Impact of tumor shrinkage pattern with biweekly triplet gemcitabine+cisplatin+S-1 regimen for biliary tract cancers: Implications for neoadjuvant therapy from the data of KHBO1401 (KHBO1401-1A study).

BACKGROUND: The multicenter randomized phase III KHBO1401 study (gemcitabine+cisplatin+S-1 [GCS] versus GC in biliary tract cancers [BTC]) demonstrated that GCS not only prolonged patient survival but also achieved a high response rate and that it should be good for neoadjuvant therapy. Therefore, to explore the possibilities of neoadjuvant therapy, we investigated the tumor shrinkage pattern. METHODS: Among the total of 246 patients enrolled in the KHBO1401, the tumor shrinkage pattern and survival were investigated in patients with measurable BTC (n=183, 74%; GCS, n=91; GC, n=92). RESULTS: The tumor shrinkage pattern could be divided to 4 categories based on the response at 100 days after enrollment: category A (<-30% in size), B (-30% to 0%), C (0% to +20%), and D (>+20%). The GCS arm included more category A and B cases (61 [67%] vs. 33 [36%], P<0.0001). Each category predicted best response and overall survival (P<0.0001). Category A showed sustained tumor response compared with category B; in GCS, the time to maximum tumor response was 165 ± 76 days in category A and 139 ± 78 in category B. Categories C and D did not achieve tumor shrinkage. The maximum tumor shrinkage size in category A was -53% in the GCS arm and -65% in the GC arm (P=0.0892). Twenty percent of patients in the GCS showed tumor regrowth 154 ± 143 days later. CONCLUSION: GCS provided faster and greater tumor shrinkage with better survival in comparison to GC, although 20% of patients showed re-growth after 6 cycles.

Lymphaticovenous anastomosis for treatment of refractory chylous ascites: A case report.

Chylous ascites, the leakage of lymphatic fluid into the abdominal cavity caused by lymphatic fluid stasis or lymphatic vessel damage, can be treated by lymphaticovenous anastomosis (LVA). We report rarely performed abdominal LVA to treat a case of refractory ascites possibly caused by ligation of the thoracic duct and pleurodesis in a man aged 60 years requiring weekly ascites drainage. Ligation was abandoned because the leakage site was not determined. The greater omentum (GO) was generally edematous and showed lymphatic effusion by gross appearance, and was considered suitable for LVA. We performed once LVA in the lymphatic vessels and veins of the GO using common microsurgical instrumentation and lateral anastomosis. Lymphatic vessels in the omentum were dilated to 2-3 mm, and LVA was simple. After LVA, GO edema improved. Postoperatively, the patient developed paralytic ileus, which improved within a few days, and the patient was discharged without any increase in ascites after starting to diet. One year post-surgery, there was no recurrence of ascites. LVA at the GO may be effective for the treatment of refractory chylous ascites because of its absorptive lymphatic draining capabilities and large transverse vessels.

Hepatectomy is Beneficial in Select Patients with Multiple Hepatocellular Carcinomas.

BACKGROUND: A single hepatocellular carcinoma (HCC) is a good indication for hepatic resection regardless of tumor size, but the surgical indications for cases with multiple HCCs remain unclear. METHODS: We retrospectively reviewed the outcomes of hepatectomies for Barcelona Clinic Liver Cancer (BCLC) stage 0, A, and B HCCs. We further subclassified stage A and B into A1 (single nodule <5 cm, or three or fewer nodules ≤3 cm), A2 (single nodule 5-10 cm), A3 (single nodule ≥10 cm), B1 (two to three nodules >3 cm), and B2 (four or more nodules). RESULTS: A total of 1088 patients were enrolled, comprising 88 stage 0, 750 stage A (A1: 485; A2: 190; A3: 75), and 250 stage B (B1: 166; B2: 84) cases. The 5-year overall survival (OS) rates for stage 0, A1, A2, A3, B1, and B2 patients were 70.4%, 74.2%, 63.8%, 47.7%, 47.5%, and 31.9%, respectively (p < 0.0001). Significant differences in OS were found between stages A1 and A2 (p = 0.0118), A2 and A3 (p = 0.0013), and B1 and B2 (p = 0.0050), but not between stages A3 and B1 (p = 0.4742). In stage B1 patients, multivariate analysis indicated that Child-Pugh B cirrhosis was the only independent prognostic factor for the OS outcome. CONCLUSIONS: A hepatectomy should be considered for multiple HCCs if the number of tumors is three or fewer, especially in patients with no cirrhosis or in Child-Pugh A cases, because the long-term results are equivalent to those for a single HCC.

