Does recurrent laryngeal nerve lymph node metastasis really affect the prognosis in node-positive patients with squamous cell carcinoma of the middle thoracic esophagus?

BACKGROUND: Recurrent laryngeal nerve (RLN) lymph node metastasis used to be shown a predictor for poor prognosis in esophageal squamous cell carcinoma. The purpose of this study was to evaluate the prognostic impact of RLN node metastasis and the number of metastatic lymph nodes in node-positive patients with squamous cell carcinoma of middle thoracic esophagus. METHODS: A cohort of 235 patients who underwent curative surgery for squamous cell carcinoma of middle thoracic esophagus was investigated. The prognostic impact was evaluated by univariate and multivariate analyses. RESULTS: Lymph node metastasis was found in 133 patients. Among them, 81 had metastatic RLN nodes, and 52 had at least one positive node but no RLN nodal involvement. The most significant difference in survival was detected between patients with metastatic lymph nodes below and above a cutoff value of six (P < 0.001). Multivariate analysis revealed that the number of metastatic lymph nodes was a significant factor associated with overall survival (P < 0.001), but RLN lymph node metastasis was not (P = 0.865). CONCLUSIONS: RLN Lymph node metastasis is not, but the number of metastatic nodes is a prognostic predictor in node-positive patients with squamous cell carcinoma of the middle thoracic esophagus.

Different characteristics of thymomas with and without myasthenia gravis.

BACKGROUND: The objective of this study was to evaluate the different pathological and clinical characteristics of thymomas with and without myasthenia gravis (MG) and to determine whether the presence of MG influences the prognosis in thymoma patients. METHODS: We retrospectively studied data from 228 consecutive patients operated on from 1992 to 2007 in Beijing Tongren Hospital. These thymoma patients have been subdivided into two groups: group A with MG (n = 125) and group B without MG (n = 103). RESULTS: There were no perioperative deaths. There were 19 inoperable cases (6 in the group with MG, 13 without MG, P = 0.035). The proportions of types A, AB, B1, B2, B3, and C thymoma in this data were 0, 22.4, 26.4, 30.4, 20.8, and 0%, respectively, in the group with MG, and 10.5, 13.4, 23.6, 24.5, 16.4, and 11.6%, respectively in the group without MG. There was a significant difference between hyperplastic paraneoplastic thymus coexisting in 28.8% patients with MG and only 5.8% in patients without MG. Microthymoma was identified in the paraneoplastic thymus of three patients with MG. There were 198 patients followed up. There was no recurrence in patients with type A, and a few patients with types AB, B1, B2, B3, and C recurred. The actuarial 5- and 10-year survival rates were 89.3 and 81.2% for patients with MG, respectively, and 90 and 78.9% for patients without MG, respectively. Within 5 years postoperatively, 6 of 9 patients with MG died of myasthenia crisis, while 6 of 7 deaths in patients without MG were attributable to inoperable tumors (stage IV) and type C thymoma. CONCLUSIONS: MG seldom occurs in types A and C thymoma. MG of some thymoma patients was not caused by thymoma, but by the paraneoplastic thymus. The prognosis of thymomas with MG is similar to that without MG. The main cause of death is myasthenia crisis for thymoma patients with MG and stage IV and/or type C for thymoma patients without MG.

Prognostic significance of solitary lymph node metastasis in patients with squamous cell carcinoma of middle thoracic esophagus.

BACKGROUND: The aim of this study is to compare clinical outcomes between patients with solitary lymph node metastasis and node-negative (N0) patients in squamous cell carcinoma of the middle thoracic esophagus. METHODS: A series of 135 patients with squamous cell carcinoma of the middle thoracic esophagus were retrospectively investigated. There were 33 patients with solitary lymph node metastasis and 102 N0 patients. Skip metastasis in 33 patients with solitary lymph node metastasis was defined according to three criteria: Japanese Society for Esophageal Disease (JSED), American Joint Commission on Cancer (AJCC), and the anatomical compartment. RESULTS: In 33 patients with solitary lymph node metastasis, skip metastasis was shown in 13, 23, and 8 patients according JSED, AJCC and anatomical compartment respectively. The 5-year survival rates for N0 patients and patients with solitary lymph node metastasis were 58% and 32% respectively (P =0.008). Multivariate analysis revealed that skip metastasis was not an independent prognostic factor. CONCLUSIONS: For patients with middle thoracic esophageal squamous cell carcinoma, solitary lymph node metastasis has a negative impact on survival compared with N0 disease; skip metastasis, however, is comparable to N0 diseases in predicting prognosis.

