Seiichiro Kai

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.

A comparative study of the long-term outcomes after laparoscopy-assisted and open left lateral hepatectomy for hepatocellular carcinoma.

Background Laparoscopic hepatectomy was initially reported in 1992. However, the reported experiences are scarce, and this operation has not been a standard procedure until now. The aims of this study were to assess our results of laparoscopy-assisted left lateral hepatectomy for hepatocellular carcinoma (HCC) and to compare them with those of open conventional procedures. Methods From 1984 to 2002, left lateral hepatectomy for HCC less than 5 cm in diameter was carried out in 21 patients. Ten patients received a laparoscopy-assisted procedure, and remaining 11 patients received an open procedure. Results There were no significant differences in the operation time, blood loss, resected liver weight, and resection margin between the 2 groups. The total time that analgesics were given, body temperature on postoperative day 1, weight loss on postoperative day 7, and postoperative hospital stay in the laparoscopic group were significantly better than in the conventional group. With regard to the long-term prognosis, there were no differences in patient survival or disease-free survival rates between the 2 groups. Conclusions Laparoscopy-assisted left lateral hepatectomy for HCC is superior to the conventional open surgery in terms of its short-term results and does not cause the long-term survival to deteriorate. Therefore, laparoscopic hepatectomy may be an alternative choice for treatment of HCC.

Prognosis of patients with intrahepatic recurrence after hepatic resection for hepatocellular carcinoma: A retrospective study

AIMS Hepatic resection is the most effective therapy for hepatocellular carcinoma (HCC); however, intrahepatic recurrence is common. Predictors of survival after intrahepatic recurrence have not been fully investigated. To clarify the prognosis and choice of treatment of intrahepatic recurrence after hepatic resection, we conducted a comparative retrospective analysis of 147 patients with HCC who underwent hepatic resection. METHODS We retrospectively examined the relations between clinicopathologic factors, including the number of recurrent intrahepatic tumors and long-term prognosis after recurrence in 147 HCC patients who underwent resection. We also examined long-term survival after recurrence based on treatment types and recurrence pattern. RESULTS Patients with multiple tumors (n=83) showed less tumor differentiation, more frequent portal invasion, a higher alpha-fetoprotein level, and larger tumors than did patients with solitary tumor (n=64). In the solitary tumor group, local ablation therapy and repeat hepatic resection were performed in 25 and 10, respectively. In the multiple tumor group, 59 were treated by transarterial chemoembolization. Multivariate analysis showed intraoperative blood transfusion and multiple tumors to be independent risk factors for poor cancer-related survival after recurrence. By subset analysis based on treatment types and recurrence pattern, survival after recurrence was significantly better in patients treated by local ablation therapy than those treated by other therapies in both solitary and multiple tumor groups. CONCLUSIONS For patients with solitary recurrence, a good prognosis is predicted. Local ablation therapy is a best candidate for treatment of solitary and multiple intrahepatic recurrences after hepatic resection.

Predictors and prognostic significance of operative complications in patients with hepatocellular carcinoma who underwent hepatic resection

AIMS The morbidity rate of hepatic resection for hepatocellular carcinoma (HCC) remains high. To clarify predictors and the prognostic significance of operative complications in patients with HCC, we conducted a comparative retrospective analysis of 291 patients with HCC who underwent hepatic resection. METHODS Operative complications included hyperbilirubinemia, ascites, hemorrhage, respiratory and cardiovascular diseases, bile leakage and abscess formation, renal failure, wound infection, and pleural effusion. Predictors of operative complications and their prognostic value for long-term survival were studied by univariate and multivariate analyses. RESULTS Mortality and morbidity rates were 7.2% and 42.6%. The main operative complications were ascites (n = 30), intraabdominal abscess (n = 25), hyperbilirubinemia (n = 19), wound infection (n = 16), pleural effusion (n = 10) and intraabdominal hemorrhage (n=9). By a multivariate logistic regression model, Child-Pugh class B and increased operative blood loss (> or = 1200ml) were independent predictors of postoperative complications. Among 243 patients without operative death, the 5-year overall survival rate was significantly lower in patients with operative complications (34.3%) than in those without these complications (48.7%). By the multivariate Cox proportional hazards model, the presence of operative complications was an independent predictor of poor overall survival as well as presence of portal invasion. CONCLUSIONS Child-Pugh class B and operative blood loss > or = 1200ml were independent predictors of complications after hepatic resection for HCC. Long-term survival is poorer in patients with postoperative complications. Decreasing operative blood loss may result in fewer postoperative complications and better long-term survival of HCC patients.

A small interfering RNA targeting proteinase‐activated receptor‐2 is effective in suppression of tumor growth in a Panc1 xenograft model

Proteinase‐activated receptor‐2 (PAR‐2), which is a G protein‐coupled receptor, is activated in inflammatory processes and cell proliferation. We previously demonstrated that an anti‐PAR‐2 antibody suppresses proliferation of human pancreatic cells in vitro. However, there have been no studies of PAR‐2 signaling pathways in vivo. The aim of this study was to determine whether blockade of PAR‐2 by RNA interference influences pancreatic tumor growth. We originally constructed small interfering RNAs (siRNAs) targeting human PAR‐2, and performed cell proliferation assays of Panc1 human pancreatic cancer cell line with these siRNAs. Intratumoral treatment with these PAR‐2 siRNAs and atelocollagen was also performed in a xenograft model with nude mice and Panc1 cells. siRNAs against human PAR‐2 inhibited proliferation of Panc1 cells, whereas control scramble siRNAs had no effect on proliferation. The PAR‐2 siRNAs dramatically suppressed tumor growth in the xenograft model. PAR‐2‐specific siRNA inhibited growth of human pancreatic cancer cells both in vitro and in vivo. Blockade of PAR‐2 signaling by siRNA may be a novel strategy to treat pancreatic cancer.

