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  1. Article ; Online: Long-term outcomes of resection versus transplantation for neuroendocrine liver metastases meeting the Milan criteria.

    Maspero, Marianna / Rossi, Roberta Elisa / Sposito, Carlo / Coppa, Jorgelina / Citterio, Davide / Mazzaferro, Vincenzo

    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

    2022  Volume 22, Issue 11, Page(s) 2598–2607

    Abstract: Liver resection (LR) is considered the treatment of choice for resectable neuroendocrine liver metastases (NELM), while liver transplantation (LT) is currently reserved for highly selected unresectable patients. We retrospectively analyzed data from ... ...

    Abstract Liver resection (LR) is considered the treatment of choice for resectable neuroendocrine liver metastases (NELM), while liver transplantation (LT) is currently reserved for highly selected unresectable patients. We retrospectively analyzed data from consecutive patients undergoing either curative resection or transplantation for liver-only NELM meeting Milan criteria at a single center between 1984 and 2019. Patients who fit Milan criteria were 48 in the transplantation group and 56 in the resection group. After a median follow-up of 158 months for the transplantation group and 126 for the resection group, the 10-year survival rate was 93% for transplantation and 75% for resection (p = .007). The 10-year disease-free survival rate was 52% for transplantation and 18% for resection (p < .001). Transplantation was associated with improved survival at univariate analysis. The median disease-free interval between surgery and recurrence was 78 months for transplantation vs. 24 months for resection (p < .001). The transplantation group had more multisite recurrences (12/25, 48% vs. 5/42, 12% in the resection group, p = .001), while most recurrences in the resection group were intra-hepatic (37/42, 88%, versus 2/25, 8% in the transplantation group). In conclusion, LT was associated with improved survival outcomes in NELM meeting the Milan criteria compared with LR.
    MeSH term(s) Humans ; Carcinoma, Hepatocellular/surgery ; Retrospective Studies ; Liver Neoplasms/pathology ; Hepatectomy ; Liver Transplantation ; Neoplasm Recurrence, Local/surgery
    Language English
    Publishing date 2022-08-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2060594-8
    ISSN 1600-6143 ; 1600-6135
    ISSN (online) 1600-6143
    ISSN 1600-6135
    DOI 10.1111/ajt.17156
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    Zs.A 5542: Show issues Location:
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  2. Article: Liver Transplantation for Hepatic Metastases from Colorectal Cancer: Current Knowledge and Open Issues.

    Maspero, Marianna / Sposito, Carlo / Virdis, Matteo / Citterio, Davide / Pietrantonio, Filippo / Bhoori, Sherrie / Belli, Filiberto / Mazzaferro, Vincenzo

    Cancers

    2023  Volume 15, Issue 2

    Abstract: More than 40% of patients with colorectal cancer present liver metastases (CRLM) during the course of their disease and up to 50% present with unresectable disease. Without surgical interventions, survival for patients treated with systemic therapies ... ...

    Abstract More than 40% of patients with colorectal cancer present liver metastases (CRLM) during the course of their disease and up to 50% present with unresectable disease. Without surgical interventions, survival for patients treated with systemic therapies alone is dismal. In the past, liver transplantation (LT) for patients with unresectable CRLM failed to show any survival benefit due to poor selection, ineffective chemotherapeutic regimens, unbalanced immunosuppression and high perioperative mortality. Since then and for many years LT for CRLM was abandoned. The turning point occurred in 2013, when the results from the Secondary Cancer (SECA I) pilot study performed at Oslo University were published reporting a 60% 5-year overall survival after LT in patients with unresectable CRLM. These results effectively reignited the interest in LT as a potential therapy for CRLM, and several trials are undergoing. The aims of this article are to give a comprehensive overview of the available evidence on LT for CRLM, discuss the open issues in this rapidly evolving field, and highlight possible ways to address the future of this fascinating therapeutic alternative for selected patients with CRLM.
    Language English
    Publishing date 2023-01-05
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15020345
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  3. Article ; Online: The Role of Liver Transplantation in the Treatment of Liver Metastases from Neuroendocrine Tumors.

    Citterio, Davide / Coppa, Jorgelina / Sposito, Carlo / Busset, Michele Droz Dit / Virdis, Matteo / Pezzoli, Isabella / Mazzaferro, Vincenzo

    Current treatment options in oncology

    2023  Volume 24, Issue 11, Page(s) 1651–1665

    Abstract: Opinion statement: Transplant oncology is a new field of medicine referred to the use of solid organ transplantation, particularly the liver, to improve prognosis and quality of life in cancer patients. In unresectable, liver-only metastases from ... ...

