Routine HIV Screening in Cancer Patients in the Emergency Department.

Treatment of human immunodeficiency virus(HIV) in cancer patients improves outcomes and reduces transmission of this oncogenic virus. HIV testing rates of cancer patients are similar to the general population (15-40%), despite the association with cancer. Our aim was to increase HIV screening in the Emergency Department(ED) of a comprehensive cancer center through a quality initiative. Testing increased significantly during the intervention (p<0.001; 0.15/day to 2.69/day). Seropositive HIV rate was 1.4% (12/852), with incidence of 0.3%. All patients were linked to care. Incident cases were between 36 and 55 years of age. Barriers encountered included confusion regarding the need for written consent for HIV testing, failure to consider ordering the test, and concerns regarding linkage to care.

Recommendations for pathologic staging (pTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals.

We report analytic and consensus processes that produced recommendations for pathologic stage groups (pTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration provided data for 22,654 patients with epithelial esophageal cancers; 13,300 without preoperative therapy had pathologic assessment after esophagectomy or endoscopic treatment. Risk-adjusted survival for each patient was developed using random survival forest analysis to identify data-driven pathologic stage groups wherein survival decreased monotonically with increasing group, was distinctive between groups, and homogeneous within groups. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced consensus pathologic stage groups. For pT1-3N0M0 squamous cell carcinoma (SCC) and pT1-2N0M0 adenocarcinoma, pT was inadequate for grouping; subcategorizing pT1 and adding histologic grade enhanced staging; cancer location improved SCC staging. Consensus eliminated location for pT2N0M0 and pT3N0M0G1 SCC groups, and despite similar survival, restricted stage 0 to pTis, excluding pT1aN0M0G1. Metastases markedly reduced survival; pT, pN, and pM sufficiently grouped advanced cancers. Stage IIA and IIB had different compositions for SCC and adenocarcinoma, but similar survival. Consensus stage IV subgrouping acknowledged pT4N+ and pN3 cancers had poor survival, similar to pM1. Anatomic pathologic stage grouping, based on pTNM only, produced identical consensus stage groups for SCC and adenocarcinoma at the cost of homogeneity in early groups. Pathologic staging can neither direct pre-treatment decisions nor aid in prognostication for treatment other than esophagectomy or endoscopic therapy. However, it provides a clean, single therapy reference point for esophageal cancer.

Worldwide Esophageal Cancer Collaboration: pathologic staging data.

We report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for patients with pathologically staged cancer of the esophagus and esophagogastric junction after resection or ablation with no preoperative therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted de-identified data using standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 13,300 patients, 5,631 had squamous cell carcinoma, 7,558 adenocarcinoma, 85 adenosquamous carcinoma, and 26 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (51%), little weight loss (1.8 kg), 0-2 ECOG performance status (83%), and a history of smoking (70%). Cancers were pT1 (24%), pT2 (15%), pT3 (50%), pN0 (52%), pM0 (93%), and pG2-G3 (78%); most involved distal esophagus (71%). Non-risk-adjusted survival for both squamous cell carcinoma and adenocarcinoma was monotonic and distinctive across pTNM. Survival was more distinctive for adenocarcinoma than squamous cell carcinoma when pT was ordered by pN. Survival for pTis-1 adenocarcinoma was better than for squamous cell carcinoma, although monotonic and distinctive for both. WECC pathologic staging data is improved over that of the 7th edition, with more patients studied and patient and cancer variables collected. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics, and should direct 9th edition data collection. However, the role of pure pathologic staging as the principal point of reference for esophageal cancer staging is waning.

Worldwide Esophageal Cancer Collaboration: clinical staging data.

To address uncertainty of whether clinical stage groupings (cTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for clinically staged patients from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 22,123 clinically staged patients, 8,156 had squamous cell carcinoma, 13,814 adenocarcinoma, 116 adenosquamous carcinoma, and 37 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (18.5-25 mg/kg2 , 47%), little weight loss (2.4 ± 7.8 kg), 0-1 ECOG performance status (67%), and history of smoking (67%). Cancers were cT1 (12%), cT2 (22%), cT3 (56%), cN0 (44%), cM0 (95%), and cG2-G3 (89%); most involved the distal esophagus (73%). Non-risk-adjusted survival for squamous cell carcinoma was not distinctive for early cT or cN; for adenocarcinoma, it was distinctive for early versus advanced cT and for cN0 versus cN+. Patients with early cancers had worse survival and those with advanced cancers better survival than expected from equivalent pathologic categories based on prior WECC pathologic data. Thus, clinical and pathologic categories do not share prognostic implications. This makes clinically based treatment decisions difficult and pre-treatment prognostication inaccurate. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient characteristics, cancer categories, and treatment characteristics and should direct 9th edition data collection.

