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Larry R Kaiser

Publications and source records attributed to Larry R Kaiser.

At least 55 records · Page 3Linked to original sources
PubMed2003

WW domain containing oxidoreductase gene expression is altered in non-small cell lung cancer.

WWOX (WW domain containing oxidoreductase), a putative tumor suppressor gene that maps to the common fragile site FRA16D on chromosome 16q23.3-24.1, is altered in breast, esophageal, and ovarian cancer. Because the FRA3B/FHIT locus at 3p14.2 is a preferential target for genetic changes caused by tobacco smoke, we intended to evaluate the status of the FRA16D/WWOX gene in non-small cell lung cancer; we have analyzed 27 paired normal and tumor lung tissues and 8 lung cancer cell lines for WWOX alterations by reverse transcriptase-PCR, loss of heterozygosity, and mutation analysis. Transcripts missing WWOX exons were detected in 7 primary tumors (7 of 27; 25.9%) and 5 of 8 cell lines. In addition, loss of heterozygosity at the WWOX locus was observed in 10 primary tumors (10 of 27; 37.0%). We conclude that WWOX alterations occur in a significant fraction of lung cancers and may contribute to the pathogenesis of non-small cell lung cancer.

Carcinoma, Non-Small-Cell Lung↗
PubMed2003

Weerda diverticuloscope: novel use to remove embedded esophageal foreign bodies.

Embedded sharp foreign bodies of the cervical esophagus represent a clinical challenge. Initial attempts at removal are usually undertaken by nonsurgical endoscopists who are often successful with blunt objects. Unsuccessful attempts with sharp objects, however, can result in distal migration, mucosal damage, and frank perforation. Thoracic surgeons are often called on for cervical esophagotomy after endoscopic attempts have failed. This report describes the novel use of a Weerda diverticuloscope for removal of a dental appliance with metallic hooks embedded in the cervical esophagus.

Adult↗
PubMed2003

Bronchial sleeve resection for posttransplant stricture.

Nonanastomotic bronchial stenosis is a rare complication of lung transplantation. We report a case of a bilateral lung transplant recipient who experienced recalcitrant stenosis of the bronchus intermedius. All attempts at conservative management failed, and the stricture was successfully treated by a parenchymal-sparing segmental sleeve resection. Although rare, this is an important technique in the management of this difficult problem.

Bronchi↗
PubMed2003

Comparison of stages I-II thymoma treated by complete resection with or without adjuvant radiation.

BACKGROUND: Adjuvant radiation after resection of Masaoka stage II thymoma is widely advocated, but the evidence supporting it is controversial. Studies addressing this issue generally report few patients and lump all patients beyond stage I together in the analysis. METHODS: We retrospectively compared outcomes of stage I and II thymomas treated by resection alone with thymomas treated by resection plus radiation. Histology was re-reviewed to confirm pathologic staging and resection margin status. RESULTS: Between February 1992 and 2002, we performed 167 resections for thymoma. Of these, 70 patients were believed to have tumors in stage IIb or less intraoperatively, and all of these patients underwent complete resection. We reviewed the histopathology of 62 of 70 patients. Thirty thymomas demonstrated less than complete transcapsular microscopic invasion (stage I) and 40 thymomas demonstrated microscopic transcapsular invasion or macroscopic invasion into surrounding fatty tissue (stage II). Forty-seven patients underwent surgery without postoperative mediastinal radiotherapy. Dosages in the 23 radiated patients (3 stage I and 20 stage II) consisted of 45 to 55 Gy. Median follow-up was 70.3 months. Stage II patients who were radiated (n = 20) and those who were not radiated (n = 20) consisted of identical proportions in stages IIa and IIb. Two patients recurred (1 unradiated stage I patient and 1 radiated stage IIb patient). Overall 5-year survival rate was 91%. All who died were free of recurrence at time of death. Log-rank test showed no difference in Kaplan Meier survival curves (p = 0.32) between the radiated and unradiated groups. CONCLUSIONS: These data support the contention that margin-negative surgical resection alone is sufficient treatment for both stages I and II thymoma.

Adult↗
PubMed2003

Suramin inhibits the growth of malignant mesothelioma in vitro, and in vivo, in murine flank and intraperitoneal models.