    Abstract Opinion statement: Transplant oncology is a new field of medicine referred to the use of solid organ transplantation, particularly the liver, to improve prognosis and quality of life in cancer patients. In unresectable, liver-only metastases from neuroendocrine tumors (NETs) of the digestive tract, liver transplantation represents a competitive chance of cure. Due to the limited resource of donated organs, accurate patients' selection is crucial in order to maximize transplant benefit. Several tumor- and patient-related factors should be considered. Among them, primary tumors with a low grade of differentiation (G1-G2 or Ki67 < 10%), located in a region drained by the portal system and removed before transplantation with at least 3-6 months period of disease stability observed before transplant listing, can be considered for transplantation. In case of NET located in the pancreas, extended lymphadenectomy should complement curative pancreatic resection. A number of other features are described in this review of liver transplantation for NET metastases. Comprehensive approach including various forms of non-surgical treatment and detailed planning and timing of total hepatectomy are discussed. Open issues remain on possible expansion of current criteria while maintaining the same long-term benefit demonstrated with the Milan NET criteria with respect to other non-transplant options, with particular reference to liver resection, peptide receptor radionuclide therapy, and locoregional and systemic treatments.
    MeSH term(s) Humans ; Liver Transplantation/methods ; Neuroendocrine Tumors/surgery ; Neuroendocrine Tumors/pathology ; Quality of Life ; Liver Neoplasms/surgery ; Liver Neoplasms/pathology ; Prognosis
    Language English
    Publishing date 2023-10-26
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2057351-0
    ISSN 1534-6277 ; 1527-2729
    ISSN (online) 1534-6277
    ISSN 1527-2729
    DOI 10.1007/s11864-023-01124-w
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    Zs.A 5523: Show issues Location:
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  4. Article ; Online: COVID-19 in long-term liver transplant patients: preliminary experience from an Italian transplant centre in Lombardy.

    Bhoori, Sherrie / Rossi, Roberta Elisa / Citterio, Davide / Mazzaferro, Vincenzo

    The lancet. Gastroenterology & hepatology

    2020  Volume 5, Issue 6, Page(s) 532–533

    MeSH term(s) Aged ; Betacoronavirus/isolation & purification ; COVID-19 ; Coronavirus Infections/mortality ; Humans ; Immunosuppressive Agents/administration & dosage ; Immunosuppressive Agents/adverse effects ; Italy/epidemiology ; Liver Transplantation/adverse effects ; Liver Transplantation/mortality ; Male ; Pandemics ; Pneumonia, Viral/mortality ; SARS-CoV-2 ; Transplant Recipients/statistics & numerical data
    Chemical Substances Immunosuppressive Agents
    Keywords covid19
    Language English
    Publishing date 2020-04-09
    Publishing country Netherlands
    Document type Letter
    ISSN 2468-1253
    ISSN (online) 2468-1253
    DOI 10.1016/S2468-1253(20)30116-3
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  5. Article ; Online: Y

    Rivoltini, Licia / Bhoori, Sherrie / Camisaschi, Chiara / Bergamaschi, Laura / Lalli, Luca / Frati, Paola / Citterio, Davide / Castelli, Chiara / Mazzaferro, Vincenzo

    Gut

    2022  Volume 72, Issue 2, Page(s) 406–407

    MeSH term(s) Humans ; Carcinoma, Hepatocellular/radiotherapy ; Liver Neoplasms/radiotherapy ; Embolization, Therapeutic ; Immunotherapy
    Language English
    Publishing date 2022-05-04
    Publishing country England
    Document type Letter ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 80128-8
    ISSN 1468-3288 ; 0017-5749
    ISSN (online) 1468-3288
    ISSN 0017-5749
    DOI 10.1136/gutjnl-2021-326869
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    Zs.A 160: Show issues Location:
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  6. Article ; Online: Therapeutic strategies for post-transplant recurrence of hepatocellular carcinoma.

    Sposito, Carlo / Citterio, Davide / Virdis, Matteo / Battiston, Carlo / Droz Dit Busset, Michele / Flores, Maria / Mazzaferro, Vincenzo

    World journal of gastroenterology

    2022  Volume 28, Issue 34, Page(s) 4929–4942

    Abstract: Despite stringent selection criteria, hepatocellular carcinoma recurrence after liver transplantation (LT) still occurs in up to 20% of cases, mostly within the first 2-3 years. No adjuvant treatments to prevent such an occurrence have been developed so ... ...

