Intraoperative support with three-dimensional holographic cholangiography in hepatobiliary surgery.

PURPOSE: This study was performed to investigate the potential of intraoperative three-dimensional (3D) holographic cholangiography, which provides a computer graphics model of the biliary tract, with mixed reality techniques. METHODS: Two patients with intraductal papillary neoplasm of the bile duct were enrolled in the study. Intraoperative 3D cholangiography was performed in a hybrid operating room. Three-dimensional polygon data using the acquired cholangiography data were installed into a head mount display (HoloLens; Microsoft Corporation, Redmond, WA, USA). RESULTS: Upon completion of intraoperative 3D cholangiography, a hologram was immediately and successfully made in the operating room using the acquired cholangiography data, and several surgeons wearing the HoloLens succeeded in sharing the same hologram. Compared with usual two-dimensional cholangiography, this 3D holographic cholangiography technique contributed to more accurate reappearance of the bile ducts, especially the B1 origination site, and moving the hologram from the respective operators' angles by means of easy gesture-handling without any monitors. CONCLUSION: Intraoperative 3D holographic cholangiography might be a new next-generation operation-support tool in terms of immediacy, accurate anatomical reappearance, and ease of handling.

Significance of Frailty in Prognosis After Hepatectomy for Elderly Patients with Hepatocellular Carcinoma.

BACKGROUND: The concept of frailty becomes important for patients who undergo surgery in this recent aging society. The aim of this study is to investigate the frailty as a prognostic factor in elderly patients with hepatocellular carcinoma (HCC) who underwent hepatectomy. PATIENTS AND METHODS: A total of 92 patients over 75 years old who underwent hepatectomy were enrolled in this study. Frailty was defined as clinical frailty scale (CFS) ≥ 4. Patients were divided into two groups, i.e., frailty group (n = 21) and no-frailty group (n = 71), and clinicopathological features were compared between them. RESULTS: The frailty group showed significant higher PIVKA-II level and larger tumor diameter (p < 0.05). CRP level and modified Glasgow prognostic score were significantly higher in the frailty group (p < 0.05). The frailty group showed higher rate of postoperative complications of Clavien-Dindo III (p = 0.06) and longer postoperative stay (p = 0.08). Cancer-specific, overall, and disease-free survival rates were significantly worse in the frailty group (p < 0.05). Frailty was detected as an independent prognostic factor on multivariate analysis of cancer-specific survival. CONCLUSION: Frailty can estimate the prognosis of HCC patients who underwent hepatectomy.

Stromal tumor-infiltrating lymphocytes level as a prognostic factor for resected intrahepatic cholangiocarcinoma and its prediction by apparent diffusion coefficient.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are a prognostic factor or an indicator of chemotherapy response for various malignancies. The aim of this study was to investigate the prognostic impact of TILs in resected intrahepatic cholangiocarcinoma (IHCC). We also investigated the usefulness of the apparent diffusion coefficient (ADC) in diffusion-weighted magnetic resonance imaging (DW-MRI) to predict TILs. METHODS: We enrolled 23 patients with IHCC who underwent initial hepatic resection in Tokushima University Hospital from 2006 to 2017. We evaluated stromal TILs in the tumor marginal area and central area in surgical specimens. Patients were divided into low vs high stromal TILs groups. We analyzed the patients' clinicopathological factors, including prognosis, according to the degree of stromal TILs. We also analyzed the correlation between stromal TILs and the minimum ADC value. RESULTS: Stromal TILs in the marginal area reflected overall survival more accurately than that in the central area. Additionally, marginal low TILs was significantly associated with lymph node metastasis and portal vein invasion. Both overall- and disease-free survival rates in the marginal low TILs group were significantly worse than those in the marginal high TILs group (P < 0.05). In the multivariate analysis, marginal low TILs were an independent prognostic factor for both overall- and disease-free survival (P < 0.05), and marginal low TILs were significantly associated with lower minimum ADC values (P < 0.02). CONCLUSIONS: Stromal TILs, especially in the marginal area, might demonstrate prognostic impact in patients with IHCC. Moreover, the ADC values from MRI may predict TILs in IHCC tumor tissue.

Significance of frailty in prognosis after surgery in patients with pancreatic ductal adenocarcinoma.

