Eastern Canadian Colorectal Cancer Consensus Conference 2017.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2017 was held in St. John's, Newfoundland and Labrador, 28-30 September. Experts in radiation oncology, medical oncology, surgical oncology, and cancer genetics who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics in the management of gastric, rectal, and colon cancer, including ■ identification and management of hereditary gastric and colorectal cancer (crc);■ palliative systemic therapy for metastatic gastric cancer;■ optimum duration of preoperative radiation in rectal cancer-that is, short- compared with long-course radiation;■ management options for peritoneal carcinomatosis in crc;■ implications of tumour location for treatment and prognosis in crc; and■ new molecular markers in crc.

Eastern Canadian Colorectal Cancer Consensus Conference: standards of care for the treatment of patients with rectal, pancreatic, and gastrointestinal stromal tumours and pancreatic neuroendocrine tumours.

The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Halifax, Nova Scotia, October 20-22, 2011. Health care professionals involved in the care of patients with colorectal cancer participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management of rectal cancer, including pathology reporting, neoadjuvant systemic and radiation therapy, surgical techniques, and palliative care of rectal cancer patients. Other topics discussed include multidisciplinary cancer conferences, treatment of gastrointestinal stromal tumours and pancreatic neuroendocrine tumours, the use of folfirinox in pancreatic cancer, and treatment of stage ii colon cancer.

Eastern Canadian colorectal cancer consensus conference: application of new modalities of staging and treatment of gastrointestinal cancers.

The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Ottawa, Ontario, October 22-23, 2010. Health care professionals involved in the care of patients with colorectal cancer participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of colorectal cancer, such as the use of epidermal growth factor inhibitors in metastatic colon cancer, the benefit of calcium and magnesium with oxaliplatin chemotherapy, the role of microsatellites in treatment decisions for stage II colon cancer, the staging and treatment of rectal cancer, and the management of colorectal and metastatic pancreatic cancers.

Eastern Canadian Colorectal Cancer Consensus Conference: setting the limits of resectable disease.

The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Montreal, Quebec, October 22-24, 2009. Health care professionals involved in the care of patients with colorectal cancer participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management colorectal cancer, such as the management of hepatic and pulmonary metastases, the role of monoclonal antibodies to the epidermal growth factor receptor, and the benefits and safety of chemotherapy in elderly patients. The management of gastrointestinal neuroendocrine tumours and gastric cancer are also discussed.

Very preterm children show impairments across multiple neurodevelopmental domains by age 4 years.

OBJECTIVES: Neurodevelopmental outcomes associated with preterm birth are of major health and educational concern. This study examined the neuromotor, cognitive, language and emotional/behavioural outcomes of a regional cohort of 4-year-old children born extremely preterm (EPT: 23-27 weeks' gestation), very preterm (VPT: 28-33 weeks) and full term (FT: 38-41 weeks). Of particular interest were children's risks of impairment across multiple neurodevelopmental domains. METHODS: Data were gathered as part of a prospective longitudinal study of 105 very preterm (< or = 33 weeks gestation) and 107 FT children born during 1998-2000. At 4 years corrected age, children underwent a comprehensive multidisciplinary assessment that included a paediatric neurological examination, cognitive and language testing, and an assessment of child emotional and behavioural adjustment. RESULTS: At age 4 years, compared to FT children, EPT and VPT children had increased risks of cerebral palsy (EPT 18%, VPT 15%, FT 1%), cognitive delay (EPT 33%, VPT 36%, FT 13%), language delay (EPT 29%, VPT 29%, FT 10%) and emotional/behavioural adjustment problems (EPT 37%, VPT 13%, FT 11%). EPT and VPT children were three times more likely to have multiple domain impairments than FT children (EPT 30%, VPT 29%, FT 10%). CONCLUSIONS: A substantial proportion of preschool children born very preterm show clinically significant problems in at least one neurodevelopmental domain, with impairment in multiple domains being common. There is a need to monitor preschool development across a range of functional domains and to consider the likely cascading effects of multiple impairments on later development.

The utility of ambulatory pH monitoring in patients presenting with chronic cough and asthma.

