Phase II study of neoadjuvant therapy with docetaxel, cisplatin, panitumumab, and radiation therapy followed by surgery in patients with locally advanced adenocarcinoma of the distal esophagus (ACOSOG Z4051).

BACKGROUND: Preoperative chemoradiotherapy (CRT) improves outcomes in patients with locally advanced but resectable adenocarcinoma of the esophagus. ACOSOG Z4051 evaluated CRT with docetaxel, cisplatin, and panitumumab (DCP) in this patient group with a primary end point of a pathologic complete response (pCR) ≥35%. PATIENTS AND METHODS: From 15 January 2009 to 22 July 2011, 70 patients with locally advanced but resectable distal esophageal adenocarcinoma were enrolled. Patients received docetaxel (40 mg/m(2)), cisplatin (40 mg/m(2)), and panitumumab (6 mg/kg) on weeks 1, 3, 5, 7, and 9 with RT (5040 cGy, 180 cGy/day × 28 days) beginning week 5. Resection was planned after completing CRT. PCR was defined as no viable residual tumor cells. Secondary objectives included near-pCR (≤10% viable cancer cells), toxicity, and overall and disease-free survival. Adverse events were graded using the CTCAE Version 3.0. RESULTS: Five of 70 patients were ineligible. Of 65 eligible patients (59 M; median age 61), 11 did not undergo surgery, leaving 54 assessable. PCR rate was 33.3% and near-pCR was 20.4%. Secenty-three percent of patients completed DCP (n = 70) and 92% completed RT. 48.5% had toxicity ≥grade 4. Lymphopenia (43%) was most common. Operative mortality was 3.7%. Adult respiratory distress syndrome was encountered in two patients (3.7%). At median follow-up of 26.3 months, median overall survival was 19.4 months and 3-year overall survival was 38.6% (95% confidence interval 24.5% to 60.8%). CONCLUSIONS: Neoadjuvant CRT with DCP is active (pCR + near-pCR = 53.7%) but toxicity is significant. Further evaluation of this regimen in an unselected population is not recommended. CLINICALTRIALSGOV IDENTIFIER: NCT00757172.

Surveillance for highly pathogenic avian influenza in migratory shorebirds at the terminus of the East Asian-Australasian Flyway.

AIM: To determine if migratory birds arriving in New Zealand in the Southern Hemisphere spring of 2004 were infected with the highly pathogenic avian influenza (AI) virus, H5N1. METHODS: Cloacal and faecal samples were collected from migratory red knots following their arrival in New Zealand in October 2004. Two species of resident sympatric birds, wrybill and mallard duck, were sampled prior to, and following, the arrival of migratory birds. RESULTS: No AI viruses were isolated from migratory or resident shorebirds. Non-pathogenic AI viruses were isolated from six resident mallard ducks, comprising the endemic subtypes H4 (n=2), H7 (non-pathogenic), H10, and H11 (n=2). CONCLUSIONS: Highly pathogenic AI H5N1 virus was not detected in migratory shorebirds or sympatric water birds in the Firth of Thames, New Zealand, in 2004-2005, despite the possible proximity of migratory birds to outbreaks of the disease in East Asia in 2004.

Worldwide esophageal cancer collaboration.

