodynamic therapy (PDT) and high dose rate brachytherapy (HDR) for patients with symptomatic obstruction from endobronchial non-small cell lung cancer. METHODS: Nine patients who received combined PDT and HDR for endobronchial cancers were identified and their charts reviewed. The patients were eight males and one female aged 52-73 at diagnosis, initially presenting with various stages of disease: stage IA (N=1), stage IIA (N=1), stage III (N=6), and stage IV (N=1). Intervention was with HDR (500 cGy to 5 mm once weekly for 3 weeks) and PDT (2 mg/kg Photofrin, followed by 200 J/cm(2) illumination 48 h post-infusion). Treatment group 1 (TG-1, N=7) received HDR first; Treatment group 2 (TG-2, N=2) received PDT first. Patients were followed by regular bronchoscopies. RESULTS: Treatments were well tolerated, all patients completed therapy, and none were lost to follow-up. In TG-1, local tumor control was achieved in six of seven patients for: 3 months (until death), 15 months, 2+ years (until death), 2+ years (ongoing), and 5+ years (ongoing, N=2). In TG-2, local control was achieved in only one patient, for 84 days. Morbidities included: soft-tissue contraction and/or other reversible benign local tissue reactions (N=8) and photosensitivity reactions (N=2). CONCLUSIONS: Combined HDR/PDT treatment for endobronchial tumors is well tolerated and can achieve prolonged local control with acceptable morbidity when PDT follows HDR and when the spacing between treatments is 1 month or less. This treatment regimen should be studied in a larger patient population.

A prospective multicenter study of competency metrics and educational interventions in the learning of bronchoscopy among new pulmonary fellows.

BACKGROUND: Learning medical procedures relies predominantly on the apprenticeship model, and competency is established based on the number of performed procedures. Our study aimed to establish bronchoscopy competency metrics based on performance and enhanced learning with educational interventions. METHODS: We conducted a prospective study of the acquisition of bronchoscopy skills and cognitive knowledge in two successive cohorts of new pulmonary fellows between July 5, 2006, and June 30, 2008. At prespecified milestones, validated tools were used for testing: the Bronchoscopy Skills and Tasks Assessment Tool (BSTAT), an objective evaluation of bronchoscopy skills with scores ranging from 0 to 24, and written multiple-choice questions examinations. The first cohort received training in bronchoscopy as per the standards set by each institution, whereas the second cohort received educational interventions, including training in simulation bronchoscopy and an online bronchoscopy curriculum. RESULTS: There was significant variation among study participants in bronchoscopy skills at their 50th bronchoscopy, the minimum number previously set to achieve competency in bronchoscopy. An educational intervention of incorporating simulation bronchoscopy enhanced the speed of acquisition of bronchoscopy skills, as shown by the statistically significant improvement in mean BSTAT scores for seven of the eight milestone bronchoscopies (P < .05). The online curriculum did not improve the performance on the written tests; however, compliance of the learners with the curriculum was low. CONCLUSIONS: Performance-based competency metrics can be used to evaluate bronchoscopy skills. Educational interventions, such as simulation-based training, accelerated the acquisition of bronchoscopy skills among first-year pulmonary fellows as assessed by a validated objective assessment tool.

Response to spray cryotherapy in a patient with adenocarcinoma in the parietal pleura.

Malignancies of the parietal pleura, whether primary or metastatic, are a therapeutic challenge, and current therapies target their symptoms and not their tumor burden. Therefore, alternatives to standard approaches seem warranted. A patient with a parietal pleura-based adenocarcinoma was treated with low-pressure spray cryotherapy after failing more traditional approaches. The patient underwent therapeutic pleuroscopy with moderate sedation and local analgesia of the right chest. She was treated with the CSA Medical spray cryotherapy system, which was introduced into the chest via the working channel of a semi-rigid pleuroscope. Pleuroscopic examination 3 days after spray cryotherapy revealed >50% reduction in tumor size. No adverse events or complications occurred as a result of treatment. At the 3-month follow-up, a slightly raised mound of tissue was noted at the treatment site. This area was biopsied and found to be negative for tumor, containing only chronic inflammatory tissue. No evidence of residual cancer was observed. Initial observations include lack of a bystander effect on lung and pleura; no significant side effects or symptoms; a 50% tumoricidal response 3 days after treatment, and a complete tumoricidal response 90 days after treatment without evidence of tumor on the parietal pleura.

A phase 3, randomized, double-blind study to assess the efficacy and safety of fospropofol disodium injection for moderate sedation in patients undergoing flexible bronchoscopy.