BACKGROUND: Frailty is an important consideration for older patients undergoing surgery. We aimed to investigate whether frailty could be a prognostic factor in patients with pancreatic ductal adenocarcinoma who underwent pancreatic resection. METHODS: One hundred and twenty patients who underwent pancreatic resection for pancreatic ductal adenocarcinoma were enrolled. Frailty was defined as a clinical frailty scale score ≥4. Patients were divided into frailty (n = 29) and non-frailty (n=91) groups, and clinicopathological factors were compared between the two groups. RESULTS: The frailty group showed an older age, lower serum albumin concentration, lower prognostic nutritional index, larger tumor diameter, and higher rate of lymph node metastasis than the non-frailty group (p < 0.05). Neutrophil-lymphocyte ratio and modified Glasgow prognostic score tended to be higher in the frailty group. Cancer-specific and disease-free survival rates were significantly poor in the frailty group (p < 0.05). With a multivariate analysis, frailty was an independent prognostic factor of cancer-specific survival. CONCLUSIONS: Frailty can predict the prognosis of patients with pancreatic ductal adenocarcinoma who undergo pancreatic resection.

A new pathological classification of intrahepatic cholangiocarcinoma according to protein expression of SSTR2 and Bcl2.

BACKGROUND: No universal classification method for intrahepatic cholangiocarcinoma (IHCC) has been reported based on the embryological origin of biliary epithelial cells. The aim of this study was to classify IHCC according to protein expression levels of somatostatin receptor 2 (SSTR2) and b-cell leukemia/lymphoma 2 (Bcl2) and to elucidate the clinicopathological features of each group. METHODS: Fifty-two IHCC patients who underwent hepatic resection were enrolled in this study. Protein expression levels of SSTR2 and Bcl2 were examined using immunohistochemistry. Clinicopathological factors were compared between the three groups and prognostic factors were investigated. RESULTS: The patients were divided into three groups: SSTR2 positive and Bcl2 negative (p-Group H, n = 21), SSTR2 negative and Bcl2 positive (p-Group P, n = 14), and the indeterminate group (p-Group U, n = 17) for cases where SSTR2 and Bcl2 were both positive or both negative. All p-Group P cases displayed curability A or B. The 5-year survival rates of p-Group H and U patients were worse than those in p-Group P. p-Group H had higher T-factor, clinical stage, and incidence of periductal infiltration than p-Group P. CONCLUSIONS: This method could be used to classify IHCC into peripheral and perihilar type by embryological expression patterns of SSTR2 and Bcl2.

Preoperative lymphocyte/C-reactive protein ratio and its correlation with CD8+ tumor-infiltrating lymphocytes as a predictor of prognosis after resection of intrahepatic cholangiocarcinoma.

PURPOSE: To clarify whether the preoperative lymphocyte/C-reactive protein (CRP) ratio (LCR) is a prognostic factor for patients with intrahepatic cholangiocarcinoma (IHCC), and investigate its mechanism via tumor-infiltrating lymphocytes. METHODS: The subjects of this retrospective study were 42 patients who had undergone hepatectomy for IHCC. We divided the patients into low LCR and high LCR groups (cutoff value: 8780) and analyzed their overall survival (OS) and disease-free survival (DFS) with respect to LCR and other clinicopathological factors. We also investigated the levels of stromal tumor-infiltrating lymphocytes (TILs) and CD8+ TILs in surgical specimens, and the relationship between LCR and TILs. RESULTS: A low LCR was identified in 21 patients and was significantly correlated with older age, a high CRP-albumin ratio, and advanced disease stage, and was a prognostic factor for OS and DFS. Multivariate analysis revealed that a low LCR was an independent prognostic factor for worse OS (HR 10.40, P = 0.0077). Although the LCR and levels of stromal TILs were not significantly related, LCR and levels of CD8+ TILs were significantly related (P = 0.0297). CONCLUSION: The preoperative LCR may predict the postsurgical prognosis of patients with IHCC and reflect the CD8+ TILs.

Utility of cone unit liver resection for small hepatocellular carcinoma: a propensity score matched analysis.

