Pleuroparenchymal fibroelastosis (PPFE) treated with lung transplantation and review of the literature.

A 26-year-old woman presented with a 15-year history of non-progressive dyspnoea. Chest imaging showed bilateral apical pleural and parenchymal scarring, pleural thickening and bronchiectasis. Pulmonary function tests showed a moderate restrictive defect. Non-invasive workup was non-revealing; therefore, the patient was referred for video-assisted thoracic surgery and lung biopsy. Histopathology revealed pleural thickening and, subpleural parenchymal fibrosis and elastic tissue deposition. Lung parenchyma further away from the pleura was well preserved. Based on these findings, the patient was diagnosed with pleuroparenchymal fibroelastosis (PPFE). Since PPFE is a progressive disorder without effective medical therapies, and given our patient's worsening symptoms, she underwent bilateral lung transplantation. It has been almost 4 years since the lung transplantation, our patient continues to do well. To the best of our knowledge, to date, this is the longest follow-up reported for a PPFE patient undergoing lung transplantation.

Dickkopf-1 (DKK1) promotes tumor growth via Akt-phosphorylation and independently of Wnt-axis in Barrett's associated esophageal adenocarcinoma.

Esophageal adenocarcinoma (EAC) is still associated with poor prognosis, despite modern multi-modal therapies. New molecular markers, which control cell cycle and promote lymph node metastases or tumor growth, may introduce novel target therapies. Dickkopf-1 (DKK1) is a secreted glycoprotein that blocks the oncogenic Wnt/ß-catenin signaling and its aberrant expression has been observed in many malignancies, including EAC. In this study, we investigated the biological role of DKK1 in EAC. Analysis of DKK1 and active ß-catenin expression in human esophageal tissues confirmed a simultaneous DKK1-overexpression together with aberrant activation of ß-catenin signaling in EAC in comparison with Barrett's and healthy mucosa. To elucidate the molecular role of DKK1, the OE33 adenocarcinoma cells, which were found to overexpress DKK1, were subjected to functional and molecular assays following siRNA-mediated DKK1-knockdown. At the functional level, OE33 cell viability, proliferation, migration and invasion were significantly attenuated by the absence of DKK1. At the molecular level, neither DKK1-knockdown nor application of exogenous recombinant DKK1 were found to alter the baseline ß-catenin signaling in OE33 cells. However, DKK1-knockdown significantly abrogated downstream Akt-phosphorylation. On the other hand, the Wnt-agonist, Wnt3a, restored the Akt-phorphorylation in the absence of DKK1, without, however, being able to further stimulate ß-catenin transcription. These findings suggest that the ß-catenin transcriptional activity in EAC is independent of Wnt3a/DKK1 site-of-action and define an oncogenic function for DKK1 in this type of malignancy via distinct activation of Akt-mediated intracellular pathways and independently of Wnt-axis inhibition. Taken together, DKK1 may present a novel therapeutic target in EAC.

Atrial fibrillation after transhiatal esophagectomy with transcervical endoscopic esophageal mobilization: one institution's experience.

BACKGROUND: There have been numerous studies regarding atrial fibrillation (AF) associated with cardiac and pulmonary surgery; however, studies looking at esophagectomy and atrial fibrillation are sparse. The goal of this study was to review our institution's atrial fibrillation rate following esophagectomy in order to better define the incidence and predisposing factors in this patient population. METHODS: A retrospective chart review of all patients undergoing esophagectomy with transcervical endoscopic mobilization of the esophagus (TEEM) at the Medical College of Wisconsin and Affiliated Hospitals from July 2009 through December 2012. RESULTS: Seventy-one patients underwent TEEM esophagectomy during the study period. Of those, 23 (32.4%) patients developed new atrial fibrillation postoperatively. ICU (Intensive Care Unit) length of stay was 7.1 days for those that did not receive amiodarone, compared to 5.3 days for those that did receive amiodarone (p < 0.025). Those that went into AF spent on average 9.3 days in the ICU compared to 4.7 days for their counterparts that did not go into AF (p < 0.006). Total length of stay was not statistically different between populations [15.1 +/- 11.3 days compared to 13.5 +/- 9.4 days for those who did not go into AF (p < 0.281)]. Receiving preoperative amiodarone was found to reduce the overall incidence of AF. There was a trend towards decreased risk of going into AF in those who received preoperative amiodarone with an adjusted hazard ratio of 0.555 (p = 0.057). CONCLUSION: Similar to data reported in previous literature, postoperative atrial fibrillation was found to increase ICU length of stay as well as overall length of hospital stay. Preoperative amiodarone administration displayed a trend toward decreasing the rates of atrial fibrillation in patients undergoing TEEM.

Self-Expanding Metal Stents Improve Swallowing and Maintain Nutrition During Neoadjuvant Therapy for Esophageal Cancer.

