ICG-Enhanced Compression Anatomical Segment 7 Segmentectomy in Laparoscopic and Robotic Approach.

BACKGROUND: Minimally invasive anatomical resection (AR) for posterosuperior lesions is technically challenging.1,2 The Glissonean approach or puncture technique is generally selected.3,4 The tumor-feeding portal pedicle compression AR (C-AR) is an established procedure in open surgery.5 This technique has benefited from the association with indocyanine green (ICG) fluorescence, used to enhance the anatomical area to be resected.6 Recently, C-AR via the minimal access approach has been reported.7 Herein, we report the first cases of laparoscopic and robotic segment 7 (S7) segmentectomy using the ICG-enhanced compression technique. PATIENTS AND METHODS: Two cases of CHILD-class A hepatocellular carcinoma (HCC) in segment 7 with a liver stiffness less than 7 kPa treated by laparoscopic and robotic anatomical S7 segmentectomies were reported. Using the intraoperative ultrasound (IOUS), the tumor-bearing portal pedicle and the level targeted for compression were identified. The right hemiliver was adequately mobilized to allow handling of the organ during dissection. Using the grasper and the probe itself, the S7 Glissonean pedicle was transparenchymally compressed under real-time IOUS control. To further enhance the visibility of the discolored S7, ICG was administered intravenously, obtaining the compressed area to be resected as a non-stained one. Dissection was performed under intermittent Pringle maneuver up to exposing the right hepatic vein, dividing the Glissonean pedicle to segment 7 and then completing the resection. RESULTS: Pathologic findings demonstrated a 4.9 cm and 7.3 cm HCC with a R0-resection margin (> 1 cm in both). Postoperative complications were nil. The patients were discharged 6 days after surgery. CONCLUSIONS: This preliminary experience shows that the C-AR is a feasible and reliable technique in laparoscopic and robotic approach for posterosuperior lesions. Further studies are needed to investigate its applicability and standardization.

Filamin A is involved in human intrahepatic cholangiocarcinoma aggressiveness and progression.

BACKGROUND & AIMS: Intrahepatic cholangiocarcinoma (iCCA) is a primary liver tumour, characterized by poor prognosis and lack of effective therapy. The cytoskeleton protein Filamin A (FLNA) is involved in cancer progression and metastasis, including primary liver cancer. FLNA is cleaved by calpain, producing a 90 kDa fragment (FLNACT ) that can translocate to the nucleus and inhibit gene transcription. We herein aim to define the role of FLNA and its cleavage in iCCA carcinogenesis. METHODS & RESULTS: We evaluated the expression and localization of FLNA and FLNACT in liver samples from iCCA patients (n = 82) revealing that FLNA expression was independently correlated with disease-free survival. Primary tumour cells isolated from resected iCCA patients expressed both FLNA and FLNACT , and bulk RNA sequencing revealed a significant enrichment of cell proliferation and cell motility pathways in iCCAs with high FLNA expression. Further, we defined the impact of FLNA and FLNACT on the proliferation and migration of primary iCCA cells (n = 3) and HuCCT1 cell line using silencing and Calpeptin, a calpain inhibitor. We observed that FLNA silencing decreased cell proliferation and migration and Calpeptin was able to reduce FLNACT expression in both the HuCCT1 and iCCA cells (p < .05 vs. control). Moreover, Calpeptin 100 µM decreased HuCCT1 and primary iCCA cell proliferation (p <.00001 vs. control) and migration (p < .05 vs. control). CONCLUSIONS: These findings demonstrate that FLNA is involved in human iCCA progression and calpeptin strongly decreased FLNACT expression, reducing cell proliferation and migration.

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.

Mapping Tumor Heterogeneity via Local Entropy Assessment: Making Biomarkers Visible.

