Hisao Wakabayashi

Hepatic Resection for Metastatic Tumors From Gastric Cancer

ObjectiveTo assess the surgical results and clinicopathologic features of hepatic metastases from gastric adenocarcinoma to identify patients with a better probability of survival. Summary Background DataMany studies have reported the benefit of hepatic resection for metastatic tumors from colorectal cancer. However, indications for a surgical approach for gastric adenocarcinoma involving the liver have not been clearly defined. MethodsNinety (11%) of 807 patients with primary gastric cancer were diagnosed with synchronous (n = 78) or metachronous (n = 12) hepatic metastases. Of these, 19 underwent 20 resections intended to cure the metastatic lesion in the liver. The clinicopathologic features of the hepatic metastases in, and the surgical results for, the 19 patients were analyzed. ResultsThe actuarial 1-year, 3-year, and 5-year survival rates after hepatic resection were, respectively, 77%, 34%, and 34%, and three patients survived for more than 5 years after surgery. Solitary and metachronous metastases were significant determinants for a favorable prognosis after hepatic resection. Pathologically, a fibrous pseudocapsule between the tumor and surrounding hepatic parenchyma was found in 13 of the 19 patients (68%). The presence of a peritumoral fibrous pseudocapsule and a well-differentiated histologic type of metastatic nodule were significant prognostic factors. Factors associated with the primary lesion were not significant prognostic determinants in patients who underwent curative resection of the primary cancer. ConclusionsSolitary and metachronous metastases from gastric cancer should be treated by a surgical approach and confer a better prognosis. A new prognostic factor, the presence of a pseudocapsule, may be helpful in defining indications for postoperative adjuvant treatment.

COLOR: A Randomized Clinical Trial Comparing Laparoscopic and Open Resection for Colon Cancer

Background: Laparoscopic surgery has proven to be safe and effective. However, the value of laparoscopic resection for malignancy in terms of cancer outcome can only be assessed by large prospective randomized clinical trials with sufficient follow-up. Methods: COLOR (COlon carcinoma Laparoscopic or Open Resection) is a European multicenter randomized trial which has started in September 1997. In 24 hospitals in Sweden, The Netherlands, Germany, France, Italy and Spain, 1,200 patients will be included. The primary end point of the study is cancer-free survival after 3 years. Results: Within <2 years, more than 540 patients have been randomized for right hemicolectomy (45%), left hemicolectomy (10%) and sigmoidectomy (45%). 33 patients (6%) were excluded after randomization. The accrual rate is approximately 25 patients/month. Current survival rates for the whole study group are: stage I: 95%, stage II: 98%, stage III: 93%, stage IV: 64%. For all patients with stage I disease, the mortality was not cancer related. Conclusions: Although laparoscopic surgery appears of value in colorectal malignancy, results of randomized trials have to be awaited to determine the definitive place of laparoscopy in colorectal cancer. Considering the current accrual rate, the COLOR study will be completed in 2002.

Effect of preoperative portal vein embolization on major hepatectomy for advanced-stage hepatocellular carcinomas in injured livers: A preliminary report

With the aim of minimizing postoperative liver dysfunction and promoting increased resectability, we employed portal vein embolization (PVE). In this study, the effect of PVE on major hepatic resection for advanced-stage hepatocellular carcinoma (HCC) in injured livers was evaluated. PVE was performed prior to hepatectomy in 13 patients with stage III and IV HCCs. Following PVE, right trisegmentectomy was performed in 3 patients, extended right lobectomy in 3 and right lobectomy in 7. To evaluate the effect of PVE, the changes in liver functional capacity and estimated remnant liver volume (ERLV), determined by computed tomography, were examined before and after PVE. The operative morbility, mortality, and survival rates after hepatectomy were also assessed. By 2 weeks after PVE, ERLV had increased in all patients, by an average of 28%, and the mean resection rates had decreased from 70.0% to 62.2%. Postoperatively, the 30-day mortality rate was 15.3%, and the 1- and 2-year survival rates were 69% and 46%, respectively. The results of this study indicate that resectability can be increased, and major hepatectomy can be made safer by employing PVE preoperatively, in view of the fact that major hepatectomy was not considered feasible without PVE in these patients.

