Suguru Yamashita

Portal uptake function in veno-occlusive regions evaluated by real-time fluorescent imaging using indocyanine green

BACKGROUND & AIMS Although recent advances in preoperative imaging have enabled accurate estimation of the regional liver volume with venous occlusion, the extent of functional decrease in such regions remains unclear. In this study, the portal uptake function in postoperative veno-occlusive regions and non-veno-occlusive regions was evaluated by intraoperative fluorescent imaging after intravenous injection of indocyanine green (ICG). METHODS In 22 liver resection patients and 23 recipients and 18 donors of liver transplantation, fluorescent intensity on the remnant liver or the liver graft was evaluated in real time following intravenous injection of ICG (0.0025 mg per 1 ml of remnant liver volume). RESULTS Plateau ICG concentrations were significantly lower in the veno-occlusive regions (C(VO)) than in the non-veno-occlusive regions (C(Non)) in liver resection patients (median [range], 0.75 [0.29-2.0]μg/ml vs. 3.0 [0.46-6.4]μg/ml, p<0.001), donors (0.69 [0.29-1.9]μg/ml vs. 2.4 [0.46-6.4]μg/ml, p<0.001), and recipients (0.75 [0.34-1.8]μg/ml vs. 1.8 [0.54-6.4]μg/ml, p<0.001). Distributions of the C(VO)/C(Non) and the ratio of the hepatic uptake rate constant in the veno-occlusive regions to that in non-veno-occlusive regions were both around 40% (mean ± standard deviation, 0.36 ± 0.17 and 0.42 ± 0.16, respectively). When the functional remnant liver volume was calculated as a sum of non-veno-occlusive regions and veno-occlusive regions multiplied by C(VO)/C(Non), its ratio to the total liver volume was correlated with the improved postoperative/preoperative ratio of prothrombin time. CONCLUSIONS Portal uptake function in veno-occlusive regions is approximately 40% of that in non-veno-occlusive regions. Intraoperative ICG-fluorescent imaging enables real-time evaluation of the extent of the functional decrease in veno-occlusive regions, enhancing accurate estimation of the hepatic functional reserve for determining the surgical indications and procedures.

Visualization of the leakage of pancreatic juice using a chymotrypsin-activated fluorescent probe

Pancreatic fistula (PF) remains the most serious complication after digestive surgery. It is difficult to prevent because of the inability to visualize the leakage of pancreatic juice during surgery or to evaluate the protease activity of leaked fluid, which is responsible for PF formation.

Pancreas-sparing duodenectomy for gastrointestinal stromal tumor

BACKGROUND Pancreas-sparing duodenectomy (PSD) is a promising alternative procedure to pancreaticoduodenectomy for the treatment of duodenal tumors with low-grade malignant behavior. METHODS Between March 2003 and September 2012, PSD was performed in 7 patients with a gastrointestinal stromal tumor (GIST) in the second (n = 5) or third (n = 2) portions of the duodenum. The short- and long-term outcomes of treatment were analyzed in all patients. RESULTS The median blood loss was 160 mL, and the median operative time was 315 minutes. No pancreatic leakage or perioperative mortality occurred. Surgical margins were negative in all cases. All patients were alive at the median follow-up time of 42 months after PSD. The recurrence-free 5-year survival rate was 53% in all patients. Hepatic metastases developed in 2 of the 5 patients with high- or intermediate-grade risks at the time of diagnosis. Hepatic resection was performed, and imatinib mesylate was administered in the 2 cases. CONCLUSIONS Good short- and long-term outcomes and surgical curability were observed in patients treated with PSD for duodenal GIST.

RAS Mutation Clinical Risk Score to Predict Survival After Resection of Colorectal Liver Metastases.

Objective: To determine the impact of RAS mutation status on the traditional clinical score (t-CS) to predict survival after resection of colorectal liver metastases (CLM). Background: The t-CS relies on the following factors: primary tumor nodal status, disease-free interval, number and size of CLM, and carcinoembryonic antigen level. We hypothesized that the addition of RAS mutation status could create a modified clinical score (m-CS) that would outperform the t-CS. Methods: Patients who underwent resection of CLM from 2005 through 2013 and had RAS mutation status and t-CS factors available were included. Multivariate analysis was used to identify prognostic factors to include in the m-CS. Log-rank survival analyses were used to compare the t-CS and the m-CS. The m-CS was validated in an international multicenter cohort of 608 patients. Results: A total of 564 patients were eligible for analysis. RAS mutation was detected in 205 (36.3%) of patients. On multivariate analysis, RAS mutation was associated with poor overall survival, as were positive primary tumor lymph node status and diameter of the largest liver metastasis >50 mm. Each factor was assigned 1 point to produce a m-CS. The m-CS accurately stratified patients by overall and recurrence-free survival in both the initial patient series and validation cohort, whereas the t-CS did not. Conclusions: Modifying the t-CS by replacing disease-free interval, number of metastases, and CEA level with RAS mutation status produced an m-CS that outperformed the t-CS. The m-CS is therefore a simple validated tool that predicts survival after resection of CLM.

Recent Advances in Chemotherapy and Surgery for Colorectal Liver Metastases.