Central Hepatectomy Versus Major Hepatectomy for Centrally Located Hepatocellular Carcinoma: A Propensity Score Matching Study.

BACKGROUND: In terms of anatomical liver sectionectomy approaches, both a central hepatectomy (CH) and major hepatectomy (MH) are feasible options for a centrally located hepatocellular carcinoma (HCC). METHODS: We retrospectively reviewed the surgical outcomes of central HCC patients who underwent CH or MH. MH includes hemihepatectomy or trisectionectomy, whereas CH involves a left medial sectionectomy, right anterior sectionectomy, or central bisectionectomy. The surgical outcomes were compared before and after propensity score matching (PSM). RESULTS: A total of 233 patients were enrolled, including 132 in the CH group and 101 in the MH group. The MH group cases were pathologically more advanced and had poorer overall survival rates than the CH group. After PSM, 68 patients were selected into each group, both of which showed similar overall and recurrence-free survival outcomes. The CH group showed a tendency for a longer operation time; however, other perioperative outcomes were similar between the two groups. Multivariate analyses of our matched HCC patients revealed that the type of surgery (CH or MH) was not an independent prognostic factor. More patients in the matched CH group experienced a repeat hepatectomy for recurrence and no patients in this group underwent a preoperative portal vein embolization. CONCLUSIONS: The short- and long-term surgical outcomes of CH and MH for a centrally located HCC are similar under a matched clinicopathological background. CH has the advantage of not requiring a preoperative portal vein embolization and increased chances of conducting a repeat hepatectomy for recurrence.

Early administration of amatuximab, a chimeric high-affinity anti-mesothelin monoclonal antibody, suppresses liver metastasis of mesothelin-expressing pancreatic cancer cells and enhances gemcitabine sensitivity in a xenograft mouse model.

Amatuximab is a promising therapeutic antibody targeting mesothelin, a 40-kDa glycoprotein that is highly expressed in pancreatic cancer. We investigated the effectiveness of early amatuximab treatment, imitating an adjuvant chemotherapy setting, and combination therapy with amatuximab and gemcitabine in liver metastasis of pancreatic cancer. Liver metastasis mouse models were established in 8-week-old male BALB/c nu/nu mice using the hemisplenic injection method. Tridaily amatuximab monotherapy or combination with gemcitabine was administered to the liver metastasis mouse model before metastatic lesions had formed huge masses. Gaussia luciferase-transfected AsPC-1 was used as a mesothelin-overexpressing pancreatic cancer cell line. The amount of liver metastases and the serum luciferase activity were significantly lower in the treatment groups than those in the control IgG group. Notably, the anti-tumor activity of gemcitabine was synergically enhanced by combination therapy with amatuximab. Furthermore, western blotting revealed that the high expression of phosphorylated c-Met and AKT in liver metastatic lesions treated with gemcitabine monotherapy was canceled by its combination with amatuximab. This result indicated that the observed synergic therapeutic effect may have occurred as a result of the inhibitory effect of amatuximab on the phosphorylation of c-Met and AKT, which were promoted by exposure to GEM. In conclusion, our study revealed that early administration of amatuximab alone or in combination with GEM significantly suppressed the liver metastases of mesothelin-expressing pancreatic cancer cells. A phase II clinical trial of amatuximab as part of an adjuvant chemotherapy regimen for resected pancreatic cancer is expected.

Mesothelin blockage by Amatuximab suppresses cell invasiveness, enhances gemcitabine sensitivity and regulates cancer cell stemness in mesothelin-positive pancreatic cancer cells.

