A genome search for primary vesicoureteral reflux shows further evidence for genetic heterogeneity

Vesicoureteral reflux (VUR) is the most common disease of the urinary tract in children. In order to identify gene(s) involved in this complex disorder, we performed a genome-wide search in a selected sample of 31 patients with primary VUR from eight families originating from southern Italy. Sixteen additional families with 41 patients were included in a second stage. Nonparametric, affected-only linkage analysis identified four genomic areas on chromosomes 1, 3, and 4 (p < 0.05); the best result corresponded to the D3S3681-D3S1569 interval on chromosome 3 (nonparametric linkage score, NPL = 2.75, p = 0.008). This region was then saturated with 26 additional markers, tested in the complete group of 72 patients from 24 families (NPL = 2.01, p = 0.01). We identified a genomic area on 3q22.2-23, where 26 patients from six multiplex families shared overlapping haplotypes. However, we did not find evidence for a common ancestral haplotype. The region on chromosome 1 was delimited to 1p36.2-34.3 (D1S228-D1S255, max. NPL = 1.70, p = 0.03), after additional fine typing. Furthermore, on chromosome 22q11.22-12.3, patients from a single family showed excess allele sharing (NPL = 3.35, p = 0.015). Only the chromosome 3q region has been previously reported in the single genome-wide screening available for primary VUR. Our results suggest the presence of several novel loci for primary VUR, giving further evidence for the genetic heterogeneity of this disorder

Nuclear medicine in diagnosis, staging and follow-up of thyroid cancer

Diagnostic strategy in thyroid cancer is conditioned by epidemiological, pathophysiological, cost-effective issues changing with age and countries. Nuclear medicine has a role mainly in differentiated carcinomas, i.e. in the large majority of thyroid cancers. In diagnosis of thyroid nodule 99mTc-perthecnetate is indicated in patients with low TSH levels, multinodular goiter, solid nodules at US negative at FNA. Radiolabeled somatostatin analogs or Metaiodobenzylguanidine (MIBG) can be used in suspicion of medullary carcinoma. There is no role in staging. WBS with 131I has a role after surgical resection of the thyroid gland and it is no more suggested before ablative therapy, because of the possible stunning effect. In the follow-up thyroglobulin (Tg) test is mandatory both after therapy withdrawal or after rhTSH administration. Some authors already suggest to use this test alone, as 1st step, in patients with differentiated carcinoma at low risk of recurrence, but this approach is not yet generally accepted and it has not yet been validated in tumors at intermediate/high risk. WBS with 131I is ever indicated when autoantibodies can affect reliability of Tg values and in presence of high Tg levels to better define a radiometabolic therapy. In case of negative WBS, PETFDG can be proposed. In WBS, 123I can be an alternative to 131I , but it is not yet generally accepted mainly because of its higher costs. The clinical use of rhTSH to increase accuracy both of Tg and WBS can be already accepted in patients at high risk following hypothyroidism, with a worst prognosis or a low pituitary response

Blood pressure and cardiovascular involvement in children with neurofibromatosis type1.

We evaluated blood pressure in a sample of patients with neurofibromatosis type 1 (NF1), using ambulatory blood pressure monitoring (ABPM), to determine whether ABPM, when compared with casual BP recordings, allowed the detection of a higher risk for hypertension. We also evaluated the correlation between BP and vascular abnormalities. We studied 69 NF1 patients (36 males and 33 females) with a mean age of 11+/-4 years, divided into group A, with 24-h mean systolic blood pressure (SBP) or diastolic blood pressure (DBP) <95th percentile, and group B, with mean SBP or DBP >95th percentile. Standard electrocardiography and Mmode, two-dimensional echocardiography were performed and all patients were in sinus rhythm. ABPM identified 11 hypertensive patients (16%); 5 had a mean SBP >95th percentile, 3 mean SBP*DBP >95th percentile, and 3 a mean DBP >95th percentile. Laboratory and other investigations to exclude secondary hypertension were normal. Cardiac abnormalities were found in 13 of the 69 patients (18.8%) with NF1. There were no significant clinical and cardiac differences between the normotensive and hypertensive group. Our data emphasize the importance of periodic ABPM in NF1 patients to diagnose hypertension early and avoid target organ damage and increased mortality

Preliminary experiences in radioimmunoguided surgery for primary lung neoplasms

Background. Radioimmunoguided surgery (RIGS) can be a valid option in the management of lung cancer as well as neoplasms in other anatomic sites. Methods. We evaluated the usefulness of radioimmunoguided surgery (RIGS) in the staging of primitive non small cell lung cancer. Intraoperatively, this technique can define the lymph nodes involvement and thus, the radicality of the resection. In the first stage of our study, we looked for the epitope TAG 72 in 45 patients with primary non small cell lung cancer. The epitope was found by immunochemistry in only 6 cases. The only one operable patient was injected with monoclonal antibody B 72.3, that was125I-labelled. Results. At the operation, the monoclonal antibody showed no selectivity for neoplastic cells. Neoplastic tissue and healthy tissue showed a similar detection of the monoclonal antibody both intraoperatively and at the histochemical study. Because of the problems related with this method - e.g. technical difficulties, excessive wasting of time and lack of imaging - we modified our strategy. In this second stage of our study we used fragments of murine anti-CEA monoclonal antibody F023C5. The protocol was performed in 11 patients with squamous cell lung cancer. In one patient operated on for an excavated cancer (not well-defined at the immunoscintigraphy) intraoperative detection was negative while the ex vivo counts were significant: the neoplastic tissue showed a radioactivity twice higher than healthy tissue. Furthermore, the RIGS found a small intraparenchimal lymph node that was seen neither by CT nor by immunoscintigraphy. Conclusions. Our data are still preliminary, but with improvement of the technique and the use of more specific monoclonal antibodies the RIGS could become a helpful method, able to improve the radicality of surgery for lung cancer

