Is the risk of substantial LVSI in stage I endometrial cancer similar to PORTEC in the North American population? - A single-institution study.

OBJECTIVES: A pooled analysis of PORTEC-1 & 2 identified substantial lymphovascular space invasion (LVSI) in 4.8% of patients, which predicted for pelvic recurrence, distant metastasis, and overall survival. Our institution implemented the PORTEC three-tier system of LVSI reporting (absent, focal, or substantial). We aimed to quantify the incidence of substantial LVSI in a North American population and to correlate extent of LVSI with lymph node (LN) involvement. METHODS: A retrospective review was conducted on patients with clinically uterine-confined, endometrioid type endometrial cancer who underwent surgical staging and were found to have pT1a-b disease. Binary logistic regression was used to assess predictors of LN involvement (defined as ITC, micrometastases, or macrometastases). RESULTS: In total, 438 patients with pT1a-b disease were identified. In the overall cohort and in the subset meeting PORTEC-1 inclusion criteria (n = 195), no LVSI was present in 67.4% and 50.8%; focal LVSI was present in 16.7% and 24.1%; and substantial LVSI was present in 16.0% and 25.1%, respectively. Among patients who underwent surgical LN assessment (79.2%, n = 347), LNs were involved in 3.3% without LVSI, 7.5% with focal LVSI (OR 2.4), and 15.2% with substantial LVSI (OR 5.3) (p = .005), with a similar trend in the PORTEC-1 cohort. Extent of LVSI correlated with disease burden in LN metastases. CONCLUSION: Our incidence of substantial LVSI was three to five times higher than reported by PORTEC and correlated with LN involvement. This questions the reproducibility of the three-tier LVSI reporting system and emphasizes the need for multi-institutional data outside PORTEC for confirmation of our findings.

Surgical Outcomes of Patients Undergoing Extrafascial Hysterectomy After Neoadjuvant Radiotherapy With or Without Chemotherapy for Locally Advanced Endometrial Cancer Clinically Extending to the Cervix or Parametria.

OBJECTIVES: Recent data have shown high rates of clinical and pathologic responses to neoadjuvant radiation therapy for locally advanced endometrial cancer. There are limited data on the surgical outcomes of these patients in the era of modern radiation and surgical techniques. We sought to characterize surgical outcomes after extrafascial hysterectomy in this population. METHODS: Patients with endometrial cancer of all histologies clinically involving the cervix or parametria treated with neoadjuvant brachytherapy followed by extrafascial hysterectomy from 1999 to 2014 were identified. Patient charts were reviewed for data regarding treatment characteristics and postoperative outcomes. Pearson χ and logistic regression analyses were used to assess correlations between surgical complications and treatment-related variables. RESULTS: Twenty-nine patients met inclusion criteria. Mean operating time for the cohort was 115 minutes. Mean estimated blood loss was 100 mL. No visceral injuries occurred. Mean length of hospital stay was 1 and 4 days for the minimally invasive and laparotomy groups, respectively. Rates of postoperative ileus, blood transfusion, wound infection, and readmission were 3%, 3%, 6%, and 3%, respectively. No case of prolonged urodynamic dysfunction was noted. The rate of vaginal complications was significantly higher in the group of patients who underwent minimally invasive surgery as compared with laparotomy (33% vs 5%, P < 0.041). CONCLUSIONS: These data support adjuvant extrafascial hysterectomy after neoadjuvant radiotherapy for endometrial cancer with cervical or parametrial involvement as a safe and viable procedure, with low rates of postoperative complications. Extra care should be taken when closing the vaginal cuff to reduce the risk of vaginal cuff complications.

Moderate sedation for elective upper endoscopy with balanced propofol versus fentanyl and midazolam alone: a randomized clinical trial.

