Adult hepatocytes direct liver organogenesis through non-parenchymal cell recruitment in the kidney.

BACKGROUND & AIMS: Since the first account of the myth of Prometheus, the amazing regenerative capacity of the liver has fascinated researchers because of its enormous medical potential. Liver regeneration is promoted by multiple types of liver cells, including hepatocytes and liver non-parenchymal cells (NPCs), through complex intercellular signaling. However, the mechanism of liver organogenesis, especially the role of adult hepatocytes at ectopic sites, remains unknown. In this study, we demonstrate that hepatocytes alone spurred liver organogenesis to form an organ-sized complex 3D liver that exhibited native liver architecture and functions in the kidneys of mice. METHODS: Isolated hepatocytes were transplanted under the kidney capsule of monocrotaline (MCT) and partial hepatectomy (PHx)-treated mice. To determine the origin of NPCs in neo-livers, hepatocytes were transplanted into MCT/PHx-treated green fluorescent protein transgenic mice or wild-type mice transplanted with bone marrow cells isolated from green fluorescent protein-mice. RESULTS: Hepatocytes engrafted at the subrenal space of mice underwent continuous growth in response to a chronic hepatic injury in the native liver. More than 1.5 years later, whole organ-sized liver tissues with greater mass than those of the injured native liver had formed. Most remarkably, we revealed that at least three types of NPCs with similar phenotypic features to the liver NPCs were recruited from the host tissues including bone marrow. The neo-livers in the kidney exhibited liver-specific functions and architectures, including sinusoidal vascular systems, zonal heterogeneity, and emergence of bile duct cells. Furthermore, the neo-livers successfully rescued the mice with lethal liver injury. CONCLUSION: Our data clearly show that adult hepatocytes play a leading role as organizer cells in liver organogenesis at ectopic sites via NPC recruitment. LAY SUMMARY: The role of adult hepatocytes at ectopic locations has not been clarified. In this study, we demonstrated that engrafted hepatocytes in the kidney proliferated, recruited non-parenchymal cells from host tissues including bone marrow, and finally created an organ-sized, complex liver system that exhibited liver-specific architectures and functions. Our results revealed previously undescribed functions of hepatocytes to direct liver organogenesis through non-parenchymal cell recruitment and organize multiple cell types into a complex 3D liver at ectopic sites. Transcript profiling: Microarray data are deposited in GEO (GEO accession: GSE99141).

Risk Factors for Postoperative Ascites in Patients Undergoing Liver Resection for Hepatocellular Carcinoma.

BACKGROUND: Postoperative ascites is a common complication after liver resection. This study aimed to identify the risk factors for ascites in patients after liver resection and the relationship between postoperative ascites and other complications. METHODS: We retrospectively analyzed data that were obtained from 266 patients who underwent liver resection for treating hepatocellular carcinoma between 2008 and 2015. Postoperative ascites was defined as a daily ascitic fluid drainage exceeding 500 mL on postoperative day 3 or later. The participants were categorized and analyzed with respect to the presence or absence of postoperative ascites. RESULTS: Overall, 17 (6.4%) patients developed postoperative ascites. A multivariate analysis identified that three significant factors-serum albumin, platelet count, and operation duration-were associated with the development of postoperative ascites. Sixteen (94.1%) of the 17 patients with postoperative ascites experienced other associated complications. The patients with ascites had more pleural effusion (70.6 vs. 17.7%, P < 0.001) than the patients without ascites. Postoperative morbidity, except for pleural effusion, was similar between the groups. The postoperative hospital stay duration was significantly longer in patients with ascites than in those without ascites. CONCLUSIONS: Postoperative ascites frequently occurred in patients with decreased liver functional reserve. Moreover, the presence of ascites was associated with significantly increased pleural effusion rates, and postoperative hospital stay duration was significantly prolonged.

The Administration of Celecoxib as an Analgesic after Liver Resection Is Safe.

