Analysis of trimodal and bimodal therapy in a selective-surgery paradigm for locally advanced oesophageal squamous cell carcinoma.

BACKGROUND: Long-term survival outcomes of trimodal therapy (TMT; chemoradiation plus surgery) and bimodal therapy (BMT; chemoradiation) have seldom been analysed. In a selective-surgery paradigm, the benefit of TMT in patients with a complete clinical response is controversial. Factors associated with survival in patients with a clinical complete response to chemoradiation were evaluated. METHODS: Patients with stage II-III oesophageal squamous cell carcinoma treated with TMT or BMT from 2002 to 2017 were evaluated. The BMT group consisted of patients who were otherwise eligible for surgery but underwent chemoradiation alone followed by observation. This group included patients who later had salvage oesophagectomy. Survival was evaluated and compared between TMT and BMT groups. Elastic net regularization was performed to select co-variables for Cox multivariable survival analysis in patients with a clinical complete response. RESULTS: Of 143 patients, 60 (41.9 per cent) underwent TMT and 83 (58.0 per cent) BMT. Patients who underwent TMT had longer median overall survival than those who had BMT (77 versus 33 months; P = 0.019). For patients with a clinical complete response, TMT achieved longer median overall survival than BMT (123 versus 55 months; P = 0.04). BMT had a high locoregional recurrence rate (48 versus 6 per cent; P < 0.001); 26 of 29 patients with locoregional recurrence in the BMT groupunderwent salvage resection. Cox multivariable analysis demonstrated that upper-mid oesophageal tumour location (hazard ratio (HR) 2.04; P = 0.024) and tumour length (HR 1.18; P = 0.046) were associated with worse survival. Although TMT was not associated with survival, it was a predictor of reduced recurrence (HR 0.28; P = 0.028). The maximum standardized uptake value after chemoradiation also predicted recurrence (HR 1.33; P < 0.001). CONCLUSION: In patients who achieve a clinical complete response, TMT reduces locoregional recurrence but may not prolong survival. The differences in survival outcomes may be due to patient selection; therefore, a selective-surgery strategy in oesophageal squamous cell carcinoma is a reasonable approach.

Morbidity following salvage esophagectomy for squamous cell carcinoma: the MD Anderson experience.

The survival advantage associated with the addition of surgical therapy in esophageal squamous cell carcinoma (ESCC) patients who demonstrate a complete clinical response to chemoradiotherapy is unclear, and many institutions have adopted an organ-preserving strategy of selective surgery in this population. We sought to characterize our institutional experience of salvage esophagectomy (for failure of definitive bimodality therapy) and planned esophagectomy (as a component of trimodality therapy) by retrospectively analyzing patients with ESCC of the thoracic esophagus and GEJ who underwent esophagectomy following chemoradiotherapy between 2004 and 2016. Of 76 patients who met inclusion criteria, 46.1% (35) underwent salvage esophagectomy. Major postoperative complications (major cardiovascular and pulmonary events, anastomotic leak [grade ≥ 2], and 90-day mortality) were frequent and occurred in 52.6% of the cohort (planned resection: 36.6% [15/41]; salvage esophagectomy: 71.4% [25/35]). Observed rates of 30- and 90-day mortality for the entire cohort were 7.9% (planned: 7.3% [3/41]; salvage: 8.6% [3/35]) and 13.2% (planned: 9.8% [4/41]; salvage: 17.1% [6/35]), respectively. In summary, esophagectomy following chemoradiotherapy for ESCC at our institution has been associated with frequent postoperative morbidity and considerable rates of mortality in both planned and salvage settings. Although a selective approach to surgery may permit organ preservation in many patients with ESCC, these results highlight that salvage esophagectomy for failure of definitive-intent treatment of ESCC may also constitute a difficult clinical undertaking in some cases.

Gender-based analysis of esophageal cancer patients undergoing preoperative chemoradiation: differences in presentation and therapy outcome.