Surgical debulking of malignant mesothelioma (MM) ultimately fails due to local recurrence. Suramin, an inhibitor of extracellular growth factors (ECGFs), has demonstrated efficacy in the treatment of malignant mesothelioma in a small case series. Our goal was to study survival benefits and disease progression in several MM animal models treated with suramin as a potential agent for adjuvant therapy. In vitro growth of human (REN, I-45), rat (II-45) and murine (AB12) mesothelioma cell lines were measured with or without suramin exposure. Human and murine MM tumors were implanted subcutaneously into murine flanks or injected intraperitoneally (i.p.) into murine abdominal cavities. Dose and treatment schedules were optimized to reduce the rate of tumor progression and to improve survival curves. Suramin inhibited the in vitro growth of all cell lines, reaching statistical significance (P<0.01) three doubling cycles after suramin administration, with a maximum inhibition of 10-25% of control growth. A significant time- and dose-dependent effect was observed. In vivo, suramin inhibited the growth of MM in the xenogeneic model (55% of control growth, P<0.01), and in the syngeneic model at both the low and high loading doses (46 and 36% of control growth, respectively, P<0.01). Suramin treatment inhibited in vivo growth in the REN intraperitoneal model shown grossly by necropsy of same day deaths comparing treatment and control animals. Tumor inhibition with the higher dose was also reflected by the lower mean tumor burden scores (control: 4.0 and high dose: 3.4). Suramin inhibits the growth of human, murine, and rat MM in vitro, in a time- and dose-dependent manner. Suramin also inhibits the growth of human MM flank and intraperitoneal xenografts in vivo in an immunodeficient host, as well as the growth of syngeneic murine flank tumors in an immunocompetent host. These studies demonstrate that suramin may have the potential to provide effective therapy for MM, and that further studies are necessary to elucidate the survival advantage of suramin mediated MM growth inhibition.

Animals↗
PubMed2003

Giant bullous lung disease: evaluation, selection, techniques, and outcomes.

Patient selection remains one of the most important aspects of successful surgery for bullous disease. Operation is indicated for patients who have incapacitating dyspnea with large bullae that fill more than 30% of the hemithorax and result in the compression of healthy adjacent lung tissue. Operation is also indicated for patients who have complications related to bullous disease such as infection or pneumothorax. Patients who have bullous disease in the presence of diffuse lung disease (emphysematous or nonemphysematous) should be evaluated on an individual basis and surgery should be performed on patients in whom even a small increase in pulmonary function might be of major benefit. Smoking cessation and outpatient pulmonary rehabilitation are required of all patients preoperatively. Patients should undergo PFTs including lung volumes by whole body plethysmography, spirometry, diffusion capacity, and arterial blood gas. CT remains the most important preoperative evaluation because it is useful assessing the extent of bullous disease and the quality of the surrounding lung tissue. The authors favor a minimally invasive technique through VATS whenever possible because it might allow for a quicker recovery and might be associated with less pain than is seen following thoracotomy. Modified Monaldi-type drainage procedures are also effective, especially in high-risk patients who cannot tolerate excisional procedures. Special care must be taken to avoid sacrifice of any potentially functional lung tissue. Lobectomies should be avoided whenever possible. The best results are seen in limited resections of large bullae that spare all surrounding functional pulmonary parenchyma. Postoperative complications are minimized through aggressive tracheobronchial toilet and vigorous chest physiotherapy. Adequate pain control in maintained throughout the postoperative period, initially by way of epidural infusion of morphine or fentanyl and later through oral opioids. Early ambulation and pulmonary rehabilitation also help minimize complications.

Drainage↗
PubMed2003

Adenovirus-mediated gene transfer of enhanced Herpes simplex virus thymidine kinase mutants improves prodrug-mediated tumor cell killing.

