Background

Chylothorax is a rare but potentially lethal complication of esophagectomy. The study aims were to evaluate the rate of postesophagectomy chylothorax, identify associated risk factors and compare postoperative outcomes with patients who do not develop chylothorax.

Methods

We reviewed 892 consecutive patients undergoing esophagectomy (1997-2008). Preoperative, operative and postoperative details, including adverse outcomes and mortality, were analyzed.

Results

We identified postesophagectomy chylothorax in 34 patients (3.8%). Chylothorax was significantly associated with adverse outcomes, including 30-day major complications (85% vs. 46%; p<0.001) and mortality (17.7 vs. 3.9%, p<0.001). Patients with chylothorax were significantly more likely to develop sepsis (p=0.001), pneumonia (p=0.009), need reintubation (p=0.002) or require reoperation (p<0.001). Median length of stay was significantly longer (17 vs. 8 days; p=0.005). Median time to chylothorax diagnosis was 5 days. Thoracic duct ligation was performed in 62% (n=21; median 13 days after esophagectomy). Repeat duct ligation for persistent chylothorax was required in 2 patients. Squamous cell cancer histology (9/34; 26%) was an independent predictor of postoperative chylothorax (OR 4.18; 95% CI 1.39, 12.6). Odds of chylothorax were 36 times greater with average daily chest tube output >400 ml in the first 6 postoperative days (OR 35.9; 95% CI 8.2, 157.8).

Conclusions

Postoperative chylothorax is associated with significant postoperative morbidity and mortality. Patients with squamous cell cancer may be at increased risk. In addition, >400 ml average daily chest tube output in the early postoperative period should prompt fluid analysis for chylothorax to facilitate early diagnosis and consideration of thoracic duct ligation.

Background

High expression of Bmi-1, a key regulatory component of the polycomb repressive complex-1, has been associated with many solid and hematologic malignancies including esophageal squamous cell carcinoma. However, little is known about the role of Bmi-1 in esophageal adenocarcinoma. The aim of this study is to investigate the amplification and high expression of Bmi-1 and the associated clinicopathologic characteristics in esophageal adenocarcinoma and squamous cell carcinoma.

Methods

The protein expression level of Bmi-1 was detected by immunohistochemistry (IHC) from tissue microarrays (TMA) constructed at the University of Rochester from using tissues accrued between 1997 and 2005. Types of tissues included adenocarcinoma, squamous cell carcinoma and precancerous lesions. Patients’ survival data, demographics, histologic diagnoses and tumor staging data were collected. The intensity (0–3) and percentage of Bmi-1 expression on TMA slides were scored by two pathologists. Genomic DNA from 116 esophageal adenocarcinoma was analyzed for copy number aberrations using Affymetrix SNP 6.0 arrays. Fisher exact tests and Kaplan-Meier methods were used to analyze data.

Results

By IHC, Bmi-1 was focally expressed in the basal layers of almost all esophageal squamous mucosa, which was similar to previous reports in other organs related to stem cells. High Bmi-1 expression significantly increased from squamous epithelium (7%), columnar cell metaplasia (22%), Barrett’s esophagus (22%), to low- (45%) and high-grade dysplasia (43%) and adenocarcinoma (37%). The expression level of Bmi-1 was significantly associated with esophageal adenocarcinoma differentiation. In esophageal adenocarcinoma, Bmi-1 amplification was detected by DNA microarray in a low percentage (3%). However, high Bmi-1 expression did not show an association with overall survival in both esophageal adenocarcinoma and squamous cell carcinoma.

Conclusions

This study demonstrates that high expression Bmi-1 is associated with esophageal adenocarcinoma and precancerous lesions, which implies that Bmi-1 plays an important role in early carcinogenesis in esophageal adenocarcinoma.

Background

Esophageal cancer consists of two major histologic types: esophageal squamous cell carcinoma (ESCC) predominant globally and esophageal adenocarcinoma (EAC) with a higher incidence in westernized countries. Five-year overall survival is 15%. Clinical trials frequently combine histologies although they are different diseases with distinct origins. In the evolving era of personalized medicine and targeted therapies, we hypothesized that ESCC and EAC have genomic differences important for developing new therapeutic strategies for esophageal cancer.

