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The subgroup A through E avian sarcoma and leukosis viruses ASLV(A) through ASLV(E) are a group of highly related alpharetroviruses that have evolved to use very different host protein families as receptors. We have exploited genetic selection strategies to force the replication-competent ASLVs to naturally evolve and acquire mutations to escape the pressure on virus entry and yield a functional replicating virus. In this study, evolutionary pressure was exerted on ASLV(B) virus entry and replication using a secreted for of its Tvb receptor. As expected, mutations in the ASLV(B) surface glycoprotein hypervariable regions were selected that knocked out the ability for the mutant glycoprotein to bind the sTvb S3 -IgG inhibitor. However, the subgroup B Rous associated virus 2 (RAV-2) also required additional mutations in the C-terminal end of the SU glycoprotein and multiple regions of TM highlighting the importance of the entire viral envelope glycoprotein trimer structure to mediate the entry process efficiently. These mutations altered the normal two-step ASLV membrane fusion process to enable infection.

Background: A robust bacterial artificial chromosome (BAC)-based physical map is essential for many aspects of genomics research, including an understanding of chromosome evolution, high-resolution genome mapping, marker-assisted breeding, positional cloning of genes, and quantitative trait analysis. To facilitate turkey genetics research and better understand avian genome evolution, a BAC-based integrated physical, genetic, and comparative map was developed for this important agricultural species., Results: The turkey genome physical map was constructed based on 74,013 BAC fingerprints (11.9 × coverage) from two independent libraries, and it was integrated with the turkey genetic map and chicken genome sequence using over 41,400 BAC assignments identified by 3,499 overgo hybridization probes along with > 43,000 BAC end sequences. The physical-comparative map consists of 74 BAC contigs, with an average contig size of 13.6 Mb. All but four of the turkey chromosomes were spanned on this map by three or fewer contigs, with 14 chromosomes spanned by a single contig and nine chromosomes spanned by two contigs. This map predicts 20 to 27 major rearrangements distinguishing turkey and chicken chromosomes, despite up to 40 million years of separate evolution between the two species. These data elucidate the chromosomal evolutionary pattern within the Phasianidae that led to the modern turkey and chicken karyotypes. The predominant rearrangement mode involves intra-chromosomal inversions, and there is a clear bias for these to result in centromere locations at or near telomeres in turkey chromosomes, in comparison to interstitial centromeres in the orthologous chicken chromosomes., Conclusion: The BAC-based turkey-chicken comparative map provides novel insights into the evolution of avian genomes, a framework for assembly of turkey whole genome shotgun sequencing data, and tools for enhanced genetic improvement of these important agricultural and model species.

A synergistic combination of two next-generation sequencing platforms with a detailed comparative BAC physical contig map provided a cost-effective assembly of the genome sequence of the domestic turkey (Meleagris gallopavo). Heterozygosity of the sequenced source genome allowed discovery of more than 600,000 high quality single nucleotide variants. Despite this heterozygosity, the current genome assembly (∼1.1 Gb) includes 917 Mb of sequence assigned to specific turkey chromosomes. Annotation identified nearly 16,000 genes, with 15,093 recognized as protein coding and 611 as non-coding RNA genes. Comparative analysis of the turkey, chicken, and zebra finch genomes, and comparing avian to mammalian species, supports the characteristic stability of avian genomes and identifies genes unique to the avian lineage. Clear differences are seen in number and variety of genes of the avian immune system where expansions and novel genes are less frequent than examples of gene loss. The turkey genome sequence provides resources to further understand the evolution of vertebrate genomes and genetic variation underlying economically important quantitative traits in poultry. This integrated approach may be a model for providing both gene and chromosome level assemblies of other species with agricultural, ecological, and evolutionary interest., Competing Interests: The authors have declared that no competing interests exist.