BACKGROUND: Mesothelin is a 40-kDa glycoprotein that is highly overexpressed in various types of cancers, however molecular mechanism of mesothelin has not been well-known. Amatuximab is a chimeric monoclonal IgG1/k antibody targeting mesothelin. We recently demonstrated that the combine therapy of Amatuximab and gemcitabine was effective for peritonitis of pancreatic cancer in mouse model. METHODS: We discover the role and potential mechanism of mesothelin blockage by Amatuximab in human pancreatic cells both expressing high or low level of mesothelin in vitro experiment and peritonitis mouse model of pancreatic cancer. RESULTS: Mesothelin blockage by Amatuximab lead to suppression of invasiveness and migration capacity in AsPC-1 and Capan-2 (high mesothelin expression) and reduce levels of pMET expression. The combination of Amatuximab and gemcitabine suppressed proliferation of AsPC-1 and Capan-2 more strongly than gemcitabine alone. These phenomena were not observed in Panc-1 and MIA Paca-2 (Mesothelin low expression). We previously demonstrated that Amatuximab reduced the peritoneal mass in mouse AsPC-1 peritonitis model and induced sherbet-like cancer cell aggregates, which were vanished by gemcitabine. In this study, we showed that the cancer stem cell related molecule such as ALDH1, CD44, c-MET, as well as proliferation related molecules, were suppressed in sherbet-like aggregates, but once sherbet-like aggregates attached to peritoneum, they expressed these molecules strongly without the morphological changes. CONCLUSIONS: Our work suggested that Amatuximab inhibits the adhesion of cancer cells to peritoneum and suppresses the stemness and viability of those, that lead to enhance the sensitivity for gemcitabine.

Diagnostic timing dependent characteristics of acute kidney injury following hepatectomy: a retrospective historical cohort analysis.

BACKGROUND: The timing of diagnosis of post-hepatectomy acute kidney injury (AKI) has rarely been investigated. The aim of this retrospective study was to reveal the differences between AKI subtypes following hepatectomy, as classified by timing of diagnosis. METHOD: Post-hepatectomy AKI was classified as very transient AKI (vtAKI; criteria satisfied by the serum creatinine value immediately after surgery) or non-transient AKI (ntAKI; all other AKI types except for vtAKI). Multivariate logistic regression analyses for both AKI types were performed separately to identify differences in known perioperative AKI risk factors. The impacts of each AKI subtype on postoperative complications, hospital stay and renal outcome at discharge were also evaluated. RESULTS: AKI was diagnosed in 135 of 750 patients (18.0%); 82 and 53 patients were classified as vtAKI and ntAKI, respectively. In multivariate analysis, even among the perioperative factors associated with whole AKI, there were distinct relationships depending on vtAKI or ntAKI. Furthermore, only ntAKI was associated with postoperative complications, longer hospital stays and impaired renal function at discharge. CONCLUSIONS: Based on the results of this study, future post-hepatectomy AKI studies should only include ntAKI and exclude vtAKI, as vtAKI has minimal clinical impact despite accounting for a significant proportion of AKI patients. CLINICAL TRIAL REGISTRATIONS: None.

Hepatectomy Combined with Diaphragmatic Resection for Hepatocellular Carcinoma with Diaphragmatic Involvement: A Propensity Score-Matched Analysis.

PURPOSE: We evaluated the short- and long-term surgical outcomes of hepatectomy combined with diaphragmatic resection for hepatocellular carcinoma (HCC) with diaphragmatic involvement. METHODS: We retrospectively reviewed the surgical outcomes of HCC patients with diaphragmatic resection (DR group) and HCC patients without diaphragmatic resection (non-DR group). We applied 1:1 propensity score matching (PSM) to these subjects. RESULTS: The study included 46 patients in DR group and 828 patients in non-DR group. The DR group cases were pathologically more advanced, and both overall and relapse-free survival among the patients in this group with pathological diaphragmatic invasion were similar to cases with pathological diaphragmatic fibrous adhesion. There were 40 patients from each group subjected to PSM. In these matched cohorts, there was no statistically significant difference between the two groups regarding perioperative outcomes, overall survival, and relapse-free survival. Multivariate analyses of our matched HCC patients revealed that alpha-fetoprotein expression and tumor size were independent prognostic factors for overall survival and poor differentiation for relapse-free survival, whereas neither diaphragmatic invasion nor diaphragmatic resection were prognostic indicators. The most frequent site of recurrence in non-DR group was the liver, whereas the most frequent site of recurrence in DR group was the lung before and after PSM. CONCLUSIONS: The short- and long-term surgical outcomes of DR HCC cases are equivalent to their non-DR counterparts under a matched clinicopathological background. Hepatectomy combined with DR is an acceptable treatment for HCC with either diaphragmatic fibrous adhesion or diaphragmatic invasion.

