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1.
Fertil Steril ; 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38631504

ABSTRACT

OBJECTIVE: To report detailed, pooled multicenter experiences and outcomes after in vitro fertilization (IVF) treatment among patients undergoing uterus transplantation (UTx) in the US. DESIGN: Cohort study. SETTING: Hospital. PATIENTS: Patients undergoing UTxsfrom the three longest-running UTx clinical trials in the US. INTERVENTION: In vitro fertilization treatment among patients undergoing UTx.. MAIN OUTCOME MEASURES: Reproductive outcomes pretransplant and posttransplant ovarian stimulation. RESULTS: Thirty-one uterus transplant recipients were included in this cohort (mean [±SD] age at transplant was 31 ± 4.7 years). Before transplant, recipients completed a mean of two oocyte retrievals (range 1-4), banking a mean of eight untested embryos (range 3-24) or six euploid embryos (range 2-10). Posttransplant retrieval cycles were required in 19% (n = 6/31) of recipients, for a total of 16 cycles (range 2-4 cycles per recipient). All posttransplant retrievals were performed vaginally without complications. Preimplantation genetic testing was used by 74% (n = 23/31) of subjects. Seventy-two autologous single embryo transfers (ETs) occurred in 23 patients who completed at least one ET. Two ETs followed a fresh IVF treatment cycle, and the remainder (n = 70) were frozen ETs. Endometrial preparation was more commonly performed with programmed protocols (n = 61) (exogenous administration of estrogen and progesterone) compared with natural cycle protocols (n = 9). The overall live birth rate (LBR) for this cohort was 35% (n = 25/72) per ET. Among those patients (n = 21) who had an ET leading to a live birth, a mean of 2.2 ETs were performed. The overall LBR after the first ET was 57% (n = 13/23) and rose to 74% (n = 17/23) after a second ET. There was no difference in rate of preeclampsia, live birth, neonatal birth, or placental weights among programmed vs. natural cycle frozen ETs. There were no differences in the LBR between living or deceased donor uteri (37% vs. 32%). CONCLUSIONS: Posttransplant ovarian stimulation was required in 26% (n = 6/23) of recipients undergoing at least one ET, despite high rates of preimplantation genetic testing and pretransplant embryo cryopreservation. Posttransplant retrievals were performed transvaginally, without complications. Future reporting of IVF treatment experiences will be essential to optimizing reproductive outcomes after a uterus transplant. CLINICAL TRIAL REGISTRATION NUMBERS: NCT02656550 (Baylor University Medical Center); NCT03307356 (University of Pennsylvania); and NCT02573415 (Cleveland Clinic).

3.
J Am Mosq Control Assoc ; 33(2): 116-127, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28590217

ABSTRACT

Efficacies of a handheld thermal fogger (Patriot™) and a backpack ultra-low volume (ULV) sprayer (Twister™) with combinations of 2 different adulticides (pyrethrin, deltamethrin) and an insect growth regulator (pyriproxyfen) were field-tested and compared for their impact on reducing indoor Aedes aegypti populations in Thailand. The effectiveness of the indoor space sprays was evaluated by sampling the natural Ae. aegypti population in houses and determining their physiological status, by monitoring mortality of sentinel caged mosquitoes (AFRIMS strain) and by assessing larval mortality in laboratory bioassays using water exposed to the spray. A total of 14,742 Ae. aegypti were collected from Biogents Sentinel traps in this study. The combination of ULD® BP-300 (3% pyrethrin) and NyGuard® (10% pyriproxyfen) sprayed either by the Patriot or Twister significantly reduced some Ae. aegypti populations up to 20 days postspray relative to the control clusters. The addition of pyriproxyfen to the adulticide extended how long household mosquito populations were suppressed. In 2 of the 4 products being compared, the Twister resulted in higher mortality of caged mosquitoes compared with the Patriot. However, neither machine was able to achieve high mortality among Ae. aegypti placed in hidden (protected) cages. The larval bioassay results demonstrated that the Twister ULV provided better adult emergence inhibition than the Patriot (thermal fogger), likely due to larger droplet size.