BACKGROUND: There are a few studies that have evaluated postoperative analgesia. The aim of this study was to evaluate the safety of administering celecoxib to manage postoperative pain after liver surgery. METHODS: The cases of patients who underwent liver resection at Nara Medical University from April 2008 to December 2015 were retrospectively analyzed. From January 2013 to December 2015, celecoxib was routinely administered (600 mg/day on postoperative day (POD) 2 and 400 mg/day from POD 3-7), whereas celecoxib was not administered from April 2008 to December 2012. The patients' baseline characteristics, the operative procedures, and postoperative complications were analyzed. RESULTS: In total, 207 patients were administered celecoxib (celecoxib group), whereas 246 were not (non-celecoxib group). The preoperative serum total bilirubin and creatinine levels and indocyanine green retention rate at 15 min values of the 2 groups were similar. Similar incidences of overall and major complications (Clavien-Dindo classification ≥grade IIIa) were seen in both groups (33.8 vs. 36.2%, p = 0.601 and 12.1 vs. 12.6%, p = 0.866, respectively). No significant differences in the incidences of gastrointestinal bleeding, acute renal failure, or portal vein thrombosis were observed between the groups. CONCLUSIONS: The use of celecoxib for postoperative analgesia in the early period after liver resection is safe.

Use of fondaparinux for thromboprophylaxis in an unfractionated heparin-intolerant pregnant woman with thrombotic predisposition.

A 34-year-old primigravida who had undergone thrombectomy for deep venous thrombosis (DVT) in her leg and exhibited low protein S activity, indicating predisposition to thrombosis, developed DVT of the leg. No pulmonary embolism was detected. After anticoagulant therapy with unfractionated heparin was discontinued because of liver dysfunction, danaparoid treatment was administered in hospital. The patient had a normal delivery after 39 weeks' gestation with no recurrence of thrombosis. During her second pregnancy four years later, she gave herself fondaparinux injections. She delivered normally after 38 weeks' gestation without experiencing DVT. Fondaparinux may be a useful anticoagulant for heparin-intolerant pregnant women.

Randomized Controlled Trial of Pancreaticojejunostomy versus Stapler Closure of the Pancreatic Stump During Distal Pancreatectomy to Reduce Pancreatic Fistula.

OBJECTIVES: The aim of this study was to evaluate in a multicenter randomized controlled trial (RCT) whether pancreaticojejunostomy (PJ) of pancreatic stump decreases the incidence of pancreatic fistula after distal pancreatectomy (DP) compared with stapler closure. BACKGROUND: Several studies reported that PJ of pancreatic stump reduces the incidence of pancreatic fistula after DP. However, no RCT has confirmed the efficacy of PJ of pancreatic stump. METHODS: One hundred thirty-six patients scheduled for DP were enrolled in this study between June 2011 and March 2014 at 6 high-volume surgical centers in Japan. Enrolled patients were randomized to either stapler closure or PJ. The primary endpoint was the incidence of pancreatic fistula based on the International Study Group on Pancreatic Fistula criteria. This RCT was registered with ClinicalTrials.gov (NCT01384617). RESULTS: Sixty-one patients randomized to stapler and 62 patients randomized to PJ were analyzed by intention-to-treat. Pancreatic fistula occurred in 23 patients (37.7%) in the stapler closure group and 24 (38.7%) in the PJ group (P = 0.332) in intention-to-treat analysis. The incidence of clinically relevant pancreatic fistula (grade B or C) was 16.4% for stapler closure and 9.7% for PJ (P = 0.201). Mortality was zero in both groups. In a subgroup analysis for thickness of pancreas greater than 12 mm, the incidence of clinically relevant pancreatic fistula occurred in 22.2% of the patients in the stapler closure group and in 6.2% of the PJ group (P = 0.080). CONCLUSIONS: PJ of the pancreatic stump during DP does not reduce pancreatic fistula compared with stapler closure.

Preoperative Cardiac Risk Assessment and Surgical Outcomes of Patients with Gastric Cancer.