Methods

We explored DNA copy number abnormalities (CNAs) in 70 ESCCs with publicly available array data and 189 EAC from our group. All data was from Affymetrix single nucleotide polymorphism (SNP) arrays. Analysis was performed with Nexus 5.0 Copy number software using a SNPRank segmentation algorithm. Log ratio thresholds for copy number gain and loss were set at +/− 0.2 (approximately 2.3 and 1.7 copies respectively).

Results

ESCC and EAC genomes showed some CNAs with similar frequencies (e.g., CDKN2A, EGFR, KRAS, MYC, CDK6, MET) but also many CNAs with different frequencies between histologies, most of which were amplification events. Some of these regions harbor genes to which targeted therapies are currently available (VEGFA, ERBB2) or where agents are in clinical trials (PIK3CA, FGFR1). Other regions contain putative oncogenes that may be targeted in the future.

Conclusions

Using SNP arrays we compared genomic abnormalities in a large cohort of EAC and ESCC. We report here the similar and different frequencies of CNAs in ESCC and EAC. These results may allow development of histology-specific therapeutic agents for esophageal cancer.

Background

The incidence of esophageal adenocarcinoma is rapidly increasing and is now one of the leading causes of cancer death in the western world. MicroRNAs (miRNAs) are small non-coding RNAs which regulate the expression of protein-encoding genes and are involved in the development, progression and prognosis of other malignancies. We hypothesized that global miRNA expression would predict survival and lymph node involvement in a cohort of surgically resected esophagus cancer patients.

Methods

miRNA analysis was performed using a custom Affymetrix microarray with probes for 462 known human, 2102 predicted human, 357 mouse and 238 rat miRNAs. miRNA expression was evaluated in 45 primary tumors, and the association of miRNA expression with patient survival and lymph node metastasis was assessed. The prognostic impact of identified unique miRNAs was verified with quantitative RT-PCR.

Results

Our data indicate that the expression of individual human miRNA species is significantly associated with post-resection patient survival. Using data from five unique miRNAs, we were further able to generate a combined miRNA expression signature that is associated with patient survival (p=0.005; HR = 3.6) independent of node involvement and overall stage. The expression of three miRNAs (miR-99b, miR-199a_3p and _5p) was also associated with the presence of lymph node metastasis.

Conclusions

These results suggest miRNA expression profiling could provide prognostic utility in staging esophagus cancer patients and treatment planning with endoscopic and neoadjuvant therapies. The alterations of specific miRNAs may further elucidate steps in the metastatic pathway and allow for development of targeted therapy.

Purpose

Chromosomal gain at 7q21 is a frequent event in esophageal adenocarcinoma (EAC). However, this event has not been mapped with fine resolution in a large EAC cohort and its association with clinical endpoints and functional relevance are unclear.

Experimental design

We used a cohort of 116 patients to fine map the 7q21 amplification using SNP microarrays. Prognostic significance and functional role of 7q21 amplification and its gene expression were explored.

Results

Amplification of the 7q21 region was observed in 35% of tumors with a focal, minimal amplicon containing 6 genes. 7q21 amplification was associated with poor survival and analysis of gene expression identified CDK6 as the only gene in the minimal amplicon whose expression was also associated with poor survival. A low level amplification (10%) was observed at the 12q13 region containing the CDK6 homolog, CDK4. Both amplification and expression of CDK4 correlated with poor survival. A combined model of both CDK6 and CDK4 expression is a superior predictor of survival than either alone. Specific knockdown of CDK4 and/or CDK6 by siRNAs shows that they are required for proliferation of EAC cells and that their function is additive. PD-0332991 targets the kinase activity of both molecules and suppresses proliferation and anchorage-independence of EAC cells through activation of the pRB pathway.

Conclusions

We suggest that CDK6 is the driver of 7q21 amplification and that both CDK4 and CDK6 are prognostic markers and bona fide oncogenes in EAC. Targeting these molecules may constitute a viable new therapy for this disease.

Background

Surgical resection is the standard of care for patients with resectable non-small cell lung cancer or selected patients with pulmonary metastases. However, for high-risk patients radiofrequency ablation (RFA) may offer an alternative option. The objective of this study was to evaluate computed tomography guided (CT-guided) RFA for high-risk patients and report our initial experience in 100 consecutive patients by a thoracic surgical service.

Methods

Medically inoperable patients were offered RFA. Thoracic surgeons evaluated and performed RFA under CT guidance. Patients were followed in the thoracic surgery clinic. The primary endpoint evaluated was overall survival.