The process of RNA interference (RNAi) has been exploited in cultured chicken cells and in chick embryos to assess the effect of specific gene inhibition on phenotypes related to development and disease. We previously demonstrated that avian leukosis virus-based retroviral vectors are capable of delivering effective RNAi against Marek's disease virus (MDV) in cell culture. In this study, similar RNAi vectors are shown to reduce the replication of MDV in live chickens. Retroviral vectors were introduced into d 0 chick embryos, followed by incubation until hatching. Chicks were challenged with 500 pfu of strain 648A MDV at day of hatch, followed by assays for viremia at 14 d postinfection. Birds were monitored for signs of Marek's disease for 8 wk. A stem-loop PCR assay was developed to measure siRNA expression levels in birds. Delivery of RNAi co-targeting the MDV gB glycoprotein gene and ICP4 transcriptional regulatory gene significantly reduced MDV viremia in vivo, although to lesser extents than were observed in cell culture. Concomitant reductions in disease incidence also were observed, and the extent of this effect depended on the potency of the MDV challenge virus inoculum. Successful modification of phenotypic traits in live birds with retroviral RNAi vectors opens up the possibility that such approaches could be used to alter the expression of candidate genes hypothesized to influence a variety of quantitative traits including disease susceptibility.

RNA interference (RNAi) is a promising antiviral methodology. We recently demonstrated that retroviral vectors expressing short-hairpin RNAs (shRNA-mirs) in the context of a modified endogenous micro-RNA (miRNA) can be effective in reducing replication of other retroviruses in chicken cells. In this study, similar RNAi vectors are shown to inhibit replication of the avian herpesvirus, Marek's disease virus (MDV, also known as gallid herpesvirus type 2), and its close relative, herpesvirus of turkeys (HVT). Cells expressing shRNA-mirs targeting the MDV or HVT gB glycoprotein gene or the ICP4 transcriptional regulatory gene show significant inhibition of viral replication. Not only are viral titers reduced, but observed plaque sizes are significantly smaller when the virus is grown on cells in which RNAi is effective. We also describe a modified retroviral delivery vector that expresses a shRNA-mir containing up to three RNAi target sequences and employ this vector with multiple targets within the MDV gB gene or within both the gB and ICP4 genes. The use of targets within multiple genes potentially can provide a larger antiviral effect and/or make it more difficult for viral escape mutations to evolve.

RNA interference (RNAi) has recently emerged as a promising antiviral technique in vertebrates. Although most studies have used exogenous short interfering RNAs (siRNAs) to inhibit viral replication, vectors expressing short hairpin RNAs (shRNA-mirs) in the context of a modified endogenous micro-RNA (miRNA) are more efficient and are practical for in vivo delivery. In this study, replication competent retroviral vectors were designed to deliver shRNA-mirs targeting subgroup B avian leukosis virus (ALV), the most effective of which reduced expression of protein targets by as much as 90% in cultured avian cells. Cells expressing shRNA-mirs targeting the tvb receptor sequence or the viral env(B) sequence significantly inhibited ALV(B) replication. This study demonstrates efficient antiviral RNAi in avian cells using shRNA-mirs expressed from pol II promoters, including an inducible promoter, allowing for the regulation of the antiviral effect by doxycycline.

This study examined telomerase activity and gene expression profiles for three genes in Gallus gallus domesticus: telomerase reverse transcriptase (chTERT), telomerase RNA (chTR), and c-myc. Expression of these genes was studied in chicken embryonic stem (chES) cells, chicken embryo fibroblasts (CEFs), and DT40 cells using quantitative real-time polymerase chain reaction. Our results establish that, relative to transcription levels in telomerase-negative CEFs, chTERT and chTR are up-regulated in telomerase-positive chES cells. Transcription levels of chTERT, chTR, and c-myc are dramatically up-regulated in telomerase-positive DT40 cells, relative to CEFs and chES cells. These results are consistent with a model in which telomerase activity is up-regulated in proliferating embryonic stem cells requiring stable telomeres to endure multiple rounds of cell division; down-regulated in differentiated, lifespan-limited cells; and dramatically up-regulated in immortalized, transformed cells for which uncontrolled proliferation is correlated with c-myc dysregulation and telomerase activity.