Is preoperative portal vein embolization effective in improving prognosis after major hepatic resection in patients with advanced-stage hepatocellular carcinoma?

The impact of the use of preoperative portal vein embolization (PVE) on long‐term survival after surgery was evaluated by retrospective analysis of prognostic factors in patients with advanced‐stage hepatocellular carcinoma (HCC) who had undergone hepatic resection with or without PVE.

Evaluation of delayed additional FDG PET imaging in patients with pancreatic tumour.

AimTo evaluate whether delayed fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging is more helpful in differentiating between malignant and benign lesions and whether delayed FDG PET imaging can identify more lesions in patients in whom pancreatic cancer is suspected. MethodsThe study evaluated 86 patients who were suspected of having pancreatic tumours. FDG PET imaging (whole body) was performed at 1 h (early) post-injection and repeated 2 h (delayed) after injection only in the abdominal region. Qualitative and semi-quantitative evaluation was performed. The semi-quantitative analysis was performed using the standardized uptake value (SUV), obtained from early and delayed images (SUVearly and SUVdelayed, respectively). Retention index (RI) was calculated according to the equation: (SUVdelayed–SUVearly)×100/SUVearly. ResultsThe final diagnosis was pancreatic cancer in 55 and benign disease in 31 patients. On visual and semi-quantitative analysis, the diagnostic accuracy of RI was the highest (88%). The differences between the SUVearly, SUVdelayed and RI value in both pancreatic cancer and benign disease were significant (P<0.01). The mean value of SUVdelayed was significantly higher than that of SUVearly (P<0.01) in pancreatic cancer. Furthermore, new foci of metastasis were seen in the liver in two patients and in the lymph node in one patient only on delayed images. ConclusionsThe RI values obtained using early and delayed FDG PET may help in evaluating pancreatic cancer. Furthermore, addition of delayed FDG PET imaging is helpful to identify more lesions in patients with pancreatic cancer.

99mTc-GSA liver dynamic SPECT for the preoperative assessment of hepatectomy.

Objective: The purpose of the present study was to devise a predictive index to predict residual liver function before hepatic resection, using technetium-99m diethylenetriamine-penta-acetic acid-galactosyl human serum albumin (99mTc-GSA) liver dynamic single photon emission computed tomography (SPECT).Methods: Fifty-seven patients with liver disease underwent liver dynamic SPECT with99mTc-GSA. Dynamic SPECT was performed to obtain the k-value according to the accumulation curve after injection of99mTc-GSA. The k-value is a mathematical reflection of the rate of disappearance of the circulating radiotracer as it is accumulated into the hepatocytes. We devised an original predictive residual index (PRI) by combining k-value with liver volume (V) and functional liver volume (FV). Correlation between these parameters and results of liver function tests and the grade of liver disease severity was analyzed. We investigated retrospectively the correlation between PRI and post-operative patient prognosis.Results: The k-value slightly correlated with indocyanine green clearance test at 15 mins, bilirubin level and hepaplastin test. FV and V did not correlate with liver function tests. Post-operative complications were observed in 5 patients. The PRI of these patients was below 0.37. When PRI was above 0.38, no patient had hepatic failure.Conclusions: When PRI is above 0.38, there is a low probability of hepatic failure after hepatectomy. The PRI is useful in preoperative prediction of post-hepatectomy residual liver function in patients with liver disease.

Ischemic preconditioning of the murine liver protects through the akt kinase pathway