Worldwide Esophageal Cancer Collaboration: neoadjuvant pathologic staging data.

To address uncertainty of whether pathologic stage groupings after neoadjuvant therapy (ypTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for pathologically staged cancers after neoadjuvant therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 7,773 pathologically staged neoadjuvant patients, 2,045 had squamous cell carcinoma, 5,686 adenocarcinoma, 31 adenosquamous carcinoma, and 11 undifferentiated carcinoma. Patients were older (61 years) men (83%) with normal (40%) or overweight (35%) body mass index, 0-1 Eastern Cooperative Oncology Group performance status (96%), and a history of smoking (69%). Cancers were ypT0 (20%), ypT1 (13%), ypT2 (18%), ypT3 (44%), ypN0 (55%), ypM0 (94%), and G2-G3 (72%); most involved the distal esophagus (80%). Non-risk-adjusted survival for yp categories was unequally depressed, more for earlier categories than later, compared with equivalent categories from prior WECC data for esophagectomy-alone patients. Thus, survival of patients with ypT0-2N0M0 cancers was intermediate and similar regardless of ypT; survival for ypN+ cancers was poor. Because prognoses for ypTNM and pTNM categories are dissimilar, prognostication should be based on separate ypTNM categories and groupings. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics and should direct 9th edition data collection.

Timed barium esophagram in achalasia types.

Relationships of timed barium esophagram (TBE) findings to achalasia types defined by high-resolution manometry (HRM) have not been elucidated. Therefore, we correlated preoperative TBE and HRM measurements in achalasia types and related these to patient symptoms and prior treatments. From 2006 to 2013, 248 achalasia patients underwent TBE and HRM before Heller myotomy. TBE height and width were recorded at 1 and 5 minutes; HRM measured lower esophageal sphincter mean basal pressure, integrated relaxation pressure (IRP), and mean esophageal body contraction amplitude. Achalasia was classified into types I (25%), II (65%), and III (9.7%). TBE height at 5 minutes was higher for I (median 8 cm; interquartile range 6-12) and II (8 cm; 8-11) than for III (1 cm; 0-7). TBE width at 5 minutes was widest (3 cm; 2-4), narrower in II (2 cm; 2-3), and narrowest in I (1 cm; 0-2), P < 0.001. Volume remaining at 1 and 5 minutes was lower in III (1 m(2) ; 0-16) than I (42 m(2) ; 17-106) and II (39 m(2) ; 15-60), highlighting poorer emptying of I and II. Increasing TBE width correlated with deteriorating morphology and function from III to II to I. Symptoms poorly correlated with TBE and HRM. Prior treatment was associated with less regurgitation, faster emptying, and lower IRP. Although TBE and HRM are correlated in many respects, the wide range of their measurements observed in this study reveals a spectrum of morphology and dysfunction in achalasia that is best characterized by the combination of these studies.

Gefitinib in definitive management of esophageal or gastroesophageal junction cancer: a retrospective analysis of two clinical trials.