We have designed and characterized two new replication-competent avian sarcoma/leukosis virus-based retroviral vectors with amphotropic and ecotropic host ranges. The amphotropic vector RCASBP-M2C(797-8), was obtained by passaging the chimeric retroviral vector RCASBP-M2C(4070A) (6) in chicken embryos. The ecotropic vector, RCASBP(Eco), was created by replacing the env-coding region in the retroviral vector RCASBP(A) with the env region from an ecotropic murine leukemia virus. It replicates efficiently in avian DFJ8 cells that express murine ecotropic receptor. For both vectors, permanent cell lines that produce viral stocks with titers of about 5 x 10(6) CFU/ml on mammalian cells can be easily established by passaging transfected avian cells. Some chimeric viruses, for example, RCASBP(Eco), replicate efficiently without modifications. For those chimeric viruses that do require modification, adaptation by passage in vitro or in vivo is a general strategy. This strategy has been used to prepare vectors with altered host range and could potentially be used to develop vectors that would be useful for targeted gene delivery.

The interactions between the subgroup A avian leukosis virus [ALV(A)] envelope glycoproteins and soluble forms of the ALV(A) receptor Tva were analyzed both in vitro and in vivo by quantitating the ability of the soluble Tva proteins to inhibit ALV(A) entry into susceptible cells. Two soluble Tva proteins were tested: the 83-amino-acid Tva extracellular region fused to two epitope tags (sTva) or fused to the constant region of the mouse immunoglobulin G heavy chain (sTva-mIgG). Replication-competent ALV-based retroviral vectors with subgroup B or C env were used to deliver and express the two soluble tv-a (stva) genes in avian cells. In vitro, chicken embryo fibroblasts or DF-1 cells expressing sTva or sTva-mIgG proteins were much more resistant to infection by ALV(A) ( approximately 200-fold) than were control cells infected by only the vector. The antiviral effect was specific for ALV(A), which is consistent with a receptor interference mechanism. The antiviral effect of sTva-mIgG was positively correlated with the amount of sTva-mIgG protein. In vivo, the stva genes were delivered and expressed in line 0 chicken embryos by the ALV(B)-based vector RCASBP(B). Viremic chickens expressed relatively high levels of stva and stva-mIgG RNA in a broad range of tissues. High levels of sTva-mIgG protein were detected in the sera of chickens infected with RCASBP(B)stva-mIgG. Viremic chickens infected with RCASBP(B) alone, RCASBP(B)stva, or RCASBP(B)stva-mIgG were challenged separately with ALV(A) and ALV(C). Both sTva and sTva-mIgG significantly inhibited infection by ALV(A) (95 and 100% respectively) but had no measurable effect on ALV(C) infection. The results of this study indicate that a soluble receptor can effectively block infection of at least some retroviruses and demonstrates the utility of the ALV experimental system in characterizing the mechanism(s) of viral entry.

Primary carcinoid tumors of the mediastinum were described for the first time in 1972 as thymic carcinoids. Our experience with 16 patients who underwent diagnostic and surgical procedures at the Mayo Clinic is presented. All of these patients had mediastinal carcinoid. The surgical procedures included node biopsy, anterior mediastinotomy (Chamberlain), median sternotomy and posterior lateral thoracotomy. Complete resection was possible in 9 (56.3%) patients, 3 (18.7%) had partial removal (debulking), and 4 (25%) had diagnostic biopsies only. The operative morbidity was 25%. There were no postoperative deaths. In resectable patients, the average disease free interval was 45.7 months. Five year and ten year survival was 47% and 22%, respectively. Local or distant metastatic spread developed in all patients (100%). Mediastinal carcinoids are a separate entity from other thymic and mediastinal neoplasms. (We suggest that) Surgical excision may be possible earlier in the disease and radiation and chemotherapy are of doubtful value.

Over 900 patients have been treated at the Mayo Clinic for Zenker's diverticulum since 1944 using a one-stage transcervical diverticulectomy under general anesthesia. Overall results have been very good, but not entirely free of morbidity or mortality. An attempt is made to define those circumstances in which the procedures used have either been judgmentally or technically difficult or in which morbidity or mortality has occurred. These include patients with concomitant medical or surgical problems, or complexity related to the diverticulum itself. Among the latter are huge or giant sacs, patients with severe nutritional and respiratory symptoms related to aspiration, the perforated diverticulum, reoperation for recurrent diverticulum and cancer in a diverticulum.