Results

One hundred patients underwent image-guided RFA for lung neoplasm (40 men, 60 women; median age 73.5 years; range 26-95). Forty-six (46%) patients with primary lung neoplasm, 25 (25%) with recurrent cancer and 29 (29%) with pulmonary metastases underwent RFA. The mean follow-up for alive patients was 17 months. The median overall survival for entire group of patients was 23 months. The probabilities of 2-year survival for the entire group, primary lung cancer patients, recurrent cancer patients and metastatic cancer patients were 49 % (CI 37- 60), 50 %(CI 33-65), 55% (CI 25- 77) and 41% (CI 19-62), respectively.

Conclusion

Our experience indicates that image-guided RFA done by the thoracic surgeons is feasible and safe in high-risk patients with lung neoplasm with reasonable results in patients who are not fit for surgery. Thoracic surgeons can perform RFA safely, and should continue to investigate this new image-guided modality which may offer an alternative option in medically inoperable patients.

Objectives

Surgical resection is the preferred treatment in selected patients with pulmonary metastases. In high-risk patients, radiofrequency ablation (RFA) may offer an alternative option. RFA may be used either alone or in combination with surgical resection as a lung parenchymal-sparing approach. Our objectives were to evaluate the intermediate term outcomes after RFA and to determine the prognostic variables associated with outcome in patients with pulmonary metastases

Methods

Thoracic surgeons evaluated and performed RFA under computed-tomography (CT) guidance or in combination with surgical resection as a lung parenchymal-sparing modality. Patients were monitored in the thoracic surgery clinic for recurrence and survival.

Results

Twenty-two patients {10 men, 12 women; median age 63 years (37-88)} underwent RFA. The primary cancer was colorectal in 9 (41%), renal in 2 (9%), sarcoma in 4 (18%) and other in 7 (32%) patients. CT-guided RFA was performed as a sole modality of treatment in 17 patients (77%), and in combination with surgical resection in 5 (23%) patients. There were no procedure-related mortalities. At a mean follow-up of 27 months (13.3-53.6 months), 9 patients are alive. The median survival was 29 months (CI 9.1-33.8). Size of the lesion was an important prognostic variable associated with overall and disease-free survival (P<0.05).

Conclusions

Our experience indicates that RFA is safe in this group of pulmonary metastases patients with reasonable results. Surgery remains the standard for resectable patients, but RFA offers an alternative option in selected patients or may be used as a parenchymal-sparing approach in combination with surgical resection in selected patients.

Abstract

Manganese superoxide dismutase (MnSOD) is a genetically engineered therapeutic DNA/liposome containing the human MnSOD transgene. Preclinical studies in mouse models have demonstrated that the expression of the human MnSOD transgene confers protection of normal tissues from ionizing irradiation damage. This is a phase I study of MnSOD plasmid liposome (PL) in combination with standard chemoradiation in surgically unresectable stage III non-small-cell lung cancer. Chemotherapy (carboplatin and paclitaxel) was given weekly (for 7 weeks), concurrently with radiation. MnSOD PL was swallowed twice a week (total 14 doses), at three dose levels: 0.3, 3, and 30 mg. Dose escalation followed a standard phase I design. Esophagoscopy was done at baseline, day 4, and 6 weeks after radiation with biopsies of the squamous lining cells. DNA was extracted and analyzed by PCR for the detection of the MnSOD transgene DNA. Ten patients with AJCC stage IIIA (three) and IIIB (seven) completed the course of therapy. Five had squamous histology, two adenocarcinoma, one large cell, and two not specified. Patients were treated in three cohorts at three dose levels of MnSOD PL: 0.3 (three patients), 3 (three patients), and 30 mg (four patients). The median dose of radiation was 77.7 Gy (range 63–79.10 Gy). Overall response rate for the standard chemoradiation regimen was 70% (n = 10). There were no dose-limiting toxicities reported in all three dosing tiers. It is concluded that the oral administration of MnSOD PL is feasible and safe. The phase II recommended dose is 30 mg.

Esophageal toxicity is a side effect of some chemoradiotherapy treatments for lung cancer. Preclinical gene therapy studies have demonstrated that expression of the human manganese peroxide dismutase gene (MnSOD) confers protection of normal tissues from ionizing irradiation damage. Here, Tarhini and colleagues follow up on previous preclinical results and conduct a phase I dose escalation study examining the safety of an ingestible genetically engineered DNA/liposome containing the human MnSOD transgene in research subjects undergoing chemotherapy.

