Ho-Seong Han

Feasibility of laparoscopic liver resection for tumors located in the posterosuperior segments of the liver, with a special reference to overcoming current limitations on tumor location

BACKGROUND Laparoscopic liver resection is usually limited to the anterolateral segments of the liver (AL; Segments II, III, V, VI, and the inferior part of IV). We evaluated the feasibility of laparoscopic liver resection in the posterosuperior segments (PS; Segments I, VII, VIII, and the superior part of IV). METHOD We analyzed retrospectively the clinical data of 82 patients who underwent laparoscopic liver resection for tumors from September 2003 to September 2007. Patients were classified into 2 groups according to tumor location: group AL (n=54) and group PS (n=28). RESULTS There was no mortality, reoperation, or major complications. Four (5%) conversions to open procedures were necessary. There were no differences in tumor characteristics, including mean tumor size and number of tumors between 2 groups (P = .427 and .611); however, there was a greater proportion of deeply seated tumors in group PS than group AL (P < .001). The predominant type of resection was a minor liver resection (left lateral sectionectomy, segmentectomy, or tumorectomy) in group AL, and a major liver resection (hemihepatectomy or right posterior sectionectomy) in group PS (P < .001). The median operative time in group PS was greater than that in group AL (320 vs 210 min; P < .001). There were no differences in the conversion rate (P = .113), median blood loss (P = .214), rate of intraoperative transfusion (P = .061), median tumor-free margin (P = .613), median hospital stay (P = .166), and rate of complications (P = .148) between the 2 groups. CONCLUSION Laparoscopic liver resection for tumors located in PS is more difficult than in AL but is feasible in selected patients.

Multidimensional Frailty Score for the Prediction of Postoperative Mortality Risk

IMPORTANCE The number of geriatric patients who undergo surgery has been increasing, but there are insufficient tools to predict postoperative outcomes in the elderly. OBJECTIVE To design a predictive model for adverse outcomes in older surgical patients. DESIGN, SETTING, AND PARTICIPANTS From October 19, 2011, to July 31, 2012, a single tertiary care center enrolled 275 consecutive elderly patients (aged ≥65 years) undergoing intermediate-risk or high-risk elective operations in the Department of Surgery. MAIN OUTCOMES AND MEASURES The primary outcome was the 1-year all-cause mortality rate. The secondary outcomes were postoperative complications (eg, pneumonia, urinary tract infection, delirium, acute pulmonary thromboembolism, and unplanned intensive care unit admission), length of hospital stay, and discharge to nursing facility. RESULTS Twenty-five patients (9.1%) died during the follow-up period (median [interquartile range], 13.3 [11.5-16.1] months), including 4 in-hospital deaths after surgery. Twenty-nine patients (10.5%) experienced at least 1 complication after surgery and 24 (8.7%) were discharged to nursing facilities. Malignant disease and low serum albumin levels were more common in the patients who died. Among the geriatric assessment domains, Charlson Comorbidity Index, dependence in activities of daily living, dependence in instrumental activities of daily living, dementia, risk of delirium, short midarm circumference, and malnutrition were associated with increased mortality rates. A multidimensional frailty score model composed of the above items predicted all-cause mortality rates more accurately than the American Society of Anesthesiologists classification (area under the receiver operating characteristic curve, 0.821 vs 0.647; P = .01). The sensitivity and specificity for predicting all-cause mortality rates were 84.0% and 69.2%, respectively, according to the models cutoff point (>5 vs ≤5). High-risk patients (multidimensional frailty score >5) showed increased postoperative mortality risk (hazard ratio, 9.01; 95% CI, 2.15-37.78; P = .003) and longer hospital stays after surgery (median [interquartile range], 9 [5-15] vs 6 [3-9] days; P < .001). CONCLUSIONS AND RELEVANCE The multidimensional frailty score based on comprehensive geriatric assessment is more useful than conventional methods for predicting outcomes in geriatric patients undergoing surgery.