PURPOSE: To evaluate the incidence of major adverse cardiac events (MACE) and long-term surgical outcomes after gastrectomy for gastric cancer using the revised cardiac risk index (RCRI), which is based on preoperative insulin use, serum creatinine >2.0 mg/dL, and history of ischemic or congestive heart failure or cerebrovascular disease. METHODS: We allocated 1000 patients who underwent elective gastrectomy to three groups with ≥3 (group A, n = 32), 2 (group B, n = 142), or 1 (group C, n = 826) of these factors and compared surgical complications and prognoses. RESULTS: Groups A and B had older patients than group C. Group B had more male patients than groups A and C. Tumor staging and gastrectomy type were similar among all groups. D1 lymph node dissection was more frequent in group A than in groups B or C. The incidence of MACE in groups A, B, and C was 25.0, 9.9, and 1.1 %, respectively. RCRI was associated with MACE. Furthermore, the incidence of pneumonia and in-hospital mortality was associated with RCRI risk factors. However, the incidence of anastomotic leakage, intra-abdominal abscess, wound infection, and pancreas-related infection were similar among the groups. The 5-year overall survival rates of the three groups were 44.3, 65.2, and 80.8 %, which were significantly different. CONCLUSIONS: Patients with RCRI factors have an increased risk of MACE, pneumonia, and higher mortality after gastrectomy; thus, careful patient selection and meticulous perioperative care are crucial for successful gastrectomy.

Visualization of Lymph/Blood Flow in Laparoscopic Colorectal Cancer Surgery by ICG Fluorescence Imaging (Lap-IGFI).

PURPOSE: In laparoscopic colorectal cancer (Lap-CRC) surgery, determination of a suitable mesentery division line and the appropriate degree of lymphadenectomy by tracing the blood supply is critical. We performed visualization of the lymph and blood flow by laparoscopic indocyanine green (ICG) fluorescence imaging (Lap-IGFI). METHODS: ICG is injected into the submucosa near the tumor via colonoscopy, and the lymph flow is observed. Intestinal blood flow is evaluated by administering ICG intravenously. RESULTS: For lymph flow, visualization of the main lymph node basin helped to determine the surgical division line for cases in which the blood flow was not completely visualized. Lap-IGFI changed the surgical plan of the lymphadenectomy in 23.5 %. In our experience, the metastatic rate of ICG-positive nodes was 10.0 %, and the metastatic rate of ICG-negative nodes was 5.3 %. Furthermore, there were no metastatic nodes that were ICG negative more than 5 cm from the tumor. For blood flow, the blood flow distribution of the intestinal wall from the last branch of the vasa recta of the anastomotic site was clearly visualized and proved useful in choosing the extent of intestinal resection. Lap-IGFI changed the surgical plan of the extensive intestinal resection in 16.7 %. CONCLUSIONS: Lap-IGFI can noninvasively provide detailed lymph and blood flow information and is a useful device to aid in the accurate identification of individual patients' lymph drainage. This helps dictate adequate lymphadenectomy and the extent of intestinal resection in Lap-CRC surgery.

Keratin 19 as a key molecule in progression of human hepatocellular carcinomas through invasion and angiogenesis.

BACKGROUND: Keratin (K) 19-positive hepatocellular carcinoma (HCC) is well known to have a higher malignant potential than K19-negative HCC: However, the molecular mechanisms involved in K19-mediated progression of HCC remain unclear. We attempted to clarify whether K19 directly affects cell survival and invasiveness in association with cellular senescence or epithelial-mesenchymal transition (EMT) in K19-positive HCC. METHODS: K19 expression was analysed in 136 HCC surgical specimens. The relationship of K19 with clinicopathological factors and survival was analysed. Further, the effect of K19 on cell proliferation, invasion, and angiogenesis was examined by silencing K19 in the human HCC cell lines, HepG2, HuH-7, and PLC/PRF/5. Finally, we investigated HCC invasion, proliferation, and angiogenesis using K19-positive HCC specimens. RESULTS: Analysis of HCC surgical specimens revealed that K19-positive HCC exhibited higher invasiveness, metastatic potential, and poorer prognosis. In vitro experiments using the human HCC cell lines revealed that K19 silencing suppressed cell growth by inducting apoptosis or upregulating p16 and p27, resulting in cellular senescence. In addition, transfection with K19 siRNA upregulated E-cadherin gene expression, significantly inhibited the invasive capacity of the cells, downregulated angiogenesis-related molecules such as vasohibin-1 (VASH1) and fibroblast growth factor 1 (FGFR1), and upregulated vasohibin-2 (VASH2). K19-positive HCC specimens exhibited a high MIB-1 labelling index, decreased E-cadherin expression, and high microvessel density around cancer foci. CONCLUSION: K19 directly promotes cancer cell survival, invasion, and angiogenesis, resulting in HCC progression and poor clinical outcome. K19 may therefore be a novel drug target for the treatment of K19-positive HCC.

