Michiro Takahashi

Neither Multiple Tumors Nor Portal Hypertension Are Surgical Contraindications for Hepatocellular Carcinoma

BACKGROUND & AIMS The surgical indications for multiple hepatocellular carcinomas (HCCs) and for HCC with portal hypertension (PHT) remain controversial. METHODS We reviewed 434 patients who had undergone an initial resection for HCC and divided them into a multiple (n = 126) or single (n = 308) group according to the number of tumors. We also classified 386 of the patients into a PHT group (n = 136) and a no-PHT (n = 250) group according to whether they had PHT (defined by the presence of esophageal varices or a platelet count of <100,000/microL in association with splenomegaly). RESULTS Among Child-Pugh class A patients, the overall survival rates in the multiple group were 58% at 5 years, and 56% in the PHT group, which were lower than those in the single group (68%, P = .035) and the no-PHT group (71%, P = .008). Among Child-Pugh class B patients with multiple HCCs, the 5-year overall survival rate was 19%. Multivariate analyses revealed that the presence of multiple tumors was an independent risk factor for postoperative recurrence (relative risk, 1.64; 95% confidence interval, 1.23-2.18; P = .001). A second resection resulted in satisfactory overall survival after the diagnosis of recurrence in the multiple (73% at 3 years) or PHT (73%) groups, as well as in the single (79%) or no PHT (81%) groups. CONCLUSIONS Resection can provide survival benefits even for patients with multiple tumors in a background of Child-Pugh class A cirrhosis, as well as in those with PHT.

Pancreatoduodenectomy With Systematic Mesopancreas Dissection Using a Supracolic Anterior Artery-first Approach.

Objective: To describe the details of the surgical technique of pancreatoduodenectomy (PD) with systematic mesopancreas dissection (SMD-PD), using a supracolic anterior artery-first approach. Background: An artery-first approach in PD has been advocated in pancreatic cancer to judge resectability, clear the superior mesenteric artery margin from invasion, or reduce blood loss. However, the efficacy of an artery-first approach in mesopancreas dissection remains unclear. Methods: This study involved 162 consecutive patients who underwent PD with curative intent. The patients were divided into 82 SMD-PDs and 80 conventional PDs (CoPD) and then stratified further according to the dissection level, that is, level 1 was applied to 24 simple mesopancreas divisions for early inflow occlusion including 11 SMD-PDs, level 2 for 63 en bloc mesopancreas resections (26 SMD-PDs), and level 3 for 75 patients who underwent a hemicircumferential superior mesenteric artery plexus resection to keep the margin free from cancer invasion (45 SMD-PDs). The clinical and imaging results were collected to assess the feasibility and validity of SMD-PD with an artery-first approach. Results: Blood loss and operation duration were significantly less in the SMD-PD group than in the CoPD group among the total 162 patients. The imaging analysis showed that four fifths of pancreatic arterial branches came from the right dorsal aspect of the superior mesenteric artery and cancer abutment occurred exclusively from the same direction indicating the validity of an artery-first approach. Conclusions: SMD-PD using an SAA is feasible across PD cases, with acceptable short-term outcomes, and we propose this procedure as a promising option for PD.

Usefulness of contrast-enhanced intraoperative ultrasound using Sonazoid in patients with hepatocellular carcinoma.

Objective:To assess the usefulness of contrast-enhanced intraoperative ultrasound (CE-IOUS) using Sonazoid (gaseous perflubutane) in patients with hepatocellular carcinoma (HCC). Background:Contrast-enhanced intraoperative ultrasound using Sonazoid, a novel ultrasonic contrast agent enabling Kupffer imaging, may enable differentiation of HCC among new focal liver lesions found during fundamental intraoperative ultrasound (fundamental-NFLLs). Methods:Between February 2007 and February 2009, a total of 192 consecutive patients were enrolled. Fundamental intraoperative ultrasound and CE-IOUS were performed successively after laparotomy. The vascularity of 1 representative lesion was examined in harmonic mode for approximately 1 minute after the intravenous injection of Sonazoid (vascular phase). Approximately 15 minutes after the vascular phase, total liver scanning in the harmonic mode was commenced (Kupffer phase). One additional injection of Sonazoid was allowed to examine the vascularity of another lesion, if necessary. A tentative diagnosis of HCC was made when a lesion was either hypervascular during the vascular phase or hypoechoic during the Kupffer phase. A final diagnosis of HCC was made on the basis of the results of a histological examination or dynamic computed tomography findings obtained during the 12-month postoperative period. Results:Seventy-nine fundamental-NFLLs were found in 50 patients (26%), 17 (22%) of which were finally diagnosed as HCC. The sensitivity, specificity, and accuracy of CE-IOUS for differentiating HCC among fundamental-NFLLs were 65%, 94%, and 87%, respectively. Contrast-enhanced intraoperative ultrasound identified 21 additional new hypoechoic lesions in 16 patients, of which 14 lesions (67%) in 11 patients were finally diagnosed as HCC. This prospective study protocol was approved by the institutional review board of the Tokyo University Hospital. An English-language summary of the protocol was submitted (registration ID: UMIN000003046) to the Clinical Trials Registry managed by the University Hospital Medical Information Network in Japan (http://www.umin.ac.jp/ctr/index.htm). Conclusions:With help of CE-IOUS using Sonazoid, more accurate intraoperative staging for HCC can be performed.

