Yukio Iwashita

Microsatellite distribution and indication for locoregional therapy in small hepatocellular carcinoma

Intrahepatic disease recurrence is observed frequently after locoregional therapies for patients with hepatocellular carcinoma (HCC). However, the indication for locoregional therapy is still unclear. To clarify the indication for locoregional therapy for small HCC tumors, the authors measured the distance of microsatellites from the main tumor and analyzed the relation between this distance and clinicopathologic factors.

Assessment of donor fatty livers for liver transplantation

Aim. The effect of fatty liver on graft survival, especially with reference to macrovesicular and microvesicular steatosis, is still uncertain. This preliminarily study was designed to create a noninvasive method for the quantification of the hepatic fat content in vivo and to establish provisional criteria for the assessment of fatty donor livers before liver transplantation among transplant surgeons, radiologists, and pathologists. Methods and Materials. Different degrees of rat fatty liver model were established by feeding rats a diet deficient in choline and methionine for different periods of time. Computed tomography (CT) with test tubes containing variable percentages of fat equivalent substance were used to assess the severity of fatty change of the rat liver. This was then correlated with the histological classification, level of hepatic enzymes, and graft survival. Results. Linear correlation between the fat volume fraction added to the test tubes and CT density were found. The process of producing a fatty liver via diet alteration peaked at week 3. At this time hepatic enzymes, radiological fat content, and posttransplantation survival were worse (P =0.013), compared with other time points. Radiological assessment of fatty liver correlated well with survival and serum glutamic oxaloacetic transaminase and glutamic pyruvate transaminase levels. Conclusion. Severe microvesicular steatosis does not influence recipient survival, however, macrovesicular steatosis affects graft survival. Caliber CT is a practical and simple method that allows an accurate noninvasive quantitative assessment of hepatic fatty infiltration. It has potential to be a useful parameter for the assessment of donor livers for clinical liver transplantation.

Improved long-term survival after liver resection for hepatocellular carcinoma in the modern era: retrospective study from HCV-endemic areas.

It remains unclear whether recent progress in perioperative management and treatment for recurrent hepatocellular carcinoma (HCC) has improved patient outcomes in hepatitis C virus-endemic areas. The clinicopathologic and follow-up data of 218 consecutive HCC patients who underwent curative resection between 1982 and 2003 were analyzed. Patients were assigned to one of two groups: before 1992 (early group; n = 82) and 1992 and later (late group; n = 136). Factors influencing survival rates were investigated by multivariate analysis. The effects of the period during which the hepatic resection was done on the patients’ outcome were examined with respect to tumor size. The 5-year cancer-related and disease-free survival rates were 51.4% and 20.4%, respectively. The late group showed better 5-year cancer-related survival than the early group (64.1% vs. 33.8%), but disease-free survival did not differ significantly between the groups. On multivariate analysis, the period of the hepatic resection was identified as an independent prognostic factor for cancer-related survival (relative risk 0.70, P < 0.01) but not disease-free survival. There were no differences in the cancer-related and disease-free survival rates between the two groups for patients with tumors ≤ 25 mm. In patients with HCCs > 50 mm, both cancer-related and disease-free survival rates were better in patients in the late group. During the past two decades, improvements in the treatment of recurrent HCC tumors have contributed to controlling large HCCs but not to controlling the multicentric development of HCCs. It may be important to control multicentric recurrence of HCC to improve patient survival in areas where the hepatitis C virus is endemic.

Analysis of preoperative prognostic factors for long-term survival after hepatic resection of liver metastasis of colorectal carcinoma.

Hepatic resection is the most effective therapy for liver metastasis of colorectal carcinoma. To clarify indications for this therapy, the clinicopathologic and follow-up data of 103 consecutive patients who underwent hepatic resection for metastases of colorectal carcinoma were analyzed. Factors influencing overall survival rate were investigated by multivariate analysis. Thereafter, patients who underwent resection were stratified according to the number of independent risk factors present, and their outcomes were compared with those of 14 nonresection patients with fewer than six liver tumors and without extrahepatic metastasis. The overall survival rate of the 103 resection patients was 43.1%. The clinicopathologic factors shown to affect on long-term survival after hepatic resection were the interval between colorectal and hepatic surgery (<12 months), preoperative carcinoembryonic antigen level (>-10 ng/ml), and number of hepatic metastases (four or more). The 5-year overall survival rates were 75.0% with no risk factors (n = 16), 53.6% with one risk factor (n = 46), 23.0% with two risk factors (n = 36), and0%with three risk factors (n = 5). Survival rates did not differ between resection patients with three risk factors and nonresection patients. Therefore, hepatic resection may be appropriate for patients with fewer than three risk factors.

Increased mRNA expression of chemokines in hepatocellular carcinoma with tumor-infiltrating lymphocytes

Background:  The infiltration of lymphocytes in tumor tissue has been associated with a good prognosis for patients with hepatocellular carcinoma (HCC). The purpose of the present study was to estimate the correlation between mRNA expression of chemokines and tumor‐infiltrating lymphocytes in HCC.

