Curative versus palliative treatments for recurrent hepatocellular carcinoma: a multicentric weighted comparison

BackgroundManagement of recurrence after surgery for hepatocellular carcinoma (rHCC) is still a debate. The aim was to compare the Survival after Recurrence (SAR) of curative (surgery or thermoablation) versus palliative (TACE or Sorafenib) treatments for patients with rHCC.MethodsThis is a multicentric Italian study, which collected data between 2007 and 2018 from 16 centers. Selected patients were then divided according to treatment allocation in Curative (CUR) or Palliative (PAL) Group. Inverse Probability Weighting (IPW) was used to weight the groups.Results1,560 patients were evaluated, of which 421 experienced recurrence and were then eligible: 156 in CUR group and 256 in PAL group. Tumor burden and liver function were weighted by IPW, and two pseudo-population were obtained (CUR = 397.5 and PAL = 415.38). SAR rates at 1, 3 and 5 years were respectively 98.3%, 76.7%, 63.8% for CUR and 91.7%, 64.2% and 48.9% for PAL (p = 0.007). Median DFS was 43 months (95%CI = 32-74) for CUR group, while it was 23 months (95%CI = 18-27) for PAL (p = 0.017). Being treated by palliative approach (HR = 1.75; 95%CI = 1.14–2.67; p = 0.01) and having a median size of the recurrent nodule>5 cm (HR = 1.875; 95%CI = 1.22–2.86; p = 0.004) were the only predictors of mortality after recurrence, while time to recurrence was the only protective factor (HR = 0.616; 95%CI = 0.54–0.69; p<0.001).ConclusionCurative approaches may guarantee long-term survival in case of recurrence.     

Management of sellar and parasellar tumors becoming symptomatic during pregnancy: a practical algorithm based on multi-center experience and systematic literature review

Introduction

Sellar/parasellar tumors (SPTs) very rarely become symptomatic during pregnancy. No specific guidelines exist for their management, that is extremely challenging as mother and fetus health can be jeopardized.

Materials and methods

Data of patients with SPTs becoming symptomatic during pregnancy treated at two Italian referral Centers were retrospectively collected. Systematic literature review was also performed.

Results

Our series consisted of 6 cases, 3 meningiomas, 1 ACTH-secreting adenoma, 1 pituicytoma and 1 craniopharyngioma. Mean age at presentation was 33.6?±?6.0 years. Five patients complained of visual disturbances, associated with headache in one case, that occurred between gestation week (GW) 22 and 34. In 5 cases, pregnancy was uneventful with the delivery of a healthy baby between GW 33 and 35, followed by endoscopic surgical tumor exeresis (n?=?4) or proton bean therapy (n?=?1). Another patient presented with stigmata typical of Cushing’s syndrome and rapidly worsening pre-eclampsia, that required pregnancy interruption and adenomectomy. Based on personal and literature cases, a practical algorithm was proposed to help clinicians dealing with these patients.

Conclusions

SPTs becoming symptomatic in pregnancy deserve careful monitoring and multidisciplinary management. Overall, wait-and-see approach is suggested, reserving surgery to patients with rapidly progressive/life-threatening situations, significant risk of permanent neurological impairment or malignant lesions.

     

From microbiota toward gastro-enteropancreatic neuroendocrine neoplasms: Are we on the highway to hell?

Gut microbiota is represented by different microorganisms that colonize the intestinal tract, mostly the large intestine, such as bacteria, fungi, archaea and viruses. The gut microbial balance has a key role in several functions. It modulates the host’s metabolism, maintains the gut barrier integrity, participates in the xenobiotics and drug metabolism, and acts as protection against gastro-intestinal pathogens through the host’s immune system modulation. The impaired gut microbiota, called dysbiosis, may be the result of an imbalance in this equilibrium and is linked with different diseases, including cancer. While most of the studies have focused on the association between microbiota and gastrointestinal adenocarcinomas, very little is known about gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). In this review, we provide an overview concerning the complex interplay between gut microbiota and GEP NENs, focusing on the potential role in tumorigenesis and progression in these tumors.

