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2.
J Clin Immunol ; 33(5): 896-902, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23584561

ABSTRACT

PURPOSE: Autosomal dominant hyper-IgE syndrome (AD-HIES) due to heterozygous STAT3 mutation is a primary immunodeficiency characterized by eczema, elevated serum IgE, recurrent infections, and connective tissue and skeletal findings. Healing of pneumonias is often abnormal with formation of pneumatoceles and bronchiectasis. We aimed to explore whether healing after lung surgery is also aberrant. METHODS: We retrospectively analyzed the medical records of 32 patients with AD-HIES who received lung surgery for the management of pulmonary infections from 1960 to 2011. We collected information including patient demographics, STAT3 mutation status, clinical history, surgical and medical procedures performed, complications, related medical treatments, and outcomes. RESULTS: More than 50% of lung surgeries had associated complications, with the majority being prolonged bronchopleural fistulae. These fistulae often led to empyemas that necessitated additional interventions including prolonged antibiotics, prolonged thoracostomy tube drainage and re-operations. CONCLUSION: Lung surgery in AD-HIES patients is associated with high complication rates. STAT3 mutations likely lead to abnormalities in tissue remodelling that are further exacerbated by infection.


Subject(s)
Job Syndrome/immunology , Job Syndrome/physiopathology , Lung Diseases/physiopathology , Lung Diseases/surgery , Wound Healing/physiology , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Lung/immunology , Lung/physiopathology , Lung/surgery , Lung Diseases/genetics , Lung Diseases/immunology , Male , Middle Aged , Mutation , Retrospective Studies , STAT3 Transcription Factor/genetics , Wound Healing/genetics , Young Adult
4.
Biomaterials ; 34(12): 2980-90, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23369215

ABSTRACT

The cell membrane is a critical barrier to effective delivery for many therapeutics, including those which are nanoparticle-based. Improving nanoparticle transport across the cell membrane remains a fundamental challenge. Cancer cells preferentially internalized pegylated calcium phosphate nanoparticles over normal epithelial cells. Furthermore, non-cytotoxic levels of doxorubicin markedly amplified this difference by increasing free unbound caveolin-1 and resulted in enhanced caveolin-mediated nanoparticle endocytosis in cancer cells. Engineered pegylated siRNA-loaded triple-shell calcium phosphate nanoconstructs incorporating ultra-low levels of doxorubicin recapitulated these effects and delivered increased numbers of siRNA into cancer cells with target-specific results. Systemic administration of nanoparticles in vivo demonstrated highly preferential entry into tumors, little bystander organ biodistribution, and significant tumor growth arrest. In conclusion, siRNA-loaded calcium phosphate nanoparticles incorporating non-cytotoxic amounts of doxorubicin markedly enhances nanoparticle internalization and results in increased payload delivery with concomitant on-target effects.


Subject(s)
Calcium Phosphates/administration & dosage , Endocytosis , Nanoparticles , Neoplasms/metabolism , Polyethylene Glycols/chemistry , RNA, Small Interfering/chemistry , Base Sequence , Cell Line, Tumor , Cells, Cultured , DNA Primers , Doxorubicin/administration & dosage , Humans , Microscopy, Confocal , Microscopy, Electron , Neoplasms/pathology , RNA, Small Interfering/administration & dosage , Reactive Oxygen Species/metabolism , Real-Time Polymerase Chain Reaction
5.
J Thorac Oncol ; 8(2): 246-9, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23328550