Multimodality therapy for esophageal cancer.

Recent developments in the epidemiology, staging, and treatment of esophageal and gastroesophageal junction cancers have led to significant changes in the way these malignancies are managed. Although a relationship between gastroesophageal reflux disease and esophageal cancer has been demonstrated, antireflux surgery has been shown to have no preventive effect with regard to the development of esophageal adenocarcinoma. The newly modified staging system of the World Esophageal Cancer Consortium has helped define the optimal number of lymph nodes to dissect during an esophagectomy. Incorporating modern techniques, such as esophageal ultrasound, fine needle aspiration, and positron emission tomography, can improve the prognostic value of staging. Use of higher-volume centers and higher-volume surgeons for the performance of procedures in upper gastrointestinal cancers is associated with better outcomes. Neoadjuvant chemoradiation using a wide variety of chemotherapy regimens appears to have become the new standard of care for stage II and III esophageal cancer.

Thoracoscopic sympathectomy.

With the advent of videotechnology, sympathectomy has assumed a more important role in the armamentarium of managing diseases of the autonomic system. Currently it is used primarily for hyperhydrosis, although sympathectomy for reflex sympathetic dystrophy (RSD), Raynaud disease and other diseases still are performed, but less frequently. Most of this article will refer primarily to hyperhydrosis patients.

Resection following concurrent chemotherapy and high-dose radiation for stage IIIA non-small cell lung cancer.

OBJECTIVE: Concern exists regarding surgery after thoracic radiation. We aimed to assess early results of anatomic resection following induction therapy with platinum-based chemotherapy and full-dose thoracic radiation for resectable N2+ stage IIIA non-small cell lung cancer. METHODS: Two prospective trials were recently conducted by NRG Oncology in patients with resectable N2+ stage IIIA non-small cell lung cancer with the primary end point of mediastinal node sterilization following concurrent full-dose chemoradiotherapy (Radiation Therapy Oncology Group trials 0229 and 0839). All surgeons demonstrated postinduction resection expertise. Induction consisted of weekly carboplatin (area under the curve, 2.0) and paclitaxel (50 mg/m2) and concurrent thoracic radiation 60 Gy (0839)/61.2 Gy (0229) in 30 fractions. Patients in study 0839 were randomized 2:1 to weekly panitumumab + chemoradiotherapy or chemoradiotherapy alone during induction. Primary results were similar in all treatment arms and reported previously. Short-term surgical outcomes are reported here. RESULTS: One hundred twenty-six patients enrolled; 93 (74%) had anatomic resection, 77 underwent lobectomy, and 16 underwent extended resection. Microscopically margin-negative resections occurred in 85 (91%). Fourteen (15%) resections were attempted minimally invasively, including 2 converted without event. Grade 3 or 4 surgical adverse events were reported in 26 (28%), 30-day mortality in 4 (4%) and 90-day mortality in 5 (5%). Patients undergoing extended resection experienced similar rates of grade 3 or 4 adverse events (odds ratio, 0.95; 95% confidence interval, 0.42-3.8) but higher 30-day (1.3% vs 18.8%) (odds ratio, 17.54; 95% confidence interval, 1.75-181.8) and 90-day mortality (2.6% vs 18.8%) (odds ratio, 8.65; 95% confidence interval, 1.3-56.9). CONCLUSIONS: Lobectomy was performed safely following full-dose concurrent chemoradiotherapy in these multi-institutional prospective trials; however, increased mortality was noted with extended resections.

Stage-specific therapy for cancer of the oesophagus: a new 'cancer of the elderly'.