The aim of this study is to report assemblage of a large multi-institutional international database of esophageal cancer patients, patient and tumor characteristics, and survival of patients undergoing esophagectomy alone and its correlates. Forty-eight institutions were approached and agreed to participate in a worldwide esophageal cancer collaboration (WECC), and 13 (Asia, 2; Europe, 2; North America, 9) submitted data as of July 1, 2007. These were used to construct a de-identified database of 7884 esophageal cancer patients who underwent esophagectomy. Four thousand six hundred and twenty-seven esophagectomy patients had no induction or adjuvant therapy. Mean age was 62 +/- 11 years, 77% were men, and 33% were Asian. Mean tumor length was 3.3 +/- 2.5 cm, and esophageal location was upper in 4.1%, middle in 27%, and lower in 69%. Histopathologic cell type was adenocarcinoma in 60% and squamous cell in 40%. Histologic grade was G1 in 32%, G2 in 33%, G3 in 35%, and G4 in 0.18%. pT classification was pTis in 7.3%, pT1 in 23%, pT2 in 16%, pT3 in 51%, and pT4 in 3.3%. pN classification was pN0 in 56% and pN1 in 44%. The number of lymph nodes positive for cancer was 1 in 12%, 2 in 8%, 3 in 5%, and >3 in 18%. Resection was R0 in 87%, R1 in 11%, and R2 in 3%. Overall survival was 78, 42, and 31% at 1, 5, and 10 years, respectively. Unlike single-institution studies, in this worldwide collaboration, survival progressively decreases and is distinctively stratified by all variables except region of the world. A worldwide esophageal cancer database has been assembled that overcomes problems of rarity of this cancer. It reveals that survival progressively (monotonically) decreased and was distinctively stratified by all variables except region of the world. Thus, it forms the basis for data-driven esophageal cancer staging. More centers are needed and encouraged to join WECC.

The ostrich (Struthio camelus) blastoderm and embryo development following storage of eggs at various temperatures.

1. The gross morphology of blastoderms in fresh unstored ostrich eggs and in eggs subjected to different regimen of storage and incubation was studied. Then the effects of storage duration of eggs (1, 2 and 3 weeks) and storage temperature (15, 20 and 25 degrees C) on blastoderm and embryo development were investigated.2. Only incubation following overnight storage at 18 degrees C advanced blastoderm development (1.5-fold increase in diameter) to a stage comparable to hypoblast. 3. Storage of eggs at 15 or 20 degrees C did not affect blastoderm stage and size whereas, at 25 degrees C, the blastoderm doubled in size and appeared to have advanced to a primitive streak stage. Embryo development was reduced after 2 weeks of storage regardless of the storage temperature. 4. After oviposition and during pre-incubation storage the ostrich blastoderm develops progressively over time in a temperature-dependent manner towards the hypoblast stage and beyond but the viability of the blastoderm and embryo development is seriously compromised by 2 weeks of storage.

An epidemic of salmonellosis caused by Salmonella Typhimurium DT160 in wild birds and humans in New Zealand.

AIM: This study reports an outbreak of salmonellosis due to S. Typhimurium DT160 which caused extensive mortality in wild birds and enteric disease in humans in New Zealand during the winter and spring months of the year 2000. METHODS: Necropsies were performed and microbiological examinations undertaken on wild birds from populations in which mass mortality was reported, and on captive indigenous birds which died suddenly during the winter and spring of 2000. Affected tissues were examined histologically and isolates of S. Typhimurium were phage typed and examined using pulsedfield gel electrophoresis (PFGE). Isolates of S. Typhimurium obtained from cases of human enteric disease which occurred during these months were phage typed, examined using PFGE and compared with the bird isolates. RESULTS: Central and northern areas of the South Island and the southern North Island were worst affected with die-offs of several hundreds of sparrows and other birds reported in rural areas. Mortalities reached a peak in winter (July-August) 2000 and decreased to small numbers during the spring and early summer. The birds usually died of an acute septicaemia with multifocal necrotising lesions in the liver and spleen. Human cases throughout the country increased gradually over the same period. Isolates from birds, livestock and humans examined using PFGE were indistinguishable from one another. CONCLUSION: This strain of Salmonellahas emerged as a major cause of septicaemia in wild birds in New Zealand. Because of the close association between house sparrows (Passer domesticus) and humans, the organism also poses a serious zoonotic risk. The possibility that the infection may spread to involve indigenous species needs investigation.

The utility of EUS and EUS-guided fine needle aspiration in detecting celiac lymph node metastasis in patients with esophageal cancer: a single-center experience.