Polypeptides of hemorrhagic enteritis virus (HEV) of turkeys and marble spleen disease virus (MSDV) of pheasants were analyzed by immune precipitation and immunoblot assays. A total of 11 polypeptides ranging in molecular weight from 14,000 to 97,000 were detected in lysates of HEV-infected turkey cells analyzed by immunoblot assay using a polyclonal antibody against HEV. Identical patterns were observed with preparations of MSDV. Five monoclonal antibodies (MAbs) against HEV were chosen based on their virus neutralization activity and used for identification of neutralizing epitopes of these two viruses. Three MAbs precipitated a single 97,000-molecular-weight hexon polypeptide in an immune precipitation assay.

The National Cancer Institute of the United States recently sponsored three large-scale, randomized controlled trials of screening for early lung cancer. The trials were conducted at the Johns Hopkins Medical Institutions, the Memorial Sloan-Kettering Cancer Center, and the Mayo Clinic. Participants were middle-aged and older men who were chronic heavy cigarette smokers and thus at high risk of developing lung cancer. Screening procedures were chest radiography and sputum cytology, the only screening tests of established value for detecting early stage, asymptomatic lung cancer. In the Hopkins and Memorial trials the study population was offered yearly chest radiography plus sputum cytology every 4 months. The control population was offered yearly chest radiography only. In these trials the addition of sputum cytology appeared to confer no lung cancer mortality rate advantage. The Mayo Clinic trial compared offering chest radiography and sputum cytology every 4 months to offering advice that the two tests be obtained once a year. This trial demonstrated significantly increased lung cancer detection, resectability, and survivorship in the group offered screening every 4 months compared with the control group. However, there was no significant difference in lung cancer mortality rate between the two groups. The statistical power of these trials was somewhat limited. Nevertheless, results do not justify recommending large-scale radiologic or cytologic screening for early lung cancer at this time.

Primary pulmonary artery sarcoma classically presents with symptoms and findings suggestive of acute pulmonary artery occlusion. An angiocentric mass or the finding of spindling neoplasm on needle biopsy should suggest this neoplasm. The rare unilateral location in the present case permitted resection by pneumonectomy. An endarterectomy technique was used to extract loosely adherent tumor-thrombus from the more proximal portions of the left pulmonary artery.

During a 13-year period, multiple primary lung cancers were diagnosed in 80 consecutive patients. Forty-four patients had metachronous cancers. The initial pulmonary resection was lobectomy in 36 patients, bilobectomy in 3, pneumonectomy in 1, and wedge excision or segmentectomy in 4. The second pulmonary resection was lobectomy in 16 patients, bilobectomy in 2, completion pneumonectomy in 7, and wedge excision or segmentectomy in 19. There were two 30-day operative deaths (mortality rate, 4.5%). Actuarial 5- and 10-year survival rates after the first pulmonary resection for stage I disease were 55.2% and 27.0%, respectively. Five-year and 10-year survival rates for stage I disease after the second pulmonary resection were 41.0% and 31.5%, respectively. The remaining 36 patients had synchronous cancers. The pulmonary resection was lobectomy in 18 patients, bilobectomy in 3, pneumonectomy in 10, and wedge excision or segmentectomy in 8. There were two 30-day operative deaths (mortality rate, 5.6%). Actuarial overall 5- and 10-year survival rates after pulmonary resection were 15.7% and 13.8%, respectively. We conclude that an aggressive surgical approach is safe and warranted in most patients with multiple primary lung cancers and that the presence of synchronous primary cancers is ominous.

A highly sensitive and specific double-antibody enzyme-linked immunosorbent assay (ELISA) is described for the detection of antigen and antibody of turkey hemorrhagic enteritis virus (HEV). The assay utilizes a virus-neutralizing monoclonal antibody (MAb) to capture the antigen and turkey antiserum against HEV as the second antibody. Microtiter plates were first coated with a dilution of 1:3000 of the MAb (300 ng immunoglobulin/well) and are used for detection of both antigen and antibody. For antibody detection, MAb-coated plates were treated with an appropriate dilution of a cell-culture-propagated HEV antigen and then reacted with the test turkey serum. For detection of HEV antigen, MAb-coated plates were treated with appropriate dilutions of test antigens and then reacted with purified anti-HEV turkey immunoglobulins. The assay for HEV antibody detection was more sensitive and specific than previously described single-antibody ELISAs. Using the double-antibody ELISA, it was found that the spleen of HEV-infected turkeys harbors very high levels of antigen. Traces of HEV antigen are present in some other organs. Infectivity assay for HEV is found to be about two orders of magnitude more sensitive than the ELISA for detection of virus.