BACKGROUND AND STUDY AIMS: Balanced propofol sedation (BPS) combines propofol with opiates and benzodiazepines and targets at moderate sedation. Data comparing outcomes of BPS and standard sedation with opiates and benzodiazepines during elective esophagogastroduodenoscopy (EGD) are sparse. The primary end point of this study was to compare, in the recovery area, patient satisfaction with EGD following BPS versus standard sedation. PATIENTS AND METHODS: Prospective, single-blinded randomized trial in 110 outpatients undergoing elective EGD and randomized 1:1 to BPS or standard sedation. Upon full recovery, the primary outcome of patient satisfaction was assessed using a 100-mm visual analogue scale (VAS) (1 = not at all satisfied, 100 = completely satisfied). Sedation recovery times and recall of pain and gagging (1 = none, 100 = severe) were also evaluated using a VAS. RESULTS: The BPS and standard sedation groups were similar regarding American Society of Anesthesiologists (ASA), Mallampati class, age, sex, and body mass index (BMI). Compared with the standard sedation arm, the BPS group exhibited higher median procedural satisfaction (99 vs. 85, P < 0.001), and lower median scores for recall of pain (P < 0.001) and gagging (P < 0.001). BPS resulted in a shorter median recovery time (min) (11 vs. 23, P < 0.001). On multivariable regression analysis, predictors of patient satisfaction included use of propofol, increased age, and higher fentanyl dosage. CONCLUSIONS: BPS targeted to moderate sedation by adequately trained endoscopists results in superior patient satisfaction and shorter recovery times than standard sedation alone during EGD.

Is Substantial Lymphovascular Space Invasion Prognostic for Clinical Outcomes in Type II Endometrial Cancer?

AIMS: Substantial lymphovascular space invasion (LVSI) compared with none or focal LVSI is predictive of lymph node involvement and worse clinical outcomes in endometrioid-type endometrial carcinoma. We aimed to quantify the incidence of substantial LVSI in type II (clear cell and serous) endometrial cancer and correlate the extent of LVSI with clinical outcomes. MATERIALS AND METHODS: A retrospective review was conducted on type II endometrial cancer patients who underwent surgical management from July 2017 to December 2019 using the three-tier LVSI scoring system. Binary logistic regression and Cox regression were used to analyse predictors of lymph node involvement or survival outcomes, respectively. The Kaplan-Meier method and Log-rank test were used to analyse differences in locoregional disease-free survival (LR-DFS), distant metastasis disease-free survival (DM-DFS) and overall survival between patients with substantial versus none/focal LVSI. RESULTS: In 79 patients with type II endometrial carcinoma, no LVSI, focal LVSI and substantial LVSI was present in 48.1%, 15.2% and 36.7% of patients, respectively. Lymph nodes were involved in 0.0% with no LVSI, 20.0% with focal LVSI and 60.0% with substantial LVSI (P < 0.001). The median follow-up was 22.2 months. In patients with none/focal versus substantial LVSI, the 2-year LR-DFS and DM-DFS rates were 91.5% versus 71.4% (P = 0.01) and 90.2% versus 63.8% (P = 0.005), respectively. On univariate analysis, myometrial invasion ≥50%, tumour size ≥3.6 cm, substantial versus none/focal LVSI, lymph node involvement and omission of adjuvant radiotherapy were significant predictors for worse LR-DFS and DM-DFS (P < 0.05). DISCUSSION: Substantial LVSI has a high incidence in type II pathology at our institution and predicts for lymph node involvement and worse clinical outcomes.

Dural venous sinus thrombosis in anaplastic astrocytoma following concurrent temozolomide and focal brain radiotherapy plus bevacizumab.