Background: The liver is the most common site of metastases for colorectal cancer, and combined resection with systemic chemotherapy is the most effective strategy for survival. The aim of this article is to provide a comprehensive summary on four hot topics related to chemotherapy and surgery for colorectal liver metastases (CLM), namely: (1) chemotherapy-related liver injuries: prediction and impact, (2) surgery for initially unresectable CLM, (3) the emerging role of RAS mutations, and (4) the role of hepatic arterial infusion of chemotherapy (HAIC). Summary and Key Messages: (1) The use of chemotherapy before liver resection for CLM leads to drug-specific hepatic toxicity, which negatively impacts posthepatectomy outcomes. (2) Curative liver resection of initially unresectable CLM following conversion chemotherapy should be attempted whenever possible, provided that a safe future liver remnant volume is achieved. (3) For CLM, RAS mutation status is needed to guide the use of targeted chemotherapy with anti-epithelial growth factor receptor (EGFR) agents, and is a major prognostic factor that may contribute to optimize surgical strategy. (4) HAIC agents increase the rate of objective response and the rate of complete pathological response.

Intraoperative imaging of hepatic cancers using γ-glutamyltranspeptidase-specific fluorophore enabling real-time identification and estimation of recurrence

Abstractγ-Glutamyltranspeptidase (GGT) is upregulated in a variety of human cancers including primary and secondary hepatic tumors. This motivated us to use γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), a novel fluorophore emitting light at around 520 nm following enzymatic reaction with GGT, as a tool for the intraoperative identification of hepatic tumors. gGlu-HMRG was topically applied to 103 freshly resected hepatic specimens. Fluorescence imaging using gGlu-HMRG identified hepatic tumors with the sensitivity/specificity of 48%/96% for hepatocellular carcinoma, 100%/100% for intrahepatic cholangiocarcinoma, and 87%/100% for colorectal liver metastasis. High gGlu-HMRG fluorescence intensity was positively associated with the incidence of microscopic vascular invasion in HCC and the risk of early postoperative recurrence in CRLM. These results suggest that gGlu-HMRG imaging could not only be a useful intraoperative navigation tool but also provide information related to postoperative disease recurrence.

Deleterious Effect of Ras and Evolutionary High-risk Tp53 Double Mutation in Colorectal Liver Metastases

Objective: To assess the impact of somatic gene mutations on survival among patients undergoing resection of colorectal liver metastases (CLM). Background: Patients undergoing CLM resection have heterogeneous outcomes, and accurate risk stratification is necessary to optimize patient selection for surgery. Methods: Next-generation sequencing of 50 cancer-related genes was performed from primary tumors and/or liver metastases in 401 patients undergoing CLM resection. Missense TP53 mutations were classified by the evolutionary action score (EAp53)—a novel approach that dichotomizes mutations as low or high risk. Results: The most frequent somatic gene mutations were TP53 (65.6%), followed by KRAS (48.1%) and APC (47.4%). Double mutation in RAS/TP53, identified in 31.4% of patients, was correlated with primary tumor location in the right colon (P = 0.006). On multivariable analysis, RAS/TP53 double mutation was an independent predictor of shorter overall survival (hazard ratio 2.62, 95% confidence interval 1.41–4.87, P = 0.002). In patients with co-mutated RAS, EAp53 high-risk mutations were associated with shorter 5-year overall survival of 12.2%, compared with 55.7% for TP53 wild type (P < 0.001). The negative prognostic effects of RAS and TP53 mutations were limited to tumors harboring mutations in both genes. Conclusions: Concomitant RAS and TP53 mutations are associated with decreased survival after CLM resection. A high EAp53 predicts a subset of patients with worse prognosis. These preliminary analyses suggest that surgical resection of liver metastases should be carefully considered in this subset of patients.

Intraoperative visualization of pancreatic juice leaking from the pancreatic stump in a swine model.

© 2015 by the AGA Institute 0016-5085/

Iliopsoas Muscle Hematoma Secondary to Alcoholic Liver Cirrhosis

36.00 http://dx.doi.org/10.1053/j.gastro.2015.07.068 Dresections worldwide, effective techniques for the prevention of postoperative pancreatic fistula (PF) have not been developed to date. Even a century after the initial attempts at pancreatic resection, PF still occurs with an incidence of 60% after pancreatic resection and remains the most serious complication of digestive surgery associated with mortality. Preventing pancreatic leak is difficult because surgeons have no means of visualizing clear pancreatic juice during surgery.

Resection of the second portion of the duodenum sacrificing the minor papilla but preserving the pancreas for a recurrent duodenal adenocarcinoma: report of a case.

Iliopsoas muscle hematoma in a patient with alcoholic liver cirrhosis is rarely seen, however it has a high mortality. Thus we should cautiously make a diagnosis and treatment. This is the case of a 60-year-old male. He had a 15-year history of alcoholic liver disease and emphysema. He presented with low back pain after a fall that had happened 2 months before. Due to persistent back pain, he went to see a local physician who, after detailed examination, suspected rupture of bilateral common iliac artery aneurysms and transferred the patient to our hospital. The same presumptive diagnosis was made, and on this basis, an aortic bifemoral Y-graft was implanted. He developed aspiration pneumonia and hepatic and renal dysfunction postoperatively, which led to multiple organ failure and subsequent in-hospital death on postoperative day 62. This was believed to be a case of iliopsoas muscle hematoma developed in a patient with liver cirrhosis, and considering it was a case with poor surgical risk, a conservative treatment option such as transcatheter arterial embolization should also have been considered. Although iliopsoas muscle hematoma with alcoholic liver cirrhosis is rare, an appropriate treatment plan should be determined on a case-by-case basis despite its poor prognosis.