Impact of Pre-Liver Transplant Treatments on the Imaging Accuracy of HCC Staging and Their Influence on Outcomes.

The outcome of liver transplantation (LT) for hepatocarcinoma (HCC) is strongly influenced by HCC staging, which is based on radiological examinations in a pre-LT setting; concordance between pre-LT radiological and definitive pathological staging remains controversial. To address this issue, we retrospectively analyzed our LT series to assess concordance between radiology and pathology and to explore the factors associated with poor concordance and outcomes. We included all LTs with an HCC diagnosis performed between 2013 and 2018. Concordance (Co group) was defined as a comparable tumor burden in preoperative imaging and post-transplant pathology; otherwise, non-concordance was diagnosed (nCo group). Concordance between radiology and pathology was observed in 32/134 patients (Co group, 24%). The number and diameter of the nodules were higher when nCo was diagnosed, as was the number of pre-LT treatments. Although concordance did not affect survival, more than three pre-LT treatments led to a lower disease-free survival. Patients who met the Milan Criteria (Milan-in patients) were more likely to receive ≥three prior treatments, leading to a lower survival in multi-treated Milan-in patients than in other Milan-in patients. In conclusion, the concordance rate between the pre-LT imaging and histopathological results was low in patients with a high number of nodules. Multiple bridging therapies reduce the accuracy of pre-LT imaging in predicting HCC stages and negatively affect outcomes after LT.

Anatomical liver resection using the ultrasound-guided compression technique in minimal access surgery.

BACKGROUND: Segmental or subsegmental anatomical resection (AR) of hepatocellular carcinoma (HCC) in minimal access liver surgery (MALS) has been technically proposed. The Glissonean approach or dye injection technique are generally adopted. The tumor-feeding portal pedicle compression technique (C-AR) is an established approach in open surgery, but its feasibility in the MALS environment has never been described. METHODS: Eligible patients were prospectively enrolled to undergo laparoscopic or robotic ultrasound-guided C-AR based on HCC location and preoperative identification of a single tumor-feeding portal pedicle. Initial C-AR experience was gained with laparoscopic cases in the beginning of 2020. Following our progressive experience in laparoscopic C-AR, patients requiring AR for HCC were consecutively selected for robotic C-AR. RESULTS: A total of 10 patients underwent minimal access C-AR. All patients had Child-Pugh A HCC. The surgical procedures included 6 laparoscopic and 4 robotic C-AR. Median tumor size was 3.1 cm (range 2-7 cm). All procedures had R0 margin. Postoperative complications were nil. CONCLUSION: C-AR technique is a feasible and promising technique for patients eligible for laparoscopic and robotic AR for HCC. Further data are necessary to validate its applicability to more complex minimal access AR.

Perfusion fluid-related infections in liver transplant recipients: A 5-year, single-center, retrospective study.

BACKGROUND: Perfusion fluid (PRF) is employed in liver transplantation (LTx) to maintain graft viability. Still, it represents a new potential way of infection transmission in LTx recipients (LTRs). Currently, no systematic research has investigated this topic. METHODS: Five-year single-center retrospective study conducted on LTRs from January 2017 to December 2021. We analyzed the incidence of positive PRF culture (PRF+) and perfusion fluid-related infections (PRF-RI) and their associated factors. We also assessed 1-year mortality, both overall and infection-related. RESULTS: Overall, 234 LTx were included. PRF+ were found in 31/234 (13.2%) LTx for a total of 37 isolates, with >1 isolate identified in 5 (2.1%) cases. High-risk microorganisms (Enterobacterales 13/37, Enterococcus spp. 4/37, S. aureus 3/37, P. aeruginosa 2/37) were isolated in 25/37 (67.6%) LTRs, the remaining being coagulase-negative staphylococci (12/37, 32.4%). Antimicrobial prophylaxis was administered to all LTRs, always active against the isolate even if suboptimal in 19 cases (61.3%). PRF-RI developed in 4/234 LTx (1.7%), and prophylaxis was considered suboptimal in 2/4 of them. The isolation of >1 microorganism in PRF culture was associated with an increased risk of developing PRF-RI (OR 37.5 [95%CI 2.6-548.4], p = .01). PRF-RI were associated with longer ICU stays (p = .005) and higher 1-year mortality, both overall and related to infections (p = .001). CONCLUSION: Despite PRF+ being infrequent, only a minority of patients develops PRF-RI. Nonetheless, once occurred, PRF-RI seems to increase morbidity and mortality rates.