Malignant gliomas have long been a therapeutic dilemma in neuro-oncology, with a poor overall prognosis. Standard treatment, consisting of primary resection, followed by radiation therapy and temozolomide, has improved prognosis. Recently, studies have looked at the addition of bevacizumab (Avastin), a humanized murine IgG1 monoclonal antibody against vascular endothelial growth factor-A, to conventional regiments. Bevacizumab gained US FDA approval for single agent use in recurrent glioblastoma in 2009. Known side effects of bevacizumab include increased risk of arterial and venous thromboembolism, as well as hemorrhage. With emerging data for the use of bevacizumab in malignant gliomas, the extent of risks such as bleeding and thrombosis in patients with primary brain tumors treated with bevacizumab remains unknown. Here, we present only the second reported case of dural venous sinus thrombosis during treatment with bevacizumab and the first reported case for a primary glioma treated with temozolomide, radiation, and bevacizumab.

Early outcomes after definitive chemoradiation therapy with Vienna/Venezia hybrid high-dose rate brachytherapy applicators for cervical cancer: A single-institution experience.

PURPOSE: The Vienna and Venezia (Elekta) are hybrid intracavitary/interstitial brachytherapy (BT) applicators for cervical cancers unsuitable for intracavitary BT alone to improve target coverage or reduce critical organ dose. There is limited outcome data with the use of these applicators outside published experience of the EMBRACE group. We report feasibility and early outcomes with the use of these hybrid applicators at our institution. METHODS AND MATERIALS: Hybrid applicators were used to treat 61 patients with cervical cancer from November 2011 to December 2019. Indications for hybrid applicator use were involvement of the vagina in 10 patients (16%), residual central or parametrial disease in 46 patients (75%), and a narrow introitus in 5 patients (9%). Toxicities were graded using the CTCAE v4.0. Outcomes were assessed with the Kaplan-Meier method. RESULTS: Median follow-up was 16 months (IQR 9-32 mos). Median HRCTV volume was 31.6 cm3 (IQR 25-48 cm3). Median HRCTV D90 was 86.1 Gy (IQR 84.3-88.0 Gy). In 54 patients with follow-up PET/CT at 3 months, complete initial imaging response locally was seen in 46 patients.Estimated 12-month Kaplan-Meier overall survival, locoregional control, distant control, and recurrence-free survival estimates were 86.9%, 80.6%, 73.8%, and 65.9%, respectively. The 12-month incidence of Grade 3+ GI/GU chronic toxicities was 5.7%, consisting of vesicovaginal fistula, rectovaginal fistula, and ureterovesical fistula. CONCLUSIONS: Our single-institution data support the use of the hybrid applicators, as an alternative to traditional BT applicators when clinically warranted. Use of hybrid applicators is feasible with adequate coverage of disease in the vagina and parametrium.

Regional Control and Chemoradiotherapy Dose Response for Clinically Involved Lymph Nodes in Patients with Locally Advanced Endometrial Cancers Who are Not Candidates for Upfront Surgical Staging Extrafascial Hysterectomy.

AIMS: There are limited data in endometrial cancer for nodal control and appropriate treatment volume for non-surgically resected nodes treated with chemoradiotherapy (CRT) for patients who are not candidates for upfront extrafascial hysterectomy. MATERIALS AND METHODS: Patients (n = 105) with clinical stage ≥ II endometrial cancer who were not candidates for upfront extrafascial hysterectomy treated with preoperative CRT were retrospectively reviewed. CRT included pelvic nodes to the common iliac for node-negative disease and para-aortic nodes to the renal vessel for any node-positive disease. Involved nodes most commonly received a boost of 55 Gy in 25 fractions ± additional 4-6 Gy sequential boost for nodes >2 cm. RESULTS: Of the included 95 patients, 55 patients were node positive, with a total of 300 positive nodes. At a median follow-up of 25 months (interquartile range 9-46), the 3-year regional control was 91%. The 3-year involved nodal control rate was 96%. Involved nodal control was significantly higher in type I histology, nodes <2 cm and by radiation dose (75% for <55 Gy, 98% for 55 Gy in 25 fractions and 89% for >55 Gy, P = 0.03). The 3-year para-aortic failure rate for node negative patients treated with pelvis-only CRT was significantly higher with positron emission tomography/computed tomography (PET/CT) versus computed tomography (CT)-based staging (0% versus 20%). CONCLUSION: This is the largest study examining regional control rates of involved lymph nodes with CRT for patients who were not candidates for upfront extrafascial hysterectomy. Nodal failure was low following CRT and dose ≥55 Gy in 25 fractions seems to be adequate for involved nodes.

