Gene expression patterns and profile changes pre- and post-erlotinib treatment in patients with metastatic breast cancer.

PURPOSE: To delineate gene expression patterns and profile changes in metastatic tumor biopsies at baseline and 1 month after treatment with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib in patients with metastatic breast cancer. EXPERIMENTAL DESIGN: Patients were treated with 150 mg of oral erlotinib daily. Gene expression profiles were measured with Affymetrix U133A GeneChip and immunohistochemistry was used to validate microarray findings. RESULTS: Estrogen receptor (ER) status by immunohistochemistry is nearly coincided with the two major expression clusters determined by expression of genes using unsupervised hierarchical clustering analysis. One of 10 patients had an EGFR-positive tumor detected by both microarray and immunohistochemistry. In this tumor, tissue inhibitor of metalloproteinases-3 and collagen type 1 alpha 2, which are the EGF-down-regulated growth repressors, were significantly increased by erlotinib. Gene changes in EGFR-negative tumors are those of G-protein-linked and cell surface receptor-linked signaling. Gene ontology comparison analysis pretreatment and posttreatment in EGFR-negative tumors revealed biological process categories that have more genes differentially expressed than expected by chance. Among 495 gene ontology categories, the significant differed gene ontology groups include G-protein-coupled receptor protein signaling (34 genes, P = 0.002) and cell surface receptor-linked signal transduction (74 genes, P = 0.007). CONCLUSIONS: ER status reflects the major difference in gene expression pattern in metastatic breast cancer. Erlotinib had effects on genes of EGFR signaling pathway in the EGFR-positive tumor and on gene ontology biological process categories or genes that have function in signal transduction in EGFR-negative tumors.     

Flerobuterol: a potential antidepressant drug related to β-adrenergic agonists. Experimental profile in mice

The potential antidepressant effect of flerobuterol (dl-(fluoro-2 phenyl)-1 t-butylamino-2 ethanol), a new drug related to beta-adrenoceptor agonists, was evaluated and compared with imipramine and salbutamol using classical psychopharmacological tests in mice. Like imipramine and salbutamol, flerobuterol (0.5-32 mg kg-1, ip) fully prevented apomorphine (16 mg kg-1, sc)- and partly reversed reserpine- and oxotremorine-induced hypothermia. At higher doses (16-32 mg kg-1), flerobuterol enhanced the toxic effects of yohimbine. Unlike imipramine, flerobuterol and salbutamol did not reduce immobility duration in the behavioural despair test. Salbutamol and flerobuterol decreased locomotor activity. Flerobuterol did not induce mydriasis, did not prevent oxotremorine-induced tremors or salivary and lacrimal gland secretion and did not reduce reserpine-induced palpebral ptosis. Propranolol (8 mg kg-1, ip) but not alpha-methyl-paratyrosine (75 mg kg-1, ip) prevented the flerobuterol-induced antagonism of apomorphine-induced hypothermia. Our results suggest that flerobuterol demonstrates potential antidepressant activity, which could be related to beta-adrenoceptor activation in mice.     

Retrospective review of pemetrexed with or without platinum in malignant mesothelioma: The Australian 'Special Access Scheme' experience

Background: Pemetrexed and cisplatin have recently been shown to significantly improve survival compared with cisplatin alone. However, there are only limited data reflecting teaching hospital experience outside a clinical trial. Pemetrexed has only been available in Australia on a restricted basis since 2002. We reviewed our experience of patients treated on the Australian ‘Special Access Scheme’ at three major thoracic oncology units. Methods: Charts were reviewed for all patients enrolled on the scheme. Data was extracted on age, World Health Organization (WHO) performance status, histology, prior therapy, time from diagnosis to starting pemetrexed, chemotherapy (pemetrexed alone or with a platinum), cycle number, response rate, actuarial progression‐free and overall survival. Doses were cisplatin 75 mg/m² or carboplatin AUC = 5 and pemetrexed 500 mg/m² every 21 days. Results: 52 patients (32 male and 20 female) were reviewed. Median age was 58 years and 88% were WHO 0–1. Histology included 54% epithelial, 17% biphasic (epithelial and sarcomatoid) and 21% undefined. The median time from diagnosis to administration of pemetrexed was 145 days. Sixty‐five percent had minimal surgical intervention with video assisted thoracoscopy, pleurodesis and biopsy, while 19% had received prior palliative radiation. Seventy‐one percent were chemotherapy naïve, the remaining 29% having received previous platinum and/or gemcitabine regimens. Twenty‐three percent had pemetrexed alone, 35% in combination with carboplatin and 42% with cisplatin. The median number of cycles was 4 (range 1–13). The response rate was 33%. No toxicity was observed in 20% grade 3–4 toxicity in 10% (majority nausea/vomiting). The median progression‐free and overall survival times from starting pemetrexed were 184 days and 298 days, respectively. Conclusions: Pemetrexed‐based regimens are safe and effective in a community setting in malignant mesothelioma.     