The role of epidermal growth factor receptor inhibition in resectable esophageal/gastroesophageal junction (E/GEJ) cancer is uncertain. Results from two Cleveland Clinic trials of concurrent chemoradiotherapy (CCRT) and surgery are updated and retrospectively compared, the second study differing only by the addition of gefitinib (G) to the treatment regimen. Eligibility required a diagnosis of E/GEJ squamous cell or adenocarcinoma, with an endoscopic ultrasound stage of at least T3, N1, or M1a (American Joint Committee on Cancer 6th). Patients in both trials received 5-fluorouracil (1000 mg/m(2) /day) and cisplatin (20 mg/m(2) /day) as continuous infusions over days 1-4 along with 30 Gy radiation at 1.5 Gy bid. Surgery followed in 4-6 weeks; identical CCRT was given 6-10 weeks later. The second trial added G, 250 mg/day, on day 1 for 4 weeks, and again with postoperative CCRT for 2 years. Preliminary results and comparisons have been previously published. Clinical characteristics were similar between the 80 patients on the G trial (2003-2006) and the 93 patients on the no-G trial (1999-2003). Minimum follow-up for all patients was 5 years. Multivariable analyses comparing the G versus no-G patients and adjusting for statistically significant covariates demonstrated improved overall survival (hazard ratio [HR] 0.64, 95% confidence interval [CI] = 0.45-0.91, P = 0.012), recurrence-free survival (HR 0.61, 95% CI = 0.43-0.86, P = 0.006), and distant recurrence (HR 0.68, 95% CI = 0.45-1.00, P = 0.05), but not locoregional recurrence. Although this retrospective comparison can only be considered exploratory, it suggests that G may improve clinical outcomes when combined with CCRT and surgery in the definitive treatment of E/GEJ cancer.

Esophageal leiomyoma: experience from a single institution.

Esophageal leiomyomas are rare. We report the clinicopathologic features of one of the largest series of esophageal leiomyomas from a single institution. We retrospectively reviewed the Cleveland Clinic pathology database (1985-2010) for patients with a diagnosis of esophageal leiomyoma(s). Clinicopathologic features of 30 cases from 28 patients were analyzed. The group included 15 females and 13 males with a mean age at diagnosis of 56 years. These include 9 excisions, 9 esophagectomies, and 12 endoscopic biopsies. Only one partial esophagectomy was performed solely for a symptomatic 14-cm leiomyoma; the remainder of the resections (n= 8) were for other indications, including esophageal cancer (Barrett's esophagus-related adenocarcinoma and squamous cell carcinoma) and emergent esophageal perforation, with leiomyoma being an incidental finding. One patient (2.5%) had two synchronous leiomyomas (14 cm and 0.3 cm). Tumor size ranged from 0.1 to 14 cm (mean = 2.0 cm). Mean tumor size among symptomatic patients was 5.2 cm, as compared with 0.4 cm in asymptomatic patients. Dysphagia was the most common complaint in symptomatic patients (71.4%). Sixty-nine percent of the tumors were located in the distal and middle thirds of the esophagus, with most (69.6%) arising from muscularis propria. Histologically, these tumors were composed of bland spindle cells with low cellularity, no nuclear atypia, or mitotic activity. Only one case (14 cm) showed focal moderate cellularity and nuclear atypia, with low mitotic activity (<1/10 high power field). Immunohistochemical studies showed tumor cells were positive for smooth muscle actin, and negative for CD34 and CD117. Follow-up information was available for 22 patients (78.6%), and none had adverse events related to leiomyoma. In summary, esophageal leiomyoma is a rare benign tumor of the esophagus. Patients with larger tumors were more likely to have symptoms. The majority of the tumors were in the lower and mid-esophagus, and arose from muscularis propria. These tumors behave in a clinically benign fashion.

Esophageal small-cell cancer: study of a rare disease.

Optimal treatment of esophageal small-cell cancer, a rare disease, lacks consensus. Based on its lung small-cell cancer analog, we hypothesized that chemotherapy with adjuvant radiotherapy would be optimal. This hypothesis was tested by studying the collective published literature. A meta-analysis of individual patients from 148 articles (1952-2010) explored treatment and outcome of 577 patients with esophageal small-cell cancer. Hazard function frailty modeling identified optimum therapy after accounting for article-level and patient-level heterogeneity. Fifty-nine percent of publications reported one patient and 25% five or more. Sixty-six percent of patients were men, mean age was 63 ± 11 years, and 64% had localized disease. One, 3-, and 5-year survival was 37%, 14%, and 11%, respectively. Survival variation among articles was substantial (P = 0.004), with survival improving across time (P < 0.0004). Chemotherapy was associated with better survival (hazard ratio [HR] = 0.53, 68% confidence interval [CI] = 0.44-0.65; P = 0.002) than surgery alone, radiotherapy alone, nonstandard therapy, or no therapy. Adding local therapy, either surgery (HR = 0.41, 68% CI = 0.34-0.51; P < 0.0001) or radiotherapy (HR = 0.33, 68% CI = 0.27-0.41; P < 0.0001), to chemotherapy further improved survival. Adding both did not provide further benefit. The strategy of borrowing from consensus treatment of lung small-cell cancer and analyzing the scarce available esophageal small-cell cancer literature may be beneficial in the study of rare diseases. It confirmed that chemotherapy should be the mainstay of therapy, with additional benefit from adjuvant therapy with either surgery or radiotherapy; both are not needed.