BACKGROUND: The aims of this study were to determine the utility of EUS and EUS-guided fine needle aspiration (EUS-FNA) in the detection and confirmation of celiac lymph node metastasis in patients with esophageal cancer and to define EUS features predictive of celiac lymph node metastasis in these patients. METHODS: The records of 211 patients with esophageal cancer who underwent EUS staging were reviewed. The operating characteristics of EUS were determined in patients where either surgery, EUS-FNA of a celiac lymph node, or both were performed (n = 102). The association between selected variables and the presence of celiac lymph node metastasis was evaluated by univariate and multivariable analyses. RESULTS: EUS in 48 patients provided a true-positive diagnosis of celiac lymph node involvement, a false-positive and false-negative result, respectively, in 6 and 14 patients, and a true-negative diagnosis in 34 patients. The sensitivity of EUS in detecting celiac lymph node was 77% (95% CI [67, 88]), specificity 85% (95% CI [74, 96]), negative predictive value 71% (95% CI [58, 84]), and the positive predictive value 89% (95% CI [81, 97]). EUS-FNA was performed in 94% (51/54) of patients with celiac lymph nodes. The accuracy of EUS-FNA in detecting malignant celiac lymph nodes was 98% (95% CI [90, 100]). Advanced T-stage, the need for dilation, detection of peritumoral lymph nodes, and black race were associated with celiac lymph node involvement. In multivariable analysis, advanced T-stage was the strongest predictor of celiac lymph node involvement. CONCLUSION: EUS and EUS-FNA are highly accurate in detecting and confirming celiac lymph nodes metastasis. Depth of tumor invasion as assessed by EUS is a strong predictor of celiac lymph node metastasis in patients with esophageal cancer.

Hypersensitivity pneumonitis: current concepts and future questions.

Hypersensitivity pneumonitis (extrinsic allergic alveolitis) caused by inhaled allergens can progress to disabling or even fatal end-stage lung disease. The only truly effective treatment is early recognition and control of exposure. Although patients produce antibody exuberantly, the immunopathogenesis involves cellular immunity--notably, CD8(+) cytotoxic lymphocytes, multinucleate giant cell granulomas, and ultimately interstitial fibrosis. Many causative agents have been recognized in occupational dusts or mists, but most current new cases arise from residential exposure to pet birds (pigeons and parakeets), contaminated humidifiers, and indoor molds. The symptoms and physical findings are nonspecific. Serum IgG containing high titers of specific antibody to the offending antigen is elevated. Pulmonary function tests show restrictive and diffusion defects with hypoxemia, especially after exercise. Occasionally, small airways disease causes obstruction. Radio-graphic changes vary according to the stage of the disease and are best evaluated by means of high-resolution computed tomography. In typical cases, the history of a known exposure and the presence of a characteristic interstitial lung disease with serologic confirmation of IgG antibody to the offending antigen suffice for diagnosis. In more obscure cases, observation of changes after a natural environmental exposure, bronchoalveolar lavage, and lung biopsy might be indicated. Among the many questions that remain are the following: What is the prevalence of hypersensitivity pneumonitis and how often is it the cause of chronic interstitial fibrosis? What is the long-term prognosis? Why do most individuals exposed to these antigens develop a vigorous antibody response whereas only a few develop the disease? How does exposure to endotoxin and cigarette smoking affect the disease? To answer these questions, standardized and validated clinical laboratory immunochemical tests are needed, in addition to a systematic approach to diagnosis, classification of disease severity, risk assessment, and management. This review is limited to the disease caused by airborne allergens and focuses on its immunopathogenesis, eliciting agents, clinical manifestations, diagnosis, management, and prognosis.

Tumor marker expression is predictive of survival in patients with esophageal cancer.