Oesophageal and gastric cancers are amongst the most frequent and lethal of cancers worldwide. In the US alone, some 13 000 individuals are affected each year, and mortality is particularly high in elderly patients with advanced stage disease and multiple co-morbidities. Patients usually do not present until later in the disease when symptoms occur, once the tumour is sufficiently large to cause obstruction or invasion of adjacent structures. Oesophageal cancer can metastasize to almost any organ, and widespread distant metastases are almost always present at the time of death. Overall mortality from this cancer is around 80-90%. Curative treatment of oesophageal cancer must achieve local control of the primary lesion as well as control and/or prevention of metastases. These are important contributors to overall results when therapy is undertaken in elderly patients, as are the significant risks of adverse effects such as morbidity from chemoradiation and the morbidity and mortality of oesophagectomy. Surgical resection affords the best chance for local control and the best means of palliation of dysphagia for most patients with localized disease, although both local and systemic recurrence of disease are common when surgery is used alone. Because of the low cure rates associated with the use of surgery alone, other modalities have been added to the treatment regimen. Elderly patients with significant cardiac and pulmonary co-morbidity are candidates for nonoperative therapy, even at an early disease stage. There are few data to support a survival advantage from adjuvant radiotherapy or chemotherapy following complete resection, in the absence of documented metastatic disease. Chemotherapy and radiotherapy have both been reported to improve survival when administered preoperatively in patients with oesophageal cancer, while current data using trimodal therapy show a trend towards increased treatment-related mortality with only a slight increase in overall survival. There is currently no completely reliable preoperative method for restaging patients following neoadjuvant chemoradiation in order to assess pathological complete response. Novel restaging techniques are therefore required, in addition to further study of the risks and benefits of neoadjuvant chemoradiotherapy for this disease.

The role of thoracoscopy in the management of cancer patients.

Thoracoscopy or video-assisted thoracic surgery (VATS) has become an important tool in the management of thoracic diseases. Most thoracic procedures are first attempted using a VATS technique. Thoracoscopy has an important role in managing malignancies that present with symptoms or lesions in the chest. Although the primary role is diagnostic, in the case of non-thoracic malignancies, VATS also has an important palliative treatment role, as in dealing with pleural and pericardial effusions and metastatic deposits.

Long-term survival in patients with synchronous, solitary brain metastasis from non-small-cell lung cancer treated with radiosurgery.

PURPOSE: To report the outcome of patients with synchronous, solitary brain metastasis from non-small-cell lung cancer (NSCLC) treated with gamma knife stereotactic radiosurgery (GKSRS). PATIENTS AND METHODS: Forty-two patients diagnosed with synchronous, solitary brain metastasis from NSCLC were treated with GKSRS between 1993 and 2006. The median Karnofsky performance status (KPS) was 90. Patients had thoracic Stage I-III disease (American Joint Committee on Cancer 2002 guidelines). Definitive thoracic therapy was delivered to 26/42 (62%) patients; 9 patients underwent chemotherapy and radiation, 12 patients had surgical resection, and 5 patients underwent preoperative chemoradiation and surgical resection. RESULTS: The median overall survival (OS) was 18 months. The 1-, 2-, and 5-year actuarial OS rates were 71.3%, 34.1%, and 21%, respectively. For patients who underwent definitive thoracic therapy, the median OS was 26.4 months compared with 13.1 months for those who had nondefinitive therapy, and the 5-year actuarial OS was 34.6% vs. 0% (p < 0.0001). Median OS was significantly longer for patients with a KPS >or=90 vs. KPS < 90 (27.8 months vs. 13.1 months, p < 0.0001). The prognostic factors significant on multivariate analysis were definitive thoracic therapy (p = 0.020) and KPS (p = 0.001). CONCLUSIONS: This is one of the largest series of patients diagnosed with synchronous, solitary brain metastasis from NSCLC treated with GKSRS. Definitive thoracic therapy and KPS significantly impacted OS. The 5-year OS of 21% demonstrates the potential for long-term survival in patients treated with GKSRS; therefore, patients with good KPS should be considered for definitive thoracic therapy.

Less efficient g2-m checkpoint is associated with an increased risk of lung cancer in African Americans.