BACKGROUND: Anatomical resection (AR) is performed widely for hepatocellular carcinoma (HCC). However, it is controversial whether typical AR, which removes the whole feeding territory of the tumor-bearing portal branch bordered by the landmark veins, is necessary. The aim of this study was to investigate the utility of small AR, so-called cone unit resection, for small HCC. METHODS: Between 2007 and 2019, 372 hepatectomies were performed for HCC. Among them, 91 initial resections for small (<5 cm) solitary HCC were performed by typical AR (n = 44) or cone unit AR (n = 47). Propensity score matching was performed and clinicopathological features including prognosis were compared. RESULTS: At baseline, platelet count was higher, and liver function (serum albumin level) and indocyanine green retention at 15 min were better in the typical AR than cone unit AR group. There was no significant difference between the typical AR and cone unit AR group for tumor characteristics, short- and long-term outcomes. Even after propensity score matching (n = 29), the short- and long-term outcomes were also equivalent in between the two groups. CONCLUSION: There was no difference in prognosis of typical and cone unit AR. Therefore, cone unit AR is a feasible procedure for small HCC.

Intraoperative 3D Hologram Support With Mixed Reality Techniques in Liver Surgery.

OBJECTIVE: The aim of this study was to investigate the potential of an intraoperative 3D hologram, which was a computer graphics model liver, with mixed reality techniques in liver surgery. SUMMARY BACKGROUND DATA: The merits for the application of a hologram for surgical support are: 1) no sterilized display monitor; 2) better spatial awareness; and 3) 3D images shared by all the surgeons. METHODS: 3D polygon data using preoperative computed tomography data was installed into head mount displays, HoloLens (Microsoft Corporation, Redmond, WA). RESULTS: In a Wi-Fi-enabled operative room, several surgeons wearing HoloLens succeeded in sharing the same hologram and moving that hologram from respective operators' angles by means of easy gesture-handling without any monitors. The intraoperative hologram contributed to better imagination of tumor locations, and for determining the parenchymal dissection line in the hepatectomy for the patients with more than 20 multiple colo-rectal liver metastases. In another case, the hologram enabled a safe Gliisonean pedicle approach for hepato-cellular carcinoma with a hilar anatomical anomaly. Surgeons could easily compare the real patient's anatomy and that of the hologram just before the hepatic hilar procedure. CONCLUSIONS: This initial experience suggested that an intraoperative hologram with mixed reality techniques contributed to "last-minute simulation," not for "navigation." The intraoperative hologram might be a new next-generation operation-supportive tool in terms of spatial awareness, sharing, and simplicity.

De novo hepatocellular carcinoma in living donor liver grafts: A Japanese multicenter experience.

AIM: Direct-acting antivirals for hepatitis C virus have reduced the decompensation risk. Immunosuppressants for transplantation raise the risk of occurrence of de novo malignancies. We assessed the probabilities of and risk factors for de novo hepatocellular carcinoma (HCC) development post-living donor liver transplantation (LDLT). METHODS: We retrospectively evaluated the data of developed HCC in a graft including metastatic HCC post-LDLT from 2779 adult cases collected from nine major liver transplantation centers in Japan. RESULTS: Of 2779 LDLT adult recipients, 34 (1.2%) developed HCCs in their grafts. Of 34, five HCCs appeared to be de novo because of a longer period to tumor detection (9.7 [6.4-15.4] years) and no HCC within the native liver of the two recipients. The donor origin of three of five de novo HCCs was confirmed using microsatellite analysis in resected tissue. Primary disease of all five was hepatitis C virus-related cirrhosis, of which two were treated with direct-acting antivirals. Four of five developed HCC de novo in the hepatitis B core antibody-positive grafts. De novo HCCs had favorable prognosis; four of five were cured with complete remission. However, recurrent HCC (n = 29) in the graft had a poorer outcome, especially in patients with neutrophil to lymphocyte ratio scores above 4 (median survival time, 262 [19-463] days). CONCLUSION: Analysis of the database from major liver transplantation institutes in Japan revealed that de novo HCCs determined by microsatellite analysis were rarely detected, but the majority were successfully treated. LDLT recipients with higher risks of de novo HCC, including those with hepatitis B core antibody-positive grafts, should be carefully followed by surveillance of the liver graft.

Role of Central Hypo-enhancement in the Hepatic Arterial Phase of Dynamic Computed Tomography in Patients with Mass-Forming Intrahepatic Cholangiocarcinoma.