Subject(s)
Aedes , Insecticides , Juvenile Hormones , Mosquito Control , Nitriles , Pyrethrins , Pyridines , Animals , Thailand
4.
Water Res ; 60: 197-209, 2014 Sep 01.
Article in English | MEDLINE | ID: mdl-24859233

ABSTRACT

Coagulation-flocculation (C-F) is a key barrier to cyanobacterial and algal cell infiltration in water treatment plants during seasonal blooms. However, the resultant cell floc properties, in terms of size, strength and density, which dominate under different coagulation conditions and govern cell removal, are not well understood. This paper investigated the floc properties produced during C-F of the cyanobacterium, Microcystis aeruginosa, under low and high doses of aluminium sulphate and ferric chloride coagulants and at different pH values, so as to promote charge neutralisation (CN) and sweep flocculation (SF) dominant conditions (or a combination of these). It was demonstrated that application of ferric chloride produced larger flocs that resulted in higher cell removal during jar testing. These flocs were also larger than those observed for natural organic matter (NOM) and kaolin, suggesting a role of algogenic organic matter (AOM) as an inherent bioflocculant. Under SF conditions, stronger flocs were produced; however, these had lower capacity for size recovery after exposure to high shear. Analysis of particle size distribution demonstrated that large scale fragmentation followed by erosion dominated for CN while erosion dominated under SF conditions. Overall, marked differences were observed dependent on the coagulation regime imposed that have implications for improving robustness of cell removal by downstream separation processes. While the cyanobacterium, M. aeruginosa, appeared to share general floc characteristics commonly observed for NOM and kaolin flocs, there were distinct differences in terms of size and strength, which may be attributed to AOM.


Subject(s)
Alum Compounds/chemistry , Chlorides/chemistry , Ferric Compounds/chemistry , Microcystis/metabolism , Water Purification , Alum Compounds/metabolism , Chlorides/metabolism , Ferric Compounds/metabolism , Flocculation , Hydrogen-Ion Concentration , Particle Size
5.
Ann Oncol ; 25(5): 1039-44, 2014 May.
Article in English | MEDLINE | ID: mdl-24562448

ABSTRACT

BACKGROUND: Preoperative chemoradiotherapy (CRT) improves outcomes in patients with locally advanced but resectable adenocarcinoma of the esophagus. ACOSOG Z4051 evaluated CRT with docetaxel, cisplatin, and panitumumab (DCP) in this patient group with a primary end point of a pathologic complete response (pCR) ≥35%. PATIENTS AND METHODS: From 15 January 2009 to 22 July 2011, 70 patients with locally advanced but resectable distal esophageal adenocarcinoma were enrolled. Patients received docetaxel (40 mg/m(2)), cisplatin (40 mg/m(2)), and panitumumab (6 mg/kg) on weeks 1, 3, 5, 7, and 9 with RT (5040 cGy, 180 cGy/day × 28 days) beginning week 5. Resection was planned after completing CRT. PCR was defined as no viable residual tumor cells. Secondary objectives included near-pCR (≤10% viable cancer cells), toxicity, and overall and disease-free survival. Adverse events were graded using the CTCAE Version 3.0. RESULTS: Five of 70 patients were ineligible. Of 65 eligible patients (59 M; median age 61), 11 did not undergo surgery, leaving 54 assessable. PCR rate was 33.3% and near-pCR was 20.4%. Secenty-three percent of patients completed DCP (n = 70) and 92% completed RT. 48.5% had toxicity ≥grade 4. Lymphopenia (43%) was most common. Operative mortality was 3.7%. Adult respiratory distress syndrome was encountered in two patients (3.7%). At median follow-up of 26.3 months, median overall survival was 19.4 months and 3-year overall survival was 38.6% (95% confidence interval 24.5% to 60.8%). CONCLUSIONS: Neoadjuvant CRT with DCP is active (pCR + near-pCR = 53.7%) but toxicity is significant. Further evaluation of this regimen in an unselected population is not recommended. CLINICALTRIALSGOV IDENTIFIER: NCT00757172.