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.

Indoleamine 2,3-dioxygenase is necessary for cytolytic activity of natural killer cells.

Indoleamine 2,3‐dioxygenase (IDO) is a tryptophan catabolic enzyme that is widely distributed in various tissues. In peripheral blood mononuclear cells (PBMCs), production of IDO by macrophages or dendritic cells has been reported to inhibit T‐cell activation and proliferation. In the present study, we have determined that other phenotypes of PBMCs also express IDO. In cultures of PBMCs, IDO was found predominantly in monocyte by immunohistochemistry. Reverse transcriptase polymerase chain reaction analysis showed that IDO mRNA was expressed in T lymphocytes, B lymphocytes and natural killer (NK) cells and that expression was increased upon activation with interferon‐γ. The cytotoxicity of NK cells against K562 and HepG2 cells was reduced by IDO inhibitor. These results suggest that IDO in NK cells is essential for NK cells to generate killing activity against cancer cells.

Lymphatic invasion: an important prognostic factor for stages T1b-T3 gallbladder cancer and an indication for additional radical resection of incidental gallbladder cancer.

BackgroundLaparoscopic cholecystectomy is being performed with increasing frequency worldwide. This has led to more frequent discovery of incidental gallbladder cancer (IGBC) and in turn to the need for an independent prognostic factor for stages T1b–T3 gallbladder cancer so that is can be determined clinically which cases of IGBC are indicated for additional radical resection (ARR).MethodsA retrospective study was conducted that included 72 patients who underwent macroscopically curative surgical resection (R0, R1) at our center for stages T1b–T3 GBC. Survival analysis was performed, and the usefulness of ARR was analyzed in 15 patients with IGBC.ResultsUnivariate analysis of disease-specific survival showed stage T3, histologic grade II–IV, lymphatic invasion, vessel invasion, perineural invasion, lymph node metastasis, and a positive resection margin to be factors indicative of poor prognosis. Independent predictors of poor disease-specific survival were stage T3 (hazard ratio, 2.33 [95% CI, 1.10–4.95]), lymphatic invasion (5.97 [1.29–27.6]), and a positive resection margin (3.17 [1.51–6.63]). Among the 15 IGBC patients, 4 of 5 patients without lymphatic invasion were cured, 2 of whom underwent cholecystectomy alone; 4 of 10 patients with lymphatic invasion did not undergo ARR, and the cancer recurred in all 4 patients; the other 6 patients underwent ARR, and 4 of them were cured by reoperation.ConclusionsLymphatic invasion well reflects the malignant phenotype of stages T1b–T3 GBC. We advocate ARR for IGBC patients with lymphatic invasion.

Operative timing of laparoscopic cholecystectomy for acute cholecystitis in a Japanese institute.

These authors suggest that the best timing of laparoscopic cholecystectomy for acute cholecystitis in Japan may be within 24 hours of the onset of the disease.

Hepatitis B Virus Infection Predicts Extrahepatic Metastasis After Hepatic Resection in Patients With Large Hepatocellular Carcinoma

BackgroundAlthough extrahepatic metastasis occurs rarely after hepatic resection for hepatocellular carcinoma (HCC), the prognosis of these patients is extremely poor. Predictors of extrahepatic metastasis have not been fully investigated.MethodsTo identify predictors of extrahepatic metastasis after resection, we retrospectively investigated 77 patients with HCC tumors >50 mm in diameter who underwent hepatic resection. We investigated correlations between postoperative extrahepatic metastasis and clinicopathologic factors as well as extrahepatic metastasis-free survival rate by log rank test and predictors of extrahepatic metastasis by univariate and multivariate logistic regression models.ResultsHepatitis B surface antigen (HBs-Ag) was found in 25 (32.5%) of 77 patients, and extrahepatic metastasis occurred in 26 (33.8%). Patients with extrahepatic metastasis showed better liver function and a high occurrence of HBs-Ag positivity than those without. The 5-year extrahepatic metastasis-free survival rate was worse in patients with HBs-Ag positivity, larger tumors (≥70 mm), higher alfa-fetoprotein level (≥300 ng/mL), and lower indocyanine green retention rate at 15 minutes (ICGR15) (<15%) than in those without. By univariate logistic regression analysis, HBs-Ag positivity, larger HCC tumor (≥70 mm), lower ICGR15 (<15%), and lower preoperative lymphocyte count (<1000/mm3) were predictors of extrahepatic metastasis (P < .1). By multivariate analysis, HBs-Ag positivity was an independent predictor of postoperative extrahepatic metastasis (P = .04).ConclusionsIn patients positive for HBs-Ag, radiologic examination of extrahepatic organs should be performed as a part of the postoperative surveillance. Hepatitis B virus infection may promote establishment of extrahepatic metastasis.