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Background: The aim of this study was to evaluate whether 3-dimensional (3D) simulation software is applicable to and useful for anatomic liver segmentectomy and subsegmentectomy., Methods: A prospective study of 83 consecutive patients who underwent anatomic segmentectomy or subsegmentectomy using the puncture method was performed. All patients underwent 3D simulation analysis (SA) preoperatively for planning operative procedures. The clinical information acquired by 3D SA and the consistency of virtual and real hepatectomy were evaluated., Results: The time needed for completing 3D SA was 18.3 ± .7 minutes. Three-dimensional SA proposed resection of multiple segments or subsegments in 29 patients (35%). It also helped complement the resection line in 26 patients (31%) who lacked a bold staining area on the liver surface. The volume of segment or subsegment calculated by 3D SA was correlated with the actual resected specimen (R(2) = .9942, P < .01). The bordering hepatic veins were clearly exposed in 71 patients (86%), in accordance with completed drawings by 3D SA., Conclusions: Three-dimensional SA showed accurate completed drawings and assisted liver surgeons in planning and executing anatomic segmentectomy and subsegmentectomy., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Preoperative chemotherapy containing oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) causes histological liver injury and increases postoperative morbidity and mortality in patients with colorectal liver metastasis (CRLM). However, information on the aggravation of liver function and its reversibility is scarce., Methods: A total of 55 patients who underwent a hepatectomy after receiving FOLFOX and/or FOLFIRI were included in the present study. Indocyanine green tests were repeatedly performed before hepatectomy for monitoring the change of hepatic functional reserve., Results: A significant decrement in the ICG R15 value was observed at 2-4 weeks (12.9%, P = .04), 4-8 weeks (11.4%, P = .01), and 8 or more weeks (11.1%, P = .006) after the last chemotherapy, compared with results documented within 2 weeks (16.8%). However, no significant change was observed among the values obtained at 2-4 weeks, 4-8 weeks, and 8 or more weeks. The individual ICG R15 values at the beginning and end of the cessation period also improved from 17.7% to 11.6% (P = .001). Histological liver injury was associated with larger amounts of operative blood loss but not with morbidity. Neither liver failure nor mortality occurred in the present series., Conclusions: The hepatic functional reserve, represented by the ICG R15 value, improves during the period after chemotherapy cessation. The present study suggests that chemotherapy cessation for at least 2-4 weeks enables an improvement in the hepatic functional reserve, especially among patients with an abnormal ICG R15 value (> 10%) who have received 6 or more cycles of FOLFOX and/or FOLFIRI.

Background: Resection remains the gold standard in the treatment of liver tumors. But radiofrequency ablation allows destruction of small liver tumors. The aim of this study was to evaluate the effect of surface application of a saline-linked dissecting sealer (TL) on the tumor bed that might contain residual microscopic tumor cells after resection (in situ margin)., Study Design: Five hepatitis-infected woodchucks bearing primary liver tumors were used. Tumors > 1 cm in diameter were removed by tumorectomy. Alternately, the in situ margins were treated or not by TL. All samples were frozen and stained with hematoxylin and eosin and nicotine adenine dinucleotide (cell viability test). The median tumor diameter was 22 mm (range 10 to 53 mm). Among 84 in situ retrieved samples, 50 were from TL-treated tumors and 34 were from untreated controls., Results: The mean (+/-SD) heat-zone area was 12.6+/-2.8 mm in TL-treated tumors and 0.6+/-0.7 mm in controls (p < 0.001). Hematoxylin and eosin and nicotine adenine dinucleotide analyses showed 70% to 98% of cell destruction inside the heat-zone area in the TL-treated samples. There were macroscopic residual tumor cells (R2 resection) in 53 samples, with a median length of tumoral tissue inside the in situ margin of 3.5 mm. Among them, the heat-zone area was considerably longer in TL-treated versus untreated controls (13.3+/-2.6 mm versus 0.7+/-0.9 mm, p < 0.001). In samples with no residual tumor cells or microscopic residual tumor cells (R0/R1; n=31), the length of the tumoral margin was similar between TL-treated and untreated controls (0.7+/-0.2 mm and 0.9+/-0.2 mm, respectively, p=NS). Compared with controls, no viable cell was visible (up to 5 mm of depth) in the in situ margins in the TL-treated samples (p < 0.05)., Conclusions: These results support the hypothesis that surface application of the TL device on the in situ margins after tumorectomy could induce a substantial heat-zone area ranging from 10 to 13 mm, inside which, on a regressive heat gradient, up to 98% of cells could be destroyed. These observations could help to reduce marginal recurrence, especially in patients requiring multiple tumorectomies or complex liver resections for malignancy.