BACKGROUND/PURPOSE: The enhancement pattern in the hepatic arterial phase (HAP) of dynamic computed tomography (CT) is reportedly a prognostic marker in patients with intrahepatic cholangiocarcinoma (IHCC). This study was performed to clarify the significance of central hypo-enhancement in the HAP in patients with mass-forming IHCC. METHODS: Forty patients who had undergone initial surgical resection for mass-forming IHCC were enrolled. The dynamic CT was scanned 40 s after contrast agent injection as the HAP. A radiologist classified the patients into three groups based on the vascular pattern: the hyper-enhancement group (Hyper group), rim-enhancement group (Rim group), and hypo-enhancement group (Hypo group). The surgical specimens were immunohistochemically stained for hypoxia-inducible factor 1 (HIF-1). The correlation with clinicopathological findings and HIF-1 expression was investigated. RESULTS: The Hyper, Rim, and Hypo groups comprised 8, 7, and 25 patients, respectively. There were no significant correlations between the groups and clinicopathological factors. Overall survival (OS) was significantly worse in the Hypo than in the Hyper group (p = 0.03). OS was also significantly worse in the Rim + Hypo group (i.e., hypo-enhancement in the central tumor) than in the Hyper group (p = 0.04). Furthermore, inclusion in the Rim + Hypo group was a prognostic factor for OS (hazard ratio 6.68). High HIF-1 expression in the central part of the tumor was correlated with central hypo-enhancement (Hyper group: 25% and Rim + Hypo group: 72%). CONCLUSIONS: Central hypo-enhancement was a prognostic factor in patients with IHCC. The high malignant potential of tumors with central hypo-enhancement might be associated with HIF-1 upregulation.

Effectiveness of repeat surgery for recurrence after primary hepatectomy in patients with intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (IHCC) has a poor prognosis, and surgery remains the only effective treatment. However, tumor recurrence after primary hepatectomy is common. We examined the significance of repeat surgery for IHCC. METHODS: We collected data for all patients with IHCC between 1992 and 2018 (n = 67) in our database. Fifty-three (79.1%) of all 67 patients experienced recurrence after primary hepatectomy and we analyzed data for those 53 recurrent patients. We divided recurrent patients into a repeat surgery group (n = 9), chemotherapy group (n = 19), and best supportive care group (n = 25). We analyzed differences in patients' clinicopathological factors, including prognosis, between the three groups. RESULTS: The IHCC recurrence rate after hepatectomy in our institution was 79.1%. Of the 53 patients with recurrence, nine underwent repeat surgery (17.0%). The characteristics of the patients undergoing repeat surgery was lower stage at primary hepatectomy. Recurrence sites in the repeat surgery group were liver (n = 6), lung (n = 2), and adrenal gland (n = 1), as a single nodule. The period between primary hepatectomy and recurrence was comparatively longer in the repeat surgery group, at 1.8 years. The prognosis in patients undergoing repeat surgery was significantly better compared with the other groups. Not undergoing repeat surgery (hazard ratio: 5.506; p = 0.0077) and positive lymph node metastasis (hazard ratio: 2.207; p = 0.0242) were independent poor prognostic factors. CONCLUSIONS: Repeat surgery should be considered in patients with IHCC with a single recurrence site and negative lymph node metastasis at primary surgery and at least more than 6 months of disease-free period after primary surgery.

HIF-1α expression in liver metastasis but not primary colorectal cancer is associated with prognosis of patients with colorectal liver metastasis.

BACKGROUND: The role of hypoxia-inducible factor-1α (HIF-1α) in primary colorectal cancer (CRC) and colorectal liver metastasis (CRLM) has remained unclear. The aim of this study was to investigate HIF-1α expression and its association with prognosis in patients with CRLM with a focus on hepatic stellate cells (HSCs). METHODS: Colon cancer cells were cultured in HSC-conditioned medium (CM), and HIF-1α expression and cell migration were analyzed. Seventy-five patients with CRLM who underwent an initial curative hepatectomy were enrolled. We examined HIF-1α expressions and patient prognosis between primary CRCs and the matched liver metastatic specimens. RESULTS: Activated HSCs induced HIF-1α mRNA and protein expression in colon cancer cells (p < 0.01) and promoted cell migration (p < 0.01). The positive rates of HIF-1α expression in primary CRCs and liver metastases were 68.0 and 72.0%, respectively. There were no differences in overall (OS) and disease-free survival (DFS) of HIF-1α expression in primary CRC. However, HIF-1α expression in liver metastasis correlated to poor prognosis in both OS and DFS. Furthermore, patients with HIF-1α positive expression in liver metastasis had poor prognosis. CONCLUSION: HIF-1α expression in liver metastasis determines poor prognosis of CRLM patients. HSCs might play a key role in aggressive phenotypes of tumor cells.