Increased tumour ADC value during chemotherapy predicts improved survival in unresectable pancreatic cancer.

OBJECTIVES: To investigate whether changes to the apparent diffusion coefficient (ADC) of primary tumour in the early period after starting chemotherapy can predict progression-free survival (PFS) or overall survival (OS) in patients with unresectable pancreatic adenocarcinoma. METHODS: Subjects comprised 43 patients with histologically confirmed unresectable pancreatic cancer treated with first-line chemotherapy. Minimum ADC values in primary tumour were measured using the selected area ADC (sADC), which excluded cystic and necrotic areas and vessels, and the whole tumour ADC (wADC), which included whole tumour components. Relative changes in ADC were calculated from baseline to 4 weeks after initiation of chemotherapy. Relationships between ADC and both PFS and OS were modelled by Cox proportional hazards regression. RESULTS: Median PFS and OS were 6.1 and 11.0 months, respectively. In multivariate analysis, sADC change was the strongest predictor of PFS (hazard ratio (HR), 4.5; 95 % confidence interval (CI), 1.7-11.9; p = 0.002). Multivariate Cox regression analysis for OS revealed sADC change and CRP as independent predictive markers, with sADC change as the strongest predictive biomarker (HR, 6.7; 95 % CI, 2.7-16.6; p = 0.001). CONCLUSION: Relative changes in sADC could provide a useful imaging biomarker to predict PFS and OS with chemotherapy for unresectable pancreatic adenocarcinoma. KEY POINTS: • Relative change in ADC value can predict survival in unresectable pancreatic cancer. • ADC change could determine a chemosensitivity of pancreatic cancer. • ADC values should be measured by excluding cystic, necrotic areas and vessels.

The prognosis of liver resection for patients with four or more colorectal liver metastases has not improved in the era of modern chemotherapy.

BACKGROUND AND OBJECTIVES: The impact of perioperative chemotherapy on patients with multiple colorectal liver metastases (CRLM) remains unclear. We attempted to examine whether the introduction of modern chemotherapies has improved the prognosis of patients that undergo liver resection for ≥4 CRLM. METHODS: Between January 1990 and December 2013, 194 patients underwent liver resection for CRLM at our institution. The outcomes of the patients with ≥4 and 1-3 CRLM were compared before and after 2005, when modern chemotherapies were introduced to Japan. RESULTS: There were 50 and 144 patients with ≥4 (Group 1) and 1-3 (Group 2) CRLM, respectively. The overall survival (OS) rate of Group 1 was significantly worse than that of Group 2 (P = 0.0007). The OS rate of Group 2 was significantly better after 2005 than before 2004 (P = 0.039), while no such differences were observed in Group 1. Multivariate analysis identified three prognostic factors in Group 1: a serum carcinoembryonic antigen level of ≥20 ng/ml (P = 0.018), a serum cancer antigen 19-9 level of ≥100 U/ml (P = 0.018), and a primary colorectal cancer N factor of ≥N2 (P = 0.023). CONCLUSIONS: The prognosis of patients with ≥4 CRLM that undergo liver resection has not improved despite the development of modern chemotherapies. J. Surg. Oncol. 2016;114:959-965. © 2016 Wiley Periodicals, Inc.

Impact of being underweight on the long-term outcomes of patients with gastric cancer.

