Hyperostosis may affect prognosis after primary endoscopic sinus surgery for chronic rhinosinusitis.

OBJECTIVE: To investigate the independent effect of hyperostosis on outcome after endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS). STUDY DESIGN AND SETTING: The medical records of 81 consecutive patients who had undergone primary ESS for CRS were reviewed retrospectively. Sinus CT scans were evaluated for the presence of hyperostosis to investigate the association with postoperative outcomes. The independent effect of hyperostosis on surgical outcome was analyzed, controlling for possible confounding factors with a multiple logistic regression model. RESULTS: Sixty percent of the patients showed hyperostosis, and there was a statistically significant association between the hyperostosis and postoperative outcome (P = 0.035, chi(2) test), which was confirmed after adjustment for the possible confounding factors (P = 0.048, odds ratio [OR] = 3.19, logistic regression analysis). CONCLUSIONS: Our study suggests that patients with CRS who have hyperostosis may have a poorer surgical outcome than those without hyperostosis. EBM rating: B-2b.     

Biofilm formation by Staphylococcus aureus and Pseudomonas aeruginosa is associated with an unfavorable evolution after surgery for chronic sinusitis and nasal polyposis

OBJECTIVES: To determine whether biofilm-forming capacity of bacteria demonstrated in chronic rhinosinusitis (CRS) has an impact on persistence of the disease following endoscopic sinus surgery (ESS). METHOD: Thirty-one bacterial strains recovered from 19 patients with CRS at least 1 year post-ESS. Evolution of disease was assessed by questionnaire and endoscopy as favorable or unfavorable. The bacteria were cultured on a 96-well culture plaque and a semi-quantitative method using crystal violet to quantify biofilm production was used. RESULTS: Twenty-two of 31 samples produced a biofilm thicker or equal to the positive control. Biofilm production was noted in 6/10 Pseudomonas aeruginosa isolates, 8/10 Staphylococcus aureus, and 8/11 coagulase-negative staphylococci. Biofilm formation was associated with a poor evolution for Pseudomonas aeruginosa and Staphylococcus aureus, but not coagulase-negative staphylococcus. CONCLUSION: There is a correlation between in vitro biofilm-producing capacity by Pseudomonas aeruginosa and Staphylococcus aureus and unfavorable evolution after ESS, suggesting a role for biofilm production in chronic sinusitis. EBM RATING: B-2b.     

Neoadjuvant radiochemotherapy of oral cavity and oropharyngeal cancer: evaluation of tumor response by CT differs from histopathologic response assessment in a significant fraction of patients

BACKGROUND: Our aim was to compare and assess the predictive value of CT and histopathologic grading of tumor regression at primary tumor sites in patients with squamous cell carcinoma of the oral cavity and oropharynx after neoadjuvant (preoperative) radiochemotherapy (RCT). METHODS: We investigated 55 patients with carcinomas of the oral cavity and oropharynx who underwent RCT before curative surgery. Two blinded observers measured RCT-induced reduction of tumor volume in pretherapeutic and posttherapeutic CT scans. Volume changes were compared with histopathologic findings obtained at surgery. RESULTS: Histopathologic response evaluation revealed 31 complete remissions, 12 cases of partial response, and 12 nonresponders. We performed a logistic regression analysis to evaluate whether measured volume reduction could predict the likelihood of belonging to a certain response group. Taken together, we found 35 correct, 12 false-negative, and seven false-positive predictions. CONCLUSIONS: The extent of remission as assessed by CT scans 4 to 5 weeks after completion of neoadjuvant RCT leads to false predictions in a significant percentage of patients.     

Effect of endoscopic sinus surgery on asthmatic patients with chronic rhinosinusitis.

There have been several reports on the effectiveness of endoscopic sinus surgery (ESS) in asthmatic patients with chronic rhinosinusitis. Whether ESS has a positive effect on the clinical course of asthma still remains controversial. There have been several subjective evaluations but few objective results. We performed a study to evaluate the effectiveness of ESS in 19 patients with asthma who underwent ESS for rhinosinusitis. The use of antiasthma medication and postoperative asthma symptoms was analyzed. Objective changes of pulmonary function tests were evaluated. There was a significant improvement in diurnal and nocturnal asthma symptoms. Improvements in asthma medication scores were also confirmed, and individual asthma symptoms (dyspnea, cough, wheezing, and sputum production) improved significantly. Despite a reduction in use of antiasthma medication after ESS, the parameters of the pulmonary function tests did not change. Both subjectively and objectively, it seems that ESS, when used to treat asthmatic patients with chronic rhinosinusitis, can play a significant role in the clinical improvement of asthma.     

