The brisk-standing-test for long QT syndrome in prepubertal school children: defining normal.

Aims: Long QT syndrome (LQTS) is associated with malignant arrhythmias and sudden death from birth to advanced age. Prolongation of the QT-interval, may however be concealed on standard electrocardiograms (ECG). The brisk-standing-test (BST) was developed to guide LQTS-diagnosis and treatment in adults. We hypothesized that the BST may be used in prepubertal children to identify LQTS subjects. Accordingly, reference values for the BST should be available to prevent incorrect diagnosis and treatment of LQTS. In this study, we aim to present reference values for prepubertal children. Methods and results: Healthy, prepubertal children, aged 7-13 years underwent a standard supine resting ECG and during continuous ECG recording performed a BST. The QT-interval and heart rate corrected QTc were measured during the different BST stages. Fifty-seven children, 29 boys (10.2 ± 1.1 years) and 28 girls (9.9 ± 1.1 years) were included. Baseline characteristics and response to standing were not statistically different for boys and girls: mean supine pre-standing heart rate 74 ± 9 vs. 77 ± 9 bpm, supine pre-standing QTc 406 ± 27 vs. 407 ± 17 ms, maximal heart rate upon standing 109 ± 11 vs. 112 ± 11 bpm, and QTc at maximal heart rate 484 ± 29 vs. 487 ± 35 ms. The QT interval corrected for heart rate-prolongation at maximal tachycardia after standing was 79 ± 26 (19-144) ms, which is significantly longer than previously published values in adults (50± 30 ms). Conclusions: The QT interval corrected for heart rate prolongation after brisk standing in healthy prepubertal children is more pronounced than in healthy adults. This finding advocates distinct prepubertal cut-off values because using adult values for prepubertal children would yield false positive results with the risk of incorrect LQTS-diagnosis and overtreatment.

Left ventricular dysfunction is associated with frequent premature ventricular complexes and asymptomatic ventricular tachycardia in children.

AIMS: To assess the risk factors for left ventricular (LV) dysfunction in a paediatric population with idiopathic frequent premature ventricular contractions (PVCs) and asymptomatic ventricular tachycardias (VTs). METHODS AND RESULTS: Paediatric patients with the diagnosis of idiopathic frequent PVCs and asymptomatic VTs were retrospectively evaluated. Frequent PVCs were defined as ≥5% on 24 h Holter recording. Left ventricular dysfunction was defined as a shortening fraction of ≤28%. Seventy-two children were identified. Six patients showed LV dysfunction at diagnosis [age 10 ± 7 years, 2 (33%) had symptoms such as syncope, palpitations, fatigue, and dizziness], and 66 showed normal LV function [age 8 ± 6 years, 22 (33%) with symptoms]. Patients with LV dysfunction had a higher percentage of PVCs on Holter recordings (47 ± 16 vs. 16 ± 11%, P = 0.006), higher prevalence of VT [5 (83%) vs. 27 (41%), P = 0.045] and sustained ventricular tachycardia (sVT) [3 (50%) vs. 4 (6%), P = 0.001], and a higher number of couplets [6 (100%) vs. 34 (52%), P = 0.030]. In patients with LV dysfunction, two responded to medication (Classes Ic and II) and five underwent ablation, of which one was unsuccessful. During follow-up, LV function normalized in five of six patients. In patients with a normal function, none developed LV dysfunction during the follow-up. CONCLUSION: In children with idiopathic PVCs and asymptomatic VTs, development of LV dysfunction is associated with a higher burden of PVCs, the presence of sVTs, and couplets. Left ventricular dysfunction appears to be reversible if the burden of PVCs is decreased by medication or ablation.

[Not Available]. / Een neonaat met een strakke huid.

A newborn had a tight, dry skin with multiple fissures, an eclabium and ectropion. Breathing was compromised and regulation of body temperature was impaired. We described the patient as a 'collodion baby'. After genetic investigation the diagnosis congenital ichtyosis, recessive type 1 was made. At 12 months of age, the skin symptoms were significantly diminished.

p53 but not bcl-2 immunostaining is predictive of poor clinical complete response to primary chemotherapy in breast cancer patients.

