Health-related quality of life trajectories in melanoma patients after electrochemotherapy: real-world insights from the InspECT register.

BACKGROUND: Electrochemotherapy (ECT) effectively controls skin metastases from cutaneous melanoma. OBJECTIVES: This study aimed to evaluate health-related quality of life (HRQoL) in melanoma patients pre-/post-ECT and its effect on treatment outcome. METHODS: The analysis included prospective data from the International Network for Sharing Practices of ECT register. Following the Standard Operating Procedures, patients received intravenous or intratumoural bleomycin (15,000 IU/m2 ; 1000 IU mL/cm3 ) followed by 100-microsecond, 1000-V/cm electric pulses. Endpoints included response (RECIST v3.0), local progression-free survival (LPFS), toxicity (CTCAE v5.0), and patient-reported HRQoL at baseline, one, two, four and ten months (EuroQol [EQ-5D-3L], including 5-item utility score [EQ-5D] and visual analogue scale for self-reported health state [EQ-VAS]). Comparisons within/between subgroups were made for statistical and minimal important differences (MID). HRQoL scores and clinical covariates were analysed to identify predictors of response in multivariate analysis. RESULTS: Median tumour size was 2 cm. Complete response rate, G3 toxicity and one-year LPFS in 378 patients (76% of the melanoma cohort) were 47%, 5%, and 78%. At baseline, age-paired HRQoL did not differ from the general European population. Following ECT, both EQ-5D and EQ-VAS scores remained within MID boundaries, particularly among complete responders. A subanalysis of the EQ-5D items revealed a statistically significant deterioration in pain/discomfort and mobility (restored within four months), and self-care and usual activities (throughout the follow-up) domains. Concomitant checkpoint inhibition correlated with better EQ-5D and EQ-VAS trajectories. Baseline EQ-5D was the exclusive independent predictor for complete response (RR 14.76, p=0.001). CONCLUSIONS: HRQoL of ECT melanoma patients parallels the general population and is preserved in complete responders. Transient deterioration in pain/discomfort and mobility and persistent decline in self-care and usual activities may warrant targeted support interventions. Combination with checkpoint inhibitors is associated with better QoL outcomes. Baseline HRQoL provides predictive information which can help identify patients most likely to respond.

Evaluation of health status in patients with hepatitis c treated with and without interferon.

BACKGROUND: The evolution of technology in healthcare has increased the health care's costs and, the universal healthcare systems, in developed countries, need to ensure proper allocation of resources. Thus, the major issue is assessing the effectiveness of new medical technologies. The evaluation of quality of life in response to new treatments has become a key indicator in chronic conditions for which medical interventions are evaluated not only in terms of increasing the number of expected life years but also in terms of increasing quality of life. The aim of this observational study was to verify whether a simple instrument (EQ-5D-5 L) can capture variations in health-related quality of life (HRQoL) and allow us to evaluate the impact of different drug treatment protocols in patients with hepatitis C virus (HCV) on daily activities. METHODS: Sixty six patients with HCV were consecutively enrolled in the Hepatology Unit at the University Hospital of Catania "G. Rodolico". Sixteen patients received new direct-acting-antiviral agents (DAAs) plus pegylated alpha interferon (Peg-α-IFN) protocol (Group A) and 50 DAAs IFN free protocol (Group B). The EQ-5D-5 L® questionnaire and visual analog scale (VAS) were given to both groups to calculate coefficient's utility. We used the EQ-5D-5 L Crosswalk Index Value Calculator to obtain the utility EQIndex and both parametric and non parametric tests for the statistical analysis. RESULTS: The biopsy taken at the beginning of treatment showed comparable cell damage in both groups. The difference in the VAS results was negative for patients who received protocols containing IFN (indicating decreased quality of life),whereas it was positive in patients treated with IFN-free protocols. The baseline EQIndex did not reveal any differences between the two treatment groups. The post-treatment EQIndex was statistically better in the groups that received IFN-free therapy. CONCLUSIONS: When innovative treatments are introduced into clinical practice, assessing quality of life is mandatory to determine their benefits. The instruments used in the present study are effective in detecting the areas in which improvement has occurred. These instruments can be easily managed by general practitioners for follow up of progression of the disease and referred to the specialist.