BACKGROUND: Patients with locally advanced esophageal cancer can have significant dysphagia. Nutritional support during neoadjuvant therapy is often delivered via nasoenteric or percutaneous feeding tubes. These approaches do not allow for per-oral feeding. AIMS: Evaluate the safety and efficacy of fully covered self-expanding metal esophageal stents for nutritional support during neoadjuvant therapy. METHODS: This was a pilot, prospective study at a single tertiary center. From March 2012 to May 2013, consecutive patients with esophageal cancer eligible for neoadjuvant therapy were enrolled. Metal stents were placed prior to starting neoadjuvant therapy. Data were collected at baseline and predetermined intervals until an endpoint (surgery or disease progression). Outcomes included dysphagia grade, satisfaction of swallowing score, nutritional status (weight, serum albumin), impact on surgery, and adverse events. RESULTS: Fourteen stents were placed in 12 patients (59.1 ± 9.5 years, 11 men, 1 woman). Dysphagia grade (pre 3.4 ± 0.5 vs post 0.2 ± 0.4, p < 0.0001) and swallowing scores (20.2 ± 5.9 vs 6.3 ± 4.7, p < 0.0001) significantly improved after stent placement. Improvements were sustained throughout neoadjuvant therapy. Body weight and serum albumin levels remained stable. Adverse events included severe chest pain (2), food impaction (1), and delayed stent migration (2). Five patients underwent surgical resection. No significant chemoradiation or operative adverse events occurred due to the presence of a stent. CONCLUSIONS: During neoadjuvant therapy for esophageal cancer, self-expanding metal stents are safe and effective in relieving dysphagia and maintaining nutrition. They allow patients to eat orally, thereby improving patient satisfaction. The presence of an in situ stent did not interfere with surgery.

Intrathoracic rosai-dorfman disease: hemorrhage with routine diagnostic procedure.

We present a case of a 33-year-old female with a slow growing, right peribronchial vascular mass and associated symptoms of progressive cough, dyspnea on exertion, and hemoptysis. On routine diagnostic flexible bronchoscopy with needle biopsy, the lesion hemorrhaged extensively requiring emergent thoracotomy, right lower and middle bilobectomy. The histopathology of the specimen was consistent with the rare and unusually located entity Rosai-Dorfman disease.

Intramucosal distribution of WNT signaling components in human esophagus.

BACKGROUND: The molecular mechanisms governing the biology and pathobiology of esophageal squamous mucosa in health and disease are not completely understood. Earlier genome-wide expression study of normal-looking esophageal squamous mucosa has shown differential expression of the Wingless-type MMTV integration site family (Wnt) modulators Dickkopf (Dkk) homologs among healthy individuals and patients with reflux esophagitis and Barrett metaplasia suggesting that the Wnt pathway may be involved in esophageal mucosal biology. STUDY: Seven full-thickness human donor esophagi were cryosectioned for immunohistochemical analysis, and lamina propria (LP), basal (BC), intermediate (IC), and superficial (SC) cells were also dissected by laser-capture microdissection for real-time polymerase chain reaction. RESULTS: Wnt1, 2b, and 3a were expressed primarily in BC, Wnt3, and 5b in LP, and Wnt5a in IC. Frizzled 1, low-density lipoprotein receptor-related protein 6, secreted frizzled-related protein 1, T-cell-specific transcription factor 3, and dishevelled 3 were expressed highest in LP decreasing precipitously medially toward SC. Dkk1 predominantly expressed in SC was more than 100-folds greater than other layers (P<0.001). Dkk4 was expressed primarily in SC but Dkk3 was opposite with greatest expression in LP. Immunohistochemical analysis showed Wnt1 and 3a in BC, Wnt5a in IC and SC, Dkk1 predominantly in SC, Dkk4 in SC and IC, and Dkk3 and SFRP1 in LP and BC

Diverse histologic appearances in pulmonary mucinous cystic neoplasia: a case report.

INTRODUCTION: Primary pulmonary mucinous cystic neoplasia comprises a group of tumors, from benign cystadenoma to mucinous cystadenocarcinoma. CASE PRESENTATION: We report a case of primary pulmonary mucinous cystadenocarcinoma in a 75-year-old woman who was found to have a right hilar mass on a routine chest X-ray. A lobectomy was performed and the resection specimen revealed a multicystic mucinous tumor. Microscopically, the tumor was composed of confluent mucin-filled cystic spaces lined by columnar mucin-secreting cells which ranged from cytologically bland to moderately atypical with 'bronchioloalveolar pattern' invasion into the adjacent parenchyma. Immunohistochemically, tumor cells were positive diffusely for Cytokeratin 7, and focally for Cytokeratin 20 and Thyroid Transcription Factor-1. CONCLUSION: This case highlights the continuous spectrum of pulmonary mucinous cystic neoplasia from benign mucinous cystadenoma to malignant mucinous cystadenocarcinoma, and the probable existence of a 'borderline' mucinous cystic tumor. Although molecular data are lacking to substantiate progression from benign to malignant in these neoplasms, the importance of recognizing the morphologic continuum lies in alerting pathologists to thoroughly examine specimens to rule out invasive foci in tumors with 'borderline' morphology.

