Application of minimally invasive treatment for early gastric cancer

BACKGROUND AND OBJECTIVES: Although various types of minimally invasive treatment have emerged as the best front-line therapies for early gastric cancer (EGC), there have been no established indications that these attempts are applicable. The purpose of this study was to propose indications for the application of minimally invasive therapy for EGC. METHODS: A total of 566 patients with EGC who had undergone gastrectomy with D2 or more extended lymphadenectomy, from July 1993 to December 1997 were retrospectively analyzed. The risk factors that determine lymph node metastasis were investigated by univariate and multivariate analysis. RESULTS: The rate of lymph node metastasis was 11.8% for all EGC, 3.4% for mucosal cancer, and 21.0% for submucosal cancer. Lymph node metastasis was associated with submucosal invasion, larger tumor size, undifferentiated histology, and the presence of lymphatic or blood vessel invasion (LBVI) by univariate and multivariate analyses. When LBVI was absent, there was no lymph node metastasis if the tumor was smaller than 2.5 cm with differentiated histology, and smaller than 1.5 cm with undifferentiated histology, regardless of depth of invasion. Extra-perigastric lymph node metastases were noted in patients with submucosal tumors that have LBVI while none of mucosal cancer showed extra-perigastric lymph node metastases. CONCLUSIONS: Minimally invasive treatment can be possibly applied for patients with EGC using these four independent risk factors for lymph node metastasis in EGC. For mucosal cancers, EMR is indicated for EGCs without lymph node involvement based on tumor size and histology. When we found LBVI by pathologic examination after EMR, gastrectomy with D1 lymph node dissection is mandatory. For submucosal cancers, patients with small tumors could be treated with laparoscopic wedge resection without lymph node dissection. However, patients with larger sized tumors or tumors with LBVI should be treated with extended (D2) lymph node dissection.     

Synthetic and naturally occurring COX-2 inhibitors suppress proliferation in a human oesophageal adenocarcinoma cell line (OE33) by inducing apoptosis and cell cycle arrest

Epidemiological studies suggest that the use of NSAIDs and/or a high intake of fruit and vegetables reduce the risk of oesophageal adenocarcinoma. Since COX-2 is up-regulated in Barrett's oesophageal carcinogenesis, the protective effect of NSAIDs and natural food components might reflect COX-2 inhibition. We explored the effects of quercetin, a natural flavonoid with a potent COX-2 inhibitory activity, and two commercially available selective COX-2 inhibitors (NS-398 and nimesulide) on cell proliferation, apoptosis, PGE2 production and COX-2 mRNA expression in a human oesophageal adenocarcinoma cell line (OE33). Changes in the relative numbers of adherent and floating cells were quantified and apoptotic cells were identified using ethidium bromide and acridine orange staining under fluorescence microscopy. Flow cytometric analysis of adherent and floating cells was used to quantify apoptosis and to examine the effects of the agents on the cell cycle. After 48 h exposure at concentrations of > or =1 microM both COX-2 inhibitors and quercetin suppressed cell proliferation (P < 0.01) and increased the fraction of floating apoptotic cells. At higher concentrations (50 microM) and longer exposure (48 h) the effects of quercetin were significantly greater than those of the selective COX-2 inhibitors (P < 0.01). Cell cycle analyses showed that quercetin blocked cells in S phase, while the selective COX-2 inhibitors blocked cells in G1/S interphase. COX-2 mRNA expression was suppressed by quercetin and the synthetic COX-2 inhibitors in a time- and dose-dependent manner. Quercetin and the synthetic COX-2 inhibitors (10 microM) suppressed PGE2 production by approximately 70% after 24 h exposure (P < 0.001). We conclude that OE33 is a useful model for the study of COX-2 expression and associated phenomena in human adenocarcinoma cells. Synthetic COX-2 inhibitors and the food-borne flavonoid quercetin suppress proliferation, induce apoptosis and cell cycle block in human oesophageal adenocarcinoma cells in vitro, and future studies should assess their effects in vivo.     

Chemotherapy of small cell lung cancer: state of the art

PURPOSE OF REVIEW: Small cell lung cancer was termed chemosensitive with the introduction of combination chemotherapy in the 1970s. However, two decades of trials have seen little significant progress in achieving its "curable" potential. This paper presents an update of data recently published from phase 2 and phase 3 trials. RECENT FINDINGS: Platinum and etoposide combination chemotherapy remains the standard of care in small cell lung cancer. New agents, including irinotecan, may improve outcomes, but confirmatory trials are awaited. Triplet therapy, dose intensification, and maintenance therapy have not demonstrated meaningful survival improvements given the increased associated toxicity. Outcomes in limited-stage disease are optimized with the use of concurrent and early chemoradiation. New agents offering an improved toxicity profile for second-line therapy are emerging. SUMMARY: Small cell lung cancer remains an aggressive disease. Recent advances have yielded, at best, only modest gains. New strategies are required, including incorporation of novel targeted agents.     