BACKGROUND: Fospropofol disodium is a water-soluble prodrug of propofol with unique pharmacokinetic/pharmacodynamic properties. This randomized, double-blind, multicenter study evaluated the use of fospropofol in patients undergoing flexible bronchoscopy. METHODS: Patients >or= 18 years of age were randomized (2:3) to receive fospropofol, 2 mg/kg or 6.5 mg/kg, after pretreatment with fentanyl, 50 microg. Supplemental doses of each were given per protocol. The primary end point was sedation success, which was defined as follows: three consecutive Modified Observer's Assessment of Alertness/Sedation scores of

Xanthomatous pleuritis mimicking mesothelioma.

Recurrent non-malignant exudative effusions remain a diagnostic and potentially management dilemma. Fluid characteristics frequently narrow the differential but fail to offer a definitive diagnosis. Medical thoracoscopy is well tolerated and allows direct visualization and biopsy of pleural processes under conscious sedation. Rarely, macroscopic appearance and even histology may be misleading. We present a case of xanthomatous pleuritis that mimicked early mesothelioma. Our patient was a 69-year-old female with a large left pleural effusion. Her medical history was significant for a recent small pericardial effusion without cardiac dysfunction. Thoracentesis revealed a non-malignant exudative effusion. Thoracoscopy demonstrated two foci of raised soft plaques with petechial hemorrhage and adhesions. Preliminary evaluation suggested chronic inflammation admixed with proliferating spindle cells and necrosis. The immunohistochemical phenotype of the spindle cells favored a spindle and epithelioid cell neoplasm, mesothelioma. Because of discord between pathologists, we repeated the thoracoscopy through the existing chest tube/thoracoscopy site. We acquired more tissue for special stains and outside review. Following extensive immunohistochemistry, the diagnosis of xanthomatous pleuritis was made. Our patient quickly recovered with steroid therapy and is without recurrence 18 months later. This case demonstrates the utility and nuances of medical thoracoscopy in a perplexing case of xanthomatous pleuritis.

Bronchial intraepithelial neoplasia/early central airways lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition).

BACKGROUND: An evidence-based approach is necessary for the localization and management of intraepithelial and microinvasive non-small cell lung cancer in the central airways. METHODS: Material appropriate to this topic was obtained by literature search of a computerized database. Recommendations were developed by the writing committee and then reviewed by the entire guidelines panel. The final recommendations were made by the Chair and were voted on by the entire committee. RESULTS: White light bronchoscopy has diagnostic limitations in the detection of microinvasive lesions. Autofluorescence bronchoscopy (AFB) is a technique that has been shown to be a sensitive method for detecting these lesions. In patients with moderate dysplasia or worse on sputum cytology and normal chest radiographic findings, bronchoscopy should be performed. If moderate/severe dysplasia or carcinoma in situ (CIS) is detected in the central airways, then bronchoscopic surveillance is recommended. The use of AFB is preferred if available. In a patient being considered for curative endobronchial therapy to treat microinvasive lesions, AFB is useful. A number of endobronchial techniques as therapeutic options are available for the management of CIS and can be recommended to patients with inoperable disease. In patients with operable disease, surgery remains the mainstay of treatment, although patients may be counseled about these techniques. CONCLUSIONS: AFB is a useful tool for the localization of microinvasive neoplasia. A number of endobronchial techniques available for the curative treatment can be considered first-line therapy in inoperable cases. For operable cases, the techniques may be considered and discussed with the patients.

The future of photodynamic therapy in oncology.

The medicinal properties of light-based therapies have been appreciated for millennia. Yet, only in this century have we witnessed the birth of photodynamic therapy (PDT), which over the last few decades has emerged to prominence based on its promising results and clinical simplicity. The fundamental and distinguishing characteristics of PDT are based on the interaction of a photosensitizing agent, which, when activated by light, transfers its energy into an oxygen-dependent reaction. Clinically, this photodynamic reaction is cytotoxic and vasculotoxic. While the current age of PDT is based on oncological therapy, the future of PDT will probably show a significant expansion to non-oncological indications. This harks back to much of the original work from a century ago. Therefore, this paper will attempt to predict the future of PDT, based in part on a review of its origin.

A clinical review of PDT for cutaneous malignancies.

More critical than for most other anatomy, intervention to cutaneous malignancy must not only be therapeutically successful but also achieve excellent cosmetic and functional outcome. As it can achieve those ends, PDT has moved to the forefront in the management of skin cancer. A number of well designed clinical trials and large patient series have reported outstanding outcomes for many histologies. This paper will review the rationale and outcomes of cutaneous PDT to malignancy using both topical and systemic photosensitizers. The benefits and drawbacks of cutaneous PDT are also examined.

