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.

Cellular and Kaposi's sarcoma-associated herpes virus microRNAs in sepsis and surgical trauma.

Once a patient is in septic shock, survival rates drop by 7.6% for every hour of delay in antibiotic therapy. Biomarkers based on the molecular mechanism of sepsis are important for timely diagnosis and triage. Here, we study the potential roles of a panel of cellular and viral miRNAs as sepsis biomarkers. We performed genome-wide microRNA (miRNA) expression profiling in leukocytes from septic patients and nonseptic controls, combined with quantitative RT-PCR in plasmas from two cohorts of septic patients, two cohorts of nonseptic surgical patients and healthy volunteers. Enzyme-linked immunosorbent assay, miRNA transfection and chromatin immunoprecipitation were used to study the effects of Kaposi sarcoma herpes virus (KSHV) miRNAs on interleukin's secretion. Differences related to sepsis etiology were noted for plasma levels of 10 cellular and 2 KSHV miRNAs (miR-K-10b and miR-K-12-12*) between septic and nonseptic patients. All the sepsis groups had high KSHV miRNAs levels compared with controls; Afro-American patients had higher levels of KSHV-miR-K12-12* than non-Afro-American patients. Both KSHV miRNAs were increased on postoperative day 1, but returned to baseline on day 7; they acted as direct agonists of Toll-like receptor 8 (TLR8), which might explain the increased secretion of the IL-6 and IL-10. Cellular and KSHV miRNAs are differentially expressed in sepsis and early postsurgical patients and may be exploited for diagnostic and therapeutic purposes. Increased miR-K-10b and miR-K12-12* are functionally involved in sepsis as agonists of TLR8, forming a positive feedback that may lead to cytokine dysregulation.

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.

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.

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.

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.

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.

Assessment of a pathophysiology-directed treatment for symptomatic epiphrenic diverticulum.

Epiphrenic diverticulum is a rare disease associated with distal esophageal obstruction and a weakened muscularis propria. We have adhered to an operative strategy of excision (diverticulectomy), repair of esophageal wall, and relief of functional and mechanical obstruction. We sought to assess this pathophysiology-directed treatment strategy. From 1987 to 2005, 44 patients underwent surgery for epiphrenic diverticulum. Diverticulectomy, repair, and relief of distal obstruction was performed in 35 (80%) and esophagectomy in nine (10%). Outcome (symptoms, diet, subsequent therapies and morbidity) was assessed by follow-up. Forty of 44 patients had preoperatively identifiable esophageal obstruction (91%). Distal obstruction was functional in 32 patients and mechanical in 24; these conditions coexisted in 16. After surgery, there were no in-hospital deaths; 15 patients experienced 22 in-hospital complications. Survival was 90% at 5 years and 72% at 10 years. Symptoms improved in most patients (P = 0.0004), except for gastroesophageal reflux; new symptoms of gastroesophageal reflux occurred in 9/27 (33%) without this symptom preoperatively. Diet was less restricted postoperatively (P < 0.0001). Of 35 patients undergoing diverticulectomy, three (8.6%) required dilatation and two (6%) reoperation; 6/9 esophagectomy patients required dilatations. Preoperative assessment must include evaluation for mechanical obstruction. Adherence to a pathophysiology-directed operative strategy is safe and will improve the symptoms of most patients, with little need for reintervention. However, occasional patients will experience new symptoms, particularly reflux. Esophagectomy is the alternative for patients who are not candidates for diverticulectomy, repair of esophageal wall, and relief of distal obstruction.

Can extent of high grade dysplasia in Barrett's oesophagus predict the presence of adenocarcinoma at oesophagectomy?

BACKGROUND: Optimal management of Barrett's oesophagus complicated by high grade dysplasia is controversial. Recently, the extent of high grade dysplasia was described as a predictor of subsequent development of cancer in patients undergoing continued surveillance. However, there is no universal agreement on the definition of extent of high grade dysplasia. AIM: To determine if extent of high grade dysplasia in Barrett's oesophagus is a predictor of the presence of adenocarcinoma at the time of oesophagectomy. METHODS: Forty two patients with Barrett's oesophagus and high grade dysplasia who underwent oesophagectomy between 1985 and 1999 were identified from a prospective database. All pathological specimens, including preoperative endoscopic biopsies and post-oesophagectomy sections, were reviewed in a blinded fashion by one expert gastrointestinal pathologist to determine the extent of high grade dysplasia. The extent of high grade dysplasia was defined using two different criteria, one from the Cleveland Clinic and one from the Mayo Clinic. RESULTS: Twenty four of 42 patients (57%) had unsuspected cancer at the time of oesophagectomy. Using the Cleveland Clinic definition, 10 of 21 (48%) patients with focal high grade dysplasia had carcinoma compared with 14 of 21 patients (67%) with diffuse high grade dysplasia (p=0.35). Using the Mayo Clinic definition, adenocarcinoma was found in five of seven (72%) patients with focal high grade dysplasia compared with 19 of 35 (54%) with diffuse high grade dysplasia (p=0.68). CONCLUSIONS: The extent of high grade dysplasia, regardless of how it is defined, does not predict the presence of unsuspected adenocarcinoma at oesophagectomy. There is no evidence as yet that the extent of high grade dysplasia can be used as a basis for decision making in these patients.

Observer variation in the diagnosis of superficial oesophageal adenocarcinoma.

BACKGROUND AND AIMS: When to perform oesophagectomy for neoplastic progression in Barrett's oesophagus is controversial. Some resect for high grade dysplasia whereas others defer treatment until intramucosal adenocarcinoma is diagnosed. Interobserver agreement for a diagnosis of high grade dysplasia or intramucosal adenocarcinoma remains unknown and may have therapeutic implications. METHODS: Histological slides from 75 oesophagectomy specimens with high grade dysplasia or T(1) adenocarcinoma were blindly reviewed by two gastrointestinal pathologists and one general surgical pathologist, and classified as high grade dysplasia, intramucosal adenocarcinoma, or submucosal adenocarcinoma. A subsequent re-review of all 75 cases by the same observers following establishment of uniform histological criteria was undertaken. Interobserver agreement was determined by kappa statistics. Coefficients <0.21, 0.21-0.40, 0.41-0.60, 0.61-0.80, and >0.80 were considered poor, fair, moderate, good, and very good agreement, respectively. RESULTS: Interobserver agreement among all pathologists and between gastrointestinal pathologists when comparing high grade dysplasia with intramucosal adenocarcinoma was only fair (k=0.42; 0.56, respectively) and did not substantially improve on subsequent re-evaluation following establishment of uniform histological criteria (K=0.50; 0.61, respectively). CONCLUSIONS: When evaluating resection specimens and after implementation of uniform histological criteria, even experienced gastrointestinal pathologists frequently disagree on a diagnosis of high grade dysplasia versus intramucosal adenocarcinoma. Treatment strategies based on the histological distinction of high grade dysplasia from intramucosal adenocarcinoma using limited biopsy specimens should be re-evaluated.

The solitary pulmonary nodule: a primer on differential diagnosis.

Despite significant advances in noninvasive imaging techniques, management of the solitary pulmonary nodule (SPN) remains a challenge for chest physicians. Patients with SPNs are frequently asymptomatic, and the physical examination is seldom revealing. Accurate diagnosis is essential, because >50% of patients will require prompt disease-specific therapy. The complexity of the problem is best appreciated by reviewing the differential list, which includes nearly 80 distinct clinical entities. Consequently, a thorough understanding of the more common etiologies is necessary to adequately treat patients with SPNs.