Electrochemotherapy in the treatment of metastatic malignant melanoma: a prospective cohort study by InspECT.

BACKGROUND: (ECT) is an effective local treatment for cutaneous metastasis. Treatment involves the administration of chemotherapeutic drugs followed by delivery of electrical pulses to the tumour. OBJECTIVES: To investigate the effectiveness of ECT in cutaneous metastases of melanoma and to identify factors that affect (beneficially or adversely) the outcome. METHODS: Thirteen cancer centres in the International Network for Sharing Practices on Electrochemotherapy consecutively and prospectively uploaded data to a common database. ECT consisted of intratumoral or intravenous injection of bleomycin, followed by application of electric pulses under local or general anaesthesia. RESULTS: In total, 151 patients with metastatic melanoma were identified from the database, 114 of whom had follow-up data of 60 days or more. Eighty-four of these patients (74%) experienced an overall response (OR = complete response + partial response). Overall, 394 lesions were treated, of which 306 (78%) showed OR, with 229 showing complete response (58%). In multivariate analysis, factors positively associated with overall response were coverage of deep margins, absence of visceral metastases, presence of lymphoedema and treatment of nonirradiated areas. Factors significantly associated with complete response to ECT treatment were coverage of deep margins, previous irradiation of the treated area and tumour size (< 3 cm). One-year overall survival in this cohort of patients was 67% (95% confidence interval 57-77%), while melanoma-specific survival was 74% (95% confidence interval 64-84%). No serious adverse events were reported, and the treatment was in general very well tolerated. CONCLUSIONS: ECT is a highly effective local treatment for melanoma metastases in the skin, with no severe adverse effects noted in this study. In the presence of certain clinical factors, ECT may be considered for local tumour control as an alternative to established local treatments, or as an adjunct to systemic treatments.

Combined duodenal and pancreatic major trauma in high risk patients: can a partial reconstruction be safe?

Pancreatic trauma is an uncommon injury, occurring in only about 0.2% of blunt abdominal injuries, while duodenal injuries represent approximately 4% of all blunt abdominal injuries. When trauma of the pancreas and duodenum do not permit reparation, pancreatoduodenectomy (PD) is mandatory. In the reconstructive phase, the use of ductal ligation as an alternative to standard pancreaticojejunostomy has been reported by some authors. We report a case of polytrauma with pancreatic and duodenal injury in which the initial diagnosis failed to recognize the catastrophic duodenal and pancreatic situation. The patient was submitted for PD and the pancreatic stump was abandoned in the abdominal cavity after main pancreatic ductal ligation. This technique can minimize the morbidity and mortality of PD in patients with other organs or apparatus involved severely and extensively in trauma.

Diagnostic and prognostic value of alpha-fetoprotein, des-γ-carboxy prothrombin and squamous cell carcinoma antigen immunoglobulin M complexes in hepatocellular carcinoma.

The hepatocellular carcinoma (HCC) is one of the most common malignant tumors. It carries a poor survival rate and has an increasing incidence worldwide. In most cases, HCC is diagnosed at a late stage. Therefore, the prognosis of patients with HCC is generally poor and has a less than 5% 5-year survival rate. The aim of this study was compare the accuracy of α-fetoprotein (AFP), des-γ- carboxy prothrombin (DCP), squamous cell carcinoma antigen-immunoglobulin M complexes (SCCA-IgM Cs) in the early diagnosis and in the prognosis of HCC. A literature search identified the markers for hepatocellular carcinoma. A search of the literature was made using cancer literature and the PubMed database for the following keywords: "markers and HCC", "α-fetoprotein (AFP) and HCC", "Des-γ-carboxy prothrombin"(DCP) and HCC, "squamous cell carcinoma antigen-immunoglobulin M complexes" (SCCA-IgM Cs). Despite the large number of studies devoted to the immunohistochemistry of HCC, at the present time, the absolute positive and negative markers for HCC are still lacking, and even those characterized by very high sensitivity and specificity do not have an universal diagnostic usefulness. In conclusion none of the three biomarkers (AFP, DCP, SCCA-IgM Cs) is optimal. According to recent reviews, these biomarkers should be measured simultaneously and in combination with imaging techniques to increase the sensitivity, specificity, diagnostic accuracy and to make a reliable prognosis. Currently the recommended screening strategy for patients with cirrhosis includes the determination of serum AFP levels and an abdominal ultrasound every six months to detect HCC at an earlier stage.