Subject(s)
Adenocarcinoma/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Esophageal Neoplasms/therapy , Esophagogastric Junction/pathology , Adenocarcinoma/mortality , Adult , Aged , Antibodies, Monoclonal/administration & dosage , Chemoradiotherapy, Adjuvant , Cisplatin/administration & dosage , Disease-Free Survival , Docetaxel , Esophageal Neoplasms/mortality , Esophagogastric Junction/surgery , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoadjuvant Therapy , Panitumumab , Taxoids/administration & dosage , Treatment Outcome
6.
Equine Vet J ; 46(2): 194-7, 2014 Mar.
Article in English | MEDLINE | ID: mdl-23662972

ABSTRACT

REASONS FOR PERFORMING STUDY: Lameness is a common problem in the horse. Despite this, information on the incidence of lameness in horses in the UK is restricted to studies of lameness in performance horses, racehorses or referral hospital populations. OBJECTIVES: To determine the overall incidence and common causes of lameness in a working horse population and incidence, duration and outcome of conditions observed. STUDY DESIGN: Prospective questionnaire study. METHODS: Questionnaires were used to record lameness episodes in 294 horses in an equine military establishment. Information recorded included age, years of service, type of work, causal lesion, time taken to return to work and outcome. Lameness problems could be reported by any staff involved in the horses' care and were diagnosed by a veterinary surgeon or qualified farrier. Trends between lame and nonlame populations were compared using Chi-square analysis. Lameness diagnoses were grouped and analysed by disease category. RESULTS: Completed questionnaires for 273 horses were analysed. The mean monthly incidence of lameness was 2.1%, equivalent to an annual rate of 25.4 cases per 100 horses per annum, with a mean of 1.2 lameness episodes per horse in the lame population. Horse age and duration of service were not significantly different between lame and nonlame populations. The most common diagnoses were cellulitis (18.6%), skin wounds (16.3%) and foot/shoeing problems (11.6%) and 88% of cases had returned to previous levels of work by the conclusion of the study. CONCLUSIONS: This initial field study showed that lameness is a common occurrence in this working military horse population and the majority of cases make a full return to work. The most common causes of lameness identified in this study and outcomes of these conditions differ from existing literature. POTENTIAL RELEVANCE: This study highlights the need for further studies of lameness in the wider horse population.


Subject(s)
Horse Diseases/etiology , Lameness, Animal/etiology , Animals , Data Collection , Horses , Surveys and Questionnaires
7.
Brain Res ; 1489: 140-8, 2012 Dec 13.
Article in English | MEDLINE | ID: mdl-23099053

ABSTRACT

Ghrelin has been shown to be anti-inflammatory and neuroprotective in models of neurologic injury. We hypothesize that treatment with ghrelin will attenuate breakdown of the blood brain barrier (BBB) and apoptosis 24h following traumatic brain injury (TBI). We believe this protection is at least in part mediated by up-regulation of UCP-2, thereby stabilizing mitochondria and preventing up-regulation of caspase-3. A weight drop model was used to create severe TBI. Balb/c mice were divided into 3 groups. Sham: no TBI or ghrelin treatment; TBI: TBI only; TBI/ghrelin: 20µg (IP) ghrelin at the time of TBI. BBB permeability to 70kDa FITC-Dextran was measured 24h following injury and quantified in arbitrary integrated fluorescence (afu). Brain tissue was subjected to TUNEL staining and TUNEL positive cells were quantified. Immunohistochemistry was performed on injured tissue to reveal patterns of caspase-3 and UCP-2 expression. TBI increased cerebral vascular permeability by three-fold compared to sham. Ghrelin treatment restored vascular permeability to the level of shams. TUNEL staining showed that ghrelin mitigated the significant increase in apoptosis that follows TBI. TBI increased both caspase-3 compared to sham. Treatment with ghrelin significantly increased UCP-2 compared to TBI alone and this increase in UCP-2 expression was associated with a decrease in expression of caspase-3. Early ghrelin treatment prevents TBI induced BBB disruption and TBI mediated apoptosis 24h following injury. These results demonstrate the neuroprotective potential of ghrelin as a therapy in TBI.