Tumor Control Probability of Radiosurgery and Fractionated Stereotactic Radiosurgery for Brain Metastases.

PURPOSE: As part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy, tumor control probability (TCP) after stereotactic radiosurgery (SRS) and fractionated stereotactic radiosurgery (fSRS) for brain metastases was modeled based on pooled dosimetric and clinical data from published English-language literature. METHODS AND MATERIALS: PubMed-indexed studies published between January 1995 and September 2017 were used to evaluate dosimetric and clinical predictors of TCP after SRS or fSRS for brain metastases. Eligible studies had ≥10 patients and included detailed dose-fractionation data with corresponding ≥1-year local control (LC) data, typically evaluated as a >20% increase in diameter of the targeted lesion using the pre-SRS diameter as a reference. RESULTS: Of 2951 potentially eligible manuscripts, 56 included sufficient dose-volume data for analyses. Accepting that necrosis and pseudoprogression can complicate the assessment of LC, for tumors ≤20 mm, single-fraction doses of 18 and 24 Gy corresponded with >85% and 95% 1-year LC rates, respectively. For tumors 21 to 30 mm, an 18 Gy single-fraction dose was associated with 75% LC. For tumors 31 to 40 mm, a 15 Gy single-fraction dose yielded ∼69% LC. For 3- to 5-fraction fSRS using doses in the range of 27 to 35 Gy, 80% 1-year LC has been achieved for tumors of 21 to 40 mm in diameter. CONCLUSIONS: TCP for SRS and fSRS are presented. For small lesions ≤20 mm, single doses of ≈18 Gy appear generally associated with excellent rates of LC; for melanoma, higher doses seem warranted. For larger lesions >20 mm, local control rates appear to be ≈ 70% to 75% with usual doses of 15 to 18 Gy, and in this setting, fSRS regimens should be considered. Greater consistency in reporting of dosimetric and LC data is needed to facilitate future pooled analyses. As systemic and biologic therapies evolve, updated analyses will be needed to further assess the necessity, efficacy, and toxicity of SRS and fSRS.

Sedation by non-anesthesiologists: are opioids and benzodiazepines outdated?

At least 3 systematic reviews have assessed the safety of propofol versus traditional agents used for sedation in gastrointestinal endoscopic procedures. These reviews uncovered a marked variability in study design and found the quality of the included randomized controlled trials to be poor. To date there is no demonstrated difference in the endoscopic safety or efficacy of propofol sedation compared to sedation with benzodiazepine with or without an opioid. However, a trend towards reduced complications and higher levels of satisfaction and cost-effectiveness with propofol during colonoscopies, and higher levels of patient satisfaction and improved efficacy may also be expected by using propofol during upper gastrointestinal endoscopies.

Computer-assisted propofol administration.

The use of propofol for sedation in endoscopy may allow for better quality of sedation, quicker recovery and facilitate greater throughput in endoscopy units. The cost-effectiveness and utility of propofol sedation for endoscopic procedures is contingent on the personnel and resources required to carry out the procedure. Computer-based platforms are based on the patients response to stimulation and physiologic parameters. They offer an appealing means of delivering safe and effective doses of propofol. One such means is the bispectral index where continuous EEG recordings are used to assess the degree of sedation. Another is the closed-loop target-controlled system where a set of physical parameters, such as muscle relaxation and auditory-evoked potential, determine a level of medication appropriate to achieve sedation. Patient-controlled platforms may also be used. These electronic adjuncts may help endoscopists who wish to adopt propofol sedation to change current practices with greater confidence.

Prospective comparison of radial and linear endoscopic ultrasound for diagnosis of chronic pancreatitis.