     

Effect of UV Irradiation and TiO2-Photocatalysis on Airborne Bacteria and Viruses: An Overview

Current COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has put a spotlight on the spread of infectious diseases brought on by pathogenic airborne bacteria and viruses. In parallel with a relentless search for therapeutics and vaccines, considerable effort is being expended to develop ever more powerful technologies to restricting the spread of airborne microorganisms in indoor spaces through the minimization of health- and environment-related risks. In this context, UV-based and photocatalytic oxidation (PCO)-based technologies (i.e., the combined action of ultraviolet (UV) light and photocatalytic materials such as titanium dioxide (TiO₂)) represent the most widely utilized approaches at present because they are cost-effective and ecofriendly. The virucidal and bactericidal effect relies on the synergy between the inherent ability of UV light to directly inactivate viral particles and bacteria through nucleic acid and protein damages, and the production of oxidative radicals generated through the irradiation of the TiO₂ surface. In this literature survey, we draw attention to the most effective UV radiations and TiO₂-based PCO technologies available and their underlying mechanisms of action on both bacteria and viral particles. Since the fine tuning of different parameters, namely the UV wavelength, the photocatalyst composition, and the UV dose (viz, the product of UV light intensity and the irradiation time), is required for the inactivation of microorganisms, we wrap up this review coming up with the most effective combination of them. Now more than ever, UV- and TiO₂-based disinfection technologies may represent a valuable tool to mitigate the spread of airborne pathogens.     

Migrainous Infarction in a Patient With Sporadic Hemiplegic Migraine and Cystic Fibrosis: A 99mTc-HMPAO Brain SPECT Study

Genetic mutations of sporadic hemiplegic migraine (SHM) are mostly unknown. SHM pathophysiology relies on cortical spreading depression (CSD), which might be responsible for ischemic brain infarction. Cystic fibrosis (CF) is caused by a monogenic mutation of the chlorine transmembrane conductance regulator (CFTR), possibly altering brain excitability. We describe the case of a patient with CF, who had a migrainous stroke during an SHM attack. A 32-year-old Caucasian male was diagnosed with CF, with heterozygotic delta F508/unknown CFTR mutation. The patient experiences bouts of coughing sometimes triggering SHM attacks with visual phosphenes, aphasia, right-sided paresthesia, and hemiparesis. He had a 48-hour hemiparesis triggered by a bout of coughing with hemoptysis, loss of consciousness, and severe hypoxia-hypercapnia. MRI demonstrated transient diffusion hyperintensity in the left frontal-parietal-occipital regions resulting in a permanent infarction in the primary motor area. Later, a brain perfusion SPECT showed persistent diffuse hypoperfusion in the territories involved in diffusion-weighted imaging alteration. Migrainous infarction, depending on the co-occurrence of 2 strictly related phenomena, CSD and hypoxia, appears to be the most plausible explanation. Brain SPECT hypoperfusion suggests a more extensive permanent neuronal loss in territories affected by aura. CF may be then a risk factor for hemiplegic migraine and stroke since bouts of coughing can facilitate brain hypoxia, triggering auras.     

bcl-2 overexpression promotes myocyte proliferation

To determine the influence of Bcl-2 on the developmental biology of myocytes, we analyzed the population dynamics of this cell type in the heart of transgenic (TG) mice overexpressing Bcl-2 under the control of the alpha-myosin heavy chain promoter. TG mice and non-TG (wild type, WT) mice were studied at 24 days, 2 months, and 4 months after birth. Bcl-2 overexpression produced a significant increase in the percentage of cycling myocytes and their mitotic index. These effects were strictly connected to the expression of the transgene, as demonstrated in isolated myocytes. The formation of mitotic spindle and contractile ring was identified in replicating cells. These typical aspects of mitosis were complemented with the demonstration of karyokinesis and cytokinesis to provide structural evidence of cell division. Apoptosis was low at all ages and was not affected by Bcl-2. The higher cell replication rate in TG was conditioned by a decrease in the expression of the cell-cycle inhibitors, p21(WAF1) and p16(INK4a), and by an increase in Mdm2-p53 complexes. In comparison with WT, TG had 0.4 x 10(6), 0.74 x 10(6), and 1.2 x 10(6) more myocytes in the left ventricle at 24 days, 2 months, and 4 months, respectively. Binucleated myocytes were 12% and 25% larger in WT than in TG mice at 2 and 4 months of age. Taken together, these observations reveal a previously uncharacterized replication-enhancing function of Bcl-2 in myocytes in vivo in the absence of stressful conditions.     