Advanced imaging and analysis improve prediction of pathology data and outcomes in several tumors, with entropy-based measures being among the most promising biomarkers. However, entropy is often perceived as statistical data lacking clinical significance. We aimed to generate a voxel-by-voxel visual map of local tumor entropy, thus allowing to (1) make entropy explainable and accessible to clinicians; (2) disclose and quantitively characterize any intra-tumoral entropy heterogeneity; (3) evaluate associations between entropy and pathology data. We analyzed the portal phase of preoperative CT of 20 patients undergoing liver surgery for colorectal metastases. A three-dimensional core kernel (5 × 5 × 5 voxels) was created and used to compute the local entropy value for each voxel of the tumor. The map was encoded with a color palette. We performed two analyses: (a) qualitative assessment of tumors' detectability and pattern of entropy distribution; (b) quantitative analysis of the entropy values distribution. The latter data were compared with standard Hounsfield data as predictors of post-chemotherapy tumor regression grade (TRG). Entropy maps were successfully built for all tumors. Metastases were qualitatively hyper-entropic compared to surrounding parenchyma. In four cases hyper-entropic areas exceeded the tumor margin visible at CT. We identified four "entropic" patterns: homogeneous, inhomogeneous, peripheral rim, and mixed. At quantitative analysis, entropy-derived data (percentiles/mean/median/root mean square) predicted TRG (p < 0.05) better than Hounsfield-derived ones (p = n.s.). We present a standardized imaging technique to visualize tumor heterogeneity built on a voxel-by-voxel entropy assessment. The association of local entropy with pathology data supports its role as a biomarker.

Multimodal single-cell profiling of intrahepatic cholangiocarcinoma defines hyperactivated Tregs as a potential therapeutic target.

BACKGROUND & AIMS: The landscape and function of the immune infiltrate of intrahepatic cholangiocarcinoma (iCCA), a rare, yet aggressive tumor of the biliary tract, remains poorly characterized, limiting development of successful immunotherapies. Herein, we aimed to define the molecular characteristics of tumor-infiltrating leukocytes with a special focus on CD4+ regulatory T cells (Tregs). METHODS: We used high-dimensional single-cell technologies to characterize the T-cell and myeloid compartments of iCCA tissues, comparing these with their tumor-free peritumoral and circulating counterparts. We further used genomics and cellular assays to define the iCCA-specific role of a novel transcription factor, mesenchyme homeobox 1 (MEOX1), in Treg biology. RESULTS: We found poor infiltration of putative tumor-specific CD39+ CD8+ T cells accompanied by abundant infiltration of hyperactivated CD4+ Tregs. Single-cell RNA-sequencing identified an altered network of transcription factors in iCCA-infiltrating compared to peritumoral T cells, suggesting reduced effector functions by tumor-infiltrating CD8+ T cells and enhanced immunosuppression by CD4+ Tregs. Specifically, we found that expression of MEOX1 was highly enriched in tumor-infiltrating Tregs, and demonstrated that MEOX1 overexpression is sufficient to reprogram circulating Tregs to acquire the transcriptional and epigenetic landscape of tumor-infiltrating Tregs. Accordingly, enrichment of the MEOX1-dependent gene program in Tregs was strongly associated with poor prognosis in a large cohort of patients with iCCA. CONCLUSIONS: We observed abundant infiltration of hyperactivated CD4+ Tregs in iCCA tumors along with reduced CD8+ T-cell effector functions. Interfering with hyperactivated Tregs should be explored as an approach to enhance antitumor immunity in iCCA. LAY SUMMARY: Immune cells have the potential to slow or halt the progression of tumors. However, some tumors, such as intrahepatic cholangiocarcinoma, are associated with very limited immune responses (and infiltration of cancer-targeting immune cells). Herein, we show that a specific population of regulatory T cells (a type of immune cell that actually suppresses the immune response) are hyperactivated in intrahepatic cholangiocarcinoma. Targeting these cells could enable cancer-targeting immune cells to act more effectively and should be looked at as a potential therapeutic approach to this aggressive cancer type.

PET/CT-based radiomics of mass-forming intrahepatic cholangiocarcinoma improves prediction of pathology data and survival.