Background

Normal bronchial tissue expression of GRPR, which encodes the gastrin-releasing peptide receptor, has been previously reported by us to be associated with lung cancer risk in 78 subjects, especially in females. We sought to define the contribution of GRPR expression in bronchial epithelia to lung cancer risk in a larger case-control study where adjustments could be made for tobacco exposure and sex.

Methods

We evaluated GRPR mRNA levels in histologically normal bronchial epithelial cells from 224 lung cancer patients and 107 surgical cancer-free controls. Associations with lung cancer were tested using logistic regression models.

Results

Bronchial GRPR expression was significantly associated with lung cancer (OR = 4.76; 95% CI = 2.32-9.77) in a multivariable logistic regression (MLR) model adjusted for age, sex, smoking status and pulmonary function. MLR analysis stratified by smoking status indicated that ORs were higher in never and former smokers (OR = 7.74; 95% CI = 2.96-20.25) compared to active smokers (OR = 1.69; 95% CI = 0.46-6.33). GRPR expression did not differ by subject sex, and lung cancer risk associated with GRPR expression was not modified by sex.

Conclusions

GRPR expression in non-cancerous bronchial epithelium was significantly associated with the presence of lung cancer in never and former smokers. The association in never and former smokers was found in males and females. Association with lung cancer did not differ by sex in any smoking group.

The HER2 oncogene was recently reported to be amplified and overexpressed in esophageal adenocarcinoma. However, the relationship of HER2 amplification in esophageal adenocarcinoma with prognosis has not been well defined. The scoring systems for clinically evaluating HER2 in esophageal adenocarcinoma are not established. The aims of the study were to establish a HER2 scoring system and comprehensively investigate HER2 amplification and overexpression in esophageal adenocarcinoma and its precursor lesion. Using a tissue microarray, containing 116 cases of esophageal adenocarcinoma, 34 cases of BE, 18 cases of low grade dysplasia and 15 cases of high grade dysplasia, HER2 amplification and overexpression were analyzed by HercepTest and CISH methods. The amplification frequency in an independent series of 116 esophageal adenocarcinoma samples was also analyzed using Affymetrix SNP 6.0 microarrays. In our studies, we have found that HER2 amplification does not associate with poor prognosis in total 232 esophageal adenocarcinoma patients by CISH and high density microarrays. We further confirm the similar frequency of HER2 amplification by CISH (18.10%; 21/116) and SNP 6.0 microarrays (16.4%, 19/116) in esophageal adenocarcinoma. HER2 protein overexpression was observed in 12.1 % (14/116) of esophageal adenocarcinoma and 6.67% (1/15) of HGD. No HER2 amplification or overexpression was identified in BE or LGD. All HER2 protein overexpression cases showed HER2 gene amplification. Gene amplification was found to be more frequent by CISH than protein overexpression in esophageal adenocarcinoma (18.10% vs 12.9%). A modified two-step model for esophageal adenocarcinoma HER-2 testing is recommend for clinical esophageal adenocarcinoma HER-2 trial.

OBJECTIVE

Laparoscopic repair of giant paraesophageal hernia (GPEH) is a complex operation requiring significant laparoscopic expertise. Our objective was to compare our current approach and outcomes with LRGPEH to our previous experience.

METHODS

A retrospective review of patients undergoing non-emergent LRGPEH, stratified by early and current era (1/1997–6/2003 and 7/2003–6/2008) was performed. Surgeon credentialing required a minimally invasive surgical fellowship and/or careful proctoring prior to independent LRGPEH. We evaluated clinical outcomes, barium esophagram and quality-of-life (QoL).

RESULTS

LRGPEH was performed in 662 patients (median age 70, range 19–92); median percent of herniated stomach 70% (range 30–100%). Over time, use of Collis gastroplasty decreased (86% to 53%) as did crural mesh reinforcement (17% to 12%). Current era patients were 50% more likely to have a Charlson comorbidity index score >3. Common complications included pleural effusion (56/652; 9%) and pneumonia (29/653; 4%). Thirty-day mortality was 1.7% (11/662). Mortality and complication rates were stable over time, despite increasing comorbid disease in the current patient cohort. Post-operative GERD-health-related QoL scores were available for 489 patients (30-month median follow-up) with “Good” to “Excellent” results in 90% (438/489). Radiographic recurrence (15.7%) was not associated with symptom recurrence. Reoperation occurred in 3.2% (21/662).