ABSTRACT

INTRODUCTION: Although thymic epithelial tumors (TETs) commonly infiltrate mediastinal structures, cardiac involvement is uncommon and has not been systematically studied. The purpose of this study was to describe our single-institution experience of the clinical presentation, treatment, and follow-up of cardiac involvement in patients with TETs. METHODS: A single-institution retrospective review of cardiac involvement among patients with TETs from 2008 to 2012. RESULTS: The frequency of cardiac involvement was 4%. All five patients with confirmed cardiac disease had left heart involvement. Only one patient was symptomatic. Myocardial invasion was the most common mode of involvement followed by transvenous spread. Surgical resection of the involved area was attempted in three patients: in one, surgery was aborted because of extensive myocardial involvement; in the other two patients, resection was incomplete. Surgery averted a potentially catastrophic hemodynamic complication in one patient. However, cardiac tumor recurred in both patients who underwent incomplete resection. One patient underwent radiation therapy resulting in complete regression of an aortic root mass. CONCLUSIONS: This study represents the most comprehensive review of cardiac involvement in patients with TETs. In contrast to previous single-case reports, we found a preponderance of asymptomatic presentation, left heart involvement, and myocardial invasion. Dynamic cardiovascular magnetic resonance imaging should be considered in cases when cardiac involvement is suspected. Although immediate surgical resection is indicated for impending hemodynamic compromise, long-term palliation with surgery for myocardial involvement seems poor, especially when complete resection cannot be performed. Radiation therapy should be considered in selected patients.


Subject(s)
Heart Neoplasms/etiology , Neoplasm Recurrence, Local/etiology , Neoplasms, Glandular and Epithelial/complications , Thymus Neoplasms/complications , Adult , Female , Follow-Up Studies , Heart Neoplasms/pathology , Heart Neoplasms/surgery , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Neoplasm Staging , Neoplasms, Glandular and Epithelial/pathology , Neoplasms, Glandular and Epithelial/surgery , Prognosis , Retrospective Studies , Thymus Neoplasms/pathology , Thymus Neoplasms/surgery
7.
J Clin Endocrinol Metab ; 97(7): 2223-30, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22508705

ABSTRACT

CONTEXT: ACTH-producing neuroendocrine tumor (NET) of the thymus is a rare cause of Cushing's syndrome (CS). The literature consists mainly of isolated case reports. PATIENTS: We studied 12 cases (eight males and four females) diagnosed between 1986 and 2010 with CS and thymic NET who underwent surgical resection. MAIN OUTCOME MEASURES: We measured time from onset of CS to diagnosis of thymic NET, tumor size, histological grade, time to recurrence, and survival and performed a meta-analysis of other published cases of CS associated with thymic NET. RESULTS: Eleven of 12 patients presented with classic features of CS at a median age of 21 yr (range, 7-51). Four were children. The 24-h urine free cortisol was greater than 16-fold of normal, and biochemical testing was consistent with ectopic ACTH production in all 11. Another patient presenting with pulmonary embolus had a thymic mass and was later diagnosed with CS. All patients underwent thymectomy, and nine of 10 tumors exhibited positive ACTH immunochemistry. Median tumor diameter was 5 cm (range, 1-11.5). Six patients recurred 20-28 months after surgery with metastases to mediastinal lymph nodes (n = 5), bone (n = 5), liver (n = 1), parotid gland (n = 1), and breast (n = 1). Four of five patients treated with radiation therapy also received chemotherapy. All recurrent patients received ketoconazole; four later underwent bilateral adrenalectomy. Six recurrent patients died 22-90 months (median, 57) after thymectomy. At last review, six patients were alive 14-90 months (median, 49) after thymectomy. These data are similar to those from the meta-analysis. CONCLUSIONS: Thymic ACTH-producing NET is an aggressive disease that should be considered in CS with ectopic ACTH secretion, particularly in younger patients.


Subject(s)
ACTH Syndrome, Ectopic/surgery , Neuroendocrine Tumors/surgery , Thymus Neoplasms/surgery , ACTH Syndrome, Ectopic/diagnosis , Adolescent , Adult , Child , Cohort Studies , Cushing Syndrome/diagnosis , Cushing Syndrome/etiology , Cushing Syndrome/surgery , Female , Humans , Male , Middle Aged , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/metabolism , Retrospective Studies , Thymectomy , Thymus Neoplasms/diagnosis , Thymus Neoplasms/metabolism , Time Factors , Young Adult
8.
J Thorac Cardiovasc Surg ; 140(6): 1276-82, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20584535

