ABSTRACT
This study presents the mineralogy and strontium isotope ratio (87Sr/86Sr) of 21 pathological biominerals (bladder and kidney stones) collected from patients admitted between 2018 and 2020 at the Department of Urology of the San Pio Hospital (Benevento, southern Italy). Urinary stones belong to the calcium oxalate, purine or calcium phosphate mineralogy types. Their corresponding 87Sr/86Sr range from 0.707607 for an uricite sample to 0.709970 for a weddellite one, and seem to be partly discriminated based on the mineralogy. The comparison with the isotope characteristics of 38 representative Italian bottled and tap drinking waters show a general overlap in 87Sr/86Sr with the biominerals. However, on a smaller geographic area (Campania Region), we observe small 87Sr/86Sr differences between the biominerals and local waters. This may be explained by external Sr inputs for example from agriculture practices, inhaled aerosols (i.e., particulate matter), animal manure and sewage, non-regional foods. Nevertheless, biominerals of patients that stated to drink and eat local water/wines and foods every day exhibited a narrower 87Sr/86Sr range roughly matching the typical isotope ratios of local geological materials and waters, as well as those of archaeological biominerals from the same area. Finally, we conclude that the strontium isotope signature of urinary stones may reflect that of the environmental matrices surrounding patients, but future investigations are recommended to ultimately establish the potential for pathological biominerals as reliable biomonitoring proxies, taking into the account the contribution of the external sources of Sr.
Subject(s)
Drinking Water , Urinary Calculi , Animals , Humans , Strontium Isotopes/analysis , Isotopes , Agriculture , StrontiumABSTRACT
Wine production represents one of the most important agro-industrial sectors in Italy. Wine lees are the most significant waste in the winery industry and have high disposal and storage costs and few applications within the circular economy. In this study, anaerobic digestion and a microalgae coupled process was studied in order to treat wine lees and waste activated sludge produced within the same facility, with the aim of producing energy and valuable microalgae biomass that could be processed to recover biofuel or biostimulant. Chlorella vulgaris was cultivated on liquid digestate in a semi-continuous system without biomass recirculation. The best growth and phytoremediation performance were achieved applying a hydraulic retention time (HRT) of 20 days with a stable dry weight, lipid and protein storage of 1.85 ± 0.02 g l-1, 33.48 ± 7.54 % and 57.85 ± 10.14 % respectively. Lipid characterization highlighted the potential use in high quality biodiesel production, according to EN14214 (<12 % v/v linolenic acid). The microalgae reactor's liquid output showed high removal of ammonia (95.72 ± 2.10 %), but low organic soluble matter reduction. Further semi-continuous process optimization was carried out by increasing the time between digestate feeding and biomass recovery at HRT 10. These operative changes avoided biomass wash-out and provided a stable phytoremediation of the digestate with 84.58 ± 4.02 % ammonia removal, 33.01 ± 1.44 % sCOD removal, 38.06 ± 2.65 % of polyphenols removal.
Subject(s)
Chlorella vulgaris , Microalgae , Sewage , Anaerobiosis , Ammonia , Biofuels , Biomass , Lipids , DigestionABSTRACT
BACKGROUND: Metastatic colorectal cancer (mCRC) patients tend to have modest benefits from molecularly driven therapeutics. Patient-derived tumor organoids (PDTOs) represent an unmatched model to elucidate tumor resistance to therapy, due to their high capacity to resemble tumor characteristics. MATERIALS AND METHODS: We used viable tumor tissue from two cohorts of patients with mCRC, naïve or refractory to treatment, respectively, for generating PDTOs. The derived models were subjected to a 6-day drug screening assay (DSA) with a comprehensive pipeline of chemotherapy and targeted drugs against almost all the actionable mCRC molecular drivers. For the second cohort DSA data were matched with those from PDTO genotyping. RESULTS: A total of 40 PDTOs included in the two cohorts were derived from mCRC primary tumors or metastases. The first cohort included 31 PDTOs derived from patients treated in front line. For this cohort, DSA results were matched with patient responses. Moreover, RAS/BRAF mutational status was matched with DSA cetuximab response. Ten out of 12 (83.3%) RAS wild-type PDTOs responded to cetuximab, while all the mutant PDTOs, 8 out of 8 (100%), were resistant. For the second cohort (chemorefractory patients), we used part of tumor tissue for genotyping. Four out of nine DSA/genotyping data resulted applicable in the clinic. Two RAS-mutant mCRC patients have been treated with FOLFOX-bevacizumab and mitomycin-capecitabine in third line, respectively, based on DSA results, obtaining disease control. One patient was treated with nivolumab-second mitochondrial-derived activator of caspases mimetic (phase I trial) due to high tumor mutational burden at genotyping, experiencing stable disease. In one case, the presence of BRCA2 mutation correlated with DSA sensitivity to olaparib; however, the patient could not receive the therapy. CONCLUSIONS: Using CRC as a model, we have designed and validated a clinically applicable methodology to potentially inform clinical decisions with functional data. Undoubtedly, further larger analyses are needed to improve methodology success rates and propose suitable treatment strategies for mCRC patients.