BACKGROUND: The aim of this study was to investigate the impact of being underweight on the long-term outcomes of gastric cancer patients. METHODS: This study reviewed the medical records of 638 patients with gastric cancer who underwent gastrectomy between January 2003 and December 2011. The patients were divided into three groups according to the WHO classification: underweight (BMI <18.5 kg/m(2)), normal weight (BMI ≥18.5 and <25 kg/m(2)), and overweight (BMI ≥25 kg/m(2)). A multivariate analysis was performed to identify prognostic factors. RESULTS: The mean BMI immediately before surgery was 22.5 kg/m(2) (standard deviation, 3.3 kg/m(2)). According to the BMI subgroup, 73 patients (11.4 %) were underweight, 431 patients (67.6 %) were of normal weight, and 134 patients (21 %) were overweight. The 5-year overall survival (OS) rate was 66.6 % in the underweight patients, 81.3 % in the normal weight patients, and 79.9 % in the overweight patients (P = 0.001). The OS rate was significantly lower in the underweight patients than in the normal weight and overweight patients among those with stage I disease, and it was also lower than in the normal weight patients among those with stage II and III disease. In the multivariate analysis, being underweight was found to be an independent predictor of OS, but it was not an independent predictor among patients with stage II and III disease. CONCLUSIONS: Being underweight is a simple and reliable predictor of a worse long-term outcome among gastric cancer patients. Being underweight is considered to be associated with a higher risk of non-cancer death.

The anatomical location of the pancreas is associated with the incidence of pancreatic fistula after laparoscopic gastrectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) is one of the major complications after laparoscopic gastrectomy (LG). We investigated the impact of the anatomical location of the pancreas, especially in relation to the suprapancreatic lymph nodes, on the incidence of POPF after LG. METHODS: We retrospectively reviewed the preoperative computed tomography (CT) images of 246 patients who underwent LG with the suprapancreatic lymph node dissection between November 2008 and November 2015. The length between the levels of the pancreatic body surface and the root of the common hepatic artery (LPC) was measured on a CT image with an axial view. A receiver operating characteristics (ROC) curve analysis was performed to determine the cutoff LPC value. A multivariate analysis was performed to determine the predictive factors for POPF. RESULTS: POPF occurred in 11 patients (4.5 %). The median LPC was significantly longer in the patients with POPF than in those without (26 mm vs. 21 mm, p = 0.026). The ROC curve analysis revealed that the optimal cutoff LPC value for predicting POPF was 25 mm. The POPF rate was significantly higher in the long LPC group than in the short LPC group (10 vs. 1.3 %, p = 0.002). A multivariate analysis demonstrated that a long LPC (p = 0.018) and dissection of the lymph nodes along the distal splenic artery (p = 0.042) were independent predictors of POPF. The amylase level in the drainage fluid on postoperative day 1 was significantly higher in the long LPC group than in the short LPC group. CONCLUSIONS: The LPC is a simple and reliable predictor of POPF after LG. Surgeons should take the anatomical location of the pancreas into consideration when performing LG with suprapancreatic lymph node dissection.

Intraluminal lavage to remove exfoliated tumor cells after colorectal endoscopic submucosal dissection.

BACKGROUND: Endoscopic submucosal dissection (ESD) involves dissection of tumors and manipulation of them in an exposed condition for prolonged periods. A large number of tumor cells are exfoliated into the intestinal lumen after colorectal ESD. The aim of this study was to determine whether lavage volume has an influence on tumor cell clearance after colorectal ESD. METHODS: Twenty patients who underwent colorectal ESD at our hospital between July 2013 and December 2014 were studied. Cytological examination of intraluminal lavage samples associated incremental increases in lavage volume was collected. This prospective study was approved by the ethics committee of our hospital. RESULTS: No patients had exfoliated tumor cells in their samples before ESD. Four patients (20 %) had exfoliated tumor cells in their samples after lavage with 500 ml, while one patient (5 %) had exfoliated tumor cells after lavage with 1000 or 1500 ml. CONCLUSION: Tumor cells are exfoliated into the intestinal lumen by tumor manipulation during colorectal ESD. There seems to be a risk for implantation after ESD, as well as rectal surgery. Sufficient intraluminal lavage of more than 1000 ml may be desirable to remove exfoliated tumor cells after colorectal ESD.