BACKGROUND: This study was designed to determine the prognostic value of immunohistochemical tumor marker expression in a population of patients with node-negative esophageal cancer treated with complete resection alone. METHODS: Resection specimens were collected from 61 patients with node-negative T1 (n = 31), T2 (n = 14), and T3 (n = 16) esophageal cancer. A panel of 10 tumor markers was chosen for immunohistochemical analysis, based on associations with differing oncologic mechanisms: apoptosis (p53), growth regulation (transforming growth factor-alpha, epidermal growth factor receptor, and Her2-neu), angiogenesis (factor VIII), metastatic potential (CD44), platinum resistance (p-glycoprotein and metallothionein), 5-fluorouracil resistance (thymidylate synthetase), and carcinogenic detoxification (glutathione S-transferase-pi). RESULTS: Complete resection was performed in all patients (44 adenocarcinoma, 17 squamous cell carcinoma), with no operative deaths. Multivariable analysis demonstrated a significant relationship between cancer-specific death and the following variables: low-level P-gp expression (p = 0.004), high-level expression of p53 (p = 0.04), and low-level expression of transforming growth factor-alpha (p = 0.03). In addition, the number of involved tumor markers present was strongly predictive of negative outcome (p = 0.0001). CONCLUSIONS: This study supports the prognostic value of immunohistochemical tumor markers, specifically the expression pattern of P-gp, p53, and transforming growth factor-alpha, in patients with esophageal carcinoma treated with complete resection alone.

Endotoxin-stimulated innate immunity: A contributing factor for asthma.

Exposure to airborne endotoxin in infancy may protect against asthma by promoting enhanced T(H)1 response and tolerance to allergens. On the other hand, later in life, it adversely affects patients with asthma. Endotoxin binding to receptors on macrophages and other cells generates IL-12, which inhibits IgE responses. It also generates cytokines like IL-1, TNF-alpha, and IL-8, which cause inflammation. These signal transduction pathways resemble those leading to the generation of cytokines, such as IL-4, IL-13, and IL-5, which are responsible for the inflammation of IgE-mediated allergic disease. The main difference seems to be that endotoxin recruits neutrophils, but IgE recruits eosinophils, and the details of the tissue injury from these granulocytes differ. Sources of airborne endotoxin include many agricultural dusts, aerosols from contaminated water in many industrial plants, contaminated heating and air-conditioning systems, mist-generating humidifiers, and damp or water-damaged homes. Acute inhalation of high concentrations of endotoxin can cause fever, cough, and dyspnea. Chronic inhalation of lesser amounts causes chronic bronchitis and emphysema and is associated with airway hyperresponsiveness. Airborne endotoxin adversely affects patients with asthma in 3 ways: (1) by increasing the severity of the airway inflammation; (2) by increasing the susceptibility to rhinovirus-induced colds; and (3) by causing chronic bronchitis and emphysema with development of irreversible airway obstruction after chronic exposure of adults. The most effective management is mitigating exposure. The potential of drug treatments requires further clinical investigation.

Predictors of survival for esophageal cancer patients with and without celiac axis lymphadenopathy: impact of staging endosonography.

BACKGROUND: Esophageal cancer patients with M1a disease are reported to have poor survival. We hypothesized that patients with celiac lymph node metastases (CLN) identified by endoscopic ultrasonography (EUS) would predict a cohort with significantly worse survival postoperatively. Accurate preoperative identification of this group will facilitate future adjuvant studies. METHODS: During the study period, 211 patients with esophageal cancer underwent EUS staging. Patients with evaluable celiac axis (n = 182) were included in this study. Survival of patients with and without CLNs was compared and the factors affecting overall survival were assessed. A subgroup analysis based on CLN status was performed in the subgroup of patients who underwent surgical procedures. RESULTS: Follow-up data was available in 91.2% (166 of 182) of the patients. As staged by EUS, T1, T2, T3, and T4 tumors accounted for 9.3%, 11.5%, 56%, and 21% of the cases, respectively. At least one CLN was imaged by EUS in 40% (72 of 182). The 5-year survival in patients with CLNs detected by EUS was 13% (95% confidence interval, 5% to 21%) compared with 30% (95% confidence interval, 21% to 40%) in patients with no CLNs detected by EUS (p = 0.007). In the subgroup of patients who underwent surgical procedures (n = 68), patients with CLN involvement had worse survival compared with those who did not have malignant involvement of CLNs at the time of their operation (median survival 39.8 versus 13.8 months, p = 0.0008). In a Cox proportional model, adjusting for race and the type of therapy, patients with CLN involvement or advanced EUS American Joint Committee on Cancer stage were more likely to have worse survival (p < 0.05) CONCLUSIONS: EUS base line findings correlate with long term survival in patients with esophageal cancer. Patients with M1a disease as identified by EUS had a significantly worse postoperative survival when compared with non-M1a patients. This cohort of patients will be ideal for the study of induction therapy since the effect of down staging can be assessed before operation.

