In Vitro Fertilization Practice in Patients with Absolute Uterine Factor Undergoing Uterus Transplant in the United States.

OBJECTIVE: Report detailed, pooled multicenter experiences and outcomes after IVF among patients undergoing uterus transplantation in the United States. DESIGN: Cohort study SUBJECTS: Patients undergoing uterus transplant from the three longest running uterus transplant clinical trials in the United States. INTERVENTION: In vitro fertilization among uterus transplant patients MAIN OUTCOME MEASURES: Reproductive outcomes pre- and post-transplant ovarian stimulation RESULTS: 31 uterus transplant recipients were included in this cohort (mean age at transplant was 31 years, standard deviation 4.7). Prior to transplant, recipients completed a mean of 2 oocyte retrievals (range 1-4), banking a mean of 8 untested embryos (range 3-24) or 6 euploid embryos (range 2-10). Post-transplant retrieval cycles were required in 19% of recipients (n=6/31): a total of 16 cycles (range 2-4 cycles per recipient). All post-transplant retrievals were performed vaginally without complication. Preimplantation genetic testing was used by 74% of subjects (n=23/31). 72 autologous single embryo transfers occurred in 23 patients who completed at least one embryo transfer. Two embryo transfers followed a fresh IVF cycle and the remainder were frozen embryo transfers (n=70). Endometrial preparation during was more commonly performed with programmed protocols (n=61) (exogenous administration of estrogen/progesterone) compared to natural cycle protocols (n=9). The overall live birth rate for this cohort was 35% (n=25/72) per embryo transfer. Among those patients who had an embryo transfer leading to a live birth (n=21), a mean of 2.2 embryo transfers was performed. The overall live birth rate after the first embryo transfer was 57% (n=13/23) and rose to 74% after a second embryo transfer (n=17/23). There was no difference in rate of preeclampsia, live birth, neonatal birth, or placental weights among programmed versus natural cycle frozen embryo transfers. There were no differences in the live birth rate between living or deceased donor uteri (37% versus 32%, p=0.6). CONCLUSIONS: Post-transplant ovarian stimulation was required in 26% (n=6/23) of recipients undergoing at least one embryo transfer despite high rates of preimplantation genetic testing and pre-transplant embryo cryopreservation. Post-transplant retrievals were performed transvaginally, without complication. Future reporting of IVF experience will be essential to optimize reproductive outcomes after uterus transplant.

Field Evaluation of Indoor Thermal Fog and Ultra-Low Volume Applications For Control of Aedes aegypti in Thailand.

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.

Examination of the physical properties of Microcystis aeruginosa flocs produced on coagulation with metal salts.

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.

Phase II study of neoadjuvant therapy with docetaxel, cisplatin, panitumumab, and radiation therapy followed by surgery in patients with locally advanced adenocarcinoma of the distal esophagus (ACOSOG Z4051).

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.

Incidence, causes and outcomes of lameness cases in a working military horse population: a field study.

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.

Early ghrelin treatment attenuates disruption of the blood brain barrier and apoptosis after traumatic brain injury through a UCP-2 mechanism.

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.

Long-segment, supercharged, pedicled jejunal flap for total esophageal reconstruction.

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.

Postoperative radiotherapy increases locoregional control of patients with stage IIIA non-small-cell lung cancer treated with induction chemotherapy followed by surgery.

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.

Induction treatment before surgery for non-small cell lung cancer.

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.

Resection of advanced thoracic malignancies requiring cardiopulmonary bypass.

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.

Human Rad17 is phosphorylated upon DNA damage and also overexpressed in primary non-small cell lung cancer tissues.

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.

Experience with the chin tuck maneuver in postesophagectomy aspirators.

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.

Cationic liposome-mediated E1A gene transfer to human breast and ovarian cancer cells and its biologic effects: a phase I clinical trial.

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.

A three-step strategy of induction chemotherapy then chemoradiation followed by surgery in patients with potentially resectable carcinoma of the esophagus or gastroesophageal junction.

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

Preoperative chemotherapy for lung cancer does not increase surgical morbidity.

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

Pilot study of concurrent 5-fluorouracil/paclitaxel plus radiotherapy in patients with carcinoma of the esophagus and gastroesophageal junction.

Preoperative concurrent chemotherapy and radiotherapy can be highly effective but are often associated with significant rates of morbidity and even mortality. We studied the toxicity of continuous infusion of 5-fluorouracil (5-FU) and weekly paclitaxel combined with radiotherapy. Patients had histologic proof of local-regional carcinoma of the esophagus or gastroesophageal (GE) junction, a Karnofsky performance status of 70 or greater, and normal liver, renal, and bone marrow functions. Chemotherapy consisted of continuous infusion of 5-FU (300 mg/m2/d) for 5 days a week for 5 weeks, plus paclitaxel (45 mg/m2) given during 3 hours every week for 5 weeks. Based on the tumor location and its resectability, the total dose of concurrent radiation varied between 45 Gy and 50.4 Gy. Nine men and one woman, with a median age of 61 years, were evaluated. One had GE junction cancer, six had distal esophageal cancer, and three had midesophageal cancer. Weight loss, nausea, vomiting, and dysphagia of grades I and II were noted. The hematologic toxicity was mild. No patients required transfusion. There was no leukopenia or thrombocytopenia. None of the patients was hospitalized during chemoradiation; all patients completed treatment as outpatients. Five patients had subsequent surgical resections: one had a pathologically complete response, and two had a partial response (>90% necrosis). Continuous infusion of 5-FU plus paclitaxel given concurrently with radiotherapy was well tolerated. We plan to study this regimen further in upper gastrointestinal cancers.