Cell cycle checkpoints play critical roles in the maintenance of genomic integrity. The inactivation of checkpoint genes by genetic and epigenetic mechanisms is frequent in all cancer types, as a less-efficient cell cycle control can lead to genetic instability and tumorigenesis. In an on-going case-control study consisting of 216 patients with non-small cell lung cancer, 226 population-based controls, and 114 hospital-based controls, we investigated the relationship of gamma-radiation-induced G2-M arrest and lung cancer risk. Peripheral blood lymphocytes were cultured for 90 hours, exposed to 1.0 Gy gamma-radiation, and harvested at 3 hours after gamma-radiation treatment. gamma-Radiation-induced G2-M arrest was measured as the percentage of mitotic cells in untreated cultures minus the percentage of mitotic cells in gamma-radiation-treated cultures from the same subject. The mean percentage of gamma-radiation-induced G2-M arrest was significantly lower in cases than in population controls (1.18 versus 1.44, P < 0.01) and hospital controls (1.18 versus 1.40, P = 0.01). When dichotomized at the 50th percentile value in combined controls (population and hospital controls), a lower level of gamma-radiation-induced G2-M arrest was associated with an increased risk of lung cancer among African Americans after adjusting for baseline mitotic index, age, gender, and pack-years of smoking [adjusted odd ratio (OR), 2.25; 95% confidence interval (95% CI), 0.97-5.20]. A significant trend of an increased risk of lung cancer with a decreased level of G2-M arrest was observed (P(trend) = 0.02) among African Americans, with a lowest-versus-highest quartile adjusted OR of 3.74 (95% CI, 0.98-14.3). This trend was most apparent among African American females (P(trend) < 0.01), with a lowest-versus-highest quartile adjusted OR of 11.75 (95% CI, 1.47-94.04). The results suggest that a less-efficient DNA damage-induced G2-M checkpoint is associated with an increased risk of lung cancer among African Americans. Interestingly, we observed a stronger association of DNA damage-induced G2-M arrest and lung cancer among African Americans when compared with Caucasians. If replicated, these results may provide clues to the exceedingly high lung cancer incidence experienced by African Americans.

Inactivation of p16, RUNX3, and HPP1 occurs early in Barrett's-associated neoplastic progression and predicts progression risk.

Patients with Barrett's esophagus (BE) are at increased risk of developing esophageal adenocarcinoma (EAC). Clinical neoplastic progression risk factors, such as age and the length of the esophageal BE segment, have been identified. However, improved molecular biomarkers predicting increased progression risk are needed for improved risk assessment and stratification. Using real-time quantitative methylation-specific PCR, we screened 10 genes (HPP1, RUNX3, RIZ1, CRBP1, 3-OST-2, APC, TIMP3, p16, MGMT, p14) for promoter hypermethylation in 77 EAC, 93 BE, and 64 normal esophagus (NE) specimens. A subset of genes manifesting significant differences in methylation frequencies between BE and EAC was then analysed in 20 dysplastic specimens. All 10 genes except p14 were frequently methylated in EACs, with RUNX3, HPP1, CRBP1, RIZ1, and OST-2 representing novel methylation targets in EAC and/or BE. p16, RUNX3, and HPP1 displayed increasing methylation frequencies in BE vs EAC. Furthermore, these increases in methylation occurred early, at the interface between BE and low-grade dysplasia (LGD). To demonstrate the silencing effect of hypermethylation, we selected the EAC cells BIC1, in which the HPP1 promoter is natively methylated, and subjected them to 5-aza-2'-deoxycytidine (Aza-C) treatment. Real-time RT-PCR indicated increased HPP1 mRNA levels after 3 days of Aza-C treatment, as well as decreased levels of methylated HPP1 DNA. Hypermethylation of a subset of six genes (APC, TIMP3, CRBP1, p16, RUNX3, and HPP1) was then tested in a retrospective longitudinal study of 99 BE and nine LGD specimens obtained from 53 BE patients undergoing surveillance endoscopy. Only high-grade dysplasia (HGD) or EAC were defined as progression end points. Two patient groups were compared: eight progressors (P) and 45 nonprogressors (NP), using Cox proportional hazards models to determine the relative progression risks of age, BE segment length, and methylation events. Multivariate analyses revealed that only hypermethylation of p16 (odds ratio (OR) 1.74, 95% confidence interval (CI) 1.33-2.20), RUNX3 (OR 1.80, 95% CI 1.08-2.81), and HPP1 (OR 1.77, 95% CI 1.06-2.81) were independently associated with an increased risk of progression, whereas age, BE segment length, and hypermethylation of TIMP3, APC, or CRBP1 were not independent risk factors. In combined analyses, risk was detectable up to, but not earlier than, 2 years preceding neoplastic progression. Hypermethylation of p16, RUNX3, and HPP1 in BE or LGD may represent independent risk factors for the progression of BE to HGD or EAC. These findings have implications regarding risk stratification, early EAC detection, and the appropriate endoscopic surveillance interval for patients with BE.