Long-term prognostic factors of patients with hepatocellular carcinoma who survive over 10 years after hepatectomy.

BACKGROUND AND OBJECTIVES: The aim was to evaluate long-term prognostic factors in hepatocellular carcinoma (HCC) patients who survived over 10 years after hepatectomy and compare prognostic factors between patients with recurrence who died and survived 10 years after initial hepatectomy. METHODS: We analyzed the HCC patients without recurrence over 10 years after hepatectomy (n = 35), those with recurrence who survived over 10 years (n = 48), and those who died within 10 years (n = 132). RESULTS: The rate of recurrence was 16.3%, 10-year overall survival rate was 38.6%, and the 10-year recurrence-free survival (RFS) rate was 16.7%. Nonviral, solitary tumor, well differentiation, and without severe fibrosis were independent favorable factors for long-term RFS. High cholinesterase levels, small tumors and without portal vein invasion were independent favorable factors for long-term survival among patients with recurrence. Long-term survivors with recurrence showed significantly low early recurrence, extrahepatic recurrence, multiple intrahepatic recurrences. CONCLUSION: Important factors for long-term prognoses in HCC patients were a solitary tumor, small tumors, and no advanced fibrosis. A treatment for nonviral hepatitis is needed to achieve long-term RFS. Even patients who relapse might survive long term if they have a late or solitary intrahepatic recurrence, nonsevere cirrhosis, and curative treatment at recurrence.

CD133 and epithelial cell adhesion molecule expressions in the cholangiocarcinoma component are prognostic factors for combined hepatocellular cholangiocarcinoma.

AIM: A new classification of combined hepatocellular cholangiocarcinoma (CHC) was recently reported. Cancer stem cells have been associated with CHC carcinogenesis. This study examined the association of cancer stem cell marker expression and prognosis in CHC classified using the new classification. METHODS: We enrolled 26 CHC patients and classified them according to the new classification. We evaluated the expression of cancer stem cell markers (CD56, CD133, and epithelial cell adhesion molecule [EpCAM]) by immunohistochemical staining in each component. We analyzed the association between expressions and prognosis. RESULTS: Seven cases were hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) (cHCC-CCA), 12 were HCC and intermediate cell carcinoma (HCC-INT), and seven were intermediate cell carcinoma (INT). The CD133-positive rate tended to be higher in the CCA (42.9%) and INT component (50.0%) than the HCC component (14.3%) in cHCC-CCA. In HCC-INT, the CD133-positive rate in the INT component (83.3%) was significantly higher than the HCC component (8.3%; P = 0.001). For EpCAM, the positive rate in the CCA component (71.4%) and INT component (50.0%) tended to be higher than the HCC component (14.3%) in cHCC-CCA. Overall survival and disease-free survival were significantly worse in cases with CD133-positive (P = 0.048 and P = 0.048, respectively) or EpCAM-positive (P = 0.041 and P = 0.041, respectively) CCA component in cHCC-CCA. CONCLUSIONS: INT and CCA components showed higher expression rates of cancer stem cell markers than the HCC component. CD133 or EpCAM expression in the CCA component was associated with poor prognosis in cHCC-CCA.

Prognoses, outcomes, and clinicopathological characteristics of very elderly patients with hepatocellular carcinoma who underwent hepatectomy.

