Phosphorylated mTOR expression as a predictor of survival after liver resection for colorectal liver metastases.

BACKGROUND: Phosphorylated mammalian target of rapamycin (p-mTOR) plays a crucial role in the process of cancer progression. Common gene mutations of colorectal cancer lead to the activation of the PI3k/Akt/mTOR pathway. In this study, we determined whether p-mTOR expression in colorectal liver metastases is a predictive marker of prognosis following liver resection. METHODS: Eighty-one patients with colorectal liver metastases who had undergone curative resection were evaluated using immunohistochemistry of p-mTOR. Data regarding clinicopathological features and patient survival were analyzed. RESULTS: The p-mTOR expression in colorectal liver metastases was detected in 55 (67.9%) patients. Patients whose metastases had high p-mTOR expression showed a significantly lower overall survival rate after resection as compared to patients with low p-mTOR expression (p = 0.016), while there was no significant difference in the disease-free survival between the two groups. Repeat resection for recurrence was performed more frequently in patients with p-mTOR positive than others (p = 0.024). Multivariate analysis showed that p-mTOR expression was an independent prognostic factor of overall survival after liver resection (p = 0.019). CONCLUSIONS: mTOR was frequently activated in colorectal liver metastases, and the p-mTOR expression was a biological marker for predicting the overall survival of patients with colorectal liver metastases following liver resection.

[A Case Report of Cancer Chemotherapy for Disseminated Carcinomatosis of the Bone Marrow Associated with Gastric Cancer Accompanied by Disseminated Intravascular Coagulation].

A 72-year-old woman was admitted to our hospital because of symptoms of bleeding diathesis such as hematuria and purpura. A blood test revealed disseminated intravascular coagulation(DIC). Upper gastrointestinal endoscopy showed advanced gastric cancer. Bone marrow aspiration cytology demonstrated diffuse hyperplasia of large atypical cells, and metastasis of the epithelial tumor was suspected on immunohistochemical examination. She was diagnosed with disseminated carcinomatosis of the bone marrow associated with gastric cancer accompanied by DIC. She was treated with weekly infusion of methotrexate 100 mg/m2 plus 5-fluorouracil 600 mg/m2 for 4 courses; and she completely recovered from DIC. She received oral tegafur/gimeracil/oteracil as an outpatient. However, DIC recurred 126 days after the initial chemotherapy, and 5-fluorouracil plus cisplatin was administered subsequently. After 1 course, she died 166 days after the initial chemotherapy. Although the prognosis of patients with disseminated carcinomatosis of the bone marrow associated with gastric cancer accompanied by DIC is extremely poor, this case shows that secession of DIC and prognostic improvement by chemotherapy could occur. Chemotherapy could be considered a potentially effective treatment in this case.

Splenic enlargement induced by preoperative chemotherapy is a useful indicator for predicting liver regeneration after resection for colorectal liver metastases.

BACKGROUND: Conversion chemotherapy may downsize unresectable colorectal liver metastases (CRLMs), but may cause liver injury and splenic enlargement. The effect of preoperative chemotherapy on liver regeneration after liver resection remains undetermined. The aim of this study was to examine whether splenic enlargement induced by preoperative chemotherapy is an indicator to identify high-risk patients for impaired liver regeneration and liver dysfunction after resection. METHODS: We retrospectively reviewed 118 Japanese patients with CRLMs. Fifty-one patients had conversion chemotherapy. The other 67 patients underwent up-front liver resection. We clarified effects of conversion chemotherapy on splenic volume, liver function, and postoperative liver regeneration. Perioperative outcome was also analyzed. RESULTS: A ratio of the splenic volume before and after chemotherapy (SP index) in the oxaliplatin-based chemotherapy group was significantly greater than other chemotherapy groups after 9 or more chemotherapy cycles. Patients whose SP index was 1.2 or more had significantly higher indocyanine green retention rate at 15 min (ICG-R15) than patients without chemotherapy. Analyses of covariance showed liver regeneration rate after resection was decreased in patients whose SP index was 1.2 or more. The incidence of postoperative liver dysfunction in patients whose SP index was 1.2 or more was significantly greater than patients without chemotherapy. Multivariate analysis showed SP index was a significant predictive factor of impaired liver regeneration. CONCLUSIONS: Splenic enlargement induced by preoperative chemotherapy was a useful indicator for impaired liver regeneration after resection and a decision-making tool of treatment strategy for unresectable CRLMs.