Prognostic Value of Circulating Tumor Markers in Patients with Pseudomyxoma Peritonei Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Background Encouraging results have been recently reported in selected patients affected by pseudomyxoma peritonei (PMP) treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The selection factors predicting clinical outcome are still a matter of clinical investigation. We assessed the prognostic reliability of serum tumor markers in a large series of patients with PMP undergoing CRS and HIPEC. Methods Sixty-two patients with PMP were operated on at a single institution with the intent of performing adequate CRS (residual tumor nodules ≤2.5mm) and HIPEC. Baseline and serial marker measurements were prospectively collected and tested by multivariate analysis with respect to adequate cytoreduction, overall (OS) and progression-free (PFS) survival, along with the following variables: age, sex, performance status, prior surgical score, histological subtype, prior systemic chemotherapy, disease extent, completeness of cytoreduction. Results Baseline diagnostic sensitivity was 72.6% for CEA, 58.1% for CA19.9, 58.7% for CA125, 36.1% for CA15.3. Fifty-three patients underwent adequate CRS and HIPEC; gross residual tumor was left after surgery in nine. Adequate CRS was performed in 19/27 patients with elevated and in 19/19 with normal baseline CA125 (P = .0140). The other markers were unable to predict the completeness of CRS by univariate analysis. Baseline elevated CA19.9 was an independent predictor of reduced PFS; inadequate CRS and aggressive histology were independent prognostic factors for both reduced OS and PFS. Conclusion Normal CA125 correlated to the likelihood to achieve adequate CRS, which is a significant prognostic factor for PMP. Increased baseline CA19.9 was an independent predictor of worse PFS after CRS and HIPEC.     

Preoperative treatment with topical corticoids and bleeding during primary endoscopic sinus surgery

Objective

To find out whether the constant preoperative use of a topical corticoid (mometasone furoate [MF]) could really improve the operative field quality and decrease bleeding during endoscopic sinus surgery (ESS).

Study Design

Double-blind, randomized controlled trial.

Setting

Tertiary referral center.

Subjects and Methods

Seventy patients with chronic rhinosinusitis (CRS) with and without polyps underwent ESS under standardized general anesthesia with equal randomization into two groups. During four weeks within the preoperative period, 35 cases were treated with MF, while the other half received placebo matching sprays. Total blood loss, operation time, and surgical field quality were recorded.

Results

Intraoperative blood loss in the MF-treated group was 142.8 mL, less than in the control group (170.6 mL). The difference between the groups is 27.7 mL (95% confidence interval [CI] 3.5-51.92), statistically significant: P = 0.025. Time of surgery was 59 minutes in the MF group and 70 minutes in the control group. The difference was 11.2 minutes (95% CI 2.82-19.51), which is statistically significant: P = 0.009. The quality of the endoscopic surgical field was significantly better for patients treated with MF. Treatment with topical corticoid enables significantly reduced bleeding, decreased operation time, and improved endoscopic vision during ESS for CRS.

Conclusion

The use of topical corticoid (MF) in the preoperative period can improve endoscopic vision, reduce bleeding, and decrease operation time in CRS patients with and without polyps undergoing ESS, but our sample size cannot exclude small, and possibly trivial, group differences.     