Contrast-enhanced intraoperative ultrasonography using perfluorobutane microbubbles for the enumeration of colorectal liver metastases.

Intraoperative ultrasonography (IOUS) is considered the standard for the identification of liver metastases. Use of lipid‐stabilized perfluorobutane microbubbles as an ultrasound contrast agent may improve this. The value of contrast‐enhanced IOUS (CE‐IOUS) in enumerating colorectal liver metastases was studied here.

Correlation Between Contrast-Enhanced Intraoperative Ultrasound Using Sonazoid and Histologic Grade of Resected Hepatocellular Carcinoma

OBJECTIVE Our aim was to accurately assess the correlation between findings of contrast-enhanced intraoperative ultrasound using Sonazoid and histologic grade of hepatocellular carcinoma (HCC). SUBJECTS AND METHODS We enrolled 239 consecutive patients who were undergoing surgery for HCC for this study. Because 33 extensively necrotic HCCs were excluded, a total of 374 histologically proven HCCs were detected in all resected specimens and were the study subjects (71 well-differentiated, 239 moderately differentiated, and 64 poorly differentiated HCCs). After a laparotomy and liver mobilization, contrast-enhanced intraoperative ultrasound in the harmonic mode was performed after a Sonazoid injection. The first minute was defined as the vascular phase, in which the vascularity of the 239 HCCs was assessed. After an approximately 15-minute delay, a thorough liver exploration was performed (Kupffer phase). Preoperative dynamic CT was routinely performed, and the findings were assessed for reference. RESULTS The proportion of hypervascular tumors during the vascular phase tended to be lower among well-differentiated than among moderately and poorly differentiated HCCs (66% vs 80%, p = 0.058). The proportion of hypoechoic tumors during the Kupffer phase was significantly lower among well-differentiated than among moderately and poorly differentiated HCCs (54% vs 92%, p < 0.0001). In dynamic CT, the proportions of hypervascular tumors during the early phase and hypodense tumors during the late phase were significantly lower among well-differentiated HCCs than among moderately and poorly differentiated HCCs, respectively (early phase, 51% vs 87%, p < 0.0001; late phase, 59% vs 85%, p < 0.0001). CONCLUSION Contrast-enhanced intraoperative ultrasound using Sonazoid is useful for estimating the histologic grade of HCC.

Anatomical Liver Resections Guided by 3-Dimensional Parenchymal Staining Using Fusion Indocyanine Green Fluorescence Imaging.

OBJECTIVE To investigate the feasibility and efficacy of anatomical liver resection (ALR) guided by fused images comprising a macroscopic view and indocyanine green fluorescence imaging (fusion IGFI). BACKGROUND ALR is established in treating hepatocellular carcinoma or other malignancies to achieve curability and functional preservation. However, the conventional demarcation technique (CDT) marks only the organ surface and sometimes fails to execute a completely valid demarcation. METHODS Twenty-four consecutive ALRs for focal liver malignancy were studied using fusion IGFI. Indocyanine green was administered systemically after selective inflow clamping in 12 patients or by portal puncture and direct injection in 12 patients, and we compared demarcation findings between fusion IGFI and CDT. The strength of contrast between target and nontarget areas was quantitatively calculated as contrast index and compared between IGFI and CDT according to injection technique or state of the liver surface. RESULTS Fusion IGFI achieved valid demarcation in 23 of 24 patients (95.8%), whereas CDT achieved valid demarcation in only 10 patients (41.7%) (P < 0.0001). The contrast index of fusion IGFI was 0.81 (0.18-2.51), which was significantly higher than that of CDT at 0.12 (0.01-0.42) (P < 0.0001), and the same result was obtained regardless of the injection method or liver surface state used. ALR was conducted referring to 3-dimensional staining of target parenchyma, with no related perioperative adverse events. CONCLUSIONS Fusion IGFI is a safe imaging technique for ALR that attained valid 3-dimensional parenchymal demarcation with better feasibility and clearer demarcation than CDT.

Sinistral portal hypertension after pancreaticoduodenectomy with splenic vein ligation.

Splenic vein ligation may result in sinistral (left‐sided) portal hypertension and gastrointestinal haemorrhage. The aim of this study was to analyse the pathogenesis of sinistral portal hypertension following splenic vein ligation in pancreaticoduodenectomy.

