Multivariate analysis of histopathologic prognostic factors for invasive cervical cancer treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy

BACKGROUND: The aim of this study was to identify the independent histopathologic prognostic factors for patients with cervical carcinoma treated with radical hysterectomy including paraaortic lymphadenectomy. METHODS: A total of 187 patients with stage IB to IIB cervical carcinomas treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy were retrospectively analyzed. The median follow-up period was 83 months. Cox regression analysis was used to select independent prognostic factors. RESULTS: Using multivariate Cox regression analysis, lymph node (LN) status (negative vs. metastasis to pelvic nodes except for common iliac nodes vs. common iliac/paraaortic node metastasis), histopathologic parametrial invasion, lymph-vascular space invasion (LVSI), and histology of pure adenocarcinoma were found to be independently related to patients' poor survival. For patients who had a tumor histologically confined to the uterus and have neither parametrial invasion nor lymph node metastasis, LVSI was the most important prognostic factor, and histologic type, depth of cervical stromal invasion, and tumor size were not related to survival. The survival of patients with a tumor extending to parametrium or pelvic lymph node(s) was adversely affected by histology of pure adenocarcinoma. When the tumor extended to common iliac or paraaortic nodes, patients' survival became quite poor irrespective of LVSI or histologic type of pure adenocarcinoma. Patients' prognosis could be stratified into low risk (patients with a tumor confined to the uterus not associated with LVSI: n = 80), intermediate risk (patients with a tumor confined to the uterus associated with positive LVSI, and patients with squamous/adenosquamous carcinoma associated with pelvic lymph node metastasis or parametrial invasion: n = 86), and high risk (patients with pure adenocarcinoma associated with pelvic lymph node metastasis or parametrial invasion, and patients with common iliac/paraaortic node metastasis: n = 21) with an estimated 5-year survival rate of 100 +/- 0 (mean +/- SE)%, 85.5 +/- 3.9%, and 25.1 +/- 9.7%, respectively. CONCLUSIONS: LN status, parametrial invasion, LVSI, and histology of pure adenocarcinoma are important histopathologic prognostic factors of cervical carcinoma treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy. Prognosis for patients with cervical carcinoma may be stratified by combined analysis of these histopathologic prognostic factors. Postoperative therapy needs to be individualized according to these prognostic factors and validated for its efficacy using randomized clinical trials.     

IGF-related proteins at birth in a case of antenatally diagnosed Silver-Russell syndrome

We report here a case with severe intrauterine growth restriction from the first trimester and clinical features of Silver-Russell syndrome including microcephaly, low-set ear, atrial septum defect, ventricular septum defect, diaphragmatic relaxation, and rocker bottom feet. Silver-Russell syndrome is thought to result from deletion of the distal long arm of chromosome 15 on which the IGF-I receptor (IGF-IR) gene is located. We measured both the maternal and cord blood levels of GH, IGF-I, and IGF-binding protein and performed an immunohistochemical study of IGF-IR in the placenta to investigate whether these IGF-related proteins were affected in this patient. The hormonal level of these proteins did not significantly differ from normal neonates, and immunohistochemical analysis suggested IGF-IR protein levels in the placenta were comparable to normal term neonates. These results support the hypothesis that growth insufficiency could occur in patients with monosomy of the distal long arm of chromosome 15 and suggest a critical threshold for IGF-related fetal growth in early pregnancy.     

A case of successful management of maternal septic shock with multiple organ failure following amniocentesis at midgestation

Maternal sepsis is an unusual but catastrophic complication of amniocentesis. We report a case of successful treatment of maternal septic shock and multiple organ failure following amniocentesis at midgestation, possibly due to needle puncture of the sigmoid colon, which was tightly adherent to the anterior surface of the pregnant uterus.     

Validity of ultrasonograph muscle thickness measurements for estimating muscle volume of knee extensors in humans