BACKGROUND AND STUDY AIMS: Linear endoscopic ultrasonography (EUS) is currently favored by many endosonographers for the evaluation of pancreatic pathology. However, radial EUS was used in early studies validating EUS for chronic pancreatitis. Radial and linear EUS have never been compared for the diagnosis of chronic pancreatitis. The aim of this study was to compare radial and linear EUS for the diagnosis of chronic pancreatitis using the secretin-stimulated endoscopic pancreatic function test (ePFT) as the reference standard. PATIENTS AND METHODS: One hundred consecutive patients evaluated for pain of possible pancreatic origin underwent combined radial EUS, linear EUS, and secretin ePFT during a single endoscopic session. EUS images were acquired on videotape and blindly scored by three reviewers. The main outcome measure was diagnostic accuracy. RESULTS: The accuracy of radial EUS and linear EUS (cutpoint > or = 4 criteria) was 84 % and 74 %, respectively. The statistical test for noninferiority was significant ( P < 0.001) suggesting that the accuracy of radial EUS is as good as or superior to linear EUS. The ratio of accuracy (pi (radial)/pi (linear)) was 1.14 (95 % confidence interval [CI] 0.99 to 1.28). No statistically significant differences were found between radial and linear EUS in terms of sensitivity, specificity, or overall discriminative ability (area under receiver operating characteristic curve 0.84 vs. 0.76, P = 0.10). Interobserver variability was similar for radial (Fleiss' kappa = 0.61, 95 %CI 0.43 to 0.79) and linear EUS (kappa = 0.50, 95 %CI 0.28 to 0.72). CONCLUSIONS: The accuracy of radial EUS is as good as linear EUS for the diagnosis of chronic pancreatitis.

Randomised clinical trial: gastrointestinal events in arthritis patients treated with celecoxib, ibuprofen or naproxen in the PRECISION trial.

AIM: To evaluate GI safety of celecoxib compared with 2 nonselective (ns) NSAIDs, as a secondary objective of a large trial examining multiorgan safety. METHODS: This randomised, double-blind controlled trial analysed 24 081 patients. Osteoarthritis or rheumatoid arthritis patients, needing ongoing NSAID treatment, were randomised to receive celecoxib 100-200 mg b.d., ibuprofen 600-800 mg t.d.s. or naproxen 375-500 mg b.d. plus esomeprazole, and low-dose aspirin or corticosteroids if already prescribed. Clinically significant GI events (CSGIE-bleeding, obstruction, perforation events from stomach downwards or symptomatic ulcers) and iron deficiency anaemia (IDA) were adjudicated blindly. RESULTS: Mean treatment and follow-up durations were 20.3 and 34.1 months. While on treatment or 30 days after, CSGIE occurred in 0.34%, 0.74% and 0.66% taking celecoxib, ibuprofen and naproxen. Hazard ratios (HR) were 0.43 (95% CI 0.27-0.68, P = 0.0003) celecoxib vs ibuprofen and 0.51 (0.32-0.81, P = 0.004) vs naproxen. There was also less IDA on celecoxib: HR 0.43 (0.27-0.68, P = 0.0003) vs ibuprofen; 0.40 (0.25-0.62, P < 0.0001) vs naproxen. Even taken with low-dose aspirin, fewer CSGIE occurred on celecoxib than ibuprofen (HR 0.52 [0.29-0.94], P = 0.03), and less IDA vs naproxen (0.42 [0.23-0.77, P = 0.005]). Corticosteroid use increased total GI events and CSGIE. H. pylori serological status had no influence. CONCLUSIONS: Arthritis patients taking NSAIDs plus esomeprazole have infrequent clinically significant gastrointestinal events. Co-prescribed with esomeprazole, celecoxib has better overall GI safety than ibuprofen or naproxen at these doses, despite treatment with low-dose aspirin or corticosteroids.

Argon plasma coagulation in chronic radiation proctitis.