CONCLUSIONS

Over time, we have obtained significant minimally invasive experience and refined our approach to LRGPEH. Perioperative morbidity and mortality remain low, despite increased comorbid disease in the current patient cohort. LRGPEH provided excellent patient satisfaction and symptom improvement, even with small radiographic recurrences. Reoperation rates were comparable to the best open series.

Background and Objectives:

Gastroesophageal reflux disease (GERD) is commonly associated with morbid obesity (MO). Antireflux surgery has a higher failure rate in MO and addresses only one of the comorbidities present. This paper reviews the results of laparoscopic Rouxen-Y gastric bypass (LRYGBP) performed for recalcitrant GERD in MO.

Methods:

Patients with recalcitrant GERD and a body mass index (BMI)>35 undergoing LRYGBP were included. LRYGB included crural repair, creation of a small gastric pouch (30 mL), and intestinal bypass (150 to 180 cm). All patients were followed in clinic and by telephone.

Results:

From February 1999 to April 2001, 57 patients (51 F, 6 M) with a mean age of 43 (range, 22 to 67) and a median BMI of 43 underwent LRYGBP. Hiatal hernia or esophagitis, or both, were present in 48, Barrett's in 2. LRYGBP was possible in 52 patients; 5 required open conversion. The median hospital stay was 3 days. Complications included 1 leak, 1 pulmonary emboli, 2 reoperations for internal roux limb hernia, and 7 gastrojejunal strictures. At a mean follow-up of 18 months (range, 3 to 30), all patients report improvement or no symptoms of GERD and a mean weight loss of 40 kg (range, 16 to 70). Quality of life scores (SF-36) were above national norms for physical and mental components (median 55, norms=50). GERD-health related quality of life median score was <1 (scale, 0 to 45, 0=asymptomatic, 45=worse).

Conclusion:

LRYGBP was effective for recalcitrant GERD in MO. LRYGBP also led to weight loss and improvement in other comorbidites. Surgeons with minimally invasive expertise should consider LRYGBP for treatment of GERD in the morbidly obese.

Objectives:

In recent years, older patients are being referred for esophagectomy, and the associated morbidity and mortality is not well defined. Advances in minimally invasive techniques now allow minimally invasive esophagectomy (MIE) to be performed that may minimize the morbidity of this procedure. The objective of this report was to summarize our experience with MIE in the elderly.

Methods:

From February 1997 through February 2001, 41 patients (14 women, 27 men) 75 years of age or older (mean age 78, range 75 to 89) underwent esophagectomy (28 for adenocarcinoma, 7 squamous, 6 Barrett's with high-grade dysplasia).

Results:

Esophagectomy was performed in a minimally invasive fashion in 41 patients. No open conversions were necessary. The median ICU stay was 1 day (range 1 to 34). The median hospital stay was 7 days (range 5 to 50). Major morbidity occurred in 19% of the cases and included 1 persistent air leak, 1 case of pneumonia with acute respiratory failure, 1 tracheal tear, 1 chylothorax, and 1 myocardial infarction. Three anastomotic leaks and 1 small bowel perforation occurred. All were recognized early and treated surgically. No perioperative mortalities took place.

Conclusion:

In our center, MIE was performed in elderly patients with an acceptable morbidity, low mortality, and reduced length of hospital stay compared with that in previous reports.

Objectives

Esophagectomy is the standard treatment for T1 esophageal cancer (EC). With an increasing interest in endoscopic therapies particularly for T1 EC, our objectives were to evaluate the long term outcomes following esophagectomy and to examine the pathological features of T1 cancer in detail to determine the suitability for potential endoscopic therapy.

Methods

We reviewed the outcomes of esophagectomy in 100 consecutive patients with T1 EC. The primary endpoints studied were overall survival (OS) and disease-free survival (DFS). In addition to detailed pathology review, we evaluated prognostic variables associated with survival.