CALGB 9380: a prospective trial of the feasibility of thoracoscopy/laparoscopy in staging esophageal cancer.

BACKGROUND: The staging of esophageal cancer is imprecise. Thoracoscopic/laparoscopic (TS/LS) staging has been proposed as a more accurate lymph node (LN) staging method. We report the experience of an Intergroup NCI trial (CALGB 9380) evaluating the feasibility and accuracy of this staging modality. PATIENTS AND METHODS: From February 1995 to September 1999, 134 patients were entered in the study. This study represents the analysis of final data on 113 patients. TS/LS was considered feasible if TS and 1 LN sampled at least 3 LN by LS; a confirmed positive node was found; or T4 or M1 disease was documented. If this was accomplished in more than 70% of patients, TS/LS was believed to be feasible. RESULTS: The LN stations most frequently sampled in the thorax (134 patients) were levels 2 (33%), 3 (38%), 4 (40%), 7 (76%), 8 (69%), 9 (55%), and 10 (43%) and in the abdomen levels 17 (70%) and 20 (55%). The frequency of positive LN by level were as follows: 2 (10%), 3 (8%), 4 (10%), 7 (10%), 8 (25%), 9 (10%), 10 (10%), 17 (34%), and 20 (27%). Noninvasive tests (computed tomographic scan, magnetic resonance imaging, esophageal ultrasound scan) each incorrectly identified TN staging as noted by missed positive or false-negative LN or metastatic disease found at TS/LS staging in 50%, 40%, and 30% of patients, respectively. Median operating time was 210 minutes (range, 40 to 865 minutes). Median postoperative hospital stay was 3 days (range, 1 to 35 days). There were no deaths or major complications. Seventy-three percent of patients met the definition for feasibility. In 30 patients TS was not feasible. Positive LN disease was found in 43 patients; 32 were deemed N0. Ten patients had T4/M1 disease. Of the 32 potentially resectable N0 patients, 14 patients had preoperative induction therapy; 13 patients went directly to operation with N0 confirmed in 9 patients, NX in 1 and N1 in 3. Three patients were unresectable, 1 patient died, and 1 was lost to follow-up. CONCLUSIONS: In summary, the feasibility of TS/LS was confirmed. It doubled the number of positive LNs identified by conventional, noninvasive staging. The overall accuracy remains to be defined by analysis of the LN negative group in follow-up. Although the positive predictive value was high, further study is warranted to confirm the role of TS/LS in the staging algorithm of esophageal cancer.

The 30th anniversary of the American Board of Allergy and Immunology: then and now.

Thirty years ago the Allergy Subspecialty Boards of the American Board of Pediatrics (ABP) and the American Board of Internal Medicine (ABIM) merged to form the American Board of Allergy and Immunology (ABAI). The ABAI mission was to: establish qualifications and examine physician candidates for certification as specialists in allergy and immunology; serve the public, physicians, hospitals, and medical schools by providing the names of physicians certified by the Board; assist educational and professional organizations to improve the quality of care and availability of allergists to deliver such care, to establish and improve standards for the teaching of allergy and immunology, to establish standards for training programs, and to encourage development of increased opportunities for training of physicians interested in allergy and immunology. This mission statement has guided the activities of the Board ever since by providing a strong focus on the 2 major responsibilities: examining and certifying candidates in a fair objective way, and setting standards for the content and conduct of training programs.

Endoscopic ultrasound-guided fine needle aspiration for staging patients with carcinoma of the lung.