The protective effect of epigallocatechin 3-gallate on mouse pancreatic islets via the Nrf2 pathway.

PURPOSE: Epigallocatechin 3-gallate (EGCG), a green tea polyphenol, has been shown to have anti-oxidant and anti-inflammatory effects in vitro and in vivo. The aim of this study was to investigate the effects and mechanism of EGCG on isolated pancreatic islets as pre-conditioning for pancreatic islet transplantation. METHODS: The pancreatic islets were divided into two groups: an islet culture medium group (control) and an islet culture medium with EGCG (100 µM) group. We investigated the islet viability, Nrf2 expression, reactive oxygen species (ROS) production, and heme oxygenase-1 (HO-1) mRNA. Five hundred islet equivalents after 12 h of culture for the EGCG 100 µM and control group were transplanted under the kidney capsule of streptozotocin-induced diabetic ICR mice. RESULTS: The cell viability and insulin secretion ability in the EGCG group were preserved, and the nuclear translocation of Nrf2 was increased in the EGCG group (p < 0.01). While the HO-1 mRNA levels were also higher in the EGCG group than in the control group (p < 0.05), the ROS production was lower (p < 0.01). An in vivo functional assessment showed that the blood glucose level had decreased in the EGCG group after transplantation (p < 0.01). CONCLUSION: EGCG protects the viability and function of islets by suppressing ROS production via the Nrf2 pathway.

Nab-paclitaxel interrupts cancer-stromal interaction through C-X-C motif chemokine 10-mediated interleukin-6 downregulation in vitro.

Cancer-associated fibroblasts (CAF), derived from stroma of cancer tissues, interact with cancer cells and play an important role in cancer initiation, growth, and metastasis. Nab-paclitaxel (nab-PTX) is a 130 nm albumin-binding paclitaxel and recommended for many types of cancer chemotherapy. The nab-PTX stromal-disrupting effect during pancreatic cancer treatment has been reported. The aim of the present study was to determine the role of nab-PTX in cancer cells and CAF interaction. Cancer cells (MIA PaCa-2 and Panc-1) were cocultured with CAF or treated with CAF conditioned medium, after which their migration and invasion ability, epithelial-mesenchymal transition (EMT)-related marker expression and C-X-C motif chemokine 10 (CXCL10) expression and secretion were detected. Nab-PTX treatment was carried out during the coculture system or during preparation of CAF conditioned medium. Then cancer cell migration and invasion ability, EMT-related marker expression, CXCL10 expression and secretion, and interleukin-6 (IL-6) expression and secretion by CAF were checked After coculture with CAF, migration and invasion ability of cancer cells increased. CAF also downregulated E-cadherin and upregulated N-cadherin and vimentin expression in cancer cells. During coculture or stimulation with cancer cell-cultured medium, CAF significantly increased IL-6 expression and secretion. However, nab-PTX in the coculture system canceled CAF-induced migration and invasion promotion and EMT-related gene changes. Moreover, nab-PTX increased CXCL10 expression of cancer cells which blocked CAF IL-6 expression and secretion. Nab-PTX treatment could increase CXCL10 expression of cancer cells which blocks CAF cancer cell migration and invasion-promoting effect by inhibiting IL-6 expression.

Nrf2 activation drive macrophages polarization and cancer cell epithelial-mesenchymal transition during interaction.

