Morihiko Ishizaki

Predictors of microvascular invasion before hepatectomy for hepatocellular carcinoma.

Microvascular invasion (MVI) is difficult to detect before resection of hepatocellular carcinoma (HCC).

Intraoperative indocyanine green fluorescent imaging for prevention of bile leakage after hepatic resection

BACKGROUND Bile leakage is a common complication of hepatectomy, and is associated with an increase in sepsis and liver failure. There are no standard preventive methods against bile leakage after hepatic surgery. The aim of the present randomized clinical trial was to evaluate the application of indocyanine green (ICG) fluorescent cholangiography for preventing postoperative bile leakage. METHODS 102 patients who underwent hepatic resection without biliary reconstruction were divided into 2 groups. The control group (n = 50) underwent a leak test with ICG dye alone, and the experimental group underwent a leak test with ICG dye, followed by ICG fluorescent cholangiography using the Photodynamic Eye (PDE group, n = 52). RESULTS Among 42 patients with fluorescence in the PDE group, 25 patients had insufficient closure of bile ducts on the cut surface of the liver, which were closed by suture or ligation. There were 5 patients who developed postoperative bile leakage in the control group versus no bile leakage in the PDE group (10% vs 0%, P = .019). CONCLUSION ICG fluorescent cholangiography could detect insufficiently closed bile ducts that could not be identified by a standard bile leak test. ICG fluorescent cholangiography may have useful potential for prevention of bile leakage after hepatic resection.

Hepatic resection for hepatocellular carcinoma in the elderly

Aging of the population has significantly increased the number of elderly patients undergoing surgery for hepatocellular carcinoma (HCC). We aimed to compare the results of hepatectomy for HCC in patients ≥70 years old with those for younger patients.

Risk factors and outcome of early recurrence after resection of small hepatocellular carcinomas

BACKGROUND This study aimed to clarify risk factors for early recurrence and examine the subsequent outcome in patients undergoing potentially R0 resection of small hepatocellular carcinomas (HCCs) (<or=2 cm in greatest dimension). METHODS Eighty-nine patients were divided into 2 groups as follows: 26 patients suffering from recurrence within 2 years of surgery (early recurrence group) and 63 patients who were disease-free for at least 2 years (disease-free 2Y group). RESULTS Only 7 of 63 patients (11%) from the group that was disease-free for at least 2 years died during the 5-year period after surgery, whereas 13 of 26 patients (50%) from the early recurrence group died. Multivariate analysis showed that the preoperative maximum removal rate of technetium-99m-diethylenetriamine pentaacetic acid-galactosyl human serum albumin and microscopic vascular invasion were independent predictors of the early recurrence of small HCC. CONCLUSIONS Early recurrence of small HCC is the leading cause of death within 5 years after R0 resection. The preoperative hepatic functional reserve influences early recurrence, even in patients with small tumors.

Timing of Resection for Synchronous Liver Metastases from Colorectal Cancer

BackgroundThis study aimed to compare the surgical outcome and long-term survival between simultaneous and delayed resection of liver metastases from colorectal cancer (LM), and to identify the factors influencing hepatic disease-free survival in patients with synchronous LM.MethodsSeventy-four patients with LM were divided into two groups, i.e., 32 patients who underwent hepatectomy at the time of colorectal surgery (simultaneous group) and 42 patients who underwent delayed liver resection (delayed group).ResultsThe hepatic disease-free survival rates of patients from the delayed group with either ≥3 or <3 liver metastases were significantly better than that of the simultaneous group. Multivariate analysis showed that simultaneous resection was one of three independent prognostic indicators with an influence on hepatic disease-free survival. In 13 of the 42 (31%) patients from the delayed group, new metastatic lesions were found in the same and/or different segments after re-evaluation during the interval between operations. These patients had a higher incidence of poorly differentiated or mucinous adenocarcinoma, shorter interval between procedures, and larger tumors than patients without tumor progression.ConclusionsTumor progression could be recognized and occult metastases were detected during the interval between operations. Delayed resection of synchronous LM may be useful to reduce the risk of rapid recurrence in the remnant liver. Patients with poorly differentiated or mucinous adenocarcinoma and those with larger tumors who undergo delayed liver resection should receive neoadjuvant chemotherapy during the interval between operations.