Outcomes of Laparoscopic Liver Resection for Patients with Large Colorectal Liver Metastases: A Case-Matched Analysis.

BACKGROUND: Despite the expansion of laparoscopic approach in the treatment of liver tumors, limited data have been reported regarding large colorectal liver metastases (CRLMs). This study aimed at assessing the short- and long-term outcomes after laparoscopic liver resection (LLR) for large (≥5 cm) CRLMs. METHODS: This was a case-matched study (1:2) comparing patients with large (group L; ≥5 cm) and small (group S; <5 cm) CRLMs using demographic, tumor, and surgical characteristics as matching variables. Postoperative outcomes and survival data were compared in the 2 groups. RESULTS: Forty patients who underwent LLR for large CRLMs were matched with 80 patients with tumors <5 cm. Major hepatectomy was performed with 75.0 % of patients in Group L and 66.3 % in group S (p = 0.403). Operative time was 300 min in group L and 240 min in group S (p = 0.059). The postoperative mortality and overall morbidity rates were comparable in the 2 groups (p = 1.000 and 0.170, respectively). Postoperative major complication (Dindo-Clavien ≥3) was similar between the two groups (p = 0.072). R0 resection was achieved in 92.5 % in the group L and in 95.0 % in the group S (p = 1.000). The 5-year overall survival and recurrence-free survival were better for group S than for group L (47.3 vs. 35.4 %, p = 0.044 and 27.3 vs. 14.9 %, p = 0.042, respectively). Multivariate analysis identified positive surgical margins and synchronous presentation as prognostic factors. CONCLUSION: Since LLR was performed safely with favorable oncological adequacy in selected patients with large CRLMs, tumor size should not modify the surgical approach.

Impact of Mechanical Bowel Preparation on Postoperative Outcomes after Liver Resection for Patients with Hepatocellular Carcinoma: A Single-Center Retrospective Cohort Study.

BACKGROUND: Despite the routine use of mechanical bowel preparation (MBP), the real impact of MBP for liver resection remains unclear. The aim of this study was to evaluate the postoperative outcomes of MBP after liver resection for hepatocellular carcinoma (HCC). METHODS: This was a retrospective cohort study of all patients undergoing liver resection for patients with HCC between from April 2008 to March 2015. MBP was defined as a preoperative medication of polyethylene glycol lavage. We compared perioperative outcomes in patients who did or did not receive MBP before liver resection. Open and laparoscopic hepatectomy were analyzed separately. RESULTS: A total of 227 patients underwent potentially curative liver resection for HCC during the study period. One hundred twenty-eight patients received MBP while 99 did not. In the open hepatectomy group, overall and major (Clavien-Dindo ≥3) complications were equivalent between the groups (31.9 vs. 25.8%, p = 0.840; 12.1 vs. 8.7%, p = 0.475). There were no meaningful differences in the incidence of liver failure (MBP: 22.4%, non-MBP: 13.0%, p = 0.116). Surgical-site infections occurred in 20 (17.2%) vs. 10 (14.5%) with no significant difference (p = 0.624). Similar results were obtained from the laparoscopic hepatectomy group. CONCLUSION: The use of MBP does not appear to impact the short outcomes after liver resection for patients with HCC. MBP might be omitted in liver surgery.

[Long-Term Survival of a Patient with Sigmoid Colon Cancer with Multiple Visceral Metastases].

A 66-year-old woman underwent total pelvic exenteration for a pelvic tumor. The pathological diagnosis was sigmoid colon cancer T4b(in the small intestine, uterus, and vagina), N0, M0, Stage II . The patient was treated with XELOX for 6 months as adjuvant chemotherapy and was then treated with IRIS for another 6 months. Brain metastasis developed in the left occipital lobe after 12 months, and she underwent craniotomy and enucleation of the tumor. Liver metastasis and peritoneal dissemination metastasis developed 16 months after her initial diagnosis. The patient underwent re-craniotomy and radiotherapy for recurrence of the brain metastasis 18 months after diagnosis and started taking TAS-102 3 months later. She began treatment with CPT-11 plus panitumumab 24 months after diagnosis, and the dose was increased 9 months later(ie, 35 months after the initial diagnosis). The patient remains alive 42 months after surgery.

