Detection of Lymphatic Micrometastases in Patients With Stages I and II Colorectal Cancer: Impact on Five-Year Survival

PURPOSE: Despite having removed the whole macroscopic disease (curative intent surgery), one of five patients with Stages I and II colorectal cancer will develop recurrence. Lymphatic micrometastases detected by immunohistochemistry could be one of explanation for recurrence and cancer-related death in patients without lymph node involvement at light microscopy. However, the biologic importance of micrometastases remains unclear. This study was designed to determine the impact of micrometastases in five-year survival in patients with Stages I and II colorectal cancer.METHODS: This retrospective study included patients operated on between May 1989 and January 1999 for colorectal cancer without histopathologic lymph node involvement. Patients who received any adjuvant therapy were excluded. Immunohistochemical staining of the lymph nodes was performed with antipancytokeratin antibodies. Follow-up data were obtained from the clinical database and death certificates. Survival was estimated by the Kaplan-Meier method and compared by the log-rank test.RESULTS: Micrometastases were observed in 26 of 90 patients (28.9 percent). The mean follow-up time was 90.7 (range, 11–160) months. Seventeen cancer-related deaths occurred during follow-up (18.9 percent), 6 of them in patients with micrometastases (23.1 percent) and 11 in patients without micrometastases (17.2 percent; P = 0.559). Cancer-specific five-year survival was 87 percent in the whole group and 81 percent in patients positive for micrometastases vs. 90 percent in negative patients (P = 0.489).CONCLUSIONS: The presence of micrometastases in patients with Stages I and II colorectal cancer seems not to have any impact on cancer-specific survival.Supported by the Apertus Research Program (Andromaco Pharmaceutical Company) and by The National Public Grant (FONDECYT #1000556).     

Acrylamide does not induce tumorigenesis or major defects in mice in vivo

Chronic administration of acrylamide has been shown to induce thyroid tumors in rat. In vitro acrylamide also causes DNA damage, as demonstrated by the comet assay, in various types of cells including human thyroid cells and lymphocytes, as well as rat thyroid cell lines. In this work, mice were administered acrylamide in their drinking water in doses comparable with those used in rats, i.e., around 3-4 mg/kg per day for mice treated 2, 6, and 8 months. Some of the mice were also treated with thyroxine (T(4)) to depress the activity of the thyroid. Others were treated with methimazole that inhibits thyroid hormone synthesis and consequently secretion and thus induces TSH secretion and thyroid activation. These moderate treatments were shown to have their known effect on the thyroid (e.g. thyroid hormone and thyrotropin serum levels, thyroid gland morphology...). Besides, T(4) induced an important polydipsia and degenerative hypertrophy of adrenal medulla. Acrylamide exerted various discrete effects and at high doses caused peripheral neuropathy, as demonstrated by hind-leg paralysis. However, it did not induce thyroid tumorigenesis. These results show that the thyroid tumorigenic effects of acrylamide are not observed in another rodent species, the mouse, and suggest the necessity of an epidemiological study in human to conclude on a public health policy.     

Nutzen der stationären Therapie in der Versorgung von Patienten mit Rheumatoider Arthritis

Our aim was to analyze the existing body of evidence about inpatient care of patients suffering from rheumatoid arthritis (RA). The report was induced by the executive board of the German Society of Rheumatology which assigned the "Oliver-Sangha committee" to dissect and point out the tasks of inpatient care during the next few years. A systemic search of the literature was performed covering the years 1966 to 2001. A total of 16 studies were selected and thoroughly appraised in a systematic way. Four randomized controlled trials addressing the question could be identified. All of them included only patients in a clinical condition allowing outpatient care as well. Two studies indicate some advantage of inpatient care in comparison to outpatient treatment. Two studies, both equivalence studies from design, reveal that RA patients do not generally experience additional benefit from hospitalization. Consideration of two additional cohort studies demonstrates the increased need of inpatient care in RA patients. None of the studies was derived from the German health care system. Emergency cases were not the subject of any of these trials. General statements about the value of inpatient care of RA patients can not be drawn from the analyzed studies. The committee makes suggestions for future investigations that may help to answer this important question considering the special circumstances of the German health care system.     