The purpose of this study was to identify gender-dependent differences in presentation at baseline and therapy outcome in esophageal carcinoma patients treated with preoperative chemoradiotherapy (CTRT). We stratified patients according to gender and statistically compared pretreatment clinical stage, post-CTRT effect on carcinoma in the resected specimen, overall survival (OS), and patterns of failure. Of the 235 patients who underwent preoperative CTRT, 203 were men and 32 were women. Carcinomas in women correlated significantly with clinical stage II classification (78%vs. 55%) while cancers in men correlated significantly with clinical stage III classification (39%vs. 16%; P = 0.02). Carcinomas in women also correlated significantly with lower clinical N classification; more women had cN0 (52%) compared to men (28%; P = 0.01). Similarly, in the surgical specimens, more women had pN0 (78%) compared to men (64%; P = 0.06). At a median follow-up of 37 months, 10% more women than men remain alive (63%vs. 53%; P = 0.3). Distant metastases-free survival time was longer for women than men. Our results suggest that localized esophageal carcinoma is diagnosed in more advanced stages in men than in women. The reasons for these differences remain unclear and further expansion of these observations and study of biologic differences that might exist are warranted.

Open lung biopsy in bone marrow transplant recipients has a poor diagnostic yield for a specific diagnosis.

The diagnostic yield of open lung biopsy (OLB) in bone marrow transplantation (BMT) recipients having pulmonary infiltrates has not been evaluated recently. Therefore, we reviewed our 2-year experience (1998-99) with such patients at The University of Texas M. D. Anderson Cancer Center. We found 12 BMT recipients who underwent OLB analysis for the evaluation of pulmonary infiltrates. A treatable infectious etiology leading to the initiation or modification of antimicrobial agent administration was found in only two patients having bilateral nodular disease and one having bilateral parenchymal infiltrates. We conclude that OLB in BMT patients having diffuse pulmonary infiltrates has a low diagnostic yield for treatable infectious etiologies.

Activation of melanoma antigen tumor antigens occurs early in lung carcinogenesis.

The melanoma antigen (MAGE)-encoding genes are expressed in various tumor types, including lung, and are thought to be silent in all normal tissues except testis. In search of biomarkers for early lung cancer detection and cancer risk assessment, we investigated frequencies of expressional activation of MAGE-A1, -A3, and -B2 genes in non-small cell lung cancers (NSCLCs). Expression of these genes was evaluated by reverse transcription-PCR (RT-PCR) in 20 primary NSCLC samples and corresponding normal lung tissues as well as in 20 bronchial brush specimens from former smokers without lung cancer. mRNA in situ hybridization was done to confirm the gene expression pattern at the cellular level. Methylation-specific PCR was performed to evaluate the hypomethylation status of CpG sites in the promoter regions of these genes. Among the 20 primary NSCLC samples analyzed, 14 (70%) expressed MAGE-A1 and 17 (85%) each expressed MAGE-A3 and MAGE-B2. A substantial number of normal lung tissues adjacent to NSCLC also had a detectable level of MAGE expression (65, 75, and 80% for MAGE-A1, -A3, and -B2, respectively). We found that 7 (35%), 10 (50%), and 11 (55%) of the adjacent normal lung tissue samples exhibited promoter hypomethylation at MAGE-A1, -A3, and -B2, respectively, compared with 15 (75%), 16 (80%), and 16 (80%) of the NSCLC samples. Among the 20 bronchial epithelium samples from former smokers, 7 (35%), 10 (50%), and 12 (60%) had also detectable -A1, -A3, and -B2 expression, respectively. Activation of MAGE-A1, -A3, and -B2 genes is common not only in NSCLC but also in bronchial epithelium with severe carcinogen insult. These results suggest that MAGE genes may be activated very early in lung carcinogenesis and may be considered as targets for lung cancer prevention.

Preoperative chemotherapy for lung cancer does not increase surgical morbidity.

BACKGROUND: Preoperative chemotherapy (C+S) for non-small cell lung cancer (NSCLC) has increased in an attempt to improve survival. Patients receiving C+S potentially may have an increase in postoperative morbidity and mortality compared with surgery alone (S). We reviewed our experience with C+S and S in a tertiary referral center. METHODS: Three hundred eighty consecutive patients underwent lobectomy or greater resection for NSCLC between August 1, 1996, and April 30, 1999: 335 patients (259 S; 76 C+S) were analyzed; 45 additional patients were excluded for prior NSCLC, other chemotherapy for other malignancy, or radiation. We compared morbidity and mortality overall, and by subset analysis (clinical stage, pathological stage, procedure, and by protocol use) for both C+S and S patients. RESULTS: Demographics, comorbidities, and spirometry were similar. We noted no significant difference in overall or subset mortality or morbidity including pneumonia, acute respiratory distress syndrome, reintubation, tracheostomy, wound complications, or length of hospitalization. CONCLUSIONS: C+S did not significantly affect morbidity or mortality overall, based on clinical stage, postoperative stage, or extent of resection. The potential for enhanced survival in resectable NSCLC justifies continued study of C+S.

