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3. Inflammatory Gene Expression Associates with Hepatitis B Virus cccDNA- but Not Integrant-Derived Transcripts in HBeAg Negative Disease

Author

Magri, Andrea, primary, Harris, James M., additional, D’Arienzo, Valentina, additional, Minisini, Rosalba, additional, Jühling, Frank, additional, Wing, Peter A. C., additional, Rapetti, Rachele, additional, Leutner, Monica, additional, Testoni, Barbara, additional, Baumert, Thomas F., additional, Zoulim, Fabien, additional, Balfe, Peter, additional, Pirisi, Mario, additional, and McKeating, Jane A., additional

Published
2022
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7. Accuracy of Transient Elastography in assessing fibrosis at diagnosis in naïve patients with Primary Biliary Cholangitis: a dual cut-off approach

Author

Cristoferi, L, Calvaruso, V, Overi, D, Viganò, M, Rigamonti, C, Degasperi, E, Cardinale, V, Labanca, S, Zucchini, N, Fichera, A, Di Marco, V, Leutner, M, Venere, R, Picciotto, A, Lucà, M, Mulinacci, G, Palermo, A, Gerussi, A, D'Amato, D, O'Donnell, S, Cerini, F, De Benedittis, C, Malinverno, F, Ronca, V, Mancuso, C, Cazzagon, N, Ciaccio, A, Barisani, D, Marzioni, M, Floreani, A, Alvaro, D, Gaudio, E, Invernizzi, P, Carpino, G, Nardi, A, Carbone, M, Cristoferi, Laura, Calvaruso, Vincenza, Overi, Diletta, Viganò, Mauro, Rigamonti, Cristina, Degasperi, Elisabetta, Cardinale, Vincenzo, Labanca, Sara, Zucchini, Nicola, Fichera, Anna, Di Marco, Vito, Leutner, Monica, Venere, Rosanna, Picciotto, Antonino, Lucà, Martina, Mulinacci, Giacomo, Palermo, Andrea, Gerussi, Alessio, D'Amato, Daphne, O'Donnell, Sarah Elisabeth, Cerini, Federica, De Benedittis, Carla, Malinverno, Federica, Ronca, Vincenzo, Mancuso, Clara, Cazzagon, Nora, Ciaccio, Antonio, Barisani, Donatella, Marzioni, Marco, Floreani, Annarosa, Alvaro, Domenico, Gaudio, Eugenio, Invernizzi, Pietro, Carpino, Guido, Nardi, Alessandra, Carbone, Marco, Cristoferi, L, Calvaruso, V, Overi, D, Viganò, M, Rigamonti, C, Degasperi, E, Cardinale, V, Labanca, S, Zucchini, N, Fichera, A, Di Marco, V, Leutner, M, Venere, R, Picciotto, A, Lucà, M, Mulinacci, G, Palermo, A, Gerussi, A, D'Amato, D, O'Donnell, S, Cerini, F, De Benedittis, C, Malinverno, F, Ronca, V, Mancuso, C, Cazzagon, N, Ciaccio, A, Barisani, D, Marzioni, M, Floreani, A, Alvaro, D, Gaudio, E, Invernizzi, P, Carpino, G, Nardi, A, Carbone, M, Cristoferi, Laura, Calvaruso, Vincenza, Overi, Diletta, Viganò, Mauro, Rigamonti, Cristina, Degasperi, Elisabetta, Cardinale, Vincenzo, Labanca, Sara, Zucchini, Nicola, Fichera, Anna, Di Marco, Vito, Leutner, Monica, Venere, Rosanna, Picciotto, Antonino, Lucà, Martina, Mulinacci, Giacomo, Palermo, Andrea, Gerussi, Alessio, D'Amato, Daphne, O'Donnell, Sarah Elisabeth, Cerini, Federica, De Benedittis, Carla, Malinverno, Federica, Ronca, Vincenzo, Mancuso, Clara, Cazzagon, Nora, Ciaccio, Antonio, Barisani, Donatella, Marzioni, Marco, Floreani, Annarosa, Alvaro, Domenico, Gaudio, Eugenio, Invernizzi, Pietro, Carpino, Guido, Nardi, Alessandra, and Carbone, Marco