This study aimed to investigate the suitability of using ultrasonograph muscle thickness (MT) measurements to estimate the muscle volume (MV) of the quadriceps femoris as an alternative approach to magnetic resonance imaging (MRI). The subjects were 46 men aged from 20 to 70 years who were randomly allocated to either a validation or a cross-validation group. In the validation group, multiple and simple regression equations, which used a set of MT values determined at mid-thigh and thigh length (l) and the product of π, (MT/2)², and l [π·(MT/2)²·l], respectively, as independent variables, were derived to estimate the MV measured by MRI. Because the two equations were cross-validated, the data from the two groups were pooled to generate the final prediction equations: MV (cm³)=(MT×311.732)+(l×53.346) –2058.529 as the multiple regression equation and MV (cm³)=[π·(MT/2)²·l]×1.1176+663.040 as the simple regression equation. In the multiple regression equation, MT explained 75% of the variation in the MV measured by MRI. The r ² and the standard error of the estimate (SEE) of the equations were 0.824 and 175.6 cm³ (10.6%), respectively, for the multiple regression equation and 0.829 and 173.7 cm³ (10.5%), respectively, for the simple regression equation. Thus, the present results indicate that ultrasonograph MT measurements at mid-thigh are useful for estimating the MV of knee extensors. However, the observed SEE values suggest that the prediction equation obtained in this study may be limited to population studies rather than individual assessments in longitudinal studies. Electronic Publication     

Advances in the development of a reliable assay for the measurement of stool decay-accelerating factor in the detection of colorectal cancer

We have previously shown that stool concentrations of decay-accelerating factor (DAF; CD55), a membrane-bound complement-regulatory protein, are significantly elevated in patients with colorectal cancer and that the measurement of stool DAF may be a valuable test for the detection of colorectal cancer. Accordingly, we are working to develop a clinically useful immunoassay for fecal DAF. A requirement for such assay is a plentiful and reliable supply of anti-DAF antibodies. We developed a sandwich enzyme-linked immunosorbent assay (ELISA) for DAF in stool specimens, using two monoclonal anti-DAF antibodies recognizing different epitopes on the DAF molecule. When we first used a biotin-labeled antibody and enzyme-linked streptavidin method, we often observed stool interference, probably due to the presence of a substance(s) with biotin activity which non-specifically bound to the Fc portion of IgG of the first anti-DAF antibody on the ELISA wells. By the use of inorganic salts in the sample-dilution buffer and HRP-labeled anti-DAF as second antibody, we circumvented the stool interference and established that the new ELISA system could reliably measure DAF at low concentrations in stool specimens. Because the new assay system uses only monoclonal antibodies, we can now consistently supply ample amounts of antibodies for routine measurement of stool DAF.     

The current status of structured treatment interruption

There is considerable interest in structured treatment interruption(STI), which has been stimulated by certain evidence that treatment interruption may boost the infected individual's immune response to HIV-1. There are several distinct settings where STI may be instituted: (i) STI for those with acute HIV-1 infection, (ii) STI for those with chronic infection, and (iii) STI before switching drugs. A number of STI protocols have been evaluated and certain promising results have been reported in certain groups of HIV-1-infected individuals while viral rebound as the consequence of interruption has been seen in other patients and drug failure to re-suppress HIV-1 upon re-starting therapy, STI-associated CD4+ cell decline and viral drug resistance emergence have been serious concern. Currently, STI cannot be recommended in clinical settings. Randomized, controlled trials to determine the applicability of STI for therapy of HIV-1 infection are required.     

Color Doppler ultrasonography: diagnosis of ectopic thyroid gland in patients with congenital hypothyroidism caused by thyroid dysgenesis

The etiology of congenital hypothyroidism (CH) may play an important role in determining disease severity, outcome, and, therefore, its treatment schedule. Radionuclide imaging (RI) is currently the most precise diagnostic technique to establish the etiology of CH. Conventional ultrasound can identify an athyrotic condition at the normal neck position and has gained acceptance for the initial evaluation of CH; however, its ability in delineating ectopic thyroid is limited. We used color Doppler ultrasonography (CDU) to assess blood flow and morphology in the detection of ectopic thyroid in 11 CH patients disclosed by neonatal screening; thyroid glands were undetectable at the normal location by gray-scale ultrasonography (GSU). The patients studied consisted of two infants for initial investigation and nine children for reevaluating the cause of CH. All of the patients underwent GSU, CDU, RI, and magnetic resonance imaging (MRI) investigation. We set RI as the defining diagnostic test for detecting ectopic thyroid and compared the imaging of CDU with those of GSU and MRI. The results of RI showed 10 ectopic thyroids and one athyreosis. In the patients with ectopic thyroid, the sensitivity of CDU, GSU, and MRI for detecting ectopic thyroid was 90, 70, and 70%, respectively. We conclude that CDU is superior to GSU and MRI for detecting ectopic thyroid and that CDU may be adopted as the diagnostic tool for the initial investigation of suspected CH.