Matrix metalloproteinases-2 and -9 in cervical cancer: different roles in tumor progression

The incidence of uterine cervical cancer has increased slightly in Western countries, with an increase in relatively young women. Overexpression of matrix metalloproteinases (MMPs)-2 and -9 has turned out as a prognostic factor in many cancers. We compared the expression of the proteins MMP-2 and MMP-9 in cervical primary tumors with clinical outcome and risk factors of cervical cancer. One hundred sixty-one patients with cervical cancer treated in Ume? University Hospital or Sahlgrenska University Hospital, Sweden, between 1991 and 1995 were included in the study. Paraffin-embedded tissue samples obtained prior to treatment were examined immunohistochemically by specific antibodies for MMP-2 and MMP-9. Forty-two percent of the tumors were intensively positive for MMP-2 and 31% for MMP-9. Nineteen percent of the samples were intensively positive for both proteinases and 47% negative or weak for both. Overexpression of MMP-2 seemed to predict unfavorable survival under Kaplan-Meier analysis and in the multivariate analysis. Early sexual activity and low parity seemed to correlate to overexpression of MMP-2. MMP-9 was not associated with survival or sexual behavior. Intensive MMP-9 was noted in grade 1 tumors. We conclude that MMP-2 and MMP-9 have different roles in uterine cervical cancer. MMP-2 could be associated with aggressive behavior, but MMP-9 expression diminishes in high-grade tumors.     

Predictability of retroperitoneal lymph node metastasis by using clinicopathologic variables in surgically staged endometrial cancer

The purpose of this study was to predict lymphatic involvement in endometrial cancer using clinicopathologic variables of patients treated with surgical staging. Overall, 461 patients treated with an initial surgical staging procedure including complete pelvic-para-aortic lymphadenectomy were included. The mean number of resected lymph nodes was 27 (median 26; range 15-83), and 54 patients (12%) had lymphatic involvement. Of these patients, 32 had only pelvic, 15 had both pelvic and para-aortic, and 7 had isolated para-aortic metastases. In the multivariate analysis, deep myometrial invasion (P= 0.02), lymphvascular space invasion (P= 0.001), positive peritoneal cytology (P= 0.002), and cervical involvement (P= 0.003) predicted retroperitoneal lymph node metastasis (RLN) significantly. Two hundred seventy-four patients (59.4%) had at least one of these poor prognostic factors identified by multivariate analysis. In this patient population, 53 (19.3%) had lymphatic involvement compared to 1 patient in the group of 187 patients with low-risk criteria. Ninety-eight percent of patients with RLN were predicted by this model, and with the advent of accurate diagnostic techniques, 40% of patients could be saved from undergoing lymphadenectomy.     

Familial risk assessment for early-onset coronary heart disease.

PURPOSE: We examined the performance of a familial risk assessment method that stratifies risk for early-onset coronary heart disease by considering the number of relatives with coronary disease, degree of relationship, lineage, and age at diagnosis. METHODS: By using data from the HealthStyles 2003 survey, we assessed the associations between familial risk and early-onset coronary heart disease, diabetes, hypercholesterolemia, hypertension, and obesity. By using area under the curve statistics, we evaluated the discriminatory ability of various risk assessment models. RESULTS: Of 4,035 respondents, 60% were female and 72% were white, with a mean age of 48.8 years. After adjustment for demographics, strong and moderate risk were significantly associated with approximately a five- and twofold risk of early-onset coronary disease, respectively. After adjustment for demographics and personal history of cardiovascular disease, strong familial risk was also significantly associated with diabetes, hypercholesterolemia, hypertension, and obesity. A risk assessment model that included familial risk, demographics, and personal history of diabetes, hypercholesterolemia, hypertension, and obesity was most optimal with an area under the curve statistic of 87.2% CONCLUSIONS: Familial risk assessment can stratify risk for early-onset coronary heart disease. Several conditions associated with increased familial risk can be prevented. These results have important implications for risk assessment and risk-reducing interventions.     