PURPOSE: Intrahepatic cholangiocarcinoma (IHC) is an aggressive disease with few reliable preoperative biomarkers. This study aims to elucidate if radiomics extracted from preoperative [18F]FDG PET/CT may grant a non-invasive biological characterization of IHC and predict outcome after complete resection of the tumor. METHODS: All patients preoperatively imaged by [18F]FDG PET/CT who underwent hepatectomy for mass-forming IHC in the period 2010-2019 were retrospectively evaluated. On PET images, manual slice-by-slice segmentation of IHC was performed (Tumor-VOI). A 5-mm margin region was semi-automatically generated around the tumor (Margin-VOI). Textural analysis was performed using the LifeX software. Analyzed outcomes included tumor grading (G3 vs. G1-2), microvascular invasion (MVI), overall survival (OS), and progression-free survival (PFS). The performances of the combined clinical-radiomic models were compared with those of standard clinical models. RESULTS: Overall, 74 patients (40 females, median age 68 years) were included. Considering tumor grading and MVI, the models combining the clinical data and radiomics of the Tumor-VOI had better performances than the clinical ones (AUC = 0.78 vs. 0.72 for grading; 0.87 vs. 0.78 for MVI). The inclusion into the models of radiomics of the Margin-VOI further improved the prediction of grading (AUC = 0.83), but not of MVI. Considering OS and PFS, the models including the preoperative clinical data and radiomics of the Tumor-VOI and Margin-VOI had better performances than the pure clinical ones (C-index = 0.81 vs. 0.76 for OS; 0.81 vs. 0.72 for PFS) and similar to the models including the pathology and postoperative data (C-index = 0.81 for OS; 0.79 for PFS). No model retained the standard SUV measures. CONCLUSION: The PET-based radiomics of IHC can predict pathology data and allow a reliable preoperative evaluation of prognosis. The radiomics of both the tumoral and peritumoral areas had clinical relevance. The combined clinical-radiomic models outperformed the pure preoperative clinical ones and achieved performances non-inferior to the postoperative models.

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.

Indocyanine Green Compression Technique for Anatomical S8 Dorsal Subsegmentectomy for Hepatocellular Carcinoma.

BACKGROUND: Anatomical resection (AR) is a recommended surgical treatment for hepatocellular carcinoma (HCC), although the conventional procedure (dye injection) for AR is difficult to reproduce.1,2 The tumor-feeding portal pedicle compression technique has been proposed as an easy, reversible, repeatable, and oncologically suitable procedure,3-5 and its only drawback is the sometimes faint discoloration of the compressed area. For enhancing its visibility, indocyanine green (ICG) fluorescence imaging has been introduced. This technique is herein disclosed while performing an anatomical S8 dorsal subsegmentectomy. METHODS: A 66-year-old male was admitted for a 3.7 cm HCC in segment 8 dorsal (S8d) grown in non-alcoholic steatohepatitis. The preoperative liver function was graded as Child-Pugh class A. After adequate liver mobilization, the subsegmental Glissonian pedicle to S8d was identified by intraoperative ultrasound (IOUS) and compressed transparenchymally between the probe and the surgeon's fingertip positioned at the opposed side of the liver. Once IOUS-guided vessel compression had begun, ICG was administered intravenously. The compressed vessel created a non-stained area, which was marked using electrocautery. RESULTS: An anatomical S8d subsegmentectomy using the ICG compression technique was performed. There was no congested area and the right hepatic vein was exposed at the hepatocaval confluence because the resection was conducted in a subsegmental fashion. There was no morbidity and no blood transfusions were necessary. The patient was discharged on day 6 after surgery. CONCLUSIONS: This video shows, for the first time, the finger compression technique successfully implemented by ICG imaging for performing an AR for HCC.

The Liver Tunnel: Intention-to-treat Validation of a New Type of Hepatectomy.

