Gefitinib in definitive management of esophageal or gastroesophageal junction cancer: a retrospective analysis of two clinical trials.

The role of epidermal growth factor receptor inhibition in resectable esophageal/gastroesophageal junction (E/GEJ) cancer is uncertain. Results from two Cleveland Clinic trials of concurrent chemoradiotherapy (CCRT) and surgery are updated and retrospectively compared, the second study differing only by the addition of gefitinib (G) to the treatment regimen. Eligibility required a diagnosis of E/GEJ squamous cell or adenocarcinoma, with an endoscopic ultrasound stage of at least T3, N1, or M1a (American Joint Committee on Cancer 6th). Patients in both trials received 5-fluorouracil (1000 mg/m(2) /day) and cisplatin (20 mg/m(2) /day) as continuous infusions over days 1-4 along with 30 Gy radiation at 1.5 Gy bid. Surgery followed in 4-6 weeks; identical CCRT was given 6-10 weeks later. The second trial added G, 250 mg/day, on day 1 for 4 weeks, and again with postoperative CCRT for 2 years. Preliminary results and comparisons have been previously published. Clinical characteristics were similar between the 80 patients on the G trial (2003-2006) and the 93 patients on the no-G trial (1999-2003). Minimum follow-up for all patients was 5 years. Multivariable analyses comparing the G versus no-G patients and adjusting for statistically significant covariates demonstrated improved overall survival (hazard ratio [HR] 0.64, 95% confidence interval [CI] = 0.45-0.91, P = 0.012), recurrence-free survival (HR 0.61, 95% CI = 0.43-0.86, P = 0.006), and distant recurrence (HR 0.68, 95% CI = 0.45-1.00, P = 0.05), but not locoregional recurrence. Although this retrospective comparison can only be considered exploratory, it suggests that G may improve clinical outcomes when combined with CCRT and surgery in the definitive treatment of E/GEJ cancer.

Randomized phase II trial of pemetrexed/cisplatin with or without CBP501 in patients with advanced malignant pleural mesothelioma.

BACKGROUND: CBP501, a synthetic duodecapeptide, increases cisplatin influx into tumor cells through an interaction with calmodulin enhancing cisplatin cytotoxicity, and effects cell cycle progression by abrogating DNA repair at the G2 checkpoint. In phase I clinical trials of CBP501 alone or in combination with cisplatin, the most common toxicity was infusion-related urticaria. Activity of CBP501 plus cisplatin was observed in patients with ovarian cancer and mesothelioma, including some patients previously treated with cisplatin. METHODS: Chemotherapy naïve patients with unresectable MPM were stratified by histology and performance status, and randomized 2:1 to pemetrexed/cisplatin plus CBP501 25mg/m(2) IV (Arm A) or pemetrexed/cisplatin alone (Arm B). The primary endpoint was progression free survival (PFS) at 4 months. RESULTS: 65 patients were randomized, and 63 were treated. Patient characteristics in the two arms were balanced. Based on independent radiology review of the treated population, 25/40 patients (63%) in Arm A and 9/23 (39%) in Arm B had PFS≥4mo; the median PFS was 5.1mo (95% CI, 3.9, 6.5) vs 3.4mo (2.5, 6.7). Median OS was 13.3mo (9.2, 16.3) in Arm A and 12.8 (6.5, 16.1) in Arm B. Adverse events were not different than expected from standard chemotherapy, and comparable in the two arms, aside from infusion reactions which occurred in 70% of patients treated with CBP501. CONCLUSIONS: While this randomized phase II trial met its primary endpoint of PFS at 4 months, other parameters such as response rate and overall survival suggest that the addition of CBP501 does not improve the efficacy of standard chemotherapy for MPM.

Clinicopathologic features and treatment outcomes of patients with human epidermal growth factor receptor 2-positive adenocarcinoma of the esophagus and gastroesophageal junction.