Subject(s)
Apoptosis/drug effects , Blood-Brain Barrier/drug effects , Brain Injuries/drug therapy , Ghrelin/pharmacology , Ion Channels/metabolism , Mitochondrial Proteins/metabolism , Animals , Apoptosis/physiology , Blood-Brain Barrier/physiology , Brain Injuries/metabolism , Brain Injuries/pathology , Capillary Permeability/drug effects , Capillary Permeability/physiology , Caspase 3/metabolism , Disease Models, Animal , Ghrelin/metabolism , Male , Mice , Mice, Inbred BALB C , Mitochondria/drug effects , Mitochondria/metabolism , Neuroprotective Agents/metabolism , Neuroprotective Agents/pharmacology , Uncoupling Protein 2
8.
J Thorac Cardiovasc Surg ; 130(5): 1391-8, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16256794

ABSTRACT

OBJECTIVE: Many patients with cancer have limited esophageal reconstruction options when the stomach is unavailable as a replacement conduit or when long-segment discontinuity exists. Jejunum has been used as an alternative conduit, both as a pedicled or free flap interposition; however, reports of this are usually limited to short-segment repairs. Microvascular augmentation of a pedicled jejunal flap allows creation of a longer conduit, making it possible to replace the entire esophagus with jejunum. Few reports describe this technique in patients with cancer. We report our initial experience with "supercharged" pedicled jejunum as an alternative conduit for total esophageal reconstruction. METHODS: Review of a prospectively collected departmental database was performed to identify those patients who underwent total esophageal reconstruction with supercharged pedicled jejunum. Data regarding their perioperative course and postoperative function were gathered from the prospectively collected clinical data, review of hospital records, and patient interviews. RESULTS: Total esophageal reconstruction with supercharged pedicled jejunum was attempted in 26 patients (age range, 37-74 years) between March 2000 and April 2004. Twenty-four of 26 patients were ultimately discharged with an intact supercharged pedicled jejunum flap, for an overall success rate of 92.3%. One patient experienced intraoperative flap loss caused by technical difficulties harvesting the flap and never had the flap interposed. One other flap loss occurred in the early postoperative period in a patient who had multisystem organ failure after a prolonged reconstruction. Cervical anastomotic leaks occurred in 19.2% (5/26) of the patients. Two midconduit leaks occurred that were suspicious for iatrogenic perforation from nasogastric tube placement; one required reoperation. One additional early reoperation was performed for cecal ischemia. There were no mortalities. Functional results were available in 95.4% (21/22) of the patients receiving supercharged pedicled jejunum who survived at least 6 months after reconstruction. At the time of follow-up, 95% (20/21) of the patients were tolerating regular diet, and 76.2% (16/21) did not require any supplemental alimentation. Ninety-five percent (20/21) of the patients were free from reflux symptoms, and 80.9% (17/21) had no dumping symptoms. Only 1 patient required dilation of a midconduit stricture. One patient required late reoperation for conduit redundancy. CONCLUSIONS: Supercharged pedicled jejunum is a suitable alternative conduit for total esophageal replacement in patients with cancer with otherwise limited reconstructive options. Functional outcomes are excellent, despite the severity of disease and technical challenges in this patient population.


