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Article: Resistance to Antiangiogenic Therapy in Hepatocellular Carcinoma: From Molecular Mechanisms to Clinical Impact.

Federico, Piera / Giunta, Emilio Francesco / Tufo, Andrea / Tovoli, Francesco / Petrillo, Angelica / Daniele, Bruno

2022 Volume 14, Issue 24

Abstract: Antiangiogenic drugs were the only mainstay of advanced hepatocellular carcinoma (HCC) treatment from 2007 to 2017. However, primary or secondary resistance hampered their efficacy. Primary resistance could be due to different molecular and/or genetic ... ...

Abstract	Antiangiogenic drugs were the only mainstay of advanced hepatocellular carcinoma (HCC) treatment from 2007 to 2017. However, primary or secondary resistance hampered their efficacy. Primary resistance could be due to different molecular and/or genetic characteristics of HCC and their knowledge would clarify the optimal treatment approach in each patient. Several molecular mechanisms responsible for secondary resistance have been discovered over the last few years; they represent potential targets for new specific drugs. In this light, the advent of checkpoint inhibitors (ICIs) has been a new opportunity; however, their use has highlighted other issues: the vascular normalization compared to a vessel pruning to promote the delivery of an active cancer immunotherapy and the development of resistance to immunotherapy which leads to a better selection of patients as candidates for ICIs. Nevertheless, the combination of antiangiogenic therapy plus ICIs represents an intriguing approach with high potential to improve the survival of these patients. Waiting for results from ongoing clinical trials, this review depicts the current knowledge about the resistance to antiangiogenic drugs in HCC. It could also provide updated information to clinicians focusing on the most effective combinations or sequential approaches in this regard, based on molecular mechanisms.
Language	English
Publishing date	2022-12-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14246245
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Article ; Online: Non-hereditary early onset gastric cancer: An unmet medical need.

Petrillo, Angelica / Federico, Piera / Marte, Gianpaolo / Liguori, Carlo / Seeber, Andreas / Ottaviano, Margaret / Tufo, Andrea / Daniele, Bruno

Current opinion in pharmacology

2023 Volume 68, Page(s) 102344

Abstract: Gastric cancer (GC) is a lethal disease and the diagnosis in the young population is a major challenge from both individual and social point of views. Early-onset GC accounts for ∼5% of GC; among them, 3% are part of a hereditary syndrome and the ... ...

Abstract	Gastric cancer (GC) is a lethal disease and the diagnosis in the young population is a major challenge from both individual and social point of views. Early-onset GC accounts for ∼5% of GC; among them, 3% are part of a hereditary syndrome and the majority are sporadic. However, even if the early-onset forms were less frequent in the past, the increasing number in the last decades has improved the interest and awareness of them in the society and in the scientific community. In particular, the different behaviour and characteristics of early-onset GC suggest that it is a completely different entity, which requires a tailored and personalized management. Here we provide an updated overview about non-hereditary early-onset GC, which is an unmet clinical need today, along with future perspectives in this field.
MeSH term(s)	Humans ; Age of Onset ; Stomach Neoplasms/diagnosis ; Stomach Neoplasms/genetics ; Stomach Neoplasms/therapy ; Early Detection of Cancer ; Genetic Predisposition to Disease
Language	English
Publishing date	2023-01-04
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2037057-X
ISSN	1471-4973 ; 1471-4892
ISSN (online)	1471-4973
ISSN	1471-4892
DOI	10.1016/j.coph.2022.102344
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Article: Efficacy of Surgery for the Treatment of Gastric Cancer Liver Metastases: A Systematic Review of the Literature and Meta-Analysis of Prognostic Factors.

Marte, Gianpaolo / Tufo, Andrea / Steccanella, Francesca / Marra, Ester / Federico, Piera / Petrillo, Angelica / Maida, Pietro

Journal of clinical medicine

2021 Volume 10, Issue 5

Abstract: Background: In the last 10 years, the management of patients with gastric cancer liver metastases (GCLM) has changed from chemotherapy alone, towards a multidisciplinary treatment with liver surgery playing a leading role. The aim of this systematic ... ...