Abstract

Background and Aims: Liver fibrosis holds a relevant prognostic meaning in primary biliary cholangitis (PBC). Noninvasive fibrosis evaluation using vibration-controlled transient elastography (VCTE) is routinely performed. However, there is limited evidence on its accuracy at diagnosis in PBC. We aimed to estimate the diagnostic accuracy of VCTE in assessing advanced fibrosis (AF) at disease presentation in PBC. Approach and Results: We collected data from 167 consecutive treatment-naïve PBC patients who underwent liver biopsy (LB) at diagnosis at six Italian centers. VCTE examinations were completed within 12 weeks of LB. Biopsies were scored by two blinded expert pathologists, according to the Ludwig system. Diagnostic accuracy was estimated using the area under the receiver operating characteristic curves (AUROCs) for AF (Ludwig stage ≥III). Effects of biochemical and clinical parameters on liver stiffness measurement (LSM) were appraised. The derivation cohort consisted of 126 patients with valid LSM and LB; VCTE identified patients with AF with an AUROC of 0.89. LSM cutoffs ≤6.5 and >11.0 kPa enabled to exclude and confirm, respectively, AF (negative predictive value [NPV] = 0.94; positive predictive value [PPV] = 0.89; error rate = 5.6%). These values were externally validated in an independent cohort of 91 PBC patients (NPV = 0.93; PPV = 0.89; error rate = 8.6%). Multivariable analysis found that the only parameter affecting LSM was fibrosis stage. No association was found with BMI and liver biochemistry. Conclusions: In a multicenter study of treatment-naïve PBC patients, we identified two cutoffs (LSM ≤6.5 and >11.0 kPa) able to discriminate at diagnosis the absence or presence, respectively, of AF in PBC patients, with external validation. In patients with LSM between these two cutoffs, VCTE is not reliable and liver biopsy should be evaluated for accurate disease staging. BMI and liver biochemistry did not affect LSMs.

Published
2021

9. Accuracy of liver stiffness measurement in assessing liver fibrosis in naive patients with primary biliary cholangitis

Author

Cristoferi, Laura, primary, Nardi, Alessandra, additional, Viganò, Mauro, additional, Rigamonti, Cristina, additional, Degasperi, Elisabetta, additional, Cardinale, Vincenzo, additional, Labanca, Sara, additional, Zucchini, Nicola, additional, Leutner, Monica, additional, Venere, Rosanna, additional, Picciotto, Antonino, additional, Cazzagon, Nora, additional, Lucà, Martina, additional, Overi, Diletta, additional, Gerussi, Alessio, additional, D’Amato, Daphne, additional, O’Donnell, Sarah Elisabeth, additional, Cerini, Federica, additional, De Benedittis, Carla, additional, Cadamuro, Massimiliano, additional, Malinverno, Federica, additional, Floreani, Annarosa, additional, Alvaro, Domenico, additional, Gaudio, Eugenio, additional, Invernizzi, Pietro, additional, Carpino, Guido, additional, and Carbone, Marco, additional

Published
2020
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13. Accuracy of liver stiffness measurement in assessing liver fibrosis in naive patients with primary biliary cholangitis

Author

LAURA CRISTOFERI, Nardi, Alessandra, Vigano, Mauro, Rigamonti, Cristina, Degasperi, Elisabetta, Cardinale, Vincenzo, Labanca, Sara, Zucchini, Nicola, Leutner, Monica, Venere, Rosanna, Picciotto, Antonino, Cazzagon, Nora, Luca, Martina, Overi, Diletta, Gerussi, Alessio, D Amato, Daphne, O Donnell, Sarah Elisabeth, Cerini, Federica, Benedittis, Carla, Cadamuro, Massimiliano, Malinverno, Federica, Floreani, Annarosa, Alvaro, Domenico, Gaudio, Eugenio, Invernizzi, Pietro, Carpino, Guido, Carbone, Marco, Cristoferi, L, Nardi, A, Viganò, M, Rigamonti, C, Degasperi, E, Cardinale, V, Labanca, S, Zucchini, N, Leutner, M, Venere, R, Picciotto, A, Cazzagon, N, Lucà, M, Overi, D, Gerussi, A, D’Amato, D, O’Donnell, S, Cerini, F, De Benedittis, C, Cadamuro, M, Malinverno, F, Floreani, A, Alvaro, D, Gaudio, E, Invernizzi, P, Carpino, G, and Carbone, M