Upfront Surgery versus Neoadjuvant Perioperative Chemotherapy for Resectable Colorectal Liver Metastases: A Machine-Learning Decision Tree to Identify the Best Potential Candidates under a Parenchyma-Sparing Policy.

Addressing patients to neoadjuvant systemic chemotherapy followed by surgery rather than surgical resection upfront is controversial in the case of resectable colorectal -liver metastases (CLM). The aim of this study was to develop a machine-learning model to identify the best potential candidates for upfront surgery (UPS) versus neoadjuvant perioperative chemotherapy followed by surgery (NEOS). Patients at first liver resection for CLM were consecutively enrolled and collected into two groups, regardless of whether they had UPS or NEOS. An inverse -probability weighting (IPW) was performed to weight baseline differences; survival analyses; and risk predictions were estimated. A mortality risk model was built by Random-Forest (RF) to assess the best -potential treatment (BPT) for each patient. The characteristics of BPT-upfront and BPT-neoadjuvant candidates were automatically identified after developing a classification -and -regression tree (CART). A total of 448 patients were enrolled between 2008 and 2020: 95 UPS and 353 NEOS. After IPW, two balanced pseudo-populations were obtained: UPS = 432 and NEOS = 440. Neoadjuvant therapy did not significantly affect the risk of mortality (HR 1.44, 95% CI: 0.95-2.17, p = 0.07). A mortality prediction model was fitted by RF. The BPT was NEOS for 364 patients and UPS for 84. At CART, planning R1vasc surgery was the main factor determining the best candidates for NEOS and UPS, followed by primitive tumor localization, number of metastases, sex, and pre-operative CEA. Based on these results, a decision three was developed. The proposed treatment algorithm allows for better allocation according to the patient's tailored risk of mortality.

Laparoscopic Ultrasound-Guided R1 Vascular Liver Resection for Colorectal Liver Metastases at Caval Confluence.

BACKGROUND: Patients with tumors involving the hepatic vein (HV) at the caval confluence (CC) usually receive major hepatectomies or HV grafting. For colorectal liver metastases (CLM), tumor-vessel detachment (R1vasc) has proven to be oncologically adequate.1-3 However, parenchyma-sparing R1vasc surgery has usually been confined to the open approach. The technical tricks for accomplishing this kind of surgery in laparoscopy are disclosed. METHODS: A patient with a CLM in contact with the middle HV (MHV) and left HV (LHV) at the CC underwent liver resection. No signs of vascular invasion were observed at preoperative imaging. On the basis of the low rate of tumor-vessel regression after chemotherapy,4 technical feasibility, and low tumor burden, patient was considered for upfront surgery. Surgery consisted in: (1) left liver mobilization with full exposure of the CC; (2) identification of the common trunk's root and its encirclement by tape; (3) the use of ultrasound to rule out HV invasion and to define a resection area favoring a transection plane smoothly approaching the point of vascular contact; and (4) careful vascular detachment by blunt dissection in a caudocranial fashion to separate the lesion from HVs. RESULTS: A limited resection of segments, four superior and two with MHV-LHV detachment, was performed. Operation time was 285 min, with 52 min of cumulative Pringle time and 20 ml of blood loss. Postoperative course was uneventful. The in-hospital stay was 6 days. CONCLUSION: Similarly to open surgery, laparoscopic R1vasc surgery for CLM at CC is feasible and represents an alternative to major hepatectomy. HV control by tape is recommended to manage any bleeding that may occur during tumor-vessel detachment.