Neoadjuvant therapy of esophageal squamous cell carcinoma: response evaluation by positron emission tomography

OBJECTIVE: To evaluate the use of positron emission tomography using [(18)F]-fluorodeoxyglucose (FDG-PET) to assess the response to neoadjuvant radiotherapy and chemotherapy in patients with locally advanced esophageal cancer. SUMMARY BACKGROUND DATA: Imaging modalities, including endoscopy, endoscopic ultrasound, computed tomography, and magnetic resonance imaging, currently used to evaluate response to neoadjuvant treatment in esophageal cancer do not reliably differentiate between responders and nonresponders. METHODS: Twenty-seven patients with histopathologically proven squamous cell carcinoma of the esophagus, located at or above the tracheal bifurcation, underwent neoadjuvant therapy consisting of external-beam radiotherapy and 5-fluorouracil as a continuous infusion. FDG-PET was performed before and 3 weeks after the end of radiotherapy and chemotherapy (before surgery). Quantitative measurements of tumor FDG uptake were correlated with histopathologic response and patient survival. RESULTS: After neoadjuvant therapy, 24 patients underwent surgery. Histopathologic evaluation revealed less than 10% viable tumor cells in 13 patients (responders) and more than 10% viable tumor cells in 11 patients (nonresponders). In responders, FDG uptake decreased by 72% +/- 11%; in nonresponders, it decreased by only 42% +/- 22%. At a threshold of 52% decrease of FDG uptake compared with baseline, sensitivity to detect response was 100%, with a corresponding specificity of 55%. The positive and negative predictive values were 72% and 100%. Nonresponders to PET scanning had a significantly worse survival after resection than responders. CONCLUSION: FDG-PET is a valuable tool for the noninvasive assessment of histopathologic tumor response after neoadjuvant radiotherapy and chemotherapy.     

Effect of tumor-infiltrating lymphocyte subsets on prognosis and susceptibility to interferon therapy in patients with renal cell carcinoma

INTRODUCTION: Immunotherapy effectively treats advanced renal cell carcinoma in only a limited number of patients. However, the predicted prognosis for each patient in relation to immune status and response to immunotherapy remains problematic. We analyzed tumor-infiltrating lymphocyte (TIL) subsets to determine whether these correlated with the prognoses for the patients and the response to alpha-interferon therapy. MATERIALS AND METHODS: TIL subsets from resected specimens of 79 patients were analyzed by two-color flow cytometry and then compared with the patients' long-term clinical courses and responses to interferon therapy. RESULTS: In patients with stages III and IV, an increased infiltration of CD4+ cells and decreased CD8+ cells constituted a fair prognostic factor. In 17 patients with metastatic lesions, 8 of 10 patients who had disease progression after interferon therapy showed an increase in CD8+ cells above 25%, whereas 2 responders and 5 patients who had stable disease showed infiltration of CD8+ cells below 25%. CONCLUSIONS: The TIL subset is a prognostic factor for advanced renal cell carcinoma, and its analysis provides a method to predict the susceptibility to interferon therapy.     

Patient expectations and recovery following endoscopic sinus surgery.

OBJECTIVES: Studies examining the early postoperative period after endoscopic sinus surgery (ESS) are lacking. The objectives were to determine patient expectations of recovery following ESS and compare these expectations to actual outcomes. STUDY DESIGN: A prospective study. An 11-item survey regarding recovery from anesthesia and sinonasal outcomes was administered after ESS over postoperative days (POD) #1, #7, and #14. Preoperative surveys established baseline levels and explored patient expectations of POD #1 outcomes. RESULTS: Forty-six patients participated. Individual expectations generally did not correlate with POD #1 outcomes. Sinonasal symptoms, narcotic usage, and activity level (P < 0.05) demonstrated significant improvement over the postoperative period. Within one week, 75% of patients returned to work. By POD #14, nasal obstruction, discharge, fatigue, and overall health (P < 0.05) had improved over preoperative levels. Patients undergoing concomitant septoplasty had a more difficult postoperative course. CONCLUSION: Patient expectations of ESS vary widely, although this surgery is generally well tolerated with a brief recovery period. EBM rating: C-4.     

The relationship between tumor thickness and clinical and histopathologic parameters in cancer of the larynx.