Clinicopathologic features and treatment outcomes of patients with human epidermal growth factor receptor 2-positive adenocarcinoma of the esophagus and gastroesophageal junction.

Human epidermal growth factor receptor 2 (HER2) is overexpressed in 21% of gastric and 33% of gastroesophageal junction (GEJ) adenocarcinomas. Trastuzumab has been approved for metastatic HER2-positive gastric/GEJ cancer in combination with chemotherapy. This retrospective analysis was undertaken to better define the clinicopathologic features, treatment outcomes, and prognosis in patients with HER2-positive adenocarcinoma of the esophagus/GEJ. Pathologic specimens from 156 patients with adenocarcinoma of the esophagus/GEJ treated on clinical trials with chemoradiation and surgery were tested for HER2. Seventy-six patients also received 2 years of gefitinib. Baseline characteristics and treatment outcomes of the HER2-positive and negative patients were compared both in aggregate and separately for each of the two trials. Of 156 patients, 135 had sufficient pathologic material available for HER2 assessment. HER2 positivity was found in 23%; 28% with GEJ primaries and 15% with esophageal primaries (P= 0.10). There was no statistical difference in clinicopathologic features between HER2-positive and negative patients except HER2-negative tumors were more likely to be poorly differentiated (P < 0.001). Locoregional recurrence, distant metastatic recurrence, any recurrence, and overall survival were also statistically similar between the HER2-positive and the HER2-negative groups, in both the entire cohort and in the gefitinib-treated subset. Except for tumor differentiation, HER2-positive and negative patients with adenocarcinoma of the esophagus and GEJ do not differ in clinicopathologic characteristics and treatment outcomes. Given the demonstrated benefit of trastuzumab in HER2-positive gastric cancer and the similar incidence of HER2 overexpression in esophageal/GEJ adenocarcinoma, further evaluation of HER2-directed therapy in this disease seems indicated.

Bedside end-tidal CO2 tension as a screening tool to exclude pulmonary embolism.

End tidal carbon dioxide tension (P(ET,CO(2))) is a surrogate for dead space ventilation which may be useful in the evaluation of pulmonary embolism (PE). We aimed to define the optimal P(ET,CO(2)) level to exclude PE in patients evaluated for possible thromboembolism. 298 patients were enrolled over 6 months at a single academic centre. P(ET,CO(2)) was measured within 24 h of contrast-enhanced helical computed tomography, lower extremity duplex or ventilation/perfusion scan. Performance characteristics were measured by comparing test results with clinical diagnosis of PE. PE was diagnosed in 39 (13%) patients. Mean P( ET,CO(2)) in healthy volunteers did not differ from P( ET,CO(2)) in patients without PE (36.3+/-2.8 versus 35.5+/-6.8 mmHg). P(ET,CO(2 )) in patients with PE was 30.5+/-5.5 mmHg (p<0.001 versus patients without PE). A P(ET,CO(2)) of >or=36 mmHg had optimal sensitivity and specificity (87.2 and 53.0%, respectively) with a negative predictive value of 96.6% (95% CI 92.3-98.5). This increased to 97.6% (95% CI 93.2-99.) when combined with Wells score <4. A P(ET,CO(2)) of >or=36 mmHg may reliably exclude PE. Accuracy is augmented by combination with Wells score. P( ET,CO(2)) should be prospectively compared to D-dimer in accuracy and simplicity to exclude PE.

Open window thoracostomy: modern update of an ancient operation.