Simultaneous anterior-posterior approach to the thoracic and lumbar spine for the radical resection of tumors followed by reconstruction and stabilization.

OBJECT: Thoracic or lumbar spine malignant tumors involving both the anterior and posterior columns represent a complex surgical problem. The authors review the results of treating patients with these lesions in whom surgery was performed via a simultaneous anterior-posterior approach. METHODS: The hospital records of 26 patients who underwent surgery via simultaneous combined approach for thoracic and lumbar spinal tumors at our institution from July 1994 to March 2000 were reviewed. Surgery was performed with the patients in the lateral decubitus position for the procedure. The technical details are reported. The mean survival determined by Kaplan-Meier analysis was 43.4 months for the 15 patients with primary malignant tumors and 22.5 months for the 11 patients with metastatic spinal disease. At 1 month after surgery, 23 (96%) of 24 patients who complained of pain preoperatively reported improvements (p < 0.001, Wilcoxon signed-rank test), and eight (62%) of 13 patients with preoperative neurological deficits were functionally improved (p = 0.01). There were nine major complications, five minor complications, and no deaths within 30 days of surgery. Two patients (8%) later underwent surgery for recurrent tumor. CONCLUSIONS: The simultaneous anterior-posterior approach is a safe and feasible alternative for the exposure tumors of the thoracic and lumbar spine that involve both the anterior and posterior columns. Advantages of the approach include direct visualization of adjacent neurovascular structures, the ability to achieve complete resection of lesions involving all three columns simultaneously (optimizing hemostasis), and the ability to perform excellent dorsal and ventral stabilization in one operative session.

Surgical resection of non-small cell carcinoma after treatment for small cell carcinoma.

BACKGROUND: Development of non-small cell lung carcinoma (NSCLC) in patients previously treated for small cell carcinoma (SCLC/NSCLC) is well described; however, little is known about clinical outcome. METHODS: A single-institution 20-year review was performed. Patient characteristics and survival for SCLC/ NSCLC patients were compared with those for control patients matched for stage, resection, and previous malignancy. RESULTS: One thousand four hundred four patients with small cell carcinoma were identified, and 29 underwent therapy for metachronous NSCLC: 11 of 29 patients underwent surgical resection, 10 of these 11 (90%) were stage I. Compared with surgically treated stage I NSCLC patients, SCLC/NSCLC patients were more likely to have squamous histology (70% versus 35%, p = 0.026); and subanatomic resection (90% versus 17.4%, p < 0.0005). The SCLC/NSCLC patients had significantly poorer survival when compared with stage I NSCLC patients undergoing any resection (24.53 versus 74.43 months, p = 0.003) and stage I NSCLC patients receiving wedge resection (24.53 versus 58.39 months, p = 0.006). Survival was similar to NSCLC patients with a history of previous treated extrathoracic solid malignancy. CONCLUSIONS: Surgical resection for SCLC/NSCLC patients is feasible, but poorer prognosis is noted when compared with stage-matched control patients. Surgical candidates should be carefully chosen, and alternative local control modalities considered.

Treatment of stage I lung cancer.

This article reviews changes in the roles of surgeons, medical oncologists, and radiation oncologists that have occurred over the past 20 years. A gradual evolution will certainly continue over the next several decades in the multidisciplinary quest to improve the dismal survival results.

A single-institutional, multidisciplinary approach to primary sarcomas involving the chest wall requiring full-thickness resections.