Comparison of Laparoscopic vs Open Sigmoid Colectomy for Benign and Malignant Disease at Academic Medical Centers

Few studies have examined outcomes of laparoscopic and open sigmoid colectomy performed at US academic centers. Using ICD-9 diagnosis and procedural codes, data was obtained from the University HealthSystem Consortium (UHC) Clinical Database of 10,603 patients who underwent laparoscopic or open sigmoid colectomy for benign and malignant disease between 2003–2006. A total of 1,092 patients (10.3%) underwent laparoscopic sigmoid colectomy. Laparoscopic sigmoid colectomy was associated with a significantly shorter length of stay (5.4 vs 7.4 days), lower overall complication rate (19.7 vs 26.0%), lower 30-day readmission rate (3.4 vs 4.6), and a lower hospital cost ($13,814 vs $15,626). When a subset analysis of malignant and benign groups was performed, a significantly shorter length of stay in both the malignant laparoscopic group (6.4 ± 6.4 vs 7.8 ± 6.6 days) and in the benign laparoscopic groups (5.1 ± 3.5 vs 7.2 ± 7.6) exists. A lower wound complication rate (2.1 vs 5.5%, malignant and 4.0 vs 6.1, benign) is also evident. Laparoscopic sigmoid colectomy was associated with a shorter length of stay, less complications, and a lower 30-day readmission rate. The shorter length of stay and wound infection rate maintain significance when comparing laparoscopic vs open sigmoid resections for malignant and benign disease. Presented at the 48th annual meeting of the Society for Surgery of the Alimentary Tract at Digestive Disease Weak, Washington, DC, May 21st 2007. The information contained in this article was based on the Clinical Data Base provided by the University HealthSystem Consortium.     

Internal Hernias: Clinical Findings,Management, and Outcomes in 49 Nonbariatric Cases

Internal hernia, the protrusion of a viscus through a peritoneal or mesenteric aperture, is a rare cause of small bowel obstruction. We report the clinical presentation, surgical management, and outcomes of one of the largest series of nonbariatric internal hernias. Ten-year retrospective review of patients at our institution yielded 49 cases of internal hernias. Majority of patients presented with symptoms of acute (75%) or intermittent (22%) small bowel obstruction. While 16% of CT scans were suspicious for internal hernia, in no cases the preoperative diagnosis of internal hernia was made. The most frequent internal hernias were transmesenteric (57.0%) and 34 hernias (69%) were caused by previous surgery. All internal hernias were reduced and the defects were repaired. Compromised bowel was present in 22 cases and 11 patients underwent small bowel resection. The mean postoperative hospitalization was 10.9 days. The overall mortality rate from our series is 2%, and the morbidity rate is 12%. Transmesenteric hernias, as complications of previous surgeries, are the most prevalent internal hernias. Preoperative diagnosis of internal hernia is extremely difficult because of the nonspecific clinical presentation. However, if discovered promptly, internal hernias can be repaired with acceptable morbidity and mortality. Poster presentation at Digestive Disease Week, May 22, 2006, Los Angeles, California, USA.     

Socio-economic burden of permanent incisor replantation on children and parents

Abstract – This study describes the socio‐economic burden and attitudes of children and their parents following replantation of avulsed incisors. Records of 80 patients with 99 avulsion injuries treated in a teaching hospital clinic from 1988 to 1999 were reviewed. Mean age at time of injury was 10.6 years (range = 6.6–17.7 years). Complete records for a minimum of 1 year were obtained for 43 patients with 60 replanted incisors. Mean treatment procedures provided during the first year included 5.5 diagnostic periapical radiographs, 1.9 occlusal radiographs, 1.3 pulpectomies, and 2.7 pulp medicament applications. The mean estimated treatment cost and direct time (dentist) for first‐year post‐trauma management was $1465 CAD and 7.2 h, respectively. Treatment costs were significantly higher during the first year post‐trauma for patients who had their incisors extracted (P = 0.04), but there was no significant difference in direct treatment time between the two groups (P = 0.19). Twenty‐one patient–parent pairs were surveyed for a number of qualitative factors. Ninety per cent of patients and 86% of parents reported that school and work time was lost. Even after having gone through the painful experience of replantation, the demands of recall, and in some cases, extraction, the majority of patients (67%) and parents (81%) stated that they would have still made the same (replantation) decision. Patient and parent responses were not statistically different (P = 0.453). Almost half the parents stated they would be willing to pay over $2000 CAD to save an incisor. Patients rated retention of an incisor as significantly more important than infraocclusion. This is the first study to quantify the treatment burden of replantation of avulsion injuries exclusively in the pediatric population. This study describes the socio‐economic burden and responsibilities of patient/parent and dentist and their role in informed consent.