Clinicopathologic characteristics of patients with non-B non-C hepatitis virus hepatocellular carcinoma after hepatectomy.

BACKGROUND A substantial population of hepatocellular carcinoma (HCC) patients is negative for markers of hepatitis B virus and hepatitis C virus (HCV) infection (non-B non-C hepatitis virus [NBC]). METHODS Clinicopathologic data and outcomes were compared retrospectively for HCC patients with hepatitis B virus, HCV, and NBC who had undergone hepatectomy. RESULTS The TNM stage was significantly higher, and the prevalence of cirrhosis was significantly lower, in the NBC group compared with the HCV group. Among patients with a maximum tumor diameter of 5 cm or less, the survival rates were significantly higher in the NBC group than in the HCV group. Multivariate analysis revealed that preoperative serum des-gamma-carboxy prothrombin (DCP) level was a prognostic factor for survival in NBC-HCC patients. The DCP/tumor size ratio was significantly higher in NBC-HCC patients with normal liver histology than in patients with hepatitis or cirrhosis. CONCLUSIONS NBC-HCC patients had more advanced tumors compared with HCV-HCC patients, but significantly higher survival rates. Measurement of DCP potentially is significant for early diagnosis of NBC HCC, which may increase the chance of curative therapy without recurrence.

Protective effect of FR183998, a Na+/H+ exchanger inhibitor, and its inhibition of iNOS induction in hepatic ischemia-reperfusion injury in rats.

Recent evidence indicates that inhibition of the Na+/H+ exchanger improves heart and brain injuries induced by I/R. Studies were performed to investigate whether FR183998, a Na+/H+ exchanger inhibitor, has protective effects on hepatic I/R injury in rats. Male Sprague-Dawley rats were subjected to 70% hepatic ischemia by occluding the hepatic artery, portal vein, and bile duct associated with the left and median liver lobes with a microvascular clip for 2 h. FR183998 (1 mg/kg) was administered i.v. 10 min before the hepatic ischemia. Hepatic I/R increased the serum levels of aspartate transaminase, alanine transaminase, and lactate dehydrogenase, which peaked at 9 h after reperfusion. FR183998 reduced these injury markers and recovered liver functions. Histopathologic analysis revealed that FR183998 prevented the incidences of hepatic necrosis, apoptosis, and neutrophil infiltration at 6 and 9 h (P < 0.05). FR183998 reduced the increases in proinflammatory cytokines such as TNF-&agr; (1 - 6 h), IL-6 (1 - 12 h), interferon-&ggr; (6 - 12 h), IL-1&bgr; (1 - 3 h), and cytokine-induced neutrophil chemoattractant 1 (1-3 h), but enhanced the anti-inflammatory cytokine IL-10 (1 h). FR183998 inhibited the hepatic I/R-induced activation of the transcription factor nuclear factor-&kgr;B at 1 to 6 h and reduced the induction of iNOS at 6 to 12 h, followed by inhibition of nitric oxide production. Furthermore, FR183998 decreased the expression of the iNOS gene antisense transcript, which is involved in the stability of iNOS messenger RNA, at 9 to12 h in the liver of hepatic I/R rats. These results demonstrate that FR183998 reduces the induction of proinflammatory cytokines and iNOS at least in part through inhibition of nuclear factor-&kgr;B activation and iNOS antisense transcript expression, thereby preventing hepatic I/R injury.ABBREVIATIONS - NHE-Na+/H+ exchanger; I/R-ischemia/reperfusion; NO-nitric oxide; iNOS-inducible nitric oxide synthase; TNF-&agr;-tumor necrosis factor-&agr;; CINC-1-cytokine-induced neutrophil chemoattractant 1; IFN-&ggr;-interferon-&ggr;; IL-interleukin; NF-&kgr;B-nuclear factor-&kgr;B