INTRODUCTION: In modern day thoracic surgical practice, better understanding of the pathophysiology of intrathoracic infections, improved antibiotic therapy and advancements in thoracic surgical techniques have decreased the use of procedures such as open window thoracostomy (OWT). Despite this, there are occasions where OWT cannot be avoided, and it is of interest where its current utility lies. To determine the current efficacy of OWT, we reviewed our recent experience with a focus on the indications, timing of surgery, effectiveness in clearing infection, patient survival, and timing of closure. METHODS: After Institutional Review Board approval, charts of 78 patients were reviewed. Dates reviewed were from 1/1/1998 to 1/1/2008. Patients were predominantly male (66 %) with a median age 58 years. Median time from initial diagnosis to OWT was 70 days (range 1 to 720 days). RESULTS: Primary indication for surgery was empyema in 75 (96 %), and most patients had previous thoracic surgery. The most frequent causes of empyema were post-pneumonectomy (n = 25), post-pneumonic (n = 14), and post-lobectomy (n = 9). Bronchopleural fistulae were present in 29 (37 %) cases. Lung cancer was diagnosed in 34 (45 %) patients, and 24 underwent perioperative radiation therapy. Patient survival at 1 month, 6 months, 1 year and 5 years was 94 %, 82 %, 74 % and 60 %, respectively, with an in-hospital mortality of 6.4 %. Infection was controlled in nearly all patients (n = 72). Fifteen (19 %) patients underwent surgical closure for OWT; in 2 (2.6 %), OWT closed spontaneously. CONCLUSIONS: Currently, open window thoracostomy is used to treat complex empyema incurred from pulmonary resection, cancer and/or infection in patients that cannot be managed by more conservative strategies. Overall mortality and morbidity rates are acceptable in this debilitated patient group.

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.

Does paclitaxel improve the chemoradiotherapy of locoregionally advanced esophageal cancer? A nonrandomized comparison with fluorouracil-based therapy.

PURPOSE: A phase II trial of accelerated fractionation radiation with concurrent cisplatin and paclitaxel chemotherapy was performed to investigate the role of the paclitaxel, when substituted for fluorouracil (5-FU), in the chemoradiotherapy of esophageal cancer. PATIENTS AND METHODS: Patients with an esophageal ultrasound stage of T(3) or N(1) or M(1) (nodal) esophageal cancer were treated with two courses of a cisplatin infusion (20 mg/m(2)/d for 4 days) and paclitaxel (175 mg/m(2) over 24 hours) concurrent with a split course of accelerated fractionation radiation (1.5 Gy bid to a total dose of 45 Gy). Surgical resection was performed 4 to 6 weeks later followed by a single identical postoperative course of chemoradiotherapy (24 Gy) in patients with significant residual tumor at surgery. Toxicity and results of this treatment were retrospectively compared with our previous 5-FU and cisplatin chemoradiotherapy experience. RESULTS: Between September 1995 and July 1997, 40 patients were entered onto this study. Although dysphagia proved worse in our 5-FU-treated patients, profound leukopenia and a need for unplanned hospitalization were significantly more common in the paclitaxel group. Thirty-seven patients (93%) proved resectable for cure. The 3-year projected overall survival is 30%, locoregional control is 81%, and distant metastatic disease control is 44%. When compared with a similarly staged cohort of 5-FU-treated patients, there was no advantage for any survival function studied. CONCLUSION: This paclitaxel-based treatment regimen for locoregionally advanced esophageal cancer produced increased toxicity with no improvement in results when compared with our previous 5-FU experience. Paclitaxel-based treatments must be carefully and prospectively studied before their incorporation into the standard management of esophageal cancer.

Concurrent cisplatin/etoposide plus chest radiotherapy followed by surgery for stages IIIA (N2) and IIIB non-small-cell lung cancer: mature results of Southwest Oncology Group phase II study 8805.