Subjects
Hepatology, Primary biliary cholangiti, Fibrosi, Autoimmune liver disease, Vibration-Controlled Transient Elastography, Risk stratification
Abstract

Background and Aims: Non-invasive evaluation of liver fibrosis in primary biliary cholangitis (PBC) with Liver Stiffness Measurements (LSM) by Transient Elastography (TE) is routinely undertaken at diagnosis for disease staging and risk stratification. However, evidence on correlation between LSM and liver fibrosis is based on cross-sectional studies in PBC-treated patients. Moreover, the impact of potential confounders, e.g. cholestasis and steatosis, is unclear. Aim of our study was to investigate the accuracy of LSM to predict moderate to severe fibrosis in newly diagnosed PBC patients naïve to therapy. Method: We collected data from 182 adult patients who underwent liver biopsy (LB) for PBC at diagnosis in five Italian liver centers from Jan 2006 through Aug 2019. TE examinations within 3 months from LB were included. LB were scored centrally by two expert pathologists, blinded to clinical data and disease stage, according to Ludwig staging system. In all patients Fibrosis-4 (FIB-4) and aspartate aminotransferase [AST]/platelet ratio (APRI) score have been calculated. Diagnostic accuracy of LSM, FIB-4 and APRI score was estimated using the area under the receiver operating characteristic curves (AUROCs) for fibrosis. The effects of liver biochemistry and histological parameters were appraised using multivariable logistic model. Results: 123 PBC patients had adequate LB (≥9 portal tracts) and valid LSM values. According to histological assessment, Ludwig stage distribution was as follows: stage I = 38 (30.9%), stage II = 46(37.4%), stage III = 27 (21.9%), stage IV = 12 (9.8%). TE identified patients with Ludwig stage III/IV with an AUROC of 0.83 (95% confidence interval [CI] (0.74, 0.90)) (Fig.1). The optimal threshold was identified at 6.75kPa (CI (6.55, 7.50)), with 85% of sensitivity, 75% of specificity, 78% of accuracy and 6 false negative. TE was superior to APRI and FIB-4 having AUROC of 0.638 (CI = (0.535, 0.740)) and 0.641 (CI = (0.516, 0.766)), respectively. At multivariable analysis only LSM was associated with liver fibrosis and no significant effect of biochemical measures and steatosis was found. Conclusion: LSM is accurate to predict moderate to severe liver fibrosis at diagnosis in PBC naïve patients using a threshold of 6.75kPa with an AUROC of 0.83. TE outperformed FIB-4 and APRI score and is not confounded by liver biochemistry and steatosis. These data can inform strategies for patient surveillance and trial design in PBC.

Published
2020

16. Identification of mutations in circulating cell-free tumour DNA as a biomarker in hepatocellular carcinoma

Author

Howell, Jessica, Atkinson, Stephen R., Pinato, David J., Knapp, Susanne, Ward, Caroline, Minisini, Rosalba, Burlone, Michela E., Leutner, Monica, Pirisi, Mario, Buettner, Reinhard, Khan, Shahid A., Thursz, Mark, Odenthal, Margarete, Sharma, Rohini, Howell, Jessica, Atkinson, Stephen R., Pinato, David J., Knapp, Susanne, Ward, Caroline, Minisini, Rosalba, Burlone, Michela E., Leutner, Monica, Pirisi, Mario, Buettner, Reinhard, Khan, Shahid A., Thursz, Mark, Odenthal, Margarete, and Sharma, Rohini