Subject(s)
Esophageal Neoplasms/surgery , Esophagus/surgery , Jejunum/transplantation , Surgical Flaps , Adult , Aged , Digestive System Surgical Procedures/methods , Humans , Middle Aged , Postoperative Complications/epidemiology , Prospective Studies
10.
Int J Radiat Oncol Biol Phys ; 56(3): 616-25, 2003 Jul 01.
Article in English | MEDLINE | ID: mdl-12788166

ABSTRACT

PURPOSE: To determine the effectiveness of postoperative radiotherapy (RT) in patients with Stage IIB and Stage IIIA non-small-cell lung cancer (NSCLC) treated with induction chemotherapy followed by surgery. METHODS AND MATERIALS: We retrospectively reviewed the treatment records of 98 patients (58 men and 40 women; median age 61 years, range 31-91) with Stage IIB and Stage IIIA NSCLC who were treated with induction chemotherapy followed by surgery at our institution between January 1990 and December 2000. Patients were grouped by treatment (chemotherapy/surgery alone vs. chemotherapy/surgery/RT), by disease stage and nodal classification. The rates of local control (LC), disease-specific survival, disease-free survival, and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS: Of the 98 patients, 40 had Stage IIB and 58 had Stage IIIA. The clinical disease stage and N stage were significantly greater in those patients who underwent RT than in those who did not; however, no statistically significant differences were identified in the additional characteristics between those receiving and not receiving RT within each stage or nodal group. The overall 5-year actuarial LC rate was 81% in the RT group and 54% in the chemotherapy/surgery-alone group (p = 0.07). Postoperative RT significantly improved the 5-year LC rate in patients with Stage IIIA disease (from 35% to 82%, p = 0.01). Postoperative RT did not significantly improve the 5-year OS rate (30% with RT vs. 49% without) for all patients or for patients with Stage IIIA disease. The disease-specific survival and disease-free survival rates did not differ between the treatment groups. Patients who responded to induction chemotherapy had a significantly greater 5-year OS rate (49%) than did those with stable or progressive disease (22%, p = 0.003). CONCLUSION: Postoperative RT in patients with Stage IIIA NSCLC treated with induction chemotherapy followed by surgery significantly improved LC without improving OS. Significantly improved survival was observed in all patients who responded to induction chemotherapy compared with those with stable or progressive disease.


Subject(s)
Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Neoplasms/radiotherapy , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/radiotherapy , Adult , Aged , Aged, 80 and over , Carcinoma, Large Cell/mortality , Carcinoma, Large Cell/pathology , Carcinoma, Large Cell/radiotherapy , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/radiotherapy , Chemotherapy, Adjuvant , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Radiotherapy Dosage , Remission Induction , Retrospective Studies , Survival Analysis
11.
Lung Cancer ; 42 Suppl 1: S9-14, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14708516

ABSTRACT

Surgery alone is currently still accepted "standard of care" for patients with operable NSCLC, this includes stages IA and IIB, as well as selected early subsets of IIIA disease. In more advanced and inoperable stage III disease, combinations of chemotherapy and radiotherapy remain the standard treatment approach for patients with good performance status. The role of surgery following induction therapy in these advanced stage III patients is at the moment not conclusively defined. More evidence from randomized trials is clearly needed to tailor treatment for the large number of patients that present in these locally advanced stages. Enrollment of patients into ongoing prospective clinical trials should be encouraged, whenever possible, to further define prognostic factors and improve multimodality strategies in this clinical setting.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/surgery , Lung Neoplasms/drug therapy , Lung Neoplasms/surgery , Carcinoma, Non-Small-Cell Lung/pathology , Drug Administration Schedule , Humans , Lung Neoplasms/pathology , Neoadjuvant Therapy , Neoplasm Staging , Prognosis , Randomized Controlled Trials as Topic
12.
Eur J Cardiothorac Surg ; 22(1): 47-52, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12103372

