Reproducibility of the peritoneal regression grading score for assessment of response to therapy in peritoneal metastasis.

The four-tiered peritoneal regression grading score (PRGS) assesses the response to chemotherapy in peritoneal metastasis (PM). The PRGS is used, for example, to assess the response to pressurised intraperitoneal aerosol chemotherapy (PIPAC). However, the reproducibility of the PRGS is currently unknown. We aimed to evaluate the inter- and intraobserver variability of the PRGS. Thirty-three patients who underwent at least three PIPAC treatments as part of the PIPAC-OPC1 or PIPAC-OPC2 clinical trials at Odense University Hospital, Denmark, were included. Prior to each therapy cycle, peritoneal quadrant biopsies were obtained and three haematoxylin and eosin (H&E)-stained step sections were scanned and uploaded to a pseudonymised web library. For determining interobserver variability, eight pathologists assessed the PRGS for each quadrant biopsy, and Krippendorff's alpha and intraclass correlation coefficients (ICCs) were calculated. For determining intraobserver variability, three pathologists repeated their own assessments and Cohen's kappa and ICCs were calculated. A total of 331 peritoneal biopsies were analysed. Interobserver variability for PRGS of each biopsy and for the mean and maximum PRGS per biopsy set was moderate to good/substantial. The intraobserver variability for PRGS of each biopsy and for the mean and maximum PRGS per biopsy set was good to excellent/almost perfect. Our data support the PRGS as a reproducible and useful tool to assess response to intraperitoneal chemotherapy in PM. Future studies should evaluate the prognostic and predictive role of the PRGS

Hypermethioninemia in Campania: Results from 10 years of newborn screening

In the last years tandem mass spectrometry (MS/MS) has become a leading technology used for neonatal screening purposes. Newborn screening by MS/MS on dried blood spot samples (DBS) has one of its items in methionine levels: the knowledge of this parameter allows the identification of infant affected by homocystinuria (cystathionine β-synthase, CBS, deficiency) but can also lead, as side effect, to identify cases of methionine adenosyltransferase (MAT) type I/III deficiency. We started an expanded newborn screening for inborn errors of metabolism in Campania region in 2007. Here we report our ten years experience on expanded newborn screening in identifying patients affected by hypermethioninemia. During this period we screened approximately 77,000 infants and identified two cases: one case of classical homocystinuria and one patient affected by defect of MAT I/III. In this paper we describe these patients and their biochemical follow-up and review the literature concerning worldwide newborn screening reports on incidence of CBS and MAT deficiency

Computed tomography for the evaluation of intrathoracic invasion by lung cancer

We conducted computed tomographic examinations of the chest in 171 patients with lung cancer whose disease was subsequently surgically staged; routine mediastinal exploration was undertaken in all patients undergoing thoracotomy (151), and in 20 patients only anterior mediastinotomy or mediastinoscopy was performed. We have considered three groups of patients: In Group I (including all 171 patients) mediastinal lymph nodes were evaluated for metastatic involvement; nodes were considered diseased when greater than 1 cm. Sensitivity, specificity, and accuracy were 95%, 83%, and 89%. Among these 171 patients, 34 (Group II) had a central tumor otherwise considered operable, which was shown on plain roentgenograms to be in contact with the mediastinum; infiltration of hilar and mediastinal vessels and of mediastinal tissues was investigated preoperatively with computed tomography and then ascertained at thoracotomy. Sensitivity, specificity, and accuracy were 68%, 72% and 70%. Twenty-seven patients (Group III) had a peripheral tumor abutting the pleural surface and suspected to invade the parietal pleura and chest wall; patients with evident bone infiltration were excluded. Sensitivity, specificity, and accuracy of computed tomography were 50%, 90%, and 65%

