A meta-analysis on the influence of partial biopsy of primary melanoma on disease recurrence and patient survival.

BACKGROUND: Complete surgical excision is the preferred biopsy type for suspicious melanocytic lesions. However, partial biopsy is sometimes used in special situations. Previous studies have explored the effect of partial biopsy of a primary melanoma on patient outcome with controversial results. OBJECTIVE: We performed a meta-analysis on the influence of the type of biopsy of a primary melanoma on recurrence-free survival (RFS) and melanoma-related survival (MRS). METHODS: Clinical trials, observational cohort studies and case-control studies reporting absolute number of recurrences and/or melanoma-related deaths in patients undergoing a partial or excisional biopsy of melanoma were included in the meta-analysis. RESULTS: In all, the five included studies reported 3249 patients, 1121 (34.5%) of them in the partial biopsy group and 2128 (65.5%) in the excisional biopsy group. Despite a trend in favour of excisional biopsy in reducing the risk for recurrences, the forest plot related to RFS failed to demonstrate significant differences among groups (RR: 1.27; 95% CI 0.97-1.67; P: 0.09; random effects; I2 : 55%). The forest plot showed no difference in the risk of dying for melanoma-related causes for patients undergoing partial biopsy vs. excisions biopsy (RR: 1.50; 95% CI 0.98-2.30; P: 0.06; random effects; I2 : 60%). LIMITATIONS: The majority of the studies were retrospective, and follow-up time was not uniform among studies and not always reported. CONCLUSION: In conclusion, a partial biopsy can be performed in special situations, such as large primary tumours located in surgically sensitive areas, without altering MRS and RFS.

A New SERPINA-1 Missense Mutation Associated with Alpha-1 Antitrypsin Deficiency and Bronchiectasis.

Alpha-1-antitrypsin deficiency (AATD) is a genetic condition caused by SERPINA1 mutations, which culminates into lower protease inhibitor activity in the serum and predisposes to emphysema. Clinical manifestations of AATD are often associated to ZZ (p.Glu342Lys) and SZ (p.Glu264Val) genotypes and less frequently to rare deficiency or null alleles in heterozygous and homozygous states. We report a case of a 52-year-old woman with bronchiectasis without other potential causes other than an electrophoresis that showed a decrease of alpha-1 globin band and AAT levels below the normal value (78 mg/dl; v.n. 90-200 mg/dl). No S or Z mutation was identified, but sequencing analysis found a novel missense variant Ile74Asn (c.221T > A) in heterozygous state on an M3 allele (Glu400Asp) in the exon 2 of the SERPINA-1gene, probably leading to a dysfunctional protein. This mutation has never been previously identified, and it is interesting to note the association with bronchiectasis in the absence of emphysema.

Analysis of mitochondrial DNA alteration in new phenotype ACOS.

BACKGROUND: Mitochondria contain their own DNA (MtDNA) that is very sensitive to oxidative stress and as a consequence could be damaged in quantity. Oxidative stress is largely recognized to play a key role in the pathogenesis of asthma and COPD and might have a role in the new intermediate phenotype ACOS (asthma-COPD overlap syndrome). The aim of this study was to investigate MtDNA alterations, as an expression of mitochondrial dysfunction, in ACOS and to verify whether they might help in the identification of this new phenotype and in its differentiation from asthma and COPD. METHODS: Ten (10) ACOS according to Spanish guidelines, 13 ACOS according to GINA guidelines, 13 COPD, 14 asthmatic patients and ten normal subjects were enrolled. They further underwent a blood, induced sputum and exhaled nitric oxide collection. Content of MtDNA and nuclear DNA (nDNA) were measured in the blood cells of patients by Real Time PCR. RESULTS: ACOS patients showed an increase of MtDNA/nDNA ratio. Dividing ACOS according to guidelines, those from the Spanish showed a higher value of MtDNA/nDNA compared to those from GINA/GOLD (92.69 ± 7.31 vs 80.68 ± 4.16). Spanish ACOS presented MtDNA/nDNA ratio closer to COPD than asthma. MtDNA was higher in asthmatic, COPD, GINA and Spanish ACOS patients compared to healthy subjects (73.30 ± 4.47-137.0 ± 19.45-80.68 ± 4.16-92.69 ± 7.31 vs 65.97 ± 20.56). CONCLUSION: We found an increase of MtDNA/nDNA ratio in ACOS subjects that led us to conclude that there is presence of mitochondrial dysfunction in this disease, that makes it closer to COPD than to asthma. Although the MtDNA/nDNA ratio results are a useful marker for differential diagnosis from asthma, COPD and ACOS, further studies are needed to confirm the potentiality of MtDNA/nDNA ratio and to a better characterization of ACOS.