    Abstract Despite stringent selection criteria, hepatocellular carcinoma recurrence after liver transplantation (LT) still occurs in up to 20% of cases, mostly within the first 2-3 years. No adjuvant treatments to prevent such an occurrence have been developed so far. However, a balanced use of immunosuppression with minimal dose of calcineurin inhibitors and possible addition of mammalian target of rapamycin inhibitors is strongly advisable. Moreover, several pre- and post-transplant predictors of recurrence have been identified and may help determine the frequency and duration of post-transplant follow-up. When recurrence occurs, the outcomes are poor with a median survival of 12 mo according to most retrospective studies. The factor that most impacts survival after recurrence is timing (within 1-2 years from LT according to different authors). Several therapeutic options may be chosen in case of recurrence, according to timing and disease presentation. Surgical treatment seems to provide a survival benefit, especially in case of late recurrence, while the benefit of locoregional treatments has been suggested only in small retrospective studies. When systemic treatment is indicated, sorafenib has been proved safe and effective, while only few data are available for lenvatinib and regorafenib in second line. The use of immune checkpoint inhibitors is controversial in this setting, given the safety warnings for the risk of acute rejection.
    MeSH term(s) Calcineurin Inhibitors ; Carcinoma, Hepatocellular/drug therapy ; Carcinoma, Hepatocellular/surgery ; Humans ; Immune Checkpoint Inhibitors ; Liver Neoplasms/drug therapy ; Liver Neoplasms/surgery ; Neoplasm Recurrence, Local/therapy ; Retrospective Studies ; Sorafenib/therapeutic use ; TOR Serine-Threonine Kinases
    Chemical Substances Calcineurin Inhibitors ; Immune Checkpoint Inhibitors ; Sorafenib (9ZOQ3TZI87) ; TOR Serine-Threonine Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2022-08-19
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2185929-2
    ISSN 2219-2840 ; 1007-9327
    ISSN (online) 2219-2840
    ISSN 1007-9327
    DOI 10.3748/wjg.v28.i34.4929
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    Zs.A 6039: Show issues Location:
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  7. Article ; Online: No benefit after neoadjuvant chemoradiation in stage IV rectal cancer: A propensity score-matched analysis on a real-world population.

    Milito, Pamela / Sorrentino, Luca / Pietrantonio, Filippo / Di Russo, Anna / Citterio, Davide / Mazzaferro, Vincenzo / Cosimelli, Maurizio

    Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver

    2021  Volume 53, Issue 8, Page(s) 1041–1047

    Abstract: Background: Stage IV rectal cancer occurs in 25% of patients and locoregional control of primary tumor is usually poorly considered, since priority is the treatment of metastatic disease.: Aims: This study evaluates impact of neoadjuvant ... ...

    Abstract Background: Stage IV rectal cancer occurs in 25% of patients and locoregional control of primary tumor is usually poorly considered, since priority is the treatment of metastatic disease.
    Aims: This study evaluates impact of neoadjuvant chemoradiation followed by surgery (nCHRTS) vs. upfront surgery on locoregional control and overall survival in stage IV rectal cancer.
    Methods: All patients diagnosed with stage IV rectal carcinoma between 2009 and 2019, undergone elective surgery at the National Cancer Institute of Milan (Italy), were included. Propensity score-based matching was performed between the two study groups. Loco-regional recurrence-free survival (LRRFS) and overall survival (OS) were analysed using Kaplan-Meyer method.
    Results: A total of 139 patients were analyzed. After propensity score matching, 88 patients were included in the final analysis. The 3-yr LRRFS rates were 80.3% for nCHRTS vs. 90.4% for upfront surgery patients (p = 0.35). The 3-yr OS rates were respectively 81.8% vs. 58% (p = 0.36). KRAS mutation (HR 2.506, p = 0.038) and extra-liver metastases (HR 4.308, p = 0.003) were both predictive of worse OS in univariate analysis.
    Conclusion: The present study failed to demonstrate a significant impact of nCHRTS on LRRFS or OS in stage IV rectal cancer.
    MeSH term(s) Chemoradiotherapy, Adjuvant/mortality ; Databases, Factual ; Female ; Humans ; Italy ; Kaplan-Meier Estimate ; Liver Neoplasms/mortality ; Liver Neoplasms/secondary ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Predictive Value of Tests ; Proctectomy/methods ; Proctectomy/mortality ; Propensity Score ; Prospective Studies ; Rectal Neoplasms/mortality ; Rectal Neoplasms/pathology ; Rectal Neoplasms/therapy ; Retrospective Studies ; Survival Rate ; Treatment Outcome
    Language English
    Publishing date 2021-01-22
    Publishing country Netherlands
    Document type Evaluation Study ; Journal Article
    ZDB-ID 1459373-7
    ISSN 1878-3562 ; 1125-8055
    ISSN (online) 1878-3562
    ISSN 1125-8055
    DOI 10.1016/j.dld.2021.01.013
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    Zs.A 1134: Show issues Location:
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  8. Article ; Online: The role of lymphadenectomy in the surgical treatment of intrahepatic cholangiocarcinoma: A review.