Modeling of a type II photofrin-mediated photodynamic therapy process in a heterogeneous tissue phantom.

We present a quantitative framework to model a Type II photodynamic therapy (PDT) process in the time domain in which a set of rate equations are solved to describe molecular reactions. Calculation of steady-state light distributions using a Monte Carlo method in a heterogeneous tissue phantom model demonstrates that the photon density differs significantly in a superficial tumor of only 3 mm thickness. The time dependences of the photosensitizer, oxygen and intracellular unoxidized receptor concentrations were obtained and monotonic decreases in the concentrations of the ground-state photosensitizer and receptor were observed. By defining respective decay times, we quantitatively studied the effects of photon density, drug dose and oxygen concentration on photobleaching and cytotoxicity of a photofrin-mediated PDT process. Comparison of the dependences of the receptor decay time on photon density and drug dose at different concentrations of oxygen clearly shows an oxygen threshold under which the receptor concentration remains constant or PDT exhibits no cytotoxicity. Furthermore, the dependence of the photosensitizer and receptor decay times on the drug dose and photon density suggests the possibility of PDT improvement by maximizing cytotoxicity in a tumor with optimized light and drug doses. We also discuss the utility of this model toward the understanding of clinical PDT treatment of chest wall recurrence of breast carcinoma.

Breast cancer with chest wall progression: treatment with photodynamic therapy.

BACKGROUND: Chest wall progression of breast carcinoma affects up to 5% of breast cancer patients and is a major source of their pain. Treatment options are limited or may not be offered to these patients. Low-dose Photofrin-induced photodynamic therapy (PDT) offers an excellent clinical response with minimal morbidity. We report our continued experience with PDT in this setting. METHODS: Fourteen patients with more than 500 truncal metastases were treated with PDT. All received off-label Photofrin (.8 mg/kg) i.v. and light treatment at 630 nm from a diode laser with a microlens at a fluence of 1800 mW and a total light dose of 150 to 200 J/cm2 at 48 hours. One patient required re-treatment because of extensive disease. RESULTS: Follow-up was at least 6 months, and several extended to >24 months. All patients demonstrated tumor necrosis, with 9 of 14 complete responses, including with lesions >2 cm in thickness. Disease progression occurred outside of the treatment field. Several patients had initial regression of untreated lesions. Wound care, especially with disease in the deep tissues, was an issue. CONCLUSIONS: Low-dose Photofrin-induced PDT offers patients with chest wall progression a treatment option with an excellent clinical response. To date, the response is prolonged and offers good local control. Surgical oncologists have an active role in this treatment option.

Photosensitizers in clinical PDT.

Photosensitizers in photodynamic therapy allow for the transfer and translation of light energy into a type II chemical reaction. In clinical practice, photosensitizers arise from three families-porphyrins, chlorophylls, and dyes. All clinically successful photosensitizers have the ability to a greater or lesser degree, to target specific tissues or their vasculature to achieve ablation. Each photosensitizer needs to reliably activate at a high enough light wavelength useful for therapy. Their ability to fluoresce and visualize the lesion is a bonus. Photosensitizers developed from each family have unique properties that have so far been minimally clinically exploited. This review looks at the potential benefits and consequences of each major photosensitizer that has been tried in a clinical setting.

High-dose-rate brachytherapy in combination with stenting offers a rapid and statistically significant improvement in quality of life for patients with endobronchial recurrence.

Symptomatic endobronchial recurrence after treatment failure is common in advanced non-small cell lung cancer. Optimal palliation has yet to be defined. We examined the combination of near-simultaneous, high-dose-rate (HDR) brachytherapy with stenting in this cohort of patients. Informed consent for intervention was obtained for 10 patients experiencing severely symptomatic (hemoptysis and oxygen-dependent shortness of breath), biopsy-proven endobronchial recurrence. All patients (eight men, two women, aged 52-77 years) had failed to respond to chemoradiotherapy for stage IIIB non-small cell lung cancer. Intervention consisted of placement of a self-expanding metallic stent (Nitinol/Ultraflex stent, Boston Scientific Co., Natick, MA) into the obstructing region. During that same bronchoscopy, HDR catheters were introduced. A dose of 6 Gy at 0.5 cm from the catheter was then delivered via an HDR unit. Two additional HDR sessions followed at weekly intervals for a total dose of 18 Gy. Patients under went follow-up bronchoscopes 1 month after the last HDR and when clinically indicated. All patients completed the prescribed therapy. No morbidity was noted from bronchoscopy, HDR, or stenting. All patients had rapid relief of signs and symptoms. At 1 week after stenting/first HDR, a statistically significant improvement in Karnofsky status was noted. Pulmonary palliation was maintained for the duration of their survival. The radio-opaque stent also offered significant advantages for catheter placement and verification during the HDR procedure. Although this series is small, the beneficial outcome obtained deserves further evaluation.