Combined hepatic arterial resection in pancreatic resections for locally advanced pancreatic cancer.

PURPOSE: Arterial involvement in advanced pancreatic cancer generally defines local unresectability. This study was aimed to evaluate the clinical outcomes of combined common hepatic arterial resection with pancreaticoduodenectomy or total pancreatectomy in patients with locally advanced pancreatic cancer involving the hepatic artery. METHODS: Of 348 patients with pancreatic head cancers who underwent surgical resection between June 1999 and September 2015, 21 underwent combined common hepatic arterial resection with pancreaticoduodenectomy (17) or total pancreatectomy (4). Preoperative common hepatic arterial embolization was performed in 12 patients. Preoperative CT findings of hepatic arterial involvement, postoperative complications, survival rates, and prognostic factors for survival were analyzed. Twenty-one unresectable patients with locally advanced pancreatic cancer who underwent laparotomy in this study period were selected as the control group. RESULTS: Rates of pathological arterial invasion were significantly higher in patients with level III (>1800) CT findings (90%,9/10) than in patients with levels I and II (<1800) (27%, 3/11) (p < 0.01). No surgical deaths occurred. Survival after surgical resection in all 21 patients was 47.6%, 6.6%, and 6.6% at 1, 3, and 5 years, and median survival was 11 months. The preoperative serum CA19-9 level was a significant prognostic factor for overall survival, median survivals were 21.5 and 8.3 months in the low CA19-9 and high CA19-9 groups, respectively. No significant difference in survival between the high-CA19-9 group and the unresectable group was found. CONCLUSIONS: Combined common hepatic arterial resection in pancreaticoduodenectomy or total pancreatectomy might be feasible with an acceptable rate of surgical complications, and may have a beneficial effect on the prognosis only in patients with low preoperative serum CA19-9 levels.

Downsizing Chemotherapy for Initially Unresectable Locally Advanced Biliary Tract Cancer Patients Treated with Gemcitabine Plus Cisplatin Combination Therapy Followed by Radical Surgery.

BACKGOUND: We have treated patients with initially unresectable locally advanced biliary tract cancer (BTC) by administering gemcitabine and have found that surgical resection became feasible in some downsized patients. The aim of this study was to investigate the usefulness of downsizing combination chemotherapy using gemcitabine plus cisplatin to treat initially unresectable locally advanced BTC. METHODS: The subjects of the study were 150 consecutive patients who were treated for BTC between October 2011 and April 2014. Downsizing chemotherapy was carried out for 39 patients (26.0 %) whose lesions were unresectable because of locally advanced BTC. RESULTS: Reduction in tumor size with downsizing chemotherapy was seen in 18 patients, and surgical resection was performed in 10 of 39 patients (25.6 %). Median survival time in patients with surgical resection following downsizing chemotherapy and those with chemotherapy alone was 17.9 and 12.4 months, respectively (p = 0.0378). According to the historical comparison between gemcitabine and gemcitabine plus cisplatin chemotherapy, there is no significant difference in overall survival. However, there was a significant difference for the pathologic response rate (≥Grade III) to be higher in patients with gemcitabine plus cisplatin chemotherapy compared with gemcitabine monotherapy. CONCLUSIONS: Preoperative downsizing chemotherapy with gemcitabine plus cisplatin provides longer survival by the conversion to the surgical resection in patients with initially unresectable locally advanced BTC. It may have the potential for disease eradication as a new multidisciplinary approach for initially unresectable locally advanced BTC.

[A Case of Long-Term Survival in a Patient with Colorectal Liver Metastasis Treated with Multidisciplinary Therapy].