Carotid intima-media thickness and liver histology in hemodialysis patients with nonalcoholic Fatty liver disease.

The prevalence of atherosclerotic cardiovascular disease in chronic hemodialysis (HD) patients has been demonstrated to be higher than in healthy people. Severe liver fibrosis is strongly associated with early carotid atherosclerosis and it might reduce the survival of patients who undergo both renal replacement therapy and transplantation. We wanted to assess whether nonalcoholic fatty liver disease (NAFLD) was associated with altered intima-media thickness (IMT) in HD patients as an independent marker of subclinical atherosclerosis. We enrolled 42 patients undergoing HD and 48 patients with normal renal function, all of them with high levels of aminotransferases and an ultrasonographic diagnosis of liver steatosis. The control group consisted of 60 healthy subjects. Laboratory tests for inflammatory and oxidative markers, ultrasonographic liver evaluation, carotid IMT measurement, and liver biopsy were performed. Different degrees of fibrosis were detected in our study cohort. Worse liver histopathological scores and higher plasmatic levels of C-reactive protein, reactive oxygen species, and vascular cell adhesion molecule-1 were found in HD patients. Carotid IMT was significantly higher (p < 0.005) in patients with histological steatosis. HD patients may develop active and progressive chronic hepatitis faster than patients with normal renal function and the thickness of their carotid intima-media might be markedly increased. These two conditions seem to be independent on classical risk factors and on metabolic syndrome. They might be related to the high levels of oxidants and to the inflammatory state, which are typical of patients undergoing HD. Independently related with the traditional risk factors for cardiovascular disease, nonspecific inflammation and oxide-reductive imbalance may play an important role in the progression of NAFLD and atherosclerotic disease in HD patients.

Electrochemotherapy in the treatment of cutaneous malignancy: Outcomes and subgroup analysis from the cumulative results from the pan-European International Network for Sharing Practice in Electrochemotherapy database for 2482 lesions in 987 patients (2008-2019).

BACKGROUND: Electrochemotherapy (ECT) is a treatment for both primary and secondary cutaneous tumours. The international Network for sharing practices on ECT group investigates treatment outcomes after ECT using a common database with defined parameters. METHODS: Twenty-eight centres across Europe prospectively uploaded data over an 11-year period. Response rates were investigated in relation to primary diagnosis, tumour size, choice of electrode type, route of bleomycin administration, electrical parameters recorded and previous irradiation in the treated field. RESULTS: Nine hundred eighty-seven patients, with 2482 tumour lesions were included in analysis. The overall response (OR) rate was 85% (complete response [CR]: 70%, partial response rate: 15%, stable disease: 11%, and progressive disease: 2%). For different histologies, OR and CR rates for metastases of malignant melanoma were 82% and 64%, basal cell carcinoma were 96% and 85%, breast cancer metastases were 77% and 62%, squamous cell carcinoma were 80% and 63% as well as Kaposi's sarcoma were 98% and 91%, respectively. Variance was demonstrated across histotypes (p < 0.0001) and in accordance with size of lesion treated (dichotomised at diameter of 3 cm (p < 0.0001). Hexagonal electrodes were generally used for larger tumours, but for tumours up to 3 cm, linear array electrodes provided better tumour control than hexagonal electrodes (80%:74%, p < 0.003). For tumours more than 2 cm, intravenous administration was superior to intratumoural (IT) administration (p < 0.05). Current recorded varied across tumour histologies and size but did not influence response rate. In previously irradiated areas, responses were selectively lower for IT administration. CONCLUSIONS: These cumulative data endorse efficiency of ECT across a broad range of histotypes. Analysis of 2482 lesions details subgroup analysis on treatment response informing future treatment choices.