BACKGROUND: The M2 phenotype of tumor-associated macrophages (TAM) inhibits the anti-tumor inflammation, increases angiogenesis and promotes tumor progression. The transcription factor Nuclear Factor (erythroid-derived 2)-Like 2 (Nrf2) not only modulates the angiogenesis but also plays the anti-inflammatory role through inhibiting pro-inflammatory cytokines expression; however, the role of Nrf2 in the cancer cell and macrophages interaction is not clear. METHODS: Hepatocellular carcinoma cells (Hep G2 and Huh 7) and pancreatic cancer cells (SUIT2 and Panc-1) were co-cultured with monocytes cells (THP-1) or peripheral blood monocytes derived macrophages, then the phenotype changes of macrophages and epithelial-mesenchymal transition of cancer cells were detected. Also, the role of Nrf2 in cancer cells and macrophages interaction were investigated. RESULTS: In this study, we found that cancer cells could induce an M2-like macrophage characterized by up-regulation of CD163 and Arg1, and down-regulation of IL-1b and IL-6 through Nrf2 activation. Also, Nrf2 activation of macrophages promoted VEGF expression. The Nrf2 activation of macrophages correlated with the reactive oxygen species induced by cancer cells derived lactate. Cancer cells educated macrophages could activate Nrf2 of the cancer cells, in turn, to increase cancer cells epithelial-mesenchymal transition (EMT) through paracrine VEGF. These findings suggested that Nrf2 played the important role in the cancer cells and macrophages interaction. CONCLUSIONS: Macrophage Nrf2 activation by cancer cell-derived lactate skews macrophages polarization towards an M2-like phenotype and educated macrophages activate Nrf2 of the cancer cells to promote EMT of cancer cells. This study provides a new understanding of the role of Nrf2 in the cancer cell and TAM interaction and suggests a potential therapeutic target.

Photobiomodulation with red light-emitting diodes accelerates hepatocyte proliferation through reactive oxygen species/extracellular signal-regulated kinase pathway.

AIM: Cell-based transplantation is an alternate method of liver transplantation to delay the onset of end-stage liver diseases. For successful treatment, cells need to be expended in vitro expeditiously. However, autogenetic hepatocytes as the ideal cell source for therapy remain in quiescence so proliferation is rare. Photobiomodulation therapy has been used to stimulate some kinds of cell proliferation, but is unknown whether red light-emitting diode (LED) irradiation can promote primary hepatocyte proliferation. The aim of this study was to evaluate the effect of red LED irradiation on hepatocytes in vitro. METHODS: Mouse primary hepatocytes were isolated and received red LED treatment. The cell viability, reactive oxygen species (ROS) levels, phosphorylated extracellular signal-regulated kinase1/2 (pERK1/2) and some cell cycle-related proteins were observed. Additionally, ROS inhibition and pERK1/2 inhibition were carried out to determine the effect of ROS and ERK1/2 in red LED irradiation. RESULTS: The red LED irradiation increased hepatocyte proliferation, elevated intracellular ROS levels, and stimulated ERK1/2 activation and cell cycle-related gene expression. The mitosis promoting effect of red LED irradiation could be disturbed by ROS or pERK inhibition. The red LED irradiation promoted hepatocyte proliferation through the ROS/pERK1/2 pathway. CONCLUSIONS: Red LED irradiation could accelerate hepatocyte proliferation through the ROS/pERK1/2 pathway. Red LED irradiation might be a potential method to increase hepatocyte cell numbers in vitro and support cell-based transplantation in clinical work.

Role of heat shock factor 1 expression in the microenvironment of intrahepatic cholangiocarcinomas.

BACKGROUND AND AIM: Heat shock factor 1 (HSF1), a master regulator of heat shock response, has been shown to play a multifaceted role in cancer progression. However, the clinical significance and biological effect of HSF1 expression in intrahepatic cholangiocarcinoma (IHCC) remain unknown. METHODS: Forty-nine patients with IHCC who underwent hepatic resection were enrolled in this study. HSF1 expression in tumor tissue was determined by immunohistochemistry, and patients were divided into two groups, those with high (n = 20) and low (n = 29) HSF1 expression. Clinicopathological factors including prognosis were compared in these two groups. RESULTS: HSF1 expression was significantly higher in tumors than in normal tissue. The overall survival rate was significantly lower in patients with high than low HSF1. Multivariate analysis showed that high HSF1 expression was a factor independently prognostic of patient survival. CONCLUSION: High HSF1 expression in tumor tissues may be a prognostic biomarker in patients with IHCC.

Potential predictive factors for microvascular invasion in hepatocellular carcinoma classified within the Milan criteria.