Somatostatin receptors 1, 2, and 5 cooperate in the somatostatin inhibition of C6 glioma cell proliferation in vitro via a phosphotyrosine phosphatase-eta-dependent inhibition of extracellularly regulated kinase-1/2

Somatostatin inhibits cell proliferation through the activation of five receptors (SSTR1-5) expressed in normal and cancer cells. We analyzed the role of individual SSTRs in the antiproliferative activity of somatostatin in C6 rat glioma cells. Somatostatin dose-dependently inhibited C6 proliferation, an effect mimicked, with different efficacy or potency, by BIM-23745, BIM-23120, BIM-23206 (agonists for SSTR1, -2, and -5) and octreotide. The activation of SSTR3 was ineffective, although all SSTRs are functionally active, as demonstrated by the inhibition of cAMP production. All SSTRs induced cytostatic effects through the activation of the phosphotyrosine phosphatase PTPeta and the inhibition of ERK1/2. For possible synergism between SSTR subtypes, we tested the effects of the combined treatment with two agonists (SSTR1+2 or SSTR2+5) or bifunctional compounds. The simultaneous activation of SSTR1 and SSTR2 slightly increased the efficacy of the individual compounds with an IC50 in between the single receptor activation. SSTR2+5 activation displayed a pattern of response superimposable to that of the SSTR5 agonist alone (low potency and higher efficacy, as compared with BIM-23120). The simultaneous activation of SSTR1, -2, and -5 resulted in a response similar to somatostatin. In conclusion, the cytostatic effects of somatostatin in C6 cells are mediated by the SSTR1, -2, and -5 through the same intracellular pathway: activation of PTPeta and inhibition of ERK1/2 activity. Somatostatin is more effective than the individual agonists. The combined activation of SSTR1 and -2 shows a partial synergism as far as antiproliferative activity, whereas SSTR2 and -5 activation results in a response resembling the SSTR5 effects.     

Qualitative and quantitative evaluation of mitral valve morphology by intraoperative volume-rendered three-dimensional echocardiography

BACKGROUND AND AIM OF THE STUDY: Two-dimensional echocardiography (2DE) performed to evaluate mitral valve anatomy during valve repair has certain limitations and pitfalls. The study aim was to assess the feasibility, accuracy and incremental value of three-dimensional echocardiography (3DE), coupled with 2DE in evaluating mitral valve structure, before and after repair and pericardial posterior annuloplasty. METHODS: The site and extent of mitral valve prolapse, systolic and diastolic changes of mitral annular area were evaluated using 2D and 3D transesophageal echocardiography (TEE), both pre- and postoperatively in 34 patients before and after mitral valve repair and pericardial posterior annuloplasty. RESULTS: Concordance between 2DE and surgery in evaluating prolapsing mitral valve scallops was 76% for the anterior leaflet and 75% for the posterior leaflet; for 3DE and surgery, concordance was 87% and 93% respectively. There was a significant reduction in maximal and minimal annular area after surgery, with a statistically significant difference between systolic-diastolic changes. CONCLUSION: 3DE, coupled with 2DE, is feasible and accurate in delineating the extent and location of prolapsing scallops of the mitral valve. The combined approach is also valuable in planning mitral valve surgery and evaluating the mitral valve annulus in vivo.