Chronic radiation proctitis is a relatively common late complication of pelvic irradiation. The main symptoms are diarrhea, urgency, tenesmus, and rectal bleeding. While mild cases may settle spontaneously over some months, severe hemorrhagic radiation proctitis may require repeated blood transfusions and is difficult to treat with medical therapy. Argon plasma coagulation (APC) is a noncontact thermal coagulation technique which can be applied endoscopically. A probe passed through the scope delivers a field of argon gas to the mucosal surface where it is ionized by a high voltage filament, resulting in superficial mucosal heating and coagulation of friable blood vessels. The technique reduces rectal bleeding in 80%-90% of cases, and may improve the other troublesome symptoms of diarrhea and urgency. APC is probably less effective in very severe cases of hemorrhagic radiation proctitis; in these cases topical formalin or a combination of APC and topical formalin can be useful. Overall, APC has proved to be a safe and well tolerated technique.

Risk factors for cardiopulmonary events during propofol-mediated upper endoscopy and colonoscopy.

BACKGROUND: Propofol-mediated sedation for endoscopy is popular because of its rapid onset and recovery profile. AIM: To examine procedure-specific occurrence and risk factors for cardiopulmonary events during propofol-mediated upper endoscopy (EGD) and colonoscopy. DESIGN: A cohort study using the Clinical Outcomes Research Initiative database was used to determine the frequency of cardiopulmonary events. Clinical Outcomes Research Initiative consisted of 69 practice sites comprising 593 US endoscopists. Multivariate logistic regression analysis used variables, such as age, ASA classification and propofol administration by monitored anaesthesia care or gastroenterologist-administered propofol to determine the risk of cardiopulmonary events. RESULTS: The overall cardiopulmonary event rate for 5928 EGDs and 11 683 colonoscopies was 11.7/1000 cases. For colonoscopy, ascending ASA classification was associated with an increased risk. Monitored anaesthesia care was associated with a decreased adjusted relative risk (0.5, 95% CI: 0.36-0.72). ASA I and II patients receiving monitored anaesthesia care for EGD exhibited a significantly lower relative risk (ARR 0.29, 95% CI: 0.14-0.64). For subjects with ASA class III or greater, there was no difference in the risk between monitored anaesthesia care and gastroenterologist-administered propofol. CONCLUSIONS: There are procedure-specific risk factors for cardiopulmonary events during propofol-mediated EGD and colonoscopy. These should be taken into account during future prospective comparative trials.

Stage II Testicular Seminoma: Patterns of Care and Survival by Treatment Strategy.

AIMS: Stage II testicular seminoma is highly curable with radiotherapy or multi-agent chemotherapy (MACT). These modalities have not been compared in a randomised manner. MATERIALS AND METHODS: Using the US National Cancer Data Base, we identified 2437 stage II seminoma patients (IIA = 960, IIB = 812, IIC = 665) treated with orchiectomy and either radiotherapy or MACT from 1998 to 2012. Factors affecting treatment modality (radiotherapy versus MACT) were studied using multivariable logistic regression. Propensity scores for treatment selection were incorporated into multivariable Cox regression analyses of overall survival. RESULTS: The median follow-up was 65 months (interquartile range 34-106). Rates of radiotherapy utilisation were: IIA = 78.1%, IIB = 54.4%, IIC = 4.2%. Rates of MACT utilisation were: IIA = 21.9%, IIB = 45.6%, IIC = 95.8%. For both IIA and IIB patients, later year of diagnosis, academic treatment facility and pathological confirmation of lymph node positivity were associated with increased utilisation of MACT. Also predictive for preferential utilisation of MACT were comorbidity score ≥ 1 and non-private insurance for IIA patients and T stage ≥ 2 for IIB patients. For IIA patients, survival was improved with radiotherapy compared with MACT with a 5 year survival of 99.0% (95% confidence interval 98.2-99.8) versus 93.0% (95% confidence interval 89.0-97.0). This advantage persisted on propensity-adjusted multivariate analysis (hazard ratio 0.28; 95% confidence interval 0.09-0.86; P = 0.027). For IIB patients, 5 year survival was 95.2% (95% confidence interval 92.8-97.6) for radiotherapy and 92.4% (95% confidence interval 89.2-95.6) for MACT (Log-rank P = 0.041), with no significant difference on multivariable analysis. CONCLUSIONS: Radiotherapy is associated with improved survival over MACT for IIA patients, with no significant survival difference for IIB patients.