Modulation of the axillary lymph node dissection in breast cancer

Molti studi hanno dimostrato la affidabilità della tecnica del linfonodo sentinella (SN) nella valutazione del parametro N nel cancro mammario tanto da indurre a limitare la dissezione ascellare alla biopsia del solo SN (SNB) in caso questo sia negativo. Dopo un periodo di messa a punto della tecnica di identificazione, biopsia ed esame istologico del SN (ottobre 97- gennaio 98) sempre seguita dalla dissezione completa dei tre livelli dell’ascella (ALND), abbiamo intrapreso uno studio per valutare la affidabilità di una dissezione limitata al solo I livello dell’ascella (FLND) in donne con T<3 cm, N0-1a, M0, non sottoposte in precedenza a trattamenti neoadiuvanti ed in cui il SN risultava non metastatico. Questa fase dello studio iniziata a febbraio 1998 si è conclusa a maggio 2001. Nel presente lavoro vengono riportati i risultati relativi a questo periodo. Materiali e metodi: abbiamo arruolato 256 donne con T <3cm, N0-1a, M0. La tecnica di rilievo del SN è stata in 49 casi con colorante vitale, in 23 con colorante + chirurgia radioguidata (RGS) e in 184 con la sola RGS. L’esame istologico estemporaneo del SN è stato eseguito con sezioni seriate sottili, colorate con EE, al congelatore. Nel caso in cui il SN risultava negativo all’esame intraoperatorio, abbiamo limitato la dissezione al solo I livello della ascella tranne che in 3 pazienti, con SN localizzato al II livello, in cui abbiamo effettuato una ALND. La FLND è stata eseguita in 17 casi con tecnica miniinvasiva. L’esame istologico definitivo del SN ha sempre compreso la immunoistochimica. Nel caso in cui l’esame definitivo mostrava una positività del SN, misconosciuta all’esame intraoperatorio, le pazienti sono state sottoposte a chemioterapia adiuvante. Risultati: Alla linfoscintigrafia preoperatoria il SN è stato evidenziato in 203/207 pazienti (98,1%). All’intervento chirurgico il SN è stato identificato in 46/49 (94%) con il colorante vitale, in 22/23 (96%) con la combinazione colorante + RGS e in 176/179 (98,3%) con la RGS. All’estemporanea è risultato negativo in 140, metastatico in 101; all’istologico definitivo abbiamo rilevato 6 falsi negativi del SN per positività di altri non SN (4 casi) o per evidenza alla immunoistochimica di micrometastasi del SN, non rilevate all’estemporanea (2 casi). Su 107 casi di N+ il SN era l’unico metastatico in 42 (39,3%). La percentuale di falsi negativi è risultata pari al 5,6% e la accuratezza diagnostica della SNB al 97,5%. Nel gruppo di pazienti trattate con FLND abbiamo rilevato solo due casi di linfedema di lieve entità (1,4%). Conclusioni: I nostri risultatisono in linea con la letteratura internazionale e ci hanno indotto, da giugno 2001, ad iniziare una nuova fase dello studio in cui, nelle donne con carcinoma mammario T1, limitiamo la dissezione dell’ascella al solo SN, se non metastatico.Several studies showed the reliability of the sentinel lymph node (SN) technique in the evaluation of the N parameter in breast cancer so much to induce surgeons to limit the axillary dissection to the biopsy of the SN alone (SNB) in case this is negative to the extemporaneous examination. After a period of focusing on the identification technique, biopsy and histological examination of the SN (October 97 - January 98) always followed by a complete dissection of the three axillary node levels (ALND), we started a study to evaluate the reliability of a limited dissection of the 1st level of the axilla (FLND) in women with T <3cm, NO-1a, MO, that did not undergo any neoadjuvant treatment and in which the SN resulted free from metastases. We started this phase of the study in February 1998 till May 2001. In the present paper we show the results related to this period. Materials and Methods: we enrolled 256 women with T <3cm, NO-la, MO. In 49 cases we used vital dye, in 23 dye + radioguided surgery (RGS) and in 184 RGS only. The extemporaneous histological examination of the SN has been performed with thin sections, dyed with EE. When SN was negative to the intraoperative examination, we limited the dissection to the 1st level of the axilla, except that in 3 patients, with SN located to the 2nd level, in which we did an ALND. The FLND has been performed in 17 cases with a minimally invasive technique. The definitive histological examination of the SN always included the immunohistochemistry. If the SN was positive, usually underestimated to the intraoperative examination, the patients had an adjuvant chemotherapy. Results: In 203/207 patients (98,1%) SN was found to the pre-operative lymphoscintigraphy. During surgery the SN was identified in 46/49 (94%) using the vital dye, in 22/23 (96%) using the vital dye + RGS and in 176/179 (98,3%) using RGS. To the extemporaneous histological examination SN was negative in 140, metastatic in 101; to the histological definitive results of the SN we noticed 6 false negative, since others lymph nodes than SN were positive (4 cases) or for evidence of micrometastases at the immunohistochemistry which were not detected at the extemporaneous examination (2 cases). On 107 cases of N+ the SN was the only metastatic lymph node in 42 (39,3%). The false negative percentage was 5,6% and the diagnostic accuracy of the SNB was 97,5%. In the group treated with FLND we only noticed two cases of light lymphedema (1,4%). Conclusions: Our results are in concordance with the international literature and they induced us, from June 2001, to begin a new phase of the study in which we limit the dissection of the axilla to the SN only, if not metastatic, in women with Tl breast carcinoma