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Albumin-bilirubin score: an additional tool for the management of patients with hepatocellular carcinoma
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Refining selection criteria to further increase survival benefit in liver transplantation for unresectable colorectal liver metastases
Full text linkiver transplantation (LT) for hepatocellular carcinoma (HCC) was characterized in its early experience by high recurrence rates due to extensive tumor burden (1). Only after the adoption of Milan criteria (2), LT was recognized as a standard treatment for HCC (3). Besides HCC, other hepatic malignancies were proposed to be treated in the past with LT but due to the poor results observed (4), these indications were abandoned. Among them, colorectal liver metastases (CRLM) were considered an absolute contraindication until recently.
In June 2019, Dueland and colleagues published in Annals of Surgery a case series of 15 LT for unresectable CRLM with an estimated 5-year overall survival (OS) of 83% (5). This trial was named SECA-II and followed the previous SECA-I study (6). SECA-I was published 6 years before and showed a 5-year OS of 60% in 21 patients submitted to LT for unresectable CRLM. Four independent predictors of survival were identified, the so-called “Oslo criteria”: maximal tumor diameter <5.5 cm, time from primary cancer surgery >2 years, carcinoembryonic antigen (CEA) levels <80 μg/L and no progressive disease under chemotherapy. By applying these criteria in SECA-II, patients of the second trial had at the time of LT a significantly lower number of metastatic lesions (5 vs. 8), size of largest liver lesion (24 vs. 45 mm), preoperative CEA levels (2 vs. 15 μg/L) and longer time between primary tumor resection and LT (22.6 vs. 16.8 months) compared to SECA-I patients. However, if we look to table 2, radiological tumor features were significantly worse at diagnosis. The final tumor burden was the consequence of a partial response to neo-adjuvant therapies: patient in SECA-II trial had a 30% response according to RECIST criteria after chemotherapy or less (10–20%) in case of bridging treatments as transarterial chemoembolization or radioembolization. Response to chemotherapy in CRLM seems to be fundamental in selecting a more or less aggressive disease from the biological point of view, especially if a long waiting time before LT has to be expected. Similar is the prognostic value of the dynamic response to locoregional treatments, together with alpha-fetoprotein (AFP) and morphologic characteristics, to predict survival and recurrence in HCC patients (7). Such a refinement of selection criteria also in LT for CRLM turned into better OS as well as longer disease-free survival (DFS) in SECA-II: 1-year DFS increased from 35% to 53% with 4 patients (26.7%) having no recurrence 31 to 49 months after LT. Moreover, most of recurrences occurred in the lung (n=6) and were amenable of resection in almost all cases (5 out 6). Tumor growth was again controlled through the antiangiogenic activity of sirolimus (mTOR inhibitor) but, compared to SECA-I, it was introduced only after 4–6 weeks of tacrolimus, likely due to the occurrence of a high rate of hepatic artery thrombosis and rejection [reported in the literature to be associated with the administration of mTOR inhibitors (8)] in the first trial.
The good results showed by Dueland et al. can also be attributed to the low number of right-sided primary tumors (n=1) and KRAS mutations (n=1) included in the final study population, both of them already recognized as the two the most important prognostic factors for survival after liver resection (9,10). However, the impact of KRAS/BRAF mutation status on survival after LT is unknown, since mutational analysis was not performed at the time of SECA-I trial. On the other hand, a surrogate marker of tumor biology, the liver 18FDG-PET uptake rate, was lower in SECA-II compared to SECA-I. Only time of detection of hepatic metastases was reported to be more unfavourable in SECA-II (synchronous disease in 93% vs. 81% of cases).
The major challenge of LT for CRLM is represented by the shortage of organ donors which limits the wide application of this approach. New strategies are under investigation in the field of LT to expand the donor pool such as hypo/normothermic perfusion to restore borderline liver grafts or novel surgical techniques using auxiliary liver grafts, implanted either orthotopically or heterotopically (11,12). However, if allocation of organs for HCC patients should be based on the concept of transplant benefit (13), i.e., allocating the one available organ to the patient with the largest difference in posttransplant and waiting list lifetime, the survival gain obtained by LT is potentially greater in the setting of unresectable CRLM, given that the only alternative therapy for these patients is represented by palliative chemotherapy with 5-year OS of about 10% (14). Therefore, in theory, CRLM and HCC could equally compete each other given also that OS obtained by the Scandinavian group has been demonstrated to be similar or even higher than that one observed in HCC patients (11).
