Evolution of liver disease in morbid obesity after small-intestinal bypass and its restoration. A case report

We studied a woman who underwent a jejunoileal bypass for the treatment of morbid obesity and in whom severe jaundice and hepatic failure developed six months later; these developments prompted restoration of the normal continuity of the small bowel. Four serial wedge biopsy specimens of the liver were taken during a three-year follow-up. The first biopsy was performed before the bypass surgery, the second six months after the operation, the third three months after restoration of normal continuity of the bowel, and the fourth three years later. The biopsy specimens clearly showed the morphologic changes of the liver in obesity, the effect of small intestinal bypass and its reversal on hepatic structure, and the natural evolution of liver disease in morbid obesity.     

Depth of cervical stromal invasion as a prognostic factor after radical surgery for early stage cervical cancer

INTRODUCTION: In the United Kingdom, the Royal College of Pathologists have issued guidelines detailing how the depth of stromal invasion (DOI) in cervical cancer should be measured as a percentage of the overall cervical radius in millimeters. Several studies have found the assessment of the depth of stromal invasion by cancer of the cervix to be of prognostic value. These studies did not take into account patients whose diagnostic procedures required removal of much tumor (large loop excision of the transformation zone [LLETZ] and knife cone biopsies). Furthermore, the Royal College of Pathologists guidelines do not address this issue. MATERIALS AND METHODS: Over the period of 6 years, 228 women had radical hysterectomy (RH) for stage Ib/IIa cervical cancer. The percentage of the depth of stromal invasion was measured according to the Royal College of Pathologist's guidelines in the UK. Patients who had large loop excision of the transformation zone and knife cone biopsies were excluded (91 patients). RESULTS: A Cox regression analysis showed that when nodal involvement, depth of stromal invasion, endothelial lined space invasion (ELSI), and tumor type were fitted simultaneously, only nodal involvement remained as a marker of adverse outcome. CONCLUSIONS: We recommend that when the DOI is measured, account should be taken of the LLETZ/knife cone biopsy size. A randomized controlled trial, which concludes that DOI is an independent prognostic factor, is needed. Until this is properly evaluated, we feel that including DOI as an essential part of the standard pathological report is not warranted.     

In vitro and in vivo activity of the maytansinoid immunoconjugate huN901-N2'-deacetyl-N2'-(3-mercapto-1-oxopropyl)-maytansine against CD56+ multiple myeloma cells

HuN901 is a humanized monoclonal antibody that binds with high affinity to CD56, the neuronal cell adhesion molecule. HuN901 conjugated with the maytansinoid N(2')-deacetyl-N(2')-(3-mercapto-1-oxopropyl)-maytansine (DM1), a potent antimicrotubular cytotoxic agent, may provide targeted delivery of the drug to CD56 expressing tumors. Based on gene expression profiles of primary multiple myeloma (MM) cells showing expression of CD56 in 10 out of 15 patients (66.6%) and flow cytometric profiles of MM (CD38(bright)CD45(lo)) cells showing CD56 expression in 22 out of 28 patients (79%), we assessed the efficacy of huN901-DM1 for the treatment of MM. We first examined the in vitro cytotoxicity and specificity of huN901-DM1 on a panel of CD56(+) and CD56(-) MM cell lines, as well as a CD56(-) Waldenstrom's macroglobulinemia cell line. HuN901-DM1 treatment selectively decreased survival of CD56(+) MM cell lines and depleted CD56(+) MM cells from mixed cultures with a CD56(-) cell line or adherent bone marrow stromal cells. In vivo antitumor activity of huN901-DM1 was then studied in a tumor xenograft model using a CD56(+) OPM2 human MM cell line in SCID mice. We observed inhibition of serum paraprotein secretion, inhibition of tumor growth, and increase in survival of mice treated with huN901-DM1. Our data therefore demonstrate that huN901-DM1 has significant in vitro and in vivo antimyeloma activity at doses that are well tolerated in a murine model. Taken together, these data provide the framework for clinical trials of this agent to improve patient outcome in MM.     

Role of tumour necrosis factor gene polymorphisms (-308 and -238) in breast cancer susceptibility and severity

Introduction  

Genetic polymorphisms in the promoter region of the tumour necrosis factor (TNF) gene can regulate gene expression and have been associated with inflammatory and malignant conditions. We have investigated two polymorphisms in the promoter of the TNF gene (-308 G>A and -238 G>A) for their role in breast cancer susceptibility and severity by means of an allelic association study.     

Assessment of carcinogenicity, using PAH-DNA adducts, in workers exposed to polycyclic aromatic hydrocarbons

Introduction

Polycyclic aromatic hydrocarbons (PAH) are environmental contaminants that have been of interest in cancer research for a considerable length of time. DNA adduct formation is considered a marker and indicator for exposure to PAH. The aim of this study was to determine PAH-DNA adduct levels in peripheral blood lymphocytes and urine obtained from workers exposed to PAH, and to evaluate tobacco use, GSTM1 and GSTT1 as possible contributory risk factors.

Material and methods

Our study included a random sample of 66 workers exposed to PAH and 49 non-exposed workers.

Results

PAH-DNA adduct levels of exposed workers were lower than that of the non-exposed group (p<0.05). However, current smoking, GSTM1-negatives, and current smoking with GSTM1-negatives were more frequent in the non-exposed group. In addition, non-exposed workers reported exposure to PAH in their current jobs, as compared with the exposed group (p<0.001). Linear regression analysis identified the levels of benzo-[b]-fluoranthene in the working area as the only significant DNA adduct-forming risk factor (p=0.025).

Conclusion

Further research, with an appropriately large sample size, is highly recommended in measuring PAH-DNA adduct levels and evaluating their relationship with the different types of PAH.