ABSTRACT

OBJECTIVES: Patients with malignancies involving cardiac structures have limited therapeutic options and significant risk of mortality. The decision to offer radical palliative or curative resection must be made only after consideration of the substantial surgical risks. The purpose of this retrospective study was to determine the feasibility and benefits of resection with cardiopulmonary bypass (CPB) of metastatic or non-cardiac primary malignancies extending directly into or metastasizing to the heart in select patients. Our results were examined to assess the risks and benefits of such radical therapy. METHODS: We retrospectively reviewed patient charts and identified all patients with malignancies involving the cardiac chamber or great vessels (excluding renal carcinomas with caval extension) or with substantial cardiac compression who had undergone resection with CPB at The University of Texas M.D. Anderson Cancer Center between January 1995 and July 2000. We evaluated demographic data, symptomatology, tumor characteristics, and outcomes. RESULTS: Nineteen patients (six males and 13 females; median age of patients, 47 years; age range, 17-67 years) were included in the study. Eleven patients underwent surgery with curative intent, and eight underwent surgery with palliative intent. Seventeen patients had tumors that required CPB because their tumors directly involved the heart and/or great vessels (nine sarcomas, seven epithelial carcinomas, and one unclassified), and two patients (both with sarcomas) required CPB to relieve tumor tamponade. The technique included CPB (n=5), CPB with diastolic arrest (n=12), and CPB with hypothermic circulatory arrest (n=2). Five patients underwent concomitant pneumonectomy, and three underwent lobectomy. Two patients (11%) died in the hospital after resection with palliative intent. Of the 11 patients who underwent resection with curative intent, ten (91%) had complete resections. The median time in the intensive care unit was 5.3 days (range, 0-37 days) and the median length of hospital stay was 17.2 days (range, 0-107 days). Major complications occurred in 11 patients (58%); the most common major complications were pneumonia (n=7 patients), mediastinal hematoma (n=4 patients), and acute respiratory distress syndrome (n=2 patients). The median follow-up duration was 27 months. The overall 1- and 2-year survival rates were 65 and 45%, respectively. CONCLUSIONS: Extensive thoracic tumors involving cardiac structures can be resected with acceptable risk. When resection was performed with curative intent, excellent 1- and 2-year cumulative survival rates were achieved. Although resection with palliative intent was associated with greater mortality rates, some patients survived for 1 and 2 years. The use of CPB in selected patients with thoracic malignancies should be considered, especially when complete resection can be achieved.


Subject(s)
Cardiac Surgical Procedures , Cardiopulmonary Bypass , Heart Neoplasms/surgery , Adolescent , Adult , Aged , Feasibility Studies , Female , Heart Arrest, Induced , Heart Neoplasms/mortality , Heart Neoplasms/secondary , Humans , Male , Middle Aged , Postoperative Complications , Pulmonary Artery , Retrospective Studies , Vascular Neoplasms/surgery
14.
Cancer Res ; 61(20): 7417-21, 2001 Oct 15.
Article in English | MEDLINE | ID: mdl-11606373

ABSTRACT

The spRAD17 gene is an essential component of the DNA damage and replication checkpoints in the fission yeast Schizosaccharomyces pombe. Cloning of the human homologue of spRAD17, hRAD17, indicated that it exhibits structural similarity with the replication accessory protein family, which include subunits of the Replication factor C complex. We have analyzed the phosphorylation status of hRad17 in response to DNA damaging agents. Our results showed that phosphorylation of hRad17 occurred immediately after UV and ionizing radiation treatment and reached peak level at approximately 3 h, suggesting that hRad17 may be a component of the DNA damage checkpoint. When primary tumor samples were analyzed, we observed that the majority (74%) of non-small cell lung carcinoma samples exhibited a significantly higher level of hRad17 expression compared with matched normal tissue controls. In contrast, hRad17 protein levels in a panel of primary colon carcinoma samples did not show an elevated level of expression compared with normal colon tissues. This observation suggests that the function of the hRAD17 gene may be involved in lung cancer development and may serve as a potential tumor marker.