OBJECTIVES: The aim was to evaluate the prognostic factors, clinicopathological characteristics, and surgical outcomes after hepatectomy in very elderly patients with hepatocellular carcinoma (HCC). METHODS: We analyzed 796 patients with HCC from 2000 to 2017. Patients aged 80 years or older were classified into the very elderly group (group VE; n = 49); patients younger than 80 years old and aged 65 years or older were classified into the elderly group (group E; n = 363), and patients younger than 65 years old were classified into the young group (group Y; n = 384). We investigated the prognoses, clinicopathological characteristics, and surgical outcomes after hepatectomy. RESULTS: The number of surgical procedures and outcomes, including morbidities, was not significantly different. Groups VE, E, and Y showed similar prognoses in terms of both survival and recurrence. In group VE, prothrombin activity (PA) < 80% and PIVKA-II ≥ 400 mAU/ml were unfavorable factors for survival, and PIVKA-II ≥ 400 mAU/ml and the presence of portal venous invasion (PVI), hepatic venous invasion, and fibrosis were unfavorable factors for recurrence. In group E, ChE < 180 IU/l, AFP ≥ 20 ng/ml, tumor size ≥ 10 cm, and the presence of multiple tumors, PVI, and hepatic venous invasion (HVI) were unfavorable factors for survival, and ChE < 180 IU/l, tumor size ≥ 10 cm, and the presence of multiple tumors, PVI, and HVI were unfavorable factors for recurrence. In group Y, AFP ≥ 20 ng/ml, the presence of multiple tumors, poor differentiation, PVI, HVI, and blood loss ≥ 400 ml were unfavorable factors for survival, and PA < 80%, albumin < 3.5 g/dl, AFP ≥ 20 ng/ml, tumor size ≥ 10 cm, and the presence of multiple tumors, poor differentiation, and PVI were unfavorable factors for recurrence. CONCLUSIONS: Tumor factors might have limited influence on the prognosis of very elderly patients, and liver function reserve might be important for the long-term survival of very elderly patients. Hepatectomy can be performed safely, even in very elderly patients. Hepatectomy should not be avoided in very elderly patients with HCC if patients have a good general status because these patients have the same prognoses as nonelderly individuals.

Prognostic impact of CD8+ T cell distribution and its association with the HLA class I expression in intrahepatic cholangiocarcinoma.

PURPOSE: A lack of effective systemic therapy is one reason for the poor prognosis of intrahepatic cholangiocarcinoma. Newly developed immune checkpoint inhibitors function by minimizing CD8+ T cell suppression to improve tumor-specific responses. This study aimed to examine the characteristics of CD8+ T cells in intrahepatic cholangiocarcinoma. METHODS: Clinicopathological data, including the overall survival, of 69 cases of postoperative intrahepatic cholangiocarcinoma were prospectively investigated. We then immunohistochemically stained for CD8, Foxp3, CD163, PD-L1, and human leukocyte antigen (HLA) class I and counted the number of CD8+ T cells, Foxp3+ T cells, and CD163+ macrophages in different areas (outer border, interborder, and intratumor). RESULTS: A significant difference was found in the 5-year overall survival between the CD8+ T cell high group (45.5%) and low group (24.7%) in the outer border area (p = 0.0103). Furthermore, the number of CD8+ T cells and the high expression of HLA class I were positively correlated (p = 0.0341). CONCLUSION: The number of CD8+ T cells in the outer border area of the tumor correlated with the HLA class I expression of intrahepatic cholangiocarcinoma and may therefore be a prognostic factor for patients with postoperative intrahepatic cholangiocarcinoma.

Clinical and pathological features of combined hepatocellular-cholangiocarcinoma compared with other liver cancers.

BACKGROUND AND AIM: Combined hepatocellular-cholangiocarcinoma (CHC) is a primary liver cancer containing both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) elements. Its reported clinicopathological features and prognoses have varied because of its low prevalence. This study aimed to clarify these aspects of CHC. METHODS: We enrolled 28 patients with CHC, 1050 with HCC, and 100 with ICC and compared the clinicopathological characteristics and prognosis of CHC with HCC and ICC. We also analyzed prognostic factors, recurrence patterns, and management in CHC patients. RESULTS: The incidences of hepatitis B virus and high α-fetoprotein and protein induced by vitamin K absence or antagonists-II levels were significantly higher among CHC compared with ICC patients. Multiple tumors were more frequent in CHC compared with the other groups, while vascular invasion and lymph node metastasis were more frequent in the CHC than the HCC group. The 5-year overall survival and disease-free survival rates for CHC were 25.1% and 22.6%, respectively. Overall survival was significantly lower than for HCC (P < 0.001) but not ICC (P = 0.152), while disease-free survival was significantly lower than for HCC and ICC (P = 0.008 and P = 0.005, respectively). Multivariate analysis identified carcinoembryonic antigen levels and tumor size as independent predictors in patients with CHC. CONCLUSIONS: The clinical features of CHC, including sex, hepatitis B virus infection, α-fetoprotein, and protein induced by vitamin K absence or antagonists-II levels, were similar to HCC, while its prognosis and pathological features, including vascular invasion and lymph node metastasis, were similar to ICC. Carcinoembryonic antigen levels and tumor size were independent prognostic factors in patients with CHC.

Prognoses and Clinicopathological Characteristics for Hepatocellular Carcinoma Originating from the Caudate Lobe After Surgery.