BACKGROUND: Microvascular invasion (mvi) is an important risk factor for recurrent hepatocellular carcinoma (HCC), even after curative liver resection or orthotopic liver transplantation. However, mvi is difficult to detect preoperatively. The aim of this study was to clarify the risk factors of postoperative recurrence and investigate predictive factors of mvi before hepatectomy for HCC classified within the Milan criteria. METHODS: One hundred fifty-nine patients with hepatocellular carcinoma (HCC) classified within the Milan criteria, who underwent hepatectomy, were enrolled in this study. We investigated the risk factors of recurrence. In addition, we divided them into two groups: mvi-negative group and mvi-positive group, based on pathological findings after surgery. We compared the clinicopathological factors between the two groups and determined the risk factors for mvi. RESULTS: Overall survival rate at 1, 3, and 5 years were 91.6%, 80.5%, and 74.9%, and the recurrence-free survival rate at 1, 3, and 5-years were 72.3%, 51.6%, and 37.2%. Risk factor analysis for tumor recurrence revealed that total bilirubin, albumin, ICGR15, AFP-L3, tumor number, mvi, and tumor stage had a significant predictive value. Multivariate analysis revealed that tumor number and mvi were significant independent risk factors for tumor recurrence. Predictive analysis for risk factors of mvi revealed that multiple tumors and AFP-L3 > 10% were significant independent risk factors for mvi in HCC classified within the Milan criteria. CONCLUSIONS: The mvi was one of the independent risk factors for tumor recurrence in HCC classified within the Milan criteria. Multiple tumors and high AFP-L3 value were independent predictive factors for mvi.

Effective stepwise training and procedure standardization for young surgeons to perform laparoscopic left hepatectomy.

BACKGROUND: Laparoscopic hepatectomy remains one of the most difficult procedures for young surgeons to perform. We recently developed a new training method and standardization procedure for teaching young surgeons to perform laparoscopic left hepatectomy (Lap-LHx). The aim of this study was to assess the effectiveness of our method. METHODS: In 2004, we standardized a laparoscopic procedure for Lap-LHx, using a laparoscopy-assisted method as a stepping stone. The laparoscopic training method comprised the following three steps: (1) training in fundamental procedures using a dry box and checking by mentors; (2) detailed preoperative simulation using Vincent three-dimensional software for each patient; and (3) self-assessment including understanding of relevant anatomy and completion grade for each procedure using a check sheet and feedback by both mentors and a professor. Twenty-three Lap-LHx procedures performed during the study period were divided into two groups: those performed by young non-board-certified surgeons (n = 9) and those performed by senior board-certified surgeons (n = 14). RESULTS: The blood loss and operative time were similar in the young surgeon (194 g and 336 min, respectively) and senior surgeon groups (208 g and 322 min, respectively). CONCLUSION: Our standardized Lap-LHx procedure and stepwise training to perform it enable young surgeons to perform Lap-LHx as confidently and safely as more experienced surgeons.

Liver regeneration after splenectomy in patients with liver cirrhosis.

AIM: Splenectomy is a well-known procedure to improve thrombocytopenia and liver function in patients with liver cirrhosis (LC). However, the effect of splenectomy on liver regeneration remains unclear. The aim of this study is to investigate the effect of splenectomy on liver regeneration. METHODS: Twenty patients with LC who underwent splenectomy were included in this study. Liver and splenic volumes were measured by a 3-D simulation imaging system. Liver volume (LV) and clinicopathological data were compared before and 6 months after splenectomy. Thereafter, patients were divided into two groups: the elevated LV group and the reduced LV group. Patient characteristics were compared between the two groups. RESULTS: Postoperative LV was increased in 14 patients compared with the preoperative state. Thrombocytopenia, leukopenia, total bilirubin and prothrombin time were improved after splenectomy. In the elevated LV group, four patients exhibited improved Child-Pugh grades after splenectomy, whereas no patients demonstrated improvement in the reduced LV group. The elevated LV group exhibited high albumin level, good indocyanine green retention rate at 15 min and large splenic volume compared with the same measurements in the decreased group. Patients with larger spleen volumes and higher albumin values before splenectomy showed increased rates of LV after splenectomy. CONCLUSION: Splenectomy for patients with LC improved pancytopenia and liver function. Especially, in patients with large spleen and high albumin levels, considerable increases in LV and improved liver function were observed.