ABSTRACT

OBJECTIVES: Although refractory to chemotherapy, metastatic melanoma may respond to adoptive immunotherapy. As novel treatments evolve, surgeons may be asked to perform metastasectomy not only for palliation or potential cure but also for isolation of tumor-infiltrating lymphocytes. This study was undertaken to examine outcomes of patients with melanoma undergoing thoracic metastasectomy in preparation for investigational immunotherapy. METHODS: A retrospective review identified 107 consecutive patients who underwent 116 thoracic metastasectomy procedures from April 1998 to July 2009. Indications for surgical intervention included procurement of tumor-infiltrating lymphocytes, rendering of patients to no evaluable disease status, palliation, and diagnosis. Response Evaluation Criteria in Solid Tumors criteria were used to assess tumor response. RESULTS: Thoracotomy, lobectomy, and video-assisted thoracoscopic surgery with nonanatomic resection were the most common procedures. Major complications included 1 death and 1 coagulopathy-induced hemothorax. Seventeen patients were rendered to no evaluable disease status. Virtually all patients with residual disease had tumor specimens cultured for tumor-infiltrating lymphocytes; approximately 70% of tumor-infiltrating lymphocyte cultures exhibited antitumor reactivity. Of the 91 patients with residual or recurrent disease, 24 (26%) underwent adoptive cell transfer of tumor-infiltrating lymphocytes, of whom 7 exhibited objective responses (29% response rate and 8% based on intent to treat). Rapid disease progression precluded tumor-infiltrating lymphocyte therapy in most cases. Actuarial 1- and 5-year survival rates for patients rendered to no evaluable disease status or receiving or not receiving tumor-infiltrating lymphocytes were 93% and 76%, 64% and 33%, and 43% and 0%, respectively. CONCLUSIONS: Relatively few patients currently having thoracic metastasectomy undergo adoptive cell transfer. Continued refinement of tumor-infiltrating lymphocyte expansion protocols and improved patient selection might increase the number of patients with melanoma benefiting from these interventions.


Subject(s)
Immunotherapy, Adoptive/methods , Melanoma/surgery , Melanoma/therapy , Adolescent , Adult , Aged , Combined Modality Therapy , Female , Humans , Male , Melanoma/secondary , Middle Aged , Palliative Care , Postoperative Complications/epidemiology , Retrospective Studies , Risk Factors , Survival Rate , Thoracic Surgery, Video-Assisted , Thoracotomy , Treatment Outcome
9.
Ann Thorac Surg ; 89(1): 200-6; discussion 206, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20103235

ABSTRACT

BACKGROUND: We studied the clinical characteristics and outcomes of patients undergoing pneumonectomy after preoperative concurrent chemoradiation for non-small cell lung cancer. METHODS: Clinical records of patients with non-small cell lung cancer who underwent pneumonectomy at our institution between 1995 and 2005 after preoperative concurrent chemoradiation were reviewed retrospectively. RESULTS: Twenty-nine patients underwent pneumonectomy after preoperative concurrent chemoradiation. Of the 21 men and 8 women who were treated, 1 had stage IIB (T3N0M0) and the remainder had stage IIIA or IIIB non-small cell lung cancer. Mean patient age at surgery was 53.4 years. There were 15 right pneumonectomies, of which 2 were for pancoast tumors. All patients received concurrent preoperative chemoradiation. Mean total radiation dose was 61.1 Gy. All patients went on to have complete (R0) resection by pneumonectomy. Pathologic complete response was found in 16 patients (55.2%). All patients were discharged alive from the hospital after pneumonectomy. Median hospital length of stay was 5 days (mean 8.6). Ninety-day mortality after surgery was 3.4% (n = 1). Recurrences have been found in 11 patients (38%), including brain metastases (n = 6), bone metastases (n = 4), liver metastases (n = 2), and cervical lymph node metastases (n = 2). One patient had a contralateral new primary lung cancer develop 70 months after undergoing pneumonectomy. Estimated 5-year disease-free survival is 48%. Median survival time has not been reached. CONCLUSIONS: Pneumonectomy can be performed safely after preoperative concurrent chemoradiation, even with high-dose radiation. The frequency of disease recurrence in the brain underscores the need to evaluate the role of prophylactic cranial radiation in non-small cell lung cancer.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/surgery , Lung Neoplasms/surgery , Pneumonectomy/methods , Adult , Aged , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/radiotherapy , Disease-Free Survival , Female , Follow-Up Studies , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/radiotherapy , Male , Middle Aged , Radiation Dosage , Radiotherapy, Adjuvant , Retrospective Studies , Treatment Outcome
10.
Trials ; 10: 121, 2009 Dec 23.
Article in English | MEDLINE | ID: mdl-20030854