Routine Preoperative Liver-specific Magnetic Resonance Imaging Does Not Exclude the Necessity of Contrast-enhanced Intraoperative Ultrasound in Hepatic Resection for Colorectal Liver Metastasis.

Objectives: To assess the usefulness of contrast-enhanced intraoperative ultrasound (CE-IOUS) during surgery for colorectal liver metastases (CRLM) when gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid–enhanced magnetic resonance imaging (EOB-MRI) is performed as a part of preoperative imaging work-up. Background: EOB-MRI is expected to supersede CE-IOUS, which is reportedly indispensable in surgery for CRLM. Methods: One hundred consecutive patients underwent EOB-MRI, contrast-enhanced computed tomography (CE-CT), and contrast-enhanced ultrasound within 1 month before surgery for CRLM. Conventional IOUS and subsequent CE-IOUS using perflubutane were performed after the laparotomy. All the nodules identified in any of the preoperative or intraoperative examinations were resected and were submitted for histological examination, in principle. Results: Preoperative imaging examinations identified 242 nodules; 25 additional nodules were newly identified using IOUS, 22 additional nodules were newly identified during CE-IOUS, and a histological examination further identified 4 nodules. Among the 25 nodules newly identified using IOUS, all 21 histologically proven CRLMs and 3 of the 4 benign nodules were correctly diagnosed using CE-IOUS. Among the 22 nodules newly identified using CE-IOUS, 17 nodules in 16 patients were histologically diagnosed as CRLMs. The planned surgical procedure was modified on the basis of IOUS and CE-IOUS findings in 12 and 14 patients, respectively. The sensitivity, positive-predictive value, and accuracy of CE-IOUS were 99%, 98%, and 97%, respectively. Those values of EOB-MRI (82%, 99%, 83%, respectively) were similar to CE-CT (81%, 99%, 81%, respectively). Conclusions: CE-IOUS is useful in hepatic resection for CRLM, even if EOB-MRI and CE-CT are performed.

Living donor liver transplantation using sensitized lymphocytotoxic crossmatch positive graft

We describe a successful living donor liver transplantation (LDLT) using a lymphocytotoxic crossmatch highly positive graft. A 41-year-old woman with alcoholic liver cirrhosis was referred as a potential candidate for LDLT, and her husband was willing to donate his partial liver. As the T-lymphocytotoxic crossmatch titer was over 10,000×, the patient was first infused with rituximab for preoperative desensitization, and then five rounds of plasmapheresis were performed. After the third plasmapheresis, the lymphocytotoxic crossmatch test was negative. A left liver graft including the caudate lobe was implanted, and anti-CD25 antibody (basiliximab) was administered on postoperative days 1 and 4. The postoperative course was uneventful except for an episode of mild acute cellular rejection on postoperative day 27. Although the impact of a lymphocytotoxic crossmatch-positive liver graft on acute cellular rejection and graft survival in LDLT remains controversial, perioperative desensitization may provide benefits when using a highly sensitized liver graft.

Adjuvant Oral Uracil-Tegafur with Leucovorin for Colorectal Cancer Liver Metastases: A Randomized Controlled Trial

Background The high recurrence rate after surgery for colorectal cancer liver metastasis (CLM) remains a crucial problem. The aim of this trial was to evaluate the efficacy of adjuvant therapy with uracil-tegafur and leucovorin (UFT/LV). Methods In the multicenter, open-label, phase III trial, patients undergoing curative resection of CLM were randomly assigned in a 1:1 ratio to either the UFT/LV group or surgery alone group. The UFT/LV group orally received 5 cycles of adjuvant UFT/LV (UFT 300mg/m2 and LV 75mg/day for 28 days followed by a 7-day rest per cycle). The primary endpoint was recurrence-free survival (RFS). Secondary endpoints included overall survival (OS). Results Between February 2004 and December 2010, 180 patients (90 in each group) were enrolled into the study. Of these, 3 patients (2 in the UFT/LV group and 1 in the surgery alone group) were excluded from the efficacy analysis. Median follow-up was 4.76 (range, 0.15–9.84) years. The RFS rate at 3 years was higher in the UFT/LV group (38.6%, n = 88) than in the surgery alone group (32.3%, n = 89). The median RFS in the UFT/LV and surgery alone groups were 1.45 years and 0.70 years, respectively. UFT/LV significantly prolonged the RFS compared with surgery alone with the hazard ratio of 0.56 (95% confidence interval, 0.38–0.83; P = 0.003). The hazard ratio for death of the UFT/LV group against the surgery alone group was not significant (0.80; 95% confidence interval, 0.48–1.35; P = 0.409). Conclusion Adjuvant therapy with UFT/LV effectively prolongs RFS after hepatic resection for CLM and can be recommended as an alternative choice. Trial Registration UMIN Clinical Trials Registry C000000013