    Sposito, Carlo / Droz Dit Busset, Michele / Virdis, Matteo / Citterio, Davide / Flores, Maria / Bongini, Marco / Niger, Monica / Mazzaferro, Vincenzo

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

    2021  Volume 48, Issue 1, Page(s) 150–159

    Abstract: Cholangiocarcinoma is the second most common primary tumor of the liver. The incidence and mortality of its intrahepatic form has been increasing over the past 2 decades. Currently, the only available curative treatment for intrahepatic ... ...

    Abstract Cholangiocarcinoma is the second most common primary tumor of the liver. The incidence and mortality of its intrahepatic form has been increasing over the past 2 decades. Currently, the only available curative treatment for intrahepatic cholangiocarcinoma is surgical resection. There is still no prospective evidence to support neoadjuvant systemic treatments in resectable disease, while adjuvant chemotherapy with Capecitabine is currently the only recommended systemic treatment after liver resection based on the results of randomised trial. Despite the implementation of perioperative treatments and improvements in resective surgery, intrahepatic cholangiocarcinoma remains a disease characterized by high incidence of recurrence and poor long-term survival. Lymph node metastases can be found in 45-65% of patients and are one of the most impacting prognostic factors after surgical resection. Preoperative imaging is not always sufficient in assessing lymph node status, thus hepatic pedicle lymphadenectomy can be important to ensure precise staging in surgical patients. An increasing trend in performing lymph node dissection during liver resection for intrahepatic cholangiocarcinoma has been observed in the last 20 years, although its actual efficacy compared to the potential complications remains debated. The current evidence on the prognostic role of the lymph node status, its preoperative predictability, the basis for a correct hepatic pedicle lymphadenectomy and its prognostic role in the surgical treatment of intrahepatic cholangiocarcinoma are presented.
    MeSH term(s) Bile Duct Neoplasms/pathology ; Bile Duct Neoplasms/surgery ; Bile Ducts, Intrahepatic ; Cholangiocarcinoma/pathology ; Cholangiocarcinoma/surgery ; Hepatectomy/methods ; Humans ; Lymph Node Excision/methods ; Lymph Node Ratio ; Lymph Nodes/pathology ; Neoplasm Staging ; Prognosis
    Language English
    Publishing date 2021-08-10
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 632519-1
    ISSN 1532-2157 ; 0748-7983
    ISSN (online) 1532-2157
    ISSN 0748-7983
    DOI 10.1016/j.ejso.2021.08.009
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    Zs.A 1149: Show issues Location:
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    Zs.MO 549: Show issues

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  9. Article ; Online: Gastrinoma and Zollinger Ellison syndrome: A roadmap for the management between new and old therapies.

    Rossi, Roberta Elisa / Elvevi, Alessandra / Citterio, Davide / Coppa, Jorgelina / Invernizzi, Pietro / Mazzaferro, Vincenzo / Massironi, Sara

    World journal of gastroenterology

    2021  Volume 27, Issue 35, Page(s) 5890–5907

    Abstract: Zollinger-Ellison syndrome (ZES) associated with pancreatic or duodenal gastrinoma is characterized by gastric acid hypersecretion, which typically leads to gastroesophageal reflux disease, recurrent peptic ulcers, and chronic diarrhea. As symptoms of ... ...