We do not know whether it is time to push the boundaries of liver transplant for unresectable CRLM but for sure, research should aim to refine selection criteria to further increase survival benefit of these patients who otherwise do not have any other chance of cure. Future studies, including prospective or randomized controlled multicenter trials, are awaited while others are already ongoing
Efficacy of radiofrequency ablation of hepatocellular carcinoma prior to liver transplantation and the need for competing-risk analysis
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Resection or ablation for very early hepatocellular carcinoma and the fundamental problem of causal inference
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Regeneration Techniques: TSH and ALPPS
No full textWhen the size of the future liver remnant is regarded to be insufficient to sustain liver function in the postoperative course, techniques of portal vein occlusion such as portal vein embolization or portal vein ligation can be used to increase the residual liver volume in the context of a classical two-stage hepatectomy or “associating liver partition and portal vein ligation for staged hepatectomy” procedure
99mTc-Mebrofenin Hepatobiliary Scintigraphy Combined With SPECT/CT to Assess Liver Function in Heterotopic Segmental Liver Transplantation in the Splenic Fossa
No full textABSTRACT: Recent studies have shown that the inclusion of a noninvasive and low-cost functional test such as hepatobiliary scintigraphy is considered more reliable than volume alone to predict posthepatectomy liver failure especially in light of new liver regeneration techniques. We herein reported the unique case of a 40-year-old man who underwent heterotopic liver transplantation of segments 2 and 3 in the splenic fossa after splenectomy for unresectable colorectal liver metastases. 99mTc-mebrofenin hepatobiliary scintigraphy combined with SPECT/CT was performed after liver transplantation to monitor graft function and regeneration before removal of the native liver
Fluorescence Cholangiography Using Indocyanine Green Improves the Identification of Biliary Structures During Laparoscopic Cholecystectomy
No full textBackground: This cross-sectional survey aimed to determine whether fluorescence cholangiography using indocyanine green (ICG-FC) can improve the detection of the cystic duct and the main bile duct during laparoscopic cholecystectomy (LC). Methods: The survey was distributed to 214 surgeons (residents/faculties) in 2021. The confidence in the identification of the cystic duct and of the main bile duct was elicited on a 10-point Likert scale before/after the use of ICG-FC. This was repeated for three LCs ranging from a procedure deemed easy to a LC for acute cholecystitis. Results: There were 149 responses. ICG-FC increased the responders' confidence in identifying the cystic duct, raising the median value from 6 (IQR, 5-8) with white light up to 9 (IQR, 9-10) with ICG-FC (paired p < 0.001). This increase was even more evident when identifying the main bile duct, where the median confidence value increased from 5 (IQR, 4-7) with white light to 9 (IQR, 8-10) with the use of ICG-FC (p < 0.001). ICG-FC significantly increased the detection of residents of the main bile duct in case of intermediate difficulty LCs and in LCs for acute cholecystitis. Conclusions: The results support that the use of near-infrared imaging can ameliorate detection of biliary structures, especially of the main bile duct and this was particularly true for young surgeons and in more complex situations
Liver and Vena Cava En Bloc Resection for an Invasive Leiomyosarcoma Causing Budd-Chiari Syndrome, Under Veno-Venous Bypass and Liver Hypothermic Perfusion : Liver Hypothermic Perfusion and Veno-Venous Bypass for Inferior Vena Cava Leiomyosarcoma
No full textBackground. Leiomyosarcoma of vascular origin is a rare tumor, occurring mainly in the inferior vena cava (IVC). When involving the hepatic vein confluence, it often causes Budd–Chiari syndrome, and IVC removal with a complex hepatectomy is required (Mingoli in J Am Coll Surg 211:145–146, 2010; Griffin in J Surg Oncol 34:53–60, 1987; Heaney in Ann Surg 163:237–241, 1966; Fortner in
Ann Surg 180:644–652, 1974).
Methods. A 57-year-old male, without previous oncological history, presented with Budd–Chiari syndrome due to a leiomyosarcoma extending to the supra-diaphragmatic IVC and involving the right and middle hepatic veins. The patient did not receive neoadjuvant treatment.
Results. A femoral to superior vena cava veno-venous bypass was inserted, and both a median sternotomy and phreno-laparotomy with right subcostal extension were performed. A hemi-portocaval shunt was created between the right portal branch and the IVC, while a catheter was connected to the left portal branch for cold perfusion. Under extracorporeal circulation, the IVC was sectioned
after infrahepatic and supra-diaphragmatic cross-clamping. The left liver was flushed with Celsior solution and packed with ice. A right trisectionectomy extended to the caudate lobe with en bloc vena cava removal was performed. The IVC was replaced by a cryopreserved aortic homograft, to which the stump of the left hepatic vein was anastomosed. Bypass duration, warm and cold liver ischemia, and operation time were 280 min, 8 min, 112 min, and 11 h, respectively. Duct-to-duct biliary anastomosis tutored by aT-tube was performed, and the patient was discharged on postoperative day 29, without major complications. After 16 months free of disease, the patient developed bilateral lung metastases. After 4 years the patient is still alive and receiving systemic chemotherapy.
Conclusions. Leiomyosarcoma of the IVC involving the hepatic veins can be treated with extended hepatectomy and removal of the IVC through extracorporeal circulation
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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