Mesenchymal stem cells showed the highest potential for the regeneration of injured liver tissue compared with other subpopulations of the bone marrow

We have previously reported that bone marrow cells (BMCs) participate in the regeneration after liver injury. However, it is not established that this is the result of differentiation of hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs) or the combination of both. We investigated the contribution of each cell fraction to the regenerative process. First, we confirmed that transplanted stem cells migrate directly to injured liver tissue without dispersing to other organs. Next, we divided green fluorescent protein (GFP)‐expressing BMCs into three populations as mononuclear cells, MSCs and HSCs. We then compared the engraftment capacity after transplantation of each fraction of cells into liver‐injured mice. Of these, the MSCs transplanted group showed the highest GFP fluorescence intensities in liver tissue by flow cytometry analysis and confocal microscopic observation. Furthermore, MSCs showed differentiation potential into hepatocytes when co‐cultured with injured liver cells, which suggests that MSCs showed highest potential for the regeneration of injured liver tissue compared with those of the other two cell refractions.

Outcomes of Laparoscopic Liver Resection for Lesions Located in the Right Side of the Liver

HYPOTHESIS Laparoscopic right-sided liver resection may be feasible and safe. DESIGN Retrospective analysis. SETTING Department of surgery at a university hospital. PATIENTS Of 103 consecutive laparoscopic liver resections performed from May 1, 2003, to April 30, 2007, 46 patients underwent a right-sided laparoscopic liver resection. Six operations required conversion (13%) to open surgery. Overall, data from 40 patients with benign liver tumors (n = 2), intrahepatic duct stones (n = 3), liver metastasis from colorectal cancer (n = 8), and hepatocellular carcinomas (n = 27) were analyzed. MAIN OUTCOME MEASURES Feasibility and operative outcome. RESULTS The operations included 12 major resections (5 right hemihepatectomy and 7 right posterior sectionectomy) and 28 minor resections (14 segmentectomy and 14 tumorectomy). No operative mortality, subsequent operation, or life-threatening complications occurred. Overall, 11 patients (28%) experienced complications; 2 had bile leakage, 6 had perihepatic fluid collection, 2 had prolonged ascites, and 1 had pleural effusion. All recovered after conservative management. The mean operation time was 300 minutes, the mean blood loss was 620 mL, and the mean hospital stay was 11 days. For lesions located at segment VII or VIII (n = 15), the mean operation time and amount of blood loss in those receiving a minor liver resection were similar to those who received a major resection (P = .21 and .88, respectively). CONCLUSION Although greater technical refinement is required for a minor resection in the superior part of the right side of the liver, laparoscopic right-sided liver resection is feasible and safe.

Laparoscopic versus open liver resection for hepatocellular carcinoma: Case-matched study with propensity score matching

BACKGROUND & AIMS Laparoscopic liver resection has gained wide acceptance and is established as a safe alternative to open liver resection. Until now, there is no prospective randomized comparative study between laparoscopic and open liver resection. Previous comparative studies reported minor resections for peripheral tumors, and enrolled small numbers of patients. Moreover, few reported the long term outcomes. The aim of this study is to compare perioperative and long term outcomes of laparoscopic versus open liver resection for hepatocellular carcinoma between two matched groups. METHODS 389 patients underwent liver resection for hepatocellular carcinoma during the period between 2004 and 2013. To overcome selection bias, we performed 1:1 match using propensity score matching between laparoscopic and open liver resection. RESULTS After propensity score matching, 88 patients were included in each group. Laparoscopic group had shorter hospital stay (8 vs. 10 days, p⩽0.001), and lower postoperative morbidity (12.5% vs. 20.4%, p=0.042). The 1-, 3- and 5-year overall survivals were 91.6%, 87.5%, and 76.4%, for laparoscopic group, and were 93.1%, 87.8%, and 73.2%, for open group (p=0.944). The 1-, 3- and 5-year disease free survivals were 69.7%, 52%, and 44.2%, for laparoscopic group, and 74.7%, 49.5%, 41.2%, for open group (p=0.944). CONCLUSIONS Our study showed comparative perioperative and long term outcomes between both groups, providing evidence regarding the safety and efficacy of laparoscopic liver resection for hepatocellular carcinoma.