BACKGROUND: Endoscopic ultrasound (EUS)-guided fine needle aspiration is a safe, cost-effective procedure that can confirm the presence of mediastinal lymph node metastases and mediastinal tumor invasion. We studied the accuracy of EUS in a large population of lung cancer patients with and without enlarged mediastinal lymph nodes on computed tomographic (CT) scan. METHODS: From 1996 to 2000 all patients referred to our institution with lung tumors and no proven distant metastases were considered for EUS and surgical staging. Patients had endoscopic ultrasound with fine needle aspiration of abnormal appearing mediastinal lymph nodes and evaluation for mediastinal invasion of tumor (stage III or IV disease). Patients without confirmed stage III or IV disease had surgical staging. RESULTS: Two hundred seventy-seven patients met the inclusion criteria, including 121 who had EUS. Endoscopic ultrasound and fine needle aspiration detected stage III or IV disease in 85 of 121 (70%). Among patients with enlarged lymph nodes on CT, 75 of 97 (77%) had stage III or IV disease detected by EUS. Among a small cohort of patients without enlarged mediastinal lymph nodes on CT, 10 of 24 (42%) had stage III or IV disease detected by EUS. For mediastinal lymph nodes only, the sensitivity of endoscopic ultrasound and CT was 87%. The specificity of EUS (100%) was superior to that of CT (32%) (p < 0.001). CONCLUSIONS: Endoscopic ultrasound with fine needle aspiration identified and histologically confirmed mediastinal disease in more than two thirds of patients with carcinoma of the lung who have abnormal mediastinal CT scans. Although mediastinal disease was more likely in patients with an abnormal mediastinal CT, EUS also detected mediastinal disease in more than one third of patients with a normal mediastinal CT and deserves further study. Endoscopic ultrasound should be considered a first line method of presurgical evaluation of patients with tumors of the lung.

Mechanism of topical glucocorticoid treatment of hay fever: IL-5 and eosinophil activation during natural allergen exposure are suppressed, but IL-4, IL-6, and IgE antibody production are unaffected.

BACKGROUND: Allergic rhinitis is traditionally defined as an IgE- and mast cell-mediated hypersensitivity reaction. Allergen challenge models suggest that cytokines and eosinophil mediators may also play roles. However, the causal relationship among inflammatory cells, their products, and patients' symptoms during natural allergen exposure has not been established. OBJECTIVE: We sought to elucidate the mechanisms of seasonal allergic rhinitis and the beneficial effects of topical glucocorticoids. METHODS: Thirty patients with ragweed-induced hay fever and a strongly positive serologic test response for ragweed IgE antibody received budesonide nasal spray or placebo in a randomized, parallel, double-blind study. Nasal wash fluids and sera were collected before and during the hay fever season. The levels of inflammatory mediators and allergen-specific immunoglobulins were measured by immunoassay. The activation markers on blood eosinophils were quantitated by flow cytometry. RESULTS: Compared with placebo-treated patients, budesonide-treated patients had strikingly reduced symptoms. In the placebo group, nasal symptoms correlated with nasal lavage fluid eosinophil-derived neurotoxin and IL-5 levels. At the season peak, the budesonide-treated group had significantly lower nasal fluid eosinophil-derived neurotoxin, IL-5, and soluble intracellular adhesion molecule-1 levels. In the treated group eosinophil expression of CD11b was suppressed at the season peak. In contrast, levels of IL-4 and IL-6 in nasal fluid and the seasonal increases in serum ragweed-specific IgE and nasal fluid IgA antibodies did not differ between groups. CONCLUSION: Eosinophilic inflammation plays a critical role in seasonal allergic rhinitis symptoms. One of the therapeutic effects of glucocorticoids is to suppress this inflammation.

Cost-efficacy of endoscopic ultrasonography with fine-needle aspiration vs. mediastinotomy in patients with lung cancer and suspected mediastinal adenopathy.