Subject(s)
Colonic Neoplasms , Colorectal Neoplasms , Humans , Cetuximab/adverse effects , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , MutationABSTRACT
The imaging has critical responsibility in the assessment of peritoneal lesions along with estimating the overall extent. Valuing disease burden is crucial for selection of combining cytoreductive surgery (CRS) and intraperitoneal hyperthermic chemotherapy (HIPEC) treatment. An approach that combines the strength of several imaging tools and increases diagnostic accuracy, should be chosen, even if the preferred imaging tool in patients with suspected Peritoneal Carcinomatosis (PC) is CT. The outcomes of PC are mainly correlated to tumor spread, localization, and lesion size. Accurate assessment of these features is critical for prognosis and treatment planning. These data can be evaluated by Peritoneal Cancer Index (PCI), a quantitative index suggested by Harman and Sugarbaker. Additionally, precise predictive biomarkers should be established to predict PC in patients at risk. The radiomics analysis could predict PC throughout the evaluation of cancers heterogeneity.
Subject(s)
Hyperthermia, Induced , Peritoneal Neoplasms , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Cytoreduction Surgical Procedures , Humans , Hyperthermia, Induced/methods , Hyperthermic Intraperitoneal Chemotherapy , Peritoneal Neoplasms/diagnostic imaging , Peritoneal Neoplasms/therapyABSTRACT
OBJECTIVE: The rare hepatic tumor can have a wide spectrum of radiologic features, representing a diagnostic challenge. Our purpose is to report the experience of a National Cancer Center, emphasizing the radiological features encountered and assessing the LR-M categories in the diagnostic performances for these lesions. PATIENTS AND METHODS: We assessed 113 patients who underwent surgical resection or biopsy for rare liver lesions from May 2010 to December 2020. For these patients a computerized search of radiological records was performed to identify which had been studied with MRI and CT. For each lesion, the radiologists recorded the attenuation on CT studies and signal intensity (SI) in T1 weighted (W), in T2-W, DWI and in the related map of the apparent diffusion coefficient (ADC). We assessed the presence and the type of contrast enhancement (CE) during contrast study on CT and MRI and the enhancement was categorized according to LI-RADS 2018. We also assessed the presence of other features in LR-M categories (ancillary LR-M features) in order to classify different subgroups. The lesions were classified according to LR categories, and the gold standard was histological analysis. RESULTS: The final study population included 95 patients (46 females and 49 males), with a mean age of 51 years (range 38-83 years). 83 patients had solid lesions, 12 patients had cystic lesions (simple or complex). According to histological analysis, we categorized 79 patients with malignant lesions and 16 patients with benign lesions. According to radiological features we assessed as malignant 82 patients (79 true malignant and 3 false malignant), as benign 13 patients (all true benign). Therefore, sensitivity, specificity, positive predictive value, negative predictive value and accuracy of radiological features to identify benign and malignant lesions were 100.0%, 81.3%, 96.3%, 100.0% and 96.8%, respectively. We found no significant difference in signal and contrast enhancement appearance among all LR-M categories (p-value =0.34 at Chi square test). However, among LR-M categories the presence of satellite nodules was a feature typical of cHCC-CC (p-value < 0.05 at Chi square test). The presence of intra lesion necrosis and haemorrhage was suggestive of sarcoma (p-value < 0.05 at Chi square test). CONCLUSIONS: High diagnostic accuracy was obtained by LI-RADS classification between malignant and benign lesion. The presence of ancillary features could help the radiologist towards a correct diagnosis.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/pathology , Contrast Media , Female , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Magnetic Resonance Imaging , Male , Middle Aged , Retrospective Studies , Sensitivity and SpecificityABSTRACT