Outcome results of the 1996-1999 patterns of care survey of the national practice for patients receiving radiation therapy for carcinoma of the esophagus.

PURPOSE: A Patterns of Care Study of patients treated from 1996 to 1999 evaluated the national practice for patients receiving radiation therapy for carcinoma of the esophagus in the United States. METHODS: A national survey was conducted at 59 institutions in a stratified random sample selected from a master list of radiation therapy facilities throughout the United States. Patient, tumor, and treatment characteristics were evaluated. Multivariate comparisons of survival times were made using the Cox proportional hazards model. RESULTS: Adenocarcinoma was diagnosed in 51% of patients and squamous cell carcinoma in 49% of patients. Sixteen percent of patients were clinical stage (CS) I (using the 1983 American Joint Committee on Cancer system), 39% were CS II, and 33% were CS III. Significant variables in the multivariate analysis of survival times included clinical stage, treatment approach, and facility size. Patients with CS III disease had a higher hazard risk of death as compared with CS I patients (hazard ratio [HR], 2.01; P = .001), whereas those treated with chemoradiotherapy followed by surgery (HR, 0.32; P < .0001) had a decreased risk of death compared with chemoradiotherapy-only patients. Patients at small centers had a higher risk of death (HR, 1.32; P = .03) compared with patients treated at larger facilities. CONCLUSION: Concurrent chemoradiotherapy continued to be the most commonly utilized treatment approach during the time period studied. The observation that patients undergoing surgical resection following chemoradiation have a decreased HR or chance of death compared with other treatment schemes supports the need for a randomized trial comparing these strategies.

Nerve injury: injury to the recurrent laryngeal, phrenic, vagus, long thoracic, and sympathetic nerves during thoracic surgery.

Nerve injury occurs in about 1% of patients undergoing thoracic surgery. Most commonly, it is the result of surgical trauma specific to the area of operation. Alternatively, it may be due to retraction on adjacent structures during the exposure of complex surgical procedures. This article reviews the most common types of nerve injury and discusses the pathophysiology, etiology, diagnosis, and treatment of each.

Artificial neural networks and gene filtering distinguish between global gene expression profiles of Barrett's esophagus and esophageal cancer.

cDNAmicroarrays, combined with bioinformatics analyses, are becomingincreasingly used in current medical research. Existing analytic methods,particularly those that are unsupervised, often have difficulty recognizing subtle differences among predefined subgroups. In contrast, supervised methods, such as Artificial Neural Networks (ANNs), are able to recognize subtly different biological entities. We applied ANNs in a proof-of-principle study of cDNA microarray data in esophageal cancer (CA) and premalignancy. cDNA microarrays, each containing 8064 clones, were hybridized to RNAs from 22 esophageal lesions, including 14 Barrett's esophagus (BA) metaplasias and 8 esophageal carcinomas (3 squamous cell carcinomas and 5 adenocarcinomas). Scanned cDNA microarray data were analyzed using the bioinformatics software Cluster/TreeView, Significance Analysis of Microarrays (SAM), and ANNs. Cluster analysis based on all 8064 clones on the microarrays was unable to correctly distinguish BA specimens from CA specimens. SAM then selected 160 differentially expressed genes between Barrett's and cancer. Cluster analysis based on this reduced set still misclassified 2 Barrett's as cancers. The ANN was trained on 12 samples and tested against the remaining 10 samples. Using the 160 selected genes, the ANN correctly diagnosed all 10 samples in the test set. Finally, the 160 genes selected by SAM may merit further study as biomarkers of neoplastic progression in the esophagus, as well as in elucidating pathological mechanisms underlying BA and CA.