OBJECTIVE: This prospective intention-to-treat validation study evaluated the liver tunnel (LT) technique for patients having ≥1 deep centrally located liver tumor, with or without middle hepatic vein (MHV) invasion. BACKGROUND: Conservative surgery has been proposed for patients with deep liver tumors having complex relationships. LT is one such novel technique. METHODS: Eligible patients were prospectively enrolled for LT. LT relies on tumor-vessel detachment, and the presence of communicating veins if MHV resection is necessary. RESULTS: Twenty consecutive patients met the inclusion criteria: 17 had colorectal liver metastases, 1 had hepatocellular carcinoma, 1 had mass-forming cholangiocarcinoma, and 1 had mixed hepatocellular carcinoma-mass-forming cholangiocarcinoma. Nineteen patients underwent LT. The MHV was resected in 6 patients, always sparing segments 4i and 5. Overall, 180 lesions were removed (median 7; range 1-37): 79 lesions were included in the LT specimen (median 3; range 1-13). There was no in-hospital 90-day mortality. Overall morbidity occurred in 10 (50%) patients: major in 2 (10%). All complications were managed conservatively. After a median 15-month follow-up (range 6-48), 2 instances of cut-edge local recurrences were observed. CONCLUSIONS: This study shows that LT is technically feasible and safe. Further studies are needed for standardizing its use.

Minor Hepatectomies: Focusing a Blurred Picture: Analysis of the Outcome of 4471 Open Resections in Patients Without Cirrhosis.

OBJECTIVE: To elucidate minor hepatectomy (MiH) outcomes. SUMMARY BACKGROUND DATA: Liver surgery has moved toward a parenchyma-sparing approach, favoring MiHs over major resections. MiHs encompass a wide range of procedures. METHODS: We retrospectively evaluated consecutive patients who underwent open liver resections in 17 high-volume centers. EXCLUSION CRITERIA: cirrhosis and associated digestive/biliary resections. Resections were classified as (Brisbane nomenclature): limited resections (LR); (mono)segmentectomies/bisegmentectomies (Segm/Bisegm); right anterior and right posterior sectionectomies (RightAnteriorSect/RightPosteriorSect). Additionally, we defined: complex LRs (ComplexLR = LRs with exposed vessels); postero-superior segmentectomies (PosteroSuperiorSegm = segment (Sg)7, Sg8, and Sg7+Sg8 segmentectomies); and complex core hepatectomies (ComplexCoreHeps = Sg1 segmentectomies and combined resections of Sg4s+Sg8+Sg1). Left lateral sectionectomies (LLSs, n = 442) and right hepatectomies (RHs, n = 1042) were reference standards. Outcomes were adjusted for potential confounders. RESULTS: Four thousand four hundred seventy-one MiHs were analyzed. Compared with RHs, MiHs had lower 90-day mortality (0.5%/2.2%), severe morbidity (8.6%/14.4%), and liver failure rates (2.4%/11.6%, P < 0.001), but similar bile leak rates. LR and LLS had similar outcomes. ComplexLR and Segm/Bisegm of anterolateral segments had higher bile leak rates than LLS rates (OR = 2.35 and OR = 3.24), but similar severe morbidity rates. ComplexCoreHeps had higher bile leak rates than RH rates (OR = 1.94); the severe morbidity rate approached that of RH. PosteroSuperiorSegm, RightAnteriorSect, and RightPosteriorSect had severe morbidity and bile leak rates similar to RH rates. MiHs had low liver failure rates, except RightAnteriorSect (vs LLS OR = 4.02). CONCLUSIONS: MiHs had heterogeneous outcomes. Mortality was low, but MiHs could be stratified according to severe morbidity, bile leak, and liver failure rates. Some MiHs had postoperative outcomes similar to RH.

Assessment of the response of hepatocellular carcinoma to interventional radiology treatments.

According to Barcelona Clinic Liver Cancer (BCLC) guidelines, interventional radiology procedures are valuable treatment options for many hepatocellular carcinomas (HCCs) that are not amenable to resection or transplantation. Accurate assessment of the efficacy of therapies at earlier stages enables completion of treatment, optimal follow-up and to prevent potentially unnecessary treatments, side effects and costly failure. The goal of this review is to summarize and describe the radiological strategies that have been proposed to predict survival and to stratify HCC responses after interventional radiology therapies. New techniques currently in development are also described.

Measurement of Total Liver Volume Using the Energy Expenditure: A New Formula.

BACKGROUND: The assessment of liver volume (LV) is important before surgical resection or transplantation to reduce the risk of hepatic insufficiency. LV is usually measured using computed tomography or with some formulas. The aim of this study was to develop a new dynamic formula to predict LV. METHODS: Using computed tomography, LV was calculated in 101 patients without liver disease. LV was correlated with patient metabolic status, calculated with the Harris-Benedict equation for basal energy expenditure (BEE). Activity energy expenditure (AEE) was also calculated. Using linear regression analysis, a new formula was derived and was compared with Heinmann's, Urata's, Emre's, Vauthey's, Yoshizumi's, Yu's, and Hashimoto's formulas. RESULTS: A new basal formula was established: LV = (0.789 × BEE) + 272. It was found to be the most accurate (R2 = 0.39, p < 0.001). Heinmann's, Emre's, and Vauthey's formulas tend to overestimate LV, while Urata's, Yoshizumi's, Yu's, and Hashimoto's formulas tend to underestimate LV. A new AEE formula was also established: LV = (0.789 × AEE) + 272. CONCLUSIONS: These formulas give a dynamic perspective of LV, which may be influenced by the patient's actual clinical status. Using these formulas, it is possible to estimate an increased value of LV, which may contribute to a reduction in the risk of postoperative hepatic insufficiency.

Aggressive and Multidisciplinary Local Approach to Iterative Recurrences of Colorectal Liver Metastases.

BACKGROUND: Liver resection (LR) of colorectal metastases is associated with high recurrence risk. Aggressive local retreatment is advocated, but further recurrences may occur. Poor is known about presentation, treatment, and outcome of iterative recurrences. METHODS: A series of 323 consecutive patients undergoing first LR in the period 2004-2013 was reviewed. Patients with recurrence were included. Any local treatment (surgery, radiofrequency ablation (RFA) and stereotactic body radiation therapy (SBRT)) was analyzed. If first recurrence (1st Rec) was treated, further recurrences and treatments were considered. RESULTS: Overall, 206 (63.8%) patients had 1st Rec; 105 (51.0%) were treated (72 surgery, 19 RFA, 14 SBRT). Among treated patients, 78.1% had 2nd Rec, 74.4% 3rd Rec, 72.2% 4th Rec. Liver involvement progressively decreased (from 81.6 to 30.8%), and pulmonary one increased (from 23.3 to 53.8%). The proportion of treated patients remained stable (1st Rec = 51%, 2nd Rec = 55%, 3rd Rec = 56.3%, 4th Rec = 69.2%): surgery and RFA decreased (from 35.4 to 23.1%; from 9.2 to 0%) and SBRT increased (from 6.8 to 46.2%). Overall, 105 patients received 205 treatments (133 operations in 80 patients). Surgery had the best local disease control: at 2 years 93.4% versus RFA 56.4% (p = 0.0008) and SBRT 74.0% (p = 0.051). In comparison with chemotherapy, recurrence treatment improved survival after 1st Rec (3-year survival 62.9 vs. 13.4%, p < 0.0001), 2nd Rec (61.3 vs. 22.5%, p < 0.0001), and 3rd Rec (2-year survival 88.9 vs. 30.8%, p = 0.005). CONCLUSIONS: Aggressive local treatment of recurrent metastases may improve survival, even in the case of iterative recurrences and extrahepatic lesions. Surgery is the standard, but a multidisciplinary approach should be adopted to enlarge the pool of treatable patients.

Parenchymal-Sparing Surgery for the Surgical Treatment of Multiple Colorectal Liver Metastases Is a Safer Approach than Major Hepatectomy Not Impairing Patients' Prognosis: A Bi-Institutional Propensity Score-Matched Analysis.