Maternal VitaminB12 deficiency detected in expanded newborn screening

Introduzione: La disponibilità di nuove tecnologie come la spettrometria di massa tandem ha contribuito enormemente al numero di errori congeniti del metabolismo che possono essere diagnosticati. Infatti, grazie ai programmi di screening metabolico esteso sin dalle prime ore di vita di un neonato, è possibile identificare malattie che possono in tal modo essere trattate precocemente, prima che sintomi clinici, spesso potenzialmente letali, si manifestino. Non esiste però un consenso universale sul pannello più opportuno di patologie da sottoporre a screening (1). Nella Regione Campania si effettua da alcuni anni un progetto pilota di screening neonatale allargato che coinvolge un numero limitato di centri nascita Scopo dello studio e metodi: In questo lavoro abbiamo confrontato l’incidenza, nel periodo 2007-2014, dei disordini metabolici diagnosticati mediante screening metabolico con quella dei disordini individuati nella popolazione dei pazienti per i quali è stato richiesto il dosaggio di aminoacidi e acilcarnitine sulla base di un sospetto clinico. Lo scopo era quello di valutare quanti dei pazienti nati nello stesso periodo in Campania e identificati dopo l’insorgenza dei sintomi clinici avrebbero potuto beneficiare di una diagnosi alla nascita. Risultati e conclusioni: Nel corso della nostra esperienza 26 su 45466 neonati (1:1749) sono stati i casi positivi identificati allo screening neonatale: 5 difetti di acil-CoA deidrogenasi a catena media (MCAD), 3 metilmalonico acidemia (MMA), 7 difetti di vitamina B12 secondari a carenza materna (2), 1 propionico acidemia (PA), 1 isovalerico acidemia, 1 beta-chetotiolasi (βKT), 1 difetto di isobutirril-CoA deidrogenasi, 1 difetto di acil-CoA deidrogenasi a catena corta/ramificata, 1 difetto di 3-metil-crotonil-CoA carbossilasi, 1 difetto di cistationina beta-sintetasi, 2 fenilchetonuria, 1 difetto di carnitina secondario a carenza materna, 1 formiminoglutammico aciduria. Una diagnosi (MCAD) ha consentito l’identificazione della patologia in un fratello asintomatico di 18 mesi che non era stato sottoposto allo screening. Ventisei diagnosi su 2545 (1:98) sono state invece eseguite nel nostro laboratorio su pazienti per i quali il dosaggio degli aminoacidi e delle acilcarnitine in spettrometria di massa tandem era stato richiesto su base clinica. Nell’ambito delle diagnosi post sintomatiche 14/26 sono state effettuate su pazienti nati dopo dell’inizio del progetto di screening metabolico allargato: 5 MMA, 1 PA, 1 βKT, 2 iperglicinemia non chetotica, 1 encefalopatia etilmalonica, 1 difetto di metilene-tetraidrofolato reduttasi, 2 difetti di 3-idrossi-acil-CoA deidrogenasi a catena lunga, 1 difetto di proteina trifunzionale mitocondriale. In conclusione, i dati ottenuti sottolineano la numerosità delle diagnosi effettuate in mancanza di screening, quando ormai il difetto metabolico si è tradotto in un danno d’organo, in uno stadio in cui il potenziale effetto della terapia è compromesso e ribadiscono l’importanza dello screening neonatale quale unico protocollo per la tempestiva diagnosi di malattie del metabolismo. 1- Watson MS. et al, Pediatrics 2006; 117: S296-307. 2- Scolamiero E. et al, Clin Biochem. 2014 doi: 10.1016/j.clinbiochem.2014.08.020 [Epub ahead of print

Computed tomography for the evaluation of intrathoracic invasion by lung cancer

We conducted computed tomographic examinations of the chest in 171 patients with lung cancer whose disease was subsequently surgically staged; routine mediastinal exploration was undertaken in all patients undergoing thoracotomy (151), and in 20 patients only anterior mediastinotomy or mediastinoscopy was performed. We have considered three groups of patients: In Group I (including all 171 patients) mediastinal lymph nodes were evaluated for metastatic involvement; nodes were considered diseased when greater than 1 cm. Sensitivity, specificity, and accuracy were 95%, 83%, and 89%. Among these 171 patients, 34 (Group II) had a central tumor otherwise considered operable, which was shown on plain roentgenograms to be in contact with the mediastinum; infiltration of hilar and mediastinal vessels and of mediastinal tissues was investigated preoperatively with computed tomography and then ascertained at thoracotomy. Sensitivity, specificity, and accuracy were 68%, 72% and 70%. Twenty-seven patients (Group III) had a peripheral tumor abutting the pleural surface and suspected to invade the parietal pleura and chest wall; patients with evident bone infiltration were excluded. Sensitivity, specificity, and accuracy of computed tomography were 50%, 90%, and 65%