PURPOSE: COVID-19 disease may result in a severe multisystem inflammatory syndrome in children (MIS-C), which in turn may alter thyroid function (TF). We assessed TF in MIS-C, evaluating its impact on disease severity. METHODS: We retrospectively considered children admitted with MIS-C to a single pediatric hospital in Milan (November 2019-January 2021). Non-thyroidal illness syndrome (NTIS) was defined as any abnormality in TF tests (FT3, FT4, TSH) in the presence of critical illness and absence of a pre-existing hormonal abnormality. We devised a disease severity score by combining severity scores for each organ involved. Glucose and lipid profiles were also considered. A principal component analysis (PCA) was performed, to characterize the mutual association patterns between TF and disease severity. RESULTS: Of 26 (19 M/7F) patients, median age 10.7 (IQR 5.8-13.3) years, 23 (88.4%) presented with NTIS. A low FT3 level was noted in 15/23 (65.3%), while the other subjects had varying combinations of hormone abnormalities (8/23, 34.7%). Mutually correlated variables related to organ damage and inflammation were represented in the first dimension (PC1) of the PCA. FT3, FT4 and total cholesterol were positively correlated and characterized the second axis (PC2). The third axis (PC3) was characterized by the association of triglycerides, TyG index and HDL cholesterol. TF appeared to be related to lipemic and peripheral insulin resistance profiles. A possible association between catabolic components and severity score was also noted. CONCLUSIONS: A low FT3 level is common among MIS-C. TF may be useful to define the impact of MIS-C on children's health and help delineate long term follow-up management and prognosis.
Subject(s)
COVID-19/complications , Euthyroid Sick Syndromes/epidemiology , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/virology , Adolescent , COVID-19/epidemiology , COVID-19/physiopathology , COVID-19/therapy , COVID-19/virology , Child , Child, Preschool , Euthyroid Sick Syndromes/physiopathology , Euthyroid Sick Syndromes/virology , Female , Humans , Italy/epidemiology , Male , Prognosis , Retrospective Studies , SARS-CoV-2/physiology , Severity of Illness Index , Systemic Inflammatory Response Syndrome/epidemiology , Thyroid Gland/physiopathology , Thyroid Gland/virology , Thyrotropin/blood , Thyroxine , TriiodothyronineABSTRACT
This paper represents the first result of an active collaboration between the University of Sannio and the San Pio Hospital (Benevento, Italy), started in the 2018, that aims to a detailed mineralogical investigation of urinary stones of patients from Campania region. Herein, selected human bladder stones have been deeply characterized for clinical purposes and environmental biomonitoring, focusing on the importance to evaluate the concentration and distribution of undesired trace elements by means of microscopic techniques in the place of conventional wet chemical analyses. A rare bladder stone with a sea-urchin appearance, known as jackstone calculus, were also investigated (along with bladder stones made of uric acid and brushite) by means a comprehensive analytical approach, including Synchrotron X-ray Diffraction and Simultaneous Thermal Analyses. Main clinical assumptions were inferred according to the morpho-constitutional classification of bladder stones and information about patient's medical history and lifestyle. In most of the analyzed uroliths, undesired trace elements such as copper, cadmium, lead, chromium, mercury and arsenic have been detected and generally attributable to environmental pollution or contaminated food. Simultaneous occurrence of selenium and mercury should denote a methylmercury detoxification process, probably leading to the formation of a very rare HgSe compound known as tiemannite.