Abstract

Background: Hepatocellular carcinoma (HCC) is increasing globally. Prognostic biomarkers are urgently needed to guide treatment and reduce mortality. Tumour-derived circulating cell-free DNA (ctDNA) is a novel, minimally invasive means of determining genetic alterations in cancer. We evaluate the accuracy of ctDNA as a biomarker in HCC. Methods: Plasma cell-free DNA, matched germline DNA and HCC tissue DNA were isolated from patients with HCC (n = 51) and liver cirrhosis (n = 10). Targeted, multiplex polymerase chain reaction ultra-deep sequencing was performed using a liver cancer-specific primer panel for genes ARID1A, ARID2, AXIN1, ATM, CTNNB1, HNF1A and TP53. Concordance of mutations in plasma ctDNA and HCC tissue DNA was determined, and associations with clinical outcomes were analysed. Results: Plasma cell-free DNA was detected in all samples. Lower plasma cell-free DNA levels were seen in Barcelona Clinic Liver Cancer (BCLC A compared with BCLC stage B/C/D (median concentration 122.89 ng/mL versus 168.21 ng/mL, p = 0.041). 29 mutations in the eight genes (21 unique mutations) were detected in 18/51 patients (35%), median 1.5 mutations per patient (interquartile range 1-2). Mutations were most frequently detected in ARID1A (11.7%), followed by CTNNB1 (7.8%) and TP53 (7.8%). In patients with matched tissue DNA, all mutations detected in plasma ctDNA detected were confirmed in HCC DNA; however, 71% of patients had mutations identified in HCC tissue DNA that were not detected in matched ctDNA. Conclusion: ctDNA is quantifiable across all HCC stages and allows detection of mutations in key driver genes of hepatic carcinogenesis. This study demonstrates high specificity but low sensitivity of plasma ctDNA for detecting mutations in matched HCC tissue. Crown Copyright (C) 2019 Published by Elsevier Ltd. All rights reserved.

Published
2019

17. FRI-011-Ductular reaction, intermediate hepatocites and fibrosis extension correlate with prediction of treatment failure to ursodeoxycholic acid in primary biliary cholangitis

Author

Cristoferi, L, Carpino, G, Cardinale, V, Rigamonti, C, Overi, D, Zucchini, N, Leutner, M, Viganò, M, Nardi, A, Gerussi, A, Ronca, V, Cadamuro, M, Bonato, G, Alvaro, D, Gaudio, E, Jones, D, Invernizzi, P, Mells, G, Carbone, M, Cristoferi, Laura, Carpino, Guido, Cardinale, Vincenzo, Rigamonti, Cristina, Overi, Diletta, Zucchini, Nicola, Leutner, Monica, Viganò, Mauro, Nardi, Alessandra, Gerussi, Alessio, Ronca, Vincenzo, Cadamuro, Massimiliano, Bonato, Giulia, Alvaro, Domenico, Gaudio, Eugenio, Jones, David, Invernizzi, Pietro, Mells, George, Carbone, Marco, Cristoferi, L, Carpino, G, Cardinale, V, Rigamonti, C, Overi, D, Zucchini, N, Leutner, M, Viganò, M, Nardi, A, Gerussi, A, Ronca, V, Cadamuro, M, Bonato, G, Alvaro, D, Gaudio, E, Jones, D, Invernizzi, P, Mells, G, Carbone, M, Cristoferi, Laura, Carpino, Guido, Cardinale, Vincenzo, Rigamonti, Cristina, Overi, Diletta, Zucchini, Nicola, Leutner, Monica, Viganò, Mauro, Nardi, Alessandra, Gerussi, Alessio, Ronca, Vincenzo, Cadamuro, Massimiliano, Bonato, Giulia, Alvaro, Domenico, Gaudio, Eugenio, Jones, David, Invernizzi, Pietro, Mells, George, and Carbone, Marco

Published
2019

18. Accuracy of Transient Elastography in Assessing Fibrosis at Diagnosis in Naïve Patients With Primary Biliary Cholangitis: A Dual Cut‐Off Approach.