OBJECTIVE: To evaluate the prevalence of gastroesophageal reflux disease (GERD) in patients presenting with asthma and chronic cough. PATIENTS AND METHODS: The charts of 358 consecutive patients who were referred for ambulatory gastroesophageal pH monitoring to the Lung Centre in Vancouver, British Columbia, were reviewed, and the data of 108 (30%) patients with asthma and 134 (37%) patients with chronic cough were analyzed. The maintenance treatment for GERD was discontinued before patients underwent the pH monitoring study. One hundred eighteen (33%) patients were excluded. RESULTS: Reflux episodes identified reflux events as the percentage of time where the pH was less than four. For asthma patients, 70 (64.8%) had distal total reflux, 50 (46.3%) had distal upright reflux, 41 (38.3%) had distal supine reflux and 73 (67.6%) had other distal refluxes. Proximal total reflux in asthmatic patients was present in 56 (52%), proximal upright reflux in 55 (51%) and proximal supine reflux in 56 (52%) patients. For chronic cough patients, 70 (52.6%) had distal total reflux, 59 (44.4%) had distal upright reflux, 45 (34.4%) had distal supine reflux and 75 (56%) patients had other distal refluxes. In chronic cough patients, proximal total reflux was present in 70 (52%), proximal upright reflux in 80 (60%) and proximal supine reflux in 59 (44%). Presenting respiratory and/or reflux symptoms were absent in approximately 25% of patients with asthma and reflux, and in approximately 50% of patients with chronic cough and reflux. During pH monitoring, symptoms did not differ significantly between those with and without distal reflux in both study groups, except for more significant heartburn in patients with chronic cough and reflux (RR 2.0). CONCLUSIONS: The data of the present study support the observation that there is a high prevalence of GERD in patients with asthma or chronic cough. The use of different pH parameters for detecting acid reflux during 24 h ambulatory pH monitoring, such as proximal esophageal acid measurement, should be considered as part of the routine interpretation of such testing. A low threshold for diagnosing GERD in patients with asthma or chronic cough is essential, because respiratory and/or reflux symptoms can be absent or atypical in some of these patients.

Diabetes care management participation in a primary care setting and subsequent hospitalization risk.

Scant evidence exists that examines the impact of participation in primary care diabetes management programs and their educational components on the risk of subsequent significant patient morbidity. This study examined the association between participation in a diabetes management program in a primary care setting and the risk of subsequent hospitalization. Ten thousand nine hundred eighty patients with diabetes mellitus receiving some type of treatment in a large primary care clinic network in Houston, TX were examined for incidence of hospitalization in the year 2002. Information from the year preceding the hospitalization was obtained on several demographic, clinical, and diabetes care management participation related variables. Multivariate logistic regressions were used to examine the relationship between primary care diabetes management participation as well as individual educational components and the likelihood of subsequent-year hospitalization. Patients participating in some type of primary care diabetes management were 16% less likely to have an incidence of hospitalization (p = 0.05). When individual educational components of the diabetes care management program were examined, diabetes education sessions were more beneficial than certified diabetes educator visits in reducing the incidence of hospitalization. Patients with controlled blood glucose levels and a diabetes education session seemed to have the most significant reduction in hospitalization risk (odds ratio [OR] = 0.62; 95% CI: 0.40, 0.95). There seem to be beneficial effects associated with participation in primary care diabetes management programs in terms of reduced hospitalization risk. Attendance at diabetes educational sessions in primary care settings coupled with maintenance of blood glucose control seem to be associated with greatest risk reduction.

Characterization of the oxygenated intermediate of the thermophilic cytochrome P450 CYP119.

Using UV-Vis, resonance Raman, and EPR spectroscopy we have studied the properties of the oxygenated ferrous cytochrome P450 from Sulfolobus solfataricus, (CYP119). The recently determined crystal structure of CYP119 is compared with other available structures of P450s, and detailed structural and spectroscopic analyses are reported. With several structural similarities to CYP102, such as in-plane iron position and a shorter iron-proximal ligand bond, CYP119 shows low-spin conformation preference in the ferric form and partially in the ferrous form at low temperatures. These structural features can explain the fast autoxidation of the oxyferrous complex of CYP119. Finally, we report the first UV-Vis and EPR spectra of the cryoradiolytically reduced oxygenated intermediate of CYP119. The primary reduced intermediate, a hydroperoxo-ferric complex of CYP119, undergoes a 'peroxide shunt' pathway during gradual annealing at 170-195 K and returns to the low-spin ferric form.