    Abstract Zollinger-Ellison syndrome (ZES) associated with pancreatic or duodenal gastrinoma is characterized by gastric acid hypersecretion, which typically leads to gastroesophageal reflux disease, recurrent peptic ulcers, and chronic diarrhea. As symptoms of ZES are nonspecific and overlap with other gastrointestinal disorders, the diagnosis is often delayed with an average time between the onset of symptoms and final diagnosis longer than 5 years. The critical step for the diagnosis of ZES is represented by the initial clinical suspicion. Hypergastrinemia is the hallmark of ZES; however, hypergastrinemia might recognize several causes, which should be ruled out in order to make a final diagnosis. Gastrin levels > 1000 pg/mL and a gastric pH below 2 are considered to be diagnostic for gastrinoma; some specific tests, including esophageal pH-recording and secretin test, might be useful in selected cases, although they are not widely available. Endoscopic ultrasound is very useful for the diagnosis and the local staging of the primary tumor in patients with ZES, particularly in the setting of multiple endocrine neoplasia type 1. Some controversies about the management of these tumors also exist. For the localized stage, the combination of proton pump inhibitory therapy, which usually resolves symptoms, and surgery, whenever feasible, with curative intent represents the hallmark of gastrinoma treatment. The high expression of somatostatin receptors in gastrinomas makes them highly responsive to somatostatin analogs, supporting their use as anti-proliferative agents in patients not amenable to surgical cure. Other medical options for advanced disease are super-imposable to other neuroendocrine neoplasms, and studies specifically focused on gastrinomas only are scant and often limited to case reports or small retrospective series. The multidisciplinary approach remains the cornerstone for the proper management of this composite disease. Herein, we reviewed available literature about gastrinoma-associated ZES with a specific focus on differential diagnosis, providing potential diagnostic and therapeutic algorithms.
    MeSH term(s) Gastrinoma/diagnosis ; Gastrinoma/therapy ; Humans ; Multiple Endocrine Neoplasia Type 1 ; Pancreatic Neoplasms/diagnosis ; Pancreatic Neoplasms/therapy ; Retrospective Studies ; Zollinger-Ellison Syndrome/diagnosis ; Zollinger-Ellison Syndrome/therapy
    Language English
    Publishing date 2021-06-27
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2185929-2
    ISSN 2219-2840 ; 1007-9327
    ISSN (online) 2219-2840
    ISSN 1007-9327
    DOI 10.3748/wjg.v27.i35.5890
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  10. Article ; Online: Improved management of grade B biliary leaks after complex liver resections using gadoxetic acid disodium-enhanced magnetic resonance cholangiography.

    Citterio, Davide / Vaiani, Marta / Sposito, Carlo / Rossi, Roberta Elisa / Flores, Maria / Battiston, Carlo / Mazzaferro, Vincenzo

    Surgery

    2021  Volume 170, Issue 2, Page(s) 499–506

    Abstract: Background: Bile leaks occurring after complex liver resection and lasting >1 week (grade B) usually are managed by means of invasive cholangiography either endoscopic or percutaneous, with a substantial risk of procedure-related complications. The aim ... ...

    Abstract Background: Bile leaks occurring after complex liver resection and lasting >1 week (grade B) usually are managed by means of invasive cholangiography either endoscopic or percutaneous, with a substantial risk of procedure-related complications. The aim of this study was to investigate the ability of gadoxetic acid disodium-enhanced magnetic resonance cholangiography to detect postoperative biliary leaks and avoid invasive cholangiography in case of peripheral location of the fistula.
    Methods: Patients with grade B biliary leak after complex liver resection from January 2018 to March 2020 underwent magnetic resonance cholangiography to guide the management of the leak (study group). The primary endpoint was the ability of magnetic resonance cholangiography to reduce the need for invasive cholangiography with respect to similar posthepatectomy leaks collected in the previous 2 years and approached with upfront invasive cholangiography (controls). A series of in-hospital outcomes also were compared.
    Results: Out of 533 liver resections, 11 study patients versus 11 control patients with grade B leaks were compared. Magnetic resonance cholangiography achieved 100% accuracy in detection and location of the leak. Five out of 6 peripheral leaks healed without invasive cholangiography. Overall, 50% reduction in the use of invasive cholangiography was observed in the study versus control patients. Median healing time and hospital stay were 38 and 40 days in patients undergoing invasive cholangiography versus 10 and 11 days in patients treated conservatively (P = .007 and 0.012, respectively). Infection rate and other complications rate were 82% vs 20% (P = .01) and 35% vs 40% (P = .5), respectively.
    Conclusion: Magnetic resonance cholangiography is a safe, precise, noninvasive tool to detect posthepatectomy bile leaks that can help clinicians in decision-making on conservative versus invasive treatment of fistulas.
    MeSH term(s) Adult ; Aged ; Bile ; Biliary Tract Diseases/diagnostic imaging ; Biliary Tract Diseases/etiology ; Biliary Tract Diseases/surgery ; Cholangiography ; Cohort Studies ; Contrast Media ; Female ; Gadolinium DTPA ; Hepatectomy/adverse effects ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Postoperative Complications/diagnostic imaging ; Postoperative Complications/etiology ; Postoperative Complications/surgery
    Chemical Substances Contrast Media ; gadolinium ethoxybenzyl DTPA ; Gadolinium DTPA (K2I13DR72L)
    Language English
    Publishing date 2021-03-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 202467-6
    ISSN 1532-7361 ; 0039-6060
    ISSN (online) 1532-7361
    ISSN 0039-6060
    DOI 10.1016/j.surg.2021.02.018
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