ABSTRACT

BACKGROUND: The standard of care for metastatic gastric cancer (MGC) is systemic chemotherapy which leads to a median survival of 6-15 months. Survival beyond 3 years is rare. For selected groups of patients with limited MGC, retrospective studies have shown improved overall survival following gastrectomy and metastasectomies including peritoneal stripping with continuous hyperthermic peritoneal perfusion (CHPP), liver resection, and pulmonary resection. Median survival after liver resection for MGC is up to 34 months, with a five year survival rate of 24.5%. Similarly, reported median survival after pulmonary resection of MGC is 21 months with long term survival of greater than 5 years a possibility. Several case reports and small studies have documented evidence of long-term survival in select individuals who undergo CHPP for MGC. DESIGN: The GYMSSA trial is a prospective randomized trial for patients with MGC. It is designed to compare two therapeutic approaches: gastrectomy with metastasectomy plus systemic chemotherapy (GYMS) versus systemic chemotherapy alone (SA). Systemic therapy will be composed of the FOLFOXIRI regimen. The aim of the study is to evaluate overall survival and potential selection criteria to determine those patients who may benefit from surgery plus systemic therapy. The study will be conducted by the Surgery Branch at the National Cancer Institute (NCI), National Institutes of Health (NIH) in Bethesda, Maryland. Surgeries and followup will be done at the NCI, and chemotherapy will be given by either the local oncologist or the medical oncology branch at NCI. TRIAL REGISTRATION: ClinicalTrials.gov ID. NCT00941655.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Gastrectomy , Hyperthermia, Induced/methods , Stomach Neoplasms , Camptothecin/analogs & derivatives , Camptothecin/therapeutic use , Combined Modality Therapy , Fluorouracil/therapeutic use , Hepatectomy , Humans , Leucovorin/therapeutic use , Organoplatinum Compounds/therapeutic use , Peritoneum/surgery , Pneumonectomy , Stomach Neoplasms/drug therapy , Stomach Neoplasms/secondary , Stomach Neoplasms/surgery , Survival Rate
11.
Ann Thorac Surg ; 86(3): 903-10, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18721580

ABSTRACT

BACKGROUND: We have previously demonstrated that high-dose chemoradiotherapy followed by resection for patients selected on the basis of mediastinal sterilization was feasible and resulted in excellent outcomes. This study was designed to determine the ability to intensify our prior approach utilizing hyperfractionated radiation and more aggressive consolidative chemotherapy. METHODS: Patients with documented stage IIIA/B nonsmall-cell lung cancer, performance status 0 to 2, and adequate organ function were eligible. A phase I portion utilized escalating doses of carboplatin and vinorelbine, commencing with areas under the curve of 1 and 5 mg/m(2), respectively, and concurrent 69.6 Gy hyperfractionated radiotherapy. A phase II portion utilized the identical radiotherapy with carboplatin/vinorelbine at the maximum tolerated dose established in phase I. Patients for whom mediastinal nodal clearance was demonstrated underwent resection. All patients were to receive consolidation chemotherapy consisting of carboplatin/vinorelbine for three cycles, followed by docetaxel for three cycles. Prophylactic cranial irradiation was offered to patients after completion of therapy. RESULTS: Forty-seven patients participated in the study (33 IIIA, 14 IIIB; 15 men, 32 women; median age, 56 years). The maximum tolerated dose for concurrent carboplatin/vinorelbine and hyperfractionated radiotherapy was established at areas under the curve of 1 and 10 mg/m(2), respectively. Twenty-eight patients completed trimodality treatment including surgery. Median survival time for the entire study cohort (n = 47) is 29.6 months, and it is 55.8 months for patients with mediastinal clearance who underwent resection (n = 28). CONCLUSIONS: Surgical resection of locally advanced stage IIIA and IIIB nonsmall-cell lung cancer after induction hyperfractionated radiation and concurrent chemotherapy is safe and well tolerated. Whether this approach is superior to less aggressive therapy is uncertain and will require comparative studies.