Techniques for performing laparoscopic liver resection in various hepatic locations

Many studies have recently reported on laparoscopic liver resection, although its development has been slow compared to laparoscopy in other fields. The indications for the location of laparoscopic liver resection have previously been limited to easily accessible lesions. Performing laparoscopic liver resection in the posterior and superior parts of the liver has been considered difficult due to inadequate exposure, the poor operative field and the difficulty with parenchymal dissection. Flexible endoscopy, high definition imaging and various kinds of equipment for parenchymal transection have been introduced for clinical use. In addition, much experience with this procedure has been accumulated at many centers. Accordingly, there are an increasing number of reports on laparoscopic liver resection in difficult locations. At our institution, the location of the tumor is no longer a limitation to laparoscopic liver resection. However, for safer laparoscopic liver resection, the patient positioning and trocar placement should be individualized according to the tumor location. The type of resection also may depend on the remaining livers functional capacity. We describe here the technical considerations for performing laparoscopic liver resection, including the technical considerations for performing laparoscopic liver resection for lesions located in the postero-superior segments of the liver.

Laparoscopic hepatectomy is theoretically better than open hepatectomy: preparing for the 2nd International Consensus Conference on Laparoscopic Liver Resection

Six years have passed since the first International Consensus Conference on Laparoscopic Liver Resection was held. This comparatively new surgical technique has evolved since then and is rapidly being adopted worldwide. We compared the theoretical differences between open and laparoscopic liver resection, using right hepatectomy as an example. We also searched the Cochrane Library using the keyword “laparoscopic liver resection.” The papers retrieved through the search were reviewed, categorized, and applied to the clinical questions that will be discussed at the 2nd Consensus Conference. The laparoscopic hepatectomy procedure is more difficult to master than the open hepatectomy procedure because of the movement restrictions imposed upon us when we operate from outside the body cavity. However, good visibility of the operative field around the liver, which is located beneath the costal arch, and the magnifying provide for neat transection of the hepatic parenchyma. Another theoretical advantage is that pneumoperitoneum pressure reduces hemorrhage from the hepatic vein. The literature search turned up 67 papers, 23 of which we excluded, leaving only 44. Two randomized controlled trials (RCTs) are underway, but their results are yet to be published. Most of the studies (n = 15) concerned short‐term results, with some addressing long‐term results (n = 7), cost (n = 6), energy devices (n = 4), and so on. Laparoscopic hepatectomy is theoretically superior to open hepatectomy in terms of good visibility of the operative field due to the magnifying effect and reduced hemorrhage from the hepatic vein due to pneumoperitoneum pressure. However, there is as yet no evidence from previous studies to back this up in terms of short‐term and long‐term results. The 2nd International Consensus Conference on Laparoscopic Liver Resection will arrive at a consensus on the basis of the best available evidence, with video presentations focusing on surgical techniques and the publication of guidelines for the standardization of procedures based on the experience of experts.

Laparoscopic liver resection for centrally located tumors close to the hilum, major hepatic veins, or inferior vena cava

BACKGROUND Despite the accumulation of favorable results from laparoscopic liver resection (LLR), centrally located tumors close to the hilum, major hepatic veins, or inferior vena cava (IVC) are still considered contraindications for LLR. We evaluated the feasibility and safety of LLR for centrally located tumors. METHODS Of the 182 patients who underwent LLR for benign or malignant tumors between September 2003 and June 2010, the clinical outcomes of 13 patients with tumors within 1 cm or less of the major vascular structures, including the hilum, major hepatic veins, and IVC, were retrospectively analyzed. The perioperative outcomes of the patients were compared with those of the 23 patients who underwent open liver resection for tumors with similar criteria in terms of location and size during the same period. RESULTS Anatomic liver resection, including left and right hepatectomy, central bisectionectomy, right anterior and posterior sectionectomy, and extended S4 segementectomy, was performed in 10 patients. The remaining 3 patients underwent subsegmentectomy for tumors located in the Spiegel lobe of the caudate. There was no open conversion or postoperative mortality. Compared with the open group, the laparoscopic group showed similar rates of intraoperative transfusion, postoperative complications, and operative time. However, the laparoscopic group spent less time in the hospital postoperatively and had shorter resection margins. After a median follow-up of 34.3 months, there were no statistically significant differences between the 2 groups in reference to the overall survival rates and the disease-free survival rates. CONCLUSION This study shows that LLR can be safely performed in selected patients with centrally located tumors close to the liver hilum, the major hepatic veins, or the IVC that were previously considered to be contraindications for LLR. Recent technical developments in the performance of laparoscopic major liver resection may have contributed to the successful application of LLR for centrally located tumors.