Results

Esophagectomy was performed in 100 patients (79 men, 21 women; median age 68 years) for T1 EC (adenocarcinoma 91, squamous 9; intramucosal (T1a):29, submucosal (T1b):71). The 30 day mortality was 0%. Resection margins were microscopically negative in 99% (99/100) of patients. N1 disease was present in 21 patients (T1a:2/29(7%); T1b:19/71(27%)), associated high-grade dysplasia in 64/100 (64%) and angiolymphatic invasion in 19/100 (19%) of patients. At a median follow-up of 66 months, estimated 5-year OS and 3-year DFS were 62% and 80%, respectively, for all patients (including N1). Nodal status and tumor size were significantly associated with overall survival and disease-free survival, respectively.

Conclusions

Esophagectomy can be performed safely in patients with T1 cancer with good long term results. Many patients with T1 EC have several risk factors which may preclude adequate treatment with endoscopic therapy. Further prospective studies are required to evaluate endoscopic therapies. Esophagectomy should continue to remain the standard treatment in patients with T1 EC.

Background:

Tube thoracostomy remains the standard of care for the treatment of pneumothoraces and simple effusions. This report describes a favorable experience with the 8.3 French pigtail catheter as a less invasive alternative to traditional chest tube insertion.

Methods:

We retrospectively reviewed 109 consecutive pigtail catheter placements. Catheters were inserted under local anesthesia at the bedside without radiographie guidance. Pre- and post-insertion chest radiographs were reviewed to determine efficacy of drainage.

Results:

Fifty-one of 109 patients (47%) were mechanically ventilated and 26 patients (24%) had a coagulopathy. There were no complications related to pigtail catheter insertion. Seventy-seven pigtail catheters were placed for pleural effusion and 32 for pneumothorax. Mean effusion volume decreased from 43 to 9 percent, and drainage averaged 2899 ml over 97 hours. Mean pneumothorax size diminished from 38 to 1 percent during an average 71-hour placement. Clinical success rates in the effusion and pneumothorax groups were 86 and 81 percent, respectively.

Conclusion:

The pigtail catheter offers reliable treatment of pneumothoraces and simple effusions and is a safe and less invasive alternative to tube thoracostomy.

Background and Objectives:

Lymph node metastases are the most important prognostic factor in patients with esophageal cancer. Histologic examination misses micrometastases in up to 20% of lymph nodes evaluated. In addition, non-invasive imaging modalities are not sensitive enough to detect small lymph nodes metastases. The objective of this study was to investigate the use of reverse transcriptase-polymerase chain reaction (RT-PCR) of messenger RNA (mRNA) for carcinoembryonic antigen (CEA) to increase the detection of micrometastases in lymph nodes from patients with esophageal cancer.

Methods:

RT-PCR of CEA mRNA was performed in lymph nodes from patients with malignant and benign esophageal disease. Each specimen was examined histopathologically and by RT-PCR and the results were compared.

Results:

Metastases were present in 29 of 60 (48%) lymph nodes sample by minimally invasive staging from 13 patients with esophageal cancer when examined histopathologically. RT-PCR identified nodal metastases in 46 of these 60 (77%) samples. RT-PCR detected CEA mRNA in all 29 histologically positive samples and in 17 histologically negative lymph nodes. All lymph nodes from patients with benign disease (n=15) were negative both histopathologically and by RT-PCR. The stage of two patients was reclassified based on the RT-PCR results, which identified lymph node spread undetected histopathologically. Both of these patients developed recurrent disease after resection of the primary tumor.

Conclusions:

RT-PCR is more sensitive than histologic examination in the detection of lymph node metastases in esophageal cancer and can lead to diagnosis of a more advanced stage in some patients. The combination of minimally invasive surgical techniques in combination with new molecular diagnostic techniques may improve our ability to stage cancer patients.

Background:

Recent advances in laparoscopic and thoracoscopic surgery have made it possible to perform esophagectomy using minimally invasive techniques. The aim of this report was to present our preliminary experience with minimally invasive esophagectomy.

Methods:

We reviewed our experience on eight patients who underwent minimally invasive esophagectomy using either laparoscopic and/or thoracoscopic techniques from June 1996 to May 1997. Indications for esophagectomy included stage I carcinoma (5), palliative resection (1), Barrett's with high grade dysplasia (1) and end stage achalasia (1).