Author

Cristoferi, Laura, Calvaruso, Vincenza, Overi, Diletta, Viganò, Mauro, Rigamonti, Cristina, Degasperi, Elisabetta, Cardinale, Vincenzo, Labanca, Sara, Zucchini, Nicola, Fichera, Anna, Di Marco, Vito, Leutner, Monica, Venere, Rosanna, Picciotto, Antonino, Lucà, Martina, Mulinacci, Giacomo, Palermo, Andrea, Gerussi, Alessio, D'Amato, Daphne, and Elisabeth O'Donnell, Sarah

Published
2021
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21. Identification of mutations in circulating cell-free tumour DNA as a biomarker in hepatocellular carcinoma

Author

Howell, Jessica, primary, Atkinson, Stephen R., additional, Pinato, David J., additional, Knapp, Susanne, additional, Ward, Caroline, additional, Minisini, Rosalba, additional, Burlone, Michela E., additional, Leutner, Monica, additional, Pirisi, Mario, additional, Büttner, Reinhard, additional, Khan, Shahid A., additional, Thursz, Mark, additional, Odenthal, Margarete, additional, and Sharma, Rohini, additional

Published
2019
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23. FRI-011-Ductular reaction, intermediate hepatocites and fibrosis extension correlate with prediction of treatment failure to ursodeoxycholic acid in primary biliary cholangitis

Author

Cristoferi, Laura, primary, Carpino, Guido, additional, Cardinale, Vincenzo, additional, Rigamonti, Cristina, additional, Overi, Diletta, additional, Zucchini, Nicola, additional, Leutner, Monica, additional, Viganò, Mauro, additional, Nardi, Alessandra, additional, Gerussi, Alessio, additional, Ronca, Vincenzo, additional, Cadamuro, Massimiliano, additional, Bonato, Giulia, additional, Alvaro, Domenico, additional, Gaudio, Eugenio, additional, Jones, David, additional, Invernizzi, Pietro, additional, Mells, George, additional, and Carbone, Marco, additional

Published
2019
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25. Expression of p53, gluthathione S-transferase-pi, and Bcl-2 proteins and benefit from adjuvant radiotherapy in breast cancer

Author

Silvestrini, Rosella, Veneroni, Silvia, Benini, Elvira, Daidone, Maria Grazia, Luisi, Antonella, Leutner, Monica, Maucione, Antonio, Kenda, Rado, Zucali, Roberto, and Veronesi, Umberto

Subjects
Breast cancer -- Adjuvant treatment, Radiotherapy -- Evaluation, Health
Abstract

Background: In clinical breast cancer research, the utility of certain biomarkers as predictors of response to surgery, chemotherapy, or hormonal therapy has been studied intensively. Much less research has been done on the relevance of biologic predictors of response to radiotherapy, which represents an effective local-regional treatment for breast cancer. Purpose: The utility of biomarkers involved in DNA damage repair (p53 protein), control of programmed cell death (p53 and Bcl-2 proteins), and cellular detoxification (glutathione S-transferase-[Pi] [GST-[Pi]] enzyme) in predicting local breast cancer recurrence was analyzed retrospectively in two cohorts of breast cancer patients. These patients had had no detectable metastases in the axillary lymph nodes (i.e., node-negative) or in distant sites and had had similar distributions of clinicopathologic and biologic prognostic features. They had been treated by conservative surgery alone (139 case patients) or by conservative surgery followed by adjuvant radiotherapy (496 case patients) during the period from 1984 through 1990. Methods: The expression of the p53, GST- Pi], and Bcl-2 proteins in the specimens of primary breast tumor obtained from these patients was determined by use of immunohistochemistry; cell proliferation activity and levels of steroid receptors were determined by use of a [[sup.3.H]thymidine-labeling index assay and the dextran-coated charcoal technique, respectively. The median time of follow-up of patients was 6 years. In the analyses of patient outcomes, only local failures that presented as first events were considered. Results: After surgery alone, the risk of local recurrence at 6 years was higher for patients with tumors exhibiting elevated levels of p53 and GST- [Pi], protein expression than for patients with low levels (hazard ratio [HR] = 3.1, 95% confidence interval [CI] = 1.3-7.7, two-sided P = .012; HR = 2.7, 95% CI = 1.1-6.4, two-sided P = .026, respectively). Weak or no observable expression of Bcl-2 protein was only suggestive of a higher frequency of local failures. Adjustment for patient age, tumor size, cell proliferation, and estrogen receptor status did not change these findings. Conversely, in the series of patients given conservative surgery followed by radiotherapy, there was no difference in local tumor recurrence between patients with tumors expressing or not expressing each of the three markers. Conclusions: Our study provides indirect evidence of a benefit from radiation therapy in preventing local breast cancer relapse, particularly among node-negative patients with tumors that express elevated levels of the p53 or GST- [Pi] proteins or that express little or no Bcl-2 protein. [J Natl Cancer Inst 1997;89:639-45]