Abstract	Background: In the last 10 years, the management of patients with gastric cancer liver metastases (GCLM) has changed from chemotherapy alone, towards a multidisciplinary treatment with liver surgery playing a leading role. The aim of this systematic review and meta-analysis is to assess the efficacy of hepatectomy for GCLM and to analyze the impact of related prognostic factors on long-term outcomes. Methods: The databases PubMed (Medline), EMBASE, and Google Scholar were searched for relevant articles from January 2010 to September 2020. We included prospective and retrospective studies that reported the outcomes after hepatectomy for GCLM. A systematic review of the literature and meta-analysis of prognostic factors was performed. Results: We included 40 studies, including 1573 participants who underwent hepatic resection for GCLM. Post-operative morbidity and 30-day mortality rates were 24.7% and 1.6%, respectively. One-year, 3-years, and 5-years overall survival (OS) were 72%, 37%, and 26%, respectively. The 1-year, 3-years, and 5-years disease-free survival (DFS) were 44%, 24%, and 22%, respectively. Well-moderately differentiated tumors, pT1-2 and pN0-1 adenocarcinoma, R0 resection, the presence of solitary metastasis, unilobar metastases, metachronous metastasis, and chemotherapy were all strongly positively associated to better OS and DFS. Conclusion: In the present study, we demonstrated that hepatectomy for GCLM is feasible and provides benefits in terms of long-term survival. Identification of patient subgroups that could benefit from surgical treatment is mandatory in a multidisciplinary setting.
Language	English
Publishing date	2021-03-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm10051141
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Article: How to Treat Hepatocellular Carcinoma in Elderly Patients.

Federico, Piera / Giunta, Emilio Francesco / Pappalardo, Annalisa / Tufo, Andrea / Marte, Gianpaolo / Attademo, Laura / Fabbrocini, Antonietta / Petrillo, Angelica / Daniele, Bruno

Pharmaceuticals (Basel, Switzerland)

2021 Volume 14, Issue 3

Abstract: Hepatocellular carcinoma (HCC) is the primary tumour of the liver with the greatest incidence, particularly in the elderly. Additionally, improvements in the treatments for chronic liver diseases have increased the number of elderly patients who might be ...

Abstract	Hepatocellular carcinoma (HCC) is the primary tumour of the liver with the greatest incidence, particularly in the elderly. Additionally, improvements in the treatments for chronic liver diseases have increased the number of elderly patients who might be affected by HCC. Little evidence exists regarding HCC in old patients, and the elderly are still underrepresented and undertreated in clinical trials. In fact, this population represents a complex subgroup of patients who are hard to manage, especially due to the presence of multiple comorbidities. Therefore, the choice of treatment is mainly decided by the physician in the clinical practice, who often tend not to treat elderly patients in order to avoid the possibility of adverse events, which may alter their unstable equilibrium. In this context, the clarification of the optimal treatment strategy for elderly patients affected by HCC has become an urgent necessity. The aim of this review is to provide an overview of the available data regarding the treatment of HCC in elderly patients, starting from the definition of "elderly" and the geriatric assessment and scales. We explain the possible treatment choices according to the Barcelona Clinic Liver Cancer (BCLC) scale and their feasibility in the elderly population.
Language	English
Publishing date	2021-03-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph14030233
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Article ; Online: Risk Prediction in Acute Calculous Cholecystitis: A Systematic Review and Meta-Analysis of Prognostic Factors and Predictive Models.

Tufo, Andrea / Pisano, Michele / Ansaloni, Luca / de Reuver, Philip / van Laarhoven, Kees / Davidson, Brian / Gurusamy, Kurinchi Selvan

Journal of laparoendoscopic & advanced surgical techniques. Part A

2020 Volume 31, Issue 1, Page(s) 41–53

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Cholecystectomy, Laparoscopic/mortality ; Cholecystitis, Acute/diagnosis ; Cholecystitis, Acute/mortality ; Cholecystitis, Acute/pathology ; Cholecystitis, Acute/surgery ; Clinical Decision Rules ; Humans ; Postoperative Complications/diagnosis ; Postoperative Complications/epidemiology ; Postoperative Complications/etiology ; Prognosis ; Risk Assessment ; Risk Factors
Language	English
Publishing date	2020-07-22
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Review ; Systematic Review
ZDB-ID	1381909-4
ISSN	1557-9034 ; 1092-6429
ISSN (online)	1557-9034
ISSN	1092-6429
DOI	10.1089/lap.2020.0151
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Article ; Online: Psoas syndrome: a frequently missed diagnosis.