Long-range reactive dynamics in myoglobin.

We report the complete vibrational spectrum of the probe nucleus 57Fe at the oxygen-binding site of the protein myoglobin. The Fe-pyrrole nitrogen stretching modes of the heme group, identified here, probe asymmetric interactions with the protein environment. Collective oscillations of the polypeptide, rather than localized heme vibrations, dominate the low frequency region. We conclude that the heme "doming" mode is significantly delocalized, so that distant sites respond to oxygen binding on vibrational time scales. This has ramifications for understanding long-range interactions in biomolecules, such as those that mediate cooperativity in allosteric proteins.

Resonance Raman and EPR investigations of the D251N oxycytochrome P450cam/putidaredoxin complex.

We have performed resonance Raman and electron paramagnetic resonance (EPR) studies on the dioxygen bound state of the D251N mutant of cytochrome P450cam (oxy-P450cam) and its complex with reduced putidaredoxin (Pd). The D251N oxy-P450cam/Pd complex has a perturbed proton delivery mechanism and shows a significantly red-shifted UV-visible spectrum as observed in Benson et al. [Benson, D. E., Suslick, K. S., and Sligar, S. G. (1997) Biochemistry 36, 5104-5107]. The red shift has been interpreted to indicate a major perturbation of the electronic structure of the oxy-heme complex. However, we find no evidence that electron transfer has occurred from Pd to the heme active site of D251N oxy-P450cam. This suggests that both electron and proton transfer are perturbed by the D251N mutation and that these processes may be coupled. Three oxygen isotope sensitive Raman features are identified in the Pd complex, and occur at 1137, 536, and 399 cm(-1). These values are not significantly different from those for WT or D251N oxy-P450cam. However, a careful examination of the oxygen stretching feature near 1137 cm(-1) reveals the presence of three peaks at 1131, 1138, and 1146 cm(-1), which we attribute to the presence of conformational substates in oxy-P450cam. A significant change in the conformational substate population is observed for the D251N oxy-P450cam when the Pd complex is formed. We suggest that the conformational population redistribution of oxy-P450cam, along with the red-shifted electronic spectra, reflects a structural equilibrium of the oxy-heme that is perturbed upon Pd binding. We propose that this structural perturbation is connected to the effector function of Pd and may involve changes in the electron donation properties of the thiolate ligand.

Water penetration and binding to ferric myoglobin.

Flash photolysis investigations of horse heart metmyoglobin bound with NO (Mb(3+)NO) reveal the kinetics of water entry and binding to the heme iron. Photodissociation of NO leaves the sample in the dehydrated Mb(3+) (5-coordinate) state. After NO photolysis and escape, a water molecule enters the heme pocket and binds to the heme iron, forming the 6-coordinate aquometMb state (Mb(3+)H2O). At longer times, NO displaces the H2O ligand to reestablish equilibrium. At 293 K, we determine a value k(w) approximately 5.7 x 10(6) s(-1) for the rate of H2O binding and estimate the H2O dissociation constant as 60 mM. The Arrhenius barrier height H(w) = 42 +/- 3 kJ/mol determined for H2O binding is identical to the barrier for CO escape after photolysis of Mb(2+)CO, within experimental uncertainty, consistent with a common mechanism for entry and exit of small molecules from the heme pocket. We propose that both processes are gated by displacement of His-64 from the heme pocket. We also observe that the bimolecular NO rebinding rate is enhanced by 3 orders of magnitude both for the H64L mutant, which does not bind water, and for the H64G mutant, where the bound water is no longer stabilized by hydrogen bonding with His-64. These results emphasize the importance of the hydrogen bond in stabilizing H2O binding and thus preventing NO scavenging by ferric heme proteins at physiological NO concentrations.

Holmium: YAG lithotripsy: optimal power settings.