Preoperative chemotherapy administered to breast cancer (BC) patients is a model for studying in vivo the interaction between cytotoxic treatment and clinical and biological parameters. Apoptosis induced by anticancer agents is a mechanism of treatment activity; therefore, overexpression of genes inhibiting the apoptotic pathway could produce drug resistant tumors. In the present study, the two most studied inhibitors of apoptosis, the bcl-2 gene and the mutant p53, have been evaluated to assess whether they may play a role in modulating response of BC to primary chemotherapy. From August 1990 to January 1997, 143 patients bearing T(2-4)N(0-1)M0 primary BC were submitted to two different chemotherapeutic regimens before surgery. The first 64 received the cyclophosphamide, methotrexate, 5-fluorouracil (CMF) regimen (on days 1 and 8 and every 28 days thereafter) associated with tamoxifen (30 mg daily) in case of estrogen receptor (ER)-positive BC, and the remaining 79 were submitted to single agent epirubicin (120 mg/m2 every 21 days). The expression of p53, bcl-2, Ki67, ER, progesterone receptor, c-erbB2, and the multidrug resistance P-glycoprotein (gp-170) was evaluated in BC specimens obtained at diagnosis by incision biopsy and at postchemotherapy surgery. At the end of chemotherapy administration (median, 3 cycles; range, 2-6), the clinical complete response (cCR) rate was superimposable in the patient subgroups with bcl-2-positive or -negative primary tumors; conversely, p53 expression, at a cutoff of 10% positive cells, was significantly associated with a lower cCR rate (9.4 versus 27.0%; P < 0.04). p53 was a significant predictor for poor cCR in the subset submitted to epirubicin (3.6 versus 25.5%; P < 0.02; in patients with p53+ and p53- BC, respectively); by contrast, only a trend toward lower cCR has been observed in patients with p53+ tumors receiving CMF +/- tamoxifen with respect to p53- ones. The distribution of cCR according to the gp-170-positive or -negative tumors was 8 versus 22% in patients submitted to epirubicin and 29 versus 30% in those receiving CMF +/- tamoxifen, respectively. In a multivariate regression analysis, after adjusting for treatment administered (epirubicin versus CMF +/- tamoxifen), menopausal status, tumor and node status, histology grade, ER, progesterone receptor, c-erbB2, Ki67, bcl-2, and gp-170 expression, the p53 status maintained an independent predictive role for cCR. Most of the tumors undergoing change in percentage of p53 expression after both treatments originally harbored mutant protein, and only four BC specimens that were p53 negative before chemotherapy became positive afterward. These data confirm in vivo the concept that the responsiveness of tumors to chemotherapy in part derives from the capability of BC cells to undergo apoptosis. The role of mutated p53 in preventing response is more evident in patients submitted to epirubicin, and this may be caused by the up-regulation of multidrug resistance gene expression by p53 inactivation. p53 is a stable phenotype and is not inducible by at least three or four chemotherapy cycles.

Monitoring surgical treatment of screen-detected breast lesions in Italy.

The object of this study was to assess quality of care and adherence to treatment guidelines of screen-detected lesions in Italy using a new audit system. Data on screen-detected cases surgically treated in 1997 were collected using a system (QT 2.3) developed within the Italian Group for Planning and Evaluating Mammographic Screening Programmes (GISMa) and the European Breast Cancer Screening Network. Results of 18 performance parameters were considered compared with the reference standards. In 1997, 515 lesions (335 invasive, 60 in situ and 120 benign) in 496 patients were collected from 14 departments in the Central and Northern area of Italy. The 18 indicators were analysed and grouped according to six quality objectives. Some results were good and others were excellent, such as intraoperative identification, breast conservation surgery, adequate axillary procedures and completeness of pathology reports, but most of them failed: waiting times, preoperative diagnosis, employment of frozen section on small lesions and avoiding axillary procedures in ductal carcinoma-in-situ. This work is a first attempt in Italy to evaluate and uniform the criteria adopted for quality control of breast cancer treatment, using a standardised system. Some results are good or excellent, the overall level of compliance with quality indicators is not satisfactory and corrective actions should be undertaken for a number of issues. A continuous monitoring should be performed and appropriate action taken in order to verify the effectiveness of the corrective actions and to provide screen-detected patients with the best quality of care.

Cytotoxic and antiproliferative activity of the CMF regimen administered in association with tamoxifen as primary chemotherapy in breast cancer patients.

