The carina is not a landmark for central venous catheter placement in neonates

BACKGROUND: Cardiac tamponade is rare but one of the most serious complications in relation to central venous catheters (CVC). The tip of the CVC should be placed outside the pericardium to avoid tamponade. In adults, the carina is always located above the pericardium; therefore, the carina is a reliable landmark for CVC placement. We examined whether the carina could also be an adequate landmark for CVC placement in neonates. METHODS: The study was conducted using nine fresh neonatal cadavers. The longitudinal distance between the carina and the pericardium as it transverses the superior vena cava (the pericardial reflection: PR) was measured. RESULTS: The median postconceptional age (gestational age in weeks + weeks after delivery) at autopsy was 35 (range: 23-42) weeks. The PR was located at a distance of 4 mm above to 5 mm below the carina. Unlike in adults, the position of the PR varies in relation to the carina in neonates. In seven of the nine subjects, the location of the PR was above the carina. CONCLUSIONS: In neonates, the carina is not always located above the pericardium, as it is in adults; therefore, the carina is not an appropriate landmark for CVC placement.     

Absence of beta-catenin alteration in hepatic tumors induced by p-nitroanisole in Crj:BDF1 mice

In the present study, beta-catenin localization in hepatocellular neoplasms and hepatoblastomas, induced by oral administration of p-Nitroanisole (pNA) in Crj:BDF1 for 2 years, was evaluated by immunohistochemistry along with genetic alterations in exon 2 of beta-catenin by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) approach. Genomic DNA was isolated from paraffin sections of a total of 53 liver tumors. Immunohistochemical analysis revealed no abnormal accumulation of the beta-catenin protein in any of the cases. No mutations (0/13), 20% silent mutations (3/15) and 8% silent plus 12% functional mutations (2 + 3/25), not in the multiple phosphorylation sites of beta-catenin, were observed in hepatocellular adenomas, carcinomas and hepatoblastomas, respectively. The results indicate that beta-catenin does not play an important role in development of hepatic tumors induced by pNA in Crj:BDF1 mice.     

Existence of no hepatocarcinogenic effect levels of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline with or without coadministration with ethanol

There is increasing evidence of the existence of no effect levels for genotoxic carcinogens. However, only limited information is available regarding dose-response curves for combination effects of multiple carcinogens at low dose. In the present study, 280 male F344 rats were divided into 14 groups to determine the effects of co-administration of various doses of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 10% ethanol on the development of glutathione S-transferase placental form (GST-P)-positive foci in the liver. The results provided concrete evidence for the existence of no effect levels for hepatocarcinogenicity of MeIQx either in presence or absence of ethanol and, therefore, for a practical threshold for this genotoxic carcinogen.     

Prospective study of gefitinib readministration after chemotherapy in patients with advanced non-small-cell lung cancer who previously responded to gefitinib

IntroductionSalvage treatment for acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitor in patients with non–small-cell lung cancer is a matter of clinical concern. Several retrospective reports have indicated the usefulness of epidermal growth factor receptor tyrosine kinase inhibitor readministration; however, there have been few prospective studies.Materials and MethodsThis study was designed to prospectively evaluate the clinical efficacy of gefitinib readministration in patients with advanced or metastatic non–small-cell lung cancer who responded well to initial gefitinib treatment. The subjects received at least 1 regimen of cytotoxic chemotherapy after progressive disease with the initial gefitinib therapy. Gefitinib administration (250 mg/d, orally) was started after progressive disease with the previous chemotherapeutic regimen. The primary endpoint in the present study was the response rate.ResultsTwenty patients were enrolled between April 2007 and May 2011. Three patients achieved partial response, and 6 showed stable disease. Thus, the overall response rate and disease control rate of gefitinib readministration were 15% (95% CI, 3.21-37.9) and 45% (95% CI, 23.1-68.5), respectively. Median progression-free survival and overall survival from the start of gefitinib readministration were 2.0 months (95% CI, 0.9-3.1 months) and 12.0 months (95% CI, 8.0-16.0 months), respectively.ConclusionThese results suggest that gefitinib readministration may be an option, albeit with a low response rate and short progression-free survival, for patients who responded well to initial gefitinib followed by systemic chemotherapy. These findings provide valuable information for the management of previous gefitinib responders.     