BACKGROUND: The aim was to evaluate the prognoses and clinicopathological characteristics of solitary hepatocellular carcinoma (HCC) originating from the caudate lobe (HCC-CL). METHODS: We analyzed 584 patients with a solitary tumor <10 cm from January 1990 to November 2014. Patients were classified into a caudate lobe group (CL; n = 39) and a non-caudate lobe group (NCL; n = 545). We investigated the prognoses and clinicopathological characteristics of solitary HCC-CL. We compared the surgical procedures performed in these cases. RESULTS: HCC-CL had a similar rate of portal venous invasion (PVI) as HCC-NCL (21% vs. 19%); however, the frequency of tumor thrombus at the first branch of the portal vein (PV) or extension to the trunk or the opposite side of the PV was significantly higher in HCC-CL (8% vs. 2%). HCC-CL had similar OS rates compared to HCC-NCL; however, HCC-CL showed significantly poorer RFS. Although there were no significant differences among the three surgical procedures, blood loss and complication rates tended to be higher in cases who underwent an isolated caudate lobectomy. Tumor size ≥5 cm, PVI, and liver fibrosis or cirrhosis (LF or LC) were independent unfavorable factors for both OS and RFS. PIVKA-II ≥120 mAU/ml was an independent unfavorable factor for RFS. CONCLUSION: HCC-CL presented a poorer RFS rate. Patients with a tumor size ≥5 cm, PIVKA-II ≥120 mAU/ml, portal venous invasion, and LF or LC should be diligently followed up as these cases have a high risk of recurrence.

Hepatic hypertrophy and hemodynamics of portal venous flow after percutaneous transhepatic portal embolization.

BACKGROUND: Percutaneous transhepatic portal embolization (PTPE) is useful for safe major hepatectomy. This study investigated the correlation between hepatic hypertrophy and hemodynamics of portal venous flow by ultrasound sonography after PTPE. METHODS: We analyzed 58 patients with PTPE, excluding those who underwent recanalization (n = 10). Using CT volumetry results 2 weeks after PTPE, the patients were stratified into a considerable hypertrophy group (CH; n = 15) with an increase rate of remnant liver volume (IR-RLV) ≥ 40% and a minimal hypertrophy group (MH; n = 33) with an IR-RLV < 40%. We investigated the hemodynamics of portal venous flow after PTPE and the favorable factors for hepatic hypertrophy. RESULTS: Univariate and multivariate analysis identified the indocyanine green retention rate at 15 min (ICGR15) and increase rate of portal venous flow volume (IR-pFV) at the non-embolized lobe on day 3 after PTPE as independent favorable factors of IR-RLV. Patients with IR-pFV on day 3 after PTPE ≥100% and ICGR15 ≤ 15% (n = 13) exhibited significantly increased IR-RLV compared with others (n = 35). CONCLUSIONS: Cases with high IR-pFV on day 3 after PTPE exhibited better hepatic hypertrophy. Preserved liver function and increased portal venous flow on day 3 were important.

Transparenchymal glissonean approach: a novel surgical technique for advanced perihilar bile duct cancer.

PURPOSE: To increase the surgical opportunities for locally advanced perihilar bile duct cancers that require left-sided hepatectomies, we developed the transparenchymal glissonean approach (TGA); it comprises intra-hepatic exposure and dissection of the Glisson's sheath to gain access to the hepatic artery and portal vein for reconstruction. METHODS: Following skeletonization of the hepatoduodenal ligament, the proximal portions of invaded vessels are exposed. If extra-hepatic attempts to access the distal portions of the invaded vessels fail, TGA can be used. The distal portion of the invaded right or right posterior Glisson's sheath is exposed following liver transection. The anterior portion of the wall of bile duct is cut and transected circumferentially including the fibrous plate tissue. The non-invaded portal vein and hepatic artery are isolated and dissected towards the hepatic hilum until the invaded distal portion of the vessels, and vascular reconstructions are performed. RESULTS: TGA was performed in 9 patients; 5 patients underwent left hemihepatectomy and 4 underwent left tri-sectionectomy. Eight patients needed vascular reconstruction. Clavien-Dindo classification (CDC) grades IIIa and IIIb were recorded in 6 and 1 patients, respectively. No patients had CDC grades IV and V disease. Pathologically, all cases were pT4; 3 cases were R0, 5 were R1 with microscopic positive margin, and 2 were R1 with microscopic metastasis. The overall median survival time was 25.0 months. CONCLUSIONS: TGA is feasible with acceptable prognosis and expands the surgical opportunities.