Subject(s)
Arsenic , Mercury , Methylmercury Compounds , Selenium , Trace Elements , Urinary Bladder Calculi , Urinary Calculi , Cadmium , Chromium , Copper , Humans , Uric Acid/analysis , Urinary Calculi/chemistry , Urinary Calculi/epidemiologyABSTRACT
BACKGROUND: Limited evidence exists to guide the management of patients with liver metastases from squamous cell carcinoma (SCC). The aim of this retrospective multicentre cohort study was to describe patterns of disease recurrence after liver resection/ablation for SCC liver metastases and factors associated with recurrence-free survival (RFS) and overall survival (OS). METHOD: Members of the European-African Hepato-Pancreato-Biliary Association were invited to include all consecutive patients undergoing liver resection/ablation for SCC liver metastases between 2002 and 2019. Patient, tumour and perioperative characteristics were analysed with regard to RFS and OS. RESULTS: Among the 102 patients included from 24 European centres, 56 patients had anal cancer, and 46 patients had SCC from other origin. RFS in patients with anal cancer and non-anal cancer was 16 and 9 months, respectively (P = 0.134). A positive resection margin significantly influenced RFS for both anal cancer and non-anal cancer liver metastases (hazard ratio 6.82, 95 per cent c.i. 2.40 to 19.35, for the entire cohort). Median survival duration and 5-year OS rate among patients with anal cancer and non-anal cancer were 50 months and 45 per cent and 21 months and 25 per cent, respectively. For the entire cohort, only non-radical resection was associated with worse overall survival (hazard ratio 3.21, 95 per cent c.i. 1.24 to 8.30). CONCLUSION: Liver resection/ablation of liver metastases from SCC can result in long-term survival. Survival was superior in treated patients with liver metastases from anal versus non-anal cancer. A negative resection margin is paramount for acceptable outcome.
Subject(s)
Carcinoma, Squamous Cell , Liver Neoplasms , Carcinoma, Squamous Cell/surgery , Cohort Studies , Humans , Liver Neoplasms/surgery , Neoplasm Recurrence, Local/surgery , Retrospective StudiesABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) represents a challenge for a multidisciplinary oncology team. Diagnosis of PDAC remains challenging due to overlapping imaging features with benign lesions, notwithstanding great advances with computed tomography (CT) and magnetic resonance imaging (MRI). The term "Radiomics" has recently been introduced to define a mathematical process to extract countless quantitative features from medical images (including each diagnostic technique) with high throughput computing for diagnosis and prediction. This article is an updated overview of the imaging techniques to be employed during detection and characterization of pancreatic cancer diagnostic workup. Particularly, the limitations and advantages of the different imaging techniques are discussed, with a particular focus on functional imaging. This overview is the result of a self-study without protocol and registration number. Articles published in the English language from January 2000 to January 2021 were included. We analyzed 15 papers on radiomics. The possibility of functional imaging, such as CT, MRI, and radiomics has revolutionized pancreatic imaging, improving the detection and characterization of the lesions and allowing a prognosis related to radiological features, favoring the process of personalized medicine.
Subject(s)
Pancreatic Neoplasms/diagnostic imaging , Humans , Magnetic Resonance Imaging , Pancreas/diagnostic imaging , Tomography, X-Ray ComputedABSTRACT
Electroporation (EP) techniques, used alone (Irreversible Electroporation, IRE) or in combination with anti-cancer drugs (Electrochemotherapy, ECT), have been shown to be effective in the treatment of several types of cancers. The efficacy of ECT and IRE is well demonstrated for the treatment of non-superficial tumor metastases, and it depends on the applied electrical parameters. Particularly, ECT is an effective local therapy that uses electroporation to enhance the cytotoxic effect of bleomycin or cisplatin injected intravenously or intratumorally. Pre-clinical investigations to test alternative anti-cancer drugs, explore new combinations of treatment modalities, and evaluate different sets of pulse protocols for effective tissue electroporation, are ongoing. Further ECT developments include the treatment of deep-seated tumors with percutaneous, laparoscopy, and endoscopy approaches, with the aim of establishing a less invasive approach. ECT is highly effective in the treatment of tumors of any histology, in minimizing the damage of critical normal tissue or organs, and in reducing pain and muscular contractions. This work describes the new technological advances in the field of ECT treatment for deep-seated tumors.