Does paclitaxel improve the chemoradiotherapy of locoregionally advanced esophageal cancer? A nonrandomized comparison with fluorouracil-based therapy.

PURPOSE: A phase II trial of accelerated fractionation radiation with concurrent cisplatin and paclitaxel chemotherapy was performed to investigate the role of the paclitaxel, when substituted for fluorouracil (5-FU), in the chemoradiotherapy of esophageal cancer. PATIENTS AND METHODS: Patients with an esophageal ultrasound stage of T(3) or N(1) or M(1) (nodal) esophageal cancer were treated with two courses of a cisplatin infusion (20 mg/m(2)/d for 4 days) and paclitaxel (175 mg/m(2) over 24 hours) concurrent with a split course of accelerated fractionation radiation (1.5 Gy bid to a total dose of 45 Gy). Surgical resection was performed 4 to 6 weeks later followed by a single identical postoperative course of chemoradiotherapy (24 Gy) in patients with significant residual tumor at surgery. Toxicity and results of this treatment were retrospectively compared with our previous 5-FU and cisplatin chemoradiotherapy experience. RESULTS: Between September 1995 and July 1997, 40 patients were entered onto this study. Although dysphagia proved worse in our 5-FU-treated patients, profound leukopenia and a need for unplanned hospitalization were significantly more common in the paclitaxel group. Thirty-seven patients (93%) proved resectable for cure. The 3-year projected overall survival is 30%, locoregional control is 81%, and distant metastatic disease control is 44%. When compared with a similarly staged cohort of 5-FU-treated patients, there was no advantage for any survival function studied. CONCLUSION: This paclitaxel-based treatment regimen for locoregionally advanced esophageal cancer produced increased toxicity with no improvement in results when compared with our previous 5-FU experience. Paclitaxel-based treatments must be carefully and prospectively studied before their incorporation into the standard management of esophageal cancer.

Reduced eticlopride-induced Fos expression in caudate-putamen and globus pallidus after unilateral frontal cortex injury: relation to neglect.

Unilateral ablation of medial agranular cortex in rats results in neglect of contralateral stimuli and reductions in amphetamine-induced expression of the immediate early gene, c-fos, in both caudate-putamen and globus pallidus. Both unilateral neglect and the reductions in dopamine agonist induction of subcortical Fos immunoreactivity dissipate over a matter of weeks. Dopamine agonism induces Fos predominantly in striatonigral cells and in globus pallidus via striatopallidal disinhibition, whereas Fos is induced in striatopallidal cells by administration of antagonists of the D2 dopamine receptor subfamily. To examine more directly effects of cortical injury on striatopallidal function, induction of striatal Fos by the D2 antagonist eticlopride (0.1 mg/kg, s.c.) was examined in rats with medial agranular cortex ablation. In the same animals, eticlopride-induced Fos in globus pallidus was also examined. Five days after unilateral cortex injury, in rats showing neglect, the numbers of Fos immunoreactive nuclei induced by eticlopride were reduced by 50% in caudate-putamen and 25% in globus pallidus of the ipsilateral hemisphere. These lesion effects were restricted to dorsolateral caudate-putamen and dorsal pallidum. Three or more weeks after cortical injury, in rats recovered from neglect, eticlopride-induced Fos was normalized in caudate-putamen, but still decreased by 20% in globus pallidus. Along with previous findings, these results suggest that behavioral recovery from neglect produced by cortical injury may be at least partially mediated by normalizations of function of both striatopallidal and striatonigral neurons. In addition, the present findings suggest that normalization of function of pallidal cells activated by eticlopride is not necessary for behavioral recovery from frontal cortex ablation. Lingering reductions in excitatory cortico-subthalamo-pallidal input may be responsible for the longer-lasting dysfunctions of these pallidal cells.

