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The clinical usefulness of alpha-fetoprotein (AFP) in hepatocellular carcinoma (HCC) management is debatable.To assess, in a large multi-centric survey, diagnostic and prognostic reliability of AFP, predictive factors, and any correlation with the tumor immunophenotype.A total of 1,158 patients with HCC were analyzed with reference to serum AFP levels at diagnosis. We evaluated: HCC grading, histotype, and size; Okuda, tumor-nodes-metastases (TNM), and Child-Pugh scores; liver function, symptoms, presence of metastases or portal thrombosis, etiology, survival, and treatment. In 66 patients with histological diagnosis, the pathologists evaluated p53 overexpression, MIB 1 labeling index, BCL-2 positive cells (index of apoptosis), and CD44 (adhesion molecule) positivity.Patients were divided into three AFP groups: normal (20 ng/mL) [46%], elevated (21-400 ng/mL) [36%], and diagnostic (400 ng/mL) [18%]. Statistical correlations were significant for: weight loss (p= 0.0056), pain (p= 0.0025), Child-Pugh score (p= 0.001), tumor size, Okuda's and TNM stages, metastases, thrombosis, type of treatment (all p0.0001), and female sex (p0.004). AFP correlated with survival overall, in patients untreated, transplanted, or undergoing locoregional treatments; but not in those surgically treated. In the discriminant analysis, the related variables were size, female sex, Child-Pugh score, TNM staging (steps 1-4). When using the receiver operating characteristic curve, the prognostic reliability of AFP was limited with area under the curve of 0.59. Finally, patients with low expression of BCL2 had high AFP levels (p0.05). AFP positively correlated with Edmonson score (p0.0001).The evaluation of this large series of HCC patients allowed us to: confirm the low sensitivity (54%) of AFP in the diagnosis of HCC and its prognostic value, albeit limited, being tumor size, female sex (intriguingly enough), Child-Pugh score, and TNM staging independent predictors.

Background/aims. The prognosis of hepatocellular carcinoma (HCC) on cirrhosis is hard to predict as it depends on tumour stage, underlying liver disease, type of treatment and, possibly, biological factors of the tumour itself. Methods. We prospectively evaluated the survival of 91 consecutive patients with HCC on cirrhosis, diagnosed between January 1998 and December 1999. Clinical features and histological/biological aspects, including histotype, grade, p53 overexpression, cytoproliferation and apoptotic markers were analysed. Results. Child-Pugh (P = 0.01), Okuda (P < 0.0001), Cancer of the Liver Italian Program (CLIP) staging (P

Background Sorafenib has shown survival benefits in patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh (CP) class A liver function. There are few prospective data on sorafenib in patients with HCC and CP class B. Patients and methods A consecutive prospective series of 300 patients with CP class A or B HCC were enrolled in a dual-phase trial to determine survival and safety data according to liver function (class A or B) in patients receiving oral sorafenib 800 mg daily. [Results of this study were presented in part at the ASCO 2012 Gastrointestinal Cancers Symposium, 19–21 January 2012. J Clin Oncol 2012; 30 (Suppl 4): abstract 306.] Results Overall progression-free survival (PFS), time to progression (TTP) and overall survival (OS) were 3.9, 4.1 and 9.1 months, respectively. For patients with CP class A versus B status, PFS was 4.3 versus 2.1 months, TTP was 4.2 versus 3.8 months and OS was 10.0 versus 3. 8 months. Extrahepatic spread was associated with worse outcomes but taken together with CP class, liver function played a greater role in reducing survival. Adverse events for the two CP groups were similar. Conclusion Although patients with HCC and CP class B liver function have poorer outcomes than those with CP class A function, data suggest that patients with CP class B liver function can tolerate treatment and may still benefit from sorafenib.