Usefulness of Tc-99m-GSA scintigraphy for liver surgery

Postoperative mortality remains high after hepatectomy compared with other types of surgery in patients who have cirrhosis or chronic hepatitis. Although there are several useful perioperative indicators of liver dysfunction, no standard markers are available to predict postoperative liver failure in patients with hepatocellular carcinoma (HCC) undergoing hepatectomy. The best preoperative method for evaluating the hepatic functional reserve of patients with HCC remains unclear, but technetium-99m diethylenetriamine pentaacetic acid galactosyl human serum albumin (99mTc-GSA) scintigraphy is a candidate. 99mTc-GSA is a liver scintigraphy agent that binds to the asialoglycoprotein receptor, and can be used to assess the functional hepatocyte mass and thus determine the hepatic functional reserve in various physiological and pathological states. The maximum removal rate of 99m Tc-GSA (GSA-Rmax) calculated by using a radiopharmacokinetic model is correlated with the severity of liver disease. There is also a significant difference of GSA-Rmax between patients with chronic hepatitis and persons with normal liver function. Regeneration of the remnant liver and recurrence of hepatitis C virus infection in the donor organ after living donor liver transplantation have also been investigated by 99mTc-GSA scintigraphy. This review discusses the usefulness of 99mTc-GSA scintigraphy for liver surgery.

Stimulation of liver regeneration after hepatectomy in mice by injection of bone marrow mesenchymal stem cells via the portal vein.

AIM To investigate whether mouse bone marrow mesenchymal stem cells (BMC) stimulate liver regeneration after partial hepatectomy. METHODS Isolated BMCs were purified by density gradient centrifugation. We performed a 70% hepatectomy in male BALB/c mice followed by injection of BMCs into the portal vein (PV-BMC group), or the tail vein (IV-BMC group), or of saline into the portal vein (control group). RESULTS The wet weight of the liver remnant increased significantly in the PV-BMC group at 3 and 5 days after hepatectomy compared with the IV-BMC and control groups. The Ki-67 labeling index revealed that the increase to result from stimulation of DNA synthesis. The constitutive interleukin-6 and hepatocyte growth factor mRNAs in the remnant liver tended to increase in the PV-BMC group at 3 days after hepatectomy. CONCLUSIONS These results demonstrated that BMC injection into the portal vein enhanced liver growth after partial hepatectomy in mice.

Antibiotic Prophylaxis in Laparoscopic Cholecystectomy: A Randomized Controlled Trial

Background Recent meta-analyses concluded that antibiotic prophylaxis is not warranted in low-risk laparoscopic cholecystectomy. However, most trials in the meta-analyses had a relatively small sample size and were statistically underpowered. In addition, many of the trials mentioned potential cost savings owing to the elimination of prophylactic antibiotics. However, no trial has statistically estimated the cost effectiveness. To evaluate the results of meta-analyses, we conducted a randomized controlled trial on the role of prophylactic antibiotics in low-risk laparoscopic cholecystectomy with an adequate sample size. Methods From March 2007 to May 2013, at the Department of Surgery, Kansai Medical University, patients who were scheduled for elective laparoscopic cholecystectomy were randomly assigned to one of two arms: those who were and were not administered prophylactic antibiotics. The primary endpoint was the occurrence of postoperative infections and secondary endpoints were postoperative hospital stay and medical costs. Findings During the study period, 518 patients were assigned to the Antibiotics group and 519 to the No antibiotics group. Occurrences of surgical site infections, distant infections and overall infections were significantly lower in the Antibiotics group than in the No antibiotics group (0.8 vs. 3.7%, p = 0.001, OR: 0.205 (95%CI: 0.069 to 0.606); 0.4 vs. 3.1%, p = 0.0004, OR: 0.122 (95%CI: 0.028 to 0.533); 1.2 vs. 6.7%; p<0.0001, OR: 0.162 (95%CI: 0.068 to 0.389), respectively). The postoperative hospital stay was significantly shorter in the Antibiotics group (mean, SD: 3.69±1.56 vs. 4.07±3.00; p = 0.01) and the postoperative medical costs were significantly lower in the Antibiotics group (mean, SD: