Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) induces a rapid and extensive increase in liver volume. The functional quality of this hypertrophic response has ...been called into question because ALPPS is associated with a substantial incidence of liver failure and high perioperative mortality. This multicenter study aimed to evaluate functional liver regeneration in contrast to volumetric liver regeneration in ALPPS, using technetium-99m hepatobiliary scintigraphy and computed tomography volumetry, respectively.
Patients who underwent ALPPS and hepatobiliary scintigraphy in 6 centers were included. Hepatobiliary scintigraphy data were analyzed centrally at the Academic Medical Center in Amsterdam according to established protocols. Increase in liver function as measured by hepatobiliary scintigraphy after stage 1 of ALPPS was compared with the increase in liver volume. In addition, we analyzed the impact of liver function and volume on postoperative outcomes including liver failure, morbidity, and mortality.
In 60 patients, future liver remnant volume increased by a median 78% (interquartile range 48–110) during a median 8 (interquartile range 6–14) days after stage 1, while function as measured by hepatobiliary scintigraphy increased by a median 29% (interquartile range 1–55) throughout 7 days (interquartile range 6–10) in the 27 patients with paired measurements. After stage 2 of ALPPS, liver failure occurred in 5/60 (8%) patients, severe complications in 24/60 (40%), and mortality occurred in 4/60 (7%).
In ALPPS, volumetry overestimates liver function as measured by hepatobiliary scintigraphy and may be responsible for the high rate of liver failure. Quantitative liver function tests are highly recommended to avoid post hepatectomy liver failure.
Objectives
Effective and non-invasive biomarkers to predict and avoid posthepatectomy liver failure (PHLF) are urgently needed. This systematic review aims to evaluate the efficacy of gadoxetic ...acid–enhanced MRI-derived parameters as an imaging biomarker in preoperative prediction of PHLF.
Methods
A systematic literature search was performed in the databases of PubMed/Medline, Web of Science, Embase, and Cochrane Library up to 11 December 2020. Studies evaluating the incidence of PHLF on patients who underwent hepatectomy with preoperative liver function assessment using gadoxetic acid–enhanced MRI were included. Data was extracted using pre-designed tables. The Quality In Prognostic Studies (QUIPS) tool was adopted to evaluate the risk of bias.
Results
A total of 15 studies were identified for qualitative synthesis and most studies were marked as low to moderate risk of bias in each domain of QUIPS. The most commonly used parameter was relative liver enhancement or its related parameters. The reported incidence of PHLF ranged from 3.9 to 40%. The predictive sensitivity and specificity of gadoxetic acid–enhanced MRI parameters varied from 75 to 100% and from 54 to 93% in ten reported studies. A majority of the studies revealed that the gadoxetic acid–enhanced MRI parameter was a predictor for PHLF.
Conclusions
Gadoxetic acid–enhanced MRI showed a high predictive capacity for PHLF and represents a promising imaging biomarker in prediction of PHLF. Multicenter, prospective trials with large sample size and reliable, unified liver function parameters are required to validate the efficacy of individual liver function parameters.
Key Points
•
There is an obvious heterogeneity of the published studies, not only in variance of MRI liver function parameters but also in indication and extent of the liver resection.
•
Signal intensity (SI)–based parameters derived from gadoxetic acid–enhanced MRI are the commonly used method for PHLF prediction.
•
Gadoxetic acid–enhanced MRI-derived parameters showed high predictive efficacy for PHLF and can potentially serve as a predictor for the incidence of PHLF.
Background
Despite a fast and potent growth of the future liver remnant (FLR), patients operated with associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) are at risk ...of developing posthepatectomy liver failure. In this study, the relation between liver volume and function in ALPPS was studied using a multimodal assessment.
Methods
Nine patients with colorectal liver metastases treated with neoadjuvant chemotherapy and operated with ALPPS were studied with hepatobiliary scintigraphy, computed tomography, indocyanine green clearance test, and serum liver function tests. A comparison between liver volume and function was conducted.
Results
The preoperative FLR volume of 19.5% underestimated the preoperative FLR function of 25.3% (
p
= 0.011). The increase in FLR volume exceeded the increase in function at day 6 after stage 1 (FLR volume increase 56.7% versus FLR function increase 28.2%,
p
= 0.021), meaning that the increase in function was 50% of the increase in volume. After stage 2, functional increase exceeded the volume increase, resulting in similar values 28 days after stage 2.
Conclusions
In the inter-stage period of ALPPS, the high volume increase is not paralleled by a corresponding functional increase. This may in part explain the high morbidity and mortality rates associated with ALPPS. Functional assessment of the FLR is advised.
Plasma fibrinogen and albumin concentrations initially decrease after abdominal surgery. On postoperative days 3–5 fibrinogen concentration returns to the preoperative level or even higher, while ...albumin stays low. It is not known if these altered plasma concentrations reflect changes in synthesis rate, utilization, or both. In particular a low albumin plasma concentration has often been attributed to a low synthesis rate, which is not always the case. The objective of this study was to determine fibrinogen and albumin quantitative synthesis rates in patients undergoing major upper abdominal surgery with and without intact liver size. Patients undergoing liver or pancreatic resection (n = 9+6) were studied preoperatively, on postoperative days 1 and 3–5. De novo synthesis of fibrinogen and albumin was determined; in addition, several biomarkers indicative of fibrinogen utilization were monitored. After hemihepatectomy, fibrinogen synthesis was 2-3-fold higher on postoperative day 1 than preoperatively. On postoperative days 3–5 the synthesis level was still higher than preoperatively. Following major liver resections albumin synthesis was not altered postoperatively compared to preoperative values. After pancreatic resection, on postoperative day 1 fibrinogen synthesis was 5-6-fold higher than preoperatively and albumin synthesis 1.5-fold higher. On postoperative days 3–5, synthesis levels returned to preoperative levels. Despite decreases in plasma concentrations, de novo synthesis of fibrinogen was markedly stimulated on postoperative day 1 after both hemihepatectomies and pancreatectomies, while de novo albumin synthesis remained grossly unchanged. The less pronounced changes seen following hepatectomies were possibly related to the loss of liver tissue.
Background
Preoperative portal vein embolization (PVE) is frequently used to improve future liver remnant volume (FLRV) and to reduce the risk of liver failure after major liver resection.
Objective
...This paper aimed to assess postoperative outcomes after PVE and resection for suspected perihilar cholangiocarcinoma (PHC) in an international, multicentric cohort.
Methods
Patients undergoing resection for suspected PHC across 20 centers worldwide, from the year 2000, were included. Liver failure, biliary leakage, and hemorrhage were classified according to the respective International Study Group of Liver Surgery criteria. Using propensity scoring, two equal cohorts were generated using matching parameters, i.e. age, sex, American Society of Anesthesiologists classification, jaundice, type of biliary drainage, baseline FLRV, resection type, and portal vein resection.
Results
A total of 1667 patients were treated for suspected PHC during the study period. In 298 patients who underwent preoperative PVE, the overall incidence of liver failure and 90-day mortality was 27% and 18%, respectively, as opposed to 14% and 12%, respectively, in patients without PVE (
p
< 0.001 and
p
= 0.005). After propensity score matching, 98 patients were enrolled in each cohort, resulting in similar baseline and operative characteristics. Liver failure was lower in the PVE group (8% vs. 36%,
p
< 0.001), as was biliary leakage (10% vs. 35%,
p
< 0.01), intra-abdominal abscesses (19% vs. 34%,
p
= 0.01), and 90-day mortality (7% vs. 18%,
p
= 0.03).
Conclusion
PVE before major liver resection for PHC is associated with a lower incidence of liver failure, biliary leakage, abscess formation, and mortality. These results demonstrate the importance of PVE as an integral component in the surgical treatment of PHC.
Approximately 30% of patients with colorectal cancer develop colorectal liver metastases (CRLM). CRLM that become undetectable by imaging after chemotherapy are called disappearing liver metastases ...(DLM). But a DLM is not necessarily equal to cure. An increasing incidence of patients with DLM provides surgeons with a difficult dilemma: to resect or to not resect the original sites of DLM? The aim of this review was to investigate to what extent a DLM equates a complete response (CR) and to compare outcomes.
This review was conducted in accordance with the PRISMA guidelines and registered in Prospero (registration number CRD42017070441). Literature search was made in the PubMed and Embase databases. During the process of writing, PubMed was repeatedly searched and reference lists of included studies were screened for additional studies of interest for this review. Results were independently screened by two authors with the Covidence platform. Studies eligible for inclusion were those reporting outcomes of DLM in adult patients undergoing surgery following chemotherapy.
Fifteen studies were included with a total of 2955 patients with CRLM. They had 4742 CRLM altogether. Post-chemotherapy, patients presented with 1561 DLM. Patients with one or more DLM ranged from 7 to 48% (median 19%). Median DLM per patient was 3.4 (range 0.4-5.6). Patients were predominantly evaluated by contrast-enhanced computed tomography (CE-CT) before and after chemotherapy, with some exceptions and with addition of magnetic resonance imaging (MRI) in some studies. Intraoperative ultrasound (IOUS) was universally performed in all but two studies. If a DLM remained undetectable by IOUS, this DLM represented a CR in 24-96% (median 77.5%). Further, if a DLM on preoperative CE-CT remained undetectable by additional workup with MRI and CE-IOUS, this DLM was equal to a CR in 75-94% (median 89%). Patients with resected DLM had a longer disease-free survival compared to patients with DLM left in situ but statistically significant differences in overall survival could not be found.