Objective: To determine whether exposure to antiepileptic drugs during pregnancy is associated with poor fetal outcomes (anomalies and death) and to assess the relative risks with phenobarbital, phenytoin sodium, and carbamazepine. Design: The design was a prospective case-control cohort study of pregnant women with epilepsy and their offspring. Outcomes were compared with those of a control group of 355 healthy women and their offspring. Setting: The obstetrics service at Los Angeles County/University of Southern California Medical Center, Los Angeles, a large, inner-city, teaching hospital. Patients: Two hundred eleven subjects who were pregnant during the years 1987 through 1990,174 of whom were delivered of infants, were available for analysis. A control group of 355 healthy women and their offspring from the same hospital were randomly selected from a computerized database. Interventions: None. Main Outcome Measure: Anomalies and fetal death were the primary outcome measures. Results: Offspring of women with epilepsy who were exposed to antiepileptic drugs had a higher rate of fetal death and anomalies than did the control population ( P =.001). Abnormal outcomes were associated with the three major antiepileptic drugs (carbamazepine, phenytoin, and phenobarbital). In terms of abnormal outcome (death and anomalies), phenobarbital was associated with the highest relative risk, phenytoin with intermediate relative risk, and carbamazepine with the lowest relative risk ( P =.019). Numbers were insufficient for assessment of risk associated with valproic acid. Conclusion: All three major antiepileptic drugs (phenobarbital, phenytoin, and carbamazepine) are associated with an increased risk of fetal death and anomalies. We found phenobarbital to be most associated with poor pregnancy outcome.

Lidocaine was efficacious in 2 patients with refractory status epilepticus (RSE) unresponsive to several antiepileptic drugs (AEDs), including high-dose barbiturates. We confirmed the efficacy of lidocaine with, for the first time in adults, continuous EEG monitoring. Lidocaine, when properly used, may be a treatment option in RSE.

Background and aim. Earlier diagnosis and more effective treatments are improving the survival of patients with HCC. Moreover, the natural history of HCC patients is different from that patients with non-neoplastic indications for liver transplantation. This issue becomes critical to provide an equitable allocation policy to patients listed for transplantation. UNOS adopted a MELD-based policy that assigns the native MELD for patients with stage I HCC and 22 points for patients stage II HCC listed for Liver Transplant (LT), with an additional three points added every 3 months of waiting time in list for the latter. Organs are then assigned on the basis of the MELD score, irrespective of the indication. In countries outside the UNOS area, allocation for HCC patients still misses uniformity. Aim. The aim of the study was to generate an updated prognostic model for HCC applicable to organ allocation. Material and methods. We analysed disease progression (death or progression of HCC beyond T2 stage) in a cohort of 177 consecutive patients that presented with HCC inside the Milan criteria. Patients were treated according to the BCLC algorithm and prospectively followed by imaging every 3 months; 76 patients (43%) were listed for transplantation according to AISF/CNT guidelines. Transplanted patients were censored at the time of transplantation. Results. Median follow-up was 16 months. HCC progressed beyond T2 stage in 75 cases; 8 patients died while in T2 stage and 68 were transplanted. To verify the ability of the UNOS policy to predict HCC progression rate (PR), we compared the expected PR according to the UNOS policy with the observed PR for the respective population at risk. The current policy resulted in a large overestimation of PR in T2 patients. Two sensitivity analyses were conducted to identify risk factor (RF) for progression using the log-rank method: in the first one, transplanted patients were considered as disease progression; in the second one, only non-transplanted patients were analysed. RF significant in any analysis was considered for multivariable analysis. RF with the strongest relationship to progression included tumor persistence after local therapy or recurrence inside Milan criteria (HR 2.52–3.16; p < 0.0001). Using strongest RF for progression and the patient's natural MELD, an adjusted model applicable to organ allocation was generated, which decreased the discrepancy between expected and observed PR. Conclusions. Tumor persistence/recurrence inside Milan criteria after treatment strongly predicted the risk of tumor progression beyond Milan criteria. The current MELD exception largely overestimates progression in T2 patients treated according to BCLC. An adjusted model that begins with the patient's natural MELD, and stratifies progressive risk according to the response to local treatment, better captures the PR of T2 HCC

The aim of this review was to assess the correct clinical management of hepatocellular carcinoma (HCC). Following the diagnosis, the correct choice of treatment must take into account both the anatomical/biological features of HCC and the functional status of the underlying cirrhosis. As of today, only the application of the BCLC scoring system, which stratifies patients according to HCC staging and degree of liver disease in a process leading to a specific treatment, has shown the best results in terms of survival.