Altered pattern of circulating matrix metalloproteinases -2,- 9 and tissue inhibitor of metalloproteinase-2 in patients with HCV-related chronic hepatitis. Relationship to histological features.

AIM: The aim of this paper was to assess circulating levels of metalloprotease2 (MMP2), metalloprotease9 (MMP9) and tissue inhibitor of metalloprotease2 (TIMP2) in patients with HCV-related chronic hepatitis to verify whether there was a relationship between these molecules and biochemical and histological features. METHODS: Forty-nine neodiagnosed and untreated patients affected by chronic C hepatitis and twenty healthy control subjects were investigated. In overall study series, circulating levels of MMP2, MMP9 and TIMP2 were assessed by ELISA commercial kit (R&D Systems). Patients with chronic hepatitis undergone to liver biopsy and histological features were examined according to Histological Activity Index (HAI). RESULTS: Mean values of MMP2 (1989+/-207 ng/mL. vs 1112+/-120 ng/mL), MMP9 (62.44+/-11.9 ng/mL vs 39.67+/-4.6 ng/mL) and TIMP2 (48.3+/-8.1 ng/mL vs 15.16+/-4.1 ng/mL) were significantly higher (P<0.001) in patients than in controls. Among investigated molecules, only MMP2 was independently related to inflammation and fibrosis according to grading (P=0.036) and staging (P=0.032) score. Moreover, MMP2 but not MMP9 and TIMP2 was related to AST (P=0.015), ALT (P=0.049) and AST/platelet ratio index (P=0.001). No relationship (P>0.05) was found between MMP2 and MMP9 or TIMP2. CONCLUSIONS: Our study confirms an altered pattern of metalloproteases and their tissue inhibitors in subjects with chronic C hepatitis and such alterations can contribute to development of liver fibrosis. In addition MMP2 is related to inflammation and fibrosis as assessed by liver biopsy and laboratory features. The serial detection of MMP2 could help to monitor evolution of disease and to predict onset of cirrhosis.

A study about mechanisms of des-gamma-carboxy prothrombin's production in hepatocellular carcinoma.

AIM: Des-gamma-carboxy prothrombin (DCP) is an abnormal prothrombin, increased in serum of patients with hepatocellular carcinoma (HCC) as result of an acquired defect of post-translational carboxylation of prothrombin's precursor. It is unclear if the reduced activity of gamma-carboxylase is secondary to vitamin K deficiency or to an altered gene encoding this enzyme. The aim of this study was to evaluate the effect of vitamin K administration on DCP and alpha-fetoprotein (AFP) levels, to identify a relationship between vitamin K and DCP serum levels and to investigate mechanisms of serum elevation of DCP levels. METHODS: The authors determined DCP and AFP serum levels and vitamin K concentration in 64 cirrhotics with HCC and in 60 cirrhotic subjects without HCC. In HCC subjects DCP and AFP levels were measured before and after vitamin K administration. A t-test for unpaired data was applied (P values <0.05 statistically significant). RESULTS: Only HCC patients had detectable levels of DCP and significant AFP levels. Administration of vitamin K reduced DCP but not AFP levels in HCC patients. No correlation was observed between vitamin K concentration and DCP levels: vitamin K concentration was similar both in HCC patients and in control group without HCC; HCC patients had the same vitamin K concentration regardless of elevated o reduced DCP levels after vitamin K administration. CONCLUSION: DCP detectable serum levels are the result not only of vitamin K deficiency or selective defects of carboxylase, because probably alterations of membrane receptors or cytoplasmatic transfers, that are necessary for the function of vitamin K, are involved.

Plasma ICAM-1 and VCAM-1 levels in type 2 diabetic patients with and without microalbuminuria.