The Herpes simplex virus 1 (HSV) thymidine kinase (tk) suicide gene together with ganciclovir (GCV) have been successfully used for the in vivo treatment of various solid tumors and for the ablation of unwanted transfused stem cells in recent clinical trials. With the aim of improving this therapeutic system, we compared the potential efficacy of adenoviral (Ad) vectors expressing enhanced tk mutants in vitro and in vivo. The previously created HSV-tk mutants dm30 and sr39, created by random sequence mutagenesis, were inserted into a standard Ad.RSV E1(-)E3(-) backbone using homologous recombination. GCV killing of Ad.HSV-tk, Ad.dm30-tk and Ad.sr39-tk was assessed in various tumor cell lines with a cell proliferation assay. Cells expressing the two TK mutants were two-to-five-fold more sensitive to GCV when compared with Ad.HSV-tk transduced cells in all cell lines tested (five human mesotheliomas, one human lung cancer, a human cervical carcinoma, a mouse fibrosarcoma, and a rat glioma line) at equal TK expression levels. Flank tumor models, including cell-mixing studies, assessed the in vivo efficacy of the engineered viruses in BALB/C and SCID mice. In all animal studies, Ad.dm30-tk and Ad.sr39-tk showed more tumor growth inhibition than Ad.HSV-tk when GCV was administered. The use of adenovirus-mediated gene transfer of both tk mutants dm30-tk and sr39-tk for cancer suicide gene therapy should provide a more effective and safer alternative to wild-type HSV-tk.

Adenoviridae↗
PubMed2003

TRANCE- and CD40 ligand-matured dendritic cells reveal MHC class I-restricted T cells specific for autologous tumor in late-stage ovarian cancer patients.

PURPOSE: The use of mature dendritic cells (DCs) presenting tumor-associated antigens (TAAs) to trigger tumor-specific T cells in vivo or in vitro represents a promising approach for cancer immunotherapy. We hypothesized that tumor antigens, mostly unidentified, are present on ovarian tumor cells and that mature DCs could be used to generate tumor-specific responses in unprimed patients. We also sought to measure preexisting antitumor immunity in patients with advanced ovarian cancer. EXPERIMENTAL DESIGN: Autologous DCs from 10 patients with ovarian cancer were pulsed with killed autologous primary tumors as a source of TAAs. DCs were then cultured in the presence of tumor necrosis factor alpha + TRANCE (tumor necrosis factor-related activation-induced cytokine) to induce maturation. Mature TAA-pulsed DCs were used in vitro to stimulate tumor-specific peripheral blood T cells. RESULTS: TRANCE and CD40 ligand were effective at maturing DCs. T-cell lines were generated in vitro that were capable of secreting IFN-gamma in response to autologous tumor. These tumor-specific T cells were MHC class I restricted. The frequency of tumor-specific T cells in uncultured cells from malignant ascites fluid and peripheral blood was measured in the same patients. CONCLUSIONS: IFN-gamma-secreting tumor-specific T cells were demonstrated at baseline in uncultured T cells from some unvaccinated ovarian cancer patients; however, the T cells could not kill autologous tumor. These data demonstrate that mature DCs presenting tumor antigens from engulfed autologous tumors can be used to augment antitumor immunity in vitro in patients with epithelial ovarian cancer. The results support the feasibility of therapeutic vaccination of ovarian cancer patients.

Adult↗
PubMed2002

Cutting edge: Regulatory T cells from lung cancer patients directly inhibit autologous T cell proliferation.

Active suppression by T regulatory cells plays an important role in the down-regulation of T cell responses to foreign and self-Ags. Thus far, the potential role of CD4(+)CD25(+) T cells in human tumors has not been reported. In this work we show that lung tumors contain large numbers of these cells and that they have constitutive high-level expression of CD152 (CTLA-4). Furthermore, the CD4(+)CD25(+) T cells mediate potent inhibition of autologous T cell proliferation. Finally, regulatory T cells from patient tumors failed to inhibit the proliferation of allogeneic T cells. Together these results suggest that the CD4(+)CD25(+) T cells found in lung tumors selectively inhibit the host immune response and therefore could contribute to the progression of lung cancer.

Abatacept↗
PubMed2002

Current presentation and optimal surgical management of sternoclavicular joint infections.