[A Resected Case of Cecal Cancer with Simultaneous Liver, Spleen, and Ovarian Metastasis and Peritoneal Dissemination].

We herein report the case of a patient with a cecal cancer with simultaneous liver, spleen, and ovarian metastases as well as peritoneal dissemination who achieved a long-term survival. The patient was a 67-year-old female. Ileocecal resection with partial hepatectomy, splenectomy, simple total hysterectomy, bilateral salpingo-oophorectomy, and resection of the peritoneal dissemination were performed. The final diagnosis was Stage IV (T4a, N1, M1b[H1, P3, OTH]). Adjuvant chemotherapy was administered, but abdominal computed tomography(CT)revealed a metachronous liver metastasis 41 months later. We performed partial hepatectomy, and the patient continued adjuvant chemotherapy. The patient is currently alive and disease-free 30 months after the last operation, 72 months after the initial surgery.

[Long-Term Survival in a Case of Sigmoid Colon Cancer with Multiple Liver Metastases Treated with Repeated Hepatectomies].

A 75-year-old man was diagnosed with sigmoid colon cancer with multiple liver metastases at our hospital in May 2010. He underwent mFOLFOX6 and panitumumab chemotherapy for 6 months. He then underwent sigmoidectomy, lymphadenectomy D3, partial resection of 2 parts of S6, and cholecystectomy in January 2011. However, he underwent partial resection of the liver an additional 4 times in the 5 years followingthe primary operation. Despite multiple liver metastases, he is alive 5 years after the primary operation, havingsurvived 5 hepatectomies for multiple resectable liver metastases.

[A Case of Advanced Hepatocellular Carcinoma, Its Disease Progression Could Be Controlled by Multimodal Treatment].

The patient was a 73-year-old man, diagnosed with advanced huge hepatocellular carcinoma with a tumor thrombus extending into the inferior vena cava and extrahepatic metastases. Radiation therapy(50 Gy)was applied for the bone metastases, primary tumor, and tumor thrombus, and the patient received a cisplatin transcatheter arterial infusion(100mg/ body, 5 courses). Sorafenib was administered orally once the local lesion was under control. The tumor showed a partial response according to the RECIST criteria, but the tumor thrombus in the inferior vena cava almost disappeared. The presence of a tumor thrombus in the inferior vena cava must be regarded as an oncologic emergency. Acisplatin transcatheter arterial infusion and radiation therapy may be treatment options for unresectable cases.

[Huge Hepatocellular Carcinoma with Portal Vein and Inferior Vena Cava Thrombi Treated with Curative Liver Resection and Perioperative Hepatic Arterial Infusion Chemotherapy - A Case Report].

The prognosis of hepatocellular carcinoma(HCC)with main portal vein(MPV)and/or the inferior vena cava(IVC)tumor thrombi is dismal. The management of HCC with severe tumor thrombus is complicated. In this study, we report a case of HCC with tumor thrombi in the MPV and IVC that was successfullytreated via liver resection and perioperative hepatic arterial infusion chemotherapy(HAI). A 68-year-old man was referred to our institution to treat huge HCC lesion in the right lobe of the liver. Abdominal computed tomography(CT)revealed a tumor(12 cm in diameter)in the right hepatic lobe and tumor thrombi in the MPV and IVC. The patient was initiallytreated with HAI(cisplatin 100mg/body). After 3 courses of HAI, the tumor was dramaticallyreduced in size, and the thrombus in the IVC had disappeared; however, the thrombus in the MPV remained. Therefore, we performed right hepatectomy, wedge resection of the IVC, combined resection of the MPV, and portal vein reconstruction. The histopathological findings of the resected specimen revealed that viable cancer cells were observed onlyin an 8×8mm lesion. Subsequently, HAI was performed as adjuvant therapy for 3 courses. The patient died of other causes 2 years 3 months after surgery. There was no sign of recurrence at the time of death. This case suggested that perioperative HAI and liver resection mayrepresent an effective treatment strategyfor HCC with severe tumor thrombus.