AIM: Aim of the study was to investigate plasma levels of intercellular adhesion molecule-1 (s-ICAM-1) and vascular cellular adhesion molecule-1 (s-VCAM-1) in a cohort of type 2 diabetic patients, compared to healthy control subjects, to verify whether there are differences between these two molecules and to evaluate a possible correlation with the presence of microangiopathy. METHODS: Plasma ICAM-1 and VCAM-1 levels in 49 type 2 diabetic patients, 28 microalbuminuria patients and 21 normoalbuminuria patients were investigated and compared to same levels of 15 healthy control subjects. ICAM-1 and VCAM-1 were assayed by EIA commercial kit (R&D System Co, Abington, UK), according to procedures described by the manufacturer and concentrations expressed as ng/mL. Mean +/- standard deviation (SD) values for each group were compared by t test for unpaired data and Kruskall-Wallis test. Statistical significance was set at P<0.05. RESULTS: Mean +/- SD plasma ICAM-1 was 12.96 +/- 1.08 ng/mL in controls, 18.56 +/- 2.3 ng/mL in normoalbuminuria patients and 26.25 +/- 4.1 ng/mL in microalbuminuria patients, respectively. Mean +/- SD plasma VCAM-1 was 15.96 +/- 4.02 ng/mL in controls, 17.13 +/- 7.5 ng/mL in normoalbuminuria patients and 26.84 +/- 5.99 ng/mL in microalbuminuria patients, respectively. Statistical analysis showed a significant difference in ICAM-1 levels between controls and normoalbuminuria patients (P<0.05) and between these and microalbuminuria patients (P<0.05). VCAM-1 levels were significantly higher in microalbuminuria than in normoalbuminuria patients (P<0.05), but no significant difference was found between normoalbuminuria patients and control subjects (P>0.05). CONCLUSION: Reported results show that circulating ICAM-1 is higher in microalbuminuria than in normoalbuminuria patients and also in normoalbuminuria patients than in control subjects. Circulating VCAM-1 has increased only in microalbuminuria patients. Therefore, these two molecules have different ability to assess temporal relationship between inflammatory activity and microvascular complications.

The supraclavicular artery island flap (SCAIF) in head and neck reconstruction: an Italian multi-institutional experience.

The supraclavicular artery island flap (SCAIF) is a thin and pliable pedicled flap that is easy and quick to harvest. Thanks to its particular features and high reliability, it is best indicated for the elderly or most fragile patients. SCAIF is very versatile, as it can be used for reconstruction of oral cavity, oropharynx, hypopharynx, facial and cervical skin and tracheostomal defects. We began using this flap in four Italian tertiary referral centres, with several indications, both as first treatment and as salvage surgery. The aim of the study was to demonstrate the easy reproducibility of the flap among four different centres. A series of 28 patients underwent head and neck reconstructions with SCAIF with no recorded complications during flap harvesting. After the very first cases, harvesting time was approximately 45 minutes; 24 patients had successful flap integration at the recipient site, while the remaining 4 suffered from partial flap necrosis, two of whom needed revision surgery. Other minor complications were reported at the recipient site, always at the most distal and most delicate portion of the flap. Donor site was always closed primarily, with only three cases of partial suture dehiscence. We only selected the most fragile patients for SCAIF reconstruction, such as the elderly or those with one or more comorbidities; for this reason, we reported some serious systemic complications and one intraoperative death. SCAIF is an easy reproducible flap, with multiple possible indications. Its use as an alternative to free flaps in the head and neck region is nowadays under discussion. Its use should be encouraged among head and neck surgeons thanks to its various advantages.

Meaning of elevated CA 19-9 serum levels in chronic hepatitis and HCV-related cirrhosis.

