Review article: liver transplantation for HCC. Treatment options on the waiting list

The most widely adopted criteria to admit and maintain patients with HCC and cirrhosis in the waiting list for liver transplantation are the Milano criteria, consisting in the presence of a single tumour ≤ 5 cm in diameter or up to three tumours, none exceeding 3 cm in diameter. Since the average time to transplantation has become longer than 10-12 months in most European and American Centers, the exclusion from the list during the waiting period due to increase of the neoplasm over the established criteria is not uncommon at present. It is mandatory, therefore, to seek an effective therapeutic strategy for patients with HCC waiting for transplantation. Surgical resection and eventual subsequent salvage transplantation seems a cost-effective strategy in resectable HCC. In unresectable neoplasms both transarterial chemoembolization and percutaneous ablation techniques are currently used and one or the other are chosen according to individual applicability, limitations and specific risks. However, although positive trends were reported, no definitive evidence has been produced so far about their efficacy in increasing patient's survival and decreasing tumour recurrence rates after transplantation. Adult-to-adult living donor liver transplantation is one possible way to shorten the waiting list, but this strategy involves important ethical implications. At present it appears justified to take it into consideration only if the waiting time for cadaveric OLT is expected to exceed 7 months. A more general and definitive attempt to overcome problems related to long waiting times for patients with HCC and relatively preserved hepatic function has been introduced in the USA very recently and consists in prioritizing patients with HCC. However, the overall efficacy of this approach will be established only in some years

Epidemiology and drug susceptibility of nontuberculous mycobacteria (NTM) in Italy in 2016-2020

Introduction. Nontuberculous mycobacteria (NTM) are environmental mycobacteria which may cause pulmonary and extrapulmonary diseases. These organisms are difficult to treat due to their intrinsic drug-resistance. In Italy, no major nationwide study on NTM epidemiology and drug susceptibility was performed. Methods. Data on the epidemiology of 7,469 NTM clinical isolates identified in Italy in 2016-2020 and on the minimum inhibitory concentrations (MICs) of 1,506 of these strains were analysed. Results. Overall, 63 species were identified in 42 hospital laboratories located in 16 out of 20 regions, with Mycobacterium avium complex (MAC) being the most frequently iso-lated, followed by M. gordonae, M. xenopi, M. abscessus. The MICs of 12 drugs for MAC, M. xenopi, M. kansasii, M. abscessus, M. fortuitum and M. chelonae were interpreted for clinical significance (susceptible, intermediate, resistant) based on the guidelines pub-lished by the Clinical and Laboratory Standards Institute in November 2018. Conclusions. Our data are in line with other nationwide studies and may be of value for further update of microbiological and clinical guidelines

Unusual presentation of melanoma liver metastases superimposed to multiple Focal Nodular Hyperplasia nodules

Clinical History: Unusual case of well known multiple focal nodular hyperplasia (FNH) foci colonized by haematogenous spread of melanoma metastases in a young woman previously operated for cutaneous melanoma. Morphological change of FNH appearance at Spiral CT and pathogenesis of "hidden" metastatic melanoma lesions, almost exclusively located within multiple FNH, are described

A comparative study on Capecitabine (Cape) pharmacokinetics (PK) in elderly or younger patients with metastatic breast (MBC) or colo-rectal cancer (CRC)

Background: Cape is an efficient oral prodrug of 5FU in MBC and CRC. Unexpected severe toxicity in older patients (pts) was reported after standard dose of 2500mg/sm/day. About 70% of drug and metabolites are excreted with the urine and a 25% reduction of the dose is recommended if the pt has a creatinine clearance (CrCl) <50ml/min. However no prospective study has been done on Cape PK in the elderly pts. Methods: Between Oct 2004 and Nov 2005, 21 pts with MBC or CRC and age >70yrs or <60yrs who received Cape (1000 mg/sm bid for 14 days every 21 days) entered the study after giving signed informed consent. CrCl was calculated according to the Cockcroft-Gault method. Patient characteristics: 15 elderly pts (median 78 range71-84yrs), 6 younger pts (median 50.5 range 43-57yrs); 9 (42.9%) males and 12 (57.1%) females; median KPS 90 (range 70-100); 8 MBC pts (38%), 13 CRC pts (62%). Blood samples were taken on the first day of treatment at time 0 and at 0.25,0.5,1,2,3,4,5,6,8 hrs after the first drug administration and on 4th, 8th, 12th and 14th days in the morning. Plasma levels of Cape, 5DFUR, 5DFCR and 5FU were determined by a validated HPLC method and UV detection. Results: At present PK data after the first administration of Cape are available for 13 pts (9 elderly; 4 younger). The mean Cape and 5DFCR AUC0-8hr are higher in older patients (Cape 6653±2564.8 vs. 4427±2714.5; P=0.09; 5DFCR 8635±5197.1 vs. 6292±3813.6; P=0.26), while no evident differences are present for 5DFUR and 5FU. The same results are obtained both in pts with CrCl 50 ml/min. The ratios of DFUR_AUC to Cape_AUC and 5FU_AUC to Cape_AUC are conversely higher in younger than in older pts (mean: 2.2 vs 1.62). A large interindividual variability in the concentration/time curves is present for Cape and metabolites. Cape dose reduction because of G3 toxicity (2 hand-foot syndrome, 1 stomatitis) was performed in 3 elderly pts. Drug systemic exposure was higher in 2 of these pts independently of CrCl. Conclusions: The preliminary results of this PK study suggest that elderly patients treated with Cape at 1000 mg/sm/bid are more drug-exposed than younger patients, independently of renal function. PK analysis is ongoing for the remaining patients