Subject(s)
Carcinoma, Non-Small-Cell Lung/metabolism , Cell Cycle Proteins/metabolism , DNA Damage/physiology , Lung Neoplasms/metabolism , Carcinoma, Non-Small-Cell Lung/genetics , Cell Cycle Proteins/biosynthesis , Cell Cycle Proteins/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Humans , Lung Neoplasms/genetics , Phosphorylation , Tumor Cells, Cultured
15.
J Clin Oncol ; 19(14): 3422-33, 2001 Jul 15.
Article in English | MEDLINE | ID: mdl-11454891

ABSTRACT

PURPOSE: Preclinical studies have demonstrated that the adenovirus type 5 E1A gene is associated with antitumor activities by transcriptional repression of HER-2/neu and induction of apoptosis. Indeed, E1A gene therapy is known to induce regression of HER-2/neu-overexpressing breast and ovarian cancers in nude mice. Therefore, we evaluated the feasibility of intracavitary injection of E1A gene complexed with DC-Chol cationic liposome (DCC-E1A) in patients with both HER-2/neu-overexpressing and low HER-2/neu-expressing breast and ovarian cancers in a phase I clinical trial. PATIENTS AND METHODS: An E1A gene complexed with DCC-E1A cationic liposome was injected once a week into the thoracic or peritoneal cavity of 18 patients with advanced cancer of the breast (n = 6) or ovary (n = 12). RESULTS: E1A gene expression in tumor cells was detected by immunohistochemical staining and reverse transcriptase-polymerase chain reaction. This E1A gene expression was accompanied by HER-2/neu downregulation, increased apoptosis, and reduced proliferation. The most common treatment-related toxicities were fever, nausea, vomiting, and/or discomfort at the injection sites. CONCLUSION: These results argue for the feasibility of intracavitary DCC-E1A administration, provide a clear proof of preclinical concept, and warrant phase II trials to determine the antitumor activity of the E1A gene.


Subject(s)
Adenovirus E1A Proteins/genetics , Breast Neoplasms/therapy , Gene Transfer, Horizontal , Genetic Therapy , Ovarian Neoplasms/therapy , Adult , Aged , Apoptosis , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cholesterol/analogs & derivatives , Cytokines/metabolism , Female , Gene Expression , Genes, erbB-2 , Humans , Immunohistochemistry , In Situ Nick-End Labeling , Injections , Ki-67 Antigen , Liposomes , Middle Aged , Ovarian Neoplasms/genetics , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Peritoneal Cavity , Reverse Transcriptase Polymerase Chain Reaction , Thorax , Tumor Cells, Cultured
16.
Dysphagia ; 16(3): 216-9, 2001.
Article in English | MEDLINE | ID: mdl-11453570

ABSTRACT

Aspiration is a common finding in the postesophagectomy barium swallow that often necessitates premature termination of the study prior to complete evaluation of the gastric conduit. More importantly, aspiration may play a significant role in the high incidence of postoperative pulmonary complications in this population. The chin tuck maneuver is a postural technique that reduces and often eliminates aspiration in swallowing-impaired patients. To evaluate the ability of the chin tuck maneuver to prevent aspiration during radiographic examination of the gastric conduit, the technique was used in 21 esophagectomy patients who aspirated during a swallowing evaluation combining the barium swallow and videofluoroscopy. Aspiration was eliminated in 81% of aspirators using the chin tuck maneuver. The results of this study demonstrate that the chin tuck maneuver is a simple technique that should be attempted in patients who aspirate postesophagectomy during radiographic imaging studies that require multiple swallows of contrast materials. Combining the barium swallow with the videofluoroscopic evaluation of swallowing provides objective documentation of both the structural integrity of the gastric conduit and swallowing function in patients after esophagectomies who are at high risk for postoperative morbidity.