Seventy six consecutive patients with T2-4, N0-1, M0 primary breast cancer (BC) received a median of 3 cycles of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) regimen. Tamoxifen was concomitantly administered in patients with estrogen receptor positive (ER+) BC. Ki67 antigen was evaluated immunohistochemically in tumor specimens obtained before chemotherapy and at mastectomy. At post chemotherapy evaluation, tumor shrinkage greater than 50% was obtained in 60 patients (78.9%), 21 of them being complete responders (27.6%). As a whole, primary chemotherapy significantly decreased the number of Ki67 positive cells. More than 50% decrease in Ki67 expression was observed in 78.9% of patients attaining a clinical complete response (CR), in 44.7% of patients with partial remission (PR) and in 50.0% of non-responders, while an increase (>25%) in Ki67 expression was found in 5.3%, 18.4% and 18.7% of patients with CR, PR and non-response, respectively. Both CR and PR rates were superimposable in patients with ER+ and ER- primary BC, while the reduction in Ki67 expression was mainly found in ER+ cases. Patients with increased Ki67 expression from baseline, at the end of primary chemotherapy, had a shorter disease-free interval (70 months) with respect to patients with no change (88+ months) or decrease (87+ months), p<0. 05. To conclude, the activity of CMF + tamoxifen in primary BC does not seem superior to that expected administering CMF alone. The reduction in Ki67 expression, as a whole, correlated with clinical CR, but some individual discrepancies between tumor shrinkage and Ki67 pattern have been observed. The Ki67 reduction mainly confined to the ER+ primary BC suggests that tumor response in this subset may be linked to the reduction in proliferation activity, whereas other mechanisms such as apoptosis might be responsible for the tumor shrinkage in ER- tumors. Since the increase in proliferation activity after primary chemotherapy was associated with a greater recurrence rate and lower disease free interval, irrespective of tumor response, changes in proliferation activity after primary chemotherapy may represent a potentially available parameter that, in addition to the tumor response, can discriminate patients who would benefit from the cytotoxic treatment from patients who would not.

Reopening of persistent left superior caval vein after bidirectional cavopulmonary connections.

Persistent left superior vena cava (SVC) is a not uncommon finding in patients with congenital heart disease. This anatomical variant must be recognised before doing a Glenn anastomosis, bidirectional cavopulmonary connection or a Fontan-type procedure. Following these procedures, reopening of a left SVC leading to clinical cyanosis can occur. Five cases are described in whom persisting left SVCs were excluded before performing a bidirectional cavopulmonary connection or Fontan procedure but (re-)opened after surgery, leading to cyanosis either by reducing effective pulmonary blood flow (bidirectional cavopulmonary connection) or by an obligatory right to left shunt (Fontan). These observations suggest that, embryologically, the lumen of the left SVC obliterates rather than disappears. Balloon occlusion angiography of the innominate vein before cavopulmonary connections or Fontan procedures might improve detection of these collateral vessels.

Results of a mammographic and clinical screening in a health district (USSL) of Brescia, Italy.

AIMS AND BACKGROUND: Screening by mammography has been shown to be effective in reducing breast cancer mortality. We present the results of a mammographic and clinical screening program carried out in an Italian health district. METHODS: The first screening round started in June 1987 and ended in July 1990, and 25,100 women between the age of 50 and 60 years were invited. The second screening round invited 34,332 women between the age of 50 and 64 years and was carried out from September 1990 to September 1993. Women with positive or equivocal results at palpation or mammography were referred for immediate diagnostic assessment followed by surgery, when required. RESULTS: The attendance rate was 67.3% at the first and 62.1% at the repeat screening. At the first screening, 206 biopsies were advised and 197 were performed; 129 of the 197 were found to be malignant. At repeat screening, 248 biopsies were recommended, 208 were performed, and 125 were found to be malignant. The cancer detection rate was 7.7 per thousand at the first and 5.9 per thousand at repeat screening. Of 129 cancers, 107 (83.0%) were T1 at first screening; 6.2% were in situ carcinomas. Axillary lymph nodes were histologically positive in 24% of cases. At repeat screening, 77.6% (97/125) of cancers were T1; 11.2% were in situ carcinomas. Positive axillary lymph nodes were found in 16.8% of cases. CONCLUSIONS: The attendance to screening was satisfactory. A higher frequency of small tumors (83.0%) was found at first screening than before the introduction of screening (56.6%). A marked difference in lymph node positivity (24.0% vs 40.6% in the pre-screening era) was also observed. Such a difference was even more evident at repeat screening. Quality standards of the screening in our study proved to be higher than those currently recommended. The reported results are encouraging, also considering the greater chance for conservative treatment.