BACKGROUND: Infection of the stemoclavicular joint is unusual, and treatment of this entity has not been standardized. We sought to characterize the current presentation and optimal management of this disease. METHODS: We retrospectively reviewed the records of the last 7 patients undergoing operation for suppurative infections of the stemoclavicular joint at this institution. Patients were interviewed regarding upper extremity function after formal joint resection. RESULTS: Predisposing factors were common and included diabetes mellitus (n = 2), clavicular fracture (n = 1), human immunodeficiency virus infection (n = 1), immunosuppression (n = 1), and pustular skin disease (n = 1). All patients presented with local symptoms including clavicular mass and tenderness. Diagnosis and evaluation were facilitated by cross-sectional imaging. Organisms isolated included Staphylococcus aureus, group G streptococcus, and Proteus and Propionibacterium species. Antibiotic therapy and simple drainage and debridement were generally ineffective, leading to recurrence of infection in 5 of 6 patients treated initially in this manner. Six patients were treated with resection of the stemoclavicular joint and involved portions of first or second ribs with soft tissue coverage by advancement flap from the ipsilateral pectoralis major muscle. Response to this therapy was excellent, with cure in all patients, no wound complications, and excellent upper extremity function at long-term follow-up. CONCLUSIONS: Aggressive surgical management including resection of the sternoclavicular joint and involved ribs with pectoralis flap closure would appear to be the preferred treatment for all but the most minor infections of the sternoclavicular joint. This approach has minimal impact on upper extremity function.

Adult↗
PubMed2002

Thoracic surgery workforce: snapshot at the end of the twentieth century and implications for the new millennium.

BACKGROUND: An appropriately sized physician workforce is an essential component for healthcare planning. Contemporary economic forces and the impact of managed care have stimulated renewed interest in understanding and monitoring workforce issues. METHODS: Between August and December of 1999, the Workforce Committee of the American Association for Thoracic Surgery and The Society of Thoracic Surgeons conducted a survey detailing demographic, geographic, and socioeconomic practice characteristics of the membership. RESULTS: The 2,515 returned surveys represented a 62.6% return rate (+/- 1.6% margin of error), providing a highly statistically valid sample. Active thoracic surgeons are a mean of 50 years old, 98% men, with a high level of career satisfaction. Length of training and educational debt has been escalating. Adult cardiac surgical case volumes have increased (mean, 225 cases) and 52% of adult cardiac surgeons perform general thoracic procedures. Surgeons work 67 hours/week and 47 weeks/year. Most are organized in single specialty groups (50%) in urban areas (59%) as for-profit corporations (77%). Half of the respondents will be retired a mean of 13 years from now corresponding to a median calendar year of 2011. CONCLUSIONS: This survey highlights significant workforce retirement during the next 10 to 15 years. Currently, the workforce in thoracic surgery appears "right sized." These valuable data provide a profile of the specialty. The information enhances our ability to strategically plan.

Adult↗
PubMed2002

Transcervical thymectomy for myasthenia gravis achieves results comparable to thymectomy by sternotomy.

BACKGROUND: It remains controversial whether transcervical thymectomy offers results equivalent to thymectomy by way of a median sternotomy in the treatment of myasthenia gravis. Furthermore, preoperative prognostic factors have not been clearly defined. METHODS: This study is a retrospective chart review and interview of 78 patients completing transcervical thymectomy for myasthenia gravis between 1992 and 1999. RESULTS: There were 24 men and 54 women. Mean age was 40 years (range, 13 to 78 years). Twelve patients were in Osserman class 1, 25 in class 2, 30 in class 3, and 11 in class 4 (mean, 2.5). There was no perioperative mortality and 6 (7.7%) morbidities. Mean length of stay was 1.5 days and mean follow-up, 54.6 months. The crude cumulative complete remission (asymptomatic off medications for 6 months) rate was 39.7% (n = 31). Only 8 patients (10.3%) failed to improve after transcervical thymectomy. Kaplan-Meier estimates of complete remission were 31% and 43% at 2 and 5 years, respectively. Eight patients with thymoma had a 5-year estimated complete remission rate of 75% in contrast to 43% in 38 patients with thymic hyperplasia and 36% in 32 patients with neither thymoma nor hyperplasia (p = 0.01). Twelve patients with ocular myasthenia had a 5-year estimated complete remission rate of 57%, whereas patients with mild-to-moderate (n = 55) or severe (n = 11) generalized symptoms had 5-year complete remission rates of 43% and 30%, respectively (p = 0.21). CONCLUSIONS: Overall, extended transcervical thymectomy offers results that are comparable to those published for the transsternal procedure. Patients with milder disease (including isolated ocular disease) and taking no preoperative immunosuppressive agents appear to experience higher remission rates. In contrast to previous studies, we also find that small thymomas predict better responses to thymectomy.