Phenotyping of malignant hematopoietic cells

Summary 1255 cases of leukemia-lymphoma were tested between 1972 and 1984 by multiple marker analysis. Routine leukemia phenotyping was performed using standard morphological and cytochemical techniques in combination with clinical and histo-pathological information; the main emphasis was put on immunological surface marker analysis using erythrocyte rosette assays, TdT and a large panel of poly- and monoclonal antibody tests. The 1255 cases were divided into these major types and subtypes: 349 cases of ALL and related immature T- and Burkitt-lymphomas (cALL, pre B-ALL, B-ALL and Burkitt-lymphomas, T-ALL and immature, mostly leukemic T-lymphomas, Null-ALL), 454 cases of mature T- and B-cell malignancies (T-CLL, mycosis fungoides, Sezary-syndrome, T-lymphomas, B-CLL, hairy cell leukemia, multiple myeloma, B-lymphomas), 263 cases of acute myeloid leukemias (AML, AMMoL/AMoL), 182 cases of chronic myeloid leukemias (CML in chronic phase, CMoL, CML in blast crisis), 6 cases of erythroleukemia and 1 case of megakaryoblastic leukemia. A simplified classification scheme which has been used in our laboratories is presented. Phenotyping is of diagnostic, prognostic and therapeutic relevance, most evidently for patients with ALL. Routine leukemia phenotyping should be performed with highly standardized techniques and reagents and by combining information from several fields in the multiple marker analysis. New areas of leukemia research might become very useful for the routine procedure of phenotyping.Abbreviations ALL acute lymphoblastic leukemia - AML acute myeloblastic leukemia - AMMoL acute myelomonoblastic leukemia - AMoL acute monoblastic leukemia - cALL common ALL - CLL chronic lymphocytic leukemia - CML chronic myelocytic leukemia - CML-BC CML in blastic crisis - CMoL chronic monocytic leukemia     

STAT3 is required for IL-21-induced secretion of IgE from human naive B cells

The production of immunoglobulin E (IgE) is tightly regulated. This is evidenced by the fact that it comprises less than 0.0001% of serum Ig, and aberrant production causes atopic conditions, including allergy, rhinitis, and anaphylaxis. Interleukin-4 (IL-4) is a well-characterized inducer of IgE by human and murine B cells, whereas interferon-gamma can antagonize this effect. IL-21 has also been recognized for its ability to suppress IL-4-induced IgE production by murine B cells. Here, we identified IL-21 as an inducer of IgE production by CD40L-stimulated human naive B cells. Furthermore, there was a striking synergy between IL-4 and IL-21 on inducing IgE secretion by CD40L-stimulated human B cells, such that the levels detected under these conditions exceeded those induced by IL-4 or IL-21 alone by more than 10-fold. IL-21 induced activation of STAT3 and analysis of B cells from patients with loss-of-function STAT3 mutations revealed that the ability of IL-21 to induce IgE secretion, and augment that driven by IL-4, was STAT3-dependent. These findings highlight a fundamental difference between the regulation of IgE production by human and murine B cells and have implications for the dysregulated production of IgE in conditions characterized by extremely high levels of serum IgE.     

Feeding sources and trypanosome infection index of Rhodnius pallescens in a Chagas disease endemic area of Amador County, Panama

The sylvatic triatomine Rhodnius pallescens is considered to be the most important and widespread vector of Trypanosoma cruzi and Trypanosoma rangeli in Panama. However, its behavior and biological characteristics have only been partially investigated. Thus, to achieve sustainable and efficient control over Chagas disease in Panama, a better understanding of the ecology and biology of R. pallescens is essential. In this study we evaluated R. pallescens host feeding sources using a dot-blot assay, and the trypanosome infection index by PCR analysis in a Chagas disease endemic area of central Panama. It was found that in peridomestic palm trees, 20.3% of the examined bugs had fed on opossums (Didelphis marsupialis). However, we observed an increased anthropophagy (25.4%) for those bugs collected inside houses. Considering the domestic and peridomestic habitats as a whole, the proportion of collected R. pallescens infected with trypanosomes was 87.4%. In the two habitats the predominant infection was with T. cruzi (80-90%). Between 47-51% of the analyzed triatomines were infected with T. rangeli. Mixed infections (40-51%) were also detected. These findings provide a better basis for the implementation of a rational control and surveillance program for Chagas disease in regions where R. pallescens is endemic.     

Comparison of the grading of esophageal varices by transnasal endoluminal ultrasound and esophagogastroduodenoscopy.

BACKGROUND & AIMS: Esophagogastroduodenoscopy (EGD) is the current standard for evaluating esophageal varices, yet there is no universally accepted system of grading varices endoscopically and several studies have shown interobserver variability of endoscopic grading. High-resolution endoluminal ultrasound 20 MHz (HRES) has been shown to detect varices accurately and can be performed without sedation. Our aim was to compare the detection of esophageal varices by transnasal HRES and EGD. METHODS: We prospectively studied 37 cirrhotic patients being evaluated for esophageal varices. HRES was used to measure the largest esophageal variceal diameter and then EGD was performed. Photographs were taken for both procedures. Three blinded investigators graded the EGD photographs at 2 periods. End points were as follows: (1) the correlation of HRES variceal diameter and EGD grading of varices, and (2) the assessment of interobserver and intraobserver variation in varix grading by EGD. RESULTS: The correlation between the transnasal HRES and EGD was .63, with a 95% confidence interval of .37-.80. The HRES detected early varices that were not seen by EGD. The interobserver correlation for EGD scoring was .87 or greater in all comparisons and the intraobserver correlation was .91 or greater. CONCLUSIONS: In conclusion, there is a significant correlation between transnasal HRES size measurement of esophageal varices and EGD. HRES is much more sensitive in detecting early esophageal varices and may not require sedation, suggesting that it may be more tolerable to patients and is worth further study.