Whole-body MR-DWIBS vs. [18F]-FDG-PET/CT in the study of malignant tumors: a retrospective study.

PURPOSE: Our aim was to assess the overall diagnostic accuracy of magnetic resonance diffusion-weighted whole-body imaging with background signal suppression (MR-DWIBS) compared with ([(18)F]-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT), considered the reference standard of whole-body tumour imaging modalities, in a series of consecutive patients with malignant tumour. MATERIALS AND METHODS: Thirty-eight patients diagnosed with a malignant tumour over a 4-month period were enrolled in this retrospective, observational study. PET/CT and MR-DWIBS images were reviewed in double-blind manner by a nuclear medicine physician and radiologists with 4 years experience. Lesion size, standard uptake value (SUV) and apparent diffusion coefficient (ADC) were measured and calculated for each lesion. RESULTS: The qualitative analysis of MR-DWIBS and [(18)F]-FDG-PET/CT showed that two patients were negative at both techniques. MR-DWIBS was positive in 36 patients, 34 of whom were positive and two negative at [(18)F]-FDG-PET/CT, respectively. Two hundred and fifty-five lesions were identified by MR-DWIBS and 184 by [(18)F]-FDG-PET/CT, which was a significative discordance. Correlation between SUV and ADC of lesions positive at both techniques was not statistically significant. The mean difference between lesion size in [(18)F]-FDG-PET/CT and MR-DWIBS was not statistically significant. No correlation was found between glucose metabolism and water motion. CONCLUSIONS: MR-DWIBS may be used to evaluate localisation of parenchymal neoplasms but is less efficacious in characterising lymph-node and skeletal lesions. [(18)F]-FDG-PET/CT remains the best whole-body technique to identify lymph-node and skeletal lesions, but its limitation is identifying tumours with low glucose metabolism as in mucinous neoplasms. MR-DWIBS evaluation must be integrated with morphological images to increase MR diagnostic accuracy.

Study of mitochondrial DNA alteration in the exhaled breath condensate of patients affected by obstructive lung diseases.

Mitochondrial DNA (MtDNA) has been studied as an expression of oxidative stress in asthma, COPD, lung cancer and obstructive sleep apnea, but it has been mainly investigated systemically, although the pathogenetic mechanisms begin in the airways and only later progress to systemic circulation. The aim of this study was to investigate the MtDNA alterations in the exhaled breath condensate (EBC) of patients with asthma, COPD and asthma-COPD overlap syndrome (ACOS). In order to analyze better what happens to mitochondria, both locally and systemically, we compared MtDNA/nDNA in blood and EBC of paired patients. Thirteen (13) COPD patients, 14 asthmatics, 23 ACOS (10 according to Spanish guidelines, 13 in line with GINA guidelines) and 12 healthy subjects were enrolled. Patients underwent clinical and functional diagnostic tests as foreseen by the guidelines. They underwent blood and EBC collection. Content of MtDNA and nuclear DNA (nDNA) was measured in the blood cells and EBC of patients by Real Time PCR. The ratio between MtDNA/nDNA was calculated. For the first time we were able to detect MtDNA/nDNA in the EBC. We found higher exhaled MtDNA/nDNA in COPD, asthmatic and ACOS patients respectively compared to healthy subjects (21.9 ± 4.9 versus 6.51 ± 0.21, p < 0.05; 7.9 ± 2.5 versus 6.51 ± 0.21, p = 0.06; 18.3 ± 3.4 versus 6.51 ± 0.21, p < 0.05). The level of exhaled MtDNA/nDNA was positively correlated with the plasmatic one. The levels of MtDNA/nDNA in the EBC, as expression of oxidative stress, are increased in COPD, asthmatic and ACOS patients compared to healthy subjects. These are preliminary results in a small number of well characterized patients that requires confirmation on a larger population. We support new studies directed toward the analysis of exhaled MtDNA/nDNA as a new exhaled non-invasive marker in other inflammatory/oxidative airways diseases.