Results:

The average age was 68 years (54-82). The surgical approach to esophagectomy included laparoscopic transhiatal esophagectomy with cervical anastomosis (n=4), thoracoscopic and laparoscopic esophagectomy with cervical anastomosis (n=1), and laparoscopic mobilization with right mini-thoracotomy and intra-thoracic anastomosis (n=3). Conversion to mini-laparotomy was required in two patients (25%) to complete esophageal dissection and facilitate gastric pull-up. The mean operative time was 460 minutes. The mean intensive care stay was 1.9 days (range of 0-7 days) with a mean hospital stay of 13-8 days. Minor complications included atrial fibrillation (n=1), pleural effusion (n=2) and persistent air leak (n=1). Major complications included cervical anastomotic leak (n=1), and delayed gastric emptying requiring pyloroplasty (n=1). There was no perioperative mortality.

Conclusions:

This preliminary experience suggests that minimally invasive esophagectomy is safe and feasible in centers with experience in advanced minimally invasive surgical procedures. Further studies are necessary to determine advantages over open esophagectomy.

We have previously described the expression of CD44, CD90, CD117 and CD133 in NSCLC tumors, adjacent normal lung, and malignant pleural effusions (MPE). Here we describe the unique subset of tumors expressing CD117 (KIT), a potential therapeutic target. Tumor and adjacent tissue were collected from 58 patients. Six MPE were obtained before therapy. Tissue was paraffin embedded for immunofluorescent microscopy, disaggregated and stained for flow cytometry or cryopreserved for later culture. The effect of imatinib on CD117high/KIT+ tumors was determined on first passage cells; absolute cell counts and flow cytometry were readouts for drug sensitivity of cell subsets. Primary tumors divided into KITneg and KIT+ by immunofluorescence. By more sensitive flow cytometric analysis, CD117+ cytokeratin+ cells were detected in all tissues (1.1% of cytokeratin+ cells in normal lung, 1.29% in KIT “negative” tumors, 40.7% in KIT+ tumors, and 0.4% in MPE). In KIT+/CD117high, but not KIT+/CD117low tumors, CD117 was overexpressed 3.1-fold compared to normal lung. Primary cultures of CD117high tumors were sensitive to imatinib (5 µM) in short term culture. We conclude that NSCLC tumors divide into CD117low and CD117high. Overexpression of CD117 in CD117high NSCLC supports exploring KIT as a therapeutic target in this subset of patients.

Background:

A number of case reports have described the application of minimally invasive surgical techniques to accomplish esophagectomy. However, most reports have employed thoracoscopic or laparoscopic techniques to perform esophagectomy in addition to an “access” incision which often approaches a standard laparotomy or thoracotomy.

Case Report:

This report describes a total laparoscopic transhiatal esophagectomy in a 55 year old female with Barrett's esophagus and high grade dysplasia.

Conclusions:

The patient had an uneventful recovery and was discharged home on the fourth day after a total laparoscopic esophagectomy. This report demonstrates the technical feasibility of this complex procedure by a minimally invasive approach.

Extraosseous osteosarcoma (EOO) is a malignant mesenchymal neoplasm that is located in the soft tissues without direct attachment to the skeletal system and that produces osteoid, bone, or chondroid material. EOO is an extremely rare disease, accounting for only 1% of soft tissue sarcomas, and typically presents in either an extremity or the retroperitoneum. This paper presents the case of a 45-year-old Caucasian male with extraosseous osteosarcoma of the esophagus.

Purpose

Cyclin D1 (D1) is found on 11q13 which is a region frequently amplified in several tumor types. The CCND1 locus gives rise to at least two protein isoforms of D1 (D1a and D1b). A common G/A polymorphism (G/A870) is thought to influence the expression levels of D1a and D1b. D1b has been suggested to be increased in the presence of the A allele and more oncogenic than D1a. Furthermore, the A allele has been reported to correlate with increased risk of carcinoma in several tumor types suggesting that this polymorphism and D1b are important in tumor progression. However, contradictory data regarding the polymorphism, D1 variant expression, and correlation with survival have been reported. We explored the relationship between gene amplification, G/A870 genotype, D1a and D1b expression and overall survival in esophageal adenocarcinoma (EAC) and non-small cell lung cancer (NSCLC).

Experimental Design

DNA and RNA were isolated from 54 EAC samples and 89 NSCLC samples and analyzed for gene amplification, genotype at the polymorphism, gene expression, and association with overall survival.

Results

D1 variant expression did not correlate with amplification, genotype or overall survival in either tumor type. Total D1 expression correlated with decreased patient survival. Several other genes on 11q13 also appear to be overexpressed and correlated with decreased survival.