Subject(s)
Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/therapy , Adult , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/administration & dosage , Combined Modality Therapy , Dose Fractionation, Radiation , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Vinblastine/administration & dosage , Vinblastine/analogs & derivatives , Vinorelbine
12.
Ann Thorac Surg ; 85(2): 390-3; discussion 393-4, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18222231

ABSTRACT

BACKGROUND: The primary goal of this study is to identify clinical variables associated with successful surgical treatment for hyperhidrosis and facial blushing. METHODS: Six hundred eight thoracoscopic sympathicotomies were performed in 304 patients. Retrospective stratified analysis of patients after thoracoscopic sympathicotomy for hyperhidrosis or facial blushing and having completed follow-up of at least 6 months (n = 232) was performed. Preoperative and postoperative quality-of-life indices (range, 0 to 3) were used to measure impact of surgery, and comparisons were indexed to preoperative symptoms. Postoperative compensatory sweating was analyzed with respect to the level(s) of sympathetic chain division. RESULTS: Thoracoscopic sympathicotomy was performed at level T2 alone in 5% of patients; levels T2 to T3 in 63% of patients; levels T3 to T4 in 3% of patients; levels T2 to T4 in 14% of patients; and more than three levels in 14% of patients. In hyperhidrosis patients, mean preoperative quality-of-life index was 2.0 and postoperative quality-of-life index was 0.4 (p < 0.001). Facial blushers had preoperative and postoperative quality-of-life index of 2.6 and 1.0, respectively. Significant compensatory sweating was seen in 33% patients overall and occurred in 29% of patients with palmar symptoms, 26% of axillary patients, and 42% of facial blushers. Significant compensatory sweating in relation to the level(s) of sympathetic chain division occurred in T2 alone, 45%; T2 to T3, 30%; T3 to T4, 14%; T2 to T4, 38%; and more than three levels, 49%. CONCLUSIONS: Significant improvement in quality of life can result from surgery for hyperhidrosis. However, the incidence of postoperative compensatory sweating may be dependent on the level of sympathicotomy performed. The choice of sympathicotomy level(s) should be directed toward reducing the incidence of significant compensatory sweating while simultaneously ensuring relief of primary preoperative symptoms.


Subject(s)
Hyperhidrosis/diagnosis , Hyperhidrosis/surgery , Quality of Life , Thoracic Surgery, Video-Assisted/methods , Adolescent , Adult , Aged , Child , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Patient Satisfaction , Probability , Retrospective Studies , Risk Assessment , Severity of Illness Index , Thoracic Nerves/surgery , Thoracoscopy/methods , Treatment Outcome
13.
Thorac Surg Clin ; 16(4): 311-5, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17240818

ABSTRACT

BE is a prevalent condition often associated with long-standing and severe GERD. BE harbors the cellular and genetic substrates necessary for subsequent development of cancer in a subset of patients. Epidemiologically, BE patients with high-grade dysplasia exhibits the highest risk for cancer. Until recently, little was understood about which BE patients with no or low-grade dysplasia may also be at risk for progression to neoplasia. The presence of p53 abnormalities in Barrett's mucosae (such as 17p LOH) and also DNA abnormalities (such as aneuploidy and increased tetraploid fractions) detectable on flow cytometry may be useful in identifying those patients with BE who are at the highest risk for cancer development. New diagnostic modalities and therapeutic strategies continue to evolve, and will require careful clinical validation.


Subject(s)
Barrett Esophagus/diagnosis , Aneuploidy , Barrett Esophagus/genetics , Esophagoscopy , Flow Cytometry , Humans , Loss of Heterozygosity , Mutation , Tumor Suppressor Protein p53/genetics
14.
Ann Thorac Surg ; 80(3): 1063-6; discussion 1066, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16122487