A-71-year-old man underwent right hemicolectomy combined with partial resection of the small intestine and duodenum for an ascending colon carcinoma in July 2009. He presented with a liver metastasis adjacent to the inferior vena cava in November 2009. He received 6 courses of FOLFOX4, but the therapeutic effect was SD, so he underwent an extended posterior sectionectomy combined with partial S8 resection, inferior vena cava resection, and cholecystectomy. He developed remnant liver recurrence in February 2011 and another partial S8 resection was performed. He presented with remnant liver recurrence in October 2011, and radiofrequency ablation and systemic chemotherapy were performed, but were not effective. In June 2013, we performed an extended S8 segmentectomy combined with median hepatic vein and diaphragm resection. He is alive 2 years after the third hepatectomy without any recurrence. Although non-anatomical resection is often performed in repeat liver resections for colorectal liver metastases, sometimes detection of recurrent lesions in the same segment indicates Glisson invasion; therefore, anatomic resection may prolong long-term survival.

[Hepatocellular Carcinoma with Vp3 Tumor Thrombosis Treated with Multidisciplinary Treatment--Report of Two Cases].

Hepatic resection of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) at the bifurcation of the portal has the potential to cure the disease. Herein, we report 2 cases of HCC with Vp3 treated with a multidisciplinary approach that might include preoperative transcatheter arterial chemoembolization (TACE) or postoperative hepatic arterial infusion chemotherapy (HAIC). Case 1: A 73-year-old man was diagnosed with HCC with Vp3 located in segment 1 during follow up that was treated by performing a left hepatectomy with removal of the tumor thrombus. After surgery, the patient underwent HAIC, and he was alive without disease recurrence 2 years and 2 months after surgery. Case 2: A 77-year-old man with cirrhotic nonalcoholic steatohepatitis underwent liver resection followed by TACE. However, recurrent HCC with Vp3 was detected in segments 2 and 5, so we performed a repeat liver resection. The patient was alive without disease recurrence 1 year and 8 months after surgery without having received postoperative adjuvant chemotherapy. In select patients diagnosed with HCC with PVTT (Vp3/4), long-term survival can be obtained with multidisciplinary treatment such as surgery and preoperative TACE or postoperative HAIC.

Surgical strategy for hilar cholangiocarcinoma of the left-side predominance: current role of left trisectionectomy.

OBJECTIVE: To evaluate recent surgical strategy for hilar cholangiocarcinoma (HC) of the left-side predominance. BACKGROUND: When employing left hemihepatectomy (LH) for HC, vasculobiliary anatomy of the right liver often makes it difficult to achieve a tumor-free margin of the right posterior sectional bile duct (RPSBD). Because left trisectionectomy (LTS) can produce a longer resection margin for the RPSBD, we have expanded the indications for LTS over the last 5 years. METHODS: Sixty-one consecutive patients underwent left-sided hepatectomy for HC, divided into 2 groups according to the operative periods: period 1 (2001-2007; n = 29) and period 2 (2008-2012; n = 32). Clinicopathological outcomes of the groups were compared. The difference in the length of the resectable RPSBD between LH and LTS was radiologically investigated using multidetector-row computed tomography. RESULTS: The proportion of LTS increased from 10.3% (3/29) in period 1 to 46.9% (15/32) in period 2. R0 resection rates were also improved in period 2. The most common margin positive site in period 1 was the stump of the proximal bile duct; high rates of positive RPSBD stump were noted after LH. The positive proximal ductal margin ratio decreased significantly in period 2. The difference in the length of resectable RPSBD between LH and LTS was 9.0 ± 1.3 mm. There was no mortality in period 2, even after LTS. CONCLUSIONS: LTS for HC of the left-side predominance improved R0 resection rates without affecting postoperative mortality. LTS should be aggressively performed in patients with appropriate hepatic function, even if tumors are possibly resectable by LH.

Protective effects of simultaneous splenectomy on small-for-size liver graft injury in rat liver transplantation.