AIM: Carbohydrate 19-9 antigen (CA 19-9) has been used in the diagnosis and follow-up of gastrointestinal tumors. However, a remarkable reduction of specificity has been described in subjects with chronic diseases. Elevated CA 19-9 serum levels have been described in non neoplastic liver diseases, such as hepatic cirrhosis, where they correlate with the fibrosis grade and the disease severity. The aim of the study is to evaluate CA 19-9 levels in chronic hepatitis patients (CH) and hepatic cirrhosis patients, Hepatitis C Virus (HCV)-correlated. Our goal was to establish whether elevated CA 19-9 levels can be considered a non casual event in chronic liver disease and whether a correlation can be found between CA 19-9 levels and the severity of the disease. METHODS: 116 patients have been recruited (76 m, 40 f, average 54 years); 56 patients were affected by CH and 60 by hepatic cirrhosis (Child A). All patients were HCV+, genotype 1b. Patients positive to CA 19-9 high levels were subjected to abdominal echography, EGDS, colonscopy, abdominal CT. RESULTS: Fifty two percent presented high levels of CA 19-9. None was affected by intestinal or pancreatic neoplasia, or colestatic icterus. CA 19-9 levels were elevated in 46% of patients with chronic hepatitis, and in 54% in patients with hepatic cirrhosis. Furthermore, CA 19-9 levels in hepatic cirrhosis compared to CA 19-9 levels in chronic hepatitis was statistically significant (P>0.007). CONCLUSION: Increased serum levels of CA 19-9 are frequent in chronic viral hepatitis; this often does not indicate a contemporary neoplastic disease and correlates in a statistically significant way (P>0.007) with the severity of the disease.

[A case of overlap syndrome: autoimmune idiopathic hepatitis/pulmonary idiopathic hypertension]. / Un caso di Overlap Sindrome: epatite autoimmune/ipertensione polmonare idiopatica.

In medical practice we frequently encounter autoimmune syndromes, called "overlap-syndromes," which are of difficult nosographic classification because of the presence of sero-immunologic and clinical features common to various diseases having an autoimmune pathogenesis. Some of these syndromes have already been extensively described in scientific literature such as, for example, the presence of clinical and biohumoral alterations with hepatic and extrahepatic involvement, in the course of viral and autoimmune chronic hepatitis. The described clinical case can be classified as a new "overlap syndrome": Type 1 autoimmune hepatitis (AIH)/Primary pulmonary hypertension (PPH). Although the presence of pulmonary hypertension has been extensively described in the course of various connective tissue diseases (S.L.E., Mixed Connective Tissue Disease, Scleroderma, Hashimoto's Thyroiditis, Sjögren's Syndrome), in recent scientific literature, the association is quite rare. The interest in the described clinical case lies both in the possibility to classify it in the context of a more complex "overlap syndrome" AIH/PPH and in the correlated diagnostic and therapeutic implications. Therefore, in cases of primary pulmonary hypertension, a thorough immunological and hepatic functionality study is always recommended in order to ensure an early diagnosis and a prompt AIH treatment, thus warding off the risk of a rapid progression in cirrhosis.

[Hepatic iron, iron depletion and response to therapy with peg-Interferon and Ribavirin in chronic hepatitis C. Pilot study]. / Ferro epatico, ferrodeplezione e risposta alla terapia con peg-Interferone e Ribavirina nell'epatite cronica C. Studio pilota.

AIM: To estimate whether pretreatment serum iron levels, the HIC (hepatic iron concentration) and the distribution of hepatic iron identify the long-term "responders" and "non-responders" to therapy with peg-IFN and RBV, and whether the addition of phlebotomy could increase the likelihood of therapeutic response. PATIENTS AND METHODS: 45 subjects with chronic hepatitis C were taking peg-IFN alpha-2a 180 microg once a week and RBV 1000 mg/die. The "responders" continued therapy with peg-IFN plus RBV, while, the "non-responders" were subjected to phlebotomy. After two weeks and subsequently every month the patients were subjected to blood test and clinical appraisal. RESULTS: Hepatic iron storage meaningfully conditions the outcome of therapy with peg-IFN and RBV, its reduction by phlebotomy favourably correlates with response to treatment and, at last, the semiquantitative histological appraisal would have to be included in the pre-treatment work-up of patients with chronic hepatitis C. CONCLUSIONS: The study results, even though obtained on a small size of cases, allow to conclude that serum corporeal iron evaluation underestimates the real hepatic iron concentration; the hepatic iron concentration, in turn, negatively conditions the response to therapy with peg-IFN and RBV (by reducing the percentage of the fast virological response). Lastly, iron removal by phlebotomy favourably correlates with the response to treatment.