Complete maternal uniparental isodisomy of chromosome 4 in a subject with major depressive disorder detected by high density SNP genotyping arrays.

Uniparental isodisomy (iUPD) is a rare genetic condition caused by non-disjunction during meiosis that ultimately leads to a duplication of either the maternal or paternal chromosome in the affected individual. Two types of disorders can result, those due to imprinted genes and those due to homozygosity of recessive disease-causing mutations. Here, we describe the third known case of complete chromosome 4 iUPD of maternal origin. This condition became apparent during whole genome linkage studies of psychiatric disorders in the Portuguese population. The proband is an adult female with normal fertility and no major medical complaints, but a history of major depressive disorder and multiple suicide attempts. The proband's siblings and parents had normal chromosome 4 genotypes and no history of mood disturbance. A brief review of other studies lends support for the possibility that genes on chromosome 4 might confer risk for mood disorders. We conclude that chromosome 4 maternal uniparental disomy (UPD) is a rare disorder that may present with a major depressive phenotype. The lack of a common disease phenotype between this and two other cases of chromosome 4 iUPD [Lindenbaum et al. [1991] Am J Med Genet 49(Suppl 285):1582; Spena et al. [2004] Eur J Hum Genet 12:891-898) would suggest that there is no vital maternal gene imprinting on chromosome 4. However, since there is no reported case of paternal chromosome 4 UPD, paternal gene imprinting on chromosome 4 cannot be excluded.     

Female pelvic floor. Descriptive anatomy and clinical exploration by transvaginal ultrasound

In order to assess the state and pathology of the woman's pelvis minor, a number of methods are commonly used among practitioners, encompassing clinical exploration, radiology, MRN, urodynamics, endoscopy and echography.

Echography has been poorly used in clinical pelvic exploration and its reliability is actually a matter of controversy 1. However, echographic surveys can provide us with valuable gynecological data on the state and pathologies of the soft pelvis, within the genital regions or even going beyond them, i.e. the rectal channel, bladder, urethra, anus, vascular plexuses, and all of their supporting tissues.

At our research unit, we have been employing Transvaginal Ultrasound echography (TVU) for a long time in conjunction with other pelvis-focused methods in order to study different kinds of pelvic alterations. TVU has proven to be friendly to use, fast, harmless and inexpensive, allowing serial explorations and producing high-quality dynamic images (loop-cinema, video-tape). Furthermore, this method is fairly aseptic in that the occurrence of faeces in the rectal ampolla is not a nuisance but a bonus in tracking the contours of the rectum walls and other topographical features which would be otherwise difficult to survey.

A complete pelvic floor TVU may add no longer than 5-8 minutes to a routine gynecological examination, can be implemented by the general gynecologist and generates data that can be further studied by the appropriate specialist for a more insightful evaluation 2.     

Iron overload manifesting as apparent exacerbation of hepatic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

Iron overload presenting as exacerbation of hepatic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation has not been previously described. We report 6 patients with established hepatic GVHD in whom iron overload (median serum ferritin, 7231 mug/dL; median transferrin saturation, 77%) resulting from a lifetime median of 20 units of packed red blood cell transfusions was manifested by worsening of liver function. Liver biopsies performed in 4 patients confirmed severe iron overload and also hepatic GVHD. Analysis for the C282Y and H63D hemochromatosis gene mutation was negative for the homozygous state in all 6 patients. Erythropoietin-assisted phlebotomy resulted in normalization of liver function at a median of 7 months and of serum ferritin at a median of 11 months. Immunosuppressive therapy was successfully tapered in all 4 patients who completed the phlebotomy program, and this supported the impression that iron overload, rather than GVHD, was the principal cause of liver dysfunction. At a median follow-up of 50 months (range, 18-76 months) from the transplantation and 25 months (range, 5-36 months) from ferritin normalization, all 4 patients require maintenance phlebotomy. We conclude that iron overload can mimic GVHD exacerbation, thus resulting in unnecessary continuation or intensification of immunosuppressive therapy for GVHD, and that maintenance phlebotomy is necessary after successful iron-reduction therapy.