Published
1997

27. Reliability and reproducibility of the Edmondson grading of hepatocellular carcinoma using paired core biopsy and surgical resection specimens

Author

Pirisi, Mario, Leutner, Monica, Pinato, David J., Avellini, Claudio, Carsana, Luca, Toniutto, Pierluigi, Fabris, Carlo, and Boldorini, Renzo

Subjects
Liver -- Transplantation, Hepatoma -- Analysis, Surgery -- Analysis, Health
Abstract

* Context.--It has been claimed that the Edmondson and Steiner grading system (EGS) values should be obtained preoperatively to select patients with hepatocellular carcinoma for liver transplantation. However, EGS reliability in biopsy specimens has been questioned. Objective.--To verify the reliability of the EGS using core biopsy specimens and its reproducibility among pathologists. Design.--Paired biopsy and surgical specimens obtained from 40 patients (subset 1) were retrieved by means of computer-aided search of the pathology records and blindly and independently reviewed. The EGS interrater agreement was measured using k statistics. After having held a consensus meeting, pathologists graded an additional 21 paired hepatocellular carcinoma specimens (subset 2). Results.--Analyzing subset 1, pathologists gave significantly lower EGS grades to the biopsy specimens (P < .001), for which the observed agreement was 32.5% (κ = 0.021), which increased to 82.5% (κ = 0.186) if only 2 categories were considered (low grade, EGS I-II; high grade, EGS III-IV). The observed agreement in the case of the surgical specimens was 52.5% (κ = 0.199), which increased to 62.5% (κ = 0.275) when the low- and highgrade scores were merged. The observed agreement between the assessments of paired biopsy and surgical specimens was 50.0% for pathologist 1 (κ = 0.057) and 35.0% for pathologist 2 (κ = 0.078). Merging the EGS grades did not improve the strength of the agreement. Analyzing subset 2 (after the consensus meeting), the observed agreement between pathologists improved more on biopsies (76.2%, κ = 0.614) than on surgical specimens (61.9%, κ = 0.434). Conclusions.--The EGS is easily underestimated in core biopsy specimens, and interrater disagreement between pathologists can be significant unless consensus meetings are held. (Arch Pathol Lab Med. 2010;134:1818-1822), It has been shown that the prognosis of hepatocellular carcinoma (HCC), the fifth most common solid tumor worldwide and the third leading cause of cancer-related death, can be predicted by [...]

Published
2010

29. Intra-tumour heterogeneity in the regulation of immune-tolerogenic pathways in primary and metastatic hepatocellular carcinoma (HCC).