What factors explain the number of physical therapy treatment sessions in patients referred with low back pain; a multilevel analysis

Background  

It is well-known that the number of physical therapy treatment sessions varies over treatment episodes. Information is lacking, however, on the source and explanation of the variation. The purposes of the current study are: 1) to determine how the variance in the number of physical therapy treatment sessions in patients with non-specific low back pain (LBP) in the Netherlands is distributed over patient level, therapist level and practice level; and 2) to determine the factors that explain the variance.     

Pallidal index on MRI as a target organ dose of manganese: structural equation model analysis

We have used a structural equation model (SEM) to analyze the interrelationships among exposure markers, magnetic resonance imaging (MRI) signal index, and neurobehavioral effects. Based on exposure groups, we assessed blood manganese, MRI measurements of pallidal index (PI), and neurobehavioral core test battery (WHO-NCTB) on 111 male workers occupationally exposed to manganese, including welders, smelter workers, and welding rod manufacturing workers. Latent variables were constructed to represent the neurobehavioral effects in an integrated way. The structural equation model revealed that airborne manganese and blood manganese contribute to PI significantly. Manganese exposure in the ambient air may lead to an increase in the internal dose, not only indirectly, by increasing blood manganese level, but also directly, independent of blood concentration. PI significantly contributed to a decrease in neurobehavioral test scores. We found that airborne manganese contributed to PI, and that PI is the most effective predictor of neurobehavioral performance, after adjusting for age and level of education. In conclusion, PI on MRI reflects target organ dose of occupational manganese exposure.     

MR findings in eosinophilic infiltration of the liver

OBJECTIVE: This study describes the findings of magnetic resonance imaging (MRI) of focal eosinophilic infiltration of the liver. METHODS: Contrast-enhanced MR images of 8 patients with focal hepatic eosinophilic infiltration were reviewed retrospectively. We evaluated the signal intensity of focal lesions in T1-weighted and T2-weighted images and the pattern of enhancement in a dynamic contrast study. RESULTS: A total 22 focal hepatic lesions were observed; the lesions were isointense (55%) or hypointense (45%) on T1-weighted images and isointense (14%) or hyperintense (86%) on T2-weighted images. The arterial phase of the contrast study revealed 11 hyperintense lesions (50%). During the portal and delayed phases, 18 (82%) and 17 lesions (77%) were hyperintense, respectively. CONCLUSION: The focal eosinophilic infiltrations showed homogeneous enhancement in the portal and delayed phases in the dynamic contrast MR study. These findings should help to distinguish focal eosinophilic infiltration, especially from metastasis in patients with malignancy.     

Identification of compounds that inhibit growth of 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine-resistant cancer cells

The dietary carcinogen 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) is a heterocyclic amine and is a common byproduct of cooked meat and fish. Although most cells undergo apoptosis when exposed to this mutagen, subsets develop resistance. Rather than die, these resistant cells persist and accumulate mutations, thereby driving tumorigenesis of exposed organs within the gastrointestinal tract. By applying a high-throughput cell-based screen of 32,000 small molecules, we have identified a family of compounds that specifically inhibit the growth of PhIP-resistant cancer cells. These compounds may prove useful for the treatment or prevention of gastrointestinal tumors arising after exposure to PhIP and related carcinogens.     

Continuous, noninvasive, and localized microvascular tissue oximetry using visible light spectroscopy

BACKGROUND: The authors evaluated the ability of visible light spectroscopy (VLS) oximetry to detect hypoxemia and ischemia in human and animal subjects. Unlike near-infrared spectroscopy or pulse oximetry (SpO2), VLS tissue oximetry uses shallow-penetrating visible light to measure microvascular hemoglobin oxygen saturation (StO2) in small, thin tissue volumes. METHODS: In pigs, StO2 was measured in muscle and enteric mucosa during normoxia, hypoxemia (SpO2 = 40-96%), and ischemia (occlusion, arrest). In patients, StO2 was measured in skin, muscle, and oral/enteric mucosa during normoxia, hypoxemia (SpO2 = 60-99%), and ischemia (occlusion, compression, ventricular fibrillation). RESULTS: In pigs, normoxic StO2 was 71 +/- 4% (mean +/- SD), without differences between sites, and decreased during hypoxemia (muscle, 11 +/- 6%; P < 0.001) and ischemia (colon, 31 +/- 11%; P < 0.001). In patients, mean normoxic StO2 ranged from 68 to 77% at different sites (733 measures, 111 subjects); for each noninvasive site except skin, variance between subjects was low (e.g., colon, 69% +/- 4%, 40 subjects; buccal, 77% +/- 3%, 21 subjects). During hypoxemia, StO2 correlated with SpO2 (animals, r2 = 0.98; humans, r2 = 0.87). During ischemia, StO2 initially decreased at -1.3 +/- 0.2%/s and decreased to zero in 3-9 min (r2 = 0.94). Ischemia was distinguished from normoxia and hypoxemia by a widened pulse/VLS saturation difference (Delta < 30% during normoxia or hypoxemia vs. Delta > 35% during ischemia). CONCLUSIONS: VLS oximetry provides a continuous, noninvasive, and localized measurement of the StO2, sensitive to hypoxemia, regional, and global ischemia. The reproducible and narrow StO2 normal range for oral/enteric mucosa supports use of this site as an accessible and reliable reference point for the VLS monitoring of systemic flow.