Transketolase-TPP-effect in chronic alcoholics with various degrees of liver cirrhosis.

A re-investigation of the use of the transketolase-TPP-effect for the assessment of the thiamine status of chronic alcoholics with various degrees of liver cirrhosis was carried out on 36 alcoholics. The extent of the liver damage in these patients was established by clinical examinations and biochemical tests. Fourteen persons showed no significant hepatic abnormalities, 5 patients had compensated liver cirrhosis, 7 slightly decompensated, and 10 patients suffered from severely decompensated liver cirrhosis. This investigation shows that the transketolase-TPP-effect is also present in patients even with severe liver cirrhosis and that a decrease of the TPP-effect can be observed after oral thiamine administration in these subjects. The TPP-effect of patients with compensated liver cirrhosis was markedly smaller than that of the subjects with slightly or severely decompensated cirrhosis. Accordingly a relationship exists between the TPP-effect and the degree of liver damage. No other correlations however could be established in this respect.

[Diagnostic role of mammography and clinical examination in the framework of a screening program for breast carcinoma in Brescia]. / Ruolo diagnostico della mammografia e dell'esame clinico nell'ambito del programma di screening per il carcinoma mammario a Brescia.

Screening by mammography is at present the only way to obtain good results in terms of diagnosis of breast cancer at an early stage. In this paper we present the results of first and second rounds of a mammographic and clinical screening programme carried out in the health district of Brescia. At the first round out of 129 cancers detected, mammography was diagnostic in 124 cases; in 82 cases, the examination also allowed the identification of a suspicious nodule, while in 42 cases non palpable neoplasm was diagnosed with mammography alone. In the remaining 5 cases mammography was negative and only clinical examination led to the discovery of breast neoplasms. In the second round, in the 125 cancers detected, mammography was diagnostic in 124 cases; clinical examination allowed the identification of 59 of these tumours, while in 65 cases non palpable tumours were found with mammography alone. Only in one case mammography was negative and clinical examination led to the identification of the tumour.

[Merkel cell tumor. Report of case and treatment with octreotide]. / Tumore a cellule di merkel. Segnalazione di un caso e trattamento con octreotide.

Merkel cell carcinoma is a rare neuroendocrine tumor of the skin. Prognosis is very poor particularly when systemic disease is present. Surgery, chemo and/or radiotherapy treatment are not able to guarantee long survival and quality of life is also very poor. We know that neuroendocrine tumor can be in possession of receptors for somatostatin; during the past years, these receptors have been demonstrated in vivo by octreoscan. We report a case of a patient suffering from metastatic Merkel cell carcinoma; because he was elderly, neither chemotherapy nor radiotherapy were possible as a consequence of the explosion of the disease after surgery. The presence of receptors for somatostatin analogues (octreoscan) allowed treatment with octreotide causing the immediate disappearance of metastasis. After ten months of treatment the patient presents a complete remission of disease. Octreotide, the most important somatostatin analogue, represents a primary role in the neuroendocrine tumor management; the drug also lacks of toxicity.

[Octreotide in the treatment of advanced pancreatic tumor. Preliminary study]. / Trattamento con octreotide del carcinoma pancreatico in fase avanzata. Studio preliminare.

BACKGROUND: Data from experimental studies suggest that octreotide, the long acting somatostatin analogue, improves survival of animals with pancreatic cancer. To assess the antitumour effect of octreotide, a randomized trial was performed comparing octreotide with supportive care in advanced pancreatic cancer patients. All patients, aged 59-75 years, were not liable to radical surgical treatment and were not submitted to other treatments (chemo and/or radiotherapy). METHODS: Six patients were enrolled, 4 of these treated with octreotide (500 micrograms two times a day subcutaneous for six months) and the other 2 were inserted a control group. RESULTS: The patients treated with octreotide showed a significant advantage in quality of life (restored appetite, improvement of digestion and intestine function, remission of abdominal pain and preservation of baseline body weight) with a mean > 80 of karnofsky performance score. Monitoring of tumour size changes (US-TC) over the 6 months study period, showed slackened neoplastic growth in all treated patients, whereas neoplasm grew according to an almost exponential trend in untreated patients. Also survival was better in treated patients: in particular, 2 patients out of 4 who completed the study underwent follow-up until they died 12 and 16 months after beginning of treatment, respectively. Karnofsky performance score was particularly high in both patients. This supports the view that octreotide is endowed with antiproliferative activity. CONCLUSION: In conclusion octreotide therapy seems to confer a survival benefit and a better quality of life in advanced pancreatic tumour. Additional studies are needed to confirm these results and to clarify other questions about dose and somatostatin receptors in this kind of tumour.