In this article, we describe an integrated approach for detection and evaluation of solitary pulmonary nodules. Initial evaluation of the solitary pulmonary nodule includes tomography, fluoroscopy, and comparison with previously obtained roentgenograms. Subsequently, thin-section computed tomography and phantom densitometry can be used for analysis, if indicated. The rationale for the use of computed tomography in the radiologic staging of bronchogenic carcinoma is to expedite and assist in the identification of the subset of patients with resectable tumors. For nonsurgical tissue diagnosis, fiberoptic bronchoscopy is generally the initial procedure for lesions 2.0 cm or larger in diameter, and transthoracic needle biopsy is used for those smaller than 2.0 cm.

One hundred and one patients with benign, reflux-induced oesophageal stenosis were surgically treated at the Mayo Clinic during a recent 6 year period by the author. In 71 patients, the stenosis was readily dilated and treated by a variety of antireflux procedures, depending on presence or absence of oesophageal peristalsis or acquired shortening of the oesophagus. Thirteen additional patients were managed by gastric secretion suppression with duodenal diversion using the Roux-Y principle. Seventeen patients with undilatable stenoses were managed by resection and a variety of reconstructions. The modified Ivor-Lewis procedure with or without thoracotomy was the procedure employed in 12 of the 17 with the remainder managed with either substernal colon or upper digestive secretion suppression-diversion. These 101 operations were accomplished without mortality and all but one patient have resumed an oral diet and returned to their usual occupation. While 91 per cent of the 101 patients are free of reflux symptoms or demonstrable stenosis and are considered improved, only 83 per cent of all patients have "excellent' to "good' late results in terms of both oesophageal and gastrointestinal symptoms.

From 1958 through 1985, a total of 113 consecutive patients had completion pneumonectomy (CP). Indications for pulmonary resection resulting in CP were lung cancer (LC) in 64 patients, pulmonary metastases (PM) in 20, and benign lung disease (BLD) in 29. Operative mortality was 12.4% (14 deaths) but varied according to the indication for CP. Mortality was 9.4% for LC, 0% for PM, and 27.6% for BLD. Forty-three patients (38.1%) had major complications (26 of 64 with LC, 40.6%; 1 of 20 with PM, 5.0%; and 16 of 29 with BLD, 55.2%). Five-year actuarial survival for patients with LC was 26.4% but varied according to stage. Five-year survival for patients with PM was 40.8% and with BLD was 27.2%. We conclude that CP for BLD carries marked operative mortality and morbidity, usually due to intense reaction around hilar structures and concurrent active infection or fistula. In contrast, CP for LC and PM can be performed with low mortality, acceptable morbidity, and gratifying long-term survival.

Two hundred ninety-three patients were randomly assigned to three treatment regimens following mastectomy for operable but prognostically unfavorable breast cancer: L-PAM, CFP, or CFP with radiation therapy. For premenopausal patients an increased risk of recurrence was associated with the presence of unfavorable local signs, large number of lymph nodes involved, greater body weight, younger age, and L-PAM treatment. For the postmenopausal patients only three factors were associated with an increased risk of recurrent disease: large tumor size, large number of lymph nodes involved, and inner/central location of the primary lesion. Specifically, the treatment employed has shown no effect. Of particular importance is the fact that for neither group of patients does our experience presently demonstrate clear association of recurrent disease with the level of drug dose administered. Furthermore, evidence suggests that although patients who experience little or no myelosuppression have significantly worse disease-free intervals than patients who experience moderate or severe myelosuppression, here is no benefit for severe myelosuppression over moderate, myelosuppression.