Association of indirect measurement of cell function by bioimpedance analysis with complications in oncologic hepatic surgery.

BACKGROUND: Bioelectric impedance vector analysis (BIVA) is a reliable tool to assess body composition. The aim was to study the association of BIVA-derived phase angle (PA) and standardized PA (SPA) values and the occurrence of surgery-related morbidity. METHODS: Patients undergoing hepatectomy for cancer in two Italian centers were prospectively enrolled. BIVA was performed the morning of surgery. Patients were then stratified for the occurrence or not of postoperative morbidity. RESULTS: Out of 190 enrolled patients, 76 (40%) experienced postoperative complications. Patients with morbidity had a significant lower PA, SPA, body cell mass, and skeletal muscle mass, and higher extracellular water and fat mass. At the multivariate analysis, presence of cirrhosis (OR 7.145, 95% CI:2.712-18.822, p < 0.001), the Charlson comorbidity index (OR 1.236, 95% CI: 1.009-1.515, p = 0.041), the duration of surgery (OR 1.004, 95% CI:1.001-1.008, p = 0.018), blood loss (OR 1.002. 95% CI: 1.001-1.004, p = 0.004), dehydration (OR 10.182, 95% CI: 1.244-83.314, p = 0.030) and SPA < -1.65 (OR 3.954, 95% CI: 1.699-9.202, p = 0.001) were significantly and independently associated with the risk of complications. CONCLUSION: Introducing BIVA before hepatic resections may add valuable and independent information on the risk of morbidity.

Ultrasound-guided anatomical liver resection using a compression technique combined with indocyanine green fluorescence imaging.

BACKGROUND: Anatomical resection (AR) is a recommended surgical treatment for hepatocellular carcinoma (HCC). However, the conventional procedure (dye injection) for AR is difficult to reproduce. As an alternative, the tumour-feeding portal pedicle compression technique (finger-compression technique) has been proposed as an easy and reversible procedure. Here, we propose a new method combining indocyanine green (ICG) imaging with the finger-compression technique. METHODS: Eligible patients were prospectively enrolled to undergo ICG compression (ICG-C) anatomical hepatectomy for HCC. RESULTS: Fifteen patients underwent AR using the ICG-C technique. Overall, the surgical procedures included six segmentectomies, seven subsegmentectomies, and two right posterior sectionectomies. The median tumour size was 5.8 cm (range 2-7 cm). All procedures had an R0 margin. There were no major complications among patients, and minor morbidity occurred in three patients. CONCLUSIONS: ICG-C is a safe, feasible and effective technique for patients eligible for AR.

Prediction of remnant liver volume using 3D simulation software in patients undergoing R1vasc parenchyma-sparing hepatectomy for multiple bilobar colorectal liver metastases: reliability, clinical impact, and learning curve.

BACKGROUND: Assessment of the future liver remnant (FLR) is routinely performed before major hepatectomy. In R1-vascular one-stage hepatectomy (R1vasc-OSH), given the multiplanar dissection paths, the FLR is not easily predictable. Preoperative 3D-virtual casts may help. We evaluated the predictability of the FLR using the 3D-virtual cast in the R1vasc-OSH for multiple bilobar colorectal liver metastases (CLM). METHODS: Thirty consecutive patients with multiple bilobar CLMs scheduled for R1vasc-OSH were included. Predicted and real-FLRs were compared. Propensity score-matched analysis was used to determine the impact of 3D-virtual cast on postoperative complications. RESULTS: Median number of CLM and resection areas were 12 (4-33) and 3 (1-8). Median predicted-FLR was 899 ml (558-1157) and 60% (42-85), while for the real-FLR 915 ml (566-1777) and 63% (43-87). Median discrepancy between predicted and real-FLR was -0.6% (p = 0.504), indicating a slight tendency to underestimate the FLR. The difference was more evident in more than 12 CLMs (p = 0.013). A discrepancy was not evident according to the number of resection areas (p = 0.316). No mortality occurred. Patients in virtual-group had lower major complications compared to nonvirtual-group (0% vs 18%, p-value 0.014). CONCLUSION: FLR estimation based on 3D-analysis is feasible, provides a safe surgery and represents a promising method in planning R1vasc-OSH for patients with multiple bilobar CLMs.