BACKGROUND AND STUDY AIMS: The use of endoscopic ultrasonography (EUS) guidance for fine-needle aspiration (FNA) of mediastinal lymph nodes has become an important aid in the staging of bronchogenic carcinoma. In many cases, it may be an alternative to mediastinoscopy/mediastinotomy (MED), but the cost-effectiveness of the two techniques has not been compared. The aim of this study was to apply a decision-analysis model to compare the cost-effectiveness of EUS and MED in the preoperative staging of patients with non-small-cell lung cancer. PATIENTS AND METHODS: A decision-analysis model was designed, taking as entry criteria lung cancer and abnormal mediastinal lymph nodes verified by computerized tomography (CT). Performance characteristics of MED and EUS were retrieved from the published literature, as were life expectancy data. Direct actual costs of the relevant procedures were retrieved from the billing system of our hospital. RESULTS: The cost per year of expected survival is US$ 1.729 with the EUS strategy, and US$ 2.411 with the MED strategy. The advantage conferred by EUS remains even when the negative predictive value of EUS is as low as 0.22. CONCLUSION: Because of its low cost and high yield, EUS-guided FNA is a cost-effective aid assessing mediastinal lymphadenopathy.

Lung cancer staging and treatment in multidisciplinary trials: Cancer and Leukemia Group B cooperative group approach. Thoracic Surgeons of CALGB.

BACKGROUND: Aggressive routine surgical staging is necessary to evaluate patients to be treated on cooperative oncology protocols. Less than 1% of lung cancer patients in the United States are currently being treated in a clinical trial. Only with results from large, prospective trials can the questions of neoadjuvant and adjuvant therapy be answered. METHODS: An outline describing the schema of preoperative patient evaluation, surgical staging, and the definition of surgical staging and resection procedures appropriate for patients considered for cooperative group protocol is presented. Current Cancer and Leukemia Group B (CALGB) protocols are used in the discussion as examples of this systematic approach. CONCLUSIONS: Over the next few years, it will be important to enter the maximum number of patients into combined modality studies to identify the role of neoadjuvant treatment in lung cancer. Entry of patients into protocols will also make their pathological specimens and clinical information available for basic science research related to treatment results. Adherence to a logical sequence of patient evaluation as outlined above will optimize patient care, as well as accrual to cooperative group studies.

Does IgE bind to and activate eosinophils from patients with allergy?

Human eosinophils have been reported to express both the mRNA and protein for the high affinity IgE receptor (FcepsilonRI); it is speculated that this receptor plays a role in eosinophil mediator release in allergic diseases. However, questions still remain. How much of the FcepsilonRI protein is actually expressed on the cell surface of the eosinophil? If they are present, are these IgE receptors associated with effector functions of eosinophils? To address these issues, we studied blood eosinophils from patients with ragweed hay fever. A high level of low affinity IgG receptor (FcgammaRII, CD32), but no expression of FcepsilonRI, was detectable on the eosinophil surface by standard FACS analysis. However, after in vitro sensitization with biotinylated chimeric IgE (cIgE), cell-bound cIgE was detected by PE-conjugated streptavidin. This cIgE binding was partially inhibited by anti-FcepsilonRI mAb, suggesting that eosinophils do express minimal amounts of FcepsilonRI detectable only by a sensitive method. Indeed, FACS analysis of whole blood showed that eosinophils express approximately 0.5% of the FcepsilonRI that basophils express. When stimulated with human IgE or anti-human IgE, these eosinophils did not exert effector functions; there was neither production of leukotriene C4 or superoxide anion nor any detectable degranulation response. In contrast, eosinophils possessed membrane-bound human IgG and showed functional responses when stimulated with human IgG or anti-human IgG. Thus, IgG and/or cytokines, such as IL-5, appear to be more important for eosinophil activation in allergic diseases than IgE.

Physiologic consequences of pneumonectomy. Consequences on the pulmonary function.

The cardiac sequelae following pneumonectomy should be anticipated by a thorough preoperative evaluation of cardiac risk factors, and any identified significant risk should be evaluated and corrected. The most common cardiac complication following pneumonectomy is atrial dysrhythmia. The possible causes, significant correlates, and rationale for prophylaxis are discussed. With a large portion of the pulmonary vascular bed removed by pneumonectomy, the possibility and consequences of right ventricular dysfunction are outlined. Finally, the rare but catastrophic occurrence of cardiac herniation is described.