Adolescent↗
PubMed2002

Malignant mesothelioma: options for management.

In the past, there has been a tendency to think of diffuse malignant pleural mesothelioma as one disease in therapeutic terms, regardless of histological type and tumor stage. This does not happen with other tumors, yet it is equally illogical and inappropriate in mesothelioma. As with other tumors, early diagnosis-while the disease is still in stage I, or even at an in situ stage-must be the goal so that therapy can be maximized, particularly if immunotherapy or gene therapy is to be used. Patients with pure epithelial mesothelioma have a better prognosis and respond better to trimodality therapy. Stage I patients who meet fitness criteria should be offered the option of radical surgery in combination with chemotherapy and radiotherapy. Further research is required to determine the optimum neoadjuvant and adjuvant modalities, particularly the timing of individual drugs, use of hyperthermia, and route of administration. The place of immunotherapy and gene therapy as adjunctive treatments also remains to be defined. For example, it may be possible to reduce tumor bulk and perhaps downstage the disease with immunotherapy before radical surgery, if treatment is started early enough. Gene therapy may have a role either preoperatively or in destroying the microscopic disease that remains after radical surgery. These and other combinations of treatment need to be tested in well-designed clinical trials, probably on a multicenter basis (to enroll a sufficient number of patients). Finding the means to improve treatment for sarcomatous and mixed histology mesothelioma remains a challenge. At present, radical surgery does not seem worthwhile for these patients when combined with currently employed chemotherapy and radiotherapy; however, chemotherapy combinations used for treating other sarcomas need to be evaluated as adjunctive therapy before radical surgery is abandoned altogether as a mode of treatment. A collaborative approach involving thoracic surgeons, basic scientists and oncologists, and physicians with experience in treating mesothelioma is essential. Despite its increasing frequency, mesothelioma is still a relatively rare tumor, so treatment should be concentrated in relatively few supraregional centers to maximize expertise and allow innovative treatment combinations to be implemented with the greatest chance of success. Evaluation of new therapeutic approaches will be achieved more rapidly if these supraregional centers collaborate in multicenter trials. The nihilistic approach of simply waiting until the mesothelioma epidemic eventually begins to decline spontaneously in 20 or 30 years is untenable in view of the hundreds of thousands of deaths that will result if no effective treatment is found.

Humans↗
PubMed2002

Management of unremitting chylothorax by percutaneous embolization and blockage of retroperitoneal lymphatic vessels in 42 patients.

PURPOSE: To demonstrate the applicability, technique, and efficacy of percutaneous transabdominal catheter embolization or needle disruption of retroperitoneal lymphatic vessels in the treatment of high-output or unremitting chylothorax. MATERIALS AND METHODS: Forty-two patients (21 men, 21 women; mean age, 56 y; range, 19-80 y) who had chylothorax with various etiologies were referred from the thoracic surgery department for treatment as soon as chylothorax was documented. The thoracic duct was punctured and catheterized via a peritoneal cannula to facilitate embolization with use of microcoils, particles, or glue; if there were no lymph trunks that could be catheterized, attempts were made to disrupt lymph collaterals with use of needles. RESULTS: The thoracic duct was catheterized in 29 patients and embolized in 26 patients. In patients with lymph trunks that could be catheterized, treatment resulted in cure within 7 days in 16 patients and partial response with cure within 3 weeks in six patients. In the patients with lymph trunks that could not be catheterized (n = 16), disruption with use of needles resulted in cure in five patients and partial response in two patients. Cure and partial response rates after thoracic duct embolization and needle disruption were 73.8%, with no morbidity. Surgical thoracic duct ligation was performed in seven patients. The nonprocedural mortality rate was 19%. Follow-up was 3 months or longer. CONCLUSIONS: Effective percutaneous treatment of high-output or medically uncontrollable chylothorax was performed promptly and safely in more than 70% of referred cases. This procedure should be attempted, especially if patients are very ill, before riskier surgical thoracic duct ligation is considered.