Objective: To establish the indications of the liver hanging maneuver for major hepatectomy., Summary Background Data: The liver hanging maneuver, which is a technique of passing a tape along the retrohepatic avascular space and suspending the liver during parenchymal transection, facilitates anterior approach of major hepatectomy. However, the feasibility and limits of this maneuver have never been established in patients with different clinical backgrounds., Methods: Medical records of 242 consecutive patients considered for major hepatectomy using the hanging maneuver were reviewed., Results: Among 242 patients, 14 patients (6%) were considered to have contraindication for this maneuver preoperatively because of tumor infiltration to anterior surface of retrohepatic inferior vena cava (IVC). It was successful in 201 patients with overall feasibility of 88%. The feasibility increased significantly in the recent years as compared with the initial years (94% in 2003-2005 vs. 76% in 2000-2002, P < 0.0001). Bleeding during the retrohepatic dissection occurred in 5 patients (2%), which was minor due to injury of hepatic capsule in 3 (1%) and major due to injury of short hepatic vein in 2 (1%). In all cases, bleeding stopped spontaneously. The maneuver was abandoned in 27 patients, including 15 related to severe adhesion between liver and IVC. Univariate analysis showed that adhesion between IVC and liver was the only significant negative predictor affecting the feasibility. Cirrhosis, large tumor, preoperative radiologic treatments did not influence on the feasibility., Conclusions: The liver hanging maneuver has 94% feasibility in recent years. Absolute contraindication is tumor infiltration to the retrohepatic avascular space. Adhesion between the IVC and liver has a negative impact of the feasibility. According to this indication, the hanging maneuver is easily achievable without risk of the major bleeding during the retrohepatic dissection.

Complete resection of colorectal liver metastases (LM) has been the only curative treatment. However, when LM are multiple and bilobar, only a few patients are candidates for curative surgery. We report on a 53-year-old woman with synchronous multiple and bilobar LM from sigmoidal cancer who became resectable after a multimodal strategy including preoperative systemic chemotherapy and two-step surgery. The spectacular decrease in tumor size after systemic chemotherapy led us to perform two-step surgery, including right portal-vein ligation and left liver metastasectomies, with a coupled saline-radiofrequency device, in order to improve the surgical margin. An extended right hepatectomy was performed later to remove the remaining right liver lesions. The patient was discharged after 28 days without major complication and was recurrence-free 14 months later. We conclude that improving the surgical margin with a coupled saline-radiofrequency device is feasible and effective, avoiding small remnant liver even after multiple tumorectomies. The multimodal strategy, including preoperative chemotherapy, two-step surgery, and tumorectomies, using a coupled saline-radiofrequency device, could increase the number of patients with diffuse bilobar liver metastases who can benefit from liver resection.

The main goal of liver resection in patients with liver tumor is to cure the patients with the lowest operative risk. Based on our experiences, we report herein, indications of liver resection according to the nature of underlying liver parenchyma. In patients with normal underlying liver parenchyma, major resection does not require specific preoperative assessment. Non-tumorous biopsy is indicated in cases of massive steatosis and/or in patients in whom a complex technical procedure is anticipated. Portal vein embolization (PVE) is considered if the future liver remnant (FLR) is < 30%. In patients with chronic liver disease, major hepatectomy is a risky situation, requiring specific preoperative assessment, including non-tumorous biopsy and PVE which could be associated with transarterial chemoembolization. Absence of hypertrophy of the FLR after PVE is a contraindication to a major hepatectomy. Intraoperative procedures in patients "at risk" require specific techniques, including intermittent clamping, anterior approach with hanging maneuver, and fixation on anatomical position of the remnant liver.

