An increase of CA 19.9 as the first clinical sign of ileocecal valve metastasis from breast cancer

CASE REPORT: The case of a breast cancer patient with a progressive increase of CA 19.9 that indicated gastrointestinal metastasis is reported. After the observation of an increased CA 19.9 serum value (104.00; n.v. 0.0-37.00) a colonoscopy was performed. This examination showed the presence of an erythematous and granular zone near the ileocecal valve. Histological examination of biopsies taken during the colonoscopy revealed atypical monomorphic cells between the organoid pattern of the colon-type ducts. Immunohistochemical staining was positive for cytokeratin 7 and for estrogen receptors, consistent with metastatic epithelial malignancy. After eleven months, the patient presented with signs of intestinal obstruction, requiring an ileocolic bypass. At definitive histological examination, the tumor exhibited features of mammary metastases. CONCLUSION: This is the first report in the literature of an ileocecal valve metastasis from breast cancer diagnosed by an increase of CA 19.9, which is a marker of primary colorectal carcinoma.     

Molecularly guided therapy of neuroblastoma: a review of different approaches

Neuroblastoma (NB) is the most frequent extra-cranial solid tumor and the first cause of lethality in pre-school age children. NB accounts for 9-10% of pediatric tumors and affects more than ten thousand children a year. It originates from the sympathetic nervous system and is characterized by heterogeneous pathological and clinical presentation. Stage 4 NB represents approximately 50% of the cases and shows metastatic dissemination at onset; its prognosis is grim, with 20% of the patients surviving at 5 years from diagnosis in spite of aggressive chemotherapy with autologous hematopoietic stem cell support. Novel therapeutic strategies are urgently needed to improve the prognosis of stage 4 NB patients. Here we review the most promising approaches to NB treatment that have already reached clinical testing or have proved to be successful in preclinical models of the disease. All of these approaches are molecularly guided, since their rational development has benefited from the enormous amount of information on the biology of neuroblastoma gathered through molecular biology and genetics studies. The following topics are reviewed: MYCN oncogene amplification as parameter for therapeutic decision, minimal residual disease, immunotherapy, gene therapy, differentiation and apoptotic therapy, anti-angiogenic therapy, gene expression profiling as tool for generating novel therapeutic approaches. Although several efforts are still needed to reach a significant cure of patients with neuroblastoma, molecularly guided approaches have opened new ways to neuroblastoma treatment and can represent useful models for other cancers of either childhood or adulthood.     

Capecitabine and mitomycin C is an effective combination for anthracycline- and taxane-resistant metastatic breast cancer

Capecitabine is converted to 5-fluorouracil by thymidine phosphorylase, and mitomycin C is capable of upregulating the expression of thymidine phosphorylase suggesting a synergistic effect. Fifty-three patients (median age 62 years) with anthracycline- and taxane-resistant, metastatic breast cancer received mitomycin C 6 mg/m(2) on day 1, and capecitabine (Xeloda) 2,000 mg/m(2)/day from day 1 to day 14 with cycles repeated every 4 weeks. Overall, 77.4% had visceral metastases and 33 were pretreated with >/=3 chemotherapy lines. A median of 6 cycles were given (range 1-19) with a complete response observed in 2 patients (3.9%), partial response in 17 (33.3%) and stable disease in 19 (37.2%). Overall response rate was 37.2% (95% CI, 24.0-50.5%), with a median duration of 10.4 months. Median time to progression was 8.1 months and median survival was 17.4 months (1- and 2-year survival rates of 60 and 28%, respectively). Toxicity was mild. The most frequent grade 3/4 events were neutropenia (5.7% of patients), diarrhea (3.8%), and deep venous thrombosis (3.8%). Capecitabine plus mitomycin C may represent an effective and manageable treatment option for advanced breast cancer patients resistant to anthracyclines and taxanes. This approach provides an alternative for pretreated patients with advanced breast cancer.     