Surgery (resection or transplantation) is the treatment of choice for early hepatocellular carcinoma (HCC) but unfortunately it is feasible in only a minority of patients.1 Local percutaneous ablation has therefore dramatically increased in importance and radiofrequency thermal ablation (RFTA) has been shown in recent reports to have global or disease free survival better than that reported for percutaneous ethanol injection (PEI).2 The recent report in Gut apparently also supports the superiority, albeit small, of RFTA over PEI or acetic acid injection in a randomised prospective controlled study ( Gut 2005; 54 :1151–6). Nevertheless, not all agree on the efficacy of RFTA3 and major complications have been described.4 In Lin et al ’s study (Gut …

Variant liver oestrogen receptor transcripts in hepatocellular carcinoma are associated with aggressive clinical course and unresponsiveness to tamoxifen. To evaluate the impact on survival and on tumour growth of megestrol (progestin drug acting at post-receptorial level) we enrolled 45 patients with HCC characterized by variant liver oestrogen receptors in a prospective, randomized study with megestrol vs. placebo. Presence of variant oestrogen receptors was determined by RT/PCR. 24 patients were randomized to no treatment and 21 to therapy with megestrol 160 mg day(-1). Results were analysed by Kaplan-Meier and Cox methods. Survival of hepatocellular carcinoma characterized by variant oestrogen receptors was extremely poor (median survival 7 months); megestrol significantly improved survival (18 months) (P = 0.0090). Tumour growth at one year was significantly slowed down in megestrol-treated patients (P = 0.0212). Bilirubin levels, presence of portal thrombosis, HBV aetiology and treatment were identified at univariate analysis as factors significantly associated with survival; at multivariate analysis, only megestrol therapy (P = 0.0003), presence of HBV infection (P = 0.0009) and presence of portal vein thrombosis (P = 0.0051) were factors independently related with survival. (1) Megestrol slows down the aggressive tumour growth of patients with hepatocellular carcinoma characterized by variant estrogen receptors and (2) is also able to favourably influence the course of disease, more than doubling median survival.

This paper reports the case of a woman, who underwent surgery because of cholelithiasis, with intraoperative finding of prehepatic portal hypertension from portal vein thrombosis ("portal cavernoma") with healthy liver, later confirmed by angiographic studies. This rare pathologic association carries a higher risk of major operative complications; therefore the Authors agree with the general belief that, for these cases, biliary tract surgery should be as simple and safe as possible. In the case of preoperative diagnosis of biliary disease associated with portal cavernoma, should a surgical approach on the biliary tract be required, we agree on the advisability of performing a shunting procedure before any kind of biliary surgery. In case of variceal bleeding endoscopic sclerotherapy will be the first choice; surgical procedures (shunting) should be seen as a second choice in case of rebleeding after sclerotherapy.

The prolapse of vaginal vault after hysterectomy is a rather common event, whereas ileal evisceration and intestinal occlusion following a complete rupture of an inverted vaginal vault is extremely rare. The Authors report a case successfully treated using a modified Feldman and Birnbaum colposacropexy. The technique, which takes into account pathophysiologic mechanisms of vaginal prolapse, is described in detail and involves the use of a Dacron mesh.

ackground. Staging systems for HCC are essential to assess prognosis, to uide the therapeutic approach and to design clinical trials. So far, no conensus is achieved on which of the several proposed staging system performs etter. im. To compare the three main staging systems (TNM, CLIP and BCLC) or which external validation data are present, using a large cohort of HCC atients followed prospectively at a single referral centre. ethods. Demographic, clinical and histological data were prospectively ollected, together with liver imaging, at baseline and at 3-month intervals fter enrolment, in 327 consecutive HCC patients referred to our Unit from anuary 2000 to June 2005. HCC was diagnosed according with EASL criteia (histologically confirmed in 69%). Median follow-up was 2 years. 71 pts ere resected, 46 pts underwent liver transplantation inside Milan Criteria age