Dickkopf homologs in squamous mucosa of esophagitis patients are overexpressed compared with Barrett's patients and healthy controls.

OBJECTIVES: Esophageal mucosal response to acid exposure varies from minimal changes to erosions/ulcerations and Barrett's metaplasia. While differences in acid contact time have been suggested, the reason for these different responses is not completely understood. The aim of this study was to identify and compare gene expression differences between normal distal and proximal squamous esophageal mucosa (SM) in esophagitis patients with that of healthy controls and Barrett's patients. METHODS: Gene microarray was performed on laser-capture microdissected epithelial cells isolated from biopsy specimens followed by real-time PCR. The effect of acidic pH (pH 4.5) on Dickkopf Homolog 1 (Dkk-1) expression in the human esophageal epithelial cell line (Het-1A) was determined. RESULTS: Gene microarray analysis demonstrated that the upregulation of five genes in the distal compared with the proximal SM in esophagitis patients was greater than the healthy controls and Barrett's patients. Overexpression of Dkk-1 and Dkk-4 was further confirmed by real-time PCR. Dkk-1 and Dkk-4 mRNA levels in the distal SM of the esophagitis patients were 7.0- and 3.1-fold higher, respectively, than in the distal SM of the Barrett's patients and 4.1- and 4.1-fold higher than in healthy controls, respectively. Dkk-1 protein expression in the distal esophagitis SM was also higher than the Barrett's patients and healthy controls. Acidic pH exposure of Het-1A cells resulted in Dkk-1 upregulation at the level of both mRNA and protein. CONCLUSIONS: Dkk-1 and Dkk-4 may potentially be involved in the development of different injuries in response to pathological gastroesophageal acid reflux.

Roux-en-Y diversion for debilitating reflux after esophagectomy.

Two patients with debilitating reflux after esophagectomy are reported. Complete relief of symptoms after creation of a Roux-en-Y limb to the gastric conduit is described.

Phase III intergroup study of talc poudrage vs talc slurry sclerosis for malignant pleural effusion.

STUDY OBJECTIVE: To demonstrate the efficacy, safety, and appropriate mode of instillation of talc for sclerosis in treatment of malignant pleural effusions (MPEs). DESIGN: A prospective, randomized trial was designed to compare thoracoscopy with talc insufflation (TTI) to thoracostomy and talc slurry (TS) for patients with documented MPE. MEASUREMENTS: The primary end point was 30-day freedom from radiographic MPE recurrence among surviving patients whose lungs initially re-expanded > 90%. Morbidity, mortality, and quality of life were also assessed. RESULTS: Of 501 patients registered, those eligible were randomized to TTI (n = 242) or TS (n = 240). Patient demographics and primary malignancies were similar between study arms. Overall, there was no difference between study arms in the percentage of patients with successful 30-day outcomes (TTI, 78%; TS, 71%). However, the subgroup of patients with primary lung or breast cancer had higher success with TTI than with TS (82% vs 67%). Common morbidity included fever, dyspnea, and pain. Treatment-related mortality occurred in nine TTI patients and seven TS patients. Respiratory complications were more common following TTI than TS (14% vs 6%). Respiratory failure was observed in 4% of TS patients and 8% of TTI patients, accounting for five toxic deaths and six toxic deaths, respectively. Quality-of-life measurement demonstrated less fatigue with TTI than TS. Patient ratings of comfort and safety were also higher for TTI, but there were no differences on perceived value or convenience of the procedures. CONCLUSIONS: Both methods of talc delivery are similar in efficacy; TTI may be better for patients with either a lung or breast primary. The etiology and incidence of respiratory complications from talc need further exploration.

A decade of experience with transthoracic and transhiatal esophagectomy.

BACKGROUND: Morbidity and mortality remain significant for transthoracic (TT) and transhiatal (TH) esophagectomy. We report a case-specific approach employing either resection to minimize perioperative morbidity and mortality. METHODS: All primary esophageal resections performed for benign and malignant esophageal disease were reviewed over a 10-year period. The operative approach was tailored to the location and extent of disease and the physiologic reserve of the patient. RESULTS: In all, 115 patients underwent esophagectomy for benign (25) and malignant (90) disease. Fifty-six TT and 59 TH resections were performed. Four emergent TT cases did not have reconstruction. There was 1 hospital mortality. Perioperative transfusion was avoided in 65 patients. Respiratory complications occurred in 15. Three patients had a cervical anastomotic leak requiring open wound drainage. No association between resection type and complication was evident. CONCLUSIONS: The judicious use of both TT and TH esophagectomy resulted in an operative mortality of less than 1%, reduced operative blood loss, and a relatively low rate of perioperative complications.