Tufo, Andrea / Desai, Gautam J / Cox, W Joshua

The Journal of the American Osteopathic Association

2012 Volume 112, Issue 8, Page(s) 522–528

Abstract: Psoas syndrome is an easily missed diagnosis. However, it is important to consider this condition as part of the differential diagnosis for patients presenting with low back pain--particularly for osteopathic physicians, because patients may view these ... ...

Abstract	Psoas syndrome is an easily missed diagnosis. However, it is important to consider this condition as part of the differential diagnosis for patients presenting with low back pain--particularly for osteopathic physicians, because patients may view these practitioners as experts in musculoskeletal conditions. The authors describe the case of a 48-year-old man with a 6-month history of low back pain that had been attributed to "weak core muscles." The diagnosis of psoas syndrome was initially overlooked in this patient. After the correct diagnosis was made, he was treated by an osteopathic physician using osteopathic manipulative treatment, in conjunction with at-home stretches between office treatments. At his 1-month follow-up appointment, he demonstrated continued improvement of symptoms and a desire for further osteopathic manipulative treatment.
MeSH term(s)	Diagnosis, Differential ; Exercise Therapy ; Humans ; Low Back Pain/etiology ; Low Back Pain/pathology ; Low Back Pain/therapy ; Male ; Manipulation, Osteopathic/methods ; Middle Aged ; Osteopathic Physicians ; Pain, Intractable/etiology ; Pain, Intractable/pathology ; Pain, Intractable/therapy ; Psoas Muscles/pathology ; Spasm/diagnosis ; Spasm/pathology ; Spasm/therapy ; Syndrome
Language	English
Publishing date	2012-08-15
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	410350-6
ISSN	1945-1997 ; 0003-0287 ; 0098-6151
ISSN (online)	1945-1997
ISSN	0003-0287 ; 0098-6151
DOI	10.7556/jaoa.2012.112.8.522
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Article: Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: Current Status and Novel Perspectives.

Federico, Piera / Petrillo, Angelica / Giordano, Pasqualina / Bosso, Davide / Fabbrocini, Antonietta / Ottaviano, Margaret / Rosanova, Mario / Silvestri, Antonia / Tufo, Andrea / Cozzolino, Antonio / Daniele, Bruno

Cancers

2020 Volume 12, Issue 10

Abstract: Immune checkpoint inhibitors (ICIs) represent a promising treatment for many kinds of cancers, including hepatocellular carcinoma (HCC). The rationale for using ICIs in HCC is based on the immunogenic background of hepatitis and cirrhosis and on the ... ...

Abstract	Immune checkpoint inhibitors (ICIs) represent a promising treatment for many kinds of cancers, including hepatocellular carcinoma (HCC). The rationale for using ICIs in HCC is based on the immunogenic background of hepatitis and cirrhosis and on the observation of high programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes in this cancer. Promising data from phase I/II studies in advanced HCC, showing durable objective response rates (~20% in first- and second-line settings) and good safety profile, have led to phase III studies with ICIs as single agents or in combination therapy, both in first and second line setting. While the activity of immunotherapy agents as single agents seems to be limited to an "ill-defined" small subset of patients, the combination of the anti PD-L1 atezolizumab and anti-vascular endothelial growth factor bevacizumab revealed a benefit in the outcomes when compared to sorafenib in the first line. In addition, the activity and efficacy of the combinations between anti-PD-1/anti-PD-L1 antibody and other ICIs, tyrosine kinase inhibitors, or surgical and locoregional therapies, has also been investigated in clinical trials. In this review, we provide an overview of the role of ICIs in the management of HCC with a critical evaluation of the current status and future directions.
Language	English
Publishing date	2020-10-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12103025
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Article ; Online: Follow-up: the evidence.