Evaluation of Intrahepatic Perfusion on Fusion Imaging Using a Combined CT/SPECT System: Influence of Anatomic Variations on Hemodynamic Modification Before Installation of Implantable Port Systems for Hepatic Arterial Infusion Chemotherapy

BACKGROUND: In some patients with hepatic tumors, anatomic variations in the hepatic arteries may require hemodynamic modification to render effective hepatic arterial infusion chemotherapy delivered via implantable port systems. We used a combined CT/SPECT system to obtain fused images of the intrahepatic perfusion patterns in patients with such anatomic variations and assessed their effects on the treatment response of hepatic tumors. METHODS: Using a combined SPECT/CT system, we obtained fused images in 110 patients with malignant liver tumors (n = 75) or liver metastasis from unresectable pancreatic cancer (n = 35). Patients with anatomic hepatic arteries variations underwent hemodynamic modification before the placement of implantable port systems for hepatic arterial infusion chemotherapy. We evaluated their intrahepatic perfusion patterns and the initial treatment response of their liver tumors. The perfusion patterns on the fused images were classified as homogeneous, local hypoperfusion, and/or perfusion defect. Using the WHO criteria of complete response (CR), partial response (PR), no change (NC), and progressive disease (PD), we evaluated the patients' tumor responses after 3 months on multislice helical CT scans. The treatment was regarded as effective in patients who achieved a complete response or partial response. RESULTS: Anatomic hepatic artery variations were present in 15 of the 110 patients (13.6%); 5 manifested replacement of the left hepatic artery (LHA), 8 of the right hepatic artery (RHA), and 1 each had replacement of the RHA and LHA, and replacement of the LHA plus an accessory RHA. In 13 of these 15 patients (87%), occlusion with metallic coils was successful. On fusion imaging, the perfusion patterns were recorded as homogeneous in 6 patients (43%), as hypoperfusion in 7 (50%), and 1 patient had a perfusion defect (7.1%) in the embolized arterial region. Of the 8 patients with RHA replacement, 4 manifested a homogeneous distribution and 3 hypoperfusion. In 2 of 5 patients with LHA replacement, the distribution was homogeneous. In 1 patient with RHA and LHA replacement, and in 1 patient with LHA replacement and an accessory RHA, we noted hypoperfusion in the RHA territory. All 6 patients with homogeneous distribution were classified as PR or NC on follow-up multidetector CT. Of the 7 patients manifesting hypoperfusion, 3 were classified as PD (43%), 3 as NC (43%), and 1 as PR (14%) on follow-up CT. CONCLUSION: Hemodynamic modification of anatomic hepatic artery variations resulted in hypoperfusion on fusion images. Differences in the intrahepatic perfusion patterns may affect the response to hepatic arterial infusion chemotherapy.     

Quantification of circulating plasma DNA fragments as tumor markers in patients with esophageal and gastric cancer

The quantity and quality of circulating DNA fragments was analyzed by quantitative real-time polymerase chain reactions (qPCR) in plasma from patients with esophageal and gastric cancer, in order to assess their diagnostic value. Plasma was collected preoperatively from 24 patients with esophageal cancer 53 patients with gastric cancer and from 21 healthy controls. qPCR was performed using two primer sets for the BETA-actin gene, amplifying short (102 bp) and long (253 bp) segments. The DNA concentrations in both the short and long segment assays of both cancer patients were significantly higher than the controls. The difference of concentrations between disease group and controls was more significant in esophageal cancer patients. The area under the receiver-operating characteristic curve was 0.83 (short) and 0.91 (long) for esophageal cancer patients, and 0.75 (short) and 0.67 (long) for gastric cancer versus the controls. There was also a significant difference in DNA integrity (short/long) between esophageal cancer patients and the control group (p = 0.001). qPCR assays for plasma DNA concentrations and their integrity can serve as new diagnostic markers for screening and monitoring patients with esophageal and gastric cancer.     