A young adult with a congenital H-type tracheoesophageal fistula complicated by achalasia of the esophagus presented with complaints consistent with existing long-standing asthma. Only on direct questioning were esophageal aspects elicited. This combination of conditions proved difficult to diagnose even though suspected. Esophageal x-ray in the prone-oblique position proved valuable in the diagnosis and localization of the fistula. Correction of the obstruction of achalasia preceded fistula repair. Fistula repair involved sleeve resection of the trachea, with tracheal anastomosis after closure of the esophageal defect.

To study the effectiveness of a trend at the Mayo Clinic toward modifying the standard radical mastectomy, the 5-year survival of 873 women treated surgically for breast cancer from 1965 through 1968 was evaluated. The observed survival of 534 patients treated by the standard radical mastectomy was 85% when nodes were negative and 56% when nodes were positive. For 339 patients treated by the modified radical mastectomy, the observed survival was 80% and 48% when axillary nodes were negative and positive, respectively. In order to accomplish a more significant analysis of cancer risk and results of the two operative procedures, a relatively homogeneous group of 541 patients was established from the total group. In this homogeneous group, the observed survival of 336 patients treated by the standard radical mastectomy was 86% when nodes were negative and 66% when nodes were positive. For 205 patients treated by the modified radical mastectomy, the observed survival was 84% and 66% when axillary nodes were negative and positive, respectively. When patients were further analyzed and compared according to the extent of axillary-node involvement, age at the time of treatment, grade, size, location, and histopathologic type of tumor, and the use of postoperative irradiation, survival was essentially the same, irrespective of the type of mastectomy performed.

One hundred adult patients underwent Ivor Lewis esophagogastrectomy for documented carcinoma of the esophagus from 1980 through 1982. After operation, 7 patients were classified in Stage I, 11 in Stage II, and 82 in Stage III. Major postoperative complications occurred in 27 patients and included pulmonary problems in 11, suture line leak in 9, wound infection in 5, empyema in 4, renal failure in 4, abdominal abscess in 4, bleeding in 2, myocardial infarction in 2, and chylothorax in 1. There were 3 deaths within 30 days of operation. Five-year survival was 85.7% for patients with Stage I disease, 34.1% for patients with Stage II disease (p = .052), and 15.2% for patients with Stage III disease (p = .001). Late morbidity included weight loss in 60 patients, dysphagia in 40, gastroesophageal reflux in 14, and gastroduodenal dumping in 5. Thirty-one patients required postoperative esophageal dilations (mean, 3.4). Most patients, however, were eating without dysphagia at the time of last follow-up or death. We conclude that the Ivor Lewis esophagogastrectomy can be performed with low mortality, can provide adequate palliation, and does result in satisfactory long-term survival for those patients with more favorable postsurgical stages of cancer. These results support the continued use of the Ivor Lewis esophagogastrectomy for treatment of carcinoma of the esophagus.

A middle-aged man with long-standing polyostotic fibrous dysplasia had severe progressive restrictive lung disease with hypoxemia and pulmonary hypertension with heart failure because of exuberant intrathoracic, extraosseous proliferation of dysplastic tissue. Subtotal resection of this benign tissue mass ameliorated the respiratory insufficiency and led to sustained improvement in exercise tolerance, increase in pulmonary reserve, and decrease in signs of heart failure and pulmonary hypertension.

Sixty-six patients (54 men and 12 women) with primary bronchogenic carcinoma and documented chest wall invasion underwent en bloc chest wall and pulmonary resection at the Mayo Clinic between January 1, 1960, and January 1, 1980. Ages ranged from 36 to 85 years, with a mean of 62.2. Forty-eight lobectomies, 16 pneumonectomies, and 2 wedge excisions were performed. After operation, 31 patients were classified as T3 N0 M0, 7 as T3 N1 M0, and 12 as T3 N2 M0. In 16 patients, the N classification could not be determined (T3 Nx M0). Operative mortality was 15.2%. Actuarial five-year survival (Kaplan-Meier method) of the 56 patients surviving operation was 32.9%. Five-year survival for patients with T3 N0 M0 neoplasms was 53.7%; five-year survival for patients with N1 and N2 neoplasms was only 7.4% (p = 0.001). The effect of various factors on survival, both singularly and in combination, was assessed by Cox's proportional hazards model. Only age had a significant association with survival. Among patients with T3 N0 M0 neoplasms, five-year survival was 84.6% for those 60 years of age or less and 27.7% for patients who were older than 60 years (p = 0.009). We conclude that en bloc resection for primary bronchogenic carcinoma with chest wall invasion, while associated with a significant mortality, can be performed with a strong likelihood of long-term survival if regional lymph nodes are not metastatically involved and there is no evidence of distant metastasis.