Splenectomy is an effective technique in living donor liver transplantation (LDLT) with small-for-size (SFS) liver grafts for overcoming SFS liver graft injury. However, the protective mechanism of splenectomy is still unclear. The aim of this study was to investigate how splenectomy could attenuate SFS graft injury through the measurement of biochemical factors, particularly the expression of endothelin (ET)-1, which is a key molecule of microcirculatory disorders by mediating sinusoidal vasoconstriction. We performed rat orthotopic liver transplantation using SFS liver grafts with or without splenectomy. We investigated intragraft expression of ET-1 mRNA and hepatic protein levels of ET-1. In addition, portal pressure, hepatic injury and morphological changes, and survival rate were evaluated. In result, intragraft ET-1 mRNA expression after SFS liver transplantation was significantly downregulated by splenectomy, and hepatic expression of ET-1 in SFS grafts was rarely observed. Splenectomy inhibited the increase in portal pressure, ameliorated SFS liver graft injury and improved the graft survival rate after SFS liver transplantation. In conclusion, splenectomy improved the SFS liver injury and decreased the expression of ET-1 by attenuating portal hypertension on SFS liver transplantation. Downregulation of intragraft ET-1 expression plays important roles in the protective mechanism of splenectomy in SFS liver transplantation.

Left hepatic trisectionectomy for hepatolithiasis with occluded left and right anterior branches of the portal vein: report of a case.

A 64-year-old male was admitted to a local hospital with epigastric pain. Diagnostic imaging revealed hepatolithiasis in the atrophic left lobe. However, endoscopic intervention was impossible because of the presence of many large stones. He was referred to our hospital for surgical treatment. Enhanced multidetector-row computed tomography revealed that the right posterior portal vein (PV) was branched from the portal trunk as a first-order branch, and the bile duct of segment 3 ran caudally to the umbilical portion of the left PV. Furthermore, the umbilical portion of the left PV, which was located between the dilated bile ducts of segment 2 and segment 3, and also the right anterior PV, was occluded with thrombus. Based on these findings, he underwent left hepatic trisectionectomy. Although the indications for left hepatic trisectionectomy for hepatolithiasis are limited, it is therefore extremely important to determine the most appropriate surgical procedure based on the anatomy and findings of hepatic hilus in individual cases.

Surgical resection after downsizing chemotherapy for initially unresectable locally advanced biliary tract cancer: a retrospective single-center study.

BACKGROUND: Surgical resection is the only method for curative treatment of biliary tract cancer (BTC). Recently, an improved efficacy has been revealed in patients with initially unresectable locally advanced BTC to improve the prognosis by the advent of useful cancer chemotherapy. The aim of this study was to evaluate the effect of downsizing chemotherapy in patients with initially unresectable locally advanced BTC. METHODS: Initially unresectable locally advanced cases were defined as those in which therapeutic resection could not be achieved even by proactive surgical resection. Gemcitabine was administered intravenously once a week for 3 weeks followed by 1 week's respite. Patients whose disease responded to chemotherapy were reevaluated to determine whether their tumor was resectable. RESULTS: Chemotherapy with gemcitabine was provided to 22 patients with initially unresectable locally advanced BTC. Tumor was significantly downsized in nine patients, and surgical resection was performed in 8 (36.4%) of 22 patients. Surgical resection resulted in R0 resection in four patients and R1 resection in four patients. Patients who underwent surgical resection had a significantly longer survival compared with those unable to undergo surgery. CONCLUSIONS: Preoperative chemotherapy enables the downsizing of initially unresectable locally advanced BTC, with radical resection made possible in a certain proportion of patients. Downsizing chemotherapy should be proactively carried out as a multidisciplinary treatment strategy for patients with initially unresectable locally advanced BTC with the aim of expanding the surgical indication.

Kinetics and protective role of autophagy in a mouse cecal ligation and puncture-induced sepsis.

