Deficient ferritin immunoreactivity in tissues from niemann-pick type C patients: extension of findings to fetal tissues, H and L ferritin isoforms, but also one case of the rare Niemann-Pick C2 complementation group

Previous studies employing rabbit polyclonal anti-human liver ferritin have shown an absence of L ferritin immunoreactivity in liver and spleen tissue from patients with Niemann-Pick disease type C1 (NPC1). The great majority of NPC cases is caused by defects of the NPC1 gene, and a minority by those of another (NPC2). In this study using polyclonal and monoclonal antibodies we show the deficiency of H and L ferritin isoforms in various NPC tissues, including fetal NPC1, not previously described. In particular, evidence is provided for deficiency in H and L ferritins in tissues, except lung, from a patient with Niemann-Pick disease type C2 (NPC2). The present findings indicate that H and L ferritins are deficient in both NPC types characterized by accumulation of unesterified cholesterol and additional metabolites in the endosomal/lysosomal system. We hypothesize that the lesions in NPC1 and NPC2 block the intracellular utilization not only of cholesterol, but also that of iron for the synthesis of cytosolic ferritin.     

Lobar Lung Transplantation From Deceased Donor: Monocentric Experience

Introduction

Lung transplantation is considered a therapeutic option in selected patients affected by end-stage pulmonary disease. The mortality on the waiting list is mainly attributed to the shortage of the donor pool available for transplantation. There are various strategies to overcome this shortage; one of them is lobar transplantation.

Intraoperative ultrasound score to predict recurrent hepatocellular carcinoma after radical treatments

Despite the high complete necrosis rate of radio-frequency ablation (RFA) or the complete removal following curative hepatic resection (HR), recurrent hepatocellular carcinoma (HCC) remains a significant problem. The aim of the study is to identify some intraoperative ultrasound (IOUS) patterns, predicting intrahepatic recurrences. From January 1997 to July 2009, 410 patients with HCC were treated (162 HR and 248 RFA through a surgical access). All patients were submitted to IOUS examination: 148 IOUS were performed during the laparotomic access while 262 IOUS were performed during the laparoscopic access. Primary HCC was classified according to diameter, HCC pattern (nodular or infiltrative), echogenicity (hyper- or hypo-echoic), echotexture (homogeneous or inhomogeneous), capsular invasion, mosaic pattern, nodule in nodule aspect and infiltration of portal vessels. Number of HCC nodules was also considered. Multivariate analysis (Cox model) was performed to determine features associated with recurrent HCC using IOUS patterns that independently predicted recurrent HCC, a IOUS score was developed. The patients were followed for 3-127 months, (median follow-up: 21.5 months). In 220 patients (54%), intrahepatic recurrences occurred. In 155 patients (38%), distant intrahepatic recurrences arose in different segments at the primary tumor site. In 65 HCC cases (16%), local recurrences were found. At multivariate analysis, multiple nodules, HCC diameter (>20 mm), HCC pattern (infiltrative), hyperechoic nodule and portal infiltration were statistically significant for risk factor of intrahepatic recurrences. Therefore, a IOUS scoring system was calculated on the basis of multivariate analysis and identified three risk categories of patients: in group 1 recurrences occurred in 37%, group 2 in 46% and group 3 in 66% (p = 0.0001). IOUS is an accurate staging tool during “surgical” procedures. This study showed an added value of IOUS: it permitted to identify ultrasound patterns, which can predict the risk of HCC recurrences. The calculated IOUS score permits to intraoperatively evaluate the actual surgical choice and to program the best treatment strategies during the follow-up period. (E-mail: rsantambrogio@mclink.it)     

Control of Tumor Bioenergetics and Survival Stress Signaling by Mitochondrial HSP90s

Tumors successfully adapt to constantly changing intra- and extracellular environments, but the wirings of this process are still largely elusive. Here, we show that heat-shock-protein-90-directed protein folding in mitochondria, but not cytosol, maintains energy production in tumor cells. Interference with this process activates a signaling network that involves phosphorylation of nutrient-sensing AMP-activated kinase, inhibition of rapamycin-sensitive mTOR complex 1, induction of autophagy, and expression of an endoplasmic reticulum unfolded protein response. This signaling network confers a survival and proliferative advantage to genetically disparate tumors, and correlates with worse outcome in lung cancer patients. Therefore, mitochondrial heat shock protein 90s are adaptive regulators of tumor bioenergetics and tractable targets for cancer therapy.     

Factors of delay in the diagnosis of melanoma

Delay in the diagnosis of melanoma was defined as the interval in months from the patient's report of first noticing a suspected lesion to the date of the removal of a histologically confirmed melanoma. 216 patients were included in our study. Total delay was subdivided in three components: patient, medical and referral delay. The major component of delay is due to the patient and the most important cause of it was lack of concern. Lesions in men were detected more frequently by family members, while in women melanomas tended to be self-detected. Nodular melanoma had lower delay but higher thickness. Amelanotic melanomas had a higher delay principally due to the physicians. A significative positive correlation between Breslow thickness and patient delay was observed. The visibility of the tumor and the educational or socio-economic status did not seem to improve early diagnosis. The observation about the shorter delays in thicker tumors lead us to think that educational campaigns should be more focused on recognition of changing or growing lesions than other signs of the ABCD rule and that nodular melanomas are quite different from superficial spreading melanomas.     

Pulmonary lobectomy for lung cancer: a prospective study to compare patients with forced expiratory volume in 1 s more or less than 80% of predicted.

OBJECTIVE: To compare post-operative course, lung function and survival of lung cancer patients with a forced expiratory volume in 1 s (FEV1) more or less than 80% of predicted submitted to lobectomy. METHODS: The data of patients undergoing lobectomy for non small cell carcinoma at the Thoracic Surgery Unit of the Ospedale Maggiore Policlinico of Milan, Italy, were prospectively collected. Inclusion criteria were a radical resectable tumor with size less than 2.5 cm, negative mediastinal nodes, capability to complete pulmonary function tests, Exclusion criteria were FEV1 <40% of predicted, pre- or post-operative chemo or radiotherapy, lobe to be resected receiving more than 30% of the perfusion, incapacity to quit smoking. RESULTS: Eighty-eight patients entered the study and were divided into two groups according to their FEV1%: 45 patients were included in control group (mean FEV1: 92.2%) and 42 in chronic obstructive pulmonary disease group (mean FEV1: 64.2%). Post-operative complications, operative mortality and actuarial survival were the same in the 2 groups. Six months after lobectomy, the mean changes in FEV1 were -14.9% for first group and -3.2% for second group (P<0.001). CONCLUSION: Lobectomy for cancer can be performed successfully also in selected patients with chronic obstructive pulmonary disease. Post-operative course and survival of these patients is not different from that of patients with normal FEV1, on the contrary, patients with low FEV1 may lose less pulmonary function or even mend it.