Laparoscopic Approach for Suspected Early-Stage Gallbladder Carcinoma

OBJECTIVE To determine the feasibility of the laparoscopic approach for treating suspected early-stage gallbladder carcinoma. DESIGN, SETTING, AND PATIENTS Prospective study from a university hospital. From May 10, 2004, to October 9, 2007, the laparoscopic approach was considered for treating 36 patients with suspected gallbladder carcinoma at T2 or less without liver invasion based on the preoperative computed tomographic scan. To further exclude liver invasion, preoperative endoscopic ultrasonography (US) and laparoscopic US were additionally performed. Frozen biopsy was performed after completing the cholecystectomy. If carcinoma was found, laparoscopic lymphadenectomy was performed. MAIN OUTCOME MEASURES Feasibility and operative outcome. RESULTS Three patients who had liver invasion on endoscopic US underwent open surgery. An additional 3 patients who had liver invasion noted on laparoscopic US had their surgical procedure converted to laparotomy. Finally, 30 patients underwent a laparoscopic procedure. With combined computed tomography, endoscopic US, and laparoscopic US, the negative predictive value for excluding hepatic invasion reached 100%. For the 12 patients who had benign lesions noted on their frozen biopsies, their laparoscopic surgical procedure was completed. The remaining 18 patients who had gallbladder carcinoma underwent additional laparoscopic lymphadenectomy. During laparoscopic lymphadenectomy 1 conversion occurred owing to bleeding, the median operative time was 190 minutes, and the median blood loss was 50 mL. The complication rate was 16.7% and the median postoperative hospital stay was 4 days. After a median follow-up of 27 months, all 18 patients who underwent laparoscopic lymphadenectomy survived without any evidence of recurrence or metastasis. CONCLUSION Laparoscopic treatment is feasible and safe in selected patients with early-stage gallbladder carcinoma.

Multicenter Phase II Study of Sequential Radioembolization-Sorafenib Therapy for Inoperable Hepatocellular Carcinoma

Background The safety and tolerability of sequential radioembolization-sorafenib therapy is unknown. An open-label, single arm, investigator-initiated Phase II study (NCT0071279) was conducted at four Asia-Pacific centers to evaluate the safety and efficacy of sequential radioembolization-sorafenib in patients with hepatocellular carcinoma (HCC) not amenable to curative therapies. Methods Sorafenib (400 mg twice-daily) was initiated 14 days post-radioembolization with yttrium-90 (90Y) resin microspheres given as a single procedure. The primary endpoints were safety and tolerability and best overall response rate (ORR) using RECIST v1.0.Secondary endpoints included: disease control rate (complete [CR] plus partial responses [PR] and stable disease [SD]) and overall survival (OS). Results Twenty-nine patients with Barcelona Clinic Liver Cancer (BCLC) stage B (38%) or C (62%) HCC received a median of 3.0 GBq (interquartile range, 1.0) 90Y-microspheres followed by sorafenib (median dose/day, 600.0 mg; median duration, 4.1 months). Twenty eight patients experienced ≥1 toxicity; 15 (52%) grade ≥3. Best ORR was 25%, including 2 (7%) CR and 5 (18%) PR, and 15 (54%) SD. Disease control was 100% and 65% in BCLC stage B and C, respectively. Two patients (7%) had sufficient response to enable radical therapy. Median survivals for BCLC stage B and C were 20.3 and 8.6 months, respectively. Conclusions This study shows the potential efficacy and manageable toxicity of sequential radioembolization-sorafenib. Trial Registration ClinicalTrials.gov NCT00712790.