OBJECTIVE: Primary sarcomas involving the chest wall requiring full-thickness excision are rare. We reviewed our experience with these lesions in a tertiary referral cancer center by using multidisciplinary approaches. METHODS: A 10-year retrospective study identified 51 patients referred with primary sarcomas of the chest wall: 40 for initial treatment and 11 after previous unsuccessful surgical excisions elsewhere (secondary referral). Presenting symptoms were pain alone in 23 (45%) of 51 patients, pain with an associated mass in 8 (16%) patients, and an asymptomatic mass alone in 13 (25%) patients. Median symptom duration was 241 days in the primary group and 225 days in the recurrent group. Tumor locations were the sternum (n = 11), the rib alone (n = 36), and the posterior rib with extension into vertebral bodies (n = 4). Histologic types included the following: chondrosarcomas (n = 15), malignant fibrous histiocytomas (n = 9), osteosarcomas (n = 4), Ewing sarcomas (n = 3), desmoid tumors (n = 7), and other types (n = 13). The median tumor volume of those referred initially was 311 cm(3) compared with 84 cm(3) in patients with recurrent lesions. RESULTS: Twenty-six (51%) of 51 patients received treatment before resection, including chemotherapy alone (n = 22), radiation alone (n = 3), and combined chemotherapy and radiation therapy (n = 1). The complete sternum was removed in 6 of 11 patients, and the average number of ribs requiring resection was 3.8. Four patients had vertebral body resections. Prosthetic meshes alone were required in 16 of 51 patients, and meshes with methylmethacrylate were required in 18 of 51 patients. Muscle flap reconstructions by plastic surgery were required in 24 patients. Negative margins were obtained in 47 of 51 patients. There were no perioperative deaths with morbidities occurring in 12 (24%) of 51 patients (wound [n = 3], prolonged air leak [n = 1], prolonged ventilator requirement [n = 1], arrhythmias [n = 3], doxorubicin (Adriamycin)-induced cardiomyopathy [n = 1], and other [n = 3]). Postoperative treatment was administered to 13 patients (chemotherapy alone, n = 9; chemotherapy with radiation therapy, n = 4). The cumulative 5-year survival of all patients was 64% (initial referral, 61.3%; secondary referral, 72.7%). The average follow-up is 44.7 months. CONCLUSIONS: A combined aggressive multidisciplinary approach to primary sarcomas of the chest wall resulted in no treatment-related deaths and a cumulative 5-year survival of 64% in patients referred to our tertiary care cancer center.

Outcome predictors for 143 patients with superior sulcus tumors treated by multidisciplinary approach at the University of Texas M. D. Anderson Cancer Center.

PURPOSE: Superior sulcus tumors (SST) of the lung are uncommon and constitute approximately 3% of non-small cell lung cancer (NSCLC). These tumors cause specific symptoms and signs, and are associated with patterns of failure that differ from those seen for NSCLC tumors in other nonapical locations. Prognostic factors and most effective treatments are controversial. We conducted a retrospective study at The University of Texas M. D. Anderson Cancer Center to identify outcome predictors for patients with SST treated by a multidisciplinary approach. METHODS AND MATERIALS: This retrospective review of 143 patients without distant metastasis at presentation is a continuation of a previous M. D. Anderson study now updated to 1994. In this study, we examine the 5-year survival rate by pretreatment tumor and patient characteristics and by the treatments received. Strict criteria were used to define SST. Actuarial life-table analyses and Cox proportional hazard models were used to compare survival rates. RESULTS: Overall predictors of 5-year survival were weight loss (p < 0.01), supraclavicular fossa (p = 0. 03), or vertebral body (p = 0.05) involvement, stage of the disease (p < 0.01), and surgical treatment (p < 0.01). Five-year survival for patients with Stage IIB disease was 47% compared to 14% for Stage IIIA, and 16% for Stage IIIB. For patients with Stage IIB disease, surgical treatment (p < 0.01) and weight loss (p = 0.01) were significant independent predictors of 5-year survival. Among patients with Stage IIIA disease, the only predictor of survival was Karnofsky performance score (KPS) (p = 0.02). For patients with Stage IIIB disease, the only independent predictor of survival was a right superior sulcus location, which was associated with a worse 5-year survival rate than that for patients with tumors in the left superior sulcus (p = 0.02). More patients with adenocarcinoma than with squamous cell tumors experienced cerebral metastases within 5 years (p < 0.01). Patients without gross residual disease after surgical resection who received postoperative radiation therapy with total doses of 55 to 64 Gy had a 5-year survival rate of 82% as compared with the 5-year survival rate of 56% in patients who received 50 to 54 Gy. Twenty-three patients survived for longer than 3 years. Of these, 4 patients (17%) received radiation therapy alone or in combination with chemotherapy without surgical resection. The other 19 patients (83%) had resection combined with radiation therapy and/or chemotherapy. CONCLUSIONS: The findings from this study confirm the importance of the new staging system, separating T3 N0 M0 (Stage IIB) from Stage IIIA, since there was a significant difference in the 5-year survival (p < 0.01). Interestingly, there was no significant 5-year survival difference between Stage IIIA (N2) and Stage IIIB (T4 or N3). This study also suggests that surgery is an important component of the multidisciplinary approach to patients with SST if their nodes were negative. Disease that is minimally invading surrounding normal structures can be resected followed by radiation therapy in doses of 55 to 64 Gy. Further investigation of treatment strategies combining high-dose radiation therapy (>/=66 Gy) with chemotherapy is indicated for patients with unresectable and/or node-positive (N2) SST.