Objective: To evaluate the efficacy of a novel 2-stage treatment with reductive surgery plus percutaneous isolated hepatic perfusion (PIHP) for multiple hepatocellular carcinoma (HCC), which was previously unresectable., Summary Background Data: Surgical resection is the treatment of choice for HCC, but the majority of patients with advanced HCC are not suitable candidates. PIHP is a minimally invasive surgery that allows high-dose regional chemotherapy of the liver, and our phase II studies have shown its profound efficacy for the local control of advanced HCC., Methods: Twenty-five patients with multiple advanced HCC were enrolled in this prospective study. In the first stage, all patients underwent reductive hepatectomy: major hepatectomy in 13 patients and segmentectomy or less in 12. In 2 patients with subsegmentectomy, the retropancreatic and periportal metastatic lymph nodes were synchronously resected. Regardless of the type of hepatectomy, all patients routinely underwent cholecystectomy, and ligations of the right gastric artery and arterial collaterals of the remnant liver to increase the safety and efficacy of PIHP. In the second stage, PIHP with doxorubicin 60-120 mg/m2/treatment was planned for a period of 1 to 3 months after surgery., Results: Of 25 enrolled patients, 22 successfully underwent PIHP an average of 1.8 times for the local control of residual liver tumors. In the remaining 3 patients, PIHP was abandoned because 2 had rapid disease progression and 1 had liver failure after surgery. In 22 patients with the 2-stage treatment, 19 (86%) had objective local tumor control (10 complete remissions and 9 partial responses with a median response duration of 16 months). The actuarial survival rate of all 25 patients was 42% at 5 years., Conclusions: Reductive surgery plus PIHP produced a strong antitumoral effect on multiple advanced HCC, when liver function allows this concentrated treatment approach, and offers long-term survival in a subset of patients who were previously deemed to have unresectable disease.

The NS3 protein of hepatitis C virus subtype 1b (HCV-1b) isolates obtained from 89 patients with hepatocellular carcinoma (HCC) and 78 patients without HCC were analyzed. On the basis of the secondary structure of the amino-terminal 120 residues of NS3, HCV-1b isolates were classified into group A, group B, and an indeterminate group, each of which was further divided into a number of subgroups, such as A1-1, A1-2, A2-1, A2-2, B1-1, B1-2, B2-1, B2-2, C-1, C-2, and C-3. HCV-1b isolates of subgroup B1-1 were found in 53 (59.6%) of 89 patients with HCC and 19 (24.4%) of 78 patients without HCC, with the difference between the two patient groups being statistically significant (P < 0.00001). Although the number of isolates was small, subgroup B2-1 was also highly associated with HCC, with all five isolates in that subgroup being found in patients with HCC (P < 0.05). On the other hand, HCV-1b isolates of subgroup A1-1 were associated only weakly with HCC; they were found in 6 (6.7%) of 89 patients with HCC and in 25 (32.1%) of 78 patients without HCC, with the difference between the two patient groups being statistically significant (P < 0.0001). The other subgroups, such as A1-2, A2-1, B1-2, C-1, C-2, and C-3, were moderately associated with HCC; their distribution patterns among patients with HCC did not differ significantly from those among patients without HCC. Taken together, our results suggest that HCV-1b isolates of subgroups B1-1 and B2-1 are highly associated with HCC and that this secondary structure analysis may be useful for predicting the relative risk of developing HCC.

The core protein of hepatitis C virus (HCV) has been implicated in hepatocarcinogenesis. In order to determine whether there is a correlation between mutations of the core protein and the development of hepatocellular carcinoma (HCC), the core protein-coding sequence of the viral genome of HCV subtype 1b (HCV-1b) obtained from patients with and without HCC was analyzed. We found that 12 (40.0%) of 30 HCV-1b isolates from patients with HCC but none of 29 isolates from patients without HCC had a point mutation(s) in an N-terminal region of 20 residues. Similarly, 10 (33.3%) of 30 isolates from patients with HCC had mutations in a limited region between residues 141 and 160, whereas only 2 (6.9%) of 29 isolates from patients without HCC did. The differences between the two groups were statistically significant. The mutations were found in isolates from both cancerous and adjacent noncancerous tissues of patients with HCC, suggesting that the mutations were present before the development of HCC. The other regions of the core protein of some isolates also had mutations, but no significant difference was observed between isolates from patients with HCC and those from patients without HCC. The F protein, a frameshift product that is still hypothetical for HCV-1b strains, showed more sequence diversity than the core protein among the isolates analyzed, but there were no significant differences in the mutation rates or positions between isolates from patients with HCC and isolates from patients without HCC, except for a short N-terminal sequence of approximately 11 residues that is shared with the core protein.