OBJECTIVES: We sought to determine the relationship of tumor thickness to clinical and histopathologic parameters in laryngeal cancer.Study design and setting We conducted a retrospective review of laryngectomy specimens of 111 surgically treated T1-3 laryngeal cancer patients for tumor thickness and various histopathologic parameters. RESULTS: Tumor thickness was significantly related to T, N, and clinical stage; pathologic cervical lymph node metastasis; cartilage invasion; microscopic appearance; mode of invasion to surrounding tissues; perineural invasion; and lymphocytic infiltration (P < 0.05). Tumor thickness had significant correlation with T, N, and clinical stage; cervical lymph node metastasis; cartilage invasion; mode of invasion to surrounding tissues; perineural invasion; and lymphocytic infiltration (P < 0.05). Multifactorial statistical analysis showed that cartilage invasion and lymphocytic infiltration significantly determined tumor thickness independently (P < 0.05). CONCLUSION: Tumor thickness is well correlated to most of the reliable clinical and histopathologic parameters, and it is an objective and easy-to-obtain measure. SIGNIFICANCE: Tumor thickness can be used as a reliable histopathological factor and should be measured in every laryngectomy specimen.     

鼻内镜手术治疗少年患者的鼻腔结构异常

目的探讨药物治疗无效的少年慢性鼻-鼻窦炎患者的内镜治疗方式与效果。方法因鼻腔结构异常伴发慢性鼻-鼻窦炎行鼻内镜手术治疗的少年患者112例,年龄12~17岁。在鼻内镜下行鼻中隔成形术,酌情行中鼻甲、下鼻甲成形术,合并腺样体肥大及鼻息肉者同期处理。结果随访6~23个月,平均13个月,术后症状消失110例(98.2%),无明显改善2例(1.8%)。结论鼻内镜下鼻中隔成形术,结合中鼻甲或下鼻甲成形,手术细致、微创,可以有效纠正少年患者鼻腔结构异常,解决药物不能解决的解剖问题,为鼻腔生理功能的恢复创造条件。     

Outcome predictors for endoscopic sinus surgery.

OBJECTIVE: The outcomes management of endoscopic sinus surgery (ESS) is a major effort to improve the quality of chronic sinusitis treatment. The objective of this study was to investigate the factors that may predict a variety of outcomes of ESS. STUDY DESIGN AND SETTING: Two hundred and thirty consecutive patients who underwent ESS were prospectively evaluated by computerized axial tomography scan of the sinus and a validated chronic sinusitis survey (CSS) before surgery. The effects of prognostic factors were then investigated. RESULTS: Extent of disease was a consistent predictor (P < 0.05) for bleeding, complication occurrence, medical resource utilization, subjective sinus-specific health status, and physicians' objective evaluation of surgical outcomes. The preoperative CSS total score and extent of disease significantly (P < 0.05) predicted the postoperative CSS total score. Subjective and objective outcomes were significantly correlated (r = 0.58, P = 0.0001). These findings suggested the necessity of disease severity stratification when reporting ESS outcomes. CONCLUSION: Operation-related events, medical resource utilization, physician evaluation, and sinus-specific health status of patients are all integral parts of reporting outcomes of ESS. We have concluded that computerized axial tomography scan of the sinuses and CSS are efficient ways of providing reliable baseline information before ESS.     

Symptom and disease severity differences between nasal septal deviation and chronic rhinosinusitis.

OBJECTIVE: To determine whether patients with chronic rhinosinusitis (CRS) exhibit more severe sinonasal symptom scores as compared with patients with nasal septal deviation (NSD) alone. METHODS: Two patient cohorts were prospectively identified: patients undergoing surgery for NSD alone and those undergoing endoscopic sinus surgery for CRS without NSD. Patients in the NSD group were required to have normal paranasal sinus CT scans, whereas patients in the CRS group were required to have radiographic evidence of CRS. All patients completed the Rhinosinusitis Symptom Inventory (RSI). Statistical comparisons were conducted between cohorts with respect to RSI symptom domains and medical resource utilization. RESULTS: A total of 42 patients were identified in the NSD group (mean age, 40.8 years) and 155 patients were identified in the CRS group (mean age, 44.9). Patients with CRS demonstrated higher severity scores for the nasal symptom domains (60.3 [CRS] versus 53.9 [NSD], P = 0.037). Oropharyngeal symptoms and total symptoms were also worse for the CRS group versus the NSD group (29.8 versus 23.1, P = 0.014 and 43.0 versus 37.0, P = 0.030). Facial and systemic symptom scores did not differ between groups. Patients with CRS demonstrated significantly higher utilization rates for topical nasal steroids (21.2 versus 12.2 weeks, P = 0.006) and oral antibiotics (7.9 weeks versus 2.1 weeks, P < 0.001), but not for oral antihistamines (P = 0.420). CONCLUSIONS: Although patients with CRS manifest higher sinonasal symptom scores than patients with NSD alone, differentiating these 2 diagnoses on the basis of symptoms alone is difficult. These data suggest that as a disease process, CRS confers a significant disease burden with more significant negative symptom impact.     