Insulin-like growth factor binding protein-6 inhibits the growth of human bronchial epithelial cells and increases in abundance with all-trans-retinoic acid treatment.

Retinoids are potent inhibitors of human bronchial epithelial (HBE) cell growth. Retinoids initiate signaling through activation of nuclear receptors, but the signal transduction pathways that mediate growth inhibition have not been defined. In this study, we investigated the expression of insulin-like growth factor (IGF)-binding protein (IGFBP)-6 as a potential mediator of retinoid actions. IGFBP-6 is a secreted glycoprotein that inhibits the bioavailability of IGFs, which are potent mitogens of HBE cells. IGFBP-6 was detected by immunohistochemical staining in the basal epithelial layer of human bronchial organ cultures, and all-trans-retinoic acid (t-RA) treatment increased the intensity of IGFBP-6 immunostaining. In primary cultures of HBE cells treated with t-RA, IGFBP-6 messenger RNA and protein levels increased within 6 and 24 h, respectively, and IGFBP-6 was detected in the conditioned media at 48 h. The effect of IGFBP-6 on HBE cell growth was investigated with a recombinant adenoviral vector, Ad5CMV-BP6, which expresses IGFBP-6 under the control of a cytomegalovirus promoter. IGFBP-6 overexpression induced a proliferative arrest of HBE cells with no evidence of apoptosis. These findings provide the first evidence that IGFBP-6 is expressed in the bronchial epithelium and that IGFBP-6 may contribute to the biologic effects of retinoids on HBE cells.

N-(4-hydroxyphenyl)retinamide in the chemoprevention of squamous metaplasia and dysplasia of the bronchial epithelium.

Lung cancer remains the number one cause of cancer-related deaths in the United States. To reduce the mortality associated with this disease, individuals at risk must be identified prior to the development of lung cancer, and effective prevention strategies must be developed. One such strategy is to use retinoids like N-(4-hydroxyphenyl)retinamide (4-HPR), which has been found to possess chemopreventive activities in preclinical studies. In this study, 139 smokers were registered and 82 were randomized onto a double-blinded, placebo-controlled chemoprevention trial of 4-HPR administered p.o. (200 mg once daily). Of these, 70 participants were eligible for response evaluation. Biopsies were obtained at six predetermined sites in the bronchial tree from participants before and at the completion of 6 months of treatment. 4-HPR treatment had no measurable effect on histopathology (squamous metaplasia and dysplasia) in the bronchial epithelium of current smokers. 4-HPR was detected (104.5+/-64.0 ng/ml, mean +/- SD) in the serum of participants, supporting its potential bioavailability. Serum retinol levels decreased markedly (44% of placebo-treated patients) as a consequence of 4-HPR treatment. Notably, the mRNA level of retinoic acid receptor beta, which is typically increased by retinoid treatment, did not change in the bronchial epithelium of 4-HPR-treated participants. Clonal populations of bronchial epithelial cells were detected by analysis of loss of heterozygosity at putative tumor suppressor loci on chromosomes 3p, 9p, and 17p, and these changes were not altered by 4-HPR treatment. In conclusion, at this dose and schedule, 4-HPR was not effective in reversing squamous metaplasia, dysplasia, or genetic and phenotypic abnormalities in the bronchial epithelium of smokers.

C-CAM1, a candidate tumor suppressor gene, is abnormally expressed in primary lung cancers.