Author

Pinato, David James, primary, Victor, Stephane, additional, Spina, Paolo, additional, Trivedi, Pritesh, additional, Pirisi, Mario, additional, Burlone, Michela, additional, Black, James M, additional, Minisini, Rosalba, additional, Leutner, Monica, additional, Boldorini, Renzo, additional, Mauri, Francesco A, additional, and Sharma, Rohini, additional

Published
2017
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38. Human pulmonary dirofilariasis: uncommon cause of pulmonary coin-lesion

Author

Rena, Ottavio, Leutner, Monica, and Casadio, Caterina

Subjects
*DIROFILARIA, *HEART diseases
Abstract

Pulmonary dirofilariasis is a rare entity caused by Dirofilaria, a dog worm that is transmitted to humans by mosquitoes. The filarial nematode enters the subcutaneous tissue, travels to the right ventricle, dies and then embolizes the pulmonary vessels causing a small pulmonary infarction, which subsequently appears as a solitary nodule. Although these nodules are usually identified incidentally by chest radiography in asymptomatic patients, the lesion is generally presumed to be neoplastic. Diagnosis is made by surgical excision. Awareness of this benign entity is important in the differential diagnosis of pulmonary coin-lesions. [Copyright &y& Elsevier]

Published
2002
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39. Cell proliferation in 3,800 node-negative breast cancers: Concistency over time of biological and clinical information provided by <SUP>3</SUP>H-Thymidine labelling index

Author

Silvestrini, Rosella, Daidone, Maria Grazia, Luisi, Antonella, Mastore, Marinella, Leutner, Monica, and Salvadori, Bruno

Abstract

For breast cancer, many prognostic markers that initially appeared promising have failed to maintain their clinical predictive value. Few reports have analyzed the consistency over time of biological and clinical information provided by biomarkers. Tumour cell proliferation has acquired relevance as an indicator of prognosis and of response to treatment. Since its clinical role has been investigated for some decades, cell proliferation represents an ideal marker for an over-time validation. In 3,800 node-negative breast cancers recruited between 1972 and 1991, the consistency of information provided by the 3H-thymidine labelling index (TLI), in terms of basic relations with other clinico-pathological and biological variables and clinical predictivity, was evaluated using a combined analysis of results previously published by our group for distinct series of patients. Clinical predictivity was analyzed on a subset of 2,067 patients given local-regional therapy until relapse and followed for a median time from 6 to 10 years. Over the entire period TLI maintained a weak direct relation with tumour size and an inverse strong relation with steroid receptors. An increase in TLI was observed for tumours in post-menopausal patients up to the mid 1980s. During 3 different accrual periods (1972–1983; 1984–1987; 1988–1991), TLI was a consistent and independent predictor of relapse-free time, distant metastasis and overall survival, regardless of its consideration as a continuous variable or with a cutoff value of 3%. The reproducibility of our results over time provides support to the consistency of the methodology used and of the biological and clinical information obtained when using TLI as an indicator of breast cancer cell proliferation. Int. J. Cancer 74:122–127. © 1997 Wiley-Liss, Inc.

Published
1997
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40. FRI158 - Accuracy of liver stiffness measurement in assessing liver fibrosis in naive patients with primary biliary cholangitis.

Author

Cristoferi, Laura, Nardi, Alessandra, Viganò, Mauro, Rigamonti, Cristina, Degasperi, Elisabetta, Cardinale, Vincenzo, Labanca, Sara, Zucchini, Nicola, Leutner, Monica, Venere, Rosanna, Picciotto, Antonino, Cazzagon, Nora, Lucà, Martina, Overi, Diletta, Gerussi, Alessio, D'Amato, Daphne, O'Donnell, Sarah Elisabeth, Cerini, Federica, De Benedittis, Carla, and Cadamuro, Massimiliano

Subjects
*LIVER, *FIBROSIS, *HEPATOLOGY
Published
2020
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41. Cutaneous extramedullary hematopoiesis.

Author

Miglino B, Tiberio R, Boggio P, Astolfi S, Leutner M, and Colombo E

Subjects
Aged, Humans, Leukemia, Myeloid, Acute pathology, Male, Skin Diseases pathology, Hematopoiesis, Extramedullary, Leukemia, Myeloid, Acute diagnosis, Primary Myelofibrosis pathology, Skin Diseases diagnosis
Published
2017
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