Clinical predictors of long-term success after endoscopic sinus surgery.

OBJECTIVE: Determining the clinical predictors of long-term success after endoscopic sinus surgery (ESS) would better guide the management of patients. METHODS: One hundred-thirty chronic rhinosinusitis (CRS) patients were evaluated retrospectively. Overall subjective improvement was 83% with a mean follow-up of 60 months. Eighty percent had anatomic variations; 36.2%, allergy; 55.4%, nasal polyps; and 26.9%, history of previous operation. The improvement was 100%, 94%, 79.5%, and 69.7% in stages 0, I, II, and III, respectively. With other parameters, the success rates were 68.1% and 91.6% with and without allergy, 73.6% and 94.8% with and without polyps, 54.3% and 93.7% with and without previous history of surgery, 84.4% and 82.7% with and without anatomic variations, and 23.8% and 94.4% with and without recurrent polyps. CONCLUSION: In multivariate Cox regression analysis, allergy (P < 0.05; relative risk, 4.6) and previous polypectomy (P < 0.05; relative risk, 9.9) were found to be predictors of poor prognosis in the long-term follow-up.     

Clinical Predictors of Sleep Apnea in Patients Undergoing Bariatric Surgery

Background: Sleep apnea is a frequent and unappreciated condition of morbidly obese patients. If unrecognized it could lead to significant postoperative complications. A clinical tool to assess the severity of sleep apnea is not available.We prospectively determined whether the Epworth Sleepiness Scale (ESS) or body mass index (BMI) predict the severity of sleep apnea in morbidly obese patients. Methods: 66 consecutive patients evaluated for bariatric surgery from June to November 1999 were examined and prospectively administered a health questionnaire including the ESS. Patients with an ESS ≥ 6 were referred for polysomnography with calculation of Respiratory Disturbance Index (RDI). Sleep apnea was graded as mild (RDI 6-20), moderate (RDI 21-40) and severe (RDI>40). Clinical variables such as BMI and ESS score were compared using regression analysis. Data are mean ± SEM. Results: 4 men and 23 women (27/66) who scored >6 on the ESS completed a sleep study. Mean ESS was 13 ± 4.5. Sleep apnea was mild in 13 patients, moderate in 7, severe in 6, and absent in 1. Mean age was 43 ± 9.5 years. BMI was 52 ± 10 kg/m². Linear regression analysis did not demonstrate correlation between ESS score and severity of sleep apnea (r²=0.03, p>0.05). Multiple regression analysis demonstrated no correlation between BMI, patient snoring, and RDI score. Conclusions: Sleep apnea is frequent in candidates screened for bariatric surgery. ESS is a useful tool to investigate daytime sleepiness and other manifestations of sleep apnea. However, the ESS does not predict the severity of sleep apnea. Clinical suspicion of sleep apnea should prompt polysomnography.     

CT analysis and histopathology of bone remodeling in patients with chronic rhinosinusitis.

OBJECTIVE: To evaluate the findings of computed tomography (CT) and histopathology of the bulla ethmoidalis as objective markers of bone remodeling in chronic rhinosinusitis (CRS). METHODS: Preoperative ostiomeatal unit (OMU) scans and histopathologic findings of the bulla ethmoidalis were performed on 23 patients (39 sides) undergoing endoscopic sinus surgery for CRS. Lund-Mackay scores and Hounsfield units (HU) of the bulla were checked in coronal CT scans. The pathologist graded the severities of the mucosal and bony changes in histopathology. Statistical analysis was performed using Mann-Whitney U test and Spearman correlation coefficient (r). RESULTS: The HU values of the bulla were significantly increased with higher Lund-Mackay scores in OMU CT (r = 0.405, P = 0.01). The bony grades in histopathology were significantly increased with higher mucosal grades (r = 0.821, P = 0.0001). These findings in CT scans and histopathology were well correlated with each other (r > 0.3, P < 0.05). CONCLUSION: HU may be a useful objective marker of bone remodeling in chronic rhinosinusitis.     