[Solitary splenic metastasis of bladder carcinoma. Report of a clinical case]. / Metastasi splenica solitaria di carcinoma vescicale. Discussione di un caso clinico.

Several authors assumed that spleen was resistant to neoplastic dissemination because of spleen metastasis are rare in relation to the incidence of metastasis in other parenchymatous organs. We report a clinical case of a symptomatic solitary spleen metastasis in cystic-looking bladder cancer; afterwards we'll examine real incidence of secondary splenic injury. In autopsy studies, the incidence of splenic metastatic spread is in contrast with the rarity of clinical manifestations of solitary metastasis. The case reported is really uncommon: a voluminous single metastasis, cystic-looking, with splenomegaly, abdominal pain and rapid onset. In the presence of a high malignancy primitive tumor, the evaluation of the effective utility of the surgical treatment carried out is premature, because of the relatively short follow-up. On the other hand, the painful symptomatology, the risk of disruption in peritoneal cavity, the impossibility to make inquiries about the nature of the cystic mass, imposed, in our opinion, a surgical treatment.

[Impact of a screening program on the surgical treatment of breast carcinoma]. / Impatto di un programma di screening sul trattamento chirurgico del carcinoma della mammella.

Results are presented concerning the first two cycles of a breast cancer screening program carried out by USSL 41 (the local social health center). 38,000 women were examined in a period ranging from 1987 to 1993 and more than 250 early stage tumors were diagnosed. Early detection by screening is confirmed by tumor size and nodal involvement. Overall, this program carried out in Brescia met requirements set by international and national scientific committees. Good results were obtained as far as quality standards are concerned. The importance of screening is evaluated concerning surgical treatment undergone by the patients. The study of surgical treatment clearly shows the gradual progression of conservative surgery deviating from more destructive operations.

[Tachypnoea and dyspnoea in two infants due to dilated cardiomyopathy associated with an anomalous origin of the left coronary artery]. / Twee tachy- en dyspnoische zuigelingen door gedilateerde cardiomyopathie samenhangend met een afwijkende oorsprong van de linker coronairarterie.

Two infants were referred to the emergency ward: a 3.5-month-old male infant in whom sweating and shortness of breath were seen during drinking and crying, and a 5-week-old girl that had drunk less the past day, moaned while breathing for the past few hours and had become increasingly drowsy. They were not suffering from an infection but from a dilated cardiomyopathy based on an anomalous origin of the left coronary artery from the pulmonary artery. The left coronary artery was then implanted in the aorta surgically. Both patients recovered well. Airway tract infection and sepsis are obvious common differential diagnostic considerations when confronted with a tachy-dyspnoeic infant. However, a cardiac cause, such as a dilated cardiomyopathy with cardiac decompensation, must also be considered as the presentation can be similar. The abnormal origin of the left coronary artery from the pulmonary artery is one of the few readily well treatable causes.

[Conservative surgery in the environment of a screening program for breast carcinoma: evaluation of the results in terms of local recurrence]. / Chirurgia conservativa nell'ambito di un programma di screening per il carcinoma della mammella: valutazione dei risultati in termini di recidiva locale.

This report evaluates the results of conservative surgery plus radiotherapy (QUART) in a group of 123 patients from the screening programme of the District Health Board USSL 41 in Brescia, Italy (over 250 tumours diagnosed in two screening rounds, between 1987 and 1993). To date no recurrence of neoplasms in the operated breast have been diagnosed in either of the two QUART groups (64 patients from the first round, average follow-up 28 months, median 66 months; 59 patients from the second round, average follow-up 28 months, median 30 months). A new carcinoma in the contralateral breast occurred in 3 patients (2 from the first and 1 from the second round), while in 3 cases there was a recurrence in another site (2 from the first and 1 from the second round). These results confirm both the proven effectiveness of conservative treatment in the local control of breast tumours, and the importance of the correct choice of conservative treatment in optimising aesthetic and therapeutic results.