Conclusions

We report that the G/A870 polymorphism does not correlate with patient survival or with D1a or D1b expression. However, total D1 expression and expression of several other genes on 11q13 appear to be associated with EAC patient survival.

Rationale: The role of computed tomography (CT) screening for lung cancer is controversial, currently under study, and not yet fully elucidated.

Objectives: To report findings from initial and 1-year repeat screening low-radiation-dose CT of the chest and 3-year outcomes for 50- to 79-year-old current and ex-smokers in the Pittsburgh Lung Screening Study (PLuSS).

Methods: Notified of findings on screening CT, subjects received diagnostic advice from both study and personal physicians. Tracking subjects for up to three years since initial screening, we obtained medical records to document diagnostic procedures, lung cancer diagnoses, and deaths.

Measurements and Main Results: 3,642 and 3,423 subjects had initial and repeat screening. A total of 1,477 (40.6% of 3,624) were told about noncalcified lung nodules on the initial screening and, before repeat screening, 821 (55.6% of 1,477, 22.5% of 3,642) obtained one or more subsequent diagnostic imaging studies (CT, positron emission tomography [PET], or PET-CT). Tracking identified 80 subjects with lung cancer, including 53 subjects with tumor seen at initial screening. In all, 36 subjects (1.0% of the 3,642 screened), referred for abnormalities on either the initial or repeat screening, had a major thoracic surgical procedure (thoracotomy, video-assisted thoracoscopic surgery [VATS], median sternotomy, or mediastinoscopy) leading to a noncancer final diagnosis. Out of 82 subjects with thoracotomy or VATS to exclude malignancy in a lung nodule, 28 (34.1%) received a noncancer final diagnosis. Forty of 69 (58%) subjects with non–small cell lung cancer had stage I disease at diagnosis.

Conclusions: Though leading to the discovery of early stage lung cancer, CT screening also led to many diagnostic follow-up procedures, including major thoracic surgical procedures with noncancer outcomes.

Background:

Epiphrenic diverticula are rare outpouchings of the distal esophagus that infrequently require surgical intervention for the treatment of symptoms. In cases where surgical therapy is indicated, the traditional approach is through a thoracotomy. Advances in minimally invasive techniques have led to thoracoscopic and more recently laparoscopic management of epiphrenic diverticula. The purpose of this article is to review the literature on minimally invasive surgery for epiphrenic diverticula with particular attention to the operative approach and technique, surgical mortality and morbidity, and symptomatic outcomes.

Methods:

A review of the literature limited to studies in the English language and performed on humans was conducted on PubMed using the following key words: “esophageal diverticula” and “epiphrenic”. Articles retrieved by the PubMed search were reviewed.

Conclusions:

A minimally invasive approach to epiphrenic diverticula offers reduced operative mortality, decreased length of stay, and similar symptom relief compared with open surgery in the hands of experienced laparoscopic surgeons.

Objectives

Expression of micro RNAs (miRNAs) by array analysis has identified unique profiles for classifying tissues and tumors. The purpose of our study was to examine miRNA expression in Barrett’s esophagus (BE) and esophageal cancer to identify potential markers for disease progression.

Methods

miRNA was isolated from 35 frozen specimens (10 adenocarcinomas [AC], 10 squamous cell carcinomas [SCC], 9 normal epithelium [NSE], 5 BE and 1 high grade dysplasia [HGD]). miRNA expression was analyzed using Ambion Bioarrays containing 328 human miRNA probes.

Results

Unsupervised hierarchical clustering resulted in four major branches corresponding with four histologic groups. One branch consisted of 7 NSE and 1 SCC sample. The second branch of 7 SCC and 1 NSE. Third branch contained 4 BE and 1 SCC, and the fourth all the AC, and 1 each BE, NSE, SCC and the HGD. Supervised classification with Principal Component Analysis determined the NSE samples were more similar to the SCC tumors, and the BE more similar to AC. Pair-wise comparisons between sample types revealed miRNA’s which may be markers of tumor progression. mir_203 and mir_205 were expressed 2–10 fold lower in SCC and AC compared with NSE. mir_21 expression was 3–5 fold higher in both tumors versus NSE. Prediction analysis of microarray (PAM) classified 3 BE samples as BE, 1 as AC and 1 as NSE.

Conclusions

miRNA expression profiles distinguish esophageal tumor histologies and discriminate normal tissue from tumorMicroRNA expression may prove useful for identifying BE patients at high risk for progression to AC.