Hepatic ischemia‐reperfusion (I/R) injury occurs in the settings of transplantation, trauma, and elective liver resection. Ischemic preconditioning has been used as a strategy to reduce inflammation and organ damage from I/R of the liver. However, the mechanisms involved in this process are poorly understood. We examined the role of the phosphatidylinositol 3 (PI3) kinase/Akt‐signaling pathway during hepatic ischemic preconditioning (IPC). Prior to a prolonged warm ischemic insult, BALB/c mice were subjected to a 20‐minute IPC period consisting of 10 minutes of ischemia and 10 minutes of reperfusion. Mice undergoing IPC demonstrated a significantly greater level and earlier activation of Akt in the liver compared with control animals. IPC also resulted in markedly less hepatocellular injury and improved survival compared with control animals. Akt activation associated with hepatic IPC suppressed the activity of several modulators of apoptosis, including Bad, glycogen synthase kinase β, and caspase‐3. In addition, IPC also inhibited the activities of c‐Jun N‐terminal kinase and nuclear factor κB after I/R. Pretreatment of mice with PI3 kinase inhibitors completely abolished Akt phosphorylation and the protective effects seen with IPC. In conclusion, these results indicate that the PI3 kinase/Akt pathway plays an essential role in the protective effects of IPC in hepatic I/R injury. Modulation of this pathway may be a potential strategy in clinical settings of ischemic liver injury to decrease organ damage. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270‐9139/suppmat/index.html). (HEPATOLOGY 2006;44:573–580.)

Measurement of Serum Hyaluronate as a Predictor of Human Liver Failure after Major Hepatectomy

Serum hyaluronate can be used as an index of hepatic sinusoidal endothelial cell function. This study was designed to evaluate its application as a predictor of liver failure after major hepatectomy. Thirty-six patients who underwent right liver lobectomy after percutaneous transhepatic right branch portal vein embolization were divided into two groups based on their postoperative clinical course (groups 1 and 2, with and without postoperative liver failure, n= 6 and n= 30, respectively). We serially measured serum hyaluronate levels using a sandwich binding protein assay system before and after hepatectomy and determined relations with progression of the underlying chronic liver disorder, portal venous pressure, and liver growth of the left lobe after portal embolization. Serum hyaluronate levels were significantly elevated, in line with the degree of severity of the underlying chronic liver disorder, and correlated well with the portal venous pressure and the hypertrophic ratio of the left lobe subsequent to portal embolization. Serum hyaluronate levels in group 1 were significantly higher than those in group 2 before surgery and increased steeply during the early period after hepatectomy. These results suggest that the serum hyaluronate reflects the hepatic functional reserve, and serial measurement of this parameter after hepatectomy can serve as a simple indicator for early detection of posthepatectomy liver failure.

PREDICTION OF THE EARLY PROGNOSIS OF THE HEPATECTOMIZED PATIENT WITH HEPATOCELLULAR CARCINOMA WITH A NEURAL NETWORK

The early prognosis of the hepatectomized patients with hepatocellular carcinoma was determined preoperatively with a perceptron-type neural network. The neural network was trained with the preoperative data of 54 example cases with the early prognosis, successful or died of hepatic dysfunction, as teaching signals. After learning these examples, the neural network came to give a precise prediction to the example data except for one case. With the learned neural network, the outcomes of the hepatectomy of 11 patients (10 successful; 1 died) were predicted prospectively with 100% precision. The usefulness of the neural network for the prediction was determined.

A simple and safe pancreas transection using a stapling device for a distal pancreatectomy

Pancreatic fistula is the most common major complication to occur after distal pancreatectomy, ranging in frequency from 5% to 40%. The appropriate technique for treating the pancreatic stump still remains controversial. Thirty-six patients underwent distal pancreatectomy in Kagawa University Hospital between January 2000 and February 2007. Their hospital records were reviewed to evaluate the usefulness of a stapling closure using several types of staplers in comparison to a suture closure. They were subdivided according to the method used to close the pancreas stump: the suture group comprised 11 patients, the staple group comprised 24 patients, including 7 patients for whom was used the new endopath stapler Echelon 60 (Ethicon Endo-surgery; Johnson & Johnson, Cincinnati, OH, USA). Overall pancreatic fistula rate was 17% (6/36) in this series. In the staple group, 3 of the 24 patients (12%) developed a pancreatic fistula, whereas in the suture group, 3 of 11 patients (27%) developed a pancreatic fistula. Of the 7 patients for whom the Echelon 60 was used, none developed a pancreatic fistula. The length of postoperative hospital stay was also significantly shorter for the patients with the Echelon 60 than in the patients either with sutures or another stapling device. These findings support the advantages of using a stapler closure in distal pancreatectomy. This method, using a new stapler device, is considered to be a simple and safe alternative to the standard suture closure technique.