Human epidermal growth factor receptor 2 (HER2) is overexpressed in 21% of gastric and 33% of gastroesophageal junction (GEJ) adenocarcinomas. Trastuzumab has been approved for metastatic HER2-positive gastric/GEJ cancer in combination with chemotherapy. This retrospective analysis was undertaken to better define the clinicopathologic features, treatment outcomes, and prognosis in patients with HER2-positive adenocarcinoma of the esophagus/GEJ. Pathologic specimens from 156 patients with adenocarcinoma of the esophagus/GEJ treated on clinical trials with chemoradiation and surgery were tested for HER2. Seventy-six patients also received 2 years of gefitinib. Baseline characteristics and treatment outcomes of the HER2-positive and negative patients were compared both in aggregate and separately for each of the two trials. Of 156 patients, 135 had sufficient pathologic material available for HER2 assessment. HER2 positivity was found in 23%; 28% with GEJ primaries and 15% with esophageal primaries (P= 0.10). There was no statistical difference in clinicopathologic features between HER2-positive and negative patients except HER2-negative tumors were more likely to be poorly differentiated (P < 0.001). Locoregional recurrence, distant metastatic recurrence, any recurrence, and overall survival were also statistically similar between the HER2-positive and the HER2-negative groups, in both the entire cohort and in the gefitinib-treated subset. Except for tumor differentiation, HER2-positive and negative patients with adenocarcinoma of the esophagus and GEJ do not differ in clinicopathologic characteristics and treatment outcomes. Given the demonstrated benefit of trastuzumab in HER2-positive gastric cancer and the similar incidence of HER2 overexpression in esophageal/GEJ adenocarcinoma, further evaluation of HER2-directed therapy in this disease seems indicated.

Activity of the equine rectus abdominis and oblique external abdominal muscles measured by surface EMG during walk and trot on the treadmill.

REASON FOR PERFORMING STUDY: The rectus abdominis (RA) and oblique external abdominal (OEA) muscles are both part of the construction of the equine trunk and thought to be essential for the function of the spine during locomotion. Although RA activity at trot has previously been investigated, the relationship between OEA and RA at walk and trot has not yet been described. OBJECTIVES: To document abdominal muscle activities during walk and trot, and test the hypothesis that muscle activity at walk would be smaller than at trot. MATERIALS AND METHODS: Six horses (8-20 years old, 450-700 kg) were used for surface electromyography (EMG) measurements, with EMG electrodes placed caudal to the sternum (RA) and at the level of the 16th rib (OEA). On all hooves, the withers and the sacrum reflective markers were placed to determine motion cycles. Normal distribution of data was tested using a Kolmogorov-Smirnov test and Student's t test was used to compare left-right and walk-trot differences (P < 0.05). RESULTS: Minimum, maximum and mean EMG values recorded at walk were significantly higher at trot than at walk in all horses for OEA and in 5/6 horses for RA. At walk, EMG activity ranged from 8-44 mV (RA) and 7-54 mV (OEA). At trot, EMG activity ranged from 18-150 mV (RA) and 27-239 mV (OEA). There were statistically significant differences between maximum activities of left and right OEA and RA muscles at walk in all horses, and in 4/6 horses at trot. CONCLUSIONS: Muscle activities of OEA and RA are smaller at walk than at trot. At walk, the OEA/RA ratio is lower than at trot. There are more significant correlations between muscle activities of both RA and OEA and limb movements at walk than at the trot.

A cross-sectional examination of growth indicators from Nicaraguan adolescent girls: a comparison of anthropometric data from their Guatemalan counterparts.