INTRODUCTION: It is not well understood whether the process of autophagy is accelerated or blocked in sepsis, and whether it is beneficial or harmful to the immune defense mechanism over a time course during sepsis. Our aim was to determine both the kinetics and the role of autophagy in sepsis. METHODS: We examined autophagosome and autolysosome formation in a cecal ligation and puncture (CLP) mouse model of sepsis (in C57BL/6N mice and GFP-LC3 transgenic mice), using western blotting, immunofluorescence, and electron microscopy. We also investigated the effect of chloroquine inhibition of autophagy on these processes. RESULTS: Autophagy, as demonstrated by increased LC3-II/LC3-I ratios, is induced in the liver, heart, and spleen over 24 h after CLP. In the liver, autophagosome formation peaks at 6 h and declines by 24 h. Immunofluorescent localization of GFP-LC3 dots (alone and with lysosome-associated membrane protein type 1 (LAMP1)), as well as electron microscopic examination, demonstrate that both autophagosomes and autolysosomes are increased after CLP, suggesting that intact autophagy mechanisms operate in the liver in this model. Furthermore, inhibition of autophagy process by chloroquine administration immediately after CLP resulted in elevated serum transaminase levels and a significant increase in mortality. CONCLUSIONS: All autophagy-related processes are properly activated in the liver in a mouse model of sepsis; autophagy appears to play a protective role in septic animals.

[Treatment strategy for multiple colorectal liver metastases: role for two-stage hepatectomy].

Hepatic resection is recognized as a potentially curative treatment for colorectal liver metastases. Recent progress in chemotherapy and molecular target agents has made initially unresectable colorectal liver metastases converted to resectable and may prolong survival. The definition of unresectable colorectal liver metastases was because of the lack of the future remnant liver volume due to multiple bilobar metastases. The two-stage hepatectomy combined with portal vein embolization may contribute to treatment for such multiple bilobar metastases. We describe an advantage and adverse effect of two-stage hepatectomy on treatment for multiple bilobar colorectal liver metastases.

Fibroblast growth factor 19 expression correlates with tumor progression and poorer prognosis of hepatocellular carcinoma.

BACKGROUND: Although fibroblast growth factor 19 (FGF19) can promote liver carcinogenesis in mice, its involvement in human hepatocellular carcinoma (HCC) has not been well investigated. FGF19, a member of the FGF family, has unique specificity for its receptor FGFR4. This study aimed to clarify the involvement of FGF19 in the development of HCC. METHODS: We investigated human FGF19 and FGFR4 expression in 40 hepatocellular carcinoma specimens using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) analysis and immunohistochemistry. Moreover, we examined the expression and the distribution of FGF19 and FGFR4 in 5 hepatocellular carcinoma cell lines (HepG2, HuH7, HLE, HLF, and JHH7) using RT-PCR and immunohistochemistry. To test the role of the FGF19/FGFR4 system in tumor progression, we used recombinant FGF19 protein and small interfering RNA (siRNA) of FGF19 and FGFR4 to regulate their concentrations. RESULTS: We found that FGF19 was significantly overexpressed in HCCs as compared with corresponding noncancerous liver tissue (P < 0.05). Univariate and multivariate analyses revealed that the tumor FGF19 mRNA expression was an independent prognostic factor for overall and disease-free survival. Moreover, we found that the FGF19 recombinant protein could increase the proliferation (P < 0.01, n = 12) and invasion (P < 0.01, n = 6) capabilities of human hepatocellular carcinoma cell lines and inhibited their apoptosis (P < 0.01, n = 12). Inversely, decreasing FGF19 and FGFR4 expression by siRNA significantly inhibited proliferation and increased apoptosis in JHH7 cells (P < 0.01, n = 12). The postoperative serum FGF19 levels in HCC patients was significantly lower than the preoperative levels (P < 0.01, n = 29). CONCLUSIONS: FGF19 is critically involved in the development of HCCs. Targeting FGF19 inhibition is an attractive potential therapeutic strategy for HCC.

Akt/mTOR signaling pathway is crucial for gemcitabine resistance induced by Annexin II in pancreatic cancer cells.