Between 1955 and 1975, chest wall resection was done in 90 patients for primary chest wall tumors. Ages ranged from 8 to 96 years (mean, 44.3 years). A painful mass was the most common sign and symptom. Eighty-two tumors (91.1%) were located in the lateral chest wall and eight, in the anterior thorax. The tumor was malignant in 71 patients (78.9%) and benign in 19. All patients with benign tumors had complete excision and are currently free from disease. Malignant fibrous histiocytoma, chondrosarcoma, and rhabdomyosarcoma constituted 62% of the malignant neoplasms. Most malignancies were treated by wide resection. There were no thirty-day operative deaths. Overall 1-, 5-, and 10-year survival was 89%, 57%, and 49%, respectively. Recurrent tumor developed in 37 patients (52%); 5-year survival, however, was only 17% after recurrence. Cell type and extent of invasion significantly influenced survival. Both chondrosarcoma and rhabdomyosarcoma had a better prognosis than malignant fibrous histiocytoma (p less than 0.05). We conclude that early resection is the treatment of choice for primary malignant chest wall tumors and that development of recurrent disease is an ominous event.

Experience with 47 consecutive instrumental perforations of the esophagus is described. Perforation occurred in the cervical esophagus in 18 patients, mid-thoracic esophagus in 12, and distal esophagus in 17. The majority of patients (87%) harbored a primary esophageal disorder necessitating esophageal instrumentation. Eight select patients were treated nonoperatively with one death; however, some form of morbidity with prolonged hospital stay occurred in half of these patients. In contrast, 39 patients underwent emergency surgical intervention. Only one death occurred in the 31 patients treated by local drainage and attempted closure of the perforation. However, three of six patients with distal perforations treated by esophageal resection with primary esophagogastrostomy died in the early postoperative period. Our results suggest that most instrumental perforations of the esophagus should be managed surgically. Drainage and closure of cervical perforations yields goods results. Esophageal resection with primary reconstitution of esophagogastric continuity should be reserved for select situations. Nonoperative management might be entertained in minimally symptomatic patients harboring a late, locally contained perforation without signs of ongoing sepsis.

Cancers of the esophagus and cardia remain serious conditions that cause many thousands of deaths every year throughout the world. In North America, cancer of the esophagus and gastric cardia is an endemic disease of low order and stable incidence. Nevertheless, it is responsible for many deaths and considerable suffering. With current methods of treatment, substantial palliation and amelioration of patient disability are possible, and some patients gain long-term survival with comfort and even cure. A combination of surgical resection and reconstruction is the chief modern method of management of such cancers. Herein we discuss a variety of standard surgical procedures that are currently available and present detailed illustrations of these procedures. The selection of a specific operation depends largely on the site of the neoplasm. With all these procedures, function is restored and the local and regional neoplastic tissue is removed without compromising the potential for cure. Associated operative mortality is approximately 7%. The late results of the operations illustrated depend primarily on the cell type, grade, and stage of the neoplasm encountered at the time of surgical treatment. For patients who have undergone resection, 5-year survival rates have ranged from 15 to 54%, the results depending on the stage of the cancer. Of equal importance is the fact that oral diet can be maintained in 93% of patients despite recurrence of the neoplasm.

The records of all patients in whom a mastectomy was performed for carcinoma of the breast at this clinic during a recent two year period were reviewed, and the gross specimens were re-examined to study the incidence of cancerous involvement of the nipple and areola and related local clinical findings. Cancer was present in the nipple or areola, or both, in 12.2 per cent of the specimens. When the nipple and areola were clinically normal, involvement of the nipple and areola by carcinoma was rare if the primary tumor was less than 2 centimeters in diameter and was not situated behind the areola.