D'Ugo, Domenico / Biondi, Alberto / Tufo, Andrea / Persiani, Roberto

Digestive surgery

2013 Volume 30, Issue 2, Page(s) 159–168

Abstract: There is currently no consensus on the best strategy for the follow-up of patients who have undergone surgical treatment with curative intent for gastric cancer. The wide variation in recommendations for surveillance among international experts and ... ...

Abstract	There is currently no consensus on the best strategy for the follow-up of patients who have undergone surgical treatment with curative intent for gastric cancer. The wide variation in recommendations for surveillance among international experts and hospital schedules clearly reflects a lack of an established body of evidence on this subject. Consequently, most of the international guidelines aimed at early detection of disease recurrence gloss over details concerning the mode, duration, and intensity of surveillance since they cannot be based on an acceptable grade of recommendation. Very few report anything other than the detection of recurrences or death as the primary endpoints, and, given the poor survival of patients with recurrent gastric cancer, the prognostic effect of early detection seems doubtful. In recent years, an increasing focus on evidence-based medicine, which has coincided with a growing concern about costs and efficiency in medicine, has caused a reevaluation of most surveillance practices. In this paper, we review and discuss the current body of evidence and follow-up practices after curative resection of gastric cancer.
MeSH term(s)	Early Detection of Cancer ; Evidence-Based Medicine ; Follow-Up Studies ; Global Health ; Guidelines as Topic ; Humans ; Neoplasm Recurrence, Local/prevention & control ; Practice Guidelines as Topic ; Prognosis ; Quality of Life ; Stomach Neoplasms/diagnosis ; Stomach Neoplasms/mortality ; Stomach Neoplasms/surgery ; Survival Rate
Language	English
Publishing date	2013
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	605888-7
ISSN	1421-9883 ; 0253-4886
ISSN (online)	1421-9883
ISSN	0253-4886
DOI	10.1159/000350878
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Article ; Online: Changing outlook for colorectal liver metastasis resection in the elderly.

Tufo, Andrea / Dunne, Declan Fj / Manu, Nichola / Lacasia, Carmen / Jones, Louise / de Liguori Carino, Nicola / Malik, Hassan Z / Poston, Graeme J / Fenwick, Stephen W

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology

2018 Volume 45, Issue 4, Page(s) 635–643

Abstract: Background: This study sought to evaluate the impact of the advancements in clinical care, obtained over the last 20 years, for patients aged 70 and older undergoing liver resection for colorectal liver metastases (CRLM).: Methods: Consecutive ... ...

Abstract	Background: This study sought to evaluate the impact of the advancements in clinical care, obtained over the last 20 years, for patients aged 70 and older undergoing liver resection for colorectal liver metastases (CRLM). Methods: Consecutive patients age 70 or older who underwent liver resection for CRLM at Aintree University Hospital (Liverpool, UK) between May 2008 and May 2015 were compared to a dataset of consecutive patients, meeting the same criteria, between 1990 and 2007. An enhanced recovery programme after surgery (ERAS) combined with cardiopulmonary exercise testing (CPET) was introduced in January 2008. Results: The proportion of patients over 70 years undergoing liver resection for CRLM increased over the study period (6% in 1990, 16.3% in 2000, 26.5% in 2005 and 25.8% in 2007). The patients in the later group were more often treated with neoadjuvant chemotherapy (58 vs 34, p = 0.006) and underwent parenchymal sparing surgery, resulting in fewer major hepatectomies (51 vs 111, p < 0.001) and less perioperative morbidity (49 vs 70, p = 0.043) and mortality (3 vs 9, p = 0.229). Although there was shorter disease free survival (DFS) in the later group (DFS at 1, 3 and 5 years was 52.1%, 31.6%, 29% vs. 71.8%, 49.1%, 44.0%)(p < 0.01), similar overall survival (OS) was achieved (OS at 1, 3 and 5 years was 85.4%, 51.6%, 32.8% vs. 81.7%, 42.1%, 27.3%)(p = 0.21). Conclusions: This study demonstrates that, with modern management (ERAS, CPET, neoadjuvant chemotherapy and parenchymal sparing surgery), a greater number of patients with CRLM, over the age of seventy, can undergo liver resection, with improved perioperative outcomes.
MeSH term(s)	Aged ; Aged, 80 and over ; Chemotherapy, Adjuvant ; Colorectal Neoplasms/pathology ; Disease-Free Survival ; Exercise Test ; Female ; Hepatectomy/methods ; Hepatectomy/trends ; Humans ; Liver Neoplasms/pathology ; Liver Neoplasms/secondary ; Liver Neoplasms/therapy ; Male ; Neoadjuvant Therapy ; Oxygen Consumption ; Perioperative Care ; Survival Rate ; Tumor Burden
Language	English
Publishing date	2018-12-04
Publishing country	England
Document type	Journal Article
ZDB-ID	632519-1
ISSN	1532-2157 ; 0748-7983
ISSN (online)	1532-2157
ISSN	0748-7983
DOI	10.1016/j.ejso.2018.11.024
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Zs.A 1149: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Hepatectomy for octogenarians with colorectal liver metastasis in the era of enhanced recovery.