ABSTRACT

BACKGROUND: The purpose of this study is to evaluate the safety and efficacy of thoracoscopic sympathectomy for the treatment of hyperhidrosis, blushing, reflex sympathetic dystrophy, and digital ischemia. METHODS: We conducted a retrospective review of 202 patients who underwent thoracoscopic sympathectomy at the University of Maryland from March 1992 to April 2003. RESULTS: Three hundred ninety-seven procedures were performed on 202 patients (105 women, 97 men). Mean age was 29 years (range, 9 to 65). Indications for surgery included hyperhidrosis, facial blushing, digital ischemia, and reflex sympathetic dystrophy. Synchronous bilateral sympathectomies were performed in 194 patients; right side alone (n = 6); left side alone (n = 1); 1 patient had staged bilateral sympathectomies. Single incision with lung isolation technique was used. There was no mortality. Preoperative symptoms resolved completely or significantly improved in greater than 90% of patients. One patient with reflex sympathetic dystrophy recurred and 1 patient with hyperhidrosis complained of significant compensatory sweating. Compensatory sweating to a lesser degree occurred in approximately one third of patients. Complications included asymptomatic pleural effusion (n = 1), pneumothorax (n = 1), and reoperation for chylothorax that was identified early (n = 1). In 2 patients treated for facial blushing, Horner's syndrome developed postoperatively; 1 of them subsequently underwent blepharoplasty. In 3 patients, hyperesthesias developed at the incision. CONCLUSIONS: Thoracoscopic sympathectomy can be performed safely and with excellent results. Compensatory sweating is the main side effect, although significant complaints from this are rare. Horner's syndrome remains an extremely uncommon complication as a result of thoracoscopic sympathectomy at our institution.


Subject(s)
Sympathectomy/statistics & numerical data , Thoracoscopy/statistics & numerical data , Adolescent , Adult , Aged , Baltimore , Child , Chylothorax/etiology , Female , Horner Syndrome/etiology , Humans , Hyperesthesia/etiology , Hyperhidrosis/etiology , Male , Middle Aged , Outcome and Process Assessment, Health Care , Pleural Effusion/etiology , Pneumothorax/etiology , Quality of Life , Reoperation/statistics & numerical data , Retrospective Studies , Sympathectomy/adverse effects , Sympathectomy/methods , Thoracoscopy/adverse effects , Thoracoscopy/methods , Treatment Outcome
15.
Surg Clin North Am ; 85(3): 539-53, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15927650

ABSTRACT

The incidence of esophageal adenocarcinoma is rising in the United States and Western countries. Significant differences exist between esophageal adenocarcinoma and squamous cell carcinoma in the molecular mechanisms responsible for the tumorigenesis process. State-of-the-art techniques such as gene microarrays and proteomics will greatly aid in the development of new therapies targeting specific molecular pathways,ultimately leading to improved survival in patients who have esophageal cancer.


Subject(s)
Adenocarcinoma/genetics , Esophageal Neoplasms/genetics , Genomics/methods , Molecular Biology/methods , Apoptosis/genetics , Esophageal Neoplasms/epidemiology , Gene Expression/genetics , Genes, Tumor Suppressor , Humans , Oligonucleotide Array Sequence Analysis , Proteomics/methods , Vascular Endothelial Growth Factor A/genetics
16.
J Thorac Cardiovasc Surg ; 129(6): 1250-7, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15942564

ABSTRACT

OBJECTIVE: We sought to study the clinical characteristics and outcomes of patients treated with a surgery-inclusive multimodality approach for Pancoast tumors. METHODS: Clinical records of patients with Pancoast lung cancer who were enrolled for multimodality treatment between 1993 and 2003 at our institution were reviewed retrospectively. RESULTS: Thirty-six patients completed neodjuvant chemoradiation followed by en bloc surgical resection, whereas one patient received high-dose radiation alone followed by surgical intervention. There were 22 men and 15 women. Thirty-four lobectomies and 3 pneumonectomies were performed. Pretreatment non-small cell lung cancer stages were IIB, IIIA, IIIB, and IV (presenting with solitary brain metastasis) in 18, 8, 6, and 5 cases, respectively. R0 resection was achieved in 36 (97.3%) patients. Operative mortality was 2.7% (n = 1). High-dose radiotherapy was successfully tolerated in all but 1 patient. Mean total radiation dose was 56.9 Gy. Pathologic complete response was found in 40.5% (n = 15) of patients. Recurrences were found in 50% (n = 18) of patients. Brain metastasis was the most common recurrence (n = 9), followed by other distant recurrences (n = 4) and local recurrences (n = 5). Median survival time for the group is 2.6 years, and median survival time (pathologic complete response) is 7.8 years. It is noteworthy that median survival time of patients with positive pretreatment lymph nodes (12 patients) was not reached. CONCLUSIONS: Surgical resection of Pancoast tumors after neoadjuvant high-dose radiation and chemotherapy can be safely performed. High-dose radiation in trimodality treatment is well tolerated and might be beneficial. Similar to other studies, late central nervous system relapse is problematic and indicates a need for assessing the role of prophylactic cranial irradiation in this disease.