Chemokine receptor CCR6 as a prognostic factor after hepatic resection for hepatocellular carcinoma.

Background and Aims:  Chemokines and their receptors have recently been shown to have major roles in cancer metastasis. The aim of this study was to determine whether the interaction between chemokine receptor 6 (CCR6) and its ligand, macrophage inflammatory protein‐3 alpha (MIP‐3α), correlates with metastasis of hepatocellular carcinoma (HCC).

Comparison of enteral nutrition with combined enteral and parenteral nutrition in post-pancreaticoduodenectomy patients: a pilot study

BackgroundMany clinical studies have demonstrated that early postoperative enteral nutrition (EN) improved the postroperative course. Post-pancreaticoduodenectomy (PD), patients tend to suffer from postoperative nausea, abdominal distention, and diarrhoea, causing difficulty in the introduction of EN. In this pilot study, we investigated the appropriate nutritional mode post-pancreatic surgery.MethodsBetween October 2006 and March 2007 2 postoperative nutritional methods were implemented in 17 patients in a prospective single-centere study. Eight patients received only enteral nutrition (EN group) and 9 patients received enteral nutrition combined with parenteral nutrition (EN + PN group).ResultsThere were no differences in the patient characteristics and postoperative morbidity between the 2 groups. The rate of discontinuance of enteral feeding was significantly high in the EN group, and the duration of enteral feeding was significantly longer in the EN + PN group. The central venous line was retained for a significantly longer period in the EN + PN group, but there was no difference in the frequency of catheter-related infection between the 2 groups.ConclusionEN combined with PN is more adequate for patients after pancreatic surgery.

Expression of matrix metalloproteinase-7 is an unfavorable prognostic factor in intrahepatic cholangiocarcinoma.

BackgroundIntrahepatic cholangiocarcinoma (IHCC) is a highly malignant neoplasm, but the prognostic factors of IHCC are not yet fully understood. The matrix metalloproteinases (MMPs) are known to be related to tumor viability. The aim of this study was to evaluate the prognostic significance of clinicopathological and immunohistochemical characteristics of resected IHCC.Patients and MethodsFrom 1996 to 2006, we surgically treated 35 patients with IHCC. Clinicopathological and immunohistochemical characteristics, including expression of MMPs, vascular endothelial growth factor, and epidermal growth factor receptor in the resected specimens, were investigated, and overall survival rates were evaluated with regard to the characteristics using univariate and multivariate analyses.ResultsUnivariate analysis revealed the significant prognostic factors to be preoperative serum CEA and CA19-9, intraoperative transfusion, tumor size, surgical margin, lymph node metastasis, invasion of portal and hepatic vein, intrahepatic metastasis, UICC stage, and expression of MMP-7. Subsequent multivariate analysis indicated that MMP-7 was an independent prognostic factor (hazard ratio (HR), 4.698; 95% confidence interval (CI), 0.057–0.866; P = 0.03) along with intrahepatic metastasis (HR, 5.694; 95% CI, 0.029–0.706; P = 0.017).ConclusionMMP-7 expression is associated with a poor prognosis in patients with resected IHCC.

Tokyo Guidelines 2018: flowchart for the management of acute cholecystitis

We propose a new flowchart for the treatment of acute cholecystitis (AC) in the Tokyo Guidelines 2018 (TG18). Grade III AC was not indicated for straightforward laparoscopic cholecystectomy (Lap‐C). Following analysis of subsequent clinical investigations and drawing on Big Data in particular, TG18 proposes that some Grade III AC can be treated by Lap‐C when performed at advanced centers with specialized surgeons experienced in this procedure and for patients that satisfy certain strict criteria. For Grade I, TG18 recommends early Lap‐C if the patients meet the criteria of Charlson comorbidity index (CCI) ≤5 and American Society of Anesthesiologists physical status classification (ASA‐PS) ≤2. For Grade II AC, if patients meet the criteria of CCI ≤5 and ASA‐PS ≤2, TG18 recommends early Lap‐C performed by experienced surgeons; and if not, after medical treatment and/or gallbladder drainage, Lap‐C would be indicated. TG18 proposes that Lap‐C is indicated in Grade III patients with strict criteria. These are that the patients have favorable organ system failure, and negative predictive factors, who meet the criteria of CCI ≤3 and ASA‐PS ≤2 and who are being treated at an advanced center (where experienced surgeons practice). If the patient is not considered suitable for early surgery, TG18 recommends early/urgent biliary drainage followed by delayed Lap‐C once the patients overall condition has improved. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.

Mammalian target of rapamycin signaling activation patterns in pancreatic neuroendocrine tumors

Phosphatidylinositol 3‐kinase/Akt/mammalian target of rapamycin (mTOR) pathway dysregulation has been implicated in the development of various human cancers. However, expression of mTOR cascade components in pancreatic neuroendocrine tumors (PNETs) has not been fully explored. The aim of this study was to assess the expression of mTOR pathway in PNETs using immunohistochemistry.