PURPOSE: We tested the hypothesis that holmium:YAG laser lithotripsy speed is best maximized by using low pulse energy at high pulse frequency. MATERIALS AND METHODS: To demonstrate that optical fiber damage increases with pulse energy and irradiation, the 365-microm optical fiber irradiated calcium hydrogen phosphate dihydrate (CHPD), calcium oxalate monohydrate (COM), cystine, magnesium ammonium phosphate hexahydrate (MAPH), and uric acid calculi at pulse energies of 0.5 to 2.0 J. Optical energy output was measured with an energy detector after 10 J to 200 J of total energy. To demonstrate that lithotripsy efficiency varies with power, fragmentation was measured at constant power settings at total energies of 200 J and 1 kJ with the 365-microm optical fiber. Fragmentation was measured for the 272-microm optical fiber at pulse energies of 0.5 J to 1.5 J at 10 Hz. To demonstrate that low pulse energy produces smaller fragments than high pulse energy, fragment size was characterized for COM and uric acid calculi after 0.25 kJ of irradiation using the 272-microm to 940-microm optical fibers at 0.5 J to 1.5 J. RESULTS: Damage to the 365-microm optical fiber was greatest for irradiation of CHPD, followed by MAPH, and COM (P<0.001). There was no significant optical fiber damage after cystine and uric acid lithotripsy. For the 365-microm optical fiber and CHPD, fragmentation after 200 J was greatest for pulse energies < or =1.0 J (P< 0.001). For other compositions, fragmentation was not statistically different among the power settings for constant irradiation. No significant difference was noted in fragmentation for any composition at different pulse energies (1.0 v. 2.0 J) for 1-kJ irradiation. However, for all compositions, the calculated lithotripsy speed was greatest at high power settings (P<0.001). For the 272-microm optical fiber, CHPD fragmentation was greatest for the 1.0-J pulse energy. The mean fragment size and relative quantity of fragments > or =2 mm both increased as pulse energy increased. CONCLUSIONS: Optical fiber degradation varies with stone composition, irradiation, and pulse energy. Holmium:YAG lithotripsy speed is maximized with higher power (either increased pulse energy or higher pulse frequency). Because low pulse energy may be safer and yields smaller fragments than high pulse energy, holmium:YAG lithotripsy speed is best increased by using pulse energies < or =1.0 J at a high repetition rate.

Post-surgical shunt hepatopulmonary syndrome in a case of non-cirrhotic portal hypertension: lack of efficacy of shunt reversal.

Hepatopulmonary syndrome, a consequence of significant liver disease and portal hypertension, is thought to be secondary to the effects of vasoactive substances, normally inactivated in the liver, on the pulmonary vasculature. We report a patient with preserved hepatic function who underwent a decompressive surgical porto-systemic shunt for non-cirrhotic portal hypertension. This patient developed hepatopulmonary syndrome with dyspnoea and oxygen desaturation 2 years post-surgical shunt. Over the next 7 years, the patient's respiratory function became increasingly impaired although hepatic function remained preserved. Because of the hypothesized role of porto-systemic shunting in the aetiology of this syndrome, the surgical shunt was successfully reversed angiographically. No improvement in dyspnoea or oxygen saturation occurred and liver transplantation was undertaken. Six months post-transplant, the patient has decreased his oxygen requirements and is free of dyspnoea. Our experience supports the causal role of porto-systemic shunting in the pathogenesis of hepatopulmonary syndrome but suggests that merely decreasing the extent of porto-systemic shunting is not beneficial. Liver transplantation remains the only reliable therapeutic modality available to these patients.

Holmium:YAG lithotripsy of uric acid calculi.

PURPOSE: Holmium:YAG lithotripsy of uric acid calculi produces cyanide. We review our experience with holmium:YAG lithotripsy of uric acid calculi to determine if there is any clinical evidence of cyanide toxicity. MATERIALS AND METHODS: A retrospective analysis of all of our cases of holmium:YAG lithotripsy of uric acid calculi was done. Anesthetic and postoperative data were reviewed. RESULTS: A total of 18 patients with uric acid calculi were treated with holmium:YAG lithotripsy by ureteroscopy (5), retrograde nephroscopy (2), percutaneous nephrolithotomy (5) or cystolithotripsy (6). No patient had increased end-tidal carbon dioxide, changes in electrocardiogram or significant decrease in postoperative serum bicarbonate. An 84-year-old woman had decreased diastolic pressure of 30 mm. Hg while under general anesthesia. No cyanide related neurological, cardiac or respiratory complications were noted. CONCLUSIONS: There were no obvious cyanide related complications from holmium:YAG lithotripsy of uric acid calculi. These data suggest no significant cyanide toxicity from holmium:YAG lithotripsy of uric acid calculi in typical clinical settings. Animal studies are warranted to characterize the risk.