Action of tetrodotoxin on spontaneous electrical activity of some smooth muscle preparations

The action of tetrodotoxin (TTX) has been studied in different smooth muscle preparations by recording mechanical and extracellular electrical activities. TTX, although able to abolish nerve-mediated reflex excitation in the small intestine, induced spontaneous firing and segmental contractions in the circular muscle. In both the intestine and the renal pelvis, the effect of TTX was maintained after cholinoceptor and adrenoceptor blockade. The results could be interpreted as evidence that a neurogenic tonic inhibition, possibly not involving cholinergic or adrenergic mechanisms, is operative in the iileum, colon and renal pelvis, and seems to be mainly directed towards the circular musculature of the small intestine.     

Opinions and self-reported health status of Italians seeking homeopathic treatment

The use of homeopathy is increasing worldwide. This multi-centre cross-sectional study aims to describe the opinions and self-reported health status of a sample of Italian people seeking homeopathic care. A self-administered questionnaire including socio-demographic characteristics, knowledge and opinions about homeopathy, personal experience with homeopathy, and, self-reported health status (SF-12), was administered to a sample of people who had sought homeopathy. Of a possible 1229 individuals invited to participate, 1223 did so. The majority of the participants were female, young (mean age 42 years), well educated (mean 13 years of education). The reason for seeking care was for either physical or emotional conditions. Most participants had fair to good knowledge of homeopathy, and the self-experienced effect (subjective judgment on efficacy) was good regardless of the type of health condition reported. The Physical Component Summary (PCS-12) scores were similar to the general Italian population, but the Mental Component Summary (MCS-12) scores were lower in all relevant strata examined. This study provides information on the characteristics of people seeking homeopathic care, in particular the results of the SF-12 self-reported health status evaluation.     

Genomic aberrations in normal appearing mucosa fields distal from oral potentially malignant lesions

Objectives

Oral fields of visually normal and non-dysplastic mucosa (ODFs) may represent the precursors of oral potentially malignant lesions (OPMLs). Aim of the study was to provide new evidence for the concept of the ??field carcinogenesis?? model by comparing the ODF and OPML genomic aberration profiles obtained by high resolution DNA flow cytometry (hr DNA-FCM) and array-Comparative Genomic Hybridization (a-CGH). A second aim was to investigate if specific CGH aberrations were associated with DNA aneuploidy.

Methods

Nineteen patients with single OPMLs were recruited for the study. In parallel with obtaining samples of OPML tissue from 11 leukoplakias without dysplasia (nd-OPMLs) and 8 with dysplasia (d-OPMLs), we also obtained samples from distant ODFs. DNA aneuploid nuclei detected by hr DNA-FCM were physically separated, based on DNA content, from the DNA diploid components with a DNA-FCM-Sorter. These relatively pure subpopulations of epithelial nuclei were then submitted to DNA extraction and a-CGH for a genome-wide analysis of DNA copy number aberrations (CNAs).

Results

The frequencies of DNA aneuploidy (DI????1) among ODFs and OPMLs were respectively 5.3% and 32%. The DI aneuploid values of ODFs and nd-OPMLs were all near-diploid (DI????1 and DI????1.4), while for d-OPMLs were high-aneuploid (DI?>?1.4) in 40% of the cases. CNA averages were 1.9 in ODFs and 6.5 in OPMLs. The gain of the chromosomal region 20q13.33-qter was observed in 37% of both ODFs and corresponding OPMLs. Additional common regions included 7p22.2-pter, 11p15.5-pter and 16p13.3-pter where gains were observed. Furthermore, gains of 20q13.31?Cq13.33 and of 5p13.33-pter and loss of 9p21.3 were detected at high frequency (respectively, at 62.5%, 50% and 50%) only in d-OPMLs. In particular, loss at 9p21.3, gain at 5p13.33-pter and gain of 20q13.31?Cq13.33 were associated with DNA aneuploidy (p?=?0.00004; p?=?0.0005; p?=?0.01).

Conclusions

ODFs and OPMLs showed common CNAs in specific chromosomal regions suggesting that they may represent early events of the natural history of oral carcinogenesis according to the field effect cancerization and may contribute to the ODF-OPML transition. In addition, loss at 9p21.3 and gains at 5p13.33-pter and 20q13.31?Cq13.33 may contribute to DNA aneuploidization.