[HAV infection in patients with chronic hepatitis C]. / Infezione da HAV in pazienti con epatite cronica HCV-correlata.

AIM: In most cases, hepatitis A virus (HAV) infection causes a self-limiting benign acute hepatitis which confers permanent acquired immunity. However, in patients with pre-existing chronic hepatitis, HAV superinfection can cause acute hepatitis with severe progression leading to a fulminant form or linked to the risk of a rapid deterioration of hepatic function. For such a reason, some Authors recommend anti-HAV vaccination for subjects with HCV-correlated chronic hepatitis before the initiation of peg-Interferon and Ribavirin treatment. Subsequently, the real prevalence of IgG anti-HAV antibodies in patients with HC HCV-related and in healthy subjects from Eastern Sicily has been verified. PATIENTS AND METHODS: In 254 subjects affected by HC HCV-related it has been carried out the research of antibodies IgG and IgM anti HAV. The control group was formed by 685 non hepatopathic subjects, subdivided in range of ages. RESULTS: 97.64% out of the patients affected by HC HCV related exhibit antibodies IgG anti HAV, while only 2.36% of them was negative. The prevalence of infection in the control group has been stratified in relation to different ranges of age of the people taken into consideration. CONCLUSIONS: The results obtained in this study performed in our geographical area, let us to suggest that it is not necessary the anti HAV vaccination during the phase of pre-treatment for HC HCV-related.

Markers of chemoradiation resistance in patients with locally advanced head and neck squamous cell carcinoma, treated by intra-arterial carboplatin and concurrent radiation.

The onset of chemo- and/or radio-resistance in tumour cells is one of the main causes of failure of integrated treatment protocols combining intra-arterial administration of platinum derivatives and radiotherapy, and is associated with recurrent disease and/or distant metastases. In the present study, the expression of a series of markers of chemo- and/or radio-resistance was investigated in 21 patients with advanced squamous cell carcinoma of the head and neck treated with combined intra-arterial carboplatin and radiotherapy. The results were correlated with local response to treatment, recurrence and overall and disease-free survival. In non-responders or in patients presenting recurrence, caspase 8 was significantly (p 0.05) under-expressed while p-Gp (p 0.035) and MDR-3 (p 0.049) were significantly over-expressed. Tumours with unfavourable outcome more frequently over-expressed two or more anti-apoptotic factors (p-53, BCL-2, BCL-x) (p 0.01). Patients with shorter overall survival, significantly overexpressed p53 (p 0.04), LRP (p 0.038) and a larger number of trans-membrane transport proteins compared with those who survived more than one year (p 0.013). Finally, patients with the shortest disease-free survival presented over-expression of p53 (p 0.027) and BCL-x (p 0.023). Further studies are necessary to confirm the possibility, in a future perspective, of using a panel of markers of chemo- and radio-resistance to identify those patients potentially sensitive to the treatment and to avoid patients at high risk of resistance from being submitted to ineffective and toxic treatment protocols.

The importance of the reproducibility of oropharyngeal swallowing in amyotrophic lateral sclerosis. An electrophysiological study.