Subject(s)
Antineoplastic Agents/therapeutic use , Bleomycin/therapeutic use , Cisplatin/therapeutic use , Neoplasms/drug therapy , Administration, Intravenous , Antineoplastic Agents/administration & dosage , Bleomycin/administration & dosage , Cisplatin/administration & dosage , Electrochemotherapy , Electrodes , Electroporation , Humans , LaparoscopyABSTRACT
The assessment of tumor response, after neoadjuvant radiochemotherapy (nCRT), allows stratifying the patient in order to consider the proper therapeutical management. Histopathology analysis of the surgical specimen is considered the gold standard to assess tumour response and the definition of a complete cancer response is related to the clinical and endoscopic features, by direct evaluation of the rectal wall. However, imaging studies, especially Magnetic Resonance Imaging (MRI) have provided additional parameters, as the evaluation of nodal or mesorectal status. MRI provides a radiological tumour regression grade (mrTRG) that is correlated with the pathologic tumor regression grade (pTRG). Functional MRI parameters have additional impending in early prediction of the efficacy of therapy and can be valuable in drug development processes. Some of functional methodologies are already part of clinical practice: diffusion-weighted MRI (DW-MRI) and perfusion imaging (dynamic contrast enhanced MRI [DCE-MRI]). Other technologies, such as radiomics with MRI are still in the experimental phase. An adequate radiological report describing the restaging of rectal cancer after nCRT should be a "structured report" to improve communication in a multidisciplinary team.
Subject(s)
Chemoradiotherapy, Adjuvant , Neoplasm Recurrence, Local/therapy , Rectal Neoplasms/therapy , Humans , Magnetic Resonance Imaging , Neoplasm Recurrence, Local/diagnostic imaging , Radiologists , Rectal Neoplasms/diagnostic imagingABSTRACT
OBJECTIVE: To describe the role of the Diffusion Weighted Imaging (DWI) in the assessment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Several electronic databases were evaluated in the present review. The search included articles published from January 2010 to May 2019. The references of all articles were also evaluated. All titles and abstracts were assessed, and only the studies of DWI in patients with HCC were retained. RESULTS: HCC is the most common primitive hepatic cancer. The non-invasive radiological criteria for HCC diagnosis are based on the presence of the specific vascular profile characterized by contrast uptake during arterial phase, defined as arterial hyperenhancement, followed by washout in the venous/portal phase. However, arterial hyperenhancement and wash out appearance have a sensitivity rate of 50-60% in lesion smaller than 2 cm. Therefore, other functional parameters have been introduced in the detection and characterization of HCC nodules. DWI has been applied to liver imaging as an excellent tool for detection and characterization of focal liver lesions, increasing clinical confidence and decreasing false positives. The assessment of DW images can be done qualitatively and quantitatively, through the apparent diffusion coefficient (ADC) map. Intravoxel incoherent motion (IVIM) is a more sophisticated analysis, a biexponential model, to better defining the relationship between signal attenuation and increasing b value that separately reproduces tissue diffusivity and tissue perfusion. Traditionally DWI approach to analyze data is founded on the hypothesis that water molecules diffuse within a voxel following a single direction with a Gaussian behavior without any restriction. However, according to the presence of microstructures, water molecules within biologic tissues exhibits a non-Gaussian phenomena proposed by Jensen in 2005 called Diffusion Kurtosis Imaging (DKI). This approach assesses the kurtosis coefficient (K) that shows the deviance of diffusion from a Gaussian approach, and the diffusion coefficient (D) with the correction of non-Gaussian bias. DKI is an advanced DWI model that quantifies non-Gaussian behavior of diffusion and provides both a corrected ADC, as well as the excess kurtosis of tissue, a measure of the extent to which tissue diffusion deviates from a Gaussian pattern. It is believed that the DKI model is more sensitive to tissue microstructural complexity than standard DW. CONCLUSIONS: DWI should be an integral part of study protocol for HCC patients, considering the great advantages due to DWI and DWI-based approaches in detection and characterization of HCC.