BACKGROUND: Few studies have examined growth data from adolescent girls in Latin America and almost none have been conducted in Nicaragua. Thus this study examines growth data from Nicaraguan adolescent girls. AIM: This study describes cross-sectional growth data from a sample of Nicaraguan girls. These data are compared with data from Mexican-US and Guatemalan girls. It is hypothesized that (a) Mexican-US and Guatemalan wealthy ladina girls will show better indicators of nutritional status when compared with the Nicaraguan girls, and (b) the Nicaraguan girls will show similar anthropometric indicators when compared with poor Guatemalan girls. SUBJECTS AND METHODS: Anthropometric and age at menarche data were collected from a sample of 154 adolescent girls ages 10-17 years living in Managua, Nicaragua. RESULTS: The findings revealed that these girls are significantly shorter and lighter than US, Mexican-US and wealthy Guatemalan adolescent girls. These girls are also significantly taller and heavier than their poor Guatemalan counterparts. CONCLUSION: This study reveals that the Nicaraguan girls are undernourished when compared with other Latin American girls living in an improved overall environment. The data also reveal that the Nicaraguan girls have better indicators of nutritional status when compared with a cohort of poor Guatemalan girls.

Cardiovascular reactivity and initiate/avoid patterns of marital communication: a test of Gottman's psychophysiologic model of marital interaction.

Gottman's (1990, 1991; Gottman and Levenson, 1988) psychophysiologic model of marital interaction was tested in 60 married couples. Participants were classified as avoiders or initiators of relationship problem discussions by trained coders observing videotaped semistructured interviews. Blood pressure (BP) and heart rate reactivity was assessed during the cold pressor test, during a mental math test, while watching a marital argument on video, and during a conjoint interview. As hypothesized, avoiders had significantly greater systolic BP reactivity during the interview. Additionally, husbands who interacted with avoider wives had significantly greater diastolic and systolic BP reactivity than did husbands of initiator wives. Initiator husbands, in particular, who were married to avoider wives had greater systolic BP reactivity. These results both support Gottman's psychophysiologic model and suggest modifications of it.

A randomized trial of emotion-focused therapy for couples in a training clinic.

Forty married couples participated in a randomized trial comparing 8 weekly sessions of emotion-focused therapy (EFT) for couples to a group of couples who were placed on an 8-week waiting list. A composite marital satisfaction score was created from scores on the Dyadic Adjustment Scale, Positive Feelings Questionnaire, and Personal Assessment of Intimacy in Relationships scale. Controlling for pretest scores, participants in the treatment group had significantly higher levels of marital satisfaction after 8 weeks than wait-list participants. Supplementary analyses identified variables associated with gains in therapy and with dropping out of the study.

[Tumors caused by methylcholanthrene and lapachol. Follow-up of development with cytology]. / Tumores provocados por metilcolantreno y lapachol. Seguimiento del desarrollo mediante citología.

This present work was carried out in order to study the effect of Lapachol (LAP) administrated to rats simultaneously with a chemical carcinogen 20-Methylcholanthrene (MCA). Animals were divided in 4 groups: A-Group treated with 80 mg of MCA I(n = 11 rats), B-Group treated with 80 mg of MCA+LAP 100 mg/kg weight/day, (n = 15 rats), C-Group treated with LAP 100 mg/kg weight/day (n = 12 rats), D-Group control-no treatment (n = 13 rats). Cytological studies as well as cytochemical techniques allowed the recognition of benign and malignant conditions at the time of the tumor appearance. Histopathological evaluation posteriorly confirmed the development of tumors in 53% of the animals in group B. Morphologically consistent with poorly differentiated adenocarcinomas of the salivary glands and fibroadenomas of the breast in 18.2% (2/11) of the rats in group A. Besides the presence of one or several supra-hepatic nodules in vecinity of the suspensory ligament corresponding to nodular hyperplasia were observed in 33% (4/12) of group C and in 13.3% (12/15) of group B. No nodules were observed in groups A and D. Tubular dilatation of kidneys were noted in 60% (9/15) and 83.3/ (10/12) of the rats in group E and C respectively. From the original salivary gland tumor a series of transplantables tumors were developed and followed by cytological evaluations. The importance of the cytological and histopathological diagnosis for the pharmacological effects studies of certain drugs like Lapachol that are widely used as antitumoral agents without exact knowledge of the adverse effects is emphasized.