Adult↗
PubMed2002

Cardiopulmonary bypass for bilateral sequential lung transplantation in patients with chronic obstructive pulmonary disease without adverse effect on lung function or clinical outcome.

OBJECTIVE: The use of cardiopulmonary bypass in lung transplantation remains controversial. Previous studies have concluded that cardiopulmonary bypass is deleterious, but these studies were confounded by the inclusion of patients with different diagnoses undergoing single- and double-lung transplantation with elective or emergency use of bypass. The goal of this study was to determine whether cardiopulmonary bypass has deleterious effects on lung function or clinical outcome by analyzing the cases of patients with a single disease entity and elective use of bypass for bilateral sequential lung transplantation. METHODS: A retrospective review of 50 patients with chronic obstructive pulmonary disease who underwent bilateral sequential lung transplantation was performed. Fourteen patients who underwent elective cardiopulmonary bypass for 218.3 +/- 75.4 minutes were compared to 36 control patients. RESULTS: After the operation, the bypass and nonbypass groups were not significantly different with respect to median duration of mechanical ventilation (1 day vs 1 day, P =.76), median stay in the intensive care unit (4 days vs 4 days, P =.44), median hospital stay (15.5 days vs 16 days, P =.74), mean increase in serum creatinine level (1.4 +/- 1.9 mg/dL vs 0.9 +/- 1.0 mg/dL, P =.33), and mean ratio of Pao(2) to fraction of inspired oxygen at 1 hour (376.6 +/- 123 vs 357.0 +/- 218, P =.75), at 24 hours (309.9 +/- 92 vs 350.6 +/- 122, P =.26), and at 48 hours (335.0 +/- 144 vs 316.2 +/- 120, P =.64). Late outcome markers compared between the bypass and nonbypass groups were the following: 1-year percentage predicted forced expiratory volume in 1 second (76.1% +/- 17.0% vs 85.3% +/- 21.7%, P =.24), 30-day mortality (7.1% vs 8.3%, P >.999), 1-year survival (85.7% vs 80.1%, P =.66), 3-year survival (64.3% vs 58.3%, P =.70), and the prevalence of bronchiolitis obliterans syndrome (0% vs 36.1%, P =.01). CONCLUSION: Cardiopulmonary bypass appears to have no deleterious effect on early lung function or clinical outcome. We hope that this pilot study removes some of the unwarranted fear of the use of bypass in lung transplantation for chronic obstructive pulmonary disease.

Analysis of Variance↗
PubMed2002

Long-term pain and activity during recovery from major thoracotomy using thoracic epidural analgesia.

BACKGROUND: Pain following thoracotomy can persist for years with an undetermined impact on quality of life. Factors hypothesized to modulate this painful experience include analgesic regimen, gender, and type of incision. METHODS: A total of 157 generally healthy patients of both genders scheduled for segmentectomy, lobectomy, or bilobectomy through a posterolateral or muscle-sparing incision were randomly assigned to receive thoracic epidural analgesia initiated prior to incision or at the time of rib approximation. Pain and activity scores were obtained 4, 8, 12, 24, 36, and 48 weeks after surgery. RESULTS: Overall, there were no differences in pain scores between the control and intervention groups during hospitalization (P >or= 0.165) or after discharge (P>or= 0.098). The number of patients reporting pain 1 yr following surgery (18 of 85; 21.2%) was not significantly different (P = 0.122) from the number reporting preoperative pain (15 of 120; 12.5%). During hospitalization, women reported greater pain than men (worst pain, P= 0.007; average pain, P= 0.016). Women experienced fewer supraventricular tachydysrhythmias (P = 0.013) and were thus discharged earlier (P = 0.002). After discharge women continued to report greater discomfort than men (P <or= 0.016), but did not differ from men in their level of physical activity (P = 0.241). CONCLUSIONS: Initiation of thoracic epidural analgesia prior to incision or the use of a muscle-sparing incision did not significantly impact pain or physical activity. Although women reported significantly greater pain during hospitalization and after discharge, they experienced fewer complications, were more likely to be discharged from the hospital sooner, and were just as active after discharge as men.

Adult↗