Subject(s)
Carcinoma, Hepatocellular/diagnostic imaging , Diffusion Magnetic Resonance Imaging , Liver Neoplasms/diagnostic imaging , Artifacts , Carcinoma, Hepatocellular/pathology , Humans , Liver Neoplasms/pathology , Predictive Value of Tests , Reproducibility of ResultsABSTRACT
OBJECTIVE: Cholangiocarcinoma (CCA) is the second most common primary hepatic malignancy after hepatocellular carcinoma. The current standard palliative treatment, chemotherapy regimen with gemcitabine and cisplatin, prolongs overall survival only of a few months. Established locoregional therapies are not a curative option or an alternative to surgery in the treatment of CCA. We report a case of a patient affected by a cholangiocellular carcinoma at hepatic hilum treated by Electrochemotherapy (ECT) at our oncologic center. CASE PRESENTATION: A 71 years old male affected by a CCA at hepatic hilum was treated with ECT according to ESOPE guidelines. No complications occurred during ECT procedure. The patient was discharged after 10 days. The functional MR evaluation at 2 and at 4 months post-treatment showed a significant response without significant post-treatment adverse events. The Computed tomography (CT) assessment after 18 months did not show progression of disease. CONCLUSIONS: ECT is safe and its use could be suggested as a palliative treatment of advanced neoplastic lesions in which radical surgical treatment is not possible.
Subject(s)
Antineoplastic Agents/pharmacology , Bile Duct Neoplasms/drug therapy , Bile Ducts, Intrahepatic/drug effects , Cholangiocarcinoma/drug therapy , Cisplatin/pharmacology , Deoxycytidine/analogs & derivatives , Electrochemotherapy , Aged , Bile Duct Neoplasms/diagnostic imaging , Bile Ducts, Intrahepatic/pathology , Cholangiocarcinoma/diagnostic imaging , Deoxycytidine/pharmacology , Humans , Male , Tomography, X-Ray Computed , GemcitabineABSTRACT
There are a number of chemotherapy-effects that should be assessed with liver imaging since they have an influence on surgical morbidity. Chemotherapy-related complications, steatosis, chemotherapy-associated steatohepatitis (CASH), and SOS might impair the hepatic parenchyma, thus reducing the functionality and inï¬uencing the outcome following resection. The main role of a radiologist is to provide an accurate diagnosis of the lesion. With constant advances in medicine, a radiologist's role should extend beyond just reporting the data of tumor, providing additional information that may greatly improve patient care. Radiologists should assess both chemotherapy effects on the hepatic metastasis itself, as well as chemo-induced focal and diffuse modifications of non-tumor hepatic parenchyma, since it is important to avoid impaired hepatic function after hepatic resection.
Subject(s)
Antineoplastic Agents/adverse effects , Colorectal Neoplasms/diagnosis , Liver Neoplasms/diagnosis , Liver Neoplasms/secondary , Antineoplastic Agents/therapeutic use , Colorectal Neoplasms/drug therapy , Humans , Liver Neoplasms/drug therapyABSTRACT
We present a multi-analytical in situ non-invasive study of a series of emblematic paintings by Alessandro Milesi (1856-1945) from the collection of the International Gallery of Modern Art Ca' Pesaro in Venice. Eight paintings dated from 1897 to 1910 were studied with imaging and spectroscopic techniques. White pigments were characterized by a combination of X-ray fluorescence spectroscopy which traced the presence of zinc-based pigments in Milesi's paintings, Raman Spectroscopy, Laser Induced Fluorescence (LIF) Spectroscopy and Time-resolved Luminescence Imaging. Time-resolved analysis of luminescence emissions revealed the nanosecond emission from organic compounds and the slower emission from the luminescent inorganic pigment Zinc Oxide that varied between 1.1 and 1.6 microseconds. In this work, data regarding the distribution of luminescent pigments was acquired with a time-gated imaging detector. Furthermore, differences in emission decay kinetics recorded from different paintings can be ascribed to different paint formulations or origins of the Zinc white in paint.