Previous studies have shown that the expression of the cell-cell adhesion molecule (C-CAM1), located at chromosome 19, is down-regulated in several types of human cancers, including prostate and breast cancers. Two major isoforms of C-CAM1, the long or L-form C-CAM1 and the short or S-form C-CAM1, are derived from the C-CAM1 gene through alternative splicing. Tumor cells transfected with L-form C-CAM1, which contains a cytoplasmic domain, display significantly lower growth rates and less tumorigenicity in both in vitro and in vivo models compared with untransfected tumor cells, suggesting that L-form C-CAM1 may be a tumor suppressor. The transfection of the cytoplasmic domain of L-form C-CAM1 could also cause suppression of tumor growth, further supporting the role of L-form C-CAM1 in tumorigenesis. In contrast to reports of most of the tumor types tested, Ohwada et al. (Am. J. Respir. Cell Mol. Biol., 11: 214-220, 1994) reported that C-CAM1 was not down-regulated or even up-regulated in lung cancer. Because the cytoplasmic domain of L-form C-CAM1 is critical for the tumor suppressor function of C-CAM1, we hypothesized that switching of the isoform rather than down- regulation of C-CAM1 gene expression occurs during lung tumorigenesis. To test this hypothesis, we analyzed pairs of tumor tissue and corresponding normal-appearing lung tissue from 51 patients with non-small cell lung cancer (NSCLC) and 43 cell lines to determine expression profiles of L-form C-CAM1 and S-form C-CAM1 using reverse transcription-PCR. We found that L-form C-CAM1 was the predominant form (75%; 38 of 51) in normal-appearing lung tissue, whereas most (84%; 43 of 51) of the primary NSCLC tissue samples expressed predominantly S-form C-CAM1 (P < 0.0001). Similarly, 19 (79%) of the 24 NSCLC cell lines and 17 (85%) of the 20 small cell lung cancer cell lines expressed predominantly S-form C-CAM1. The frequent alteration of the C-CAM1 expression pattern suggests that C-CAM1 has an important role in lung tumorigenesis.

Retinoic acid receptor-beta as a prognostic indicator in stage I non-small-cell lung cancer.

PURPOSE: Retinoids are pivotal in the growth and differentiation of certain epithelial tissues, interacting with nuclear retinoid receptors (the retinoic acid receptors [RARs] and retinoid X receptors [RXRs]), which function as transcription factors. RAR-beta mRNA is undetectable by in situ hybridization (ISH) in 50% of non-small-cell lung cancers (NSCLC). RAR-beta may suppress tumorigenicity. Therefore, we hypothesized that loss of expression of RAR-beta gene in stage I NSCLC is a prognostic factor of a poor clinical outcome. PATIENTS AND METHODS: We retrospectively analyzed RAR-beta mRNA levels (by ISH using a digoxigenin-labeled antisense riboprobe) in specimens from 185 consecutive patients with completely resected clinical/radiographic stage I NSCLC for whom clinical follow-up data were available. RESULTS: One hundred fifty-six patients who met the criteria of pathologic stage I NSCLC and positivity for RXR-alpha mRNA (used as a control to assess RNA degradation) and who had adequate follow-up could be evaluated. RAR-beta mRNA expression was undetectable in 51 patients, weakly positive in 64 patients, and strongly positive in 41 patients. Overall survival of the 41 patients with strongly positive RAR-beta was significantly worse than for the 115 patients with weak or absent RAR-beta (P =.045). CONCLUSION: Unexpectedly, strong RAR-beta expression was associated with a significantly worse outcome of early-stage NSCLC. The mechanisms underlying this clinically and biologically important finding should be further explored.

Phase II study of intravenous Doxil in malignant pleural mesothelioma.

Twenty-four patients with pleural mesothelioma received 50 mg/m2 of Doxil every four weeks. At follow-up, the disease had stabilized in 43% percent of patients and had progressed in 57%. No objective responses were observed. Estimated median survival of all patients was 37 weeks. Major toxicities were erythrodysesthesia of hands and feet and myelosuppression. No cardiac toxicity was observed. We concluded that Doxil at this dosage and schedule is inactive against pleural mesothelioma.

Effect of operative volume on morbidity, mortality, and hospital use after esophagectomy for cancer.