PURPOSE: To assess the feasibility of concurrent chemotherapy and irradiation (chemoRT) followed by surgery in locally advanced non-small-cell lung cancer (NSCLC) in a cooperative group setting, and to estimate response, resection rates, relapse patterns, and survival for stage subsets IIIA(N2) versus IIIB. PATIENTS AND METHODS: Biopsy proof of either positive N2 nodes (IIIAN2) or of N3 nodes or T4 primary lesions (IIIB) was required. Induction was two cycles of cisplatin and etoposide plus concurrent chest RT to 45 Gy. Resection was attempted if response or stable disease occurred. A chemoRT boost was given if either unresectable disease or positive margins or nodes was found. RESULTS: The median follow-up time for 126 eligible patients [75 stage IIIA(N2) and 51 IIIB] was 2.4 years. The objective response rate to induction was 59%, and 29% were stable. Resectability was 85% for the IIIA(N2) group eligible for surgery and 80% for the IIIB group. Reversible grade 4 toxicity occurred in 13% of patients. There were 13 treatment-related deaths (10%) and 19 others (15%) died of causes not related to toxicity or tumor. Of 65 relapses, 11% were only locoregional and 61% were only distant. There were 26 brain relapses, of which 19 were the sole site or cause of death. There was no survival difference (P = .81) between stage IIIA(N2) versus stage IIIB (median survivals, 13 and 17 months; 2-year survival rates, 37% and 39%; 3-year survival rates, 27% and 24%). The strongest predictor of long-term survival after thoracotomy was absence of tumor in the mediastinal nodes at surgery (median survivals, 30 v 10 months; 3-year survival rates, 44% v 18%; P = .0005). CONCLUSION: This trimodality approach was feasible in this Southwest Oncology Group (SWOG) study, with an encouraging 26% 3-year survival rate. An Intergroup study is currently being conducted to determine whether surgery adds more to the risk or to the benefit of chemoRT.

The nature of the myenteric infiltrate in achalasia: an immunohistochemical analysis.

Achalasia is an esophageal motor disorder characterized by abnormal relaxation of the lower esophageal sphincter and absence of progressive peristalsis in the esophageal body. Previous studies evaluating esophagomyotomy and esophageal resection specimens have shown the presence of myenteric inflammation to be a consistent and early pathologic change in patients with achalasia. Thus, the goal of this study was to determine the immunohistochemical characteristics of the inflammatory infiltrate within the myenteric plexus in patients with clinically early and end-stage achalasia. Using formalin-fixed tissue, we analyzed the immunohistochemical features of the myenteric lymphocytes using antibodies that recognize B cells (CD20), T cells (CD3), T cell subsets (CD8), and the activation state of T cell subpopulations (TIA-1 and granzyme B) in nine patients with clinically early achalasia who underwent esophagomyotomy and 13 patients with clinically endstage achalasia who underwent esophageal resection. The myenteric infiltrate in all nine esophagomyotomy specimens was composed predominantly of T cells (CD3-positive), the majority of which also stained for CD8. In five of nine specimens, the majority of CD8-positive cells stained for TIA-1. In the esophageal resection specimens, the myenteric infiltrate was composed predominantly of CD3-positive T cells in seven of 13 cases. In three cases, there was a predominance of CD20-positive B cells, and in the remaining three cases there were relatively equal numbers of T and B cells. In eight of 13 cases, the majority of T cells stained for CD8. TIA-1 immunoreactivity was found in the majority of CD8-positive cells in nine of 13 cases. In all esophagomyotomy and esophageal resection specimens studied, rare granzyme B-positive cells were detected. In conclusion, the majority of myenteric inflammatory cells in patients with achalasia are CD3-positive T cells, most of which are also CD8-positive, although the relative percentage of such cells appears to decrease with disease progression. Furthermore, many of the CD3-positive/CD8-positive myenteric lymphocytes also express TIA-1, suggesting they are resting or activated cytotoxic T cells. The immunohistochemical demonstration of granzyme B in a subpopulation of these cells supports the contention that achalasia is an immune-mediated disease, although the inciting antigen remains an enigma.

Squamous mucosal alterations in esophagectomy specimens from patients with end-stage achalasia.

Achalasia is an esophageal motor disorder in which the primary morphologic changes are found in the myenteric plexus. However, a number of secondary alterations are characteristically found in esophagectomy specimens, including the mucosa. In addition, these patients are at increased risk of developing esophageal squamous cell carcinoma. We studied the squamous mucosal alterations in 35 esophagectomy specimens from patients with end-stage achalasia and compared them with those found in the squamous mucosa near the esophagogastric junction from pediatric autopsies (

Epithelioid angiosarcoma of the pulmonary artery.