Combination of CE-CT, MRI, and IOUS showed promising results in accurately identifying DLM with CR. This suggests that leaving DLM in situ could be an alternative to surgical resection when a DLM remains undetectable by MRI and IOUS.
Preoperative prediction of microvascular invasion (MVI) is of importance in hepatocellular carcinoma (HCC) patient treatment management. Plenty of radiomics models for MVI prediction have been ...proposed. This study aimed to elucidate the role of radiomics models in the prediction of MVI and to evaluate their methodological quality. The methodological quality was assessed by the Radiomics Quality Score (RQS), and the risk of bias was evaluated by the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Twenty-two studies using CT, MRI, or PET/CT for MVI prediction were included. All were retrospective studies, and only two had an external validation cohort. The AUC values of the prediction models ranged from 0.69 to 0.94 in the test cohort. Substantial methodological heterogeneity existed, and the methodological quality was low, with an average RQS score of 10 (28% of the total). Most studies demonstrated a low or unclear risk of bias in the domains of QUADAS-2. In conclusion, a radiomics model could be an accurate and effective tool for MVI prediction in HCC patients, although the methodological quality has so far been insufficient. Future prospective studies with an external validation cohort in accordance with a standardized radiomics workflow are expected to supply a reliable model that translates into clinical utilization.
Radical tumor resection (pR0) is prognostic for disease-free and overall survival after resection of perihilar cholangiocarcinoma (pCCA). However, no universal agreement exists on the definition of ...radical resection and histopathological reporting. The aim of this study was to provide a standardized protocol for histopathological assessment and reporting of the surgical specimen obtained after resection for pCCA. All consecutive patients operated for pCCA with curative intent at the Karolinska University Hospital, Stockholm, Sweden between 2012 and 2021 were included. A standardized protocol for histopathological assessment and reporting of the surgical specimen after liver resection for pCCA is presented. A detailed mapping of the transection margins and dissection planes was performed. The results of applying different existing pR0 definitions were compared. Sixty-eight patients with pCCA were included. Five transection margins and two dissection planes were defined. By defining pR0 as cancer-free margins and planes tolerating distances <1mm, the pR0 rate was 66%. However, when pR0 was set as >1mm from invasive cancer to all resection margins and dissection planes, the pR0 rate fell to 16%. This study supports the use of thorough and standardized pathological handling, assessment and reporting of resection margins and dissection planes of surgical specimens of pCCA.
Resections for intraductal papillary mucinous neoplasm (IPMN) have increased last decades. Overall survival (OS) for conventional pancreatic ductal adenocarcinoma (PDAC) is well known but OS for ...invasive IPMN (inv-IPMN) is not as conclusive. This study aims to elucidate potential differences in clinicopathology and OS between these tumor types and to investigate if the raised number of resections have affected outcome.
Consecutive patients ≥18 years of age resected for inv-IPMN and PDAC at Karolinska University Hospital between 2009 and 2018 were included. Clinicopathological variables were analyzed in multivariable regression models. Outcome was assessed calculating two-year OS, estimating OS using the Kaplan-Meier model and comparing survival functions with log-rank test.
513 patients were included, 122 with inv-IPMN and 391 with PDAC. During the study period both the proportion resected inv-IPMN and two-year OS, irrespective of tumor type, increased (2.5%–45%; p < 0.001 and 44%–57%; p = 0.005 respectively). In Kaplan-Meier survival analysis inv-IPMN had more favorable median OS (mOS) compared to PDAC (33.6 months vs 19.3 months, p = 0.001). However, in multivariable Cox Regression analysis, tumor type was not a predictor for death, but so were resection period, tumor subtype and N-stage (all p < 0.001).
In this large single center observational cohort study, inv-IPMN seemed to have favorable survival outcome compared to PDAC, but after adjusting for predictors for death this benefit vanished. The combination of a pronounced increase in resected inv-IPMN and a concurrent hazard abatement for death within 2 years during the study period proved to be a principal factor.
Abstract
A perimetastatic capsule is a strong positive prognostic factor in liver metastases, but its origin remains unclear. Here, we systematically quantify the capsule’s extent and cellular ...composition in 263 patients with colorectal cancer liver metastases to investigate its clinical significance and origin. We show that survival improves proportionally with increasing encapsulation and decreasing tumor-hepatocyte contact. Immunostaining reveals the gradual zonation of the capsule, transitioning from benign-like NGFR
high
stroma at the liver edge to FAP
high
stroma towards the tumor. Encapsulation correlates with decreased tumor viability and preoperative chemotherapy. In mice, chemotherapy and tumor cell ablation induce capsule formation. Our results suggest that encapsulation develops where tumor invasion into the liver plates stalls, representing a reparative process rather than tumor-induced desmoplasia. We propose a model of metastases growth, where the efficient tumor colonization of the liver parenchyma and a reparative liver injury reaction are opposing determinants of metastasis aggressiveness.
PDF