The use of selective bronchography in predicting reversal of neoplastic obstructive atelectasis.

OBJECTIVES: To assess the ability of selective bronchography to predict which patients with neoplastic postobstructive atelectasis will respond to interventional therapies directed at the reexpansion of the affected lung. Furthermore, to compare the utility of selective bronchography with the current predictive standard that reversal of postobstructive atelectasis is unlikely when it is > or = 4 weeks in duration (ie, the 4-week rule). DESIGN: A prospective observational study. SETTING: A tertiary care referral center/medical school. PATIENTS: Twenty-seven consecutive patients with advanced lung cancer or other malignancy, with documented neoplastic postobstructive atelectasis involving a total of 44 lobes. INTERVENTIONS: Lobar collapse was documented radiographically. The duration of atelectasis was investigated and quantified as accurately as possible. Prior to the use of interventional therapies, selective bronchography was performed on each collapsed lobe, and the results were documented. Bronchography results did not influence the decision to proceed with interventional therapies. Patients had each of their collapsed lobes manipulated by interventional techniques that were directed at reexpansion of the lung. One week after the patient underwent the intervention, the degree of reexpansion was assessed radiographically. RESULTS: Interventional therapies leading to significant reversal of airway narrowing were completed in all 44 lobes. These were successful in reexpanding 28 of 44 collapsed lobes (64%). Selective bronchography demonstrated the following two distinct patterns: an intact bronchial tree (ie, tree pattern); or the absence of a distinguishable, distal bronchial tree (ie, blush pattern). The sensitivity of selective bronchography to predict reexpansion is 1.00 (95% confidence interval [CI], 0.90 to 1.00), and its specificity is 0.56 (95% CI, 0.30 to 0.80). There were no complications attributable to selective bronchography. The sensitivity of the 4-week rule to predict reexpansion is 0.61 (95% CI, 0.41 to 0.78), and its specificity is 0.75 (95% CI, 0.48 to 0.93). The results of selective bronchography and use of the 4-week rule were significantly different in predicting which lobes would reexpand and which would not (p = 0.0026). Using selective bronchography to predict the reversal of lobar atelectasis, the positive predictive value of the tree pattern was 0.80 and the negative predictive value of the blush pattern was 1.00. The values for the 4-week rule are 0.81 and 0.52, respectively. CONCLUSIONS: Selective bronchography is a useful tool for predicting whether patients with neoplastic postobstructive atelectasis would benefit from interventional techniques that are directed at lobar reexpansion. Selective bronchography appears to be superior to the 4-week rule in this regard.

Sickle cell disease, extreme hyperbilirubinemia, and pericardial tamponade: case report and review of the literature.

OBJECTIVE: Sickle cell disease is a relatively common disease seen predominantly in the African-American population with numerous important sequelae that require critical care management. We report a patient who presented with intrahepatic cholestasis, a rare and potentially lethal complication of sickle cell disease. DESIGN: Individual case report and review of the literature. SETTING: Medical intensive care unit of a tertiary care hospital. PATIENT: A 37-yr-old African-American male, with known sickle cell disease, who developed fulminant hepatic failure with subsequent extreme hyperbilirubinemia, coagulopathy, and pericardial tamponade. Additional organ dysfunction included renal insufficiency, respiratory failure, and cardiac dysrhythmias. INTERVENTIONS: The patient underwent serial measurements of complete blood count, hepatic profile, coagulation profiles, and hemoglobin electrophoresis. The patient received exchange transfusion, and his hemoglobin S concentration gradually decreased. Coagulopathy and anemia were corrected with transfusion of fresh frozen plasma and packed red blood cells. Serum bilirubin and other hepatic variables gradually improved. Pericardial tamponade was suggested by right heart catheterization measurements and diagnosed by echocardiographic findings. The tamponade resolved after pericardiocentesis and was managed by drainage through the pericardial catheter. Pulmonary, renal, and cardiac sequelae resolved with intensive supportive care that included intubation, mechanical ventilation, pulmonary artery catheterization, continuous renal replacement therapy, and permanent cardiac pacemaker. The patient was discharged home on hospital day 23 and has not required further hospitalization. CONCLUSION: Sickle cell intrahepatic cholestasis, a potentially fatal complication of sickle cell disease, can present with abdominal pain, acute hepatomegaly, coagulopathy, hyperbilirubinemia, and fulminant hepatic failure. Prompt recognition and early intervention with exchange transfusion and intensive supportive care of multiple organ dysfunction can result in a favorable outcome.