OBJECTIVE: We sought to evaluate the effect of operative volume, hospital size, and cancer specialization on morbidity, mortality, and hospital use after esophagectomy for cancer. METHODS: Data derived from the Health Care Utilization Project was used to evaluate all Medicare-reimbursed esophagectomies for treatment of cancer from 1994 to 1996 in 13 national cancer institutions and 88 community hospitals. The complications of care, length of stay, hospital charges, and mortality were assessed according to hospital size (>/=600 beds vs <600 beds), cancer specialization (national cancer institution vs community hospital), and operative volume (esophageal [>/=5 Medicare esophagectomies per year vs <5 Medicare esophagectomies per year] and nonesophageal operations [>/=3333 cases per year vs <3333 cases per year]). RESULTS: Mortality was lower in national cancer institution hospitals (4.2% [confidence interval, 2.0%-6.4%] vs 13.3% [confidence interval, 4.2%-26.2%], P =. 05) and in hospitals performing a large number of esophagectomies (3. 0% [confidence interval, 0.09%-5.1%] vs 12.2% [confidence interval, 4.5%-19.8%], P <.05). Multivariate analysis revealed that the independent risk factor for operative mortality was the volume of esophagectomies performed (odds ratio, 3.97; P =.03) and not the number of nonesophageal operations, hospital size, or cancer specialization. Hospitals performing a large number of esophagectomies also showed a tendency toward decreased complications (55% vs 68%, P =.06), decreased length of stay (14.7 days vs 17.7 days, P =.006), and decreased charges ($39,867 vs $62, 094, P <.005). CONCLUSIONS: These results demonstrate improved outcomes and decreased hospital use in hospitals that perform a large number of esophagectomies and support the concept of tertiary referral centers for such complex oncologic procedures as esophagectomies.

Cellular and humoral immune responses to adenovirus and p53 protein antigens in patients following intratumoral injection of an adenovirus vector expressing wild-type. P53 (Ad-p53).

The immune responses of 10 patients with advanced non-small cell lung cancer receiving monthly intratumoral injections of a recombinant adenovirus containing human wild-type p53 (Ad-p53) to adenovirus and transgene antigens were studied. The predominate cellular and humoral immune responses as measured by lymphocyte proliferation and neutralizing antibody (Ab) formation were to adenovirus serotype 5 vector antigens, with increased responses in posttreatment samples. Consistent alterations in posttreatment cellular and humoral immune responses to p53 epitopes were not observed, and cytotoxic Abs to human lung cancer cells were not generated. Patients in this study had evidence of an antitumoral effect of this treatment with prolonged tumor stability or regression; however, neither Abs to p53 protein nor increased lymphocyte proliferative responses to wild-type or mutant p53 peptides have been consistently detected.

Coaxial double-lumen methylmethacrylate reconstruction in the anterior cervical and upper thoracic spine after tumor resection.

OBJECT: A unique method of anterior spinal reconstruction after decompressive surgery was used to prevent methylmethacrylate-dural contact in cancer patients who underwent corpectomy. The purpose of this study was to assess the efficacy and stability of polymethylmethacrylate (PMMA) anterior surgical constructs in conjunction with anterior cervical plate stabilization (ACPS) in these patients. METHODS: Approximately 700 patients underwent spinal surgery at The University of Texas M. D. Anderson Cancer Center over a 4-year period. The authors conducted a retrospective outcome study for 29 of these patients who underwent anterior cervical or upper thoracic tumor resections while in the supine position. These patients were all treated using the coaxial, double-lumen, PMMA technique for anterior spinal reconstruction with subsequent ACPS. No postoperative external orthoses were used. Twenty-seven patients (93%) harbored metastatic spinal lesions and two (7%) harbored primary tumors. At 1 month postsurgery, significant improvement was seen in spinal axial pain (p<0.001), radiculopathy (p<0.001), gait (p = 0.008), and Frankel grade (p = 0.002). A total of nine patients (31%) underwent combined anterior-posterior 360 degrees stabilization. Twenty-one patients (72%) experienced no complications. Complications related to instrumentation failure occurred in only two patients (7%). There were no cases in which the patients' status worsened, and there were no neurological complications or infections. The median Kaplan-Meier survival estimate for patients with spinal metastases was 9.5 months. At the end of the study, 13 patients (45%) had died and 16 (55%) were alive. Postoperative magnetic resonance images consistently demonstrated that the dura and PMMA in all patients remained separated. CONCLUSIONS: The anterior, coaxial, double-lumen, PMMA reconstruction technique provides a simple means of spinal cord protection in patients in the supine position while undergoing surgery and offers excellent results in cancer patients who have undergone cervical vertebrectomy.