BACKGROUND: The performance of parenchymal-sparing hepatectomy (PSH) versus major hepatectomy (MH) in patients with multiple colorectal liver metastases (CLM) is a matter that is yet debated. We investigated the outcome of patients with multiple CLM undergoing PSH instead of MH. METHODS: Databases at 2 institutions were reviewed. A propensity score-matched analysis was applied. Among 554 patients, 110 undergoing PSH and 110 undergoing MH were matched. They were similar in baseline characteristics, comorbidity, and tumor features. Primary outcomes were short- and long-term outcomes. RESULTS: Morbidity was significantly higher in the MH group, while mortality was not significantly different. There were no differences in free-margins width, but a trend of increased survival was seen in the PSH group with a median advantage of 6 months over the MH group. Among the prognostic factors, the T status (hazard ratio [HR] 2.6; p = 0.001), the N status (HR 2.9; p = 0.001), the timing of CLM diagnosis (HR 2.1; p = 0.002), the tumor number (HR 2.0; p = 0.001), the tumor size (HR 2.2; p = 0.015), and the neo-adjuvant chemotherapy (HR 1.7; p = 0.023) were found to be statistically and independently significant for survival. CONCLUSIONS: PSH conveys advantage over MH in terms of decreased postoperative morbidity, and a trend of survival benefit. PSH should be considered a suitable alternative to MH whenever it is technically feasible.

Positron Emission Tomography-Computed Tomography for Patients with Recurrent Colorectal Liver Metastases: Impact on Restaging and Treatment Planning.

BACKGROUND: The impact of fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) for patients with colorectal liver metastases (CLM) still is debated. Its relevance could be enhanced in the case of recurrent disease. The current study aimed to elucidate the role of PET-CT in restaging and treatment planning for recurrent CLM. METHODS: A series of 352 consecutive patients undergoing their first liver resection for CLM between 2005 and 2014 was reviewed. Of these patients, 224 (63.6 %) had a recurrence. The 107 patients who had received PET-CT at diagnosis of recurrence before chemotherapy were analyzed. CT was available in all cases, and magnetic resonance imaging (MRI) was available in 64 cases. RESULTS: Extrahepatic lesions were found in 59 patients. Liver and lung recurrences were detected with excellent sensitivity by CT/MRI and PET-CT (liver: 100 vs. 96.7 %; lung: 95.8 vs. 95.8 %). In detecting other recurrence sites, PET-CT had higher sensitivity than CT/MRI (91.5 vs. 54.2 %, p < 0.01; lymph nodes: 93.5 vs. 64.5 %, p = 0.011; peritoneum: 80 vs. 20 %, p = 0.023; bones: 87.5 vs. 37.5 %, nonsignificant difference). For 28.8 % (17/59) of the patients, the diagnosis of extrahepatic disease was obtained thanks to PET-CT (39.5 % considering nonpulmonary lesions). PET-CT modified treatment strategy in 16 (14.9 %) patients, excluding from surgery 15 (20.3 %) of 74 patients resectable at CT/MRI. This latter subgroup had a lower survival rate than the patients resectable after PET-CT (2-year survival, 22.7 vs. 77.8 %; p = 0.004), similar to the patients unresectable at CT/MRI (57.6 %). CONCLUSIONS: In the authors' experience, PET-CT has offered a relevant contribution to restaging of recurrent CLM. It disclosed one fourth of extrahepatic lesions and prevented worthless surgery for about 20 % of patients.

Twelve-year experience of "radical but conservative" liver surgery for colorectal metastases: impact on surgical practice and oncologic efficacy.

BACKGROUND: Liver surgery for colorectal metastases (CLM) is moving toward parenchyma-sparing approaches. The authors reported the technical feasibility of parenchyma-sparing hepatectomy for deeply located tumors, but its impact on daily practice and long-term outcomes remain unclear. METHODS: The patients undergoing liver resection (LR) for CLM with vascular contact (first-/second-order pedicle or hepatic vein (HV) trunk) were considered. Those undergoing major hepatectomy were excluded. The authors' technique included tumor-vessel detachment, partial resection of marginally infiltrated HVs, and detection of communicating vessels (CVs) among HVs to preserve outflow after HV resection. RESULTS: Among 169 patients with major vascular contact, parenchyma-sparing LR was feasible in 146 (86%). Twenty-eight SERPS, 13 transversal hepatectomies, 6 mini-mesohepatectomies, and 4 liver tunnels were performed. Sixty-six (45%) patients underwent CLM-vessel detachment, 25 (17%) underwent partial HV resection, and 30 (21%) achieved outflow preservation by CV identification. The mortality and severe morbidity rates were 1.4% and 8.2%, respectively. The 5-year survival rate was 30.7%. The parenchyma-sparing strategy failed in 14 (7%) patients because of recurrence in the spared parenchyma or cut edge; 13 were radically retreated. CONCLUSION: Ultrasound-guided parenchyma-sparing surgery is feasible in most patients with ill-located CLMs. This procedure is safe and achieves adequate oncologic outcomes.