Subject(s)
Chin/physiology , Esophagectomy/methods , Movement/physiology , Pneumonia, Aspiration/therapy , Postoperative Complications , Posture , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged
17.
Cancer ; 92(2): 279-86, 2001 Jul 15.
Article in English | MEDLINE | ID: mdl-11466680

ABSTRACT

BACKGROUND: Patients with locoregional carcinoma of the esophagus or gastroesophageal junction have a poor survival rate after surgery. Preoperative chemotherapy or chemoradiotherapy has not improved the outcome for these patients. Our study was designed to assess the feasibility of preoperative induction combination chemotherapy in addition to chemoradiotherapy to improve the curative resection rate, local control, and survival. PATIENTS AND METHODS Patients having histologic proof of localized carcinoma (either squamous cell carcinoma or adenocarcinoma) of the esophagus or gastroesophageal junction underwent full classification including endoscopic ultrasonography (EUS). Patients first received up to two courses of induction chemotherapy consisting of 5-fluorouracil at 750 mg/m(2)/day as continuous infusion on Days 1--5, cisplatin at 15 mg/m(2)/day as an intravenous bolus on Days 1--5, and paclitaxel at 200 mg/m(2) as a 24-hour intravenous infusion on Day 1. The second course was repeated on Day 29. This was followed by radiotherapy (45 grays in 25 fractions) and concurrent admission of 5-fluorouracil (300 mg/m(2)/day as a continuous infusion 5 days/week) and cisplatin (20 mg/m(2) on Days 1--5 of radiotherapy). After chemoradiotherapy, patients underwent surgery. The feasibility of this approach, curative resection rates, patient survival, and patterns of failure were assessed. RESULTS: Thirty-seven of 38 patients enrolled were evaluable for toxicity and survival. Adenocarcinoma and distal esophageal location of carcinoma were observed frequently. Thirty-five (95%) of the 37 patients underwent surgery, all of whom had an R0 (curative) resection. A pathologic complete response was noted in 11 (30%) of the 37 total patients. In addition, 5 patients (14%) had only microscopic carcinoma. According to EUS classification, 31 (89%) of the 35 patients who underwent surgery had a T3 carcinoma whereas according to pathologic classification only 3 (9%) had a T3 carcinoma (P

Subject(s)
Adenocarcinoma , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell , Esophageal Neoplasms , Esophagogastric Junction/pathology , Stomach Neoplasms , Adenocarcinoma/drug therapy , Adenocarcinoma/radiotherapy , Adenocarcinoma/surgery , Adult , Aged , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/surgery , Cisplatin/administration & dosage , Combined Modality Therapy , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/radiotherapy , Esophageal Neoplasms/surgery , Esophagogastric Junction/surgery , Female , Fluorouracil/administration & dosage , Humans , Infusions, Intravenous , Injections, Intravenous , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Recurrence, Local , Paclitaxel/administration & dosage , Preoperative Care , Prognosis , Stomach Neoplasms/drug therapy , Stomach Neoplasms/radiotherapy , Stomach Neoplasms/surgery , Survival Analysis
19.
Ann Thorac Surg ; 71(4): 1105-11; discussion 1111-2, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11308144

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/therapy , Pneumonectomy/mortality , Vinblastine/analogs & derivatives , Aged , Carboplatin/administration & dosage , Cisplatin/administration & dosage , Etoposide/administration & dosage , Female , Follow-Up Studies , Humans , Male , Middle Aged , Multivariate Analysis , Pneumonectomy/methods , Postoperative Care , Premedication , Reference Values , Retrospective Studies , Survival Rate , Treatment Outcome , Vinblastine/administration & dosage , Vinorelbine
20.
Ann Thorac Surg ; 71(3): 962-6, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11269481

ABSTRACT

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.


Subject(s)
Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Small Cell/surgery , Lung Neoplasms/surgery , Neoplasms, Second Primary/surgery , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Small Cell/mortality , Female , Humans , Lung Neoplasms/mortality , Male , Middle Aged , Neoplasms, Second Primary/mortality , Survival Rate , Treatment Outcome
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