Gastric antral vascular ectasia: a case report and review of the literature.

UNLABELLED: We present an 83-yr-old woman with a history of renal insufficiency, diabetes and idiopathic purpura (ITP) who experienced recurrent hemorrhage from gastric antral vascular ectasias (GAVE). METHODS: Extensive evaluation consisting of barium small bowel series, colonoscopy, abdominal CT scan and visceral angiography excluded other causes of bleeding. RESULTS: After 99mTc-labeled red cell imaging to localize the bleeding to the antrum, an antrectomy was performed. Seven months postsurgery, the patient experienced no further hemorrhage. CONCLUSION: 99mTc-labeled red cell scans can be used for the diagnosis of GAVE.

Plasma DNA. A simple, rapid test for aiding the diagnosis of pulmonary embolism.

Previously, we reported that the sensitivity of plasma DNA for patients with pulmonary emboli was 83 to 88 percent. To confirm these findings in a more comprehensive study, we collected plasma samples from 137 consecutive patients undergoing 148 ventilation-perfusion lung scans for pulmonary embolism. DNA was measured using a counter-immunoelectrophoresis technique that used high titer precipitating double-stranded DNA antibody from a patient with systemic lupus erythematosus. In addition to 17 patients (17 lung scans) excluded for not having plasma collected, 32 patients (37 lung scans) were excluded for having either a condition other than pulmonary embolism that could be associated with plasma DNA or for having nonacute symptoms. Eighteen of 22 patients with a diagnosis of pulmonary embolism (defined by either a high probability lung scan or abnormal pulmonary angiogram) had detectable plasma DNA. Only four of 27 patients without pulmonary embolism (defined by either a normal lung scan or normal pulmonary angiogram) had plasma DNA detected. Based on these results, plasma DNA had a sensitivity of 82 percent and a specificity of 85 percent for this condition. Plasma DNA is a promising test for pulmonary embolism and could help physicians interpret equivocal lung scan findings and thereby clarify difficult decisions such as the need for pulmonary angiography.

N1 esophageal carcinoma: the importance of staging and downstaging.

OBJECTIVE: To evaluate the effects of clinical staging and downstaging by induction chemoradiation therapy in patients with N1 esophageal carcinoma. METHODS: Sixty-nine consecutive patients with regional lymph node metastases (cN1) according to clinical staging received induction therapy before surgery. These were compared to 75 patients both clinically and pathologically N1 (cN1/pN1) who underwent surgery without induction therapy and 79 patients clinically and pathologically not N1 (cN0/pN0) who underwent surgery without induction therapy. Analyses focused on survival and the cost and benefit of therapy. RESULTS: For comparison, the extremes of 5-year survival were 69% for cN0/pN0 patients who underwent surgery alone and 12% for cN1/pN1 patients who underwent surgery alone. Of 69 patients who received induction therapy, 37 were pN0 at resection (downstaged); they had an intermediate survival of 37% at 5 years. Those patients not downstaged with induction therapy had a 12% 5-year survival, similar to patients with cN1/pN1 who underwent surgery alone. After adjusting for the strongest predictors of poor outcome, pN1, and increasing N1 burden, a modest increased risk of death after induction therapy was identified. However, this cost of induction therapy was more than counterbalanced by the benefit of improved survival of downstaging to pN0. CONCLUSIONS: (1) pN1 is the strongest determinant of poor outcome. (2) cN1 patients who are downstaged by induction chemoradiation therapy to pN0 have an intermediate outcome. (3) cN1 patients who are not downstaged by induction therapy have a poor outcome.