Local Therapy Indications in the Management of Patients with Oligometastatic Non-Small Cell Lung Cancer.

Advances in surgical, radiation, and interventional radiology therapies carry a reduction in morbidity associated with therapy. Aggressive management of patients with oligometastatic non-small cell lung cancer offers the potential for improved disease-free survival and quality of life compared with traditional systemic therapy alone.

Less Common Side Effects of Sympathetic Surgery.

Because of video-assisted thoracic technology and increased patient awareness of treatment options for palmar hyperhidrosis, endoscopic thoracic sympathectomy (ETS) has become a well-accepted treatment for this disorder. Video assistance affords excellent visualization of thoracic anatomy, which allows the procedure to be done quickly with few complications. However, despite the ease of performing ETS, complications can occur unless thoracic anatomy and physiology are well-understood. Awareness of possible intraoperative and postoperative complications is essential if this procedure is gong to be performed safely.

Epidemiology of Lung Cancer.

Lung cancer has been transformed from a rare disease into a global problem and public health issue. The etiologic factors of lung cancer become more complex along with industrialization, urbanization, and environmental pollution around the world. Currently, the control of lung cancer has attracted worldwide attention. Studies on the epidemiologic characteristics of lung cancer and its relative risk factors have played an important role in the tertiary prevention of lung cancer and in exploring new ways of diagnosis and treatment. This article reviews the current evolution of the epidemiology of lung cancer.

Stereotactic Body Radiotherapy and Ablative Therapies for Lung Cancer.

The treatment paradigm for early stage lung cancer and oligometastatic disease to the lung is rapidly changing. Ablative therapies, especially stereotactic body radiation therapy, are challenging the surgical gold standard and have the potential to be the standard for operable patients with early stage lung cancer who are high risk due to co- morbidities. The most commonly used ablative modalities include stereotactic body radiation therapy, microwave ablation, and radiofrequency ablation.

Stage-directed individualized therapy in esophageal cancer.

Esophageal cancer is the eighth most common cancer worldwide, and the incidence of esophageal carcinoma is rapidly increasing. With the advent of new staging and treatment techniques, esophageal cancer can now be managed through various strategies. A good understanding of the advances and limitations of new staging techniques and how these can guide in individualizing treatment is important to improve outcomes for esophageal cancer patients. This paper outlines the recent progress in staging and treatment of esophageal cancer, with particularly attention to endoscopic techniques for early-stage esophageal cancer, multimodality treatment for locally advanced esophageal cancer, assessment of response to neoadjuvant treatment, and the role of cervical lymph node dissection. Furthermore, advances in robot-assisted surgical techniques and postoperative recovery protocols that may further improve outcomes after esophagectomy are discussed.

Deploying Team Science Principles to Optimize Interdisciplinary Lung Cancer Care Delivery: Avoiding the Long and Winding Road to Optimal Care.

The complexity of lung cancer care mandates interaction between clinicians with different skill sets and practice cultures in the routine delivery of care. Using team science principles and a case-based approach, we exemplify the need for the development of real care teams for patients with lung cancer to foster coordination among the multiple specialists and staff engaged in routine care delivery. Achieving coordinated lung cancer care is a high-priority public health challenge because of the volume of patients, lethality of disease, and well-described disparities in quality and outcomes of care. Coordinating mechanisms need to be cultivated among different types of specialist physicians and care teams, with differing technical expertise and practice cultures, who have traditionally functioned more as coactively working groups than as real teams. Coordinating mechanisms, including shared mental models, high-quality communication, mutual trust, and mutual performance monitoring, highlight the challenge of achieving well-coordinated care and illustrate how team science principles can be used to improve quality and outcomes of lung cancer care. To develop the evidence base to support coordinated lung cancer care, research comparing the effectiveness of a diverse range of multidisciplinary care team approaches and interorganizational coordinating mechanisms should be promoted.