ABSTRACT
A complementary multi-analytical in-situ approach has been adopted for the investigation of a corpus of ten paintings dating from 1889 and 1940 by the Venetian painter Alessandro Milesi (1856-1945), from the collection of the International Gallery of Modern Art Ca' Pesaro in Venice. Analyses were performed in situ with digital imaging, elemental and spectroscopic analysis. The analysis of pigments and binding media and their possible deterioration patterns were studied with a combination of X-Ray Fluorescence (XRF) Spectroscopy, External Reflection- Fourier Transform Infrared Spectroscopy (ER-FTIR) and Raman Spectroscopy. These analytical methods provide information regarding the evolution of the artist's palette and the painting techniques adopted in painting. Data suggest the widespread detection of zinc carboxylates, with implications for conservation and display.
ABSTRACT
Background: Arginine depletion is a putative target in hepatocellular carcinoma (HCC). HCC often lacks argininosuccinate synthetase, a citrulline to arginine-repleting enzyme. ADI-PEG 20 is a cloned arginine degrading enzyme-arginine deiminase-conjugated with polyethylene glycol. The goal of this study was to evaluate this agent as a potential novel therapeutic for HCC after first line systemic therapy. Methods and patients: Patients with histologically proven advanced HCC and Child-Pugh up to B7 with prior systemic therapy, were randomized 2 : 1 to ADI-PEG 20 18 mg/m2 versus placebo intramuscular injection weekly. The primary end point was overall survival (OS), with 93% power to detect a 4-5.6 months increase in median OS (one-sided α = 0.025). Secondary end points included progression-free survival, safety, and arginine correlatives. Results: A total of 635 patients were enrolled: median age 61, 82% male, 60% Asian, 52% hepatitis B, 26% hepatitis C, 76% stage IV, 91% Child-Pugh A, 70% progressed on sorafenib and 16% were intolerant. Median OS was 7.8 months for ADI-PEG 20 versus 7.4 for placebo (P = 0.88, HR = 1.02) and median progression-free survival 2.6 months versus 2.6 (P = 0.07, HR = 1.17). Grade 3 fatigue and decreased appetite occurred in <5% of patients. Two patients on ADI-PEG 20 had ≥grade 3 anaphylactic reaction. Death rate within 30 days of end of treatment was 15.2% on ADI-PEG 20 versus 10.4% on placebo, none related to therapy. Post hoc analyses of arginine assessment at 4, 8, 12 and 16 weeks, demonstrated a trend of improved OS for those with more prolonged arginine depletion. Conclusion: ADI-PEG 20 monotherapy did not demonstrate an OS benefit in second line setting for HCC. It was well tolerated. Strategies to enhance prolonged arginine depletion and synergize the effect of ADI-PEG 20 are underway. Clinical Trial number: www.clinicaltrials.gov (NCT 01287585).
Subject(s)
Carcinoma, Hepatocellular/therapy , Hydrolases/therapeutic use , Liver Neoplasms/therapy , Palliative Care , Polyethylene Glycols/therapeutic use , Carcinoma, Hepatocellular/pathology , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Liver Neoplasms/pathology , Male , Middle Aged , Prognosis , Survival RateABSTRACT
OBJECTIVE: Refractory ascites is defined as a lack of response to high doses of diuretics or the development of diuretic related side effects, which compel the patient to discontinue the diuretic treatment. Current therapeutic strategies include repeated large-volume paracentesis and transjugular intrahepatic portosystemic shunts (TIPS). Peritoneovenous shunt (Denver shunt) should be considered for patients with refractory ascites who are not candidates for paracentesis or TIPS. This study presents our case series in the implant of Denver peritoneovenous shunt. PATIENTS AND METHODS: Sixty-two patients underwent percutaneous placement of Denver shunt between November 2003 and July 2014. There were 36 men and 26 women. Ascites was secondary to alcoholic cirrhosis in six patients, cryptogenic cirrhosis in six, and virus-related cirrhosis in fifty of them. Liver cirrhosis was classified as Child B in 22 patients and Child C in 40 (no patient was Child A). RESULTS: All implants were successfully performed. There were no intraoperative problems or lethal complications; our patients were hospitalized for 2 or 3 days. Postoperative complications included: infection of the shunt in 3 patients (4.8%), shunt obstruction in 4 (6.4%) and transient abdominal pain in 4 (6.4%). Significant symptomatic relief was obtained in all patients. CONCLUSIONS: The percutaneous placement of a Denver shunt is a technically feasible and effective method for symptomatic relief of refractory ascites.