Psychiatric distress amplifies symptoms after surgery for chronic rhinosinusitis.

BACKGROUND: Psychiatric disorders are associated with increased symptom burden when combined with chronic medical conditions. However, there are no reports of how psychiatric distress influences outcomes with surgical treatment for chronic rhinosinusitis (CRS). We hypothesized that subjects with psychiatric distress (somatization, anxiety, and depression) would report more severe long-term sinus symptoms and worse quality of life (QOL) than subjects without psychiatric distress. METHODS: This is a community-based, prospective, observational cohort study of patients diagnosed with CRS presenting for surgery. Patients were interviewed before surgery; CT scans were reviewed, and questionnaires were completed about sinusitis-related symptoms (SNOT-16), general health status and QOL (SF-36), and psychiatric distress (BSI and PHQ). Outcomes were also assessed 1, 3, 6, and 12 months postoperatively. RESULTS: Ninety-five patients had complete records for analysis. Psychiatric distress was prevalent, with 31% screening positive for somatization, 17% positive for anxiety, and 25% positive for depressive disorders. Subjects with somatization had significantly worse SNOT-16 scores at each time point compared with those without somatization ( P < 0.05). Subjects with depression reported more severe symptoms at 6 and 12 months after surgery than those without depression ( P < 0.05). The presence of somatization preoperatively was also independently associated with worse symptom severity 12-months after surgery, even after adjusting for prior sinus surgery, CT stage, Charlson Index, and deviated septum. In addition, subjects with psychiatric distress reported significantly worse SF-36 physical and mental component summary scores 12-months after surgery than subjects without psychiatric distress. CONCLUSIONS: Psychiatric distress is associated with worse reported sinus symptoms and lower QOL throughout surgical management of chronic rhinosinusitis. Despite this, subjects with psychiatric distress report a similar degree of improvement in sinus symptoms after surgery compared with those without distress. CLINICAL SIGNIFICANCE: Psychiatric distress should be considered in patients with persistent symptoms after surgery. Psychiatric distress should also be considered in efforts to design a chronic sinusitis staging system.     

Long-term clinical and pathologic response of Barrett's esophagus after antireflux surgery

BACKGROUND: The impact of antireflux surgery on outcome in Barrett's esophagus, in particular its effect on both the regression of metaplasia and the progression of metaplasia through dysplasia to adenocarcinoma, remains unclear. This long-term follow-up study evaluated clinical, endoscopic, histopathologic, and physiologic parameters in patients with Barrett's esophagus who underwent antireflux surgery in a specialist unit. METHODS: Between 1985 and 2001, 58 patients with Barrett's esophagus (49 long-segment and 9 short-segment) underwent a Rossetti-Nissen fundoplication, 32 via open procedure and 26 laparoscopically. Symptomatic follow-up with a detailed questionnaire was available in 58 (100%) and follow-up endoscopy and histology in 57 (98%) patients, and 41 patients (71%) underwent preoperative and postoperative 24-hour pH monitoring. RESULTS: At a median follow-up of 59 months, 52 patients (90%) had excellent symptom control, whereas 6 patients (10%) had significant recurrent symptoms and were on regular proton pump inhibitor medication. Seventeen of 41 patients having preoperative and postoperative pH monitoring (41%) had a persistent increase of acid reflux above normal. Thirty-five percent (20 of 57) of patients showed either partial or complete regression of Barrett's epithelium. Six of 8 patients with preoperative low-grade dysplasia showed evidence of regression. Dysplasia developed after surgery in 2 patients, and 2 patients developed adenocarcinoma at 4 and 7 years after surgery. All 4 of these patients had abnormal postoperative acid scores. CONCLUSIONS: Nissen fundoplication provides excellent long-lasting relief of symptoms in patients with Barrett's esophagus and may promote regression of metaplasia and dysplasia. Control of symptoms does not concord fully with abolition of acid reflux. Progression of Barrett's to dysplasia and tumor was only evident in patients with abnormal postoperative acid scores, suggesting that pH monitoring has an important role in the follow-up of surgically treated patients.     