Tufo, Andrea / Dunne, Declan F J / Manu, Nichola / Joshi, Heman / Lacasia, Carmen / Jones, Louise / Malik, Hassan Z / Poston, Graeme J / Fenwick, Stephen W

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology

2018 Volume 44, Issue 7, Page(s) 1040–1047

Abstract: Background: Concern exists regarding the use of hepatectomy to treat colorectal liver metastasis (CRLM) in octogenarians due to prior studies suggesting elevated morbidity and mortality. Cardiopulmonary exercise testing (CPET) within pre-operative ... ...

Abstract	Background: Concern exists regarding the use of hepatectomy to treat colorectal liver metastasis (CRLM) in octogenarians due to prior studies suggesting elevated morbidity and mortality. Cardiopulmonary exercise testing (CPET) within pre-operative assessment and enhanced recovery after surgery (ERAS) have both been shown to be associated with low morbidity and mortality in patients undergoing hepatectomy. This study sought to compare the outcomes of octogenarians with patients aged 70-79 undergoing hepatectomy for CRLM, within a center utilizing both CPET and ERAS. Methods: Consecutive patients age 70 or older who underwent hepatectomy for CRLM at Aintree University Hospital (Liverpool,UK), between May 2008 and May 2015 were identified from a prospectively maintained cancer database. Data were extracted and comparisons drawn. Results: 127 patients aged 70-79 years and 34 octogenarians underwent respectively 137 and 35 hepatectomy for CRLM. There was no difference in hospital stay (6 days), morbidity and mortality between the groups. OS at 1, 3 and 5 years were 86.7%, 55% and 35.8% for those aged 70-79 compared to 79.4%, 37.3% and 20.4% for the octogenarians (p=0.127). DFS at 1,3 and 5 years was 52.5%, 31.7% and 31.7% for 70-79 group compared to 46.2%, 31.5% and 16.8% for the octogenarians (p=0.838). On multivariate analysis major hepatectomy was associated with an increased risk of post-operative complications, inferior OS and DFS. Chronological age was not a predictor of postoperative complications, poorer OS or DFS. Conclusions: Appropriately selected octogenarians can have similar postoperative outcomes to patients aged 70-79 when undergoing hepatectomy for CRLM using ERAS combined with CPET. This study advocates using CPET and ERAS in the selection and management of octogenarian patients with CRLM undergoing hepatectomy.
MeSH term(s)	Age Factors ; Aged ; Aged, 80 and over ; Clinical Protocols ; Colorectal Neoplasms/pathology ; Disease-Free Survival ; Exercise Test ; Female ; Hepatectomy/methods ; Humans ; Length of Stay ; Liver Neoplasms/secondary ; Liver Neoplasms/surgery ; Male ; Metastasectomy/methods ; Multivariate Analysis ; Patient Selection ; Perioperative Care ; Postoperative Complications/epidemiology ; Preoperative Care ; Retrospective Studies ; Survival Rate ; Treatment Outcome
Language	English
Publishing date	2018
Publishing country	England
Document type	Journal Article
ZDB-ID	632519-1
ISSN	1532-2157 ; 0748-7983
ISSN (online)	1532-2157
ISSN	0748-7983
DOI	10.1016/j.ejso.2018.01.089
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