SUMMARY: A 20-year-old woman developed a systemic lupus erythematosus (SLE)-like syndrome and a positive antinuclear antibody (ANA) soon after initiation of carbamazepine (CBZ) therapy. Symptoms and serology became normal after CBZ was discontinued. CBZ-induced SLE is an important but underecognized phenomenom. RESUMEN Una mujer de 20 anos de edad desarrollo un sindrome parecido a un Lupus Eritematoso Sistemico (SLE) y anticuerpos antinucleares (ANA) positivos tras la initiateon de un tratamiento con carbamacepina (CBZ). Los sintomas y las serologias se normalizaron despues de interrumpir la CBZ. La CBZ induce un importante pero poco reconocido cuadro de SLE. ZUSAMMENFASSUNG Eine 20 jahrige Frau entwickelte ein Lupus-erythematodes ahnliches Syndrom mit positiven antinuklearen Faktoren kurz nach Beginn der Carbamazepintherapie. Symptome und Serologie normalisierten sich nach Absetzen von CBZ. Der CBZ-induzierte LE stellt ein wichtiges aber zu weniges beachtetes Phanomen dar.

A critical overview of the major studies of coma prognosis and a theoretical analysis of the inherent limitations of even a methodologically ideal study lead to the conclusion that no existing or realistic future study can generate early predictors of poor outcome with a sufficiently low risk of falsepositive error to justify withdrawal of life-sustaining treatment. Early prognostic criteria can, however, serve a variety of other useful purposes.

We describe a case of reversible encephalopathy caused by the recently released anticancer drug Ifosfamide. The clinical course, role of EEG in monitoring and predicting encephalopathy, and putative mechanism of neurotoxicity is discussed. Short infusion times and/or prior CNS disease may increase the risk of encephalopathy.

As desirable as it might be to predict early in the course of coma whether a patient will do well or poorly, all studies of coma prognosis are plagued by inherent methodologic problems that tend to diminish the utility of the derived criteria: especially the tendency of poor prognoses to be self-fulfilling, the rapid drop-off in patient population due to death from nonneurologic causes, and the need to lump, for the sake of statistical significance, outcome categories that ought to be kept distinct for purposes of ethical decision making. Even for a methodologically ideal study, if 100 per cent of the N patients fulfilling a particular criterion experienced the same poor outcome, the probability of a false prediction of poor outcome in the next patient meeting that criterion is approximately 1/(N + 2), which is hardly negligible for a realistically sized study. Moreover, there is a 50 per cent chance of at least one false-positive prediction among the next (N + 1) patients fulfilling the criterion. Given this inherent unreliability of early predictors for individual patients, given that decisions to continue life support are reversible, whereas decisions to withdraw it are usually not, and given that the death of a patient with potential for recovery is a more serious error than the (typically) transient prolongation of life of a patient destined soon to die anyway or (much less commonly) to remain in a chronic vegetative state, it would seem prudent to continue life support for all patients during the first few weeks or months of coma or vegetative state, regardless of early indicators of poor outcome. Early prognostication can still serve other useful purposes, however, including the counseling of families, triage and DNR decisions, and future clinical investigations of brain-resuscitative measures.

ObjectivePostacute COVID-19 syndrome (PACS) is an emerging entity characterised by a large array of manifestations, including musculoskeletal complaints, fatigue and cognitive or sleep disturbances. Since similar symptoms are present also in patients with fibromyalgia (FM), we decided to perform a web-based cross-sectional survey aimed at investigating the prevalence and predictors of FM in patients who recovered from COVID-19.MethodsData were anonymously collected between 5 and 18 April 2021. The collection form consisted of 28 questions gathering demographic information, features and duration of acute COVID-19, comorbid diseases, and other individual’s attributes such as height and weight. The American College of Rheumatology (ACR) Survey Criteria and the Italian version of the Fibromyalgia Impact Questionnaire completed the survey.ResultsA final sample of 616 individuals (77.4% women) filled the form 6±3 months after the COVID-19 diagnosis. Of these, 189 (30.7%) satisfied the ACR survey criteria for FM (56.6% women). A multivariate logistic regression model including demographic and clinical factors showed that male gender (OR: 9.95, 95% CI 6.02 to 16.43, pConclusionOur data suggest that clinical features of FM are common in patients who recovered from COVID-19 and that obesity and male gender affect the risk of developing post-COVID-19 FM.