Effects of volume on outcome in hepatobiliary surgery: a review with guidelines proposal.

The positive relationship between volume and outcome in hepatobiliary surgery has been demonstrated for many years. As for other complex surgical procedures, both improved short- and long-term outcomes have been associated with a higher volume of procedures. However, whether the centralization of complex hepatobiliary procedures makes full sense because it should be associated with higher quality of care, as reported in the literature, precise criteria on what to centralize, where to centralize, and who should be entitled to perform complex procedures are still missing. Indeed, despite the generalized consensus on centralization in hepatobiliary surgery, this topic remains very complex because many determinants are involved in such a centralization process, of which some of them cannot be easily controlled. In the context of different health systems worldwide, such as national health systems and private insurance, there are different stakeholders that demand different needs: politicians, patients, surgeons, institutions and medical associations do not always have the same needs. Starting from a review of the literature on centralization in hepatobiliary surgery, we will propose some guidelines that, while not data-driven due to low evidence in the literature, will be based on good clinical practice.

Is the outcome after hepatectomy for transitional hepatocholangiocarcinoma different from that of hepatocellular carcinoma and mass-forming cholangiocarcinoma? A case-matched analysis.

Hepatocholangiocarcinoma (HCC-CC) is a rare malignancy containing features of both hepatocellular carcinoma (HCC) and mass-forming cholangiocarcinoma (MFCCC), of which the outcome after hepatectomy remains to be clarified. The aim of this study was to analyze the characteristics and outcomes of patients with transitional HCC-CC and compare them with those of patients with HCC and MFCCC. Our prospectively maintained database was queried, and 14 transitional HCC-CC patients were identified over a total of 406 consecutive hepatic resections. A 1:1:1 match was performed with HCC and MFCCC patients operated in the same period. A total of 42 patients were matched according to tumor stage (T1-2-3, N0, M0), number of tumors, R0 resection, no 90-day mortality, and follow-up. Primary endpoints were disease-free survival (DFS) and overall survival (OS). Disease-free survival rates at 1-, 3-, and 5-year were 71.4%, 57.1%, 35.7% for transitional HCC-CC patients; 85.7%, 40.4%, 10.1% for HCC patients; 85.1%, 34.0%, 22.7% for MFCCC patients (5-year DFS: HCC-CC vs. HCC, p = 0.575; HCC-CC vs. MFCCC, p = 0.766, respectively). Similarly, OS rates at 1-, 3-, and 5-year were 92.9%, 71.4%, 64.3% for transitional HCC-CC patients; 100%, 64.3%, 41.7% for HCC patients; 100%, 54.5%, 43.6% for MFCCC patients (5-year OS: HCC-CC vs. HCC, p = 0.891; HCC-CC vs. MFCCC, p = 0.673, respectively). When accurately matched with respect to tumor burden, transitional HCC-CC patients show similar outcomes to those of HCC and MFCCC patients. Further evaluations of differences in tumor biology are necessary to better characterize the prognosis of transitional HCC-CC patients.

Vascular Remodeling of Visceral Arteries Following Interruption of the Splenic Artery During Liver Transplantation.