BACKGROUND: Although gemcitabine has been widely used as a first-line chemo reagent for patients with pancreatic cancer, the response rate remains low. We previously identified Annexin II as a factor involved in gemcitabine resistance against pancreatic cancer. The aims of this study were to elucidate the signaling mechanism by which Annexin II induces gemcitabine resistance and to develop a new therapy that overcomes the resistance against gemcitabine. METHODS: We compared the specific profiles of 12 targeted phosphorylated (p-) signaling proteins in gemcitabine-resistant (GEM-) and its wild-type pancreatic cancer cell lines (MIA PaCa-2) using the Bio-Plex assay system. We also evaluated the expression levels of Annexin II and two phosphoproteins, which showed different expressions in these two cell lines, by immunohistochemistry. RESULTS: Annexin II overexpression was significantly associated with rapid recurrence after gemcitabine-adjuvant chemotherapy in patients with resected pancreatic cancer (P < 0.05). Bio-Plex analysis showed up-regulation of p-Akt in GEM-MIA PaCa-2 cells in which Annexin II is highly expressed. The expression level of p-Akt was significantly correlated with that of the downstream protein, p-mTOR, in pancreatic cancer tissues. Inhibition of mTOR phosphorylation canceled gemcitabine resistance in GEM-MIA PaCa-2 cells. CONCLUSIONS: The Akt/mTOR pathway is involved in mechanisms of gemcitabine resistance induced by Annexin II in pancreatic cancer cells. This indicates that combination therapy with the mTOR inhibitor may overcome gemcitabine resistance. Annexin II as an indicator for selection of gemcitabine resistance could thus be applied to the development of novel tailor-made approaches for pancreatic cancer treatment.

Intrahepatic cholangiojejunostomy (Longmire procedure) for recurrent bilioenteric anastomotic stricture with hepatolithiasis.

Interventional procedure via percutaneous transhepatic route is often performed, as an initial treatment, in patients with benign bilioenteric anastomotic stricture. However, surgical management is required in most cases in which radiological intervention is unsuccessful. In this report, we describe a case of a 67-year-old woman with recurrent bilioenteric anastomotic stricture, accompanying bilateral hepatolitiasis after several times of transhepatic interventions. The patient underwent intrahepatic cholangiojejunostomy (Longmire procedure) and cholangioscopic lithotomy after resection of an atrophic left lateral segment resulting from hepatolithiasis. Although the damaged hilar bile duct had to be isolated and divided from the corresponding vasculature for re-anastomosis, it was quite impossible due to severe inflammatory change at the hepatic hilus. We, therefore, anastomosed the intact biliary stump on the cut surface of the left lateral segment to the jejunal loop with a stent tube. The patient's postoperative course was uneventful and she exhibited no evidence of cholangitis during follow-up period of 1 year after surgery. At present, the indications for intrahepatic cholangiojejunostomy for biliary obstruction, are quite limited, but biliary surgeons should keep this procedure in mind at the time of biliary reconstruction for benign proximal bile duct stricture, particularly in cases of multiply operated hilum.

[A case of pancreaticoduodenectomy for duodenal carcinoma with a replaced common hepatic artery running through the pancreatic parenchyma].

To perform safe and radical pancreaticoduodenectomy, adequate knowledge of the branching and running course of the common hepatic artery is necessary. Formation of a common trunk by the common hepatic artery and superior mesenteric artery, called the hepatomesenteric trunk, is very rare. When it occurs, the common hepatic artery arising from the hepatomesenteric trunk usually runs behind the pancreas head. In the present case, however, it ran through the pancreatic parenchyma. Therefore, pancreaticoduodenectomy for duodenal carcinoma was performed with preservation of the intrapancreatic common hepatic artery. When pancreaticoduodenectomy is performed in patients with a replaced common hepatic artery running through the pancreatic parenchyma, it is necessary to preoperatively determine whether to preserve or resect the common hepatic artery in the pancreas with consideration of the curability. If resected, whether to reconstruct it must also be determined. If reconstructed, the reconstruction method must be determined, and if not, it is important to perform preoperative coiling of the common hepatic artery and intraoperative measurement of the hepatic blood flow with a Doppler flow meter.

Usefulness of preoperative partial splenic embolization in hepatocellular carcinoma and hypersplenic thrombocytopenia.