Is Tumor Detachment from Vascular Structures Equivalent to R0 Resection in Surgery for Colorectal Liver Metastases? An Observational Cohort.

BACKGROUND: R0 resection is the standard for colorectal liver metastases (CLMs). Adequacy of R1 resections is debated. Detachment of CLMs from vessels has been proposed to prioritize parenchyma sparing and increase resectability, but outcomes are still to be elucidated. The present study aimed to clarify the outcomes of R1 surgery (margin <1 mm) in patients with CLMs, distinguishing standard R1 resection (parenchymal margin, R1Par) and R1 resection with detachment of CLMs from major intrahepatic vessels (R1Vasc). METHODS: All patients undergoing first resection between 2004 and June 2013 were prospectively considered. R0, R1Par, and R1Vasc were compared in per-patient and per-resection area analyses. RESULTS: The study included 627 resection areas in 226 consecutive patients. Fifty-one (8.1 %) resections in 46 (20.4 %) patients were R1Vasc, and 177 (28.2 %) resections in 107 (47.3 %) patients were R1Par. Thirty-two (5.1 %) surgical margin recurrences occurred in 28 (12.4 %) patients. Local recurrence risk was similar between the R0 and R1Vasc groups (per-patient analysis 5.3 vs. 4.3 %; per-resection area analysis 1.5 vs. 3.9 %, p = n.s.) but increased in the R1Par group (19.6 and 13.6 %, p < 0.05 for both). The R1Par group had a higher rate of hepatic-only recurrences (49.5 vs. 36.1 %, p = 0.042). On multivariate analysis, R1Par was an independent negative prognostic factor of overall survival (p = 0.034, median follow-up 33 months); conversely R1Vasc versus R0 had no significant differences. CONCLUSIONS: R1Par resection is not adequate for CLMs. R1Vasc surgery achieves outcomes equivalent to R0 resection. CLM detachment from intrahepatic vessels can be pursued to increase patient resectability and resection safety (parenchymal sparing).

Diagnosis and Management of Bile Leaks After Hepatectomy: Results of a Prospective Analysis of 475 Hepatectomies.

BACKGROUND: The diagnosis and management of bile leaks after hepatectomy are heterogeneous because there is no agreement on the definition of post-hepatectomy biliary fistula. The aim of this study was to validate our definition and management of biliary fistulas after hepatic resection and to compare our results with those proposed by other authors. METHODS: A prospective series of patients who underwent hepatic resection from 2004 to 2012 were established. Drains were maintained for 7 days, and bilirubin was measured on postoperative days (PODs) 3, 5, and 7. Drains were removed if the bilirubin on POD 7 was less than that on POD 5 and less than 171 µmol/l (10 mg/dl). A statistical analysis of prognostic factors for biliary fistula was performed. RESULTS: Among 475 consecutive patients, 39 (8%) had biliary fistulas. Only 8 (1.7%) patients required postoperative interventions. In comparison with other studies, we observed a higher rate of bile leaks, but at the same time, we observed a lower rate of interventional procedures. The area under the receiver operating characteristic curve on POD 7 had the highest predictive value (0.81; P < 0.001). Pringle maneuvers lasting ≥90 min (OR = 3.4; P < 0.001), extended resections (OR = 6.4; P = 0.007), blood transfusions (OR = 2.4; P = 0.035), and resections including segment I (OR = 1.9; P = 0.033) or segment V (OR = 1.8; P = 0.024) were independently associated with an increased risk of bile leak. CONCLUSIONS: The proposed definition of biliary fistula provides effective recognition of those that are clinically relevant with a reduction of the risk of unrecognized collections and minimal postoperative morbidity. REGISTRATION NUMBER: NCT02056028 ( http://www.clinicaltrials.gov ).