Early and late chemokine production correlates with cellular recruitment in cardiac allograft vasculopathy

BACKGROUND: Cardiac allograft vasculopathy (CAV) remains the leading cause of late mortality in heart transplant recipients. Activated T lymphocytes and macrophages infiltrate the donor heart before vascular intimal thickening develops, but the specific mediators of mononuclear cell recruitment leading to CAV are unknown. Therefore, we sought to define the relationship between chemokine gene expression and production, T lymphocyte and macrophage recruitment, and intimal thickening in a murine model of CAV. METHODS: B10.A or B10.BR strain hearts were transplanted heterotopically into B10.BR mice. Recipients were killed at 1, 4, 7, 14, and 30 days. Donor hearts were assayed for chemokine gene expression with ribonuclease protection and for protein with ELISA. Intragraft cellular infiltration was defined immunohistochemically. Intimal thickening was quantitated morphometrically. RESULTS: Early and late patterns of intragraft chemokine expression associated with distinct cellular infiltration were identified. First, transient MIP-2 and MCP-1/JE production in isografts and allografts correlated with neutrophil and macrophage infiltration. MCP-1/JE production and macrophage infiltration was greater in allografts than isografts. Second, allografts demonstrated sustained lymphotactin, RANTES, and IP-10 expression, beginning at day 4, correlating with persistent macrophage and T lymphocyte infiltration. Intimal thickening became evident at 14 days. Isografts did not display the late pattern of sustained chemokine gene expression, cellular infiltration, or intimal thickening. CONCLUSIONS: Transient, early MIP-2, and MCP-1/JE production in isografts and allografts correlated with neutrophil and macrophage recruitment, and is likely related to ischemia-reperfusion. In allografts, the delayed induction of chemokines specific for macrophages and T lymphocytes correlated with mononuclear cell infiltration and preceded intimal thickening. This study thus demonstrates a dual pattern of chemokine induction correlating with intragraft mononuclear cell recruitment, associated with ischemia-reperfusion and CAV development. Chemokine-directed interventions may interfere with leukocyte trafficking and inhibit CAV development.     

Gastric Bypass is an Effective Treatment for Obstructive Sleep Apnea in Patients with Clinically Significant Obesity

Background: We have demonstrated that obstructive sleep apnea (OSA) is prevalent in 60% of patients undergoing bariatric surgery. A study was conducted to determine whether weight loss following bariatric surgery ameliorates OSA. Methods: All 100 consecutive patients with symptoms of OSA were prospectively evaluated by polysomnography before gastric bypass. Preoperative and postoperative scores of Epworth Sleepiness Scale (ESS), Respiratory Disturbance Index (RDI), and other parameters of sleep quality were compared using t-test. Results: Preoperative RDI was 40±4 (normal 5 events/hour, n=100). 13 patients had no OSA, 29 had mild OSA, while the remaining 58 patients were treated preoperatively for moderate-severe OSA. At a median of 6 months follow-up, BMI and ESS scores improved (38±1 vs 54±1 kg/m², 6±1 vs 12±0.1, P<0.001, postoperatively vs preoperatively). To date, 11 patients have completed postoperative polysomnography (3-21 months) after losing weight (BMI 40±2 vs 62±3 kg/m², P<0.001).There was significant improvement in ESS (3±1 vs 14±2), minimum O₂ saturation (SpO₂ 86±2 vs 77±5), sleep efficiency (85±2% vs 65±5%), all P<0.001, postop vs preop; and RDI (56±13 vs 23±7, P=0.041). Regression analysis demonstrated no correlation between preoperative BMI, ESS score and the severity of OSA; and no correlation between % excess body weight loss and postoperative RDI. Conclusion: Weight loss following gastric bypass results in profound improvement in OSA. The severity of apnea cannot be reliably predicted by preoperative BMI and ESS; therefore, patients with symptoms of OSA should undergo polysomnography.