Aggressive resection, with individualized reconstruction by several methods, is of value in many patients with radiation necrosis and/or advanced breast cancer of the chest wall. Although this does not always significantly lengthen survival, it can improve the quality of life markedly in many instances. Remarkably large defects can be reconstructed with single-stage procedures.

The effectiveness of fibrin glue as a biological sealant for pulmonary air leaks was determined in 16 dogs. A standardized pleural defect was made in the left lower lobe, and the quantity of air passing through a chest tube was assessed with a Collins respirometer. For the 8 randomly assigned control animals, the air leak decreased over 90 minutes from a mean of 1.4 L/min to a mean of 1.1 L/min (mean decrease, 19.8%). In the 8 randomly assigned fibrin glue-treated animals, the air leak decreased from a mean of 2.1 L/min to a mean of 0.5 L/min (mean decrease, 80.8%) (p less than 0.0001). Postoperative evaluation of survivors disclosed no increased adhesions in the glue-treated animals and complete resorption of the glue at 3 months. We conclude that in this animal model, fibrin glue reduced the size of pulmonary air leaks in the early period after thoracotomy and did not lead to increased intrapleural adhesions.

When the TNM staging system of the American Joint Committee (AJC) for Cancer Staging and End-Results Reporting was applied to 3,912 patients seen during a 6 year period at the Mayo Clinic, 624 (16%) fulfilled the criteria for postsurgical pathological Stage I non-small cell bronchogenic carcinoma. Of these 624 patients, 129 were excluded from further survival analysis for various reasons. The remaining 495 consisted of two groups: 350 patients who were enrolled within 30 days into a prospective postoperative 4 monthly follow-up program and 145 patients who were enrolled later or were followed less frequently. Because no significant difference was noted in survival rates between these groups, data were pooled. Of the combined group of 495 patients, 84% survived lung cancer for 2 years and 69% of 5 years (actuarial estimation). The survival of patients classified T1 N0 M0 (91% alive at 2 years and 80% at 5 years) is so good that it seems unlikely that adjuvant therapy in this group could demonstrate improved survival. In addition to TNM classification, age at operation, sex, and extent of operation were important determinants of survival.

An arteriovenous fistula between the systemic and pulmonary circulations may be congenital, as in bronchopulmonary sequestration, or the communication may be acquired. Inflammatory disease, trauma, and, rarely, neoplasm have been implicated as possible causes of acquired communications. We describe a patient who had a systemic artery-to-pulmonary vein fistula that was secondary to a recurrent sarcoma of the chest wall. Review of the literature failed to reveal a previous report of a similar case.

Fifty-six patients with chronic intestinal ischemia underwent surgical revascularization. All patients had abdominal pain, 98% experienced significant weight loss, and 75% had an abdominal bruit. Visceral artery occlusive disease was documented by angiography in all patients; 77% of our patients had multiple-vessel occlusive disease, and 23% had single-vessel involvement of either the celiac or the superior mesenteric artery. The mortality rate was 8.9%. Ninety-six percent of the survivors were completely relief of symptoms, but an overall late recurrence rate was noted in 26.5%. Fifty-nine percent of our patients underwent revascularization of all stenotic vessels. Complete revascularization in multiple-vessel disease resulted in a late recurrence rate of 11%. When two of three stenotic vessels were revascularized, there was a 29% recurrence rate, and when one of three stenotic vessels was revascularized, there was a 50% recurrence rate. These findings suggest that although single-vessel revascularization may relieve symptoms, the optimal long-term result can be obtained by complete revascularization of all stenotic vessels.

Continuous in vitro propagation of a producer Marek's disease (MD) lymphoblastoid cell line reduced the number of cells producing virus antigens and the inducibility of these antigens to 5-iododeoxyuridine (IUDR) but did not change the oncogenicity of the cells for chickens. In contrast, propagation of a non-producer MD cell line did not change the non-productivity of the cell line, but decreased the transplantability of the cells. The MD lines were free of replicating avian leukosis sarcoma viruses (LSV) and were susceptible to infection with LSV of subgroup A.