Subject(s)
Pancoast Syndrome/mortality , Pancoast Syndrome/radiotherapy , Adult , Aged , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Pancoast Syndrome/drug therapy , Pancoast Syndrome/surgery , Radiotherapy Dosage , Remission Induction , Retrospective Studies , Survival Rate , Time Factors
17.
Ann Thorac Surg ; 76(4): 996-9; discussion 999-1000, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14529974

ABSTRACT

BACKGROUND: With recent advances in neoadjuvant therapy in esophageal cancer, pretreatment lymph node staging has become increasingly important in stratifying patients to appropriate treatment regimens and for prognostication. Immunohistochemical analysis (IHC) using epithelial markers has been shown to identify micrometastases in histologically negative lymph nodes. We performed this study to evaluate if IHC analysis in thoracoscopic/laparoscopic (Ts/Ls) pretreatment staging lymph nodes can reveal additional diagnostic information to routine histopathology. METHODS: Specimens of 106 patients with esophageal cancer who had pretreatment Ts/Ls staging were retrospectively studied. Lymph node biopsies were obtained for IHC staining using cytokeratin (CK) of AE1/AE3. IHC staining for p53, an apoptosis protein associated with poor prognosis in esophageal cancer, was also performed. RESULTS: 331 Ts/Ls staging lymph node biopsies were collected from 106 patients. A total of 15.4% (51/331) of the lymph nodes or 34.9% (37/106) of patients were found to have metastatic deposits by routine histology. All the histologically positive lymph nodes were CK positive. Among the remaining 280 histologically negative lymph nodes, 11(3.9%) were found to have micrometastasis by CK staining. Three patients (4.3%, 3/69) were upstaged from N0 to N1. They died of early recurrences after treatment. A total of 67.6% (25/37) of the patients with histologically positive lymph node were p53 positive. No histologically negative lymph node was found to be p53 positive in this series. CONCLUSIONS: Immunohistochemical analysis for CK can detect micrometastatic involvement of lymph nodes that are missed on routine pathologic examination, and, therefore, can improve lymph node staging. Its clinical significance in esophageal cancer warrants further study.


Subject(s)
Esophageal Neoplasms/pathology , Keratins/analysis , Lymphatic Metastasis/diagnosis , Tumor Suppressor Protein p53/analysis , Aged , Aged, 80 and over , Biopsy , Humans , Immunohistochemistry , Lymphatic Metastasis/pathology , Male , Middle Aged , Neoplasm Staging , Prognosis , Retrospective Studies
18.
Surg Laparosc Endosc Percutan Tech ; 12(4): 213-8, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12193812