Promotion of chemically induced rat esophageal tumorigenesis with post-initiation ethanol modification.

Post-initiation ethanol modification on N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal carcinogenesis model was investigated in male, 6-week-old, F344 rats that received s.c. injections, 3 times per week, of 0.5 mg/kg NMBA for the first 5 weeks and then were treated with 0% (Group 1), 3.3% (Group 2), and 10% (Group 3) ethanol in the drinking water for up to 20 weeks. Group 4 received 10% ethanol without NMBA administration and Group 5 was maintained without any chemical treatment. There were no statistical differences in the incidence and multiplicity of esophageal tumors among Groups 1 to 3. However, the multiplicity of hyperplasias was statistically greater in Group 3 than in Groups 1 or 2. Esophageal epithelia of all rats in Groups 4 and 5 demonstrated a normal histology. BrdU labelling indices of tumors and hyperplasias in NMBA-treated groups were essentially similar, although cycline D1 was overexpressed to a greater extent in tumors and also hyperplasias of Group 3 than in Groups 1 or 2. The results indicated ethanol to exert weak promotion effects through cycline D1 overexpression on rat esophageal tumorigenesis initiated with NMBA.     

Inhibitory effects of 1,3-diaminopropane, an ornithine decarboxylase inhibitor, on rat two-stage urinary bladder carcinogenesis initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine

Overexpression of ornithine decarboxylase (ODC) has been shown to be characteristic of tumor development and progression in humans and experimental animals. Therefore, we have examined the effects of 1, 3-diaminopropane dihydrochloride (DAP), a potent inhibitor of ODC, on rat two-stage urinary bladder carcinogenesis initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). In experiment 1 (36 weeks), 6-week-old F344 male rats were administered 0.05% BBN in drinking water for 4 weeks and then divided into four groups. Animals of groups 1 and 2 received basal diet and drinking water supplemented with or without DAP (2 g/l). Groups 3 and 4 were given diet containing 5% sodium L-ascorbate (NaAsA), a typical urinary bladder tumor promoter, and drinking water with or without DAP. Administration of DAP to group 1 significantly reduced tumor size, multiplicity and incidence, particularly of papillomas, when compared with group 2 values. DAP together with NaAsA (group 3) also decreased tumor size relative to the group 4 case. To determine the effects of DAP on the early stages of bladder carcinogenesis and its mechanisms, a similar protocol was conducted (experiment 2) with death after 20 weeks. DAP treatment caused complete inhibition (0% incidence) of papillary and/or nodular hyperplasia in group 1 but was without influence in group 3, as compared with the respective controls. Moreover, the ODC activity, bromodeoxyuridine labeling indices and mRNA expression levels of cyclin D1 in the urinary bladder mucosa, determined by northern blotting, were markedly lower in group 1 than in group 2, but values were comparable for both groups administered NaAsA. Assessment of mRNA expression levels of the angiogenic vascular endothelial growth factor suggested no involvement in the inhibitory effects of DAP on urinary bladder carcinogenesis. The results indicate that inhibition of ODC could reduce urinary bladder carcinogenesis in rats, particularly in the early stages, through antiproliferative mechanisms.     

Gastrointestinal stromal tumor mimicking gynecological disease

Gastrointestinal stromal tumors (GISTs) are common mesenchymal tumors of the digestive tract. These tumors occasionally present a pelvic mass and leading to the misdiagnosis of gynecologic diseases. Two patients with GIST in the small intestine giving an impression of an ovarian fibroma and a uterine leiomyoma respectively were diagnosed correctly at the surgery. In the patients with a pelvic mass, especially if unusual symptoms and laboratory data being not compatible with gynecological disease, the possibility of diseases other than a gynecologic disease has to be considered.