A comparative study of the 1992 and 1997 recovery positions for use in the UK.

In April 1997 the ILCOR Basic Life Support advisory statements were announced in conjunction with changes to the recovery position for use in the UK. This study compared the new and old positions by using a questionnaire to assess how well each position satisfied the ILCOR statements. The study was carried out over six different hospital trusts by eight resuscitation training officers. Each tutor alternately taught the 1992 or 1997 recommended positions. After the practical session each student completed a questionnaire on ease of learning and use of the position, as well as other factors such as spinal stability. They were also asked to score the position when they were placed in recovery by other students. Their competency was assessed using the ALS criteria. Over the duration of the study 687 forms were suitable for analysis. For every question there was a significant trend in favour of the 92 position, with students finding the technique easier to learn and use, simpler for positioning for CPR and with less spinal movement during rolling. Possible sources of bias such as previous training, tutor or staff grade made no statistical difference to the results. When performed competently the 1997 position appears to cause less brachial compression, but other problems with learning or use of the 97 position outweigh this advantage. The 1992 position currently provides the best compromise between ease of use, spinal stability and other factors, and better satisfies the ILCOR advisory statements.

Spectroscopic effects of polarity and hydration in the distal heme pocket of deoxymyoglobin.

Distal pocket mutations at the E7 position (His64) of sperm whale deoxymyoglobin (deoxyMb) are used as a probe of distal pocket polarity and hydration. Changes of two key spectroscopic markers, the Fe-His(F8) stretch in the resonance Raman spectrum and the position of band III in the absorption spectrum, are monitored as the His64Tyr, His64Phe, His64Leu, and His64Gly mutations alter the distal heme pocket environment. The Fe-His vibration for the Phe, Leu, and Gly mutants is shifted to a lower frequency by 1-2 cm-1 relative to the Tyr mutant, wild type (WT), and native deoxyMb. Band III shifts to the red by approximately 4 nm ( approximately 70 cm-1) relative to WT and native deoxyMb for all the His64 mutants examined in this work. We correlate the small shift in the Fe-His frequency to the local electrostatic environment directly above the heme iron, affected by the presence of a localized water molecule in the heme pocket that is hydrogen-bonded to the E7 residue. The position of band III is roughly correlated to the displacement of the iron from the heme plane; however, the relatively large scatter in this correlation, as well as its dependence on distal pocket mutations, suggests that the heme pocket environment, particularly the E7 residue, also affects the energy of this transition.

Pulmonary nodules: differential diagnosis using 18F-fluorodeoxyglucose single-photon emission computed tomography.

OBJECTIVE: The objective of this study was to prospectively evaluate the feasibility and efficacy of single-photon emission computed tomography (SPECT) with 18F-fluorodeoxyglucose (FDG) for differentiating malignant from benign pulmonary nodules. SUBJECTS AND METHODS: Twenty-six patients with 28 radiologically indeterminate focal pulmonary lesions were examined. Fasting patients were injected with 5 MBq/kg of FDG (maximum dose, 370 MBq). Imaging was performed with dual-head SPECT cameras equipped with 511-keV collimators. RESULTS: Seventeen of 21 pathologically malignant nodules showed FDG uptake on SPECT imaging (sensitivity, 81%). None of the seven benign modules showed uptake (specificity, 100%). SPECT imaging with FDG was positive in all 16 malignant nodules that were larger than or equal to 2 cm in diameter. However, only one (20%) of five nodules smaller than 2 cm in diameter showed positive on SPECT imaging. CONCLUSION: Using current technology, we found FDG SPECT imaging useful for distinguishing benign from malignant pulmonary nodules that were larger than or equal to 2 cm in diameter. However, because of the relatively low sensitivity of SPECT, smaller malignant nodules were not adequately revealed.

Probing heme protein conformational equilibration rates with kinetic selection.