OBJECTIVE: To investigate electrophysiologically the reproducibility of oropharyngeal swallowing in patients with ALS. METHODS: We enrolled 26 ALS patients, both with and without clinical signs of dysphagia, and 30 age-matched controls. The reproducibility of the electrophysiological signals related to the oral phase (electromyographic activity of the submental/suprahyoid muscles) and the pharyngeal phase (laryngeal-pharyngeal mechanogram) of swallowing across repeated swallows was assessed. To do this we computed two similarity indexes (SI) by using previously described mathematical algorithms. RESULTS: The reproducibility of oropharyngeal swallowing was significantly reduced both in patients with and in those without clinical signs of dysphagia, with more marked alterations being detected in the dysphagic group. The SI of both phases of swallowing, oral and pharyngeal, correlated significantly with dysphagia severity and disease severity. CONCLUSIONS: In ALS different pathophysiological mechanisms can alter the stereotyped motor behaviors underlying normal swallowing, thus reducing the reproducibility of the swallowing act. A decrease in swallowing reproducibility could be a preclinical sign of dysphagia and, beyond a certain threshold, a pathological hallmark of oropharyngeal dysphagia. SIGNIFICANCE: Electrophysiological assessment is a simple and useful tool for the early detection of swallowing abnormalities, and for the management of overt dysphagia in ALS.

Is early recurrence of hepatocellular carcinoma in HCV cirrhotic patients affected by treatment with direct-acting antivirals? A prospective multicentre study.

BACKGROUND: Data on HCV-related hepatocellular carcinoma (HCC) early recurrence in patients whose HCC was previously cured, and subsequently treated by direct-acting antivirals (DAAs), are equivocal. AIM: To assess the risk of HCC early recurrence after DAAs exposure in a large prospective cohort of HCV-cirrhotic patients with previous successfully treated HCC, also looking for risk factors for cancer early recurrence. METHODS: We enrolled 143 consecutive patients with complete response after curative treatment of HCC, subsequently treated with DAAs and monitored by the web-based RESIST-HCV database. Clinical, biological, and virological data were collected. The primary endpoint was the probability of HCC early recurrence from DAA starting by Kaplan-Meier method. RESULTS: Eighty-six per cent of patients were in Child-Pugh class A and 76% of patients were BCLC A. Almost all patients (96%) achieved sustained virological response. Twenty-four HCC recurrences were observed, with nodular or infiltrative pattern in 83% and 17% of patients, respectively. The 6-, 12- and 18-month HCC recurrence rates were 12%, 26.6% and 29.1%, respectively. Main tumour size and history of prior HCC recurrence were independent risk factors for HCC recurrence by Cox multivariate model. CONCLUSIONS: Probability of HCC early recurrence in patients who had HCC previously cured remains high, despite HCV eradication by DAAs. Risk was comparable but not higher to that reported in literature in DAA-untreated patients. Previous HCC recurrence and tumour size can be used to stratify the risk of HCC early recurrence. Further studies are needed to assess impact of DAAs on late recurrence and mortality.

The combined endoscopic therapy (band ligation and sclerosis) in the eradication of the esophageal varices in the cirrhotic patient: our experience.

AIM: In course of liver cirrhosis, esophageal varices develop with an incidence of 8-15% a year, and they constitute a sign of seriousness of portal hypertension. The risk of bleeding is estimated around 10-15% a year. The varices hemorrhage causes a high rate of mortality (around 30-35% for every hemorrhagic event). It follows that it is necessary to plan prophylactic strategies for all the cirrhotic patients, who are at risk of bleeding, or have already bled. Medical treatment with beta-blockers is indicated in the prophylaxis of the first bleeding, while endoscopic treatment represents now the most effective methodology either in acute bleeding, or in the prophylaxis of hemorrhage relapses. The available endoscopic methodologies are the sclerosis or band ligation of esophageal varices. However, unanimous consent about the greater effectiveness of a methodology compared to the other one doesn't exist. As far as the varices eradication is concerned, the authors have done a research to verify if the combined techniques, proposed in various studies appeared in literature, can have some advantages, in comparison with the single methodologies. METHODS: Thirty-seven patients have been treated: 27 only with sclerosis and 10 with combined methodology (band-ligation followed by sclerosis of the small residual varices). RESULTS: The group treated with the combined therapy have shown a reduction in relapses and in the main side effects and a better patients' compliance. CONCLUSIONS: The combination of the two methodologies can have some advantages as for security, easiness of execution, reduction in complications, in varices relapse and, therefore, in the hemorrhagic relapses.