BACKGROUND/AIMS: Patients with both hepatocellular carcinoma and hypersplenic thrombocytopenia are occasionally seen and this condition can severely complicate liver resection. This study evaluated the usefulness of preoperative partial splenic embolization (PSE) as an alternative to splenectomy (SP). METHODOLOGY: Twenty-eight patients with hypersplenic thrombocytopenia underwent hepatectomy for hepatocellular carcinoma. Five patients underwent preoperative PSE and 23 patients underwent concomitant splenectomy. The blood cell counts, laboratory chemistry data, and operative morbidity, prognosis were all examined. RESULTS: There were no severe PSE-related complications such as splenic abscess seen after PSE. The platelet counts in the PSE group significantly increased in comparison to those in the SP group before the operation. The frequency of blood transfusion and postoperative complications in the PSE group was significantly less than that in the SP group. The duration of surgery, blood loss, and performance of PSE were significant factors to predict postoperative complications. The overall survival after liver resection was not significantly different between patients in the PSE and SP group. CONCLUSIONS: Preoperative PSE could be safely performed without severe adverse effects prior to liver resection and it was thus considered to be useful for increasing the number of platelets and reducing postoperative complications.

[A successful treatment of conversion chemotherapy by mFOLFOX6 plus cetuximab for initially unresectable synchronous colorectal liver metastases].

A 63-year-old woman with a synchronous huge colorectal liver metastasis was referred to our institution.The lesion was technically diagnosed unresectable because the estimated future remnant liver volume was insufficient due to the invasion of the three hepatic veins and hepatic hilum.She underwent 7 courses of mFOLFOX6 and 14 administrations of cetuximab as conversion chemotherapy.Periodic abdominal CT scans revealed the tumor becoming PR, and she was free of cancer invasion to the left hepatic vein.After the remainder of chemotherapy lasting 4 weeks, right trisectionectomy and combined partial resection of the inferior vena cava and primary closure was performed.The postoperative course was uneventful and the patient was discharged at 20 days after the operation.She underwent chemotherapy postoperatively, and then underwent laparoscopic sigmoidectomy.A conversion chemotherapy using cetuximab may contribute to ward rapidly reducing tumor size and improving the resectability of initially unresectable huge colorectal liver metastases, thus leading to prolonged survival.

Aggressive surgical resection for hilar cholangiocarcinoma of the left-side predominance: radicality and safety of left-sided hepatectomy.

OBJECTIVES: To evaluate the clinicopathologic outcomes in patients with hilar cholangiocarcinoma (HC) after left-sided hepatectomy (L-H). SUMMARY BACKGROUND DATA: L-H is indicated as radical surgery for HC, predominantly involving left hepatic duct. However, several reports have demonstrated that L-H often results in tumor-positive margin and unfavorable prognosis compared with right-sided hepatectomy (R-H). METHODS: A total of 224 patients with HC underwent surgical resection with curative intent at our institution: L-H for Bismuth-Corlette (B-C) type IIIb tumors in 88 patients (39.3%) including 75 left hemihepatectomies and 13 left trisectionectomies, and R-H mainly for B-C type IIIa and IV tumors in 84 patients (37.5%). In this study, clinicopathologic outcomes and perioperative morbidity and mortality rates after L-H were investigated and compared with those after R-H. RESULTS: Histologically negative margin (R0) resection was achieved in 56 cases (63.6%) with L-H, similar to the results for R-H (58/84, 69.1%). However, the R0 resection rate in L-H cases with portal vein (PV) resection was lower (11/25, 44.0%), and various types of PV reconstruction were required. Proximal ductal stumps and excisional surface at periductal structures were the most common sites of positive margins. However, when curative resection was achieved, 5-year survival was comparable to that in R-H cases. Furthermore, lower mortality was noted in L-H cases, even with left trisectionectomy. Multivariate analysis indicated curability and hepatic artery resection as independent prognostic factors. CONCLUSIONS: Since L-H is a safe procedure and represents the only curative resectional option for type IIIb tumor, aggressive surgical resection should be performed even in cases with PV involvement, if R0 resection is possible.