Double-pulse flash photolysis experiments on solutions of carbonmonoxymyoglobin (MbCO) are used to determine the time scale for protein conformational averaging. The interconversion times for transitions between the "open" and "closed" subpopulations of MbCO are found to be 10(-6)-10(-4)s, depending on solvent composition and temperature. In aqueous solution at 273 K, the interconversion rate is found to be 1.4 x 10(6)s. Since the interconversion rate is comparable to or slower than the geminate rebinding rate, we describe the geminate phase of the kinetics as a superposition of contributions from the open and closed states. Although geminate kinetics remain intrinsically nonexponential for both open and closed states near room temperature, we find that substates within these two subpopulations interconvert more rapidly than the geminate rebinding. These observations cannot be explained by a superposition of contributions from a quasicontinuous conformational distribution (Steinbach et al., 1991) and are probably due to the long-time tail of the relaxation of the protein (Tian et al., 1992). Bimolecular rebinding takes place at a statistically averaged rate, since the interconversion and relaxation rates are faster than the bimolecular kinetics. The geminate and bimolecular kinetics are analyzed quantitatively as a function of pH using this approach and the spectroscopically determined populations of the open and closed states. The analysis accounts for the observed kinetics and also successfully predicts the kinetic response observed in the double-pulse experiments. In aqueous solution at 273 K, the geminate amplitudes and rates are found to be I(0)g = 32% and k(0)g = 1.3 x 10(7)s(-1) for the open state and I(1)g = 9.3% and k(1)g = 1.4 x 10(6)s(-1) for the closed state. In 75% glycerol solution at 264 K, the dominant component of the geminate rebinding is characterized by I(0)g1 = 89% and k(0)g1 = 3.1 x 10(6)s(-1) for the open state and I(1)g1 = 26% and k(1)g1 = 3.1 x 10(6)s(-1) for the closed state. The fact that the interconversion rate is comparable to the geminate rate of the closed state in aqueous solution is consistent with the idea that the open state provides an important pathway for ligand escape from (or entry to) the heme pocket (Tian et al., 1993). The increased viscosity of 75% glycerol solution delays the closed--> open interconversion until the end of the geminate phase, which forces the ligand to find alternative pathways to the solution. This observation, in conjunction with the near equivalence of the geminate rates for the open and closed states in 75% glycerol solution, suggests that the solvent composition fundamentally alters the protein-ligand dynamics.

Cryptogenic organizing pneumonia. A report of 25 cases and a review of the literature.

Cryptogenic organizing pneumonia (COP), also known as bronchiolitis obliterans organizing pneumonia (BOOP), is an uncommon lung disease characterized by the presence of granulation tissue within the alveolar ducts and alveoli. Because of the limited published literature on this topic and limited information on outcome we reviewed our own experience over an 8-year period and also critically evaluated the literature. We reviewed all cases of COP diagnosed from 1985 through 1992 at Vancouver General Hospital: 25 patients (14 male, 11 female) aged 20-77 years (mean, 49 yr, SD +/- 17 yr). Nine patients had myeloproliferative disorder, including 6 who had allogenic bone marrow transplants; 2 patients had connective tissue disease; and 14 patients had no underlying disease (idiopathic). Data retrieved retrospectively from clinical records included demographics, risk factors, symptoms, chest radiographs, computerized tomograms, lung function tests, therapy prescribed, and response to therapy. Symptoms included dyspnea and cough (n = 15) (60%), cough only (n = 10) (40%), and fever (n = 15) (60%). Twenty-two patients were diagnosed by open lung biopsy and 3 by transbronchial biopsy. Lung imaging showed bilateral patchy airspace consolidation or nodular opacities as the main finding in 22 patients. Pulmonary function tests showed a combined restrictive and obstructive pattern. All patients received prednisone therapy except 1 patient whose idiopathic findings resolved completely with minimal treatment. Eight patients died, including 4 of the 9 patients with myeloproliferative disorder--2 from a combination of respiratory failure due to COP and graft-versus-host disease. One of 2 patients with connective tissue disease died, and 3 of 14 patients with idiopathic COP died. COP is an uncommon condition but should be considered in patients with bilateral airspace disease, especially those who fail to respond to antibiotics for presumed pneumonia. Although pulmonary function tests and CT scan findings in conjunction with the clinical features usually suggest the diagnosis, definite confirmation usually requires either open lung biopsy or transbronchial biopsy. Histologic confirmation of the diagnosis is particularly warranted as therapy with corticosteroids is usually needed for a number of months. The prognosis is excellent with idiopathic cases but more guarded especially when COP is associated with lymphoproliferative or connective tissue disease.