Salvage Hepatectomy for Recurrent Hepatocellular Carcinoma after Radiofrequency Ablation and/or Transcatheter Arterial Chemoembolization: A Propensity Score-Matched Analysis.

AIM: We aimed to evaluate the short- and long-term surgical outcomes of salvage hepatectomy for recurrent hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) and/or transcatheter arterial chemoembolization (TACE). METHODS: We reviewed the surgical outcomes of 90 recurrent HCC patients after RFA and/or TACE (salvage group) and 490 HCC patients without preoperative treatment (primary group). We performed 1:1 propensity score matching (PSM) between the 2 groups and matched 87 patients in each group. RESULTS: Before PSM, the salvage group was pathologically more advanced than the primary group. After PSM, there were no significant differences in the clinicopathological features between the groups. The outcomes of propensity score-matched groups were compared and there was no statistically significant difference between the 2 groups regarding perioperative outcomes and survival. Univariate and multivariate analyses of propensity score-matched HCC patients revealed that stage, tumor size, differentiation, and portal vein invasion were independent prognostic factors for survival. Preoperative RFA and/or TACE was not a prognostic factor in a propensity score-matched cohort. CONCLUSIONS: The short- and long-term surgical outcomes of the primary and salvage groups were similar under the matched clinicopathological background. Salvage hepatectomy might be an acceptable treatment for recurrent HCC patients after RFA and/or TACE.

[A Case of Locally Advanced Intrahepatic Cholangiocarcinoma Successfully Treated by Conversion Surgery after Hepatic Arterial Infusion Chemotherapy and Radiation Therapy].

The patient was a 63-year-old man. Computed tomography(CT)showed a 99mm in diameter low-density mass in hepatic segments 4 and 8 as the main locus. This tumor was diagnosed as intrahepatic cholangiocarcinoma and was suspected to invade to left and right Gleason's sheath, and radical cure was judged impossible. After hepatic arterial chemotherapy and radiotherapy were performed, tumor shrinkage was confirmed, and tumor markers also became negative. So he was referred to our hospital for surgical indication. CT revealed that the tumor did not invade to the left Gleason's sheath. After percutaneous transhepatic portal embolization, hepatic right trisectionectomy was performed. He was administered gemcitabine as an adjuvant chemotherapy for 1 year. One year 5 months after surgery, the patient is alive without relapse. Preoperative hepatic arterial chemotherapy and radiotherapy could be an effective treatment for unresectable locally advanced intrahepatic cholangiocarcinoma.

Huge hepatocellular carcinoma greater than 10 cm in diameter worsens prognosis by causing distant recurrence after curative resection.

BACKGROUND AND OBJECTIVES: This study aimed to evaluate the impact of huge (≥10 cm) hepatocellular carcinoma (HCC) to the recurrence pattern and the prognosis after hepatectomy. METHODS: 574 patients who underwent hepatectomy by 17 surgeons (Open 536 and Laparoscopic 38) for HCC without major vascular invasion from 1990 to 2013 at single institute were retrospectively analyzed. RESULTS: Huge tumor, age, HCV, multiple tumors and microscopic portal invasion are independent risk factors for overall survival (OS), and huge tumor, ICGR15 ≥16%, multiple tumors, moderate/poor histology, microscopic portal invasion and a positive pathological margin are risk factors for relapse-free survival (RFS). The 5-year OS and RFS of patients with huge HCC (n = 53) (42.9 and 14.2%) were significantly worse than those of patients with HCC <10 cm (n = 521) (71.3 and 33.1%). Huge tumor is an independent risk factor for initial extra-hepatic recurrence (Hazard ratio 7.86, P < 0.0001). The 5-year OS of patients with initial extra-hepatic recurrence (n = 55) was significantly worse than patients with intra-hepatic recurrence (n = 338) (16.8 vs. 50.5%). CONCLUSIONS: Huge HCC (≥10 cm) is an independent risk factor due to a high risk for initial extra-hepatic recurrence. Future systemic adjuvant therapy is needed for these patients. J. Surg. Oncol. 2017;115:324-329. © 2016 Wiley Periodicals, Inc.