Splenic artery (SA) ligation can be performed during liver transplantation (LT) to avoid portal hyperperfusion, which is involved in the pathogenesis of both small-for-size and SA syndrome. The SA can also be used as an inflow for arterial reconstruction. Exceptionally, SA interruption or agenesis has been associated with positive remodeling of collateral arteries supplying the spleen via the left gastric artery (LGA), short gastric vessels, and the gastroepiploic arcade (GEA), with subsequent severe upper gastrointestinal (GI) bleeding. To determine incidence, magnitude, predictors, and clinical implications of vascular remodeling after SA interruption during LT, we identified 465 patients transplanted in the period 2007-2017 who had the SA ligated or interrupted at LT. Among them, 88 had a computed tomography angiography suitable for evaluation of vascular remodeling after LT. The presence of prominent gastric arterial collaterals and the increase in LGA and GEA diameter were evaluated on 2-dimensional axial images and multiplanar reconstructions. Of the 88 patients, 28 (31.8%), 32 (36.4%), and 22 (25.0%) developed gastric collateralization graded as mild, moderate, or severe. Of the patients for whom comparison with pre-LT imaging was possible (n = 54), 51 (94.4%) presented a median 37% and 55% increase in LGA and GEA diameter, respectively. Severe gastric collateralization was associated with lower body mass index (odds ratio, 0.84; 95% confidence interval [CI], 0.71-0.98; P = 0.03), whereas a GEA caliper measurement increase was positively correlated with Model for End-Stage Liver Disease score (r2 = 0.12; 95% CI, 0.65-4.15; P = 0.008). Out of 465 patients, 2 (0.43%) had severe episodes of arterial upper GI bleeding, possibly exacerbated by vascular remodeling. In conclusion, vascular remodeling after SA interruption during LT is frequent and can aggravate GI bleeding during follow-up.

Two-stage hepatectomy after autologous CD133+ stem cells administration: a case report.

Liver resection is the mainstay of treatment for patients with primary and metastatic liver tumors. However, a large majority of patients present for initial medical evaluation with primary and metastatic liver tumors when their cancer is unresectable. Several trials have been undertaken to identify alternative treatments and complementary therapies. In the near future, the field of liver surgery will aim to increase the number of patients that can benefit from resection, since radical removal of the tumor currently provides the sole chance of cure. This paper reports the case of a patient with an advanced colonic cancer in the era of stem cell therapy. In 2011, a 57 years old white Caucasian man with a previous history of non-Hodgkin lymphoma (NHL) was diagnosed with colon cancer and bilobar liver metastases. Following neoadjuvant therapy, the patient was enrolled in a protocol of stem cell administration for liver regeneration. Surgery was initially performed on the primary cancer and left liver lobe. An extended right lobectomy to S1 was then performed after a portal vein embolization (PVE) and stem cell stimulation of the remaining liver. The postoperative course was uneventful and the patient was free of disease after 12 months. Extreme liver resection can provide a safer option and a chance of cure to otherwise unresectable patients when liver regeneration is boosted by PVE and stem cell administration.

Combined use of intraoperative ultrasound and indocyanine green fluorescence imaging to detect liver metastases from colorectal cancer.

OBJECTIVES: Surgical excision is the standard strategy for managing liver metastases from colorectal carcinoma. The achievement of negative (R0) margins is a major determinant of disease-free survival in these patients. Current imaging techniques are of limited value in achieving this goal. A new approach to the intraoperative detection of colorectal liver metastatic tissue based on the emission of indocyanine green (ICG) fluorescence was evaluated. METHODS: A total of 25 consecutive patients with liver metastases from primary colorectal cancers who were eligible for liver resection received a bolus of ICG (0.5 mg/kg body weight) 24 h before surgery. During surgery, ICG fluorescence, which accumulates around lesions as a result of defective biliary clearance, was detected with a near-infrared camera system, the Photodynamic Eye (PDE). Numbers of lesions detected by, respectively, PDE + ICG, intraoperative ultrasound (IOUS) and preoperative computed tomography (CT) were recorded. RESULTS: The near-infrared camera plus ICG revealed a total of 77 metastatic liver nodules. Preoperative CT demonstrated 45 (58.4%) and IOUS showed 55 (71.4%). Preoperative CT and IOUS alone were inferior to the combined use of PDE + ICG and IOUS in the detection of lesions of ≤ 3 mm in size. CONCLUSIONS: This experience suggests that PDE + ICG, combined with IOUS, may represent a safe and effective tool for ensuring the complete surgical eradication of liver metastases from colorectal cancer.