Pulmonary artery angiosarcoma is a rare entity. We report a case of an epithelioid angiosarcoma developing from the right pulmonary artery with pulmonary parenchymal invasion. The patient was a 69-year-old man who presented with massive hemoptysis and shortness of breath. Right middle and lower lobectomies were performed because of uncontrollable bleeding. An angiosarcoma was observed developing from the right pulmonary artery with contiguous spread down smaller artery branches with invasion of the pulmonary parenchyma. Although typical angiosarcomatous areas were observed, the neoplasm was dominated by cells with an epithelioid morphology. Immunohistochemically, the majority of cells stained for endothelial markers factor VIII-related antigen and CD34, but in addition, the cells with an epithelioid morphology stained intensely for cytokeratin. Knowledge of cytokeratin positivity in epithelioid vascular neoplasms is critical to avoid a misdiagnosis of carcinoma, particularly at sites where carcinoma is a much more likely diagnosis.

Cytokeratin subsets can reliably distinguish Barrett's esophagus from intestinal metaplasia of the stomach.

The histological distinction between intestinal metaplasia involving the distal esophagus (Barrett's esophagus [BE]) and intestinal metaplasia of the stomach has important clinical implications and can be difficult even with the use of histochemical mucin stains. Cytokeratin (CK) 7 and 20 are cytoplasmic structural proteins that show restricted expression in normal and malignant epithelia of the gastrointestinal tract. The aim of this study was to determine the use of CK7 and 20 expression in the histological distinction of BE from gastric intestinal metaplasia. CK7 and 20 immunostaining was performed on randomly selected surgical resection (n = 31) and biopsy specimens (n = 34) from patients with long-segment BE and gastric resection specimens (n = 11) and gastric cardia biopsy specimens (n = 13) in patients with histological evidence of intestinal metaplasia. A unique pattern of immunoreactivity designated the Barrett's CK7/20 pattern showed superficial CK20 staining and strong CK7 staining of both superficial and deep glands in 29 of 31 (94%) esophageal resection specimens and 34 of 34 (100%) esophageal biopsy specimens form patients with long-segment BE. A Barrett's CK7/20 pattern was not observed in gastric cardia biopsy specimens (n = 13) or gastric resection specimens (n = 11) in patients with histological evidence of intestinal metaplasia. The sensitivity, specificity, and positive predictive value of a Barrett's CK7/20 pattern for a diagnosis of long-segment BE was 97%, 100%, and 100%, respectively. CK7 and 20 reactivity patterns can reliably identify the location of intestinal metaplasia in the esophagus and stomach using histological material from both routine endoscopic biopsy and surgical resection specimens.

Utility of frozen-section evaluation of lymph nodes in the staging of bronchogenic carcinoma at mediastinoscopy and thoracotomy.

We conducted a retrospective analysis of the utility of frozen-section diagnoses in determining lymph node status at mediastinoscopy in 122 consecutive patients with bronchogenic carcinoma. Thirty-five of 122 patients had one or more lymph nodes with frozen-section evaluation positive for metastatic carcinoma. Subsequent nodal sections not in the original frozen-section study revealed metastatic carcinoma in two additional patients. The false-negative rate was 1.6%. Sensitivity was 94.6%. Predictive value of negative frozen-section evaluation results was 97.7%. Because there were no false-positive frozen-section results, specificity and predictive value for positive results of frozen-section evaluation were 100%. The statuses of individual lymph nodes from these 122 patients were also evaluated. Six hundred twenty lymph nodes were sampled from the mediastinum at mediastinoscopy. Frozen-sections in 47 lymph nodes were positive. Subsequent nodal sections not in the original frozen-sections examination revealed metastatic carcinoma in four additional lymph nodes. The false-negative rate was 0.6%. Sensitivity was 92.2%. Predictive value of negative results from frozen-section evaluation was 99.3%. Because there were no false-positive frozen-section results, specificity and predictive value for positive results of frozen-section examination were 100%. We conclude that frozen-section evaluation of lymph nodes at mediastinoscopy reliably indicates lymph node status, thus enabling the physician to decide whether to proceed to thoracotomy. Thus staging of the carcinoma and definitive surgery can be accomplished during a single anesthetic procedure. Combining mediastinoscopy and thoracotomy with frozen-section diagnostic control also reduces both the length and cost of hospitalization.