ABSTRACT

Precise clinical staging of esophageal cancer before treatment is important. Thoracoscopic/laparoscopic (Ts/Ls) staging has been proposed as a promising staging method. This study was conducted to evaluate the potential benefits of Ts/Ls staging over conventional noninvasive clinical staging in patients with esophageal cancer. From 1991 to 1999, 111 patients with esophageal cancer underwent Ts/Ls staging by the University of Maryland Medical System. Pretreatment staging workup included computed tomography, magnetic resonance imaging, and esophageal ultrasonography, followed by Ts/Ls surgical staging. Thoracoscopy was successfully performed in 102 patients and was aborted in 4 patients because of pleural adhesions. Laparoscopy was successfully done in 76 patients and was aborted in 1 patient because of peritoneal adhesion. Sixty-seven patients had both Ts and Ls staging, whereas 35 patients and 9 patients, respectively, had only Ts or Ls staging. Thirteen of 19 patients with clinical T4 disease were downstaged to T3 disease, and 8 patients with clinical T3 disease were upstaged to T4 by Ts/Ls staging. No clinical T1-2 disease was found to be associated with local invasion (T4) by Ts/Ls. Forty-eight and 19 patients had mediastinal and celiac lymph node metastases clinically diagnosed, respectively. Nine (18.8%) and 12 (63.2%) of them were proved by Ts and Ls, respectively. An additional 5 and 16 patients were found to have unexpected mediastinal and celiac lymph node metastases, respectively, by Ts/Ls. Biopsy specimens of pleura, lung, or liver were obtained by Ts/Ls procedures in 17 patients because of suspicious findings of routine imaging studies or unexpected findings during the staging operation. Five patients were found to have distant metastasis, and the presence of metastases in others was excluded. The correlation between Ts/Ls staging and conventional noninvasive clinical staging in the diagnosis of T4 disease, mediastinal lymph node metastasis, celiac lymph node metastasis, and M1 disease was 18.8%, 14.5%, 25.5%, and 20.0%, respectively. Ts/Ls provides more accurate information for evaluating local invasion, lymph node metastasis, and distant metastasis. The poor correlation of staging diagnosis between Ts/Ls and conventional noninvasive clinical examinations suggests that the accuracy of current noninvasive clinical staging is questionable and needs to be improved.


Subject(s)
Adenocarcinoma/pathology , Carcinoma, Squamous Cell/pathology , Esophageal Neoplasms/pathology , Laparoscopy , Neoplasm Staging/methods , Thoracoscopy , Adenocarcinoma/surgery , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/surgery , Esophageal Neoplasms/surgery , Female , Humans , Male , Maryland , Middle Aged , Predictive Value of Tests , Retrospective Studies , Sensitivity and Specificity
19.
Heart Surg Forum ; 5(2): 105-8, 2002.
Article in English | MEDLINE | ID: mdl-12114122

ABSTRACT

BACKGROUND: Cardiac surgery is perceived to be maximally invasive and fraught with complications. In response to this perception, cardiothoracic surgeons have been refining traditional techniques to minimize their invasive nature. Epidural anesthesia has been used safely and effectively for numerous surgical procedures to reduce morbidity associated with general anesthesia. In hopes of achieving a similar result, we set out to determine the feasibility of using thoracic epidural anesthesia for limited cardiac surgery through a left anterior thoracotomy for patients who were awake and spontaneously breathing. METHODS: A high thoracic epidural technique was used in all cases. In each instance, the chest was entered through a small left anterior thoracotomy. The procedures included minimally invasive direct coronary artery bypass (MIDCAB) and transmyocardial revascularization (TMR). These procedures were performed in routine fashion using standard techniques. Pulmonary function tests were performed preoperatively, and the adequacy of respiratory function was serially monitored throughout each operation. The epidural catheters were left in place for 24 hours after operation for pain control. RESULTS: A total of 10 operations were performed. These included 7 MIDCAB, 2 TMR and 1 MIDCAB/TMR hybrid. The mean preoperative forced expiratory volume for one second (FEV1) was 1.9 liters. Significant intra-operative hypoxia or hypercarbia was not seen. One patient required intubation during the procedure for restlessness not associated with hypoxia. Two others required brief periods of assisted ventilation. All procedures were completed without incident. The mean operating time and length of stay were 70 minutes and 4.7 days. Postoperative pain control and patient satisfaction were excellent. CONCLUSIONS: Thoracic epidural anesthesia for limited cardiac surgical procedures by means of a left anterior thoracotomy is feasible, even in patients with diminished pulmonary function. Furthermore, this method offered no significant technical hurdles. Nevertheless, the applicability of this technique to other procedures remains unclear. We believe that these results warrant controlled comparison of regional versus general anesthesia for limited cardiac surgery.


Subject(s)
Anesthesia, Epidural/methods , Cardiac Surgical Procedures , Thoracotomy , Aged , Feasibility Studies , Humans , Male , Middle Aged , Treatment Outcome
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